Blackwell’s  
Five-Minute  
Veterinary  
Consult:  
Canine and Feline
Seventh Edition

books/Blackwell's _Five-Minute Veterinary Consul  Canine and Feline, 7th Edition (VetBooks.ir).pdf

Canine and Feline
Edited by
Larry P. Tilley, DVM
Diplomate, American College of Veterinary Internal Medicine
(Small Animal Internal Medicine)
President, VetMed Consultants, Inc.
Santa Fe, New Mexico
USA
Francis W.K. Smith, Jr., DVM
(Small Animal Internal Medicine and Cardiology)
Vice-President, VetMed Consultant, Inc.
Lexington, Massachusetts
USA
Meg M. Sleeper, VMD
(Cardiology)
Professor of Clinical Cardiology
College of Veterinary Medicine
University of Florida, Florida
USA
Benjamin M. Brainard, VMD
Diplomate, American College of Veterinary 
Anesthesia and Analgesia and 
American College of Veterinary Emergency and  
Critical Care 
Edward H. Gunst
Professor of Small Animal Critical Care
University of Georgia
Athens, Georgia
USA

This edition first published 2021 © 2021 by John Wiley & Sons, Inc. 
Edition History 
First Edition 1997 © Lippincott Williams & Wilkins
Second Edition 2000 © Lippincott Williams & Wilkins
Third edition 2004 © Lippincott Williams & Wilkins
Fourth Edition 2007 © Blackwell Publishing Professional
Fifth edition 2011 © John Wiley & Sons, Inc. 
Sixth Edition 2016 © John Wiley & Sons, Inc. 
All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, 
photocopying, recording or otherwise, except as permitted by law. Advice on how to obtain permission to reuse material from this title is available at http://www.wiley.
com/go/permissions.
Blackwell Publishing was acquired by John Wiley & Sons in February 2007. Blackwell’s publishing program has been merged with Wiley’s global Scientific, Technical 
and Medical business to form Wiley-Blackwell.
The right of Larry P Tilley, Francis W Smith, Meg Sleeper, and Benjamin Brainard to be identified as the authors of the editorial material in this work has been 
asserted in accordance with law.
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The contents of this work are intended to further general scientific research, understanding, and discussion only and are not intended and should not be relied upon as 
recommending or promoting scientific method, diagnosis, or treatment by physicians for any particular patient. In view of ongoing research, equipment modifications, 
changes in governmental regulations, and the constant flow of information relating to the use of medicines, equipment, and devices, the reader is urged to review and 
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Library of Congress Cataloging-in-Publication Data
Names: Tilley, Lawrence P ., editor. | Smith, Francis W. K., Jr., editor. | 
 Sleeper, Meg M., editor. | Brainard, Benjamin, editor.  
Title: Blackwell’s five-minute veterinary consult. Canine and feline / 
 edited by Larry P . Tilley, Francis W.K. Smith, Jr., Margaret M. Sleeper, 
 Benjamin Brainard.  
Other titles: Five-minute veterinary consult. Canine and feline  
Description: Seventh edition. | Hoboken, NJ : Wiley-Blackwell, 2021. | 
 Includes bibliographical references and index. 
Identifiers: LCCN 2020025494 (print) | LCCN 2020025495 (ebook) | ISBN 
 9781119513179 (hardback) | ISBN 9781119513155 (adobe pdf) | ISBN 
 9781119513162 (epub)  
Subjects: MESH: Dog Diseases–diagnosis | Cat Diseases–diagnosis | Dog 
 Diseases–therapy | Cat Diseases–therapy | Veterinary Medicine–methods 
 | Handbook 
Classification: LCC SF991  (print) | LCC SF991  (ebook) | NLM SF 991  | DDC 
 636.7/0896–dc23 
LC record available at https://lccn.loc.gov/2020025494
LC ebook record available at https://lccn.loc.gov/2020025495
Cover Design: Wiley
Cover Image: School children (8-9) at lunch break © Tetra Images - Jamie Grill / Getty Images, Playing Together at School © FatCamera / Getty Images,  
Multi-ethnic children at autumn festival © kali9 / Getty Images, WMM - Teenagers hanging out, eating popcorn in urban park © Hero Images / Getty Images
Set in 9/10pt AdobeGarmondPro by SPi Global, Pondicherry, India
10 9 8 7 6 5 4 3 2 1

To my love and joy in life, Ellen Lefkowitz, my son Kyle, and grandson T ucker.
To my late mother Dorothy, who instilled values that have helped me throughout life.
To family and animals who represent the purity of life.
Larry P . Tilley
To my wife, May, my son, Ben, and my daughter, Jade, who are a constant source of 
inspiration, love, and joy. To my late father, Frank, who was my perfect role model. To Kaylee 
(dog) and Centie (cat) who remind me each day to make time for play.
Francis W.K. Smith, Jr.
To my parents and sister for their stalwart support and to the many animals who have 
touched my life and made me a better person.
Meg M. Sleeper
To my family, my mentors, my colleagues; to colleagues and friends who are no longer with 
us. “Keep cool, but care”—Thomas Pynchon.
Benjamin M. Brainard

ix5-Fluorouracil (5-FU) Toxicosis  1
Abortion, Spontaneous (Early Pregnancy Loss)—Cats  2
Abortion, Spontaneous (Early Pregnancy Loss)—Dogs  4
Abortion, Termination of Pregnancy  6
Abscessation  8
Acetaminophen (APAP) Toxicosis  10
Acidosis, Metabolic  12
Acne—Cats  14
Acne—Dogs  15
Acral Lick Dermatitis  16
Actinomycosis and Nocardia  17
Acute Abdomen  18
Acute Diarrhea  21
Acute Kidney Injury  23
Acute Respiratory Distress Syndrome  25
Acute Vomiting  27
Adenocarcinoma, Anal Sac  29
Adenocarcinoma, Lung  31
Adenocarcinoma, Nasal  32
Adenocarcinoma, Pancreas  34
Adenocarcinoma, Prostate  35
Adenocarcinoma, Renal  36
Adenocarcinoma, Salivary Gland  37
Adenocarcinoma, Skin (Sweat Gland, Sebaceous)  38
Adenocarcinoma, Stomach, Small and Large Intestine, Rectal  39
Adenocarcinoma, Thyroid—Dogs  40
Aggression—Between Dogs in the Household  42
Aggression to Unfamiliar People and Unfamiliar Dogs—Dogs  44
Aggression Toward Children—Dogs  46
Aggression Toward Familiar People—Dogs  47
Aggression Toward Humans—Cats  49
Aggression, Food and Resource Guarding—Dogs  51
Aggression, Intercat Aggression  53
Aggression, Overview—Cats  56
Aggression, Overview—Dogs  58
Alkaline Hyperphosphatasemia in Dogs  61Contents
Topic
331 client education handouts are available at www.fiveminutevet.com/canineandfeline7th 
for you to download and use in practice

x
331 client education handouts are available at www.fiveminutevet.com/canineandfeline7th for  
you to download and use in practiceAlkalosis, Metabolic  63
Alopecia—Cats  65
Alopecia—Dogs  67
Alopecia, Noninflammatory—Dogs  69
Ameloblastoma  71
Amphetamine and ADD/ADHD Medication Toxicosis  72
Amyloidosis  74
Anaerobic Infections  76
Anal Sac Disorders  77
Anaphylaxis  78
Anemia of Chronic Kidney Disease  80
Anemia, Aplastic  82
Anemia, Heinz Body  83
Anemia, Immune-Mediated  84
Anemia, Iron-Deficiency  86
Anemia, Nonregenerative  87
Anemia, Nuclear Maturation Defects (Anemia, Megaloblastic)  89
Anemia, Regenerative  90
Anisocoria  92
Anorexia  94
Antebrachial Growth Deformities  96
Anterior Uveitis—Cats  98
Anterior Uveitis—Dogs  100
Antidepressant Toxicosis—SSRIs and SNRIs  102
Antidepressant Toxicosis—Tricyclic  104
Aortic Stenosis  106
Aortic Thromboembolism  108
Apudoma  111
Arteriovenous Fistula and Arteriovenous Malformation  112
Arteriovenous Malformation of the Liver  113
Arthritis (Osteoarthritis)  115
Arthritis, Septic  118
Ascites  120
Aspergillosis, Disseminated Invasive  122
Aspergillosis, Nasal  124
Aspirin Toxicosis  126
Asthma, Bronchitis—Cats  127
Astrocytoma  129
Ataxia  130
Atlantoaxial Instability  132
Atopic Dermatitis  134
Atrial Fibrillation and Atrial Flutter  136
Atrial Premature Complexes  139
Atrial Septal Defect  141
Atrial Standstill  142
Atrial Wall Tear  144

xi
for you to download and use in practiceAtrioventricular Block, Complete (Third Degree)  146
Atrioventricular Block, First Degree  148
Atrioventricular Block, Second Degree—Mobitz Type I  150
Atrioventricular Block, Second Degree—Mobitz Type II  152
Atrioventricular Valve Dysplasia  154
Atrioventricular Valvular Stenosis  156
Azotemia and Uremia  159
Babesiosis  161
Baclofen Toxicosis  163
Bartonellosis  164
Basal Cell Tumor  165
Battery Toxicosis  166
Baylisascariasis  167
Benign Prostatic Hyperplasia  168
Benzodiazepine and Other Sleep Aids Toxicosis  169
Beta Receptor Antagonist (Beta Blockers) Toxicosis  171
Beta-2 Agonist Inhaler Toxicosis  172
Bile Duct Carcinoma  173
Bile Duct Obstruction (Extrahepatic)  174
Bile Peritonitis  177
Bilious Vomiting Syndrome  179
Blastomycosis  180
Blepharitis  182
Blind Quiet Eye  184
Blood Transfusion Reactions  186
Blue‐Green Algae Toxicosis  187
Botulism  188
Brachial Plexus Avulsion  189
Brachycephalic Airway Syndrome  190
Brain Injury  192
Brain Tumors  194
Breeding, Timing  196
Bronchiectasis  198
Bronchitis, Chronic  200
Brucellosis  202
Calcipotriene/Calcipotriol Toxicosis  204
Calcium Channel Blocker Toxicosis  205
Campylobacteriosis  206
Candidiasis  207
Canine Coronavirus Infections  208
Canine Degenerative Myelopathy  209
Canine Distemper  211
Canine Infectious Diarrhea  213
Canine Infectious Respiratory Disease  215
Canine Parvovirus  217
Canine Schistosomiasis (Heterobilharziasis)  219

xii
you to download and use in practiceCar Ride Anxiety—Dogs and Cats  220
Carbon Monoxide Toxicosis  223
Carcinoid and Carcinoid Syndrome  224
Cardiac Glycoside Plant Toxicosis  225
Cardiomyopathy, Arrhythmogenic Right Ventricular—Cats  226
Cardiomyopathy, Arrhythmogenic Right Ventricular—Dogs  227
Cardiomyopathy, Dilated—Cats  229
Cardiomyopathy, Dilated—Dogs  232
Cardiomyopathy, Hypertrophic—Cats  235
Cardiomyopathy, Hypertrophic—Dogs  238
Cardiomyopathy, Nutritional  239
Cardiomyopathy, Restrictive—Cats  241
Cardiopulmonary Arrest  243
Cataracts  245
Cerebellar Degeneration  247
Cerebellar Hypoplasia  248
Cerebrovascular Accidents  249
Ceruminous Gland Adenocarcinoma, Ear  251
Cervical Spondylomyelopathy (Wobbler Syndrome)  252
Chagas Disease (American Trypanosomiasis)  254
Chediak-Higashi Syndrome  255
Chemodectoma  256
Cheyletiellosis  257
Chlamydiosis—Cats  258
Chocolate Toxicosis  260
Cholangitis/Cholangiohepatitis Syndrome  262
Cholecystitis and Choledochitis  265
Cholelithiasis  267
Chondrosarcoma, Bone  269
Chondrosarcoma, Nasal and Paranasal Sinus  270
Chondrosarcoma, Oral  271
Chorioretinitis  272
Chronic Kidney Disease  274
Chylothorax  277
Cirrhosis and Fibrosis of the Liver  279
Claw and Clawfold Disorders  282
Clostridial Enterotoxicosis  284
Coagulation Factor Deficiency  286
Coagulopathy of Liver Disease  288
Cobalamin Deficiency  290
Coccidioidomycosis  292
Coccidiosis  294
Cognitive Dysfunction Syndrome  295
Cold Agglutinin Disease  297
Colibacillosis  298
Colitis and Proctitis  300

xiii
for you to download and use in practiceColitis, Histiocytic Ulcerative  303
Compulsive Disorders—Cats  304
Compulsive Disorders—Dogs  306
Congenital and Developmental Renal Diseases  308
Congenital Ocular Anomalies  310
Congenital Spinal and Vertebral Malformations  313
Congestive Heart Failure, Left-Sided  315
Congestive Heart Failure, Right-Sided  317
Conjunctivitis—Cats  319
Conjunctivitis—Dogs  321
Constipation and Obstipation  323
Contact Dermatitis  325
Coonhound Paralysis (Acute Polyradiculoneuritis)  326
Copper Associated Hepatopathy  328
Coprophagia and Pica  332
Corneal and Scleral Lacerations  334
Corneal Opacities—Degenerations and Infiltrates  336
Corneal Opacities—Dystrophies  337
Corneal Sequestrum—Cats  338
Cough  339
Craniomandibular Osteopathy  341
Cruciate Ligament Disease, Cranial  342
Cryptococcosis  344
Cryptorchidism  346
Cryptosporidiosis  347
Crystalluria  348
Cutaneous Drug Eruptions  350
Cuterebriasis  351
Cyanosis  352
Cyclic Hematopoiesis  354
Cylindruria  355
Cytauxzoonosis  356
Deafness  357
Deciduous Teeth, Persistent (Retained)  359
Deep Cutaneous Mycoses  360
Demodicosis  362
Dental Caries  364
Dentigerous Cyst  366
Dermatomyositis  367
Dermatophilosis  369
Dermatophytosis  370
Dermatoses, Depigmenting Disorders  372
Dermatoses, Erosive or Ulcerative  374
Dermatoses, Exfoliative  376
Dermatoses, Neoplastic  378
Dermatoses, Papulonodular  380

xiv
you to download and use in practiceDermatoses, Sterile Nodular/Granulomatous  382
Dermatoses, Sun-Induced  384
Dermatoses, Vesiculopustular  385
Dermatoses, Viral (Non-Papillomatosis)  387
Destructive and Scratching Behavior—Cats  388
Destructive Behavior—Dogs  389
Diabetes Insipidus  391
Diabetes Mellitus With Hyperosmolar Hyperglycemic State  393
Diabetes Mellitus With Ketoacidosis  395
Diabetes Mellitus Without Complication—Cats  397
Diabetes Mellitus Without Complication—Dogs  399
Diaphragmatic Hernia  401
Diarrhea, Antibiotic Responsive  402
Diarrhea, Chronic—Cats  403
Diarrhea, Chronic—Dogs  405
Digoxin Toxicity  407
Diisocyanate Glues  408
Discolored Tooth/Teeth  409
Discospondylitis  411
Disseminated Intravascular Coagulation  413
Drowning (Near Drowning)  415
Ductal Plate Malformation (Congenital Hepatic Fibrosis)  416
Dysautonomia (Key-Gaskell Syndrome)  419
Dyschezia and Hematochezia  420
Dysphagia  422
Dyspnea and Respiratory Distress  425
Dystocia  428
Dysuria, Pollakiuria, and Stranguria  430
Ear Mites  432
Eclampsia  433
Ectopic Ureter  434
Ectropion  435
Ehrlichiosis and Anaplasmosis  436
Elbow Dysplasia  438
Electric Cord Injury  440
Enamel Hypoplasia/Hypocalcification  441
Encephalitis  442
Encephalitis Secondary to Parasitic Migration  444
Endocarditis, Infective  445
Endomyocardial Diseases—Cats  447
Entropion  449
Eosinophilia  450
Eosinophilic Granuloma Complex  451
Epididymitis/Orchitis  453
Epilepsy, Genetic (Idiopathic)—Dogs  454
Epiphora  456

xv
for you to download and use in practiceEpiscleritis  458
Epistaxis  459
Erythrocytosis  462
Esophageal Diverticula  464
Esophageal Foreign Bodies  465
Esophageal Stricture  467
Esophagitis  469
Essential Oils Toxicosis  472
Ethanol Toxicosis  473
Ethylene Glycol Toxicosis  474
Excessive Vocalization and Waking at Night—Dogs and Cats  476
Exercise-Induced Weakness/Collapse in Labrador Retrievers  478
Exocrine Pancreatic Insufficiency  480
Eyelash Disorders (Trichiasis/Distichiasis/Ectopic Cilia)  482
Facial Nerve Paresis and Paralysis  483
False Pregnancy  485
Familial Shar-Pei Fever  487
Fanconi Syndrome  489
Fear and Aggression in Veterinary Visits—Cats  490
Fear and Aggression in Veterinary Visits—Dogs  492
Fears, Phobias, and Anxieties—Cats  494
Fears, Phobias, and Anxieties—Dogs  496
Feline Alveolar Osteitis  498
Feline Calicivirus Infection  499
Feline Herpesvirus Infection  501
Feline Hyperesthesia Syndrome  503
Feline Idiopathic Lower Urinary Tract Disease  504
Feline Immunodeficiency Virus (FIV) Infection  506
Feline Infectious Diarrhea  508
Feline Infectious Peritonitis (FIP)  510
Feline Ischemic Encephalopathy  512
Feline Leukemia Virus (FeLV) Infection  514
Feline Panleukopenia  516
Feline Paraneoplastic Alopecia  518
Feline Stomatitis—Feline Chronic Gingivostomatitis (FCGS)  519
Feline Symmetrical Alopecia  521
Feline Tooth Resorption (Odontoclastic Resorption)  522
Feline (Upper) Respiratory Infections  524
Fever  526
Fiber-Responsive Large Bowel Diarrhea  528
Fibrocartilaginous Embolic Myelopathy  530
Fibrosarcoma, Bone  532
Fibrosarcoma, Gingiva  533
Fibrosarcoma, Nasal and Paranasal Sinus  534
Fipronil Toxicosis  535
Flatulence  536

xvi
you to download and use in practiceFlea Bite Hypersensitivity and Flea Control  538
Food Reactions, Dermatologic  540
Food Reactions (Gastrointestinal), Adverse  542
Gallbladder Mucocele  544
Gastric Dilation and Volvulus Syndrome  546
Gastric Motility Disorders  548
Gastritis, Chronic  550
Gastroduodenal Ulceration/Erosion  552
Gastroenteritis, Acute Hemorrhagic Diarrhea Syndrome  554
Gastroenteritis, Eosinophilic  556
Gastroesophageal Reflux  558
Gastrointestinal Obstruction  559
Gestational Diabetes Mellitus  561
Giardiasis  562
Gingival Enlargement/Hyperplasia  563
Glaucoma  564
Glomerulonephritis  566
Glucagonoma  568
Glucosuria  570
Gluten Enteropathy in Irish Setters  572
Glycogen Storage Disease  573
Glycogen-Type Vacuolar Hepatopathy  574
Grape and Raisin Toxicosis  577
Hair Follicle Tumors  578
Halitosis  579
Head Pressing  581
Head Tilt  583
Head Tremors (Bobbing), Idiopathic—Dogs  585
Heartworm Disease—Cats  586
Heartworm Disease—Dogs  587
Heat Stroke and Hyperthermia  589
Helicobacter  spp.  591
Hemangiopericytoma  593
Hemangiosarcoma, Bone  594
Hemangiosarcoma, Heart  595
Hemangiosarcoma, Skin  596
Hemangiosarcoma, Spleen and Liver  598
Hematemesis  600
Hematuria  602
Hemoglobinuria and Myoglobinuria  604
Hemothorax  606
Hemotropic Mycoplasmosis  607
Hepatic Amyloid  609
Hepatic Encephalopathy  611
Hepatic Failure, Acute  614
Hepatic Lipidosis  617

xvii
for you to download and use in practiceHepatic Nodular Hyperplasia and Dysplastic Hyperplasia  620
Hepatitis, Chronic  622
Hepatitis, Granulomatous  626
Hepatitis, Infectious (Viral) Canine  628
Hepatitis, Suppurative and Hepatic Abscess  630
Hepatocellular Adenoma  632
Hepatocellular Carcinoma  633
Hepatocutaneous Syndrome  634
Hepatomegaly  636
Hepatoportal Microvascular Dysplasia  639
Hepatosupportive Therapies  642
Hepatotoxins  643
Hepatozoonosis  645
Hiatal Hernia  646
Hip Dysplasia  647
Histiocytic Diseases—Dogs and Cats  650
Histiocytosis, Cutaneous  652
Histoplasmosis  653
Hookworms (Ancylostomiasis)  655
Horner’s Syndrome  656
Housesoiling—Cats  657
Housesoiling—Dogs  661
Hydrocephalus  663
Hydronephrosis  665
Hyperadrenocorticism (Cushing’s Syndrome)—Cats  667
Hyperadrenocorticism (Cushing’s Syndrome)—Dogs  668
Hypercalcemia  672
Hypercapnia  674
Hyperchloremia  676
Hypercoagulability  677
Hypereosinophilic Syndrome (HES)  678
Hyperestrogenism (Estrogen Toxicity)  679
Hyperglycemia  681
Hyperkalemia  683
Hyperlipidemia  685
Hypermagnesemia  687
Hypermetria and Dysmetria  689
Hypernatremia  691
Hyperosmolarity  692
Hyperparathyroidism  694
Hyperparathyroidism, Renal Secondary  696
Hyperphosphatemia  698
Hypersomatotropism/Acromegaly in Cats  700
Hypertension, Portal  701
Hypertension, Pulmonary  704
Hypertension, Systemic Arterial  706

xviii
you to download and use in practiceHyperthyroidism  709
Hypertrophic Osteodystrophy  711
Hypertrophic Osteopathy  713
Hypertrophic Pyloric Gastropathy, Chronic  714
Hyperviscosity Syndrome  716
Hyphema  717
Hypoadrenocorticism (Addison’s Disease)  719
Hypoalbuminemia  722
Hypocalcemia  724
Hypochloremia  726
Hypoglycemia  727
Hypokalemia  729
Hypomagnesemia  731
Hypomyelination  733
Hyponatremia  734
Hypoparathyroidism  736
Hypophosphatemia  739
Hypopituitarism  741
Hypopyon and Lipid Flare  742
Hyporexia  743
Hyposthenuria  744
Hypothermia  745
Hypothyroidism  747
Hypoxemia  750
Icterus  752
Idioventricular Rhythm  754
Ileus  756
Illicit/Club Drug Toxicosis  758
Imidazoline Toxicosis  759
Immunodeficiency Disorders, Primary  760
Immunoproliferative Enteropathy of Basenjis  762
Incontinence, Fecal  763
Incontinence, Urinary  765
Infertility, Female—Dogs  767
Infertility, Male—Dogs  769
Inflammatory Bowel Disease  771
Influenza  773
Insoluble Oxalate Plant Toxicosis  775
Insulinoma  776
Interstitial Cell Tumor, Testicle  779
Intervertebral Disc Disease—Cats  780
Intervertebral Disc Disease, Cervical  781
Intervertebral Disc Disease, Thoracolumbar  784
Intussusception  788
Iris Atrophy  790
Iron Toxicosis  791

xix
for you to download and use in practiceIvermectin and Other Macrocyclic Lactones Toxicosis  792
Joint Luxations  793
Keratitis, Eosinophilic—Cats  795
Keratitis, Nonulcerative  796
Keratitis, Ulcerative  798
Keratoconjunctivitis Sicca  800
Kitten Behavior Problems  801
Kitten Socialization and Kitten Classes  803
Lactic Acidosis (Hyperlactatemia)  805
Lameness  808
Laryngeal and Tracheal Perforation  810
Laryngeal Diseases  812
Lead Toxicosis  814
Left Anterior Fascicular Block  816
Left Bundle Branch Block  818
Legg–Calvé–Perthes Disease  820
Leiomyoma, Stomach, Small and Large Intestine  822
Leiomyosarcoma, Stomach, Small and Large Intestine  823
Leishmaniosis  824
Leishmaniosis, Cutaneous  825
Lens Luxation  827
Leptospirosis  828
Leukemia, Chronic Lymphocytic  830
Leukocytosis  831
Leukoencephalomyelopathy in Rottweilers  833
Lily Toxicosis  834
Lipoma, Infiltrative  835
Liver Fluke Infestation  836
Lower Urinary Tract Infection, Bacterial  838
Lower Urinary Tract Infection, Fungal  840
Lumbosacral Stenosis and Cauda Equina Syndrome  841
Lung Lobe Torsion  843
Lupus Erythematosus, Cutaneous (Discoid)  844
Lupus Erythematosus, Systemic (SLE)  845
Lyme Borreliosis  847
Lymphangiectasia  849
Lymphadenopathy/Lymphadenitis  851
Lymphedema  853
Lymphoma—Cats  854
Lymphoma—Dogs  856
Lymphoma, Cutaneous Epitheliotropic  858
Lysosomal Storage Diseases  859
Malassezia Dermatitis  860
Malignant Fibrous Histiocytoma  861
Malocclusions—Skeletal and Dental  862

xx
you to download and use in practiceMammary Gland Hyperplasia—Cats  864
Mammary Gland Tumors—Cats  865
Mammary Gland Tumors—Dogs  867
Marijuana Toxicosis  869
Marking, Roaming, and Mounting Behavior—Cats  870
Marking, Roaming, and Mounting Behavior—Dogs  872
Mast Cell Tumors  874
Mastitis  876
Maternal Behavior Problems  877
Maxillary and Mandibular Fractures  879
Megacolon  881
Megaesophagus  883
Melanocytic Tumors, Oral  886
Melanocytic Tumors, Skin and Digit  888
Melena  889
Meningioma—Cats and Dogs  891
Meningitis/Meningoencephalitis/Meningomyelitis, Bacterial  894
Meningoencephalomyelitis, Eosinophilic  896
Meningoencephalomyelitis of Unknown Etiology (MUE)  897
Mesothelioma  899
Metabolic, Nutritional, and Endocrine Bone Disorders  900
Metaldehyde Toxicosis  902
Metformin Toxicosis  903
Methemoglobinemia  904
Metritis  906
Movement Disorders  907
Mucopolysaccharidoses  908
Multidrug-Resistant Infections  909
Multiple Myeloma  911
Murmurs, Heart  912
Muscle Rupture (Muscle Tear)  914
Mushroom Toxicoses  916
Myasthenia Gravis  920
Mycobacterial Infections  922
Mycoplasmosis  924
Mycotoxicosis—Aflatoxin  926
Mycotoxicosis—Tremorgenic Toxins  927
Myelodysplastic Syndromes  928
Myelomalacia, Spinal Cord (Ascending, Descending, Progressive)  929
Myelopathy—Paresis/Paralysis—Cats  930
Myeloproliferative Disorders  932
Myocardial Infarction  933
Myocardial Tumors  934
Myocarditis  935

xxi
for you to download and use in practiceMyoclonus  937
Myopathy—Hereditary X-linked Muscular Dystrophy  938
Myopathy—Masticatory and Extraocular Myositis  939
Myopathy, Noninflammatory—Endocrine  941
Myopathy, Noninflammatory—Hereditary Labrador Retriever  943
Myopathy, Noninflammatory—Hereditary Myotonia  944
Myopathy, Noninflammatory—Hereditary Scottie Cramp  945
Myopathy, Noninflammatory—Metabolic  946
Myopathy—Polymyositis and Dermatomositis  948
Myxedema and Myxedema Coma  950
Myxomatous Mitral Valve Disease  951
Narcolepsy and Cataplexy  954
Nasal and Nasopharyngeal Polyps  955
Nasal Dermatoses—Canine  956
Nasal Discharge  958
Nasopharyngeal Stenosis  960
Neck and Back Pain  961
Necrotizing Encephalitis  963
Neonatal Mortality and Canine Herpesvirus  964
Neonatal Resuscitation and Early Neonatal Care  966
Neonicotinoid Toxicosis  968
Neosporosis  969
Nephrolithiasis  970
Nephrotic Syndrome  972
Nephrotoxicity, Drug-Induced  974
Nerve Sheath Tumors  976
Neuroaxonal Dystrophy  977
Neutropenia  978
Nocardiosis/Actinomycosis—Cutaneous  980
Nonsteroidal Anti-Inflammatory Drug Toxicosis  981
Notoedric Mange  983
Nystagmus  984
Obesity  986
Odontogenic Tumors  988
Odontoma  990
Oliguria and Anuria  991
Ollulanus Infection  993
Ophthalmia Neonatorum  994
Opiates/Opioids Toxicosis  996
Optic Neuritis and Papilledema  998
Oral Cavity Tumors, Undifferentiated Malignant Tumors  1000
Orbital Diseases (Exophthalmos, Enophthalmos, Strabismus)  1001
Organophosphorus and Carbamate Toxicosis  1003
Oronasal Fistula  1005
Osteochondrodysplasia  1006

xxii
you to download and use in practiceOsteochondrosis  1007
Osteomyelitis  1009
Osteosarcoma  1011
Otitis Externa and Media  1013
Otitis Media and Interna  1015
Ovarian Remnant Syndrome  1017
Ovarian Tumors  1019
Ovulatory Failure  1020
Pain (Acute, Chronic, and Postoperative)  1021
Palatal Defects  1025
Pancreatitis—Cats  1027
Pancreatitis—Dogs  1029
Pancytopenia  1031
Panniculitis/Steatitis  1033
Panosteitis  1034
Panting and Tachypnea  1036
Papillomatosis  1039
Paralysis  1040
Paraneoplastic Syndromes  1042
Paraphimosis, Phimosis, and Priapism  1045
Paraproteinemia  1046
Patellar Luxation  1047
Patent Ductus Arteriosus  1049
Pectus Excavatum  1052
Pelger–Huët Anomaly  1053
Pelvic Bladder  1054
Pemphigus  1055
Perianal Fistula  1057
Pericardial Disease  1058
Perineal Hernia  1061
Periodontal Disease  1063
Peripheral Edema  1065
Perirenal Pseudocysts  1067
Peritoneopericardial Diaphragmatic Hernia  1068
Peritonitis  1069
Petechiae, Ecchymosis, Bruising  1072
Petroleum Hydrocarbon Toxicosis  1074
Pheochromocytoma  1076
Phosphofructokinase Deficiency  1078
Physalopterosis  1079
Plague  1080
Plasmacytoma, Mucocutaneous  1081
Pleural Effusion  1082
Pneumocystosis  1084
Pneumonia, Aspiration  1085
Pneumonia, Bacterial  1086

xxiii
for you to download and use in practicePneumonia, Eosinophilic  1088
Pneumonia, Fungal  1090
Pneumonia, Interstitial  1092
Pneumothorax  1094
Pododermatitis  1096
Poisoning (Intoxication) Therapy  1098
Polioencephalomyelitis—Cats  1100
Polyarthritis, Erosive, Immune-Mediated  1101
Polyarthritis, Nonerosive, Immune-Mediated, Dogs  1103
Polycystic Kidney Disease  1105
Polycythemia Vera  1106
Polyneuropathies (Peripheral Neuropathies)  1107
Polyphagia  1109
Polypoid Cystitis  1111
Polyuria and Polydipsia  1113
Portosystemic Shunting, Acquired  1115
Portosystemic Vascular Anomaly, Congenital  1118
Poxvirus Infection—Cats  1122
Pregnancy Edema in the Bitch  1123
Pregnancy Toxemia  1125
Premature Labor  1126
Prolapsed Gland of the Third Eyelid (Cherry Eye)  1127
Proptosis  1128
Prostate Disease in the Breeding Male Dog  1129
Prostatic Cysts  1131
Prostatitis and Prostatic Abscess  1132
Prostatomegaly  1134
Protein-Losing Enteropathy  1136
Proteinuria  1138
Protothecosis  1141
Pruritus  1142
Pseudoephedrine/Phenylephrine Toxicosis  1144
Pseudomacrothrombocytopenia (Inherited Macrothrombocytopenia)  1145
Ptyalism  1146
Pulmonary Contusions  1148
Pulmonary Edema, Noncardiogenic  1149
Pulmonary Thromboembolism  1151
Pulmonic Stenosis  1153
Puppy Behavior Problems  1155
Puppy Socialization and Puppy Classes  1157
Puppy Strangles (Juvenile Cellulitis)  1159
Pyelonephritis  1160
Pyoderma  1162
Pyoderma—Methicillin-Resistant  1164
Pyometra  1165
Pyothorax  1168

xxiv
you to download and use in practicePyrethrin and Pyrethroid Toxicosis  1170
Pyruvate Kinase Deficiency  1171
Pythiosis  1172
Pyuria  1174
Q Fever  1176
Quadrigeminal Cyst  1177
Rabies  1178
Rectal and Anal Prolapse  1180
Rectal Stricture  1181
Rectoanal Polyps  1182
Red Eye  1183
Regurgitation  1185
Renal Tubular Acidosis  1187
Renomegaly  1188
Respiratory Parasites  1190
Retained Placenta  1192
Retinal Degeneration  1193
Retinal Detachment  1195
Retinal Hemorrhage  1197
Rhinitis and Sinusitis  1199
Right Bundle Branch Block  1202
Rocky Mountain Spotted Fever  1204
Rodenticide Toxicosis—Anticoagulants  1206
Rodenticide Toxicosis—Bromethalin  1208
Rodenticide Toxicosis—Cholecalciferol  1209
Rodenticide Toxicosis—Phosphides  1211
Roundworms (Ascariasis)  1212
Sago Palm Toxicosis  1213
Salivary Mucocele  1214
Salmon Poisoning Disease  1216
Salmonellosis  1217
Salt Toxicosis  1219
Sarcoptic Mange  1221
Schiff–Sherrington Phenomenon  1222
Schwannoma  1223
Sebaceous Adenitis, Granulomatous  1224
Seizures (Convulsions, Status Epilepticus)—Cats  1225
Seizures (Convulsions, Status Epilepticus)—Dogs  1227
Seminoma  1230
Separation Anxiety Syndrome  1231
Sepsis and Bacteremia  1235
Sertoli Cell Tumor  1237
Sexual Development Disorders  1238
Shaker/Tremor Syndrome, Corticosteroid Responsive  1240
Shock, Cardiogenic  1241
Shock, Hypovolemic  1243

xxv
for you to download and use in practiceShock, Septic  1245
Shoulder Joint, Ligament, and Tendon Conditions  1247
Sick Sinus Syndrome  1250
Sinus Arrest and Sinoatrial Block  1252
Sinus Arrhythmia  1254
Sinus Bradycardia  1256
Sinus Tachycardia  1258
Sjögren-Like Syndrome  1260
Skin Fragility Syndrome, Feline  1261
Small Intestinal Dysbiosis  1262
Smoke Inhalation  1264
Snake Venom Toxicosis—Coral Snakes  1265
Snake Venom Toxicosis—Pit Vipers  1266
Sneezing, Reverse Sneezing, Gagging  1268
Soft Tissue Sarcoma  1270
Spermatocele/Sperm Granuloma  1272
Spermatozoal Abnormalities  1273
Spider Venom Toxicosis—Black Widow  1274
Spider Venom Toxicosis—Brown Recluse  1275
Spinal Dysraphism  1276
Splenic Torsion  1278
Splenomegaly  1279
Spondylosis Deformans  1281
Sporotrichosis  1282
Squamous Cell Carcinoma, Digit  1283
Squamous Cell Carcinoma, Ear  1284
Squamous Cell Carcinoma, Gingiva  1285
Squamous Cell Carcinoma, Lung  1286
Squamous Cell Carcinoma, Nasal and Paranasal Sinuses  1287
Squamous Cell Carcinoma, Nasal Planum  1288
Squamous Cell Carcinoma, Skin  1289
Squamous Cell Carcinoma, Tongue  1290
Squamous Cell Carcinoma, Tonsil  1291
Staphylococcal Infections  1292
Steroid-Responsive Meningitis-Arteritis—Dogs  1294
Stertor and Stridor  1295
Stomatitis and Oral Ulceration  1297
Streptococcal Infections  1299
Stupor and Coma  1300
Subarachnoid Cysts (Arachnoid Diverticulum)  1302
Subinvolution of Placental Sites  1304
Submissive and Excitement Urination—Dogs  1305
Superficial Necrolytic Dermatitis  1306
Supraventricular Tachycardia  1307
Syncope  1309
Synovial Cell Sarcoma  1311

xxvi
you to download and use in practiceSyringomyelia and Chiari-Like Malformation  1312
Systolic Anterior Motion  1315
Tapeworms (Cestodiasis)  1317
Temporomandibular Joint Disorders  1318
Testicular Degeneration and Hypoplasia  1319
Tetanus  1320
Tetralogy of Fallot  1322
Third Eyelid Protrusion  1323
Thrombocytopathies  1325
Thrombocytopenia  1327
Thrombocytopenia, Primary Immune-Mediated  1329
Thrombocytosis  1331
Thunderstorm and Noise Phobias  1333
Thymoma  1335
Tick Bite Paralysis  1336
Ticks and Tick Control  1338
Toad Venom Toxicosis  1340
Tooth—Missing  1341
Tooth Formation/Structure, Abnormal  1342
Tooth Root Abscess (Apical Abscess)  1343
Torsion of the Spermatic Cord  1345
Toxoplasmosis  1346
Tracheal Collapse  1348
Transitional Cell Carcinoma  1350
Transmissible Venereal Tumor  1352
Traumatic Dentoalveolar Injuries (TDI)  1353
Tremors  1355
Trichomoniasis  1357
Trigeminal Neuritis, Idiopathic  1358
Tularemia  1359
Unruly Behaviors: Jumping, Pulling, Chasing, Stealing—Dogs  1361
Ureterolithiasis  1363
Urethral Prolapse  1365
Urinary Retention, Functional  1366
Urinary Tract Obstruction  1368
Urinary Tract Parasites  1370
Urolithiasis, Calcium Oxalate  1372
Urolithiasis, Calcium Phosphate  1375
Urolithiasis, Cystine  1376
Urolithiasis, Pseudo (Dried Blood, Ossified Material)  1378
Urolithiasis, Struvite—Cats  1379
Urolithiasis, Struvite—Dogs  1381
Urolithiasis, Urate  1383
Urolithiasis, Xanthine  1385
Uterine Inertia  1386
Uterine Tumors  1387

xxvii
for you to download and use in practiceUveal Melanoma—Cats  1388
Uveal Melanoma—Dogs  1389
Uveodermatologic Syndrome (VKH)  1390
Vaginal Discharge  1391
Vaginal Hyperplasia and Prolapse  1393
Vaginal Malformations and Acquired Lesions  1394
Vaginal Tumors  1396
Vaginitis  1397
Vascular Ring Anomalies  1399
Vasculitis, Cutaneous  1400
Vasculitis, Systemic (Including Phlebitis)  1401
Ventricular Arrhythmias and Sudden Death in German Shepherds  1404
Ventricular Fibrillation  1405
Ventricular Pre-Excitation and Wolff–Parkinson–White Syndrome  1407
Ventricular Premature Complexes  1409
Ventricular Septal Defect  1411
Ventricular Standstill (Asystole)  1413
Ventricular Tachycardia  1415
Vertebral Column Trauma  1419
Vesicourachal Diverticula  1421
Vestibular Disease, Geriatric—Dogs  1422
Vestibular Disease, Idiopathic—Cats  1424
Vomiting, Chronic  1426
Von Willebrand Disease  1429
Weight Loss and Cachexia  1431
West Nile Virus Infection  1434
Whipworms (Trichuriasis)  1435
Xylitol Toxicosis  1436
Zinc Toxicosis  1437
Appendix I Normal Reference Ranges for Laboratory Tests  1441
Table I-A Normal hematologic values  1441
Table I-B Normal biochemical values  1441
Table I-C Conversion table for hematologic units  1442
Table I-D Conversion table for clinical biochemical units  1443
Appendix II Endocrine Testing  1444
 Table II-A Endocrine function testing protocols  1444
Table II-B Tests of the endocrine system  1445
Table II-C Conversion table for hormone assay units  1446
Appendix III Approximate Normal Ranges for Common Measurements  
in Dogs and Cats  1447
Appendix IV Normal Values for the Canine and Feline Electrocardiogram  1448
Appendix V Antidotes and Useful Drugs: Methods of Treatment  1449
Appendix VI Toxic Home and Garden Hazards for Pets  1452
Table VI-A Toxic plants and their clinical signs—antidotes and treatment  1452
Table VI-B Herbal toxicities  1457

xxviii
you to download and use in practiceTable VI-C Household cleaners, disinfectants, and solvents—products,  
clinical signs, and treatment  1460
Appendix VII Pain Management  1465
Table VII-A Recommended parenteral opioid dosages and indications  1465
Table VII-B Recommended dispensable opioid dosages and indications  1465
Table VII-C Recommended parenteral local anesthetic dosages and indications  1466
Table VII-D Recommended parenteral NSAID dosages and indications  1466
Table VII-E Recommended dispensable NSAID dosages and indications  1467
Table VII-F Dosages and indications for selected drugs used to treat  
neuropathic pain  1468
Appendix VIII Medications and Supplements for Osteoarthritis  1469
Table VIII-A Anti-inflammatories and pain medications  1469
Table VIII-B Recommended parenteral NSAID dosages and indications  1470
Table VIII-C Recommended oral NSAID dosages and indications  1471
Table VIII-D Disease-Modifying Drugs (DMOADs)  1472
Appendix IX Glossary of Terminology for Seizures and Epileptic Disorders  1473
Appendix X Common Procedures and Testing Protocols  1475
Abdominocentesis and Fluid Analysis  1476
Arthrocentesis With Synovial Fluid Analysis  1479
Bacterial Culture and Sensitivity  1483
Blood Gas Interpretation  1485
Blood Pressure Determination: Noninvasive and Invasive  1488
Blood Sample Collection  1490
Blood Smear Microscopic Examination  1492
Blood Smear Preparation  1496
Blood Typing  1498
Bone Marrow Aspirate and Biopsy  1501
Bone Marrow Aspirate Cytology: Microscopic Evaluation  1503
Complete Ophthalmologic Exam  1507
Crossmatch  1512
Cystocentesis  1514
Electrocardiography  1517
Fecal Direct Smear and Cytology  1520
Fecal Flotation  1522
Fine-Needle Aspiration  1525
Fluid Analysis  1527
Glucose Curve  1530
Impression Smear  1533
Pericardiocentesis  1534
Point of Care Abdominal Ultrasonography  1538
Point of Care Pleural Space and Lung Ultrasonography  1541
Rectal Scraping and Cytology  1547
Saline Agglutination Test  1548
Thoracocentesis and Fluid Analysis  1550
Tracheal Wash  1553
Ultrasound‐Guided Mass or Organ Aspiration  1555

xxix
for you to download and use in practiceUrethral Catheterization  1559
Urinalysis Overview  1563
Urine Sediment  1565
Appendix XI Conversion Tables  1569
Table XI-A Conversion table of weight to body surface area (in square  
meters) for dogs  1569
Table XI-B Approximate equivalents for degrees Fahrenheit and Celsius  1569
Table XI-C Weight-unit conversion factors  1570
Appendix XII Important Resources for Veterinarians  1571
Index  1573

xxxi
for you to download and use in practiceAppendices
Table VI-C Household cleaners, disinfectants, and solvents—products,  
Table VII-C Recommended parenteral local anesthetic dosages  
and indications  1466
Appendix IX Glossary of Terminology for Seizures and Epileptic Disorders  1473TopicContents by Subject

xxxii
you to download and use in practiceAppendix X Common Procedures and Testing Protocols  1475
Urethral Catheterization  1559
Behavior
Aggression—Between Dogs in the Household  42
Aggression to Unfamiliar People and Unfamiliar Dogs—Dogs  44

xxxiii
for you to download and use in practiceAggression Toward Humans—Cats  49
Car Ride Anxiety—Dogs and Cats  220
Coprophagia and Pica  332
Destructive and Scratching Behavior—Cats  388
Excessive Vocalization and Waking at Night—Dogs and Cats  476
Fear and Aggression in Veterinary Visits—Cats  490
Fear and Aggression in Veterinary Visits—Dogs  492
Fears, Phobias and Anxieties—Cats  494
Fears, Phobias and Anxieties—Dogs  496
Submissive and Excitement Urination—Dogs  1305
Cardiology
Arteriovenous Fistula and Arteriovenous Malformation  112
Atrial Fibrillation and Atrial Flutter  136
Atrioventricular Block, Complete (Third Degree)  146

xxxiv
you to download and use in practiceAtrioventricular Block, Second Degree—Mobitz Type II  152
Fever  526
Shock, Septic  1245

xxxv
for you to download and use in practiceSinus Arrest and Sinoatrial Block  1252
Tetralogy of Fallot  1322
Ventricular Arrhythmias and Sudden Death in German Shepherds  1404
Ventricular Pre-Excitation and Wolff–Parkinson–White Syndrome  1407
Dentistry
Malocclusions—Skeletal and Dental  862
Maxillary and Mandibular Fractures  879
Stomatitis and Oral Ulceration  1297
Temporomandibular Joint Disorder  1318

xxxvi
you to download and use in practiceDermatology
Claw and Clawfold Disorders  282
Dermatoses, Sterile Nodular/Granulomatous  382
Flea Bite Hypersensitivity and Flea Control  538
Lymphoma, Cutaneous Epitheliotropic   858
Otitis Externa and Media  1013

xxxvii
for you to download and use in practicePododermatitis  1096
Ticks and Tick Control  1338
Endocrinology  
and Metabolism
Carcinoid and Carcinoid Syndrome  224
Diabetes Mellitus With Hyperosmolar Hyperglycemic State  393
Diabetes Mellitus With Ketoacidosis  395
Hyperthyroidism  709

xxxviii
you to download and use in practiceHypomagnesemia  731
Myxedema and Myxedema Coma  950
Gastroenterology
Colitis and Proctitis  300
Colitis, Histiocytic Ulcerative  303
Constipation and Obstipation  323
Dyschezia and Hematochezia  420
Gastric Dilation and Volvulus Syndrome  546
Gluten Enteropathy in Irish Setters  572

xxxix
for you to download and use in practiceHematemesis  600
Ileus  756
Immunoproliferative Enteropathy of Basenjis  762
Melena  889
Rectal and Anal Prolapse  1180
Weight Loss and Cachexia  1431
Hematology/
Immunology

xl
you to download and use in practiceErythrocytosis  462
Hepatology
Alkaline Hyperphosphatasemia in Dogs  61
Arteriovenous Malformation of the Liver  113
Cirrhosis and Fibrosis of the Liver  279
Coagulopathy of Liver Disease  288

xli
for you to download and use in practiceHepatic Failure, Acute  614
Hepatic Nodular Hyperplasia and Dysplastic Hyperplasia  620
Infectious  
Diseases
Actinomycosis and Nocardia  17

xlii
you to download and use in practiceCryptosporidiosis  347
Ehrlichiosis and Anaplasmosis  436
Neonatal Mortality and Canine Herpesvirus  964
Sepsis and Bacteremia  1235

xliii
for you to download and use in practiceWest Nile Virus Infection  1434
Musculoskeletal
Metabolic, Nutritional, and Endocrine Bone Disorders  900
Osteochondrosis  1007
Shoulder Joint, Ligament, and Tendon Conditions  1247
Nephrology/ 
Urology

xliv
Anemia of Chronic Kidney Disease  80
Azotemia and Uremia  159
Congenital and Developmental Renal Diseases  308
Dysuria, Pollakiuria, and Stranguria  430
Hemoglobinuria and Myoglobinuria  604
Oliguria and Anuria  991
Polyuria and Polydipsia  1113
Prostatitis and Prostatic Abscess  1132

xlv
for you to download and use in practiceUrolithiasis, Cystine  1376
Urolithiasis, Pseudo (Dried Blood, Ossified Material)  1378
Neurology
Ataxia  130
Congenital Spinal and Vertebral Malformations  313
Encephalitis Secondary to Parasitic Migration  444
Exercise-Induced Weakness/Collapse in Labrador Retrievers  478
Facial Nerve Paresis and Paralysis  483
Hypermetria and Dysmetria  689
Leukoencephalomyelopathy in Rottweilers  833
Lumbosacral Stenosis and Cauda Equina Syndrome  841
Meningioma—Cats and Dogs  891
Meningoencephalomyelitis of Unknown Etiology (MUE)  897

xlvi
you to download and use in practiceMovement Disorders  907
Myoclonus  937
Narcolepsy and Cataplexy  954
Neck and Back Pain  961
Otitis Media and Interna  1015
Pain (Acute, Chronic, and Postoperative)  1021
Stupor and Coma  1300
Syringomyelia and Chiari-Like Malformation  1312
Oncology
Adenocarcinoma, Stomach, Small and Large Intestine, Rectal  39

xlvii
for you to download and use in practiceAstrocytoma  129
Chondrosarcoma, Nasal and Paranasal Sinus  270
Fibrosarcoma, Nasal and Paranasal Sinus  534
Hemangiosarcoma, Spleen and Liver  598
Histiocytic Diseases—Dogs and Cats  650
Leiomyoma, Stomach, Small and Large Intestine  822
Leiomyosarcoma, Stomach, Small and Large Intestine  823
Melanocytic Tumors, Skin and Digit  888

xlviii
you to download and use in practiceSertoli Cell Tumor  1237
Squamous Cell Carcinoma, Nasal and Paranasal Sinuses  1287
Ophthalmology
Anterior Uveitis—Cats    98
Corneal and Scleral Lacerations  334
Corneal Opacities—Degenerations and Infiltrates  336
Episcleritis  458
Hypopyon and Lipid Flare  742

xlix
for you to download and use in practiceKeratitis, Ulcerative  798
Optic Neuritis and Papilledema   998
Prolapsed Gland of the Third Eyelid (Cherry Eye)  1127
Uveal Melanoma—Cats  1388
Respiratory
Cough  339
Dyspnea and Respiratory Distress  425
Laryngeal and Tracheal Perforation  810
Nasal and Nasopharyngeal Polyps  955
Panting and Tachypnea  1036
Pneumonia, Eosinophilic  1088

l
you to download and use in practicePneumonia, Fungal  1090
Rhinitis and Sinusitis  1199
Stertor and Stridor  1295
Theriogenology
Abortion, Termination of Pregnancy  6
Mammary Gland Hyperplasia—Cats  864
Neonatal Resuscitation and Early Neonatal Care  966
Paraphimosis, Phimosis, and Priapism  1045
Pregnancy Edema in the Bitch  1123
Prostate Disease in the Breeding Male Dog  1129
Subinvolution of Placental Sites  1304
Testicular Degeneration and Hypoplasia  1319
Torsion of the Spermatic Cord  1345

li
for you to download and use in practiceUterine Inertia  1386
Vaginal Hyperplasia and Prolapse  1393
Vaginal Malformations and Acquired Lesions  1394
Toxicology
5-Fluorouracil (5-FU)  Toxicosis  1
Amphetamine and ADD/ADHD Medication Toxicosis   72
Antidepressant Toxicosis—SSRIs and SNRIs  102
Benzodiazepine and Other Sleep Aids Toxicosis  169
Blue-Green Algae Toxicosis  187
Grape and Raisin Toxicosis  577
Imidazoline Toxicosis   759
Ivermectin and Other Macrocyclic Lactones Toxicosis  792

lii
you to download and use in practiceOpiates/Opioids Toxicosis  996
Organophosphorus and Carbamate Toxicosis  1003
Poisoning (Intoxication) Therapy   1098
Pyrethrin and Pyrethroid Toxicosis  1170
Index  1573

liiiKeeping abreast of advances in veterinary internal medicine is extremely difficult, especially for the 
busy general practitioner. To keep current with all the veterinary journals while practicing medicine is 
impossible. The veterinarian in practice can be overwhelmed by all of the findings and conclusions of 
thousands of studies conducted by veterinary specialists. Blackwell’s Five-Minute Veterinary Consult  is 
designed to provide the busy veterinary practitioner and student of veterinary medicine with concise 
practical reviews of almost all the diseases and clinical problems in dogs and cats. Our goal in creating 
this textbook was also to provide up-to-date information in an easy-to-use format. Emphasis is placed 
on diagnosis and treatment of problems and diseases likely to be seen by veterinarians.
Our fondest dream was realized when the first six editions of this book were chosen as a comprehensive 
reference source for canine and feline medicine by veterinary students, practicing veterinarians, and 
board-certified specialists. The format has proven easy to use and very popular with busy practitioners. 
The scope of the book and the number of Consulting Editors and authors have been expanded. We 
have also increased the number of authors from outside North America, to provide the best advice in 
the world. The number of topics has been increased, and every topic has been updated to provide you 
with the most current information possible in a textbook. The appendixes have also been expanded to 
include more useful tables.
Several good veterinary internal medicine textbooks are available. The uniqueness and value of 
Blackwell’s Five-Minute Veterinary Consult  as a quick reference is the consistency of presentation, the 
breadth of coverage, the contribution of large numbers of experts, and the timely preparation of the 
manuscript. The format of every topic is identical, making it easy to find information. An extensive list 
of topic headings ensures complete coverage of each topic.
As the title implies, one objective of this book is to make information quickly available. To this end, we 
have organized topics alphabetically from A to Z. Most topics can be found without using the index. A 
table of contents broken out by organ system and a detailed index are provided. Large volumes of useful 
information are summarized in charts in the appendixes. Included in the appendixes are normal labora -
tory values, endocrine testing protocols, common procedures and testing protocols, toxicology tables, 
pain management tables, Rx for Osteoarthritis, disease-modifying drugs table, an epilepsy classification 
table, conversion tables, and other information pages with important resources for veterinarians. For 
this new edition, an appendix has been added to include common procedures and testing protocols 
used in veterinary medicine.
We are delighted and privileged to have had the assistance of numerous experts in veterinary internal 
medicine from around the world. More than 450 veterinary specialists contributed to this text, allow -
ing each chapter to be written by an expert on the subject. In addition to providing outstanding infor -
mation, this large pool of experts allowed us to publish this major text in a timely manner.
Many large textbooks take several years to write, making some of the information outdated by the time 
the book is published. We are indebted to the many contributors and Consulting Editors whose hard 
work allowed us to write, edit, and publish this work in 3 years, with most chapters completed within 
a year of publication. Our goal is to revise the text every 3–4 years, so that the contents will always be 
current.
Blackwell’s Five-Minute Veterinary Consult: Canine and Feline, Seventh Edition is available in a variety of 
digital formats. Visit  www.wiley.com/go/5MVC  for more information . This edition also includes Client 
Education Handouts based on the content of Blackwell’s Five-Minute Veterinary Consult . The compli -
mentary Client Education Handouts are available on a companion website at www.fiveminutevet.com/
canineandfeline featuring 331 Client Education Handouts for you to customize and use in practice. 
These Handouts can be edited to reflect your practice preferences and then printed on your letterhead 
to distribute to your clients.Preface

liv
The book will also be published as an e-book, in downloadable ePub/ePDF formats. Now veterinarians 
can quickly access information about necessary clinical skills and new developments in diagnosis and 
treatment on their computers or mobile versions. The electronic versions offer fast, affordable access 
to  much of the accumulated wisdom in veterinary medicine. This technology brings to the clinic 
examination room and doctor’s office an easy-to-use resource that will markedly improve the quality of 
continuing education and clinical practice, and a companion website offers client education handouts 
to be downloaded and used in practice.
The seventh edition of this textbook constitutes an important, up-to-date medical reference source for 
your practice and clinical education. We strived to make it complete yet practical and easy to use. Our 
dreams are realized if this text helps you to quickly locate and use the “momentarily important” infor -
mation that is essential to the practice of high-quality veterinary medicine. We would appreciate your 
input so that we can make future editions even more useful. If you would like to see any changes in 
content or format, additions, or deletions, please let us know. Send comments to the following:
Drs. Tilley, Smith, Sleeper and Brainard
c/o John Wiley & Sons
1606 Golden Aspen Dr Ste 104
Ames, IA 50010, USA

lvThe completion of this textbook provides a welcome opportunity to recognize in writing the many 
individuals who have helped along the way. The Editors gratefully acknowledge the Consulting Editors 
and the contributors who, by their expertise, have so unmistakably enhanced the quality of this 
textbook.
We would also like to acknowledge and thank our families for their support of this project and the 
sacrifices they made to allow us the time to complete the book.
In addition to thanking veterinarians who have referred patients to us, we would like to express our 
gratitude to all the veterinary students, interns, and residents who we have had the privilege to teach. 
Their curiosity and intellectual stimulation have enabled us to grow and have prompted us to under -
take the task of writing this book.
Finally, a special acknowledgment goes to everyone at Wiley Blackwell. The marketing and sales depart -
ments also must be acknowledged for generating such an interest in this book. They are all meticulous 
workers and kind people who have made the final stages of preparing this book both inspiring and fun. 
We would also like to thank copy-editors Sally Osborn and Harriet Stewart-Jones, and Erica Judisch, 
Executive Editor. A special thank you goes to Mirjana Misina, Editorial Project Manager, who spent 
hours and days keeping track of all the contributors and the deadline dates for manuscripts. This edi -
tion would not have taken place without her. An important life goal of ours has been fulfilled: to pro -
vide expertise in small animal internal medicine worldwide and to teach the principles contained in this 
textbook to veterinarians and students everywhere.
Larry P . Tilley, Francis W.K. Smith, Jr.,
Meg M. Sleeper and Benjamin M. BrainardAcknowledgments

lvi
 Consulting Editors
MICHAEL AHERNE, MVB, GradDipVetStud, 
MS, MANZCVS (Small Animal Surgery)
Diplomate ACVIM (Cardiology)
Clinical Assistant Professor
Department of Small Animal Clinical 
Sciences
University of Florida
Gainesville, Florida, USA
Subject: Cardiology
MELINDA S. CAMUS, DVM
Diplomate ACVP (Clinical Pathology)
Associate Professor
Department of Pathology
Athens, Georgia, USA
Subject: Hematology/Immunology
TIMOTHY M. FAN, DVM, PhD
Diplomate ACVIM (Small Animal Internal 
Medicine, Oncology)
Professor
Department of Veterinary Clinical Medicine
University of Illinois at Urbana-Champaign
Urbana, Illinois, USA
Subject: Oncology
J.D. FOSTER, VMD
Medicine)
Nephrology/Urology & Internal Medicine
Friendship Hospital for Animals
Washington, DC, USA
Subject: Nephrology
MATHIEU M. GLASSMAN, VMD
Diplomate ACVS
Chief of Surgery
Friendship Surgical Specialists
Subject: MusculoskeletalKATE HOLAN, BS, DVM
Medicine)
Assistant Professor and Head  
Small Animal Internal Medicine
Sciences
Michigan State University
East Lansing, Michigan, USA
Subject: Hepatology
L YNN R. HOVDA, RPH, DVM, MS
Diplomate ACVIM (Large Animal Internal 
Medicine)
Director of Veterinary Medicine
SafetyCall International & Pet Poison 
Helpline
Bloomington, Minnesota;
Assistant Adjunct Professor
Department of Veterinary Biomedical 
Sciences
University of Minnesota
St. Paul, Minnesota, USA
Subject: Toxicology
AMIE KOENIG, DVM
Medicine), Diplomate ACVECC
Professor of Emergency and Critical Care
Department of Small Animal Medicine and 
Surgery
Subject: Infectious Diseases
GARY M. LANDSBERG, BSc, DVM
Diplomate ACVB, ECAWBM
Veterinary Behaviourist
Vice-President
CanCog Incorporated
Fergus, Ontario;
Head
Fear Free Research
Canada
Subject: BehaviorPATTY A. LATHAN, VMD, MS
Medicine)
Department of Clinical Sciences
Mississippi State University
Mississippi State, Mississippi, USA
Subject: Endocrinology/Metabolism
HEIDI B. LOBPRISE, DVM
Diplomate AVDC (Dentistry)
Main Street Veterinary Dental Clinic
Flower Mound, Texas, USA
Subject: Dentistry
KATHERN E. MYRNA, DVM, MS
Diplomate ACVO
Associate Professor of Ophthalmology
Surgery
Subject: Ophthalmology
MARK P . RONDEAU, DVM
Medicine)
Professor of Clinical Medicine
Department of Clinical Sciences and 
Advanced Medicine
School of Veterinary Medicine
University of Pennsylvania
Philadelphia, Pennsylvania, USA
Subject: Gastroenterology
ELIZABETH ROZANSKI, DVM
Diplomate ACVECC
Diplomate DACVIM (Small Animal  
Internal Medicine)
Department of Clinical Science
Cummings School of Veterinary Medicine
Tufts University
North Grafton, Massachusetts, USA
Subject: Respiratory

lviiERIN E. RUNCAN, DVM
Diplomate ACT
Associate Professor—Clinical
Theriogenology and Reproductive Medicine
Department of Veterinary Clinical Sciences
The Ohio State University
Columbus, Ohio, USA
Subject: TheriogenologyALEXANDER H. WERNER RESNICK, VMD
Diplomate ACVD
Staff Dermatologist
Animal Dermatology Center
Studio City & Westlake Village
California, USA
Subject: DermatologyAcknowledgment
The Book Editors acknowledge the prior 
contribution of the following Consulting 
Editors:
Stephen C. Barr (Infectious Diseases)
Deborah S. Greco (Endocrinology)
Sara K. Lyle (Theriogenology)
Stanley L. Marks (Gastroenterology)
Paul E. Miller (Ophthalmology)
Joane M. Parent (Neurology)
Carl A. Osborne (Nephrology/Urology)
Alan H. Rebar (Hematology/Immunology)
Walter C. Renberg (Musculoskeletal)

lviii
 Contributors
JONATHAN A. ABBOTT, DVM
Sciences
University of Tennessee
Knoxville, Tennessee
USA
ANTHONY C.G. ABRAMS-OGG, DVM, DVSc
Medicine)
Professor
Department of Clinical Studies
University of Guelph
Ontario Veterinary College
Guelph, Ontario
Canada
LARRY G. ADAMS, DVM, PhD
Medicine)
Professor of Small Animal Internal 
Medicine
Department of Veterinary Clinical 
Sciences
Purdue University
West Lafayette, Indiana
USA
DARCY B. ADIN, DVM
Clinical Associate Professor
Department of Large Animal Clinical 
Sciences
Gainesville, Florida
USA
Sciences
USAHASAN ALBASAN, DVM, MS, PhD
Associate Veterinarian
Nephrology & Urology
Veterinary Care Specialists
Milford, Michigan
USA
RACHEL A. ALLBAUGH, DVM, MS
Diplomate ACVO (Ophthalmology)
Sciences
Iowa State University
Ames, Iowa
USA
KARIN ALLENSPACH, Dr.med.vet, PhD, 
FHEA, AGAF
Diplomate ECVIM-CA
Professor
Ames, Iowa
USA
COLLEEN M. ALMGREN, DVM, PhD
Diplomate DABT
Diplomate DABVT
Veterinary Toxicologist
Pet Poison Helpline/SafetyCall 
International
Bloomington, Minnesota
USA
SARAH R. ALPERT, DVM
Diplomate ABT
Consulting Veterinarian, Clinical Toxicology
Pet Poison Helpline & SafetyCall 
USA
SOPHIE ASCHENBROICH, DVM, PhD
Diplomate ACVP (Anatomic Pathology)
Assistant Professor
Department of Pathobiological Sciences
University of Wisconsin-Madison
Madison, Wisconsin
USAGENNA ATIEE, DVM
Medicine)
Interventional Radiology Fellow
Veterinary Medical Center
USA
MELISSA J. BAIN, DVM, MS
Diplomate ACVB (Behavior)
Diplomate ACAW (Welfare)
Professor, Clinical Animal Behavior
Department of Veterinary Medicine and 
Epidemiology
University of California, Davis
Davis, California
USA
TOMAS W. BAKER
Pound Sound Consulting
Three Rivers, California
USA
CHERYL E. BALKMAN, DVM
Senior Lecturer
Cornell University
Ithaca, New Y ork
USA
GAD BANETH, DVM, PhD
Diplomate ECVCP
Professor
Koret School of Veterinary Medicine
The Hebrew University
Rehovot
Israel
KRISTIN M. BANNON, DVM, FAVD
Diplomate AVDC
Veterinary Dentistry and Oral Surgery of 
New Mexico, LLC
Algodones, New Mexico
USA

lixRENEE BARBER, DVM, PhD
Diplomate ACVIM (Neurology)
Assistant Professor of Neurology and 
Neurosurgery
Department of Small Animal Medicine 
and Surgery
USA
LAURA A. BARBUR, DVM
Diplomate ACVS (Small Animal)
Small Animal Surgeon
Department of Surgery
Washington, DC
USA
ADRIENNE M. BARCHARD COUTS, DVM
Resident ACVECC (SA)
Westford Veterinary Emergency and 
Referral Center
Westford, Massachusetts
USA
HEIDI L. BARNES HELLER, DVM
Clinical Associate Professor, Neurology/
USA
MARGARET C. BARR, DVM, PhD
Associate Dean for Academic Affairs
Professor of Virology and Immunology
Western University of Health Sciences
Pomona, California
USA
CARLA BARSTOW, DVM, MS
Diplomate ACT (Theriogenology)
Highland Pet Hospital
Lakeland, Florida
USA
JOSEPH W. BARTGES, DVM, PhD
Medicine)
Diplomate ACVN
Professor of Medicine and Nutrition
The University of Georgia
USAKRISTEN BARTHOLOMEW, DVM
Emergency Clinician
Veterinary Referral Center
Malvern, Pennsylvania
USA
FIONA L. BATEMAN, BVSc
Assistant Professor of Dermatology
USA
REBECCA M. BATES, DVM
Cardiology Resident
USA
ADRIENNE C. BAUTISTA, DVM, PhD
Diplomate ABVT
Scientific Services Veterinarian
Royal Canin
USA
ASHLEY E. BAVA, BVetMed (Hons)
Garden State Veterinary Specialists
Tinton Falls, New Jersey
USA
SARAH S.K. BEATTY , DVM
Diplomate ACVP (Clincial Pathology)
Department of Comparative, Diagnostic, 
and
Population Medicine
USA
JAN BELLOWS, DVM
Diplomate ABVP
All Pets Dental
Weston, Florida
USAELSA BELTRAN, Ldo Vet, PGDipVetEd, 
MRCVS
Diplomate ECVN
Associate Professor in Veterinary 
Neurology & Neurosurgery
Department of Clinical Science & 
Services
The Royal Veterinary College
University of London
North Mymms
Hatfield, Herts
United Kingdom
MARIAN E. BENITEZ, DVM, MS
Diplomate ACVS-SA
Surgeon/Owner
Dogwood Veterinary Surgical Care, PLLC
Huntersville, North Carolina
USA
KIA BENSON, DVM
Associate Veterinarian, Clinical Toxicology
Helpline
USA
ELLISON BENTLEY , DVM
Clinical Professor, Comparative 
Department of Surgical Sciences
USA
ALL YSON BERENT, DVM, DACVIM
Director, Interventional Endoscopy Services
Staff Internal Medicine Specialist
Animal Medical Center
New Y ork, NY
USA
JEANNINE BERGER, DVM, CAWA
Senior VP of Rescue and Welfare
The Society for Prevention of Cruelty to 
Animals (SPCA)
San Francisco, California
USA
MATTHEW R. BERRY , DVM
Medical Oncology Resident
Medicine;
PhD Candidate
Department of Pathobiology
Urbana, Illinois
USA

lx
CHRISTINE F . BERTHELIN-BAKER, DVM
Neurologist
Atlanta, Georgia
USA
JEAN M. BETKOWSKI, VMD
Staff Cardiologist
Cape Cod Veterinary Specialists
S. Dennis, Massachusetts
USA
ADAM J. BIRKENHEUER, DVM, PhD
Diplomate ACVIM
Professor of Internal Medicine
Department of Clinical Medicine
North Carolina State University
Raleigh, North Carolina
USA
KARYN BISCHOFF , DVM, MS
Diagnostic Toxicologist
New Y ork State Animal Health Diagnostic 
Laboratory
Department of Population Medicine and 
Diagnostic Sciences
USA
MARIE-CLAUDE BLAIS, DVM
Medicine)
Faculty of Veterinary Medicine
Université de Montréal
St-Hyacinthe, Quebec
Canada
APRIL E. BLONG, DVM
Sciences
Ames, Iowa
USA
JOHN D. BONAGURA, DVM, MS
Diplomate ACVIM (Cardiology, Internal 
Medicine)
Raleigh, North Carolina;
Professor Emeritus of Veterinary Clinical 
Sciences
Columbus, Ohio
USALINDSAY BOOZER, DVM
Staff Neurologist
USA
DWIGHT D. BOWMAN, MS, PhD
Diplomate ACVM (Parasitology, Honorary)
Professor
Department of Microbiology and 
USA
SØREN BOYSEN, DVM
Professor
Veterinary Emergency and Critical Care
Department of Veterinary Clinical and 
University of Calgary
Calgary, Alberta
Canada
BENJAMIN M. BRAINARD, VMD
Diplomate ACVAA and ACVECC
Edward H. Gunst Professor of Small 
Animal Critical Care
USA
RANDI BRANNAN, DVM, FAVD
Animal Dental Clinic
Portland, Oregon
USA
MATT BREWER, DVM, PhD
Diplomate ACVM (Parasitology)
Department of Veterinary Pathology
Ames, Iowa
USA
AL YSSA J. BROOKER, DVM
Resident, Clinical Pathology
USAMARJORY B. BROOKS, DVM
Diplomate ACVIM (Small Animal)
Director
Comparative Coagulation Section, Animal 
Health Diagnostic Laboratory
USA
AHNA G. BRUTLAG, DVM, MS
Director, Veterinary Services & Senior 
Adjunct Assistant Professor
Department of Veterinary and Biomedical 
Sciences
St. Paul, Minnesota
USA
JÖRG BUCHELER, DVM, PhD, FTA
Diplomate ACVIM (IM)
Veterinary Specialty Hospital of Palm 
Beach Gardens
Palm Beach Gardens, Florida
USA
ANDREW C. BUGBEE, DVM
Medicine)
Associate Clinical Professor of IM
Department of Small Animal Medicine & 
Surgery
USA
ANNE E. BUGLIONE, DVM
Postdoctoral Associate
Department of Neurobiology and 
Behavior
USA
KARAH BURNS DEMARLE, DVM
Staff Internist, Small Animal Internal 
Medicine
Northstar VETS
Robbinsville, New Jersey
USA

lxiJENNA H. BURTON, DVM, MS
Diplomate ACVIM (Oncology)
Associate Professor Clinical Oncology
Department of Surgical and Radiological 
Sciences
USA
JULIE K. BYRON, DVM, MS
Diplomate ACVIM (Small Animal 
Medicine)
Professor—Clinical
Sciences
USA
LAURA CAGLE, DVM
Diplomate ACVECC 
PhD Candidate – Integrative Pathobiology  
USA
KAREN L. CAMPBELL, DVM, MS
Medicine)
Professor Emerita
University of Illinois;
Clinical Professor
Department of Veterinary Sciences
University of Missouri
Veterinary Health Center-Wentzville
Wentzville, Missouri
USA
USA
RENEE T. CARTER, DVM
Associate Professor, Ophthalmology
Sciences
Louisiana State University
Baton Rouge, Louisiana
USAAUDE M.H. CASTEL, DV, MSc
Assistant Professor, Neurology and 
University of Montreal
Canada
MEGAN N. CAUDILL, DVM, MS
and Population Medicine
JULIE T. CECERE, DVM, MS, DACT
Clinical Associate Professor, Theriogenology
Sciences
Virginia-Maryland College of Veterinary 
Medicine
Blacksburg, Virginia
USA
SHARON A. CENTER, DVM
Medicine)
Professor
Cornell University Hospital for Animals
USA
SERGE CHALHOUB, DVM
Medicine)
Senior Instructor, Small Animal Internal 
Medicine
Canada
GEORGINA CHILD, BVSc
Consultant
Small Animal Specialist Hospital
North Ryde;
School of Veterinary Science
University of Sydney
Sydney, NSW
AustraliaBRUCE W. CHRISTENSEN, DVM, MS
Kokopelli Assisted Reproductive Services
Franklin Ranch Pet Hospital
Elk Grove, California
USA
E’LISE CHRISTENSEN BELL
Diplomate ACVB
Owner
Behavior Vets
New Y ork and Colorado
USA
JOHN A. CHRISTIAN, DVM, PhD
Associate Professor of Clinical Pathology
Department of Comparative Pathobiology
USA
RUTHANNE CHUN, DVM
Department of Medical Sciences
University of Wisconsin School of 
Veterinary Medicine
USA
DAVID B. CHURCH, BVSc, PhD, MACVSc, 
FHEA, MRCVS
Professor of Small Animal Studies and 
Deputy Principal
JOHN J. CIRIBASSI, DVM
Chicagoland Veterinary Behavior 
Consultants
Schererville, Indiana
USA
CÉCILE CLERCX, DVM, PhD
Professor
Department of Companion Animal 
Clinical Sciences
University of Liège
Belgium
ANDREANNE CLEROUX
Medicine)
Lecturer in Internal Medicine & 
Interventional Radiology
Department of Clinical Sciences & 
Philadelphia, Pennsylvania
USA

lxii
CRAIG A. CLIFFORD, DVM, MS
Medical Oncologist
Director of Clinical Trials
Hope Veterinary Specialists
USA
JOAN R. COATES, BS, DVM, MS
Professor of Veterinary Neurology & 
Surgery
Columbia, Missouri
USA
SUSAN M. COCHRANE, BSc, MSc, DVM, 
DVSc
Veterinary Emergency Clinic and Referral 
Centre
Toronto, Ontario
Canada
STEVEN M. COGAR, DVM
Carolina Veterinary Specialists
Winston-Salem, North Carolina
USA
WILLIAM M. COLE, DVM
Metropolitan Animal Specialty Hospital
Los Angeles, California
USA
AMANDA E. COLEMAN, DVM, DACVIM 
Associate Professor of Cardiology
University of Georgia College of 
USA
HEATHER E. CONNALL Y , DVM, MS
Veterinary Specialty Center on Tucson 
(retired) 
Associate Veterinarian 
Tucson, Arizona
USA
FRANCISCO O. CONRADO, DVM, MSc
Department of Biomedical Sciences
North Grafton, Massachusetts
USAAUDREY K. COOK, BVM&S, MSc VetEd, 
MRCVS
Medicine)
Diplomate ABVP (Feline Practice)
Professor, Small Animal Internal Medicine
Sciences
College of Veterinary Medicine and 
Biomedical Sciences
Texas A&M University
College Station, Texas
USA
LESLIE LARSON COOPER, DVM
Animal Behavior Counseling and Therapy
USA
EDWARD S. COOPER, VMD, MS
Sciences
Ohio State University
USA
RHIAN COPE, BVSc, BSc(Hon1), PhD, 
FACTRA
Principal Toxicologist
Australian Pesticides and Veterinary 
Medicines Authority
Symonston
Australia
JOHN M. CRANDELL, DVM
Medicine)
Veterinary Internist
MedVet Akron
Akron, Ohio
USA
SIGNE E. CREMER, DVM, PhD
Associate Professor, Clinical Pathology
Sciences
Faculty of Health and Medical Sciences
University of Copenhagen
Frederiksberg
DenmarkSUZANNE M. CUNNINGHAM, DVM
USA
ELIZABETH A. CURRY -GALVIN, DVM
Barrington Hills, Illinois
USA
TERRY MARIE CURTIS, DVM, MS
Veterinary Behaviorist
St. Augustine, Florida
USA
SARAH L. CZERWINSKI, BSc, DVM
USA
RONALDO CASIMIRO DA COSTA, DMV, 
MSc, PhD
Professor and Service Head, Neurology 
and Neurosurgery
Sciences
USA
AUTUMN P . DAVIDSON, DVM, MS
Medicine)
VMTH
University of California
USA
THOMAS K. DAY , DVM, MS
Diplomate ACVAA
Emergency and Critical Care Specialist
Anesthesiology and Pain Management 
Specialist
VCA Veterinary Emergency Service and 
Specialty Center
Middleton, Wisconsin
USA

lxiiiALEXANDER DE LAHUNTA, DVM, PhD
Retired Professor of Veterinary Anatomy 
at Cornell University
USA
HELIO S. AUTRAN DE MORAIS, DVM, PhD
Diplomate ACVIM (Internal Medicine and 
Cardiology)
Director
Lois Bates Acheson Veterinary Teaching 
Hospital
Oregon State University
Corvallis, Oregon
USA
JONATHAN D. DEAR, DVM, MAS
Medicine)
Assistant Professor of Clinical Internal 
Medicine
Department of Medicine and 
USA
TERESA C. DEFRANCESCO, DVM
Diplomate ACVIM (Cardiology), ACVECC
USA
VICTORIA A. DEMELLO, DVM
Nashville Veterinary Specialists
Nashville, Tennessee
USA
SAGI DENENBERG, DVM, MRCVS
Veterinary Psychiatrist
Diplomate ECAWBM
RCVS Recognized Specialist in 
Veterinary Behavioural Medicine
North Toronto Veterinary Behaviour 
Specialty Clinic
Thornhill, Ontario
Canada
THERESA L. DEPORTER, BSc, DVM, 
MRCVS
Diplomate DECAWBM
Behavioral Medicine Department
Oakland Veterinary Referral Services
Bloomfield Hills, Michigan
USANICK DERVISIS, DVM, PhD
DACVIM (Oncology)
Medical Oncology
Sciences;
Faculty of Health Sciences
VA-MD College of Veterinary Medicine
DSACS, Phase II
USA
IAN DESTEFANO, DVM
Resident, Emergency & Critical Care
Foster Hospital for Small Animals
USA
SHARON M. DIAL, DVM, PhD
Diplomate ACVP (Clinical and Anatomic 
Pathology)
Research Scientist
University of Arizona
USA
STEPHEN P . DIBARTOLA, DVM
Medicine)
Professor Emeritus of Internal Medicine
Sciences
USA
DAVID C. DORMAN, DVM, PhD
Professor of Toxicology
Department of Molecular Biomedical 
Sciences
USA
ELIZABETH R. DRAKE, DVM
Sciences
USAEDWARD J. DUBOVI, PhD
Professor of Virology
Animal Health Diagnostic Center
USA
DAVID D. DUCLOS, DVM
Clinical Dermatologist—Animal Skin & 
Allergy Clinic
Lynnwood, Washington
USA
CEDRIC P . DUFAYET, DVM
Advanced Urinary Disease and 
Extracorporeal Therapies Service
University of California Veterinary 
Medicine Center
San Diego, California
USA
STÉPHANIE DUGAS, DVM, MSc
Medical Neurologist
BluePearl Specialty & Emergency Hospital
Irvine, California
USA
ERIC K. DUNAYER, MS, VMD
Senior Toxicologist
ASPCA Animal Poison Control Center
USA
CAROLINA DUQUE, DVM, MSc, DVSc
Mississauga Oakville Emergency Hospital 
and Referral Group
Oakville, Ontario
Canada
DAVID DYCUS, DVM, MS, CCRP
Chief of Orthopedics
Nexus Veterinary Bone & Joint Center
Medical Director
Nexus Veterinary Specialists
Baltimore, Maryland
USA
HEATHER D. EDGINTON, DVM
Animal Medical Center of Seattle
Shoreline, Washington
USA

lxiv
MELISSA N.C. EISENSCHENK, DVM, MS
Owner, Veterinary Dermatologist
Pet Dermatology Clinic
Maple Grove, Minnesota
USA
MARC ELIE, DVM
Diplomate ACVIM (Internal Medicine)
Staff Internist
BluePearl Veterinary Partners
Southfield, Michigan
USA
ROBYN ELLERBROCK, DVM, PhD
Department of Large Animal Medicine
USA
NAHVID M. ETEDALI, DVM
Medicine)
Head of Hemodialysis and Extracorporeal 
Therapies
New Y ork, New Y ork
USA
Professor
USA
JUSTIN FARRIS, DVM
Clinical Pathology Resident
USA
RICHARD A. FAYRER-HOSKEN, BVSc, PhD
Diplomate ECAR
Institute for Conservation Research
San Diego Zoo Global
Escondido, California
USALEAH FERGUSON, DVM, MS
VCA Great Lakes Veterinary Specialists
Warrensville Heights, Ohio
USA
LLUÍS FERRER, BVSc, PhD
Diplomate ECVD
Professor
Department of Animal Medicine and Surgery
Veterinary School
Universitat Autònoma de Barcelona,
Bellaterra, Barcelona
Spain
MARIA SOLEDAD FERRER, DVM, MS
Diplomate DACT (Theriogenology)
USA
TESSA FIAMENGO, DVM, MS
Slade Veterinary Hospital
Framingham, Massachusetts
USA
ANDREA M. FINNEN, DVM, DES, MSc
Mississauga Oakville Veterinary 
Emergency Hospital
Neurology Service
Canada
ANDREA FISCHER, DVM, Dr.med.vet.,  
Dr. habil.
Professor
Centre for Clinical Veterinary Medicine
LMU University of Munich
Munich
Germany
GERRARD FLANNIGAN, DVM, MSc
Kernersville, North Carolina
USA
LINDA M. FLEEMAN, BVSc, PhD, MANZCVS
Animal Diabetes Australia
Melbourne, Victoria
Australia
CHARLOTTE FLINT, DVM, DABT
Senior Consulting Veterinarian, Clinical 
USAJ.D. FOSTER, VMD
Medicine)
USA
DANIEL S. FOY , MS, DVM
Medicine)
Midwestern University
Glendale, Arizona
USA
LINDA A. FRANK, MS, DVM
Professor
Sciences
USA
JONI L. FRESHMAN, DVM MS CVA
Owner
Canine Consultations
Peyton, Colorado
USA
CANNY FUNG, DVM
Surgery Intern
Southwest Veterinary Surgical Service 
Phoenix Arizona 
USA
EVA FURROW, VMD, PhD
Medicine)
Sciences
USA
LUIS GAITERO, DVM
Associate Professor and Head Neurology 
and Neurosurgery Service
HSC Chief Medical Officer
Canada

lxvJOAO FELIPE DE BRITO GALVAO, MV, MS
Medicine)
Internal Medicine Specialist
VCA Arboretum View Animal Hospital
Downers Grove, Illinois;
USA
BRIDGET C. GARNER, DVM, PhD
USA
LAURENT GAROSI, DVM, FRCVS
RCVS and EBVS®
European Specialist in Veterinary 
Neurology
Clinical Director Vet Oracle Teleneurology 
Bedford
LAURA D. GARRETT, DVM
Medicine
University of Illinois
USA
CATHY J. GARTLEY , DVM, DVSc
Department of Population Medicine
Canada
ANNA R.M. GELZER, Dr.med.vet., PhD
Diplomate ECVIM-CA-Cardiology
Professor of Cardiology
Department of Clinical Sciences & 
Advanced Medicine
School of Veterinary Medicine
USAANNE J. GEMENSKY METZLER, DVM, MS
Sciences
USA
KATHERINE GERKEN, DVM, MS
Assistant Clinical Professor
Small Animal Emergency and Critical 
Care
Bailey Small Animal Teaching Hospital
Auburn University
Auburn, Alabama
USA
VIRGINIA L. GILL, DVM
Diplomate DACVIM (Oncology)
Maine Veterinary Medical Center
Scarborough, Maine
USA
MARGI A. GILMOUR, DVM
Professor
Sciences
Oklahoma State University
Stillwater, Oklahoma
USA
ERIC N. GLASS, MS, DVM
Section Head, Neurology and 
Red Bank Veterinary Hospital
Tinton Falls, New Jersey;
Chief of Neurology and Neurosurgery
Compassion First Pet Hospital
USA
USARITA GONC ̧ALVES, DVM, MVM, FHEA, 
MRCVS
European and RCVS Recognized 
Specialist in Veterinary Neurology
Senior Lecturer in Veterinary Neurology
Small Animal Clinical Science
University of Liverpool
Neston, Cheshire
SARA E. GONZALEZ, DVM, MS
Clinical Assistant Professor of Community 
Practice
USA
JENNIFER GOOD, DVM
Diplomate ACVECC (Emergency and 
Critical Care)
Department of Emergency and Critical 
Care
USA
SHARON FOOSHEE GRACE, M Agric, MS, 
DVM
Diplomate ABVP (Canine/Feline)
Mississippi State, Mississippi
USA
W. DUNBAR GRAM, DVM, MRCVS
Clinical Associate Professor and 
Dermatology Service Chief
Small Animal Clinical Sciences, University 
of Florida
USA
JENNIFER L. GRANICK, DVM, PhD
Medicine)
Sciences
USA

lxvi
GREGORY F . GRAUER, DVM, MS
Medicine)
Professor Emeritus
Kansas State University
Manhattan, Kansas
USA
SARAH L. GRAY , DVM
Horizon Veterinary Specialist
Ventura, California
USA
KURT A. GRIMM, DVM, MS, PhD
Diplomate ACVCP
Owner
Veterinary Specialist Services, PC
Conifer, Colorado
USA
AMY M. GROOTERS, DVM
Medicine)
Professor, Companion Animal Medicine
Veterinary Clinical Sciences
USA
MARGARET E. GRUEN, DVM, PhD
Assistant Professor, Behavioral Medicine
USA
SOPHIE A. GRUNDY , BVSc (Hons), 
MANZCVS (Small Animal Internal Medicine)
Medicine)
Internal Medicine Consultant
IDEXX Laboratories, Inc.
Westbrook, Maine
USA
REBEKAH G. GUNN-CHRISTIE, DVM
Veterinary Clinical Pathologist
Antech Diagnostics
Cary, North Carolina
USATALIA GUTTIN, VMD
Medicine)
Small Animal Medicine and Surgery 
Department
St. George’s University
True Blue Campus
St. George, Grenada
West Indies
SHARON GWALTNEY -BRANT, DVM, PhD
Veterinary Information Network
Mahomet, Illinois
USA
TIMOTHY B. HACKETT, DVM, MS
Professor
Colorado State University
Fort Collins, Colorado
USA
DEBORAH J. HADLOCK, VMD
Diplomate ABVP (Canine and Feline)
Certified Veterinary Acupuncturist—CVA 
(IVAS)
Certified Veterinary Spinal Manipulative 
Therapist—CVSMT (HOWC)
Owner
Hadlock Integrative Veterinary Consulting
Salt Lake City, Utah
USA
JENS HÄGGSTRÖM, DVM, PhD
Diplomate ECVIM-CA (Cardiology)
Professor
Faculty of Veterinary Medicine and 
Animal Science
Swedish University of Agricultural 
Sciences
Uppsala
Sweden
FRASER A. HALE, DVM, FAVD
Diplomate AVC
Hale Veterinary Clinic
CanadaEDWARD J. HALL, MA, VetMB, PhD, FRCVS
Emeritus Professor of Small Animal 
Internal Medicine
Langford Vets
Bristol Veterinary School
University of Bristol
Langford
STEVEN R. HANSEN, DVM, MS, MBA
Diplomate ACAW
President and CEO
Arizona Humane Society
Phoenix, Arizona
USA
TISHA A.M. HARPER, DVM, MS, CCRP
Diplomate ACVSMR
Clinical Associate Professor
Medicine
University of Illinois College of Veterinary 
Medicine
USA
JOHN W. HARVEY , DVM, PhD
Department of Physiological Sciences
USA
LORE I. HAUG, DVM, MS
Texas Veterinary Behavior Services
Sugar Land, Texas
USA
ELEANOR C. HAWKINS, DVM
Medicine)
Professor
USA
CRISTINE L. HAYES, DVM
USA

lxviiIAN P . HERRING, DVM, MS
VA-MD Regional College of Veterinary 
Medicine
Virginia Tech
USA
MEGHAN E. HERRON, DVM
Senior Director Behavioral Medicine, 
Education, and Outreach
Gigi’s (Shelter for Dogs)
Canal Winchester, Ohio
USA
MILAN HESS, DVM, MS
Colorado Veterinary Specialty Group
Littleton, Colorado
USA
STEVE HILL, DVM, MS
Medicine)
Small Animal Internal Medicine 
Flagstaff Veterinary Internal Medicine 
Consulting
Flagstaff, Arizona
USA
TRACY HILL, DVM PhD
Medicine)
and Sur gery
USA
LORA S. HITCHCOCK, DVM
Clinical Cardiologist
Ohio Veterinary Cardiology, Ltd
Metropolitan Veterinary Hospital
USA
KATE HOLAN, BS, DVM
Medicine)
Assistant Professor and Head
Sciences
East Lansing, Michigan
USAMASON HOLLAND, VMD
Diplomate ACVR
Staff Radiologist
Port City Veterinary Referral Hospital
Portsmouth, New Hampshire
USA
SUSAN HOLLAND, DVM
Pet Poison Helpline
USA
FIONA HOLLINSHEAD, BVSc (Hons), PhD, 
MANZCVS
Registered Specialist in Small Animal 
Reproduction
Glenbred, Matamata Veterinary Services 
Ltd
Matamata
New Zealand
STEPHEN B. HOOSER, DVM, PhD
Professor of Veterinary Toxicology & Head
Toxicology Section
Department of Comparative Pathobiology 
& ADDL
USA
KATE HOPPER, BVSc, PhD
Associated Professor, Small Animal 
Emergency & Critical Care
Department of Veterinary Surgical & 
Radiological Sciences
USA
DEBRA F . HORWITZ, DVM
Veterinary Behavior Consultations
St. Louis, Missouri
USA
Medicine)
Helpline
Sciences
USATYNE HOVDA, DVM
Anesthesia Intern
USA
JUNE C. HUANG, DVM, PhD
ANTECH Diagnostics
USA
WAYNE HUNTHAUSEN, DVM
Director
Animal Behavior Consultations
Westwood, Kansas
USA
CASSANDRA O. JANSON, DVM
Staff Criticalist
Mount Laurel Animal Hospital
Mount Laurel, New Jersey
USA
NICK D. JEFFERY , BVSc, PhD, MSc, FRCVS
Diplomate ECVS
Professor, Neurology & Neurosurgery
Sciences
USA
ALBERT E. JERGENS, DVM, PhD, AGAF
Medicine)
Professor, Associate Chair for Research 
and Graduate Studies and Donn E. and 
Beth M. Bacon Professor in Small Animal 
Medicine and Surgery
Sciences
Ames, Iowa
USA
JEBA R.J. JESUDOSS CHELLADURAI, 
BVSc, MS, PhD
Ames, Iowa
USA

lxviii
AIME K. JOHNSON, DVM
Diplomate American College of 
Auburn University College of Veterinary 
Medicine
USA
JESSICA JOHNSON, DVM
Senior Dental & Oral Surgery Resident
Elevate Y our Small Animal Dental Team, 
LLC
Main Street Veterinary Hospital & Dental 
Clinic
Dallas, Texas
USA
L YNELLE R. JOHNSON, DVM, MS, PhD
Medicine)
Professor
USA
SPENCER A. JOHNSTON, VMD
James and Marjorie Waggoner Professor
Head
USA
RICHARD J. JOSEPH, DVM
Founder, CEO
AnimalMR.com
VetsOnCall.org
Katonah, New Y ork
USA
RONNIE KAUFMANN, BSc, DVM
Diplomate ECVD (Dermatology)
Head of Dermatology Service
The Veterinary Teaching Hospital
The Hebrew University of Jerusalem
Israel
BRUCE W. KEENE, DVM, MSc
Jane Lewis Seaks Distinguished 
Professor of Companion Animal Medicine
USALISA S. KELL Y , DVM, PhD
USA
DANIEL E. KEYLER, BS, PharmD, FAACT
Senior Clinical Toxicologist
SafetyCall International
Adjunct Professor
Experimental & Clinical Pharmacology
Minneapolis, Minnesota
USA
YUNJEONG KIM, DVM, PhD
Diplomate ACVM (Immunology)
Department of Diagnostic Medicine and 
Pathobiology
USA
SHAWNA L. KLAHN, DVM
Sciences
Medicine
USA
MARY P . KLINCK, DVM, PhD
Veterinary Behavioural Medicine 
Sainte-Anne-de-Bellevue, Quebec
Canada
MARGUERITE F . KNIPE, DVM
Health Sciences Associate Clinical 
Professor, Neurology/Neurosurgery
Sciences
UC Davis School of Veterinary Medicine
USA
JOYCE S. KNOLL, VMD, PhD
Associate Professor and Interim Chair
USAAMIE KOENIG, DVM
Medicine)
USA
CASEY J. KOHEN, DVM
MarQueen Veterinary Emergency and 
Specialty
Roseville, California
USA
BARBARA KOHN, Prof. Dr. med. vet
Clinic for Small Animals
Freie Universität Berlin
Germany
MARC S. KRAUS, DVM
Medicine)
USA
NATALI KREKELER, Dr. med. vet., PhD
Senior Lecturer in Veterinary 
Melbourne Veterinary School
The University of Melbourne
Werribee, Victoria
Australia
ERIKA L. KRICK, VMD
Medical Oncologist and Oncology 
Department Head
USA
PAULA M. KRIMER, DVM, DVSc
Professor & Outreach Services Chief
Athens Veterinary Diagnostic Laboratory 
and Department of Pathology
USA

lxixANNEMARIE T. KRISTENSEN, DVM, PhD
Diplomate ECVIM-CA & Oncology
Professor, Companion Animal Clinical 
Oncology
Denmark
JOHN M. KRUGER, DVM, PhD
Diplomate ACVIM- SAIM
Professor and Carrigan Chair in Feline 
Health
Sciences
USA
STEPHANIE KUBE, DVM, CCRT, CVPP
Veterinary Neurology and Pain 
Management Center of New England
Walpole, Massachusetts
USA
KAREN A. KUHL, DVM
Midwest Veterinary Dermatology Center
Veterinary Specialty Center
Buffalo Grove, Illinois
USA
LEIGH A. LAMONT, DVM, MS
Associate Dean of Academic and Student 
Affairs
Atlantic Veterinary College
University of Prince Edward Island
Charlottetown, Prince Edward Island
Canada
Head
Canada
SELENA LANE, DVM
Clinical Assistant Professor of Small 
Animal Emergency and Critical Care
Small Animal Medicine and Surgery
USACATHY E. LANGSTON, DVM
Medicine)
Professor - Clinical
USA
PATTY A. LATHAN, VMD, MS
Medicine)
USA
KENNETH S. LATIMER, DVM, PhD
Lanexa Veterinary & Consulting Services, 
LLC
Toano, Virginia
USA
ROBIN LAZARO, RVT, VTS(ECC)
ICU Supervisor
North Carolina State Veterinary Hospital
USA
AMY LEARN, VMD
Resident in Clinical Behavior Medicine
Animal Behavior Wellness Center
Richmond, Virginia
USA
MYLÈNE-KIM LECLERC, DMV
Head of the Neurology Service
Centre Veterinaire Rive Sud
Brossard, Quebec
Canada
RICHARD A. LECOUTEUR, BVSc, PhD
Department of Surgical & Radiological 
Sciences
USAMICHAEL S. LEIB, DVM, MS
Medicine)
Emeritus Professor of Internal Medicine
Sciences
Medicine
USA
MATTHEW S. LEMMONS, DVM
Dentistry and Oral Surgery
MedVet
Carmel, Indiana
USA
JOSE A. LEN, DVM, MS, PhD
Assistant Professor, Theriogenology
USA
SOPHIE LE PODER, DVM, MS, PhD
Professor in Virology
Unity of Bacteriology, Immunology and 
Virology
Ecole Nationale Vétérinaire d’ Alfort
Maisons-Alfort
France
JOHN R. LEWIS, VMD, FAVD
Veterinary Dentistry Specialists
Silo Academy Education Center
Chadds Ford, Pennsylvania
USA
ELLEN M. LINDELL, VMD
Central Hospital for Veterinary Medicine
North Haven, Connecticut
USA
MERYL P . LITTMAN, VMD
Medicine)
Professor Emerita of Medicine
USA

lxx
INGRID LJUNGVALL, DVM, PhD
Sciences
Uppsala
Sweden
Flower Mound, Texas
USA
JOHN P . LOFTUS, PhD, DVM
Medicine)
USA
DAWN E. LOGAS, DVM
Owner/Staff Dermatologist
Veterinary Dermatology Center
Maitland, Florida
USA
JAYME S. LOOPER, DVM
Diplomate ACVR (Radiation Oncology)
Sciences
USA
CHERYL LOPATE, MS, DVM
Veterinarian and Owner
Reproductive Revolutions and Wilsonville 
Veterinary Clinic
Wilsonville, Oregon
USA
BIANCA N. LOURENC ̧O, DVM, MSc, PhD
Medicine)
Department of Small Animal and Surgery
USAVIRGINIA LUIS FUENTES, MA, VetMB, PhD, 
CertVR, DVC, MRCVS
Professor
Department of Veterinary Clinical Science 
and Services
Royal Veterinary College
JODY P . LULICH, DVM, PhD
Professor
Sciences
Director of the Minnesota Urolith Center
USA
AL YCEN P . LUNDBERG, DVM
University of Illinois at Urbana-
Champaign
USA
CANDACE C. L YMAN, DVM
USA
KASEY E. MABRY , DVM
Resident, Small Animal Internal Medicine
USA
CATRIONA M. MACPHAIL, DVM, PhD
ACVS Founding Fellow, Surgical 
Oncology
Professor, Small Animal Surgery
USAORLA MAHONY , MVB
Diplomate ECVIM
Cummings School of Veterinary Medicine 
at Tufts University
USA
SEAN B. MAJOY , DVM, MS
USA
GUILLERMINA MANIGOT, DMV UBA
Diplomate CPMV (Dermatology)
Dermlink Buenos Aires
Buenos Aires
Argentina
KATIA MARIONI-HENRY , DMV, PhD, 
MRCVS
Diplomate ACVIM (Neurology) and ECVN
EBVS® European Veterinary Specialist in 
Small Animal Neurology
RCVS Specialist in Veterinary Neurology;
Neurology/Neurosurgery Service
Hospital for Small Animals
Royal (Dick) School of Veterinary Studies
University of Edinburgh
Roslin, Midlothian
STANLEY L. MARKS, BVSc, PhD
Diplomate ACVIM (Internal Medicine, 
Oncology)
Professor
Department of Medicine & Epidemiology
USA
STEVEN L. MARKS, BVSc, MS, MRCVS
Medicine)
Associate Dean, Director of Veterinary 
Medical Services
NC State University
USA

lxxiSINA MARSILIO, Dr.med.vet., PhD
Medicine)
University of California, Davis School of 
USA
DEBBIE MARTIN, LVT, VTS (Behavior)
Veterinary Technician Specialist 
(Behavior)
TEAM Education in Animal Behavior, LLC
Veterinary Behavior Consultations, LLC
Spicewood, Texas
USA
KATY A. MARTIN, DVM, MPH
USDA Resident in Veterinary Parasitology
Graduate Research Assistant
Ames, Iowa
USA
KENNETH M. MARTIN, DVM
Diplomate ACVB (Veterinary 
Behaviorists)
USA
PAULA MARTÍN VAQUERO, DVM, PhD
FCB Health Europe
FCB Health Madrid
Madrid
Spain
KENNETH V. MASON, BSc, MVSc, FACVSc
Veterinary Dermatologist
Managing Director
Dermcare-Vet Pty Ltd
Springwood, Queensland
Australia
PHILIPP D. MAYHEW, BVM&S, MRCVS
Sciences
USATERRI L. MCCALLA, DVM, MS
Animal HealthQuest Solutions LLC
Bellingham, Washington
USA
MEGAN MCCLOSKY , DVM
Clinical Assistant Professor 
University of Pennsylvania School of 
USA
PATRICK L. MCDONOUGH, MS, PhD
Atkinson Center for a Sustainable Future 
Faculty Fellow
Professor Emeritus of Veterinary 
Microbiology
USA
KATHRYN M. MCGONIGLE, MPH DVM
Clinical Small Animal Internal Medicine 
USA
ANNA K. MCMANAMEY , DVM
Veterinary Hospital
USA
STEPHEN MEHLER, DVM
Chief Medical Officer
Veterinarian Recommended Solutions
Blue Bell, Pennsylvania
USA
KRISTINA MEICHNER, DVM
Diplomate ECVIM-CA (Oncology)
USAKATHRYN M. MEURS, DVM, PhD
Professor
North Carolina State University College of 
USA
L YNDA M.J. MILLER, DVM, PhD
Director of Large Animal Clinical Skills
Associate Professor of Theriogenology
Lincoln Memorial University
Harrogate, Tennessee
USA
MATTHEW W. MILLER, DVM, MS
Staff Cardiologist and Cardiology Section 
Head
VetMed Emergency and Specialty Care
USA
PAUL E. MILLER, DVM
Clinical Professor of Comparative 
USA
MELISSA L. MILLIGAN, VMD
Resident in Internal Medicine
The Animal Medical Center
USA
KELL Y MOFFAT, DVM
VCA Mesa Animal Hospital
Mesa, Arizona
USA
SARAH A. MOORE, DVM
Professor
USA
ANDREW R. MOORHEAD, DVM, MS, PhD
Department of Infectious Diseases
USA

lxxii
DANIEL O. MORRIS, DVM, MPH
Professor of Dermatology & Allergy
USA
BRADLEY L. MOSES, DVM
Staff Clinician
VCA Roberts Animal Hospital and
VCA South Shore Animal Hospital
South Weymouth, Massachusetts
USA
JOCEL YN MOTT, DVM
Medicine)
VCA TLC Pasadena Veterinary Specialty 
and Emergency
South Pasadena, California
USA
CHRISTINE MULLIN, VMD
USA
JENNIFER M. MULZ, DVM
Sarasota, Florida
USA
KAREN R. MUÑANA, DVM, MS
Professor, Neurology
USA
LISA A. MURPHY , VMD
Associate Professor of Toxicology
PADLS New Bolton Center Toxicology 
Kennett Square, Pennsylvania
USAANTHONY J. MUTSAERS, DVM, PhD
Canada
USA
GEORGINA M. NEWBOLD, DVM
Assistant Professor- Ophthalmology
Sciences
USA
REBECCA G. NEWMAN, DVM, MS
Pittsburgh Veterinary Medical Specialist 
and Emergency Center
Pittsburgh, Pennsylvania
USA
DENNIS P . O’BRIEN, DVM, PhD
Surgery
USA
LINDA K. OKONKOWSKI, DVM
Internal Medicine Resident, ACVIM 
Small Animal Clinical Sciences
USANATASHA J. OLBY , Vet MB, PhD, MRCVS
Professor of Neurology/Neurosurgery
Dr. Kady M. Gjessing and Rahna 
M. Davidson Distinguished Chair in 
Gerontology
Member of the Comparative Medicine 
Institute
North Carolina State CVM
USA
GAVIN L. OLSEN, DVM
Medicine)
Greensboro, North Carolina
USA
JENNIFER L. OWEN, DVM, PhD
USA
JOANE M. PARENT, DVM, MVetSc
ACVIM Neurology
Professor
Centre Hospitalier Universitaire 
Vétérinaire
Faculté de Médecine Vétérinaire
Montréal
Canada
VALERIE J. PARKER, DVM
Associate Professor, Clinical
Sciences
USA
THOMAS PARMENTIER, DVM
Canada

lxxiiiR. MICHAEL PEAK, DVM
Diplomate AVCD
The Pet Dentist at Tampa Bay
Largo, Florida
USA
KATHERINE L. PETERSON, DVM
USA
MICHAEL E. PETERSON, DVM, MS
Gem Veterinary Clinic
Emmett, Idaho
USA
JASON PIEPER, DVM, MS
Medicine
Champaign
USA
SARAH B. PIERARD, BVSc, PgCertVS, MVS
Australia
AMY L. PIKE, DVM
Owner, Animal Behavior Wellness Center
Fairfax, Virginia 
USA
KATHRYN A. PITT, DVM, MS
Assistant Professor of Small Animal Soft 
Tissue Surgery
USA
AMANDA L. POLDOSKI, DVM
Associate Manager of Veterinary & 
Regulatory Affairs
USADAVID J. POLZIN, DVM, PhD
Professor and Chief of Small Animal 
Sciences
USA
JILL S. POMRANTZ, DVM
Medicine)
Consultant  
IDEXX Laboratories, Inc. 
USA
ERIC R. POPE, DVM, MS
Professor of Surgery
Ross University School of Veterinary 
Medicine
Basseterre
St Kitts
ROBERT H. POPPENGA, DVM, PhD
Head, Toxicology Section
California Animal Health and Food Safety 
USA
SIMON A. POT, DVM
Diplomate ECVO
Equine Department
Vetsuisse Faculty
University of Zurich
Zurich
Switzerland
SILVIA G. PRYOR, DVM
Ophthalmology Service
BluePearl Emergency and Specialty 
Hospital-Irvine
USA
DAVID A. PUERTO, DVM
Center for Animal Referral and 
Emergency Services
Langhorne, Pennsylvania
USABIRGIT PUSCHNER, DVM, PhD
Dean and Professor
USA
ANDHIKA PUTRA, DVM, MS
Dermatology Specialty Intern
USA
BARBARA QUROLLO, MS, DVM
Associate Research Professor
Department of Clinical Sciences-CVM
USA
MARYANN G. RADLINSKY , DVM, MS
Founding Fellow
Minimally Invasive Surgery, Small Animal
Soft Tissue Surgeon
Salt River Veterinary Specialists
Scottsdale, Arizona
USA
LISA RADOSTA, DVM
Florida Veterinary Behavior Service
West Palm Beach, Florida
USA
ELEANOR RAFFAN, BVM&S, PhD,
CertSAM, MRCVS
University Lecturer in Systems Physiology
Department of Physiology, Development 
and Neuroscience
University of Cambridge
Cambridge 
MERL F . RAISBECK, DVM, MS, PhD
Emeritus Professor
Department Veterinary Sciences
University of Wyoming
Laramie, Wyoming
USA
LAURA RAYHEL, DVM
Department of Medicine
Midwestern University 
USA

lxxiv
JONJO REECE, DVM, ECFVG, BSc
Small Animal Internal Medicine Resident
USA
TABATHA J. REGEHR, DVM
Helpline
USA
MARSHA R. REICH, DVM
Maryland-Virginia Veterinary Behavioral 
Silver Spring, Maryland
USA
JENNIFER M. REINHART, DVM, PhD
Medicine)
Medicine
University of Illinois Urbana-Champaign
USA
ILANA R. REISNER, DVM, PhD
Reisner Veterinary Behavior Services, 
LLC
Wallingford, Pennsylvania
USA
ALEXANDER M. REITER, Dipl.Tzt., Dr.med.vet
Diplomate AVDC, Diplomate EVDC
Professor of Dentistry and Oral Surgery
USA
LISA RESTINE, DVM
Alamo Feline Health Center
San Antonio, Texas
USA
AUSTIN RICHMAN, DVM
USASHARON L. RIPPEL, DVM
Clinical Toxicologist
USA
WESLEY J. ROACH, DVM
Head of Surgery Department
USA
TRACIE D. ROMSLAND, DVM, MS
Staff Clinical Pathologist
USA
KATHRYN A. ROOK, VMD
Assistant Professor of Clinical Dermatology
USA
SHERI ROSS, BSc, DVM, PhD
Coordinator
University of California Veterinary Medical 
Center - San Diego
USA
JAMES K. ROUSH, DVM, MS
Doughman Chair Professor
USA
Diplomate DACVIM (Small Animal Internal 
Medicine)
USARENEE RUCINSKY , DVM
Mid Atlantic Cat Hospital
Mid Atlantic Feline Thyroid Center
Queenstown, Maryland
USA
ELKE RUDLOFF , DVM, CVMA
Clinical Specialist
Emergency and Critical Care
Lakeshore Veterinary Specialists
Glendale, Wisconsin
USA
HÉLÈNE L.M. RUEL, DVM, DES, MSc
Saint-Hyacinthe, Québec
Canada
WILSON K. RUMBEIHA, BVM, PhD, ATS
Professor of One Environmental Health 
Department of Molecular Biosciences
USA
ERIN E. RUNCAN, DVM
Theriogenology and Reproductive 
Medicine
Sciences
USA
CLARE RUSBRIDGE, BVMS, PhD, FRCVS
Professor in Veterinary Neurology
University of Surrey
Faculty of Health & Medical Sciences
Guildford, Surrey

lxxvJOHN E. RUSH, DVM, MS
Professor
USA
KAREN E. RUSSELL, DVM, PhD
Professor and Associate Department 
Head for Clinical Services and Residency 
Programs
Department of Veterinary Pathobiology
College of Veterinary Medicine & 
USA
SHERISSE A. SAKALS, DVM
VCA Vancouver Animal Emergency & 
Vancouver, WA
Canada
CARL D. SAMMARCO, BVSc MRCVS
Head of Cardiology
USA
SHERRY L YNN SANDERSON, BS, DVM, PhD
Medicine)
Department of Veterinary Biosciences 
and Diagnostic Imaging
USA
DOMENICO SANTORO, DVM, MS, DrSc, 
PhD
Diplomate ACVM (Bacteriology/Mycology/
Immunology)
Sciences
USAASHLEY B. SAUNDERS, DVM
Department of Veterinary Small Animal 
USA
BRIAN A. SCANSEN, DVM, MS
Associate Professor and Service Head, 
Cardiology & Cardiac Surgery
USA
MICHAEL SCHAER, DVM
Medicine)
Adjunct Professor, Emergency and 
Critical Care Medicine
USA
THOMAS SCHERMERHORN, VMD
Medicine)
Professor and Jarvis Chair
USA
PHILIP SCHISSLER, DVM
Staff Neurologist/Neurosurgeon
Veterinary Neurology Center
Tustin, California
USA
RENEE D. SCHMID, DVM
USAKARSTEN E. SCHOBER, DVM, MS, PhD
Professor
Head, Cardiology and Interventional 
Medicine
Sciences
USA
GRETCHEN L. SCHOEFFLER, DVM
Chief, Emergency and Critical Care
USA
JOHAN P . SCHOEMAN, BVSc, 
MMedVet(Med)(Pretoria), PhD(Cantab), 
DSAM(RCVS-UK)
RCVS Recognized Specialist in Small 
Animal Medicine;
Professor
Clinical Studies
Chair, Pathobiology Research
Faculty of Veterinary Science
University of Pretoria
Onderstepoort
South Africa
DONALD P . SCHROPE, DVM
Department of Cardiology
Oradell Animal Hospital
Paramus, New Jersey
USA
ERIN M. SCOTT, VMD
Sciences
USA
CHRISTOPHER J. SCUDDER, BVSc, 
MVetMed, PhD, MRCVS
Diplomate ACVIM-SAIM
Head of Internal Medicine
Southfields Veterinary Specialists
Essex

lxxvi
L YNNE M. SEIBERT, DVM, MS, PhD
Veterinary Behavior Consultants LLC
Lawrenceville, Georgia
USA
ASHLEIGH SEIGNEUR, DVM, MVSc
Internal Medicine Department
South Carolina Veterinary Specialists and 
Emergency Care
Columbia, South Carolina
USA
KIM A. SELTING, DVM, MS
Medicine
USA
LINDA G. SHELL, DVM
Veterinary Neurology Education and 
Pilot, Virginia
USA
BARBARA L. SHERMAN, MS, PhD, DVM
Diplomate ACVB (Behavior) & ACAW 
(Animal Welfare)
Clinical Professor Emerita
USA
TRACI A. SHREYER, MA
Applied Animal Behaviorist
USA
DEBORAH C. SILVERSTEIN, DVM
Professor of Critical Care
USALESLIE SINN, DVM
Specialist in Behavior
Behavior Solutions
Hamilton, Virginia
USA
KIM SLENSKY , DVM
Assistant Professor of Clinical Emergency 
and Critical Care
USA
FRANCIS W.K. SMITH, JR., DVM
Diplomate, ACVIM (Small Animal Internal 
Medicine and Cardiology)
VetMed Consultants, Inc.
USA
MARK M. SMITH, VMD
Founding Fellow, ACVS Oral & 
Maxillofacial Surgery
Founding Fellow, AVDC Oral & 
Center for Veterinary Dentistry and Oral 
Surgery
Gaithersburg, Maryland
USA
PATRICIA J. SMITH, MS, DVM, PhD
PJSmith Animal Eye Consulting
Adjunct Ophthalmologist Animal Eye Care
Milpitas, California
USA
CHRISTOPHER J. SNYDER, DVM
Dentistry and Oral Surgery, Department 
of Surgical Sciences
USA
PAUL W. SNYDER, DVM, PhD
Diplomate ACVP (Anatomical Pathology)
Fellow, International Academy Toxicologic 
Pathologists
Senior Pathologist
Experimental Pathology Laboratories, Inc.
Bonita Springs, Florida
USALAIA SOLANO-GALLEGO, DVM, PhD
Professora Agregada (Associate Professor)
Departament de Medicina i Cirurgia Animals
Facultat de Veterinària
Universitat Autònoma de Barcelona
Barcelona
Spain
MITCHELL D. SONG, DVM
Animal Dermatology, PC
Phoenix, Arizona;
Adjunct Assistant Clinical Professor
USA
JASON W. SOUKUP , DVM
Dentistry and Oromaxillofacial Surgery
USA
SAMANTHA B. SOUTHER, DVM
Associate Veterinarian, Theriogenology
Mohnacky Animal Hospitals
Carlsbad, California
USA
CLARISSA P . SOUZA, DVM, MS, PhD
Assistant Professor of Dermatology and 
Otology
Medicine
Urbana-Champaign, Illinois
USA
JÖRG M. STEINER, MedVet, DrVetMed, 
PhD, AGAF
University Distinguished Professor
Dr. Mark Morris Chair in Small Animal 
Gastroenterology and Nutrition
Director, Gastrointestinal Laboratory
Sciences
USA

lxxviiKEVIN S. STEPANIUK, DVM, FAVD
Veterinary Dentistry Education and 
Consulting Services
Ridgefield, Washington
USA
JOSHUA A. STERN, DVM, PhD
USA
VICTOR J. STORA, DVM
Postdoctoral Fellow Transgenesis & Large 
Animal Model Creation
Vite Lab, Referral Center for Animal 
Models
USA
JAN S. SUCHODOLSKI, MedVet, DrVetMed, 
PhD, AGAF
Small Animal Medicine
Associate Director for Research
Head of Microbiome Sciences
Gastrointestinal Laboratory
Sciences
USA
AL YSSA M. SULLIVANT, DVM, MS
Medicine)
Mississippi State, Mississipi
USA
ANNIKA SUNDBY , DVM
Rotating Intern
USAWAILANI SUNG, MS, PhD, DVM
Behavior Service
The San Francisco Society for the 
Prevention of Cruelty to Animals (SPCA)
USA
STEVEN E. SUTER, VMD, MS, PhD
Professor
USA
JANE E. SYKES, BVSc(Hons), PhD
Medicine)
Medicine
USA
JOSEPH TABOADA, DVM
Professor and Associate Dean
Sciences
USA
LAUREN TALARICO, BS, DVM
Section Head Neurology/Neurosurgery
VCA Southpaws Veterinary Specialty & 
Emergency Center
Fairfax, Virginia
USA
PATRICIA A. TALCOTT, MS, DVM, PhD
Professor
Department of Integrative Physiology and 
Neuroscience
Washington State University
Pullman, Washington
USA
KENDALL TANEY , DVM
Surgery
USAJAIME L. TARIGO, DVM, PhD
USA
DOMINIC A. TAUER, DVM
Consulting Veterinarian in Clinical 
Pet Poison Helpline and
SafetyCall International, PLLC
USA
SUSAN M. TAYLOR, DVM
Sciences
Western College of Veterinary Medicine
University of Saskatchewan
Saskatoon, Saskatchewan
Canada
MICHELLE C. TENSLEY , DVM, MS
Associate Neurologist
The Animal Neurology and Imaging Center
USA
VINCENT J. THAWLEY , VMD
Emergency and Critical Care Medicine
USA
JUSTIN D. THOMASON, DVM
Diplomate ACVIM (Cardiology; SAIM)
USA
CRAIG A. THOMPSON, DVM
Diplomate ACVP
Clinical Associate Professor - Clinical 
Pathology
Purdue University- College of Veterinary 
Medicine
USA

lxxviii
JERRY A. THORNHILL, DVM
Director, Nephrology & Dialysis
Division of Internal Medicine
USA
MARY ANNA THRALL, BA, DVM, MS
Professor
Medicine
Basseterre, St. Kitts
LARRY P . TILLEY , DVM
Medicine)
President
USA
ANDREA TIPOLD, DVM
Diplomate ECVN (Veterinary Neurology)
University of Veterinary Medicine 
Hannover
Hannover
Germany
SHEILA M.F . TORRES, DVM, MS, PhD
Diplomate ACVD (Dermatology)
Professor
Sciences
USA
SANDRA P . TOU, DVM
Diplomate ACVIM (Cardiology and 
Clinical Assistant Professor of Cardiology
USA
WILLIAM J. TRANQUILLI, Bs in Ed, Ms, 
DVM
Departments of Clinical Science, 
Biological Sciences, and Pathobiology
University of Illinois-Urbana
Illinois
USAVALARIE V. TYNES, DVM
Diplomate ACVB (Veterinary Behavior)
Diplomate ACAW (Animal Welfare)
Veterinary Services Specialist
Ceva Animal Health
Lenexa, Kansas
USA
YU UEDA, DVM, PhD
Small Animal Emergency and Critical Care
USA
STEFAN UNTERER, Dr.med.vet., Dr. habil.
Head of Gastroenterology Service
Clinic of Small Animal Internal Medicine
Ludwig-Maximilians-University
Munich
Germany
SHELL Y VADEN, DVM, PhD
Professor, Small Animal Nephrology and 
Urology
USA
SUZY Y .M. VALENTIN, DVM, MS
Diplomate ECVIM-CA (Internal Medicine)
Internal Medicine Service
Centre Hospitalier Vétérinaire Pommery
Reims 
France
MEGHAN VAUGHT, DVM
Staff Criticalist;
ECC Medical Director
Maine Veterinary Medicine Center
USA
GUILHERME G. VEROCAI, DVM, MSc, PhD
Director Parasitology Diagnostic 
USAMARIA VIANNA, DVM
Diplomate DACVS
USA
AL YSHA VINCENT, DVM
Internal Medicine Resident (Small Animal 
Sciences
USA
KAREN A. VON DOLLEN, DVM, MS
Hagyard Equine Medical Institute
Lexington, Kentucky
USA
DIRSKO J.F . VON PFEIL, Dr.med.vet, DVM
Sirius Veterinary Orthopedic Center
Omaha, Nebraska;
Small Animal Surgery Locum, PLLC
USA
LORI S. WADDELL, DVM
Professor, Clinical Critical Care
Department of Clinical Studies and 
Advancement of Medicine
USA
LIORA WALDMAN, BVM&S, MRCVS
CertSAD
Dermatology and Allergy Clinic
Haifa
Israel
JULIE M. WALKER, DVM
USA

lxxixREBECCA A.L. WALTON, DVM
Ames, Iowa
USA
STUART A. WALTON, BVSc, BScAgr
Medicine)
Sciences
USA
ANDREA WANG MUNK, MA, DVM
Medicine)
Small Animal Internal Medicine Consultant
USA
KIRSTEN E. WARATUKE, DVM
Toxicologist
USA
BRETT A. WASIK, DVM
Medicine)
Antech Diagnostics - Internal Medicine/
Endocrinology Consultant
Veterinary Information Network - Internal 
Medicine/Endocrinology Consultant
UC Davis Endocrinology Post-doctorate
Allen, Texas
USA
NICOLE M. WEINSTEIN, DVM
USA
GLADE WEISER, DVM
Diplomate ACVP Emeritus
Clinical Pathologist
Loveland, Colorado
USASARA A. WENNOGLE, DVM, PhD
USA
MICHAEL D. WILLARD, DVM, MS
Senior Professor
Sciences
USA
LAUREL E. WILLIAMS, DVM
Oncologist  , Medical Director
Veterinary Specialty Center of Seattle
Lynwood, Washington
USA
HEATHER M. WILSON-ROBLES, DVM
Professor
Department of Veterinary Small
Animal Clinical Sciences
USA
TINA WISMER, DVM, MS
USA
EWAN D.S. WOLFF , PhD, DVM
Small Animal Internist
BluePearl - Affiliated Veterinary 
Specialists
USA
MICHAEL W. WOOD, DVM, PhD
Medicine)
USAR. DARREN WOOD, DVM, DVSc
Canada
J. PAUL WOODS, DVM, MS
Oncology)
Professor of Internal Medicine and 
Oncology
Ontario Veterinary College;
Co-Director
Institute for Comparative Cancer 
Investigation
Canada
CORRY K. YEUROUKIS, DVM, MS
Diplomate ACVP (Clinical)
Annapolis, Maryland
USA
HANY YOUSSEF , BVSc, MS, DVM
Watseka Animal Hospital
Watseka, Illinois;
Iroquois County Animal Control Director
Watseka, Illinois
USA
DANIELLE ZWUESTE, DVM
Vancouver Animal Emergency and 
Referral Centre
Vancouver
British Columbia
Canada

lxxx
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Canine and Feline, Seventh Edition  1
A
 5-Fluorouracil (5-FU) Toxicosis
  BASICS
OVERVIEW
• Antimetabolite, antineoplastic agent; it is 
metabolized to thymidine, which blocks the 
methylation reaction of deoxyuridylic and 
thymidylic acids, resulting in thymine 
deficiency; thymine is critical for DNA and 
to a lesser extent RNA replication; the result 
is cell death due to interruption of normal 
DNA and RNA synthesis; this mechanism 
targets rapidly growing cells like bone marrow 
and intestinal crypts; 5-FU has various active 
metabolites resulting in delayed clearance 
from bone marrow and γ-aminobutyric acid 
(GABA) depletion in the brain.
• Labeled for human use only.
• Topical preparation for actinic and solar 
keratoses: Efudex® (5% cream, 2% and 5% 
solution), Carac® (0.5% cream), Fluoroplex® 
(1% cream), Tolak® (4% cream).
• IV preparation used for a variety of neoplastic 
conditions: Adrucil® (50 mg/m: IV solution).
• Causes acute and severe gastroenteritis and 
seizures; seizures can develop within 30 minutes to 
6 hours post exposure; bone marrow suppression 
occurs 7–21 days after acute presentation.
• Patients may survive acute toxicity to 
succumb to bone marrow suppression later.
• Any suspected exposure in animals warrants 
immediate veterinary evaluation.
SIGNALMENT
• No species or breed predilection.
SIGNS
• Cardiovascular—hypotension, myocardial 
ischemia, arrhythmias.
• Immune—bone marrow suppression of all 
cell lines.
• Gastrointestinal (GI)—nausea, salivation, 
profuse vomiting, hematemesis, diarrhea, 
hematochezia, abdominal pain, stomatitis.
• Nervous—lethargy, ataxia, depression, 
disorientation, tremors, seizures (often 
refractory to treatment), death.
• Ophthalmic—blindness (cats).
• Reproductive—teratogenic, embryotoxic.
• Respiratory—noncardiogenic pulmonary 
edema, dyspnea, cyanosis, tachypnea.
CAUSES & RISK FACTORS
• Access to topical preparations in the home.
• Cats and small dogs may be exposed by 
licking pet owner.
• Pets in geographic locations of high human 
UV exposure due to increased human use.
  DIAGNOSIS
DIFFERENTIAL DIAGNOSIS
• Other toxins—bromethalin, castor bean, 
cycad palms ( Cycas  and Zamia  spp.), disulfoton, iron, metaldehyde, mushrooms ( Amanita , 
Galerina , and Lepiota  spp.), sodium fluoroac-
etate (Compound 1080), strychnine.
• Metabolic—hepatic failure, hepatic 
encephalopathy.
• Nervous—idiopathic epilepsy, meningitis, 
neoplasia.
CBC/BIOCHEMISTRY/URINALYSIS
• CBC—baseline, then continue to monitor 
q3–4 days post exposure for 21 days; monitor 
for echinocytes; leukopenia develops by day 7 
and continues to day 13; thrombocytopenia 
develops by day 7 and can continue for 21 
days; acute anemia due to blood loss can be 
secondary to bone marrow suppression by 
day 9, persisting until day 21.
• Chemistry—baseline; hepatic values may 
increase.
• Electrolytes—baseline; recheck PRN based 
on GI losses.
OTHER LABORATORY TESTS
• Blood gases—metabolic acidosis can occur; 
monitor PRN.
• Packed cell volume (PCV)/total protein 
(TP) q6–24h.
• Blood glucose q2–4h.
IMAGING
N/A
DIAGNOSTIC PROCEDURES
N/A
  TREATMENT
• Emesis—not typically indicated due to 
rapid onset of seizures.
• Single dose activated charcoal with sorbitol 
in asymptomatic patients; seizures may develop 
before opportunity to administer charcoal.
• Gastric lavage can be performed in patients 
with recent exposure; a single dose of 
activated charcoal with a cathartic (AC/C) 
can be administered, recovering patient with 
endotracheal tube in place.
• Balanced crystalloid IVF to maintain 
hydration, aid in elimination, and maintain 
perfusion.
• Monitor blood pressure q4–6h.
  MEDICATIONS
DRUG(S) OF CHOICE
• Anticonvulsant—levetiracetam 60 mg/kg 
IV loading dose, 20 mg/kg IV q8h; propofol 
4–6 mg/kg IV bolus followed by 0.6 mg/kg/
minute CRI; inhalant anesthesia; valium is 
typically ineffective; phenobarbital and 
pentobarbital have unpredictable efficacy, but 
can be attempted, phenobarbital 5–8 mg/kg 
IV slowly to effect.• Antiemetic—maropitant 1 mg/kg IV, SC 
q24h; ondansetron 0.1–0.2 mg/kg IV 
q6–12h; metoclopramide 0.1–0.5 mg/kg IV, 
SC q6–8h.
• GI protection—proton pump inhibitors, 
H2 blockers, sucralfate.
• Analgesia—buprenorphine 0.005–0.03 mg/kg 
IM or IV q6–12h, butorphanol 0.1–0.5 mg/kg 
SC, IV, or IM.
• Antibiotic—broad-spectrum antibiotic 
therapy if total white blood cell count is 
below 2000.
• Bone marrow stimulation—filgrastim 
(Neupogen®) 4–6  μg/kg SQ q24h.
• T ransfusion therapy may be indicated if 
PCV <20%.
• 20% intravenous fat emulsion (IFE) 
unlikely to be effective.
• Antidote—uridine triacetate has not been 
used in veterinary medicine; must be 
instituted prior to development of CNS signs; 
cost prohibitive.
CONTRAINDICATIONS/POSSIBLE 
INTERACTIONS
• Avoid nonsteroidal anti-inflammatory 
drugs (NSAIDs) and CNS depressants.
  FOLLOW-UP
• CBC q3–4 days for 21 days or more.
  MISCELLANEOUS
ABBREVIATIONS
• 5-FU = 5-fluorouracil.
• AC/C = activated charcoal with a cathartic.
• GABA = γ-aminobutyric acid.
• GI = gastrointestinal.
• IFE = intravenous fat emulsion.
• NSAID = nonsteroidal anti-inflammatory 
drug.
• PCV = packed cell volume.
• TP = total protein.
 Suggested Reading
Sayre RS, Barr JW, Bailey EM. Accidental 
and experimentally induced 5-fluorouracil 
toxicity in dogs. J Vet Emerg Crit Care 
2012; 22(3):545–549.
Author  Tabatha J. Regehr
Consulting Editor  Lynn R. Hovda

2 Blackwell’s Five-Minute Veterinary Consult  
AAbortion, Spontaneous (Early Pregnancy Loss)—Cats
  BASICS
DEFINITION
• Abortion: loss of a pregnancy at any time 
prior to the fetus’s ability to survive outside 
the uterus. • Early pregnancy loss: loss of a 
pregnancy and death of conceptus within the 
first half of gestation
PATHOPHYSIOLOGY
• Noninfectious causes—more common. 
• Infectious causes—direct infection of 
embryo, uterus, placenta, or fetuses, or 
indirectly by systemic infection.
SYSTEMS AFFECTED
• Reproductive. • Endocrine. • Other 
systems resulting in debilitating illness.
GENETICS
Higher incidence in purebred or closed 
research catteries with closely related 
individuals; heritability of susceptibility to 
feline infectious peritonitis virus (FIPV) 
suspected to be high.
INCIDENCE/PREVALENCE
Difficult to determine, as pregnancy may not 
be diagnosed early. Loss or resorption of one 
or two conceptus within a litter is not 
uncommon.
GEOGRAPHIC DISTRIBUTION
N/A
Increased incidence in queens >5 years old; 
increased risk in purebred cats with high 
inbreeding.
SIGNS
General Comments
Frequently no clinical symptoms other than 
lack of pregnancy or reduced litter size.
Historical Findings
Failure to deliver kittens at expected due date, 
return to estrus sooner than expected 
(approximately 45 days), discovery of fetal 
tissues or placenta, behavior change, systemic 
illness.
Physical Examination Findings
Signs range from normal to dehydration, 
fever, abdominal straining, and discomfort to 
presence of purulent, mucoid, watery, or 
sanguineous vaginal discharge.
CAUSES
Infectious
• Bacterial—organisms implicated in causing 
abortion via ascending infection through the 
vaginal vault and cervix include E. coli , 
Staphylococcus  spp., Streptococcus  spp., 
Chlamydia  spp., Pasteurella  spp., Klebsiella  spp., 
Pseudomonas  spp., Salmonella  spp., Mycoplasma  
spp., and Ureaplasma  spp. • Protozoal—
Toxoplasma gondii . • Viral— feline leukemia virus (FeLV), feline herpesvirus 1 (FHV-1), 
FIP , feline immunodeficiency virus (FIV), 
feline panleukopenia virus (FPLV).
Noninfectious
• Uterine—cystic endometrial hyperplasia, 
endometritis, pyometra, anatomic 
abnormalities of uterus (e.g., adhesions or 
strictures), uterine trauma. • Ovarian— 
primary hypoluteoidism is rare in cats, but 
secondary hypoluteoidism may result from 
prostaglandin exposure, prolonged stress, and 
uterine inflammation. • Fetal—chromosomal 
abnormalities resulting in abnormal or 
arrested development and embryonic or fetal 
death. • Systemic—malnutrition or nutrit  - 
ional disorders (e.g., taurine deficiency, 
vitamin A deficiency or toxicity), severe 
nonreproductive illness, exposure to 
exogenous estrogens, glucocorticoids, 
chemotherapeutic agents, antifungal agents, 
some antibiotics (trimethoprim–sulfonamides, 
tetracyclines, gentamicin), modified live 
vaccines.
RISK FACTORS
• Cats with high coefficient of inbreeding 
(COI). • Previous pregnancy loss. • Previous 
history of reduced litter size. • Evidence of 
cystic endometrial hyperplasia (CEH) on 
ultrasound. • Concurrent systemic disease or 
recent trauma. • Older queens (over 6 years). 
• Malnourishment. • Unsanitary housing 
conditions. • Raw diets.
  DIAGNOSIS
• Early pregnancy loss—failure to ovulate, 
failure to conceive, chromosomal disorder, or 
disorder of sexual development. • Vaginal 
discharge—pyometra, uterine stump 
pyometra, mucometra, vaginitis, neoplasia, 
cystitis, active labor or impending abortion, 
trauma to urogenital tract. • Mass or tissue 
from vaginal vault—dystocia, neoplasia, 
hemorrhage/blood clot, uterine prolapse.
• Generally normal. • Inflammatory leuko- 
 gram with infection or systemic disease. 
• Anemia of pregnancy; hemoconcentration 
and azotemia may be seen with dehydration 
or hypovolemia.
Infectious Causes
• Cytology and bacterial culture of vaginal 
discharge, fetus, fetal membranes, or uterine 
contents (aerobic and mycoplasma). 
• FeLV—test for antigens in queens using 
ELISA or indirect fluorescent antibody (IFA). 
• FHV-1—IFA or PCR from corneal or 
conjunctival swabs, viral isolation from 
conjunctival, nasal, or pharyngeal swabs. • FIP—submit fetal tissue for histopathology 
and immunohistochemistry. • FIV—ELISA: 
confirm positive results with Western blot. 
• FPLV—viral isolation from fetuses 
submitted for necropsy; document serocon -
version in queen.
Noninfectious Causes
• To rule out anovulatory cycle, confirm 
progesterone >2 ng/mL one week following 
mating. • Hypoluteoidism—serum 
progesterone level <1.0 ng/mL prior to 
abortion indicates luteal failure. • Disorder of 
sexual development—evaluate external 
genitalia, karyotype, and histopathology of 
reproductive tract and gonads.
IMAGING
• Abdominal ultrasound—most specific; 
pregnancy confirmed after 25 days. 
Re-ultrasound every 1–2 weeks for high-risk 
queens. Confirm fetal heart rates and assess 
fetal fluids and placenta in late gestation 
(normal fetal heart rates >200 bpm). 
Visualization of fetal kidney and intestinal 
peristalsis indicates fetal maturity. 
• Abdominal radiographs—after 45 days, can 
evaluate fetal number, relative size, and 
position; also assess fetal death (gas pockets) 
or fetal malformation.
• Submit aborted, stillborn, mummified 
fetuses and fetal membranes (fresh or 
refrigerated on ice) for gross necropsy, 
histopathology, cultures, and viral isolation. 
Submit culture of reproductive tract or entire 
tract if removed (uterus, ovaries, oviducts). 
Submit samples from aborted and stillborn 
fetus for karyotyping. • Pedigree analysis—
evaluate COI. • Evaluate cattery management 
for vaccination protocols, feeding regime, 
sanitation procedures, and quarantine 
procedures. • Nutrition—nutritional analysis 
of diet: of particular importance when queen 
is fed homemade and/or raw diet.
PATHOLOGIC FINDINGS
Variable with etiology.
  TREATMENT
APPROPRIATE HEALTH CARE
None, for noninfectious, stable queens; 
primary hypoluteoidism—managed on 
outpatient basis.
NURSING CARE
Inpatient management if systemically ill, 
debilitated, severely dehydrated, or for 
medical management of ongoing fetal loss or 
pyometra.
ACTIVITY
• Isolation for queens with infectious disease. 
• No activity restrictions for most; restrict 
activity as indicated if due to trauma.

Canine and Feline, Seventh Edition  3
A
DIET
• Feed commercially available diet labeled for 
use in pregnancy. • Correct diets with 
inappropriate taurine or vitamin A concen -
trations. • Avoid feeding raw meats or 
allowing queens to hunt during pregnancy to 
reduce risk for ingestion of pathogenic 
bacteria and T. gondii .
CLIENT EDUCATION
• Infectious diseases—verify vaccination 
status (vaccinate prior to pregnancy) and 
disease surveillance measures; ensure use of 
quarantine facilities for pregnant queens and 
new arrivals. • Breeding management—keep 
detailed records of reproductive performance, 
pedigree analysis, and social behavior of 
queens (including when not receptive to male). 
• Nutrition—advise feeding commercial cat 
food during pregnancy. • Genetic disease—
discuss COI and value of introducing new 
genetics. • Discuss risk of zoonotic disease 
from T. gondii .
SURGICAL CONSIDERATIONS
Ovariohysterectomy (OHE) may be 
considered if queen is systemically ill from 
uterine infection or deceased fetuses. If 
valuable breeding animal, Cesarean section 
can be performed to remove deceased fetuses.
• Depends on etiology. • Amoxicillin–
clavulanic acid 13.75 mg/kg PO q12h—safe for 
pregnancy. • Enrofloxacin 5 mg/kg/day PO—
excellent penetration to uterus; contraindicated 
if live fetuses present. • Prostaglandin F2α 
(PGF2α; dinoprost/Lutalyse®) 80–100  μg/kg 
IM q8–12h—promotes uterine contractions, 
loss of corpus luteum, and cervical opening to 
expulse aborted materials. • Tocolytics—
prevent uterine contractions: terbutaline 
0.03–1.0 mg PO as needed based on tocodyna -
mometry (www.whelpwise.com); 0.03 mg/kg 
PO q8h if tocodynamometry not available. 
• Hypoluteoidism—oral progestogene 
(altrenogest) 0.088 mg/kg PO q24h to 
maintain pregnancy; can monitor queen’s 
progesterone, as altrenogest will not interfere 
with progesterone assay.
CONTRAINDICATIONS
• Terbutaline—cardiac disease, pyometra, 
infectious disease, hypertension. 
• Altrenogest—contaminated uterus with 
systemically ill queen. • Prostaglandin-cats 
with previously diagnosed respiratory disease.
PRECAUTIONS
• Use of tocolytics requires accurate breeding 
dates to know when to stop treatment; most 
successful in combination with tocodyna -
mometry. • Terbutaline can cause hypertension leading to hemorrhage from 
placental sites during parturition or at time of 
Cesarean section. • Altrenogest can cause 
agalactia and failure of parturition, leading to 
death of litter; discontinue use 2 days before 
due date. • Caution with use of altrenogest 
with infectious processes or necrotic fetuses in 
uterus; may keep infection within uterus, 
causing metritis and systemic illness; monitor 
pregnancy often with ultrasound. • PGF2α—
side effects vomiting, hypersalivation, 
defecation, urination, and tachypnea; dose 
dependent and self-limiting.
POSSIBLE INTERACTIONS
• Progesterone administration during 
pregnancy associated with masculinization of 
female fetuses; do not administer in first half 
of pregnancy and use with informed consent 
thereafter. • Tocolytics associated with 
increased risk of dystocia, failure of placental 
separation, lack of milk production, and poor 
maternal behavior for first days postpartum.
ALTERNATIVE DRUG(S)
Dopamine agonists (e.g., cabergoline 5  μg/kg 
PO q24h) can be used to lower progesterone 
and facilitate uterine emptying. Use in 
conjunction with low dose of PGF2α.
  FOLLOW-UP
PATIENT MONITORING
• Serial ultrasound—follow pregnancy loss, 
uterine emptying, or viability of remaining 
fetuses; initially daily; decrease frequency 
when stable, continue until birth (with partial 
loss) or uterus is free of fluid (complete 
abortion). • Monitor health and attitude of 
queen. • If live fetuses are present—delayed 
parturition my occur with progesterone or 
terbutaline treatment; Cesarean section may 
be necessary.
PREVENTION/AVOIDANCE
• Institute infectious disease prevention, 
control, and surveillance. • Replace subfertile 
queens with more reproductively fit individ -
uals. • Avoid exposure to abortifacient, 
teratogenic, or fetotoxic drugs. • Serial 
progesterone assays and fetal ultrasound 
during next pregnancy.
POSSIBLE COMPLICATIONS
• Loss of entire litter. • Metritis, chronic 
endometritis, uterine rupture, sepsis, shock. 
• Uterine pathology. • Masculinization of 
female fetuses with progesterone therapy.
EXPECTED COURSE AND PROGNOSIS
• Poor prognosis for live kittens for current 
litter, even with aggressive monitoring and 
treatment. • May recur in future pregnancies 
depending on cause and treatment. • Poor 
prognosis for normal pregnancy with severe CEH. • Fair prognosis for successful 
pregnancy with treatment for primary 
hypoluteoidism; significant monitoring 
required for good outcome. • Pregnancy loss 
due to genetic abnormalities likely to recur if 
queen is bred to tom with similar pedigree.
ASSOCIATED CONDITIONS
Severe systemic disease otf any kind, 
malnutrition.
AGE-RELATED FACTORS
Queens >6 years old—higher incidence of 
lower litter size and infertility.
ZOONOTIC POTENTIAL
T. gondii .
PREGNANCY/FERTILITY/BREEDING
Queens with previous pregnancy loss are at 
higher risk of subsequent pregnancy loss or 
infertility and should be monitored inten- 
sively.
SYNONYMS
• Pregnancy loss. • Abortion. • Fetal 
mummification. • Early embryonic loss.
SEE ALSO
• Breeding, Timing.
• Sexual Development Disorders.
• CEH = cystic endometrial hyperplasia.
• COI = coefficient of inbreeding.
• FeLV = feline leukemia virus.
• FHV-1 = feline herpesvirus 1.
• FIPV = feline infectious peritonitis virus.
• FIV = feline immuno  deficiency virus.
• FPLV = feline panleukopenia virus.
• IFA = indirect fluorescent antibody.
• OHE = ovariohysterectomy.
• PGF2α = prostaglandin F2α.
Lamm CG. Clinical approach to abortion, 
stillbirth, and neonatal death in dogs and 
cats. Vet Clin North Am Small Anim Pract 
2012, (42)3:501–513.
Verstegen J, Dhaliwal G, Verstegen-Onclin K. 
Canine and feline pregnancy loss due to 
viral and non-infectious causes: a review. 
Theriogenology 2008, 70(3):304–319.
Author  Aime K. Johnson
Consulting Editor  Erin E. Runcan
Acknowledgment  The author and editors 
acknowledge the prior contribution of Milan 
Hess.
  Client Education Handout 
available online(continued)  Abortion, Spontaneous (Early Pregnancy Loss)—Cats

4 Blackwell’s Five-Minute Veterinary Consult  
AAbortion, Spontaneous (Early Pregnancy Loss)—Dogs
  BASICS
Loss of a fetus because of resorption in early 
stages or expulsion in later stages of pregnancy.
• Direct—congenital abnormality, infectious 
disease, trauma.
• Indirect—infectious placentitis, abnormal 
ovarian function, abnormal uterine environ- 
ment.
• Reproductive.
• Any major body system dysfunction can 
adversely affect pregnancy.
GENETICS
• No genetic basis for most causes.
• Lymphocytic hypothyroidism—single-gene 
recessive trait in Borzois.
• T rue incidence unknown.
• Resorption estimated between 11% and 
13%, up to 30% (at least one resorption).
• Incidence of stillbirth 2.2–4.4%; with 
dystocia up to 22.3%.
Species
Dog
Breed Predilections
• Familial lymphocytic hypothyroidism 
(Borzoi)—prolonged interestrus interval, 
poor conception rate, mid-gestation abortion, 
stillbirths.
• Many breeds at risk for hypothyroidism, 
although evidence of role in abortion unclear.
Mean Age and Range
• Infectious causes, pharmacologic agents 
causing abortion, fetal defects—all ages.
• Cystic endometrial hyperplasia—usually >6 
years old.
Predominant Sex
Intact bitches.
SIGNS
• Failure to whelp on time.
• Expulsion of recognizable fetuses or 
placental tissues.
• Decrease in abdominal size; weight loss.
• Anorexia, vomiting, diarrhea.
• Behavioral changes.
• Sanguineous or purulent vulvar discharge.
• Disappearance of previously documented 
vesicles or fetuses.
• Abdominal straining, discomfort.
• Depression.
• Dehydration.
• Fever.CAUSES
• Brucella canis .
• Canine herpesvirus.
• Toxoplasma gondii , Neospora caninum .
• Mycoplasma  and Ureaplasma .
• Bacteria— Escherichia coli , Streptococcus , 
Campylobacter , Salmonella .
• Viruses—distemper, parvovirus, adenovirus.
Uterine
• Cystic endometrial hyperplasia and pyometra.
• T rauma—acute and chronic.
• Neoplasia.
Ovarian
• Hypoluteoidism—abnormal luteal function 
in absence of fetal, uterine, or placental 
disease: progesterone concentrations <1–2 ng/
mL, most commonly 40–45 days’ gestation.
Exogenous Administration
• Embryotoxic drugs.
• Chemotherapeutic agents.
• Estrogens.
• Glucocorticoids.
• Prostaglandins—lysis of corpora lutea.
• Dopamine agonists—lysis of corpora lutea 
via suppression of prolactin; bromocriptine, 
cabergoline.
Hormonal Dysfunction
• Hypothyroidism (less common).
• Hyperadrenocorticism.
• Endocrine-disrupting contaminants 
documented in human and wildlife fetal loss.
Fetal Defects
• Lethal chromosomal abnormality or organ 
defects.
• Exposure of brood bitch to carrier animals.
• Old age.
• Hereditary factors.
  DIAGNOSIS
• Differentiate infectious from noninfectious 
causes— B. canis  immediate and zoonotic 
concern.
• Differentiate resorption from infertility—
helped by early diagnosis of pregnancy.
• History of drug use during pregnancy—
particularly during first trimester, or use of 
drugs (e.g., dexamethasone, prostaglandins, 
ketoconazole, griseofulvin, doxycycline, 
tetracycline, dantrolene) known to cause fetal 
death.
• Vulvar discharge during diestrus—may 
mimic abortion; evaluate discharge and origin 
to differentiate uterine from distal reproduc -
tive tract disease.• Necropsy of aborted fetus, stillborn puppies, 
and placenta(s)—enhance chances of 
definitive diagnosis.
• Systemic or endocrine disease—problems 
with maternal environment.
• Usually normal.
• Systemic disease, uterine infection, viral 
infection, or endocrine abnormalities—may 
produce changes in CBC, biochemistries, or 
urinalysis.
• Serologic testing— B. canis , canine 
herpesvirus, Toxoplasma , Neospora ; collect 
serum as soon as possible after abortion; 
repeat testing for paired titers for canine 
herpesvirus, Toxoplasma , Neospora .
• B. canis—
◦ Slide test (D-Tec CB®, Zoetis) very 
sensitive; negative results reliable; 
prevalence of false positives as high as 60%.
◦ PCR best to use on abortive discharge 
(Kansas State Veterinary Diagnostic 
Laboratory).
◦ Definitive diagnosis made via culture of 
abortive discharge or dam serum.
◦ T ube agglutination—titers >1 : 200 
considered positive; titers 1 : 50–1 : 200 
suspicious.
◦ Agar gel immunodiffusion—differen -
tiates between false positives and true 
positives in agglutination tests; detects 
cytoplasmic and cell surface antigens.
• Baseline T4 serum concentration—
hypothyroidism possible cause for fetal 
wastage; role in pregnancy loss unclear.
• Serum progesterone concentration 
(hypoluteoidism; if no infectious cause); dogs 
depend on ovarian progesterone production 
throughout gestation (minimum of 2 ng/mL 
required to maintain pregnancy); determine 
as soon as possible after abortion; in 
subsequent pregnancies, start weekly 
monitoring at week 3 (may be before 
pregnancy documented with ultrasound); 
start biweekly sampling around gestational 
age of prior loss. Pregnancy loss typically 
occurs during seventh week of gestation (see 
Premature Labor).
• Vaginal culture— B. canis  with positive 
serologic test; Mycoplasma , Ureaplasma , other 
bacterial agents; all except B. canis  can be 
normal flora, so diagnosis difficult from 
vaginal culture alone; limited benefit unless 
heavy growth of single organism; Salmonella  
associated with systemic illness.
IMAGING
• Radiography—identifies fetal structures 
after 45 days of gestation; earlier determines 
uterine enlargement but not uterine contents.
• Ultrasonography—identify uterine size and 
contents; assess fluid and its consistency; 
assess fetal viability (heartbeats: normal, 
>200 bpm; stress, <150 or >280 bpm).

Canine and Feline, Seventh Edition  5
A
• Vaginoscopy—identify source of vulvar 
discharge and vaginal lesions; use scope of 
sufficient length (16–20 cm) to examine 
entire length of vagina.
• Cytologic examination, bacterial culture—
may reveal inflammatory process (e.g., uterine 
infection): use guarded swab to ensure anterior 
sample (distal reproductive tract is heavily 
contaminated with bacteria), or collect 
secretions by transcervical catheterization.
Histopathologic examination and culture of 
fetal and placental tissue—may reveal 
infectious organisms; tissue culture, particu-
larly of stomach contents, may identify 
infectious bacteria.
  TREATMENT
• Most bitches should be isolated pending 
diagnosis.
• Hospitalization of infectious patients 
preferred.
• B. canis— highly infective; shed in high 
numbers during abortion; suspected dogs 
should be isolated.
• Outpatient—medically stable patients with 
noninfectious pregnancy loss.
• Partial abortion—attempt to salvage live 
fetuses; antibiotics indicated if bacterial 
component.
Dehydration—isotonic crystalloid fluids, 
electrolyte supplementation as indicated.
ACTIVITY
Partial abortion—cage rest, but effect on 
reducing further abortion unknown.
DIET
No special considerations; abortions have 
been associated with raw diets.
• Critical for B. canis —if confirmed, euthanasia 
recommended due to lack of successful 
treatment and to prevent spread; may try 
ovariohysterectomy (OHE) and long-term 
antibiotics with surveillance program for kennel 
situations (monthly serology, culling any 
positive animals until three consecutive negative 
tests are obtained); discuss zoonotic potential.
• Primary uterine disease—OHE is indicated 
in nonbreeding patients; cystic endometrial 
hyperplasia (CEH) is irreversible.
• Infertility or pregnancy loss—may recur in 
subsequent estrous cycles despite successful 
immediate treatment; pedigree analysis may 
be beneficial in highly linebred animals if 
pregnancy loss and small litter size due to 
inbreeding depression.• Prostaglandin treatment—discuss side 
effects (e.g., abortion).
• Infectious disease—establish surveillance 
and control measures.
OHE preferred for stable nonbreeding patients.
• Prostaglandin F2 α (PGF2α; Lutalyse®, dinoprost 
tromethamine)—uterine evacuation after 
abortion; 0.05–0.1 mg/kg SC q8–24h; 
cloprostenol (Estrumate®, cloprostenol)—1–5  μg/
kg SC q24h; not approved for use in dogs, but 
adequate documentation for use; use only if all 
living fetuses expelled.
• Antibiotics—broad-spectrum agent 
appropriate pending culture and sensitivity of 
vaginal tissue or fetus.
• Progesterone (altrenogest) at 0.088 mg/kg 
(1 mL/25 kg PO q24h); progesterone in oil 
at  2 mg/kg IM q48–72h; progesterone 
(Prometrium®; 10 mg/kg PO q24h, adjust 
daily dosage based on serum progesterone)—
for documented hypoluteoidism only to 
maintain pregnancy; must have accurate due 
date to know when to discontinue therapy; 
inadvertently prolonging gestation results in 
fetal death.
Progestogen supplementation contraindicated 
with endometrial or mammary gland disease.
• PGF2α—dose-related side effects related to 
smooth muscle contraction, diminish with 
each injection; panting, salivation, vomiting, 
and defecation common; caution in brachyce -
phalics; dosing critical (LD50 for 
dinoprost—5 mg/kg).
• Progesterone supplementation will prevent 
whelping—administration needs to be 
discontinued before 2–3 days prior to due 
date; risk of masculinization of female fetuses 
if used before day 45 of gestation.
Oxytocin—1 U/5 kg SC q6–24h for uterine 
evacuation; consider only where uterine 
evacuation solely through uterine contraction 
desired.
  FOLLOW-UP
• Partial abortion—monitor viability of 
remaining fetuses with ultrasonography; monitor 
systemic health of dam for rest of pregnancy.
• Vulvar discharges—daily; for decreasing 
amount, odor, and inflammatory component; for consistency (increasing mucoid content 
prognostically good).
• PGF2α—continued for 5 days or until most 
of discharge ceases (range 3–15 days).
• B. canis —monitor after neutering and 
antibiotic therapy; yearly serologic testing 
(identify recrudescence).
• Hypothyroidism—see Hypothyroidism.
• Brucellosis, other infectious agents—
surveillance programs to prevent spread to 
kennel.
• OHE—for nonbreeding bitches.
• Use of modified-live vaccines (e.g., some 
distemper, parvovirus), currently unavailable 
in United States.
• Untreated pyometra—septicemia, death.
• Brucellosis—discospondylitis, endophthal -
mitis, uveitis, zoonotic.
• Pyometra—recurrence during subsequent 
cycle likely (up to 70%) unless pregnant.
• CEH—recovery of fertility unlikely; 
pyometra common complication.
• Hormonal dysfunction—manageable; 
heritability should be considered.
• Brucellosis—guarded; extremely difficult to 
eliminate infection even with neutering.
Older bitches more likely to have CEH.
B. canis —can be transmitted to humans 
(especially if immunosuppressed), particularly 
when handling bitch and expelled tissues. 
Notify pathologists if B. canis  is suspected.
SEE ALSO
• Brucellosis.
• Hypothyroidism.
• Infertility, Female—Dogs.
• Premature Labor.
• Pyometra.
Author  Julie T. Cecere
available online(continued)  Abortion, Spontaneous (Early Pregnancy Loss)—Dogs

6 Blackwell’s Five-Minute Veterinary Consult  
AAbortion, Termination of Pregnancy
  BASICS
Termination of an unwanted pregnancy. May be 
accomplished by drugs that alter embryo 
transport in the oviduct, impeding establishment 
of a pregnancy, and/or cause luteal regression, 
terminating an established pregnancy. Due to 
their possible side effects (cystic endometrial 
hyperplasia, aplastic anemia, and bone marrow 
suppression), drugs that impair embryonic 
transit through the oviduct (estrogens) are not 
commonly used or recommended.
After fertilization the embryo travels the 
oviduct in a timely manner before entering the 
uterus. Impaired embryo transport through 
the oviduct leads to embryonic degeneration 
and implantation abnormalities. In the dog 
and cat, pregnancy maintenance is dependent 
on progesterone production from the corpora 
lutea. In dogs and cats, maintenance of the 
corpora lutea during the second half of 
gestation is also supported by prolactin (PRL). 
Drugs that cause luteal regression, antagonize 
PRL, and/or compete with progesterone 
receptors will terminate pregnancy.
• Cardiovascular.
• Digestive.
• Neurologic (caused by drugs used for 
treatment).
• Respiratory.
GENETICS
N/A
N/A
N/A
Species
Dog and cat.
N/A
Postpubertal bitch and queen.
Female
SIGNS
• Depends on stage of gestation:
◦ None.
◦ Vaginal discharge.
◦ Fetal expulsion.
CAUSES
• Impaired oviductal transport.
• Luteal regression.
• Progesterone receptor antagonism.RISK FACTORS
N/A
  DIAGNOSIS
• Confirm pregnancy first, ~60% of 
mismated bitches do not become pregnant:
◦ Abdominal palpation—bitch: 31–33 days 
after luteinizing hormone (LH) surge; 
queen: 21–25 days after breeding.
◦ T ransabdominal ultrasound—bitch: >25 days 
after LH surge; queen: >16 days after breeding.
◦ Abdominal radiographs—bitch: >45 days 
after LH surge; queen: >38 days after breeding.
◦ Serum relaxin concentration in the bitch 
(>28 days after LH surge; Witness® Relaxin, 
Synbiotics/Zoetis).
• Hydrometra.
• Mucometra.
• Hematometra.
• Pseudopregnancy.
• Within normal limits during first half of 
pregnancy in healthy patients.
• Decrease in hematocrit during second half 
of pregnancy in bitches and queens is normal.
• Recommended as screening tests prior to 
treatment in patients with suspected under  - 
lying disease.
• Vaginal cytology—determines stage of 
estrous cycle and presence of sperm (absence 
does not rule out previous breeding).
• Serum progesterone concentration deter  - 
mines if female in diestrus and monitors 
luteal regression during treatment.
IMAGING
• T ransabdominal ultrasound (method of 
choice)—diagnose pregnancy and monitor 
uterine evacuation during treatment.
• Abdominal radiographs.
N/A
N/A
  TREATMENT
• Physical examination before initiation of 
treatment.
• Monitor 30–60 minutes after treatment for 
side effects (vomiting, defecation, hypersaliva-
tion, hyperpnea, micturition, tachycardia).
• Pregnancy status in early diestrus is unknown; 
ultrasound confirmation of pregnancy not 
possible until ~4 weeks after breeding.• T reatment on day 6–10 of diestrus—may 
have reduced efficacy compared to mid-gesta-
tion, but can be less distasteful to client (less 
discharge and recognizable fetuses are not 
passed).
• Multimodal treatment improves efficacy of 
drugs given alone.
N/A
ACTIVITY
Normal
DIET
Avoid feeding prior to each treatment and for 
1–2 hours after treatments (reduces nausea 
and vomiting).
• Discuss patient’s reproductive future with 
owner. If no litters are desired, then ovario -
hysterectomy (OHE) is the best option.
• Discuss with client potential side effects of 
treatment options; reach mutual agreement 
on treatment plan.
OHE recommended for patients with no 
reproductive value or when owners do not 
desire future litters.
• Confirmation of pregnancy before initiating 
any of treatment protocols suggested below is 
recommended. Duration of suggested 
treatment may vary; treatments should be 
continued until abortion is complete.
• Prostaglandin F2α (PGF2α)—causes luteal 
regression with subsequent decline in 
progesterone concentration, cervical relax  - 
ation, and uterine contractions. Higher doses 
necessary prior to day 28 of gestation.
◦ Bitch low dose protocol—10  μg/kg SC q6h 
for 7–10 days or until pregnancy termination.
◦ Bitch standard dose protocol—100  μg/kg 
SC q8h for 2 days, then 200  μg/kg SC q8h 
until pregnancy termination.
◦ Queen low dose protocol—25  μg/kg SC 
q6h for 1–2 days, then 50  μg/kg SC q6h for 
3–4 days (queen more resistant to luteolytic 
effects of PGF2α than bitches; often higher 
doses for longer periods are required).
◦ Queen standard protocol—0.5–1 mg/kg 
SC q12h every other day ( >day 40), or 
2 mg/cat SC q24h for 5 days ( >day 33).
• Cloprostenol (prostaglandin analogue):
◦ Bitch—2.5  μg/kg SC q8–12h every 48 
hours until pregnancy termination ( ~6 days 
after start of treatment).
• Dexamethasone—mode of action 
unknown:
◦ Bitch—0.2 mg/kg PO q8–12h for 5 
days, then decreasing incrementally from

Canine and Feline, Seventh Edition  7
A
0.16 to 0.02 mg/kg over last 5 days; 
treatment failures not uncommon.
• Cabergoline (PRL antagonist)—causes 
luteal regression:
◦ Bitch—1.65  μg/kg SC q24h for 5 days or 
5 μg/kg PO q24h for 5 days ( >day 40).
◦ Queen—1.65  μg/kg SC for 5 days ( >day 30) 
or 5 μg/kg PO q24h for 5 days ( >day 35).
• Bromocriptine (PRL antagonist)—causes 
◦ Bitch—50–100  μg/kg IM/PO q12h for 
4–7 days >day 35 (50% effective); common 
side effect vomiting; reduce dose and give 
with meal.
• Cloprostenol and cabergoline combination:
◦ Bitch—cabergoline 5  μg/kg PO q24h for 
10 days plus cloprostenol 2.5  μg/kg SC at 
start of treatment or 1  μg/kg SC at start of 
treatment and at day 5 of treatment; 
treatment should be initiated >28 days 
post-LH surge.
◦ Queen—cabergoline 5  μg/kg PO q24h 
plus cloprostenol 5  μg/kg SC q48h ( >30 
days after breeding) until abortion 
complete ( ~9 days).
• Cloprostenol and bromocriptine 
combination:
◦ Bitch—bromocriptine 30  μg/kg PO q8h 
for 10 days plus cloprostenol 2.5  μg/kg SC 
or 1 μg/kg SC at start of treatment and at 
day 5 of treatment; treatment should be 
initiated >28 days post-LH surge.
• PGF2α and analogues—animals with 
respiratory disease (bronchoconstriction); do 
not administer intravenously. Use with 
caution in brachycephalic breeds.
• Cabergoline and bromocriptine—avoid 
administration in animals hypersensitive to 
ergot alkaloids; use with caution in patients 
with impaired liver function.
• Estrogens may cause cystic endometrial 
hyperplasia (CEH), pyometra, and bone 
marrow suppression leading to pancytopenia.
• PGF2α and analogues—side effects dose 
dependent and include vomiting, defecation, 
dyspnea, tachycardia, salivation, restlessness, 
and anxiety; side effects subside within 60 
minutes; use extreme caution in dogs and cats 
with preexisting cardiopulmonary, liver, and 
renal diseases.
• Dexamethasone—polydipsia, polyuria, and 
polyphagia are reported side effects; long-
term administration can result in signs of 
hyperadrenocorticism.
• Cabergoline and bromocriptine—should be 
administered with caution in patients with impaired liver function; side effects may 
include vomiting and anorexia; prolonged use 
(>2 weeks) may cause coat color changes.
• PGF2α and analogues—effect may be reduced 
by concomitant administration of progestins; 
use may enhance effects of oxytocin.
• Cabergoline and bromocriptine—cabergo-
line effects may be reduced with concomitant 
treatment with dopamine (D2) antagonists; 
avoid concomitant treatment with drugs 
causing hypotension.
• The following drugs are recommended for 
use in bitches but are not readily available in 
the United States:
◦ Aglepristone (progestin and glucocorticoid 
receptors antagonist)—10 mg/kg SC q24h 
for 2 days >14 days post-LH surge; highly 
effective in preventing pregnancy (>95% 
treatment efficacy); abdominal ultrasound 
at 28–30 days essential to insure treatment 
success; if pregnancy still present, repeat 
injection protocol. Mild reactions at 
injection site have been reported; mild 
vaginal discharge may be observed; slight 
risk (3.4%) of development of pyometra in 
field studies.
◦ Aglepristone and cloprostenol combina -
tion—aglepristone (10 mg/kg SC) combined 
with cloprostenol (1  μg/kg SC) q24h for 2 
days >25 days’ pregnancy; pregnancy 
terminated within 6 days. Side effects after 
treatment include vomiting and diarrhea; 
vaginal discharge may be observed.
◦ Aglepristone (10 mg/kg SC q24h for 
2 days) with intravaginal misoprostol 
(200–400  μg depending on body size) daily 
until abortion complete; abortion complete 
within 7 days. Vomiting, diarrhea, polydip -
sia, anorexia not observed with this regimen.
  FOLLOW-UP
In animals treated with luteolytic drugs 
(prostaglandins and PRL antagonists), 
progesterone assays and transabdominal 
ultrasound examinations should be performed 
to monitor decrease of serum progesterone 
concentration and complete evacuation of 
uterine contents. In patients treated with 
progesterone receptor antagonist drugs, 
transabdominal ultrasound examinations are 
recommended to monitor complete evacu -
ation of the uterus.PREVENTION/AVOIDANCE
• OHE for bitches and queens not intended 
for breeding.
• Estrus suppression or confinement of 
bitches and queens intended for breeding 
during a later cycle to avoid mismating.
Pregnancy termination may not be achieved after 
one treatment protocol and continuation or 
change in treatment protocol may be necessary.
• Interestrous interval in bitches treated with 
prostaglandins and PRL inhibitors may be 
shortened ( ~1 month). Queens may resume 
estrous behavior 7–10 days after pregnancy 
termination.
• Subsequent estrus fertility not affected.
N/A
N/A
N/A
N/A
SYNONYMS
Induced abortion.
SEE ALSO
Breeding, Timing.
• LH = luteinizing hormone.
• PRL = prolactin.
Eilts BE. Pregnancy termination in the bitch 
and queen. Clin Tech Small Anim Pract 
2002, 17:116–123.
Fieni F , Dumon C, Tainturier D, Bruyas JF . 
Clinical protocol for pregnancy termination 
in bitches using prostaglandin F2α. J Reprod 
Fertil Suppl 1997, 51:245–250.
Author  Jose A. Len
available online(continued)  Abortion, Termination of Pregnancy

8 Blackwell’s Five-Minute Veterinary Consult  
AAbscessation
  BASICS
An abscess is a focal collection of purulent 
exudate within a confined tissue space or cavity.
• Bacterial organisms may enter tissue by 
penetrating trauma, spread from another 
source of infection (hematogenous or 
adjacent infected tissues), or migration of a 
contaminated object (e.g., plant awn).
• Most often, bacteria are inoculated under 
the skin via puncture or bite wounds.
• When bacteria or foreign objects persist in 
tissue, purulent exudate accumulates.
• If exudate not quickly resorbed or drained, 
fibrous capsule forms to “wall off” infection; 
abscess may eventually rupture.
• With fibrous capsule—to heal, the cavity 
must fill with granulation tissue from which 
causative agent may not be totally eliminated; 
may lead to chronic or intermittent discharge 
of exudate from a draining tract.
• Sterile abscesses can occur when irritants 
(injectable medications, venom) or inflamm­
atory processes (pancreatitis, immune 
mediated, decreased blood supply) lead to 
local collection of purulent exudate.
• Skin/exocrine—percutaneous (cats > dogs); 
anal sac (dogs > cats).
• Reproductive—prostate gland (dogs > cats); 
mammary gland.
• Ophthalmic—periorbital tissues.
• Hepatobiliary—liver parenchyma.
• Gastrointestinal—pancreas (dogs > cats).
• Respiratory—pulmonary parenchyma.
GENETICS
N/A
N/A
N/A
Species
Cat and dog.
N/A
N/A
Mammary glands (female); prostate gland (male).
SIGNS
• Determined by organ system and/or tissue 
affected.
• Associated with combination of inflamm­
ation (pain, swelling, redness, heat, and loss of function), tissue destruction,  
and/or organ system dysfunction caused by 
accumulation of exudates.
• Often nonspecific signs (e.g., lethargy, 
anorexia).
• History of trauma or prior infection.
• Rapidly appearing painful swelling with or 
without discharge, if affected area is visible.
• Determined by organ system or tissue 
affected.
• Classic signs of inflammation (heat, pain, 
swelling, and loss of function) associated with 
specific anatomic location of abscess.
• Inflammation and discharge from fistulous 
tract may be visible if abscess has ruptured to 
an external surface.
• Variably sized, painful mass of fluctuant to 
firm consistency attached to surrounding 
tissues.
• Fever common, but may be absent if 
abscess has ruptured.
• Sepsis or infection of body cavity (e.g., 
pyothorax) may be seen if abscess ruptures 
internally.
CAUSES
• Foreign objects.
• Pyogenic bacteria— Staphylococcus  spp., 
Escherichia coli , β­hemolytic Streptococcus  
spp., Pseudomonas , Mycoplasma  and 
Mycoplasma ­like organisms (l ­forms), 
Pasteurella multocida , Corynebacterium , 
Actinomyces  spp., Nocardia , Bartonella .
• Obligate anaerobes— Bacteroides  spp., 
Clostridium  spp., Peptostreptococcus , 
Fusobacterium .
• Noninfectious—pancreatitis, suture 
reaction, vaccination, other injectable drug 
administration, stinging insects, snake 
envenomation, immune ­mediated panniculitis, 
dermatitis, neoplasia (especially when blood 
supply outgrown).
• Anal sac—impaction, anal sacculitis.
• Brain—otitis interna, sinusitis, oral 
infection.
• Liver—omphalophlebitis, sepsis.
• Lung—foreign object aspiration or 
migration, bacterial pneumonia.
• Mammary gland—mastitis.
• Periorbital—dental disease, chewing of 
wood or other plant material.
• Percutaneous—fighting, trauma, or 
surgery.
• Prostate gland—bacterial prostatitis.
• Immunosuppression—feline leukemia virus 
(FeLV) or feline immunodeficiency virus 
(FIV) infection, immunosuppressive chemo  ­ 
therapy, acquired or inherited immune system 
dysfunctions, underlying predisposing disease 
(e.g., diabetes mellitus, chronic renal failure, 
hyperadrenocorticism).  DIAGNOSIS
Mass Lesions
• Cyst—transiently painful, slower growing, 
no overt signs of inflammation.
• Fibrous scar tissue—firm, nonpainful.
• Granuloma—less painful, slower growing, 
firmer without fluctuant center.
• Hematoma/seroma—variable pain, 
nonencapsulated, rapid initial growth but 
slows once full size attained, fluctuant 
initially, may become more firm over time.
• Neoplasia—variable growth, variable pain.
Draining Tracts
• Fungal infection—blastomycosis, 
coccidioidomycosis, cryptococcosis, 
histoplasmosis, sporotrichosis.
• Mycobacterial disease.
• Mycetoma—botryomycosis, actinomycotic 
mycetoma, eumycotic mycetoma.
• Phaeohyphomycosis.
• CBC—normal, neutrophilia with or 
without left shift, neutropenia and 
degenerative left shift (severe infection).
• Serum chemistry profile—depends on 
severity, system affected. Signs of cholestasis if 
pancreatic abscess causes obstruction, 
hyperglycemia if diabetes mellitus, etc.
• Urinalysis—pyuria (prostatic abscess).
• FeLV, FIV testing—recurrent or slow ­
healing abscesses (cats).
• Cerebrospinal fluid evaluation—increased 
cellularity and protein with brain abscess.
• Adrenal function—hyperadrenocorticism.
IMAGING
• Radiography—soft ­tissue density mass in 
affected area, may reveal foreign material.
• Ultrasonography—determine if mass is 
fluid filled; may reveal foreign object; 
echogenic fluid suggests purulent exudate.
• Echocardiography—pericardial abscess, 
endocarditis.
• CT or MRI—pulmonary or brain abscess.
Fine-Needle Aspiration
• Red, white, yellow, or greenish liquid.
• Protein content >2.5–3.0 g/dL.
• Nucleated cell count—3,000–100,000 (or 
more) cells/ μL; primarily degenerate 
neutrophils, fewer macrophages, 
lymphocytes.
• Bacteria—intra ­ and extracellular:
◦ Gram stain to classify organism for 
empiric therapy.
◦ If causative agent not readily identified 
with a Romanowsky ­type stain, acid ­fast

Canine and Feline, Seventh Edition  9
A
stain to detect mycobacteria or Nocardia  and 
periodic acid ­Schiff stain to detect fungus.
Biopsy
• Sample should contain both normal and 
abnormal tissue.
• Impression smears.
• Tissue—for histopathologic examination 
and culture.
• Necessary to confirm nodular panniculitis.
Culture and Susceptibility Testing
• Affected tissue and/or exudate—aerobic 
and anaerobic bacterial and fungal.
• Blood and/or urine if systemic disease.
• Exudate ­containing mass lesion accom­
panied by inflammation.
• Causative agent may be detectable.
  TREATMENT
• Establish and maintain adequate drainage.
• Surgical removal of nidus of infection or 
foreign object(s) if necessary.
• Initiate appropriate antimicrobial therapy.
• Outpatient—minor abscesses, localized 
infection, nodular panniculitis.
• Inpatient—sepsis or systemic inflammation, 
extensive surgical procedures, treatment 
requiring hospitalization.
• Depends on location of abscess.
• Apply hot packs to inflamed area as needed.
• Use protective bandaging, Elizabethan 
collar as needed.
• Accumulated exudate—surgical drainage, 
debridement of necrotic tissue.
• Sepsis, peritonitis, pyothorax—fluid 
therapy, antimicrobial therapy, intensive care.
ACTIVITY
Restrict until abscess has resolved and 
adequate healing occurs.
DIET
N/A
• Correct or prevent risk factors.
• Maintain adequate drainage and continue 
antimicrobial therapy for adequate period of time.
• Appropriate debridement and drainage—
may need to leave wound open to external 
surface; may need drain placement.
◦ Penrose drains must exit ventrally to 
encourage drainage; may be bandaged, if 
bandage is changed regularly.
◦ If no ventral drainage, use active drains 
(e.g., Jackson ­Pratt drain).• Early drainage—to prevent further tissue 
damage and abscess wall formation.
• Remove foreign objects(s), necrotic tissue, 
nidus of infection.
• Complications to discuss include progressive 
tissue damage, necrosis, dehiscence of wound, 
prolonged healing times in high ­motion areas 
(axillary, inguinal).
• Antimicrobial drugs that are effective against 
infectious agent and penetrate site of infection.
• Broad ­spectrum agent—bactericidal with 
both aerobic and anaerobic activity until 
results of culture and sensitivity are known; 
Gram stain of exudate may guide therapy.
◦ Dogs and cats—amoxicillin (22 mg/kg 
PO q12h); amoxicillin–clavulanic acid 
(22 mg/kg PO q12h); clindamycin 
(5–10 mg/kg PO q12h); trimethoprim–
sulfadiazine (15 mg/kg PO q12h).
◦ Cats only—pradofloxacin (7.5 mg/kg  
PO q24 for 7 days).
◦ Cats with Mycoplasma  and L ­forms—
doxycycline (5 mg/kg PO q12h).
• Aggressive IV antimicrobial therapy—
sepsis, peritonitis, pyothorax.
• Antimicrobials not required for confirmed 
sterile abscesses.
N/A
N/A
N/A
Sterile nodular panniculitis—corticosteroids.
  FOLLOW-UP
Monitor for progressive decrease in drainage, 
resolution of inflammation, and improvement 
of clinical signs.
• Percutaneous abscesses—prevent fighting; 
consider castration to reduce roaming or 
aggressive behavior.
• Anal sac abscesses—prevent impaction; 
consider anal saculectomy for recurrent cases.
• Prostatic abscesses—consider castration.
• Mastitis—prevent lactation (spay).
• Periorbital abscesses—do not allow chewing 
on foreign objects.POSSIBLE COMPLICATIONS
• Sepsis.
• Peritonitis/pleuritis if intra ­abdominal or 
intrathoracic abscess ruptures.
• Compromise of organ function.
• Delayed evacuation may lead to chronic, 
draining fistulous tracts.
Depends on cause, organ system involved, 
and amount of tissue destruction.
• FeLV or FIV infection.
• Immunosuppression.
N/A
• Mycobacteria and systemic fungal 
infections carry some potential.
• If prostatitis secondary to Brucella canis .
N/A
SEE ALSO
• Actinomycosis and Nocardia.
• Anaerobic Infections.
• Colibacillosis.
• Mycoplasmosis.
• Nocardiosis/Actinomycosis—Cutaneous.
• Sepsis and Bacteremia.
• FIV = feline immunodeficiency virus.
Green CE, Goldstein EJC. Bite wound 
infections. In: Greene CE, ed., Infectious 
Diseases of the Dog and Cat, 4th ed. St. 
Louis, MO: Elsevier Saunders, 2012, pp. 
528–542.
Singh A, Scott Weese J. Wound infections 
and antimicrobial use. In: Johnston SA, 
Tobias KM, eds., Veterinary Surgery Small 
Animal, 2nd ed. St. Louis, MO: Elsevier, 
2018, pp. 148–155.
Author  Selena Lane
Consulting Editor  Amie Koenig
acknowledge the prior contribution of Adam 
J. Birkenheuer.
available online(continued)  Abscessation

10 Blackwell’s Five-Minute Veterinary Consult  
AAcetaminophen (APAP) Toxicosis
  BASICS
Results from accidental animal ingestion or 
owner administration of over-the-counter 
acetaminophen-containing analgesic and 
antipyretic medications.
When the normal biotransformation 
mechanisms for detoxification (glucuronida-
tion and sulfation) are saturated, cytochrome 
P450–mediated oxidation produces a toxic 
metabolite ( N-acetyl-p-benzoquinone imine) 
that is electrophilic, conjugates with glutathione, 
and binds to sulfhydryl groups, leading to 
hepatic necrosis.
Dogs
• Liver is most susceptible to toxicity.
• Signs commonly observed at exposures 
>75–100 mg/kg.
• Methemoglobinemia may develop at doses 
>200 mg/kg.
Cats
• Cannot effectively glucuronidate; more 
limited capacity for acetaminophen 
elimination than dogs.
• Saturate glucuronidation and sulfation 
biotransformation routes.
• Red blood cells (RBCs) are most susceptible 
to oxidative injury following glutathione 
depletion.
• Develop toxic cytochrome P450 metabolite 
at much lower doses than dogs.
• Poisoned by as little as 50–60 mg/kg (often 
as little as one half tablet); deacetylation of 
acetaminophen to p-aminophenol (PAP) 
causes oxidative damage to RBCs, rapidly 
producing methemoglobinemia by binding to 
sulfhydryl groups on hemoglobin.
• Slower-developing hepatotoxicosis may not 
be fully expressed before development of fatal 
methemoglobinemia.
• Hemic/lymph/immune—RBCs damaged 
by glutathione depletion, allowing oxidation 
of hemoglobin to methemoglobin.
• Hepatobiliary—liver necrosis (more 
common in dogs).
• Cardiovascular (primarily cats)—edema of 
face, paws, and (to lesser degree) forelimbs 
through undefined mechanism.
GENETICS
Cats—genetic deficiency in the glucuronide 
conjugation pathway makes them vulnerable.
Common drug toxicity in cats; less frequent 
in dogs.
N/ASIGNALMENT
Species
Cats more often than dogs.
SIGNS
Relatively common—owing to widespread 
human use.
• Hyperventilation.
• Darkened mucous membranes.
• Signs may develop 1–4 hours after dosing.
• Progressive depression.
• Salivation.
• Vomiting.
• Abdominal pain.
• Tachypnea and cyanosis or muddy mucous 
membranes—reflect methemoglobinemia.
• Edema—face, paws, and possibly forelimbs; 
after several hours.
• Chocolate-colored urine—hematuria and 
methemoglobinuria; especially in cats.
• Icterus.
• Hypothermia.
• Shock.
• Death.
CAUSES
Acetaminophen toxicosis.
• Nutritional deficiencies of glucose and/or 
sulfate.
• Simultaneous administration of other 
glutathione-depressing drugs.
  DIAGNOSIS
Other Causes of Liver Injury
• Hepatotoxic mushrooms.
• Blue-green algae.
• Aflatoxins.
• Iron, copper, zinc.
• Xylitol.
• Cycad palms.
• Nonsteroidal anti-inflammatory drugs 
(NSAIDs).
Other Causes of Methemoglobinemia
• Onions/garlic.
• Naphthalene.
• Chlorates.
• Nitrites.
• Sulfites.
• Phenol.
• Benzocaine.
• Propylene glycol (cats).
• Methemoglobinemia and progressively 
rising serum concentrations of liver enzymes (alanine aminotransferase [ALT], aspartate 
transaminase [AST])—characteristic.
• As hepatic function becomes impaired—
decreased blood urea nitrogen (BUN), 
cholesterol, and albumin, and increased 
serum bilirubin.
• Heinz bodies (cats)—prominent in RBCs 
within 72 hours.
• Anemia, hemoglobinemia, and hemoglob -
inuria or hematuria.
Acetaminophen plasma, serum, or urine 
concentrations.
IMAGING
N/A
N/A
• Methemoglobinemia.
• Pulmonary edema.
• Centrilobular necrosis and congestion of 
the liver.
• Renal tubular edema and degeneration with 
proteinaceous tubular casts.
  TREATMENT
• With methemoglobinemia—must evaluate 
promptly.
• With dark or bloody colored urine or 
icterus—inpatient.
• Gentle handling—imperative for clinically 
affected patients.
• Induced emesis and gastric lavage—useful 
within 4–6 hours of ingestion.
• Anemia, hematuria, or hemoglobinuria—
may require whole blood transfusion.
• Fluid therapy—maintain hydration and 
electrolyte balance.
• Oxygen therapy may be needed.
• Drinking water—available at all times.
• Food—offered 24 hours after initiation of 
ACTIVITY
Restricted
DIET
N/A
• Warn client that treatment in clinically 
affected patients may be prolonged and 
expensive.
• Inform client that patients with liver injury 
may require prolonged and costly management.
N/A

Canine and Feline, Seventh Edition  11
A
• Activated charcoal 1–2 g/kg PO with a 
cathartic; immediately after completion of 
emesis or gastric lavage.
• N-acetylcysteine (Mucomyst ®) 140 mg/kg 
diluted in 5% dextrose injection (D5W) as 
loading dose PO/IV; then 70 mg/kg diluted 
in D5W PO/IV q6h for 7 additional treat- 
ments. Large overdoses may require up to 17 
treatments.
• S-adenosylmethionine (SAMe) as a 
glutathione donor; 40 mg/kg PO × 1 dose, 
then 20 mg/kg q24h PO × 7 days.
• Added benefit of using methylene blue, 
cimetidine, and/or ascorbic acid is contro- 
versial.
Drugs that contribute to methemoglobinemia 
or hepatotoxicity.
Drugs requiring extensive liver metabolism or 
biotransformation—use with caution; expect 
their half-lives to be extended.
Drugs requiring activation or metabolism by 
the liver have reduced effectiveness.
  FOLLOW-UP
• Continual clinical monitoring of methemo -
globinemia—vital for effective management; 
laboratory determination of methemoglobin 
percentage every 2–3 hours.
• Serum liver enzyme activities (ALT, ALP) 
every 12 hours; monitor liver damage.PREVENTION/AVOIDANCE
• Never give acetaminophen to cats.
• Give careful attention to acetaminophen 
dose in dogs.
Liver necrosis and resulting fibrosis—may 
compromise long-term liver function in 
recovered patients.
• Rapidly progressive methemoglobinemia—
serious sign.
• Methemoglobin concentrations ≥50%—
grave prognosis.
• Progressively rising serum liver enzymes 
12–24 hours after ingestion—serious concern.
• Expect clinical signs to persist 12–48 hours; 
death owing to methemoglobinemia possible 
at any time.
• Dogs and cats receiving prompt treatment 
that reverses methemoglobinemia and 
prevents excessive liver necrosis—may 
recover fully.
• Dogs—death as a result of liver necrosis 
may occur within 72 hours.
• Cats—death as a result of methemoglobine-
mia occurs 18–36 hours after ingestion.
Keratoconjunctivitis sicca may develop in 
small-breed dogs as a sequela.
Young and small dogs and cats—greater risk 
from owner-given single-dose acetaminophen 
medications.
Imposes additional stress and higher risk on 
exposed animals.SYNONYMS
• Paracetamol.
• Tylenol ®.
SEE ALSO
Poisoning (Intoxication) Therapy.
• ALT = alanine aminotransferase.
• AST = aspartate transaminase.
• BUN = blood urea nitrogen.
• D5W = 5% dextrose injection.
drug.
• PAP = p-aminophenol.
• RBC = red blood cell.
• SAMe = S-adenosylmethionine.
INTERNET RESOURCES
https://www.aspca.org/pet-care/
animal-poison-control
Plumb DC. Acetaminophen. In: Plumb DC, 
ed., Plumb’s Veterinary Drug Handbook, 
9th ed. Ames, IA: Wiley-Blackwell, 2018, 
pp. 6–8.
Plumlee KH. Hematic system. In: Plumlee 
KH, ed., Clinical Veterinary Toxicology. St. 
Louis, MO: Mosby, 2004, p. 59.
Schell MM, Gwaltney-Brant S. OTC drugs. 
In: Poppenga RH, Gwaltney-Brant SM, eds., 
Small Animal Toxicology Essentials. Chichester: 
Wiley-Blackwell, 2011, pp. 231–233.
Sellon RK. Acetaminophen. In: Peterson ME, 
Talcott PA, eds. Small Animal Toxicology, 
3rd ed. St. Louis, MO: Elsevier, 2013, pp. 
423–429.
Stockham SL, Scott MA. Fundamentals of 
Veterinary Clinical Pathology, 2nd ed. 
Oxford: Blackwell, 2008, p. 186.
Author  Lisa A. Murphy
available online(continued)  Acetaminophen (APAP) Toxicosis

12 Blackwell’s Five-Minute Veterinary Consult  
AAcidosis, Metabolic
  BASICS
A process in the body that leads to a decrease 
in pH below the reference interval. A decline 
in blood pH is specifically termed acidemia. 
Associated with a decrease in plasma bicarb  - 
onate concentration ( HCO3; dogs, 
<18 mEq/L; cats, <16 mEq/L) and base 
excess (BE; –4 mmol/L) with a compensatory 
decrease in carbon dioxide tension (PCO2).
• Metabolic acidosis may develop either from 
a loss of  HCO3 (hyperchloremic acidosis) or 
a gain in acid  (high anion gap [AG] acidosis). 
It is usually secondary to an accumulation of 
metabolically produced strong anions (strong 
ion gap or high anion gap acidosis), accumu-
lation of weak acids (hyperphosphatemia), 
corrected hyperchloremia (hyperchloremic 
acidosis), or as a compensatory mechanism 
for respiratory alkalosis.
• High anion gap  acidosis—increase in the 
concentration of other strong anions through 
addition (e.g., ethylene glycol toxicity), excessive 
production (e.g., lactate produced by prolonged 
anaerobic metabolism), or renal retention (e.g., 
renal failure) of strong anions other than Cl– 
causes metabolic acidosis without increasing 
Cl– concentration (so-called normochloremic or 
high AG metabolic acidosis).
• Hyperphosphatemic  acidosis—increase in 
plasma weak acids (e.g., inorganic phosphate) 
is associated with metabolic acidosis and 
increased AG. At a pH of 7.4, a 1 mg/dL 
increase in phosphate concentration is 
associated with a 0.58 mEq/L decrease in 
HCO3 and a 0.58 mEq/L increase in AG. 
Hyperphosphatemia commonly develops with 
decreased renal phosphorus excretion (e.g., 
renal failure, hypoparathyroidism), cellular 
lysis (e.g., tumor lysis syndrome, trauma, 
rhabdomyolysis), bone neoplasms (increased 
bone resorption), and hypervitaminosis D.
• Hyperchloremic  acidosis—may be caused by 
Cl– retention (e.g., renal failure, renal tubular 
acidosis) that typically occurs in response to 
HCO3 loss. Cl– and HCO3 are reciprocally 
related; loss of HCO3 generally results in 
retention of Cl–. Other mechanisms for hyper-  
chloremic acidosis include excessive loss of Na+ 
relative to Cl– (e.g., diarrhea, Addison’s) and 
administration of substances containing more 
Cl– than Na+ compared with normal extracel -
lular fluid composition (e.g., administration of 
KCl, 0.9% NaCl). Acidemia is usually not 
severe in patients with hyperchloremic acidosis.
• Cardiovascular—fall in pH results in increase 
in sympathetic discharge, but simultaneously 
causes decrease in responsiveness of cardiac 
myocytes and vascular smooth muscle to effects of catecholamines. In mildly acidemic 
conditions (pH >7.2), effects of increased 
sympathetic stimulation predominate and 
result in mild increase in heart rate and cardiac 
output. More severe acidemia (pH <7.1), 
especially if acute, may decrease cardiac 
contractility and predispose heart to ventricular 
arrhythmias and ventricular fibrillation.
• Respiratory—increased hydrogen ion [H+] 
stimulates peripheral and central chemorecep -
tors to increase alveolar ventilation; hyperven -
tilation decreases PCO2, which counters effects 
of low plasma HCO3 on pH. In dogs, a 
decrease of approximately 1 mmHg in PCO2 is 
expected for each 1 mEq/L decrease in plasma 
HCO3. Little known about compensation in 
cats, but appears to be almost nonexistent.
• Renal/urologic—kidneys increase net acid 
excretion, primarily by increasing excretion of 
NH4+ and Cl–. This compensatory mecha-
nism not very effective in cats.
Any breed, age, or sex of dog and cat.
SIGNS
Chronic disease processes that lead to 
metabolic acidosis (e.g., renal failure, diabetes 
mellitus, and hypoadrenocorticism), acute 
circulatory shock (hemorrhagic), exposure to 
toxins (e.g., ethylene glycol, salicylate, and 
paraldehyde), diarrhea, administration of 
carbonic anhydrase inhibitors (e.g., acetazola-
mide and dichlorphenamide).
PHYSICAL EXAMINATION FINDINGS
• Generally relate to underlying disease.
• Depression, stupor, seizures, and/or 
generalized muscle weakness in severely 
acidotic patients.
• Tachypnea in some patients results from 
compensatory increase in ventilation.
• Kussmaul’s respiration, typically seen in 
human beings with metabolic acidosis, not 
commonly observed in dogs and cats.
• Vomiting and/or diarrhea.
CAUSES
Associated with Hyperchloremia 
(Hyperchloremic Metabolic Acidosis)
• Renal—renal tubular acidosis; carbonic 
anhydrase inhibitors.
• Gastrointestinal—diarrhea.
• Other: Cl–-rich fluids (e.g., 0.9% NaCl, KCl 
supplementation); total parenteral nutrition 
with cationic amino acids: lysine, arginine, 
and histidine; rapid correction of hypocapnia 
(chronic respiratory alkalosis); NH4Cl or HCl.
Associated with Normochloremia (High 
Anion Gap Metabolic Acidosis)
• Renal—uremic acidosis, acute renal failure.
• Ketoacidosis—diabetic ketoacidosis, 
starvation, liver disease.
• Lactic acidosis—impaired perfusion, 
impaired carbohydrate metabolism.• Toxins—ethylene glycol, salicylate, 
paraldehyde, methanol intoxication.
• Hyperphosphatemia (see Hyperphos- 
phatemia)—raises AG. At a pH of 7.4, each 
1 mg/dL increase in phosphate concentration 
is associated with a 0.58 mEq/L increase in AG.
• Chronic renal failure, diabetes mellitus, and 
hypoadrenocorticism.
• Poor tissue perfusion or hypoxia—lactic 
acidosis.
• T umor lysis syndrome or osteosarcoma— 
hyperphosphatemia.
• T rauma, snake envenomation, or malignant 
hyperthermia—rhabdomyolysis.
  DIAGNOSIS
Low plasma HCO3 and hyperchloremia may 
also be compensatory in animals with chronic 
respiratory alkalosis, in which PCO2 is low 
and pH is high or near normal, despite 
decreased HCO3 and increase in Cl– concen-
tration. Blood gas determination is required 
to differentiate.
LABORATORY FINDINGS
Drugs That May Alter Laboratory Results
Potassium bromide measured as Cl– in most 
analyzers; administration artificially decreases 
AG.
Disorders That May Alter Laboratory 
Results
• Too much heparin ( >10% of sample) 
decreases HCO3.
• Blood samples stored at room temperature 
for >15 minutes have low pH because of 
increased PCO2.
• Hypoalbuminemia lowers AG; negative 
charges of albumin are main component of 
AG.
Valid if Run in Human Laboratory?
Yes
• Low total CO2—total CO2 in serum 
samples handled aerobically closely approxi-
mates serum HCO3 concentration; 
unfortunately, patients with chronic 
respiratory alkalosis also have low total CO2, 
and distinction cannot be made without 
blood gas analysis.
• Metabolic acidoses traditionally divided 
into hyperchloremic and high AG by means 
of AG. Anion gap, the difference between the 
measured cations and the measured anions, is 
calculated as AG = [Na+] – (HCO3 + [Cl–]) 
or AG = ([Na+] + [K+]) – ( HCO3 + [Cl–]), 
depending on preference of clinician or 
laboratory. Normal values with potassium 
included in calculation usually 12–24 mEq/L

Canine and Feline, Seventh Edition  13
A
in dogs and 13–27 mEq/L in cats. Negative 
charges of albumin are major contributors to 
normal AG; this should be taken into account 
when evaluating AG in patients with hypo  - 
albuminemia. At pH 7.4 in dogs, decrease 
of 1 g/dL in albumin associated with decrease 
of 4.1 mEq/L in AG.
• Normal AG (i.e., hyperchloremic metabolic 
acidosis).
• High AG (i.e., normochloremic metabolic 
• Hyperglycemia.
• Azotemia.
• Hyperphosphatemia.
• High lactate concentration.
• Hyperkalemia ( formulas to adjust potassium 
concentration based on pH changes should not 
be used ).
Blood gas analysis reveals low HCO3, low 
PCO2, and low pH.
None
TREATMENT
• Acid-base disturbances are secondary 
phenomena; successful resolution depends on 
diagnosis and treatment of underlying disease 
process.
• Restore blood volume and perfusion deficits 
before considering sodium bicarbonate 
(NaHCO3).
• T reat patients with blood pH ≤7.1 
aggressively while pursuing definitive 
• Discontinue drugs that may cause 
metabolic acidosis.
• Nursing care—isotonic, buffered  electrolyte 
solution is fluid of choice for patients with 
mild metabolic acidosis and normal liver 
function.
• NaHCO3 may help patients with hyper -
chloremic, hyperhosphatemic, or uremic 
acidosis, but not patients with lactic acidosis 
or diabetic ketoacidosis.
• NaHCO3 may be considered for alkaline 
diuresis in salicylate toxicity. ° Estimation of 
HCO3 dose—dogs, 0.3 × body weight (kg) 
× (21 – patient HCO3); cats, 0.3 × body 
weight (kg) × (19 – patient HCO3). Give 
half of this dose slowly IV and reevaluate 
blood gases before deciding on need for 
additional administration. Empirical dose of 
1–2 mEq/kg followed by reevaluation of 
blood gas status is safe in most patients. 
° Potential complications of NaHCO3 
administration—volume overload resulting 
from administered Na+, tetany from low 
ionized calcium concentration, increased affinity of hemoglobin for oxygen, paradoxi-
cal CNS acidosis, overshoot metabolic 
alkalosis, hypokalemia.
• Hyperchloremic acidosis—NaHCO3 
may be effective and considered whenever 
pH <7.1.
• Uremic acidosis—efficacy of NaHCO3 in 
acute therapy of uremic acidosis is related to 
shift of phosphate inside cells and consequent 
amelioration of hyperphosphatemic acidosis.
• Lactic acidosis—NaHCO3 increases lactate 
production and is of little to no value in lactic 
acidosis. Therapy should be directed at 
augmenting oxygen delivery to tissues and 
reestablishing cardiac output. Small titrated 
doses of NaHCO3 can be used as temporizing 
measure to maintain HCO3 above 5 mEq/L, 
if needed.
• Diabetic ketoacidosis—NaHCO3 adversely 
affects outcome in humans with diabetic 
ketoacidosis even when pH is <7.0. 
Administration of NaHCO3 to ketoacidotic 
patients cannot be recommended at any pH. 
Therapy should be direct at insulin and fluid 
administration. Reestablishing plasma volume 
and renal perfusion will allow kidneys to 
excrete ketoanions, replacing them with Cl–.
• Avoid NaHCO3 in patients with respiratory 
acidosis because it generates CO2.
• Patients with respiratory acidosis cannot 
adequately excrete CO2, and increased PCO2 
will further decrease pH.
• Avoid diuretics that act in distal nephron 
(e.g., spironolactone).
• Avoid carbonic anhydrase inhibitors (e.g., 
acetazolamide, dichlorphenamide).
• Avoid NaHCO3 in acute ( <10 mins) cardiac 
arrest as it may impair tissue oxygen unloading.
Use NaHCO3 cautiously in patients with 
congestive heart failure because Na+ load may 
cause decompensation of heart failure.
None
None
  FOLLOW-UP
Recheck acid-base status; frequency dictated 
by underlying disease and patient response to 
• Hyperkalemia in acute hyperchloremic 
acidosis.
• Myocardial depression and ventricular 
arrhythmias.  MISCELLANEOUS
• Hyperkalemia.
• Hyperchloremia.
None
N/A
SYNONYMS
• Dilutional acidosis—metabolic acidosis 
resulting from increased free water in plasma.
• Hyperchloremic acidosis—normal anion 
gap acidosis.
• Hyperphosphatemic acidosis—metabolic 
acidosis resulting from high phosphate 
concentration.
• Nonrespiratory acidosis.
• Normochloremic acidosis—high anion gap 
acidosis.
• Organic acidosis—metabolic acidosis 
resulting from accumulation of organic 
anions (e.g., ketoacidosis, uremic acidosis, 
and lactic acidosis).
SEE ALSO
• Azotemia and Uremia.
• Diabetes Mellitus With Ketoacidosis.
• Lactic Acidosis (Hyperlactatemia).
• AG= anion gap.
• BE = base excess.
• H+ = hydrogen ion.
• HCO3 = bicarbonate.
• NaHCO3 = sodium bicarbonate.
• PCO2 = carbon dioxide tension.
de Morais HA, Constable PD. Strong ion 
approach to acid-base disorders. In: 
DiBartola SP , ed., Fluid, Electrolyte and 
Acid-Base Disorders, 4th ed. St. Louis, MO: 
Saunders, 2012, pp. 316–330.
de Morais HA, Leisewitz AL. Mixed acid-base 
disorders. In: DiBartola SP , ed., Fluid, 
Electrolyte and Acid-Base Disorders, 4th ed. 
St. Louis, MO: Saunders, 2012, pp. 302–315.
DiBartola SP . Metabolic acid-base disorders. 
In: DiBartola SP , ed., Fluid, Electrolyte and 
Saunders, 2012, pp. 271–280.
Hopper K. T raditional acid-base analysis. In: 
Silverstein DC, Hopper K, eds., Small 
Animal Critical Care Medicine, 2nd ed. St. 
Louis, MO: Elsevier, 2015, pp. 289–299.
Author  Helio S. Autran de Morais
Consulting Editor  J.D. Foster
Acknowledgment  The author and book 
editor acknowledge the prior contribution of 
Lee E. Palmer.(continued)  Acidosis, Metabolic

14 Blackwell’s Five-Minute Veterinary Consult  
AAcne—Cats
  BASICS
OVERVIEW
• Inflammatory dermatitis affecting the chin 
and lips.
• Symptoms may be recurrent or persistent.
• Cats.
• Prevalence for sex, age, or breed not 
reported.
SIGNS
• Cats may have a single episode, a life-long 
recurrent problem, or a continual disease.
• Frequency and severity of each occurrence 
vary with the individual.
• Comedones, mild erythematous papules, 
serous crusts, and dark keratin debris develop 
on the chin and less commonly on the lips.
• Swelling of the chin.
• Severe cases—nodules, hemorrhagic crusts, 
pustules, cysts, fistulae, severe erythema, 
alopecia, and pain.
• Pain often associated with bacterial 
furunculosis.
Precise etiology unknown; often is associated 
with allergic skin diseases; may be a disorder 
of keratinization, poor grooming, abnormal 
sebum production, immunosuppression, viral 
infection, or stress.
  DIAGNOSIS
• Hypersensitivity (atopy, flea bite, food, 
contact).
• Bacterial folliculitis.
• Demodicosis.
• Malassezia  infection.
• Dermatophytosis.
• Neoplasia of sebaceous or apocrine glands.
• Eosinophilic granuloma.
N/A
N/A
IMAGING
N/A
• Skin scrapings—demodicosis.
• Bacterial culture—resistant infection.
• Fungal culture—dermatophytosis.
• Cytology—bacteria, Malassezia .
• Biopsy—rarely needed; necessary in 
selected cases to characterize changes such as 
cystic follicles, to differentiate acne from 
other diseases such as demodicosis, infections (bacterial, yeast, or dermatophytes), or to 
diagnose neoplasia.
• Mild disease—follicular distention with 
keratin (comedo), hyperkeratosis, and 
follicular plugging, most often associated 
with allergic dermatitis.
• Severe disease—mild to severe folliculitis 
and perifolliculitis with follicular pustule 
formation leading to furunculosis and 
pyogranulomatous dermatitis.
• Bacteria and Malassezia  in these lesions are 
considered secondary invaders and not 
causative agents.
• Demodex  mites can be primary agents of 
this disease.
  TREATMENT
• Initial treatment—gentle clipping and 
soakings to soften crusts.
• Food elimination diet.
• Intradermal allergy testing.
• Continue one or a combination of the 
therapies listed below until all lesions have 
resolved.
• Discontinue treatment by tapering 
medication over a 2- to 3-week period.
• Recurrent episodes—once the recurrence 
rate is determined, an appropriate maintenance 
protocol can be designed for each individual.
• Continual episodes—life-long maintenance 
treatment necessary.
Topical
• Shampoo—once or twice weekly with 
antiseborrheic (sulfur-salicylic acid, benzoyl 
peroxide, or ethyl lactate).
• Cleansing agents—benzoyl peroxide, salicylic 
acid, chlorhexidinephytosphingosine.
• Medicated wipes.
• Antibiotic ointment—mupirocin 2%.
• Other topicals—clindamycin or erythro -
mycin solution or ointment.
• Combination topicals—benzoyl peroxide-
antibiotic gels (e.g., Benzamycin).
• Topical retinoids—tretinoin (e.g., Retin-A® 
0.01%): gel more effective because of better 
penetration.
• In severe inflammatory periods 10–14 days 
of oral prednisolone (1–2  mg/kg q24h) may 
help to reduce scar tissue formation.
Systemic
• Antibiotics—amoxicillin with clavulanate, 
cephalosporin, or fluoroquinolone.• Severe cases may warrant treatment with 
isotretinoin (Accutane) or cyclosporine, 
modified (Atopica®).
• Demodicosis—isoxazoline parasiticides.
• Benzoyl peroxide and salicylic acids—can 
be irritating.
• Some wipes contain alcohols that can be 
irritating.
• Systemic isotretinoin—use with caution, if 
animal will not allow application of topical 
medications; potential deleterious side effects 
in human beings (drug interactions and 
teratogenicity); container should be labeled 
for animal use only and kept separate from 
human medications to avoid accidental use; 
currently difficult to obtain for animal 
patients.
  FOLLOW-UP
• Monitor for relapses.
• Maintenance cleansing programs can be 
used to reduce relapses; affected cats are likely 
to have variable numbers of comedones 
life-long, which often are just cosmetic, and 
treatment is not necessary.
Systemic isotretinoin should not be used on 
breeding animals.
Jazic E, Coyner KS, Loeffler DG, Lewis TP . 
An evaluation of the clinical, cytological, 
infectious and histopathological features of 
feline acne. Vet Dermatol 2006, 
17(2):134–140.
Miller WH, Griffin CE, Campbell KL. Acne. 
In: Muller & Kirk’s Small Animal 
Dermatology, 7th ed. St. Louis, MO: 
Elsevier, 2013, pp. 640–642.
Rosencrantz WS. The pathogenesis, 
diagnosis, and management of feline acne. 
Vet Med 1993, 5:504–512.
Werner AH, Power HT. Retinoids in 
veterinary dermatology. Clin Dermatol 
1994, 12(4):579–586.
White SD. Feline acne and results of 
treatment with mupirocin in an open 
clinical trial: 25 cases (1994–96). Vet 
Dermatol 1997, 8:157.
Author  David D. Duclos
Consulting Editor  Alexander H. Werner 
Resnick

Canine and Feline, Seventh Edition  15
A Acne—Dogs
  BASICS
OVERVIEW
• Also (more correctly) muzzle folliculitis and 
• Chronic inflammatory disorder of the chin 
and lips of mostly young animals.
• Characterized by folliculitis and furunculo-
sis; almost never comedogenic as seen in “true 
acneiform” lesions of human beings.
• Recognized almost exclusively in short-
coated breeds.
• Genetic predisposition, local trauma, and 
allergic disease often play a role.
• Dogs, often younger, sometimes puppies.
• Predisposed short-coated breeds—boxer, 
Doberman pinscher, English bulldog, Great 
Dane, Weimaraner, mastiff, Rottweiler, 
German shorthaired pointer, pit bull terrier.
SIGNS
• Ventral chin and lip margins may have few 
to numerous erythematous papules and 
sometimes bullae. These may coalesce to form 
plaques.
• Initial lesions are inflammatory and sterile; 
bacteria may not be isolated and lesions may 
not respond to antibiotics.
• Advanced lesions may contain pus or blood, 
indicating secondary deep bacterial folliculitis 
and furunculosis.
• Lesions may be pruritic, some are painful 
on palpation, but most are nonpainful and 
nonpruritic.
• Chronic and pruritic lesions may become 
hyperpigmented, lichenified, scarred, and 
alopecic.
Several short-coated breeds appear to be 
genetically predisposed to acne. Lesions may 
be worse in allergic individuals.
  DIAGNOSIS
• Juvenile cellulitis.
• Contact dermatitis.
• With other symptoms, consider allergic/
atopic disease as playing a role.
N/A
N/AIMAGING
N/A
• Impression cytology will help determine if 
bacteria or yeast are present.
• Skin scrape—demodicosis.
• Dermatophyte culture—dermatophytosis.
• Bacterial culture and sensitivity testing—in 
patients with suppurative folliculitis and 
furunculosis that are nonresponsive to initial 
antibiotic selection.
• Biopsy—histologic confirmation for cases 
in which diagnosis is in question.
• Clinical signs and histopathologic findings 
are diagnostic.
• Characterized histopathologically by 
folliculitis and furunculosis.
• Bacteria—not always isolated from lesions 
in early stages.
• As disease progresses, papules enlarge and 
rupture, promoting a suppurative folliculitis 
  TREATMENT
• Reduce behavioral trauma to the chin (e.g., 
rubbing on the carpet, chewing bones that 
increase salivation).
• Frequent cleaning with chlorhexidine-
containing pads, shampoos, or solutions can 
be helpful, but instruct owners not to scrub at 
the area.
• Gentamicin/steroid-containing ointments 
for the ears work well on the chin when 
applied twice daily.
• If topicals are not helpful by themselves, 
add oral antibiotics based on positive cytology 
and culture and sensitivity testing.
• Severe cases may necessitate short courses of 
oral steroids.
• Evaluate for underlying allergic/atopic 
disease and institute proper therapy for 
diagnosis and control of these diseases; control 
of allergic disease may permit resolution of 
muzzle folliculitis and furunculosis.
• Instruct owners to avoid squeezing the 
lesions; trauma may make inflammation 
worse.
DRUG(S)
Topical
• Daily cleaning with chlorhexidine-containing 
pads, shampoos, or solutions can be helpful; 
instruct owners not to scrub at the areas.• Gentamicin/steroid-containing ointments 
for the ears can be applied to localized lesions 
twice daily; most useful for lesions on the 
chin, as the pet cannot lick this area. Constant  
long-term use over months may cause alopecia 
and cutaneous atrophy: limit frequency and 
duration of application.
Systemic
• Antibiotics based on culture and sensitiv-
ity—when indicated (e.g., cephalexin, 
22–30  mg/kg PO q12h for 2–4 weeks).
• Oral corticosteroids: tapering dosages of 
prednisolone (initial 0.5  mg/kg/day) to 
reduce significant inflammation; not for 
continued use.
• Evaluate for and manage concurrent 
allergic/atopic skin disease.
• Topical steroids—may cause adrenal 
suppression and thinning of skin with 
frequent or constant use.
  FOLLOW-UP
• Continue antibiotics until lesions have 
healed.
• Repeat bacterial culture/sensitivity if lesions 
worsen.
• Discontinue topical corticosteroids when 
possible.
• Long-term topical treatment may be 
required.
• Chronic scarring may be prevented by early 
and aggressive therapy.
Allergic/atopic disease may cause and 
exacerbate this condition.
Miller WH, Griffin CE, Campbell KL. 
Muzzle folliculitis and furunculosis. In: 
Muller & Kirk’s Small Animal Dermatology, 
7th ed. St. Louis, MO: Elsevier, 2013, pp. 
201, 640.
Author  Melissa N.C. Eisenschenk
Resnick
acknowledge the prior contribution of Karen 
Helton Rhodes.

16 Blackwell’s Five-Minute Veterinary Consult  
AAcral Lick Dermatitis
  BASICS
OVERVIEW
• Compulsion to lick limb/s resulting in 
plaque formation.
• Skin/exocrine affected.
• Dogs.
• Most common in large breeds—Labrador 
retrievers, Doberman pinschers, Great Danes, 
Irish setters, golden retrievers, German 
shepherd dogs, boxers, and Weimaraners.
• Median age 4 yrs, range 1–12 yrs; no sex 
predilection.
SIGNS
• Excessive licking of affected area.
• Alopecic, eroded/ulcerated, thickened, and 
raised firm plaques with scabs and exudation, 
usually located on dorsal aspect of carpus, 
metacarpus, tarsus, or metatarsus.
• Single or multiple lesions.
• Anything causing local irritation or lesion 
may initiate lick–itch cycle.
• Associated diseases: staphylococcal 
furunculosis, hypersensitivity, endocrinopathy, 
demodicosis, dermatophytosis, foreign body 
reaction, neoplasia, underlying joint disease 
or arthritis, trauma, neuropathy, psychogenic, 
or sensory nerve dysfunction.
  DIAGNOSIS
• Bacterial furunculosis.
• Focal demodicosis.
• Focal dermatophytosis.
Usually normal.
Endocrinopathy—total T4/free T4/thyroid-
stimulating hormone (TSH); adrenocortico-
tropin hormone (ACTH) stimulation test or 
low-dose dexamethasone suppression test 
(LDDST).
IMAGING
Radiology (entire limb +/– neck/lumbar 
region)—neoplasia; local trauma; radiopaque 
foreign bodies; bony proliferation may be 
seen secondary to chronic irritation; evidence 
of underlying arthritis if over a joint.
• Dermatophyte PCR and/or culture—fungal 
• Epidermal cytology—bacterial infection.• Bacterial culture and sensitivity—tissue 
cultures may differ from surface culture.
• Food elimination diet—determine food 
allergy.
• Intradermal allergy testing—atopy.
• Biopsy—to rule out neoplasia, other 
infections.
• Behavioral history (additional behavioral 
signs typical).
• Neurologic and orthopedic evaluation.
Histopathology—epidermal hyperplasia, 
plasmacytic dermal inflammation, folliculitis, 
furunculosis, perihidradenitis, hidradenitis, 
epitrichial gland dilation/rupture, vertical 
streaking fibrosis.
  TREATMENT
• Rule in/out bacterial, fungal, ectoparasitic, 
endocrine causes and treat accordingly along 
with pruritus control.
• If infection resolves and pruritus and/or 
lesions persist, consider biopsy, allergy 
workup, neurologic/orthopedic exam, 
radiographs, behavioral modification.
• Physical restraints—to permit healing.
• Limited research to support effectiveness: 
radiation, acupuncture, CO2 laser, cryosurgery, 
standard surgery.
• Difficult to treat, especially if no underlying 
cause found; warn owner that patience and 
time are necessary.
Antibiotics
Based on bacterial culture/susceptibility. 
Administer until resolution of infection plus 
2 weeks.
Systemic
• Pruritus—antihistamines (2 weeks for 
response typically), e.g., hydroxyzine (2.2 mg/
kg PO q8h); chlorpheniramine (4–8 mg/dog 
PO q8–12h; maximum of 0.5 mg/kg q12h); 
amitriptyline (1–2 mg/kg PO q12h), also 
tricyclic antidepressant (TCA); corticoster-
oids, e.g., prednisolone 1 mg/kg PO q24h 
and taper based on response (or other steroid 
equivalent).
• Behavioral—selective serotonin reuptake 
inhibitors (SSRIs), e.g., fluoxetine (1 mg/kg 
PO q24h); TCAs, e.g., amitriptyline 
(1–2 mg/kg PO q12h, also antihistamine); 
doxepin (3–5 mg/kg PO q12h; maximum 
150 mg q12h); clomipramine (2–4 mg/kg 
PO q24h); dopamine antagonists, e.g., 
naltrexone (2.2 mg/kg PO q24h).• Combine/withdraw administration of these 
medications carefully.
Topical
Pruritus—flunixin meglumine and fluo-
cinolone in dimethyl sulfoxide (combined), 
topical capsaicin products; intralesional 
corticosteroids rarely helpful; wear gloves 
when applying; prevent licking of area for 
10–15 minutes.
• Doxepin—caution using with monoamine 
oxidase inhibitors, clonidine, anticonvulsants, 
oral anticoagulants, steroid hormones, anti  - 
histamines, or aspirin.
• Antihistamines—may cause sedation.
• Psychotropic medications should be 
combined and/or withdrawn carefully.
• Cardiotoxicity and hepatoxicity—rare cases 
in animals on TCAs. Routine monitoring 
recommended.
  FOLLOW-UP
• Monitor level of licking and chewing closely.
• T reat underlying disease to prevent 
recurrence.
• If no underlying disease detected, psycho-
genic causes possible (compulsive or self- 
mutilation disorder); prognosis is guarded.
Dogs <5 years old—strongly consider allergy.
Dermatophytosis (rare) and methicillin-resist-
ant Staphylococcus aureus  may have zoonotic 
implications.
• ACTH = adrenocorticotropin hormone.
• LDDST = low-dose dexamethasone 
suppression test.
• SSRI = selective serotonin reuptake 
inhibitor.
• TCA = tricyclic antidepressant.
• TSH = thyroid-stimulating hormone.
Shumaker AK. Diagnosis and treatment of 
canine acral lick dermatitis. Vet Clin North 
Am Small Anim Pract. 2019, 49:105–123.
Author  Heather D. Edginton
Resnick
Acknowledgment  The author acknowledges 
the prior contribution of Alexander H. 
Werner Resnick.

Canine and Feline, Seventh Edition  17
A Actinomycosis and Nocardia
  BASICS
OVERVIEW
• Opportunistic bacterial infections caused 
by branching Gram-positive bacteria that 
cause clinically similar suppurative-to-
granulomatous inflammation:
◦ Actinomyces  spp. (anaerobic-to-
microaerophilic, normal flora of mucous 
membranes, gastrointestinal and urogenital 
tracts).
◦ Nocardia  spp. (aerobic soil saprophytes).
• Organ systems affected may include:
◦ Skin and subcutaneous.
◦ Respiratory.
◦ Cardiovascular.
◦ Musculoskeletal.
◦ Nervous.
◦ Disseminated ( Nocardia ).
• Dogs and cats (uncommon).
• Dogs with outdoor access ( Actinomyces ); 
young dogs ( Nocardia ); male cats (both).
SIGNS
• Depends on whether infection is localized 
or disseminated ( Nocardia ) and on organ 
systems involved.
• Cutaneous and subcutaneous swellings 
(cervicofacial— Actinomyces ), abscesses, or 
nonhealing wounds with draining tracts; 
localized draining cutaneous lesions are 
common in cats.
• Poor body condition, pain, fever, weight loss.
• Exudative pleural or peritoneal effusions.
• Cough, dyspnea, decreased ventral lung 
sounds (empyema).
• Lameness due to osteomyelitis.
• Motor and sensory deficits.
• Retroperitonitis ( Actinomyces )—lumbar 
pain, rear limb paresis or paralysis.
Scratches and bite wounds, traumatic 
inoculation, foreign body migration (e.g., 
grass awn), immunosuppression ( Nocardia ).
  DIAGNOSIS
• Actinomyces  and Nocardia  appear similar 
and are not reliably distinguished by Gram 
staining, cytology, or clinical signs. 
Actinomyces  is usually accompanied by 
multiple other coinfective bacteria.
• Other causes of similar clinical signs must 
be considered, including other bacterial or 
fungal infections, neoplasia, and other 
diseases that cause effusions.CBC/BIOCHEMISTRY/URINALYSIS
• Nonregenerative anemia.
• Leukocytosis with a left shift and mono- 
cytosis.
• Hyperglobulinemia.
• Ionized hypercalcemia (nocardiosis).
N/A
IMAGING
• Dependent on systems affected.
• Thoracic radiographs—alveolar and 
interstitial lung pattern with possible alveolar 
disease, pleural effusion (pyothorax), peri  - 
cardial effusion, subcutaneous masses.
• Abdominal radiographs—peritoneal 
effusion, abdominal mass effect.
• Radiographs of infected bone—periosteal 
new bone, reactive osteosclerosis, osteolysis.
• Gram staining, cytology, and acid-fast 
staining are helpful, but do not preclude the 
need for culture; acid-fast stain— Actinomyces  
negative, Nocardia  variable; sulfur granules 
suggest Actinomyces .
• Exudates or osteolytic bone fragments 
submitted in aerobic and anaerobic 
specimen containers for culture can provide 
a definitive diagnosis (see Anaerobic 
Infections).
• Nocardia may require speciation if not 
responding to empiric therapy.
Histopathologic examination— 
pyogranulomatous or granulomatous cellulitis 
with colonies of filamentous bacteria; special 
stains may enhance visualization. Sulfur 
granules are a useful diagnostic tool, but can 
be difficult to find.
  TREATMENT
• Prolonged antimicrobial therapy is 
required.
• Surgical debridement or excision of infected 
tissue (e.g., lung lobe, body wall mass) may 
improve outcome.
• Exudative fluid (thorax, abdomen, subcut -
aneous tissue) should be drained and the 
infected cavity lavaged.
• A thoracostomy tube with intermittent or 
continuous drainage is usually needed for cats 
with pyothorax; dogs may benefit from 
surgical exploration of thorax prior to 
thoracostomy tube placement to attempt 
foreign body removal.  MEDICATIONS
• Important to distinguish between 
Actinomyces  and Nocardia  for appropriate 
antimicrobial selection.
• Antibiotics—protracted course of therapy 
(weeks to months) usually required; continue 
for several weeks after resolution of all signs.
• Actinomycosis—penicillins considered drug 
of choice; amoxicillin: 20–40 mg/kg PO q8h.
• Nocardiosis—potentiated sulfonamides at 
15–30 mg/kg PO q12h are usually first choice.
• Dogs can develop toxic or hypersensitivity 
adverse reactions to sulfonamides.
• Metronidazole and aminoglycosides are 
ineffective against Actinomyces  spp.
  FOLLOW-UP
Monitor closely for recurrence after therapy 
discontinued.
Avoid areas with grass awns; prevent bites and 
scratches.
Difficult to fully clear infection.
• Redevelopment of infection after discontinu-  
ation of antibiotics is possible.
• Actinomyces —up to 90% cure reported in 
dogs after appropriate therapy.
• Nocardia —up to 50% mortality reported.
Young outdoor dogs.
No reports of humans being infected by 
either organism through direct contact. Bite 
and scratch wounds can cause human disease.
SEE ALSO
Anaerobic Infections.
Sykes JE. Actinomycosis and nocardiosis. In: 
Greene CE, ed., Infectious Diseases of the 
Dog and Cat, 4th ed. St. Louis, MO: 
Saunders Elsevier, 2011, pp. 484–495.
Author  Sharon Fooshee Grace

18 Blackwell’s Five-Minute Veterinary Consult  
AAcute Abdomen
  BASICS
An emergency condition characterized by 
historical and physical examination findings 
of a tense, painful abdomen. May represent a 
life-threatening condition.
• An affected patient has pain associated with 
either distention of an organ, inflammation, 
traction on the mesentery or peritoneum, or 
ischemia.
• Abdominal viscera are sparsely innervated, 
and diffuse involvement is often necessary to 
elicit pain; nerve endings also exist in the 
submucosa-muscularis of the intestinal wall.
• Inflammation produces abdominal pain by 
releasing vasoactive substances that directly 
stimulate nerve endings.
• Behavioral—trembling, inappetence, vocalizing, 
lethargy, and abnormal postural changes such as 
the praying position to achieve comfort.
• Cardiovascular—ischemia, severe inflamm -
ation, systemic inflammatory response 
syndrome and sepsis may lead to shock. 
Tachycardia or other arrhythmia may affect 
capillary refill time and mucous membrane 
color. Pain may cause arrhythmias.
• Gastrointestinal (GI)—vomiting, diarrhea, 
inappetence, generalized functional ileus; 
pancreatic inflammation, necrosis, and 
abscesses may lead to cranial abdominal pain, 
vomiting, and ileus.
• Hepatobiliary—jaundice associated with 
cholestasis from biliary obstruction (including 
pancreatitis) or bile peritonitis. Hyperbili -
rubinemia may occur secondary to sepsis.
• Renal/urologic—azotemia due to prerenal 
(dehydration, hypovolemia, and shock), renal 
(acute pyelonephritis and acute kidney injury), 
and postrenal causes (ureteral obstruction, 
urethral obstruction, and uroperitoneum 
from bladder rupture).
• Respiratory—increased respiratory rate due 
to pain or metabolic/acid-base disturbances.
Species
• Dogs and cats.
• Dogs more commonly; often challenging to 
identify abdominal pain in feline patients.
• Male Dalmatians have a higher risk of 
urethral obstruction because of the high 
incidence of urate urolithiasis.
• German shepherds with pancreatic atrophy 
have a higher risk of mesenteric volvulus.
AnyPredominant Sex
Male cats and dogs are at higher risk for 
urethral obstruction.
SIGNS
Clinical signs vary greatly, depending on type 
and severity of underlying disease.
• T rembling, reluctance to move, inappetence, 
vomiting, diarrhea, vocalizing, and abnormal 
postures (tucked up or praying position).
• Question owner carefully to ascertain what 
system is affected; for example, melena with a 
history of nonsteroidal anti-inflammatory 
drug (NSAID) treatment may suggest GI 
mucosal ulceration.
• Abdominal pain, splinting of abdominal 
musculature, gas- or fluid-filled abdominal 
organs, abdominal mass, ascites, pyrexia or 
hypothermia, tachycardia, and tachypnea.
• Pain may be localizable to cranial, middle, 
or caudal abdomen.
• Perform rectal examination to evaluate 
colon, pelvic bones, urethra, and prostate, as 
well as for presence of melena.
• Rule out extra-abdominal causes of pain by 
careful palpation of kidneys and thoracolumbar 
vertebrae.
• Pain associated with intervertebral disc 
disease often causes referred abdominal 
guarding and may be mistaken for true 
abdominal pain. Renal pain can be associated 
with pyelonephritis.
CAUSES
GI
• Stomach—gastritis, ulceration, perforation, 
foreign body, gastric dilatation-volvulus.
• Intestine—obstruction (foreign body, 
intussusception, mass, etc.), enteritis, ulcer- 
ation, perforation.
• Rupture after obstruction, ulceration, or 
blunt or penetrating trauma, or due to tumor 
growth.
• Vascular compromise from infarction, 
mesenteric volvulus, or torsion.
Pancreas
• Inflammation, abscess, ischemia.
• Mass or inflammation obstructing common 
bile duct may cause jaundice.
Hepatic and Biliary System
• Acute hepatitis—rapid distention of the 
liver and its capsule can cause pain.
• Biliary obstruction, rupture, or necrosis 
may lead to bile leakage and peritonitis.
• Gallbladder mucocele.
• Hepatic abscess.
Spleen
Torsion, mass, thrombus, abscess.Urinary Tract
• Distention is main cause of pain in urinary 
tract.
• Obstruction due to tumors of trigone area 
of bladder or urethra, urinary calculi, or 
granulomatous urethritis.
• T raumatic rupture of ureters or bladder.
• Urethral tear associated with pelvic fractures 
from acute trauma.
• Uroabdomen leads to chemical peritonitis.
• Acute pyelonephritis, acute kidney injury, 
nephroliths, and ureteroliths are uncommon 
causes of acute abdomen.
Genital Tract
• Prostatitis and prostatic abscess, pyometra; 
a ruptured pyometra or prostatic abscess can 
cause endotoxemia, sepsis, and cardiovascular 
collapse.
• Uncommon—rupture of gravid uterus after 
blunt abdominal trauma, uterine torsion, 
ovarian tumor or torsion, and intra-
abdominal testicular torsion (cryptorchid).
Abdominal Wall/Diaphragm
• Umbilical, inguinal, scrotal, abdominal, 
or peritoneal hernia with strangulated  
viscera.
• Organ displacement or entrapment in 
hernia will lead to abdominal pain if vascular 
supply of organ(s) involved becomes impaired 
or ischemic.
• Exposure to NSAIDs or corticosteroid treat-  
ment (increased risk when used concurrently)—
gastric, duodenal, or colonic ulcers.
• Garbage or fatty food ingestion—pancreatitis.
• Foreign body ingestion—intestinal 
obstruction.
• Abdominal trauma—hollow viscus rupture.
• Hernia—intestinal obstruction/strangulation.
  DIAGNOSIS
• Renal-associated pain, retroperitoneal pain, 
spinal or paraspinal pain, and disorders 
causing diffuse muscle pain may mimic 
abdominal pain; careful history and physical 
examination are essential in pursuing the 
appropriate problem.
• Parvoviral enteritis can present similarly to 
intestinal obstructive disease; fecal parvoviral 
antigen assay and CBC (leukopenia) are 
helpful differentiating diagnostic tests.
• Inflammation or infection may be 
associated with leukocytosis or leukopenia.
• Active inflammation may be characterized 
by a neutrophilic left shift.
• Anemia may be seen with blood loss 
associated with GI ulceration.

Canine and Feline, Seventh Edition  19
A
• Azotemia is associated with prerenal, renal, 
and postrenal causes.
• Electrolyte abnormalities can help to 
evaluate GI disease (i.e., hypochloremic 
metabolic alkalosis with gastric outflow 
obstruction) and renal disease (i.e., hyper -
kalemia with acute kidney injury or postrenal 
obstruction).
• Hyperbilirubinemia and increased hepatic 
enzyme activity help localize a problem to 
liver or biliary system.
• Urine specific gravity (before fluid therapy) 
is needed to help differentiate prerenal, renal, 
and postrenal azotemia.
• Urine sediment may be helpful in acute 
kidney injury, ethylene glycol intoxication, 
and pyelonephritis.
• Venous blood gas analysis including lactate 
concentration may indicate acid-base 
abnormalities, and increased lactate may be 
associated with hypoperfusion.
• Canine and feline pancreatic lipase immuno -
reactivity can be useful in evaluating 
pancreatitis.
IMAGING
Abdominal Radiography
• May see abdominal mass or changes in 
shape or shifting of abdominal organs.
• Loss of abdominal detail suggests 
abdominal fluid accumulation.
• Free abdominal gas suggests ruptured GI 
viscus or infection with gas-producing bacteria 
and is indication for emergency surgery.
• Use caution when interpreting radiographs 
following abdominocentesis with an open 
needle. Free gas may be introduced with this 
technique.
• Use caution when evaluating postoperative 
radiographs; free gas is a normal postoperative 
finding.
• Diffuse GI distension is a consistent finding 
with peritonitis.
• Foreign bodies may be radiopaque.
• Upper GI barium contrast radiographs are 
useful in evaluating the GI tract, particularly 
for determination of GI obstruction.
• Loss of contrast or radiographic detail in 
the area of the pancreas can be observed with 
pancreatic inflammation.
Abdominal Ultrasound
• A sensitive diagnostic tool for detection of 
GI obstruction, pancreatitis, abdominal 
masses, abdominal fluid, abscesses, cysts, 
lymphadenopathy, and biliary or urinary 
calculi.
• Focused Assessment with Sonography in 
T rauma (FAST) may be used for rapid 
assessment.
Abdominal CT
May provide superior information to 
ultrasound in large patients; useful when 
surgeon requires additional information.DIAGNOSTIC PROCEDURES
Abdominocentesis/Abdominal Fluid 
Analysis
• Perform abdominocentesis on all patients 
presenting with acute abdomen. Four-
quadrant approach may improve yield. Fluid 
can often be obtained for diagnostic evalu -
ation, even when only a small amount of free 
abdominal fluid exists, well before detectable 
radiographically. Ultrasound is much more 
sensitive than radiography for detection of 
fluid and can be used to direct 
abdominocentesis. Blind abdominocentesis 
can be performed safely without ultrasound 
guidance. Abdominal fluid analysis with 
elevated white blood cell (WBC) count, 
degenerate neutrophils, and intracellular 
bacteria is consistent with septic peritonitis 
and is an indication for immediate surgery.
• Diagnostic peritoneal lavage can be performed 
by introducing sterile saline (10–20 mL/kg) and 
performing abdominocentesis, with or without 
ultrasound guidance.
• Measurement of glucose concentration in 
abdominal effusion in comparison with 
peripheral blood may aid in diagnosis of 
septic abdomen. A blood-to-abdominal fluid 
glucose difference of >20 mg/dL is consistent 
with septic effusion.
• Pancreatitis patients may have abdominal 
effusion characterized as nonseptic (sterile) 
peritonitis.
• Creatinine concentration higher in 
abdominal fluid than in serum indicates 
urinary tract leakage.
• Similarly, higher bilirubin concentration in 
abdominal fluid than in serum indicates bile 
Sedation and Abdominal Palpation
Because of abdominal splinting associated 
with pain, thorough abdominal palpation is 
often not possible without sedation; this is 
particularly useful for detecting intestinal 
foreign bodies that do not appear on survey 
radiographs.
Exploratory Laparotomy
Surgery may be useful diagnostically (as well 
as therapeutically) when ultrasonography (or 
other advanced imaging) is not available, or 
when no definitive cause of acute abdomen 
has been established with appropriate 
diagnostics.
Varies with underlying disease.
  TREATMENT
• Inpatient management with supportive care 
until decision about whether problem to be 
treated medically or surgically. Early inter- vention with surgery is important when 
indicated.
• Aggressive therapy and prompt identification 
of underlying cause are very important.
• Many causes of acute abdominal pain 
require emergency surgical intervention.
• Keep patient NPO if vomiting, until a 
definitive cause is determined and addressed.
• Intravenous fluid therapy usually required 
because of large fluid loss associated with 
acute abdomen; goal is to restore normal 
circulating blood volume.
• If shock exists, supplement initially with 
isotonic crystalloid fluids (up to 90 mL/kg, 
dogs; 70 mL/kg, cats) to restore volume; 
hypertonic fluids or colloids may also be 
beneficial if refractory to isotonic crystalloids 
or hypoproteinemic.
• Evaluate hydration and electrolytes (with 
appropriate treatment adjustments) frequently 
after commencement of treatment.
ACTIVITY
N/A
DIET
Early nutritional support is important. 
Nutritional support can be enteral (oral, 
nasoesophageal, esophageal tube, gastrostomy 
tube, enterostomy tube) or parenteral.
Acute abdomen may represent a life-threatening 
condition. Prompt diagnosis and appropriate 
treatment essential to a favorable outcome.
• Many different causes of acute abdomen 
exist; make definitive diagnosis whenever 
possible prior to surgical intervention.
• Definitive diagnosis prior to surgery can 
prevent both potentially unnecessary and 
expensive surgical procedures and associated 
morbidity and mortality.
• Also allows surgeon to prepare for task and 
educate owner on prognosis and financial 
investment.
Analgesics
• Pain medication may be indicated for 
control of abdominal discomfort.
• Opioids are good choices.
◦ Fentanyl—2–5  μg/kg as initial IV bolus, 
2–10  μg/kg/h as CRI.
◦ Hydromorphone—0.05–0.2 mg/kg SC/
IM/IV q4–6h.
◦ Morphine—0.5–2 mg/kg SC/IM, q4–6h.
◦ Buprenorphine—0.01–0.02 mg/kg SC/
◦ Methadone—0.1–0.4 mg/kg SC/IM/IV 
q6h.(continued)  Acute Abdomen

20 Blackwell’s Five-Minute Veterinary Consult  
A
Histamine H2 Antagonists
• Reduce gastric acid production.
• Famotidine 0.5–1 mg/kg IV/SC/IM q12h.
• Ranitidine 2 mg/kg IV q12h.
Proton Pump Inhibitor
Pantoprazole 0.5 mg/kg IV q12h or 0.05– 
0.1 mg/kg/hr as CRI.
Protectants
Sucralfate 0.25–1 g PO q8h.
Antiemetics
• Metoclopramide 0.2–0.4 mg/kg IV q6–8h 
(or 24-hour CRI at 1–2 mg/kg/24h).
• Maropitant: dogs 2–4 months of age, 1 mg/
kg SC q 24h; dogs >4 months of age and cats, 
1 mg/kg SC/IV q24h.
• Ondansetron 0.2–0.5 mg/kg IV slowly 
q6–12h.
• Antibiotics may be indicated if signs of 
infection are seen or hemorrhagic diarrhea 
is present.
• Broad-spectrum coverage pending culture 
results.
• Obtain cultures prior to treatment if 
possible, but do not delay intervention if 
• Do not use metoclopramide if GI 
obstruction is suspected.
• Do not use barium if GI perforation is 
suspected; use iodinated contrast agent instead.
• Gentamicin and NSAIDs can be 
nephrotoxic and should be avoided in hypovolemic patients and those with renal 
impairment.
• NSAIDs may also cause GI 
complications.
N/A
ALTERNATIVE DRUGS
N/A
  FOLLOW-UP
Patients usually require intensive medical care 
and frequent evaluation of vital signs and 
laboratory parameters.
Avoidance of indiscriminate eating may 
prevent GI foreign body obstruction and 
decrease incidence of pancreatitis.
Varies with underlying cause.
EXPECTED COURSE AND  
PROGNOSIS
Varies with underlying cause; guarded until 
this is determined.
Younger animals have higher incidence of 
trauma-related problems, intussusceptions, and acquired diet- and infection-related 
diseases; older animals have higher incidence 
of malignancies.
SYNONYMS
Colic
SEE ALSO
• Gastric Dilation and Volvulus Syndrome.
• Gastroduodenal Ulceration/Erosion.
• Gastrointestinal Obstruction.
• Intussusception.
• Pancreatitis—Cats.
• Pancreatitis—Dogs.
• Prostatitis and Prostatic Abscess.
• Pyelonephritis.
• Urinary T ract Obstruction.
• FAST = Focused Assessment with 
Sonography in T rauma.
drug.
• WBC = white blood cell.
Beal MW. Approach to the acute abdomen. 
Vet Clin North Am Small Anim Pract 2005, 
35:375–396.
Heeren V, Edwards L, Mazzaferro EM. Acute 
abdomen: diagnosis. Compend Contin 
Educ Pract Vet 2004, 26:350–363.
abdomen: treatment. Compend Contin 
Educ Pract Vet 2004, 26:3566–3673.
Author  Steven L. Marks
Consulting Editor  Mark P . RondeauAcute Abdomen  (continued)

Canine and Feline, Seventh Edition  21
A Acute Diarrhea
  BASICS
Nonepisodic diarrhea of fewer than 7 days’ 
duration.
Excess water and/or solid content of feces is 
caused by five main mechanisms:
• Osmotic—from maldigestion, ingestion of 
poorly absorbable compounds, toxins. 
• Decreased absorption—mucosal damage 
causing loss of absorptive cells from infection, 
inflammation, or toxins. • Increased secretion 
(secretory)—mediated by toxins, inflamma-
tion, parasympathetic stimulation. 
• Increased permeability/exudative—severe 
mucosal, lacteal, and vessel damage, due to 
inflammation, ulceration, or direct damage. 
• Dysmotility—increased or decreased 
motility alters digestion, absorption, 
secretion, and therefore water regulation.
• Cardiovascular—fluid losses can be significant, 
with progressive dehydration to hypovolemia. 
• Gastrointestinal (GI)—colitis can develop 
secondary to orad causes of diarrhea. 
• Immune—with enterocyte loss, the mucosal 
barrier can be compromised, leading to trans-  
location of GI bacteria and sepsis. • Metabolic—
electrolyte losses, especially bicarbonate and 
potassium. Hypokalemia is common with 
concurrent hyporexia. • Vascular—albumin and 
globulin losses via increased permeability can be 
significant and lead to hypoalbuminemia, 
decreased vascular oncotic pressure, and edema 
or cavitary effusion.
GENETICS
N/A
Increased incidence due to dietary indiscretion 
or infectious etiologies in young patients.
Some infectious etiologies have specific 
geographic distributions.
• Species—dog and cat. • Breed predilec-
tions—none. • Mean age and range—com-
mon in puppies and kittens due to dietary 
indiscretion and infectious etiologies. 
• Predominant sex—N/A.
SIGNS
• Acute diarrhea common, and usually self-  
limiting. Most animals stable, and require 
minimal diagnostics/treatment. • In patients 
that are unstable, with cardiovascular or 
metabolic compromise, more aggressive 
diagnostic and treatment approach is warranted.Historical Findings
• Dietary history, dietary indiscretion, 
medication/toxin history, and general 
husbandry should be investigated. ◦ Special 
care should be taken to identify potentially 
contagious causes of diarrhea, and isolate 
these patients early. ◦ Patients that should be 
isolated for further diagnostics include 
unvaccinated, raw diet consumption, housing 
with many other cats/dogs, or multiple cats/
dogs from same household affected. 
• Varying activity levels can be seen, from 
normal to lethargic. • Character of diarrhea 
can help localize etiology: ◦ Small intestinal 
diarrhea characteristics: large volume, normal 
frequency, concurrent weight loss and/or 
vomiting. ◦ Melena, if present, points to 
gastric or upper small intestinal bleed. 
◦ Steatorrhea, if present, points to maldigestive 
disorder like exocrine pancreatic insufficiency 
(EPI). ◦ Large intestinal diarrhea 
characteristics—small volume, increased 
frequency, tenesmus, mucus, hematochezia.
• Patients can vary from stable to unstable. 
• Common findings—dehydration, 
hypovolemia, abdominal pain, nausea, 
fluid–gas interface on intestinal palpation, 
increased borborygmi. • Rectal examination 
may reveal melena, hematochezia, steatorrhea.
CAUSES
• Extra-GI causes: ◦ Common—hepatobiliary 
disease, pancreatitis, neoplasia (non-GI). 
◦ Uncommon—endocrine (hypoadrenocorti -
cism, hyperthyroidism), peritonitis, sepsis. 
• Intra-GI causes: ◦ Infectious—bacterial: 
Campylobacter  spp., E. coli , Salmonella  spp., 
Clostridial enterotoxins; parasitic: many species 
of ascarids, cestodes, hookworms, whipworms; 
protozoal: giardiasis, tritrichomoniasis, 
coccidiosis; viral: parvovirus, canine distemper 
virus, corona virus; rickettsial: salmon 
poisoning ( Neorickettsia ); fungal: histoplasmo -
sis, mycotoxins. ◦ Inflammatory (most 
common cause)—acute enteritis/enterocolitis 
due to dietary indiscretion or sudden diet 
change, acute hemorrhagic diarrhea syndrome. 
◦ Medications/toxins—antibiotics, chemo -
therapeutic agents, methimazole, nonsteroidal 
anti-inflammatory drugs (NSAIDS), toxins 
(corrosive, heavy metals). ◦ Motility—obstruc -
tive or nonobstructive foreign bodies, intussus  - 
ception, mesenteric torsion. ◦ Neoplasia—  
primary neoplasia including adenocarcinoma, 
lymphoma (small cell and large cell) leiomy -
oma/leiomyosarcoma, mast cell tumor (cats), 
metastatic.
• Dietary—abrupt diet change or dietary 
indiscretion. • Medications—many medica-
tions can cause acute diarrhea (see Causes). 
• Infectious—geographic distribution effect.  DIAGNOSIS
Unlikely to be confused with other conditions; 
however, rarely intestinal bleeding or expulsion 
of liquid in constipated patient can mimic 
acute diarrhea.
• Extra-GI etiologies—may reflect etiology: 
◦ Increased hepatic enzyme activity in 
hepatobiliary diseases. ◦ Increased hepatic 
enzyme activity, hypoalbuminemia, 
inflammatory leukogram in pancreatitis. 
◦ Hypoalbuminemia, decreased Na : K ratio 
in hypoadrenocorticism. • Intra-GI causes 
of diarrhea—often normal. • Parvoviral 
enteritis causes significant neutropenia.  
• As result of diarrhea, following may be 
present: ◦ Hemoconcentration.  ◦ Prerenal 
azotemia. ◦ Hypokalemia. ◦ Hypoalbuminemia, 
hypocholesterolemia. ◦ Hypoglycemia—toy 
breed puppies with GI signs predisposed.
• Extra-GI interrogation: ◦ Baseline cortisol 
or adrenocorticotropic hormone (ACTH) 
stimulation test in dogs. ◦ T4 in cats. 
◦ Quantitative pancreatic lipase immunore-
activity. ◦ T rypsin-like immunoreactivity if 
EPI suspected. • Intra-GI interrogation: 
◦ Parvovirus ELISA should be immediately 
performed in any suspect so isolation 
protocols may be initiated as soon as possible. 
◦ Fecal flotation, fecal direct smear cytology, 
Giardia  ELISA. ◦ Diarrhea PCR panel may 
be useful for specific pathogens (i.e., Salmonella ), 
but note there is controversy about some 
bacteria on this panel causing clinical signs.
IMAGING
• Survey abdominal radiographs interrogate 
mainly extra-GI causes of diarrhea. • Acute 
enteritis/enterocolitis—mild gas and/or fluid 
dilation of stomach/intestine. • Pancreatitis—
widened gastroduodenal angle, focal decreased 
serosal detail at proximal duodenal flexure.
Abdominal Ultrasonography
• Abdominal ultrasonography may be useful 
in interrogation of intra- and extra-GI causes 
of diarrhea, such as pancreatitis. • Emergency 
cage-side focused ultrasonographic examina-
tion of abdomen is indicated in patients with 
acute abdominal pain, to evaluate for etiologies 
that are surgical emergencies, such as septic or 
bile peritonitis. • If peritoneal effusion is 
seen, abdominocentesis and immediate 
in-house cytology are indicated (+/– culture).
Endoscopy rarely indicated in acute diarrhea, 
except for patients with melena where gastro  - 
duodenal ulceration is suspected.

22 Blackwell’s Five-Minute Veterinary Consult  
A
Dependent on underlying etiology.
  TREATMENT
• Stable patients, mild diarrhea—outpatient 
medical care. Careful assessment of young 
patients should be made, as they can become 
unstable with mild signs. • Unstable patients, 
hypovolemic or acute abdominal pain—inpa-
tient medical care.
• Isolation protocols should be instituted 
immediately for any patient that may have a 
contagious etiology of diarrhea, i.e., patients 
that are unvaccinated, fed raw diets, come 
from housing situations with many other 
animals, or if multiple animals in same 
household are exhibiting same clinical signs. 
• Fluid therapy as mandated by hydration/
perfusion status and ongoing losses. • Most 
hyporexic patients with dehydration/hypo  - 
volemia need isotonic crystalloids to replenish 
losses and provide maintenance. • Potassium 
supplementation may be needed.
ACTIVITY
Activity restriction only required in post -
operative care of surgical patients.
DIET
Feeding bland, highly digestible diet is 
indicated for 3–5 days, then gradual 
reintroduction of patient’s routine diet.
Client education on dietary indiscretion, 
gradual diet changes, routine deworming, and 
vaccination may be appropriate.
Surgery rarely may be indicated to treat 
etiology, such as mechanical obstruction.
• In acute diarrhea caused by stress or 
antibiotics, veterinary-grade probiotics may 
be useful. • Antibiotics not indicated in acute 
diarrhea patients, and should be avoided in 
accordance with antibiotic stewardship, unless 
specifically indicated with known bacterial 
etiology, or in cases where bacterial transloca-
tion and sepsis are of concern (e.g., parvoviral 
enteritis with neutropenia). Gastric antacids 
not indicated unless concurrent vomiting 
and/or regurgitation. • Anti-diarrheal 
medications like loperamide not indicated in acute diarrhea, as usually self-limiting; if 
diarrhea persists beyond 5–7 days, further 
etiologic investigation and appropriate 
treatment are warranted. • Anthelmintics 
(e.g., fenbendazole 50 mg/kg PO q24h for 5 
days) are recommended for empiric treatment 
of parasitic enteritis. • Antiprotozoal or 
coccidiostatic medication should be used if 
fecal analysis warrants.
• Prokinetic medications should not be given 
to patients with diarrhea. • Anti-diarrheal 
medications like loperamide should not be 
given to breeds with possible ABCB-1/
MDR-1 mutation.
• For puppies and kittens, see manufacturer’s 
instructions regarding age and safety labeling. 
• Many drugs such as antibiotics and anti- 
diarrheal medications can perpetuate diarrhea. 
• Metronidazole can cause neurologic toxic 
effects with high dose and/or chronic use.
N/A
N/A
  FOLLOW-UP
• Continuation of diarrhea for 3–5 days is to 
be expected, but should be continual improve -
ment in signs. • If diarrhea not improving, or 
getting more severe, further diagnostics are 
warranted. • If diarrhea persists beyond 7 
days or recurs despite appropriate therapy, 
consider chronic diarrhea etiologies.
Avoid rapid diet changes and dietary 
indiscretion, and institute prophylactic 
deworming and vaccinations.
• Dehydration and hypovolemia. 
• Hypoalbuminemia and subsequent cavitary 
effusion.
• Mild acute diarrhea usually self-limiting. 
• Other prognoses etiology dependent.
• Acute vomiting. • Hyporexia.AGE-RELATED FACTORS
Younger patients more likely to have 
infectious etiologies.
Parasitic, protozoal, and bacterial etiologies 
(e.g., Ancylostoma , Campylobacter , Giardia , 
Salmonella ).
Varies with treatment.
SYNONYMS
N/A
SEE ALSO
• Acute Vomiting. • Diarrhea, Chronic—
Cats. • Diarrhea, Chronic—Dogs. 
• Gastroenteritis, Acute Hemorrhagic 
Diarrhea Syndrome. • Pancreatitis—Cats. 
• ACTH = adrenocorticotropic hormone. 
• EPI = exocrine pancreatic insufficiency. 
• GI = gastrointestinal. • NSAID = non-
steroidal anti-inflammatory.
• https://www.avma.org/practicemanagement/
clientmaterials/pages/default.aspx • https://
veterinarypartner.vin.com
Hall J. Physiology of gastrointestinal 
disorders. In: Hall J, ed., Guyton and Hall’s 
Textbook of Medical Physiology, 13th ed. 
Philadelphia, PA: Elsevier, 2016, 843–852.
Marks SL, Kook PH, Papich MG, et al. 
ACVIM consensus statement: Support for 
rational administration of gastrointestinal 
protectants to dogs and cats. J Vet Intern 
Med 2018, 32:1823–1840.
Marks SL, Rankin SC, Byrne BA, Weese JS. 
Enteropathogenic bacteria in dogs and cats: 
diagnosis, epidemiology, treatment, and 
control. J Vet Intern Med 2011, 25: 
1195–1208.
Weese JS, Giguère S, Guardabassi L, et al. 
ACVIM consensus statement on therapeu-
tic antimicrobial use in animals and 
antimicrobial resistance. J Vet Intern Med 
2015, 29:487–498.
Willard MD. Diarrhea. In: Ettinger SJ, ed., 
Textbook of Veterinary Internal Medicine, 
8th ed. St. Louis, MO: Elsevier, 2017, pp. 
164–166.
Author  Talia Guttin
Consulting Editor  Mark P . Rondeau
Acknowledgment  The author and editor 
acknowledge the prior contribution of 
Erin Portillo.
available onlineAcute Diarrhea  (continued)

Canine and Feline, Seventh Edition  23
A Acute Kidney Injury
  BASICS
• Acute kidney injury (AKI) represents a 
continuum of renal injury, from mild, 
clinically inapparent, nephron loss to severe 
acute renal failure.
• AKI is likely underrecognized. Any increase 
in serum creatinine >0.3 mg/dL from 
hydrated baseline is considered an AKI.
• The spectrum of injury is highly variable 
and may range from mild subclinical to 
severe damage, requiring renal replacement 
therapy.
• Patients with AKI have the potential for 
recovery of renal function.
• AKI may be categorized as prerenal, 
intrinsic renal, or postrenal based on under­
lying etiology. Pre ­ and postrenal causes may 
progress to intrinsic renal damage.
• Patients with preexisting chronic kidney 
disease (CKD) are very predisposed to develop­
ment of clinical AKI due to decreased renal 
reserve. Special care must be taken in patients 
with existing CKD to minimize predisposing 
factors: volume depletion, nephrotoxic 
medications, etc.
• Renal/urologic.
• Uremia may affect all body systems.
• Prevalence is lower than for CKD.
• Prevalence may increase in environments 
that support Leptospira .
• Ureteral obstruction is most common cause 
of severe acute uremia in cats.
Species
None
• 6–8 years peak prevalence.
• Older animals at greater risk due to 
decreased renal reserve (AKI on CKD).
SIGNS
Sudden onset of anorexia, listlessness, 
depression, vomiting or diarrhea (± blood), 
halitosis, ataxia, seizures, known toxin or drug 
exposure, recent medical or surgical 
procedure.
Normal body condition and hair coat, 
depression, dehydration (or iatrogenic 
overhydration), scleral injection, oral 
ulceration, necrosis of tongue, uremic breath, 
hypothermia, fever, tachypnea, bradycardia, 
nonpalpable urinary bladder, and asymmetric, 
enlarged, painful, or firm kidneys.CAUSES
Hemodynamic/Hypoperfusion
Shock, trauma, thromboembolism 
(e.g., disseminated intravascular coagulation 
[DIC]), vasculitis, transfusion reaction), 
heatstroke, excessive vasoconstriction (e.g., 
administration of nonsteroidal anti ­inflammatory 
drugs [NSAIDs]), adrenal insufficiency, 
excessive vasodilation (e.g., angiotensin ­ 
converting enzyme inhibitors [ACEIs] or 
antihypertensive drugs), prolonged anesthesia, 
significant hypertension, heart failure.
Nephrotoxic
Grape or raisin ingestion (dogs), lily ingestion 
(cats), ethylene glycol, aminoglycoside, 
amphotericin B, chemotherapeutic agents, 
NSAIDs, radiographic contrast agents, heavy 
metals, insect or snake venom, heme pigment, 
and many others. Patients with ethylene 
glycol toxicity may be exposed from other 
sources than antifreeze, such as some paints, 
freezer packs, catering heat sources, etc.
Intrinsic and Systemic Disease
Leptospirosis, immune ­mediated 
glomerulonephritis, pancreatitis, septicemia, 
DIC, hepatic failure, heat stroke, transfusion 
reaction, bacterial endocarditis, pyelonephritis, 
lymphoma, and ureteral obstruction.
• Endogenous—preexisting CKD, 
pancreatitis, dehydration, sepsis, hypovolemia, 
hypotension, advanced age, concurrent disease.
• Exogenous—drugs, prolonged anesthesia, 
trauma, multiple organ disease, high 
environmental temperature.
  DIAGNOSIS
• Prerenal azotemia—oliguria correctable 
with fluid repletion. Typically hypersthenuric, 
but consider ability to concentrate urine: 
preexisting kidney disease, endocrine 
disorders, medications, and diet may all affect 
concentrating ability.
• Postrenal azotemia—anuria, dysuria, 
stranguria, painful or asymmetric kidneys, 
ureteral/urethral obstruction, enlarged 
prostate, urethral tear, uroperitoneum.
• CKD—polyuria, polydipsia, history of 
chronic illness, loss of body condition, anemia.
• Hypoadrenocorticism—hyponatremia, 
hyperkalemia, low serum cortisol.
• Pancreatitis—cranial abdominal pain, 
hyperbilirubinemia, increase in liver enzyme 
activity.
• Variable packed cell volume (PCV), 
leukocytosis, or lymphopenia.
• Variable increases in blood urea nitrogen 
(BUN), creatinine, phosphorus, potassium, 
and glucose; and variably low bicarbonate and 
calcium.• Urine specific gravity (USG) ≤1.020, mild 
to moderate proteinuria, glucosuria, casts, 
pyuria, hematuria, and tubular epithelial cells; 
variable bacteriuria and crystalluria.
• Metabolic acidosis—mixed disorders may 
occur.
• Leptospirosis testing.
• Ethylene glycol testing.
• Canine pancreatic lipase immunoreactivity 
(cPLI) for pancreatitis.
IMAGING
• Survey and contrast radiography—kidneys 
normal to large with smooth contours; 
asymmetric in cats (“big kidney–little kidney” 
syndrome) with ureteral obstruction, uroliths 
may be seen.
• Antegrade nephropyelography for ureteral 
• Ultrasonography—evidence of pancreatitis, 
marked cortical hyperechogenicity may suggest 
ethylene glycol toxicity. Moderate cortical 
hyperechogenicity suggests glomerulonephritis 
or nephrosis. Pelvic and/or ureteral dilation 
may suggest outflow obstruction.
• Monitor urine output (UOP): anuria 
(≤0.25 mL/kg/h), oliguria, polyuria (≥2 mL/
kg/h). Avoid urinary catheterization due to 
infection risk. Assess UOP with serial body 
weights, ultrasound bladder assessment, 
weigh bedding, etc.
• Fine­needle aspiration may diagnose 
lymphoma.
• Renal biopsy may help identify underlying 
cause and prognosticate recovery.
Nephrosis or nephritis, glomerulonephritis, 
calcium oxalate crystals, interstitial edema, 
and lack of interstitial fibrosis, variable 
tubular regeneration.
  TREATMENT
Inpatient management—eliminate inciting 
causes; discontinue nephrotoxic drugs; 
maintain hemodynamic stability; ameliorate 
life­threatening fluid imbalances, biochemical 
abnormalities, and uremic complications.
• Hypovolemia—correct estimated fluid 
deficits with balanced isotonic solution 
within 2–4 hours if patient condition 
permits; once hydrated, ongoing fluid 
requirements are provided by 5% dextrose for 
insensible losses (~20–25 mL/kg/day) and 
balanced electrolyte solution equal to sensible 
losses; avoid overhydration.
• Hypervolemia—stop fluid administration 
and eliminate excess fluid by diuretics or 
dialysis.

24 Blackwell’s Five-Minute Veterinary Consult  
A
• Monitor body weight and blood pressure 
several times daily and adjust fluids to 
maintain stable weight once rehydrated.
DIET
• Nutritional support should be provided 
within 3 days using moderately protein ­
restricted diets.
• Caloric and protein requirements supplied 
by blended renal diets, liquid enteral solutions, 
or formulated diets delivered by enteral 
feeding tube. Parenteral nutrition may be 
needed in some cases.
• Depending on inciting cause, prognosis for 
recovery of renal function is variable. Average 
recovery for all causes of AKI is 50%. Likelihood 
of some degree of persistent kidney damage.
• Potential for complications of treatment 
(e.g., fluid overload, pancreatitis, sepsis, and 
multiple organ failure); expense of prolonged 
hospitalization; options for continued care if 
conventional medical management fails 
(hemodialysis, peritoneal dialysis); zoonotic 
potential of leptospirosis.
• See Ureterolithiasis.
• Renal transplantation may provide long ­ 
term survival for cats with severe, nonrecov­
ered AKI.
Peritoneal or Hemodialysis
• Dialysis can stabilize the patient to allow 
time for renal recovery. Without, most 
oliguric patients die before sufficient renal 
repair occurs.
• Indications—oliguria or anuria, life ­threat­
ening fluid overload or acid ­base/electrolyte 
disturbances, BUN ≥100 mg/dL, serum 
creatinine ≥5 mg/dL, clinical course 
refractory to conservative treatment, peri ­ 
operative stabilization, and poisoning/
overdosage with dialyzable toxin/drug.
Inadequate Urine Production
• Avoid overhydration. Once fluid replete, 
administer diuretics.
• Hypertonic mannitol (20%)—0.5 g/kg IV 
over 15–30 minutes; if effective, continue IV 
bolus q6h.
• Furosemide—1–4 mg/kg IV; if effective, 
continue at 0.5 mg/kg/h or 2 mg/kg q6h.
• Dopamine—potential side effects and lack 
of efficacy contraindicate its use except for 
pressor control. Fenoldopam may be more 
efficacious.
• Dialysis for refractory cases.
Metabolic Disorders, Acid-Base 
Disorders
Administer bicarbonate if serum bicarbonate 
≤16 mEq/L; bicarbonate replacement: mEq = 
bicarbonate deficit × body weight (kg) × 0.3; give half IV over 30 minutes and remainder 
over 2–4 hours, then reassess.
Hyperkalemia
• Correct dehydration with potassium ­free 
fluids.
• Minimize potassium intake.
• Discontinue medications that promote 
hyperkalemia.
• Loop diuretics—furosemide 1–2 mg/kg IV.
• Sodium bicarbonate—correct bicarbonate 
deficit, if bicarbonate status unknown 
1–2 mEq/kg IV.
• Dextrose ± insulin—1–2 mL/kg of 50% 
dextrose diluted to 25% IV or regular insulin 
0.1–0.2 U/kg IV bolus followed by 1–2 g 
dextrose/unit insulin.
• Calcium gluconate 10%—0.5–1.0 mL/kg 
IV over 10–15 minutes (cardioprotective, 
does not alter serum potassium).
• Refractory hyperkalemia—dialysis.
Vomiting
• Reduce gastric acid production—
pantoprazole (1 mg/kg IV q12h), 
famotidine CRI.
• Mucosal protectant for gastrointestinal (GI) 
ulceration—sucralfate (0.25–1 g PO q6–8h).
• Antiemetics—maropitant (1 mg/kg SC/IV 
q24h); ondansetron (0.2–1 mg/kg IV q8–12h).
Modify dosages of drugs requiring renal 
metabolism or elimination.
  FOLLOW-UP
Fluid, electrolyte, and acid ­base balances; body 
weight; blood pressure; UOP; and clinical status.
• Anticipate AKI in aged patients or those 
with systemic disease, sepsis, trauma, hemo ­ 
dynamic instability, receiving nephrotoxic 
drugs, multiple organ failure, or undergoing 
prolonged anesthesia.
• Monitor urine production, BUN, and 
creatinine in high ­risk patients.
Seizures, coma, cardiac arrhythmias, hypo ­ or 
hypertension, congestive heart failure, pulmonary 
edema, uremic pneumonitis, GI bleeding, sepsis, 
cardiopulmonary arrest, and death.
• Prognosis depends on underlying cause, 
extent of renal injury, concomitant disease or 
organ failure, and response to therapy.
• Survival rate ~50%, but depends on cause: 
<20% for advanced ethylene glycol toxicosis, 
>80% for acute leptospirosis.
• Polyuric AKI—typically milder than 
oliguric; recovery may occur over 2–6 weeks, 
but prognosis remains guarded.
• Oliguric AKI—extensive kidney injury, 
difficult to manage, and has poor prognosis 
for recovery without dialysis; recovery may be signaled by sudden (and often excessive) polyuria 
and sluggish and possibly incomplete return of 
renal function over 4–12 weeks; dialysis extends 
potential for renal regeneration and repair.
• Anuric AKI—poor prognosis without 
dialysis. Anuria is not prognostic and does 
not impact ability for renal recovery, if 
hemodialysis is available to maintain patient 
during recovery period.
Leptospirosis
A rare complication of pregnancy; promoted 
by acute metritis, pyometra, and postpartum 
sepsis or hemorrhage.
SYNONYMS
• Acute renal failure.
• Acute tubular necrosis.
• Acute uremia.
SEE ALSO
• Hypertension, Systemic Arterial.
• Leptospirosis.
• Ureterolithiasis.
• ACEI = angiotensin ­converting enzyme 
inhibitors.
• AKI = acute kidney injury.
• CKD = chronic kidney disease.
• cPLI = canine pancreatic lipase 
immunoreactivity.
• DIC = disseminated intravascular 
coagulation.
• NSAID = nonsteroidal anti ­inflammatory 
drug.
• UOP = urine output.
• USG = urine specific gravity.
Cowgill LD, Langston C. Acute kidney 
insufficiency. In: Bartges J, Polzin DJ, eds., 
Nephrology and Urology of Small Animals. 
Ames, IA: Wiley ­Blackwell, 2011, 
pp. 472–523.
Sykes JE, Hartmann K, Lunn KF , et al. 2010 
ACVIM small animal consensus statement 
on leptospirosis: diagnosis, epidemiology, 
treatment, and prevention. J Vet Intern 
Med 2011, 25(1):1–13.
Authors  Sheri Ross and Cedric P . Dufayet
available onlineAcute Kidney Injury  (continued)

Canine and Feline, Seventh Edition  25
A Acute Respiratory Distress Syndrome
  BASICS
• Acute respiratory distress syndrome (ARDS) 
is a syndrome of acute onset of respiratory 
failure typified by diffuse bilateral pulmonary 
infiltrates on a dorsoventral thoracic radiograph, 
with no clinical evidence of left atrial 
hypertension or volume overload. ARDS 
results from an overwhelming inflammatory 
reaction in the alveolocapillary membrane in 
response to a systemic or pulmonary inflamm­
atory insult. The end result is increased 
vascular permeability leading to edema. • The 
2012 Berlin Definition of ARDS defines three 
categories of severity based on PaO2/FiO2 (PF) 
ratio and level of positive end‐expiratory 
pressure (PEEP) employed during ventilation, 
with mild ARDS defined by a PF ratio of 
200–300 mmHg with PEEP ≥5 mmHg, 
moderate ARDS as a PF ratio of 100–
200 mmHg with PEEP ≥5 mmHg, and severe 
ARDS as a PF ratio <100 mmHg with PEEP 
≥5 mmHg.
• ARDS is due to a diffuse inflammatory insult 
that causes widespread damage to alveolar 
endothelial and epithelial cells, resulting in 
thickening of the membrane and impaired gas 
exchange. This inflammatory insult can be 
triggered by primary pulmonary disease or it 
can be of nonpulmonary origin, and leads to 
exudative, proliferative, and fibrotic changes 
within the lung. • First, excessive accumulation 
and activation of neutrophils, monocytes, and 
platelets in the pulmonary microvasculature 
lead to increased alveolar endothelial 
permeability. This causes protein‐rich edema 
fluid and inflammatory cells to leak into the 
interstitial and alveolar spaces. • Alveolar 
epithelial injury results from release of cytokines 
and other inflammatory mediators from 
leukocytes and platelets. • Epithelial injury 
involves both type I and type II alveolar 
epithelial cells, and results in alveolar flooding 
and surfactant dysfunction. This causes collapse 
and consolidation of alveoli with development 
of severe hypoxemia, and hyaline membrane 
formation in the alveolar spaces. 
• Microthrombi in the pulmonary vasculature, 
hypoxic pulmonary vasoconstriction, and 
release of endogenous vasoconstrictors lead to 
pulmonary arterial hypertension, which can 
lead to right‐sided heart failure. • Proliferation 
of type 2 alveolar epithelial cells and pulmonary 
fibrosis occurs in the late stages of ARDS.
• Respiratory. • Cardiovascular—right‐sided 
heart failure secondary to pulmonary hyper  ­ 
tension; hemodynamic compromise may be 
associated with aggressive mechanical 
ventilator settings.GENETICS
Certain humans are more prone to develop­
ing ARDS than others due to specific gene 
polymorphisms. This has not been investi­
gated in the veterinary population.
Unknown
Species
A familial form of ARDS has been reported 
in a group of related Dalmatian dogs; it is 
clinically indistinguishable from ARDS.
Unknown
SIGNS
• Acute onset of respiratory distress in patient 
with significant underlying disease or exposure to 
known risk factors. • Patient often hospitalized 
for primary disease when develops ARDS.
• Severe respiratory distress. • Crackles (if 
present) heard bilaterally on auscultation. 
• Fever—depends on underlying disease. 
• Cyanosis in more severe cases. • Signs 
relevant to primary disease process.
CAUSES
Primary Pulmonary Causes
• Aspiration pneumonia. • Pneumonia. 
• Pulmonary contusion. • Near drowning. 
• Chemical or smoke inhalation. • Idiopathic 
form of ARDS associated with acute interstitial 
pneumonia or idiopathic pulmonary fibrosis 
has been reported in humans and dogs.
Nonpulmonary Causes
• Systemic inflammatory response syndrome 
(SIRS). • Sepsis. • Neoplasia. • Pancreatitis. 
• Severe trauma and shock. • Severe bee sting 
envenomation.
• SIRS. • Sepsis. • Severity of illness. • Multiple 
transfusions.
  DIAGNOSIS
• Left‐sided congestive heart failure. • Fluid 
overload. • Diffuse pneumonia. • Pulmonary 
hemorrhage.
• Leukocytosis or leukopenia. • Other changes 
dependent on underlying disease process.
• Arterial blood gases—low PF ratio (where 
PaO2 is measured in mmHg and FiO2 is 0.21–1.0). Normal PF ratio = 500; comparison 
of this ratio allows evaluation of severity of lung 
disease and direct comparison of blood gases 
taken at different FiO2. PaCO2 is often low; 
hypercapnia tends to be late (preterminal) 
development. • Total protein of airway edema 
fluid compared with serum total protein—ratio 
of edema fluid to serum total protein <0.5 
supportive of low‐protein hydrostatic pressure 
pulmonary edema (e.g., heart failure, fluid 
overload); edema fluid/serum total protein ratio 
>0.7 suggests high‐protein, increased permeability 
pulmonary edema such as ARDS and 
pneumonia. • Coagulation panel may reveal 
hypocoagulable state supportive of 
disseminated intravascular coagulation (DIC) 
or cause of pulmonary hemorrhage.
IMAGING
Thoracic Radiographs
• Bilateral/diffuse pulmonary infiltrates. 
• Severity of radiographic signs can lag behind 
clinical disease by 12–24 hours. • Can be 
difficult to distinguish from cardiogenic edema; 
cardiac silhouette and pulmonary vascular size 
usually normal in ARDS.
Echocardiography
• Attempt to rule out cardiogenic cause for 
pulmonary edema. • May be able to estimate 
degree of pulmonary hypertension.
Pulmonary artery catheter to measure 
pulmonary artery occlusion pressure can be used 
to rule out cardiogenic cause for edema; by 
definition, ARDS is associated with pulmonary 
artery occlusion pressure (PAOP) ≤18 mmHg.
Gross Pathology
Lungs are dark, heavy, and ooze fluid when cut.
Histopathology
• Acute phase—pulmonary vascular congestion 
with edema fluid and inflammatory cell 
accumulation in interstitium and alveoli; 
epithelial cell damage, hyaline membrane 
formation, microthrombi, microatelectasis. 
• Proliferative phase—hyperplasia of type 2 
pneumocytes, interstitial mononuclear 
infiltration, organization of hyaline membranes, 
and fibroproliferation.
  TREATMENT
• No specific therapy; general aims to maintain 
tissue oxygenation and minimize iatrogenic lung 
injury while treating underlying disease. 
• Oxygen therapy—no more than required to 
maintain PaO2 >60–80 mmHg to minimize 
oxygen toxicity. • Positive‐pressure ventilation 
(PPV) essential in management of ARDS patients; 
indicated in patients that are hypoxemic despite

26 Blackwell’s Five-Minute Veterinary Consult  
A
oxygen therapy, patients requiring high levels of 
inspired oxygen for prolonged periods, or 
patients working so hard to breathe that at risk 
of exhaustion. • ARDS thought to be 
exacerbated by ventilator‐induced lung injury 
associated with alveolar overdistension 
compounded by cyclic opening and collapse of 
atelectatic alveoli; therefore, lung‐protective 
strategies of PPV with moderate to high PEEP , 
low tidal volumes, and permissive hypercapnia 
recommended to minimize ventilator‐induced 
lung injury; tidal volumes of 6 mL/kg have been 
found to increase survival significantly in human 
ARDS patients compared to tidal volumes of 
12 mL/kg. • Recruitment maneuvers and high 
levels of PEEP can both cause significant 
hemodynamic compromise and patients should 
have constant direct arterial blood pressure 
monitoring. • Intensive supportive care of 
cardiovascular system and other organ systems is 
vital, as these patients at high risk for development 
of multiple organ dysfunction.
• Monitor temperature closely, especially if 
using an oxygen cage, as animals with excessive 
work of breathing can easily become hyper  ­ 
thermic. • Ventilator patients require frequent 
position changes and physical therapy; regular 
oral care with dilute chlorhexidine solution is 
important to reduce oral colonization with 
bacteria as source of sepsis, and frequent 
endotracheal tube suctioning needed to prevent 
occlusion; inflate cuff carefully and change 
endotracheal cuff position regularly to prevent 
tracheal damage. • Blood pressure monitoring, 
as septic patients prone to hypotension. • Fluid 
therapy important to support cardiovascular 
system and maintain normovolemia while 
avoiding fluid overload, as this will negatively 
affect lung function.
ACTIVITY
If not anesthetized for ventilation, strict cage 
confinement.
DIET
Nutritional support important but challenging. 
Enteral feeding desired over parenteral nutrition, 
but must consider high risk of regurgitation and 
aspiration in recumbent patient.
Clients need to be aware of the guarded 
prognosis and high costs of therapy.
Underlying disease may require surgery.
• No specific drug therapy. • Antibiotics for 
underlying disease where indicated. • Vasoactive drugs to maintain blood 
pressure. • Anesthetic drugs to allow PPV. 
• Analgesia as appropriate. • Low‐dose 
corticosteroid—use remains controversial, 
with conflicting reports of efficacy for low‐
dose steroids in early or late ARDS.
Furosemide may produce pulmonary venous 
dilation and improve lung function, as 
intermittent bolus of 1 mg/kg IV q6–12h or 
as CRI of 0.2 mg/kg/h IV. Beware dehydra­
tion and effects on organ function.
  FOLLOW‐UP
Arterial blood gases, pulse oximetry, end‐tidal 
carbon dioxide, thoracic radiographs, arterial 
blood pressure, ECG, temperature, urine 
output, CBC, coagulation profiles, serum 
chemistry, blood cultures, monitoring for 
other organ dysfunction.
• Appropriate therapy of primary disease 
processes to reduce inflammatory insult 
to lung. • Intensive cardiovascular 
monitoring and support of critically ill 
animals to ensure adequate tissue perfusion. 
• Careful management of recumbent animals 
to reduce chance of aspiration, especially if 
patient has neurologic disease or upper 
airway disorders that reduce ability to protect 
airway. • Judicious use of blood products in 
patients with inflammatory or severe 
systemic disease.
• Multiorgan dysfunction syndrome—acute 
kidney injury, DIC, and gastrointestinal 
disease are more common forms of organ 
dysfunction seen. • Barotrauma—can result 
in pneumothorax; incidence thought to be 
less with lower tidal volume ventilation 
strategies. • Ventilator‐associated pneumonia—  
patients on PPV have increased risk of 
pneumonia that may be difficult to 
differentiate from worsening of initial lung 
injury; airway cultures should be considered 
in deteriorating patients. • Oxygen toxicity 
may be unavoidable due to severity of 
hypoxemia in spite of PPV; oxygen toxicity 
indistinguishable from ARDS on 
histopathology, making incidence of this 
problem impossible to determine.
• Mortality in human patients remains at 
40–60%. • Mortality in veterinary patients is 
likely greater than 90%.  MISCELLANEOUS
SIRS, multiple organ dysfunction syndrome, 
sepsis.
SYNONYMS
• Acute hypoxemic respiratory failure. • Acute 
interstitial pneumonia. • Adult respiratory 
distress syndrome. • High‐protein pulmonary 
edema. • Shock lung.
SEE ALSO
• Dyspnea and Respiratory Distress. • Panting 
and Tachypnea. • Pulmonary Edema, 
Noncardiogenic. • Sepsis and Bacteremia.
• ARDS = acute respiratory distress syndrome. 
• DIC = disseminated intravascular coagulation. 
• PAOP = pulmonary artery occlusion pressure 
(formerly pulmonary capillary wedge pressure). 
• PEEP = positive end‐expiratory pressure.  
• PF ratio = PaO2/FiO2 ratio. • PPV = 
positive‐pressure ventilation. • SIRS = systemic 
inflammatory response syndrome.
www.ardsnet.org
ARDS Definition Task Force, Ranieri VM, 
Rubenfeld GD, et al. Acute respiratory 
distress syndrome: the Berlin Definition. 
J Am Med Assoc 2012, 
307(23):2526–2533.
Balakrishnan A, Drobatz KJ, Silverstein DC. 
Retrospective evaluation of the prevalence, 
risk factors, management, outcome, and 
necropsy findings of acute lung injury and 
acute respiratory distress syndrome in dogs 
and cats: 29 cases (2011–2013). J Vet 
Emerg Crit Care 2017, 27(6):662–673.
Matthay MA, Ware LB, Zimmerman GA. 
The acute respiratory distress syndrome. 
J Clin Invest 2012, 122(8):2731–2740.
Parent C, King LG, Van Winkle TJ, Walker 
LM. Respiratory function and treatment in 
dogs with acute respiratory distress 
syndrome: 19 cases (1985–1993). J Am Vet 
Med Assoc 1996, 208:1428–1433.
Ware LB, Matthay MA. The acute respiratory 
distress syndrome. N Engl J Med 2000, 
342:1334–1349.
Wilkins PA, Otto CM, Baumgardner JE, et al. 
Acute lung injury and acute respiratory distress 
syndromes in veterinary medicine: consensus 
definitions: The Dorothy Russell Havemeyer 
Working Group on ALI and ARDS in 
Veterinary Medicine. J Vet Emerg Crit Care 
(San Antonio) 2007, 17(4):333–339.
Author  Casey J. Kohen
Consulting Editor  Elizabeth RozanskiAcute Respiratory Distress Syndrome  (continued)

Canine and Feline, Seventh Edition  27
A Acute Vomiting
  BASICS
Vomiting of fewer than 7 days’ duration.
• Vomiting is a reflex initiated by the 
vomiting center in the medulla, triggered by 
three major mechanisms—gastric/duodenal 
mucosal irritation, gastric/duodenal distention, 
or the chemoreceptor trigger zone (CRTZ). 
• Mucosal irritation or gastric/duodenal 
distention signal the vomiting center via 
sympathetic and vagal afferent innervation. 
Anti-peristaltic waves force intestinal contents 
back to the duodenum, then distention 
becomes the main trigger for the vomiting 
reflex. • The CRTZ can directly trigger the 
vomiting center via receptor activation or 
vestibular input; known receptors are α2, D2, 
H1, M1, NK1, 5HT3. • Cerebral cortex and 
vestibular apparatus can also directly stimulate 
the vomiting center. • The vomiting center 
initiates an autonomic motor reaction via 
spinal nerves to diaphragmatic and abdominal 
muscles, and cranial nerves 5, 7, 9, 10, and 12 
to the upper gastrointestinal (GI) tract. • The 
reflex involves a deep breath, opening the 
upper esophageal sphincter, closing the glottis, 
strong diaphragmatic and abdominal muscle 
contractions, and lower esophageal sphincter 
relaxation, leading to expulsion of contents.
with progressive dehydration to hypovolemia; 
vagal stimulation can lead to bradycardia, and 
rarely syncope. • GI—esophagitis. • Metabolic—  
vomiting of mixed small intestinal and gastric 
contents results in isotonic electrolyte losses; 
pyloric obstruction results in metabolic alkalosis; 
hypokalemia is common with concurrent 
hyporexia. • Respiratory—aspiration 
pneumonitis/pneumonia.
GENETICS
N/A
Increased incidence of infectious causes and 
dietary indiscretion in young patients.
• Species—dog and cat. • No breed, age, or 
sex predilections.
SIGNS
• Care should be taken to differentiate 
vomiting from regurgitation. • Dietary 
indiscretion, foreign body, and medication/toxin history should be investigated. • Nausea 
and hypersalivation. • Varying amounts, 
frequency, and severity of vomiting. • Varying 
activity levels can be seen, from normal to 
lethargic. • Hematemesis may be seen.
• Dehydration/hypovolemia, cranial 
abdominal pain, nausea, fluid–gas interface 
on intestinal palpation, increased borborygmi. 
• Careful sublingual examination for 
anchored linear foreign bodies. • Careful 
abdominal palpation for mechanical 
obstruction. • Rectal examination for melena 
or concurrent diarrhea.
CAUSES
disease, kidney disease, pancreatitis, neoplasia 
(non-GI). ◦ Uncommon—CNS, cardiac, 
endocrine (hypoadrenocorticism, hyper -
thyroidism, diabetic ketoacidosis), respiratory 
disease, peritonitis, sepsis. ◦ Intra-GI causes: 
◦ Congenital/genetic—hiatal hernia.  
◦ Infectious—parasitic, protozoal, viral 
(parvovirus, canine distemper virus, corona 
virus), fungal, bacterial ( Campylobacter , 
Salmonella ). ◦ Inflammatory (most common 
cause)—acute gastritis/gastroenteritis due to 
dietary indiscretion or sudden diet change, 
acute hemorrhagic diarrhea syndrome. 
◦ Mechanical obstruction—foreign body, 
intussusception, obstructive mass (granuloma, 
neoplasia, pyloric hypertrophy, trichobezoar), 
torsion/volvulus (gastric, mesenteric). 
◦ Medications/toxins— α2 agonists, antibiotics, 
apomorphine, chemotherapeutic agents, 
methimazole, nonsteroidal anti-inflammatory 
drugs (NSAIDS), opioids, toxins (corrosive, 
heavy metals). ◦ Neoplasia—primary such as 
adenocarcinoma, lymphoma, leiomyoma/
leiomyosarcoma, gastrointestinal stromal 
tumor, mast cell tumor (cats), metastatic. 
◦ Ulcers—gastric and/or duodenal ulceration is 
usually secondary: NSAIDS, neoplasia (primary 
GI, mast cell tumor, gastrinoma), hypoadreno -
corticism, uremia, infectious (controversial—
Helicobacter ), stress.
indiscretion. • Medications—many medic -
ations can cause acute vomiting. • Infectious—  
geographic distribution effect.
  DIAGNOSIS
• Vomiting can be mistaken for regurgitation. 
◦ Vomiting—prodromal nausea (hypersaliva -
tion), retching, abdominal contractions. 
◦ Regurgitation—no prodromal nausea, passive 
expulsion of fluid/food. ◦ Vomiting can lead to regurgitation via esophagitis, so if both signs are 
present, it is important to establish chronology. 
• In cats, vomiting can be mistaken for coughing. 
◦ Coughing involves extension of neck and 
elbows. ◦ Physical exam findings may differenti -
ate. ◦ Videos can be helpful to differentiate.
• Extra-GI causes: ◦ Increased hepatic enzyme 
activity in hepatobiliary diseases. ◦ Renal 
azotemia in kidney disease. ◦ Increased 
hepatic enzyme activity, hypoalbuminemia, 
in hypoadrenocorticism. • Intra-GI causes—
often normal. • As result of vomiting, 
following may be present: ◦ Hemoconcentration. 
◦ Prerenal azotemia. ◦ Hypokalemia, 
hypochloremia. ◦ Hypoalbuminemia, 
hypocholesterolemia. ◦ Hypoglycemia—  
toy-breed puppies predisposed.
• Extra-GI interrogation—baseline cortisol or 
adrenocorticotropic hormone (ACTH) 
stimulation test in dogs, T4 in cats, quantitative 
pancreatic lipase immunoreactivity. • Intra-GI 
interrogation—fecal flotation, fecal direct 
smear cytology.
IMAGING
• Survey abdominal radiographs indicated in 
most acutely vomiting patients to evaluate 
potential surgical emergencies, like mechanical 
obstructions and sepsis. Survey abdominal 
radiographs also interrogate many extra-GI 
causes of vomiting. • Acute gastritis/gastro  - 
enteritis—mild gas and/or fluid dilation of 
stomach/intestine. • Mechanical obstruction—
foreign body may be radiopaque, or two 
populations of bowel may be seen, one 
distended orad to the obstruction, and one 
normal aborad to the obstruction. • If foreign 
body is suspected, but no radiographic 
evidence, serial radiographs every 6 hours or 
contrast radiography may be considered. 
• Gastric dilatation and volvulus—
malpositioned pylorus on right lateral 
radiograph. • Pancreatitis—widened gastro -
duodenal angle, focal decreased serosal detail at 
proximal duodenal flexure.
of vomiting, such as pancreatitis and 
intussusception. • Emergency cage-side 
focused ultrasonographic examination of 
abdomen is indicated in patients with acute 
abdominal pain, to evaluate for etiologies that 
are surgical emergencies, such as septic or bile 
peritonitis. • If peritoneal effusion seen, 
abdominocentesis and immediate in-house 
cytology are indicated (+/- culture).

28 Blackwell’s Five-Minute Veterinary Consult  
A
• Endoscopy rarely indicated in acute 
vomiting, except for gastric foreign bodies or 
gastric ulceration. • Exploratory celiotomy 
may be considered with high suspicion for 
mechanical obstruction, even when not 
confirmed with imaging.
  TREATMENT
• Stable patients, mild vomiting—outpatient 
hypovolemic or acute abdominal pain—
inpatient medical care. • Emergency surgery 
may be indicated—mechanical obstruction, 
septic or bile peritonitis, volvulus.
perfusion status. • Most patients with 
dehydration/hypovolemia need isotonic 
crystalloids to replenish losses and provide 
maintenance. • Nothing PO—only indicated 
in patients with mechanical obstruction, 
severe intractable vomiting, or patients with 
high risk of aspiration.
ACTIVITY
Activity restriction only required in 
postoperative care of surgical patients.
DIET
Once vomiting resolves, gradual 
reintroduction of small amounts of water, 
then small, frequent meals of bland, highly 
digestible diet is indicated for 3–5 days, then 
gradual reintroduction of patient’s routine 
diet and feeding schedule.
gradual diet changes, and foreign body 
avoidance may be appropriate.
Surgery may be indicated to treat etiology, 
such as mechanical obstruction.
• Anti-emetics not usually needed for mild 
acute vomiting, but may be needed in more 
severe cases—5HT3 antagonists such as 
ondansetron (0.2–1 mg/kg SC/IV q8h), NK1 
antagonist maropitant (1 mg/kg SC q24h or 
2 mg/kg PO q24h), dopamine antagonist and 
prokinetic metoclopramide (0.2–0.5 mg/kg SC/PO q6–8h, or 1–2 mg/kg/day as CRI), 
phenothiazine derivative chlorpromazine 
(0.5 mg/kg SC q8h). • Refractory vomiting 
patients (i.e., pancreatitis) may need multi -
modal anti-emetics that act on different 
receptors. • Gastric/duodenal ulcers—proton 
pump inhibitor such as pantoprazole IV or 
omeprazole PO (1 mg/kg IV/PO q12h) is 
preferred treatment. Sucralfate, while used 
conventionally in ulcers, has only been shown 
to help cats with esophagitis, and due to 
impaired absorption of concurrently given 
medications, and q8 dosing, is of questionable 
efficacy. • NSAID-induced ulceration—
consider misoprostol. • Vestibular mediated—
H1 antagonist like diphenhydramine (2–4 mg/
kg PO/IM q6–8h).
• Prokinetic medications should not be given to 
patients with mechanical obstruction. 
• Phenothiazine derivatives—caution in patients 
with seizures or hypovolemia/hypotension. 
• Anticholinergics should not be given, as 
exacerbation of signs from ileus can result.
Anti-emetic medications should not be given 
to patient receiving outpatient care, unless 
mechanical obstruction has been ruled out.
Ondansetron IV can react with other 
medications and precipitate.
Dolasetron, famotidine.
  FOLLOW-UP
• If patient receives anti-emetic with 
outpatient medical care, and continues to 
vomit—hospitalize for further diagnostics 
and inpatient medical care. • If vomiting not 
improving, or getting more severe, further 
diagnostics are warranted. • If vomiting 
persists beyond 7 days or recurs despite 
appropriate therapy, consider chronic 
vomiting etiologies.
• Aspiration pneumonia. • Esophagitis.
• Dehydration and hypovolemia.
• Mild acute vomiting from acute gastritis/
gastroenteritis usually self-limiting. 
• Mechanical obstruction from foreign bodies 
has good prognosis with rapid recognition 
and treatment. • Other prognoses etiology 
dependent.  MISCELLANEOUS
Acute diarrhea, hyporexia.
Younger patients more likely to have ingested 
foreign body or have infectious etiologies.
(Ancylostoma , Campylobacter , Giardia , Salmonella ).
Misoprostol for treatment of NSAID-induced 
ulcers is contraindicated in pregnant animals 
and humans.
SYNONYMS
Emesis
SEE ALSO
• Acute Diarrhea. • Gastroduodenal 
Ulceration/Erosion. • Gastroenteritis, Acute 
Hemorrhagic Diarrhea Syndrome. 
• Pancreatitis – Cats. •  Pancreatitis – Dogs. 
• Vomiting, Chronic.
• ACTH = adrenocorticotropic hormone.
• CRTZ = chemoreceptor trigger zone.  
• GI = gastrointestinal. • NSAID = 
nonsteroidal anti-inflammatory drug.
Gallagher A. Vomiting and regurgitation. In: 
Ettinger SJ, ed., Textbook of Veterinary 
Internal Medicine, 8th ed. St. Louis, MO: 
Elsevier, 2017, pp. 158–164.
ACVIM consensus statement: support for 
Unterer S, Busch K, Leipig M, et al. 
Endoscopically visualized lesions, histologic 
findings, and bacterial invasion in the 
gastrointestinal mucosa of dogs with acute 
hemorrhagic diarrhea syndrome. J Vet 
Intern Med 2014, 28:52–58.
acknowledge the prior contribution of Erin 
Portillo.
available onlineAcute Vomiting  (continued)

Canine and Feline, Seventh Edition  29
A Adenocarcinoma, Anal Sac
  BASICS
Malignant neoplasm derived from the 
apocrine glands of the anal sac.
• Locally invasive.
• High metastatic rate (~50–80% at diagnosis), 
often to locoregional lymph nodes including 
medial iliac (MILN), internal iliac, sacral, less 
frequently to distant sites including liver, 
spleen, or lungs.
• Frequently associated with hypercalcemia, 
secondary to parathyroid hormone–related 
peptide (PTH-rP) secretion.
• Prognosis good to guarded with appropriate 
treatment intervention.
• Gastrointestinal.
• Endocrine/metabolic.
• Hemic/lymphatic/immune.
GENETICS
English cocker spaniels significantly over  - 
represented, springer and Cavalier King 
Charles spaniels also overrepresented.
Relatively uncommon—17% of perianal 
tumors, 2% of all skin/subcutaneous tumors.
• Older dogs; extremely rare in cats.
• Females overrepresented in some studies.
• Breed predilection as stated above.
SIGNS
Signs may be due to physical presence of 
primary tumor (visible mass near anus, 
tenesmus, scooting behaviors) or lymph 
nodes enlarged due to metastasis (tenesmus, 
obstipation, stranguria), or systemic 
manifestations due to hypercalcemia 
(polyuria/polydipsia, anorexia).
• Mass associated with anal sac; may be quite 
small relative to significant metastatic disease 
burdens.
• Caudal abdominal lymphadenopathy—on 
rectal or abdominal palpation.
None definitively identified.
  DIAGNOSIS
• Anal sac abscess.
• Perianal adenoma/adenocarcinoma.• Mast cell tumor.
• Melanoma.
• Lymphoma.
• Squamous cell carcinoma.
• Perineal hernias.
• Hypercalcemia—15–30% of cases; 
associated hyposthenuria.
• Secondary renal failure may develop with 
longstanding and severe hypercalcemia. 
Beware of interpreting urine specific gravity 
to differentiate prerenal versus renal azotemia  
in hypercalcemic patients. Hypercalcemia 
inhibits concentrating abilities of kidneys, 
thus azotemia with dilute urine may be seen 
with both prerenal and renal azotemia. 
T reatment of disease to resolve hypercalce -
mia and fluid therapy is needed to determine 
if underlying renal pathology is present.
If hypercalcemia is present, and tumor cannot 
be identified, parathyroid hormone and 
PTHrP levels can be assessed—high PTHrP 
supports neoplasia as cause of hypercalcemia. 
This ancillary screening test is not commonly 
required, as anal gland tumors are easily 
palpable.
IMAGING
• Abdominal radiography—to evaluate 
medial iliac lymph nodes and lumbar and 
pelvic bones.
• Thoracic radiography—to evaluate for 
pulmonary metastasis.
• Abdominal ultrasonography—may 
identify enlarged locoregional lymph nodes 
not visible radiographically, and also 
metastatic lesions involving visceral organs 
(liver/spleen).
• CT scan—identifies lymphadenopathy with 
greater sensitivity than ultrasound. In one 
study ultrasound found all affected lymph 
nodes in only 30.8% of cases where CT 
identified multiple nodes involved.
• Fine-needle aspiration and cytology of anal 
sac mass to rule out conditions other than 
adenocarcinoma; while differentiation of 
benign versus malignant neoplasm of perianal 
masses is difficult, apocrine gland adenocarci-
noma of anal sac will have neuroendocrine 
appearance and can be differentiated from 
perianal gland tumors.
• Fine-needle aspiration and cytology of 
enlarged lymph nodes, liver, or splenic 
nodules to confirm metastasis.
• Histopathology required for definitive 
diagnosis. Incisional biopsy can be consid-
ered, but excisional biopsy appropriate if 
location of mass and cytology supportive of 
anal sac neoplasia.  TREATMENT
• Surgical resection is treatment of choice.
• Resection of primary tumor and enlarged 
lymph nodes prolongs survival—both at 
initial diagnosis and upon relapse.
• If mass is large and locally invasive at 
diagnosis, surgery will be palliative, not 
curative.
• Debulking all disease present may control 
hypercalcemia until tumor recurrence.
• Surgery may not be possible if primary 
mass is very large.
• Adjuvant radiation for microscopic disease 
may help delay local recurrence and evidence 
of lymph node metastases.
• Hypofractionated radiation can provide 
benefit in cases of advanced or inoperable 
disease, with about one-third of dogs showing 
partial response to radiation, and about 
two-thirds of dogs having improvement or 
resolution of their clinical signs.
• Saline diuresis (200–300 mL/kg/day) 
preoperatively if hypercalcemia is severe. Also 
can consider bisphosphonate (zoledronate, 
pamidronate) or low-dose (0.25 mg/kg BID) 
prednisone to increase calciuresis, if corticos-
teroids not contraindicated.
• Low-dose prednisone can also be used to 
manage hypercalcemia palliatively in dogs 
that are not receiving any other therapy.
• No controlled studies showing improved 
outcomes with adjuvant chemotherapy 
postoperatively; however, such studies fraught 
with challenges, including range of stages of 
presenting dogs and retrospective nature of 
most publications. Theoretically, systemic 
therapy needed to address the highly metastatic  
biologic behavior of this tumor.
• Limited reports of partial responses to 
platinum compounds in dogs—cisplatin 
(70 mg/m2 IV with 6h saline diuresis— 
18.3 mL/kg/h), carboplatin (300 mg/m2 IV 
as slow bolus) every 3 weeks.
• Mitoxantrone (5 mg/m2 IV every 3 weeks 
for five treatments) in combination with 
radiation therapy used in one small case 
series.
• Possible role for melphalan after debulking 
surgery (7 mg/m2 PO q24h for 5 days every 3 
weeks).
• Toceranib phosphate reported to have some 
benefit (partial response or stable disease) in 
28 dogs with measurable tumor. In 15 dogs 
with stage 4 (distant metastasis) disease,

30 Blackwell’s Five-Minute Veterinary Consult  
A
toceranib phosphate led to stable disease and 
modest improvement in clinical signs in 13 
dogs, with median progression-free interval 
and survival time of 1 year.
• Phase 1 trial combining carboplatin and 
toceranib phosphate in 11 dogs, 4 of which 
had apocrine adenocarcinoma of anal sac, identi  - 
fied combination of carboplatin (200 mg/m2 
IV every 3 weeks) and toceranib phosphate 
(~2.75 mg/kg PO every other day) to be well 
tolerated. Neutropenia was dose-limiting 
toxicity. All dogs with anal sac tumors 
responded, with 1 partial response and 3 
stable disease. Further studies are warranted.
• Use caution with platinum chemotherapeu-
tic agents in dogs with renal insufficiency.
• Do not use cisplatin in cats.
  FOLLOW-UP
• If complete resection was achieved—physi-
cal examination, thoracic radiography, 
abdominal ultrasonography, or abdominal 
+/– thoracic CT and serum biochemistry at 
3, 6, 9, and 12 months postoperatively, then 
every 6 months thereafter.
• Incomplete resection—frequency of and 
modalities for monitoring dependent on 
ancillary treatments selected. If further 
therapies declined, at minimum monitor 
tumor size, blood calcium, and renal values. If 
using adjuvant therapy, monitor based on 
specifics of therapy.EXPECTED COURSE AND PROGNOSIS
• Wide ranges of survivals reported. Many 
dogs do well with multiple surgeries with or 
without adjuvant therapies (chemotherapy, 
radiation therapy). Long-term prognosis is 
fair, with both local progression and 
metastasis occurring.
• Cures may occur if tumor is found early 
and treated aggressively—median survival 
time for nonmetastatic tumors <3.2 cm in 
largest diameter was 1,237 days.
• Growth of tumor may be slow and 
debulking lymph node metastatic disease 
burdens may significantly prolong survival.
• Hypercalcemia variably associated with 
poor prognosis, with some studies showing it 
as negative factor.
• Four papers (involving 200 dogs) showed 
median survival times of 6–20 months, 
depending on stage and treatment.
• Dogs with lymph node metastasis lived 
significantly longer if nodes were extirpated.
• Ultimately, dogs that cannot have their 
tumors excised completely succumb to 
hypercalcemia-related complications or mass 
effect from primary tumor or regional nodal 
metastases.
Hypercalcemia as paraneoplastic syndrome.
• MILN = medial iliac.
• PTHrP = parathyroid hormone-related 
peptide. Suggested Reading
Barnes DC, Demetriou JL. Surgical manage-
ment of primary, metastatic and recurrent 
anal sac adenocarcinoma in the dog: 52 
cases. J Small Anim Pract 2017; 58:263–268.
Elliott JW. Response and outcome following 
toceranib phosphate treatment for stage 
four anal sac apocrine gland adenocarci-
noma in dogs: 15 cases (2013–2017). J Am 
Vet Med Assoc 2019; 254:960–966.
McQuown B, Keyerleber MA, Rosen K, et al. 
T reatment of advanced canine anal sac 
adenocarcinoma with hypofractionated 
radiation therapy: 77 cases (1999–2013). 
Vet Comp Oncol 2017; 15:840–851.
Palladino S, Keyerleber MA, King RG, et al. 
Utility of computed tomography versus 
abdominal ultrasound examination to 
identify iliosacral lymphadenomegaly in 
dogs with apocrine gland adenocarcinoma 
of the anal sac. J Vet Intern Med 2016; 
30:1858–1863.
Pradel J, Berlato D, Dobromylskyj M, et al. 
Prognostic significance of histopathology in 
canine anal sac gland adenocarcinomas: 
preliminary results in a retrospective study 
of 39 cases. Vet Comp Oncol 2018; 
16:518–528.
Author  Laura D. Garrett
Consulting Editor  Timothy M. Fan
available onlineAdenocarcinoma, Anal Sac  (continued)

Canine and Feline, Seventh Edition  31
A
  BASICS
OVERVIEW
• Comprises >75% of primary pulmonary 
tumors in dogs and cats. • Strongest predictors 
of outcome: tumor grade, node involvement, 
clinical signs. • May metastasize. • May be 
associated with hypertrophic osteopathy.
Dogs
• 1% of all tumors. • Mean age of affected 
animals 10 yrs. • No sex predilection, though 
more females in some reports. • Medium to 
large breeds overrepresented.
Cats
• Rarer than in dogs. • Mean age of affected 
animals 11 yrs. • No breed predilection.
SIGNS
• Related to presence of lung mass:
◦ Nonproductive cough ( >50% dogs, ~40% 
cats). ◦ Dyspnea (may be related to pneumo­
thorax or pleural effusion). ◦ Tachypnea. 
◦ Hemoptysis. • Paraneoplastic signs: 
◦ Lameness—bone metastasis or hypertrophic 
osteopathy (dogs or cats), weight‐bearing lytic 
digit metastasis (cats).  ◦ Polyuria or polydipsia—
hypercalcemia or hyperadrenocorticism from 
ectopic production of adrenocorticotrophic 
hormone (ACTH). ◦ Fever.
• May be asymptomatic or lack respiratory 
signs ( ~25% dogs, 9% cats). • Tachypnea, 
dyspnea. • Fever. • Limb swelling. • Ascites, 
pleural effusion.
Some (controversial) evidence correlates risk 
to urban environment; secondhand environ­
mental tobacco smoke not definitively linked 
to primary lung cancer in dogs, though weak 
association seen in dogs with short and 
medium‐length noses.
  DIAGNOSIS
• Cytology of mass aspirate. • Tissue biopsy/
definitive resection.
• Granulomatous lesion (fungal, foreign body, 
parasitic). • Pulmonary abscess. • Other 
primary lung tumor: ◦ Squamous cell 
carcinoma. ◦ Sarcomas (osteo‐, chondro‐, 
lipo‐). • Metastatic lung tumor. • Pneumonia. 
• Asthma. • Pulmonary thromboembolism. 
• Congenital cyst. • Lung torsion/hematoma.
No specific abnormalities.OTHER LABORATORY TESTS
N/A
IMAGING
• Thoracic radiography—usually demonstrates 
focal, solitary, well‐circumscribed mass in dogs, 
often in caudal lung lobes; caudal lobes most 
common in cats, though radiographic patterns 
vary more and can include diffuse interstitial 
disease; radiographs must be performed in cats 
presenting with multiple digit tumors to screen 
for primary lung tumor (lung‐digit syndrome). 
• Ultrasonography—to obtain aspirate or biopsy 
specimen if mass in contact with chest wall, or 
evaluate abdomen for primary tumor. • CT—to 
assess surgical feasibility, lymphadenopathy (93% 
accuracy), metastatic disease; can see cavitated 
areas, irregular margins, bronchial invasion.
• Thoracocentesis with cytologic examination 
(for pleural effusion). • Cytology—transthoracic 
fine‐needle aspiration (83% agreement with 
histopathology). • Percutaneous tissue biopsy—
use T ru‐Cut instrument, not commonly 
performed. • Open lung biopsy—via thoraco­
tomy, or minimally invasive thoracoscopy.
• Adenocarcinoma—classified by location 
(bronchial, bronchiolar, bronchiolar‐alveolar, 
or alveolar) and degree of differentiation.
• Immunohistochemistry on biopsy for thyroid 
transcription factor‐1 (TTF‐1), surfactant 
protein A, and napsin A to confirm pulmonary 
carcinoma, especially adenocarcinoma. TTF‐1 
and napsin A can also be seen in thyroid tumors.
• Cats tend to have less differentiated tumors, 
corresponding to more aggressive behavior.
  TREATMENT
• Surgery—mainstay of treatment: partial or 
complete lobectomy with tracheobronchial 
lymph node biopsy or removal; thoracoscopic 
removal possible at limited centers and offers 
less postoperative morbidity. • Radiotherapy—
reports anecdotal, but certain patients may 
benefit. • Chemotherapy should be considered 
following surgery for tumors that are high 
grade, undifferentiated, and/or have nodal 
involvement, though no benefit confirmed. 
Intracavitary chemotherapy can be used to 
treat malignant pleural effusion.
• Chemotherapy—vinorelbine concentrates 
in lungs and responses have been seen. 
◦ Doxorubicin, cisplatin, carboplatin, 
mitoxantrone, vinorelbine, and/or vindesine: 
rational choices for primary or adjuvant 
therapy. ◦ Platinum‐based or gemcitabine chemotherapy may be superior. ◦ Toceranib 
phosphate (Palladia) has shown some anecdotal 
success. • Chemotherapy can be toxic; seek 
advice if unfamiliar with cytotoxic drugs.
• Doxorubicin—cardiotoxic, avoid in dogs 
with myocardial disease (arrhythmias); 
nephrotoxic in cats. • Cisplatin—do not give 
to cats (fatal); do not use in dogs with 
preexisting renal disease; never use without 
appropriate and concurrent diuresis.
  FOLLOW‐UP
• Serial thoracic radiographs—every 3 mths; 
administer minimum two cycles of chemo­
therapy before evaluating response. • Perform 
CBC (with any chemotherapy), biochemical 
analysis (cisplatin), and urinalysis (cisplatin) 
before each chemotherapy.
• Following diagnostic procedures or 
thoracotomy—pneumo‐ or hemothorax. 
• Resulting from chemotherapy—myelo­
suppression, fever, sepsis, nausea.
• Metastasis to tracheobronchial lymph 
nodes—single best prognostic indicator; 
median survival without metastasis approaches 
1 yr and with metastasis, 60 days. More 
common (75%) in cats. • Postoperative 
survival around 2 yrs in both cats and dogs if 
positive prognostic factors present, and ~1 yr 
overall in dogs, 4 mths overall in cats. 
• Other patient, tumor, and treatment factors 
positively influencing prognosis—complete 
surgical excision; size of primary tumor ( <5 cm); 
lack of metastasis; well‐differentiated cellular 
morphology on histopathology, lack of 
clinical signs prior to surgery. • Poor 
prognosis for cats with lung‐digit syndrome 
poor ( ~1 mth).
Chemotherapy not advised in pregnant animals.
• ACTH = adrenocorticotrophic hormone.
• TTF‐1 = thyroid transcription factor‐1.
Rissetto KC, Lucas P , Fan TM. An update on 
diagnosing and treating primary lung 
tumors. Vet Med 2008, 103(3):154.
Author  Kim A. Selting
Consulting Editor  Timothy M. FanAdenocarcinoma, Lung

32 Blackwell’s Five-Minute Veterinary Consult  
AAdenocarcinoma, Nasal
  BASICS
Malignant neoplasm involving the nasal 
cavity and paranasal sinuses.
Progressive local and regional invasion of the 
nasal cavity, paranasal sinuses, and surrounding 
tissues by neoplastic epithelial and glandular 
epithelial cells.
• Respiratory—congestion, epistaxis, 
mucopurulent nasal discharge, obstruction, 
dyspnea.
• Ophthalmic—exophthalmos, epiphora.
• Musculoskeletal—facial deformity.
• Nervous—seizures, altered mentation.
• In dogs, less than 2% of all tumors are nasal 
tumors.
• In dogs, adenocarcinoma more common 
than squamous cell carcinoma, chondro­
sarcoma, and other histologies, comprising 
31.5% of all nasal tumors.
• In cats, nasal tumors comprise <1% of all 
tumors. In cats, adenocarcinoma and 
lymphoma are most common.
Nasal adenocarcinomas are more commonly 
reported in urban areas.
• Dog and cat.
• Median age in dogs is 10 years and in cats 
is 13 years.
• In dogs, medium to large breeds affected 
more commonly, with possible overrepres­
entation of mesocephalic and dolichocephalic 
breeds.
SIGNS
• Intermittent and progressive history of 
unilateral to bilateral epistaxis and/or 
mucopurulent discharge that initially 
responds to antibiotic therapy (median 
duration 3 months).
• Sneezing and increased upper respiratory 
noises, including reverse sneezing.
• Open ­mouth breathing.
• Halitosis.
• Anorexia (more frequent in cats).
• Seizures (rare—secondary to invasion of 
cranial vault).
• Nasal discharge (blood, mucopurulent).
• Decreased or absent airflow in nasal 
passages (unilateral or bilateral).
• Facial deformity, exophthalmos, epiphora.
• Pain upon nasal or paranasal sinus 
palpation or upon opening mouth.
• Regional lymphadenomegaly (rare).• Abnormal mentation or other neurologic 
findings (rare).
CAUSES
Dolichocephalic morphology, p53 mutations, 
and cyclooxygenase ­2 (COX ­2) overexpression 
may all play a role.
Urban environment and secondhand smoke 
may be risk factors.
  DIAGNOSIS
• Other sinonasal tumors (e.g., squamous cell 
carcinoma, lymphoma, sarcomas, olfactory 
neuroblastoma).
• Intracranial neoplasia (in dogs or cats with 
neurologic signs).
• Viral infection—cats.
• Fungal infections, including aspergillosis 
(dogs) and cryptococcosis (cats).
• Bacterial sinusitis.
• Parasites (e.g., nasal mites).
• Foreign body.
• T rauma.
• Tooth root abscess and oronasal fistula.
• Coagulopathies (nasal tumors most often 
tend to be unilateral epistaxis; coagulopathy 
tends to be bilateral epistaxis).
• Systemic hypertension (nasal tumors most 
often tend to be unilateral epistaxis; hypertension 
• Occasional blood loss anemia.
• Cytologic examination—occasionally 
helpful (e.g., aspirates of subcutaneous mass if 
facial deformity).
• Coagulation profile to rule out coagulopathy.
• Blood pressure to rule out systemic 
hypertension.
IMAGING
• Survey skull radiography—not sensitive; 
may show asymmetric destruction of 
turbinates accompanied by soft tissue mass 
effect; may see fluid density in frontal sinuses 
secondary to outflow obstruction.
• Thoracic radiography—evaluate for lung 
metastasis (uncommon).
• CT or MRI best imaging method for local 
staging and observing integrity of cribriform 
plate or orbital invasion; also used for 
therapeutic planning.
• Oral examination under anesthesia.
• Rhinoscopy may permit visual observation 
of mass and aid biopsy.
• Tissue biopsy necessary for definitive 
diagnosis—biopsies may be performed blind, 
following advanced imaging, using pinch biopsy instrument including retroflex 
rhinoscopic biopsy of nasopharynx, cannula 
(closed suction), or hydropulsion techniques.
• Cytologic evaluation of regional lymph 
nodes to detect regional metastatic disease.
• Bilateral involvement and osteolysis common.
• Regional lymph node metastasis <10% at 
time of diagnosis, but up to 45% at necropsy.
  TREATMENT
• Radiation therapy is standard of care.
• Radiation therapy can be administered with 
curative intent (conventional definitive or 
stereotactic radiotherapy) or for palliation of 
clinical signs.
• Conventional definitive radiation involves 
multiple fractions for high total dose; usually 
10–20 fractions to allow normal tissue 
recovery with goal of minimizing risk of late 
permanent radiation side effects.
• Stereotactic radiation therapy is newer 
technique that allows more conformal 
treatment than conventional techniques to 
avoid toxicity to normal tissue without 
sacrificing tumor control; comparable dose 
delivered over much shorter time than with 
conventional techniques; stereotactic radio  ­ 
therapy involves 1–5 consecutive daily 
fractions.
• Palliative radiation involves much lower 
total dose than definitive to minimize toxicity 
while improving quality of life through 
reduction of tumor size; usually 4–6 fractions.
• Combining radiation therapy with novel 
drug therapy (toceranib phosphate—Palladia®, 
and others) appears safe and well tolerated.
• Radiation therapy followed by surgery to 
debulk residual mass may improve local 
control time, but results in higher rate of 
• Surgery alone considered ineffective, with 
most tumors relapsing within 6 months.
• During radiation therapy, supportive care 
for radiation ­related mucositis may involve 
softening food; rinsing mouth with “magic 
mouthwash” (topical anesthetic), saline, or 
dilute black tea; and administration of 
medications to control discomfort.
• These side effects temporary, but may cause 
discomfort for 10–14 days.
ACTIVITY
• Limit activity to minimize risk of epistaxis 
and dyspnea.
• Using harness instead of collar during walks 
may help minimize epistaxis.
DIET
• Soften food if needed during radiation therapy.

Canine and Feline, Seventh Edition  33
A
• Avoid extremes of temperatures and salty 
foods with radiation therapy–related 
mucositis.
• Nasal adenocarcinoma may be painful 
even though pet not showing visible signs 
of pain.
• Consider use of medications for discomfort, 
epistaxis, and congestion.
• Radiation therapy most effective option 
and well tolerated using modern radiotherapy 
techniques, with fewer side effects than 
previously reported.
• Radiation side effects may impact patient’s 
quality of life during treatment, but most pets 
enjoy relatively normal quality of life following 
• Intermittent congestion, nasal discharge, 
and sneezing may occur post therapy due to 
increased sensitivity from tumor’s destruction 
of nasal turbinates.
Anesthetic recovery—ensure airway is 
maintained until animal is sternal and alert, 
to prevent apnea in patients with bilateral 
nasal obstruction.
• Chemotherapy is considered ineffective for 
durable tumor control, but may benefit some 
patients if radiation therapy is not viable 
option. Various drugs have been described, 
including cisplatin (dogs only), carboplatin, 
doxorubicin, and piroxicam. Toceranib 
phosphate (Palladia) exerts therapeutic 
activity against nasal carcinoma.
• Consult with oncologist for more details.
• Adequate analgesic therapy should be 
employed as needed in patients suffering from 
invasive disease with bone destruction, signs 
of pain, or radiation therapy side effects.
Cisplatin—never use in cats.
• Most chemotherapeutics have risk of 
gastrointestinal, hematologic, and other 
potential side effects, and should be 
administered and monitored by an 
oncologist.
• Piroxicam can cause gastric ulceration, so 
careful monitoring of appetite, vomiting, and 
stool color (melena) is recommended.
Concurrent radiation therapy and chemo­
therapy will increase risk of side effects, but 
have not shown to significantly improve 
tumor control.ALTERNATIVE DRUG(S)
• Palladia, a tyrosine kinase inhibitor, may 
have anticancer activity in some carcinomas, 
including nasal adenocarcinomas. It is 
currently being investigated alone and in 
combination with radiation therapy.
• Objective responses have been documented 
with use of Palladia alone.
• Yunnan Baiyao, a Chinese herbal medication, 
is often prescribed for epistaxis.
  FOLLOW-UP
• Clinical response is usually observed within 
2–3 weeks from start of radiation therapy. 
Reductions in epistaxis, nasal discharge, 
congestion, and sneezing are expected.
• CT or MRI is needed to assess objective 
tumor response to therapy and is recommended 
2–3 months post radiation treatment.
• Other staging tests, including thoracic 
imaging (radiography or CT) and lymph 
node evaluation, are generally recommended 
at 3­month intervals during/following 
therapy.
• Routine staging with CT/MRI and 
monitoring of recurrent clinical signs can 
detect early recurrence.
• Pain.
• Dyspnea.
• Epistaxis.
• Secondary infections.
• Weight loss.
• Anorexia.
• Chemotherapy or radiation toxicity.
• Untreated—median survival around 2–6 
months.
• Definitive conventional and stereotactic 
radiation therapy—median survival times 
reported at 12–18 months in dogs and 12–20 
months in cats; 1 ­year survival rate 20–57% 
(dogs and cats); 2 ­year survival rate 20–48% 
(dogs and cats).
• Presence of cribriform lysis, brain involve­
ment, or metastatic disease (advanced stage) 
are poor prognostic indicators.
• Ophthalmic complications of radiation 
therapy—more likely in dogs than cats.
• Incidence and severity of ophthalmic 
toxicity have dramatically decreased with 
advanced radiation therapy techniques now 
commonly used.
• Chronic rhinitis is possible following 
radiation therapy for sinonasal tumors and 
may require periodic symptomatic therapy.  MISCELLANEOUS
Chemotherapeutic drugs and general 
anesthesia are a risk to the fetus and would 
not be recommended in pregnant animals.
SYNONYMS
• Nasal carcinoma.
• Nasal tumor.
SEE ALSO
• Chondrosarcoma, Nasal and Paranasal Sinus.
• Squamous Cell Carcinoma, Nasal and 
Paranasal Sinus.
• Squamous Cell Carcinoma, Nasal Planum.
• COX ­2 = cyclooxygenase ­2.
• https://veterinarymedicine.dvm360.com/
vetmed/Medicine/Canine ­and­feline ­
nasaltumors/ArticleStandard/Article/
detail/735167
• https://www.ncbi.nlm.nih.gov/pubmed?ter
m=dog+nasal+carcinoma+radiotherapy&cmd
=DetailsSearch
Adams WA, Bjorling DE, McAnulty JF , et al. 
Outcome of accelerated radiotherapy alone 
or accelerated radiotherapy followed by 
exenteration of the nasal cavity in dogs with 
intranasal neoplasia: 53 cases (1990–2002). 
J Am Vet Med Assoc 2005, 227:936–941.
Adams WA, Kleiter MM, Thrall DE, et al. 
Prognostic significance of tumor histology 
and computed tomographic staging for 
radiation treatment response of canine nasal 
tumors. Vet Radiol Ultrasound 2009, 
50(3):330–335.
Geiger TL, Nolan MW. Linac ­based 
stereotactic radiation therapy for canine 
non­lymphomatous nasal tumors: 29 cases 
(2013–2016). Vet Comp Oncol 2018, 
16:E68–E75.
Henry CJ, Brewer WG, Tyler JW, et al. 
Survival in dogs with nasal adenocarcinoma: 
64 cases (1981–1995). J Vet Intern Med 
1998, 12:436–439.
LaDue TA, Dodge R, Page RL, et al. Factors 
influencing survival after radiotherapy of 
nasal tumors in 130 dogs. Vet Radiol 
Ultrasound 1999, 40:312–317.
Author  Jayme S. Looper
Consulting Editor  Timothy M. Fan(continued)  Adenocarcinoma, Nasal

34 Blackwell’s Five-Minute Veterinary Consult  
A
  BASICS
OVERVIEW
• Malignant tumor of ductal or acinar origin 
arising from the exocrine pancreas.
• Usually metastatic by the time of diagnosis, 
affecting regional lymph nodes and visceral 
abdominal organs (liver) and associated 
peritoneal cavity.
• Rare in dogs—0.5–1.8% of all tumors.
• Rare in cats—2.8% of all tumors.
• Older female dogs and Airedale terriers at 
higher risk than others.
• Median age (dogs)—9.2 years.
• Mean age (cats)—11.6 years.
SIGNS
• Nonspecific—fever; vomiting; weakness; 
anorexia; icterus; malabsorption syndrome; 
weight loss.
• Abdominal pain—variable.
• Abdominal effusion—malignant.
• Metastasis to bone and soft tissue common.
• Pathologic fractures secondary to metastasis 
reported.
• Palpable abdominal mass (cats).
• Paraneoplastic syndromes of epidermal 
necrosis, hyperinsulinemia, and hypergluca-
gonemia may be present.
• Average duration of clinical signs (cats): 41 
days, range 2–180 days.
Unknown
  DIAGNOSIS
• Primary pancreatitis; may be concurrent 
and complicate or delay early diagnosis.
• Pancreatic pseudocyst.
• Pancreatic nodular hyperplasia.
• Hepatic neoplasia.
• Other causes of vomiting and icterus.
• Peritoneal carcinomatosis.
• Other causes of abdominal effusion in cats.
• Usually nonspecific changes (e.g., mild 
anemia and neutrophilia).
• Hyperamylasemia less reliable than 
hyperlipasemia.
• Lipase concentrations are often markedly 
elevated and may serve as a noninvasive 
biochemical marker of neoplasia in dogs.
Rarely there may be significant metabolic 
alterations that affect glucagon, insulin, and 
amino acid concentrations.IMAGING
• Abdominal radiographs may reveal a mass 
or loss of serosal detail associated with 
concurrent pancreatitis or peritoneal effusion.
• Ultrasonography may reveal one or more 
masses or concurrent pancreatitis (mixed 
echogenicity, large pancreas, hyperechoic 
peripancreatic fat). Pancreatic thickening, 
abdominal effusion, and single to multiple 
nodules of varying size may be identified. 
Sonographic findings may be impossible to 
distinguish from pancreatic nodular hyper  - 
plasia. Rarely the ultrasound of the pancreas 
may appear normal except for dilation of the 
pancreatic duct.
• Abdominal CT will allow for therapeutic 
decisions regarding surgical resectability and 
approach, which can affect the owner’s 
willingness to treat.
• Surgical biopsy—definitive.
• Fine-needle aspirate cytology—supportive. 
In many cases, where the tumor is not 
resectable, the fine-needle aspirates may 
provide strong enough evidence to start 
medical treatment.
  TREATMENT
• None reported curative.
• Palliation of pain with aggressive analgesic 
combinations is necessary.
• Surgical intervention to alleviate intestinal 
and biliary obstruction, if necessary.
• Surgery is typically not a good option in 
many cases, due to the extent of the disease at 
the time of diagnosis.
• If surgery is an option, partial or total 
pancreatectomy may prolong survival. A 
Whipple procedure (pancreaticoduodenectomy) 
and/or partial colon resection may be required 
for tumor resection. This can influence the 
perisurgical morbidity and mortality risk.
• T reat concurrent pancreatitis.
• Antiemetics and supportive care (hydration 
and caloric requirements).
• Gemcitabine is used in humans for the 
treatment of pancreatic carcinoma, and while 
used in dogs with cancer, it has not been 
established as the standard of care for dogs 
with pancreatic adenocarcinoma.
• Always consult a veterinary oncologist for 
updates in treating this rare neoplasm.
N/A  FOLLOW-UP
• Intestinal obstruction
• Biliary obstruction
• Pancreatic abscess
• Peritonitis
• Metastasis
EXPECTED COURSE AND 
PROGNOSIS
Progression to death is often rapid given that 
there is no successful curative treatment 
available. Despite the grave prognosis, 
individual patients treated with complete 
resection of their tumor and chemotherapy, in 
the absence of systemic metastasis, may have 
prolonged survival.
Gastrin-secreting pancreatic carcinoma 
(gastrinoma) has been reported in dogs and 
cats. Clinical signs are associated with 
hypergastrinemia, which results in inapprop -
riate hydrochloric acid secretion by the 
stomach, leading to gastroduodenitis.
Cave T, Evans H, Hargreavest J, et al. 
Metabolic epidermal necrosis in a dog 
associated with pancreatic adenocarcinoma, 
hyperglucagonaemia, hyperinsulinaemia, 
and hypoaminoacidaemia. J Small Anim 
Pract 2007, 48:522–526.
Hecht S, Penninck DG, Keating JH. Imaging 
findings in pancreatic neoplasia and nodular 
hyperplasia in 19 cats. Vet Radiol Ultrasound 
2006, 48:45–50.
Linderman MJ, Brodsky EM, de Lorimier LP , 
et al. Feline exocrine pancreatic carcinoma: 
a retrospective study of 34 cases. Vet Comp 
Oncol 2013, 11(3):208–218.
Author  Nick Dervisis
Consulting Editor  Timothy M. FanAdenocarcinoma, Pancreas

Canine and Feline, Seventh Edition  35
A Adenocarcinoma, Prostate
  BASICS
OVERVIEW
• Prostatic adenocarcinoma (PAC) is a 
malignant tumor that occurs in both neutered 
and intact male dogs.
• Although this neoplasm represents <1% of 
all canine malignancies, it is the most common 
prostatic disorder in neutered male dogs.
• Metastases to regional lymph nodes, lungs, 
and the lumbosacral skeleton are common.
• Dogs and rarely cats.
• Medium- to large-breed intact or neutered 
male dogs.
• Median age of 9–10 years.
SIGNS
• Tenesmus (with the production of 
ribbon-like stool).
• Stranguria and dysuria.
• Rear limb lameness.
• Lethargy.
• Exercise intolerance.
• A firm, asymmetric, and immobile prostate 
gland.
• Prostatomegaly is common, but is not 
always present.
• Pain may be elicited in response to 
abdominal or rectal palpation.
• Caudal abdominal mass, cachexia, pyrexia, 
and dyspnea may also be identified.
Neutered males are at increased risk for 
prostatic neoplasia.
  DIAGNOSIS
• Other primary neoplasia (i.e., squamous 
cell carcinoma, transitional cell carcinoma).
• Metastatic or locally invasive neoplasia (i.e., 
transitional cell carcinoma).
• Acute or chronic prostatitis, benign prostatic 
hypertrophy, and prostatic cysts are possible 
differentials in intact male dogs, but are 
highly unlikely in neutered dogs.
• Inflammatory leukogram possible.
• Alkaline phosphatase may be high.
• Postrenal azotemia may be present if 
urethral obstruction exists.
• It is prudent to evaluate urine samples via 
cystocentesis and free-catch techniques, as 
hematuria, pyuria, and malignant epithelial cells 
may be observed in free-catch samples, but are 
unusual in samples obtained by cystocentesis.OTHER LABORATORY TESTS
Serum and seminal plasma markers such as 
acid phosphatase, prostate-specific antigen, 
and canine prostate-specific esterase are not 
elevated in dogs with PAC.
IMAGING
• Thoracic radiography—metastases may 
appear as pulmonary nodules or increased 
interstitial markings.
• Abdominal radiography—sublumbar 
lymphadenomegaly, mineralization of the 
prostate, and lytic lesions to the lumbar 
vertebrae or pelvis may be seen.
• Abdominal ultrasonography—focal to 
multifocal hyperechogenicity with asymmetry 
and irregular prostatic outline, ± prostatic 
mineralization.
• Contrast cystography may help differentiate 
prostatic from urinary bladder disease.
• Prostatic aspirate (percutaneous or trans- 
rectal).
• Prostatic wash.
• Prostatic biopsy performed percutaneously 
or surgically.
• Percutaneous biopsy has been associated 
with tumor seeding along the biopsy tract.
  TREATMENT
• Prostatectomy if local disease (success of 
this procedure depends on skill of surgeon 
and extent of disease).
• Radiation therapy may palliate signs and 
prolong survival.
• Neutering—however, most tumors are not 
androgen responsive.
• Stenting of the prostatic urethra will resolve 
urinary outflow obstruction and thereby 
• Chemotherapy—carboplatin, cisplatin, or 
doxorubicin; may offer short-term benefit.
• Pain relief with nonsteroidal anti-inflamma-
tory drugs (NSAIDs), morphine-derived drugs.
• Stool softeners to relieve tenesmus.
N/A
  FOLLOW-UP
Ability to urinate and defecate, pain secondary 
to skeletal metastases, quality of life.PREVENTION/AVOIDANCE
Keeping dogs sexually intact may decrease risk.
• Urethral obstruction.
• Metastasis to regional lymph nodes, skeleton, 
and lungs.
Guarded to poor, survival of 2–6 months 
depending upon presenting clinical 
symptoms.
None
N/A
drug.
• PAC = prostatic adenocarcinoma.
Axiak SM, Bigio A. Canine prostatic 
carcinoma. Compend Contin Educ Vet 
2012, 34(10):E1–E4.
Author  Ruthanne Chun

36 Blackwell’s Five-Minute Veterinary Consult  
AAdenocarcinoma, Renal
  BASICS
OVERVIEW
• Accounts for <1% of all reported neoplasms 
in dogs.
• Renal tumors tend to be highly metastatic, 
locally invasive, and often bilateral.
• Renal cystadenocarcinoma, a rare heritable 
syndrome with a less aggressive behavior and 
better long-term prognosis than renal adeno  - 
carcinoma, has been described in German 
shepherd dogs.
• Adenocarcinoma—older (8–9 years) dogs, 
1.6 : 1 male-to-female ratio, no breed 
• Cystadenocarcinoma—German shepherd 
dogs, often female.
SIGNS
• Adenocarcinoma—insidious, nonspecific 
signs such as weight loss, inappetance, 
lethargy, hematuria, and pale mucous 
membranes.
• Cystadenocarcinoma—may present for 
nodular dermatofibrosis, a syndrome of 
painless, firm, fibrous lesions of the skin and 
subcutaneous tissues.
• Adenocarcinoma—unknown.
• Cystadenocarcinoma—heritable in German 
  DIAGNOSIS
• Other primary neoplasia (i.e., lymphoma, 
nephroblastoma).
• Metastatic neoplasia (i.e., hemangiosarcoma).
• Renal adenoma or cyst.
• CBC may show paraneoplastic poly-
cythemia or leukocytosis, or anemia.
• Biochemistry may be normal, or may reveal 
azotemia. Marked gamma-glutamyltransferase 
(GGT) elevation may be prognostic.
• Urinalysis may show hematuria, proteinu-
ria, bacteriuria, or casts.
Urine culture and sensitivity.
IMAGING
• Thoracic radiographs—metastatic disease 
reported in up to 16% of patients.
• Abdominal radiographs—mass visualized in 
81% of patients.
• Abdominal ultrasonography, CT, or 
contrast radiography—useful in identifying 
and staging the disease.DIAGNOSTIC PROCEDURES
• Renal biopsy (ultrasound guided or 
surgical) for definitive diagnosis.
• Mitotic index found to be prognostic in 70 
dogs treated with nephrectomy.
  TREATMENT
• Aggressive surgical excision is the treatment 
of choice for unilateral disease.
• Successful chemotherapeutic management 
of either disease has not been described.
• Supportive management for patients in 
renal failure may be necessary.
None
N/A
  FOLLOW-UP
• Renal failure—measure serum urea 
nitrogen and creatinine; urinalysis.
• Quality of life if bilateral or otherwise 
nonsurgical disease.
N/A
• Renal failure.
• Metastatic disease.
• Invasion of local vital structures (vena cava, 
aorta).
• Adenocarcinoma—median reported 
survival of 49 dogs was 16 months (range 
0–59).
• Cystadenocarcinoma—few large studies of 
this rare disease, reported median survival of 
12+ months with no definitive therapy.
• Based on mitotic index: >30 mitotic 
figures/10 high-power fields (hpf; median 
survival of 187 days) vs. 10–30/10 hpf 
(median survival of 452 days) vs. <10/hpf 
(median survival of 1184 days).
• The paraneoplastic syndromes of hyper-
trophic osteopathy, polycythemia, and a neutrophilic leukocytosis have been reported 
in isolated cases.
• Nodular dermatofibrosis and uterine 
leiomyomas are commonly associated with 
cystadenocarcinoma.
• GGT = gamma-glutamyltransferase.
• hpf = high-power field.
Bryan JN, Henry CJ, T urnquist SE, et al. 
Primary renal neoplasia of dogs. J Vet Intern 
Med 2006, 20:1155–1160.
De Lorimier LP , Bernard S. Marked serum 
GGT elevations in two dogs with renal 
carcinoma. Letter to the Editor. J Small 
Anim Pract 2017, 58:187.
Edmondson EF , Hess AM, Powers BE. 
Prognostic significance of histologic features 
in canine renal cell carcinomas: 70 
nephrectomies. Vet Pathol 2015, 52:260–268.
Knapp DW. T umors of the urinary system. 
In: Withrow SJ, Vail DM, eds., Small 
Animal Clinical Oncology, 4th ed. 
Philadelphia, PA: Saunders, 2007, pp. 
649–658.

Canine and Feline, Seventh Edition  37
A
  BASICS
OVERVIEW
• T umor arising from major (e.g., parotid, 
mandibular, sublingual, or zygomatic) or 
minor salivary glands.
• Mandibular or parotid glands constitute 
80% of cases.
• Mandibular gland most frequently affected 
in dogs.
• Parotid gland most frequently affected in 
cats.
• Cats typically have more advanced disease 
than dogs at time of diagnosis.
• Metastasis—regional lymph node in 39% 
of cats and 17% of dogs at diagnosis; distant 
metastasis reported in 16% of cats and 8% of 
dogs at diagnosis, but may be slow to develop.
• Epithelial malignancies—constitute roughly 
85% of salivary gland tumors.
• Adenomas comprise only 5% of salivary 
tumors.
• Mean age, 10–12 years.
• Siamese cats may be at relatively higher risk.
• Male cats affected twice as often as female cats.
• No other breed or sex predilection has been 
determined.
SIGNS
• Unilateral, firm, painless swelling of the 
upper neck (mandibular and sublingual), ear 
base (parotid), upper lip or maxilla (zygo-
matic), or mucous membrane of lip (acces-
sory or minor salivary tissue).
• Other signs may include halitosis, weight 
loss, anorexia, dysphagia, exophthalmus, 
Horner’s syndrome, sneezing, and dysphonia.
Unknown
  DIAGNOSIS
• Mucocele.
• Abscess.
• Soft tissue sarcoma, e.g., fibrosarcoma.
Results often normal.
N/A
IMAGING
• Regional radiographs usually are normal; 
may see periosteal reaction on adjacent bones 
or displacement of surrounding structures.• MRI or CT imaging allows superior 
discrimination of tumor for surgery and/or 
radiation treatment planning.
• Thoracic radiographs indicated to check for 
lung metastases.
• Cytologic examination of aspirate may 
differentiate salivary adenocarcinoma from 
mucocele and abscess.
• Biopsy for histopathology is required for 
  TREATMENT
• Aggressive surgical resection—when 
possible; most are invasive and difficult to 
excise completely.
• Radiotherapy—good local control and 
prolonged survival may be possible.
• Aggressive local resection (usually histologi-
cally incomplete) followed by adjuvant 
radiation can achieve local control and 
long-term survival in some cases, but further 
studies are needed to determine the most 
effective treatment, including the possible 
role for chemotherapy.
Chemotherapy efficacy is largely unreported; 
however, it may be indicated for treatment/
palliation of metastatic disease.
N/A
  FOLLOW-UP
Evaluations—physical examination and 
thoracic radiographs every 3 months 
reasonable if aggressive surgery and/or 
radiation therapy employed.
Temporary acute side effects (e.g., moist 
dermatitis and alopecia) expected with 
radiation therapy. Consultation with a 
radiation oncologist is recommended 
regarding specific, anatomic site–related side 
effects associated with planned dose and field 
size.
• Improved survival time in dogs without 
evidence of nodal or distant metastasis at 
diagnosis; clinical stage not prognostic 
for cats.• Median survival 550 days for dogs and 516 
days for cats in retrospective study.
• Local control obtained through radiation 
and/or surgery is critical to outcome.
Hammer A, Getzy D, Ogilvie G, et al. 
Salivary gland neoplasia in the dog and cat: 
survival times and prognostic factors. 
JAAHA 2001, 37:478–482.
Blackwood L, Harper A, Elliot J, Gramar I. 
External beam radiotherapy for the 
treatment of feline salivary gland carcinoma: 
six new cases and a review of the literature. J 
Feline Med Surg 2019, 21(2):186–194.
Author  Anthony J. Mutsaers
Consulting Editor  Timothy M. FanAdenocarcinoma, Salivary Gland

38 Blackwell’s Five-Minute Veterinary Consult  
A
  BASICS
OVERVIEW
• Malignant growth originating from 
sebaceous or apocrine sweat glands of the skin.
• Approximately 2% of all skin tumors in 
dogs.
• Apocrine sweat gland—rare in dogs, 
uncommon in cats.
• Sebaceous gland—rare in both dogs and 
cats.
• Middle-aged to older pets.
• Male intact dogs overrepresented for 
sebaceous gland adenocarcinomas.
• Female dogs overrepresented for apocrine 
adenocarcinoma in one study.
SIGNS
• May appear as solid, firm, raised, superficial 
skin lesions.
• May be ulcerated and bleeding and 
accompanied by inflammation of the 
surrounding tissue.
• Apocrine sweat gland—often poorly 
circumscribed, ulcerated and potentially 
purple in color; very invasive into underlying 
tissue; may occur anywhere on the body, 
frequently affecting the limbs and trunk in 
dogs and head, limbs, and abdomen in cats.
• Sebaceous gland—often nodular, ulcerated 
and inflamed, moderate risk of lymph node 
involvement; frequently found on head and 
neck in dogs and on the head, thorax, and 
perineum in cats.
• Dermal and lymphatic tracking can be 
observed early in disease course.
Unknown
  DIAGNOSIS
• Other more frequent skin tumors.
• Cutaneous histiocytic diseases.
• Immune-mediated skin diseases.
• Deep bacterial/fungal infections.
Normal
N/A
IMAGING
Thoracic radiographs recommended at time 
of diagnosis to assess for distant metastases.
• Biopsy for histopathology and definitive 
• Cytologic examination or biopsy of 
draining lymph nodes.PATHOLOGIC FINDINGS
• Apocrine gland adenocarcinomas are 
divided into multiple subtypes based on the 
anatomic location they arise in. They typically 
are invasive into the underlying stroma and 
blood vessels, and often show poorly 
demarcated borders and a high mitotic index.
• Sebaceous gland adenocarcinomas often 
reveal lymphatic vessel invasion.
  TREATMENT
• Aggressive en bloc  surgical excision, 
including resection of draining lymph node, 
recommended for both types. 
Histopathologic analysis of lymph nodes 
assists with determining prognosis and 
establishing adjuvant treatment plan.
• Margins of entire tissue specimen must be 
evaluated histologically to assess completeness 
of resection.
• Radiation therapy may be recommended 
for treatment of draining lymph nodes after 
resection to prevent recurrence and develop-
ment of regional metastasis; radiation therapy 
of primary tumor site recommended when 
wide and complete resection not possible.
• Chemotherapy has been used anecdotally 
for the treatment of both tumor types, in 
both species.
• Contact a veterinary oncologist for any 
updated treatments that may be available.
• Nonsteroidal anti-inflammatory drugs and 
other analgesics are recommended, as 
indicated, for pain control.
None
  FOLLOW-UP
• Sebaceous gland adenocarcinoma—little is 
known about the metastatic potential of this 
malignancy, but it may be rapidly metastatic 
to regional lymph nodes in some patients; 
long-term prognosis is anecdotally good with 
multimodal therapy combining aggressive 
surgery, chemotherapy, and radiation therapy.
• Apocrine gland adenocarcinoma—fair to 
good long-term prognosis; the histologic 
finding of vascular invasion is a negative 
prognostic factor predicting systemic 
metastases; aggressive surgical resection (local 
and regional tumor control) followed by 
adjuvant chemotherapy is recommended to improve survival. A study reported a 
postexcisional median survival time of 
30 months in dogs.
Carpenter JL, Andrews LK, Holzworth J. 
T umors and tumor like lesions. In: 
Holzworth J, ed. Diseases of the Cat: 
Medicine and Surgery. Philadelphia, PA: 
Saunders, 1987, pp. 406–596.
Hauck ML. T umors of the skin and subcuta-
neous tissues. In: Withrow SJ, Vail DM, 
Page RL, eds., Small Animal Clinical 
Oncology, 5th ed. St. Louis, MO: Elsevier 
Saunders, 2013, pp. 305–320.
Haziroglu R, Haligur M, Keles H. 
Histopathological and immunohistochemi-
cal studies of apocrine sweat gland 
adenocarcinomas in cats. Vet Comp Oncol 
2014, 12(1):85–90.
Kycko A, Jasik A, Bocian L, et al. 
Epidemiological and histopathological 
analysis of 40 apocrine sweat gland 
carcinomas in dogs: a retrospective study. J 
Vet Res 2016, 61:331–337.
Pakhrin B, Kang MS, Bae IH, et al. 
Retrospective study of canine cutaneous 
tumors in Korea. J Vet Sci 2007, 
8:229–236.
Simko E, Wilcock BP , Yager JA. A retrospec-
tive study of 44 canine apocrine sweat gland 
adenocarcinomas. Can Vet J 2003, 
44(1):38–42.
Author  Jason Pieper
Louis-Philippe de Lorimier.Adenocarcinoma, Skin (Sweat Gland, Sebaceous)

Canine and Feline, Seventh Edition  39
A
  BASICS
OVERVIEW
• Uncommon tumor arising from the 
epithelial lining of the gastrointestinal tract.
• Prognosis guarded to poor.
• Dog more commonly affected than cat.
• Middle-aged to older ( >6 years) animals; 
age range 3–13 years.
• No breed predisposition.
• Possible male predisposition.
SIGNS
• Stomach—vomiting, anorexia, weight loss, 
hematemesis, and melena.
• Small intestine—vomiting, weight loss, 
borborygmus, flatulence, and melena.
• Large intestine and rectum—mucus, 
blood-tinged feces, and tenesmus.
• Stomach—nonspecific, melena on rectal 
exam.
• Small intestine—may feel mid-abdominal 
mass; distended, painful loops of small bowel.
• Large intestine and rectum—palpable mass 
per rectum, may form annular ring, may have 
multiple nodular lesions protruding into the 
colon; bright red blood on rectal exam.
• Unknown.
• Possible genetic cause—gastric adenocarci-
nomas in related Belgian shepherds and 
Dutch Tervuren shepherds.
  DIAGNOSIS
• Inflammatory bowel disease.
• Parasites.
• Leiomyoma.
• Leiomyosarcoma.
• Pancreatitis.
• Stomach and small intestine—may see 
microcytic, hypochromic, nonregenerative 
anemia (iron-deficiency anemia). Mild and 
persistent elevations in blood urea nitrogen in 
the face of normal creatinine can support GI 
protein or blood loss.
• Large intestine and rectum—no characteristic 
changes.
Fecal occult blood may be positive; diet 
affects results—can recheck to confirm after 
3 days of non-meat diet.IMAGING
• Ultrasound—may reveal a thickened 
stomach or bowel wall; may see mass in the 
gastrointestinal tract, enlarged lymph nodes.
• Positive contrast radiography—filling defect 
(stomach); intraluminal space-occupying or 
annular constriction (small bowel); gastric 
neoplasm most often found in distal two- 
thirds of stomach.
• Double contrast radiography—large 
intestine and rectum; polypoid or annular 
space-occupying masses.
• Advanced imaging with contrast CT can 
provide highest-quality images of gastrointes-
tinal tract and assessment for presence and 
extent of lymphadenopathy.
• Ultrasound-guided fine-needle aspirate of 
bowel mass or enlarged lymph node may 
provide definitive cytologic diagnosis.
• Endoscopic biopsy may be nondiagnostic 
because tumors are frequently deep to the 
mucosal surface; thus surgical biopsy often 
required.
• Presence of signet ring cells and/or 
cytoplasmic microvacuolation on cytologic 
evaluation of gastric biopsy squash prep 
samples correlated well with diagnosis of 
gastric adenocarcinoma in one study.
  TREATMENT
• Surgical resection—treatment of choice; 
seldom curative.
• Gastric—usually nonresectable.
• Small intestine—remove by resection and 
anastomosis; metastasis to regional lymph 
nodes and liver common.
• Large intestine and rectal—may occasionally 
be resected via pull-through surgical procedure; 
metastasis common; transcolonic debulking 
may provide palliation of obstruction.
• Chemotherapy—only anecdotal reports, 
usually unsuccessful.
• Piroxicam 0.3 mg/kg PO q24h can provide 
palliation for large intestinal and rectal tumors.
Seek advice before initiating treatment with 
cytotoxic drugs.
  FOLLOW-UP
Physical examination, thoracic radiographs, 
and abdominal ultrasound—at 1, 3, 6, 9, and 
12 months post surgery.EXPECTED COURSE AND PROGNOSIS
Dogs
• Overall poor; pedunculated rectal tumors 
do best; most cases recur locally, develop 
metastasis, or do both rapidly.
• Median survival gastric—2 months.
• Median survival small intestinal—10 
months.
• Mean survival large intestinal—annular 
1.6 months vs. pedunculated 32 months.
Cats
• Guarded.
• Few reported cases, but may have 
 prolonged survival ( >1 year).
Crawshaw J, Berg J, Sardinas JC, et al. 
Prognosis for dogs with nonlymphomatous 
small intestinal tumors treated by surgical 
excision. J Am Anim Hosp Assoc 1998, 
34:451–456.
Riondato F , Miniscalco B, Berio E, et al. 
Diagnosis of canine gastric adenocarcinoma 
using squash preparation cytology. Vet J 
2014, 201(3):390–394.
Seim-Wikse T, Jorundsson E, Nodtvedt A, 
et al. Breed predisposition to canine gastric 
carcinoma: a study based on the Norwegian 
canine cancer register. Acta Vet Scand 2013, 
55:25.
Swann HM, Holt DE. Canine gastric 
adenocarcinoma and leiomyosarcoma: a 
retrospective study of 21 cases (1986–1999) 
and literature review. J Am Anim Hosp 
Assoc 2002, 38:157–164.
von Babo V, Eberle N, Mischke R, et al. 
Canine non-hematopoietic gastric 
neoplasia: epidemiologic and diagnostic 
characteristics in 38 dogs with post-surgical 
outcome of five cases. Tierarztl Prax Ausg K 
Kleintiere Heimtiere 2012, 40(4):243–249.
Consulting Editor  Timothy M. FanAdenocarcinoma, Stomach, Small and Large Intestine, Rectal

40 Blackwell’s Five-Minute Veterinary Consult  
AAdenocarcinoma, Thyroid—Dogs
  BASICS
A malignant tumor arising from the follicular 
or parafollicular cells (medullary/C-cells) of 
the thyroid gland.
• About 60% of patients are euthyroid, 30% 
hypothyroid, and 10% hyperthyroid.  
• Typically very invasive tumors with high 
rate of metastasis (lungs, retropharyngeal 
lymph nodes, liver), with up to 35–40% of 
dogs having metastasis at time of diagnosis. 
• Animals with bilateral tumors have a 16 
times greater risk of developing metastatic 
disease than animal with unilateral tumors.
• Cardiovascular—hyperthyroid dogs are 
usually tachycardic and may have systemic 
hypertension. • Endocrine/metabolic—affected 
dogs may be hypothyroid, euthyroid, or 
hyperthyroid; hypercalcemia may be seen as a 
paraneoplastic syndrome or secondary to 
concurrent parathyroid hyperplasia or para  - 
thyroid adenocarcinoma. • Respiratory—dogs 
may be dyspneic owing to a space-occupying 
mass adjacent to the trachea; metastasis to the 
lungs common. Large compressive masses can 
result in caval syndrome manifested as facial 
edema. Compression and/or deviation of the 
trachea can lead to nonproductive cough.
GENETICS
Unknown
Accounts for 1.2–3.8% of all canine tumors 
and represents 10–15% of all primary head 
and neck tumors.
May be more common in iodine-deficient 
areas.
Species
Dog
Boxers, golden retrievers, Siberian huskies, 
and beagles at increased risk, but seen in any 
breed.
Older dogs (median 9–15 years; range 4–18 
years).
No sex predilection.
SIGNS
• Usually not diagnosed until a large mass is 
palpable.  • Approximately 65% are unilateral, 
35% are bilateral.Historical Findings
• Palpable mass/swelling in cervical neck, 
coughing, dyspnea, dysphagia, dysphonia, 
facial edema, neck pain. • If functional 
thyroid tumor—may see polyuria, polydipsia, 
polyphagia, weight loss, restless behavior, 
diarrhea (symptoms associated with hyperthy-
roidism). • If hypothyroid—may see poor 
hair coat, weight gain, lethargy.
• Freely movable or fixed cervical mass, 
unilateral or bilateral. • Rarely may see 
Horner’s syndrome, or cranial vena cava 
syndrome. • If hyperthyroid—cardiac 
arrhythmias or murmurs.
CAUSES
Unknown
• Breed predilection.
• Iodine deficiency.
  DIAGNOSIS
• Other primary neoplasms—lymphoma; 
soft tissue sarcoma; salivary gland adeno -
carcinoma; parathyroid carcinoma; carotid 
body tumor. • Secondary tumors—metastatic 
oral/tonsillar squamous cell carcinoma; oral 
melanoma. • Inflammatory—abscess or 
granuloma. • Salivary mucocele.
• Usually normal. • May see nonregenerative 
normocytic normochromic anemia of chronic 
disease, leukocytosis. • Rare—hypercalcemia; 
isosthenuria.
Thyroid hormone (T4 and/or free T4 levels) 
and endogenous thyroid-stimulating 
hormone (TSH) levels.
IMAGING
• Thoracic radiography (three-view)—
evaluation of lungs and other thoracic 
structures for metastasis. • Cervical 
ultrasonography, CT, and MRI—evaluation 
of tissue of origin, vascularity, invasion, and 
cervical lymph nodes. • Technetium-99m 
scintigraphy to evaluate for ectopic and 
functional thyroid tissue or metastatic 
lesions. • Radioiodine studies—may provide 
information about the tumor’s ability to 
produce thyroid hormone.
Biopsy
T ru-Cut® not recommended owing to 
high risk of severe hemorrhage; open 
biopsy usually required and allows for 
controlled hemostasis in the event of 
bleeding.Cytology
• Examination of fine-needle aspirates from 
tumor and palpable regional lymph nodes.
• Specimen almost always heavily 
contaminated with blood owing to highly 
vascular nature of tumor. • Homogeneous 
population of epithelial cells, sometimes 
with colloid and/or tyrosine-containing 
granules. Often, cell fragility leads to cell 
rupture and free nuclei. • Unable to 
differentiate malignant from benign thyroid 
cells; but almost all thyroid neoplasms in 
dogs are malignant.
Gross
• Characterized by high vascularity with areas 
of hemorrhage and necrosis. • Usually poorly 
encapsulated; often invade adjacent tissues 
(e.g., trachea and esophagus, and surrounding 
vasculature); may adhere to jugular vein, 
carotid artery, and vagosympathetic trunk.
• Thyroid follicular carcinomas are 
subclassified as well differentiated (follicular, 
compact, follicular–compact, or papillary), 
poorly differentiated, or undifferentiated—
with follicular–compact and compact tumors 
most common in dogs. • C-cell (e.g., 
parafollicular, medullary) carcinomas less 
common. May need special stains to 
differentiate between C-cell and follicular 
carcinomas.
  TREATMENT
• Definitive treatment dependent on tumor 
stage (tumor size, mobility, and evidence of 
metastatic disease). • Complete surgical 
excision recommended for freely movable 
thyroid tumors. • Full course external beam 
radiation therapy recommended preopera-
tively for large tumors, as sole therapy for 
nonresectable tumors, or postoperatively for 
incompletely surgically removed tumors. 
• Palliative radiation and/or chemotherapy 
recommended for tumors that are metastatic 
at presentation. • Functional thyroid 
carcinomas can be treated with iodine-131, 
but doses are very large (60–100 mCi) and 
therefore there are limited facilities that offer 
this therapy. • Toceranib phosphate (Palladia®) 
can exert cytoreductive activity. • Isotretinoin 
9-cis postoperatively may improve median 
survival time (MST) in follicular–compact 
and compact thyroid carcinoma.
Varies with signs on examination.
ACTIVITY
Restrict activity if dyspneic.

Canine and Feline, Seventh Edition  41
A
• Warn owners of importance of controlling 
heart rate and rhythm in hyperthyroid 
patients and of possibility of episodes of 
collapse. • Warn owners of possible postop-
erative laryngeal paralysis and intraoperative 
hemorrhage. • Warn owners of acute 
radiation therapy toxicities—moist desqua-
mation, laryngitis, tracheitis, esophagitis.
See Appropriate Health Care.
Risks
• Marked hemorrhage—tumors highly 
vascular and invasive into surrounding 
structures, including vasculature; may need 
blood transfusion and intensive postoperative 
care. • Laryngeal paralysis—owing to trauma 
to recurrent laryngeal nerve. • Damaged 
parathyroid glands—may occur during 
surgery.
• Chemotherapeutic agents: ◦ Chemotherapy 
recommended as sole therapy, or possibly in 
combination with surgery and/or radiation 
therapy. ◦ Cisplatin (60 mg/m2 every 3 
weeks), carboplatin (300 mg/m2 every 3 
weeks), or doxorubicin (30 mg/m2 every 3 
weeks)—reported to effect partial remission 
in approximately 50% of cases. ◦ Toceranib 
(2.5–3 mg/kg 3 times a week)—had biologic 
activity in 80% of cases (26% partial 
remission, 53% stable disease). ◦ Isotretinoin 
9-cis (2 mg/kg/day)—potentially difficult to 
obtain in United States due to prescribing 
restrictions. • Thyroid management: 
◦ Thyroxine—maintenance doses to decrease 
TSH production have been recommended; 
some tumors contain TSH receptors; value of 
hormone replacement therapy in affected 
dogs not determined. ◦ Methimazole 5 mg 
PO q8h for medium to large dogs; may be 
beneficial for hyperthyroid patients. ◦ Beta 
blockers—may be indicated for tachycardia or 
hypertension in hyperthyroid patients.
• Doxorubicin is cumulatively toxic to 
cardiac myocytes, causing decreased 
myocardial function; do not give to animals 
with poor cardiac function or dilated cardio  - 
myopathy. • Cisplatin is nephrotoxic; do not 
give to animals with renal disease.PRECAUTIONS
Chemotherapy can cause gastrointestinal, 
bone marrow, cardiac, and other toxicities—
seek advice from medical oncologist if 
unfamiliar with cytotoxic drugs.
Verapamil—may potentiate doxorubicin-
induced cardiotoxicity.
N/A
  FOLLOW-UP
• Serum calcium concentration—if bilateral 
thyroidectomy was performed; signs of 
hypocalcemia (agitation, panting, muscle 
tremors, tetany, and seizures) may be 
observed. ◦ T reat with 10% calcium 
gluconate (1–1.5 mL/kg IV over 10–20 
minutes). ◦ Maintain serum calcium with 
dihydrotachysterol (vitamin D) orally and/or 
oral calcium supplementation if necessary. 
• Thyroid hormone—supplementation with 
thyroxine may be necessary after bilateral 
thyroidectomy. • TSH concentration—a goal 
of thyroxin supplementation is to down -
regulate the body’s secretion of TSH. • Site of 
primary tumor—physical exam  ination and 
cervical ultrasound; thoracic radiographs 
every 3 months to detect pulmonary 
metastasis.
Unknown
• T umor—anemia; thrombocytopenia; 
hypercalcemia; respiratory distress. 
• Chemotherapy—dilated cardiomyopathy; 
renal failure; pancreatitis; sepsis; gastro -
intestinal upset. • Surgery—hemorrhage; 
hypothyroidism; hypoparathyroidism leading 
to hypocalcemia; laryngeal paralysis. 
• Radiotherapy—acute side effects: moist 
desquamation, pharyngeal mucositis, 
esophagitis, tracheitis; late side effects: 
hypothyroidism, alopecia, and skin or coat 
color change (at radiation site).
• Prognosis—related to grade and stage of 
disease (tumor size, mobility, and evidence of 
metastatic disease) with small, low-grade, 
nonattached unilateral, nonmetastatic tumors 
having best prognosis. • MST after surgical removal of unilateral thyroid tumors is 1,462 
days vs. 365 days for patients undergoing 
bilateral thyroidectomy. • For animals treated 
with full course external beam radiation 
therapy—progression-free survival at 1 year 
80% and 72% at 3 years in one study, and in 
another study MST 24.5 months. • Palliative 
radiation therapy in 13 dogs—MST 24 
months vs. 170 days in dogs with advanced 
disease. • 131I therapy in combination with 
surgery—MST 34 months, or 131I alone MST 
30 months. • Animals treated with cisplatin 
alone (13 dogs)—overall response rate 53%, 
median progression-free interval for 
responders 202 days, and overall MST 
98 days.
• Nonthyroidal malignancies common.
• Multiple endocrine neoplasia reported.
None
It is not recommended to breed animals with 
cancer. Chemotherapy is teratogenic—do not 
give to pregnant animals.
SYNONYMS
Thyroid carcinoma.
• MST = median survival time.
• TSH = thyroid stimulating hormone.
Lunn KF , Page RL. T umors of the endocrine 
system. In: Withrow SJ, Vail DM, Page RL, 
eds., Small Animal Clinical Oncology, 
5th ed. Philadelphia, PA: Saunders, 2013, 
pp. 513–515.
Nadeau ME, Kitchell BE. Evaluation of the 
use of chemotherapy and other prognostic 
variables for surgically excised canine 
thyroid carcinoma with and without 
metastasis. Can Vet J 2011, 
52(9):994–998.
Pack L, Roberts RE, Davson SD, Dookwah 
HD. Definitive radiation therapy for 
infiltrative thyroid carcinoma in dogs. Vet 
Radiol Ultrasound 2001, 42:471–474.
Author  Rebecca G. Newman
Consulting Editor  Timothy M. Fan(continued)  Adenocarcinoma, Thyroid—Dogs

42 Blackwell’s Five-Minute Veterinary Consult  
A
  BASICS
OVERVIEW
• Aggression toward other dog(s) within a 
household or with dogs that are familiar and 
spend time together regularly. • Dogs can form 
stable social relationships quickly, sometimes 
within minutes of being introduced. Aggression 
usually revolves around resources (e.g., food, 
toys, owner attention, resting places), but may 
be fear related or can occur at times of 
excitement/arousal (e.g., visitors or other dogs 
on the property). • Usually within the range of 
normal behavior, but may be excessive, 
abnormal, or related to underlying medical 
conditions.
Behavioral
Approximately 11%.
• No breed or sex predilection. • Although 
genetic factors contribute, environment may play 
a stronger role in degree of aggression exhibited.
Signs usually develop at social maturity 
(approximately 18–36 months of age).
May be more common/intense between intact 
males and females.
SIGNS
• Barking, growling, lip‐lifting, snarling, 
snapping, lunging, biting, directed toward 
other dogs in the home. • Subtle commun­
ication signals between dogs may include 
blocking access to rooms or other resources, 
hard stare, taller stance, tail elevated, ears 
perked forward, and approaching/direct 
contact with other dog. • May be accompanied 
by fearful/submissive body postures/facial 
expressions (e.g., crouching, backing away, 
ears back, tail tucked, looking away, lip‐
licking). • Dogs fighting in a household may 
get along well except in specific trigger 
situations, especially resources, access to 
passageways/doorways, and at times of 
arousal. • Predictors of aggression—presence 
of owner; access to resources such as food, 
toys, spaces, and beds; periods of high arousal 
such as people entering the house.
• Underlying medical conditions including 
pain, endocrinopathies, neurologic, and sensory 
decline. • May be normal canine behavior; can 
be strongly influenced by previous experience 
(e.g., early socialization, previous aggressive 
encounters with other dogs, inappropriate 
punishment) and other behavioral disorders 
such as anxiety; in some cases, one dog may not read or respond appropriately to other dog’s 
body language. • Aggression likely to be more 
severe between dogs of equal size, age, and sex. 
• Owner’s inability to read early signs of 
conflict between household dogs. • Owner’s 
failure to create or maintain social stability and 
predictability in dogs’ interactions and relation ­ 
ship with each other.
  DIAGNOSIS
• Status‐related aggression. • Conflict‐related 
aggression. • Play behavior/nonaggressive 
arousal. • Possessive aggression. • Protective 
aggression. • Fear aggression. • Pain‐related 
aggression. • Irritable aggression. • Generalized 
anxiety disorder.
To rule out underlying medical conditions 
and as baseline prior to drug use.
As needed to rule out underlying medical 
conditions; thyroid screening.
IMAGING
conditions, (e.g., pain); MRI if CNS disease 
suspected.
N/A
  TREATMENT
• T reatment requires a multifaceted approach, 
including immediate management to ensure 
safety and prevent recurrence, behavior 
modification, and medication (if indicated). 
• Successful treatment requires owner 
understanding of canine social behavior and 
communication, identification of all aggression‐
eliciting stimuli, risks involved in living with an 
aggressive dog(s), willingness and ability to 
follow safety and management recommen­
dations, and effective implementation of 
reward‐based behavior modification. • Realistic 
expectation is for managing triggers, most often 
for rest of dog’s life and gradually improving, 
not resolving. • Owners must be aware that the 
only way to entirely prevent future injuries may 
be to continually separate dogs when no one is 
home, remove one of the dogs from the home, 
or use of safety equipment and constant 
supervision to safely manage when dogs are in 
same space. • Positive punishment and 
dominance‐based training can lead to increased 
aggression, fear, and injuries, and must be 
avoided.Safety Recommendations
• Never  allow dogs to “fight it out,” as serious 
injuries may occur. • Owners must ensure 
safety by identifying and avoiding all situations 
that may trigger aggressive interactions, such as 
when dogs are walking past each other in a 
confined space or being given attention or 
high‐valued treats; the dogs may at least initially 
need to be kept physically separated to prevent 
agonistic encounters. • Owners must be 
instructed in methods of safely breaking up 
fights by never reaching toward the dogs’ heads 
or necks to physically pull them apart; preferred 
methods include physical barrier deterrent 
(e.g., noise distractor, water, or deterrent spray) 
or leashes left constantly attached when dogs 
are together. • Owners should be advised of 
their liability for bites. • For treatment to be 
effective, aggression‐provoking stimuli should 
be prevented prior to behavior modification. 
• At any time or place an aggression‐evoking 
situation could arise (e.g., around food/valued 
resources), dogs must be confined away from 
each other or under direct physical control of a 
responsible adult; dogs can be separated by 
placing in separate rooms, with pet gates, 
exercise pens, or crates, or securely tethered 
short term to hooks installed in walls. • Tools 
for safety and management include head 
halters, basket muzzles, or harnesses with 
leashes attached for prevention, and to safely 
remove dogs from situations that may elicit 
aggression. • If safety cannot be ensured, it may 
be necessary to rehome dog to a single‐dog 
household, where all triggers can be avoided.
Behavior Therapy
• Structured interaction programs (such as 
“Learn to earn” or “Say please by sitting”), 
where dog is taught to consistently perform a 
desired behavior (e.g., sit) before receiving 
anything it values (e.g., attention, food), give 
the dog control of its resources by being calm, 
provide structure and predictability in all 
interactions, teach impulse control, and train 
dog using positive interactions (e.g., good 
things happen by sitting calmly). • Separately, 
teach each dog behaviors that will serve as a 
foundation for management and control when 
together including sit and relax, down‐settle, 
go to mat or crate, focus on owner (e.g., 
watch/look), and leave it; private sessions with 
force‐free trainer can be the best option for 
achieving success. • Once each dog can reliably 
perform foundation and relaxation exercises, 
then owners can work with dogs together, 
separated by distance to ensure both dogs can 
remain focused or engaged in desirable 
behaviors (e.g., mat) that can be reinforced. 
• During times together, close supervision is 
needed; owners must be able to recognize body 
language and be vigilant for stimuli that might 
incite aggression; verbal cues should be used to 
prevent or interrupt undesirable behaviors and 
teach what is desirable; use of a leash attached

teach what is desirable; use of a leash attached 
to each dog with head halter or while wearing Aggression—Between Dogs in the Household

Canine and Feline, Seventh Edition  43
A
basket muzzle will increase safety when dogs 
are in close proximity. • Use positive reinforce­
ment (e.g., treats, toys, petting) to teach 
behaviors incompatible with those that lead to 
aggression (e.g., response substitution, 
differential reinforcement of alternative 
behavior). • Systematic desensitization and 
counter‐conditioning to triggers—desensiti­
zation is a process by which dogs will be 
exposed to their triggers under their threshold; 
food, toys, verbal praise, or physical attention 
(e.g., petting) can be used to reward calm 
behavior. Counter‐conditioning is a process in 
which positive associations are paired with 
each stimulus exposure, (e.g., most‐valued 
treats); dogs should be exposed to each other 
under control of handlers and at distance at 
which they can remain calm and focused on 
their handlers while performing cued behaviors 
for rewards; gradually dogs can be moved 
closer in proximity to each other and in varied 
situations while focusing on handlers.
Castration reduced intermale aggression in 
62% of dogs.
• No medications licensed for treatment of 
canine aggression; owners must have 
informed consent of potential side effects and 
risks, and that use is off‐label. • Owners need 
to understand that medication will not ensure 
safety and to follow all safety procedures. 
• Medications may be indicated for moderate 
to intense fear and anxiety, impulsivity, and 
reactivity. • Proper diagnosis with behavioral 
modification plan, including appropriate 
selection of behavioral drugs, leads to most 
successful outcomes.
Selective Serotonin Reuptake Inhibitors 
(SSRIs)
• Fluoxetine 0.5–2 mg/kg PO q24h. 
• Paroxetine 0.5–1 mg/kg PO q24h.
• Sertraline 1–3 mg/kg PO q24h. • Side 
effects—sedation, irritability, gastrointestinal 
tract (GIT) effects, agitation; decreased appetite 
common and usually transient.
Tricyclic Antidepressants (TCAs)
• Clomipramine 1–3 mg/kg q12h (label‐
restricted for aggression). • Side effects—
sedation, GIT effects, anticholinergic effects, 
cardiac conduction disturbances if 
predisposed, agitation.For Situational or Adjunctive Use
Alpha‐2 Agonists
• Clonidine 0.01–0.05 mg/kg PO PRN 
1.5–2 hours before eliciting trigger, up to 
q8–12h. • Side effects—transient hyper­
glycemia, anticholinergic, hypotension, 
collapse, bradycardia, and agitation.
Serotonin 2a Antagonist/Reuptake Inhibitors
• T razodone 2–5 mg/kg PO PRN prior to 
eliciting trigger, up to q8h—may titrate up to 
8–10 mg/kg if no adverse effects; use cautiously 
at higher doses and when combining with other 
drugs that increase serotonin due to risk of 
serotonin syndrome. • Side effects—sedation, 
anorexia, ataxia, GIT effects, cardiac conduction 
disturbances, agitation.
Benzodiazepines
• Might be used to reduce anxiety prior to 
eliciting trigger. • Side effects—sedation, 
lethargy, ataxia, paradoxical excitement; may 
disinhibit aggression.
Corticosteroids may cause or contribute to 
polyphagia, increased food guarding, and 
irritability.
Use caution, as any psychotropic medication 
may cause undesirable changes in behavior, 
including increased irritability and aggression.
Do not combine SSRIs, TCAs, or monoamine 
oxidase (MAO) inhibitors (e.g., amitraz, 
selegiline) and use cautiously or avoid with 
opioids, tramadol, or other medications that 
increase serotonin—can result in serotonin 
syndrome.
Natural products—dog‐appeasing pheromones, 
supplements containing alpha‐casozepine or 
l‐theanine, or a calming probiotic might be 
considered for mild to moderate anxiety or 
used adjunctively.
  FOLLOW‐UP
• Clients will need ongoing assistance and 
should receive at least one follow‐up within 
first 1–3 weeks after consultation. Provisions 
for further follow‐up should be made at that 
time. • Drugs should only be prescribed 
under direct supervision and monitoring of 
veterinarian.PREVENTION/AVOIDANCE
Safety and management recommendations are 
lifelong.
Injuries to dogs and humans.
• Lifelong management likely necessary.
• Prognosis for improvement depends on 
severity of aggression; motivation; whether 
triggers can be identified, avoided, and safely 
managed; and owner compliance; prognosis 
more favorable if triggers are predictable and 
preventable, and aggression occurs at low 
intensity. • Aggression may recur with change in 
routine, housing, or health, and increasing age.
Other fear‐ or anxiety‐related conditions; 
possessive, redirected, and territorial aggression.
Human injury/bite wounds.
Do not breed dogs that exhibit aggressive 
behavior.
SEE ALSO
• Aggression, Food and Resource Guarding—  
Dogs.
• Aggression, Overview—Dogs.
• Fears, Phobias, and Anxieties—Dogs.
• GIT = gastrointestinal tract.
• MAO = monoamine oxidase.
• SSRI = selective serotonin reuptake inhibitor.
Herron ME, Shofer SS, Reisner IR. Survey of the 
use and outcome of confrontational and non‐
confrontational training methods in client‐
owned dogs showing undesired behaviors. Appl 
Anim Behav Sci 2009, 117:47–54.
Landsberg G, Hunthausen W, Ackerman L. 
Behavior Problems of the Dog and Cat, 
3rd ed. St. Louis, MO: Saunders Elsevier, 
2013, pp. 320–324.
Pike A. Managing canine aggression in the 
home. Vet Clin N Am Small Anim Pract 
2018, 48:387–402.
Authors  Jeannine Berger and Wailani Sung
Consulting Editor  Gary M. Landsberg
Acknowledgment  The authors and editors 
acknowledge the prior contributions of 
Meredith E. Stepita and Laurie Bergman.(continued)  Aggression—Between Dogs in the Household

44 Blackwell’s Five-Minute Veterinary Consult  
AAggression to Unfamiliar People and Unfamiliar Dogs—Dogs
  BASICS
OVERVIEW
• Aggression directed toward person or dog 
that does not live in the household. • Variety 
of motivations including fear, territoriality, 
conflict, and possessiveness. • Usually within 
range of normal behavior, but may be excessive 
or abnormal due to learning, early experiences, 
genetics, or underlying medical conditions.
Stranger‐directed aggression represents 32.5% 
of canine behavioral referral caseload. May be 
skewed as many cases may go unreported.
None
• Any age. • Signs may begin to emerge as 
primary socialization wanes (12–16 weeks of 
age) or may arise or intensify at social 
maturity (18–36 months). • Genetic 
concerns and more guarded prognosis when 
signs arise before 12 weeks.
• May be overrepresented in males. 
• Territorial aggression more common in 
intact males—initial signs usually present by 
1 year.
SIGNS
other dogs or people. • Subtle communication 
signals may include blocking access to 
resources, hard stare, taller stance, tail elevated, 
ears perked forward, and approaching or 
direct contact. • May be accompanied by 
fearful/submissive body postures/facial 
expressions (e.g., crouching, backing away, ears 
back, tail tucked, looking away, lip‐licking). 
• Territorial aggression arises in familiar 
locations or spaces (e.g., home, yard, car) with 
confident body language. • Fear aggression 
more likely when dog is cornered or cannot 
escape. • May be more frequent or severe on‐ 
than off‐leash, on own property, or when 
behind barrier (e.g., fence, pet gate, crate).
• Underlying medical conditions, including 
pain, endocrinopathies, neurologic, sensory 
decline. • May be normal canine behavior. 
Strongly influenced by previous experience, 
(e.g., socialization, unpleasant outcomes/
associations) such as previous fear‐evoking or 
aggressive encounters with dogs or people, 
punishment, and other behavior disorders 
including fear, anxiety, and reactivity. • May 
begin as unruly or exuberant behavior or during leash (walk) training. Owner responses 
including leash corrections, verbal and/or 
physical punishment may increase fear, 
anxiety, and arousal, and condition further 
negative associations. • Owner’s inability to 
read early signs of fear or conflict. • Owner’s 
failure to create or maintain predictable 
pattern of positive interactions with unfamiliar 
people and dogs. • Fear of strangers.
  DIAGNOSIS
• Fear aggression. • Territorial aggression. 
• Possessive aggression. • Protective 
aggression. • Conflict‐related aggression. 
• Generalized anxiety disorder. • Pain‐related 
aggression. • Irritable aggression.
and as baseline prior to any drug use.
conditions, including thyroid screening.
IMAGING
  TREATMENT
• T reatment requires a multifaceted approach 
including management to ensure safety and 
prevent recurrence, behavior modification, 
and medication. • T reatment must focus on 
managing the problem and gradually modifying 
behavior to reduce fear, anxiety, and aggres ­
sion, not cure/full resolution. • Successful 
treatment requires owner understanding of 
canine social behavior and communication, 
risks, identification of all aggression‐eliciting 
stimuli, how to implement safe management, 
and effective implementation of reward‐based 
behavior modification. • Owners must be 
aware that the only certain way to prevent 
future injuries is avoidance of stimuli. 
• Educate owners that use of physical or 
verbal punishment, confrontation, or 
establishing dominance (such as alpha rolls), 
and corrections with choke chains or prong 
collars, can lead to human injury, further 
negative associations with stimuli, increased 
fear, anxiety, and aggression, and disruption of 
human–animal bond.
Safety Recommendations
• Preventing or avoiding stimuli/triggers that 
evoke fear, anxiety, or aggression is essential to ensure safety, prevent further repetition and 
potential intensification of the problem, 
address pet welfare, and provide an environ­
ment in which pet can learn and desired 
outcomes can be achieved, prior to 
implementing behavior modification. 
• Decrease or avoid visitors and unfamiliar 
dogs to the home. • Avoid walks at times or in 
locations where stimulus exposure might occur. 
On walks, maintain a 15 ft distance from other 
people and dogs. • Confine dog away from 
potential targets; stay below threshold, (e.g., 
distance, location); and ensure direct physical 
control of adult together with safety products if 
any possible exposure. • Confine territorial 
dogs to where they cannot see/hear visitors 
approaching territory before they become 
alerted or aggressive. Confine dogs for duration 
of visitor’s stay inside house. • Safety measures 
include training dogs to wear a basket muzzle, 
use of head collars or harnesses with leashes 
attached, and confinement training (e.g., safe 
haven, closed doors, barricades) away from 
potential triggers. • Owners should be advised 
of their liability for bites. • Ensure that dog 
cannot escape through fencing or unlatched 
gates or doors. • If safety cannot be ensured, 
dog should be removed from household.
where dog is taught to consistently perform 
desired behavior (e.g., to sit) before receiving 
anything it values (e.g., attention, petting, 
feeding, going for a walk), give dog control of 
its resources for being calm, provide structure 
and predictability in all interactions, teach 
impulse control, and train dog using positive 
interactions (e.g., good things happen by 
sitting calmly). • Use positive reinforcement 
to train alternative desirable behaviors (e.g., 
response substitution) that can be used during 
stimulus exposure. • T rain each behavior in 
neutral situations with most motivating 
rewards (e.g., treats, food, toys, petting) to 
achieve outcomes immediately and success­
fully in absence of stimuli, including a calm 
sit; go to bed or crate to settle; walk on loose 
leash; focus on owner for guidance using eye 
contact (e.g., watch, look); find it (e.g., move 
away for a reward); and hand target (e.g., 
touch nose to owner’s hand). • Private 
sessions with force‐free trainer are often 
recommended to achieve foundation basics 
before any exposure. • Behavior modification—
desensitization (DS) is process by which dogs 
will be exposed to their triggers under their 
threshold and rewarded if remain calm. 
Counter‐conditioning (CC) is process in 
which trigger or stimulus is paired with 
positive outcomes with each exposure. 
• When owner can effectively keep dog calm 
and under control, and get desirable outcomes 
on cue in absence of stimuli, begin exposure 
by determining limit (e.g., distance, location,

Canine and Feline, Seventh Edition  45
A
person, dog) at which dog will orient but not 
yet react. Pair highest‐value rewards with each 
exposure. • Gradually (baby steps) increase 
stimulus intensity, staying below threshold 
that will result in fear and/or aggression by 
decreasing distance, increasing distractions, or 
moving to more challenging environments. 
• Progress is slow (typically weeks to months). 
Carefully monitor body language to avoid 
setbacks. • Owners must always be vigilant 
for approach of stimuli that might incite fear 
or aggression. • Discuss whether referral to 
veterinary behavior specialist is recommended 
for counseling on risk assessment, prognosis, 
behavioral management, behavior modific­
ation, and medication use.
Castration reduced aggression by at least 50% 
toward unfamiliar dogs in <20% of dogs and 
toward human territorial intruders in <10% 
of dogs. Castration reduced intermale 
aggression in 62% of dogs.
canine aggression. Owners must have 
informed consent of risks, potential side 
effects, and that medication use is off‐label. 
to intense fear, anxiety, impulsivity, and 
reactivity. • Ensure that owners understand 
risks of owning aggressive dog, that medication 
will not ensure safety, and that they follow 
safety procedures. • Proper diagnosis with 
behavioral modification plan, including 
appropriate selection of behavioral drugs, 
leads to most successful outcome.
For Ongoing Use
Selective Serotonin Reuptake Inhibitors
• Paroxetine 0.5–1 mg/kg PO q24h. 
tract (GIT) effects, agitation; decreased 
appetite common and usually transient.
Tricyclic Antidepressants
cardiac conduction disturbances if predis­
posed, and increased agitation.
For Situational or Adjunctive Use
1.5–2 hours before eliciting trigger, up to q8–12h. • Side effects—transient hyperglyce­
mia, anticholinergic, hypotension, bradycar­
dia, and agitation.
Serotonin 2a Antagonist/Reuptake 
Inhibitors
8–10 mg/kg if no adverse effects. Use 
cautiously at higher doses and when combin ­
ing with other drugs that increase serotonin 
due to risk of serotonin syndrome. • Side 
effects—sedation, anorexia, ataxia, GIT effects, 
cardiac conduction disturbances, agitation.
• May be used to reduce anxiety prior to 
lethargy, ataxia, paradoxical excitement, may 
Corticosteroids can be contraindicated in food‐
aggressive dogs; could cause or contribute to 
polyphagia, resource guarding, and irritability.
Use caution—any psychotropic medication 
including increased irritability or aggression.
Do not combine selective serotonin reuptake 
inhibitors (SSRIs), tricyclic antidepressants 
(TCAs), and monoamine oxidase (MAO) 
inhibitors (e.g., amitraz, selegiline) and use 
cautiously or avoid with opioids, tramadol, 
and other medications that increase seroto­
nin—can result in serotonin syndrome.
Natural products—dog‐appeasing 
pheromones, supplements containing  
alpha‐casozepine or l‐theanine, or a calming 
probiotic might be considered for mild to 
moderate anxiety or used adjunctively.
  FOLLOW‐UP
• Clients will need ongoing assistance with at 
least one follow‐up within the first 1–3 weeks 
after consultation. Provisions for further 
follow‐up should be made at that time. 
• Drugs should only be prescribed under the 
supervision and monitoring of a veterinarian.
Safety and management recommendations 
are lifelong.
Injuries to dogs and humans.EXPECTED COURSE AND PROGNOSIS
• Resolution may not be achievable and 
lifelong management may be necessary. 
• Prognosis based on whether triggers can be 
avoided to ensure safety and prevent recurrence, 
and whether improvement can be achieved 
with behavior modification and medication. 
• Prognosis more favorable if aggression occurs 
at low intensity and in predictable situations. 
• Prognosis dependent on owner compliance. 
• Approximately 75% of dogs aggressive 
toward unfamiliar dogs could be around other 
dogs on leash after treatment.
Human/dog injury and bite wounds.
behavior.
SEE ALSO
Dogs.
• Fear and Aggression in Veterinary Visits— 
Dogs.
Herron ME, Shofer SS, Reisner IR. Survey of 
the use and outcome of confrontational and 
non‐confrontational training methods in 
client‐owned dogs showing undesired 
behaviors. Appl Anim Behav Sci 2009, 
177:47–54.
Horwitz D, ed. Blackwell’s 5 Minute Consult 
Clinical Companion: Canine and Feline 
Behavior, 2nd ed. Hoboken, NJ: Wiley‐
Blackwell, 2018, pp. 58–69, 89–99.
Behavior Problems of the Dog and Cat, 3rd 
ed. St. Louis, MO: Saunders Elsevier, 2013, 
pp. 320–324.
Meredith E. Stepita and Laurie Bergman.(continued)  Aggression to Unfamiliar People and Unfamiliar Dogs—Dogs

46 Blackwell’s Five-Minute Veterinary Consult  
AAggression Toward Children—Dogs
  BASICS
OVERVIEW
Children are the most frequently reported 
victims of dog bites and tend to be injured 
more severely than adults.
Dogs of any breed, age, sex, and neuter status.
Breed
• Breeds vary with demographics. Breed 
identification may be unreliable. • Breeds 
most commonly presenting to a behavior 
referral service that had bitten a child 
include English springer spaniel, German 
shepherd, Labrador retriever, Golden 
retriever, and American cocker spaniel. 
• Most fatal attacks (rare) are attributed to 
Rottweilers, pit bulls, and their mixes. 
• Larger dogs may be more likely to inflict 
severe injury. • Smaller breeds can also be 
dangerous and may invite inappropriate 
handling by children.
Sex
• More frequent in males than females. 
• Unneutered males are overrepresented in 
severe bites. • Neutering will not significantly 
reduce the risk.
Age
• Any age, but more frequent at or beyond 
social maturity (2+ years). • Risk may 
increase in geriatric dogs because of pain, 
sensory impairment, or cognitive decline.
SIGNS
Aggression
Clinical Categories/Motivation
• Fear related. • Pain related. • Play related. 
• Conflict related. • Predatory behavior.
• Territorial. • Resource guarding.
Dog‐Associated Risk Factors
• Disease and associated irritability. 
• Pain‐related aggression and resource 
guarding are the most common reasons for 
bites to familiar children <6 years old. 
• Anxiety. • Fear. • Dog lying down, 
particularly under or on furniture. • Parent/
littermate aggression. • History of growling, 
snapping, biting.
Environmental/Social Risk Factors
• Younger children most likely bitten by the 
family pet or other familiar dogs. • Presence 
of infants (risk of predatory attacks). 
• Presence of young children. • Presence of 
food, edible toys. • Punishment‐based 
training triggering defensiveness. • Inadequate 
supervision by parents/caregivers. • Hugging, 
kissing, or bending over anxious, fearful, 
conflict‐aggressive, or resource‐guarding dogs.  DIAGNOSIS
See Causes & Risk Factors.
To rule out medical contributing factors.
Anecdotal evidence correlates hypothyroidism 
with increased aggression; however, no data‐
based evidence exists.
IMAGING
N/A
• Detailed history of the bite event and the 
behavior of both dog and child to determine 
motivation or trigger. • Pain assessment.
  TREATMENT
SAFETY WITH FAMILIAR DOGS
• Never leave infants or young children 
unsupervised with dogs. Securely separate infants 
from dogs when alone, even if both asleep. • If 
one adult is present, separate dog from young 
children. • If more than one adult is present, 
assign responsibility for one adult to dog, and one 
to child. • Educate owners to read and recognize 
canine communication signals and triggers. • Do 
not allow child to approach or interact with dog 
when dog is lying down or in possession of 
resources. • Separate dog when eating or chewing 
valued items. • Do not allow child to hug, kiss, 
bend over, or lie down beside dog.
SAFETY WITH UNFAMILIAR DOGS
• Do not tether unsupervised. • Do not allow 
young children to interact with unfamiliar 
dogs. • Securely lock gates in yards. • Avoid 
underground electric fences that do not prevent 
entry of children into yard or escape of dogs.
BEHAVIOR MODIFICATION
• Establish secure, separate “safe haven” for dog. 
• Restrict fearful or reactive dog on lead and 
offer food at safe distance from children, to turn 
a negative situation into a positive one. • Do not 
rely on training alone; safety requires prevention. 
• Redirect dog’s attention: teach “look” or 
“touch” cues. • Consider positive conditioning 
to basket muzzle; however, supervised inter­
actions are still essential, as muzzles do not 
insure safety. • Avoid punishment, which may 
increase anxiety and aggression. 
May be indicated for dogs with generalized 
or situational anxiety or fearful behavior.Selective Serotonin Reuptake 
Inhibitors (SSRIs)
• Fluoxetine 0.5–2.0 mg/kg q24h. 
• Sertraline 0.5–4 mg/kg q24h or divided 
q12h. • Paroxetine 0.5–1.5 mg/kg q24h.
• Clomipramine 1–3 mg/kg q12h.
Natural products containing alpha‐  
casozepine, l‐theanine, calming probiotic,  
or a dog‐appeasing pheromone may aid in 
reducing anxiety.
• Psychotropic medication can increase 
agitation and anxiety or disinhibit aggression. 
Use with safety recommendations to prevent 
bites. • Avoid SSRI or TCA in combination. 
◦ Use cautiously or avoid with any drugs that 
increase serotonin. ◦ Avoid use of SSRI or 
TCA + monoamine oxidase inhibitor (MAOI), 
including amitraz.
  FOLLOW‐UP
• Do not rely on training alone to eliminate 
aggression. • Preventive measures are most 
important in management of aggression to 
children. • Even well‐trained, socialized dogs 
may bite.
• Family may not recognize or acknowledge 
risks. • Disease may aggravate aggression. 
• Family may not be compliant. • Psychotropic 
drug may be unrealistically relied upon or 
ineffective. • Access of young children to dog 
may be difficult to control.
• Aggressive behavior can often be reduced 
and controlled, but not “cured.” Lifetime 
compliance is needed. • Prognosis is poor if 
social/physical environment cannot be 
controlled. • In some cases it may be necessary 
to rehome or euthanize dog, while in some 
dogs behavior may improve as child grows older.
• MAOI = monoamine oxidase inhibitor. 
inhibitor. • TCA = tricyclic antidepressant.
Reisner IR, Shofer FS, Nance ML. Behavioral 
assessment of child‐directed canine aggression. 
Inj Prev 2007, 13:348–351.
Author  Ilana R. Reisner

Canine and Feline, Seventh Edition  47
A Aggression Toward Familiar People—Dogs
  BASICS
OVERVIEW
• Aggression directed toward household 
members or people with an established 
relationship with the dog, often in situations 
when they are handling or attempting to 
interact with the dog, or involving access to 
certain resources. • Variety of motivations 
including fear, protective, conflict, and 
possessiveness. • Usually within range of 
• Approximately 7%. • Represents 20–44% 
of behavioral referral caseloads may be skewed 
as many cases unreported. • Bites from larger 
dogs may require medical attention, therefore 
more likely documented.
• Behavior is a result of interplay between 
ontogeny and phylogeny. • Environmental 
stimuli may play a more critical role in 
aggression. • May be increased occurrence in 
related dogs. • May be genetic factors 
associated with impulse dyscontrol in English 
springer spaniel and English cocker spaniel; 
more common in conformation lineage than 
field lineage in English springer spaniels. • In 
other breeds, dogs bred for show may be 
associated with less aggression.
• Usually manifested by social maturity 
(12–36 months of age). • Genetic concerns 
and poorer prognosis if signs arise before 
12 weeks.
May be overrepresented in males (castrated 
and intact).
SIGNS
familiar people. • Subtle communication 
• May be more frequent when handled or 
approached when resting, avoiding, or hiding 
(e.g., under furniture) or grabbing (e.g., 
collar). • Protective or possessive aggression 
arises in vicinity of highly valued objects/space 
or people. • Fear aggression can be defensive or offensive and more likely to occur when 
cornered or cannot escape.
pain, endocrinopathies, neurologic, and 
sensory decline. • May be normal canine 
behavior; can be strongly influenced by 
previous experience (e.g., socialization, early 
development, unpleasant outcomes including 
previous aggressive encounters, punishment), 
and other behavioral disorders such as fear, 
anxiety, and impulsivity. • Owner’s inability 
to read early signs of fear or conflict. 
• Owner’s failure to create or maintain 
predictable pattern of positive interactions.
  DIAGNOSIS
• Fear/defensive aggression. • Territorial 
aggression. • Possessive aggression. 
• Protective aggression. • Conflict‐related 
aggression. • Generalized anxiety disorder. 
• Pain‐related aggression. • Irritable 
aggression.
IMAGING
conditions (e.g., pain); MRI if CNS disease 
N/A
  TREATMENT
• T reatment requires multifaceted approach, 
modification, and medication (where 
indicated). • Realistic expectation is for 
managing triggers, most often for rest of dog’s 
life, and gradually improving, not resolving, 
the problem. • Successful treatment requires 
owner understanding of canine social 
behavior and communication, identification 
of all aggression‐eliciting stimuli, willingness 
and ability to follow safety and management 
recommendations, and effective implemen­
tation of reward‐based behavior modification. 
establishing dominance such as with alpha rolls, and corrections with choke chains or 
prong collars, can lead to human injury, 
further negative associations with the stimuli, 
increased fear, anxiety and aggression, and 
disruption of human–animal bond.
• Owners must ensure safety by identifying and 
avoiding situations that may evoke fearful or 
aggressive response; identification and avoidance 
of triggers is essential to ensure safety, for pet 
welfare, and to provide environment in which 
pet can learn and desired outcomes be achieved, 
prior to implementing behavior modification. 
• Safety measures include training to wear a 
basket muzzle, use of head collars or harnesses 
with leashes attached, and use of confinement 
training and barriers (e.g., safe haven, gates, 
closed doors) to keep dog from triggers and 
triggers from dog. • Owners should be advised 
of their liability for bites. • T reatment more 
likely to be successful if aggression‐provoking 
stimuli can be effectively prevented prior to 
behavior modification. • Common triggers 
include handling or moving dog when on 
furniture or resting, use of physical punishment, 
touching painful areas, and removing valued 
items; this can be managed by keeping dog 
away from areas/furniture, when using physical 
punishment, using pain control and taking dog 
to veterinarian for uncomfortable procedures, 
and not to give (or confine when giving) valued 
items. • If safety cannot be ensured, dogs should 
be removed from household and euthanasia 
considered if prognosis poor for safe rehoming.
“Learn to earn” or “Say please by sitting”) 
where dog is consistently taught to perform a 
feeding, toys) give dog control of its resources 
for being calm, provide structure and predict­
ability in all interactions, teach impulse control, 
and train dog using positive interactions (e.g., 
good things happen by sitting calmly). • Use 
positive reinforcement to teach alternative 
desirable behaviors that are incompatible (e.g., 
response substitution) with those that have 
resulted in aggression. • Teach each behavior 
in neutral situations using most motivating 
rewards (e.g., food, toys, play, attention), 
including sit and relax on verbal cue; down‐
settle; go to bed or crate; focus on owner (e.g., 
watch/look), and hand targeting (e.g., touch 
nose to owner’s hand). Private sessions with 
force‐free trainer often recommended to 
achieve foundation basics before any exposure. 
• Behavior modification—desensitization is 
process by which dogs are exposed to triggers 
under their threshold; rewards should be given 
when calm (e.g., food, toys, verbal praise, or 
physical attention); counter‐conditioning is 
process in which positive associations paired 
with exposure to stimulus, (e.g., most valued

48 Blackwell’s Five-Minute Veterinary Consult  
A
treats); operant counter‐conditioning or 
response substitution is process in which 
acceptable alternative behaviors that are 
incompatible with undesirable behavior are 
reinforced. • Reinforce your dog for being 
calm as family members approach or beyond 
threshold distance when in a location or in 
possession of an item that might trigger 
aggression; always use nonconfrontational 
techniques; start handling in nonpainful/
sensitive areas. • Start by staying below 
threshold that would result in fear and/or 
aggression, then gradually (baby steps) increase 
stimulus intensity by decreasing distance, 
increasing distractions, or moving to more 
challenging environments. • Progress is slow 
(typically months); however, immediate safety 
and welfare can be achieved if triggers can be 
identified and prevented or avoided; owners 
should be counselled on reading and 
monitoring body language to identify thresholds 
and avoid setbacks. • Owners must always be 
vigilant for stimuli that might incite fear or 
aggression. • Discuss whether referral to 
behavioral management, behavior modification, 
and medication.
Aggression may be lower in neutered animals, 
but opposite has also been reported.
canine aggression; owners must give informed 
consent that use is off‐label and be advised of 
potential side effects and risks. • Medications 
are likely indicated for moderately intense 
fear and anxiety, impulsivity, and reactivity. 
• Ensure that owners understand risks in 
owning an aggressive dog, that medication 
will not ensure safety, and that they must 
follow safety procedures. • Proper diagnosis 
with behavioral modification plan, together 
with appropriate selection of behavioral 
drugs, leads to most successful outcome.
appetite is common and usually transient.
• Clomipramine 1–3 mg/kg q12h (label‐  
sedation, GIT effects, anticholinergic effects, cardiac conduction disturbances if 
predisposed, agitation.
q8–12h. • Side effects—transient hyperglycemia, 
anticholinergic, hypotension, collapse, 
bradycardia, agitation.
8–10 mg/kg if no adverse effects. Use cautiously 
anorexia, ataxia, GIT effects, cardiac 
conduction disturbances, agitation.
eliciting triggers. • Side effects—sedation, 
Corticosteroids may contribute to polypha­
gia, increased food guarding, and irritability.
(TCAs), or monoamine oxidase (MAO) 
inhibitors (e.g., amitraz, selegiline), and use 
cautiously or avoid with opioids, tramadol, or 
other medications that increase serotonin—
can result in serotonin syndrome.
pheromones, supplements containing alpha‐
casozepine or l‐theanine, or a calming 
  FOLLOW‐UP
first 1–3 weeks after the consultation. 
Provisions for further follow‐up should be 
made at that time. • Drugs should only be 
prescribed under supervision and monitoring 
of veterinarian.PREVENTION/AVOIDANCE
lifelong.
Injuries to humans.
• Lifelong management is necessary. 
• Prognosis for improvement determined by 
managed; owner compliance; and level that 
might be achieved with behavior modification 
and medication. • Prognosis more favorable if 
aggression occurs at low intensity and in 
predictable situations.
possessive and redirected aggression, 
impulsivity, reactivity.
behavior.
SEE ALSO
• Aggression, Food and Resource Guarding—
Dogs. • Aggression, Overview—Dogs. 
• GIT = gastrointestinal tract. • MAO = 
monoamine oxidase. • SSRI = selective 
serotonin reuptake inhibitor. • TCA = 
tricyclic antidepressant.
Anim Behav Sci 2009, 177:47–54.
Blackwell, 2018, pp. 45–57.
Sueda KL, Malamed R. Aggression toward 
people—a guide for practitioners. Vet Clin 
N Am 2014, 14:599–628.
Authors  Wailani Sung and Jeannine Berger
Meredith E. Stepita and Laurie Bergman.
available onlineAggression Toward Familiar People—Dogs  (continued)

Canine and Feline, Seventh Edition  49
A Aggression Toward Humans—Cats
  BASICS
Human‐directed aggression in cats.
• Most common causes for human‐directed 
aggression in cats include play, fear/pain‐
related, redirected, maternal, and petting 
intolerance.
• Context contributes greatly when making 
correct diagnosis. For example, play aggression 
is likely to be seen in young, solitary cat, 
while pain‐related/fear aggression is common 
behavior seen in clinic setting.
• Behavioral.
• Gastrointestinal—decreased appetite if fear 
and/or pain related.
• Hemic/lymphatic/immune—chronic stress 
effects on immune function.
• Ophthalmic—dilated pupils in response to 
autonomic nervous system stimulation.
• Skin/exocrine—may show displacement 
behaviors such as overgrooming.
GENETICS
No known genetic basis.
Aggression is second to inappropriate elimin­
ation for feline cases seen by veterinary 
behavior specialists.
None
• Cats of any age, sex/neuter status, breed can 
be affected.
• Play‐motivated aggression more likely in 
juvenile, solitary cat.
SIGNS
• Play motivated—cat approaches its “victim,” 
crouches in wait, stalks and chases; tail is 
twitching and ears are forward. Typically will 
attack moving target.
• Fear/pain related—ears back, body and tail 
lowered, piloerection, pupils dilated; may hiss 
and growl. Avoidance of person(s) who elicit 
aggression. Attacks if approached and/or 
cornered. Extreme cases: expression of anal 
glands, urination, and/or defecation. Hiding 
behavior.
• Redirected—cat highly aroused by stimulus 
and seeks out alternate target. Aggression can 
be very severe given cat’s level of arousal.
• Maternal—usually predictable and self‐
limiting. Queen will act to protect her kittens.
• Petting intolerance—cat signals its 
“displeasure” by twitching its tail and skin 
when being petted in an undesired location 
and/or for too long. Ears usually back; 
mydriasis; may hiss and growl before turning 
to bite person.CAUSES & RISK FACTORS
• Play motivated—lacking in opportunities 
for normal play: solitary cat, insufficient and/
or inappropriate toys; history of owner using 
hands/feet to play with kitten and/or playing 
roughly with kitten.
• Fear—poor socialization with humans and/
or feral living, aversive event associated with a 
person, or people in general.
• Pain related—medical/physical condition 
such as abscess, especially in indoor/outdoor cat.
• Redirected—occurs during interference in, 
or interruption of, situations that have caused 
cat to become aggressively aroused, such as 
cat fight (between familiar household cats), 
presence of a cat outside, or noise.
• Maternal—recent birth of litter.
• Petting intolerance—etiology unknown. 
Cats tend to groom each other on head/neck, 
so human petting of cat in other locations 
may contribute to aggressive reaction.
  DIAGNOSIS
• To rule out contributing medical conditions 
and screening prior to drug use.
• Urinalysis if concurrent inappropriate 
elimination or marking.
Middle age/senior cats—thyroid profile.
IMAGING
If indicated based on clinical examination 
and/or suspected pain.
Thorough behavioral history, including 
description of cat’s postures during aggression and 
injuries inflicted, context, presence of outside 
cats, early historical information, litter box use, 
food consumption, and hiding behaviors.
N/A
  TREATMENT
Only if health/medical issue diagnosed.
ACTIVITY
• Play motivated—cat should be provided 
with increased opportunity for appropriate 
play, either in the form of toys, human 
interaction, or additional housemate.
• Redirected—cat should be denied access to 
windows where outside cats can be seen.DIET
Potential anxiolytic effects of “calming” diets 
(see Supplements).
• Play motivated—normal play behavior and 
importance of opportunities for appropriate play.
• Fear—avoidance of fear‐inducing 
situations: ongoing exposure may worsen 
signs, cause severe stress, and compromise 
welfare.
• Redirected—addressing primary stimuli, 
such as outside cats.
• Maternal—normal maternal and kitten‐
protective behavior; same as for fear‐
motivated aggression.
• Petting intolerance—normal feline 
grooming patterns; observation of cat’s 
warnings so that behavior does not escalate.
Behavior Modification Exercises
Desensitization and Counter‐Conditioning 
(DS&CC)
• Desensitization—exposing cat to fear‐
inducing stimulus (scary person) at a low level 
so cat does not react fearfully or aggressively. 
Over time, intensity of stimulus is increased 
(i.e., distance between cat and stimulus is 
decreased) without causing fearful responses.
• Operant conditioning (response substitution)—  
rewarding cat with special treat, toy, 
grooming, petting, for relaxation.
Classical Conditioning (CC)
Classical counter‐conditioning conditioning—  
pairing threatening stimulus (e.g., a person) 
with tasty treat, toy, petting; example: scary 
person = tuna fish.
Short‐term use of medication may be 
necessary to decrease overall levels of anxiety 
and reactivity in more severe cases.
Azapirones
• Buspirone 0.5–1.0 mg/kg PO q12h.
• Most useful for fearful and withdrawn cats; 
decreases 
anxiety and may increase “self‐confidence.”
• Anecdotal reports of “increase in affection,” 
therefore might be useful in severe cases of 
petting intolerance.
• Response noted in 1–2 weeks.
(SSRIs)
• Fluoxetine, paroxetine, sertraline 0.5–
1.5 mg/kg PO q24h.
• SSRIs must be given daily; may take 4–8 
weeks to reach peak effects.
• Amitriptyline 0.5–2.0 mg/kg PO q12–24h.
• Clomipramine 0.25–1.0 mg/kg PO q24h.

50 Blackwell’s Five-Minute Veterinary Consult  
A
• TCAs must be given daily; may take 4–8 
• Alprazolam 0.125–0.25 mg/cat PO 
q8–24h.
• Diazepam 0.1–1.0 mg/kg PO q12–24h 
(rarely used due to potential hepatopathies).
• Can be given “as needed” for specific 
encounters with people inducing fear 
response and during DS&CC and CC 
sessions.
• Can be used in conjunction with 
azapirones, SSRIs, and TCAs.
CONTRAINDICATIONS/PRECAUTIONS/
• None of drugs listed are approved for use 
in cats.
• All medications to be administered orally, as 
have not been shown to reach therapeutic 
levels by transdermal dosing.
• Azapirones—side effects uncommon, but 
occasional excitement noted; should not be 
given in combination with monoamine 
oxidase (MAO) inhibitor; avoid use in the 
aggressor cat as may increase any “bully” 
behavior.
• Neither SSRIs nor TCAs should be given 
with each other, nor in combination with 
MAOIs.
• SSRIs—side effects include mild sedation 
and decreased appetite, constipation, and 
urinary retention; competitive inhibition of 
cytochrome P450 liver enzymes; when 
administered concurrently with medication 
utilizing P450 enzymes, elevated plasma levels 
of medications may increase.
• TCAs—side effects include sedation, 
constipation, diarrhea, urinary retention, 
appetite changes, ataxia, decreased tear 
production, mydriasis, cardiac arrhythmias, 
tachycardia, and changes in blood pressure.
• Benzodiazepines—side effects include 
sedation, ataxia, muscle relaxation, increased 
appetite, paradoxical excitation, and increased 
friendliness; idiopathic hepatic necrosis has 
been reported in cats following treatment 
with diazepam.
• Specific recommendations for the use of 
diazepam—baseline physical exam, CBC, and 
blood chemistries to confirm good health; 
repeat the blood chemistries at 3–5 days; if 
elevated alanine aminotransferase (ALT) or 
aspartate aminotransferase (AST), discontinue 
medication.ALTERNATIVE DRUG(S)
Pheromones
• Used alone or concurrently with drugs.
• F3 facial pheromone (Feliway®) diffuser, 
spray, and wipes.
• Maternal pheromone—Feliway MultiCat 
(Friends) diffuser for feline social conflict.
• Maternal pheromone collar (NurtureCALM 
24/7).
Supplements
Used alone or concurrently with drugs:  
L‐theanine (Anxitane®); alpha‐casozepine 
(Zylkene®); combination products also 
containing thiamine, whey protein, and 
calming plant extracts (Solliquin®); or diets 
supplemented with alpha‐casozepine and  
l‐tryptophan (Multifunction Urinary + Calm 
Diet, Royal Canin®).
  FOLLOW‐UP
• Weekly follow‐up recommended in early 
stages of treatment.
• For cats on medication, follow‐up blood 
testing recommended every 6–12 months.
• Play motivated—provide opportunities for 
appropriate play.
• Fear—avoidance of fear‐inciting stimuli; 
early socialization to people and events may 
help prevent some occurrences of fear‐related 
responses to people.
• Pain—treat underlying conditions.
• Redirected—address possible arousing 
stimuli, indoors and outdoors.
• Maternal—as for fear.
• Petting intolerance—limit amount of time 
petting cat; DS&CC to petting.
Potential human injury, especially if cat is 
approached, cornered, and/or highly aroused.
• Progress occurs slowly; relearning is a 
process and each case is individual.
• If medications are indicated, begin at low 
dose and titrate up as necessary.
• To discontinue medication, wait until new 
behavior is stable (8–12 weeks) and wean off 
slowly, usually over weeks.
• If aggressive behavior recurs, return to 
lowest effective dose.  MISCELLANEOUS
N/A
AGE‐RELATED FACTORS
Play motivated—typically seen in young, 
solitary cat in household.
People injured during aggressive attack should 
seek prompt medical attention; infection by 
Bartonella henselae  can result from cat scratch 
or bite.
Avoid medications in breeding/nursing cats.
SYNONYMS
N/A
SEE ALSO
• Aggression, Overview—Cats.
• Fears, Phobias, and Anxieties—Cats.
• AST = aspartate aminotransferase.
• CC = classical conditioning.
• DS & CC = desensitization and counter‐ 
conditioning.
Bradshaw J, Ellis S. The T rainable Cat: A 
Practical Guide to Making Life Happier for 
You and Your Cat. New York: Basic Books, 
2016.
Blackwell, 2018, pp. 143–250.
Landsberg GM, Hunthausen W, Ackerman L. 
pp. 327–343.
Overall K. Manual of Clinical Behavioral 
Medicine for Dogs and Cats. St. Louis, 
MO: Mosby, 2013, pp. 390–426.
Seksel K. Behavior problems. In: Little SE, 
ed., The Cat: Clinical Medicine and 
Management. St. Louis, MO: Saunders, 
2012, pp. 219–224.
Author  Terry Marie Curtis
Consulting Editor  Gary M. LandsbergAggression Toward Humans—Cats  (continued)

Canine and Feline, Seventh Edition  51
A Aggression, Food and Resource Guarding—Dogs
  BASICS
OVERVIEW
• Aggression displayed while guarding food 
(e.g., in food bowl, dog “chews”), scavenged 
items, objects (e.g., toys, stolen objects), 
resting locations (e.g., bed, couch), or people. 
Usually within the range of normal behavior, 
but may be excessive or abnormal due to early 
experience, learning, genetic factors, or 
underlying medical conditions.
SYSTEM AFFECTED
Behavioral.
No breed or sex predilections.
SIGNS
• Barking, growling, lip-lifting, snarling, 
other dogs or people.
• Subtle communication signals may include 
blocking access to resources, hard stare, taller 
stance, tail elevated, and ears perked forward 
when in possession of valued resource.
• May be accompanied by fearful/submissive 
body postures/facial expressions (e.g., 
crouching, backing away, ears back, tail 
tucked, looking away, lip licking).
• Can be motivated by fear—defensive or 
offensive.
• Most common near valued resources (e.g., 
food), stolen items (e.g., tissues, owner 
clothing), scavenged items (e.g., garbage), and 
lasting items (e.g., chews).
• Underlying medical conditions, especially 
pain, endocrinopathies, gastrointestinal 
disease, or those causing changes in appetite.
• May be a normal canine behavior, 
influenced by previous negative experience 
(e.g., lack of socialization, physically 
removing resources, punishment or confron -
tation) or other behavioral disorders, such 
as anxiety.
• Owner’s inability to read and recognize 
signs of fear or conflict.
  DIAGNOSIS
• Fear aggression.
• Social status aggression.
• Conflict-related aggression.
• Generalized anxiety disorder.
• Pain-related aggression.
• Irritable aggression.
To rule out underlying contributing medical 
conditions.OTHER LABORATORY TESTS
conditions, particularly if signs of polyphagia; 
thyroid screen.
IMAGING
Gastrointestinal diagnostics.
  TREATMENT
GENERAL COMMENTS
• T reatment consists of a multifaceted 
approach including management to ensure 
modification, and medication (if indicated).
• A realistic expectation is for successful 
management, not full resolution. In most 
cases, owners will need to manage triggers for 
the rest of the dog’s life.
• Successful treatment depends on the owner’s 
communication, identifying and preventing 
all aggression-eliciting stimuli (e.g., situations, 
people, resources), willingness and ability to 
follow safety recommendations, and effective 
implementation of reward-based behavior 
modification.
• Owners must be educated about the risks of 
using physical punishment and training 
techniques that use “dominating,” such as 
alpha rolls, corrections with choke chains or 
prong collars, verbal punishment, and of 
physically taking away resources that can lead 
to increased aggression, anxiety, and resource 
guarding, and disruption of the human–
animal bond.
SAFETY RECOMMENDATIONS
• Prevention/avoidance is essential to ensure 
safety, address the pet’s welfare, and prevent 
further repetition and potential intensification 
of the problem.
• Safety measures include training dogs to 
wear a basket muzzle, placing head collars or 
harnesses with leashes attached, and the use 
of pet gates and confinement training to 
prevent access to resources that might be 
guarded.
• Confine the dog away from potential 
victims and items and/or keep people away 
from the dog when it is in possession of 
resources that might be guarded; alternately, 
the dog must be under direct physical control, 
(e.g., with leash attached), of a responsible adult.
• Identify and prevent or avoid any situation 
that might trigger aggression. Never forcibly 
remove objects in the dog’s possession. Wait 
until the dog is finished with the resource and 
will walk away, or cue and reward the dog for an alternative behavior, (e.g., drop, touch) 
(see training below).
• If the dog is in possession of an object that 
must be removed for safety, offer a reward 
(e.g., treat, toy, walk) of higher value or use a 
stimulus (e.g., doorbell) that will move the 
dog away.
• If safety cannot be ensured, the dog should 
be removed from the household.
BEHAVIOR THERAPY
• Structured interaction programs where the 
dog is taught to consistently perform a 
treats, going for a walk) give the dog control 
of its resources for being calm, provide 
structure and predictability in all interactions, 
teach impulse control, and train the dog 
using positive interactions (e.g., good things 
happen by sitting calmly).
• Provide sufficient outlets for play, chew, and 
feeding, such as in food-filled toys in 
locations and at times where the dog can be 
left alone or physically confined, (e.g., to a 
room, behind a barrier, or in a safe haven 
(pen, crate)) until the dog finishes with the 
resource, will walk away, or can be cued away 
and rewarded.
• T raining—focus on teaching behaviors in 
neutral situations using positive reinforcement 
(e.g., food, toys, play, petting) that can be 
used to:
 ◦Keep the dog away from resources, (e.g., 
leave it, go to bed or crate, or watch).
 ◦Move the dog away from resources, (e.g., 
touch (hand target), find it).
 ◦Release the object (e.g., drop).
• Private sessions with a force-free trainer 
may provide the best guidance for successful 
training.
• Behavior modification—desensitization 
(DS) is the process by which dogs are exposed 
to their triggers under their threshold (e.g., 
distance, low-value resource). Food, toys, 
verbal praise, or attention/petting can be used 
as rewards for calm responses. Counter-
conditioning (CC) is the process in which 
favored rewards are paired with the stimulus 
to change the emotional response to one that 
is positive. 
• Gradually (baby steps) increase stimulus 
intensity, staying below the threshold that 
would result in fear and/or aggression, (e.g., 
decreasing distance, increasing resource value, 
changing environments).
• The owner can toss treats when walking by 
the food bowl at sufficient distance that the 
pet associates approach with a positive outcome 
in association with the food bowl and toys.
• Progress is slow (typically months). 
setbacks.
• Owners must be vigilant to prevent approach 
in situations where dog might guard.

52 Blackwell’s Five-Minute Veterinary Consult  
A
• Discuss referral to a veterinary behavior 
specialist where recommended for assessment 
and counseling.
• Medications are generally not indicated for 
resource guarding.
• May be indicated for moderate to marked 
fear or anxiety, or when behavior is abnormal 
in intensity, reactivity, or impulsivity.
• Owners must receive informed consent of 
potential risks and side effects, that the use of 
a medication is off-label, and that medication 
does not insure safety.
• For ongoing medication, a selective 
serotonin reuptake inhibitor (SSRI; e.g., 
fluoxetine, paroxetine, sertraline) or 
clomipramine might be indicated.
• For situational or as needed use, trazodone, 
clonidine, or benzodiazepines might be 
considered alone or in conjunction with an 
ongoing medication.
• For doses, side effects, precautions, and 
contraindications, see Aggression toward 
Familiar People—Dogs.
• Use caution, as any psychotropic medic -
ation might cause undesirable changes in 
behavior, including increased irritability and 
aggression. Drugs that increase appetite (e.g., psychotropic drugs, steroids) may increase 
• Corticosteroids can be contraindicated 
in food‐aggressive dogs; could cause or 
contribute to polyphagia, resource guarding, 
and irritability.
  FOLLOW-UP
In most cases, follow-up should be within the 
for further follow-up should be made at that 
time.
Owner should receive counseling from first 
visit on socialization, making positive 
associations with handling, reward-based 
training to cues (including touch and drop), 
and never forcing a pet to relinquish 
resources.
lifelong management is usually necessary.
severity of aggression, number and type of 
resources guarded, and whether they can be 
effectively identified and prevented.
• Prognosis is highly dependent on owner 
compliance.  MISCELLANEOUS
Other fear- or anxiety-related conditions.
Human injury and bite wounds.
behavior.
SEE ALSO
• Aggression to Unfamiliar People and 
Unfamiliar Dogs—Dogs.
• Aggression toward Familiar People—Dogs.
• CC = counter-conditioning.
• DS = desensitization.
Behavior, 2nd ed. Hoboken, NJ: Wiley-
Blackwell, 2018, pp. 100–109.
Meredith E. Stepita and Laurie Bergman.Aggression, Food and Resource Guarding—Dogs  (continued)

Canine and Feline, Seventh Edition  53
A Aggression, Intercat Aggression
  BASICS
Intercat aggression—offensive or defensive 
aggression between cats consisting of staring, 
displacing, vocalizing (growling, yowling, 
shrieking), spitting, hissing, swatting, lunging, 
chasing/stalking, and/or biting other cats.
• May be normal behavior or abnormal. 
• May be caused by underlying medical 
disease (e.g., CNS) or concurrent medical 
disease that may lower the threshold for 
irritable responses (e.g., pain, hyperthyroid). 
• May be multiple motivations including 
predatory/play, disputes over territory, sexual, 
fear, anxiety, and redirected, fear, anxiety, 
non-recognition, and redirected.
• Behavioral. • Skin/exocrine—secondary to 
traumatic injury. • Immune—chronic stress 
may alter the immune response. • Secondary 
infection (cat bite abscesses) is not uncommon. 
• Nervous.
GENETICS
None. However, friendliness may be mostly 
related to paternal effects.
Unknown
None
• Can occur at any age due to changes in social 
environment or be redirected. • Previously 
stable relationships can deteriorate as cats reach 
social maturity (2–4 years of age).
Sex
• Intact males more likely to initiate intercat 
aggression (related to territory, and/or 
proximity to females). • Females will defend 
their young from unfamiliar individuals. 
• Male kittens more likely to initiate intercat 
aggression related to predatory components 
of play.
SIGNS
• May arise spontaneously and vary in 
frequency and intensity. • Owners most likely 
to seek behavioral intervention if there are 
physical injuries, the welfare of the aggressor 
and/or victim is compromised, or fighting 
becomes sufficiently distressing. • Human 
attempts to interrupt fighting may trigger 
human-directed aggression/injury.
Aggressor (Usually Offensive)
• Covert signs—staring, displacing other cats, 
stiff body language/movements while 
approaching other cat. • Overt signs—growling, yowling, spitting, hissing, swatting, 
lunging, chasing/stalking, and/or biting other 
cats, dilated pupils, may be accompanied by 
body language of fear (e.g., classic Halloween 
cat stance: piloerection, back arched, tail up) 
or more offensive body language (tense 
muscles, tail head elevated but rest of tail 
down, back straight or slightly slanted toward 
head, ears forward or to the side), excessive 
facial marking, and perhaps urine marking.
Victim (Usually Defensive)
• Covert—avoidance of aggressor, hiding, 
change in grooming and eating habits, hyper- 
vigilance, dilated pupils. • Overt—hissing, 
swatting, running, vocalizing (including 
growling), Halloween cat stance, may escalate 
to defensive attack if cornered.
Elimination Outside of Litter Box
• Aggressors may block access to litter box 
area, forcing victims to choose alternative 
locations; secondary substrate and/or location 
preferences and aversions can develop. • Both 
victims and aggressors may urine mark. 
• Extremely fearful cats may urinate or 
defecate in midst of aggressive events.
Physical Examination
• Normal, except injury from fights or if 
underlying medical issues. • Stress may affect 
eating and self-grooming (increased or 
decreased).
CAUSES
• Lack of appropriate socialization to other 
cats prior to 7 weeks of age. • May be 
component of normal social behavior.  • Social 
and environmental instability such as addition 
of new cat, loss of resident cat, odor stimuli 
(return of cat from veterinarian or giving one 
cat a bath), aging or illness of one or both cats, 
cats reaching social maturity. • Household 
change, e.g., moving, changing furniture or 
resting areas. • Genetically unrelated cats and 
cats that have recently moved in together are 
more likely to show aggressive behaviors 
toward each other. • Resident cats commonly 
need prolonged exposure to new cats before 
accepting them into group. • Resource 
limitation, e.g., vertical and/or horizontal 
space, hiding/resting areas, food, water, and 
litter boxes in multicat households. • Exposure 
to arousing stimuli (cats in yard, visitors, 
noises, scents, etc.) can cause redirected 
aggression, after which aggression might 
persist. • Medical problems including CNS 
disorders, hyperthyroidism, or any disorder 
that causes pain and/or increased irritability.
• Singleton and/or bottle-raised kittens. 
• Lack of socialization exposure and 
experience with conspecifics during socializ- 
ation period (2–7 weeks) and beyond. • Male 
intact cats. • Postpartum females with kittens. 
• Separating and returning housemate (e.g., 
following veterinary visit, groomer). • Changes in social group such as addition of 
“new” cat. • Scratching and biting during 
first introduction. • Access to outdoors  
and/or intrusion of unfamiliar cats onto 
territory. • Crowding or lack of adequate 
social space and access to resources.
  DIAGNOSIS
Behavioral Differentials
• Fear-related aggression—cat may hiss, spit, 
arch the back, display piloerection, and 
attempt to flee unless escape is thwarted; 
pupil dilation will accompany a fear response. 
• Status-related aggression—may occur with 
change or instability of social hierarchy and 
control of access to resources; it is undecided 
if cats have dominance hierarchies or if 
conflict is better explained by territorial 
defense. • Territorial aggression—in response 
to threat to territory; boundaries marked with 
urine, feces, or scent glands. • Redirected 
aggression—exposure to agitating stimuli 
(cats in yard, visitors, noises, scents, etc.), 
with aggression directed toward target other 
than stimulus. • Failure of recognition—
aggression between feline housemates after 
returning from separation (e.g., veterinary 
visit, grooming); most likely due to change in 
odor, visual cues, or stress of returning cat. 
• Maternal aggression—aggression during 
periparturient period; females guard kittens 
and nesting sites. • Intermale aggression—
between males in response to territorial 
disputes, hierarchical status, or mates; may be 
more pronounced at social maturity. • Sexual 
aggression—male typical behavior of chasing, 
pouncing, biting on nape of neck, and 
mounting. • Predatory/play-related aggression—  
predatory components of play directed 
toward another cat; recipient often older cat 
that is not interested in playing.
Medical Differentials
• Any illness causing malaise, pain, or 
increased irritability. • Endocrine—e.g., 
hyperthyroidism. • Neurologic—e.g., 
neoplasia, seizures, cognitive decline. 
• Infectious—e.g., toxoplasmosis, feline 
immunodeficiency virus (FIV), feline 
leukemia virus (FeLV). • Iatrogenic—
medications that increase irritability or 
disinhibit aggression (e.g., mirtazapine, 
benzodiazepines, buspirone). • Toxins—lead, 
illicit substances.
To rule out medical causes and as baseline if 
drug therapy indicated.
• FeLV/FIV. • Total thyroxine (T4) in cats 
>6 years.

54 Blackwell’s Five-Minute Veterinary Consult  
A
IMAGING
As indicated based on history and physical 
signs.
• Detailed behavioral and medical history. 
• Identify if there is a clear aggressor and/or 
victim and if aggression is overt or covert.  
• If multiple cats, determine which cats spend 
time together and mutually groom, and 
which avoid each other. • Identify preferred 
core areas of each cat for feeding, play, and 
resting, and locations of any house soiling or 
marking. • Identify number, location, types 
of litter boxes, and their management. 
• Videos, photographs, and/or drawn floor 
plans can provide spatial details and infor- 
mation regarding body language during social 
interactions. • Note any other changes in 
demeanor, routine, eating, and grooming.
None unless concurrent medical diseases.
  TREATMENT
T reat as outpatient.
Supportive care if any injuries.
ACTIVITY
• May need to be restricted if confinement 
required to prevent perpetuation of aggression 
and negative emotional responses.
• Provide sufficient alternate outlets for each 
cat during confinement and during release.
For chronic, severe cases or for aggression that 
does not respond to treatment, may require 
permanent separation, either by rehoming one 
of the cats or by confining them in separate 
parts of the home.
Cases with Low Frequency of Intense, 
Injurious Aggressive Outbursts
• Separate cats when they cannot be super  - 
vised (create “safe zones”). • Either keep 
separate in same areas each day in effort to 
form separate core territories for each cat, or 
“time share” space between cats. • Confine 
newly introduced cat or aggressor to smaller, 
less familiar area. • For multiple cats, 
separate by stability of relationship between 
cats. Any despotic/bully cats should be 
confined alone. • Consider “artificial 
allomarking” to form communal scent 
between cats that are fighting; a towel 
(facecloth) may be rubbed (cephalocaudally) 
to obtain scent of one cat and then rubbed 
onto other cat, and vice versa. • Towels 
should be left in environment to allow for 
habituation to each other’s scent, especially if 
cats are kept separated. • Reward cats with 
food, play, and/or attention for being in same room together without having aggressive 
events. Cats should stay at a distance that 
allows for calm participation. • Engage cats 
in daily sessions of pleasurable activities (e.g., 
play, training, eating delectable food treats) 
at distances that do not incite aggression. 
Gradually move fun sessions closer to each 
other, making sure to stay at a distance that 
does not trigger overt/covert aggression. 
• Teach cats a “come and/or go to place” cue 
using positive reinforcement at times, in 
situations, and with sufficient rewards that 
cats are most able to learn.  • Interrupt or 
redirect cats by cueing to come or go to their 
place, or by luring one or both cats to their 
safe zones with food, treats, wand toys, tossed 
toys, or laser pointers before aggression starts 
or as initial signs are seen (e.g., staring, tail 
twitching, pupil dilation). • Aversives and/or 
punishers can increase aggressive behavior 
and increase negative associations with other 
cats, so must be avoided. • Goal of manage -
ment and safety is to prevent aggressive 
events. In an emergency, use of laundry 
basket or blanket placed between or over cats 
can stop aggression, and direct cat to its safe 
area until calm, but should not be considered 
as a standalone treatment. • Bell the 
aggressor (using quick release or safety collar) 
so both owners and victim can quickly 
identify his or her location. • Increase 
number of resources and locations (e.g., 
food, water, scratching, perching, bedding, 
play and feeding toys) throughout the 
residence, including each cat’s core area. 
Efficacy of multimodal environmental 
enrichment should not be underestimated. 
• Increase litter boxes to number of cats plus 
one divided among multiple locations, so 
that one cat cannot keep another from 
accessing boxes; locations with more than 
one exit/entry are ideal. • Increase number of 
hiding and resting areas, especially by 
increasing vertical space (e.g., shelves, 
window sills). • No new cats should be 
added to the house.
Cases Where Cats Cannot be in Same 
Room without Immediately Becoming 
Agitated
• Separate cats completely when 
unsupervised. • Meet each cat’s needs for 
play, litter boxes, food, water, perching, 
resting, and attention. • Large wire dog 
kennel or vertically oriented wire cat cage 
(with shelving) may be better tolerated than 
smaller cat kennels and can be used for 
controlled exposure. • Cats may be taught 
to tolerate harnesses and leashes so that they 
can be used during training and controlled 
reintroduction. This is especially valuable for 
the aggressor. • Set up desensitization and 
counter-conditioning sessions daily; initially 
utilize physical and visual barriers (e.g., 
opposite sides of solid door). • Proceed to controlled visual introduction, across glass or 
screen door, in their kennels, or on leash and 
harness, insuring they are at a distance that 
prevents overt/covert aggression. Feed cats or 
engage in play for classical counter-
conditioning. • Over many sessions gradually 
reduce distance between cats, being careful 
to stay far enough apart during each session 
that no overt or covert behavioral signs of 
aggression and/or fear are seen. Start and 
end all sessions on successful note. • Teach 
each cat a “come and/or go to place” cue 
using operant counter-conditioning and 
positive reinforcement at times when cats are 
not stressed. Practice several times daily so 
each cat learns to respond reliably. • When 
ready to allow cats more freedom with each 
other, follow instructions for less severe 
intercat aggression (above).
Neutering reduces roaming, intercat 
aggression, and urine spraying in approxi- 
mately 90% of intact males. Neutering/
spaying reduces mounting and sexual 
behavior.
As all medications are extra-label, insure 
client is informed, and review target desirable 
outcomes and potential adverse effects.
For Aggressor and/or Victim
(SSRIs)
• Fluoxetine or paroxetine 0.5–1 mg/kg PO 
q24h. • Drugs of choice for aggression, 
anxiety, and/or urine marking; may decrease 
impulsivity. • Side effects may include 
gastrointestinal upset, decreased appetite, 
sedation, urinary retention, constipation, 
lowered seizure threshold, and increased 
agitation/irritability.
• Clomipramine 0.25–0.5 mg/kg PO 
q24h—serotonin selective tricyclic, for 
anxiety and aggression. • Side effects include 
gastrointestinal upset, sedation, urinary 
retention, constipation, and lowered seizure 
threshold. Do not use in patients with 
arrhythmias or cardiomyopathies.
• Feliway® Multicat/Friends (Ceva)—
synthetic feline mammary gland pheromone 
that may be helpful for reducing intercat 
social conflicts when combined with a 
multimodal plan. • Feliway Classic (Ceva)—
synthetic feline facial pheromone that may be 
helpful in reducing stress and associated 
marking behavior.Aggression, Intercat Aggression  (continued)

Canine and Feline, Seventh Edition  55
A
For Victim
Azapirone
• Buspirone 0.5–1 mg/kg PO q8–24h—
reserved for victims to increase social 
confidence. • Side effects rare; may include 
decreased sociability and increased agitation/
irritability; victim may be more confident and 
fight back.
• Lorazepam 0.125–0.25 mg/CAT PO up to 
q12–24h or oxazepam 0.2–0.5 mg/kg PO 
q12–24h for anxious or fearfully aggressive 
cats and as an appetite stimulant, helping 
to facilitate classical counter-conditioning; 
may be used as needed, with peak effects 
seen within 1 hour. • Side effects may 
include increased appetite, ataxia, inhibited 
learning, and disinhibition of aggression. 
• Note: controlled substance; dependence 
can develop; should be gradually weaned if 
used consistently for longer than 2 weeks.
• Benzodiazepines should be used cautiously 
or avoided in cats with hepatopathies. • SSRIs 
and TCAs may produce anticholinergic side 
effects. • SSRIs and TCAs should be used 
with caution in patients with cardiac 
abnormalities, seizures, and liver disease.
• Any behavioral drug may produce para  - 
doxical reactions, including fear, anxiety, 
hyperexcitability, and/or aggression. 
• Medications that alter serotonin levels 
have the potential to produce serotonin 
syndrome.
• Avoid concurrent use of SSRIs and TCAs; 
avoid using monoamine oxidase inhibitors 
(MAOIs, such as selegiline) with SSRIs and 
TCAs; use SSRIs and TCAs cautiously or 
avoid with buspirone, tramadol, and 
tryptophan due to possible serotonin 
syndrome. • Caution with concurrent 
medications considered substrates of 
cytochrome P450.
• Amitriptyline (TCA) 0.5–1 mg/kg PO 
q12–24h—for anxious cats, especially if 
comorbid recurrent feline idiopathic cystitis/
feline lower urinary tract disease (FIC/
FLUTD); not selective for serotonin reuptake 
inhibition and likely less effective for 
aggressor. Side effects include sedation, 
decreased grooming, and increased weight. 
• Dietary supplementation with l-theanine (Anxitane, Virbac), or with alpha-casozepine 
(Zylkene®, Vetoquinol), Royal Canin 
Veterinary Diet Calm® (contains alpha-
casezopine, l-tryptophan, and nicotinamide), 
or Hill’s Prescription Diet® Multicare Feline 
Urinary Stress (contains l-tryptophan and 
milk protein hydrolysate).
  FOLLOW-UP
• Monitor patients 2 weeks after treatment 
initiation and monthly for first few months; 
follow-up visit should be scheduled 4–8 
weeks into treatment if drugs dispensed to 
assess response and adjust dose if necessary. 
• Benzodiazepines may rarely cause cases of 
fatal hepatopathies; patients should be 
rechecked immediately if any adverse events 
occur, including anorexia. • Medication 
should be used for at least 4–6 weeks after 
resolution of signs, then gradually weaned by 
reducing dosage no faster than 25% per day 
on weekly basis. • Some patients require 
long-term medication; recheck laboratory 
work every 6 months to 1 year, depending on 
health and age.
• Proper socialization through 2–7 weeks of 
age and ongoing. • Gradual introduction more 
closely resembles natural process through 
which new cats enter existing group at the 
periphery and may be accepted over time. 
• Negative initial encounter often associated 
with future intercat aggression. • Related and 
familiar cats less likely to have intense intercat 
aggression. • In stable multicat households, 
avoid adding additional cats. • Avoid reintro  - 
duction aggression by avoiding separating cats 
when possible.
Abrupt withdrawal of behavioral medic-  
ations may result in aggression and rebound 
anxiety.
• Prognosis for most cases is fair; complicated 
by prolonged duration, high intensity, under- 
lying medical conditions, and incomplete 
owner compliance. In one study 62% were 
considered cured and 37% not cured 
(rehomed, euthanized, or permanently 
separated). • Recent and mild cases may have 
better long-term outcomes.  MISCELLANEOUS
• Urine marking/spraying. • House soiling.
• Excessive grooming. • Fearful/anxiety-
related behavior. • Human-directed or 
interspecies aggression.
Predatory/play-related aggression more 
common in young active and playful cats 
housed indoors with more sedentary or aged 
individuals.
Human intervention may lead to bite or 
scratch injuries.
Most behavioral medications are contra -
indicated in breeding animals.
SYNONYMS
Feline intraspecies aggression.
SEE ALSO
• Kitten Behavior Problems.
• FIC/FLUTD = feline idiopathic cystitis/
feline lower urinary tract disease.
• MAOI = monoamine oxidase inhibitor.
• T4 = thyroxine.
• https://indoorpet.osu.edu/cats • https://
catvets.com
Heath S. Feline aggression. In: Horwitz DF , 
Mills D, eds. BSAVA Manual of Canine and 
Feline Behavioural Medicine, 2nd ed. 
Gloucester: BSAVA, 2009, pp. 223–235.
Feline aggression. In: Behavior Problems of 
the Dog and Cat, 3rd ed. Philadelphia, PA: 
Elsevier Saunders, 2013, pp. 327–343.
Pachel CL. Intercat aggression: restoring harmony 
in the home. A guide for practitioners. Vet Clin 
North Am 2014, 44:565–579.
Authors  E’Lise Christensen Bell and Kenneth 
M. Martin
Consulting Editor  Gary M. Landsberg(continued)  Aggression, Intercat Aggression

56 Blackwell’s Five-Minute Veterinary Consult  
A
  BASICS
• Aggression is a behavioral strategy used to 
manage aversive situations. • May be normal and 
appropriate in certain contexts. • May be 
abnormal with deleterious effects on cat’s physical 
and emotional well‐being. • Aggressive—
describes both mood and temperament traits 
relating to propensity to show aggression when 
environmental circumstances dictate.
Play Aggression (toward People)
• Typically refers to cat who scratches and 
bites owners during play. • Not true 
aggression, but overzealous play without 
proper impulse control due to lack of training 
or proper intraspecific social feedback. • Cat’s 
intent is not to harm the person. • Behavior 
encouraged and rewarded by owners through 
rough play with kitten; when larger and 
stronger, becomes perceived as aggression 
rather than overzealous play.
Predatory Aggression (toward People or 
Other Animals)
• Cats have innate drive to “hunt” or show 
predation, which includes stalk, hide, and 
pounce. • Predatory behavior is not a direct 
function of hunger. • Typically stimulated by 
fast movements and can progress to cat 
hiding and waiting for animal or person to 
walk by. • Play is way for young cats to 
perfect predation skills; play aggression and 
predatory aggression may overlap.
Redirected Aggression (toward People 
or Other Animals)
• Cats who see, hear, or smell a trigger and 
direct aggressive behavior toward the closest 
bystander. • In some cases, one person or 
animal in the home becomes designated 
victim, and cat may bypass a nearby 
individual and attack preferred target. • Cats 
may remain aroused for 24–72 hours after 
triggering event. • Common triggers inciting 
redirected aggression are seeing another cat or 
wildlife outside or loud noises.
Fear/Defensive Aggression (toward 
People or Other Animals)
• Cat will show body postures indicative of 
fear/anxiety and may use aggression as strategy 
to manage that aversive situation. • Typical 
behaviors include combination of any of the 
following: hissing, spitting, piloerection, 
arched back, turning away, running away, 
cowering, rolling on back, and pawing 
(defensive) if cornered. • With learning and 
repetition, may display more offensive signs.
Territorial Aggression (toward People or 
• Some cats, particularly males, show territorial 
behavior in domestic home settings due to perceived need to defend multiple resources 
(e.g., people, food, resting areas, feeding areas, 
elimination sites, etc.). • Territorial behaviors 
include marking with urine and/or feces, 
bunting (rubbing of cheeks on surfaces to 
deposit pheromones), and scratching (also 
deposits pheromones and leaves visual mark) 
that may be associated with aggression. • In 
severe cases, aggressor may seek out the other 
individual and attack. • Body posture with 
territorial aggression is assertive and confident.
Pain Aggression (toward People 
and Animals)
Cats in pain may show aggression (hiss, 
growl, scratch, bite) when physically handled 
or immediately prior to or after activity such 
as jumping on or off a piece of furniture.
Maternal Aggression
Female cat may show aggressive behavior 
toward individuals approaching her kittens.
Impulse Control Aggression
Cats who show intense aggressive responses to 
mild stimuli without much or any warning 
may have impulse control disorder arising 
from dysfunctional serotonin neural circuits.
Frustration‐Induced Aggression (to 
People and Other Animals)
Some cats with very outgoing, social personali -
ties may exhibit aggression if restricted life 
indoors does not meet their behavioral needs.
Contact‐Induced/Petting Aggression 
(toward People)
• Cats may show early signs of aversion during 
petting and handling with ears going back and 
tail swishing. • If physical contact continues, 
they may bite. • Owners often miss early 
warning signs. • When cats groom one another, 
they typically limit grooming to the head 
region. • Some cats appear to be particularly 
sensitive to being stroked along the dorsum.
Intercat Aggression within Home
• After introducing new cat to home, 50% of 
cat owners report fighting (scratching and 
biting). • Number of cats, sex, and age are not 
significant factors in predicting which cats will 
show aggression toward each other. • Any of 
the above categories of aggression are all 
possibilities for fights between or among cats. 
• Fear/anxiety is most common cause of 
intraspecific aggression. • Learning—conse -
quences/outcome (reinforcement, punish -
ment) further compound the problem.
Behavior problems are typically multifactorial in 
cause. Figure 1 illustrates some of the common 
components that need to be evaluated to 
accurately diagnose and treat aggression cases.
• Behavioral—vary with type of aggression, 
occur alone or in combination: tail swishing/
twitching, ears turned sideways or flattened, stiffening of shoulders/legs, crouching, dilation 
of pupils, hissing, spitting, growling, piloerec -
tion, staring, chasing, stalking, pawing, lunging. 
• Cardiovascular—signs associated with 
sympathetic activation and hypothalamic‐pitui -
tary‐adrenal (HPA) activation. • Endocrine/
metabolic—long‐term aggression associated 
with fear/stress/anxiety, symptoms associated 
with long‐term activation of HPA system. 
• Gastrointestinal (GI)—with chronic HPA 
stimulation: may see cat more prone to 
anorexia and GI ulcers; with acute fear 
aggression: evacuation of bowel and possible 
diarrhea; inflammatory bowel disease (IBD) 
possible in chronic stress. • Hemic/lymphatic/
immune—decreased immune response with 
chronic HPA stimulation; stress leukogram. 
• Both victim and aggressor may suffer injuries; 
with chronic activation of HPA, muscle wasting 
may occur. • Nervous—increased reactivity up 
to 72 hours following aggressive event; may see 
increase in aggression with decreased provoca -
tion as synapses in amygdala become sensitized; 
in some animals may be associated with 
decreased serotonin, causing aggressive 
outbursts; may see ritualized motor patterns, 
shaking, or trembling. • Ophthalmic—dilated 
pupils with sympathetic stimulation. • Renal/
urologic—may see spraying or small amounts 
of urine on horizontal surfaces; stress may be 
contributor to feline interstitial cystitis. 
• Respiratory—tachypnea in acute cases or 
when stressed. • Skin/exocrine—damage due 
to fights or to excessive grooming associated 
with fear/anxiety/distress.
• Preliminary evidence that behavioral traits 
in cats vary by breed and sex. • Males more 
likely to show aggression toward other cats, 
while females more likely to show aggression 
toward owners. • Abyssinian, Russian blue, 
Somali, Siamese, and chinchilla breeds showed 
more aggression. • Maine Coon, ragdoll, and 
Scottish folds showed least aggressiveness.
SIGNS
• May appear at social maturity (2–4 years of 
age) except for play‐related and should occur 
in specific social contexts/interactions. If 
onset occurs in older cat, medical causes 
should be ruled out first. • General com-
ments—most owners able to detect overt 
signs of aggression (biting, hissing, growling), 
but may miss more subtle signs of aggression 
that typically occur between cats (staring) and 
resulting anxious behaviors that can result in

SIGNS
resulting anxious behaviors that can result in 
aggression (meatloaf position, averting gaze, 
etc.). Videotapes of intercat interactions allow 
clinician to assess behavior.
CAUSES
• Underlying medical issues can cause 
aggression. • Temperament/behavior 
influenced by genetics, rearing, socialization, 
environment in which cat lives, and types of 
interactions cat has with people.Aggression, Overview—Cats

Canine and Feline, Seventh Edition  57
A
  DIAGNOSIS
• CNS diseases (e.g., infections, toxins, 
tumors, partial seizures, focal seizures). 
• Hyperthyroid. • Hepatic encephalopathy. 
• Any condition causing pain (e.g., arthritis, 
pancreatitis, dental disease, anal sacculitis, 
diabetic neuropathy). • Lead poisoning.
CBC/CHEMISTRY/URINALYSIS
Physical examination, baseline blood, and 
urine screening followed by additional 
diagnostics as indicated based on history, 
examination, and laboratory results.
• Discuss Bartonella  testing in any cat that 
bites or scratches people. • Thyroid levels. 
• Urinalysis ± culture if house soiling. 
• Feline serology—feline calicivirus (FCV), 
feline leukemia virus (FeLV), female immuno-  
deficiency virus (FIV).
  TREATMENT
• Never use physical correction/punishment; 
may escalate aggression. • Never try to 
physically handle or manipulate a cat in an 
aggressive state. • Avoid known triggers. 
• Identify triggers and desensitize and 
counter‐condition to triggers. • Implement 
safety measures (nail caps, wearing long 
pants/long sleeves, keep flattened cardboard 
boxes around home to place between target 
and cat, redirect behavior in early arousal 
phase). • Behavior modifications to redirect 
cat and reduce arousal (specific plans 
dependent upon specifics of each case). 
• T rain cat to commands such as “sit,” “go to 
place,” etc. • Environmental enrichment and 
meeting behavioral needs. • Teach owners to 
identify early signs of arousal so cat can be redirected or so they can avoid cat. • After 
aggressive outburst, keep aggressor isolated in 
a room for at least 24 hours (as long as cat 
remains aroused after attack). • Pheromones. 
• Medications.
• Selective serotonin reuptake inhibitors 
(SSRIs)—fluoxetine or paroxetine 0.5 mg/kg 
PO q24h. • T ricyclic antidepressants (TCAs)—
clomipramine 0.25–1.0 mg/kg PO q24h. 
• Buspirone at 0.5–1.0 mg/kg q8–24h, 
benzodiazepines such as oxazepam at 0.2–
0.5 mg/kg q12–24h, or lorazepam 0.125–
0.25 mg/cat might reduce fear and build 
confidence and support counter‐conditioning 
in fearful cat that avoids or retreats.
• Cats with renal or hepatic disease. 
• Caution with TCAs and SSRIs in diabetics. 
• TCAs in patients with cardiac 
abnormalities.
• TCAs and SSRIs should not be used 
together. • Mirtazapine should be used 
cautiously in combination with TCA or SSRI. 
• Practitioner should evaluate all drugs and 
natural supplements administered to verify 
safety in combination.
• Amitriptyline 0.5–1.0 mg/kg PO q12–24h. 
• S‐adenosyl‐L‐methionine‐tosylate disulfate 
(SAMe) 100 mg PO q24h. • Alpha‐casozepine 
75 mg (15 mg/kg or greater) PO q24h. 
• l‐theanine 25 mg PO q24h. • Cat‐appeasing 
pheromone (Feliway® Multicat or Friends). 
• F3 cheek gland pheromone (Feliway). 
• Calming and stress diets containing alpha‐
casozepine and l‐tryptophan.
  FOLLOW‐UP
• Call owners once every 1–2 weeks for first 
2 months after treatment plan has been 
recommended; determine implementation of 
safety recommendations and behavioral plan. 
• If medication dispensed, dose should be 
reevaluated every 3–4 weeks. • Frequency of 
follow‐up will be dictated by severity of case 
and owner compliance. • CBC, chemistry, T4 
prior to medication; recheck liver and kidney 
values 2–3 weeks after starting medication; 
recheck bloodwork annually in young healthy 
patients, semiannually in older patients. • Repeat physical exams in older patients 
semiannually, as painful conditions may 
exacerbate aggression.
• Depends on type of aggression and compli -
ance of clients with suggested behavior plan. 
• Most cases need combination of behavioral 
modification, environmental modification, 
training, and, when necessary, medication. 
• Some types of aggression can resolve or 
improve within a few weeks, whereas others 
may take several months or longer. • Some 
forms of aggression have poor prognosis.
• Older cats—cognitive decline, CNS disease, 
arthritis, meningioma, other medical conditions. 
• Age 2–4 years—social maturity, when cats 
may start to show certain kinds of aggression.
SEE ALSO
• Aggression, Intercat Aggression. 
• Aggression Toward Humans—Cats.
• FCV = feline calicivirus. • FeLV = feline 
leukemia virus. • FIV = feline immunodefi-
ciency virus. • GI = gastrointestinal. • HPA = 
hypothalamic‐pituitary‐adrenal. • IBD = 
inflammatory bowel disease. • SAMe = 
S‐adenosyl‐L‐methionine‐tosylate disulfate. 
Bain M. Feline aggression toward family 
members: a guide for practitioners. Vet Clin 
North Am Small Anim Pract 2014, 
44:581–594.
Crowell‐Davis SL, Murray T, Dantas L. 
Veterinary Psychopharmacology, 2nd ed. 
Hoboken, NJ: Wiley, 2018.
Levine ED, Perry P , Scarlett J, et al. Intercat 
aggression in households following the 
introduction of a new cat. Appl Anim 
Behav Sci 2004, 90:325–336.
Pachel C. Intercat aggression: restoring 
harmony in the home: a guide for practi-
tioners. Vet Clin North Am Small Anim 
Pract 2014, 44:565–579.
Author  Leslie Sinn
acknowledge the prior contribution of Emily 
D. Levine.
available online
AGGRESSIONSocial interactions
EnvironmentGenetics
PhysiologyLearning
LearningCommunication
Figure 1 .  (continued)  Aggression, Overview—Cats

58 Blackwell’s Five-Minute Veterinary Consult  
AAggression, Overview—Dogs
  BASICS
• Action by one dog directed against another 
organism with the result of limiting, depriving, 
or harming. Aggression refers to any behavior 
along an aggression continuum, from a stare 
to immobility (freeze), growl, snarl, lunge, air 
snap, single bite, multiple bite, multiple 
attacks, and chase and attack.
• Numerous functional types have been 
posited. Here, aggression is classified on the 
basis of (1) affective aggression, (2) predatory 
aggression, and (3) play-related aggression. 
Affective states, such as fear and arousal, and 
motivational factors, such as hunger and 
sexual drive, influence the probability of overt 
aggression, such as biting. Affective aggression 
may be human-directed or dog-directed. 
Within these contexts, there may be 
additional specificity, such as human-directed 
aggression toward unfamiliar persons, or 
human-directed aggression toward familiar 
persons. Often dogs display aggression in a 
single context.
• Human-directed aggression toward familiar 
persons in response to controlling gestures 
was historically called dominance aggression, 
although newer terminology, such as conflict 
aggression, may be used to avoid erroneous 
semantic assumptions inherent in the term 
“dominance.”
• Human- or animal-directed aggression, 
generally toward unfamiliar individuals and 
specific to home location, is called territorial 
aggression. Location is commonly at door of 
entry, but may also involve defense of special 
favored locations such as beds.
• Predatory aggression refers to behaviors 
associated with chasing and hunting prey. It is 
often considered nonaffective and may be 
socially facilitated by other dogs. Predatory 
behaviors may be triggered by movement or 
high-pitched sounds, and may be redirected 
to humans or objects.
• Play-related aggression involves aggressive 
gestures, such as growling and biting, in the 
context of play and is commonly displayed 
toward other dogs or humans. It is often 
initiated by signs of play, such as the play 
bow.
• In all cases, medical factors that might 
contribute to aggression (including pain) 
must be evaluated.
• Affective aggression involves arousal of the 
sympathetic nervous system. Some pathologic 
conditions are associated with an increase in 
aggression because of CNS effects such as 
pain or irritability.
• Abnormalities in the CNS serotonin neuro- 
transmitter system have been implicated in one type of impulsive human-directed 
aggression, colloquially called “rage,” directed 
toward familiar persons and triggered by 
controlling gestures.
• Aggression generally has a learned 
component, whereby dogs learn to use 
aggression to manage distance from fearful 
stimuli or control resources, as this behavior 
is often effective as a distance-increasing 
• Behavior.
• Other, if there is an underlying medical 
etiology.
GENETICS
• In some breeding programs, aggressive 
tendencies and bite styles have been selected 
for (or against).
• Behavioral genetics is an active area of 
research, with several genes identified that 
may be associated with fear and aggression in 
dogs.
• One study in the United States linked 
English springer spaniels that display human- 
directed dominance aggression to one 
breeding sire, implicating a heritable component.
• One study of human-directed dominance 
aggression among English cocker spaniels 
reported that males were more aggressive than 
females, and dogs with solid coat color were 
more aggressive than those with parti coat 
color.
• Reported problem by approximately 30% 
of owners.
• Most common diagnostic category seen by 
board-certified veterinary behaviorists in 
North America.
• According to Centers for Disease Control 
and Prevention, about 4.7 million people 
bitten by dogs each year in United States, 
although this number considered an under- 
estimation as majority of dog bites not 
reported.
• In United States, estimated that one in five 
of those bitten require medical attention for 
dog bite–related injuries.
• Among children and adults, males more 
likely than females to be bitten.
• Based on emergency room data in United 
States, rate of dog bite–related injuries highest 
for children aged 5–9 years.
• In majority of cases, people are bitten by 
dogs that are known to them; this is not the 
case for dog injury–related fatalities.
Worldwide
Species
DogBreed Predispositions
Any breed or breed mix.
Any age, although some forms of aggression 
may arise more commonly at sexual or social 
maturity, while medical causes increasingly 
more likely in adult- or senior-onset aggression.
• Either sex.
• Males—intact or castrated, most commonly 
implicated in cases of human-directed 
“dominance”-type aggression. Intact males 
overrepresented in dog-bite fatalities, but 
covariables, such as owner management, are 
present.
• Females—spayed most commonly implicated 
in aggression to other female dogs in the home. 
In some studies, spayed females less likely than 
males to display human-directed aggression.
SIGNS
• Any dog can display aggression. Many factors, 
including temperament, experience, and 
situational factors, influence propensity to bite.
• Dogs may display behavioral signals as 
warnings, including immobility, growls, snarls, 
or air snaps, which may provide time to avoid 
overt aggression. These signs should not be 
punished, as this might decrease the probability 
of warning signs without affecting the 
underlying risk, or may further intensify the 
aggressive (defensive) response. Instead, the 
animal should be safely removed from the 
situation and the underlying triggers for the 
affective state addressed.
• Variable.
• Basis for risk analysis and details of treat- 
ment program. Important questions: Who/
what was the target? Who was present to 
manage the dog? How severe were the 
resulting injuries? What are the circumstances 
(including location, time) in which aggression 
occurred? Are there any reliable triggers for 
aggressive behavior? Abnormalities in mentation 
or awareness might indicate a medical cause.
• Usually unremarkable.
• Use extreme care when handling aggressive 
dogs.
• A comfortable, well-fitting basket muzzle 
recommended prior to examination of any 
dog with history of human-directed aggression. 
Desensitize and countercondition to muzzle 
application and use. Basket-style muzzles allow 
dogs to pant.
• Abnormalities on physical or neurologic 
examination may suggest organic disease 
process (e.g., neurologic, pain, blindness). 
Dogs can display aggression during preictal, 
ictal, or postictal periods. Dogs with underlying

Canine and Feline, Seventh Edition  59
A
pain typically display defensive (body-
protective) aggression.
CAUSES
• Part of normal range of behavior; strongly 
influenced by individual temperament, 
experience, early socialization (before 12 
weeks), and other variables.
• Harsh handling and confrontational 
responses can escalate aggression and should 
be avoided.
• May be manifestation of organic condition, 
such as hepatic encephalopathy or pain.
• In all cases, evaluate medical causes of 
• Inadequate socialization during canine 
critical period (3–12 weeks).
• T raumatic/fearful/negative experience(s).
• Predisposing environmental conditions—
lack of training, inadequate restraint, harsh 
handling. 
• Inability of owner to safely confine or 
manage the dog in order to prevent future 
incidents. Helpful devices include barrier 
fence, muzzle, collar or head halter, leash.
• Previous aggression/bite history (number of 
incidents, number of bites per incident, 
target, severity of injury); legal citation for 
biting.
• Unpredictability of aggressive behaviors, 
lack of warning signals. 
• Presence of children, elderly people, or 
other humans or animals at high risk living in 
or visiting household.
  DIAGNOSIS
• Thorough medical evaluation should be 
conducted on all cases of aggression. 
• Identify pathologic conditions associated 
with aggression before making purely 
behavioral diagnosis.
• Rule out developmental abnormalities 
(e.g., hepatic shunts), metabolic disorders 
(e.g., hepatic encephalopathy), endocrino-  
pathies (e.g., hypothyroidism, hyperadreno-  
corticism), dermatopathy, neurologic 
conditions (intracranial neoplasm, seizures), 
toxins, inflammatory diseases, cognitive 
dysfunction, acute or chronic pain, and 
iatrogenic causes, such as glucocorticoid 
administration.
• Usually no significant findings unless 
underlying medical etiology.
• Indicated to evaluate dog as candidate for 
behavioral medications.
• Thyroid testing.• Others as indicated by history and physical 
exam.
IMAGING
• May be indicated to identify sources of pain 
or disease.
• MRI or CT—particularly if cerebral 
disease/neoplasia suspected.
• Collection of thorough behavioral history 
and evaluation of medical concerns.
• Postmortem fluorescent antibody test 
indicated for any aggressive dog for which 
rabies is differential diagnosis.
None
  TREATMENT
• Manage any underlying medical 
conditions. 
• Management success—combination of 
multiple modalities: safe environmental 
control, behavior modification to teach 
animals appropriate behavior, and pharma- 
cotherapy.
• Consult veterinarian with experience and 
training in aggression management.
• Euthanasia should be discussed or 
recommended when risk of injury is high. 
Note recommendation in medical record.
• Rehoming aggressive dogs may put those 
involved at liability risk.
A boarding facility able to safely manage the 
dog might be used until a safe management 
plan can be implemented, or until an outcome 
decision can be made.
ACTIVITY
Since frustration and arousal may increase 
incidence of aggression, appropriate and safe 
exercise regime should be incorporated into 
treatment program.
DIET
There is minimal evidence that a low-protein 
diet may reduce territorial aggression in dogs, 
an effect that might be enhanced with trypto- 
phan supplementation.
• Safe practices should dictate all decisions. These 
practices include safe confinement, physical 
barriers, head halters, leash control, muzzle use, 
and supervision by a competent adult.
• Situations that have led to aggression 
in the past should be listed and a specific 
plan developed to avoid these situations 
and associated locations in the future, 
and a long-term management plan developed.• The dog should calmly be removed from 
aggression-provoking situations.
• Safe, nonconfrontational techniques that 
manage resources and use positive reinforce- 
ment to teach the dog appropriate responses 
should be employed.
• Confrontational management techniques, 
such as roll-overs, or even verbal discipline 
increase the probability of a defensive 
aggressive response, may lead to human 
injury, and should be strictly avoided.
• Management (“dominance”) techniques 
including punishment are associated with 
defensive fear responses by the dog and an 
increased risk of human-directed aggression. 
These should be avoided and replaced with 
positive management techniques.
• The client should be advised to consider 
personal and legal liability risks of keeping the 
dog. Human injury, bite-related lawsuits, and 
homeowner’s insurance claims can result from 
canine aggression. Such risk assessment may 
help the client objectively evaluate the situation.
• Euthanasia should be considered if safe 
management cannot be employed, or when 
the risk of injury is high.
Castration of males may reduce the incidence 
of intermale aggression.
• None approved by FDA for treatment of 
• No drug will eliminate probability of 
• Use drugs only when safe management plan 
has been implemented.
• Inform client of extra-label nature of 
medication and risk involved; document in 
medical record; obtain signed informed 
consent.
• Drugs that increase serotonin may be 
helpful to reduce anxiety, arousal, and 
impulsivity.
• T reatment duration—minimum 4 months, 
maximum lifetime.
• See Table 1 for drugs used to facilitate 
management of aggression in combination 
with safe management plan.
• Fluoxetine should be used cautiously in 
cases of seizures.
• Clomipramine contraindicated in cases of 
cardiac conduction disturbances or seizures; 
in one open trial, clomipramine was no more 
effective than control in cases of human-
directed aggression.(continued)  Aggression, Overview—Dogs

60 Blackwell’s Five-Minute Veterinary Consult  
A
Benzodiazepines (e.g., diazepam) may 
contribute to behavioral disinhibition. 
Aggression may increase when dogs lose their 
fear of the repercussions of biting.
Do not use selective serotonin reuptake 
inhibitors (SSRIs) or tricyclic antidepressants 
(TCAs) with monoamine oxidase inhibitors, 
including amitraz and selegiline, or with each 
other because of risk of serotonin syndrome. 
Caution when combining SSRI or TCA with 
any drug that might increase serotonin, 
including trazodone.
• T razodone (4–10 mg/kg PO q12h or PRN) 
may be used with drugs listed in Table 1 to 
reduce anxiety and arousal.
• Clonidine (0.01–0.05 mg/kg PO q12h or 
PRN) may be used with drugs listed in 
Table 1 to reduce anxiety and arousal.
• Natural products that may aid in reducing 
anxiety—l-tryptophan (10 mg/kg PO bid); 
alpha-casozepine (15 mg/kg or higher daily) 
alone or in diet combined with l-tryptophan; 
l-theanine alone (2.5–5 mg/kg bid) or in 
combination with products containing whey 
protein, Phellodendron amurense , and 
Magnolia officinalis ; “calming” probiotic 
supplement; or dog-appeasing pheromone.
  FOLLOW-UP
Weekly to biweekly contact recommended in 
initial phases to guide clients with behavior 
modification plans and medication manage- 
ment.
• To prevent aggressive incidents, avoid all 
situations that have led to aggression in the 
past, using safe confinement, gates, halters, 
collars, leashes, muzzles.• Reduce risk of aggression in young dogs 
(3–12 weeks) with positive socialization 
program; avoid intimidation techniques and 
negative, fear-inducing situations.
• Injury to humans or animals.
• Liability to client, veterinarian.
• In cases of dog-directed aggression, 
although not the intended target, humans 
who interfere are often seriously injured, 
either by accident or by redirected aggression; 
owners should not reach for fighting 
dogs—pull apart with leashes.
• Aggressive dogs are at risk for relinquish- 
ment or euthanasia.
PROGNOSIS
• Aggressive dogs weighing over 18.5 kg are 
at increased risk for behavioral euthanasia.
• Aggressive dogs may be successfully 
managed, but should not be considered 
“cured.”
• Prognosis is case dependent due to risk 
factors and management features of each 
situation.
Onset of aggression in mature dogs suggests 
medical cause; carefully evaluate sensory 
acuity, sources of pain, endocrinopathy, 
cognitive function.
• Dog bites are significant public health risk.
• Rabies is potential cause of aggression.
TCAs and trazodone are contraindicated in 
breeding males and pregnant females.
SYNONYMS
BitingSEE ALSO
• Aggression—Between Dogs in the 
Household.
• Aggression, Food and Resource 
Guarding—Dogs.
• Aggression Toward Children—Dogs.
• Aggression Toward Familiar People—Dogs.
• https://www.avma.org/resources-tools/
pet-owners/dog-bite-prevention
• https://www.cdph.ca.gov/Programs/CID/
DCDC/CDPH%20Document%20Library/
DontLettheDogsBiteActivityBook.pdf
Casey RA, Loftus B, Bolster C, et al. Human 
directed aggression in domestic dogs ( Canis 
familiaris ): occurrence in different contexts 
and risk factors. Appl Anim Behav Sci 
2014, 152:52–63.
deKeuster T, Jung H. Aggression toward 
familiar people and animals. In: Horwitz DF , 
Gloucester: BSAVA, 2009, pp. 182–210.
Landsberg G. Canine aggression. In: Landsberg 
G, Hunthausen W, Ackerman L, eds. 
ed. New York: Saunders/Elsevier, 2013, pp. 
197–326.
home. Vet Clin North Am Small Anim 
Pract 2018, 48:387–402.
Authors  Margaret E. Gruen and Barbara L. 
Sherman
available online  Table 1
Drugs and dosages used to manage canine aggression.
Drug Drug Class Oral Dosage in Dogs Frequency Side Effects—Usually Transient
Fluoxetine SSRI 1.0–2.0 mg/kg q24h Decreased appetite, sleepiness
Paroxetine SSRI 1.0–2.0 mg/kg q24h Constipation
Sertraline SSRI 2.0–4.0 mg/kg q24h Sleepiness
Clomipramine TCA 1.0–3.0 mg/kg q12h Sleepiness, vomitingAggression, Overview—Dogs  (continued)

Canine and Feline, Seventh Edition  61
A Alkaline Hyperphosphatasemia in Dogs
  BASICS
Increase in serum alkaline phosphatase (ALP) 
activity above reference interval.
• ALPs are heterogeneous group of isoen -
zymes that catalyze hydrolysis of organic 
phosphate esters in extracellular space. 
• Membrane-bound enzymes present in liver, 
bone, placenta, intestine, and kidney. • Total 
serum ALP attributed to liver (L-ALP), bone 
(B-ALP), and glucocorticoid-induced (G-ALP) 
isoenzymes; proportion of each isoenzyme 
changes with age in normal dogs. • Serum 
ALP activity increases with cholestatic, 
necroinflammatory, and neoplastic injury; 
many hepatic and nonhepatic causes; affected 
dogs often asymptomatic. • Anticonvulsants 
(phenobarbital, primidone, phenytoin) and 
steroids can induce L-ALP synthesis; steroids, 
inflammation, and chronic disease can induce 
G-ALP synthesis. • ALP has high sensitivity 
but poor specificity for hepatobiliary disease; 
reflects common induction of enzyme synthesis 
due to nonhepatic causes, i.e., “reactive hepato-  
pathy.” • Increased ALP activity with 
concurrent increase in GGT activity increases 
specificity for hepatobiliary disease.
• Multiple organ systems can influence ALP 
synthesis. • Increased ALP activity does not 
cause direct damage to other organ systems.
GENETICS
• Benign familial alkaline hyperphosphata-
semia in Siberian huskies—presumed 
autosomal. • Vacuolar hepatopathy of 
Scottish terriers—breed relationship.
Increased ALP activity is common 
biochemical abnormality in dogs.
• Any age, breed, or sex. • Young dogs, 
<1 year of age—increased B-ALP activity. 
• Siberian huskies and Scottish terriers. 
• Older dogs—conditions causing increased 
L-ALP , G-ALP , and/or B-ALP activity.
SIGNS
• Many dogs with increased ALP activity are 
asymptomatic. • Dogs with hepatic or 
nonhepatic disorders causing increased ALP 
may be asymptomatic or have clinical signs 
related to underlying disorder. • Dogs with 
drug-induced elevations of ALP may have 
clinical signs related to drug side effects.
• Dependent on cause. • Medication history 
important, including exposure to topical/
ocular medications used by humans.Physical Examination Findings
• Highly variable depending on cause; often 
normal. • Hepatomegaly or microhepatica. 
• Jaundice. • Abdominal pain. • Musculo -
skeletal—pendulous abdomen, muscle atrophy, 
lameness, difficulty walking, palpable bony 
swelling. • Dermatologic—alopecia, cutaneous 
hyperpigmentation, comedones, thin skin, 
pyoderma, calcinosis cutis.
CAUSES
• Age and breed (see Signalment). • Drug 
induced. • Bone-related disorders—neopla-
sia, osteomyelitis, hyperparathyroidism 
(primary or secondary), healing fractures. 
• Chronic stress, acute-phase response 
(endogenous cortisol). • Endocrinopathies 
(hyperadrenocorticism, diabetes mellitus, 
hypothyroidism). • Primary hepatobiliary 
disorders. • Extrahepatic disorders—extrahe-
patic biliary obstruction (EHBO), pancreatic/
intestinal/other inflammation, neoplasia. 
• Infection—Leptospirosis, sepsis, viral. 
• Systemic inflammation/infection causing 
ischemic injury/cholestasis. • Hepatic or 
nonhepatic neoplasia (e.g., benign or 
malignant mammary tumors).
• Age (young). • Breed—Siberian husky, 
Scottish terrier. • Breed association to 
conditions causing alkaline hyperphosphata-
semia (e.g., Shetland sheepdog predisposition 
to gallbladder mucocele).
  DIAGNOSIS
Corticosteroids, certain anticonvulsants.
Results
• Severe hemolysis (>500 hemolysis index) 
can falsely elevate ALP . • Lipemia and icterus 
have no significant effect on ALP .
• Thrombocytosis possible with hyperadreno -
corticism and pancreatic, gastrointestinal 
disease. • Thrombocytopenia possible with 
leptospirosis, hepatic failure, neoplasia. 
• Leukocytosis or leukopenia with left shift, 
monocytosis with sepsis, systemic 
inflammation. • Stress leukogram with 
hyperadrenocorticism. • Concurrent elevation 
of other liver enzyme activities including 
alanine aminotransferase (ALT), aspartate 
aminotransferase (AST), and/or gamma 
glutamyltransferase (GGT), depending on 
underlying cause. • ± markers of hepatic 
synthetic dysfunction (hypoalbuminemia, 
hypoglycemia, hypocholesterolemia, 
decreased blood urea nitrogen [BUN]); 
many primary hepatic disorders. • Hyperbilirubinemia in EHBO, end-stage 
chronic hepatopathies, acute hepatic 
toxicities, infections. • Hypercholesterolemia 
with many causes of cholestasis, 
endocrinopathies. • Urinalysis—proteinuria 
with hyperadrenocorticism, other liver 
disorders; dilute urine, bacteriuria, pyuria 
with endocrinopathies; glucosuria with 
diabetes mellitus, copper-associated hepatopathy; 
ammonium biurate crystalluria with 
portosystemic vascular anomaly (PSVA; 
young dogs). • Conditions with often sole 
increase in serum ALP include idiopathic 
vacuolar hepatopathy, hepatic nodular hyper- 
plasia, drug-induction breed-related disorders, 
some hepatic neoplasias, sudden acquired 
retinal degeneration (SARDS). 
• Hyperphosphatemia, hypercalcemia (young 
growing dogs, usually mild). • Hyperglycemia—  
mild with hyperadreno  corticism. 
• Azotemia—prerenal or renal with 
pancreatitis, pyelonephritis, Leptospirosis.
• Serum bile acids; redundant test if 
hepatic hyperbilirubinemia. • Testing for 
endocrine disorders—hypothyroidism or 
hyperadrenocorticism based on clinical 
signs, physical exam findings, and 
associated laboratory abnormalities. 
• Infectious disease testing—leptospirosis 
PCR, microagglutination test (MAT), 
immunoglobulin (Ig) M; urine, bile 
cultures; tick-borne disease screening. 
• Blood pressure measurement. • Urine 
protein qualitative; quantitative with 
protein; creatinine if inactive sediment and 
culture negative.
IMAGING
• Radiographs—for liver most useful for 
hepatomegaly, microhepatica; nonhepatic 
findings may also be identified (pancreatitis, 
ascites, cystoliths, pyometra, pleural effusion). 
• Sonographic evaluation for hepatic 
parenchymal abnormalities (hyper- or 
hypoechoic nodules, heterogeneity, hyper- or 
hypoechoic hepatic echogenicity; changes in 
echodensity, echotexture; microhepatica, 
hepatomegaly, hepatic masses), biliary tract 
(gallbladder mucocele, gallbladder wall 
abnormalities, cholelithiasis, choledochitis, 
biliary tract neoplasia), pancreas, adrenal 
enlargement, neoplasia. • Abdominal CT ± 
angiography may be useful if suspicion of 
pancreatitis, gallbladder disease, or hepatic 
vascular disorders.
• Hepatic fine-needle aspirate (FNA) for 
cytology; caution as cytologic and histologic 
agreement may be as low as 30%; cytology is 
not diagnostic for many hepatobiliary 
conditions. • FNA of liver tends to agree 
with histology in cases of vacuolar hepato- 
pathy, hepatic lipidosis, and some neoplasias 
(e.g., lymphoma). • If primary hepatobiliary

62 Blackwell’s Five-Minute Veterinary Consult  
A
disease suspected after elimination of other 
causes, hepatic biopsy may be warranted; 
biopsy at least three liver lobes; laparoscopic 
or wedge samples preferred; Tru-Cut® needle 
biopsy may be too small, use 14–16G needle.
Variable depending on cause; see specific 
chapters for pathologic findings.
  TREATMENT
• Dictated by underlying disorder. 
• Asymptomatic dogs often do not require 
any specific treatment.
Variable as above.
ACTIVITY
Alteration of activity typically unnecessary.
DIET
• Dietary alteration unnecessary in most 
cases. • Dietary fat restriction in some cases 
(pancreatitis, hypertriglyceridemia, obesity, 
chronic EHBO). • Commercial liver diets 
rarely  indicated (see Portosystemic Vascular 
Anomaly, Congenital; Hepatic Encephalopathy).
• Dictated by underlying disorder. • Clients 
with asymptomatic dogs should be counseled 
on potential for subsequent development of 
endocrine disease, neoplasia (Scottish 
terriers), other causes. • Liver biopsy 
necessary for definitive diagnosis if other 
underlying causes are ruled out and/or if ALP 
value continues to elevate; rarely pursued 
initially in asymptomatic dogs without other 
underlying disorder.
• Refractory hypotension is common peri- 
and postoperative complication in dogs with 
obstructive cholestasis (see EHBO). • Dogs 
with end-stage hepatic disease (cirrhosis) may 
have alterations of coagulation and/or higher 
anesthetic risk.  MEDICATIONS
• Specific for underlying cause. • Certain 
drugs/supplements have general hepatobiliary 
protective effects; see Hepatosupportive 
Therapies.
Depending on cause, drugs requiring hepatic 
metabolism or capable of causing hepatotoxicity 
should be limited or avoided when possible.
Drugs known to induce elevation of ALP may 
confuse monitoring of underlying condition.
  FOLLOW-UP
• Dependent on the underlying cause. 
• Suspected benign causes of ALP elevation 
can be monitored for elevations in other serum 
liver enzyme activities, further elevation in 
ALP , and/or synthetic hepatic function tests.
• Dependent on underlying cause. 
• Increased ALP activity for which underlying 
cause cannot be found after complete diagnostic 
evaluation may be benign.
Elevation of other serum liver enzymes, 
hyperbilirubinemia, alterations in hepatic 
synthetic function tests.
Young dogs (see Signalment).
Leptospirosis has high zoonotic potential; see 
Leptospirosis.
Placental ALP can increase in late-term 
pregnant cats; not reported in dogs.SYNONYMS
• Elevated ALP . • Serum alkaline phosphatase 
(SAP).
SEE ALSO
• Bile Duct Obstruction (Extrahepatic).
• Cholangitis/Cholangiohepatitis Syndrome.
• Cholecystitis and Choledochitis.
• Cholelithiasis.
• Copper Associated Hepatology.
• Glycogen-Type Vacuolar Hepatopathy
• Hepatic Failure, Acute.
• Hepatic Nodular Hyperplasia and Dysplastic 
Hyperplasia.
• Hepatitis, Chronic.
• Hyperadrenocorticism (Cushing’s Syndrome)—  
Dogs.
• ALP = alkaline phosphatase.
• B-ALP = bone isoform.
• G-ALP = glucocorticoid isoform.
• EHBO = extrahepatic biliary obstruction.
• FNA = fine-needle aspirate.
• GGT = gamma glutamyltransferase.
• Ig = immunoglobulin.
• L-ALP = liver isoform.
• MAT = microagglutination test.
• PSVA = portosystemic vascular anomaly.
• SAP = serum alkaline phosphatase.
• SARDS = sudden acquired retinal 
degeneration.
Cortright CC, Center SA, Randolph JF , et al. 
Clinical features of progressive vacuolar 
hepatopathy in Scottish Terriers with and 
without hepatocellular carcinoma: 114 cases 
(1980–2013). J Vet Intern Med 2014, 
245:797–788.
Lidbury JA, Steiner JM. Diagnostic 
evaluation of the liver. In: Washabau RJ, 
Day MJ, eds., Canine and Feline 
Gastroenterology. St. Louis, MO: Elsevier, 
2013, pp. 863–875.
Author  Sara A. Wennogle
Consulting Editor  Kate HolanAlkaline Hyperphosphatasemia in Dogs  (continued)

Canine and Feline, Seventh Edition  63
A Alkalosis, Metabolic
  BASICS
A process in the body that leads to an increase 
in pH above the reference interval. An increase 
in blood pH is specifically termed alkalemia. 
Associated with an increase in plasma 
bicarbonate concentration (HCO–
3; dogs, 
>24 mEq/L; cats, >22 mEq/L) and base 
excess (BE; >4 mmol/L) with a compensatory 
increase in carbon dioxide tension (PCO2).
• Metabolic alkalosis may develop from either 
a gain of bicarbonate  or a loss of acid : 
◦ Bicarbonate gain  subsequent to: contraction 
alkalosis due to free water deficit; iatrogenic 
administration of alkalinizing therapy (e.g., 
NaHCO–
3); metabolism of organic ions 
(lactate, citrate, acetate, and ketones); 
hypokalemia; and renal ammoniagenesis. 
◦ Acid loss  subsequent to: gastric or renal acid 
loss (loop or thiazide diuretic); mineralocorti-
coid excess; presence of nonreabsorbable 
anions; decreased weak acids (hypoalbumine-
mia, hypophosphatemia). ◦ Renal HCO–
3 
excretion very efficient in eliminating an 
excess HCO–
3 load, but hindered by decreased 
effective circulating volume; hypokalemia, 
hypochloremia, and hyperaldosteronism; 
metabolic alkalosis persists only if renal 
excretion of HCO–
3 is impaired, which 
primarily occurs from continued high rate of 
alkali administration, or some stimulus for 
kidneys to retain Na+ in presence of a relative 
Cl– deficit. • Hypochloremic (corrected)  
metabolic alkalosis results from loss of fluid 
rich in Cl– and hydrogen ion (H+), primarily 
from alimentary tract or kidneys; loss of Cl– 
and H+ associated with increase in plasma 
HCO–
3 concentration; with Cl– loss and 
volume depletion, kidneys reabsorb Na+ with 
HCO–
3 instead of Cl–, perpetuating metabolic 
alkalosis. Hypochloremic alkalosis divided 
into chloride-responsive  and chloride-resistant : 
◦ Chloride-responsive  results primarily from 
loss of Cl– rich fluid and characterized by 
decreased extracellular fluid volume, hypo- 
chloremia, and low urinary Cl– concentration; 
this type of alkalosis responds to 
administration of chloride salt. ◦ Chloride-
resistant  characterized by excessive mineralo-
corticoid leading to increased effective 
circulating volume and is not responsive to 
chloride salt. • Hypokalemia  may contribute 
to metabolic alkalosis by shifting H+ intra- 
cellularly; stimulating apical H+/K+ ATPase 
in collecting duct; stimulating renal 
ammoniagenesis; impairing Cl– reabsorption 
in distal nephron; and reducing glomerular 
filtration rate (GFR), which decreases filtered 
load of HCO–
3 and, in presence of volume 
depletion, impairs renal excretion of excess 
HCO–
3. • Hypoalbuminemic  alkalosis is due to decrease in plasma albumin concentration; 
plasma albumin is a weak acid. • Compensatory  
metabolic alkalosis occurs in response to 
respiratory acidosis; this is associated with low 
pH and increased PCO2.
• Nervous—muscle twitching and seizures 
occur rarely in dogs. Metabolic alkalosis and 
associated hypokalemia may precipitate hepatic 
encephalopathy in patients with liver failure. 
• Urinary—kidneys rapidly and effectively 
excrete excessive alkali. In patients with 
Cl– deficiency and volume depletion, kidneys 
cannot excrete excess alkali. Therefore, 
metabolic alkalosis is maintained. In these 
patients, Cl– administration is required for 
renal compensation to occur. Volume 
expansion will hasten compensation. Patients 
with mineralocorticoid excess have excessive 
Cl– loss. Therefore, Cl– administration does 
not lead to hyperchloremia and correction of 
metabolic alkalosis (so-called chloride-resist-
ant metabolic alkalosis). • Respiratory—low 
[H+] (increased pH) decreases alveolar 
ventilation. Hypoventilation increases PCO2 
and helps offset the effects of high plasma 
HCO–
3 on pH. In dogs, for each 1 mEq/L 
increase in plasma HCO–
3 there is an expected 
increase of approximately 0.7 mmHg in 
PCO2. Limited data available for cats, but 
degree of respiratory compensation appears to 
be similar.
SIGNS
• Administration of loop diuretics 
(e.g., furosemide) or thiazides. • Vomiting.
• Signs related to underlying disease or 
accompanying potassium depletion 
(e.g., weakness, cardiac arrhythmias, ileus). 
• Muscle twitching caused by low ionized 
calcium concentration. • Dehydration in 
volume-depleted patients. • Muscle twitching 
and seizures in patients with neurologic 
involvement (rare).
CAUSES
• Chloride-responsive —gastrointestinal losses 
(e.g., gastric vomiting, nasogastric tube 
suctioning); renal losses (diuretic therapy); 
and rapid correction of chronic hypercapnia 
(respiratory acidosis). • Chloride-resistant —
hyperadrenocorticism and primary hyperaldo-  
steronism. • Oral administration of 
alkalinizing agents —sodium bicarbonate or 
other organic anions with Na+ (e.g., lactate, 
acetate, gluconate); administration of 
cation-exchange resin with nonabsorbable 
alkali (e.g., phosphorus binders). 
• Hypoalbuminemia —liver disease, protein-
losing nephropathy, protein-losing enteropathy. 
• Free water deficit —diabetes insipidus; water deprivation; postobstructive diuresis; 
polyuric renal failure. • Hypokalemia .
• Administration of loop or thiazide diuretics. 
• Vomiting. • Stomach drainage. • Diseases 
associated with hypoalbuminemia (e.g., 
protein-losing nephropathy, liver failure).
  DIAGNOSIS
High plasma HCO–
3 and hypochloremia may 
also occur in animals compensating for chronic 
respiratory acidosis, in which PCO2 is high 
and pH is low despite high HCO–
3 and low 
Cl– concentration; blood gas determination is 
required to differentiate.
None
Results
decreases pH, PCO2, and HCO–
3. • Blood 
samples stored at room temperature for more 
than 15 minutes have low pH because of 
increased PCO2. • Exposure to room air 
decreases PCO2. • Venous samples may have 
pH 0.5–1 unit lower and PCO2 5–10 mmHg 
higher than arterial sample.
Yes
• High total CO2 (total CO2 in samples 
handled aerobically closely approximates 
HCO–
3). • Low blood ionized calcium 
concentration. • Serum electrolyte 
abnormalities vary with underlying cause. 
• Hypochloremia—consider hypochloremic 
metabolic alkalosis, the most common reason 
for metabolic alkalosis in dogs and cats, which 
usually results from diuretic administration or 
vomiting of stomach contents. • High Na+ but 
normal Cl– concentration—consider chloride-
resistant metabolic alkalosis (e.g., hyperadreno-  
corticism or primary hyperaldosteronism) or 
administration of alkali. • Hypoalbuminemia—  
consider hypoalbuminemic metabolic alkalosis 
(e.g., liver failure, protein-losing enteropathy, 
and protein-losing nephropathy). In vitro, 
a 1 g/dL decrease in albumin concentration is 
associated with an increase in pH of 0.093 in 
cats and 0.047 in dogs. • Hypokalemia—likely 
results from intracellular potassium shifting 
due to metabolic alkalosis or underlying 
problem (e.g., vomiting of stomach contents or 
loop diuretic administration). • Urinary

HCO–
loop diuretic administration). • Urinary 
Cl– concentrations—chloride-responsive 
metabolic alkalosis characterized by urine 
Cl– concentrations <10 mEq/L, whereas

64 Blackwell’s Five-Minute Veterinary Consult  
A
chloride-resistant metabolic alkalosis associated 
with urine Cl– concentrations >20 mEq/L.
Blood gas analysis reveals high HCO–
3, PCO2, 
pH, and BE. Unlike HCO3-, BE is inde-
pendent of changes in metabolic acid-base 
status, and is thus more reliable measure of 
metabolic acid-base changes.
IMAGING
None
• Blood pressure—combination of hyperten-
sion, hypernatremia, and hypokalemia with 
metabolic alkalosis may indicate presence of 
hyperaldosteronism. • Diagnostic testing for 
hyperadrenocorticism or primary hyperaldo-
steronism (e.g., plasma renin activity and 
aldosterone concentration).
  TREATMENT
phenomena; diagnosis and treatment of 
underlying disease process are essential to 
successful resolution of acid-base disorders.  
• Severe alkalemia is uncommon, but may be 
life-threatening. Patients with chronic 
respiratory disease and respiratory alkalosis 
are at risk of developing severe alkalemia if 
they start vomiting or receive diuretics. 
metabolic alkalosis. • Chloride-responsive —
fluid of choice for patients with volume 
depletion is 0.9% saline or balanced isotonic 
replacement fluid supplemented with KCl; 
patients with hypokalemia may require large 
amounts of KCl (see Hypokalemia).  
• Chloride-resistant  metabolic alkalosis can 
only be corrected by resolution of underlying 
disease; metabolic alkalosis usually mild in 
these patients. • If metabolic alkalosis 
associated with hypokalemia and total body 
potassium deficits, correcting deficit with KCl 
is particularly effective way to reverse 
alkalosis.
Supportive care to maintain normal hydration, 
plasma volume, and adequate nutrition.
Hypochloremic Alkalosis
• If chloride-responsive alkalosis occurs 
during edematous state (e.g., congestive heart failure), oral administration of compounds 
containing Cl– without Na+ is recommended 
to correct alkalosis; if diuresis needed due to 
volume overload, carbonic anhydrase 
inhibitor (e.g., acetazolamide) or potassium-
sparing diuretic (e.g., spironolactone, 
amiloride) can be used to correct alkalosis. 
• H2-blocking agents such as famotidine 
decrease gastric acid secretion and may be 
considered as adjunctive therapy if gastric 
losses are ongoing. • Antiemetics may help 
prevent further gastric acid loss.
Hypoalbuminemic Alkalosis
• T reatment for hypoalbuminemic alkalosis 
should be directed at underlying cause and 
decreased colloid oncotic pressure. • Enteral 
nutrition will facilitate endogenous albumin 
production. • Consider species-specific 
plasma or albumin (e.g., canine albumin) 
therapy.
• Avoid chloride-free fluids—they may 
correct volume depletion, but will not correct 
hypochloremic alkalosis. • Avoid using salts 
of potassium without Cl– (e.g., potassium 
phosphate)—potassium will be excreted in 
urine and will correct neither alkalosis nor 
potassium deficit.
Do not use distal-acting, potassium-sparing 
diuretics (e.g., spironolactone) in volume-
depleted patients.
None
None
  FOLLOW-UP
Acid-base status—frequency dictated by 
underlying disease and patient response to 
• Hypokalemia. • Neurologic signs.
• Hypokalemia. • Hypochloremia.
None
N/ASYNONYMS
• Nonrespiratory alkalosis. • Chloride-
responsive metabolic alkalosis—metabolic 
alkalosis that responds to Cl– administration. 
• Chloride-resistant alkalosis—metabolic 
alkalosis secondary to increased mineralo -
corticoid activity that does not respond to 
Cl– administration. • Hypochloremic 
alkalosis—metabolic alkalosis caused by low 
Cl– concentration. • Hypoalbuminemic 
albumin concentration. • Concentration 
alkalosis—metabolic alkalosis resulting from 
decreased free water in plasma. • Contraction 
alkalosis—metabolic alkalosis formerly 
attributed to volume contraction, but now 
known to be caused by Cl–  depletion; volume 
depletion is common but not essential feature.
SEE ALSO 
• Hypochloremia.
• Hypokalemia.
• GFR = glomerular filtration rate.
• HCO–
3 = bicarbonate.
de Morais HA. Chloride ion in small animal 
practice: the forgotten ion. J Vet Emerg Crit 
Care 1992, 2:11–24.
Saunders, 2012, pp, pp. 316–330.
St. Louis, MO: Saunders, 2012, pp. 302–315.
Silverstein DC, Hopper K, eds. Small 
Robinson EP , Hardy RM. Clinical signs, 
diagnosis, and treatment of alkalemia in 
dogs: 20 cases (1982–1984). J Am Vet Med 
Assoc 1988, 192:943–949.
Authors  Helio S. Autran de Morais and 
Stephen P . DiBartola
acknowledge the prior contribution of Lee E. 
Palmer.Alkalosis, Metabolic  (continued)

Canine and Feline, Seventh Edition  65
A Alopecia—Cats
  BASICS
Common problem, seen as abnormal lack of 
hair coat.
Specific and unique for each cause.
• Skin/exocrine.
• Age, breed, or sex predilections specific to 
each condition.
• Neoplastic- and paraneoplastic-associated 
alopecias generally recognized in older cats.
SIGNS
Depends on specific diagnosis. Knowing 
whether cat is pruritic is a very important part 
of workup for alopecia.
CAUSES
• Infectious—dermatophytosis, parasitic 
(mites, fleas), superficial and deep 
bacterial infections, viral: herpesvirus, 
papillomaviral plaques, feline immuno-  
deficiency virus (FIV)– and feline leukemia 
virus (FeLV)–associated giant cell 
dermatosis.
• Hypersensitivity—atopy/allergy, oral 
medication reaction, topical medication 
reaction.
• Disorders of hair follicle cycling—telogen 
effluvium, Cushing’s (iatrogenic and hyper- 
adrenocorticism), hypothyroidism 
(iatrogenic).
• Congenital—hair follicle dystrophy, 
alopecia universalis (normal in sphynx cats), 
feline hypotrichosis (Siamese and Rex cats), 
pinnal hypotrichosis.
• Environmental—solar damage, burns, 
frostbite, scarring.
• Ischemic—post matting alopecia, post 
traumatic.
• Autoimmune—alopecia areata, pemphigus 
foliaceus.
• Neoplastic—epitheliotropic lymphoma, 
mastocytosis, squamous cell carcinoma 
in situ.
• Manifestation of internal disease—
sebaceous adenitis (thymoma-associated 
exfoliative dermatitis), paraneoplastic 
alopecia, mural lymphocytic folliculitis, 
hyperthyroidism, hyperadrenocorticism, 
diabetes.
• Psychogenic—compulsive disorder.
FeLV/FIV—reported risk for demodicosis 
(not all cases associated with viral 
infection).  DIAGNOSIS
• Parasites
 ◦Mites— Demodex gatoi , cheyletiella , 
notoedres  are often pruritic and scaly; 
Demodex cati  cause hair loss with minimal 
inflammatory change in many cases.
 ◦Fleas can cause alopecia if patient is 
hypersensitive and pruritic; severe on caudal 
dorsum, abdomen, and around ears.
 ◦Tick attachment sites can cause alopecic 
granuloma.
• Bacterial:
 ◦Alopecia secondary to deep bacterial 
 ◦Superficial bacterial infections secondary 
to underlying cause.
• Viral:
 ◦Herpesvirus can cause neuralgia, pruritus, 
alopecia, and ulcerated eosinophilic skin 
lesions, most commonly on the face.
 ◦FIV- and FeLV-associated giant cell 
 ◦Papillomaviral plaques in older cats may 
transform to squamous cell carcinoma.
Hypersensitivities
• Food, flea bites, or environmental allergens 
(atopy)—ears, face, and abdomen are most 
affected.
• Oral medication reactions—severe facial 
pruritus caused by methimazole: symptoms 
resolve when medication discontinued.
• Topical parasite preventives—rare cause of 
alopecia at site of application; usually temporary.
Disorders of Hair Follicle Cycling
• Telogen effluvium:
 ◦Caused by severe stressful situation or 
hormonal change such as anesthesia/
surgery, parturition, severe illness, drugs.
 ◦Sudden onset of large symmetric areas of 
hair thinning or alopecia.
 ◦Hair regrows over weeks.
• Cushing’s syndrome:
 ◦Long-term (months) corticosteroid 
administration, oral or injectable.
 ◦Megestrol acetate administration.
 ◦Hyperadrenocorticism from adrenal 
tumor or pituitary tumor.
 ◦Causes symmetric alopecic and atrophic/
thin skin, sometimes skin fragility/tearing, 
ear tips droop.
• Hypothyroidism—iatrogenic is most 
common cause, due to treatment of hyper- 
thyroidism.
Congenital
• Hair follicle dystrophy/sebaceous gland 
dystrophy can cause thin hair diffusely or 
waxy accumulations on the hairs.• Alopecia universalis (normal in sphynx 
cats):
 ◦Hereditary, complete absence of primary 
hairs; decreased secondary hairs.
 ◦Sebaceous and apocrine ducts open onto 
skin surface; oily feel to skin.
 ◦Wrinkled foreheads; gold eyes; no 
whiskers; downy fur on paws, tip of tail, 
and scrotum.
 ◦Comedones with or without secondary 
folliculitis.
• Feline hypotrichosis:
 ◦Siamese and Devon Rex cats (autosomal 
recessive alopecia).
 ◦Poorly developed primary telogen hair 
follicles.
 ◦Born with normal coat, which becomes 
thin and sparse as young adult.
Environmental
• Solar damage—skin can be damaged 
with prolonged sun exposure; most 
common in outdoor light-colored cats. 
Areas with thin hair most affected: ears, 
eyes, and nose; early signs alopecia, scaling, 
and erythema; can transform to squamous 
cell carcinoma.
• Burns/frostbite—burns are location 
dependent’ sometimes have a drip-like 
pattern if caused by hot liquid; affect pressure 
points if due to heating pad. Third-degree 
burns will have permanent scars. Frostbite 
commonly affects ear tips and causes alopecia 
and necrosis.
• Scarring is loss of hair follicles and usually 
pigment from area of skin.
Ischemic
• Post matting/traction—caused by loss of 
blood supply to hair follicle due to tight 
prolonged matting or pulling of hair; usually 
hair regrows with time.
• Post traumatic—rare, alopecia with little 
inflammation can be seen with injuries where 
nerve or blood supply interrupted to the skin.
Autoimmune
• Alopecia areata—rare, alopecia with little 
outward inflammation, most common on 
face and head.
• Pemphigus foliaceus—crusting and alopecia 
on ears, sometimes nose, feet, and other areas; 
pruritus variable.
Neoplastic
• Epitheliotropic lymphoma—scaly alopecia, 
eventually plaques and nodules.
• Squamous cell carcinoma in situ—papillo- 
maviral plaques: in older cats, scaly, crusty, 
often pigmented, multifocal, sometimes 
pruritic.
Manifestation of Internal Disease
• Thymoma-associated exfoliative dermatitis:
 ◦Nonpruritic dramatic scaling dermatitis 
that starts on head and neck.
 ◦Surgical removal of thymoma resolves 
dermatitis over 4–5 months.

66 Blackwell’s Five-Minute Veterinary Consult  
A
• Paraneoplastic alopecia:
 ◦Most cases associated with pancreatic 
adenocarcinomas, bile duct carcinomas.
 ◦Nonpruritic alopecia has acute onset, 
progresses rapidly; bilaterally symmetric, 
ventrally distributed (also located along 
bridge of nose and periocular); hair epilates 
easily; dry fissuring footpads; skin often 
thin and hypotonic; rapid weight loss.
• Mural lymphocytic folliculitis—sometimes 
paraneoplastic: alopecia of face, eyelids, 
muzzle; skin has thick, waxy feel; histologic 
lymphocytic invasion of follicular outer root 
sheath and epidermis.
• Hyperthyroidism—alopecia due to 
self-barbering; can see weight loss as well.
• Hyperadrenocorticism—symmetric, 
nonpruritic; older cat if natural, any age if 
iatrogenic; can have severe skin fragility.
• Diabetes—unkempt and unhealthy coat, 
skin infections.
Psychogenic
Although anxiety may make overgrooming 
worse from any underlying condition, a pure 
compulsive disorder is very rare; all other 
causes of alopecia must be ruled out prior to 
considering.
Abnormalities may be noted with diabetes 
mellitus, hyperadrenocorticism, and 
hyperthyroidism.
• FeLV and FIV—risk factors for demodico-
sis and other infections.
• Thyroid hormones—document hyperthy-
roidism/hypothyroidism.
IMAGING
• Abdominal ultrasound—assess adrenals in 
hyperadrenocorticism and look for neoplasia 
in animals with paraneoplastic syndrome.
• Chest radiographs/ultrasound to rule out 
thymoma.
• CT scan—look for pituitary or other 
neoplasia tumors in animals with hyperadreno-  
corticism.
• Skin scrapes.
• Dermatophyte culture.
• Parasite treatment trials, since negative skin 
scrapes do not rule out all parasites.
• Skin biopsy.
• Shirts/collar to prove self-trauma if pruritus 
is questioned.
• Food elimination trials if parasites and 
dermatophytes are ruled out.
• Intradermal allergy testing.  TREATMENT
• See specific chapters for full list of 
medications, doses, and other therapies.
• If pet is compliant, shampoo and topical 
therapy may relieve secondary problems such 
as hyperkeratosis, crusting, or secondary 
bacterial infections.
• Demodicosis—fluralaner topically as per 
label every 3 months; lime sulfur dips at 
weekly intervals for six dips; other mites and 
fleas also respond to appropriate topical or 
oral treatments.
• Allergic dermatitis—antihistamines only 
rarely helpful; novel restricted-ingredient diet; 
corticosteroids; cyclosporine (5–7 mg/kg/day 
initially); allergen-specific immunotherapy; 
ectoparasite control.
• Hyperthyroidism—methimazole, 
thyroidectomy, or radioactive iodine 
therapy.
• Diabetes mellitus—regulation of glucose 
levels (insulin, weight loss, diet).
• Hyperadrenocorticism—discontinue 
glucocorticoids if iatrogenic; if natural, 
trilostane, mitotane, and surgery are options.
• Paraneoplastic alopecia—surgical excision 
of neoplasia; but neoplasia often fatal.
• Epitheliotropic lymphoma—corticoster-
oids, lomustine.
• Sebaceous adenitis—surgical removal of 
thymoma, corticosteroids, cyclosporine.
• Squamous cell carcinoma in situ—surgical 
excision, retinoids (topical and oral), topical 
imiquimod cream.
Toxicity with griseofulvin and itraconazole 
(see Dermatophytosis).
  FOLLOW-UP
Determined by specific diagnosis.
Determined by specific diagnosis.EXPECTED COURSE AND PROGNOSIS
• Dermatophytosis—can cause skin lesions in 
humans.
• Cheyletiellosis—can cause irritation in 
humans.
SEE ALSO
• Cheyletiellosis.
• Diabetes Mellitus Without Complication— 
Cats.
• Feline Paraneoplastic Alopecia.
• Flea Bite Hypersensitivity and Flea Control.
Cats.
• Hyperthyroidism.
• Lymphoma, Cutaneous Epitheliotropic.
• Pemphigus.
• Sebaceous Adenitis, Granulomatous.
• Squamous Cell Carcinoma, Skin.
• Thymoma.
Backel K, Cain C. Skin as a marker of general 
feline health: cutaneous manifestations of 
infectious disease. J Feline Med Surg, 2017, 
19(11):1149–1165.
Diesel A. Cutaneous hypersensitivity derma -
toses in the feline patient: a review of allergic 
skin disease in cats. Vet Sci, 2017, 4(2):25.
Mecklenburg L, Linek M, Tobin DJ. Hair 
Loss Disorders in Domestic Animals. 
Chichester: Wiley, 2009.
Vogelnest LJ. Skin as a marker of general 
systemic disease. J Feline Med Surg, 2017, 
19(9):948–960.
Resnick
available onlineAlopecia—Cats  (continued)

Canine and Feline, Seventh Edition  67
A Alopecia—Dogs
  BASICS
• Common disorder.
• Characterized by complete or partial loss of 
hair in areas where it is normally present.
• May be associated with multiple causes, be 
the primary problem, or be secondary to an 
underlying cause.
• Multiple causes.
• Represents removal of hair or disruption in 
the growth of the hair from hypersensitivity, 
infection, genetic abnormality, trauma, 
immunologic attack, mechanical “plugging,” 
endocrine abnormalities, neoplasia, drug 
reaction, and/or blockage of receptor sites for 
stimulation of hair growth cycle.
Age, breed, and sex predilections are specific 
to each cause listed.
SIGNS
• May be acute in onset or slowly progressive.
• Multifocal patches of alopecia are associated 
with folliculitis caused by demodicosis, 
dermatophytosis, or, most commonly, 
staphylococcus infection.
• Large, more diffuse areas of alopecia may 
indicate follicular dysplasia or metabolic 
• Pattern and degree of hair loss, along with 
presence of pruritus, are important for 
establishing differential diagnoses.
CAUSES
(mites, fleas), superficial and deep bacterial 
• Hypersensitivity/reaction—atopy/allergy, 
oral medication reaction, topical medication 
reaction.
(iatrogenic), alopecia X, seasonal flank 
alopecia.
• Congenital—hair follicle dystrophy.
• Ischemic—post-matting alopecia, barrette 
or rubber band too tight, dermatomyositis, 
post vaccine, vasculitis.
foliaceus, sebaceous adenitis, vasculitis.
• Neoplastic—epitheliotropic lymphoma.
• Manifestation of internal disease—hypo- 
thyroidism, hyperadrenocorticism.RISK FACTORS
Chronic corticosteroid use causes hair cycle 
arrest with other signs of iatrogenic Cushing’s.
  DIAGNOSIS
Multifocal Alopecia
• Demodicosis—partial to complete alopecia 
with erythema, comedones, and mild scaling; 
lesions may become inflamed and crusted.
• Dermatophytosis—partial to complete 
alopecia with scaling, with or without 
erythema, not usually ring-like.
• Staphylococcal folliculitis—circular patterns 
of alopecia with epidermal collarettes, erythema, 
crusting, and hyperpigmented macules.
• Injection/topical medication reactions—
inflammation with alopecia and/or cutaneous 
atrophy from scarring.
• Rabies vaccine vasculitis—well-demarcated 
patch of alopecia observed 1–3 months post 
vaccination. Small-breed dogs more predisposed.
• Alopecia areata—noninflammatory areas of 
complete alopecia.
• Sebaceous adenitis of short-coated breeds— 
annular to polycyclic areas of alopecia and 
scaling.
Symmetric Alopecia
• Hyperadrenocorticism—truncal alopecia 
associated with atrophic skin, comedones, 
and pyoderma, as well as other systemic signs.
• Hypothyroidism—thinning of truncal 
haircoat; generalized alopecia is uncommon 
presentation; alopecic “rat” tail.
• Noninflammatory alopecia (alopecia 
X)—symmetric truncal alopecia associated 
with hyperpigmentation; alopecia often starts 
along collar area of neck; Pomeranian, chow 
chow, Akita, Samoyed, Keeshonden, Alaskan 
Malamute, and Siberian husky.
• Hyperestrogenism (females)—symmetric 
alopecia of flanks and perineal and inguinal 
regions with enlarged vulva and mammary 
glands; may also be associated with exogenous 
hormone exposure.
• Male feminization from Sertoli cell tumor—  
alopecia of perineum and genital region with 
gynecomastia.
• Seasonal/cyclic/flank alopecia—common, 
serpiginous flank alopecia with hyperpig- 
mentation; boxer, English bulldog, Airedale 
terrier.
• Color mutant/dilution alopecia—brittle or 
coarse hair, thinning of blue or fawn-colored 
hair coat, and secondary folliculitis; other 
colors of hair normal.
• Follicular dysplasia—slowly progressive 
alopecia affecting one color of hair.
• Anagen defluxion and telogen defluxion—
acute onset of alopecia due to stressful event.• Epitheliotropic lymphoma—diffuse, 
generalized truncal alopecia with scaling and 
intense erythema; later nodule and plaque 
formation.
• Pemphigus foliaceus—hair loss associated 
with scale and crust formation.
• Sebaceous adenitis—hair straightening, 
thinning, with dry hyperkeratosis; standard 
poodles and crosses, Havanese, other breeds.
• Allergic dermatitis with secondary 
infections and self-trauma due to pruritus.
Specific Locations
• Pinnal alopecia/pattern baldness—
miniaturization of hairs and progressive 
alopecia; dachshund, greyhound, American 
water spaniel, Portuguese water spaniel, 
Boston terrier, Manchester terrier, whippet, 
Italian greyhound, Chihuahua.
• Pinnal alopecia with crusting or necrosis—
consider vasculitis, which can have many 
triggers.
• T raction alopecia—hair loss secondary to 
having barrettes or rubber bands applied to 
the hair, or prolonged tight matting of the 
hair.
• Post-clipping alopecia—failure to regrow 
after clipping associated with slow or arrested 
hair cycle.
• Melanoderma (alopecia of Yorkshire 
terriers)—symmetric alopecia of pinnae, 
bridge of nose, tail, and feet.
• Seasonal/cyclic/canine flank alopecia—
terrier.
• Black hair follicular dysplasia—alopecia of 
black-haired areas only.
• Dermatomyositis—alopecia of face, tip of 
ears, tail, and digits; associated with scale 
crusting and scarring.
Breed-Related Alopecia
• Alopecic breeds—Chinese crested, Mexican 
hairless, Inca hairless, Peruvian Inca orchid, 
American hairless terrier (often associated 
with comedones, folliculitis, and furunculosis).
• Congenital hypotrichosis—cocker spaniel, 
Belgian shepherd, poodle, whippet, beagle, 
French bulldog, Yorkshire terrier, Labrador 
retriever, bichon frise, Lhasa apso, basset hound.
• Color dilution alopecia—blue or fawn 
Doberman pinscher, silver Labrador, cream 
chow chow, blond Irish setter, blue pit bull 
terrier, other breeds with dilute coat colors.
• Melanoderma with alopecia—Yorkshire 
terrier.
terrier.
water spaniel, Portuguese water spaniel, Boston

68 Blackwell’s Five-Minute Veterinary Consult  
A
terrier, Manchester terrier, whippet, Italian 
greyhound, Chihuahua.
chow, Akita, Samoyed, keeshond, Alaskan 
Malamute, Siberian husky.
Rule out metabolic causes such as hyperadreno-  
• Thyroid panel—do not rely on low T4 
(total thyroxine) alone); diagnose hypo- 
• Adrenocorticotropic hormone (ACTH)-
response test, low-dose dexamethasone-
suppression test (LDDST), and high-dose 
dexamethasone-suppression test (HDDST)—
evaluate for hyperadrenocorticism.
• Sex hormone profiles (questionable 
validity, often not useful for diagnosis or 
therapy).
IMAGING
Ultrasonography—evaluate adrenal glands for 
evidence of hyperadrenocorticism.
• Cytology.
• Skin scraping.
• Fungal culture.
• Skin biopsy—very useful to evaluate status 
of follicle/hair growth as well as epidermal 
changes associated with specific conditions.
  TREATMENT
• T reatments depend on the underlying 
causes of alopecia; see specific chapters for 
• Bathing can be useful as adjunctive therapy 
for many conditions.
• Demodicosis or other external parasites —
isoxazoline antiparasitics as per label.• Dermatophytosis—terbinafine, ketoconazole, 
fluconazole, itraconazole, lime sulfur dips, 
griseofulvin.
• Staphylococcal folliculitis—investigate and 
treat underlying cause, shampoo and antibiotic 
therapy.
• Sebaceous adenitis—topical therapy, 
essential fatty acid supplementation, 
cyclosporine.
• Iatrogenic Cushing’s—stop all glucocorti- 
coids.
• Natural hyperadrenocorticism—trilostane, 
mitotane, surgical removal of tumor.
• Hypothyroidism—levothyroxine supple- 
mentation.
• Follicular dysplasia—control concurrent 
allergies and infections.
• Alopecia X and seasonal flank alopecia—
sometimes responds to melatonin.
• Ischemic lesions—consider pentoxifylline.
N/A
None
None
  FOLLOW-UP
Determined by cause.
N/A
N/A
N/A
Dermatophytosis can cause skin lesions in 
humans.
Avoid retinoids and griseofulvin in pregnant 
animals.SEE ALSO
• Flea Bite Hypersensitivity and Flea 
Control.
• Hyperadrenocorticism (Cushing’s 
Syndrome)—Dogs.
• Sertoli Cell T umor.
• HDDST = high-dose dexamethasone-
• LDDST = low-dose dexamethasone-
• T4 = Total thyroxine.
Behrend EN, Kooistra HS, Nelson R, et al. 
Diagnosis of spontaneous canine 
hyperadrenocorticism: 2012 ACVIM 
consensus statement (small animal). J Vet 
Intern Med, 2013 27(6):1292–1304.
Moriello KA, Coyner K, Paterson S, Mignon 
B. Diagnosis and treatment of dermatophytosis 
in dogs and cats: clinical consensus 
guidelines of the World Association for 
Veterinary Dermatology. Vet Dermatol, 
2017, 28(3):266–e68.
Morris DO. Ischemic dermatopathies. Vet 
Clin North Am Small Anim Pract, 2013, 
43(1):99–111.
Vandenabeele S, Declercq J, De Cock H, 
Daminet S. Canine recurrent flank alopecia: 
a synthesis of theory and practice. Vlaams 
Diergeneeskd Tijdschr, 2014, 
83(6):275–283.
Resnick
available onlineAlopecia—Dogs  (continued)

Canine and Feline, Seventh Edition  69
A Alopecia, Noninflammatory—Dogs
  BASICS
• Uncommon alopecic disorders that are 
associated with abnormal hair follicle cycling. 
• Both endocrine and nonendocrine diseases 
can be associated with alopecia. • Definitive 
diagnosis often requires ruling out the more 
common endocrine alopecias.
• Many factors affect the hair cycle, both 
hormonal and nonhormonal. • Increased 
sex hormones can affect the hair cycle. 
Estrogen is a known inhibitor of anagen, 
the growth phase of the hair follicle. • The 
mechanism by which alopecia X influences 
the hair cycle is not known. • Exposure to 
human exogenous hormone replacement 
therapy.
• Behavioral. • Endocrine/metabolic. • Hemic/  
lymphatic/immune. • Skin/exocrine.
GENETICS
Breed predispositions exist for alopecia X; 
however, the mode of inheritance is unknown.
• Hyperestrogenism and hyperandrogenism 
are uncommon to rare causes of alopecia. 
• Alopecia X is relatively common in 
predisposed breeds.
None
Species
Dogs
• Hyperestrogenism and hyperandrogenism—  
no breed predilections.  • Alopecia X—
miniature poodle and plush-coated breeds 
such as Pomeranian, chow chow, Akita, 
Samoyed, keeshond, Alaskan Malamute, and 
Siberian husky; recently described in 
Schipperke breed.
middle-aged to old intact dogs. • Alopecia 
X—1–5 years of age; however, older dogs 
may develop the condition.
• Hyperandrogenism, primarily intact males.  
• Hyperestrogenism, primarily intact females 
or males. • Alopecia X, neutered or intact 
dogs of either sex.
SIGNS
• Overall change in hair coat—dry or 
bleached because hairs not being replaced; lack of normal shed. • Males with hyper- 
estrogenism may attract other male dogs.
• Alopecia—usually diffuse and bilaterally 
symmetric truncal alopecia sparing the head 
and distal extremities; uncommon with 
hyperandrogenism. • Hair coat—may be dry 
or bleached. • Secondary seborrhea, pruritus, 
pyoderma, comedones, ceruminous otitis 
externa, and hyperpigmentation—variable. 
• Enlargement of nipples, mammary glands, 
vulva, prepuce—may be associated with 
hyperestrogenism. • Macular melanosis and 
linear preputial dermatitis—may be associ- 
ated with hyperestrogenism. • Abnormal-
sized or different-sized testicles—may be 
associated with hyperestrogenism or 
hyperandrogenism. • Testicles may also 
appear normal in size. • Tail gland 
hyperplasia and perianal gland hyperplasia—
usually associated with hyperandrogenism. 
• Systemic signs (polyuria/polydipsia [PU/
PD]/polyphagia) are usually not present.
CAUSES
Hyperestrogenism—Females
Estrogen excess associated with cystic ovaries, 
ovarian tumors (rare), exogenous estrogen 
supplementation, or exposure to human 
topical hormone replacement.
Hyperestrogenism—Males
• Estrogen excess due to Sertoli cell tumor 
(most common), seminoma, or interstitial cell 
tumor (rare), or exposure to human topical 
hormone replacement. • Associated with 
male pseudohermaphrodism in miniature 
schnauzers.
Hyperandrogenism—Males
Androgen-producing testicular tumors 
(especially interstitial cell tumors).
Alopecia X
Hairs fail to cycle, but underlying endocrine 
cause has not been identified.
• Intact male and female dogs at increased 
risk for developing testicular tumors and 
ovarian cysts/tumors, respectively.  
• Cryptorchid males at increased risk for 
developing testicular tumors. • Exogenous 
estrogen supplementation. • Exposure to 
therapy. • No known risk factors for alopecia 
X other than breed predisposition.
  DIAGNOSIS
• Inflammatory causes of alopecia 
(pyoderma, demodicosis, and dermato -
phytosis)—usually cause patchy rather than diffuse pattern of alopecia. • Sebaceous 
adenitis—inflammatory cause of alopecia 
more common in specific breeds (Samoyed, 
Akita). • Hypothyroidism and 
hyperadrenocorticism—may cause very 
similar pattern of diffuse alopecia associated 
with lack of hair follicle cycling. • Follicular 
dysplasia including color dilution alopecia 
and black hair follicular dysplasia—alopecia 
should be color restricted. • Patterned 
alopecia of various breeds (dachshund, 
Boston terrier, greyhound, water spaniel, and 
others)—breed-specific alopecia of unknown 
cause. • Seasonal/cyclic/canine flank alopecia—  
alopecia of flank and dorsum, often serpiginous 
patterns with hyperpigmentation, more often 
in short-coated breeds (boxer, English 
bulldog, Airedale) and may recur seasonally. 
• Postclipping alopecia—hair fails to regrow 
following clipping; however, hair regrowth 
occurs within one year. • Telogen 
defluxion—alopecia occurs 1–2 months 
following illness or severe stressful episode 
and usually more sudden in onset, with 
relative ease of epilation.
• Usually unremarkable. • Anemia, 
hypercholesterolemia associated with severe 
hypothyroidism. • Anemia and/or bone 
marrow hypoplasia or aplasia can be 
associated with hyperestrogenism.
• Serum sex hormone concentrations—often 
normal, treat according to suspected 
diagnosis based on clinical signs and ruling 
out other disorders. • Serum estradiol 
concentrations—sometimes elevated in male 
dogs with testicular tumors or female dogs 
with cystic ovaries; however, normal fluctuation 
of estradiol occurs throughout the day, making 
interpretation of estradiol concentrations 
difficult. • Adrenal sex hormone panel not 
useful for diagnosis of alopecia X.
IMAGING
Radiography, ultrasonography, and 
laparoscopy—identify cystic ovaries, ovarian 
tumors, testicular tumors (scrotal or 
abdominal), adrenal tumors, sublumbar 
lymphadenopathy, and possible thoracic 
metastases of malignant tumors.
• Preputial cytology—may demonstrate 
cornification of cells in males with hyper -
estrogenism (similar to bitch in estrus). 
Histologic changes associated with endocrine 
dermatoses (telogen hairs, follicular keratoses, 
hyperkeratosis, excess trichilemmal keratini- 
zation [flame follicles], thin epidermis, and 
thin dermis) may also be seen with 
noninflammatory alopecias including

70 Blackwell’s Five-Minute Veterinary Consult  
A
hyperestrogenism and alopecia X. Histopathology 
will help rule out inflammatory causes of 
alopecia (pyoderma, demodicosis, 
dermatophytosis, sebaceous adenitis) and some 
of the other differentials listed above.
  TREATMENT
DIET
None
Alopecia X is a cosmetic condition resulting in 
coat loss only and there is no definitive cure for 
the hair loss. The risk of treatment should be 
emphasized. Hair regrowth will only occur in a 
portion of dogs regardless of treatment chosen, 
and hair loss may recur months to years later in 
spite of continued treatment.
Hyperestrogenism/Hyperandrogenism
• Castration—scrotal testicular tumors. 
• Exploratory laparotomy—diagnosis and 
surgical removal (ovariohysterectomy and 
castration) for ovarian cysts and tumors and 
abdominal testicular tumors.
Alopecia X
• Neuter intact animals—a certain number 
will regrow hair following neutering; hair 
regrowth may take up to 3 months to become 
evident. • Microneedling technique may 
induce hair regrowth.
General Treatments
• Topical antiseborrheic shampoos—for 
comedones and seborrhea associated with 
alopecia. • Antibiotics and topical antimicrobial 
shampoos—for secondary skin infections 
associated with alopecia.
Alopecia X
• Melatonin—implants (8 mg or 18 mg every 
4–6 months) or oral (3 mg q12h for small 
breeds and 6–12 mg q12h for large breeds); 
evidence of hair regrowth may take up to 3 
months. Effective in approximately 40% of 
cases. Because this treatment is benign, it is 
considered the treatment of choice following 
neutering. Once hair regrowth has occurred, 
discontinue treatment. • Medroxyprogesterone 
acetate—5–10 mg/kg SC q4 weeks for 4 treatments. Hair regrowth can take up to 
6 months. Effective in approximately 
40–50% of cases.
None
• Melatonin at high doses can cause insulin 
resistance. Use caution in treating dogs with 
diabetes mellitus. • Medroxyprogesterone 
acetate can cause mammary nodules and 
cystic endometrial hyperplasia with long-term 
use. Diabetes mellitus has been reported in a 
few dogs.
None
• Mitotane—15–25 mg/kg once daily as 
induction for 5–7 days, followed by twice 
weekly maintenance; hair regrowth occurs 
in portion of dogs treated and can take up 
to 3 months to become evident. Use of this 
drug can result in an Addisonian crisis and 
other side effects, as for treatment of 
Cushing’s syndrome. • T rilostane—dosages 
as described for treatment of Cushing’s 
syndrome; hair regrowth occurs in a portion 
of dogs treated and can take up to 3 months 
to become evident. Use of this drug can 
result in an Addisonian crisis and other side 
effects, as for treatment of Cushing’s 
syndrome.
  FOLLOW-UP
• Medroxyprogesterone acetate—complete 
physical examination and chemistry panel 
regularly. • Mitotane—electrolytes and 
cortisol with adrenocorticotropic hormone 
(ACTH) stimulation testing regularly. 
• T rilostane—electrolytes and cortisol with 
ACTH stimulation testing regularly.
None
None
• Estrogen- and androgen-secreting 
tumors—resolution of signs should occur 
within 3–6 months after castration or 
ovariohysterectomy. • Alopecia X—hair 
regrowth will occur in only a portion of 
dogs regardless of treatment chosen and 
hair loss may recur in spite of continued treatment. Therefore, if hair regrowth 
occurs, discontinue treatment to preserve 
treatment for future recurrence of 
alopecia. Risk of treatment should be 
weighed with the fact that this is a 
cosmetic disease.
• Pyoderma, seborrhea, comedones may be 
associated with alopecia. • Behavioral changes 
associated with hyperestrogenism or hyper- 
androgenism.
None
None
N/A—neutering usually recommended for 
managing these conditions.
SYNONYMS
Alopecia X—growth hormone-responsive 
alopecia, castration-responsive alopecia, 
adrenal hyperplasia-like syndrome, adrenal 
sex hormone imbalance of plush-coated 
breeds, among others.
• PU/PD = polyuria/polydipsia.
https://vetmed.tennessee.edu/vmc/
SmallAnimalHospital/Dermatology
Frank LA. Endocrine and metabolic diseases. 
In: Miller WH, Griffin CE, Campbell KL, 
eds., Muller and Kirk’s Small Animal 
Dermatology, 7th ed. Philadelphia, PA: 
W.B. Saunders, 2013, pp. 501–553.
Frank LA. Alopecia X in a Pomeranian. 
Clinicians Brief, 2017, Nov:26–30.
Stroll S, Dietlin C, Nett-Mettler CS. 
Microneedling as a successful treatment for 
alopecia X in two Pomeranian siblings. Vet 
Dermatol 2015, 26:387–390.
Author  Linda A. Frank
Resnick
available onlineAlopecia, Noninflammatory—Dogs  (continued)

Canine and Feline, Seventh Edition  71
A
 Ameloblastoma
  BASICS
OVERVIEW
• Common oral tumor of odontogenic (tooth 
structure) ectoderm origin.
• Biologically these tumors are benign 
histologically, but possess locally invasive 
properties.
• T umors may arise anywhere within the 
dental arcade.
• Several histologic subtypes exist with 
similar invasive behavior.
• Middle-aged and old dogs.
• Rare in cats.
SIGNS
• Dogs may present with a smooth, firm, 
gingival mass that is usually nonulcerated.
• May be incidental finding during dental 
prophylaxis/procedures. If involving rostral 
dental arcade, incisor teeth can be displaced 
and enveloped by proliferative tissue.
N/A
  DIAGNOSIS
• Epulis.
• Gingival hyperplasia.
• Amelanotic melanoma.
• Plasma cell tumor.
• Other tumors related to the odontogenic 
apparatus.
Unaffected
N/A
IMAGING
• Dental radiographs may show bone 
lysis deep to the superficial mass. Not 
particularly useful for diagnostic or treatment 
planning.
• Regional and distant metastasis has not 
been described.
• CT is ideal for planning surgery or 
radiation therapy, especially in large or caudal 
tumors.
• Deep tissue biopsies are necessary and 
recommended for definitive diagnosis.• Squamous cell carcinoma may be 
misdiagnosed as ameloblastoma.
  TREATMENT
• Surgical excision such as hemi- or total 
mandibulectomy or maxillectomy with 
>1–2 cm margins is recommended as a 
curative treatment option. Always submit 
resected tissue for histopathology, in order to 
confirm the original diagnosis, and evaluate 
soft tissue and bone margins.
• Radiation therapy may provide long-term 
control in large tumors, or when owners 
decline surgery.
• Intralesional chemotherapy with bleomycin 
has been reported, but results are generally 
inferior to those of surgery or radiation.
N/A
N/A
  FOLLOW-UP
Careful oral examination at 1, 3, 6, 9, and 
12 months after definitive treatment is 
recommended to monitor for local 
Amory JT, Reetz JA, Sanchez MD, et al. 
Computed tomographic characteristics of 
odontogenic neoplasms in dogs. Vet Radiol 
Ultrasound 2014, 55(2):147–158.
Fiani N, Verstraete FJ, Kass PH, Cox DP . 
Clinicopathologic characterization of 
odontogenic tumors and focal fibrous 
hyperplasia in dogs: 152 cases (1995–2005). 
J Am Vet Med Assoc 2011, 
238(4):495–500.
Goldschmidt SL, Bell CM, Hetzel S, Soukup 
J. Clinical characterization of canine 
acanthomatous ameloblastoma (CAA) in 
263 dogs and the influence of postsurgical histopathological margin on local 
recurrence. J Vet Dent 2017, 
34(4):241–247.

72 Blackwell’s Five-Minute Veterinary Consult  
AAmphetamine and ADD/ADHD Medication Toxicosis
  BASICS
Acute neurologic, neuromuscular, and cardiac 
toxicosis as the result of excessive consumption 
of amphetamine or a derivative. May be due 
to ingestion of prescription medications or 
illegal drugs.
• Amphetamine and its derivatives belong to the 
CNS stimulant class phenylethylamines. Various 
substitutions of the basic phenylethylamine 
structure account for many pharmaceutical 
and illicit compounds found today.
• Amphetamine is a sympathomimetic that is 
structurally related to norepinephrine.
• Central action—stimulates cortical centers 
including cerebral cortex, medullary respiratory 
center, and reticular activating systems.
• Peripheral action—directly stimulates alpha 
and beta receptors and stimulates release of 
norepinephrine from stores in adrenergic 
nerve terminals.
• Amphetamine may slow catecholamine 
metabolism by inhibition of monoamine 
oxidase.
• Several different product formulations, 
including immediate and extended release 
and topical patch.
• Amphetamines are well absorbed orally; 
peak plasma levels are generally reached in 
1–3 hours; this may be delayed with extended 
release formulations.
• Metabolism is minimal.
• The half-life, which varies from 7 to 34 
hours, and rate of excretion of unchanged 
amphetamine in the urine are both dependent 
upon urine pH, with shorter half-lives 
associated with more acidic urine.
• Clinical signs may be seen at doses below 
1 mg/kg.
• Oral lethal dose in dogs for most 
amphetamines ranges from 10 mg/kg to 
23 mg/kg and for methamphetamine sulfate 
it is 9–11 mg/kg. Oral lethal dose for 
amphetamine sulfate is 20–27 mg/kg.
• Amphetamine and its derivatives are used 
in humans to treat attention deficit disorder 
(ADD)/attention deficit hyperactivity 
disorder (ADHD), narcolepsy, and obesity.
• Illicit use of amphetamines in humans is 
also prevalent.
• Cardiovascular—stimulation most 
common: tachycardia and hypertension.
• Nervous—stimulation most common, 
depression uncommon.
• Neuromuscular—stimulation: muscle 
tremors and seizures.
• Respiratory—stimulation, tachypnea.
• Ophthalmic—mydriasis.• Gastrointestinal (GI)—anorexia, vomiting, 
diarrhea.
N/A
Species
Dogs and cats, although more prevalent in dogs.
N/A
N/A
N/A
SIGNS
• Abnormal behavior—usually hyperactivity, 
anxiety or pacing, anorexia, fast heart rate, 
panting; observed or evidence of exposure by 
owner/caretaker.
• Onset of signs typically begins within 30 
minutes to 6 hours post ingestion; depends 
on product formulation.
• Nervous—hyperactivity, agitation, 
restlessness, head bobbing, pacing, circling, 
vocalization, disorientation, hyperesthesia, 
ataxia, lethargy or depression (less common).
• Cardiovascular—tachycardia or bradycardia 
(less common, may be reflexive), hypertension.
• Neuromuscular—muscle fasciculation or 
tremors, seizures.
• Gastrointestinal—vomiting, diarrhea, 
anorexia, excessive salivation.
• Respiratory—tachypnea.
• Ophthalmic—mydriasis with possibly poor 
to unresponsive pupillary light response.
• Other—hyperthermia.
CAUSES
Accidental ingestion or administration, 
malicious poisoning.
Households with children or adults currently 
taking prescription or illicit amphetamine or 
derivative.
  DIAGNOSIS
• Strychnine.
• Organochlorine insecticides.
• Methylxanthine.
• 4-aminopyridine.
• Metaldehyde.
• Phenylpropanolamine.
• Albuterol.
• Nicotine.
• T remorgenic mycotoxins.
• Hypernatremia.
• Pseudoephedrine, phenylephrine.• 5-fluorouracil.
• Ma huang, guarana, or ephedra.
• CBC—generally normal with mild to 
moderate intoxications; disseminated 
intravascular coagulopathy secondary to 
severe hyperthermia (rare).
• Chemistry—generally normal with mild to 
moderate intoxications.
• Azotemia—prerenal: secondary to 
dehydration; renal: secondary to 
rhabdomyolysis and myoglobinuria (rare).
• Elevated liver enzymes—secondary to 
seizures and/or hyperthermia (rare).
• Hypoglycemia.
• Urinalysis—evidence of myoglobinuria, 
urine specific gravity (high: prerenal azotemia; 
isosthenuria: renal failure).
• Electrolytes—imbalances secondary to GI 
effects.
• Acid-base status—acidosis may occur.
• Over-the-counter urine drug screens—
watch for false positive or negative; consult 
user handbook for further information.
• Amphetamines are present in blood, urine, 
and saliva; consult with local veterinary 
diagnostic lab or human hospital for 
availability and proper sample submission.
IMAGING
N/A
• ECG for presence of any tachyarrhythmia 
or less commonly bradyarrhythmia.
• Blood pressure—identification of 
On necropsy presence of amphetamines may 
be found in gastric contents, urine, plasma, 
liver, kidney, or muscle.
  TREATMENT
Majority of cases require emergency inpatient 
intensive care management.
• Intravenous fluid therapy to correct 
dehydration and electrolyte imbalances as 
well as support renal function and promote 
excretion of amphetamines; use blood 
pressure to help guide fluid rate.
• Cool intravenous fluids, fans, cool water 
baths for hyperthermia.
ACTIVITY
Minimize activity and stimuli.
DIET
Withhold food if moderately to severely 
affected. Bland diet for few days post 
exposure if significant GI signs were noted.

Canine and Feline, Seventh Edition  73
A
In case of exposure, owner should contact 
local veterinarian or veterinary poison center 
immediately.
N/A
Decontamination
• Induce emesis—if recent exposure and pet 
is not already symptomatic.
• Apomorphine—0.04 mg/kg IV, subcon- 
junctival.
• Hydrogen peroxide 3%—2.2 mL/kg, 
maximum dose 45 mL.
• Gastric lavage if extremely large ingestion 
or patient is already symptomatic.
• Activated charcoal with cathartic.
CNS Signs of Stimulation
• Acepromazine 0.05–1.0 mg/kg IV/IM, start 
low and titrate to effect.
• Chlorpromazine 0.5 mg/kg IV, titrate up as 
needed.
• Cyproheptadine (serotonin antagonist)—
dogs, 1.1 mg/kg orally or rectally, may be 
repeated q8h as needed for signs consistent 
with serotonin syndrome; cats, 2–4 mg/cat, 
may repeat q12h as needed for signs 
consistent with serotonin syndrome.
• Methocarbamol (for muscle tremors)— 
50–220 mg/kg IV, titrate to effect; do not 
exceed 330 mg/kg/day.
Cardiovascular Signs
• Tachyarrhythmia—beta blockers such as 
propranolol 0.02–0.04 mg/kg IV or esmolol 
or metoprolol; caution using propranolol in 
significantly hypertensive patient.
• Ventricular premature contractions—
lidocaine: dogs at 2–4 mg/kg IV (to maxi-  
mum of 8 mg/kg over 10-minute period); 
cats: start with 0.1–0.4 mg/kg and increase 
cautiously to 0.25–0.75 mg/kg IV slowly if no 
response; cats are reportedly very sensitive to 
lidocaine, so monitor carefully if used.
Promote Elimination
Ascorbic acid or ammonium chloride—for 
urinary acidification to promote elimination; 
however, only use if can measure acid-base status.
• While diazepam has been successfully used 
to treat amphetamine exposures, there is 
evidence that benzodiazepines may intensify 
neurologic signs.
• Urinary acidification if unable to monitor 
acid-base status or if myoglobinuria is present.
• Inducing emesis in symptomatic patient.PRECAUTIONS
N/A
• Amphetamines inhibit metabolism of 
adrenergic blockers (doxazosin, phenoxy -
benzamine, prazosin, terazosin), 
phenobarbital, and phenytoin.
• Amphetamines potentiate metabolism of 
coumarin anticoagulants, monoamine oxidase 
inhibitors, opioid analgesics, and tricyclic 
antidepressants.
Phenobarbital, pentobarbital, and propofol 
for CNS stimulatory signs.
  FOLLOW-UP
• Monitor in hospital until resolution of 
• If severely affected, monitor liver and 
kidney values every 24 hours for 72 hours or 
until resolution.
All medications and illicit drugs should be 
kept out of pets’ reach at all times.
Acute renal failure secondary to myoglobinuria 
or disseminated intravascular coagulation 
(DIC; rare).
EXPECTED COURSE 
AND PROGNOSIS
• Expected course of clinical signs is 12–72 
hours, depending on dose, product formulation, 
effectiveness of decontamination and 
treatment, and rate of elimination.
• Prognosis—most patients do well with prompt 
and appropriate veterinary care. Seizures or severe 
hyperthermia may be poor prognostic indicator.
N/A
N/A
Pets exposed to human waste products from 
those taking amphetamines or derivatives 
could become symptomatic.
Amphetamines are a known teratogen in 
humans. They have been found to cross the 
placenta in animals and may also be found 
in milk.SYNONYMS
• Common brand names of prescription 
amphetamine drugs and their active 
ingredient—Adderall® (amphetamine and 
dextroamphetamine); Ritalin®, Metadate®, 
and Concerta® (methylphenidate); Daytrana® 
(methylphenidate transdermal patch); 
Focalin® (dexmethylphenidate); Vyvanse® 
(lisdexamfetamine); Cylert® (pemoline); 
Adipex-P® (phentermine); Dexedrine® 
(dextroamphetamine).
• Illicit drug street names—ice, glass, 
crank, speed, uppers, ecstasy, meth, and 
many others.
SEE ALSO
• Antidepressant Toxicosis—SSRIs and 
SNRIs.
• Antidepressant Toxicosis—T ricyclics.
• Pseudoephedrine/Phenylephrine Toxicosis.
• ADD = attention deficit disorder.
• ADHD = attention deficit hyperactivity 
disorder.
• https://www.aspcapro.org/animal-health/
toxicology-poison-control
• http://www.petpoisonhelpline.com
Stern LA, Schell M. Management of attention-
deficit disorder and attention-deficit/
hyperactivity disorder drug intoxication in 
dogs and cats. Vet Clin North Am Small 
Anim Pract 2012, 42(2):279–287.
Teitler JB. Evaluation of a human on-site 
urine multi drug test for emergency use 
with dogs. J Am Anim Hosp Assoc 2009, 
45(2):59–66.
Volmer PA. Human drugs of abuse. In: 
Bonagua JD, T wedt DC, eds., Current 
Veterinary Therapy XIV. St. Louis, MO: 
Elsevier, 2009, pp. 144–145.
Volmer PA. “Recreational” drugs. In: Peterson 
ME, Talcott PA, eds., Small Animal Toxicology, 
309–334.
Wismer T. Amphetamines. In: Osweiler GD, 
Hovda LR, Brutlag AG, Lee JL, eds. 
Blackwell’s Five-Minute Veterinary Consult 
Clinical Companion Small Animal 
Toxicology. Ames, IA: Wiley-Blackwell, 
2011, pp. 125–130.
Author  Kirsten E. Waratuke
Consulting Editor  Lynn R. Hovda(continued)  Amphetamine and ADD/ADHD Medication Toxicosis

74 Blackwell’s Five-Minute Veterinary Consult  
A
  BASICS
Group of conditions of diverse causes in 
which extracellular deposition of insoluble 
fibrillar proteins (amyloid) in various organs 
and tissues compromises normal function.
• Patients usually affected by reactive (secondary) 
amyloidosis; tissue deposits contain amyloid A 
protein (AA), fragment of acute‐phase reactant 
protein called serum amyloid A protein (SAA). 
• Macrophage‐derived cytokines, e.g., IL‐1 and 
IL‐6, stimulate hepatocytes to synthesize SAA. 
• Cellular and extracellular components 
involved in formation and deposition of AA. 
• Specific pathophysiology varies among 
different species and breeds; reactive 
amyloidosis occurs as familial disease in 
Chinese Shar-Pei dog and Abyssinian cat. 
• Chinese Shar-Pei dog—mutation involving 
overexpression of HAS2  results in 
overproduction of hyaluronic acid, which acts 
as danger signal activating inflammasome 
pathway and IL‐1 production; this mutation 
linked to increased likelihood of developing 
shar‐pei autoinflammatory disease (SPAID), 
and also responsible for breed’s meat‐mouth 
phenotype; amyloid deposition occurs in 
medulla of all dogs, with majority of dogs also 
having glomerular involvement. • Non‐shar‐
pei dogs—amyloid deposits found more 
commonly in glomeruli than medulla. 
• Abyssinian cat—amyloid deposits usually 
found in medulla, but may occur in glomeruli. 
• Siamese and oriental shorthair cats with 
familial amyloidosis—amyloid deposition 
occurs in liver. • Pancreatic islet amyloid 
polypeptide, or amylin, deposits in pancreas of 
old cats; amylin secreted with insulin by 
pancreatic beta cells; chronic increased stimulus 
for secretion of amylin by beta cells (e.g., states 
of insulin resistance) leads to pancreatic islet 
cell amyloidosis.
• Renal/urologic—predilection for renal AA 
deposition. • Liver, spleen, adrenal glands, 
pancreas, tracheobronchial tree, gastrointestinal 
tract also may be affected.
GENETICS
• Familial amyloidosis occurs in Chinese 
Shar-Pei, English foxhound, and beagle dogs, 
and in Abyssinian, oriental shorthair, and 
Siamese cats. • A genetic mutation that 
increases likelihood of SPAID in shar‐pei dogs 
has been identified; chronic inflammatory 
episodes in SPAID result in renal amyloid 
deposition.
Uncommon, occurs mostly in dogs; rare in 
cats, except Abyssinian, Siamese, and oriental 
shorthair.SIGNALMENT
Species
• Dog—Chinese Shar-Pei, beagle, English 
foxhound, Walker hound, collies. • Cat—
Abyssinian, Siamese, oriental shorthair.
• Cats—mean age at diagnosis 7 years; range 
1–17 years; Abyssinian cats with familial renal 
amyloidosis usually die by 5 years of age; 
Siamese cats with familial amyloidosis of liver 
and thyroid gland usually develop signs of 
liver disease when 1–4 years old. • Dogs—
mean age at diagnosis 9 years; range 1–15 
years; Chinese Shar-Pei affected younger, with 
median age at diagnosis of 5 years, range 
3.6–17 years. • Prevalence increases with age.
None
SIGNS
Clinical signs depend on organs affected; 
usually caused by kidney involvement.
• No clear history of predisposing disorder in 
most cases. • Anorexia, lethargy, polyuria/
polydipsia, weight loss, vomiting. • Owners 
may appreciate ascites and peripheral edema 
in animals with glomerular amyloidosis. 
• Chinese Shar-Pei dogs may have history of 
previous episodic joint swelling and high 
fever that resolves spontaneously within few 
days (SPAID). • Siamese and oriental 
shorthair cats may present with acute collapse 
and hemoabdomen due to spontaneous 
hepatic fracture.
• Related to primary inflammatory or 
neoplastic disease process. • Animals with renal 
disease may have muscle wasting, abnormal 
renal palpation, uremic ulceration, hypertensive 
fundic lesions. • Fluid retention may be present 
(ascites, peripheral edema). • Chinese Shar-Pei 
dogs may have evidence of SPAID if present 
during active flare‐up (joint effusion and pain, 
fever). • Signs of thromboembolic disease may 
be present in up to 40% of dogs with renal 
amyloidosis (dyspnea with pulmonary embolism, 
caudal paresis with aortic embolism). • Siamese 
and oriental shorthair cats with hepatic 
dysfunction may have jaundice; pallor and 
abdominal fluid wave may be present with 
hepatic fracture and hemoabdomen.
CAUSES
• Neoplasia and chronic infectious and 
noninfectious inflammatory conditions can 
be found in 30–50% of dogs with reactive 
amyloidosis. • Chronic inflammation—
systemic mycoses, chronic bacterial infections, 
parasitic infections (dirofilariasis, leishmaniasis, 
hepatozoonosis), inflammatory and immune‐mediated diseases (SPAID, systemic 
lupus erythematosus, juvenile polyarteritis of 
beagle); amyloid deposits can be found in up 
to 35% of feline immunodeficiency virus 
(FIV)‐positive cats. • Neoplasia (lymphoma, 
plasmacytoma, multiple myeloma, mammary 
tumors, testicular tumors). • Familial—
Chinese Shar-Pei, English foxhound, and 
beagle dogs; Abyssinian, Siamese, and 
oriental shorthair cats. • Other—cyclic 
hematopoiesis in gray collies.
  DIAGNOSIS
• Depends on organ affected. • Renal 
(glomerular) amyloidosis—immune‐complex 
glomerulonephritis (GN; e.g., membrano- 
proliferative GN [MPGN], membranous GN 
[MGN]), non‐immune‐complex GN, 
glomerulosclerosis, focal segmental 
glomerulosclerosis, other glomerulopathies. 
• Renal (medullary) amyloidosis—other 
causes of medullary renal disease (e.g., 
pyelonephritis, chronic interstitial nephritis). 
• Hepatic amyloidosis—other causes of 
hepatic dysfunction (e.g., infectious, 
inflammatory, portosystemic shunt, 
neoplasia); in animals with hepatic fracture 
and hemoabdomen, consider other causes of 
hemoabdomen (e.g., hemangiosarcoma, 
hematoma).
• CBC—nonregenerative anemia found in 
some dogs and cats. • Chemistry profile—
changes reflect distribution of amyloid 
deposition; with renal medullary amyloidosis, 
azotemia, hyperphosphatemia, metabolic 
acidosis may be seen; hypoalbuminemia 
common with glomerular amyloidosis; 
hyperglobulinemia may be seen due to 
underlying inflammatory condition resulting 
in reactive amyloidosis. • Urinalysis—
isosthenuria, proteinuria, cylindruria 
common with renal amyloidosis; proteinuria 
may be mild or absent in patients without 
glomerular amyloidosis; isosthenuria may not 
be present in patients without medullary 
involvement.
• Urine protein–creatinine ratio (UPC) should 
be performed for quantification of proteinuria. 
• Urine sodium dodecyl sulfate–polyacrylamide 
gel electrophoresis (SDS‐PAGE)—can 
differentiate between high and low molecular 
weight proteinuria; high molecular weight 
proteinuria expected with glomerular disease.
IMAGING
Abdominal Radiographic Findings
Kidneys—usually small in affected cats; small, 
normal size, or large in affected dogs.Amyloidosis

Canine and Feline, Seventh Edition  75
A
Abdominal Ultrasonographic Findings
• Renal size, shape, and architecture variable; 
kidneys usually hyperechoic and small in 
affected cats; may be small, normal size, or large 
in affected dogs. • Echogenic effusion may be 
present in cats with hepatic amyloidosis, due to 
Renal biopsy—histopathology required for 
definitive diagnosis, and to rule out other 
causes of GN; ultrasound‐guided sampling 
preferred over surgical methods; samples 
should be assessed under dissecting microscope 
to ensure glomeruli present; risk factors for 
hemorrhage include body weight <5 kg, 
serum creatinine >5 mg/dL.
• Amyloid deposits appear homogeneous and 
eosinophilic when stained by hematoxylin and 
eosin and viewed by conventional light micro  - 
scopy. • Demonstrate green birefringence after 
Congo red staining when viewed under 
polarized light; AA amyloid loses Congo red 
affinity after permanganate oxidation. 
• Ultrastructurally, fibrils are 9–11 nm in 
diameter, nonbranching, haphazardly arranged.
  TREATMENT
• Identify underlying inflammatory and 
neoplastic processes and treat if possible. 
• Animals symptomatic from uremia or 
clinically dehydrated may require hospitalization. 
• Stable, euhydrated animals can be managed 
as outpatients with standard therapy for 
proteinuria.
DIET
• Low‐protein, low‐phosphorous renal diets 
recommended for animals with proteinuria 
and/or renal dysfunction. • Esophageal 
feeding tube placement should be considered 
for enteral hydration and nutritional support.
• Discuss progression of disease and potential 
for underlying primary disease process. 
• Discuss familial predisposition in suscep- 
tible breeds.
Management of Proteinuria
• Animals with proteinuria should be 
treated with standard therapy for proteinuria 
(see Glomerulonephritis and Proteinuria). 
• Patients with evidence of active thrombo- 
embolic disease require antiplatelet drugs 
(clopidogrel or aspirin) and/or anticoagulant therapy (heparin, low molecular weight 
heparin, or factor Xa inhibitors).
Management of Renal Insufficiency 
and Hypertension
• As indicated by IRIS guidelines for stage of 
renal disease. • Amlodipine (0.3–0.8 mg/kg 
PO SID) as first‐line therapy for management 
of hypertension.
Management of Amyloid Deposition
• Dimethylsulfoxide (DMSO; dogs—90% 
DMSO diluted 1 : 4 with sterile water 
subcutaneously at dosage of 90 mg/kg 3 times 
per week) may help patients by solubilizing 
amyloid fibrils, reducing serum concentration 
of SAA, and reducing interstitial inflammation 
and fibrosis in affected kidneys, though benefit 
of DMSO is controversial. • Colchicine 
(dogs—0.01–0.04 mg/kg PO q24h) impairs 
release of SAA from hepatocytes, and used for 
amyloidosis in humans with familial 
Mediterranean fever (familial amyloidosis 
similar in pathology to SPAID); no evidence 
for benefit once patient develops renal 
amyloidosis and dysfunction; colchicine used 
particularly in shar‐pei dogs with episodic 
fever or polyarthritis before development of 
renal failure.
• Dose reduction of drugs may be needed in 
patients with renal insufficiency. • Use of 
nonsteroidal anti‐inflammatory drugs 
(NSAIDs) should be avoided in patients with 
renal insufficiency; SPAID flare‐ups usually 
resolve on their own, do not require NSAIDs. 
• Animals with glomerular disease are prone 
to overhydration due to abnormal renal 
sodium handling; fluid therapy should be 
used judiciously, only to correct dehydration; 
even patients with mild hypoalbuminemia 
can become significantly overhydrated from 
inappropriate fluid therapy.
  FOLLOW‐UP
BUN, creatinine, albumin, electrolyte 
concentrations, 3-day pooled UPC, and 
blood pressure 1 month following medication 
changes, and every 3-4 months in stable 
patients.
Do not breed affected animals.
• Renal insufficiency and progressive chronic 
kidney disease. • Nephrotic syndrome and 
fluid overload. • Thromboembolic disease 
occurs in up to 40% of dogs, but uncommon 
in cats. • Hepatic rupture causing hemoabdo- 
men (hepatic amyloidosis). • Otic and airway 
hemorrhage (vascular amyloidosis) reported.EXPECTED COURSE AND PROGNOSIS
• Disease is progressive and usually advanced at 
time of diagnosis. In one study, median survival 
time for all dogs with renal amyloidosis 5 days 
(range: 0–443 days), shorter in Chinese 
Shar-Pei dogs (2 days, range: 0–368 days). 
• Serum creatinine concentration has signifi-  
cant negative association with survival. • Cats 
with renal insufficiency because of amyloidosis 
usually survive <1 year; cats with systemic 
amyloidosis (i.e., liver, vascular) have grave 
prognosis due to complications such as hepatic 
fracture and pulmonary hemorrhage.
• Shar‐pei autoinflammatory disease. 
• Juvenile polyarteritis in beagles.
SEE ALSO
• Chronic Kidney Disease.
• Glomerulonephritis.
• Proteinuria.
• AA = amyloid A protein. • BUN = blood urea 
nitrogen. • DMSO = dimethylsulfoxide.  
• FIV = feline immunodeficiency virus.  
• GN = glomerulonephritis.  
• MGN = membranous GN.  
• MPGN = membranoproliferative GN. 
• NSAID = nonsteroidal anti‐inflammatory 
drug. • SAA = serum amyloid A protein. 
• SDS‐PAGE = sodium dodecyl sulfate–
polyacrylamide gel electrophoresis.  
• SPAID = shar‐pei autoinflammatory disease. 
• UPC = urine protein–creatinine ratio.
Bartges J, Wall J. Amyloidosis. In Bartges J, 
Polzin DJ. Nephrology and Urology of 
Small Animals. Oxford: Wiley‐Blackwell, 
2011, pp. 547–554.
Olsson M, Meadows JRS, T ruvé K, et al. A 
novel unstable duplication upstream of 
HAS2 predisposes to a breed‐defining skin 
phenotype and a periodic fever syndrome in 
Chinese Shar‐Pei dogs. PLoS Genet 2011, 
7:e1001332.
Segev G, Cowgill LD, Jessen S et al. Renal 
amyloidosis in dogs: a retrospective study of 
91 cases with comparison of the disease 
between Shar‐Pei and non‐Shar‐Pei dogs. 
J Vet Intern Med 2012, 26:259–268.
Author  Nahvid M. Etedali
editors acknowledge the prior contributions 
of Helio S. Autran de Morais and Stephen 
P . DiBartola.
  Client Education Handout  
available online(continued)  Amyloidosis

76 Blackwell’s Five-Minute Veterinary Consult  
AAnaerobic Infections
  BASICS
OVERVIEW
• Anaerobic bacteria require low oxygen 
tension to live, and constitute a large portion 
of the normal flora.
• May be Gram-positive or Gram-negative 
cocci or rods, and individual organisms vary 
in potential to withstand oxygen exposure.
• Most common genera— Bacteroides , 
Fusobacterium , Actinomyces , Propionibacterium , 
Peptostreptococcus  (enteric Streptococcus ), 
Porphyromonas , and Clostridium .
• Most anaerobic infections are polymicrobial 
and can contain anaerobes admixed with 
facultative anaerobes or aerobic bacteria 
(especially E. coli ).
• Injurious toxins and enzymes elaborated by 
the organisms may allow extension of 
infection into adjacent, healthy tissue.
SIGNS
• Depend on body system involved.
• Areas associated with mucous membranes 
are more commonly associated with anaerobic 
• It is possible to overlook anaerobes in an 
infectious process, leading to confusion in 
interpreting culture results and selection of 
antimicrobials.
• Foul odor associated with wound or 
exudative discharge.
• Gas in the tissue or exudates.
• Discolored tissue.
• Ascites (peritonitis), pleural effusion 
(pyothorax), or signs of pyometra (vaginal 
discharge, palpable structure in caudal 
abdomen).
• Dental disease.
• Wounds or deep abscesses that do not heal 
as anticipated.
• Usually caused by normal flora; break in 
protective barriers allows bacterial invasion.
• Predisposing factors—immunosuppression, 
bite wounds, dental disease, open fractures, 
abdominal surgery, migrating foreign bodies.
  DIAGNOSIS
• Infection with aerobic or fungal organ-
isms—culture recommended.• Necrosis due to trauma or hypoperfusion.
• Neutrophilic leukocytosis, monocytosis.
• Biochemical abnormalities depend on 
specific organ involvement.
• Sepsis suggested by leukocytosis/leukopenia, 
hypoglycemia, hypoalbuminemia.
• Anaerobic bacterial culture often unrewarding 
because of fastidious growth requirements 
and errors in sample handling.
 ◦Appropriate media and containers should 
be available prior to sample collection.
 ◦Samples should not be refrigerated.
 ◦Suitable samples for culture include fluid 
or tissue.
IMAGING
As indicated for individual patient; gas may 
be apparent radiographically.
• Cytologic inspection of fluid or tissue 
reveals degenerate neutrophils with morpho-
logically diverse intracellular and extracellular 
bacteria; presence of large filamentous 
bacteria is suggestive.
• Gram staining should be performed on 
sample.
  TREATMENT
• Wound drainage/debridement should be 
established as soon as possible—including 
placement of drains or thoracostomy tubes, as 
 ◦Combine with systemic antimicrobial 
therapy.
 ◦Devitalized tissue should be aggressively 
debrided.
 ◦Improves local blood flow and increases 
tissue oxygen tension.
• Exploratory surgery indicated when anaerobic 
organisms complicate osteomyelitis or intraab -
dominal disease (e.g., pyometra, peritonitis).
• Antimicrobial therapy alone is unlikely to 
be successful without debridement or 
drainage.
 ◦Antibiotic selection—largely empiric 
(difficult to isolate anaerobes).
 ◦Because most anaerobic infections are 
polymicrobial, therapy targeted against 
both anaerobes and aerobic organisms is 
indicated.• Amoxicillin with clavulanate (22–30 mg/kg 
PO q12h)—antibiotic of choice; clavulanate 
improves activity against Bacteroides . 
Injectable potentiated beta-lactams include 
ampicillin/sulbactam, ticarcillin/clavulanate, 
and piperacillin/tazobactam.
• Cefoxitin (30 mg/kg IV/IM q6–8h)— 
reliable activity against anaerobes.
• Clindamycin (11–33 mg/kg PO q12–24h; 
10 mg/kg IV q12h)—useful for respiratory 
tract infections.
• Chloramphenicol (25–50 mg/kg PO q8h, 
dogs only)—good tissue penetration but 
bacteriostatic; concern for human exposure.
• Metronidazole (10 mg/kg IV/PO q12h)—
useful against all clinically significant 
anaerobes except Actinomyces .
• Cefovecin (8 mg/kg SC)—infections 
originating from the periodontal cavity, skin, 
or urinary tract.
• Imipenem—significant activity against 
serious, resistant infections, not first-line 
choice.
• Quinolones—newer third-generation 
quinolones (e.g., pradofloxacin) have 
some activity against anaerobes; others 
ineffective.
N/A
  FOLLOW-UP
Varies with the circumstances of each 
patient.
Localized infection may progress to systemic 
infection if not appropriately identified and 
treated.
Dependent upon identification and 
resolution of the underlying cause; long-term 
antibiotic therapy may be required.
Greene CE, Jang SS. Anaerobic infections. In: 
Saunders Elsevier, 2011, pp. 411–416.

Canine and Feline, Seventh Edition  77
A Anal Sac Disorders
  BASICS
OVERVIEW
• Anal sacs are reservoirs for secretions 
normally evacuated by compression during 
defecation. •  Normal gland secretions vary 
widely in consistency and color. •  Disorders 
include impaction, infection/sacculitis, and 
neoplasia. •  T reatment options include 
manual expression, flushing, antibiotics, and 
surgical excision.
Impaction/Infection
• Dogs and cats (rarely)—no age or sex 
predisposition. •  Breeds predisposed 
(impaction)—smaller breeds (miniature/toy 
poodle, Chihuahua, American cocker and 
English springer spaniel).
Neoplasia
• Adenocarcinoma—English cocker spaniel 
most commonly reported.
SIGNS
• Anal/perianal pruritus—often manifested 
by “scooting.” •  Hesitancy to defecate. 
• Tenesmus. •  Tail chasing. •  Foul-smelling, 
nonfeces anal discharge. •  Refusal to sit and/
or lift tail. •  Cats—excessive licking of the 
ventral abdomen and tail head. •  Abscess—
often unilateral; localized pain and discharge.
Neoplasia
• Mass or swelling in perianal region. 
• Tenesmus, constipation, polyuria/polydipsia 
(due to hypercalcemia with adenocarcinoma). 
• L4-Cd myelopathy reported in one cat 
(adenocarcinoma).
• Predisposing factors—changes in muscle 
tone, fecal form (soft stool/diarrhea), secretion 
character/volume leading to decreased/lack of 
expression; intestinal disease, obesity, endocrine 
disease. •  Infection/abscess—chronic or 
recurrent impactions.
  DIAGNOSIS
Impaction/Infection/Neoplasia
• Hypersensitivity (flea, atopy, food). 
• Tapeworm infestation. •  Tail fold bacterial 
folliculitis. •  Malassezia dermatitis. • Compulsive disorder (anal licking). •  Colitis 
or other intestinal disorder. •  Keratinization 
disorder. •  Anal sac neoplasia (adenocarcinoma, 
squamous cell carcinoma, melanoma). •  Perianal 
adenoma, adenocarcinoma. •  Perianal fistulae.
Neoplasia
Hypercalcemia—anal sac adenocarcinoma.
None unless indicated by an underlying cause.
IMAGING
• Digital palpation of anal sacs—should not be 
palpable externally. •  Expression of anal sac 
contents—varies widely in gross appearance and 
microscopic characteristics. •  Cytology (normal 
dogs/cats)—one study reports Gram-positive 
cocci/rods, Gram-negative cocci/rods, yeast, 
nondegenerate neutrophils without phagocytosis, 
mononuclear cells, and corneocytes; erythrocytes 
uncommonly found in dogs, rare in cats. Another 
study had similar findings but with intracellular 
bacteria in clinically normal dog anal sacs.
• Cytology—no statistically significant 
difference in bacterial counts or inflammatory 
cells found between normal dogs and those with 
clinical signs of anal sac disease. •  Bacterial 
culture and susceptibility— Bacillus , Escherichia 
coli, Micrococcus , Proteus mirabilis , Streptococcus  
spp., others possible.
Neoplasia
• Surgical excision with histopathology.
  TREATMENT
• Gentle manual expression and/or flushing of 
contents. Sedation may be necessary to flush 
severely impacted or painful anal sacs. 
• Feeding high-fiber diets may help natural 
expression of anal sacs. •  Identification of 
underlying causes of predisposing disease. 
• Chronic disease—anal sac excision. 
• Infection—infusion of antibiotic and/or 
corticosteroid medications directly into the anal 
sacs, drainage of abscesses, use of appropriate 
oral antibiotics and/or antiyeast medication.
Neoplasia
• Surgical excision and staging; combine with 
chemotherapy.  MEDICATIONS
Infection
Use of appropriate oral antibiotics: cephalexin 
(dog, 22–30 mg/kg q12h), amoxicillin 
trihydrate–clavulanate potassium (dog, 
13.75 mg/kg q12h; cat, 62.5 mg/cat q12h), 
clindamycin (dog, 11–22 mg/kg q24h; cat, 
11–30 mg/kg q24h), trimethoprim–sul-
famethoxasole (dog, 15 mg/kg q12h); 
metronidazole (dog, 15–25 mg/kg q12–24h); 
enrofloxacin (dog, 10–20 mg/kg q24h), 
orbifloxacin (dog/cat, 5 mg/kg q24h).
T rimethoprim–sulfamethoxasole—
Dobermans highly susceptible to type III 
hypersensitivity reactions.
  FOLLOW-UP
• Reassess patients weekly initially, then as 
necessary to monitor healing. •  Manually 
express anal sac contents and/or flush contents 
until sacs empty without intervention. 
• T rimethoprim–sulfamethoxasole—monitor 
tear production, liver function; affects thyroid 
serum values.
SEE ALSO
• Adenocarcinoma, Anal Sac
• Perianal Fistula
Helton Rhodes KA, Werner A. Blackwell’s 
Five-Minute Veterinary Consult: Clinical 
Companion: Small Animal Dermatology, 3rd 
ed. Hoboken, NJ: Wiley-Blackwell, 2018.
James DJ, Griffin CE, Polissar NL, Neradilek 
MB. Comparison of anal sac cytological 
findings and behaviour in clinically normal 
dogs and those affected with anal sac 
disease. Vet Derm 2010, 22:80–87.
Resnick

78 Blackwell’s Five-Minute Veterinary Consult  
AAnaphylaxis
  BASICS
• Acute manifestation of a type I hyper­
sensitivity reaction mediated through the 
introduction of an antigen into a host having 
antigen ­specific antibodies of the 
immunoglobulin (Ig) E subclass.
• Binding of antigen to mast cells sensitized 
with IgE results in the release of preformed 
and newly synthesized chemical mediators.
• Anaphylactic reactions may be localized 
(atopy) or systemic (anaphylactic shock).
• Anaphylaxis not mediated by IgE is 
designated an anaphylactoid (nonimmunologic) 
reaction and will not be discussed; however, 
the treatment is the same for either reaction.
• First exposure of the patient to a particular 
antigen (allergen) causes a humoral response 
and results in production of IgE, which binds 
to the surface of mast cells. The patient is then 
considered to be sensitized to that antigen.
• Second exposure to the antigen results in 
cross­linking of two or more IgE molecules 
on the cell surface, resulting in mast cell 
degranulation and activation. Release of mast 
cell granules initiates an anaphylactic reaction.
• Major mast cell–derived mediators include 
histamine, eosinophilic chemotactic factor, 
arachidonic acid and metabolites (e.g., 
prostaglandins, leukotrienes, and thromboxanes), 
platelet ­activating factor, and proteases. 
Release of these mediators causes an 
inflammatory response characterized by 
increased vascular permeability, smooth 
muscle contraction, inflammatory cell influx, 
and tissue damage.
• Clinical manifestations depend on the route 
of antigen exposure, the dose of antigen, and 
the level and specificity of the IgE response.
• Gastrointestinal—salivation, vomiting, and 
diarrhea.
• Cardiovascular—hypotension, cardiac 
arrhythmias, shock.
• Respiratory—dyspnea, cyanosis/hypoxemia.
• Skin/exocrine—pruritus, urticaria, and edema.
• Hepatobiliary (dogs)—portal hypertension, 
vasoconstriction, ascites.
GENETICS
Familial basis reported for type I hypersensi­
tivity reaction in dogs.
• Localized type I hypersensitivity reactions 
not uncommon.
• Systemic type I hypersensitivity reactions rare.
NoneSIGNALMENT
Species
• Dogs—numerous breeds documented as 
having a predilection for developing atopy.
• Cats—no breeds documented as having 
predilection for atopy.
• Dogs—age of clinical onset ranges from 
3 months to several years; most affected 
animals 1–3 years old.
• Cats—age of clinical onset ranges from 
6 months to 2 years.
• Dogs—atopy more common in females, 
no predilection for acute anaphylaxis.
• Cats—no reported sex predilection.
SIGNS
• Initial clinical signs vary depending on the 
route of exposure to the inciting antigen 
(allergen).
• Shock—a severe anaphylactic reaction 
attributable to cardiovascular collapse and 
impaired oxygen delivery.
• May be localized to the site of exposure, but 
may progress to a systemic reaction.
• Onset of signs usually within minutes, 
history of exposure to insects or medications.
• Dogs—pruritus, urticaria, vomiting, 
defecation, urination, collapse if severe.
• Cats—intense pruritus about the head, 
dyspnea, salivation, vomiting, collapse if 
severe.
• Localized cutaneous edema and erythemia 
at the site of exposure, macropapular rash.
• Dyspnea, cyanosis, respiratory wheezes.
• Tachycardia, hypotension (poor pulses), 
pale or muddy mucous membranes in 
animals with shock.
• Conjunctivitis, lacrimation.
• Painful abdomen, hepatomegaly (dogs).
• Hyperexcitability possible in early stages, 
altered mentation from hypoperfusion in 
systemic anaphylaxis.
CAUSES
Virtually any agent; those commonly 
reported include venoms (bees, wasps and 
hornets, fire ants, etc.), blood ­based products 
(including antivenom and other animal ­
derived products), vaccines, medications, 
and foods.
Previous exposure (sensitization) increases 
the chance of the animal developing a 
reaction.  DIAGNOSIS
• Other types of shock.
• Asthma.
• Depends on the major organ system 
involved or if reaction is localized; diagnosis 
can be made largely based on history and 
Because of the acute onset of disease, no tests 
reliably predict individual susceptibility.
• In heartworm ­endemic areas, a positive 
heartworm test may indicate a worm embolus 
as a cause for anaphylaxis.
• If ascites is present, abdominocentesis may 
reveal hemoperitoneum.
• Intradermal skin testing to identify allergens.
• Radioallergosorbent test to quantify the 
concentration of serum IgE specific for a 
particular antigen.
IMAGING
• Radiographic findings—if hemoperitoneum 
is present, ascites may be apparent in abdominal 
• Ultrasonographic findings—may show 
presence of edema in the gall bladder wall 
(“halo sign”) or peritoneal effusion.
Limited, because a severely allergic animal can 
develop an anaphylactic reaction when 
exposed to even small quantities of antigen.
• Lesions vary, depending on severity of 
reaction, from localized cutaneous edema to 
severe pulmonary edema (in cats) and visceral 
pooling of blood (in dogs).
• Other nonspecific findings vary and are 
characteristic of shock.
• Nonspecific characteristics of localized 
reactions include edema, vasculitis, and 
thromboembolism.
  TREATMENT
In an acutely affected animal, the reaction is 
considered a medical emergency requiring 
hospitalization and intensive care.
Elimination of inciting antigen, if possible.
Systemic Anaphylaxis
• Goal—emergency life support through the 
maintenance of an open airway, treating 
circulatory collapse, and reestablishing 
physiologic parameters.

Canine and Feline, Seventh Edition  79
A
• Administer fluids (isotonic crystalloids and/
or colloids) intravenously to counteract 
hypotension; in severely affected animals, 
pressor agents (e.g., pinephrine) may be 
necessary to support blood pressure.
• In coagulopathic animals, transfusion with 
fresh frozen plasma or red blood cell–
containing products may be indicated.
Localized Anaphylaxis
Goal—limit the reaction and prevent 
progression to a systemic reaction.
ACTIVITY
N/A
DIET
If a food ­based allergen is suspected 
(uncommon), avoid foods associated with 
hypersensitivity reaction.
• Discuss the unpredictable nature of the 
disease.
• Discuss the need to recognize that the 
animal has an allergic condition that may 
require immediate medical care.
None
• Epinephrine hydrochloride (5–10  μg/kg 
[0.005–0.01 mg/kg] IV/IM).
• Corticosteroids—dexamethasone sodium 
phosphate (0.1–0.5 mg/kg IV), methylpredni ­ 
solone sodium succinate (30 mg/kg IV).
• Isotonic crystalloid fluids (20–30 mL/kg IV 
over 15–20 minutes, followed by reassessment 
and additional boluses if necessary, targeting a 
maximum of 90 mL/kg in dogs and 60 mL/kg 
in cats) to treat hypotension and relative 
hypovolemia.
• Atropine (0.02–0.04 mg/kg IV) to treat 
symptomatic bradycardia.• Bronchodilators—aminophylline (10 mg/
kg IM or slowly IV) in severely dyspneic 
patients; albuterol inhalers (90  μg/actuation, 
via inhalation).
• Oxygen should be administered to 
hypoxemic patients, either by mask or a 
cage with an elevated oxygen content 
(targeting a 40% fraction of inspired 
oxygen [FiO2]).
• Norepinephrine (0.5–3  μg/kg/min IV).
• Antihistamines—diphenhydramine 
hydrochloride (0.5–1.0 mg/kg IV/IM/PO); 
famotidine (0.5–1.0 mg/kg IV); ranitidine 
(0.5–2.5 mg/kg IV).
• Prednisolone (1–2 mg/kg PO).
• If shock develops, initiate treatment for a 
None
Localized reaction can develop into systemic 
reaction.
N/A
N/A
  FOLLOW-UP
• Closely monitor hospitalized patients for 
24–48 hours.
• In patients with systemic anaphylaxis, 
monitoring should focus on normalization 
and monitoring of blood pressure, heart rate 
and rhythm, urine output, coagulation status, 
and oxygenation.
• If patients have continued fluid loss (e.g., 
due to diarrhea or vomiting), fluid admini ­ 
stration rates should be adjusted accordingly.PREVENTION/AVOIDANCE
If inciting antigen (allergen) can be identified, 
eliminate or reduce exposure.
None
• If localized reaction is treated early, prognosis 
is good.
• Some patients with systemic anaphylaxis 
that respond initially can have a recurrence of 
shock, usually within 12 hours of initial 
presentation.
• If the animal is in shock on presentation, 
prognosis is guarded.
None
None
None
N/A
SEE ALSO
Shock, hypovolemic.
• FiO2 = fraction of inspired oxygen.
Shmuel DL, Cortes Y. Anaphylaxis in dogs 
and cats. J Vet Emerg Crit Care 2013, 
23(4):377–394.
Author  Paul W. Snyder
Consulting Editor  Melinda S. Camus
available online(continued)  Anaphylaxis

80 Blackwell’s Five-Minute Veterinary Consult  
AAnemia of Chronic Kidney Disease
  BASICS
OVERVIEW
• Progressive decrease in packed cell volume 
(PCV), red blood cell (RBC) count, and 
hemoglobin, and hypoplasia of erythroid 
elements of bone marrow are predictable 
features of chronic kidney disease (CKD).
• Anemia is normocytic, normochromic, 
nonregenerative, and proportional to stage of 
CKD; underlying cause of anemia is 
multifactorial.
• Gastrointestinal (GI) blood loss, reduced 
RBC survival, deficiencies in iron and/or 
folate, cytokines, and inflammatory mediators 
may be involved; however, primary cause of 
anemia in CKD is inadequate production of 
erythropoietin (EPO) by the kidneys.
• EPO is hormone that regulates bone 
marrow RBC generation and is produced in 
peritubular interstitial cells in response to 
decreased tissue oxygen.
Any patient with advanced CKD—juvenile 
or acquired.
SIGNS
• Anemia contributes to anorexia, weight 
loss, fatigue, lethargy, depression, weakness, 
and behavior changes characterizing CKD.
• Pallor.
• Tachypnea.
• Tachycardia.
• Systolic murmur.
• All inherited, congenital, and acquired 
forms of CKD.
• Exacerbated by iron deficiency, inflammatory 
or neoplastic disease, GI bleeding, hemolysis, 
and myeloproliferative disorders.
  DIAGNOSIS
• Anemia of chronic infectious, inflammatory, 
or neoplastic disease; myeloproliferative 
disease; chronic blood loss; aplastic anemia; 
endocrine disease; drug reaction; chronic 
immune-mediated, toxic, viral, rickettsial, or 
parasitic anemia; hemodilution.
• Regenerative anemia excludes diagnosis of 
anemia of CKD.
• Normocytic, normochromic, hypoprolif- 
erative anemia.
• Reticulocytes—low corrected indices and 
absolute counts (≤10,000/ μL).
• Typically, IRIS stage 3 or greater CKD.• High blood urea nitrogen 
(BUN) : creatinine ratio may predict 
concurrent GI bleeding.
• Serum iron—normal or variably low.
• T ransferrin saturation—normal or variably 
low ( <20%).
• Feline leukemia virus (FeLV), feline 
immunodeficiency virus (FIV), mycoplasma, 
or rickettsial testing to exclude infection-
induced myelodyscrasia.
• Serum EPO—inappropriately normal or 
low.
IMAGING
• Small, irregular kidneys with loss or 
disruption of renal architecture often seen.
• Less commonly enlarged, polycystic, 
hydronephrotic, infiltrative.
Bone marrow cytology—erythroid hypo-
plasia; myeloid : erythroid ratio normal or 
high; stainable iron normal or low.
  TREATMENT
• Stabilize azotemia in patients with uremic 
crisis.
• Ensure adequate nutrition.
• Stabilize any metabolic derangement (e.g., 
acidosis) that could contribute to shortened 
RBC lifespan.
• Minimize micronutrient deficiencies that 
could reduce RBC production.
• Identify and manage GI bleeding.
• Parenteral iron supplementation if needed.
• Correct systemic hypertension.
Blood Transfusion
• Short-term, rapid correction needed if 
hypoxic distress (typically PCV ≤15%)—give 
compatible packed RBCs.
• May transfuse intermittently for prolonged 
management, although compatibility issues 
are likely to occur.
• Preferred treatment is EPO support for 
progressive or symptomatic anemia.
EPO Replacement
• Darbepoetin alfa (Aranesp®)—an analogue 
of recombinant human EPO (r-HuEPO) 
with prolonged half-life and sustained effects; 
very effective with less tendency for antibody 
induction; should be used preferentially to 
epoetin alfa.
• Target PCV—dogs, 30–35%; cats, 30%.• Dosage—0.8–1.0  μg/kg SC once weekly 
until PCV reaches low end of target, then 
decrease to q2-4 weeks as needed to maintain 
target; check PCV first to avoid overtreatment.
• If PCV exceeds target, discontinue until 
upper target range is achieved, then increase 
dosing interval.
• Iron dextran (5–10 mg/kg IM) should be 
administered as needed to normalize serum 
iron and transferrin saturation before initiating 
and during EPO treatment; injectable iron 
more effective than oral preparations.
• r-HuEPO—original synthetic erythropoiesis-
stimulating protein, replica of human EPO 
(Epogen® and Procrit®); higher potential for 
anti-r-HuEPO antibody production and pure 
red cell aplasia (PRCA); use no longer 
recommended,
Anabolic Steroids
Not indicated.
  FOLLOW-UP
• PCV and blood pressure.
• Iron and transferrin saturation—at 1, 3, 
and 6 months, then semiannually.
• Discontinue EPO if patient develops 
evidence of polycythemia, local or systemic 
sensitivity, PRCA, or refractory hypertension.
EPO Related
• Development of polycythemia, seizures, 
hypertension, iron depletion, injection pain, 
and mucocutaneous reactions.
• Development of PRCA during epoetin alfa 
treatment suggests formation of anti-r-
HuEPO antibodies, which neutralize r-HuEPO 
and native EPO, causing severe anemia in 
20–30% of animals; often reversible with 
cessation of treatment.
• Development of anti-r-HuEPO antibodies 
occurs in <10% of patients receiving 
darbepoetin alfa.
• Signs associated with production of 
anti-r-HuEPO antibodies include decreasing 
PCV, erythroid hypoplasia, reticulocyte count 
nearing zero, and myeloid : erythroid ratio ≥8.
• EPO replacements should be used cautiously 
or withheld if hypertension or iron deficiency 
develops; treatment can be reinstituted once 
hypertension or iron deficiency is corrected.
Transfusion Related
• Incompatibility reaction.
• Circulatory or iron overload.
• Systemic hypertension.
• T ransmissible infection.
• Correction of anemia increases appetite, 
activity, and quality of life.

Canine and Feline, Seventh Edition  81
A
• Use of EPO replacement agents requires 
careful assessment of risks and benefits.
• Short-term prognosis depends on severity 
of CKD.
• Long-term prognosis is guarded to poor 
because of underlying CKD.
• EPO = erythropoietin.
• FeLV = feline leukemia virus.• FIV = feline immunodeficiency virus.
• PRCA = pure red cell aplasia.
• r-HuEPO = recombinant human 
erythropoietin.
Chalhoub S, Langston C, Eatroff A. Anemia of 
renal disease: what it is, what to do, and what’s 
new. J Feline Med Surg 2011, 13:629–640.
Chalhoub S, Langston C, Farrely J. The use 
of Darbepoetin to stimulate erythropoiesis 
in anemia of chronic kidney disease. J Vet 
Intern Med 2012; 26:363–369.Cowgill LD, James KM, Lew JK, et al. Use of 
recombinant human erythropoietin for 
management of anemia in dogs and cats 
with renal failure. J Am Vet Med Assoc 
1998, 212:521–528.
Fiocchi EH, Cowgill LD, Brown DC, et al. 
The use of Darbepoetin to stimulate 
erythropoiesis in the treatment of anemia of 
chronic kidney disease in dogs. J Vet Intern 
Med 2017, 31:476–485.
Acknowledgment  The authors and book 
editors acknowledge the prior contribution of 
Ilaria Lippi.(continued)  Anemia of Chronic Kidney Disease

82 Blackwell’s Five-Minute Veterinary Consult  
AAnemia, Aplastic
  BASICS
OVERVIEW
• A disorder of hematopoietic precursor cells 
characterized by replacement of normal bone 
marrow with adipose tissue. There is decreased 
production of granulocytes, erythrocytes, and 
platelets, resulting in pancytopenia in the 
peripheral blood. The disease is sometimes 
also referred to as aplastic pancytopenia. •  In 
the acute form, neutropenia and thrombo­
cytopenia predominate because of the shorter 
life spans of these cells; in the chronic form, 
nonregenerative anemia also occurs. In both 
forms, the bone marrow exhibits variable 
degrees of panhypoplasia. •  Precipitating 
causes can include infectious diseases, drug or 
toxin exposure, and starvation; immune ­
mediated mechanisms are often suspected. 
• Hemic/lymphatic/immune systems 
affected.
Dogs and cats, no apparent breed or sex 
predilection. In one study, the mean age of 
nine affected dogs was 3 years.
SIGNS
• Acute form—fever, petechial 
hemorrhages, epistaxis, hematuria, melena; 
i.e., signs due to neutropenia and thrombo ­ 
cytopenia. •  Chronic form—pale mucous 
membranes, weakness, lethargy; i.e., signs 
due to anemia, in addition to signs observed 
in acute forms.
Often not identified.
Infectious Agents
immunodeficiency virus (FIV). •  Canine and 
feline parvovirus. •  Rickettsial organisms 
(e.g., Ehrlichia  spp.)
Drugs and Chemicals
• Estrogen (exogenous administration, Sertoli 
and interstitial cell tumors). •  Methimazole 
(cats). •  Chemotherapeutic drugs, including 
azathioprine, cyclophosphamide, cytosine 
arabinoside, doxorubicin, vinblastine, and 
hydroxyurea. •  Antibiotics, including 
trimethoprim–sulfadiazine, cephalosporins, 
and chloramphenicol. •  Griseofulvin. 
• Nonsteroidal anti ­inflammatory drugs 
(NSAIDs), including phenylbutazone and 
meclofenamic acid. •  Fenbendazole, 
albendazole. •  Captopril. •  Quinidine. 
• Thiacetarsamide. •  Ionizing radiation. 
• Mycotoxins (cats).  DIAGNOSIS
Causes of pancytopenia with normal to 
increased bone marrow cellularity (e.g., 
myelodysplastic syndromes, leukemias, 
myelofibrosis).
• Leukopenia characterized by neutropenia 
with or without lymphopenia. •  Normocytic, 
normochromic, nonregenerative anemia. 
• Thrombocytopenia.
• Immunologic tests for infectious 
diseases, e.g., serologic titers, ELISA, 
immunofluorescent antibody (IFA). 
• PCR for infectious agents. •  Positive 
tests for antierythrocyte antibodies 
(Coombs’ test) and/or antinuclear antibody 
(ANA) may indicate immune ­mediated 
mechanisms.
IMAGING
N/A
• Bone marrow aspiration—frequently an 
inadequate or fatty sample is obtained 
because of decreased hematopoietic tissue 
and replacement by adipocytes. •  Bone 
marrow core biopsy—permits an evaluation 
of architecture and reveals hypoplasia  
of cell lines and replacement by adipose 
tissue.
  TREATMENT
Supportive treatment, antibiotics, blood 
component therapy, as dictated by clinical 
condition and results of infectious disease 
testing.
• Cyclosporine A—10–25 mg/kg PO q12h 
(dogs), 4–5 mg/kg PO q12h (cats). 
• Mycophenolate mofetil—10 mg/kg PO/IV 
q12h. •  Recombinant hematopoietic growth 
factors, e.g., recombinant human granulocyte 
colony ­stimulating factor (rhG ­CSF) 5  μg/
kg/day SC. •  Androgen and corticosteroid 
administration have been largely unsuccessful.Other Drugs
• Antibiotics to treat secondary infections if 
fever and neutropenia present. •  Whole or 
component blood transfusion if indicated.
N/A
  FOLLOW-UP
• Daily physical examination. •  CBC every 
3–5 days. •  Repeat bone marrow evaluation 
if necessary.
• Castration of cryptorchid males (to prevent 
development of Sertoli or interstitial cell 
tumors). •  Vaccination for infectious diseases. 
• Frequent monitoring of CBC in cancer 
patients receiving chemotherapy or radiation.
• Sepsis. •  Hemorrhage.
• Guarded to poor. •  Recovery of hemato ­ 
poiesis may take weeks to months, if it occurs 
at all. •  Spontaneous recovery occasionally 
occurs, especially in younger animals.
SEE ALSO
Pancytopenia.
• ANA = antinuclear antibody.
• IFA = immunofluorescent antibody (test).
drug.
• rhG­CSF = recombinant human granulocyte 
colony ­stimulating factor.
Brazzell JL, Weiss DJ. A retrospective study of 
aplastic pancytopenia in the dog: 9 cases 
(1996–2003). Vet Clin Path 2006, 
35:413–417.
Weiss DJ. Aplastic anemia. In: Weiss DJ, 
Wardrop KJ, eds., Schalm’s Veterinary 
Hematology, 6th ed. Ames, IA: Blackwell, 
2010, pp. 256–260.
Author  R. Darren Wood

Canine and Feline, Seventh Edition  83
A Anemia, Heinz Body
  BASICS
OVERVIEW
• Heinz bodies occur in red blood cells (RBCs) 
following damage from chemical or dietary 
oxidants, can cause hemolytic anemia. •  When 
oxidants overwhelm protective reductive 
pathways in RBCs, denaturation of hemoglobin 
(Hb) causes precipitation and attachment to 
cell membrane. •  RBCs with Heinz bodies are 
removed by splenic macrophages, and 
occasionally undergo intravascular lysis, 
forming ghost cells. •  The spleen may 
occasionally remove Heinz bodies, resulting in 
spherocytes. •  Cats more susceptible to Heinz 
body formation because have less reductive 
enzymatic capacity and closed splenic 
circulation, preventing macrophages from 
removing Heinz bodies. •  Healthy cats may 
have low numbers of Heinz bodies without 
anemia. •  Heinz bodies reported in patients 
with hyperthyroidism, lymphoma, and diabetes 
mellitus. •  Heinz bodies may be accompanied 
by methemoglobinemia (Hb containing Fe3+) 
and/or eccentrocytes (indicating oxidative 
damage to RBC membranes).
No species, sex, breed, or age disposition.
SIGNS
• Oxidant exposure. •  Sudden onset of 
weakness, lethargy, or anorexia secondary to 
anemia. •  Signs related to underlying disease 
if present.
• Pale, occasionally icteric mucous membranes, 
dark or chocolate-colored if methemoglobine -
mia. •  Tachypnea, tachycardia.
• Dietary—onions (raw, cooked, dehydrated, 
powdered), garlic, propylene glycol (cats). 
• Drugs—acetaminophen, phenacetin (cats), 
phenazopyridine (cats), methylene blue, 
vitamin K1 or K3 (dogs), DL-methionine 
(cats), benzocaine, phenylhydrazine (dogs), 
propofol (cats). •  Miscellaneous—zinc (bolts, 
pennies minted after 1982, dermatologic or 
sun creams), naphthalene (mothballs), skunk 
musk.
  DIAGNOSIS
Immune-mediated or hemoparasitic hemolysis.CBC/BIOCHEMISTRY/URINALYSIS
• Diagnosis of Heinz body anemia requires 
regenerative anemia, evidence of hemolytic 
process, presence of Heinz bodies in peripheral 
blood, and elimination of other causes of 
hemolysis or blood loss. •  Regenerative 
anemia; severity depends on dose and 
duration of oxidant exposure. •  Hb 
concentration and mean corpuscular 
hemoglobin concentration (MCHC) may be 
falsely increased due to Heinz body 
interference with measurement. •  Heinz 
bodies on routinely stained blood smear 
appear as small, nonstaining to pale red, 
round inclusions that may protrude from 
RBC surface. •  Single, small ( <0.5 μm) 
Heinz bodies may be found in cats without 
anemia, but large or multiple Heinz bodies in 
anemic cat suggest hemolytic anemia. •  Dogs 
may have concurrent eccentrocytosis. 
• Hyperbilirubinemia, bilirubinuria, hemo- 
globinemia, and hemoglobinuria possible 
with intravascular hemolysis.
• New methylene blue stains Heinz bodies 
blue, making them easy to identify and quantify 
on a blood smear. •  Measure methemoglobin 
or perform spot test if blood is dark or chocolate-  
colored. •  Serum zinc concentration.
IMAGING
Abdominal radiographs may reveal metallic 
foreign bodies contributing to zinc toxicity.
N/A
  TREATMENT
• Immediate identification and removal of 
oxidant may be sufficient, though often takes 
several days after exposure for severity of 
anemia to reach nadir. •  T reatment depends 
on severity and may include IV fluids, RBC 
transfusions, oxygen, and restricted activity. 
• Endoscopy or surgery to remove metallic 
items in gastrointestinal tract.
• Acetaminophen toxicity in cats—  
N-acetylcysteine (Mucomyst®) 140 mg/kg PO/
IV, followed by seven additional treatments of 
70 mg/kg PO/IV q8h). •  Ascorbic acid 
(vitamin C) 30 mg/kg PO q6-12h, to reduce 
methemoglobin concentrations.Alternative Drug(s)
Use of dietary antioxidants (e.g., bioflavo-
noids) is controversial, but may help prevent 
further formation of Heinz bodies.
Administration of methylene blue to treat 
methemoglobinemia may exacerbate Heinz 
body formation.
  FOLLOW-UP
Serial CBCs and review of blood smears to 
assess RBC regeneration and disappearance of 
Heinz bodies.
Counsel clients about identifying and 
preventing exposure to oxidant compounds.
Without proper treatment and removal of 
oxidant, condition can be fatal.
Prognosis is good with removal of oxidant 
and supportive care once hemolytic crisis 
is over.
SEE ALSO
• Acetaminophen (APAP) Toxicosis.
• Zinc Toxicosis.
• Hb = hemoglobin.
• MCHC = mean corpuscular hemoglobin 
Andrews D. Disorders of red blood cells. 
In: Handbook of Small Animal Practice, 
5th ed. St. Louis, MO: Saunders, 2008, 
pp. 632–635.
Desnoyers M. Anemias associated with 
oxidative injury. In: Schalm’s Veterinary 
2010, pp. 239–245.
Author  Melinda S. Camus
editors acknowledge the prior contribution 
of Jennifer S. Thomas.

84 Blackwell’s Five-Minute Veterinary Consult  
AAnemia, Immune-Mediated
  BASICS
Accelerated removal or hemolysis of red blood 
cells (RBCs) due to a type II hypersensitivity 
reaction.
• Antibodies form against endogenous RBC 
antigens (primary/nonassociative immune-
mediated hemolytic anemia [IMHA]), or 
RBC membrane antigens, or antigens 
altered by infectious organisms, drugs, or 
neoplasia (secondary/associative IMHA). 
• Immunoglobulin deposited on RBC 
membrane, causing either direct intra -
vascular hemolysis or accelerated 
extravascular removal by monocyte/
macrophage system. •  Intravascular 
hemolysis occurs when adsorbed antibodies 
(especially immunoglobulin [Ig] M) activate 
complement. •  Extravascular removal of 
RBCs occurs when RBCs coated with 
antibodies (especially IgG) are engulfed by 
splenic macrophages. •  RBC agglutination 
occurs when IgM or high titers of IgG 
causes RBC bridging. •  Nonregenerative 
IMHA caused by immune-mediated 
destruction of RBC precursors in bone 
marrow.
• Hemic/lymphatic/immune—destruction of 
RBCs, release of proinflammatory mediators, 
disseminated intravascular coagulation (DIC). 
• Cardiovascular—signs of anemia, thrombo -
embolism. •  Hepatobiliary—hyperbiliru-
binemia, icterus, bilirubinuria; centrilobular 
necrosis. •  Respiratory—tachypnea 
 (secondary to anemia or inflammation), 
hypoxemia (pulmonary thromboembolism 
[PTE]). •  Integument—rare: cold-type IMHA 
causes necrosis of extremities and ear tips.
GENETICS
Cocker spaniels are at increased risk.
Most common hemolytic anemia of dogs, 
relatively rare in cats.
Secondary IMHA may have higher prevalence 
where associated infectious diseases endemic; 
incidence may vary seasonally.
Species
• Cocker spaniel, English springer 
spaniel, Old English sheepdog, Doberman 
pinscher, collie, bichon frise, miniature 
pinscher, Finnish spitz. •  Domestic 
shorthair cats.Mean Age and Range
• Dogs—mean age 5–6 years (range: 1–13 
years). •  Cats—mean age 2 years (range: 
0.5–9 years).
• Female dogs at higher risk. •  Male cats 
overrepresented.
SIGNS
• Lethargy/weakness/collapse. •  Anorexia. 
• Dyspnea, tachypnea. •  Vomiting and/or 
diarrhea. •  Pigmenturia. •  Pica (cats).
• Pale mucous membranes, tachycardia, 
tachypnea. •  Splenomegaly/hepatomegaly. 
• Icterus and pigmenturia (hemoglobin or 
bilirubin). •  Fever/lymphadenopathy. 
• Systolic heart murmur. •  Petechiae, 
ecchymoses, or melena (if concurrent 
thrombocytopenia or DIC). •  Other findings 
possible (e.g., joint pain) when IMHA is 
component of systemic lupus erythematosus 
(SLE). •  Necrosis of extremities and ear tips 
in cold-type IMHA (rare).
Primary IMHA
Poorly characterized immune dysregulation.
Secondary IMHA
• Infectious causes—hemotrophic 
Mycoplasma  spp., Ehrlichia  spp., Anaplasma 
phagocytophilum , Anaplasma platys , Babesia  
spp., Leishmaniasis , Dirofilaria immitis , 
feline leukemia virus (FeLV), feline immuno- 
deficiency virus (FIV), chronic bacterial 
infection. •  Neoplasia—lymphoma, 
lymphoid leukemia, hemangiosarcoma, 
hemophagic histiocytic sarcoma. •  Drugs—
penicillins, cephalosporins, propylthiouracil, 
methimazole, sulfonamides. •  SLE. 
• Neonatal isoerythrolysis. •  Dog erythrocyte 
antigen (DEA) incompatible blood transfusion. 
• Vaccination, surgery, hormonal changes, or 
other stressful events hypothesized as 
potential triggers.
  DIAGNOSIS
Dogs
• Toxicity (zinc, onions, garlic, naphthalene, 
skunk musk). •  Snake/spider envenomation 
(coral snakes, recluse spiders). •  Severe 
hypophosphatemia. •  Anemia due to 
hemorrhage, hemoperitoneum. 
• Microangiopathic anemia due to splenic 
neoplasia or torsion. •  Pyruvate kinase or 
phosphofructokinase deficiency.Cats
• Toxicity (acetaminophen, zinc, onions, 
garlic). •  Severe hypophosphatemia. 
• Congenital feline porphyria. •  Increased 
osmotic fragility (Abyssinian, Somali).
• CBC—anemia, normal to high mean 
cell volume (MCV), spherocytosis, 
polychromasia, ghost cells, leukocytosis with 
neutrophilia and left shift, monocytosis; 
anemia nonregenerative in 30% of dogs and 
50% of cats. •  Serum biochemistry—
hyperbilirubinemia, high alanine 
aminotransferase (ALT). •  Urinalysis—
hemoglobinuria, bilirubinuria.
• Positive saline agglutination test. •  Direct 
antiglobulin (Coombs’) test—positive  
in up to 75% of animals with IMHA. 
• Reticulocytosis if regenerative. 
• Thrombocytopenia—60% of dogs. 
• Prolonged activated partial thromboplastin 
time (APTT), ± prolonged prothrombin time 
(PT), increased fibrin degradation products 
(FDP) and d-dimer, decreased antithrombin 
in animals with DIC. •  Blood smear—
evidence of hematologic parasites. 
• Infectious disease testing—especially 
Babesia  spp. (serology, PCR), Mycoplasma 
hemofelis  (PCR), other vector-borne 
pathogens.
IMAGING
Abdominal radiography, ultrasonography—
hepatomegaly/splenomegaly, neoplasia.
Bone marrow aspirate to identify nonregen-
erative (RBC precursor-directed) IMHA or 
myelofibrosis in chronic cases.
• Hepatosplenomegaly, centrilobular hepatic 
necrosis. •  Splenic and hepatic extramedullary 
hematopoiesis. •  PTE and DIC.
  TREATMENT
• Inpatient intensive care during acute 
hemolytic crisis and if complications 
such as DIC, PTE, thrombocytopenia, 
gastrointestinal (GI) bleeding, or need 
for multiple transfusions occur. 
• Outpatient when PCV stable, hemolysis 
controlled, and clinical signs of anemia 
resolved.
• Fluid therapy as needed. •  Packed RBCs 
(or whole blood), fresh frozen plasma (FFP) if 
coagulopathic. •  Oxygen therapy as needed. 
• Monitor for complications.

Canine and Feline, Seventh Edition  85
A
ACTIVITY
Cage rest.
DIET
N/A
• IMHA can be fatal and difficult to 
treat, with guarded prognosis. •  Lifelong 
maintenance therapy may be needed; 
side effects may be severe. •  Disease may 
recur.
Splenectomy can be considered if medical 
management fails.
• Corticosteroids—prednisone 2–3 mg/kg/
day PO; dexamethasone sodium phosphate 
(0.2–0.4 mg/kg IV q24h) can be used in 
patients unable to take oral medication. 
• Adjunctive immunosuppressants (if poor 
response to corticosteroids or to avoid side 
effects of prednisone)—cyclosporine 5 mg/kg 
PO q12h, cats: 0.5–3 mg/kg PO q12h; 
mycophenolate mofetil 8–12 mg/kg PO/IV 
q12h; azathioprine 2 mg/kg PO q24h, can 
decrease to 0.5–1.0 mg/kg PO q48h after 3 
weeks or if bone marrow suppression occurs, 
monitor for side effects; do not use in cats . 
• Once PCV above 30%, decrease prednisone 
dosage to 1 mg/kg PO q12h; then taper by 
maximum rate of 25–50% per month over 
3–6-month period, depending upon PCV 
and severity of side effects; additional 
immunosuppressant drugs may be tapered as 
well. •  For prevention of thromboembolism 
consider unfractionated heparin 150–300 U/
kg SC q6–8h (dose adjusted based on APTT 
prolongation or measurement of anti-Xa 
activity) and/or clopidogrel 1–2 mg/kg PO 
q24h; low molecular weight heparins 
(enoxaparin 0.8 mg/kg SC q6–8h or dalteparin 
150 U/kg SC q8h) or rivaroxaban (0.5–
1.0 mg/kg PO q24h) may be considered in 
lieu of unfractionated heparin. •  Address 
underlying cause (secondary IMHA). 
• Therapeutic plasma exchange/plasmapheresis 
may be useful adjunctive therapy.
Anticoagulant medications should be used 
cautiously in patients with thrombocytopenia 
(<40,000 platelets/ μL).
• Prednisone/prednisolone can cause signs of 
hyperadrenocorticism and may increase risk of 
PTE, pancreatitis, diabetes mellitus, secondary 
infection, gastric ulcers (consider gastric 
protectants). •  Immunosuppressive drugs can cause bone marrow suppression, secondary 
infection, pancreatitis (azathioprine), GI upset 
(cyclosporine, azathioprine, mycophenolate 
mofetil), gingival hyperplasia, papillomatosis 
(cyclosporine), infertility.
• Chlorambucil—for cats, 0.1–0.2 mg/kg 
PO q24h initially, then q48h. •  Human IV 
immunoglobulin (hIVIG; 0.5–1 g/kg IV) in 
dogs not responding to other therapies.
  FOLLOW-UP
• Monitor heart rate, respiratory rate, body 
temperature frequently. •  Monitor for 
adverse reactions to treatment. •  If PTE 
suspected, CT angiography indicated for 
diagnosis; oxygenation can be assessed with 
pulse oximetry or arterial blood gas analysis. 
• Initially, check packed cell volume (PCV) 
daily until stable, then every 1–2 weeks for 2 
months; if still stable, recheck monthly for 6 
months, then 2–4 times/year. •  CBC and 
reticulocyte count at least monthly; if 
neutrophil count falls <3,000 cells/ μL, 
discontinue cytotoxic drugs until count 
recovers; reinstitute at lower dosage.
Consider need for vaccination on case-by-case 
basis in dogs with IMHA; measurement of titers 
prior to elective vaccinations may be indicated.
• Pulmonary/multiorgan thromboembolism. 
• DIC. •  Centrilobular hepatic necrosis and 
renal tubular necrosis secondary to hypoxia. 
• Infection secondary to immunosuppressive 
therapy. •  GI ulceration due to high-dose 
glucocorticoids. •  Iatrogenic 
• Mortality—30–70% (dog), 24% (cat). 
• Hyperbilirubinemia >5 mg/dL, autoagglu-  
tination, intravascular hemolysis, severe 
thrombocytopenia, hypoalbuminemia 
associated with poorer prognosis. •  Response 
to treatment may take weeks to months; 
nonregenerative IMHA may have more 
gradual onset than typical IMHA and be 
slower to respond to treatment. Most 
patients receive immunosuppressive 
therapy for 4–8 months.
See above.ZOONOTIC POTENTIAL
None
SYNONYMS
• Autoimmune hemolytic anemia. 
• Immune-mediated anemia.
SEE ALSO
• Anemia, Regenerative.
• Cold Agglutinin Disease.
• APTT = activated partial thromboplastin 
time.
• DEA = dog erythrocyte antigen.
• FDP = fibrin degradation products.
• FFP = fresh frozen plasma.
• hIVIG = human IV immunoglobulin.
• IMHA = immune-mediated hemolytic 
anemia.
• MCV = mean cell volume.
• PT = prothrombin time.
• PTE = pulmonary thromboembolism.
• SLE = systemic lupus erythematosus.
Garden OA, Kidd L, Mexas AM, et al. 
ACVIM consensus statement on the 
diagnosis of immune-mediated hemolytic 
anemia in dogs and cats. J Vet Intern Med 
2019, 33(2):313–334.
Kohn B, Weingart C, Eckmann V, et al. 
Primary immune-mediated hemolytic 
anemia in 19 cats: diagnosis, therapy, and 
outcome (1998–2004). J Vet Intern Med 
2006, 20:159–166.
Swann JW, Garden OA, Fellman CL, et al. 
treatment of immune-mediated hemolytic 
anemia in dogs. J Vet Intern Med 2019, 
33(3):1141–1172.
Author  Bridget C. Garner
J. Catharine R. Scott-Moncrieff.
available online(continued)  Anemia, Immune-Mediated

86 Blackwell’s Five-Minute Veterinary Consult  
AAnemia, Iron-Deficiency
  BASICS
OVERVIEW
Caused by chronic external blood loss or 
iron-limited erythropoiesis.
• Fairly common in adult dogs, rare in adult 
cats.
• T ransient neonatal iron-deficiency anemia 
may occur at 5–10 weeks of age in kittens.
SIGNS
• Signs of anemia (e.g., lethargy, weakness, 
tachypnea, pale mucous membranes).
• Cardiovascular—bounding pulses, 
tachycardia, systolic heart murmur.
• Gastrointestinal—intermittent melena or 
hematochezia, diarrhea.
• Integumentary—heavy hematophagous 
parasite burden (e.g., fleas), wounds.
• Chronic external blood loss.
• Gastrointestinal—hookworms, lymphoma 
or other neoplasia, ulceration (related to 
medications, [e.g., non-steroidal anti-
inflammatories] or disease [e.g., renal disease]).
• Less common—severe flea infestation, 
urinary tract hemorrhage.
• Iatrogenic—blood donor overuse, excessive 
diagnostic blood sampling.
• Inappropriate home-cooked diet (low 
dietary iron).
  DIAGNOSIS
• Any cause of anemia, especially 
• Microcytic anemia in portosystemic shunt 
disease may or may not be due to iron deficiency.
• Anemia of inflammatory disease—iron-
limited erythropoiesis.
• Packed cell volume (PCV) variably 
decreased; may be within reference interval.
• Regenerative or nonregenerative anemia.
• Microcytosis—low normal or low mean cell 
volume (MCV), low mean reticulocyte 
volume (MCVr), anisocytosis, widened 
erythrocyte histogram, or increased red cell 
distribution width (RDW). Decreased mean 
cell hemoglobin concentration (MCHC) not 
sensitive or specific.
• Red blood cell (RBC) morphology—
microcytosis, hypochromia, keratocyte 
(indicating oxidative damage), and schistocyte 
formation.• Reticulocyte indices reticulocyte corpuscular 
hemoglobin concentration mean (CHCMr), 
reticulocyte hemoglobin content (CHr), 
hypochromic reticulocyte RBCs (%HYPOr), 
and %LowCHr are sensitive for detecting 
iron-limited erythropoiesis, but not specific.
• Lab tests indicating iron-limited erythro- 
poiesis do not differentiate true from 
functional iron deficiency. Clinical findings of 
inflammatory disease are required to differentiate 
iron-limited erythropoiesis. Inflammatory 
disease and true iron deficiency may also 
occur concurrently.
• Thrombocytosis due to chronic blood loss.
• Hypoproteinemia—from blood loss.
• Hypoferremia (serum iron <70  μg/dL) and 
transferrin saturation <15% support diagnosis.
• Serum iron values may be normal during 
iron repletion if blood loss is intermittent.
• Fecal exam for hookworms.
• Fecal examination for occult blood or 
melena.
IMAGING
abnormalities in gastrointestinal tract causing 
blood loss.
• Bone marrow aspirate, staining with Prussian 
blue (dogs only) to indicate body iron stores.
• Gastrointestinal endoscopy to identify sites 
of gastrointestinal blood loss.
  TREATMENT
• Identify/correct cause of blood loss, treat 
underlying disease.
• Administer iron until hematologic features 
of iron deficiency resolve.
• If severe anemia (i.e., PCV <15%), 
transfusion may be required, using whole 
blood (10–30 mL/kg IV) or packed RBC 
(10 mL/kg IV).
Parenteral Iron Supplementation
• Iron therapy should begin with injectable iron.
• Iron dextran—10–20 mg/kg IM (dog), 
50 mg IM (cat), followed by oral supple- 
Oral Iron Supplementation—Dogs Only
• Animals with severe iron deficiency may 
have impaired intestinal iron absorption, making oral therapy of little value until 
partial iron repletion has occurred.
• Oral iron supplementation should continue 
1–2 months, or until resolved.
• Ferrous sulfate powder—place in food or 
drinking water, 100–300 mg PO q24h.
• Ferrous gluconate—325 mg PO q24h.
• Oral iron is associated with unexplained 
death in kittens and should be avoided.
• Kittens undergo spontaneous iron 
replection beginning at 5–6 weeks of age.
  FOLLOW-UP
• Monitor CBC every 1–4 weeks, more 
frequently as needed.
• Effective treatment associated with an 
increase in MCV and reticulocyte volume.
• Erythrocyte histogram—effective treatment 
reduces microcytic subpopulation over time 
(2–3 months).
• CHCMr = mean reticulocyte corpuscular 
hemoglobin concentration.
• CHr = reticulocyte hemoglobin content.
• HYPOr = hypochromic reticulocyte 
RBCs.
• MCHC = mean cell hemoglobin 
• MCVr = mean reticulocyte volume.
• RDW = red cell distribution width.
Fry MM, Kirk CA. Reticulocyte indices in a 
canine model of nutritional iron deficiency. 
Vet Clin Pathol 2006, 35:172–181.
Radakovich LB, Santangelo KS, Olver CS. 
Reticulocyte hemoglobin content (CHr) 
does not differentiate true from functional 
iron deficiency in dogs. Vet Clin Pathol 
2015, 44:511–518.
Schaefer DM, Stokol T. The utility of 
reticulocyte indices in distinguishing iron 
deficiency anemia from anemia of inflam-
matory disease, portosystemic shunting, and 
breed-associated microcytosis in dogs. Vet 
Clin Pathol 2015, 44:109–119.
Authors  Glade Weiser and Melinda S. Camus

Canine and Feline, Seventh Edition  87
A Anemia, Nonregenerative
  BASICS
Low red blood cell (RBC) mass due to low 
erythroid production, without evidence of 
polychromasia or reticulocytosis in peripheral 
blood. Anemia with reticulocyte counts <80 × 
103/μL (dog) or 60 × 103/μL (cat) considered 
nonregenerative. Caused by altered erythro- 
poiesis or bone marrow injury.
• Alterations in erythropoiesis include 
deficient erythropoietin (EPO) production, 
nutritional deficiency, cytokine-mediated iron 
sequestration, disturbed metabolism in or 
destruction of RBC precursors (e.g., immune- 
mediated).
• Bone marrow injury usually caused by 
toxins, infection, or infiltrative processes.
• Anemia of inflammatory disease results 
from increased hepcidin production and 
release of cytokines from white blood cells 
(WBCs) leading to iron sequestration and 
decreased iron absorption. Low serum iron 
and transferrin, increased ferritin, decreased 
EPO production, shortened RBC lifespan 
result in anemia.
• Cardiovascular—shock from decreased 
systemic oxygen delivery.
• Hemic/lymph/immune.
• Hepatobiliary—from hypoxic injury.
• Nonregenerative immune-mediated 
hemolytic anemia (IMHA)—middle-aged 
female dogs and male cats <3 years old.
• Congenital cobalamin malabsorption 
reported in Komondor, beagle, giant 
schnauzer, Australian shepherd, border collie, 
shar-pei.
SIGNS
Usually secondary; signs associated with 
primary disease often precede signs of 
anemia.
• Lethargy, exercise intolerance, inappetence, 
pica.
• Other findings reflect primary condition—
polyuria/polydipsia (chronic kidney disease 
[CKD]), old paint exposure (lead poisoning), 
estrogen therapy or feminization in male 
dogs, failure to thrive (hereditary cobalamin 
malabsorption).
• Pallor, heart murmur (due to anemia), 
tachycardia, tachypnea, shock.
• Digital rectal examination may reveal 
melena if gastrointestinal (GI) blood loss.• Signs reflecting primary condition—oral 
ulcerations (CKD), cachexia, organomegaly, 
GI or nervous system abnormalities (cobalamin 
malabsorption, lead poisoning), symmetric 
alopecia (hypothyroidism, hyperestrogenism).
CAUSES
Nonregenerative Anemia without Other 
Cytopenias
• Anemia of inflammatory disease (AID)—
most common cause of mild nonregenerative 
anemia (also anemia of chronic disease).
• CKD—decreased EPO production by 
kidneys; uremic toxins shorten RBC lifespan 
and impair bone marrow response to EPO.
• Chronic liver disease—shortened RBC 
survival due to changes in RBC membrane 
lipids; functional iron deficiency due to 
decreased transferrin synthesis and impaired 
mobilization of hepatic iron.
• Hypothyroidism, hypoadrenocorticism—
thyroid hormones and cortisol stimulate 
erythropoiesis.
• Immune-mediated destruction of precursors—  
spectrum from nonregenerative IMHA to 
pure red cell aplasia.
Nutritional or Mineral Deficiency/Toxicity
• Iron deficiency—usually due to chronic 
external blood loss.
• Copper deficiency—secondary to chelation 
therapy.
• Cobalamin (vitamin B12) and/or folate 
deficiency—rare; can be caused by dietary 
insufficiency, malabsorption, congenital 
defects in cobalamin absorption.
• Disruption of precursor metabolism—
chronic lead toxicity and possibly high 
concentrations of aluminum, arsenic, and 
cadmium inhibit heme synthesis; cadmium 
and lead cause renal toxicity, impaired EPO 
production.
Nonregenerative Anemia with Other 
• Toxicities—drugs or chemicals, hormones 
(e.g., estrogen).
• Infections—feline leukemia virus (FeLV), 
feline immunodeficiency virus (FIV), 
ehrlichiosis, babesiosis, Cytauxzoon felis , 
parvovirus (occasionally just erythroid line 
affected).
• Infiltrative processes—myelodysplasia, 
myeloproliferative and lymphoproliferative 
diseases, histiocytic sarcoma, metastatic 
neoplasia, myelofibrosis, osteosclerosis.
• CKD.
• Inflammatory or chronic disease.
• Multicat household/cattery (infectious 
disease risk).
• Daily exposure to toxins (e.g., old homes with 
lead paint, environmental pollution).  DIAGNOSIS
Regenerative anemia can initially appear 
nonregenerative (especially in cats); exacerba-
tion of chronic condition may produce 
appearance of acute onset.
CBC and Blood Smear
• Packed cell volume (PCV), hematocrit 
(HCT), RBC count, and hemoglobin 
concentration low.
• Anemia usually normocytic, normochromic, 
with normal mean cell volume (MCV) and 
mean corpuscular hemoglobin concentration 
(MCHC); occasionally severe vitamin B12 
deficiency; characteristic large erythrocytes 
can be masked by presence of misshapen and/
or small RBCs, giving normal MCV but 
widened red cell distribution.
• Macrocytosis (high MCV)—without 
polychromasia suggests nuclear maturation 
defect; seen in cats with FeLV.
• Microcytosis suggests maturation complete; 
iron deficiency most common cause; in late 
stages concurrent hypochromasia common 
in dogs.
• Characteristic RBC morphologies—
schistocytes ± hypochromic RBCs common 
with iron deficiency; acanthocytes with liver 
disease; target cells with iron deficiency, liver 
disease, hypothyroidism.
• Inflammatory leukogram supports AID.
• Thrombocytosis common in iron deficiency.
• High number of nucleated red blood cells 
(NRBCs) without polychromasia or 
disproportionate to degree of anemia and 
polychromasia seen with lead toxicity, 
extramedullary hematopoiesis (EMH), heat 
stroke, bone marrow injury.
• RBC or WBC precursors in peripheral 
blood without orderly progression to more 
mature forms suggest myelodysplasia or 
myeloproliferative disease.
• Cobalamin malabsorption characterized by 
normocytic anemia, neutropenia, hypersegmented 
neutrophils; megaloblastic changes possible 
in marrow.
• RBC inclusions may be visible on blood smear 
with some infectious diseases (e.g., C. felis ).
Serum Biochemistry and Urinalysis
• CKD—azotemia with isosthenuria, possible 
proteinuria, hypokalemia.
• Liver disease—elevated alanine aminotrans -
ferase (ALT) ± alkaline phosphatase (ALP) 
activities, elevated total bilirubin, bile acids, 
ammonia concentrations, hypoglycemia, 
hypoalbuminemia.
• Hypothyroidism—hypercholesterolemia 
(>500 mg/dL).

88 Blackwell’s Five-Minute Veterinary Consult  
A
hyperkalemia, lymphocytosis, eosinophilia.
• Reticulocyte count.
• Spherocytosis, autoagglutination, or 
positive Coombs’ test supports immune-
mediated destruction of erythroid precursors.
• Serum iron profile—with iron deficiency 
both serum iron and ferritin low, while total 
iron-binding capacity varies; with AID, serum 
iron low but serum ferritin high.
• Serum lead—indicated when NRBCs 
present; >30 μL/dL (0.3 ppm) strongly 
supports lead intoxication.
• Serologic testing—FeLV, FIV in cats; 
Ehrlichia canis , Anaplasma phagocytophilia  in 
dogs, particularly if anemia with thrombo- 
cytopenia.
• Endocrine testing—adrenocorticotropic 
hormone (ACTH) stimulation test or 
thyroid function testing to rule out 
hypoadrenocorticism or hypothyroidism, 
respectively.
• Serum cobalamin, homocysteine, methyl- 
malonic acid ± urine methylmalonic acid 
concentrations—to diagnose hereditary 
cobalamin malabsorption.
Cytologic Examination of Bone Marrow 
and Core Biopsy
• Cytologic examination of bone marrow 
aspirate indicated in all patients unless 
primary cause apparent, and bone marrow 
core biopsy useful in evaluation of bone 
marrow architecture and overall cellularity.
• Erythroid hypoplasia or aplasia confirms 
pure red cell aplasia; erythroid hyperplasia 
suggests IMHA; increased erythrophagia or 
incomplete maturation sequence suggests 
immune-mediated or toxic injury to specific 
maturation stage, or incomplete recovery 
from previous injury.
• Expanded erythron and high numbers of 
metarubricytes suggest iron deficiency; 
absence of iron stores supportive in dogs, but 
not cats.
• Disorderly maturation and atypical cellular 
morphology suggest myelodysplastic syndrome.
• Hypercellular marrow with increased blast 
cells consistent with hematopoietic neoplasia; 
immunophenotyping can identify affected 
cell line.
• Hypocellular sample can suggest aplastic 
marrow or myelofibrosis.
Abdominal Radiographs, Ultrasound
As part of evaluation for underlying causes 
such as neoplasia, CKD, or GI blood loss.  TREATMENT
• Anemia usually resolves with resolution of 
• Conditions associated with severe anemia 
or pancytopenia often carry guarded to poor 
prognosis and may involve long-term 
treatment with incomplete resolution.
• Mild to moderate anemia (PCV >20%) 
generally requires no immediate supportive 
intervention.
• Patients with severe anemia (PCV <12–15%) 
require transfusion for stabilization (e.g., 
6–10 mL/kg packed RBCs or 10–20 mL/kg 
whole blood).
• Determine blood type prior to transfusion 
(imperative for cats, ideal for dogs).
• If blood volume and tissue perfusion 
compromised by concurrent blood loss or 
shock, administer isotonic crystalloid solution 
(10–20 mL/kg IV, repeat as necessary) or 
isotonic colloid solution (2–5 mL/kg IV, to 
total 20 mL/kg/24h). See Shock, Hypovolemic.
• With chronic anemia, animals may be 
hypervolemic, and volume overload may be a 
concern during blood and fluid therapy.
• EPO or darbopoetin in patients with 
• Iron supplementation in patients with iron 
deficiency anemia.
• Immunosuppressive drugs.
• May supplement with cobalamin (vitamin 
B12) at rate of 100–200 mg PO q24h (dogs) 
or 50–100 mg PO q24h (cats); parenteral 
cyanocobalamin administration (50  μg/kg 
SC/IM weekly to monthly) needed in dogs 
with inherited cobalamin malabsorption.
Monitor for transfusion reactions.
  FOLLOW-UP
• With severe anemia—serial physical 
examinations, PCV/CBC, blood smear 
examination every 1–2 days.
• Stable animals with chronic or slowly 
improving disease course—reevaluate every 
1–2 weeks.  MISCELLANEOUS
Pregnant animals have mildly low PCV.
SEE ALSO
• Anemia, Immune-Mediated.
• Anemia, Iron-Deficiency.
• Blood T ransfusion Reactions.
• Shock, Hypovolemic.
• AID = anemia of inflammatory disease.
• EMH = extramedullary hematopoiesis.
• HCT = hematocrit.
anemia.
• NRBC = nucleated red blood cell.
Hohenhaus, AE, Winzelberg SE. 
Nonregenerative anemia. In: Ettinger SJ, 
Feldman EC, eds., Textbook of Veterinary 
Internal Medicine: Diseases of the Dog and 
Cat, 8th ed. St. Louis, MO: Elsevier 
Saunders, 2017, pp. 838–843.
Rebar AH, MacWilliams PS, Feldman BF , 
et al. Erythrocytes: overview, morphology, 
quantity. In: A Guide to Hematology in 
Dogs and Cats, Jackson, WY: Teton 
NewMedia. http://www.ivis.org/advances/
Rebar/Chap4/chapter.asp?LA=1
Author  Joyce S. Knoll
Consulting Editor  Melinda S. CamusAnemia, Nonregenerative  (continued)

Canine and Feline, Seventh Edition  89
A Anemia, Nuclear Maturation Defects (Anemia, Megaloblastic)
  BASICS
OVERVIEW
• Nonregenerative anemia characterized by 
impaired DNA synthesis in red blood cell 
(RBC) precursors (nuclear : cytoplasmic 
asynchrony).
• Affected RBC precursors fail to divide 
normally and thus are larger than corresponding 
normal precursors; their nuclei are deficient 
in chromatin with open and stippled 
appearance; these giant precursors with 
atypical nuclei are known as megaloblasts. 
Hemoglobin content in these precursors is 
normal.
• Asynchronous changes most prominent in 
RBC precursors, but white blood cell (WBC) 
and platelet precursors similarly affected.
• Cats—often associated with feline leukemia 
virus (FeLV) infection.
• Dogs—usually acquired, but may be 
inherited.
• Breed predilection for inherited cobalamin 
malabsorption—giant schnauzers, Australian 
shepherds, Komondorok, and beagles—
present as young as 8–12 weeks; border 
collies as young adults.
• Familial macrocytosis and megaloblastic 
change in toy/miniature poodles.
SIGNS
• In dogs, anemia often not symptomatic. 
For cobalamin deficiency, clinical signs 
include gastrointestinal signs and failure to 
thrive. Affected poodles usually not anemic.
• In cats, anemia may be mild to marked, if 
FeLV positive.
• Infectious—FeLV most common cause in 
cats. Feline immunodeficiency virus (FIV) 
infrequently reported as causative agent.
• Nutritional—folic acid and cobalamin 
deficiencies, primarily in dogs with inherited 
cobalamin malabsorption (uncommon with 
other causes of cobalamin deficiency).
• Toxic—many drugs such as immuno­
modulators, chemotherapeutic agents, 
anticonvulsants, antibiotics.
• Congenital—toy/miniature poodles.
  DIAGNOSIS
• In dogs, all other mild to moderate 
nonregenerative anemias, including anemia of 
inflammatory disease and lead poisoning.• Differentiation based on distinctive CBC 
and bone marrow findings.
• In cats, FeLV infection is primary 
differential.
• Classically, anemia macrocytic and 
normochromic, but often normocytic.
• Large, fully hemoglobinized RBC; few to 
many nucleated RBC precursors, no 
polychromasia.
• In dogs, mild to moderate anemia; may 
see neutropenia with hypersegmented 
neutrophils.
• In cats, mild to marked anemia.
• In cats with FeLV, anemia may occur with 
myelodysplastic syndrome or leukemia.
• In dogs with inherited cobalamin 
malabsorption, can see proteinuria and 
variable biochemistry derangements.
• FeLV in blood and bone marrow.
• Genetic tests for dogs with inherited 
cobalamin malabsorption (available at 
University of Pennsylvania, PennGen).
• Serum cobalamin.
• Methylmalonic acid (MMA) in serum or 
urine (increase caused by inhibited cobalamin ­ 
dependent enzyme).
IMAGING
N/A
Bone Marrow Biopsy
• In dogs, usually hyperplastic; may be 
hypocellular with hemosiderosis.
• In cats, may be hypo ­ or hyperplastic.
• Maturation arrest with nuclear : cytoplasmic 
asynchrony possible in all cell lines.
• Megaloblastic RBC precursors.
• Macrophage hyperplasia with phagocytosis 
of nucleated RBCs.
  TREATMENT
• Anemia often mild and does not need 
specific therapy. FeLV ­positive cats may 
require blood transfusion for stabilization.
• Target underlying cause and address 
concurrent signs.
• In animals with drug toxicity, discontinue 
offending drug.• In animals with hypocobalaminemia, 
supplement with vitamin B12 (0.25–1 mg 
cyanocobalamin SC weekly to monthly or 
hydroxycobalamin IM every few months; 
oral may be effective in some patients— 
dogs, 250–1000  μg/day PO; cats,  
250 μg/day PO).
Avoid drugs known to cause megaloblastic 
anemia in patients whose condition results 
from other causes.
  FOLLOW-UP
• Monitor response to treatment by CBC 
(weekly to every few months).
• Closely monitor FeLV ­positive cats for 
disease progression.
• Prognosis depends on underlying cause; 
in FeLV ­positive cats, prognosis poor; with 
drug­induced anemia, prognosis good if 
drug discontinued; inherited cobalamin 
malabsorption has good prognosis, with 
lifelong cobalamin supplementation.
SEE ALSO
• Anemia, Nonregenerative.
• Feline Leukemia Virus (FeLV) Infection.
• MMA = methylmalonic acid.
Harvey JW. Veterinary Hematology: A 
Diagnostic Guide and Color Atlas. Beijing: 
Elsevier, 2012, pp. 273–275.
et al. A Guide to Hematology in Dogs and 
Cats. Jackson, WY: Teton NewMedia, 2002, 
pp. 57–58.
Weiss, DJ. Congenital dyserythropoiesis. In: 
Weiss DJ, Wardrop KJ, eds., Schalm’s 
Veterinary Hematology, 6th ed. Ames, IA: 
Wiley ­Blackwell, 2010, pp. 196–198.
Author  Lisa S. Kelly
Alan H. Rebar.

90 Blackwell’s Five-Minute Veterinary Consult  
AAnemia, Regenerative
  BASICS
Decreased circulating red blood cell (RBC) 
mass (indicated by low packed cell volume 
[PCV] or hematocrit [HCT], hemoglobin, 
and total RBC count) accompanied by 
appropriate, compensatory increase in RBC 
production by the bone marrow.
• Caused by blood loss or hemolysis.
• Hemolysis—caused by intrinsic RBC 
defects (e.g., congenital RBC membrane 
defects or enzyme deficiencies) or extrinsic 
factors (e.g., RBC parasites, oxidative injury, 
hemolysins, osmotic changes, immune-
mediated RBC destruction, hemophagocytic 
neoplasia, heat stroke, and severe hypophos- 
phatemia).
• Cardiovascular—murmurs with marked 
anemia; tachycardia.
• Hemic/lymph/immune—erythroid 
hyperplasia in bone marrow; splenic 
extramedullary hematopoiesis (EMH).
• Hepatic—decreased oxygen delivery causes 
centrilobular degeneration of liver.
• Renal—severe intravascular hemolysis rarely 
leads to pigmentary nephropathy and acute 
• Musculoskeletal—progressive osteoclerosis 
seen in pyruvate kinase (PK)-deficient dogs.
• PK deficiency—basenji, beagle, cairn 
terrier, Chihuahua, dachshund, Labrador 
retriever, labradoodle, miniature poodle, pug, 
West Highland white terrier, and American 
Eskimo; Somali, Abyssinian, domestic 
shorthair cats.
• PFK deficiency—Australian labradoodle, 
English springer spaniel, American cocker 
spaniel, cockapoo, English cocker spaniel, 
whippet, wachtelhund, and mixed breed dogs 
with spaniel parentage.
• Marked RBC osmotic fragility—English 
springer spaniel; Abyssinian, Somali, Siamese, 
and domestic shorthair cats.
• Feline congenital porphyria—Siamese and 
domestic shorthair cats.
• Heritable coagulopathies (e.g., factor VIII 
or IX deficiency), von Willebrand disease.
• Immune-mediated hemolytic anemia 
(IMHA)—middle-aged female dogs, especially 
American cocker spaniels, English springer 
spaniels, Irish setters, Old English sheepdogs, 
poodles, and Shetland sheepdogs.
• Hemophagocytic histiocytic sarcoma—
Bernese mountain dog, Rottweiler, golden 
retriever, and flat-coated retriever.SIGNS
• Pallor.
• Weakness, exercise intolerance, collapse.
• Possible heart murmur, tachycardia, 
bounding pulses (unless hemorrhage is 
present).
• Possible jaundice and hemoglobinuria.
• Petechiae, epistaxis, melena suggest blood 
loss due to vasculitis or thrombopathia.
• Hematomas or cavity bleeds suggest 
coagulation factor inhibition or deficiency.
• Clinical signs depend on degree of anemia 
and rapidity of onset.
• Rapid loss of 15–25% blood volume or 
acute hemolysis results in shock.
• With chronic anemia, compensatory 
increases in heart rate, and eventually heart 
size, occur; hemoglobin can drop to as low as 
50% of minimum normal value without overt 
signs of shock or decreased oxygen delivery.
CAUSES
• Immune-mediated (IMHA).
• RBC toxins—snake venom and bee stings 
may cause RBC hemolysis; oxidants can cause 
Heinz body formation.
• Erythrocyte parasites—cats: Mycoplasma  
spp., Cytauxzoon felis  (may be nonregenerative); 
dogs: Mycoplasma haemocanis , Babesia  spp.
• Mechanical RBC fragmentation—caused 
by vasculitis, thromboembolic disease, or 
disease of any vascular organ; rare cause of 
significant anemia unless accompanied by 
• Inherited RBC abnormalities:
 ∘PK deficiency.
 ∘Phosphofructokinase (PFK) deficiency.
 ∘Increased RBC osmotic fragility (unknown 
RBC defect), leads to recurrent severe anemia 
and splenomegaly.
 ∘Feline congenital porphyria—enzyme 
deficiency in heme synthetic pathway leads to 
accumulation of heme precursors, hemolytic 
anemia, and brown-red discoloration of teeth 
and bones; Siamese tend to have severe 
hemolytic anemia, while domestic shorthair 
cats have less severe autosomal dominant trait 
that causes mild anemia.
• Hypophosphatemia—severe hypophospha -
temia impairs adenosine triphosphate (ATP) 
production, leading to increased erythrocyte 
fragility and hemolysis; seen with refeeding 
syndrome and insulin administration.
• Blood loss:
 ∘T rauma.
 ∘Bleeding neoplasms.
 ∘Coagulopathies (e.g., warfarin toxicity, 
hemophilia, thrombocytopenia).
 ∘Blood-feeding parasites.
 ∘Gastrointestinal ulcers.  DIAGNOSIS
Differentiated from nonregenerative anemia 
by a reticulocyte count above the regenerative 
threshold for that species, generally above 
80 × 103/μL in dogs and 60 × 103/μL in cats.
Results
• Lipemia can cause mild in vitro hemolysis, 
without appreciable anemia, and may falsely 
elevate mean corpuscular hemoglobin 
concentration (MCHC).
• Autoagglutination may falsely decrease 
RBC count and increase MCV.
• Exercise and excitement can increase RBC 
count, PCV, and reticulocyte count through 
splenic contraction, masking severity of anemia.
Valid If Run in Human Laboratory?
• Dogs—yes.
• Cats—yes, if hematology instrument uses 
species-specific parameters; instruments 
designed for analysis of human specimens 
may undercount small feline RBCs and be 
unable to distinguish between erythrocytes 
and platelets.
• PCV, RBC count, and hemoglobin are 
below the reference interval.
• Total protein is often low with blood loss 
anemia and may be the only sign with acute 
blood loss due to splenic contraction, which 
elevates the circulating RBC count.
• RBC indices vary depending on the cause of 
anemia and degree of regenerative response:
 ∘Mean cell volume (MCV) is normal to 
high with regeneration, but low with iron 
deficiency.
 ∘MCHC is normal to low in most 
patients, low with iron deficiency, and 
artificially high with hemolysis.
• Specific RBC morphologies may suggest 
the cause of hemolysis:
 ∘Marked spherocytosis suggests immune-
mediated disease in dogs.
 ∘Heinz bodies or eccentrocytes suggest 
oxidant injury.
 ∘Numerous schistocytes suggest 
microangiopathy.
 ∘RBC parasites may be found on or within 
RBC.
• Agglutinated RBCs indicate anemia is 
immune mediated; distinguish autoaggluti -
nation from rouleaux by saline agglutination 
test (see Appendix X).
• Hemolysis is often accompanied by an 
inflammatory leukogram.

Canine and Feline, Seventh Edition  91
A
• Animals with IMHA often have a 
concurrent thrombocytopenia, while iron 
deficiency is often accompanied by thrombo- 
cytosis.
• Hyperbilirubinemia and bilirubinuria 
accompany marked hemolysis; hemoglobin- 
emia and hemoglobinuria can be seen 
following intravascular hemolysis.
• Reticulocytosis may be absent in the first 
3–5 days after onset of blood loss or hemolysis.
• Direct antiglobulin test (Coombs’ test) is 
indicated when IMHA is suspected, in the 
absence of agglutination; a positive test is 
confirmatory.
• The rapid osmotic fragility test detects 
erythrocyte membrane defects and can help 
to discriminate hemolytic from nonhemolytic 
• Coagulation testing may be indicated in 
cases of blood loss.
• PCR is more sensitive for diagnosis of 
Babesia  and hemotropic Mycoplasma  than 
microscopic blood smear exam; can 
differentiate between species.
• PCR for PK deficiency.
• PCR for PFK deficiency.
Fine-needle aspiration and cytologic exam of 
abnormal spleen, lung, or lymph nodes may 
help to diagnose hemophagocytic histiocytic 
sarcoma.
  TREATMENT
• Emergency if anemia is severe or has 
developed rapidly.
• Massive hemorrhage leads to hypovolemic 
shock and decreased oxygen delivery to 
tissues; acute hemolysis also leads to decreased 
oxygen content in the blood.
• In cases of massive hemorrhage, crystalloid 
fluids can rapidly correct hypovolemia and 
restore circulation, but RBC replacement 
(and resolving the source of hemorrhage) is 
necessary for definitive therapy.• RBC replacement (packed RBCs or whole 
blood) indicated with severe anemia (PCV 
<15%) or rapid drops (>15%) in HCT. 
Initial dosage depends on product selected; 
1 mL/kg of packed RBCs will raise the HCT 
by approximately 1%; 3 mL/kg of whole 
blood will raise the PCV by approximately 
1%, both depending on the PCV of the 
donor product.
• In cases of hemorrhage or coagulopathy, 
fresh whole blood will also provide volume 
expansion and coagulation factor replacement, 
compared to packed RBCs.
• Determine blood type prior to transfusion, 
especially in cats (who have preexisting 
autoantibodies to opposite blood types). 
Cross-match against donor blood if blood 
typing reagents not available, or if patient 
requires second transfusion more than 4 days 
after first transfusion.
• Animals with chronic blood loss or 
hemolytic anemias are generally normovolemic 
with increased cardiac output, therefore 
attention should be paid to transfusion 
volumes and rates.
• Iron may benefit animals with chronic 
blood-loss anemia (see Anemia, Iron- 
Deficiency).
• Hemolytic anemias—varies with cause of 
hemolysis.
  FOLLOW-UP
• Initially, monitor PCV and morphologic 
features of RBCs on a blood smear every 24 
hours to evaluate effectiveness of treatment 
and bone marrow responsiveness; polychrom- 
asia may be seen as regenerative response 
starts.
• As regeneration becomes apparent, recheck 
every 3–5 days.• During and following transfusion, monitor 
for transfusion reactions (see Blood T ransfusion 
Reactions).
SEE ALSO
• Anemia, Heinz Body.
• Babesiosis.
• Bartonellosis.
• Cytauxzoonosis.
• Phosphofructokinase Deficiency.
• Pyruvate Kinase Deficiency.
• Von Willebrand Disease.
• ATP = adenosine triphosphate.
anemia.
• PFK = phosphofructokinase.
• PK = pyruvate kinase.
Piek C. Immune-mediated haemolytic 
anemia and other regenerative anemias. 
In: Ettinger SJ, Feldman EC, eds., 
Textbook of Veterinary Internal Medicine: 
Diseases of the Dog and Cat, 8th ed. St. 
Louis, MO: Elsevier Saunders, 2017, 
pp. 829–837.
Consulting Editor  Melinda S. Camus(continued)  Anemia, Regenerative

92 Blackwell’s Five-Minute Veterinary Consult  
AAnisocoria
  BASICS
Asymmetric pupils.
• Disruption of sympathetic (causing miosis) 
or parasympathetic (causing mydriasis) 
innervation to the eye.
• Ocular disease—numerous causes.
• Nervous.
• Ophthalmic.
GENETICS
None
Common
• All ages affected.
• No gender predisposition.
SIGNS
Unequal pupil size.
CAUSES
Neurologic
See Table 1.
Ocular
See Table 2.
N/A
  DIAGNOSIS
• Must determine which pupil is abnormal—
see Figure 1 and Tables 1 and 2.• Distinguish between neurologic and ocular 
causes.
N/A
N/A
IMAGING
• See Table 1.
• Ultrasound—use to identify ocular, 
retrobulbar, or jugular groove lesions.
• MRI—use to identify CNS lesions.
• CT—use to identify tympanic bulla lesions.
• Cerebral spinal fluid (CSF) tap—evaluate 
for CNS inflammation/infection.
• ERG—evaluate retinal function.
• Pharmacologic testing—see Figure 1; 
postganglionic lesions cause denervation 
supersensitivity, resulting in more rapid 
constriction or dilation with application of 
Table 1
Neurologic lesions causing anisocoria.
Sign Pupillary Light 
Reflex (PLR)Lesion Localization Differential List Diagnostic Test
Mydriasis—inability to 
constrict the pupilNo direct, present 
indirectIpsilateral optic nerve/chiasm Neuritis, neoplasia
Encephalitis, neoplasia, trauma, 
retrobulbar massMRI/CSF tap/ERG
MRI/CSF tap
Ultrasound orbit
Miosis—inability to 
dilate the pupilPresent Brainstem
C1-T2 myelopathy or C6-T3 
brachial plexus
Vagosympathetic trunk
Tympanic bulla
Trigeminal nerveEncephalitis, neoplasia, trauma
Trauma, myelitis, neoplasia, intervertebral 
disc herniation (IVDH; rare)
Jugular venipuncture, trauma
Otitis media, neoplasia, trauma
Neuritis, neoplasiaMRI/CSF tap
MRI/myelogram/CT
MRI/ultrasound
MRI/CT
MRI
Table 2
Ocular diseases causing anisocoria.
Lesion Associated Signs Causes
Anterior uveitis Miosis, aqueous flare, corneal edema, conjunctival hyperemia Infectious/inflammatory disease, trauma, neoplasia
Glaucoma Mydriasis
Sluggish/absent PLR, increased intraocular pressure, corneal edemaPrimary glaucoma, secondary glaucoma
Neoplasm
Posterior synechia
Iris atrophy
Iris hypoplasia
Pharmacologic 
blockadeMiosis/mydriasis, iris color change
Variable pupil shape, sluggish/absent PLR, anterior uveitis
Variable pupil shape, iridal thinning, sluggish PLR
Sluggish/absent PLR, irregular pupil margin, other ocular abnormalities
Mydriasis
Absent direct/consensual PLR
Normal visionLymphoma, melanoma
Secondary to anterior uveitis
Old age change
Atropine
Spastic pupil syndrome Miosis, normal vision Feline leukemia virus

Canine and Feline, Seventh Edition  93
A
Anisocoria
Intact direct and indirect PLRMiotic pupil in the dar k
SYMPATHETIC DYSFUNCTIO N
1% hydroxyamphetamine
Dilatio n
Normal eye 
or pre 
ganglionic 
lesion
Evaluate for 
central 
(spinal cord 
or brain), 
brachial  
plexus or  
vago-
sympathetic 
trunk lesionNo dilation
Post 
lesion
Evaluate 
tympanic 
bulla or  
trigeminal 
nerve1% phenylephrine
No dilation
Normal Dilatio n
Abnormal ey e
Evaluate central, 
brachial plexus, 
vagosympathetic
trunk, bulla and 
trigeminal nerveIncomplete or absent PLRPupils dilated and equal in dark
PARASYMPATHETIC 
DYSFUNCTION
0.5%  
physostigmin e
Delayed  
constriction
NormalNo 
Post 
ganglionic
Lesion in 
the iris or 
oculomotor
nerveRapid  
Preganglionic
brainstem 
or 
nerve 
disease0.2%  
pilocarpin e
No 
Iris atroph yRapid  
Constrictio n
lesion of the 
iris, 
nerve or  
brainste mNo 
constrictio n
Normal
Figure 1 .
pharmacologic agents. Differentiation of 
pre- or postganglionic lesions can be 
difficult if based solely on pharmacologic 
testing.
Dependent on underlying diagnosis.
  TREATMENT
Dependent on underlying disease.
N/A
N/A
N/A
N/A
N/A
N/A
Depends on underlying disease.
N/A
N/A
N/A
N/A
SYNONYMS
NoneSEE ALSO
• Anterior Uveitis—Cats.
• Anterior Uveitis—Dogs.
• Glaucoma.
• Horner’s Syndrome.
• Iris Atrophy.
• Optic Neuritis and Papilledema.
• CSF = cerebrospinal fluid.
• IVDH = intervertebral disc herniation.
• PLR = pupillary light reflex.
Cottrill NB. Differential diagnosis of 
anisocoria. In: Bonagura J, T wedt D, eds., 
Kirk’s Current Veterinary Therapy, 14th ed. 
St. Louis, MO: Saunders, 2009, pp. 
1168–1174.
Lorenz MD, Kornegay JN. Blindness, anisocoria 
and abnormal eye movements. In: Lorenz 
MD, Kornegay, JN, eds., Handbook of 
Veterinary Neurology, 4th ed. St. Louis, 
MO: Saunders, 2004, pp. 283–295.
Author  Heidi L. Barnes Heller
Consulting Editor  Kathern E. Myrna
available online(continued)  Anisocoria

94 Blackwell’s Five-Minute Veterinary Consult  
AAnorexia
  BASICS
Anorexia is the lack or loss of appetite for 
food. Hyporexia is a reduction in appetite, 
while dysrexia is a change in appetite or lack 
of consistent appetite. Anorexia results in 
decreased food intake, which then leads to 
weight loss, dehydration, nutritional 
deficiencies, and/or sarcopenia.
• The control of appetite is a complex 
interaction between the central nervous system, 
the environment, and the gastrointestinal (GI) 
tract. • The hypothalamus and brainstem 
contain feeding‐regulatory neurons that act as 
input stations for sensory and metabolic signals. 
These cell populations project to several brain 
regions and interconnect extensively. • Sensory 
signals that affect appetite include the odor, 
taste, texture, and temperature of food, as well 
as gastric and duodenal distention. • Metabolic 
signals for hunger and satiety include a variety 
of peptides and hormones released during the 
fasting and fed states, as well as plasma 
concentrations of glucose, amino acids, and 
fatty acids. • Insulin, glucagon, somatostatin, 
cholecystokinin, peptide tyrosine tyrosine 
(PYY), and pancreatic peptide decrease hunger 
centrally. • Leptin, produced primarily by 
adipocytes, acts on specific hypothalamic 
receptors to increase metabolism and decrease 
appetite. • Neuropeptide Y, released from the 
GI tract after food restriction, induces hunger 
and decreases energy expenditure. • Ghrelin, 
produced by the stomach, is a prokinetic and 
increases appetite; it decreases leptin and 
increases neuropeptide Y production. 
• Serotonin is an important central mediator 
and acts via a serotonergic tract that passes near 
the ventromedial hypothalamic nuclei (satiety 
center). • Dopaminergic tracts in the hypo-  
thalamus help regulate food intake and are 
closely associated with the lateral hypothalamic 
nuclei (feeding center). • Environmental 
factors including the location and timing of 
meals, as well as learned behaviors and circadian 
rhythms, modulate appetite. • Brain lesions 
that affect the hypothalamus can decrease or 
increase appetite; any disorder that decreases 
cerebral arousal will potentially decrease food 
intake. • Inflammatory and neoplastic diseases 
can cause hyporexia by the release of proinflamm  - 
atory cytokines. • The expected upregulation 
of dietary intake in response to increased energy 
expenditure is frequently absent in patients 
with neoplastic and advanced cardiac diseases. 
• Exogenous and endogenous toxins (e.g., renal 
and liver failure) cause hyporexia. • Neoplasia, 
metabolic disorders, pancreatitis, and primary 
GI diseases are associated with hyporexia. 
• Fear, pain, and stress may decrease appetite.SYSTEMS AFFECTED
All body systems.
GENETICS
N/A
Unknown
N/A
Species
N/A
N/A
N/A
SIGNS
• Refusal to eat is a common presenting 
complaint and causes owners significant 
distress. • Weight loss may be reported.
• Findings vary depending on the underlying 
cause. • Low body condition score and 
muscle wasting may be evident depending 
upon the duration of decreased food intake. 
• Pseudoanorectic patients commonly display 
halitosis, excessive drooling, difficulty with 
prehension or mastication, and odynophagia 
(painful swallowing).
CAUSES
Anorexia/Hyporexia/Dysrexia
• Possible manifestations of a myriad of systemic 
disorders. • Psychological—food aversion, stress, 
alterations in routine or environment. • Pain. 
• Toxicities and drug adverse effects. • GI and 
pancreatic diseases. • Acid‐base disorders. 
• Organ failure—e.g., cardiac, renal, hepatic. 
• Endocrine and metabolic diseases. • Neoplasia. 
• Infectious diseases. • Immune‐mediated 
diseases. • Respiratory diseases. • Musculo -
skeletal diseases. • Neurologic diseases. 
• Miscellaneous (e.g., motion sickness, high 
environmental temperature).
Pseudoanorexia
Any disease causing painful or dysfunctional 
prehension, mastication, or swallowing.
N/A
  DIAGNOSIS
• Pseudoanorexia is a term describing patients 
who are hungry but are unable to eat due to 
disorders causing dysfunction or pain of the 
face, neck, oropharynx, and esophagus. • Animals lacking a sense of smell (anosmia) 
often show a lack of interest in food.
• Abnormalities vary with different 
underlying diseases. • May be normal.
• Additional diagnostic tests may be necessary 
to investigate specific diseases suggested by 
history, physical examination, and preliminary 
tests. • Heartworm serology, tick serology, 
retrovirus serology, thyroid level, and histologic/
cytologic examination of tissue/cell samples 
may be required to make a definitive diagnosis. 
• A baseline cortisol or an adrenocorticotropic 
hormone (ACTH) stimulation test to rule out 
hypoadrenocorticism is warranted even when 
there are no significant laboratory changes.
IMAGING
• Thoracic and abdominal imaging 
(radiographs and ultrasound) studies are often 
included in the minimum database to detect 
anatomic or functional abnormalities. 
• Videofluoroscopy and endoscopy may be 
indicated to specifically evaluate pharyngeal, 
esophageal, and GI function and appearance.
• Perform a nutritional assessment; collect a 
thorough dietary history, evaluate food intake, 
and obtain body and muscle condition scores. 
• Elicit a thorough history regarding the 
patient’s environment, changes in routine, 
people, or other pets, to help identify 
potential sources of psychologic stress. 
• Observe the patient’s interest in food and 
ability to prehend, masticate, and swallow 
food. • Complete a thorough physical 
examination including ophthalmic, 
oropharyngeal, neurologic, orthopedic, 
thoracic, abdominal, and rectal exam to 
determine the presence of disease.
  TREATMENT
• Assisted feeding (enteral and/or parenteral 
feeding) should be considered immediately 
for significantly malnourished patients (≥10% 
body weight loss, hypoalbuminemia, poor 
body condition score, evidence of muscle 
wasting, and/or chronic disease processes). In 
well‐conditioned patients with decreased 
appetite, assisted feeding should be considered 
if food consumption is less than the resting 
energy requirement [RER = 70 x (body 
weightkg 0.75)] for 3–5 days without trends 
toward improvement. • Force feeding should 
be avoided, particularly in cats, considering 
the association with conditioned food 
aversions.

Canine and Feline, Seventh Edition  95
A
• Medications the patient is receiving should be 
reviewed for possible side effects leading to 
reduced appetite. • Provide comfort and 
nutrition to the patient while efforts are directed 
at identifying and correcting the underlying 
disease so that more specific treatment can be 
provided. • Symptomatic therapy includes 
correcting fluid deficits and electrolyte derange-  
ments, control of pain and/or nausea, reduction 
in environmental stressors, and modification of 
the diet to improve palatability.
ACTIVITY
N/A
DIET
• Palatability can be improved by adding 
flavored toppings such as low‐sodium broth, 
increasing the moisture, fat, or protein 
content of the food, and warming the food to 
body temperature. • When learned food 
aversion is suspected, food should be removed 
immediately at the first signs of aversion.
Depends on specific diagnosis.
N/A
• Pharmacologic interventions aimed at 
improving appetite should not replace diagnostic 
efforts to identify the specific cause(s) of 
decreased appetite. • Mirtazapine antagonizes 
inhibitory, presynaptic, α2‐adrenergic receptors, 
facilitating release of norepinephrine and 
serotonin (5‐HT). It is also a 5‐HT2 and 5‐HT3 
antagonist on the postsynaptic neuron. 
Stimulation of 5‐HT1 produces antidepressant 
effects, while inhibition of 5‐HT2 and 5‐HT3 
produces anti‐emetic and appetite‐stimulating 
effects. Canine dosing is 0.5 mg/kg q24h. 
Mirataz® is FDA approved for use in cats, with a 
recommended dose of a 1.5 in. strip applied to 
the inner pinna once daily for 14 days. 
Alternatively, 1.88 mg/cat PO q24–48h (for cats 
with chronic kidney disease) can be given to 
stimulate appetite. • Capromorelin is a ghrelin 
receptor agonist that stimulates appetite centrally 
in the hypothalamus. Entyce® is capromorelin, 
approved by the FDA for dogs as an appetite 
stimulant. A trial in healthy laboratory beagles 
demonstrated significant increases in food 
consumption and weight compared to placebo, 
and a clinical field trial in inappetent client‐
owned dogs demonstrated increases in appetite 
and body weight compared to placebo. Dosing 
at 3 mg/kg PO q24h is safe for long‐term 
administration. Capromorelin is not approved 
for cats, though a safety trial has been published 
and clinical trials are underway. • Diazepam 
(0.1 mg/kg IV q24h) is a short‐acting appetite 
stimulant with sedative properties. Oral diazepam should be avoided in cats due to 
possible idiosyncratic hepatotoxicosis. 
• Cyproheptadine (0.2–0.4 mg/kg PO, 10–20 
minutes prior to feeding), an antihistamine with 
antiserotonergic properties, has been used as an 
appetite stimulant with mixed success. 
• Prokinetics such as metoclopramide (0.2–
0.4 mg/kg SC/PO q8–12h), ranitidine (2 mg/kg 
SC/IV/PO q12h), or erythromycin (0.5–1 mg/
kg PO q8–12h) are useful if anorexia is associated  
with ileus. • Antiemetics are useful in decreasing 
nausea or vomiting, but are not appetite 
stimulants. Ondansetron (0.5–1.0 mg/kg SC/
IV/PO q12h) and dolasetron (0.6–1.0 mg/kg 
SC/IV/PO q24h) are potent antiemetics as 5‐
HT3 antagonists. Maropitant is a substance P 
analogue, which binds neurokinin‐1 receptors in 
the chemoreceptor trigger zone (CRTZ) and 
vomiting center, inhibiting vomiting. Cerenia ® is 
maropitant, approved by the FDA for dogs and 
cats as an antiemetic (dogs: 1 mg/kg SC/IV or 
2 mg/kg PO q24h; cats: 1 mg/kg SC/IV/PO 
q24h). • Omega‐3 fatty acids can reduce 
inflammatory cytokines and have modest benefit 
for appetite.
Avoid antiemetics and prokinetics if GI 
obstruction is present or suspected.
N/A
Mirtazapine should not be combined with 
drugs that interact with or affect serotoninergic 
systems including monoamine oxidase 
inhibitors (MAOIs), tricyclic antidepressants 
(TCAs), and selective serotonin reuptake 
inhibitors (SSRIs). Ondansetron and dolasetron, 
as well as metoclopramide, are 5‐HT3 
antagonists, and care should be used with 
combining these drugs with mirtazapine.
N/A
  FOLLOW‐UP
• Body weight, body and muscle condition 
score, and hydration assessment. • Monitor 
caloric intake to ensure return of appetite is 
sufficient to meet nutritional needs.
N/A
• Dehydration, malnutrition, cachexia, and 
sarcopenia are sequelae of prolonged anorexia/
hyporexia/dysrexia; these exacerbate the 
underlying disease. • A loss of more than 
25–30% of body protein compromises the 
immune system and muscle strength, and death 
results from infection and/or cardiopulmonary 
failure. • Hepatic lipidosis is a possible 
complication of anorexia, particularly in cats. • Breakdown of the intestinal mucosal barrier 
further compromises debilitated patients.
Depends on the underlying cause(s).
N/A
Nutritional support and glucose‐containing 
fluids may be necessary to treat or prevent 
hypoglycemia in anorectic puppies and kittens.
N/A
N/A
SYNONYMS
N/A
SEE ALSO
Weight Loss and Cachexia.
• 5‐HT = 5‐hydroxytryptamine (serotonin). 
• GI = gastrointestinal. • MAOI = monoamine 
oxidase inhibitor. • PYY = peptide tyrosine 
tyrosine. • RER = resting energy requirement. 
• SSRI = selective serotonin reuptake inhibitor. 
https://entyce.aratana.com/resources/clinical‐ 
references
Forman MA. Anorexia. In: Ettinger SJ, Feldman 
EC, Côté E, eds. Textbook of Veterinary 
Elsevier Saunders, 2017, pp. 97–100.
Quimby JM, Lunn KF . Mirtazapine as an 
appetite stimulant and anti‐emetic in cats 
with chronic kidney disease: a masked 
placebo‐controlled crossover clinical trial. 
Vet J 2013, 197(3):651–655.
Schermerhorn T. Gastrointestinal endocrinol-
ogy. In: Ettinger SJ, Feldman EC, Côté E, 
eds., Textbook of Veterinary Internal 
Medicine, 8th ed. St. Louis, MO: Elsevier 
Saunders, 2017, pp. 1833–1838.
Wofford JA, Zollers B, Rhodes L, et al. 
Evaluation of the safety of daily administra-
tion of capromorelin in cats. J Vet 
Pharmacol Ther 2018, 41(2):324–333.
Author  Andrea Wang Munk
Kathryn E. Michel.
available online(continued)  Anorexia

96 Blackwell’s Five-Minute Veterinary Consult  
AAntebrachial Growth Deformities
  BASICS
Abnormally shaped antebrachium and distal 
part of the thoracic limb, and/or malalign-
ments of the elbow or antebrachiocarpal 
joints that result from maldevelopment of the 
radius or ulna in the growing animal.
• Antebrachium—predisposed to deformities 
resulting from growth of one bone after 
premature growth cessation or growth 
retardation of the paired bone.
• Decreased rate of elongation in one bone 
behaves as a retarding strap; the growing 
paired bone must twist and curve around the 
short bone or overgrow at the elbow or 
carpus; causes joint malalignment.
• Normal growth—bones elongate through the 
process of endochondral ossification, which 
occurs in the physis; physis closure occurs when 
the germinal cell layer stops producing new 
cartilage and the existing cartilage hypertro -
phies, ossifies, and is remodeled into bone.
• Hereditary—may be a component of 
common elbow joint malalignment in many 
chondrodysplastic breeds (e.g., basset hound 
and Lhasa apso).
• Osteochondrosis (OC) or dietary oversupple -
mentation—possibly associated with retarda -
tion of endochondral ossification (retained 
cartilaginous cores) in giant-breed dogs.
• Hypertrophic osteodystrophy (HOD)—  
juvenile growth syndrome with physeal and 
periosteal inflammation that may impede growth.
• T rauma—most common cause; if germinal 
cell layer of the physis is damaged, new 
cartilage production and bone elongation are 
stopped. Commonly occurs with injury 
(fractures or crushing injuries) involving the 
distal ulnar or radial growth plates.
GENETICS
• Skye terriers—reported as a recessive 
inheritable trait.
• Chondrodysplastic breeds (dogs)—  
disturbed endochondral ossification results in 
asynchronous growth of the paired bone 
system, resulting in altered growth, angular 
deformity, and possible elbow malalignment.
• T raumatic—may occur in up to 10% of 
actively growing dogs that sustain injuries of 
the antebrachium; uncommon in cats.
• Elbow malalignment syndrome ± angular 
deformity (chondrodysplastic dog breeds)—
fairly common and can be bilateral; clinical 
abnormality in affected individuals is variable.
• Nutritionally induced—incidence decreasing 
as nutritional standards are improved.• Congenital agenesis of the radius (cats and 
rarely dogs)—occurs infrequently; results in 
severely bowed antebrachium and carpal 
subluxation.
Species
• Skye terrier—recessive inheritable form.
• Chondrodysplastic and toy breeds (especially 
basset hound, dachshund, Lhasa apso, Pekingese, 
Jack Russell terrier)—may be predisposed to 
elbow malalignment and incongruity.
• Giant breeds (e.g., Great Dane, wolfhound)—  
may be induced by rapid growth owing to 
excessive or unbalanced nutrition, OC, or HOD.
• T raumatic—any time during the active 
growth phase.
• Elbow malarticulations—during growth; 
may not be recognized until secondary 
arthritic changes become severe, occasionally 
at several years of age.
N/A
SIGNS
• Longer-limbed dogs—angular deformities 
generally more common.
• Shorter-limbed dogs—tend to develop 
more severe joint malalignments.
• Age at time of premature closure—affects 
relative degree of deformity and joint malarticula -
tion; dogs with more growth potential remaining 
tend to develop more severe deformity.
• T raumatic—progressive limb angulation or 
lameness noticed 3–4 weeks after injury; 
owner may not be aware of causative event.
• Developmental elbow malalignments—
insidious onset of lameness in one or both 
thoracic limbs; most apparent after exercise.
Premature Distal Ulnar Closure
• Results in three deformities of the distal 
radius—lateral deviation (valgus), cranial 
bowing (procurvatum), and external torsion 
resulting in supination of the manus.
• Relative shortening of limb length—if 
unilateral can compare to the contralateral 
normal limb.
• Caudolateral subluxation of the radiocarpal 
joint and malarticulation of the elbow joint— 
may occur; causes lameness and painful joint 
restriction.
Premature Radial Physeal Closure
• Affected limb—significantly shorter than 
the normal contralateral limb.
• Severity of lameness—depends on degree of 
joint malarticulation.• Complete symmetric closure of distal physis—
may note straight limb with a widened radiocarpal 
or radiohumeral joint space; may note caudal 
bow (recurvatum) to radius and ulna.
• Asymmetric closure of medial aspect of 
distal radial physis—varus angular deformity; 
occasionally internal torsion and pronation.
• Closure of lateral aspect of distal radial 
physis—valgus angular deformity; external 
torsion and supination.
• Closure of proximal radial physis with 
continued ulnar growth—malarticulation of the 
elbow joint; widened radiohumeral space; and 
proximal subluxation of the humeroulnar joint 
(increased humerus to anconeal process space).
CAUSES
• T rauma.
• Developmental basis.
• Nutritional basis.
• Thoracic limb trauma.
• Excessive dietary supplementation.
  DIAGNOSIS
• Elbow dysplasia.
• Fragmented medial coronoid process (FMCP).
• Ununited anconeal process (UAP).
• Panosteitis.
• Flexor tendon contracture.
• HOD.
N/A
N/A
IMAGING
• Damage to growth potential of the 
physis—commonly cannot be seen at the 
time of trauma; usually 2–4 weeks before 
radiographically apparent.
• Craniocaudal and mediolateral radiographic 
views—include both entire elbow and carpal 
joints; compare with normal contralateral limb.
• Degree of angular deformities and relative 
shortening—determined by comparing relative 
lengths of radius and ulna within the deformed 
pair to the normal contralateral pair.
• Degree of torsional deformity—cross-
sectional imaging and creation of models 
using stereolithography is most useful for full 
appreciation of torsional deformity.
• Elbow and carpal joints—evaluate for malalign-  
ment and degenerative change; presence of 
degenerative change is associated with less 
optimal outcome following surgical treatment.
• Elbow joint—evaluate for associated UAP 
and FMCP .
N/A

Canine and Feline, Seventh Edition  97
A
Cartilage of abnormal growth plate often 
replaced with bone. Angular deformity can 
occur due to retained cartilage core (OC) of 
the distal ulnar physis.
  TREATMENT
• Genetic predisposition—do not breed.
• T raumatic physeal damage—not seen at 
time of injury; revealed 2–4 weeks later.
• In young ( <6 months) animals, surgical 
treatment is generally recommended as soon 
as possible following diagnosis; treatment 
may require multiple surgical procedures.
N/A
ACTIVITY
Exercise restriction—reduces joint malalign-
ment damage; slows arthritic progression.
DIET
• Decrease nutritional supplementation in 
giant-breed dogs—slows rapid growth; may 
reduce incidence.
• Avoid excess weight—helps control arthritic 
pain resulting from joint malalignment and 
overuse.
• Discuss heritability in chondrodysplastic 
breeds.
• Explain that damage to physeal growth 
potential is not apparent at time of trauma 
and that the diagnosis is often made 2–4 
weeks following an injury.
• Discuss the importance of joint malalign-
ment and resultant osteoarthritis as primary 
causes of lameness.
• Emphasize that early surgical treatment 
leads to a better prognosis.
• Depending on the patient’s age, treatment 
may involve multiple procedures.
• Premature closure of the distal ulnar physis in 
a patient <5–6 months of age (significant 
amount of radial growth potential remaining)—
treated with partial ulnar ostectomy; valgus 
deformities ≤25° may improve and may not 
require additional surgery; young patients and 
those with more severe deformities often require 
a second definitive correction after maturity.
• Radial or ulnar physeal closure in a mature 
patient (limited or no growth potential) 
requires definitive deformity correction, joint 
realignment, or both.• Deformity (torsional and angular) correction—  
may be accomplished with a variety of osteotomy 
techniques; may be stabilized with several 
different internal or external fixation devices.
• Joint malalignment (particularly elbow)—
must correct to minimize arthritis develop-
ment (primary cause of lameness); typically 
performed via dynamic proximal ulnar 
osteotomy (use triceps brachii muscle traction 
and joint pressure) or shortening longer bone 
(radial or ulnar ostectomy).
• Significant limb length discrepancies—dis-
traction osteogenesis; osteotomy of the 
shortened bone is progressively distracted at 
the rate of 1 mm/day with an external fixator 
system to create new bone length.
Anti-inflammatory drugs—symptomatic 
treatment of osteoarthritis.
Corticosteroids—do not use owing to 
potential systemic side effects and cartilage 
damage seen with long-term use.
Nonsteroidal anti-inflammatory drugs 
(NSAIDs)—gastrointestinal irritation or 
renal/hepatic toxicity may preclude use in 
some patients.
N/A
N/A
  FOLLOW-UP
• Postoperative—depends on surgical treatment.
• Periodic checkups—evaluate arthritic status 
and anti-inflammatory therapy.
• Selective breeding of susceptible breeds.
• Avoid dietary oversupplementation in 
rapidly growing giant-breed dogs.
Routinely seen with various osteotomy 
fixation techniques (e.g., infection, nonunion 
of osteotomy, fixator pin tract inflammation, 
undercorrection).EXPECTED COURSE AND PROGNOSIS
• Best results seen with early diagnosis and 
surgical treatment—minimizes osteoarthritis.
• Premature ulnar closure—easier to manage 
than premature closure of the radial growth 
plates; prognosis dependent on severity of the 
deformity, joint congruity, and presence of 
degenerative joint disease; prognosis worsens 
with increasing severity.
• Limb lengthening by distraction osteogenesis—  
requires extensive postoperative management 
by the veterinarian and owner; high rate of 
• OC.
• HOD.
• U A P.
The younger the patient at the time of 
traumatically induced physeal closure, the 
more severe the deformity and 
malarticulation.
N/A
N/A
SYNONYMS
Radius curvus.
• FMCP = fragmented medial coronoid 
process.
• HOD = hypertrophic osteodystrophy.
drug.
• OC = osteochondrosis.
• UAP = ununited anconeal process.
Fox DB. Radius and ulna. In Johnston SA, 
Tobias KM, eds. Veterinary Surgery Small 
Animal, 2nd ed. St. Louis, MO: Elsevier 
Saunders, 2018, pp. 896–920.
Fox DB, Tomlinson JL. Principles of angular 
limb deformity correction. In Johnston SA, 
Saunders, 2018, pp. 762–774.
Author  Spencer A. Johnston
Consulting Editor  Mathieu M. Glassman
available online(continued)  Antebrachial Growth Deformities

98 Blackwell’s Five-Minute Veterinary Consult  
AAnterior Uveitis—Cats
  BASICS
• Inflammation of the anterior uveal tissues, 
including iris (iritis), ciliary body (cyclitis), 
or both (iridocyclitis). •  May be associated 
with concurrent posterior uveal and retinal 
inflammation (choroiditis; chorioretinitis). 
• Unilateral or bilateral.
• Increased permeability of the blood–
aqueous barrier due to infectious, immune-
mediated, neoplastic, traumatic, or other 
causes; plasma proteins and blood cells enter 
aqueous humor. •  Disruption of blood–
aqueous barrier initiated and maintained by 
chemical mediators.
• Ophthalmic. •  Other systems if underlying 
disease.
• Relatively common. •  T rue incidence/
prevalence unknown.
Geographic location may affect incidence of 
certain infections.
Species
Cat
• Mean age 7–9 years. •  Any age may be 
affected.
Males more commonly affected than females.
SIGNS
• Cloudy eye—corneal edema, aqueous flare, 
hypopyon. •  Painful eye—blepharospasm, 
photophobia, or rubbing eye; usually less 
severe than dogs. •  Red eye—conjunctival 
hyperemia and ciliary flush; usually less severe 
than dogs. •  Vision loss—variable.
A thorough physical examination is crucial.
Ophthalmic Findings
• Ocular discomfort—manifest by blepharo -
spasm and photophobia. •  Ocular 
discharge—usually serous; sometimes mucoid 
to mucopurulent. •  Conjunctival hyperemia—  
bulbar and palpebral conjunctiva affected. 
• Corneal edema—diffuse; mild to severe. 
• Keratic precipitates—multifocal aggregates 
of inflammatory cells adherent to corneal 
endothelium; most notable ventrally. 
• Aqueous flare—cloudiness of aqueous 
humor due to increased protein content and 
cellular debris; visualized with a bright, 
narrow beam of light shone through anterior chamber. •  Ciliary flush—injection of deep 
perilimbal anterior ciliary vessels. •  Deep 
corneal vascularization—circumcorneal 
distribution (brush border). •  Miosis or 
resistance to pharmacologic dilation. •  Iridal 
swelling—may be generalized or nodular. 
• Reduced intraocular pressure (IOP) 
consistent with anterior uveitis, but not 
uniform finding. •  Posterior synechia—
adhesions between posterior iris and anterior 
lens surface. •  Fibrin in anterior chamber. 
• Hypopyon or hyphema—accumulations of 
white or red blood cells, respectively, in 
anterior chamber; usually settle in ventral 
aspect of chamber, but may be diffuse. 
• Chronic changes may include rubeosis iridis, 
iridal hyperpigmentation, secondary cataract, 
lens luxation, pupillary seclusion, iris bombé, 
secondary glaucoma, and phthisis bulbi.
CAUSES
• Infectious—mycotic ( Blastomyces  spp., 
Cryptococcus neoformans , Coccidiodes immitis , 
Histoplasma capsulatum ); protozoal 
(Toxoplasma gondii , Leishmania infantum ); 
bacterial ( Bartonella  spp., Mycobacterium  
spp., or other bacteria); viral (feline immuno-  
deficiency virus [FIV], feline leukemia virus 
[FeLV], feline coronavirus [FCoV], feline 
herpesvirus type 1 [FHV-1]); parasitic 
(ophthalmomyiasis, ocular nematodiasis). 
• Idiopathic—lymphocytic-plasmacytic 
uveitis. •  Immune-mediated—reaction to 
lens proteins (due to cataract or lens trauma/
rupture). •  Neoplastic—primary ocular 
tumors, metastasis to uveal tract. •  Metabolic—  
hyperlipidemia, hyperviscosity, systemic 
hypertension. •  Miscellaneous—trauma 
(blunt or penetrating), ulcerative keratitis, 
corneal stromal abscess, toxemia.
Immune suppression and geographic location 
may increase risk for certain infectious causes 
of uveitis.
  DIAGNOSIS
• Conjunctivitis—redness limited to 
conjunctival hyperemia (no ciliary flush); 
discharge thicker and more copious than 
uveitis; discomfort alleviated by topical 
anesthetic. •  Glaucoma—elevated IOP , 
dilated pupil, Haab’s striae, and buphthalmos. 
• Ulcerative keratitis—corneal fluorescein 
staining detects ulcers; corneal edema is either 
localized to or most severe at site of ulcer; 
ocular discharge thicker and more copious 
than uveitis; discomfort alleviated by topical 
anesthetic. •  Horner’s syndrome—miosis, 
enophthalmos, and nictitans protrusion are 
similar, but Horner’s is nonpainful without 
ocular discharge; ptosis with Horner’s is not blepharospasm, as the latter is an active 
process; minor conjunctival hyperemia may 
be noted with Horner’s, but cornea and 
anterior chamber are clear; clinical signs 
resolve with topical ophthalmic 1–10% 
phenylephrine.
• CBC—normal, or reflects underlying disease. 
• Biochemistry—most common abnormality 
is elevated serum proteins (usually due to 
polyclonal gammopathy). •  Urinalysis—
normal, or reflects underlying disease.
• Serum titers for FeLV, FIV, and FCoV; 
FCoV titers not specific for feline infectious 
peritonitis (FIP), but very high titers may 
increase the index of suspicion; reverse 
transcription polymerase chain reaction 
(RT-PCR) testing can help support diagnosis, 
but not definitive. •  Toxoplasma gondii  serum 
immunoglobulin (Ig) M and IgG titers and/
or PCR performed on serum and/or aqueous 
humor. •  Bartonella  spp. serology, PCR 
(serum or aqueous humor).
IMAGING
• Thoracic radiography—may show evidence 
of metastatic or infectious disease. •  Ocular 
ultrasound—if opacity of ocular media 
precludes direct examination; may reveal 
intraocular neoplasm or retinal detachment.
• Tonometry—low IOP consistent with 
uveitis; elevated IOP indicates glaucoma 
(primary or secondary to uveitis). •  Ocular 
centesis—if retinal detachment is present, 
cytology of subretinal aspirate may reveal 
causative agents; anterior chamber centesis for 
cytology, titers, or FCoV 
immunocytochemistry.
• Lymphoplasmacytic infiltrate of iris and 
ciliary body (either diffuse or nodular) is most 
common histopathologic finding. 
• Histopathologic—may observe corneal 
edema, peripheral corneal deep stromal 
vascularization, keratic precipitates, preiridal 
fibrovascular membrane, anterior or posterior 
synechia, entropion or ectropion uveae. 
Leukocyte accumulation in iris, ciliary body, 
sclera, choroid (lymphocytic, plasmacytic, 
suppurative, or granulomatous infiltrates, 
depending on etiology), secondary cataract, 
cyclitic membrane, vitreal traction bands, and 
retinal detachment.
  TREATMENT
Outpatient

Canine and Feline, Seventh Edition  99
A
ACTIVITY
No changes.
DIET
• Systemic disease may cause ophthalmic signs; 
emphasize importance of appropriate diagnostic 
testing. •  In addition to symptomatic treatment, 
treatment of underlying disease (when possible) 
is paramount. •  Inform of potential 
complications and emphasize compliance with 
treatment and follow-up recommendations to 
reduce likelihood of complications.
• None in most cases. •  Specific instances 
include removal of ruptured lenses and 
surgical management of secondary glaucoma. 
• Chronic uveitis leading to secondary 
glaucoma commonly requires enucleation of 
the eye. •  Enucleation is recommended in 
cats with uveitis related to diffuse iris 
melanoma or other intraocular tumors.
Corticosteroids
T opical
• Prednisolone acetate 1% or dexamethasone 
0.1%—apply 2–8 times daily, depending on 
severity of disease; taper as condition resolves. 
• Stopping topical corticosteroids abruptly 
may result in rebound ocular inflammation.
Subconjunctival
• Often not required; indicated only in severe 
cases as one-time injection. •  T riamcinolone 
acetonide—4 mg by subconjunctival injection. 
• Methylprednisolone—4 mg by 
subconjunctival injection.
Systemic
• Prednisone—1–3 mg/kg/day PO initially; 
taper dose after 7–10 days. •  Only if 
infectious causes of uveitis have been ruled 
out.
Nonsteroidal Anti-inflammatory Drugs 
(NSAIDs)
T opical
• Flurbiprofen—apply 2–4 times daily, 
depending on severity of disease. 
• Diclofenac or ketorolac—apply 2–4 
times daily, depending on severity of  
disease.
Systemic
• Meloxicam—0.3 mg/kg SC once. 
• Robenacoxib—1 mg/kg PO once daily; 
limit duration of use to 3 days.Topical Mydriatic/Cycloplegic
Atropine sulfate 1%—apply 1–4 times daily, 
depending on severity of disease. Use lowest 
frequency adequate to maintain dilated pupil; 
taper medication as condition resolves. 
Ointment in cats causes less salivation.
• Avoid the use of miotic medications, 
including topical prostaglandins (e.g., 
latanoprost), in the presence of uveitis. 
• Topical and subconjunctival corticosteroids 
are contraindicated with ulcerative keratitis. 
• Corticosteroids (especially systemic) 
should be avoided in cats with systemic 
hypertension. •  Avoid systemic nonsteroidal 
anti-inflammatory drugs (NSAIDs) in cats 
with renal disease and in combination with 
corticosteroids.
Owing to concern for secondary glaucoma, 
topical atropine should be used judiciously 
and IOP monitored periodically.
Systemic corticosteroids and NSAIDs should 
not be used concurrently.
  FOLLOW-UP
Recheck in 3–7 days, depending on severity 
of disease. IOP should be monitored to detect 
secondary glaucoma. Frequency of subse-
quent rechecks dictated by severity of disease 
and response to treatment.
• Secondary glaucoma—common 
complication of chronic uveitis in cats. 
• Secondary cataract. •  Lens luxation. 
• Retinal detachment. •  Phthisis bulbi.
• Guarded prognosis for affected eyes; 
depends on underlying disease and response 
to treatment. •  Cats with treatable underlying 
disease (e.g., toxoplasmosis) are more likely to 
have a favorable ophthalmic outcome than 
those with idiopathic lymphoplasmacytic 
uveitis or untreatable underlying condition 
(e.g., FIP , FIV).
• Younger cats more likely to be diagnosed 
with infectious uveitis. •  Older cats at higher risk of idiopathic lymphocytic-plasmacytic 
uveitis and intraocular neoplasia.
• None in most cases. •  Some systemic 
infections causing uveitis may pose a risk to 
immunocompromised owners.
Avoid systemic corticosteroids. Because of 
systemic absorption, topical corticosteroids 
may also pose a risk, especially with frequent 
application.
SYNONYMS
Iridocyclitis
SEE ALSO
• Red Eye.
• FCoV = Feline coronavirus.
• FHV-1 = feline herpesvirus type 1.
• FIP = feline infectious peritonitis.
• IOP = intraocular pressure.
drug.
• RT-PCR = reverse transcription polymerase 
chain reaction.
Cullen C, Webb A. Ocular manifestations of 
systemic diseases. Part 2: The cat. In: Gelatt 
KN, ed., Veterinary Ophthalmology, 5th 
ed. Ames, IA: Wiley-Blackwell, 2013, 
pp. 1978–2036.
Miller P . Diseases of the uvea. In: Maggs DJ, 
Miller PE, Ofri R, eds., Slatter’s 
Fundamentals of Veterinary Ophthalmology, 
6th ed. St. Louis, MO: Elsevier Saunders, 
2018, pp. 254–276.
Pickett JP . Anterior uvea and anterior 
chamber. In: Martin C, Pickett J, Spiess B, 
eds., Ophthalmic Disease in Veterinary 
Medicine. Boca Raton, FL: CRC Press, 
2018, pp. 411–474.
Stiles J. Feline ophthalmology. In: Gelatt KN, 
ed., Veterinary Ophthalmology, 5th ed. 
Ames, IA: Wiley-Blackwell, 2013, pp. 
1477–1559.
Author  Ian P . Herring
available online(continued)  Anterior Uveitis—Cats

100  Blackwell’s Five-Minute Veterinary Consult  
AAnterior Uveitis—Dogs
  BASICS
• Inflammation of anterior uvea, including 
iris (iritis), ciliary body (cyclitis), or both 
(iridocyclitis). •  May be associated with 
posterior uveal and retinal inflammation 
(choroiditis; chorioretinitis). •  Unilateral or 
bilateral.
• Increased permeability of blood–aqueous 
barrier due to infectious, immune-mediated, 
traumatic, or other causes allows plasma 
proteins and blood cells to enter aqueous 
humor. •  Disruption of blood–aqueous 
barrier is initiated and maintained by 
numerous mediators.
• Ophthalmic. •  Other systems if systemic 
disease.
Species
Dog
• None for most causes. •  Uveitis associated 
with iridociliary cysts in golden retriever 
(golden retriever pigmentary uveitis) and 
Great Dane. •  Increased incidence of 
uveodermatologic syndrome in Siberian 
husky, Akita, Samoyed, and Shetland 
sheepdog.
• Any age. •  Uveodermatologic syndrome—
mean 2.8 years. •  Golden retriever pigmentary 
uveitis—mean 8.6 years.
SIGNS
• Red eye (conjunctival hyperemia, ciliary 
flush). •  Cloudy eye (corneal edema, aqueous 
flare, hypopyon). •  Painful eye (blepharospasm, 
photophobia, or rubbing eye). •  Vision 
loss—variable.
Thorough physical examination is critical.
• Ocular discomfort—blepharospasm, 
photophobia, and rubbing eye. •  Ocular 
• Corneal edema—diffuse; mild to severe. • Keratic precipitates—aggregates of 
inflammatory cells adherent to corneal 
endothelium. •  Aqueous flare—cloudiness of 
aqueous humor due to increased protein 
content and cellular debris; best seen with a 
bright, narrow beam of light shone through 
anterior chamber. •  Ciliary flush—injection 
of deep perilimbal anterior ciliary vessels. 
• Deep corneal vascularization—circum -
corneal distribution. •  Miosis and/or 
swelling. •  Reduced intraocular pressure 
(IOP) is consistent with uveitis, but not a 
• Hypopyon or hyphema—accumulation of 
anterior chamber; usually settles horizontally 
in ventral aspect of chamber, but may be 
diffuse. •  Chronic changes may include 
rubeosis iridis, iridal hyperpigmentation, 
secondary cataract, lens luxation, pupillary 
seclusion, iris bombé, secondary glaucoma, 
and phthisis bulbi.
CAUSES
• Infectious—fungal ( Blastomyces dermatitidis , 
Cryptococcus neoformans , Coccidioides immitis , 
Histoplasma capsulatum , Candida  spp., 
Aspergillus  spp., Encephalitozoon cuniculi ), 
protozoal ( Toxoplasma gondii , Neospora 
caninum , Leishmania donovani ), rickettsial 
(Ehrlichia canis , Rickettsia rickettsii ), bacterial 
(Leptospira  spp., Bartonella  spp., Brucella canis , 
Borrelia burgdorferi , and others), algal 
(Prototheca  spp.), viral (adenovirus, distemper, 
rabies, herpes), parasitic (ocular filariasis, 
ocular nematodiasis, ophthalmomyiasis). 
• Immune-mediated—reaction to lens 
proteins (due to cataract or lens trauma), 
uveodermatologic syndrome, postvaccinal 
reaction to canine adenovirus vaccine, 
vasculitis. •  Neoplastic—primary ocular 
tumors (uveal melanoma, iridociliary adenoma/  
adenocarcinoma), metastasis to uveal tract 
(e.g., lymphosarcoma). •  Metabolic—
hypertension. •  Miscellaneous—idiopathic, 
trauma, golden retriever pigmentary uveitis, 
ulcerative keratitis, corneal stromal abscess, 
scleritis, lens instability/luxation.
may increase risk for infectious causes of 
uveitis; consider breed predispositions.
  DIAGNOSIS
conjunctival hyperemia (i.e., no ciliary flush); discharge usually thicker and more 
copious; discomfort alleviated with topical 
diffuse corneal edema, dilated pupil, Haab’s 
striae, buphthalmos. •  Lens luxation—  
corneal edema may be localized to site of 
lens contact with endothelium or diffuse as 
a result of secondary uveitis and/or 
glaucoma; breed associated. •  Ulcerative 
keratitis—corneal fluorescein stain detects 
ulcers; corneal edema localized to, or most 
severe at, site of ulcer; discomfort alleviated 
by topical anesthetic. •  Corneal endothelial 
dystrophy or degeneration—diffuse corneal 
edema with normal IOP; conjunctival 
hyperemia and ocular discomfort generally 
absent. •  Horner’s syndrome—miosis, 
enophthalmos, and nictitans protrusion in 
both conditions, but Horner’s is nonpainful 
without ocular discharge; ptosis with Horner’s 
is distinguished from blepharospasm as the 
latter is an active process; minor conjunctival 
hyperemia may be noted, but cornea and 
anterior chamber are clear; clinical signs of 
Horner’s syndrome resolve with topical 
ophthalmic 1–10% phenylephrine.
Normal, or reflect underlying disease.
Serology for infectious diseases may be 
indicated, especially in patients with signs of 
systemic illness.
IMAGING
• Thoracic radiography and abdominal 
ultrasound may be warranted for systemic 
disease. •  Ocular ultrasound is indicated if 
ocular media opacity precludes direct 
examination.
(primary disease or secondary to uveitis). 
• Ocular centesis—if retinal detachment is 
present, cytology of subretinal aspirate may 
reveal causative agents; anterior chamber 
centesis unrewarding, except in cases of 
lymphoma.
Histopathologic—may observe corneal 
fibrovascular membrane, anterior or 
posterior synechia, entropion or ectropion 
uveae. Leukocyte accumulation in iris, 
ciliary body, sclera, choroid may be 
lymphocytic, plasmacytic, suppurative, or 
granulomatous, depending on etiology. 
Secondary cataract, cyclitic membrane, 
vitreal traction bands, and retinal detach -
ment may be present.

Canine and Feline, Seventh Edition  101
A
  TREATMENT
ACTIVITY
• No changes in most cases. •  Reduced 
exposure to bright light may alleviate 
discomfort.
DIET
• Systemic disease may cause ophthalmic 
signs; emphasize importance of appropriate 
diagnostic testing. •  In addition to sympto -
matic uveitis treatment, treatment of 
underlying disease (when possible) is 
paramount. •  Inform of potential complications 
and emphasize compliance with treatment 
and follow-up recommendations to reduce 
likelihood of complications.
• None (most cases). •  Specific instances 
include removal of ruptured lenses, removal 
of cataracts causing uveitis (if prognosis is 
otherwise favorable), surgical management of 
corneal disease causing uveitis, and surgical 
management of secondary glaucoma.
Topical
acetonide—4–6 mg, subconjunctival injection. 
• Methylprednisolone—3–10 mg, 
Systemic
• Prednisone—0.5–2.2 mg/kg/day PO 
initially; taper dose after 7–10 days. Long-term 
treatment with immunosuppressive medication 
may be warranted for immune-mediated uveitis. 
• Use only if systemic infectious causes of 
uveitis have been ruled out.Nonsteroidal Anti-inflammatory Drugs 
(NSAIDs)
Topical
• Less effective than topical corticosteroids; 
can be combined with topical steroids. 
• Flurbiprofen, diclofenac, ketorolac—apply 
2–4 times daily, depending on severity of 
disease.
Systemic
• Do not use concurrently with systemic 
corticosteroids; avoid in presence of hyphema. 
• Carprofen—2.2 mg/kg PO q12h or 
4.4 mg/kg PO q24h. •  Meloxicam— 
0.2 mg/kg on day 1, followed by 0.1 mg/kg 
PO q24h. •  Deracoxib—1–2 mg/kg PO 
q24h. •  Firocoxib—5 mg/kg PO q24h.
Topical Mydriatic/Cycloplegic
depending on severity of disease; use lowest 
frequency adequate to maintain dilated pupil 
and ocular comfort; taper medication as 
condition resolves.
• Avoid topical miotic medications (e.g., 
pilocarpine), including topical prostaglandins 
(e.g., latanoprost), in presence of uveitis. 
• Avoid topical atropine in cases of uveitis 
with secondary glaucoma. •  Topical and 
subconjunctival corticosteroids are contra -
indicated with ulcerative keratitis. •  Avoid 
systemic corticosteroids in dogs with systemic 
Out of concern for secondary glaucoma, 
and IOP should be monitored periodically.
N/A
  FOLLOW-UP
secondary glaucoma. Frequency of subsequent 
rechecks dictated by severity of disease and 
response to treatment.
• Many systemic complications, including 
death, may occur due to systemic etiology of 
uveitis. •  Ophthalmic complications include secondary cataract, secondary glaucoma, lens 
luxation, retinal detachment, phthisis bulbi.
Extremely variable; depends on underlying 
disease and response to treatment.
None in most cases. Some etiologies of 
systemic infection may pose a risk to 
immune-compromised owners.
possibility of systemic absorption, topical 
corticosteroids may also pose risk, especially 
with frequent application in small dogs.
SYNONYMS
SEE ALSO
Red Eye.
drug.
systemic diseases. Part 1: The dog. In: 
Gelatt KN, ed., Veterinary Ophthalmology, 
5th ed. Ames, IA: Wiley-Blackwell, 2013, 
pp. 1897–1977.
Hendrix D. Diseases and surgery of the 
canine anterior uvea. In: Gelatt KN, ed., 
Veterinary Ophthalmology, 5th ed. 
Ames, IA: Wiley-Blackwell, 2013, 
pp. 1146–1198.
available online(continued)  Anterior Uveitis—Dogs

102  Blackwell’s Five-Minute Veterinary Consult  
AAntidepressant Toxicosis—SSRIs and SNRIs
  BASICS
• Toxicity secondary to the overdose of a 
selective serotonin reuptake inhibitor (SSRI), 
serotonin and norepinephrine reuptake 
inhibitor (SNRI), or coingestion of two types 
of serotonergic drugs.
• SSRIs include citalopram (Celexa®), 
escitalopram (Lexapro®), fluoxetine (Prozac®), 
fluvoxamine (Luvox®), paroxetine (Paxil®), 
sertraline (Zoloft®), vilazodone (Viibryd®), 
and vortioxetine (Brintellix®). SNRIs include 
desvenlafaxine (Pristiq®), duloxetine (Cymbalta®), 
levomilnacipran (Fetzima®), milnacipran 
(Ixel®, Savella®), tofenacin (Elamol®, 
Tofacine®), and venlafaxine (Effexor®).
• SSRIs and SNRIs are antidepressants 
that inhibit reuptake of serotonin, a neuro­
transmitter involved in aggression, anxiety, 
appetite, depression, migraine, pain, and sleep. 
Antidepressant effects are secondary to 
inhibition of reuptake of serotonin into 
serotonergic neurons via binding to the 
serotonin transporter, resulting in increased 
synaptic availability of serotonin. SNRIs also 
inhibit the reuptake of norepinephrine by the 
same mechanism.
• Excessive stimulation of serotonin receptors 
can occur by enhanced serotonin synthesis, 
increased presynaptic serotonin release, 
inhibition of serotonin uptake into the 
presynaptic neuron, inhibition of serotonin 
metabolism, or serotonin agonism. Ingesting 
too much of one medication or a combination 
of medications that increase serotonin via 
different methods can lead to serotonin 
syndrome.
• Serotonin syndrome is characterized in 
humans as a combination of symptoms that 
include at least three of the following: 
myoclonus, mental aberration, agitation, 
hyperreflexia, tremors, diarrhea, ataxia, or 
hyperthermia.
• Toxic dosage varies widely among 
commonly available SSRIs and SNRIs 
and is not well defined in veterinary medicine.
• Cardiovascular—decreased vascular tone 
(hypotension), increased heart rate and stroke 
volume (tachycardia).
• Gastrointestinal—increased smooth muscle 
contractility (vomiting, diarrhea).
• Nervous—stimulation (agitation, restlessness, 
seizures) and altered mental status (vocalization, 
disorientation).
• Neuromuscular—autonomic dysfunction 
(hyperactivity) and neuromuscular 
hyperactivity (hyperreflexia, myoclonus, 
tremors).• Ophthalmic—increased autonomic 
function (mydriasis).
• Respiratory—increased bronchial smooth 
muscle contraction (dyspnea).
Second most common human prescription 
medication toxicosis (after cardiac medicat ­ 
ions).
Species
Dogs and cats.
Any age can be affected.
SIGNS
• Agitation or lethargy.
• Dilated pupils.
• T remors.
• Hypersalivation.
• Diarrhea.
• Seizures.
• Nystagmus.
• Agitation.
• Ataxia.
• Mydriasis.
• T remors.
• Disorientation.
• Hyperthermia.
• Vocalization.
• Hypotension.
• Blindness.
• Death.
CAUSES
• SSRI/SNRI overdose—accidental 
exposure, inappropriate administration, or 
therapeutic use.
• Ingestion of an SSRI/SNRI along with 
another class of medications that increases 
serotonin (tricyclic antidepressants [TCAs], 
monoamine oxidase inhibitors [MAOIs], 
novel antidepressants, tramadol, fentanyl, 
meperidine, amphetamines, cocaine, 
dextromethorphan, 5 ­hydroxytryptophan 
[5­HTP], buspirone, bupropion, 
triptans, LSD).
• Animals on a serotonergic drug.
• Underlying liver or kidney disease; cats are 
attracted to venlafaxine and will eat multiple 
capsules.  DIAGNOSIS
• Toxicologic—TCAs, MAOIs, metaldehyde, 
lead, ethylene glycol, hops, anticholinergics, 
antihistamines.
• Nontoxicologic—meningitis (e.g., rabies, 
canine distemper), neoplasia, heat stroke, 
malignant hyperthermia.
• CBC/biochemistry—no direct changes are 
expected, but creatine kinase (CK) may be 
elevated secondary to tremors.
• Urinalysis—myoglobinuria secondary to 
rhabdomyolysis may be seen.
• Blood gas—metabolic acidosis may be 
seen.
• Testing for SSRIs/SNRIs can be performed, 
but the tests are not clinically useful.
• Note: venlafaxine will give a false positive 
for phencyclidine (PCP; angel dust) on many 
urine drug screens.
There are no diagnostic tests to confirm 
serotonin syndrome.
  TREATMENT
• Emesis (if asymptomatic and recent ingestion) 
or gastric lavage (if large number of pills 
ingested).
• Activated charcoal with cathartic (if severe 
signs are expected, may need to repeat due to 
long half ­life).
IV fluids to help maintain blood pressure and 
body temperature, and to protect kidneys 
from myoglobinuria.
If animal appears blind, sight should return.
• Agitation:
 ◦Phenothiazines (acepromazine 0.025–
0.05 mg/kg IV, titrate up as needed).
 ◦Cyproheptadine (dog, 1.1 mg/kg; cat, 
2–4 mg PO q4–6h or can be given rectally 
if vomiting).
 ◦Benzodiazepines (diazepam 0.5–2 mg/kg 
IV; see Precautions).
 ◦T remors—methocarbamol (50–150 mg/kg 
IV, titrate up as needed).

Canine and Feline, Seventh Edition  103
A
• High risk of serotonin syndrome—other 
SSRIs, SNRIs, MAOIs, TCAs, amphetamines, 
5­HTP , clarithromycin, dextromethorphan, 
lithium, St. John’s wort.
• Low risk of serotonin syndrome—tramadol, 
fentanyl, amantadine, bupropion, carbamazepine, 
codeine.
Benzodiazepines (e.g., diazepam) are reported 
by some sources to exacerbate serotonin 
syndrome and their use for SSRI/SNRI 
toxicosis is not universally recommended.
• Decreased metabolism of SSRIs/SNRIs—
cimetidine, diuretics, quinidine, lithium.
• Increased levels of medications (decreased 
metabolism)—theophylline, coumadin, 
digoxin.
  FOLLOW-UP
Blood pressure, heart rate, urine color—mon­
itor hourly, then less frequently as the animal 
remains stable.PREVENTION/AVOIDANCE
• Keep medications out of the reach of 
animals.
• Follow label directions when giving 
serotonergic drugs to animals.
Renal failure secondary to myoglobinuria 
from rhabdomyolysis; disseminated intravas­
cular coagulation (DIC) secondary to 
• Prognosis is good in most cases, with 
recovery in 12–24 hours.
• Patients that present in status epilepticus or 
with severe hyperthermia have a guarded 
prognosis.
Young and elderly animals are more at risk for 
developing serious toxicosis.
SSRIs and SNRIs can cause increased litter 
mortality and possible birth defects.ABBREVIATIONS
• 5­HTP = 5 ­hydroxytryptophan.
• CK = creatine kinase.
• PCP = phencyclidine (angel dust).
• SNRI = serotonin and norepinephrine 
reuptake inhibitor.
Pugh CM, Sweeney JT, Bloch CP , et al. 
Selective serotonin reuptake inhibitor 
(SSRI) toxicosis in cats: 33 cases (2004–
2010). J Vet Emerg Crit Care 2013, 
23(5):565–570.
Thomas DE, Lee JA, Hovda LR. Retrospective 
evaluation of toxicosis from selective 
serotonin reuptake inhibitor antidepres­
sants: 313 dogs (2005–2010). J Vet Emerg 
Crit Care 2012, 22(6):674–681.
Wismer TA. Antidepressant drug overdoses in 
dogs. Vet Med 2000, 95(7):520–525.
Author  Tina Wismer
Consulting Editor  Lynn R. Hovda(continued)  Antidepressant Toxicosis—SSRIs and SNRIs

104  Blackwell’s Five-Minute Veterinary Consult  
AAntidepressant Toxicosis—Tricyclic
  BASICS
• Toxicity secondary to the acute or chronic 
ingestion of a tricyclic antidepressant (TCA).
• TCA medications include amitriptyline, 
amoxapine, clomipramine, desipramine, 
doxepin, imipramine, maprotiline (tetracyclic 
antidepressant), nortriptyline, protriptyline, 
trimipramine, and many others.
• TCAs block the reuptake of norepine­
phrine, dopamine, and serotonin at the 
neuronal membrane. They also have 
anticholinergic activity and are thought to 
have membrane ­stabilizing effects on the 
myocardium (particularly inhibiting fast 
sodium channels in the ventricular 
myocardium). They can also have slight 
alpha ­adrenergic blocking activity and 
antihistaminic effects.
• TCAs are rapidly and well absorbed across 
the digestive tract. They can decrease GI 
motility and delay gastric emptying, resulting 
in delayed drug absorption.
• Lipophilic, protein bound, and well 
distributed across all tissues.
• They are metabolized by the liver and 
undergo enterohepatic recirculation. The 
inactive metabolites are eliminated in the 
urine.
• Nervous—increased dopamine, serotonin, 
and norepinephrine levels in the CNS 
contribute to CNS signs.
• Cardiovascular—anticholinergic effects and 
inhibition of norepinephrine reuptake 
contribute to tachycardia; alpha adrenergic 
blockade, cardiac membrane stabilization, 
and decreased cardiac contractility contribute 
to hypotension and arrhythmias.
• Gastrointestinal (GI)—anticholinergic 
effects may cause ileus and delayed gastric 
emptying.
• Ophthalmic—anticholinergic effects can 
cause pupillary dilation.
• Renal/urologic—anticholinergic effects may 
cause urinary retention.
GENETICS
Species and individual differences in 
absorption, metabolism, and elimination can 
be significant.
Incidence is unknown.
Species
NoneMean Age and Range
None
SIGNS
• Signs can occur at therapeutic doses.
• Signs of toxicosis can occur within  
30–60 minutes or be delayed by several 
hours.
• Evidence of accidental consumption of the 
owner’s or another pet’s medication.
• CNS depression (lethargy, ataxia).
• Vomiting or hypersalivation.
• Panting.
• Agitation or restlessness.
• Tachypnea or dyspnea.
• T remors.
• CNS depression or stimulation.
• Ataxia.
• Hypertension.
• Pallor.
• Cyanosis.
• Arrhythmias.
• Urinary retention.
• Constipation.
CAUSES
Accidental exposure, inappropriate 
administration, or therapeutic use.
• Concurrent use of other antipsychotic 
medication.
• Preexisting cardiac disease.
  DIAGNOSIS
• Toxicity caused by other antipsychotic 
medication, stimulant substances (e.g., 
amphetamines, cocaine, methylxanthines, or 
pseudoephedrine), or substances capable of 
causing cardiac arrhythmias (e.g., quinidine, 
propranolol, albuterol, digoxin).
• Nontoxicologic differentials include hyper­
kalemia, cardiac ischemia, cardiomyopathy, and 
other diseases of cardiac conduction.
Expected to be normal.
• Blood gases—metabolic acidosis may be noted.
• Over ­the­counter (OTC) urine drug screen 
for TCAs—can be used to determine if exposure has occurred; not useful in 
determining degree of toxicity.
• Serum TCA levels—can be used to 
determine if exposure has occurred.
IMAGING
N/A
• ECG to monitor for arrhythmias.
• Blood pressure monitoring.
No specific lesions expected.
  TREATMENT
• Outpatient—not recommended for sympto ­ 
matic patients, patients with cardiac disease, 
or patients ingesting greater than a 
therapeutic dose of TCAs.
• Inpatient—asymptomatic:
 ◦Decontamination with emesis (less than 
15 minutes of exposure time), gastric lavage 
in large exposures, and activated charcoal.
 ◦Monitor at a clinic for a minimum of 6 
hours after exposure.
• Inpatient—symptomatic: stabilize the 
cardiovascular (CV) system and CNS and 
provide supportive care.
• Fluid therapy—restore hydration due to 
vomiting, regulate blood pressure when 
hypotension is noted.
• Thermoregulation as needed.
• Enema with warm water if not defecating 
within 6–12 hours.
ACTIVITY
N/A
DIET
NPO if vomiting.
• With a prescribed TCA, instruct client to 
monitor for adverse or idiosyncratic effects, 
and to stop the medication and contact the 
clinic if they occur.
• Prevent exposure to nonprescribed 
N/A
• Emesis within 15 minutes of ingestion only 
if asymptomatic ; induce emesis with either 
hydrogen peroxide (dog, 1–2 mL/kg PO),

Canine and Feline, Seventh Edition  105
A
apomorphine (dog, 0.03–0.05 mg/kg IV/IM, 
or 0.1 mg/kg SC, or 0.25 mg instilled in 
conjunctiva of eye), or dexmedetomidine 
(cat, 7  μg/kg IM or 3.5  μg/kg IV).
• Gastric lavage under anesthesia may be 
considered with large exposures.
• After emesis (or if >15 min of exposure), 
administer activated charcoal (1–2 g/kg PO) 
with a cathartic such as sorbitol (70% sorbitol 
at 3 mL/kg) or sodium sulfate (0.25 tsp/5 kg) 
if no diarrhea.
• Repeat one ­half dose of activated charcoal 
in 4–6 hours if patient is still symptomatic.
Other
• Cyproheptadine—dogs, 1.1 mg/kg q8h PO 
or rectally; cats, 2–4 mg/cat q12–24h PO or 
rectally; used for treatment of serotonin 
syndrome.
• 20% intravenous lipid emulsion—prevents 
lipophilic TCAs from reaching site of action by 
acting as sequestrant in expanded plasma lipid 
phase; 1.5 mL/kg IV bolus followed by 
0.25 mL/kg/min IV CRI for 1 hour. Can repeat 
bolus and CRI in 4–6 hours if serum is not 
lipemic and a poor response to treatment is seen.
• Sodium bicarbonate—used to maintain 
blood pH at 7.55; if not monitoring acid ­base 
status, start with 2–3 mEq/kg IV over 15–30 
minutes in a symptomatic patient.
• Diazepam—0.5–1 mg/kg IV, repeat if 
necessary; for agitation or seizures.
• Acepromazine—0.02 mg/kg IV, repeat 
if necessary; for agitation or mild hyper  ­ 
tension.
• Phenobarbital—as needed for seizure control.
• Atropine should not be used, because TCAs 
have anticholinergic effects that are exacer­
bated by atropine.
• T razodone should not be used, because it 
can result in serotonin syndrome when given 
concurrently.
• Magnesium sulfate should not be used as a 
cathartic. Ileus or reduced GI motility will 
enhance absorption of magnesium and may 
result in magnesium toxicity.
• Beta blockers (e.g., propranolol, atenolol) 
should not be used for tachycardia because of their potential to exacerbate 
hypotension.
• Do not induce emesis in a patient already 
showing clinical signs.
N/A
• TCAs increase risk of hyperthermia, 
seizures, and death with use of monoamine 
oxidase inhibitors (MAOIs).
• Sympathomimetic and anticholinergic 
medications increase the risk for arrhythmias 
or cardiac effects from TCAs.
• Levothyroxine increases the risk for 
arrhythmias when used with TCAs.
N/A
  FOLLOW-UP
• Acid­base status—monitor for acidosis and 
if implementing sodium bicarbonate therapy.
• Blood pressure—monitor until asympto  ­ 
matic.
• ECG—monitor until asymptomatic.
Keep medications out of reach of pets.
Pulmonary edema can occur secondary to 
aggressive fluid therapy.
• Due to the variable half ­lives of the 
different TCAs, signs can last 24 hours or 
longer.
• Prognosis is generally good in patients 
exhibiting mild to moderate signs.
• Prognosis is guarded in patients exhibiting 
severe signs such as seizures, arrhythmias, or 
hypotension that are poorly responsive to 
therapy.  MISCELLANEOUS
Serotonin syndrome may occur as a result of 
TCA ingestion.
None
TCAs cross the placenta and can be found in 
breast milk; the significance of this is not 
known at this time.
SEE ALSO
SNRIs.
• Poisoning (Intoxication) Therapy.
• CV = cardiovascular.
• OTC = over ­the­counter.
• http://www.aspcapro.org/poison
Gwaltney ­Brant S. Antidepressants: tricyclic 
antidepressants. In: Plumlee KH, ed., 
Clinical Veterinary Toxicology. St. Louis, 
MO: Mosby, 2004, pp. 286–288.
Gwaltney ­Brant S, Meadows I. Use of 
intravenous lipid emulsions in veterinary 
clinical toxicology. Vet Clin North Am 
Small Anim Pract 2018, 48:933–942.
Johnson LR. T ricyclic antidepressant 
toxicosis. Vet Clin North Am Small Anim 
Pract 1990, 20:393–403.
Volmer PA. Recreational drugs: tricyclic 
antidepressants. In: Peterson ME, Talcott 
PA, eds., Small Animal Toxicology, 3rd ed. 
St. Louis, MO: Elsevier Saunders, 2013, pp. 
328–330.
dogs. Vet Med 2000, 95:520–525.
Author  Cristine L. Hayes
Consulting Editor  Lynn R. Hovda(continued)  Antidepressant Toxicosis—Tricyclic

106  Blackwell’s Five-Minute Veterinary Consult  
A
  BASICS
• A narrowing of the left ventricular outflow 
tract (LVOT) that restricts blood flow leaving 
the ventricle; most commonly congenital, 
often heritable. • Lesion is most commonly 
subvalvular in dogs, but may be valvular or 
supravalvular (more often in cats). 
• Subvalvular aortic stenosis (SAS) in dogs 
is caused by fibrous tissue manifested as 
nodules, a ridge, a ring, or a tunnel‐like lesion. 
SAS may be associated with other defects, 
including mitral valve dysplasia.
• Restriction to outflow generates pressure 
overload of left ventricle (LV). • Degree of 
obstruction is related to severity of secondary 
changes. • LV pressure overload causes 
thickened LV walls, resulting in diminished 
blood supply relative to muscle demand and 
myocardial ischemia; this may result in 
arrhythmogenesis and, if severe or infarction 
occurs, mechanical dysfunction. • Restriction 
to blood flow causes high‐velocity, turbulent 
flow across valve, which may cause endothelial 
damage, lead to aortic insufficiency (AI), and 
predispose to endocarditis. • SAS may lead to 
chamber enlargement, distortion of the mitral 
valve annulus, and mitral regurgitation, with 
possible sequela of left‐sided congestive heart 
failure (CHF). • Sudden death is common 
with severe SAS and may be secondary to 
arrhythmias or infarction.
• Cardiovascular—LV pressure overload 
leading to arrhythmias, syncope, sudden death, 
heart failure, endocarditis. • Respiratory—
possible pulmonary edema with CHF . 
• Multisystemic—possible due to low cardiac 
output or endocarditis.
GENETICS
• SAS inherited in the Newfoundland, 
golden retriever, Rottweiler, bullmastiff, and 
dogue de Bordeaux. • Mutation in phosphatidy-  
linositol‐binding clathrin assembly protein 
gene (PICALM) reported in Newfoundlands; 
screening test is available. • Dominant 
inheritance patterns proposed for 
Newfoundlands with incomplete penetrance 
responsible for disease appearing to skip 
generations. • More than one gene or 
modifying genes may be involved. • Golden 
retrievers, Rottweilers, and bullmastiffs appear 
to inherit SAS in autosomal recessive pattern, 
but no associated mutation yet identified.
• SAS is one of most common congenital heart 
defects of dogs; it is reported as second most 
common, but difficulty in diagnosing mild 
disease may underestimate true prevalence. • Aortic stenosis reported as small contributor 
of feline congenital heart disease, about 6%; 
approximately 2 out of 1,000 dogs and 0.2 per 
1,000 cats evaluated at veterinary teaching 
hospitals are diagnosed with aortic stenosis, 
SAS most often in dogs and supravalvular 
aortic stenosis most often in cats.
N/A
Species
• Newfoundland, bullmastiff, golden 
retriever, Rottweiler, bouvier des Flandres, 
dogue de Bordeaux, German shepherd, and 
boxer have highest incidence of SAS and 
familial component or heritability is reported. 
• No breed predilection reported for cats.
• Clinical signs may be seen at any age. 
• Although often inherited, SAS becomes 
identifiable during first few weeks to months 
of life as subvalvular lesion progresses. • Full 
phenotype is appreciated by 1 year of age.
N/A
SIGNS
• Many dogs show no clinical signs and have 
no relevant historical findings. • Historical 
findings related to disease severity and may 
include syncope, exercise intolerance, sudden 
death, and signs due to CHF such as respira- 
tory distress and/or coughing if severe.
• Systolic left basilar ejection murmur; may 
radiate to apex, right side of thorax, include 
carotid arteries, and if very loud the cranium; 
precordial thrill may be palpable; murmur 
intensity loosely correlated to severity; as 
disease worsens during early life, some may 
have absence of or quiet murmur that 
develops to more characteristic finding by 1 
year. • Diastolic murmur may be present with 
significant AI; combination of this diastolic 
murmur with systolic ejection murmur is 
to‐and‐fro murmur. • Arrhythmias may be 
ausculted. • Pulse deficits may be appreciated, 
often associated with ventricular arrhythmias. 
• Weak pulses may be appreciated that are 
late or slow to rise with severe SAS (pulsus 
parvus et tardus). • Tachypnea, respiratory 
distress, and crackles may occur with CHF .
• Boxers have relatively small aorta compared 
to other breeds, which can be difficult to 
distinguish from mild SAS. • Bull terriers 
overrepresented for combined mitral valve 
dysplasia and SAS. • Newfoundland dogs 
overrepresented for combined patent ductus arteriosus (PDA) and SAS. • Volume 
overload of PDA can cause relative aortic 
stenosis and be difficult to distinguish from 
PDA with mild SAS.
CAUSES
• Congenital heart disease. • Secondary to 
valvular change, as with aortic valve 
endocarditis or calcification. • Component 
of complex congenital heart disease, as with 
some cases of mitral valve dysplasia.
• Familial history of SAS. • SAS predisposes to 
aortic valve endocarditis. • Aortic valve 
endocarditis predisposes to valvar aortic stenosis.
  DIAGNOSIS
• Systolic murmur must be differentiated 
from other causes of similar murmurs. 
• Innocent or physiologic murmurs 
commonly ausculted in athletic dogs, or with 
anemia, fever, stress, or excitement. 
• Pulmonic stenosis and tetralogy of Fallot 
cause similar murmur. • Weak pulses may 
also occur with conditions that reduce cardiac 
output, such as heart failure, cardiomyopathy, 
and severe pulmonic stenosis. • Other 
obstruction to flow may cause reduced pulse 
quality, such as aortic thromboembolism, or 
rarely aortic coarctation/tubular hypoplasia.
Typically within normal limits.
Genetic testing for mutation associated with 
Newfoundland SAS is breeding tool to reduce 
frequency in this breed.
IMAGING
Thoracic Radiography
• Mild disease may be radiographically silent. 
• LV hypertrophy may be subtle, as pressure 
overload causes concentric hypertrophy. • Left 
heart enlargement. • Prominent aortic root and/
or widened mediastinum. • Lung fields typically 
normal unless CHF with pulmonary venous 
distention and interstitial to alveolar infiltrates.
• Findings variably present and associated with 
disease severity. • Ridge, ring, nodule, or 
tunnel‐like narrowing below aortic valve with 
SAS. • Thickened LV free wall or interven -
tricular septum. • Aortic valve thickening and 
increased echogenicity with valvar stenosis. 
• Mitral regurgitation and thickening of valve 
leaflets possible. • Poststenotic aortic dilation. 
• Hyperechoic myocardium associated with 
ischemia. • AI with secondary LV chamber 
enlargement and volume overload if significant. 
• Left atrial enlargement may be seen with 
significant mitral valve regurgitation. • Elevated Aortic Stenosis

Canine and Feline, Seventh Edition  107
A
LVOT flow velocity ( >2.4 m/s), with 
acceleration proximal to stenosis and turbulent 
flow distal to obstruction and valve. 
• T ransvalvular pressure gradient estimated by 
LVOT flow velocity (4 × flow velocity2); 
estimated gradients of 25–49 mmHg 
considered mild, 50–79 mmHg moderate, and 
≥80 mmHg severe. • With myocardial failure, 
estimated pressure gradient may be falsely low. 
• Effective valve orifice, if calculated, is 
reduced.
• ECG may show changes consistent with LV 
hypertrophy (tall R waves, widened QRS 
complexes, left axis deviation); signs of 
myocardial ischemia (ST segment deviation or 
slurring); ventricular arrhythmias may occur 
and contribute to syncope or sudden death. 
• Holter monitoring may be used to quantify 
arrhythmia severity and therapeutic response.
• Findings vary with severity, but typically 
include LV concentric or mixed (if significant 
AI) hypertrophy. • Variable subvalvular lesion 
of dense fibrous tissue is seen. • Myocardial 
ischemia, necrosis, and replacement fibrosis 
may be evident. • Poststenotic dilation of aorta, 
associated valvular endothelial damage, and 
sometimes left atrial enlargement are reported.
  TREATMENT
Therapy limited prior to onset of 
complications and aimed at preventing 
Aimed at relieving symptoms and 
complications such as arrhythmias, 
syncope, and CHF .
ACTIVITY
Restriction warranted with severe disease; 
exertion may increase incidence of arrhyth -
mias, syncope, and therefore risk of sudden 
death.
DIET
Modest salt restriction with CHF .
• SAS considered inherited disease; affected 
animals should not be bred. • Owners should 
be counseled on risk of endocarditis and 
appropriate antibiotics for any wounds, 
infections, or surgical procedures. • Alert 
owners to risks of sudden death, CHF , and 
increased anesthetic risk.
• No surgical or interventional technique has 
been shown to extend life beyond medical 
therapy. • Balloon valvuloplasty or combined 
cutting and traditional balloon valvuloplasty may acutely reduce pressure gradient and temporarily 
alleviate some clinical signs; however, effects not 
yet shown to be beneficial beyond those achieved 
with beta blockers. • Currently, data does not 
support surgery or intervention, but this remains 
area of continued research.
• Beta adrenergic blockers advocated with 
moderate to severe SAS, particularly with 
ventricular arrhythmias, syncope, or ECG 
evidence of ischemia; may reduce myocardial 
oxygen demand, eliminate or protect against 
ventricular arrhythmias, and reduce heart 
rate; atenolol is most common (dogs, 
0.5–1.5 mg/kg PO q12h; cats, 6.25 mg/cat 
PO q12–24h). • Therapy for ventricular 
arrhythmias, CHF , atrial fibrillation, or 
endocarditis may be required.
• Beta blockers contraindicated in animals 
with bronchoconstriction such as asthmatic 
cats. • Starting beta blockers with CHF 
contraindicated and continued use in patients 
that develop CHF is controversial.
• Beta blockers negatively impact cardiac 
output and starting low doses with gradual up‐
titration warranted. • Positive inotropes may 
worsen fixed obstruction and are used with 
caution when treating CHF . • Anesthetic drugs 
that cause hypotension, arrhythmias, or cardiac 
depression should be avoided with severe SAS.
N/A
• Carvedilol (dogs, 0.5–1.5 mg/kg PO q12h). 
• Metoprolol tartrate (dogs, 0.5–1.5 mg/kg 
PO q12h).
  FOLLOW‐UP
• Monitor by ECG, Holter monitor, thoracic 
radiography, and echocardiography. 
• T reatment of complications such as CHF 
and arrhythmias may necessitate additional 
monitoring for renal/electrolyte, blood 
pressure, and rhythm disturbances.
N/A
Ventricular arrhythmias, syncope, myocardial 
infarction, sudden death, AI, mitral regurgi -
tation, endocarditis.EXPECTED COURSE AND PROGNOSIS
• Mildly affected dogs may have normal 
lifespan and quality without therapy.
• Severely affected dogs have limited lifespans 
and typically succumb to sudden death or CHF; 
in one study average lifespan for dogs with 
severe SAS on atenolol was about 4.5 years.
Increased risk of infective endocarditis.
SAS may not be immediately apparent at 
birth, but appears over first few weeks to 
months of life.
Contraindicated
SYNONYMS
Subaortic stenosis, discrete subaortic stenosis.
SEE ALSO
• Cardiomyopathy, Hypertrophic—Cats. 
• Cardiomyopathy, Hypertrophic—Dogs. 
• Congestive Heart Failure, Left‐Sided. 
• Endocarditis, Infective.
• AI = aortic insufficiency. • CHF = congestive 
heart failure. • LV = left ventricle. • LVOT = left 
ventricular outflow tract. • PDA = patent ductus 
arteriosus. • SAS = subvalvular aortic stenosis.
Caivano D, Dickson D, Martin M, et al. Murmur 
intensity in adult dogs with pulmonic and 
subaortic stenosis reflects disease severity. J 
Small Anim Pract 2018, 59(3):161–166.
Kienle RD, Thomas WP , Pion PD. The 
natural clinical history of canine congenital 
subaortic stenosis. J Vet Intern Med 1994, 
8(6):423–431.
Meurs KM, Lehmkuhl LB, Bonagura JD. 
Survival times in dogs with severe subvalvu-
lar aortic stenosis treated with balloon 
valvuloplasty or atenolol. J Am Vet Med 
Assoc 2005, 227(3):420–424.
Ontiveros ES, Fousse SL, Crofton AE, et al. 
Congenital cardiac outflow tract abnormali -
ties in dogs: prevalence and pattern of 
inheritance from 2008 to 2017. Front Vet Sci 
2019, 6(52), doi: 10.3389/fvets.2019.00052.
Stern JA, White SN, Lehmkuhl LB, et al. A 
single codon insertion in PICALM is 
associated with development of familial 
subvalvular aortic stenosis in Newfoundland 
dogs. Hum Genet 2014, 133(9):1139–1148.
Author  Joshua A. Stern
Consulting Editor  Michael Aherne
available online(continued)  Aortic Stenosis

108  Blackwell’s Five-Minute Veterinary Consult  
A
Aortic Thromboembolism
  BASICS
A thrombus or blood clot that is dislodged 
within the aorta, causing severe ischemia to 
the tissues served by that segment of aorta.
• Aortic thromboembolism (ATE) is 
commonly associated with myocardial disease 
in cats, most commonly hypertrophic cardio  - 
myopathy (HCM). It is theorized that abnormal 
blood flow (stasis) and a hypercoagulable state 
contribute to thrombus formation within the 
left atrium. The thrombus then embolizes 
distally to the aorta. The most common site 
of embolization is the caudal aortic 
trifurcation (hind legs). Other less common 
sites include the front legs, kidneys, 
gastrointestinal tract, or cerebrum.
• ATE in dogs typically is associated with 
neoplasia, sepsis, infectious endocarditis, 
Cushing’s disease, protein-losing nephropathy 
and enteropathy, or other hypercoagulable 
states. However, in one recent retrospective 
study, no concurrent condition was identified 
in 58% of dogs.
• Cardiovascular—most affected cats have 
advanced heart disease and left heart failure.
• Nervous/musculoskeletal—severe ischemia 
to muscles and nerves served by segment of 
occluded aorta causes variable pain and 
paresis. Gait abnormality or paralysis results 
in leg or legs involved.
GENETICS
HCM, a common associated disease, is likely 
heritable. Additionally, a family of domestic 
shorthair cats with remodeled HCM who all 
died of ATE has been reported.
• In a recent observation study of over 1000 
asymptomatic cats with HCM, nearly 12% 
developed ATE within 10 years after initial 
diagnosis. In two previous smaller case series 
of cats with clinical and preclinical HCM, 
12–16% presented with signs of ATE; only 
11–25% of cats had evidence of previously 
known heart disease.
• Rare in dogs.
N/A
Species
Cat, rarely dog.
Mixed-breed cats most commonly affected. 
Abyssians, Birmans, and ragdolls over -
represented in one study. In dogs, no breed 
predilection identified in United States; European study suggested cavalier King 
Charles spaniels may be overrepresented.
Age range—1–20 years. Median age—
approximately 8–9 years (cats); 8–10 years 
(dogs).
Cats—males > females (2 : 1). Dogs—no sex 
predilection in United States; European study 
suggested male predilection.
SIGNS
Presence of 5 “Ps” is helpful to remember 
classic clinical signs associated with ATE—
Pain, Paralysis or Paresis, Pulselessness, Pallor, 
and Poikilothermic (cold).
• Acute onset paralysis and pain—most 
common in cats. Vocalization and anxiety 
also common.
• Lameness or gait abnormality, typically of 
several weeks’ duration, more common in 
dogs.
• Tachypnea or respiratory distress common 
in cats.
• About 15% of cats may vomit prior to ATE.
• Usually paraparesis or paralysis of rear legs 
with signs of lower motor neuron injury. Less 
commonly, monoparesis of a front leg. In 
dogs, majority are paretic and ambulatory.
• Absent or diminished femoral pulses.
• Pain upon palpation of legs.
• Gastrocnemius muscle often becomes firm 
several hours after embolization.
• Cyanotic or pale nail beds and foot pads.
• Tachypnea/dyspnea and hypothermia are 
• Since commonly associated with heart 
disease in cats, cardiac murmur, arrhythmias, 
or gallop sound may be present.
CAUSES
• Cardiomyopathy (all types).
• Sepsis (dogs).
• Hyperadrenocorticism (dogs).
• Protein-losing nephropathy and 
enteropathy (dogs).
• In cats, cardiomyopathy, male sex, and 
gallop sound on exam are risk factors. 
Echocardiographic risk factors include 
enlarged left atrium, decreased left atrial 
function and left atrial appendage velocity, 
presence of spontaneous echocardiographic 
contrast (smoke) or left atrial thrombus, and 
restrictive left ventricular filling pattern.
• In dogs, hypercoagulable conditions, such 
as neoplasia, sepsis, endocarditis, protein-
losing nephropathies/enteropathies, and 
hyperadrenocorticism are risk factors.  DIAGNOSIS
Hind limb paresis secondary to spinal 
neoplasia, trauma, myelitis, fibrocartilaginous 
infarction, or intervertebral disc protrusion. 
These conditions resulting in spinal cord 
injury present with signs of upper motor 
neuron disease, whereas ATE patients present 
with signs of lower motor neuron disease.
• High creatine kinase due to muscle injury.
• Higher blood lactate and lower blood 
glucose in affected limbs compared to normal 
limbs.
• High aspartate aminotransferase and 
alanine aminotransferase due to muscle and 
liver injury.
• Stress hyperglycemia.
• High blood urea nitrogen and creatinine 
due to low cardiac output and possible renal 
emboli.
• Electrolyte derangements, due to low 
output and muscle damage, such as hypo -
calcemia, hyponatremia, hyperphosphatemia, 
and hyperkalemia, are not uncommon.
• Nonspecific CBC and urinalysis changes.
Routinely available coagulation profiles 
typically do not reveal significant 
abnormalities because hypercoagulability 
results from hyperaggregable platelets. In 
dogs, thromboelastrography may suggest 
hypercoagulable state with clot strength 
(increased maximum amplitude) or shortened 
clotting time (decreased R).
IMAGING
Radiography
• Cardiomegaly is common in cats.
• Pulmonary edema and/or pleural effusion 
in approximately 50% of cats.
• Rarely, a mass is seen in the lungs, suggestive 
of neoplasia.
• In cats, changes consistent with 
cardiomyopathy. HCM is most common, 
followed by restrictive or unclassified cardio  - 
myopathy, and then dilated cardiomyopathy.
• Most cases have severe left atrial enlarge -
ment (i.e., left atrial to aortic ratio of ≥2). 
Decreased left atrial function (fractional 
shortening) and decreased left atrial appendage 
velocity (<0.2 m/s).
• Left atrial thrombus or spontaneous 
echocardiographic contrast (smoke) may be 
seen.
• May be able to identify the thrombus and 
visualize lack of blood flow in the caudal aorta.

Canine and Feline, Seventh Edition  109
A
• Typically unnecessary to reach a diagnosis 
in cats, but often needed to reach a diagnosis 
in dogs.
ECG
• Sinus rhythm and sinus tachycardia most 
common. Less common rhythms include 
atrial fibrillation, ventricular arrhythmias, 
supraventricular arrhythmias, and sinus 
bradycardia.
• Left ventricular enlargement pattern and 
left ventricular conduction disturbances (left 
anterior fascicular block) are common.
Doppler Blood Pressure
No or diminished audible blood flow in 
affected limbs.
• Thrombus typically identified at caudal 
aortic trifurcation.
• Occasionally, left atrial thrombus seen.
• Emboli of kidneys, gastrointestinal tract, 
cerebrum, and other organs also may be seen.
  TREATMENT
Initially, cats with ATE should be treated as 
inpatients, as many have concurrent 
congestive heart failure (CHF) and require 
injectable drugs, in addition to being in 
considerable pain and distress.
• Fluid therapy is cautiously used, as most 
cats have advanced myocardial disease. If in 
CHF , IV fluids may not be necessary.
• Supplemental oxygen or thoracocentesis 
may be beneficial if in CHF .
• Initially, minimally handle affected legs. 
However, as reperfusion occurs, physical 
therapy (passive extension and flexion) may 
speed full recovery.
• Do not perform venipuncture on affected 
legs.
• Animals may have difficulty posturing to 
urinate and may need bladder expression to 
prevent overdistention or urine scald.
ACTIVITY
Restrict activity and stress.
DIET
Initially, most cats are anorexic; tempt with 
any type of diet to keep them eating and 
avoid hepatic lipidosis.
• Short- and long-term prognosis is poor in 
both dogs and cats.
• Many cats do not survive their initial 
episode of ATE; if they survive, the cat will 
often reembolize or die of CHF within a few 
months to one year. Most cats that survive an initial episode will be on some type of anti  - 
coagulant and heart failure medications that 
may require frequent reevaluation and an 
indoor lifestyle.
• Most cats that survive an initial episode will 
recover complete function to the legs; however, 
if ischemia is severe and prolonged, sloughing 
of parts of the distal extremities or persistent 
neurologic deficits may result. In one study, 
approximately 15% of cats had permanent 
neuromucscular abnormalities after surviving 
the initial ATE.
• Prognosis in dogs is generally poor, but may 
be better in dogs presenting with chronic (vs. 
acute) lameness and dogs treated appropriately 
with warfarin.
• Surgical embolectomy typically not 
recommended, since patients are high risk 
due to severe heart disease.
• Rheolytic thrombectomy has been used 
with limited success in a small number of cats 
with ATE.
Medical management focuses on (1) the 
thrombus, (2) analgesia, and (3) heart failure 
treatments (if needed).
Management of Thrombus
• Thrombolytic therapy (e.g., tissue 
plasminogen activator [TPA]) is used 
extensively in humans and infrequently in 
animals. These drugs are expensive and carry 
a significant risk for bleeding complications; 
to date, improved treatment efficacy is 
unproven and thus they are rarely used in 
general practice. TPA is theorized to be more 
beneficial if given early, ideally within the first 
few hours of the ATE.
• Unfractionated heparin is the preferred 
anticoagulant in general practice for initial 
management of feline ATE. Heparin has no 
effect on the established clot; however, it 
prevents further activation of the coagulation 
cascade. In either cat or dog, use an initial 
dose of 100–200 units/kg IV and then 
200–300 units/kg SC q8h. Alternatively, 
heparin can be continued as a constant rate 
infusion, at a dose of 25–35 units/kg/h. Some 
advocate titrating the dose to prolong the 
activated partial thromboplastin time (APTT) 
approximately twofold.
• Clopidogrel is an antiplatelet aggregation 
drug. A loading dose may be chosen for 
treatment of an acute ATE. The loading dose 
in the cat is 75 mg/cat PO once, and then a 
maintenance dose of 18.75 mg/cat (one-
fourth of a 75 mg tablet) PO q24h. The 
loading dose in the dog is approximately 
10 mg/kg once, and then a maintenance dose of 1 mg/kg q24h. Compared to aspirin, 
clopidogrel was superior in preventing 
reembolization, resulting in improved survival 
times in cats that had survived an ATE. The 
combination of unfractionated heparin and 
clopidogrel is commonly used for the manage  - 
ment of ATE in cats.
Other Options
• Aspirin is theoretically beneficial during 
and after an ATE event due to its antiplatelet 
effects. The dose in cats is an 81 mg tablet 
PO q48–72h. Vomiting and diarrhea are not 
uncommon. Some specialists advocate a mini 
dose of 5 mg/cat q72h. Antithrombotic dose 
recommendations for dogs range from 0.5 to 
2 mg/kg q24h. Always give aspirin with food.
• Warfarin, a vitamin K antagonist, is the 
anticoagulant most widely used in humans 
and has been proposed for prevention of 
reembolization in cats surviving an initial 
episode. The initial dose is 0.25–0.5 mg/cat 
PO q24h, or 0.05–0.2 mg/kg PO q24h in the 
dog. Overlap with heparin therapy for 3 days. 
The dose is then adjusted to prolong the 
prothrombin time (PT) approximately twice 
its baseline value, or to attain an international 
normalized ratio (INR) of 2 to 3. Long-term 
management with warfarin can be challenging 
because of frequent monitoring and dose 
adjustments in addition to bleeding complic -
ations. In one study, dogs treated 
appropriately with warfarin had a better 
clinical outcome.
• Low molecular weight heparin (LMWH) 
has recently been proposed for the long-term 
prevention of feline ATE. LMWH has a more 
predictable relationship between dose and 
response than warfarin and does not need 
monitoring or dose adjustments. It also has a 
lower risk of bleeding complications. The 
main disadvantages are high drug cost and the 
injectable route of administration. The two 
LMWHs that have been used in feline ATE 
are dalteparin (100–150 units/kg SC q8–24h) 
and enoxaparin (1 mg/kg SC q12–24h). The 
best dose is unknown. LMWH is usually 
started q24h due to cost. Some studies 
suggest q6h dosing is necessary for stable 
blood levels, but may increase bleeding risk. 
LMWH can be used as an adjunctive anti  - 
coagulant combined with clopidogrel.
• Rivaroxaban, a newer anticoagulant drug, 
is an inhibitor of activated clotting factor X 
and prothrombinase activity that has shown 
promise for treatment and prevention of 
arterial thromboembolism in both dogs and 
cats. Rivaroxaban has a more predictable 
anticoagulant effect than warfarin and does 
not require any monitoring or dose adjust -
ments. The cat dose is 1.25 mg/cat PO q24h. 
The dose recommended in dogs is 0.5–1 mg/
kg PO q24h. The main disadvantage of 
rivaroxaban is its high cost at the time of this 
writing. However, it has the advantage of a 
shorter half-time than clopidogrel if there is a (continued)  Aortic Thromboembolism

110  Blackwell’s Five-Minute Veterinary Consult  
A
need to discontinue the medication because 
of a bleeding complication or need to 
perform an invasive procedure. A clinical trial 
is currently ongoing to compare rivaroxaban 
and clopidogrel in cats that have survived an 
ATE.
• Buprenorphine in the cat is a useful and 
widely available drug for analgesia and 
sedation at a dose of 5–20  μg/kg IV, SC,  
or in cheek pouch q6–8h. For stronger 
analgesia, use fentanyl or hydromorphone. 
Butorphanol, while a good sedative, does  
not provide sufficient analgesia.
• Acepromazine may be cautiously used for 
its sedative and vasodilatory properties at a 
dose of 0.01–0.02 mg SC q8–12h. However, 
vasodilatory effects are mixed and therefore 
results are often variable.
N/A
• Anticoagulant therapy with heparin, 
warfarin, or thrombolytics may cause 
bleeding complications.
• Avoid a nonselective beta blocker such as 
propranolol as it may enhance peripheral 
vasoconstriction.
Warfarin may interact with other drugs, 
which may enhance its anticoagulant effects.
N/A
  FOLLOW-UP
• ECG monitoring while cat in hospital is 
helpful to detect reperfusion injury and 
hyperkalemia-related ECG changes. Look for 
loss of P-waves and widening of QRS 
complexes.
• Monitoring electrolytes and renal 
parameters periodically may be helpful to 
optimize management of cardiac disease.• Examine legs frequently to assess clinical 
response. Initially, APTT should be 
performed once daily to titrate heparin dose.
• If warfarin used, PT or INR is measured 
approximately 3 days after initiation of therapy 
and then weekly until desired anticoagulant 
effect reached. Thereafter, measure 3–4 times 
yearly or when drug regimen is altered.
Because of high rate of reembolization, 
prevention with either clopidogrel, aspirin, 
warfarin, or LMWH is strongly 
• Bleeding with anticoagulant therapy.
• Permanent neurologic deficits or muscular 
abnormalities in hind limbs may arise with 
prolonged ischemia.
• Recurrent CHF or sudden death.
• Reperfusion injury and death usually 
associated with hyperkalemic arrhythmias.
• Expected course is days to weeks for full 
recovery of function to legs.
• Prognosis, both short and long term, is 
poor in cats.
• In two large studies, ~60% of cats were 
euthanized or died during initial thrombo -
embolic episode. Long-term prognosis varies 
between 2 months and several years; however, 
average is a few months with treatment. 
Predictors of poorer prognosis include 
hypothermia ( <99 °F) and CHF . One study 
demonstrated median survival time of 77 
days in cats with CHF and 223 days in cats 
without CHF . Predictors of better prognosis 
include normothermia, single leg affected, 
and presence of motor function on initial 
exam.
• In dogs, the disease is rare and prognosis in 
general is also poor. One study suggested a 
better prognosis if the dog had chronic 
clinical signs and if treated with warfarin.
• Recurrence of ATE is common.  MISCELLANEOUS
N/A
None
N/A
SYNONYMS
• Saddle thromboembolism.
• Systemic thromboembolism.
SEE ALSO
• Cardiomyopathy, Dilated—Cats.
• Cardiomyopathy, Hypertrophic—Cats.
• Cardiomyopathy, Restrictive—Cats.
time.
• ATE = aortic thromboembolism.
• CHF = congestive heart failure.
• HCM = hypertrophic cardiomyopathy.
• INR = international normalized ratio.
• LMWH = low molecular weight heparin.
• TPA = tissue plasminogen activator.
Luis Fuentes V. Arterial thromboembolism: 
risks, realities and a rational first-line 
approach. J Feline Med Surg 2012, 
14(7):459–470.
Winter RL, Sedacca CD, Adams A, Orton 
EC. Aortic thrombosis in dogs: presenta-
tion, therapy, and outcome in 26 cases. J 
Vet Cardiol 2012, 14:333–342.
Author  Teresa C. DeFrancesco
available onlineAortic Thromboembolism  (continued)

Canine and Feline, Seventh Edition  111
A Apudoma
  BASICS
OVERVIEW
• T umors of endocrine cells that are 
capable of amine precursor uptake and 
decarboxylation (APUD) and secretion of 
peptide hormones. •  APUD cells are 
generally found in gastrointestinal tract and 
CNS. •  Hypergastrinemia from gastrin-
secreting tumors (gastrinomas) causes 
gastritis and duodenal hyperacidity, which 
can cause gastric ulceration, gastric mucosal 
hypertrophy, esophageal dysfunction (chronic 
reflux), and intestinal villous atrophy. 
• Polypeptide-secreting tumors 
(polypeptidomas) may not cause clinical 
signs, but high concentration of pancreatic 
polypeptide may cause gastric hyperacidity 
and gastrointestinal ulceration.
• Gastrinoma—rare in dogs, very rare in cats; 
age range 3–12 years, mean 7.5 years (dogs). 
• Pancreatic polypeptidoma—extremely rare 
in dogs.
SIGNS
• Vomiting. •  Weight loss. •  Anorexia. 
• Diarrhea. •  Lethargy, depression. 
• Melena. •  Abdominal pain. •  Hematemesis, 
hematochezia. •  Fever. •  Polydipsia. 
• Polypeptidomas may not cause any clinical 
signs.
Unknown
  DIAGNOSIS
• Conditions associated with hypergastrinemia, 
gastric hyperacidity, and gastrointestinal 
ulceration: ◦ Uremia. ◦ Hepatic failure. 
◦ Drug-induced ulceration, e.g., nonsteroidal 
anti-inflammatory drugs (NSAIDs) or 
steroids. ◦ Inflammatory gastritis. ◦ Stress-
induced ulceration. ◦ Mast cell disease.
• Normal or reflective of chronic disease or 
iron-deficiency anemia due to chronic 
gastrointestinal bleeding. •  Regenerative 
anemia. •  Increased blood urea nitrogen 
(BUN). •  Hypoproteinemia. •  Electrolyte 
abnormalities.OTHER LABORATORY TESTS
• Serum gastrin concentration—normal or 
high normal if gastrinoma. Antacid treatment 
increases serum gastrin, resulting in false-
positive diagnosis of gastrinoma; withdrawal of 
drugs for at least 7 days returns gastrin 
concentrations to baseline in dogs without 
gastrinoma. •  Induced gastrin secretion—
increased gastrin concentration after IV calcium 
gluconate or secretin suggests gastrinoma; rarely 
reported in veterinary medicine.
IMAGING
Abdominal ultrasound may demonstrate 
pancreatic mass or evidence of gastrointestinal 
ulceration/thickened gastric wall; frequently, 
the primary mass is too small to be detected.
• CT or MRI to identify pancreatic masses 
and/or metastatic lesions. •  Endoscopy with 
gastric and duodenal biopsy. •  Aspirate any 
detectable masses (rule out mast cell disease).
• Endoscopic biopsy—gastrointestinal 
ulceration. •  Histopathology of pancreatic 
tumors—islet cell tumor (not specific for 
hormone type). •  Immunocytochemical 
staining can aid specific diagnosis. •  Liver 
and regional lymph node biopsies may reveal 
  TREATMENT
• Most apudomas are malignant and have 
metastasized by the time of diagnosis; 
long-term control is difficult. •  Aggressive 
medical management can palliate signs for 
months to years. •  Surgical exploration and 
excisional biopsy/surgical debulking of a 
pancreatic mass are important both 
diagnostically and therapeutically. •  Medical 
management for gastric hyperacidity.
• Omeprazole—proton pump inhibitor; potent 
inhibitor of gastric acid secretion; preferred. 
• Histamine H2-receptor antagonists—
cimetidine, ranitidine, famotidine; decrease acid 
secretion by gastric parietal cells. •  Sucralfate—
adheres to ulcerated gastric mucosa and protects 
from acid; promotes healing by binding pepsin 
and bile acids and stimulating local prosta -
glandins. •  Octreotide–somatostatin analog—used successfully in 2 dogs and 1 cat with 
gastrinoma.
Because sucralfate may be less effective in an 
alkaline environment and may reduce 
absorption of other drugs, it should be given as 
a suspension, 1–2 hours prior to antacid drugs.
  FOLLOW-UP
• Physical examination and clinical signs are 
most useful measures of treatment effectiveness 
and disease progression. •  Gastroscopy can 
monitor progression of gastritis, but is not 
necessary. •  Abdominal radiography or 
ultrasound may detect development of 
abdominal masses. •  Monitoring of CBC and 
serum protein levels may aid in assessing 
gastrointestinal hemorrhage.
POTENTIAL COMPLICATIONS
Gastrointestinal perforations may occur with 
severe ulceration.
Survival time for gastrinoma ranges from 
weeks to years.
SEE ALSO
Gastroduodenal Ulceration/Erosion.
• APUD = amine precursor uptake and 
decarboxylation.
drug.
Hughes SM. Canine gastrinoma: a case study 
and literature review of therapeutic options. 
N Z Vet J 2006, 54(5):242–247.
Lane M, Larson J, Hecht S, Tolbert MK. 
Medical management of gastrinoma in a 
cat. JFMS Open Rep 2016, 
2(1):2055116916646389.
Author  Alyssa M. Sullivant
Consulting Editor  Patty A. Lathan
Thomas K. Graves.

112  Blackwell’s Five-Minute Veterinary Consult  
AArteriovenous Fistula and Arteriovenous Malformation
  BASICS
OVERVIEW
• Abnormal, low-resistance connections 
between an artery and a vein (systemic or 
portal) that bypass a capillary bed.
• Arteriovenous malformation (AVM)—
typically congenital, involving a vascular nidus, 
or complex network of communicating vessels.
• Arteriovenous fistula (AVF)—often 
acquired, direct, and singular connections.
• Large lesions cause marked drop in systemic 
vascular resistance and compensatory increase in 
cardiac output; this may cause circulatory volume 
overload and congestive heart failure (CHF).
• Variable location:
 ◦AVM most often reported in liver of dogs 
(termed arterioportal malformations/fistulas).
 ◦AVF more often in limbs or at sites of 
previous surgery/trauma.
• Dog and cat (rare in both).
• No specific age, breed, or sex—AVMs 
typically in younger animals; 15% of hepatic 
AVMs found in Labrador retrievers in a 
recent multicenter study.
SIGNS
• Depends on the lesion location (e.g., ascites 
with hepatic AVM).
• Often prior trauma to affected area with AVF .
• Warm, nonpainful swelling at site may be 
noted.
• Shunt may cause local organ dysfunction.
• Vary and depend on location.
• Signs of CHF (e.g., tachypnea, cough, 
exercise intolerance) may develop with 
chronic disease and high blood flow.
• Bounding pulses may be present due to 
high ejection volume and rapid runoff 
through AVM/AVF .
• Continuous murmur (bruit) at the site.
• Cautious compression of the artery proximal 
to the lesion abolishes the bruit. When blood 
flow is high, this may also elicit an immediate 
reflex decrease in heart rate (Branham’s sign).
• Edema, ischemia, and congestion of organs 
and tissues caused by high venous pressure in 
proximity of lesion.
• If the lesion is on a limb, pitting edema, 
lameness, ulceration, scabbing, and gangrene 
may result.
• Lesions near vital organs may cause signs 
associated with organ failure, e.g., ascites 
(liver), seizures (brain), paresis (spinal cord).
• AVM is rare; frequently congenital.• Acquired AVF typically results from local 
vascular damage via trauma, surgery, veni  - 
puncture, perivascular injection, or neoplasia.
  DIAGNOSIS
• Peripheral lesions (limb, ear) may look like 
a mass.
• Vascular aneurysm or pseudoaneurysm.
• Atypical clinical findings, depending on 
location, may suggest other disease processes; 
AVF/AVM may be a late diagnostic consid- 
eration.
May reflect damage to systems in vicinity of 
lesion, i.e., hepatic, renal, or other organ 
dysfunction.
N/A
IMAGING
Cardiomegaly and pulmonary overcirculation 
with hemodynamically significant lesions. 
Microhepatica and loss of abdominal detail in 
hepatic AVMs.
Ultrasonography
• Lesions appear as cavernous, often tortuous, 
vascular structures.
• May observe high-velocity, turbulent flow 
on Doppler ultrasound.
• Hepatofugal flow in portal vein (away from the 
liver) nearly always apparent in hepatic AVM.
• Echocardiography may show four-chamber 
dilation and functional atrioventricular valve 
regurgitation due to increased circulating 
blood volume.
Cross-sectional Imaging
CT or MRI can aid in diagnosis, particularly 
when contrast is timed to highlight vascular 
anatomy.
Angiography
Selective angiography is the optimal test and is 
performed at time of intervention, if transcath -
eter therapy is pursued; digital subtraction 
angiography can improve visualization.
N/A
  TREATMENT
• Surgery can be difficult, labor-intensive, 
and may require blood transfusion. Ligation 
or division of an AVF is often curative; en bloc  resection of an AVM is necessary 
for cure.
• T ranscatheter therapies with coils, 
devices, or glue are newer treatment 
options; potential advantages include less 
invasive therapy and intravascular access to 
remote lesions. Coils or occlusive devices 
are often sufficient for treatment of AVF; 
AVMs have been terminated by glue 
embolization of the arterial nidus, and 
more recently by embolization or ligation 
of the dominant outflow vein, which 
appears to limit shunt flow.
• Lesions may recur. In some cases, staged 
procedures or surgical removal of the affected 
limb or organ (e.g., amputation, liver 
lobectomy) may be necessary.
• Depend on site of lesion and secondary 
clinical features.
• Medical treatment for CHF or other organ 
dysfunction may be required before surgery.
Avoid excessive fluid administration; patients 
are often volume overloaded and in a high 
cardiac output state.
  FOLLOW-UP
Postoperative reevaluation and imaging 
needed to determine whether the lesion has 
recurred and if organ dysfunction has 
resolved.
SEE ALSO
Congestive Heart Failure, Left-Sided.
• AVF = arteriovenous fistula.
• AVM = arteriovenous malformation.
Weisse C, Berent A, eds. Veterinary Image-
Guided Interventions. Ames, IA: Wiley-
Blackwell, 2015.
Author  Brian A. Scansen

Canine and Feline, Seventh Edition  113
A Arteriovenous Malformation of the Liver
  BASIC
OVERVIEW
• Intrahepatic arteriovenous (AV) malfor­
mations (also referred to as AV fistulae) are 
communications between proper hepatic 
arteries and intrahepatic portal veins; this 
anatomic union results in hepatofugal (away 
from the liver) splanchnic circulation.
• Blood flows directly from a hepatic artery 
into portal vasculature retrograde into the 
vena cava through multiple acquired porto  ­ 
systemic shunts (APSS).
• Associated with ascites.
• Uncommon, usually congenital, but may be 
acquired (surgical injury, trauma, neoplasia).
• Dogs, less common in cats.
• Age­related presentation (congenital): <2 years.
• No sex or breed predilection.
SIGNS
Vague or acute illness; present for signs caused 
by portal hypertension and APSS—ascites 
and hepatic encephalopathy (HE).
• Dogs may have a normal transition to 
growth foods, unlike portosystemic vascular 
anomalies (PSVA) that demonstrate HE.
• May have an acute onset of ascites or HE.
• Vague signs include lethargy, anorexia, 
vomiting, diarrhea, weight loss, polydipsia, 
dementia, abdominal distention, and uroliths 
causing obstructive uropathy.
• Lethargic, poor body condition, ascites; 
enlarged liver lobe containing the AV 
malformation; rarely palpated on initial 
• Rarely, bruit auscultated over AV 
malformation.
• Usually congenital vascular malformations 
(single or multiple vessels) reflecting failed 
differentiation of common embryologic anlage.
• Rare—secondary to abdominal trauma, 
inflammation, neoplasia, surgical interventions, 
or diagnostic procedures (e.g., liver biopsy).
• Portal hypertension—reflects arterialization 
of valveless portal system—establishing 
APSS.
  DIAGNOSIS
• CNS signs—infectious disorders (e.g., 
distemper); toxicity (e.g., lead); hydro­cephalus; idiopathic epilepsy; metabolic 
disorders (e.g., hypoglycemia, hypokalemia, 
or hyperkalemia); HE (e.g., acquired liver 
disease or PSVA).
• Abdominal effusion—pure transudate 
(ascites; protein ­losing nephropathy, 
protein ­losing enteropathy, liver disease); 
modified transudate (congenital cardiac 
malformations, right ­sided heart failure, 
pericardial tamponade, supradiaphragmatic 
vena caval obstruction, neoplasia, portal vein 
thrombosis); hemorrhage.
• Portal hypertension—chronic hepatic 
disease, ductal plate malformations/
congenital hepatic fibrosis, noncirrhotic or 
idiopathic portal hypertension, cirrhosis, 
portal thrombi.
• Erythrocyte microcytosis (APSS), target 
cells.
• Hypoalbuminemia with normal or low 
serum globulins; alkaline phosphatase (ALP) 
and alanine aminotransferase (ALT) activity 
normal or moderately increased; variable low 
blood urea nitrogen (BUN); hypocholestero­
lemia; anicteric.
• Hyposthenuria or isosthenuria.
• Ammonium biurate crystalluria.
• Coagulation tests—variable, may be 
normal; low protein C activity reflects APSS.
• Total serum bile acids—preprandial values 
variable, postprandial values increased; classic 
shunting pattern.
• Plasma ammonia—usually increased, 
inferred by ammonium biurate crystalluria.
• Peritoneal fluid—pure transudate (total 
protein <2.5 g/dL) or modified transudate.
IMAGING
• Abdominal effusion.
• Microhepatia or normal ­sized liver due to 
enlarged lobe with AV malformation.
• Renomegaly.
• Normal thorax.
• Liver lobe with AV malformation—large 
compared to most other liver lobes that are 
atrophied due to portal hypoperfusion.
• Tortuous anechoic tubules represent AV 
structure with unidirectional pulsating or 
turbulent flow on color ­flow Doppler.
• Hepatic artery and/or portal vein branches 
may appear tortuous.
• Hepatofugal portal flow (away from the 
liver)—through APSS.
• Urolithiasis—urinary bladder or renal pelvis.
• Rule out portal thrombosis (luminal filling 
defect, abrupt blood flow termination).Radiographic Contrast Angiography
• Not indicated in most cases.
• Venous portography—only confirms APSS.
• Hepatic arteriography—required to confirm 
AV communication (celiac trunk or anterior 
mesenteric artery contrast injection).
Multisector CT
Noninvasive contrast imaging of hepatic 
vasculature; arterial and venous phases; three ­ 
dimensional reconstruction illustrates AV 
malformation, large liver lobe, atrophied liver.
Rule out right ­sided heart disease, pericardial 
disease, and vena caval occlusion.
• Multisector CT and exploratory laparotomy.
• Liver biopsy—collect samples from affected  
and unaffected  liver lobes; “normal” liver often 
demonstrates severe vascular arterialization 
(more severe than associated with PSVA).
  TREATMENT
Inpatient —treat HE and ascites prior to 
surgical approach or percutaneous selective 
acrylamide embolization.
• Diet—restrict nitrogen intake to ameliorate 
HE and hyperammonemia; restrict sodium to 
attenuate ascites formation.
• HE—resolve endoparasitism, electrolyte 
and hydration disturbances, treat infections, 
initiate treatments to alter enteric uptake and 
formation of HE toxins (see Hepatic 
Encephalopathy).
• Ascites —mobilize by restricting activity and 
sodium intake and instituting dual diuretic 
therapy (furosemide and spironolactone); 
reserve therapeutic abdominocentesis for 
tense ascites impairing ventilation, nutrition, 
sleep, or recumbent posture (see Hypertension, 
Portal; Portosystemic Shunting, Acquired; 
and below).
• Resection of liver lobe containing AV 
malformation is complicated by coexistence 
of additional hepatic vascular malformations; 
clinical cure possible but unlikely.
• Percutaneous selective acrylamide vascular 
embolization; complicated by risk of thrombo  ­ 
embolism of additional vasculature; 
temporary improvement, but treatment may 
be curative.
• Multiple microscopic vascular malformations 
continue portal hypertension and APSS.
• Do not ligate APSS nor band the vena cava.

114  Blackwell’s Five-Minute Veterinary Consult  
A
Hepatic Encephalopathy
See Hepatic Encephalopathy
Ascites
• Restrict sodium intake.
• Furosemide (0.5–2 mg/kg PO IM or IV 
q12–24h)—combine with spironolactone.
• Spironolactone (0.5–2 mg/kg PO q12h)—
double initial dose as loading dose once.
• Chronic diuretic therapy—individualized 
to response, 4 ­ to 7­day assessment intervals 
used to titrate dose to response, avoiding 
hydration, electrolyte, and HE complications.
• Diuretic ­resistant ascites—may require 
therapeutic abdominocentesis; to initiate 
diuresis.
• Vasopressin V2 receptor antagonists newly 
available may control ascites accumulation. 
(See Portosystemic Shunting, Acquired.)
Bleeding Tendencies
See Coagulopathy of Liver Disease.
Gastrointestinal Hemorrhage
• Histamine type-2 receptor antagonists  
(famotidine 0.5–2.0 mg/kg PO, IV, or SC 
q12–24h); or HCl pump inhibitors  
(omeprazole 1.0 mg/kg/24h PO or 
pantoprazole 1.0 mg/kg/24h IV; omeprazole 
may induce p450 cytochrome ­associated drug interactions and may have a 24–48h delayed 
onset of action; some clinicians recommend 
chronic treatment to minimize GI bleeding 
and ulceration that may be chronic problems).
• Gastroprotectant —sucralfate: 0.25–1.0 g/10 
kg PO q8–12h; titrate to effect, beware of 
drug interactions as sucralfate may bind other 
medications, reducing bioavailability.
• Eliminate endoparasitism .
Avoid drugs dependent on hepatic biotrans­
formation or first ­pass hepatic extraction 
(reduced by APSS) or that react with 
γ­aminobutyric acid (GABA) ­benzodiazepine 
receptors because of propensity for HE.
  FOLLOW-UP
Biochemistry—initially monthly until 
stabilized after surgery or AV malformation 
embolization, thereafter quarterly; monitor 
for hypoalbuminemia, infection, optimization 
of HE management, and control of ammo­
nium biurate crystalluria.
• Prognosis fair if patient survives surgical 
resection of AV malformation or 
embolization.• Most patients require indefinite nutritional 
and medical management (HE, ascites) 
because of coexisting microscopic vascular 
malformations across the liver; APSS persists 
requiring continued management of HE.
SEE ALSO
• Ascites.
• Coagulopathy of Liver Disease.
• Hepatic Encephalopathy.
• Hypertension, Portal.
• Portosystemic Shunting, Acquired.
• Portosystemic Vascular Anomaly, 
Congenital.
• APSS = acquired portosystemic shunt.
• AV = arteriovenous.
• GABA = γ­aminobutyric acid.
• HE = hepatic encephalopathy.
• PSVA = portosystemic vascular anomalies.
Author  Sharon A. Center
Consulting Editor  Kate HolanArteriovenous Malformation of the Liver  (continued)

Canine and Feline, Seventh Edition  115
A
  BASICS
Osteoarthritis (OA) or degenerative joint 
disease is a chronic and progressive disease 
that leads to loss of articular cartilage and 
ultimately failure of the joint. OA is 
characterized as a noninfectious disorder of 
diarthrodial (synovial) joints, such that the 
disease process involves the entire joint, not 
just the articular cartilage. It is due to both 
primary (idiopathic) and secondary causes.
• Ebb and flow characterization with periods of 
calmness followed by periods of exacerbation 
of clinical signs (flare-ups).
• OA initiated by mechanical stress—  traumatic 
injury, instability, abnormal conformation, 
abnormal activity, etc.
• Inflammatory mediators and free radicals 
such as metalloproteinases, serine proteases, 
cysteine protease enzymes, and reactive 
oxygen species are released from damaged 
chondrocytes and synovium, resulting in 
breakdown of extracellular matrix of articular 
cartilage, causing collagen degradation and 
loss of collagen cross-linking.
• Collagen synthesis is altered, resulting in 
decreased collagen/proteoglycan interaction 
and reduced hydrophilic matrix properties.
• Extracellular matrix further compromised 
by increased breakdown of proteoglycans 
along with manufacture of poorer-quality 
proteoglycans.
• Nitric oxide released along with other free 
radicals, which mediates cartilage breakdown 
and supports chronic inflammation. 
Chondrocyte apoptosis facilitated by 
cyclooxygenase-2 enzymes and oxidative stress.
• Synovitis is driving force of the inflamma-
tory cascade in OA, in addition to resulting in 
decreased viscosity of synovial fluid, reducing 
lubrication.
• Poorer-quality synovial fluid reduces oxygen 
and nutrient supply to chondrocytes as well as 
waste removal.
• Subchondral bone becomes sclerotic, 
worsening loading qualities of bone and 
overlying cartilage.
• Pain of OA results from distention of the 
joint capsule and stimulation of pain 
receptors, inflammation of synovium, 
increased mechanical loading of subchondral 
bone, alteration of function of surrounding 
tendons and ligaments, as well as develop-
ment of periarticular fibrosis.
• The result of these processes is progressive 
cartilage degradation ranging from fibrillation 
to deep fissuring of cartilage. Full-thickness 
cartilage loss can eventually occur.
• Periarticular fibrosis occurs, resulting in a 
reduction of joint motion (and pain), leading to poorer vascularity of synovial membrane as 
well as lack of functionality of synovium due 
to lack of motion in joint.
• Osteophytes and enthesiophytes develop 
around and within joint to increase load-
bearing surface area.
• These changes reduce functionality and 
may eventually lead to ankylosis.
Musculoskeletal—diarthrodial joints.
GENETICS
• Primary OA rare, occurring more com-
monly in cats or in smaller (manus, pes) 
joints of dogs.
• Dogs—causes of secondary OA are varied, 
including hip and elbow dysplasia, osteo-
chondritis dessicans (OCD), patellar 
luxations, congenital shoulder luxation, 
Legg-Perthes, cranial cruciate ligament 
rupture, intra-articular fractures, obesity, as 
well as many other causes.
• Cats—causes of secondary OA are patellar 
luxation, hip dysplasia, obesity, and arthro  - 
pathy.
• Dog—very common; 20% of dogs older 
than 1 year have some degree of OA.
• Cat—90% of cats over 12 years of age had 
evidence of OA on radiographs.
• Clinical problems are more prevalent in 
larger, overweight, and very active animals.
• Primary OA is rare.
Species
• Secondary OA due to congenital disorders 
(OCD, hip dysplasia) seen in immature 
animals; some present with OA signs when 
mature (hip and elbow dysplasia).
• Secondary to trauma—any age.
SIGNS
• Dogs—decreased activity level, unwilling to 
perform certain tasks; intermittent lameness 
or stiff gait that slowly progresses; possible 
history of joint trauma, OCD, or develop-
mental disorders; may be exacerbated by 
exercise, long periods of recumbency, and 
cold weather.
• Cats—overt lameness may not be seen. 
Reduction in activity, reluctance to jump, 
unkempt appearance, difficulty accessing 
litter box, and increased irritability.
• Stiff-legged or altered gait or nonuse of leg.
• Decreased range of motion.
• Crepitus.
• Joint swelling (effusion and/or thickening 
of the joint capsule).
• Joint pain.• Joint instability.
CAUSES
• Primary—no known cause.
• Secondary—results from initiating cause: 
abnormal wear on normal cartilage (e.g., joint 
instability, joint incongruity, trauma to 
cartilage or supporting soft tissues, obesity) 
or normal wear on abnormal cartilage 
(e.g., osteochondral defects).
• Working, athletic, and obese dogs place 
more stress on their joints.
• Dogs with disorders that affect collagen or 
cartilage (Cushing’s disease, diabetes mellitus, 
hypothyroidism, hyperlaxity, prolonged 
steroid use).
  DIAGNOSIS
• Neoplastic (synovial sarcoma; rarely, 
chondrosarcoma; osteosarcoma).
• Septic arthritis (caused by bacteria; 
spirochetes; L forms in cats; Mycoplasma ; 
Rickettsia ; Ehrlichia ; viruses such as feline 
calicivirus; fungi and protozoa).
• Immune-mediated arthritis (erosive vs. 
nonerosive).
• Other musculoskeletal conditions that 
cause lameness.
• Neurologic conditions causing lameness or 
decreased activity/weakness.
• Coombs’ test, antinuclear antibody (ANA), 
and rheumatoid factor may help to rule out 
immune-mediated arthritis.
• Serum titers for Borrelia , Ehrlichia , and 
Rickettsia  to evaluate for infectious arthritis.
IMAGING
• Radiographic changes—include joint capsular 
distention, osteophytosis, enthesophytosis, 
soft-tissue thickening, and narrowed joint spaces. 
In severely affected patients: subchondral 
sclerosis and intra-articular calcified bodies 
(joint mice).
• Radiographic severity often does not 
correlate with clinical severity.
• Stress radiography may identify underlying 
instability and accentuate joint incongruity 
(e.g., distraction index, passive hip laxity of 
coxofemoral joint is predictive of hip OA).
• Bone nuclear scintigraphy can assist in 
localizing subtle OA.
• Arthroscopy can allow direct observation of 
cartilage and characterization by Modified 
Outerbridge Score.
• Arthrocentesis and synovial fluid analysis—
cell counts are normal or slightly increased 
(<2,000–5,000 cells/mL) predominantly Arthritis (Osteoarthritis)

116  Blackwell’s Five-Minute Veterinary Consult  
A
mononuclear (macrophages) and occasional 
synovial lining cells.
• Bacterial culture of synovial fluid or 
synovium—negative.
• Biopsy of synovial tissue to rule out 
neoplasia or immune-mediated arthropathy 
(lymphocytic plasmacytic synovitis, systemic 
lupus erythematosus).
• Fibrillation or erosion of articular cartilage.
• Eburnation and sclerosis of subchondral bone.
• Thickening and fibrosis of joint capsule.
• Synovial fluid can be grossly normal to thin 
and watery, usually increased volume.
• Synovial villous hypertrophy and hyperplasia.
• Osteophytes and enthesiophytes at joint 
capsule attachments and adjacent to the joint.
• Neovascularization or pannus in severe 
cases over joint surfaces.
  TREATMENT
• Medical—usually tried initially.
• Surgical options—to improve joint geometry 
or remove bone-on-bone contact areas through 
total joint arthroplasty, ostectomy, or joint fusion.
• Physical rehabilitation—very beneficial 
during periods of flare-ups.
• Maintaining or increasing joint motion—
active and passive range of motion exercises, 
stretching, massage, therapeutic exercises, and 
hydrotherapy.
• Pain management—cold and heat therapy, 
transcutaneous electrical stimulation (TENS), 
and acupuncture.
• Muscle tone/strengthening—daily leash 
walking, incorporation of inclines/declines, 
stair ascent and stair descent, walking on 
uneven terrain, open water swimming, 
underwater and land treadmill.
• Maintenance of a lean body weight through 
both diet and daily exercise.
ACTIVITY
• During periods of calmness, daily leash 
walks to work up to twice-daily level flat 
ground for 20 minutes before incorporation 
of increased time or terrain.
• Limitation of daily activity that minimizes 
aggravation of clinical signs during periods of 
flare-up (avoidance of running, chasing, 
jumping, and playing).
DIET
• Weight reduction for obese patients—
decreases stress placed on arthritic joints. 
Begin by feeding 60% of calories needed to 
maintain current body weight.
• Omega n-3 fatty acids decrease production of 
certain prostaglandins and modulate inflamma -
tion. Dosage should be 150–175 mg/kg DHA/
EPA daily.CLIENT EDUCATION
• Medical therapy is palliative and the 
condition is likely to progress.
• Describe identifying signs of flare-ups and 
importance of getting it under control 
quickly.
• Discuss management options, daily 
exercise, activity level, and diet.
• Arthrotomy—used to remove aggravating 
causes (e.g., fragmented coronoid process, 
ununited anconeal process, osteochondral flaps).
• Arthroscopy—used to diagnose and remove 
aggravating causes.
• Reconstructive procedures—used to 
eliminate joint instability and correct 
anatomic problems (cruciate ligament 
rupture, patella luxation, angular deformity).
• Joint removal—femoral head and neck 
ostectomy, temperomandibular joint arthro- 
plasty.
• Joint replacement—total hip replacement is 
widely used, total elbow and stifle replace-
ment are used with less frequency, total ankle 
and shoulder replacment are experimental 
and used infrequently at this time.
• Joint fusion (arthrodesis)—in selected 
chronic cases and for joint instability, 
complete or partial; carpus, hock: generally 
excellent outcome; shoulder, elbow, stifle: less 
predictable outcome.
(NSAIDs)
• Inhibit prostaglandin synthesis through 
cyclooxygenase enzymes.
• Deracoxib (3–4 mg/kg PO q24h, chewable).
• Carprofen (2.2 mg/kg PO q12h or q24h).
• Meloxicam (load 0.2 mg/kg PO, then 
0.1 mg/kg PO q24h, liquid).
• Tepoxalin (load 20 mg/kg, then 10 mg/kg 
PO q24h).
• Cats—meloxicam (0.1 mg/kg PO q24h, 
liquid) or robenacoxib (1 mg/kg PO q24h for 
3 days).
• Inhibit prostaglandin synthesis at receptor 
specific sites.
• Grapiprant (2.0 mg/kg PO q24h, chewable).
Disease-Modifying Osteoarthritis Agents 
(DMOAs)
• Host of products, many with little produc -
tion oversight so effects vary widely. Supply 
polysulfated glycosaminoglycan (PSGAG) 
molecules to repair and regenerate cartilage.
• Adequan®—clinical study in dogs with hip 
dysplasia; 4.4 mg/kg IM every 3–5 days for 8 
injections had positive, temporary effect.
• Glucosamine and chondroitin sulfate—oral 
Cosequin®, oral methylsulfonylmethane (MSM), mixtures with MSM, or other 
supplements (e.g., Dasuquin® Advanced, 
GlycoFlex® 2, Synflex).
• NSAIDs must not be given with steroids.
• Acetaminophen must not be given to cats.
• NSAIDs may cause gastric ulceration.
• Cyclooxygenase-2 (COX-2)-selective drugs 
may interfere with liver function when used 
outside of dosage range
• When switching NSAIDs—wait 3 days for 
washout before starting new drug.
Steroids with NSAIDS.
• Free-radical scavengers.
• Amantadine (3–5 mg/kg PO q24h)—best 
used in combination with another analgesic 
such as NSAID. Only analgesic (other than 
NSAID) with scientific evidence for usage 
with OA.
• Gabapentin (5–10 mg/kg PO q8-12h)—no 
scientific evidence for usage with OA.
• Codeine (1–2 mg/kg PO q 8–12h)—no 
scientific evidence for usage with OA; 
suggested for short-term use during flare-ups.
• Glucocorticoids—inhibit inflammatory 
mediators and cytokines; however, chronic 
use delays healing and initiates damage to 
articular cartilage; potential systemic side 
effects documented; goal is low dose (dogs, 
0.5–2 mg/kg; cats, 2–4 mg/kg) q48h.
• Prednisone—initial dose 1–2 mg/kg PO q24h 
for dogs and 4 mg/kg PO q24h for cats.
• T riamcinolone hexacetonide—intra-articular 
injection of 5 mg in dogs showed a protective 
and therapeutic effect in one model.
• Hyaluronic acid—intra-articular injection 
(15–30 mg/joint) used as a series of 3 
separated by 1 week or in combination 
with an intra-articular steroid.
• Platelet-rich plasma—intra-articular 
injection to decrease inflammatory mediators; 
many patients need more than 1 injection 
separated by 2 weeks; weak scientific evidence 
for efficacy.
  FOLLOW-UP
• During flare-up recheck 2 weeks later; pain 
should be better controlled at this time; then 
recheck every 4–6 weeks until flare-up under 
control.
• Recheck OA patients every 4–6 months 
for life.
• Any clinical deterioration could indicate a 
flare-up—need to change drug selection or 
dosage; may indicate need for intra-articular Arthritis (Osteoarthritis)  (continued)

Canine and Feline, Seventh Edition  117
A
injection, formal rehabilitation therapy, or 
surgical intervention.
Early identification of predisposing causes 
and prompt treatment to help reduce 
progression of secondary conditions, e.g., 
surgical removal of osteochondral lesions.
• Slow progression of disease likely.
• Some form of medical or surgical treatment 
usually allows a good quality of life when 
managed appropriately and aggressively.
SYNONYMS
• Degenerative arthritis.
• Degenerative joint disease.
• Osteoarthritis.
• Osteoarthrosis.
• COX-2 = cyclooxygenase-2.
• DMOA = disease-modifying osteoarthritis agent.• MSM = methylsulfonylmethane.
drug.
• OA = osteoarthritis.
• OCD = osteochondritis dessicans.
• PSGAG = polysulfated glycosaminoglycan.
Aragon CL, Hofmeister EH, Budsberg SC. 
Systematic review of clinical trials of 
treatments for osteoarthritis in dogs. J Am 
Vet Med Assoc 2007, 230(4):514–521.
Baime MJ. Glucosamine and chondroitin 
sulphate did not improve pain in osteoar-
thritis of the knee. Evid Based Med 2006, 
11(4):115.
Budsberg SC, Bartges JW. Nutrition and 
osteoarthritis in dogs: does it help? Vet Clin 
North Am Small Anim Pract 2006, 
36(6):1307–1323.
Glass GG. Osteoarthritis. Dis Mon 2006, 
52(9):343–362 (human review).
Hampton T. Efficacy still uncertain for widely 
used supplements for arthritis. J Am Med 
Assoc 2007 297(4):351–352.
Herrero-Beaumont G, Ivorra JA, Del Carmen 
T rabado M, et al. Glucosamine sulfate in 
the treatment of knee osteoarthritis symptoms: a randomized, double-blind, 
placebo-controlled study using acetami-
nophen as a side comparator. Arthritis 
Rheum 2007, 56(2):555–567.
Johnston SJ. Osteoarthritis joint anatomy, 
physiology and pathobiology. Vet Clin 
North Am 1997, 27:699–723.
Mlacnik E, Bockstahler BA, Muller M, et al. 
Effects of caloric restriction and a moderate 
or intense physiotherapy program for 
treatment of lameness in overweight dogs 
with osteoarthritis. J Am Vet Med Assoc 
2006, 229(11):1756–1760.
Van Der Kraan PM, Van Den Berg WB. 
Osteophytes: relevance and biology. 
Osteoarthritis Cartilage 2007, 15(3):237–244.
Author  David Dycus
Walter C. Renberg.
available online(continued)  Arthritis (Osteoarthritis)

118  Blackwell’s Five-Minute Veterinary Consult  
A
  BASICS
Pathogenic microorganisms within the closed 
space of one or more synovial joints.
• Usually caused by contamination associated 
with traumatic injury (e.g., a direct penetrating 
injury such as bite, gunshot wound, foreign 
object), a sequela to surgery, arthrocentesis or 
joint injection, hematogenous spread of 
microorganisms from a distant septic focus, 
or less commonly the extension of primary 
osteomyelitis. • Primary sources of 
hematogenous infection—  urogenital, 
integumentary (including ears and anal sacs), 
respiratory, cardiac, and gastrointestinal 
systems.
Musculoskeletal—usually affects one joint.
GENETICS
N/A
Relatively uncommon cause of monoarticular 
arthritis in dogs and cats.
May be an increased incidence in areas with 
endemic Lyme disease.
Species
• Most common in dogs. • Rare in cats.
Any; medium to large breeds—most 
commonly German shepherds, Dobermans, 
and Labrador retrievers.
Any age; usually between 4 and 7 years. 
Hematogenous—more common in 
immature animals.
Male
SIGNS
Always consider the diagnosis in patients 
with acute, monoarticular lameness 
associated with soft tissue swelling, heat, 
and pain.
• Lameness—acute onset most common, 
but can present as chronic lameness. 
• Lethargy. • Anorexia. • May report 
previous trauma—dog bite, penetrating 
injury, prior surgery or other invasive 
procedure of the joint.
• Monoarticular lameness, rarely polyarticular. 
• Joint pain and effusion—commonly carpus, 
stifle, hock, shoulder, or cubital joint.• Localized joint heat. • Decreased range of 
motion. • Local lymphadenopathy. • Pyrexia.
CAUSES
• Aerobic bacterial organisms—most common: 
staphylococci, streptococci, coliforms, and 
Pasteurella . • Anaerobic organisms—most 
common: Propionibacterium , Peptostreptococcus , 
Fusobacterium , and Bacteroides . • Spirochete—
Borrelia burgdorferi . • Mycoplasma . • Fungal 
agents— Blastomyces , Cryptococcus , and 
Coccidioides . • Rickettsial —Anaplasma , 
Ehrlichia , Rickettsia . • Leishmania .
• Feline calicivirus.
• Predisposing factors for hematogenous 
infection—diabetes mellitus, hypoadreno­
corticism (Addison’s disease), immuno­
suppression. • Penetrating trauma to the joint 
including surgery. • Existing osteoarthritis or 
other joint damage. • Intra ­articular 
injection, particularly if steroid injected.
  DIAGNOSIS
• Osteoarthritis. • T rauma. • Immune ­
mediated arthropathy. • Postvaccinal transient 
polyarthritis. • Greyhound polyarthritis. 
• Feline progressive polyarthritis. • Crystal ­
induced joint disease. • Synovial sarcoma.
• Hemogram—inflammatory left shift in 
some cases. • Other results normal.
Serologic testing for specific pathogens.
IMAGING
• Early disease—may reveal thickened and 
dense periarticular tissues; may see evidence 
of synovial effusion. Often difficult to 
diagnose early disease radiographically. • Late 
disease—reveals bone destruction, osteolysis, 
irregular joint space, discrete erosions, and 
periarticular osteophytosis.
Synovial Fluid Analysis
• Increased volume. • T urbid fluid. 
• Decreased viscosity. • Decreased mucin 
clot reaction. • Make slides immediately; 
if additional fluid is obtained, place in EDTA 
tube. • Elevated white blood cell (WBC) 
count—i.e., >80% neutrophils with  
>40,000/mm3 (normal joint fluid <10% 
neutrophils and <3,000/mm3) • Neutrophils 
may show degenerative changes (chromatolysis, 
vacuolation, nuclear swelling, loss of 
segmentation). • Neutrophils with 
phagocytosed bacteria—definitive diagnosis 
or bacteria in the synovial fluid.Synovial Fluid Culture
• Positive culture is definitive but not 
necessary for diagnosis; negative culture does 
not rule out infection. • Must be collected 
aseptically; requires heavy sedation or 
general anesthesia.  • Place fluid sample in 
aerobic and anaerobic culturettes and in 
blood culture medium.  • Use 1 : 9 dilution 
of synovial fluid to blood culture media.  
• Culturette samples—cultured immediately 
upon arrival at the laboratory.  • Blood 
culture medium—reculturing after 24 hours 
of incubation increases accuracy by 50% and 
is the preferred method.  • Mycoplasma , 
bacterial L ­forms, and protozoa require 
specific culture procedures—contact 
laboratory prior to sample collection.
Other
• Synovial biopsy—to rule out immune ­
mediated joint disease; no more effective than 
incubated blood culture medium for growing 
bacterial organisms. • Blood and urine 
cultures if hematogenous source is suspected.
• Synovium—thickened; discolored; often 
very proliferative. • Histology—evidence of 
hyperplastic synoviocytes. • Increased 
numbers of neutrophils, macrophages, and 
fibrinous debris. • Cartilage—loss of 
proteoglycan, destruction of articular surface, 
pannus formation.
  TREATMENT
• Inpatient—initial stabilization; initiate 
systemic antibiotic therapy as soon as fluid is 
obtained for bacterial culture; consider joint 
drainage/lavage as soon as possible to minimize 
intra­articular injury. • Analgesia with anti ­ 
inflammatory medications if appropriate, and 
intravenous opioid. • Identify and treat source 
if hematogenous spread is suspected. 
• Outpatient—long ­term management.
Alternating heat and cold packing—beneficial 
in promoting increased blood flow and 
decreased swelling.
ACTIVITY
Restricted until resolution of symptoms.
DIET
N/A
• Discuss probable cause. • Warn client about 
the need for long ­term antibiotics and the 
likelihood of residual degenerative joint disease.
• Acute disease with minimal radiographic 
changes—joint drainage and lavage via 
needle arthrocentesis, arthroscopic lavage, Arthritis, Septic

Canine and Feline, Seventh Edition  119
A
or arthrotomy; an irrigation catheter 
(ingress/egress) can be placed in larger 
joints. • Chronic disease—may require 
open arthrotomy with debridement of the 
synovium and copious lavage; if approp­
riate, an irrigation catheter (ingress/egress) 
may be placed to lavage the joint 
postoperatively. • Lavage—use warmed 
physiologic saline or lactated Ringer’s 
solution (2–4 mL/kg q8h) until effluent is 
clear; do not add povidone/iodine or 
chlorhexidine to lavage fluid. • Effluent 
fluid—cytologically monitored daily for 
existence and character of bacteria and 
neutrophils. • Removal of catheters—when 
effluent fluid has no bacteria and the 
neutrophils are cytologically healthy. 
• Arthroscopy allows for visual assessment 
of articular cartilage, lavage, and biopsy, and 
is a less invasive method of thorough joint 
lavage than arthrotomy. • Recent reports 
suggest there may be no difference between 
combined medical and surgical management 
and medical management alone.
• Pending culture susceptibility data—
bactericidal antibiotics, such as first ­generation 
cephalosporin or amoxicillin–clavulanic acid, 
preferred. • Choice of antimicrobial drugs—
primarily depends on in vitro determination 
of susceptibility of microorganisms; toxicity, 
frequency, route of administration, and 
expense also considered; most penetrate the 
synovium well; need to be given for a 
minimum of 4–8 weeks. • Nonsteroidal 
anti­inflammatory drugs (NSAIDs)—may 
help decrease pain and inflammation.
Avoid fluorinated quinolones in pediatric 
patients, as their use has induced cartilage 
lesions experimentally.
Failure to respond to conventional antibiotic 
therapy—may indicate anaerobic disease, 
other unusual cause (fungal, spirochete), or 
aseptic arthritides.
N/A
• If drainage and irrigation catheters have 
been placed—may be removed after 4–6 days 
or after reassessment of synovial fluid cytology. 
• Duration of antibiotic therapy—2 weeks 
following resolution of clinical signs; total 
treatment may be 4–8 weeks or longer, 
depending on clinical signs and pathogenic 
organism. • Persistent synovial inflammation 
without viable bacterial organisms (dogs)—
may be caused by antigenic bacterial fragments 
or antigen antibody deposition. • Systemic 
corticosteroid therapy (after joint sepsis has 
been resolved) and aggressive physical 
therapy—may be needed to maximize normal 
joint dynamics.
If clinical signs recur, early (within 24–48 
hours) treatment provides the greatest 
benefit.
• Chronic disease—severe degenerative joint 
disease. • Recurrence of infection. • Limited 
range of joint motion. • Generalized sepsis. 
• Osteomyelitis.
• Acutely diagnosed disease (within 24–48 
hours) responds well to antibiotic therapy. 
• Delayed diagnosis or resistant or highly 
virulent organisms—guarded to poor 
N/A
N/A
N/A
N/A
SYNONYMS
• Infectious arthritis. • Joint ill.
SEE ALSO
• Polyarthritis, Erosive, Immune ­Mediated.ABBREVIATIONS
drug.
Benzioni H, Shahar R, Yudelevitch S, Milgram J. 
Bacterial infective arthritis of the coxofemo­
ral joint in dogs with hip dysplasia. Vet 
Comp Orthop T raumatol 2008, 
21:262–266.
Clements DN, Owen MR, Mosely JR, et al. 
Retrospective study of bacterial infective 
arthritis in 31 dogs. J Small Anim Pract 
2005, 46:171–176.
Ellison RS. The cytologic examination of 
synovial fluid. Semin Vet Med Surg Small 
Anim 1988, 3:133–139.
Fitch RB, Hogan TC, Kudnig ST. Hematogenous 
septic arthritis in the dog: results of five 
patients treated nonsurgically with 
antibiotics. J Am Anim Hosp Assoc 2003, 
39:563–566.
Luther JF , Cook JL, Stoll MR. Arthroscopic 
exploration and biopsy for diagnosis of 
septic arthritis and osteomyelitis of the 
coxofemoral joint in a dog. Vet Comp 
Orthop T raumatol 2005, 18:47–51.
Machevsky AM, Read RA. Bacterial septic 
arthritis in 19 dogs. Aust Vet J 1999, 
77:233–237.
MacWilliams PS, Friedrichs KR. Laboratory 
evaluation and interpretation of synovial 
fluid. Vet Clin Small Anim 2003, 
33:153–178.
Mielko B, Comerford E, English K, et al. 
Spontaneous septic arthritis of canine 
elbows: twenty ­one cases. Vet Comp 
Orthop T raumatol 2018, 31:488–493.
Montgomery RD, Long IR, Milton JL. 
Comparison of aerobic culturette, synovial 
membrane biopsy, and blood culture 
medium in detection of canine bacterial 
arthritis. Vet Surg 1989, 18:300–303.
Scharf VF , Lewis ST, Wellehan JF , et al. 
Retrospective evaluation of the efficacy of 
isolating bacteria from synovial fluid in dogs 
with suspected septic arthritis. Aust Vet J 
2015, 93:200–203.
Author  Sherisse A. Sakals
available online(continued)  Arthritis, Septic

120  Blackwell’s Five-Minute Veterinary Consult  
A
  BASICS
The escape of fluid, either transudate or 
exudate, into the abdominal cavity between 
the parietal and visceral peritoneum.
• Ascites can be caused by the following:
◦ Congestive heart failure (CHF) and 
associated interference in venous return.
◦ Depletion of plasma proteins associated 
with inappropriate loss of protein from 
renal or gastrointestinal disease—protein-
losing nephropathy or enteropathy, 
◦ Obstruction of the vena cava or portal 
vein, or lymphatic drainage due to 
neoplastic occlusion.
◦ Overt neoplastic effusion.
◦ Peritonitis—infective or inflammatory.
◦ Electrolyte imbalance, especially 
hypernatremia.
◦ Liver cirrhosis.
• No species or breed predisposition.
SIGNS
• Episodic weakness.
• Abdominal fullness.
• Abdominal discomfort when palpated.
• Dyspnea from abdominal distension or 
associated pleural effusion.
• Weight gain.
• Scrotal or preputial edema.
• Groaning when lying down.
CAUSES
• Nephrotic syndrome.
• Cirrhosis of liver.
• Right-sided CHF .
• Hypoproteinemia.
• Ruptured bladder.
• Peritonitis.
• Abdominal neoplasia.
• Abdominal hemorrhage.
N/A  DIAGNOSIS
Differentiating Abdominal Distension 
without Effusion
• Organomegaly—hepatomegaly,  splenomegaly,  
renomegaly, and hydrometra.
• Pregnancy.
• Bladder distension.
• Obesity.
• Gastric dilatation.
Differentiating Diseases
• T ransudate—nephrotic syndrome, cirrhosis 
of liver, right-sided CHF , hypoproteinemia, 
and ruptured bladder.
• Exudate—peritonitis, abdominal neoplasia, 
and hemorrhage.
• Neutrophilic leukocytosis occurs in patients 
with systemic infection.
• Albumin is low in patients with impaired 
liver synthesis, gastrointestinal loss, or renal 
loss.
• Cholesterol is low in patients with impaired 
liver synthesis.
Liver Enzymes
• Low to normal in patients with impaired 
• High in patients with liver inflammation, 
hyperadrenocorticism, gallbladder obstruc-
tion, and chronic passive congestion.
Total and Direct Bilirubin
• High in patients with biliary obstruction 
caused by tumor, gallbladder distension, or 
Blood Urea Nitrogen (BUN) 
and Creatinine
• High in patients with renal failure.
• BUN low in patients with impaired liver 
synthesis or hyperadrenocorticism.
Glucose
Low in patients with impaired liver 
synthesis.
• To detect hypoproteinemia—protein 
electrophoresis and immune profile.
• To detect proteinuria—urinary protein : 
creatinine ratio (normal <0.5 : 1).
• To detect liver ascites—analysis of serum 
ascites albumin gradient.
IMAGING
• Thoracic and abdominal radiography is 
sometimes helpful.• Ultrasonography of the liver, spleen, 
pancreas, kidney, bladder, and abdomen can 
often determine cause.
• Stages of ascites:
◦ Stage I—minimal ascites: detected by 
ultrasound only.
◦ Stage II—moderate ascites: abdominal 
distention visible and/or noted on 
ballottement.
◦ Stage III—significant ascites: marked 
abdominal distention; patient uncomfort-
able, possibly with labored breathing.
Ascitic Fluid Evaluation
Exfoliative cytologic examination and 
bacterial culture and antibiotic sensitivity—
remove approximately 3–5 mL of abdominal 
fluid via aseptic technique.
Transudate
• Clear and colorless.
• Protein <2.5 g/dL.
• Specific gravity <1.018.
• Cells <1,000/mm3—neutrophils and 
mesothelial cells.
Modified Transudate
• Red or pink; may be slightly cloudy.
• Protein 2.5–5 g/dL.
• Specific gravity >1.018.
• Cells <5,000/mm3—neutrophils,  mesothelial 
cells, erythrocytes, and lymphocytes.
Exudate (Nonseptic)
• Pink or white; cloudy.
• Cells 5,000–50,000/mm3—neutrophils, 
mesothelial cells, macrophages, erythrocytes, 
and lymphocytes.
Exudate (Septic)
• Red, white, or yellow; cloudy.
• Protein >4.0 g/dL.
• Cells 5,000–100,000/mm3—neutrophils, 
lymphocytes, and bacteria.
Hemorrhage
• Red; spun supernatant clear and sediment 
red.
• Protein >5.5 g/dL.
• Specific gravity 1.007–1.027.
• Cells consistent with peripheral blood.
• Does not clot.
Chyle
• Pink, straw, or white.
• Protein 2.5–7 g/dL.
• Specific gravity 1.007–1.040 and above.
• Cells <10,000/mm3—neutrophils, 
mesothelial cells, and large population of 
small lymphocytes.Ascites

Canine and Feline, Seventh Edition  121
A
• Other—fluid in tube separates into 
cream-like layer when refrigerated; fat 
droplets stain with Sudan III.
Pseudochyle
• White.
• Protein >2.5 g/dL.
• Specific gravity 1.007–1.040.
• Cells <10,000/mm3—neutrophils, meso  - 
thelial cells, and small lymphocytes.
• Other—fluid in tube does not separate into 
cream-like layer when refrigerated; does not 
stain with Sudan III.
Urine
• Clear to pale yellow.
• Specific gravity 1–1.040 and above.
erythrocytes, lymphocytes, and macrophages.
• Other—if the urinary bladder ruptured 
<12 hours before, urinary glucose and protein 
could be negative; if bladder ruptured >12 
hours before, urine becomes a dialysis 
medium with ultrafiltrate of plasma, and 
urine contains glucose and protein.
Bile
• Slightly cloudy and yellow.
• Cells 5,000–750,000/mm3—neutrophils, 
erythrocytes, macrophages, and lymphocytes.
• Other—bilirubin confirmed by urine 
dipstick; nonicteric patient may have gall- 
bladder rupture, biliary tree leakage, or 
rupture in the proximal bowel.
  TREATMENT
• Can design treatment on an outpatient basis, 
with follow-up or inpatient care, depending on 
physical condition and underlying cause.
• If patients are markedly uncomfortable 
when lying down or become more dyspneic 
with stress, consider removing enough ascites 
to reverse these signs.
• Dietary salt restriction may help control 
transudate fluid accumulation due to CHF , 
cirrhosis, or hypoproteinemia.
• For exudate ascites control, address the 
underlying cause; corrective surgery is often 
indicated, followed by specific therapeutic 
management (e.g., patient with splenic 
tumor: tumor removed, abdominal 
bleeding controlled, blood transfusion 
administered).Large-Volume Paracentesis
• Stage III treatment.
• Pretreat patient with hetastarch (6%) 
@ 1–2 mL/kg for 2 hours.
• Abdominal tap (paracentesis), until 
drainage slows.
• Post-treat patient with hetastarch (6%) 
@ 1–2 mL/kg for 4 hours.
• Patients with liver insufficiency or CHF—
restrict sodium and give a diuretic combination 
of furosemide (1–2 mg/kg q8h PO) and 
spironolactone (1–2 mg/kg q12h PO); if control 
is inadequate, hydrochlorothiazide (1–4 mg/kg 
q12h PO) can be added ( cautiously ); must 
monitor serum potassium concentration to 
prevent potassium imbalances.
• Additionally for patients in CHF—
pimobendan (0.3 mg/kg q12h PO) and an 
angiotensin-converting-enzyme inhibitor 
(e.g., enalapril 0.25-0.5 mg/kg q12h PO).
• Patients with hypoproteinemia, nephrotic 
syndrome, and associated ascitic fluid 
accumulation—can treat as above with the 
addition of hetastarch (6% hetastarch in 
0.9% NaCl); administer an IV bolus (dogs, 
20 mL/kg; cats, 10–15 mL/kg) slowly over ~1 
hour; hetastarch increases plasma oncotic 
pressure and pulls fluid into the intravascular 
space for up to 24–48 hours.
• Systemic antibiotic therapy is dictated by 
bacterial identification and sensitivity testing 
in patients with septic exudate ascites.
  FOLLOW-UP
• Varies with the underlying cause.
• Check sodium, potassium, BUN, creati-
nine, and weight fluctuations periodically if 
the patient is maintained on a diuretic.
Aggressive diuretic administration may 
cause hypokalemia, which could predispose 
to metabolic alkalosis and exacerbation of 
hepatic encephalopathy in patients with 
underlying liver disease; alkalosis causes a 
shift from ammonium (NH4) to ammonia 
(NH3).  MISCELLANEOUS
N/A
N/A
SYNONYMS
Abdominal effusion.
SEE ALSO
• Cirrhosis and Fibrosis of the Liver.
• Congestive Heart Failure, Right-Sided.
• Hypoalbuminema.
• Nephrotic Syndrome.
Gompf RE. The history and physical examina -
tion. In: Smith FWK, Tilley LP , Oyama MA, 
Sleeper MM, eds., Manual of Canine and 
Feline Cardiology, 5th ed. St. Louis, MO: 
Saunders Elsevier, 2016, pp. 3–24.
Kramer RE, Sokol RJ, Yerushalmi B, et al. 
Large-volume paracentesis in the management 
of ascites in children. J Ped Gastro Nutr 
2001; 33:245–249.
Kumar KS, Srikala D. Ascites with right 
heart failure in a dog: diagnosis and manage -
ment. J Adv Vet Anim Res 2014, 
1(3):140–144.
Lewis LD, Morris ML Jr, Hand MS. Small 
Animal Clinical Nutrition, 3rd ed. Topeka, 
KS: Mark Morris Associates, 1987.
Li MK. Management of ascites. Hong Kong 
Med Di 2009; 14:27–29.
Pradham MS, Dakshinkar NP , Waghaye UG, 
Bodkhe AM. Successful treatment of ascites 
of hepatic origin in dog. Vet World 2008; 
1(1):23.
Runyon BA. Management of adult patients 
with ascites due to cirrhosis. Hepatol 2004; 
39:1–16.
Saravanan M, Sharma K, Kumar M, et al. 
Analysis of serum ascites albumin gradient 
test in ascitic dogs. Vet World 2012, 
5(5):285–287.
Author  Jerry A. Thornhill
available online(continued)  Ascites

122  Blackwell’s Five-Minute Veterinary Consult  
A
  BASICS
OVERVIEW
• Opportunistic fungal infection caused by 
Aspergillus  spp., common molds that are 
ubiquitous in the environment, forming 
spores in dust, straw, grass clippings, hay.
• Disseminated disease does not appear to be 
related to nasal form of disease.
• Disseminated disease—usually A. terreus  or 
A. deflectus , but other Aspergillus  species have 
also been described; A. fumigatus  causes nasal 
or pulmonary disease; typically does not 
disseminate.
• Portal of entry not definitively established, 
possibly through respiratory tract or gastro  - 
intestinal tract, with subsequent hematog-
enous spread.
• Most commonly affects intervertebral 
discs, bones, thoracic lymph nodes, lung, 
renal pelvis; localized respiratory (broncho-  
pulmonary aspergillosis) or, rarely, cornea or 
ear canal disease can occur, often with 
Aspergillus  species other than A. terreus  or A. 
deflectus .
• Sinoorbital aspergillosis has been described 
in cats; may be caused by variety of species 
including Aspergillus felis .
Dogs
• Considerably more common in dogs than 
in cats.
• German shepherd dogs, and less so 
Rhodesian ridgebacks, overrepresented, but 
reported sporadically in many breeds; average 
age 3 years (range 2–8 years); females three 
times more likely to develop disease than males.
Cats
• Persians—overrepresented for sinoorbital 
aspergillosis.
• Disseminated cases mostly affect lungs and/
or gastrointestinal tract.
SIGNS
Dogs
• May develop acutely or slowly over a period 
of several months.
• Lameness—fungal osteomyelitis, with focal 
pain and swelling.
• Neurologic—fungal discospondylitis 
causing paraparesis, paraplegia, spinal pain; 
central signs—vestibular signs, circling, 
seizures, hemiparesis, mental dullness, ataxia, 
vision impairment.
• Renal involvement—polyuria/polydipsia, 
vomiting, inappetence, weight loss.
• Respiratory—cough, increased respiratory 
effort, decreased lung sounds due to pleural 
effusion.
• Cardiac—arrhythmias.
• Gastrointestinal—abdominal distension, 
anorexia, vomiting, diarrhea.• Ocular—uveitis, chorioretinitis, hyphema, 
panophthalmitis.
• Nonspecific—fever, weight loss, weakness, 
vomiting, lymphadenopathy.
Cats
• Usually nonspecific signs (e.g., lethargy, 
vomiting, and diarrhea).
• Ocular—exophthalmos.
• Caused by Aspergillus  species, most commonly 
A. terreus or A. deflectus , but other species have 
also been described (e.g., A. niger , A. flavipes , A. 
versicolor , A. lentulus , A. alabamensis ).
• A. felis  recently reported to cause fungal 
rhinosinusitis in cats, sinoorbital aspergillosis 
in cats, disseminated disease in dogs, 
pulmonary aspergillosis in humans.
• German shepherd dogs, purebred dogs, 
immunosuppressed animals at higher risk.
• Geographic/environmental conditions—may 
be factor, as some regions have higher incidence 
(e.g., California, Louisiana, Michigan, Georgia, 
Florida, Virginia in the United States; Western 
Australia; Barcelona; Milan).
• Cats—described in association with feline 
infectious peritonitis (FIP), feline panleuko-
penia virus, feline leukemia virus (FeLV), 
diabetes mellitus, chemotherapy.
  DIAGNOSIS
• Bacterial osteomyelitis/discospondylitis.
• Spinal neoplasia.
• Intervertebral disc disease.
• Skeletal neoplasia.
• Bacterial pyelonephritis.
• Bacterial pneumonia.
• Other causes of vestibular abnormalities or 
seizures.
• Other causes of uveitis (see Anterior 
Uveitis—Cats; Anterior Uveitis—Dogs).
• Nonspecific.
• CBC:
◦ Dogs—mature neutrophilic leukocytosis, 
sometimes with eosinophilia and monocyto -
sis; one-third have normocytic, normo -
chromic, nonregenerative anemia.
◦ Cats—may have nonregenerative anemia, 
leukopenia.
• Biochemistry—variable hyperglobulinemia, 
increases in activity of alkaline phosphatase 
(ALP), alanine aminotransferase (ALT), and 
amylase; increased concentrations of serum, 
creatinine, phosphate, blood urea nitrogen 
(BUN), and calcium.
• Urinalysis—possible isosthenuria, microscopic 
hematuria, pyuria, fungal hyphae in sediment.
• Methods of detection include cytology, 
culture, histopathology.• Definitive diagnosis by fungal culture from 
normally sterile body fluids and tissues (urine, 
bone, cerebrospinal fluid (CSF), blood, lymph 
node, pleural effusions, intervertebral disc 
aspirates, kidney, spleen); urine culture 
positive in 50% of dogs.
• Culture on Sabouraud’s dextrose agar 
(requires 5–7 days).
• Antibody serology is highly insensitive for 
diagnosis of disseminated aspergillosis.
• Galactomannan antigen ELISA (urine or 
serum)—good sensitivity (89%) and 
specificity (89%); pulmonary and ocular 
infections have lower sensitivity; false positive 
in dogs treated with Plasmalyte or with other 
mycotic infections ( Penicillium , Paecilomyces , 
Cladosporidium , Geotrichum , Histoplasma , 
Cryptococcus ).
• Cats—test for FeLV and feline immuno -
IMAGING
Radiographic Findings
• Spinal views may show end-plate lysis, 
productive lesions with bridging spondylosis, 
lysis of vertebral bodies.
• Bony proliferation, lysis, periosteal reaction 
typical of osteomyelitis of diaphyseal region 
of long bones.
• Pulmonary involvement rare; mixed interstitial/  
alveolar pattern, enlarged sternal and/or 
tracheobronchial lymph nodes, pleural 
effusion; productive and destructive lesions of 
sternebrae; cavitary pulmonary lesions in dogs 
with chronic pulmonary localization.
Ultrasonographic Findings
• Kidneys—most common site to detect 
changes; renal pelvis dilation ± echogenic 
debris within pelvis, loss of corticomedullary 
distinction, renal distortion with mottled 
appearance of parenchyma, dilation of 
proximal ureter, renomegaly, nodules or 
masses, hydronephrosis.
• Spleen—hypoechoic, lacy, sharply demar -
cated areas with no Doppler signal (suggestive 
of infarct), nodules/masses, mottled paren -
chyma, splenic venous thrombosis.
• Other—abdominal lymphadenomegaly, 
diffuse hepatic hypoechogenicity, ascites, or 
evidence of venous thrombosis.
MRI Findings
Useful for further defining brain lesions in 
animals with CNS abnormalities; changes 
similar to other infectious and noninfectious 
inflammatory brain diseases; may identify 
subtle vertebral lesions in dogs with disco  - 
spondylitis.
Area to collect sample relies on clinical 
presentation, but may include CSF tap, 
intervertebral disc space aspirates, abdomino -
centesis/thoracocentesis, aspirate of various 
organs (spleen, liver, kidney) or lymph nodes.Aspergillosis, Disseminated Invasive

Canine and Feline, Seventh Edition  123
A
• Hyphae that branch at 45-degree angle; 
special stains assist organism detection.
• Focal osteomyelitis with multiple pale 
granulomas in kidneys, spleen, lymph node, 
myocardium, pancreas, liver.
• Pyogranulomatous inflammation can be 
found in lungs, eyes, thyroid, uterus, brain, 
prostate; contain numbers of septate, branch  - 
ing hyphae that may have characteristic 
lateral branching aleuriospores ( A. terreus ).
• Best visualized with periodic acid-Schiff, 
Gomori’s methenamine silver, or Crocott’s stain.
  TREATMENT
DOGS
• T reatment rarely curative; may result in 
partial clinical remission or halt progression 
of clinical signs; severely ill dogs have poor 
• Fluid therapy—indicated by volume status, 
degree of renal compromise.
• Pulmonary lobectomy followed by systemic 
antifungals has been successful in dogs with 
cavitary lesions without evidence of dissem  - 
ination.
CATS
Disseminated—likely difficult to treat; 
limited data.
• Combination itraconazole (5–10 mg/kg 
PO q24h or divided q12h) and amphotericin B (dogs, 2–3 mg/kg IV 
3 days/week for 9–12 treatments, to 
cumulative dose of 24–27 mg/kg)—treatment 
of choice.
• Itraconazole monotherapy has achieved 
remission for months to 1–2 years in small 
number of dogs.
• New triazoles—voriconazole and 
posaconazole both have activity against 
Aspergillus ; some dogs treated with them have 
gone into remission for many months; 
Aspergillus  spp. and other molds are 
intrinsically resistant to fluconazole, so it 
should not be used.
• Terbinifine (5–10 mg/kg PO q24h) alone 
or in combination with triazoles has been 
used to treat resistant infections, with unclear 
benefit.
• β-glucan synthase inhibitors caspofungin, 
micafungin, anidulafungin—limited clinical 
information in dogs, but efficacious in 
invasive aspergillosis in humans.
• Amphotericin B—contraindicated in dogs 
with preexisting renal compromise or failure; 
amphotericin B lipid complex reduces likeli  - 
hood of nephrotoxicity.
• Oral azoles—nausea, intermittent anorexia, 
liver enzyme elevation.
• Avoid midazolam and cisapride with 
azoles—fatal drug reactions noted in 
humans.
• Hepatotoxicity and ulcerative dermatitis 
more likely to occur at doses of itraconazole 
≥10 mg/kg/day; discontinue itraconazole if 
adverse effects occur; may be able to reinstitute 
at lower dose once side effects have resolved.  FOLLOW-UP
• Disseminated—monitor serial radiographs 
every 1–2 months, renal function, and urine 
cultures.
• Prognosis poor, especially in purebred dogs 
that lack other reasons for immune compromise.
None
• ALT = alanine transaminase.
Maddison JE, Page SW, Church DB. Small 
Animal Clinical Pharmacology, 2nd ed. 
Edinburgh: Saunders, 2008, pp. 186–197.
Sykes, JE. Canine and Feline Infectious 
Diseases. Philadelphia, PA: Saunders, 2014, 
pp. 639–647.
Author  Jane E. Sykes
Hannah N. Pipe-Martin and Stephen C. Barr.
available online(continued)  Aspergillosis, Disseminated Invasive

124  Blackwell’s Five-Minute Veterinary Consult  
A
  BASICS
Nasal fungal disease caused by opportunistic 
ubiquitous saprophytic fungi that are members 
of the Aspergillus fumigatus  species complex.
• Inhalation of fungus leads to disease in the 
nasal cavity with destruction of turbinates, 
formation of plaque lesions, and 
overproduction of mucus, causing clinical 
signs of nasal disease; does not result in 
systemic mycosis.
• In dogs, confined to nasal cavity and frontal 
sinus—sinonasal form.
• In cats, can result in sinonasal or sino-
orbital disease.
• Respiratory—sinonasal form in dogs and cats.
• Ophthalmic—sino-orbital form in cats.
GENETICS
Unknown
Unknown, but a common diagnosis in dogs 
with nasal discharge in many locations.
Worldwide
Species
Dogs and cats (less common).
• Dogs—dolichocephalic and mesocephalic 
breeds.
• Cats—brachycephalic breeds may be 
Predominantly young to middle-aged.
None identified.
SIGNS
• Unilateral or bilateral nasal discharge—
typically mucoid, mucopurulent, or 
serosanguinous; may be primarily epistaxis.
• Sneezing.
• Typically chronic signs—several months.
• Many patients will have been treated with 
antibiotics for a possible bacterial infection, 
with variable response.
• Unilateral or bilateral nasal discharge.
• Typically increased nasal airflow on the 
affected side.
• Depigmentation with ulceration of the 
nasal planum.
• Facial pain.
• Ipsilateral mandibular lymphadenopathy.• Sino-orbital disease in cats—stertor, exoph  - 
thalmos, exposure keratitis, hard palate 
ulceration, facial asymmetry, loss of nasal airflow.
CAUSES
• No underlying cause identified, although 
preexisting foreign body or trauma is 
occasionally implicated.
• Likely due to inhalation of a large bolus 
of fungus from the environment, most 
commonly from the Aspergillus fumigatus  
species complex— A. fumigatus  in sinonasal 
disease, A. felis  in sino-orbital disease.
Unknown
  DIAGNOSIS
• Oronasal fistula.
• Lymphoplasmacytic rhinitis.
• Nasopharyngeal polyp or 
cryptococcosis—cats.
• Often normal.
• Possible inflammatory leukogram.
Serology
• Detects fungi-specific serum antibodies.
• Agar gel immunodiffusion (AGID)—
commercially available; 98% specificity, 67% 
sensitivity in dogs; 43% sensitivity in cats. 
Serial serology does not appear to correlate 
with clinical status.
• ELISA—88% sensitivity, 97% specificity in 
dogs; 90% sensitivity in cats.
• Counter-immunoelectrophoresis—85% 
specificity in dogs.
• Serum galactomannan—unreliable.
Culture
• Tissue fungal culture—visualized biopsy 
sample taken from a region of suspected 
fungal growth showed 100% specificity, 81% 
sensitivity in dogs.
• Culture of nasal discharge is less sensitive 
and specific.
IMAGING
CT
• Imaging method of choice.
• Allows for evaluation of the cribriform plate.
• Cavitated turbinate lysis, thickening of the 
mucosa along the nasal turbinates.
• Frontal sinus proliferative mass effect.
• Cats—soft tissue mass in the choana or 
nasopharynx.
Skull Radiography
• Intraoral dorsoventral radiograph of the 
nasal cavity shows turbinate lysis.• Rostrocaudal or skyline frontal sinus view 
may show increased soft tissue density in the 
frontal sinus.
• Cannot evaluate cribriform.
Rhinoscopy
• Allows for visualization of fungal plaques 
(white, yellow, black, or light green) on the 
mucosa of the nasal cavity and/or frontal sinus.
• Rigid rhinoscopy—examination of the 
nasal cavity alone; good visualization is 
possible due to large airspaces caused by 
turbinate lysis; excessive mucus and bleeding 
can make full examination difficult.
• Flexible rhinoscopy in dogs allows exam- 
ination of the nasopharynx and frontal sinus 
if the opening of the nasofrontal duct is 
destroyed by fungal infection.
• Sinuscopy—may be required to confirm the 
diagnosis in dogs that lack nasal cavity plaques.
• Biopsies obtained of affected area under 
direct rhinoscopic visualization using cup 
biopsy instruments.
• Samples placed in formalin, routinely 
processed.
• Identification of septate, branching hyphae, 
and conidia on histopathology with 
surrounding inflammation.
• Blind biopsies in an unaffected area of the 
nasal cavity can result in a false diagnosis of 
inflammation.
  TREATMENT
Overnight hospitalization advised after 
topical treatment or surgery.
Maintain the nares free of nasal discharge.
ACTIVITY
Restriction of activity is not required if no 
bleeding is documented.
DIET
N/A
• Dogs—inform client that multiple topical 
treatments may be necessary for cure.
• No established protocols for treatment in cats.
Endoscopic Debridement
Extensive curettage and removal of fungal 
material from the nose and frontal sinus are 
essential for efficacy of topical medication.
Trephination of the Frontal Sinus
• May be required for dogs with frontal sinus 
involvement where access cannot be established 
via rhinoscopy.Aspergillosis, Nasal

Canine and Feline, Seventh Edition  125
A
• Performed using a Jacob’s chuck and 
intramedullary pin.
Surgical Debridement and/or 
Exenteration
• Rhinotomy for debridement in some dogs.
• Exenteration in some cats with sino-orbital 
disease.
• Clotrimazole and enilconazole are the most 
widely used drugs topically in different 
formulations and protocols.
• T reatment is usually performed during the 
same anesthesia as diagnostics, after debride- 
ment.
• No consensus regarding the most effective 
therapy; three protocols are described here.
Clotrimazole Solution Infusion
• Clotrimazole solution 1% infused through 
catheters placed into the nasal cavity and 
frontal sinus via trephination, or in the nasal 
cavity only; reported efficacy of up to 87% in 
dogs with multiple treatments.
• Has been used in cats with sinonasal disease 
with varying success.
Combined Clotrimazole Irrigation 
and Depot Therapy
Frontal sinus trephination with flushing of 
1% clotrimazole solution followed by 1% 
clotrimazole cream instilled as a depot agent; 
reported efficacy of 86% with multiple 
treatments needed in one dog.
Debridement and Clotrimazole Depot 
Therapy under Rhinoscopic Guidance
Debridement and sinus and nasal depot 
therapy with 1% clotrimazole cream under 
rhinoscopic guidance; reported efficacy of 
100% with multiple treatments.
Systemic Therapy
• Antifungal triazole drugs should be 
considered if the cribriform is not intact; can 
also be combined with topical therapy.
• Used as primary therapy in some cats.
• May be cost-prohibitive.
• Itraconazole 5 mg/kg PO q12h in dogs; 
reported efficacy of 60–70%; 10 mg/kg PO 
q24h in cats.
• Posaconazole 5 mg/kg PO q12h with 
terbinafine 30 mg/kg PO q12h and doxycycline 5 mg/kg PO q12h for refractory 
disease; complete remission reported in 
7/10 dogs, partial clinical remission in 3/10 
dogs; 2/10 dogs relapsed after cessation of 
therapy.
• Voriconazole 5 mg/kg PO q12h in dogs; 
efficacy has not been established; neurotoxic 
in cats.
• Fluconazole is not recommended due to 
resistance.
• A breach in the cribriform plate was 
thought to be a contraindication to topical 
treatment; two recent retrospective studies 
showed no adverse neurologic effects after 
topical treatment in dogs with lysis of the 
cribriform and/or frontal sinus floor.
• Sino-orbital disease in cats necessitates the 
use of systemic therapy.
Topical clotrimazole and enilconazole are 
caustic to mucosal surfaces; all staff in close 
contact should wear protective gear.
Homeopathic remedy—aurum metallicum 
reported to have resulted in a resolution of 
clinical signs and clearance of organisms in a 
dog unresponsive to topical therapy.
  FOLLOW-UP
Dogs
• Reduction of clinical signs does not 
establish resolution of disease.
• Follow-up rhinoscopy with possible 
histopathology and culture is recommended 
to establish a response to treatment.
• Serial serology (AGID) appears not to 
correlate with disease status.
• Repeat CT should be considered for 
reassessment of the cribriform plate before 
repeat topical treatment if worsening clinical 
signs are seen.
Dogs and Cats
• Monitor liver enzymes on triazole therapy.
• Monitor renal parameters on amphotericin B.
N/APOSSIBLE COMPLICATIONS
• Topical therapy—monitor for any complica  - 
tions such as swelling of oropharynx, 
neurologic signs, infection/swelling of trephine 
site.
• T riazoles can cause anorexia and can be 
hepatotoxic.
• Amphotericin B can be nephrotoxic.
• The prognosis in dogs is good, though 
multiple topical treatments may be needed; 
recurrence or reinfection can occur years after 
supposedly successful therapy.
• The prognosis for cats with sinonasal 
disease is better than with the sino-orbital 
form.
N/A
No documented cases of human infection 
from an affected dog or cat.
N/A
• AGID = agar gel immunodiffusion.
Barrs VR, Talbot JJ. Feline aspergillosis. Vet 
Clin North Am 2014, 44(1):51–73.
Friend E, Anderson DM, White RAS. 
Combined clotrimazole irrigation and depot 
therapy for canine nasal aspergillosis. J 
Small Anim Pract 2006, 47(6):312–315.
Mathews KG, Davidson AP , Koblik PD, et al. 
Comparison of topical administration of 
clotrimazole through surgically placed 
versus nonsurgically placed catheters for 
treatment of nasal aspergillosis in dogs: 
60 cases (1990–1996). J Am Vet Med Assoc 
1998, 213:501–506.
Sharman M, Mansfield CS. Sinonasal 
aspergillosis in dogs: a review. J Small Anim 
Pract 2012, 53:434–444.
Vedrine B, Fribourg-Blanc L-A. T reatment of 
sinonasal aspergillosis by debridement and 
sinonasal deposition therapy with clotrimazole 
under rhinoscopic guidance. J Am Anim 
Hosp Assoc 2018, 54:103–110.
Author  Jill S. Pomrantz
Consulting Editor  Elizabeth Rozanski(continued)  Aspergillosis, Nasal

126  Blackwell’s Five-Minute Veterinary Consult  
A
  BASICS
OVERVIEW
• Given for its antipyretic, analgesic, anti- 
inflammatory, and antiplatelet effects.
• Aspirin inhibits cyclooxygenase, reducing the 
synthesis of prostaglandins and thromboxanes.
• Gastric irritation and hemorrhage can occur.
• Repeated doses can produce gastrointestinal 
ulceration and perforation and hepatic injury; 
renal injury is uncommon.
• Toxic hepatitis, marked metabolic acidosis, 
and anemia can occur, especially in cats (long 
half-life).
• Hepatic damage may not be dose related.
Cats and less commonly dogs.
SIGNS
• Depression, lethargy.
• Vomiting ± blood.
• Diarrhea ± blood; melena.
• Pallor.
• Polyuria/polydipsia (rare).
• Muscular weakness and ataxia.
• Ataxia, coma, seizures, and death in 1 or 
more days.
• Owners employing human dosage guide- 
lines to medicate cats and dogs.
• Dogs—single 25 mg/kg dose has resulted in 
gastric bleeding.
• Cats have a decreased ability to conjugate 
salicylate with glycine and glucuronic acid 
due to a deficiency in glucuronyl transferase.
• Half-life increases with dosage—cats, 22–27 
hours for 5–12 mg/kg and approximately 44 
hours for 25 mg/kg; responsible for higher risk 
in cats. Dogs, half-life = 7.5 hours.
• Elimination is slower in neonatal and 
geriatric patients.
• Patients with hypoalbuminemia may be at 
higher risk of toxicity because aspirin is highly 
protein bound to plasma albumin.
  DIAGNOSIS
• Ethylene glycol or alcohol.
• Anticoagulant rodenticides.
• Other causes of liver failure, including 
acetaminophen, iron, metaldehyde, and 
blue-green algae.
• Cats—prone to Heinz body formation.
• Decreased packed cell volume (PCV); may 
be marked, especially in cats.• Leukocytosis.
• Elevated liver enzymes.
• Elevated renal values (rare).
• Initial respiratory alkalosis followed by 
marked metabolic acidosis.
• High ketones and pyruvic, lactic, and 
amino acid levels.
• Decreased sulfuric and phosphoric acid 
renal clearance.
IMAGING
• Abdominal imaging (perforation).
• Salicylic acid concentrations in serum.
  TREATMENT
• Inpatient—following general principles of 
poisoning management.
• Induced gastric emptying—gastric lavage or 
induced emesis.
• Correction of acid-base balance—continuous 
IV fluids; assisted ventilation and supplemental 
oxygen for severely affected animals.
• Whole blood transfusions for severe cases of 
hemorrhage and hypotension.
• Peritoneal dialysis and hemodialysis are 
advanced procedures that will increase 
salicylate clearance in severe cases.
• No specific antidote available.
• Activated charcoal—1–2 g/kg PO with a 
cathartic (sorbitol); monitor sodium 
• 5% dextrose IV to correct dehydration.
• Gastrointestinal protectants—sucralfate and 
an H2 blocker or proton pump inhibitor; 
misoprostol for patients at higher risk for 
• Sodium bicarbonate 1 mEq/kg IV in severe 
ingestions—alkalinizes urine; must closely 
monitor acid-base status.
• Diazepam 0.5–1 mg/kg IV or rectal as 
needed for seizures.
N/A
  FOLLOW-UP
• Maintaining renal function and acid-base 
balance is vital.
• Severe acid-base disturbances, severe 
dehydration, toxic hepatitis, bone marrow depression, and coma are poor prognostic 
indicators.
• Be sure that history of “aspirin” medication 
does not refer to other available pain 
• Question owner about any preexisting 
painful condition that may have prompted 
the aspirin administration.
Plumb DC. Aspirin. In: Plumb DC, ed., 
Plumb’s Veterinary Drug Handbook, 9th 
ed. Ames, IA: Wiley-Blackwell, 2018, 
pp. 92–96.
Talcott PA, Gwaltney-Brant SM. Nonsteroidal 
anti-inflammatories. In: Peterson ME, 
3rd ed. St. Louis, MO: Elsevier, 2013, 
pp. 698–700.
Consulting Editor  Lynn R. HovdaAspirin Toxicosis

Canine and Feline, Seventh Edition  127
A
  BASICS
• Chronic bronchitis—neutrophilic inflamma -
tion of the lower airways (bronchi and 
bronchioles) lacking a specific etiology; chronic 
daily cough of greater than 2 months in 
duration. • Asthma—acute or chronic airway 
inflammation associated with increased airway 
responsiveness to various stimuli, airway 
narrowing due to smooth muscle hypertrophy 
or constriction, reversibility of airway constric -
tion, and presence of eosinophils, lymphocytes, 
and mast cells within the airways. • Bronchitis 
is thought to result in airflow obstruction due to 
airway remodeling, while asthma is associated 
with airway constriction; however, clinically the 
two disease processes can appear similar. No 
physical examination findings or biomarkers can 
distinguish between the two syndromes, 
although reversal of airflow obstruction 
following administration of a beta‐agonist is 
suggestive of the asthmatic form of disease.
• Lower airway inflammation likely results from 
inhalation of irritant substances. • Bronchiolar 
smooth muscle constriction—can resolve 
spontaneously or with treatment. • Increase in 
mucosal goblet cells, mucus production, and 
edema of bronchial wall associated with 
inflammation. • Excessive mucus can cause 
bronchiolar obstruction, atelectasis, or bronchi  - 
ectasis. • Smooth muscle hypertrophy implies 
chronicity—usually not reversible. • Chronic 
inflammation leads to airway remodeling and 
irreversible airflow obstruction.
• Respiratory. • Cardiac—pulmonary hyper- 
tension rarely.
Worldwide
Species
Cat
Siamese overrepresented.
Any age; more common between 2 and 8 
years.
One study showed females overrepresented.
SIGNS
• Coughing, tachypnea, labored breathing or 
wheezing. • Signs are typically episodic and 
can be acute or chronic.
• Severely affected cats present with open‐
mouth breathing, tachypnea, and cyanosis. • Increased tracheal sensitivity is common. 
• Chest auscultation may reveal crackles and/
or expiratory wheezes, but can be normal. 
• Labored breathing with an abdominal push 
on expiration, increase in expiratory effort.
CAUSES
T riggers of airway inflammation unknown.
• Cigarette smoke, poor environmental 
hygiene, dusty cat litter, hair sprays, and air 
fresheners can exacerbate disease. • Use of 
potassium bromide—implicated in causing 
signs of bronchitis/asthma in some cats.
  DIAGNOSIS
• Rule out infectious pneumonia 
(Mycoplasma , Toxoplasma , bacterial or fungal 
pneumonia). • Consider Dirofilaria immitis  
and primary lung parasites ( Aelurostrongylus 
abstrusus , Capillaria aerophilia , Paragonimus 
kellicotti , Troglostrongylus brevior ). More 
common in southern and midwest United 
States, and in outdoor and hunting cats in 
some geographic regions. • Primary or 
metastatic neoplasia can have similar clinical 
and radiographic appearance. • Clinical 
presentation of idiopathic pulmonary fibrosis 
may appear similar to feline bronchitis.
Frequently normal; ~40% of cats with 
bronchial disease have peripheral 
eosinophilia.
• Fecal exams—flotation for Capillaria , 
sedimentation for Paragonimus , Baermann for 
Aelurostrongylus ; false‐negative results are common. 
• Heartworm antigen and antibody testing, 
particularly if coughing occurs in conjunction 
with vomiting. • Radioallergosorbent testing 
or intradermal skin testing—no correlation 
between skin allergies and respiratory disease 
currently documented.
IMAGING
• Classically, diffuse bronchial wall thicken-
ing; interstitial or patchy alveolar patterns also 
possible. • Severity of radiographic changes 
does not necessarily correlate with clinical 
severity or duration, and normal radiographs 
can be found. • Hyperinflation of lung 
fields—flattened and caudally displaced 
diaphragm, increased distance between the 
heart and diaphragm, extension of lungs to 
the first lumbar vertebrae thought to reflect 
bronchoconstriction. • Collapse of right 
middle lung lobe due to mucus plugging and 
atelectasis reported in 11% of cases. 
• Pulmonary lobar arterial enlargement is 
suspicious for heartworm disease.CT
Bronchial wall thickening, patchy alveolar 
patterns, and bronchiectasis.
Useful to document heartworm disease or 
secondary pulmonary hypertension.
Transoral Tracheal Wash (TOTW)
Use a sterile endotracheal tube and polypro-
pylene or red rubber catheter to collect airway 
fluids at the level of the carina.
Bronchoscopy
Allows visualization of trachea and bronchi. 
Excessive amounts of thick mucus are 
common with bronchitis. Mucosa of the 
airways is typically hyperemic and edematous.
Cytology of TOTW or Bronchoscopy/
Bronchoalveolar Lavage (BAL)
• Eosinophils and neutrophils are most 
prominent cell types. • Up to 20% eosino-
phils on BAL cytology can be found in 
normal cats. • A mixed inflammatory cell 
population occurs in about 21% of cats.
Bacterial Cultures
• Quantitated cultures recommended; positive 
cultures frequently encountered, but bacterial 
colony counts >100–300 cfu/mL uncommon 
with bronchitis. • Specific Mycoplasma  cultures 
and PCR for species detection.
Biopsy
Keyhole biopsy—can differentiate between 
idiopathic pulmonary fibrosis, neoplasia, and 
bronchitis if needed; rarely performed.
Hyperplasia/hypertrophy of goblet cells, 
hypertrophy of airway smooth muscle, epithelial 
erosion, and inflammatory infiltrates.
  TREATMENT
• Remove patient from environment that 
exacerbates disease. • Hospitalize for acute 
respiratory distress.
• Oxygen therapy, bronchodilators, and 
sedatives in an acute crisis. • Minimize 
manipulation in order to lessen stress and 
oxygen needs of the animal.
ACTIVITY
Usually self‐limited by patient.
DIET
Calorie restriction for obese cats.
• Most causes are chronic and progressive. 
• Do not discontinue medical therapy when 
clinical signs have resolved—subclinical 
inflammation is common and can lead to Asthma, Bronchitis—Cats

128  Blackwell’s Five-Minute Veterinary Consult  
A
progression of disease; lifelong medication 
and environmental changes usually necessary. 
• Some clients can be taught to give terbuta  - 
line subcutaneously and corticosteroid 
injections at home for a crisis situation.
Emergency Treatment
• Oxygen and a parenteral bronchodilator—
injectable terbutaline (0.01 mg/kg IV/SC); 
repeat if no clinical improvement (decrease in 
respiratory rate or effort) in 20–30 minutes. 
• A sedative can aid in decreasing anxiety 
(butorphanol tartrate at 0.2–0.4 mg/kg IV/
IM, buprenorphine at 0.01 mg/kg IV/IM, or 
acepromazine at 0.01–0.05 mg/kg SC). • A 
short‐acting parenteral corticosteroid may 
also be required—dexamethasone sodium 
phosphate (0.1–0.25 mg/kg IV/SC).
Long‐Term Management
• Decrease inflammation. • Oral treatment is 
preferred over injectable for closer monitoring 
of dose and duration. • Prednisolone—0.5–  
1 mg/kg PO q12h; begin to taper dose (50% 
each week) after 1–2 weeks if clinical signs 
have improved; maintenance therapy 
0.5–1 mg/kg PO q24–48h. • Longer‐acting 
parenteral steroids (Vetalog® or Depo‐Medrol®) 
should be reserved only for situations where 
owners are unable to administer oral or inhaled 
medication on a routine basis.
Inhaled Corticosteroids
• Requires a form‐fitting facemask, spacer, and 
metered‐dose inhaler (MDI); veterinary brand—  
Aerokat ® (T rudell Medical). • The most 
common corticosteroid used as an MDI is 
fluticasone propionate (Flovent®)—110  μg 
Flovent MDI is recommended (1–2 actuations, 
7–10 breaths q12h); in one study, use of 44  μg 
Flovent decreased BAL eosinophil counts in 
cats with experimentally induced lower airway 
disease. • Flovent is used for long‐term control 
of airway inflammation; takes 10–14 days to 
reach peak effect; use oral steroids concurrently 
during this time. • Results in some suppression 
of the hypothalamic–pituitary axis, but 
systemic side effects appear to be limited.
Bronchodilators
• Methylxanthines—sustained‐release 
theophylline formulations recommended, and 
pharmacokinetics can vary greatly; only 
compounded generic currently available; dose 
at 15–20 mg/kg PO once daily in the evening. 
• Beta‐2 agonists (terbutaline, albuterol)—
reverse smooth muscle constriction; oral 
terbutaline dose is 1/4 of a 2.5 mg tablet; 
initial albuterol dose is 1–2 puffs; avoid 
giving beta‐2 agonists daily as tachyphylaxis 
may develop.Anthelminthics
• Empirical therapy is indicated for cats with 
clinical signs of bronchial disease and 
eosinophilic airway cytology in an appropriate 
geographic location. • Consider fenbendazole, 
ivermectin, praziquantel, or milbemycin.
Use based on a positive quantitative culture and 
susceptibility testing or Mycoplasma  isolation.
Beta‐2 antagonists (e.g., propranolol) are 
contraindicated because of their ability to block 
sympathetically mediated bronchodilation.
• Long‐term use of steroids increases risk of 
development of diabetes mellitus and predisposes 
to immunosuppression. • Use of corticosteroids 
in cats may precipitate congestive heart failure. 
• Beta agonists could cause tachycardia and 
exacerbate underlying cardiac disease.
• Leukotriene receptor blockers and inhibitors of 
generation—no evidence to support use. 
• Tyrosine kinase inhibitors—masitinib is no 
longer on the market; side effects were dose 
limiting. • Antiserotonin and antihistamine 
drugs—no evidence to support use. 
• Immunotherapy—allergen‐specific rush 
immunotherapy (RIT) shows promise in treating 
asthma. • Omega 3 fatty acids/neutraceuticals—
diminished hyperresponsiveness of airway, but 
did not resolve airway eosinophilia.
  FOLLOW‐UP
• Owners should report any increase in 
coughing, sneezing, wheezing, or respiratory 
distress; medications should be increased 
appropriately, or additional therapy initiated 
if clinical signs worsen. • Follow‐up radiographs 
may be helpful to detect onset of new disease. 
• Owner should watch for signs of polyuria/
polydipsia (PU/PD) that could indicate 
diabetes mellitus or renal disease; monitor 
blood glucose and urine cultures.
Eliminate any environmental factors that can 
trigger a crisis situation (see Risk Factors); 
change furnace and air‐conditioner filters on 
a regular basis; consider dust‐free litters.
• Acute episodes can be life‐threatening. 
• Right‐sided heart disease develops rarely as 
a result of long‐term bronchitis.
• Long‐term therapy should be expected. 
• Most cats do well if recurrence of clinical 
signs is carefully monitored and medical 
therapy appropriately adjusted. • A few cats will be refractory to treatment; these carry a 
much worse prognosis.
Cor pulmonale can be a sequela to chronic 
lower airway disease.
Glucocorticoids are contraindicated in the 
pregnant animal; bronchodilators should be 
used with caution.
SYNONYMS
• Allergic bronchitis. • Asthmatic bronchitis. 
• Feline lower airway disease. • Extrinsic 
asthma. • Eosinophilic bronchitis.
SEE ALSO
• Heartworm Disease—Cats.
• Respiratory Parasites.
• BAL = bronchoscopy/bronchoalveolar lavage. 
• MDI = metered‐dose inhaler. • PU/PD = 
polyuria/polydipsia. • RIT = rush immuno -
therapy. • TOTW = transoral tracheal wash.
• www.aerokat.com • www.fritzthebrave.com
Chang C, Cohn L, DeClue A, et al. Oral 
glucocorticoids diminish the efficacy of allergen‐  
specific immunotherapy in experimental 
feline asthma. Vet J 2013, 197:268–272.
Chang DG, Dodam HR, Cohn LA, et al. An 
experimental janus kinase (JAK) inhibitor 
suppresses eosinophilic airway inflammation in 
feline asthma. ACVIM Forum Proceedings, 2013.
Cohn LA, DeClue AE, Cohen RL, Reinero CR. 
Effects of fluticasone propionate dosage in an 
experimental model of feline asthma. J Feline 
Med Surg 2010, 12(2):91–96.
Crisi P , DiCesare A, Boari A. Feline 
troglostrongylosis: current epizootiology, 
clinical features, and therapeutic pptions. Front 
Vet Sci 2018, 5:126.
Kirschvink J, Leemans J, Delvaux F , et al. Inhaled 
fluticasone reduces bronchial responsiveness 
and airway inflammation in cats with mild 
chronic bronchitis. J Feline Med Surg 2006, 
8(1):45–54.
Schulz BS, Richter P , Weber K, et al. Detection of 
feline Mycoplasma  species in cats with feline 
asthma and chronic bronchitis. J Feline Med 
Surg 2014, 16(12): 943–949.
Author  Karah Burns DeMarle
Consulting Editor  Elizabeth Rozanski
Carrie J. Miller and Lynelle R. Johnson.
available onlineAsthma, Bronchitis—Cats  (continued)

Canine and Feline, Seventh Edition  129
A
  BASICS
OVERVIEW
• Glial cell neoplasm, most commonly 
affecting the brain and rarely the spinal cord. 
• Neoplastic cells are of astrocytic origin. • The 
most common intraaxial (situated inside of the 
brain parenchyma) intracranial neoplasm of dogs, 
but is rarely diagnosed in cats. • T umors are often 
located in the pyriform area of the temporal lobe, 
the cerebral hemispheres, the thalamus, hypo  - 
thalamus, or midbrain. • Biologic behavior of 
this tumor is dictated by the histopathologic 
grade (I–IV, from best to worst prognosis) and 
anatomic involvement. • T umors typically 
do not penetrate the ventricular system or 
metastasize outside of the cranial vault.
• Dog—often brachycephalic breeds >5 years of 
age; no sex predilection reported. • Cat—usually 
>9 years; no sex or breed predilection reported.
SIGNS
• Location and growth kinetic dependent. 
• Seizures. • Behavioral changes. • Apathy 
toward normal activities, including eating, 
playing, and societal interactions. 
• Disorientation. • Loss of conscious 
proprioception. • Cranial nerve abnormal -
ities. • Head muscle atrophy. • Upper 
motor neuron tetraparesis.
  DIAGNOSIS
• Other primary tumors arising from tissues 
of the central nervous system. • Metastatic 
neoplasia with brain tropism such as hemangio  - 
sarcoma. • Granulomatous meningoencepha-
litis. • T rauma. Cerebrovascular infarction. 
• Meningitis.
Usually unremarkable.
Cerebrospinal fluid (CSF) analysis may show 
albumin-cytologic dissociation (high protein 
with low number of nucleated cells). The CSF 
analysis is indicated to exclude infectious 
etiology, not to diagnose astrocytoma.
IMAGING
• MRI of brain is ideal for mass lesion 
confirmation, as it is superior to CT 
scanning for detecting lesions in the middle 
and caudal fossae. MRI is more sensitive 
than CT for detection infarcts, bleeding, and 
edema. • Brain MRI is useful in establishing 
a tentative differential diagnosis of a glial tumor, based on tumor characteristics 
highlighted in specific sequences.
• Neurologic exam. • Ophthalmic exam. 
• MRI. • CSF analysis. • T umor biopsy for 
definitive diagnosis, when specific antineo-
plastic treatment is sought (surgery, curative-
intent radiation therapy, experimental 
therapies).
  TREATMENT
• Surgery. • Radiation therapy can be very 
effective in improving neurologic signs. 
• Chemotherapy with lomustine, procar-
bazine, or temozolomide might exert cyto  - 
reductive activities. • Anti-inflammatory 
dosing with corticosteroids to reduce 
peritumoral edema. • Consultation with a 
neurosurgeon and a radiation oncologist is 
essential for appropriate patient management.
Seizure Control
• Status epilepticus—diazepam (0.5–1 mg/kg 
IV, up to three times to achieve effect); if no 
response to diazepam, use pentobarbital 
(5–15 mg/kg IV slowly to effect). • Long-
term management—phenobarbital (1–4 mg/kg 
PO q12h) with or without adjuvant potassium 
bromide (20 mg/kg PO q24h).
Tumor Control
• Timely consultation with a neurosurgeon is of 
paramount importance for appropriate manage  - 
ment of the patient. • Radiation therapy may 
be effective, and consultation with a radiation 
oncologist is recommended. Stereotactic 
radiosurgery or intensity-modulated radiation 
therapy may be considered as first-line 
treatment options. • Chemotherapy may be 
effective for treating dogs. Potential drugs that 
may exert measurable anticancer effects include 
CCNU (60–70 mg/m2 PO every 3 weeks) or 
temozolomide (100–120 mg/m2 PO q24h for 
5 days every 3 weeks). • Prednisone (1 mg/kg 
q24h) may be effective in reducing peritumoral 
edema and improving neurologic signs. Patients 
may need to be on steroids long term, even after 
the definitive treatment of the tumor.
• Prednisone and phenobarbital may cause 
polyphagia, polydipsia, and polyuria. 
• Phenobarbital may cause sedation for up 
to 2 weeks after initiation of treatment, and increase in hepatic enzymes on serum 
biochemical panel. • CBC and platelet 
count are recommended 7–10 days after 
chemotherapy and immediately before 
each dose of chemotherapy to monitor 
myelosuppression. • Chemotherapy has 
the potential to be synergistic with 
radiation therapy. Timely referral to a 
specialty center with neurosurgery, 
radiation therapy, and medical oncology 
capabilities is important for patients 
seeking more than palliative care.
  FOLLOW-UP
• Blood phenobarbital concentration should 
be assessed after 7–10 days of treatment, with 
modifications to dosages for achieving target 
plasma concentrations. • Serial MRIs should 
be considered for documenting response if 
multimodality therapy is used. • Serial CBC 
and platelet counts should be performed to 
monitor myelotoxicity associated with 
chemotherapy.
• Long-term prognosis is guarded. 
• Median survival after chemotherapy plus 
medical management may be up to 7 months. 
• Median survival after radiation therapy 
has been reported to be as high as 12 
months.
SEE ALSO
• Seizures (Convulsions, Status Epilepticus)—  
Cats
Dogs
Bentley RT, Ober CP , Anderson KL, et al. 
Canine intracranial gliomas: relationship 
between magnetic resonance imaging criteria 
and tumor type and grade. Vet J 2013, 
198(2):463–471.
Stoica G, Levine J, Wolff J, Murphy K. 
Canine astrocytic tumors: a comparative 
review. Vet Pathol 2011, 48(1):266–275.
T roxel MT, Vite CH, Van Winkle TJ, et al. 
Feline intracranial neoplasia: retrospective 
review of 160 cases (1985–2001). J Vet Intern 
Med 2003, 17:850–859.
Consulting Editor  Timothy M. FanAstrocytoma

130  Blackwell’s Five-Minute Veterinary Consult  
A
  BASICS
• A sign of sensory dysfunction causing loss 
of coordination of the limbs, head, and/or 
trunk.
• Three clinical types—sensory (proprioceptive), 
vestibular, and cerebellar. All cause limb 
incoordination, but only vestibular and 
cerebellar ataxia cause head and neck 
incoordination.
Sensory (Proprioceptive)
• Proprioceptive pathways in the spinal cord 
(i.e., fasciculus gracilis, fasciculus cuneatus, 
and spinocerebellar tracts) relay limb and 
trunk positions to the brain.
• When the spinal cord is slowly compressed, 
proprioceptive deficits are usually the first signs 
observed, because these tracts or pathways are 
located more superficially in the white matter 
and their larger axons are more susceptible to 
compression than are other tracts.
• Limb weakness (paresis) will occur if more 
centrally located motor tracts or pathways 
become involved; weakness is not always 
obvious early in the course of the disease.
• Ataxia can occur with spinal cord, brainstem, 
and cerebral lesions. Ataxia can be mild to 
absent with unilateral brainstem lesions, and 
subtle to absent with unilateral cerebral lesions.
Vestibular
• Changes in balance and head and neck 
positions are detected by vestibular receptors 
of the inner ear, relayed to the vestibulo­
cochlear nerve, which is connected to 
vestibular nuclei in the brainstem.
• The inner ear’s vestibular receptors and nerve 
are components of the peripheral nervous 
system, whereas brainstem vestibular nuclei are 
components of the central nervous system.
• Vestibular ataxia should be localized to 
either the peripheral or central vestibular 
nervous system, because prognosis and 
rule­outs differ for these two locations.
• Both locations of vestibular disease cause 
various degrees of vestibular ataxia, often 
manifested by head tilt and leaning, falling, 
or even rolling toward the side of the lesion.
• Central vestibular disease usually has 
vertical nystagmus or changing types of 
nystagmus; somnolence, stupor, or coma (due 
to involvement of the nearby ascending 
reticular activating system); multiple cranial 
nerve signs (e.g., trigeminal or facial nerve 
deficits); proprioceptive deficits and 
quadriparesis or hemiparesis.
• Peripheral vestibular disease does not 
typically show changes in mental status, 
vertical nystagmus, proprioceptive deficits, 
quadriparesis, or hemiparesis.• Bilateral vestibular disease is uncommon and 
most often peripheral in origin. Typical 
vestibular signs are absent. Wide swinging back 
and forth head motions and poor to absent 
physiologic nystagmus are characteristic.
Cerebellar
• The cerebellum regulates, coordinates, and 
modulates motor activity.
• Proprioception is normal because the 
ascending proprioceptive pathways to the 
cortex are intact; weakness does not occur 
because the upper motor neurons are intact.
• While strength is preserved, affected 
animals have uncoordinated motor activity of 
limbs, head, and neck manifested by hyper  ­ 
metria; dysmetria; head tremors; intention 
tremors; and truncal sway. Menace responses 
may be absent without visual dysfunction.
Nervous—spinal cord (and brainstem and 
cortex), cerebellum, vestibular system.
Any age, breed, or sex.
SIGNS
• Important to define the type of ataxia to 
localize the problem.
• Only one limb involved—rule out a 
musculoskeletal problem.
• Only hind limbs affected—likely a spinal cord 
disorder affecting the spinocerebellar tracts.
• All limbs or ipsilateral limbs affected—  
cervical spinal cord or cerebellar 
localization.
• Head tilt and/or nystagmus—vestibular localiz ­ 
ation.
CAUSES
• Degenerative—abiotrophy (Kerry blue 
terrier, Gordon setter, rough ­coated collie, 
Australian kelpie, Airedale, Bernese mountain 
dog, Finnish harrier, Brittany spaniel, border 
collie, beagle, Samoyed, wirehaired fox terrier, 
Labrador retriever, Great Dane, chow chow, 
Rhodesian ridgeback, domestic shorthair 
cats); storage diseases often have cerebello­
medullary involvement.
• Anomalous—hypoplasia secondary to 
perinatal infection with panleukopenia virus 
(cats); malformed cerebellum due to 
herpesvirus infection (newborn puppies); 
arachnoid or epidermoid cyst located near 
fourth ventricle.
• Neoplastic—any CNS tumor (primary or 
secondary) localized to the cerebellum.
• Infectious—canine distemper virus; feline 
infectious peritonitis (FIP); and any other 
CNS infection affecting the cerebellum.
• Inflammatory, idiopathic, immune ­ 
mediated—meningoencephalomyelitis of 
undetermined etiology.
• Toxic—metronidazole.Vestibular—CNS
• Infectious—FIP; canine distemper virus; 
rickettsial diseases.
• Nutritional—thiamine deficiency.
• Toxic—metronidazole.
Vestibular—Peripheral Nervous System
• Infectious—otitis media interna; 
Cryptococcus  granuloma (cats).
• Inflammatory—nasopharyngeal (middle 
ear) polyps (cats).
• Idiopathic—geriatric vestibular disease 
(dogs); idiopathic vestibular syndrome 
(cats).
• Metabolic—hypothyroidism.
• Neoplastic—squamous cell carcinoma, 
bone tumors.
• T raumatic.
Spinal Cord
• Degenerative—degenerative myelopathy 
(old German shepherd, pug, boxer, Welsh 
corgi, others); degenerative disc disease.
• Vascular—fibrocartilaginous embolic 
myelopathy.
• Anomalous—hemivertebrae; dens hypo  ­ 
plasia with atlantoaxial subluxation ­luxation; 
Chiari ­like malformation; cervical 
spondylomyelopathy; spinal subarachnoid 
diverticulum; other spinal cord and vertebral 
• Neoplastic—primary bone tumors; multiple 
myeloma and metastatic tumors that infiltrate 
the vertebral body; meningioma; others.
• Infectious—discospondylitis; myelitis.
• T raumatic—intervertebral disc herniation; 
fracture or luxation; atlantoaxial subluxation ­ 
luxation.
Metabolic
• Anemia.
• Polycythemia.
• Electrolyte disturbances—especially 
hypokalemia, hypocalcemia, and hypoglycemia.
Miscellaneous
• Drugs—acepromazine; antihistamines; 
antiepileptic drugs; flea and tick products.
• Respiratory compromise.
• Cardiac compromise—reverse patent 
ductus arteriosus, aortic thromboembolism.
• Intervertebral disc disease—dachshund, 
poodle, cocker spaniel, beagle, and others.
• Cervical spondylomyelopathy—Doberman 
pinscher and Great Dane.
• Fibrocartilaginous embolism—young, 
large­breed dogs and miniature schnauzers.
• Dens hypoplasia and atlantoaxial luxation—  
small ­breed dogs, poodles.
• Chiari ­like malformation—cavalier King 
Charles spaniel, small ­breed dogs.Ataxia

Canine and Feline, Seventh Edition  131
A
  DIAGNOSIS
• Differentiate the types of ataxia.
• Differentiate from other disease processes 
that can affect gait—musculoskeletal, 
metabolic, cardiovascular, respiratory.
• Musculoskeletal disorders—typically 
produce lameness, pain, and a reluctance to 
move; degenerative joint disease signs often 
improve with increased movements.
• Systemic illness and endocrine, cardiovascular, 
and metabolic disorders—can cause intermittent 
ataxia, especially of the pelvic limbs; with fever, 
weight loss, murmurs, arrhythmias, hair loss, or 
collapse with exercise, suspect a non ­neurologic 
cause; obtain minimum data from hemogram, 
biochemistry, and urinalysis.
• Head tilt or nystagmus—likely vestibular 
• Intention tremors of the head or hyper ­ 
metria—likely cerebellar localization.
• All four limbs affected—lesion is in the 
cervical spinal cord, cerebellum, or is multifocal 
to diffuse.
• Only pelvic limbs affected—lesion is 
anywhere below the second thoracic vertebra.
Normal unless metabolic cause (e.g., hypo ­ 
glycemia, electrolyte imbalance, anemia, 
polycythemia).
• Hypoglycemia—determine serum insulin 
concentration on sample that has low glucose 
value; low glucose and higher than expected 
insulin value suggest insulin ­secreting tumor.
• Anemia—differentiate as nonregenerative or 
regenerative on the basis of the reticulocyte count.
• Electrolyte imbalance—correct the problem; 
see if ataxia resolves.
• Antiepileptic drugs—if being administered, 
evaluate serum concentration for toxicity.
IMAGING
• Spinal radiography, myelography, CT, 
or MRI—if spinal cord dysfunction suspected.• Bullae radiography—if peripheral vestibular 
disease suspected; CT or MRI superior; for 
inner ear disease, MRI superior to CT.
• Thoracic radiography—for older patients 
and patients suspected to have neoplasia or 
systemic fungal infection.
• CT or MRI—if cerebellar disease suspected; 
MRI superior to CT.
• Abdominal ultrasonography—if hepatic, 
renal, adrenal, or pancreatic dysfunction 
• Cerebrospinal fluid analysis—helps confirm 
nervous system etiology.
• Cerebrospinal fluid culture, antibody titer, 
or polymerase chain reaction—helps confirm 
nervous system infectious etiology.
  TREATMENT
• Usually outpatient, depending on severity 
and acuteness of clinical signs.
• Exercise—decrease or restrict if ataxia 
originates from spinal cord disease.
• Client should monitor gait for increasing 
dysfunction or weakness; if paresis worsens or 
paralysis develops, other testing is warranted.
• Avoid drugs that could contribute to the 
problem; may not be possible in patients on 
antiepileptic drugs for seizures.
Not recommended until the source or cause 
of the problem is identified.
  FOLLOW-UP
Periodic neurologic examinations to assess 
condition.POSSIBLE COMPLICATIONS
• Spinal cord—progression to weakness and 
possibly paralysis.
• Hypoglycemia—seizures.
• Cerebellar disease—head tremors and 
bobbing.
• Brainstem disease—stupor, coma, death.
SEE ALSO
• Cerebellar Degeneration.
• Head Tilt.
• Paralysis.
Cherubini GB, Lowrie M, Anderson J. Pelvic 
limb ataxia in the older dog. In Pract 2008, 
30:386–391.
Davies C, Shell L. Neurological problems. In: 
Davies C, Lawrence T, Shell L, eds., 
Common Small Animal Medical Diagnoses: 
An Algorithmic Approach. Philadelphia, 
PA: Saunders, 2002, pp. 36–59.
Lowrie M. Vestibular disease: anatomy, 
physiology, and clinical signs. Compend 
Contin Educ Vet 2012, 34:E1–5.
Penderis J. The wobbly cat: diagnostic and 
therapeutic approach to generalised ataxia. J 
Fel Med Surg 2009, 11:349–359.
Rossmeisl JH Jr. Vestibular disease in dogs 
and cats. Vet Clin North Am Small Anim 
Pract 2010, 40:81–100.
Author  Linda G. Shell
available online(continued)  Ataxia

132  Blackwell’s Five-Minute Veterinary Consult  
A
  BASICS
OVERVIEW
• Results from malformation or disruption of 
the articulation between the first and second 
cervical vertebrae (atlas and axis, respectively); 
causes spinal cord compression.
• Can result in spinal cord trauma or 
compression at the junction between atlas and 
axis—may cause neck pain and/or varying 
degrees of general proprioceptive (GP) ataxia/
upper motor neuron (UMN) tetraparesis, 
tetraplegia (with or without nociception), and 
death from respiratory arrest.
Etiology
• Congenital—anomaly of the dens (aplasia, 
hypoplasia, or malformation [dorsal angulation] 
of the dens) and its ligamentous attachments.
• Acquired—consequence of traumatic 
injury.
• Congenital—toy-breed dogs (Yorkshire 
terrier, miniature or toy poodle, Chihuahua, 
Pekingese, and Pomeranian).
• Age at onset—usually before 12 months.
• Uncommon in larger-breed dogs, dogs >1 
year old, and cats.
• No sex predilection.
SIGNS
• Intermittent or progressive ambulatory 
tetraparesis, usually with neck pain—most 
common.
• Neurologic signs vary from mild to 
moderate GP/UMN ambulatory tetraparesis 
to nonambulatory GP/UMN tetraparesis, or 
tetraplegia, depending on degree of spinal 
cord compression and secondary pathology 
(i.e., edema, hemorrhage, or gliosis).
• Animals may have only neck pain without 
concurrent neurologic deficits.
• Episodes of collapse secondary to weakness.
• Abnormal postural reactions with spinal 
reflexes that are normal to exaggerated, with 
normal to increased muscle tone in all four 
limbs.
• Acute death may occur when accompanied 
by trauma and respiratory arrest (uncommon).
• Usually caused by abnormal development 
of the dens and/or ligamentous support 
structures, resulting in subluxation of the 
atlantoaxial joint.
• Fracture of the axis.
• Clinical signs often occur as a result of mild 
or insignificant trauma (e.g., jumping or 
playing).
• Clinical signs may be exacerbated by 
activity such as flexion of the neck.
• Toy-breed dogs—at risk for congenital 
malformation of the dens.  DIAGNOSIS
• Differential diagnoses are consistent with 
various causes of cervical myelopathies, 
including:
◦ Other congenital malformation.
◦ T rauma.
◦ Meningitis or meningomyelitis, infectious 
or noninfectious (granulomatous 
meningoencephalomyelitis).
◦ Fibrocartilaginous embolic myelopathy.
◦ Disk herniation.
◦ Neoplasia.
Normal
IMAGING
• Plain radiography of the cervical vertebral 
column:
◦ Lateral view—caudal and dorsal displace  - 
ment of the axis in relationship to the atlas, 
resulting in increased distance between 
◦ Ventral dorsal or oblique view—may 
reveal absence, hypoplasia, or malformation 
(dorsal angulation) of the dens.
• Cross-sectional imaging:
◦ MRI.
◦ Diagnosis based on observation of caudal 
and dorsal displacement of the axis in 
relationship to the atlas, as evidenced by the 
following features of the atlantoaxial 
articulation: (1) dorsal: displacement of the 
spinous process of the axis; (2) ventral: 
increased size of the occipito-atlas-axis joint 
cavity.
◦ Allows identification of spinal cord 
compression.
◦ Allows recognition of secondary spinal 
cord pathology such as edema, hemorrhage, 
or gliosis, which may impact prognosis.
• CT—may provide detailed visualization of 
bony structures, which allows for creation of 
three-dimensional reconstructed image to 
help surgical planning.
• Precautions:
◦ Proper positioning will require sedation 
or general anesthesia.
◦ Sedation or general anesthesia carries 
significant risk for iatrogenic trauma.
◦ Care needs to be exercised when 
positioning animals.
◦ Avoid  excessive  flexion of the neck!
◦ Flexion may exacerbate compression, 
which may worsen clinical signs or cause 
death due to spinal cord trauma.
◦ To protect against neck flexion during 
recovery, affected animals should be closely 
monitored until they are capable of 
maintaining normal head and neck carriage.  TREATMENT
• Prior to treatment, consultation with a 
board-certified neurologist or surgeon should 
be pursued.
• Improper treatment can lead to irreversible 
deterioration in neurologic function.
MEDICAL
• Neck brace (splint) to stabilize cervical 
vertebral column in extension.
◦ Fiberglass cast material positioned 
ventrally from rostral aspect of mandible to 
xiphoid and incorporated into bandage 
material, which immobilizes head and 
neck.
◦ Strict exercise restriction (cage confine-
ment) for minimum of 8 weeks.
◦ Frequent bandage/splint changes are 
needed.
• Adjunctive medication (see below).
Overall Prognosis
• Successful outcome observed in 62.5% 
of dogs.
• Improved prognosis associated with acute 
onset and short duration of clinical signs 
(<30 days).
• Surgery recommended to treat animals that 
fail to improve or experience recurrence of 
signs following medical treatment.
SURGERY
• T reatment of choice in majority of cases.
• Surgical approach; ventral method is 
preferred .
• Ventral approach—variety of methods:
◦ T ransarticular pinning or lag screw 
technique; ventral tips of pins incorporated 
in polymethylmethacrylate to prevent pin 
migration.
◦ T ransarticular pinning and ventral 
cortical screws or K-wires in bodies of atlas 
and axis ± K-wires applied longitudinally 
and wired to screws; screw heads and 
K-wires incorporated in polymethylmeth-
acrylate to provide fixation.
• Dorsal approach—use wire or synthetic 
suture material to fix spinous process of axis 
to dorsal arch of atlas; provides less rigid 
fixation and may be associated with greater 
implant failure.
• Strict exercise restriction required for 
first month postoperatively, followed by 
gradual return to activity over additional 
month.
• Overall prognosis ranges from 63% to 91% 
success—improved prognosis associated with 
young ( <24 months) dogs, duration of clinical 
signs <10 months, and mild neurologic 
deficits.Atlantoaxial Instability

Canine and Feline, Seventh Edition  133
A
• Complications:
◦ Failure to improve/worsening of neuro- 
logic deficits.
◦ Implant failure/infection.
◦ Respiratory—respiratory arrest, dyspnea, 
cough, and aspiration pneumonia.
◦ Death.
• Anti-inflammatory medication:
◦ Corticosteroids—prednisone 0.5–
1.0 mg/kg PO divided twice daily for 
2 weeks, followed by tapering regime. 
Suggested protocol following initial dose: 
0.5 mg/kg PO daily for 5 days, followed by 
0.5 mg/kg PO every other day for 5 days.
◦ Nonsteroidal anti-inflammatory drug 
(NSAID)—1- to 4-week course.
• Analgesia:
◦ T ramadol 2.0–4.0 mg/kg PO q6–8h—
questionable efficacy.
◦ Gabapentin 10–20 mg/kg PO q6–8h.
◦ Pregabalin 3–4 mg/kg (begin with 2 mg/
kg) PO q8–12h.
• Corticosteroid—use caution when given in 
conjunction with medical treatment; may 
reduce pain, resulting in increased activity 
and spinal cord trauma.
• Avoid NSAIDs in combination with 
corticosteroids in all patients—increases risk 
of life-threatening gastrointestinal 
hemorrhage.  FOLLOW-UP
• Dogs treated medically require frequent 
(weekly) bandage changes for associated soft 
tissue trauma.
• All dogs should be reevaluated at 1 and 3 
months (postoperatively or after neck brace 
removal) and then monthly until neurologic 
deficits resolve or remain static over 2–3 
months.
• More frequent rechecks may be needed for 
dogs experiencing complications or recur-
rence of signs.
• Untreated animals may experience 
deterioration in neurologic function, 
catastrophic acute spinal cord trauma, 
respiratory arrest, and death.
• Rehabilitation may play a significant role 
in ultimate neurologic functional level of 
patient.
• Rehabilitation should only be considered 
in dogs >30 days postoperatively or after 
neck brace (splint) removal.
• GP = general proprioceptive.
drug.
• UMN = upper motor neuron.
www.acvs.org/small-animal/
atlantoaxial-instability Suggested Reading
Beaver DP , Ellison GW, Lewis DD. Risk 
factors affecting the outcome of surgery for 
atlantoaxial subluxation in dogs: 46 cases 
(1978–1998). J Am Vet Med Assoc 2000, 
216(7):1104–1109.
Havig ME, Cornell KK, Hawthorne JC, et al. 
Evaluation of nonsurgical treatment of 
atlantoaxial subluxation in dogs: 19 cases 
(1992–2001). J Am Vet Med Assoc 2005, 
227(2):257–262.
McCarthy RJ, Lewis DD, Hosgood G. 
Atlantoaxial subluxation in dogs. Compend 
Contin Educ Pract Vet 1995, 17:215–226.
Platt SR, Casimiro da Costa R. Cervical 
vertebral column. In: Johnston SA, Tobias 
KM, eds., Textbook of Small Animal 
Surgery, 2nd ed. St. Louis, MO: Elsevier, 
2018, pp. 438–485.
Platt SR, Chambers JN, Cross A. A modified 
ventral fixation for surgical management of 
atlantoaxial subluxation in 19 dogs. Vet 
Surg 2004, 33(4):349–354.
Sanders SG, Bagley RS, Silver GM, et al. 
Outcomes and complications associated 
with ventral screws, pins, and polymethyl 
methacrylate for atlantoaxial instability in 
12 dogs. J Am Anim Hosp Assoc 2004, 
40:204–210.
Schulz KS, Waldron DR, Fahie M. 
Application of ventral pins and polymethyl-
methacrylate for the management of 
atlantoaxial instability: results in nine dogs. 
Vet Surg 1997, 26(4):317–325.
Author  Mathieu M. Glassman
Consulting Editor  Mathieu M. Glassman(continued)  Atlantoaxial Instability

134  Blackwell’s Five-Minute Veterinary Consult  
A
  BASICS
• Genetically predisposed skin disease 
characterized by inflammation and pruritus. 
Clinical signs associated with immunoglobulin 
(Ig) E and most commonly directed against 
environmental allergens. • Differentiate from 
atopic-like dermatitis, in which clinical signs 
identical to atopic dermatitis but IgE response 
to environmental or other allergens cannot be 
demonstrated.
• Allergen exposure in susceptible animals 
results in IgE production. Upon reexposure to 
allergen, mast cell degranulation and activation  
of TH2 lymphocytes allow release of 
inflammatory cytokines, chemokines, 
histamine, proteolytic enzymes, and other 
chemical mediators. • Genetic defects—dogs: 
gene expression upregulated or downregulated; 
cats: not well documented. • Barrier function 
defects—dogs: impaired epidermal lipid 
barrier can lead to enhanced allergen 
penetration and increased transepi  dermal 
water loss (TEWL); filaggrin defect thought 
to be associated; cats: may not be as relevant 
as with dogs. • Immunologic defects—dogs: 
acute lesions characterized by increased TH2 
lymphocyte activity, while TH1 cytokines 
predominate in chronic lesions; TH2:TH1 
imbalance proposed; aberrant regulatory 
T-cell function reported; cats: TH2-mediated 
dysfunction suspected, but cytokine pathways 
need further investigation. • Bacterial 
superantigens, auto-antigens released via 
keratinocyte damage, and Malassezia  may 
play role in inflammation.
• Ophthalmic. • Respiratory. • Skin/exocrine.
GENETICS
• Dogs—inherited predisposition. • Cats—
inherited predisposition less clear.
• Canine—3–27% of canine population 
estimated. • Feline—lower than for dogs.
Canine—worldwide; local factors influence 
seasonality, severity, and duration of signs.
Species
• United States—Boston terrier, boxer, 
Cairn terrier, Chinese Shar-Pei, cocker 
spaniel, Dalmatian, English bulldog, English 
and Irish setter, American Staffordshire 
terrier, Lhasa apso, miniature schnauzer, 
pug, Sealyham terrier, Scottish terrier, West Highland white terrier, wirehaired fox 
terrier, Labrador retriever. • Feline—
Abyssinian, Devon Rex, domestic 
 shorthaired cats.
• Canine—6 months to 3 years. • Feline—6 
months to 2 years, commonly under 3 years.
None reported.
SIGNS
Cutaneous changes caused by self-induced 
trauma; primary lesions usually unrecognized.
• Pruritus. • Early age of onset. •History in 
related individuals. • May be initially 
seasonal. • Recurring skin or ear infection. 
• Temporary response to glucocorticosteroids. 
• Signs worsen with time.
• Most common (dogs)—interdigital spaces, 
carpal/tarsal areas, muzzle, periocular, 
axillae, abdomen, pinnae; >40% can be 
generalized. • Most common (cats)—head 
and neck, mouth, abdomen, lateral thorax, 
hind limbs. • Lesions (dogs)—none to 
salivary staining, alopecia, erythema, papules, 
crusts, hyperpigmentation, lichenification, 
seborrhea sicca/oleosa, and/or hyperhidrosis. 
• Lesions (cats)—miliary dermatitis (small 
crusted papules), alopecia, eosinophilic 
granuloma complex (indolent ulcers, 
eosinophilic granulomas, eosinophilic 
plaques). • Chronic relapsing bacterial and 
yeast skin/ear infections (common). 
• Respiratory symptoms, conjunctivitis, and 
blepharitis possible.
CAUSES
• Pollens. • Mold spores. • Malassezia . 
• House dust and storage mites. • Animal/
human dander. • Insects.
• Environments with long allergy seasons and 
high pollen and mold spore levels. • Concurrent 
hypersensitivities (summation effect). • Born 
during allergy season. • Breed predisposition.
  DIAGNOSIS
• Adverse food reaction. • Flea bite hyper -
sensitivity. • Sarcoptic mange. • Bacterial 
folliculitis. • Yeast dermatitis. • Contact 
dermatitis (allergic or irritant).
Eosinophilia—rare in dogs without  concurrent 
flea infestations; common in cats.DIAGNOSTIC PROCEDURES
• Diagnosis made by history, physical exam -
ination, and ruling out differential diagnoses. 
• Serology/intradermal test (IDT) not meant for 
diagnosis. • Greatest treatment success noted 
when immunotherapy based on results of both 
serum and intradermal testing.
Serologic Allergy Tests
• Measures allergen-specific IgE in serum. 
• Advantages—readily available; clipping/
sedation not required; concurrent/recent 
medications and infections less likely to affect 
results; similar hyposensitization success to 
IDT. • Disadvantages—fewer allergens tested; 
quality control/reliability varies with laboratory.
IDT
• Test allergens injected intradermally causing 
wheal formation. • Advantages—tests 
affected organ, results available immediately, 
many allergens tested; preferred where 
available. • Disadvantages—requires 
experience to interpret results, clipping and 
sedation needed, difficult to interpret in cats; 
drug withdrawal periods recommended, 
concurrent infection may affect results.
Skin biopsy—rule out other differential 
diagnoses; results not pathognomonic; 
superficial perivascular dermatitis with 
lymphocytic exocytosis ± eosinophils, mast 
cells; often with secondary bacterial folliculitis.
  TREATMENT
ACTIVITY
Avoid offending allergens when possible.
DIET
Diets rich in essential fatty acids may be beneficial.
Explain inheritable, progressive, and incurable 
nature of condition.
Immunotherapy (Hyposensitization)
• Subcutaneous or sublingual administration 
of causative allergens. • Allergen selection 
based on allergy test results, patient history, 
and knowledge of local exposure. 
• Immunotherapy protocols not standardized 
and vary widely between clinicians. 
• Preferred treatment in most cases. 
• Successfully reduces pruritus in 50–90% 
of dogs and cats. • 3 months to 1 year for full 
effect. • May continue lifelong if effective.Atopic Dermatitis

Canine and Feline, Seventh Edition  135
A
Cyclosporine (Atopica® Preferred)
• Cyclosporine, modified (dogs, 5 mg/kg/
day; cats, 7 mg/kg/day). • 1–4 weeks for 
effect—frequency of dosing may be reduced 
to maintain control of symptoms. 
• Monitoring recommended. • Cats—drug 
blood level monitoring recommended; keep 
indoors, do not feed raw meat.
• For short-term relief or taper to lowest 
dosage/frequency. • Dogs—e.g., prednisolone 
(1 mg/kg PO q24h). • Cats—e.g., 
prednisolone (2 mg/kg q24h).
Antihistamines
• Less effective than corticosteroids. • 2 weeks 
for effect. • Dogs—cetirizine (1 mg/kg PO 
q12–24h), chlorpheniramine (0.4 mg/kg PO 
q8–12h), diphenhydramine (2.2 mg/kg PO 
q8–12h), amitriptyline (1–2 mg/kg q12h). 
• Cats—cetirizine (5 mg/cat q24h), 
chlorpheniramine (2 mg/cat PO q12h), 
amitriptyline (5–10 mg/cat q24h); 
diphenhydramine may cause paradoxical 
excitation in cats.
Oclacitinib  (Apoquel®)
• Dogs—onset time/response similar to 
glucocorticoids (0.4–0.6 mg/kg q12h for 14 
days, then q24h for maintenance). • Cats—
not licensed; limited short-term studies report 
effectiveness, but higher doses may be needed.
Lokivetmab (Cytopoint®)
Dogs only—anti-IL-31 monoclonal antibody 
injectable; repeated as needed up to frequency 
of every 4–6 weeks.
• Immunotherapy—anaphylaxis rare 
(accompanied by diarrhea, weakness, 
collapse), hives, facial swelling; monitor for 
1 hour post injection; increased pruritus 
after injection may indicate change in 
schedule needed; pain or swelling at 
injection site uncommon. • Cyclosporine—
may affect glucose homeostasis; increased 
incidence of urinary tract infection; 
vomiting and diarrhea most common side 
effects; gingival hyperplasia, papillomavirus, 
and hirsutism possible; risk of fatal toxoplasmosis 
in naïve cats. • Corticosteroids—avoid 
iatrogenic hyperglucocorticism/
hyperadrenocorticism; possible aggravation 
of pyoderma and induction of demodicosis. 
• Antihistamines—can produce drowsiness, 
rarely anorexia, vomiting, diarrhea, increased 
pruritus; use with caution in patients with 
cardiac arrhythmias. • Oclacitinib—not for use in dogs under 1 year of age; may cause 
existing parasitic skin infestations and/or 
prevent resolution of infections.
Concurrent use of cyclosporine and ketoconazole 
permits 50% dose reduction of each drug.
• Frequent bathing (once to twice weekly) in 
cool water with antipruritic, antibacterial, 
antifungal, and/or moisturizing shampoos can 
be beneficial. • Fatty acids—diets rich in 
essential fatty acids typically provided higher 
amounts than with oral supplements. 
• Pentoxifylline 25 mg/kg q12h. • Topical 
hydrocortisone or triamcinolone spray 
0.015% (short-term use).
  FOLLOW-UP
• Examination every 2–8 weeks initially; once 
acceptable level of control achieved, examine 
every 3–6 months. • Monitor pruritus, self- 
trauma, development of secondary infection, 
possible adverse drug reactions. • CBC/blood 
chemistry/urinalysis with culture—
recommended every 3–12 months for 
patients on chronic corticosteroid, 
cyclosporine, or oclacitinib therapy.
• Avoidance of allergens seldom possible. 
• Minimize other sources of pruritus.
• Secondary bacterial folliculitis or 
Malassezia  dermatitis. • Concurrent 
hypersensitivities.
• Pruritus and duration of signs usually 
worsen over time without intervention. 
• Some cases spontaneously resolve.
• Hypersensitivity (flea, food). • Bacterial 
folliculitis. • Malassezia  dermatitis. • Otitis 
externa.
Severity worsens with age.PREGNANCY/FERTILITY/BREEDING
• Corticosteroids—contraindicated during 
pregnancy. • Affected animals should not be 
used for breeding.
SYNONYMS
• Atopy. • Canine atopic disease.
SEE ALSO
• Eosinophilic Granuloma Complex. 
• Flea Bite Hypersensitivity and Flea Control. 
• Food Reactions, Dermatologic. 
• Otitis Externa and Media. 
• Pyoderma.
• IDT = intradermal test. 
• Ig = immunoglobulin. 
• TEWL = transepidermal water loss.
Botoni LS, Torres SMF , Koch SN, et al. 
Comparison of demographic data, disease 
severity, and response to treatment, between 
dogs with atopic dermatitis and atopic-like 
dermatitis: a retrospective study. Vet Derm 
2019, 30:10–e4.
Gedon NK, Mueller RS. Atopic dermatitis 
in cats and dogs: a difficult disease for 
animals and owners. Clin T ransl Allergy 
2018, 8:41.
Lappin MR, VanLare KA, Seewald W, et al. 
Effect of oral administration of cyclosporine 
on Toxoplasma gondii infection status of 
cats. Am J Vet Res 2015, 76(4):351–357.
7th ed. St. Louis, MO: Elsevier Mosby, 
2013.
Noli C, Matricoti I, Schievano C. A double 
blinded, randomized, methylprednisolone-
controlled study on the efficacy of oclacitinib 
in the management of pruritus in cats with 
nonflea nonfood induced hypersensitivity 
dermatitis. Vet Derm 2019, 
30(2):110–e30.
Resnick
available online(continued)  Atopic Dermatitis

136  Blackwell’s Five-Minute Veterinary Consult  
A
  BASICS
• Atrial fibrillation—rapid, irregularly irregular 
supraventricular rhythm. T wo forms recognized: 
primary atrial fibrillation, an uncommon disease 
that occurs mostly in large dogs with no under  - 
lying cardiac disease; and secondary atrial 
fibrillation, which occurs in dogs and cats 
secondary to underlying cardiac disease. • Atrial 
flutter is similar to atrial fibrillation, but the 
atrial rate is generally slower and is character -
ized by saw-toothed flutter waves in the baseline 
of the ECG. The ventricular response is generally 
rapid, but may be regular or irregular.
ECG Features
Atrial Flutter
• Atrial rhythm usually regular; rate approx  - 
imately 300–400 bpm. • P waves usually 
discerned as either discrete P waves or “saw- 
toothed” baseline. • Ventricular rhythm and 
rate generally depend on atrial rate and 
atrioventricular (AV) nodal conduction, but 
are generally regular or regularly irregular and 
rapid. • Conduction pattern to ventricles is 
variable—in some cases every other atrial 
depolarization produces a ventricular 
depolarization (2 : 1 conduction ratio), giving 
a regular ventricular rhythm (Figure 1); other 
times the conduction pattern appears 
random, giving an irregular ventricular 
rhythm that can mimic atrial fibrillation.
Secondary Atrial Fibrillation
• No P waves present—baseline may be 
flat or may have small irregular undulations 
(“f” waves); some undulations may look like 
P waves. • Ventricular rate often elevated—
usually 180–240 bpm in dogs and >220 bpm 
in cats. • Interval between QRS complexes is 
irregularly irregular; QRS complexes usually 
appear normal (Figure  2).
Primary Atrial Fibrillation
Similar to secondary atrial fibrillation, except 
ventricular rate usually in normal range.
• Atrial fibrillation—caused by numerous 
small reentrant pathways creating a rapid 
(>500 depolarizations/minute) and disorgan -
ized depolarization pattern in the atria that 
results in cessation of atrial contraction. 
Depolarizations continuously bombard the AV 
nodal tissue, which acts as a filter and does not 
allow all depolarizations to conduct to the 
ventricles. Many atrial depolarizations activate 
only a part of the atria, because the rapid rate 
renders portions of the atria refractory, and 
thus they cannot reach the AV junction. Other 
atrial impulses penetrate into the AV junc -
tional tissue, but do not penetrate the entire 
length. Blocked impulses affect the conduction 
properties of the AV junctional tissue and alter conduction of subsequent electrical impulses; 
electrical impulses are conducted through the 
AV junction irregularly, producing an irregular 
ventricular rhythm. • Atrial flutter—probably 
originates from one site of reentry that moves 
continuously throughout the atrial myocar -
dium and frequently and regularly stimulates 
the AV node. When the atrial rate becomes 
sufficiently fast, the refractory period of the AV 
node exceeds the cycle length (P to P interval) 
of the supraventricular tachycardia (SVT), and 
some atrial depolarizations are blocked from 
traversing the AV node (functional second-
degree AV block).
Cardiovascular
Loss of atrial contraction may result in 
decreased stroke volume and cardiac output, 
depending on heart rate; high heart rate may 
result in deterioration in myocardial function 
(tachycardia-induced myocardial failure).
GENETICS
No breeding studies available.
Species
Large- and giant-breed dogs more prone to 
primary atrial fibrillation.
N/A
N/A
SIGNS
• Generally relate to underlying disease 
process and/or congestive heart failure 
(CHF) rather than arrhythmia itself, but 
previously stable animals may decompensate. 
• Patients with primary atrial fibrillation are 
generally asymptomatic, but may demonstrate 
mild exercise intolerance.
• Coughing/dyspnea/tachypnea. • Exercise 
intolerance. • Rarely, syncope. • Dogs with 
primary atrial fibrillation are typically 
asymptomatic.
• On auscultation, patients with atrial 
fibrillation have an erratic heart rhythm that 
sounds like “tennis shoes in a dryer.” • First 
heart sound intensity in atrial fibrillation is 
variable; second heart sound only heard on 
beats with effective ejection, not on every beat. 
• Third heart sounds (gallop sounds) may 
be present. • Patients with atrial fibrillation 
have pulse deficits and variable pulse quality. 
• Signs of CHF often present (e.g., cough, 
dyspnea, cyanosis).CAUSES
• Myxomatous valve disease. • Cardiomyopathy. 
• Congenital heart disease. • Digoxin toxicity. 
• Idiopathic. • Ventricular preexcitation 
(atrial flutter).
  DIAGNOSIS
• Frequent atrial (supraventricular) premature 
depolarizations. • Supraventricular tachy -
cardia with AV block. • Multifocal atrial 
tachy  cardia (irregular).
N/A
N/A
IMAGING
• Echocardiography and radiography may 
characterize type and severity of underlying 
cardiac disease; moderate to severe heart 
enlargement common. • Typically normal in 
patients with primary atrial fibrillation, 
although mild left atrial enlargement may 
accompany hemodynamic alterations 
imposed by arrhythmia.
A baseline 24-hour Holter is recommended 
to determine if arrhythmia is chronic or 
paroxysmal. If it is chronic, drug therapy may 
be indicated.
  TREATMENT
• Patients with fast (secondary) atrial 
fibrillation are treated medically to slow the 
ventricular rate. Converting the atrial 
fibrillation to sinus rhythm would be ideal, but 
such attempts in patients with severe underly -
ing heart disease or left atrial enlargement are 
generally futile because of a low success rate 
and high rate of recurrence. Consider electrical 
cardioversion to sinus rhythm for a dog with 
primary atrial fibrillation and minimal 
structural heart disease. • Patients with primary 
atrial fibrillation may be converted back to 
normal sinus rhythm. The success rate depends 
on chronicity. Patients that have been in atrial 
fibrillation for >4 months generally have a 
lower success rate and a higher rate of 
recurrence. In these patients, rate control, if 
necessary, is the recommended treatment. 
• Electrical (DC) cardioversion—application 
of a transthoracic electrical shock at a specific 
time in the cardiac cycle; requires special 
equipment, trained personnel, and general 
anesthesia. Using a monophasic defibrillator: 
start with 4 J/kg; if no conversion occurs, Atrial Fibrillation and Atrial Flutter

Canine and Feline, Seventh Edition  137
A
increase dose by 50 J and repeat until a max of 
360 J. Using a biphasic defibrillator: start with 
1–2 J/kg; if no cardioversion occurs, increase 
dose by 50 J and repeat until max of 360 J. 
• For atrial flutter, conversion to sinus rhythm 
can be accomplished by drug therapy, electrical 
cardioversion, or rapid atrial pacing (trans -
venous pacing electrode).
As indicated for CHF .
ACTIVITY
Restrict activity until tachycardia is controlled.
DIET
Mild to moderate sodium restriction if CHF .
• Secondary atrial fibrillation and atrial 
flutter are usually associated with severe 
underlying heart disease; goal of therapy is 
to lower heart rate and control clinical signs. • Sustained conversion to sinus 
rhythm is unlikely with secondary atrial 
fibrillation.
N/A
• Digoxin, β-adrenergic blockers, esmolol, 
and calcium channel blockers (diltiazem) are 
frequently used to slow conduction through 
the AV node; definition of an adequate heart 
rate response varies among clinicians, but in 
dogs is generally 130–150 bpm. • For atrial 
flutter, therapy is aimed at suppressing the 
atrial reentry circuit using sotalol, amiodar -
one, or procainamide.Dogs
• Digoxin—maintenance oral dose 
0.005–0.01 mg/kg PO q12h; to achieve 
therapeutic serum concentration more 
rapidly, maintenance dose can be doubled 
for the first day. If digoxin is administered 
alone and heart rate remains high, check 
digoxin level and adjust dose to bring level 
into therapeutic range. If heart rate remains 
high, consider adding calcium channel 
blocker or β-adrenergic blocker. 
• Diltiazem—initially administered at dose 
of 0.5 mg/kg PO q8h, then titrated up to 
maximum of 1.5 mg/kg PO q8h or until 
adequate response is obtained. • Therapy 
for atrial flutter is aimed at suppressing 
one, or procainamide. Conversion to 
normal sinus rhythm is usually 
unsuccessful.
Figure 1 .
Atrial flutter with 2 : 1 conduction at a ventricular rate of 330/minute in a 
dog with an atrial septal defect. This supraventricular tachycardia was associ -
ated with a Wolff-Parkinson-White pattern. (Source: From Tilley LP . 
Essentials of Canine and Feline Electrocardiography, 3rd ed. Baltimore, MD: 
Williams & Wilkins, 1992. Reprinted with permission of Wolters Kluwer.)
Figure 2.
“Coarse” atrial fibrillation in a dog with patent ductus arteriosus. The f waves are prominent. 
(Source: From Tilley LP . Essentials of Canine and Feline Electrocardiography, 3rd ed. Baltimore, MD: 
Williams & Wilkins, 1992. Reprinted with permission of Wolters Kluwer.)(continued)  Atrial Fibrillation and Atrial Flutter

138  Blackwell’s Five-Minute Veterinary Consult  
AAtrial Fibrillation and Atrial Flutter  (continued)
Cats
• Diltiazem (1–2.5 mg/kg PO q8h) or 
atenolol (6.25–12.5 mg/cat PO q12–24h) 
are drugs of choice in most cats. • If the 
heart rate is not sufficiently slowed with 
these drugs or myocardial failure is present, 
digoxin (5  μg/kg PO q24–48h) can be 
added.
• Digoxin, diltiazem, propranolol, and 
atenolol should not be used in patients with 
preexisting AV block. • Use of calcium 
channel blockers in combination with beta 
blockers should be avoided because clinically 
significant bradyarrhythmias and/or AV 
block can develop.
• Calcium channel blockers and β-adrenergic 
blockers, both negative inotropes, should be 
used cautiously in animals with myocardial 
failure. • Using high-dose oral quinidine for 
conversion to sinus rhythm carries a risk of 
quinidine toxicity (e.g., hypotension, weak  - 
ness, ataxia, and seizures)—administration of 
diazepam intravenously controls seizures; 
other signs abate within several hours of 
discontinuing quinidine administration.
Quinidine raises the digoxin level, generally 
necessitating a digoxin dose reduction.  FOLLOW-UP
• Monitor heart rate and ECG closely. • As 
heart rates in the hospital and those measured 
on the surface ECG may be inaccurate (due 
to patient anxiety and other environmental 
factors), Holter monitoring provides a more 
accurate means for assessing the need for 
heart rate control and/or the efficacy of 
medical therapy for heart rate control.
Worsening of cardiac function with onset of 
arrhythmia.
• Secondary atrial fibrillation—often 
associated with severe structural heart disease, 
so a guarded to poor prognosis. • Primary 
atrial fibrillation with normal ultrasound 
findings—generally a good prognosis.
• AV = atrioventricular. 
• CHF = congestive heart failure. 
• SVT = supraventricular tachycardia.
Bright JM, Brunnen J. Chronicity of atrial 
fibrillation affects duration of sinus rhythm after transthoracic cardioversion of dogs 
with naturally occurring atrial fibrillation. 
J Vet Intern Med 2008, 22(1):114–119.
Gelzer RM, Kraus MS. Management of atrial 
fibrillation. Vet Clin North Am Small Anim 
Pract 2004, 34:1127–1144.
Gelzer ARM, Kraus MS, Moise NS, et al. 
Assessment of antiarrhythmic drug efficacy 
to control heart rate in dogs with atrial 
fibrillation using 24-hour ambulatory 
electrocardiographic (Holter) recordings. 
J Vet Intern Med 2004, 18(5):779.
Tilley LP , Smith FWK, Jr. Electrocardiography. 
In: Smith FWK, Tilley LP , Oyama M, 
Sleeper M., eds., Manual of Canine and 
Feline Cardiology, 5th ed. St. Louis, MO: 
Saunders Elsevier, 2016, pp. 49–76.
Santilli R, Moise NS, Pariaut R, Perego M. 
Electrocardiography of the Dog and Cat: 
Diagnosis of Arrhythmias, 2nd ed. Milan: 
Edra, 2018.
Tilley LP , Smith, F .W. Essentials of 
Electrocardiography: Interpretation and 
T reatment, 4th ed. Ames, IA: Wiley-
Blackwell, 2016.
Willis R, Oliveira P , Mavropoulou A. Guide 
to Canine and Feline Electrocardiography. 
Ames, IA: Wiley-Blackwell, 2018.
Author  Larry P . Tilley

Canine and Feline, Seventh Edition  139
A
  BASICS
Premature atrial complexes or beats (APC) 
that originate outside the sinoatrial node and 
disrupt the normal sinus rhythm for 1 or 
more beats.
• Heart rate usually normal; rhythm irregular 
due to the premature P wave (called a P ′ 
wave) that disrupts the normal P wave 
rhythm (Figure 1). • Ectopic P ′ wave—  
premature; configuration differs from that of 
the sinus P waves and may be negative, 
positive, biphasic, or superimposed on the 
previous T wave. • QRS complex—  
premature; configuration usually normal 
(same as that of the sinus complexes). If the 
P′ wave occurs during the refractory period of 
the atrioventricular (AV) node, ventricular 
conduction does not occur (nonconducted 
APCs), so no QRS complex follows the P ′ 
wave. If there is partial recovery in the AV 
node or intraventricular conduction systems, 
the P ′ wave is conducted with a long P ′–R 
interval or with an abnormal QRS configura-
tion (aberrant conduction). The more 
premature the complex, the more marked the 
aberration. • In the P–QRS relationship, the 
P′–R interval is usually as long as, or longer 
than, the sinus P ′–R interval. • A noncom-
pensatory pause—when the R–R interval of 
the two normal sinus complexes enclosing an 
APC is less than the R–R intervals of three 
consecutive sinus complexes—usually follows 
an APC (Figure 2). The ectopic atrial impulse 
discharges the sinus node and resets the cycle.
• Mechanisms—an increase in automaticity 
of atrial myocardial fibers or a single reentrant 
circuit. • May be normal finding in aged dogs; commonly seen in dogs with atrial 
enlargement secondary to chronic mitral 
valvular insufficiency; may also be observed 
in dogs or cats with any atrial disease. • May 
not cause hemodynamic problems; the 
clinical significance relates to their frequency, 
timing relative to other complexes, and the 
underlying clinical problems. • Can presage 
more serious rhythm disturbances (e.g., atrial 
fibrillation, atrial flutter, or atrial tachycardia).
GENETICS
N/A
Not documented.
Species
Small-breed dogs.
Geriatric animals, except those with 
congenital heart disease.
SIGNS
• No signs. • Congestive heart failure (CHF).
• Coughing and dyspnea. • Exercise 
intolerance. • Syncope.
• Myxomatous valve disease. • Cardiac murmur.
• Gallop sound. • Signs of CHF .
• Chronic valvular disease. • Congenital 
heart disease. • Cardiomyopathy. • Atrial 
myocarditis. • Electrolyte disorders. 
• Neoplasia. • Hyperthyroidism. • Toxemias. 
• Drug toxicity (e.g., digitalis). • Normal 
variation in aged animals.  DIAGNOSIS
• Marked sinus arrhythmia. • Ventricular 
premature complexes when aberrant 
ventricular conduction follows an APC.
N/A
N/A
IMAGING
Echocardiography and Doppler ultrasound 
may reveal the type and severity of the under  - 
lying heart disease.
• ECG. • Holter monitor to quantify APC 
frequency and event monitor/Holter ECG to 
correlate symptoms with rhythm.
Atrial enlargement; other features vary 
depending on underlying cause.
  TREATMENT
• T reat animal as inpatient or outpatient. 
• T reat the underlying CHF , cardiac disease, 
or other causes.
Usually not necessary; varies with underlying 
cause.
ACTIVITY
Restrict if symptomatic.
DIET
No modifications unless required for 
management of underlying condition 
(i.e., low-salt diet).Atrial Premature Complexes
Figure 1 .
APCs in a dog. P ′ represents the premature P wave. The premature QRS resembles the normal (sinus) QRS. The upright P ′ wave is superimposed on the T wave 
of the preceding complex. (Source: From Tilley LP . Essentials of Canine and Feline Electrocardiography, 3rd ed. Blackwell Publishing, 1992. Reprinted with 
permission of Wolters Kluwer.)

140  Blackwell’s Five-Minute Veterinary Consult  
A
APCs may not cause hemodynamic abnormali -
ties; may be precursors of serious arrhythmias.
N/A
T reat CHF and correct any electrolyte or 
acid/base imbalances.
Dogs
• Digoxin (0.005–0.01 mg/kg PO q12h, 
maintenance dosage), diltiazem (0.5–1.5 mg/
kg PO q8h), or atenolol (0.25–1 mg/kg PO 
q12h) are used to treat clinically significant 
arrhythmias. • Digoxin—treatment of 
choice. • CHF is treated with appropriate 
dosage of diuretic, angiotensin-converting 
enzyme inhibitor, and pimobendan; approp  - 
riate management of CHF may reduce APC 
frequency.
Cats
• Cats with hypertrophic cardiomyopathy—
diltiazem (1–2.5 mg/kg PO q8h) or atenolol 
(6.25–12.5 mg PO q12–24h). • Cats 
with dilated cardiomyopathy—digoxin 
(one-fourth of a 0.125 mg digoxin tablet 
q24h or q48h).
Negative inotropic agents (e.g., propranolol) 
should be avoided in animals with CHF .
Use digoxin, diltiazem, atenolol, or propranolol 
cautiously in animals with underlying atrio-  
ventricular block or hypotension.POSSIBLE INTERACTIONS
N/A
N/A
  FOLLOW-UP
Monitor heart rate and rhythm with serial 
ECG.
N/A
Frequent APCs may further diminish cardiac 
output in patients with underlying heart 
disease and worsen clinical symptoms.
Even with optimal antiarrhythmic drug 
therapy, some animals have an increased 
frequency of APCs or deteriorate to more 
severe arrhythmia as the underlying disease 
progresses.
None
Typically occurs in geriatric dogs.
• Atrial extrasystoles. • Atrial premature 
contractions. • Atrial premature impulses. 
• Premature atrial complexes/contractions.
SEE ALSO
Supraventricular Tachycardia.
• APC = atrial premature complex. 
• CHF =  congestive heart failure.
Jackson BL, Lehmkuhl LB, Adin DB. Heart 
rate and arrhythmia frequency of normal 
cats compared to cats with asymptomatic 
hypertrophic cardiomyopathy. J Vet Cardiol 
2014, 16:215–225.
Tilley LP , Smith FWK Jr. Electrocardiography. 
Sleeper M, eds., Manual of Canine and 
Figure 2.
APCs in bigeminy in a cat under general anesthesia. The second complex of each pair is an APC and the first is a sinus complex. The abnormality in rhythm 
 disappeared after the anesthetic was stopped. (Source: From Tilley LP . Essentials of Canine and Feline Electrocardiography, 3rd ed. Baltimore: Williams & Wilkins, 
1992. Reprinted with permission of Wolters Kluwer.)Atrial Premature Complexes  (continued)

Canine and Feline, Seventh Edition  141
A
  BASICS
OVERVIEW
• Congenital defect in which interatrial septum 
fails to develop normally, resulting in communi -
cation between atria. Unknown cause; genetic 
basis suspected. Acquired atrial septal defects 
(ASD) secondary to atrial rupture reported with 
canine degenerative mitral valve disease. 
• Comprises 0.7–3.7% of congenital heart 
defects in dogs, <10% of congenital heart 
defects in cats. Significantly higher incidence 
(37.7%) noted in one study. • Three major 
types of ASD classified based on the location 
of the defect within the interatrial septum—
ostium primum ASD (most apical portion of 
septum, adjacent to the atrioventricular [AV] 
valves), ostium secundum ASD (central portion 
of the septum, region of fossa ovalis), and sinus 
venosus ASD (adjacent to cranial or caudal vena 
cava). • Secundum ASD with left-to-right 
shunting is most common (98.7% in one 
study of dogs and cats). • Ostium primum 
ASD typically large; possible component of AV 
canal defect. • Sinus venosus ASD typically 
located at junction of cranial vena cava (less 
commonly caudal vena cava) and right atrium. 
Right pulmonary veins may be directed at 
right atrium through the defect. May be 
associated with anomalous pulmonary venous 
connections of some/all pulmonary veins. 
• Isolated ASD typically shunts left to right. 
Magnitude of flow dependent on ASD size, 
relative systemic and pulmonary resistance, and 
relative ventricular compliance. Small restrictive 
defects allow atria to maintain normal differen -
tial pressure. Large defects may have significant 
left-to-right shunting, causing volume overload to 
right heart and pulmonary vessels. Secondary 
pulmonary hypertension can reverse shunting 
(i.e., right to left), termed Eisenmenger’s 
physiology. ASD with concurrent defects causing 
increased right atrial pressure (i.e., pulmonic 
stenosis, tricuspid valve dysplasia, tricuspid valve 
stenosis) may have balanced or reversed shunting.
• Dog and cat. • Various breeds affected; 
higher prevalence in boxer and standard 
poodle. • No sex predisposition.
SIGNS
• Typically asymptomatic (73.7% in one 
study). • Severe cases may show signs of 
congestive heart failure (CHF). • Generalized 
cyanosis possible with reversed shunting.
Clinical signs related to concurrent heart 
disease, CHF , or cyanosis; exercise intoler-
ance, syncope, and dyspnea.Physical Examination Findings
• Soft systolic murmur over left base due 
to increased blood flow across normal 
pulmonic valve. • Split S2 (fixed) due to 
delayed closure of pulmonic valve. 
• Cyanosis with right-to-left shunting. 
• Ascites and jugular vein distension 
with right CHF .
  DIAGNOSIS
• Typically normal. • Polycythemia with 
right-to-left shunting.
IMAGING
• None with small defects. • Right heart 
enlargement and vascular pattern (pulmonary 
overcirculation) with significant shunting.
Echocardiographic Findings
• Right atrial and/or right ventricular 
dilation. • Septal dropout (artifactual septal 
dropout is common and may lead to misdiag  - 
nosis). • Shunting across ASD by color-flow 
or spectral Doppler. • Increased pulmonic 
flow velocity. • Dilation of pulmonary trunk.
Electrocardiography
• Usually normal. • Right atrial and 
ventricular enlargement (tall P wave, deep 
S waves in lead II), right axis deviation. 
• Arrhythmias and intraventricular conduc-
tion disturbances possible.
  TREATMENT
GENERAL
• Long-term prognosis for small ASD is 
good; treatment typically unnecessary. 
• Large ASD with hemodynamically 
significant shunting and right-sided enlarge-
ment warrants closure.
MEDICAL THERAPY
• Standard treatment of CHF—furosemide, 
pimobendan, angiotensin-converting enzyme 
(ACE) inhibitor). • T reatment of poly-
cythemia (right-to-left shunting) if clinically 
SURGICAL THERAPY
• Open heart surgery under cardiopulmo -
nary bypass (surgical closure using patch 
graft). • Pulmonary artery banding as 
palliative measure to limit left-to-right 
shunting.CATHETER-BASED THERAPY
• Amplatzer® atrial septal occluder (ASO) 
device delivered percutaneously through jugular 
vein possible for some secundum-type defects. 
• Hybrid procedure involving surgical access 
and transatrial delivery of ASO device under 
inflow occlusion reported.
See Congestive Heart Failure, Left-Sided; 
Congestive Heart Failure, Right-Sided; and 
Hypertension, Pulmonary.
  FOLLOW-UP
• Periodic evaluation to assess cardiac 
structure and function. • Recheck when 
decompensation or other clinical signs 
develop.
• Dependent on ASD size and coexisting defects. 
• Small, isolated defects unlikely to cause 
clinical signs. • Defects >12 mm more likely 
to cause CHF .
SEE ALSO
• Congestive Heart Failure, Left-Sided. 
• Congestive Heart Failure, Right-Sided. 
• Hypertension, Pulmonary.
• ACE = angiotensin-converting enzyme. 
• ASD = atrial septal defect. 
• ASO = atrial septal occluder. 
Bonagura JD, Lehmkuhl LB. Congenital 
heart disease. In: Fox PR, Sisson D, Moïse 
ND, eds., Textbook of Canine and Feline 
Cardiology, 2nd ed. Philadelphia, PA: 
Saunders 1999, pp. 471–535.
Chetboul V, Charles V, Nicolle A, et al. 
Retrospective study of 156 atrial septal 
defects in dogs and cats (2001–2005). J Vet 
Med Assoc 2006, 53(4):179–184.
Author  Sandra P . Tou
Consulting Editor  Michael AherneAtrial Septal Defect

142  Blackwell’s Five-Minute Veterinary Consult  
A
  BASICS
ECG rhythm characterized by absence of P 
waves; condition can be temporary (e.g., 
associated with hyperkalemia or drug induced), 
terminal (e.g., associated with severe hyper -
kalemia or dying heart), or persistent.
Persistent Atrial Standstill
• P waves absent.
• Heart rate usually slow ( <60 bpm).
• Rhythm regular with supraventricular-type 
QRS complexes.
• Heart rate does not increase with atropine 
Hyperkalemic Atrial Standstill
• Heart rate normal or slow.
• Rhythm regular or irregular.
• QRS complexes tend to be wide and 
become wider as the potassium level rises; 
with severe hyperkalemia (potassium 
>10 mEq/L), the QRS complexes are replaced 
by a smooth biphasic curve.
• Heart rate may increase slightly with atropine.
Caused by an atrial muscular dystrophy/
cardiomyopathy; skeletal muscle involvement 
common.
Generally occurs with serum potassium levels 
>8.5 mEq/L; value influenced by serum 
sodium and calcium levels and acid-base status. 
Hyperkalemic patients with atrial standstill 
have sinus node function, but impulses do not 
activate atrial myocytes; thus, the associated 
rhythm is termed a sinoventricular rhythm. 
Since the sinus node is functional, an irregular 
rhythm may be due to sinus arrhythmia.
GENETICS
None
Rare rhythm disturbance.
None
Species
Persistent atrial standstill—most common in 
English springer spaniels; other breeds 
occasionally affected.Mean Age and Range
Most animals with persistent atrial standstill 
are young; animals with hypoadrenocorticism 
are usually young to middle-aged.
Hypoadrenocorticism more common in 
females (69%).
SIGNS
• Vary with underlying cause.
• Lethargy common; syncope may occur.
• Patients with persistent atrial standstill 
may show signs of congestive heart failure 
(CHF).
• Bradycardia common.
• Patients with persistent atrial standstill may 
have skeletal muscle wasting of the antebra -
chium and scapula.
CAUSES
• Atrial disease, often associated with 
atrial distension (e.g., cats with cardio  - 
myopathy).
• Atrial myopathy (persistent atrial 
standstill).
• Hyperkalemic atrial standstill.
• Hypoadrenocorticism.
• Conditions leading to obstruction or 
rupture of the urinary tract.
• Oliguric or anuric renal failure.
  DIAGNOSIS
• Slow atrial fibrillation.
• Sinus bradycardia with small or hidden 
P waves.
Normal
• Hyponatremia and sodium : potassium 
ratio <27 if atrial standstill secondary to 
• Azotemia and hyperphosphatemia 
with hypoadrenocorticism, renal failure, 
and rupture or obstruction of the urinary 
tract.
Adrenocorticotropic hormone (ACTH) 
stimulation test if hypoadrenocorticism 
suspected.IMAGING
Echocardiogram and electromyography if 
persistent atrial standstill suspected—  
cardiomegaly and depressed contractility may 
be seen.
Skeletal muscle biopsy in animals with 
persistent atrial standstill, particularly if 
skeletal muscle wasting noted.
• Greatly enlarged and paper-thin atria; usually 
biatrial involvement, although one case of only 
left atrial involvement was reported.
• Severe scapular and brachial muscle wasting 
in some dogs.
• Marked fibrosis, fibroelastosis, chronic 
mononuclear cell inflammation, and 
steatosis throughout the atria and interatrial 
septum.
  TREATMENT
Not life-threatening condition; animal can be 
treated as an outpatient.
Potentially life-threatening; often requires 
aggressive treatment.
Aggressive fluid therapy with 0.9% saline 
often required to correct hypovolemia 
and lower serum potassium levels (see 
Hyperkalemia) in patients with hyperkalemic 
atrial standstill.
ACTIVITY
Restrict activity in patients with persistent 
atrial standstill and signs of CHF or syncope.
DIET
N/A
Clinical signs generally improve after 
pacemaker implantation; signs of CHF 
may develop, and weakness and lethargy 
may persist even after heart rate and 
rhythm are corrected with the pacemaker.
Implant permanent ventricular pacemaker to 
regulate rate and rhythm.
Hyperkalemia secondary to urinary tract 
obstruction or rupture may require surgery.Atrial Standstill

Canine and Feline, Seventh Edition  143
A
T reat with standard therapy (pimobendan, 
diuretics, and angiotensin-converting enzyme 
(ACE) inhibitor, e.g., enalapril or benazepril) 
if CHF develops.
• T reat the underlying cause (e.g., oliguric 
renal failure, hypoadrenocorticism).
• Aggressive fluid therapy with 0.9% saline and 
possibly sodium bicarbonate or insulin with 
dextrose, as discussed under Hyperkalemia.
• Calcium gluconate—counters the cardiac 
effects of hyperkalemia; can be used in life- 
threatening situations while instituting 
treatment to lower potassium concentration.
Avoid potassium-containing fluids or 
medications that increase potassium 
concentration in hyperkalemic patients.
Diuretics lower preload and may worsen 
weakness in dogs with persistent atrial 
standstill and CHF unless a pacemaker has 
been implanted.
N/A
N/A
  FOLLOW-UP
• Monitor ECG during treatment of hyper  - 
kalemia and periodically in animals with a 
permanent ventricular pacemaker.• Monitor electrolytes in patients with 
hyperkalemic atrial standstill.
• Monitor patients with persistent atrial 
standstill for signs of CHF .
N/A
CHF in patients with persistent atrial 
standstill.
• Clinical signs generally improve after 
pacemaker implantation. Signs of CHF may 
develop, and weakness and lethargy may 
persist even after heart rate and rhythm are 
corrected with the pacemaker.
• Signs related to muscular dystrophy may 
persist.
• Median survival in 20 dogs with atrial 
standstill treated with a pacemaker was 866 days 
and was not influenced by breed or presence of 
heart failure at time of implantation.
Long-term prognosis is excellent if underlying 
cause can be corrected and hyperkalemia reversed.
Diseases causing hyperkalemia (e.g., hypo  - 
adrenocorticism, urethral obstruction or 
urinary tract tear, acidosis, and drugs).
Persistent atrial standstill—usually diagnosed 
in young animals; hypoadrenocorticism—
usually diagnosed in young to middle-aged 
animals.
NonePREGNANCY/FERTILITY/BREEDING
N/A
SYNONYMS
Silent atrium.
SEE ALSO
• Digoxin Toxicity.
• Hypoadrenocorticism (Addison’s Disease).
• ACE = angiotensin-converting enzyme.
Cervenec RM, Stauthammer CD, Fine DM, 
et al. Survival time with pacemaker 
implantation for dogs diagnosed with 
persistent atrial standstill. J Vet Cardiol 
2017, 19(3):240–246.
Kraus MS, Gelzer ARM, Moïse NS. 
T reatment of cardiac arrhythmias and 
conduction disturbances. In: Smith FWK, 
Tilley LP , Oyama MA, Sleeper MM, eds., 
Manual of Canine and Feline Cardiology, 
5th ed. St. Louis, MO: Saunders Elsevier, 
2016, pp. 313–329.
In: Smith FWK, Tilley LP , Oyama MA, 
Sleeper MM, eds., Manual of Canine and 
Saunders Elsevier, 2016, pp. 49–76.
Author  Francis W.K. Smith, Jr.
Figure 1 .
Atrial standstill in a dog with a potassium of 9 mEq/L. Note the absence of P waves and wide QRS complexes.(continued)  Atrial Standstill

144  Blackwell’s Five-Minute Veterinary Consult  
A
  BASICS
• Endocardial splitting is a linear defect 
limited to the atrial endocardium (typically 
left atrium [LA]) resulting from distension of 
the atrial wall beyond its elastic limits.
• Atrial tear results if the split extends 
through the myocardium and epicardium, 
resulting in a full-thickness atrial wall defect 
and hemorrhage into the pericardial space.
• Endocardial splitting typically results from 
increased LA pressure secondary to severe 
mitral regurgitation and mechanical trauma 
from the regurgitant jet; primary endocardial 
degeneration may also play a role.
• If split is incomplete, fibrin may seal the 
defect temporarily; either heals as a linear 
depression in endocardial surface or subse-
quently extends through myocardium, 
resulting in complete tear.
• LA tear results in peracute bleeding into 
pericardial sac and acute cardiac tamponade.
• If tear occurs in interatrial septum, an 
acquired atrial septal defect may form.
• Tearing of either atrium may also rarely occur 
secondary to blunt trauma, or iatrogenically during 
pericardiocentesis or cardiac catheterization.
GENETICS
Unknown
A rare cause of hemorrhagic pericardial 
effusion in the dog encompassing approxi-
mately 2% of pericardial effusion cases.
Species
Dog; uncommon in cat.
• Any breed predisposed to degenerative valve 
disease.
• If traumatic, any breed may be represented.
Middle-aged to older dogs.
Male dogs may be overrepresented.
SIGNS
• Acute weakness and collapse; may progress 
quickly to respiratory or cardiopulmonary arrest.
• History of chronic cardiac disease; signs of 
congestive heart failure (CHF) in most patients.
• Acute worsening of cough or dyspnea is 
commonly observed.
• Possible history of blunt trauma.Physical Examination Findings
• Collapse.
• Weak pulses or pulsus paradoxus.
• Pale, muddy, or ashen mucous membranes; 
prolonged capillary refill time (CRT).
• Other signs of significant cardiac disease 
(e.g., murmur, gallop sound, arrhythmia, 
cough, dyspnea) typically present.
• May have signs of right CHF (e.g., ascites, 
jugular venous distension).
• Heart sounds may be muffled, or if 
murmur was heard before atrial wall tear 
occurred, it may be reduced in intensity.
CAUSES
• Myxomatous mitral valve disease.
• Chordae tendineae rupture.
• Chest trauma.
• Cardiac catheterization.
• Severe mitral regurgitation; LA enlargement.
• May be precipitated by excitement, stress, 
or activity.
  DIAGNOSIS
• Other causes of acute cardiovascular 
collapse or syncope.
• Pericardial effusion from other causes 
(e.g., neoplastic, idiopathic).
• CHF .
• Severe arrhythmias.
• Elevations in serum lactate; metabolic 
acidosis.
• Increased alanine aminotransferase/
aspartate aminotransferase in some patients.
• Prerenal azotemia; hyponatremia or other 
electrolyte derangements may be seen.
NT-proBNP and cardiac troponin I (cTnI) 
levels may be elevated.
IMAGING
• Usually moderate to severe LA enlargement; 
cardiac silhouette may be rounded and 
further enlarged compared with previous 
• Interstitial to alveolar pulmonary infiltrates 
if left-sided CHF present.
• Pleural effusion, ascites, hepatomegaly, and 
large caudal vena cava if right-sided CHF .
ECG
• Pericardial effusion—volume may be 
relatively small as pericardium remains 
inelastic due to acute nature of bleed; 
characteristic linear, hyperechoic thrombus 
may be seen within pericardial sac.• Actual tear often not identified, though 
associated thrombus occasionally visualized 
within LA.
• Evidence of cardiac tamponade.
• Signs of advanced myxomatous mitral valve 
disease with moderate to severe LA enlarge-
ment expected.
ECG
• Sinus tachycardia.
• Atrial or ventricular arrhythmias.
• Possible dampened QRS complexes.
• Electrical alternans.
• ST-segment abnormalities.
• Possible left ventricular or LA enlargement 
pattern.
• Endocardial splitting is noted grossly as 
pale linear depression in atrial endocardium.
• Atrial wall tears appear as full-thickness 
defects extending through atrial endocar-
dium, myocardium, and epicardium; 
associated thrombus may or may not be 
present. Caudolateral aspect of LA most 
commonly affected, with many tears 
occurring at atrio-auricular junction.
• Hemorrhagic pericardial effusion or peri  - 
cardial thrombus with acute tears.
• Myxomatous valve disease characterized by 
thickened leaflets with rolled edges; may have 
chordae tendineae rupture; possibly atrial jet 
lesions.
• Cardiomegaly with severe LA enlargement 
expected.
  TREATMENT
• If LA tear suspected, perform pericardio-
centesis only if effusion causing symptomatic, 
life-threatening cardiac tamponade, since 
further hemorrhage into pericardial sac or 
exsanguination may occur once pericardial 
fluid removed; remove only enough fluid to 
improve clinical signs.
• Pericardiocentesis likely difficult given small 
volume of effusion typically present, severe 
cardiomegaly, and small size of most dogs 
with LA rupture; ultrasound guidance and 
continuous ECG monitoring highly 
• Best practices for management of LA tear have 
not been clearly established; however, aggressive 
medical management to lower LA pressure using 
afterload and preload reducers recommended 
based on author’s clinical experience.
• If fibrin clot forms over defect, patient may 
stabilize and recover.
• Administer oxygen to dyspneic or hemody-
namically unstable dogs.Atrial Wall Tear

Canine and Feline, Seventh Edition  145
A
• Administer IV fluids only if evidence of 
hypovolemia present; most dogs volume 
overloaded and further intravascular volume 
expansion will increase LA pressure and 
potentially worsen tamponade.
ACTIVITY
Strict cage rest in acute period, followed by 
chronic exercise restriction.
DIET
Sodium restriction may be indicated for 
animals with advanced myxomatous valve 
disease with cardiomegaly.
LA tear typically accompanies advanced 
cardiac disease and chronic medical therapy is 
necessary; though prognosis is guarded for 
surviving acute event, some dogs have lived 
more than a year after the incident.
Exploratory thoracotomy may be considered 
if hemorrhage persists or recurs, but should 
be undertaken cautiously given advanced state 
of cardiac disease typically present.
• Atrial tears occur secondary to elevated LA 
pressure; thus medical therapy should be 
focused on lowering LA pressures to reduce 
continued hemorrhage into pericardial space 
and permit fibrin clot formation at the tear; 
this may be accomplished with preload (e.g., 
diuretics, nitroglycerin paste) and/or afterload 
reducers (arterial vasodilators).
• Preload and afterload reduction must be 
undertaken cautiously to avoid worsening of 
hemodynamic compromise.
• If concurrent CHF present, afterload 
reduction may be achieved by conservative 
doses of sodium nitroprusside; low starting CRI 
dose of 0.5–1  μg/kg/min recommended to 
decrease LA pressure without precipitating 
significant hypotension; dose may be uptitrated 
as necessary every 15–30 min up to maximum 
of 10  μg/kg/min to improve clinical signs and/
or reduce blood pressure by 10–15 mmHg.
• Alternatively, amlodipine may be started at 
0.1–0.2 mg/kg PO q24h; chronic amlodipine 
therapy may be implemented in normoten-
sive or hypertensive animals to reduce regurg  - 
itant fraction and lower LA pressure.
• Cautious diuretic use, if needed, to treat 
dyspnea associated with concomitant CHF 
(e.g., 1–2 mg/kg furosemide IV as needed); 
signs of left-sided CHF may worsen as cardiac 
tamponade resolves due to augmented preload—  
more aggressive diuretic therapy may then be 
required.• Pimobendan (0.25–0.3 mg/kg PO q12h) 
may result in further LA pressure reduction, 
though studies have not specifically examined 
its use in setting of LA rupture.
• Once patient is stable, angiotensin-  
converting enzyme inhibitors (e.g.,  enalapril 
0.5 mg/kg q12–24h) should be implemented 
for chronic management of accompanying 
CHF .
• Antithrombotic medications.
• Arterial vasodilators, if significant hypoten-
sion present.
• Aggressive fluid therapy unwarranted; 
further volume expansion may increase LA 
pressure, worsen cardiac tamponade, and 
contribute to hemodynamic compromise.
• Best practices for management of LA tear 
not clearly established; choice of whether to 
perform pericardiocentesis, and whether to 
administer preload and/or afterload reducers, 
should be based on assessment of volume 
status, blood pressure, and clinical stability of 
patient.
Sodium nitroprusside should not be admin  - 
istered concurrently with phosphodiesterase-
V inhibitors (e.g., sildenafil, tadalafil) due to 
potential for life-threatening systemic 
N/A
  FOLLOW-UP
• Recommend close monitoring of respira-
tory rate and effort, mucous membrane color 
and CRT, pulse quality, and heart rate; blood 
pressure monitoring recommended if arterial 
vasodilators are implemented.
• Follow-up examination with echocardiog -
raphy helps determine resolution of pericardial 
effusion and resorption of atrial or pericar -
dial clot.
• Close follow-up every 2–3 months thereafter 
recommended for repeat pericardial fluid 
checks and medication adjustments as 
Avoid strenuous physical activity and 
excitement.
• Even if the tear seals, patient is prone to further 
tears because of underlying cardiac disease.
• Most dogs have or will develop concurrent 
CHF .EXPECTED COURSE AND PROGNOSIS
Prognosis is guarded; however, some animals can 
do well for several months or more with exercise 
restriction and optimal medical management.
• CHF .
• Mainstem bronchial compression.
Middle-aged to older dogs are predisposed.
N/A
N/A
SYNONYMS
• Atrial rupture.
• Atrial splitting.
SEE ALSO
• Atrial Septal Defect.
• Congestive Heart Failure, Left-Sided.
• Myxomatous Mitral Valve Disease.
• Pericardial Disease.
• Syncope.
• CRT = capillary refill time.
• cTnI = cardiac troponin I.
• LA = left atrium/atrial.
James Buchanan Cardiology Library: https://
www.vin.com/apputil/content/defaultadv1.
aspx?pId=84
Nakamura RK, Tompkins E, Russell NJ, et al. 
Left atrial rupture secondary to myxoma-
tous mitral valve disease in 11 dogs. J Am 
Anim Hosp Assoc 2014, 50:405–408.
Peddle GD, Buchanan JW. Acquired atrial 
septal defects secondary to rupture of the 
atrial septum in dogs with degenerative 
mitral valve disease. J Vet Cardiol 2010, 
12:129–134.
Reineke EL, Burkett DE, Drobatz KJ. Left 
atrial rupture in dogs: 14 cases (1990–2005). 
J Vet Emerg Crit Care 2008, 18:158–164.
Author  Suzanne M. Cunningham
Consulting Editor  Michael Aherne(continued)  Atrial Wall Tear

146  Blackwell’s Five-Minute Veterinary Consult  
A
  BASICS
• All atrial impulses are blocked at the 
atrioventricular (AV) junction; atria and 
ventricles beat independently. A secondary 
“escape” pacemaker site (junctional or 
ventricular) stimulates the ventricles. • Atrial 
rate normal. • Idioventricular escape rhythm 
slow.
• Ventricular rate slower than atrial rate 
(more P waves than QRS complexes)—  
ventricular escape rhythm (idioventricular) 
usually <40 bpm; junctional escape rhythm 
(idiojunctional) 40–60 bpm in dogs and 
60–100 bpm in cats. • P waves—usually 
normal configuration (Figures 1 and 2). 
• QRS complex—wide and bizarre when 
pacemaker located in the ventricle, or in the 
lower AV junction in a patient with bundle 
branch block; normal when escape  pacemaker 
in the lower AV junction (above the 
bifurcation of the bundle of His) in a patient 
without bundle branch block. • No 
conduction between the atria and the 
ventricles; P waves have no constant relation  - 
ship with QRS complexes; P–P and R–R 
intervals relatively constant (except for a sinus 
arrhythmia).
Slow ventricular escape rhythms ( <40 bpm) 
result in low cardiac output and eventual 
heart failure, often when animal is excited or 
exercised, since demand for greater cardiac 
output is not satisfied. As the heart fails, signs 
increase with mild activity.
GENETICS
Can be an isolated congenital defect.INCIDENCE/PREVALENCE
N/A
Species
• Cocker spaniel—can have idiopathic fibrosis. 
• Pug and Doberman pinscher—can have 
associated sudden death, AV conduction 
defects, and bundle of His lesions.
Geriatric animals, except congenital heart 
disease patients. Median age for cats— 
14 years.
Intact female dogs.
SIGNS
• Exercise intolerance. • Weakness or 
syncope. • Occasionally, congestive heart 
failure (CHF).
• Bradycardia. • Variable third and fourth 
heart sounds. • Variation in intensity of first 
heart sounds. • Signs of CHF possible. 
• Intermittent “cannon” A waves in jugular 
venous pulses. • Often bounding arterial 
pulses.
• Isolated congenital defect. • Idiopathic 
fibrosis. • Infiltrative cardiomyopathy 
(amyloidosis or neoplasia). • Hypertrophic 
cardiomyopathy in cats. • Digitalis toxicity.
• Hyperthyroidism in cats. • Myocarditis.
• Endocarditis. • Electrolyte disorder.
• Myocardial infarction. • Other congenital 
heart defects. • Lyme disease. • Chagas 
disease.  DIAGNOSIS
• Advanced second-degree AV block. • Atrial 
standstill. • Accelerated idioventricular 
rhythm.
• Abnormal serum electrolytes (e.g., hyper  - 
kalemia, hypokalemia) possible. • High white 
blood cell count with left shift in animals 
with bacterial endocarditis.
• High serum digoxin concentration if AV 
block due to digoxin toxicity. • Lyme titer 
and accompanying clinical signs if AV block 
due to Lyme disease.
IMAGING
Echocardiography and Doppler ultrasound  
to assess cardiac structure and function.
• Electrocardiography. • His bundle electro -
gram to determine the site of the AV block is 
possible. • Long-term (Holter) ambulatory 
recording if AV block is intermittent.
Degeneration or fibrosis of the AV node  
and its bundle branches, associated with 
endocardial and myocardial fibrosis and 
organized endomyocarditis.
  TREATMENT
• Temporary or permanent cardiac 
 pacemaker—only effective treatment in 
symptomatic patients. • Carefully monitor 
asymptomatic patients without a pacemaker 
for development of clinical signs.Atrioventricular Block, Complete (Third Degree)
Figure 1 .
Complete heart block in a dog. The P waves occur at a rate of 120, independent of the ventricular rate of 50. The QRS configuration is a right bundle branch block 
pattern. (Source: From Tilley LP . Essentials of Canine and Feline Electrocardiography, 3rd ed. Baltimore: Williams & Wilkins, 1992. Reprinted with permission of 
Wolters Kluwer.)

Canine and Feline, Seventh Edition  147
A
Cage rest prior to pacemaker implantation; 
when the pulse generator is implanted into a 
subcutaneous pocket, a nonconstricting 
bandage is placed around the ventral neck or 
abdomen for 3–5 days to prevent seroma 
formation or pacemaker movement.
ACTIVITY
DIET
No modifications unless required to manage 
underlying condition (e.g., low-salt diet).
symptomatic patients. • Asymptomatic 
patients without a pacemaker—must be 
carefully monitored for development of 
• Most patients—at high anesthetic 
cardiopulmonary risk; usually paced 
preoperatively with a temporary external 
pacemaker system. • The small size of cats 
makes pacemaker implantation more 
difficult than in dogs.
• T reatment with drugs—usually of no 
value. T raditionally used to treat complete 
AV block: atropine, isoproterenol, cortico -
steroids, and dobutamine. • Intravenous 
isoproterenol infusion may help increase the 
rate of the ventricular escape rhythm to stabilize hemodynamics. • If CHF—diuretic 
and vasodilator therapy may be needed 
before pacemaker implantation.
Avoid digoxin, xylazine, acepromazine, beta 
blockers (e.g., propranolol and atenolol), and 
calcium channel blockers (e.g., verapamil and 
diltiazem); ventricular antiarrhythmic agents 
are dangerous because they suppress lower 
escape foci.
Vasodilators—may cause hypotension in 
animals with complete AV block; monitor 
closely if used, especially prior to pacemaker 
implantation.
  FOLLOW-UP
• Monitor—pacemaker function with serial 
electrocardiograms. • Radiographs—  following 
pacemaker implantation, to confirm the 
position of the lead and generator.
N/A
Pulse generators—pacemaker replacement 
necessary if battery becomes depleted, pulse 
generator malfunction occurs, or exit block 
develops; pacemaker leads can become 
dislodged and infected.
Poor long-term prognosis if no cardiac pace  - 
maker implanted, especially when the animal has 
clinical signs. Cats can sometimes survive >1 
year without a permanent pacemaker.  MISCELLANEOUS
None
Kellum HB, Stepien RL. Third-degree 
atrioventricular block in 21 cats (1997–2004). 
J Vet Intern Med 2006, 20:97–103.
Schrope DP , Kelch WJ. Signalment, clinical 
signs, and prognostic indicators associated 
with high-grade second or third-degree 
atrioventricular block in dogs: 124 cases 
(January 1, 1997–December 31, 1997). 
J Am Vet Med Assoc 2006, 
228:1710–1717.
In Smith FWK, Tilley LP , Oyama M, 
Figure 2.
Complete heart block in a cat. The P wave rate is 240/minute, independent of the ventricular rate of 48/minute. QRS configuration is a left bundle branch block 
Wolters Kluwer.)(continued)  Atrioventricular Block, Complete (Third Degree)

148  Blackwell’s Five-Minute Veterinary Consult  
AAtrioventricular Block, First Degree
  BASICS
Refers to a delay in conduction that occurs 
between atrial and ventricular activation.
• Rate and rhythm—usually normal.
• Usually there are regularly occurring 
normal P waves and QRS complexes 
(Figures 1 and 2).
• Prolonged, consistent PR intervals—
dogs, >0.13 sec; cats, >0.09 sec (Figures 1 
and 2).
• Virtually never causes clinical signs.
• May become a more severe atrioventricular 
(AV) conduction disturbance in some animals.
• Normally the PR interval tends to shorten 
with rapid heart rates.
• May be the result of intra-atrial conduction 
delay (prolongation of the PA interval on 
surface ECG and simultaneous His bundle 
electrogram) or delay of conduction within 
the AV node itself (prolongation of the AH 
interval on His bundle electrogram).
GENETICS
N/A
Common
None
Species
Dog and cat.Breed Predilections
American cocker spaniel, dachshund, 
brachycephalic dogs, Persian cats.
• May occur in young, otherwise healthy 
dogs as a manifestation of high vagal tone.
• Intra-atrial conduction delay involving 
the right atrium may be seen with 
congenital heart disease, especially AV 
septal defects.
• May be noted in aged patients with 
degenerative conduction system  disease, 
particularly cocker spaniels and 
dachshunds.
• Persian cats of any age with high vagal tone 
and in cats of any age with hypertrophic 
cardiomyopathy.
SIGNS
• Most animals are asymptomatic.
• If drug induced, may have a history of 
clinical signs related to drug toxicity—anorexia, 
vomiting, and diarrhea with digoxin; weakness 
with calcium channel blockers or β-adrenergic 
antagonists.
Normal—unless also signs of more general-
ized myocardial disease, drug toxicity, or 
noncardiac disease.
CAUSES
• May occur in normal animals.
• Enhanced vagal stimulation resulting from 
noncardiac diseases—usually accompanied by 
sinus arrhythmia, sinus arrest, and/or Mobitz 
type I second-degree AV block.
• Pharmacologic agents—e.g., digoxin, 
β-adrenergic antagonists, calcium channel 
blocking agents, propafenone, amiodarone, 
α2-adrenergic agonists, parasympathomimetic agents (bethanechol, physostigmine, 
pilocarpine), and severe procainamide or 
quinidine toxicity.
• Degenerative disease of the conduction 
system.
• Hypertrophic cardiomyopathy.
• Myocarditis (especially Trypanosoma cruzi , 
Borrelia burgdorferi , Rickettsia rickettsii ).
• Infiltrative diseases (tumors, amyloid).
• Atropine administered intravenously may 
briefly prolong the PR interval.
Any condition or intervention that raises 
vagal tone.
  DIAGNOSIS
P waves superimposed upon preceding 
T waves because of first-degree AV block 
should be differentiated from bifid T waves.
• Serum electrolytes—hypokalemia and 
hyperkalemia may predispose to AV 
conduction disturbances.
• Leukocytosis—may be noted with bacterial 
endocarditis or myocarditis.
• Serum digoxin concentration—may be high.
• T. cruzi , B. burgdorferi , R. rickettsii  titers— 
may be high.
• Thyroxine (T4)—may be high in cats if 
associated with thyrotoxic myocardial disease.
IMAGING
Echocardiographic examination—may reveal 
hypertrophic or infiltrative myocardial 
disorder.
Figure 1 .
Lead II ECG rhythm strip recorded from a cat with hypertrophic cardiomyopathy. There is sinus bradycardia (120 bpm) and first-degree AV conduction block. 
The PR interval is 0.12 second (paper speed = 50 mm/s).

Canine and Feline, Seventh Edition  149
A
May be needed to identify causes of high 
vagal tone—upper airway disease, cervical 
and thoracic masses, gastrointestinal 
disorders, and high intraocular pressure.
Variable—depend on underlying cause.
  TREATMENT
• Remove or treat underlying cause(s).
• Hospitalization may be necessary to manage 
the underlying cause (e.g., cardiomyopathy, 
gastrointestinal disease, airway disease).
N/A
ACTIVITY
Unrestricted; unless restriction required for an 
underlying condition.
DIET
No modifications or restrictions, unless 
required to manage an underlying condition.
Generally unnecessary.
None, unless required to manage an under  - 
lying condition.
Medications used only if needed to manage 
an underlying condition.
• Avoid hypokalemia—increases sensitivity 
to vagal tone; may potentiate AV conduction 
delay.• Avoid drugs likely to impair impulse 
conduction further (calcium channel blocking 
agents, β-adrenergic antagonists, α2-adrenergic 
agonists, amiodarone, propafenone).
Drugs with vagomimetic action (e.g., digoxin, 
bethanechol, physostigmine, pilocarpine) may 
potentiate first-degree block.
N/A
N/A
  FOLLOW-UP
Except in healthy young animals, monitor 
ECG to detect any progression in conduction 
disturbance.
N/A
N/A
• Depends on underlying cause.
• Prognosis usually excellent if no significant 
underlying disease is present.
None
PR interval—tends to lengthen with 
advancing age.
N/A
SEE ALSO
• Atrioventricular Block, Complete 
(Third Degree).
• Atrioventricular Block, Second Degree—
Mobitz Type I.
Mobitz Type II.
• AV = atrioventricular
• T4 = thyroxine
Berger MG, Rubenstein JC, Roth JA. Cardiac 
arrhythmias. In: Benjamin IJ, Griggs RC, 
Wing EJ, Fitz JG, eds., Andreoli and 
Carpenter’s Cecil Essentials of Medicine, 
9th ed. Philadelphia, PA: Saunders, 2016, 
pp. 110–135.
Miller MS, Tilley LP , Smith FWK, Fox PR. 
Electrocardiography. In: Fox PR, Sisson D, 
Moïse NS, eds., Textbook of Canine and 
Feline Cardiology. Philadelphia, PA: 
Saunders, 1999, pp. 67–106.
Santilli R, Moïse NS, Pariaut R, Perego M. 
Authors  Francis W.K. Smith, Jr. and Larry P . 
Tilley
Figure 2.
Lead II ECG rhythm strip recorded from a dog showing sinus tachycardia (175 bpm) and first-degree AV conduction block. Because the heart rate is rapid, P waves 
are superimposed on the downslope of the preceding T waves. The PR interval exceeds 0.16 second (paper speed = 50 mm/s).(continued)  Atrioventricular Block, First Degree

150  Blackwell’s Five-Minute Veterinary Consult  
AAtrioventricular Block, Second Degree—Mobitz Type I
  BASICS
Second-degree atrioventricular (AV) block 
refers to failure of one or more P waves but 
not all P waves to be conducted. Mobitz type 
I second-degree AV block occurs when AV 
transmission is progressively delayed prior to 
a blocked P wave.
• PR interval—becomes progressively 
longer prior to the appearance of a P wave 
that is not followed by a QRS complex 
(Figure 1).
• Heart rate and QRS morphology—usually 
normal.
• Often cyclic.
• Frequently associated with high resting 
vagal tone and sinus arrhythmia in dogs.
• Generally not pathologic or hemodynami-
cally significant.
• This type of AV block usually results 
from conduction delay within the AV 
node itself (rather than delay in other 
segments of the AV conducting system) and 
is characterized by a progressive increase in 
AH interval, with eventual block between 
the A and H deflections on a His bundle 
recording.
GENETICS
N/A
Radiotelemetry studies have shown that this 
arrhythmia occurs in 64% of healthy adult 
dogs and 100% of healthy puppies 8–12 
weeks of age.
Species
N/A
• Usually occurs in young, otherwise healthy 
• Occasionally occurs in older dogs with 
abnormally strong vagal tone.
• Rarely noted in old dogs with degenerative 
conduction system disease.
SIGNS
• If drug induced, owner may report signs of 
drug toxicity—anorexia, vomiting, and 
diarrhea with digoxin; weakness with calcium 
channel blockers or β-adrenergic antagonists.
• If heart rate is abnormally slow, syncope or 
weakness may occur.
• May be normal unless signs of more 
generalized myocardial disease or noncardiac 
disease are present.
• Intermittent pauses in the cardiac rhythm.
• First heart sound may become progressively 
softer, followed by a pause.
• An audible S4 may be heard unaccompa-
nied by S1 and S2 when block occurs.
CAUSES
• Occasionally noted in normal animals.
sinus arrhythmia, sinus arrest.
• Pharmacologic agents—digoxin, β-adrenergic 
antagonists, calcium channel blocking agents, 
propafenone, amiodarone, α2-adrenergic 
agonists, opioids.
Any condition or intervention that enhances 
vagal tone.  DIAGNOSIS
• Nonconducted P waves from supraventricu -
lar premature impulses or supraventricular 
tachycardias should be distinguished from 
second-degree AV block.
• Type II second-degree AV block (no 
variation in PR intervals).
Hypokalemia may predispose to AV 
Serum digoxin concentration—may be high.
IMAGING
N/A
• May be necessary to identify specific 
causes of enhanced vagal tone (e.g., upper 
airway disease, cervical and thoracic masses, 
gastrointestinal disorders, and high intraocu-
lar pressure).
• Atropine response test—administer 
0.04 mg/kg atropine IM and repeat ECG in 
20–30 minutes; may be used to determine 
whether AV block is due to vagal tone; 
resolution of AV block with atropine 
supports vagal cause.
• Electrophysiologic studies are generally 
unnecessary, but will confirm this type of 
second-degree AV block if surface ECG is 
equivocal.
Generally, no gross or histopathologic findings.
  TREATMENT
• T reatment usually unnecessary.
• T reat or remove underlying cause(s).
Figure 1 .
Lead II ECG strip recorded from a dog with Mobitz type I, second-degree AV block. The PR intervals become progressively longer, with the longest PR intervals 
preceding nonconducted P waves (typical Wenckebach phenomenon) (paper speed = 50 mm/s).

Canine and Feline, Seventh Edition  151
A
ACTIVITY
Unrestricted
DIET
Modifications or restrictions only to manage 
Explain that any treatment is directed 
toward reversing or eliminating an under -
lying cause.
N/A except to manage an underlying 
condition.
Only as needed to manage an underlying 
potentiate block.
Hypokalemia increases the sensitivity to vagal 
tone and may potentiate AV conduction delay.
Typically not necessary.
N/A
N/A
N/A
N/A
N/A
SYNONYMS
• Wenckebach block.
• Wenckebach periodicity.
• Wenckebach phenomenon.
SEE ALSO
• Atrioventricular Block, First Degree.
Mobitz Type II.ABBREVIATIONS
• AV = atrioventricular.
Branch CE, Robertson BT, Williams JC. 
Frequency of second-degree atrioventricular 
heart block in dogs. Am J Vet Res 1975, 
36:925–929.
Kittleson MD. Electrocardiography. In: 
Kittleson MD, Kienle RD, eds., Small 
Animal Cardiovascular Medicine. St. Louis, 
MO: Mosby, 1998, pp. 72–94.
Tilley
available online(continued)  Atrioventricular Block, Second Degree—Mobitz Type I

152  Blackwell’s Five-Minute Veterinary Consult  
AAtrioventricular Block, Second Degree—Mobitz Type II
  BASICS
refers to failure of one or more P waves, but 
not all P waves, to be conducted. Mobitz type 
II second-degree AV block occurs when one or 
more P waves are blocked without a preceding 
progressive delay in AV transmission.
• One or more P waves not followed by a 
QRS complex; PR interval is constant, but 
may be either normal or consistently 
prolonged (Figure 1).
• Ventricular rate—usually slow.
• Fixed ratio of P waves to QRS complexes 
may occur (e.g., 2 : 1, 3 : 1, 4 : 1 AV block).
• High-grade (advanced) second-degree AV 
block is characterized by two or more 
consecutively blocked P waves.
• In second-degree AV block with a 2 : 1 con -
duction ratio or higher, it is impossible to 
observe prolongation of the PR interval before 
the block, so a designation of Mobitz type I 
vs. II is not appropriate.
• QRS complexes may appear normal, but 
may also be wide or have an abnormal 
morphology due to aberrant intraventricular 
conduction or ventricular enlargement.
• Abnormally wide QRS complexes may 
indicate serious, extensive cardiac disease.
• Rare in healthy animals.
• May be hemodynamically important when 
ventricular rate is abnormally slow.
• May progress to complete AV block, parti  - 
cularly when accompanied by wide QRS 
• Typically this type of AV block results from 
conduction delay within the AV node itself 
(rather than delay in another segment of the 
AV conducting system) that is characterized 
by normal or prolonged AH intervals, with 
intermittent block between A and H deflec- 
tions on a His bundle electrogram.SYSTEMS AFFECTED
• Central nervous or musculoskeletal systems 
if inadequate cardiac output.
GENETICS
May be heritable in pugs.
Unknown
N/A
Species
American cocker spaniel, pug, dachshund, 
Airedale terrier, Doberman pinscher.
Generally occurs in older animals.
N/A
SIGNS
• Presenting complaint may be syncope, 
collapse, weakness, or lethargy.
• Some animals are asymptomatic.
• Animals may show signs of the underlying 
disease process if present.
• ± weakness.
• May be intermittent pauses in the cardiac 
rhythm.
• An S4 may be audible in lieu of the normally 
expected heart sounds (i.e., S1, S2) when the 
block occurs.
• If associated with digoxin intoxication, there 
may be vomiting, anorexia, and diarrhea.
• May be other abnormalities reflecting the 
underlying etiology.
CAUSES
• Heritable in pugs.
• Enhanced vagal stimulation from noncardiac 
diseases.• Degenerative change within the cardiac 
conduction system—replacement of AV 
nodal cells and/or Purkinje fibers by 
fibrotic and adipose tissue in old cats 
and dogs.
• Pharmacologic agents (e.g., digoxin, 
blocking agents, propafenone, α2-adrenergic 
agonists, muscarinic cholinergic agonists, 
or severe procainamide or quinidine 
toxicity).
• Infiltrative myocardial disorders (neoplasia, 
amyloid).
• Endocarditis (particularly involving the 
aortic valve).
• Myocarditis (viral, bacterial, parasitic, 
idiopathic).
• Cardiomyopathy (especially in cats).
• T rauma.
cause a brief period of first- or second-degree 
heart block before increasing the heart rate.
  DIAGNOSIS
• High-grade (advanced) form must be 
distinguished from complete AV block.
• Nonconducted P waves arising from 
refractoriness of the conduction system 
during supraventricular tachycardias must 
be differentiated from pathologic conduction 
block.
hyperkalemia may predispose to AV.
• Conduction disturbances.
• Electrolyte abnormalities (e.g., severe 
hypokalemia, hyperkalemia, or hypercalce-
mia) may predispose to AV block.
Figure 1 .
Lead II ECG rhythm strip recorded from a dog with both first- and second-degree AV block. The second-degree AV block is high grade, with both 2 : 1 and 3 : 1 
block resulting in variation in the RR intervals. The PR interval for the conducted beats is prolonged but constant (0.28 second) (paper speed = 25 mm/s).

Canine and Feline, Seventh Edition  153
A
• High thyroxine (T4) in cats—if associated 
with hyperthyroidism.
• High arterial blood pressure—if associated 
with hypertensive heart disease.
• Positive Borrelia , Rickettsia , or Trypanosoma 
cruzi titers—if associated with one of these 
infectious agents.
• Blood cultures may be positive in patients 
with vegetative endocarditis.
IMAGING
Echocardiographic examination may reveal 
structural heart disease (e.g., endocarditis, 
neoplasia, or cardiomyopathy).
whether AV block is due to high vagal tone.
• Electrophysiologic testing is generally 
unnecessary, but can be done to confirm this 
type of AV block if surface ECG findings are 
• Variable—depend on underlying cause.
• Old animals with degenerative change of 
the conduction system may have focal 
mineralization of the interventricular septal 
crest visible grossly; chondroid metaplasia of 
the central fibrous body and increased fibrous 
connective tissue in the AV bundle is noted 
histopathologically.
  TREATMENT
• T reatment—may be unnecessary if heart 
rate maintains adequate cardiac output.
• Positive dromotropic interventions are 
indicated for symptomatic patients.
ACTIVITY
Cage rest advised for symptomatic patients.
DIET
• Need to seek and specifically treat under- 
lying cause.• Pharmacologic agents may not be effective 
long term.
Permanent pacemaker may be required for 
long-term management of symptomatic patients.
• Atropine (0.02–0.04 mg/kg IV/IM) or 
glycopyrrolate (5–10  μg/kg IV/IM) may be 
used short term if positive atropine response.
• Chronic anticholinergic therapy (propan-
theline 0.5–2 mg/kg PO q8–12h or 
hyoscyamine 3–6  μg/kg q8h)—indicated for 
symptomatic patients if improved AV 
conduction with atropine response test.
• Isoproterenol (0.04–0.09  μg/kg/min IV to 
effect) or dopamine (2–5  μg/kg/min IV to 
effect) may be administered in acute, life-
threatening situations to enhance AV conduc -
tion and/or accelerate an escape focus.
• Drugs with vagomimetic action (e.g., 
digoxin, bethanechol, physostigmine, 
pilocarpine) may potentiate block.
• Avoid drugs likely to impair impulse 
conduction further or depress a ventricular 
escape focus (e.g., procainamide, quinidine, 
lidocaine, calcium channel blocking agents, 
β-adrenergic blocking agents).
Hypokalemia—increases sensitivity to vagal 
N/A
N/A
  FOLLOW-UP
Periodic ECG because risk of progression to 
complete (third-degree) AV block.
N/A
Prolonged bradycardia may cause secondary 
congestive heart failure or inadequate renal 
perfusion.EXPECTED COURSE AND PROGNOSIS
Variable—depends on cause. If degenerative 
disease of the cardiac conduction system, 
often progresses to complete (third-degree) 
AV block.
May be noted in cats with primary or 
secondary myocardial disease.
N/A
N/A
N/A
SEE ALSO
• Atrioventricular Block, Complete (Third 
Degree).
Authors  Larry P . Tilley and Francis W.K. 
Smith, Jr.
Consulting Editors  Michael Aherne
available online(continued)  Atrioventricular Block, Second Degree—Mobitz Type II

154  Blackwell’s Five-Minute Veterinary Consult  
A
Atrioventricular Valve Dysplasia
  BASICS
A congenital malformation of the mitral or 
tricuspid valve apparatus.
• Atrioventricular valve dysplasia (AVVD) 
can result in valvular insufficiency, valvular 
stenosis, or dynamic outflow tract obstruc-
tion, depending on the anatomic abnormality. 
AVVD may occur alone or in association with 
abnormalities of the ipsilateral outflow tract 
(e.g., valvular or subvalvular aortic or pulmonic 
stenosis). It is not uncommon for mitral and 
tricuspid valve dysplasia to occur together in 
the same patient.
• Valvular insufficiency results in ipsilateral atrial 
dilation, eccentric hypertrophy of the associated 
ventricle, and, if severe, signs of congestive heart 
failure (CHF). Cardiomyopathy of chronic 
volume overload and elevated atrial pressures are 
the end result, culminating in pulmonary 
congestion (with mitral valve dysplasia [MVD]) 
or systemic congestion (with tricuspid valve 
dysplasia [TVD]).
• Valvular stenosis results in atrial dilation 
and hypertrophy and, if severe, hypoplasia of 
the receiving ventricle. The end result is atrial 
pressure elevation, also resulting in pulmo-
nary congestion (mitral stenosis) or systemic 
congestion (tricuspid stenosis). Right-to-left 
shunting may occur in cases of tricuspid 
stenosis if there is an atrial septal defect or 
patent foramen ovale. Pulmonary hyperten-
sion is a common complication in animals 
with mitral valve stenosis.
• Dynamic outflow tract obstruction may 
occur in patients with MVD, with resultant 
concentric left ventricular (LV) hypertrophy 
that is proportional to the severity of the 
• Ebstein’s anomaly is a rare form of TVD, 
characterized by apical displacement of the 
basal tricuspid leaflet attachments and 
resultant right atrial (RA) enlargement, with a 
small right ventricle (“atrialized” right 
ventricle). It can be accompanied by varying 
degrees of insufficiency or stenosis.
• Cardiovascular—chronic volume overload 
from valvular insufficiency and/or inflow 
obstruction due to valvular stenosis result in 
elevated pulmonary (MVD) or systemic 
(TVD) venous pressures.
• Respiratory—pulmonary edema may 
develop secondary to MVD; pulmonary 
hypertension is a common complication in 
animals with mitral stenosis.
• Neurologic—collapse and/or loss of conscious -
ness, most often with exercise, may occur 
with severe disease due to low cardiac output/hypotension or ventricular arrhythmias in cases 
with severe dynamic outflow obstruction.
GENETICS
TVD appears to be inherited as an autosomal 
recessive trait in dogues de Bordeaux and an 
autosomal dominant with incomplete 
penetrance trait in Labrador retrievers.
These are common congenital cardiac 
anomalies in cats (17% of reported congenital 
cardiac defects in one study). Mitral valve 
malformations often are noted in cats with 
hypertrophic cardiomyopathy. Less frequently 
diagnosed in dogs.
Species
• TVD—increased risk for Labrador retriever, 
German shepherd dog, great Pyrenees, 
possibly Old English sheepdog; also common 
in cats.
• MVD—increased risk in bull terrier, 
Newfoundland, Labrador retriever, Great 
Dane, golden retriever, Dalmatian, and 
Siamese cat.
Variable; signs most often manifest within the 
first few years after birth.
Males are more likely to experience CHF .
SIGNS
• Abdominal distention, weight loss, and 
stunting may be observed with severe TVD.
• Labored respiration common with severe 
MVD.
• Syncope and collapse if critical atrioven-
tricular (AV) valve stenosis, severe outflow 
tract obstruction, associated arrhythmias, or 
CHF .
• A holosystolic murmur is heard over the 
ipsilateral cardiac apex. In severe cases the 
murmur is accompanied by a thrill or gallop 
heart sounds. In animals with valvular stenosis, 
a soft diastolic murmur may be present in the 
same location, but many have no audible 
murmur. A labile systolic ejection murmur may 
be audible in animals with dynamic outflow 
tract obstruction. Silent tricuspid regurgitation 
is well documented in cats with a large regurg -
itant orifice and laminar regurgitant flow.
• Jugular venous distension/pulsation may be 
evident in patients with TVD.
• Evidence of left CHF (tachypnea, dyspnea, 
pulmonary crackles, cyanosis) in animals with 
severe MVD.
• Evidence of right CHF (ascites, peripheral 
edema) with severe TVD.  DIAGNOSIS
• Except for age of onset, congenital AV valve 
insufficiency resembles acquired degenerative 
AV valve insufficiency with regard to history, 
physical examination findings, and clinical 
sequelae.
• The right-sided murmur of tricuspid 
insufficiency may be confused with the 
right-sided murmur of a ventricular septal 
defect.
• Ascites caused by silent tricuspid regurgita-
tion or tricuspid valve stenosis is often 
attributed to pericardial effusion, hepatic 
disease, or caudal vena caval obstruction.
• Dogs and cats with cor triatriatum share 
many of the clinical features of AV valve 
stenosis.
• There is no certain way to distinguish outflow 
tract obstruction due to MVD and obstructive 
hypertrophic cardiomyopathy. If the obstruction 
can be abolished with adrenergic beta blockers 
and LV hypertrophy resolves, it is likely that the 
primary abnormality was MVD.
IMAGING
• Ipsilateral atrial and ventricular enlarge-
ment with valvular insufficiency. Isolated 
atrial enlargement with valvular stenosis. 
Mild left atrial (LA) enlargement with 
dynamic LV outflow obstruction. Cardiac 
silhouette may appear globoid with pro-
nounced enlargement in cases of severe TVD.
• Evidence of left CHF—distended 
pulmonary veins, interstitial or alveolar 
edema in severe MVD.
• Evidence of right CHF—dilated caudal 
vena cava, hepatosplenomegaly, or ascites in 
severe TVD.
• Valvular insufficiency results in ipsilateral 
atrial dilation and eccentric ventricular 
hypertrophy. Doppler echocardiography 
demonstrates a high velocity retrograde 
systolic jet and modestly increased transmitral 
or transtricuspid inflow velocities.
• Valvular stenosis results in ipsilateral atrial 
dilation, while the associated ventricular 
dimensions are normal or small. Valve 
leaflets are often thickened, relatively 
immobile, and fused. Doppler echocardiog -
raphy demonstrates a high-velocity 
transmitral or transtricuspid diastolic jet 
with a reduced EF slope. There may also be 
evidence of concurrent AV valvular 
insufficiency, secondary pulmonary hyper  - 
tension (in cases of mitral stenosis), or 
right-to-left shunting across a patent 
foramen ovale or associated atrial septal 
defect (in cases of tricuspid stenosis).

Canine and Feline, Seventh Edition  155
A
• With MVD, the LV papillary muscles are 
typically flattened and displaced dorsally. 
Chordae tendineae are often short and 
thickened. With TVD, papillary muscles 
and chordae tendineae may be fused, 
creating a curtain-like appearance of the 
tricuspid valve.
• Dynamic LV outflow obstruction in 
patients with MVD is characterized by systolic 
motion of the anterior mitral leaflet toward 
the interventricular septum, increased LV 
outflow tract velocities, eccentric mitral regur -
gitation, and concentric LV hypertrophy.
Cardiac Catheterization
• Indicated only for cases in which diagnosis 
cannot be confirmed by echocardiography or 
if surgical correction anticipated.
• Hemodynamic measurements should 
include ipsilateral atrial and ventricular 
pressures. Additional measurements in 
cases of MVD include pulmonary capillary 
wedge pressure (in lieu of direct LA 
pressure measurement), pulmonary artery 
pressures, and, in cases of dynamic 
obstruction, simultaneous aortic and LV 
pressure recording with medical provo -
cation. Contrast studies are best 
performed with ventricular injection in 
cases of valvular insufficiency, and direct 
atrial injection in cases of valvular stenosis.
ECG
• Findings usually reflect pattern of chamber 
enlargement.
• Severe defects may be accompanied by 
arrhythmias, particularly atrial premature 
beats, supraventricular tachycardia, or atrial 
  TREATMENT
Inpatient treatment required for CHF .
DIET
Sodium restricted if overt or pending CHF .
Owners should be informed of heritability 
and advised against breeding.SURGICAL CONSIDERATIONS
• Valve repair or replacement is available in a 
few centers.
• Balloon valvuloplasty is sometimes effective 
for valvular stenosis.
• For patients with CHF , furosemide 
(1–4 mg/kg q12–24h) and enalapril (0.5 mg/
kg q12h) are used to control congestion, with 
the addition of pimobendan (0.3 mg/kg 
q12h) in cases of valvular insufficiency.
• Supraventricular tachyarrhythmias may be 
managed using digoxin (2–4  μg/kg q12h), a 
calcium channel blocker such as diltiazem 
(1–1.5 mg/kg q8h), or a beta blocker such 
as atenolol (0.5–1.5 mg/kg q12–24h). 
Heart rate should be maintained below 
150 bpm.
• For dynamic outflow tract obstruction, beta 
blockers such as atenolol (0.5–1.5 mg/kg 
q12–24h) may be used to abolish or diminish 
severity of outflow obstruction; however, 
benefit has not been proven.
Standard patient monitoring for cardiac 
medication side effects (e.g., digitalis toxicity, 
azotemia).
  FOLLOW-UP
• Recheck yearly if no signs of CHF .
• Recheck every 3 months if signs of CHF 
(consider thoracic radiographs, ECG, and 
echocardiography).
• CHF—left-sided with MVD; right-sided 
with TVD.
• Collapse or syncope with exercise.
• Paroxysmal supraventricular tachycardia or 
atrial fibrillation with severe disease.
• Depends on severity of underlying defect.
• Guarded to poor with serious defects.  MISCELLANEOUS
• MVD commonly accompanies valvular or 
subvalvular aortic stenosis as well as TVD.
• TVD commonly accompanies pulmonic 
stenosis as well as MVD.
Breeding should be avoided—heritable defect 
and possibility of causing decompensated or 
worsening CHF .
SEE ALSO
• AVVD = atrioventricular valve dysplasia.
• LA = left atrial.
• LV = left ventricular.
• MVD = mitral valve dysplasia.
• RA = right atrial.
• TVD = tricuspid valve dysplasia.
heart disease. In: Fox PR, Sisson D, Moise 
NS. Textbook of Canine and Feline 
Cardiology: Principles and Clinical Practice, 
2nd ed. Philadelphia, PA: Saunders, 1999, 
pp. 520–526.
Oyama MA, Sisson DD, Thomas WP , 
Bonagura JD. Congenital heart disease. 
In: Ettinger SJ, Feldman EC, eds., Textbook 
of Veterinary Internal Medicine, 7th ed. 
St. Louis, MO: Elsevier, 2010, 
pp. 1250–1298.
Strickland KN, Oyama MA. Congenital heart 
disease. In: Tilley LP , Smith FWK, Oyama 
MA, Sleeper MM, eds., Manual of Canine 
and Feline Cardiology, 5th ed. St. Louis, 
MO: Saunders Elsevier, 2016, pp. 218–238.
Author  Michael Aherne
David D. Sisson.
available online(continued)  Atrioventricular Valve Dysplasia

156  Blackwell’s Five-Minute Veterinary Consult  
A
  BASICS
Atrioventricular (AV) valvular stenosis is a 
pathologic narrowing of the mitral or 
tricuspid valve orifice or the presence of an 
obstructive, supravalvular ring.
• AV stenosis increases the resistance to 
ventricular filling.
• Ventricular filling in clinically significant 
disease requires a persistent diastolic pressure 
gradient between atrium and ventricle.
• Concomitant valvular regurgitation is 
common.
• The increased atrial pressure leads to atrial 
dilation, venous congestion, and often to 
congestive heart failure (CHF). Pulmonary 
edema occurs with mitral stenosis (MS); 
whereas ascites, pleural effusion, and chylo  - 
thorax can develop in cases of severe tricuspid 
stenosis (TS).
• The foramen ovale can remain patent 
(PFO) in patients with TS, allowing right- 
to-left shunting with signs of cyanotic heart 
disease.
• Partial AV septal defect (primum atrial 
septal defect [ASD] and abnormal AV valve) 
is observed in some cats with supravalvular 
mitral (ring) stenosis.
• Cardiac output and therefore exercise 
capacity are limited.
• The atrial pressure increases disproportion-
ally with faster heart rates, thereby creating 
the risk for “flash” pulmonary edema in dogs 
or cats with MS.
• Development of atrial tachyarrhythmias, 
especially atrial fibrillation (AF), is associated 
with cardiac decompensation.
• Pulmonary hypertension (PH) can develop 
consequent to MS, leading to exercise 
intolerance and right ventricular hypertrophy. 
This can be severe, especially in cats.
• Respiratory—with MS: bronchial compres-
sion from enlarged left atrium, pulmonary 
edema from left heart failure; potential for 
hemoptysis due to rupture of pulmonary 
venous–bronchial venous connections; pleural 
effusion with atelectasis in TS or in long-
standing MS complicated by PH or AF .
• Hepatobiliary—with TS: hepatic 
congestion, ascites.
GENETICS
• Uncertain in most cases.
• T ricuspid valve dysplasia in Labrador retrievers 
has been localized to a defect in dog chromo -
some 9, inherited as an autosomal dominant 
trait with reduced penetrance. In dogue de 
Bordeaux, tricuspid valve dysplasia has been 
identified as an autosomal recessive trait.INCIDENCE/PREVALENCE
Rare
Worldwide
Species
• MS is overrepresented in bull terriers and 
Newfoundlands, and in Siamese cats.
• TS has been reported most often in Old 
English sheepdogs and Labrador retrievers.
Most patients are presented at a young 
age, although exceptions occur, especially 
in cats.
N/A
SIGNS
• Syncope.
• Exertional dyspnea or tachypnea.
• Cough—MS.
• Abdominal distention—TS.
• Acute posterior paresis—cats with MS and 
arterial thromboembolism.
• Stunted growth.
• Hemoptysis from rupture of intrapulmonary 
vessels—MS.
• Soft diastolic murmur with point of 
maximal intensity over left apex (MS) or right 
hemithorax (TS).
• Holosystolic murmur of mitral or tricuspid 
regurgitation is more often detected.
• Tachypnea, dyspnea from pulmonary 
edema or pleural effusion.
• Crackles from pulmonary edema.
• Jugular distention, jugular pulses, ascites, 
hepatomegaly with TS, or biventricular CHF 
associated with pulmonary hypertension and 
AF in chronic MS.
• Cyanosis from right-to-left shunting with 
TS and PFO or from pulmonary edema 
with MS.
CAUSES
• Usually due to congenital dysplasia of 
mitral or tricuspid valve.
• Supravalvular obstructing rings of tissue 
have been associated with AV stenosis; this is 
especially important in cats.
• Infective endocarditis, intracardiac neoplasia, 
and hypertrophic cardiomyopathy with 
scarring are rare causes of acquired AV valve 
stenosis.
• Acquired TS has been observed due to 
fibrous scarring of the tricuspid valve in dogs 
with transvenous pacing leads.RISK FACTORS
Breed predispositions (see above); see Risk 
Factors for Endocarditis, Infective; permanent 
transvenous pacing.
  DIAGNOSIS
AV valvular stenosis must be differentiated 
from the more common causes of mitral and 
tricuspid regurgitation in the absence of 
stenosis. These include both congenital and 
acquired lesions of the AV valves and support 
apparatus. Cor triatriatum dexter, cor 
triatriatum sinister and double outlet right 
atrium can mimic some of the clinical 
findings of pure tricuspid and mitral valvular 
stenosis, respectively.
May be normal or reflect changes related to 
CHF or drug therapy for CHF .
IMAGING
• Atrial enlargement is the most common 
and outstanding feature; may see generalized 
cardiomegaly, especially with AV valve 
regurgitation.
• MS—may see pulmonary venous conges-
tion and pulmonary edema; intrapulmonary 
hemorrhage can be misinterpreted as 
pneumonia or another parenchymal disease.
• TS—may see hepatomegaly; increased 
diameter of caudal vena cava.
• Diagnostic test of choice.
• T wo-dimensional echocardiography reveals a 
markedly dilated atrium and attenuated valve 
excursion during diastole, often with thickened, 
irregular AV valve leaflets; valve leaflets may 
appear to “dome” during diastole (see Web Video 
1). A supravalvular obstructing ring also may be 
evident, as well as other lesions (see Causes).
• Color-flow imaging reveals a turbulent 
diastolic jet that originates proximal to the 
stenotic valve and projects toward the apex of 
the ventricle (see Web Video 2); AV valve 
regurgitation is often present (see Web Videos 
3 and 4). Concurrent defects may also be 
noted, such as PFO, ASD, or bridging septal 
leaflet (see Web Video 5).
• M-mode studies show an enlarged atrium 
and concordant motion of the AV valve 
leaflets, indicating commissural fusion (see 
Web Figure 1); the E-to-F slope is decreased.Atrioventricular Valvular Stenosis
• Spectral Doppler studies show increased 
diastolic transvalvular flow velocities; 
prolonged calculated pressure half-time is a 
hallmark feature; E-wave/A-wave amplitude 
reversal is often evident in cases still in 
normal sinus rhythm (see Web 
Figures 2, 3, 4).

Canine and Feline, Seventh Edition  157
A
• Right-sided chamber enlargement in MS 
with pulmonary hypertension or with chronic 
AF (see Web Figure 4).
• Right atrium—injection demonstrates 
markedly dilated atrium in TS; with 
concurrent PFO or ASD, opacification of the 
left atrium is also observed following right 
atrial injection.
• Might visualize thickened, irregular valve 
leaflets or a stenotic valve funnel.
• Ventricular injection often reveals valvular 
• There can be delayed opacification of the 
ventricles and great vessels.
• A diastolic pressure gradient is identified 
between atrium and ventricle. A large “A” 
wave is common if atrial function is 
preserved.
• High left atrial, pulmonary capillary 
wedge, and pulmonary artery pressures 
occur in MS.
• High right atrial and central venous 
pressures are present in TS.
• Ventricular pressure may be normal in the 
absence of concurrent defects.
ECG
• Variable enlargement and ventricular 
conduction patterns are observed. Widened 
or tall P-waves are commonly observed.
• Splintered R-waves are present in some 
dogs with tricuspid dysplasia.
• Axis deviation due to hypertrophy or 
ventricular conduction disturbances is 
relatively common in cats with mitral valve 
• Ectopic rhythms, especially of atrial origin, 
are often observed. AF is the most important 
rhythm disturbance as atrial contribution to 
filling is lost and the R-to-R intervals vary 
with short cycles, increasing the mean 
diastolic gradient.
• The AV valve is abnormal, with thickened 
leaflets and fused commissures. Other lesions 
may be identified such as a supramitral ring 
(see Causes).
• Many cases also have abnormal chordae 
tendineae and papillary muscles.
• Atrial dilation and hypertrophy are common.
• PFO with TS or partial AV septal defect 
(primum ASD and bridging septal leaflet) 
with supravalvular mitral (ring) stenosis.
  TREATMENT
• Patients in overt CHF should be treated 
with inpatient medical management.• Surgical or catheter-based interventions can 
be considered once heart failure has been 
stabilized.
• Control of heart rhythm disturbances, 
especially AF , is also important.
• These patients are typically complicated 
and consultation with a cardiologist is highly 
• Electrocardioversion of AF should be 
considered, but advanced atrial disease can 
render the procedure less effective or limit the 
duration of sinus rhythm.
• Sedation with butorphanol is appropriate 
for dyspneic patients.
• Oxygen therapy should be administered to 
patients with dyspnea or hypoxemia from 
left-sided CHF .
• Fluid therapy is typically contraindicated in 
patients with overt CHF , except in cases of 
moderate to severe azotemia, renal 
compromise, or severe dehydration. Therapeutic 
paracentesis may be considered in patients 
with pleural effusion or tympanic ascites.
ACTIVITY
Exercise restriction is important to 
recommend for any animal with this 
condition, because tachycardia increases the 
mean gradient across the stenotic valve, 
predisposing to pulmonary edema or venous 
congestion (see Web Figures 3 and 4). Cage 
rest is ideal for patients with CHF .
DIET
Feed a sodium-restricted diet to patients in 
CHF .
Clients must be advised of symptoms 
associated with CHF and the urgency of 
treatment, particularly with left-sided CHF . 
Likelihood of recurrent bouts of CHF should 
also be discussed.
• Surgical valve replacement or repair 
requires cardiopulmonary bypass or 
hypothermia; cost, availability, and high 
complication and mortality rates are greatly 
limiting factors.
• Balloon valvuloplasty is an alternative referral 
treatment and has been used successfully for 
managing some cases of AV stenosis.
CHF
• Diuretic—Furosemide: dogs, 2–4 mg/kg 
IV/IM/SC/PO q8–24h; cats, 1–4 mg/kg IV/
IM/SC/PO q8–24h. Torsemide: dogs, 
0.2–0.5 mg/kg PO q12–24h; cats, 1.25 mg 
PO q12–48h.• Angiotensin-converting enzyme (ACE) 
inhibitor—enalapril or benazepril: dogs, 
0.25–0.5 mg/kg PO q12h; cats, 0.25–
0.5 mg/kg PO q12–24h; see Follow-Up for 
patient monitoring.
• Nitroglycerin paste (1/4 to 1 inch topically 
q12h) to reduce pulmonary venous pressures, 
but this has not been evaluated critically.
Atrial Tachyarrhythmias
• Digoxin—dogs, 3–5  μg/kg PO q12h; cats, 
one-fourth of a 0.125 mg tablet PO 
q24–48h; adjust dosage based on serum 
• Beta blockers such as atenolol or the 
calcium channel blocker diltiazem for 
suppression of frequent atrial premature 
complexes and for heart rate control in atrial 
tachyarrhythmias such as atrial tachycardia/
flutter/fibrillation. Beware when using these 
drugs in uncontrolled CHF .
• Typical atenolol dosages—dogs, 0.25–
1.0 mg/kg q12h; cats, 6.25–12.5 mg/cat 
q12–24h; start low and titrate to effect.
• Diltiazem dosages—dogs, 2–6 mg/kg daily 
in two (long-acting diltiazem) or three 
divided dosages; start low and titrate to effect; 
cats, 7.5 mg diltiazem HCl PO q8h. Higher 
dosages are sometimes needed.
• Sotalol for intractable/recurrent arrhythmias—  
dogs, 1–2.5 mg/kg PO q12h; cats, 
10–20 mg/cat q12h.
• Dogs can be referred for electrocardiover-
sion to convert AF to sinus rhythm (with 
follow-up therapy with sotalol or amiodar-
one); however, reversion to AF is common 
owing to marked atrial dilatation.
Pulmonary Hypertension
• Sildenafil—dogs, 0.5–3 mg/kg PO q8–12 
hours.
Primary afterload reducers such as hydralazine 
or amlodipine should be avoided in treatment 
of heart failure from pure MS due to risk of 
• As a general rule, pimobendan is 
relatively contraindicated in pure valvular 
stenosis; however, many dogs and cats with 
advanced CHF have been treated with this 
drug with apparent success, especially when 
there is combined stenosis/regurgitation of 
the valve.
• Use ACE inhibitors or other vasodilators 
judiciously in patients with CHF; cardiac 
output is limited and vasodilation may induce 
hypotension. Monitor arterial blood pressure 
and renal function.
• Furosemide and ACE inhibitors can affect 
kidney function, alter blood electrolytes, and 
reduce blood pressure; these parameters 
should be monitored.(continued)  Atrioventricular Valvular Stenosis

158  Blackwell’s Five-Minute Veterinary Consult  
A
• Sildenafil can also reduce systemic blood 
pressure and should not be used with nitro  - 
glycerin paste or other nitrates.
Spironolactone (2 mg/kg PO q12–24h) 
should be considered as an ancillary diuretic 
and for its antifibrotic benefit (as an 
aldosterone antagonist).
  FOLLOW-UP
• Thoracic radiographs for pulmonary edema 
or pleural effusion.
• Echocardiography with Doppler studies—
to estimate pulmonary pressures and 
subjectively assess right heart function if on 
sildenafil.
• Digoxin level—check 7–10 days following 
institution of therapy; 8- to 12-hour trough 
should be 0.8–1.5 ng/mL.
• Renal function, electrolyte status, and 
arterial blood pressure when on diuretic and/
or ACE inhibitor.
• Standard rhythm ECG or Holter (ambula-
tory ECG) if arrhythmias are present.
• CHF .
• Atrial fibrillation.
• Syncope.
• Arterial thromboembolism—cats with MS.
• Pulmonary hemorrhage with MS.EXPECTED COURSE AND 
PROGNOSIS
• Morbidity is high; except for mild cases, 
prognosis is generally poor once an animal 
becomes symptomatic. However, some 
animals will live for many years even with 
relatively severe stenosis of the mitral or 
• Surgical intervention or balloon valvulo-
plasty might alter course of disease, but data 
are limited.
Concurrent congenital defects are common, 
e.g., subaortic stenosis in MS, PFO in TS, 
primum ASD in cats with supravalvular 
The possibility that this may be a heritable 
defect must be considered in assessing 
suitability of the animal for breeding, 
particularly in breeds with a predilection for 
this defect. The additional hemodynamic 
burden of gestation may be poorly tolerated 
by an already compromised heart. In general, 
breeding is strongly discouraged.
SYNONYMS
• AV dysplasia with stenosis.
• Supravalvular mitral ring.SEE ALSO
• Atrioventricular Valve Dysplasia.
• AF = atrial fibrillation.
• ASD = atrial septal defect.
• MS = mitral stenosis.
• PFO = patent foramen ovale.
• PH = pulmonary hypertension.
• TS = tricuspid stenosis.
Arndt JW, Oyama MA. Balloon valvuloplasty 
of congenital mitral stenosis. J Vet Cardiol 
2013, 15:147–151.
Brown WA, Thomas WP . Balloon valvulo -
plasty of tricuspid stenosis in a Labrador 
retriever. J Vet Intern Med 1995, 
9:419–424.
Campbell FE, Thomas WP . Congenital 
supravalvular mitral stenosis in 14 cats. J 
Vet Cardiol 2012, 14:281–292.
Lehmkuhl LB, Ware WA, Bonagura JD. 
Mitral stenosis in 15 dogs. J Vet Intern Med 
1994, 8:2–17.
Stamoulis ME, Fox PR. Mitral valve stenosis 
in three cats. J Small Anim Pract 1993, 
34:452–456.
Authors  Lora S. Hitchcock and John D. 
Bonagura
Consulting Editor  Michael AherneAtrioventricular Valvular Stenosis  (continued)

Canine and Feline, Seventh Edition  159
A Azotemia and Uremia
  BASICS
• Azotemia is an excess of urea, creatinine, or 
other nonprotein nitrogenous substances in 
blood, plasma, or serum.
• Uremia is the polysystemic toxic syndrome 
resulting from marked loss in kidney functions. 
Uremia occurs simultaneously in animals 
with increased quantities of urine constituents 
in blood (azotemia), but azotemia may occur 
in the absence of uremia.
• Azotemia can be caused by (1) increased 
production of nonprotein nitrogenous 
substances, (2) decreased glomerular filtration 
rate (GFR), or (3) reabsorption of urine that 
has escaped from the urinary tract into the 
bloodstream. High production of nonprotein 
nitrogenous waste substances may result from 
high intake of protein (diet or gastrointestinal 
bleeding) or accelerated catabolism of endo  - 
genous proteins. GFR may decline because of 
reduced renal perfusion (prerenal azotemia), 
acute or chronic kidney disease (renal 
azotemia), or urinary obstruction (postrenal 
azotemia). Reabsorption of urine into the 
systemic circulation may also result from 
leakage of urine from the excretory pathways 
(also a form of postrenal azotemia).
• Pathophysiology of uremia—incompletely 
understood; may be related to (1) metabolic 
and toxic systemic effects of waste products 
retained because of renal excretory failure, (2) 
deranged renal regulation of fluid, electrolytes, 
and acid-base balance, and (3) impaired renal 
production and degradation of hormones and 
other substances (e.g., erythropoietin and 
1,25-dihydroxycholecalciferol).
• Uremia affects all body systems.
• Cardiovascular—arterial hypertension, left 
ventricular hypertrophy, heart murmur, 
cardiomegaly, cardiac rhythm disturbances.
• Endocrine/metabolic—renal secondary 
hyperparathyroidism, inadequate production 
of calcitriol and erythropoietin, hypergas-
trinemia, weight loss.
• Gastrointestinal—anorexia, nausea, 
vomiting, diarrhea, uremic stomatitis, 
xerostomia, uremic breath, constipation.
• Hemic/lymph/immune—anemia and 
immunodeficiency.
• Neuromuscular—dullness, lethargy, fatigue, 
irritability, tremors, gait imbalance, flaccid 
muscle weakness, myoclonus, behavioral 
changes, dementia, isolated cranial nerve 
deficits, seizures, stupor, coma, impaired 
thermoregulation (hypothermia).
• Ophthalmic—scleral and conjunctival 
injection, retinopathy, acute-onset blindness.
• Respiratory—dyspnea.
• Skin/exocrine—pallor, bruising, increased 
shedding, unkempt appearance, loss of 
normal sheen to coat.SIGNALMENT
SIGNS
Azotemia may not be associated with 
historical or physical abnormalities. Unless 
patient has uremia, clinical findings are 
limited to disease responsible for azotemia.
• Declining appetite or anorexia.
• Fatigue.
• Weakness.
• Polyuria.
• Changes in urine volume.
• Poor haircoat or unkempt appearance.
• Muscle wasting/sarcopenia/cachexia.
• Mental depression.
• Pallor.
• Petechiae and ecchymoses.
• Dull and unkempt haircoat.
• Uremic breath.
• Uremic stomatitis (including oral ulcers, 
infarctions of the tongue).
• Scleral and conjunctival injection.
• Relative hypothermia.
CAUSES
Prerenal Azotemia
• Reduced renal perfusion due to low blood 
volume or low blood pressure.
• Accelerated production of nitrogenous waste 
products because of enhanced catabolism of 
tissues in association with infection, fever, 
trauma, corticosteroid excess, or burns.
• Increased gastrointestinal digestion and 
absorption of protein sources (diet or gastro  - 
intestinal hemorrhage).
Renal Azotemia
Acute or chronic kidney diseases (primary 
kidney disease affecting glomeruli, renal 
tubules, renal interstitium, and/or renal 
vasculature) that impair at least 75% of 
kidney function (GFR).
Postrenal Azotemia
Urinary obstruction; rupture of excretory 
pathway.
• Medical conditions—kidney disease, 
hypoadrenocorticism, low cardiac output, 
hypotension, fever, sepsis, liver disease, pyometra, 
hypoalbuminemia, dehydration, acidosis, 
exposure to nephrotoxic chemicals, gastrointesti -
nal hemorrhage, urolithiasis, urethral plugs in 
cats, urethral trauma, and neoplasia.
• Advanced age may be a risk factor.
• Drugs—potentially nephrotoxic drugs, nonsteroidal anti-inflammatory drugs, 
diuretics, antihypertensive medications; 
failure to adjust dosage of drugs primarily 
eliminated by the kidneys to correspond with 
decline in renal function.
• Toxins—ethylene glycol, grapes (dogs), 
lilies (cats).
  DIAGNOSIS
• Dehydration, poor peripheral perfusion, low 
cardiac output, history of recent fluid loss, 
high-protein diet—rule out prerenal azotemia.
• Recent onset of altered urine output (high 
or low), clinical signs consistent with uremia, 
exposure to possible nephrotoxicants or 
ischemic renal injury, or kidney size normal or 
enlarged—rule out acute kidney injury (AKI).
• Progressive weight loss, polyuria, polydipsia, 
small kidneys, disparate kidney size (cats— 
big kidney and little kidney), pallor, and signs 
of uremia that have developed over several 
weeks to months—rule out chronic kidney 
disease (CKD).
• Abrupt decline in urine output and onset of 
signs of uremia; disparate kidney size, dysuria, 
stranguria, and hematuria; large urinary 
bladder or fluid-filled abdomen—rule out 
postrenal azotemia.
CBC
• Nonregenerative anemia (normocytic, 
normochromic)—often present with CKD.
• Hemoconcentration—often present with 
prerenal azotemia; can also be seen with AKI 
Biochemistry
• Serial determinations of serum urea 
nitrogen and creatinine concentrations 
may help differentiate the cause of azotemia. 
Appropriate therapy to restore renal perfusion 
typically yields a dramatic reduction in 
azotemia in patients with prerenal azotemia 
(typically within 24–48 hours). Correcting 
obstruction to urine flow or a rent in the 
excretory pathway typically is followed by a 
rapid reduction in the magnitude of azotemia.
• Hyperkalemia may be consistent with 
postrenal azotemia, primary renal azotemia 
due to oliguric renal failure, or prerenal 
azotemia associated with hypoadrenocorticism.
• Increased serum albumin and globulin 
concentration suggest prerenal component.
Urinalysis
• Urine specific gravity (USG) ≥1.030 (dog) 
and ≥1.035 (cat) supports a diagnosis of 
prerenal azotemia. Administration of fluid 
therapy before urine collection may interfere 
with interpretation of USG.
• Azotemic patients that have not been treated 
with fluids and have USG <1.030 (dog) and 
<1.035 (cat) typically have primary renal 
azotemia. A notable exception is glomerular

160  Blackwell’s Five-Minute Veterinary Consult  
A
disease, which is sometimes characterized by 
glomerulotubular imbalance, where adequate 
urine-concentrating ability may persist despite 
sufficient renal glomerular damage to cause 
primary renal azotemia; these patients are 
recognized by moderate to marked proteinuria 
in the absence of hematuria and pyuria.
• USG is not useful in identifying postrenal 
azotemia.
Endogenous or exogenous creatinine, iohexol, 
or inulin clearance tests or other specific tests 
of GFR may be used to confirm that azotemia 
is caused by reduced GFR.
IMAGING
• Abdominal radiographs—used to deter-
mine kidney size (small kidneys consistent 
with CKD; mild-to-moderate enlargement of 
kidneys may be consistent with AKI or 
urinary obstruction) and to rule out urinary 
obstruction (marked dilation of urinary 
bladder or mineral densities within excretory 
pathway).
• Ultrasonography—may detect changes in 
echogenicity of renal parenchyma and size 
and shape of kidneys; useful to rule out 
postrenal azotemia characterized by 
distension of excretory pathway and uroliths 
or masses within or impinging on excretory 
pathway and intra-abdominal fluid accumu -
lation (with rupture of excretory pathway).
• Excretory urography, pyelography, or 
cystourethrography—may help establish 
diagnosis of postrenal azotemia due to urinary 
obstruction or rupture of excretory pathway.
Renal biopsy can confirm the diagnosis of 
primary kidney disease, to differentiate acute 
from chronic kidney disease, and to attempt 
to establish the underlying disease process 
responsible for kidney disease.
  TREATMENT
• Prerenal azotemia caused by impaired renal 
perfusion—correct the underlying cause of 
renal hypoperfusion; aggressiveness of 
treatment depends on severity of underlying 
• Primary renal azotemia and associated 
uremia—(1) specific therapy directed at 
halting or reversing primary disease process 
affecting the kidneys, and (2) symptomatic, 
supportive, and palliative therapies that 
ameliorate clinical signs of uremia; minimize 
clinical impact of deficits and excesses in 
fluid, electrolyte, acid-base balances; 
minimize effects of inadequate renal 
biosynthesis of hormones and other 
substances; and maintain adequate 
nutrition.
• Postrenal azotemia—eliminate urinary 
obstruction or repair rents in excretory 
pathway; supplemental fluid administra -
tion often required to prevent dehydration that may develop during solute diuresis 
that follows correction of postrenal 
azotemia.
• Fluid therapy—indicated for most 
azotemic patients; isotonic balanced 
crystalloid is preferred replacement fluid, 
followed by hypotonic maintenance fluid 
administration. Determine fluid volume to 
administer on basis of severity of dehydra -
tion or volume depletion. If no clinical 
dehydration is evident, cautiously assume 
that patient is <5% dehydrated and 
administer corresponding volume of fluid. 
Provide 25% of calculated fluid deficit in 
first hour. Thereafter, serially monitor 
perfusion (capillary refill time, pulse 
pressure, heart rate, and temperature of 
feet), blood pressure, and urine output to 
assess adequacy of fluid therapy. If perfusion 
has not improved, additional fluid should 
be administered. Provide the remaining 
fluid deficit over the next 12–24 hours. 
Fluid therapy should be cautiously 
administered to patients with overt or 
suspected cardiac failure and patients that 
are oliguric or anuric.
• Consider feeding diets formulated for 
kidney disease to reduce magnitude of 
azotemia, hyperphosphatemia, and acidosis.
• Symptomatic therapy for myriad manifesta-
tions of uremia.
• Omeprazole (1 mg/kg q12h) may be used 
to reduce gastric hyperacidity.
• Antiemetics such as maropitant (1 mg/kg 
q24h) are indicated for vomiting.
Administration of nephrotoxic drugs.
• Use caution when administering drugs 
requiring renal excretion. Consult approp -
riate references concerning dose-reduction 
schedules or adjustments of maintenance 
intervals.
• Cautiously administer fluids to oligoanu -
ric patients. Monitor urine production 
rates and body weight during fluid therapy 
to minimize likelihood of inducing over  - 
hydration.
• Stop fluid therapy in overhydrated oliguric/
anuric patients. Use caution in administering 
drugs that may promote hypovolemia or 
hypotension (e.g., diuretics); carefully 
monitor response to such drugs by assessing 
hydration status, peripheral perfusion, and 
blood pressure, with serial evaluation of renal 
function tests.
• Corticosteroids may worsen azotemia by 
increasing catabolism of endogenous proteins.
Serum urea nitrogen and creatinine concen  - 
trations 24 hours after initiating fluid 
administration; also urine production, blood 
pressure, body weight, and hydration status.
• Failure to correct prerenal azotemia caused 
by renal hypoperfusion rapidly could result in 
ischemic primary kidney disease.
• Primary renal azotemia can progress to uremia.
• Failure to restore normal urine flow in 
patients with postrenal azotemia can result in 
progressive renal damage or death due to 
hyperkalemia and uremia.
An association may exist between hypoka-
lemia and azotemia in cats.
Primary renal failure may occur in animals of 
any age, but geriatric dogs and cats appear to 
be at substantially higher risk for both acute 
and chronic kidney disease; these patients are 
also at higher risk for prerenal and postrenal 
causes of azotemia.
• Data on azotemia and pregnancy are very 
limited.
• Pregnant azotemic animals—pharmacologic 
agents excreted by nonrenal pathways are 
SEE ALSO
• Acute Kidney Injury.
International Renal Interest Society (IRIS): 
www.iris-kidney.com.
Polzin D. Chronic kidney disease. In: Ettinger 
SJ, Feldman EC, eds., Textbook of Veterinary 
Internal Medicine, 7th ed. Philadelphia, PA: 
Saunders, 2010, pp. 2036–2067.
Ross L. Acute renal failure. In: Bonagura JD, 
T wedt DC, eds. Kirk’s Veterinary Therapy 
XIV. Philadelphia, PA: Saunders, 2009, 
pp. 879–882.
Author  David J. Polzin
Consulting Editor  J.D. FosterAzotemia and Uremia  (continued)

Canine and Feline, Seventh Edition  161
B
  BASICS
OVERVIEW
• Caused by protozoal parasites of the genus 
Babesia. Babesia  spp. infect mammalian red 
blood cells (RBCs). • Large Babesia  spp. that 
infect dogs: ◦ Babesia vogeli  is transmitted by 
Rhipicephalus sanguineus  and has a worldwide 
distribution. ◦ Babesia canis  is transmitted by 
Dermacentor reticulatus  and is primarily found 
in Europe. ◦ Babesia rossi  is transmitted by 
Haemaphysalis leachi  and is primarily found 
in Africa. ◦ Babesia  sp. (Coco)—tick vector is 
unknown; identified primarily in splenec­
tomized and immune ­suppressed dogs in the 
United States. • Small Babesia  spp. (2–5  μm) 
that infect dogs: ◦ B. gibsoni —worldwide 
distribution; most common Babesia  sp. 
disease in the United States.  
◦ B. conradae  (also B. gibsoni  [United States/
California])— only reported in California. 
◦ Babesia vulpes  (also Theileria Vulpes , 
Spanish dog piroplasm, and B. microti ­like 
parasite)—reported in Europe and the United 
States. • Several case reports of novel Babesia  
sp. and other piroplasms (i.e., T. equi)  
infecting dogs. • Small piroplasms (2–5  μm) 
that infect cats: ◦ B. felis —reported in 
Africa. ◦ Cytauxzoon felis —reported in the 
United States. • Infection may occur either 
by tick transmission, direct transmission via 
blood transfer during dog bites, blood 
transfusions, or transplacentally. 
• Incubation period averages approximately 
2 weeks, but some cases are not clinically 
diagnosed for months to years. • Piroplasms 
infect and replicate in red blood cells (RBCs), 
resulting in both direct and immune ­
mediated hemolytic anemia. • Immune ­
mediated hemolytic anemia is more clinically 
important than parasite ­induced RBC 
destruction, since severity of signs does not 
depend on degree of parasitemia.
Systems Affected
• Hemic/lymphatic/immune—anemia, 
thrombocytopenia (bleeding tendencies rare), 
fever, splenomegaly, lymphadenomegaly, 
vasculitis.  • Hepatobiliary—mild to 
moderate increase in liver enzyme activities.  
• Nervous—cerebral babesiosis, weakness, 
disorientation, collapse (most common with 
B. canis rossi ).  • Renal/urologic—renal failure 
(B. rossi  and B. vulpes ).
• Any age or breed of dog can be infected. 
• B. vogeli  infections are more prevalent in 
greyhounds. • B. gibsoni  infections are more 
prevalent in American pit bull terriers.  • Any 
age or breed of cat can be infected, but to 
date, only C. felis  has been reported in the 
United States.SIGNS
• Similar in dogs and cats.  • Peracute, acute, 
or chronic. • Some carrier animals have no 
detectable clinical signs. • Dogs—lethargy, 
anorexia, pale mucous membranes, fever, 
splenomegaly, lymphadenomegaly, pigmenturia, 
icterus, weight loss, discolored stool. 
• Cats—lethargy, anorexia, pale mucous 
membranes, icterus.
• History of tick attachment. • Splenectomized 
animals develop more severe clinical disease. 
• History of splenectomy or chemotherapy 
is risk factor for Babesia  sp. (Coco) 
infection. • Immune suppression may cause 
clinical signs and increased parasitemia in 
chronically infected dogs. • History of recent 
dog­bite wound is risk for B. gibsoni  (Asia) 
infection. • Recent blood transfusion from 
subclinically infected donor.
  DIAGNOSIS
• Any cause of immune ­mediated 
hemolytic anemia or thrombocytopenia, 
including idiopathic immune ­mediated 
ehrlichiosis, Rocky Mountain spotted 
fever, systemic lupus erythematosus, 
neoplasia, endocarditis, hemotropic 
mycoplasmosis (haemobartonellosis), and 
cytauxzoonosis. • A positive Coombs’ test 
does not rule out babesiosis, since many 
animals with babesiosis are also Coombs’ 
positive. • Non­immune ­mediated 
hemolytic anemia, including microangio­
pathic anemia, caval syndrome, splenic 
torsion, disseminated intravascular 
coagulation (DIC), Heinz body anemia, 
pyruvate kinase deficiency, phosphofructo­
kinase deficiency. • Hepatic and posthepatic 
jaundice.
• Anemia—absent to severe; usually 
regenerative (reticulocytosis) unless signs are 
very acute; in severe cases, packed cell volume 
(PCV) <10%. • Thrombocytopenia—usually 
moderate to severe; some animals have thrombo ­ 
cytopenia without anemia; most common 
hematologic abnormality.  • Both leukocytosis 
and leukopenia reported. • Hyperbilirubinemia, 
depending on rate of hemolysis. 
• Hyperglobulinemia is common in chronic 
infections and may be the only biochemical 
abnormality in some animals. • Mildly 
elevated liver enzyme activities from anemia/
hypoxia.  • Proteinuria and hypoalbuminemia 
(protein ­losing nephropathy) may occur. 
• Azotemia and metabolic acidosis secondary 
to renal failure have been reported with B. canis rossi , B. gibsoni , and B. vulpes . 
• Bilirubinuria is common. 
• Hemoglobinuria is detected less commonly 
in United States than in Africa.
• Microscopic examination of stained thin or 
thick blood smears—can provide definitive 
diagnosis (not to species level); sensitivity 
depends on microscopist experience and 
staining technique; most success using a quick 
modified Wright stain; capillary blood may 
enhance sensitivity.  • Indirect fluorescent 
antibody (IFA)—serum antibody test; cross ­ 
reactive antibodies can prevent differentiation 
of species and subspecies; some infected 
animals, particularly young dogs, may have no 
detectable antibodies.  • PCR—identifies 
presence of Babesia  DNA in a biologic sample 
(usually ethylenediaminetetra ­acetic acid 
[EDTA] anticoagulated whole blood); can 
differentiate subspecies and species.
  TREATMENT
• Inpatient or outpatient care depending on 
severity of disease.  • Hypovolemic animals 
should receive aggressive fluid therapy.  
• Severely anemic animals require blood 
transfusion.
• Combination therapy of azithromycin 
(10 mg/kg PO q24h for 10 days) and 
atovaquone (13.5 mg/kg PO q8h for 10 days) 
is the treatment of choice and the only 
treatment that can potentially clear B. gibsoni  
(Asia) infections in dogs; in a controlled study, 
85% of dogs cleared the infection after 
treatment.  • Imidocarb dipropionate (FDA 
approved; 6.6 mg/kg SC/IM every 1–2 
weeks) and diminazine aceturate (not FDA 
approved; 3.5–7 mg/kg SC/IM every 1–2 
weeks) decrease morbidity and mortality in 
affected animals; they may completely clear 
B. canis and B. vogeli  infections, but not B. 
gibsoni . • A combination of clindamycin 
(25 mg/kg PO q12h), metronidazole (15 mg/
kg PO q12h), and doxycycline (5 mg/kg PO 
q12h) had been associated with elimination 
or reduction of parasite below the limit of 
detection of PCR testing in dogs; 
unfortunately, a well ­defined treatment 
course has not been established, with 
treatment times ranging from 24 to 92 days; 
minimum duration of therapy of 90 days 
recommended.  • Combination of 
doxycycline (7–10 mg/kg PO q24h), 
enrofloxacin (2–2.5 mg/kg PO q12h), and Babesiosis

162  Blackwell’s Five-Minute Veterinary Consult  
B
metronidazole (5–15 mg/kg PO q12h) for 
6 weeks was associated with clinical 
remission in 85% of dogs, but PCR was not 
performed to assess effect on parasitemia.  
• Metronidazole (25–50 mg/kg PO q24h for 
7 days), clindamycin (12.5–25 mg/kg PO 
q12h for 7–10 days), or doxycycline (10 mg/kg 
PO q12h for 7–10 days) as single ­agent 
treatments may decrease clinical signs but 
not clear infections. • Primaquine phosphate 
(1 mg/kg IM single injection) is the 
treatment of choice for B. felis . • Since the 
anemia and thrombocytopenia are often 
immune mediated, immunosuppressive 
agents, such as prednisone (2.2 mg/kg/day 
PO), may be indicated in some cases that 
are not responding to antiprotozoal 
treatments alone; prolonged immune 
suppressive therapy before  specific 
antiprotozoal therapy is contraindicated.  
• Antibabesial drugs (imidocarb and 
diminazene) can cause cholinergic signs that 
can be minimized by administering atropine 
(0.02 mg/kg SC 30 min prior to administration).
High doses of antibabesial drugs (imidocarb 
and diminazene) have resulted in liver and 
kidney failure.  FOLLOW-UP
• Recheck CBC and biochemistry as needed to 
monitor resolution of anemia, thrombocyto­
penia, icterus, etc. • Most patients have clinical 
response within 1–2 weeks of treatment.  • 2–3 
consecutive negative PCR tests beginning 2 
months post treatment should be performed to 
rule out treatment failure and persistent 
parasitemia; IFA titers are not recommended 
for follow ­up because titers may persist for 
years.  • Long ­term follow ­up of B. conradae , 
B. vulpes , or B. felis  after treatment has not been 
reported. • When a dog housed in a multidog 
kennel is diagnosed with babesiosis, all dogs in 
that kennel should be screened, since there is a 
high percentage of carrier animals in kennel 
situations.  • Coinfection with other vector ­
transmitted pathogens (e.g., Ehrlichia , 
hemotropic Mycoplasma , Leishmania ) should be 
considered, especially in animals that fail to 
respond to treatment.
Recent studies suggest that using acaracides 
can reduce transmission with Babesia  spp. All 
attached ticks should be removed as soon as 
possible. Vaccines for B. canis  and B. rossi  are 
available in Europe, but may not confer 
protection against other Babesia  spp. Tick 
control is important for disease prevention.  MISCELLANEOUS
All potential blood donors should test 
negative for Babesia  spp.
N/A
T ransplacental transmission.
• EDTA = ethylenediaminetetra ­acetic acid.
Birkenheuer AJ, Correa MT, Levy MG, 
Breitschwerdt EB. Geographic distribution 
of babesiosis among dogs in the United 
States and association with dog bites: 150 
cases (2000–2003). J Am Vet Med Assoc 
2005, 227(6):942–947.
Solano ­Gallego L, Baneth G. Babesiosis in 
dogs and cats—expanding parasitological 
and clinical spectra. Vet Parasitol 2011, 
181(1):48–60.
Author  Adam J. Birkenheuer
Consulting Editor  Amie KoenigBabesiosis  (continued)

Canine and Feline, Seventh Edition  163
B
  BASICS
OVERVIEW
• Baclofen is centrally acting skeletal muscle 
relaxant used to prevent spasticity in people 
with multiple sclerosis, cerebral palsy, and spinal 
disorders. • Binds to gamma-aminobutyric acid 
(GABAB) receptors and prevents release of 
inhibitory neurotransmitters and substances. 
• Has been used extra-label in dogs to reduce 
urethral resistance (1–2 mg/kg PO q8h), but is 
rarely recommended due to narrow margin of 
safety; use in cats not recommended. • Oral 
doses as low as 0.7 mg/kg in dogs have caused 
depression, dyspnea, and hypothermia. • Death 
has been documented in dogs at 2.3 mg/kg, but 
more likely at 8–16 mg/kg. • These organ 
systems are predominantly affected:
◦ Cardiovascular. ◦ Gastrointestinal. 
◦ Musculoskeletal. ◦ Nervous. ◦ Respiratory.
• Accidental exposure in dogs is more 
frequently reported than in cats, but any 
animal may be at risk for poisoning. 
• Cats are extremely sensitive to baclofen.
SIGNS
• Signs begin within 15–90 minutes of 
ingestion but, rarely, may be delayed several 
hours. • Common signs—vocalization, 
vomiting, ataxia, disorientation, hypersalivation, 
depression, weakness, coma, flaccid paralysis, 
recumbency, seizures, and hypothermia. 
• Life-threatening signs—dyspnea, respiratory 
depression, and arrest secondary to 
diaphragmatic/intercostal muscle paralysis.
Pet owners with medical conditions such as 
multiple sclerosis, cerebral palsy, and spinal 
disorders are more likely to have baclofen in 
the home.
  DIAGNOSIS
• Toxic—barbiturates, benzodiazepines, 
depressants, ethanol, ethylene glycol, cannabis/
marijuana, illicit drugs (LSD, phencyclidine 
[PCP], hallucinogenic mushrooms), methanol, 
opioids, propylene glycol, tranquilizers, xylitol. 
• Lower motor neuron disease (e.g., botulism, 
Neospora , tick paralysis, Toxoplasma ). • Metabolic 
(e.g., hepatic encephalopathy, hypoglycemia, etc.).
No specific abnormalities expected, but 
should be used to rule out other causes.
• Arterial blood gas analysis (hypoxemia, 
oxygenation, and ventilation). • Pulse oximetry (hypoxemia). • End tidal 
CO2 (hypercapnia or hypoventilation). 
• Baclofen serum or urine concentrations to 
confirm exposure; not helpful for case 
management.
IMAGING
Thoracic radiographs (aspiration pneumonia 
secondary to severe sedation).
  TREATMENT
• Many cases quickly become serious and 
referral to a 24-hour critical care center 
should be considered. • T reatment focused 
on decontamination and supportive care. 
• Induce emesis following recent ( <1 hour) 
ingestion in asymptomatic patients only if 
have not already vomited; consider gastric 
lavage for very large ingestions. • One dose of 
activated charcoal with sorbitol. • IV fluid 
crystalloids at 1.5–2.5 × maintenance to support 
organ perfusion and enhance elimination. 
• Monitor for cardiac arrhythmias, hypo -
ventilation, and aspiration pneumonia. 
• Oxygen if respiratory depression; ventilator 
support if severe respiratory depression/failure. 
• Monitor body temperature and provide 
warming/cooling measures as needed. 
• Hemodialysis and hemoperfusion have 
successfully shortened elimination half-life and 
led to full recovery.
• Atropine for bradycardia (0.02–0.04 mg/kg 
IM/IV/SC PRN for dogs or cats). • Antiemetics 
as needed (e.g., maropitant 1 mg/kg SC q24h). 
• Diazepam (0.25–1.0 mg/kg IV to effect) or 
midazolam (0.1–0.3 mg/kg IV/IM) for seizures; 
use lowest effective dose. • For seizures refractory 
to bolus diazepam or midazolam, use CRI of 
diazepam (0.1–0.5 mg/kg/h), midazolam 
(0.05–0.5 mg/kg/h), levetiracetam (dogs, 
30–60 mg/kg IV; cats, 20 mg/kg IV), propofol 
(1–8 mg/kg IV to effect, followed by CRI dose 
of 0.1–0.6 mg/kg IV for dogs or cats), or 
inhalant anesthesia. • Agitation may be treated 
with diazepam or midazolam; acepromazine 
(0.05–0.2 mg/kg IV/IM/SC PRN for cats or 
dogs) should be used with caution. 
• Cyproheptadine for vocalization/disorientation 
(dogs, 1.1 mg/kg PO or rectally q4–6h; cats, 
2–4 mg total dose q4–6h). • IV lipid emulsion 
(ILE) has successfully treated dogs suffering 
from baclofen intoxication; should be reserved 
for critical cases; doses vary; using 20% 
emulsion, give 1.5 mL/kg IV bolus followed by 
CRI of 0.25 mL/kg/min for 30–60 min; if 
initial bolus fails to produce desired effect, consider additional  doses of 1.5 mL/kg IV 
q4–6h for initial 24 hours; if after 3–5 boluses 
no clinical response is seen, discontinue use; do 
not exceed 8 mL/kg/day.
• Use acepromazine cautiously due to risk of 
hypotension. • Use all sedatives cautiously as 
baclofen also causes sedation. • Avoid drugs that 
cause respiratory depression (e.g., phenobarbital).
  FOLLOW-UP
• Serious cases require intense, consistent 
patient monitoring including vital signs, blood 
pressure, blood gas analysis, pulse oximetry, and 
end tidal CO2. • Nursing care should include 
turning/repositioning q6h, ocular lubrication, 
keeping patient dry/clean, passive range of 
motion of limbs, and soft bedding.
Educate pet owners about risks of leaving 
prescription drugs accessible to pets.
Aspiration pneumonia due to combination of 
vomiting, sedation, seizures, and paralysis of 
diaphragm/intercostal muscles.
• Patients suffering serious intoxications may 
take 5–7 days to fully recover. • Recovery 
often occurs with no residual effects. 
• Prognosis good with early and appropriate 
care, but becomes poor if medical care 
delayed; seizures and aspiration pneumonia 
associated with guarded prognosis.
• GABA = gamma-aminobutyric acid.
• ILE = intravenous lipid emulsion.
• PCP = phencyclidine.
http://www.petpoisonhelpline.com/poison/
baclofen
Khorzad R, Lee JA, Whelan M, et al. Baclofen 
toxicosis in dogs and cats: 145 cases 
(2004–2010). J Am Vet Med Assoc 2012, 
241(8):1059–1064.
Author  Ahna G. Brutlag
   Client Education Handout 
available  onlineBaclofen Toxicosis

164  Blackwell’s Five-Minute Veterinary Consult  
B
  BASICS
OVERVIEW
• Small, facultative, fastidious intracellular 
argyrophilic, hemotrophic Gram-negative rod 
(bacilli) bacteria. • Emerging, vector-
transmitted (fleas, ticks); adapted to reservoir 
hosts, establishes chronic, intraerythrocytic 
bacteremia. • Cats—usually asymptomatic, 
reservoir host. • Dogs—emerging clinical 
syndrome. • Seasonal—more cases reported 
between July and January. • Human syndrome—  
variable; cat scratch disease most common; 
worldwide, estimate >25,000 cases/year in 
United States; few fatalities.
SIGNS
Cats
• May have no clinical signs. • Lymphoid 
hyperplasia, uveitis, endocarditis (rare), 
self-limiting fever. • Between 5 and 60% 
seropositive, depending on geographic area.
Dogs
Nonspecific; include lethargy, fever, lymphad -
enomegaly, uveitis, or chorioretinitis, and may 
include signs consistent with endocarditis (e.g. 
weakness, cardiac arrhythmias), encephalitis 
(e.g. seizures, ataxia), myocarditis, vasculitis, 
rhinitis, angioproliferative lesions, or arthritis.
• Dogs—flea and tick exposure, rural 
environment. • Bartonella associated with 
clinical illness in dogs and cats include 
Bartonella henselae , B. clarridgeiae , 
B. koehlerae , B. quintana , B. vinsonii  ssp. 
berkhoffii , B. rochalimae , B. elizabethae . 
• Human disease associated with contact with 
cats ( >90%), particularly young cats with fleas.
  DIAGNOSIS
Other tick-borne infections ( Ehrlichia , 
Babesia ). Due to the broad spectrum of 
diseases associated with Bartonella, many 
differentials possible.
• Anemia, thrombocytopenia, eosinophilia.
• Hyperglobulinemia, signs of liver dysfunc -
tion, hypoglycemia possible.
• Serology—indirect fluorescent antibody, 
ELISA, and western immunoblot.
◦ Fourfold rise in antibody titer over a 
2–3-week period consistent with infection. ◦ Good specificity, poor sensitivity. ◦ Acutely 
ill bacteremic animals may not have 
detectable antibodies.
• PCR amplification of bacterial DNA—on 
blood, body fluids, fresh or fresh frozen 
tissue; for cases with negative culture and 
serology. • Bartonella  alpha proteobacteria 
growth medium (BAPGM) culture—of 
blood, cerebrospinal fluid, joint fluid, 
effusions, or tissue biopsies; enriched 
media, requires 14–30 days; obtain culture 
before antibiotic therapy. • Combination 
BAPGM and PCR enhances diagnostic 
sensitivity.
• Histopathology of lymph nodes—nonspecific 
inflammatory reaction: granulomas, micro  - 
abscesses, and necrosis. • Warthin–Starry 
silver stain—bacilli in lesions. 
• Immunohistochemistry, alone or with PCR 
to identify bacteria.
  TREATMENT
Supportive care.
• Optimal protocols for treating Bartonella  
spp. have not been established; likely long- 
term (4–6 weeks) antibiotics required. 
• Difficult to completely eliminate organism 
in cats; treatment reserved for symptomatic 
animals or those owned by immunocompromised 
people. • Single-agent antibiotic therapy not 
efficacious. • Antibiotic therapy: ◦ Cats—
doxycycline, amoxicillin–clavulanate, 
fluoroquinolones, and azithromycin have 
been used. ◦ Dogs—fluoroquinolone + 
doxycycline good first choice; amoxicillin, 
gentamicin/amikacin, rifampin, 
erythromycin, azithromycin also options. 
◦ Macrolides not recommended as first 
line due to rapid development of resistance.
  FOLLOW-UP
• Immunocompromised people should avoid 
young cats. • Flea prevention.
Caution with fluoroquinolones in cats and 
young dogs.  MISCELLANEOUS
• One episode appears to confer lifelong 
immunity. • Bacillary angiomatosis—vascular 
proliferative disease of skin; may be caused by 
B. henselae ; responds to antimicrobial drugs.
• Risk of transfer of organisms from infected 
dogs and cats to people unknown. • Infected 
cats likely serve as source of organisms for fleas 
that transmit infection to humans (i.e., cat 
scratch disease). • Dogs may be chronically 
infected reservoirs for Bartonella  species. 
• Veterinarians are at occupational risk of 
infection from exposure. • Human disease 
manifested as erythema followed by unilateral 
regional lymphadenopathy (painful, often 
suppurative) in 3–10 days. Infection may be 
accompanied by fever, malaise, myalgia, nausea. 
Atypical infections may result in encephalopathy, 
meningitis, palpebral conjunctivitis, endocarditis, 
hepatitis, other systemic manifestations.
• BAPGM = Bartonella  alpha proteobacteria 
growth medium.
• www.cdc.gov/bartonella/index.html
• www.abcdcatsvets.org/feline-bartonellosis
• www.galaxydx.com
Álvarez-Fernández A, Breitschwerdt EB, 
Solano-Gallego L. Bartonella infections in 
cats and dogs including zoonotic aspects. 
Parasit Vectors 2018, 11(1):624.
Lappin MR. Update on flea and tick 
associated diseases of cats. Vet Parasitol 
2018, 254:26–29.
Pultorak EL, Maggi RG, Breitschwerdt EB. 
Bartonellosis: a one health perspective. In: 
Yamada A, ed. Confronting Emerging 
Zoonoses. Tokyo: Springer, 2014, pp. 113–149.
Author  J. Paul Woods
Consulting Editor  Amie KoenigBartonellosis

Canine and Feline, Seventh Edition  165
B
Basal Cell Tumor
  BASICS
OVERVIEW
• Originates from the basal epithelial cells of 
both epidermal and adnexal origin. 
• Majority of them are benign (e.g., basal cell 
epithelioma and basaloid tumor), with 
smaller occurrences of malignant (e.g., basal 
cell carcinoma) tumors.
• Metastasis is rare with the benign forms, 
and uncommon with malignant.
• Most common skin tumor in cats (10–26%) 
and second to third most common skin tumor 
in dogs (4–12%). 
• Median age—dogs, 6–9 years; cats, 10–11 
years. 
• Cocker spaniels, Kerry blue terriers, Siberian 
huskies, English springer spaniels, and poodles 
are predisposed for dogs. Persian, British Blue, 
Norwegian Forest Cat, Himalayan, and 
Siamese are predisposed for cats.
SIGNS
• Solitary, well-circumscribed, firm, often 
hairless, intradermal raised mass, typically 
located on the head, neck, limbs, or 
shoulders. 
• Can vary greatly in size from a few milli  - 
meters to many centimeters in diameter. 
• Feline basal cell tumors are frequently 
heavily pigmented, and occasionally cystic or 
ulcerated.
• Breed (see Signalment). 
• Contrary to human basal cell tumors, 
chronic ultraviolet exposure does not appear 
to play a role in pets. 
• Possible association with papillomavirus in 
dogs and cats.
  DIAGNOSIS
• Other skin tumors including mast cell 
tumor, extramedullary plasmacytoma, 
melanoma, hemangioma, hemangiosarcoma, 
histiocytoma. 
• Melanoma is an especially important 
differential with the pigmented feline basal 
cell tumors. 
• Intradermal cysts.
Normal
N/A
IMAGING
N/ADIAGNOSTIC PROCEDURES
• Cytologic evaluation of fine-needle 
aspiration sample reveals aggregates of round 
cells with basophilic cytoplasm; mitoses are 
not uncommon despite benign nature. In 
basal cell carcinomas, mitotic activity may be 
low to high with atypical mitotic figures. 
• When clinically indicated, fine-needle 
aspiration of draining lymph nodes to confirm 
or deny the presence of regional metastases. 
• Histopathologic examination required for 
definitive diagnosis; when highly pigmented, 
immunohistochemistry occasionally required 
to differentiate from melanoma.
• Histologic cellular patterns vary from solid 
to cystic to ribbon appearance. 
• T umor cells may contain melanin pigment -
ation; may have a fine eosinophilic stroma. 
• Nuclear criteria might help predict risk of 
local recurrence in feline basal cell carcinomas.
  TREATMENT
• Surgical excision treatment of choice and 
generally curative for fully resectable tumors. 
• Cryosurgery or plesiotherapy with 
strontium-90 can be used for smaller, superficial 
lesions ( <1 cm).
N/A
N/A
  FOLLOW-UP
• Complete surgical excision is usually 
curative and associated with an excellent 
prognosis. 
• Majority of tumors are locally confined and 
nonmetastatic. Long-term follow-up is 
generally unnecessary.
T umors and tumor-like lesions. In: 
Holzworth J, ed., Diseases of the Cat: 
Saunders, 1987, pp. 406–596.Cowell RL, Tyler RD, Meinkoth JH. 
Diagnostic Cytology and Hematology of 
the Dog and Cat. St. Louis, MO: Mosby, 
1999, pp. 40–42.
Ho NT, Smith KC, Dobromylskyj MJ. 
Retrospective study of more than 9000 
feline cutaneous tumours in the UK: 
2006–2013. J Feline Med Surg 2018, 
20(2):128–134.
Ramos-Vara JA, Miller MA, Johnson GC, 
et al. Melan A and S100 protein immuno-
histochemistry in feline melanomas: 48 
cases. Vet Pathol 2002, 39:127–132.
Simeonov R, Simeonova G. Nucleomorphometric 
analysis of feline basal cell carcinomas. Res 
Vet Sci 2008, 84:440–443.
Louis-Philippe de Lorimier.

166  Blackwell’s Five-Minute Veterinary Consult  
BBattery Toxicosis
  BASICS
OVERVIEW
• Alkaline/acid-based batteries (generally 
referred to as dry cell batteries)—gastro -
intestinal tract (GIT) ulcers from leaking 
corrosive contents, oral injury from chewing 
on casing, rarely heavy metal toxicity from 
breakdown of casing in the GIT.
• Disc/button/lithium ion batteries—rapid 
necrosis to the esophagus and stomach due to 
electric current from the battery; significant 
necrosis can occur 15 minutes after contact.
Dogs, cats, birds, and small mammals. Young 
animals are more commonly affected.
SIGNS
• Historical—finding chewed-up electronic 
equipment without the battery; chewed or 
mangled battery or battery packaging.
• Black debris in the oral cavity is evidence of 
leaked dry cell battery contents.
• Physical:
◦ Oral ulcerations.
◦ Oral injury from chewing on battery 
casing.
◦ Anorexia, drooling, regurgitation, vomiting, 
diarrhea, melena, progressive weakness, 
dyspnea, coughing, stridor, pleuritis, 
pyothorax, and pneumo-mediastinum.
  DIAGNOSIS
• Diagnosis based on history, complete oral 
exam, and full (esophagus and abdominal 
GIT) survey radiographs.
(NSAIDs), foreign body obstruction (FBO), 
pancreatitis, and other corrosive compounds 
(cleaning agents, drain cleaners, pool 
shocking agents, etc.).
• Anemia—secondary to bleeding GI 
ulceration.
• Leukocytosis—inflammation and secondary 
• Elevated total proteins/prerenal azotemia—
secondary to dehydration.
• Elevated liver enzymes secondary to heavy 
metal toxicity from breakdown of casing.
IMAGING
• Full survey radiographs—determine if a 
battery was swallowed, assess location and 
condition of battery and casing; look for 
evidence of perforation and/or obstruction.• Endoscopy—pending severity of signs, 
evaluate extent of damage to esophagus; may 
be able to remove battery or casing; use 
caution and do not damage esophagus.
  TREATMENT
• Lavage oral cavity for 10–15 minutes for 
alkaline batteries; for disc batteries give 
10–20 mL of water every 15 minutes until 
battery is out of esophagus.
• Do not induce vomiting, as this may expose 
esophagus to further injury.
• NPO or slurry feeding for 24–48 hours if 
oral ulcerations are present.
• Ulceration may not be visible in the oral 
cavity until 48 hours post exposure.
• Wear gloves when cleaning up battery 
debris, as leaked acid could cause injury to 
hands.
• Small, intact dry cell batteries in stomach 
should pass within 48 hours; evaluate all 
stools and if battery has not passed the 
pylorus in 48 hours, surgical removal is 
• Punctured dry cell batteries and disc/
button/lithium ion batteries should be 
immediately removed by endoscopy or 
surgery.
• Analgesics:
◦ Dogs—butorphanol 0.1–0.5 mg/kg IV/
IM/SC; tramadol 4–10 mg/kg PO q6–8h.
◦ Cats—buprenorphine 0.01–0.03 mg/kg 
buccal/IV/IM q6–8h.
• Antiemetics—maropitant 1 mg/kg PO/SC/
IV q12h PRN.
• H2 blockers—pantoprazole 0.7–1 mg/kg 
IV over 15 min q24h; ranitidine 1–2 mg/kg 
PO/SC/IM/IV q8–12h; famotidine 0.5–
1.1 mg/kg PO q12h.
• Sucralfate 0.25–1 g PO q8h on empty 
stomach.
• Antibiotics—as needed to prevent 
secondary infection when ulcers are present.
CONTRAINDICATIONS/
POSSIBLE INTERACTIONS
• Emetics—emesis should not be performed 
as it may worsen damage to the esophagus.
• Steroids—may reduce risk of esophageal 
stricture, but expected to slow healing time.
• NSAIDs—–aid in pain management and 
swelling reduction, but may increase risk of 
gastric ulceration/perforation.  FOLLOW-UP
Consider endoscopy 2 weeks post exposure to 
assess condition of esophagus.
Esophageal perforation, esophageal stricture, 
gastrointestinal obstruction, heavy metal 
toxicity.
• Nonruptured dry cell battery—excellent; 
most pets pass on own within 48 hours.
• Ruptured dry cell battery—guarded, 
pending location of corrosive exposure and 
amount of time before removal; esophageal 
injury worsens prognosis.
• Disc/button/lithium ion battery—guarded, 
rapid removal is needed; significant injury, 
including esophageal or gastric perforation, 
can occur within 15 minutes of ingestion.
• Heavy metal toxicity.
• Esophagitis.
• Esophageal stricture.
• Esophageal perforation.
• Gastrointestinal obstruction.
• FBO = foreign body obstruction.
drug.
Angle CA. Batteries. In: Osweiler GD, Hovda 
LR, Brutlag AG, et al., eds. Blackwell’s 
Five-Minute Clinical Companion, Small 
Animal Toxicology. Ames, IA: Wiley-
Blackwell, 2016, pp. 617–623.
Yamashita M, Saito S, Koyama K, et al. 
Esophageal electrochemical burn by 
button-type alkaline batteries in dogs. Vet 
Hum Toxicol 1987, 29:226–230.
Author  Tyne Hovda
Catherine A. Angle.
available  online

Canine and Feline, Seventh Edition  167
B
Baylisascariasis
  BASICS
OVERVIEW
• Disease caused by the raccoon roundworm, 
Baylisascaris procyonis .
• T wo forms reported in dogs—intestinal 
infection occurring in adults; visceral disease 
caused by larval migration in puppies.
• Infection of raccoons occurs by ingestion 
of eggs or larvae in tissues of mammalian 
paratenic hosts.
• Dogs are infected by ingestion of infective 
eggs or paratenic hosts, from which they 
develop patent infections with adult worms in 
small intestine; puppies, probably infected by 
the ingestion of eggs, develop visceral disease.
• Dogs with intestinal infection are typically 
without signs; puppies with larval baylisasca-
riasis show signs of neurologic disease.
• Dogs.
• Intestinal form—adult animals.
• Larval form—puppies; suspect only severe 
cases have been reported; infection with only 
a few larvae probably does not cause severe 
disease in most puppies.
SIGNS
• Intestinal form—none.
• Larval form—weakness, ataxia, dysphagia, 
circling, recumbency.
Sharing space with areas frequented by raccoons.
  DIAGNOSIS
• Intestinal form—eggs in feces can be 
distinguished from those of either Toxocara  or 
Toxascaris .
• Larval form—rabies, canine distemper, 
congenital neurologic defect, other infectious 
or inflammatory neurologic disease.
Usually normal; eosinophilia has been reported.
N/A
IMAGING
• Larval form—based on lesions of toxocaria-
sis or baylisascariasis in humans, lesions may 
appear on abdominal ultrasound or CT scans 
as small, single or multiple, ill-defined, oval 
or elongated, low-attenuating lesions in liver 
parenchyma.
• In neurologic lesions, MRI reveals diffuse 
periventricular white matter disease with atrophy.
• Intestinal form—direct fecal smear or fecal 
flotation (Web Figure 1).• Larval form—ophthalmoscopic examina-
tion may show migratory tracks in retina, 
may use advanced imaging methods to 
visualize lesions in soft tissue or brain.
  TREATMENT
• Intestinal form—may treat as inpatient to 
prevent environmental contamination with 
eggs and to ensure proper disposal (as 
biohazard) or destruction (incineration) of 
fecal material and worms after treatment.
• Larval form—no treatment to date.
• Client education—alert owner of potential 
risk to people who may frequent similar 
habitats to raccoons.
Intestinal Form
• Pyrantel pamoate—5–10 mg/kg PO.
• Fenbendazole (50 mg/kg q24h PO) for 
3 days, repeat in 2 weeks.
• Febantel (25–35 mg/kg PO) with pyrantel 
pamoate (5–7 mg/kg PO) and praziquantel 
(5–7 mg/kg PO); Drontal Plus® label dose 
PO q24h for 5 days.
• Ivermectin (5  μg/kg PO) with pyrantel 
pamoate (5 mg/kg PO); Heartguard® 
approved label dosage, once monthly.
• Milbemycin (0.5–0.9 mg/kg PO), with 
lufenuron (10 mg/kg PO); Sentinel® approved 
label dosage, once monthly.
Larval Form
Corticosteroids and long-term albendazole 
(25–50 mg/kg/day PO for 10 days) may 
prove beneficial.
N/A
  FOLLOW-UP
• Intestinal form—check feces 2 weeks after 
deworming and again 1 month later.
• Larval form—disease has proven fatal.
• Intestinal form—eggs are not infectious 
when passed, but can develop in the 
environment in several days; ingestion of eggs 
containing infective larvae by humans can 
cause severe disease, i.e., larval baylisascariasis.• Larval form—infected puppies pose no 
zoonotic threat.
• Alert owner of potential risk to people who 
may frequent similar habitats to raccoons.
Bauer C. Baylisascariosis—infections of 
animals and humans with “unusual” 
roundworms. Vet Parasitol 2013, 
193:404–412.
Kazacos KR. Baylisascaris  Larva Migrans. US 
Geological Survey, Circular 1412, 2016. 
doi: 10.3133/cir1412
Rowley HA, Uht RM, Kazacos KR, et al. 
Radiologic-pathologic findings in raccoon 
roundworm ( Baylisascaris procyonis ) 
encephalitis. Am J Neuroradiol 2000, 
21:415–420.
Author  Dwight D. Bowman

168  Blackwell’s Five-Minute Veterinary Consult  
BBenign Prostatic Hyperplasia
  BASICS
OVERVIEW
• Age-related pathologic change in prostate 
gland, making it nonpainfully large.
• Occurs in two phases, glandular and complex.
• Glandular phase characterized by high 
number of large prostatic cells and symmetri -
cally large prostate gland.
• Complex phase characterized by glandular 
hyperplasia and atrophy, small cyst formation, 
chronic inflammation, and squamous 
metaplasia of epithelium.
Prevalence increases with age; 60% of intact 
male dogs affected by 6 years and 95% of 
intact male dogs affected by 9 years of age.
SIGNS
• None in most dogs.
• Serosanguinous urethral discharge.
• Hemospermia.
• Hematuria.
• Dysuria.
• Dyschezia.
• Ribbon-like stools.
• Symmetric, nonpainfully enlarged prostate 
gland.
• Prostatic pain in dogs with complication of 
bacterial infection or prostatic carcinoma.
• Dihydrotestosterone (DHT; strongly) and 
testosterone (weakly).
• Aging as intact male.
• Risk eliminated by castration.
  DIAGNOSIS
• Acute bacterial prostatitis—fever, 
depression, pain on rectal palpation, neutro  - 
philia, pyuria, and bacteriuria; occurs 
concurrently with and secondary to benign 
prostatic hyperplasia (BPH).
• Chronic bacterial prostatitis—recurrent lower 
urinary tract infections and subfertility; occurs 
concurrently with and secondary to BPH.
• Prostatic adenocarcinoma—poor appetite, 
weight loss, hind limb weakness, dysuria, 
hematuria, and dyschezia; may see carcinoma 
cells in urine sediment.
• Prostatic and paraprostatic cysts—can cause 
palpable abdominal cystic mass filled with 
yellow to orange fluid.CBC/BIOCHEMISTRY/URINALYSIS
• CBC and biochemistry—normal in BPH.
• Urinalysis—may be normal or reveal 
hematuria; pyuria and bacteriuria absent 
unless concurrent bacterial infection.
Elevated serum concentration of canine 
prostate-specific arginine esterase correlates 
with histologic evidence of BPH.
IMAGING
• Radiography—abdominal radiographs 
reveal prostatomegaly.
• Ultrasonography—reveals enlarged prostate 
gland with uniform prostatic parenchymal 
echogenicity; small, fluid-filled cysts.
Prostatic fluid obtained by ejaculation or 
prostatic massage may be clear or hemorr -
hagic; red blood cell count high; white blood 
cell count normal; culture reveals <100,000 
colony-forming units of bacteria/mL unless 
dog has concurrent bacterial infection.
  TREATMENT
• Not required if asymptomatic.
• Castration—most effective and prevents 
recurrence; if BPH complicated by acute 
bacterial prostatitis, delay surgery until 
infection resolved.
• Finasteride, if castration not desired, as long 
as dog is to remain intact.
• If castration not acceptable, the 
following are the most available and 
clinically useful:
◦ Finasteride (0.1 mg/kg/day, not to exceed 
5 mg/dog/day) for as long as dog remains 
intact—inhibits conversion of testosterone 
to DHT by enzyme 5- α-reductase.
◦ Osaterone acetate (0.25 mg/kg PO once 
daily for 7 days)—competitively binds to 
androgen receptors, reduces 5- α-reductase, 
inhibits testosterone transport into 
prostate cells.
◦ Delmadinone acetate (3 mg/kg SC 
once)—antiandrogenic activity due to 
competitive binding to androgen receptors.
◦ Deslorelin acetate (subcutaneous implant 
administered every 6–12 months)— 
gonadotropin-releasing hormone (GnRH) 
agonist to inhibit hypothalamic–pituitary–
gondal axis by negative feedback.CONTRAINDICATIONS/POSSIBLE 
• Potential for glucocorticoid insufficiency 
during stressful events for unspecified period 
after delmadinone acetate treatment.
• GnRH agonists contraindicated in breeding 
dogs as will inhibit fertility.
  FOLLOW-UP
• Castration is treatment of choice for 
nonbreeding dogs, will result in 80% 
reduction in prostate volume within 12 
weeks.
• Finasteride is treatment of choice for 
breeding males. Side effects in dogs reported. 
Prostate reduced 50–70% between 16 and 
53 weeks of treatment. Testosterone preserved, 
thus finasteride not associated with decline in 
libido or semen quality. BPH will recur after 
withdrawal of finasteride; time until clinical 
signs recur is variable.
• Bacterial prostatitis and prostatic 
carcinoma.
• Prostatomegaly in castrated dog strongly 
suggests prostatic carcinoma, as other 
prostatic diseases unlikely to occur in absence 
of androgenic influence.
SEE ALSO
• Prostatic Cysts.
• Prostatomegaly.
• BPH = benign prostatic hyperplasia.
• DHT = dihydrotestosterone.
• GnRH = gonadotropin-releasing hormone.
Christensen, BW. Canine prostate disease. Vet 
Clinics North Am Small Anim Pract 2018, 
48(4):701–719.
Smith J. Canine prostatic disease: a review of 
anatomy, pathology, diagnosis, and treatment. 
Theriogenology 2008, 70:375–383.
Author  Bruce Christensen
Acknowledgments  The author and book 
of Carl A. Osborne and Jeffrey S. Klausner.

Canine and Feline, Seventh Edition  169
B
Benzodiazepine and Other Sleep Aids Toxicosis
  BASICS
• Toxicosis due to ingestion of sleep aids or 
antianxiety medications commonly used in 
human and veterinary medicine.
• Benzodiazepine class—alprazolam (Xanax®), 
clonazepam (Klonopin®), diazepam (Valium®), 
lorazepam (Ativan®), midazolam (Versed®), 
temazepam (Restoril®), triazolam (Halcion®), 
and many more.
• Imidazopyridine class—eszopiclone 
(Lunesta®), zaleplon (Sonata®), and zolpidem 
(Ambien®, Ambien CR, Intermezzo®, 
Zolpimist®).
• Benzodiazepines and imidazopyridines bind 
to receptors near the gamma-aminobutyric 
acid (GABA) receptor/chloride channel on 
neurons; they potentiate GABA’s effect, which 
increases the opening of the chloride channel, 
leading to hyperpolarization of the nerve and 
decreased excitation.
• Imidazopyridines bind near the receptor 
subset that is responsible for sedation, while 
benzodiazepines bind to all receptor subsets 
and so not only mediate sedation, but are also 
anticonvulsant and anxiolytic.
• Paradoxical reactions can occur and are 
typically described as excitement, irritability, 
and aberrant demeanor in cats and excitement 
in dogs, when the expected effect is seizure 
control or sedation.
• Both classes are well absorbed orally and 
have rapid onset of actions, often less than 30 
minutes.
• Duration of action depends on the drug 
and may last for hours to days.
• Both classes have wide margins of safety; 
lethal exposures are rare if a single agent is 
involved.
• Benzodiazepines—signs can be seen at 
therapeutic doses; however, the drugs have a 
wide margin of safety, with the minimal lethal 
dose being approximately 1,000 times the 
therapeutic dose. Cats may develop idiosyn -
cratic hepatic failure with chronic oral dosing 
of diazepam and clonazepam.
• Zaleplon—based on a review of the 
American Society for the Prevention of 
Cruelty to Animals’ Animal Poison Control 
Center (ASPCA APCC) Antox database: in 
dogs, doses >0.11 mg/kg have been associated 
with restlessness and hyperactivity; in cats, 
doses of >1.25 mg/kg caused paradoxical 
reactions.
• Zolpidem—based on a review of the 
ASPCA APCC Antox database: in dogs, 
dosages >0.2 mg/kg can cause mild sedation 
and ataxia; doses >0.6 mg/kg can cause 
paradoxical reactions. In cats, signs of paradoxical reactions were seen at 0.34 mg/kg 
or greater.
• Gastrointestinal—vomiting.
• Hepatic—acute necrosis and failure in cats 
with diazepam and clonazepam.
• Nervous—CNS depression and/or 
paradoxical reactions, ataxia, coma.
• Respiratory—depression.
GENETICS
N/A
Commonly prescribed drugs, so exposure is 
common.
None
Species
Dogs and cats—acute toxicity; cats—
idiosyncratic hepatic failure with chronic oral 
dosing of diazepam or clonazepam possible.
None
None
None
SIGNS
• Benzodiazepines can cause sedation with 
virtually any exposure (even at therapeutic 
doses).
• Imidazopyridines cause sedation at low 
doses, but likelihood of paradoxical reaction 
increases with increasing dose, especially in 
dogs.
• Evidence of accidental ingestion of 
• Therapeutic use of drug.
• Ataxia.
• Sedation.
• Ataxia.
• Hyperthermia (secondary to agitation).
• Icterus (in cats with idiopathic liver failure).
CAUSES
Accidental exposure, inappropriate admini -
stration, or therapeutic use.
• Younger and older animals.
• Animals with preexisting conditions.  DIAGNOSIS
• CNS depression—barbiturates, ivermectin, 
ethylene glycol, alcohols (e.g., ethanol, 
methanol), marijuana, opioids, and anti -
depressants (low doses).
• Paradoxical reactions—amphetamines, 
pseudoephedrine, methylxanthines, cocaine, 
phenylpropanolamine, and serotonin 
syndrome (secondary to antidepressants).
• No abnormalities expected in acute 
overdoses.
• In cats with idiopathic liver failure, elevated 
liver enzymes and bilirubin.
• Benzodiazepines can be detected in blood, 
urine, and liver; over-the-counter (OTC) 
drug-testing kits may be used to confirm 
exposure, but the label should be examined 
closely to be certain all benzodiazepines are 
included in the test kit.
• Imidazopyridines can be detected in blood 
and urine; OTC drug-testing kits are not yet 
readily available.
N/A
No gross or histologic changes are expected.
  TREATMENT
• Outpatient—most mildly affected animals 
can be managed at home with confinement 
(to avoid injury due to falls) and minimizing 
stimulation.
• Inpatient—animals who are comatose or 
showing paradoxical reactions.
• Intravenous fluids.
• Monitor and control body temperature.
• Good bedding and frequent turning for 
recumbent patients.
• Minimize sensory stimulation, especially 
with paradoxical reactions.
ACTIVITY
Restrict until recovered to avoid injury.
DIET
Cats with liver failure may require forced or 
tube feeding for support.
• Make all clients aware of proper storage of 
all medications.
• If prescribing diazepam or clonazepam to 
cats, have owner closely monitor the cat for 
the first week.

170  Blackwell’s Five-Minute Veterinary Consult  
B
N/A
• Acepromazine 0.01–0.2 mg/kg IV/IM as 
needed to control paradoxical reactions.
• Cyproheptadine 1.1 mg/kg PO q4–6h or 
rectally for dogs; 2–4 mg/cat q4–6h for 
control of paradoxical reactions.
• Flumazenil—a benzodiazepine reversal 
agent: 0.01 mg/kg IV q1–2h as needed; it can 
be used to reverse both excessive sedation and 
paradoxical reaction; however, flumazenil can 
cause seizures, so its use is generally restricted 
to life-threatening situations.
Do not give other benzodiazepines to control 
paradoxical reactions.
N/A
Care when using other depressant medic -
ations (e.g., barbiturates, phenothiazines), as 
these can potentiate the depressant effects of 
these drugs.
  FOLLOW-UP
TPR, blood pressure, respiratory effort.PREVENTION/AVOIDANCE
Secure medications out of reach of dogs and 
cats.
No long-term complications expected.
• Prognosis for acute overdose is excellent 
with symptomatic care.
• Prognosis for acute hepatic failure in cats 
with diazepam is poor.
N/A
• Young animals and those with preexisting 
liver disease may have prolonged signs due to 
reduced ability to clear the drugs.
• Younger animals may be more prone to 
None
Benzodiazepines are considered teratogenic.
SEE ALSO
• Amphetamine and ADD/ADHD 
Medication Toxicosis.
SNRIs.
• Antidepressant Toxicosis—T ricyclic.
• Ethanol Toxicosis.• Ethylene Glycol Toxicosis.
• Ivermectin and Other Macrocyclic Lactones 
Toxicosis.
• ASPCA APCC = American Society for the 
Prevention of Cruelty to Animals’ Animal 
Poison Control Center.
• OTC = over-the-counter.
• http://www.aspca.org/pet-care/
• http://www.petpoisonhelpline.com/poison/
lunesta
Center SA, Elston TH, Rowland PH, et al. 
Fulminant hepatic failure associated with 
oral administration of diazepam in 11 cats. 
J Am Vet Med Assoc 1996, 
209(3):618–625.
Czopowicz M, Szalus-Jordanow O, Frymus T. 
Zolpidem poisoning in a cat. Aust Vet J 
2010, 88(8):326–327.
Lancaster AR, Lee JA, Hovda LR, et al. Sleep 
aid toxicosis in dogs: 317 cases (2004–2010). 
J Vet Emerg Crit Care 2011, 21(6):658–665.
Author  Eric K. Dunayer
Consulting Editor  Lynn R. HovdaBenzodiazepine and Other Sleep Aids Toxicosis  (continued)

Canine and Feline, Seventh Edition  171
B
Beta Receptor Antagonist (Beta Blockers) Toxicosis
  BASICS
OVERVIEW
• Beta receptor antagonists—class II anti  - 
dysrhythmics used to treat hypertrophic or 
hypertrophic obstructive cardiomyopathy in 
cats and hypertension and tachydysrhythmias 
in dogs and cats.
• β1 receptors—primarily located in heart, 
eye, and kidney.
• β2 receptors—primarily located in bronchial 
smooth muscle, gastrointestinal tract, pancreas, 
liver, skeletal muscle, vascular smooth muscle, 
and endothelium.
• Systems affected include:
◦ Cardiovascular—bradycardia, hypotension.
◦ Respiratory—bronchospasm.
◦ Nervous—decreased mentation, seizures.
◦ Endocrine/metabolic—hypoglycemia, 
metabolic acidosis secondary to hypo- 
◦ Renal/urologic—acute kidney injury 
secondary to prolonged hypoperfusion.
Dogs and cats equally affected with no breed, 
age, or sex predilection.
SIGNS
• Bradycardia, atrioventricular (AV) block.
• Decreased mentation.
• Respiratory distress/bronchospasm.
• Coma.
• Death.
Therapeutic overdose or ingestion of 
  DIAGNOSIS
• Calcium channel blocker overdose.
• Cardiac disease with bradyarrhythmias.
• Cardiovascular drug overdose (e.g., 
clonidine, digoxin toxicosis).
• Sedative overdose (e.g., opioid or baclofen 
toxicosis).
• Sick sinus syndrome.
• Decompensated shock.
• Hyperkalemia (mild).
• Azotemia and elevated liver enzymes with 
prolonged hypoperfusion.
Blood gas—metabolic acidosis.DIAGNOSTIC PROCEDURES
• ECG—first, second, and third degree AV 
block; prolonged PR, QRS, and QT intervals.
• Echocardiogram—negative inotropy, 
decreased cardiac output.
  TREATMENT
• Emesis if asymptomatic and recent 
ingestion (<2 hours).
• Consider gastric lavage if decreased mental 
status and large number of pills ingested.
• Volume resuscitation with IV fluid bolus 
over 15–20 minutes for hypotension—cats, 
10–20 mL/kg for cats; dogs, 20–30 mL/kg.
• Consider temporary cardiac pacing and 
hemodialysis (drug removal) in severe 
intoxications.
• Activated charcoal (1–2 g/kg) within 2 
hours post exposure; repeat activated charcoal 
for ER formulations.
• Atropine (0.02–0.04 mg/kg IV) for sinus 
• Intravenous fat emulsion (IFE)—may bind 
lipid-soluble drugs, increase Ca available for 
muscle contraction, and provide energy source 
for heart muscle. IFE 20% dose—1.5 mL/kg 
IV bolus over 1 min followed by CRI of 
0.25 mL/kg/min for 30–60 min. Additional IV 
doses—1.5 ml/kg every 4–6 hours or CRI of 
0.5 mL/kg/h; monitor serum for lipemia every 
2–4 hours to determine if additional dosing 
needed.
• High-dose insulin euglycemia (HIE) 
treatment—may provide energy for heart 
muscle and increase Ca available for muscle 
contraction. Recommended treatment:
◦ Check blood glucose (BG) concentration 
and administer dextrose if BG <100 mg/dL.
◦ Administer regular insulin at 1 unit/kg IV 
followed by CRI at 0.5–2 units/kg/h. Increase 
every 10 min as needed up to maximum dose 
of 10 units/kg/h. When clinical signs resolve, 
decrease insulin by 1–2 units/kg/h.
◦ Monitor BG every 10 min while titrating 
insulin dosing. Once insulin dosing is 
stabilized, check BG every 30–60 min. 
Dextrose supplementation IV will be needed 
to maintain normal BG concentrations. 
Central line placement recommended for 
frequent glucose monitoring and dextrose 
administration during HIE treatment. May 
need to continue dextrose supplementation up 
to 24 hours after discontinuation of insulin.
◦ Monitor potassium concentration every hour 
during titration, then every 6 hours. Administer potassium chloride to keep potassium 
concentrations within normal range.
• Calcium gluconate 10% 0.5–1.5 ml/kg IV 
over 10–20 min, followed by CRI 0.1–
0.15 ml/kg/h. May increase calcium available 
for heart muscle contraction.
• Glucagon—0.05–0.2 mg/kg slow IV bolus 
followed by CRI of 0.1–0.15 mg/kg/h. May 
not be as effective as IFE or HIE therapy.
• Sympathomimetics or vasopressin should only 
be used in cases refractory to other treatments.
CONTRAINDICATION/POSSIBLE 
Vasopressors/sympathomimetics may not be 
as effective as other therapy and may make 
patients less responsive to treatment.
  FOLLOW-UP
• Monitor for 8 hours with immediate release 
preparations and 12–24 hours for extended 
release (ER) preparations.
• Heart rate/ECG.
• Blood pressure.
• Potassium levels.
• Blood glucose.
Renal failure can occur secondary to 
• Ingestion of immediate release preparations 
typically result in clinical signs in 6 hours.
• Sustained release (SR) or ER preparations may 
take 12–24 hours for clinical signs to develop.
• Prognosis depends on dose ingested and 
response to therapy, but generally good.
• BG = blood glucose.
• ER = extended release.
• HIE = high-dose insulin euglycemia.
• SR = sustained release.
Engebretsen KM, Kaczarek KM, Morgan J, 
Holger JS. High dose insulin therapy in 
beta-blocker and calcium channel-blocker 
poisoning. Clin Toxicol 2011, 49(4):277–283.
Author  Katherine L. Peterson

172  Blackwell’s Five-Minute Veterinary Consult  
BBeta-2 Agonist Inhaler Toxicosis
  BASICS
OVERVIEW
• Beta-2 agonist inhaler toxicosis occurs 
when dogs chew and puncture pressurized 
inhalers containing albuterol (salbutamol), 
levalbuterol, or salmeterol.
• Loss of beta-2 adrenergic selectivity with 
overdose results in beta-1 stimulation (sinus 
tachycardia). Failure of the myocardium to 
effectively oxygenate during extreme periods 
of tachycardia can result in other tachyarrhy -
thmias such as ventricular premature 
contractions (VPCs) and ventricular 
tachycardia.
• Generalized adrenergic stimulation 
releases catecholamines that exacerbate 
cardiovascular (CV) stimulation, stimulate 
the CNS and respiratory systems, and can 
result in significant intracellular trans -
location of potassium and phosphorus.
• Propellants are now hydrofluoroalkanes 
(HFAs) and are expected to sensitize the 
myocardium less to catecholamines than older 
chlorofluorocarbon propellants.
• Behavioral—hyperactivity, apprehension, 
nervousness, restlessness.
• Cardiovascular—sinus tachycardia, other 
tachyarrhythmias.
• Endocrine/metabolic—hypokalemia, 
hypophosphatemia.
• Gastrointestinal—mild vomiting.
• Musculoskeletal—tremors, weakness with 
catecholamine depletion.
• Nervous—anxiety, apprehension 
initially, depression with catecholamine 
• Neuromuscular—tremors.
Young dogs are overrepresented due to their 
predilection for dietary indiscretion.
SIGNS
• Tachycardia, other tachyarrhythmias.
• Lethargy, weakness, depression.
• Hyperactivity, apprehension, nervousness, 
restlessness.
• T remors.
• Puncture of inhalers containing beta-2 
agonists.
• Pets prone to dietary indiscretion with 
access to inhalers.  DIAGNOSIS
• Amphetamines and related drugs such as 
those used for attention deficit hyperactivity 
disorder (ADHD).
• Sympathomimetics (e.g., phenylpropano -
lamine, pseudoephedrine, phenylephrine, 
ephedrine).
• Methylxanthines (e.g., caffeine, theobromine).
• Illicit drugs including methamphetamine.
• Thyroxine.
• Hops ( Humulus lupulus ).
• Hypophosphatemia.
ECG to confirm, monitor for arrhythmias.
  TREATMENT
• Inpatient treatment—initiate medical 
management and emergency care as soon as 
possible following exposure.
• Nursing care required—fluid support.
• Altered activity—cage rest, quiet environment.
• NPO if vomiting.
• Discuss with owner timing of presentation 
relative to exposure; patients that have 
delayed presentation and prolonged, 
untreated CNS and CV stimulation may be 
at greater risk for more serious arrhythmias 
and slower recovery.
• No surgical or anesthetic considerations.
• Benzodiazepines PRN for anxiety, nervousness, 
tremors—diazepam: 0.5–1 mg/kg IV or 1 mg/
kg rectally, repeat PRN; midazolam: 0.1–
0.3 mg/kg IV, IM, repeat PRN.
• Beta blockers for severe tachycardia (HR 
>160 in large dogs; >200 in miniature breeds), 
hypokalemia—propranolol (preferred, nonspecific 
blocker): dogs, 0.02–0.06 mg/kg IV to effect; 
esmolol (blocks beta-1 only; ultra-short acting): 
dogs, 0.25–0.5 mg/kg IV as slow bolus then 
CRI of 0.01–0.2 mg/kg/min.
• Potassium chloride supplementation—up 
to 0.5 mEq potassium/kg/h IV maximum, 
based on degree of hypokalemia.• Potassium phosphate if phosphorus <1 mg/
dL—0.01–0.03 mM/kg/h IV.
• Lidocaine for ventricular arrhythmias—
dogs, 2–4 mg/kg IV (max 8 mg/kg over 1–2 
mins) followed by CRI of 25–100  μg/kg/min; 
cats, 0.25–0.5 mg/kg IV slowly (special 
caution for use in cats due to predilection for 
CNS and CV toxicity).
N/A
  FOLLOW-UP
• Electrolytes (potassium, phosphorus) q12h 
or PRN if ECG changes, weakness (potassium), 
hemolysis (phosphorus). Note: Monitor for 
rebound hyperkalemia.
• ECG.
• Mentation.
• Rarely fatal. Persistent, severe tachycardia 
can result in myocardial hypoxia and more 
serious arrhythmias or other cardiac sequelae.
• Catecholamine depletion can result in weakness 
and depression once the stimulatory effects wane.
Excellent prognosis with prompt and appropriate 
treatment in an otherwise healthy patient.
• Albuterol crosses the placenta. Overdose 
effects are expected to be similar for the fetus. 
Hypoxia with cardiac compromise in the 
bitch may harm the fetus.
• No adverse effects expected with regard to 
fertility.
disorder.
• HFA = hydrofluoroalkane.
• VPC = ventricular premature contraction.
Mensching D, Volmer PA. Breathe with ease 
when managing beta-2 agonist inhaler 
toxicoses in dogs. Vet Med, 2007, 
June:369–373.
Author  Lynn R. Hovda
Donna Mensching.

Canine and Feline, Seventh Edition  173
BBile Duct Carcinoma
  BASICS
OVERVIEW
• Epithelial neoplasia that arises from the 
cells lining the biliary ducts or gallbladder.
• Second most common malignant hepatic 
tumor in dogs, representing 22–41% of all 
malignant canine liver tumors. • Most 
common malignant hepatobiliary tumor in 
cats, but less common than benign biliary 
cystadenoma. • Benign biliary cystadenomas 
may undergo malignant transformation into 
cystadenocarcinomas, although time period over 
which this occurs is unknown. • Common 
metastatic sites include lungs, regional lymph 
nodes, and peritoneum (carcinomatosis); other 
metastatic sites include intestine, pancreas, 
heart, spleen, kidney, spinal cord, urinary 
bladder, bone, and rarely bone marrow.
• Dogs and cats. • Possible predilection for 
Labrador retrievers. • Affected animals 
typically >10 years of age. • Possible 
predisposition for female dogs.
SIGNS
• Anorexia. • Lethargy. • Weight loss.
• Vomiting. • Polyuria/polydipsia. • Icterus.
• Abdominal distension.
• Hepatomegaly/cranial abdominal mass 
effect. • Ascites. • Icterus. • Paraneoplastic 
alopecia (ventral abdomen) associated with 
feline biliary carcinoma.
• Potential association between canine 
cholangiocarcinoma and trematode 
 (hookworms, whipworms) infection. 
• Canine biliary carcinoma has been 
experimentally induced by 
N-ethyl-N ′-nitro-N-nitrosoguanidine.
  DIAGNOSIS
• Hepatocellular adenoma (hepatoma).
• Hepatocellular carcinoma. • Biliary 
adenoma/cystadenoma. • Nodular hyperplasia.
• Cirrhosis. • Chronic active hepatitis.
• Hepatic myelolipoma. • Carcinoids.
• Anemia. • Leukocytosis. • Elevated serum 
enzyme (alkaline phosphatase [ALP], 
gamma-glutamyl transferase [GGT], alanine 
aminotransferase [ALT], aspartate 
 aminotransferase [AST]) activity. 
• Hyperbilirubinemia.OTHER LABORATORY TESTS
• α-fetoprotein (an oncofetal glycoprotein) is 
elevated in 55% of dogs with bile duct 
carcinoma; may differentiate neoplastic from 
non-neoplastic lesions in dogs. • Coagulation 
profile (prothrombin time [PT], partial 
thromboplastin time [PTT]) recommended 
before biopsy or surgical procedures. 
• Pre- and postprandial bile acids can help 
assess hepatobiliary function.
IMAGING
• Abdominal radiography—may localize a 
mass to the liver, show displacement of the 
stomach, or demonstrate loss of detail in 
patients with peritoneal effusion. • Abdominal 
ultrasonography—can be used to assess 
location and character of lesion, detect and 
sample peritoneal effusion, and guide tumor 
biopsy. • Thoracic radiography—should be 
used to screen for pulmonary metastasis.
• CT and MRI—more sensitive techniques 
that are more likely to detect smaller lesions 
not visible on ultrasound and radiography.
• Abdominocentesis and cytologic evaluation 
of peritoneal fluid. • Cytology or needle core 
(T ru-Cut®) biopsy samples via ultrasound 
guidance. • Laparoscopy or laparotomy may 
be needed to obtain larger samples for 
• Gross findings—morphologic types include 
massive (37–46%), nodular (0–21%), or 
diffuse (17–54%). Can be intrahepatic (most 
common in dogs), extrahepatic, or within the 
gall bladder (rare). • Histopathology 
findings—histologic subtypes include solid 
(cholangiocarcinoma) and cystic (biliary 
cystadenocarcinoma); subtype does not 
influence prognosis; immunohistochemistry 
(hepatocyte paraffin-1 and Claudin-7) can 
distinguish poorly differentiated hepatocel-
lular carcinoma from biliary carcinoma.
  TREATMENT
• Complete surgical excision is treatment of 
choice; surgery not applicable for nodular/
diffuse forms. • Up to 80% of liver can be 
resected if remaining liver tissue is functional.
• Interventional techniques (chemoemboliza-
tion) may be utilized as palliative procedures 
for nonresectable solitary tumors.
• Chemotherapy—no effective protocol 
identified. Tyrosine kinase inhibitors have 
been used anecdotally.CONTRAINDICATIONS/POSSIBLE 
Medications requiring metabolism by 
hepatobiliary system should be used with 
caution if evidence of dysfunction is present.
  FOLLOW-UP
Periodic physical examination, lab work, 
abdominal ultrasonography, and thoracic 
radiography after tumor resection.
Anthelmintic therapy is warranted due to 
potential association between canine bile duct 
carcinoma and infection with hookworms or 
whipworms.
• T umor rupture/hemorrhage, esp. if the 
massive form. • Biliary obstruction.
• Aggressive tumor with a guarded to poor 
prognosis, especially if nonresectable. • High 
rate of metastasis (up to 88%) in both dogs 
and cats; widespread intraperitoneal carcino  - 
matosis common in cats. • Most patients die 
within 6 months of surgery due to local 
recurrence or metastasis.
Chemotherapy drugs may be carcinogenic 
and mutagenic.
• PT = Prothrombin time. 
• PTT = Partial thromboplastin time.
Kinsey JR, Gilson SD, Hauptman J, et al. 
Factors associated with long-term survival in 
dogs undergoing liver lobectomy for liver 
tumors. Can Vet J 2015, 56:598–604.
Liptak JM. Hepatobiliary tumors. In: 
Withrow SJ, Vail DM, eds., Small Animal 
Clinical Oncology, 5th ed. St. Louis, MO: 
Saunders Elsevier, 2013, pp. 405–410.
Selmic LE. Hepatobiliary neoplasia. Vet Clin 
Small Anim Pract 2017, 47:725–735.
Authors  Christine Mullin and Craig A. 
Clifford

174  Blackwell’s Five-Minute Veterinary Consult  
B
  BASICS
Extrahepatic bile duct obstruction (EHBDO) 
is biliary tree obstruction at the level of either 
the common bile duct (CBD) or the hepatic 
ducts, where it may involve one, several, or all 
hepatic ducts. Obstruction may be partial or 
complete.
• EHBDO caused by abnormalities within 
biliary system or secondary to diseases affecting 
organs surrounding biliary tree; see Causes.
• Serious hepatobiliary injury follows within 
weeks of complete duct obstruction.
• Gallbladder (GB) bile may become colorless 
(white bile) if canalicular green pigmented 
hepatic bile not diverted into GB.
• Increased risk of bacterial infection of bile 
with stasis of bile flow.
• EHBDO progresses to biliary cirrhosis 
within 6 weeks; exception is pancreatitis 
causing EHBDO that may self‐resolve within 
2–3 weeks.
Hepatobiliary
Species
Breed Predilection
• Some breeds predisposed to pancreatitis, 
choleliths, GB mucocele (GBM), dyslipi  - 
demias.
• Animals with large duct ductal plate 
malformation (DPM) phenotypes—predis-
posed to infection and cholelithiasis.
• Choleliths appear more common in small‐
breed dogs and cats.
• Neoplasia involving CBD more common in 
older animals and cats with chronic inflam-
mation of biliary tree.
Middle‐aged to old animals with acquired 
disease; younger animals with DPM.
None
SIGNS
• Depend on underlying disorder and 
“completeness” of EHBDO.
• Progressive lethargy and vague illness 
associated with progressive jaundice.
• Pale (acholic) stools—complete EHBDO in 
absence of enteric bleeding.
• Polyphagia—complete EHBDO causes 
nutrient malassimilation (fat).
• Bleeding tendencies—within 10 days of 
complete EHBDO, more severe/overt in cats.Physical Examination Findings
• Depend on underlying cause.
• Severe jaundice.
• Hepatomegaly unless biliary cirrhosis.
• Cranial mass effect—extrahepatic biliary 
structures (small dogs and cats) or pancreatic 
• Vague cranial abdominal discomfort.
• Acholic feces—unless enteric bleeding 
(hemoglobin pigment evolves pigmented feces).
• Bleeding tendencies and bruising—chronic 
EHBDO.
• Orange urine—severe bilirubinuria.
• Diverse primary disorders.
• Choledochitis.
• Bile duct malformations—DPM pheno-
types: choledochal cysts (cats), Caroli’s 
malformation (dogs, cats), rare cystadenoma 
encroaching on porta hepatis (cats).
• Parasitic infestation—flukes (cats).
• Extrinsic compression—lymph nodes, 
neoplasia, pancreatitis, CBD entrapment in 
diaphragmatic hernia; foreign body 
obstruction of sphincter of Oddi in 
duodenum.
• Duct fibrosis—trauma, peritonitis, 
pancreatitis; major duct involvement in feline 
cholangitis/cholangiohepatitis syndrome 
(CCHS).
• Duct stricture—blunt trauma, iatrogenic 
surgical manipulations, e.g., after cholecystec- 
tomy.
  DIAGNOSIS
• Mass lesions—primary or metastatic 
hepatobiliary neoplasia; adjacent viscera.
• Diffuse infiltrative liver disease—
neoplastic, inflammatory, hepatic lipidosis 
(HL), amyloid (rare).
• Infectious hepatitis—bacterial, viral, 
trematodes, protozoal.
• Severe hepatic fibrosis/cirrhosis.
• Decompensated chronic hepatitis.
• Copper‐associated hepatopathy.
• Fulminant hepatic failure.
• Biliary cysts—DPM phenotypes: chole-
dochal (cats), cystadenoma compressing CBD 
at porta hepatis.
• Pancreatitis—CBD stenosis/stricture, 
choleliths in cats: fused bile and pancreatic 
ducts.
• HL—cats: canalicular collapse causes 
jaundice.
• CCHS—cats, lymphocytic sclerosing or 
destructive cholangitis.CBC/BIOCHEMISTRY/URINALYSIS
CBC
• Anemia—mild nonregenerative (chronic 
disease) or regenerative (enteric bleeding, 
Heinz body hemolysis).
• Microcytosis—uncommon.
• Leukogram—variable, neutrophilic 
leukocytosis, left‐shifted leukogram with 
sepsis.
• Plasma—markedly jaundiced.
• Liver enzymes—variable; marked increases 
in alkaline phosphatase (ALP) and gamma 
glutamyltransferase (GGT) reflect ductal 
injury; high alanine aminotransferase (ALT) 
and aspartate transaminase (AST) reflect 
periportal hepatocyte injury or multifocal 
injury associated with sepsis.
• Total bilirubin—moderate to markedly 
high; less than observed with hemolysis or 
HL; hyperbilirubinemia markedly escalated 
subsequent to blood transfusion.
• Albumin—variable, usually normal 
except when EHBDO >6 weeks (biliary 
cirrhosis); low albumin reflects synthetic 
failure or loss into abdominal effusion if 
syndrome complicated by GB rupture, 
suppurative hepatitis, or hepatic fibrosis 
leading to ascites.
• Globulins—normal or increased.
• Glucose—normal or low if biliary cirrhosis 
or sepsis; high if diabetes with pancreatitis.
• Hypercholesterolemia—common.
• Bilirubinuria and bilirubin crystal 
• Absence of urobilinogen—unless enteric 
bleeding; unreliable test for EHBDO.
• Serum bile acids—always markedly 
increased; superfluous test if hepatobiliary 
jaundice already suspected.
• Coagulation abnormalities—within 10 days 
of EHBDO develop vitamin K deficiency; 
may develop disseminated intravascular 
coagulation (DIC).
• Fecal examination—acholic stools consistent 
with EHBDO, but may be masked by 
small‐volume melena; trematode eggs may be 
verified in fluke infestation (cats).
IMAGING
• Abdominal radiography—inconsistent 
hepatomegaly; variable mass effect in area of 
gallbladder or CBD, pattern consistent with 
pancreatitis, mineralized cholelith(s).
• Cholecystography—rarely provides 
additional practical information.
• Abdominal ultrasonography—evidence of 
obstruction in 72–96 hours (distended, 
tortuous CBD, cystic duct, intrahepatic bile 
ducts); may disclose underlying or primary 
disorder (e.g., pancreatitis, cystic lesions, mass Bile Duct Obstruction (Extrahepatic)

Canine and Feline, Seventh Edition  175
B
B
lesions, choleliths). Caution : GB bile “sludge” 
and full GB common in anorectic or fasted 
patients—do not mistake for EHBDO.
• Caution : Feline CBD serpiginous compared 
to canine—always inspect liver image for 
distended intrahepatic bile ducts and confirm 
that “tubes” are ducts rather than vasculature 
with color flow Doppler.
• Hepatic aspiration cytology—used to rule 
in HL (cats) or sample mass lesions; most 
clinicians avoid aspiration of obstructed 
biliary structures to avoid iatrogenic bile 
leakage and peritonitis.
• Ultrasound‐guided needle biopsy—
strongly contraindicated; may cause 
iatrogenic bile peritonitis.
• Laparotomy—best approach; allows tissue 
biopsy; biliary decompression; mass excision: 
cholelith or inspissated bile removal; cholecyst-  
ectomy or creation of biliary‐enteric 
anastomosis; CBD stent insertion.
• Laparoscopic procedures not prioritized  
because of need to completely evaluate 
biliary structures, ensure bile duct patency, 
and provide biliary decompressive surgeries.
• Gross—distended, tortuous bile duct, 
distended GB: cause often grossly apparent; 
obstruction >2 weeks: large, dark green to 
dark mahogany‐colored liver; chronic 
complete obstruction often associates with 
white or clear GB bile.
  TREATMENT
Inpatient—surgical intervention for EHBDO 
unless the cause is pancreatitis with prospect 
for resolution with supportive care.
• Fluid therapy—depends on underlying 
conditions; rehydrate and provide mainte-
nance fluids before general anesthesia and 
surgical interventions.
• Water‐soluble vitamins—in IV fluids; B 
complex (2 mL/L polyionic fluids).
• Initiate antibiotic therapy before surgery—
see Drug(s) of Choice.
• Vitamin K1—parenteral administration if 
EHBDO >5–7 days (see Drug(s) of Choice) 
before surgical interventions, abdominal or 
visceral aspiration cytology, placement of 
central lines or urinary catheters.
ACTIVITY
Depends on patient status and coagulopathy.
DIET
• Maintain nitrogen balance—avoid protein 
restriction.• Restrict fat if overt fat malassimilation 
caused by lack of enteric bile acids in chronic 
EHBDO—rare.
• Supplement fat‐soluble vitamins—vitamins 
E and K most urgent; supplements of vitamins 
D and A can lead to toxicity, thus careful use 
only in chronic unresolvable EHBDO.
• Water‐soluble vitamin E—necessary in 
chronic EHBDO (see Drug(s) of Choice).
• Vitamin K—parenteral only, use SC or IM 
routes only.
• Inform client that surgical biliary decom-
pression essential (unless resolvable pancreati-
tis or cholelith obstruction).
• Warn client that surgical success contingent 
on underlying cause, results of liver biopsy, 
infection, and individual variables.
• Surgical exploration—imperative for 
determining underlying cause and for 
implementing definitive treatment unless 
obvious pancreatitis with hope for resolution.
• Excise masses, remove choleliths and 
inspissated bile; ensure common duct patency.
• Resect GB—if necrotizing cholecystitis, 
GBM, or GB cholelithiasis.
• Biliary‐enteric anastomosis—if irresolvable 
occlusion of CBD: e.g., fibrosing pancreatitis, 
or neoplasia; anastomotic stoma at least 2.5 cm  
wide; chronic recurrent infection likely after 
biliary‐enteric anastomosis; warn clients that 
temporary stenting instead of biliary‐enteric 
anastomosis may be complicated by infection 
and stent obstruction, esp. in cats.
• Hypotension and bradycardia (vasovagal 
reflex)—may develop during biliary tree 
manipulation; ensure availability of emer-
gency drugs (anticholinergics) and ventilatory 
support for rescue endeavors.
• Cholangiovenous reflux—bacteria and 
endotoxins during surgery from biliary tree 
manipulations in septic conditions; contrib -
utes to perioperative hypotension; all 
suspected EHBDO patients should be given 
broad‐spectrum IV antimicrobials pre‐, intra‐, 
and postoperatively (during surgery after 
tissue and bile collection for bacterial culture).
• Ensure IV catheter access and volume 
expansion before surgery—use colloids only 
when plasma unavailable; be prepared for 
hemorrhage (have whole blood or packed red 
blood cells [RBCs] available).
• Surgical biopsies—submit tissue and 
particulate bile for aerobic and anaerobic 
bacterial culture; submit tissue for histology. 
Culture biliary debris; if GB removed, scrape 
wall to collect mucoid wall adherent material. 
Also collect GB wall, liquid bile, and liver 
tissue for culture. Combine all samples into a 
single culture for best bacterial recovery.
• Cytology—tissue and bile; cytology may 
detect bacterial infection and fluke eggs not recognized in biopsy sections; bile, biliary debris, 
and GB wall: more likely to harbor bacteria.
• Sclerosing or destructive feline cholangitis 
(intrahepatic ductopenia associated with 
lymphocytic or nonsuppurative or suppura -
tive CCHS) may clinically emulate EHBDO; 
does not respond to biliary tree decompres -
sion; liver biopsy necessary for definitive 
Vitamin K1
• Provide 12–36h before surgery—0.5–1.5 mg/
kg IM/SC, 3 doses at 12h intervals. Caution : 
avoid IV, may cause anaphylaxis.
• If chronic EHBDO not resolvable, 
parenteral vitamin K1 given chronically with 
frequency titrated using prothrombin time 
(PT); too much vitamin K1 causes hemolytic 
(Heinz body) anemia in cats.
• Oral vitamin K ineffectual owing to low 
bioavailability in EHBDO.
Vitamin E
• If chronic EHBDO nonresolvable, use 
water‐soluble vitamin E (d‐ α‐tocopheryl 
polyethylene glycol succinate [TPGS]‐vita-
min E)—10 U/kg/day PO.
• T reat early to allow response before invasive 
catheterizations, sampling, or surgical procedures.
Before surgery —broad‐spectrum antimicrobi-
als for potential biliary infection because 
surgical manipulations may disseminate 
bacteremia; initially use antibiotics with wide 
spectrum, e.g., triad of ticarcillin 25 mg/kg 
IV q8h, metronidazole 7.5 mg/kg IV/PO 
q12h, enrofloxacin 5 mg/kg PO q12–24h 
(24h dose in cats no greater than 5 mg/
kg/24h to avoid retinopathy).
Antioxidants
• Vitamin E ( α‐tocopherol acetate)—10– 
100 IU/kg; a larger than normal (normal = 
10 IU/kg/day) oral dose needed in chronic 
EHBDO if fat‐soluble vitamin used; lower 
dose used with water‐soluble vitamin E 
(preferred, see previous).
• S‐adenosylmethionine (SAMe)—20‐40 mg/ 
kg/day PO enteric‐coated tablet 1–2h before 
feeding; choleretic with high‐dose adminis -
tration via glutathione (GSH) provoked bile 
flow.
Ursodeoxycholic Acid
• 10–15 mg/kg PO per day— after biliary 
decompression  as a choleretic; ensure adequate 
hydration to achieve choleresis; inappropriate 
before  biliary decompression: can accelerate 
liver injury in EHBDO.(continued)  Bile Duct Obstruction (Extrahepatic)

176  Blackwell’s Five-Minute Veterinary Consult  
B
• Beneficial effects: antifibrotic, anti‐  
endotoxic, hepatoprotectant, anti‐apoptotic, 
immunomodulator.
Bowel Preparation before Surgery
• Mechanical cleansing of colon with water 
or crystalloid fluids—may reduce endotox-
emia potentiating perioperative hypotension.
• Acutely alter enteric flora to reduce enteric 
translocation of opportunistic pathogen with 
medications given either PO or by high 
enema instillation—neomycin 22 mg/kg q8h; 
lactulose 1–2 mL/kg q8h; metronidazole 
7.5 mg/kg q12h; enrofloxacin 2.5 mg/kg 
q12h PO; rifaximin 5–10 mg/kg q12h, at 
present limited experience with rifaximin in 
dogs and cats; probiotic bacteria, empirical 
product dose but has unproven efficacy.
Gastrointestinal Protectants
• Agents reducing gastric acidity—omepra-
zole or pantoprazole (pump inhibitors) or 
famotidine (H2 blocker) combined with 
sucralfate for local cytoprotection if PO 
medications tolerated and enteric bleeding 
recognized (stagger sucralfate administration 
from other oral medications to avoid drug 
interactions).
• Antiemetics—maropitant (Cerenia®) or 
ondansetron.
• Provide biliary decompression before 
institution of ursodeoxycholic acid.
• Take care to reduce drug dosages for 
medications eliminated in bile if EHBDO.
• Avoid invasive procedures—sampling, biopsy, 
surgical interventions before vitamin K1.
See Surgical Considerations.
  FOLLOW‐UP
• Depends on underlying condition.
• Total bilirubin values acutely reflect biliary 
decompression; values normalize within days.
• Liver enzyme activities—decline slowly.
• CBC—repeat q2–3 days initially if septic.
• Bile peritonitis—evaluate abdominal girth, 
body weight, and fluid accumulation.
• Determine necessity for pancreatic 
enzyme supplementation based on site of 
biliary‐enteric anastomosis; patients with 
cholecystojejunostomy may benefit from enzyme supplementation; cannot rely on 
trypsin‐like immunoreactive (TLI) 
substance to estimate pancreatic exocrine 
adequacy in this circumstance; sequentially 
evaluate body weight and condition, check 
feces for steatorrhea; only relevant if animal 
is fed a normal fat‐containing diet; if 
steatorrheic after biliary‐enteric anastomosis 
and patient is anicteric, reduce dietary fat 
intake and supplement pancreatic enzymes. 
Warning : pancreatic enzymes can induce 
oral or esophageal injury, especially in 
cats—must be mixed in food or adminis -
tered in capsule or tablet form, followed by 
liquid or food to prevent mucosal adherence 
and injury.
• Bile peritonitis.
• Restenosis of bile duct—if not bypassed 
and only stented to achieve biliary 
decompression.
• Stenosis of biliary‐enteric anastomosis.
• Severe enteric hemorrhage with EHBDO—
hypertensive enteric vasculopathy with 
coagulopathy (vitamin K deficiency).
• Hemorrhage during surgery.
• Septic bacteremia or systemic inflamma -
tory response syndrome (SIRS) during or 
after surgery.
• Perioperative unresponsive hypotension—
persistent vasovagal reflex or sepsis related.
• Vasovagal reflex.
• Cholangiovenous reflux.
• Depends on underlying disease.
• Prognosis good if fibrosing pancreatitis and 
pancreatic inflammation resolve; bile duct 
patency may return without surgery.
• Beware : biliary tree distention often persists 
(ultrasound imaging) after EHBDO resolution.
• Permanent peribiliary fibrosis from 
EHBDO.
• Cats with sclerosing cholangitis or 
ductopenia mimic EHBDO but show no 
response to biliary decompression; liver 
biopsy is essential for diagnosis.
Considerations/Precautions
• Anticipate bleeding tendencies, vasovagal 
reflex, and cholangiovenous reflux during 
surgical procedures.
• Always submit liver and biliary tree biopsies 
for histology; all tissues, crushed choleliths, 
and biliary debris for bacterial culture (aerobic, 
anaerobic).  MISCELLANEOUS
• See Causes.
• Sclerosing or destructive lymphocytic 
cholangitis (cats) and destructive suppurative 
cholangitis causing ductopenia and idiopathic 
or toxic ductopenia are confused with EHBDO.
SEE ALSO
• Gallbladder Mucocele.
• CBD = common bile duct.
• CCHS = cholangitis/cholangiohepatitis 
syndrome.
• DIC = disseminated intravascular coagulation.
• DPM = ductal plate malformation.
• EHBDO = extrahepatic bile duct 
• GB = gallbladder.
• GBM = gallbladder mucocele.
• GSH = glutathione.
• HL = hepatic lipidosis.
• SAMe = S‐adenosylmethionine.
• SIRS = systemic inflammatory response 
syndrome.
• TLI = trypsin‐like immunoreactive.
• TPGS‐Vitamin E = d‐ α‐tocopheryl 
polyethylene glycol succinate.
Center SA. Diseases of the gallbladder and 
biliary tree. Vet Clin North Am Small Anim 
Pract 2009, 39(3):543–598.
Mehler SJ, Mayhew PD, Drobatz KJ, et al. 
Variables associated with outcome in dogs 
undergoing extrahepatic biliary surgery: 60 cases 
(1988–2002). Vet Surg 2004, 33:644–649.
Consulting Editor  Kate Holan
available onlineBile Duct Obstruction (Extrahepatic)  (continued)

Canine and Feline, Seventh Edition  177
BBile Peritonitis
  BASICS
OVERVIEW
• Chemical peritonitis due to release of free 
bile into the abdominal cavity.
• Can involve focal or diffuse peritoneal 
inflammation, depending on chronicity and 
causal factors, and omental adhesions.
• More common in dog than in cat.
• No age, breed, or sex predilection.
SIGNS
• Acute presentation if septic peritonitis.
• May have chronic illness if nonseptic.
• Rare asymptomatic biliary rupture associated 
with omental encapsulation of leakage.
• Abdominal discomfort—vague.
• Gastrointestinal signs—anorexia, vomiting, 
diarrhea.
• ± Abdominal distention.
• Variable jaundice.
• Collapse, if septic.
• Variable (cranial) abdominal pain.
• Jaundice.
• ± Fever.
• ± Endotoxic shock, if septic.
• Limited arterial perfusion (cystic artery) to 
gallbladder (GB) fundus predisposes to 
ischemic necrosis and GB rupture.
• T rauma to biliary structures—automobile 
injuries, surgical, animal bites, gunshot wounds, 
cystic artery laceration during cholecystocentesis.
• Common bile duct (CBD)—frequent site 
of rupture with blunt trauma.
• Cholecystitis/choledochitis—may derive 
from GB mucocele (GBM); sepsis more 
common with necrotizing cholecystitis.
• Extrahepatic bile duct obstruction 
(EHBDO)—may derive from neoplasia, 
cholelithiasis, pancreatitis, duct stricture.
• Focal, small-volume, bile peritonitis—
associated with cholecystitis; may reflect 
omental entrapment of bile or transmural 
bile leakage without rupture.
• Chemical peritonitis due to bile—predisposes 
to septic peritonitis.
  DIAGNOSIS
• Conditions promoting inflammation/
devitalization of biliary structures—e.g., cholecystitis, choledochitis, neoplasia, GBM, 
neoplasia, blunt trauma.
• Conditions causing EHBDO—e.g., 
neoplasia, choleliths, pancreatitis, duct 
stricture/fibrosis.
• Sepsis or endotoxemia.
• Ascites—in jaundiced cirrhotic patient.
• Nonhepatic conditions causing abdominal 
effusion and jaundice.
CBC
Inflammatory leukogram—left shift and toxic 
neutrophils if necrotizing cholecystitis or 
sepsis; nonregenerative anemia if chronic 
• High liver enzymes, especially alkaline 
phosphatase (ALP); hyperbilirubinemia; ± 
hypoalbuminemia; ± prerenal azotemia.
• Electrolyte, fluid, and acid-base distur-
bances; hyponatremia common.
Bilirubinuria
Coagulation tests—abnormal if sepsis 
syndrome, disseminated intravascular 
coagulation (DIC), or chronic EHBDO.
IMAGING
• Abdominal radiography—reduced 
abdominal detail, generalized or focal in GB 
area; cranial abdominal mass effect; rare 
mineralized cholelith or biliary gas 
(emphysematous cholecystitis).
• Thoracic radiography—rare bicavity 
effusion (pleural effusion), signs of trauma 
(e.g., fractured rib, hernia).
• Abdominal ultrasonography—effusion; 
EHBDO—distended GB or CBD; cholecysti -
tis/choledochitis— thick GB or duct wall; 
necrotizing cholecystitis—segmental GB wall 
hyperechogenicity, laminated wall (represents 
necrosis); pericholecystic fluid; hepatic/
pancreatic mass effect: common with bile 
peritonitis; choleliths or GBM (“kiwifruit 
sign”); gas in GB or bile ducts (emphysematous 
inflammation, implicates gas-forming 
organisms) casting acoustic shadow; ruptured 
GB may be difficult to image; liver size usually 
normal; variable parenchymal echogenicity 
reflects hepatic pathology (e.g., ascending 
cholangitis/cholangiohepatitis [CCHS]).
• Abdominocentesis—physicochemical, 
cytologic, and culture evaluations; ultrasound 
guidance optimizes sampling; sample close to 
biliary structures but avoid structure 
• Cytology—impression smears of GB, liver, 
and bile (with particulate material) used for 
immediate detection of infection and 
neoplasia; modified transudate or exudate, 
phagocytized/free bile, and bilirubin.• Acellular mucinous material reflects biliary 
mucin production; GBM material may be 
free within abdominal cavity.
• Ratio of bilirubin in effusion : serum 
usually ≥2–3 : 1.
• Bacterial aerobic/anaerobic culture and 
sensitivity—effusion, GB wall, liver, GB 
contents; Gram-negative enteric opportunists 
and anaerobes most common; polymicrobial 
infection possible.
• Exploratory laparotomy—appropriate for 
definitive diagnosis and treatment; permits 
cholecystectomy, cholecysto-enterostomy, 
duct or GB repair.
• Liver biopsy—important, evaluates for 
antecedent or coexistent disease, sample 
distant to the GB to avoid artifacts.
Depend on cause and site of rupture.
  TREATMENT
• Inpatient—expediency of surgery depends 
on patient condition: achieve euhydration, 
correct electrolyte and acid-base status, 
provide preoperative antimicrobial treatment 
for best survival.
• Abdominal lavage to reduce peritoneal 
contamination if surgery delayed; use warm 
polyionic fluids and aseptic technique.
• Surgical experience important for best 
outcome—complicated resections and 
anastomoses may be required.
• Need for cholecystectomy decided at 
surgery; discolored GB wall indicates 
ischemic devitalized wall.
• Antimicrobials—in all patients, initiate 
broad-spectrum antimicrobials before  
surgical intervention; enteric Gram-
negative and anaerobic organisms most 
common opportunists (good initial choices: 
ticarcillin, piperacillin, or third-generation 
cephalo  sporins, with enro-floxacin and 
metronidazole); customized antimicrobial 
treatment, thereafter based on cultures; 
continue antimicrobials ≥4–8 weeks if signs 
of infection confirmed by culture or on 
cytology.
• Vitamin K1 (0.5–1.5 mg/kg IM/SC q12h 
for up to 3 doses)—all jaundiced patients 
before  surgery.
• Prepare for blood component ± synthetic 
colloid therapy.
• Antiemetics if patient is vomiting— 
 metoclopramide (0.2–0.5 mg/kg PO/SC 
q6–8h or 1–2 mg/kg/24h IV by CRI); 
ondansetron (0.5–1.0 mg/kg q12h IV/PO

178  Blackwell’s Five-Minute Veterinary Consult  
B
30 min before feeding); maropitant (1.0 mg/kg/
day IV/SC/PO max 5 days).
• Proton pump inhibitor if gastric bleeding—
pantoprazole (0.7–1.0 mg/kg IV q12–24h); 
omeprazole (0.5–1.0 mg/kg PO q12–24h); 
H2-receptor antagonists if proton pump 
inhibitor is not available: famotidine 
(0.5–2.0 mg/kg PO/IV/SC q12–24h); 
sucralfate (0.25–1.0 g PO q8–12h).
• Ursodeoxycholic acid as choleretic and 
hepatoprotectant if GBM, choleliths, CCHS, 
or chronic hepatitis—may administer 
chronically if GBM or cholelithiasis: 
10–15 mg/kg PO daily, divided, with food 
for best bioavailability.
• Antioxidants—vitamin E (10 IU/kg/24h); 
S-adenosylmethionine (SAMe, with proven 
bioavailability and efficacy) 20 mg/kg PO 
daily 2h before feeding until enzymes 
normalize, indefinitely if chronic hepatitis or 
CCHS, GBM, inspissated bile syndrome; 
choleretic influence requires higher dose 
(40 mg/kg/day).
  FOLLOW-UP
• Sequential hematologic, biochemical, and 
imaging tests.• Repeat abdominocentesis to assess continued 
infection and/or bile leakage as indicated.
• Cholangitis/cholangiohepatitis.
• Recurrent bacterial cholangitis if biliary-
enteric anastomosis required.
• High survival rate for dogs with sterile bile 
peritonitis, if successful surgery, depending on 
• Higher mortality in septic bile peritonitis 
(up to 73%).
• Anticipate slow clinical recovery and 
normalization of liver enzymes, but rapid 
resolution of hyperbilirubinemia with 
successful surgery.
SEE ALSO
• ALP = alkaline phosphatase.• CBD = common bile duct.
• CCHS = cholangitis/cholangiohepatitis.
• GBM = GB mucocele.
Mayhew PD, Holt DE, McLear RC, et al. 
Pathogenesis and outcome of extrahepatic 
biliary obstruction in cats. J Small Anim 
Pract 2002, 43:247–253.
Mehler SJ. Complications of the extrahepatic 
biliary surgery in companion animals. Vet 
Clin North Am Small Anim Pract 2011, 
41:949–967.
undergoing extrahepatic biliary surgery: 60 
cases (1988–2002). Vet Surg 2004, 
33:644–649.
Consulting Editor  Kate HolanBile Peritonitis  (continued)

Canine and Feline, Seventh Edition  179
B
  BASICS
OVERVIEW
• Bilious vomiting syndrome (BVS) is 
suspected to be secondary to alterations in 
normal gastrointestinal (GI) motility. BVS is 
associated with chronic intermittent vomiting 
of bile, thought to be the result of reflux of 
intestinal contents (bile) into the stomach. The 
normal aboral gastric and intestinal motility 
and functional pylorus prevent the reflux of bile 
back into the stomach. When bile is refluxed 
into the stomach it is normally rapidly removed 
by subsequent peristaltic contractions. Bile 
remaining in the gastric lumen along with 
gastric acid and pepsin can subsequently cause 
gastric mucosal damage. • Clinical signs often 
occur early in the morning, suggesting that 
prolonged fasting or gastric inactivity may 
modify normal motility patterns, resulting in 
bile reflux. • System affected—GI.
• Commonly observed in dogs, rarely in cats. 
• Most animals are young or middle‐aged. 
• No breed or sex predisposition.
SIGNS
• Chronic intermittent vomiting of bile 
associated with empty stomach. Signs 
generally occur late at night or early in 
morning. Signs may occur daily, but usually 
intermittent. Between episodes, animal 
appears normal and most dogs appear healthy 
immediately after vomiting episodes. • Results 
of physical examination usually unremarkable.
• Cause unknown (idiopathic). • Primary 
gastric hypomotility or abnormal intestinal 
peristaltic motility are suspected as probable 
underlying causes. • Conditions causing 
gastritis, duodenitis, or intestinal obstructive 
disease may be responsible for altered proximal 
GI motility and can cause bile reflux; investi  - 
gate for parasitism (e.g., Giardia ), inflamma -
tory bowel disease (IBD), intestinal neoplasia, 
or obstructions as possible etiologies. 
• Previous pyloric opening or resection surgery 
can increase risk of enterogastric reflux.
  DIAGNOSIS
• Any number of GI and non‐GI disorders 
can cause chronic vomiting. Giardia  should 
be excluded since signs of this disease may 
mimic those of BVS. • IBD can result in bile 
reflux. • Intestinal obstruction or partial 
obstructions should be ruled out.
Results usually unremarkable.OTHER LABORATORY TESTS
• Fecal examination to detect Giardia  or 
other parasites. • Baseline cortisol to rule out 
hypoadrenocorticism. • GI panel—pancreatic 
lipase immunoreactivity (PLI), trypsin‐like‐
immunoreactivity (TLI), cobalamin, folate.
IMAGING
• Barium contrast study may reveal delayed 
gastric emptying, although finding must be 
interpreted with caution. • Barium given 
with meals, radiopaque markers, or using 
special motility capsule (Smartpill®) may also 
demonstrate delayed gastric motility.
• Endoscopic findings frequently unremarkable 
and help rule out underlying GI disease. • May 
be evidence of bile in stomach or gastritis in 
antral region of stomach. • Endoscopy useful 
to rule out structural or inflammatory disease, 
since BVS is diagnosis of exclusion.
  TREATMENT
• Generally not serious debilitating disorder 
if truly BVS, but important to rule out major 
conditions such as gastritis, IBD, or GI 
neoplasia. • Idiopathic bilious vomiting cases 
generally treated symptomatically on an 
outpatient basis and treatment response 
supports suspected diagnosis. • Feeding the 
animal small frequent meals, including late 
evening meal, often resolves clinical signs; 
food possibly could act as buffer to refluxed 
bile or may in some way enhance GI motility. 
• T rial with hypoallergenic diet (novel protein 
or hydrolyzed protein) can also improve 
clinical signs, which may actually suggest 
underlying food‐responsive enteropathy. • If 
diet modification fails, medical treatment 
should be considered.
• Choices include agents for gastric mucosal 
protection against refluxed bile or use of 
gastric prokinetic agents to improve motility. 
• Often single evening dose of medication 
may be all that is required to prevent clinical 
signs if signs occur at night. • Drugs for 
gastric mucosal protection include various 
antacids or sucralfate (1 g/25 kg q8h). 
• Drugs that block gastric acid production, 
including famotidine (0.5–1.0 mg/kg 
q12h–24h), ranitidine (1–2 mg/kg q8–12h), 
and omeprazole (0.7–1.5 mg/kg q12–24h) 
may be beneficial; ranitidine has mild gastric 
prokinetic effects in vitro and may be 
beneficial, but is less effective acid reducer. 
• Specific gastric prokinetic agents include metoclopramide (0.2–0.4 mg/kg PO q6–8h) 
and cisapride (0.5 mg/kg PO q8–12h); 
cisapride only available through compound-
ing pharmacies. • Erythromycin (0.5–1 mg/
kg q8h) stimulates gastric motility by 
activation of motilin receptors and may also 
resolve signs.
• Gastric prokinetic agents should not be 
administered in patients with GI obstruction. 
• Metoclopramide can cause nervousness, 
anxiety, or depression. • Cisapride at higher 
doses can cause vomiting, diarrhea, or 
abdominal cramping. • Erythromycin can 
cause vomiting.
  FOLLOW‐UP
• Most patients respond to one of these 
treatments and clinical response supports the 
diagnosis. • Failure to respond suggests 
another underlying or causative factor.
Gastroesophageal reflux.
SEE ALSO
• Gastric Motility Disorders.
• Gastroesophageal Reflux.
• BVS = bilious vomiting syndrome.
• IBD = inflammatory bowel disease.
• PLI = pancreatic lipase immunoreactivity. 
• TLI = trypsin‐like‐immunoreactivity.
Ferguson LE, Wennogle SA, Webb CB. 
Bilious vomiting in dogs: retrospective 
study of 20 cases (2002–2012). J Am Anim 
Hosp Assoc 2016, 52:157–161.
Washabau RJ. Gastrointestinal motility 
disorders and gastrointestinal prokinetic 
therapy. Vet Clin North Am Small Anim 
Pract 2003, 33(5):1007–1028.
Webb C, T wedt DC. Canine gastritis. Vet 
Clin North Am Small Anim Pract 2003, 
33(5):969–985.
Author  Leah Ferguson
of David C. T wedt.Bilious Vomiting Syndrome

B180  Blackwell’s Five-Minute Veterinary Consult  
BBlastomycosis
  BASICS
A systemic, mycotic infection caused by the 
dimorphic soil organism Blastomyces dermatitidis .
• A small spore (conidia) shed from the 
mycelial phase ( Ajellomyces dermatitidis ) of 
the organism growing in soil is inhaled, 
entering the terminal airway.
• At body temperature, spore transforms to its 
yeast form, which may initiate infection in lungs.
• From a focus of mycotic pneumonia, yeast 
may disseminate hematogenously throughout 
the body.
• Immune response produces pyogranulo­
matous inflammation.
• Respiratory—85% of affected dogs.
• Eyes, skin, subcutaneous tissues, lymphatic, 
and musculoskeletal—commonly affected.
• Reproductive, nasal cavity, and heart—less 
commonly affected.
• Subclinical infection is uncommon.
Depends on environmental and soil 
conditions that favor growth of Blastomyces . 
Growth of organism requires sandy, acidic soil 
and proximity to water.
Most common along the Mississippi, Ohio, 
and Tennessee river basins. Also reported in 
Great Lakes and St. Lawrence River areas, 
southern Canada, mid ­Atlantic states; has 
been found outside endemic area in Colorado.
Species
• Predominantly dog.
• Occasionally cat.
Large ­breed dogs weighing ≥25 kg, especially 
sporting breeds; may reflect increased 
exposure rather than susceptibility.
• Dogs—most common in those 1–5 years of 
age; uncommon after 7 years of age.
• Cats—no age predilection noted.
• Dogs—males in most studies.
• Cats—none noted.
SIGNS
• Weight loss, hyporexia.
• Cough, dyspnea.
• Ocular inflammation/discharge.
• Draining skin lesions.
• Lymphadenitis.
• Lameness.• Seizures or neurologic deficits with CNS 
• Syncope if cardiac involvement.
Dogs
• Fever up to 104 °F (40 °C) in ~50% of 
patients.
• Harsh, dry lung sounds, increased 
respiratory effort.
• Generalized or regional lymphadenopathy 
with or without skin lesions or subcutaneous 
swellings.
• Uveitis with or without secondary 
glaucoma and conjunctivitis, ocular exudates, 
and corneal edema.
• Lameness—bone involvement in up to 30%.
• Testicular enlargement and prostatomegaly—  
occasional.
• Murmur and atrioventricular (AV) 
block—with endocarditis and myocarditis.
Cats
• Increased respiratory effort.
• Granulomatous skin lesions.
• Visual impairment.
• Wet environment—banks of rivers, streams, 
lakes or swamps; most affected dogs live 
within 400 meters of water.
• Exposure to recently excavated areas.
• Reported in indoor ­only cats.
  DIAGNOSIS
• Respiratory signs—bacterial pneumonia, 
metastatic neoplasia, heart failure, pleural 
effusion, or other fungal infection.
• Lymphadenopathy—similar to 
lymphoma.
• Combination of respiratory disease with 
ocular, bony, or skin/subcutaneous involve­
ment in a young dog supports the diagnosis.
• CBC reflects inflammation; mild anemia in 
chronic cases.
• High serum globulins, borderline hypoal­
buminemia with chronic infection.
• Hypercalcemia (generally mild) in some dogs.
• Blastomyces  yeasts may be found in urine of 
dogs with prostatic involvement; mild 
proteinuria can be present.
• Urine or serum antigen testing—sensitivity 
>90%; sensitivity greater with urine test; 
cross­reacts with other fungal infections (e.g., 
histoplasmosis).
• Agar gel immunodiffusion (AGID)—not 
sensitive early in disease, but very specific for 
infection.IMAGING
Radiographs
• Lungs—generalized interstitial to nodular 
infiltrate, may be nonuniform distribution.
• T racheobronchial lymphadenopathy.
• Changes may resemble metastatic neoplasia.
• Pleural effusion has been reported in dogs.
• Focal bone lesions—lytic and proliferative; 
can be mistaken for osteosarcoma.
• Cytology of lymph node aspirates, lung, or 
lytic bone aspirates, tracheal wash fluid, or 
impression smears of skin lesions—best 
method for diagnosis.
• Histopathology of bone biopsies or 
enucleated eyes.
• Organisms—usually plentiful in tissues; 
may be scarce in tracheal washes if there is no 
productive cough.
• Lesions—pyogranulomatous with budding 
5–20  μm diameter yeast; thick, refractile, 
double ­contoured cell wall; occasionally very 
fibrous with few organisms found.
• Special fungal stains—facilitate organism 
detection.
  TREATMENT
Severely dyspneic dogs—require prolonged 
oxygen support; about 25% of dogs have 
worsening of respiratory disease during first 
days of treatment, attributed to an inflamm­
atory response.
ACTIVITY
Patients with respiratory compromise must be 
restricted.
DIET
N/A
• T reatment is costly and long term.
• Infected dogs are not contagious to other 
animals or people.
• Removal of abscessed lung lobe may be 
required if medical treatment ineffective.
• Blind eyes should be enucleated to remove 
potential sites of residual infection.
Itraconazole
• Dogs—5 mg/kg PO q12h with a fat ­rich 
meal (e.g., canned dog food) for the first 3 
days, then reduce to 5 mg/kg PO q24h.

Canine and Feline, Seventh Edition  181
B
B
• Cats—5 mg/kg PO q12h; open the 100 mg 
capsules containing pellets and mix with 
palatable food.
• Avoid antacid drugs as absorption best in 
acidic environment.
• T reat for minimum 90 days, or for 1 month 
after all signs of disease have resolved (which  ­ 
ever is longer).
• Absorption of compounded itraconazole is 
unreliable and use is not recommended.
Fluconazole
• Dogs—5 mg/kg PO q12h.
• Cats—5–10 mg/kg PO q12–24h; 50 mg/cat.
• Inexpensive, but may require longer 
treatment duration.
Amphotericin B
• For dogs with neurologic signs or life ­
threatening disease.
• 0.5–1.0 mg/kg IV q48h; use lipid complex 
for dogs with renal dysfunction.
Corticosteroids—may allow continued 
proliferation of organisms; patients with 
previous steroid therapy require longer 
treatment duration; for dogs with life ­
threatening dyspnea, dexamethasone 
(0.1–0.2 mg/kg/day IV) for 2–3 days may be 
given with itraconazole treatment; taper and 
discontinue corticosteroids as soon as possible.
Itraconazole and Fluconazole Toxicity
• Anorexia—most common sign; attributed 
to liver toxicity; monitor serum alanine 
aminotransferase (ALT) activity monthly or 
when anorexia occurs; temporarily discontinue 
drug for patients with anorexia and moderate 
ALT activity elevation; after appetite improves, 
restart at half the previous dose.
• Ulcerative dermatitis—in some dogs due to 
vasculitis; dose related; temporarily 
discontinue drug until ulcers resolve, then 
Amphotericin B Toxicity
• Only absolute contraindication to therapy 
is anaphylaxis, but major limiting factor is 
cumulative nephrotoxicity.
• Monitor serum creatinine concentration 
throughout therapy—elevation above normal or 
20% greater than baseline considered significant.
  FOLLOW-UP
Serum chemistry—monthly to monitor for 
hepatic toxicity, or if anorexia develops.Thoracic Radiographs
• Considerable permanent pulmonary 
changes (fibrosis/scarring) may occur after the 
infection resolves, making determination of 
persistent active disease difficult.
• At 90 days of treatment—if active 
pulmonary disease, continue treatment for 
additional 30 days.
• If lungs appear normal, stop treatment and 
repeat radiographs again in 30 days.
• At 120 days of treatment—if the lungs 
appear the same as day 90, changes are 
residual (fibrosis); if clearer than day 90, 
continue treatment for 30 more days. If 
lesions are significantly worse than at 90 days, 
consider a change in therapeutic agent.
• Continue treatment as long as improvement is 
noted in the lungs; if there is no further 
improvement and no indication of active disease, 
the lesions are likely the result of scarring.
Urine Antigen Testing
• Positive test is generally related to active disease.
• If other signs have resolved, a negative test 
supports treatment discontinuation.
• Location of environmental growth of 
Blastomyces  organisms unknown, thus 
difficult to avoid exposure; exposure to lakes 
and streams may be restricted (but limited 
practicality).
• Dogs that recover from the infection may 
be immune to reinfection.
• Death—25% of dogs die during first week 
of treatment; early diagnosis improves chance 
of survival.
• Severe pulmonary disease and CNS 
involvement decrease prognosis.
• Recurrence—approximately 20% of dogs; 
usually within 3–6 months after completion 
of treatment; may occur >1 year after treat ­ 
ment; a second course of azole treatment 
cures most patients; drug resistance has not 
been observed.
• With early detection of blastomycosis, the 
prognosis in cats appears similar to dogs.
• Yeast form is not spread from animals to 
humans, except through bite wounds; 
inoculation of organisms from dog bites has 
occurred.
• Avoid cuts during necropsy of infected dogs 
and avoid needle sticks when aspirating lesions.• Warn clients that blastomycosis is acquired 
from an environmental source and that they 
may have been exposed to the source; the 
incidence in dogs is 10 times that in humans.
• Encourage clients with respiratory and skin 
lesions to inform their physicians that they 
may have been exposed to blastomycosis.
Azole drugs can have teratogenic effects 
(embryotoxicity found at high doses) and 
should ideally be avoided during pregnancy 
(but the risk of not treating the mother must 
be balanced with the theoretical risk of azole 
therapy to the fetuses).
Information on antigen testing: www.
miravistalabs.com
Crews LJ, Feeney DA, Jessen CR, et al. 
Radiographic findings in dogs with 
pulmonary blastomycosis: 125 cases 
(1989–2006). J Am Vet Med Assoc 2008, 
232:215–221.
Foy DS, T repanier LA, Kirsch EJ, et al. Serum 
and urine Blastomyces antigen 
concentrations as markers of clinical 
remission in dogs treated for systemic 
blastomycosis. J Vet Intern Med 2014, 
28:305–310.
Legendre AM, Rohrbach BW, Toal RL, et al. 
T reatment of blastomycosis with 
itraconazole in 112 dogs. J Vet Intern Med 
1996, 10:365–371.
Mazepa AS, T repanir LA, Foy DS. Retrospective 
comparison of the efficacy of fluconazole or 
itraconazole for the treatment of systemic 
blastomycosis in dogs. J Vet Intern Med 
2011, 25:440–445.
Spector D, Legendre AM, Wheat J, et al. 
Antigen and antibody testing for the 
diagnosis of blastomycosis in dogs. J Vet 
Intern Med 2008, 22:839–843.
Author  Daniel S. Foy
available online(continued)  Blastomycosis

B182  Blackwell’s Five-Minute Veterinary Consult  
BBlepharitis
  BASICS
Inflammation of outer (skin) and middle 
(muscle, connective tissue, and glands) 
portions of eyelid, usually with secondary 
inflammation of palpebral conjunctiva.
• Inflammation—immune mediated, 
infectious, endocrine mediated, self- and 
external trauma, parasitic, radiation, 
nutritional. Inflammatory response often 
exaggerated because conjunctiva is rich in 
mast cells and densely vascularized. 
• Meibomian gland dysfunction—bacterial 
lipases alter meibomian lipids and plug gland; 
produce irritating fatty acids, enhance 
bacterial growth, and destabilize tear film.
Ophthalmic
See Causes.
SIGNS
• Serous, mucoid, or mucopurulent ocular 
discharge. • Blepharospasm. • Eyelid 
hyperemia, edema, and thickening. 
• Pruritus. • Excoriation. • Depigmentation—  
skin, hair (in Siamese-type cats with color 
points, lightening of hair on affected lids due 
to increased skin temperature). • Alopecia. 
• Swollen, cream-colored meibomian glands. 
• Elevated, pinpoint meibomian gland 
orifices. • Abscesses. • Scales, crusts, papules, 
or pustules. • Single or multiple nodular 
hyperemic swellings. • Concurrent 
conjunctivitis and/or keratitis.
CAUSES
• Eyelid abnormalities—may promote 
self-trauma or moist dermatitis. • Prominent 
nasal folds, medial trichiasis, and lower lid 
entropion—shih tzu, Pekingese, English 
bulldog, Lhasa apso, pug; Persian and 
Himalayan cat. • Distichia—shih tzu, pug, 
golden retriever, Labrador retriever, poodle, 
English bulldog. • Ectopic cilia. • Lateral lid 
entropion—Chinese Shar-Pei, chow chow, 
Labrador retriever, Rottweiler. 
• Lagophthalmos—brachycephalic dogs; 
Persian, Himalayan, and Burmese cats. • Deep 
medial canthal pocket—dolichocephalic dogs. 
• Dermoids—Rottweiler, dachshund, and 
others; Burmese cat.
Allergic
• Type I (immediate)—atopy, food, insect 
bite, inhalant, Staphylococcus  hypersensitivity 
(SH). • Type II (cytotoxic)—pemphigus, 
pemphigoid, drug eruption • Type III 
(immune complex)—systemic lupus erythematosus (SLE), SH, drug eruption. 
• Type IV (cell mediated)—contact and flea 
bite hypersensitivity; drug eruption.
Bacterial
• Hordeolum—localized abscess of eyelid 
glands, usually staphylococcal; may be external 
(sty in young dogs, glands of Zeis) or internal 
(in old dogs, meibomian glands). • Generalized 
bacterial blepharitis and meibomianitis—usually 
Staphylococcus  or Streptococcus . • Bartonella 
henselae— chronic blepharoconjunctivitis in cats. 
• Pyogranulomas. • SH—young and old dogs.
• Sebaceous adenomas and 
adenocarcinomas—from meibomian gland. 
• Squamous cell carcinoma—white cats. 
• Mast cell—may appear as swollen, hyper  - 
emic lesion.
Other
• External trauma—eyelid lacerations, 
thermal or chemical burns. • Mycotic—
dermatophytosis; systemic fungal granulomas.
• Parasitic—demodicosis; sarcoptic mange; 
Cuterebra  and Notoedres cati. Note: Demodex 
injai has a propensity for sebaceous glands 
and can be associated with meibomian gland 
dysfunction in dogs, including chalazia and 
granulomatous blepharitis. • Chalazia—ster-
ile, yellow-white, painless meibomian gland 
swellings caused by granulomatous inflamma-
tory response to meibum in surrounding 
eyelid tissue. • Nutritional—zinc-responsive 
dermatosis (Siberian husky, Alaskan 
Malamute, puppies), fatty acid deficiency.
• Endocrine—hypothyroidism (dogs); 
hyperadrenocorticism (dogs); diabetic 
dermatosis. • Viral—chronic blepharitis in 
cats (feline herpesvirus type 1 [FHV-1]).
• Irritant—drug reaction (e.g., neomycin); 
smoke in environment; post-parotid duct 
transposition. • Familial canine dermato -
myositis—collie and Shetland sheepdog.
• Nodular granulomatous episclerokeratitis—
fibrous histiocytoma and collie granuloma; 
may affect eyelids, cornea, or conjunctiva.
• Eosinophilic granuloma—cats; may affect 
eyelids, cornea, or conjunctiva. • Eyelid contact 
with tear overflow and purulent exudate (tear 
burn). • Keratitis, conjunctivitis, dacryocysti-
tis. • Dry eye.
• Orbital disease. • Radiotherapy. • Idiopathic—  
especially Persians and Himalayans.
• Breed predisposition to eyelid abnormalities 
(e.g., entropion, ectropion). 
• Hypothyroidism—may promote chronic 
bacterial disease in dogs. • Canine seborrhea—  
may promote chronic generalized 
meibomianitis, with predisposition for 
Demodex injai  infection.  DIAGNOSIS
Clinical signs are diagnostic.
Usually normal unless metabolic cause (e.g., 
diabetic dermatosis).
Indicated for systemic disorders, including 
hypothyroidism.
• Eye examination—inciting cause, corneal 
ulcer, foreign body, distichia, ectopic cilia, 
keratoconjunctivitis sicca (KCS). • Ancillary 
ocular tests— fluorescein, Schirmer tear test.
• Thorough history and dermatologic exam: 
◦ Cytology—deep skin scrape, conjunctival 
scrape, or exudate from glands and pustules. 
◦ Wood’s light evaluation, dermatophyte 
culture. ◦ KOH preparation. ◦ Intradermal 
skin testing, other testing for hypersensitivity-
induced disease. ◦ Consider referral to a 
dermatologist for refractory cases. • Aerobic 
bacterial culture and sensitivity—of exudate 
from skin, conjunctiva, expressed meibomian 
glands, or pustules; often will not recover 
Staphylococcus  from patients with chronic 
meibomianitis and suspected SH. • Immuno -
fluorescent antibody assay or PCR for FHV-1 
and Chlamydia —in conjunctival scrapings from 
cats with primary conjunctivitis or keratitis. 
• Full-thickness wedge biopsy of eyelid.
Routine histopathology often nondiagnostic 
in chronic disease.
  TREATMENT
See Nursing Care.
• Prevent self-trauma—Elizabethan collar. 
• Cleanse eyelids—to remove crusts; warm 
compresses applied for 5–15 minutes 3–4 
times daily, avoiding ocular surfaces. Use 
saline, lactated Ringer’s solution, or a 
commercial ocular cleansing agent (e.g., I-Lid 
’n Lash®); clip periocular hair short. 
• Common underlying cause in cats is 
FHV-1 infection; minimize stress.
DIET
Only if food allergy.
In cats with FHV-1-related blepharitis, 
inform client that there is no cure and that 
clinical signs often recur when animal is 
stressed.

Canine and Feline, Seventh Edition  183
B
B
• Temporary everting eyelid sutures—spastic 
entropion; or in puppies before permanent 
surgical correction. • Repair eyelid lacerations. 
• Lancing—large abscesses only; lance and 
curette hordeola that resist medical treatment 
and chalazia that have hardened and cause 
keratitis; manually express infected 
meibomian secretions.
• Systemic—for bacterial eyelid infections 
(e.g., cephalexin 20 mg/kg IV q8h). For 
Bartonella henselae  infection in cats, therapy 
may include doxycycline (10 mg/kg PO q12h 
for 3 weeks), pradofloxacin (5–10 mg/kg PO 
q12–24h for 28–42 days), or azithromycin 
(10 mg/kg PO q24h for 3 weeks). • Topical—  
neomycin, polymyxin B, and bacitracin 
combination or chloramphenicol.
• Topical antibiotic ointment—q6–12h to 
prevent frictional rubbing of eyelid hairs or 
cilia on ocular surface. • Regularly flush 
debris from deep medial canthal pocket using 
saline, lactated Ringer’s solution, or ocular 
irrigant.
External Trauma
• Topical antibiotic ointment—q6–12h; in 
patients with spastic entropion and blepharo -
spasm until surgical correction. • Systemic 
antibiotics.
Allergic
• SH blepharitis—systemic broad-spectrum 
antibiotics and systemic corticosteroids 
(prednisolone 0.5 mg/kg PO q12h for 3–5 
days, then taper); many patients respond to 
systemic corticosteroids alone; systemic 
cyclosporine (5 mg/kg PO q24h until 
remission, then q48–72h) if refractory to 
corticosteroids; failure of treatment—consider 
injections of Staphylococcus aureus  bacterin 
(Staphage Lysate®). • Infected meibomian 
glands—oral tetracycline (15–20 mg/kg PO 
q8h), doxycycline (3–5 mg/kg PO q12h), or 
cephalexin (22 mg/kg PO q8h) for 3 weeks 
(the former two are lipophilic and cause 
decreased production of bacterial lipases and 
irritating fatty acids); topical polymyxin B 
and neomycin with 0.1% dexamethasone 
(q6–8h) or topical 0.02% tacrolimus 
compounded ointment (q8–12h). Some affected dogs might also require treatment for 
demodecosis . • Eyelid lesions associated with 
puppy strangles—treat generalized condition. 
• Atopy—see Atopic Dermatitis.
Bacterial
• Based on culture and sensitivity or serologic 
testing. • Pending results—topical polymyxin 
B and neomycin with 0.1% dexamethasone 
ointment (q4–6h) and systemic broad-
spectrum antibiotic.
Mycotic
Microsporium canis  infection—see 
Dermatophytosis.
Parasitic
Demodicosis, Notoedres  infection, sarcoptic 
mange—see relevant chapters.
Idiopathic
Clinical signs often controlled with topical 
polymyxin B and neomycin with 0.1% 
dexamethasone (q8–24h or as needed); 
occasionally may need prednisolone (0.5 mg/
kg PO q12h for 3–5 days, then taper) and/or 
systemic antibiotic.
• Topical corticosteroids—do not use with 
corneal ulceration. • Many cats with 
presumed idiopathic blepharoconjunctivitis 
have FHV-1 infection; topical and systemic 
corticosteroids may exacerbate infection. 
• Oral tetracycline and doxycycline—do not 
use in puppies and kittens. • Neomycin—
avoid topical use if possible cause of 
blepharitis. • Neomycin, bacitracin, and 
polymyxin—avoid topical ophthalmic use in 
cats due to rare but potentially fatal anaphy -
lactic reaction.
• Ectoparasitism—wear gloves; do not 
contact ocular surfaces with a drug topically 
applied to skin; apply artificial tear ointment 
to eyes for protection. • Topical gentamicin, 
neomycin, terramycin, and most ointments—
may cause irritant blepharoconjunctivitis 
(rare); withdrawal may resolve condition.
Staphylococcal bacterin may cause anaphy -
lactic reaction (rare).
  FOLLOW-UP
• Depends on cause, therapy. • Bacterial—
systemic and topical treatment for at least 3 weeks; should notice improvement within 10 
days. • Most common causes of treatment 
failure—use of subinhibitory antibiotic 
dosages, failure to correct one or more 
predisposing factors, early discontinuation of 
Depends on cause.
• Cicatricial lid contracture—results in 
trichiasis, ectropion, or lagophthalmos. 
• Spastic entropion—because of blepharo -
spasm and pain. • Qualitative tear film 
deficiency—loss of proper meibum secretion. 
• Recurrence of bacterial infection or FHV-1 
blepharoconjunctivitis.
Depend on cause.
• Sarcoptic mange.
SEE ALSO
• Atopic Dermatitis.
• Conjunctivitis—Cats.
• Conjunctivitis—Dogs.
• Epiphora.
• Keratitis—Nonulcerative.
• Keratitis—Ulcerative.
• Red Eye.
• KCS = keratoconjunctivitis sicca.
• SH = Staphylococcus  hypersensitivity.
Bettany S, Mueller R, Maggs D. Diseases of 
the eyelids. In: Maggs DJ, Miller PE, Ofri 
R, eds., Slatter’s Fundamentals of Veterinary 
Ophthalmology, 6th ed. St. Louis, MO: 
Saunders, 2018, pp. 127–157.
Author  Terri L. McCalla
available online(continued)  Blepharitis

B184  Blackwell’s Five-Minute Veterinary Consult  
B
  BASICS
Loss of vision in one or both eyes without 
ocular vascular injection or other externally 
apparent signs of ocular inflammation.
Results from abnormalities in focusing images 
on the retina, the retina detecting an image, 
optic nerve transmission, or the brain not 
interpreting images correctly.
• Nervous. • Ophthalmic.
• Dog and cat. • Any age, breed, or sex.
• Many causes (e.g., cataracts and progressive 
retinal atrophy) have a genetic basis and are 
often highly breed and age specific.
• Sudden acquired retinal degeneration 
syndrome (SARDS)—tends to occur in 
older dogs. • Optic nerve hypoplasia—  
congenital.
SIGNS
• Vary with underlying cause. • Bumping 
into objects. • Clumsy behavior. • Reluctance 
to move. • Impaired vision in dim light.
• Vary with underlying cause. • Decreased or 
absent menace or dazzle response. • Impaired 
visual placing responses.
CAUSES
• Cataracts—entire lens must become opaque 
to produce complete blindness; incomplete 
opacification may reduce performance of 
visually demanding tasks. • Loss of focusing 
power of the lens—rarely completely blinding; 
substantial hyperopia (far-sightedness) occurs 
when the optical power of the lens is not 
replaced after lens extraction or if the lens 
luxates posteriorly out of the pupillary plane 
and into the vitreous. • Retina—SARDS, 
progressive retinal atrophy (PRA), retinal 
detachment, taurine deficiency (cats), 
enrofloxacin toxicity (cats), ivermectin 
toxicity (dogs, cats). • Optic nerve—optic 
neuritis, neoplasia of the optic nerve or 
adjacent tissues, trauma, optic nerve hypoplasia, 
lead toxicity, excessive traction on the optic 
nerve during enucleation resulting in trauma 
to the contralateral optic nerve or optic 
chiasm (especially cats and brachycephalic 
dogs). • CNS (amaurosis)—lesions of the 
optic chiasm or tract, optic radiation, or 
visual cortex. CNS-associated vision loss that 
occurs at a level higher than the optic chiasm 
often has vague visual disturbances in which 
the patient has some vision, but clearly does 
not have normal vision.RISK FACTORS
• Poorly regulated diabetes mellitus—cataracts.
• Related animals with genetic cataracts or PRA.
• Systemic hypertension—retinal detachment.
• CNS hypoxia—blindness may become 
apparent after excessively deep anesthesia or 
revival from cardiac arrest.
  DIAGNOSIS
Signs
• Anterior segment inflammation and 
glaucoma—conjunctiva typically injected.
• Young patients—may lack menace responses, 
but will successfully navigate a maze or visually 
track hand movements or cotton balls. 
• Postictal period—transient vision loss. 
• Abnormal mentation—may be difficult to 
determine whether an animal is visual; other 
neurologic abnormalities help localize the lesion.
Causes
• Optic neuritis, retinal detachment, SARDS, 
or visual cortex hypoxia—sudden vision loss 
(over hours to weeks). • SARDS—often 
preceded by polyuria, polydipsia, polyphagia, 
and weight gain. • PRA—gradual vision loss, 
especially in dim light; apparently acute 
vision loss with sudden change in environ -
ment. • Cataract—either gradual or rapidly 
increasing opacification and vision loss in a 
quiet eye. • Optic nerve hypoplasia— 
congenital; may be unilateral or bilateral. 
• Optic neuropathy or CNS disease—other 
signs of neurologic abnormalities. • Pupillary 
light responses—usually normal with 
cataracts or visual cortex lesions; sluggish to 
absent with retinal or optic nerve diseases.
• Ophthalmoscopy—normal with early 
SARDS, retrobulbar optic neuritis, and higher 
visual pathway lesions; abnormal with retinal 
detachment and disorders of optic nerve head.
• Usually normal, unless underlying systemic 
disease. • Hyperglycemia or glucosuria—may 
note with diabetic cataracts. • Elevated alkaline 
phosphatase (ALP) enzyme activity and 
changes consistent with hyperadrenocorticism 
(Cushing’s syndrome)—suggest SARDS. 
• Retinal detachment secondary to systemic 
hypertension (cats)—azotemia or changes 
consistent with hyperthyroidism.
• Blood lead and serology for deep fungal or 
viral infections—consider for suspected 
optic neuritis (see Optic Neuritis and 
Papilledema).
• Low-dose dexamethasone suppression 
test—may help rule out Cushing’s syndrome 
with SARDS. • Sex hormone abnormalities 
are common in patients with SARDS.IMAGING
• Ocular ultrasound—may demonstrate 
retinal detachment (especially if the ocular 
media are opaque) or optic nerve mass lesion.
• Plain skull radiographs—seldom inform -
ative. • CT or MRI—often helpful with 
orbital or CNS lesions.
See Figure 1.
• Ophthalmic examination with a penlight—
usually permits diagnosis of cataracts or retinal 
detachments severe enough to cause blindness. 
• Ophthalmoscopy—may show PRA, late 
SARDS, or optic nerve disease; normal exam 
suggests early SARDS, retrobulbar optic 
neuritis, or a CNS lesion. • Systemic arterial 
blood pressure—determine in patients with 
retinal detachment. • Electroretinography—
differentiates retinal from optic nerve or CNS 
disease. • Cerebrospinal fluid (CSF) tap—
may be of value with a neurogenic cause of 
vision loss.
  TREATMENT
• T ry to obtain a definitive diagnosis on an 
outpatient basis before initiating treatment.
• Consider referral before attempting 
empirical therapy. • Most causes are not 
fatal, but must perform a workup to rule out 
potentially fatal diseases. • Reassure client 
that most causes of a blind quiet eye are not 
painful and that blind animals can lead 
relatively normal and functional lives. 
• Warn client that the environment should 
be examined for potential hazards to a blind 
animal. • Advise client that patients with 
PRA or genetic cataracts should not be bred 
and related animals should be examined. 
• Retinal detachment—restrict exercise until 
the retina is firmly reattached. • Calorie-
restricted diet—to prevent obesity owing to 
reduced activity level. • Cats with nutritionally 
induced retinopathy—ensure diet has 
adequate levels of taurine. • SARDS, PRA, 
optic nerve atrophy, and optic nerve 
hypoplasia—no effective treatment. 
• Cataracts, luxated lenses, and some forms 
of retinal detachment—best treated 
surgically.
• Depend on cause. • If workup is declined, 
infectious disease is unlikely, and the likely 
diagnosis is either SARDS or retrobulbar 
optic neuritis—consider systemic prednisolone 
(1–2 mg/kg/day PO for 7–14 days, then 
taper); may concurrently administer oral 
broad-spectrum antibiotic.Blind Quiet Eye

Canine and Feline, Seventh Edition  185
B
B
Do not use systemic corticosteroids or other 
immunosuppressive drugs with optic neuritis and 
retinal detachments that are infectious in origin.
Pretreatment with corticosteroids may mimic 
or mask liver enzyme changes in SARDS.
N/A
Oral azathioprine 1–2 mg/kg/day PO for 3–7 
days, then taper; may be used to treat 
immune-mediated retinal detachments if 
systemic corticosteroids are not effective; 
perform a CBC, platelet count, and liver 
enzyme every 1–2 weeks for the first 8 weeks, 
then periodically.
  FOLLOW-UP
• Repeat ophthalmic examinations—as 
required to ensure that ocular inflammation is 
controlled and, if possible, vision is maintained. 
• Recurrence of vision loss—common in optic neuritis; may occur weeks, months, or years 
after initial presentation.
• Death. • Permanent vision loss. • Loss of 
the eye. • Chronic ocular inflammation and 
pain. • Obesity from inactivity or as a sequela 
of SARDS.
• SARDS (dogs)—signs similar to those of 
hyperadrenocorticism. • Neurologic disease—
may note seizures, behavior or personality 
changes, circling or other CNS signs. 
• Cardiomyopathy (cats)—taurine deficiency.
• PRA and many cataracts—breed-specific ages 
of onset. • SARDS—tends to occur in older 
dogs. • Optic nerve hypoplasia—congenital.
N/A
Corticosteroids and immunosuppressive 
drugs may complicate pregnancy.SEE ALSO
Optic Neuritis and Papilledema.
• ALP = alkaline phosphatase. • CSF = 
cerebrospinal fluid. • PRA = progressive 
retinal atrophy. • SARDS = sudden acquired 
retinal degeneration syndrome.
• https://muffinshalo.com •http://www.
pepedog.com •https://www.akc.org/expert-
advice/health/seven-ways-to-keep-the-light-in-  
your-blind-dogs-life
Maggs DJ, Miller PE, Ofri R. Fundamentals 
of Veterinary Ophthalmology, 6th ed. St 
Louis, MO: Elsevier, 2018.
Rubin LF . Inherited Eye Disease in Purebred 
Dogs. Baltimore, MD: Williams & Wilkins, 
1989.
Author  Paul E. Miller
available onlineHistory, physical examination
Ophthalmic examination
Is the ocular media opaque? Check blood glucose
+/– lens extraction
CLEAR OCULAR MEDIA
Is the fundus normal?
YES
Pupillary light response
Abnormal
ERGNO
Retinal Detachment Retinal Degeneration
PRAOptic Neuropathy
Congenltal Hypoplasia
Optic NeuritisNORMAL
CNS blindness
NORMAL
Optic NeuritlsABNORMAL
SARDSLate SARDS• CBC
• Chemistry profile
• Urinalysis
• Deep fungal serology
• Systemic blood pressure
• Chest radiographs• CBC
• CSF tap
• CT/MRI
• Blood lead• CBC
• LDDST• CSF tap
• CT/MRI• Examine related
   animalsConsider
Consider
Rule out hypoxia
Consider
Consider• No Rx for anyPostinflammatoryDo not breedBlind Quiet Eye
Opaque ocular media
  Cataracts
Figure 1 .  (continued)  Blind Quiet Eye

186  Blackwell’s Five-Minute Veterinary Consult  
B
  BASICS
OVERVIEW
• Reaction to donor blood cells can result in 
minor (fever, urticaria) or major (hemolysis, 
anaphylactic shock) reactions, usually acute 
but can be delayed. • Can occur with admini  - 
stration of any blood‐derived product.
• Dogs and cats. • No sex predilection. • All 
ages affected.
SIGNS
Acute Nonhemolytic Reaction
• Fever, urticaria, erythema, pruritus (in 
10–25% of transfusions). • Septic shock from 
bacterial contamination of blood products. 
• T ransfusion‐associated circulatory overload 
(TACO)—dyspnea, cough, cyanosis (congestive 
heart failure). • T ransfusion‐associated acute 
lung injury (TRALI)—dyspnea, cyanosis. 
• Citrate toxicity—facial pruritis, weakness. 
• Hyperammonemia—encephalopathy.
Acute Hemolytic Reaction
• Occurs in 1–5% of transfusions. 
• Tachycardia, shock, anaphylaxis, death. 
• Collapse, lethargy, weakness. • Vomiting, 
diarrhea. • Pigmenturia, potential for 
pigmentary nephropathy. • Restlessness, 
hypersalivation, urticaria, facial swelling. 
• Hemolysis of transfused red blood cells 
(RBCs).
Delayed Hemolytic Reaction
Clinical signs of anemia may recur.
Delayed Nonhemolytic Reaction
Signs of blood‐borne disease (e.g., Babesia , 
Mycoplasma haemofelis , Ehrlichia ).
Cats and previously transfused dogs have 
higher risk of transfusion reactions.
• Anaphylaxis/immune reaction to donor 
cells, major histocompatibility complex 
(MHC) or plasma antigens, release of 
inflammatory mediators and pyrogens. • RBC 
membrane fragility (from depleted adenosine 
triphosphate [ATP]) can result in mechanical 
destruction during transfusion; degradation of 
ATP causes hyperammonemia in stored blood. 
• Contamination of blood can result from 
lack of aseptic collection or poor storage 
conditions. • TACO results from rapid 
transfusion or excessive transfusion volume. 
• Citrate toxicity causes hypocalcemia.
Acute Hemolysis
• Type II hypersensitivity reaction caused by 
naturally occurring or acquired antibodies 
against donor RBCs (cats have existing 
alloantibodies against other blood type, dogs 
require prior sensitization). • T ransfusion of 
damaged RBCs.Delayed Hemolysis
Immune reaction to RBC antigens (5–14 
days after transfusion).
T ransmission of blood‐borne disease.
  DIAGNOSIS
• Hemolysis—other hemolytic disease  
(e.g., immune‐mediated hemolytic anemia, 
Babesia , zinc toxicity). • Fever, hypotension—
infectious/inflammatory disease, contamination 
of IV catheter sites. • Urticaria/pruritis—
allergic reaction; avoid coadministration of 
medications during transfusion to distinguish 
drug vs. transfusion reaction. • Pigmenturia—
hematuria or myoglobinuria vs. hemoglobinuria.
Hemoglobinemia, leukocytosis, thrombocyto-
penia possible, bilirubinemia, pigmenturia 
(hemoglobin/bilirubinuria).
• Cross‐match to confirm incompatibility. 
• Bacterial culture or microscopic exam -
ination of blood may reveal contamination. 
• Centrifugation of donor blood may show 
  TREATMENT
• Acute, nonhemolytic reaction —stop 
transfusion: if signs resolve, restart at slower 
rate, if signs recur, discontinue transfusion; if 
dyspnea, supplemental oxygen; if volume 
overload/congestive heart failure, furosemide; 
animals with TRALI may require mechanical 
ventilation. • Acute, hemolytic reaction —stop 
transfusion and administer IV fluids to 
maintain blood pressure and treat shock; in 
hypotensive patients, administer isotonic 
crystalloids (20–30 mL/kg, repeat as 
necessary); epinephrine and vasopressor 
therapy for severe anaphylaxis.
• For anaphylaxis—IV crystalloid as above, 
epinephrine 0.01 mg/kg IV. • For urticaria, 
fever—diphenhydramine (1–2 mg/kg IM); 
dexamethasone sodium phosphate (0.1 mg/kg 
IV once). • If septic shock suspected—broad‐
spectrum IV antibiotics, IV fluid therapy. 
• Volume overload—furosemide 2–4 mg/kg 
IV, oxygen. • Hypocalcemia—calcium 
gluconate 50–150 mg/kg IV slowly (monitor 
ECG).  FOLLOW‐UP
• Check attitude, rectal temperature, and vital 
signs before, during, and after transfusion. • For 
acute hemolytic reactions or septicemia—
intensive monitoring and supportive care 
required. • Measure PCV or hematocrit 2 hours 
post transfusion, sooner if clinical signs warrant.
• Record any transfusion reaction in the 
medical file. • Pretransfusion testing: ∘ Screen 
donors for infectious disease. ∘ Blood type 
donors and recipients (imperative in cats). 
∘ Cross‐match patients receiving repeated 
transfusions. • Have standard transfusion 
protocols, dedicated storage for blood products. 
• T ransfusion administration should start 
slowly but be completed within 4 hours. 
• Leukoreduction of RBC‐containing products 
may decrease incidence of reactions. • Older 
stored blood more likely to result in reaction.
Fulminant hemolysis may cause acute renal 
failure, multiorgan dysfunction, coagulopa-
thies, and cardiac arrhythmias.
• Acute course in most animals; 
nonhemolytic reactions have good prognosis. 
• Prognosis guarded in animals with severe 
reactions or hemolysis.
SEE ALSO
Sepsis and Bacteremia.
• ATP = adenosine triphosphate. • MHC = 
major histocompatibility complex. • RBC = 
red blood cells. • TACO = transfusion‐
associated circulatory overload. • TRALI = 
transfusion‐associated acute lung injury.
Hann L, Brown DC, King LG, Callan MB. 
Effect of duration of packed red blood cell 
storage on morbidity and mortality in dogs 
after transfusion: 3,095 cases (2001–2010). 
J Vet Intern Med 2014, 28(6):1830–1837.
Maglaras CH, Koenig A, Bedard DL, 
Brainard BM. Retrospective evaluation of 
the effect of red blood cell product age on 
occurrence of acute transfusion‐related 
complications in dogs: 210 cases (2010–
2012). JVECC 2017, 27(1):108–120.
Wardrop KJ. Update on canine and feline blood 
donor screening for blood‐borne pathogens. J 
Vet Intern Med 2016, 30(1):15–35.
Author  Jörg Bucheler
Consulting Editor  Melinda S. CamusBlood Transfusion Reactions

Canine and Feline, Seventh Edition  187
B
  BASICS
OVERVIEW
• Cyanobacterial blooms can occur in fresh 
and brackish waters, and in backyard ponds 
where algal material is concentrated. 
• Nutrient‐rich runoff, increased water 
temperatures, and stagnant water conditions 
favor toxic bloom formation. • Blue‐green 
algae exposure can lead to acute hepato‐ or 
neurotoxicosis in animals and humans. • Skin 
irritation following exposure to cyanobacteria‐  
contaminated water may occur. • Hepatotoxic 
blue‐green algae poisonings are more 
frequently reported than neurotoxic algal 
intoxication. • Toxin‐producing 
cyanobacteria include Microcystis , Anabena , 
Aphanizomenon , Oscillatoria , Lyngbya , and 
Planktothrix  spp. • Microcystins are hepatotoxic 
blue‐green algae toxins that have been found 
worldwide. • Anatoxins, which include 
anatoxin‐a and anatoxin‐as, are neurotoxic 
blue‐green algae toxins.
• Dogs—no breed, sex, or age predilection. 
• Cats—no cases reported.
SIGNS
Hepatotoxic
• Diarrhea, weakness, shock. • Rapid 
progression to depression, coma, and death.
Neurotoxic
• Onset of rigidity and muscle tremors within 
minutes to a few hours after exposure. 
• Rapid progression to paralysis, cyanosis, 
and death.
Dermatotoxic
• Pruritus, erythema, urticaria. • Secondary 
skin infection.
• Access to and ingestion of toxin‐
contaminated water and/or algal material. 
• Exposure to dietary supplements containing 
the blue‐green algae Spirulina platensis  and 
Aphanizomenon flos aquae  that are contam­
inated with microcystins. • Blooms more 
common in nutrient‐rich water in warmer 
months. • Blooms concentrated through 
wind or by removal into containers. • Certain 
algae reside in the benthic zone, e.g., in 
sediment; dogs mouthing material such as 
rocks from sediment can be at risk.
  DIAGNOSIS
• Amanitins, xylitol, cycad palms, 
acetaminophen, manganese, pennyroyal oil, 
cocklebur. • Other causes of acute liver 
failure—infectious, metabolic, dietary.Neurotoxic
• Strychnine, metaldehyde, avitrol, pyrethrins/
pyrethroids, zinc phosphide, bromethalin. 
• Organophosphorus, carbamate, and 
organochlorine insecticides. • Penitrem A, 
methylxanthines. • Poisonous plants ( Brunfelsia  
spp., cyanide, oleander, poison hemlock). 
• Illicit substances (amphetamine and 
derivatives), ephedra‐containing compounds. 
• Neurotoxic mushrooms.
Other causes of pruritus—allergies, infec­
tious, parasitic, dietary, endocrine.
• Elevated serum liver enzymes—alanine 
transaminase (ALT), aspartate transaminase 
(AST), alkaline phosphatase (ALP), bilirubin. 
• Hypoalbuminemia. • Hypoglycemia.
Neurotoxic and Dermatotoxic
No specific changes.
Morphologic algal ID in suspect water, algal 
material, or stomach content. Positive ID 
confirms hazard but is not confirmatory for 
the toxin because toxicity is strain specific.
• Detection of algal material on fur or in 
stomach contents. • Analysis of stomach 
contents and water/algal source for microcystins.
• Detection of anatoxin‐a in gastric contents, 
urine, bile, and suspect source material. 
• Depressed blood cholinesterase activity 
with anatoxin‐as poisoning.
  TREATMENT
• No antidote available. • Rapid onset typically 
prevents timely therapeutic intervention. 
• Gastrointestinal decontamination with 
activated charcoal can be attempted, but efficacy 
not known. • Hepatotoxic—supportive care, 
close monitoring, and case‐specific IV fluids to 
correct electrolytes and hypoglycemia, vitamin 
K1, and plasma transfusions. • Neurotoxic—
supportive care and seizure control. 
• Dermatotoxic—supportive care and 
treatment for secondary skin infections.
• Activated charcoal—1 g/kg PO q6 ­8h until 
2–3 days post ingestion; mix activated charcoal 
in water at 1 g/5 mL of water. • IV fluids—
maintain hydration, induce diuresis, correct 
hypoglycemia. • Dextrose—50% dextrose 
1 mL/kg IV slow bolus (1–3 min). • Vitamin 
K1—0.5–1.5 mg/kg SC/IM q12h; 1–5 mg/kg 
PO q24h. • Blood products—dependent on hemostatic test results. • Diazepam (2–5 mg/
kg IV, repeat in 30 min if necessary) for seizure 
control. • Phenobarbital (2–5 mg/kg IV 
q6–12h) for seizure control. • Methocarbamol 
(55–220 mg/kg IV) for muscle relaxation.
Alternative Drugs
• S‐adenosylmethionine (SAMe)—antioxidant 
and hepatoprotectant; no data on efficacy in 
hepatotoxic cyanotoxin toxicosis available; 
dose 20 mg/kg PO q24h. • Ascorbic acid and 
cimetidine—hepatocyte protectors; no data 
on efficacy in hepatotoxic cyanotoxin 
poisoning available.  • N‐acetylcysteine (NAC)—  
antioxidant; no data on efficacy in hepatotoxic 
cyanotoxin toxicosis available; glutathione 
precursor that can be included in treatment 
regimen for acute hepatic failure at 140 mg/kg 
IV load, followed by 70 mg/kg IV q6h for 7 
  FOLLOW‐UP
• Hepatotoxic—liver enzymes/function, 
coagulation status. • Neurotoxic—
thermoregulation, respiratory function, 
blood gases.
• Deny access to water with visible algal 
blooms. • Remove algal blooms from ponds 
immediately and discard material safely.
• Prognosis poor to guarded for hepatotoxic 
and neurotoxic; good for dermatotoxic. 
• Rapid onset and progression; often lethal.
• ALP = alkaline phosphatase. • ALT = 
alanine transaminase. • AST = aspartate 
transaminase. • NAC = N‐acetylcysteine.
http://www.cdc.gov/habs
Bautista AC, Moore CE, Lin Y, et al. 
Hepatopathy following consumption of a 
commercially available blue‐green algae 
dietary supplement in a dog. BMC Vet Res 
2015, 11:136.
Puschner B, Bautista AC, Wong C. 
Debromoaplysiatoxin as the causative agent of 
dermatitis in a dog after exposure to freshwater 
in California. Front Vet Sci 2017, 4:50.
Authors  Birgit Puschner and Adrienne 
C. Bautista
available onlineBlue‐Green Algae Toxicosis

188  Blackwell’s Five-Minute Veterinary Consult  
B
  BASICS
OVERVIEW
• Paralytic illness caused by preformed 
neurotoxin produced by bacterium 
Clostridium botulinum  (Gram +, anaerobe) 
contained in uncooked food, carrion, and 
contaminated or improperly stored silage. 
• Most cases in dogs caused by Clostridium 
botulinum  neurotoxin serotype C; neurotoxin 
interferes with release of acetylcholine at 
neuromuscular junction, resulting in diffuse 
lower motor neuron signs. • Heavy molecular 
weight of the toxin seems to preclude its 
transfer to placenta.
Dogs (naturally infected) and cats (experiment­
ally infected except for one case report of 
natural Clostridium botulinum  type C 
SIGNS
• Signs appear a few hours to 6 days after 
toxin ingestion. • Other dogs living in the 
same environment may be affected. • Acute, 
symmetric, progressive weakness develops, 
starting in the pelvic limbs and ascending to 
the trunk, thoracic limbs, neck, and muscles 
innervated by the cranial nerves; severe 
tetraparesis or tetraplegia ensues.
• Possible increased or decreased heart rate.
• In severe cases—diaphragmatic respiration.
Neurologic Examination Findings
• Mental status—normal. • Cranial nerves— 
may reveal sluggish pupillary light reflexes 
(PLR), diminished palpebral reflexes, 
decreased jaw tone, decreased gag reflex, 
salivation, and dysphonia. • Gait and 
posture—a stiff, short ­stride gait (no ataxia) is 
initially observed until recumbence develops 
(usually within 12–24 hours). • Spinal 
reflexes—decreased to absent with decreased 
muscle tone (to atonia) and muscle atrophy. 
• Autonomic signs—mydriasis with decreased 
PLR, decreased lacrimation, ileus, and urine 
retention or frequent voiding of small 
volumes. • No hyperesthesia.
  DIAGNOSIS
• Acute canine polyradiculoneuritis 
(coonhound paralysis). • Myasthenia gravis.
• Tick bite paralysis. • Coral snake venom 
toxicity. • Dumb form of rabies. • Lasalocid 
(growth promoter in ruminants) toxicosis.
Usually normal.OTHER LABORATORY TESTS
• Definitive diagnosis is based on detection 
of botulinum toxin in serum, feces, vomitus, 
or ingested food sample; by neutralization 
test in small rodents; or by in vitro test that 
measures toxin antigenicity rather than 
toxicity. • Detection of anti ­C botulinum 
neurotoxin antibodies may help support 
clinical diagnosis.
IMAGING
Thoracic radiographs—possible megaesophagus 
and/or signs of aspiration pneumonia.
• Electromyography may reveal fibrillation 
potentials and positive sharp waves in affected 
muscles. • Motor nerve conduction velocity 
may be normal or decreased, with reduced 
amplitude of evoked muscle action potentials; 
compound muscle action potentials can be 
decreased after low ­frequency repetitive nerve 
stimulations.
  TREATMENT
• If recent ingestion—gastric lavage, 
cathartics (avoid agents containing 
magnesium), or enemas may be useful. 
• Mildly affected dogs recover over a period 
of several days with supportive treatment 
including physical therapy, frequent 
turning, good bedding (to prevent decubital 
sores), bladder care (catheterization), 
artificial tears (to prevent corneal ulceration), 
and feeding from an elevated position 
(when megaesophagus present). • Dogs 
with respiratory difficulties require 
intensive care monitoring with arterial 
blood gas, intermittent esophageal suction, 
alimentation by nasogastric or gastrotomy 
tube, and eventually ventilatory support.
• Type C antitoxin may cause anaphylaxis; 
not effective when the toxin is already fixed 
at the nerve ending. • Antibiotics are not 
recommended since they might increase the 
release of toxins through bacterial lysis or 
by promoting intestinal infection; to be 
used only if secondary infections occur.
Aminoglycosides, procaine penicillin, 
tetracyclines, phenothiazines, antiarrhythmic 
agents, and magnesium should be avoided 
(neuromuscular transmission blockade).  FOLLOW-UP
Monitor patients for respiratory failure, 
aspiration pneumonia, progressive lower 
motor neuron signs, urinary tract infection, 
and ocular complications.
• Prevent access to carrion and feed dogs 
cooked food. • Avoid contact with spoiled 
raw meat. • Samples should be refrigerated 
(not frozen) and manipulated with caution, 
since humans are also sensitive to the toxin.
• Respiratory failure and death in severe cases. 
• Aspiration pneumonia from megaesophagus 
and regurgitations. • Keratoconjunctivitis 
sicca and corneal ulceration. • Prolonged 
recumbence—pulmonary atelectasia and 
infection; decubital sores; urine scalding.
• Maximum severity of signs usually reached 
within 12–24 hours. • Neurologic signs disappear 
in reverse order of appearance; complete recovery 
usually occurs within 1–3 weeks, and requires the 
formation of new nerve terminals and functional 
neuromuscular junctions.
SEE ALSO
• Coonhound Paralysis (Acute 
Polyradiculoneuritis). • Myasthenia Gravis. 
• Snake Venom Toxicosis—Coral Snakes. 
• Tick Bite Paralysis.
Añor S. Acute lower motor neuron tetrapare­
sis. Vet Clin North Am Small Anim Pract 
2014, 44(6):1201–1222,
Barsanti J, Greene C, eds. Infectious Diseases 
of the Dog and Cat, 4th ed. St. Louis, MO: 
Saunders Elsevier, 2012, pp. 416–422.
Elad D, Yas ­Natan E, Aroch I, et al. Natural 
Clostridium type C toxicosis in a group of cats. 
J Clin Microbiol 2004, 42(11):5406–5408.
Lamoureux A, Pouzot ­Nevoret C, Escriou C. A 
case of type B botulism in a pregnant bitch. J 
Small Anim Pract 2015, 56(5):348–350.
Silva R, Martins R, Assis R, et al. Type C 
botulism in domestic chickens, dogs and 
black ­pencilled marmoset ( Callithrix 
penicillata ) in Minas Gerais, Brazil. 
Anaerobe 2018, 51:47–49.
Uriarte A, Thibaud J, Blot S. Botulism in 2 
urban dogs. Can Vet J 2010, 51:1139–1142.
Author  Hélène L.M. Ruel
Roberto Poma (deceased).Botulism

Canine and Feline, Seventh Edition  189
B
  BASICS
OVERVIEW
• T rauma with traction and/or severe 
abduction of a forelimb causes avulsion of 
nerve rootlets from their spinal cord attach- 
ment. • Ventral (motor) nerve roots are more 
susceptible than dorsal (sensory) roots. • It is 
important to rule out nerve root avulsions in 
traumatized animals that are not able to bear 
weight on a forelimb, especially before 
surgical repair of orthopedic injuries.
• Dogs and cats. • No age, sex, or breed 
SIGNS
• Depend on the extent and distribution of 
rootlet damage. • Motor signs—paresis/
weakness (partial damage) to paralysis 
(complete ventral root avulsion). • Sensory 
signs—decreased to absent pain perception 
(dorsal root damage). • Muscle atrophy—
begins within a week of injury. • Complete 
avulsion—spinal nerves C5 to T2; most 
common; combines cranial and caudal avulsion 
deficits. • Cranial avulsion—C5 to C7 nerves: 
supraspinatus and infraspinatus muscle atrophy, 
loss of shoulder and elbow movement flexion 
(dropped elbow), analgesia of craniodorsal 
scapula and medial forearm, possible diaphragm 
hemiplegia detected by fluoroscopy (phrenic 
nerve roots C5 to C7); if roots C8 to T2 are 
preserved, weight bearing remains almost 
normal. • Caudal avulsion—spinal nerves C7 
to T2: inability to bear weight with knuckling 
over dorsum of paw; if C5 to C7 are spared, the 
limb is held in a flexed position and there is 
analgesia distal to the elbow (except for a small 
area on the medial aspect of the forearm); T1 to 
T2 involvement causes an ipsilateral partial 
Horner’s syndrome (anisocoria only) and lack 
of ipsilateral cutaneous trunci reflex (reflex 
present contralaterally). • Bilateral avulsion—
rarely encountered, caused by a significant fall 
with sternal landing and splaying of limbs. 
• Over time, complications of self-trauma may 
occur as a result of paresthesia in the most 
severe cases.
T rauma—road accident; hung by foot; 
dragged; fall.
  DIAGNOSIS
• Brachial plexus trauma without avulsion—
rare; temporary deficit owing to root contusion (neurapraxia). • Brachial plexus 
tumor—usually chronic, progressive onset. 
• Brachial plexus neuritis or neuropathy—
rare, bilateral deficits, unknown etiology; 
acute onset; no trauma. • Fibrocartilaginous 
embolic myelopathy—deficits of ipsilateral 
hind limb and mild deficits of contralateral 
forelimb and hind limb are usually present. 
• Migrating foreign body – slow onset and no 
history of trauma. • Pure radial nerve 
paralysis caused by fracture of humerus or 
first rib—no nerve root sign. • Lateralized 
intervertebral disc protrusion.
IMAGING
CT or MRI—visualize lesion; rarely needed 
for diagnosis.
• Clinical—history of trauma with sudden 
onset of typical neurologic deficits. • Define 
involved spinal nerve roots—map motor and 
sensory deficits; note signs of Horner’s 
syndrome; determine if cutaneous trunci 
reflex is present. • Electromyography (EMG) 
and nerve conduction studies (NCS) may 
help further define deficits and detect signs of 
recovery—from 5–7 days post injury, EMG 
shows denervation in affected muscles.
• Ventral and dorsal root avulsions—
intradurally at level of root–spinal cord 
junction (most fragile area because it lacks 
protective perineurium). • Neuroma 
formation may develop over time on pial 
surface of spinal cord.
  TREATMENT
Appropriate Health Care
• No specific treatment. • Outcome depends 
on initial damage. • Amputation of limb—
may be necessary for patients showing 
complications (infections/self-mutilation, 
likely as a result of paresthesia) and no 
improvement. • Carpal fusion (arthrodesis) 
and transposition of biceps muscle tendon—
consider only with adequate function of 
triceps and musculocutaneous muscles.
Nursing Care
• Protective wrap or boot to protect distal 
paw if patient walks a lot/walks on rough 
surfaces—increased skin fragility and lack of 
protective reflexes due to sensory deficits can 
result in severe excoriations when animal 
walks on affected limb. • Early and sustained 
physical therapy—crucial to prevent severe 
muscle atrophy and tendon contraction to 
keep joints and muscles mobile during 
recovery of reversible injuries; passive range of motion, massage therapy. • Monitor 
noncomplicated cases for 4–6 months before 
considering amputation.
Prednisolone (prednisone)—1-week anti- 
inflammatory course may decrease early 
edema and favor healing of reversible injuries.
  FOLLOW-UP
• Skin excoriation and secondary infection—
from trauma to unprotected paw. • T rophic 
ulcers—thin, traumatized skin, especially over 
arthrodesis sites. • Paresthesia may lead to 
self-mutilation.
• Preserved pain sensation (dorsal roots 
intact)—suggests less severe injury to ventral 
nerve roots. • Cranial avulsion—better 
prognosis with preserved sensation to distal 
limb and ability to bear weight. • Complete 
avulsion—poor prognosis for recovery, 
amputation likely. • Rarely, mild cases may 
resolve after 2–3 months.
SEE ALSO
Polyneuropathies (Peripheral Neuropathies).
• EMG = electromyography. • NCS = nerve 
conduction studies.
Bailey CS. Patterns of cutaneous anesthesia 
associated with brachial plexus avulsions in 
the dog. JAVMA 1984, 185:889–899.
Braund KG. Neuropathic disorders. In: 
Braund KG, ed., Clinical Neurology in 
Small Animals: Localization, Diagnosis and 
T reatment. Ithaca, NY: IVIS, 2003. http://
www.ivis.org/advances/Vite/braund20b/
chapter_frm.asp.
Walmsley G, Scurrell E, Summers B, et al. 
Foreign body induced neuritis masquerad-
ing as a canine brachial plexus nerve sheath 
tumour. Vet Comp Orthop T raumatol 
2009, 22(5):427–429.
Author  Christine F . Berthelin-BakerBrachial Plexus Avulsion

B190  Blackwell’s Five-Minute Veterinary Consult  
B
  BASICS
Partial upper airway obstruction in brachy­
cephalic dogs and cats caused by any of the 
following: stenotic nares, overlong soft palate, 
everted laryngeal saccules, and laryngeal 
collapse. Hypoplastic trachea can also be 
present and worsen respiratory distress.
• In normal dogs, the upper airway accounts 
for 50–70% of total airway resistance. Brachy  ­ 
cephalic breeds have increased upper airway 
resistance due to stenosis of nares, aberrant 
formation of nasal conchae, and presence of 
nasopharyngeal turbinates. Skull bones are 
shortened in length but normal in width, and 
soft tissues are not proportionately reduced, 
resulting in redundant tissue and narrowed air 
passages. • Increased airway resistance leads to 
more negative intra ­airway pressures—may result 
in secondary eversion of laryngeal saccules, 
further elongation of palate, and laryngeal 
collapse. • Recruitment of pharyngeal dilator 
muscles (sternohyoid) becomes necessary to 
maintain airway patency; sleep apnea may occur 
secondary to relaxation of these muscles.
• Respiratory—respiratory distress, hypox­
emia, hypercarbia, hyperthermia, aspiration 
pneumonia, noncardiogenic pulmonary 
edema from airway obstruction. 
• Cardiovascular—cardiovascular collapse if 
complete airway obstruction or severe hyper ­ 
thermia occurs. • Gastrointestinal—may be 
reluctant to eat or drink; increased airway 
resistance can exacerbate hiatal hernia, 
gastroesophageal reflux, and esophagitis.
GENETICS
Brachycephalic head shape—inherited defect 
in development of skull bones perpetuated by 
selective breeding.
• Dogs—common in brachycephalic breeds.
• Cats—less commonly severe enough to 
require treatment.
Worldwide
Species
• Dogs—brachycephalic breeds (English 
bulldogs most common—up to 55% of 
breed, French bulldog, pug, Boston terrier); 
Norwich terriers and Cavalier King Charles 
spaniels affected by a variant of the syndrome.
• Cats—Persians and Himalayans.
• Young adults, most diagnosed by 2–3 years.
• If diagnosed later than 4 years, look for concurrent disease or exacerbating circumstances. 
• Laryngeal collapse reported in brachycephalic 
breed puppies as young as 6–7 months.
SIGNS
• Snoring, stridor, stertorous breathing.
• Tachypnea, frequent panting. • Coughing 
and gagging. • Difficulty eating and 
swallowing. • Ptyalism, regurgitation, and 
vomiting. • Syncope or collapse.
• Stridor and stertorous breathing. 
• Stenotic nares—medial collapse of lateral 
nasal cartilage. • Increased respiratory 
effort—retraction of the commissures of 
lips, open ­mouth breathing or constant 
panting, increased respiratory rate, abduction 
of forelimbs, increased abdominal 
component of respiration, recruitment of 
secondary muscles of respiration. • In severe 
distress, may see paradoxical abdominal 
movement, inward collapse of intercostal 
muscles during inspiration, orthopnea, and 
cyanosis. Hyperthermia may be present.
CAUSES
• Inherited or congenital defects in 
conformation. • Elongated soft palate—over 
90% of surgical cases in dogs. • Stenotic 
nares—about 50% of dogs; most common 
defect in cats. • Aberrant formation of rostral 
and caudal nasal conchae. • Presence of 
nasopharyngeal turbinates (20% of dogs) 
and 100% of English bulldogs. • Laryngeal 
disease—everted laryngeal saccules ( >50% 
of dogs) and/or laryngeal collapse ( ∼10% 
of dogs).
• Breed. • Obesity—worsens airway 
obstruction, associated with poorer outcome 
postoperatively, and may contribute to gastro  ­ 
esophageal reflux and aspiration pneumonia. 
• Excitement and/or warm, humid weather—
increased panting can lead to airway edema, 
further compromise of the lumen, and 
hyperthermia. • Exercise—dogs are often 
exercise intolerant due to airway compromise 
and hypoxia. • Sedation—relaxation of 
muscles of pharynx and palate can cause 
complete airway obstruction. • Respiratory 
infection or concurrent pulmonary disease—
will cause further respiratory compromise. 
• Endocrine disease (hypothyroidism and 
hyperadrenocorticism)—could worsen weight 
gain and panting.
  DIAGNOSIS
• Foreign bodies of nasopharynx, larynx, or 
trachea. • Infection—upper respiratory infection, nasopharyngeal abscess. 
• Neoplasia obstructing the nasopharynx, 
glottis, larynx, or trachea. • Laryngeal 
paralysis. • Pharyngeal mucocoele. 
• Nasopharyngeal polyp or cyst.
CBC—usually normal, but polycythemia 
can occur with chronic hypoxia, and 
leukocytosis if concurrent infection or 
severe stress.
• Arterial blood gas—to diagnose respiratory 
acidosis and hypoxemia, and response to 
oxygen supplementation. • Pulse oximetry—
to diagnose hypoxemia.
IMAGING
• If stable, cervical and thoracic radiographs 
recommended. • Cervical radiographs may 
show thickened, elongated soft palate and 
suggest tracheal hypoplasia. • Thoracic 
radiographs can reveal aspiration pneumonia, 
pulmonary edema, air in esophagus, and 
hypoplastic trachea (TD/TI = tracheal 
diameter at the level of thoracic inlet/thoracic 
inlet distance, which is the distance from the 
sternum to the ventral surface of TI. A ratio 
<0.13 in bulldogs and <0.16 in other brachy  ­ 
cephalic breeds suggests hypoplastic trachea).
Fluoroscopy
Gives information about degree of dynamic 
pharyngeal obstruction by palate and 
concurrent disease such as collapsing 
trachea (uncommon in brachycephalic 
dogs).
Laryngoscopy/Pharyngoscopy
• Performed under general anesthesia. • Due 
to risk of airway obstruction, owner should 
be prepared for surgical intervention if 
deemed necessary. • Overlong soft palate 
extends more than just a few millimeters 
beyond tip of epiglottis and hangs down 
into glottis. • Soft palate is often thickened 
and inflamed. • May have inflammation and 
edema of arytenoid cartilages. • Everted 
laryngeal saccules are diagnosed by visual­
izing two smooth, round, glistening masses 
in ventral half of laryngeal opening—they 
often obscure visualization of vocal folds. 
• Laryngeal collapse can also be seen. 
• Flexible endoscopy with retroflexed view 
of nasopharynx can detect nasopharyngeal 
turbinates.
Tracheoscopy
• Can reveal hypoplastic trachea with overlap 
of dorsal tracheal rings and dorsal tracheal 
membrane. • Collapsing trachea can also be 
diagnosed.
CT Scan
Can identify and grade aberrant nasopharyngeal 
turbinates.Brachycephalic Airway Syndrome

Canine and Feline, Seventh Edition  191
BB
  TREATMENT
• Surgery recommended for patients with 
significant clinical signs or to prevent 
progressive respiratory dysfunction. • Severe 
respiratory distress requires rapid intervention 
including O2 supplementation, cautious use of 
antianxiety medication. • If hyperthermic, cool 
via convective losses by wetting patient with 
cool water and placing fan to blow over them; 
administer IV fluids, up to a shock rate if 
extremely hyperthermic (T° >106 °F [41 °C]). 
• If complete airway obstruction, immediate 
orotracheal intubation and/or temporary 
tracheostomy is indicated. • Dexamethasone 
sodium phosphate can be administered 
(0.1 mg/kg IV) to reduce inflammation.
• Patients require 24 ­hour monitoring 
because of risk of acute airway obstruction 
and death. • Monitor respiratory rate, effort, 
heart rate, pulse quality, mucous membrane 
color, capillary refill time, temperature, and 
other physical parameters before and after 
surgery. • Pulse oximetry and arterial blood 
gases, depending on severity of condition. 
• Administer IV fluids at maintenance rate 
and minimize handling and stress. • O2 
therapy and cooling as necessary.
ACTIVITY
Usually self ­limited.
DIET
• Weight loss is recommended if overweight.
• For obese, stable patients, weight loss is 
recommended prior to surgery.
• Avoidance of risk factors is critical. • Inform 
owners that dogs with brachycephalic airway 
syndrome are at increased anesthetic risk, 
especially if obese, or have cardiac disease or 
aspiration pneumonia. • Inform owners that 
surgery often improves but does not normalize 
airway.
• Evaluation for elongated soft palate 
performed under general anesthesia when 
patient is stable. • Temporary tracheostomy 
can be placed to facilitate exposure or to treat 
airway obstruction. • Stenotic nares are 
corrected by resection of a wedge of the 
dorsolateral nasal cartilage and planum; 
hemorrhage is controlled with pressure 
followed by closure of the surgical wound with 
3 or 4 sutures of 3 ­0 or 4 ­0 absorbable suture 
material. • Elongated soft palate is resected 
using scissors, carbon dioxide laser, or bipolar 
sealing device; remove only enough to allow 
contact of center of soft palate with tip of 
epiglottis. • Sacculectomy performed by 
grasping tissue with Allis tissue forceps and trimming all mucosal tissue with curved 
scissors. • Severe laryngeal collapse might 
require cricoarytenoid and thyroarytenoid 
caudolateralization or permanent tracheostomy.
• Dexamethasone sodium phosphate for 
12–24h pre ­ or postoperatively at 0.1 mg/kg 
IV q12–24h to reduce edema and inflammation. 
• Broad ­spectrum antibiotics indicated if 
aspiration pneumonia present until culture and 
sensitivity results obtained. • Omeprazole 
0.7 mg/kg q24h or pantoprazole 1 mg/kg 
q24h, cisapride 0.2 mg/kg q8h, and sucralfate 
0.5–1 g q12h for dogs with concurrent 
esophagitis, gastritis, and/or duodenitis.
Overuse of steroids can lead to panting, 
weight gain, and gastrointestinal ulceration, 
which can exacerbate signs of brachycephalic 
airway syndrome.
Sedation should be used with caution because 
of risk of upper airway obstruction with 
muscle relaxation.
  FOLLOW-UP
Postoperatively, 24 ­hour monitoring to 
observe for airway swelling and obstruction 
that may require temporary tracheostomy.
• Selection by breeders for dogs without 
severe conformational changes—difficult 
because breed standards encourage these. 
• Avoid risk factors, particularly weight gain.
• Hyperthermia and heat stroke. • Aspiration 
pneumonia. • Death in about 10% of 
patients from airway disease. • Most common 
postoperative complication is airway swelling 
and obstruction within first 24 hours, may 
necessitate temporary tracheostomy. 
• Continued respiratory difficulty after 
corrective surgery. • Excessive resection of 
palate resulting in nasal aspiration of food 
contents due to inability to close pharynx 
during swallowing. • Progressive laryngeal 
collapse resulting in need for permanent 
tracheostomy.
• Prognosis good for improvement in 
breathing (80% or more have good to excellent 
results), but airway still abnormal. • Prognosis 
better for dogs other than English bulldogs and for dogs that have correction of both stenotic 
nares and elongated soft palate. • Without 
surgery, prognosis poor due to continued 
progression of acquired components of 
brachycephalic airway syndrome. • Lifelong 
avoidance of risk factors recommended.
• Aspiration pneumonia. • Heat stroke. 
• Hiatal hernia. • Hypoplastic trachea.
Older dogs may have a worse outcome 
postoperatively, but most have some 
improvement.
Enlarged abdomen and pressure on the 
diaphragm in the pregnant bitch can further 
compromise respiratory function by 
decreasing tidal volume.
https://www.acvs.org/small ­animal/
brachycephalic ­syndrome
Ginn JA, Kumar MSA, McKiernan BC, 
Powers BE. Nasopharyngeal turbinates in 
brachycephalic dogs and cats. J Am Anim 
Hosp Assoc 2008, 44(5):243–249.
Monnet E. Brachycephalic airway syndrome. 
In: Slatter D, ed., Textbook of Small Animal 
Surgery, 3rd ed. Philadelphia, PA: Saunders, 
2003, pp. 808–813.
Poncet CM, Dupre GP , Freiche VG, Bouvy 
BM. Long ­term results of upper respiratory 
syndrome surgery and gastrointestinal tract 
medical treatment in 51 brachycephalic 
dogs. J Small Anim Pract 2006, 
47(3):137–142.
Poncet CM, Dupre GP , Freiche VG, et al. 
Prevalence of gastrointestinal tract lesions in 
brachycephalic dogs with upper respiratory 
syndrome: clinical study in 73 cases (2000–
2003). J Small Anim Pract 2005, 46:273–279.
Riecks TW, Birchard SJ, Stephens JA. Surgical 
correction of brachycephalic syndrome in 
dogs: 62 cases (1991–2004). J Am Vet Med 
Assoc 2007, 230(9):1324–1328.
White RN. Surgical management of laryngeal 
collapse associated with brachycephalic 
airway obstruction syndrome in dogs. 
J Small Anim Pract 2012, 53:44–50.
Authors  David A. Puerto and Lori S. 
Waddell
available online(continued)  Brachycephalic Airway Syndrome

192  Blackwell’s Five-Minute Veterinary Consult  
BBrain Injury
  BASICS
• T raumatic—external forces. • Nontraumatic—  
hypoxia, metabolic disorders, vascular disruption, 
infection, toxicity, neoplasia. • Primary—direct 
initial insult when tissue and vessels are 
stretched, compressed, or torn. • Secondary—
alterations of brain vasculature and tissue 
following primary injury.
• Acceleration, deceleration, and rotational 
forces traumatize brain tissue. • The brain has 
high oxygen and glucose requirements; 
reduced blood flow puts it at great risk for 
hypoxia. • Oxygen delivery dependent on 
cerebral blood flow (CBF) and cerebral 
perfusion pressure (CPP) (= mean arterial 
pressure [MAP] – intracranial pressure [ICP]). 
• Intracranial bleeding, edema (vasogenic and 
cytotoxic), vasodilation, and/or vasospasms 
increase ICP , causing low CBF , ischemia, brain 
swelling, and herniation; slow, progressive 
increase in ICP better tolerated than small, 
acute rise. • Hypotension, hypoxia—major 
contributors to secondary injury.
• Nervous—altered mentation, cranial nerve 
deficit, seizures, twitching, postural changes. 
• Cardiovascular—arrhythmia. • Endocrine/
metabolic—alteration in antidiuretic hormone 
(ADH) release and sodium concentration; central 
temperature dysregulation; insulin resistance; 
depletion of cortisol. • Ophthalmic—changes in 
eye position, eye movements, pupillary light 
reflex, papilledema. • Respiratory—hyper‐ or 
hypocapnea; abnormal breathing patterns; 
neurogenic pulmonary edema.
• Head and neck injuries found in up to 34% 
of dogs and cats suffering blunt force trauma. 
• Head trauma reported in up to 25% of dogs 
with severe blunt force trauma and in 50% of 
dogs and cats injured by motor vehicles and 
crush injuries. • Additional causes—
penetrating injuries, fall from heights, human‐  
inflicted trauma. • Parenchymal and 
extradural hematomas found in 10% of dogs 
and cats with signs of mild head injury and in 
up to 80% with severe head injury.
Species
SIGNS
• Determine cause—trauma, cardiac arrest, 
heart failure, hypertension, toxins, vascular 
event, coagulopathy, severe respiratory 
compromise, prolonged seizures, hypoglycemia, 
jaundice. • Decline in neurologic condition—implies progression from intracranial bleeding, 
cerebral edema, ischemia. • Seizure activity—
cerebral or diencephalon involvement.
• Evidence of head trauma—open wounds, 
epistaxis, blood in ear canal. • Cardiac or 
respiratory insufficiency—hypoxia, cyanosis, 
hypoventilation. • Poor perfusion—weak pulse, 
pale mucous membranes. • Skull palpation—
fracture, open fontanelle. • Sustained 
bradycardia—midbrain, pontine, or medullary 
lesion. • Cushing reflex—bradycardia and 
hypertension. • Ecchymosis, petechiae, retinal 
hemorrhages, or distended vessels—hypertension, 
coagulopathy. • Papilledema—cerebral edema. 
• Retinal detachment—infectious, neoplastic, 
or hypertensive cause.
Mental Status
• Level of consciousness and cranial nerve 
deficits—cerebral cortex (better prognosis), 
midbrain/brainstem, or multifocal. • Postural 
changes—decerebrate rigidity with midbrain 
lesion; decerebellate rigidity with cerebellar 
lesion. • Peracute focal deficits—vascular or 
neoplastic causes.
Pupillary Light Reflexes
• Miotic responsive pupils—cerebral or 
diencephalic lesion (rule out traumatic 
uveitis, Horner’s syndrome). • Pinpointed 
unresponsive pupils—diencephalic, pontine, 
or medullary lesion. • Dilated unresponsive 
pupil(s) or midpoint fixed unresponsive 
pupils—midbrain lesion.
Cranial Nerves
• Normal with altered mentation—
cerebrum/diencephalic lesion. • CN II—loss 
of menace and dazzle response with dilated 
unresponsive pupils; cranial forebrain. • Loss 
of physiologic nystagmus—brainstem lesion. 
• CN III—midbrain lesion. • CN V–XII—
pontine or medullary lesion.
Respiratory Patterns
• Cheyne‐Stokes—severe diffuse cerebral or 
diencephalon lesion. • Hyperventilation—
midbrain lesion. • Ataxic or apneustic—
CAUSES
• T rauma. • Prolonged hypoxia or ischemia. 
• Prolonged shock. • Severe hypoglycemia. 
• Prolonged seizures. • Severe hyper‐ or 
hypothermia. • Alterations in serum osmolality. 
• Toxins. • Neoplasia. • Hypertension.  
• Hemorrhage. • Inflammatory, infectious, 
immune‐mediated diseases. • Thiamin 
deficiency. • Hydrocephalus. • Parasitic 
• Free‐roaming—trauma, toxins. 
• Coexisting cardiac, respiratory, hematologic, 
hepatic disease. • Diabetes mellitus—
insulin therapy.  DIAGNOSIS
Systemic causes of altered states of conscious-
ness or central vestibular signs—metabolic 
disease; toxins; drugs; infection.
• Reflect systemic effects of neurologic signs. 
• Alterations in serum sodium suggest central 
ADH abnormalities.
• Arterial blood gas. • Coagulation profile. 
• Infectious disease titers.
IMAGING
• Skull radiographs—detect fractures, lytic 
lesion. • CT—detect acute hemorrhage, 
infarcts, fractures, lytic lesion, penetrating 
foreign bodies, hydrocephalus, herniation. 
• MRI—detect cerebral edema, hemorrhage, 
mass, hydrocephalus, infiltrative diseases, 
inflammation, herniation, fractures. 
• Ultrasound optic disk—more than 3 mm 
diameter may be associated with brain edema.
• ECG—detects arrhythmias. • BP—assess 
perfusion. • Cerebrospinal fluid (CSF) 
analysis—if cause unknown and no contra  - 
indications.
• Brain edema, inflammation. • Herniation. 
• Hemorrhage. • Hydrocephalus. • Infarct. 
• Laceration, contusion. • Hematoma. • Skull 
fracture, lytic lesion. • Necrosis. • Apoptosis.
  TREATMENT
• Goals of therapy—support oxygenation and 
ventilation; maintain BP and CPP; decrease 
ICP; decrease cerebral metabolic rate. 
• Maintain systolic BP >90 mmHg and 
partial pressure of carbon dioxide (PCO2) at 
35–40 mmHg; with suspected elevated ICP , 
hyperventilation to 32–35 mmHg. 
• Maintain partial pressure of oxygen (PaO2) 
>60 mmHg, arterial oxygen saturation (SaO2) 
>90%, peripheral oxygen saturation (SpO2) 
>94%. • Avoid cough or sneeze reflex during 
intubation or nasal oxygen supplementation; 
lidocaine (dogs: topical and 1–2 mg/kg IV) 
before. • Do not compress jugular veins. 
• Orotracheal intubation if gag reflex lost.
• Aggressive therapy for midbrain/brainstem 
lesion or declining neurologic signs. • Overzealous 
fluid resuscitation can contribute to brain 
edema. • Small‐volume fluid resuscitation 
techniques to maintain systolic BP >90 mmHg 
with normal heart rate. • Combination of

Canine and Feline, Seventh Edition  193
B
isotonic crystalloids (10–20 mL/kg increments) 
with hydroxyethyl starch (5 mL/kg increments) 
over 5–8 minutes. • Avoid hypertension. 
• Level head with body or elevate head and 
neck to 20° angle. • Keep airway unobstructed; 
use suction and humidify if intubated; 
hyperoxygenate, consider IV lidocaine prior to 
suctioning. • Lubricate eyes. • Reposition every 
2–4 hours to avoid hypostatic pulmonary 
congestion, pressure sores. • Prevent fecal/urine 
soiling. • Maintain normal body temperature. 
• Maintain hydration with balanced crystalloid 
solution. • Rehabilitation exercises.
ACTIVITY
• Restricted. • Consult rehabilitation specialist 
for appropriate exercises to maintain muscle tone.
• Neurologic signs may worsen before improving. 
• Neurologic recovery may not be evident for 
several days; possibly >6 months for residual 
neurologic deficits. • Serious systemic 
abnormalities contribute to CNS instability.
Depressed skull fracture, penetrating foreign 
body, uncontrollable ICP elevation (insuf-
ficient CSF drainage, hematoma/mass 
evacuation, herniation).
Elevated ICP
• Ensure systolic BP >90 mmHg; lower ICP by 
hyperventilation, drug therapy, drainage of CSF 
from ventricles, or surgical decompression. 
• 7% hypertonic saline—2–4 mL/kg IV. 
• Furosemide—0.75 mg/kg IV; may decrease 
CSF production. • Mannitol—0.5–1 g/kg IV 
bolus repeated at 2h intervals 3–4 times in 
dogs, and 2–3 three times in cats; repeated 
doses must be given on time; improves CBF 
and lowers ICP; may exacerbate hemorrhage. 
• Glucocorticosteroids—no benefit in acute 
management and long‐term outcome in 
human traumatic brain injury (TBI); anti‐
inflammatory doses (prednisone 1 mg/kg/day) 
may be of benefit with brain edema related to 
intracranial neoplasia and infectious meningo -
encephalomyelitis (MEM); immunosuppressive 
doses (2 mg/kg/day) in combination with 
additional immunosuppressive drugs in 
immune‐mediated MEM. • Provide analgesia/
sedatives (e.g., fentanyl 3–5  μg/kg IV, then 
3–5 μg/kg/h CRI ± lidocaine 3–5 mg/kg/h) as 
indicated; avoid agents that can reduce CPP . 
Avoid ketamine with obstructive intracranial 
lesions. • Thrashing, seizures, or uncontrolled 
motor activity—diazepam CRI (0.5–1 mg/kg/h), 
midazolam CRI (0.2–0.4 mg/kg IV), or propofol 
(3–6 mg/kg IV titrated to effect; 0.1–0.6 mg/
kg/min CRI); monitor for hypotension; 
intubate if unable to protect airway.  • Levetiracetam—20–30 mg/kg IV/IM/PO/
rectal q8h if seizure activity.
Other
• Reducing cerebral metabolic rate with heavy 
sedation using dexmedetomidine (3 μg/kg slow 
bolus followed by 3–7 μg/kg/h CRI IV) with 
ketamine (1 μg/kg slow bolus followed by 1 μg/
kg/h CRI IV) with uncontrolled seizures or 
propofol (2–4 mg/kg IV then 0.1–0.4 mg/kg/
min); must intubate and support blood pressure, 
oxygenation, and ventilation. • Cooling patient 
to 32–33 °C (89–91 °F) for 48h may provide 
cerebral protection when administered within 6 
hours of global ischemia or severe brain injury. 
• Glucose regulation. • Careful nasogastric tube 
feeding for early trickle flow feeding; cisapride 
(0.5 mg/kg PO q8–12h) and metoclopramide 
(1–2 mg/kg/day) may promote gastrointestinal 
motility. • Desmopressin for refractory hyper  - 
natremia; emergency dosage not established for 
animals (dogs: 4  μg topical conjunctival q12h; 
cats: 5  μg SC q12h).
Drugs that cause hypertension, hypotension, 
hyperexcitability, or increase in metabolic rate.
• Avoid hypotension, hypoxemia, hyper -
tension, hyperglycemia, hypoglycemia, 
hypernatremia, hypo‐ or hypervolemia. 
• Keep head and neck above plane of body. 
• Do not compress jugular veins. 
• Furosemide, mannitol, and hypertonic 
saline—can cause hypovolemia and hypo -
tension. • Maintain PCO2 >32 mmHg; avoid 
hyperventilation in the first 24–8h and do 
not perform therapeutic hyperventilation 
(32–35 mmHg) for extended periods ( >48h).
  FOLLOW‐UP
• Repeated neurologic examinations—
deterioration warrants aggressive therapeutic 
intervention. • BP—maintain systolic BP 
>90 mmHg. • Blood gases, pulse oximetry, 
end‐tidal CO2—to assess need for oxygen 
supplementation or ventilation. • Blood 
glucose—avoid severe persistent hyperglycemia 
and hypoglycemia. • ECG—arrhythmias 
may affect perfusion, oxygenation, and CBF . 
• ICP—to detect elevations and monitor 
response to therapy.
Keep pets in a confined area or leashed.
• Seizures. • Brain herniation. • Intracranial 
hemorrhage. • Progression from cerebral cortical 
to midbrain signs. • Malnutrition. • Aspiration 
pneumonia. • Hypostatic pulmonary 
congestion. • Corneal desiccation. • Urine 
scalding. • Airway obstruction from mucus. • Arrhythmias. • Hypotension. • Hypernatremia. 
• Hypokalemia. • Respiratory failure. • Residual 
neurologic deficits. • Death.
• Young animals, minimal primary brain 
injury, secondary injury consisting of cerebral 
edema—best prognosis. • No deterioration 
for 48 hours—better prognosis. • Rapid 
resuscitation of systolic BP to >90 mmHg 
and avoiding hypoxemia—better neurologic 
outcome. • Modified Glasgow Coma Score 
may offer prognostic insight.
SYNONYMS
• Head trauma. • TBI.
SEE ALSO
Stupor and Coma.
• ADH = antidiuretic hormone. • CBF = 
cerebral blood flow. • CPP = cerebral perfusion 
pressure. • CRI = continuous rate infusion 
• CSF = cerebrospinal fluid. • ICP = intracranial 
pressure. • MAP = mean arterial pressure. 
• MEM = meningoencephalomyelitis. • PaO2 = 
partial pressure of oxygen. • PCO2 = partial 
pressure of carbon dioxide. • SaO2 = arterial 
oxygen saturation. • SpO2 = peripheral oxygen 
saturation. • TBI = traumatic brain injury.
http://www.traumaticbraininjury.com
Dewey CW, Downs MO, Aron DN, et al. 
Acute traumatic intracranial haemorrhage 
in dogs and cats. Vet Comp Orthop 
T raumatol 1993, 6:29–35.
Dewey CW, Fletcher DJ. Head trauma 
management. In: Dewey CW, ed., A Practical 
Guide to Canine and Feline Neurology, 2nd 
ed. Ames, IA: Wiley, 2008, pp. 221–235.
Fletcher D, Syring R. T raumatic brain injury. 
In: Silverstein D, Hopper K, eds., Small 
Animal Critical Care Medicine. St. Louis, 
MO: W.B. Saunders, 2014, pp. 723–727.
Freeman C, Platt SR. Head trauma, In: Platt 
SR, Garosi LS, eds., Small Animal 
Neurological Emergencies. London: 
Manson, 2012, pp. 363–382.
Sande A, West C. T raumatic brain injury: a 
review of pathophysiology and management. 
J Vet Emerg Crit Care 2010, 20:177–190.
Author  Elke Rudloff
Rebecca Kirby.
available online(continued)  Brain Injury

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  BASICS
• Brain tumors of cats and dogs may be 
classified as either primary or secondary, 
depending on the cell type of origin. 
• Primary brain tumors originate from cells 
normally found within the brain and meninges, 
including the neuroepithelium, lymphoid 
tissues, germ cells, endothelial cells, and 
malformed tissues. • Secondary tumors are 
either neoplasms that have reached the brain 
by hematogenous metastasis from a primary 
tumor outside the nervous system, or 
neoplasms that affect the brain by local 
invasion, or extension, from adjacent 
non-neural tissues such as bone. • Pituitary 
gland neoplasms (adenomas or carcinomas) 
and tumors arising from cranial nerves (e.g., 
nerve sheath tumor of trigeminal, oculomotor, 
or vestibulocochlear nerves) are considered 
secondary brain tumors.
• Brain tumors result in cerebral dysfunction 
by causing both primary effects, such as 
infiltration of nervous tissue or compression 
of adjacent anatomic structures, and 
secondary effects, such as hydrocephalus. 
• Additional primary effects include 
disruption of cerebral circulation and local 
necrosis, which may result in further damage 
to neural tissue. • The most important 
secondary effects of a primary brain tumor 
include disturbance of cerebrospinal fluid 
(CSF) flow dynamics, elevated intracranial 
pressure (ICP), cerebral edema, or brain 
herniation. • Secondary effects usually are 
more diffuse or generalized in their clinical 
manifestations and may mask the precise 
location of a focal intracranial lesion.
Nervous (brain).
GENETICS
• An unusually high incidence of 
meningiomas has been reported in cats with 
mucopolysaccharidosis type I. • Specific 
genetic factors associated with breed 
predisposition have not been identified. 
• Brachycephaly provisionally has been 
associated with the SMOC -2 and 
thrombospondin-2  genes on canine 
chromosome 1, and a component of glioma 
susceptibility provisionally has been mapped 
to a region on canine chromosome 2. 
• Molecular and genetic classification of brain 
tumors may permit targeted therapies in the 
future.
• Brain tumors appear to be more common 
in dogs than in other domestic species. 
• Reported incidence in dogs is 10–20 per 100,000 animals, or 1–3% of all deaths where 
necropsy was done. • Primary nervous system 
tumors in dogs account for 60–80% of all 
such tumors reported in domestic animals 
(10–20% in cats; 10–20% in other species). 
• The most common sites for neoplasia to 
occur in immature dogs ( <6 months), in 
decreasing order, are the hematopoietic 
system, brain, and skin. • Reported incidence 
in cats is 3.5/100000.
• Meningiomas occur most frequently in 
dolichocephalic breeds of dog. • Glial cell 
tumors and pituitary tumors occur commonly 
in brachycephalic breeds of dog. • Canine 
breeds overrepresented include boxer, golden 
retriever, Doberman pinscher, Scottish terrier, 
and Old English sheepdog. • There does not 
appear to be a breed predisposition for 
development of brain tumors in cats.
• Brain tumors occur in dogs and cats of any 
age. • Most frequent in older dogs, with 
greatest incidence in dogs >5 years of age. 
• Median age for diagnosis of meningiomas, 
gliomas, and choroid plexus tumors in dogs 
has been reported as 10–11 years, 8 years, and 
5–6 years, respectively.
Older male cats appear to be most susceptible 
to meningiomas.
SIGNS
• Vary with tumor location. • The most 
frequently recognized clinical sign associated 
with a brain tumor of a dog or cat is seizures, 
particularly should first seizure occur after 5 
years of age. • Other clinical signs frequently 
associated with brain tumor are abnormal 
behavior and mentation, visual deficits, 
circling, ataxia, head tilt, and cervical spinal 
hyperesthesia. • Signs that result from disease 
in given location in nervous system are 
similar, regardless of precise cause. • On basis 
of signalment, history, and results of complete 
physical and neurologic examinations, it is 
possible to localize a problem to the brain 
and, in some cases, to determine the approx  - 
imate location.
CAUSES
• Uncertain. • Dietary, environmental, 
genetic, chemical, viral, traumatic, and 
immunologic factors may be considered.
  DIAGNOSIS
Categories of disease that may result in 
clinical signs similar to those of a brain tumor 
include congenital disorders, infections, immunologic and metabolic disorders, 
toxicities, nutritional disorders, trauma, 
vascular disorders, degeneration, and 
idiopathic disorders.
The major objective in the completion of 
these tests is to eliminate extracranial causes 
for signs of cerebral dysfunction.
N/A
IMAGING
• Survey radiographs of the thorax and 
abdominal ultrasound—to rule out primary 
malignancy elsewhere in body. • Skull 
radiographs—of limited value; may detect 
neoplasms of skull or nasal cavity that involve 
brain by local extension. • Occasionally, lysis 
or hyperostosis of skull may accompany 
primary brain tumor (e.g., meningioma of 
cats), or there may be radiographically visible 
mineralization within a neoplasm. • CT—
provides accurate determination of presence, 
location, size, and anatomic relationships of 
many intracranial neoplasms. • MRI—
considered superior to CT in localization and 
characterization of most brain tumors.
CSF Analysis
• CSF—may help to rule out inflammatory 
causes of cerebral dysfunction: in some cases 
may support diagnosis of brain tumor. • Care 
should be used in collection of CSF , because 
increased ICP may be present in association 
with brain tumor, and pressure alterations 
associated with CSF collection may lead to 
brain herniation. • CSF collection usually 
delayed until advanced imaging has been 
completed to evaluate factors such as presence 
of cerebral edema or hemorrhage. • In 
general, increased CSF protein content and 
normal to increased CSF white blood cell 
count have been considered “typical” of a 
brain neoplasm.
Biopsy
• Cytologic evaluation of smear preparations 
from biopsy tissue, rapidly fixed in 95% 
alcohol and stained with hematoxylin and 
eosin, may be done within minutes of biopsy 
collection. • Tissue biopsy remains sole 
method available for definitive diagnosis of 
brain tumor type in cats or dogs, and is 
essential consideration prior to any type of 
therapy. • Biopsy not always attempted 
because of practical considerations, such as 
cost and morbidity. • CT-guided stereotactic 
biopsy systems provide relatively rapid and 
extremely accurate means of tumor biopsy, 
with low rate of complications.
• Classification of CNS tumors in dogs and 
cats primarily is based on the characteristics 
of their constituent cell type, pathologic Brain Tumors

Canine and Feline, Seventh Edition  195
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B
behavior, topographic pattern, and secondary 
changes present within and surrounding the 
tumor. • Meningioma is most common 
intracranial neoplasm of dogs and cats. 
• Classification of glial subset of neuroepi -
thelial tumors is based on predominant cell 
type (e.g., astrocyte or oligodendrocyte).
Dogs
• Embryonal tumors have been consolidated 
under single term “primitive neuroecto -
dermal tumors” (or PNETs) to accommodate 
their anaplastic nature. • Brain tumors 
arising from lymphoreticular cells 
traditionally have been grouped under a 
heading of reticulosis or histiocytic lymphoma. 
• Skull tumors that affect the brain by local 
extension include osteosarcoma, chondro -
sarcoma, and multilobular osteochondro -
sarcoma. • The most frequently seen 
secondary tumors of dogs include local 
extension of nasal adenocarcinoma; 
metastases from mammary, prostatic, or 
pulmonary adenocarcinoma; metastases from 
hemangiosarcoma; and extension of pituitary 
adenoma or carcinoma. • Nerve sheath 
tumors arising from cranial nerves 
(particularly oculomotor nerve and 
trigeminal nerve) may occur in dogs.
Cats
• Meningiomas involving multiple 
intracranial sites (including third ventricle) 
relatively common in cats. • Primary brain 
tumors other than meningiomas occur 
infrequently in cats. • T umors that have been 
reported include astrocytoma, ependymoma, 
oligodendroglioma, choroid plexus papilloma, 
medulloblastoma, lymphoma, olfactory 
neuroblastoma, and gangliocytoma. 
• Lymphoma of the brain may be primary or 
secondary, or may be an aspect of multicentric 
lymphoma of cats. • Secondary tumors that 
have been reported to occur in the brain of 
cats include pituitary macroadenomas and 
macrocarcinomas, and metastatic carcinoma. 
• Local extension may occur either from 
tumors of middle ear cavity (e.g., squamous 
cell carcinoma), nasal cavity (e.g., nasal 
adenocarcinoma), or skull (e.g., 
osteosarcoma).
  TREATMENT
• Beyond general efforts to maintain homeo  - 
stasis, major goals of therapy for brain tumor 
are to control secondary effects, such as 
increased ICP or cerebral edema, and to 
eradicate the tumor or reduce its size. 
• Beyond palliative care, three methods of 
therapy for a brain tumor currently are available for use in dogs and cats: surgery, 
irradiation, and chemotherapy.
Surgery
• Neurosurgical intervention is an essential 
consideration in management of brain tumors 
in cats or dogs, whether for complete excision, 
partial removal, or biopsy. • Meningiomas, 
particularly those located over cerebral 
convexities or in frontal lobes of cerebrum, 
may be completely (or almost completely) 
removed by surgery, especially in cats. 
• Primary calvarial tumors also may be 
removed surgically prior to other types of 
therapy.
Radiation Therapy
• Irradiation may be used either alone or in 
combination with other treatments for either 
primary or secondary brain tumors. • Careful 
treatment planning by qualified and 
experienced radiation therapist is essential to 
success of radiation therapy. • A major 
development in radiation therapy is 
emergence of more precise protocols that 
spare tissues surrounding the brain tumor 
(e.g., stereotactic radiotherapy).
Chemotherapy
Alkylating agents (e.g., carmustine [BCNU], 
lomustine [CCNU], and temozolomide), 
antimetabolic agents (e.g., cytosine arabino-
side), and ribonucleotide reductase inhibitors 
(e.g., hydroxuurea) may result in reduction of 
tumor size and improvement of clinical signs 
in dogs with glial cell tumors; however, 
evidence of efficacy in animals is lacking.
• Glucocorticoids may be used for edema 
reduction and, in some cases (e.g., lymphoma), 
for retardation of tumor growth. • Some 
animals with brain tumor demonstrate 
dramatic improvement in clinical signs for 
weeks or months with sustained gluco -
corticoid therapy. • Antiepileptic drugs (e.g., 
phenobarbital, bromide, levetiracetam) may 
be utilized for control of generalized seizures. 
• Mannitol and hypertonic saline are agents 
best suited for effective reduction of increased 
ICP .
  FOLLOW-UP
• Serial neurologic examinations. • Serial CT 
or MRI examinations.POSSIBLE COMPLICATIONS
• Aspiration pneumonia due to depressed 
swallowing reflexes associated with increased 
ICP . • Seizures.
• Little information available concerning 
survival times of dogs or cats with brain 
tumor that have received only palliative 
therapy (i.e., therapy to control secondary 
effects of a tumor without an attempt to 
eradicate the tumor). • Results of one study 
indicate mean and median survival of 81 days 
and 56 days, respectively, following CT 
diagnosis of primary brain tumor in each of 8 
dogs. • Results from several studies confirm 
that prognosis for a dog or cat with a primary 
brain tumor may be significantly improved by 
surgical removal and irradiation, either alone 
or in combination.
Dogs that have been treated for a brain tumor 
may develop a second type of tumor 
elsewhere in the body.
• CSF = cerebrospinal fluid. 
• ICP = intracranial pressure. 
• PNET = primitive neuroectodermal tumor.
Dickinson PJ. Advances in diagnostic and 
treatment modalities for intracranial 
tumors. J Vet Intern Med 2014, 
28:1165–1185.
Dickinson PJ. Intracranial tumors in dogs. 
Vet Focus 2014, 24(2):2–10.
Hicks J, Platt S, Kent M, Haley A. 
Canine brain tumors: a model for 
human disease? Vet Comp Oncol 2017, 
15(1):252–272.
Kohler RJ, Arnold SA, Eck DJ, et al. 
Incidence of and risk factors for major 
complications or death in dogs undergoing 
cytoreductive surgery for treatment of 
suspected primary intracranial masses. 
J Am Vet Med Assoc 2018, 
253(12):1594–1603.
Rossmeisl JH. New treatment modalities for 
brain tumors in dogs and cats. Vet Clin 
Small Anim 2014, 44:1013–1038.
Author  Richard A. LeCouteur
available online(continued)  Brain Tumors

B196  Blackwell’s Five-Minute Veterinary Consult  
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  BASICS
Timing of insemination(s) to maximize 
pregnancy risk and litter size.
Dogs
• Must determine ovulation day so that 
breeding(s) occur(s) at proper time. • Fresh, 
chilled, or frozen semen—usually limited to 
one or two inseminations; insemination must 
be timed relative to ovulation for maximum 
fertility. • Ovulation may vary relative to 
onset of heat (proestrus), standing heat 
(estrus), vaginal cytology. • Luteinizing 
hormone (LH)—controls ovulation; peaks on 
same day or after full cornification is 
observed; ovulation occurs approximately 2 
days after peak; 2–3 days (54–72 hours) more 
required for oocyte maturation; mature 
oocytes viable for minimum 2–3 days; thus 
fertile period is 4–8 days after LH peak, and 
maximum fertility is 5–6 days after LH peak. 
• Serum progesterone concentration—
increase closely associated with LH peak.
Cats
• Ovulation—usually induced; timing of 
breeding is not as critical as with dogs; depends 
on adequate gonadotropin-releasing hormone 
(GnRH) and then LH release triggered by 
vaginal stimulation. • Adequate stimulation—
characterized by copulatory cry and postcoital 
reaction; frequency of coital stimuli important 
in determining adequacy of coital contact. 
• LH—peak concentration and duration of 
elevation determine number of follicles 
ovulating; higher concentration with multiple 
copulations; response to copulation depends 
on day of estrus (greater release on estrus day 3 
than on estrus day 1); release partially depends 
on duration of exposure to estrogen.
Reproductive
GENETICS
N/A
N/A
N/A
SIGNS
Dogs
• Onset of estrus—usually associated with a 
change in the vaginal discharge from 
sanguineous to barely red and decreased 
vulvar edema; sanguineous discharge may continue during estrus and cease only at the 
onset of diestrus. • Physical signs alone—
unreliable for precise determination of fertile 
period. • Receptivity—may be detected by 
touching the perineum near the vulva; if 
receptive, female will “flag” by elevating the 
tail to one side and lifting the vulva dorsally.
Cats
LH response to a single mating—may vary 
substantially.
Dogs
Sanguineous vulvar discharge during estrus.
Cats
Return to estrus in <30 days may indicate 
failure to ovulate; interestrus usually 8–10 
days, but highly variable even within queen; 
some queens will breed while pregnant.
Dogs
• Interest shown by male. • Vulva less turgid.
• Vaginal discharge—less color and amount.
• Flagging. • Females show mounting 
behavior. • Fully cornified and crenulated 
pale vaginal epithelium. • Digital palpation 
of vagina may be resented by bitch in 
proestrus, improving throughout proestrus 
until estrus. May feel edematous mass on 
floor of caudal vagina, just cranial to urethral 
os, that should shrink as optimal breeding 
period approaches.
Cats
• Fully cornified vaginal epithelium. 
• Interest shown by male. • No changes in 
external genitalia. • Vocalizes, rubs objects. 
• Lordosis.
CAUSES
Dogs
• Limited number of breedings. • Female 
unreceptive to male. • Artificial insemination 
(fresh, chilled, or frozen semen).
Cats
• Coitus—too early or too late in estrus; too 
few times. • Artificial insemination.
N/A
  DIAGNOSIS
• Vaginal discharge—proestrus or estrus; 
vaginitis; neoplasia, pyometra, urinary tract 
infection. • Refusal to allow intromission—
anatomic abnormalities of Mullerian duct 
development, vulvovestibular or vestibulo -
vaginal junction, acquired abnormality from 
dystocia or breeding trauma, vaginal 
hyperplasia, behavioral.CBC/BIOCHEMISTRY/URINALYSIS
N/A
Dogs
• Semi-quantitative progesterone ELISA—
adjunct to vaginal cytologic examination. 
• Quantitative serum progesterone testing—
preferred when breeding with frozen semen; 
especially useful in animals with reduced 
fertility. Commercial labs or in-house 
machines available. ◦ Progesterone 
concentration <1 ng/mL (3.18 nmol/L) 
before LH peak, 1.5–4 ng/mL (4.8–
12.7 nmol/L) at LH peak, 4–10 ng/mL 
(12.7–31.8 nmol/L) at ovulation; continues 
to rise during diestrus/pregnancy. 
◦ Commercial laboratories use various 
methods of progesterone concentration 
measurement, so values indicative of LH and 
ovulation vary among labs. ◦ Documenting 
rapid rise in progesterone concentration 
subsequent to initial rise is more reliable 
indicator of ovulation than single measure -
ment of LH peak or initial rise in 
progesterone. • LH testing—must sample 
daily to observe LH peak; can use serum 
progesterone to signal when to start testing or 
use the initial rise in progesterone concentration 
as surrogate for LH peak.
Cats
Serum progesterone testing to verify 
ovulation.
IMAGING
Ultrasonographic imaging of ovaries—may 
help determine ovulation; perform daily, best 
if using color flow Doppler.
Dogs
• Vaginal cytologic examination—imprecise 
indicator of fertile period; cornification of 
vaginal epithelium with clear background 
usually coincides with sexual receptivity. 
◦ Proestrus (in breeder terms, “day 1,” first 
sign of hemorrhagic vaginal discharge)—most 
epithelial cells are noncornified. ◦ Percentage 
of cornified cells (cells with angular cytoplasm 
and pyknotic nuclei or nuclei that fail to take 
up stain) increases during proestrus. 
◦ Estrus—90% or more cornified cells, 
background of slide free of debris. ◦ Breeders 
refer to estrus by day, usually occurs day 
10–18 in breeder terms. ◦ Diestrus—abrupt 
decline in percentage of cornified cells (20–50%) 
in a single day: day 1 of diestrus (D1); normal 
to see neutrophils on days 1–4 of diestrus. 
• Vaginoscopy—edematous vaginal folds 
until LH peak, then vagina pale with slight 
wrinkling (crenulation) as edema decreases 
with estradiol decline; by optimum breeding 
period crenulation is obvious, until diestrus 
when folds are flat and edema disappears.Breeding, Timing

Canine and Feline, Seventh Edition  197
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B
  TREATMENT
Dogs
• Fresh semen, multiple breedings—
inseminate q48h, starting 48–96h after 
initial rise in serum progesterone concen -
tration is observed until D1. • Fresh 
semen, two breedings—inseminate either 
on days 3 and 5 or on days 4 and 6 after 
LH peak or initial rise in serum progesterone 
concentration; use standard artificial 
insemination (AI) pipettes or modified 
Foley catheters (several sizes available); 
vaginal insemination on or after day 5 may 
be associated with reduced pregnancy rates 
and litter sizes due to beginning of cervical 
closure. • Frozen or chilled semen—frozen 
semen is less viable than chilled, thus 
timing is more critical; one or two 
intrauterine inseminations most common: 
inseminate on day 5 or 6 after LH peak or 
initial rise in serum progesterone 
concentration (day 0) or 3 days after serum 
progesterone concentration ≥5 ng/mL 
(16 nmol/L); for intrauterine insemination 
via transcervical endoscopy (TCI) or 
surgical insemination, serum progesterone 
concentration on day of insemination 
should be ≥12 ng/mL (38 nmol/L; value is 
laboratory dependent). • Timing 
insemination based on serum progesterone 
concentration improves chance of 
conception and increased litter size. 
• Blood collection and vaginal examination 
q48h are adequate in most cases.
Cats
• Increase likelihood of ovulation and litter 
size by maximizing number of matings; breed 
on successive days. • Breed at least 4 times 
daily at least 2–3 hours apart on days 2 and 3 
of estrus to maximize LH release. • May 
induce ovulation by administration of 
exogenous hormones—GnRH or human 
chorionic gonadotropin (hCG) after mating.
ACTIVITY
• No alteration in activity necessary except 
confinement—bitch will search for male. 
• Keep strictly away from unintended 
sexually intact males.CLIENT EDUCATION
Client education on physical, behavioral, and 
endocrinologic changes that occur during 
estrous cycle, and how variable timing of these 
changes can be from animal to animal, can 
improve owner compliance and satisfaction.
Surgical AI requires standard postoperative 
care.
Cats—hCG (100–500 IU/cat IM); GnRH 
(25–50  μg/cat IM).
  FOLLOW-UP
• Dogs—serial vaginal cytology to determine 
D1; ovulation is ~6 days before D1. • Dogs—
whelping is 65 ± 1 days from LH peak, 63 ± 1 
days from ovulation, or 57 ± 1 days from D1; 
for fresh, chilled, or frozen semen: repeat 
quantitative serum progesterone measurement 
after initial progesterone rise or LH peak to 
verify >10 ng/mL (32 nmol/L). • Cats—use 
serum progesterone assay 1 week post 
insemination to verify ovulation. • Cats—
queening is 62–71 days from first breeding.
N/A
Dogs
• Vaginal cytologic examinations—compare 
D1 with prospective estimation based on 
progesterone; if estimates differ, pregnancy 
rates are reduced. • Semi-quantitative 
progesterone kits—must come to room 
temperature before use; concentrations falsely 
elevated when using a cold kit. • Serum 
progesterone concentration—allow blood to 
clot at room temperature; separate cells from 
serum 20 minutes after collection; falsely low 
concentrations occur when using serum mixed 
with red blood cells (progesterone binds to 
erythrocytes). • Hemolyzed or lipemic 
specimen—may give falsely low progesterone 
concentration. • Quantitative (chemiluminescence assay, fluorescence, 
ELISA) progesterone assay—more accurate 
than semi-quantitative kits; several in-house 
analyzers available; turnaround times should 
be less than 24 hours. • Serum separator tubes 
cause false elevations in chemiluminescence 
progesterone assay; anticoagulant may affect 
reported concentration (serum > heparin 
plasma > EDTA plasma).
Split heats in young bitches—period of 
proestrus (may be prolonged to 6 weeks or 
more), followed by cessation of signs, and 
subsequent resumption of estrus cycle (1–3 
weeks later); no initial rise in progesterone or 
LH concentration occurs with first proestrus/
estrus; subsequent estrus usually normal.
Ultrasound—conceptuses can first be 
detected 18–20 days after LH peak (requires 
high-resolution, high-frequency probe, easier 
in toy breeds) or 2–3 days earlier in cats; 
commonly done 4 weeks post breeding; 
recommend earlier exam in bitches with 
history of pregnancy loss or infertility.
SEE ALSO
• Ovulatory Failure.
• Vaginal Discharge.
• Vaginal Malformations and Acquired Lesions.
• AI = artificial insemination.
• D1 = first day of diestrus.
• hCG = human chorionic gonadotropin.
• TCI = endoscopic transcervical insemination.
Johnston SD, Root Kustritz MV, Olson PN. 
Breeding management, artificial insemina-
tion, in vitro fertilization, and embryo 
transfer in the queen. In: Johnston SD, 
Root Kustritz MV, Olson-Schultz P , eds., 
Canine and Feline Theriogenology. 
Philadelphia, PA: Saunders, 2001, pp. 
406–413.
Author  Cathy J. Gartley
Consulting Editor  Erin E. Runcan(continued)  Breeding, Timing

B
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  BASICS
OVERVIEW
• Clinical condition seen primarily in dogs; 
irreversible dilatation of the bronchi; caused 
by chronic infectious or inflammatory airway 
disease, foreign body pneumonia, or 
associated with primary ciliary dyskinesia.
• Occurs in cats as a sequela to longstanding 
inflammatory lung disease or neoplasia.
• Airways are pulled open by surrounding 
lung tissue; pooling of secretions can occur, 
which perpetuates lung damage and allows 
colonization by bacteria.
• Can be cylindrical or saccular, focal or 
diffuse.
• Primarily dogs but radiographically 
detected in many cats.
• Cocker spaniels and perhaps West 
Highland white terriers predisposed.
• Young animals ( <1 year) with primary 
ciliary dyskinesia.
• Middle-aged to old dogs with chronic 
pulmonary disease.
SIGNS
• Chronic cough—usually moist and 
productive; hemoptysis.
• Recurrent fever.
• Tachypnea or respiratory distress.
• Chronic nasal discharge or sinusitis, 
particularly with primary ciliary dyskinesia.
• Moist, harsh inspiratory crackles; loud 
expiratory lung sounds or wheezes on 
physical exam.
• T racheal hypersensitivity.
• Primary ciliary dyskinesia.
• Inadequately treated infectious or 
inflammatory lung conditions (pneumonia, 
bronchitis, or eosinophilic lung disease).
• Smoke inhalation, chronic aspiration 
pneumonia, radiation injury, and inhalation 
of environmental toxins—predispose animal 
to airway injury and colonization by bacteria.
• Chronic bronchial obstruction or foreign 
body pneumonia—development of bronchiec -
tasis distal to the obstructed region common.
• Signs related to bronchiectasis may not be 
recognized until long after the primary injury.
  DIAGNOSIS
• Recurrent bacterial bronchopneumonia.
• Fungal pneumonia.
• Chronic bronchitis.
• Infectious or parasitic bronchitis.• Foreign body pneumonia.
• Neutrophilia and monocytosis.
• Proteinuria—can be seen with secondary 
amyloidosis, glomerulonephritis, or sepsis.
Arterial blood gas analysis—hypoxemia; 
widened alveolar–arterial oxygen gradient.
IMAGING
• Radiography—insensitive for the diagnosis. 
Abnormalities visible late in the course of 
disease include dilatation of the lobar bronchi 
with lack of normal tapering in the periphery; 
diffuse thickening of bronchial walls; mixed 
bronchial, interstitial, and alveolar pattern.
• Changes can be focal or diffuse.
• CT—bronchus >2 times the width of the 
adjacent pulmonary artery in dogs, 
abnormally dilated bronchi near the lung 
periphery; thickened airways; cystic 
dilatations of the bronchi with or without 
pulmonaray consolidation.
• Bronchoscopy—saccular or tubular 
dilatation of the airways.
• Airway sampling—cytologic examination 
of bronchoalveolar lavage fluid or tracheal 
wash specimens; culture for aerobic and 
anaerobic bacteria and Mycoplasma ; typically 
find suppurative inflammation with high 
numbers of neutrophils, or increased 
eosinophils indicating eosinophilic broncho -
pneumopathy; may culture a mixed 
population of bacteria; some cases appear to 
have sterile inflammation.
• Dilated bronchi.
• Diffuse peribronchial and alveolar 
inflammation and fibrosis.
• Squamous metaplasia of bronchial 
epithelium.
  TREATMENT
• Inpatient—severe condition: intravenous 
fluids and antibiotics; oxygen administration.
• Airway nebulization and coupage to 
facilitate removal of viscid pulmonary 
secretions, often lifelong.
• Gentle activity enhances clearance of 
secretions.
• Long-term antibiotic administration.
• Stress to owner the importance of 
appropriate follow-up care.
• Single affected lung lobe or bronchial 
obstruction—lung lobectomy can be 
curative.  MEDICATIONS
• Intravenous antibiotics—may be required 
initially; good choices: ampicillin (10–20 mg/
kg IV q6–8h) and enrofloxacin (5–10 mg/kg 
q24h).
• Broad-spectrum agents with efficacy against 
both aerobes and anaerobes and that offer 
good penetration of pulmonary tissue—
preferred; combination of enrofloxacin 
(5–20 mg/kg PO q24h) and clindamycin 
(5–11 mg/kg PO q12h) or amoxicillin–
clavulanate often effective.
• Azithromycin can be a good alternative 
antibiotic for outpatient care.
• Long-term use of antibiotics (2 months to 
lifelong)—based on bacterial culture and 
sensitivity testing; may be required even if 
culture of airway specimens yields no growth.
• Bronchodilators—may be beneficial, 
although animals usually have irreversible 
airflow limitation; extended release theophylline 
advised.
• Eosinophilic lung disease requires treatment 
with glucocorticoids.
• Saline nebulization and coupage highly 
beneficial in removing secretions.
• Theophylline derivatives and fluoro -
quinolones—concurrent use causes high and 
possibly toxic plasma theophylline 
• Furosemide—avoid; dries airway secretions.
• Cough suppressants—avoid; will trap 
secretions and bacteria in lower airway and 
perpetuate damage.
  FOLLOW-UP
• Clinical response—outpatient.
• Serial CBC, blood gas analysis, and thoracic 
• Antibiotics—complete a full course of 
therapy in patients that appear to have 
parenchymal involvement.
• Early recognition and resolution of foreign 
body pneumonia.
• Appropriate treatment of eosinophilic 
pneumonia.
Chronic recurrent pulmonary infection likely.
• Chronic and recurrent clinical signs 
expected; some degree of coughing will always 
be present.Bronchiectasis

Canine and Feline, Seventh Edition  199
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• Animals can live for years with bronchiec -
tasis if managed properly.
• Some patients succumb to respiratory 
failure.
• Other organs may fail if bacteremia or 
glomerulonephritis develops.
• Chronic sinusitis.• Chronic bronchitis.
• Pneumonia—bacterial, eosinophilic 
aspiration, foreign body.
• Smoke inhalation.
Cannon MS, Johnson LR, Pesavento PA, 
et al. Quantitative and qualitative computed 
tomographic imaging features of 
bronchiectasis in dogs. Vet Rad US 2013, 
54(4):351–357.
Hawkins EC, Basseches J, Berry CR, et al. 
Demographic, clinical, and radiographic 
features of bronchiectasis in dogs: 316 cases (1988–2000). J Am Vet Med Assoc 2003, 
223(11):1628–1635.
Johnson LR, Johnson EG, Vernau W, et al. 
Bronchoscopy, imaging, and concurrent 
diseases in dogs with bronchiectasis 
(2003–2014). J Vet Int Med 2016, 
30(1):247–254.
Author  Lynelle R. Johnson
Consulting Editor  Elizabeth Rozanski(continued)  Bronchiectasis

B200  Blackwell’s Five-Minute Veterinary Consult  
B
  BASICS
• Chronic coughing for longer than 2 months 
that is not attributable to another cause (e.g., 
neoplasia, congestive heart failure, 
eosinophilic pneumonia, or infectious 
bronchitis). • Partly nonreversible and often 
slowly progressive condition owing to 
accompanying pathologic airway changes.
• Recurrent airway inflammation suspected, 
but a specific cause is rarely determined. 
• Persistent tracheobronchial irritation—
causes chronic coughing; leads to changes in 
tracheobronchial epithelium and submucosa. 
• Airway inflammation, epithelial edema, and 
thickening—prominent. • Excess production 
of thickened mucus is a hallmark. • In severe, 
very chronic cases—probable increased lung 
resistance; decreased expiratory airflow, 
especially in cats; in dogs, possible sequelae 
such as broncholamacia and bronchiectasis.
• Respiratory • Cardiovascular—pulmonary 
hypertension, cor pulmonale. • Nervous— 
syncope (infrequent).
Common in dogs and cats.
Worldwide
Species
• Dogs—small and toy breeds common; also 
observed in large breeds. • Siamese cats and 
domestic shorthairs affected.
Most often affects middle-aged and old 
animals.
N/A, although spayed females are often 
overrepresented (might be due to weight 
gain).
SIGNS
• Coughing—hallmark of tracheobronchial 
irritation; usually harsh and dry; post-tussive 
gagging common (owners often misinterpret 
this as vomiting, especially in dogs). 
• Exercise intolerance, difficult breathing, 
wheezing (in cats). • Cyanosis and even 
syncope may be noted in severe cases.
• Patients usually bright, alert, and afebrile. 
• T racheal palpation—typically results in coughing because of increased tracheal 
sensitivity. • Small airway disease—assumed 
when expiratory abdominal push (during 
quiet breathing) or end-expiratory wheezing is 
detected. • Bronchovesicular lung sounds, 
end-inspiratory crackles, and wheezing (result 
of airflow into obstructed airways) may be 
heard. • Loud end-expiratory snap is 
suggestive of concurrent airway collapse. 
• Cardiac auscultation—murmurs secondary 
to valvular insufficiency common in dogs, but 
not always associated with congestive heart 
failure; chronic bronchitis usually results in 
normal or slower than normal resting heart 
rate and pronounced sinus arrhythmia; in cats, 
tachycardia is possible. • Obesity— common; 
important complicating factor. • Severe dental 
disease may predispose to lower airway colon  - 
ization and possible infection (dogs).
CAUSES
Chronic airway inflammation initiated by 
multiple causes, although specific cause rarely 
identified.
• Long-term exposure to inhaled irritants. 
• Obesity. • Recurrent bacterial infection. 
• Dental disease and laryngeal disease—result 
in bacterial showering of lower airways.
  DIAGNOSIS
• Bronchiectasis. • Eosinophilic broncho -
pneumopathy. • Foreign bodies. • Heartworm 
disease. • Bacterial, pneumonia. • Neoplasia—  
metastatic more than primary. • Pulmonary 
parasites or parasitic larval migration. 
• Pulmonary fibrosis—cats and dogs. 
• Pulmonary granulomatosis. • Congestive 
heart failure—typically associated with high 
resting heart rate and left atrial enlargement, 
which may lead to collapse of left principal 
bronchus.
• Rarely diagnostic. • Neutrophilic 
leukocytosis common. • Absolute eosinophilia—  
suggests but not diagnostic for allergic 
bronchitis. • Polycythemia secondary to 
chronic hypoxia—may be seen. • Liver 
enzymes and bile acids may be elevated due 
to passive congestion.
• Fecal and heartworm tests—rule out 
pulmonary parasites. • Pulse oximetry—
useful for detecting hemoglobin desaturation. 
• Arterial blood gas analysis—collect, ice, 
and have analyzed at a local hospital; mild to 
moderately low partial pressure of oxygen 
(PaO2) seen with severe condition; aids in 
prognosis and monitoring treatment. • As hyperadrenocorticism could be responsible 
for obesity and/or enlarged liver/abdomen, 
testing should be considered if clinically 
IMAGING
Thoracic Radiography (High Resolution 
Computed Topography)
Common features (in descending order of 
frequency)—bronchial thickening; interstitial 
pattern; middle lung lobe consolidation 
(cats); atelectasis; hyperinflation and 
diaphragmatic flattening (primarily cats).
• May reveal right heart enlargement with 
pulmonary hypertension. • Helps rule out 
cardiac disease as a cause of coughing. 
• Check for pulmonary hypertension via 
Doppler echocardiography.
Preferred test for assessing the lower airways. 
• Allows direct visualization of structural as 
well as functional (dynamic) changes; allows 
selected airway sampling (e.g., biopsy and 
lavage). • Gross changes—excess mucoid to 
mucopurulent secretions; epithelial edema or 
thickening with blunting of bronchial 
bifurcations; irregular or granular mucosa; 
mucosal polypoid proliferations can indicate 
chronic bronchitis or chronic eosinophilic 
pneumonia. • Large airway caliber changes 
(e.g., static or dynamic airway collapse and 
bronchiectasis)—may be detected as 
complicating problems.
Evaluation of Airway Secretions
• Must collect from lower airways—helps to 
establish underlying cause if present or to 
determine the severity of inflammation. 
• Throat swab cultures are not representative 
of lower airway flora • T racheal aspiration or 
bronchoalveolar lavage—collect specimens for 
cytologic examination and bacterial/
mycoplasmal culture or qPRC assessment. 
• Quantitated aerobic bronchoalveolar lavage 
(BAL) cultures help differentiate infection 
versus airway colonization; reported cutoff is 
>1.7 × 103 colony-forming units (CFU) for 
infection in dogs. Anaerobic and Mycoplasma  
cultures recommended as well. • Cytology—
inflammation primary finding; most cells are 
neutrophils, eosinophils, or macrophages; 
evaluate for bacteria, parasites, neoplastic cells, 
and contamination with foreign material. 
• Recurrent infections—implicated in patho  - 
genesis of bronchitis; however, positive cultures 
are not frequently reported; Mycoplasma  infection 
discussed but rarely confirmed as a cause.
See Bronchoscopy under Diagnostic 
Procedures.Bronchitis, Chronic

Canine and Feline, Seventh Edition  201
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  TREATMENT
• Usually outpatient—oxygen can be given at 
home in chronic cases. • Inpatient—if 
requires oxygen therapy, parenteral medication, 
or aerosol therapy; patients that owners 
cannot keep calm at home during initial 
stages of therapy.
Consider saline nebulization followed by 
coupage and/or gentle exercise to encourage 
removal of airway secretions.
ACTIVITY
• Exercise—moderate (not forced) useful in 
clearing secretions; assists with weight loss. 
• Limit if exertion causes excessive coughing. 
• Use a harness instead of a collar.
DIET
Weight loss critical—improves PaO2, attitude, 
and exercise tolerance in obese patients; 
reduces cough frequency.
• Warn client that chronic bronchitis is an 
incurable disease and complete suppression of 
all coughing is an unattainable goal. • Stress 
that aggressive treatment (including weight 
control, avoiding risk factors, and medical 
treatment) minimizes the severity of the 
coughing and slows disease progression in 
most patients.
T reat severe dental disease to minimize 
secondary bacterial complications.
• Diminish airway inflammation and 
coughing regardless of the underlying cause. 
• Indicated for noninfectious conditions. 
• With allergic or hypersensitivity reactions—
require long-term administration; attempt to 
wean off steroids or determine lowest effective 
dosage. • Prednisolone preferred in cats. 
• Prednisone or prednisolone usually initiated 
at 0.5–1 mg/kg PO q12h for a variable time, 
with tapering of the dosage based on clinical 
signs. • Inhaled agents (e.g., budenoside or 
fluticasone 1–3 puffs using metered dose 
inhalers [variable concentrations exist] a day) 
are often effective and can be used to reduce 
systemic side effects of corticosteroids; they 
are delivered via a spacer chamber and face mask (e.g., AeroDawg); however, the most 
adequate dose is not clearly established.
Commonly prescribed, although limited 
evidence of efficacy.
• Select on basis of quantitated culture and 
sensitivity test results.
Antitussives
• Indicated for nonproductive, paroxysmal, 
continuous, or debilitating cough. • Dogs—
butorphanol (0.55 mg/kg PO q6–12h; 
0.055–0.11 mg/kg SC); hydrocodone 
(0.1–0.3 mg/kg q6–8h PO). Over-the-
counter cough suppressants are rarely 
effective; gabapentin 2–5mg.kg by mouth 
every eight hours (but unestablished efficacy).
Lasix and atropine—do not use because 
of drying effects on tracheobronchial 
• Beta agonists (e.g., terbutaline and 
albuterol)—may cause tachycardia, 
nervousness, and muscle tremors; typically 
transient. • Theophylline—may cause 
tachycardia, restlessness, excitability, 
vomiting, and diarrhea; evaluate ethylene 
diamine tetra-acetate (EDTA) plasma sample 
for peak plasma concentration (ideally 
5–20  μg/mL); toxicity may be more common 
with generic formulations.
Fluoroquinolones decrease theophylline 
clearance in dogs and can result in 
theophylline toxicity.
Maropitant (some antitussive properties 
suggested, but not advised yet).
  FOLLOW-UP
• Follow abnormalities revealed by physical 
examination and selected diagnostic tests— 
determine response to treatment. • Monitor 
weight; arterial blood gases usually improve 
after significant weight loss.
Avoid and address risk factors (see Risk 
Factors).
• Syncope—possible complication of 
chronic coughing, particularly in toy-
breed dogs. • Pulmonary hypertension 
and cor pulmonale—most serious complications. • Bronchectasis and airway 
remodeling.
• Progressive airway changes—syncopal 
episodes, chronic hypoxia, right ventricular 
hypertrophy, and pulmonary hypertension. 
• Acute exacerbations—common with 
seasonal changes, air quality changes, 
worsened inflammation, and potentially 
development of secondary infection.
• Syncope—secondary to chronic coughing 
or development of pulmonary hypertension. 
• Increased susceptibility to airway infection, 
chronic hypoxia, pulmonary hypertension, 
and cor pulmonale.
Safety in pregnant animals not established for 
most of the recommended drugs.
SYNONYMS
Chronic bronchitis.
SEE ALSO
• Asthma, Bronchitis—Cats. • Bronchiectasis. 
• Cough. • Hypoxemia. • T racheal Collapse.
• BAL = bronchoalveolar lavage. • CFU = 
colony-forming unit. • EDTA = ethylene 
diamine tetra-acetate. • PaO2 = partial 
pressure of oxygen.
Grotheer M, Hirschberger J, Hartmann K, et 
al., Comparison of signalment, clinical, 
laboratory and radiographic parameters in 
cats with feline asthma and chronic bronchi -
tis. J Feline Med Surg. 2020, 22(7):649–655.
Reinero CR, Masseau I, Grobman M, et al., 
Perspectives in veterinary medicine: 
Description and classification of bronchi-
olar disorders in cats. J Vet Intern Med. 
2019, 33(3):1201–1221.
Rozanski E. Canine chronic bronchitis. An 
update . Vet Clin N Am Small Anim Pract 
2020, 50:393–404.
Author  Cécile Clercx
available online(continued)  Bronchitis, Chronic

B
202  Blackwell’s Five-Minute Veterinary Consult  
B
  BASICS
• Contagious disease of dogs caused by 
Brucella canis . • Rarely caused by B. suis , B. 
abortus , or B. mellitensis . • Characterized by 
abortion and infertility in females, epididymitis 
and testicular atrophy in males.
B. canis —a small, intracellular Gram-negative 
bacterium; has propensity for growth in 
lymphatic, placental, and male genital 
(epididymis and prostate) tissues.
• Hemic/lymph/immune—lymph nodes, 
spleen, bone marrow, mononuclear leukocytes. 
• Reproductive—target tissues of gonadal 
steroids (gravid uterus, fetus, testes 
epididymides, prostate gland). • Other 
tissues—intervertebral discs, anterior uvea, 
meninges (uncommon).
GENETICS
No known genetic predisposition.
• Incidence unknown. • Seroprevalence—not 
well defined; false-positive results common 
with agglutination tests. • Prevalence— 
1–18% in United States, Japan; higher in 
rural United States; 25–30% in stray dogs in 
Mexico, Peru.
United States, Mexico, Japan, South America; 
Spain, T unisia, China, Bulgaria; individual 
outbreaks in Germany, Czech Republic.
Species
Dogs
• No evidence of breed susceptibility, 
reportedly high prevalence in beagles. • Pure 
breeds in commercial kennels (“puppy mills”).
• Any age. • Most common in sexually 
mature dogs.
Most common in females.
SIGNS
Suspect with abortions, reproductive failures, 
or genital disease.
• Animals may appear healthy or have vague 
signs of illness. • Lethargy. • Loss of libido. 
• Swollen lymph nodes. • Back or neck pain. 
• Abortion—commonly 6–8 weeks after 
conception, although pregnancy may 
terminate at any stage.Physical Examination Findings
• Peripheral lymphadenopathy. • Males—
swollen scrotum with scrotal dermatitis, 
enlarged firm epididymides, orchitis, 
prostatitis. • Chronic infection—unilateral or 
bilateral testicular atrophy, spinal pain, 
discospondylitis, posterior weakness, ataxia. 
• Chronic recurrent anterior uveitis without 
signs of systemic disease; also iris hyperpig -
mentation, vitreal infiltrates, multifocal 
chorioretinitis. • Vaginal discharge—may last 
several weeks after abortion. • Fever (rare).
CAUSES
B. canis —Gram-negative coccobacillus; 
morphologically indistinguishable from other 
members of genus.
• Breeding kennels, pack hounds. • Contact 
with strays in endemic areas.
  DIAGNOSIS
• Abortions—maternal, fetal, or placental 
abnormalities. • Systemic infections—canine 
distemper, canine herpesvirus, B. abortus , 
hemolytic streptococci, E. coli , leptospirosis, 
toxoplasmosis. • Inguinal hernia. 
• Discospondylitis—fungal infections, 
actinomycosis, staphylococcal infections, 
nocardiosis, streptococci, or Corynebacterium 
diphtheroids.
• Normal in uncomplicated cases. • Chronic 
infection—hyperglobulinemia and hypo -
albuminemia. • Cerebrospinal fluid—
neutrophilic pleocytosis, elevated protein 
(meningoencephalitis); normal in 
discospondylitis. • Urinalysis usually 
normal.
Serologic testing—most common diagnostic 
method; subject to error due to false-positive 
reactions to several species of bacteria 
common with tube agglutination tests; 
chronically infected dogs may test negative.
Rapid 2-Mercaptoethanol Slide 
Agglutination Test (RSAT)
• Simple, inexpensive, rapid. • Detects 
infected dogs 3–4 weeks after infection; 
accurate in identifying noninfected dogs. 
• Screening test—sensitive, not specific; high 
rate (50%) of false-positive tests. • Confirm 
results with other tests.
Mercaptoethanol Tube Agglutination 
Test (2ME)
• Semi-quantitative—similar information to 
RSAT, but inactivates immunoglobulin (Ig) M. 
• Good screening test (lacks specificity). • If positive RSAT and negative 2ME, retest in 
2–4 weeks.
Agar Gel Immunodiffusion (AGID) Test
• Soluble antigen test—recommended; 
employs antigens highly specific for 
antibodies against Brucella  spp. (including B. 
canis, B. abortus , and B. suis ); reactive 
antibodies appear 4–12 weeks after infection 
and persist; may be positive after other tests 
become equivocal or negative.
• ELISA—using purified cytoplasmic 
antigens; not yet commercially available. 
• PCR—available at some diagnostic 
laboratories; high sensitivity and specificity. 
• Cell wall antigen test—not recommended; 
highly sensitive but not standardized; frequent 
false positives.
IMAGING
Discospondylitis—radiographic changes slow 
to develop, may not be seen even when spinal 
pain is present.
Isolation of Organism
• Blood cultures—when clinical and serologic 
findings suggest diagnosis, can be isolated 
from blood of infected dogs if they have not 
received antibiotics; onset of bacteremia 2–4 
weeks after oral-nasal exposure, persists for 8 
months to 5.5 years. Culture is preferred 
method for diagnosis in endemic situations or 
with known exposure (1–8 weeks ago); must 
specifically request Brucella  culture. • Culture 
or PCR of vaginal fluids or vaginal swab after 
abortion. • Semen or urine—PCR more 
practical than culture. • Tissue samples— 
culture or PCR of prostate, testicle, epididymis, 
lochia, or placenta. • Contaminated 
samples—media that contain antibiotics (e.g., 
Thayer–Martin medium) have proven useful.
Semen Quality
• Sperm motility, immature sperm, inflamm -
atory cells (neutrophils) with epididymitis. 
• Abnormalities usually evident by 5–8 weeks 
post infection; conspicuous by 20 weeks. 
• Azoospermia without inflammatory cells 
common with bilateral testicular atrophy.
Lymph Node Biopsy
• Tissues (lymph node, uterus, testes) should 
be sterilely obtained, cultured on appropriate 
media, and submitted for histopathology. 
• Lymphoid hyperplasia—large numbers of 
plasma cells. • Intracellular bacteria—may be 
observed in macrophages with special stains 
(e.g., Brown–Brenn stain). • Histopathologic 
examination of testes—necrotizing vasculitis, 
inflammatory cells, granulomatous lesions.
• Gross findings—lymph node enlargement, 
splenomegaly, enlarged and firm epididymides, 
scrotal edema, or atrophy of one or both testes; 
chronic infection: anterior uveitis and 
discospondylitis. • Microscopic changes—Brucellosis

Canine and Feline, Seventh Edition  203
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diffuse lymphoreticular hyperplasia; chronic 
infection: lymph node sinusoids with plasma 
cells and macrophages that contain bacteria, 
diffuse lymphocytic infiltration and granulo -
matous lesions in all genitourinary organs 
(especially prostate, epididymis, uterus, and 
scrotum); inflammatory cell infiltration and 
necrosis of prostate parenchyma, seminiferous 
tubules. • Ocular changes—granulomatous 
iridocyclitis; exudative retinitis; leukocytic 
exudates in anterior chamber.
  TREATMENT
ACTIVITY
• Goal is eradication of B. canis  from animal 
(seronegative, no bacteremia for at least 3 
months); sometimes result is persistent low 
antibody titers with no systemic infection. 
• Antibiotic treatment is expensive, time 
consuming, and controversial (because 
outcomes are uncertain, and organism has 
potential to recrudesce). • Euthanasia is 
strongly recommended for breeding or 
commercial kennels; treatment is only 
recommended for spayed or castrated dogs if 
the owner is willing to accept the ongoing 
zoonotic risk. • Before treatment is attempted 
for an intact household pet or breeding dog, 
client must clearly agree that animal will be 
neutered and potentially euthanized if 
treatment fails. • Zoonotic infection is a 
possibility; discuss proper sanitation and 
prevention of exposure.
Neuter/spay plus treatment—when 
euthanasia is unacceptable to owner.
• Several therapeutic regimens have been 
evaluated, results have been equivocal; treat  - 
ment duration longer than 30 days may be 
required. • Most successful—combination of 
a tetracycline (tetracycline hydrochloride, chlortetracycline, or minocycline: 25 mg/kg 
PO q8h for 4 weeks) or doxycycline (10 mg/
kg PO q12h for 4 weeks) and dihydrostrepto -
mycin (10 mg/kg IM q8h during weeks 1 and 
4). • Enrofloxacin (10–20 mg/kg PO q24h 
for 30 days)—not recommended: variable 
results.
Tetracyclines—do not use in immature animals.
Gentamicin—6–15 mg/kg IM/SC q12h; 
limited success; insufficient data on efficacy 
combined with tetracycline.
  FOLLOW-UP
• Serologic tests—monthly at least 3 months 
after completion of treatment; continuous, 
persistent decline in antibodies to negative 
status indicates successful treatment. 
• Recrudescent infections (rise in antibody 
levels, recurrence of bacteremia after therapy)—  
retreat, neuter and retreat, or euthanize. 
• Blood cultures—negative for at least 3 
months after completion of treatment.
• Vaccine—none. • Testing—all females 
before estrus if breeding is planned; breeding 
males at frequent intervals. • Quarantine and 
test all new dogs twice at monthly intervals 
before entering breeding kennel; test all 
breeding animals yearly.
• Owner reluctance to neuter or euthanize 
valuable dogs, regardless of treatment failure. 
• Remind owners of ethical considerations, 
obligation not to sell or distribute infected dogs.
• Prognosis guarded. • Infected for <3–4 
months—likely to respond to treatment. 
• Chronic infections—may not respond to 
therapy. • Discospondylitis—may need 
repeated or long-term drug treatment, rarely 
surgical intervention. • Combination therapy 
with gentamicin or streptomycin, doxycycline, 
enrofloxacin, and rifampin has successfully 
treated ocular disease in dogs. • Successfully 
treated (seronegative) dogs are susceptible to 
reinfection.  MISCELLANEOUS
• Human infections possible; usually mild 
flu-like symptoms. • Severe infections, 
including hepatomegaly, splenomegaly, 
meningitis, endocarditis reported in 
immunocompromised children and adults.
• Abortions at 45–60 days of gestation 
typical. • Pups from infected bitches may be 
infected or normal.
SYNONYMS
Contagious canine abortion.
• 2-ME = mercaptoethanol tube agglutination test.
• RSAT = rapid 2-mercaptoethanol slide 
agglutination test.
Greene CE, Carmichael LE. Canine brucel -
losis. In: Greene CE, ed., Infectious Diseases 
of the Dog and Cat, 3rd ed. St. Louis, MO: 
Saunders Elsevier, 2012, pp. 398–411.
Johnson CA, Carter TD, Dunn JR, et al. 
Investigation and characterization of 
Brucella canis infections in pet-quality dogs 
and associated human exposures during a 
2007–2016 outbreak in Michigan. JAVMA 
2018, 253:322–336.
Kauffman LK, Petersen CA. Canine 
brucellosis old foe and reemerging scourge. 
Vet Clin Small Anim 2019, 49:763–779.
Keid LB, Soares RM, Vasconcellos SA, et al. 
Comparison of agar gel immunodiffusion test, 
rapid slide agglutination test, microbiological 
culture, and PCR for the diagnosis of canine 
brucellosis. Res Vet Sci 2009, 86:22–26.
Author  Robyn Ellerbrock
Stephen C. Barr.
available online(continued)  Brucellosis

204  Blackwell’s Five-Minute Veterinary Consult  
C
  BASICS
OVERVIEW
• Calcipotriene, also known as calcipotriol, is 
a synthetic analogue of calcitriol, an active 
metabolite of Vitamin D3. • Calcitriol activity: 
• Anti-psoriatic—increases epithelial cell 
differentiation and decreases keratinocyte 
proliferation. • Promotes calcium retention—
triggers intestinal absorption, renal reabsorption, 
and mobilization of bone resorption of 
calcium. • Toxic exposure leads to 
hypercalcemia with soft tissue mineralization 
(hypercalcemic nephropathy), cardiac 
conduction disturbance, and gastrointestinal 
ulceration. • Cream, ointment, foam, and 
solution formulation for treatment of human 
psoriasis; common tradenames—Calcitrene®, 
Dovonex®, Sorilux®, Taclonex®. • Very low 
margin of safety—consider all exposures 
toxic. • Organ systems affected—
cardiovascular, endocrine/metabolic, 
gastrointestinal, musculoskeletal, nervous, 
renal/urologic.
Dogs and cats, with small or young animals at 
increased risk for toxicity.
SIGNS
• Early (0–24 hours)—vomiting, anorexia, 
diarrhea, depression, polyuria, polydipsia. 
• Late (18–72 hours)—hypercalcemia, 
hyperphosphatemia, azotemia/acute renal 
injury. • Other—bradycardia, arrhythmias, 
hematemesis, melena, abdominal pain, 
oliguria. • End stage—anuria, acute renal 
failure/dystrophic calcification of soft tissue, 
coma, death.
Toxic exposure occurs when pets chew 
product tube/bottle or lick skin of human 
where product has been applied.
  DIAGNOSIS
• Vitamin D toxicity—vitamin D 
supplements, cholecalciferol rodenticide. 
• Ethylene glycol toxicity. • Grape/raisin 
toxicity. • Renal failure—acute or chronic. 
• Infectious disease—blastomycosis, 
heterobilharziasis, histomoniasis, bacterial 
osteomyelitis. • Hypoadrenocorticism. 
• Hypercalcemia of malignancy. 
• Hyperparathyroidism, primary. 
• Idiopathic hypercalcemia of cats. • Large-
volume ingestion of calcinogenic plants—
Cestrum diurnum, Solanum malacoxylon . 
• Severe dehydration.CBC/CHEMISTRY/URINALYSIS
• Hyperphosphatemia. • Hypercalcemia. 
• Azotemia. • Hyposthenuria, isosthenuria. 
• Neutrophilia.
Ionized calcium preferred over serum 
calcium.
IMAGING
Thoracic and abdominal radiographs—
mineralization of soft tissue structure including 
kidneys, blood vessels, lungs, and intestine.
Coronary artery mineralization, gastrointestinal 
hemorrhage and mineralization, renal tubular 
necrosis and renal cortical mineralization, 
pulmonary mineralization.
  TREATMENT
• Therapy immediately post ingestion focuses 
on decontamination and serial monitoring; if 
hypercalcemia occurs, weeks-long therapy is 
necessary due to slow release of stored product 
from fat/muscle tissue. • Oral irrigation with 
water if patient has recently licked product. 
• Early emesis or gastric lavage. • Activated 
charcoal (1–2 gm/kg) with a cathartic × 1, 
followed by activated charcoal only q6–8h × 2 
doses; monitor sodium concentration. • Fluid 
therapy—if hypercalcemic: IV 0.9%NaCl 
rehydrate prn then 2× maintenance to 
encourage calciuresis; if normocalcemic: IV or 
SC fluids PRN to maintain hydration. 
• Diet— if hypercalcemic: calcium-restricted 
prescription diet or veterinary nutritionist-
guided homemade diet.
• Antiemetics PRN (e.g. maropitant 1mg/kg 
SC/IV, 2mg/kg PO q24h). • Proton pump 
inhibitor (e.g., omeprazole 1 mg/kg PO q24h) 
or H2 blocker (e.g., famotidine 1mg/kg IM/
IV/PO/SC q 12-24h; slow IV administration 
advised for cats). • Sucralfate (0.25–1g PO 
q8h on empty stomach). • Cholestyramine 
(0.3–1 g/kg PO q8h × 4 days post ingestion); 
may reduce enterohepatic recirculation of 
vitamin D by reducing reabsorption of vitamin 
D–bound bile acids. • If hypercalcemic: 
◦ T reatment goals—serum calcium <12.5 mg/
dL or ionized calcium <1.33 mmol/L. 
◦ Bisphosphonate tx (e.g., pamidronate 
sodium 1.3–2.0mg/kg diluted in 150cc saline 
IV CRI × 2–4 h or zoledronate 0.25 mg/kg in 
50cc saline IV CRI x 15 min); bisphosphonates 
block dissolution of calcium hydroxyapatite 
and inhibit osteoclastic bone resorption; 
reduction in calcium level seen in 1–3 days; rebound hypercalcemia may occur and repeat 
dosing necessary in 3–7 days. ◦ Prednisone 
1 mg/kg PO BID or dexamethasone 0.2 mg/
kg IV BID; initially or at a later time; wean 
slowly. • Furosemide 1 mg/kg PO BID or 
0.1–0.66mg/kg/h IV CRI- only in well-
hydrated patients. • If hyperphosphatemic - 
aluminum hydroxide: 30–90 mg/kg/day 
divided; with meals.
• Bisphosphonate use may result in hypo -
calcemia. • Long-term adverse effects from 
use of bisphosphonates in juvenile/growing 
dog or cat unknown.
  FOLLOW-UP
• Baseline CBC, serum chemistry, urinalysis; 
monitor renal values, hydration parameters, 
and calcium/phosphorous levels q12–24h × 4 
days minimum; if hypercalcemia/hyperphospha -
temia occurs continued monitoring of 
calcium/phosphorous, renal values, and 
hydration parameters advised until 
normalized—up to 3–4 weeks. • Urine 
output. • Appetite. • Heart rate/blood 
pressure.
• Do not allow pets to lick humans where 
calcipotriene was applied. • Keep medication 
inaccessible to pets.
Dystrophic mineralization of soft tissue, acute 
kidney failure, death.
Good prognosis if rapid, aggressive, and 
continuing therapy is provided and hypercalcemia/
hypophosphatemia minimized. Guarded to 
poor prognosis if soft tissue mineralization 
occurs. 
Gwaltney-Brant S, Calcipotriene/calcipotriol. 
In: Hovda LR, Brutlag A, Poppenga R, 
Peterson K, eds., Blackwell’s Five-Minute 
Veterinary Consult Clinical Companion: 
Small Animal Toxicology, 2nd ed. Ames, IA: 
Wiley-Blackwell, 2016, pp. 172–177.
Author  Susan Holland
Consulting Editor  Lynn R. HovdaCalcipotriene/Calcipotriol Toxicosis

Canine and Feline, Seventh Edition  205
C
  BASICS
OVERVIEW
• Calcium channel blockers (CCBs): class IV 
antidysrhythmics used to treat systemic 
hypertension, cardiac disease, tachydys­
rhythmias, and oliguric/anuric renal failure in 
dogs and cats. • CCBs inhibit movement of 
Ca through L ­type voltage ­gated slow Ca 
channels located on cardiac muscle, 
atrioventricular (AV) and sinoatrial (SA) 
nodes, vasculature smooth muscle, and 
pancreatic beta cells. • Three classes of 
CCBs—phenylalkylamine, benzothiazepine, 
dihydropyridine; CCB class determines the 
effect on the body.
SIGNS
Systems affected include: • Cardiovascular—
bradycardia, AV dissociation and AV block 
(first, second, or third degree), hypotension. 
• Gastrointestinal—vomiting, diarrhea, ileus. 
• Respiratory—pulmonary edema. 
• Nervous—decreased mentation, weakness, 
collapse, seizures. • Endocrine/metabolic—
hyperglycemia, metabolic acidosis secondary 
to hypoperfusion.
  DIAGNOSIS
• Beta blocker antagonist toxicosis. • Cardiac 
disease with bradyarrhythmias. 
clonidine, digoxin toxicosis). • Sedative 
overdose (e.g., opioid or baclofen toxicosis). 
• Sick sinus syndrome. • Hyperkalemia. 
• Hyperglycemia. • Azotemia and elevated 
liver enzymes with prolonged hypo  ­ 
Blood gas—metabolic acidosis.
IMAGING
Chest radiographs to evaluate for pulmonary 
edema with respiratory signs.
• ECG—first ­, second ­, and third ­degree AV 
block; prolonged PR, QRS, and QT intervals. 
  TREATMENT
• Emesis if asymptomatic and <2 hours after 
exposure. • Gastric lavage if decreased mental status and large number of pills ingested. 
• Temporary cardiac pacing when medical 
therapy fails. • IV fluid bolus over 15–20 min 
for hypotension—cats, 10–20 mL/kg; dogs, 
20–30 mL/kg.
• Activated charcoal (1–2 g/kg) PO, repeat 
activated charcoal for extended ­release (ER) 
formulations. • Atropine (0.02–0.04 mg/kg 
IV) for sinus bradycardia. • Calcium 
infusion—first ­line therapy despite normo­
calcemia to increase Ca availability for muscle 
function and improve contractility. ◦ Ca 
gluconate 10% bolus 0.5–1.5 mL/kg IV over 
5–10 min followed by CRI of 0.5–1.5 mL/
kg/h, titrated to effect; monitor continuous 
ECG and infusion should be slowed or 
stopped if bradycardia or conduction 
blockade worsens. ◦ Ca chloride 10% bolus 
0.15–0.5 mL/kg IV; central line 
recommended due to risk of tissue injury 
secondary to drug extravasation. 
lipid­soluble drugs, increase Ca available for 
muscle contraction, and provide an energy 
source for heart muscle. ◦ IFE 20% solution 
dose—1.5 mL/kg IV bolus over 1 min; follow 
with CRI of 0.25 mL/kg/min for 30–60 min; 
additional IV doses: 1.5 ml/kg every 4–6h or 
CRI of 0.5 mL/kg/h; monitor serum for 
lipemia every 2–4h to determine if additional 
dosing is needed. • High ­dose insulin 
euglycemia (HIE) treatment—may provide 
energy for heart muscle and increase Ca 
available for muscle contraction. 
Recommended treatment: ◦ Check blood 
glucose (BG) concentration and administer 
dextrose if BG <100 mg/dL. ◦ Administer 
regular insulin at 1 unit/kg IV, followed by 
CRI at 0.5–2 units/kg/h; may increase every 
10 min up to maximum dose of 10 units/
kg/h; when signs resolve, decrease insulin by 
1–2 units/kg/h. ◦ Monitor BG every 10 min 
while titrating insulin dose; once stabilized, 
check BG every 30–60 min; central line 
placement recommended for frequent glucose 
monitoring and dextrose administration 
during HIE treatment; dextrose supplemen­
tation will be needed to maintain normal BG 
concentrations and continued up to 24h after 
discontinuation of insulin therapy. ◦ Monitor 
potassium concentration every hour during 
titration, then every 6h; administer potassium 
chloride to keep potassium concentrations 
within normal range. • Glucagon—may not 
be as effective as HIE or IFE; dose is 
0.05–0.2 mg/kg slowly IV bolus, followed by 
CRI of 0.05–0.1 mg/kg/h.CONTRAINDICATION/POSSIBLE 
patients less response to other therapy.
  FOLLOW-UP
Monitor heart rate/ECG, BP , and BG for 
6–12h with immediate ­release preparations 
and 12–24h for ER/sustained ­release (SR) 
preparations, depending on peak drug levels.
• Ingestion of immediate ­release preparations 
typically result in clinical signs in 8–12h. 
• SR or ER preparations may take 12–24h 
for clinical signs to develop. • Prognosis 
depends on dose ingested and response to 
therapy. • Toxicosis normally results in 
bradycardia, hypotension, and in severe cases 
decreased mental status, coma, and apnea.
• CCB = calcium channel blocker.
• HIE = high ­dose insulin euglycemia.
• IFE = Intravenous fat emulsion.
• SA = sinoatrial.
Hayes CL, Knight M. Calcium channel 
blocker toxicity in dogs and cats. Vet Clin 
North Am Small Anim Pract 2012: 
42:263–277.
available onlineCalcium Channel Blocker Toxicosis

206  Blackwell’s Five-Minute Veterinary Consult  
C
  BASICS
OVERVIEW
• Campylobacter jejuni —fastidious, 
microaerophilic, Gram-negative curved 
bacteria; often isolated from healthy dogs and 
cats; may cause superficial erosive entero -
colitis. • Infection—fecal–oral route from 
contaminated food, water, raw meat 
(especially chicken), environment; localized 
in crypts of intestine; motile; produces 
multiple enterotoxins. • Invasion of gut 
mucosa—hematochezia, inflammation, 
ulceration, edema; bacteria shed in feces for 
weeks to months. • Up to 49% of dogs 
without diarrhea and 45% of normal cats 
carry C. jejuni  and shed it in feces.
• Dogs; less commonly cats. • Prevalence—
higher in puppies and kittens up to 6 months. 
• Can cause chronic disease.
SIGNS
• Diarrhea—varies; mucoid and watery, 
hemorrhagic; may be chronic. • Tenesmus. 
• Fever, anorexia, intermittent vomiting 
possible. • Adults—may be asymptomatic 
carriers. • Abortion and perinatal death.
• C. jejuni , C. coli , C. upsaliensis , C. 
helviticus , C. lari , and more uncommon 
species. • Kennels/intensive housing, poor 
sanitation/hygiene, fecal contamination in 
environment. • Young animals—debilitated, 
immunosuppressed, parasitized. 
• Nosocomial infection in hospitalized 
patients. • Adults—concurrent intestinal 
infections (e.g., Salmonella , parvovirus, 
hookworms). • Feeding homemade or 
commercially available raw meat–based 
diets.
  DIAGNOSIS
• Bacterial enterocolitis— Salmonella , Yersinia 
enterocolitica , Clostridium difficile , Clostridium 
perfringens . • Parasitic—helminths (whipworms); 
protozoa ( Giardia , Isospora ). • Viral—
parvovirus; signs often more severe. • Dietary 
indiscretion, intolerance. • Drugs, toxins. 
• Pancreatitis. • Intussusception, other causes 
of abdominal pain. • Distinguish from other 
causes of chronic diarrhea. • Primary 
intestinal disease.
• Leukocytosis—possible. • Biochemistry 
abnormalities—effects of diarrhea, 
dehydration (e.g., azotemia, electrolyte 
disturbances).DIAGNOSTIC PROCEDURES
• Fecal leukocytes—in gastrointestinal tract 
and stool. • Fecal culture—submit feces in 
Amies transport medium with charcoal or 
Cary-Blair medium kept refrigerated at 4 °C 
in transit. • Species-specific quantitative 
PCR—current methodology may be biased to 
detect C. jejuni  and C. coli .
Direct Examination of Feces
• Gram stain—make smear; leave Gram 
safranin on for longer period. • Wet 
mount—large numbers of highly motile 
bacteria (characteristic darting motility).
• Gross—diffuse colon thickening, 
congestion/edema; hyperemia of small 
intestine; enlarged mesenteric lymph nodes. 
• Thickening of intestinal smooth muscle in 
cats.
  TREATMENT
Mild Enterocolitis
• Outpatient. • Usually self-limiting.
Severe Enterocolitis
• Inpatient, especially if very young, fever, 
hematochezia, melena. • Severe neonatal 
disease—isolate; aggressive therapy. • NPO 
for 24 hours; then bland diet. • Mild 
dehydration—oral fluid therapy with enteric 
fluid replacement solution. • Severe 
dehydration—intravenous fluid therapy with 
balanced isotonic replacement solution. 
• Plasma transfusion may be required. 
• Locally acting intestinal adsorbents/
protectants.
• Antibiotics—for systemic illness (e.g., high 
fever, dehydration), when diarrhea or 
abnormal clinical signs persist >7 days, in 
immune-suppressed patients. • Erythromycin 
10–20 mg/kg PO q8h for 5 days; drug of 
choice. • Enrofloxacin—dog, 10 mg/kg PO/
IV/IM q24h; cat, 5 mg/kg PO/IM/IV q24h. 
• Tylosin 11 mg/kg PO q8h for 7 days. 
• Septicemia—parenteral broad-spectrum 
antibiotics indicated. • Multidrug resistance 
(vs. macrolides, quinolones) becoming more 
common.
• Antidiarrheal drugs that reduce intestinal 
motility are contraindicated. • Enrofloxacin—  
may induce arthropathy in dogs <28 weeks of 
age; caution with use in cats.  FOLLOW-UP
Repeat fecal culture after treatment.
• Good hygiene (hand washing). • Routinely 
clean and disinfect runs, food and water 
bowls. • Do not feed raw-meat diets to 
companion animals.
• Adults—usually self-limiting. • Juveniles 
with severe or persistent enterocolitis—
prognosis good with appropriate intervention.
Concurrent infection with other pathogenic 
bacteria, enteric parasites, viruses.
High ( C. jejuni , C. coli , C. upsaliensis ).
Erythromycin—safe in early pregnancy.
http://www.cfsph.iastate.edu/DiseaseInfo/
disease.php?name=campylobacteriosis&l 
ang=en
Acke E. Campylobacteriosis in dogs and cats: 
a review. N Z Vet J 2018, 66:221–228.
Marks SL, Rankin SC, Byrne BA, et al. 
control. J Vet Intern Med 2011, 
25:1195–1208.
Montgomery MP , Robertson S, Koski L, et al. 
MDR Campylobacter jejuni outbreak 
linked to puppy exposure. MMWR Morb 
Mortal Wkly Rep. 2018, 67:1032–1035.
Author  Patrick L. McDonough
Consulting Editor  Amie KoenigCampylobacteriosis

Canine and Feline, Seventh Edition  207
C
  BASICS
OVERVIEW
• Candida —dimorphic fungus with the yeast 
phase ( Candida  spp.) being part of the normal 
flora of the mouth, nose, ears, and gastrointestinal 
(GI) and urogenital tracts of dogs and cats.
• C. albicans  and C. parapsilosis  most 
commonly cultured from clinically healthy 
dogs.
• Recovery from mucosal surfaces does not 
imply disease; organisms may cause oppor­
tunistic infection, colonize damaged tissues, or 
invade normal tissues of immunosuppressed 
animals.
• Pathogenic role determined by infiltration 
of organisms into tissues, or detection of 
organisms in presumed sterile sites (e.g., 
urinary bladder, peritoneal cavity).
• Organ systems most affected include GI, 
renal/urologic, skin, and respiratory.
• Conditions that suppress the immune 
system (e.g., feline immunodeficiency virus 
[FIV] infection) increase the likelihood of 
isolation in asymptomatic animals.
Cats and dogs—any age and breed.
SIGNS
• Nonhealing ulcers in the oral, upper 
respiratory, GI, or urogenital mucosa—signs 
reflect location/extent of disease:
◦ Cystitis—hematuria, stranguria, and 
pollakiuria. 
◦ Otitis—head shaking, scratching.
◦ Oral cavity—drooling.
• Inflammation around IV catheters or 
gastrotomy tubes.
• Ulcerative, red skin lesions.
• Systemic disease with fever, cardiac and/or 
neurologic abnormalities can be seen.
• Infection—rare; associated with neutro­
penia, parvovirus or FIV infection, 
endocrinopathies, glucocorticoid therapy, 
gastrotomy tubes, indwelling urinary 
catheters/urethrostomy, IV catheters, and 
incomplete bladder emptying.
• Lower urinary tract disease may predispose 
to candiduria.
• Administration of antibiotics in prior 30 days.
• Occasionally local or systemic infection is 
seen in animals without predisposing 
• Skin damaged by burns, trauma, or 
necrotizing dermatitis.  DIAGNOSIS
Considered whenever the primary condition 
does not respond as expected.
• Reflect underlying inflammation and organ 
involvement (unless neutropenic).
• Urinalysis—may show yeast or clumps of 
mycelial elements (pseudohyphae) with 
inflammatory cells; concurrent bacterial 
urinary tract infection common.
• Cytology—spherical to oval yeast cells 
5–7 μm in diameter; pseudohyphae and 
septate hyphae 3–5  μm wide.
• Culture—grows well on blood agar and 
often is isolated from specimens submitted 
for bacterial culture; more easily isolated from 
urine than blood.
• PCR and antigen tests available.
• Lesions—to determine if Candida  is truly a 
pathogen, requires demonstration of 
organisms penetrating the tissues.
• Urine sample—cystocentesis; culture of 
multiple colonies of Candida  supports 
• Otitis (dogs)—culture of Candida  spp. or 
identification of yeast or mycelial elements on 
ear cytology suggests diagnosis.
• In febrile patients, culture catheter tips.
• White caseous foci in the infected tissue.
• Large numbers of both yeast and pseudo ­ 
hyphae in tissues surrounded by necrosis and 
suppurative inflammatory reaction.
• May be pyogranulomatous in more chronic 
  TREATMENT
• T reat underlying causes of 
immunosuppression.
• Remove indwelling catheters, if possible.
• Topical therapy (mucosal lesions)—nystatin 
or amphotericin B.• Fluconazole—5 mg/kg PO q12h; very 
effective and excreted unchanged in urine (high 
concentration in commonly infected sites).
• Itraconazole—5–10 mg/kg PO q12h; 
effective, can use if organism resistant to 
fluconazole; not recommended for urinary tract 
infection (poor urinary excretion).
• In lower urinary tract Candida  infections 
resistant to fluconazole—infuse 10–30 mL of 
1% clotrimazole into the bladder every other 
day for three treatments.
• Candida  may develop drug resistance—
consider drug sensitivity testing if suspected.
• Caspofungin—may be option for resistant 
isolates.
  FOLLOW-UP
• Fluconazole and itraconazole—hepatic 
toxicity; monitor serum alanine aminotransferase 
(ALT) activity monthly initially and check if 
patient becomes anorexic.
• After signs have resolved—reculture sites of 
infection; continue treatment for 2 weeks 
beyond negative culture; repeat cultures 2 weeks 
after completion of treatment and again if signs 
recur.
• Should resolve within 2–4 weeks of treatment 
with correction of immunosuppression.
• Control of the underlying disease is 
necessary to prevent recurrence.
• May resolve spontaneously if the underlying 
condition is corrected.
Genetic similarities between human and 
animal isolates suggest a potential for transfer 
of C. albicans  between species.
Reagan KL, Dear JD, Kass PH, et al. Risk 
factors for Candida urinary tract infections 
in dogs and cats. J Vet Intern Med 2019, 
33:648–653.
Consulting Editor  Amie KoenigCandidiasis

208  Blackwell’s Five-Minute Veterinary Consult  
CCanine Coronavirus Infections
  BASICS
OVERVIEW
• Canine enteric coronavirus (CCoV)—
sporadic outbreaks of enteritis in dogs; 
worldwide distribution.
• Canine pantropic coronavirus (CPCoV)—
variant of CCoV, fatal disease in dogs <6 
months, described principally in Europe.
• CCoV, CPCoV—closely related to feline 
infectious peritonitis (FIP) virus, feline 
enteric coronavirus.
• Canine respiratory coronavirus (CRCoV)—
associated with canine infectious respiratory 
disease complex (kennel cough); worldwide 
distribution; genetically and serologically 
distinct from CCoV.
• Incubation period 1–3 days.
• CCoV infection—usually inapparent; mild to 
severe enteritis possible; death reported in young 
pups; infects upper two-thirds of small intestine 
and associated lymph nodes; crypt cells spared.
• Simultaneous infection with canine parvo  - 
virus (CPV)-2 possible; severe, often fatal.
• CPCoV—infects intestinal tract, after short 
viremia distributes to organs like spleen, lungs, 
brain.
• Coronaviruses undergo rapid evolution, are 
highly variable; differences in virulence likely 
between isolates.
• Dogs of all ages, breeds; disease more severe 
in young.
• CRCoV infections more common in 
winter, in shelters.
SIGNS
• Vary greatly—CPCoV virulent isolates 
cause systemic disease.
• Adults—most infections inapparent.
• Puppies—mild to severe, occasionally fatal, 
enteritis.
• Diarrhea—may be explosive; yellow-green or 
orange; loose or liquid; typically malodorous 
(characteristic); may persist for days to >3 
weeks; may recur; young dogs may suffer 
severe, protracted diarrhea, dehydration.
• Coughing, dyspnea—CRCoV associated 
with kennel cough complex.
• Anorexia, lethargy.
• For CPCoV—pyrexia, anorexia, depression, 
vomiting, hemorrhagic enteritis, respiratory 
distress, and leukopenia that persists >1 week; 
ataxia, seizures, and death also possible.
• Stress—greatest risk; sporadic outbreaks 
have occurred in dogs attending shows, in 
kennels where new dogs frequently intro -
duced; crowding and unsanitary conditions 
promote illness.
• For CCoV, CPCoV—feces primary source 
of infection; virus shed for 2 weeks.• For CRCoV—respiratory secretions, 
fomites likely sources of infection.
  DIAGNOSIS
• Infections caused by enteric bacteria, 
protozoa, other viruses; canine kennel cough 
complex pathogens.
• Other mild to moderate upper respiratory 
disease.
• Food intoxication or intolerance.
Normal; lymphopenia with more virulent 
CCoV isolates.
Serologic tests—available; not standardized, 
difficult to interpret due to frequent asympto  - 
matic infection.
• Viral isolation for CCoV, CRCoV—
possible but not recommended.
• Specific reverse transcriptase polymerase 
chain reaction (RT-PCR)—using feces for 
CCoV, respiratory swabs for CRCoV; 
CPCoV defined by presence of virus in 
extraintestinal organs.
• Immunofluorescence of small intestine—
fatal cases; may show viral antigen in cells 
lining villous epithelium.
• Gross—dilated small intestine filled with 
gas, watery green-yellow material.
• Bowel loops congested, hemorrhagic; 
mesenteric lymph nodes enlarged, 
edematous.
• Histopathology—atrophy and fusion 
of intestinal villi, deepening of crypts, 
increased cellularity of lamina propria, 
epithelial cell flattening, increased goblet 
cells.
• CPCoV—hemorrhagic lesions in various 
organs (lungs, small intestines, spleen, lymph 
nodes).
  TREATMENT
• Most dogs recover without treatment.
• CCoV—fluid, electrolyte treatment if 
dehydration severe.
• CRCoV—as for canine kennel cough 
complex.
Antibiotics—not usually indicated, except 
with enteritis, sepsis, severe respiratory illness.  FOLLOW-UP
• CCoV vaccines—controversial; inactivated 
and live viral vaccines; appear safe; moderate 
efficacy may be due to variability of CCoV 
strains; not recommended; do not cross-
protect against CPCoV, CRCoV.
• Strict quarantine, sanitation essential in 
kennels: susceptible to common disinfectants.
• CCoV, CRCoV—highly contagious; spread 
rapidly.
Diarrhea with CCoV—may persist 10–12 
days, may recur.
• Prognosis—good, except severe infections 
of young pups.
• Majority recover after short illness.
• Concurrent infection with CPV or other 
agent.
• Infections with other respiratory pathogens 
with CRCoV.
• CCoV = canine enteric coronavirus.
• CPCoV= canine pantropic coronavirus.
• CPV = canine parvovirus.
• CRCoV = canine respiratory coronavirus.
• RT-PCR = reverse transcriptase polymerase 
Decaro N, Cordonnier N, Demeter Z, et al. 
European surveillance for pantropic canine 
coronavirus. J Clin Microbiol 2013, 
51:83–88.
Mitchell JA, Cardwell JM, Leach H. European 
surveillance of emerging pathogens associated 
with canine infectious respiratory disease. Vet 
Microbiol 2017, 212:31–38.
Author  Sophie Le Poder
John S. Parker.

Canine and Feline, Seventh Edition  209
C
Canine Degenerative Myelopathy
  BASICS
Canine progressive adult-onset fatal neurode-
generative disease that has recently been 
shown in many breeds to be a result of a 
mutation in the superoxide dismutase 1 gene 
(SOD1 ). Mutations in SOD1  are known to 
cause some forms of amyotrophic lateral 
sclerosis (ALS), also known as Lou Gehrig’s 
disease. Initial signs of progressive upper 
motor neuron spastic paresis and general 
proprioceptive ataxia in the pelvic limbs occur 
in older dogs. If euthanasia is delayed, clinical 
signs progress to flaccid tetraparesis/plegia 
and other lower motor neuron signs.
• A c.118 G>A  transition in Exon 2 of SOD1  
that predicts an E40K missense mutation 
underlies most degenerative myelopathy (DM); 
a second SOD1  missense mutation ( c.52 A>T ) 
has been seen only in Bernese mountain dogs.
• Lesions may represent a multisystem 
central-peripheral axonopathy.
• Predilection for lesion severity in mid-
thoracic spinal cord may be a result of lower 
percentages of radicular artery contributions 
and small-diameter vessels when compared to 
other spinal cord regions.
• Paucity of vascular supply in thoracic spinal 
cord may predispose it to damage from 
oxidative and metabolic disturbances.
• Central and peripheral nervous systems.
• Thoracolumbar spinal cord in early stage.
• Progresses to involve the cervical and 
lumbar spinal cord and peripheral nervous 
system later in the course of the disease.
• Neurons in the brainstem also may be affected.
• Disease also involves the sensory nerve roots 
and dorsal root ganglia.
GENETICS
• Most commonly autosomal recessive 
inheritance.
• Due to preponderance of purebred dogs 
affected, a familial inheritance is currently 
• Mutations in SOD1  are causative for DM 
but are incompletely penetrant.
• Dogs that are homozygous for the mutant 
allele are at highest risk  for developing DM; not 
all dogs that test homozygous for the mutation 
will develop DM, but dogs that test normal 
(clear) are highly unlikely to develop DM; dogs 
that test carrier are less likely to develop DM, 
but this has been documented in some breeds.
Prevalence rate of DM reported for all dogs 
collected from the Veterinary Medical 
Database (1990–1999) was 0.19%.GEOGRAPHIC DISTRIBUTION
Worldwide
So far the DM-associated SOD1:c.118A  allele 
is in >150 breeds or varieties; a second SOD1  
mutation ( c.52 A>T ) was found only in 
Bernese mountain dogs. DM has been 
histopathologically confirmed in many 
purebred and mixed-breed dogs.
• Mean—9 years of age in large dogs; mean 
age at onset is 11 years in Pembroke Welsh 
corgi.
• Range—between 8 and 14 years.
No known sex predilection.
SIGNS
• Early:
◦ Upper motor neuron paraparesis.
◦ Insidious, progressive, asymmetric 
general proprioceptive ataxia; gait shows 
long-strided spastic paraparesis.
◦ Paw replacement deficits.
◦ Spinal reflexes usually present or 
exaggerated (patellar reflex may be 
reduced).
◦ Presence of crossed-extensor reflex is 
variable.
◦ Lack of paraspinal hyperesthesia is key 
clinical feature.
• Later:
◦ Pelvic limb paresis leading to plegia, 
eventually progressing to tetraparesis/
plegia.
◦ Mild to moderate loss of muscle mass in 
pelvic limbs due to neurogenic atrophy.
◦ Reduced spinal reflexes in pelvic limbs.
◦ ± Urinary and fecal incontinence.
• End stage:
◦ Flaccid tetraplegia.
◦ Difficulty with swallowing and tongue 
movements.
◦ Absence of spinal reflexes in all limbs.
◦ Reduced to absent cutaneous trunci 
reflex.
◦ Profound generalized muscle wasting.
◦ Urinary and fecal incontinence.
CAUSES
• Hereditary disease and genetic predi  - 
sposition.
• Other hypothesized causes include 
immune-mediated, metabolic deficiencies, 
toxic, and oxidative stress.
• Dogs homozygous for the mutant allele(s) 
are at highest risk.
• There may be other environmental factors 
and modifying genes; studies underway.  DIAGNOSIS
• Type II intervertebral disc herniation.
• Intramedullary spinal cord neoplasia.
• Degenerative lumbosacral stenosis.
• Hip dysplasia.
• Other coexisting orthopedic disease.
• Performed to rule out other underlying 
metabolic disease.
• Urinalysis may identify secondary urinary 
tract infection.
• Urine culture and sensitivity testing.
• Thyroid function testing.
• Electrodiagnostic testing results are normal 
in early diagnosis of DM.
• Genetic testing—test result of at-risk can 
support a presumptive diagnosis of DM in 
light of typical clinical signs and normal 
findings on neuroimaging and cerebrospinal 
fluid analysis.
IMAGING
• Survey spinal radiography.
• Myelography evaluates for compressive 
spinal cord disease.
• Myelography combined with CT—more 
sensitive technique to evaluate suspicious 
lesions.
• MRI—preferred technique to evaluate for 
extramedullary compressive and intramedul-
lary lesions.
• CSF analysis evaluates for inflammatory 
disease.
• Definitive diagnosis is determined by 
post-mortem histopathology of spinal cord.
• Spinal cord axons and myelin affected most 
severely in dorsal and dorsal portion of lateral 
funiculi.
• Vacuolated axon cylinders/myelin sheaths 
most extensive in mid-thoracic spinal cord.
• Astroglial proliferation is prominent in 
severely affected areas of lesion distribution.
• Usually, lesion distribution is described as 
asymmetric and discontinuous; however, 
more recent evidence describes lesion distrib -
ution as symmetric and continuous in dogs 
that survive for long periods with DM.
• Neuronal cell body loss in ventral horn is 
evident at terminal or end-stage disease.
• Nerve specimens show fiber loss resulting 
from axonal degeneration and secondary 
demyelination.
• Muscle specimens show large and small 
groups of atrophic fibers typical of denervation.

210  Blackwell’s Five-Minute Veterinary Consult  
C
  TREATMENT
• Supportive care.
• Breeds of small size may survive longer with 
DM because the pet owner is able to more 
easily give the appropriate care.
• When dog becomes nonambulatory, keep 
on a well-padded surface to prevent decubitus 
ulceration over bony prominences.
• Keep hair trimmed, and skin clean and 
dry to prevent urine scald secondary to 
incontinence.
• Urine should be monitored for odor and 
color change, which may indicate urinary 
• Physical therapy using range-of-motion and 
active exercises may help maintain limb 
mobility and muscle strength.
ACTIVITY
• Exercise is encouraged to slow disuse 
atrophy of pelvic limbs, but fatigue should 
be monitored and exercise intensity 
adjusted.
• Hydrotherapy can involve use of an 
underwater treadmill setup.
• A wheel cart may assist with patient 
mobility.
DIET
• Maintain balanced diet.
• Prevent weight gain.
• Long-term prognosis is poor.
• Meticulous nursing care is crucial to 
preventing secondary complications in a 
recumbent patient.
None
Clinical trials are underway to determine 
effectiveness in slowing or halting disease 
progression.  FOLLOW-UP
• Repeat neurologic examinations.
• Urine retention.
• Urinalysis and urine culture to monitor for 
urinary tract infection.
• Decubitus ulceration.
• Dermatitis from urine scald.
• Urine retention may predispose to urinary 
• Local skin infections from decubitus ulceration.
• Nonambulatory paraparesis occurs within 
9–12 months from time of onset of signs.
• Tetraparesis may be evident within 3 years 
from time of onset of signs.
• Other neurologic diseases associated with 
old-age onset.
• Spinal cord neoplasia.
• Orthopedic disease.
Older dogs commonly affected.
None
N/A
SYNONYMS
• Canine ALS.
• DM.
• Degenerative radiculomyelopathy.
• German Shepherd dog myelopathy.
SEE ALSO
• Intervertebral Disc Disease, Cervical.• Intervertebral Disc Disease, Thoracolumbar.
• Lumbosacral Stenosis and Cauda Equina 
Syndrome.
• ALS = amyotrophic lateral sclerosis.
• DM = degenerative myelopathy.
• SOD1  = superoxide dismutase 1.
• www.caninegeneticdiseases.net/dm/
maindm.htm
• www.ofa.org/diseases/dna-tested-diseases/dm
Awano T, Johnson GS, Wade C, et al. 
Genome-wide association analysis reveals a 
SOD1  missense mutation canine degenera-
tive myelopathy that resembles amyotrophic 
lateral sclerosis. Proc Natl Acad Sci USA 
2009, 106:2794–2799.
Coates JR, March PA, Ogelsbee M, et al. 
Clinical characterization of a familial 
degenerative myelopathy in Pembroke 
Welsh Corgi dogs. J Vet Intern Med 2007, 
21:1323–1331.
Coates JR, Wininger FA. Canine degenerative 
myelopathy. Vet Clin North Am Small 
Anim Pract 2010, 40:929–950.
March PA, Coates JR, Abyad R, et al. 
Degenerative myelopathy in 18 Pembroke 
Welsh Corgi dogs. Vet Pathol 2009, 
46:241–250.
Ogawa M, Uchida K, Yamato O, et al. 
Neuronal loss and decreased GLT-1 
expression observed in the spinal cord of 
Pembroke Welsh Corgi Dogs with canine 
degenerative myelopathy. Vet Pathol 2014, 
51:591–602.
Wininger FA, Zeng R, Johnson GS, et al. 
Degenerative myelopathy in a Bernese 
Mountain Dog with a novel SOD1  missense 
mutation. J Vet Intern Med 2011, 
25:1166–1170.
Zeng R, Coates JR, Johnson GC, et al. Breed 
distribution of SOD1  alleles previously 
associated with canine degenerative myelopa -
thy. J Vet Intern Med 2014, 28:515–521.
Author  Joan R. Coates
available onlineCanine Degenerative Myelopathy  (continued)

Canine and Feline, Seventh Edition  211
C
Canine Distemper
  BASICS
• Acute to subacute, contagious, febrile, often 
fatal disease with respiratory, urogenital, 
gastrointestinal, ocular, and CNS manifest- 
ations.
• Caused by canine distemper virus (CDV), a 
Morbillivirus  in the Paramyxoviridae  family.
• Affects many Carnivora species; mortality 
rate varies greatly.
• Natural route of infection—airborne and 
droplet exposure; from nasal cavity, pharynx, 
and lungs, virus replication occurs in local 
lymph nodes; within 1 week, viral shedding 
occurs (mainly in respiratory exudates but also 
urine) and virtually all lymphatic tissues 
become infected; spreads via viremia to surface 
epithelium of respiratory, gastrointestinal, and 
urogenital tracts and to CNS.
• Disease progression depends on virus strain 
and host immune response:
◦ Strong cellular and humoral immune 
response—subclinical infection.
◦ Weak immune response—subacute 
infection; longer survival.
◦ Failed immune response—death within 
2–4 weeks after infection; frequently due to 
CNS manifestations.
• Viral excretion can occur for up to 2–3 months.
• Multisystemic—all lymphatic tissues, 
surface epithelium in respiratory, alimentary, 
and urogenital tracts, skin, endocrine and 
exocrine glands.
• CNS—brain and/or spinal cord.
• Dogs—sporadic outbreaks.
• Wildlife (raccoons, skunks, fox, tigers)—
fairly common.
Worldwide
Species
Most species of the order Carnivora; has been 
reported in large exotic cats.
Young, especially unvaccinated animals are 
most susceptible.
SIGNS
• Fever—intermittent peaks starting 3–6 days 
after infection.
• Gastrointestinal and/or respiratory signs—
nasal and ocular discharge, depression, 
anorexia, vomiting, diarrhea; often exacer -
bated by secondary bacterial infection.
• CNS—common; generally after systemic 
disease (depends on virus strain).◦ Gray matter disease—affects cerebral 
cortex, brainstem, and spinal cord and may 
cause a nonsuppurative meningitis, 
seizures, mentation change, and ataxia; 
dogs may die in 2–3 weeks; some dogs 
recover (associated with prompt humoral 
and cell-mediated immunity), others 
develop white matter disease.
◦ White matter disease—multifocal disease, 
commonly cerebellovestibular signs, paresis, 
ataxia, occasionally myoclonus; some dogs 
die 4–5 weeks after initial infection with 
noninflammatory, demyelinating disease; some 
dogs may recover with minimal CNS injury.
• Optic neuritis and retinal lesions may 
occur; anterior uveitis, keratoconjunctivitis 
sicca possible.
• Hardening of footpads (hyperkeratosis) and 
nose—some virus strains; uncommon.
• Enamel hypoplasia of teeth after neonatal 
CAUSES
• CDV exposure.
• Incompletely attenuated vaccines (rare).
Contact of nonimmunized animals with 
CDV-infected animals (dogs, wild carnivores).
  DIAGNOSIS
• Diagnosis based on clinical suspicion; 
combination of respiratory and gastrointestinal, 
± CNS disease, in unvaccinated dog.
• Respiratory signs—can mimic kennel cough.
• Enteric signs—differentiate from canine 
parvovirus, coronavirus, parasitism (giardiasis), 
bacterial infections, gastroenteritis from toxin 
ingestion, inflammatory bowel disease.
• CNS form—differentiate from auto -
immune meningoencephalitis (granulomatous 
meningoencephalomyelitis, necrotizing 
encephalitis, meningoencephalitis of 
unknown etiology), protozoal (e.g., 
toxoplasmosis, neosporosis), fungal (e.g., 
cryptococcosis), and rickettsial (e.g., 
ehrlichiosis, Rocky Mountain spotted fever) 
meningoencephalitis, rabies.
Lymphopenia in early infection; rare 
thrombocytopenia; intracytoplasmic 
inclusions in white and red blood cells.
• Serology—positive antibody tests do not 
differentiate between vaccination and 
exposure to virulent virus; patient may die 
from acute disease before neutralizing 
antibody is produced. Immunoglobulin (Ig) 
M responses may occur up to 3 months after 
exposure to virulent virus, up to 3 weeks after 
vaccination; rising IgG titers in unvaccinated dog are suggestive of infection; may be useful 
for risk assessment of clinically healthy dogs 
in shelter environment.
• CDV antibody in cerebrospinal fluid 
(CSF)—indicative of distemper encephalitis, 
false negatives possible.
IMAGING
• Radiographs—evaluate pulmonary disease.
• CT and MRI—may or may not show 
lesions; MRI sensitive for demyelination.
• Immunohistochemical detection in haired 
skin, nasal mucosa, and footpad epithelium.
• Viral antigen or viral inclusions—in buffy 
coat cells, urine sediment, conjunctival or 
vaginal imprints, trans-tracheal wash 
(negative results do not rule out CDV).
• Reverse transcriptase polymerase chain 
reaction (RT-PCR)—on buffy coat, urine 
sediment cells, respiratory secretions, 
conjunctival swabs, CSF; false negatives 
possible, false positives with recent 
vaccination (uncommon).
• CSF—moderate mononuclear pleocytosis, 
elevated concentrations of CDV-specific 
antibody, interferon, and viral antigen early in 
disease course.
Gross
• Thymus—greatly reduced in size (young 
animals); sometimes gelatinous.
• Lungs—patchy consolidation.
• Footpads, nose—hyperkeratosis.
• Mucopurulent discharges—from eyes and 
nose, bronchopneumonia, catarrhal enteritis, 
skin pustules (secondary bacterial infection).
Histologic
• Intracytoplasmic eosinophilic inclusion 
bodies—in epithelium of bronchi, stomach, 
urinary bladder; also in reticulum cells and 
leukocytes in lymphatic tissues.
• Inclusion bodies in glial cells and neurons—
frequently intranuclear; also in cytoplasm.
• Immunofluorescence and/or immunocyto -
chemistry, virus isolation, and/or RT-PCR 
performed on tissues from lungs, stomach, 
urinary bladder, lymph nodes, brain.
  TREATMENT
Inpatient medical management to intensive 
care as indicated; isolate patient to prevent 
spread to other dogs.
• Symptomatic.
• IV fluids—for hypovolemia, support.
• Oxygen therapy, nebulization, and 
coupage—for pneumonia.
• Clean ocular, nasal discharges.

212  Blackwell’s Five-Minute Veterinary Consult  
CACTIVITY
Limited, to reduce spread.
DIET
Depends on extent of gastrointestinal 
• Inform client that mortality rate is about 50%.
• Inform client that dogs appearing to recover 
from early catarrhal signs may develop fatal 
CNS disease.
• Presenting neurologic abnormalities usually 
not reversible.
• Antiviral drugs—none known to be effective.
• Broad-spectrum antibiotics—for secondary 
bacterial infection (CDV is immuno -
suppressive), beta-lactams or cephalosporins 
are good initial choices.
• Anticonvulsant therapy—phenobarbital, 
potassium bromide, levetiracetam.
• Myoclonus—no proven treatment; single 
case report describes use of botulinum toxin 
type A.
Corticosteroids—use anti-inflammatory 
dosages with caution; may provide short-term 
control. Immunosuppressive dosages may 
enhance viral dissemination.
Tetracycline, fluoroquinolones—avoid in 
growing animals.
  FOLLOW-UP
• Monitor for CNS abnormalities, partic -
ularly seizures.
• Monitor for respiratory distress or 
dehydration in acute phase.
• Vaccination.
• Isolate puppies to prevent infection from 
wildlife (e.g., raccoons, foxes, skunks), 
CDV-infected dogs, ferrets.
• Recovered dogs may shed virus for up to 4 
months; isolate for this time period or until 
multiple negative RT-PCR tests.
Vaccines
• Duration of immunity from most vaccines 
is >3 years.• Modified live vaccine for CDV (MLV-CD)—  
prevents infection and disease; two types 
available:
◦ Canine tissue culture-adapted vaccines 
(e.g., Rockborn strain)—induce complete 
immunity in virtually 100% of susceptible 
dogs; rarely, a postvaccinal fatal encephalitis 
develops 7–14 days after vaccination, 
especially in immunosuppressed animals.
◦ Chick embryo-adapted vaccines (e.g., 
Lederle strain)—safer; postvaccinal 
encephalitis does not occur; only about 
80% of susceptible dogs seroconvert.
◦ Other species—chick embryo can safely 
be used in variety of wildlife species (e.g., 
gray fox); Rockborn type fatal in these 
animals.
• Killed vaccines—useful for species in which 
either type of MLV-CD is fatal (e.g., red 
panda, blackfooted ferret).
• Canarypox recombinant CDV vaccine.
Maternal Antibody
• Important.
• Most puppies lose protection from 
maternal antibody at 6–12 weeks of age; 2–3 
vaccinations should be given during this 
period.
• Heterotypic (measles virus) vaccination—
recommended for puppies that have maternal 
antibody; induces protection from disease but 
not from infection.
Possibility of CNS signs developing for 2–3 
months after catarrhal signs have subsided.
• Depends on strain and individual host 
response—subclinical, acute, subacute, fatal, 
or nonfatal infection.
• Mild CNS signs—patient may recover; 
myoclonus may continue for several months 
or indefinitely.
• Death—2 weeks to 3 months after 
infection; mortality rate ~50%.
• Euthanasia—owner may elect if or when 
neurologic signs develop; indicated if 
uncontrollable seizures occur.
• Persistent or latent Toxoplasma gondii  
infections—may be reactivated due to 
immunosuppressive state.
• Respiratory infections with Bordetella 
bronchiseptica  (kennel cough).AGE-RELATED FACTORS
• Young puppies—more susceptible; 
mortality rate is higher.
• Nonimmunized old dogs—highly 
susceptible to infection and disease.
Possible that humans may become subclini-
cally infected with CDV; immunization 
against measles virus also protects against 
CDV infection.
In utero infection—occurs in antibody-nega-
tive bitches; rare; may lead to abortion or to 
persistent infection; infected neonates may 
develop fatal disease by 4–6 weeks of age.
SYNONYMS
• Canine distemper.
• Hard pad disease.
SEE ALSO
Myoclonus
• CDV = canine distemper virus.
• MLV-CD = modified live virus of canine 
distemper.
https://www.uwsheltermedicine.com/library/
resources/canine-distemper-cdv
Greene CE, Vendevelde M. Canine distem-
per. In: Greene CE, ed., Infectious Diseases 
Saunders Elsevier, 2012, pp. 25–42.
Lempp C, Spitzbarth I, Puff C, et al. New 
aspects of pathogenesis of canine distemper 
leukoencephalitis. Viruses 2014, 
6:2571–2601.
Loots AK, Mitchell E, Dalton DL, et al. 
Advances in canine distemper virus 
pathogenesis research: a wildlife perspective. 
J Gen Virol 2017, 98:311–321.
Pesavento PA, Murphy BG. Common and 
emerging infectious disease in the animal 
shelter. Vet Pathol 2014, 51:478–491.
Author  Michelle C. Tensley
available onlineCanine Distemper  (continued)

Canine and Feline, Seventh Edition  213
C
Canine Infectious Diarrhea
  BASICS
• Viral, enteropathogenic bacterial, protozoal, 
or parasitic etiologies; small, large, or mixed- 
bowel diarrhea.
• Secondary systemic signs with canine 
parvovirus (CPV)-2 and salmonellosis.
• Presence of organisms on diagnostic 
screening does not indicate causation; 
patient factors (clinical signs, age, 
environmental exposure) should be 
considered before treatment.
• Some dogs will have self-resolution; 
diagnostic testing appropriate for more 
severely affected animals or if clinical signs are 
persistent having ruled out other causes of 
acute or chronic diarrhea.
• Puppies with acute diarrhea should be 
screened for CPV-2.
• Typically, fecal–oral route of infection.
• Diarrhea from enterotoxins, osmotic 
diarrhea, or invasion of epithelium resulting 
in inflammation.
• Up to 50% of dogs may have coinfections.
• Gastrointestinal (GI)—vomiting, diarrhea.
• Cardiovascular—fluid balance.
• Prevalence of most pathogens similar in 
dogs with or without diarrhea.
◦ Coronavirus more common in dogs with 
diarrhea.
◦ Dogs with diarrhea more likely to have 
>1 enteropathogen.
• Specific prevalence in dogs in United States:
◦ 0–6%—CPV-2, Salmonella spp., 
Cystoisospora spp., Dipylidum caninum, 
Campylobacter spp., C. difficile toxin A 
and B, ascarids.
◦ 7–20%—whipworms, Giardia  spp., 
Cryptosporidium , circovirus.
◦ 35–60%— C. perfringens  enterotoxin A 
or alpha toxin gene, hookworm.
• Widespread.
• Prevalence of etiologies varies by location.
• Species—dog.
• Breed predilections—none.
• Mean age and range —largely pediatric and 
young adult dogs; older animals if in high-risk 
environments.
SIGNS
• General comments—range from mild to 
severely affected.
• Historical findings—acute or chronic, small or 
large bowel diarrhea; possibly vomiting, weight loss, hyporexia; no history of dietary indiscretion.
• Physical examination findings—depends on 
etiology and severity; may include dehydration, 
poor body condition, borborygmus, flatulence, 
hematochezia, melena, visualization of worms 
on rectal exam or peri-anal, signs of sepsis or 
systemic inflammatory response syndrome 
(SIRS).
CAUSES
• Viral—coronavirus, CPV-2, circovirus.
• Bacterial— Campylobacter spp ., Clostridium 
perfringens  enterotoxin, Clostridium difficile  
toxins, Salmonella  spp.
• Parasitic— Toxocara  spp., Ancylostoma  
spp.,Toxascaris leonine, Dipyldium caninum, 
Trichuris vulpis .
• Protozoal— Giardia  spp.
• Coccidial— Cryptosporidium  spp., 
Cystoisospora  spp.
• Pediatric and young adult dogs more 
commonly affected, particularly for viral 
enteritis, Cryptosporidium  spp., roundworm 
(Toxocara  and Toxascaris ), Cystoisospora  spp., 
and Campylobacter  spp.
• Administration of antimicrobials and 
immunosuppressive drugs increase risk for 
hospital-associated colonization of C. difficile .
• Crowding and poor sanitation.
• Lack of regular parasiticide administration.
• Dogs with environmental exposure to 
livestock or wildlife for Cryptosporidium  spp., 
Campylobacter  spp., Giardia  spp.
  DIAGNOSIS
• Acute diarrhea—dietary indiscretion, foreign 
body, pancreatitis, GI neoplasia; non-GI 
diseases: hepatotoxicity, renal disease, other 
systemic diseases (commonly other clinical 
signs such as hyporexia, vomiting, icterus).
• Chronic diarrhea—chronic enteropathy 
(dietary responsive, antibiotic responsive, or 
inflammatory bowel disease), chronic 
pancreatitis, primary GI neoplasia, and 
non-GI diseases of other organs.
• Eosinophilia—possible with intestinal 
parasitism.
• Anemia and/or microcytosis—GI hemor-
rhage or iron deficiency, particularly with 
high worm burden (e.g., T. vulpis ) or GI 
mucosal shedding (e.g., CPV).
• Leukopenia—parvoviral enteritis (bacterial 
translocation or bone marrow suppression) or 
systemic salmonellosis.
• Hyponatremia and hyperkalemia with large 
bowel diarrhea— T. vulpis .
• Azotemia and electrolyte derangements 
with dehydration.• Hypoglycemia—parvoviral enteritis and 
• Panhypoproteinemia and hypocholesterol -
emia if secondary protein-losing enteropathy 
or GI blood loss.
IMAGING
• Abdominal radiographs if no response to 
symptomatic care to rule out other causes of 
diarrhea.
• Abdominal ultrasound recommended in 
nonpediatric patients with diarrhea that is 
nonresponsive to symptomatic care.
• Fecal flotation—for intestinal parasitism; 
false negatives possible (ova are intermittently 
shed); dogs suspected to have intestinal 
parasitism should have multiple fecal flotations 
performed or be treated with anthelmintics.
• Fecal cytology—bacterial morphology 
(frequent spirochetes, spores) or presence of 
fungal or protozoal organisms.
• Giardia  ELISA.
• Infectious diarrhea PCR panels detect a 
range of possible causes of diarrhea; however, 
caution should be used in interpretation of 
these assays, as a positive result does not 
necessarily indicate causation and false-
negative results are possible.
• Gross examination of intestinal mucosa 
may demonstrate parasites attached to 
intestinal mucosa with multifocal hemor-
rhagic ulcerations, submucosal congestion or 
hemorrhage, intestinal wall thickening.
• Histopathology of intestine may show 
eosinophilic, neutrophilic, or lymphoplasmacytic 
enteritis with varying degrees of hemorrhage and 
necrosis, depending on etiology.
  TREATMENT
• Mildly affected dogs—outpatient basis.
• Moderate to severely affected dogs may 
require IV administration of isotonic 
balanced electrolyte solution for dehydration.
• Electrolyte and acid-base imbalances should 
be corrected with fluid therapy and moni-
tored closely.
• Dextrose should be supplemented 
parenterally in dogs with hypoglycemia.
• Packed red blood cell or plasma transfusions 
should be given as needed for severe anemia or 
coagulopathies from sepsis (rare).
DIET
• Easily digestible diets until clinical signs 
have resolved, followed by slow transition 
(3–4 days) to maintenance diet.
• In anorexic pediatric patients, nasogastric 
tube feeding of liquid diet recommended if 
anorexia persists ≥48 hours.

214  Blackwell’s Five-Minute Veterinary Consult  
CCLIENT EDUCATION
• For most infectious organisms, environ-
mental decontamination prevents transmis-
sion to other pets/people and reinfection; 
isolation during hospitalization may be 
warranted depending on underlying cause.
• Appropriate vaccination and deworming 
schedules should be followed.
• Dogs with identified infectious causes of 
diarrhea should be isolated from other dogs if 
possible until clinical signs resolve.
Viral and parasitic enterocolitis can result in 
intussusceptions, especially in puppies.
• Many cases will self-resolve with supportive 
care and time.
• Empiric therapy pending diagnostics, if 
clinical signs persist—probiotics, or metroni-
dazole (10 mg/kg PO q12h) and fenbenda-
zole (50 mg/kg PO q24h for 5 days).
• Anthelmintics—fenbendazole (50 mg/kg 
PO q24h for 5 days), pyrantel pamoate 
(5–10 mg/kg PO for 3 days).
• Coccidiostatic—sulfadimethoxine 
(50–60 mg/kg PO q24h for 5–10 days), 
ponazuril (50 mg/kg PO once).
• Antiprotozoal drugs—fenbendazole 
(50 mg/kg PO q24h for 5 days).
• Campylobacteriosis with persistent clinical 
signs—erythromycin (10–15 mg/kg PO q8h) 
or azithromycin (5–10 mg/kg PO q24h).
• Probiotics may be of benefit for dogs with 
bacterial enteritis with acute or chronic signs; 
probiotics should be selected with evidence of 
efficacy (e.g., Visbiome®).
• Patients with systemic illness, leukope -
nia, or suspected GI mucosal barrier 
breakdown (evidenced by blood in the 
feces) should be treated with broad-spec -
trum antimicrobial agents and as indicated 
by specific etiology.
• Dogs with confirmed salmonella should 
not be treated with antibiotics unless 
systemically ill.
Metronidazole dose should be reduced in 
animals with hepatic insufficiency.POSSIBLE INTERACTIONS
• Metronidazole given at higher doses for 
giardiasis or long-term use can lead to 
vestibular signs.
• Some dogs may be sensitive to sulfa-
containing medications used for treatment of 
coccidiosis.
  FOLLOW-UP
• Case-based, may include reassessment of 
anemia, leukopenia, or electrolyte derange-
ments as appropriate.
• Persistent clinical signs after appropriate 
treatment is suggestive for alternative cause of 
diarrhea.
• Patients with recurrent clinical signs should 
be retested, particularly if environmental 
reinfection is possible (e.g., giardiasis, 
campylobacteriosis).
• Routine vaccination.
• Monthly flea/tick or heartworm preventa -
tive with combination anthelmintic therapy.
• Avoid subjecting poorly vaccinated or 
immunocompromised animals to high-traffic 
areas, including but not limited to pet supply 
stores, dog parks, or newly introduced poorly 
vaccinated pets.
• Sepsis.
• Anemia.
• Electrolyte disturbances.
• Aspiration pneumonia if concurrent 
vomiting (uncommon).
• Usually good to excellent; underlying 
immunosuppressive conditions may increase 
susceptibility to infection and worsen prognosis.
• Parvoviral enteritis carries guarded to poor 
prognosis without treatment; appropriate 
supportive care provides full recovery rates of 
90% or more.
Puppies and young dogs affected.ZOONOTIC POTENTIAL
• Giardiasis—low risk of transmission.
• Cryptosporidiosis.
• Salmonellosis.
• Campylobacter jejuni .
• Toxocara  spp. (ascarids)—visceral larval 
migrans in humans, most common in 
children.
• Ancylostoma  (hookworms)—cutaneous 
larval migrans in humans, most common in 
children.
If heavy endoparasite load, fenbendazole can 
be administered to pregnant bitches from 
14th day of gestation through to 14th day of 
lactation. If risk of infection is high, all 
puppies (and mothers) should be treated with 
appropriate anthelmintics at 2, 4, 6, and 8 
SEE ALSO
• Acute Diarrhea.
• Campylobacteriosis.
• Canine Coronavirus Infections.
• Canine Parvovirus.
• Clostridial Enterotoxicosis.
• Coccidiosis.
• Diarrhea, Chronic—Dogs.
• Giardiasis.
• Hookworms (Ancylostomiasis).
• Roundworms (Ascariasis).
• Whipworms (T richuriasis).
• CPV-2 = canine parvovirus.
syndrome.
Gookin JL. Infection, large intestine. In: 
Washabau RJ, Day MJ, eds., Canine & 
Feline Gastroenterology. St. Louis, MO: 
Saunders Elsevier, 2013, pp. 745–757.
Lappin MR. Infection, small intestine. In: 
Saunders Elsevier, 2013, pp. 683–695.
Authors  Kasey E. Mabry and T racy Hill
Consulting Editor  Amie KoenigCanine Infectious Diarrhea  (continued)

Canine and Feline, Seventh Edition  215
CCanine Infectious Respiratory Disease
  BASICS
A multifaceted disease whereby infectious disease 
and environment contribute to the genesis of 
cough and other respiratory signs in dogs.
Initiated by injury to the respiratory 
epithelium by viral infection followed by 
invasion of damaged tissue by bacterial, 
mycoplasmal, or other virulent organisms, 
resulting in further damage and clinical signs.
Respiratory—upper and lower airways can be 
involved. Multisystemic—cases that develop 
sepsis.
GENETICS
None
Most common in areas of high density with 
immunologically naïve or immunosuppressed 
patients (i.e., training kennels, shelters, 
veterinary hospitals).
Worldwide
Species
Dog
None
• Most severe in puppies 6 weeks–6 months 
old. • Can develop in dogs of all ages, partic  - 
ularly with preexisting airway disease.
None
SIGNS
• Related to the degree of respiratory tract 
damage and age of the affected dog and virulence 
of infectious organism. • Can be subclinical, 
mild, or severe with pneumonia. • Most viral, 
bacterial, and mycoplasmal agents spread rapidly 
from seemingly healthy dogs to others in the 
same environment; signs usually begin about 3–7 
days after exposure to the infecting agent(s).
• Uncomplicated—acute-onset cough in an 
otherwise healthy animal; dry and hacking, 
soft and dry, moist and hacking, or paroxysmal, 
followed by gagging, retching, and expecto -
ration of mucus; excitement, exercise, and 
pressure on the trachea induce coughing spells. 
• Complicated (severe)—inappetence to 
anorexia; cough is moist and productive; 
lethargy, difficulty breathing, hemoptysis, and 
exercise intolerance can occur.Physical Examination Findings
• Uncomplicated—cough readily induced with 
minimal tracheal pressure; lung sounds often 
normal; systemically healthy. • Complicated—
low-grade or intermittent fever (39.4–40.0 °C; 
103–104 °F); increased intensity of normal 
lung sounds, crackles or wheezes possible.
CAUSES
• Viral—canine distemper virus (CDV); canine 
adenovirus (CAV-2); canine parainfluenza 
(CPIV); canine respiratory coronavirus 
(CRCoV), canine reovirus; canine herpesvirus-1 
(CHV-1); canine influenza virus (CIV; H3N8 
or H3N2); canine bocavirus, canine hepacivirus; 
canine pneumovirus (CnPnV). • Most viral 
pathogens (except CHV and CDV) primarily 
infect epithelial and lymphoid tissue of the 
upper and lower respiratory tract; in severe 
cases, causing desquamation of the epithelium 
and aggregation of inflammatory cells in the 
lungs, leading to secondary bacterial coloni -
zation and infection; CRCoV infection leads to 
loss of cilia associated with the respiratory 
epithelium, increasing the severity and duration 
of secondary infections. • Bacterial— Bordetella 
bronchiseptica , with no other respiratory 
pathogens, produces clinical signs 
indistinguishable from those of other bacterial 
causes; Streptococcus equi  subsp. zooepidemicus  is 
associated with a particularly virulent course 
that can progress to death; Pseudomonas , 
Escherichia coli , Klebsiella , Pasteurella , 
Streptococcus , Mycoplasma , and other species 
equally likely.
• Substandard hygienic conditions and 
overcrowding—encountered in some pet 
shops, shelters, research facilities, and 
boarding and training kennels. • Coexisting 
subclinical airway disease—congenital 
anomalies; chronic bronchitis; bronchiectasis.
  DIAGNOSIS
• In systemically well dogs—parasitic 
bronchitis, irritant tracheobronchitis, airway 
foreign body, airway collapse. • In a dog with 
systemic signs—fungal or bacterial (aspiration) 
pneumonia, primary or metastatic neoplasia, 
congestive heart failure, migrating foreign 
body. • Provisional diagnosis of infectious 
tracheobronchitis is made in a dog with 
compelling clinical signs and a history of 
exposure to the implicated organisms. • See 
Cough.
• Early, mild leukopenia (5,000–6,000 cells/
dL)—can be detected; suggests viral cause. 
• Neutrophilic leukocytosis with a toxic left 
shift—frequently found with severe pneumonia.OTHER LABORATORY TESTS
Pulse oximetry and arterial blood gas analysis—
can reveal hypoxemia in pneumonia.
IMAGING
• Uncomplicated disease—radiographs: 
unremarkable; most useful for ruling out 
other differential diagnoses. • Complicated 
disease—radiographs: interstitial and 
alveolar lung pattern with a cranioventral 
distribution typical of bacterial pneumonia; 
can see diffuse interstitial lung pattern 
typical of viral pneumonia; mixed lung 
pattern can be present.
• In cases with severe disease—ideally 
perform bronchoalveolar lavage via 
bronchoscopy for cytology and microbial 
culture; tracheal wash sample acceptable, but 
increased likelihood for upper airway 
contamination. • Antimicrobial sensitivity 
pattern of cultured bacteria—identification 
aids markedly in providing an effective 
treatment plan. • PCR from bronchoalveolar 
lavage, nasal, ocular, or pharyngeal secretions 
can be used to detect virus, though there is 
difficulty in interpreting results as many 
healthy animals shed virus in the absence of 
• CPIV—causes few to no clinical signs; 
lungs of infected dogs 6–10 days after 
exposure may contain petechial hemorrhages 
that are evenly distributed over the surfaces; 
detected by immunofluorescence in 
columnar epithelial cells of the bronchi and 
bronchioles 6–10 days after aerosol 
exposure. • CAV-2—lesions confined to the 
respiratory system; large intranuclear 
inclusion bodies found in bronchial 
epithelial cells and alveolar septal cells; 
clinical signs tend to be mild and short-
lasting; lesions persist for at least a month 
after infection. • CIV (H3N8, H3N2)—
fulminant disease characterized by secondary 
Mycoplasma  or bacterial infection and 
pulmonary hemorrhage. • CRCoV—
characterized by marked inflammation of 
the trachea and nares with cilia loss in the 
former; detected by immunohistochemistry 
of the trachea or bronchioles. • Streptococcus 
equi subsp. zooepidemicus  infection—acute, 
fibrinosuppurative pneumonia with large 
numbers of cocci found within the pulmonary 
parenchyma and, often, septic thomboemboli. 
• Bordetellosis and severe bacterial 
infection—evidence of purulent bronchitis, 
tracheitis, and rhinitis with hyperemia and 
enlargement of the bronchial, mediastinal, 
and retropharyngeal lymph nodes; may see 
large numbers of Gram-positive or Gram-
negative organisms in the mucus of the 
tracheal and bronchial epithelium.

216  Blackwell’s Five-Minute Veterinary Consult  
C
  TREATMENT
• Outpatient—strongly recommended for 
uncomplicated disease. • Inpatient—strongly 
recommended for complicated disease and/or 
Fluid administration—indicated for 
complicated disease and/or pneumonia.
ACTIVITY
Enforced rest—14–21 days with uncompli-
cated disease; for at least the duration of 
radiographic evidence of pneumonia in 
severely affected dogs.
DIET
Good-quality commercial food.
• Isolate patient from other animals; infected 
dogs can transmit the agent(s) before onset of 
clinical signs and afterward until immunity 
develops. • Dogs with uncomplicated disease 
should respond to treatment in 10–14 days. 
• Once infection spreads in a kennel, it can be 
controlled by evacuation for 1–2 weeks and 
disinfection with commonly used chemicals, 
such as sodium hypochlorite (1 : 30 dilution), 
chlorhexidine, and benzalkonium.
• Amoxicillin/clavulanic acid (12.5–25 mg/kg 
PO q12h) or doxycycline (5 mg/kg PO q12h or 
10 mg/kg PO q24h)—initial treatment of 
uncomplicated disease. • Penicillin (ampicillin 
10–20 mg/kg IV q6–8h or ticarcillin 40–50 mg/
kg IV q6–8h) with aminoglycoside (gentamicin 
2–4 mg/kg IV/IM/SC q6–8h or amikacin 
6.5 mg/kg IV/IM/SC q8h) or fluoroquinolone 
(enrofloxacin 5–10 mg/kg PO/IM/IV q24h)—
usually effective for severe disease. 
• Antimicrobial therapy—continue for at least 
10 days beyond radiographic resolution. • B. 
bronchiseptica  and other resistant species—some 
antimicrobials may not reach adequate 
therapeutic concentrations in the lumen of the 
lower respiratory tract, so oral or parenteral 
administration may have limited effectiveness; 
nebulization with gentamicin (3–5 mg/kg) can 
decrease bacterial numbers when administered 
daily for 3–5 days; use in conjunction with 
systemic antibiotics in dogs with parenchymal 
disease. • Butorphanol (0.55 mg/kg PO 
q8–12h) or hydrocodone bitartrate (0.22 mg/kg 
PO q6–8h)—effective suppression of dry, 
nonproductive cough not associated with 
bacterial infection. • Bronchodilators (e.g., 
terbutaline 0.625–5 mg/dog q8–12h)—may be 
used to control bronchospasm and wheeze.CONTRAINDICATIONS
• Do not use cough suppressants in patients 
with pneumonia. • Employ glucocorticoids only 
in cases with significant inflammatory disease 
refractory to conventional supportive care.
None
Fluoroquinolones and theophylline deriva-
tives—concurrent use causes high and 
possibly toxic plasma theophylline concentra-
tion. Dose reduce theophylline while 
concurrently administering fluoroquinolones.
None
  FOLLOW-UP
• Uncomplicated disease—should resolve 
spontaneously or respond to treatment in 10–14 
days; if patient continues to cough 14 days or 
more after establishment of an adequate treat  - 
ment plan, question the diagnosis of uncompli -
cated disease. • Complicated disease—  
repeat thoracic radiography until at least 7 days 
beyond resolution of all clinical signs.
Shedding of the causative agent(s) of infectious 
respiratory disease in airway secretions of dogs 
undoubtedly accounts for the persistence of 
this problem in kennels, animal shelters, 
boarding facilities, and veterinary hospitals.
Viral and Bacterial Vaccines
• Modified live CDV and CAV-2 vaccines 
provide reliable protection and are considered 
core vaccines for all puppies; can be admin -
istered at 6 weeks of age, every 2–4 weeks. • B. 
bronchiseptica  and CPIV vaccine—can vaccinate 
puppies mucosally or intranasally as early as 2–4 
weeks of age without interference from maternal 
antibody and follow with annual revaccination; 
can vaccinate mature dogs with a one-dose 
intranasal vaccination (at the same time as their 
puppies or when they receive their annual 
vaccinations). • Inactivated B. bronchiseptica  
parenteral vaccine—administered as two doses, 
2–4 weeks apart; initial vaccination of puppies is 
recommended at or about 6–8 weeks of age; 
revaccinate at 4 months of age. • Inactivated 
CIV vaccines (H3N2 and H3N8) available to 
reduce severity and duration of clinical signs but 
considered noncore; can be administered 
starting at 6 weeks as two doses, 2–4 weeks 
apart; results in seroconversion.
N/A
• Natural course of uncomplicated disease, if 
untreated—10–14 days; simple restriction of 
exercise and prevention of excitement shortens the course. • Typical course of severe 
disease—2–6 weeks; patients that die often 
develop severe pneumonia that affects 
multiple lung lobes and multiple organ 
dysfunction due to sepsis.
May accompany other respiratory tract 
anomalies.
Most severe in puppies 6 weeks–6 months old 
and in puppies from commercial pet shops 
and humane society shelters.
Potential zoonotic risk of Streptococcus equi  
subsp. zooepidemicus  and B. bronchispetica  
reported in single case reports.
High risk in dogs on extensive medical 
treatment; especially risky for dogs in 
overcrowded breeding facilities.
SYNONYMS
• Kennel cough. • Infectious 
tracheobronchitis—uncomplicated disease.
• CAV-2 = canine adenovírus. • CDV = 
canine distemper vírus. • CHV-1 = canine 
herpesvirus-1. • CIV = canine influenza 
virus. • CnPnV = canine pneumovirus. 
• CPIV = canine parainfluenza. • CRCoV = 
canine respiratory coronavirus.
https://www.cdc.gov/flu/other/canine-flu
Bemis DA. Bordetella and Mycoplasma 
respiratory infection in dogs. Vet Clin 
North Am Small Anim Pract 1992, 
22:1173–1186.
Buonavoglia C, Martella V. Canine respira-
tory viruses. Vet Res 2007, 38(2):355–373.
Chalker VJ, Owen WM, Paterson C, et al. 
Mycoplasmas associated with canine 
infectious respiratory disease. Microbiology 
2004, 150(Pt 10):3491–3497.
Erles K, Dubovi E, Brooks HW, Brownlie J. 
Longitudinal study of viruses associated 
with canine infectious respiratory disease. J 
Clin Micro 2004, 42:4524–4529.
Priestnall SL, Mitchell JA, Walker CA, et al. 
New and emerging pathogens in canine 
infectious respiratory disease. Vet Path 
2014, 51(2):492–504.
Author  Jonathan D. Dear
available onlineCanine Infectious Respiratory Disease  (continued)

Canine and Feline, Seventh Edition  217
C
Canine Parvovirus
  BASICS
• An acute systemic illness characterized by 
vomiting, hemorrhagic enteritis, and 
• Myocardial form was observed in puppies 
in late 1970s, now rare.
• Most puppies protected against neonatal 
infection by maternal antibodies.
• Monoclonal antibodies have revealed 
antigenic changes in canine parvovirus 
(CPV)-2; CPV2a, b, and c strains have been 
• Original virus now virtually extinct in 
domestic dogs.
• CPV2c viruses are more virulent, and 
mortality rates higher.
• CPV-2 is closely related to feline panleuko -
penia virus (FPV).
• Parvoviruses require actively dividing cells 
for growth.
• After ingestion of virus there is a 2–4-day 
period of viremia.
• Early lymphatic infection is accompanied 
by lymphopenia and precedes intestinal 
infection and clinical signs.
• By postinfection (PI) day 3, rapidly dividing 
crypt cells of small intestine are infected.
• Viral shedding in feces starts ∼3–4 days PI, 
peaks with clinical signs.
• Virus ceases to be shed in detectable 
amounts by PI days 8–12.
• Absorption of bacterial endotoxins from 
damaged intestinal mucosa plays a role in 
CPV-2 disease.
• Intensity of illness related to viral dose and 
antigenic type.
• Cardiovascular—myocarditis (uncommon), 
GENETICS
Unknown
Common in breeding kennels, animal 
shelters, pet stores.
Worldwide
Species
Dog
• Certain breeds are at increased risk, 
including Rottweiler, Doberman pinscher, 
American pit bull terrier, Labrador retriever, 
German shepherd dog, and Yorkshire terrier.• Higher fatality rates are seen in hounds, 
gundogs, and nonsporting pedigree groups.
• Illness occurs at any age.
• Most severe in dogs 6–24 weeks of age.
None
SIGNS
Suspect CPV-2 infection whenever puppies 
have an enteric illness.
• Sudden onset of bloody diarrhea, anorexia, 
and vomiting.
• Some dogs may collapse in a shock-like 
state and die without enteric signs.
• In breeding kennels, several littermates may 
become ill simultaneously or within a short 
period.
• Occasionally, one or two puppies in a litter have 
minimal signs, followed by death of littermates, 
which may reflect degree of virus exposure.
• Hypovolemic shock—weak pulse, tachy  - 
cardia, dull mentation.
• Severe hemorrhagic diarrhea.
• Fluid-filled intestinal loops may be palpated.
• Dehydration, weight loss, abdominal 
• May have fever or hypothermia.
CAUSES
CPV-2.
• Unvaccinated dogs.
• Dogs <4 months of age.
• Co-pathogens such as parasites, viruses, and 
certain bacterial species (e.g., Campylobacter  
spp., Clostridium  spp.) may exacerbate illness.
• Severe, often fatal parvoviral infections have 
been demonstrated in puppies exposed 
simultaneously to CPV-2 and canine coronavirus.
  DIAGNOSIS
• Canine coronavirus infection.
• Salmonellosis; colibacillosis; other enteric 
• Gastrointestinal foreign bodies.
• Gastrointestinal parasites.
• Acute hemorrhagic diarrhea syndrome 
(previously hemorrhagic gastroenteritis).
• Intussusception (may be concurrent).
• Toxin ingestion.
• Lymphopenia—characteristic; commonly 
occurs PI days 4–6.• Severely affected dogs exhibit severe 
neutropenia with onset of intestinal damage.
• Leukocytosis during recovery.
• Serum chemistry profiles help assess 
electrolyte disturbances (especially 
hypokalemia), presence of azotemia, 
panhypoproteinemia, hypoglycemia.
• Virus antigen detection in stool at onset of 
disease and for 2–4 days afterward; many 
commercial point-of-care ELISA assays 
available, also PCR and quantitative PCR 
methodologies.
• Serologic tests are not diagnostic because 
dogs often have high titers from vaccination 
and/or maternal antibodies.
IMAGING
• Abdominal radiographs—generalized small 
intestinal ileus; exercise caution to prevent 
misdiagnosis of intestinal obstruction, but 
intussusception may cause obstructive pattern.
• Abdominal ultrasound—fluid-filled, atonic 
small and large intestines, duodenal and 
jejunal mucosal layer thinning with or 
without indistinct wall layers and irregular 
luminal-mucosal surfaces, extensive duodenal 
and/or jejunal hyperechoic mucosal speckling, 
and duodenal and/or jejunal corrugations; 
intussusceptions can be identified.
• Electron microscopy detects fecal virus 
during early stages of infection.
• Samples for virus detection should be 
submitted during acute phase of infection; 
ship specimens refrigerated, not frozen.
• Gross changes include subserosal congestion 
and hemorrhage or frank hemorrhage into 
small intestinal lumen, or intestines that are 
empty or contain yellow or blood-tinged fluid.
• Mesenteric lymph nodes often enlarged and 
edematous, with hemorrhages in cortex.
• Thymic atrophy in young dogs.
• Pulmonary edema and hydropericardium 
may be only gross change in dogs with 
myocarditis and heart failure.
• Histopathology reveals intestinal 
inflammation and necrosis, with severe villus 
atrophy.
  TREATMENT
• Symptomatic and supportive (see Acute 
Vomiting; Acute Diarrhea; Gastroenteritis, 
Acute Hemorrhagic Diarrhea Syndrome), 
including IV fluids, antibiotics, antiemetics, 
and analgesics.
• Intensity depends on severity of signs; 
both in- and outpatient treatment protocols 
exist.

218  Blackwell’s Five-Minute Veterinary Consult  
C• Goals are to provide intestinal nutrients, 
restore and maintain fluid and electrolyte 
balance, and resolve shock, sepsis, and 
endotoxemia.
• Fecal microbiota transplant may speed 
resolution of diarrhea.
• Prompt, intensive inpatient care leads to 
treatment success.
• Proper, strict isolation procedures are 
essential.
• Exercise care to prevent spread of CPV-2, a 
very stable virus.
• Antiviral drugs have not yet been shown to 
be a critical part of treatment.
• Hospitalize patients and monitor for 
dehydration and electrolyte imbalance.
• Fluids are usually supplemented with 
potassium chloride, 5% dextrose, and 
possibly sodium bicarbonate (if severe 
metabolic acidosis due to bicarbonate loss).
ACTIVITY
Restrict until symptoms abate.
DIET
Puppies receiving early enteral nutrition via a 
nasoesophageal tube (compared to puppies 
that received nothing enterally until cessation 
of vomiting) showed earlier clinical improve-
ment, significant weight gain, and improved 
gut barrier function, which could limit 
bacterial or endotoxin translocation.
• Inform about need for thorough disin -
fection, especially if other dogs are on 
premises; strict sanitation is essential; a 1 : 30 
dilution of bleach (5% sodium hypochlorite) 
destroys CPV-2 in a few minutes.
• If possible, isolate puppies until they reach 
3 months of age and vaccinate repeatedly; 
typical protocols involve vaccination at 6, 9, 
and 12 weeks of age.
• Puppies can be infected with virulent virus 
before any vaccine will confer immunity.
• CPV-2 is shed for less than 2 weeks after 
infection; no carrier state has been substan  - 
tiated.
• Exercise caution to prevent misdiagnosis of 
intestinal obstruction, especially if vomiting is 
only clinical sign.
• Intussusceptions can occur.
See Acute Vomiting; Acute Diarrhea; 
Gastroenteritis, Acute Hemorrhagic Diarrhea 
Syndrome.DRUG(S) OF CHOICE
Additional recommended drugs include 
parenteral antibiotics (ampicillin and 
gentamicin) and antiemetics (e.g., ondanse-
tron, maropitant).
Gentamicin may cause renal toxicity in 
dehydrated puppies.
  FOLLOW-UP
There is an increased incidence of discospondy -
litis in puppies that had parvovirus infection.
• Inactivated and live vaccines are available 
for prophylaxis, and vaccines differ in their 
capacity to immunize puppies with maternal 
antibodies.
• Vaccination with a modified live vaccine at 
4 weeks of age in puppies with high maternally 
derived antibody concentrations resulted in 
seroconversion rates of up to 80%; this may 
lead to a decreased window of susceptibility 
to CPV infection and might be an adjunct 
control method in contaminated 
• Control of CPV-2 requires efficacious 
vaccines, isolation of puppies, and stringent 
hygiene.
• Septicemia/endotoxemia.
• Discospondylitis.
• Prognosis is guarded in severely affected 
puppies.
• Prognosis is good for dogs that receive 
prompt initial treatment and survive initial 
crisis—approximately 80% survival rate.
• Poor prognosis if a patient is purebred, has 
a low bodyweight, and if the following 
biomarker levels are present after 24 hours of 
intensive therapy: severe persistent leuko- and 
lymphopenia, persistently elevated or rising 
serum cortisol concentration ( >8.1 μg/dL), 
severe hypothyroxinemia (<0.2  μg/dL), 
hypocholesterolemia (<100 mg/dL), and 
persistently elevated serum C-reactive protein 
(>97.3 mg/L).
• Conversely, puppies with a good prognosis 
are of mixed breed, >6 months old, and show 
the following biomarker values: total leukocyte 
count >4.5 × 103/μL, lymphocyte count >1 × 
103/μL, and mature neutrophil count >3 × 
103/μL. Additionally, a serum cortisol 
concentration <8.1  μg/dL at 48 hours after admission is associated with 96% survival, 
and a serum thyroxine concentration 
>0.2 μg/dL at 24 hours after admission is 
associated with 100% survival. An HDL-
cholesterol concentration >50.2 mg/dL at 
admission is associated with 100% survival.
Coinfection with intestinal helminths and 
Giardia  are indicative of unhygienic housing 
conditions and can worsen clinical signs and 
contribute to morbidity.
Infection less likely in dogs >1 year of age, 
but can still occur, especially if unvaccinated.
Parvovirus per se is not zoonotic, but these 
puppies may harbor coinfections with Giardia,  
which can be zoonotic.
Pregnant animals are likely to abort.
SEE ALSO
• Acute Vomiting.
Diarrhea Syndrome.
• Shock, Septic.
• FPV = feline panleukopenia virus.
• PI = postinfection.
Mohr AJ, Leisewitz AL, Jacobson LS, et al. 
Effect of early enteral nutrition on intestinal 
permeability, intestinal protein loss, and 
outcome in dogs with severe parvoviral 
enteritis. J Vet Intern Med 2003, 
17:791–798.
Schoeman JP , Goddard A, Herrtage ME. 
Serum cortisol and thyroxine concentra-
tions as predictors of death in critically ill 
puppies with parvoviral diarrhea. J Am Vet 
Med Assoc 2007, 231:1534–1539.
Venn EC, Preisner K, Boscan PL, et al. 
Evaluation of an outpatient protocol in the 
treatment of canine parvoviral enteritis. 
J Vet Emerg Crit Care 2017, 27:52–65.
Author  Johan P . Schoeman
available onlineCanine Parvovirus  (continued)

Canine and Feline, Seventh Edition  219
C
Canine Schistosomiasis (Heterobilharziasis)
  BASICS
OVERVIEW
• Heterobilharzia americanum  is a trematode 
of the genus Schistosoma that has fresh water 
lymnaeid snails as intermediate hosts and 
raccoons as the natural definitive host.
• Eggs passed in the feces of raccoons hatch 
to release miracidia that penetrate freshwater 
snail hosts. After a period of development and 
asexual multiplication, the snails release 
cercariae that infect the next host by skin 
penetration. After penetrating skin, larvae 
undergo a migration to the lung and then 
make their way to mesenteric veins, where 
separate males and females form pairs. Eggs 
laid by female worms are carried to the 
intestinal wall, where they erode their way 
through to the lumen to be passed in the 
feces. Other eggs are carried to the liver or 
other organs by the bloodstream, where they 
lodge and cause granulomatous disease.
• Dogs become infected in contact with 
freshwater containing cercariae.
• Endemic in raccoons in southeastern United 
States; canine cases reported from Arkansas, 
Indiana, Florida, Georgia, Kansas, Louisiana, 
North Carolina, Oklahoma, and Texas.
Dogs, typically adult, that have access to 
swampy areas or bayous.
SIGNS
• Lethargy (most common sign), weight loss, 
and decreased appetite.
• Other signs include vomiting, diarrhea, 
anorexia, polyuria/polydipsia; more rarely 
melena, borborygmus, ascites.
Swimming in freshwater in areas 
contaminated with cercariae from miracidia.
  DIAGNOSIS
• Bacterial diarrhea.
• Viral enteritis.
• Hepatopathies.
• CBC—anemia, lymphopenia, eosinopenia 
or eosinophilia, thrombocytopenia.
• Biochemistry—elevated liver enzyme 
activities, azotemia, hypercalcemia, hyper­
natremia, hyperglobulinemia, 
• Urinalysis—proteinuria.OTHER LABORATORY TESTS
• Elevated parathyroid hormone ­related 
protein (PTH ­rp) reported in dogs with 
hypercalcemia.
• PCR on feces (Texas A&M Gastrointestinal 
IMAGING
Contrast radiographs and ultrasound may 
reveal thickened bowel walls; calcified eggs 
disseminated into tissues may give the false 
impression of soft tissue mineralization.
• Eggs with miracidia can be identified in 
feces, but feces must be kept in saline (not 
water) or miracidia will spontaneously hatch, 
making diagnosis impossible.
• Fecal direct or sedimentation methods are 
preferred to fecal flotation; routine fecal 
flotation will not detect these heavy eggs; if 
used, requires flotation with sugar solution 
with specific gravity of 1.3.
• Histopathology—trematode eggs in 
multiple organs (especially liver, intestine, 
pancreas, lymph nodes); lymphoplasmacytic, 
histiocytic, and eosinophilic to granuloma­
tous enteritis, hepatitis with possible 
peri­portal fibrosis, dystrophic mineralization 
of multiple tissues.
  TREATMENT
Inpatient care for the first few days of treat  ­ 
ment may be warranted, as the response to 
worm kill may require supportive care.
• Praziquantel—25 mg/kg PO q8h for 2–3 days.
• Fenbendazole—50 mg/kg PO q24h for 
10 days; clinical improvement without 
parasite elimination has been reported with 
fenbendazole.
  FOLLOW-UP
• Check feces after treatment to ensure that it 
does not contain eggs.
• Reinfection from environment is possible.
In Japan and other countries with endemic 
Schistosoma japonicum , dogs can be infected 
with this human and zoonotic species.ZOONOTIC POTENTIAL
Stages in the dog pose no threat to people; 
with shared waterway exposure, cercariae can 
cause skin lesions in people.
SYNONYMS
• Schistosomiasis.
• Swimmer’s itch (human, skin penetration of 
cercariae).
• PTH ­rp = parathyroid hormone ­related 
protein.
Fabrick C, Bugbee A, Fosgate G. Clinical 
features and outcome of Heterobilharzia 
americana  infection in dogs. J Vet Intern 
Med 2010, 24:140–144.
Flowers JR, Hammerberg B, Wood SL, et al. 
Heterobilharzia americana  infection in a 
dog. J Am Vet Med Assoc 2002, 
220:193–196.
Stone RH, Frontera ­Acevedo K, Saba CF , 
et al. Lymphosarcoma associated with 
dog. J Vet Diag Invest 2011, 
23:1065–1070.

220  Blackwell’s Five-Minute Veterinary Consult  
CCar Ride Anxiety—Dogs and Cats
  BASICS
Excessive or disruptive distress, fear, or panic 
associated with vehicle travel. Anxiety 
exhibited during travel can be mistaken for 
Unknown or not definitively determined. 
Lack of car ride experience, generalized 
anxiety disorder, nausea, previous negative 
experience with car rides; fear, anxiety, or 
arousal related to visual or auditory stimuli.
• Neuromuscular.
GENETICS
May be genetic component, but experiential 
learning may be more significant.
Reported in over 50% of cats and over 20% 
of dogs.
None
Any. Young or ill animals may be predisposed 
to motion sickness.
None
SIGNS
• May include pacing, restlessness, 
inappetence, vigilance, excitability, and 
vocalization including whining or high-
pitched barking in dogs and growling, 
hissing, meowing, or yowling in cats.
• Locomotion varies between individuals—
some may pace while others remain 
immobile; fear that manifests as freezing or 
hiding may be underrecognized and 
underreported.
• Pet-related panic, vocalization, and pacing 
may impair owner’s ability to drive safely.
• T ravel-related anxiety may prevent owners 
from taking pets to destinations (e.g., 
veterinary visits, grooming, social events, 
training).
Physiologic and Physical Signs
May include panting, rapid heart rate, 
drooling, urination, vomiting, defecation.
Normal unless underlying medical problems.CAUSES & RISK FACTORS
• Behavioral causes include unruliness, 
inadequate or poor prior experience traveling; 
insufficient adaptation to carriers, leashes, or 
restraint devices; fear and reactivity to visual 
stimuli such as people, animals, bikes, or cars; 
and generalized anxiety.
• Prior stressful or uncomfortable experiences 
following car rides such as veterinary visits, 
boarding, or shelter relinquishment.
• T raumatic events such as sudden stops or 
car accidents.
• Medical conditions may exacerbate or 
manifest as anxiety—motion sickness, 
musculoskeletal pain or discomfort, dental 
disease or pain, gastrointestinal upset, sensory 
hypersensitivity.
  DIAGNOSIS
• Fear and anxiety-related behavior.
• Manifestation of pain, nausea, or physical 
• Acute onset or abrupt change in car ride 
anxiety warrants ruling out contributory 
medical conditions.
If indicated by clinical signs and prior to drug 
therapy.
If indicated by clinical signs.
IMAGING
  TREATMENT
ACTIVITY
Normal. Recommend adequate exercise and 
play before car ride.
DIET
• Normal.
• Providing highly palatable food during car 
travel may distract, reduce stress, and promote 
a positive association with car travel.
• If the pet has experienced nausea or 
vomiting in association with car travel, fasting 
is recommended.
A complete behavior program includes 
empathy, environmental management, and 
behavior modification together with supple- 
ments or medication where indicated.
Compassion
• Give thoughtful preparation and consid -
eration for the pet’s perspective before 
traveling; allow time for travel and be 
patient.• Anticipate and avoid evoking the pet’s fears 
to prevent exacerbating established fears; for 
example, when carrying a pet in a carrier, 
consider their viewpoint and the unsettling 
motion that may be experienced.
• Avoid reprimands or scolding.
• Avoid forcing pets that are unfamiliar or do 
not get along to be in close proximity.
Management and Safety
• Provide stable footing and secure resting 
locations.
• Consider crating if pet acclimated to crate 
confinement; pet seat belts, barriers, and seat 
slings can also be beneficial.
• A nondriver should accompany highly 
distressed pets.
Anxiety Reduction
• Multimodal comforting and anxiolytic 
support provides the best outcome.
• Window shades, covered crates, solid wall 
carriers, or products for dogs such as Doggles® 
or Thundercap® may alleviate anxiety related 
to visual stimuli.
• Classical music or psychoacoustically 
designed music for dogs or cats may help to 
calm; music or white noise may mute 
perception of fear-evoking sounds.
• Comforting pressure wraps may alleviate 
anxiety.
• Synthetic pheromone analogues (Adaptil®, 
Feliway®) sprayed into carriers, onto bedding, 
or on a bandana (for dogs) may reduce anxiety.
• Anxiety-reducing supplements or 
medications should be considered.
Behavior Modification
• Rehearse settle and relax positions when not 
traveling.
• Teach the dog to get in and out of the car 
by positive reinforcement (e.g., food or toy 
reward).
• Teach cats and small dogs to go in and out 
of carriers willingly; they should be acclimated 
to the motion of being in a carrier that is 
being carried.
• Practice training when travel is not imminent; 
use positive reinforcement training and avoid 
reprimand or intimidation training; animals 
should never receive corrections from shock, 
prong, or choke collars.
• During travel, provide comforting activities 
such as toys, food chews, or feeding puzzles 
that may distract the pet, reduce anxiety, or 
counter-condition the pet to car rides.
• Psychotropic medication, supplements, or 
pheromones may be beneficial or necessary

Canine and Feline, Seventh Edition  221
C
as an adjunct to the behavior program; 
short-acting anxiolytics are appropriate for 
pets traveling occasionally; administer 
anxiolytics so that optimal effect precedes 
onset of anxiety; the effect of anxiolytics 
may be overcome by severe anxiety or 
distress; high or repeated doses, extreme 
anxiety, and other medical conditions 
increase the risk for profound sedation and 
drug reactions.
• Drugs should be trial dosed in advance to 
determine effects, side effects, optimal dose, 
and duration.
• Address concurrent behavioral conditions 
(e.g., separation anxiety, fears, phobias, 
anxiety, reactivity) that may warrant 
ongoing anxiolytics (e.g., tricyclic anti -
depressants [TCAs] or selective serotonin 
reuptake inhibitors [SSRIs]) in conjunction 
with the treatment of travel-related anxiety.
• Anxiolytic; see Table 1 for drug options and 
dosing information.
• Give 30–60 minutes prior to travel.
• Side effects—incoordination, hyperphagia, 
paradoxical excitability, muscle relaxation, 
possible amnesic effect that might interfere 
with learning.
• Hyperphagia may be advantageous for pets 
with stress anorexia.
• Oxazepam and lorazepam have no active 
intermediate metabolites and may be safer 
if hepatic function compromised; injectable 
midazolam may be useful if administered 
in the veterinary hospital before home travel.
Maropitant
• May be indicated for nausea related to 
travel and prior to opioid sedation.
• Dog—1–2 mg/kg PO 2h before travel; for 
motion sickness 8 mg/kg given with a small 
amount of food 1–2h before travel.
• Cat—1 mg/kg SC daily.
Trazodone
• Dog—2–5 mg/kg; titrate up to 5–10 mg/kg 
based on effect; higher doses may be utilized 
by experienced clinicians; may be started 
twice daily 12–48h in advance.• Cat—25–50 mg/cat for car travel.
• Side effects—sedation, lethargy, 
incoordination, cardiac conduction 
Gabapentin
• Cat—20 mg/kg (50–150 mg/cat) 2–3h 
before travel.
• Dog—10–30 mg/kg PRN to BID; may be 
started twice daily 12–48h in advance.
• Side effects—sedation, ataxia.
Clonidine
• Dog—0.01–0.05 mg/kg PO; begin at low 
dose and titrate to most effective dose; 
maximum effect may take up to 2h with 
faster absorption on an empty stomach; may 
be started twice daily 12–48h in advance.
• Side effects—transient hyperglycemia, 
bradycardia, agitation; use with caution in 
cardiac disease or compromised renal or liver 
function.
Dexmedetomidine Oromucosal Gel
• Dogs—125  μg/m2 onto oral mucosa 30–60 
min prior to travel; can be repeated in 2h.
• Licensed for use in dogs with noise aversion.
• Side effects—sedation, paradoxical excite -
ment, pale mucous membranes, emesis.
Acepromazine
• Dog and cat—0.5–2.2 mg/kg PO.
• Not for sole use; may be combined with 
anxiolytic medication for added sedation.
• Side effects—ataxia, inhibits thermoregulation, 
peripheral vasodilation, muscle tremor or 
spasm, altered noise reactivity.
Pheromone
F3 cheek gland pheromone or dog-appeasing 
pheromone given 30–60 min before travel.
Natural Supplements
• For mild to moderate anxiety or adjunctive 
therapy—alpha-casosopene alone or in a diet 
in combination with l-tryptophan; l-theanine 
alone or in combination products containing 
whey protein, Phellodendron amurense , and 
Magnolia officinalis ; melatonin; Souroubea  
and Plantanus ; or a calming probiotic 
supplement.• Lavender essential oils may have a calming 
effect in dogs, but avoid in cats since floral 
scents may be aversive.
Avoid use or use with caution in combination 
with any drug that enhances serotonin 
transmission (e.g., trazodone, SSRIs, TCAs) 
and that may pose an increased risk for 
All listed medications are extra-label or off-label 
(except maropitant). Use with informed consent.
  FOLLOW-UP
Ask about travel-related distress as part of 
wellness assessment, and recommend early 
intervention and prevention. T ravel-related 
difficulties pose a barrier for bringing pets to 
the veterinary hospital.
• Provide preventive guidance on making 
travel positive and carrier training at first 
puppy or kitten visit.
• Avoid travel for severely affected pets.
• Use appropriate medication when travel 
required.
Likely to worsen if untreated.
• Generalized anxiety disorder, noise-related 
fears and phobias, separation anxiety; hyper  - 
attac hment.
• Dental disease or pain.
Cognitive decline may exacerbate anxiety.Table 1  
Benzodiazepine doses
Canine Feline
Alprazolam 0.02–0.1 mg/kg PO q6–12h 0.025–0.1 mg/kg PO q8–24h
Clonazepam 0.1–1.0 mg/kg PO q8–12h 0.02–0.2 mg/kg PO q12–24h
Diazepam 0.5–2 mg/kg PO PRN (e.g., q6h)
Lorazepam 0.025–0.2 mg/kg PO q24h to PRN 0.025–0.05 mg/kg PO 12–24h
Oxazepam 0.2–1 mg/kg PO q12–24h 0.2–0.5 mg/kg PO 12–24h(continued)  Car Ride Anxiety—Dogs and Cats

222  Blackwell’s Five-Minute Veterinary Consult  
CZOONOTIC POTENTIAL
A distressed pet may cause distraction and put 
drivers at risk for accidents.
Drug use in breeding, pregnant, or lactating 
animals should be avoided.
SEE ALSO
• Fear and Aggression in Veterinary 
Visits—Cats.
Visits—Dogs.• Fears, Phobias, and Anxieties—Cats.
www.catalystcouncil.org/resources/video
Crowell-Davis SL, Murray T, Dantas L. 
Hoboken, NJ: Wiley, 2019.Horwitz D, ed. Blackwell’s 5 Minute Consult 
Behavior, 2nd ed. Hoboken, NJ: Wiley, 
2018, pp. 873–884.
Author  Theresa L. DePorter
Consulting Editor  Gary M. LandsbergCar Ride Anxiety—Dogs and Cats  (continued)

Canine and Feline, Seventh Edition  223
C
Carbon Monoxide Toxicosis
  BASICS
OVERVIEW
• Carbon monoxide (CO)—odorless, 
colorless, nonirritating gas produced by 
inefficient combustion of carbon fuels.
• Common sources are fires, automotive 
exhaust, leaking coal, oil, or natural gas/
propane furnaces, gas appliances or fireplaces, 
and some paint strippers and sprays.
• CO is absorbed into the blood, forming 
carboxyhemoglobin (COHb).
• Affinity of CO for hemoglobin is approx­
imately 240 times that of oxygen.
• COHb cannot bind oxygen and impairs 
oxyhemoglobin from releasing oxygen to the 
tissues.
• Major effect is acute cellular hypoxia, 
leading to death.
• Survivors may have cardiac damage, acute 
and delayed neurotoxicity.
• Lethal concentration is approximately 
1,000 ppm (0.1%) for 1 hour.
Dogs and cats equally affected.
SIGNS
Acute Exposure
• Acute signs progress within minutes to hours.
• Neurologic signs—lethargy or agitation, 
weakness, ataxia, depressed mentation, 
deafness, coma, seizures.
• Respiratory—tachypnea and dyspnea.
• Cardiovascular—tachycardia, dysrhythmias, 
• Hyperemic skin and mucous membranes 
are rarely apparent in animals.
Chronic Exposure
• Nausea, vomiting, decreased activity, and 
cough; may mimic other diseases.
• Disturbance of postural and position 
reflexes and gait.
• Housed in areas with blocked exhaust vents, 
furnaces, appliances, or chimneys; exposure to 
automobile exhaust or kerosene heaters in 
closed spaces with poor ventilation.
• T rapped in house or kennel fires.
• Animals with impaired cardiac or 
pulmonary function.
  DIAGNOSIS
• Sedatives, ethanol, ethylene glycol, 
petroleum hydrocarbons, lead poisoning; 
cyanide or hydrogen sulfide gas toxicosis.• Smoke inhalation, primary neurologic 
disease, and severe metabolic disease.
Biochemistry—may see liver and kidney value 
elevations secondary to hypoxia.
• Carboxyhemoglobin can be measured via 
co­oximetry; may return to normal within 
hours after removal from CO source. 
Available at human hospital or veterinary 
specialty/diagnostic lab.
• Blood gas—metabolic acidosis due to lactic 
acidosis; arterial blood gas may have normal 
partial pressure of oxygen (PaO2).
IMAGING
Thoracic radiographs—evaluate for 
pulmonary injury and rule out other causes of 
respiratory signs.
• Pulse oximetry may overestimate hemo­
globin saturation (SpO2); COHb and 
oxyhemoglobin absorb light at the same 
wavelength.
• ECG—sinus tachycardia or cardiac 
dysrhythmia, ST ­T depression with myocardial 
hypoxia/anoxia.
• Blood pressure—hypotension common in 
shock.
  TREATMENT
• Supplemental oxygen (flow ­by, mask, nasal, 
oxygen cage, or intubation ± mechanical 
ventilation)—improves oxygen delivery to 
vital organs, especially brain and heart; 
decreases half ­life of COHb.
• Hyperbaric oxygen therapy use is 
controversial and not readily available in 
veterinary medicine, but will further reduce 
half­life of COHb.
• IV fluid therapy for hydration and 
perfusion and to correct metabolic acidosis.
• Sedatives and anxiolytics may be needed to 
allow oxygen supplementation—diazepam 
0.1–0.5 mg/kg IV q6–8h.
• Short ­acting opioids such as fentanyl 
(2–5  μg/kg IV followed by CRI 2–5  μg/kg/h) 
can be used for pain and sedation.
Limit 100% oxygen to <24 hours to avoid 
oxygen toxicosis.  FOLLOW-UP
• Patient monitoring—neurologic status, BP 
and ECG during hospitalization; frequency 
depends on stability of patient.
• Possible complications—delayed neurologic 
signs within days to weeks of initial improvement; 
deafness may occur/persist in survivors.
• Expected course and prognosis—respond 
and improve rapidly to oxygen therapy 
(within 30–60 minutes); prognosis guarded 
to poor with persistent or worsening respira  ­ 
tory and neurologic signs.
• Prevention—use adequate ventilation with 
use of kerosene heaters in kennels and use 
CO detectors.
Animals in house fires may have dermal burns, 
thermal and smoke inhalation injury to the 
airways, corneal ulcerations, or other injuries.
People and other pets in the same 
CO­contaminated environment are at risk.
CO reduces oxygen ­carrying ability of 
maternal blood, producing fetal hypoxia, 
abortion, or neurologic impairment of the 
fetus, often with minimal effects on the dam.
• COHb = carboxyhemoglobin.
• PaO2 = partial pressure of oxygen.
• SpO2 = oxygen saturation.
Berent AC, Todd J, Sergeeff J, et al. Carbon 
monoxide toxicity: a case series. J Vet Emerg 
Crit Care 2005, 15(2):128–135.
Fitzgerald KT. Carbon monoxide. In: 
Peterson ME, Talcott PA, eds. Small Animal 
Toxicology, 3rd ed. St. Louis, MO: Elsevier 
Saunders, 2013, pp. 479–487.
Vaughn L, Beckel N. Severe burn injury, burn 
shock, and smoke inhalation injury in small 
animals. Part 1: Burn classification and 
pathophysiology. J Vet Emerg Crit Care 
2012, 22(2):179–186.
Vaughn L, Beckel N, Walters P . Severe burn 
injury, burn shock, and smoke inhalation 
injury in small animals. Part 2: Diagnosis, 
therapy, complications, and prognosis. J Vet 
Emerg Crit Care 2012, 22(2):187–200.
Gary D. Osweiler.

224  Blackwell’s Five-Minute Veterinary Consult  
CCarcinoid and Carcinoid Syndrome
  BASICS
OVERVIEW
• Carcinoid tumors are neuroendocrine 
tumors arising from amine precursor uptake 
and decarboxylation (APUD) cells.
• Carcinoids originate from enterochromaffin 
and enterochromaffin-like cells of the gastro  - 
intestinal tract, but can be found in the liver, 
gall bladder, pancreas, tracheobronchial tree 
and genitourinary system due to embryologic 
origins.
• Carcinoids may secrete amines such as 
histamine, serotonin, prostaglandin, and 
peptides such as bradykinins and tachykinins.
• In humans, secretion causes “carcinoid 
syndrome.” This occurs in approximately 
5–10% of patients with metastatic carcinoid 
tumors. Hepatic degradation of excess 
amines, notably seratonin, is bypassed, 
causing clinical signs. Human carcinoid 
syndrome is characterized by flushing, 
abdominal pain, diarrhea, bronchospasm, and 
cyanosis. This syndrome has not been 
reported in small animals, although a recent 
report describes a dog with episodic collapse 
and melena and an ileocecal carcinoid.
• Morbidity and mortality are more often a 
function of tumor size and gastrointestinal 
blockage.
• Primary carcinoid tumors in dogs have been 
reported in the stomach, small intestine, 
colon, lung, gallbladder, and liver. In cats, 
carcinoids have been found in the stomach, 
small intestine, liver, and heart.
• Dog—rare, generally >8–9 years of age.
• Cat—rare, generally >7–8 years of age.
SIGNS
Clinical signs depend on the location of the 
primary tumor or metastases and may include 
anorexia, vomiting, dyschezia, melena, 
collapse, ascites, weight loss, and signs of 
hepatic failure or gall bladder obstruction.
  DIAGNOSIS
Differentials include primary gastrointestinal 
diseases—neoplasia, infection, inflammation, 
parasites, foreign body, dietary indiscretion, 
or hepatic/biliary disease.
• Normal, possible mild nonregenerative 
anemia.
• Electrolyte abnormalities, elevated liver 
enzyme activities, and hyperbilirubinemia can 
be present.OTHER LABORATORY TESTS
• Serum serotonin, serum chromogranin A, 
and urinary 5-hydroxyindoleacetic acid are 
measured in humans suspected of carcinoid 
tumors; these tests are more diagnostic than 
direct measurement of serum amine and 
peptides.
• Serum serotonin levels were found to be 
increased tenfold in a dog with an intestinal 
carcinoid; other testing has not been docu -
mented in animals with carcinoid tumors.
IMAGING
• Radiography and ultrasound can identify 
primary tumors and metastases.
• CT scan and MRI may also be useful.
• In humans, more sensitive molecular 
imaging includes radiolabeled somatostatin 
receptor scintigraphy (OctreoScan); radioio-
dinated metaiodobenzylguanidine (MIBG) 
imaging; and PET scans.
• Biopsy often confirms diagnosis.
• If histopathologic results are equivocal, 
electron microscopy and/or immunohisto-
chemistry (looking for chromogranin A and/
or synaptophysin expression) may be used to 
confirm a carcinoid tumor.
T umors have a fine fibrovascular stroma with 
minimal to moderate cellular pleomorphism. 
Cytoplasm is eosinophilic and usually contains 
secretory granules that stain argyrophilic and/
or argentaffin-positive (silver stains).
  TREATMENT
In some cases, surgical excision can be 
curative, especially if no metastasis. Debulking 
can decrease hormone secretion in humans, 
and it may relieve tumor-related gastrointesti-
nal obstruction.
• Octreotide, a somatostatin analogue that 
inhibits hormone secretion from the tumor 
cells, is used in humans for palliative therapy; 
as carcinoid syndrome has not been reliably 
reported in animals with carcinoid tumors, 
octreotide may be of little benefit.
• High-dose radioiodinated MIBG is used in 
humans with nonresectable or metastatic 
carcinoid.
• Interferons have demonstrated limited 
success in humans with carcinoid tumors.
• Chemotherapy and radiotherapy have 
minimal efficacy in humans with carcinoid 
tumors.• Adjuvant carboplatin therapy has been 
reported in a dog with a completely excised 
nonmetastatic jejunal carcinoid.
  FOLLOW-UP
Abdominal ultrasound and thoracic radio-
graphs should be performed regularly to 
identify metastasis.
• Limited survival data exists (few reported 
cases).
• Survival of 18 months seen in dog with 
intestinal carcinoid treated with surgery and 
carboplatin.
• Survival of 12 months reported in cats with 
extrahepatic carcinoids.
• MIBG = metaiodobenzylguanidine.
https://www.carcinoid.com
Corrigan A, Bechtel S. APUDomas: 
diagnosis, supportive care, and definitive 
treatment. Proceedings of the American 
College of Veterinary Internal Medicine 
Forum, Indianapolis, Indiana, 2015.
Rossmeisl JH Jr., Forrester SD, Robertson JL, 
Cook WT. Chronic vomiting associated 
with a gastric carcinoid in a cat. J Am Anim 
Hosp Assoc 2002, 38(1):61–66.
Author  Virginia L. Gill

Canine and Feline, Seventh Edition  225
C
Cardiac Glycoside Plant Toxicosis
  BASICS
OVERVIEW
• Same toxic profile as digoxin, in particular 
cardiovascular (CV) and gastrointestinal (GI) 
signs.
• All plant parts, fresh or dry, are considered 
toxic, but the concentration varies depending 
on specific plant and plant part.
• Plants are best identified by scientific name.
• Common plants include Adenium obesum  
(desert rose); Apocynum cannabinum  (dogbane); 
Asclepias  spp. (milkweed); Calatropis  spp. 
(giant milkweed); Convallaria majalis  (lily of 
the valley); Digitalis lanata  (wooly foxglove); 
Digitalis purpurea  (common or purple 
foxglove); Kalanchoe  spp. (mother of millions); 
Nerium oleander  (oleander); Ornithogalum 
umbellatum  (star of Bethlehem); Thevetia 
peruviana  (yellow oleander).
• Cats are more sensitive to some of the plant 
toxins than dogs.
• Dogs with the ABCB1-1 Δ gene mutation 
may be more sensitive to toxins.
SIGNS
• CV—bradycardia (rarely tachycardia), 
atrioventricular (AV) block, all forms of 
arrhythmias, death from asystole.
• GI (most frequent)—hypersalivation, 
vomiting ± blood, diarrhea ± blood.
• Neuromuscular—coma, tremors, seizures 
(rarely); may be related to decreased cardiac 
output.
• Cardiac glycoside–containing plants inhibit 
the ATPase sodium/potassium pump, 
resulting in an increase in intracellular sodium 
and a decrease in intracellular potassium; 
increased intracellular (myocyte) calcium 
results in increased cardiac contractions.
• Animals with a prior history of cardiac or 
renal disease and receiving digoxin or other 
cardiac glycoside drugs are at risk.
  DIAGNOSIS
• Beta blocker or calcium channel blocker 
toxicosis.
• Cardiac disease in general.
• Digoxin/digitoxin toxicosis.
• Ingestion of medications with known 
cardiac effects.
• Ingestion of other plants with known 
cardiac effects such as T axus  spp. (yew), 
Rhododendron  spp. (azalea, rhododendron), 
Kalmia  spp. (mountain laurel, lambkill), and 
Pieris japonica  (Japanese pieris).CBC/BIOCHEMISTRY/URINALYSIS
Serum chemistry—hyperkalemia early and 
severe, may switch to hypokalemia.
Serum digoxin levels may be useful in some 
ingestions.
• Presence of plant pieces in vomit or stool.
• ECG monitoring for cardiac arrhythmias.
Sudden death is common. Plant pieces are 
often found in the stomach and small 
intestine. Clotted blood may be present in the 
ventricles with a mottled appearance to the 
epicardium. Histopathology findings are 
similar to digoxin toxicosis.
  TREATMENT
• Emesis quickly after ingestion .
• Activated charcoal (1–2 g/kg ) with a 
cathartic × 1, followed by activated charcoal 
without a cathartic every 6–8 hours × 2 doses.
• Asymptomatic animals—hospitalize and 
monitor for 12 hours.
• Symptomatic animals—hospitalize and 
monitor with an ECG for 24 hours; administer 
appropriate IV fluids (dependent on serum 
potassium) to maintain blood pressure but not 
overload the CV system; monitor blood pressure 
closely, as hypotension may be persistent.
• Digoxin-specific fragment antigen binding 
(Fab; Digibind®) may be useful in some cases, 
especially oleander toxicosis.
• Antiemetics if vomiting is severe or persistent—
maropitant 1 mg/kg SC/IV/PO q24h in dogs 
and cats; ondansetron 0.5–1 mg/kg IV, SC, PO 
q8–12h in dogs and cats.
• Bradycardia—atropine 0.02–0.04 mg/kg 
IV/IM/SC in dogs and cats; repeat q4–6h as 
needed.
• Antiarrhythmics may be necessary in 
patients with ventricular dysrhythmias, 
evidence of poor perfusion, or who remain 
tachycardic despite IV fluid therapy—
lidocaine: dogs, 2–4 mg/kg IV to effect.
• GI protectants as needed—H2 blockers 
such as famotidine (0.5–1 mg/kg PO/SC/IM/
IV q12h); omeprazole (0.5 mg/kg PO daily); 
or sucralfate (0.25–1 g PO q8h).
Beta blockers and calcium channel blockers 
may have an additive effect on AV conduc-
tion and cause complete heart block.  FOLLOW-UP
• ECG and blood pressure monitoring for 
first 24 hours, then PRN.
• Strict attention to serum electrolytes.
• Identify and recognize plants.
• Oleander grows seemingly everywhere in 
parts of the SW United States and off-leash 
dogs and cats should be monitored closely.
Sudden death.
• Good nursing care for 5–7 days.
• Prognosis is good with early and 
appropriate care.
• Cardiac arrhythmias prolong treatment and 
hospitalization.
• Fab = fragment antigen binding.
• http://www.petpoisonhelpline.com/poisons
• http://www.aspca.org/pet-care/animal-
poison-control/toxic-and-non-toxic-plants
Eucher J. Cardiac glycosides. In: Hovda LR, 
Brutlag A, Poppenga RH, Peterson K, eds. 
Clinical Companion: Small Animal 
2016, pp. 760–769.
available online

226  Blackwell’s Five-Minute Veterinary Consult  
CCardiomyopathy, Arrhythmogenic Right Ventricular—Cats
  BASICS
OVERVIEW
Arrhythmogenic right ventricular cardiomyopathy 
(ARVC) is a rare primary cardiomyopathy 
characterized by progressive atrophy of the right 
ventricular (RV) and/or right atrial (RA) 
myocardium, with replacement by fatty or 
fibrofatty tissue that may act as an arrhythmogenic 
substrate. The condition in cats typically manifests 
as signs of right-sided congestive heart failure 
(CHF) due to progressive RV dysfunction. A 
variety of arrhythmias have been observed in cats 
with ARVC; however, sudden death does not 
appear to be well recognized in this species.
• Cats.
• One study reported mean age at present -
ation of 7.3 years (range: 1–20 years).
• Breed or sex predilections unknown.
SIGNS
Compared to dogs and humans, sudden death 
does not appear to be as well recognized in cats 
with ARVC, despite the wide variety of 
arrhythmias documented with this condition.
• Dyspnea.
• Abdominal distention may be noted.
• Signs consistent with right-sided CHF .
• Dyspnea.
• Jugular venous distention.
• Ascites.
• Heart and/or lung sounds may be muffled.
• Weak femoral pulses.
• Hepatosplenomegaly.
• Thoracic percussion may reveal presence of 
• May auscult arrhythmia.
• Unknown.
• A genetic mutation in the striatin (desmosomal 
protein) gene is associated with ARVC in some 
dogs. Genetic mutations are identified in approx  - 
imately 60% of humans with ARVC, with 
mutations identified in at least 13 genes. Genetic 
studies in feline ARVC are lacking.
  DIAGNOSIS
Uhl’s anomaly—a congenital abnormality 
characterized by partial or complete absence of myocardium in the RV free wall. 
Histopathology is required to distinguish 
this from ARVC and demonstrates 
apposing endocardial and epicardial 
surfaces, without any interposed adipose 
tissue or any evidence of inflammation or 
necrosis.
Alanine aminotransferase may be elevated 
secondary to hepatic congestion.
IMAGING
• Cardiomegaly, typically in regions of right 
atrium and right ventricle; left atrial enlarge  - 
ment may also be noted.
• Pleural effusion.
• Ascites.
• Pericardial effusion.
• Caudal vena caval dilation.
• Severe RA and RV dilation.
• RV systolic dysfunction/hypoknesis.
• T ricuspid regurgitation.
• Paradoxical septal motion.
• Focal aneurysms may be observed in the 
RV wall, often toward the apex.
• Left atrial enlargement sometimes seen.
ECG
• A variety of various arrhythmias have been 
observed in cats with ARVC.
• Ventricular premature complexes (right-
sided or left-sided in origin).
• Ventricular tachycardia.
• Supraventricular tachycardia.
• Ventricular premature complexes.
• Right bundle branch block.
• First-degree atrioventricular block.
• Third-degree atrioventricular block.
• RA and RV enlargement (tall P wave, deep 
S waves in lead II), right axis deviation.
Paracentesis and Fluid Analysis
Fluid analysis of pleural or abdominal 
effusions typically reveals modified transudate 
consistent with right-sided CHF .
• Moderate-to-severe RA and RV dilation.
• Severe thinning of RA and RV walls, which 
are easily trans-illuminated.
• Left atrial dilation and rarely left ventricular 
dilation may be seen in some cats.
• Thrombi sometimes identified.
• RV myocardial atrophy with replacement 
by fatty or fibrofatty tissue.
• Fibrosis may also be observed in right 
atrium, left ventricular free wall, and 
interventricular septum.• Focal or multifocal myocarditis.
• Apoptotic cardiomyocytes.
  TREATMENT
• Medical management of right-sided CHF is 
the mainstay of treatment for clinically 
affected cats with ARVC.
• Anti-arrhythmic therapy is not routinely 
required, but in cases with hemodynamically 
significant arrhythmias, anti-arrhythmic drugs 
should be selected based on the suspected 
underlying mechanism of the arrhythmia.
See Congestive Heart Failure, Right-Sided.
  FOLLOW-UP
Recheck when decompensation or other 
clinical signs develop.
Prognosis appears to be very poor in cats 
identified with ARVC. Reported median 
survival time after development of clinical 
signs of approximately 1 month (range: 
2 days to 4 months). Most cats die or are 
euthanized due to signs of right-sided 
CHF or thromboembolic complications.
SEE ALSO
• Cardiomyopathy, Arrhythmogenic Right 
Ventricular—Dogs.
• ARVC = arrhythmogenic right ventricular 
• RV = right ventricular.
Fox P , Maron B, Basso C, et al. 
Spontaneously occurring arrhythmogenic 
right ventricular cardiomyopathy in the 
domestic cat: a new animal model similar 
to the human disease. Circulation 2000, 
102(15):1863–1870.

Canine and Feline, Seventh Edition  227
C
Cardiomyopathy, Arrhythmogenic Right Ventricular—Dogs
  BASICS
OVERVIEW
A myocardial disease commonly character ­
ized by ventricular tachyarrhythmias that can 
be accompanied by syncope or sudden death. 
A small percentage (<5%) develop congestive 
heart failure with systolic dysfunction, 
comparable to the dilated cardiomyopathy 
observed in other breeds.
• Dog.
• Specific to the boxer, although a similar 
presentation is infrequently observed in the 
English bulldog.
• Usually observed in mature dogs between 
5 and 8 years of age. Dogs as young as 6 months 
have been reported and some affected dogs may 
not develop clinical signs until >10 years of age.
SIGNS
• Usually one of three presentations:
◦ Asymptomatic dog with ventricular 
premature complexes (VPCs) detected on 
routine examination.
◦ Syncope with VPCs detected on ECG or 
Holter monitor.
◦ Signs of left heart failure (e.g., tachypnea, 
coughing) or biventricular failure (e.g., 
ascites, tachypnea, coughing) with VPCs; 
this presentation is least common.
• Sudden death may occur before develop­
ment of obvious clinical signs.
• Adult onset, inherited (autosomal dominant).
• A genetic mutation (deletion) in a cardiac 
desmosomal gene (striatin) is associated with the 
development of the disease. Dogs that are 
homozygous for the striatin deletion appear to be 
more likely to be more severely affected with a 
higher number of VPCs, and are more likely to 
have cardiac dilation and myocardial dysfunction. 
Sudden death is more common. It is not yet 
known if this is the only genetic cause or if 
additional genetic mutations will be identified.
• At least one family of boxers with VPCs, 
ventricular dilation, and systolic dysfunction 
was found to have decreased myocardial 
l­carnitine levels and demonstrated some 
clinical improvement when supplemented 
with l ­carnitine. The cause and effect of this 
relationship is unclear, and response to this 
supplementation does not occur in all dogs 
with myocardial dysfunction.
  DIAGNOSIS
• Aortic stenosis—moderate and severe forms 
can be associated with VPCs.• Uncommon forms of acquired cardiac 
disease (neoplasia, endocarditis).
• Abdominal disease (especially splenic 
disease) can be associated with VPCs.
• Echocardiography and abdominal 
ultrasonography can be used to differentiate 
other causes of cardiac and abdominal disease.
• Genetic testing can now be performed to 
screen for the genetic mutation (https://cvm.
ncsu.edu/genetics) associated with arrhythmo­
genic right ventricular cardiomyopathy. 
Submission samples can be either a blood 
sample in an EDTA tube or a buccal swab of 
the oral mucosal surface.
• Plasma l ­carnitine levels may be evaluated 
in boxers with ventricular dilation and systolic 
dysfunction. However, plasma levels are not 
always reflective of myocardial levels. If 
plasma levels are not low, it is still possible to 
have low myocardial levels, and 
supplementation with l ­carnitine might be 
considered.
IMAGING
• Normal in most affected dogs.
• Dogs with ventricular dilation and systolic 
dysfunction may have cardiac enlargement 
and evidence of heart failure (e.g., pulmonary 
edema).
• A small percentage of dogs have ventricular 
dilation and systolic dysfunction, particularly 
if they are homozygous for the deletion 
mutation.
ECG
• Many dogs will not have VPCs on an ECG 
of brief duration since the arrhythmia can be 
intermittent. However, some dogs will have 
one or more upright VPCs on a brief lead 
II ECG.
• In either case, if suspicion of disease is 
present, Holter monitoring is recommended 
to determine the severity and complexity of 
the arrhythmia and to have a baseline for 
comparison once treatment is started. If 
Holter monitoring is not available and the 
dog is symptomatic with upright VPCs on an 
ECG, therapy should be considered.
• Gross pathology is nonspecific in most 
cases. In a small percentage of cases, left 
and right ventricular dilation may be 
observed.
• Histopathologic abnormalities include 
a fatty and fibrous infiltrate into the 
right ventricular (and sometimes interven­
tricular and left ventricular) free wall.  TREATMENT
• The goals of therapy include reduction of 
the number of VPCs, reduction of clinical 
signs, and reduction of the risk of sudden 
cardiac death. Unfortunately, there is no 
evidence that therapy can reduce the risk of 
sudden death. The decision to start therapy in 
the asymptomatic boxer with VPCs is 
controversial, since all antiarrhythmics have 
the potential to make the arrhythmia worse. 
However, dogs with as few as 300 VPCs/24 
hours have been observed to die suddenly. In 
general, initiate antiarrhythmic drugs if there 
are >1,000 VPCs/24 hours and/or significant 
runs of ventricular tachycardia or other signs 
of arrhythmia complexity (e.g., bigeminy, 
couplets), or clinical signs (syncope, exercise 
intolerance) related to the VPCs.
• Syncope and sudden cardiac death may be 
more frequently associated with stress and 
excitement. Reduce stress and effort when 
possible. There is no direct relationship 
between exercise restriction and survivability. 
Some dogs die while asleep. Thus, strict 
exercise restriction is not recommended.
• The two best choices for treating the 
ventricular arrhythmia are sotalol (1.5–
2.0 mg/kg PO q12h) or mexiletine (5–6 mg/kg 
PO q8h). Some cases continue to have 
significant ventricular ectopy after treatment 
with one of these; such cases seem to respond 
well to the combination of sotalol and 
mexiletine. These drugs have different 
mechanisms and appear to work in a safe and 
complementary fashion.
• In dogs with systolic dysfunction and heart 
failure, consider treatment with furosemide, 
enalapril, pimobendan, spironolactone, and 
l­carnitine.
Any antiarrhythmic drug has the potential to 
make an arrhythmia worse.
  FOLLOW-UP
• If possible, repeat the Holter monitor 2–3 
weeks after starting therapy to evaluate for a 
response. Affected dogs can have an 85% 
day­to­day variability in VPC number before 
medications; therefore, a good response to 
therapy would be an 85% reduction in VPC 
number. It is also anticipated that the 
complexity of the arrhythmia (bigeminy,

228  Blackwell’s Five-Minute Veterinary Consult  
Ctrigeminy, couplets, triplets, runs of 
ventricular tachycardia) will be reduced once 
on therapy. It may not always be possible to 
achieve an 85% reduction in VPC number; 
in those cases an improvement in arrhythmia 
complexity and clinical signs would be 
reasonable goals.
• Annual Holter monitoring and echocardio­
graphy are suggested, since in some cases the 
disease can be progressive.
• Advise owners that dogs are always at risk 
of sudden death. However, the majority of 
affected dogs can be maintained on antiarrhy­thmics for years with good quality of life. 
Dogs with systolic dysfunction and dilation 
have the worst prognosis, although some of 
these dogs do show improvement and a 
decreased rate of progression on l ­carnitine 
supplementation.
SYNONYMS
Boxer cardiomyopathy.SEE ALSO
• Ventricular Premature Complexes.
• Ventricular Tachycardia.
• VPC = ventricular premature complex.
Author  Kathryn M. Meurs
Consulting Editor  Michael AherneCardiomyopathy, Arrhythmogenic Right Ventricular—Dogs  (continued)

Canine and Feline, Seventh Edition  229
C
Cardiomyopathy, Dilated—Cats
  BASICS
• Dilated cardiomyopathy (DCM) is a disease 
of the heart muscle characterized by systolic 
myocardial failure and a dilated, volume-
overloaded heart that leads to signs of congestive 
heart failure (CHF) or low cardiac output.
• Before 1987, DCM was the second most 
commonly diagnosed heart disease in cats. 
Most cats had a secondary DCM as a result of 
taurine deficiency. Primary idiopathic DCM 
is now an uncommon cause of heart disease 
in cats.
• Histopathologically, the myocardium of 
cats with idiopathic DCM has evidence of 
myocytolysis, fibrosis, myofibril fragmen -
tation, and vacuolization. Gross examination 
reveals global eccentric enlargement of all 
four cardiac chambers.
• These anatomic changes are associated with 
progressive myocardial systolic failure, decreased 
contractility, decreased compliance, and 
secondary mitral valve regurgitation due to 
mitral valve annular dilation. These changes are 
typically identified by echocardiography.
• Eventually, the chronic myocardial 
dysfunction leads to CHF and clinical signs.
• Cardiovascular—DCM is a primary 
myocardial disease and primarily affects the 
heart and its ability to maintain an adequate 
cardiac output to maintain the body’s needs.
• Musculoskeletal—cats with DCM can 
present with aortic thromboembolism (ATE), 
which causes acute paraparesis or monoparesis.
• Renal/urologic—cats with DCM and CHF 
often have poor renal perfusion and 
commonly have prerenal azotemia.
• Respiratory—cats usually present with 
tachypnea or dyspnea due to CHF with 
DCM. These cats can develop both 
pulmonary edema and pleural effusion.
GENETICS
Because of the human experience with DCM, 
it is likely that feline DCM also has a genetic 
basis, either inherited or de novo, as the cause 
of the disease. No definitive mutation has 
been identified in the cat to date; however, a 
quantitative genetic evaluation of a large 
cattery suggested an inherited factor in the 
development of DCM.
Idiopathic feline DCM is relatively uncommon 
now that taurine is adequately supplemented 
in cat foods. A retrospective survey of 106 cats 
with feline myocardial disease from 1994 to 
2001 from Europe revealed that DCM was 
diagnosed in approximately 10% of the cases in this series. In the author’s experience, the 
prevalence of feline idiopathic DCM may be 
less than 10%.
Species
Cat
Because the prevalence is low, breed predilections 
are not clearly defined. That said, the Burmese 
cat may have an increased incidence.
9 years (5–13 years).
None. (One study cites a male predisposition, 
while another states a female overrepresentation.)
SIGNS
• Cats with idiopathic DCM usually present 
for signs of CHF .
• They are rarely diagnosed prior to onset of 
• Signs related to low cardiac output—
anorexia, weakness, depression.
• Signs related to CHF—dyspnea, tachypnea.
• Signs related to ATE—sudden-onset pain 
and paraparesis.
• Heart rate can be fast, normal, or slow.
• Soft systolic heart murmur.
• Weak left cardiac impulse.
• Gallop sound.
• Possible arrhythmia.
• Prolonged capillary refill time.
• Quiet lung sounds (pleural effusion).
• Crackles (pulmonary edema).
• Ascites.
• Hypokinetic femoral pulses.
• Possibly, posterior paresis and pain as a 
result of ATE.
CAUSES
The underlying etiology of idiopathic DCM 
remains unknown, although a genetic 
predisposition has been identified in some 
families of cats. Taurine deficiency was a 
common cause of secondary myocardial 
failure before 1987.
  DIAGNOSIS
• Taurine deficiency DCM; because primary 
idiopathic DCM and taurine deficiency have 
similar clinical presentations, cats with 
myocardial failure should be assumed to have taurine deficiency until shown to be 
unresponsive to taurine.
• Myocardial failure secondary to long -
standing congenital or acquired left 
ventricular volume overload diseases.
• End-staged remodeled hypertrophic 
cardiomyopathy may manifest with a dilated 
hypocontractile heart.
• Arrhythmogenic right ventricular 
Many cats will have prerenal azotemia related 
to low cardiac output.
• Ensure that thyroid concentrations are normal.
• Plasma taurine concentrations less than 
40 nmol/L or whole blood taurine 
concentrations less than 250 nmol/L, are 
subnormal and suggestive of taurine 
deficiency DCM. Taurine assays are 
performed at a limited number of institutions 
and require special handling.
• Cardiac biomarkers such as plasma amine 
terminal B-type natriuretic peptide (NT-proBNP) 
and cardiac troponin I (cTnI) concentrations 
would be elevated in a cat with CHF due to 
idiopathic DCM.
IMAGING
• Radiography often shows pleural effusion 
or pulmonary edema.
• Generalized cardiomegaly.
• Diagnostic modality of choice.
• Characteristic findings include thin ventricular 
walls, enlarged left ventricular end-systolic and 
end-diastolic dimensions, left atrial enlargement, 
and low fractional shortening.
• Pleural and pericardial effusion may be 
visualized.
• Spontaneous echocardiographic contrast or 
a thrombus may be visualized.
ECG
• ECG may be normal or may show left atrial 
or ventricular enlargement patterns.
• Both ventricular and supraventricular 
arrhythmias can be seen.
Pleural Effusion Analysis
• Pleural effusion typically is a modified 
transudate with total protein <4 g/dL and 
nucleated cell counts of less than 2,500/mL; 
chylous effusion may also be present.
• Analysis of the pleural effusion is important 
to rule out other causes of pleural effusion 
such as pyothorax, infectious peritonitis, or 
lymphosarcoma.
• Heart : body ratio is increased.
• All four cardiac chambers are dilated;

230  Blackwell’s Five-Minute Veterinary Consult  
Cventricular walls are thin and left ventricular 
lumen is enlarged.
• Valve anatomy is normal.
• Histopathology shows myocytolysis and 
myocardial fibrosis.
  TREATMENT
These cats usually present in CHF and should 
be treated as inpatients, typically in an 
intensive care setting until more stable.
• Thoracocentesis is often utilized for both 
therapeutic and diagnostic purposes.
• Supplemental oxygen therapy is beneficial 
for cats in CHF to decrease the work of 
breathing.
• If hypothermic, cautious external heat 
(incubator or heating water pad) is 
ACTIVITY
Indoors only after hospital discharge to 
reduce stress. Let cat dictate its own activity.
DIET
These cats typically are anorexic, thus 
tempting their appetite with many types of 
food may be necessary. Eventually, a 
low-sodium diet is recommended.
Some cats will need chronic intermittent 
thoracocentesis to manage significant 
accumulations of pleural effusion despite 
medical therapy.
• Furosemide is recommended to manage 
pulmonary edema and pleural effusion. 
Recommended dose range is 1–4 mg/kg 
q8–12h. Initially, administer parenterally 
then switch to oral. Chronically the lowest 
effective dose of furosemide is recommended.
• Pimobendan, an inodilator, is also recomm -
ended to strengthen contractility and provide 
some vasodilation. Recommended dose range is 
0.1–0.3 mg/kg PO q12h. Although 
pimobendan is not currently licensed for use in 
cats, several recent publications have demonstrated 
its safety in cats and possibly a beneficial effect, 
albeit in retrospective studies. One study in cats 
with non-taurine-responsive DCM that were 
treated with pimobendan had a median survival 
time that was four times longer than the cats 
not treated with pimobendan (49 vs. 12 days).
• Taurine supplementation is recommended 
initially in all cats with DCM at 250 mg PO q12h, until it is demonstrated that the patient 
is unresponsive to taurine or is not taurine 
deficient based on diagnostic testing.
• Nitroglycerin (2% ointment) one-fourth to 
one-half inch applied topically can be used in 
conjunction with diuretics in the acute 
management of severe CHF to further reduce 
preload. Nitroglycerin will lower the dose of 
furosemide and is particularly useful in 
patients with hypothermia or dehydration.
• Enalapril or benazepril, at a dose of 
0.25–0.5 mg/kg PO q24h, is recommended 
to reduce afterload and preload as soon as the 
cat is able to take oral medications and is 
clinically stable. Use with caution and 
possibly avoid if creatinine >2.5 mg/dL.
• Digoxin is optionally recommended to 
strengthen contractility and for its positive 
neurohumoral effects at a dose of 0.03 mg/
cat (one-fourth of a 0.125 mg tablet) or 
0.01 mg/kg PO q48h. Digoxin can be given 
concurrently with pimobendan. However, 
digoxin is often omitted when pimobendan 
is given because of the difficulties in giving a 
cat several pills and digoxin’s side-effect 
profile.
• Dobutamine at extremely low dosages can 
be given to a patient with severe signs of CHF 
and low cardiac output that cannot take oral 
medications. Dose varies 0.25–5  μg/kg/
minute IV CRI. ECG monitoring is 
• Because ATE is a concern, an antithrom -
botic agent is also recommended. Clopidogrel 
given at a dose of 18.75 mg (one-fourth of a 
75 mg tablet) PO q24h is generally the 
author’s preferred antithrombotic agent. 
Other options include aspirin 81 mg PO 
q72h (with food) or low molecular weight 
heparin (e.g., dalteparin 100–150 units/kg 
SC q8–24h or enoxaparin 1 mg/kg SC 
q12–24h).
• Antiarrhythmic drugs may also be needed 
to control supraventricular or ventricular 
arrhythmias. If hemodynamically significant 
supraventricular tachycardia or rapid atrial 
fibrillation is present, diltiazem is recomm -
ended. Usually, diltiazem is given orally in 
either a non-sustained-release formulation 
(7.5 mg/cat PO q8h) or a sustained-release 
oral formulation (Cardizem CD® at 10 mg/kg 
PO q24h or Dilacor XR® 30 mg/cat [or 1/2 
of an inner 60 mg tablet] PO q12h). 
Diltiazem is also available in an injectable 
formulation for urgent control of a 
supraventricular arrhythmia in a cat that 
cannot take oral medications (0.05–0.1 mg/kg 
slow IV, repeated PRN up to 0.25 mg/kg). 
If rapid and sustained ventricular tachycardia, 
lidocaine slow IV 0.2–0.5 mg/kg (repeat once 
or twice max) or sotalol PO 2 mg/kg q12h is 
• Beta blockers, such as atenolol, may be 
useful in the chronic management of both supraventricular and ventricular arrhythmias. 
Beta blockers are used in the long-term 
management of DCM in humans because of 
their positive myocardial effects and survival 
benefit. Clinical experience is limited in feline 
DCM and they must be used cautiously, as 
they acutely decrease contractility and could 
worsen CHF . Recommended dose ranges 
from 3.125 to 6.25 mg PO q12–24h. Start 
low and titrate up based on heart rate and 
• Unless needed for acute cardiac rhythm 
control, drugs such as calcium channel 
blockers (diltiazem) or beta-adrenergic 
blockers may reduce contractility and lower 
cardiac output. Use cautiously.
• Overzealous diuretic and vasodilation 
therapy may cause azotemia and electrolyte 
disturbances.
• Digoxin should not be used if renal 
insufficiency is documented or suspected.
• Enalapril or benazepril should be used with 
caution and possibly withheld if serum 
creatinine is >2.5 mg/dL.
• Dobutamine may cause seizures and cardiac 
  FOLLOW-UP
• Repeat examination with ideally blood 
pressure, diagnostic imaging (either a 
thoracic radiograph or focused thoracic 
ultrasound for fluid assessment), and 
chemistry panel within 1 week to determine 
response of therapy.
• Home resting respiratory rate monitoring is 
helpful to determine need for diuretic dose 
adjustment or thoracocentesis.
• Periodically monitor electrolyte and renal 
parameters. Periodically monitor for CHF 
fluid accumulation with diagnostic imaging.
• If using digoxin, serum blood concen -
trations should be measured approximately 
10–14 days after initiating therapy. Therapeutic 
range is 0.5–1.5 ng/dL 8–12 hours post-pill.
• Repeat diagnostic echocardiogram in 2–3 
months after initiating taurine supplemen -
tation to determine echocardiographic 
response to therapy. Although echocardio -
graphic response may take 2–3 months to 
assess, one should see dramatic clinical 
response within 2 weeks of initiating taurine 
therapy if cat has taurine-responsive DCM.
Ensure that cats eat a high-protein diet with 
sufficient dietary taurine. No vegetarian diets.Cardiomyopathy, Dilated—Cats  (continued)

Canine and Feline, Seventh Edition  231
C
ATE is the most feared complication of any 
feline myocardial disease.
• These cats have a poor prognosis despite 
intensive therapy. If cat is not taurine 
responsive, survival is usually weeks to 
months.
• CHF can be medically refractory and 
recurrent despite appropriate medical therapy.
• Repeated thoracocentesis may be necessary.
• CHF .
• ATE.
• Cardiac arrhythmias.SYNONYMS
Cardiomyopathy
SEE ALSO
• Aortic Thromboembolism.
• DCM = dilated cardiomyopathy.
Ferasin L, Sturgess CP , Cannon MJ, et al. 
Feline idiopathic cardiomyopathy: a 
retrospective study of 106 cats (1994–2001). 
J Feline Med Surg 2003; 5:151–159.
Hambrook LE, Bennett PF . Effect of pimobendan 
on the clinical outcome and survival of cats with 
non-taurine responsive dilated cardiomyopathy. 
J Feline Med Surg 2012; 14:233–239.Kittleson MD. Feline myocardial disease. In: 
Ettinger SJ, Feldman EC, eds. Textbook of 
Veterinary Internal Medicine, 6th ed. St. 
Louis, MO: Elsevier, 2005, pp. 1082–1103.
Lawler DF , Templeton AJ, Monti KL. Evidence of 
genetic involvement in feline dilated cardio -
myopathy. J Vet Intern Med 1993; 7:383–387.
Pion PD, Kittleson MD, Rogers QR, et al. 
Myocardial failure in cats associated with low 
plasma taurine: a reversible cardiomyopathy. 
Science 1987; 237:764–768.
Consulting Editor  Michael Aherne(continued)  Cardiomyopathy, Dilated—Cats

232  Blackwell’s Five-Minute Veterinary Consult  
CCardiomyopathy, Dilated—Dogs
  BASICS
Dilated cardiomyopathy (DCM) character­
ized by left ­ and right ­sided dilation, normal 
coronary arteries, anatomically normal 
although commonly insufficient 
atrioventricular valves, significantly decreased 
inotropic state, and myocardial dysfunction 
occurring primarily during systole; however, 
progressive diastolic dysfunction with restrictive 
physiology may also be present and is a 
negative predictor of survival.
• Myocardial failure leads to reduced cardiac 
output and congestive heart failure (CHF).
• Atrioventricular (AV) annulus dilation and 
altered papillary muscle function promote 
valvular insufficiency.
• Although left ­sided signs commonly 
predominate, evidence of severe right ­sided 
disease can occur and infrequently is the 
dominant clinical scenario.
• Renal/urologic—prerenal azotemia.
• Respiratory—pulmonary edema, 
infrequently pulmonary hypertension.
• All organ systems are affected by reductions 
in cardiac output.
GENETICS
• Genetic cause or heritable susceptibility 
strongly suspected in most breeds and 
documented in some (Portuguese water dog, 
boxer, and Doberman pinscher) with variable 
forms of inheritance.
• A genetic test is commercially available for 
causative mutations in boxer dogs (striatin) 
and Doberman pinscher (NCSU DCM 1—
pyruvate dehydrogenase kinase; NCSU DCM 
2—titin).
• These mutations are not causative in other 
predisposed breeds in which they have been 
evaluated.
• Correlations between genotype and 
phenotype have shown that Doberman 
pinschers with both mutations have, on 
average, an earlier onset of clinical disease 
with a predisposition to sudden death; boxers 
homozygous for the mutation are more likely 
to develop the DCM phenotype.
Estimated at 0.5–1.1% in predisposed breeds 
and perhaps higher in specific geographic 
regions.
None with the exception of Chagas’ cardio­
myopathy, which is limited to the southern 
United States (Gulf Coast) and both Central 
and South America.SIGNALMENT
Species
Dog
• Doberman pinscher, boxer.
• Giant breeds—Scottish deerhound, Irish 
wolfhound, Great Dane, St. Bernard, 
Newfoundland.
• Cocker spaniel, Portuguese water dog 
(juvenile).
4–10 years.
Males > females in most but not all breeds 
(minor predisposition).
SIGNS
• Respiratory—tachypnea, dyspnea, 
coughing.
• Weight loss, typically of lean muscle mass.
• Weakness, lethargy, anorexia.
• Abdominal distention.
• Syncope, usually associated with 
arrhythmias (atrial fibrillation; ventricular 
tachycardia).
• Some dogs are asymptomatic, having what 
is termed preclinical DCM, the diagnosis of 
which in specific breeds is well described.
• Breed ­specific echocardiographic parameters 
coupled with cardiac biomarkers (NT ­proBNP; 
cardiac troponin I [cTnI]) may help identify 
dogs with preclinical DCM.
• May be completely normal with preclinical 
DCM.
• Weakness, possibly cardiogenic shock.
• Hypokinetic femoral pulse from low cardiac 
output.
• Pulse deficits with atrial fibrillation, 
ventricular or supraventricular premature 
contractions, and paroxysmal ventricular 
• Jugular pulses from tricuspid regurgitation, 
arrhythmias, or right ­sided CHF .
• Breath sounds—muffled with pleural 
effusion; crackles with pulmonary edema.
• S3 or summation gallop sounds.
• Mitral and/or tricuspid regurgitation murmurs 
are common but usually focal and soft.
• Auscultatory evidence of cardiac arrhythmia 
is common.
• Slow capillary refill time, infrequent cyanosis.
• Hepatomegaly with or without ascites.
CAUSES
• Majority of cases represent familial 
abnormalities of structural, energetic, or 
contractile cardiac proteins, some of which 
have been identified.
• Nutritional deficiencies (taurine and/or 
carnitine) have been documented in several 
breeds including golden retriever, boxer, Newfoundland, and cocker spaniel; diet ­
associated DCM, which may be associated 
with taurine deficiency, commonly secondary 
to boutique, exotic ­ingredient, or grain free 
(BEG) diets, is increasing recognized and 
potentially reversible.
• Viral, protozoal, and immune ­mediated 
mechanisms have been proposed but not proven.
• Doxorubicin toxicity.
• Hypothyroidism and persistent tachy­
arrhythmias (sometimes associated with 
congenital tricuspid valve malformation) may 
cause reversible myocardial failure.
  DIAGNOSIS
• Myxomatous valvular degeneration.
• Congenital heart disease.
• Heartworm disease.
• Bacterial endocarditis.
• Cardiac tumors and pericardial effusion.
• Airway obstruction—foreign body, 
neoplasm, laryngeal paralysis.
• Primary pulmonary disease—bronchial 
disease, pneumonia, neoplasia, aspiration, 
vascular disease (e.g., heartworms).
• Noncardiogenic pleural effusions 
(e.g., pyothorax, hemothorax, chylothorax).
• T rauma resulting in diaphragmatic hernia, 
pulmonary hemorrhage, hemothorax, 
pneumothorax.
Routine hematologic tests and urinalysis are 
usually normal unless altered by severe 
reductions in cardiac output or severe 
elevations in venous pressures (e.g., prerenal 
azotemia, high alanine aminotransferase, 
hyponatremia), therapy for heart failure 
(e.g., hyponatremia, hypokalemia, hypo­
chloremia, azotemia, and metabolic alkalosis 
from diuresis), or concurrent disease.
Cardiac biomarkers including NT ­proBNP 
and cTnI are elevated in both the preclinical 
and clinical stages of the disease. Clinical 
studies investigating use of these markers for 
diagnosis, prognosis, and optimization of 
therapy are ongoing.
IMAGING
• Typically normal in the preclinical phase.
• Generalized cardiomegaly and signs of 
CHF are common.
• Left ventricular (LV) enlargement and left 
atrial enlargement may be most evident in 
early cases.
• In some cases, the degree of cardiomegaly 
may be less than expected for the severity of 
clinical signs; it is also often substantially less 
than would be expected in a dog with

Canine and Feline, Seventh Edition  233
C
primary valvular heart disease and comparable 
• Pleural effusion, hepatomegaly, ascites.
• Gold standard for diagnosis.
• LV dilation often precedes overt reductions 
in indices of systolic function.
• Ventricular and atrial dilation.
• Indices of myocardial systolic function 
(fractional shortening [FS%]), ejection 
fraction, area shortening, and mitral annular 
motion by tissue Doppler imaging may be 
reduced.
• Spectral Doppler studies may confirm 
decreased velocity and/or acceleration of 
trans­aortic flow as well as mitral regurgitation 
and/or tricuspid regurgitation.
• Doppler evidence of restrictive LV filling is 
associated with decreased survival.
DIAGNOSTIC TESTS
ECG
• Sinus rhythm or sinus tachycardia with isolated 
atrial or ventricular premature complexes.
• Atrial fibrillation and ventricular tachycardia 
(paroxysmal or sustained) are very common 
in Doberman pinschers.
• Boxers commonly have isolated ventricular 
arrhythmias without evidence of functional or 
anatomic heart disease.
• Prolonged QRS (>0.06 second), possible 
increased voltages (R >3 mV lead II), 
suggesting LV enlargement.
• May have “sloppy” R wave descent with 
ST­T coving, suggesting myocardial disease or 
LV ischemia.
• May have low voltages (pleural or pericardial 
effusion, concurrent hypothyroidism).
• Dilation of all chambers with or without 
thinning of chamber walls.
• Slightly thickened endocardium with pale 
areas within myocardium (necrosis, fibrosis).
• T wo histologically distinct forms—fatty 
infiltration: degenerative type seen in boxers 
and Doberman pinschers; and attenuated 
wavy fiber type: seen in many giant ­, large ­, 
and medium ­sized breeds, including some 
boxers and Doberman pinschers.
  TREATMENT
With the exception of severely affected dogs 
(life­threatening arrhythmias, severe 
pulmonary edema, cardiogenic shock), most 
therapy can be administered on an outpatient 
basis.
ACTIVITY
Allow the dog to choose its own level of 
activity.DIET
• During initial therapy for clinical signs, 
simply maintaining adequate caloric intake is 
paramount.
• Goal—reduce dietary sodium intake to 
<12–15 mg/kg/day.
• Severe sodium restriction is typically not 
necessary when using potent cardioactive 
therapy and may adversely affect appetite.
• Best to use commercially prepared diets.
• Emphasize potential signs associated with 
progression of disease and adverse side effects 
of medication.
• Monitoring sleeping respiratory rate often 
gives insight into impending decompensation.
First identify patient problems—CHF (left or 
right­sided), arrhythmia, hypothermia, renal 
failure, shock.
Preclinical Disease
• There is clinical evidence (PROTECT T rial) 
that early intervention with pimobendan 
monotherapy substantially changes the course 
of preclinical disease in Doberman pinschers.
• These results are routinely extrapolated to 
other breeds, but have not been proven.
• Critical evaluation suggests that early 
intervention with monotherapy using an 
angiotensin ­converting enzyme (ACE) 
inhibitor is of minimal or no survival benefit 
in preclinical disease.
Initial Stabilization
• T reat hypoxemia with oxygen adminis­
tration; prevent heat loss if hypothermic 
(warm environment).
• If pulmonary edema—furosemide 
(1–4 mg/kg IM/IV, then 1–2 mg/kg q6–12h 
for first 1–3 days), or CRI 1–2 mg/kg/h 
(author’s preference).
• 2% topical nitroglycerin for first 24–48h 
for severe pulmonary edema—apply 1 inch–2 
inches q8h (beware of hypotension in both 
patients and staff).
• If significant pleural effusion—drain each 
hemithorax.
• If severe heart failure and cardiogenic 
shock—dobutamine may be indicated; this 
drug may exacerbate arrhythmias, particularly 
in hypoxic dogs; oral pimobendan (see dosing 
below) may have important acute (2–4h) 
hemodynamic benefit as well; IV pimobendan 
(0.15 mg/kg) is available in select countries.
• Dobutamine 5–15  μg/kg/min infused for 
24–72h with care (start low and gradually 
up­titrate based on response).• If paroxysmal ventricular tachycardia is 
present—administer lidocaine slowly in 
2 mg/kg boluses (up to 8 mg/kg total over 
30 min) to convert to sinus rhythm; follow 
with lidocaine infusion (50–100  μg/kg/min).
• If lidocaine is ineffective—administer 
procainamide slowly at dose of 2–5 mg/kg 
(up to 15 mg/kg) IV to convert to sinus 
rhythm; follow with 25–50  μg/kg/min CRI 
(beware of proarrhythmia and infrequently 
hypotension).
Maintenance Therapy
• ACE inhibitors (enalapril, benazepril, 
lisinopril) are considered cornerstone of 
therapy for DCM.
• Enalapril (0.25–0.5 mg/kg PO q12h), 
benazepril (0.5 mg/kg PO q12–24h), or 
lisinopril (0.5 mg/kg PO q 12–24h) should 
be initiated early in the therapeutic regimen.
• Furosemide (1–4 mg/kg PO q8–12h) is 
used to control signs of congestion.
• Torsemide (0.1–0.4 mg/kg PO q8–12h) is 
commonly employed as an alternative to 
furosemide, particularly in later ­stage disease.
• Spironolactone (1–2 mg/kg PO q12h) may 
impart an independent survival benefit by 
blocking aldosterone; higher doses can be 
used for refractory heart failure (2–4 mg/kg 
PO q12h).
• Hydrochlorthiazide (1–2 mg/kg PO q12h) 
may be beneficial as a third diuretic.
• Beta blockers can be used cautiously once 
heart failure is controlled with other drugs 
(see Precautions); if tolerated, they may 
improve myocardial function with chronic 
use; carvedilol (0.25–1.25 mg/kg PO q12h) is 
an alpha and beta blocker with antioxidant 
activity: start at the low end of the dose range 
and gradually up ­titrate over a 6 ­week period 
if tolerated; consult with a cardiologist before 
using beta blockers in clinical DCM patients 
as can result in rapid and profound clinical 
deterioration.
• Pimobendan (0.25–0.3 mg/kg PO q12h) is 
a calcium ­sensitizing drug and a vasodilating, 
positive inotrope (inodilator) that, when 
added to furosemide, ACE inhibitors, and 
spironolactone improves functional heart 
failure class and in Doberman pinschers 
increases survival time; the author has 
administered pimobendan 0.5 mg/kg PO q8h 
in refractory cases with perceived clinical 
benefit.
• The role of carnitine and taurine in therapy 
of DCM remains controversial; however, 
American cocker spaniels with DCM 
generally respond favorably to taurine and 
l­carnitine supplementation, but still require 
additional cardiac medications.
Arrhythmias
• In atrial fibrillation, slowing of ventricular 
rate response typically achieved with chronic 
administration of extended ­release diltiazem (continued)  Cardiomyopathy, Dilated—Dogs

234  Blackwell’s Five-Minute Veterinary Consult  
C(Dilacor®) 2–7 mg/kg PO q12h, or atenolol 
0.75–1.5 mg/kg PO q12h (never start in 
patient with active CHF), occasionally 
combined with digitalis at dose of 0.005 mg/
kg PO q12h; therapeutic drug monitoring 
recommended when administering digoxin.
• Therapeutic goal is obtaining resting 
ventricular rate of 100–140 bpm.
• At­home monitoring with AliveCor Kardia 
device.
• This therapy merely controls ventricular rate, 
by depressing atrioventricular nodal conduction; 
generally does not convert rhythm from atrial 
fibrillation to sinus rhythm.
• Amiodarone (10–15 mg/kg PO q24h for 
7–10 days followed by 5–10 mg/kg PO 
q24h) may either control ventricular response 
rate or in some cases result in conversion to 
normal sinus rhythm.
• Chronic oral therapy for ventricular 
tachycardia includes sotalol (1–2 mg/kg PO 
q12h), mexiletine (5–10 mg/kg PO q8h), or 
amiodarone (5–10 mg/kg PO q24h).
• Mexiletine can be combined with sotalol if 
necessary.
Digoxin should be avoided in severe uncontrolled 
paroxysmal ventricular tachycardia, in animals 
with compromised renal function, and in 
animals with important hypokalemia.
• Calcium channel blockers and notably beta 
blockers are negative inotropes and may have 
acute adverse effect on myocardial function; 
numerous human studies, however, have 
suggested that chronic administration of beta 
blockers may be of benefit in DCM.
• Combination of diuretics and ACE 
inhibitors may result in azotemia, especially 
in patients with severe heart failure or 
preexisting renal dysfunction, and must be 
closely monitored.POSSIBLE INTERACTIONS
• Quinidine, amiodarone, and diltiazem may 
increase serum digoxin levels and predispose 
to digitalis intoxication.
• Renal dysfunction, hypothyroidism, and 
hypokalemia predispose to digitalis intoxication.
• Other vasodilators, including hydralazine 
and amlodipine, may be used instead of or in 
addition to ACE inhibitors (beware of hypo ­ 
tension).
• Role of co ­enzyme Q10, fish oil, and 
arginine remains to be determined.
  FOLLOW-UP
• Serial clinical examinations, thoracic 
radiographs, blood pressure measurements, 
routine serum biochemical evaluations 
(including electrolytes), and electrocardio­
graphy are most helpful.
• Repeat echocardiography is rarely informative 
or indicated.
• Serial evaluation of serum digoxin levels 
(therapeutic range: 0.5–1 ng/mL) taken 6–8 
hours post ­pill and serum biochemistries may 
help prevent iatrogenic problems.
• Sudden death due most commonly to 
arrhythmias.
• Iatrogenic problems associated with medical 
management (see above).
• Always fatal unless associated with 
nutritional deficiencies.
• Death usually occurs 6–24 months 
following diagnosis.
• Dobermans typically have worst prognosis; 
however, with addition of pimobendan, survival following identification in preclinical  
phase averages over 700 days.
• Atrial fibrillation, paroxysmal ventricular 
tachycardia, Doppler evidence of restrictive 
LV filling, markedly decreased FS%, homo  ­
zygosity for known mutations (boxer), or 
presence of multiple mutations (Doberman 
pinschers) are believed to be markers for 
shortened survival and increased risk for 
sudden arrhythmogenic death.
Prevalence increases with age.
SYNONYMS
• Congestive cardiomyopathy.
• Giant ­breed cardiomyopathy.
SEE ALSO
• Atrial Fibrillation and Atrial Flutter.
• ACE = angiotensin ­converting enzyme.
• BEG = boutique, exotic ­ingredient, or grain 
free.
• FS% = percent fractional shortening.
https://cardiaceducationgroup.org
Author  Matthew W. Miller
available onlineCardiomyopathy, Dilated—Dogs  (continued)

Canine and Feline, Seventh Edition  235
C
  BASICS
Inappropriate concentric hypertrophy of the 
ventricular free wall and/or the interventricular 
septum of the nondilated left ventricle. The 
disease occurs independently of other cardiac 
or systemic disorders.
• Diastolic dysfunction results from a 
thickened, less compliant left ventricle.
• High left ventricular filling pressure 
develops, causing left atrial (LA) enlarge  - 
ment.
• Pulmonary venous hypertension causes 
pulmonary edema. Some cats develop 
biventricular failure (i.e., pulmonary edema, 
pleural effusion, small volume pericardial 
effusion without tamponade, and infrequently 
ascites).
• Stasis of blood in the large left atrium 
predisposes the patient to aortic thrombo -
embolism (ATE).
• Dynamic aortic outflow obstruction and 
systolic anterior mitral motion (SAM) with 
secondary mitral insufficiency may occur, but 
unlike in humans, appears not to affect prognosis.
• Recent evidence suggests that some cats 
with apparent hypertrophic cardiomyopathy 
(HCM) and congestive heart failure (CHF) 
actually have transient myocardial thickening, 
often associated with high serum troponin I 
concentrations. These cats are younger than 
average for HCM, with on average less severe 
left ventricular (LV) hypertrophy, and they 
can experience resolution of both CHF and 
LV hypertrophy.
• Cardiovascular—CHF , ATE, and 
• Pulmonary—dyspnea if CHF develops.
GENETICS
Some families of cats have been identified 
with a high prevalence of the disease, and 
the disease appears to be an autosomal 
dominant trait in Maine coon cats and 
ragdoll cats, due to a mutation in the 
myosin-binding protein C (MyBPC) gene. 
The genetics have not been definitively 
determined in other breeds; however, the 
Maine coon and ragdoll mutations have not 
been identified in affected Sphynx, Norwegian 
forest cats, Bengals, Siberians, or British 
Unknown, but relatively common. May be as 
high as 15% of the population.
Species
CatBreed Predilections
Maine coon cats, ragdolls, Sphynx, British 
and American shorthairs, and Persians.
• 5–7 years, with reported ages of 3 months– 
17 years. Some breeds of cats including 
ragdolls and Sphynx may develop the disease 
at a younger age (average of 2 years).
• HCM is most often a disease of young to 
middle-aged cats; unexplained murmurs in 
geriatric cats are more likely associated with 
hyperthyroidism or hypertension.
Male
SIGNS
• Dyspnea, tachypnea.
• Sudden death.
• Coughing is uncommon in cats with HCM 
and suggests primary pulmonary disease.
• Gallop rhythm (S3 or S4).
• Systolic murmur in approximately half of 
affected cats.
• Apex heartbeat may be exaggerated.
• Muffled heart sounds, lack of chest 
compliance, and dyspnea characterized by 
rapid shallow respirations may be associated 
with pleural effusion.
• Dyspnea and crackles if pulmonary edema 
is present.
• Weak femoral pulse.
• Acute pelvic limb paralysis with cyanotic 
pads and nailbeds, cold limbs, and absence of 
femoral pulse in animals with ATE; emboli 
rarely affect thoracic limbs.
• Arrhythmia in some animals.
• May have no clinical signs.
CAUSES
• Usually unknown—multiple causes exist.
• MyBPC mutations in some cats with HCM.
Possible Causes
• Abnormalities of contractile protein myosin 
or other sarcomeric proteins (e.g., troponin, 
myosin-binding proteins, tropomyosin).
• Abnormality affecting catecholamine-
influenced excitation contraction coupling.
• Abnormal myocardial calcium metabolism.
• Collagen or other intercellular matrix 
abnormality.
• Growth hormone excess.
• Dynamic LV outflow obstruction may 
contribute to secondary LV hypertrophy.
Offspring of animals with familial mutations 
of MyBPC.  DIAGNOSIS
• Other forms of cardiomyopathy.
• Aortic stenosis.
• Acromegaly.
• Noncardiac causes of pleural effusion.
• Results usually normal.
• Prerenal azotemia in some animals.
• MyBPC assay; mutation differs for Maine 
coon cats and ragdoll cats.
• In cats >6 years old, check thyroid hormone 
concentration; hyperthyroidism causes 
myocardial hypertrophy that might be 
confused with HCM.
• Serum NT-proBNP concentrations higher in 
cats with HCM than in normal cats, and 
higher still in cats with symptomatic HCM. 
SNAP NT-proBNP point-of-care testing is also 
available to help differentiate symptomatic 
cats with HCM from those that are sympto  - 
matic from other causes. Send-out serum 
NT-proBNP testing is useful in identifying cats 
with suspicion of HCM from asymptomatic cats 
with abnormal physical exam findings (e.g., 
murmur). Follow-up echocardiography 
indicated in cats with serum NT-proBNP 
concentrations in “equivocal” or “high” range, 
or positive SNAP results.
IMAGING
• Dorsoventral radiographs often reveal a 
valentine-appearing heart because of atrial 
enlargement and a left ventricle that comes to 
a point.
• Pulmonary edema, pleural effusion, or both 
in some animals.
• Radiographs may be normal in asymptomatic 
cats.
• Different forms of cardiomyopathy cannot 
be reliably differentiated by radiography.
• Hypertrophy of interventricular septum 
(IVS) or LV posterior wall (diastolic wall 
thickness >6 mm).
• Hypertrophy may be symmetric (affecting 
IVS and posterior wall) or asymmetric (affecting 
IVS or posterior wall, but not both).
• Hypertrophy of papillary muscles.
• Normal or high fractional shortening.
• Normal or reduced LV lumen.
• LA enlargement.
• Systolic anterior motion of mitral valve 
(some animals).
• LV outflow obstruction (some animals); 
specialized Doppler studies performed by Cardiomyopathy, Hypertrophic—Cats

236  Blackwell’s Five-Minute Veterinary Consult  
Cexperienced sonographers often reveal LV 
relaxation abnormalities (e.g., mitral inflow 
E : A wave reversal).
• Thrombus in left atrium (rare).
• Note:  there is some overlap between normal 
cats (especially ketaminized or dehydrated) 
and cats with mild HCM. Correlate echo 
findings with physical findings. Presence of 
LA enlargement favors HCM.
ECG
• Sinus tachycardia (heart rate >240) common 
with heart failure; however, some cats with severe 
heart failure and hypothermia are bradycardic.
• Atrial and ventricular premature complexes 
seen more often in cats with cardiomyopathy, 
but also occasionally seen in normal cats.
• Atrial fibrillation seen in some advanced cases.
• Left axis deviation often seen.
• Prolongation of QT interval and QTc (QT 
interval corrected for heart rate) often seen 
with LV hypertrophy.
• Cannot differentiate different forms of 
cardiomyopathy; may be normal.
Systemic Blood Pressure
• Normotensive or hypotensive.
• Evaluate blood pressure in all patients with 
myocardial hypertrophy to rule out systemic 
hypertension as cause of hypertrophy.
• Nondilated left ventricle with hypertrophy 
of IVS or LV free wall.
• Mitral valve thickening.
• Myocardial hypertrophy with disorganized 
alignment of myocytes (myofiber disarray).
• Interstitial fibrosis.
• Myocardial scarring.
• Hypertrophy and luminal narrowing of 
intramural coronary arteries.
  TREATMENT
Cats with CHF should be hospitalized.
• Minimize stress.
• Oxygen if dyspneic.
• Warm environment if hypothermic.
ACTIVITY
Restricted with CHF .
DIET
Modest to moderate sodium restriction in 
animals with CHF .
• Many cats diagnosed while asymptomatic 
eventually develop CHF and may develop 
ATE and die suddenly.
• If cat is receiving warfarin, dalteparin, 
enoxaparin (Lovenox®), or combination of clopidogrel and any of those medications, 
minimize potential for trauma and 
subsequent hemorrhage.
Furosemide
• Dosage—1–2 mg/kg PO/IM/IV q8–24h.
• Critically dyspneic animals often require 
high dosage (4 mg/kg IV); this dose can be 
repeated in 1 hour if cat still severely 
dyspneic; indicated to treat pulmonary 
edema, pleural effusion, and ascites.
• Cats are sensitive to furosemide and prone 
to dehydration, prerenal azotemia, and 
hypokalemia.
• Once pulmonary edema resolves, taper to 
lowest effective dose.
Pimobendan
• Dosage—0.25–0.3 mg/kg PO q12h.
• Appears to be useful in management of 
CHF (e.g., pulmonary edema or pleural 
effusion) in cats with HCM, possibly by 
enhancing diastolic function and LA fractional 
shortening; not used in management of 
asymptomatic HCM at this time.
• Not currently licensed for use in cats.
Angiotensin-Converting Enzyme (ACE) 
• Dosage—enalapril or benazepril 0.25–
0.5 mg/kg PO q24h.
• Indications in cats with HCM not well 
defined—authors currently use for CHF .
Beta Blockers
• Dosage—atenolol (6.25–12.5 mg/cat PO 
q12h).
• Beneficial effects may include slowing of 
sinus rate, correcting atrial and ventricular 
arrhythmias, platelet inhibition.
• More effective than diltiazem in controlling 
dynamic outflow tract obstruction.
• Role in asymptomatic patients 
unresolved, but many clinicians use if 
dynamic outflow obstruction and hyper -
trophy present.
• Contraindicated in presence of CHF .
Diltiazem
• Dosage—7.5–15 mg/cat PO q8h or 10 mg/kg 
PO q24h (Cardizem® CD) or 30 mg/cat q12h 
(Dilacor XR®).
• Beneficial effects may include slower sinus 
rate, resolution of supraventricular arrhythmias, 
improved diastolic relaxation, coronary and 
peripheral vasodilation, platelet inhibition.
• May reduce hypertrophy and LA 
dimensions in some cats.
• Role in asymptomatic patients unresolved.
Aspirin
• Dosage—81 mg/cat q2–3 days if severe 
atrial enlargement.• Depresses platelet aggregation, hopefully 
minimizing risk of thromboembolism.
• Warn owners that thrombi can still 
develop despite aspirin administration; 
aspirin appears to be not as effective as 
clopidogrel (1/4 of 75 mg tablet PO q24h) 
in prevention of ATE, at least in cats with 
previous embolic episode.
Nitroglycerin Ointment
• Dosage—one-fourth inch/cat topically 
applied q6–8h or 2.5 mg/24h patch.
• Often used in acute stabilization of cats with 
severe pulmonary edema or pleural effusion.
• When used intermittently, may be useful 
for long-term management of refractory cases.
Avoid beta blockers in cats with emboli; these 
agents cause peripheral vasoconstriction. If 
beta blockers must be used in this setting for 
arrhythmia control, choose beta-1 selective 
blocker such as atenolol.
Use ACE inhibitors cautiously in azotemic 
animals.
Torsemide
• Dosage—0.1–0.5 mg/kg q24h, sometimes 
with dose escalation to q12h.
• Used as substitute for furosemide in 
refractory pulmonary edema or pleural 
effusion in cats with apparently normal (or at 
least stable) renal function.
• Monitor renal function closely in first days 
after switching to torsemide.
Spironolactone
• Dosage—1 mg/kg q12–24h.
• Used in conjunction with furosemide in 
cats with CHF , especially refractory effusions.
• May cause facial pruritis.
Warfarin and Low Molecular Weight 
Heparin
• Used sometimes in cats at high risk for 
• See Aortic Thromboembolism.
Clopidogrel
• Dosage—18.75 mg/cat/day.
• Platelet function inhibitor, superior to 
aspirin in cats with previous ATE.
Beta Blocker plus Diltiazem
• Cats that remain tachycardic on a single 
agent can be treated cautiously with a 
combination of a beta blocker and diltiazem.
• Monitor for bradycardia and hypotension.
  FOLLOW-UP
• Observe closely for dyspnea, lethargy, 
weakness, anorexia, and painful posterior 
paralysis or paresis.Cardiomyopathy, Hypertrophic—Cats  (continued)

Canine and Feline, Seventh Edition  237
C
• If treating with warfarin, monitor prothrom  - 
bin time.
• If treating with ACE inhibitor or spirono -
lactone, monitor renal function and 
electrolytes.
• Repeat echocardiogram in 6 months to 
assess efficacy of treatment for hypertrophy. If 
beta blocker or diltiazem was prescribed in 
asymptomatic animal and there is evidence of 
progressive hypertrophy/LA enlargement, 
consider switching to another class of 
medications (or adding an ACE inhibitor) 
and recheck 4–6 months later.
• Echocardiographic evaluations that reveal 
LA diameters >2 cm or loss of LV systolic 
function should prompt more aggressive 
prophylaxis against ATE (e.g., clopidogrel 
with low molecular weight heparin).
Avoid stressful situations that might 
precipitate CHF .
• Heart failure.
• ATE and paralysis.
• Cardiac arrhythmias/sudden death.
• Animals homozygous for MyBPC mutations 
more likely to develop severe HCM and at 
earlier age than heterozygous animals.
• Prognosis varies considerably, probably 
because there are multiple causes. In one 
study of cats with HCM living at least 
24 hours following presentation: ∘Asymptomatic cats—median survival 
563 days (range: 2–3,778 days).
 ∘Cats with syncope—median survival 
654 days (range: 28–1,505 days).
 ∘Cats with CHF—median survival 
563 days (range: 2–4,418 days).
 ∘Cats with ATE—median survival 
184 days (range: 2–2,278 days).
 ∘Older age and larger left atria predicted 
shorter survival.
Aortic thromboembolism.
• High risk of complications.
• Avoid aspirin.
SEE ALSO
• Hypersomatotropism/Acromegaly in Cats.
• Murmurs, Heart.
• IVS = interventricular septum.• LA = left atrial.
• MyBPC = myosin-binding protein C.
• QTc = QT interval corrected for heart rate.
• SAM = systolic anterior mitral motion.
Fox PR, Keene BW, Lamb K, et al. 
International collaborative study to assess 
cardiovascular risk and evaluate long-term 
health in cats with preclinical hypertrophic 
cardiomyopathy and apparently healthy 
cats: the REVEAL study. J Vet Intern Med 
2018, 32(3):930–943.
McDonald K. Feline cardiomyopathy. In: 
Smith FWK, Tilley LP , Oyama MA, Sleeper 
MM, eds. Manual of Canine and Feline 
Cardiology, 5th ed. St. Louis, MO: 
Saunders Elsevier, 2016, pp. 153–180.
Novo Matos J, Pereira N, Glaus T, et al. 
T ransient myocardial thickening in cats 
associated with heart failure. J Vet Intern 
Med 2018, 32(1):48–56.
Romito G, Guglielmini C, Mazzarella MO, 
et al. Diagnostic and prognostic utility of 
surface electrocardiography in cats with left 
ventricular hypertrophy. J Vet Cardiol 2018, 
20(5):364–375.
Authors  Francis W.K. Smith, Jr., Bruce W. 
Keene, and Kathryn M. Meurs
available online(continued)  Cardiomyopathy, Hypertrophic—Cats

238  Blackwell’s Five-Minute Veterinary Consult  
CCardiomyopathy, Hypertrophic—Dogs
  BASICS
OVERVIEW
Hypertrophic cardiomyopathy (HCM) is 
defined as inappropriate myocardial hypertrophy 
of a nondilated left ventricle, occurring in the 
absence of an identifiable stimulus. HCM is rare 
in dogs, and is characterized by left ventricular 
(LV) concentric hypertrophy (increased wall 
thickness). The primary disease process is 
confined to the heart and only affects other 
organ systems when congestive heart failure 
(CHF) is present. Increased LV wall thickness 
leads to impaired ventricular filling (due to lack 
of compliance and abnormal relaxation), with 
resultant increases in LV end-diastolic pressure 
and left atrial (LA) pressure. LA enlargement is 
usually in response to increased LV end-diastolic 
pressure. Mitral insufficiency and/or dynamic LV 
outflow tract obstruction commonly occur 
secondary to structural and/or functional 
changes of the mitral valve apparatus caused by 
papillary muscle malalignment due to hyper  - 
trophy.
• The incidence of HCM in dogs is very low, 
thus accurate accounts of signalment are lacking.
• Young (<3 years) male dogs.
• Rottweiler, Dalmatian, German shepherd, 
pointer breeds and Boston terriers have been 
reported.
SIGNS
• Most are asymptomatic.
• Signs of left CHF predominate in sympto  - 
matic dogs.
• Syncope, generally during activity or exercise.
• Sudden death is the most commonly 
reported clinical sign.
• ± Systolic heart murmur.
• ± Gallop heart sound.
• ± Signs of left CHF (e.g., dyspnea, cyanosis, 
exercise intolerance, cough).
The cause of canine HCM is unknown. 
Genetic abnormalities in genes coding for 
myocardial contractile proteins have been 
documented in humans and cats.
  DIAGNOSIS
• Infiltrative cardiac disorders.• Thyrotoxicosis.
• Mitral dysplasia.
IMAGING
• May be normal or may show LA or LV 
• Pulmonary edema present with left CHF .
• Severe cases usually have marked LV and 
papillary muscle hypertrophy, and LA 
enlargement. Hypertrophy is usually global, 
but can be more regional or segmental 
(asymmetric). Milder forms may have subtle 
• Systolic anterior motion of the mitral valve, 
suggesting dynamic LV outflow tract 
obstruction (LVOTO), is common in dogs 
with HCM.
ECG
• May be normal.
• ST segment and T wave abnormalities have 
been reported.
• Atrial or ventricular ectopic arrhythmias 
may rarely occur.
Blood Pressure
Usually normal. Should be evaluated to rule 
out systemic hypertension as the cause of LV 
hypertrophy.
• Abnormal heart : body weight ratio.
• LV concentric hypertrophy.
• The interventricular septum may have an 
impact lesion, varying from a small opaque 
lesion to a thickened plaque.
• The mitral valve is often thickened and 
elongated.
• Varying degrees of LA enlargement may be 
present.
  TREATMENT
T reatment is generally only pursued if there is 
evidence of CHF , severe arrhythmias, or 
frequent syncope. Exercise restriction and 
sodium restriction are beneficial.
• In patients with left CHF , diuretics and 
angiotensin-converting enzyme (ACE) 
inhibitor therapy are advocated.
• In dogs with severe dynamic LVOTO, 
administration of beta blockers or calcium channel blockers has been advocated; 
however, benefit has not been proven.
• Beta blockers or calcium channel blockers 
may also improve myocardial oxygenation, 
reduce heart rate, improve LV diastolic 
function, and control arrhythmias, and 
therefore may be useful in dogs with left CHF; 
however, benefit has also not been proven.
• Positive inotropes may worsen dynamic 
LVOTO.
• Avoid calcium channel blockers in 
combination with beta blockers, as clinically 
significant bradyarrhythmias can develop.
• Avoid potent arteriolar dilators in cases 
with dynamic LVOTO. The use of milder 
vasodilators such as ACE inhibitors in dogs 
with CHF is generally well tolerated.
  FOLLOW-UP
• Depends on clinical severity. Serial 
radiography and/or echocardiography may 
help characterize disease progression and 
guide medication adjustments.
• Due to the rarity of canine HCM, 
prognostic information is lacking. In dogs 
with severe CHF or other complications, 
prognosis is generally guarded.
• LVOTO = left ventricular outflow tract 
Oyama MA. Canine cardiomyopathy. In: 
MM, eds., Manual of Canine and Feline 
Saunders Elsevier, 2016, pp. 141–152.
Ware WA. Myocardial diseases of the dog. In: 
Ware WA, Cardiovascular Disease in Small 
Animal Medicine. London: Manson/
Veterinary Press, 2011, pp. 280–299.
Larry P . Tilley.

Canine and Feline, Seventh Edition  239
C
Cardiomyopathy, Nutritional
  BASICS
OVERVIEW
• Nutritional imbalances, such as taurine and 
L-carnitine deficiency, can lead to the 
development of dilated cardiomyopathy 
(DCM) in some dogs and cats. Deficiencies 
of other nutrients (e.g., selenium, zinc, 
vitamin E, thiamine, copper, iron) or nutrient 
toxicities (e.g., iron, cobalt) also have the 
potential to alter myocardial function, 
resulting in clinical manifestations of heart 
disease. Additionally, relative nutritional 
deficiencies or toxicities may interact with 
other toxic, infectious, or genetic insults in 
certain individuals to produce DCM.
• Taurine is the most abundant free amino acid 
found in cardiac muscle, playing an important 
role in myocardial calcium regulation. Taurine 
deficiency was first reported as a cause of 
reversible DCM in cats in 1987, prompting an 
increase in the dietary taurine requirement for 
commercial cat foods, and since then DCM in 
cats is uncommon. Unlike cats, dogs should be 
able to endogenously synthesize taurine; 
however, several breeds (e.g., American cocker 
spaniel, Newfoundland, Irish wolfhound, 
golden retriever) have reported predispositions 
to taurine deficiency and resultant DCM. 
Additionally, some commercial dog foods such 
as grain-free, high-legume, lamb and rice 
formulations and high-fiber foods, have been 
associated with taurine deficiency. Oral 
taurine supplementation can effect disease 
reversal in deficient cats and significant 
improvement in dogs.
• L-carnitine, a quaternary amine, is an 
important part of enzyme systems that 
transport fatty acids into mitochondria for 
oxidization to make energy. It also has other 
important cellular metabolic and scavenging 
functions. Carnitine deficiency complicates 
some cases of DCM in dogs. Plasma 
L-carnitine deficiency in association with 
cardiomyopathy does not mean that the 
deficiency is the sole cause of the myopathy, 
although correcting the deficiency, if possible, 
makes medical and physiologic sense. In the 
dog, dietary carnitine intake influences 
plasma concentrations significantly, and oral 
carnitine supplementation is usually an 
effective means of raising plasma and 
subsequently muscle carnitine levels.
• A perceived increase in recognition of 
DCM in dogs eating boutique, exotic-
ingredient, or grain-free (BEG) dog foods in 
2018 prompted an FDA investigation into a 
possible relationship between BEG diets and 
canine DCM. The majority of affected dogs 
eating BEG diets do not appear to be taurine 
or L-carnitine deficient; however, golden 
retrievers appear to be more susceptible to 
taurine deficiency when eating these foods. The underlying cause has not yet (as of 
writing) been identified, and causation has 
not been proven. Nutritional management, 
involving diet change and in some cases 
taurine supplementation, has resulted in 
improvement or resolution of cardiomyopathy 
over a period of 3–12 months. Investigations 
are ongoing.
Dogs
• Golden retrievers, American cocker spaniels, 
Newfoundlands, English setters, St. Bernards, 
and Irish wolfhounds are reported to be 
predisposed to taurine-deficient DCM.
• L-carnitine deficiency has been reported in 
a family of boxers.
• Dogs eating BEG diets that are affected 
with suspected nutritional DCM have been 
of varied ages and breeds.
Cats
Taurine deficiency is rare in cats fed 
commercial, nutritionally balanced diets. 
Taurine-deficient DCM can occur in cats fed 
vegetarian or home-prepared diets.
SIGNS
• Clinical signs of taurine-deficient DCM are 
related to poor myocardial contractility, 
which can lead to congestive heart failure in 
some cases; these signs include lethargy, 
weakness, syncope, dyspnea and tachypnea.
• Cats may also present for reproductive 
failure, poor growth, or blindness due to 
central retinal degeneration.
• Clinical signs of carnitine deficiency can be 
diverse, ranging from clinical manifestations 
of DCM to skeletal muscle pain and exercise 
• See Cardiomyopathy, Dilated—Dogs.
• Vegetarian and home-prepared diets 
increase the risk of taurine-deficient DCM in 
cats if taurine is not exogenously supplemented 
adequately.
• Factors predisposing to taurine deficiency 
in dogs include breed (possible genetic causes) 
and dietary components; high-fiber diets, 
low-protein diets, lamb and rice diets, and 
beet pulp ingredients have been associated 
with taurine deficiency; dietary predisposition 
to taurine deficiency with these factors could 
be a result of inadequate taurine precursors 
(methionine and cysteine), low bioavailability 
of taurine and/or precursors, reduced entero- 
hepatic bile acid recycling due to high dietary 
fiber, excessive urinary taurine wasting, or 
gastrointestinal microbial interaction with 
taurine.
• Some dogs with DCM have been 
documented to have carnitine transport 
defects, in which muscle carnitine is low 
despite adequate plasma concentrations. In 
cases in which a mitochondrial enzyme defect 
causes the accumulation of a metabolite to toxic levels within the mitochondria (e.g., 
multiple Co-A dehydrogenase defects), free 
L-carnitine is used to “scavenge” potentially 
toxic excess metabolites, which appear 
harmlessly in the plasma and eventually the 
urine as carnitine esters; in these cases, the 
total amount of carnitine (free carnitine plus 
that esterified to other molecules) in the 
plasma or muscle may be normal or even 
high, but the ratio of free to esterified 
carnitine is decreased; this situation is known 
as carnitine insufficiency (since although the 
concentration of free carnitine may be within 
the normal range, it is insufficient to meet the 
body’s pathologically increased need for free 
carnitine).
• Certain families of boxers appear to be at 
especially high risk of developing symptomatic 
DCM in association with, and probably 
caused by, carnitine deficiency; a known 
first-degree relative with cardiomyopathy 
should increase the index of suspicion.
• The cause of the apparent, although unproven, 
link between BEG diets and canine DCM is 
unknown; however, the commonality of 
ingredients in these diets has drawn the 
attention of veterinary nutritionists; the high 
legume content of these foods (e.g., lentils 
and peas), less studied protein sources (e.g., 
kangaroo, alligator, bison), and other unusual 
ingredients (e.g., flaxseed) raise the possibility 
of a nutrient deficiency, toxicity, or nutrient–
nutrient interaction that may predispose to 
the development of DCM in some dogs.
  DIAGNOSIS
Normal
• Ideally, both whole blood and plasma 
taurine concentrations should be evaluated to 
assess for taurine deficiency in any dog with 
DCM; if only one blood sample can be 
analyzed, whole blood is considered a better 
indicator of long-term taurine status. Blood for 
taurine concentrations should be drawn into 
lithium heparin tubes and frozen immediately. 
The normal whole blood taurine concentration 
range for dogs (200–350 nmol/mL) has been 
questioned recently, especially in golden 
retrievers, where normal has been proposed to 
be 213–377 nmol/mL. Historically, taurine-
deficient DCM is diagnosed when whole 
blood concentrations are <150 nmol/mL in 
dogs and <200 nmol/mL in cats, or when

  DIAGNOSIS
Normal
dogs and <200 nmol/mL in cats, or when 
plasma taurine concentrations are <40 nmol/mL 
in both species; values ≤213 nmol/mL 
(whole blood) and ≤63 nmol/mL (plasma) 
have been proposed for DCM diagnosis in 
golden retrievers.
• Plasma carnitine concentrations appear to 
be a specific but insensitive indicator of

240  Blackwell’s Five-Minute Veterinary Consult  
Cmyocardial or skeletal muscle carnitine 
deficiency. Plasma free carnitine concen -
trations of less than 8 μmol/L are considered 
diagnostic of systemic carnitine deficiency; 
plasma concentrations in the normal or 
supernormal range do not rule out myocardial 
carnitine deficiency or insufficiency.
• There is no confirmatory laboratory test 
currently available to diagnose nutritional 
DCM associated with BEG diets; dogs should 
be assessed for taurine and carnitine deficiency, 
and the diagnosis is solidified by response to 
nutritional management.
IMAGING
Echocardiography is used to diagnose DCM.
• Endomyocardial biopsy is the gold standard to 
assess myocardial carnitine levels, since plasma 
carnitine concentrations are an insensitive 
indicator of muscle carnitine deficiency.
• Myocardial free carnitine concentrations 
<3.5 nmol/mg of noncollagenous protein are 
considered diagnostic of myocardial carnitine 
• Ratio of esterified to free carnitine >0.4 is 
considered diagnostic of carnitine 
insufficiency.
  TREATMENT
• Response to nutritional manipulation and 
supplementation can take months, so patients 
will require medications to support myocardial 
function (e.g., pimobendan), antagonize 
neurohormonal activation (e.g., angiotensin-
converting enzyme inhibitors and 
spironolactone), and diuretic therapy if 
congestive heart failure is present (e.g., 
furosemide).
• Taurine supplementation if taurine 
deficiency is diagnosed; if blood 
concentrations are not measured, it is reasonable to trial with supplementation and 
assess response to treatment; taurine deficiency 
associated with DCM in American cocker 
spaniels is reported to respond to both taurine 
and L-carnitine supplementation.
• T reatment with L-carnitine is indicated in 
addition to conventional treatment for DCM; 
however, some dogs, including some families 
of carnitine-deficient boxers, fail to respond 
clinically to supplementation. While supple  - 
mentation dramatically improves a small 
percentage of dogs with DCM, the overall 
efficacy of L-carnitine supplementation for 
treatment of DCM is untested. If a trial of 
metabolic supplementation is desired in the 
absence of known L-carnitine deficiency, the 
combination of L-carnitine with taurine and 
CoQ10 (100 mg as ubiquinol q8–12h) seems 
prudent.
• T ransition to a high-quality, scientifically 
backed, grain-based food with a well-studied 
protein source is critical to the recovery of 
nutritional DCM associated with BEG diets. 
The role of taurine supplementation in the 
absence of deficiency is uncertain; however, 
there is no known detriment to empiric 
supplementation, and taurine may have 
therapeutic benefits apart from correction of 
Taurine
• Dogs—250 mg PO q12h if <10 kg; 
500 mg PO q12h if 10–25 kg; 1000 mg PO 
q12h if >25 kg.
• Cats—250 mg PO q12h.
L-Carnitine
• Large-breed dogs—2 g (approximately 1 tsp 
L-carnitine powder) q8–12h.• American cocker spaniels—(in combination 
with taurine) 1 g (approximately 0.5 tsp 
L-carnitine powder) q8–12h.
  FOLLOW-UP
Repeat echocardiogram 3–6 months after 
nutritional manipulation, including amino 
acid supplementation and/or diet change. 
Improvement in myocardial function may 
take up to a year for dogs with nutritional 
N/A
N/A
None
Taurine deficiency may cause reproductive 
failure in cats.
SEE ALSO
• Cardiomyopathy, Dilated—Dogs.
• BEG = boutique, exotic-ingredient, 
grain-free.
Adin D, DeFrancesco T, Keene B, et al. 
Echocardiographic phenotype of DCM 
differs based on diet type. J Vet Cardiol 
2019, 21:1–9.
Authors  Darcy B. Adin and Bruce W. Keene
Consulting Editor  Michael AherneCardiomyopathy, Nutritional  (continued)

Canine and Feline, Seventh Edition  241
CCardiomyopathy, Restrictive—Cats
  BASICS
A rare, primary heart muscle disease character  - 
ized functionally  by severe diastolic dysfunc-
tion with restrictive left ventricular (LV) 
filling and normal to near normal systolic 
function, morphologically  by a nondilated, 
nonhypertrophied left ventricle with 
increased endocardial and/or myocardial 
fibrosis and severe atrial enlargement, and 
clinically  by congestive heart failure (CHF), 
thromboembolic disease, and cardiac death.
• Increased cardiomyofilament Ca2+ sensitivity 
leading to severely impaired myocardial 
relaxation, high myocardial stiffness due to 
endomyocardial fibrosis (endomyocardial type) 
and/or interstitial fibrosis (myocardial type), and 
disorganized myofiber architecture (disarray) are 
main characteristics of primary restricted 
cardiomyopathy (RCM); RCM-like myocardial 
changes and clinical syndromes can result from 
myocardial remodeling and dysfunction 
secondary to other causes (e.g., endomyocardi -
tis, immune-mediated disease, or end-stage 
hypertrophic cardiomyopathy). • Diastolic 
heart failure and cardiogenic arterial thrombo -
embolism (ATE) lead to high mortality.
• Cardiovascular. • Respiratory.
GENETICS
Primary RCM can be a spontaneous or 
familial disease, but is generally considered of 
genetic cause in humans with an autosomal 
dominant pattern of inheritance; several genes 
encoding sarcomeric and nonsarcomeric 
proteins can be affected; RCM-causing 
mutations have not been identified in cats.
Primary feline RCM is rare—prevalence 
ranging from 1% to 5% of all myocardial 
diseases in cats.
• Cats. • Higher prevalence in Siamese and 
oriental cats. • Middle-aged to older cats. 
• Male predisposition.
SIGNS
• Lethargy. • Weight loss. • Paresis or 
paralysis (i.e., signs of ATE). • Labored 
breathing. • Tachypnea. • Ascites. • Jugular 
venous distension. • Cyanosis.
• If not in CHF—arrhythmias. ◦ Prominent 
gallop sounds are a hallmark. ◦ Heart murmur 
uncommon. • If in CHF—above signs plus the 
following: ◦ Tachypnea. ◦ Labored breathing. 
◦ Cyanosis. ◦ Hepatomegaly or ascites with 
jugular venous distention. ◦ Pulmonary crackles. ◦ Muffled cardiac or respiratory 
sounds if pleural effusion. ◦ Paralysis or paresis 
with loss of femoral pulses; one or more 
extremities cold and painful (ATE).
CAUSES
• Primary RCM—currently unknown; 
genetic cause documented in humans. 
• Secondary RCM—late or end stage of 
underlying disease (e.g., hypertrophic 
cardiomyopathy); link between prior 
interstitial pneumonia and feline endomyo-
carditis leading to RCM suspected in one 
study.
  DIAGNOSIS
• Advanced stages of other feline cardiomyo -
pathies: ◦ Hypertrophic, dilated, arrhythmo -
genic right ventricular, non-specific phenotype, 
and tachycardia-induced cardiomyopathy. 
◦ Myocardial infarct. ◦ CHF secondary to 
thyrotoxicosis or hypertensive heart disease.
Routine chemistry panel and urinalysis 
helpful to document concurrent or compli-
cating conditions (e.g., renal failure and 
potassium depletion).
• Plasma T4 concentration in cats ≥6 years 
old. • Plasma cardiac troponin I concentra-
tion (more specific if ischemic heart disease or 
myocarditis suspected).
IMAGING
• Cardiomegaly with severe biatrial enlarge-
ment (“valentine” heart on v/d projections). 
• Interstitial or alveolar infiltrates or pleural 
effusion with pulmonary venous distention if 
in CHF .
• Note:  definitive diagnostic criteria are poorly  
defined and remain controversial. Early 
(noncongestive) RCM has rarely been 
documented in cats. • Anatomic findings 
characterizing the RCM phenotype include: 
◦ Severe biatrial enlargement. 
◦ Nonhypertrophied, nondilated left ventricle 
(normal chamber dimension, normal wall 
thickness). ◦ Severe enlargement of the left 
atrium with spontaneous echocardiographic 
contrast or thrombi frequently seen. 
◦ Prominent, often diffuse echogenic scar 
(“moderator bands,” false tendons) leading to a 
small LV lumen and narrowing at the mid-
ventricle (endomyocardial fibrosis or “bridging” 
fibrosis). ◦ Focal areas of highly echogenic and 
often thin myocardium indicative of ischemia or 
scarring. ◦ Myocardium can appear normal 
with pure myocardial form of RCM. ◦ Pleural 
effusion and pericardial effusion may be present. • Functional findings (echocardiographic): 
◦ Severe LV diastolic dysfunction on Doppler 
echocardiography—restrictive LV filling with a 
peak velocity of early : late transmitral flow 
(E : A) ratio >2.0, short isovolumic relaxation 
time (<37 msec), shortened deceleration time of 
E (<45 msec), low peak velocity of mitral annular 
motion (E ′), and E : E ′ ≫15. ◦ Normal to low 
normal LV systolic function (in some cases LV 
systolic dysfunction is present). ◦ Regional wall 
motion abnormalities possible. ◦ Left atrial 
dysfunction. ◦ Severe left atrial appendage 
enlargement with evidence of blood stasis. 
◦ Midventricular obstruction with flow 
turbulence in cats with bridging endomyocar -
dial fibrosis. ◦ In cats with other causes of 
restrictive physiology, characteristics of the 
underlying disease can predominate; however, 
severe atrial enlargement and restrictive LV 
filling will be present in nearly all cats.
ECG
• Note: ECG findings are neither sensitive nor 
specific. • Sinus tachycardia is common, but 
cats with severe CHF and hypothermia may 
be bradycardic. • Ventricular or supraven -
tricular ectopic beats, paroxysmal or sustained 
supraventricular or ventricular tachycardia, or 
atrial fibrillation. • Atrial or ventricular 
enlargement patterns. • ST segment changes.
Pathology
• Note: histopathologic confirmation is 
needed to diagnose RCM. • Increased heart 
weight ( >19 g). • Severe biatrial dilatation. 
• Locally or diffusely thickened opaque 
endocardium. • False tendons (“moderator 
bands”) present in some cats. • Normal 
luminal size of the left and right ventricles. 
• Diffuse or focal cardiomyocyte disarray. 
• Increased interstitial and replacement 
fibrosis. • Abnormal intramural coronary 
arterioles with medial hypertrophy and 
narrowed lumen. • Increased number of 
inflammatory cells seen only in cats with acute 
endomyocarditis—this finding is commonly 
absent in cats with endocardial fibrosis.
  TREATMENT
• Patients with severe CHF are hospitalized 
for emergency care. • Mildly symptomatic 
animals can be treated with outpatient 
medical management.
• Cats with respiratory distress should receive 
oxygen. • Sedation is usually beneficial. 
• Thoracocentesis if relevant pleural effusion. 
• Maintain a low-stress environment (e.g., cage 
rest, minimize handling). • Heating pad for 
hypothermic patients. • Respiratory rate should 
be used to monitor immediate treatment success.

242  Blackwell’s Five-Minute Veterinary Consult  
CACTIVITY
Cage rest for CHF patients.
DIET
In acute heart failure, maintain intake with 
hand feeding if necessary.
Owner should be counseled regarding 
technique of pill administration in cats, 
possible adverse effects of medications, 
importance of maintaining stable food and 
water intake, and monitoring their cat’s 
resting respiratory rate at home.
Acute CHF
• Parenteral administration of furosemide 
(1–2 mg/kg IV/IM/SC q2–6h); CRI may be 
considered. • Dermal application of nitroglyc -
erin ointment (2%, one-fourth inch q12h). 
• Oxygen delivered by cage, mask, nasal 
prongs, or flow-by. • Thoracocentesis if 
relevant pleural effusion. • Dobutamine only if 
cats are hypotensive (systolic blood pressure 
<90 mmHg); 1–5  μg/kg/minute as CRI, start 
a lower dose and increase over 0.5–1h. 
• Severe supraventricular tachyarrhythmias can 
be treated with diltiazem CRI (2–6  μg/kg/min 
IV). • Ventricular tachycardia may resolve with 
resolution of CHF . • Acute therapy of 
ventricular tachycardia may include lidocaine 
(0.25–0.5 mg/kg IV slowly ); monitor closely 
for neurologic signs of toxicity. • Pimobendan 
(0.25 mg/kg PO q12h) may be helpful to 
increase cardiac performance in acute heart 
failure, but is only used in animals that cannot 
be stabilized and systemic hypotension cannot 
be corrected. Note: pimobendan is not 
approved for clinical use in cats and clinical 
safety and efficacy data are limited. 
• Antiplatelet medication (clopidogrel bisulfate 
18.75 mg PO q24h) or anticoagulants (e.g., 
unfractionated heparin 150–250 IU/kg SC 
q6h) may be administered, in particular in cats 
with severe left atrial enlargement and 
spontaneous echocardiographic contrast.
Chronic Therapy
• Furosemide is gradually decreased to lowest 
effective dose. • Angiotensin-converting 
enzyme (ACE) inhibitors may reduce fluid 
retention, decrease the need for diuretics, and 
counterbalance adverse effects of diuretics 
(e.g., enalapril 0.25–0.5 mg/kg PO q12–
24h). • Diltiazem (1.5–2.5 mg/kg regular 
diltiazem or 10 mg/kg q24h extended-release 
diltiazem) decreases heart rate and improves 
supraventricular arrhythmias in affected cats; 
the addition of digoxin (0.007 mg/kg PO q48h) may allow better control of ventricular 
response rate in cats with atrial fibrillation; 
cats with hemodynamically important 
ventricular and supraventricular ectopy can 
also benefit from sotalol (1.0–2.0 mg/kg PO 
q12h). • Pimobendan (0.25 mg/cat PO 
q12h) may be helpful in the management of 
chronic heart failure; note: pimobendan is not 
approved for clinical use in cats. • T reat 
associated conditions (e.g., dehydration, 
hypothermia, hypokalemia). • Clopidogrel 
(one-fourth of a 75 mg tablet PO q24h) to 
inhibit platelets chronically; aspirin (25 mg/
kg PO q72h) may also be considered, but 
efficacy is questionable; in cases of echogenic 
smoke or prior ATE, dual platelet inhibition 
(clopidogrel and aspirin) may be used. 
• Addition of low molecular weight heparin 
(enoxaparin [Lovenox®] at 1–2 mg/kg q12h 
SC) may be considered in cats at high risk for 
thromboembolic disease; apixaban (Eliquis®) 
at 0.625 mg/cat q12h in cats <5 kg body-
weight and 1.25 mg/cat q12h in cats ≥5 kg 
has been recommended, but published 
evidence is not available. • T reatment of cats 
with preclinical RCM has rarely been 
reported, but includes ACE inhibitors and 
antiplatelet drugs; there is currently no 
specific drug for LV diastolic dysfunction.
• Beta blockers should never be administered 
in cats with RCM. • For diltiazem—brady-
cardia, atrioventricular block, myocardial 
failure, and hypotension. • For furosemide—
severe dehydration, severe hypokalemia, and 
moderate to severe azotemia. • For ACE 
inhibitors—moderate to severe azotemia, 
hypotension, and hyperkalemia.
• Combination of ACE inhibitors and 
furosemide—hypotension and renal failure. 
• Chronic aspirin therapy may increase risk 
of renal side effects of ACE inhibitors and 
may lead to inappetence and gastrointestinal 
upset. • Combining antiplatelets and anti  - 
coagulants may increase risk of bleeding.
  FOLLOW-UP
• Frequent physical reexaminations to assess 
response to treatment. • Frequent reevalua-
tion of hydration status and renal function, 
particularly in first few days of therapy to 
avoid dehydration, hypokalemia, and 
azotemia. • Repeated thoracocentesis if 
necessary. • “Hands-off” hourly assessment of 
respiratory rate in first 12–24 hours can be 
used to monitor efficacy of CHF therapy. 
• Radiographs may be repeated in 12–24 hours to monitor pulmonary infiltrate 
resolution. • Repeat physical examination 
and analysis of blood biochemistries after 3–7 
days’ treatment of acute CHF . • Stable 
patients reevaluated every 2–4 months or 
more frequently if problems occur.
No known preventative measures for RCM.
Tissue necrosis or loss of function in limbs 
affected by thromboembolic complications, 
adverse effects of medications, sudden death, 
and euthanasia due to refractory heart failure.
Variable, but most cats have a grave 
Aortic thromboembolism and CHF .
Hyperthyroidism should be ruled out with 
appropriate testing in feline patients with 
heart disease ≥6 years of age.
SYNONYMS
• Intermediate cardiomyopathy. • Unclassified 
SEE ALSO
• Aortic Thromboembolism. • Congestive 
Heart Failure, Left-Sided. • Congestive Heart 
Failure, Right-Sided.
• A = peak velocity of late transmitral flow. 
• ATE = arterial thromboembolism. • CHF 
= congestive heart failure. • E = peak velocity 
of early transmitral flow. • E′ = peak velocity 
of mitral annular motion. • LV = left 
ventricular. • RCM = restrictive 
Charles PY, Li YJ, Nan CL, Huang XP . 
Insights into restrictive cardiomyopathy 
from clinical and animal studies. J Geriatr 
Cardiol 2011, 8:168–183.
Fox PR. Endomyocardial fibrosis and 
restrictive cardiomyopathy: pathologic and 
clinical features. J Vet Cardiol 2004, 
6:25–31.
Author  Karsten E. Schober
available onlineCardiomyopathy, Restrictive—Cats  (continued)

Canine and Feline, Seventh Edition  243
C
Cardiopulmonary Arrest
  BASICS
• Cessation of effective perfusion and 
ventilation because of loss of coordinated 
cardiac and respiratory function.
• Cardiac arrest invariably follows respiratory 
arrest if not recognized and corrected.
• Generalized or cellular hypoxia may be 
cause or effect of sudden death.
• After 1–4 minutes of airway obstruction, 
breathing efforts stop while circulation 
remains intact.
• If obstruction continues for 6–9 minutes, 
severe hypotension and bradycardia lead to 
dilated pupils, absence of heart sounds, and 
lack of palpable peripheral pulse.
• After 6–9 minutes, myocardial contractions 
cease even though ECG may look normal—
pulseless electrical activity (formerly electrical 
mechanical dissociation).
• Ventricular fibrillation, ventricular asystole, 
and pulseless electrical activity are rhythms 
indicating cessation of myocardial contractility.
• All systems are affected, but those requiring 
greatest supply of oxygen and nutrients 
affected first.
• Neurologic.
• Any age, breed, or sex.
SIGNS
• Lack of response to stimulation.
• Loss of consciousness.
• Agonal gasping or absence of ventilation.
• Absence of peripheral pulses.
• Absence of audible heart sounds.
CAUSES
• Hypoxemia caused by ventilation–perfusion 
mismatch, diffusion barrier impairment, hypo  - 
ventilation, or shunting.
• Poor oxygen delivery due to anemia or 
• Myocardial disease—infectious, inflammatory, 
infiltrative, traumatic, neoplastic, or embolic.
• Acid-base abnormalities.
• Electrolyte derangements—hyperkalemia, 
hypocalcemia, and hypomagnesemia.
• Hypovolemia.
• Shock.
• Anesthetic agents.
• Sepsis/septic shock.
• CNS trauma.
• Electrical shock.RISK FACTORS
• Cardiovascular disease.
• Respiratory disease.
• T rauma.
• Anesthesia.
• Septicemia.
• Endotoxemia.
• Ventricular arrhythmias—ventricular 
tachycardia, R on T phenomenon, multiform 
ventricular complexes.
• Increased parasympathetic tone—
gastrointestinal disease, respiratory disease, 
manipulation of eyes, larynx, or abdominal 
viscera.
• Prolonged seizing.
• Invasive cardiovascular manipulation—
pericardiocentesis, surgery, angiography.
  DIAGNOSIS
• Sudden cardiovascular collapse associated 
with inadequate cardiac output leading to 
severe consequences.
• Quick assessment and diagnosis are critical.
• Assess the ABCs—airway, breathing, circu  - 
lation.
• Severe hypovolemia and absence of palpable 
pulses.
• Pericardial effusion with cardiac tamponade, 
decreased cardiac output, and muffled heart 
sounds.
• Pleural effusion with respiratory arrest.
• Respiratory arrest can be confused with 
cardiopulmonary arrest (CPA).
• Upper airway obstruction can rapidly 
progress to CPA.
May help identify underlying cause for CPA, 
but should not be part of initial triage.
• Arterial blood gas evaluation may be useful 
during or after resuscitative procedures, but is 
not part of initial emergency management.
• Venous blood gas evaluation may be more 
useful during cardiopulmonary resuscitation 
(CPR) than arterial blood gas and provides 
electrolyte and lactate concentrations.
IMAGING
• Thoracic/abdominal focused assessment with 
sonography for trauma (TFAST®/AFAST®) 
may be useful in identifying underlying 
disease; additional terminology being 
introduced, such as POCUS (point of care 
ultrasound) and eFAST (extended FAST).
• Thoracic or abdominal radiographs or 
abdominal ultrasound may help identify 
underlying disease processes, but only 
consider after patient has been stabilized.
• Echocardiography may confirm pericardial 
effusion or underlying myocardial disease, but should not interfere with resuscitative 
procedures.
Once CPA has developed, continuous ECG 
monitoring, blood pressure monitoring, pulse 
oximetry, and capnography are useful in 
monitoring effectiveness of resuscitative 
  TREATMENT
Institute CPR immediately upon diagnosing 
CPA; CPR in veterinary patients should 
follow Reassessment Campaign on Veterinary 
Resuscitation (RECOVER) evidence-based 
guidelines, published in 2012 and divided 
into five domains. It is recommended the 
reader read the original publication.
Basic Life Support (Domain 2)
Immediate Recognition of CPA
If patient is identified as being nonresponsive 
and apneic, start CPR immediately, do not 
take time to confirm via palpation of pulse 
or ECG.
Chest Compressions
• Perform CPR in continuous, uninterrupted, 
2-minute cycles when possible.
• Use the cardiac pump in patients weighing 
<10 kg bodyweight; with the patient in right 
lateral recumbency, perform compressions 
directly over the heart (intercostal spaces 
3–5); this can be performed using one or 
two hands.
• Use the thoracic pump for patients 
weighing >10 kg bodyweight; with the 
patient in right lateral recumbency, apply 
thoracic compressions at the widest portion 
of the thorax.
• Different compression and ventilation 
regimes have been reported.
• Providing appropriate compressions 
(100–120 per minute) and appropriate 
ventilations (10 per minute) without stopping 
compressions for ventilations and without 
trying to synchronize ventilations with 
compressions is the goal; the chest should be 
displaced ∼30–50%.
• T ry to minimize discontinuing compressions 
to interpret ECG.
• Avoid leaning on the patient during chest 
compressions and allow full chest wall recoil.
• Interposing abdominal compressions 
between chest compressions enhances 
cerebral and coronary blood flow by 
increasing aortic diastolic pressure; this 
technique has not been shown to improve 
survival, but should be considered if 
adequate personnel are available.
Airway and Ventilation
• Visualize the airway by extending the 
patient’s head and neck and pulling the tongue 
forward; clear any debris (e.g., secretions,

244  Blackwell’s Five-Minute Veterinary Consult  
Cblood, or vomitus) manually or with suction; 
use of a laryngoscope is advised.
• Establish an airway by either oral endo -
tracheal intubation or, if complete 
obstruction, emergency tracheostomy.
• Correct endotracheal tube placement 
should be confirmed visually, by auscultation 
and/or capnography.
• 10 breaths per minute with a tidal volume 
of 10 mL/kg and an inspiratory time of 
1 second; peak airway pressures should not 
exceed 20 cm H2O.
• Techniques for ventilation include mouth 
to mouth, mouth to nose, or mouth to 
endotracheal tube; these techniques provide 
∼16% oxygen; use of a mechanical 
resuscitator (Ambu® bag) and room air 
provides 21% oxygen.
• The preferred technique is endotracheal 
intubation and ventilation with 100% 
oxygen using an Ambu bag or an anesthesia 
machine.
• The suggested rate of oxygen administration 
is 150 mL/kg/minute.
Circulation
• Assessment—palpate peripheral pulses and 
auscultate heart to confirm CPA.
• External thoracic compression provides at 
best ∼30% of normal cardiac output; internal 
cardiac compression is two to three times 
more effective in improving cerebral and 
coronary perfusion.
Open-Chest CPR
• Indicated if closed-chest CPR is ineffective 
or preexisting conditions such as flail chest, 
obesity, diaphragmatic hernia, pericardial 
effusion, or other significant intrathoracic 
disease preclude closed-chest techniques.
• Perform through a left thoracotomy at the 
fifth or sixth intercostal space.
• Perform a pericardectomy.
• The palmar surface of the fingers and 
thumb is used to push the ventricular blood 
toward the great vessel; digital compression of 
the descending aorta may help improve 
coronary and cerebral perfusion.
Advanced Life Support (Domain 4)
This includes drug therapy and additional 
resuscitation techniques. Drugs should be 
administered every other CPR cycle 
(~q4 minutes).
Epinephrine
• Epinephrine low dose—0.01 mg/kg IV 
(1 : 10,000) 1 mL/10 kg patient.
• Epinephrine high dose—0.1 mg/kg IV 
(1 : 1000) can be used in protracted CPR.Vasopressin
May be used as alternative to epinephrine 
0.8 U/kg IV (20 U/ml; ~0.5 ml/10 kg 
patient); may be used in combination with 
epinephrine, especially if protracted CPR.
Atropine
• Atropine—0.04 mg/kg IV (0.4 mg/mL) 
1 mL/10 kg patient.
• Limited data to suggest benefit unless arrest 
is due to increased vagal tone.
Fluids
Administer fluids cautiously unless known 
hypovolemia has led to CPA. Crystalloids, 
colloids, or blood products may be consid-
ered, including Oxyglobin®.
• See Advanced Life Support.
• Administer drugs via intravenous, intra  - 
osseous, or intratracheal routes in descending 
order of preference; volumes should be 
doubled if administering via the intratracheal 
route and diluted in saline.
• Intracardiac administration should not be 
used unless open-chest CPR is being performed; 
administration of epinephrine into the left 
ventricle with concurrent digital or mechanical 
compression of descending aorta is optimal.
Fluid administration should be used cautiously 
and only if there is a known history of hypo-  
volemia; excessive fluid administration may 
lead to decreased coronary perfusion.
  FOLLOW-UP
• Maintain normal heart rate and blood 
pressure with fluids and inotropic agents.
• Arterial blood pressure.
• Central venous pressure.
• Blood gas analysis.
• Support respiration with artificial 
ventilation and supplemental oxygen.
• Neurologic status—if signs of increased 
intracranial pressure develop, consider 
mannitol, corticosteroids, and furosemide.
• ECG—continuously.
• Urine output.
• Body temperature.
• Radiograph thorax to assess resuscitative 
injury.• Diagnose and correct factors that led to 
initial CPA.
Careful monitoring of all critically ill patients.
• Aspiration pneumonia.
• Fractured ribs or sternebrae.
• Pulmonary contusions and edema.
• Pneumothorax.
• Neurologic deficits.
• Cardiac arrhythmias.
• Prognosis depends on underlying disease 
process.
• Rapid return to spontaneous cardiac and 
respiratory function improves the prognosis.
• Overall prognosis is poor; <10% of patients 
are discharged.
None
SYNONYMS
• For CPA—cardiac arrest, heart attack.
• For CPR—cardiopulmonary cerebral 
resuscitation (CPCR).
SEE ALSO
• Ventricular Fibrillation.
• Ventricular Standstill (Asystole).
• CPA = cardiopulmonary arrest.
• CPCR = cardiopulmonary cerebral 
resuscitation.
• CPR = cardiopulmonary resuscitation.
• FAST = focused assessment with 
sonography for trauma.
• POCUS = point of care ultrasound.
• RECOVER = Reassessment Campaign on 
Veterinary Resuscitation.
Fletcher DJ, Boller M, Brainard BM, et al. 
RECOVER evidence and knowledge gap 
analysis on veterinary CPR. Part 7: Clinical 
guidelines. J Vet Emerg Crit Care 2012, 
22(S1):102–131.
McIntyre RL, Hopper K, Epstein SE, et al. 
Assessment of cardiopulmonary resuscita-
tion in 121 dogs and 30 cats at a university 
teaching hospital (2009–2012). J Vet Emerg 
Crit Care 2014, 24(6):693–704.
Consulting Editor  Michael AherneCardiopulmonary Arrest  (continued)

Canine and Feline, Seventh Edition  245
C
Cataracts
  BASICS
Opacification of the lens (focal or diffuse).
• The normal lens is composed of perfectly 
aligned lens fibers that create a transparent 
structure. A clear capsule surrounds the cortex 
and nucleus. New lens fibers are continually 
produced at the equator of the lens cortex 
throughout life. The aqueous humor provides 
nutrition to the lens.
• A cataract occurs when there is derange­
ment of lens fibers due to changes in lens 
nutrition, energy metabolism, protein 
synthesis or metabolism, or osmotic balance.
• Anterior uveitis is a common cause of 
altered lens nutrition.
• Genetics can result in altered protein and 
energy metabolism, or protein synthesis, in 
the lens.
• Diabetes mellitus affects the osmotic 
balance in the lens. Hyperglycemia increases 
glucose in the aqueous and lens overwhelming 
the glycolysis pathway; glucose is shunted to 
the sorbitol pathway; sorbitol creates an 
osmotic gradient that draws water into the 
lens and rapid cataract formation. The 
sorbitol pathway requires aldose reductase 
enzyme and dogs have more aldose reductase 
than cats, making cats more resistant to 
developing diabetic cataracts. The enzyme 
levels vary between individuals, which may 
explain dogs that are resistant to cataract 
development.
GENETICS
• Inheritance has been established for many 
dog breeds; the most common mode of 
inheritance is autosomal recessive.
• Inheritance has been established in the 
Himalayan cat (autosomal recessive).
• One of the leading causes of blindness in 
dogs.
• The prevalence of genetic cataracts varies 
significantly; up to 10% in some breeds.
• Most diabetic dogs will develop cataracts 
regardless of their diabetic control.
• Cataracts are rare in cats.
Species
Over 135 dog breeds are suspected as being 
predisposed to hereditary cataracts.
Cataracts can develop at any age; genetic 
cataracts can develop as early as 6 months of age.SIGNS
• Cloudy/white appearance of the lens.
• Vision loss when the cataracts are bilateral 
and diabetic cataracts with a rapid, bilateral 
onset.
• Polyuria/polydipsia is noticed prior to 
cataract development in diabetic dogs.
• General physical examination findings—
unremarkable unless the dog is an 
undiagnosed diabetic.
• Ophthalmic examination findings—
opacification in one or both lenses.
 ∘Incipient stage—small, focal opacity/
opacities in the lens that does not interfere 
with the view of the fundus; no vision 
deficits.
 ∘Immature stage—diffusely cloudy 
appearance to the lens with the tapetal 
reflection still visible and some portions of 
the fundus visible through a dilated pupil; 
the menace reflex is positive.
 ∘Mature stage—completely opaque lens 
with no tapetal reflection visible; blind.
 ∘Hypermature stage—wrinkled lens 
capsule, areas of dense white mineraliz­
ation, may have portions of liquefied cortex 
(white, sparkly to clear); deep anterior 
chamber; blind unless there is a large area 
of clear liquefied cortex.
 ∘Intumescent mature cataract—opaque, 
swollen lens usually due to the hyper­
osmotic effect of diabetes; shallow anterior 
chamber.
CAUSES
• Hereditary—most common cause in dogs.
• Diabetes mellitus.
• Anterior uveitis—either by altered nutrition of 
the lens from the abnormal aqueous, or by 
posterior synechia and inflammatory debris 
causing opacification of the anterior lens capsule.
• T rauma—perforating injury that disrupts the 
anterior lens capsule, most commonly a cat 
claw injury, especially in puppies and kittens.
• Senile—slowly progressive cataract in 
geriatric animals, usually beginning as dense 
nuclear sclerosis followed by gradual 
spoke ­like opacities extending into the cortex.
• Congenital—due to heredity, in utero 
insult, or associated with other congenital 
ocular anomalies such as persistent pupillary 
membranes, persistent hyperplastic primary 
vitreous/persistent tunica vasculosa lentis, or a 
hyaloid artery attachment.
• Surgery—transpupillary laser energy, 
intraocular instrument trauma.
• Toxic—long ­term ketoconazole therapy; 
suspected secondary to toxic by ­products of 
degenerating photoreceptors in dogs with 
progressive retinal atrophy.
• Radiation—when the eye is in the radiation 
treatment field for neoplasia of the mouth or 
head.• Hypocalcemia—can cause bilateral, diffuse 
punctate or incipient cataracts.
• Nutritional—use of unbalanced milk 
replacers in bottle ­fed puppies and kittens.
• Electrical shock—chewing electrical cords 
or lightning strike.
• Diabetes mellitus (dogs).
• Chronic anterior uveitis.
• Progressive retinal atrophy.
  DIAGNOSIS
Lenticular nuclear sclerosis—normal aging 
change in the lens of dogs and cats starting 
at 6 years of age due to compression of 
older lens fibers in the center of the lens; 
gradually becomes more visible with age 
and can be mistaken for a cataract in 
geriatric patients; definitive diagnosis can 
be made using mydriasis (1% tropicamide) 
and the observation of a perfectly round, 
bilaterally symmetric, homogeneous nucleus 
in the center of each lens, and the ability to 
view the fundus through the lens; vision is 
rarely affected and treatment is not indicated.
Dogs with diabetic cataracts may have 
hyperglycemia and glucosuria.
IMAGING
Ocular ultrasound can be used to evaluate the 
posterior lens capsule for any sign of rupture 
and can evaluate for retinal detachment prior 
to cataract surgery.
ERG is performed prior to cataract surgery to 
evaluate for retinal degeneration when the 
fundus is not visible due to the cataract.
  TREATMENT
ACTIVITY
For safety, blind animals should not be 
allowed access to an in ­ground swimming 
pool or elevated decks with open railings; use 
caution near stairs; restrict outside activity to 
fenced yards or leash walks.
• Cataract surgery is routinely performed, 
with an overall 80–90% success rate.
• Once the cataracts are removed they cannot 
return.
• Artificial lens implants will restore essentially 
normal vision.
• Evaluation for surgery should be done early 
in the course of cataract development to avoid 
complications that may result in the cataract 
becoming inoperable, to allow time to plan

246  Blackwell’s Five-Minute Veterinary Consult  
Cfor the surgery, and in some cases to eliminate 
the need and extra cost for an ocular ultra  ­ 
sound and ERG.
• Phacoemulsification (removal of the 
cataract through a corneal incision using 
ultrasonic waves to emulsify and aspirate the 
lens) is the most common technique for 
cataract removal.
• The ideal time for cataract surgery is the 
immature/early mature stage.
• Inherited, diabetic, and senile cataracts are 
potentially good candidates for surgery; 
cataracts secondary to anterior uveitis are 
normally poor surgical candidates.
• Artificial intraocular lenses are routinely 
placed inside the patient’s lens capsule; lens 
implants restore normal focus and help 
minimize posterior capsular fibrosis; if a lens 
cannot be implanted (e.g., due to an unstable 
lens capsule or luxated lens), the dog or cat 
will still have functional vision.
• T raumatic lens perforation with release of 
lens cortex into the anterior chamber may 
require surgery to remove the lens, depending 
on the size of the capsular tear.
• Topical anti ­inflammatory medication is 
recommended q6–24h to help prevent or 
treat lens ­induced uveitis with immature, 
mature, and hypermature cataracts; this 
can be a topical nonsteroidal anti ­
inflammatory drug (NSAID) such as 
flurbiprofen, diclofenac, or ketorolac, or a 
topical steroid such as prednisolone acetate 
1% or dexamethasone 0.1%; topical 
NSAIDs may be preferable in diabetic 
patients.
• Topical atropine q8–24h is indicated for 
lens­induced uveitis; contraindicated with 
glaucoma .
• Oral NSAIDs (carprofen, meloxicam, 
deracoxib) are also used to treat lens ­induced 
uveitis.
• Topical antioxidants are advertised as able 
to reverse cataract changes; to date there have been no published data conclusively showing 
a significant reversal, or delay in progression; 
time spent trying medical therapy will delay 
evaluation for surgery, resulting in surgery 
being performed at a suboptimal stage, or 
complications from the cataract making it 
inoperable.
• A topical aldose reductase inhibitor, 
Kinostat®, is in the final stage of FDA 
approval. When made available, it may prove 
helpful in delaying the onset of diabetic 
cataracts in dogs.
  FOLLOW-UP
• Incipient or early immature cataracts 
should be monitored regularly for progression 
in order to select the ideal time for surgery 
and to avoid complications associated with 
cataracts.
• Postoperative monitoring by the surgeon is 
critical for the success of surgery and should 
be clearly discussed with the owner prior to 
surgery.
Do not breed animals with cataracts.
• Lens­induced uveitis—associated with 
hypermature cataracts and cataracts that 
progress rapidly; caused by antigenic lens 
proteins leaking through the lens capsule. 
Clinical signs can be subtle (e.g., low 
intraocular pressure) to extreme (granulo­
matous uveitis with aqueous flare, miosis, 
synechia, keratic precipitates); preoperative 
uveitis increases postoperative complications.
• Secondary glaucoma—impaired aqueous 
outflow from intraocular changes associated 
with lens ­induced uveitis, or from an 
intumescent cataract causing a forward 
displacement of the iris, narrowing the 
iridocorneal angle.
• Retinal detachment—associated with hyper  ­ 
mature cataracts and cataracts in young dogs 
with a rapid onset and cortical liquefaction.
• Lens luxation—associated with hypermature 
cataracts in which the lens and capsule shrink, causing the zonules to stretch and break, 
resulting in a lens subluxation or luxation.
• Most cataracts are progressive, although the 
rate of progression can vary widely depending 
on age, breed, and location of the cataract.
• Long ­term prognosis following cataract 
surgery is very good; however, some patients 
have increased risk for postoperative 
• Those that do not pursue surgery should be 
monitored for uveitis and glaucoma.
• Retinal detachment.
• Lens­induced uveitis.
• Congenital ocular anomalies.
• Immediate referral for cataracts in young 
dogs (<2 years of age) is recommended 
because the cataract can progress very rapidly, 
with partial cortical liquefaction followed by 
• Nuclear sclerosis is prominent in geriatric 
animals; a dilated exam may be necessary to 
definitively distinguish nuclear sclerosis from 
cataract.
SEE ALSO
Cats.
Dogs
ABBREVIATION
drug.
Author  Margi A. Gilmour
available onlineCataracts  (continued)

Canine and Feline, Seventh Edition  247
C
Cerebellar Degeneration
  BASICS
OVERVIEW
• Progressive and non-progressive etiologies.  
Progressive - premature aging and neuronal 
death; may be due to failure of neuronal 
energy supply, ion regulation, excitotoxicity, 
autoimmunity/inflammation, or inappropriate 
apoptosis; neonatal, postnatal, and adult onset 
(rare). •  Nonprogressive - due to abnormal 
cerebellar development following in utero or 
neonatal viral infection in cats (feline panleuko  - 
penia) and dogs (canine herpesvirus, canine 
parvovirus).
Progressive
• Dog and cat. • Described in over 40 dog 
breeds, often affecting a single family or 
individual. • Eight causal mutations, all with 
autosomal recessive mode of inheritance, have 
been identified. Beagle (onset of clinical signs 
before 1 month); Finnish hound (2 months), 
Parson Russell terrier (2 months), Jack Russell 
terrier (2–12 months) Hungarian Vizsla (3 
months); Kerry blue terrier and Chinese 
crested (3–4 months); Old English sheepdog 
and Gordon setter (6 months – 3 years). 
• Immune-mediated disorder described in 
Coton de T ulear (2 months). • Sporadic 
reports in miniature poodle (neonatal), 
papillon (5 months); Scottish terrier, Border 
Collie, Lagotto Romagnolo, Australian 
Kelpie, Labrador Retriever, Bavarian 
mountain dogs, Italian hound (2 months –  
1 year); English bulldog (5–8 months); 
American Staffordshire terrier (2–9 years). 
• Late onset disorder described in Labrador 
Retriever, Bern running dog, Irish setter, and 
Brittany spaniel (signs at 5–13 years). 
• Cerebellar degeneration and coat color 
dilution reported in one family of Rhodesian 
ridgebacks. • X-linked mode of inheritance 
suspected in English pointer (only males 
affected). • Both early- (days to weeks) and 
late- (years) onset in domestic shorthair cat. 
• Described in two Havana brown kittens 
from the same litter. Signs observed at one 
month. Heritable nature suspected.
Nonprogressive
• T wo causal mutations identified in two dog 
breeds. • Non-inflammatory disorder with 
autosomal recessive mode of inheritance 
reported in six litters of Coton de T ulear (signs 
by 2 weeks). • Eurasier dog (2 months).
SIGNS
• Cerebellar ataxia- hypermetria; broad-based 
stance; swaying of body, intention tremors. 
• Lack of menace responses with normal 
vision and pupillary light reflexes. • Head tilt 
and episodes of vestibular ataxia with resting 
or positional nystagmus. • Diffuse tapetal hyperreflectivity on funduscopic exam. 
• Decerebellate posture—opisthotonos with 
extensor rigidity of the forelimbs and flexed 
hind limbs. • Cerebellar degeneration is not 
characterized by altered mentation, proprio -
ceptive deficits, or paresis. • Progression of 
signs varies. • Use caution in interpreting 
progression of clinical signs—cerebellar 
ataxia in a puppy or kitten with cerebellar 
degeneration caused by in utero or neonatal 
infection may appear to worsen as the animal 
grows and becomes more active; the 
underlying disease process itself is 
nonprogressive.
• Causal mutations associated with progressive 
cerebellar degeneration have been identified 
in several breeds. • In utero or neonatal 
exposure to feline panleukopenia or canine 
herpesvirus infection. • Poor vaccination 
history or exposure to modified live virus 
during gestation. • A syndrome of hepato-
cerebellar degeneration has been described in 
a litter of Bernese mountain dogs. 
• Paraneoplastic cerebellar degeneration has 
been reported in humans.
  DIAGNOSIS
• Lysosomal storage diseases—diffuse diseases 
of the CNS; differentiate by presence of 
signs of involvement of parts of the CNS 
outside of the cerebellum. • Toxicity (e.g., 
hexachlorophene)—differentiate by history of 
exposure. • Inflammatory diseases—infectious 
(e.g., canine distemper and feline infectious 
peritonitis [FIP]) and immune-mediated 
(dogs). Differentiate from cerebellar 
degeneration by MRI and cerebrospinal fluid 
(CSF) analysis. Infectious diseases are 
frequently accompanied or preceded by 
systemic signs of illness. • Cerebellar cyst— 
differentiate by advanced imaging (MRI). 
• Medulloblastoma (cerebellar tumor)—
reported in dogs and cats <1 year old; 
differentiate by advanced imaging (MRI) and 
CSF analysis. • Other primary and metastatic 
tumors in adult dogs.
IMAGING
• MRI is preferred imaging modality—
cerebellum may be smaller than normal. 
• CT can aid in diagnosis of other conditions 
(e.g., cyst); if MRI is not accessible, CT may 
have some value.
• CSF analysis—normal with nonprogressive 
disease; normal-to-high protein concentration 
and normal cell counts with progressive disease.
• Cerebellar biopsy—may be only definitive 
means of antemortem diagnosis.  TREATMENT
• Restrict to supervised activity in safe areas; 
leash-walks only; avoid stairs, furniture, 
proximity to swimming pools, etc.
• Amantadine has potentiating effects on 
dopaminergic neurotransmission in CNS and 
anticholinergic activity; buspirone is serotonin 
agonist; research models demonstrate some 
potential benefit for progressive cerebellar 
degeneration; guidelines and clinical evidence 
are lacking. • Neuroprotective agents (such as 
coenzyme Q10 and acetyl-L-carnitine) may 
have promising effects.
N/A
  FOLLOW-UP
• Neurologic status—examine at weekly-to-
monthly intervals if progression of signs is 
uncertain; consider videotaping patient to 
determine progression objectively. 
• Progression of signs—rate varies depending 
on etiology; ranges from days to years. 
• Nonprogressive disease—patient may show 
improvements as they learn to compensate for 
deficits. • Do not vaccinate pregnant animals 
with modified live virus. • Do not breed 
animals with familial history of cerebellar 
disease.
de Lahunta A, Glass E, Kent M. Cerebellum. 
In: de Lahunta A, Glass E, eds., Veterinary 
Neuroanatomy and Clinical Neurology, 4th 
ed. St. Louis, MO: W.B. Saunders, 2015, 
pp. 368–408.
Dewey CW, da Costa RC. A Practical Guide 
to Canine and Feline Neurology, 3rd ed. 
Ames, IA: Wiley-Blackwell, 2016, 
pp. 183–191.
Urkasemsin, G, Nielsen DM, Singleton A, 
et al. Genetics of hereditary ataxia in 
Scottish Terriers. J Vet Intern Med, 2017, 
31(4):1132–1139.
Authors  Richard J. Joseph and Anne 
E. Buglione

248  Blackwell’s Five-Minute Veterinary Consult  
C
  BASICS
OVERVIEW
Caused by incomplete development of parts 
of the cerebellum owing to intrinsic (inherited) 
or extrinsic (infectious, toxic, or nutritional) 
factors.
• Symptoms may not be visible until puppies 
and kittens begin to stand/walk (usually by 
6 weeks old).
• Hereditary in Airedale, chow chow, Boston 
terrier, Labrador retriever, Weimaraner, shih 
tzu, miniature schnauzer, and bull terrier.
SIGNS
• Symmetric, nonprogressive cerebellar 
disorder—head bobbing; limb tremors; 
aggravated by movement or eating and 
disappear during sleep (intention tremors).
• Cerebellar ataxia, wide-base stance.
• Dysmetria and disequilibrium—falling, 
flipping over.
• Cats—usually transplacental or perinatal 
infection with panleukopenia virus (wild or 
from modified live virus used in some 
vaccines), which selectively attacks rapidly 
dividing cells, e.g., external germinal layer of 
the cerebellum at birth and for 2 weeks 
postnatal.
• Dogs—hereditary in some breeds (autosomal 
recessive).
  DIAGNOSIS
• Age, breed, history, typical symmetric and 
nonprogressive symptoms—usually sufficient 
for tentative diagnosis.
• Early cerebellar abiotrophy—postnatal 
degeneration after normal development; slow 
progression of signs over weeks to months; 
neonatal onset (beagle, Samoyed, Rhodesian 
ridgeback, Irish setter, Jack Russell terrier, 
miniature poodle) or postnatal onset 
(Australian kelpie at 5–6 weeks; Kerry blue 
terrier at 8–16 weeks; rough-coated collie at 
4–8 weeks; bullmastiff at 4–9 weeks).
• Neuroaxonal dystrophy—slowly progressive 
cerebellar signs starting around 5 weeks of age 
in cats and 7 weeks in Chihuahuas.
• Cerebellar sequels of systemic canine herpes  - 
virus infection—follow systemic illness.
• Concomitant seizures or other cerebral 
signs—suggest other malformations, such as 
lissencephaly (wirehaired fox terrier and Irish 
setter) or hydrocephalus.• Final diagnosis possible only at necropsy.
IMAGING
MRI—cerebellar atrophy or malformation 
(incomplete or asymmetric filling of the 
caudal cranial fossa by the cerebellum); rule 
out other malformations.
• Cerebellum—normally very small in 
newborn kitten or puppy (cerebellar 
development continues for up to 10 weeks 
postnatal); subtle to marked atrophy; as 
necropsy is performed weeks to months after 
birth, there is no sign of active inflammation.
• T ransverse fibers of the pons—decreased 
size associated with marked cortical cerebellar 
atrophy.
• Hydrocephalus—may be concomitant, 
resulting from multifocal inflammation or 
multiple malformations (e.g., Dandy–Walker 
syndrome).
• Microscopic—depletion of cerebellar cortex 
cellular layers.
  TREATMENT
None
N/A
N/A
  FOLLOW-UP
Helps confirm the diagnosis (as necessary).
Avoid using modified live panleukopenia 
vaccines in reproducing female cats and keep 
cats vaccinated against panleukopenia.
N/A
• Slight improvement may occur as patient 
compensates for deficits.
• Deficits—permanent; do not progress; 
compatible with a normal lifespan.
• Some patients may be acceptable indoor 
pets.Care
• Restrict environment to prevent injuries 
and road accidents—no climbing, falling, or 
escaping.
• Nutritional support as needed.
• Euthanasia—severely affected animals that 
are unable to feed, groom, or be housetrained.
de Lahunta A, Glass E, Kent M. Veterinary 
Neuroanatomy and Clinical Neurology, 
4th ed. St. Louis, MO: W.B. Saunders, 
2015, pp. 389–390.
Author  Christine F . Berthelin-BakerCerebellar Hypoplasia

Canine and Feline, Seventh Edition  249
CCerebrovascular Accidents
  BASICS
• Sudden onset of nonprogressive focal brain 
signs. • Signs must remain for >24 hours for 
a diagnosis of cerebrovascular accident (CVA). 
• Permanent brain damage usually ensues. 
• Called transient ischemic attack or TIA if 
clinical signs resolve within 24 hours.
• Cerebrovascular diseases are the underlying 
cause of CVA. • Brain abnormality resulting 
from a pathologic process that compromises 
the blood supply to the brain. • Lesions 
affecting the cerebral blood vessels are divided 
into two broad categories: ◦ Hemorrhagic 
stroke—ruptured blood vessel with hemor­
rhage into or around the brain. ◦ Ischemic 
stroke—abrupt disruption of blood flow from 
blockage of an artery depriving the brain 
tissue of oxygen and glucose.
• Nervous. • Multisystemic—if underlying 
cause present.
Unknown; supposed low compared to human.
Species
• Ischemic stroke—cavalier King Charles 
spaniel and greyhound seem predisposed; 
small breed (≤15 kg) more likely to have 
cerebellar infarct; large breed (>15 kg) more 
likely to have midbrain or thalamic infarct. 
• Hemorrhagic stroke—unknown.
SIGNS
• Ischemic stroke—peracute to acute 
nonprogressive focal brain signs. • Hemorrhagic 
stroke—acute to subacute focal or multifocal 
brain signs that can progress over a short 
period of time.
• Fundus examination—may reveal tortuous 
vessels (systemic hypertension), hemorrhage 
(coagulopathy or systemic hypertension), or 
papilledema (elevated intracranial pressure 
[ICP]). • Coagulation defects—may underlie 
hemorrhagic stroke and cause hemorrhage in 
any tissue or organ and anemia.
• Ischemic stroke—signs depend on the 
localization of the vascular insult (prosence­
phalon, midbrain, pons, medulla, cerebellum). 
• Hemorrhagic stroke—signs relate to 
increased ICP with nonspecific forebrain and/
or brainstem disturbance.CAUSES
Ischemic Stroke
Dogs
• Unknown in 50% of cases. • Endocrine 
diseases—hyperadrenocorticism, hypothyroidism, 
diabetes. • Embolism, thromboembolism—
neoplastic (hemangiosarcoma, lymphoma), 
infectious (associated with bacterial 
endocarditis or other sources of infection), 
and aortic or cardiac. • Systemic 
hypertension—chronic kidney disease, protein 
losing enteropathy. • Fibrocartilaginous 
embolism. • Intravascular lymphoma. 
• Parasite migration ( Cuterebra ) or embolism 
(Dirofilaria immitis ).
Cats
• High likelihood of concurrent disease. 
• Parasite migration ( Cuterebra  or 
heartworms). • Systemic hypertension—
hyperthyroidism, chronic kidney disease, 
heart disease. • Neoplastic embolism. 
• Intracranial telangiectasia. • Hypertropic 
cardiomyopathy. • Hyperthyroidism. 
• Pulmonary disease. • Liver disease. 
• Neoplasia elsewhere in the body.
Hemorrhagic Stroke
Dogs
• Ruptured congenital vascular anomalies. 
• Primary and secondary brain tumors. 
• Inflammatory disease of arteries and veins 
(vasculitis). • Intravascular lymphoma. 
• Brain hemorrhagic infarction. • Impaired 
Cats
(vasculitis). • Brain hemorrhagic infarction. 
• Impaired coagulation—cerebral amyloid 
angiopathy. • Systemic hypertension.
• Ischemic stroke—systemic hypertension, 
systemic conditions associated with hyper  ­ 
coagulability syndrome. • Hemorrhagic 
stroke—systemic hypertension, 
coagulopathy.
  DIAGNOSIS
• Head trauma—history and physical 
findings suggestive of trauma. 
• Decompensation from primary or meta ­ 
static brain tumor—signs are progressive. 
• Infectious and noninfectious encephalitis—
acute to subacute clinical signs that gradually 
worsen. • Neurotoxicity—bilateral, symmetric 
neurologic deficits.
Most often normal; may show changes 
reflecting underlying cause.OTHER LABORATORY TESTS
• Cerebrospinal fluid—unlikely to confirm 
CVA, may help rule out inflammatory CNS 
disease. Variable findings; either normal, or mild 
mononuclear or neutrophilic pleocytosis; protein 
concentration occasionally elevated. 
• Prothrombin time—screening test for extrinsic 
mechanism defects. • Activated partial thrombo  ­ 
plastin time—screening test for intrinsic 
mechanism defects. • Bleeding time—prolonged 
in patients with von Willebrand’s disease; normal 
with most other coagulation defects, except 
disseminated intravascular coagulation. 
• Thromboelastography, D ­dimer assay, and 
antithrombin III—screening tests for hypercoag­
ulability syndrome as possible cause of ischemic 
stroke. • Endocrine testing—hyperadreno­
corticism, thyroid disease, and pheochro­
mocytoma. • Renal disease—urine protein/
creatinine ratio.
IMAGING
• CT—often normal during acute phase. 
• MRI—within 12–24 hours of onset to 
distinguish hemorrhage from infarction; 
T2­weighted and fluid ­attenuated inversion 
recovery (FLAIR) images particularly useful; 
T2*­weighted (gradient echo) images to show 
presence of or exclude intracranial hemorrhage; 
diffusion ­weighted imaging (DWI) sequence: 
ideal for identification of hyperacute stroke, 
excluding stroke mimics; perfusion ­weighted 
MRI can be used to depict brain regions of 
hypoperfusion and derive the tissue at risk by 
comparing the results with the findings on 
DWI. • Time of flight magnetic resonance 
angiography (MRA) and contrast ­enhanced 
MRA can be used to assess intracranial 
vascular status of stroke patients.
• CT—very sensitive for detection of 
acute hemorrhage; hyperdensity due to 
hyperattenuation of X ­ray beam by the globin 
portion of blood; attenuation decreases until 
the hematoma is isodense at about 1 month 
from onset; periphery of hematoma contrast ­
enhances from 6 days to 6 weeks after onset 
due to revascularization. • MRI—signal 
intensity of intracranial hemorrhage is 
influenced by several intrinsic (time from ictus, 
source, size and location of hemorrhage) and 
extrinsic (pulse sequence and field strength) 
factors; as hematoma ages, oxyhemoglobin in 
blood breaks down sequentially into several 
paramagnetic products (deoxyhemoglobin, 
methemoglobin, hemosiderin), each with 
different MRI signal intensities; compared to 
other conventional sequences, T2* ­weighted 
(gradient echo) images demonstrate readily 
detectable hypointensity regardless of time 
from ictus, source and location of hemorrhage, 
or field strength. • Multiple hemorrhagic 
lesions <5 mm—most often associated with 
hyperadrenocorticism, hypertension, chronic

250  Blackwell’s Five-Minute Veterinary Consult  
Ckidney disease, or hypothyroidism. • Single 
hemorrhagic lesion—most often associated 
with Angiostrongylus vasorum . • Multiple 
hemorrhagic lesions ≥5 mm—most often 
associated with Angiostrongylus vasorum , 
primary extracranial neoplasia with metastases 
(haemangiosarcoma).
Diagnosis of potential underlying causes.
Evaluate for hypertension (and potential 
underlying causes), endocrine disease 
(hyperadrenocorticism, hypothyroidism, 
hyperthyroidism, diabetes mellitus), chronic 
kidney disease (especially protein ­losing 
nephropathy), protein ­losing enteropathy, 
heart disease, and metastatic diseases 
(particularly hemangiosarcoma).
Evaluate for coagulopathy (and potential 
underlying causes), hypertension (and 
potential underlying causes), and metastatic 
diseases (particularly hemangiosarcoma).
• Ischemic necrosis centered on gray matter 
due to selective vulnerability. • Lesions limited 
to brain area vascularized by the affected vessel 
with sharply demarcated borders; normal 
surrounding brain tissue; minimal to no mass 
effect. • Global brain ischemia usually affects a 
dense area of selectively vulnerable neurons; 
specific anatomic areas including cerebral 
cortex, hippocampus, certain basal nuclei (e.g., 
caudate nuclei), thalamus, and cerebellar 
Purkinje cell layers are more susceptible to 
hypoxic injury. • Early ischemic cell changes 
occur rapidly and are a result of energy 
deprivation with swelling of the mitochondria 
and endoplasmic reticulum, which causes 
cytoplasmic microvacuolation; more chronic 
lesions are characterized by postnecrotic 
atrophy of the brain parenchyma, endothelial 
proliferation in viable capillaries, and 
accumulation of Gitter cells.
• Parenchymal bleeding results from rupture 
of the small penetrating brain arteries; most 
acute cases reveal fresh hemorrhage and acute 
neuronal necrosis that is slowly removed by 
macrophages, leaving over time a cystic cavity 
lined by fibrillary astrocytes. • Histology is 
characterized by presence of edema, neuronal 
damage, macrophages, and neutrophils in the 
region surrounding the hematoma. • While 
some cerebral hemorrhages stop quickly as a 
result of clotting and tamponade by the 
surrounding regions, others tend to expand 
over time; the latter is a result of continued 
bleeding from the primary source and to the 
mechanical disruption of surrounding vessels; the hemorrhage spreads between planes of 
white matter cleavage with minimal 
destruction, leaving nests of intact neural 
tissue within and surrounding the hematoma.
  TREATMENT
• Monitoring and correction of basic physiologic 
variables (e.g., oxygen level, fluid balance, blood 
pressure, body temperature). • Maintenance of 
systemic arterial blood pressure within physiologic 
range; aggressive lowering of blood pressure 
should be avoided during acute stages unless the 
patient is at high risk of end ­stage organ damage 
(systolic blood pressures >180 mmHg); 
hypertension can develop as a physiologic 
response to a stroke to ensure adequate cerebral 
perfusion pressure; elevated blood pressure can 
persist for up to 72 hours after the onset of injury. 
• No evidence that glucocorticoid provides 
beneficial neuroprotection; most neuroprotective 
agents tested have either failed to prove their 
efficacy in clinical trials or are awaiting further 
investigation.
• Patient stabilization (airway protection, 
monitoring and correction of vital signs). 
• Assessment and monitoring of neurologic 
status. • Determination and treatment of 
potential underlying causes of hemorrhage. 
• Assessment for the need of specific treatment 
measures including management of raised ICP , 
which revolves around reducing cerebral 
edema, optimizing cerebral blood volume, and 
eliminating space ­occupying mass. • Risk of 
neurologic deterioration and cardiovascular 
instability highest during the first 24 hours 
after onset of intracranial hemorrhage, as the 
space ­occupying lesion slowly expands and 
cerebral vasogenic edema develops.
• Antihypertensive—consider if systemic BP 
>180 mmHg on serial evaluation and/or severe 
ocular manifestations of hypertension. 
• Angiotensin ­converting enzyme (ACE) 
inhibitor—enalapril (0.25–0.5 mg/kg q12h) or 
benazepril (0.25–0.5 mg/kg q12h) and/or 
calcium channel blockers such as amlodipine 
(0.1–0.25 mg/kg q24h); amlodipine is more 
effective in severe hypertension. • Prevention 
of clot formation—consider in proven cardiac 
sources of embolism; antiplatelet therapy with 
low­dose aspirin (0.5 mg/kg PO q24h) or clopidogrel (2–4 mg/kg PO q24h) and low 
molecular weight heparin can be used 
prophylactically; low molecular weight heparin 
80–150 IU/kg SC can be used in suspected or 
confirmed case of hypercoagulable state; 
anti­factor Xa activity should be monitored, 
although this may not be practical.
Mannitol—if suspected elevated ICP unrespon ­
sive to extracranial stabilization measures 
(0.25–2 g/kg IV over 10–20 min up to q4 ­8h).
  FOLLOW-UP
Frequent neurologic evaluations in the first 
48–72 hours to monitor progress.
within 24h for ischemic stroke. • Resolution 
of signs—gradual within 2–10 weeks; some 
dogs/cats may be left with permanent 
neurologic signs due to irreversible brain 
damage. • Dogs with causal medical condition 
significantly more likely to relapse and have 
significant shorter survival time than dogs with 
no identifiable medical condition. • Despite 
having a high likelihood of concurrent disease, 
cat with ischemic stroke have been reported to 
have a favorable short ­term outcome, if neither 
clinical presentation nor concurrent disease 
was severe. • Prognosis for global brain 
ischemia difficult to predict as there are no 
controlled studies.
SYNONYMS
Stroke
• ACE = angiotensin ­converting enzyme. 
• CVA = cerebrovascular accident. • DWI = 
diffusion ­weighted imaging. • FLAIR = 
fluid­attenuated inversion recovery. • ICP = 
intracranial pressure. • MRA = magnetic 
resonance angiography. • TIA = transient 
ischemic attack.
Lowrie M., De Risio L, Dennis R, et al. 
Concurrent medical conditions and 
long­term outcome in dogs with nontrau­
matic intracranial hemorrhage. Vet Radiol 
Ultrasound, 2012, 53:381–388.
Whittaker DE, Drees R, Beltran E. MRI and 
clinical characteristics of suspected 
cerebrovascular accident in nine cats. J 
Feline Med Surg, 2017, 20:674–684.
Author  Laurent GarosiCerebrovascular Accidents  (continued)

Canine and Feline, Seventh Edition  251
C
  BASICS
OVERVIEW
• Most common primary malignant tumor of 
the external ear canal, arising from modified 
apocrine sweat glands (ceruminous glands).
• Often locally invasive, but associated with a 
low metastatic rate.
• Uncommon overall, but the most common 
malignant tumor of the ear canal in both dogs 
and cats, followed by carcinoma of undeter-
mined origin and squamous cell carcinoma.
• Cocker spaniels and German shepherd dogs 
are overrepresented.
• Mean age—dogs, 10 years; cats, 11 years.
• No known sex predisposition.
SIGNS
• Progressive hearing loss.
• Similar to chronic, recurrent otitis externa—  
discharge, odor, pruritus, inflammation.
• Early appearance—pale pink, friable, 
ulcerative, bleeding nodular mass(es) within 
the external ear canal.
• Late appearance—large mass(es) filling the 
canal and invading through canal wall into 
surrounding structures.
• Regional lymph node enlargement.
• Neurologic signs (vestibular signs, Horner’s 
syndrome) may be present secondary to 
middle ear involvement.
• Signs of pain and discomfort; pain upon 
opening the mouth.
Chronic inflammation and ceruminous gland 
hyperplasia/dysplasia appear to play a role in 
tumor development.
  DIAGNOSIS
• Proliferative chronic otitis externa with 
ceruminous gland hyperplasia.
• Inflammatory polyps.
• Other tumors including squamous cell 
carcinoma, basal cell tumor, mast cell tumor, 
papilloma, sebaceous gland tumor, ceruminous 
gland adenoma.
• Ear swab cytology for bacteria and yeast.
• Bacterial culture and sensitivity as needed.
IMAGING
• Skull radiography to assess potential 
involvement of the tympanic bulla, but this is difficult to interpret due to superimposition 
of bones in the skull.
• Thoracic radiography to evaluate for 
• CT or MRI is most useful for loco-regional 
staging and before surgery and radiation 
therapy, providing greater detail than with 
• Cytologic examination of aspirate from 
regional lymph nodes.
• Cytologic examination of fine-needle 
aspirate from mass.
• Biopsy and histopathology.
• Cytology from fine-needle aspirate—round 
to polygonal epithelial cells arranged both 
singly and in large clusters with deep blue to 
lavender-gray cytoplasm and a variable 
quantity of black, intracytoplasmic granular 
material; unable to differentiate adenocarci-
noma from adenoma consistently with 
cytology.
• Histopathologic characteristics—apocrine 
type differentiation from ceruminous glands 
and local invasion into stroma; neoplastic 
cells show moderate to marked nuclear atypia 
with frequent mitotic figures.
  TREATMENT
• Total ear canal ablation and lateral bulla 
osteotomy (TECABO) is the preferred 
surgical approach over lateral ear resection.
• Radiation therapy may be considered for 
either large (palliative intent) or incompletely 
excised masses (curative intent).
• Chemotherapy not evaluated, but 
occasionally considered based on histologic 
information and clinical staging results.
• Multimodal therapy incorporating 
corticosteroids or nonsteroidal anti-inflam-
matory drugs (NSAIDs) and other analgesics.
N/A
  FOLLOW-UP
• Physical examination and thoracic 
radiography at regular intervals following therapy (every 3–4 months) is recommended 
for the first year postoperatively.
• Serial CT or MRI to monitor for local 
tumor regrowth may be recommended.
• Permanent or transient Horner’s syndrome 
secondary to surgery.
• Permanent or transient facial paralysis 
following surgery (more frequent in cats).
• Median survival after lateral ear resection is 
around 10 months for both dogs and cats.
• Median survival after TECABO is >3 years 
in both dogs and cats.
• Median survival after radiation therapy is 
>3 years, but published information is on 
small numbers only.
• Poor prognosis associated with extensive 
tumor involvement (advanced stage), preoper  - 
ative neurologic signs, and conservative 
therapy (e.g., lateral ear canal ablation alone).
• Otitis externa.
• Peripheral vestibular disease, Horner’s 
syndrome.
• Chronic pain.
drug.
• TECABO = total ear canal ablation and 
bulla osteotomy.
Bacon NJ, Gilbert RL, Bostock DE, White 
RA. Total ear canal ablation in the cat: 
indications, morbidity and long-term 
survival. J Small Anim Pract 2003, 
44:430–434.
De Lorenzi D, Bonfanti U, Masserdotti C, 
T ranquillo M. Fine-needle biopsy of 
external ear canal masses in the cat: 
cytologic results and histologic correlations 
in 27 cases. Vet Clin Pathol 2005, 
34:100–105.
Moisan PG, Watson GL. Ceruminous gland 
tumors in dogs and cats: a review of 124 
cases. J Am Anim Hosp Assoc 1996, 
32:448–452.
Théon AP , Barthez PY, Madewell BR, Griffey 
SM. Radiation therapy of ceruminous gland 
carcinomas in dogs and cats. J Am Vet Med 
Assoc 1994, 205:566–569.
Louis-Philippe de Lorimier.Ceruminous Gland Adenocarcinoma, Ear

252  Blackwell’s Five-Minute Veterinary Consult  
CCervical Spondylomyelopathy (Wobbler Syndrome)
  BASICS
• Cervical spondylomyelopathy (CSM) or 
wobbler syndrome is a disease of the cervical 
spine of large- and giant-breed dogs.
• CSM is characterized by compression of the 
spinal cord and/or nerve roots associated with 
neurologic deficits and/or cervical pain.
• Compressive lesion caused by intervertebral 
disc herniation, osseous malformation, 
thickened ligaments, or a combination, in a 
stenotic vertebral canal.
• Disc-associated compression—dogs >3 years; 
intervertebral disc degeneration and subsequent 
protrusion might be secondary to abnormal 
articular facet articulation in Doberman 
pinschers, which predisposes to increased 
rotational strain in the intervertebral discs.
• Vertebral malformation (bony-associated 
compression)—most commonly seen in giant 
breeds of dogs, usually in young adult dogs (<4 
years); the osseous malformation can compress 
the spinal cord dorsoventrally (vertebral arch 
malformation), dorsolaterally (articular process 
malformation/osteoarthritic lesions), or laterally 
(pedicular malformation/osteoarthritic lesions).
• Dynamic spinal cord compression (one that 
changes with movements of the cervical 
spine) is always a component of the patho-
physiology with any type of compression.
• Current evidence does not suggest that 
instability has a primary role in the patho -
genesis of CSM.
Nervous
GENETICS
• Heritable basis proposed for borzoi and 
basset hound.
• Recent evidence suggests that the disease is 
inherited as an autosomal dominant trait 
(with incomplete penetrance) in Doberman 
pinscher.
CSM is probably the most common 
neurologic disorder of the cervical spine of 
large- and giant-breed dogs.
N/A
• Doberman pinscher and Great Dane are the 
most commonly affected breeds, with approxi -
mately 60–70% of cases seen in these breeds.
• Other breeds with a high incidence include 
Rottweiler, German shepherd, Weimaraner, 
Labrador, and Dalmatian.
• CSM can be seen in any breed, including 
small-breed dogs.Mean Age and Range
• Doberman pinschers and other large-breed 
dogs are usually presented >3 years of age, 
with a mean age of 6 years.
• Giant-breed dogs are usually presented 
<3 years of age, although late presentations 
can be seen.
Males overrepresented, primarily in giant-
breed dogs.
SIGNS
The classic clinical presentation is a slowly 
progressive pelvic limb ataxia with less severe 
thoracic limb involvement.
• Chronic, slowly progressive gait dysfunc-
tion is characteristic; acute presentations are 
usually associated with neck pain; occasion-
ally, acute worsening of a dog with chronic 
history is observed.
• Neck pain or cervical hyperesthesia is a 
common historical finding; it occurs in 
approximately 65–70% of Dobermans, and 
40–50% of other breeds.
• Cervical pain is the primary complaint in 
only approximately 5% of patients.
• Gait changes are characterized by proprio-
ceptive ataxia and paresis (weakness); the 
ataxia and paresis are more obvious in the 
pelvic limbs, with lesions in the caudal 
cervical spine (C5–6, C6–7); compressive 
lesions in the mid-cervical spine tend to cause 
ataxia in all four limbs.
• The thoracic limb gait can appear short- 
strided, spastic with a floating appearance, or 
very weak.
• Proprioceptive positioning deficits are 
usually present, but dogs with chronic ataxia 
may not display them; the gait exam (presence 
of ataxia) provides a more sensitive indication 
of myelopathy than proprioceptive position-
ing deficits.
• Dogs can present nonambulatory.
• Supraspinatus muscle atrophy and worn 
toenails can be seen in some cases.
• Extensor muscle tone is commonly 
increased in all four limbs.
• Patellar reflexes are normal or increased; 
flexor reflex may be difficult to elicit in the 
thoracic limbs due to increased extensor tone.
CAUSES
• Nutrition—excess protein, calcium, and 
caloric intake were proposed in Great Danes; 
nutrition does not appear to play a role in the 
development of CSM in large-breed dogs.
• The cause of CSM is likely multifactorial.
• Body conformation—large head and long 
neck have been proposed, but later studies found no correlation between body 
dimensions and incidence of CSM.
• Fast growth rate has been proposed, but not 
confirmed by other studies.
  DIAGNOSIS
• Orthopedic conditions such as hip dysplasia 
and cruciate ligament rupture; differentiated 
by neurologic examination (absence of ataxia).
• Spinal neoplasia, spinal subarachnoid 
diverticulum, spinal synovial cysts, discospon-
dylitis, osteomyelitis, meningomyelitis, trauma; 
differentiated by results of survey radiographs, 
cerebrospinal fluid (CSF), myelography, CT, 
CT myelography, or MRI findings.
N/A
IMAGING
Survey Cervical Radiographs
• Survey radiographs serve as a screening tool 
to rule out bony disorders; although 
intervertebral disc narrowing or vertebral 
tipping can be seen, these findings are not 
specific for CSM since they can be observed 
in clinically normal large-breed dogs.
• Osteoarthritic changes of the articular 
processes can be seen in giant breeds.
Myelography
• Myelography can define the location(s) and 
direction (ventral, dorsal, lateral) of the spinal 
cord compression.
• Stressed views (flexion or extension) may 
cause significant risk of neurologic deterior  - 
ation.
• Linear traction myelography is a safer 
procedure and can distinguish a static from a 
dynamic lesion.
Advanced Imaging
• CT myelography—cross-sectional visualiz- 
ation of the spinal cord compression and 
determination of sites with spinal cord 
atrophy.
• MRI—visualization of the spinal cord 
parenchyma, intervertebral disc, soft tissues, 
and nerve roots; images can be obtained in 
sagittal, transverse, and dorsal planes; spinal 
cord signal changes allow more precise 
identification of the main site of compression 
than CT and myelography; kinematic MRI is 
a novel procedure that allows more precise 
identification of dorsal and ventral lesions, 
primarily when the vertebral column is placed 
in extension.
CSF analysis—usually normal; mild mixed or 
neutrophilic pleocytosis can be seen in dogs with 
acute presentations; elevated protein concentra -
tions can be observed with chronic presentations.

Canine and Feline, Seventh Edition  253
CPATHOLOGIC FINDINGS
• Spinal cord white matter tract demyelina-
tion at the site of spinal cord compression; 
axonal damage can lead to Wallerian degener  - 
ation in the ascending and descending white 
matter tracts.
• Neuronal loss, gliosis, and necrosis can be 
observed in the gray matter.
• Chronic severe focal spinal cord compression 
can lead to focal myelomalacia.
  TREATMENT
• Inpatient if surgical treatment is elected.
• Outpatient if medical management is chosen.
• Nonambulatory dogs—keep patients on 
soft bedding and alternate recumbence side 
every 4 hours to avoid bed sores.
• Bladder catheterization.
• Physical therapy is essential to avoid muscle 
atrophy and ankylosis, and to hasten recovery.
ACTIVITY
• Medically treated dogs should have 
restricted activity for at least 2 months.
• Restriction of activity is also important for 
the first 2 or 3 months postoperatively to allow 
bone fusion and prevent implant displacement.
DIET
Avoid excess of protein, calcium, or caloric 
intake in giant-breed dogs with osseous 
Inform that surgery offers the best chance of 
improvement (approximately 80%), but there 
is a 1–5% risk of significant complications 
associated with cervical surgical procedures.
• Ventral slot—commonly used and 
recommended for single ventral compressions; 
could also be used for two ventral compressions.
• Dorsal laminectomy—primary indication 
for dorsal or dorsolateral compressions; can 
also be used for multiple ventral compres-
sions; hemilaminectomy is an alternative for 
lateralized osseous compressions.
• Distraction/stabilization/fusion techniques 
are recommended primarily for single 
dynamic ventral compressions, but could be 
used for multiple compressions.
• Cervical disc arthroplasty—novel technique 
that appears safe and as effective as the 
traditional procedures; it can be used for 
multiple compressions.
• Recurrence rate is approximately 20% with 
any surgical technique.
• Fenestration provides a very low success rate 
and is not recommended.  MEDICATIONS
• Corticosteroids—prednisone 1 mg/kg q24h 
or 0.5 mg/kg q12h, progressively decreasing 
dosage and frequency; most dogs can have 
prednisone discontinued after 4–8 weeks of 
treatment; dexamethasone 0.1–0.25 mg/kg 
q24h can be used as an alternative to 
prednisone in dogs severely affected; cortico  - 
steroids act by reducing the vasogenic edema 
often present in chronic compressive spinal 
cord lesions.
• Gabapentin—10 mg/kg q8–12h can be 
used for analgesia in cases of more severe 
cervical pain.
N/A
Monitor for signs of gastroenteritis, gastric 
hemorrhage, and cystitis. A proton pump 
inhibitor may be used to minimize the risk of 
gastrointestinal bleeding.
Do not use corticosteroids in combination 
with nonsteroidal anti-inflammatory drugs 
(NSAIDs).
NSAIDs (all kinds) can be used in dogs with 
only cervical hyperesthesia or mild ataxia.
  FOLLOW-UP
Repeat neurologic evaluation as often as 
needed to monitor response to treatment.
• Excessive activity, jumping, and running 
should be avoided.
• Avoid use of neck collars; use a body 
harness instead.
Recurrence of clinical signs can occur in dogs 
treated medically or surgically.
• About 80% of patients improve with surgery.
• Approximately 50% of patients improve 
with medical treatment (restricted activity ± 
corticosteroids) and 25% remain stable.
Dilated cardiomyopathy, hypothyroidism, 
and von Willebrand’s disease are common in 
Doberman pinscher dogs; these diseases can affect diagnostic and treatment options. 
Doberman pinschers suspected of having 
CSM should be routinely evaluated for these 
• Young giant- or large-breed dogs—vertebral 
malformation and compression.
• Older dogs—disc-associated compression.
N/A
N/A
SYNONYMS
• Cervical malformation-malarticulation.
• Cervical spondylopathy.
• Cervical vertebral instability.
SEE ALSO
Intervertebral Disc Disease—Cats.
• CSM = cervical spondylomyelopathy.
• NSAID = nonsteroidal anti-inflammatory drug.
da Costa RC. Cervical spondylomyelopathy 
(wobbler syndrome). Vet Clin North Am 
Small Anim Pract 2010, 40:881–913.
da Costa RC, Parent JM. Outcome of 
medical and surgical treatment in dogs 
with cervical spondylomyelopathy: 104 
cases. J Am Vet Med Assoc 2008, 
233:1284–1290.
De Decker SD, da Costa RC, Volk HA, et al. 
Current insights and controversies in the 
pathogenesis and diagnosis of disc-associated 
cervical spondylomyelopathy in dogs. Vet 
Rec 2012, 171:531–537.
Jeffery ND, McKee WM. Surgery for 
disc-associated wobbler syndrome in the 
dog—an examination of the controversy. 
J Small Anim Pract 2001, 42:574–581.
Martin-Vaquero P , da Costa RC, Drost WT. 
Comparison of noncontrast computed 
tomography and high field magnetic 
resonance imaging in the evaluation of Great 
Danes with cervical spondylomyelopathy. 
Vet Radiol Ultrasound 2014, 55:4.
Provencher M, Habing A, Moore SA, et al. 
Evaluation of osseous-associated cervical 
spondylomyelopathy in dogs using 
kinematic magnetic resonance imaging. Vet 
Radiol Ultrasound 2017, 58:4.
Kinematic magnetic resonance imaging for 
evaluation of disc-associated cervical 
spondylomyelopathy in Doberman 
Pinschers. J Vet Intern Med, 2016 30:4.
Author  Ronaldo Casimiro da Costa
available online(continued)  Cervical Spondylomyelopathy (Wobbler Syndrome)

254  Blackwell’s Five-Minute Veterinary Consult  
CChagas Disease (American Trypanosomiasis)
  BASICS
OVERVIEW
• Caused by hemoflagellate protozoan 
Trypanosoma cruzi .
• T ransmission through contact with infected 
feces of the Reduviid (“kissing”) bug, 
ingestion of bug vector, through blood 
transfusion, or vertical transmission to 
offspring.
• After multiplication at entry site (5 days 
postinfection [PI]), hematogenous spread to 
heart, brain, and other organs.
• Maximal parasitemia at 14 days PI; 
associated with acute myocarditis and (less 
commonly) encephalitis.
• Infection becomes subpatent 30 days PI.
• Dogs then enter long asymptomatic period 
(months to years); subset develop cardio- 
myopathy.
• South and Central America—endemic in 
humans and pets; infected animals are 
sentinels for human risk.
• United States—in southern states with 
infected vectors and reservoir hosts (raccoons, 
opossums, armadillos, mice, rats, squirrels).
• Dogs of any age, breed:
 ∘Acute infection—more severe in dogs 
<2 years old.
 ∘Chronic infection—adults.
 ∘Sporting breeds and outdoor-housed dogs 
more likely to be in contact with vectors or 
reservoir host.
• Cats—more recent evidence of infection 
and organ pathology.
SIGNS
T wo syndromes can be difficult to distin-
guish—acute myocarditis/encephalitis and 
chronic arrhythmias and myocardial 
• Lethargy, weakness.
• Abdominal distension (ascites).
• Syncope, sudden death.
• Ataxia, seizures.
• Tachy- or bradyarrhythmia.
• Heart murmur.
• Congestive heart failure (tachypnea, 
dyspnea, ascites).
• Hepatomegaly.
• Generalized lymphadenopathy (acute).
• Neurologic—weakness, ataxia, seizures 
(acute).
Lives in or travels to endemic area.  DIAGNOSIS
• Cardiomyopathy.
• Congenital heart defect (tricuspid valve 
dysplasia).
• Myocarditis.
• Distemper, other causes of meningo  - 
encephalitis.
Generally normal.
• Cardiac troponin I—elevation indicates 
myocardial damage.
• Serology—presence of T. cruzi  serum 
antibodies (present by 16 days PI) confirms 
infection, but not necessarily clinical disease.
• Tests can cross-react with Leishmania .
• Cytology—trypomastigote (blood form) 
occasionally on blood smear, lymph node 
aspirate, abdominal effusion, or buffy coat 
during period of high parasitemia.
• Cytology—amastigote (intracellular form) 
identified on lymph node aspirate or impression.
• PCR—detect parasite DNA in blood or 
tissue with high specificity; low sensitivity in 
chronic stage if parasite levels low.
IMAGING
• Thoracic radiography—cardiomegaly, 
pulmonary edema, pleural effusion.
• Echocardiography—dilation of heart 
chambers, systolic dysfunction.
ECG
• Supraventricular and ventricular arrhythmias, 
atrioventricular block (any degree), bundle 
branch block.
• Ambulatory ECG (Holter) to document 
• Acute—diffuse granulomatous myocarditis, 
myocardial necrosis, parasitic pseudocysts 
with intracellular amastigotes.
• Chronic—lymphoplasmacytic inflamma-
tion, loss of myocardial fibers, severe 
interstitial fibrosis.
• T. cruzi  amastigotes in heart, lymph nodes, 
liver, spleen, brain.
  TREATMENT
• No currently approved treatment for 
T. cruzi .
• Manage heart failure (see Congestive Heart 
Failure, Left-Sided; Congestive Heart Failure, 
Right-Sided).
• Tachyarrhythmias—anti-arrhythmic drugs.
• Bradyarrhythmias—pacemaker 
implantation.Client Education
• Test housemates/littermates of infected 
dogs.
• Take measures to eliminate the insect 
vector—remove brush, pyrethroid insecticide.
• Alert owner to possible zoonotic risk and 
potential for sudden death.
• Infected female can transfer infection to 
• Cardiology tests (ECG, echocardiography) 
can identify dogs at risk of developing clinical 
signs or sudden death.
Limited therapeutic options for treating 
infection. Variable clinical response to 
Benznidazole; treated dogs still develop 
myocardial damage. Other drug protocols 
under investigation. 
 FOLLOW-UP
• Monitor positive dogs for clinical disease.
• Prognosis unknown for asymptomatic, 
positive dogs.
• Dogs with clinical signs or arrhythmias 
have guarded prognosis.
• Public health concern with limited treat  - 
ment options.
• Risk of human acquiring infection directly 
from infected dog is low, but infected animal 
indicates presence of infected vectors or 
reservoir hosts.
Internet Resources
https://www.cdc.gov/parasites/chagas
Barr SC, Saunders AB, Sykes J. T rypanosomiasis. 
In: Sykes J, ed., Canine and Feline 
Infectious Diseases. Philadelphia, PA: 
Saunders Elsevier, 2013, p. 760.
Meyers AC, Hamer SA, Matthews D, et al. 
Risk factors and select cardiac characteristics 
in dogs naturally infected with Trypanosoma 
cruzi. J Vet Int Med 2019, 33:1695–1706.
Author  Ashley B. Saunders
editors acknowledges the prior contribution 
of Stephen C. Barr.

Canine and Feline, Seventh Edition  255
CChediak-Higashi Syndrome
  BASICS
OVERVIEW
• Autosomal recessive inherited disorder of 
Persian cats characterized by abnormalities in 
cellular morphology and pigment formation.
• Large intracytoplasmic granules in 
circulating leukocytes and melanocytes 
formed by fusion of preexisting granules.
• Storage pool deficiency of adenosine 
diphosphate (ADP), adenosine triphosphate 
(ATP), magnesium, and serotonin results 
from lack of platelet-dense granules.
• Prolonged bleeding from trauma, venipunc-
ture, or minor surgery occurs because of 
impaired platelet aggregation and release 
reaction.
• Normal coagulation times.
• Depressed chemotaxis.
• No change in rates of infection.
• Mildly depressed neutrophil count, but 
within reference interval.
• In humans, it is associated with one of eight 
mutations in the LYST gene.
• Persian cats with dilute smoke-blue coat 
color and yellow-green irises (and white tigers).
• Not reported in dogs.
SIGNS
Prolonged bleeding from trauma, venipuncture, 
or minor surgery.
• Red fundic reflex (lack of choroidal 
pigment).
• Dilute smoke-blue coat color and  yellow- 
green irises.
• Photophobia (blepharospasm and epiphora) 
in bright light.
Genetic disease.
  DIAGNOSIS
Lysosomal storage diseases (e.g., mucopoly-
saccharoidoses), therapy with antiplatelet 
agents (e.g., aspirin, clopidogrel), other 
inherited platelet function defect.
Romanowsky-stained blood smear— 
leukocytes, especially neutrophils, contain 
pink to magenta cytoplasmic inclusions 
approximately 2  μm in diameter.
NoneIMAGING
N/A
Advanced platelet function testing or electron 
microscopy of platelets may provide 
additional evidence for diagnosis.
  TREATMENT
• Provide ascorbic acid (vitamin C) to increase 
cyclic guanosine monophosphate (cGMP) 
concentration and to improve cell and platelet 
function (no controlled studies in cats).
• T ransfusion of platelet-rich plasma or fresh 
whole blood from healthy cats will temporarily 
normalize bleeding time in affected indivi- 
duals.
• Experimentally, bone marrow transplanta-
tion has restored neutrophil and platelet 
function in cats, but is impractical for general 
clinical use.
Ascorbic acid (100 mg PO q8h).
None
  FOLLOW-UP
None
Advise owner of potential for prolonged 
bleeding after trauma, venipuncture, or minor 
surgery.
Prolonged bleeding time.
Normal lifespan, with avoidance of trauma or 
other situations that may predispose to 
bleeding.
• Provide genetic counseling to eliminate 
Chediak-Higashi syndrome from animals 
• Neuter affected and carrier animals or 
advise owner not to breed.ABBREVIATIONS
• ADP = adenosine diphosphate.
• cGMP = cyclic guanosine monophosphate.
August JR. Consultations in Feline Internal 
Medicine, 2nd ed. Philadelphia, PA: 
Saunders, 1994.
Colgan SP , Hull-Thrall MA, Gasper PW, 
et al. Restoration of neutrophil and platelet 
function in feline Chediak-Higashi 
syndrome by bone marrow transplantation. 
Bone Marrow T ransplant 1991, 7:365–374.
Cowles BE, Meyers KM, Wardrop KJ, et al. 
Prolonged bleeding time of Chediak-
Higashi cats corrected by platelet transfu-
sion. Throm Haemost 1992, 67:708–712.
Author  Kenneth S. Latimer

256  Blackwell’s Five-Minute Veterinary Consult  
CChemodectoma
  BASICS
OVERVIEW
• Chemodectomas are tumors arising from 
the chemoreceptor cells (such as in the aortic 
body and the carotid body).
• Other names—aortic body tumors, cardiac 
paraganglioma, APUDoma (amine precursor 
uptake decarboxylase), and glomus body tumor.
• Aortic body tumors more common (80–90%) 
in dogs than carotid body tumors (10–20%).
• Dogs—age 6–15 years.
• Any breeds—but brachycephalic breeds 
predisposed, especially boxers, Boston terriers, 
English bulldogs, and German shepherd dogs.
• Males predisposed for aortic body tumors; 
no sex predilection for carotid body tumors.
SIGNS
• Nonspecific and dependent upon tumor 
size and anatomic localization, and can 
include lethargy, anorexia, weakness, collapse, 
coughing, respiratory distress, exercise 
intolerance, distended abdomen, vomiting, 
sudden death.
• Carotid body tumor—may notice neck 
mass, regurgitation, dyspnea, Horner’s 
syndrome, head tilt, facial nerve paralysis, or 
laryngeal paralysis.
• May be associated with pericardial effusion 
and cardiac tamponade—muffled heart 
sounds, poor pulses, tachycardia, tachypnea, 
weak pulses, slow capillary refill time, ascites.
• May be associated with cranial vena cava 
syndrome (edema of head, neck, and forelimbs).
• May be associated with ascites secondary to 
right heart failure.
• May be associated with pleural effusion—
decreased lung sounds ventrally, cyanosis.
• Cardiac arrhythmias with pulse deficits.
Chronic hypoxia may play a role in the 
development of this disease in brachycephalic 
breeds.
  DIAGNOSIS
• Other masses located at the heart base (i.e., 
hemangiosarcoma, thymoma, ectopic thyroid 
carcinoma, mesothelioma, abscess, and 
granuloma).
• Idiopathic pericardial effusion.
• Pericarditis.
• Valvular insufficiency.
Typically normal, but 36% of patients can 
have nucleated red blood cells without anemia.OTHER LABORATORY TESTS
N/A
IMAGING
• Thoracic radiography—to evaluate for mass 
in the region of the heart base, pericardial 
effusion, metastatic lesions in the lungs.
• Cervical ultrasound, CT, or MRI—to 
evaluate for masses arising in the neck.
• Echocardiography—to image mass and 
aorta/pulmonary arteries/veins.
• Biopsy of mass.
• ECG—if evidence of arrhythmia, may see 
low-amplitude QRS complexes with 
pericardial or pleural effusion, or electrical 
alternans with pericardial effusion.
  TREATMENT
Aortic Body Tumors
• Surgical removal of mass—if possible.
• Subphrenic pericardectomy has been shown 
to prolong survival.
• Symptomatic pericardiocentesis or thoraco  - 
centesis.
• Conformal radiation therapy or stereotactic 
body radiation therapy—discuss with owners 
possible complications including cough, tachy  - 
arrhythmias, and congestive heart failure.
• Palliative thoracoscopic-guided pericardial 
window.
Carotid Body Tumors
Surgical removal if possible—discuss with 
owners possibility of postoperative Horner’s 
syndrome and laryngeal paralysis.
Both
Possible role of chemotherapy (doxorubicin)—
however, definitive studies are lacking.
• The role of chemotherapy in this disease 
has not been published.
• Pharmacologic intervention for cardiac 
  FOLLOW-UP
Serial thoracic radiography or advanced 
imaging for monitoring tumor progression 
and metastasis.
PROGNOSIS
• Carotid body tumors treated with surgery—  
median survival time (MST) 25.5 months.• Aortic body tumors—animals treated with 
pericardectomy MST 730 days vs. animals 
that did not have pericardectomy MST 42 
days. Larger tumors (as determined by tumor 
weight to body weight ratio) more likely 
associated with metastasis.
• Conformal radiation therapy in 1 dog—
survival >42 months.
• Stereotactic body radiation therapy in 6 
dogs—tumor reduction by 30–76% in 4 
dogs, 3 dogs alive 408–751 days post 
radiation therapy, 2 dogs died suddenly at 
150 days and 294 days post radiation therapy, 
and 1 dog died of unrelated causes 1228 days 
post radiation.
SEE ALSO
Pericardial Disease.
• APUD = amine precursor uptake 
decarboxylase.
Kisseberth WC. Neoplasia of the heart. In: 
Withrow SJ, Vail DE, Page RL, eds., Small 
Animal Clinical Oncology, 5th ed. Philadelphia, 
PA: Saunders, 2013, pp. 700–706.

Canine and Feline, Seventh Edition  257
CCheyletiellosis
  BASICS
OVERVIEW
• Contagious parasitic skin disease caused by 
surface-living mites.
• Signs of mild pruritus and scaling resemble 
other more common dermatoses.
• Potential zoonosis.
• System affected—skin/exocrine.
• More severe in young animals.
• Cocker spaniels, poodles, and longhaired 
cats may be inapparent carriers.
SIGNS
• Referred to as “walking dandruff,” because 
of the large mite size and excessive scaling.
• Prevalence varies by geographic region 
owing to mite susceptibility to common 
flea-control insecticides and differences in 
climate.
• Pruritus—usually absent to mild, but can 
be severe: hypersensitivity to mite allergens 
may develop, producing clinical signs similar 
to infestations with Sarcoptes  or Notoedres  
mites.
• Infestation often suspected only after 
lesions in human beings develop (pseudo- 
scabies).
• Scaling— diffuse or plaque like; more 
severe in chronically infested or debilitated 
animals.
• Lesions—dorsal orientation commonly 
noted; head can be affected in cats.
• Underlying skin irritation may be  
minimal.
• Cats may exhibit bilaterally symmetric 
alopecia, bizarre behavior, head shaking, or 
excessive grooming.
• Partial host specificity—dogs: C. yasguri . 
Cats: C. blakei . Rabbits: C. parasitovorax .
• Cheyletiellosis should be considered in 
every animal that shows scaling, with or 
without pruritus.
• Contagion by direct contact or by fomites.
• Common sources of infestation—animal 
shelters, breeders, and grooming facilities.
• Adult female mites may survive in the 
environment up to 10 days.
• Eggs can be found on shed hair.
  DIAGNOSIS
• Keratinization disorders.
• Cutaneous hypersensitivity.• Sarcoptes  and Notoedres  spp. mite infesta-
tion; other fur mites.
• Endocrinopathy.
• Pediculosis.
• Examination of epidermal debris— Cheyle -
tiella mites are large and can be visualized with 
a hand lens or microscope (10× objective); 
scales and hair may be examined under low 
magnification; finding mite eggs is diagnostic.
• Mite numbers may be low—concentration 
of debris for examination increases the 
likelihood of diagnosis; collection of debris: 
flea combing (most effective), skin scraping, 
hair plucking, acetate tape preparation, scale 
collection, and fecal flotation.
• Response to insecticide treatment may be 
required to definitively diagnose suspicious 
cases in which mites cannot be identified.
  TREATMENT
• All animals in the same household must be 
treated.
• Clip long coats to facilitate treatment.
• Weekly baths to remove scale, followed by 
rinses with an insecticide.
• Lime-sulfur rinses—cats, kittens, dogs, and 
puppies.
• Routine flea sprays—not always effective: 
treat all animals in the home before introduc-
ing a new pet.
• Environmental treatment with frequent 
cleanings and insecticide sprays—reduces 
possibility of reinfestation.
• Continue treatment for at least 6–8 weeks 
to prevent reinfestation from shed eggs.
• Combs, brushes, and grooming tools—  
discard or thoroughly disinfect before reuse.
• Amitraz rinses—dogs only; 2-week intervals 
for 4 applications.
• Fipronil—2-week intervals for 1–4 applications.
• Ivermectin—300  μg/kg PO/SC 3 times at 
2-week intervals; dogs and cats >3 months 
old; pour-on forms have shown efficacy in 
cats (500  μg/kg 2 times at 2-week intervals; 
non-FDA-approved usage; see Contraindications/
Possible Interactions).
• Selamectin—apply every 2–4 weeks for 
3 applications (non-FDA-approved usage).
• Imidacloprid/moxidectin—apply every 
2 weeks for 3 applications (non-FDA-
approved usage); imidacloprid alone: not 
effective.• Milbemycin oxime—2 mg/kg PO once 
weekly for 4 weeks.
• Moxidectin—subcutaneous injection every 
2 weeks for 3 treatments (non-FDA-approved 
usage: dogs).
• Doramectin—subcutaneous injection every 
week for three treatments (non-FDA-approved 
Prevent ingestion/avoid use of avermectins in 
sensitive dogs ( MDR1 /ABCB1  gene muta-
tion, collie, sheltie, Australian shepherd, Old 
English sheepdog)—selamectin may be used 
in these dog breeds.
  FOLLOW-UP
• T reatment failure requires a thorough 
reevaluation for other causes of pruritus and 
scaling.
• Reinfestation may indicate contact with an 
asymptomatic carrier or the presence of an 
unidentified source of mites
Pruritic papular rash may develop in human 
beings.
Hnilica KA, Paterson A. Small Animal 
Dermatology: A Color Atlas and 
Therapeutic Guide, 4th ed. St. Louis, MO: 
Elsevier, 2017.
Saari S, Näreaho A, Nikander S. Canine 
Parasites and Parasitic Diseases. London: 
Academic Press, 2019.
Taylor MA, Coop RL, Wall RL. Veterinary 
Parasitology. Ames, IA: Wiley-Blackwell, 2016.
Author  Guillermina Manigot
Resnick

258  Blackwell’s Five-Minute Veterinary Consult  
CChlamydiosis—Cats
  BASICS
A chronic respiratory infection of cats caused 
by an intracellular bacterium, characterized 
by mild to severe conjunctivitis, mild upper 
respiratory signs, and mild pneumonitis.
• Chlamydophila felis  (previously Chlamydia 
psittaci var. felis )—a Gram-negative, obligate 
intracellular bacterium spread through close 
contact, aerosolization, or genital contact 
during parturition.
• Replicates on the mucosa of the upper and 
lower respiratory epithelium; produces a 
persistent commensal flora that causes local 
irritation, resulting in mild upper and lower 
respiratory signs and conjunctivitis; can also 
colonize the mucosa of the gastrointestinal 
and reproductive tracts.
• Incubation period—7–10 days (longer than 
that of other common feline respiratory 
pathogens).
• Gastrointestinal—cat: infection without 
clinical disease; other species: may have 
clinical gastroenteritis.
• Ophthalmic—acute or chronic conjunctivi-
tis, unilateral often progresses to bilateral.
• Reproductive—infection without clinical 
disease.
• Respiratory—mild rhinitis, bronchitis, and 
bronchiolitis.
GENETICS
None
• Incidence of clinical disease—sporadic; 
outbreaks of respiratory disease may occur, 
especially in multicat facilities.
• Prevalence of C. felis  in the feline popula-
tion: ~5–10% chronically infected.
Worldwide
Species
• Cat
• Human
None
Usually cats >8 weeks and <1 year of age; any 
age of cat possible.
None
SIGNS
• Commonly associated with feline 
conjunctivitis.• Infection often subclinical.
• Clinical disease—commonly coinfection 
with other organisms, such as feline herpesvirus 
(FHV) and feline coronavirus (FCV).
• Primarily signs of ocular discharge, 
blepharospasm.
• Mild upper respiratory infection, with 
possible sneezing and oculonasal discharge.
• Varying degrees of anorexia, lethargy.
• Lameness possible (uncommon).
• Conjunctivitis—unilateral or bilateral 
chemosis, blepharospasm, conjunctival and 
third eyelid hyperemia; serous to mucopurulent 
discharge without keratitis.
• Mild nasal discharge.
• Fever.
• Dyspnea and cough extremely unlikely; 
rales with pneumonitis.
• Concurrent infections with other respira-
tory pathogens (FHV, FCV, Bordetella 
bronchiseptica , Mycoplasma felis ).
• Lack of vaccination.
• Multicat facilities, especially adoption 
shelters and breeding catteries.
• Stress.
• Presence of asymptomatic shedders.
 DIAGNOSIS
• Feline herpesvirus infection—short incuba -
tion period (4–5 days), rapid bilateral conjuncti -
vitis, severe sneezing, and ulcerative keratitis.
• Feline calicivirus infection—short 
incubation period (3–5 days), ulcerative 
stomatitis, and potentially pneumonia.
• Mycoplasma felis .
Leukocytosis possible.
IMAGING
Thoracic radiographs—consolidation of lung 
tissue with pneumonia.
• PCR—preferred; best sensitivity; submit 
conjunctival swab in a sterile red top tube 
with a small amount of sterile saline.
• Culture—obtain conjunctival swab with 
vigorous exfoliation and submit on ice within 
24 hours in special transport media such as 
2-sucrose-phosphate (2-SP).
• Conjunctival cytology—characteristic 
intracytoplasmic basophilic inclusions may be 
seen with Giemsa staining early in disease.
• Serum antibody titers—limited diagnostic 
value.
• ELISA kits—variable sensitivity and 
specificity.PATHOLOGIC FINDINGS
• Gross—chronic conjunctivitis with 
mucopurulent ocular discharge; minor 
rhinitis with nasal discharge; sometimes lung 
changes indicative of pneumonitis.
• Histopathologic (conjunctiva)—an early 
intense infiltration of neutrophils; inflamma-
tory response changes to lymphocytes and 
plasma cells; inclusions detected with special 
stains (inclusions invisible with routine H&E 
stains).
 TREATMENT
Generally outpatient.
• Clean eyes and nose as necessary with warm 
water or saline.
• Provide access to steam, such as in a bath  - 
room, to clear secretions.
• Provide palatable, soft foods; warming food 
can improve cat’s olfaction.
• Generally does not require other supportive 
therapy (e.g., fluids), unless complicated by 
concurrent infections.
ACTIVITY
• Quarantine affected cats from contact with 
other cats.
• Do not allow affected cats to go outside.
DIET
• No restrictions.
• Special diets—to entice anorectic cats to 
resume eating.
Inform clients of the causative organism, the 
anticipated chronic course of disease, and the 
opportunity to vaccinate other cats before 
exposure.
 MEDICATIONS
• Ophthalmic ointments—usually beneficial; 
oxytetracycline 3-4 times daily for 3 weeks; 
preparations with polymyxin may be 
irritating for cats; alternatively erythromycin 
or fluoroquinolone ointment; resistant to 
bacitracin, neomycin, gentamicin.
• Systemic antibiotics—tetracyclines are 
antibiotic of choice; doxycycline (10 mg/kg 
PO q24h or 5 mg/kg PO q12h for 4 weeks to 
prevent recrudescence); amoxicillin-clavulanate 
(20–25 mg/kg PO q12h) as alternative for 
young kittens.
Tetracyclines—risk for esophagitis; may affect 
growing teeth of young kittens.

Canine and Feline, Seventh Edition  259
C(continued)  Chlamydiosis—Cats
Colonies/shelters/breeding catteries—all cats 
may have to be treated; treatment should be 
continued for 4 weeks.
None
None
 FOLLOW-UP
Monitor for improved health as treatment 
proceeds.
Vaccines
• Both inactivated and modified live vaccines 
available.
• Vaccines do not prevent infection; rather, 
they reduce severity and duration of clinical 
disease.
• American Association of Feline 
Practitioners—noncore vaccine; for at-risk 
cats, give a single vaccination at initial visit as 
early as 9 weeks of age, repeat in 3–4 weeks; 
revaccinate annually where C. felis  is endemic.
• Adverse vaccine reactions—mild clinical 
disease with modified live vaccines in small 
percentage of vaccinated cats.
Environmental Management
• Quarantine affected cats by >4 ft perimeter.
• Practice appropriate hygiene and beware of 
fomites.
• C. felis  readily inactivated with common 
disinfectants.
• If kittens are affected <2 weeks of age, 
eyelids may need to be surgically opened to 
allow for drainage of purulent material 
(ophthalmia neonatorum).• If entire course of antibiotics are not 
completed, persistently infected cats can 
become asymptomatic shedders.
• Coinfections increase morbidity.
PROGNOSIS
• Without treatment, tends to be chronic, 
lasting for several weeks or months.
• Prognosis good with appropriate antibiotic 
therapy.
• Improvement in 1–2 days with therapy; 28 
days of treatment needed to clear organism.
• Look for coinfections if not improving as 
expected.
 MISCELLANEOUS
Affected cats may be concurrently infected 
with FHV or FCV, especially in multicat and 
breeding facilities.
Primarily a disease of young cats.
C. felis  can infect humans, especially immuno  - 
compromised individuals; limited number of 
reports of mild conjunctivitis in humans 
transmitted from infected cats.
• Endemic breeding catteries—treat all cats 
with doxycycline for at least 4 weeks; then 
vaccinate.
• Role of C. felis  as a pathogen during 
pregnancy—unclear; can colonize the 
reproductive mucosa; severe ophthalmia 
neonatorum can occur in neonatal kittens 
infected at or shortly after birth.
SYNONYMS
Feline pneumonitis.SEE ALSO
• Feline Calicivirus Infection.
• Feline Herpesvirus Infection.
• Feline (Upper) Respiratory Infections.
• Ophthalmia Neonatorum.
• 2-SP = 2-sucrose-phosphate.
• FCV = feline calicivirus.
• FHV = feline herpesvirus.
http://www.abcdcatsvets.org/
chlamydia-chlamydophila-felis
Hartmann AD, Hawley J, Werckenthin C, 
et al. Detection of bacterial and viral 
organisms from the conjunctiva of cats with 
conjunctivitis and upper respiratory tract 
disease. J Feline Med Surg 2010; 
12:775–782.
Scherk MA, Ford RB, Gaskell RM, et al. 
2013 AAFP Feline Vaccination Advisory 
Panel Report. J Feline Med Surg 2013; 
15:785–808.
Sykes JE. Pediatric feline upper respiratory 
disease. Vet Clin North Am Small Anim 
Pract 2014; 44:331–342.
Sykes JE, Greene CE. Chlamydial infections. 
In: Greene CE, ed., Infectious Diseases of 
the Dog and Cat, 4th ed. St. Louis, MO: 
Saunders Elsevier, 2012, pp. 270–276.
Author  Sara E. Gonzalez
Fred W. Scott.
 Client Education Handout  

260  Blackwell’s Five-Minute Veterinary Consult  
CChocolate Toxicosis
 BASICS
• Chocolate, derived from the seed of the 
Theobroma cacao  plant, contains the naturally 
occurring methylxanthine alkaloids theobromine 
and caffeine. • Excessive intake can lead to 
dose-dependent gastroenteric, cardiac, and 
neurologic toxicosis. • Theobromine is the largest 
fraction of methylxanthines in chocolate 
products; lower concentration of caffeine is 
present (Table 1). Other sources of methylxan -
thines include coffee, tea, diet pills, over-the-
counter (OTC) stimulants, and herbal medications.
• Variably absorbed orally (caffeine <1 hour; 
theobromine 10 hours), metabolized by liver, 
undergo enterohepatic recirculation; metabo -
lites primarily excreted via urine and may be 
reabsorbed from urinary bladder. • Estimated 
theobromine and caffeine half-lives in dogs 
17.5 hours and 4.5 hours, respectively.  
• Methylxanthines inhibit phosphodiesterase 
to increase intracellular cyclic adenosine 
monophosphate (cAMP), stimulate catechola -
mine release, and increase intracellular calcium, 
which results in vasoconstriction, increased 
myocardial and skeletal muscle contractility, 
and CNS stimulation. • Toxic dosages:  
◦ Theobromine—LD50 (dog) 250–500 mg/kg; 
LD50 (cat) 200 mg/kg. Mild signs (agitation, 
vomiting, diarrhea): 20 mg theobromine/kg. 
Moderate signs (tachycardia): 40–50 mg 
theobromine/kg. Severe signs (seizures): 60 mg 
theobromine/kg. ◦ Caffeine—LD50 (dog) 140 
mg/kg; LD50 (cat) 80–150 mg/kg. Clinical 
signs: >15 mg caffeine/kg. Moderate signs: >25 
mg caffeine/kg. Cardiotoxic signs: >50 mg 
caffeine/kg. • Several aids to assess canine risk 
from chocolate can be found online—see 
Internet Resources.
• Cardiovascular—tachycardia, hypertension, 
ventricular premature contractions (VPCs), 
other tachyarrhythmias, bradycardia (rare).  
regurgitation. • Metabolic—hypokalemia, 
hyperthermia, dehydration. • Nervous— 
agitation, tremors, seizures, ataxia, muscle 
rigidity, hyperreflexia. • Renal/urologic—
polyuria, polydipsia. • Respiratory—panting, 
tachypnea, cyanosis, respiratory failure.
• Dogs—among 10 most common poisonings 
reported by small animal practices and animal 
poison control centers. • More common at 
holidays when chocolate products readily 
Indoor dogs at risk owing to closer proximity 
to chocolate products.SIGNALMENT
Species
• Dogs most frequently poisoned based on 
proximity to methylxanthine products and 
propensity for dietary indiscretion leading to 
excessive ingestion. • Cats rarely affected.
• Small dogs may be at higher risk due to 
smaller body weight relative to amount of 
chocolate consumed. • Breeds prone to 
dietary indiscretion, such as Labrador retrievers.
SIGNS
• History of ingestion. • Evidence of chewed 
packaging. • Vomiting and diarrhea—vomit 
often contains evidence of chocolate and may 
be first sign noted. • Early restlessness and 
hyperactivity. • Polydipsia.
• Physical exam may be normal after recent 
ingestion (<1–2 hours). • Vomiting. • Diarrhea. 
• Restlessness and hyperactivity. • Panting.  
• Polyuria/polydipsia. • Dehydration.  
• Tachycardia. • Cardiac arrhythmias such 
as VPCs. • Hypertension. • Hyperthermia.  
• T remors. • Hyperreflexia and muscle 
rigidity. • Seizures. • Advanced signs with 
severe toxicosis—cardiac failure, weakness, 
cyanosis, coma, and death. • Death—12–48 
hours after ingestion.
CAUSES
Excessive ingestion of chocolate and other 
methylxanthine products.
• Access to chocolate, which is palatable and 
attractive to dogs, often readily available, and 
unprotected in homes and kitchens. • Dogs 
with preexisting heart disease may be more 
sensitive to cardiac effects.
 DIAGNOSIS
• Convulsant or excitatory alkaloids—  
strychnine, amphetamine, nicotine,  
4-aminopyridine. • Convulsant pesticides 
such as pyrethroids, organochlorines, 
bromethalin, zinc phosphide, metaldehyde.  
• T remorgenic mycotoxins. • Acute psycho-
genic drugs—LSD, cocaine. • Medications 
such as phenylpropanolamine, pseudoephed-
rine, tricyclic and selective serotonin reuptake 
inhibitor antidepressants. • Cardioactive 
glycosides— Digitalis  spp., Nerium oleander .  
• Primary GI, cardiac, or neurologic disease.
• Hyperglycemia or hypoglycemia.  
• Hypokalemia, especially with caffeine 
overdose. • Urine may be dilute due to 
polydipsia.OTHER LABORATORY TESTS
• Methylxanthine assay—rarely necessary as 
history and clinical signs usually sufficient for 
diagnosis; can be performed on stomach 
contents, plasma, serum, urine, or liver.
• ECG monitoring—sinus tachycardia, 
VPCs, and ventricular tachyarrhythmias.  
• Presence of chocolate in GI tract. • Nonspecific 
gastroenteritis. • No distinctive microscopic lesions.
  TREATMENT
• Emesis in stable patients considered low risk for 
aspiration; chocolate is slowly absorbed from a 
dog’s stomach, so emesis may be rewarding up to 
6–8 hours after ingestion. • Gastric lavage with 
cuffed tube in symptomatic patients with 
large-volume ingestions once stabilized.  
• Activated charcoal may not be necessary with 
lower-dose exposures or in cases where most of the 
chocolate was recovered by induction of vomiting 
or gastric lavage; monitor electrolytes for hyperna -
tremia if giving multiple doses of activated 
charcoal. • IV fluid therapy to correct dehydra -
tion, promote urinary excretion of methylxan -
thines, and avoid hypernatremia; SC fluids may 
suffice with lower-dose exposures; potassium may 
be supplemented in fluids, if needed. • Control 
hyperthermia. • Urine voiding every 4 hours or 
urinary catheterization may reduce urinary 
bladder resorption. • GI support as needed  
(see Medications). • Control hyperactivity and 
agitation, tremors, seizures (see Medications).  
• T reat tachycardia with beta blockers, if sedation 
not effective; treat arrhythmias with anti-arrhyth -
mic drugs as appropriate (see Medications).
Fluid therapy used to correct electrolyte 
disturbances and dehydration and to enhance 
excretion of methylxanthines.
ACTIVITY
Avoid stress and limit activity until recovered.
DIET
• No food until vomiting is controlled.  
• Convalescence—bland, low-fat diet to aid 
recovery from gastroenteritis and/or pancreatitis.
Warn owners about toxicologic hazards of 
chocolate, and advise keeping chocolate out 
of reach of dogs.
• Induce emesis— only if patient is stable 
with low risk of aspiration ; apomorphine

Canine and Feline, Seventh Edition  261
C(continued)  Chocolate Toxicosis 
(0.02–0.04 mg/kg IV); hydrogen peroxide 3% 
(1–2 mL/kg PO); do not exceed 50 mL in dogs. 
• Activated charcoal 1–2 g/kg PO with cathartic 
× 1 dose. With large ingestions, repeat activated 
charcoal (no cathartic) q8 up to 24h to prevent 
enterohepatic recirculation. • Hyperactivity—  
acepromazine (0.02–0.04 mg/kg IV/IM/SC) or 
butorphanol (0.2–0.5 mg/kg IM/IV), with 
doses repeated/titrated to effect. • Seizures—
diazepam (0.5–1 mg/kg IV) or phenobarbital 
(2–6 mg/kg IV) as needed to effect. • T remors—  
diazepam (0.5–1 mg/kg IV) or methocarbamol 
(50–220 mg/kg IV slowly, up to daily dose of 
330 mg/kg). • Vomiting—maropitant (1 mg/kg 
SC or IV) q24h as needed. • Persistent ventricular 
tachycardia—metoprolol (0.04–0.06 mg/kg IV), 
esmolol (initial loading dose 0.25–0.5 mg/kg IV 
slowly over 1–2 min, followed by CRI at 
10–200  μg/kg/min) or propranolol (0.02–
0.06 mg/kg IV); metoprolol or esmolol preferred 
but may be difficult to obtain. • Ventricular 
arrhythmias (dogs)—  lidocaine (2–4 mg/kg IV 
followed by 25–100  μg/kg/min IV CRI); 
lidocaine not recommended in cats. • In rare 
instance of bradycardia—atropine 0.02–0.04 mg/
kg IV/IM/SC; rule out reflex bradycardia from 
hypertension before use.
• Do not use epinephrine concurrent with 
lidocaine. • Avoid erythromycin and cortico  - 
steroids, which may reduce excretion of 
methylxanthines. • Do not use lidocaine in 
cats due to risk of seizures.
Keep patient under observation until 
recovered and treatment no longer needed.  FOLLOW-UP
Monitor heart rate, blood pressure, ECG, 
mentation, and temperature closely while 
hospitalized.
chocolate and advise keeping chocolate out of 
reach of dogs.
• Aspiration can occur rarely secondary to 
vomiting. • Pancreatitis can occur in some 
patients that consume chocolate.
• Expected course—12–36 hours, up to 72 
hours in severe cases, depending on dosage and 
effectiveness of decontamination and treatment. 
• Successfully treated patients—usually recover 
completely. • Prognosis—good if prompt oral 
decontamination occurs, but guarded with 
advanced signs of seizures and arrhythmias.
Methylxanthines cross the placenta and are 
excreted in milk.
SEE ALSO
• Antidepressant Toxicosis—SSRIs and SNRIs.
• Metaldehyde Toxicosis.
• Poisoning (Intoxication) Therapy.ABBREVIATIONS
• cAMP = cyclic adenosine monophosphate.
• OTC = over the counter.
• https://www.aspca.org/pet-care/animal-
poison-control/apcc-mobile-app
• https://www.merckvetmanual.com/en-ca/
toxicology/food-hazards/chocolate
Dolder LK. Methylxanthines. In: Peterson M, 
Talcott P , eds., Small Animal Toxicology, 
3rd ed. St. Louis, MO: Elsevier Saunders, 
2013, pp. 647–652.
Hoffberg JE. Chocolate and caffeine. In: 
Hovda LR, Brutlag AG, Osweiler G, 
Peterson K. The 5 Minute Veterinary 
Clinical Companion Consult: Small Animal 
Toxicology, 2nd ed. Ames, IA: Wiley-
Blackwell, 2016, pp. 479–484.
Luiz JA, Heseltine J. Five common toxins 
ingested by dogs and cats. Compend 
Contin Educ Pract Vet 2008, 30:578–587.
Author  Charlotte Flint
Client Education Handout  
available onlineComparative concentrations of caffeine and theobromine
Caffeine Source Amount (mg/g) Amount (mg/oz) *
Coffee beans 10–20 284–570
Drip coffee 90–100 mg/6 oz cup 15–20
Cola drinks 30–71 mg/12 oz can 2.5–6
Baking chocolate (unsweetened) 0.8 23
Dark chocolate 0.43–0.8 12–23
Milk chocolate 0.2 6
Cocoa powder (unsweetened) 2.3 70
Guarana 30–50 850–1,400
Caffeine stimulant tablets 50–200 mg/tablet —————
OTC migraine pain control 65 mg/tablet —————
Theobromine Source Amount (mg/g) Amount (mg/oz)
Cacao beans 10–50 300–1500
Baking chocolate (unsweetened) 13–16 370–454
Milk chocolate 1.5–2 42–57
Cacao bean hulls 5–9 142–256
Cacao bean mulch 2–30 57–852
Cocoa powder (unsweetened) 14–29 398–832
* To convert mg/g to mg/oz, multiply by 28.4.Table 1

262  Blackwell’s Five-Minute Veterinary Consult  
CCholangitis/Cholangiohepatitis Syndrome
  BASICS
• Cholangitis—bile duct inflammation.
• Cholangiohepatitis—inflammation of bile 
ducts and adjacent liver parenchyma.
• Cholangitis/cholangiohepatitis syndrome 
(CCHS)—more common in cats; histologically 
classified as suppurative (predominant 
neutrophilic inflammation, S-CCHS); 
nonsuppurative (lymphocytic, plasmacytic, 
NS-CCHS); lymphoproliferative (may transition 
to lymphosarcoma); or granulomatous.
• Antecedent or coexisting conditions—
inflammation or obstruction involving 
extrahepatic bile duct (EHBDO) or 
pancreatic duct (cat), pancreatitis or 
inflammatory bowel disease (IBD; dog, cat); 
chronic interstitial nephritis (CIN; cat).
• Bacterial infection may be primary or 
secondary.
• Acute or chronic cholangitis—associates 
with biliary epithelial hyperplasia and 
ductular reaction.
• Chronic inflammation—may cause bile duct 
dystrophic mineralization or cholelithiasis.
• S-CCHS—usually positive bacterial culture 
or bacteria observed cytologically (tissue or 
bile); rarely observed in liver tissue, may 
observe in gallbladder (GB).
• NS-CCHS—immune-mediated and 
self-perpetuating, may evolve from S-CCHS.
• Sclerosing or destructive cholangitis—bile 
duct involution/destruction, may be immune 
mediated or infectious; leads to loss of small 
and medium-sized bile ducts (ductopenia) 
with “sclerosing” circumferential fibrosis; 
ductopenia is severe lesion.
• Pyogranulomatous CCHS—infectious or 
immune mechanisms (dog or cat).
• Lymphoproliferative disease—speculated 
transition stage of inflammation to 
• Hepatobiliary—liver and biliary system.
• Gastrointestinal (GI)—pancreas and 
intestines.
NS-CCHS—most common chronic liver 
disorder in cats.
Species
Cat (common), dog (uncommon).
Possibly Himalayan, Persian, Siamese cats.
• S-CCHS—range: 0.4–16 years; mostly 
young to middle-aged cats.• NS-CCHS—range: 2–17 years; mostly 
middle-aged cats.
• S-CCHS—male cats may be predisposed.
• NS-CCHS—no sex prevalence.
SIGNS
• S-CCHS—most severe clinical illness, acute 
onset (often <5 days); abdominal pain, 
pyrexia; associated with EHBDO and 
cholelithiasis.
• NS-CCHS—ill >3 weeks (months to 
years).
Feline CCHS—cyclic illness with chronic 
vague signs: lethargy, vomiting, anorexia, 
weight loss; ductopenic cats demonstrate 
polyphagia, acholic stools, variable 
steatorrhea, reduced uptake of fat-soluble 
substances.
• S-CCHS—fever; painful abdomen; ± 
jaundice; dehydration; shock.
• NS-CCHS—few physical abnormalities 
other than variable hepatomegaly; thickened 
intestines with IBD; variable jaundice; rare 
abdominal effusion.
• Ductopenia (cats)—unkempt coat, cyclic 
lateral thoracoabdominal alopecia; jaundiced; 
acholic feces (may be cyclic).
CAUSES
Suppurative CCHS
• Infections acquired as result of ductal plate 
malformations (DPM), all phenotypes but 
most commonly choledochal cyst and caroli 
phenotypes.
• Bacterial infection—more common in 
cats: E coli and Enterococcus  most common, 
but numerous bacteria (e.g., Enterobacter , 
β-hemolytic Streptococcus , Klebsiella , 
Actinomyces , Clostridia , Bacteroides ); rare 
toxoplasmosis; dogs: usually enteric 
opportunists; rare Campylobacter , 
Salmonella , Leptospirosis , others.
• Aerobic infections commonest, poly -
microbial infections in ~30%.
• May represent sequela to intermittent 
mechanical bile flow stasis or EHBDO; DPM 
with cholelithiasis most common associated 
disorder.
Nonsuppurative CCHS
Concurrent disorders—cholecystitis, 
cholelithiasis, pancreatitis, EHBDO, IBD 
(dogs, cats); CIN (cats).
• S-CCHS—EHBDO; cholelithiasis; DPM; 
other causes of cholestasis; infections 
elsewhere (dental, splenic abscess, pyelo  - 
nephritis).
• Feline NS-CCHS—IBD, pancreatitis, 
EHBDO, cholelithiasis, CIN; may evolve 
from chronic intermittent S-CCHS.  DIAGNOSIS
DIFFERENTIAL DIAGNOSES
• Feline hepatic lipidosis (FHL)—may 
coexist; similar enzyme patterns with jaundice 
but low γ-glutamyl transferase (GGT) unless 
concurrent biliary or pancreatic inflamm- 
ation.
• EHBDO and obstructive cholelithiasis; 
variable jaundice, increased alkaline 
phosphatase (ALP), GGT, transaminase 
activities; increased cholesterol.
• Pancreatitis—may reflect cholelithiasis-
initiated CCHS in cats; lipemia, high 
cholesterol, hyperbilirubinemia; inconsistent 
high feline pancreatic lipase activity (fPLI); 
high fPLI implicates pancreatic inflammation 
but also may reflect IBD, pancreatic duct 
inflammation/obstruction from cholelithiasis; 
ultrasound may differentiate.
• Lymphoproliferative disease and lymphoma—  
may involve any enteric segment, mesenteric/
thoracic lymphadenopathy; shares clinical 
features with CCHS; hepatic infiltrates may 
require immunohistochemical characterization 
and clone evaluation to differentiate 
lymphoproliferative or lymphoma from 
NS-CCHS.
• Jaundice of septicemia—hyperbilirubi -
nemia dominates clinical biochemical 
features, usually disproportionate to 
magnitude of liver enzyme activity unless 
concurrent CCHS.
• DPM occur in dogs, cats, esp. longhaired 
cats (Persian and Himalayan)—normal or 
modestly increased liver enzymes (see 
Ductal Plate Malformations); variable 
mild to moderate suppurative or 
nonsuppurative portal aggregates, 
cholangitis, or CCHS.
CBC
• Poikilocytes; nonregenerative anemia; 
anemia of chronic disease; Heinz body 
• S-CCHS—variable neutrophilic leukocytosis, 
left shift, toxic neutrophils; NS-CCHS—may 
be normal; lymphoproliferative disorder or 
lymphoma may have lymphocytosis ± abnormal 
cell morphology.
Serum Biochemistry
• Consistent findings—high alanine 
aminotransferase (ALT), aspartate aminotrans -
ferase (AST), ALP , variable GGT.
• Variable findings—high total serum bile 
acids, bilirubin, cholesterol: depends on 
severity and extent of cholestasis, coexistent 
illness, liver dysfunction, cholelithiasis, 
DPM-associated hepatic fibrosis.

Canine and Feline, Seventh Edition  263
C
• Species-specific PLI—may be high with 
pancreatitis, enteritis, or cholelith occlusion 
of bile duct ampulla in cats.
• Vitamin B12—low values indicate small 
bowel malabsorption, exocrine pancreatic 
disease, chronic oral antimicrobials (dysbiosis).
• Coagulation tests—variable results; 
prothrombin time most sensitive for vitamin 
K1–induced coagulopathy.
• T4—rules out hyperthyroidism as cause of 
increased liver enzyme activity in cats.
IMAGING
• Thoracic radiography—sternal lympha -
denopathy may reflect abdominal 
inflammation or lymphoma, general lympha  - 
denopathy suggests lymphoma.
• Abdominal radiography—normal to large 
liver in NS-CCHS; mineralized choleliths or 
biliary structures in S-CCHS or NS-CCHS.
• Abdominal US—normal to large liver; thick 
extrahepatic bile duct or GB wall if choledochitis 
or cholecystitis; echogenic intraluminal debris; 
choleliths; focal parenchymal lesions (abscess, 
infiltrates: inflammation, neoplasia); lympha -
denopathy suggests pancreatic, liver, intestinal 
inflammation or neoplasia; hepatic parenchymal 
hyperechogenicity (concurrent FHL, fibrosis); 
hypoechogenicity (inflammation); cysts (DPM, 
cystadenoma). Note: no US lesions apparent in 
some animals with CCHS.
Fine-Needle Aspiration Cytology
• Hepatic aspiration—for culture and 
diagnosis of FHL; cytology may reveal 
bacteria not visualized by light microscopy of 
biopsy sections. Note: cytology is diagnostic 
for FHL but unreliable for diagnosis of 
NS-CCHS; hepatocyte vacuolation common 
in ill cats, may implicate FHL as primary 
process when consequence of primary hepatic 
disease.
• Cholecystocentesis—may disclose 
suppuration, bacteria, trematode eggs, or 
Percutaneous Biopsy
• US-guided core-needle biopsy—small 
sample size may misdiagnose CCHS; need 
min 15 portal triads for accuracy; if 18-G 
core needle used, collect min 4 samples.
• Inaccuracy with needle biopsy in feline 
CCHS reflects biopsy of single liver lobe in 
syndrome with differential lobe involvement 
or small sample size.
• Postbiopsy complications—esp. cats: 
collapse due to vasovagal response; biliary 
trauma; cats and tiny dogs: unintentional 
sampling of nonhepatic tissues.
Laparoscopy
• Permits direct visualization of GB, common 
bile duct (CBD), porta hepatis, pancreas, 
perihepatic and peripancreatic lymph nodes; allows biopsy of multiple liver lobes, pancreas, 
aspiration collection of bile.
• In EHBDO—not recommended, see 
Laparotomy.
Laparotomy
• Esp. if suspected EHBDO or choleliths in 
CBD or GB.
• Permits inspection and flushing of 
extrahepatic biliary conduits; biliary 
decompression and biliary enteric anastomosis.
• May be preferable approach in cats with 
CCHS as allows biopsy of liver, biliary 
structures, pancreas, intestines, lymph nodes, 
bile collection.
Tissue Sampling
If NS-CCHS suspected, also biopsy bowel, 
pancreas, and suspicious lymph nodes.
Bile and Tissue Cultures
• Aerobic and anaerobic bacterial cultures—
of liver, bile, any choleliths (crushed); bile 
sample should include particulate debris 
(empty GB to collect mucin-laden bile: site of 
bacterial biofilm).
• If cholecystectomy done—scrape portion of 
GB wall and cut section of GB wall for culture.
• Put bile, GB wall, crushed cholelith, liver in 
same culture transport medium.
Molecular Genetics
Genetic test for feline polycystic disease may 
be appropriate if DPM diagnosis, especially if 
breeding animal.
• S-CCHS—normal or swollen liver, sharp or 
blunt edges, focal discolorations; may note 
erythematous, necrotic, or thick-walled GB; 
peripancreatic steatonecrosis or fat saponi -
fication (pancreatitis); perihepatic and 
peripancreatic lymphadenopathy; EHBDO: 
may observe choleliths or cystic lesions (DPM) 
or neoplastic mass lesions.
• NS-CCHS—variable liver size, normal to 
firm texture; sharp or blunt margins; variable 
surface irregularity; choleliths or cystic lesions 
(DPM phenotypes).
• If concurrent FHL—pale yellow friable 
parenchyma, liver floats in formalin.
  TREATMENT
Inpatient Management
• S-CCHS with acute febrile illness , painful 
abdomen, left-shifted leukogram —hydration 
support, “best guess” bactericidal antimicro -
bials: initially based on cytology and Gram 
stain or start trimodal antibiotics, esp. if 
EHBDO or cholecystitis suspected. Antibiotics 
essential before  surgery; continue antibiotics ≥4 
weeks with choleretic therapy until enzymes 
normalize or signs resolve (see Medications).• NS-symptomatic cats —fluid therapy as 
necessary; if jaundiced: vitamin K1 (0.5–
1.5 mg/kg SC/IM q12h for 3 doses) before 
invasive diagnostics; cats with CCHS may 
need blood transfusion consequent to surgery 
or biopsy.
• Polyionic fluids—with B-soluble vitamins 
(2 mL/L), KCl, and K phosphate if refeeding 
syndrome possible; avoid dextrose supplements 
unless hypoglycemia (see Hepatic Lipidosis).
Outpatient Management
• S-CCHS—after acute crisis managed.
• NS-CCHS—after resolution of acute crisis, 
provide lifelong immunomodulation (if no 
bacteria observed or cultured), antioxidants, 
hepatoprotectants.
ACTIVITY
Restricted while symptomatic.
DIET
Nutritional support—avoid FHL in cats by 
feeding balanced high-protein, high-calorie 
feline diet; supplement water-soluble 
vitamins; antigen-restricted diet if 
concurrent IBD; fat-restricted diet if 
steatorrhea due to chronic EHBDO or 
severe ductopenia or chronic pancreatitis 
causing maldigestion; may require feeding 
tube; rarely require parenteral nutrition 
(may provoke FHL).
Emphasize chronic nature of NS-CCHS and 
requirement for lifelong therapy.
• Cholecystectomy—if cholecystitis.
• Cholecystoenterostomy—may be necessary 
for some causes of EHBDO; if choleliths in 
GB: perform cholecystectomy.
Antibiotics: S-CCHS
• Bactericidal—against enteric opportunists; 
initial combination of ticarcillin or clavamox 
with enrofloxacin and metronidazole 
(7.5–15 mg/kg PO q12h; low dose if 
jaundiced).
• Modify initial empiric antimicrobials based 
on culture and sensitivity reports; resistant 
enterococcus may require vancomycin 
(10 mg/kg q12h IV slow infusion for 
7–10 days).
Immunomodulation: NS-CCHS
• Glucocorticoids—prednisolone (dogs: 
2 mg/kg/day prednisone or prednisolone; 
cats: 2–4 mg/kg/day prednisolone only) for 
14–21 days, taper to lowest effective 
alternate-day dose based on ALT and clinical 
signs.(continued)  Cholangitis/Cholangiohepatitis Syndrome

264  Blackwell’s Five-Minute Veterinary Consult  
C• Metronidazole—used for cell-mediated 
immunomodulation, antiendotoxin and 
antibacterial effects, esp. for IBD; as chronic 
bacterial involvement possible in feline 
NS-CCHS, chronic antibiotic treatment may 
be beneficial.
• Cats with confirmed ductopenia—
aggressive immunomodulation; do not use 
azathioprine ; clinical experience suggests 
combination of prednisolone, metronidazole 
with pulsed methotrexate (see below) or 
chlorambucil 1–2 mg per cat, load q24h for 3 
days then every 3 days.
• Methotrexate protocol feline destructive or 
sclerosing NS-CCHS:  0.4 mg total dose  given 
in 3 divided doses on 1 day  (0.13 mg total at 
0, 12, and 24h), repeated at 7–10-day 
intervals), PO/IV/IM (parenteral routes 
require 50% dose reduction); concurrently 
provide folate (folinic acid) 0.25 mg/kg daily. 
If lymphoproliferative or neoplastic infiltrates, 
use chemotherapy protocols developed for 
enteric lymphoma.
• Vitamin E ( α-tocopherol acetate)—  
10 IU/kg), using oral water-soluble form in 
chronic EHBDO or ductopenia (fat 
• S-adenosylmethionine (SAMe)—20 mg/kg/
day enteric-coated tablet PO 2h before 
feeding; benefits include anti-inflammatory 
influence; high dose for glutathione choleresis: 
40 mg/kg/day.
Other
• Ursodeoxycholic acid (UDCA)—10–
15 mg/kg/day PO divided, given with food 
for best bioavailability; provides immuno -
modulatory, hepatoprotectant, choleretic, 
antifibrotic, antioxidant effects; in immune-
mediated NS-CCHS with developing 
ductopenia, use is controversial based on 
work in humans and animal models of 
immune-mediated destructive cholangitis: 
findings indicate may hasten small duct 
injury; liver biopsy recommended before 
prescribing UDCA for cats with “suspected” 
chronic CCHS; taurine supplementation 
(250 mg/day) should be considered in cats 
with poor appetite given chronic UDCA 
because of obligatory bile acid taurine 
conjugation.
• B vitamin supplementation—thiamine (B1) 
and B12: thiamine 50–100 mg PO q24h for 3 
days, then in water-soluble vitamin 
supplements while hospitalized; B12 0.25–
1.0 mg SC if suspect gut malabsorption, 
using initial and sequential plasma B12 concentrations to guide need for chronic 
Adjust drug dosages with regard to liver 
function and cholestasis. Caution with 
metronidazole to avoid neurotoxicity—if 
jaundiced use 7.5 mg/kg PO BID.
  FOLLOW-UP
• S-CCHS—follow body temperature, CBC, 
biochemical profile initially q7–14 days; 
continue antibiotics until clinical features 
normalize; if DPM may require lifelong 
• Animals with intrahepatic cholelithiasis and 
S-CCHS require long-term antibiotics, UDCA, 
high-dose SAMe, and monitoring for 
recurrent sepsis, stone migration (e.g., CBD, 
EHBDO).
• NS-CCHS—initially monitor enzymes 
and bilirubin q7–14 days, then monthly 
for 3 months to judiciously adjust immuno -
modulatory protocol, then quarterly.
• Serum bile acid measurements complicated 
by ursodeoxycholic acid administration and 
superfluous in circumstance of hepatobiliary 
jaundice
• Control IBD.
• If S-CCHS in animals with DPM—
manage long term with appropriate anti -
biotics (see Ductal Plate Malformation).
• If choleliths in CBD or GB—surgically 
intervene: cholecystectomy if GB choleliths; 
flushing CBD free of lithic material essential 
if EHBDO.
• S-CCHS may transform to NS-CCHS or 
sclerosing CCHS.
• Diabetes mellitus develops in ~30% of cats 
with sclerosing CCHS treated with predni  - 
solone.
• FHL may develop due to inadequate 
nutritional intake or as side effect of gluco- 
corticoids.
• S-CCHS—may be cured.
• NS-CCHS—chronic, long-term, vacillating 
illness or remission possible (survival >8 years 
documented in some cats).  MISCELLANEOUS
• Hepatic lipidosis.
• DPM.
• Lymphosarcoma.
• Lymphoproliferative disease.
• Cholangiocarcinoma—may develop in 
some cats with chronic NS-CCHS or DPM.
SEE ALSO
• Ductal Plate Malformation (Congenital 
Hepatic Fibrosis).
• Hepatic Lipidosis.
• Inflammatory Bowel Disease.
• AST = aspartate amino transferase.
syndrome.
• CIN = chronic interstitial nephritis.
• FHL = hepatic lipidosis.
• fPLI = feline pancreatic lipase activity.
• GGT = γ-glutamyltransferase.
• NS-CCHS = nonsuppurative CCHS.
• SAMe = S -adenosylmethionine.
• S-CCHS = suppurative CCHS.
• UDCA = ursodeoxycholic acid.
Pract 2009, 39:543–598.
Warren AE, Center SA, McDonough SE, et al. 
Histopathologic features, immunophenotyp -
ing, clonality and eubacterial FISH in cats 
with nonsuppurative cholangitis/cholangio -
hepatitis. Vet Pathol 2011, 48:627–634.
available onlineCholangitis/Cholangiohepatitis Syndrome  (continued)

Canine and Feline, Seventh Edition  265
CCholecystitis and Choledochitis
 BASICS
OVERVIEW
• Cholecystitis = gallbladder (GB) inflamma-
tion. • Choledochitis = large bile duct 
inflammation. • Associated with cholelithi-
asis; secondary to GB mucocele (GBM); 
extrahepatic bile duct obstruction (EHBDO); 
inflammation of intrahepatic biliary 
structures (common in ductal plate malfor-
mation [DPM]). • Severe GB inflammation 
can lead to rupture and subsequent bile 
peritonitis, necessitating combined surgical 
and medical interventions. • Bile duct 
obstruction increases risk for biliary infection: 
enteric bacteria transmigrate bowel wall, pass 
into portal circulation, disseminate within 
liver, bile, and then GB, dispersing endotox-
ins and bacteria that may cause systemic 
sepsis or septic peritonitis.
• Dog and cat. • No breed or sex predilec-
tion. • Necrotizing cholecystitis (dogs)—usually 
middle-aged or older animals. • GBM— 
predisposition for elderly dogs, dogs with 
hyperlipidemia or hypercholesterolemia (e.g., 
endocrinopathies [hyperadrenocorticism, 
hypothyroidism, diabetes mellitus]), pancrea -
titis, glucocorticoid administration, nephrotic 
syndrome, idiopathic hyperlipidemia (e.g., 
Shetland sheepdogs, miniature schnauzers, 
beagles, others); leads to cholestasis and 
possible cholecystitis (see Gallbladder 
Mucocele).
SIGNS
• Choledochitis—vague signs, variable 
icterus. • Sudden onset—inappetence, 
lethargy, vomiting, vague abdominal pain 
(may be postprandial with cholecystitis or 
GBM, reflecting post-meal GB contraction). 
• Chronic postprandial discomfort/distress—
position of comfort, stretching, pacing, 
panting. • Mild to moderate jaundice and 
fever common. • Severe disease—shock due 
to endotoxemia, bacteremia, hypovolemia.  
• Soft tissue mass in right cranial abdomen 
palpable in small dogs and cats, reflecting 
inflammation or adhesions between GB and 
pericholecystic tissues.
• Impaired bile flow at cystic duct or GB 
(cholelithiasis, mass lesions), GB dysmotility, 
or ischemic insult to GB wall (from GB 
distention)—may precede cholecystitis ± 
necrotizing lesions. • Irritants in sludged bile 
(e.g., lysolecithin, prostaglandins, choleliths, 
flukes) or retrograde flow of pancreatic 
enzyme into bile duct in cats may initiate/
augment GB or duct inflammation.  
• Previous enteric disorders, trauma, 
abdominal surgery—may be contributing 
factors. • Anomalous GB or duct develop -ment—DPM lesions including choledochal 
cysts (cats > dogs). • Bacterial infection—
common; retrograde duct bacterial invasion 
from intestines or hematogenous dispersal 
from splanchnic circulation. • Toxoplasmosis 
and biliary coccidiosis—rare causes. • 
Necrotizing cholecystitis (dogs)—ruptured 
GB (common, often secondary to 
cholelithiasis or hypermature GBM); E. coli  
and Enterococcus  spp.: common isolates.  
• Emphysematous cholecystitis/choledochitis—  
rare, associated with diabetes mellitus, traumatic 
GB ischemia, acute cholecystitis (with or 
without cholelithiasis); common gas-forming 
organisms: Clostridia  spp. and E. coli .
 DIAGNOSIS
• EHBDO. • GBM. • Cholelithiasis.  
• Cholangitis/cholangiohepatitis. • Pancreatitis. 
• Focal or diffuse peritonitis. • Bile peritonitis. 
• Gastroenteritis with biliary involvement.  
• Hepatic necrosis or abscessation. • Septicemia.
• Variable leukocytosis with toxic neutrophils 
and inconsistent left shift if necrosis or sepsis. 
• High bilirubin and bilirubinuria common.  
• High alanine aminotransferase (ALT), 
aspartate aminotransferase (AST), alkaline 
phosphatase (ALP), and γ-glutamyl trans-
ferase (GGT) activity. • Low albumin with 
peritonitis. • High cholesterol and bilirubin if 
EHBDO. • Hypercholesterolemia and/or 
hypertriglyceridemia—breed related, 
endocrine related, pancreatitis, nephrotic 
syndrome, EHBDO, GBM.
• Abdominocentesis—inflammatory effusion 
(see Bile Peritonitis). • Bile culture (dogs and 
cats)— E. coli , Enterococcus  spp., Klebsiella  
spp., Pseudomonas  spp., Clostridium  spp., 
many others. • Coagulation tests—abnormal 
if chronic EHBDO (vitamin K deficiency) or 
in severe conditions with sepsis; cats display 
coagulopathy with EHBDO early.
IMAGING
• Abdominal radiography—may reveal loss of 
cranial abdominal detail with focal or diffuse 
peritonitis or effusion; ileus; radiodense 
choleliths; gas in biliary structures; radiodense 
GB (dystrophic mineralization due to chronic 
inflammation; porcelain GB is rare).  
• Ultrasonography—diffusely thick GB wall, 
segmental hyperechogenicity and/or laminated 
wall or double-rimmed GB wall observed with 
necrotizing cholecystitis; double-rimmed GB 
wall also observed with acute cholecystitis, 
hepatitis, cholangiohepatitis; GB lumen filled 
with amorphous echogenic stellate or finely 
striated pattern, resembling sliced kiwi fruit (“kiwi sign”) in mature GBM; GB rupture 
implicated by discontinuous GB wall, 
pericholecystic fluid, or generalized effusion, 
and hyperechogenicity of pericholicystic 
tissue; failure to image GB: may implicate 
rupture or agenesis; mineralized GB wall may 
indicate dystrophic mineralization (limey or 
porcelain GB) due to chronic cholecystis often 
associated with sacculated GB or bile ducts in 
DPM: Caroli’s phenotype; intrahepatic bile 
ducts may be difficult to visualize or be thick 
and prominent: ascending cholangitis or 
EHBDO (dilated ducts, “too many tubes 
signs” defined with color-flow Doppler); 
pericholecystic fluid: necrotizing cholecystitis 
and surgical emergency. • Choledochitis 
involving common bile duct (CBD)—thick 
wall, intraluminal debris, extends into hepatic 
ducts.
• Gross appearance—erythematous GB; may 
appear green-black if necrotizing lesion; 
tenacious “inspissated” biliary material 
common with GBM; pigmented choleliths if 
infection; dark black or frank blood if 
hemobilia; CBD with thick wall, variable 
intraductal debris (e.g., biliary particulates, 
cholelithiasis, suppurative inflammation).  
• Microscopic features of GBM without 
cholecystitis are benign, with wall thinning, 
mucosal cystic hyperplasia, elongated mucosal 
fronds extending from flattened mucosa, 
without granulation response in GB wall; if 
chronic GBM may involve arterial thrombi 
and/or transformation to chronic cholecysti-
tis. • Microscopic features of cholecystitis 
include inflammatory infiltrates in lamina 
propria (lymphoplasmacytic or suppurative 
with macrophages, rarely eosinophilic, 
occasional lymphoid follicular hyperplasia), 
intraluminal suppurative/necrotic debris; if 
chronic cholecystitis—submucosal 
 granulation tissue with variable ulcerative/
necrotic mucosa, occasional hemobilia, 
occasional arterial thrombi; if cholelithiasis—
hyperplastic mucosa with dense elongated 
mucosal fronds and glands contrasting with 
flattened appearance of GBM.
 TREATMENT
• Inpatient—provision of critical care during 
diagnostic/presurgical evaluations or if septic. • 
Place IV catheter in peripheral vein for 
polyionic fluids and blood component therapy 
as needed. • Restore fluid and electrolyte 
balance; monitor electrolytes frequently. • 
Vitamin K—if jaundiced; give parenterally

 TREATMENT
Vitamin K—if jaundiced; give parenterally 
(see Medications) before surgical interventions, 
cystocentesis, jugular venipuncture, other 
iatrogenic trauma. • Plasma—preferred colloid; 
indicated if hypoalbuminemia and 
coagulopathy or if anticipated surgical

266  Blackwell’s Five-Minute Veterinary Consult  
CCholecystitis and Choledochitis  (continued)
interventions and complicating coagulopathy 
uncorrected. • Whole blood or fresh frozen 
plasma—for surgical cases with bleeding 
tendencies; if septic, artificial colloids may 
delay recovery; if bleeding, some artificial 
colloids impair platelet aggregation. • Monitor 
urine output. • Remain vigilant for vasovagal 
reflex (abrupt bradycardia, hypotension, 
cardiac arrest) during biliary tree manipulation 
or cholecystocentesis; be prepared with 
anticholinergics (atropine) and pressor drugs. 
• Remain vigilant for cholangiovenous 
reflux—systemic dispersal of endotoxin or 
bacteria while handling septic biliary tree: give 
IV antibiotics promptly (but after culture 
collection). • GB resection advised for 
cholecystis, best based on surgical evaluations, 
ultrasound images, bedside cytology of 
bile—bacterial infection mandates cholecystec  - 
tomy.
• Antibiotics— before surgery ; broad spectrum; 
surgical manipulations may cause bacteremia; 
select antibiotics for Enterococcus  spp., enteric 
Gram-negative and anaerobic flora; refine 
treatment using culture and sensitivity results; 
good initial choice is triad combination of 
metronidazole, ticarcillin (or clavamox), and a 
fluorinated quinolone; reduce standard dose 
for metronidazole by 50% if cholestatic 
jaundice. • Ursodeoxycholic acid—10–15 mg/
kg PO daily divided BID with food; requires 
decompression of EHBDO prior to treatment . 
• Antioxidants—vitamin E ( α-tocopherol 
acetate): 10 IU/kg (see Bile Duct Obstruction 
(Extrahepatic); use water-soluble form if 
EHBDO); S-adenosylmethionine (SAMe): 
use enteric-coated bioavailable product; on 
empty stomach: used as glutathione (GSH) 
donor (20 mg/kg PO q24h), 2h before feeding; nonbile acid-dependent (GSH) 
choleresis (40 mg/kg PO q24h); n-acetyl -
cysteine (NAC) IV if oral administration of 
antioxidants not possible; loading dose 
140 mg/kg IV over 20 min, follow by 70 mg/
kg over 20 min q6–8h. • Vitamin K1—0.5–
1.5 mg/kg SC/IM q12h for 3 doses; caution : 
never administer IV (anaphylactoid reaction); 
treat early to allow response before surgical 
manipulations.
Ursodeoxycholic acid—contraindicated in 
uncorrected EHBDO or bile peritonitis.
 FOLLOW-UP
• After critical crisis resolution and surgery—
physical examination and pertinent diagnostic 
testing: repeat every 1–2 weeks until abnorm  - 
alities resolve. • If septic—continue anti -
biotics until enzymes, hyperbilirubinemia, 
leukocytosis, left shift, and fever resolve.
Anticipate protracted clinical course with 
ruptured biliary tract or peritonitis; postop-
erative pancreatitis.
• Cholelithiasis. • DPM. • EHBDO. • GBM. 
Congenital malformations of biliary 
structures do not predispose patients to 
cholecystitis, but do predispose to 
choledochitis and cholelithiasis that lead to 
GB disease and infection.ZOONOTIC POTENTIAL
Campylobacter  and Salmonella  may cause 
cholecystitis in dogs; advise owner if 
SEE ALSO
• Bile Peritonitis.
• AST = aspartate aminotransferase. 
•  EHBDO = extrahepatic bile duct 
• NAC = n-acetylcysteine.
Lawrence YA, Ruaux CG, Nemanic S, et al. 
Characterization, treatment, and outcome 
of bacterial cholecystitis and bactibilia in 
dogs. J Am Vet Med Assoc 2015, 
246:982–989.
Tamborini A, Jahns H, McAllister H, et al. 
Bacterial cholangitis, cholecystitis, or both 
in dogs. J Vet Intern Med 2016, 
30:1046–1055.

Canine and Feline, Seventh Edition  267
CCholelithiasis
 BASICS
OVERVIEW
• Radiopaque or radiolucent calculi in 
common bile ducts (CBD), gallbladder (GB), 
or less commonly in intrahepatic bile ducts 
(hepatolithiasis); gallbladder mucocele 
(GBM) qualifies as a form of cholelithiasis 
(see Gallbladder Mucocele).
• May be asymptomatic.
• Symptomatic—signs reflect sludging of 
bile, extrahepatic bile duct obstruction 
(EHBDO), cholecystitis, cholangiohepatitis, 
or bile peritonitis.
• Primary constituents of choleliths—mucin, 
glycoprotein, calcium carbonate, and 
bilirubin pigments; while dog bile is less 
lithogenic than human bile (lower cholesterol 
saturation), dog bile forms calcium bilirubi-
nate sludge upon fasting.
• 50% feline choleliths are mineralized; may 
be radiographically visible (calcium carbonate).
• Surgical treatment—not recommended 
without clinical signs or clinicopathologic 
abnormalities (current or historical), with the 
exception of preemptive GBM removal.
• Cat and dog.
• Small-breed dogs may be predisposed; 
animals with ductal plate malformations 
(DPM) predisposed: particularly Caroli DPM 
phenotypes (i.e., malformative dilated large 
ducts causing bile stasis in sacculated ducts); 
microhepatolithiasis encountered more often 
in DPM.
• Hyperlipidemic and hypercholesterolemic 
dogs—predisposed to GBM; may relate to 
endocrine disorders, idiopathic condition, or 
other disorders (see Gallbladder Mucocele).
SIGNS
• When accompanied by infection or causing 
intermittent or complete EHBDO (with or 
without peritonitis)—vomiting; meal-related 
discomfort, vague abdominal pain; fever;  
± jaundice.
• Episodic vague peri- or postprandial 
abdominal pain or behavior seeking position 
of relief.
• Predisposing factors—stasis of bile flow: 
GB dysmotility, choledochal cysts (cat 
especially, form of DPM); lith nidus may 
evolve from inflammatory debris, infection, 
epithelial irregularity/exfoliation, neoplasia, 
residual suture material; bile supersaturation: 
heme-bilirubin pigments, hemobilia, 
calcium-bilirubinate, enhanced mucin 
production (inflammation, prostaglandins), 
cholesterol.• Fused feline pancreatic and bile duct 
predisposes to concurrent biliary/pancreatic 
cholelithiasis, choledochitis, and bile stasis 
progressing to EHBDO as well as cholelith-
initiated pancreatitis or signs mistaken for 
• Bile sludge associated with GB distention—
may enhance mucin production and 
coalescence of bile particulates increasing risk 
for choleliths; but EHBDO does not cause 
choleliths.
• Inflammatory mediators and bacterial 
enzymes associated with cholecystitis—
increase risk for stone precipitation.
• Hemobilia—bleeding into GB or bile ducts 
or chronic hemolysis can lead to heme-  
initiated cholelith formation.
• Low-methionine and high-cholesterol 
experimental diet in dogs is proven lithogenic.
 DIAGNOSIS
• EHBDO—inflammatory, infectious, or 
neoplastic conditions involving liver, CBD, or 
extrahepatic tissues adjacent to porta hepatis; 
suggested by marked increases in alkaline 
phosphatase (ALP), γ-glutamyltransferase 
(GGT), bilirubin, and gradual increase in 
cholesterol.
• Cholangiohepatitis.
• Cholecystitis/choledochitis.
• GBM.
• Consequence of DPM.
• Chronic hypercalcemia may increase risk.
• May have no clinicopathologic  
abnormalities—asymptomatic cholelithiasis.
• CBC—may be normal; may reflect bacterial 
infection, endotoxemia, biliary obstruction, or 
other underlying causal factors; inflammatory 
leukogram in some cases.
• Biochemistry—if symptomatic: variable 
hyperbilirubinemia, increase ALP , GGT, 
alanine aminotransferase (ALT), and aspartate 
aminotransferase (AST) activities; also see 
Bile Duct Obstruction (Extrahepatic).
• Bacterial culture—bile: aerobic and 
anaerobic bacteria often confirmed in 
symptomatic patients if crushed cholelith, 
sludged bile, ± GB wall (if cholecystectomy) 
submitted for cultures.
• Cholelith nidus—may house associated 
bacterial infection.
• Coagulation profile—bleeding associated 
with prolonged clotting times may develop 
with EHBDO of >7–10 days; see Bile Duct 
Obstruction (Extrahepatic); responsive to 
parenteral vitamin K1 administration.• Cholelith analysis—infrequently done; 
submit to laboratory equipped for cholelith 
analyses.
IMAGING
• Abdominal radiography—limited value in 
delineating GB structure/content; choleliths 
often small, may be radiolucent; rarely 
mistaken for dystrophic biliary mineralization 
in animals with chronic cholangitis or Caroli 
DPM phenotype.
• Ultrasonography—can detect: choleliths 
≥2 mm diameter, thickened GB wall, 
distended biliary tract, increased hepatic 
parenchymal echogenicity and extrahepatic 
ductal involvement; may facilitate specimen 
collection for culture, cytology, and histopa-
thology; may detect evidence of EHBDO 
within 72h; caution : distended GB with bile 
“sludge” is common in anorectic or fasted 
patients; do not mistake for GB obstruction. 
Hepatolithiasis usually casts acoustic shadows. 
Imaging of choleliths within extrahepatic 
ducts may be difficult owing to enteric gas 
obstructing imaging “window”; confirmation 
of distended intrahepatic bile duct done with 
color-flow Doppler.
Histopathologic evaluation of liver necessary 
in patients undergoing surgical cholelith 
removal to detect comorbid conditions 
influencing treatment and prognosis,  
i.e., suppurative cholangitis, nonsuppurative 
cholangitis, DPM, neoplasia.
 TREATMENT
• Controversial whether choleresis with 
ursodeoxycholate (UDCA) is beneficial in 
animals lacking clinical or clinicopathologic 
signs; can resolve cholesterol choleliths in 
humans, but these are rare in dogs or cats; 
choleresis with UDCA may help move 
sludged biliary debris.
• Supportive fluids—if hospitalized, 
according to hydration, electrolyte, and 
acid-base status.
• If hyperlipidemia coexistent—prescribe 
fat-restricted diet, identify and manage 
endocrinopathies; if failure to control 
hyperlipidemia, may require additional 
• Control predisposing conditions, especially 
biliary tree infection (with antimicrobials) 
and GB dysmotility (by GB removal).
• Exploratory surgery, choledochotomy, 
cholecystotomy, and possibly cholecystectomy 
or biliary-enteric anastomosis—indicated in 
symptomatic cases according to circumstances.
• Warn client that cholelithiasis is chronic 
problem and that stones may reform even 
after surgical removal despite chronic medical 
treatment; choleliths in GB is strong

268  Blackwell’s Five-Minute Veterinary Consult  
CCholelithiasis  (continued)
indication for cholecystectomy unless GB 
needed for biliary enteric anastomosis in 
certain conditions.
• Antibiotics—based on culture of bile, 
tissue, and cholelith nidus, cytology and 
Gram staining of biliary debris or crushed lith 
if cultures negative; if culture negative then 
directed against enteric microbial opportun-
ists; initial treatment with Timentin or 
Clavamox® with metronidazole, combined 
with a fluoroquinolone, usually successful.
• Ursodeoxycholic acid—10–15 mg/kg/day 
PO, divided BID, given with food to increase 
bioavailability; provides choleretic, hepato-
protectant, anti-endotoxic, antifibrotic effects, 
and may facilitate cholesterol stone dissolu-
tion; therapy often continued lifelong if no 
cause for cholelithiasis identified to augment 
choleresis thwarting bile stasis.
• Vitamin K1—parenterally; 0.5–1.5 mg/kg 
to max 3 doses in 24–36h in jaundiced 
patients; do not administer IV (anaphylaxis).
• Vitamin E ( α-tocopherol acetate)—10 IU/kg 
per day for patients with high liver enzymes 
or confirmed hepatobiliary inflammation; use 
water-soluble form if EHBDO.
• S-adenosylmethionine (SAMe; use form 
with proven bioavailability and efficacy)— 
glutathione (GSH) donor (important 
hepatic antioxidant, GSH also provides 
driving force for non-bile acid–dependent choleresis) and thus is potential choleretic 
for patients with high liver enzymes or 
confirmed hepatobiliary inflammation; 
20–40 mg/kg using enteric-coated tablet PO 
q24h, administer 2h before feeding; higher 
dose recommended for choleresis; also 
provides antifibrotic and antiinflammatory 
benefits.
Ursodeoxycholic acid—contraindicated with 
EHBDO before biliary decompression.
 FOLLOW-UP
• Physical examination and pertinent 
diagnostic testing q2–4 weeks postoperatively 
until clinical signs and clinicopathologic 
abnormalities resolve.
• Periodic ultrasonography—assess cholelith 
status, integrity/distention of biliary tract, 
hepatic parenchymal changes.
Sudden onset of fever, abdominal pain, and 
malaise—may signify bile peritonitis and/or 
sepsis from breakdown in bile containment, 
or recurrent cholelith lodged in sphincter of 
Oddi (duodenal papilla) or obstructing 
pancreatic duct (cats only).
• Symptomatic disease—reflects existing 
infection, EHBDO, cholecystitis, DPM, or 
bile peritonitis. MISCELLANEOUS
SEE ALSO
• UDCA = ursodeoxycholate.
van Geffen C, Savary-Bataille K, Chiers K, 
et al. Bilirubin cholelithiasis and haemosi-
derosis in an anaemic pyruvate kinase-
deficient Somali cat. J Small Anim Pract 
2008, 49:479–482.

Canine and Feline, Seventh Edition  269
CChondrosarcoma, Bone
 BASICS
OVERVIEW
• Chondrosarcoma (CSA) is a malignant 
mesenchymal tumor arising from cartilage and 
characterized by production of chondroid and 
fibrillar matrix. • CSA is the second most 
common primary bone tumor in dogs and 
accounts for 5–10% of all primary bone tumors; 
primary bone tumors are uncommon in cats, and 
CSA is third in incidence behind osteosarcoma 
and fibrosarcoma. • Dogs—majority of CSAs 
arise from flat bones (axial skeleton); approxi -
mately 30% occur in nasal cavity and 20% of 
CSAs arise from ribs; 20% of CSAs in dogs arise 
from appendicular skeleton; sites are generally 
similar to where osteosarcoma typically occurs.  
• Cats: 66% of CSAs arise in appendicular skeleton, 
with 33% occurring in the axial skeleton. • Rarely, 
CSA can arise in soft tissue (extraskeletal) sites.
• Dogs—medium- to large-breed dogs, with 
mixed-breed dogs, golden retrievers, boxers, 
and German shepherd dogs overrepresented; 
median age is 8 years (range: 1–15 years).  
• Cats—median age is 9 years (range: 2–18 
years), with males twice as likely to be affected.
SIGNS
• Patients often present with a visible mass at 
the affected site. • History of lameness if 
involvement of weight-bearing bone. • Rarely, 
CSA of the rib may be associated with 
respiratory signs. • Additional clinical signs 
vary with site of involvement.
• Findings depend on anatomic location.  
• A firm to hard mass often is palpable, with 
variable degrees of pain elicited on palpation. 
• CSA of the rib occurs most commonly at 
the costochondral junction; dyspnea is rare 
and associated with space-occupying effect.
• Etiology largely unknown.  
• Osteochondromatosis (multiple cartilaginous 
exostosis) lesions can transform into CSA.
 DIAGNOSIS
• Other primary bone tumors (osteosarcoma, 
fibrosarcoma, hemangiosarcoma).  
• Metastatic bone tumors (transitional cell, 
prostatic, mammary, thyroid, apocrine gland, 
anal sac carcinomas). • T umors that locally 
invade adjacent bone (especially oral, nasal, 
digital, and joint tumors). • Fungal osteomyelitis.CBC/BIOCHEMISTRY/URINALYSIS
IMAGING
• Radiographs of affected area show features 
of aggressive bone lesion (cortical lysis, 
nonhomogenous reactive bone formation, 
ill-defined zone of transition). • Thoracic 
radiographs recommended to screen for 
pulmonary metastasis. • CT recommended 
for axial tumors to more accurately stage local 
disease and plan for surgery and/or radiation 
therapy; concurrent CT imaging of thorax 
recommended as more sensitive way to screen 
for pulmonary metastasis. • MRI, alone or in 
combination with CT, may be recommended 
for treatment planning for vertebral CSA.
• Histopathology needed for definitive diagnosis. 
• Fine-needle aspirate bone cytology may provide 
supportive diagnosis; differentiation of CSA 
from other sarcomas may be challenging if 
sample contains sparse amounts of matrix.
 TREATMENT
• Amputation recommended for appendicu-
lar tumors. • For axial tumors, wide surgical 
excision recommended whenever possible.  
• Stereotactic radiation therapy provides 
effective local control for canine osteosarcoma 
and might be alternative to surgery for 
patients with CSA. • Palliative therapy 
recommended for patients with nonresectable 
local disease or gross metastasis, or when 
definitive therapy is declined; palliative care 
focuses on pain control.
Pain Management
(NSAIDs). • T ramadol. • Gabapentin. • IV 
aminobisphosphonates (e.g., pamidronate, 
zoledronate) might alleviate bone pain and 
slow pathologic bone resorption.
Role of chemotherapy has not been defined 
in veterinary oncology, but does not
improve outcome in humans.
• Use NSAIDs cautiously in all cats and in 
dogs with renal insufficiency. • Do not 
combine NSAIDs with corticosteroids. FOLLOW-UP
Physical examination every 2–3 months and 
thoracic radiographs every 3–4 months to 
monitor for local tumor control and distant 
metastases, respectively.
• Overall, 15–30% of dogs will develop 
metastatic disease, with lungs being most 
commonly affected site; metastatic rates 
approach 50% for high-grade canine tumors; 
development of metastasis rare for cats with 
CSA. • With curative-intent surgery, median 
survival >3 years; depending on tumor 
location and completeness of excision, up to 
40% will develop local recurrence. • With 
palliative care alone, survival times of >1 year 
still possible.
SEE ALSO
• Chondrosarcoma, Oral. 
• Fibrosarcoma, Bone.
• Osteosarcoma.
• CSA = chondrosarcoma.
drug.
Durham AC, Popovitch CA, Goldschmidt 
MH. Feline chondrosarcoma: a retrospec-
tive study of 67 cats (1987–2005). J Am 
Anim Hosp Assoc 2008, 44(3):124–130.
Farese JP , Kirpensteijn J, Kik M, et al. 
Biologic behavior and clinical outcome of 
25 dogs with canine appendicular chondro-
sarcoma treated by amputation: a Veterinary 
Society of Surgical Oncology retrospective 
study. Vet Surg 2009, 38:914–919.
Author  Jenna H. Burton
Dennis B. Bailey.

270  Blackwell’s Five-Minute Veterinary Consult  
CChondrosarcoma, Nasal and Paranasal Sinus
 BASICS
OVERVIEW
mesenchymal tumor arising from cartilage 
and characterized by production of chondroid 
and fibrillar matrix. •  Nasal CSA arises most 
commonly from the nasal turbinates. •  In dogs, 
CSA accounts for 15% of all nasal tumors.
• Mixed-breed dogs, Labrador retrievers, 
golden retrievers, boxers, and German 
shepherd dogs are overrepresented. •  Median 
age is 7 years (range: 2–13 years). •  CSA 
tends to develop at a younger age than other 
nasal tumors. •  Rare in cats, with no obvious 
breed or sex predilections.
SIGNS
• Intermittent unilateral epistaxis and/or 
mucopurulent discharge, may progress to 
bilateral involvement. •  Sneezing, stertorous 
breathing, and/or facial deformity. •  Decreased 
appetite and/or halitosis secondary to oral cavity 
invasion. •  Seizures, behavior changes, and/or 
obtundation secondary to cranial invasion.
• Epistaxis and/or nasal discharge, initially 
unilateral but can progress to bilateral. 
• Decreased nasal air flow (unilateral or 
bilateral). •  Pain on nasal or paranasal sinus 
palpation or percussion. •  Facial deformity, 
decreased ocular retropulsion, exophthalmia, 
or epiphora. •  Visible mass effect protruding 
through the palate into the oral cavity.
Unknown
 DIAGNOSIS
• Other nasal tumors—adenocarcinoma, 
squamous cell carcinoma, osteosarcoma, 
fibrosarcoma, lymphoma, transmissible 
venereal tumor (dogs), nasopharyngeal polyp 
(cats). •  Fungal rhinitis—aspergillosis and 
penicilliosis (dogs), cryptococcus (cats), 
sporotrichosis (both). •  Rhinosporidiosis 
(dogs). •  Foreign body. •  Thrombocytopenia 
or other coagulopathy. •  Tooth root abscess. 
Usually normal—evaluate for thrombocyto-
penia if signs of epistaxis.
• Nasal flush for cytology and culture—rarely 
helpful. •  Coagulation profile. •  Buccal 
mucosal bleeding time.IMAGING
• Thoracic radiographs to screen for 
pulmonary metastasis (uncommon). •  CT 
for detecting soft tissue opacity within nasal 
cavity and surrounding sinuses, bony 
destruction, and extension through cribriform 
plate into brain. •  If CT scan is not 
accessible, skull radiographs can be performed 
to assess for soft tissue opacity in nasal cavity 
and/or frontal sinuses.
• Blood pressure, to rule out systemic hyper  - 
tension as cause for epistaxis. •  Mandibular 
lymph node cytology to screen for possible 
metastasis. •  Rhinoscopy is helpful for 
visualization of mass or fungal plaque and 
guiding subsequent tissue biopsy. •  Tissue 
biopsy and histopathology needed for 
definitive diagnosis; biopsy instrument should 
not pass caudal to level of medial canthus of 
eye to avoid penetrating cribriform plate. 
• Intranasal approach to obtaining tissue 
biopsy preferable if treatment radiation 
therapy planned.
 TREATMENT
• Radiation therapy is treatment of choice. 
• Conventional linear accelerator used most 
commonly; however, if available, stereotactic 
radiation therapy can reduce number of 
radiation treatments and reduce adverse 
effects. •  Palliative radiation protocols (fewer 
treatments and lower total radiation dose) 
might be preferable for dogs with very 
advanced disease.
(NSAIDs) for pain control. •  Prednisone 
(0.5–1 mg/kg PO q24h) to help relieve nasal 
congestion. •  Phenylephrine nasal spray can 
be used intermittently to help with epistaxis. 
• Empiric antibiotic therapy can be 
considered for secondary bacterial infections.
dogs with renal insufficiency. •  Do not 
combine NSAIDs with corticosteroids.
 FOLLOW-UP
• Physical examinations every 2–3 months 
and thoracic radiographs every 3–4 months. • CT of skull can be considered when clinical 
signs recur or progress.
• <10% develop metastasis (lungs affected 
most commonly). •  Median survival with 
palliative care alone is 3 months. •  With 
definitive daily radiation therapy, median 
survival is around 17 months, and 2-year 
survival rate is around 30%; median survival 
with palliative radiation protocols is about 9 
months. •  Recurrence/progression of tumor 
and recurrence of clinical signs generally 
life-limiting event for nasal CSA. •  Brain 
involvement is poor prognostic sign. 
• Unilateral versus bilateral involvement is 
not significant prognostic factor.
SEE ALSO
• Adenocarcinoma, Nasal.
• Chondrosarcoma, Bone.
• Chondrosarcoma, Oral.
drug.
Patnaik AK, Lieberman PH, Erlandson RA, 
et al. Canine sinonasal skeletal neoplasms: 
chondrosarcomas and osteosarcomas. Vet 
Pathol 1984, 21(5):475–482.
Sones E, Smith A, Schleis S, et al. Survival times 
for canine intranasal sarcomas treated with 
radiation therapy: 86 cases (1996–2011). Vet 
Radiol Ultrasound 2013, 54(2):194–201.

Canine and Feline, Seventh Edition  271
CChondrosarcoma, Oral
 BASICS
OVERVIEW
and fibrillar matrix.
• CSA accounts for 5–10% of all primary 
bone tumors; mandibular and maxillary CSAs 
have been reported in dogs, but these are not 
common locations for this tumor (see 
Chondrosarcoma, Bone, and 
Chondrosarcoma, Nasal and Paranasal Sinus).
median age is 8 years (range: 1–15 years).
• Cats—rarely affected.
SIGNS
• Visible mass involving the mandible or 
maxilla.
• Halitosis, dysphagia, and/or hypersalivation.
• Bloody oral discharge and oral pain.
• Weight loss secondary to a prolonged 
decrease in food intake.
• A firm to hard mass centered on the maxilla 
or mandible is seen most commonly.
• The overlying gingival mucosa usually is 
intact, although trauma and ulceration from 
the occlusal teeth are common with larger 
tumors.
• Loose or missing teeth.
• Difficulty or pain when opening the mouth 
(especially caudal tumors).
• Facial deformity.
• Mandibular lymphadenopathy.
• Nasal discharge, epistaxis, or decreased air 
flow through the nares (maxillary tumors).
 DIAGNOSIS
• Other primary oral tumors, including 
melanoma, fibrosarcoma, squamous cell 
carcinoma, osteosarcoma, and acanthomatous 
ameloblastoma.
• Maxillary invasion of primary nasal CSA.
• Craniomandibular osteopathy.
• Dentigerous cyst, tooth root abscess, or 
osteomyelitis.
Usually normal.IMAGING
• Thoracic radiographs are recommended to 
screen for pulmonary metastasis.
• Skull radiographs often will show features 
of an aggressive bone lesion (bone lysis, cortical 
destruction, nonhomogenous bone forma-
tion, ill-defined zone of transition); however, 
normal radiographs do not exclude bone 
• High-detail dental radiographs may be 
appropriate for imaging smaller lesions.
• CT imaging can more accurately determine 
extent of local disease and is useful for 
surgical planning, particularly caudal lesions; 
CT is generally required for radiation therapy 
planning.
• Fine-needle aspiration (FNA) and cytology 
of the mass may provide provisional 
diagnosis. FNA and cytology are recom-
mended for mandibular lymph nodes, 
especially if they are enlarged.
• Histopathology is required to reach a 
definitive diagnosis; preoperative incisional 
biopsy is recommended.
• If curative-intent surgery is performed, all 
excised tissue should be submitted to the 
pathologist en bloc  for evaluation of surgical 
margin.
 TREATMENT
• Surgical excision—removal of the affected 
segment of bone (maxillectomy or man-
dibulectomy) with a margin of at least 2 cm is 
recommended whenever possible.
• If excision is incomplete, adjuvant radiation 
therapy might help improve local control, 
although there is little information regarding 
efficacy.
• Radiation therapy can be considered as a sole 
local treatment modality but, because of the 
chondroid matrix produced by CSAs, radiation 
therapy likely will stabilize tumor size and not 
necessarily cause substantial shrinkage.
• Chemotherapy has not been evaluated, but 
is not thought to be effective.
• Palliative care focuses on pain control.
• Nonsteroidal anti-inflammatory drugs.
• T ramadol.
• Gabapentin.
• Intravenous aminobisphosphonates 
(pamidronate or zoledronate) might alleviate 
bone pain and attenuate bone resorption.
• Empiric antibiotic therapy can be consid-
ered for secondary bacterial infections. FOLLOW-UP
Physical examination with thorough oral 
examination every 2–3 months and thoracic 
radiographs every 3–4 months to monitor for 
local tumor control and distant metastases, 
• Prognosis depends on tumor size and location, 
and surgical resectability; with complete excision, 
long-term control may be possible.
• Most patients die or are euthanized due to 
local disease progression.
• Overall CSA metastatic rate is 15–30%, 
with the lungs being affected most com-
monly; metastatic rates approach 50% for 
high-grade tumors.
SEE ALSO
• FNA = fine-needle aspiration.
Verstraete FJ. Mandibulectomy and maxillec-
tomy. Vet Clin North Am Small Anim Pract 
2005, 35(4):1009–1039.
Waltman SS, Seguin B, Cooper BJ, Kent M. 
Clinical outcome of nonnasal chondrosar-
coma in dogs: thirty-one cases (1986–
2003). Vet Surg 2007, 36:266–271.

272  Blackwell’s Five-Minute Veterinary Consult  
CChorioretinitis
 BASICS
• Inflammation of the choroid and retina.
• Choroid is also called posterior uvea.
• Diffuse inflammation may result in retinal 
detachment.
• Caused by infectious agents, neoplastic 
cells, or immune complexes (immune-  
mediated diseases); hematogenous pathogenic 
factors inducing choroidal inflammation is 
most common.
• Choroid and retina—closely apposed; 
physiologically interdependent; inflammation 
of one usually results in inflammation of the 
other.
• May also occur as a retinochoroiditis— 
retinal inflammation preceding and inducing 
choroidal inflammation.
• Nervous.
• Other systems if underlying disease is 
systemic.
• Fairly common.
• Exact incidence unknown.
Varies with endemic infectious diseases  
(e.g., systemic mycoses, rickettsial disease).
Species
• Systemic mycoses—more common in 
hunting dogs.
• Uveodermatologic syndrome—Akita, chow 
chow, and Siberian husky predisposed.
• Chorioretinopathy—borzoi, border collie, 
beagle, German shepherd dog.
• Systemic histiocytosis—Bernese mountain 
dog, golden retriever.
Depends on underlying cause.
Uveodermatologic syndrome—more 
common in young male dogs.
SIGNS
• Not usually painful, except with concurrent 
anterior uveitis, secondary glaucoma, or 
inflammatory retrobulbar disease.
• Vitreous abnormalities—may note exudate, 
hemorrhage, or syneresis (liquefaction).
• Interruption or alteration of the course of 
retinal blood vessels—due to retinal 
elevation.
• Ophthalmomyiasis (cats)—curvilinear 
tracts from migrating larvae.• Others—related to underlying systemic 
disease, retrobulbar disease.
Lesions
• Active—indistinct margins, tapetal hypo  - 
reflectivity, white-gray color, altered course of 
retinal blood vessels.
• Few or small lesions—no apparent visual 
deficits.
• Extensive lesions involving larger areas of 
the retina—blindness or reduced vision.
• Inactive (scars)—discrete margins, tapetal 
hyperreflectivity with hyperpigmented central 
areas, depigmented in the nontapetum and 
some surrounding or central hyperpig  - 
CAUSES
Dogs
• Viral—canine distemper, herpesvirus (rare, 
usually neonates), rabies.
• Bacterial—leptospirosis, brucellosis, 
pyometra (toxic uveitis), borreliosis , ehrlich  - 
iosis, Rocky Mountain spotted fever, 
bartonellosis; discospondylitis, endocarditis 
may be present with bacteremia.
• Fungal—aspergillosis, blastomycosis, 
coccidioidomycosis, histoplasmosis, crypto-
coccosis, acremoniosis, pseudallescheriasis, 
candidiasis, geotrichosis.
• Algal—protothecosis.
• Protozoal—toxoplasmosis, leishmaniasis 
(rare), neosporosis, and sarcocystosis (dogs).
• Parasitic—ocular larval migrans ( Strongyles , 
Ascarids , Baylisascaris ), Sarcocystis neurona , 
and ophthalmomyiasis interna (Diptera larval 
migrans).
• Retrobulbar abscess/cellulitis—uncommon.
Cats
• Viral—feline leukemia virus (FeLV), feline 
infectious peritonitis (FIP).
• Bacterial—septicemia or bacteremia, 
bartonellosis.
• Fungal—cryptococcosis, histoplasmosis, 
blastomycosis.
• Parasitic—toxoplasmosis, ophthalmomyia-
sis interna (Diptera, Cuterebra), ocular larval 
migrans, leishmaniasis (rare).
• Protozoal—toxoplasmosis.
• Common.
• Multifocal chorioretinitis or chorioretin-
opathy—acquired syndrome; affected dogs 
have multifocal retinal edema or chorioretinal 
atrophy.
• German shepherd dog—choroidal scars in 
police dogs: possibly due to physical exertion 
or circulatory disorders; affected dogs had 
lower amplitude ERG.
Immune
• Any immune-mediated disease may cause 
vasculitis or inflammation, resulting in 
exudative retinal detachment or chorioretinitis. Thrombocytopenia may result 
in small multifocal or large retinal or vitreal 
hemorrhages with inflammation.
• Dogs—Vogt-Koyanagi-Harada-like 
(uveodermatologic) syndrome: target is 
melanin pigment granule (abundant in uveal 
tissue), leading to severe anterior and 
posterior inflammation (affected dogs may 
also exhibit depigmentation of the skin, 
especially at mucocutaneous junctions); 
systemic lupus erythematosus (SLE).
• Cats—periarteritis nodosa, SLE.
Metabolic
Early hypertensive retinopathy may result in 
multifocal localized lesions.
Neoplasia (multiple myeloma, lymphoma, 
malignant histiocytosis) can metastasize to the eye.
Toxic
• Ethylene glycol, idiosyncratic drug reactions 
(e.g., trimethoprim-sulfa), ivermectin.
• Photic injury—exposure to bright light can 
burn the retina.
Trauma
Perforating wound or migrating foreign body.
• FeLV or FIV infection—may predispose cat 
to ocular toxoplasmosis or other infectious 
disease.
• Immunosuppressive therapy.
 DIAGNOSIS
• Blindness or impaired vision—optic 
neuritis, CNS disease, diffuse retinal 
• Retinal dysplasia—bilateral, symmetric 
folds or geographic clumps of pigment or 
altered fundus reflectivity; no associated signs 
of inflammation in the eye.
Normal if problem confined to the eye, 
otherwise may have signs of systemic disease.
• Anti-nuclear antibody (ANA)—for 
suspected SLE.
• Bence-Jones proteinuria—for multiple 
myeloma.
• Skin biopsy—SLE, uveodermatologic 
syndrome.
• Coagulation profile.
• Bacterial culture of ocular or body fluids.
• Serologic or PCR testing—infectious 
disease (see Causes).
• Cytology of lymph node, mass, or organ 
aspirates.
• Histopathology of enucleated eyes.
• Bartonella—PCR, culture on special media 
(BAPGM).

Canine and Feline, Seventh Edition  273
C(continued)  Chorioretinitis
IMAGING
• Thoracic radiography—may show 
infectious or neoplastic disease.
• Spinal radiography— may show discospon-
dylitis or multiple myeloma.
• Ocular ultrasound—retinal detachment, 
intraocular masses; especially helpful if the 
ocular media are not clear; can identify 
retrobulbar disease.
• Abdominal ultrasound—screen for 
neoplasia, systemic disease.
• CT/MRI—if signs of retrobulbar or CNS 
disease.
• Indirect ophthalmoscopy—screens a large 
area of the retina.
• Direct ophthalmoscopy—facilitates 
examination of suspicious areas.
• Cerebrospinal fluid (CSF) tap—indicated 
for diagnosis of some CNS disease or optic 
neuritis.
• Vitreocentesis or subretinal aspirate—if 
other diagnostic tests fail or to identify 
infectious agent or neoplasia; vitreocentesis 
may worsen inflammation or induce 
hemorrhage or retinal detachment, reducing 
chances for restoration of vision.
• Choroidal aspirate—of thickened areas, 
ideally ultrasound guided; procedure may 
aggravate inflammation, induce hemorrhage 
or retinal detachment.
• Measurement of blood pressure.
• Masses or retinal or choroidal exudates.
• Fungal organisms in exudates and 
inflammatory cells.
• Perivascular inflammation with vasculitis, FIP .
• Inactive lesions—retinal and choroidal atrophy 
(thinning); may note retinal pigment epithelium 
hyperpigmentation and tapetal destruction.
 TREATMENT
Depends on physical condition of patient, 
usually outpatient.
Therapy for systemic disease, depending on 
patient status.
• Chorioretinitis may be a sign of systemic 
disease, so diagnostic testing is important.
• Immune-mediated disease requires lifelong 
therapy.
• Dogs with uveodermatologic syndrome 
may have anterior uveitis and secondary glaucoma, which necessitate treatment or eye 
removal; dermatitis may also require management.
• Identify and treat underlying systemic 
disease (see specific chapters).
• Topical medications—not effective in dogs 
with intact lenses; systemic therapy required.
◦ 1% prednisolone acetate or 0.1% 
dexamethasone q6–8h to treat anterior uveitis.
◦ Parasympatholytics (e.g., 1% atropine) 
can be given at a frequency that dilates the 
pupil and reduces pain.
◦ 0.5% timolol maleate or 2% dorzolamide 
may be used to treat secondary glaucoma.
• Corticosteroids at anti-inflammatory 
doses—prednisone 0.5–1 mg/kg PO q24h 
(dog), prednisolone 1–2 mg/kg q24h (cat), 
then taper; avoid use unless large areas of the 
retina are affected and vision is severely threatened.
• Prednisone for immunosuppression— 
2–4 mg/kg PO divided q12 for 3–10 days 
(dog, cat), then taper slowly over months (do 
not exceed 80 mg per day).
Systemically administered corticosteroids—do 
not use if systemic infectious disease is present. 
Exception: sometimes steroids are used when 
infectious cause has been identified and is 
being treated.
Uveodermatologic syndrome or known 
autoimmune etiology—may require corticoster -
oids and concurrent use of or transition to other 
immunosuppressive medications (e.g., 
azathioprine, cyclosporine, leflunomide, or 
mycophenolate mofetil; see Retinal Detachment).
 FOLLOW-UP
• As appropriate for underlying cause and 
type of medical treatment.
• For bartonella treatment in cats, consider 
follow-up testing to help assess response.
• CBC, platelet count, and liver enzymes—
monitor for side effects of systemic immuno-
suppressive drugs.
• Intraocular pressure monitoring—for 
anterior uveitis.
Tick and flea control measures.POSSIBLE COMPLICATIONS
• Permanent blindness.
• Cataracts.
• Chronic ocular pain.
• Death—secondary to systemic disease.
• Prognosis for vision—guarded to good, 
depending on amount of retina affected; 
visual deficits or blindness if large areas of the 
retina were destroyed; focal and multifocal 
disease do not markedly impair vision but do 
leave scars.
• Prognosis for life—guarded to good, depending 
on underlying cause.
• Prognosis for globe—secondary glaucoma 
may necessitate removal of blind painful eye.
Several systemic diseases.
• Toxoplasmosis—may be transmitted to 
humans if patient is shedding oocysts in feces.
• Vector-borne diseases—infected animals 
may act as reservoirs, i.e., bartonella (cat 
scratch disease), rickettsia, others.
SYNONYMS
Retinochoroiditis
SEE ALSO
• Retinal Degeneration.
• Retinal Detachment.
• Uveodermatologic Syndrome (VKH).
Narfström K, Petersen-Jones S. Diseases of 
the canine ocular fundus. In: Gelatt KN, 
Ames, IA: Blackwell, 2013, pp. 2087–2235.
Stiles J. Infectious diseases and the eye. Vet 
Clin North Am Small Anim Pract 2000, 
30:971–1167.
Author  Patricia J. Smith

274  Blackwell’s Five-Minute Veterinary Consult  
CChronic Kidney Disease
 BASICS
Chronic kidney disease (CKD) encompasses 
functional or structural lesions (in one or 
both kidneys as detected by blood or urine 
tests, imaging studies, or kidney biopsy) 
that have been present for >3 months. This 
definition includes all cases previously 
described by the terms renal insufficiency 
or renal failure, as well as less advanced 
forms of kidney disease. Patients are 
categorized into stages along a continuum 
of progressive CKD (IRIS CKD stages 1–4; 
www.iris-kidney.com) based on >2 serum 
creatinine values obtained over several 
weeks when the patient is fasted and well 
hydrated. The IRIS system uses the term 
“kidney” rather than “renal” because it is 
more universally recognized by pet owners.
More than ~67–75% reduction in renal 
function results in impaired urine-
concentrating ability (leading to polyuria/
polydipsia [PU/PD]) and retention of 
nitrogenous waste products of protein 
catabolism (azotemia). CKD is progressive; 
more advanced CKD results in uremia. 
Decreased renal erythropoietin and calcitriol 
production results in hypoproliferative 
anemia and renal secondary hyperpara -
thyroidism, respectively.
• Cardiovascular—hypertension; uremic 
pericarditis.
hyperparathyroidism, activation of renin-
angiotensin-aldosterone system, erythropoietin 
• Gastrointestinal—uremic stomatitis and 
halitosis, nausea, vomiting, anorexia, 
gastrointestinal bleeding, diarrhea.
• Hemic/lymphatic/immune—anemia; 
hemorrhagic diathesis.
• Musculoskeletal—renal osteodystrophy; 
sarcopenia.
• Neuromuscular—seizures and other 
neurologic signs, muscle tremors, muscle 
wasting.
• Ophthalmic—retinal detachment, 
hemorrhage, or edema due to hypertension.
• Reproductive—impaired reproductive 
capacity.
• Respiratory—uremic pneumonitis.
GENETICS
• Inherited in these breeds (mode of 
inheritance indicated in parentheses)—
Abyssinian cat (dominant with incomplete 
penetrance); Persian cat (dominant); bull 
terrier (dominant); Cairn terrier (recessive); 
German shepherd (dominant); Samoyed (X-linked dominant); English cocker spaniel 
(recessive).
• Renal dysplasia—shih tzu, Lhasa apso, 
golden retriever, Norwegian elkhound, chow 
chow, standard poodle, soft-coated wheaten 
terrier, Alaskan Malamute, miniature 
schnauzer, Dutch kooiker, and many other 
breeds.
• 9 cases per 1,000 dogs and 16 cases per 
1,000 cats examined.
• Prevalence increases with age—age >15 
years, reportedly 57 cases per 1,000 dogs and 
153 cases per 1,000 cats examined.
Worldwide
Species
See Genetics.
Mean age at diagnosis is 7 years in dogs and 9 
years in cats. Animals of any age can be 
affected; prevalence increases with age.
None
SIGNS
• Clinical signs related to stage of CKD and 
complications such as proteinuria and hyper  - 
tension.
• CKD stages 1 and 2 may be asymptomatic; 
overt clinical signs typically become apparent 
in stages 3 and 4.
• Animals with stable CKD (particularly 
stages 3 and 4) may decompensate, resulting 
in uremic crisis.
• PU/PD.
• Nocturia.
• Acute blindness.
• Seizures or coma.
• Cats may have ptyalism and muscle 
weakness with cervical ventroflexion.
• Kidneys may be small, irregular, enlarged 
(secondary to polycystic kidney disease or 
lymphoma), or normal.
• Cachexia.
• Mucous membrane pallor.
• Oral ulceration.• Uremic halitosis.
• Hypertensive retinopathy.
• Renal osteodystrophy may manifest as bone 
pain, particularly in skull.
• Reduced body temperature with uremia.
CAUSES
• Unknown in most cases due to late 
• Familial and congenital renal disease, 
nephrotoxins, hypercalcemia, hypokalemic 
nephropathy, glomerulopathies, amyloidosis, 
pyelonephritis, polycystic kidney disease, 
nephroliths, chronic urinary obstruction, 
drugs, lymphoma, leptospirosis (following 
acute kidney injury [AKI]), feline infectious 
Age, proteinuria, hypercalcemia, hypokalemia, 
hypertension, urinary tract infection (UTI).
 DIAGNOSIS
• See Polyuria and Polydipsia for differential 
• Azotemia—includes causes of prerenal and 
postrenal azotemia, AKI, and hypoadreno  - 
• Prerenal azotemia—azotemia with urine 
specific gravity (USG) >1.030 in dogs and 
>1.035 in cats; rapid reduction in azotemia 
after correcting hypoperfusion indicates 
prerenal azotemia; prerenal azotemia 
commonly occurs concurrent with primary 
renal azotemia when gastrointestinal signs of 
uremia are present.
• Postrenal azotemia—obstruction or rupture 
of excretory system; rapid correction of 
azotemia following elimination of obstruction 
or resolution of leakage from urinary tract 
supports postrenal azotemia.
• AKI—differentiated by normal to large 
renal size, cylindruria, lack of indications of 
chronicity, and history of recent nephrotoxin 
exposure or hypotensive episode; AKI can 
also occur in patients with CKD where rapid 
developing increase in serum creatinine 
concentration and uremic signs suggests 
acute-onset CKD.
• Hypoadrenocorticism—characterized by 
hyponatremia and hyperkalemia with hypo  - 
cortisolemia.
• Hypoproliferative anemia.
• High blood urea nitrogen (BUN), creatinine, 
and symmetric dimethylarginine (SDMA).
• Metabolic acidosis (normal or high anion 
gap).
• Hypokalemia or hyperkalemia.
• Hypercalcemia or hypocalcemia.

Canine and Feline, Seventh Edition  275
C(continued)  Chronic Kidney Disease
• USG <1.030 in dogs and <1.035 in cats.
Urinary protein : creatinine ratio to assess 
IMAGING
• Abdominal radiographs may demonstrate 
small kidneys, or large kidneys secondary to 
polycystic kidney disease or lymphoma.
• Ultrasound demonstrates small kidneys and 
hyperechoic renal parenchyma with less 
apparent distinction between cortex and 
medulla in some animals. Animals with 
lymphoma often have renomegaly with 
hypoechoic renal parenchyma.
• Blood pressure measurement to detect 
• Measurement of glomerular filtration rate 
may be useful for detection of loss of kidney 
function before onset of azotemia.
• Renal biopsy may be indicated in proteinuric 
patients with normal to large kidneys.
• Gross—small kidneys with irregular 
surface; fewer glomeruli found on visualizing 
cut across renal cortex.
• Histopathologic—variable; complete 
evaluation of biopsy material requires light, 
immunofluorescent, and electron microscopy; 
advanced CKD has nonspecific changes 
including interstitial fibrosis and foci of 
interstitial mononuclear cells, chronic 
generalized nephropathy.
• Findings may be specific for diseases 
causing CKD in some patients with less 
 TREATMENT
Patients with compensated CKD may be 
managed as outpatients; patients in uremic 
crisis should be managed as inpatients.
• Uremic crisis—correct fluid and electrolyte 
deficits with IV fluids, providing 25% of 
calculated fluid deficit in first hour; thereafter, 
serially monitor perfusion, blood pressure, and 
urine output to assess adequacy of fluid therapy; 
if perfusion not improved, additional fluid 
should cautiously be administered. Provide 
remaining fluid deficit over next 12–24 hours. 
Overhydration can result in anuria; once 
patient has been hydrated, only sufficient fluid 
to sustain hydration should be administered.
• Subcutaneous fluid therapy may benefit 
patients with moderate to severe CKD. Continue 
therapy only if clinical improvement noted.
ACTIVITY
UnrestrictedDIET
• Diets designed for CKD delay onset of 
uremic crisis and extend survival in dogs and 
cats with CKD stages 2–4; they are standard 
of care for these patients.
• Important components of renal foods—
reduced protein, phosphorus, sodium, and 
net acid content, supplementation of n-3 
fatty acids and antioxidants.
• Free access to fresh water.
• CKD typically progresses to terminal kidney 
failure over months to years, but may not be 
progressive in some cats, which may live for years
• Higher levels of proteinuria associated with 
shorter survival; may be mitigated by anti  - 
proteinuria therapy.
• Heritability of familial renal diseases.
• Avoid hypotension during anesthesia.
• Renal transplantation has been successfully 
performed in cats with CKD.
Uremic Crisis
• Antiemetics (maropitant 1 mg/kg q24h; or 
ondansetron 0.2–1 mg/kg IV q12h) to minimize 
vomiting and hyporexia due to nausea.
• Potassium chloride in IV fluids or 
potassium gluconate PO (2–6 mEq/cat/day) 
as needed to correct hypokalemia.
• Sodium bicarbonate to correct metabolic 
acidosis (IV to raise blood pH >7.1).
Compensated CKD
• Antiemetic (maropitant) and potassium 
gluconate as above.
• Mirtazapine (cats, 1.88 mg PO q 24–47h) 
to promote appetite.
• Intestinal phosphate binders as needed to 
correct hyperphosphatemia (see 
Hyperparathyroidism, Renal Secondary).
• Darbepoetin (see Anemia of Chronic 
Kidney Disease).
• Amlodipine (dogs, 0.1–0.6 mg/kg PO q24h; 
cats, 0.625–1.25 mg/cat PO q24h) or 
inhibitors (0.5 mg/kg PO q24h) or angiotensin 
receptor blockers (ARB; e.g., telmisartan 
1–3 mg/kg PO q24h) as needed for hyperten -
sion; amlodipine and telmisartan are more 
effective than ACE inhibitors for CKD-induced 
hypertension; if refractory to monotherapy, 
consider combination of amlodipine and ACE 
inhibitor or ARB, with frequent monitoring of 
blood pressure and electrolytes.
• ACE inhibitor (start at 0.5 mg/kg PO 
q24h; increase to 1 mg/kg PO q12h) or ARB 
(telmisartan 1–3 mg/kg PO q24h) for 
proteinuria.CONTRAINDICATIONS
Avoid nephrotoxic drugs (aminoglycosides, 
cisplatin, amphotericin B) and corticosteroids.
• Drug dosage or dosing interval may need to 
be modified for some drugs eliminated by the 
kidneys.
• Use ACE inhibitors and ARB cautiously; 
monitor for worsening of azotemia,
• Generally avoid nonsteroidal anti-inflam-
matory drugs.
Cimetidine or trimethoprim may cause 
artifactual increases in serum creatinine 
concentration by reducing tubular secretion 
in dogs with CKD.
• Metoclopramide (0.2–0.4 mg PO/SC 
q6–8h) can be used to treat uremic vomiting.
• Hemodialysis and renal transplantation are 
available at selected referral hospitals.
 FOLLOW-UP
• Monitor at regular intervals; initially weekly 
for patients receiving erythropoietin; every 
1–3 months for stable patients with CKD 
stages 3 and 4.
• Proteinuric patients—monitor at least every 
3–4 months (minimum: serum creatinine and 
urine protein : creatine ratio).
• Do not breed animals with familial renal 
disease.
• Include urinalysis and serum creatinine in 
yearly examination for older pets; if serum 
creatinine increases, increase frequency to 
every 4–6 months.
• Uremia.
• Anemia.
• UTI.
• Nephrouretrolithiasis.
• Short term—depends on severity.
• Long term—guarded to poor in dogs (CKD 
tends to be progressive over months to years); 
poor to good in cats (CKD does not progress 
in some cats).
• Renal secondary hyperparathyroidism.
• Nephroureterolithiasis.

276  Blackwell’s Five-Minute Veterinary Consult  
CChronic Kidney Disease  (continued)
Renal function may decrease with aging.
None
Patients with mild CKD may maintain 
pregnancy; those with moderate to severe 
disease may be infertile or have spontaneous 
abortions; breeding of females not recomm  - 
ended.
SYNONYMS
• Chronic kidney failure.
• Chronic renal disease or failure.
SEE ALSO
• Anemia of Chronic Kidney Disease.
• Congenital and Developmental Renal 
Diseases.• Hydronephrosis.
• Hyperparathyroidism, Renal Secondary.
• Nephrolithiasis.
• Polycystic Kidney Disease.
• Polyuria and Polydipsia.
• ARB = angiotensin receptor blocker.
• SDMA = symmetric dimethylarginine.
• UTI = urinary tract infection.INTERNET RESOURCES
www.iris-kidney.com
Polzin DJ. Chronic kidney disease. In: 
Ettinger SJ, Feldman EC, eds., Textbook of 
Veterinary Internal Medicine, 7th ed.  
St. Louis, MO: Elsevier, 2010, pp. 1990–2021.
Ross SJ, Polzin DJ, Osborne CA. Clinical 
progression of early chronic renal failure 
and implications for management. In: 
August JR, ed., Consultations in Feline 
Internal Medicine. St. Louis, MO: Elsevier, 
2006, pp. 389–398.

Canine and Feline, Seventh Edition  277
C
 BASICS
• Accumulation of chyle in the pleural space. 
• Chyle—triglyceride-rich fluid from the 
intestinal lymphatics that empties into the 
venous system (usually cranial cava/jugular 
vein) in the thorax. •  Pseudochylous 
effusion—effusion that contains less triglycer -
ides and more cholesterol compared to serum, 
but appears fatty grossly. •  Thoracic lymphan -
giectasia—tortuous, dilated lymphatics found 
in many animals with chylothorax. •  Fibrosing 
pleuritis—condition in which pleural thick  - 
ening leads to constriction of lung lobes; when 
severe, results in marked restriction of 
ventilation; can be caused by any chronic 
pleural exudate, but is most commonly 
associated with chylothorax and pyothorax.
• Alteration of flow through thoracic duct (TD) 
leading to leakage of chyle—can be related to 
increased pressure or permeability in TD or 
venous obstruction downstream. •  Can be 
caused by any disease or process that increases 
systemic venous pressure at the entrance of the 
TD to the venous system. •  Cardiac causes—
pericardial disease, cardiomyopathy, heartworm 
disease, other causes of right-sided heart failure; 
thrombosis around pacing lead wire. 
• Noncardiac causes—neoplasia (especially 
mediastinal lymphoma in cats), lung lobe torsion, 
diaphragmatic hernia, venous granuloma, venous 
thrombus. •  Rare TD rupture/trauma—surgical 
(thoracotomy), nonsurgical (e.g., hit by car). 
• Idiopathic considered most common.
• Respiratory—due to reduced lung 
expansion. •  Systemic signs can be present 
secondary to the respiratory distress  
(e.g., decreased appetite, weight loss).
GENETICS
Unknown
Unknown
Worldwide
Species
• Dogs—Afghan hound and Shiba Inu. 
• Cats—oriental breeds (e.g., Siamese and 
Himalayan).
• Any age affected. •  Cats—more common 
in older cats; could indicate an association 
with neoplasia. •  Afghan hound—develop when middle-aged. •  Shiba Inu—develop 
when young (<1–2 years of age).
SIGNS
• Signs will depend on the rate of fluid 
accumulation and volume of pleural effusion. 
• Usually not exhibited until there is marked 
impairment of ventilation. •  Many patients 
appear to have the condition for prolonged 
periods before diagnosis.
• Tachypnea and respiratory difficulty. 
• Coughing—can be present for months 
before examination, likely due to lung 
compression associated with pleural effusion. 
• Lethargy. •  Anorexia and weight loss. 
• Vary with cause of effusion. •  Muffled heart 
and lung sounds ventrally. •  Increased 
bronchovesicular sounds, particularly in dorsal 
lung fields. •  Pale mucous membranes or 
cyanosis. •  Arrhythmia. •  Heart murmur. 
• Signs of right-sided heart failure (e.g., jugular 
pulses, ascites, hepatomegaly). •  Decreased 
compressibility of anterior chest—common in 
cats with a cranial mediastinal mass.
CAUSES
• Cranial mediastinal masses—lymphoma, 
thymoma. •  Cardiac disease—heartworm, 
cardiomyopathy, pericardial disease, congenital 
diseases. •  Lung lobe torsion. •  Venous 
obstruction—granuloma, thrombi. •  Congenital 
abnormality of TD. •  Cardiac or thoracic 
surgery. •  Idiopathic—most common cause.
Unknown
 DIAGNOSIS
Other causes of pleural effusion—neoplasia, 
pyothorax, heart failure, feline infectious 
peritonitis (FIP).
• Often normal. •  Lymphopenia and 
hypoalbuminemia—can be found; hypona-
tremia and hyperkalemia sometimes noted 
due to fluid shifts with repeat thoracocentesis.
Heartworm testing.
Fluid Analysis
• Classified as an exudate. •  Color will depend 
on fat content from diet and presence of 
concurrent hemorrhage—usually milky white 
and opaque, but can appear serosanguinous and range from yellow to pink. •  Protein 
content varies, and high lipid content will 
make refractive index inaccurate. •  Total 
nucleated cell count—usually <10,000 
cells/μL. • Fluid triglycerides—higher 
compared to serum. •  Fluid cholesterol—
lower compared to serum.
Cytology
• Place sample in an EDTA tube to allow cell 
count to be performed. •  Initially, cytology 
comprises primarily small lymphocytes, 
neutrophils, and macrophages containing 
lipid. •  Chronic effusions contain fewer 
lymphocytes due to continued loss and more 
nondegenerate neutrophils due to inflamma-
tion from multiple thoracocenteses or 
irritation of pleural lining by chyle. •  Atypical 
lymphocytes—suggestive of underlying 
IMAGING
• T wo to four views if patient is stable—  
pleural effusion. •  Dorsoventral view 
associated with less stress than ventrodorsal 
view in animal with respiratory difficulty. 
• Repeat radiographs after thoracocentesis to 
assess for underlying causes of effusion or 
evidence of fibrosing pleuritis; if collapsed lung 
lobes do not appear to reexpand after pleural 
fluid is removed or if respiratory distress 
persists with only minimal fluid present, 
suspect underlying pulmonary parenchymal or 
pleural disease (e.g., fibrosing pleuritis).
Ultrasonography/Echocardiography
• Should be performed before thoracocentesis 
if patient is stable—fluid acts as an acoustic 
window, enhancing visualization of thoracic 
structures. •  Assess for underlying causes—
detect abnormal cardiac structure and function, 
pericardial disease, and mediastinal masses.
CT Lymphangiography
• Can quantify TD branches more accurately 
than standard radiographic lymphangiogra-
phy. •  In dogs, percutaneously inject 1–2 mL 
of nonionic contrast material into mesenteric 
lymph nodes using ultrasound or CT 
guidance. •  Acquire helical thoracic CT 
images before and after injection of contrast 
media. •  Can document location and 
character of TD and its tributary lymphatics; 
likely useful for surgical planning.
• Lymphatics (including TD)—difficult to 
identify at necropsy. •  Fibrosing pleuritis—
lungs appear shrunken; pleural layers (visceral 
and parietal) are diffusely thickened. 
• Fibrosing pleuritis—characterized 
histologically by diffuse, moderate to marked 
thickening of the pleura by fibrous connective 
tissue with moderate infiltrates of lympho-
cytes, macrophages, and plasma cells.Chylothorax

278  Blackwell’s Five-Minute Veterinary Consult  
CChylothorax  (continued)
 TREATMENT
• Dyspneic animal—immediate thoraco -
centesis; removal of even small amounts of 
pleural effusion can markedly improve 
ventilation. •  Identify and treat the 
underlying cause, if possible. •  Medical 
management—usually treated on outpatient 
basis with intermittent thoracocentesis as 
needed based on clinical signs (see Medications). 
• Chest tubes—place only in patients with 
suspected chylothorax secondary to trauma 
(very rare), in cases with rapid fluid 
accumulation, or after surgery. •  Surgery if 
medical management does not resolve the 
problem in 2–3 months (see Surgical 
Considerations); some clinicians believe 
earlier intervention is better to avoid potential 
for development of restrictive pleuritis.
• Patients undergoing multiple thoraco -
centeses can rarely develop electrolyte 
abnormalities (hyponatremia, hyperkalemia) 
that may need to be corrected with fluid 
therapy. •  Thoracocentesis—perform under 
aseptic conditions to reduce risk of 
iatrogenic infection; antibiotic prophylaxis 
generally unnecessary if proper technique is 
used.
ACTIVITY
Patients will usually restrict their own exercise 
as pleural fluid volume increases or if they 
develop fibrosing pleuritis.
DIET
• Low fat—potentially decreases the amount 
of fat in the effusion, which would improve 
the patient’s ability to resorb fluid from the 
thoracic cavity; not a cure; may help in 
management by facilitating reabsorption. 
• Medium-chain triglycerides are transported 
via the TD in dogs and are no longer 
• Inform client that no specific treatment will 
stop the effusion in all patients with the 
idiopathic form of the disease. •  Inform 
client that the condition can spontaneously 
resolve in some patients after several weeks or 
months.
TD Ligation and Pericardiectomy
• Recommended in patients that do not 
respond to medical management. •  The 
duct usually has multiple branches in the 
caudal thorax where ligation is performed; 
failure to occlude all branches results in 
continued pleural effusion. •  Always perform in conjunction with lymphangiog -
raphy; methylene blue injected in the 
mesenteric lymph node greatly facilitates 
visualization and complete occlusion of all 
branches. •  Thickening of the pericardium 
can prevent formation of lymphaticovenous 
communications—perform pericardiectomy 
simultaneously with TD ligation; reports of 
up to 100% success rate when both 
techniques are performed; second surgery 
can be necessary if all branches are not 
occluded. •  Video-assisted thorascopic 
surgery for thoracic duct ligation and 
pericardiectomy is reported to have similar 
success rates to thoracotomy (86%).
Other
• Success rates of 83–88% reported for 
cysterna chyli ablation in combination with 
TD ligation. •  Salvage procedures for 
recurrence after TD ligation include cisterna 
chyli and TD glue embolization, pleuroperi-
toneal or pleurovenous shunts, or placement 
of a PleuralPort ®.
• Rutin 50–100 mg/kg PO q8h; believed to 
increase macrophage removal of proteins, 
which promotes absorption of fluid; complete 
resolution of effusion appears to occur in 
some patients; further study is required to 
determine whether resolution occurs 
spontaneously or in response to this therapy. 
• Somatostatin analog (octreotide)—a 
naturally occurring substance that inhibits 
gastric, pancreatic, and biliary secretions and 
prolongs gastrointestinal transit time, 
decreases jejunal secretion, and stimulates 
gastrointestinal water absorption; in traumatic 
chylothorax, reduction of gastrointestinal 
secretions may aid healing of the TD by 
decreasing TD lymphatic flows; resolution of 
pleural fluid has occurred in dogs and cats 
with idiopathic chylothorax in which 
octreotide has been administered, but the 
mechanism is unknown; octreotide 
(Sandostatin®; 10  μg/kg SC q8h for 2–3 
weeks) is a synthetic analog of somatostatin 
that has a prolonged half-life and minimal 
side effects.
Cardiac disease or neoplasia—treat the 
underlying disease rather than the effusion 
(other than heartworm disease in cats where 
TD ligation may be beneficial while the 
heartworm infection clears). FOLLOW-UP
• Monitor for signs of recurrence of pleural 
effusion (tachypnea, labored breathing, 
respiratory distress)—perform thoracentesis 
as needed. •  Periodically reevaluate for several 
years to detect recurrence.
• Fibrosing pleuritis. •  Iatrogenic infection 
with repeated thoracocentesis—important to 
use aseptic technique.
• Can resolve spontaneously or after surgery. 
• Untreated or chronic disease—can result in 
severe fibrosing pleuritis and persistent dyspnea. 
• Euthanasia—frequently performed in 
patients that do not respond to surgery or 
Diffuse lymphatic abnormalities (e.g., intestinal 
lymphangiectasia, hepatic lymphangiectasia, 
pulmonary lymphangiectasia, and chylous ascites)—  
may be noted; may worsen the prognosis.
Young patients may have a better prognosis 
than old animals because of the association of 
neoplasia with advanced age.
• TD = thoracic duct.
Allman DA, Radlinsky MG, Ralph AG, 
Rawlings CA. Thoracoscopic thoracic duct 
ligation and thoracoscopic pericardiectomy 
for treatment of chylothorax in dogs. Vet Surg 
2010, 39(1):21–27.
Fossum TW, Mertens MM, Miller MW, et al. 
Thoracic duct ligation and pericardectomy 
for treatment of idiopathic chylothorax. 
J Vet Intern Med 2004, 18:307–310.
Johnson EG, Wisner ER, Kyles A, et al. 
Computed tomographic lymphography of 
the thoracic duct by mesenteric lymph node 
injection. Vet Surg 2009, 38(3):361–367.
Author  Elizabeth Rozanski
Jill S. Pomrantz.

Canine and Feline, Seventh Edition  279
CCirrhosis and Fibrosis of the Liver
 BASICS
• Hepatic fibrosis—replacement/effacement 
of hepatic parenchyma, intrasinusoidal, 
variable zonal, deposition of extracellular 
matrix (ECM). 
• Cirrhosis—regenerative nodules with 
dissecting fibrotic partitions and regions of 
parenchymal extinction, deranging hepatic 
architecture; usually reflects chronic necro  - 
inflammatory liver injury.
• Fibrosis—usually reflects injury-associated 
release of cytokines/mediators stimulating 
production and accumulation of ECM; 
exception: ductal plate malformation (DPM), 
with congenital hepatic fibrosis (CHF) 
phenotype (severe portal-to-portal bridging 
fibrosis without chronic inflammation). 
• Cirrhosis—consequence of chronic hepatic 
injury, fibrogenesis, and hepatic regeneration; 
typified by regenerative nodules, reduced 
functional hepatic mass, collagen deposition 
in sinusoids (space of Disse) or portal tracts, 
compromising parenchymal perfusion.  
• Cirrhosis/fibrosis—leads to hepatic dysfun- 
ction, capillarization of hepatic sinusoids, 
collagenization of sinusoids, development of 
sinusoidal hypertension, intrahepatic 
shunting through collagenized sinusoids, 
recanalized vascular pathways in fibrotic 
partitions between regenerative nodules; these 
microcirculatory disturbances impair 
exchanges between blood and hepatocytes. 
• Sinusoidal hypertension—leads to 
hepatofugal portal flow (away from liver); 
splanchnic hypertension; acquired portosys -
temic shunt (APSS) formation; episodic 
hepatic encephalopathy (HE); splanchnic 
pooling of blood, decreased effective systemic 
blood volume, stimulation of renal sodium 
and water retention, with ascites formation; 
hypertensive splanchnic vasculopathy 
predisposing to enteric bleeding.
• Gastrointestinal (GI)—splanchnic portal 
hypertension leads to ascites and propensity 
for enteric bleeding. 
• Neurologic—HE.  
• Hemic—red blood cell (RBC) microcyto -
sis reflects APSS; bleeding tendencies: failed 
factor synthesis or activation, thrombocyto -
penia; reduced anticoagulants increases risk 
for thrombosis. 
• Renal/urologic—ammonium biurate 
crystalluria; isosthenuria: polyuria/
polydipsia (PU/PD); hepatorenal syndrome 
(rare) may follow therapeutic paracentesis of 
large-volume ascites (postcentesis hypoten -
sion syndrome [PHS]). 
• Endocrine/metabolic—hypoglycemia if 
end-stage liver failure. • Respiratory—tachypnea if tense ascites or 
pleural effusion. 
• Skin—superficial necrolytic dermatitis, 
unkempt coat.
GENETICS
Familial predisposition for chronic hepatitis—  
Doberman pinscher, cocker spaniel, Labrador 
retriever, Maltese, Bedlington terrier (copper 
related), West Highland white terrier, others.
High in dogs with chronic necroinflammatory 
liver disease, animals with chronic extrahepatic 
bile duct occlusion (EHBDO), dogs with 
severe hepatic copper accumulation.
Species
• Cirrhosis—dogs with chronic hepatitis; cats 
with chronic cholangitis/cholangiohepatitis; 
dogs and cats with chronic EHBDO.
•  Severe fibrosis—dogs and cats with severe 
DPM-CHF phenotype.
• Many breeds and mixed-breed dogs. 
• Copper associated hepatopathy (CuAH)—
genetics proven only in Bedlington terriers and 
partially in Labrador retrievers; Doberman 
pinschers, West Highland white terriers, and 
Dalmatians appear predisposed; but all breeds at 
risk for CuAH due to dietary Cu intake. 
• DPM-CHF phenotype—boxers may  
be predisposed, many breeds of dogs and  
cats; cats with polycystic malformations at 
risk.
• Cirrhosis (dogs)—any age; more common 
in middle-aged to older; CuAH any age. 
• Biliary cirrhosis (cats)—with chronic 
cholangiohepatitis often >7 years old. 
• Fibrosis—DPM-CHF phenotype (dogs, 
cats)—ECM accumulates with aging 
(suspected), genetic cause (see Ductal Plate 
Malformation).
Predominant Gender
• Cocker spaniels—may be higher in  
males. 
• Doberman pinschers and Labrador 
retrievers—no sex predilection. 
• DPM—no gender predilection.
SIGNS
• Initially—vague and nonspecific. 
• Later—relate to complications of portal 
hypertension (e.g., HE, ascites, gastroduo -
denal bleeding) and impaired hepatic 
function.
• Chronic intermittent lethargy, anorexia, 
reduced body condition. 
• GI signs—vomiting, diarrhea or constipa-
tion. Melena—late stage or as APSS develop. 
• PU/PD. 
• Late onset—ascites, bleeding, HE.•  Jaundice—with necroinflammatory 
disease; DPM usually anicteric. 
• Cats—ascites uncommon with acquired 
necroinflammatory disease, more common with 
DPM; ptyalism, aggression, seizures with HE.
• Lethargy. 
• Poor body condition/coat. 
• ± Variable jaundice. 
• ± Ascites. 
• ± HE. 
• Obstructive uropathy—ammonium 
biurates. 
• Anasarca—rare; may develop with over  - 
zealous fluid therapy. 
• Liver size—dogs: microhepatia; cats: variable. 
• Coagulopathy—variable, uncommon in DPM. 
• Cutaneous lesions—superficial necrolytic 
dermatitis.
CAUSES
• Chronic necroinflammatory, oxidant, or 
immune-mediated liver injury has many causes; 
may develop subsequent to chronic inflamma -
tory bowel disease (IBD) or pancreatitis. 
• CuAH. 
• Drug- or toxin-induced liver injury—anti-
convulsants; azole antifungals; nonsteroidal 
anti-inflammatory drug (NSAID) oxibenda-
zole; trimethoprimsulfamethoxazole; chronic 
food-borne toxins (aflatoxins), others. 
• Infections—leptospirosis, canine adenovirus 
I, leishmanial, histoplasmosis, protozoal 
(toxoplasmosis). 
• Chronic cholangiohepatitis (cats). 
• Chronic EHBDO (>6 weeks, dogs and cats). 
• Single episode of massive hepatic necrosis; 
sago palm (cycad toxicity), xylitol, NSAIDs 
in dogs with substantial Cu accumulation.
• Breed predisposition. 
• Dietary Cu intake >patient tolerance. 
• Hepatic iron accumulation— 
supplementation. 
• Chronic hepatobiliary inflammation. 
• Chronic EHBDO. 
• Chronic phenobarbital administration (dogs). 
• NSAIDS—dogs, especially carprofen.
 DIAGNOSIS
• Chronic hepatitis—common in dogs. 
• Cholangiohepatitis—common in cats.  
• Noncirrhotic portal hypertension—dogs.  
• Chronic EHBDO.  
• Chronic IBD or pancreatitis.  
• Hepatic neoplasia.  
• Metastatic neoplasia or carcinomatosis.  
• Congenital portosystemic vascular anomaly 
(shunt).  
• Congenital portal atresia—intrahepatic or 
extrahepatic.  
• Right-sided heart failure, pericardial disease.

280  Blackwell’s Five-Minute Veterinary Consult  
CCirrhosis and Fibrosis of the Liver  (continued)
• Cats—hepatic lipidosis, feline infectious 
peritonitis, toxoplasmosis.  
• Hemolytic anemia (jaundice differential).
CBC
• Microcytic RBCs: APSS; mild anemia: 
small RBCs with normal cell count; anemia 
of chronic disease; microangiopathic shearing: 
sinusoidal fibrosis, APSS.  
• Mild thrombocytopenia variable.  
• Leukogram variable.
• Bilirubin variable.  
• Liver enzyme activities—high (alanine 
transaminase [ALT] > alkaline phosphatase 
[ALP]) noted before clinical signs or liver 
dysfunction; at end-stage enzymes may decline.  
• Normal to hypoalbuminemia.  
• Normal to hyperglobulinemia.  
• Hypocholesterolemia—reflects APSS.  
• Low blood urea nitrogen (BUN)—reduced 
urea cycle activity, APSS, protein-restricted 
diet, PU/PD.  
• Hypoglycemia—rare.  
• Hypokalemia—may predispose to HE.  
• Hyponatremia—fluid imbalance with 
ascites.
• Isosthenuria—with PU/PD.  
• Ammonium biurate crystalluria.  
• Bilirubinuria, bilirubin crystalluria.
• Ascitic fluid—pure or modified transudate.  
• Coagulation tests—inconsistently prolonged 
prothrombin time (PT), activated partial 
thromboplastin time, buccal mucosal 
bleeding time (BMBT).  
• Low protein C and antithrombin activity—
reflects APSS, synthetic failure, or dissemi-
nated intravascular coagulation (DIC).  
• Serum bile acids—high; reflects APSS or 
cholestasis in cirrhosis.  
• Hyperammonemia—inferred from 
ammonium biurate crystalluria.
IMAGING
Abdominal—small to normal-sized liver; 
ascites may obscure details; urate calculi 
radiolucent unless calcium complexed.
• Abdominal—hyperechoic or mixed 
echogenic liver parenchyma; ± nodularity; 
often small with cirrhosis; abdominal effusion 
(ascites); APSS (color-flow Doppler); enlarged 
portal lymph nodes; no parenchymal change 
in some cases.  
• Doppler interrogation of portal vasculature—
may confirm hepatofugal flow or nests of APSS, 
esp. near left kidney or splenic vessels.
• Fine-needle aspiration cytology—helps rule 
out neoplasia; rule in bacterial infection; 
cannot define fibrosis  or nonsuppurative 
inflammation.  • Liver biopsy—for definitive diagnosis; 
accuracy increased by multiple biopsy samples.  
• Ultrasound guided—14–16G.  
• Laparoscopy/laparotomy—best methods, 
permits gross visualization, documents APSS, 
biopsy access to multiple liver lobes and focal 
lesions.
Gross
• Fibrosis—small, firm irregular to finely 
nodular liver; DPM-CHF may not be small; 
fibrotic liver may display APSS, ± ascites.  
• Cirrhosis—firm irregular liver; prominent 
micro- or macronodules, APSS, ± ascites.
• Immune-mediated hepatitis—periportal, 
lobular, or centrilobular lymphoplasmacytic 
infiltrates, hepatic cord disorganization, 
sinusoidal fibrosis, biliary hyperplasia.
• CuAH—initially centrilobular, may evolve 
immune-mediated hepatitis; single necrotic 
hepatocytes; significant fibrotic tissue may 
falsely decrease quantitative Cu concentration 
measurements in biopsy samples.  
• DPM—bridging partitions with proliferative 
nonfunctional embryonic bile ducts embedded 
in ECM interconnecting portal regions.
• Postnecrotic fibrosis—fibrosis marks regen  - 
erative repair, disorganized wide hepatic 
cords; engorged lymphatics reflect sinusoidal 
hypertension.  
• Cirrhosis—diffuse lesion; fibrosis, nodular 
regeneration distorting lobular architecture, 
periportal or sinusoidal fibrosis depending on 
zone of chronic injury, engorged lymphatics; 
single hepatocyte necrosis if active disease.
 TREATMENT
• Outpatient—minimally symptomatic 
patients.  
• Inpatient—diagnostic tests; treatment for 
dehydration, severe HE, enteric bleeding, 
tense ascites.
• Fluids—avoid lactate if hepatic failure; 
avoid sodium loading if ascites.  
• B complex vitamins (esp. cats)—2 mL/L 
fluid advised.  
• Vitamin K1—0.5–1.5 mg/kg SC q12h for 3 
doses initially; titrate with proteins invoked 
by vitamin K absence or antagonism (PIVKA; 
if available) or PT.  
• Glucose—if hypoglycemia; 2.5–5% dextrose 
in polyionic solution; titrate to response.  
• Potassium chloride—in fluids, as needed.  
• Avoid alkalosis—worsens HE.  
• Therapeutic large-volume abdominocente-
sis if tense ascites nonresponsive to medical 
treatment; caution : PHS—hypotensive crisis 
and acute renal failure.ACTIVITY
Limit
DIET
• Withhold oral food in acute severe HE if 
stupor, coma, or vomiting associated with 
enteric bleeding or pancreatitis.  
• Consider partial parenteral nutrition or 
total parenteral nutrition.  
• If HE—restrict protein intake, use soy or 
dairy protein sources (dogs) with medical 
interventions to increase nitrogen tolerance 
(see Hepatic Encephalopathy).  
• Supplement water-soluble vitamins.
• T reatment palliative and symptomatic.  
• Fibrosis diminished by control of inflam-
mation and provocative diseases.  
• Attenuate factors provoking HE—
azotemia, dehydration; infection; catabolism; 
high-protein meals, hypokalemia; alkalemia; 
constipation, endoparasitism; enteric 
bleeding; certain drugs.
• Cirrhosis—high anesthetic risk; gas 
anesthesia preferred: isoflurane or 
sevoflurane.  
• Coagulopathy—predisposes to bleeding; 
BMBT may better assess risk for bleeding.  
• Postoperative intensive care—avoid HE, 
maintain hydration, euglycemia, electrolytes, 
acid-base balance (avoid alkalemia).  
• Predisposed to enteric bacterial transloca-
tion—judiciously administer antibiotics, esp. 
if surgical procedures involve alimentary canal 
or biliary structures.
• T reatments for specific etiologies—chelate 
Cu if CuAH; withdraw potentially hepatotoxic 
drugs, herbal or natural remedies.  
• No clinical trials prove efficacy of specific 
regimens in animals.
Immune Modulation
• Prednisolone /prednisone—1–2 mg/kg q24h 
PO; taper to 0.5 mg/kg q48h; do not exceed 
40 mg/day/dog.  
• Azathioprine—2 mg/kg (or 50 mg/m2) 
q24h for 14 days, then q48h; contraindicated 
in cats (toxic); dogs: with prednisone, anti  - 
oxidants, antifibrotics, and polyenylphos-
phatidylcholine (PPC).  
• Cyclosporine—5 mg/kg BID tapered to 
q24h; has been successful as single agent or 
with corticosteroids.  
• Mycophenolate—10–15 mg/kg BID; has 
been successful as first- or second-line treat  - 
ment with corticosteroids.
Antifibrotics
• Immunomodulation, S-adenosylmethionine 
(SAMe), silybin, vitamin E—considered 
antifibrotics as well as hepatoprotectants.

Canine and Feline, Seventh Edition  281
C(continued)  Cirrhosis and Fibrosis of the Liver
• Ursodiol—7.5 mg/kg/day PO q12h with 
food; use indefinitely.  
• Polyunsaturated phosphatidylcholine with 
dilinolylphosphatidylcholine (PhosChol®)— 
25 mg/kg/q24h, mix with food.  
• Colchicine—0.025–0.03 mg/kg q24–48h; 
no evidence of chronic benefit; side effects 
complicate use; no longer recommended.  
• Losartan and telmisartan—losartan: 0.5 mg/
kg/q24h; telmisartan: 0.5–1 mg/kg q24h 
initial dose; closely monitor blood pressure, 
renal function, and potassium, reducing dose 
if hypotension or hyperkalemia; angiotensin 
receptor blockers used in humans as antihy -
pertensives and have been shown to be 
nephroprotective, to protect against some 
forms of drug-induced hepatotoxicity, and to 
inconsistently limit hepatic fibrosis.
• Necroinflammatory disorders.  
• SAMe—20 mg/kg q24h PO, empty stomach .  
• Vitamin E mixed tocopherols—10 U/kg 
q24h PO with food.
Hepatoprotectants
• Ursodeoxycholate, vitamin E, SAMe.  
• Silibinin—efficacy unclear, use PPC 
complexed form (bioavailable), 2–5 mg/kg 
q24h PO.  
• Elemental zinc—1.5–3 mg PO q24h (if 
low liver zinc confirmed); adjust dose with 
plasma zinc measurements; avoid ≥800  μg/dL; 
contraindicated with concurrent d-penicil-
lamine administration.
Gastroprotectants
• Gastric acid inhibitors—if enteric bleeding 
(see Hepatitis, Chronic).  
• Eliminate endoparasitism.
Ascites
• Restrict activity and sodium intake 
combined with diuretic therapy.  
• Dietary sodium restriction (0.2% dry 
matter basis or <0.05 g/100 kcal).  
• Diuretics (see Hypertension, Portal; Hepatitis, 
Chronic); slowly mobilize effusion: furosemide 
(0.5–1 mg/kg IV/SC/PO q12h) with spironol -
actone (0.5–2 mg/kg PO q12h); adjust dose to 
response (7–10 day recheck; if no response 
titrate up q3–5d to max dose 4 mg/kg/day).  
• Therapeutic large-volume abdominocentesis 
if nonresponsive ascites mobilization after 
7–14 days of diuretics and sodium restriction.
• Consider vasopressin V2 antagonists with 
low-dose diuretics for treatment-resistant 
ascites (no published data for dogs or cats).
NSAIDs—avoid; potentiate enteric bleeding; 
may worsen ascites; potentiate centrilobular 
hepatic necrosis-hepatotoxic metabolites and 
CuAH.PRECAUTIONS
• Diuretics—dehydration, hypokalemia, 
alkalemia worsen HE.  
• Glucocorticoids—increase susceptibility 
to infection, enteric bleeding, sodium and 
water retention, ascites, protein catabolism, 
HE.  
• Avoid drugs or reduce dose if first-pass 
hepatic extraction, if require hepatic 
conjugation or biotransformation (e.g., 
metronidazole—reduce conventional dose to 
7.5 mg/kg PO q12h, as used for HE).
• Dexamethasone—if ascites, replace 
prednisone/prednisolone to avoid mineralo-
corticoid effect); divide dose by 7–10, 
administer q3–4 days; taper dose to efficacy.
 FOLLOW-UP
• Liver enzymes, albumin, BUN, cholesterol, 
bilirubin—monthly to quarterly.  
• Serial monitoring of total serum bile 
acids—adds no prognostic or diagnostic 
information.  
• Body condition score, weight, muscle 
mass—reflects nutritional adequacy/nitrogen 
balance.  
• Abdominal girth—reflects ascites volume.  
• Azathioprine, mycophenolate, colchicine—
monitor for bone marrow toxicity (serial 
CBCs) and other side effects.
HE, septicemia, bleeding—may be life-
threatening; DIC—may be terminal event.
• Flare-ups of HE and ascites may require 
hospitalization to adjust nutritional and 
medical interventions.  
• Sodium restriction and diuretics may 
require titration to achieve optimal control of 
ascites.  
• Presence of ascites indicates severe disease.  
• DPM—survival up to 12 years after diagnosis.
• Cirrhosis—variable: poor long-term prognosis 
in limited studies, <6 months; however, some 
can survive years (>5) with careful interventional 
management depending on whether histologic 
changes truly “end-stage” or not.
Dogs with leptospirosis-associated chronic 
liver disease (rare) may shed organisms.SEE ALSO
• Coagulopathy of Liver Disease.  
• Copper Associated Hepatopathy.  
Hepatic Fibrosis).  
• Hepatic Encephalopathy.  
• Hepatitis, Chronic.  
• ALP = alkaline phosphatase.  
• ALR = alanine transaminase.  
• APSS = acquired portosystemic shunt.  
• BMBT = buccal mucosal bleeding time.  
• BUN = blood urea nitrogen.  
• CHF = congenital hepatic fibrosis.  
• CuAH = copper associated hepatopathy.  
• DIC = disseminated intravascular coagulation.  
• DPM = ductal plate malformation.  
• ECM = extracellular matrix.  
• EHBDO = extrahepatic bile duct occlusion.  
• GI = gastrointestinal.  
• HE = hepatic encephalopathy.  
• IBD = inflammatory bowel disease.  
• NSAID = nonsteroidal anti-inflammatory drug.  
• PHS = postcentesis hypotension syndrome.  
• PIVKA = proteins invoked by vitamin K 
absence or antagonism.  
• PPC = polyenylphosphatidylcholine.  
• PT = prothrombin time.  
• PU/PD = polyuria/polydipsia.  
• RBC = red blood cell.  
Center SA. Metabolic, antioxidant, nutraceu-
tical, probiotic, and herbal therapies relating 
to the management of hepatobiliary disorders. 
Vet Clin North Am Small Anim Pract 2004, 
34:67–172.
Eulenberg VM, Lidbury JA. Hepatic fibrosis 
in dogs. J Vet Intern Med. 2018, 32:26–41.
Strickland JM, Buchweitz JP , Smedley RC, 
et al. Hepatic copper concentrations in 546 
dogs (1982–2015). J Vet Intern Med 2018, 
32:1943–1950.
Webster CRL, Center SA, Cullen JM, et al. 
diagnosis and treatment of chronic hepatitis 
in dogs. J Vet Intern Med 2019, 
33(3):1173–1200.
Authors  Alysha Vincent and Kate Holan
Sharon A. Center.

282  Blackwell’s Five-Minute Veterinary Consult  
CClaw and Clawfold Disorders
 BASICS
• Ungual fold—crescent-shaped tissue 
surrounding the proximal claw.
• Coronary band and dorsal ridge (dorsal 
ridge of the ungual crest)—produces most of 
the claw; contributes to the curvature of the 
claw.
• Paronychia—inflammation of soft tissue 
around the claw.
• Onychomycosis—fungal infection of the 
claw.
• Onychorrhexis—brittle claws that tend to 
split or break.
• Onychomadesis—sloughing of the claw.
• Onychodystrophy—deformity caused by 
abnormal growth; often a sequela of a 
disorder.
• Onychomalacia—softening of the claw.
• Claws and ungual folds—subject to trauma, 
infection, vascular insufficiency, immune-
mediated disease, parasites, neoplasia, defects 
in keratinization, and congenital abnormal- 
ities.
• A particular claw deformity may be 
caused by a variety of diseases—claw disease 
is most often associated with other dermatoses: 
rarely the only epithelial structure affected.
• A single disease can present with various 
claw lesions.
• One foot affected—top differentials include 
foreign body, neoplasia, trauma, fungal 
infection, bacterial infection.
• Multiple feet affected—allergy, endocrine, 
secondary infections, demodicosis, 
immune-mediated disorders, epidermolysis 
bullosa, symmetric lupoid onychodystrophy 
(SLO), plasma cell pododermatitis, super  - 
ficial necrolytic dermatitis, nutritional deficien -
cies, psychogenic dermatoses, idiopathic.
• Claw and clawfold diseases—1.3% of dogs 
and 2.2% of cats.
• Mean age range—SLO 3–8 years.
• No predominant sex reported.
• Dachshunds—onychorrhexis.
• German shepherd dogs, Rottweilers, 
possibly giant schnauzers and Doberman 
pinschers—SLO.
• Siberian huskies, dachshunds, Rhodesian 
ridgebacks, Rottweilers, cocker spaniels— 
idiopathic onychodystrophy.
• German shepherd dogs, whippets, English 
springer spaniels—idiopathic onychomadesis
• Shorthair dog breeds—paronychia in 
multiple digits.
• Devon Rex cats— Malassezia  paronychia.SIGNS
• Licking at the feet and/or ungual folds.
• Lameness.
• Pain.
• Swelling, erythema, and exudate of ungual fold.
• Deformity or band formation of claw.
• Sloughing of claw.
• Discoloration of claw.
• Hemorrhage from claw or at loss of a claw.
CAUSES
Paronychia
• Infection—bacteria, dermatophyte, yeast 
(Candida , Malassezia ).
• Immune-mediated—pemphigus, bullous 
pemphigoid, systemic lupus erythematosus 
(SLE), drug eruption, SLO.
• Neoplasia—subungual squamous cell 
carcinoma, melanoma, eccrine carcinoma, 
osteosarcoma, subungual keratoacanthoma, 
inverted squamous papilloma.
• Arteriovenous fistula.
Onychomycosis
• Dogs— Trichophyton mentagrophytes — 
usually generalized.
• Cats— Microsporum canis .
Onychorrhexis
• Idiopathic—especially in dachshunds; 
multiple claws.
• T rauma.
• Infection—dermatophytosis, leishmaniasis.
Onychomadesis
• T rauma.
• Infection.
pemphigoid, SLE, drug eruption, SLO.
• Vascular insufficiency—vasculitis, cold 
agglutinin disease.
• Neoplasia—see above.
• Idiopathic.
Claw Dystrophy
• Feline hyperthyroidism.
• Zinc-responsive dermatosis.
• Congenital malformations.
• Leishmaniasis.
 DIAGNOSIS
• T rauma or neoplasia often affects a single 
claw.
• Involvement of multiple claws suggests a 
• Immune-mediated diseases (except SLO) 
usually have other skin lesions in addition to 
claw or ungual fold lesions.
May show evidence of SLE, diabetes mellitus, 
hyperthyroidism, or other systemic illness.OTHER LABORATORY TESTS
• Feline leukemia virus (FeLV).
• Serum thyroxine.
• Antinuclear antibody (ANA) titer.
IMAGING
Radiographs—osteomyelitis of third phalanx, 
neoplastic change.
• Biopsy—often involves a third phalanx 
amputation; inclusion of the coronary band 
required for diagnosis of most diseases; punch 
biopsy of the claw (onychobiopsy).
• Cytology of exudate from the claw and/or 
fold.
• Bacterial and fungal culture.
 TREATMENT
PARONYCHIA
• Surgical removal of claw plate (shell).
• Antimicrobial soaks.
• Systemic antibiotics as per culture results.
• Identify underlying condition and treat 
specifically.
• Antifungal soaks—chlorhexidine, povidone 
iodine, lime sulfur.
• Surgical removal of claw plate—may 
improve response to systemic medication.
• Amputation of third phalanx.
• Repair with fingernail glue (type used to 
attach false nails in humans).
• Remove splintered pieces and maintain 
with rotary sander (Dremel).
• T reat underlying cause.
• Amputate third phalanx, last resort.
Neoplasia
• Determined by biologic behavior of specific 
tumor.
• Surgical excision.
• Amputation of digit or leg.
• Chemotherapy and/or radiation therapy.
T reat underlying cause.
• Bacterial paronychia—systemic antibiotics 
based on culture and sensitivity.
• Yeast paronychia— Candida  or Malassezia  
paronychia: ketoconazole (5–10 mg/kg PO 
q12–24h); topical nystatin or miconazole.

Canine and Feline, Seventh Edition  283
C(continued)  Claw and Clawfold Disorders
• Onychomycosis—griseofulvin (50–150 mg/
kg PO/day) or ketoconazole (5–l0 mg/kg PO 
q12h) for 6–12 months until negative 
cultures; itraconazole (10 mg/kg PO q24h) 
for 3 weeks and then pulse therapy until 
resolved.
• Onychomadesis—determined by cause; 
immunomodulation therapy for immune-
mediated diseases (e.g., SLO); options include 
essential fatty acid supplementation; cycline 
antibiotics: tetracycline 250 mg PO TID for 
dogs <10 kg; 500 mg PO TID dogs >10 kg); 
doxycycline 10 mg/kg PO q24h; minocycline 
5 mg/kg PO BID, often administered with 
niacinamide 250 mg PO for dogs <10 kg and 
500 mg PO for dogs >10 kg; pentoxifylline 
10–15 mg/kg PO BID to TID; corticoster-
oids and cyclosporine 5 mg/kg PO q24h; 
vitamin E; appropriate chemotherapeutic 
agents (e.g., azathioprine, chlorambucil).
(NSAIDs) or tramadol if pain is present.
• Griseofulvin—teratogenic; may cause bone 
marrow suppression, anorexia, vomiting, and 
diarrhea; absorption enhanced if given with a 
high-fat meal.
• Ketoconazole—avoid use in cats; may cause 
anorexia, gastric irritation, hepatic toxicity, 
and lightening of the hair coat. FOLLOW-UP
• Slow claw growth cycle may require 6–8 
months of therapy to fully correct an 
abnormality; improvement may be noted 
after 6–8 weeks of appropriate treatment.
• Bacterial or yeast paronychia and 
onychomycosis—treatment may be 
prolonged and response may be influenced 
by underlying factors; weight reduction in 
obese patients.
• Onychorrhexis—may require amputation 
of the third phalanx for resolution.
• Onychomadesis—prognosis determined by 
underlying cause; immune-mediated diseases 
and vascular problems carry a more guarded 
prognosis than do trauma or infectious causes.
• Neoplasia—excised by amputation of the 
digit; malignant tumors metastasize by the 
time of diagnosis.
• FeLV = feline leukemia virus.• NSAID = nonsteroidal anti-inflammatory 
drug.
• SLO = symmetric lupoid onychodystrophy.
Companion: Small Animal Dermatology, 
3rd ed. Hoboken, NJ: Wiley-Blackwell, 
2018.
2013.
Resnick
Karen Helton Rhodes.

284  Blackwell’s Five-Minute Veterinary Consult  
CClostridial Enterotoxicosis
 BASICS
A complex disorder characterized by diarrhea 
in dogs and cats associated with Clostridium 
perfringens  enterotoxins (CPEs).
• Clostridium perfringens  (CP) is a Gram-
positive, spore-forming, strictly anaerobic 
bacterium. •  CP is a normal commensal 
organism found in the intestinal tract of 
humans and animals. •  A strong link between 
canine acute hemorrhagic diarrhea syndrome 
(AHDS; formerly hemorrhagic gastroenteritis 
[HGE]) and the presence of CP has been 
identified. •  Certain strains of CP (primarily 
Type A) produce a potent enterotoxin (CPE) 
as well as pore-forming toxins (NetE and 
NetF). •  CPE is a cytotoxic enterotoxin that 
causes tissue destruction; it has been identified 
in the feces of up to 14% of dogs without 
diarrhea, thus its role in causing diarrhea is 
unclear. •  NetF-producing CP isolates have 
not been found in healthy dogs. •  Not all 
strains of CP produce CPE or NetF and not all 
dogs that have CPE in feces are clinical, 
therefore it is undetermined why some develop 
diarrhea. •  CPE production is coregulated 
with sporulation of the organism; conditions 
that precipitate sporulation in animals include 
a sudden change in diet, dietary indiscretion, 
injudicious use of antibiotics causing a severe 
dysbiosis, and underlying intestinal disease.
Gastrointestinal (GI).
Incidence is unknown; up to 34% of canine 
diarrhea cases are suspected to be CP related. 
The infection is far less common in cats.
Species
Any age.
SIGNS
Can include both large and small bowel 
diarrhea.
• Large bowel diarrhea—tenesmus, mucous, 
frank blood, and increased frequency of 
defecation. •  Small bowel diarrhea—large 
volumes of soft to liquid diarrhea. •  Vomiting 
and abdominal discomfort. •  Severity varies 
from mild, self-limiting diarrhea to fatal, 
acute, hemorrhagic diarrhea.
• Abdominal discomfort. •  Hematochezia.
• Mucoid feces. •  Dehydration if there has been voluminous diarrhea or vomiting. 
• Fever is uncommon. •  Evidence of systemic 
illness or debilitation is rare.
CAUSES
• In humans, CP-associated diarrhea is 
usually due to ingestion of enterotoxigenic 
isolates. In dogs, it is thought to be secondary 
to disruption of the intestinal microenviron-
ment. •  Anything that disrupts normal enteric 
microbiota can lead to CP overgrowth and 
diarrhea. •  CP toxins have been implicated in 
dogs with AHDS.
• Dietary changes. •  Antibiotic use. • Stress. 
• Primary small intestinal bacterial 
overgrowth.
 DIAGNOSIS
• Diagnostic testing should occur during the 
acute phase. •  In the absence of sepsis, 
antibiotic therapy has not been shown to 
alter resolution of clinical signs, therefore 
response to antibiotics cannot be used as 
diagnostic criterion.
Any cause of diarrhea can be considered, 
including, but not limited to, viral, bacterial, 
or parasitic infection, dietary indiscretion, 
chronic enteropathy, metabolic disease, 
• If dehydration is present—increased 
packed cell volume (PCV) from hemocon -
centration, increased total plasma protein, 
increased amylase, and increased blood urea 
nitrogen (BUN) from prerenal azotemia. 
• Dogs with AHDS will often have 
increased PCV with discordantly low total 
plasma protein. •  Leukocytosis with 
neutrophilia and monocytosis. •  Decreased 
albumin secondary to loss and decreased 
production. •  Increased alanine aminotrans -
ferase (ALT) and aspartate aminotransferase 
(AST) activities from organ hypoxia 
secondary to hypovolemia.
There is no gold standard diagnostic test for 
confirming CP-associated diarrhea.
• Fecal culture alone should not be used to 
diagnose CP-associated illness because the 
organism is a normal commensal; CP can 
be isolated from feces of >80% of healthy 
dogs and 43–63% of normal cats. •  Fecal 
endospore cultures are not useful, as 
sporulation of enterotoxigenic strains of 
CP occurs in dogs with and without 
diarrhea.Enterotoxin Assay
• Fecal ELISA for identification of CPE in 
patients with diarrhea suspected to be due to 
CP is the current recommendation; since 
CPE is present in the feces of 5–14% of 
clinically normal dogs, this may or may not 
be clinically useful. •  Fecal ELISA should be 
run in conjunction with PCR to detect 
enterotoxigenic strains. •  Real-time polymer-
ase chain reaction (RT-PCR) for detection of 
the CPE gene and the alpha toxin gene is 
available; the CPE gene has been found in up 
to 33.7% of healthy dogs, therefore its 
presence in a dog with GI disease does not 
confirm that CP is the cause.
Fecal Cytology
• CP endospores, characterized by “safety-
pin” appearance with oval form and dense 
body at one end of spore wall, can be seen on 
microscopic evaluation of heat-fixed thin fecal 
smear stained with Romanowsky-type stain 
(e.g., Diff-Quik®), Wright’s stain, or new 
methylene blue. •  High numbers of CP 
endospores on fecal cytology correlates poorly 
with clinical disease or fecal CPE activity. 
•  High numbers of fecal endospores can be 
found in feces of healthy dogs.
• Abdominal ultrasound can help rule out 
other causes of GI disease. •  Colonoscopy 
and endoscopy with biopsy can be used to 
confirm presence of acute mucosal necrosis 
and neutrophilic infiltration, as well as 
adherence of rod-shaped bacteria to these 
necrotic areas, and can rule out other causes 
of GI disease.
• Grossly hyperemic or ulcerated mucosa. •  Acute 
intestinal mucosal destruction and neutrophilic 
infiltration. •  Immunohistochemical staining of 
bacterial plaques on necrotic areas may be 
clostridial antigen positive.
 TREATMENT
• There are no research-based recommenda-
tions for optimal treatment of patients with 
CP-associated illness. •  If vomiting or 
diarrhea is not severe, animals may be treated 
as outpatients with antiemetics and subcuta-
neous fluids. •  If more severe diarrhea, 
vomiting, dehydration, or evidence of 
hypovolemia, hospitalization with IV 
replacement crystalloids and antiemetics is 
DIET
• Diet change plays a role in treatment and 
management of cases with chronic recurring 
disease; diets high in either soluble (ferment-
able) or insoluble fiber often result in clinical 
improvement by reducing enteric CP

Canine and Feline, Seventh Edition  285
Cnumber, possibly through acidification of the 
distal intestine, which limits CP sporulation 
and enterotoxin production.
• Commercial diets can be supplemented 
with psyllium (1/2–2 tsp/day) as a source of 
soluble fiber.
• Diets low in fiber should be supplemented 
with fiber (coarse bran 1–3 tbs/day) as a 
source of insoluble fiber or psyllium added as 
a source of soluble fiber. •  Probiotics might 
help restore the normal intestinal microbiota, 
thereby reducing risk of recurrent CP -
associated diarrhea.
• Acute disease is often self-limiting. •  There 
have been no documented reports of trans  - 
mission of CP from animals to humans; 
however, if there are immunosuppressed 
members in the household, strict hygiene 
protocols should be followed.
• Maropitant—1 mg/kg IV/SC q 24h. 
• Ondansetron—0.5–1 mg/kg IV/PO q24h.
• Antibiotics are unnecessary in animals with 
mild disease as the infection is typically 
self-limiting. •  If signs of systemic disease or 
sepsis are present, antibiotics should be 
administered. •  Antibiotics that are recom-
mended are ampicillin: 22 mg/kg IV q8h; 
amoxicillin: 22 mg/kg PO q8h; metronida-
zole: 10–25 mg/kg IV/PO q12h for 5–7 days; 
tylosin: 5–10 mg/kg PO q24h. 
• Tetracyclines are no longer recommended 
due to resistance of CP isolates.
ALTERNATIVE DRUGS(S)
• Probiotics (e.g., lactobacillus) may alter the 
intestinal microbiota, reducing likelihood of 
recurrences. •  One study reported faster 
resolution of clinical signs with use of probiotics than with no treatment. •  Diet 
change can be instituted following resolution 
 FOLLOW-UP
• Ensure adequate hydration and intravascu-
lar volume, with replacement fluid adminis-
tration as needed. •  Monitor PCV, total 
plasma protein, acid-base balance, and 
electrolyte concentrations.
• Regular use of high-fiber diets or probiot-
ics. • Avoiding or anticipating stressful events 
(e.g., kenneling) and using anxiolytics.
• Overall excellent prognosis; many animals 
will have resolution of clinical signs without 
in-hospital treatment. •  Acute hemorrhagic 
diarrheal events should be addressed with 
aggressive resuscitation and hospitalization; if 
the animal responds to therapy, the prognosis 
is good.
• CP enterotoxicosis can be associated with 
AHDS. •  The connection to chronic 
enteropathies is less well understood.
Unknown
Antibiotic therapy may be contraindicated.
SEE ALSO
• Colitis and Proctitis.
• Small Intestinal Dysbiosis.
• AHDS = acute hemorrhagic diarrhea 
syndrome.• ALT = alanine aminotransferase.
• CP = Clostridium perfringens .
• CPE = Clostridium perfringens  enterotoxin.
• HGE = hemorrhagic gastroenteritis.
• RT-PCR = real-time polymerase chain 
reaction.
Albini S, Brodard I, Jaussi A. Real-time 
multiplex PCR assays for reliable detection 
of Clostridium perfringens toxin genes in 
animal isolates. Vet Microbiol 2008, 
127:179–185.
ACVIM Consensus Statement: enteropath-
ogenic bacteria in dogs and cats: diagnosis, 
epidemiology, treatment, and control. J Vet 
Intern Med 2011, 25:1195–1208.
Minamoto Y, Dhanani N, Markel ME, et al. 
Prevalence of Clostridium perfringens, 
Clostridium perfringens enterotoxin and 
dysbiosis in fecal samples of dogs with 
diarrhea. Vet Microbiol 2014, 174:463–473.
Weese SJ, Staempfli HR, Prescott JF , et al. 
The roles of Clostridium difficile and 
enterotoxigenic Clostridium perfringens in 
diarrhea in dogs. JVIM 2001, 15:374–378.
Ziese AL, Suchodolski JS, Hartmann K, et al. 
Effect of probiotic treatment on the clinical 
course, intestinal microbiome, and toxigenic 
Clostridium perfringens in dogs with acute 
hemorrhagic diarrhea. Plos One 2018, 
13(9):e0204691.
Author  Jennifer Good
Stanley L. Marks.
available online(continued)  Clostridial Enterotoxicosis

286  Blackwell’s Five-Minute Veterinary Consult  
CCoagulation Factor Deficiency
  BASICS
Hemostatic defects characterized by a lack 
of one or more procoagulant proteins 
(coagulation factors).
• Coagulation involves a complex series of 
enzymatic reactions that generate a burst of 
thrombin (factor IIa) at sites of blood vessel 
injury; thrombin then cleaves plasma 
fibrinogen into fibrin monomers that 
subsequently polymerize and cross-link to 
form an insoluble fibrin clot.
• Functional and/or quantitative coagulation 
factor deficiencies cause a failure of fibrin clot 
• The liver is the sole or primary site of synthesis 
of most coagulation factors; after synthesis, 
factors II, VII, IX, and X require a vitamin K–
dependent modification to become fully active.
• Coagulation factor deficiency can cause 
spontaneous hemorrhage, prolonged post- 
traumatic hemorrhage, and ultimately blood 
loss anemia.
• Spontaneous hemorrhage—often develops 
in body cavities or potential spaces (i.e., 
hemothorax, hemoperitoneum, hemarthrosis, 
subcutaneous, or intramuscular hematoma).
GENETICS
• Hemophilia A and B (factor VIII and IX 
deficiencies)—X-linked recessive traits.
• All other factor deficiencies are autosomal 
traits.
• Specific defects are more likely to be 
propagated within a single breed, but all breeds 
are at risk for developing new mutations.
• Hereditary factor deficiencies—severe defects 
manifest by 3–6 months of age, milder hemostatic 
defects manifest after surgery or trauma.
• For X-linked recessive traits, males express the 
bleeding tendency, female carriers are clinically 
normal.
• For autosomal traits, males and females 
express signs with equal frequency.
• Hemophilia A is a common hereditary 
factor deficiency and may be seen in all 
breeds and mixed-breed dogs and cats.
• Factor XII deficiency is common in cats, but 
does not cause a clinical bleeding tendency.
• Acquired factor deficiencies—depends on 
underlying disease process.
SIGNS
• Hematoma formation.
• Intracavitary hemorrhage.
• Prolonged hemorrhage after surgery or trauma.
• Blood loss anemia.CAUSES
• Acquired—synthetic failure (liver disease); 
vitamin K deficiency (cholestasis, anticoagulant 
rodenticide toxicity, malabsorption, long-term 
antibiotics, coumadin); factor inhibition 
(anticoagulant overdose, envenomation, 
auto- or alloantibodies); factor consumption 
and depletion (disseminated intravascular 
coagulopathy [DIC]); factor dilution 
(high-volume transfusion, crystalloid, or 
colloid fluid therapy); hyperfibrinolysis 
(secondary fibrinogen depletion).
• Hereditary—distinct mutations in 
coagulation factor genes.
  DIAGNOSIS
• Thrombocytopenia should be the first rule-out 
for any patient with abnormal hemorrhage; 
thrombocytopathies may also cause bleeding 
(see Thrombocytopenia, Thrombocytopathies).
• Hereditary coagulation factor deficiencies cause 
prolongation of coagulation screening tests, 
whereas vonWillebrand disease (vWD) does not.
• Hyperfibrinolysis may cause hemorrhage in 
patients with hypovolemic shock, acute blood 
loss, or trauma, but generally does not cause 
prolongation of activated partial thromboplastin 
time (APTT) or prothrombin time (PT) tests; 
a breed predisposition for hyperfibrinolysis 
may exist in sighthounds.
• Acquired coagulopathies often develop 
because of liver disease, anticoagulant 
rodenticide ingestion, or DIC.
• Liver disease is accompanied by changes in 
the chemistry profile (see Coagulopathy of 
Liver Disease).
• Anticoagulant rodenticide toxicity prolongs 
the PT and/or APTT, but does not affect 
thrombin clotting time (TCT) or fibrinogen 
• DIC always develops secondary to systemic 
disease (especially sepsis, neoplasia, other 
inflammatory conditions) and is often 
accompanied by low or falling platelet count.
• Massive transfusion ( >1 blood volume) 
with stored blood products may dilute 
functional factors, fibrinogen, and platelets 
below hemostatic levels; hypocalcemia may 
also result.
• Contamination of blood samples (e.g., with 
heparin flush) or delayed processing can 
generate spurious PT and APTT abnormalities.
• Regenerative anemia develops over the 
course of days after blood loss.
• Platelet count is normal unless the patient 
has DIC or massive bleeding.
• Resorption of blood from a large hematoma 
may cause hyperbilirubinemia.OTHER LABORATORY TESTS
• Coagulation screening tests (activated 
clotting time [ACT], APTT, PT, TCT) are 
functional tests that measure the time for in 
vitro clot formation; coagulation factor and 
fibrinogen deficiencies prolong clotting time 
(see Figure 1).
• ACT is a point-of-care screening test that 
detects severe deficiencies of all factors (except 
factor VII); ACT may be influenced by 
anemia, thrombocytopenia, and changes in 
blood viscosity.
• APTT is a screening test of the contact 
pathway (prekallikrein, high molecular weight 
kininogen, factor XII), intrinsic system (factors 
XI, IX, VIII), common system (factors X, V, 
II), and severe fibrinogen deficiency.
• PT is a screening test of factor VII, common 
system, and severe fibrinogen deficiency.
• The TCT is a screening test of functional 
fibrinogen and is sensitive to the presence of 
fibrinogen inhibitors.
• Acquired coagulation factor deficiencies 
generally cause prolongation of more than one 
screening test; the most common hereditary 
factor deficiencies (hemophilia and factor XII 
deficiency) specifically prolong APTT.
• Individual factor assays can be performed 
for definitive diagnosis of hereditary or 
complex coagulopathies.
Therapeutic dosages of unfractionated 
heparin, coumadin, and plasma expanders 
(dextran, hetastarch) prolong coagulation 
screening tests.
Results
• Improper sample collection (poor venipuncture 
technique, partially or overfilled citrate collection 
tubes, use of heparin or clot activator tubes) will 
invalidate coagulation test results.
• Extreme lipemia, hemoglobinemia, or 
icterus may interfere with clot detection by 
photo-optical coagulation analyzers.
• Because of factor lability, samples should be 
assayed on site or plasma separated and sent 
on ice to the laboratory.
• Interpretation of coagulation assay 
results requires same-species reference 
intervals and controls; for example, human 
APTT values are generally twice those of 
• The laboratory should confirm cross-
reactivity of antigenic assays and optimization 
of functional tests for animal species.
Buccal mucosal bleeding time (BMBT) is 
prolonged in patients with severe thrombocyto -
penia, platelet dysfunction, vWD, and 
fibrinogen deficiency, but BMBT is insensitive 
to coagulation factor deficiencies.

Canine and Feline, Seventh Edition  287
C
  TREATMENT
• T ransfusion of fresh whole blood, fresh 
plasma, and fresh frozen plasma will supply 
all coagulation factors.
• Cryoprecipitate is a specific source of factor 
VIII, fibrinogen, and von Willebrand factor; 
cryo-supernatant plasma supplies all other factors.
• Component therapy is preferred for surgical 
prophylaxis and nonanemic patients to prevent 
red cell sensitization and volume overload.
• Patients with severe acquired or hereditary 
factor deficiencies may require repeated 
transfusion (q8–12h) to control or prevent 
Vitamin K1 (1.0 to 2.0 mg/kg SQ using a 
small needle, or preferably PO q24h) is an 
effective treatment for patients with anti  - 
coagulant rodenticide poisoning and other 
causes of vitamin K deficiency.
(NSAIDs), anticoagulants, and plasma 
expanders should be avoided to prevent 
further compromise of hemostasis.
• IM injections and jugular venipuncture 
should be avoided, when possible, because of 
the risk of inducing additional bleeding.• Intravenous administration of vitamin K is 
not recommended because of the risk of 
anaphylaxis.
Antifibrinolytic drugs (aminocaproic acid and 
tranexamic acid) help correct coagulopathy 
due to acute trauma and reduce transfusion 
requirements for orthopedic procedures in 
humans, and have shown benefit to prevent 
postoperative bleeding in greyhounds. These 
drugs may also be used topically (e.g., 
bleeding from tooth extraction).
  FOLLOW-UP
• PT or factor VII assays can be used to 
monitor effectiveness of vitamin K admin -
istration in animals with anticoagulant toxicity; 
test results should normalize after 24–48 hours 
of initiating therapy.
• ACT is a less specific but reasonable 
substitute for monitoring response to 
vitamin K.
• Hereditary defects can be monitored by 
cessation of bleeding, stabilization of 
hematocrit, resolution of hematoma, and, if 
needed, specific factor analyses.
T ransfusion poses a risk of immune and 
nonimmune reactions (see Blood T ransfusion 
Reactions).  MISCELLANEOUS
Patients with hereditary factor deficiencies 
should not be bred.
SYNONYMS
• Coagulation defects.
• Coagulopathies.
SEE ALSO
• Disseminated Intravascular Coagulation.
• Thrombocytopathies.
• ACT = activated clotting time.
• APTT = activated partial thromboplastin time.
• BMBT = buccal mucosal bleeding time.
• TCT = thrombin clotting time.
• vWD = von Willebrand disease.
http://eclinpath.com/hemostasis
Brooks MB and DeLaforcade A. Acquired 
coagulopathies. In: Weiss DJ, Wardrop KJ, eds., 
Schalm’s Veterinary Hematology, 6th ed. Ames, 
IA: Wiley-Blackwell, 2010, pp. 654–660.
Author  Marjory B. Brooks
Consulting Editor  Melinda S. CamusCOAGULA TION SCREENING TESTS:  APT T, PT, TCT
APTT : LONG
PT, TCT: NORMALPT: LONG
APTT , TCT: NORMALAPTT& PT : LONG
TCT NORMALALL TESTS
LONG
INTRINSIC FACTOR
DEFECTS
Factor VIII (Hemophilia A)
Factor IX (Hemophilia B)
Contact Deficiencies 
Factor XI
Factor XII (Hageman trait)
Prekallikrein  
HMW Kininogen EXTRINSIC FACTOR
DEFECTS 
Factor VII  deficiencyCOMMON PATHWAY
OR COMBINED
DEFECTS
Common Pathway 
Factor II (Thrombin)
Factor V
Factor X
Combined Deficiency
Vitamin K dependent factors:
Factor II, VII, IX, XFIBRINOGEN AND
COMBINED DEFECTS
Fibrinogen
Severe deficiency
High concentration inhibitors
Deficiency of fib rinogen and
intrinsic, extrinsic, and
common path way factors
Figure 1 .
Diagnostic algorithm for coagulation factor deficiencies(continued)  Coagulation Factor Deficiency

288  Blackwell’s Five-Minute Veterinary Consult  
CCoagulopathy of Liver Disease
 BASICS
OVERVIEW
• The liver is the sole/primary site of 
synthesis of procoagulant, anticoagulant, and 
fibrinolytic proteins, except factors V, VIII, 
von Willebrand factor (vWF), tissue plasmin  - 
ogen activator (TPA).
• Some patients develop prolonged in vitro 
clotting times, but few exhibit spontaneous 
bleeding.
• Causes of hemostatic imbalance: 
◦ reduced synthesis or activation of 
procoagulant proteins; 
◦ vitamin K deficiency; 
◦ dysfibrinogenemia due to abnormal 
fibrin polymerization; 
◦ reduced clearance of fibrin/fibrinogen 
degradation products (FDP); 
◦ thrombocytopenia or thrombocytopathy; 
◦ enhanced fibrinolysis.
• Vitamin K deficiency—linked to severe 
intra- or extrahepatic cholestasis, steatorrhea, 
or prolonged oral antibiotic administration.
Dog and cat of any age, breed, or sex.
SIGNS
• Often minor or absent.
• Melena, hematemesis, hematochezia, hematuria.
• Prolonged bleeding if provoked—venipunc-
ture, cystocentesis, biopsy, surgical wounds.
• Spontaneous bruising/hematomas—rare 
unless severe vitamin K deficiency or 
fulminant disseminated intravascular 
• Severe hepatic failure of any etiology.
• Acute viral liver disease.
(EHBDO).
• Chronic liver disease—especially cirrhosis.
• Concurrent small bowel disease (e.g., cats 
with cholangiohepatitis or hepatic lipidosis) 
predisposing to vitamin K deficiency.
• High central venous pressure (CVP) and 
portal hypertension.
• Portosystemic vascular anomaly (PSVA)—
asymptomatic factor deficiency common; 
overt bleeding uncommon.
 DIAGNOSIS
• Toxicities—see Hepatotoxins.
• Hereditary hemostatic defects.
• DIC—any cause.
• Hepatic amyloidosis.• Abdominal trauma, gastrointestinal 
infiltrative disorders.
• CBC—normal or regenerative anemia; 
microcytosis; thrombocytopenia.
• Biochemistry—high liver enzymes; 
bilirubinemia; low albumin; hypoglobulin -
emia; low cholesterol.
• Urinalysis—hematuria; bilirubinuria.
Hemostatic tests—thrombocytopenia; 
prolonged APTT (activated clotting time 
[ACT]), prothrombin time (PT), thrombin 
clotting time (TCT), and proteins induced by 
vitamin K absence (PIVKA); low fibrinogen 
and coagulation factors; low anticoagulant 
factors (antithrombin [AT], protein C); high 
FDP and D-dimer.
IMAGING
• Effusion (ascites, hemorrhage).
• Liver changes—variable.
• Abnormal enteric motility, thickening in 
area of bleeding.
 TREATMENT
• Not necessary unless invasive procedures 
planned or spontaneous hemorrhage noted.
• Fresh whole blood—provides replacement 
of red cells, coagulation factors, functional 
platelets.
• Fresh frozen plasma—provides coagulation 
factors, other hemostatic proteins, and 
reduces risk of red cell sensitization or volume 
overload.
• Cryoprecipitate—for severe hypofibrino-
genemia or bleeding with coexistent von 
Willebrand’s disease (vWD).
• Platelet-rich plasma—rarely indicated.
• Avoid synthetic colloids if bleeding 
tendencies observed.
Biopsy
• High risk for bleeding—PIVKA, PT, 
APTT, or ACT prolonged by >50%; 
thrombocytopenia <50,000/ μL; prolonged 
mucosal bleeding time.
• Iatrogenic hemorrhage—grave prognosis if 
spontaneous bleeding with undetermined 
cause.
• Hemostasis support—postprocedure 
bleeding.
• Ultrasound-guided needle core—highest 
risk; observe biopsy site for 15 minutes, then 
sequentially over several hours postprocedure.
• Laparoscopy—affords visibility and allows 
hemostasis (cautery, Gelfoam pack biopsy 
site).
• Laparotomy—wedge biopsy; ill-advised in 
patients with overt bleeding. MEDICATIONS
• Based on cause of hepatic abnormality.
• Vitamin K deficiency—parenteral vitamin K1 
(0.5–1.5 mg/kg q12h SC up to 3 doses in 
24h interval initially); vitamin K1 PO 
(Mephyton®, 1 mg/kg q24h) if normal 
enteric bile acid uptake.
• DIC—correct primary disease; consider 
heparin for overt thrombosis (unfractionated 
heparin [UFH]: 200 U/kg q6–12h; or low 
molecular weight heparin [enoxaparin]: 1 mg/
kg q12–24h), dose titration based on clinical 
status and laboratory monitoring (ACT, 
APTT [UFH], heparin anti-Xa activity [all 
heparins]).
• Blood products—fresh whole blood: 
12–20 mL/kg q24h; fresh frozen plasma: 
10–20 mL/kg q12h; plasma cryosupernatant 
(albumin, vitamin K–dependent factors): 
10–20 mL/kg q12h; cryoprecipitate 
(fibrinogen, vWF , factor VIII): 1 U/10 kg or 
dose to effect.
• Desmopressin acetate (DDAVP)—
0.5–1  μg/kg IV in saline; may increase 
coagulation factors, shortens bleeding times, 
reduces bleeding tendencies; empirically used 
for biopsy-induced bleeding.
• Antifibrinolytics—epsilon aminocaproic 
acid (EACA): 100 mg/kg loading, 30 mg/
kg/h up to 8h; tranexamic acid: 25 mg/kg 
q8h; if evidence of hyperfibrinolysis.
• Stored whole blood—may provoke hepatic 
encephalopathy (HE).
• Vitamin K1 (cats)—high dose causes Heinz 
body hemolysis and oxidant liver injury.
• Aspirin or other nonsteroidal anti-  
inflammatory drugs (NSAIDs)—may 
predispose to renal failure, worsen ascites, 
provoke emesis and spontaneous bleeding,
• High-volume transfusion in citrate-based 
anticoagulants (especially in animals <5 kg) 
may induce symptomatic hypocalcemia.
• Avoid provocative procedures—e.g., jugular 
venipuncture or catheter placement, 
cystocentesis, if recognized bleeding 
tendencies.
 FOLLOW-UP
• PT, PIVKA (limited availability), factor 
VII—most sensitive coagulation tests to detect 
vitamin K deficiency; if no improvement after 
48h of vitamin K1 injection, unlikely correction 
by further dosing.

Canine and Feline, Seventh Edition  289
C(continued)  Coagulopathy of Liver Disease
• Heart rate, blood pressure, mucous 
membrane color and refill, packed cell 
volume (PCV), and total solids to monitor 
response if active bleeding.
• Biopsy site—observe immediately and 
sequentially (ultrasonography) for hemorrhage.
• Sample abdominal effusion to differentiate 
hemorrhage from ascites.
• Well-balanced diet replete with vitamins.
• Consider impaired vitamin K availability or 
synthesis from chronic oral antimicrobials.
• Invasive procedures—anticipate bleeding; 
pretreat with vitamin K1; give DDAVP within 
20 min of anticipated biopsy or if bleeding 
tendencies persist despite vitamin K1 therapy 
(repeated DDAVP of no use); fresh frozen 
plasma for factor/fibrinogen replacement and 
active bleeding; avoid volume overload and 
increased CVP .
• Eliminate enteric parasitism.POSSIBLE COMPLICATIONS
Hemorrhage, anemia, hypovolemia, HE.
Spontaneous hemorrhage, refractory 
coagulopathy, and DIC—poor prognosis.
SEE ALSO
• Hepatotoxins.
time.
• AT = antithrombin.
• CVP = central venous pressure.
• DDAVP = desmopressin acetate.
• EACA = epsilon aminocaproic acid.• EHBDO = extrahepatic bile duct 
• FDP = fibrin/fibrinogen degradation 
product.
drug.
• PIVKA = proteins induced by vitamin K 
absence.
• UFH = unfractionated heparin.
• vWD = von Willebrand’s disease.
• vWF = von Willebrand factor.

290  Blackwell’s Five-Minute Veterinary Consult  
CCobalamin Deficiency
 BASICS
OVERVIEW
• Cobalamin deficiency occurs in patients 
with cobalamin malabsorption when all body 
stores of cobalamin have been utilized and 
cobalamin is deficient on a cellular level.
• Cobalamin is required by virtually all cells 
in the body and plays a major role in beta- 
oxidation, conversion of certain amino acids, 
and the formation of tetrahydrofolate, and is 
thus crucial for energy production, amino 
acid metabolism, and DNA and RNA 
• Cobalamin deficiency is associated with 
gastrointestinal (GI) signs and systemic 
complications, such as immunodeficiencies, 
central neuropathies, and peripheral neuro  - 
pathies.
• Cobalamin is absorbed exclusively in the 
ileum of dogs and cats via a receptor-  
mediated mechanism.
• The main causes of cobalamin deficiency in 
dogs and cats include chronic GI disease 
involving the ileum (e.g., inflammatory bowel 
disease, small intestinal dysbiosis, intestinal 
lymphoma), exocrine pancreatic insufficiency 
(EPI), short bowel syndrome, and, in rare 
cases, inherited cobalamin malabsorption or 
dietary deficiencies.
• In the United States, Chinese Shar-Pei have 
a high prevalence of cobalamin deficiency. 
Isolated families of other breeds, such as the 
giant schnauzer, beagle, border collie, and 
Australian shepherd dog, have also been 
described as having cobalamin deficiency.
• No other breed, sex, or age predilections are 
known for canine or feline patients with 
cobalamin deficiency.
SIGNS
• Clinical signs attributable to the underlying 
disease process:
◦ Chronic enteropathy—diarrhea, weight 
loss, vomiting, poor appetite, or others.
◦ EPI—weight loss, failure to thrive, loose 
stools, steatorrhea, polyphagia or pica, 
borborygmus, flatulence.
• Clinical signs attributable to cobalamin 
deficiency—weight loss, failure to thrive, 
poor hair coat, lethargy, anorexia; less 
commonly signs of peripheral and central 
neuropathy such as a plantigrade stance or 
• Intestinal disease involving the distal small 
intestine (i.e., the ileum)—inflammatory 
bowel disease, food-responsive enteropathy, 
lymphoma, others.
• EPI.
• Short bowel syndrome.• Hereditary (Chinese Shar-Pei, giant 
schnauzer, beagle, border collie, Australian 
shepherd dog).
• Dietary—being fed exclusively vegan or 
vegetarian diet without concurrent supple  - 
 DIAGNOSIS
Other diseases causing chronic GI disease, 
immunosuppression, central neuropathies, or 
peripheral neuropathies.
• May be within normal limits.
• May show changes associated with under  - 
lying disease process (e.g., hypoalbuminemia 
in patients with severe inflammatory bowel 
disease).
• May show anemia, neutrophilia with left 
shift, or neutropenia. Rubricytes have been 
documented in cobalamin-deficient dogs and 
have been interpreted as evidence of 
ineffective erythropoiesis. Hypersegmented 
neutrophils can also be observed.
• Serum and urine methylmalonic acid 
concentrations are increased in patients with 
• Decreased or low normal serum cobala -
min concentrations. Studies measuring 
methylmalonic acid in serum from dogs and 
cats have shown that patients with low 
normal serum cobalamin concentrations 
may be cobalamin deficient on a cellular 
level. Note that all assays used for the 
measurement of serum cobalamin concen -
tration in dogs and cats have been devel -
oped for use in humans and thus must be 
analytically validated for dogs and cats 
before routine clinical use. In addition, each 
laboratory should develop specific reference 
IMAGING
Not useful, other than for evaluation of 
underlying intestinal disease.
None for the diagnosis of cobalamin deficiency. 
However, intestinal biopsies may be useful to 
confirm and characterize chronic 
enteropathies.
 TREATMENT
T reatment of the underlying disease process, 
if identified (e.g., inflammatory bowel 
disease, EPI, lymphoma, small intestinal 
dysbiosis). MEDICATIONS
• Cobalamin supplements:
◦ Cyanocobalamin—usually at 1,000  μg/mL 
for parenteral use; or 1,000  μg tablets or 250  μg 
and 1000  μg chewable tablets for oral use.
◦ Hydroxocobalamin—usually at 1,000  μg/
mL; for parenteral use.
◦ Methylcobalamin—usually 1 mg capsule; 
for oral use.
• T raditionally, cobalamin supplementation 
in cobalamin-deficient patients has been 
administered parenterally (usually SC) 
using cyanocobalamin or rarely hydroxo  - 
cobalamin.
◦ Cats receive 250  μg/injection; dogs 
receive between 250  μg (small dog) and 
1,500  μg (giant dog) per injection; doses 
should approximate 50  μg/kg per injection 
within this dose range.
◦ In either species there are 6 weekly 
injections, one more injection a month 
later, and reevaluation of serum cobalamin 
concentration a month later.
• Recent studies have shown that oral 
cobalamin supplementation with cyanoco -
balamin is equally efficacious regardless of 
the underlying cause of cobalamin 
◦ Cats receive 250  μg/day; dogs receive 
between 250  μg (small dog) and 1,000  μg 
(giant dog) per day.
◦ Reevaluation of serum cobalamin 
concentration 2–4 weeks after the last 
dose.
• Continue therapy at the original dosing 
scheme if serum cobalamin is still low; continue 
at a decreased interval if cobalamin is in the 
mid-normal range; discontinue if serum 
cobalamin is in the high end of the reference 
interval.
None known.
 FOLLOW-UP
Depending on the severity of the underlying 
disease process, the complications from 
cobalamin deficiency, and treatment 
response.
• See above; reevaluation of serum cobalamin 
concentration either 1 month after the last 
cobalamin injection or 2–4 weeks after the 
last oral dose of cobalamin.
• Additional monitoring as required for the 

Canine and Feline, Seventh Edition  291
C(continued)  Cobalamin Deficiency
SEE ALSO
• Diarrhea, Chronic—Cats.
• Exocrine Pancreatic Insufficiency.
• Protein-Losing Enteropathy.
• EPI = exocrine pancreatic insufficiency.
• GI = gastrointestinal.INTERNET RESOURCES
http://vetmed.tamu.edu/gilab
Batchelor DJ, Noble P-JM, Taylor RH, et al. 
Prognostic factors in canine exocrine 
pancreatic insufficiency: prolonged survival 
is likely if clinical remission is achieved.  
J Vet Intern Med 2007, 21:54–60.
Berghoff N, Parnell NK, Hill SL, et al. Serum 
cobalamin and methylmalonic acid 
concentrations in dogs with chronic 
gastrointestinal disease. American J Vet Res 
2013, 74:84–89.
Bishop MA, Xenoulis PG, Berghoff N, et al. 
Partial characterization of cobalamin deficiency in Chinese Shar-Peis. Vet J 2011, 
191:41–45.
Maunder CL, Day MJ, Hibbert A, et al. 
Serum cobalamin concentrations in cats 
with gastrointestinal signs: correlation with 
histopathological findings and duration of 
clinical sigs. J Feline Med Surg 2012, 
14:686–693.
Toresson L, Steiner JM, Suchodolski JS, et al. 
Oral cobalamin supplementation in dogs 
with chronic enteropathies and hypocobala-
minemia. J Vet Intern Med 2016, 
30:101–107.
Author  Jörg M. Steiner

292  Blackwell’s Five-Minute Veterinary Consult  
CCoccidioidomycosis
 BASICS
A systemic mycosis caused by the inhalation 
of infective arthroconidia of the soil-borne 
fungus Coccidioides immitis .
• Grows in soil in the mycelial state.  
• Inhalation of infective arthroconidia is the 
primary route of infection; at body tempera-
ture, all but one nucleus is shed and an 
immature spherule is produced within 2–3 
days. • Spherule matures and ruptures, 
releasing 200–300 endospores that can 
produce new spherules. • Neutrophils cannot 
penetrate the spherule wall but can phago -
cytize the endospores. • Fewer than 10 inhaled 
arthrospores are sufficient to cause disease in 
susceptible animals. • Respiratory signs are 
often noted 1–3 weeks after exposure; signs of 
dissemination may not be evident for several 
months. • Most infections are mild or 
subclinical, although dogs appear more 
susceptible than cats to development of 
disseminated disease. • Fever, lethargy, 
inappetence, coughing, and joint pain or 
stiffness may be noticed. • Dissemination 
may occur within 10 days, resulting in signs 
related to the organ system involved; skin 
lesions are usually associated with 
dissemination.
• Respiratory—site of initial infection.  
• Extrapulmonary—musculoskeletal, 
ophthalmic, cardiovascular, skin, neuromus-
cular, reproductive, and visceral organs.
Not an uncommon disease in endemic areas, 
rare in nonendemic areas. It occurs more 
commonly in dogs and rarely in cats.
• C. immitis  is found in the southwestern 
United States in the geographic Lower 
Sonoran life zone. • More common in 
southern California, Arizona, and southwest 
Texas. • Less prevalent in New Mexico, 
Nevada, and Utah.
Species
None
Though most commonly diagnosed in young 
animals (<4 years of age), it is seen in animals 
of all ages.
NoneSIGNS
• Coughing (ranges from dry/harsh to wet/
productive). • Fever unresponsive to anti  - 
biotics. • Anorexia, weight loss. • Weakness, 
lameness (bone or joint involvement).  
• Seizures, paraparesis, back and neck pain 
(CNS involvement). • Visual changes 
(ophthalmic involvement).
Dogs
• Signs with pulmonary involvement—
coughing and dyspnea. • Fever. • Bone 
swelling, joint enlargement, and lameness.  
• Lymphadenomegaly, skin lesions, and 
draining tracts. • Neurologic dysfunction 
including ataxia, spinal or cranial nerve 
deficits, and behavioral changes. • Blindness, 
uveitis, keratitis, and iritis.
Cats
Like dogs, although skin lesions are most 
common type of infection in cats.
CAUSES
C. immitis  grows several inches deep in the soil, 
where it survives high ambient temperatures 
and low moisture. After a period of rainfall, the 
organism returns to the soil surface where it 
sporulates, releasing many arthroconidia that 
disseminate by wind and dust storms.
• Aggressive nosing in contaminated soil and 
underbrush may expose susceptible animals to 
large numbers of arthroconidia. • Dust storms 
after the rainy season; increased incidence noted 
after earthquakes. • Land development with 
earth disruption may lead to increased exposure.
 DIAGNOSIS
• Pulmonary lesions may resemble those of 
other systemic mycoses (e.g., histoplasmosis, 
blastomycosis) or neoplasia (single mass or 
multiple nodules). • Lymphadenomegaly may 
be seen in lymphoma, other systemic mycoses, 
and localized bacterial infections. • Bone 
lesions may resemble those caused by primary 
or metastatic bone tumors or bacterial osteo  - 
myelitis. • Skin lesions must be differentiated 
from routine abscesses or other infective 
processes. • For seizures and ataxia, consider 
inflammatory and neoplastic etiologies.
• Hemogram—mild nonregenerative anemia, 
neutrophilic leukocytosis, monocytosis.  
• Serum chemistry profile—hyperglobuline-
mia, hypoalbuminemia, other changes may 
be consistent with organ of involvement.  
• Urinalysis—proteinuria with inflammatory 
glomerulonephritis.OTHER LABORATORY TESTS
• Serologic tests (generally by agar gel 
immunodiffusion [AGID] or ELISA) for 
antibody to C. immitis  may provide a 
presumptive diagnosis; may aid in monitoring 
response to therapy. • Antigen testing has not 
proven to be sensitive.
IMAGING
• Radiography of lung (interstitial infiltrates, 
granulomas, tracheobronchial lymphadenopa-
thy) and bone lesions (osteolysis) may aid in 
diagnosis. • MRI may help in diagnosing 
granulomas in the CNS.
• Serologic testing; repeat serology titers in 
4–6 weeks when low titers are accompanied by 
clinical signs. • Microscopic identification of 
the large spherule form of C. immitis  in lesion 
or biopsy material is the definitive method of 
diagnosis (large 10–80  μm round, double-
walled structure containing endospores).  
• Lymph node aspirates and impression smears 
of skin lesions or draining exudate may yield 
organisms. • Cultures should be performed by 
trained laboratory personnel using protective 
hoods. • Biopsy of infected tissue often is 
preferred to avoid false-negative results; tissues 
involved, however, may not be readily accessible 
and finding the organism can be challenging; 
therefore, serologic testing is often a more 
logical approach.
• Granulomatous, suppurative, or pyogranu-
lomatous inflammation present in many 
tissues. • Presence of the characteristic 
spherule forms in affected tissues.
 TREATMENT
• Generally treated as outpatient.  
• Concurrent clinical symptoms (e.g., seizures, 
pain, coughing) should be treated appropriately.
ACTIVITY
Restrict activity until clinical signs begin to 
subside.
DIET
Feed a high-quality palatable diet to maintain 
body weight.
• T reatment is potentially long ( >6–9 
months) and expensive. • Relapse (especially 
with disseminated disease) is common.  
• Reassure client that infection is not 
zoonotic.
In cases of focal granulomatous organ 
involvement (e.g., consolidated pulmonary 
lung lobe, eye, kidney), surgical removal of 
the affected organ may be indicated.

Canine and Feline, Seventh Edition  293
C(continued)  Coccidioidomycosis
Coccidioidomycosis is considered one of the 
most severe and life-threatening of the 
systemic mycoses. T reatment of disseminated 
disease often requires at least 1 year of 
aggressive antifungal therapy.
Dogs
• Ketoconazole (KTZ)—5–10 mg/kg PO 
q12h; ideally given with food; treatment 
typically requires at least 1 year of therapy; if 
titers rise or clinical signs deteriorate over first 
4–6 weeks of treatment, alternative therapy 
should be considered. • Fluconazole (FCZ)—
10 mg/kg PO q12h; noted to greatly increase 
success of treatment; cost of the drug has 
significantly decreased with availability of 
medical-grade generic compound; treatment 
failures have been noted with use of chemical-
grade compounded formulations.  
• Itraconazole (ITZ)—5 mg/kg PO q12h; 
administered similarly to KTZ, it has been 
reported to have higher penetration rate than 
KTZ; some suggest greater efficacy of ITZ over 
FCZ. • Amphotericin B (AMB) is rarely 
recommended because most patients do not 
require this aggressive therapy and effective 
oral medications are readily available; AMB 
can be administered at a dosage of 0.5 mg/kg 
IV 3 times per week, for a total cumulative 
dosage of 8–10 mg/kg; given IV either as a 
slow infusion (in dogs that are gravely ill) or as 
a rapid bolus (in fairly healthy dogs); for slow 
infusion, add AMB to 250–500 mL of 5% 
dextrose solution and administer as a drip over 
4–6 hours; to lessen adverse renal effects of 
AMB, consider 0.9% NaCl (2 mL/kg/h) for 
several hours before initiating AMB therapy.
Cats
Any of the following azoles may be used in 
cats: KTZ 50 mg total dose PO q12h; FCZ 
25–50 mg total dose PO q12h; ITZ 
25–50 mg total dose PO q12h.
• Drugs metabolized primarily by the liver should 
be used with caution alongside azole drugs.  
• Drugs metabolized primarily by the kidneys 
should be used with caution alongside AMB.
• Side effects of azoles include inappetence, 
vomiting, and hepatotoxicity (typically 
alanine transaminase [ALT] > alkaline 
phosphatase [ALP]); liver values should be 
monitored monthly initially; drugs may be 
stopped until signs abate and restarted at a 
lower dose, which may be slowly increased to the recommended dose if the animal is able to 
tolerate the drug; newer azoles (ITZ and 
FCZ) have fewer side effects. • Side effects of 
AMB therapy can be severe, especially renal 
dysfunction, fever; use with caution if patient 
is azotemic, but not an absolute contraindica-
tion if the infection is life-threatening.
 FOLLOW-UP
• Serologic titers should be monitored every 
3–4 months; animals should be treated until 
clinical and radiographic signs resolve/stabilize 
and their titers ideally fall to less than 1 : 4; 
titers frequently do not become negative 
throughout treatment. • Consider ITZ levels 
(2–4h post pill) in patients showing poor 
response to ITZ therapy, especially if using 
generic or compounded formulation.  
• Creatinine and urinalysis should be 
monitored in all animals treated with AMB; 
treatment should be temporarily discontinued 
if creatinine rises above reference range or 
greater than 20% above baseline, or if 
granular casts are noted in urine.
• No vaccine is available for dogs or cats.  
• Contaminated soil in endemic areas should 
be avoided, particularly during dust storms 
after the rainy season.
Pulmonary disease resulting in severe 
coughing may temporarily worsen after 
therapy is begun owing to inflammation in 
the lungs. Anti-inflammatory short-term  
(2 weeks to 2 months) oral prednisone and 
cough suppressants may be required to 
alleviate the respiratory signs.
• Prognosis for localized respiratory disease is 
good. • Prognosis for disseminated disease is 
guarded; many dogs will improve following 
oral therapy with resolution of signs reported 
in up to 90% cases; however, relapses may be 
common, especially if therapy is shortened; 
overall recovery rate has been estimated at 
60%. • Prognosis with CNS involvement may 
be guarded to poor. • Prognosis for cats is not 
well documented, but long-term therapy 
should be anticipated and relapses are 
common. • Serologic testing every 3–4 
months after completion of therapy is 
recommended to monitor possibility of rising 
titer and potential relapse. • Spontaneous 
recovery from disseminated coccidioidomyco-
sis without treatment is extremely rare. MISCELLANEOUS
• The spherule form of the fungus, as found 
in animal tissues, is not directly transmissible 
to humans or to other animals. • Under 
certain rare circumstances, however, there 
could be reversion to growth of the infective 
mold form of the fungus on or within 
bandages placed over a draining lesion or in 
contaminated bedding; draining lesions can 
lead to contamination of the environment 
with arthrospores; care should be exercised 
whenever handling an infected draining 
lesion. • Special precautions should be 
recommended to households in which the 
owners may be immunosuppressed.
Azole drugs can be teratogenic and should be 
used in pregnant animals only if the potential 
benefit justifies the potential risk to offspring.
SYNONYMS
• Desert rheumatism (in humans).  
• San Joaquin Valley fever. • Valley fever.
• AMB = amphotericin B.
• FCZ = fluconazole.
• ITZ = itraconazole.
• KTZ = ketoconazole.
Arbona N, Butkiewicz CD, Keyes M, et al. 
Clinical features of cats diagnosed with 
coccidioidomycosis in Arizona, 2004–2018. 
J Feline Med Surg 2020, 22(2):129–137.
Graupmann-Kuzma A, Valentine BA, Shubitz 
LF , et al. Coccidioidomycosis in dogs and 
cats: a review. J Am Anim Hosp Assoc 
2008, 44:226–235.
Johnson LR, Herrgesell EJ, Davidson AP , 
et al. Clinical, clinicopathologic, and 
radiographic findings in dogs with 
coccidioidomycosis: 24 cases (1995–2000). 
J Am Vet Med Assoc 2003, 222:461–466.
Shubitz LE, Butkiewicz CD, Dial SM, et al. 
Incidence of coccidioides infection among 
dogs residing in a region in which the 
organism is endemic. J Am Vet Med Assoc 
2005, 226:1846–1850.

294  Blackwell’s Five-Minute Veterinary Consult  
CCoccidiosis
 BASICS
OVERVIEW
• An enteric infection, traditionally associated 
with Cystoisospora canis  (dogs) and Cystoisospora 
felis (cats) as potential pathogens; other 
species of Cystoisospora  may be present.
• Strictly host specific (i.e., no cross-transmission).
• Eimeria  spp. are not parasitic for dogs or 
cats.
• Cryptosporidium  can cause an acute, life- 
threatening coccidiosis (cryptosporidiosis) in 
neonatal pups and kittens; can also cause 
non-life-threatening small bowel diarrhea in 
dogs and cats (see Cryptosporidiosis)
• Voluminous watery diarrhea is characteris-
tic; auto-infection and recycling within the 
intestinal tract result in a rapid loss of 
mucosal lining with cryptosporidiosis.
Dog and cat (especially puppies and kittens).
SIGNS
• Watery to mucoid, sometimes blood-
tinged, diarrhea; vomiting; abdominal 
discomfort; inappetence.
• Weak puppies and kittens.
• Immunocompromised animals.
• Infected dogs or cats contaminating 
environment with oocysts of Cystoisospora  
spp. or Cryptosporidium  spp.
• Stress.
• Immunocompromise.
 DIAGNOSIS
Enteric viral infections and other intestinal 
parasites.
Usually unremarkable; may be hemoconcen-
trated if dehydrated.
N/A
IMAGING
N/A
• Fecal flotation (preferably centrifugation 
flotation technique) for oocysts (distinguish from 
pseudoparasitic Eimeria  sp.); use sucrose solution 
or zinc sulfate; acid-fast stains should be 
considered for detection of Cryptosporidium  spp.
• Direct fluorescent antibody (DFA) assay is 
a sensitive dual assay (can detect Giardia  cysts 
and Cryptosporidium  oocysts very well) and 
can be performed at reference laboratories or 
university parasitology laboratories.• Cystoisospora  oocysts should be 40  μm long; 
cysts of Cryptosporidium  are approximately 
5 μm diameter.
 TREATMENT
• Usually treated as an outpatient.
• Inpatient if debilitated.
• Fluid therapy if dehydrated.
• Sulfadimethoxine—55 mg/kg PO on the 
first day, then 25–50 mg/kg PO q24h for up 
to 10–14 days, or until dog is asymptomatic 
for Cystoisospora  and fecal examination is 
negative for oocysts.
• Sulfadiazine/trimethoprim—15–30 mg/kg 
sulfadiazine PO q24h up to 10 days.
• Amprolium (extra-label)—dogs: 100–
400 mg (total dose) PO q24h for 7 days; cats 
with Cystoisospora : 60–100 mg (total dose) 
PO q24h for 7 days.
• No effective or approved treatment for 
Cryptosporidium —paromomycin 165 mg/kg 
PO q12h for 5 days has been suggested 
(extra-label); however, the drug is potentially 
nephrotoxic and ototoxic in cats and should 
not be used; azithromycin has been used at a 
dosage of 7–10 mg/kg PO q12h for 7 days 
for eradication of Cryptosporidium  spp. in 
dogs and cats; however, efficacy is unknown.
• Ponazuril at 30–50 mg/kg PO q24h for 
1–7 consecutive days in dogs, or 15 mg/kg 
PO q24h for 7 consecutive days in cats; 
treatment can be repeated after 3- to 5-day 
break to increase efficacy; single doses of the 
drug are generally ineffective.
• Toltrazuril—10–30 mg/kg PO q24h for 
1–6 consecutive days in dogs.
Precautions
• Mild gastrointestinal upset with antibiotics.
• Amprolium—not recommended to be used 
for more than 12 consecutive days in puppies, 
exogenous thiamine in high doses may 
decrease efficacy; neurologic abnormalities 
have been reported in some dogs: if observed, 
discontinue medication and begin thiamine 
• Sulfadimethoxine—caution with dimin-
ished hepatic or renal function.
• Sulfadiazine/trimethoprim—potentially 
teratogenic; dog: associated with irreversible 
keratoconjunctivitis sicca, type 1 or type 3 
hypersensitivity (especially in larger-breed 
dogs), thrombocytopenia; cat: anorexia, 
leukopenia, anemia, hematuria.CONTRAINDICATIONS/POSSIBLE 
Sulfa medications—caution in patients with 
preexisting renal or hepatic disease.
 FOLLOW-UP
Fecal flotation (for Cystoisospora  spp. oocysts) 
or DFA (for Cryptosporidium  spp. oocysts) 
1–2 weeks following treatment.
More severe disease in young or immuno-
compromised patients.
SEE ALSO
• Toxoplasmosis.
• DFA = direct fluorescent antibody.
Bowman DD, Lynn RC, Eberhard ML. 
Georgis’ Parasitology for Veterinarians,  
8th ed. St. Louis, MO: Saunders (Elsevier 
Science), 2003, pp. 92–100.
Dubey JP , Greene CE. Enteric coccidiosis.  
the Dog and Cat, 4th ed. St. Louis, MO: 
Elsevier Saunders, 2012, pp. 828–839.
Lappin, MR. Update on the diagnosis and 
management of Isospora  spp. infections in 
dogs and cats. Top Companion Anim Med 
2010, 25(3):133–135.
Author  Gavin L. Olsen

Canine and Feline, Seventh Edition  295
C
Cognitive Dysfunction Syndrome
  BASICS
Syndrome associated with brain aging. 
Leads to alterations in awareness, decreased 
responsiveness to stimuli, deficits in 
learning and memory, agitation, and 
anxiety. Subtle signs seen in early stages of 
cognitive decline may include alterations in 
activity, social interactions and increasing 
anxiety.
• Neuronal loss, decreased frontal lobe 
volume, increased ventricular volume, and 
neurotoxic deposits including lipofuscin and 
beta-amyloid. • Toxic free radicals (reactive 
oxygen species) increase with age because of 
illness and stressors, age-related decline in 
mitochondrial efficiency, and decreased 
clearance mechanisms. • Unclear which 
changes are associated with the clinical signs; 
possible correlation between cognitive 
decline, amount of beta-amyloid in the 
cerebral cortex, and increases in toxic free 
radicals. • Compromised cerebral vascular 
blood flow and infarcts may be contributory. 
• Neurotransmission is compromised; may be 
a decline in catecholamine and cholinergic 
transmission.
• Behavioral. • Nervous.
GENETICS
Unknown; may be genetic factors contrib -
uting to beta-amyloid deposition and the 
age at which it begins to accumulate.
• Clinical signs of cognitive dysfunction 
syndrome (CDS) have been reported to arise 
in 41–68% (or higher) of dogs over 14. 
• Overall prevalence in dogs over 10 
estimated as at least 14.2%. • Clinical signs 
reported to arise in 50% of cats over 15. 
• Prevalence in cats over 10 estimated at 
35%. • Progressive—over 6 months, 24% of 
dogs with mild signs progressed to moderate 
and 42% with no impairment progressed to 
mild.
Species
• Increased prevalence with increasing age. 
• Neuropsychological testing in dogs and cats 
has identified a decline in memory and 
learning as early as 6–8 years of age. • Initial 
signs may not be noticed by pet owners, 
except perhaps in dogs trained to perform 
more specialized tasks (e.g., guide and hearing 
dogs, drug detection, agility).SIGNS
• Clinical signs have been categorized using 
the acronym DISHAA. • Disorientation, 
including getting lost in familiar environ -
ments, confusion, inability to navigate 
through familiar routes (e.g., goes to hinge 
side of door), dropping food and not retrieving. 
• Interactions with humans or other animals 
may be altered (irritability, decreased interest 
in play/affection, or increased attention 
seeking). • Sleep–wake cycle alterations 
including night waking, vocalization, and/or 
increased sleep during the day. 
• Housetraining and other previously learned 
behaviors might deteriorate. • Activity may 
be altered—including a decline in activity 
level, exploration, and self-care; however, as 
the condition progresses, activity may increase 
with signs of restlessness, pacing, aimless 
wandering, vocalization, or excessive licking. 
• Anxiety and agitation.
• No specific abnormalities associated with 
cognitive dysfunction. • Other age-related 
medical disorders might be noted.
CAUSES
• Exact cause is unknown and animals are 
variably affected. • Environmental factors 
may contribute to age-related degeneration. 
• May be predisposing genetic factors. 
• Diet, enrichment, and stress management 
may be in part preventive. • See 
Pathophysiology.
• Chronic oxidative stress and chronic 
low-grade inflammation. • Conditions that 
affect cerebral vascular blood supply (e.g., 
systemic hypertension, anemia). • Deficiency 
in docosahexaenoic acid (DHA), B6, B12, 
and folic acid, high homocysteine, low-
quality diets.
  DIAGNOSIS
• Any medical condition that affects the pet’s 
mental attitude or behavior must be ruled 
out. • Pain (e.g., arthritis, dental disease) can 
lead to increased irritability, anxiety, and 
altered response to stimuli. • If mobility is 
affected, the pet may be less able to avoid 
fearful stimuli and less able to access its 
elimination area. • Impaired sight or hearing 
might lead to decreased responsiveness or 
increased reactivity to stimuli. • Diseases of 
the urinary or gastrointestinal tract can cause 
house-soiling. • Organ failure, tumors, 
immune diseases, and endocrinopathies can 
also affect behavior. • Diseases that affect the 
CNS or its circulation can affect behavior.CBC/BIOCHEMICAL/URINALYSIS
Normal with CDS, but concurrent disease 
processes common in aged dogs.
Normal with CDS.
IMAGING
• Used to rule out primary organic/structural 
cause. • Most important when there are 
abnormalities on the neurologic examination 
or when the onset is sudden; less likely to be 
of diagnostic value if signs are slowly 
progressive in the absence of other neurologic 
findings.
• Diagnosis is based on identifying clinical 
signs on screening questionnaire, e.g., DISHAA 
(Pan et al.), CADEs (Madari et al.), and 
CCDR (Salvin et al.), ruling out possible 
medical causes. • Early and mild signs not 
likely to be reported; therefore veterinarians 
must ask (e.g., with screening questionnaire). 
• Endoscopy, radiography, ultrasound, and 
other specialized diagnostic procedures may 
be necessary to rule out other causes of the 
clinical signs. • Further ophthalmic and 
neurologic assessment if indicated to rule out 
visual or auditory deficits and neurologic 
disease. • Therapeutic trial might be 
considered to rule out and treat other 
potential causes of the signs, e.g., pain.
Loss of frontal and temporal lobe volume, 
neuronal loss, meningeal calcification, 
microhemorrhage and infarcts, beta-amyloid 
deposition and hyperphosphorylated tau.
  TREATMENT
Support and home care by pet owners.
ACTIVITY
• Maintain exercise, play, reward-based 
training, work, feeding enrichment (e.g., 
food-filled toys), and daily routines that are 
appropriate for the pet’s age and health. 
• Maintaining mental stimulation and 
physical activity have been shown to reduce 
or slow progression of cognitive decline.
DIET
• Diet should be fed that meets and 
prioritizes medical and cognitive health care 
needs. • For dogs, diet supplemented with 
antioxidants including vitamins E and C, 
selenium, beta carotene, and flavonoids and 
carotenoids, omega-3 fatty acids, and 
carnitine and alpha lipoic acid (for mitochon -
drial health) has been shown to improve 
memory, learning ability, and clinical signs of 
cognitive dysfunction (Hills Prescription Diet 
b/d). • As cerebral glucose metabolism 
declines with increasing age in dogs, a diet

296  Blackwell’s Five-Minute Veterinary Consult  
Csupplemented with 5.5% medium-chain 
triglyceride (MCT) oil to provide ketone 
bodies as an alternative source of energy for 
aging neurons has been demonstrated to 
improve cognitive function in middle-aged 
and senior dogs (e.g., Purina ProPlan Bright 
Mind 7+®). • A brain support blend 
containing arginine (to enhance nitrous oxide 
synthesis), antioxidants including vitamins C, 
E, and selenium; B vitamins; and omega-3 
fatty acids has been demonstrated to improve 
cognitive function in laboratory studies in 
senior dogs and middle-aged cats. • A 
combination of the brain support blend and 
6.5% MCT supplementation has been 
demonstrated to improve clinical signs of 
cognitive dysfunction in dogs (Purina Pro 
Plan Veterinary Diets NC NeuroCare®). • For 
dogs—supplements containing phosphati  - 
dylserine (Senilife, CEVA Animal Health and 
Activait, VetPlus), S-adenosyl-L-methionine-
tosylate disulfate (SAMe; Novifit, Virbac 
Animal Health), and apoaequorin have 
demonstrated some evidence of efficacy. • For 
cats—SAMe and diets containing fish oil, 
arginine, B vitamins, and antioxidants have 
demonstrated beneficial effects.
• Lifelong therapy is required, and 
concurrent medications may be necessary if 
the pet has multiple problems. • Any changes 
in the pet’s health or behavior should be 
reported immediately, as this may be due to 
cognitive dysfunction or new health problems. 
• Considering the pet’s health and cognitive 
status, the owner must be advised on any 
limitations on what might be achieved. 
• Signs are generally progressive; treatment is 
aimed at slowing the progression of the 
disease, not cure.
Dogs
• Selegiline—monoamine oxidase (MAO) 
B inhibitor, may contribute to improved 
catecholamine transmission, decrease in free 
radicals, and neuroprotective effect; 
0.5–1 mg/kg PO q24h in the morning and 
maintained if effective; reevaluate clinical 
signs for improvement after 1–2 months; 
side effects might include occasional 
gastrointestinal upset and restlessness, and 
repetitive behavior at higher doses. 
• Propentofylline—not licensed in North 
America but is licensed in other countries; 
xanthine derivative; purported to inhibit 
platelet aggregation and thrombus 
formation, make the red cells more pliable, 
and increase blood flow; may increase 
oxygen supply to CNS without increasing 
glucose demand; 3–5 mg/kg PO q12h. • Nicergoline—alpha-adrenergic antagonist 
that may improve cognitive function 
through vasodilatory effects on cerebral 
circulation; 0.25–0.5 mg/kg PO q24h.
Cats
• No therapeutic agents licensed for 
treatment of CDS. • Selegiline (0.5–1 mg/kg 
PO q24h), propentofylline (1/4 of 50 mg 
tablet PO q24h), and nicergoline (0.25–
0.5 mg/kg PO q24h) have been used off-label 
in cats, with anecdotal evidence of effect.
• Selegiline should not be used concurrently 
with MAO inhibitors such as amitraz, 
narcotics, alpha-adrenergic agents such as 
phenylpropanolamine or ephedrine, or 
selective serotonin reuptake inhibitors 
(e.g., fluoxetine) or tricyclic antidepressants 
(e.g., clomipramine). • A 2-week washout is 
suggested following most tricyclic antidepress-  
ants and up to 5 weeks following fluoxetine 
before starting selegiline.
• Choose medications that are least sedating 
and least anticholinergic. • Potential drug 
interactions must be considered with 
concurrent use of drugs and over-the-counter 
See Contraindications.
• Consider potential benefits vs. risks 
including contraindications, side effects, 
off-label use, and evidence of effect. • Anti-
inflammatory medications and natural 
supplements such as gingko biloba and 
curcumin might be considered based on 
preliminary work in other species. 
• Medication used in humans for Alzheimer’s 
disease to enhance cholinergic transmission 
might be useful, but doses and pharmaco -
kinetics in dogs have not been determined; 
side effects might include nausea, vomiting, 
diarrhea, and sleep-wake disturbances. • For 
anxiety, agitation, apathy, and night waking 
consider adjunctive therapeutics including 
buspirone or fluoxetine for ongoing use, or 
trazodone, benzodiazepines, and alpha-2 
agonists for as needed use. • Natural 
supplements including pheromones, 
melatonin, valerian, l-theanine, alpha-
casozepine, γ-aminobutyric acid (GABA), 
magnolia and phellodendron (Solliquin®), or 
Souroubea (Zentrol®) might help to reduce 
signs related to anxiety and night-time 
waking.
  FOLLOW-UP
• If a drug or diet for CDS is dispensed, 
therapeutic response should be evaluated after 30–60 days and the dose adjusted or 
treatment changed if there is insufficient 
improvement. • If the pet is stable, twice-
yearly checkups are recommended unless new 
problems arise before reassessment is due.
• Providing an enriched environment, 
ongoing training, and physical activity that is 
appropriate and practical for the pet’s age and 
health may help to prevent or delay the onset 
of cognitive decline. • Early CDS dietary 
intervention may address risk factors and slow 
the progression of disease.
Diet and medication may improve signs and 
slow progression in most cases; however, with 
increasing age, CDS may progress and other 
concurrent health problems will ultimately 
arise.
SYNONYMS
• Age-related cognitive and affective 
disorders, involutional depression, dysthymia. 
• Dementia. • Senility.
• CDS = cognitive dysfunction syndrome. 
• DHA = docosahexaenoic acid. • GABA = 
γ-aminobutyric acid. • MAO = monoamine 
oxidase. • MCT = medium-chain triglyceride. 
• SAMe = S-adenosyl-L-methionine-tosylate 
disulfate.
Landsberg GM, Madari A, Zilka N., eds. 
Canine and Feline Dementia: Molecular 
Basis, Diagnostics, and Therapy. Cham: 
Springer, 2017.
Madari A, Farbakova J, Katina S, et al. 
Assessment of severity and progression of 
canine cognitive dysfunction syndrome 
using the Canine Dementia Scale 
(CADES). Appl Anim Behav Sci 2015, 
17:138–145.
Pan Y, Landsberg G, Mougeot I, et al. 
Efficacy of a therapeutic diet on dogs with 
signs of cognitive dysfunction syndrome 
(CDS): a prospective double blinded 
placebo controlled clinical trial. Front Nutr, 
2018, doi: 10.3389/fnut.2018.00127.
Salvin HE, McGreevy PD, Sachdev PS, et al. 
The canine cognitive dysfunction rating 
scale (CCDR): a data-driven and ecologi-
cally relevant assessment tool. Vet J 2011, 
188:331–336.
Authors  Gary M. Landsberg and Sagi 
Denenberg
available onlineCognitive Dysfunction Syndrome  (continued)

Canine and Feline, Seventh Edition  297
CCold Agglutinin Disease
 BASICS
OVERVIEW
• Rare type II autoimmune disorder in which 
anti-erythrocyte antibodies have enhanced 
activity at temperatures <99 °F (37.2 °C).
• Cold agglutinins are typically immuno-
globulin (Ig) M, although IgG alone and in 
combination with IgM may result in disease.
• Cold agglutinins cause direct erythrocyte 
agglutination at low body temperatures 
(primarily peripheral microvasculature), 
leading to vaso-occlusive disease, initiated or 
intensified by cold exposure.
• Fixation of complement and hemolysis is a 
warm reactive process occurring at higher 
body temperatures; at those temperatures cold 
agglutinins have eluted off the red blood cells 
(RBCs), lowering the rate of complement 
binding; therefore, acute hemolytic anemias 
are uncommon with this condition.
• Most cold agglutinins cause little or no 
shortening of erythrocyte lifespan.
• High thermal amplitude cold agglutinins 
(rare)—may cause mild chronic hemolysis, 
but exposure to cold may greatly augment 
binding of cold agglutinins and cause 
intravascular hemolysis.
• Rare; genetics, age, breed, and sex predilec  - 
tions unknown.
• Low titer of cold agglutinins (1 : 32 or less) 
may be found in healthy pets without clinical 
significance.
• More likely to occur following exposure to 
cold temperatures.
SIGNS
• Cyanosis of the extremities associated with 
sludging of erythrocyte agglutinates in 
microvasculature.
• Erythema, skin ulceration with secondary 
crusting.
• Dry, gangrenous necrosis of ear tips, tail tip, 
nose, and feet.
• Anemia may cause signs of pallor, tachycar-
dia, tachypnea, icterus, and pigmenturia.
• Idiopathic; cold exposure is a risk factor.
• Secondary disease—associated with upper 
respiratory infection (cats), neonatal 
isoerythrolysis, lead intoxication (dogs), 
Mycoplasma  pneumonia, and neoplasia.
 DIAGNOSIS
• Skin lesions—vasculitis, hepatocutaneous 
syndrome, toxic epidermal necrolysis, 
dermatomyositis, systemic lupus erythematosus (SLE), lymphoma, frostbite, lead poisoning, 
and pemphigus.
• Other causes of anemia (including hemo  - 
lytic anemias).
• Laboratory abnormalities secondary to 
hemolysis, if present.
• Autoagglutination of RBCs may be 
observed at room temperature.
• Cold agglutinins should be suspected when 
blood in heparin or EDTA on a glass slide 
agglutinates spontaneously at room tempera-
ture with enhancement at 39 °F (3.9 °C), and 
the erythrocytes disperse again upon warming 
to 99 °F (37.2 °C).
• If no agglutination can be induced in vitro, 
it will not occur in vivo in extremities.
• Coombs’ test at 99 °F—cold agglutinins 
usually not detected because they may be 
eluted off the erythrocytes during washing; 
thus test requires the use of anti-complement 
factor serum.
• Coombs’ test at 39 °F—incidence of a 
positive result in healthy dogs has been 
reported to be >50%, which may be caused 
by unspecific binding of the reagent itself or 
by binding of naturally occurring nonpatho-
genic low-titer cold agglutinins.
• The globulin class can be established by 
immunoelectrophoresis of the patient’s 
erythrocytes, which may be important for 
prognosis and treatment.
• Dermal necrosis and ulceration with 
possible opportunistic infections.
• Vascular thrombosis, ischemic necrosis.
 TREATMENT
• Hospitalization in a warm environment 
until the disease is nonprogressive.
• Supportive care and wound management.
• Splenectomy is of little benefit in patients 
with IgM-mediated hemolysis, but may be 
helpful in those with IgG-mediated hemolysis.
• Inform the client to keep the patient in a warm 
environment at all times to prevent relapse.
• Exercise restriction.
• In humans, plasmapheresis, IV gamma 
globulins, and rituximab with or without 
fludarabine have been tried.
• IgM cold agglutinins—immunosuppressive 
therapy not very effective against IgM-
mediated disorders, but can be tried (i.e., 
corticosteroids, leflunomide, cyclosporine).• IgG cold agglutinins—immunosuppressive 
therapy.
Use warmed IV fluids if indicated.
 FOLLOW-UP
• Keep patient in warm environments.
• Cold agglutinin disease usually character-
ized by acute onset and rapid progression.
• Prognosis is guarded to fair; recovery may 
take weeks.
SEE ALSO
Anemia, Immune-Mediated.
Dickson NJ. Cold agglutinin disease in a 
puppy associated with lead intoxication.  
J Small Anim Pract 1990, 31:105–108.

298  Blackwell’s Five-Minute Veterinary Consult  
CColibacillosis
 BASICS
• Escherichia coli  (EC)—Gram-negative 
member of the Enterobacteriaceae ; normal 
inhabitant of intestine of most mammals.
• Acute infection of puppies and kittens in 
first week of life characterized by septicemia 
and multiple organ involvement.
• Isolation from stool of young animals—
inconclusive evidence of pathogenic potential 
because it is normal flora; molecular methods 
can assess virulence potential.
• Isolation from blood cultures or internal 
organs—better evidence of causality.
• Infection of older dogs and cats— 
documented; virulence of individual strains 
poorly characterized.
• Virulence factors—not well defined; likely 
EC as a cause of septicemia in neonatal dogs 
and cats reflects balance between immuno-
logic immaturity and intestinal barrier 
function of host and resident enteric EC 
rather than a single virulent strain.
• Enterotoxigenic EC (ETEC), attaching and 
effacing EC (AEEC), uropathogenic EC 
(UPEC), cytotoxic necrotizing factor (CNF) 
+ EC strains—recovered from dogs, similar in 
cats.
• Intestinal strains colonize and multiply in 
small intestine; ETEC then elaborates 
uncharacterized adhesins and enterotoxins 
(STa); attaching and effacing factor of AEEC 
(intimin [eae]+).
• Many strains of EC from dogs and cats are 
hemolytic.
• An EC reported in boxer dogs with granu  - 
lomatous colitis characterized by ability to 
adhere, invade, and replicate in macrophages, 
resulting in massive inflammatory response 
within intestinal wall.
• Neonates—small intestine (enteritis); 
multiple body systems (septicemia).
• Puppies/kittens and adults—small intestine 
(enteritis); urogenital (cystitis, endometritis, 
pyelonephritis, prostatitis); mammary gland 
(mastitis); large intestine (colitis).
GENETICS
Boxer dogs may be predisposed.
• Few statistics available.
• More common in neonatal puppies and 
kittens <1 week old that have not received 
any or adequate amounts of colostrum.
• Problem in overpopulated kennels and 
catteries.
• Sporadic accounts in older dogs and cats 
(mainly diarrhea and urogenital problems).• Purulent skin disease, otitis, meningoencephalo-  
myelitis.
Dogs
• ETEC—2.7–29.5% of diarrheic dogs; 
strains: STa/STb+/−, and CNF+ isolated from 
diarrheic dogs along with hemolysin.
• β-hemolytic EC—major cause of septice-
mia in newborn puppies exposed in utero, 
during birth, or from mastitic milk.
Cats
• AEEC/enteropathic EC (EPEC)—diarrheic 
cats; strains: eae+, hemolysin.
• Extraintestinal pathogenic EC (ExPEC)—
acute necrotizing and hemorrhagic pneumo-
nia and pleuritis; strains: CNF-1 plus other 
adhesions.
• UPEC—cystitis; strains: CNF-1+, 
P-fimbria, hemolysin.
Worldwide
Species
Boxer dogs may be predisposed to colitis.
• Neonatal infections common (diarrhea, 
septicemia) up to 2 weeks of age.
• Puppies/kittens and adult animals— 
sporadic disease often associated with other 
None
SIGNS
One of the most common causes of septice-
mia and death in puppies and kittens.
• Neonates—sudden-onset vomiting, 
weakness/lethargy, diarrhea, cold skin; one or 
more animals affected in a litter.
• Puppies/kittens and adults—vomiting and 
diarrhea.
• Neonates—acute depression, anorexia, 
vomiting, tachycardia, weakness, hypothermia, 
cyanosis, watery diarrhea.
• Puppies/kittens and adults—ETEC 
associated with acute vomiting, diarrhea, 
anorexia, rapid dehydration, fever.
CAUSES
• EC—endogenous microbial flora of 
adult gastrointestinal tract, prepuce, and 
vagina.
• Many strains; poorly characterized 
regarding virulence factors; need molecular 
methods to assess virulence.
• Often found in older dogs and cats 
concurrently with other infectious agents.RISK FACTORS
Neonates
• Bitch/queen in poor health and nutritional 
status—unable to provide good care and 
colostrum.
• Lack of colostrum or insufficient colostrum.
• Dirty birthing environment.
• Difficult or prolonged labor and birth.
• Crowded facilities—feces in environment, 
chance for fecal–oral spread.
Puppies/Kittens and Adults
• Concurrent disease—parvovirus, heavy 
• Antimicrobial drugs—upset gastrointestinal 
microbial flora.
• Postparturient mastitis.
 DIAGNOSIS
• Infectious enteritis—viral: feline panleuko-
penia, feline leukemia virus, feline immuno-
deficiency virus, enteric coronavirus, canine 
parvovirus, rotavirus, canine distemper; 
bacterial: Salmonella , E. coli , Campylobacter 
jejuni , Yersinia enterocolitica , bacterial 
overgrowth syndrome, Clostridium difficile , 
Clostridium perfringens ; parasitic: hookworms, 
ascarids, whipworms, Strongyloides , Giardia , 
coccidia, cryptosporidia, rickettsiae (salmon 
poisoning).
• Dietary-induced enteritis—overeating, 
abrupt changes, starvation, thirst, food 
intolerance or allergy, indiscretions  
(e.g., foreign material, garbage).
• Drug- or toxin-induced enteritis—antimi -
crobial agents, antineoplastic agents, anthel -
mintics, heavy metals, organophosphates.
• Extraintestinal disorders or metabolic 
diseases—acute pancreatitis; hypoadrenocor-
ticism; liver or kidney disease; pyometra; 
• Functional or mechanical ileus— gastroin -
testinal obstruction, intussusception, 
electrolyte disorder, gastrointestinal foreign 
body.
• Neurologic disorders—vestibular disease, 
psychogenic (e.g., fear, excitement, pain).
• Fading neonates.
• Few abnormalities noted, owing to rapidity 
of death in puppies.
• Adults with enteritis may show nonspecific 
abnormalities, depending on condition.
• Routine bacterial culture and identification 
of EC from blood (antemortem) or necropsy 
tissue (bone marrow, heart blood, liver, spleen, 
brain, mesenteric lymph node) required.

Canine and Feline, Seventh Edition  299
C(continued)  Colibacillosis
• False-negative results can occur if antimi-
crobials are used before obtaining bacterial 
cultures.
• Appropriate testing of strains—identify 
adhesins and toxins (by DNA colony 
hybridization, PCR) in ETEC and verotoxi-
genic EC (VTEC) strains.
• Acute enteritis.
• Inflammation of small intestinal mucosa.
• Petechiae and hemorrhagic lesions on 
serosal surface of gastrointestinal mucosae and 
all body cavities.
• Fibrin on abdominal wall.
• Necrosis of liver/spleen.
 TREATMENT
Acutely ill puppies/kittens—inpatient care.
• Balanced parenteral polyionic isotonic 
solution (e.g., lactated Ringer’s)—restore fluid 
balance.
• Oral hypertonic glucose solution—for 
secretory diarrhea, as indicated.
ACTIVITY
Acutely ill immature puppies/kittens 
(bacteremic/septicemic)—restricted activity, 
cage rest, monitoring, and warmth.
DIET
Puppies—likely to still be nursing when 
affected; good nursing care needed with 
bottle-feeding and/or IV nutrients.
Neonates—life-threatening with poor prognosis.
• Antimicrobial therapy—septicemia.
• Guided by culture and susceptibility (and 
minimal inhibitory concentration) testing of 
EC; empiric therapy until results available. 
Extended-spectrum β-lactamase (ESBL)  
and/or plasmid mediated AmpC (pAmpC) 
strains becoming more common.
• Amikacin—dog and cat: 15–20 mg/kg IV 
q24h.
• Cefazolin—dog and cat: 15–35 mg/kg IV 
q6–8h.
• Cefoxitin—dog and cat: 30 mg/kg IV once, 
then 15 mg/kg IV q6–8h.• Enrofloxacin—dog: 10–15 mg/kg IM/IV 
q24h; cat: 5 mg/kg IV q24h.
• Ticarcillin–clavulanate—dogs and cats: 
50 mg/kg IV q6h.
Fluoroquinolones—avoid use in pregnant, 
neonatal, or growing animals (medium-sized 
dogs <8 months of age; large or giant breeds 
<12–18 months of age) because of potential 
cartilage lesions.
Ensure adequate hydration and perfusion 
when using aminoglycosides.
 FOLLOW-UP
• Physical exam—mentation, rectal 
 temperature, pulse quality.
• Behavior—puppies should be eating, 
drinking, and/or nursing; adequate weight 
gain.
• Bitch/queen—good health; vaccinated; 
good nutritional status.
• Clean and disinfect parturition environ-
ment (1 : 32 dilution of bleach); clean 
bedding frequently after birth.
• Ensure adequate colostrum intake of all 
littermates.
• Separate mother with nursing litter from 
other cats or dogs.
• Keep density low in kennel or cattery 
rooms.
• Wash hands and change clothes and shoes 
after handling other cats/dogs and before 
dealing with neonates.
• Neonates—life-threatening; prognosis often 
poor; neonate may rapidly succumb; quick 
treatment with supportive care essential for 
survival.
• Adults—self-limiting with supportive care, 
depending on degree of dehydration and 
existence of other diseases.
Neonates—greatest risk of infection and 
subsequent septicemia.ZOONOTIC POTENTIAL
• Little information of virulence potential of 
EC strains from dogs or cats for humans, 
although recently similarities have been found 
between canine fecal and UPEC and human 
EC associated with urinary tract infections, 
sepsis, and meningitis.
• Growing concern for presence of multidrug 
resistance determinants in EC strains from 
• Children and immunosuppressed persons 
should be kept away from pets with diarrhea.
• Whole genome sequencing has linked 
commercially available raw meat diets to 
pathogens found in dogs and cats, including 
EC, Salmonella , and Listeria .
SYNONYMS
• E. coli  septicemia.
• Neonatal enteritis.
• AEEC = attaching and effacing E. coli .
• CNF = cytotoxic necrotizing factor.
• EC = Escherichia coli .
• EPEC = enteropathogenic E. coli .
• ESBL = extended spectrum beta-lactamase.
• ETEC = enterotoxigenic E. coli .
• ExPEC = extraintestinal pathogenic E. coli .
• UPEC = uropathogenic E. coli .
• VTEC = verotoxigenic E. coli .
Craven M, Mansfield CS, Simpson KW. 
Granulomatous colitis of boxer dogs. Vet 
Clin North Am Small Anim Pract, 2011 
41:433–445.
control. J Vet Intern Med 2011, 25:1195–208.
Sabshin SJ, Levy JK, T upler T, et al. 
Enteropathogens identified in cats entering 
a Florida animal shelter with normal feces 
or diarrhea. J Am Vet Med Assoc 2012, 
241:331–337.
T upler T, Levy JK, Sabshin SJ, et al. 
Enteropathogens identified in dogs entering 
241:338–343.
Weese JS. Bacterial enteritis in dogs and cats: 
diagnosis, therapy, and zoonotic potential. 
Vet Clin North Am Small Anim Pract 2011, 
41:287–309.

300  Blackwell’s Five-Minute Veterinary Consult  
CColitis and Proctitis
 BASICS
• Colitis—inflammation of the colon (large 
intestine); colitis may be acute and self-  
limiting or chronic. • Colitis does not infer 
causality, and an underlying cause of the colitis 
should be investigated, particularly in chronic 
cases. • Proctitis—inflammation of the rectum.
• Inflammation of the colon causes accumu-
lation of inflammatory cytokines, disrupts 
tight junctions between epithelial cells, 
stimulates colonic secretion, stimulates goblet 
cell secretion of mucus, and disrupts motility. 
• These mechanisms reduce the ability of the 
colon to absorb water and electrolytes, and 
store feces, which causes frequent diarrhea, 
often with mucus and/or frank blood.
Gastrointestinal
GENETICS
• Breeds predisposed to histiocytic ulcerative 
colitis (granulomatous colitis [GC]) include 
boxers, French bulldogs, and, less commonly, 
border collies. • German shepherd dogs are 
predisposed to perianal fistulae (anal furuncu -
losis) that can be associated with colitis.
• Approximately 30% of dogs with chronic 
diarrhea examined at one university hospital. 
• 71% of dogs with a food-responsive 
enteropathy had clinical signs of colitis (either 
alone or in association with enteritis (entero  - 
colitis). • Prevalence of colitis probably higher 
than perceived, because many diarrheic dogs 
and cats manifesting small bowel diarrhea 
have evidence of colitis histopathologically 
when biopsied.
• N/A except for certain infectious diseases.  
• Pythiosis—predominantly Gulf Coast and 
southeast United States, although becoming 
more widespread, including California.  
• Histoplasmosis—Midwest, eastern United 
States. • Prototheca  spp.—ubiquitous in 
nature, especially prevalent in warm, humid 
climates (e.g., southern and southeastern 
United States, northeastern Australia, 
southern continental Europe, Japan) in 
aqueous environments where decaying 
organic matter present. • Entamoeba 
histolytica —prevalent in tropical and 
subtropical regions worldwide; in United 
States, much higher rate of amebiasis-related 
mortality in California and Texas, which 
might be caused by their proximity to  
E. histolytica -endemic areas, such as Mexico, 
other parts of Latin America, and Asia.  
• Tritrichomonas blagburni —widespread distribution in North America, Australasia, 
Europe, and Asia.
Species
• Boxers, French bulldogs, border collies 
(GC). • German shepherd dogs—perianal 
fistulas and concurrent colitis.
• Any age; boxers and French bulldogs are 
typically younger (<2 years). • Cats infected with 
Tritrichomonas blagburni  are typically younger 
(<2 years), but can also be infected when older.
SIGNS
• Fecal consistency can be variable from 
semi-formed to liquid. • Marked increase in 
frequency of defecation (6–15 times per day) 
with small fecal volume. • Tenesmus.  
• Increased fecal mucus. • Hematochezia; cats 
may have formed feces with hematochezia.  
• Occasional dyschezia (painful defecation).  
• Increased urgency to defecate. • Vomiting in 
approximately 30% of dogs and cats with colitis.
• Usually unremarkable. • Rectal examination 
may reveal thickened and irregular colorectal 
mucosa. • Dogs with GC may show systemic 
signs of weight loss and anorexia.
CAUSES
• Dietary—food-responsive enteropathy is 
common and important cause of colitis; 
dietary indiscretion; food intolerance. • Drug 
administration (antibiotics, nonsteroidal 
anti-inflammatory drugs [NSAIDs]).  
• Infectious— Trichuris vulpis , Entamoeba 
histolytica , Balantidium coli , Tritrichomonas 
blagburni , Clostridium perfringens and 
Clostridium difficile , Campylobacter jejuni and 
Campylobacter coli , Yersinia enterocolitica , 
Prototheca , Histoplasma capsulatum , pythiosis/
phycomycosis. • T raumatic—foreign body, 
abrasive material. • Inflammatory—secondary to 
pancreatitis (transverse colitis). • Inflammatory/  
immune—inflammatory bowel disease 
(lymphoplasmacytic, eosinophilic, granuloma -
tous) colitis.
 DIAGNOSIS
• Neoplasia—colonic lymphoma, adenocarci-
noma, sarcomas. • Irritable bowel syndrome. 
• Colorectal polyps do not typically cause 
signs of colitis, but instead cause hematoche-
zia in association with formed stool defecated 
at normal frequency. • Cecal inversion.  
• Ileocecocolic intussusception.CBC/BIOCHEMISTRY/URINALYSIS
• Results usually unremarkable; neutrophilia 
with left shift can be seen with severe 
inflammatory causes; eosinophilia secondary 
to eosinophilic colitis, parasitism, histoplas-
mosis, pythiosis/phycomycosis. • Mild 
microcytic, hypochromic anemia may occur 
secondary to chronic intestinal bleeding  
and iron deficiency. • Hyperglobulinemia in 
some patients (especially cats) with chronic 
disease.
• Examination of fecal centrifugation 
flotation, direct fecal smear (only on fresh 
diarrheic feces), detection of netE and netF 
toxin genes of C. perfringens  and C. difficile  
toxins A and B genes via PCR, serum ELISA 
test for Pythium  when indicated. • Rectal 
scraping for cytology for Histoplasma  
organisms and Prototheca  spp. • Biopsy of 
colon or regional lymph nodes for detection 
of Prototheca  spp., or biopsy of gastrointesti-
nal tract and regional lymph nodes for 
detection of Histoplasma  organisms.  
• Microscopic examination of urine sediment 
or cerebrospinal fluid (CSF) in dogs with 
disseminated protothecosis and associated 
clinical signs can be excellent means of 
detecting organisms. • Culture and sensitivity 
testing for diagnosis of Prototheca  spp.  
• MVista® Histoplasma quantitative antigen 
test performed on serum, plasma, urine, or 
CSF can aid diagnosis and management of 
histoplasmosis. • Fecal PCR or In Pouch TF 
medium for culture of Tritrichomonas foetus .
IMAGING
• Abdominal radiographs—usually unre-
markable. • Abdominal ultrasonography—
may reveal masses, diffuse thickening or 
altered architecture of the colon, or enlarged 
associated lymph nodes. • Contrast studies—
barium may be administered transcolonically 
to evaluate colorectal mucosa for irregularities 
or filling defects and colorectal strictures; 
however, procedure rarely indicated in dogs 
and cats with colitis and of low sensitivity in 
general.
• Colonoscopy with biopsy—procedure of 
choice for diagnosis of chronic or refractory 
cases; animals must be adequately prepared 
for colonoscopy by being fasted and 
administered osmotic cathartics such as 
OsmoPrep® or GoLYTELY®; mucosal changes 
visible grossly in animals with colitis include 
disappearance of submucosal blood vessels, 
granular appearance of mucosa, hyperemia, 
excessive mucus, ulceration, pinpoint 
hemorrhage (small ulcerations), or mass(es).  
• Always obtain multiple biopsy specimens 
from multiple locations (ascending colon, 
transverse colon, descending colon, rectum)

Canine and Feline, Seventh Edition  301
C(continued)  Colitis and Proctitis
because extent of mucosal change assessed 
histologically does not necessarily reflect 
severity of colitis or proctitis.
Histopathologic findings depend on histologic 
type of colitis—lymphoplasmacytic, eosino -
philic, or histiocytic represent most common 
subtypes; hyperplastic mucosa may be seen with 
irritable bowel syndrome; various infectious 
agents may be seen with special stains.
 TREATMENT
DIET
• No inherent benefit to fasting patients with 
diarrhea, unless cause of diarrhea has osmotic 
component. • Animals that do not have severe 
clinical signs can be managed with elimination 
diet or hypoallergenic diet for 2 weeks; 
response to dietary therapy typically seen 
within first 5–7 days following dietary 
implementation; obtain comprehensive dietary 
history to optimize selection of novel, single 
protein source diet; strict dietary compliance 
pivotal during this trial period to optimize 
interpretation of response. • Fiber supplemen -
tation with poorly fermented fiber (e.g., bran 
and alphacellulose) recommended to increase 
fecal bulk, improve colonic muscle contractil -
ity, and bind fecal water to produce formed 
feces. • Some fermentable fiber sources (e.g., 
psyllium or diet containing beet pulp or 
fructooligosaccharides) may be beneficial—
short-chain fatty acids produced by fermenta -
tion may be beneficial for colonocyte function.
Segments of colon severely affected by fibrosis 
from chronic inflammation and subsequent 
stricture formation may need surgical excision, 
especially in patients with granulomatous 
form of disease; cecal inversion and ileoceco-
colic intussusception require surgical 
intervention; pythiosis/phycomycosis often 
requires surgical excision or debulking.
Antimicrobial Drugs
• Trichuris— fenbendazole (50 mg/kg PO 
q24h for 5 consecutive days, repeat in 
3 months). • Entamoeba , Balantidium — 
metronidazole (25 mg/kg PO q12h for 5–7 
days). • Tritrichomonas blagburni —ronidazole 
(30 mg/kg q24h for 14 days). • Clostridium 
perfringens —metronidazole (10 mg/kg PO 
q12h for 5 days), tylosin (5–10 mg/kg PO 
q24h for 5 days), ampicillin or amoxicillin 
(20 mg/kg PO q8h for 5 days); diarrhea, 
including acute hemorrhagic diarrheal syndrome, can be self-limiting and avoidance 
of antimicrobials recommended whenever 
feasible. • Clostridium difficile —metronida-
zole (10 mg/kg PO q12h for 5 days).  
• Campylobacter jejuni —erythromycin 
(10–15 mg/kg PO q8h) or azithromycin 
(5–10 mg/kg PO q24h) can be given for 
7–10 days; azithromycin better tolerated than 
erythromycin. • Yersinia  spp.—select drug on 
basis of bacterial culture and sensitivity 
testing. • Prototheca —combination therapy 
with amphotericin B and itraconazole, 
although disseminated cases typically fatal.  
• Histoplasma —itraconazole (dogs: 10 mg/kg 
PO q24h; cats: 5 mg/kg PO q12h; several 
months of therapy necessary); amphotericin B 
(0.25–0.5mg/kg slow IV q48h up to 
cumulative dose of 4–8 mg/kg) in advanced 
cases. • Pythiosis—itraconazole (10 mg/kg 
PO q24h) and terbinafine (10 mg/kg PO 
q24h) are drugs of choice following surgical 
debridement of affected portions of bowel; 
however, combination of itraconazole, 
terbinafine, and prednisone (without surgical 
resection) was shown to be highly effective in 
small cohort of dogs with focal involvement 
of colon; antifungal therapy often adminis-
tered for 3–4 months or longer in affected 
animals.
Anti-inflammatory 
and Immunosuppressive Drugs 
for Inflammatory/Immune Colitis
• Sulfasalazine (dogs: 25–40 mg/kg PO q8h 
for 3–6 weeks with progressive tapering of 
dose throughout course of drug therapy; cats: 
20 mg/kg PO q12h for 3 weeks); use with 
caution, particularly in cats, in which adverse 
effects on gastrointestinal tract and kidneys 
can be observed; sulfasalazine has been 
associated with irreversible keratoconjuncti -
vitis sicca (KCS). • Corticosteroids—  
prednisone for dogs and prednisolone for 
cats: 1–2 mg/kg PO q12h for 5–7 weeks 
with gradual, progressive tapering of dose; 
most cats can be started on 5 mg (per cat) 
q12h with gradual taper; never use more 
than 50 mg total of prednisone (per day) for 
any animal, regardless of size. • Azathioprine 
(dogs) 1–2 mg/kg PO q24h for 10–14 days, 
followed by taper to 1–2 mg/kg q48h for 4–6 
weeks; drug is markedly myelosuppressive in 
cats and should be avoided even though 
lower dose (0.3 mg/kg PO q48h) for this 
species has been published. • Chlorambucil—  
effective immunomodulator in both dogs 
and cats and usually administered in 
conjunction with prednisone or predniso -
lone; several dosing regimens have been 
published—cats: 2 mg per cat q3–4 days for 
2–3 months (or longer if managing lym -
phoma) or 15 mg/m2 given for 4 consecutive 
days every 3 weeks for 2–3 months; dogs: 
0.1–0.2 mg/kg PO q24h for 8–12 weeks for 
immune disease, with gradual tapering of dose over course of therapy. • Cyclosporine 
(5 mg/kg PO q12–24h for 6 weeks for 
immune disease). • GC (histiocytic ulcerative 
colitis) usually managed with fluoroquinolo -
nes such as enrofloxacin at 10 mg/kg q24h 
for 6–8 weeks; however, evidence of marked 
increase in antimicrobial resistance to this 
class of drugs underscores importance of 
culture and sensitivity testing to optimize 
antimicrobial therapy. • Reconsider diagnosis 
of food-responsive colitis or nonspecific 
colitis carefully in dogs that do not respond 
to dietary therapy, fenbendazole administra -
tion, and tylosin therapy.
Motility Modifiers
• Indicated for symptomatic relief only in 
animals with intractable diarrhea; must be 
avoided in all animals with suspected infectious 
enteropathy. • Loperamide—0.1 mg/kg PO 
q8–12h. • Diphenoxylate—0.1–0.2 mg/kg PO 
q8h. • Propantheline bromide—0.25–0.5 mg/
kg PO q8h, if colonic spasm contributing to 
Anthelminthics
• Broad-spectrum anthelminthics such as 
fenbendazole (50 mg/kg q24h for 5 
consecutive days) or Drontal® Plus in 
conjunction with dietary therapy (elimina -
tion diet) for first 2 weeks is mainstay of 
therapy for most patients with chronic 
colitis, unless a boxer breed that should have 
endoscopy and biopsy to confirm presence of 
GC, which has different therapy and 
prognosis. • Tylosin is highly effective 
antimicrobial that can be administered 
following assessment of response to dietary 
and anthelminthic therapy.
• Monitor patients on sulfasalazine for signs 
of KCS; measure tear production (Schirmer 
tear test) at baseline and every 2 weeks 
throughout course of therapy; discontinue 
drug if tear production decreases; use of 
sulfasalazine therapy has decreased markedly 
over past decade in light of excellent 
response to dietary and tylosin therapy in 
most dogs. • Monitor patients on azathio -
prine for bone marrow suppression—CBC 
every 2–3 weeks; stop treatment or go to 
alternate day if white blood cell count falls 
below 3,000 cells/ μL. • Azathioprine can 
also increase risk of pancreatitis and should 
be used extremely cautiously in any dog at 
increased risk for pancreatitis; azathioprine 
can also cause hepatopathy. • Chlorambucil 
can cause progressive neutropenia and CBC 
should be repeated q2–3 weeks in all animals

should be repeated q2–3 weeks in all animals 
receiving this drug. • Cyclosporine can cause 
hepatotoxicity and chemistry panel should 
be performed as baseline before starting the 
drug and repeated q2–3 months.  
• Amphotericin B is nephrotoxic and 
requires close assessment of renal function

302  Blackwell’s Five-Minute Veterinary Consult  
CColitis and Proctitis  (continued)
via urinalyses and serum biochemistry 
panels. • Enrofloxacin-resistant cases of GC 
are increasing in prevalence due to antimi -
crobial resistance, necessitating alternative 
antimicrobial therapy in select cases.
 FOLLOW-UP
• Infrequent recheck examinations or client 
communication by phone. • Recheck of CBC 
is important for animals on immunomodula-
tory therapy.
• Most bacterial and parasitic infectious 
causes have excellent prognosis, with high 
likelihood of cure following therapy.  
• Prototheca —grave; no known treatment 
except excision and itraconazole and 
amphotericin B following early diagnosis 
and before dissemination. • Histoplasma  
spp.—poor in advanced or disseminated 
disease; mild to moderate cases generally 
respond to therapy. • Pythiosis/phycomyco -sis—poor long-term prognosis in most 
animals, despite surgical intervention, given 
advanced stage of disease at diagnosis; 
addition of anti-inflammatory dose of 
prednisone with antifungal therapy appears 
to enhance effectiveness and benefit of 
therapy. • Cecal inversion, ileocecocolic 
intussusception—good with surgical 
resection if diagnosed in timely fashion. • 
Inflammatory—fair to good with treatment 
in patients with lymphoplasmacytic or 
eosinophilic colitis or GC. • Most dogs with 
mild to moderate nonspecific colitis respond 
favorable to combination of fenbendazole, 
feeding of elimination or hypoallergenic 
diet, and tylosin therapy.
Entamoeba , Balantidium , Campylobacter 
jejuni , Yersinia  in immunosuppressed 
individuals.SYNONYMS
• Inflammatory bowel disease. • Large bowel 
diarrhea.
• GC = granulomatous colitis.
drug.
Marks SL, Kather EJ, Kass PH, et al. 
Genotypic and phenotypic characterization 
of Clostridium perfringens  and Clostridium 
difficile  in diarrheic and healthy dogs. J Vet 
Intern Med 2002, 16:533–540.
Reagan KL, Marks SL, Pesavento PA, et al. 
Successful management of 3 dogs with 
colonic pythiosis using itraconzaole, 
terbinafine, and prednisone. J Vet Intern 
Med 2019, 33(3):1434–1439.
Author  Stanley L. Marks
Consulting Editor  Mark P. Rondeau

Canine and Feline, Seventh Edition  303
CColitis, Histiocytic Ulcerative
  BASICS
OVERVIEW
• Relatively common cause of colitis in 
Boxer breeds and infrequently seen in 
French bulldogs and border collies. • Boxer 
colitis is also referred to as granulomatous 
colitis (GC) in light of the granulomatous 
inflammation (macrophages) in the colon. 
• Etiology of GC is an adherent-invasive  
E. coli  (AIEC) strain.
• Dogs—primarily affects young Boxers, 
usually <3 years of age. • Reported in French 
bulldogs and border collies less frequently.
SIGNS
• Bloody, mucoid diarrhea with marked 
increase in frequency of defecation. • Tenesmus. 
• Weight loss and anorexia can occur and 
debilitation may develop.
GC appears to be a genetic disorder in boxer 
breeds associated with reduced macrophage 
phagocytic function and inability to kill AIEC.
  DIAGNOSIS
• Other causes of colitis—nonhistiocytic 
inflammatory bowel disease (IBD), lymphocytic, 
plasmacytic, eosinophilic colitis, other 
infectious causes of colitis (pythiosis, 
protothecosis, entamoeba), parasitic colitis 
(whipworms), food-responsive diarrhea. 
• Cecal inversion. • Ileocolic intussusception. 
• Neoplasia—lymphoma, adenocarcinoma. 
• Foreign body. • Colorectal polyps—dogs 
with colorectal polyps do not have diarrhea or 
increased mucus in stools, and instead have 
normal defecation frequency with formed 
stools (can have altered shape) coated with 
frank blood. • Irritable bowel syndrome. 
• Differentiate by clarifying history (colitis vs. 
colorectal neoplaia), fecal flotations, 
abdominal imaging, and colonoscopy or 
proctoscopy and biopsy.
• Usually unremarkable; microcytic anemia 
may be present in Boxer dogs with GC 
secondary to intestinal bleeding. • Chemistry 
panel may reveal hypoalbuminemia, 
electrolyte abnormalities, and prerenal 
azotemia in dogs with severe diarrhea and 
anorexia.
IMAGING
Abdominal ultrasound in Boxer dogs with 
GC often reveals mild or moderate mesen-
teric or sublumbar lymphadenomegaly, and 
colonic wall can appear thickened.DIAGNOSTIC PROCEDURES
• Proctoscopy or colonoscopy to obtain 
colonic biopsies. • Most Boxer dogs with 
GC have involvement of descending colon, 
underscoring diagnostic utility of procto -
scopy. • Common changes in appearance to 
colonic wall include erythema, irregularity, 
and ulceration of colonic and rectal wall.
Microbiologic Testing
E. coli  commonly isolated on routine 
bacteriologic media from feces of both healthy 
dogs and dogs with diarrhea; however, 
attempts to isolate E. coli  from colonic 
biopsies is recommended for sensitivity testing 
and optimization of antimicrobial therapy.
• Histopathologic lesions include neutrophilic 
inflammation, epithelial ulceration, crypt 
hyperplasia and distortion, decreased numbers 
of goblet cells, and large numbers of macro -
phages that stain positive with periodic acid–
Schiff (PAS) stain. • Presence of E. coli  within 
macrophages can be confirmed using 
fluorescent in-situ hybridization (FISH).
  TREATMENT
• Outpatient medical management following 
confirmation of diagnosis. • Antimicrobial 
therapy utilizing fluoroquinolones (unless 
resistance is observed) is mainstay of therapy. 
• Diet change to include moderately 
fermentable fiber source can be used in cases 
that do not show complete resolution of 
diarrhea.
Antimicrobials—First-Line Therapy
• Enrofloxacin (10 mg/kg q24h) for minimum 
duration of 6–8 weeks is typically associated 
with rapid resolution of clinical signs and 
resolution of histopathologic abnormalities. 
• Because enrofloxacin resistance has been 
documented in up to 70% of isolates from 
dogs with GC, attempts to isolate E. coli  from 
colonic biopsies before treatment recommended 
such that antimicrobial susceptibility testing 
can be performed. • Antimicrobials that 
penetrate intracellularly, such as fluoroquinolones, 
chloramphenicol, rifampin, or trimethoprim-
sulfonamides, should be preferentially chosen 
for treatment based on results of antimicrobial 
susceptibility testing. • Chloramphenicol, 
trimethoprim-sulfa, clarithromycin, imipenem, 
and meropenem should be considered for cases 
resistant to fluoroquinolones.Anti-inflammatory/Immunosuppressive 
Drugs
• Rarely indicated in dogs with GC, and used 
at anti-inflammatory dose in conjunction 
with appropriate antimicrobial therapy. 
• Diagnosis must be reconsidered if no 
dramatic improvement in clinical signs 
following administration of fluoroquinolone 
therapy, because not all boxers with signs of 
colitis have GC.
Avoid anticholinergics or other motility 
modifiers such as Imodium ® in dogs with 
infectious cause of diarrhea.
  FOLLOW-UP
• Monitor clinical signs, stool consistency 
and frequency, and body weight. • Dogs 
showing favorable response should improve 
within 5 days of starting effective antimicrobial 
therapy.
• Generally good prognosis following 
appropriate antimicrobial therapy. • Increasing 
injudicious administration of fluoroquinolones 
to dogs is increasing resistance of E. coli  to this 
class of antimicrobials, necessitating use of 
alternative antimicrobials in a subset of dogs.
Boxers, French bulldogs, and border collies 
with GC should not be bred.
SEE ALSO
Colitis and Proctitis.
• AIEC = adherent-invasive E. coli . 
• FISH = fluorescent in-situ hybridization. 
• GC = granulomatous colitis. • IBD = 
inflammatory bowel disease. • PAS = 
periodic acid–Schiff.
Craven M, Dogan B, Schukken A, et al. 
Antimicrobial resistance impacts clinical 
outcome of granulomatous colitis in boxer 
dogs. J Vet Intern Med 2010, 24(4):819–824.
Manchester AC, Hill S, Sabation B, et al. 
Association between granulomatous colitis in 
French Bulldogs and invasive Escherichia coli  
and response to fluoroquinolone antimicro -
bials. J Vet Int Med 2013, 27(1):56–61.

304  Blackwell’s Five-Minute Veterinary Consult  
CCompulsive Disorders—Cats
 BASICS
• Compulsive disorders are relatively invariant 
exaggerated behavior patterns, often derived 
from normal behaviors but out of context and 
repetitive, without apparent function; may be 
performed to the exclusion of other normal 
behaviors or to the detriment of the animal.  
• May be a heterogeneous group of conditions 
with differing pathologies including compul -
sive, stereotypic, and neurologic; therefore 
abnormal repetitive behaviors might be used 
to describe the clinical presentation. • Considered 
here are psychogenic dermatitis/alopecia, 
compulsive fabric chewing/sucking, and 
hyperesthesia syndrome.
• Diagnosis of exclusion; must rule out 
pathophysiologic causes, including psycho-
motor seizures, before a presumptive 
diagnosis is made. • Can be a behavioral 
response to confinement, specific anxiety-
producing event, or undefined environmental 
conditions (e.g., conflict, stress, anxiety, 
frustration); over time, can become fixed and 
independent of the environment; affected cats 
may lack control of onset or termination.  
• Behaviors may be self-reinforcing—allowing 
some animals to cope with conditions that do 
not meet their species-specific needs.
• Behavioral. • Gastrointestinal—fabric 
chewing/sucking. • Musculoskeletal—feline 
hyperesthesia (involves cutaneous trunci 
muscle), tail attack/mutilation. • Skin/
exocrine—psychogenic dermatitis/alopecia.  
• Nervous—feline hyperesthesia syndrome.
GENETICS
None identified, although the association of 
compulsive fabric chewing/sucking with 
Asian breeds suggests a heritable component.
Unknown, uncommon.
Species
Cat
Breed Predispositions
Siamese, Burmese, Birman, and crosses may 
be overrepresented for fabric chewing and 
sucking.
• Compulsive disorders can develop at any 
time, generally not seen in kittens.  
• Psychogenic dermatitis/alopecia—6 months 
to 12 years. • Fabric chewing/sucking—12–49 
months; generally around 24 months. • Hyper  - 
esthesia syndrome—1–5 years.
NoneSIGNS
• Behaviors may quickly increase in frequency if 
reinforced with attention by owner. • Scolding 
or punishment may increase cat anxiety and 
stress and worsen expression of behavior.
• Onset may be coincident with environmen-
tal change (e.g., move or new household 
member) suggesting stress effect; cat may hide 
to avoid punishment. • Psychogenic dermatitis/
alopecia—may be associated with excessive 
grooming to exclusion of other activities; may 
be history of flea exposure or diet change. • 
Compulsive fabric chewing/sucking—some 
patients show preference for specific fabric 
type such as wool or may have general texture 
preference; grind fabric with molars; may 
ingest fabric leading to foreign body 
obstruction. • Hyperesthesia syndrome—  
may be triggered by tactile contact (petting 
along dorsum and rump); may be episodic; 
flea exposure.
• Psychogenic dermatitis/alopecia—focal, 
partial, and bilateral dermatitis or alopecia; 
most common locations: groin, ventrum, and 
medial or caudal thigh regions; appearance of 
skin variable (normal or abnormal; erythe  matous 
to abraded). • Fabric chewing/sucking—  
often normal; secondary gastrointestinal 
inflammation or obstruction may occur if cat 
ingests material. • Hyperesthesia syndrome—
episode may be prompted by petting or 
scratching dorsum; signs may include dilated 
pupils, salivation, alarming vocalization, 
“rippling skin” (hyperresponsive cutaneous 
trunci muscle), inappropriate urination or 
defecation, tail twitching, frantic grooming, 
self-directed (especially to tail) or owner-
directed aggression, escape behavior.
CAUSES
Unidentified
• Changes in environment might predispose 
cat to compulsive disorder. • More commonly 
reported in indoor cats. • Cats fed ad libitum 
may have lower prevalence of fabric chewing/
sucking; must be balanced with nutritional 
needs.
 DIAGNOSIS
Rule out medical, including psychomotor 
seizures, before behavioral diagnosis is made.
Psychogenic Dermatitis/Alopecia
• Skin conditions—especially if associated 
with pruritus including external parasites; 
hypersensitivity to parasites, fleas, or food; 
atopy; neoplasia; fungal or bacterial dermatitis. 
• Nervous system disorders. • Disk rupture and associated neuritis. • Feline hyperesthesia 
syndrome. • Pain/neuropathy.
Fabric Chewing/Sucking
• Lead intoxication. • Hyperthyroidism.  
• Thiamin deficiency. • Gastrointestinal upset.
Hyperesthesia Syndrome
• Seizure disorder. • Skin disorders including 
external parasites, hypersensitivity to food, 
flea bites, and parasites; atopy. • Spinal 
disorder/neuropathy. • Myositis, myopathy.
Minimum database to rule out metabolic 
abnormalities. No consistent clinicopatholo-
gies associated with compulsive disorders.
Psychogenic Alopecia
Microscopic examination of hairs (tricho-
gram), skin scraping, skin biopsy, fungal 
culture, bacterial culture, examination for 
external parasites, exclusion diet to rule out 
dermatologic condition.
Fabric Chewing
• Serum lead level—if indicated for pica.  
• Serum T4.
Rule out dermatologic conditions as above.
IMAGING
• CT or MRI—if indicated by abnormalities 
on examination, i.e., to diagnose neurologic, 
pain. • Fabric chewing/sucking—imaging 
gastrointestinal tract if obstruction or foreign 
body suspected.
Complete dermatologic evaluation.
Skin and/or muscle biopsy (as necessary).
• Microscopic examination of hairs—typically 
shafts are cleanly broken off at variable length 
as a result of trauma from the tongue. • If 
primarily behavioral, results of other 
dermatologic testing will be generally normal.
 TREATMENT
Fabric chewing/sucking—create a “safe place” 
for when the cat is left alone, devoid of fabric 
of the sort favored for chewing.
ACTIVITY
Increase opportunities for play and social 
interactions by providing outlets favored by 
the affected cat. Insure environmental needs 
are fully addressed.

Canine and Feline, Seventh Edition  305
C(continued)  Compulsive Disorders—Cats
DIET
• Fabric chewing —increasing fiber in the diet 
has been suggested. • Presumptive psycho-
genic alopecia—exclusion diet.
• Identify and remove triggers for the behavior, 
if applicable. • Do not reward the behavior.  
• Ignore the behavior as much as possible; 
distract the cat and initiate an acceptable 
behavior. • Note details of the time, place, and 
social milieu so that an alternative behavior 
(play or feeding or food-dispensing toy) may 
be scheduled prior to initiation of the 
compulsive behavior. • Punishment is 
contraindicated and can increase the unpre -
dictability of the patient’s environment, 
increase patient fear or aggressive behavior, and 
disrupt the human–animal bond. • Reduce 
environmental stress—increase the predictabil -
ity of household events (feeding, play, exercise, 
and social time with the client); eliminate 
unpredictable events as much as possible.
N/A unless obstructed.
• If a specific etiology cannot be identified, 
anti-compulsive or anti-anxiety drugs may be 
helpful; relatively high doses may be required 
(Table 1). • Goal—use the drugs until control 
is achieved for 2 months; attempt gradual 
withdrawal by decreasing dosage at 2-week 
intervals; treatment should be resumed at the 
last effective dose at the first sign of relapse; 
may be life-long. • Drugs are listed with 
dosage used to manage behavior and common 
side effects. • Hyperesthesia syndrome—
gabapentin has been reported anecdotally 
to reduce the frequency and intensity of bouts.
(SSRIs)—depending on agent: poor appetite, 
constipation, sedation. • T ricyclic antidepres-
sants (TCAs)—cats with history of cardiac 
conduction disturbances, urinary or fecal 
retention, megacolon, lower urinary tract 
blockages, seizures, and glaucoma.  
• T ransdermal route does not appear to 
consistently produce satisfactory drug levels.PRECAUTIONS
• Start behavioral drugs at low dose to avoid 
side effects; may give at bedtime to reduce 
complaints of sedation; may be given with 
food. • No drugs approved by FDA for 
treatment of these disorders in cats; inform 
client of extra-label use and risks involved; 
document the discussion in the medical 
record or with a release form.
Do not use TCAs or SSRIs with monoamine 
oxidase inhibitors, including selegiline.
• Phenobarbital if seizure disorder suspected. 
• Selegiline if cognitive dysfunction.  
• Presumptive psychogenic alopecia— 
exclusion diet, parasite treatment/preventative, 
trial course of steroids.
 FOLLOW-UP
• Before initiating treatment, record frequency of 
compulsive behavior so that progress can be 
monitored. • Successful treatment requires a 
schedule of follow-up examinations; a 
recommended schedule is a phone check 1 week 
after the initial consultation and an office recheck 
4–6 weeks later; if improvement is evident, the 
treatment regime should be continued; if there is 
no improvement, differential diagnoses should be 
considered or an alternative drug should be 
considered. • If a medication is not effective after 
dosage adjustment, select an agent from another 
drug class.
Create an enriched environment with 
distributed resources, safe and accessible 
elevated resting sites, exercise and play 
opportunities, and predictable social 
interactions with people.
• T reatment failure. • Realistic expectations 
must be created; immediate control of a 
longstanding problem is unlikely.
With treatment, prognosis for improvement 
is good; treatment can be lifelong. MISCELLANEOUS
Avoidance behavior or aggression toward the 
owner—if the owner punishes the patient 
when it exhibits a compulsive behavior.
None
None
• Do not breed animals that display 
compulsive behavior. • TCAs—contraindi-
cated in pregnant animals.
SYNONYMS
• Psychogenic alopecia—barbering, overg-
rooming. • Hyperesthesia syndrome— 
rippling skin disease, neurodermatitis.
SEE ALSO
Compulsive Disorders—Dogs.
https://www.vet.cornell.edu/departments-
centers-and-institutes/cornell-feline-health-
center/health-information/feline-health-topics
Behavior, 2nd ed. Ames, IA: Wiley-Blackwell, 
2018, pp. 391–403, 425–455, 481–492.
Landsberg G. Stereotypic and compulsive 
disorders. In: Landsberg G, Hunthausen W, 
Ackerman L. Behavior Problems of the Dog 
and Cat, 3rd ed. New York: Saunders/
Elsevier, 2013, pp. 163–179.
Tynes VV, Sinn L. Abnormal repetitive 
behaviors in dogs and cats: a guide for 
practitioners. Vet Clin Small Anim Pract 
2014, 44:543–564.
Sherman
Client Education Handout 
availableDrugs and dosages used to manage feline compulsive disorder.
Drug Drug Class Oral Dosage in Cats Frequency Side Effects—Usually Transient
Fluoxetine SSRI 0.5–1.0 mg/kg q24h Decreased appetite, sleepiness
Paroxetine SSRI 0.25–0.50 mg/kg q24h Constipation
Clomipramine TCA 0.25–1.0 mg/kg q24h Sleepiness, urine retention
Amitriptyline TCA 0.25–1.0 mg/kg q24h Sleepiness, urine retention
Gabapentin Anticonvulsant 3–5 mg/kg q12h Sleepiness, sedationTable 1

306  Blackwell’s Five-Minute Veterinary Consult  
CCompulsive Disorders—Dogs
  BASICS
• Heterogeneous group of abnormal repetitive 
behaviors with differing pathologies (compulsive, 
stereotypic, neurologic). • Categorized as 
locomotor (spinning, tail chasing, circling, 
fence running, pacing, light/shadow chasing); 
oral (licking, sucking/mouthing an object/
body part, e.g., flank, tail, limb; pica, excessive 
drinking, “fly biting”); or hallucinatory (“fly 
biting,” hind end checking, freezing, staring), 
with/without vocal and affective responses. 
• Compulsive disorders (CDs) are abnormal, 
repetitive, exaggerated, and/or sustained, 
variable in form and fixated on a goal; they are 
derived from normal maintenance behaviors 
(e.g., grooming, predation, ingestion); 
motivational conflict or frustration appears to 
trigger the behaviors in specific contexts often 
associated with high arousal; with repeated/
sustained conflict, the behavior becomes 
emancipated from the original trigger(s) and 
displayed in diverse contexts; the animal may 
lack control of onset or termination. 
• Stereotypies are repetitive behaviors that are 
unvaried in sequence and have no obvious 
function or purpose; they may arise in 
situations of conflict/frustration related to 
confinement or husbandry practices, when the 
environment lacks sufficient outlets for the 
normal behavior repertoire, and with maternal 
deprivation.
• Alterations in brain neurotransmitter 
functions likely—primarily serotonin; also 
dopamine, glutamate, endorphins; different 
CDs may preferentially involve different 
brain regions. • Abnormal serotonin 
transmission has been identified as a primary 
mechanism by which compulsive disorders 
are induced; stereotypies might be induced by 
dopaminergic stimulation.
• Behavioral—fear, anxiety, aggression. 
• Cardiovascular—tachycardia. • Endocrine/
metabolic— hypothalamic–pituitary–adrenal 
(HPA) axis upregulation. • Gastrointestinal—
inappetence, gastroenteritis, foreign body 
obstruction. • Hemic/lymphatic/immune—
stress leukogram. • Musculoskeletal—weight 
loss, self-injury. • Respiratory—tachypnea. 
• Skin/exocrine—abrasions/wounds/
infections secondary to self-trauma.
GENETICS
• Higher than expected occurrence among 
first-generation relatives (manifestations may 
differ). • Certain breeds overrepresented for 
specific CDs. • Genetic studies implicate 
N-methyl-D-aspartate (NMDA) glutamatergic 
neurotransmission, particularly via neural 
cadherin ( CDH2 ); also serotonergic transmission via the 5-HT3 receptor, as well 
as other aspects of synaptic transmission.
Generally uncommon, although recent 
studies report in up to 16%; more common 
in certain breeds/families.
Species
Dog
Bull terrier—spinning, freezing/”trancing”; 
German shepherd—spinning, tail chasing; 
Great Dane, German shorthaired pointer—
self-directed oral behaviors, fence running, 
hallucinations; Doberman—flank/blanket 
sucking; miniature schnauzer—hind end 
checking; border collie—light/shadow chasing; 
cavalier King Charles spaniel—fly catching.
May be presented at any age; usually develops 
from onset of sexual (6 months) to social 
(12–24 months) maturity; earlier onset (3–6 
months) reported for some CDs.
Some CDs may be more common in males.
SIGNS
• Wide variety of manifestations—behaviors 
may be repetitive or static (e.g., freezing). 
• Signs may not be observed during exam  - 
ination; descriptions may be unclear; video 
aids diagnosis and treatment planning.
• May be other signs of anxiety/concurrent 
behavioral diagnoses (e.g., separation anxiety, 
fears, aggression) and/or a history of stress 
(e.g., inadequate stimulation, punishment, 
change in routine/household). • Behavior may 
first be displayed as play or in situations of 
high arousal/stress; eventually may occur in 
multiple contexts independent of identifiable 
triggers. • Certain repetitive behaviors are 
expressed in situations with little to no external 
stimulation or evidence of arousal (e.g., 
blanket sucking). • May occur whether or not 
the owner is present; if punished, pet may 
avoid detection. • Hallmarks—behavior is 
ritualized, often exaggerated in form, and with 
time increases in frequency, intensity, and 
duration. • Behavior may be difficult/
impossible to interrupt. • Behavior may 
interfere with normal functioning (e.g., eating, 
sleeping, social interactions).
• May be unremarkable. • May see skin 
lesions/injuries related to self-trauma 
(especially tail, forelimbs, distal extremities); 
excessive tooth wear/damage; lameness or 
poor body condition.
CAUSES
No direct cause.RISK FACTORS
• Environmental stress (e.g., kenneling—
spinning), management. • Owner/environmental 
reinforcement of the behavior. • Punishment of 
the behavior further contributing to stress and 
conflict. • Medical disease, pain, neuropathy—
may increase anxiety or may be primary cause. 
• Sensory abnormalities (e.g., visual deficits) may 
contribute.
  DIAGNOSIS
• Dermatologic (e.g., atopy). • Gastrointestinal 
(e.g., inflammatory bowel disease [IBD], 
neoplasia, gastroesophageal reflux). 
• Metabolic/endocrine (e.g., Cushing’s). 
• Neurologic (e.g., seizure focus, forebrain 
neoplasia, neurodegenerative disorder). 
• Orthopedic (e.g., degenerative joint disease 
[DJD]). • Any disorder causing abnormalities 
of sensation such as dysesthesia, paresthesia 
(e.g., sensory neuropathy). • Other problem 
behaviors—displacement/conflict behaviors, 
play and attention seeking, behaviors 
occurring secondary to lack of stimulation or 
due to resource restriction (e.g., water 
restriction—excessive drinking). • Rule out 
physical/medical causes.
• Usually within reference range—use for 
general health screening; prior to drug use. 
• Hematocrit, cholesterol, triglyceride 
increases have been reported.
Specific to differential diagnoses (e.g., 
endoscopy, biopsy, echocardiography).
IMAGING
• For neurologic differentials, CT or MRI to 
rule out structural brain/spinal disease; altered 
brain/gray matter volume/density reported in 
CD. • Radiography, ultrasound if needed to 
rule out underlying physical causes.
History, video clips.
  TREATMENT
Repetitive behaviors may represent a normal 
coping mechanism. If not harmful nor 
interfering with normal functioning, health, 
or human–animal bond, intervention may be 
unnecessary or contraindicated.
• Generally outpatient. • Sedation—stop-gap 
measure; if needed to stop serious self-
mutilation. • T reat associated physical 
conditions (primary or secondary). 
• Combination of environmental 
modification, behavior modification, and

Canine and Feline, Seventh Edition  307
C
pharmacologic treatment. • Pharmacologic 
intervention—implement early; reduction of 
anxiety facilitates behavioral therapy. 
• Environmental modification—reduce stress 
and anxiety; identify and remove sources 
(e.g., triggers) and/or begin desensitization 
and counter-conditioning exercises. 
• Punishment—contraindicated; increases 
anxiety, may worsen behavior and increase 
patient secrecy. • Provide structured, 
consistent interactions, routine, and sufficient 
exercise, enrichment/mental stimulation 
appropriate to species and individual; 
includes interactive play, food puzzles, and 
reward-based training. • Behavior 
modification—teach the patient to relax in a 
variety of settings; also teach a calm, desirable 
behavior incompatible with the stereotypic 
one, coupled to a verbal cue (e.g., for circling, 
teach to lie down with head and neck 
outstretched in response to “Head down”). In 
some cases, a head collar (e.g., Gentle Leader, 
Halti) left on the dog (when the owner is 
home) in the problem contexts may allow the 
owner to use gentle physical guidance along 
with verbal encouragement/cues to interrupt 
the behavior and redirect it more effectively; 
monitor for situation in which behavior 
occurs and preempt it by engaging the pet in 
an incompatible activity; if behavior occurs, 
disrupt immediately, redirect the animal to 
alternative incompatible activity and reward 
(with food/play/other reinforcer); dogs with 
CD may be more perseverant and thus not 
respond well to extinction procedures. • Have 
clients monitor behaviors via videos and 
written logs (e.g., rate severity) for objective 
assessment of response to therapy; improve -
ment may be seen in frequency and/or 
intensity. • Bandages, collars, braces, and 
crates increase distress, do not address the 
behavioral condition, and may worsen it; if 
needed to ensure healing, use as briefly as 
possible.
ACTIVITY
Environmental enrichment.
• Cure unlikely; usually requires lifelong 
management. • Teach client to recognize all 
body language/behaviors reflecting anxiety.
Tail/limb mutilation—avoid amputation 
unless medically indicated; will not resolve 
the CD.
(SSRIs) and tricyclic antidepressants (TCAs)—  
CNS serotonin effects. • Generally treat at low end of dose range for 4–6 weeks; 
gradually increase dosage if ineffective and no 
adverse events. • SSRIs—fluoxetine 1–2 mg/
kg q24h; sertraline 1–3 mg/kg q24h; 
paroxetine 1–2 mg/kg q24h. • TCAs—
clomipramine is most serotonergic (most 
effective, fewest side effects): 2–3 mg/kg 
q12h. • If symptoms resolve, continue 
medication for >1 month; taper dose no 
faster than 25% every two weeks; recurrence 
common.
• Hepatic or renal compromise—medications 
metabolized by these organs. • Cardiac 
conduction anomalies—TCAs. • Use extreme 
care combining serotonergic drugs (e.g., SSRI 
with tramadol); risk of serotonin syndrome. 
• Do not use SSRIs or TCAs within 2 weeks 
of monoamine oxidase (MAO) inhibitors 
(e.g., selegiline, amitraz).
• Use of listed medications for CD is extra- 
or off-label. • TCA overdose—cardiac 
conduction disturbances. • TCA/SSRI 
overdose—serotonin syndrome. • Side effects 
of SSRIs and TCAs—most common: 
lethargy, appetite change; less common: 
increased anxiety/reactivity, vomiting/
diarrhea; severe side effects may necessitate 
discontinuation.
SSRIs competitively inhibit cytochrome P450 
enzymes: may increase warfarin, many TCAs, 
some benzodiazepines and anticonvulsants, 
other medications; check compatibility and 
adjust dosage if necessary.
• Synthetic pheromones (Adaptil), l-theanine, 
or alpha-casozepine—may reduce anxiety. 
• Adjunctive use of memantine (NMDA 
receptor antagonist) 0.3–1 mg/kg q12h; 
second-line TCAs, e.g., amitriptyline 1–6 mg/
kg q12h. • Selegiline (MAO inhibitor) 
0.5–1 mg/kg q24h—may be effective in some 
cases. • Narcotic antagonists (e.g., naltrexone, 
naloxone)—may be effective but not a practical 
therapeutic option. • Antipsychotics (e.g., 
thioridazine, haloperidol)—not recommended: 
risk of adverse effects, efficacy undocumented.
  FOLLOW-UP
• CBC, biochemistry, T4 (TCAs may 
artificially lower), and urinalysis—semi-
annually to yearly if chronic treatment; adjust 
dosages accordingly. • Medications may take 
8–12 weeks or longer to affect CDs; first sign 
of efficacy may be reduced duration/
frequency. • Relapses common during 
stressful situations; manage with increased intensity of behavior modification, addition 
of short-term, shorter-acting anxiolytics  
(e.g., benzodiazepines).
Monitor for affected relatives; early recogni-
tion and intervention.
Dermatologic/musculoskeletal injury; 
gastrointestinal disorders.
• Untreated CDs almost always progress. 
• >50% reduction in CD in approximately 
two-thirds of cases with appropriate medication 
and behavioral and environmental modification.
Various; specific to type of CD.
• Listed medications not evaluated/
contraindicated in pregnant animals; avoid 
use. • Do not breed affected animals.
SYNONYMS
Obsessive-compulsive disorder.
SEE ALSO
Acral Lick Dermatitis.
• CD = compulsive disorder. • DJD = 
degenerative joint disease. • HPA = 
hypothalamic–pituitary–adrenal. • IBD = 
inflammatory bowel disease. • MAO = 
monoamine oxidase. • NMDA = N-methyl-
D-aspartate. • SSRI = selective serotonin 
reuptake inhibitor. • TCA = tricyclic 
antidepressant.
Hoboken, NJ: Wiley, 2019.
Overall KL, Dunham AE. Clinical features 
and outcome in dogs and cats with 
obsessive-compulsive disorder; 126 cases 
(1989–2000). J Am Vet Med Assoc 2002, 
221:1445–1452.
Author  Mary P . Klinck
Karen L. Overall
available online(continued)  Compulsive Disorders—Dogs

308  Blackwell’s Five-Minute Veterinary Consult  
CCongenital and Developmental Renal Diseases
 BASICS
• Functional or morphologic abnormalities 
resulting from heritable (genetic) or acquired 
disease processes affecting differentiation and 
growth of the developing kidney. • Renal 
agenesis—complete absence of one or both 
kidneys. • Renal dysplasia—disorganized renal 
parenchymal development. • Renal ectopia—
congenital malposition of one or both 
kidneys. • Glomerulopathy—glomerular 
disease of any type. • Polycystic renal 
disease—formation of multiple, variable-sized 
cysts throughout the renal medulla and cortex. 
• Renal telangiectasia—multifocal vascular 
malformations involving the kidneys and 
other organs. • Renal amyloidosis—extracel -
lular deposition of amyloid in glomerular 
capillaries, glomeruli, and interstitium.  
• Nephroblastoma—congenital renal 
neoplasm arising from the pluripotent 
metanephric blastema. • Multifocal renal 
cystadenocarcinoma—hereditary renal 
neoplasm in dogs. • Fanconi syndrome—  
generalized renal tubular functional anomaly 
characterized by impaired reabsorption of 
glucose, phosphate, electrolytes, amino acids, 
and uric acid. • Primary renal glucosuria—
defect in renal tubular reabsorption of glucose. 
• Cystinuria—excessive urinary excretion of 
cystine due to defect in renal tubular 
reabsorption of cystine and other amino acids. 
• Xanthinuria—excessive urinary excretion of 
xanthine caused by a deficiency in xanthine 
oxidase. • Hyperuricuria—excessive urinary 
excretion of uric acid, sodium urate, or 
ammonium urate. • Primary hyperoxaluria—
intermittent hyperoxaluria, l-glyceric aciduria, 
and oxalate nephropathy. • Congenital 
nephrogenic diabetes insipidus—polyuria 
caused by diminished renal responsiveness to 
antidiuretic hormone.
Many congenital and developmental renal 
disorders are caused by genetic abnormalities 
that disrupt the normal development and 
interaction of multiple embryonic tissues 
involved in formation of the mature kidney. 
Nongenetic factors are also possible.
Renal/urologic.
GENETICS
• Familial renal disorders have been reported 
in the following breeds: ◦ Renal agenesis—
beagle, Doberman pinscher, Shetland 
sheepdog. ◦ Renal dysplasia—Alaskan 
Malamute, border terrier, boxer, bullmastiff, 
bulldog, Cairn terrier, cavalier King Charles 
spaniel, chow chow, cocker spaniel, Dutch 
kookier, golden retriever, Finnish harrier, keeshond, Lhasa apso, miniature schnauzer, 
Norwegian elkhound, Rhodesian ridgeback, 
shih tzu, soft-coated wheaten terrier, standard 
poodle. ◦ Glomerulopathy—Airedale terrier, 
beagle, Belgian shepherd, Bernese mountain 
dog, Brittany spaniel, bull terrier, bullmastiff, 
Dalmatian, Doberman pinscher, English 
cocker spaniel, Newfoundland, Pembroke 
Welsh corgi, Rottweiler, Samoyed, soft-coated 
wheaten terrier. ◦ Polycystic renal disease—
beagle, bull terrier, Cairn terrier, West 
Highland white terrier; Persian, exotic 
shorthair, Himalayan, British blue cats.  
◦ Renal telangiectasia—Pembroke Welsh 
corgi. ◦ Renal amyloidosis—Abyssinian, 
oriental shorthair, Siamese cats; beagle, 
English foxhound, shar-pei. ◦ Renal cystad -
enocarcinoma—German shepherd. ◦ Fanconi 
syndrome—basenji and border terrier.  
◦ Primary renal glucosuria—Norwegian 
elkhound, Scottish terrier, basenji.  
◦ Cystinuria—American pit bull terrier, basset 
hound, English bulldog, dachshund, mastiff, 
Newfoundland, Rottweiler, among others.  
◦ Xanthinuria—cavalier King Charles spaniel, 
wirehaired dachshund; domestic shorthair 
cats. ◦ Hyperuricuria—Dalmatian, black 
Russian terrier, English bulldog. ◦ Primary 
hyperoxaluria—domestic shorthair cats; 
Tibetan spaniel.
Uncommonly recognized, but occur more 
frequently in related animals from more than 
one generation than in the general popu  - 
lation.
Species
Sporadic cases can occur without apparent 
familial predisposition in any breed of dog or cat.
Most are <5 years old at time of diagnosis.
• Familial cystinuria occurs primarily in male 
dogs. • Samoyed hereditary glomerulopathy 
more common in males. • Familial glomeru-
lonephropathy of Bernese mountain dogs is 
more common in females.
SIGNS
Most congenital and developmental disorders 
cannot be distinguished from acquired renal 
disease without kidney biopsy.
• Indicate chronic kidney disease. • Some 
glomerulopathies associated with abdominal 
distension, edema, or other signs of nephrotic 
syndrome. • Abdominal distension in some 
patients with polycystic kidneys or renal 
neoplasms. • Hematuria or abdominal pain in some patients with renal telangiectasia or 
renal neoplasms. • Patients with unilateral 
renal agenesis, ectopic kidneys, and isolated 
renal tubular transport defects are frequently 
• Signs associated with advanced chronic 
kidney disease. • Ascites or pitting edema in 
some patients with protein-losing glomeru-
lopathies or amyloidosis. • Renomegaly or 
abdominal mass lesions in some patients with 
polycystic kidneys, renal neoplasms, or fused 
ectopic kidneys.
CAUSES
Nonhereditary
• Infectious agents—feline panleukopenia 
virus and canine herpesvirus infection 
associated with renal dysplasia. • Drugs— 
corticosteroids, diphenylamine, and biphenyls 
associated with polycystic kidneys; chloram-
bucil and sodium arsenate associated with 
renal agenesis. • Dietary factors—hypo- or 
hypervitaminosis A associated with renal 
ectopia.
 DIAGNOSIS
• Rule out acquired and nondevelopmental 
causes of primary renal disease. • Rule out 
nonrenal causes of hematuria, proteinuria, 
glucosuria, abdominal distention, or ascites.
• Nonregenerative anemia. • Azotemia and 
urine specific gravity <1.030 in dogs and 
<1.035 in cats. • Proteinuria, hypoalbumine-
mia, and hypercholesterolemia with nephrotic 
syndrome. • Normoglycemic glucosuria in 
Fanconi syndrome or primary renal glucosuria. 
• Hematuria with congenital renal neoplasia 
or renal telangiectasia. • Cystine crystalluria 
with cystinuria. • Xanthine crystalluria with 
xanthinuria. • Urate crystalluria with hyper  - 
uricuria.
Genetic tests are available for some specific 
genetic mutations associated with hereditary 
renal disorders.
IMAGING
Survey abdominal radiography, renal ultra  - 
sonography, and excretory urography may 
identify and characterize congenital and 
developmental renal disorders and their 
associated sequelae.
Consider light microscopic evaluation of 
kidney biopsy specimens from patients with 
morphologic or functional abnormalities of 
the kidney for which a definitive diagnosis 
has not been established.

Canine and Feline, Seventh Edition  309
C(continued)  Congenital and Developmental Renal Diseases
• Renal dysplasia—primary lesions include 
immature glomeruli, persistent mesenchyme, 
persistent metanephric ducts, atypical 
tubular epithelium, and dysontogenic 
metaplasia; primary lesions usually associ -
ated with, and may be obscured by, 
secondary degenerative, inflammatory, and 
compensatory lesions. • Glomerulopathies—
usually normal-to-small kidneys; most are 
characterized by a primary membranoprolif -
erative glomerulonephritis with variable 
degrees of tubulointerstitial disease, others 
have cystic atrophic membranous glomeru -
lopathy. • Polycystic renal disease—see 
Polycystic Kidney Disease. • Renal amyloidosis—
see Amyloidosis. • Renal telangiectasia—  
multiple, variable-sized, red-black, blood-filled 
nodules and clots in the renal cortex and 
medulla, interstitial fibrosis, interstitial 
mononuclear cell infiltrate, and hydronephrosis. 
• Nephroblastoma—unilateral renal mass; 
contains both embryonic mesenchymal and 
epithelial tissue components. • Multifocal 
renal cystadenocarcinoma—bilaterally 
enlarged kidneys with irregular protruding 
cystic structures or multifocal neoplastic 
renal tubular epithelial cell proliferations. • 
Renal ectopia—kidneys abnormally located 
in the retroperitoneal space or abdomen; 
horseshoe kidneys are symmetrically fused 
along the medial border of either pole. • 
Fanconi syndrome—  
inconsistent findings of tubular atrophy, 
interstitial fibrosis, and acute papillary necrosis. 
• Primary hyperoxaluria—large, irregularly 
shaped kidneys; renal tubular deposition of 
calcium oxalate crystals and variable interstitial 
and periglomerular fibrosis.
 TREATMENT
• Congenital and developmental renal 
disorders often have no specific treatment.  
• Supportive strategies are similar to those for 
acquired chronic kidney disease and may 
improve quality of life and minimize 
progression in patients with renal dysfunction. • Refer to chapters describing specific renal 
diseases or clinical syndromes.
Refer to chapters describing specific renal 
Avoid potentially nephrotoxic drugs or 
anesthetic agents that decrease renal function.
Avoid drugs requiring renal excretion in 
patients with renal failure; if necessary, 
modify dosage regimens to compensate for 
decreased renal clearance of drugs and other 
metabolites.
 FOLLOW-UP
Congenital and developmental renal disorders 
are irreversible, so control lies in preventing 
breeding of affected animals.
• Acute or chronic renal failure. • Nephrotic 
syndrome. • Urolithiasis. • Hydronephrosis.  
• Urinary tract infection.
• Highly variable; depends on the specific 
disorder, the extent of primary lesions, and 
the severity of renal dysfunction. • Congenital 
and developmental disorders are irreversible 
and may result in advanced chronic kidney 
disease; some patients with mild to moderate 
renal dysfunction may remain stable for long 
periods. • Patients with some disorders may 
remain asymptomatic unless the disorder is 
complicated by urolithiasis, infection, or 
other disease processes that promote 
progressive renal dysfunction. MISCELLANEOUS
• Polycystic renal disease associated with 
hepatic biliary cysts. • Cystinuria, xanthinu-
ria, and hyperuricuria associated with 
formation of uroliths. • Amyloidosis in 
Chinese Shar-Pei dogs associated with 
intermittent pyrexia or swelling of the hocks. 
• Renal neoplasms associated with hyper-
trophic osteoarthropathy, polycythemia, or 
other paraneoplastic syndromes.
SYNONYMS
• Familial renal disease. • Juvenile renal 
disease.
SEE ALSO
• Amyloidosis.
• Fanconi Syndrome.
• Oliguria and Anuria.
• Renal T ubular Acidosis.
• Urolithiasis, Cystine.
Segev G. Familial and congenital renal 
diseases of cats and dogs. In: Ettinger SJ, 
Feldman EC, Cote E, eds., Textbook of 
Veterinary Internal Medicine, 8th ed.  
St. Louis, MO: Elsevier, 2017, pp. 1981–1984.
Author  John M. Kruger
of Carl A. Osborne, and Scott D. Fitzgerald.

310  Blackwell’s Five-Minute Veterinary Consult  
CCongenital Ocular Anomalies
  BASICS
Solitary or multiple abnormalities that affect 
the globe or its adnexa; observed in dogs and 
cats at birth or within the first 6–8 weeks of 
life.
• Breed-related inherited defects.
• Spontaneous malformations.
• In utero systemic infections and inflamm -
ations, exposure to toxic compounds, and 
lack of specific nutrients in pregnant dams or 
bitches.
Ophthalmic—entire eye or any part; unilateral 
or bilateral.
GENETICS
• * Indicates availability of genetic testing for 
all or most affected breeds.
• Congenital keratoconjunctivitis sicca 
(KCS) and KCS ichthyosiform dermatosis 
(KCSID)*—cavalier King Charles spaniel 
(dry eye and curly coat syndrome): 
recessive trait.
• Persistent pupillary membranes (PPM)—
Basenji and other breeds: unknown mode of 
• Persistent hyperplastic tunica vasculosa 
lentis (PHTVL) and persistent hyperplastic 
primary vitreous (PHPV)—Doberman 
pinscher and Staffordshire bull terrier: 
dominant allele with variable expression.
• Retinal dysplasia—English springer spaniel: 
recessive trait.
• Collie eye abnormality (CEA)*—collie and 
other dog breeds: recessive trait.
• Merle ocular dysgenesis (MOD)—
Australian shepherd: autosomal recessive trait 
with incomplete penetrance.
• Oculo-skeletal dysplasia (OSD)*—
Labrador retriever and Samoyed: autosomal 
dominant trait with incomplete penetrance.
• Retinal dystrophy*—Briard: recessive trait.
• Rod cone dysplasia*—collies, Irish setter, 
Cardigan Welsh corgi, sloughi: recessive traits; 
nonallelic disease.
• Early retinal degeneration*—Norwegian 
elkhound: recessive trait.
• Photoreceptor dysplasia—Belgian shepherd.
• Cone rod dystrophy*—American pit bull 
terrier, American Staffordshire terrier, springer 
spaniel, long-, short- and wirehaired 
dachshunds: recessive traits; nonallelic disease.
• Cone degeneration, achromatopsia, or day 
blindness*—Alaskan Malamute, Australian 
shepherd, German shepherd dog, miniature 
American shepherd, German shorthaired 
pointer, Australian cobberdog, Labrador 
retriever and Labrador crosses (incl. 
Labradoodles): recessive traits.• Optic nerve hypoplasia—miniature and toy 
poodle, sporadically in other breeds: unknown 
mode of inheritance.
• Photoreceptor dysplasia*—Abyssinian, 
Somali, and Ocicat cat breeds: dominant 
trait.
• Incidence—low; dogs > cats.
• CEA— >50% in collies, lower in other 
breeds.
Species
SIGNS
• Depends on defect.
• May cause no signs of disease; often 
incidental finding.
• May be congenitally blinding disease.
Ranges from none to severe visual impair-
ment to blindness.
• Anophthalmos—congenital lack of globe; rare.
• Microphthalmos—congenitally small eye; 
often associated with other hereditary defects, 
including MOD.
• Eyelid agenesis or colobomas of eyelids in 
cats—result in congenitally open eyelids; 
affects temporal portion of upper eyelid; may 
cause blepharospasm, epiphora, and corneal 
changes as result of trichiasis.
• Dermoids—islands of aberrant skin tissue 
involving either eyelids, conjunctiva, or 
cornea; may cause blepharospasm and 
epiphora (see Web Figure 1).
• Atresia and imperforate puncta of lacrimal 
system, common in dogs—results in tear 
streak at nasal canthus.
• Congenital KCS—usually unilateral; 
affected eye appears smaller; thick mucous 
discharge from red and irritated eye.
• KCSID—therapy-resistant KCS, curly coat 
and progressive dermatologic signs, including 
footpad hyperkeratosis that can cause 
lameness.
• PPMs—remnants of pupillary membrane 
spanning from iris collarette to another 
portion of iris, lens, or cornea; may coexist 
with other defects (see Web Figures 2 and 3).
• Iris cysts—pigmented or nonpigmented 
spherical structures may float freely in 
anterior chamber or be attached to posterior 
iris, ciliary body, or corneal endothelium (see 
Web Figure 4).
• Congenital glaucoma—rare; buphthalmic 
eye, often associated with multiple anterior 
segment changes.• Pupillary abnormalities—polycoria, acorea, 
aniridia, or dyscoria.
• Congenital cataracts—primary, inherited, 
or developmental defect; associated with 
anomalies of lens, including microphakia, 
lenticonus or lentiglobus, and coloboma (see 
Web Figures 5 and 6).
• PHTVL and PHPV—persistence of parts 
of hyaloid vasculature; developmental 
aberrations of vitreous, lens, and lens capsule; 
may show leukocoria as result of retrolental 
fibrovascular plaques and/or cataracts, or 
reddish sheen from pupillary area with 
intralenticular bleeding.
• Retinal dysplasia—effect on retinal 
structure depends on severity; ranges from 
focal neuroretinal folds (multifocal defects 
often along major blood vessels in central 
tapetal fundus) to geographic dysplasia 
(abnormal central tapetal fundus area with 
elevated retina and surrounding hyperpig -
mentation and scarring) to complete retinal 
• CEA—bilateral area of choroidal 
hypoplasia temporal to optic nerve head: 
focal increased visibility of white sclera and 
scarce, irregularly shaped choroidal blood 
vessels; visual impairment or blindness can 
be caused by optic nerve coloboma and 
• MOD—microphthalmia, microcornea, 
heterochromia irides, pupillary abnormalities, 
cataract, fundus coloboma, retinal 
detachment, intraocular hemorrhage.
• Coloboma of posterior segment—primary 
or in conjunction with CEA or MOD; 
focal, well-defined tissue depression, 
typically at 6 o’clock position in optic nerve 
head in CEA, or in fundus periphery in 
MOD; may be in other locations of fundus 
near optic nerve head.
• OSD—heterozygous carriers typically 
display signs of focal/multifocal retinal 
dysplasia, whereas homozygous animals 
display complete phenotype, including 
skeletal (short-limbed dwarfism) and ocular 
defects (ranging from retinal dysplasia to 
retinal detachments; corneal and lens 
opacities also possible).
• Retinal dystrophy—congenital night 
blindness, variable severity and progression of 
day blindness.
• Rod cone dysplasia, early retinal degeneration, 
photoreceptor dysplasia, and cone rod 
dystrophy—pupillary abnormalities and 
visual impairment in first few months of life; 
disease progression depends on specific 
disease and breed affected.
• Cone degeneration—apparent day blind  ness 
from 8–10 weeks of age; vision in dim light 
never affected.
• Retinal detachment—often in conjunction 
with other hereditary ocular diseases; signs 
depend on extent of detachment and include 
widely dilated pupils, weak to absent

Canine and Feline, Seventh Edition  311
C
pupillary light reflexes; presence of fundus 
areas that appear out of focus, vascularized 
membranous structure (retina) visible within 
pupillary aperture behind lens, blindness with 
complete bilateral detachment.
• Optic nerve hypoplasia—avascular, dark, 
abnormally small, circular optic nerve head, 
may result in blindness.
CAUSES
• Genetic.
• Infections or inflammation during pregnancy.
• Toxicity during pregnancy.
• Nutritional deficiencies.
Breeding dogs or cats that are homozygous or 
heterozygous for hereditary disease with 
recessive inheritance, or affected animals 
where disease has dominant inheritance.
  DIAGNOSIS
• Infectious and inflammatory processes in 
adnexa—may mimic and mask congenital 
• Cataracts induced at early age may be 
interpreted as congenital.
• Postinflammatory ophthalmic lesions with 
anterior or posterior synechia—easily confused 
with iris to cornea or iris to lens PPMs.
• T umors of anterior segment may be 
confused with iris cysts.
• Focal, multifocal, or generalized retino  - 
pathy of inflammatory origin—resulting 
retinal atrophy may appear to be retinal 
dysplasia or photoreceptor dysplasia.
• Retinal detachment as result of trauma or 
uveitis in young dogs.
• Optic nerve atrophy due to inflammatory 
process may be difficult to differentiate from 
congenital optic nerve hypoplasia.
IMAGING
• Routine ophthalmic ultrasound—use of 
10–20 MHz probes for evaluation of 
intraocular changes in case of opacities that 
prevent proper ophthalmic examination.
• High-resolution ultrasound—use of 
20–50 MHz probes for evaluation and 
measurement of corneal and anterior chamber 
structures, e.g., anterior chamber cysts or 
• Examination with diffuse and focal 
illumination, including slit-lamp biomicro -
scopy—evaluation of adnexal and anterior 
segment anomalies, including lens and 
anterior vitreous (following pharmacologic 
pupil dilation).
• Schirmer tear test—evaluate tear 
production.• Tonometry—when glaucoma or uveitis 
• Direct and/or indirect ophthalmoscopy—
evaluation of posterior segment anomalies; 
pharmacologic pupil dilation necessary; 
difficult to perform in patients with opacities 
in cornea, anterior chamber, lens, or anterior 
vitreous.
• Gonioscopy—evaluation of width of and 
presence of signs of dysgenesis in iridocorneal 
angle when glaucoma suspected; critical to 
include examination of unaffected eye.
• Electroretinography (ERG).
• Optical coherence tomography (OCT).
• Referral to ophthalmologist necessary for 
gonioscopic, ERG, and OCT examinations.
  TREATMENT
• Patients usually referred to ophthalmologist.
• No treatment for most congenital 
abnormalities, except symptomatic treatment 
or surgery.
• In KCS—removing discharge and flushing 
with saline.
• Accommodate handicap of blind animals—
leash walking, supervision.
ACTIVITY
Visually impaired or blind animals need 
adequate exercise.
DIET
Provide diet adequate in vitamins, antioxi-
dants, and omega-3 fatty acids, especially in 
photoreceptor degenerations.
Discuss visual capacity, possible progression, 
and sequelae.
• Adnexal abnormalities—surgery as soon as 
possible.
• Congenital KCS—parotid duct trans- 
position.
• Cataract extraction—congenital cataract 
may be associated with other anomalies, 
decreasing chances for visual rehabilitation or 
causing surgical complications; presurgical 
evaluation should include imaging and ERG.
• Congenital glaucoma—surgical options 
depend on presence of vision, size of patient/
eye, and level of motivation of owners; 
enucleation or intrascleral prosthesis typical 
treatments of choice; consider euthanasia if 
• Barrier retinopexy to prevent occurrence of 
retinal detachments with large colobomatous 
or dysplastic lesions of fundus—carries risk of 
inducing retinal detachment.  MEDICATIONS
• Congenital KCS—frequent application of 
tear substitutes; antibiotics may be added; 
cyclosporine ophthalmic ointment q12h.
• Congenital cataracts—if only in nuclear 
region of lens, mydriatics used to increase 
visual capability.
  FOLLOW-UP
• Congenital KCS—repeated monitoring of 
tear production and status of external eye.
• Congenital cataracts and severe PHTVL 
and PHPV—regular checkups, usually on 
6-month basis; monitor progression.
• Large colobomatous defects of the fundus 
and geographic retinal dysplasia—regular 
checkups to monitor possible retinal 
Restrict breeding of affected animals and of 
known carriers of hereditary defects; DNA-
based tests available for various diseases (see 
Internet Resources).
• In congenital KCS with parotid duct 
transposition, keratitis and dermatitis may 
occur due to excessive deposition of minerals 
from saliva.
• Cataract surgery can result in glaucoma, 
retinal detachment, and corneal scarring in 
puppies and kittens; surgery seldom 
recommended before age 8–12 weeks.
• Most abnormalities affecting adnexa can be 
corrected in young dogs and cats.
• Prognosis for most anterior segment 
abnormalities good to fair.
• Prognosis for glaucoma poor.
• For photoreceptor abnormalities prognosis 
for vision poor, but eyes should remain 
comfortable.
• For most other abnormalities prognosis 
depends on severity of condition.
• Dogs and cats affected with congenital 
ocular anomalies resulting in blindness and/or 
pain should not be used for breeding.
• Many congenital ocular anomalies are 
hereditary and use of affected animals in 
breeding should be prohibited or severely (continued)  Congenital Ocular Anomalies

312  Blackwell’s Five-Minute Veterinary Consult  
Crestricted. Breeding advice should be sought 
from kennel club and breed associations.
• CEA = collie eye anomaly.
• ERG = electroretinography.
• KCSID = KCS ichthyosiform dermatosis.
• MOD = merle ocular dysgenesis.
• OSD = oculo-skeletal dysplasia.
• PHPV = persistent hyperplastic primary 
vitreous.
• PHTVL = persistent hyperplastic tunica 
vasculosa lentis.
• PPM = persistent pupillary membrane.
• These laboratories offer DNA-based tests:
◦ www.antagene.com◦ www.CatDNAtest.org
◦ www.aht.org.uk
◦ www.laboklin.co.uk
◦ https://breeder.wisdompanel.com/
◦ https://vgl.ucdavis.edu/services
◦ www.vetgen.com
◦ www.caninegeneticdiseases.net
◦ www.optimal-selection.com
◦ www.mydogdna.com
◦ www.pawprintgenetics.com
◦ https://www.vet.upenn.edu/research/
academic-departments/clinical-sciences-
advanced-medicine/research-labs-centers/
penngen/penngen-tests
• Good summaries of genetic basis and 
clinical signs of diseases, relevance of test 
results, and relevant references are listed on 
most of these websites. Suggested Reading
Gelatt KN, Gilger BC, Kern TJ, ed. 
Veterinary Ophthalmology, 5th ed. Ames, 
IA: Wiley-Blackwell, 2013.
Maggs DJ, Miller PE, Ofri R, ed. Slatter’s 
Fundamentals of Veterinary 
Saunders, 2017.
Author  Simon A. Pot
available onlineCongenital Ocular Anomalies  (continued)

Canine and Feline, Seventh Edition  313
C
 BASICS
Anomalous development of spinal structures, 
which are apparent at birth or within the first 
weeks of life.
• Malformation of the occipital bones, atlas, 
and axis; malformation of the odontoid 
process; occipitoatlantoaxial malformation; 
and occipital dysplasia—may cause atlanto-
axial subluxation with secondary compression 
and trauma to the first segments of the 
cervical spinal cord.
• Other embryonic or developmental 
anomalies of the vertebrae such as hemiverte-
bra, transitional vertebra, block vertebra, and 
butterfly vertebra—these defects cause 
deformity and instability of the vertebral 
canal and, on rare occasions, compression of 
the associated spinal cord or nerve roots.
• Sacrococcygeal dysgenesis—characterized 
by absence or partial development of the 
sacrocaudal spinal cord segments; often 
associated with additional malformations 
(e.g., spina bifida).
• Spina bifida—caused by failure of fusion of 
the vertebral arches; may be associated with 
protrusion of the spinal cord and meninges; 
other malformations often linked to this 
syndrome include spinal dysplasia, dysraphism, 
syringomyelia/hydromyelia, and myelodysplasia.
• Congenital spinal stenosis—can occur when 
vertebral malformations cause segmental or 
diffuse narrowing of the spinal cord; inborn 
errors in skeletal growth, hypertrophy of 
ligamentum flavum, and bony proliferation 
may also contribute to the stenosis.
Nervous—spinal cord; spinal nerve roots; and 
vertebral column.
GENETICS
• A genetic background, with unknown 
mode of inheritance, is suspected in most 
congenital spinal diseases.
• Sacrococcygeal dysgenesis—autosomal 
dominant.
• Thoracic hemivertebra of German 
shorthaired pointers—autosomal recessive.
N/A
Species and Breed Predilections
and axis—most common in small-breed dogs.
• Hemivertebra, transitional vertebra, block 
vertebra, and butterfly vertebra—most 
common in brachycephalic, “screw-tailed” 
breeds (e.g., French and English bulldog, pug, 
Boston terrier).• Sacrococcygeal dysgenesis—Manx cat.
• Spina bifida—bulldog, Manx cat, and other 
screw-tailed breeds.
• Spinal dysraphism—Weimaraner.
• Congenital spinal stenosis—Doberman 
pinscher; chondrodystrophic breeds.
• Often silent, vertebral malformation 
may cause clinical disease during the 
rapid growth of the animal (e.g., 5–9 
months of age).
• Spinal cord anomalies cause clinical disease 
from birth on.
SIGNS
• Distortion of the spinal column—lordosis; 
kyphosis; and scoliosis in cases of vertebral 
malformations.
• Ataxia and paresis associated with spinal 
cord compression and trauma.
• Signs vary with spinal cord segment(s) 
involved.
CAUSES
Breed-related inherited defects are suspected 
for most congenital spinal abnormalities, 
although interactions between several genes 
and environmental factors (e.g., teratogenic 
compounds, nutritional deficiencies) are 
likely involved and would explain some of 
these complex pathologic changes.
• Teratogenic compounds.
• Toxins.
• Stress.
  DIAGNOSIS
• Metabolic disease (e.g., storage diseases).
• Nutritional disease (e.g., hypovitaminosis 
and hypervitaminosis A, thiamine 
deficiency).
• Early-onset inflammatory or infectious 
processes (e.g., viral, protozoal, and rarely 
bacterial).
• Toxin exposure (e.g., lead, organophos-
phates, hexachlorophene, organochlorine).
• T rauma.
Usually within normal limits.
N/A
IMAGING
• Survey radiography—to reveal vertebral 
malformation(s) and deviation of the spinal 
column.
• Myelography—to determine the level(s) of 
spinal cord compression; flexed and extended 
views may cause neurologic deterioration if 
instability present.• CT myelography and 3D reconstructed 
imaging—to characterize bony abnormali -
ties and associated spinal cord 
• MRI—sensitive modality to visualize 
abnormalities of spinal cord parenchyma, 
cauda equina, nerve roots, and surrounding 
soft tissues.
Cerebrospinal fluid analysis to rule out 
infectious/inflammatory conditions.
• Multiple congenital malformations—often 
present concomitantly; pathologic changes 
reflect several disease processes.
• Acute compression of the spinal cord 
secondary to congenital malformation(s)—
may result in spinal cord ischemia, hemor-
rhage, ballooning of the myelin sheath at the 
point of compression or trauma, and axonal 
swelling or loss; in chronic spinal cord 
compression, myelin degeneration, astrocyto-
sis, and fibrosis are more prominent; at spinal 
sites, cranial and caudal to the primary injury, 
Wallerian degeneration can be observed in 
ascending or descending pathways, respect  - 
ively.
• Chronic changes—may result from 
vertebral malformations secondary to bony 
proliferation, thickening of the joint capsule, 
hypertrophy of articular processes, and 
thickening of the ligaments surrounding the 
spinal cord.
• Atlantoaxial subluxation—congenital 
aplasia or hypoplasia of the odontoid process 
and surrounding ligaments.
• Occipitoatlantoaxial malformations—
fusion of the atlas to the occipital bone 
(cats) and dorsal angulation of the dens 
(dogs).
• Occipital dysplasia—anomaly of the 
foramen magnum in which the occipital 
bone is incompletely formed and fibrous 
tissue membrane covers the caudal 
cerebellum.
• Sacrococcygeal dysgenesis—caudal vertebral 
aplasia or hypoplasia.
• Spina bifida—incomplete fusion of the 
dorsal vertebral arches where the meninges 
or spinal cord can protrude; most com -
monly seen in the caudal lumbar or sacral 
area; a dimple can be observed in a few 
cases secondary to the lack of separation 
between the neuroectoderm and other 
ectodermal structures, leaving a small 
attachment between the spinal cord or 
meninges and the skin; often seen with 
myelodysplasia, central canal defects, 
syringomyelia or hydromyelia, and 
abnormal gray-matter differentiation.
• Spinal stenosis—pathologic changes 
observed within the spinal cord are most 
commonly chronic and are caused by focal or 
diffuse narrowing of the spinal canal.Congenital Spinal and Vertebral Malformations

314  Blackwell’s Five-Minute Veterinary Consult  
C
 TREATMENT
• Depends on severity of neurologic deficits.
• Outpatient—if animal is ambulatory.
• Inpatient—if animal is nonambulatory 
or requires emergency surgical treatment 
(e.g., for atlantoaxial subluxation).
• Restricted activity combined with physical 
therapy—may help neurologically disabled 
patients in the postoperative period; a cart 
may be necessary for severely affected 
patients.
• Management of urination—essential for 
cases in which disorders of micturition 
accompany the spinal injury.
ACTIVITY
Restricted, especially if vertebral subluxation 
DIET
Maintaining a lean bodyweight limits stress 
on the spinal column.
• Many congenital vertebral malformations 
are clinically silent.
• Perform a thorough workup when a 
congenial malformation results in neurologic 
• Heritability is suspected; avoid breeding.
• Many neurologically affected dogs and cats 
left untreated are euthanized.
• Early surgical intervention often necessary 
to alleviate compression of the spinal cord 
and prevent further damage.
• In general, surgical decompression is 
required when congenital malformation(s) 
cause narrowing of the spinal canal and 
compression of the spinal cord. In cases of 
chronic or diffuse spinal cord compression, 
improvement following surgery is minimal.
• Atlantoaxial subluxation—surgical ventral 
decompression combined with stabilization of 
the atlantoaxial joint with pins or screws is 
the treatment of choice.
• Spina bifida—meningoceles can be closed 
surgically to prevent leakage of cerebrospinal fluid 
and infections; surgery usually not attempted 
when the spinal cord parenchyma is involved. MEDICATIONS
Corticosteroids may be used in some cases, 
with variable results.
Avoid steroids with concomitant infections.
Steroids may cause ulcerations of the gastro  - 
intestinal tract and inhibit bone growth.
Steroids reduce immune response following 
vaccination.
N/A
 FOLLOW-UP
• Frequent neurologic examinations—to 
monitor the progression of clinical signs in 
developing animals (e.g., every 4–6 weeks).
• Neuroimaging—repeat as needed.
Avoid breeding affected animals.
• Depend on the type and severity of 
neurologic signs. In cases of subluxation of 
the atlantoaxial joint, acute death may occur.
• Acute paralysis can also be seen with 
vertebral subluxation, with further trauma 
and spinal cord compression.
• Implant failure may be observed after 
surgical decompression/stabilization.
• Prognosis varies depending on the type of 
malformation, degree of spinal cord 
compression or injury, and surgical decom-
pression or stabilization techniques.
• Vertebral malformation without compres-
sion of the spinal cord—prognosis is good.
• Atlantoaxial subluxation following surgical 
decompression or stabilization—prognosis is 
fair to good.
• Spinal cord compression treated surgically—
prognosis is fair.• Spina bifida associated with spinal cord 
malformation, chronic neurologic disease 
despite surgical treatment, and lower motor 
neuron incontinence—prognosis is poor.
• Medical treatment usually is insufficient to 
alleviate moderate to severe neurologic signs 
caused by spinal cord compression secondary 
to congenital vertebral malformation(s).
N/A
N/A
N/A
N/A
SEE ALSO
• Ataxia.
• Atlantoaxial Instability.
• Cervical Spondylomyelopathy (Wobbler 
Syndrome).
• Spinal Dysraphism.
4th ed. St Louis, MO: W.B. Saunders, 
2015, pp. 45–77.
Dewey CW, Da Costa RC. Myelopathies: 
disorders of the spinal cord. In: Dewey 
CW & Da Costa RC, ed., Practical Guide 
Ames, IA: John Wiley & Sons, Inc. 2016, 
pp. 361–371, 412–415.  
Summer BA, Cummings JF , de Lahunta A. 
Veterinary Pathology. Philadelphia, PA: 
Mosby-Year Book, 1995, pp. 86–90.
Wyatt S, Gonçalves R, Gutierrez-Quintana & 
al. Outcomes of nonsurgical treatment for 
congenital thoracic vertebral body malfor -
mations in dogs: 13 cases (2009–2016). 
J Am Vet Med Assoc 2016;253:768–773.
Author  Joane M. Parent.
available onlineCongenital Spinal and Vertebral Malformations  (continued)

Canine and Feline, Seventh Edition  315
C
Congestive Heart Failure, Left-Sided
  BASICS
Failure of the left side of the heart to advance 
blood at a sufficient rate to meet the metabolic 
needs of the patient or to prevent blood from 
pooling within the pulmonary venous circulation.
• Low cardiac output causes lethargy, exercise 
intolerance, syncope, and prerenal azotemia. 
• High hydrostatic pulmonary venous pressure 
causes leakage of fluid from pulmonary venous 
circulation into pulmonary interstitium and 
alveoli; when fluid leakage exceeds ability of 
lymphatics to drain affected areas, pulmonary 
edema develops.
• All systems can be affected by poor 
perfusion. • Respiratory—increased rate and 
effort because of elevated pulmonary venous 
pressures/edema. • Cardiovascular.
GENETICS
Some congenital heart defects, cardiomyo­
pathies, and valvular heart disease have 
genetic basis in some breeds.
Common
Seen everywhere; prevalence of causes varies 
with location.
Species
Varies with cause.
SIGNS
Signs vary with underlying cause and species.
• Weakness, lethargy, exercise intolerance. 
• Coughing (dogs with large left atria, 
concurrent tracheobronchial disease, or such 
severe edema that large airways affected) and 
dyspnea (increased respiratory rate and effort); 
respiratory signs often worsen at night and may 
require assuming standing, sternal, or “elbows 
abducted” position (orthopnea). • Cats rarely 
cough from heart failure; coughing should 
prompt search for primary airway disease.
• Tachypnea and dyspnea. • Coughing, often 
soft in conjunction with tachypnea (dogs). 
• Pulmonary crackles and wheezes. • Pale/
gray/cyanotic mucous membranes. 
• Prolonged capillary refill time. • Possible 
murmur or gallop. • Weak femoral pulses.CAUSES
Pump (Muscle) Failure of Left Ventricle
• Dilated cardiomyopathy (DCM)/diet ­induced 
DCM. • T rypanosomiasis (rare). • Doxorubicin 
cardiotoxicity (dogs). • Hypothyroidism (rare). 
• Hyperthyroidism (rarely causes pump failure; 
more commonly causes high output failure). 
• Tachycardia ­induced cardiomyopathy (caused 
by persistent pathologic supraventricular or 
ventricular tachyarrhythmia).
Pressure Overload of Left Heart
• Systemic hypertension (uncommon cause 
of heart failure in animals). • Subaortic 
stenosis. • Aortic coarctation (rare; Airedale 
predisposed). • Left ventricular tumors (rare).
Volume Overload of Left Heart
• Degenerative mitral valve disease (dogs). 
• Mitral valve dysplasia (cats and dogs). 
• Patent ductus arteriosus (dogs). • Ventricular 
septal defect, especially if complicated by aortic 
valve insufficiency. • Aortic valve insufficiency 
secondary to endocarditis (dogs). • Chronic, 
severe anemia. • Inadvertent high ­volume fluid 
administration. • Steroid administration (cats, 
often with previously asymptomatic underlying 
hypertrophic cardiomyopathy [HCM]).
Impediment to Filling of Left Ventricle
• Restrictive cardiomyopathy (rare in dogs, 
more common in cats). • Pulmonary vein 
stenosis (rare). • HCM. • Left atrial masses 
(e.g., tumor or thrombus). • Mitral stenosis 
(rare). • Cor triatriatum sinister (cats, rare).
Rhythm Disturbances
• Bradyarrhythmia (high ­grade atrioventricular 
block). • Tachyarrhythmia (e.g., atrial 
fibrillation, sustained supraventricular tachy  ­ 
cardia, ventricular tachycardia).
Conditions causing chronic high cardiac 
output (e.g., hyperthyroidism and anemia).
  DIAGNOSIS
Must differentiate from other causes of 
coughing, dyspnea, and weakness.
• CBC usually normal; maybe stress leuko ­ 
gram. • Mild to moderate liver enzyme 
elevation; bilirubin generally normal. 
• Thyroid disorders may be detected. 
• Serum NT ­proBNP and cardiac troponin I 
concentrations higher in animals with 
left­sided congestive heart failure (L ­CHF) 
than in normal animals.
IMAGING
• Left heart and pulmonary veins enlarged. 
• Pulmonary edema, often hilar, especially involving right caudal lung lobe in acute 
edema of dog, but may be patchy, especially 
in cats; acute pulmonary edema may begin in 
right caudal lung lobe.
• Findings vary markedly with cause, but left 
atrial enlargement relatively consistent finding 
in cardiogenic pulmonary edema. • Diagnostic 
test of choice for documenting congenital 
defects, cardiac masses, and pericardial effusion.
ECG
• Atrial or ventricular arrhythmias. 
• Evidence of left cardiomegaly (e.g., wide P 
waves, tall and wide QRS complexes, and left 
axis orientation). • May be normal.
Cardiac findings vary with disease.
  TREATMENT
• Usually treat as outpatient unless dyspneic 
or severely hypotensive. • Identify and correct 
underlying cause whenever possible. 
• Minimize handling of critically dyspneic 
animals—stress can kill!
Oxygen supplementation and postural 
support in dyspneic patients.
ACTIVITY
Restrict activity when dyspneic or tachypneic.
DIET
Initiate moderately sodium ­restricted diet with 
adequate protein and calories. Severe sodium 
restriction indicated with advanced disease.
With few exceptions (e.g., animals with thyroid 
disorders, anemia, arrhythmias, nutritionally 
responsive heart disease, congenital heart 
disease), L ­CHF is not curable.
• Surgical intervention, coil embolization, 
Amplatz occluder placement, or balloon 
valvuloplasty may benefit selected patients 
with some forms of congenital and acquired 
valvular heart disease; response to these 
interventions varies. • Pericardiocentesis in 
animals with pericardial effusion.
Diuretics
• Furosemide (1–2 mg/kg q8–24h) or other 
loop diuretic is initial diuretic of choice; diuretics 
indicated to reduce preload and remove 
pulmonary edema; critically dyspneic animals 
often require high doses (2–4 mg/kg) IV to

316  Blackwell’s Five-Minute Veterinary Consult  
Cstabilize; dose can be repeated in 1h if animal still 
severely dyspneic; IV bolus of 0.66 mg/kg 
followed by CRI of 0.66–1 mg/kg/h for 1–4h 
causes greater diuresis than equal dose divided 
into two IV boluses given 4h apart; once edema 
resolves, taper to lowest effective dose. 
• Spironolactone (0.5–2 mg/kg PO q12–24h) 
increases survival in humans with CHF and is in 
clinical trials in dogs; use in combination with 
furosemide. • Thiazide diuretics can be added to 
furosemide and spironolactone in refractory 
heart failure cases. • Torsemide (0.2–0.8 mg/kg 
q24h) may be useful as substitute for furosemide 
in animals requiring daily furosemide dosing in 
excess of 12 mg/kg, and it may be more effective 
than furosemide at delaying death due to cardiac 
disease in dogs with CHF secondary to degen  ­ 
erative valve disease.
Angiotensin-Converting Enzyme ACE) 
• ACE inhibitors such as enalapril (0.5 mg/kg 
q12–24h) or benazepril (0.25–0.5 mg/kg 
q12–24h) indicated in most animals with 
L­CHF . • ACE inhibitors improve survival and 
quality of life in dogs with L ­CHF secondary to 
degenerative valve disease and DCM.
Positive Inotropes
• Pimobendan (0.25–0.3 mg/kg PO q12h) is a 
calcium channel sensitizer that dilates arteries and 
increases myocardial contractility; first ­line agent 
in treating DCM or CHF due to degenerative 
valve disease efficacy in cats with CHF is not 
known, but possibly beneficial. • Dobutamine 
(dogs: 2.5–10  μg/kg/min; cats: 0.5–5  μg/kg/
min) is a potent positive inotropic agent that 
may provide valuable short ­term support of a 
heart failure patient with poor cardiac 
contractility. • Positive inotropes in general are 
potentially arrhythmogenic—monitor carefully.
Venodilators
• Nitroglycerin ointment (one ­fourth 
inch/5 kg q6–8h) causes venodilation, lowering 
left atrial filling pressures. • Used for acute 
stabilization of patients with severe pulmonary 
edema and dyspnea, but uncertain benefit.
Antiarrhythmic Agents
T reat arrhythmias if clinically indicated.
Avoid vasodilators in patients with pericardial 
effusion or fixed outflow obstruction.
• ACE inhibitors and arterial dilators must be 
used with caution in patients with possible 
outflow obstruction. • Pulmonary hypertension, 
hypothyroidism, and hypoxia increase risk for 
digoxin toxicity; hyperthyroidism diminishes 
effects of digoxin. • ACE inhibitors and 
digoxin—use cautiously in patients with renal 
disease. • Dobutamine—use cautiously in cats. 
• Spironolactone—may cause facial pruritis 
in cats.
• Combination of high ­dose diuretics and 
ACE inhibitors may cause azotemia, especially in animals with severe sodium 
restriction. • Combination diuretic therapy 
adds to risk of dehydration and electrolyte 
disturbances. • Combination vasodilator 
therapy predisposes animal to hypotension.
Arterial Dilators
• Hydralazine (0.5–2 mg/kg PO q12h; 
0.5 mg/kg PO to start when added to ACE 
inhibitor) or amlodipine (0.05–0.2 mg/kg 
PO q24h) can be substituted for ACE 
inhibitor in patients that do not tolerate the 
drug or have advanced renal failure; monitor 
for hypotension and tachycardia; can be 
cautiously added to ACE inhibitor in animals 
with refractory L ­CHF . • Nitroprusside 
(1–10  μg/kg/min) is potent arterial dilator 
usually reserved for short ­term support of 
patients with life ­threatening edema.
Digoxin
• Digoxin (dogs: 0.22 mg/m2 q12h; cats: 
0.01 mg/kg q48h) is used in animals with 
atrial fibrillation and myocardial failure (e.g., 
DCM); commonly used in combination with 
diltiazem to control rate of atrial fibrillation. 
• Digoxin is also indicated to treat dogs with 
refractory heart failure from either myocardial 
failure or volume loads; however, its use as a 
primary agent in myocardial failure has been 
replaced by pimobendan.
Calcium Channel Blockers
Diltiazem (0.5–1.5 mg/kg PO q8h) is frequently 
used in L ­CHF patients for rate control in 
animals with supraventricular arrhythmias.
• Atenolol and metoprolol are sometimes used 
for rate control in animals with supraventricular 
tachycardia, hypertrophic cardiomyopathy, and 
hyperthyroidism. • Used alone or with a class 1 
antiarrhythmic drug for control of ventricular 
arrhythmias; these drugs depress contractility 
(negative inotropes), so use cautiously in patients 
with myocardial failure or active signs of CHF . 
• On basis of human studies, may enhance 
survival in animals with idiopathic DCM; 
treatment is best initiated under guidance of a 
cardiologist, starting with very low dosage and 
gradually increasing; carvedilol is sometimes used 
for this purpose, starting at 0.1 mg/kg q24h and 
titrating to 0.5 mg/kg q12h.
Nutritional Supplements
• Potassium and magnesium supplementation 
if deficiency is documented; use potassium 
supplements cautiously in animals receiving 
ACE inhibitor or spironolactone. • Taurine 
supplementation in cats with DCM and dogs 
with DCM and taurine deficiency (e.g., 
American cocker spaniels) • L­carnitine 
supplementation may help some dogs with 
DCM. • Coenzyme Q10 is of potential value 
based on results in humans with DCM. 
• Ensure animal receiving a nutritionally 
balanced diet (see Cardiomyopathy, 
Nutritional).  FOLLOW-UP
• Monitor resting respiratory rate and effort, 
appetite, renal status, electrolytes, hydration, heart 
rate, bodyweight. • If azotemia develops, reduce 
diuretic dose; if azotemia persists and animal is 
also on ACE inhibitor, reduce or discontinue 
ACE inhibitor; use digoxin with caution if 
azotemic. • Monitor ECG if arrhythmias 
suspected. • Check digoxin concentration 
(0.5–1.5 ng/mL, 8–10 hours post dose).
• Minimize stress, exercise, and sodium 
intake in patients with heart disease. 
• Pimobendan delays onset of CHF in 
Doberman pinschers, and in dogs with 
hemodynamically significant myxomatous 
mitral valve regurgitation; prescribing an 
ACE inhibitor with pimobendan early in 
course of heart disease in patients with DCM 
may slow progression of heart disease and 
delay onset of CHF; role of ACE inhibitors in 
asymptomatic animals with mitral valve 
disease remains controversial.
• Syncope. • Aortic thromboembolism (cats). 
• Arrhythmias. • Electrolyte imbalances. 
• Digoxin toxicity. • Azotemia and renal 
failure.
Prognosis varies with underlying cause; cats 
and dogs that survive initial episode of 
pulmonary edema and can be reliably 
medicated often survive months to more than 
a year with good quality of life. Animals with 
reversible causes of L ­CHF may recover to 
normal lives.
• Congenital causes seen in young animals. 
• Degenerative heart conditions and 
neoplasia generally seen in old animals.
SEE ALSO
Pulmonary Edema, Noncardiogenic.
• HCM = hypertrophic cardiomyopathy. 
• L­CHF = left ­sided congestive heart failure.
Authors  Francis W.K. Smith, Jr. and Bruce 
W. Keene
available onlineCongestive Heart Failure, Left-Sided  (continued)

Canine and Feline, Seventh Edition  317
C
 BASICS
Failure of the right side of the heart to 
advance blood at a sufficient rate to meet the 
metabolic needs of the patient or to prevent 
blood from pooling within the systemic 
venous circulation.
• High hydrostatic pressure leads to leakage of 
fluid from venous circulation into the pleural 
and peritoneal space and potentially into the 
pericardium and interstitium of peripheral 
tissue. • When fluid leakage exceeds ability of 
lymphatics to drain the affected areas, pleural 
effusion, ascites, pericardial effusion, and 
peripheral edema develop.
All systems can be affected by either poor 
delivery of blood or the effects of passive 
congestion from backup of venous blood.
GENETICS
• Some congenital cardiac defects have a genetic 
basis in certain breeds. • Arrhythmogenic right 
ventricular cardiomyopathy (ARVC) appears to 
have a genetic basis in boxers and possibly some 
cats.
Common
Syndrome seen everywhere; prevalence of 
various causes varies with location.
Species
Vary with cause.
SIGNS
• Signs vary with underlying cause and 
between species. • Pleural effusion without 
ascites and hepatomegaly is rare in dogs 
with right-sided congestive heart failure 
(R-CHF). • Ascites without pleural 
effusion is rare in cats with R-CHF .  
• Small-volume pericardial effusion 
without tamponade is relatively common 
in cats with R-CHF . • Interstitial periph -
eral edema is a rare manifestation of 
R-CHF in both species.
• Weakness. • Lethargy. • Exercise intolerance. 
• Abdominal distension. • Dyspnea, tachypnea.Physical Examination Findings
• Jugular venous distention. • Hepatojugular 
reflux. • Jugular pulse in some animals.  
• Hepatomegaly. • Ascites common in dogs 
and rare in cats with R-CHF . • Possible 
r egurgitant murmur in tricuspid valve 
region or ejection murmur at left heart base 
(pulmonic stenosis). • Muffled heart sounds 
if animal has pleural or pericardial effusion.  
• Weak femoral pulses. • Rapid, shallow 
respiration if animal has pleural effusion or 
severe ascites.• Peripheral edema (infrequent).
CAUSES
Pump (Myocardial) Failure of Right 
Ventricle
• Idiopathic dilated cardiomyopathy (DCM). 
• ARVC. • Hypertrophic cardiomyopathy 
(cats). • Restrictive cardiomyopathy (cats).  
• T rypanosomiasis. • Doxorubicin 
c ardiotoxicity. • Chronic hyperthyroidism.
Volume Overload of Right Ventricle
• Chronic atrioventricular (AV) valve (mitral 
± tricuspid) insufficiency due to myxomatous 
valvular degeneration. • T ricuspid valve 
dysplasia. • Large atrial septal defect.
Pressure Overload of Right Ventricle
• Heartworm disease. • Chronic obstructive 
pulmonary disease with pulmonary hypertension. 
• Pulmonary thromboembolism. • Pulmonic 
stenosis. • Tetralogy of Fallot. • Right ventricular 
tumors. • Heart base tumors (occasionally, 
compression of the pulmonary artery). • Primary 
pulmonary hypertension.
Impediment to Right Ventricular Filling
• Pericardial effusion (tamponade). • Constrictive/
restrictive pericarditis. • Right atrial or caval masses. 
• T ricuspid stenosis. • Cor triatriatum dexter.
• Bradycardia, generally complete AV block. 
• Tachyarrhythmias, generally sustained 
supraventricular tachycardia.
• No heartworm prophylaxis. • Offspring of 
animal with right-sided congenital cardiac 
defect. • Conditions that augment demand 
for cardiac output (e.g., hyperthyroidism, 
anemia, pregnancy).
 DIAGNOSIS
• Must differentiate from other causes of 
pleural effusion and ascites; generally 
requires complete diagnostic workup 
including CBC, biochemistry profile, 
heartworm test, thoraco- or abdominocen -
tesis with fluid analysis and cytology, and 
sometimes thoracic and abdominal 
ultrasound. • Animals with ascites or pleural effusion due to heart failure should have 
jugular venous distension.
• CBC usually normal; animals with 
heartworm disease may have eosinophilia.  
• Mild to moderately high alanine aminotrans   
ferase, aspartate aminotransferase, and 
alkaline phosphatase due to passive liver 
congestion; bilirubin generally normal.  
• Heartworm test may be positive. • NT-proBNP 
concentrations higher in animals with cardiac 
causes of fluid accumulation.
IMAGING
• Right cardiomegaly in some animals.  
• Dilated caudal vena cava (diameter greater 
than the length of the vertebra directly above 
the heart). • Pleural effusion (especially cats). 
• Hepatosplenomegaly and possible ascites 
(especially dogs).
• Findings vary with underlying cause; 
especially useful for documenting congenital 
defect, cardiac mass, and pericardial effusion. 
• Abdominal ultrasound reveals hepatomeg -
aly with hepatic vein dilation, flow reversal in 
the hepatic veins (Doppler), and possibly 
ascites.
ECG Findings
• Small (<1 mV) QRS complexes in all frontal 
axis leads if pericardial or pleural effusion.  
• Electrical alternans or elevated ST segment 
with pericardial effusion. • Evidence of right 
cardiomegaly (e.g., tall [ >0.4 mV] P waves in 
lead II, deep S waves in leads I, II, aVF , and 
right axis deviation). • Atrial or ventricular 
arrhythmias. • ECG may be normal.
Abdominocentesis
Analysis of ascitic fluid in patients with 
R-CHF generally reveals modified transudate 
with total protein >2.5 mg/dL.
Thoracentesis
• Cats with pleural effusion associated with 
R-CHF may have transudate, modified 
transudate, or chylous effusion. • Dogs with 
pleural effusion and R-CHF may have 
transudate or modified transudate.
Central Venous Pressure
Central venous pressure is high ( >9 cmH2O) 
or rises dramatically to that level and remains 
elevated for more than 1h following a fluid 
bolus (e.g., 5–10 mL/kg IV).
• Cardiac findings vary with disease.  
• Hepatomegaly in animals with centrolobu-
lar necrosis (chronic condition).Congestive Heart Failure, Right-Sided

318  Blackwell’s Five-Minute Veterinary Consult  
C
 TREATMENT
Most animals treated as outpatients unless 
dyspneic or collapsed (e.g., significant pleural 
or pericardial effusion).
Thoracentesis and abdominocentesis may be 
required periodically for patients no longer 
responsive to medical management or those 
with severe dyspnea due to pleural effusion or 
ascites.
ACTIVITY
Restrict activity.
DIET
Restrict sodium moderately; severe sodium 
restriction indicated for animals with 
• With few exceptions (e.g., in heartworm 
disease, arrhythmias, hyperthyroidism, and 
idiopathic pericardial effusion), R-CHF is not 
curable. • Most patients improve with initial 
treatment but often have recurrent failure.
• Surgical intervention or balloon valvuloplasty 
is indicated to treat certain congenital defects 
such as pulmonic stenosis or cor triatriatum 
dexter, and Amplatz occluder placement for 
morphologically appropriate atrial septal 
defects. • Pericardiocentesis or pericardectomy 
for pericardial effusion. • Removal of heart -
worms from the heart via the jugular vein in 
dogs with caval syndrome.
Drugs should be administered only after a 
definitive diagnosis is made.
Diuretics
• Furosemide (1–2 mg/kg q8–24h) or another 
loop diuretic is the initial diuretic of choice; 
diuretics are indicated to remove excess fluid 
accumulation. • Torsemide (0.2–0.8 mg/kg 
q24h) may be a useful substitute for furosem -
ide in animals requiring a daily furosemide 
dose in excess of 12 mg/kg. • Spironolactone 
(2 mg/kg PO q12–24h) increases survival in 
humans with heart failure; use in combination 
with furosemide.Vasodilators
• Angiotensin-converting enzyme (ACE) 
inhibitors such as enalapril (0.5 mg/kg 
q24h) are helpful when CHF is secondary to 
DCM or chronic AV valve insufficiency.  
• Sildenafil (0.5–1 mg/kg PO q12h up to 
2–3 mg/kg q8h) may be beneficial for 
• Calcium sensitizer that acts as an inodilator, 
causing arterial vasodilation and increasing 
myocardial contractility. • Especially useful in 
myocardial failure. • Dose—0.25–0.3 mg/kg 
PO q12h.
Digoxin
0.01 mg/kg q48 h) is used in animals with 
myocardial failure (e.g., DCM) and atrial 
fibrillation. • Digoxin indicated in animals 
with refractory CHF that have supraventricu-
lar arrhythmias.
• Avoid diuretics in patients with pericardial 
effusion/tamponade. • Avoid vasodilators in 
patients with pericardial effusion or fixed 
outflow obstructions.
outflow obstructions. • Pulmonary hyperten-
sion, hypothyroidism, and hypoxia increase 
risk for digoxin toxicity; hyperthyroidism 
diminishes effects of digoxin. • ACE 
inhibitors and digoxin—use cautiously with 
renal disease. • Dobutamine—use cautiously 
in cats. • Spironolactone—may cause facial 
pruritis in cats.
• Combination of high-dose diuretics and 
ACE inhibitors may alter renal perfusion and 
cause azotemia. • Combination diuretic 
therapy promotes risk of dehydration and 
electrolyte disturbances.
• Patients unresponsive to furosemide, 
spironolactone, vasodilator, pimobendan, and 
digoxin (if indicated) may benefit from triple 
diuretic therapy by adding a thiazide diuretic, 
or substitution of torsemide for furosemide, 
generally at 0.1–0.2 mg of torsemide for each 
1 mg of furosemide previously administered. 
if deficiency documented; use potassium 
ACE inhibitors or spironolactone. • T reat arrhythmias if clinically indicated. • Taurine 
with DCM and taurine deficiency. • Carnitine 
DCM (e.g., cocker spaniels and boxers).
 FOLLOW-UP
• Monitor renal status, electrolytes, hydration, 
respiratory rate and effort, bodyweight, and 
abdominal girth (dogs). • If azotemia develops, 
reduce diuretic dosage; if azotemia persists and 
the animal is also on an ACE inhibitor, reduce or 
discontinue this drug; if azotemia develops, 
reduce digoxin dosage to avoid toxicity.  
• Monitor ECG periodically to detect arrhyth -
mias. • Monitor digoxin concentrations—  
normal value 0.5–1.5 ng/mL for serum sample 
obtained 8–10h after dose is administered.
• Pulmonary thromboembolism. • Arrhythmias. 
• Electrolyte imbalances. • Digoxin toxicity.  
• Azotemia and renal failure.
Prognosis varies with underlying cause.
SEE ALSO
• Ascites.
• Chylothorax.
• Pleural Effusion.
• R-CHF = right-sided congestive heart failure.
W. Keene
available onlineCongestive Heart Failure, Right-Sided  (continued)

Canine and Feline, Seventh Edition  319
C
 BASICS
Inflammation of the conjunctiva, the 
vascularized mucous membrane that covers 
the anterior sclera (bulbar conjunctiva), lines 
the eyelids (palpebral conjunctiva), and lines 
the third eyelid.
May be primary or secondary to adnexal or 
ocular disease.
GENETICS
N/A
Common
N/A
Species
Cat
Infectious—purebred cats may be 
predisposed.
Infectious—commonly affects young animals.
N/A
SIGNS
• Blepharospasm. • Conjunctival hyperemia. 
• Ocular discharge—serous, mucoid, or 
mucopurulent. • Chemosis. • Conjunctival 
follicles. • Upper respiratory infection—pos-
sible with infectious etiologies.
CAUSES
Viral
• Feline herpesvirus (FHV)—most common 
infectious cause; only one that leads to 
corneal changes (e.g., dendritic or geographic 
ulcers). • Calicivirus—may cause conjuncti-
val ulcerations.
Bacterial
• Chlamydophila felis —chemosis is common 
clinical sign. • Mycoplasma  spp.—may be 
overgrowth of normal flora. • Conjunctivitis 
neonatorum—accumulation of exudates 
under closed eyelids prior to natural opening; 
bacterial or viral component.
Immune-Mediated
• Eosinophilic. • Lipogranulomatous. 
• Allergic. • Related to systemic immune-
mediated disease.
Trauma or Environmental Causes
• Conjunctival foreign body. • Irritation from dust, 
smoke, chemicals, or ophthalmic medications.Secondary to Adnexal Disease
• May develop keratoconjunctivitis sicca 
(KCS) as a result of scarring. • Eyelid diseases 
(e.g., entropion, trichiasis, distichia, or eyelid 
agenesis)—cause frictional irritation or 
exposure. • Dacryocystitis or nasolacrimal 
system outflow obstruction.
Referred Inflammation from Other 
Ocular or Periocular Diseases
• Ulcerative keratitis. • Corneal sequestrum. 
• Anterior uveitis. • Glaucoma. • Orbital 
disease. • Pyoderma.
Stress or immune system compromise (FHV).
 DIAGNOSIS
• Must distinguish primary conjunctivitis from 
secondary conjunctival hyperemia. • Thorough 
ophthalmic exam rules out other diseases (e.g., 
ulcers, uveitis, glaucoma, orbital disease); assess 
pupil size and symmetry, look for aqueous flare, 
perform intraocular pressure testing and 
fluorescein staining. • Deeper, darker, more 
linear and immobile blood vessel injection 
indicates episcleral vasculature congested due to 
intraocular disease. • Conjunctival mass biopsy 
will identify neoplasia (lymphoma and 
squamous cell carcinoma most common).
Normal, except with systemic disease.
Infectious—serologic testing for feline 
leukemia virus (FeLV) and feline immuno  - 
IMAGING
N/A
• Thorough adnexal examination—rule out 
eyelid abnormalities and foreign bodies under 
eyelids or third eyelid. • Complete ophthal-
mic examination—rule out other ocular 
disease (e.g., uveitis, glaucoma). • Fluorescein 
stain—assess for corneal ulceration or dendritic 
lesions (FHV) and observe nares for stain 
passage to indicate nasolacrimal system 
patency. • Nasolacrimal flush—considered to 
rule out dacryocystitis or nasolacrimal system 
obstruction. • Schirmer tear test—measures 
aqueous tears to diagnose or rule out KCS; 
performed before anything is placed in the 
eye. • Conjunctival cytology—rarely reveals 
cause; eosinophils with eosinophilic conjunc-
tivitis; degenerate neutrophils and intracyto-
plasmic bacteria indicate bacterial infection; 
intracytoplasmic inclusion bodies indicate 
chlamydial or mycoplasmal infection; rarely 
see intranuclear FHV inclusions. 
• Conjunctival biopsy—“snip biopsy” may be useful with mass lesions and immune-medi-
ated disease or chronic disease. • PCR testing 
for chlamydia or FHV. • Virus isolation or 
immunofluorescence antibody (IFA) testing 
for FHV; false-positive result if fluorescein 
staining is done before IFA testing. 
• Serologic test for FHV antibodies—not 
useful (widespread exposure, vaccination).
• Biopsy—signs of inflammation, possible 
infectious agents. • Histopathology of mass 
lesions may reveal neoplasia (e.g., squamous 
cell carcinoma and lymphoma).
 TREATMENT
• Primary—often outpatient. • Secondary to 
other diseases (ulcerative keratitis, uveitis, 
glaucoma)—may need hospitalization to 
address severe underlying ophthalmic issue.
• Irritant-induced conjunctivitis—flush ocular 
surfaces and remove foreign body if observed. 
• Topical hyaluronate-based artificial tear, q8h 
to benefit tear film. • Frequent cleaning of 
eyelid margins and periocular skin to remove 
ocular discharge.
ACTIVITY
• Generally, no restrictions. • Suspected contact 
irritant or acute allergic disease—prevent contact 
with the offending agent. • Suspected FHV—
minimize stress. • Do not expose patients with 
infectious disease to susceptible animals.
DIET
• No change for most patients. • Suspected 
underlying skin disease and/or food allergy—
food elimination diet.
• When solutions and ointments are prescribed, 
instruct the client to use solution(s) before 
ointment(s) and wait at least 5 minutes between 
treatments. • If copious discharge is noted, 
instruct client to clean eyes before giving 
medication. • Instruct client to call for instruc -
tions if condition fails to improve or worsens.
• Lipogranulomatous conjunctivitis—surgical 
incision and curettage of glandular material 
and inflammatory infiltrates. • Entropion, 
distichia, or other eyelid disease—perform 
temporary or permanent surgery depending on 
the findings, signalment, and history. 
• Nasolacrimal duct obstruction—difficult; 
treatment often not recommended (see 
Epiphora). • Conjunctival neoplasia—depend -
ing on tumor type and extent of involvement, 
may involve local excision and adjunctive 
therapy ( β-irradiation, cryotherapy), enuclea -
tion, or exenteration. • Symblepharon Conjunctivitis—Cats

320  Blackwell’s Five-Minute Veterinary Consult  
C(adhesions between the conjunctiva and 
cornea)—adhesions may require surgical 
resection (poor prognosis). • Corneal 
sequestration—keratectomy often recom -
mended (see Corneal Sequestrum—Cats).
Herpetic
• Condition usually mild and self-limiting. 
• Antiviral treatment—indicated for severe 
intractable conjunctivitis, herpetic keratitis, 
and before keratectomy for corneal sequestra 
suspected to be related to FHV; for all 
antivirals treat 2 weeks past resolution of 
clinical signs. • 0.5% cidofovir solution 
(available from compounding pharmacies)—
topical, q12h. • 0.1% idoxuridine solution or 
0.5% ointment (compounding pharma-
cies)—topical, q4h. • Vidarabine 3% 
ointment—topical, q4h. • T rifluridine 1% 
solution—topical, q4h; potentially irritating. 
• Oral famciclovir is effective and safe; 
recommended dosage 90 mg/kg PO q12h. 
• Lysine 500 mg PO q12h for adult cat 
(250 mg PO q12h for kitten). • FortiFlora® 
probiotic PO q24h may decrease incidence of 
conjunctivitis associated with FHV.
Chlamydial or Mycoplasmal
• Tetracycline, erythromycin, or chloram -
phenicol ophthalmic ointment—topically 
q6–8h; continue for several days past 
resolution of all clinical signs; recurrence or 
reinfection common. • Topical ciprofloxacin 
ophthalmic solution q6–8h as alternative to 
ophthalmic ointment. • Doxycycline 10 mg/
kg PO q24h for 3–4 weeks may be superior to 
or used along with topical treatment. • Based 
on bacterial culture and sensitivity results.
Neonatal
Carefully open the eyelid margins (medial to 
temporal), establish drainage, and treat with 
topical antibiotic ointment q6–8h and an 
antiviral for suspected FHV.
Eosinophilic
• Topical corticosteroid—0.1% dexamethasone 
sodium phosphate q6–8h generally effective; 
taper gradually to lowest effective dose or 
transition to cyclosporine. • Cyclosporine 0.2% ointment 1–2% compounded solution, 
or tacrolimus 0.03% compounded solution—
topical therapy q8–24h. • Topical 0.5% 
megestrol acetate solution (available from 
compounding pharmacies)—q8–12h; safe with 
concurrent corneal ulceration and/or concur -
rent FHV ocular disease. • Oral megestrol 
acetate—may help resistant condition, but 
rarely used given possible systemic side effects.
• Topical corticosteroids—avoid with known 
or suspected infectious conjunctivitis; may 
result in FHV recrudescence and predispose 
to corneal sequestrum formation; never use if 
corneal ulceration is noted. • Valacyclovir 
should never be used in cats.
• Topical medications may be irritating. 
• Monitor all patients treated with topical 
corticosteroids for signs of corneal ulceration; 
discontinue agent immediately if corneal 
ulceration occurs.
N/A
Other corticosteroids—1% prednisolone 
acetate.
 FOLLOW-UP
Recheck shortly after beginning treatment (at 
5 days), then in 2 weeks or as needed.
• T reat any underlying disease that may be 
exacerbating the conjunctivitis. • Minimize 
stress for patients with herpetic disease. • Isolate 
patients with infectious conjunctivitis to prevent 
spread. • Prevent reexposure to infectious 
sources. • Vaccination recommended; infection 
is still possible if the cat was exposed to an 
infectious agent before being vaccinated (e.g., 
FHV infection from an infected queen).
• Corneal sequestration (see Corneal 
Sequestrum—Cats)—usually requires surgical 
keratectomy. • Symblepharon—may require 
surgery. • KCS—most likely from chronic 
FHV.EXPECTED COURSE AND PROGNOSIS
• FHV—most patients become chronic 
carriers; may see repeated exacerbations, but 
episodes less common as patient matures; more 
severe clinical signs at times of stress or 
immunocompromise. • Bacterial conjunctivi -
tis—usually resolves with appropriate admin  - 
istration of antibiotic. • Immune-mediated 
diseases (e.g., eosinophilic)—control not cure; 
may require chronic treatment at lowest level 
possible. • If underlying disease is found (e.g., 
KCS, entropion), resolution may depend on 
appropriate treatment of the disease.
FeLV and FIV—may predispose patient to 
chronic carrier state of FHV conjunctivitis.
FHV—tends to be more severe in kittens and 
in old cats with waning immunity.
Chlamydophila felis —low.
Use topical and systemic medications with 
caution, if at all, in pregnant animals.
SEE ALSO
• Corneal Sequestrum—Cats.
• Keratoconju  nctivitis Sicca.
• Red Eye.
• IFA = immunofluorescent antibody.
Maggs DJ, Miller PE, Ofri R. Slatter’s 
Elsevier, 2018, pp. 158–177.
Author  Rachel A. Allbaugh
available onlineConjunctivitis—Cats  (continued)

Canine and Feline, Seventh Edition  321
C
 BASICS
• Primary—allergic, infectious, e  nvironmental. 
• Secondary to other ocular disease—kerato-
conjunctivitis sicca (KCS), entropion, 
distichiasis.
GENETICS
N/A
Common
N/A
Species
Dog
Breeds predisposed to allergic or immune-
mediated skin diseases (e.g., atopy) tend to have 
more problems with allergic conjunctivitis or 
KCS.
N/A
None
SIGNS
• Blepharospasm. • Conjunctival hyper -
emia. • Ocular discharge—serous, mucoid, 
or mucopurulent. • Chemosis. • Follicle 
formation on posterior third eyelid surface. 
• Enophthalmos and third eyelid elevation.
CAUSES
• Bacterial—rare as primary condition, 
usually secondary to KCS; conjunctivitis 
neonatorum involves accumulation of 
exudates under closed eyelids prior to natural 
opening. • Viral—canine herpes virus-1, 
canine distemper virus, or canine adenovi-
rus-2. • Parasitic— Leishmania , Onchocerca , 
or Thelazia . • Conjunctival manifestation of 
systemic infectious disease
• Allergic—especially in atopic patients. 
• Follicular conjunctivitis—common in 
dogs <18 months, secondary to chronic 
antigenic stimulation. • Lymphocytic/
plasmacytic conjunctivitis—especially in 
German shepherd dogs with or without chronic superficial keratitis (pannus). 
• Systemic immune-mediated disease (e.g., 
pemphigus).
• Conjunctival foreign body. • Irritation (dust, 
smoke, ophthalmic medications). • Toxin or 
chemical contact.
Other
Ligneous conjunctivitis—rare, young female 
Dobermans may be predisposed.
Secondary to Adnexal Disease
• Aqueous tear film deficiency (KCS) or 
qualitative tear deficiency. • Eyelid diseases—
entropion, ectropion, medial canthal pocket 
syndrome, eyelid mass. • Hair or eyelash 
disorders—trichiasis, distichiasis, ectopic cilia. 
• Exposure—facial nerve paralysis, lagoph-
thalmos. • Dacryocystitis or nasolacrimal 
system outflow obstruction (e.g., obstructed 
duct or imperforate punctum).
• Ulcerative keratitis. • Nodular episcleritis. 
Atopy, KCS.
 DIAGNOSIS
• Distinguish primary conjunctivitis from 
systematic ophthalmic exam identifies other 
potential diseases (e.g., KCS, ulcers, uveitis, 
glaucoma, orbital disease); assess pupil size and 
symmetry, look for aqueous flare, attempt globe 
retropulsion, perform Schirmer tear test, 
intraocular pressure measurement, and 
indicates congested episcleral vasculature due to 
episcleritis or intraocular disease. • Mass biopsy 
will differentiate conjunctival neoplasia (rare: 
squamous cell carcinoma, melanoma, 
hemangioma/sarcoma, lymphoma, papilloma, 
mast cell tumor) or episcleritis.
Normal unless systemic disease.
N/A
IMAGING
N/A
• Adnexal examination—rule out facial nerve 
paralysis, lagophthalmos, eyelid abnormalities, 
hair or eyelash disorders, and foreign bodies in 
cul-de-sacs or under third eyelid. • Schirmer tear 
test—rule out KCS; perform before anything else is placed in eye. • Fluorescein stain—no 
corneal retention rules out ulcerative keratitis; 
stain flow to nares rules out n  asolacrimal disease. 
• Tear film breakup time—assesses tear film 
stability to rule out qualitative tear deficiency. 
• Intraocular pressures—rule out glaucoma. 
• Globe retropulsion—rule out orbital disease. 
• Examine for signs of anterior uveitis (e.g., 
hypotony, aqueous flare, miosis) or other 
intraocular disease (e.g., cataracts, lens luxation). 
• Consider nasolacrimal duct flush if fluorescein 
stain did not pass to nares. • Conjunctival 
cytology—lymphocytes and plasma cells 
diagnostic for lymphocytic/plasmacytic 
conjunctivitis; eosinophils in allergic 
c onjunctivitis; degenerate neutrophils and 
intracellular bacteria with bacterial infection; 
rarely distemper virus intracytoplasmic 
inclusions. • Conjunctival biopsy—may be 
useful with mass lesions and nodular episcleritis 
or chronic undiagnosed disease. • PCR or viral 
isolation testing for canine herpesvirus-1. 
• Intradermal skin testing—if suspect allergic 
conjunctivitis.
• Biopsy—inflammation, may note infectious 
agents, neoplasia, or nodular episcleritis. 
• Ligneous conjunctivitis—thick, amorphous 
eosinophilic hyaline-like material.
 TREATMENT
• Primary—outpatient. • Secondary to other 
disease (e.g., ulcerative keratitis, uveitis, 
glaucoma, lens luxation)—may require 
hospitalization to address underlying 
ophthalmic issue.
• Allergic or follicular conjunctivitis—apply 
viscous artificial tear gel to both eyes before 
patient is active outdoors (q8–12h), then flush 
ocular surface with eye wash when returning 
indoors to remove “trapped” allergens. 
• Secondary to ectropion or medial canthal 
pocket syndrome—flush ocular surface with 
eye wash daily to remove dust, dirt, or other 
matter that collects ventrally. • Warm pack 
eyelids and periocular skin to soften crusted 
secretions and improve comfort.
ACTIVITY
• No restriction for most. •  Suspected contact 
irritant or allergic disease—prevent contact with 
offending agent. •  Do not expose patients with 
infectious viral disease to susceptible animals.
DIET
• No change for most. • Suspected u  nderlying 
skin disease and/or food allergy—food 
elimination diet trial.Conjunctivitis—Dogs

322  Blackwell’s Five-Minute Veterinary Consult  
the client should use solution(s) before 
ointment(s) and wait 5 minutes between 
clean eyes before giving medication. • Call for 
instructions if condition fails to improve or 
worsens. • An Elizabethan collar should be 
placed on the patient to prevent self-trauma.
• Follicular conjunctivitis—if follicles are 
unresponsive to medication, consider debride -
ment. • Entropion, distichia, ectopic cilia, or 
other eyelid disease—perform temporary or 
permanent surgery depending on findings, 
signalment, and history. • Nasolacrimal duct 
obstruction—if repeated flushing attempts at 
weekly intervals along with medical therapy are 
unsuccessful, consider contrast study and 
surgery (see Epiphora). • Conjunctival 
neoplasia—depending on tumor type and 
extent of involvement, may involve local 
excision and adjunctive therapy ( β-irradiation, 
cryotherapy), enucleation, or exenteration.
Bacterial
• Initial treatment—broad-spectrum topical 
triple antibiotic q6–8h continuing several 
days past resolution of clinical signs; revise 
based on bacterial culture and sensitivity 
results. • Systemic antibiotic (e.g., cephalo-
sporin)—occasionally indicated, especially for 
more generalized disease (e.g., pyoderma).
Neonatal
Carefully open eyelid margins (medial to 
lateral), establish drainage, and treat with 
topical antibiotic ointment q6–8h.
Herpetic
intractable canine herpesvirus-1 c  onjunc -
tivitis or herpetic keratitis. • 0.15% 
ganciclovir gel—topical q4h for 7 days, 
then q8h. • 1% trifluridine s  olution—
topical q4h for 2 days, then q6h. • 0.1% 
idoxuridine solution (compounding 
pharmacies)—t  opical q4h for 2 days, then 
q6h. • 0.5% cidofovir solution 
(c ompounding ph  armacies)—topical q12h; 
generally avoided: reduces duration of 
shedding but may worsen clinical disease 
due to local ocular toxic effects.Immune-Mediated
• Depends on severity. • Allergic and 
follicular conjunctivitis—attempt nursing 
care first with viscous artificial tear gel 
lubricants and ocular flushing q8–12h; if 
nonresponsive consider antihistamine eye 
drops (e.g., ketotifen) q8–12h, or topical 
corticosteroid (e.g., dexamethasone) q8–12h. 
• Lymphocytic/plasmacytic conjunctivi-
tis—0.1% dexamethasone q8h, then taper 
gradually to lowest effective dose; could 
attempt transition to cyclosporine 0.2% 
ointment, cyclosporine 1–2% compounded 
solution q12–24h, or tacrolimus 0.03% 
compounded solution q12–24h. • T reatment 
of any underlying disease (e.g., atopy) often 
improves clinical signs of allergic conjunc  - 
tivitis.
Tear Deficiencies
• Aqueous tear film deficiency (see 
Keratoconjunctivitis Sicca). •  Qualitative tear 
deficiency—cyclosporine 0.2% ointment, 
cyclosporine 1–2% compounded solution 
q12h, or tacrolimus 0.03% compounded 
solution q12–24h, and viscous artificial tear 
lubricants q6–12h.
Topical corticosteroids—avoid if corneal 
ulceration is present, patient is at high risk for 
ulceration (e.g., entropion, lagophthalmos, 
severe KCS), or with known or suspected 
infectious conjunctivitis.
• Topical medications may be irritating. • Topical 
corticosteroids—monitor all patients carefully for 
signs of corneal ulceration; discontinue agent 
immediately if corneal ulceration occurs.
N/A
acetate, betamethasone, hydrocortisone.
 FOLLOW-UP
5 days), then recheck in 2 weeks or as needed.
T reat any underlying disease that may be 
exacerbating the conjunctivitis (e.g., KCS, 
allergic or immune-mediated skin disease).
N/AEXPECTED COURSE AND PROGNOSIS
• Good prognosis when underlying cause 
identified and treated (e.g., KCS, adnexal disease, 
eyelash disorder). • Bacterial—usually resolves 
with appropriate antibiotics; may depend on 
control of underlying disease (e.g., KCS). 
• Allergic or follicular—nursing care or medical 
treatment may be needed during peak allergy 
times. • Lymphocytic/plasmacytic—tend to be 
controlled and not cured; may require chronic 
treatment at lowest level possible.
• Atopy. • Pyoderma.
N/A
N/A
SEE ALSO
• Keratoconjunctivitis Sicca.
• Red Eye.
Hendrix DVH. Diseases and surgery of the 
canine conjunctiva and nictitating 
membrane. In: Gelatt KN, Gilger BC, 
Kern T, eds., Veterinary Ophthalmology, 
pp. 945–975.
available onlineConjunctivitis—Dogs  (continued)

Canine and Feline, Seventh Edition  323
C
 BASICS
• Constipation  is defined as infrequent, 
incomplete, or difficult defecation with 
passage of hard or dry feces. This does not 
imply abnormal motility or loss of function. 
• Obstipation  denotes intractable constipation 
that has failed several consecutive treatments; 
defecation is impossible in the obstipated 
patient.
• Constipation can develop with any disease 
that impairs the passage of feces through the 
colon. Potential causes include congenital 
vertebral malformation, spinal cord disease, 
pelvic canal narrowing (trauma), rectal mass 
lesions causing obstruction, and perianal disease 
causing painful defecation. Often in cats no 
underlying etiology can be identified. • Delayed 
fecal transit allows removal of additional salt and 
water, producing drier feces. Clinical signs are 
attributable to dehydration and potential 
toxemia resulting from fecal retention. 
• Peristaltic contractions may increase during 
constipation, but eventually motility diminishes 
because of smooth muscle degeneration 
secondary to chronic overdistension.
Gastrointestinal.
GENETICS
N/A
Common clinical problem in older cats; less 
common in dogs.
N/A
Species
• Dog and cat. • More common in cat.
N/A
Any age; most common in older cats.
N/A
SIGNS
• Reduced, absent, or painful defecation. 
• Hard, dry feces. • Small amount of 
liquid, mucoid stool, sometimes with 
blood present produced after prolonged 
tenesmus. • Occasional vomiting, 
inappetence, and/or lethargy.
• Colon filled with hard feces. Severe 
impaction may cause abdominal distention. • Other findings depend on underlying 
cause. •  Rectal examination may reveal mass, 
stricture, perineal hernia, anal sac disease, 
foreign body or material, prostatic enlarge-
ment, or narrowed pelvic canal.
CAUSES
Dietary
• Bones. • Hair. • Foreign material. • Excessive 
fiber. • Inadequate water intake.
• Lack of exercise. • Change of environment—
hospitalization, dirty litter box. • Inability to 
ambulate.
Drugs
• Anticholinergics. • Antihistamines. 
• Opioids. • Barium sulfate. • Sucralfate. 
• Antacids. • Kaopectolin. • Iron supple-
ments. • Diuretics.
Painful Defecation (Dyschezia)
• Anorectal disease—anal sacculitis, anal sac 
abscess, perianal fistula, anal stricture, anal 
spasm, rectal foreign body, rectal prolapse, 
proctitis. • T rauma—fractured pelvis, 
fractured limb, dislocated hip, perianal bite 
wound or laceration, perineal abscess.
Mechanical Obstruction
• Extraluminal—healed pelvic fracture with 
narrowed pelvic canal, prostatic hypertrophy, 
prostatitis, prostatic neoplasia, intrapelvic 
neoplasia, sublumbar lymphadenopathy. 
• Intraluminal and intramural—colonic or 
rectal neoplasia or polyp, rectal stricture, 
rectal foreign body, rectal diverticulum, 
perineal hernia, rectal prolapse, congenital 
defect (atresia ani).
Neuromuscular Disease
• Central nervous system—paraplegia, spinal 
cord disease, intervertebral disc disease, 
cerebral disease (lead toxicity, rabies). 
• Peripheral nervous system—  dysautonomia, 
sacral nerve disease, sacral nerve trauma (e.g., 
tail fracture/pull injury). • Colonic smooth 
muscle dysfunction—  idiopathic megacolon 
in cats.
Metabolic and Endocrine Disease
• Impaired colonic smooth muscle 
function—hyperparathyroidism, hypothy -
roidism, hypokalemia (chronic renal 
failure), hypercalcemia. • Debility—  
general muscle weakness, dehydration, 
• Manx cats may be predisposed due to 
vertebral (sacral) abnormalities. • Drug 
therapy—anticholinergics, narcotics, barium 
sulfate. • Metabolic disease causing dehydra-
tion. • Feline dysautonomia. • Intact 
male—perineal hernia, benign or infectious 
prostatic disease. • Castrated male—prostatic 
neoplasia. • Perianal fistula. DIAGNOSIS
• Dyschezia and tenesmus (e.g., caused by 
colitis or proctitis)—unlike constipation, 
associated with increased frequency of 
attempts to defecate and frequent production 
of small amounts of liquid feces containing 
blood and/or mucus; rectal examination 
reveals diarrhea and lack of hard stool. 
• Stranguria (e.g., caused by cystitis/
urethritis)—unlike constipation, can be 
associated with hematuria and abnormal 
findings on urinalysis (pyuria, crystalluria, 
bacteruria).
• Usually unremarkable. • May detect 
hypokalemia, hypercalcemia. • High packed 
cell volume (PCV) and total protein in 
dehydrated patients. • High white blood cell 
(WBC) count in patients with severe 
obstipation secondary to bacterial or 
endotoxin translocation, abscess, perianal 
fistula, prostatic disease. • Pyuria and 
hematuria with prostatitis.
• If patient is hypercholesterolemic, consider 
thyroid panel to rule out hypothyroidism. • If 
patient is hypercalcemic, consider parathyroid 
hormone assay.
IMAGING
• Abdominal radiography documents 
severity of colonic impaction. Other findings 
may include colonic or rectal foreign body, 
colonic or rectal mass, prostatic enlarge -
ment, fractured pelvis, dislocated hip, or 
perineal hernias. • Pneumocolon (after 
enemas to clean colon) may better define 
intraluminal mass or stricture. 
• Ultrasonography may help define 
extraluminal mass and prostatic disease.
Colonoscopy may be needed to identify a 
mass, stricture, or other colonic or rectal 
lesion; rectal/colonic mucosal biopsy 
specimens should always be obtained.
Dependent on underlying disease process.
 TREATMENT
• Remove or ameliorate any underlying cause 
if possible. • Discontinue any medications 
that may cause constipation. • May need to 
treat as inpatient if obstipation and/or 
dehydration present.Constipation and Obstipation

324  Blackwell’s Five-Minute Veterinary Consult  
CNURSING CARE
Dehydrated patients should receive IV 
(preferably) or SC balanced electrolyte 
solutions (with potassium supplementation if 
indicated).
ACTIVITY
Encourage activity.
DIET
Dietary supplementation with a bulk-forming 
agent (bran, methylcellulose, canned 
pumpkin, psyllium) is often helpful, though 
they can sometimes worsen colonic fecal 
distension; in this instance, feed a low-residue 
diet.
• Feed appropriate diet and encourage 
activity. • Survey cat boxes daily to ensure 
level of defecation activity.
• Manual removal of feces through the anus 
with the animal under general anesthesia 
(after rehydration) may be required if enemas 
and medications are unsuccessful. • Subtotal 
colectomy may be required with recurring 
obstipation that responds poorly to assertive 
• Emollient laxatives—docusate sodium or 
docusate calcium (dogs: 50–100 mg PO 
q12–24h; cats: 50 mg PO q12–24h). 
• Stimulant laxatives—bisacodyl (5 mg/
animal PO q8–24h). Ensure that animal is 
not obstructed prior to use of stimulant 
laxatives. • Saline laxatives—isosmotic 
mixture of polyethylene glycol and poorly 
absorbed salts; usually administered as a 
trickle amount via nasoesophageal tube over 
6–12h. • Disaccharide laxative—lactulose 
(1 mL/4.5 kg PO q8–12h to effect). • Warm 
water enemas may be needed; a small 
amount of mild soap or docusate sodium 
can be added but is usually not needed; 
sodium phosphate retention enemas (e.g., 
Fleet®) are contraindicated because of their 
association with severe hypocalcemia. 
• Suppositories can be used as a replacement 
for enemas; use glycerol, bisocodyl, or 
docusate sodium products. • Motility modifiers can be administered—cisapride 
(dogs: 0.3–0.5 mg/kg PO q8–12h; cats: 
2.5–10 mg/cat PO q8–12h) may stimulate 
colonic motility; indicated with early 
megacolon.
• Lubricants such as mineral oil and white 
petrolatum are not recommended because of 
the danger of fatal lipid aspiration pneumonia 
due to their lack of taste. • Fleet (sodium 
phosphate) enemas. • Anticholinergics. 
• Diuretics.
Cisapride and cholinergics—can be used with 
caution; contraindicated in obstructive 
processes. Avoid the use of metoclopramide 
because it does not affect the colon.
N/A
• Ranitidine causes contraction of colonic 
smooth muscle in vitro. • Misoprostol causes 
contraction of colonic smooth muscle in 
vitro. • Newer-generation cisapride-like drugs 
may be available soon. • One recent pilot 
study using multistrain probiotic SLAB51® 
showed clinical improvement in a feline 
cohort having chronic constipation and 
idiopathic megacolon.
 FOLLOW-UP
Monitor frequency of defecation and stool 
consistency at least twice a week initially, then 
weekly or biweekly in response to dietary 
and/or drug therapy.
Keep pet active and feed appropriate diet. 
Subcutaneous fluids to ensure hydration can 
help reduce frequency of constipation, 
particularly in cats.
• Chronic constipation or recurrent 
obstipation can lead to acquired m  egacolon. 
• Overuse of laxatives and enemas can 
cause diarrhea. • Colonic mucosa can be 
damaged by improper enema technique, 
repeated rough m  echanical breakdown of 
feces, or ischemic necrosis secondary to 
pressure of hard feces. • Perineal irritation and ulceration can lead to fecal 
• Fair to good prognosis with early diagnosis 
and intervention. • Recurring bouts of 
constipation/obstipation may occur 
d ependent on underlying cause.
Vomiting—with severe/prolonged 
obstipation.
N/A
N/A
N/A
SYNONYMS
• Colonic impaction. • Fecal impaction.
SEE ALSO
Megacolon
Chandler M. Focus on nutrition: dietary 
management of gastrointestinal disease. 
Compend Contin Educ Vet 2013, 
35(6):E1–E3.
Rossi G, Jergens A, Cerquetella M, et al. 
Effects of a probiotic (SLAB51™) on clinical 
and histologic variables and microbiota of 
cats with chronic constipation/megacolon:  
a pilot study. Benef Microbes 2018, 
9:101–110.
Tam FM, Carr AP , Myers SL. Safety and 
palatability of polyethylene glycol 3350 as 
an oral laxative in cats. J Feline Med Surg 
2011, 13(10):694–697.
Author  Albert E. Jergens
available onlineConstipation and Obstipation  (continued)

Canine and Feline, Seventh Edition  325
C
  BASICS
OVERVIEW
• Irritant and allergic contact dermatitis—rare 
syndromes with similar clinical signs but 
different pathophysiology; differentiation may be 
more conceptual. • Irritant contact dermatitis 
(ICD)—direct damage to keratinocytes by 
exposure to particular irritant or sensitizer 
induces inflammatory response directed at skin 
without prior sensitization. • Allergic contact 
dermatitis (ACD)—type IV (delayed) hypersen -
sitivity: immunologic event requiring sensitiza -
tion and elicitation; Langerhans cells and 
keratinocytes interact with environmental 
haptens to create antigens, leading to sensitiza -
tion of T-lymphocytes and activation following 
reexposure with release of cytokines (mainly 
tumor necrosis factor alpha • [TNF- α], 
IL1βGM-CSF). • Recent reports blur 
distinction between ICD, ACD, and atopic 
• ICD—Any age as direct result of irritation 
from offending chemical. • ACD—older dogs; 
chronic exposure to antigen (months to years); 
extremely rare in cats, (except exposure to 
d-limonene-containing insecticides). • ACD—
German shepherd dog, poodle, wirehaired fox 
terrier, Scottish terrier, West Highland white 
terrier, Labrador and golden retriever.
SIGNS
Lesions
• Location determined by antigen contact; 
commonly limited to glabrous skin and 
regions frequently in direct contact with the 
environment. • Extreme erythroderma stops 
abruptly at hairline. • Initial erythema, 
edema, and papules leading to crusts and 
excoriations; lichenification and hyperpigmen -
tation with chronicity; vesicles uncommon.
Others
• Localized reactions to topical medications.
• Generalized reactions to shampoos or 
insecticide sprays. • Pruritus—moderate to 
severe (most common). • Seasonal incidence 
may indicate plant or outdoor antigen.
• Reported offending substances—plants, 
mulch, cedar chips, fabrics, rugs, carpets, 
plastics, rubber, leather, nickel, cobalt, 
concrete, soaps, detergents, floor waxes, epoxy 
resin, carpet and litter deodorizers, herbicides, 
fertilizers, insecticides (including topical flea 
treatments), flea collars, topical preparations 
(neomycin). • Increased incidence with 
atopic disease.  DIAGNOSIS
• Hypersensitivity dermatitis. • Drug reaction. 
• Pelodera dermatitis. • Hookworm d  ermatitis. 
• Pyoderma. • Malassezia  dermatitis. 
• Demodicosis. • Solar dermatitis. • Thermal 
injuries. • T rauma from rough surfaces.
• ACD—closed-patch test (corticosteroids 
and nonsteroidal anti-inflammatory drugs 
[NSAIDs] must be discontinued for 3–6 
weeks); materials taken from environment or 
home applied to upper thorax skin under 
bandage; examine for erythema, edema, 
pruritus at 48, 72 hours, and 7 days. 
• ICD—eliminate exposure to contact irritant 
or antigen, followed by provocation. • Open 
patch test—apply substance to inside pinnae; 
monitor for mild erythema, edema, pruritus; 
examine daily for 5–15 days. • Human patch 
test kits (TRUE Test®). • Skin biopsy.
• Intraepidermal vesiculation and spongiosis; 
superficial dermal edema with perivascular 
mononuclear cell infiltrate in ICD and ACD; 
polymorphonuclear cell infiltrate in ICD; 
leukocyte exocytosis common. • Lymphocytic 
spongiotic or eosinophilic and lymphocytic 
spongiotic infiltrate with intraepidermal 
eosinophilic pustules in canine ACD.
  TREATMENT
• Eliminate offending substance(s). • Bathe 
with hypoallergenic shampoos to remove 
antigen from skin. • Create mechanical 
barriers, if possible—socks, shirts, restriction 
from environment.
• Prednisolone (1 mg/kg PO q24h for 5–7 
days, then q48h for 2 weeks). • Topical 
corticosteroids for focal lesions. • Topical 
tacrolimus. • Pentoxifylline (10–25 mg/kg 
PO q8–12h initially). • Cyclosporine 
(modified, 5 mg/kg q24h).
Pentoxifylline—do not administer with 
alkylating agents, cisplatin, or amphotericin B; 
cimetidine may increase serum levels of 
pentoxifylline.  FOLLOW-UP
Remove offending substances from the 
environment.
ICD
• Acute condition—may occur after only one 
exposure; can be manifested within 24 hours of 
exposure. • Corticosteroids rarely helpful. 
• Lesions resolve 1–2 days after irritant removal.
ACD
• Requires chronic exposure for hypersensitivity 
to develop. • Reexposure results in development 
of clinical signs within 1–5 days; signs may 
persist for several weeks. • Responds well to 
corticosteroids; pruritus returns after discon -
tinuation if antigenic stimulus persists. 
• Hyposensitization not effective. • Prognosis—
good if allergen is identified and removed, 
otherwise poor: may require lifelong treatment.
• ACD = allergic contact dermatitis.
• ICD = irritant contact dermatitis.
drug.
• TNF- α = tumor necrosis factor alpha.
Ho KK, Campbell KL, Lavergne SN. Contact 
dermatitis: a comparative and translational 
review of the literature. Vet Dermatol 2015; 
26:314–327.
Author  Liora Waldman
ResnickContact Dermatitis

326  Blackwell’s Five-Minute Veterinary Consult  
C
  BASICS
• Acute inflammatory disorder involving the 
axons and myelin of nerve roots, spinal 
nerves, and peripheral nerves in dogs, with or 
without a previous history of contact with 
raccoon saliva, vaccination, or a gastrointesti -
nal or respiratory infection. • Proposed 
animal model for Guillain-Barré syndrome in 
humans.
• Etiology uncertain, appears to be immune 
mediated. • Immune-mediated inflammation 
develops 7–14 days after antecedent event 
(delayed hypersensitivity reaction?). 
• Thought to be the dog’s immune system 
reaction to a cross-reacting antigen (suspect 
molecular mimicry phenomenon between 
external antigen and gangliosides from dog’s 
neural tissue, with the development of 
antiganglioside autoantibodies). • Coonhound 
paralysis (CHP)—antecedent event is recent 
contact with raccoon saliva. • Acute canine 
idiopathic polyradiculoneuritis (ACIP)—
affected dogs with identical clinical signs to 
those with CHP but without a history of 
raccoon exposure; may have history of recent 
respiratory or gastrointestinal infection. 
• Postvaccinal polyradiculoneuritis—ante -
cedent event is recent vaccination (rare). 
• Toxoplasma gondii  infection—dogs with 
ACIP more likely to have positive titers than 
control dogs (possible triggering factor?).
• Peripheral nervous system—most severe 
involvement in the ventral (motor) nerve 
roots and ventral root components of the 
spinal nerves; lumbosacral nerve roots 
affected more severely than cervical and 
thoracic nerve roots. • Cranial nerves—nerve 
VII often affected; nerves IX, X occasionally 
affected. • Respiratory failure—secondary to 
intercostal and/or phrenic nerve involvement 
in some patients.
GENETICS
No proven basis.
• Most commonly recognized acute poly  - 
neuropathy in dogs. • Low incidence.
• CHP—relative to distribution of raccoons 
(e.g., North and Central America; parts of 
South America). • ACIP—worldwide.
Species
Dog, very occasionally cat.Breed Predilections
• CHP—Coonhounds; any breed in contact 
with raccoons susceptible. • ACIP , postvac-
cinal polyradiculoneuritis—none.
N/A
N/A
SIGNS
• Appear 7–14 days after contact with 
raccoon saliva (bite or scratch), receipt of 
vaccination, or development of respiratory or 
gastrointestinal infection. • Initial signs—
stiff, stilted gait in all limbs, typically starting 
in the pelvic limbs and eventually progressing 
to the thoracic limbs. • Rapid progression 
(2–4 days) to a flaccid, lower motor neuron 
tetraparesis to tetraplegia. • Owners may 
notice loss or change of voice. • Appetite and 
water consumption—usually normal. 
• Urination and defecation—normal. 
• Progressive phase of the disease—clinical 
signs can continue to worsen up to 5–10 days 
after onset.
• Usually symmetric. • Stiff, stilted gait that 
usually progresses rapidly to lower motor 
neuron tetraparesis or tetraplegia; some dogs 
may remain ambulatory tetraparetic. 
• Generalized hyporeflexia to areflexia, with 
the exception of a normal perineal reflex. 
• Generalized hypotonia to atonia, severe 
neurogenic muscle atrophy. • Affected dogs 
often show inability to hold the head up. 
• Aphonia or dysphonia common; no 
megaesophagus. • Facial paresis—bilateral 
incomplete palpebral closure in some 
patients. • Respiration—labored in severely 
affected dogs; occasional progression to 
respiratory paralysis. • Pain sensation intact; 
hyperesthesia common—may reflect variable 
dorsal nerve root inflammation. • Motor 
dysfunction—always predominates; even 
tetraplegic patient can usually wag its tail. 
• Mental status, urination, and defecation—  
unaffected.
CAUSES
• CHP—contact with a raccoon; perhaps more 
important, contact with raccoon saliva. 
• ACIP—none proven; possibly previous 
respiratory or gastrointestinal viral or bacterial 
infection. • Postvaccinal polyradiculoneuritis—
recent vaccination (rare).
• CHP—coonhounds tend to be predisposed 
primarily because of the nature of their activities; 
previous disease does not confer immunity and 
may increase risk of redevelopment; multiple 
bouts not uncommon. • ACIP—unknown.  DIAGNOSIS
• Other acute polyneuropathy (i.e., paraneo-
plastic neuropathy). • Distal denervating 
disease. • Botulism. • Tick bite paralysis. 
• Fulminant myasthenia gravis. • Black 
widow spider bite envenomation, coral snake 
envenomation. • Intoxications (lasalocid, 
blue-green algae). • Generalized (diffuse) or 
multifocal myelopathy (involving both 
cervical and lumbosacral intumescences).
• Serum immunoglobulins (Ig)—high serum 
IgG but not IgM in some patients. 
• Immunologic—serum reaction to raccoon 
saliva on ELISA; dogs with CHP have a strong 
positive reaction that decreases in intensity 
over time; dogs without disease but with 
raccoon contact have a strong positive reaction; 
dogs with ACIP but with no raccoon contact 
have a negative reaction. • Immunologic—for 
dogs with ACIP , identification of anti-GM2 
ganglioside antibodies reached a diagnostic 
sensitivity of 60% and a specificity of 97%.
IMAGING
Thoracic radiographs and abdominal 
ultrasound—normal.
Cerebrospinal Fluid Analysis
• Lumbar—high protein without an increase 
in leukocytes at all stages of disease. • Albumin 
leakage across the disrupted blood–nerve 
barrier of the affected ventral nerve roots is the 
primary cause of the protein increase.
Electrodiagnostics
• Electromyography (EMG)—generalized 
spontaneous activity (fibrillation potentials 
and positive sharp waves) consistent with 
denervation; EMG normal in first 4–5 
days. • Markedly low compound muscle 
action potential amplitudes after motor 
nerve stimulation. • F waves (late waves 
that indicate proximal motor nerve and 
ventral nerve root function)—prolonged 
minimum latencies, increased F ratio, 
decreased amplitudes. • Motor nerve 
conduction velocities—usually normal; 
severely affected patients may have mildly 
decreased values. • Sensory nerve func -
tion—usually normal. • Abnormalities 
provide evidence of severe peripheral motor 
axonopathy (more severe in proximal 
portions of nerves and ventral nerve roots), 
along with demyelination in the proximal 
motor nerves and ventral nerve roots.Coonhound Paralysis (Acute Polyradiculoneuritis)

Canine and Feline, Seventh Edition  327
• Ventral nerve roots and the ventral root 
components of the spinal nerves—most 
severe lesions, various degrees of axonal 
degeneration, paranodal and segmental 
demyelination, and leukocyte infiltration 
(predominantly monocytes and macrophages). 
• Peripheral nerves—affected to a lesser 
degree; might be normal. • Dorsal nerve 
roots—much less severely affected.
 TREATMENT
• Inpatient—closely monitor patients in the 
progressive phase of the disease (especially during 
first 5 days) for respiratory problems. • Severe 
respiratory compromise—mechanical ventilation 
as required. • IV fluid therapy—administer if 
patient is dehydrated. • Outpatient—once 
patient is stable and the progressive phase of the 
disease is over.
• Patients are usually able to eat and drink; 
hand feed in sternal position until able to 
reach food and water. • Intensive physical 
therapy—important to decrease muscle 
atrophy; severe neurogenic muscle atrophy is 
inevitable. • Frequent turning and excellent 
padding—essential to prevent pressure sores.
ACTIVITY
Encourage as much movement as possible.
DIET
• No restrictions. • Make sure patient is able to 
reach food and water. • Cervical weakness—may 
need to hand feed patient in sternal position.
• Inform client that good nursing care is 
essential. • Discuss importance of prevent -
ing pressure sores and urine scalding and of 
limiting the degree of muscle atrophy by 
frequent daily physical therapy (passive limb 
movement, swimming as the patient’s 
strength begins to improve). • Patient needs 
soft bedding that must be kept free of urine 
and feces, frequent turning (every 3–4 
hours), frequent bathing, and adequate 
nutrition.SURGICAL CONSIDERATIONS
N/A
• None proven effective. • Immunoglobulin—  
1 g/kg IV daily for 2 consecutive days, 0.5 g/
kg IV daily for 3 consecutive days, or 0.4 g/kg 
IV daily for 5 consecutive days; given early 
may shorten recovery time in ACIP .
Corticosteroids—do not improve clinical signs 
or shorten course of disease; may reduce survival 
in humans with Guillain-Barré syndrome.
Monitor for possible adverse reactions 
(anaphylaxis, hematuria) after IV immuno-
globulin administration.
 FOLLOW-UP
• Outpatient—keep in close contact with 
client regarding complications or changes in 
the patient’s condition. • Urinalysis—perform 
periodically to check for cystitis in tetraplegic 
or severely tetraparetic patients. • Ideally, 
reevaluate at least every 2 weeks.
• CHP—if possible, avoid contact with 
raccoons. • Postvaccinal polyradiculoneuritis—if 
strong association with a specific vaccination, 
avoid that particular vaccine in the future.
• Respiratory paralysis—in progressive phase 
of disease. • Pressure sores, urine scalding, 
cystitis—common in chronically recumbent 
dogs.
• Signs stabilize once progressive phase of 
disease is over. • Most affected dogs recover 
fully over 3–6 weeks; severely affected cases 
may take up to 3–4 months to recover; 
incomplete recoveries can happen.  MISCELLANEOUS
N/A
N/A
N/A
Unknown effect on the fetuses of an affected 
bitch.
SYNONYMS
Coondog paralysis.
SEE ALSO
• Botulism.
• Myasthenia Gravis.
• Polyneu  ropathies (Peripheral Neuropathies).
• ACIP = acute canine idiopathic 
polyradiculoneuritis.
• CHP = coonhound paralysis.
• EMG = electromyography.
Añor S. Acute lower motor neuron tetraparesis. 
Vet Clin North Am Small Anim 2014, 
44:1201–1222.
Cuddon PA. Electrophysiologic assessment of 
acute polyradiculoneuropathy in dogs: 
comparison with Guillain-Barré syndrome in 
people. J Vet Intern Med 1998, 12:294–303.
Cummings JF , de Lahunta A, Holmes DF , 
Schultz RD. Coonhound paralysis: further 
clinical studies and electron microscopic 
observations. Acta Neuropathol 1982, 
56:167–178.
Hirschvogel K, Jurina K, Steinberg TA, et al. 
Clinical course of acute canine polyradicu-
loneuritis following treatment with human 
IV immunoglobulin. J Am Anim Hosp 
Assoc 2012, 48:299–309.
Northington JW, Brown MJ. Acute canine 
idiopathic polyneuropathy: a Guillain-
Barré-like syndrome in dogs. J Neurol Sci 
1982, 56:259–273.
Author  Paula Martín Vaquera(continued)  Coonhound Paralysis (Acute Polyradiculoneuritis)

328  Blackwell’s Five-Minute Veterinary Consult  
CCopper Associated Hepatopathy
  BASICS
• Severe hepatic accumulation of copper (Cu) 
causes acute or chronic hepatitis leading to 
cirrhosis or death from liver failure.
• Mild to moderate hepatic Cu accumulation 
augments oxidative injury and increases risk for 
liver disease caused by other hepatobiliary insults, 
notably hepatotoxicity from nonsteroidal 
anti-inflammatory drugs (NSAIDs).
• Primary copper associated hepatopathy  
(CuAH) depicts copper accumulation in the 
absence of other liver disorders or as the major 
cause of liver injury .
• Secondary CuAH  depicts Cu accumulation 
caused by severe chronic cholestasis in cats 
(not dogs) or fulminant hepatic failure (rare).
• Genetic primary CuAH —only proven in 
Bedlington terriers.
• Acquired primary CuAH —most common 
canine cause of CuAH, reflects dietary Cu 
availability in commercial dog food that 
exceeds individual’s tolerance limit.
• Congenital primary CuAH  (no gene mutation 
characterized)—comparatively rare in cats.
• Some animals with primary CuAH 
accumulate Cu without histologic evidence of 
liver damage despite vacillating liver enzyme 
activity (alanine aminotransferase [ALT] most 
common); in absence of inflammation or 
hepatocyte necrosis, the term hepatopathy  is 
most correct.
• Hepatic Cu homeostasis involves complex 
regulatory system including protein transporters, 
chaperones, membrane receptors, intracellular 
binding proteins, canalicular egress pumps; Cu 
absorbed from small intestine, stored in liver, 
with excess excreted in bile.
• A single gene mutation ( COMMD1 ) causes 
genetic primary CuAH in Bedlington terriers.
• More commonly, canine hepatic Cu 
accumulation reflects Cu intake exceeding 
capacity to maintain neutral Cu balance; 
suspected pharmacogenetic basis.
• Secondary CuAH reflects reduced 
canalicular Cu egress associated with severe 
cholestasis (cats only) or severe panlobular 
liver injury (fulminant hepatic failure, rare).
• Primary CuAH—hepatocyte cytosolic Cu first 
accumulates in zone 3 (centrilobular region).
• Secondary CuAH (cats)—hepatocyte 
cytosolic Cu accumulates in zone 1 
(periportal) or adjacent to injured regions.
• Hepatic Cu concentrations widely variable—
primary CuAH: range 500 to >10,000  μg/g 
dry weight liver (DWL); secondary CuAH in 
cats rarely exceeds 1,000  μg/g DWL.
• Cu accumulation causes oxidative membrane 
injury—cell and organelles; high hepatic Cu 
concentration not always associated with 
histologic evidence of liver injury.• Focal hepatitis initiated by Cu may progress 
to chronic hepatitis, eventually cirrhosis.
• Rarely, acute severe hepatic necrosis releases 
Cu into systemic circulation causing 
hemolysis and/or acute-onset acquired 
Fanconi syndrome (proximal renal tubular 
injury causing euglycemic glucosuria).
• Hepatobiliary—centrilobular hepatitis, 
chronic hepatitis, eventual cirrhosis.
• Hemic/lymphatic—hemolytic anemia rare 
sequel to acute hepatic necrosis in dogs.
• Renal—rare reversible Fanconi syndrome 
causes euglycemic glycosuria, granular casts, 
± clinicopathologic evidence of compromised 
renal function.
GENETICS
• Autosomal recessive COMMD1  mutation in 
Bedlington terriers reduces biliary Cu excretion.
• Gene mutations remain unproven in other 
breeds and in cats; gene associations may 
modify susceptibility in Labrador retrievers, 
but no genetic test and liver biopsy remains 
gold standard for diagnosis of CuAH.
• Predisposition to CuAH recognized in 
Labrador retriever, West Highland white terrier, 
Doberman pinscher, Dalmatian, keeshond, 
corgi, Staffordshire terrier, and other breeds.
• Bedlington terrier—at one time up to 2/3 of 
dogs carried COMMD1  mutation; incidence 
significantly declined with genetic testing.
• Prevalence of excess hepatic Cu remains high 
in West Highland white terrier, Labrador 
retriever, Doberman pinscher, and other breeds.
• CuAH currently most common cause of 
chronically increased ALT activity in dogs 
(since mid-1990s) likely caused by increased 
Cu availability in manufactured dog foods.
• CuAH comprises ≥20% of liver biopsy 
submissions for abnormal enzyme activity 
in dogs.
• Primary congenital CuAH occurs in cats 
but comparatively rare.
Reported worldwide.
Species
Dog and cat; more common in dog.
Bedlington terrier, West Highland white 
terrier, Labrador retriever, Doberman 
pinscher, Dalmatian, Welsh corgi, keeshond, 
Staffordshire terrier with observed increased 
incidence of high hepatic Cu concentrations; 
no canine breed exempt.
• Bedlington terrier—Cu slowly accumulates 
to max at ∼6 years of age; dogs can be 
clinically affected at any age; most present as 
middle-aged to older dogs with chronic 
hepatitis.• West Highland white terrier—maximum 
Cu accumulation observed by 12 months of 
age and may vacillate or decline with clinical 
disease at any time; however , some dogs with 
high hepatic Cu survive to old age (15 years) 
without evidence of liver injury.
• Labrador retriever, Doberman pinscher, 
Dalmatian, other breeds—young adult to 
middle-aged at diagnosis for chronic hepatitis.
• Doberman pinscher—often develop 
hepatitis with ALT increases and Cu 
accumulation at 1–3 years of age; clinical 
signs of liver disease often recognized by 5–7 
years of age.
None
SIGNS
• Primary CuAH—4 categories:
◦ no clinical signs;
◦ subclinical disease: increased ALT activity 
with no clinical illness;
◦ acute disease associated with severe acute 
hepatic necrosis;
◦ chronic progressive hepatitis eventually 
evolving cirrhosis.
• Secondary CuAH accompanies feline 
cholestatic necroinflammatory liver disease 
(cholangiohepatitis) or rarely in dogs with 
fulminant liver necrosis.
• Acute signs—with extreme hepatic Cu 
accumulation, sudden-onset lethargy, anorexia, 
vomiting; may have rapid course, dogs 
succumb despite intensive supportive care.
• Chronic signs—variable, intermittent 
lethargy, hyporexia, weight loss, vomiting, 
diarrhea, with later polydipsia and polyuria; 
eventual liver injury leads to ascites, 
jaundice, bleeding tendencies, hepatic 
• Acute signs—lethargy, weakness, jaundice, 
pallor (anemia), vomiting, diarrhea, dark 
urine (bilirubinuria); rare hemoglobinemia 
and hemoglobinuria if intravascular 
Cu-mediated hemolysis.
• Chronic signs—weight loss, ascites, 
jaundice, nodular microhepatia; melena and 
petechial hemorrhage in animals with 
significant panlobular injury.
CAUSES
• Genetic primary CuAH—single gene 
mutation in Bedlington terriers.
• Acquired primary CuAH—either 
Bedlington mutation or suspected 
pharmacogenetic differences involving 
regulatory pathways influencing Cu 
homeostasis, making them intolerant to 
current levels of dietary Cu supplementation.
• Secondary acquired CuAH—necroinflamm  - 
atory chronic cholestatic liver disease in cats 
or diffuse severe panlobular injury in dogs or 
cats (rare).

Canine and Feline, Seventh Edition  329
CRISK FACTORS
• Primary—feeding diets or providing water 
with Cu concentrations exceeding individual’s 
tolerance to maintain neutral Cu balance.
• Stress or concurrent illnesses may precip -
itate acute illness in dogs with hepatocyte Cu 
accumulation.
• Asymptomatic dogs with primary CuAH 
may become symptomatic when additional 
disease processes or toxicities (e.g., NSAID 
administration; CCNU chemotherapy) 
impose oxidative challenge, expose hepato -
cytes to inflammatory cytokines, or another 
primary liver disease develops.
  DIAGNOSIS
• Acute diseases—infectious (e.g., infectious 
canine hepatitis, leptospirosis, septicemia, 
suppurative bacterial cholangiohepatitis), 
acute hepatic necrosis, hepatic abscess, 
drug- or toxin-induced hepatic injury, acute 
pancreatitis, hepatic lymphoma, immune-
mediated hemolytic anemia, zinc toxicity.
• Chronic diseases—chronic hepatitis or 
cholangiohepatitis of any other cause, drug- 
or toxin-induced liver injury, severe diffuse 
glycogen-type vacuolar hepatopathy (dogs), 
infectious hepatitis, chronic obstructive 
biliary disease, chronic fibrosing pancreatitis, 
congenital portosystemic shunt, primary or 
metastatic hepatic neoplasia.
• CBC—may be normal; regenerative 
anemia, leukocytosis, neutrophilia if acute 
Cu-associated hemolysis; microcytic or 
normocytic, normochromic nonregenerative 
anemia in chronic progressive liver injury; 
microcytosis usually reflects acquired 
portosystemic shunting.
• Biochemistry —increased liver enzymes 
(ALT, aspartate transaminase [AST], 
γ-glutamyl transferase [GGT], and alkaline 
phosphatase [ALP] with increase in ALT > 
ALP); hyperbilirubinemia in dogs with severe 
liver injury; increased ALT without clinical 
signs increases suspicion for early or cyclic 
CuAH necrosis.
• As hepatic function deteriorates—onset of 
hypoalbuminemia, ± hyperglobulinemia, low 
blood urea nitrogen (BUN), hypoglycemia, 
hypocholesterolemia.
• Urinalysis —usually normal, bilirubinuria 
escalates with hyperbilirubinemia; hepatic 
insufficiency: dilute urine, ammonium 
biurate crystalluria reflects acquired porto -
systemic shunts (APSS); glucosuria, granular 
casts if acquired Fanconi syndrome.
• High fasting or postprandial total serum 
bile acid (TSBA) values—dogs with severe liver injury, remodeling, or portal hyper -
tension associated with APSS.
• Prolonged prothrombin time (PT), 
activated partial thromboplastin time 
(APTT), activated clotting time (ACT), 
mucosal bleeding time in severe liver injury.
• Rare increased serum Cu concentration—
dogs with acute severe CuAH liver necrosis; 
otherwise serum Cu does not reflect liver Cu 
concentrations; low-yield screening test.
• Hepatic Cu measurements must be 
reconciled with histopathologic findings.
• Genetic marker testing in Bedlington 
terrier—microsatellite markers or specific 
COMMD1  mutation; however, kindreds of 
Bedlington terriers with CuAH have had 
negative PCR-based gene tests.
IMAGING
• Radiography—unremarkable in most dogs; 
small liver in chronic hepatic injury, poor 
abdominal detail if ascites.
• Ultrasonography—early: normal hepatic 
imaging; later: hyperechoic to heterogeneous 
nodular echogenicity; ascites in some cases.
• Liver biopsy —gold standard diagnostic test; 
confirms and characterizes liver injury; needle 
samples may not provide adequate liver lobe 
assessment as Cu is differentially distributed 
across lobes and liver sections; biopsy at least 
3 lobes.
• Routine H&E staining—can overlook 
pathologic Cu accumulation.
• Cu-specific staining—rhodanine (preferred); 
confirms Cu-protein aggregates, details zonal 
distribution.
• Semi-quantitative scoring system—
estimates severity of Cu accumulation; 
variation among interpreters confounds 
comparisons between biopsy reports.
• Cu measurements—can be completed on 
fresh, frozen, formalin fixed liver, liver tissue 
extracted from paraffin blocks, or liver sections.
• Distribution of hepatocytes with cytosolic 
Cu granules and quantification of Cu should 
be reconciled—areas of dense fibrosis, 
parenchymal extinction, regenerative nodules 
contain lower Cu concentrations than 
unremodeled liver tissue; this phenomenon 
causes discordance between measured and 
assessed Cu accumulations.
• In dogs with severe illness with high risk for 
general anesthesia and liver biopsy, hepatic 
aspiration cytology with samples stained with 
rhodanine may identify Cu accumulation; 
qualitative with variable accuracy; not 
recommended method for definitive diagnosis.
Cu Measurement
• Atomic absorption spectroscopy —gold 
standard method of Cu determination; 
requires at least full needle biopsy (≥16 g) 
sample; larger samples improve accuracy.
• Cu must be expressed per DWL.• Digital scanning of rhodanine-stained biopsy 
sections —validated against atomic absorption 
spectroscopy, accurately quantifies liver Cu 
(Cornell University) on biopsy sections; 
allows rhodanine staining of all sections to 
determine accurate hepatic Cu distribution 
and quantification.
Hepatic Cu Concentrations (DWL)
• Normal hepatic Cu ≤400  μg/g.
• Hepatic Cu concentration in dogs with 
primary diet-induced or genetic CuAH ( μg/g 
DWL)—Bedlington terrier ( COMMD1  
mutation): 850–12,000; West Highland white 
terrier: up to 3,500; Labrador retriever: 
400–9,000; Doberman pinscher: 1,000–10,000; 
Dalmatian: 750–22,000; cat: 700–8,000.
• Avoid  analytic methods “estimating” sample 
hydration or reporting Cu on wet weight basis.
• Cu accumulates in lysosomes and 
mitochondria in zone 3 (centrilobular) 
hepato  cytes in dogs.
• Oxidative injury—mechanism of hepato -
cellular injury.
• In some cases, apparent immune-mediated 
hepatitis accompanies CuAH injury.
• Rhodanine Cu staining confirms affiliation 
of Cu with histologic injury.
• Histologic features commonly include 
formation of “copper granulomas” in areas of 
hepatocyte necrosis—reflects response to 
oxidatively mediated hepatocyte necrosis; 
adjacent copper-laden hepatocytes.
• Chronic untreated necroinflammatory 
injury progresses to chronic hepatitis, 
parenchymal extinction, liver fibrosis, 
eventually to cirrhosis and formation of 
APSS.
• CuAH causing necroinflammatory liver 
injury leads to development of microhepatia, 
regenerative nodules, fibrotic “firm” liver 
texture.
  TREATMENT
• Outpatient for most dogs.
• Inpatient evaluation and treatment for dogs 
with hepatic failure or severe acute hepatitis.
• See Hepatitis, Chronic; Cirrhosis and 
Fibrosis of the Liver for detailed management 
of liver disease.
• Animals in liver failure require fluid and 
electrolyte correction; may require treatment for 
HE and coagulopathies and should be treated 
with IV N-acetylcysteine (NAC) for oxidative 
injury, d-penicillamine chelation protocol 
started as soon as oral treatment possible.
• Dogs with hemolytic anemia may require 
whole or packed red blood cell (RBC) 
transfusion, IV NAC.(continued)  Copper Associated Hepatopathy

330  Blackwell’s Five-Minute Veterinary Consult  
C• Dogs with acquired Fanconi syndrome 
require IV fluid therapy and IV NAC to 
protect against acute renal failure.
ACTIVITY
Normal; rest if severe acute hepatic necrosis.
DIET
• Feed Cu-restricted diets to all affected dogs 
for their lifetime .
• Merely feeding Cu-restricted diet is unreliable 
intervention for dogs with pathologic hepatic 
Cu accumulation (see Suggested Reading).
• Avoid Cu in water if copper pipes—run 
water for 5 min to remove eluted Cu; restrict 
access to water with Cu >0.2 ppm.
• Prescription-type liver diets contain lowest 
Cu content, only provide 2.2–2.5 g protein/
kg body weight when fed for maintenance 
energy requirements; however , dietary protein 
content should only be reduced  for dogs 
exhibiting signs of HE or developing 
• Supplemental protein added to base 
prescription “liver” diets to increase protein 
intake by 0.5 g up to 1.5 g protein/kg body 
weight using low Cu-containing foods; select 
supplemental low Cu-containing protein 
sources using USDA food tables (freely 
available on internet).
• Alternative dietary management—balanced 
homemade Cu-restricted diets ( avoid  organ 
meats, nuts, certain grains) formulated by 
veterinary clinical nutritionist.
• Supplement water-soluble vitamins but 
avoid ascorbate (vitamin C supplements) 
during Cu hepatotoxicity as may augment 
oxidative injury.
• Avoid mineral supplements containing Cu 
if homemade diet; use specifically formulated 
supplements (e.g., Balance-It ®).
• Chelation protocol must be adjunctively used 
with commercial diets for initial Cu removal.
• Educate all Bedlington terrier owners about 
genetic basis of CuAH in this breed and 
appropriate genetic testing, but inform that 
some dogs require liver biopsy for diagnosis.
• Other breeds—monitor for increased ALT 
activity with liver biopsy.
• Dogs receiving NSAIDs with circumstantial 
increase in ALT activity should be investigated 
for potential asymptomatic or “silent” hepatic 
Cu accumulation.
• Dietary management and chronic inter  - 
mittent chelation or zinc administration 
needed for life in most dogs rescued from 
CuAH.
• Animals with hepatic failure are surgical 
and anesthetic risks.
• Hypoxia encountered during anesthesia or 
surgery can provoke Cu-driven oxidative injury.  MEDICATIONS
See other liver topics for specific treatments of 
chronic hepatitis and cirrhosis.
Chelation
d-Penicillamine
• 10–15 mg/kg PO q12h on empty stomach 
(1h before feeding); bioavailability reduced 
50% if given with food.
• Mechanism—chelates Cu, promotes urinary 
excretion of Cu, other Cu-protective effects.
• Supplement vitamin B6 (pyridoxine)— 
25 mg PO q24h for duration of d-penicillamine 
• Initiate treatment in dogs with increased 
ALT activity associated with biopsy-
confirmed centrilobular Cu accumulation in 
>25% centrilobular hepatocytes or that 
reconciles with lobular injury/remodeling and 
Cu affiliation.
• Hepatic Cu as low as 600  μg/g DWL may 
require chelation and chronic management.
• Dogs with hepatic Cu <1,500  μg/g DWL 
usually cleared with 6 months of d-penicillamine 
chelation based on cases with biopsy-proven 
response.
• Dogs with hepatic Cu >3,000  μg/g may 
require ≥9–12 months chelation or longer.
• Drug-associated vomiting or hyporexia—
abated with starting ½ dose d-penicillamine 
and titrating upward or concurrent low-dose 
prednisone; giving with morsel of meat 
anecdotally reported to solve nausea but may 
compromise drug bioavailability.
• Monitoring—most clinicians use ALT as 
surrogate marker because of cost and risks 
associated with follow-up liver biopsy; 
post-treatment biopsy optimal.
• Expect substantial decline in ALT by 8 
weeks of chelation; do not discontinue daily 
chelation until ALT within normal range for 
several months, coordinating with anticipated 
chelation duration based on hepatic biopsy 
Cu quantification.
• Successful chelation achieves remarkable 
histologic improvement and resolution of 
ALT activity.
Trientine hydrochloride
• Alternative Cu chelator—as effective as 
d-penicillamine with similar guidelines; dose: 
5–7 mg/kg PO q12h given 1h before meals; 
higher dosing associated with acute renal injury.
• T rientine currently restrictively expensive 
and difficult to acquire.
• Ammonium tetrathiomolybdate—
alternative method for chelating Cu in 
circulation, from liver, and blocking enteric 
uptake in humans with Wilson’s disease; 
limited use in dogs.Zinc—Blocking Enteric Cu Uptake
• Zinc oral administration may assist in 
chronic control of CuAH; zinc use predicated 
on study of only 6 dogs.
• Reduces intestinal Cu absorption—study 
demonstrated reduced hepatic Cu concen -
trations after 2 years.
• 100 mg elemental zinc PO q12h 1h before 
feeding as loading dose for 2 months, then 
25–50 mg PO q12h for Bedlington terrier-sized 
dog; zinc acetate best tolerated as zinc source.
• In humans, zinc therapy less effective  than 
chelation for chronic management.
• May be useful in early CuAH with lower 
hepatic Cu concentrations: <1,000  μg/g DWL.
• Effects too slow to achieve therapeutic 
utility in dogs with high Cu concentrations 
and hepatitis where chelation therapy required 
for acute Cu mobilization and elimination.
• Coadministration of zinc and Cu strongly 
contraindicated  as will negate efficacy of each 
• Vomiting and inappetence commonly 
associated with zinc-induced gastritis.
• Evidence suggests low zinc utility in CuAH 
in dogs—low concentrations of oral zinc 
concurrent with Cu-restricted diet in previously 
chelated Labrador retrievers provided no 
additional benefit (see Suggested Reading).
• d-α-tocopherol (vitamin E)—10 U/kg 
q24h PO; may be mixed in food.
• S-adenosylmethionine (SAMe)—20 mg/kg 
q24h, given on empty stomach.
• Silibinin (milk thistle extract, form bound 
to phosphatidylcholine [PPC] improves 
bioavailability)—5 mg/kg PO q24h; no 
proven benefit aside from high-dose IV 
silibinin for Amanita toxicity.
• Ursodeoxycholic acid—10–15 mg/kg PO 
divided BID given with food for best 
bioavailability (see Hepatitis, Chronic).
• Polyunsaturated PPC 
(dilinolylphosphatidylcholine [DLPC])— 
20–50 mg/kg PO q24h (soy bean extract; 
PhosChol ® form providing 52% DLPC) 
mixed with food, advised for membrane-
protectant and antifibrotic effects; apparent 
benefit with described chelation protocol 
based on post-treatment biopsy evaluations.
• Ascorbic acid (vitamin C) may augment Cu 
hepatotoxicity.
• Avoid treatment with NSAIDs in affected 
dogs.
• Remain aware of altered drug metabolism 
related to reduced first-pass extraction if 
APSS develop or altered hepatic metabolism/
biotransformation in dogs with severe centri  - 
lobular necrosis and remodeling.
• Avoid NSAID administration.Copper Associated Hepatopathy  (continued)

Canine and Feline, Seventh Edition  331
CPOSSIBLE INTERACTIONS
Penicillamine or trientine may not be 
effective if giving concurrent zinc therapy.
  FOLLOW-UP
• Liver enzymes initially q2–4 weeks for 8 
weeks, then q2-4 months.
• Evaluate body weight and condition.
• Optimal reassessment—hepatic biopsy with 
determination of hepatic Cu concentration 
within 1 year of initiated treatment.
• If using zinc therapy—assess serum zinc 
concentrations initially, then during first 2–3 
weeks until stable to insure values increase 
but remain within nontoxic range (200–
500 μg/dL), then q6 months; plasma zinc 
does not reflect liver zinc concentrations.
• Breed only Bedlington terriers without 
COMMD1  mutation; liver registry 
available for Bedlington terriers proven 
unaffected on basis of hepatic Cu concen -
tration <400  μg/g DWL at 1 year of age or 
by gene testing.
• Other breeds noted previously may have 
recognized kindred predispositions.
• d-Penicillamine can cause anorexia and 
vomiting; start at low end of dose range for 
first week; give 1h before meals; small amount 
of food may reduce nausea but reduces 
treatment efficacy.
• d-Penicillamine can induce glycogen-type 
vacuolar hepatopathy and ALP activity.
• d-Penicillamine side effects—glomerulo -
nephritis, polyarthritis, drug-associated 
hepatopathy, or autoimmune-like vesicular 
disease of mucocutaneous junctions that 
resolves on drug withdrawal; note: assess urine 
for proteinuria before initiating therapy; rare 
hepatotoxicity: indicated by escalation of ALT 
activity; drug known to induce ALP .
• Excess zinc (oral dose >200 mg/day or 
blood concentration >800 μg/dL) can cause 
hemolytic anemia.EXPECTED COURSE AND PROGNOSIS
• Prognosis poor in acutely affected young 
dogs with fulminant hepatic failure or older 
dogs with cirrhosis; however, some respond to 
acute care and chelation.
• Dogs with mild to moderate acute hepatic 
injury usually have good prognosis.
• Even dogs with nodular hepatopathy and 
microhepatia and ascites can respond well to 
described protocol with resolution of many 
histologic changes, including fibrosis.
• Good prognosis warranted if CuAH 
detected before liver remodeling or develop -
ment of hepatitis.
• Health evaluations that include ALT 
measurement help identify at-risk dogs.
• Important to evaluate ALT in any dog 
placed on chronic NSAIDs where Cu 
retention appears to augment centrilobular 
hepatotoxicity; measure ALT before and 2–4 
weeks after NSAID initiation (sooner if 
patient demonstrates inappetence, vomiting, 
lethargy).
• Do not breed affected Bedlington terriers or 
carriers.
• Genetics of other at-risk breeds unknown—
some kindred predispositions recognized.
SYNONYMS
• Bedlington hepatitis.
• Chronic active hepatitis.
• Chronic Cu toxicity.
• Cu toxicosis.
SEE ALSO
• APSS = acquired portosystemic shunt. 
• APTT= activated partial thromboplastin time.
• AST = aspartate transaminase.• BUN = blood urea nitrogen.
• CuAH = copper associated hepatopathy.
• DLPC = dilinolylphosphatidylcholin.
• DWL = dry weight liver.
• GGT = γ-glutamyl transferase.
• NAC = N-acetylcysteine.
drug.
• PPC = phosphatidylcholine.
• TSBA = total serum bile acid.
www.vetgen.com for genetic screening in 
Bedlington terriers
Fieten H, Biourge VC, Watson AL, et al. 
Dietary management of Labrador retrievers 
with subclinical hepatic copper accumula-
tion. J Vet Intern Med. 2015, 29:822–827.
Fieten H, Hooijer-Nouwens BD, Biourge 
VC, et al. Association of dietary copper and 
zinc levels with hepatic copper and zinc 
concentration in Labrador Retrievers. J Vet 
Intern Med 2012, 26:1274–1280.
Hoffmann G, van den Ingh TS, Bode, P , et al. 
Cu-associated chronic hepatitis in Labrador 
Retrievers. J Vet Intern Med 2006, 
20(4):856–861.
Johnston AN, Center SA, McDonough SP , 
et al. Hepatic copper concentrations in 
Labrador Retrievers with and without 
chronic hepatitis: 72 cases (1980–2010). J 
Am Vet Med Assoc 2013, 242(3):372–380.
dogs (1982-2015). J Vet Intern Med 2018, 
Acknowledgment The author and book 
Sean P . McDonough.
available online(continued)  Copper Associated Hepatopathy

332  Blackwell’s Five-Minute Veterinary Consult  
C
 BASICS
Pica is an abnormal ingestive behavior in 
which nonfood items are consumed. 
Coprophagia is a form of pica in which feces 
is consumed.
• The pathophysiology of pica is unclear.  
• Coprophagia is not usually a pathologic 
condition. • Pica is a sign that may be 
associated with a variety of different 
conditions—any medical condition leading to 
nutritional deficiencies, electrolyte imbalances, 
gastrointestinal (GI) disturbances, poly­
phagia, or CNS disturbances may lead to 
pica and/or coprophagia. • Severely calorie ­
restricted diets or imbalanced diets leading to 
insufficiencies may also lead to pica and/or 
coprophagia.
GI—foreign body obstruction, GI upset 
leading to vomiting and diarrhea; increased 
chance of GI parasitism with coprophagia.
GENETICS
• Pica—unknown. • Coprophagia—occur ­
rence has been estimated at 16–23% in dogs.
Species
Coprophagia is common in dogs but rare in 
cats. Pica is seen in both dogs and cats.
Oriental cat breeds such as Siamese may be at 
greater risk of pica.
Pica occurs more often in puppies than in 
adult dogs. Pica in cats is most likely to begin 
prior to 18 months of age.
SIGNS
• In dogs, ingestion of inappropriate items 
such as rocks, clothing, and/or feces. • In cats, 
ingestion of fabrics, plastic, shoelaces, string, 
thread, or other inappropriate items.
• Halitosis if coprophagia is the presenting 
problem. • Dental trauma if the dog targets 
hard objects. • Pallor or weakness if anemia is 
a contributing condition. • Poor body 
condition if malabsorption or maldigestion is 
a contributing condition. • Neurologic signs 
if caused by neurologic disease. • May be 
abnormalities on abdominal palpation if 
gastroenteritis or foreign body.CAUSES
Behavioral Causes
• Coprophagia is considered normal maternal 
behavior; the dam or queen licks the anogenital 
region of the neonate to stimulate elimination 
and then consumes the excreta. • Coprophagia 
may be considered a normal exploratory behavior 
in puppies; it has been postulated that high levels 
of deoxycholic acid in feces may contribute to 
neurologic development. • It is normal for dogs 
to seek out cat feces because it is high in 
protein—odor and taste may also be appealing.  
• Ungulate feces is also appealing to dogs, 
apparently due to partially digested vegetable 
matter. • Dogs described as “greedy eaters” have 
higher incidence of coprophagy; therefore a 
voracious appetite may predispose to copropha ­
gia. • Feces may be appetizing to some dogs, so 
the behavior might be self ­rewarding. • Dogs that 
have been punished for eliminating in the house 
could learn to eat their own feces in an apparent 
attempt to avoid punishment. • Dogs may also 
eat their own feces as a form of “nest cleaning.”  
• Coprophagia may be attention ­seeking behavior 
if a dog learns that it reliably leads to immediate 
owner attention. • Coprophagia may also develop 
in response to anxiety or frustration. • Pica may 
occur secondary to stealing behavior when the 
dog is highly motivated to prevent the owner 
from retrieving the stolen object or when the 
object has ingestive appeal. • Pica may develop as 
a result of anxiety or frustration that leads to 
destruction and subsequent consumption of an 
item.
Medical Causes
• Anemia. • Malnutrition leading to poly  ­ 
phagia. • Endocrinopathies—hyperthyroid ­
ism, diabetes mellitus, hyperadrenocorticism. 
• Maldigestion/malabsorption (e.g., exocrine 
pancreatic insufficiency).  
• Inflammatory bowel disease. • Small 
intestinal bacterial overgrowth. • CNS disease. 
• Portosystemic shunt. • Intestinal parasitism.
Drug-Induced Causes
Administration of drugs such as cortico­
steroids, progestins, phenobarbital, or
benzodiazepines can lead to polyphagia.
• Early weaning of kittens has been 
postulated to lead to sucking and ingestion 
of fabrics. • Cats fed low ­roughage diets 
and/or not allowed access to roughage 
sources such as grass. • Dogs lacking 
appropriately stimulating environment, 
adequate activity, or social interactions may 
be at risk for pica and/or coprophagia.  
• Long periods of confinement, especially in 
a barren environment, may predispose to 
coprophagia. • Dogs in multidog households 
may be at higher risk of demonstrating 
coprophagia. DIAGNOSIS
• Diagnosis is based on history and descrip­
tion of the behavior. • History should include: 
⚬ Description of the problem—when and 
where it happens. ⚬ Age of onset.  
⚬ Owner’s usual response, any corrections 
attempted so far, and their results. ⚬ Changes 
in household, schedule, diet, or health 
associated with onset of problem. ⚬ Feeding 
routine of pets—when, where fed, by whom. 
⚬ Any other unusual oral behaviors. ⚬ Other 
behavioral problems. ⚬ House training 
status—when and where the pet eliminates.  
⚬ How the pet was house trained. ⚬ Relationships 
with other pets. • Environment, including daily 
schedule for play, exercise, attention, or 
training. • Medical health should be 
evaluated, including appetite and weight, any 
signs of nausea or GI upset such as excessive 
lip licking or surface licking, and color, 
consistency, and frequency of feces.  
• Pica must be differentiated from destructive 
chewing, where items may be torn apart but 
not consumed. • Pica must also be differenti­
ated from instances where an animal 
consumes a nonfood item because the item 
smells and/or tastes appealing.
• Results suggesting diabetes mellitus, 
hyperadrenocorticism, hyperthyroidism, or 
drug­induced causes of polyphagia.  
• Anemia or hypoproteinemia. • Results 
suggesting presence of a portosystemic 
shunt—microcytosis, target cells, hypoalbu ­
minemia, low blood urea nitrogen (BUN), 
ammonium biurate crystalluria. • Peripheral 
eosinophilia may occur due to g  astro­
intestinal parasitism or eosinophilic 
inflammatory bowel disease.
• T rypsin ­like immunoreactivity (TLI)—may 
be low if exocrine pancreatic insufficiency 
exists. • Serum folate and cobalamin to 
evaluate for small intestinal bacterial 
overgrowth and small intestinal mucosal 
disease. • Fecal fat and fecal trypsin may help 
to evaluate for exocrine pancreatic insufficiency 
and other malabsorption/maldigestion ­related 
conditions. • Thyroid panel to determine if 
hyperthyroid. • Fecal examinations to screen 
for intestinal parasites; note: coprophagia can 
result in false ­positive tests for helminths in 
dogs. • Bile acids to evaluate for presence of a 
portosystemic shunt. • Adrenocorticotropic 
hormone (ACTH) stimulation if hyperadren­
ocorticism a consideration.Coprophagia and Pica

Canine and Feline, Seventh Edition  333
CIMAGING
Survey abdominal radiographs and/or 
abdominal ultrasonography if indicated to 
rule out foreign body obstruction. May also 
demonstrate microhepatica if a portosystemic 
shunt is present.
• GI scoping and biopsy may be needed to 
evaluate for gastric and small bowel disease.  
• Cultures if indicated to evaluate for small 
intestinal bacterial overgrowth.
 TREATMENT
Treatment of Pica
• Prevent access to nonfood items that are 
likely targets—physical barriers to prevent 
access or confine animal away from targeted 
nonfood items; teach dog to wear basket 
muzzle. • Change to diet higher in fiber.  
• Provide feeding toys and acceptable foraging 
opportunities (e.g., green plants such as grass 
or catnip for cats). • Teach dogs a “Drop it” 
or “Leave it” command so the owner can 
prevent consumption of inappropriate items. 
• If diagnosis consistent with compulsive 
disorder, see appropriate section in text for 
Treatment of Coprophagia
• Prevent access to feces. • Walk dog on 
leash and pick up feces immediately. • 
Teach dog to wear basket muzzle. • Head 
collar for increased ability to guide pet 
away from feces and reward “turning away” 
after defecation; dogs should then be 
rewarded with a tasty treat for returning to 
the owner on command. • There is no 
evidence that changing the taste or texture 
of the stool helps to decrease coprophagia 
or that any product marketed for the 
treatment of coprophagia reliably stops the 
behavior. • Taste aversion might be taught 
by treating the feces with a strongly 
distasteful substance (e.g., hot sauce, 
cayenne pepper, etc.); all feces that the dog 
can come in contact with must be treated 
in order for this to be effective; however, 
even if effective, dogs can learn to recognize 
which feces are treated, and ingest untreated 
feces.
ACTIVITY
• Increased mental and physical enrichment 
may help in treatment and prevention of pica 
and coprophagia and keep the pet engaged in 
alternative desirable activities. • Regular, 
predictable schedules of interaction and 
exercise can decrease anxiety and may aid in 
treatment of pica and coprophagia.DIET
Dietary changes may be helpful in some 
cases of coprophagia. A more highly 
digestible diet or the addition of plant ­
based enzyme supplements or meat 
tenderizers is rarely successful in decreasing 
• Owners should be counseled that copropha ­
gia is, in most cases, normal canine behavior 
and not harmful unless the dog consumes feces 
containing pathogens or infective parasites.  
• Owners should avoid the use of any form of 
direct or confrontational punishment for pica 
or coprophagia due to the risk of increasing 
anxiety, possibly worsening the behavior, and/
or leading to other problem behaviors. Close 
supervision and prevention of access are the 
best approach.
If the behavior is determined to be a 
compulsive disorder or secondary to anxiety, 
psychoactive drugs or anxiolytic drug therapy 
may be indicated.
The use of any drugs that might contribute 
to polyphagia should be avoided when 
possible.
If drugs are indicated, precautions should be 
considered for the specific drug.
If drugs are prescribed, interactions should be 
 FOLLOW-UP
• Client should be contacted in 1–2 weeks to 
verify compliance and determine if there is 
improvement. • If no or minimal improve­
ment, further diagnostics should be 
• Prevent access to the items likely to be 
consumed. • Careful supervision during 
house training may help to prevent puppy 
exploration of feces and reinforcement of 
coprophagia. • Administration of monthly 
parasiticide to control GI parasites.
Foreign body obstruction is most common 
sequela to pica in both dogs and cats.EXPECTED COURSE AND PROGNOSIS
 ∘Prognosis is guarded if the condition has 
been present for a long period of time; or the 
owner is not willing to closely supervise the 
dog when it eliminates or prevent access to 
inappropriate items that the pet attempts to 
consume. • If owner is willing to supervise 
the dog and comply with treatment 
r ecommendations, prognosis improves.
In adult or geriatric onset of pica or 
coprophagia, primary underlying medical 
conditions should be strongly suspected.
• Owners of wool ­sucking cats should be 
cautioned that the behavior appears to have 
a breed disposition, so avoiding breeding of 
this individual may be prudent and 
responsible action. • If this behavior is 
believed to be associated with a compulsive 
disorder, the animal should not be bred, as 
compulsive disorders appear to have a 
hereditary basis.
SYNONYMS
• Depraved appetite. • Wool sucking or wool 
chewing in cats.
SEE ALSO
• Compulsive Disorders—Cats.
• Compulsive Disorders—Dogs.
• Fear, Phobias and Anxieties—Cats.
• Fear, Phobias, and Anxieties—Dogs.
• TLI = trypsin ­like immunoreactivity.
Behavior, 2nd ed. Ames, IA: Wiley ­
Blackwell, 2018, pp. 436–446, 754–760.
Houpt KA. Domestic Animal Behavior, 4th 
ed. Ames, IA: Blackwell, 2005, pp. 321–334.
3rd ed. St. Louis, MO: Saunders Elsevier, 
2013, pp. 78–79, 157–158.
Author  Valarie V. Tynes
available online(continued)  Coprophagia and Pica

334  Blackwell’s Five-Minute Veterinary Consult  
C
  BASICS
• Penetrating—a wound or foreign body 
enters but does not pass through the cornea 
or sclera. • Perforating—a wound or foreign 
body completely passes through the cornea or 
sclera; greater risk of vision loss than penetrating. 
• Simple—only the cornea or sclera, 
penetrating or perforating, other eye 
structures intact. • Complicated—perforat-
ing, involves other ocular structures, uveal, 
vitreal, or retinal incarceration or prolapse 
through the wound, traumatic cataract, 
hyphema, lid lacerations.
• Sharp trauma—wounds by an outside-in 
mechanism. • Blunt trauma—wounds by an 
inside-out mechanism; eye undergoes sudden 
changes in its equatorial and axial dimensions 
and intraocular pressure (IOP); actual wound 
may be distant from point of impact; often 
more damaging than sharp trauma. • All or a 
portion of foreign object initiating injury may 
be retained in wound or eye.
• Musculoskeletal—surrounding skull or 
orbital tissue. • Nervous—brain injury.  
Common
Species
SIGNS
• Usually acute onset. • History of running 
through vegetation, hit by projectiles 
(gunshot etc.), scratched by a cat. • T rauma 
may not be observed.
• Varies with tissues affected. • Corneal, 
scleral, or eyelid deformity, edema, or 
hemorrhage. • May see retained foreign body. 
• Often rapidly seals; may appear only as 
subconjunctival hematoma. • May also see iris 
defects, pupil distortion, hyphema, cataract, 
vitreal hemorrhage, retinal detachment, and 
exophthalmia.
CAUSES
Blunt or sharp trauma.
• Preexisting visual impairment. • Young, 
naïve, or highly excitable animals. • Hunting or 
running through heavy vegetation. • Fighting. DIAGNOSIS
• T raumatic event not observed and no 
foreign body found—consider nontraumatic 
causes of ocular injury. • T raumatic hyphema—  
generally accompanied by corneal or scleral 
lesions and subconjunctival or periocular 
hemorrhage. • T raumatic cataracts— 
disrupted lens capsule. • T raumatic retinal 
detachment—accompanied by intraocular 
Normal, or related to other injuries.
• Cytologic examination and aerobic culture 
and sensitivity of the wound and foreign 
body—recommended even if infection is not 
apparent; specimen may be collected under 
general anesthesia at time of surgery. • Consider 
other tests (platelet count, coagulation profile, 
etc.) if nontraumatic causes possible.
IMAGING
• Ocular ultrasonography—if ocular media 
are opaque; may clarify extent and nature of 
intraocular disease, may detect foreign body.  
• Orbital radiographs, CT, or MRI (if 
nonmetallic)—may help determine 
projectile’s course; may detect foreign body.
• Determine nature, force, and direction of 
impact of object—to identify which tissues 
may be involved. • Do not put pressure on 
eye until rupture or laceration of globe has 
been ruled out. • Assess vision—menace 
response; aversion to bright light. • Periocular 
skin and orbit—examine for lacerations or 
deformities; suspect globe involvement if lid 
laceration crosses eyelid margin or penetrates 
orbital septum; entry sites often small and 
quickly seal. • Abnormal ocular motility—
suggests extraocular muscle trauma, orbital 
hemorrhage or edema, retained foreign 
bodies, or peripheral nerve or CNS damage.  
• Scleral rupture—consider if subconjunctival 
hemorrhage, especially if anterior chamber is 
deep or shallow, there is vitreal hemorrhage, 
or eye is abnormally soft. • Pupils—assess 
size, shape, symmetry, direct and consensual 
light reflexes. • Detailed ophthalmoscopy—
assess clarity of ocular media and fundus 
integrity, rule out intraocular foreign body.  
• Seidel test—if any question of corneal or 
scleral leaking; use a dry to slightly moist 
fluorescein strip to paint a thin coat of 
fluorescein over the surface of the defect; 
leaking aqueous combines with the orange fluorescein, forming a bright green rivulet 
(seen best with cobalt illumination).
• Depends on wound and affected tissues. 
• Usually correlates with clinical examination 
findings. • Vitreal hemorrhage—may 
organize into a fibrous band that causes 
traction retinal detachment. • Post-traumatic 
sarcoma (cats)—may occur months to years 
after severe ocular trauma.
 TREATMENT
• Depends on severity. • Outpatient—if 
integrity of globe is ensured.
• Sedation—consider for excited or fractious 
patients. • When walking—apply an 
Elizabethan collar (E-collar) and use a harness 
or put ipsilateral foreleg through the leash to 
avoid increasing IOP in affected eye.
Injuries Considered for Medical 
Treatment
• Complicated wounds, those with retained 
plant material, and those caused by blunt 
trauma with tissue devitalization—infection 
common. • Bacterial e  ndophthalmitis— 
5–7% of perforations; very rare in wounds 
that only penetrate but do not perforate the 
cornea. • Nonperforating wounds with no 
wound edge override or gape—apply an 
E-collar; give topical antibiotic or atropine 
o phthalmic solutions. • Nonperforating 
wounds with mild wound gape or shelved 
edges—apply a therapeutic soft contact lens 
and an E-collar; give topical antibiotic or 
atropine ophthalmic solutions. • Simple 
full-thickness, pinpoint corneal perforation 
with a negative Seidel test that has a formed 
anterior chamber and no uveal prolapse—
sedentary patients; use a therapeutic soft 
contact lens and an E-collar; give topical 
antibiotic or atropine ophthalmic solutions; 
reexamine a few hours after applying the lens 
and at 24 and 48 hours.
ACTIVITY
• Usually confined indoors (cats) or limited to 
leash walks until healing is complete. • A harness is 
preferred to a collar to reduce pressure on the neck 
and the risk of increased IOP and wound leaks.
Warn client that the full extent of the injury 
(cataracts, retinal detachment, infection) may 
not be apparent until days or weeks after the 
injury and that long-term follow-up is 
necessary.Corneal and Scleral Lacerations

Canine and Feline, Seventh Edition  335
CSURGICAL CONSIDERATIONS
Injuries Requiring Surgical Exploration 
or Repair
• Full-thickness corneal lacerations with a 
positive Seidel test. • Full-thickness 
wounds with iris incarceration or prolapse. 
• Full-thickness scleral or corneoscleral 
lacerations. • Suspected retained foreign 
body or posterior scleral rupture. • Simple 
nonperforating wound with edges that are 
moderately or overtly gaping and that are 
long or more than two-thirds the corneal 
thickness.
Injuries Considered for Surgical 
Exploration or Repair
• Small full-thickness corneal lacerations with 
a negative Seidel test and no uveal prolapse.  
• Large conjunctival lacerations. • Partial-
thickness corneal or scleral lacerations in an 
active patient.
• Penetrating—topical antibiotics alone (e.g., 
neomycin, polymyxin B, and bacitracin) or 
gentamicin solution q6–8h; usually sufficient. 
• Perforating wounds with negative Seidel 
test—systemic ciprofloxacin (dogs: 10–20 mg/kg 
PO q24h); topical cefazolin (add injectable 
cefazolin to artificial tears to concentration of 
33 mg/mL) and either topical ophthalmic 
ciprofloxacin or ofloxacin; both drugs q4–6h. 
• Perforating wounds with positive Seidel 
test—systemic ciprofloxacin (dogs: 
10–20 mg/kg PO q24h); topical antibiotics as 
noted above, only after defect has been made 
watertight.
Anti-Inflammatories
• Topical 1% prednisolone acetate or 0.1% 
dexamethasone solution q6–12h; as soon as 
wound is sutured or has epithelialized 
(becomes fluorescein stain negative), as long 
as infection is not present. • Systemic 
prednisone 0.5–1 mg/kg PO q12–24h; for 
sutured or epithelialized wounds when 
inflammation is severe, when lens or posterior 
structures are involved, or when wound is 
infected or not epithelialized and control of 
inflammation is mandatory to preserve the 
eye. • Topical nonsteroidal anti-inflammtory 
drugs (NSAIDs)—flurbiprofen or others; if 
topical corticosteroids are contraindicated and control of inflammation is mandatory to 
preserve the eye.
Mydriatics
1% atropine ophthalmic solution q6–12h—
when there is significant miosis.
• Topical atropine may provide sufficient pain 
relief. • Carprofen 2.2 mg/kg PO q12h or 
4.4 mg/kg PO q24h. • T ramadol—2–5 mg/kg 
PO q12h.
• Topical ophthalmic ointments—avoid in 
Seidel-positive perforations until wound closed. 
• Systemic ciprofloxacin—avoid in young dogs.
• Aminoglycosides—topical application may be 
irritating and may impede reepithelization if used 
frequently or at high concentrations; possibility 
for renal toxicity. • Topical solutions may be 
preferable to ointments if corneal integrity is 
questionable. • Atropine—may exacerbate 
keratoconjunctivitis sicca and glaucoma. • Topical 
or systemic NSAIDs—use cautiously with 
hyphema; unknown safety in cats.
Systemic NSAIDs—may potentiate nephro -
toxicity of aminoglycosides; ensure good 
hydration and adequate renal function.
Topical ciprofloxacin ophthalmic solution—
may be used instead of combination of 
topical cefazolin and fortified aminoglycoside; 
some streptococcus are resistant.
 FOLLOW-UP
• Deep or long penetrating wounds that have 
not been sutured and perforating wounds—
recheck q24–48h for first several days to 
ensure integrity of globe, to monitor for 
infection, and to check control of ocular 
inflammation. • Superficial penetrating 
wounds—usually recheck at 3–5-day intervals 
until healed. • Antibiotic therapy—alter 
according to culture and sensitivity.
• Take care when introducing new puppies to 
households with cats. • Minimize running 
through dense vegetation; owner should consider 
having bottle of saline eyewash to irrigate foreign 
debris from eye. • Minimize visually impaired 
dog’s exposure to dense vegetation.POSSIBLE COMPLICATIONS
• Loss of eye or vision. • Chronic ocular 
inflammation or pain. • Post-traumatic sar -
coma—may develop in cat eyes following trauma.
• Most eyes with corneal lacerations or a 
retained corneal foreign body are salvageable.  
• The more posterior the injury, the poorer the 
prognosis for retention of vision. • Poor 
prognosis—scleral or uveal involvement, no 
light perception, perforating injuries involving 
the lens or with significant vitreal hemorrhage 
or retinal detachment. • Penetrating injuries 
usually better prognosis than perforating 
injuries. • Blunt trauma carries poorer 
prognosis than sharp trauma.
Depends on nature and extent of 
injury.
• Systemic corticosteroids—may complicate 
pregnancy. • Systemic ciprofloxacin—should 
be avoided during pregnancy.
SEE ALSO
• Hyphema.
• Proptosis.
• E-collar = Elizabethan collar.
drug.
Ledbetter EC, Gilger BC. Diseases and 
surgery of the canine cornea and sclera. In: 
Gelatt KN, Gilger BC, Kern TJ, eds., 
IA: Wiley-Blackwell, 2013, pp. 976–1049.
Maggs DJ. Diseases of the Cornea and Sclera. 
In: Maggs DJ, Miller PE, Ofri R, eds., 
Slatter’s Fundamentals of Veterinary 
Elsevier, 2018, pp. 213–253.
available online(continued)  Corneal and Scleral Lacerations

336  Blackwell’s Five-Minute Veterinary Consult  
C
 BASICS
OVERVIEW
Acquired corneal disorder characterized by lipid 
or calcium deposition. May be unilateral or 
bilateral, have distinct margins, and occur 
secondary to other ocular or systemic disorders.
Primarily in dogs, uncommon in cats. Lipid 
deposition most common in geriatric dogs. 
May be associated with systemic hyperlipo- 
proteinemia.
SIGNS
• Lipid deposits—gray-white or crystalline; 
band-shaped, irregular, or circular. • Calcium 
deposits—dense white to crystalline; irregular, 
punctate to band-shaped lesions in the 
superficial stroma. • Frequently associated with 
inflammatory disorders such as keratitis or 
uveitis. • Corneal vascularization, edema, and 
pigmentation often present. • With progres -
sion the cornea may develop a roughened 
appearance; disruption of epithelium can lead 
to ulceration. • Associated ocular conditions 
that may lead to corneal degeneration—cor -
neal scars, keratoconjunctivitis sicca (KCS), 
exposure keratitis, chronic uveitis, episcleritis, 
phthisis bulbi, chronic topical steroid therapy, 
limbal neoplasia. • When lipid deposition 
occurs secondary to hyperlipoproteinemia, 
perilimbal annular ring may form with clear 
zone between affected cornea and limbus; 
often bilateral but may be asymmetric; 
vascularization is variable.
• Lipid—hyperlipoproteinemia may increase 
risk or worsen existing deposits; can be 
secondary to hypothyroidism, diabetes 
mellitus, hyperadrenocorticism, diet, 
pancreatitis, nephrotic syndrome, liver 
disease, hyperlipidemia of miniature 
schnauzers. • Calcium—hypercalcemia, 
hyperphosphatemia, hypervitaminosis D, 
hyperadrenocorticism, uremia. • Lipid and 
calcium deposits are frequently seen together.
  DIAGNOSIS
• Corneal scar—nonpainful lesion, gray to 
white; fluorescein negative; relatively smooth 
corneal surface; distinct margins. • Corneal 
stromal dystrophies—bilateral, often 
symmetric foci of gray to white deposition, 
distinct margins; heritable, not associated 
with ocular inflammation; do not retain 
fluorescein stain; often occur away from the 
limbus. • Edema—bluish to gray; usually homogeneous; varies in size depending on 
severity; indistinct margins; can retain 
fluorescein stain if corneal erosion/ulceration 
present. • Corneal ulcer—ocular pain, retains 
fluorescein stain, varying degrees of edema 
around the lesion. • Inflammatory cell 
infiltrates—ocular pain, gray to tan to yellow 
with indistinct margins; cytologic examination 
of cornea reveals white blood cells, 
microorganisms.
• Systemic tests only necessary if hyperlipidemia is 
suspected; no systemic tests necessary for most cases. 
• Lipid—evaluate fasting cholesterol, triglycer -
ide, blood glucose concentrations. • Calcium—
evaluate ionized calcium concentration.
Endocrinopathy testing—thyroid function, 
stimulation test.
Fluorescein staining—may retain dye around 
margins of deposit if raised.
  TREATMENT
• T reat primary ocular disease if present. 
 • Corneal deposits causing patient discom-
fort or impaired vision may benefit from 
corneal debridement or superficial keratec-
tomy followed by medical treatment; deposits 
likely to recur if underlying cause not 
corrected. • Hyperlipoproteinemia may 
resolve with low-fat diet and treatment of 
systemic disease if present; both may slow or 
stop progression of ocular disease.
• Topical broad-spectrum antibiotics (i.e., 
triple antibiotic) for ulcerated cornea; 
frequency depends on severity; usually 
uncomplicated ulcers treated q8–12h.  
• Topical nonsteroidal anti-inflammatory 
drug q8–12h—indicated if uveitis noted.  
• Topical 0.2% cyclosporine—to improve 
tear film quality, reduce inflammation.  
• Topical 1% atropine q8–24h—indicated to 
reduce pain if uveitis or ulceration is present. 
• Topical ethylene diamine tetra-acetate 
(EDTA) solution 0.5–3% q6h; may help 
minimize calcium deposits; usually used 
following debulking procedure to improve 
efficacy. • Artificial tear ointment q6–12h; 
may prevent or reduce frequency of 
secondary corneal ulceration; provides 
lubrication and improves comfort when 
corneal surface is irregular.CONTRAINDICATIONS/POSSIBLE 
COMPLICATIONS
• Topical corticosteroids—not recom-
mended, may worsen severity; contraindi-
cated with corneal ulceration. • Topical 
atropine—contraindicated with KCS, 
glaucoma, lens luxations.
  FOLLOW-UP
Monitor serum cholesterol and triglycerides 
to assess efficacy of dietary management in 
hyperlipidemic patients; monitor treatment of 
primary disease if present.
• Corneal ulceration—associated with worsening 
of disease. • Vision—may be affected in 
advanced disease; may be severe if primary 
ocular disease (e.g., uveitis) present. • Deposits 
may recur following superficial keratectomy.
SEE ALSO
• Corneal Opacities—Dystrophies.  
• EDTA = ethylene diamine tetra-acetate.
https://www.columbiaeye.org/education/
digital-reference-of-ophthalmology/
cornea-external-diseases/degenerations
Crispin SM, Barnett KC. Dystrophy, 
degeneration and infiltration of the canine 
cornea. J Small Anim Pract 1983, 
24:63–83.
Author  Kathern E. Myrna
Amber L. LabelleCorneal Opacities—Degenerations and Infiltrates

Canine and Feline, Seventh Edition  337
C
 BASICS
OVERVIEW
• Primary, inherited (or familial), bilateral, 
and often symmetric condition of the cornea 
that is not associated with other ocular or 
systemic diseases. • Three types based on 
anatomic location—epithelial: characterized 
by dyskeratotic and necrotic epithelial cells, 
focal absence of epithelial basement mem-
brane, and cell infiltrate in anterior corneal 
stroma; stromal: lipid deposition within 
corneal stroma; endothelial: characterized by 
abnormal, dystrophic endothelial cells.
Usually dogs; rare in cats.
Epithelial
Shetland Sheepdogs—age of onset 6 
months–6 years; slow progression.
Stromal
• Usually young adult dogs at age of onset.  
 • Affected breeds—Afghan hound, Airedale 
terrier, Alaskan Malamute, American cocker 
spaniel, beagle, bearded collie, bichon frisé, 
cavalier King Charles spaniel, German 
shepherd, Lhasa apso, mastiff, miniature 
pinscher, rough collie, Samoyed, Siberian 
husky, Weimaraner, whippet, and others; 
inheritance pattern identified in few breeds.
Endothelial
• Dogs—primarily Boston terriers, Chihuahuas, 
and dachshunds; may affect other breeds; 
typically middle-aged or older at onset of 
clinical signs; female predilection suggested.  
• Cats—affects young animals; described most 
often in domestic shorthairs; a similar condition 
without endothelial disease is inherited as an 
autosomal recessive disorder in Manx.
SIGNS
All cause some degree of opacity in cornea.
• Can be asymptomatic or have blepharospasm; 
multifocal white or gray circular to irregular 
opacities or rings; sometimes associated with 
multifocal corneal erosions. • Vision usually 
not affected.
Stromal
• Usually asymptomatic without inflamma-
tion. • Central—most common; gray, white, 
or silver oval to circular opacity of central or 
paracentral cornea; with magnification may 
note multiple fibrillar to coalescing opacities 
that have crystalline or ground-glass 
appearance (crystalline corneal dystrophy).  
• Diffuse—affects Airedales; more diffuse, 
dense opacity than with central dystrophy.  
• Annular—commonly affects Siberian 
huskies; doughnut-shaped opacity of paracentral or peripheral cornea. • Vision—
usually not affected; visual deficit possible 
with advanced or diffuse disease.
• Asymptomatic in early stages. • Edema of 
temporal or inferio-temporal cornea that usually 
progresses to entire cornea after months to years. 
• Corneal epithelial bullae (bullous keratopathy) 
and subsequent corneal erosion ulceration may 
develop; erosions or ulceration may cause 
blepharospasm due to pain. • Vision—may be 
impaired with advanced disease.
• Epithelial—result of degenerative or 
innate abnormalities of corneal epithelium 
and/or basement membrane. • Stromal—
innate abnormality or localized error in 
corneal lipid metabolism; may be affected by 
hyperlipoproteinemia (may increase opacity). 
• Endothelium—degeneration of endothelial 
cell layer; subsequent loss of endothelial cell 
pump function results in corneal edema.
 DIAGNOSIS
• Epithelial, stromal—other causes of corneal 
opacity: corneal degenerations, ulcers, scars, 
inflammatory cell infiltrates. • Endothelial—
other causes of diffuse corneal edema: uveitis 
and glaucoma.
Epithelial, stromal—high concentrations of 
cholesterol and triglyceride levels may modify 
course of disease, but are not the cause.
• Stromal—usually does not retain fluores-
cein stain. • Epithelial or endothelial—may 
retain fluorescein stain, often in multifocal 
punctate areas, particularly with advanced 
disease. • Tonometry—to eliminate glaucoma 
as cause of corneal edema.
 TREATMENT
• Advanced epithelial or endothelial disease 
with ulceration—may require treatment for 
ulcerative keratitis. • Stromal—usually none 
required; may perform superficial keratec -
tomy to remove lipid deposits if severe, but 
usually unnecessary and deposits may recur.  
• Inform client that some corneal dystrophies 
are inherited. • Advanced endothelial 
dystrophy—may use therapeutic soft contact 
lens with or without debridement of 
redundant corneal epithelial tags, conjunctival 
flap surgery, or thermal cautery of cornea. MEDICATIONS
• Corneal ulceration—topical antibiotics and 
possibly atropine (see Keratitis—Ulcerative). 
• Epithelial—1–2% cyclosporine in oil or 
0.2% ointment q8–24h to relieve clinical 
signs. • Endothelial—topical 5% sodium 
chloride ointment; palliative treatment; does 
not markedly clear cornea, but may prevent 
progression and rupture of corneal epithelial 
bullae.
Topical corticosteroids—no benefit to lipid 
(stromal) dystrophy, of questionable benefit 
to other forms of dystrophy.
 FOLLOW-UP
• Reexamination—necessary only if 
ocular pain or corneal ulceration develops. 
• Corneal opacity—may wax and wane 
with lipid dystrophy; unlikely to resolve. 
• Corneal ulceration—may accompany 
progression of epithelial or endothelial 
dystrophy. • Vision—not substantially 
affected except in advanced cases.
SEE ALSO
• Corneal Opacities—Degenerations and 
Infiltrates.
24:63–83.
Author  Ellison Bentley
Consulting Editor  Kathern E. MyrnaCorneal Opacities—Dystrophies

338  Blackwell’s Five-Minute Veterinary Consult  
C
 BASICS
OVERVIEW
• A focal, light brown to black, plaque-like 
area of stromal coagulation necrosis usually 
located axially.
• Usually caused by chronic corneal ulcer  - 
ation, trauma, or exposure.
• Synonym—keratitis nigrum.
• Cats—any breed, age.
• Brachycephalic breeds, Siamese predisposed.
• Colorpoints may be genetically 
SIGNS
• Unilateral or bilateral, focal round to oval, 
variably sized areas of corneal discoloration 
ranging from translucent golden-brown 
(early) to opaque black (chronic).
• Often with chronic nonhealing corneal 
ulcer.
• Corneal vascularization and edema.
• History of feline herpesvirus-1 (FHV-1) 
keratoconjunctivitis.
• Blepharospasm or ocular discharge.
• Conjunctival hyperemia and chemosis.
• Miotic pupil.
• May be static for long periods or may 
rapidly progress.
• With chronicity, corneal vascularization 
may extrude plaque.
• Thought to involve chronic mechanical 
corneal irritation or ulceration with corneal 
necrosis and desiccation.
• Risk factors include chronic corneal 
ulceration, chronic trichiasis or entropion, 
brachycephalic conformation, lagophthalmia, 
keratoconjunctivitis sicca (KCS), qualitative 
tear film disorders (lipid or mucin deficiency), 
FHV-1 infection, topical corticosteroids, and 
iatrogenic trauma (grid keratotomy).
 DIAGNOSIS
• Corneal perforation/iris prolapse—protrud-
ing iris is fleshy and yellow to light brown.
• Corneal foreign body.
• Corneal pigmentation—rare in cats.
• Corneal neoplasia—melanocytoma occurs 
at limbus and is typically nonpainful.
No specific abnormalities.
• Schirmer tear test—very low values suggest 
KCS, but some normal cats have low values.
• Corneal culture and cytology to rule out 
corneal infection.• Fluorescein stain.
• Tear film breakup time (TBUT)—normal 
time to breakup of fluorescein-stained tear 
film is 21 seconds; TBUT may be decreased 
in cats with sequestra or FHV-1 due to mucin 
tear film deficiency or secondary to corneal 
disease.
• Corneal histopathology—confirm diagnosis 
and evaluate completeness of excision.
• PCR for FHV-1— limited value.
• Conjunctival biopsy—goblet cell numbers 
may decrease with conjunctival inflammation 
or FHV-1.
  TREATMENT
• Lesion depth, degree of ocular pain, and 
cost are important factors.
• Medical—supportive care, wait for 
sequestrum to spontaneously slough; ocular 
pain may persist for months and sloughing of 
sequestrum may lead to deep corneal 
ulceration or perforation.
Surgical Considerations
• Lamellar keratectomy—if performed early, 
can relieve ocular pain, promote corneal 
healing, and may prevent lesion from 
involving deeper corneal stroma.
• Corneal grafting should be performed if 
≥50% of corneal stroma has been excised; 
options include conjunctival pedicle grafting, 
grafting with synthetic, autogenous, or 
heterologous biomaterials, and corneoscleral 
transposition.
• Diamond burr debridement may be used to 
remove superficial sequestra.
• Postoperative management—broad-
spectrum topical antibiotic, atropine 
ointment, and tear supplement.
• Topical oxytetracycline with polymyxin B 
or bacitracin-neomycin-polymyxin B q6–8h 
(prophylactic).
• Topical 1% atropine sulfate ointment 
q12–24h (improve ocular comfort).
• Topical lubricants (e.g., carboxymethylcel-
lulose gel) q6–8h (reduce mechanical 
irritation and corneal desiccation); may 
prevent progression of nonulcerated 
sequestra.
• Topical or systemic antiviral therapy in cats 
with history or clinical signs of FHV-1 
Topical antibiotics (neomycin) may be 
irritating and cause chemical conjunctivitis.  FOLLOW-UP
• If managing medically, examine as needed 
to monitor progression and for complications 
associated with sloughing of sequestrum.
• If managed by keratectomy, examine q5–7 
days until corneal defect has reepithelialized 
(usually 7–14 days).
• Sequestra may recur or occur in contra -
lateral eye; recurrence more likely in cats with 
low Schirmer tear tests, full-thickness lesions, 
or in cases in which keratectomy did not 
result in complete excision of pigmented 
corneal tissue or predisposing cause was not 
addressed.
Corneal perforation may occur if sequestrum 
sloughs, leaving full-thickness defect, or if 
sloughing results in deep stromal corneal 
ulcer that becomes malacic or infected.
• Corneal ulceration—cats.
• Eyelid conformational abnormalities 
(trichiasis, entropion, etc.).
• FHV-1 = feline herpesvirus-1.
• TBUT = tear film breakup time.
Featherstone HJ, Sansom J. Feline corneal 
sequestra: a review of 64 cases (80 eyes) 
from 1993 to 2000. Vet Ophthalmol 2004, 
7(4):213–227.
Gilger BC, Kern TJ, eds., Veterinary 
Ophthalmology, 5th ed. Ames, IA: Wiley, 
2013, pp. 1495–1496.
Author  Anne J. Gemensky Metzler
Consulting Editor  Kathern E. MyrnaCorneal Sequestrum—Cats

Canine and Feline, Seventh Edition  339
CCough
  BASICS
• A sudden and often repetitively occurring 
defense reflex that helps clear large airways of 
excess secretions, irritants, foreign particles, 
and microbes, or clear foreign material from 
upper airways. • The cough reflex consists of 
three phases: inhalation, forced exhalation 
against a closed glottis, and violent expulsion 
of air from the lungs following opening of the 
glottis, usually accompanied by a sudden 
noise. Coughing can happen voluntarily as 
well as involuntarily, although in dogs and cats 
it is presumed to be essentially involuntary. 
Coughing should not be confused with other 
airway sounds (cf differential diagnosis).
• A physiologic reflex in healthy animals that 
protects the lower airways from inhalation of 
foreign particles and helps clear particles that 
have been entrapped in the mucus; acts in 
conjunction with the mucociliary clearance 
mechanism. • The cough pathway includes 
cough receptors, which are made up of sensory 
nerves in the airways, the vagus nerve, the central 
cough center, and effector muscles. • The cough 
pathway can be stimulated by mechanical or 
chemical factors; endogenous triggers include 
airway secretions and inflammation; exogenous 
triggers include smoke and aspirated foreign 
material. • Cough receptors include rapidly 
adapting stretch receptors (sensitive to 
mechanical stimuli) that are located within the 
mucosa of the tracheobronchial tree (especially 
larynx and trachea), and pulmonary/bronchial 
C-fibers, which are more sensitive to chemical 
stimulation; coughing mechanisms and 
pathways are very complex and are not fully 
understood, even in humans.
• Respiratory—cough of any origin can be an 
inciting factor for aggravation or precipitation 
of signs associated with tracheal collapse in 
susceptible breeds. • Cardiovascular—
enlargement or impaired function of the right 
ventricle can result from a respiratory disorder 
causing tissue damage, hypoxic injury, and/or 
chronic hypoxic pulmonary vasoconstriction 
(cor pulmonale).
• Dogs and cats of all ages and breeds. • Much 
more common clinical sign in dogs than in 
cats. • Cough of tracheal origin is less common 
in cats than in dogs. • Age, breed, and sex 
predispositions vary with inciting cause.
SIGNS
• Cough must be differentiated from similar 
signs such as reverse sneezing, gagging, 
retching. • Description of the cough and/or 
smartphone recording of suspect sounds are 
helpful in identification of the anatomic structures involved in dogs (i.e., honking 
cough is typical of tracheal collapse, harsh 
sonorous cough followed by terminal retch 
characterizes cough of tracheal or bronchial 
origin, faint moist cough is heard in moderate 
to severe pneumonia). • Cough can be 
described as dry or moist, productive, honking, 
short or harsh, faint or sonorous, followed by 
gagging or retching. • Cough can be elicited 
by traction on the collar (laryngeal or tracheal 
origin), aggravated by exercise or excitation 
(tracheal collapse), or can occur after a period 
of rest (cough due to heart failure). • Can be 
accompanied by stertor or stridor (laryngeal, 
tracheal origin) or dyspnea (many areas).
CAUSES
Upper Respiratory Tract Diseases
• A variety of sinonasal conditions cause 
extension of inflammation and/or secretions 
into the pharynx and/or larynx and can lead 
to the upper airway cough syndrome (UACS), 
previously referred to as postnasal drip 
syndrome. • Laryngeal and/or pharyngeal 
disease (inflammation, paralysis, tumor, 
granuloma, collapse). • T racheal disease 
(inflammation, infection, foreign body, 
collapse, stenosis, tumor).
Lower Respiratory Tract Diseases 
(Tracheobronchial or Bronchopulmonary 
Disease)
• Inflammatory (feline bronchitis syndrome; 
dogs: chronic bronchitis, eosinophilic broncho  - 
pneumopathy). • Infectious—bacterial, viral 
(dog: distemper, kennel cough; cat: feline 
leukemia virus [FeLV], feline immuno -
deficiency virus [FIV], feline infectious 
peritonitis [FIP], calicivirus, herpesvirus), 
parasitic (dog: Filaroides  spp., Angiostrongylus 
vasorum , Capillaria aerophilia , Crenosoma 
vulpis ; cat: Aerulostrongylus abstrusus ; dog, cat: 
Paragonimus kellicotti , Dirofilaria immitis ), 
protozoal (cat: toxoplasmosis; dog: pneumo -
cystosis), fungal (blastomycosis, histoplasmosis, 
coccidiomycosis, cryptococcosis, aspergillosis). 
• Neoplastic (primary, metastatic, compression 
due to enlarged lymph nodes). • Chemical or 
traumatic (aspiration, near drowning, noxious 
fumes, foreign body, trauma, hemorrhage). 
• Chronic disorders of unknown origin 
(interstitial pulmonary fibrosis).
Other Diseases
• Cardiovascular diseases (pulmonary edema, 
left atrial enlargement, heart-base tumor, 
embolism). • Gastroesophageal reflux. 
• Compression of respiratory structures by 
adjacent organs (cardiomegaly, megaesophagus, 
hilar lymph node enlargement). 
• Noncardiogenic pulmonary edema (multiple 
causes). • Passive smoking inhalation. • Adverse 
drug reaction—potassium bromide in cats.RISK FACTORS
Breed
• Toy and miniature breeds at risk for 
tracheal collapse. • Terrier breeds at risk for 
pulmonary fibrosis. • Husky, Rottweiler, 
Labrador, and Jack Russell terrier at risk for 
eosinophilic bronchopneumopathy. • Giant 
breeds at risk for dilated cardiomyopathy. 
• Labrador retriever, large breeds at risk for 
laryngeal paralysis. • Siamese cats at risk for 
feline bronchitis syndrome.
Environmental Factors
Longhaired cats that are infrequently 
groomed will periodically retch, cough, and 
vomit up mats of hair.
Drugs
Potassium bromide in cats.
Geographic Area (or Travel History)
Certain diseases are common in specific areas 
(e.g., dirofilariasis, angiostrongylosis).
  DIAGNOSIS
• Similar signs. • Coughing may be confused 
with other signs such as sneezing, reverse 
sneezing, gagging, panting, retching, and 
vomiting; presence of terminal retch is often 
misinterpreted as vomiting. • Honking noise 
coughing in case of severe tracheal collapse 
can be descried by owners as severe stertor.
Minimum database may suggest acute 
bacterial infection (leukocytosis with left 
shift) or eosinophilic airway disease (periph-
eral eosinophilia).
• Filter test for microfilaria and/or heartworm 
antigen serology—for heartworm disease. 
• Serum antibody titer—toxoplasmosis, FIV, 
FIP , distemper, Angiostrongylus vasorum . 
• Coagulation profile—for any patient that 
presents with cough associated with either 
epistaxis or hemoptysis. • Feces examination 
(Baermann test: identification of 
Angistrongylus  (dogs), Aerulostrongylus  (cat), 
or other parasites ( Filarial , Crenosoma ). 
• PCR diagnosis available for several 
microorganisms. • Tests for evaluation of 
possible hyperadrenocorticism (potentially 
causing pulmonary thromboembolism).
IMAGING
• Thoracic radiographs are first step prior to any 
additional test—provide essential information 
about intrathoracic airways, lung parenchyma, 
pleural space, mediastinum, and cardiovascular 
system. • Thoracic computed tomography is 
being more and more often used for 
identification of respiratory intrathoracic 
problems. • Fluoroscopy—helpful to investigate

IMAGING
problems. • Fluoroscopy—helpful to investigate 
diseases in which dynamic obstruction is

340  Blackwell’s Five-Minute Veterinary Consult  
Csuspected (tracheal collapse, bronchial collapse, 
bronchomalacia). • Echocardiography—helpful 
when heart failure or dysfunction is suspected. 
• Thoracic ultrasonography—in case of pleural 
effusion or when a pulmonary or mediastinal 
mass is suspected.
• Endoscopy allows visualization of both static 
(tumor, granuloma, abnormal mucosa, 
excessive secretions) and dynamic (laryngeal 
paralysis, dynamic airway collapse) airway 
abnormalities. • When bronchial and/or 
alveolar infiltrates are present—samples from 
lower airways can be obtained for diagnostic 
purpose (cytology, bacterial/mycologic cultures) 
by bronchoalveolar lavage or tracheal wash. 
• T ransthoracic (fine-needle aspiration) biopsy 
or thoracoscopy—allows biopsy sample when 
interstitial infiltration is prominent. 
• Thoracocentesis—allows sampling of 
pleural fluid, can be performed under ultra  - 
sonographic guidance. • Pulse oximetry and 
blood gas determination. • Pulmonary 
function tests—require sophisticated material 
and/or experienced technicians, not readily 
available in private practice.
 TREATMENT
• Usually treated as outpatient. • Most 
successful management of cough involves 
treatment and resolution of underlying cause 
rather than use of medications that suppress 
signs. • If chronic cough is related to acute or 
chronic inflammation, anti-inflammatory 
therapy preferred to cough suppressant therapy. 
• Use of cough suppressant therapy must be 
limited to cases in which the cause of the 
cough can neither be treated medically nor 
resolved, and in which excessive coughing leads 
to exhaustion of the patient or insomnia of the 
owners, as well as aggravation of the disease.
Antimicrobial Therapy
Indicated for tracheo-broncho-pulmonary 
disease of bacterial origin. Better selected 
based in culture and antimicrobial suscepti-
bility testing. 
Anti-inflammatory Therapy
• Indicated in feline bronchitis syndrome, 
canine chronic bronchitis, or canine 
eosinophilic bronchopneumopathy. • Oral 
prednisolone 0.5 mg/kg q12h in dogs and 
cats, then taper the dose progressively to 
q48h. • Nebulized fluticasone or budesonide 
100–200  μg q12h with metered dose inhaler 
including spacer with face mask and inspira  - 
tory valve.Antitussives
• Hydrocodone (dog only)—0.2–0.3 mg/kg 
PO q 6–12h. • Butorphanol (dog only)—
0.25–1.1 mg/kg every 8–12h. • No 
antitussive available for cats. • In humans, 
gabapentin (neuromodulator) recently 
described to treat refractory chronic cough. 
• Gabapentin in dogs, 2–5 mg/kg by mouth 
every 8h, but unestablished efficacy.
Theophylline (for Dogs and Cats)
• Pharmacokinetics are form and species 
dependent; slow-release formulations exist. 
• Beneficial effects of theophylline include 
relaxation of bronchial smooth muscle, 
improved diaphragmatic contraction, and 
probably some anti-inflammatory effects 
but primary antitussive action not 
demonstrated. • Side effects are related to 
inotropic and chronotropic effects, as well 
as to an increase in blood pressure; can also 
cause nausea, diarrhea, arrhythmias, and 
CNS excitation.
Beta-2 Agonists (Cats Only)
• Delivered mostly via a meter dose inhaler 
(MDI); administered IV in emergency 
situations. Short-acting (salbutamol, 
terbutaline, fenoterol) or long-acting 
(salmeterol, formoterol) drugs. • May be 
administered temporarily to cause immediate 
and temporary relief, but not as long-term 
management; have limited effect. • Side effects 
include dry mouth, tachycardia, nausea; 
regular inhalation of racemic and S-albuterol 
(but not R-albuterol) induces airway 
inflammation in both healthy and asthmatic cats.
Expectorants
Guafenesin—included in some preparations 
but benefit not extensively studied or proven.
Antitussive agents are strictly contraindicated 
when cough is needed to clean the airways, 
i.e., in infectious or inflammatory airway 
disease.
See side effects of respective drugs.
Theophylline—clearance may be inhibited by 
other drugs such as fluoroquinolones, 
increasing risk of theophylline toxicity.
  FOLLOW-UP
• Acute cough must be adequately treated in 
order to avoid chronic cough, leading to 
possibly irreversible lesions. • Conditions 
leading to chronic cough sometimes can only 
be alleviated but not cured; communicate 
with client to ensure successful management 
of cough.POSSIBLE COMPLICATIONS
• Aggravation of tracheal collapse. • Progression 
toward chronic bronchitis, chronic obstructive 
pulmonary disease, lung emphysema, irrevers -
ible bronchial and parenchymal remodeling, 
bronchiectasis. • Acute severe cough might lead 
to syncope, rib fracture, or pneumothorax. 
• Right heart dysfunction.
• In dogs with anatomic disorders of inherited 
(e.g., primary ciliary dyskinesia) or congenital 
origin, signs might start early in life. • Puppies 
and kittens more likely to suffer from 
infectious disease. • Inflammatory disorders 
affect middle-aged adults. • Heart failure and 
tumors more frequent in older animals.
• Dogs affected with primary ciliary 
dyskinesia. • Possible decreased fertility (in 
male and female dogs) as cilia from urogenital 
tract and flagellated cells can be affected. 
• Proven hereditary in some breeds (Old 
English sheepdog; carrier test detection exists).
SEE ALSO
• Asthma, Bronchitis—Cats.
• Bronchitis, Chronic.
• Hypoxemia.
• Nasal Discharge.
• Pneumonia, Bacterial.
• Pneumonia, Eosinophilic.
• Sneezing, Reverse Sneezing, Gagging.
• T racheal Collapse.
• UACS = upper airway cough syndrome.
Ferasin L. Coughing. In Ettinger SJ, Feldman 
EC, Côté E. Textbook of Veterinary Internal 
Medicine, 8th ed. St. Louis, MO:  Elsevier, 
2016, 107–111.
Rozanski AE, Rush JE. Acute and chronic 
cough. In: Ettinger SJ, Feldman EC, eds., 
6th ed. St. Louis, MO: Elsevier, 2005, 
pp. 189–195.
Dominique Peeters.
available onlineCough  (continued)

Canine and Feline, Seventh Edition  341
C
 BASICS
OVERVIEW
• A non-neoplastic, noninflammatory 
proliferative disease of the bones of the head.  
 • Primary bones affected—mandibular rami; 
occipital and parietal; tympanic bullae; zygomatic 
portion of the temporal. • Bilateral symmetric 
involvement most common. • Affects musculo -
skeletal system.
• Scottish, Cairn, and West Highland white 
terrier breeds—most common. • Labrador 
retrievers, Great Danes, Boston terriers, 
Doberman pinschers, Irish setters, English 
bulldogs, bullmastiffs, Shetland sheepdogs, and 
boxers—may be affected. • Usually growing 
puppies 4–8 months of age. • No gender 
predilection. • Neutering may increase incidence.
SIGNS
• Usually relate to pain around the mouth 
and difficulty opening the mouth progres-
sively worsening. • Difficulty in prehension 
and mastication—may lead to starvation.
• Temporal and masseter muscle atrophy—
common. • Palpable irregular thickening of 
mandibular rami and/or temporomandibular 
joint (TMJ) region. • Inability to fully open jaw, 
even under general anesthesia. • Intermittent 
pyrexia. • Bilateral exophthalmos.
• Believed to be hereditary—occurs in certain 
breeds and families. • West Highland white 
terriers—autosomal recessive trait. • Scottish 
terriers—possible predisposition. • Young 
terrier with periosteal long bone disease—
monitor for disease.
  DIAGNOSIS
• Osteomyelitis—bones not symmetrically 
affected; generally not as extensive; lysis; lack 
of breed predilection; history of penetrating 
wound. • T raumatic periostitis—bones not 
symmetrically affected; generally not as 
extensive; history of trauma. • Neoplasia—
mature patient; not symmetrically affected; 
more lytic bone reaction; metastatic disease. • 
Calvarial hyperostosis—young patient: frontal, 
parietal, and occipital bones; does not involve 
mandible; may have long bone involvement.
• Serum alkaline phosphatase (ALP) and 
inorganic phosphate—may be high. • May 
note hypogammaglobulinemia or 
α2-hyperglobulinemia.OTHER LABORATORY TESTS
Serology—rule out fungal agents; indicated in 
atypical cases.
IMAGING
• Skull radiography—reveals uneven, bead-like 
osseous proliferation of the mandible or 
tympanic bullae (bilateral); extensive, periosteal 
new bone formation (exostoses) affecting one 
or more bones around the TMJ; may show 
fusion of the tympanic bullae and angular 
process of the mandible. • CT—may help 
evaluate osseous involvement of TMJ.
Bone biopsy and culture (bacterial and 
fungal)—necessary only in atypical cases; rule 
out neoplasia and osteomyelitis.
• Bone biopsy—reveals normal lamellar bone 
being replaced by enlarged coarse-fiber bone and 
osteoclastic osteolysis of periosteal or subperiosteal 
region. • Bone marrow—replaced by vascular 
fibrous-type stroma. • Inflammatory cells—  
occasionally seen at periphery of bony lesion.
  TREATMENT
• Palliative only. • Surgical excision of 
exostoses—results in regrowth within weeks.  
• High-calorie, protein-rich gruel diet—helps 
maintain nutritional balance. • Surgical 
placement of pharyngostomy, esophagostomy, 
or gastrostomy tube—considered to help 
maintain nutritional balance.
• Analgesics and anti-inflammatory 
drugs—palliative use warranted.  
(NSAIDs)—inhibit cyclooxygenase 
enzymes. • Deracoxib (1–2 mg/kg PO 
q24h, chewable). • Carprofen (2.2 mg/kg 
PO q12h or 4.4 mg/kg q24h). • Meloxicam 
(load 0.2 mg/kg PO, then 0.1 mg/kg PO 
q24h, liquid). • Grapiprant (2 mg/kg PO 
q24h). • Firocoxib (5 mg/kg PO q24h).
  FOLLOW-UP
Frequent reexaminations—mandatory to ensure 
adequate nutritional balance and pain control.
• Do not repeat dam–sire breedings that 
resulted in affected offspring. • Discourage 
breeding of affected animals.EXPECTED COURSE AND PROGNOSIS
• Pain and discomfort may diminish at 
skeletal maturity (10–12 months of age); 
exostoses may regress. • Prognosis—depends 
on involvement of bones surrounding TMJ. 
• Elective euthanasia may be necessary.
SYNONYMS
• Lion jaw. • Craniomandibular osteoarthropathy. 
• Craniomandibular osteodystrophy. • Mandibular 
periostitis. • Westie jaw. • Scotty jaw.
drug.
• TMJ = temporomandibular joint.
Franch J, Cesari JR, Font J. Craniomandibular 
osteopathy in two Pyrenean mountain dogs. 
Vet Record 1998, 142(17):455–459.
Huchkowsky SL. Craniomandibular 
osteopathy in a bullmastiff. Can Vet J 2002, 
43(11):883–885.
LaFond E, Breur GJ, Austin CC. Breed 
susceptibility for developmental orthopedic 
diseases in dogs. J Am Anim Hosp Assoc 
2002, 38(5):467–477.
McConnell JF , Hayes A, Platt SR, Smith KC. 
Calvarial hyperostosis syndrome in two 
bullmastiffs. Vet Radiol Ultrasound 2006, 
47(1):72–77.
Padgett GA, Mostosky UV. The mode of 
inheritance of craniomandibular osteopathy 
in West Highland White terrier dogs. Am J 
Med Genet 1986, 25(1):9–13.
Pastor KF , Boulay JP , Schelling SH, Carpenter 
JL. Idiopathic hyperostosis of the calvaria in 
five young bullmastiffs. J Am Anim Hosp 
Assoc 2000, 36(5):439–445.
Taylor SM, Remedios A, Myers S. 
Craniomandibular osteopathy in a Shetland 
sheepdog. Can Vet J 1995, 36(7):437–439.
Watson ADJ, Adams WM, Thomas CB. 
Craniomandibular osteopathy in dogs. Compend 
Contin Educ Pract Vet 1995, 17:911–921.
Author  Steven M. Cogar
Consulting Editor  Mathieu M. GlassmanCraniomandibular Osteopathy

342  Blackwell’s Five-Minute Veterinary Consult  
C
 BASICS
The acute or progressive failure of the 
cranial cruciate ligament (CrCL), which 
results in partial to complete instability of 
the stifle joint.
• Function of the CrCL includes passive 
constraint of the stifle joint by limiting 
internal rotation of the tibia, hyperextension 
of the stifle, and cranial displacement of the 
tibia relative to the femur. • T wo distinct 
bands—craniomedial band is taut on both 
flexion and extension of the joint (primary 
check) and caudolateral band is taut in 
extension and lax in flexion (secondary check).
• Types of injury:
⚬ Avulsion—skeletally immature animals 
in which acute load results in avulsion of 
the origin or insertion of the ligament. 
⚬ Acute (traumatic) rupture—result of 
hyperextension, limb overloading, or 
internal rotation; mid-substance tear of the 
CrCL; most common cause in cats. 
⚬ Progressive (chronic) degeneration 
pathogenesis remains elusive; decreases in 
elasticity, stress/strain energy, failure to 
maintain collagen fiber organization, and 
chondroid metaplasia—most common 
cause in dogs.
• Repetitive subclinical injury may be due to 
neuromuscular incoordination, aging, 
conformational abnormalities (excessive tibial 
plateau angle (TPA), medial luxating patella, 
narrow intercondylar notch), breed variations, 
poor muscle tone related to sedentary habits 
or limb immobilization, and possibly immune-  
mediated damage. • Complete and partial 
tears exist in varying degrees. • Untreated 
instability leads to degenerative osteoarthritic 
changes within a few weeks; severe within a 
few months. • Medial meniscal (caudal horn) 
damage occurs in 33.2–77% of cases—due to 
shearing force during drawer.
Musculoskeletal, ± neurologic.
GENETICS
Suspected
Most common cause of hind limb lameness 
in dogs; major cause of degenerative joint 
disease (DJD) in the stifle joint.
SPECIES
• All susceptible. • Rottweiler and Labrador 
retriever—increased incidence when <4 years of age. • West Highland white terrier—over -
represented affected small breed.
• Incidence increases with age >5 years. 
• Large- to giant-breed dogs may present 
earlier in life; approx. 2 years of age.
Female—neutered.
SIGNS
Severity of lameness—related to degree of 
rupture (partial vs. complete), mode of 
rupture (acute vs. chronic), occurrence of 
meniscal injury, and severity of inflammation 
and DJD. Condition and therefore lameness 
may be bilateral.
• Athletic or traumatic events—generally 
precede acute injuries. • Normal activity 
resulting in acute lameness—suggests 
degenerative rupture. • Subtle to marked 
intermittent lameness (for weeks to months)—  
consistent with partial tears that are progress-
ing to complete rupture.
• Varying degrees of lameness and joint 
effusion, pain, and/or crepitus; affected limb 
generally held in partial flexion while 
standing. • Cranial drawer test—diagnostic 
for rupture; test in flexion, normal standing 
angle, and extension. • Tibial compression 
test—cranial movement of tibia relative to 
femur when tightening gastrocnemius by 
flexing hock. • Medial periarticular thicken-
ing (medial buttress). • Presence of click or 
pop—63% accurate in detecting meniscal 
injury. • Hind limb muscle atrophy—espe-
cially quadriceps muscle group. • False-
negative drawer or compression tests with 
chronic or partial tears and in painful or 
anxious patients that are not sedated or 
anesthetized. • Earliest sign of partial rupture 
is pain on hyperextension of stifle.
CAUSES
• T rauma. • Repetitive microinjury; 
excessive stifle loading. • Progressive 
• Obesity. • Patella luxation. • Conformati -
onal abnormalities. • Excessive caudal slope 
of tibial plateau. • Narrowed intercondylar 
notch.
 DIAGNOSIS
• Puppy laxity—positive drawer motion that 
stops abruptly as CrCL is stretched taut. 
• Patella luxation (medial or lateral). • Collateral 
ligament injury, long digital extensor tendon injury. • Osteochondritis dissecans of femoral 
condyle. • Neoplasia (e.g., synovial sarcoma, 
osteosarcoma, chondrosarcoma). • T raumatic 
fractures or avulsions. • Caudal cruciate 
ligament rupture—uncommon and generally 
only seen with significant trauma.
N/A
N/A
IMAGING
• Verify secondary intra-articular changes such 
as DJD and rule out other differentials. 
• Common findings—joint effusion with 
capsular distention and effacement of 
infrapatellar fat pad; periarticular osteophytes; 
enthesiophytes; CrCL avulsion fractures; 
calcification of CrCL and/or menisci. • Cats 
commonly have mineralized menisci present 
(incidental finding). • Necessary for preopera -
tive planning with osteotomy procedures.
Alternative Diagnostic Imaging
Ultrasound and MRI—facility and operator 
dependent.
• Arthrocentesis—rule out sepsis or immune- 
mediated disease. • Arthroscopy—gold 
standard; direct visualization and magnifica-
tion of cruciate ligaments, menisci, and other 
intra-articular structures.
• Varying degrees of synovitis, cartilage 
fibrillation, and erosion. • Periarticular 
osteophyte formation. • Meniscal damage. 
• Ruptured fibers of CrCL—hyalinization; 
fibrous tissue invasion; necrosis; loss of 
parallel orientation of ligament bundles.
 TREATMENT
• Stabilization surgery—recommended; speeds 
rate of recovery; reduces degenerative changes; 
enhances function. • Conservative manage -
ment—diet, nonsteroidal anti-inflammatory 
drugs (NSAIDs), physical rehabilitation, 
weight loss; approx. 66% of patients have 
improved function over course of >1 year; 
DJD is progressive; not generally recommended.
Postsurgery—restricted activity with physical 
rehabilitation (e.g., ice packing, range-of-
motion exercises, massage, and muscle 
electrical stimulation); important for 
improving mobility and strength.
ACTIVITY
Restricted—duration depends on method of 
treatment and progress of patient.Cruciate Ligament Disease, Cranial

Canine and Feline, Seventh Edition  343
CDIET
• Weight control—important for decreasing 
load and thus stress on stifle joint. • Joint-health 
diets rich in omega-3 fatty acids and chondro -
protectants may support overall joint health.
• Regardless of treatment, DJD is common 
and progressive. • Return to full athletic 
function is possible, but requires early surgical 
intervention and rehabilitation. • Rupture of 
contralateral CrCL can occur in 37–48% of 
patients.
• No one technique has proven consistently 
superior, clinically or radiographically. • Recent 
force plate studies show slight differences 
between common techniques; dogs with tibial 
plateau leveling osteotomy (TPLO) procedure 
achieve normal limb loading faster than with 
extracapsular procedure.
Extra-articular Methods
• Wide variety of techniques that use an 
implant to mimic CrCL and restore stability; 
these techniques rely on periarticular fibrosis 
for long-term stability. • Alternative method 
includes fibular head transposition to realign 
and tension lateral collateral ligament in order 
to restrict internal rotation and cranial drawer.
Intra-articular Methods
Designed to replace CrCL anatomically with 
autografts (patellar ligament, fascia), allografts, 
xenografts, and synthetic materials.
Osteotomy Procedures
Cranial Tibial Closing Wedge Osteotomy
• Levels TPA by removing cranially based 
wedge of bone from proximal tibia and 
eliminates cranial thrust. • Held in place with 
bone plate and screws. • Can potentially 
shorten tibia and alter stifle biomechanics.
TPLO
• Rotational osteotomy of proximal tibia to level 
TPA and neutralize cranial tibial thrust. • Held 
in place with bone plate and screws. • Can 
accomplish correction for angular and torsional 
deformities.
Tibial Tuberosity Advancement
• Tibial crest osteotomy; crest is held in 
advanced position with cage and plate; bone 
graft fills defect. • Active control of cranial 
tibial displacement improved, which helps 
stabilize stifle. • Can combine technique with 
lateral transposition of tibial tuberosity to 
correct concurrent medial luxating patella.  MEDICATIONS
NSAIDs—minimize pain; decrease inflamm- 
ation.
Avoid concurrent use of corticosteroids with 
NSAIDs.
NSAIDs—gastrointestinal irritation or renal/
hepatic toxicity may preclude use in some patients.
N/A
• Chondroprotective drugs (polysulfated 
glycosaminoglycans, glucosamine, and 
chondroitin sulfate) may help reduce cartilage 
damage and improve regeneration. 
• Omega-3 fatty acid supplementation to 
reduce inflammation is recommended.
  FOLLOW-UP
Most techniques require 2–4 months of 
rehabilitation.
Avoid breeding animals with conformational 
• Subsequent meniscal injury can occur in 
6–22% of patients. • Incisional and/or 
implant-related infection. • Tibial tuberosity 
avulsion and/or fractures. • Patellar luxation. 
• Delayed bone healing (osteotomy proce-
dures). • Pivot shift—unknown clinical 
significance <2% (self-limiting).
Regardless of surgical technique, success rate 
better than 85%.
Meniscal damage.
See Pathophysiology.
N/APREGNANCY/FERTILITY/BREEDING
N/A
 SEE ALSO
• Arthritis (Osteoarthritis).
• Patellar Luxation.
• CrCL = cranial cruciate ligament.
• DJD = degenerative joint disease.
drug.
• TPA = tibial plateau angle.
• TPLO = tibial plateau leveling osteotomy.
Aragon CL, Budsberg SC. Applications of 
evidence-based medicine: cranial cruciate 
ligament injury repair in the dog. Vet Surg 
2005, 34:93–98.
Balzter WI, Smith-Ostrin S, Warnock JJ, Ruaux 
CG. Evaluation of the clinical effects of diet 
and physical rehabilitation in dogs following 
tibial plateau leveling osteotomy. J Am Vet 
Med Assoc 2018, 252:686–700.
Christopher SA, Beetem J, Cook JL. 
Comparison of long-term outcomes 
associated with three surgical techniques for 
treatment of cranial cruciate ligament 
disease in dogs. Vet Surg 2013, 
42(3):329–334.
Comerford EJ, Smith K, Hayashi K. Update 
on the aetiopathogenesis of canine cranial 
cruciate ligament disease. Vet Comp 
Orthop T raumatol 2011, 24:91–98.
Krotscheck U, Nelson SA, Todhunter RJ, 
et al. Long-term functional outcome of 
Tibial T uberosity Advancement vs. Tibial 
Plateau Leveling Osteotomy and extracap-
sular repair in a heterogenous population of 
dogs. Vet Surg 2016, 45(2):261–268.
Wucherer KL, Conzemius MG, Evans R, 
Wilke VL. Short-term and long-term 
outcomes for overweight dogs with cranial 
cruciate ligament rupture treated surgically 
or nonsurgically. J Am Vet Med Assoc 2013, 
242:1364–1372.
Author  Marian E. Benitez
available online(continued)  Cruciate Ligament Disease, Cranial

344  Blackwell’s Five-Minute Veterinary Consult  
C
 BASICS
A localized or systemic fungal infection 
caused by the environmental yeast 
Cryptococcus  spp., most commonly  
C. neoformans  and C. gattii .
• C. neoformans —grows in bird droppings 
and decaying vegetation; soil disturbance 
increases risk of infection. • Dogs and cats 
inhale the yeast and a focus of infection is 
established, usually in nasal passages; 
smaller dried, shrunken organisms may 
reach the terminal airways (uncommon). 
• There may be colonization or subclinical 
infection of nasal passages that spontane -
ously resolves. • Stomach and intestinal 
infections suggest that primary gastrointes -
tinal entry can occur. • Dissemination—
hematogenously spread via macrophages 
from nasal passages to brain, eyes, lungs, 
and other tissues; by extension to skin of 
nose, eyes, retro-orbital tissues, and draining 
lymph nodes.
• Cats—mainly respiratory (nose, nasophar-
ynx, and sinuses), skin (nasal planum), 
nervous, ophthalmic, and lymphatic. 
• Dogs—mainly skin (over nose and sinuses), 
respiratory (nasal passages, occasionally 
lungs), nervous (brain), lymphatic, and 
ophthalmic.
• Dogs—rare in United States; prevalence 
0.00013%. • Cats—7–10 times more 
common than in dogs; most common systemic 
mycoses of cats.
• Worldwide. • Some areas of southern 
California and Australia have an increased 
incidence and an outbreak has occurred on 
Vancouver Island in British Columbia, 
Canada. • C. gattii  grows well around 
eucalyptus trees.
Species
• Dogs—American cocker spaniels (United 
States), Doberman pinschers and German 
shepherd dogs (Australia) may be overrepre-
sented. • Cats—Siamese may be at increased 
risk.
• Most commonly cats and dogs <6 years of 
age. • Can occur at any age.
• Dogs—none. • Cats—males may be 
overrepresented.SIGNS
• Lethargy. • Varies depending on organ 
systems involved. • May have signs/problems 
for weeks to months.
Dogs
• Neurologic—seizures, ataxia, paresis. 
• Ocular signs—periorbital swelling, blind  - 
ness, uveitis, hyphema. • Skin ulceration. 
• Lymphadenopathy. • Respiratory—upper 
respiratory signs, labored breathing, coughing. 
• Vomiting, diarrhea, and anorexia.
Cats
• Nasal discharge and ocular signs. 
• Neurologic signs—seizures, disorientation, 
vestibular signs. • Granulomatous tissue seen 
at the nares. • Firm swellings over the bridge 
of the nose. • Lymphadenopathy. • Respiratory 
abnormalities less commonly noted.
• Mild fever—<50% of patients. • Dogs—
nasal discharge, multifocal CNS abnormali -
ties, ataxia, anterior uveitis. 
• Cats—respiratory noise (stertor), nasofacial 
swelling, ulcerated crusting skin lesions on the 
head, lymphadenopathy, neurologic abnor -
malities (behavior change, circling, vestibular 
signs, ataxia), ocular abnormalities (blindness, 
optic neuritis, retinal detachment).
CAUSES
Exposure to cryptococcal organisms and 
inability of immune system to prevent 
colonization and tissue invasion.
• Exposure to disrupted soil. • Infection with 
feline leukemia virus (FeLV) or feline immuno  - 
 DIAGNOSIS
Dogs
• Other causes of focal or diffuse neurologic 
disease—distemper, inflammatory menin-
goencephalomyelitis, infectious meningoen-
cephalitis (bacterial, rickettsial, protozoal), 
neoplasia, fungal diseases (depending on 
geography). • Nasal lesions, especially at 
mucocutaneous junction—immune-medi-
ated, neoplasia (squamous cell carcinoma). 
• Lymphadenopathy—lymphoma, fungal 
disease. • Chorioretinitis and optic neuritis—
fungal infections, distemper, neoplasia.
Cats
• Nasal disease—nasal tumors, chronic 
rhinitis, chronic sinusitis. • Ulcerative skin 
changes—bacterial infection, trauma, neoplasia 
(squamous cell carcinoma). • Ocular and 
neurologic abnormalities—lymphoma, feline infectious peritonitis (FIP), other infections 
(fungal, Toxoplasma ).
• Mild anemia in some cats. • Eosinophilia 
occasionally seen. • Chemistry usually normal.
• Latex agglutination or ELISA—detect 
cryptococcal capsular antigen in serum or 
cerebrospinal fluid (CSF); highly sensitive 
assay; most infected animals have measurable 
capsular antigen titers; magnitude of titer 
correlates with extent of infection. • May be 
less sensitive in dogs. • May be positive with 
colonization alone; antigen titers 1 : 32 or 
greater seen with fungal invasion.
IMAGING
• Nasal radiographs (cats)—soft tissue density 
material in nasal passage; bone destruction of 
nasal dorsum. • Contrast-enhanced CT or 
MRI best for identifying brain and nasal 
lesions. • Thoracic radiographs—can identify 
lower respiratory tract disease.
Dogs
Neurologic disease—additional procedures: 
cytologic examination and culture of CSF , 
other CSF infectious disease testing, 
measurement of CSF capsular antigen.
Cats
• Cytology of impression smears or aspirates of 
mucoid material from nasal passages, or biopsy 
of granulomatous tissue protruding from 
nares—characteristic yeast with large nega -
tively- staining (clear) capsule. • Aspirates of 
lymph nodes or subcutaneous swellings often 
high yield. • Sedated oropharyngeal exam—in 
patients with upper respiratory obstruction/
noise: may identify granuloma in nasopharynx 
(spay hook or endoscope to expose the mass). 
• Biopsy—skin lesions. • Cultures—confirm 
diagnosis; determine drug susceptibility.
• Gross lesions—gray, gelatinous mass produced 
by polysaccharide capsule; in nose, sinuses, and 
nasopharynx of cats; skin lesions usually 
ulcerative. • Neurologic lesions—more common 
in dogs; diffuse or focal CNS granulomas. 
• Chorioretinitis with or without retinal detach  - 
ment or optic neuritis. • Histologic response—
usually pyogranulomatous; inflammatory cell 
infiltrate may be mild as polysaccharide capsule 
interferes with neutrophil migration; organism 
characterized by capsulate yeast with narrow-
neck budding.
  TREATMENT
• Outpatient if stable. • Neurologic signs— 
may initially require inpatient supportive care.Cryptococcosis

Canine and Feline, Seventh Edition  345
C
Cats—nasal obstruction influences appetite; 
encourage to eat by offering warmed, palatable 
food.
ACTIVITY
N/A
DIET
Patients treated with itraconazole—give 
medication in fatty food (e.g., canned food) 
to improve absorption.
• Inform client that this is a chronic disease 
that requires months of treatment. • Reassure 
client that infection is not zoonotic.
Remove granulomatous masses in nasophar-
ynx to reduce respiratory difficulties.
• Fluconazole—preferred for ocular or CNS 
disease (water soluble and better penetrates 
CNS); cats: 50 mg/cat PO q12–24h; dogs: 
5 mg/kg PO q12h; most economical drug 
choice. • Itraconazole—cats: 10 mg/kg PO 
q24h; dogs: 5 mg/kg PO q12h; pellets in 
capsule can be mixed with fatty food; 
itraconazole liquid has better absorption on 
empty stomach and compounded itraconazole 
is not recommended. • Amphotericin B may 
have some advantage in severe disease at a 
dosage of 0.25 mg/kg IV q48h, given slowly 
over 3–4h, up to a total cumulative dose of 
4–16 mg/kg; monitor renal function closely. 
• Terbinafine (5 mg/kg PO q12h, 10 mg/kg 
PO q24h) effective for treatment of cats with 
resistant infections. • Flucytosine—25–50 mg/
kg PO q6h; synergistic with amphotericin B, 
may allow lower doses and decrease renal 
toxicity. Do not use as single agent.
Caution with concurrent steroid use (immuno  - 
suppression).
• T riazoles—hepatotoxicity; anorexia signals 
problems; monitor liver enzyme activities 
monthly initially. • Itraconazole—ulcerative dermatitis (differentiate from skin lesions of 
cryptococcosis); new skin lesions after disease 
is much improved should be considered a 
drug reaction. • Amph  otericin B—nephro -
toxicity; caution if patient is azotemic, but 
not absolute contraindication if life-threaten-
ing infection. • Terbinafine—monitor for 
hepatic toxicity and anorexia.
Cryptococcal organisms are prone to 
becoming resistant to antifungal treatment.
 FOLLOW-UP
• Monitor liver enzyme activities monthly 
(especially early in treatment) in patients receiving 
triazole antifungal agent. • Improvement in 
clinical signs, resolution of lesions, improvement 
in wellbeing, and return of appetite measure 
response to treatment. • Capsular antigen 
titers—after 2–3 months of treatment, titers 
should decrease if treatment is effective; if 
ineffective, try terbinafine, because organism may 
become resistant. • Continue monitoring antigen 
titers every 1–2 months during treatment and 
after discontinuing treatment. • Ideally treat until 
cryptococcal antigen titers reach zero (may take 
>2 years).
The organism is ubiquitous and cannot be 
avoided.
Patients with neurologic disease may have 
seizures and permanent neurologic deficits.
T reatment—anticipated duration 4 months 
to ≥1 year; patients with CNS disease may 
require lifelong maintenance; median time of 
successful treatment with fluconazole 4 
months; median time for itraconazole 
treatment 8 months.
N/AAGE-RELATED FACTORS
N/A
• Not considered zoonotic, but possibility of 
transmission through bite wounds. • Inform 
client that organism was acquired from the 
environment and that he or she could be at 
increased risk, especially if immunosuppressed.
O’Brien CR, Krockenberger MB, Martin P , 
et al. Long-term outcome of therapy for 59 
cats and 11 dogs with cryptococcosis. Aust 
Vet J 2006, 84:384–392.
O’Brien CR, Krockenberger MB, Wigney 
DI, et al. Retrospective study of feline and 
canine cryptococcosis in Australia from 
1981 to 2001: 195 cases. Med Mycol 2004, 
42:449–460.
Pennisi MG, Hartmann K, Lloret A, et al. 
Cryptococcosis in cats: ABCD guidelines 
on prevention and management. J Feline 
Med Surg 2013, 15:611–618.
Sykes JE, Hodge G, Singapuri A, et al. In 
vivo development of fluconazole resistance 
in serial Cryptococcus gattii isolates from a 
cat. Med Mycol 2017, 55:396–401.
T rivedi SR, Sykes JE, Cannon MS, et al. 
Clinical features and epidemiology of 
cryptococcosis in cats and dogs in 
California: 93 cases (1988–2010). J Am Vet 
Med Assoc 2011, 239:357–369.
available online(continued)  Cryptococcosis

346  Blackwell’s Five-Minute Veterinary Consult  
C
 BASICS
OVERVIEW
• Incomplete scrotal descent of one or both 
testes; most common testicular congenital 
anomaly.
• Abdominal or inguinal location for 
undescended testis or testes.
• Diagnosis usually made at 2 months of age 
(i.e., descent to scrotal position should occur 
before this time), with some exceptions of full 
descent occurring between 2 and 6 months of 
age.
• Abdominally retained testicles typically lack 
spermatozoa and have only Sertoli cells in the 
seminiferous tubules; estradiol (E2) and 
testosterone (T) can be present in normal 
systemic concentrations in affected animals.
• Unilaterally cryptorchid animals are 
typically fertile.
• Cats—purebred cats have higher incidence.
• Dogs—toy and miniature breeds at 2.7 
times greater risk than large breeds of being 
affected; high rates in miniature schnauzers 
with persistent Müllerian duct syndrome 
(PMDS).
• Incidence—rates up to 24.1% in some 
purebred dogs (compared to 2.1% in overall 
population) with 50% incidence in dogs with 
PMDS; in cats observed rates range from 1.3 
to 6.2%.
• Unilateral more common than bilateral; 
right testis retained twice as often in dogs, but 
with equal frequency in cats.
• Genetics—estimated medium level of 
heritability with multifactorial genetic basis; 
females act as genetic carriers for the trait.
SIGNS
• Absence of one, or both, testicles from the 
scrotum in a patient without history of 
castration.
• Cats—strong urine odor, tom cat marking 
behavior, presence of penile spines.
• Abdominal pain, lameness, vomiting—
increased risk exists for spermatic cord torsion 
of neoplastic, retained testes.
• Feminizing paraneoplastic syndrome—
estrogen-secreting Sertoli cell tumors produce 
feminizing signs including gynecomastia, 
symmetric alopecia of trunk and flanks, 
hyperpigmentation of inguinal skin, 
pendulous preputial sheath, prostatic 
squamous metaplasia.
• Affected males or carriers (i.e., females or 
nonaffected males of cryptorchid littermates) 
present in breeding lines.
• Carriers produce increased number of males 
per litter and increased litter size; efforts to 
eliminate cryptorchidism difficult in these 
circumstances.  DIAGNOSIS
• Bilateral—previously castrated patient.
• Unilateral—remaining abdominal or inguinal 
testis after removal of single scrotal testis.
T ransrectal prostate exam—intact males have 
pronounced prostate; prostate of larger breeds 
may be beyond reach.
• Human chorionic gonadotropin (hCG) 
or gonadotropin-releasing hormone 
(GnRH) stimulation test (differentiate 
cryptorchidism from castrated)—collect 
blood sample for baseline T analysis; 
administer 750 IU hCG IV or 50  μg 
GnRH IM; repeat sample collection for T 
analysis in 2–3 hours; twofold increase in 
T from baseline indicates presence of 
testicular tissue.
• Canine anti-Müllerian hormone concentra-
tion—increased level indicates testicular 
Sertoli cells present.
IMAGING
Ultrasonography—highly sensitive for 
identification of inguinal or abdominal testes.
  TREATMENT
• Identification and removal of undescended 
testis or testes.
• Orchiopexy—surgical tacking of retained 
testis into scrotum; results in misrepresentation 
of individual’s true phenotype and genotype.
• hCG or GnRH—little controlled evidence 
establishing efficacy or protocol; ethical 
concerns same as with orchiopexy.
• Failure to remove retained testis—increased 
risk of testicular neoplasia (13.6 times 
greater), spermatic cord torsion; 53% of 
Sertoli cell tumors and 36% of seminomas 
occur in retained testes.
To possibly induce descent of retained 
testicle:
• hCG (dogs)—100–1,000 IU IM 4 times in 
2-week period before 16 weeks of age.
• GnRH (dogs)—50–750  μg IM 1–6 times 
between 2 and 4 months of age.
• Buserelin (GnRH analogue; dogs)—10  μg, 
once weekly, for 3 doses.  FOLLOW-UP
Migration of testes into the scrotum after 4 
months is unlikely; rare after 6 months.
• Inguinal or umbilical hernia.
• Patellar luxation.
• Penile and preputial defects (e.g., 
hypospadias).
SEE ALSO
• Seminoma.
• E2 = estradiol.
• PMDS = persistent Mullerian duct 
syndrome.
• T = testosterone.
Feldman EC, Nelson RW. Canine and Feline 
Endocrinology and Reproduction. 
Philadelphia, PA: Saunders, 1987, pp. 
697–699.
Felumlee AE, Reichle JK, Hecht S, et al. Use 
of ultrasound to locate retained testes in 
dogs and cats. Vet Radiol Ultrasound 2012, 
53(5):581–585.
Khan FA, Gartley CJ, Khanam A. Canine 
cryptorchidism: an update. Reprod Dom 
Anim 2018, 53(6):1263–1270.
Little S. Feline reproduction: problems and 
clinical challenges. J Feline Med Surg 2011, 
13:508–515.
Author  Candace C. Lyman
Carlos R.F . Pinto.Cryptorchidism

Canine and Feline, Seventh Edition  347
C
 BASICS
OVERVIEW
• Cryptosporidium  spp.—apicomplexan 
protozoan causing gastrointestinal disease; 
ubiquitous in nature with worldwide 
• Infection—sporulated oocysts are ingested, 
sporozoites are released and penetrate 
intestinal epithelial cells; after asexual 
reproduction, merozoites released to infect 
other cells, sexual reproduction follows, then 
oocyst shedding.
• Prepatent period—5–10 days (cats).
• Immunocompetent animals—intestinal 
disease.
• Immunocompromised animals—intestinal, 
liver, gallbladder, pancreatic, respiratory 
• Dogs—prevalence 0.5% worldwide; 
2–17% in the United States.
• Cats—prevalence 0–29% worldwide; 
2–15% in the United States.
• Dogs—virtually all clinical cases in 
immunocompromised animals or animals <6 
months of age; older dogs can excrete oocysts 
without clinical signs.
• Cats—more common in immuno­
compromised cats or kittens <6 months of age.
SIGNS
• Most infections subclinical.
• Principally small bowel diarrhea; large 
bowel diarrhea reported.
• C. canis  (dogs), C. felis  (cats)—ingestion of 
contaminated water or feces.
• Morphologically, intestinal Cryptosporidium  
species very similar.
• Some species are host specific ( C. canis , C. 
felis); others ( C. parvum , C. muris ) infect 
multiple species.
• Immunosuppression—major risk factor; 
common causes feline leukemia virus, canine 
distemper virus, canine parvovirus, intestinal 
lymphoma.
• Immunocompetent animals—usually asympto ­
matic infection with fecal oocyst shedding.
  DIAGNOSIS
• Parasites—giardiasis, trichuriasis.
• Infectious agents—parvovirus, coronavirus, 
feline infectious peritonitis, Salmonella , 
Campylobacter , Rickettsia , Histoplasma .• Metabolic—hypoadrenocorticism, 
hyperthyroidism (cats).
• Infiltrative diseases—e.g., inflammatory 
bowel disease, intestinal lymphoma.
• Dietary indiscretion or intolerance.
• Toxicities—medications, lead, etc.
Usually normal, can reflect underlying disease.
• Sugar and zinc sulfate centrifugal flotation—
specific gravity = 1.18–1.3; concentrates fecal 
oocysts (oocysts are 5  μm, routine salt flotation 
often fails); oocysts best seen with modified 
acid­fast stain, may have slight pink color.
• Fecal antigen detection test (ProSpecT 
Cryptosporidium  Microtiter Assay, Color ­Vue 
Cryptosporidium ) available for humans.
• Fluorescent antibody assay—veterinary 
diagnostic laboratories.
• PCR—commercial laboratories; more 
sensitive for diagnosis than other techniques.
• Submitting feces to laboratory—laboratory ­
specific protocols; can mix 1 part 100% 
formalin with 9 parts feces to inactivate oocysts 
and decrease health risk to laboratory personnel.
• Gross lesions—enlarged mesenteric lymph 
nodes, hyperemic intestinal (especially ileal) 
mucosa; fix specimens in Bouin’s or formalin 
solution within hours of death; autolysis causes 
rapid loss of intestinal surface with organisms.
• Microscopic lesions—villous atrophy, 
reactive lymphoid tissue, inflammatory 
infiltrates in lamina propria; parasites 
throughout intestines, most numerous in 
distal small intestine.
  TREATMENT
• Outpatient.
• In immunocompetent animals—diarrhea 
usually mild and self ­limiting; withhold food 
for 24–48h to control diarrhea; oral glucose ­ 
electrolyte solution if mild diarrhea; 
parenteral fluids (isotonic with potassium 
added) if severe diarrhea.
• No drugs currently labeled for animal use 
• Paromomycin (Humatin®)—125–165 mg/
kg PO q12h for 5 days; aminoglycoside 
effective in humans with acute intestinal 
symptoms; may cause nephropathy in young 
animals with damaged gastrointestinal barrier; 
monitor urine for casts during therapy.• Tylosin—11 mg/kg PO q12h for 28 days; 
reported effective in cat with concurrent 
lymphocytic duodenitis.
• Nitazoxanide (Alinia®)—25 mg/kg PO 
q24h for 7–28 days; reduces oocyst shedding 
in cats; associated with vomiting (responsive 
to antiemetics); used in limited number of 
cats.
  FOLLOW-UP
• T reatment efficacy based on clinical 
• Monitor oocyst shedding in feces 2 weeks 
after treatment completion or if signs persist.
• Prognosis excellent if underlying disease 
treated.
Possible—transmission of infection from dogs 
and cats to humans possible; in general, 
transmission from pets to people rare.
Disinfection
• 10% formaldehyde solution or 5% 
ammonia solution will kill oocysts, but 
requires 18 hours of exposure; 50% ammonia 
solution kills oocysts in 30 minutes.
• Resistant to commercial bleach (5.25% 
sodium hypochlorite) and chlorination of 
drinking water.
• Moist heat (steam or pasteurization, 
>55 °C), freezing and thawing or thorough 
drying also effective.
Lucio ­Forster A, Griffiths JK, Cama VA, et al. 
Minimal zoonotic risk of cryptosporidiosis 
from pet dogs and cats. T rends Parasitol 
2010, 26:174–179.
Authors  Matt Brewer and Jeba R.J. Jesudoss 
Chelladurai
Consulting Editor  Amie KoenigCryptosporidiosis

348  Blackwell’s Five-Minute Veterinary Consult  
CCrystalluria
  BASICS
Appearance of crystals in urine. This finding 
may be normal, clinically significant or 
artifactual.
• Identification of crystals formed in vitro 
does not justify therapy.
• Crystals form only in urine that is, or recently 
has been, supersaturated with crystallogenic 
substances; thus in vivo crystalluria represents 
risk factor for urolithiasis.
• Certain crystal types such as cystine, urate, 
or 2,8-dihydroxyadenine may indicate 
underlying disease; proper identification and 
interpretation of urine crystals important in 
formulation of medical protocols to dissolve 
uroliths.
• Crystalluria in individuals with anatomi -
cally and functionally normal urinary 
tracts usually harmless because crystals 
eliminated before they grow large enough 
to interfere with normal urinary function; 
however, they represent a risk factor for 
urolithiasis.
• Crystals that form following elimination or 
removal of urine from the patient often are of 
little clinical importance; in recent studies 
following time and temperature changes, 
crystals formed in 28% of dog and cat 
samples that were initially free of crystals.
• Detection of some types of crystals (e.g., 
cystine and ammonium urate) in clinically 
asymptomatic patients or detection of any form 
of crystals in fresh urine collected from patients 
with confirmed urolithiasis may have diagnostic, 
prognostic, or therapeutic importance.
• Drug crystals detected in patients admin -
istered high doses of medications such as 
allopurinol, sulfadiazines, or fluoroquinolones 
should prompt therapy changes due to risk 
for formation of drug-containing uroliths.
Renal/urologic/hepatic.
• Calcium oxalate in miniature schnauzer, 
bichon frisé, Yorkshire terrier, Lhasa apso, 
miniature poodle dogs; Burmese, Himalayan, 
Persian cats.
• Cystine in dachshunds, English bulldogs, 
Newfoundlands, and others.
• Ammonium urate in Dalmatians and 
English bulldogs.
• Struvite in any dog with concomitant 
urinary tract infection (UTI).
• Struvite in cats not typically associated 
with UTIs.
• Xanthine in cavalier King Charles spaniels.
• 2,8-dihydroxyadenine in North American 
indigenous dogs and wolves.SIGNS
None, or those caused by concomitant 
CAUSES
In Vivo Variables
• Concentration of crystallogenic substances 
in urine (in turn influenced by rate of 
excretion and urine concentration).
• Urine pH (struvite and calcium phosphate 
most common in neutral-to-alkaline urine; 
ammonium urate, sodium urate, calcium 
oxalate, cystine, and xanthine crystals most 
common in acid-to-neutral urine).
• Solubility of crystallogenic substances in 
urine.
• Excretion of diagnostic agents (e.g., radio  - 
paque contrast agents) and medications (e.g., 
sulfonamides).
• Dietary influence—hospital diet may differ 
from home diet; timing of sample collection 
(fasting vs. postprandial) may influence 
evidence of crystalluria.
In Vitro Variables
• Temperature.
• Evaporation.
• pH changes following sample collection.
• Technique of specimen preparation—  
centrifugation versus noncentrifugation, 
volume of urine examined.
• Important in vitro changes that occur 
following urine collection may enhance 
formation or dissolution of crystals; when 
knowledge of in vivo urine crystal type and 
quantity especially important, examine fresh 
specimens, ideally at body temperature; if not 
possible, they should be at room temperature, 
not refrigeration temperature.
• Collection container—spurious crystals 
may be contaminants from unclean collection 
containers.
See preceding discussion.
  DIAGNOSIS
Ammonium Urate, Sodium Urate, 
and Amorphous Urate Crystalluria
• Uncommonly seen in apparently healthy 
• Frequently seen in dogs and occasionally in 
cats with portal vascular anomalies, with or 
without concomitant ammonium urate 
uroliths.
• Observed in some dogs and cats with urate 
uroliths caused by disorders other than portal 
vascular anomalies, such as canine breeds 
identified as carriers of hyperuricosuria gene.
Bilirubin Crystalluria
• Observed in highly concentrated urine 
from some healthy dogs.• Large numbers in serial samples raises 
suspicion of abnormality in bilirubin 
metabolism.
• Usually associated with underlying diseases 
in cats.
Calcium Oxalate Monohydrate 
and Calcium Oxalate Dihydrate 
Crystalluria
• May be observed in apparently healthy 
dogs and cats and in dogs and cats with 
uroliths primarily composed of calcium 
oxalate.
• Calcium oxalate monohydrate crystals most 
commonly associated with ethylene glycol 
toxicity, but calcium oxalate dihydrate may be 
observed, or ethylene glycol toxicity may 
occur without crystalluria.
Calcium Phosphate Crystalluria
• Large numbers of crystals presumed to be 
composed of calcium phosphate have been 
observed in apparently healthy dogs, dogs 
with persistently alkaline urine, dogs with 
calcium phosphate uroliths, and dogs with 
uroliths composed of mixture of calcium 
phosphate and calcium oxalate.
• Small numbers of calcium phosphate 
crystals may occur in association with 
infection-induced struvite crystalluria.
• May be observed in dogs and cats with 
primary hyperparathyroidism, and renal 
tubular acidosis.
Struvite Crystalluria
• Observed in many dogs and cats that are 
healthy and as an artifact.
• Observed in dogs and cats with urinary 
tract disease without uroliths.
• Observed in dogs and cats with infection-
induced struvite uroliths, sterile struvite 
uroliths, nonstruvite uroliths, and uroliths of 
mixed composition (e.g., nucleus composed 
of calcium oxalate and shell composed of 
struvite).
Cystine Crystalluria
Observed in dogs and cats with inborn 
errors of metabolism characterized by 
abnormal transport of cystine and other 
dibasic amino acids; this metabolism defect 
can also lead to dilated cardiomyopathy 
in cats.
Uric Acid Crystalluria
• Uncommon in dogs and cats.
• Importance as described for ammonium 
and amorphous urates.
Xanthine Crystalluria
• Suggests administration of excessive dosages 
of allopurinol in conjunction with consumption 
of relatively high amounts of dietary purine 
precursors.
• Primary xanthinuria has been observed in 
cavalier King Charles spaniels.
• Primary xanthinuria and xanthine uroliths 
occur in cats.

Canine and Feline, Seventh Edition  349
C
Miscellaneous Crystalluria
• Uric acid monohydrate crystals from 
melamine/cyanuric acid toxicosis.
• Cholesterol crystals—observed in humans 
with excessive tissue destruction, nephrotic 
syndrome, and chyluria; observed in 
apparently healthy dogs.
• Hippuric acid crystals—apparently rare in 
dogs and cats; importance unknown.
• Leucine crystals in dogs—importance not 
determined; may occur in association with 
cystinuria.
• Tyrosine crystals—occur in association 
with severe liver disease in humans; 
uncommonly observed in dogs and cats 
with liver disorders; sodium urate needle-
like appearance commonly misinterpreted 
as tyrosine needles.
• 2,8-dihydroxyadenine—a genetic disorder, 
the result of metabolic abnormality due to 
deficiency of enzyme adenine phosphoribosyl 
transferase (APRT).
Drug-Induced Crystalluria
• May be observed following administration 
of radiopaque contrast agents.
• May be observed following treatment with 
sulfadiazine, fluoroquinolones, xanthine 
oxidase inhibitors, and tetracycline.
Drugs That May Alter Laboratory 
Results
• Urinary acidifiers (e.g., d-, l-methionine 
and ammonium chloride).
• Urinary alkalinizers (e.g., sodium bicarbo-
nate and potassium citrate).
• Bilirubin crystals may be associated with 
bilirubinemia and other laboratory abnor-
malities of hepatic disorders.
• Most dogs and cats with calcium oxalate 
and calcium phosphate crystalluria are 
normocalcemic; some are hypercalcemic; 
calciuria may be used as a future index for 
calcium oxalate stone formation and treat  ment 
evaluation.
• Some dogs and cats with calcium oxalate 
crystalluria may be acidemic.
• Serially examine fresh specimens for 
knowledge of in vivo urine crystals.
• Definitive identification of crystal 
composition depends on one or more of 
optical crystallography, infrared spectroscopy, 
X-ray diffraction, and electron microprobe 
analysis.OTHER LABORATORY TESTS
• Struvite crystalluria is not synonymous with 
infection and may be the result of normal in 
vivo or in vitro factors; when accompanied by 
elevated pH, bacteriuria, or pyuria on cysto  - 
centesis, UTI should be considered; imaging 
must be performed to assess for stones.
• Dogs and cats with ammonium urate 
crystalluria and portosystemic shunts often 
have high serum bile acid levels and hyper  - 
ammonemia.
• Ammonium urate and amorphous urate 
crystals are insoluble in acetic acid; 
addition of 10% acetic acid to urine 
sediment containing these crystals often 
yields uric acid and sometimes sodium 
urate crystals.
• Dogs and cats with calcium oxalate 
monohydrate crystalluria secondary to 
ethylene glycol poisoning have detectable 
levels of ethylene glycol in serum and urine 
up to 48 hours after ingestion.
• Cystine crystals are insoluble in acetic acid 
while struvite crystals are soluble; a urine 
nitroprusside test is positive for cystine.
• Sulfonamide crystalluria may be associated 
with a positive lignin test.
IMAGING
• Crystalluria may be associated with 
radiographically or ultrasonographically 
detectable uroliths.
• Abdominal radiographs should include the 
entire urethra.
• 25% of radiopaque stones are not seen on 
ultrasound.
• Empirical therapy for struvite urolithiasis if 
stone identified on radiographs and concur-
rent UTI caused by urease-producing bacteria.
• Basket retrieval, voiding urohydropropul-
sion, or aspiration through a transurethral 
catheter to retrieve small urocystoliths.
  TREATMENT
• Manage clinically important in vivo 
crystalluria by managing underlying cause(s) 
or associated risk factors.
• Minimize clinically important crystalluria 
by increasing urine volume, encouraging 
complete and frequent voiding, modifying 
diet, appropriate drug therapy, neutering where appropriate, and in some instances 
modifying pH.
See comments on urate crystalluria and 
  FOLLOW-UP
• Recheck urinalysis to determine if 
crystalluria is persistent.
• Re-radiograph or ultrasound, depending on 
crystal type, to determine if crystalluria has 
clinical significance or not.
• See specific urolith types for monitoring 
• Persistent crystalluria may contribute to 
formation of uroliths.
• Crystalluria may solidify crystalline-matrix 
plugs as in male pugs and cats, resulting in 
SEE ALSO
• Urolithiasis, Calcium Oxalate.
• Urolithiasis, Calcium Phosphate.
• Urolithiasis, Pseudo (Dried Blood, Ossified 
Material).
• Urolithiasis, Struvite—Cats.
• Urolithiasis, Struvite—Dogs.
• Urolithiasis, Urate.
• Urolithiasis, Xanthine.
• APRT = adenine phosphoribosyl 
transferase.
• UTI= urinary tract infection.
Author  Ewan D.S. Wolff
of Carl A. Osborne and Lisa K. Ulrich.(continued)  Crystalluria

350  Blackwell’s Five-Minute Veterinary Consult  
CCutaneous Drug Eruptions
  BASICS
OVERVIEW
• A wide spectrum of diseases and clinical 
signs that vary markedly in clinical 
appearance.
• Mild eruptions may go unnoticed or 
unreported; incidence rates for specific drugs 
are unknown.
• May have a familial basis (e.g., rabies 
vaccine reactions in canine littermates).
SIGNS
• Pruritus.
• Macular and papular rashes—commonly 
accompany pruritus as nonspecific sign of 
• Exfoliative erythroderma—diffuse 
erythematous response caused by vasodila-
tion; often leads to exfoliation (diffuse 
scaling).
• Urticaria/angioedema—immediate (type I) 
hypersensitivity; requires prior sensitization; 
increased vascular permeability leads to fluid 
leakage.
• Hypersensitivity vasculitis—type III 
response; inflammation of cutaneous 
vasculature; results in poor blood flow and 
anoxic injury to recipient tissue.
• Eosinophilic dermatitis with edema 
(Wells-like syndrome) of dogs—deeply 
erythematous plaques or macules (may be 
targetoid) accompanied by marked edema; 
localized, regional, or generalized distribu-
tion; clinical appearance of lesions may be 
indistinguishable from vasculitis and 
erythema multiforme (EM).
• EM—erythematous macules or plaques 
expand peripherally and may clear in 
center (targetoid); multiple shapes/forms 
noted.
• Stevens-Johnson syndrome (SJS)—similar 
to toxic epidermal necrolysis (TEN) with less 
extensive epidermal detachment (<30%) and 
often involvement of oral mucosa.
• TEN—extensive ( >30%) necrosis and 
sloughing of epidermis in sheets; results 
in moist and intensely inflamed skin 
surface.
• Drug-induced pemphigus/pemphigoid—
least common drug reaction in animals; can 
closely mimic autoimmune (spontaneous) 
disease; symptoms may persist after drug 
withdrawal.
• Any drug.
• Can occur after first dose or after weeks to 
months of administration.
• Exfoliative erythroderma—most often 
associated with shampoos and dips; also reaction to topical ear medications (in ear 
canals and on concave pinnae).
• Eosinophilic dermatitis with edema—
strong association with concurrent acute 
gastrointestinal disease.
• Pemphigus foliaceus—may be triggered by 
specific topical flea and tick control products; 
lesions may include “splash zone” where 
product was applied.
  DIAGNOSIS
• Pruritus, macular/papular rashes, and 
urticaria/angioedema—allergic and parasitic 
diseases (atopic diseases, contact hypersensi-
tivity, flea-bite hypersensitivity, scabies, 
stinging insects).
• Exfoliative erythroderma—epitheliotropic 
lymphoma in old dogs and cats.
• Vasculitis—infectious, neoplastic, autoim-
mune disease and idiopathic.
• EM/SJS/TEN—respiratory infections, 
herpes virus, parvovirus, bacterial infection 
(noncutaneous), and internal neoplasia; 
idiopathic/chronic form of EM occurs in 
older adult dogs.
• Pemphigus/pemphigoid—consider drug 
reaction whenever these diseases diagnosed; 
however, spontaneously occurring disease 
more common.
Potential for concurrent hepatic, renal, 
and gastrointestinal disease with cases of 
vasculitis.
• Dogs with vasculitis—rickettsial serology.
• Cats with vasculitis—feline immunodefi-
ciency virus (FIV) and feline leukemia virus 
(FeLV) serology, rule out feline infectious 
• Bacterial and fungal cultures with vasculitis 
or pyogranulomatous inflammation.
Skin biopsy—mandatory for diagnosis of 
most drug-induced diseases.
Determined by specific disease process.
  TREATMENT
• Discontinue use of offending or suspect 
drug.
• SJS/TEN—intensive supportive care and 
fluid/nutritional support because of fluid and 
protein exudation and risk of sepsis.
• Pain relief when indicated—minimal drug 
use recommended when drug eruption 
suspected.  MEDICATIONS
Most conditions respond to immunosuppres-
sive therapy if withdrawal of offending drug 
alone is insufficient (controversial in case of 
SJS/TEN).
Avoid offending drug or any other drug in 
same class or family.
  FOLLOW-UP
Inpatient—if debilitated.
• Secondary infection.
• Electrolyte and plasma protein depletion 
(SJS/TEN).
• Some reactions appear to activate self-
perpetuating immune responses.
• Some drug metabolites may persist for 
days to weeks and provoke continued 
response.
• TEN—prognosis poor.
• Vasculitis—prognosis guarded when 
systemic complications.
• EM = erythema multiforme.
• SJS = Stevens-Johnson syndrome.
• TEN = toxic epidermal necrolysis.
2018.
Author  Daniel O. Morris
Resnick

Canine and Feline, Seventh Edition  351
CCuterebriasis
  BASICS
OVERVIEW
• Flies of the genus Cuterebra  are found in 
the Americas, where they are obligatory 
parasites of rodents and lagomorphs. Adult 
flies lay eggs on blades of grass or in nests; 
they hatch and crawl onto the skin of 
passing host. The small maggots enter a 
body orifice, migrate through various 
internal tissues, and ultimately over several 
weeks to months make their way to the skin, 
where they establish a warble. The mature 
maggots, which may be an inch long, then 
drop out of the rodent or rabbit host and 
pupate in the soil.
• Dogs and cats become infected when they 
contact a blade of grass upon which an egg 
containing an infective maggot is stimulated 
to hatch and attach onto the passing animal. 
The maggots then crawl around on the cat or 
dog until they find an orifice in which to 
enter.
• Dogs and cats can develop maggots in 
warbles or can develop signs associated with 
larvae migrating within their tissues.
• Dogs and cats can present with respiratory 
signs, neurologic signs, ophthalmic lesions, or 
maggots in their skin.
• Dogs and cats—all ages.
• In northern United States, most cases occur 
in late summer and early autumn, based on 
time of emergence of adult egg-laying females 
in spring and early summer.
SIGNS
• Dermatologic—warble containing bot with 
protruding spiracles.
• Neurologic—ataxia, circling, paralysis, 
blindness, recumbency.
• Ophthalmic lesions—larva in conjunctiva.
• Respiratory—eosinophilic respiratory 
disease.
• Dogs and cats with access to outdoors, 
where they contact eggs and larvae.
• Neonatal cats have been infected, presum-
ably with larvae carried on queen’s fur.
  DIAGNOSIS
• Respiratory—allergies, lungworms, 
migrating ascarids or hookworms.
• Neurologic—rabies, distemper, angio  - 
strongylosis.
• Ophthalmic lesions—larval Hypoderma  or 
Oestrus .• Dermatologic—mature warble unmistak-
able, young warble may present as pustule or 
papule.
Eosinophilia may be present, otherwise no 
specific findings.
N/A
IMAGING
CT, MRI—may show intracranial lesions in 
cats.
N/A
  TREATMENT
• Can remove maggots from subcutaneous 
lesions, eyes, or nares (see Web Video 1).
• Manifestations of lung migration may be 
alleviated by corticosteroids.
• Neurologic disease has poor prognosis.
• Ivermectin 0.2 mg/kg SC should kill 
migrating maggots; can be administered either 
to alleviate signs caused by maggots suspected 
of migrating in lungs, or to kill larvae in other 
tissues, including CNS; pretreatment with 
corticosteroids may mitigate inflammatory 
reaction to dying worms.
• Products containing isoxazolines (i.e., 
afoxolaner, fluralaner, lotilaner, andsarolaner), 
when routinely given to cats and and dogs, 
may prevent migration and warble formation 
by Cuterebra  spp. Efficacy and potential side 
effects in patients with migrating maggots has 
not been reported.
  FOLLOW-UP
Good return of function following ivermectin 
treatment is possible.
• In northern United States disease is 
seasonal, with most cases occurring in late 
summer and early fall when adult flies are 
active; seasonality is less demarcated in areas 
where warmer temperatures and active flies 
occur through longer periods of the year.
• Does not appear to result in prolonged 
immunity; the same animal can develop skin 
lesions several years in a row.• Application of monthly heartworm 
preventatives (avermectin-containing 
products), flea development control products 
(lufenuron-containing products), or topical 
flea and tick treatments may either prevent 
the maggots from developing, or may kill 
them before they access an orifice for entry. 
However, based on anecdotal information, 
some cats and dogs on these products still 
develop warbles with maggots.
The maggots in the dog or cat pose no 
Bordelon JT, Newcomb BT, Rochat MC. 
Surgical removal of a Cuterebra  larva from 
the cervical trachea of a cat. J Am Anim 
Hosp Assoc 2009, 45:52–54.
Edelmann ML, Lucio-Forster A, Kern TJ, et al. 
Ophthalmomyiasis interna anterior in a dog: 
keratotomy and extraction of a Cuterebra sp. 
larva. Vet Ophthalmol 2014, 17:448–453.
Thawley VJ, Suran, JN, Boller EM. 2013 
Presumptive central nervous system 
cuterebriasis and concurrent protein-losing 
nephropathy in a dog. J Vet Emerg Crit 
Care 2013, 23:335–339.

352  Blackwell’s Five-Minute Veterinary Consult  
CCyanosis
  BASICS
A bluish discoloration of the skin and mucous 
membranes owing to an increase in the 
amount of reduced, or deoxygenated, 
hemoglobin within the blood.
• Concentration of deoxygenated 
hemoglobin—must be >5 g/dL to detect 
condition; thus anemia may obscure recognition 
of cyanosis. • Central—associated with systemic 
arterial hypoxemia or hemoglobin abnormalities. 
• Peripheral—limited to one or more extremities 
of the body; associated with diminished 
peripheral blood flow; arterial oxygen tension 
and saturation typically normal.
Arterial Hypoxemia
• Low partial pressure of inspired oxygen 
(e.g., high altitude). • Hypoventilation due to 
primary neurologic disorders affecting brain, 
cervical spinal cord, or lower motor neuron; 
centrally acting respiratory depressant drugs; 
chest wall injuries; pleural space diseases; 
upper airway obstructions. • Ventilation–
perfusion mismatching resulting in impaired 
gas exchange (e.g., pulmonary parenchymal or 
thromboembolic diseases). • Diffusion 
impairment fromthickening of alveolar barrier 
through which oxygen must pass to reach red 
blood cells (RBCs); interstitial lung disease 
may cause this. • Addition of deoxygenated 
venous blood to arterial circulation—
congenital right-to-left shunting cardiac 
defects (e.g., tetralogy of Fallot, transposition 
of great vessels); reversed shunting cardiac 
defects caused by high pulmonary vascular 
resistance (e.g., right-to-left shunting patent 
ductus arteriosus [PDA], atrial septal defect 
[ASD], ventricular septal defect [VSD]).
Abnormal Hemoglobin
• Methemoglobin—most common abnormal 
heme pigment; unable to bind oxygen; 
normally formed at low rate in erythrocytes; 
cats with significant exposure to acetaminophen 
will appear cyanotic. • Nicotinamide adenine 
dinucleotide dependent methemoglobin 
reductase (NADH-MR)—intracellular 
reductive enzyme; maintains methemoglobin : 
hemoglobin ratio at <2%; deficiency and/or 
exposure to oxidizing agents causes methemo -
globinemia. • Hypoxia—when >20–40% of 
hemoglobin has been oxidized to 
methemoglobin.
Other
• Peripheral cyanosis—results from increased 
oxygen extraction from arterial supply to an 
area (e.g., a limb); caused by severe 
vasoconstriction, poor peripheral blood flow, 
obstruction to flow associated with arterial 
thromboembolism, or stagnation or 
obstruction of venous blood flow; difficult to see, with exception of discolored paw pads in 
cats with arterial thromboembolism. 
• Differential cyanosis—with reverse shunting 
PDA, head and neck receive oxygenated blood 
via brachiocephalic trunk and left subclavian 
artery, which arise from aortic arch; rest of the 
body receives desaturated blood through 
ductus located in descending aorta.
• Central—all systems affected. 
• Peripheral—may diminish or abolish 
neuromuscular function of affected limb(s).
• Right-to-left cardiac shunts in association with 
high pulmonary vascular resistance and 
pulmonary hypertension (Eisenmenger 
physiology)—dogs: Keeshond, English bulldog, 
klee kai, and beagle; some cats; generally young 
animals. • T racheal collapse—usually young or 
middle-aged small-breed dogs (e.g., Pomeranian, 
Yorkshire terrier, poodles). • Acquired laryngeal 
paralysis—most common in old large-breed 
dogs (e.g., retrievers). • Hypoplastic trachea—
identified in young English bulldogs; 
occasionally other breeds. • Brachycephalic 
airway syndrome—dogs: English and French 
bulldogs, Pekinese, pugs, Boston terrier, and 
other brachycephalic breeds. • Asthma—cats: 
higher incidence reported in Siamese.
SIGNS
• Central—stridor; respiratory distress; 
cough; voice change; episodic weakness; 
syncope; exposure to oxidizing substances or 
drugs causing methemoglobinemia. 
• Peripheral—limb paresis or paralysis.
• Heart murmur or splitting of second heart 
sound—with cardiac disease or pulmonary 
hypertension. • Pulmonary crackles or 
wheezes—with pulmonary edema or 
respiratory disease. • Muffled heart sounds—
owing to pleural space or pericardial disease. 
• Upper airway stridor with laryngeal paralysis. 
• Honking cough—typical of tracheal 
collapse; often induced by tracheal palpation. 
• Dyspnea—may be inspiratory, expiratory, or 
a combination (see Differential Diagnosis). 
• Limbs—may be cyanotic, cool, pale, painful, 
and edematous; can lack a pulse in conditions 
causing peripheral cyanosis. • Weakness—can 
be generalized and persistent with severe 
cardiac diseases; can be episodic and especially 
noticeable with exercise or excitement. 
• Posterior paresis or paralysis—can be seen 
with distal aorta arterial thromboembolism; 
differentiated from primary neuromuscular 
disease by absence (or near absence) of pulses.
CAUSES
Respiratory System
• Larynx—paralysis (acquired or congenital); 
collapse; spasm; edema; trauma; neoplasia; 
granulomatous disease. • T rachea—collapse; neoplasia; foreign body; trauma; hypoplasia. 
• Lower airway and parenchyma—pneumonia 
(viral, bacterial, fungal, eosinophilic, myco  - 
bacteria, aspiration); chronic bronchitis; 
hypersensitivity bronchial disease or asthma; 
bronchiectasis; neoplasia; foreign body; 
parasites ( Filaroides , Paragonimus, Pneumocystis 
jiroveci , toxoplasmosis, Aelurostrongylus  spp.); 
pulmonary contusion or hemorrhage; 
noncardiogenic edema (smoke inhalation, 
snake bite, electric shock); near drowning. 
• Pleural space—pneumothorax; infectious 
(bacterial, fungal, feline infectious peritonitis 
[FIP]); chylothorax; hemothorax; pyothorax; 
neoplasia; trauma. • Thoracic wall or 
diaphragm—congenital (pericardial, 
diaphragmatic hernia); trauma (diaphragmatic 
hernia, fractured ribs, flail chest); neuromuscular 
disease (tick bite paralysis, coonhound 
paralysis).
Cardiovascular System
• Congenital defects—Eisenmenger 
physiology (right-to-left shunting PDA, VSD, 
ASD); tetralogy of Fallot; truncus arteriosus; 
double outlet right ventricle; anomalous 
pulmonary venous return; atresia of aortic or 
tricuspid or pulmonary valves. • Acquired 
disease—mitral valve disease; cardiomyopathy. 
• Pericardial effusion—idiopathic disease; 
neoplasia. • Pulmonary thromboembolic 
disease—hyperadrenocorticism; immune-
mediated hemolytic anemia; protein-losing 
nephropathy; dirofilariasis; severe, acute 
pancreatitis. • Pulmonary hypertension—
idiopathic; right-to-left cardiac shunts. 
• Peripheral vascular disease—arterial 
thromboembolism (feline cardiomyopathies); 
venous obstruction; reduced cardiac output; 
shock, arteriolar constriction.
Neuromusculoskeletal System
• Brainstem dysfunction—encephalitis; 
trauma; hemorrhage; neoplasia; drug-induced 
depression of respiratory center (morphine, 
barbiturates). • Cervical spinal cord 
dysfunction—edema; trauma; vertebral 
fractures; disk prolapse. • Neuromuscular 
dysfunction—overdose of paralytic agents 
(succinylcholine, pancuronium); tick bite 
paralysis; botulism; tetanus; acute polyradiculo  - 
neuritis (coonhound paralysis); 
dysautonomia; myasthenia gravis.
Methemoglobinemia
• Congenital—NADH-MR deficiency (dogs). 
• Ingestion of oxidant chemicals—acetami-
nophen; nitrates; nitrites; phenacetin; sulfona -
mides; benzocaine; aniline dyes; dapsone.
  DIAGNOSIS

  DIAGNOSIS
• Generalized—systemic hypoxemia or heme 
abnormality. • Peripheral only—reduced

Canine and Feline, Seventh Edition  353
C
blood flow to extremities. • Caudal body—  
right-to-left shunting PDA. • Cardiac versus 
respiratory causes—differentiation can be 
difficult; cardiac murmur may suggest 
cardiac disease, but murmurs are often heard 
in older patients with primary respiratory 
disease; higher hematocrit may make 
murmurs harder to hear; thoracic radiography 
and echocardiography useful for differentiation. 
• Central or peripheral neurologic signs—
should prompt concern for arterial hypoxemia 
owing to primary neuromuscular disease.
Breathing Pattern
• May help define cause. • Inspiratory 
effort—often associated with obstructive 
upper airway or pleural space disease; 
stridor frequently localizes problem to 
larynx or cervical trachea. • Expiratory 
effort—generally seen with obstructive 
lower airway disease. • Rapid shallow 
(restrictive)—may be associated with 
pleural space disease or neuromuscular 
abnormalities of thoracic wall.
• Color of blood—may be darkened; 
chocolate brown with methemoglobinemia. 
• Polycythemia—often accompanies 
congenital heart disease; may occur with 
chronic hypoxemia owing to severe respiratory 
disease. • Proteinuria—accompanies protein-  
losing nephropathies, which may result in 
secondary pulmonary thromboembolism. 
• Panhypoproteinemia—accompanies 
protein-losing enteropathies, which may lead 
to pulmonary thromboembolism.
• Co-oximetry to estimate percent of 
methemoglobin or carboxyhemoglobin. 
• Arterial blood gas analysis. • Urine 
protein : creatinine ratio—with suspected 
pulmonary thromboembolism secondary to 
protein-losing nephropathy.
IMAGING
• Radiography—essential for determining 
cause. • Echocardiography—aids in 
diagnosis of congenital or acquired cardiac 
disease, pulmonary hypertension, and 
pulmonary thromboembolism. • CT/
angiography—can further define obstructive 
nasal, pulmonary, or pleural space disease; 
gold standard for diagnosing pulmonary 
embolism in humans.
• Pulse oximetry to estimate oxygen saturation; 
inaccurate when carboxyhemoglobin or 
methemoglobin present. • Laryngoscopic 
examination—evaluate laryngeal structure and 
arytenoid function. • Bronchoscopy—often 
useful in diagnosis of airway and pulmonary 
diseases. • T ranstracheal wash, bronchoalveolar 
lavage, or fine-needle lung aspirate—often required to characterize bronchopulmonary 
diseases. • Thoracocentesis—required for 
diagnosis and treatment of pleural space 
disorders. • Electrocardiography—may reveal 
heart enlargement changes; unreliable; 
echocardiography better. • Lung biopsy—can be 
necessary for diagnosis of interstitial lung disease.
  TREATMENT
• Inpatient—immediate diagnostic testing 
and treatment. • Stabilization therapy (e.g., 
oxygen, thoracocentesis, tracheostomy)—
usually instituted before aggressive diagnostics. 
• Specific therapy—depends on ultimate 
diagnosis; usually exercise restriction and 
dietary modification required. • Surgical 
treatment—depends on primary disease 
process and extent of cardiac or respiratory 
involvement. • Warn the client when 
admitting the patient that diseases associated 
with cyanosis can have dire outcomes.
• Oxygen therapy—provide as soon as 
possible. • Additional drug therapy depends 
on final diagnosis. • Furosemide—aggressive 
use indicated with suspected cardiogenic 
pulmonary edema. • Methemoglobinemia as 
result of ingestion of oxidizing substances 
(acetaminophen)—give acetylcysteine as soon 
as possible (140 mg/kg PO/IV; then 70 mg/
kg q4h for five treatments); cimetidine 
(10 mg/kg PO; then 5 mg/kg PO q6h for 
48h) is useful adjunct to acetylcysteine; 
ascorbic acid (30 mg/kg PO q6h for seven 
treatments) may be of some value, but do not 
use as sole agent; methylene blue given IV 
followed by oral supplementation reported as 
successful treatment modality in dogs. 
• Sildenafil citrate—phosphodiesterase type 5 
inhibitor used to treat pulmonary arterial 
hypertension at 1–3 mg/kg PO q8–12h.
Avoid using paralytic agents (succinylcholine, 
pancuronium) and agents that cause 
profound depression of respiratory center 
(morphine, barbiturates).
  FOLLOW-UP
• Patients in an oxygen cage should be 
disturbed as infrequently as possible for 
monitoring. • Assess efficacy of therapy—changes in depth and rate of respiration; color 
of mucous membranes (should return to 
normal pink color if cause is not anatomic 
shunt and patient has adequate reserves); 
pulse oximetry or arterial blood analysis. 
• Instruct client to monitor mucous 
membrane color and respiratory effort, and 
advise immediate veterinary care if cyanotic 
condition returns.
Advanced pulmonary or airway disease and 
severe cardiac disease—poor long-term 
• Obesity—can complicate or exacerbate 
underlying respiratory or cardiac diseases. 
• Ascites—can complicate or exacerbate 
respiratory effort and reduce lung capacity 
due to cranial displacement of diaphragm.
Congenital cardiac abnormalities—usually 
the cause in young patients.
• Advanced pregnancy may exacerbate signs 
because of pressure on diaphragm and 
reduced lung expansion. • Fetuses likely to be 
harmed or aborted by hypoxemia associated 
with cyanosis.
SEE ALSO
• Dyspnea and Respiratory Distress.
• Panting and Tachypnea.
• Stertor and Stridor.
• FIP = feline infectious peritonitis. 
• NADH-MR = nicotinamide adenine 
reductase.
• PDA = patent ductus arteriosus.
• VSD = ventricular septal defect.
Author  Sean B. Majoy
Ned F . Kuehn.
available online(continued)  Cyanosis

354  Blackwell’s Five-Minute Veterinary Consult  
CCyclic Hematopoiesis
  BASICS
OVERVIEW
• Cyclic hematopoiesis in color-dilute gray 
collie pups, also known as gray collie 
syndrome, is characterized by frequent 
episodes of infection with failure to thrive 
and early death. Systems affected are hemato  - 
poietic, ocular, respiratory, gastrointestinal, 
and skin. Pups may appear normal for the 
first 4–6 weeks and then develop diarrhea, 
conjunctivitis, gingivitis, pneumonia, skin 
infections, joint pain, and fever.
• Episodes of illness, varying from inactivity 
accompanied by fever to life-threatening 
infection, repeat at 11–14-day intervals.
• Affected pups are usually smaller than their 
littermates at birth, weak, and often pushed 
aside by their mothers.
• Cyclic hematopoiesis in the collie breed is 
present only in the color-dilute pups. The 
color dilution and bone marrow disorder are 
inherited as an autosomal recessive trait. This 
condition has also been reported in crossbred 
collie/beagle pups.
• Clinical signs occur as early as 1–2 weeks of age 
and are always apparent by 4–6 weeks of age. 
Affected dogs rarely live beyond 2–3 years of age.
• An apparently similar disease was reported 
in normal-colored pups in two border collie 
litters in the UK. Cyclic hematopoiesis has 
also been reported in Pomeranians, Cocker 
Spaniels, and a Basset Hound, but the disease 
is not well characterized in these breeds.
• Cyclic hematopoiesis has been observed in 
two cats with feline leukemia virus (FeLV) 
SIGNS
• Failure to thrive.
• Conjunctivitis.
• Gingivitis.
• Pneumonia.
• Skin infections.
• Joint pain.
• Dilute coat color with color dilution of 
nasal epithelium.
• Smaller and weaker than normal-colored 
• Fever.
• Watery eyes, reddened gums, tonsillitis, and 
diarrhea nearly always present during phase of 
hematopoietic cycle when clinical signs are 
evident; other signs vary depending on 
presence of infection in various body systems.• Signs and symptoms of FeLV in cats.
• Inherited disease in purebred or crossbred 
collie dogs.
• FeLV infection in cats.
  DIAGNOSIS
• Coat color dilution and nasal epithelial 
color dilution are always present in collies or 
collie mixed breeds with cyclic hematopoiesis.
• Coat color dilution as a result of dilute gene 
expression is also observed in collies. These 
dogs have blue or lilac coat color with normal 
color intensity on nose and do not develop 
cyclic hematopoiesis.
• T rapped neutrophil syndrome is another 
autosomal recessive inherited neutropenia in 
border collie pups who present with recurrent 
infections and musculoskeletal disease, 
usually between 6 and 12 weeks of age. 
Unlike cyclic neutropenia, affected pups have 
persistent neutropenia. A DNA test for this 
disease is available.
• Cats will present with signs and symptoms 
consistent with FeLV infection.
• CBC—severe neutropenia, lasting 2–5 days, 
followed by neutrophilia, and occurring at 
11–14-day intervals with mild normocytic to 
microcytic anemia in dogs; slight to moderate 
normocytic or macrocytic anemia in cats.
• Local swelling, redness, and systemic signs of 
infection usually occur during first days of 
neutrophilic phase of disease cycle; therefore, on 
initial CBC examination, neutrophilia with 
moderate monocytosis is usually observed.
A DNA mutation test is available for canine 
cyclic hematopoiesis from Animal Genetics.
  TREATMENT
• Recombinant G-CSF or lentivirus-medi-
ated G-CSF can be administered to shorten 
period of neutropenia and reduce infections.
• Antibiotics and supportive therapy to treat 
or relieve symptoms.
• Bone marrow transplantation eliminates 
cyclic hematopoiesis and can be curative.
Antibiotics and intravenous fluids as 
indicated for infections.  FOLLOW-UP
Owner advised to watch for signs of 
Dogs should not be boarded with other 
animals.
Infections can be life threatening if 
untreated.
Intermittent infections are expected. 
Prognosis is guarded.
Carriers or affected collies should not be 
bred.
SEE ALSO
• Neutropenia.
• G-CSF = granulocyte colony-stimulating 
factor.
Diagnostic Guide and Color Atlas. St. 
Louis, MO: Elsevier Health Sciences, 
2012, p.148.
Author  June C. Huang
editors acknowledge the prior contribution of

Canine and Feline, Seventh Edition  355
CCylindruria
  BASICS
OVERVIEW
• Increased number of casts in urine 
sediment.  • Occasional hyaline and granular 
casts can be found in clinically normal 
animals.  • High numbers of casts indicate 
tubular pathology, but do not correlate with 
degree of damage.  • Can develop with 
primary renal disease or systemic disorders 
that secondarily affect kidneys. •  Absence of 
casts does not exclude possibility of renal 
tubular disease. •  Systems affected—renal/
urologic.
Nephrotoxicosis
• Toxins—ethylene glycol, grape/raisin 
ingestion (dogs), lily ingestion (cats), 
hypercalcemia. •  Nephrotoxic drugs—e.g., 
aminoglycosides, amphotericin B, cisplatin, 
nonsteroidal anti-inflammatory drugs, 
angiotensin-converting enzyme inhibitors, 
radiocontrast agents.
Renal Ischemia
• Dehydration. • Low cardiac output. • Renal 
vessel thrombosis. • Hemoglobinuria. 
• Myoglobulinuria.
Renal Inflammation
Infectious diseases (e.g., pyelonephritis, 
leptospirosis, feline infectious peritonitis, 
tick/vector-borne disease).
Glomerular Disease
• Glomerulonephritis. •  Amyloidosis.
  DIAGNOSIS
• Cylindruria with azotemia and adequately 
concentrated urine (specific gravity >1.030 in 
dogs and >1.040 in cats)—consider prerenal 
disorders such as dehydration. •  Cylindruria 
with azotemia and inadequately concentrated 
urine—consider renal failure. •  Cylindruria 
with leukocytosis—consider pyelonephritis or 
other infectious and inflammatory disorders. 
• Cylindruria with glucosuria and proteinuria— 
consider renal tubular necrosis. •  T ransient 
hyaline and/or granular casts can be seen after 
strenuous exercise.
• Casts classified by appearance and 
quantified per low power field. •  Granular 
casts (fine or coarse) associated with tubular 
degeneration, inflammation, or necrosis. 
• Hyaline casts can be seen with proteinuria, dehydration, and after diuresis. •  Waxy casts 
usually seen with chronic kidney disease. 
• Epithelial casts formed from degeneration 
of renal tubular epithelial cells; most 
commonly seen with acute tubular injury. 
• White blood cell (WBC) casts indicate 
renal inflammation (e.g., pyelonephritis). 
• Red blood cell (RBC) casts indicate renal 
hemorrhage. •  Fatty casts suggest renal 
tubular injury. •  Chemistry profile may show 
azotemia and hyperphosphatemia. •  CBC 
may show anemia, erythrocytosis, leukocyto-
sis, and/or thrombocytopenia depending on 
underlying pathology.
• Determine urine protein : creatinine ratio 
to evaluate magnitude of proteinuria. 
• Perform urine culture to rule out urinary 
tract infection in patients with pyuria or 
WBC casts. Also consider ultrasound ± 
radiography to assess for pyelonephritis, 
nephroliths, etc. •  Test for systemic infections 
as indicated. •  If thrombocytopenic or RBC 
casts are present, perform coagulation studies 
to rule out consumptive coagulopathy such as 
disseminated intravascular coagulation.
Results
• Delayed processing of urinalysis and 
examination of urine sediment may result 
in disappearance of casts; ideally should be 
examined within 30 minutes of collection. 
• Alkaline urine can cause dissolution of 
casts. •  Low speed centrifugation necessary to 
prevent cast destruction.
Yes
Consider renal biopsy if kidney disease 
persists or progresses and cause cannot be 
determined from routine diagnostic tests.
  TREATMENT
• Manage as outpatient unless patient is 
dehydrated or has decompensated kidney failure. 
• Acute kidney injury and chronic kidney 
disease should be managed according to 
standard recommendations. •  If patient 
cannot maintain hydration, administer 
parenteral fluid therapy. •  Consider dialysis if 
toxin exposure or leptospirosis infection.
Avoid nephrotoxic drugs.  FOLLOW-UP
• Physical examination including patient’s 
weight to assess hydration status. •  Blood 
pressure monitoring. •  CBC/chemistry/
urinalysis monitoring.
Avoid or correct risk factors (e.g., exposure 
to toxins, infectious disease prevention, 
etc.).
Irreversible renal disease, depending on 
underlying cause of cylindruria.
Possible in patients with leptospirosis. Use 
safety precautions when handing urine.
SEE ALSO
Nephrotoxicity, Drug-Induced.
Latimer K. Duncan and Prasse’s Veterinary 
Laboratory Medicine Clinical Pathology, 
5th ed. Ames, IA: Wiley-Blackwell, 2011, 
pp. 264–272.
Sink C, Weinstein N. Practical Veterinary 
Urinalysis. Ames, IA: Wiley-Blackwell, 
2012, pp. 69–84.
Stockham S, Scott M. Fundamentals of 
Ames, IA: Wiley-Blackwell, 2008, pp. 
472–473.
Author  T racie D. Romsland
of Allyson C. Berent and Cathy E. 
Langston.

356  Blackwell’s Five-Minute Veterinary Consult  
CCytauxzoonosis
  BASICS
OVERVIEW
• Infection with the protozoan Cytauxzoon 
felis.
• Affects vascular system of lungs, liver, 
spleen, kidneys, and brain; bone marrow and 
developmental stages of red blood cells 
(RBCs) affected as well.
• Uncommon in most regions, but common 
during the spring and summer in endemic 
regions.
• Affects feral and domestic cats in south-
central, southeastern, and mid-Atlantic 
United States; range appears to be expanding 
towards eastern and northeastern United 
States.
• Related Cytauxzoon  spp. have been identified 
in Europe and Asia, but have not been 
associated with classic Cytauxzoonosis (see 
Signs) as seen in North America.
• Domestic cats of all ages.
• Wild felids are also at risk.
• No breed or sex predilection, although 
most cases are diagnosed in young cats that 
have access to outdoors.
SIGNS
• Most cats have severe illness at presentation.
• Pale mucous membranes.
• High fever.
• Icterus.
• Splenomegaly.
• Some cats may be infected but 
• Bite of infected tick (primarily Amblyomma 
americanum  or Dermacentor variabilis ).
• Roaming in areas shared by reservoir hosts 
(bobcats).
• Living in same household/region as cat 
diagnosed with cytauxzoonosis.
  DIAGNOSIS
• Other causes of pancytopenia such as sepsis 
and panleukopenia.
• Other causes of fever and jaundice such as 
pancreatitis, hepatitis, and cholangitis.
• Bicytopenia or pancytopenia are the most 
common findings; thrombocytopenia is 
almost always present.• Moderate hyperbilirubinemia and 
bilirubinuria.
• Mild hyperglycemia.
• If present, anemia is believed to be 
secondary to hemolysis.
• Fresh blood smear— Cytauxzoon  erythro-
cytic form; 1–3  μm in diameter; shape of 
signet ring or safety pin.
• Schizont-infected monocyte/macrophages 
may be observed on feathered edge of thin 
blood smears.
• Splenic, lymph node, liver, or bone marrow 
aspirate—best suited to demonstrate extra- 
erythrocytic schizont forms.
• PCR assay is commercially available.
• Blood type in all cats prior to transfusion.
IMAGING
Radiographs or ultrasound may assist in 
identifying pleural effusion or pulmonary 
edema.
N/A
Organisms inside myeloid cells in bone 
marrow aspirate and in dramatically enlarged 
myeloid cells in vessels of multiple organs 
including lung, liver, spleen, kidney, and 
brain.
  TREATMENT
• Inpatient with aggressive supportive therapy 
including supplemental oxygen.
• Blood transfusion.
• Feeding tube for medication and nutri-
tional support.
• Combination of atovaquone (15 mg/kg PO 
q8h with a fatty meal) and  azithromycin 
(10 mg/kg PO q24h) and supportive care is 
associated with survival rates of 60%.
• Imidocarb dipropionate—5 mg IM two 
injections 14 days apart has been recom-
mended, but is associated with survival rates 
of approximately 27%.
• Heparin (100–300 U/kg SC q8h or 
300–900 U/kg/day as IV CRI) until time of 
discharge (longer if significant thrombosis 
such as pulmonary thromoboembolism is 
present).
• With aggressive supportive care and 
treatment, expect 3–7 days of hospitalization 
with severe illness.
• Some cats develop pleural effusion and 
require thoracocentesis.
• Cats that survive will return to normal 
within 2–4 weeks of discharge and appear 
immune to reinfection.
• Some cats remain persistently infected with 
the intraerythrocytic form without overt 
signs.
• Without treatment, most cats with acute 
cytauxzoonosis have died within 5 days of 
• No known risk to humans.
• Cannot be directly transmitted to another 
cat except by blood or tissue inoculation.
Cohn LA, Birkenheuer AJ, Brunker JD, et al. 
Efficacy of atovaquone and azithromycin or 
imidocarb dipropionate in cats with acute 
cytauxzoonosis. J Vet Intern Med 2011, 
25(1):55–60.
Reichard MV, Thomas JE, Arther RG, et al. 
Efficacy of an imidacloprid 10%/flumethrin 
4.5% collar (Seresto®, Bayer) for preventing 
the transmission of Cytauxzoon felis  to 
domestic cats by Amblyomma americanum . 
Parasitol Res 2013, 112(Suppl. 1):11–20.

Canine and Feline, Seventh Edition  357
D   BASICS
• Partial or complete hearing loss.
• T wo forms:
◦ Sensorineural deafness—caused by 
damage to receptors in cochlea, cochlear 
nerve, or auditory pathways in CNS.
◦ Conduction deafness—caused by 
inability to conduct sound vibration 
through external to inner-ear structures.
Sensorineural Deafness
• Hereditary—breed-related cochlear 
degeneration closely associated with the 
recessive alleles of the piebald locus and the 
dominant allele of the merle locus in dogs 
and with the dominant allele of the white 
locus in cats. These genes alter the ability of 
neural crest melanocytes to populate regions 
of the body including skin, hair, iris, ocular 
tapetum, and portions of the cochlea. The 
absence of melanocytes in the stria vascularis 
of the cochlea is associated with early 
postnatal degeneration of this structure. Can 
also be non-pigment-associated and in some 
cases also affect the vestibular system, such as 
in Doberman pinschers (associated with a 
mutation in the PTPRQ gene).
• Acquired—cochlear degeneration due to 
chronic infection, ototoxicity, neoplasia, 
chronic exposure to loud noises, anesthesia-
associated, or age-related loss of hair cells and 
spiral ganglion cells (presbycusis).
Conduction Deafness
• Congenital defects in external ear canal, 
tympanic membrane, or ossicles that transmit 
vibration in middle ear are rare. Hereditary 
predisposition in primary secretory otitis 
media in the cavalier King Charles spaniel.
• Acquired defects resulting in stenosis/
obstruction of external ear canal, rupture of 
tympanic membrane, or fusion of bony 
ossicles; most commonly associated with 
chronic otitis or middle ear polyps.
Nervous—inner ear.
GENETICS
Genetics of congenital deafness not fully 
understood, although strong association with 
the piebald and the merle locus in dogs and 
dominant white locus in cats (pigment-associ-
ated genes related to coat color).
Prevalence of congenital deafness in one or 
both ears available for the following breeds—
Dalmatian: 30% in United States, 18% in 
UK, 17% in Switzerland, 20% in Germany; 
Jack Russell terrier: 4% in United States; 
Australian cattle dog: 15% in United States, 
10% in Australia; English bull terrier: 11% (20% if white) in UK; English setter: 8% in 
United States; English cocker spaniel: 7% in 
United States; border collie: 2–3% in UK; 
purebred white cats: 20% in United States 
and Germany; non-purebred white cats: 50% 
in UK and United States.
Prevalence for different breeds varies between 
countries.
• Breed-related congenital cochlear degenera-
tion described in >90 breeds of dogs. Most 
breeds have a large amount of white pigmen  - 
tation associated with merle or piebald genes, 
except for Doberman pinscher, puli, 
Shropshire terrier. Congenital sensorineural 
deafness present by 6 weeks of age, although 
has late onset in border collie (5 years) and 
Rhodesian ridgeback (4–12 months).
• No association with gender. Dogs with blue 
iris color have a higher incidence of congeni-
tal deafness.
• Mixed-breed cats with white hair coat and 
blue irises—high incidence of deafness. 
Purebred white cats that carry the Siamese 
gene for blue eyes have a lower incidence of 
congenital deafness.
• Acquired deafness may occur in any breed 
or age of dog and cat.
SIGNS
• Unilateral deafness often goes unnoticed. 
Rarely, dogs have difficulty localizing sound.
• With bilateral disease, animals do not 
respond to auditory cues such as calling their 
name or rattling food dish. Often they are 
easily startled. Commonly have heightened 
response to vibration and visual cues.
CAUSES
• Genetic etiology likely in neonates.
• Acquired cochlea and cochlear nerve 
damage—infectious (otitis interna), neoplasia 
of bony labyrinth or nerve, trauma (physical 
or noise), systemic or topically applied drugs 
or toxins (antibiotics: aminoglycosides, 
polymyxin, erythromycin, vancomycin, 
chloramphenicol; antiseptics: ethanol, 
chlorhexidine, cetrimide; antineoplastics: 
cisplatin, carboplatin; diuretics: furosemide; 
heavy metals: arsenic, lead, mercury; 
miscellaneous: ceruminolytic agents, 
propylene glycol, salicylates), presbycusis, 
anesthesia-induced.
• Otitis externa and other external ear canal 
disease (e.g., stenosis of canal, foreign bodies, 
neoplasia, or ruptured tympanum).
• Otitis media, middle-ear polyps, primary 
secretory otitis media.
• Merle, piebald gene, or white coat color; 
blue eye color.• Chronic otitis externa, media, or interna.
• Use of ototoxic drugs.
• General anesthesia.
  DIAGNOSIS
• Early age of onset—suggests congenital 
causes in predisposed breeds.
• Use of ototoxic drugs, recent anesthesia, or 
chronic ear disease—suggests acquired causes.
• Evaluate for brain disease.
• Bacterial culture and sensitivity of ear canal 
if otitis externa.
• Myringotomy with culture of aspirates if 
otitis media.
IMAGING
• Tympanic bullae and skull radiographs—
may show soft tissue opacity and bone 
remodeling of tympanic bulla; often unre -
markable in cases with otitis media/interna.
• Ultrasound of tympanic bullae—may show 
anechoic content in cases with otitis media/
interna, but low sensitivity.
• CT/MRI—higher sensitivity for middle–
inner ear disease and intracranial pathology.
• Brainstem auditory evoked response 
(BAER)—gold standard test for evaluation of 
hearing. Measures electrical response of cochlea 
and auditory pathways in the brain to an 
auditory stimulus; reliable to identify dogs 
with unilateral disease or partial hearing loss. 
Bone conduction stimulation can be useful to 
distinguish sensorineural from conduction 
deafness. Can be used to determine the 
hearing threshold.
• Otoacoustic emissions (OAEs)—low-level 
sounds produced by inner ear as part of the 
normal hearing process that can be measured 
by placing a probe containing a microphone 
in the external ear canal. T wo forms have been 
used in dogs for assessment of sensorineural 
deafness—transient evoked OAEs (TEOAEs) 
and distortion product OAEs (DPOAEs). 
OAE is best suited for cases with congenital 
deafness, as it tests outer hair cell function and 
is not affected by inner hair cell, synapse, or 
cochlear nerve deficiencies. DPOAEs may 
show benefits in assessing age-related and 
noise-induced hearing loss and may reduce 
cost and testing times in congenital sensori -
neural deafness compared to BAER.
• Congenital deafness—degeneration of the 
stria vascularis with subsequent collapse of 
membranous labyrinth structures. Bony 
labyrinth remains intact.Deafness

358  Blackwell’s Five-Minute Veterinary Consult  
D• Acquired deafness—related to primary 
disease such as otitis or neoplasia.
• Ototoxicity—degeneration of otic hair 
cells, cochlear nerve degeneration, and loss of 
stria vascularis.
  TREATMENT
Deaf animals may be functional pets, but 
require patience, specialized training, and 
extra protection from traffic.
• Directed toward acquired causes; congenital 
deafness irreversible.
• Otitis externa, media, or interna—medical 
or surgical approaches depend on culture and 
sensitivity test results, response to antibiotics, 
and imaging findings. Conduction may 
improve as otitis externa or media resolves.• Cochlear implants can be used in dogs with 
moderate to profound deafness, but only 
preliminary data available and very expensive.
• None for congenital deafness.
• T reat otitis based on culture and sensitivity 
results.
• Aminoglycosides or other ototoxic drugs— 
use with caution.
• Topical treatment of external ear canal—
avoid if tympanic membrane is ruptured.
  FOLLOW-UP
As needed for management of otitis.POSSIBLE COMPLICATIONS
Deaf dogs need protected environments and 
training to be functional pets.
Dogs homozygous for recessive merle gene 
can be blind and sterile.
• BAER = brainstem auditory evoked 
response.
• DPOAE = distortion product OAE.
• OAE = otoacoustic emission.
• TEOAE = transient evoked OAE.
Author  Rita Gonçalves
available onlineDeafness  (continued)

Canine and Feline, Seventh Edition  359
DDeciduous Teeth, Persistent (Retained)
  BASICS
OVERVIEW
• A persistent (retained) deciduous tooth is 
one that is still present when the permanent 
tooth begins to erupt or has fully erupted. 
• Numerous factors influence the exfoliation 
of deciduous teeth—lack of a permanent 
successor; ankylosis of the deciduous crown 
or root to the alveolus; failure of the developing 
permanent crown to contact the deciduous 
root, preventing resorption of the deciduous 
root during eruption.
• More common in dogs than cats. • More 
common in small-breed dogs (e.g., Maltese, 
poodle, Yorkshire terrier, Pomeranian, etc.).  
• Occurs during permanent tooth eruption 
phase, which begins at 3 months of age for 
incisors and 5–7 months of age for canine 
teeth and molars. • Persistent deciduous teeth 
may not be detected or diagnosed until later 
in life. • No sex predilection.
SIGNS
• Persistent deciduous teeth can cause the 
permanent teeth to erupt in an abnormal 
position resulting in a malocclusion; early 
recognition and intervention are essential. 
• Maxillary canine teeth erupt mesial (rostral) 
to the persistent deciduous canine teeth; this 
can result in a diastema (space) between the 
maxillary canine tooth and the third incisor 
that is too narrow to accommodate the crown 
zcanine position is referred to as mesiover-
sion.  •  Mandibular canine teeth erupt 
lingual to the persistent deciduous teeth; this 
can result in a narrow space between the 
lower canines resulting in impingement on 
the soft tissue of the hard palate. The 
mandibular canine position is referred to as 
linguoversion.  •  All permanent incisors 
erupt lingual to the persistent deciduous 
incisors; this can result in a rostral crossbite.
• Presence of a deciduous tooth with the 
permanent tooth erupting or fully erupted. 
• Abnormal position of the permanent tooth 
due to persistence of the deciduous tooth. 
• Oral malodor from accumulation of debris 
and plaque due to crowding of the permanent 
tooth and the persistent deciduous tooth. 
• Local gingivitis and periodontal disease due to 
plaque accumulation from crowding. 
• Oronasal fistula from linguoversion of the 
permanent mandibular canine teeth. •  Deciduous 
tooth crown is usually smaller than the permanent 
tooth. •  Deciduous tooth might not have an 
underlying permanent tooth, and will often 
remain intact and vital.CAUSES & RISK FACTORS
• Cause is unknown, but is suspected to have 
a genetic basis. •  Small-breed dogs are 
  DIAGNOSIS
• Supernumerary teeth. •  Gemination of the 
crown.
N/A
IMAGING
Intraoral Radiography
• Distinguish between permanent tooth and 
deciduous tooth. •  Provide evidence or extent 
of root resorption of the deciduous tooth. 
• Identify dental abnormalities prior to 
extraction, including persistent deciduous 
tooth with no permanent successor, retained 
root with crown missing, and unerupted 
permanent tooth. •  Identify relationship of 
deciduous root and permanent crown prior to 
extraction.
• Complete oral examination—chart oral 
cavity to indicate presence of persistent 
deciduous teeth, malpositioned teeth, missing 
teeth, soft tissue trauma, and other oral 
abnormalities. •  Appropriate preoperative 
diagnostics prior to procedure to include 
intraoral radiography.
N/A
  TREATMENT
Client Education
• Persistent deciduous teeth may be prevalent 
in certain breeds. •  Start looking at teeth 
from the first puppy or kitten visit. •  Inform 
owners that you will be evaluating for 
exfoliation of deciduous teeth as well as for 
proper eruption of permanent teeth.
• Extract the deciduous tooth as soon as the 
permanent tooth has erupted through the 
gingiva. •  Pain management - local/regional 
and systemic. •  Intraoral radiographs. 
• General anesthesia with endotracheal tube 
in place and cuff inflated. •  Elevation of 
deciduous tooth. •  Careful, gentle elevation 
is critical; excessive force or pressure can 
damage the developing permanent tooth (and 
other underlying structures). •  A fractured or 
retained root may need to be removed with a 
gingival flap. •  If a permanent tooth has erupted in an abnormal position, full root 
extraction of the deciduous tooth is necessary. 
• If the deciduous root has undergone 
resorption, it may not need to be extracted. 
• Topical oral antimicrobial rinse prior to 
extraction. •  Pain management prior to, 
during, and following extraction.
N/A
  FOLLOW-UP
• After surgery, restrict activity for the rest of 
the day. •  Analgesia (nonsteroidal anti-inflam -
matory drug [NSAID]) for 24–36 hours 
postop. •  Soft diet for 3 days—canned food or 
moistened dry kibble. •  No chew toys for 
3 days; no “tug of war” for 1 week. •  Oral 
chlorhexidine rinse for 3–5 days. •  Continue 
daily tooth brushing after 24 hours.
May be prevalent in certain breeds and 
lines—avoid similar breeding.
• Malocclusion that results after full eruption 
of permanent teeth may require treatment. 
• Linguoversion of one or both mandibular 
canine teeth. •  Mesioversion of one or both 
maxillary canine teeth.
• Once extracted, there should be no further 
problems. •  Resulting malocclusion needs 
further evaluation. •  Gingiva generally heals 
uneventfully.
SEE ALSO
Malocclusions—Skeletal and Dental.
http://www.avdc.org/avdc-nomenclature
Lobprise HB, Dodd JR eds. Wiggs’s Veterinary 
Dentistry: Principles and Practice, 2nd. 
Hoboken, NJ, Wiley-Blackwell; 2019.
Author  Randi Brannan
Consulting Editor  Heidi B. Lobprise

360  Blackwell’s Five-Minute Veterinary Consult  
DDeep Cutaneous Mycoses
  BASICS
• Fungal infections that may secondarily 
disseminate by hematogenous route to the 
skin.
• Most often caused by cryptococcosis, 
blastomycosis, and coccidioidomycosis.
Cryptococcosis
Main route of infection is inhalation and 
colonization of nasal mucosa, followed by 
hematogenous spread to lymph nodes, skin, 
bones, and CNS.
Blastomycosis
• Infection by inhalation of spores 
produced from mycelial growth in the 
• Spores settle in airways, transform into 
yeast forms, and establish a primary infection 
of the lungs, followed by dissemination via 
blood and lymphatic vessels.
• Colonize lymph nodes, skin, eyes, bones, 
CNS, and testes.
Coccidioidomycosis
• Infection by inhalation of arthroconidia.
• In the lungs, arthroconidia transform into 
spherules filled with endospores, which 
disseminate by hematogenous routes to 
bones, skin, eyes, heart, testes, CNS, liver, 
and kidneys, among others.
Systemic infections via inhalation with 
hematogenous dissemination to multiple 
organs—skin, lymph nodes, eyes, bones, 
CNS, testes.
GENETICS
N/A
• Uncommon diseases,
• Incidence depends on geographic location; 
can be very high (e.g., coccidioidomycosis in 
areas of Arizona).
• C. neoformans  worldwide distribution.
• C. gattii  associated with tropical and 
subtropical climates.
• Recognized also in North America and 
British Columbia (Vancouver Island).
Areas of the United States and Canada 
surrounding the Ohio and Mississippi River 
valleys, the Great Lakes, and the Saint 
Lawrence River.
Southwestern United States, Mexico, and 
areas of Central and South America.SIGNALMENT
• Young dogs and cats; more common in 
cats.
• Siamese, Birman, and ragdoll cats
• Doberman pinscher, German shepherd 
dogs, and cocker spaniels.
• Young dogs (1–3 years); rare in cats.
• Doberman pinscher.
• Increased incidence in male dogs
• Young dogs; rare in cats.
• Boxer and Doberman pinscher predisposed.
• Increased incidence in males.
SIGNS
• Nonspecific clinical signs (asthenia, weakness, 
anorexia, weight loss), respiratory signs, or the 
appearance of skin lesions in the animal.
• Upper respiratory signs—cryptococcosis 
and blastomycosis.
• Lameness—coccidioidomycosis.
Physical Examination Findings (Skin)
• Cat—multiple papules, nodules, abscesses, 
and ulcers; bridge of nose/dorsal muzzle 
(primary site) or any skin ara; lesions may 
drain a serous exudate.
• Dog—papules, dermal-subcutaneous 
nodules or ulcers; located on any portion of 
the integument, lips, tongue, or claw beds.
Dog—draining tracts and abscesses in 
one-third of cases; Planum nasale , face, and 
claw bed most frequent locations.
Dog—dermal nodules that progress to 
abscesses and ulcers, or draining tracts over 
sites of infected bone; Coccidioides  infection 
may also be asymptomatic.
CAUSES
• Dimorphic fungi.
• Filamentous form in the environment.
• Yeast phase in mammalian tissues.
• Genus Cryptococcus  includes 40 species—
most infections in dogs and cats caused by 
C. neoformans  and C. gattii .
• C. neoformans  often found in soils 
associated with bird excrement.
• C. gattii  found in soils, especially in those 
covered with leaves of some tree species 
(eucalyptus), and in the bark of some trees 
(oak, maple, cedar).
• Dimorphic fungus.
• Mycelial form lives in moist soil and in 
decomposing organic matter such as wood 
and leaves.• Yeast form in the mammal host causes 
disseminated infection.
• Dimorphic saprophytic fungi.
• Found in sandy, alkaline soils with high 
• Main infectious species Coccidioides immitis  
and C. posadasi .
• Immunosuppressed hosts are more predis  - 
posed to develop cryptococcosis caused by C. 
neoformans .
• Living in or visiting endemic areas increases 
risk of cryptococcosis ( C. gattii ), blasto -
mycosis, and coccidioidomycosis.
  DIAGNOSIS
• Deep staphylococcal pyoderma.
• Nocardiosis.
• Actinomycosis.
• Mycobacterial infections.
• Pseudomycetoma (cat).
• Chromoblastomycosis.
• Pheohyphomycosis.
• Hyalohyphomycosis.
• Sterile nodular panniculitis.
• Sterile pyogranuloma syndrome.
• Generally nonspecific—nonregenerative 
anemia, leukocytosis, monocytosis, 
• Serum biochemical profile may reflect 
specific organ involvement; hypoalbumine-
mia and hyperglobulinemia common.
• Detection of cryptococcal polysaccharide 
capsular antigen in serum using a latex 
agglutination technique.
• Organism can be cultured in Sabouraud 
agar from skin lesions.
Measuring antibodies in serum (agar gel 
immunodiffusion [AGID], ELISA) assists in 
diagnosis of blastomycosis when organisms 
cannot be specifically identified in cytologic 
or histologic specimens.
• Conclusively diagnosed by cytologic or 
histologic visualization of the organism.
• Detection of antibodies (AGID, ELISA) 
commonly used when the organism cannot be 
demonstrated in cytology or biopsy samples.
• Coccidioides  grows in common culture 
media.

Canine and Feline, Seventh Edition  361
D• Exposure to mycelial growth in cultures a 
potential hazard to humans—organism 
should not be cultured outside of qualified 
laboratories with proper warning of the 
differential diagnosis.
IMAGING
• Radiographs-- evaluate for the presence 
of lesions in the upper airways, lungs,  
and bones.
• Ultrasound imaging—to evaluate for the 
presence of lesions in the abdominal cavity.
• Cytologic evaluation of all cutaneous 
lesions (papules, nodules, abscesses) by 
fine-needle aspirate of solid lesions or 
impression smears of exudates.
• Cytologic preparations usually reveal a 
pyogranulomatous exudate with the presence 
of the causal organism.
• Cryptococcosis—number of organisms is 
very high and they are easily detected.
• Blastomycosis and coccidioidomycosis—
detection of the fungal elements more 
difficult. If cytologic preparations are 
inconclusive, a skin biopsy for histopatho-
logic examination should be obtained.
• Histologically, these diseases are character-
ized by a nodular to diffuse pyogranuloma-
tous dermatitis and panniculitis, with the 
presence of the causal organisms.
Chronic pyogranulomatous reaction with the 
presence of organisms in tissues.
  TREATMENT
Outpatient medical management, unless 
severe internal lesions (meningoencephalitis, 
severe kidney disease).
N/A
ACTIVITY
Normal activity.
DIET
N/A
Owners should be informed of the risk 
involved in visiting areas where these 
infections are endemic.
Surgical excision of large tissue masses infected 
with Cryptococcus  (skin nodules, lymph nodes, 
nasopharyngeal masses) when possible.  MEDICATIONS
• Itraconazole (5 mg/kg PO q12–24h).
• Fluconazole (10 mg/kg PO q12–24h).
• T reatment maintained for 6–18 months—
until resolution of clinical disease.
• Some authors recommend continued 
antifungal therapy until the cryptococcal 
antigen is zero.
• T reatment continued for at least 60 days 
and at least 1 month after all signs of disease 
have resolved.
• T reatment is prolonged—treat for at least 
1 year and/or until resolution of clinical 
disease.
N/A
Azole antifungals, especially ketoconazole, are 
inhibitors of cytochrome P450 (CYP) and 
can increase serum levels of other drugs that 
are metabolized by this route (e.g., cyclosporine).
Amphotericin B and flucytosine for CNS 
and/or resistant infection.
Amphotericin B for resistant infection.
• Ketoconazole (5–10 mg/kg PO q12–
24h)—if fluconazole or itraconazole is not 
• Side effects more common and more severe 
with ketoconazole than with the other two 
azoles in cats.
• Ketoconazole is hepatotoxic and should not 
be prescribed to patients with liver damage.
• Amphotericin B is nephrotoxic and is 
contraindicated in patients with kidney damage.
  FOLLOW-UP
The frequency of monitoring depends on the 
severity and location of the lesions.PREVENTION/AVOIDANCE
Avoid visiting areas where these infections are 
endemic.
N/A
• Prognosis is guarded; depends on the 
affected organs.
• Poor prognosis with CNS involvement in 
cryptococcosis.
N/A
• Cryptococcosis, blastomycosis, and 
coccidioidomycosis are not considered 
zoonoses.
• Infected dogs and cats pose no public 
health threat because infective forms are not 
produced in tissues.
• Handling mycelial cultures of the organism 
in the laboratory is dangerous.
PREGNANCY/FERTILITY/
BREEDING
• Vertical transmission of cryptococcosis and 
blastomycosis has been reported in humans—
considered extremely rare and not reported in 
• Intrauterine transmission of coccidioidomy-
cosis not likely to occur because of the large 
size of the spherules.
SYNONYMS
• Cryptococcosis—torulosis, European 
• Blastomycosis—Gilchrist disease, Chicago 
disease.
• Coccidioidomycosis—valley fever, San 
Joaquín Valley fever.
https://www.cdc.gov/fungal
Greene CG. Infectious Diseases of the Dog and 
Cat, 4th ed. St. Louis, MO: Elsevier, 2012.
Five-Minute Veterinary Consult 
Dermatology, 3rd ed. Hoboken, NJ: 
Wiley-Blackwell, 2018.
Author  Lluís Ferrer
Resnick(continued)  Deep Cutaneous Mycoses

362  Blackwell’s Five-Minute Veterinary Consult  
DDemodicosis
  BASICS
An inflammatory parasitic disease of dogs and 
cats characterized by an increased number of 
demodectic mites in the hair follicles and on 
the epidermis.
Dogs
• Three species of mites identified in the dog:
◦ Demodex canis —follicular mite; part of the 
normal fauna of the skin; typically present in 
small numbers; resides in the hair follicles and 
sebaceous glands of the skin, transmitted from 
the mother to the neonate during the first 2–3 
days of nursing.  ◦ Demodex injai —large, 
long-bodied mite found in the pilosebaceous 
unit, mode of transmission unknown; only 
associated with adult-onset disease, with highest 
incidence noted in the terrier breeds often 
along the dorsal midline (West Highland white 
terrier and wirehaired fox terrier). ◦ Demodex 
cornei —lives in the stratum corneum of the 
epidermis; mode of transmission unknown; 
most likely a morphologic variant of D. canis .
• Proliferation of mites may be the result of 
immunologic disorder, either genetic or 
iatrogenic.  • Pruritus occurs when a 
secondary bacterial infection is present.
Cats
• T wo species of mites identified in the cat:
◦ Demodex gatoi —contagious; can be asympto  - 
matic, but most commonly is associated with 
pruritic dermatitis leading to self-trauma, 
alopecia, and barbering. ◦ Demodex cati—  often 
associated with immunosuppressive and 
metabolic disease; these mites cause folliculitis 
and alopecia, but are rarely pruritic.
Skin/exocrine.
GENETICS
Initial proliferation of mites may be the result 
of a genetic disorder.
• Dogs— D. canis  is very common. • Cats—
depending on geographic location, D. gatoi  
may be common or rare; D. cati  is rare.
Species
• D. canis —American Staffordshire terrier, 
shar-pei, Boston terrier, English bulldog, and 
West Highland white terrier. • D. injai—
West Highland white and wirehaired fox 
terriers, shih tzu.  • Potential increased 
incidence in Siamese and Burmese cats.
• Juvenile onset, localized—usually in dogs 
<1 year of age; median 3–6 months, typically <5 lesions.  • Generalized—both young and 
old animals.  • D. cati  may be more common 
in middle-aged or older cats; D. gatoi  seems 
to be more common in younger cats and 
kittens, but any age can be affected.
SIGNS
Dogs
• Patchy alopecia—most common site is the 
face, especially around the perioral and 
periocular areas and forelegs; may also be seen 
on the trunk and feet.  • Pododemodicosis—
lesions localized to the feet.  • Disease can 
progress to become or begin with a general-
ized distribution.  • Usually not pruritic 
unless secondarily infected.  • Hair follicles 
distended with large numbers of mites, lose 
hair and develop secondary bacterial 
folliculitis, followed by rupturing of the 
follicles (furunculosis).  • With progression, 
the skin becomes severely inflamed, exuda-
tive, and granulomatous.  • D. injai  may be 
associated with greasy seborrheic dermatitis of 
the dorsal trunk, comedones, erythema, 
alopecia, and hyperpigmentation.
Cats
• D. cati —partial to complete alopecia of the 
eyelids, periocular region, head, neck, flank, 
and ventrum.  • D. gatoi —pruritus with 
dramatic scaling, erythema, and/or crusting 
due to inflammation and self-trauma.  
• Ceruminous otitis externa has been 
reported.  • D. cati  often associated with 
immunosuppressive disease.
CAUSES
• Dog— D. canis , D. injai , and D. cornei .
• Cat— D. cati  and D. gatoi .
Dogs
• Exact immunopathologic mechanism 
unknown.  • Dogs with generalized demodi -
cosis may have abnormal or depressed T-cell 
function.  • Development associated with 
oclacitinib treatment.  • Genetic factors (especially 
juvenile onset), immunosuppression, and/or 
metabolic diseases may predispose animal.
Cats
• D. cati —often associated with metabolic 
diseases that affect the immune system (e.g., 
feline immunodeficiency virus [FIV], hyper- 
adrenocorticism, diabetes mellitus).  
• D. gatoi —considered contagious; cats in 
contact with other cats are at risk.
  DIAGNOSIS
Dogs
• Bacterial folliculitis/ 
furunculosis. • Dermatophytosis. • Any 
cause of inflammatory alopecia.Cats
• Allergic dermatitis. • Dermatophytosis. 
• Any cause of alopecia or pruritus.
Normal unless there is an underlying 
process.
• Feline leukemia virus (FeLV) and FIV 
serology. • Fecal samples—rare finding of 
mites in feces; more common with cats.
• Skin scrapings diagnostic for finding mites 
in most cases— D. gatoi  may be difficult to 
find. • Hair plucking can be used in areas 
such as eyelids. • Skin biopsy—may be 
needed when lesions are chronic, granuloma-
tous, and fibrotic (especially on the foot); 
may be needed to diagnose demodicosis in 
the shar pei breed.
  TREATMENT
• Localized D. canis  lesions often (90%) 
resolve spontaneously. • Evaluate the health 
status of patients presenting with generalized 
lesions of demodicosis.
• Localized—most cases resolve spontane -
ously. • Generalized—frequent manage -
ment problem due to chronicity. Juvenile 
onset considered to have an inheritable 
predisposition—breeding of affected 
animals is not recommended.
Dogs
Isoxazolines antiparasitics
• T reatment of choice —excellent efficacy 
against demodicosis at label doses for fleas; 
safe for avermectin-sensitive dogs. • Side 
effects uncommon—vomiting, diarrhea, 
inappetence, or neurologic signs including 
seizures.
Ivermectin
• 0.3–0.6 mg/kg q24h PO very effective; 
initiate therapy with a test dose of 0.12 mg/
kg q24h for first week to observe for any signs 
of sensitivity.  • T reat for 30–60 days beyond 
negative skin scrapings (average 3–8 months).  
• Non-FDA-approved usage—do not use in 
avermectin-sensitive (ABCB-1 mutation) 
breeds.
Milbemycin Oxime
• 1–2 mg/kg PO q24h cures 50% of cases; 
2 mg/kg PO q24h cures 85% of cases.

Canine and Feline, Seventh Edition  363
D• ABCB-1 mutation individuals may have 
neurologic signs with higher doses; tolerate 
milbemycin better than other drugs in this class.  
• Non-FDA-approved usage.
Moxidectin
• 0.3 mg/kg PO q24h or topical application 
once weekly. • Non-FDA-approved usage—
do not use in avermectin-sensitive (ABCB-1 
mutation) breeds.
Amitraz
• Applied in the United States as a 250 ppm 
(0.025%) dip every 14 days and in Europe as a 
500 ppm (0.05%) dip every 7 days. See adverse 
effects below.  • Clipping the hair coat and 
bathing with a benzoyl peroxide shampoo before 
application of the rinse assist response.  • Amitraz-
containing collars and spot-ons are not effective.  
• Efficacy is proportional to the frequency of 
administration and the concentration of the rinse.  
• Poor compliance limits efficacy.  • 11% and 
30% of cases will not be cured; may need to try 
an alternative therapy or control with mainte -
nance rinse every 2–8 weeks.
Cats
Isoxazoline antiparasitics
• T reatment of choice at label doses for fleas. 
• Side effects uncommon but include 
drooling, vomiting, diarrhea, inappetence, or 
neurologic signs including seizures.
2% lime sulfur
• Can be diluted, sponged over the cat, and 
allowed to dry without rinsing once weekly 
for 6 treatments.  • Malodorous, staining, and 
difficult to apply to the face.  • Patient should 
be restricted from grooming after application.
Alternatives
Alternative but less effective options for the 
treatment of D. gatoi :
• Milbemycin oxime—1 mg/kg PO q24h.
• Doramectin—0.6 mg/kg SC weekly
• Ivermectin—0.2–0.3 mg/kg PO q24–48h. 
Neurologic side effects such as ataxia are 
possible with ivermectin.
Do not use ivermectin in avermectin-sensitive 
breeds—collies, Shetland sheepdogs, Old 
English sheepdogs, Australian shepherds, 
other herding breeds, and crosses with these 
breeds. Screening for the ABCB-1 mutation 
Amitraz
• Side effects—somnolence, lethargy, 
depression, anorexia seen in 30% of patients for 12–36 hours after treatment.  • Rare side 
effects—vomiting, diarrhea, pruritus, polyuria, 
mydriasis, bradycardia, hypoventilation, 
hypotension, hypothermia, ataxia, ileus, 
bloat, hyperglycemia, convulsions, death.  
• Yohimbine at 0.11 mg/kg IV is an antidote, 
as is atipamezole.  • Incidence and severity of 
side effects do not appear to be proportional 
to dose or frequency of use.  • Apply in a 
well-ventilated area; owners should wear 
aprons and gloves so they do not come in 
contact with the dip.  • Human beings can 
develop dermatitis, headaches, and respiratory 
difficulty after exposure. Amitraz should not 
be used by people taking monoamine oxidase 
(MAO) inhibitors (e.g., some antihistamines, 
antidepressants, and antihypertensives). 
• Can dysregulate blood sugar in diabetics.
Ivermectin and Milbemycin
Signs of toxicity—salivation, vomiting, 
mydriasis, confusion, ataxia, hypersensitivity to 
sound, weakness, recumbency, coma, and death.
• Amitraz—may interact with heterocyclic 
antidepressants, xylazine, benzodiazepines, 
and macrocyclic lactones.  • Ivermectin and 
milbemycin—cause elevated levels of mono  - 
amine neurotransmitter metabolites, which 
could result in adverse drug interactions with 
amitraz and benzodiazepines.  • Spinosad and 
other drugs in that class are contraindicated 
with ivermectin therapy.
  FOLLOW-UP
Repeat skin scrapings and evidence of clinical 
resolution are used to monitor progress, 
generally repeated every 2–4 weeks until 
resolution, and then treatments are continued 
1–2 months beyond negative scrapings.
Do not breed animals with generalized 
disease.
Secondary bacterial folliculitis and 
Prognosis is very good for elimination of the 
demodicosis with isoxazoline treatment. 
Prognosis depends heavily on compliance, 
and genetic, immunologic, and underlying 
diseases. Severe, generalized cases with 
underlying disease may be refractory to 
treatments other than isoxazoline.  MISCELLANEOUS
• Adult-onset demodicosis—sudden 
occurrence is associated with internal disease, 
malignant neoplasia, and/or immunosuppres-
sive disease; approximately 25% of cases are 
idiopathic over a follow-up period of 1–2 
years. • D. cati  associated with FeLV, FIV, 
toxoplasmosis, iatrogenic immune suppres-
sants, papillomaviral plaques, and systemic 
lupus erythematosus (SLE).
Young dogs are often predisposed to a 
localized form.
None
Do not breed animals with the generalized 
form.
SYNONYMS
• Mange. • Red mange.
SEE ALSO
Ivermectin and Other Macrocyclic Lactones 
• FIV = feline immunodeficiency virus. 
Sastre N, Ravera I, Villanueva S, et al. 
Phylogenetic relationships in three species 
of canine Demodex  mite based on partial 
sequences of mitochondrial 16S rDNA. Vet 
Derm 2012, 23(6):509–e101.
Resnick
available online(continued)  Demodicosis

364  Blackwell’s Five-Minute Veterinary Consult  
DDental Caries
  BASICS
OVERVIEW
• Caries is the decay of the dental hard tissues 
(enamel, cementum, and dentin) due to the 
effects of oral bacteria on fermentable 
carbohydrates on the tooth surface.
• The word “caries” is Latin for rottenness 
and is both the singular and plural form.
• Oral bacteria ferment carbohydrates on 
the tooth surface, resulting in the produc -
tion of acids leading to demineralization of 
the hard tissues, thus allowing bacterial and 
leukocytic digestion of the organic matrix 
of the tooth.
• Caries has been very common in humans in 
“westernized” society, where diets rich in 
highly refined carbohydrates are the norm. 
Aggressive public education and preventive 
measures have resulted in a decline in 
incidence over the past several decades.
• In humans, Streptococcus mutans  is particu -
larly implicated in the development of caries.
• For various reasons (e.g., diet lower in 
refined carbohydrates, higher salivary pH, 
lower salivary amylase, conical crown shape, 
wider interdental spacing, different indig-
enous oral flora), caries is not common in the 
domestic dog, but it does occur and should 
be looked for.
• A study published in the Journal of 
Veterinary Dentistry  in 1998 (see Suggested 
Reading) reported that 5.3% of dogs 1 year of 
age or older had one or more caries lesions, 
with 52% having bilaterally symmetric 
lesions.
• Caries can affect the crown or roots of the 
teeth and is classified as pit-and-fissure, 
smooth-surface, or root caries.
• Caries occurs in dogs.
• Reported in cats; tooth resorption (feline 
odontoclastic resorptive lesions [FORL]) has 
sometimes been misnamed feline caries. To 
the author’s knowledge, there are no 
published reports of true dental caries 
occurring in the domestic cat, though it is 
theoretically possible.• There is no reported breed, age, or gender 
• Anecdotally, the author has observed a 
higher incidence of pit-and-fissure lesions in 
the occlusal tables of the maxillary first molar 
teeth in large-breed dogs such as Labrador 
retrievers and German shepherds.
SIGNS
• Incipient smooth-surface caries—appears as 
an area of dull, frosty-white enamel.
• Clinical caries—appears as a structural 
defect on the surface of the crown or root.
• The defect is frequently filled with or lined 
by dark, soft necrotic dentin. The defect may 
also trap and hold food debris.
• Affected dentin will yield to a dental 
explorer and can be removed with a dental 
excavator or curette.
• Caries is caused by oral bacteria fermenting 
carbohydrates on the tooth surface, leading to 
the production of acids (acetic, lactic, 
propionic) that demineralize the enamel, 
cementum, and dentin, followed by digestion 
of the organic matrix of the tooth by oral 
bacteria and/or leukocytes.
• There is a constant exchange of minerals 
between the tooth surfaces (enamel, any exposed 
dentin or root cementum) and the oral fluids; if 
there is a net loss of mineral, caries develops.
• Early (incipient) caries may be reversible 
through remineralization.
• Once the protein matrix collapses, the 
lesion is irreversible.
• Any factors that allow prolonged retention 
of fermentable carbohydrates and bacterial 
plaque on the tooth surface predispose to the 
development of caries.
• A deep occlusal pit on the maxillary first 
molar is the most common place for caries to 
develop.
• Dental surfaces in close contact with an 
established caries are at risk of developing a 
lesion by extension.
• Deep occlusal pits and developmental 
grooves on the crown surface predispose to 
pit-and-fissure caries.
• Tight interdental contacts predispose to 
smooth-surface caries.• Deep periodontal pockets predispose to 
root caries.
• Animals with poorly mineralized enamel, 
lower salivary pH, diets high in fermentable 
carbohydrates, and poor oral hygiene are at 
risk of developing caries.
• Loss of enamel through any means (hypo  - 
calcification at the developmental stage, 
abrasive wear or attrition, traumatic fracture) 
that exposes the softer, underlying dentin may 
increase the risk for the development of caries.
  DIAGNOSIS
• Crown fracture, abrasive wear or attrition 
with exposed tertiary dentin, or extrinsic 
staining.
• Enamel hypocalcification with exposed and 
stained dentin.
• Tooth resorption (FORL) has been misnamed 
feline caries in the past.
• Tooth resorption can also occur in dogs and 
may be mistaken for caries.
• Sound dentin is hard and will not yield to a 
dental explorer, whereas carious dentin is soft 
and will yield to a sharp instrument.
• Root caries may be confused with external 
root resorption, though the distinction would 
often be academic, as either usually indicates 
the need for extraction.
• The lesion should be staged as to the depth 
of the pathology.
• Table 1 is adapted from the American 
Veterinary Dental College approved 
nomenclature for tooth resorption as 
published on its website.
N/A
IMAGING
Intraoral Dental Radiography
• Areas of demineralization and tissue loss 
will appear as lucent areas contrasted against 
radiodense normal dental tissues.
• If the lesion has penetrated into the pulp 
chamber, there will be endodontic disease, 
and periapical disease may be evident if the 
lesion is sufficiently longstanding.
Table 1
Stage 1 Defect involves enamel or cementum only.
Stage 2 Defect extends into dentin but not into pulp chamber.
Stage 3 Deep dental hard tissue loss (cementum and/or enamel with loss of dentin that extends to the pulp cavity); most of the tooth retains its 
integrity.
Stage 4 Extensive dental hard tissue loss (cementum and/or enamel with loss of dentin that extends to the pulp cavity); most of the tooth has lost 
its integrity.
Stage 5 Majority of crown lost; root remnants remaining.

Canine and Feline, Seventh Edition  365
D• Small lesions may be difficult to demon-
strate due to superimposition of normal, 
radiodense tissues (dental and skeletal).
• Visual examination of the clean, dry tooth 
surface under good light and with the aid of 
magnification.
• Exploration with a sharp dental explorer—
the explorer will sink into carious dentin and 
stick, providing the sensation of “tug-back” 
upon withdrawal.
• Subgingival exploration—reveals irregularities 
in the root surface.
• Caries detection dyes have been used by 
human and veterinary dentists to aid in the 
differentiation between sound and carious 
dentinal tissue. However, their use may lead 
to false-positive results and overtreatment 
through the removal of excess tissue. Reliance 
on visual, tactile, and radiographic findings is 
preferable.
  TREATMENT
• Focus on prevention—examine the adult 
dentition of adolescent dogs (6–8 months of 
age) to identify anatomically compromised 
areas at risk for the development of caries. 
Deep pits in the occlusal surface of the 
maxillary first molar (for example) can be 
filled with a pit-and-fissure sealant or 
fluoride-releasing dental bonding agent to 
prevent caries development if identified prior 
to the development of any decay.
• Incipient caries—can be arrested and 
possibly reversed by application of a fluoride 
varnish or fluoride-releasing dental bonding 
agent and modification of the risk factors.
• Lesions that result in mild to moderate coronal 
tissue loss (stage 1 or 2)—remove carious dentin 
and unsupported enamel using hand instru -
ments and power rotary dental instruments, then 
restore the coronal anatomy with a bonded, 
composite restoration or prosthetic restoration.
• Lesions that extend into pulp tissue 
(stage 3)—endodontic treatment must 
precede restorative treatment. Alternatively, 
extraction may be indicated. As the pulp 
tissue in the roots will be contaminated, 
complete removal of all root remnants is 
essential if extraction is performed.• Lesions that result in extensive coronal 
tissue loss (stage 4 or 5)—extraction is 
typically the only treatment option. As the 
pulp tissue in the roots will be contami -
nated, complete removal of all root remnants 
is essential.
• Root caries—if the periodontal disease 
can be managed and the restoration placed 
supragingivally, restoration may be possible; 
however, for most teeth with root caries, 
extraction will be the treatment of choice.
• If only one root of a multirooted tooth 
is carious—extraction of the affected root 
with endodontic treatment of the remaining 
root(s) is also an option.
• For high-risk patients—application of a 
pit-and-fissure sealant and/or fluoride-
releasing dental bonding agent on remain -
ing teeth with occlusal surfaces may be 
• Postoperative broad-spectrum antibiotics—
may be indicated if there is pulp involvement 
necessitating endodontic treatment or 
• Postoperative analgesia with nonsteroidal 
anti-inflammatory drugs and/or narcotics is 
indicated following endodontic or exodontic 
treatment or extensive restorative work of 
vital teeth.
N/A
  FOLLOW-UP
• Examine and radiograph treated teeth 6 
months postoperatively, then annually or as 
the opportunity presents.
• Evaluate the integrity of the restorations, 
assess for further decay at the margins or 
under the restorations, assess for the develop  - 
ment of endodontic disease.
• As affected individuals frequently have 
more than one caries, examine all teeth carefully (clinically and radiographically) 
at any opportunity to monitor for the 
development of new lesions.
Avoidance of diet and treats high in refined 
carbohydrates may reduce the risk of the 
development of further caries.
If a lesion has been properly debrided and 
restored it should have an excellent progno -
sis. Appropriate staging and case selection, 
thorough removal of all carious tissues, and 
adherence to restorative principles are 
SYNONYMS
• Cavities.
• Dental decay.
• FORL = feline odontoclastic resorptive 
lesions.
• http://www.toothvet.ca/PDFfiles/
DentalCaries.pdf
• https://avdc.org/avdc-nomenclature
• http://www.toothvet.ca/PDFfiles/Tooth_
resorption_in_cats.pdf
• http://www.toothvet.ca/PDFfiles/RLs_in_
Dogs.pdf
Hale FA. Dental caries (cavities). In: Lobprise 
HB, ed., Blackwell’s Five-Minute Veterinary 
Consult Clinical Companion: Small Animal 
Dentistry. Ames, IA: Blackwell, 2007, pp. 
212–224.
Hale FA. Dental caries in the dog. J Vet Dent 
1998, 15:79–83.
Hale FA. Veterinary dentistry. Dental caries 
in the dog. CVJ 2009, 50:1301–1304.
McComb D. Caries-detector dyes—how 
accurate and useful are they? J Can 
Dent Assoc 2000, 66:195–198. http://
www.cda-adc.ca/jcda/vol-66/issue-
4/195.html
Author  Fraser A. Hale
Consulting Editor  Heidi B. Lobprise(continued)  Dental Caries

366  Blackwell’s Five-Minute Veterinary Consult  
DDentigerous Cyst
  BASICS
OVERVIEW
Cyst formation originating from tissue 
surrounding the crown of an unerupted tooth.
• Any breed that is at an increased risk for 
impaired eruption.
• Boxers, bulldogs—mandibular first 
premolars, often bilateral.
• Unerupted teeth at 6–7 months of age, but 
cystic development may not occur until much 
later, if at all.
SIGNS
• Cystic changes may be initially unapparent 
without diagnostic imaging.
• “Missing” tooth.
• Formation of a soft swelling at the site of a 
missing tooth, often fluctuant with fluid.
• Patient may present, with no previous 
indication of a problem, for a pathologic 
fracture of the mandible due to cystic 
destruction of the surrounding bone.
Unerupted teeth.
  DIAGNOSIS
• Odontogenic keratocyst—cyst of the jaw 
demonstrating aggressive expansion that may, 
or may not, be associated with unerupted teeth.
• Primordial cyst—cystic degeneration of a 
tooth bud before enamel/dentin formation 
(cyst without a tooth).
• Oral mass—odontoma (complex or 
compound): tooth structures (enamel, dentin, 
cementum, and pulp) sometimes contained 
within cystic structure, but with different 
levels of organization.
• T ransformation to ameloblastomas have 
been reported in humans; histologic 
evaluation of the cyst lining is highly 
• No abnormalities typically found.
• Preoperative diagnostics where appropriate 
for safe administration of general anesthesia.
IMAGING
• Definitive diagnosis from radiography.
• Radiographs are essential in any instance of 
missing or unerupted teeth.
• Radiographically—radiolucent cyst 
originating from the remnant enamel organ at 
the neck of the tooth and encompassing the 
crown (a halo).
• CT studies of the head should evaluate for 
presence of unerupted teeth.DIAGNOSTIC PROCEDURES
Histopathologic assessment if atypical 
radiographic findings (any unerupted teeth 
demonstrating radiolucency surrounding the 
unerupted crown should be submitted for 
histologic evaluation).
  TREATMENT
• Appropriate preoperative antimicrobial and 
pain management therapy when indicated.
• Appropriate patient monitoring and 
support during anesthetic procedure.
• If cystic formation is present—surgical 
extraction, complete debridement of cyst 
lining, and histologic evaluation.
• If an embedded tooth has been present in a 
mature animal—assess for any cystic structure 
or other pathologic changes involving the 
tooth; continued monitoring (minimally 
yearly) may be reasonable if surgical extraction 
would damage large amounts of bone.
• If a nonstrategic tooth can be easily 
extracted, it would be best to do so, even if 
cystic changes are not present.
Postoperative analgesics, as necessary.
N/A
  FOLLOW-UP
• Pathologic fracture may occur if dentigerous 
cyst is not diagnosed and treated.
• Fracture of mandible at time of extraction, 
due to compromised supporting bone.
• Cyst development and expansion result in 
weakening of the bone at that location and 
may risk causing root resorption or devitaliza-
tion of neighboring teeth.
• Extraction should be performed to avoid 
risk for future cyst development.
• Good with early detection and extraction.
• Fair to guarded with extensive bone 
destruction or pathologic fracture.
https://avdc.org/avdc-nomenclature Suggested Reading
Babbitt SG, Krakowski Volker M, Luskin IR. 
Incidence of radiographic cystic lesions 
associated with unerupted teeth in dogs. J 
Vet Dent 2016, 33(4):226–233.
Lobprise HB. Blackwell’s Five-Minute 
Small Animal Dentistry. Ames, IA: 
Blackwell, 2007.
Lobprise HB, Dodd JR. Wigg’s Veterinary 
Dentistry: Principles and Practice, 2nd ed. 
Ames, IA: Wiley-Blackwell, 2019.
Verstraete FJM, Zin BP , Kass PH, et al. 
Clinical signs and histologic findings in 
dogs with odontogenic cysts: 41 cases 
(1995–2010). J Am Vet Med Assoc 2011, 
239(11):1470–1476.
White SC, Pharoah MJ. Oral Radiology 
Principles and Interpretation, 5th ed. St. 
Louis, MO: Mosby, 2004, pp. 388–392.
Author  Christopher J. Snyder

Canine and Feline, Seventh Edition  367
D
Dermatomyositis
  BASICS
An inheritable inflammatory disease of the 
skin, muscles, and vasculature that develops 
in young collies, Shetland sheepdogs, and 
their crossbreeds.
• The exact pathogenesis of dermatomyositis 
is unknown.
• A familial predisposition has been reported 
in collies and Shetland sheepdogs; however, 
possible triggers for the disease include 
infectious agents (especially viral), vaccines, 
drugs, malignancy, toxins, infection—as seen 
with ischemic dermatopathy in other breeds.
• Based on the clinical and histopathologic 
evidence, an immune-mediated or auto-
immune process may be involved.
• Musculoskeletal.
GENETICS
Autosomal dominant inheritance, with 
variable expression in collies and Shetland 
sheepdogs.
Exact prevalence is unknown.
Species
Dogs
• Inheritable disease in collie, Shetland 
sheepdog and their crossbreeds, Beauceron 
shepherd, Belgian Tervuren, Rottweiler, 
kelpie, and Portuguese water dog.
• Similar symptoms reported in the mongrel, 
Welsh corgi, Lakeland terrier, chow chow, 
German shepherd dog, schipperke, and kuvasz.
• Dogs of other breeds with similar signs are 
classified as ischemic dermatopathy (dermato-
myositis-like), and not dermatomyositis as 
• Cutaneous lesions typically develop before 
6 months, and may develop as early as 7 
• Full extent of lesions usually present by 1 
year of age, and may lessen thereafter.
• Adult-onset dermatomyositis can occur, but 
is rare, and is usually less severe.
SIGNS
• Clinical signs vary from subtle skin lesions 
and subclinical myositis to severe skin lesions 
with generalized muscle atrophy, abnormal 
gait, and megaesophagus.• Several littermates may be affected, but the 
severity of the disease often varies significantly 
among affected dogs.
• Waxing and waning lesions.
• Usually seen in affected dogs before 6 
months of age.
• Begins around the eyes and lips, face, inner 
ear pinnae, tip of the tail, and bony promi-
nences—the entire face may be involved.
• Pressure points over bony prominences, 
especially the carpal and tarsal regions.
• Characterized by variable degrees of crusted 
erosions, ulcers, and alopecia, with erythema, 
scaling, and scarring.
• Foot pad and oral ulcers, as well as nail 
abnormality or loss may occur.
• Scarring—often a sequela to the initial skin 
lesions.
• Atrophy of the masseter and temporal 
muscles—severe cases may have difficulty 
eating, drinking, and swallowing.
• Stiff or high-stepping gait.
• Myositis—signs may be absent or vary from 
subtle decrease in the mass of the temporalis 
muscles to generalized symmetric muscle 
atrophy and stiff high-stepping gait.
• Dogs with megaesophagus may present 
with aspiration pneumonia.
CAUSES
• Hereditary in collies, Shetland sheepdogs, 
and their crosses.
• Infectious agents, toxins, malignancy, 
vaccines, or drugs may be a triggering event.
• Immune-mediated disease in other breeds.
Mechanical pressure and trauma, and 
ultraviolet light exposure may worsen 
cutaneous lesions.
  DIAGNOSIS
• Discoid lupus erythematosus.
• Systemic lupus erythematosus.
• Polymyositis.
• Ischemic dermatopathy.
• Epidermolysis bullosa simplex.
Serum creatine kinase may be elevated due to 
muscle damage.
• Antinuclear antibody titers—rule out 
systemic lupus erythematosus.
• Elevated levels of immunoglobulin G and 
circulating immune complex correlated with 
disease severity.DIAGNOSTIC PROCEDURES
• Skin biopsy—may be diagnostic for 
dermatomyositis, although this disease can be 
difficult to definitively diagnose; avoid 
infected and scarred lesions.
• Muscle biopsy—proper muscle selection 
can be difficult because pathologic changes 
may be mild consisting of muscle necrosis 
and atrophy.
• Electromyography (EMG)—ideally, used to 
select affected muscles for biopsy; if EMG is 
not available, atrophied muscles should be 
biopsied.
Skin Biopsy
• Scattered apoptosis or vacuolation of 
individual and follicular basal cells; may lead 
to intrabasal or subepidermal clefting.
• Mild pigmentary incontinence.
• Superficial, mild, diffuse dermal and 
perivascular cellular infiltrates—composed of 
lymphocytes, plasma cells, and histiocytes.
• Follicular atrophy and perifollicular fibrosis 
in chronic cases.
• Secondary epidermal ulceration and dermal 
scarring—may be present.
• Histopathologic features may be subtle and 
consist mostly of atrophic changes; however, 
the combination of epidermal and follicular 
basal cell degeneration, perivascular inflamm -
ation, and follicular atrophy with fibrosis is 
highly suggestive of dermatomyositis.
Muscle Biopsy
• Variable multifocal accumulations of 
inflammatory cells, including lymphocytes, 
plasma cells, macrophages, and neutrophils.
• Myofibril degeneration—characterized by 
fragmentation, vacuolation, atrophy, fibrosis, 
and regeneration.
EMG
EMG abnormalities are present especially in 
the muscles of the head and distal limbs; 
findings include fibrillation potentials (rapid, 
irregular, and unsynchronized contraction of 
muscle fibers) and positive sharp waves.
  TREATMENT
• Most dogs treated as outpatients.
• Dogs with severe myositis and megaesopha-
gus may need hospitalization for supportive 
care.
• Severe cases may warrant euthanasia.
• Assist to eat if muscles of mastication are 
affected; feed at an elevated position if 
megaesophagus develops.
• Nonspecific supportive therapy includes 
gentle bathing and soaking to remove crusts, 
and treatment of secondary bacterial folliculitis 
(if present).

368  Blackwell’s Five-Minute Veterinary Consult  
D
ACTIVITY
• Avoid activities that may traumatize the 
skin.
• Keep indoors during the day to avoid solar 
radiation.
DIET
N/A
• Discuss the hereditary nature of the disease.
• Note that affected dogs should not be bred.
• Inform the owner that the disease is not 
curable, although spontaneous resolution or 
waxing and waning of symptoms may occur.
• Discuss prognosis and possible complica-
tions, especially in severely affected dogs.
• Therapeutic efficacy of medical treatment 
can be difficult to assess because the disease 
tends to be cyclic in nature and is often 
self-limiting.
 DRUG(S) OF CHOICE
• Vitamin E 200–800 IU PO q12–24h.
• Essential fatty acid supplement.
• Prednisolone 1–2 mg/kg PO q12–24h until 
remission, then alternate-day to twice-weekly 
administration using the lowest dosage 
possible for long-term control.
• Nonsteroidal anti-inflammatory medication 
(if steroids contraindicated).
• Pentoxifylline 10–20 mg/kg PO q12h.
• Tetracycline (250 mg >10 kg, 500 mg 
<10 kg PO q8–12h), doxycycline (10 mg/kg 
q24h), minocycline (5 mg/kg q12h), with 
niacinamide (250 mg >10kg, 500 mg <10 kg 
PO q8–12h).
• Tacrolimus 0.1% applied q12h.
• Oclacitinib 0.4-0.6mg/kg BID.
• Pentoxifylline—rarely causes gastric 
irritation; can affect clotting times (pro-
thrombin time [PT]/partial thromboplastin 
time [PTT] prolongation and thrombocyto-
penia) and dogs receiving anticoagulant 
therapy should be monitored carefully when 
treated with this drug; possible rare seizure or 
reduction of seizure threshold in epileptics.
• Glucocorticoids—discuss possible side 
effects with the owner.
• Tacrolimus can cause local irritation.
Glucocorticoids and nonsteroidal anti-inflam-
matory medications can cause gastrointestinal 
bleeding if used concurrently.ALTERNATIVE DRUG(S)
N/A
  FOLLOW-UP
• Do not breed affected animals.
• Neuter intact animals to reduce hormonal 
influence on symptoms.
• Minimize trauma and exposure to sunlight.
• Secondary bacterial folliculitis.
• Mildly to moderately affected dogs may 
have residual scarring.
• Severely affected dogs may have trouble 
chewing, drinking, and swallowing due to 
scarring of the masticatory and esophageal 
muscles.
• Megaesophagus may develop, predisposing 
the dog to aspiration pneumonia.
• Dogs may be lame due to damage of the 
muscles of the extremities.
• Long-term prognosis—variable, depending 
on severity of disease.
• Minimal disease—prognosis good; tends to 
spontaneously resolve with no evidence of 
scarring.
• Mild to moderate disease—tends to resolve 
spontaneously, but residual scarring is 
common.
• Severe disease—prognosis for long-term 
survival is poor as damage to the skin and 
muscle may be lifelong.
None
• Initial clinical signs usually occur in dogs 
younger than 6 months.
• Adult onset—rare; more commonly seen in 
dogs that had subtle lesions as puppies.
None
• Do not breed affected dogs.
• Pregnancy may exacerbate clinical 
symptoms.
• Estrus may exacerbate clinical symptoms.SYNONYMS
• Familial canine dermatomyositis.
• Canine familial dermatomyositis.
• Ischemic dermatopathy in collies and 
Shetland sheepdogs.
SEE ALSO
• Lupus Erythematosus, Cutaneous 
(Discoid).
• Lupus Erythematosus, Systemic (SLE).
• EMG = electromyography, 
electromyographic.
• PTT = partial thromboplastin time.
Bresciani F , Zagnoli L, Fracassi F , et al. 
Dermatomyositis-like disease in Rottweiler. 
Vet Dermatol 2014, 25(3):229–e62.
Carlotti DN, Grucker S, Germain PA. 
Dermatomyositis in a four month old 
schipperke. Pratique Medicale et 
Chirurgicale de l’Animal de Compagnie 
2005, 40(3):141–144.
Gross TL, Ihrike PJ, Walder EJ, Affolter VK. 
Skin Diseases of the Dog and Cat, 2nd ed. 
Oxford: Blackwell Science, 2005, pp. 
49–52, 503–505.
Hargis AM, Mundell AC. Familial canine 
dermatomyositis. Compend Contin Educ 
Pract Vet 1992, 14:855–864.
Five-Minute Veterinary Consult Clinical 
2018.
Levy BJ, Linder KE, Olivry T. The role of 
oclacitinib in the management of ischemic 
dermatopathy in four dogs. Vet Dermatol 
2019, 30(3): 201–208.
Rothing A, Rufenacht S, Welle MM. 
Dermatomyositis in family of working 
Kelpies. Tierarztl Prax Ausg K Kleintiere 
Heimtiere 2015, 43(5):331–336.
Wahl JM, Clark LA, Skalli O, et al. 
Analysis of gene transcript profiling and 
immunobiology in Shetland sheepdog 
with dermatomyositis. Vet Dermatol 
2008, 19(2):52–58.
Resnick
available onlineDermatomyositis  (continued)

Canine and Feline, Seventh Edition  369
DDermatophilosis
  BASICS
OVERVIEW
• “Mud rash” or “mud fever.” • Caused by 
Dermatophilus congolensis . • Rare crusting 
dermatitis (dogs). • Rare nodular subcutaneous 
and oral disease (cats). • Systems affected—
skin/exocrine.
• Dogs and cats. • No age, breed, or sex 
SIGNS
• Association with cattle, sheep, or horses. 
• Occasionally free-roaming dogs. • Cats with 
subcutaneous disease—  episode of trauma; 
existence of a foreign body; lesions generally 
chronic; no systemic clinical signs, except when 
internal organs or large oral lesions develop.
• Dogs—lesions: circular to coalescent, papular, 
crusted skin lesions on the head and/or trunk, 
lesions resemble superficial bacterial pyoderma 
caused by Staphylococcus pseudintermedius ; 
lesions may resemble dermatophilosis in horses 
(adherent thick, gray-yellow crusts that 
incorporate hair and leave a circular, glistening, 
shallow erosion when removed); pruritus is 
variable. • Cats—subcutaneous, oral, or internal 
ulcerated and fistulated nodules or abscesses 
similar to lesions caused by other actinomycetes 
in this species; superficial pyogenic crusting 
disease of the face has been reported.
• D. congolensis —causative agent; Gram-positive, 
branching filamentous bacterium classified as an 
actinomycete; very common cause of crusting 
dermatoses in hoofed animals; persists in the 
environment within crusts. • Dogs, cats, and 
humans can be exposed directly from lesions 
on large animals or from environmental 
exposure. • Infectious stage—requires wetting 
for activation; cannot penetrate intact 
epithelium; minor trauma or mechanical 
transmission by biting ectoparasites ( Amblyomma 
variegatum ) may help in establishing infection. 
• Deeper infections—require traumatic 
inoculation of infectious material.
  DIAGNOSIS
Dogs
• Staphylococcal folliculitis. • Acute moist 
dermatitis. • Dermatophytosis. • Pemphigus 
foliaceus. • Keratinization disorder.Cats
• Infections—actinomycosis, nocardiosis, 
sporotrichosis, cryptococcosis, opportunistic 
mycobacterial granuloma, Rhodococcus 
equi.• Foreign body. • Bite wound abscess.
• Cutaneous or mucosal neoplasia.
Dogs
• Cytologic examination of exudate from 
under crusts or of macerated crusts. 
• Biopsy—crusts contain organisms; submit 
with tissue samples. • Distinctive morphol-
ogy of organism in cytologic and histopatho-
logic preparations; bacterium forms branching 
chains of small diplococci resembling “railroad 
tracks.” • Real-time quantitative polymerase 
chain reaction (RT-qPCR)—crust samples 
and hair.
Cats
• Histopathologic examination—biopsy of 
nodules; procedure of choice. • Culture from 
crusts or tissues—alert laboratory of differential; 
requires use of special selective medium; 
isolation is possible but usually very difficult. 
• RT-qPCR—crust samples and hair.
• Dogs—crusting and superficial pustular 
dermatitis; palisading of the crusts with 
orthokeratotic and parakeratotic hyper -
keratosis; organism visualized within the 
crusts. • Cats—pyogranulomatous 
inflammation; central necrosis; fistulous 
tract formation; organism visualized near 
the necrotic center of granulomas, 
especially with Gram stain.
  TREATMENT
• Dogs—antibacterial shampoo with gentle 
removal of crusts: iodine or lime-sulfur may 
also be used. • Cats—for pyogranulomas 
and abscesses: surgical debridement; 
exploration for foreign body; establishment 
of drainage for exudate.
• T reatment should be continued for 10–20 
days. • Penicillin V (10 mg/kg PO q12h) for 
10–20 days; drug of choice. • Tetracycline 
(22–30 mg/kg PO q8h); doxycycline 
(5–10 mg/kg PO q12h); minocycline 
(5–12 mg/kg PO q12h. • Ampicillin 10–20 mg/kg PO q12h. • Amoxicillin 
10–20 mg/kg PO q12h.
  FOLLOW-UP
• Dogs—reexamine after 2 weeks of treat-  
ment to ensure complete resolution; give an 
additional 7 days of systemic therapy if 
indicated. • Cats—monitor biweekly for 1 
month after apparent resolution of lesions, 
depending on location.
• Dogs—excellent. • Cats—varies with the 
location of lesions and extent of surgical 
debridement; complete resolution can be 
achieved with early diagnosis and medical/
surgical therapy.
• Veterinarians and animal care workers—
infection uncommon even with exposure to 
infected farm animals.
• Dogs and cats—very unlikely to serve as a 
source for human infection; caution is 
warranted for exposure of immunocompro-
mised individuals.
• RT-qPCR = real-time quantitative 
polymerase chain reaction.
Frank LA, Kania SA, Weyant E. RT-qPCR 
for the diagnosis of dermatophilosis in 
horses. Vet Dermatol 2016, 
27(5):431–e112.
Hirazumi M, Tagawa Y. Isolation and 
characterization of flagellar filament from 
zoospores of Dermatophilus congolensis. 
Vet Microbiol 2014, 173(1–2):141–146.
Author  Mitchell D. Song
Resnick

370  Blackwell’s Five-Minute Veterinary Consult  
DDermatophytosis
  BASICS
• Cutaneous fungal infection affecting the 
cornified regions of hair, claws, and occasion-
ally the superficial layers of the skin.
• Microsporum  and Trichophyton  dermato-
phytes are most commonly isolated.
• Dermatophytes—grow in the keratinized 
layers of hair, claw, and skin; do not thrive in 
living tissue.
• Exposure to or contact with a dermato-
phyte does not necessarily result in an 
infection. Infection may not result in clinical 
signs.
• 2–4-week incubation period.
• Infective spores must contact the skin 
surface and defeat host-protective mecha-
nisms (innate immunity, normal flora, sebum, 
grooming) in order for infection to occur.
• Factors that favor the development of 
disease—stress, trauma, ectoparasite infest  - 
ations, and immunosuppression.
• Infected animals may remain as asympto-
matic (inapparent) carriers for a prolonged 
period of time; some animals never become 
symptomatic.
• Lesions may mimic many dermatologic 
conditions; overdiagnosis is likely common.
• Infection rates (inapparent and clinical) vary 
widely, depending on the population studied.
• More common in hot, humid climates.
• Incidence of dermatophyte species may vary 
seasonally and geographically.
• M. canis —cats: UK, southern United 
States, Italy, and Brazil; source most often 
infected cat.
• M. gypseum —dogs: southern United States; 
less than 1% in UK; source most often soil.
• M. persicolor —India, Brazil, and North 
America; source most often associated with 
rodents.
• T. mentagrophytes —India and UK; less common 
in southern United States, Italy, and Brazil; source 
most often associated with rodents.
Species
Dog, cat, and many others.
• Cat—longhaired breeds (Persian and 
• Dog—Yorkshire terrier and Manchester 
terrier. Increased exposure in working and 
hunting dogs.Mean Age and Range
• M. canis  is more common in younger animals.
• Generalized dermatophytosis in older dogs 
associated with immunosuppression.
SIGNS
• Inapparent carrier state—cats.
• Extreme variability of clinical signs.
• Classic lesion—slowly expanding circular 
patch of alopecia with scale.
• Seborrheic or greasy hair coat.
• Papular or pustular eruptions.
CAUSES
Multiple species identified; majority of 
cases caused by M. canis , M. gypseum , 
T. mentagrophytes , and M. persicolor  
(nonfollicular).
• Immunocompromise caused by medica-
tions or disease.
• High population density.
• Poor management practices.
  DIAGNOSIS
• Staphylococcal folliculitis.
• Allergic dermatitis.
• Pemphigus foliaceus.
• Keratinization defect.
Wood’s Lamp Examination
• Can be misleading—not all M. canis  
isolates fluoresce ; most other pathogenic 
dermatophytes do not fluoresce.
• T rue positive reaction—apple-green 
fluorescence of the hair shaft. False-positive 
and false-negative results commonly due to 
debris on the hair and skin, inadequate 
equipment, and/or poor technique.
Microscopic Examination of Hair
• Choose hairs that fluoresce under Wood’s 
lamp illumination to increase success.
• Hyphae and arthrospores seen invading hair 
shafts.
Fungal Culture with Identification
lamp if possible.
• Pluck hairs from the periphery of an 
alopecic area or brush haircoat with a sterile 
toothbrush or carpet square (especially 
inapparent or treated patients).
• Dermatophyte test media—dermatophytes 
change media color to red during the early 
growing phase of the culture; saprophytes 
cause color change after significant colony 
growth; examine inoculated media daily.
• Fungal colonies are nonpigmented/white to 
slightly yellow. Contaminants are often darker.• Microscopic examination of the growth for 
microconidia and macroconidia—necessary 
to confirm pathogenic dermatophyte and to 
identify genus and species; helps identify 
source of infection.
• Positive culture—indicates presence of a 
dermatophyte; however, organisms may be 
transient (i.e., geophilic dermatophytes on 
the feet).
• Not usually required for diagnosis.
• Can be helpful in confirming true invasion 
and infection, or to diagnose suspicious cases 
with negative fungal culture.
PCR
PCR of the dermatophyte DNA on the hair 
samples may be helpful. Positive PCR does 
not necessarily indicate active infection—
dead fungal organisms from a successfully 
treated infection may be detected on PCR, as 
will inapparent carriers.
• Folliculitis, perifolliculitis, or furunculosis.
• Fungal hyphae seen in H&E-stained 
sections; special stains allow easier visualiza-
tion of the organism.
  TREATMENT
Quarantine owing to the infective and 
zoonotic nature of the disease.
• Many shorthaired cats and many dogs will 
undergo spontaneous remission within 3 
months.
• Longhaired animals should be clipped to 
reduce environmental contamination.
• Decontamination of the environment 
reduces the risk of false positive fungal 
cultures, which can lead to prolonged 
treatment and confinement.
• Infective spores are shed into the environ -
ment, but do not multiply in the environ -
ment; transmission of the disease strictly 
from a contaminated environment (i.e., no 
direct contact with an infected animal) is 
extremely rare.
• Effective disinfectants.
• Diluted sodium hypochlorite (0.5%)— 
concentrations ranging from 1 : 10 to 1 : 100 
effective with short contact times.
• Enilconazole (0.2%)—available as a 
concentrated spray or fogger; 10-minute 
contact time recommended. Not available in 
the United States.
• Accelerated hydrogen peroxide—should not 
be mixed with concentrated sodium hypo  - 
chlorite products; 10-minute contact time 
• Washable textiles—decontaminate via 
mechanical washing; two washings on the

Canine and Feline, Seventh Edition  371
Dlongest wash cycle in a washing machine 
found to be effective.
• T reatment can be both frustrating and 
expensive, especially in multianimal house  - 
holds or with recurrent cases; consider referral 
to a veterinary dermatologist.
• Topical therapy and clipping— recom-
mended concurrently with systemic therapy; 
may help prevent environmental contam  - 
ination.
• Lime-sulfur (1 : 16 dilution or 8 oz per 
gallon of water), miconazole/chlorhexidine 
(0.2%), or enilconazole (0.2%) applied once 
to twice weekly; lime sulfur is odoriferous 
and can stain; enilconazole is not currently 
approved for use in companion animals in 
the United States. Shampoos containing 
1–2% ketoconazole, miconazole, or 0.5% 
climbazole; a minimum of a 3-minute 
contact time is recommended; little to no 
residual effect.
• Use of an Elizabethan collar, particularly in 
cats, is recommended to prevent ingestion of 
these products.
• Itraconazole—dogs and cats: 5–10 mg/kg 
PO q24h in one-week-on, one-week-off 
schedule for minimum of 3 cycles; manufac-
tured drug preferred over compounded 
formulations due to absorption/concentration 
variability. Compounded formulations have 
been shown to be of extremely variable 
efficacy.
• Ketoconazole—resistance reported (10 mg/
kg q24h PO); not recommended in cats.
• Griseofulvin—effective, but use declining 
due to cost and requirement for monitoring.
• Terbinafine—effective, may be helpful in 
cases resistant to azole drugs; dogs: 
20–30 mg/kg q12–24h for 4–8 weeks; cats: 
20–40 mg/kg q24–48h for 4–8 weeks; 
dermatophyte carriers: 8.25 mg/kg q24h for 
4–8 weeks; side effects may include gastroin-
testinal upset, hepatotoxicity, neutropenia, 
and pancytopenia.
• Antifungal vaccines have not been shown to 
protect against challenge exposure.
• Corticosteroids—can modulate inflamma-
tion and prolong the infection.
• Griseofulvin—do not administer to cats 
with feline leukemia virus (FeLV) or feline 
immunodeficiency virus (FIV); teratogen.PRECAUTIONS
Ketoconazole
• Hepatopathy has been reported and can be 
severe in cats.
• Inhibits endogenous production of steroid 
hormones in dogs.
• Rare vasculitis and ulcerative skin lesions at 
doses of 5 mg/kg q12h; not noted in patients 
receiving 5 mg/kg q24h.
• Hepatotoxicity reported infrequently in 
dogs.
Terbinafine
• Gastrointestinal upset, hepatotoxicity, and bone 
marrow suppression (pancytopenia, neutropenia).
• Decrease dosage with renal and/or hepatic 
• Concurrent administration with Cimetidine  
increases blood concentration; rifampin 
decreases blood concentration.
Lime-Sulfur Solution
Ingestion of lime-sulfur may lead to oral 
erosions.
• Lufenuron—a chitin synthesis inhibitor 
used in flea control; not effective in con-
trolled studies.
• Fluconazole—less effective option, but less 
expensive than itraconazole.
  FOLLOW-UP
• Dermatophyte culture required to monitor 
response to therapy; many animals clinically 
improve but remain culture-positive.
• Continue treatment until at least two 
subsequent cultures are negative.
• In resistant cases, cultures should be repeated 
weekly using the toothbrush technique.
• Weekly or biweekly CBC if treating with 
griseofulvin; periodic evaluation of liver 
enzymes if treating with ketoconazole, 
itraconazole, or terbinafine.
• Depending on which systemic medications 
used, appropriate follow-up should be 
performed due to potential side effects.
• Initiate a quarantine period and obtain 
dermatophyte cultures of all animals entering 
the household to prevent reinfection from 
inapparent carriers.
• Consider exposure based on species 
isolated.• Decontaminate the environment.
• Consider prophylactic treatment of exposed 
animals.
False-negative dermatophyte culture.
• Many animals will “self-clear” infection 
over a period of a few months.
• T reatment hastens clinical cure and helps 
• Some infections, particularly in longhaired 
cats or multianimal situations, can be 
persistent.
• Dermatophytosis is zoonotic.
• Considered a low-level pathogen; disease is 
not life-threatening, can be easily treated, but 
may cause scarring.
BREEDING
• Griseofulvin is teratogenic.
• Ketoconazole can affect steroidal hormone 
synthesis, especially testosterone.
SYNONYMS
Ringworm
Bond R. Superficial veterinary mycoses. Clin 
Dermatol 2010, 28(2):226–236. doi: 
10.1016/j.clindermatol.2009.12.012
7th ed. Philadelphia, PA: Saunders, 2013, 
pp. 5226–5241.
B. Diagnosis and treatment of dermatophy-
tosis in dogs and cats. Vet Dermatol 2017, 
28(3). doi: 10.1111/vde.12440
Authors  W. Dunbar Gram and Andhika 
Putra
Resnick
editors acknowledge the previous contribu-
tion of Sheena Narine-Reece
available online(continued)  Dermatophytosis

372  Blackwell’s Five-Minute Veterinary Consult  
DDermatoses, Depigmenting Disorders
  BASICS
• Pathologic or cosmetic condition involving 
loss of pigmentation of the skin and/or hair 
coat, either by lack of pigmentation or by 
melanocyte damage.  • Leukotrichia—whiten-
ing of the hair (nonspecific location).  • Poliosis 
—whitening of hair on the head/face. 
• Leukoderma—whitening of the skin.
• Melanocytes may be damaged or destroyed 
by toxins (including toxic melanin precursors), 
inflammatory mediators, auto-antibodies, and/ 
or inhibitors of melanogenesis. • Diseases 
may be distinguished clinically by depigmen-
tation as the initial symptom versus depig-
mentation occurring secondary to inflamm- 
ation.
• Skin/exocrine. • Ophthalmic.
• Mucocutaneous pyoderma—German 
shepherd dog.  • Systemic lupus erythemato-
sus (SLE)—German shepherd dog.  • Discoid 
lupus erythematosus (DLE)—collie, Shetland 
sheepdog, German shepherd dog, Siberian husky; 
may occur more often in females.  • Pemphigus 
foliaceus (PF)—chow chow, Akita, cocker 
spaniel, dachshund, Labrador retriever.  
• Uveodermatologic syndrome—Akita, 
Samoyed, Siberian husky.  • Vitiligo—dogs: 
Belgian Tervuren, German shepherd dog, 
Doberman pinscher, Rottweiler, German 
shorthaired pointer, Old English sheepdog, 
dachshund; usually less than 3 years of age; 
cats: Siamese.  • Seasonal nasal hypopigmenta -
tion—Siberian husky, Alaskan Malamute, 
Labrador retriever, golden retriever.
• Epitheliotropic lymphoma (mycosis 
fungoides)—typically dogs >10 years old.  
• Proliferative arteritis of the nasal philtrum—  
Saint Bernard, giant schnauzer.  • Periocular 
leukotrichia—Siamese cat. •  Chediak-
Higashi syndrome—Persian cat.
SIGNS
• Leukotrichia. • Leukoderma.  • Lightening 
of the pigmentation in the skin (seen as a 
“graying” or “browning” of previously 
pigmented areas).  • Erythema.  • Erosion and 
ulcerations.
CAUSES
• Mucocutaneous pyoderma.  • DLE.  • SLE.  
• P F. • Pemphigus erythematosus (PE).  
• Uveodermatologic syndrome.  • Contact 
hypersensitivity. • Vitiligo.  • Seasonal nasal 
depigmentation.  • Albinism.  • Schnauzer 
gilding syndrome.  • Endocrinopathy.  • Drug 
reaction.  • Erythema multiforme (EM).  
• Proliferative arteritis of the nasal philtrum.  
• Postinflammatory depigmentation.  • Immune-mediated pigmentary inconti-
nence.  • Oculocutaneous albinism.
• Sun exposure—DLE, SLE, and PE.  • Drug 
triggered—PF , EM.
  DIAGNOSIS
Mucocutaneous Pyoderma
• Biopsy—epidermal hyperplasia with 
superficial pustulation. • Depigmentation is 
secondary and develops with chronicity.  
• Skin lesions—affects the lips, perioral area, 
and nasal/alar folds.  • Clinically similar to 
intertrigo (skinfold bacterial folliculitis).  
• Swelling and fissuring lead to erosions and 
crusts.  • ++Biopsy—epidermal hyperplasia 
with superficial pustulation.  • Antibiotic 
responsive.  • Frequent recurrence if due to an 
Nasal Solar Dermatitis
• Depigmentation is secondary and develops 
with chronicity.  • Lesions confined primarily to 
dorsal muzzle and precipitated by sun exposure.  
• Begins in poorly pigmented skin at the junction 
of the nasal planum and dorsal muzzle.  • Negative 
for direct immunofluorescence.  • Solar vasculo-  
pathy may appear similar.
DLE
• Depigmentation is a primary symptom.  
• Primarily affects nasal area, eyelid margins, 
and lip margins.  • Exacerbated by sun 
exposure.  • Positive direct immunofluores-
cence at basement membrane zone.  
• Biopsy—interface dermatitis.
SLE
• Multisystemic disease.  • Skin lesions—
often involve nose, face, and mucocutaneous 
junctions; multifocal or generalized.  
• Antinuclear antibody (ANA)—may be 
positive.  • Positive direct immunofluores-
cence at basement membrane zone.
PF
• Depigmentation develops with chronicity.  
• Initial lesions on face and ears; commonly 
involve footpads; eventually generalized.  
• Biopsy—subcorneal pustules with acantholysis.  
• Positive direct immunofluorescence in 
intercellular spaces of epidermis.
PE
• Lesions—primarily confined to face and 
ears, nasal planum, and lip margins.  
• Depigmentation often precedes significant 
lesions.  • Exacerbated by sun exposure.  
• Biopsy—intraepidermal pustules with 
acantholysis and interface dermatitis.  
• Positive direct immunofluorescence at basement membrane zone and intercellular 
spaces.  • ANA—occasionally positive.
Uveodermatologic Syndrome
• Uveitis—usually precedes dermatologic 
disease.  • Cutaneous macular depigmentation 
with inflammation on nose, lips, and eyelids.  
• Striking poliosis and leukotrichia.  • Biopsy 
of early lesions—interface dermatitis, 
pigmentary incontinence.
Others
• Contact dermatitis (uncommon)—depig -
mentation secondary due to chronicity; 
erythema of rostral nasal planum and lips; no 
ulceration and minimal crusting; history of 
exposure.  • Vitiligo—depigmentation often 
without inflammation; cutaneous macular 
depigmentation on nose, lips, eyelids, 
footpads, and nails; concurrent leukotrichia.  
• Seasonal nasal hypopigmentation—depigmenta -
tion is a primary symptom; normal black 
coloration of nasal planum fades to light tan or 
pink; usually seasonal or slowly progressive with 
age. • Albinism—hereditary lack of pigment 
of the skin, hair coat, and irises (not a 
depigmenting process).  • Aurotrichia—
young miniature gray schnauzers may 
develop idiopathic golden hair coat 
coloration, primarily of the trunk.  
• Endocrinopathy may cause coat color 
change, mainly from black to reddish-
brown.  • Drug reaction—depigmentation is 
often secondary; resembles many cutaneous 
disorders such as DLE, SLE, PF , and PE; 
pruritus is variable; onset of symptoms is 
usually within 2 weeks of administration.  
depigmentation is secondary and develops 
with chronicity; marked focal ulceration of 
the nasal planum often resulting in acute, 
severe hemorrhage; no additional skin 
lesions noted; this may be an idiopathic 
syndrome associated with allergy.  
• Dermatophytosis— depigmentation is 
secondary and develops with chronicity; 
especially develops on the dorsal muzzle 
and face; hyperpigmentation may also 
occur, especially with Tricophyton mentagro -
phytes  infection.  • Epitheliotropic lym -
phoma—depigmentation is secondary and 
develops with chronicity; occurs in 
mucocutaneous areas, nose, and skin.  • EM 
in dogs—classic annular lesions with a clear 
center; depigmentation is secondary and 
develops with chronicity.  • Zinc defi -
ciency—depigmentation may be a primary 
or secondary symptom; zinc is required for 
normal melanin synthesis.  • Chediak-
Higashi syndrome—depigmentation is a 
primary symptom; young Persian cats (blue 
smoke color); ophthalmologic signs, 
prolonged bleeding.  • Cyclic neutropenia 
in young silver-gray collie dogs with 
light-colored nose.

Canine and Feline, Seventh Edition  373
DCBC/BIOCHEMISTRY/URINALYSIS
• Usually normal.  • SLE—may see hemolytic 
anemia, thrombocytopenia, or evidence of 
glomerulonephritis.  • Hematologic abnor-
malities in Persian cats with Chediak-Higashi 
syndrome.  • Cyclic neutropenia in collie dogs 
(cyclic hematopoiesis anomalies).
• Fungal culture—dermatophytosis.  
• ANA—positive in SLE.
• Cytology—acantholytic cells (pemphi -
gus), neoplastic lymphocytes (epithelio -
tropic lymphoma).  • Joint tap—evidence of 
polyarthritis in SLE.  • Ocular examina -
tion—uveitis in uveodermatologic syn -
drome.  • Direct immunofluorescence—  
deposition of immunoglobulin at the 
basement membrane zone with DLE, SLE, 
and PE, and in the intercellular spaces of 
the epidermis with PF and PE.  • Skin 
biopsy.  • Genetic testing for oculocutaneous 
albinism.
Histopathologic Examination of the Skin
• Interface dermatitis—DLE, SLE, uveoder-
matologic syndrome.  • Pigmentary inconti-
nence—DLE, PE.  • Intraepidermal 
pustules with acantholysis—PF and PE.  
• Hypomelanosis—vitiligo, uveodermato-
logic syndrome, seasonal nasal hypopigmenta -
tion, and Auriotrichosis.  • Apoptosis 
(individual cell necrosis of keratinocytes)—
drug reaction and EM.  • Proliferation of 
spindle cells of dermal arteries and arteri -
oles—proliferative arteritis.  • Infiltration of 
neoplastic lymphocytes— epitheliotropic 
lymphoma.
  TREATMENT
• Outpatient, except for SLE, EM, and 
cutaneous lymphoma with systemic involve-
ment.  • Reduce exposure to sunlight—DLE, 
SLE, and PE.  • Immunosuppressive therapy—
SLE, PF , and PE.  • Avoid contact with topical 
drugs.  • Contact dermatitis—avoid irritant; 
replace plastic or rubber dishes: particularly if roughened edges cause abrasions.  
• Application of water-resistant sunblock 
ointments or gels with an SPF/UVA and 
UVB >30 to depigmented and sun-exposed 
areas of skin.  • Uveodermatologic syn-
drome—management by veterinary ophthal-
mologist recommended.  • Appropriate 
antibiotics—pyoderma.  • Appropriate 
antifungals— dermatophytosis.
• Auto-immune dermatoses—immuno -
suppressive therapy with prednisolone or 
dexamethasone and azathioprine (dogs) or 
chlorambucil (cats); see specific diseases.  
• Topical corticosteroids—PE, DLE.  
• Vitiligo and nasal depigmentation—no 
treatment.  • Epitheliotropic lymphoma—
multiple treatment protocols.
Azathioprine therapy—not recommended in 
cats; may cause fatal leukopenia or 
thrombocytopenia.
ADVERSE REACTIONS
Ketoconazole may cause lightening of the hair 
coat, elevated alkaline phosphatase, and gastro  - 
intestinal distress.
• Cyclosporine, modified—5 mg/kg/day for 
auto-immune disorders.  • Tacrolimus—0.1% 
gel applied daily to lesions in combination 
with or to replace corticosteroids; may sting; 
avoid licking; wear latex gloves to apply.  
• Pimecrolimus—1% cream applied daily to 
lesions in combination with or to replace 
corticosteroids; may sting; avoid licking; wear 
latex gloves to apply.
  FOLLOW-UP
• Varies with specific disease and treatment 
prescribed.  • Postinflammatory depigmentation 
should resolve when the cause of inflamma-
tion is treated.POSSIBLE COMPLICATIONS
• Sunburn in areas of depigmentation.  
• Squamous cell carcinoma—in cases of solar 
damage and actinic keratosis of depigmented 
areas.  • SLE—associated scarring with 
ulcerative dermatitis.
Dermatophytosis—can cause infection in 
humans.
SEE ALSO
• Cutaneous Drug Eruptions.
• Lupus Erythematosus, Cutaneous (Discoid).
• DLE = discoid  lupus erythematosus.
• PE = pemphigus erythematosus.
• PF = pemphigus foliaceus.
Mealey KL. Pharmacotherapeutics for 
Veterinary Dispensing. Ames, IA: Wiley-
Blackwell, 2019.
Miller W, Griffin C, Campbell, K. Muller 
and Kirk’s Small Animal Dermatology, 7th 
ed. St. Louis, MO: Elsevier, 2013.
Morris DO, Kennis RA. Clinical dermatol-
ogy, special issue. Vet Clin Small Anim 
Pract 2013, 43(1).
Torres SMF , Roudebush P , eds., Advances in 
Veterinary Dermatology, Vol. 8. Hoboken, 
NJ: Wiley, 2017.
Resnick
available online(continued)  Dermatoses, Depigmenting Disorders

374  Blackwell’s Five-Minute Veterinary Consult  
DDermatoses, Erosive or Ulcerative
  BASICS
A heterogenous group of skin disorders 
characterized by disruption of the epidermis 
(erosions) or, if the basement membrane is 
compromised, the epidermis and dermis (ulcers).
Varies widely, depending on the cause; may 
include congenital or developmental 
disorders that compromise tissue cohesion; 
cell-mediated (inflammatory or neoplastic) 
injury; anoxic injury; antigen-specific 
auto-immune disorders; and necrosis due to 
trauma, toxins, contactants (irritants), 
microbial organisms, or parasitic migration.
GENETICS
Some diseases are likely heritable due to breed 
predilections; however, there are no genetic 
screening tests available for any of the diseases 
listed.
Rare to common, depending on the cause.
Species
Some specific causes (see below) have strong breed 
predilections, e.g., lupoid disorders, familial 
dermatomyositis, and zinc-responsive dermatosis.
• Highly variable according to etiology. 
• Canine juvenile cellulitis and several 
congenital diseases (see below) are diagnosed 
in very young animals.
Sex predispositions may vary according to 
the disease in question.
SIGNS
• Pruritus may result in ulcers or erosions 
due to self-trauma; especially ectoparasitism, 
superficial pyoderma, and Malassezia  
dermatitis. •  Exposure to caustic chemicals, 
burns, cold stress, venomous reptiles and 
insects, etc. •  Some infectious diseases (e.g., 
pythiosis, coccidioidomycosis, feline cow 
pox) have very restricted ranges. • Previous 
or concurrent systemic signs or illness.
• Lesions may be heterogenous in gross 
appearance; some diseases result in erythematous 
erosions with minimal crust or scale, while others 
cause scale or crusting that (when removed) 
results in erosion. •  Ulcers may be shallow/superficial or deep; deep ulceration can present as 
sinuses with draining tracts, cavitated lesions with 
well-demarcated borders, or exudative crusted 
lesions. •  Some specific diseases are typically 
accompanied by fever and malaise, especially 
auto-immune disorders and infectious etiologies. 
• May be associated with extracutaneous disease 
(e.g., superficial necrolytic dermatitis and hyper  - 
eosinophilic syndrome of cats).
CAUSES
• Pemphigus foliaceus—crusting with erosion. 
• Pemphigus vulgaris—superficial ulcerative. 
• Bullous pemphigoid and epidermolysis 
bullosa acquisita—superficial ulcerative. 
• Discoid lupus erythematosus and muco -
cutaneous lupus erythematosus—erosive or 
superficial ulcerative. •  Exfoliative lupus 
(German shorthaired pointers)—scaling 
with erosion. • Vesicular lupus (rough collies 
and Shetland sheepdogs)—superficial 
ulcerative. • Cold agglutinin disease—deep 
ulcerative.
• Erythema multiforme, Stevens–Johnson 
syndrome, and toxic epidermal necrolysis (may 
be drug induced)—erosive to superficial 
ulcerative. •  Vasculitis—superficial to deep 
ulcerative (may be cavitated). •  Idiopathic 
panniculitis—deep ulcerative (usually exudative 
with crusting). •  Canine eosinophilic furunculo -
sis of the face (may be insect related)—ulcerative 
and crusting. •  Canine juvenile cellulitis (puppy 
strangles)—erosive to superficial or deep 
ulcerative. •  Feline indolent ulcer (rodent 
ulcer)—erosive to superficial or deep ulcerative.
• Surface pyoderma—acute moist pyotrau -
matic dermatitis: erosive. •  Superficial 
staphylococcal folliculitis—erosive to 
superficial ulcerative. •  Bacterial folliculi -
tis/furunculosis—deep ulcerative. 
• Superficial fungal ( Malassezia  dermatitis, 
dermatophytosis)—erosive to superficial 
ulcerative. •  Deep fungal (sporotrichosis, 
cryptococcosis, histoplasmosis, blastomyco -
sis, coccidioidomycosis)—deep ulcerative 
with or without sinuses and draining tracts. 
• Opportunistic mycobacteriosis—deep 
ulcerative nodules with sinuses and draining 
tracts. • Actinomycetic bacteria ( Nocardia  
spp., Actinomyces  spp., Streptomyces  
spp.)—deep ulcerative nodules with sinuses 
and draining tracts. •  Pythiosis/lagenidiosis 
and protothecosis— ulcerative, prolifera -
tive with or without draining tracts. 
• Leishmaniasis—erosive to superficial or 
deep ulcerative. • Feline cow pox—deep 
ulcerative. •  Feline immunodeficiency 
virus (FIV)/feline leukemia virus (FeLV) 
related—erosive to superficial ulcerative. 
• Feline herpesvirus-associated dermato -
sis—ulcerative with crusting.Parasitic
• Demodicosis—ulcerative with crusting 
(especially with secondary bacterial folliculi-
tis). •  Sarcoptic/notoedric mange—erosive 
with crusting. •  Flea bite allergy—erosive to 
ulcerative. •  Feline mosquito bite hypersensi-
tivity—erosive to superficial or deep ulcerative. 
• Pelodera  and hookworm migration—deep 
Congenital/Hereditary
• Canine familial dermatomyositis (predomi -
nantly in collies and Shetland sheepdogs)—
erosive. •  Epidermolysis bullosa—superficial 
ulcerative. • Cutaneous asthenia (Ehlers–
Danlos syndrome)—skin tears easily.
Metabolic
• Superficial necrolytic dermatitis (usually 
associated with advanced hepatic disease or 
pancreatic glucagonoma)—crusting with 
erosion. •  Hyperadrenocorticism—erosive to 
ulcerative when complicated by secondary 
infections or calcinosis cutis. •  Uremia 
(mucous membranes)—superficial ulcerative.
• Squamous cell carcinoma—erosive to 
ulcerative with scale or crust. •  Feline 
squamous cell carcinoma in situ (Bowenoid 
in situ carcinoma)—erosive with scale or 
crust. •  Mast cell tumors—superficial to 
deep ulcerative. •  Epitheliotropic lymphoma 
(mycosis fungoides)—erosive to superficial 
ulcerative. • Feline thymoma-associated 
exfoliative dermatosis—scaling with erosion. 
• Feline paraneoplastic alopecia—erosive.
Nutritional
Zinc-responsive dermatosis—crusting with 
erosion.
Physical/Conformational  
Dermatoses
• Pressure point ulcers—deep ulcerative. 
• Intertrigo (skinfold pyoderma)—erosive.
• Feline dorsal neck ulcer—deep ulcerative 
with crusting. •  Canine and feline acne—
erosive to ulcerative. •  Feline plasma cell 
pododermatitis—superficial to deep 
Thermal (heat/cold), electrical, solar, or 
chemical irritant/burns—depth of lesions 
depends on severity of insult.
  DIAGNOSIS
Depends upon presentation.
May be abnormal with metabolic or systemic 
disease.

Canine and Feline, Seventh Edition  375
DIMAGING
• Rarely indicated. •  Thoracic radio -
graphs—deep/systemic fungal diseases, 
feline thymoma-associated exfoliative 
dermatitis, or systemic neoplasia. 
• Abdominal ultrasound—superficial 
necrolytic dermatitis (dogs) or paraneoplas -
tic alopecia (cats).
• Skin scraping—ectoparasitism. •  Direct 
impression cytology—bacteria, yeast, or 
acantholytic keratinocytes in pemphigus. 
• Fine-needle aspirate with cytology— indu -
rated or nodular lesions. •  Culture: bacterial 
(aerobic and anaerobic), mycobacterial, and/or 
fungal—suspected infectious disease. •  Fungal 
serology and serology for pythiosis and 
lagenidiosis may be indicated on a case-by-
case basis and depending upon geographic 
location. •  PCR and immunohistochemistry 
are adjuncts to the histologic diagnosis of 
feline herpesvirus-associated dermatitis.
• For cavitated lesions, the leading edge 
(elliptical full-thickness biopsy) should be 
harvested with a scalpel blade if the defect is 
too large to be excised in total. •  Punch biopsy 
sufficient for diffuse erosive lesions; should 
take normal skin near a lesion and lesions that 
are both early and late in development.
  TREATMENT
• Outpatient for most diseases. •  Varies 
widely according to the cause.
DIET
• Nutritional support may be necessary in 
debilitated animals, especially those with 
superficial necrolytic dermatitis. •  Correcting 
dietary deficiencies is the only treatment for 
generic dog-food dermatosis. •  Supple- 
mentation of zinc is necessary for zinc-
responsive dermatosis.
Variable by diagnosis; most important with 
suspected or confirmed zoonotic disease.
• Indicated as curative treatment for feline 
thymoma-associated exfoliative dermatitis. 
• May be curative for nonmetastatic 
pancreatic or hepatobiliary tumors causing 
paraneoplastic alopecia. •  Radical surgical 
excision of nodules and draining tracts may 
be an adjunct to antimicrobial therapy of 
infections caused by rapid-growing 
Mycobacteria  spp. and Nocardia  spp. in cats 
and pythiosis or lagenidiosis in dogs.  MEDICATIONS
Variable by cause.
Side effects—associated with many antimicrobial, 
immunosuppressive, and antineoplastic drugs.
Dependent on medications administered.
  FOLLOW-UP
Dependent on disease process, concurrent 
systemic disease(s), drugs used, and potential 
side effects expected.
• Incidence of many feline infectious diseases 
can be minimized by restricting outdoor 
activity. •  Some autoimmune diseases (lupus 
and pemphigus) are aggravated by ultraviolet 
light exposure; patients should be restricted 
from sun exposure during peak hours of the day.
• Determined by cause. •  Some diseases are 
potentially life-threatening. •  Some diseases 
have zoonotic potential. •  Infections and 
drug side effects are possible in cases requiring 
• Some infectious diseases (nocardiosis, atypical 
mycobacteriosis) may be controlled with chronic 
antimicrobial therapy, but are generally not 
curable if lesion progression is extensive by the 
time of diagnosis. •  Pythiosis/lagenidiosis—
prognosis is extremely poor for response to 
therapy and survival when lesions are extensive.
• Sarcoptic acariasis. •  Dermatophytosis. 
• Sporotrichosis. •  Mycelial phase of some 
fungi (e.g., Coccidioides immitis , Blastomyces 
dermatitidis ), when grown on culture media, 
can be infectious to humans through 
inhalation. In-clinic fungal culturing (other 
than for dermatophytes) is not advised.
• Due to the potential severity of clinical 
signs and syndromes, any patient diagnosed 
with an erosive/ulcerative disease that occurs 
with moderate to strong breed predilections 
should not be used for breeding. •  Many 
drugs used to treat the auto-immune, immune-mediated, and infectious diseases 
listed may be teratogens.
SYNONYMS
Superficial necrolytic dermatitis = necrolytic 
migratory erythema, metabolic epidermal 
necrosis, hepatocutaneous syndrome.
SEE ALSO
• Acne—Cats.
• Acne—Dogs.
• Actinomycosis & Nocardia.
• Blastomycosis.
• Coccidioidomycosis.
• Cold Agglutinin Disease. 
• Cryptococcosis. 
• Demodicosis. 
• Dermatophytosis. 
• Feline Herpesvirus Infection. 
• Feline Immunodeficiency Virus (FIV) 
Infection. 
• Feline Paraneoplastic Alopecia. 
• Histoplasmosis. 
• Hyperadrenocorticism (Cushing’s Syndrome—  
Dogs. 
Cats. 
• Leishmaniosis, Cutaneous. 
• Lupus Erythematosus, Cutaneous (Discoid). 
• Lymphoma, Cutaneous Epitheliotropic. 
• Malassezia Dermatitis. 
• Mast Cell T umors. 
• Mycobacterial Infections. 
• Notoedric Mange. 
• Panniculitis/Steatitis. 
• Pemphigus. 
• Pododermatitis. 
• Protothecosis. 
• Puppy Strangles (Juvenile Cellulitis). 
• Pyoderma. 
• Pythiosis. 
• Sarcoptic Mange. 
• Sporotrichosis. 
• Squamous Cell Carcinoma, Skin. 
• Superficial Necrolytic Dermatitis. 
• Vasculitis, Cutaneous.
Mason IS. Erosions and ulcerations. In: 
Ettinger SH, Feldman EC, eds., Textbook 
of Veterinary Internal Medicine, 7th ed. St. 
Louis, MO: Saunders Elsevier, 2010, pp. 79–83.
Consulting Editor  Alexander H. Werner Resnick
available online(continued)  Dermatoses, Erosive or Ulcerative

376  Blackwell’s Five-Minute Veterinary Consult  
DDermatoses, Exfoliative
  BASICS
Excessive or abnormal shedding of epidermal 
cells resulting in the clinical presentation of 
cutaneous scaling.
• An increase in the production, an increase 
in the desquamation, or a decrease in the 
cohesion of keratinocytes results in abnormal 
shedding of epidermal cells individually (fine 
scale) or in sheets (coarse scale).
• Primary exfoliative disorders—keratiniza-
tion defects: genetic control of epidermal cell 
proliferation and maturation is abnormal.
• Secondary exfoliative disorders—disease 
alters the normal maturation and prolifera-
tion of epidermal cells.
• Anomalies in sebaceous or apocrine gland 
function may be present or causative.
• Primary—apparent by 2 years of age; 
characteristic in affected breeds.
• Secondary—any age; any breed of dog or 
cat.
SIGNS
• Dry or greasy collections of fine or coarse 
scale located diffusely throughout the hair 
coat or focally in keratinaceous plaques.
• Oily skin and hair.
• Malodor.
• Comedones.
• Follicular casts.
• Candle wax–like deposits on hair.
• Silver scales, mostly affecting nose, face, 
and ears.
• Alopecia.
• Secondary bacterial folliculitis and/or 
Malassezia  dermatitis.
CAUSES
Primary
• Primary idiopathic seborrhea (primary 
keratinization disorder)—primary cellular 
defect; accelerated epidermopoiesis and 
hyperproliferation of the epidermis, 
follicular infundibulum, and sebaceous 
gland; cocker and springer spaniel, West 
Highland white terrier, basset hound, 
Doberman pinscher, Irish setter, and 
Labrador retriever.
• Vitamin A–responsive dermatosis—young 
cocker spaniels; clinically similar to severe 
idiopathic seborrhea; identified by response 
to oral vitamin A supplementation.
• Zinc-responsive dermatosis—alopecia, dry scaling, crusting, and erythema around the 
eyes, ears, feet, lips, and external orifices; two 
syndromes: young adult dogs (mainly 
Siberian husky and Alaskan Malamute) and 
rapidly growing large-breed puppies; 
nutritionally responsive.
• Ectodermal defects—follicular dysplasias; 
color mutant or dilution alopecia; represent 
anomalies in melanization of the hair shaft 
and structural hair growth; keratinization 
defects theorized as causative for several 
syndromes; Doberman pinscher, Irish setter, 
dachshund, chow chow, Yorkshire terrier, 
poodle, Great Dane, whippet, saluki, and 
Italian greyhound; failure to regrow blue or 
fawn hair with normal “point” hair growth, 
excessive scaliness, comedone formation, 
secondary pyoderma.
• Idiopathic nasodigital hyperkeratosis—
excessive build-up of scale and crusts on the 
nasal planum and footpad margins; possibly a 
senile change; generally asymptomatic; 
spaniels and retrievers; cracking and 
secondary bacterial infection can cause pain.
• Sebaceous adenitis—inflammatory disease 
targeting sebaceous glands and ducts causing 
patchy or diffuse hair loss and excessive scaling; 
tightly adherent follicular casts; standard 
poodle, Akita, Samoyed, German shepherd, 
Havanese, Bernese Mountain dog, and vizsla.
• Ichthyosis—rare and severe congenital 
disorder of keratinization; West Highland 
white terrier, golden retriever, cavalier King 
Charles spaniel, and Norfolk terrier; 
generalized accumulations of scale and crusts 
at an early age; secondary infections (bacterial 
and yeast) common.
• Primary seborrhea in Persian kittens.
Secondary
• Cutaneous hypersensitivity—with pruritus, 
secondary skin trauma, and irritation.
• Ectoparasitism—scabies, demodicosis, and 
cheyletiellosis; with inflammation and 
exfoliation.
• Bacterial folliculitis—bacterial enzymatic 
disadhesion with increased exfoliation of 
keratinocytes.
• Dermatophytosis—increased exfoliation as 
a skin mechanism in resolving infection.
• Cutaneous Leishmaniasis in endemic regions 
of the world; systemic signs might be present.
• Endocrinopathy—hypothyroidism: 
abnormalities in keratinization, failure to 
regrow hair, and excessive sebum production; 
hyperadrenocorticism: abnormal keratiniza-
tion and decreased follicular activity; excessive 
scaling and secondary pyoderma common in 
both syndromes; other hormonal abnormali-
ties may also be associated with excessive 
scaling.
• Age—dull, brittle, and scaly hair coat due 
to alterations caused by natural changes in 
epidermal metabolism associated with age; no 
specific defect identified.• Nutritional disorders—malnutrition and 
generic dog food dermatosis; auto-immune 
dermatoses—pemphigus complex: may 
appear exfoliative; vesicles become scaly and 
crusty; cutaneous and systemic lupus 
erythematosus: cutaneous signs often appear 
as areas of alopecia and scaling.
• Neoplasia—primary epidermal neoplasia 
(epitheliotropic lymphoma): with alopecia 
and scaling as epidermal structures are 
damaged by infiltrating lymphocytes; 
preneoplastic conditions (actinic keratosis): 
initially appear exfoliative.
• Miscellaneous—any disease process may 
result in excessive scale formation due to a 
metabolic disorder or to cutaneous 
• Exfoliative disorders—rare in cats: tail 
gland hyperplasia, feline thymoma-associated 
exfoliative dermatitis.
  DIAGNOSIS
Based on signalment and history (breed-associ -
ated vs. age of onset), presence/absence of 
pruritus (hypersensitivity vs. secondary infection), 
and concurrent signs (endocrinopathy).
• Normal with primary keratinization 
disorders.
• Mild, nonregenerative anemia and 
hypercholesteremia are consistent with 
• Neutrophilia, monocytosis, eosinopenia, 
lymphopenia, elevated serum alkaline 
phosphatase, hypercholesterolemia, and 
hyposthenuria suggest hyperadrenocorticism.
Thyroid hormone levels and adrenal 
function tests if an endocrinopathy is 
suspected; see specific chapters for test 
recommendations. Serology, PCR, cytology, 
and histopathology for Leishmaniasis; see 
specific chapter.
IMAGING
Thoracic radiographs—feline thymoma-
associated exfoliative dermatitis.
• Skin biopsy—rule out particular differential 
diagnoses; strongly recommended for most 
cases.
• Intradermal allergy test.
• Restricted ingredient food trial.
• Cytology of skin surface.
• Microscopic examination of plucked 
hairs—macromelanosomes and structural 
anomalies in follicular dysplasia and color 
dilution alopecia.

Canine and Feline, Seventh Edition  377
D   TREATMENT
• Frequent and adequate topical therapy.
• Diagnose and control treatable primary and 
secondary diseases.
• Recurrence of secondary infections may 
require repeated therapy and further 
• Maintaining control is often lifelong.
• Prioritize restoration of epidermal barrier 
integrity and function.
Shampoos
• Contact time—5–15 minutes required; >15 
minutes discouraged, may result in epidermal 
maceration, loss of barrier function, and 
excessive epidermal drying and irritation.
• Relative keratolytic activity—hypoaller-
genic < sulfur/salicylic acid < benzoyl 
peroxide.
• Ethyl lactate—less keratolytic/less drying; 
useful for moderate bacterial folliculitis and 
dry scale.
• Chlorhexidine—antimicrobial; mildly 
drying; useful for moderate bacterial 
folliculitis and Malassezia  dermatitis.
• Tar—keratolytic, keratoplastic, and 
antipruritic; useful for moderate scale 
associated with pruritus.
Moisturizers/Barrier Restoration
• Restore skin hydration and increases 
effectiveness of subsequent shampoos.
• Humectants—enhance hydration of the 
stratum corneum by attracting water from the 
dermis; at high concentrations may be keratolytic.
• Propylene glycol spray (50–75% dilution 
with water) applied frequently.
• Microencapsulation—may improve residual 
activity of moisturizers by allowing sustained 
release after bathing.
• Emollients—coat the skin; smooth the 
roughened surfaces produced by excessive 
scaling; usually combined with occlusives to 
promote hydration of the epidermis.
• Barrier restoration—phytosphingosines, 
ceramides.
• Specific disease (e.g., thyroxine replacement 
for hypothyroidism).• Systemic antibiotics—secondary pyoderma.
• Retinoids—varied success for idiopathic or 
primary seborrhea; reports of individual 
response in refractory cases; isotretinoin 
(1 mg/kg PO q12–24h); if response is seen, 
taper dosage (1 mg/kg q48h or 0.5 mg/kg 
q24h); difficult to dispense due to strict 
prescription procedures.
• Cyclosporine (modified) 5 mg/kg/day until 
controlled, then decreased to minimal 
effective maintenance dosage for individual 
cases of keratinization disorder associated 
with hypersensitivity, sebaceous adenitis, 
epidermal dysplasia, ichthyosis, and/or 
• Corticosteroids—use judiciously to 
control the inflammation resulting from 
exfoliative disorders; may mask signs of 
pyoderma and prevent accurate diagnosis of 
primary disease.
• Vitamin A and D analogues—side effects 
can be severe; patients should be referred to a 
dermatologist before being treated with these 
drugs; teratogenic.
  FOLLOW-UP
• Antibiotics and topical therapy—monitor 
response every 3 weeks; patients may 
respond differently to the various topical 
therapies.
• Development of additional diseases and 
recurrence of pyoderma—reevaluation critical 
to determine if new factors are involved and if 
changes in therapy are necessary.
• Endocrinopathy—specific laboratory 
testing for disease management.
• Selective autoimmune disorders—clinical 
evaluation and laboratory monitoring 
frequent initially; based on diagnosis and 
treatment protocols.
• Retinoid drugs—serum chemistries, 
including triglycerides, and Schirmer tear 
tests.
Skin aging might be related to increase in 
exfoliative disorders or relapses.ZOONOTIC POTENTIAL
• Dermatophytosis and several ectoparasites 
have zoonotic potential.
• Leishmaniasis is a reportable disease.
Systemic retinoids and vitamin A in 
therapeutic dosages—extreme teratogen; do 
not use in intact females because of severe and 
predictable teratogenicity and extremely long 
withdrawal period; women of childbearing 
age should not handle these medications.
SYNONYMS
• Keratinization disorder, seborrhea, 
idiopathic seborrhea, keratinization defect, 
dyskeratinization.
• Eczema, psoriasis, dandruff—incorrect 
human terms.
• Sebopsoriasis—correct term to describe 
similarities between some human and canine 
keratinization defects.
SEE ALSO
Syndrome)—Cats.
• Leishmaniosis
• Malassezia Dermatitis.
• Sarcoptic Mange.
Gross TL, Ihrke PJ, Walder EJ, Affolter V. 
Skin Diseases of the Dog and Cat: 
Clinical and Histopathologic Diagnosis, 
2nd ed. Oxford: Blackwell Science, 
2005.
and Kirk’s Small Animal Dermatology, 
7th ed. St. Louis, MO: Elsevier, 2013.
Torres SMF , Roudebush P , eds., Advances 
in Veterinary Dermatology, Vol. 8. 
Hoboken, NJ: Wiley, 2017.
Resnick
available online(continued)  Dermatoses, Exfoliative

378  Blackwell’s Five-Minute Veterinary Consult  
D  BASICS
• Neoplastic proliferation of cells derived from 
the skin or migrating to the skin.  • Epidermal 
tumors include those arising from keratinocytes, 
melanocytes, Merkel cells, and Langerhans 
cells, and epitheliotropic lymphoma.  • Adnexal 
tumors include those arising from hair follicles, 
sebaceous glands, and sweat glands.  • Dermal 
and subcutaneous skin tumors include those of 
mesenchymal origin and tumors of round cell 
origin.  • Secondary or metastatic skin tumors 
result from the proliferation of cells from 
primary neoplasms of other organs in the skin.
• Neoplasia develops as a result of changes in 
genes controlling cell proliferation and 
homeostasis.  • More than 100 cancer-related 
genes have been identified.  • Oncogenes 
encode proteins that promote cell growth; 
tumor-suppressor genes encode proteins that 
restrict cell proliferation and differentiation.  
• Mutations in p53, a tumor-suppressor gene, 
are found in approximately 50% of cancers in 
humans and have also been found in many 
tumors affecting dogs and cats.  • Ultraviolet 
light promotes tumor development by 
damaging DNA and suppressing the immune 
system.  • Many viruses promote tumor growth 
through stimulating cell proliferation and/or 
suppressing the immune system.  • Reports of 
specific cutaneous neoplasia associated with 
medications and/or vaccinations.
GENETICS
• Breed predispositions have been reported 
for specific tumors, but the mode of 
inheritance in these breeds has not been 
determined. Mutations in oncogenes and/or 
tumor-suppressor genes (e.g., p53) are present 
in many types of skin tumors.
• The combined incidence rate for skin 
tumors has been reported as 728/100,000 
(0.728%) for dogs and 84/100,000 (0.084%) 
for cats.  •  The skin is the most common site 
of occurrence of neoplasia in the dog (30% of 
total tumors) and the second most common 
site in the cat (20% of total tumors).  
• Canine skin tumors are approximately 55% 
mesenchymal, 40% epithelial, and 5% 
melanocytic.  • The most frequently 
reported cutaneous or subcutaneous tumors 
in descending order for dogs are lipoma, 
sebaceous gland adenoma, mast cell tumor, 
papilloma, and histiocytoma. • Feline skin 
tumors are approximately 50% epithelial, 
48% mesenchymal, and 2% melanocytic.  • The most frequently reported cutaneous or 
subcutaneous tumors in cats are basal cell 
tumor, squamous cell carcinoma, mast cell 
tumor, and fibrosarcoma.  • Skin tumors in 
cats are more frequently malignant; skin 
tumors in dogs are more frequently benign.
Geographic regions near the equator, with 
high altitude, or with sand or other reflective 
surfaces, have a higher incidence of solar-
induced neoplastic dermatoses.
Species
• Canine breeds with the highest overall 
incidence of skin tumors include boxer, 
Scottish terrier, bullmastiff, basset hound, 
Weimaraner, Kerry blue terrier, and 
Norwegian elkhound. • Feline breeds with 
the highest overall incidence of skin tumors 
include Siamese and Persian. • Certain 
breeds are predisposed to specific types of 
tumors (see Suggested Reading). • Dog—
breeds associated with the most common 
cutaneous neoplasms: ◦ Lipoma—cocker 
spaniel, dachshund, Doberman pinscher, 
Labrador retriever, miniature schnauzer, 
Weimaraner. ◦ Sebaceous gland tumor—
beagle, cocker spaniel, dachshund, Irish 
setter, Lhasa apso, Malamute, miniature 
schnauzer, poodle, shih tzu, Siberian husky. 
◦ Mast cell tumor—American Staffordshire 
terrier, beagle, Boston terrier, boxer, bull 
terrier, dachshund, English bulldog, fox 
terrier, golden retriever, Labrador retriever, 
pug, shar-pei, Weimaraner. ◦ Histiocytoma—  
American Staffordshire terrier, Boston terrier, 
boxer, cocker spaniel, dachshund, Doberman 
pinscher, English springer spaniel, Great 
Dane, Labrador retriever, miniature 
schnauzer, Rottweiler, Scottish terrier, 
shar-pei, Shetland sheepdog, West Highland 
white terrier. ◦ Papilloma—cocker spaniel, 
Kerry blue terrier. • Cat—breeds associated 
with the most common cutaneous 
neoplasms: ◦ Basal cell tumor—Persian, 
Himalayan (basal cell carcinoma—Siamese). 
◦ Squamous cell carcinoma—no predisposed 
breed reported. ◦ Mast cell tumor—Siamese. 
◦ Fibrosarcoma—no predisposed breed 
reported.
• The median age for cutaneous neoplasia is 
10.5 years in dogs and 12 years in cats. • The 
peak age period for cutaneous neoplasia in 
dogs and cats is 6–14 years.
• Females have a higher incidence of tumors 
in dogs (56%). • Males have a higher 
incidence of tumors in cats (56%).SIGNS
Most common clinical sign is a cutaneous or 
subcutaneous nodule; some tumors have an 
ulcerated surface; others may result in 
excessive scaling or in the formation of 
cutaneous plaques.
• T umors are most often slow growing; the 
owner may find them during petting, 
bathing, or grooming of the pet. • T umors 
may be rapidly growing and appear (or 
increase in size) quickly (e.g., histiocytoma).
• Nodules—cutaneous or subcutaneous. 
• Cutaneous ulcers. • Excessive scaling. 
• Cutaneous papillomas. • Cutaneous 
plaques.
CAUSES
• Genetic (gene mutations). • Environmental 
(e.g., ultraviolet light, radiation exposure). 
• Viruses (e.g., papillomaviruses, feline 
leukemia virus, feline immunodeficiency virus). 
• Toxins (e.g., tars). • Drugs (e.g., immuno -
suppressive agents, chemotherapeutic agents). 
◦ Epidermal neoplasms: ◦ Keratinocytes—
papillomas, squamous cell carcinoma, basal 
cell carcinoma, basosquamous carcinoma. 
◦ Melanocytes—melanoma. ◦ Merkel 
cells—Merkel cell carcinoma. ◦ Langerhans 
cells—histiocytoma and malignant 
histiocytosis. ◦ Epitheliotropic lymphoma—  
T lymphocytes. • Adnexal neoplasms: ◦ Hair 
follicles—trichofolliculoma, trichoepithelioma, 
infundibular keratinizing acanthoma, 
tricholemmoma, pilomatrixoma, trichoblastoma. 
◦ Sebaceous glands—sebaceous adenoma, 
sebaceous epithelioma, sebaceous 
adenocarcinoma, perianal gland epithelioma, 
perianal gland carcinoma. ◦ Sweat glands—
apocrine cystadenoma, apocrine secretory 
adenoma/adenocarcinoma, apocrine ductal 
adenoma/carcinoma, eccrine carcinoma. 
• Dermal and subcutaneous neoplasms: 
◦ Mesenchymal origin—soft tissue 
sarcoma: fibroma/fibrosarcoma, myxoma/
myxosarcoma, hemangiopericytoma, 
lymphangioma/lymphangiosarcoma, 
hemangioma/hemangiosarcoma, lipoma/
liposarcoma, neurofibrosarcoma, leiomyoma/
leiomyosarcoma, synovioma/synovial 
sarcoma, rhabdomyoma/rhabdomyosarcoma. 
◦ Round cell origin—transmissible venereal 
tumor, mast cell tumor, plasmacytoma, 
lymphoma, histocytoma, and histocytic tumors. 
• Secondary or metastatic skin tumors result 
from the metastasis or primary neoplasms in 
other organs to the skin.
• Hair coat color and length (e.g., hairless 
breeds, white hair coat, lightly pigmented 
skin—increased risk for squamous cell 
carcinoma).  • Age (e.g., young animals Dermatoses, Neoplastic

Canine and Feline, Seventh Edition  379
D
highest risk for viral infections, older 
animals at highest risk for environment-
associated neoplasia).  • Sunlight exposure 
(e.g., dogs and cats that sunbathe or spend 
time outdoors on reflective surfaces have 
higher risk of ultraviolet light–induced 
skin tumors).  • Genetics—certain breeds 
have higher risk of developing specific types 
of tumors (see above and Suggested 
Reading).
  DIAGNOSIS
• Cyst.  • Abscess.  • Inflammatory nodule/
granuloma/plaque—sterile granulomatous and 
pyogranulomatous disease, sterile panniculitis, 
fungal infection, mycobacterial infection, 
foreign body.  • T rauma/self-induced skin 
ulceration.  • Hamartoma/nevus.
N/A
• Cytology (fine-needle aspirate or impression 
smear).  • Regional lymph node aspirate (for 
staging).
IMAGING
Thoracic radiographs and abdominal ultra-  
sonography useful for staging (evaluate for 
metastatic disease or underlying primary 
neoplasia).
• Cytology.  • Biopsy with histopathologic 
examination.  • Immunohistochemistry (useful 
in confirming certain types of tumors).
Varies with tumor type; see specific tumors 
for additional information.
  TREATMENT
• Varies with tumor type. • Observation is 
appropriate for some benign tumors. 
• Surgical excision, cryosurgery, radiation 
therapy, and/or tumor-specific chemotherapy 
or immunotherapy may be curative or 
palliative.
• Varies with tumor type and location.  • T raumatized 
tumors may become secondarily infected.ACTIVITY
Varies with tumor type and location.
DIET
Diets high in omega-3 fatty acids, arginine, 
and protein may be beneficial in boosting the 
immune response and preventing cancer-
associated cachexia.
• Vary with tumor type and location—wide 
margins may be needed to prevent 
reoccurrence of infiltrative tumors. 
• Pretreatment with antihistamines approp -
riate when excising mast cell tumors.
Vary with tumor type—chemotherapy 
protocols are useful in some cases.
Vary with tumor type and presence of 
concurrent disease.
Vary with tumor type and location.
  FOLLOW-UP
• Varies with tumor type and location. 
• Minimize exposure to ultraviolet light to 
help prevent some types of tumors.
Vary with tumor type and location.AGE-RELATED FACTORS
None
Varies with tumor type; some may have a 
genetic predisposition.
SYNONYMS
N/A
SEE ALSO
• Adenocarcinoma, Skin (Sweat Gland, 
Sebaceous).
• Basal Cell T umor.
• Lipoma, Infiltrative.
• Malignant Fibrous Histiocytoma.
• Mast Cell T umors.
• Papillomatosis.
• http://www.oncolink.org/types/section.
cfm?c=22&s=69
• http://www.vetcancersociety.org
Campbell KL, ed. Small Animal Dermatology 
Secrets. Philadelphia, PA: Hanley & Belfus, 
2004, pp. 385–458.
Goldschmidt MH, Shofer FS. Skin T umors of 
the Dog and Cat. Oxford: Butterworth 
Heinemann, 1992.
Gross TL, Ihrke PJ, Walder EJ, et al. Skin 
Diseases of the Dog and Cat: Clinical and 
Histopathologic Diagnosis, 2nd ed. Oxford: 
Blackwell, 2005, pp. 561–893.
Martin PD, Argyle DJ. Advances in the 
management of skin cancer. Vet Dermatol 
2013, 24:173–180.
Miller WH, Griffin CE, Campbell KL, eds. 
7th ed. Philadelphia, PA: Elsevier, 2013, pp. 
774–843.
Shearer D, Dobson J. An approach to nodules 
and draining sinuses. In: Foster A, Foil C, 
BSAVA Manual of Small Animal 
Dermatology, 2nd ed. Gloucester: BSAVA, 
pp. 55–65.
Author  Karen L. Campbell
Resnick(continued)  Dermatoses, Neoplastic

380  Blackwell’s Five-Minute Veterinary Consult  
DDermatoses, Papulonodular
  BASICS
• Diseases whose primary lesions manifest as 
papules and nodules.
• Papule—solid, elevated lesion of the skin 
less than 1 cm in diameter.
• Nodule—solid, elevated lesion of the skin 
more than 1 cm in diameter that extends into 
deeper layers of the skin.
• Papules—usually the result of tissue 
infiltration by inflammatory cells; accompanying 
intraepidermal edema or epidermal hyperplasia 
and dermal edema.
• Nodules—usually the result of a massive 
infiltration of inflammatory or neoplastic cells 
into the dermis or subcutis.
GENETICS
Determined by cause; specific diseases may be 
more commonly seen in certain breeds.
Species
SIGNS
• Papules and/or nodules with distribution 
characteristic of the cause.
• Accompanying crusting, inflammation, 
pigmentation changes, and hair coat changes 
often noted; also characteristic of the cause.
CAUSES
• Superficial and deep bacterial folliculitis 
(e.g., Staphylococcus ).
• Other bacterial—mycobacterial, actinomy­
cosis, nocardiosis, abscess.
• Fungal—dermatophytosis (including 
pseudomycetoma/kerion), histoplasmosis, 
cryptococcosis, coccidiomycosis, sporo­
trichosis, blastomycosis, phaeohyphomycosis.
• Sebaceous adenitis, granulomatous.
• Canine and feline acne.
• Parasitic—demodicosis, Leishmaniasis, flea 
bite hypersensitivity, sarcoptic mange, pelodera 
• Sterile nodular—sterile pyogranulomatous 
dermatitis and panniculitis, reactive histiocytosis.• Metabolic—cutaneous xanthomatosis, 
calcinosis circumscripta.
• Hypersensitivity—feline eosinophilic 
• Bacterial folliculitis, dermatophytosis, and 
demodicosis—any disease or medication that 
causes immune compromise or interferes with 
the barrier function of the skin.
• Pelodera dermatitis—may be associated with 
contact with decaying organic debris (straw or 
hay) containing Pelodera strongyloides .
  DIAGNOSIS
Usually normal—determined by cause.
IMAGING
N/A
• Skin scraping—parasites.
• Dermatophyte cultures—dermatophytes.
• Pustule (if present) impression smear 
cytology—bacteria and degenerative 
neutrophils compatible with bacterial 
folliculitis; eosinophils can be compatible 
with hypersensitivity and/or with rupturing 
folliculitis or furunculosis; acantholytic 
keratinocytes consistent with an inflamma­
tory folliculitis or pemphigus disease.
• Culture from tissue (fungal, bacterial, myco  ­ 
bacterial)—identify deep/systemic infection; 
possible susceptibility report for treatment.
• Aspirate and cytology from nodule—identify 
cellular infiltrate; presence of organisms.
• Skin biopsy— determine definitive 
diagnosis; especially if baseline diagnostic 
procedures are normal and/or initial empiric 
treatment is ineffective.
Depends upon underlying disease process.
  TREATMENT
• Outpatient for nearly all causes (except 
some cases of neoplasia).
• Generalized demodicosis with secondary 
sepsis requires hospitalization.
Depends upon underlying issue.ACTIVITY
No specific alteration of activity 
DIET
No specific alteration of diet recommended.
• For fungal infections, treatment may be 
expensive and prognosis can be guarded for 
deep/systemic fungal infections.
• For immune ­mediated processes, treatment 
may be for the duration of the patient’s life.
Rarely necessary unless neoplasia is diagnosed.
Bacterial Folliculitis
• Superficial pyoderma—appropriate 
antibiotics based on bacterial culture and 
susceptibility testing for at least 3–4 weeks, or 
1 week beyond resolution of clinical signs.
• Deep pyoderma—appropriate antibiotics 
based on bacterial culture and susceptibility 
testing for at least 6–8 weeks, or 2 weeks 
beyond resolution of clinical signs.
• Identify and control underlying cause to 
prevent recurrence.
• See Pyoderma for additional recomm  ­ 
endations.
Sebaceous Adenitis
• Appropriate antibiotics if secondary 
bacterial infection present.
• Propylene glycol and water (50–75% 
dilution) once daily as a spray to affected 
areas helpful in mild cases.
• Essential fatty acid dietary supplements 
(omega ­3 and omega ­6 PO).
• Topical therapy—antiseborrheic shampoos, 
emollient rinses (baby oil), and humectants.
• Cyclosporine, modified (5 mg/kg PO q24h).
• Vitamin A (10,000–30,000 IU PO daily or 
1000 IU/kg PO daily).
• Refractory cases—isotretinoin (1 mg/kg 
PO q12–24h); if response is seen, taper 
dosage (1 mg/kg q48h or 0.5 mg/kg q24h); 
the synthetic retinoids have become 
difficult to dispense due to strict prescrip ­
tion procedures.
• Most cases are refractory to corticosteroids.
• See Sebaceous Adenitis, Granulomatous for 
additional recommendations.
Canine and Feline Acne
• May resolve without therapy in mild cases.
• Warm water soaks or Epsom salt solution 
(2 T/quart or 30 m/L of water) for 5–10 min.
• Chlorhexidine ­based pads, or acetic acid/
boric acid pads/wipes, or benzoyl peroxide 
gels used daily or alternated daily; topical 
ceramide/EFA preparations may be helpful.

Canine and Feline, Seventh Edition  381
D
• Topical creams/ointments—mupirocin 2% 
ointment: topical antibiotic; apply q24h; 
should not be used in cats with deep lesions; 
metronidazole, 0.05% Vitamin A acid cream, 
clindamycin are alternative options.
• Secondary bacterial infection—systemic 
• Underlying cause(s) should be determined 
and treated accordingly.
• Refractory cases—isotretinoin (1–2 mg/kg 
PO q24h); oral synthetic retinoids have 
become difficult to dispense due to strict 
prescription procedures; prednisolone PO 
(1–2 mg/kg/day for 10–14 days and taper) 
may reduce scar tissue formation.
• See Acne—Cats and Acne—Dogs for 
Pelodera Dermatitis
• Remove and destroy bedding.
• Wash kennels, beds, and cages and treat 
with a premise insecticide or flea spray.
• Bathe affected animal and remove crusts.
• Parasiticidal dip or ivermectin as recom­
mended for sarcoptic mange.
• Corticosteroids as needed for inflammation.
• Severe infection—may require use of 
Sterile Nodular Dermatoses
• Attempt to identify underlying cause.
• Cyclosporine, modified 5 mg/kg PO q24h.
• Tetracycline (250 mg <10 kg, 500 mg 
>10 kg q8–12h), doxycycline (10 mg/kg 
q24h), or minocycline (5 mg/kg q12h) with 
niacinamide (250 mg <10 kg, 500 mg >10 kg 
q8–12h).
• Corticosteroids at immunosuppressive 
doses and taper according to response.
• Chemotherapeutic drugs (chlorambucil or 
azathioprine or mycophenolate mofetil).
Other
• Dermatophytosis—itraconazole, 
ketoconazole, or terbinafine; see 
• Kerion—see Dermatophytosis.
• Demodicosis/sarcoptic mange—see 
Demodicosis, Sarcoptic Mange.
• Other bacterial infection—antibiotics 
dependent upon culture and sensitivity 
results.
• Deep/systemic fungal infection.
• Feline eosinophilic dermatitis—look for 
• Neoplasia—see Dermatoses, Neoplastic.
medications should be avoided with 
folliculitis, dermatophytosis, kerion, and 
demodicosis.PRECAUTIONS
with ketoconazole than with other azoles in cats.
• Cats can be sensitive to the irritant effects 
of benzoyl peroxide.
• Fatty acids—use with caution in dogs with 
inflammatory bowel disease or recurrent 
• Isotretinoin—may cause keratoconjunctivi­
tis sicca, hyperactivity, pinnal pruritus, 
erythematous mucocutaneous junctions, 
swollen tongue, lethargy with anorexia or 
vomiting, abdominal distension, or collapse; 
CBC and chemistry screen abnormalities 
include high platelet count, hypertriglyceri­
demia, hypercholesterolemia, and high 
alanine transaminase; teratogen.
• Cyclosporine—may cause vomiting and 
diarrhea, gingival hyperplasia, B lymphocyte 
hyperplasia, hirsutism, papillomatous skin 
eruptions, and increased incidence of 
infection; decreased glucose homeostasis; 
potential toxic reactions rare and include 
nephrotoxicity and hepatotoxicity.
• Azathioprine, mycophenolate mofetil, and 
chlorambucil—potential for bone marrow 
suppression, gastrointestinal upset; 
azathioprine can cause hepatotoxicity and 
possibly pancreatitis.
• Cyclosporine and corticosteroids interact 
with several medications; an appropriate 
drug formulary should be consulted prior 
to usage.
• Referral to a veterinary dermatologist 
should be considered if the etiology remains 
undetermined and/or prior to prescribing 
unfamiliar medications.
N/A
  FOLLOW-UP
• CBC, chemistry screen, urinalysis, and 
urine cultures—monitor periodically in 
patients receiving immunosuppressive 
medications; monitoring will depend upon 
medication and dosage.
• CBC, chemistry screen, and urinalysis—
monitor monthly for 4–6 months in patients 
receiving synthetic retinoid therapy.
• Tear production—monitor monthly for 
4–6 months, then every 6 months in patients 
receiving synthetic retinoid therapy or 
sulfonamide ­containing antibiotics.
• Skin scraping—monitor therapy in patients 
with Demodicosis (see Demodicosis).• Repeat fungal culture—monitor therapy in 
patients with dermatophytosis (see 
Dermatophytosis).
• Resolution of lesions—monitor progress of 
sebaceous adenitis, actinic conditions, and all 
other diseases.
Dependent upon specific disease.
N/A
N/A
• Dermatophytosis—incidence in humans 
reported in 30–50% of cases of Microsporum 
canis, but possible with all dermatophytosis cases.
• Fungal infections—potential depends upon 
organism.
• Synthetic retinoids—teratogens; do not use in 
pregnant animals, animals intended for 
reproduction, or intact female animals; should 
not be handled by women of childbearing age.
• Corticosteroids—avoid use in pregnant animals.
• Cyclosporine—avoid during pregnancy 
unless necessary; dosages two to five times 
normal have been fetotoxic and embryotoxic 
in rats and rabbits.
• Antifungal agents should be avoided in 
pregnant animals.
• All drugs should be used with caution in 
pregnant and breeding animals.
SEE ALSO
Five­Minute Veterinary Consult Clinical 
ed. Hoboken, NJ: Wiley ­Blackwell, 2018.
Author  Karen A. Kuhl
Resnick
available online(continued)  Dermatoses, Papulonodular

382  Blackwell’s Five-Minute Veterinary Consult  
D  BASICS
Sterile diseases with primary lesions of 
nodules and/or plaques.
• Nodules/plaques—usually result from an 
infiltration of inflammatory cells into the 
dermis and subcutis; may be secondary to 
endogenous or exogenous stimuli.
• Inflammation is typically, but not always, 
granulomatous to pyogranulomatous.
GENETICS
Oligogenic transmission is proposed for 
histiocytic sarcoma for Bernese mountain 
dogs.
• Collagenous nevi—German shepherd dogs 
3–5 years old.
• Calcinosis circumscripta—German 
shepherd dogs <2 years old.
• Systemic histiocytosis and malignant histiocyto -
sis—Bernese mountain dogs (primarily), 
Rottweilers, and retrievers (golden and Labrador).
• Eosinophilic granuloma—Siberian huskies 
<3 years, males.
SIGNS
• Characterized by single to multiple dermal 
to subcutaneous nodules and/or plaques.
• Firm to fluctuant.
• Occasionally painful.
• Overlying epidermis may be normal to 
CAUSES
• Foreign body reaction.
• Spherulocytosis.
• Idiopathic sterile granuloma and 
pyogranuloma.
• Canine eosinophilic granuloma.
• Calcinosis cutis.
• Calcinosis circumscripta.
• Reactive (cutaneous, systemic) or malignant 
histiocytosis (disseminated histiocytic sarcoma).
• Collagenous nevi (nodular dermatofibrosis).
• Cutaneous xanthoma.
• Foreign body reaction—induced by 
exposure to any irritating material.
• Calcinosis cutis—increased risk with 
exposure to high doses of exogenous or 
endogenous glucocorticosteroids.
• Panniculitis—increased risk with vitamin 
E–deficient diet.• Cutaneous xanthoma—high-fat treats or 
diet, diabetes mellitus, hyperlipidemia.
  DIAGNOSIS
• Sterile nodular dermatoses must be 
differentiated from deep bacterial and fungal 
infections and dermal neoplasia.
• Diagnosis by histopathology and deep 
tissue cultures.
• Immunohistochemistry—differentiating 
histiocytic conditions.
• Immunohistochemical staining and PCR 
testing—diagnose Leishmaniasis and myco  - 
• Amyloidosis—possible changes in 
biochemistry and/or urinalysis if internal 
organs are affected.
• Malignant histiocytosis—pancytopenia.
• Calcinosis cutis—changes characteristic of 
hyperglucocorticoidism.
• Cutaneous xanthomas—may have 
glucosuria, hyperglycemia, and/or lipid 
profile abnormalities.
• Sterile panniculitis—possible biochemistry 
changes associated with pancreatitis, hepatic 
disease, or systemic lupus erythematosus.
IMAGING
Radiology and ultrasonography—involvement 
of internal organs in amyloidosis and histiocy -
tosis; areas of dystrophic calcification and/or 
adrenal enlargement or tumor in dogs with 
calcinosis cutis; renal or uterine tumors in 
German shepherd dogs with collagenous nevi.
• Skin biopsy for histopathology and cultures 
(fungal, aerobic, anaerobic, and mycobacterial).
• Biopsies should be excisional and taken 
from an intact or early (nondraining) nodule 
if possible.
• Culture samples should be taken from 
nodular tissue, not exudates.
• Special histopathologic stains for bacteria, 
mycobacteria, and fungi.
• Amyloidosis—accumulation of amorphous 
eosinophilic deposits that may extend into the 
subcutis; deposits stain apple green with 
Congo red in polarized light.
• Foreign body reaction—suppurative to 
pyogranulomatous inflammation that affects 
the dermis, subcutis, and occasionally the 
underlying muscle.
• Spherulocytosis—histiocytes surrounding 
thin-walled parent bodies filled with homo -
geneous eosinophilic spherules.
• Idiopathic sterile granuloma and pyogranu -
loma—granulomatous to pyogranulomatous inflammation that can extend from the dermis 
to the panniculus; differentiated from infectious 
diseases by obtaining negative cultures.
• Canine eosinophilic granuloma—accumu-
lation of eosinophils with edema, possible 
mucin, and collagen degeneration.
• Calcinosis cutis—diffuse calcium deposi-
tion of the dermal collagen and adnexa that 
may extend into the deeper tissue.
• Calcinosis circumscripta—focal to multi  - 
focal deposits of mineral that efface the soft 
tissue.
• Reactive histiocytosis (cutaneous and 
systemic)—markedly angiocentric infiltrate of 
histiocytes that do not form granulomas or 
pyogranulomas.
• Malignant histiocytosis (disseminated histio-  
cytic sarcoma)—dense pleomorphic cell 
proliferation of spindle or round cells that 
efface normal tissue architecture; tumors from 
other spindle and round cell tumors differenti -
ated by immunohistochemistry; see specific 
chapters.
• Sterile nodular panniculitis—neutrophilic 
to pyogranulomatous inflammation that 
affects the deep dermis and panniculus 
predominantly; adipocytes may be necrotic or 
may be infiltrated by foamy macrophages; 
differentiated from infectious diseases by 
obtaining negative cultures.
• Collagenous nevi—focal but often subtle 
dermal thickening of normal collagen 
bundles.
• Cutaneous xanthoma—diffuse granu -
lomatous inflammation composed of large 
foamy macrophages; lakes of extracellular 
amorphous lipid deposits and cholesterol 
clefts.
  TREATMENT
• Most of these disorders can be treated on an 
• Neoplastic or metabolic disorders may 
require hospitalization and supportive care.
Gentle bathing and soaking to clean the skin 
and remove debris.
DIET
Animals with xanthoma should be on a 
low-fat diet.
• Malignant histiocytosis, amyloidosis, 
collagenous nevi of German shepherd dogs, 
and systemic reactive histiocytosis are almost 
always fatal.
• Prognoses for cutaneous reactive histiocytic 
disease, sterile panniculitis, and sterile 
pyogranuloma are guarded since they may Dermatoses, Sterile Nodular/Granulomatous

Canine and Feline, Seventh Edition  383
Drequire long-term immunosuppressive 
therapy; a few of these cases will not respond 
to therapy at all.
• Amyloidosis—no known therapy, unless 
the lesion is solitary and can be surgically 
removed.
• Spherulocytosis—only effective treatment is 
surgical removal.
pyogranuloma:
◦ Prednisolone (2.2–4.4 mg/kg divided 
PO q12h) is the first line of therapy; 
continue steroids for 7–14 days after 
complete remission, then taper dose.
◦ Azathioprine (2.2 mg/kg q48h) or 
cyclosporine (modified, 5–10 mg/kg q24h) 
added as a steroid-sparing drug.
• Foreign body reactions—removal of the 
offending substance; secondary deep bacterial 
infections require treatment with both topical 
and systemic antibiotics.
• Canine eosinophilic granuloma—predniso-
lone (1.1–2.2 mg/kg PO q24h) usually 
effective.
• Cutaneous/systemic or malignant histiocy-
tosis—no effective long-term therapy; see 
Histiocytosis, Cutaneous.
• Calcinosis cutis—underlying disease must 
be controlled if possible; most cases require 
antibiotics to control secondary bacterial 
infections; hydrotherapy and frequent 
bathing in antibacterial shampoos minimize 
secondary infection; topical dimethyl 
sulfoxide (DMSO) is useful (applied to no 
more than one-third of the body once daily 
until lesions resolve); if lesions are extensive, 
serum calcium levels should be monitored 
closely while using DMSO.
• Calcinosis circumscripta—surgical 
excision.
• Sterile nodular panniculitis:
◦ Single lesions can be removed surgically.
◦ Prednisolone (2.2–4.4 mg/kg PO q24h or 
divided PO q12h) treatment of choice; 
administer until lesions regress, then taper; 
some dogs remain in long-term remission, 
others require prolonged alternate-day therapy.
◦ Azathioprine (2.2 mg/kg q48h) can be 
used together with prednisolone as a 
corticosteroid-sparing agent.◦ Cyclosporine, modified (5–10 mg/kg 
24h) can be used together with predniso-
lone or as an alternative to glucocorticos-
teroid therapy if the patient is steroid 
intolerant or steroids are not sufficiently 
◦ Tetracycline (250 mg <10 kg, 500 mg 
q24h), or minocycline (5 mg/kg q12h) 
with niacinamide (250 mg <10 kg, 500 mg 
>10 kg q8–12h) can also be used as an 
alternative to glucocorticoid therapy; this is 
effective only in mild cases.
• Collagenous nevi—no therapy for most 
cases since cystadenocarcinomas are usually 
bilateral; for rare unilateral case of cystadeno-
carcinoma or cystadenoma, removal of single 
affected kidney may be helpful; ovariohyster-
ectomy should be performed in intact females 
to remove leiomyomas.
• Cutaneous xanthoma—correction of 
underlying diabetes mellitus or hyperlipopro-
teinemia usually curative.
Corticosteroids and other immunosuppressive 
drugs should be avoided, if possible, in any 
animal with secondary bacterial folliculitis.
DMSO—handle with care; monitor serum 
calcium levels if used to treat calcinosis cutis.
  FOLLOW-UP
• Patients on long-term immunosuppressive 
therapy should have CBC, chemistry screen, 
urinalysis, and urine culture performed at 
least every 6 months.
• Dogs treated with DMSO for calcinosis 
cutis should have calcium levels checked every 
7–14 days for first month of therapy if large 
areas are affected.
Long-term use of immunosuppressive therapy 
(especially glucocorticosteroids) may make 
patients more susceptible to other dermatoses 
such as bacterial folliculitis, demodicosis, and 
dermatophytosis, as well as systemic side effects.
• Systemic amyloidosis, malignant histiocyto-
sis, systemic reactive histiocytosis, and 
nodular dermatofibrosis—invariably fatal.• Many of the other conditions have a 
guarded prognosis; many require lifelong 
immunosuppressive therapy to remain in 
remission.
• Calcinosis cutis—hyperglucocorticoidism, 
chronic renal failure, and diabetes mellitus.
• Calcinosis circumscripta—(occasionally) 
hypertrophic osteodystrophy and idiopathic 
polyarthritis.
• Collagenous nevi—renal cystadenoma/
cystadenocarcinoma and uterine, leiomyoma/
leiomyosarcoma.
• Cutaneous xanthoma—diabetes mellitus 
and hyperlipoproteinemia.
SEE ALSO
• Adenocarcinoma, Renal.
• DMSO = dimethyl sulfoxide
http://www.histiocytosis.ucdavis.edu
2018.
O’Kell AL, Inteeworn N, Diaz SF , et al. 
Canine sterile nodular panniculitis: 
retrospective study of 14 cases. J Vet Intern 
Med 2010, 24:278–284.
Santoro D, Prisco M, Ciaramella P . 
Cutaneous sterile granulomas/pyogranulo-
mas, leishmaniasis and mycobacterial 
infections. J Small Anim Pract 2008, 
49:552–561.
Schissler J. Sterile pyogranulomatous 
dermatitis and panniculitis. Vet Clin Small 
Anim 2019, 49:27–36.
Author  Dawn E. Logas
Resnick
available online(continued)  Dermatoses, Sterile Nodular/Granulomatous

384  Blackwell’s Five-Minute Veterinary Consult  
DDermatoses, Sun-Induced
  BASICS
OVERVIEW
The hair coat and epidermal pigmentation 
protect the skin from damage caused by UV 
light radiation. Excessive UV exposure 
damages keratinocytes (producing mutation), 
causes inflammation, and decreases cutaneous 
immune system surveillance. UVA (320–400 nm) 
penetrates more deeply than UVB (290–
320 nm). Prolonged and repeated damage 
leads to preneoplastic changes and eventual 
neoplasia. Prolonged sun exposure in darkly 
pigmented individuals may cause thermal 
burn. UV exposure may exacerbate 
symptoms of pemphigus erythematosus (PE), 
discoid lupus erythematosus (DLE), systemic 
lupus erythematosus (SLE), and dermato  - 
myositis.
• Dogs—Dalmatian, bull terrier, boxer, 
bulldog, basset hound, beagle, whippet, 
American Staffordshire terrier, Australian 
shepherd (nasal solar dermatitis).
• Cats—white cats.
SIGNS
• Dogs—glabrous areas especially axillae, 
flanks, ventral abdomen, lateral extremities.
• Cats—pinnae, nasal planum, dorsal muzzle, 
eyelids.
• Solar dermatitis—photodermatitis.
◦ Nasal—erythema and scaling at junction 
of haired and hairless skin of nose; expands 
caudally followed by scarring.
◦ T runcal—erythema, scaling, and lichenifi -
cation; gradual palpable thickening of white 
areas (adjacent dark areas are normal), 
comedones; secondary deep pyoderma.
• Actinic keratosis— premalignant epithelial 
dysplasia capable of becoming invasive 
squamous cell carcinomas (SCC); indurated, 
crusted, hyperkeratotic plaques.
• Hemangioma—well-circumscribed plaques 
or nodules, firm to fluctuant, bluish to 
purplish.
• Hemangiosarcoma—poorly circumscribed 
dermal dark red to purple, fluctuant nodules; 
may become large; commonly ulcerate and 
bleed; subcutaneous hemangiosarcomas 
usually not solar induced.
• SCC—proliferative and ulcerated plaques; 
easily traumatized; secondary pyoderma 
common; locally invasive and slow to metastasize.
• Solar-induced thermal burn (dorsal thermal 
necrosis)—alopecia, erythema, ulceration, 
eschars/necrosis, and crusts on the dorsal 
parts of the body; dogs with dark shorthair 
coats at increased risk.
• Cutaneous horns—firm hornlike projec-
tions, may originate from actinic keratoses, 
SCC, or other neoplasia; the base of a horn 
must be inspected for underlying cause.CAUSES & RISK FACTORS
• White-haired and lightly haired individuals 
with poorly pigmented skin.
• History of sunbathing.
• Outdoor housing.
• Regions with greater sun exposure, high 
altitudes; usually occurs in summer, but also 
in winter as result of reflection from snow.
  DIAGNOSIS
• DLE.
• PE.
• Drug eruption.
• Chemical burn.
• Biopsy/histopathology—definitive 
• Solar dermatitis—epidermal hyperplasia, 
apoptotic keratinocytes, perivascular 
inflammation, vascular dilatation, dermal 
fibrosis and elastosis.
• Actinic keratosis—parakeratotic hyper -
keratosis with epidermal atypia and solar 
elastosis.
• Hemangioma—proliferative blood-filled 
vascular channels with minimal atypia or 
mitosis.
• Hemangiosarcoma—invasive proliferation 
of atypical endothelial cells with areas of 
vascular space formation.
• SCC—invasion of dermis by keratinocytes; 
keratin “pearls,” mitoses, atypia.
• Solar-induced thermal burn—partial/full 
thickness necrosis of the epidermis, adnexa, 
dermis; coagulation necrosis.
  TREATMENT
• Sun avoidance—keep indoors during day; 
avoid reflected sunlight; apply waterproof 
(>30 SPF) sunscreen (without zinc oxide 
and PABA); sun-protective clothing.
• Surgical excision of neoplastic lesions.
• Cyclooxygenase-2 (COX2) inhibitors—
overexpression by sun-damaged cells; 
inhibition of COX2 demonstrated improve-
ment: firocoxib 5 mg/kg/day PO.
• Glucocorticoids—reduced inflammation 
noted in acute cases; prednisolone 0.5–1 mg/kg PO tapering dosage; discontinue when 
possible.
• Imiquimod 5% cream—induces local 
immune response; for individual lesions, esp. 
actinic keratosis; apply q48h until resolution.
• Cryosurgery—actinic keratosis, SCC.
• Antibiotics—control secondary pyoderma 
(see Pyoderma).
Firocoxib—gastrointestinal upset; elevated 
liver enzymes.
  FOLLOW-UP
• Patients should be regularly screened for 
development and removal of new lesions.
• Sun-induced dermatoses rarely metastasize.
• Long-term therapy necessary following 
extended periods of sun damage.
• COX2 = cyclooxygenase-2.
• DLE = discoid lupus erythematosus.
• SCC = squamous cell carcinoma.
Albanese F , Abramo F , Caporali C, et al. 
Clinical outcome and cyclo-oxygenase-2 
expression in 5 dogs with solar dermatitis/
actinic keratosis treated with firocoxib. Vet 
Dermatol 2013, 24(6):606–e147.
Burrows AK. Actinic dermatoses and sun 
protection. In: Kirk’s Current Veterinary 
Therapy XV. St. Louis, MO: Elsevier, 2014, 
pp. 480–482.
Author  Clarissa P . Souza
Resnick

Canine and Feline, Seventh Edition  385
DDermatoses, Vesiculopustular
  BASICS
• Pustule—small ( <1 cm), circumscribed 
elevation of the epidermis filled with pus.
• Vesicle—small ( <1 cm), circumscribed 
elevation of the epidermis filled with clear 
fluid.
Pustules and vesicles—produced by edema, 
acantholysis (pemphigus), ballooning degenera -
tion (viral infections), proteolytic enzymes from 
neutrophils (pyoderma), degeneration of basal 
cells (lupus), or dermoepidermal separation 
(bullous pemphigoid).
• Lupus—collies, Shetland sheepdogs, and 
German shepherd dogs may be predisposed.
• Pemphigus erythematosus—collies and 
• Pemphigus foliaceus—Akitas, chow chows, 
dachshunds, bearded collies, Labrador 
retrievers, Newfoundlands, Doberman 
pinschers, and schipperkes may be predisposed.
• Bullous pemphigoid—collies and 
Doberman pinschers may be predisposed.
• Dermatomyositis—young collies and 
• Subcorneal pustular dermatosis—schnau-
zers affected most frequently.
• Linear immunoglobulin (Ig) A dermato-
sis—dachshunds exclusively; very rare.
• Dermatophytosis—young animals.
SIGNS
N/A
CAUSES
Pustules/Vesicles
• Superficial pyoderma—impetigo, superfi-
cial spreading pyoderma, superficial bacterial 
folliculitis, canine or feline acne.
• Pemphigus complex—pemphigus foliaceus, 
pemphigus erythematosus, panepidermal 
pemphigus; pemphigus vulgaris produces 
deep clefts that rapidly erode into ulcers.
• Subcorneal pustular dermatosis.
• Sterile eosinophilic pustulosis.
• Linear IgA dermatosis.
• Systemic lupus erythematosus (SLE).
• Discoid lupus erythematosus (DLE).
• Bullous pemphigoid
• Dermatomyositis.
• Cutaneous drug eruption.
• Epidermolysis bullosa.
• Drug exposure—SLE and bullous 
pemphigoid.• Bacterial folliculitis usually secondary to a 
predisposing factor (e.g., demodicosis, 
hypothyroidism, allergy, or corticosteroid 
administration).
• UV light—pemphigus erythematosus, 
bullous pemphigoid, SLE, DLE, and 
dermatomyositis.
  DIAGNOSIS
Superficial Pyoderma
• Most common cause.
• Readily responds to appropriate antibiotic 
therapy if underlying cause is effectively managed.
• Intact pustule—direct smear reveals 
neutrophils engulfing bacteria; most often 
Staphylococcus pseudintermedius ; biopsy 
demonstrates intraepidermal neutrophilic 
pustules or folliculitis with bacteria.
Pemphigus Complex
• Group of immune-mediated diseases 
characterized histologically by disadhesion of 
keratinocytes within the epidermis (acantho-
lytic keratinocytes).
• Direct smears—many acantholytic 
keratinocytes, nondegenerate neutrophils, 
eosinophils, and few to no bacteria.
• Culture of an intact pustule negative.
• Direct immunofluorescence—deposits in 
the intercellular spaces of the epidermis in 
approximately 50% of cases.
• Tends to wax and wane irrespective of 
antibiotic therapy; responds to immunosup-
pressive therapy.
• Pemphigus foliaceus and erythematosus—
superficial acantholysis leading to erosions; 
face, pinnae, and footpads (foliaceus) 
commonly affected; mucous membranes not 
affected; biopsy: subcorneal acantholysis; 
interface and lichenoid inflammation with 
pemphigus erythematosus.
• Pemphigus vulgaris—severe and deep form 
of pemphigus; characterized by erosions 
rapidly leading to ulcerations of oral cavity, 
mucocutaneous junctions, and skin; biopsy: 
suprabasal acantholysis and cleft formation.
• Direct immunofluorescence positive at the 
intercellular spaces of the deeper epidermis.
Subcorneal Pustular Dermatosis
• Rare idiopathic pustular dermatosis of dogs.
• Tends to wax and wane.
• Intact pustules—direct smears reveal 
numerous neutrophils, no bacteria, and 
occasional acantholytic keratinocytes; cultures 
negative.
• Direct immunofluorescence negative.
• Poor response to glucocorticosteroids and 
Dermatophytosis
• Common disease of both dogs and cats.• Dermatophyte culture positive.
• Secondary bacterial folliculitis common.
• Skin biopsy—folliculitis with fungal 
elements.
Sterile Eosinophilic Pustulosis
• Rare idiopathic dermatosis of dogs.
• Direct smears—numerous eosinophils, 
nondegenerate neutrophils, occasional 
acantholytic keratinocytes, and no bacteria.
• Biopsy—eosinophilic intraepidermal 
pustules, folliculitis, and furunculosis.
• Rapid response to glucocorticosteroids.
Linear IgA Dermatosis
• Rare idiopathic dermatosis of dachshunds.
• Pustules—sterile and subcorneal.
• Direct immunofluorescence positive for IgA 
at basement membrane zone.
SLE
• Multisystemic disease with variable clinical 
signs and cutaneous manifestations, including 
mucocutaneous ulceration.
basement membrane zone.
• Antinuclear antibody (ANA) positive.
DLE
• Affects only the skin; lesions usually 
confined to the head.
• Depigmentation, erythema, and ulceration 
of the nasal planum common.
• Skin biopsy—interface and lichenoid 
• ANA negative.
Bullous Pemphigoid
• Ulcerative disorder of the skin and/or 
mucous membranes.
• Skin biopsy—subepidermal cleft formation.
• No acantholysis.
• Idiopathic inflammatory disease of the skin 
and muscle of young collies and Shetland 
sheepdogs; seen rarely in adult animals.
• Lesions affect the face, ear tips, tail tip, and 
pressure points of the extremities.
• Characterized by alopecia, crusting, 
pigmentation disturbances, erosions/
ulceration, and scarring.
• Skin biopsy—follicular atrophy, perifolliculitis, 
and hydropic degeneration of the basal cells.
• Muscle biopsy and electromyography 
(EMG)—evidence of inflammation.
• SLE—possible anemia, thrombocytopenia, 
or glomerulonephritis.

386  Blackwell’s Five-Minute Veterinary Consult  
D• Eosinophilic pustular dermatosis—most 
affected dogs have peripheral eosinophilia.
ANA titer—may be positive with SLE.
• Direct smear from intact pustule/vesicle.
• Culture of intact pustule/vesicle.
• Skin biopsy for histopathology.
• Direct immunofluorescence, including IgA.
• EMG—fibrillation potentials (rapid, irregular, 
and unsynchronized contraction of muscle fibers) 
and positive sharp waves in dermatomyositis.
• Muscle biopsy—myofibril degeneration, 
characterized by fragmentation, vacuolation, 
atrophy, fibrosis, and regeneration in dermato  - 
myositis.
  TREATMENT
• Periodic bathing with an antimicrobial 
shampoo—helps remove surface debris and 
control secondary bacterial folliculitis.
• Usually treated as outpatient.
• SLE, pemphigus vulgaris, and bullous 
pemphigoid may be life-threatening and 
require inpatient intensive care.
See specific disease chapters for more 
information.
• Empiric choices—cephalexin (22 mg/kg 
PO q12h); clindamycin (11 mg/kg PO 
q24h); amoxicillin–clavulanic acid (12.5–
15 mg/kg PO q12h).
• Appropriate antibiotic choice based on 
cultures from intact pustules.
Pemphigus Complex/Bullous Pemphigoid
Immunosuppressive/combination therapy:
• Corticosteroids—prednisolone 2.2–4.4 mg/
kg PO tapering dosage; see Pemphigus.
• Azathioprine—2 mg/kg PO q48h to twice 
weekly.
• Chlorambucil—2 mg/m2 PO q48h.
• Tetracycline—250 mg <10 kg, 500 mg 
>10 kg PO q8–12h.
• Doxycycline—10 mg/kg PO q24h.
• Minocycline—5 mg/kg PO q12h with 
niacinamide: 250 mg <10 kg, 500 mg >10 kg 
PO q8–12h.
• Cyclosporine, modified—5 mg/kg PO q24h.
• Dapsone—1 mg/kg PO q8h until remission; 
tapered to 1 mg/kg q24h or twice weekly.• Sulfasalazine—10–20 mg/kg PO q8h until 
remission; then as needed.
• Prednisolone—2.2–4.4 mg/kg PO q24h until 
remission; taper to alternate-day therapy.
• Dapsone—1 mg/kg PO q8h until 
remission; taper and give as needed.
Prednisolone—2.2–4.4 mg/kg PO q24h until 
remission; then as needed to prevent relapses 
(usually long-term, alternate-day therapy 
required).
Prednisolone
• Iatrogenic Cushing’s syndrome.
• Muscle wasting.
• Steroid hepatopathy.
• Polydipsia, polyuria.
• Polyphagia.
Dapsone
• Dogs—mild anemia, mild leukopenia, and 
mild elevation of alanine aminotransferase 
(ALT), not associated with clinical signs; 
usually return to normal when dosage is 
reduced for maintenance.
• Rare fatal thrombocytopenia or severe 
• Occasional vomiting, diarrhea, or pruritic 
skin eruption.
• Cats—more susceptible to dapsone toxicity; 
hemolytic anemia and neurotoxicity reported.
Sulfasalazine
Keratoconjunctivitis sicca.
Azathioprine and Chlorambucil
Potential for bone marrow suppression, 
gastrointestinal upset; azathioprine can cause 
hepatotoxicity and possibly pancreatitis.
Cyclosporine
May cause vomiting and diarrhea, gingival 
hyperplasia, B-lymphocyte hyperplasia, hirsutism, 
papillomatous skin eruptions, and increased 
incidence of infection; decreased glucose 
homeostasis; potential toxic reactions rare and 
include nephrotoxicity and hepatotoxicity.
N/A
N/A
  FOLLOW-UP
• Dapsone—monitor hemogram, platelet 
count, and ALT every 2 weeks initially and if 
any clinical side effects develop.• Long-term sulfasalazine therapy—monitor 
tear production.
• Immunosuppressive therapy—monitor 
every 1–2 weeks initially; then every 3–4 
months during maintenance therapy.
N/A
Dermatophytosis: may infect human beings 
in the household.
N/A
SEE ALSO
Companion: Small Animal Dermatology,  
number="3">3rd ed. Hoboken, NJ: 
Nuttall T, Eisenschenk M, Heinrich NA, 
Harvey RG. Skin Diseases of the Dog and 
Cat, 3rd ed. London: CRC Press, 2018.
available onlineDermatoses, Vesiculopustular  (continued)

Canine and Feline, Seventh Edition  387
DDermatoses, Viral (Non-Papillomatosis)
  BASICS
OVERVIEW
• Dermatoses caused by viral infection within 
keratinized structures.  • Viral replication may 
cause cytosuppressive effects or upregulate 
keratinization, resulting in hyperplastic or 
crusted conditions.
• Young to young adult dogs.  • Cats of any age.
SIGNS
• Facial involvement or involvement of head 
is common.  • Lesions often asymmetric in 
distribution.  • Paws and/or foot pads may 
be affected as well as mucocutaneous 
junctions.  • Acute or gradual onset; lesions 
may be associated with bite wound or fight.  
• Variable pruritus; can progress to self-  
mutilation. • Crusts.  • Abscess.  
• Paronychia.  • Poor wound healing.
• Seborrhea.  • Exfoliative dermatitis.  
• Cutaneous horns.  • Gingivitis/stomatitis.  
• Cutaneous or oral ulceration.  • Nasodigital 
hyperkeratosis. • Pigmented macules or 
plaques.  • Progression to bowenoid in situ 
carcinoma (feline immunodeficiency virus 
[FIV], papillomavirus).  • Multiple mast cell 
tumors (FIV).  • Systemic signs of illness may 
be present.  • Signs consistent with upper 
respiratory infection may or may not be 
present prior to development of skin lesions.
• Feline leukemia virus (FeLV).  • FIV.  
• Feline cowpox virus infection.  • Feline 
infectious peritonitis.  • Feline papillomavirus.  
• Canine papillomavirus.  • Canine distem-
per. • Contagious viral pustular dermatitis 
(orf [parapoxvirus]).  • Pseudorabies 
(α-herpesvirus).  • Feline rhinotracheitis 
infection ( α-herpesvirus-1).  • Feline 
calicivirus infection.  • Fighting or hunting 
behavior, multiple animal households, 
exposure to infected animals, and/or ingestion 
of infected material increases risk of exposure.
  DIAGNOSIS
• Crusting diseases—drug eruption, actinic 
keratoses, pemphigus foliaceus, systemic 
lupus erythematosus, other causes for 
exfoliative dermatitis.  • Allergic disorders—
usually pruritic: atopy, fleas, food.  • Feline 
herpesvirus dermatitis lesions can mimic 
lesions of eosinophilic granuloma complex.  
• Parasitic diseases—canine and/or feline 
scabies, demodicosis, cheyletiellosis.  
• Infectious diseases—superficial and deep 
bacterial and fungal infections, leishmaniasis.• Dogs—zinc deficiency syndromes, 
hepatocutaneous syndrome, nasal hyper -
keratosis.  • Neoplasia—with extensive 
crusting and ulceration; squamous cell 
carcinoma, mast cell tumor, epitheliotropic 
lymphoma.
Nonspecific
• Skin biopsy—necessary to prove viral origin 
of skin lesions; not always conclusive; if 
considering herpesvirus dermatitis, inform 
pathologist of suspicion. •  Virus isolation. 
• Serology—confirms FeLV, FIV, or other 
viral infection.
• Skin scrapings, trichograms—parasitic 
infestations. •  Dermatophyte culture—fungal 
infections. •  Epidermal cytology—bacterial 
folliculitis. •  Skin biopsy is definitive 
diagnostic test. •  Immunohistochemical 
staining for viral particles. •  Viral serology 
and/or PCR.
• Irregular hyperplasia. •  Ballooning 
degeneration. •  Hydropic interface dermati-
tis. • Syncytial-type giant cell formation 
within epidermis and/or outer root sheath of 
hair follicle with associated apoptotic 
keratinocytes. •  Keratinocyte inclusion 
bodies. •  Epidermal ulceration with dermal 
necrosis, necrosis of epitrichial sweat glands, 
neutrophilic and/or eosinophilic 
  TREATMENT
• Usually outpatient, except for systemically 
ill patients.  • Prevent exposure to other 
animals that could become infected.
• Supportive care and treatment of 
secondary infections.  • Cats—herpesvirus: 
L-lysine 200–500 mg/cat q12h (questionable 
efficacy); interferon- α 30 units/cat/day PO; 
famcyclovir 125 mg q12h or 40–90mg/kg 
q12h, use of topical acyclovir reported.  
• Cats—bowenoid in situ carcinoma: 
imiquimod. •  Dogs—individual papillomas: 
surgical excision; imiquimod.
Immunosuppressive therapies.  FOLLOW-UP
Varies based on viral infection and presence 
or absence of systemic involvement.
Prevent hunting behavior and exposure to 
potentially infectious materials and infected 
animals.
• Skin lesions may not respond to therapy. 
• Systemic signs may eventually develop as 
result of viral infection. •  Dependent on 
causal virus, animals may self-cure. •  In cats, 
papillomavirus infection may progress to 
bowenoid in situ carcinoma.
Dependent on viral cause.
Feline cowpox virus and contagious viral 
pustular dermatitis (parapoxvirus) can be 
transmitted to other dogs, humans, and 
cats.
SEE ALSO
• Canine Distemper.
Infection.
Author  Elizabeth R. Drake
Resnick

388  Blackwell’s Five-Minute Veterinary Consult  
DDestructive and Scratching Behavior—Cats
  BASICS
OVERVIEW
• Behavior that causes damage to an owner’s 
home or belongings. •  Primary destructive 
behaviors are normal feline behaviors that occur 
during exploration and play; scratching may be 
part of normal nail maintenance and communi -
cation with visual and scent marks. •  Secondary 
destructive behavior may be a sign of other 
behavioral conditions and disease states.
• Gastrointestinal—damage to teeth; 
vomiting, diarrhea, obstruction if items 
ingested.
• Ingestion of toxic material could affect any 
organ system.
• Any breed or gender; may be genetic basis 
for sucking or chewing fabric in Siamese, 
Burmese, and Birman. •  Primary destructive 
behavior is more common in young cats.
SIGNS
Primary Destructive Behavior
• No specific environmental trigger. 
• Common targets for scratching are 
furniture, door frames, carpet, speakers. 
• Curtains and furniture may be damaged 
when cats climb to explore or play. •  May 
chew houseplants. •  Items resembling string, 
including thread, shoelaces, and rubber 
bands, are often chewed and ingested; small 
items that are batted about may be acciden-
tally swallowed.
Secondary Destructive Behavior
• Attention-seeking—destructive behavior in 
presence of owner. •  Separation-related 
distress—destructive behavior in absence of the 
owner. •  Compulsive behavior—licking, 
chewing, sucking, or ingesting nonfood items. 
• Scratching may occur secondary to household 
conflict.
• Lack of suitable outlets for scratching, climbing, 
perching, play, and resting. •  Inadequate 
supervision, particularly in young cats.
  DIAGNOSIS
• Rule out medical conditions, especially if onset 
in mature cat. •  Conditions affecting digestion, 
absorption, and appetite, including recent diet 
change. •  Gastrointestinal disease and medical 
conditions associated with pain or anxiety.CBC/BIOCHEMISTRY/URINALYSIS
As indicated to rule out medical conditions (T4).
IMAGING
As indicated to rule out medical conditions.
For chewing/ingestive behavior, attention to 
oral cavity and scoping if indicated to rule out 
gastrointestinal causes.
  TREATMENT
T reat underlying disease.
• Keep claws trimmed. •  Supervise/confine until 
appropriate behavior patterns have been 
established; provide food, litter, toys, and 
scratching posts in confinement area. •  Prevent 
access to potential targets. •  Provide acceptable 
scratching substrate such as sisal, cardboard, and 
loosely woven carpet in locations and orientation 
(horizontal or vertical) based on cat’s preference. 
• Apply feline interdigital pheromone to 
scratching posts. •  Provide climbing towers, 
interactive play, feeding stations at different levels, 
food-dispensing toys, and multiple small meals. 
• Reward appropriate behavior. •  Reduce appeal 
of target areas and objects—e.g., double-sided 
sticky tape. •  Provide indoor grass gardens. 
• Declawing is banned in a number of countries 
and jurisdictions for ethical and humane reasons; 
where still legally permissible it should be a last 
resort after owners have been counseled on all 
alternative options. •  While behavior modifica -
tion is being implemented, plastic claw covers 
may be applied to prevent further damage.
• Attention-seeking behavior—provide 
owner-initiated interactions. •  Separation-
related distress—provide opportunities for 
independent play and exploration. 
• Compulsive disorder—identify and reduce 
sources of anxiety; offer appropriate outlets 
for play, chewing, and food-filled toys; some 
cats will chew rawhide; prevent access to 
target items. •  Reduce household conflict.
• Medication is not indicated for primary 
destructive or attention-seeking behaviors. 
• Medication may be indicated in combina-
tion with behavior management and 
modification for anxiety-based conditions 
and compulsive disorders. •  See Fear, Phobias, and Anxieties—Cats; Compulsive 
Disorders—Cats.
Pheromones and Nutraceuticals
• Feline interdigital pheromone applied to 
scratching posts to encourage scratching. •  F3 facial 
pheromone, cat-appeasing pheromone, alpha- 
casozepine, and l-theanine may reduce anxiety .
  FOLLOW-UP
Weekly follow-up to support owners.
• Destructive behavior is normal and self-reward -
ing. •  Frequency may be reduced through client 
education during the first well-care visit, 
regardless of the age of the patient. •  Provide 
information on suitable outlets for scratching, 
chewing, exploration, play, and enrichment.
• Owners become frustrated, resulting in 
declawing or relinquishment. •  Punishment can 
trigger fear or aggression. •  Obstruction due to 
foreign body, including string foreign body.
• Resolution of normal exploratory behavior 
usually within weeks. •  Anxiety-based 
conditions and compulsive disorders often 
require long-term management, including 
psychotropic medication.
Rule out medical conditions in adult onset.
Preparturient destructive behavior (nesting).
SEE ALSO
• Fears, Phobias, and Anxieties—Cats. 
• https://fearfreehappyhomes.com/category/
explore/exercise-enrichment •  https://catvets.
com/guidelines/practice-guidelines/
environmental- needs-guidelines •  https://
indoorpet.osu.edu/cats
Heath S. Canine and feline enrichment in the home 
and kennel: a guide for practitioners. Vet Clin 
North Am Small Anim Pract 2014, 44:427–449.
ed. Philadelphia, PA: Elsevier Saunders, 2013.
Author  Ellen M. Lindell

Canine and Feline, Seventh Edition  389
DDestructive Behavior—Dogs
  BASICS
home, property, or belongings.
• Primary destructive behavior is normal 
behavior that includes exploratory and play- 
based behavior.
• Secondary destructive behavior is a clinical 
sign of another behavior condition.
• Dogs normally explore and engage with 
their environment. When access to appropri -
ate outlets and enrichment is not readily 
available and in the absence of supervision and 
guidance, owner’s property may be targeted.
• Insufficient opportunities for social 
interactions can contribute to destructive 
behavior.
• Dogs may dig for comfort or cooling, and 
to escape confinement. Digging can be 
triggered by sounds of burrowed animals and 
scents of food sources.
• Though manipulating the environment 
results in property damage, it may be self- 
rewarding and self-soothing.
• Conditions causing distress, including pain, 
fear, anxiety, and frustration, can contribute 
to destructive behavior.
• Behavioral—frustration or anxiety.
• Gastrointestinal (GI)—damage to teeth or 
oral mucosa; pharyngitis or esophagitis; 
vomiting, diarrhea, or obstruction if ingested.
• Musculoskeletal—trauma caused by 
scratching, chewing, or digging.
• Skin—excoriation, nail damage secondary 
to trauma.
GENETICS
None
Normal canine behavior—problem reported 
by approximately 12% of owners.
None
• Breed predilections—certain breeds are by 
nature more active and, if insufficient outlets 
for exploratory and/or social engagement, 
may engage in destructive behavior. Northern 
breeds may dig for resting and thermoregula-
tion. Some terrier and hound breeds may dig 
when burrowing for prey.
• Mean age and range—primary destructive 
behavior most often seen in puppies and 
young dogs; secondary destructive behavior 
seen at any age.
• Predominant sex—N/A.SIGNS
• Destructive behavior is a clinical sign rather 
than a diagnosis.
• Dogs may use their teeth or claws to damage 
floors, furniture, walls, or frames of doors and 
windows or dig at fencing. Some dogs chew or 
even ingest small personal items.
• Clients may ascribe the underlying motiv  - 
ation to spite or suggest a diagnosis such as 
separation anxiety. Though barriers are often 
targeted in association with separation-related 
distress or territorial behavior, no focus of 
damage is pathognomonic.
• Knowledge of the contexts in which 
destructive behavior occurs is critical for 
• Physical examination findings—fractured 
teeth; excoriations on nose; broken front 
claws; digital pain.
CAUSES
• Primary destructive behavior:
◦ Inadequate supervision provides access to 
self-rewarding behavior.
◦ Lack of access to preferred chewable and/
or interactive toys.
◦ Insufficient cognitive enrichment.
◦ Inadequate social enrichment.
• Secondary destructive behavior:
◦ Confinement in presence of an inciting 
trigger.
◦ Confinement frustration.
◦ Separation-related distress—inadequate 
habituation to absence of owner.
◦ Noise phobia.
◦ Territorial behavior.
◦ Unintentional reinforcement by owner.
◦ Medical conditions associated with pain.
 RISK FACTORS
Early environmental experiences including prior 
emotional trauma are risk factors for develop -
ment of fear and anxiety-related conditions.
  DIAGNOSIS
• Pathologic conditions—index of suspicion 
for underlying medical condition should be 
high in adult patients with sudden onset of 
destructive behavior in absence of notable 
environmental changes.
• GI disease—if pica accompanies destructive 
chewing: rule out conditions affecting 
digestion, absorption, and polyphagia, 
including recent diet changes that can affect 
satiety; licking of surfaces such as floors, 
carpet, and nonfood items may be associated 
with upper GI disease.
• Separation-related distress.
• Noise phobia, storm phobia—distress in 
response to stimulus.
• Territorial behavior—destructive behavior 
related to presence of triggers; window frames 
and doorways are damaged.• Cognitive dysfunction syndrome—
destructive behavior related to agitation, 
anxiety, and abnormal repetitive behaviors 
with onset or progression in patients 7 years 
or older; other signs of cognitive dysfunction 
are typically present.
No pathology expected.
N/A except lesions secondary to self-trauma.
  TREATMENT
• T raumatic injuries are typically minor and 
can be managed with outpatient care. 
T raumatic dental injuries and GI foreign 
bodies may require surgical intervention.
• Behavioral treatment protocols include 
behavior modification to address frustration 
or anxiety; determination of safe methods for 
supervision, confinement; and customized 
enrichment protocol based on patient 
preferences and owner lifestyle.
• All toys carry a potential risk of injury to 
the patient, including inadvertent ingestion 
and dental injury.
• Environmental management:
◦ Prevent or supervise access to potential 
targets of destruction.
◦ Provide thermoregulation options (kiddie 
pool, dog house) to reduce digging.
• Behavior modification may include:
◦ Providing for and reinforcing alternative 
desirable activities and outlets.
◦ Relaxation exercises to reduce inadvertent 
reinforcement of undesirable behavior.
◦ Habituation to crate or gate confinement.
• Environmental enrichment:
◦ Preference testing of appropriate toys and 
chew items.
◦ Provide acceptable substrate and location 
for digging—treats and toys can be buried 
to encourage digging in area.
• Design a schedule for provision of exercise, 
cognitive enrichment, social enrichment, and 
reward-based training.
• Design a behavioral log to record progress 
and preferences.
Behavioral appointments can be scheduled 
with veterinarian or trained nursing staff.
ACTIVITY
• Aerobic exercise schedule should consider 
the patient’s physical health. Healthy dogs 
may benefit from two half-hour exercise 
sessions each day.

390  Blackwell’s Five-Minute Veterinary Consult  
D• Cognitive stimulation may be provided 
with reward-based training and food 
puzzles.
• Provide opportunities for dogs to engage 
in breed-typical normal behaviors, including 
sniffing and “hunting” (tracking, nosework).
DIET
• Some patients benefit from feeding via 
puzzles and food-stuffed toys.
• Food toys may not be appropriate for pets 
that exhibit possessive or food-related 
• Clients should take an active role in 
managing destructive behavior.
• Preadoption counseling provides an 
opportunity to educate clients regarding 
providing for pets’ needs, including social 
and exploratory play and safe toys.
• Provide a plan for supervision and 
enrichment.
• Teach clients to communicate expectations 
by reinforcing desired behaviors and 
preventing access to undesirable behaviors, 
including dog proofing and confinement 
training.
• Provide references for local trainers who 
support positive reinforcement rather than 
confrontation.
Aversive Products and Punishment
• Application of nontoxic bitter-tasting 
products to targeted objects is sometimes 
used to manage primary destructive behavior 
in conjunction with supervision.
• It is essential that, upon discovering an 
unpleasant taste, the dog has immediate 
access to an appropriate item; it is more 
effective and appropriate to supervise and 
quietly guide dogs toward appropriate items.
• Punishment is not an accepted tool for 
managing destructive behavior; it does not 
address the underlying motivation and can 
lead to fear, anxiety, or aggression.
N/A
• Medication is not indicated for treating 
primary destructive behaviors or attention-
seeking behavior.• Medication complements behavior 
modification and may provide more rapid 
resolution when treating anxiety-based 
(SSRIs)
Fluoxetine—0.5–2 mg/kg PO q24h.
Clomipramine—1–3 mg/kg PO q12h.
For Situational Anxiety (Alone or 
Together with SSRI or TCA)
• Alprazolam—0.01–0.1 mg/kg PO prior to 
event.
• T razodone—3–10 mg/kg PO prior to event.
• Clonidine—0.01–0.05 mg/kg PO prior to 
event.
TCAs—contraindicated in animals with 
cardiac conduction disturbances or glaucoma.
Benzodiazepines may disinhibit aggression—
use with caution in dogs with a history of 
• SSRIs, TCAs, and trazodone should not be 
used with monoamine oxidase inhibitors, 
including amitraz and selegiline.
• Combining drugs that increase serotonin 
(e.g., SSRI or TCA with trazodone) should be 
done with caution to avoid serotonin 
syndrome.
Dog-appeasing pheromone, nutraceuticals 
containing L-theanine or alpha-casozepine, or 
a calming probiotic may be used to reduce 
mild anxiety. The safety margin is wide.
  FOLLOW-UP
Weekly calls to confirm compliance and 
adjust enrichment based on patient prefer-
ences. Most patients benefit from one-on-one 
behavior modification sessions every 2 weeks.
Client education during the first visit, 
regardless of the age of the patient. Provide 
information on suitable outlets for chewing, 
digging, exercise, reward training, and the 
importance of both cognitive and social 
enrichment.POSSIBLE COMPLICATIONS
Without adequate support, owners may 
become frustrated, resulting in relinquish-
ment of the dog. Owners may seek advice 
from individuals offering “quick fixes” that 
could ultimately jeopardize the patient.
 EXPECTED COURSE AND PROGNOSIS
Prognosis is excellent. Resolution of normal 
exploratory behavior is usually rapid.
Destructive behavior is often associated with 
attention-seeking behavior.
Young dogs are at increased risk for normal 
destructive behavior.
None
SEE ALSO
• Cognitive Dysfunction Syndrome.
• Marking, Roaming, and Mounting 
Behavior—Dogs.
• Puppy Behavior Problems.
• Separation Anxiety Syndrome.
• Thunderstorm and Noise Phobias.
• Unruly Behaviors: Jumping, Pulling, 
Chasing, Stealing—Dogs.
• fearfreehappyhomes.com
• https://indoorpet.osu.edu/dogs/
environmental_enrichment_dogs
Heath S. Canine and feline enrichment in the 
home and kennel: a guide for practitioners. 
Vet Clin North Am Small Anim Pract 2014, 
44:427–449.
2018, pp. 745–753, 767–773.
Consulting Editor  Gary M. LandsbergDestructive Behavior—Dogs  (continued)

Canine and Feline, Seventh Edition  391
DDiabetes Insipidus
  BASICS
Diabetes insipidus (DI) is a disorder of water 
metabolism characterized by polyuria (PU), 
urine of low specific gravity or osmolality 
(so-called insipid, or tasteless, urine), and 
polydipsia (PD).
• Central DI (CDI)—deficiency in the 
secretion of antidiuretic hormone (ADH).
• Nephrogenic DI (NDI)—renal insensitivity 
to ADH.
• Primary CDI—rare.
• Primary NDI—rare.
Species
None
• Congenital forms <1 year.
• Acquired forms, any age.
SIGNS
• PU.
• PD.
• Incontinence—occasional.
• Signs of intracranial mass if due to pituitary 
tumor.
• Dehydration and weakness in animals with 
uncompensated free water loss.
CAUSES
Inadequate Secretion of ADH
• Congenital defect.
• T rauma.
Renal Insensitivity to ADH
• Congenital—defect in aquaporin (renal 
tubular channel that allows free water 
reabsorption).
• Secondary to drugs (e.g., lithium, 
demeclocycline).
• Secondary to endocrine and metabolic 
disorders (e.g., hyperadrenocorticism, 
hyponatremia, hypercalcemia).
• Secondary to renal disease or infection (e.g., 
pyelonephritis, chronic kidney disease, 
pyometra).  DIAGNOSIS
Polyuric Disorders
• Renal disease.
• Hyperthyroidism—cats.
• Liver disease—portosystemic shunt.
• Hypercalcemia.
• Primary PD.
• Usually normal; hypernatremia in patients 
with excessive free water loss.
• Urinary specific gravity low ( <1.006, 
hyposthenuria).
Plasma ADH (not commercially available).
IMAGING
• MRI or CT scan if pituitary tumor is 
• Abdominal radiographs or ultrasound may 
help rule out other polyuric disorders.
• ADH supplementation trial—preferred to 
water deprivation test; therapeutic trial with 
synthetic ADH (desmopressin [DDAVP]); 
positive response (water intake decreases by 
50% in 5–7 days).
• Modified water deprivation test (see 
Appendix II for protocol)—not routinely 
recommended due to risk of complications.
• Rule out all other causes of PU/PD before 
considering primary CDI.
Degeneration and death of neurosecretory 
neurons in neurohypophysis (primary CDI).
  TREATMENT
• Patients should be hospitalized for modified 
water deprivation test; the ADH trial is often 
performed as an outpatient procedure.
• Animals with NDI should have underlying 
disease diagnosed and treated.
ACTIVITY
Not restricted.
DIET
Normal, with free access to water.
• Review dosage of DDAVP and admini -
stration technique.
• Importance of having water available at all 
times.SURGICAL CONSIDERATIONS
Pyometra is a surgical emergency and should 
be removed as soon as the patient is 
• CDI—DDAVP (1–2 drops of intranasal 
preparation in conjunctival sac q12–24h to 
control PU/PD); alternatively, intranasal 
preparation may be given SC (2–5  μg, 
q12–24h). Oral preparation of DDAVP is 
available in 0.1–0.2 mg tablets, with each 
0.1 mg comparable to 1 large drop of 
intranasal preparation.
• NDI—hydrochlorothiazide (2–4 mg/kg 
PO q12h), in addition to treatment of any 
None
Overdose of DDAVP can cause water 
intoxication.
  FOLLOW-UP
• Adjust treatment according to patient’s 
signs; ideal dosage and frequency of DDAVP 
administration based on water intake.
• Laboratory tests such as PCV, total solids, 
and serum sodium concentration, and patient 
weight to detect dehydration (inadequate 
DDAVP replacement).
Circumstances that might increase water loss.
Anticipate complications of primary disease 
(e.g., pituitary tumor).
• CDI usually permanent, except in patients 
in which condition was trauma induced.
• NDI usually resolves with treatment of 
• Prognosis generally good, depending on 
• Without treatment, dehydration can lead to 
stupor, coma, and death.
• Congenital CDI and NDI usually manifest 
before 6 months of age.
• CDI related to pituitary tumors usually 
seen in dogs >5 years old.

392  Blackwell’s Five-Minute Veterinary Consult  
DSYNONYMS
• Cranial diabetes insipidus.
• ADH-responsive diabetes insipidus.
SEE ALSO
Hyposthenuria
• ADH = antidiuretic hormone.
• CDI = central diabetes insipidus.• DI = diabetes insipidus.
• NDI = nephrogenic diabetes insipidus.
• PD = polydipsia.
• PU = polyuria.
Feldman EC, Nelson RW, Reusch CE, 
Scott-Moncrieff JCR. Canine and Feline 
Endocrinology, 4th ed. Philadelphia, PA: 
Saunders, 2015.Author  Patty A. Lathan
of Rhett Nichols.
available onlineDiabetes Insipidus  (continued)

Canine and Feline, Seventh Edition  393
DDiabetes Mellitus With Hyperosmolar Hyperglycemic State
  BASICS
• The hyperosmolar hyperglycemic state 
(HHS) is a complicated form of diabetes 
mellitus (DM) characterized by severe hyper-  
glycemia and dehydration that produces a 
marked elevation in serum osmolarity. Unlike 
diabetic ketoacidosis (DKA), ketone production 
and metabolic acidosis are not major features of 
HHS. • Specific guidelines for HHS diagnosis 
are lacking in dogs and cats, but serum effective 
osmolarity >320 mOsm/L, glucose 
concentration >600 mg/dL, and bicarbonate 
concentration >18 mEq/L, along with minimal 
ketonuria, are criteria in humans.
• Hyperglycemia is due to insulin deficiency 
from DM; insulinopenia reduces tissue glucose 
utilization and increases hepatic glucose 
production, leading to increased extracellular 
glucose concentrations; the magnitude of 
hyperglycemia in HHS is usually greater than 
in DKA. • Hyperosmolarity develops 
secondary to hyperglycemia and is exacerbated 
by dehydration and reduced extracellular fluid 
volume; the contribution of glucose to total 
plasma osmolarity is significant in HHS. 
• Dehydration and volume deficit are typically 
severe and are caused by several factors, 
including reduced water intake and volume 
losses via gastrointestinal and renal systems. 
• Reduced plasma volume decreases 
glomerular filtration rate and urine 
production, leading to azotemia; in HHS, 
severe volume contraction with reduced 
urinary glucose excretion results in severe 
hyperglycemia and plasma hyperosmolarity. 
• Hyperketonemia and ketonuria are not 
major features of HHS; lactic acidosis 
secondary to volume depletion, tissue 
hypoperfusion, and impaired glucose 
metabolism is the major cause of acidosis in 
patients with HHS.
• Endocrine. • Renal/urologic—prerenal 
azotemia due to decreased extracellular fluid 
volume; urine production usually maintained 
by glucose-induced diuresis unless volume 
deficit is severe or acute kidney injury is 
present. • Cardiovascular—hypovolemia; 
metabolic acidosis and electrolyte abnormalities 
may contribute to hypotension and poor 
myocardial contractility. • Nervous—
hyperosmolarity promotes intracellular 
dehydration and neuronal dysfunction.
GENETICS
N/A
Uncommon
Species
Dog and cat (more frequent).
N/A
Most common in middle-aged dogs (mean 9 
years) and cats (mean 12 years).
N/A
SIGNS
• All patients have DM; in some, diagnosis of 
DM occurs prior to HHS. • Some patients 
have concurrent chronic illness. • Signs 
caused by DM—may not be appreciated after 
HHS onset: ◦ Polydipsia. ◦ Polyuria. 
◦ Polyphagia. ◦ Weight loss. • Signs caused 
by HHS: ◦ Weakness/lethargy. ◦ Vomiting. 
◦ Reduced appetite. ◦ Neurologic complaints—  
abnormal responsiveness, coma.
• Findings associated with dehydration and 
hypovolemia: ◦ Decreased skin turgor. 
◦ Prolonged capillary refill time. ◦ Reduced 
pulse pressure. ◦ Tachycardia. ◦ Hypothermia. 
• Findings associated with hyperosmolarity: 
◦ Lethargy, depressed mentation, stupor, or 
coma. ◦ Seizure. • Findings associated with DM: 
◦ Low body condition score. ◦ Cataracts (dogs).
CAUSES
• Develops in patients with DM and severe 
dehydration/volume loss. • Reduced water 
intake may precede onset of HHS. 
• Comorbid conditions common.
Risk for HHS may be higher in diabetic 
animals with concurrent disorders, including 
heart disease, renal insufficiency, hyperadren-
ocorticism, acute pancreatitis, and neoplasia.
  DIAGNOSIS
• DM—may be uncomplicated to complicated, 
including DKA and HHS; all have similar 
clinical signs and laboratory findings, but can 
be subcategorized based on magnitude of 
hyperglycemia and hyperketonemia. 
• Hypernatremia—severe hypernatremia 
produces CNS signs similar to HHS, but 
with sodium as major osmole; polyuria and 
polydipsia may be present, particularly if 
hypernatremia develops secondary to diabetes 
insipidus. • Hyperosmolarity of any cause— 
may produce similar CNS abnormalities; toxins 
(e.g., ethylene glycol or alcohol) or CNS 
lesions (e.g., causing adipsia) may cause 
hyperosmolarity. • CNS disease—primary 
CNS disorders may produce clinical signs of 
HHS; marked fluid deficits are not expected. • Myxedema coma—manifestation of severe 
hypothyroidism with similar clinical signs 
without hyperosmolarity or hyperglycemia; 
low total thyroxine and elevated thyroid-
stimulating hormone present.
• Hyperglycemia—blood glucose concen -
tration frequently exceeds 600 mg/dL and 
severe hyperglycemia (1500–2000+ mg/dL) 
exists in some patients. • Azotemia—elevated 
blood urea nitrogen (BUN) and serum 
creatinine concentrations are common, usually 
prerenal, but renal azotemia occurs in some 
patients. • Sodium—hypo- or hypernatremia 
may be observed; hyperosmolarity is most 
severe with concurrent hyperglycemia and 
hypernatremia. • Potassium—hypokalemia is 
common; hyperkalemia is associated with 
acute kidney injury or reduced urine output. 
• Acidosis—metabolic acidosis is less severe 
than DKA; hypobicarbonemia and 
hyperlactatemia occur secondary to 
hypovolemia or renal failure. • Glucosuria—
present; mild ketonuria possible. • Urine 
specific gravity (USG) variable; may be 
misleading due to glucosuria, which increases 
USG.
• Blood and urine osmolarity—serum 
osmolarity >320 mosm/L consistent with 
HHS; urine osmolality elevated due to 
glucosuria. • Serum osmolarity can be 
estimated from routine serum chemistry results: 
2 ([Na+]+[K+]) + [BUN]/2.8 + [Glucose]/18; if 
results are in IU, equation is modified: 2 
([Na+]+[K+]) + [BUN] + [Glucose].
IMAGING
N/A
N/A
• Pancreas—consistent with DM: islet 
atrophy and loss (dogs and cats) and islet 
amyloid (cats). • Brain—changes not specific 
for HHS; evidence of CNS edema.
  TREATMENT
Life-threatening medical emergency 
requiring inpatient treatment. After HHS 
resolution, patients require treatment and 
follow-up for DM.
• Correction of fluid deficits—major 
treatment goal, begin prior to insulin 
replacement; IV fluid replacement indicated 
for ill patients; enteral water can assist with free 
water replacement in patients that tolerate oral 
intake. • Fluid type and rate depend on 
patient’s hydration and volume status and 
magnitude of metabolic derangements; fluid

394  Blackwell’s Five-Minute Veterinary Consult  
Ddeficit is estimated using the equation: 
%volume depletion * body weight(kg) = fluid 
deficit (L). • Hypo- and normonatremic 
patients—isotonic crystalloid solution is 
appropriate for initial volume replacement; 
replacement of volume deficit should occur 
over 12–24h; patients with hypotension or 
shock due to hypovolemia should receive fluid 
bolus of 20–25% of estimated blood volume 
(dog: 80 mL/kg; cat: 50 ml/kg), which can be 
repeated until blood pressure is adequate; once 
blood pressure is restored, the remaining deficit 
is replaced over 12–24h. • Hypernatremic 
patients—hypernatremia implies a free water 
deficit and its occurrence with hyperglycemia 
in HHS may result in life-threatening 
hyper  osmolarity; isotonic (0.9%) saline 
solution appropriate for initial volume 
replacement in hypernatremic patients with 
hypovolemic hypotension; if hypernatremia 
persists after blood pressure and urine output 
are restored, use of hypotonic (0.45%) saline 
solution indicated to replace free water and 
reduce sodium, unless oral water intake 
possible; recommended that serum sodium 
concentration reduction should not exceed 
12 mEq/day (see Hypernatremia). • Electrolyte  
replacement—potassium deficiency is 
expected, and should be replaced unless 
hyperkalemia is present; dosage based on 
magnitude of hypokalemia; potassium 
replacement by IV infusion should not exceed 
0.5 mEq K+/kg/h and fluids with supplemented 
K+ should be avoided during rapid volume 
infusion; supplementation of other electrolytes 
(e.g., magnesium, phosphorous) may also be 
necessary. • Glucose supplementation—some 
protocols recommend using dextrose infusion 
to prevent hypoglycemia during insulin 
therapy; 2.5–5% dextrose CRI used as needed 
to maintain blood glucose concentrations 
between 150 and 250 mg/dL.
ACTIVITY
N/A
DIET
N/A
• Patients frequently have a serious concurrent 
disorder(s) that affects prognosis. • Permanent 
DM is expected and survivors will require 
lifelong treatment for DM.
N/A
• CRI of regular insulin is recommended for 
initial glucose control; insulin therapy should 
be started 2–6h after starting fluid therapy so 
initial decrease in serum glucose is not extreme. 
• CRI preparation—regular insulin at 2.2 U/kg/24h (some protocols recommend 1.1 U/
kg/24h dose in cats) added to 250 mL of 0.9% 
NaCl; prior to beginning CRI, 50 mL of 
solution should pass through plastic 
administration tubing and be discarded 
(insulin binds to some plastics); CRI started at 
5 mL/h (cat) or 10 mL/h (dog) and infusion 
rate adjusted as needed to reduce hyperglycemia 
at desired rate and maintain target glucose 
concentration. • Once HHS is resolved and 
patient stable, discontinue insulin CRI and 
transition to longer-acting insulin to be used 
for chronic DM management.
N/A
• Brain edema may occur when hyperosmolarity 
is corrected too rapidly; patients with edema 
develop worsening neurologic status during 
treatment; minimizing rapid decreases in glucose 
and sodium during treatment lowers edema risk. 
• Insulin administration can result in hypokalemia; 
electrolytes should be monitored frequently 
(q4–6h) until stable.
N/A
• Ultrashort-acting insulins (insulin aspart or 
insulin lispro) may be substituted for regular 
insulin in CRI protocols. • Protocol for 
intermittent IM use of regular insulin (when 
CRI not available)—0.2 U/kg IM initially, 
followed by 0.1 U/kg IM q1h until glucose 
<250 mg/dL; subsequent doses 0.5–1.0 U/kg 
IM q4–6h to maintain glucose concentration 
  FOLLOW-UP
• Volume and hydration status—monitor 
heart rate, pulse quality, capillary refill time, 
blood pressure, bodyweight, and urine 
output. • Blood glucose—monitor q1–2h to 
guide insulin therapy; aim for gradual 
reduction of serum glucose (50–100 mg/
dL/h) to 150–250 mg/dL without hypo -
glycemia. • Monitor serum Na+ and K+ 
concentrations, especially during correction 
of hypernatremia or K+ supplementation; 
magnesium and phosphorous should be 
monitored, especially after start of insulin 
therapy. • After stabilization, long-term 
monitoring appropriate for DM is indicated.
• Adequate insulin therapy and monitoring 
of glycemia in patients with DM may reduce 
risk of HHS. • Early recognition and 
effective treatment of new-onset DM may 
reduce risk of DKA or HHS.POSSIBLE COMPLICATIONS
• Hypoglycemia or electrolyte disturbances 
may develop during treatment. • Severe 
neurologic signs, including coma and death, 
may occur. • Dehydration and shock can 
precipitate acute kidney injury. • Death due to 
shock or coma may occur in untreated animals.
• Hydration and blood pressure should improve 
within a few hours of initiating fluid therapy and 
resolve over 12–24h; hyperglycemia is corrected 
over 6–12h once insulin therapy started. 
• Electrolyte derangements must be managed to 
avoid osmotic complications secondary to 
sodium fluctuations, and to avoid hypo-/
hyperkalemia, hypophosphatemia, or hypo -
magnesemia. • Depending on patient response, 
prognosis is guarded; worse if severe neurologic 
compromise or renal failure is present.
• DKA and HHS have significant overlap in 
clinical signs and laboratory abnormalities. 
• Patients with HHS should be evaluated for 
concurrent conditions (cardiac or renal 
failure, pancreatitis, neoplasia, etc.).
SYNONYMS
• Diabetic coma. • Hyperosmolar nonketotic 
syndrome.
SEE ALSO
• Diabetes Mellitus With Ketoacidosis. 
• Diabetes Mellitus Without Complication—
Cats. • Diabetes Mellitus Without 
Complication—Dogs. • Hyperglycemia. 
• Hyperosmolarity.
• BUN = blood urea nitrogen. • DKA = 
diabetic ketoacidosis. • DM = diabetes mellitus. 
• HHS = hyperosmolar hyperglycemic state. 
Koenig A, Drobatz KJ, Beale AB, King LG. 
Hyperglycemic, hyperosmolar syndrome in 
feline diabetics: 17 cases (1995–2001). J Vet 
Emerg Crit Care 2004, 14:30–40.
O’Brien MA. Diabetic emergencies in small 
animals. Vet Clin North Am Small Anim 
Pract 2010, 40:317–333.
Rand JS. Diabetic ketoacidosis and hyperos-
mola hyperglycemia in cats. Vet Clin North 
Am Small Anim Pract 2013, 43:367–379.
T rotman, TK, Drobatz KJ, Hess RS. 
Retrospective evaluation of hyperosmolar 
hyperglycemia in 66 dogs (1993–2008). J 
Vet Emerg Crit Care 2013, 23:557–564.
Author  Thomas Schermerhorn
Deborah S. Greco.Diabetes Mellitus With Hyperosmolar Hyperglycemic State  (continued)

Canine and Feline, Seventh Edition  395
D
Diabetes Mellitus With Ketoacidosis
  BASICS
A medical emergency secondary to absolute or 
relative insulin deficiency, characterized by 
hyperglycemia, ketonemia, metabolic acidosis, 
dehydration, and electrolyte depletion.
• Insulin deficiency causes an increase in 
lipolysis, resulting in excessive ketone body 
production and metabolic acidosis; an inability 
to maintain fluid and electrolyte homeostasis 
causes dehydration, prerenal azotemia, 
electrolyte disorders, obtundation, and death.
• Many patients with diabetic ketoacidosis 
(DKA) have underlying conditions such as 
infection, inflammation, or heart disease that 
cause stress hormone (e.g., glucagon, cortisol, 
growth hormone, epinephrine) secretion; this 
probably contributes to development of insulin 
resistance and DKA by promoting lipolysis, 
ketogenesis, gluconeogenesis, and glycogenolysis.
• Dehydration and electrolyte abnormalities 
result from osmotic diuresis, promoting the 
loss of total body water and electrolytes.
• Hematologic (cats).
GENETICS
None
Unknown
None
Species
• Dog—miniature poodle and dachshund.
• Cat—none.
• Dog—mean age 8.4 years.
• Cat—median age 11 years (range: 1–19 years).
• Dogs—females 1.5 times more prevalent 
than males.
• Cats—males 2 times more prevalent than 
females.
SIGNS
• Shock.
• Polydipsia or adipsia.
• Muscle wasting and weight loss.• Unkempt haircoat.
• Thin body condition.
• Ketone odor on breath.
• Icterus.
• Dandruff.
CAUSES
• Infection (e.g., pyoderma, pneumonia, 
urinary tract infection, prostatis, pyelo­
nephritis, pyometra).
• Concurrent disease (e.g., heart failure, 
pancreatitis, renal insufficiency or failure, 
asthma, neoplasia, acromegaly).
• Estrus.
• Medication noncompliance.
• Stress.
• Surgery.
• Any condition that leads to absolute or 
relative insulin deficiency.
• History of corticosteroid or beta blocker 
  DIAGNOSIS
• Hyperosmolar hyperglycemic state.
• Acute hypoglycemic coma/insulin overdose.
• Uremia/azotemia due to renal disease or 
postrenal obstruction.
• Other cause of metabolic acidosis (e.g., 
lactic acidosis, ethylene glycol intoxication, 
renal tubular acidosis).
• Leukocytosis with mature neutrophilia.
• Hyperglycemia—blood glucose concen­
tration usually >250 mg/dL.
• High liver enzyme activity.
• Hypercholesterolemia and lipemia.
• Hyponatremia.
• Hypomagnesemia.
• High anion gap—anion gap = (sodium + 
potassium) – (chloride + bicarbonate); normal 
is 16 ± 4.
• Glucosuria and ketonuria.
• Variable urinary specific gravity with active 
or inactive sediment.
• Hyperproteinemia.
• Heinz body anemia (cats).
• Metabolic acidosis—HCO3– <15 mEq/L 
(total CO2 estimates HCO3–).
• Hyperosmolarity ( >330 mOsm/kg).
• Bacterial culture of urine and blood.
• Abdominal and thoracic radiography and 
ultrasound may be necessary to identify 
comorbid diseases.• ECG and blood pressure monitoring 
indicated for patients with shock or 
electrolyte abnormalities.
Pancreatic islet cell atrophy.
  TREATMENT
• If the animal is bright, alert, and well hydrated, 
intensive care and IV fluid administration are 
not required; start SC administration of insulin 
(short ­ or intermediate ­acting insulin), offer 
food, and supply constant access to water; 
monitor closely for signs of illness (e.g., anorexia, 
lethargy, vomiting).
• T reatment of animals with DKA that are 
systemically ill requires intensive inpatient 
care; goals are to correct depletion of water 
and electrolytes, reverse ketonemia and 
acidosis, and increase rate of glucose use by 
insulin ­dependent tissues.
• Fluids—necessary to ensure adequate 
cardiac output and tissue perfusion and to 
maintain vascular volume; also reduce blood 
glucose concentration.
• IV administration of isotonic crystalloid 
supplemented with potassium is initial fluid 
of choice; volume and rate determined by 
fluid replacement needs plus maintenance 
requirements; replace over 24–48h.
ACTIVITY
N/A
DIET
Following stabilization, diet should be 
adjusted to account for patient’s diabetes, 
concurrent disease, and body condition. 
High ­fiber diets are not recommended in 
underweight pets.
Serious medical condition requiring lifelong 
insulin administration in most patients. 
Confirm that client is prepared to inject twice 
daily insulin prior to treatment of DKA.
N/A
Insulin
• Regular insulin is the insulin of choice until 
eating; lispro insulin may also be considered.
• Initial dosage—0.2 U/kg IM (or SC if 
hydration normal).
• Subsequent dosage 0.1–0.2 U/kg IM given 
3–6h later—may be given hourly if patient is 
closely monitored; response to previous insulin 
dosage should be considered when calculating

396  Blackwell’s Five-Minute Veterinary Consult  
Dsubsequent dosages; ideally, glucose 
concentration should drop by 50–100 mg/dL/h.
• Regular insulin can also be administered as 
CRI via designated catheter. Dogs: 2.2 units/kg 
in 250 mL of 0.9% NaCl; Cats: 1.1 units/kg in 
250 mL 0.9% NaCl. Then, allow 50 mL of 
dilute insulin to flow through IV tubing and 
discard. If blood glucose >250 mg/dL, 
administer at 10 mL/h; if blood glucose 
200–250 mg/dL, administer at 7 mL/h; if blood 
glucose 150–200 mg/dL, administer at 5 mL/h; 
if blood glucose 100–150 mg/dL, administer at 
5 mL/h and add 2.5% dextrose to IV crystalloid 
fluids; if blood glucose <100 mg/dL, discontinue 
IV insulin infusion and continue 2.5–5% 
dextrose in IV crystalloid infusion.
• Check blood glucose q1–3h using auto  ­ 
mated test strip analyzer (Accu ­Chek® III, 
Alpha T rak® II glucometer), corrected for 
patient’s PCV as indicated.
• Monitor urine or serum ketones daily.
• Administer longer ­acting insulin once 
patient is eating, drinking, and ketosis is 
resolved; the dosage is based on that of 
short ­acting insulin given in hospital.
Potassium Supplementation
• Total body potassium is depleted and 
treatment (e.g., fluids and insulin) will 
further lower serum potassium.
• If possible, check potassium concentration 
before initiating insulin therapy to guide 
supplementation; if extremely low, insulin 
therapy may need to be delayed (hours) until 
serum potassium concentration increases.
• Refractory hypokalemia may indicate 
hypomagnesemia, requiring magnesium 
replacement at 0.75–1 mEq/kg/24h IV as 
magnesium chloride or magnesium sulfate.
• Supplementation of potassium should start 
at 0.2 mEq/kg/h, which can be adjusted to 
max 0.5 mEq/kg/h. Potassium concentration 
should be measured q6 ­8h until stabilized.
Dextrose Supplementation
• Because insulin is required to correct the 
ketoacidotic state, the supplementation of 
dextrose allows continuous insulin admini­
stration without hypoglycemia.
• Whenever blood glucose <200 mg/dL, 50% 
dextrose should be added to fluids to produce 
2.5% dextrose solution (increase to 5% dextrose 
if glucose <100 mg/dL). Discontinue dextrose 
once glucose is maintained above 250 mg/dL.
• Insulin therapy is continued as long as 
blood glucose >100 mg/dL
Bicarbonate Supplementation
• Controversial; consider if patient’s venous 
blood pH <7.0 or HCO3– <11 mEq/L; of 
little benefit if pH >7.0.
• Dosage—bodyweight (kg) × 0.3 × base 
deficit (base deficit = normal serum bicarb­
onate – patient’s serum bicarbonate); slowly  
administer ¼ to ½ of dose IV and give 
remainder in fluids over 3–6h.• Recheck blood gas or serum total carbon 
dioxide (TCO2) before further supplementation.
Phosphorus Supplementation
• Pretreatment serum phosphorus is usually 
normal; however, treatment of ketoacidosis 
reduces phosphorus, and serum concen­
trations should be checked q12–24h once 
supplementation is initiated.
• Dosage—0.01–0.03 mmol/kg/h for 6–12h 
in IV fluids (may need to increase dose to 
0.06 mmol/kg/h). Remember to account for 
additional potassium in potassium phosphate 
if supplemented.
If the patient anuric or oliguric or if blood 
potassium concentration >5 mEq/L, do not 
supplement potassium until urine flow is 
established or potassium concentration decreases.
• Use bicarbonate with caution in patients 
without normal ventilation (cannot excrete 
carbon dioxide created during treatment).
• Acidosis results in falsely elevated blood 
ionized calcium concentrations; calcium 
should be rechecked as acidosis resolves and 
supplemented as necessary.
None
None
  FOLLOW-UP
• Attitude, hydration, cardiopulmonary 
status, urine output, and bodyweight.
• Blood glucose q1–3h initially; q6h once stable.
• Electrolytes q4–8h initially; q24h once stable.
• Acid­base status q8–12h initially; q24h 
once stable.
Appropriate insulin administration.
• Cerebral edema.
• Pulmonary edema/heart failure.
Guarded
• Hyperadrenocorticism.• Diestrus.
• Bacterial infection.
• Electrolyte depletion.
N/A
N/A
• Risk of fetal death may be relatively high.
• Glucose regulation is often difficult in 
SYNONYMS
N/A
SEE ALSO
• Diabetes Mellitus Without Complication—  
Cats.
Dogs.
• DKA = diabetic ketoacidosis.
• TCO2 = total carbon dioxide.
Behrend E, Holford A, Lathan P , et al. 2018 
AAHA diabetes management guidelines for 
dogs and cats. J Am Anim Hosp Assoc 
2018, 54:1–21.
Difazio J, Fletcher DJ. Retrospective 
comparison of early ­ versus late ­insulin 
therapy regarding effect on time to 
resolution of diabetic ketosis and ketoacido­
sis in dogs and cats: 60 cases (2003–2013). 
J Vet Emerg Crit Care 2016, 26:108–115.
Hume DZ, Drobatz KJ, Hess RS. Outcome 
of dogs with diabetic ketoacidosis: 127 dogs 
(1993–2003). J Vet Intern Med 2006, 
20(3):547–555.
Kerl ME. Diabetic ketoacidosis: pathophysiology 
and clinical and laboratory presentation. Comp 
Cont Educ Pract Vet 2001, 23:220–228.
Kerl ME. Diabetic ketoacidosis: treatment 
recommendations. Comp Cont Educ Pract 
Vet 2001, 23:330–339.
Malerba E, Mazzarino M, Del Baldo F , et al. 
Use of lispro insulin for treatment of 
diabetic ketoacidosis in cats. J Fel Med Surg 
2019, 21:115–123.
Sieber ­Ruckstuhl NS, Klev S, Tschuor F , et al. 
Remission of diabetes mellitus in cats with 
diabetic ketoacidosis. J Vet Intern Med 
2008, 22:1326–1332.
Author  Katherine Gerken
Deborah S. Greco.
available onlineDiabetes Mellitus With Ketoacidosis  (continued)

Canine and Feline, Seventh Edition  397
D
Diabetes Mellitus Without Complication—Cats
  BASICS
• Disorder of carbohydrate, fat, and protein 
metabolism caused by an absolute or relative 
insulin deficiency, resulting in the hallmark 
abnormality of persistent hyperglycemia.
• The most common form in cats resembles 
Type II or non-insulin-dependent diabetes 
mellitus (DM) of humans.
• Insulin resistance impairs the ability of 
tissues (especially muscle, adipose tissue, and 
liver) to use carbohydrates, fats, and proteins.
• Impaired systemic glucose utilization 
coupled with ongoing hepatic gluconeogen-
esis causes persistent hyperglycemia, which 
directly impairs insulin secretion by reducing 
functional beta cell mass (“glucose toxicity”).
• Initial beta cell dysfunction progresses to 
irreversible failure of insulin production as 
reactive oxidative species, inflammatory 
cytokines, and amyloid deposition perpetuate 
beta cell injury and loss.
• Endocrine/metabolic—electrolyte 
depletion, metabolic acidosis.
• Hepatobiliary—chronic pancreatitis, 
hepatic lipidosis.
• Neuromuscular—muscle wasting, 
peripheral neuropathy.
• Renal/urologic—osmotic diuresis with 
compensatory polydipsia (PD); urinary tract 
GENETICS
Genetic susceptibility suspected in certain 
breeds (e.g., European Burmese cats).
Reported at between ~1 : 250 (0.4%) to 
~1 : 100 (1.2%) cats.
N/A
Species
Cat
Breeds with possible increased susceptibility 
include Burmese (Europe, Australia, and 
New Zealand), Maine Coon, Russian Blue, 
Siamese, and Norwegian Forest cats.
Over 80% of cases are 7 years or older at 
diagnosis; range: 1–19 years.
Males are overrepresented, but common in 
both sexes.
SIGNS
• Obesity often present prior to diagnosis.• Polyuria (PU)/PD, polyphagia, weight 
loss, generalized muscle wasting, poor 
coat quality.
• Signs suggesting a complication—anorexia, 
lethargy, depression, vomiting, jaundice.
Physical Exam Findings
Hepatomegaly, dehydration, plantigrade 
stance (diabetic neuropathy).
CAUSES
• Genetic susceptibility.
• Islet amyloid deposition.
• Diseases causing insulin resistance (e.g., 
hyperadrenocorticism and acromegaly).
• Drugs (e.g., glucocorticoids and 
progestogens).
• Obesity.
• Advanced age.
  DIAGNOSIS
• Stress hyperglycemia—no PU/PD or 
weight loss; blood glucose concentration 
normal if sample taken when cat is not 
stressed; normal fructosamine concentration.
• Renal glucosuria—absence of 
hyperglycemia; usually does not cause PU/PD 
or weight loss.
• Mild normocytic, normochromic anemia 
possible.
• Glucose >150 mg/dL.
• High alkaline phosphatase (ALP), alanine 
aminotransferase (ALT), and aspartate 
aminotransferase (AST) activities.
• Hypercholesterolemia, hyperbilirubinemia, 
and hypertriglyceridemia.
• Total CO2 or HCO3 low with ketoacidosis 
or severe dehydration.
• Glucosuria, ketonuria uncommon in 
uncomplicated DM.
• Isosthenuria, proteinuria.
• Fructosamine >350  μmol/L—confirms 
persistence of hyperglycemia.
• Feline pancreas-specific lipase >3.50  μg/L—
identifies presence of pancreatitis.
• Urine culture—positive in 10–15% of 
newly diagnosed DM.
IMAGING
• Thoracic and abdominal radiography— to 
evaluate for concurrent or underlying disease 
(e.g., neoplasia, cystic or renal calculi, 
emphysematous cystitis, or cholecystitis).
• Abdominal ultrasonography—in selected 
patients, particularly those with jaundice, to 
evaluate for hepatic lipidosis, cholangio -
hepatitis, and pancreatitis.DIAGNOSTIC PROCEDURES
Liver fine-needle aspiration—if concern for 
• Usually no gross necropsy changes; 
pancreatic weight may be increased.
• Histopathology—normal, more likely to 
reveal islet amyloidosis, vacuolar or hydropic 
degeneration of the islets of Langerhans; 
lymphoplasmacytic pancreatic infiltration 
rare in cats.
  TREATMENT
• Compensated cats can be managed as 
outpatients if they are alert, hydrated, and 
eating and drinking without vomiting.
• For decompensated patients, see Diabetes 
Mellitus With Ketoacidosis.
Fluid therapy—in decompensated patients.
ACTIVITY
Strenuous activity may lower insulin require  - 
ments; consistent daily activity level is helpful.
DIET
Ultra-low-carbohydrate (<12% metabolizable 
energy) and high protein (>40% metabolizable 
energy) canned diets may improve glycemic 
control, and increase the likelihood of 
diabetic remission in newly diagnosed 
diabetic cats.
• Discuss maintaining a consistent daily 
feeding and medication schedule, home glucose 
monitoring, signs of hypoglycemia and what to 
do, and when to seek veterinary assistance.
• Clients are encouraged to chart pertinent 
daily information about the pet, such as any 
home-obtained glucose readings or patterns 
of exhibited clinical signs (e.g., PU/PD or 
appetite).
Intact females should have ovariohysterectomy 
when stable; progesterone secreted during 
diestrus makes management of DM difficult.
• Insulin is treatment of choice and should be 
initiated at 1–2 units per cat SC q12h; based 
on routine monitoring, some cats may 
eventually be reduced to once-daily dosing.
• T wo U-40 insulin formulations are FDA-
approved for use in cats—protamine zinc (PZI) 
and porcine zinc lente insulin suspension.

398  Blackwell’s Five-Minute Veterinary Consult  
D• Most consensus recommendations support 
the use of PZI or glargine (U-100) as 
first-choice insulin therapy for cats.
Glucocorticoids, megestrol acetate, and 
progesterone cause insulin resistance. If 
steroid therapy is necessary, use oral 
methylprednisolone. Avoid injectable steroids.
• Drugs that may increase insulin sensitivity—  
sulfonamides, tetracycline, beta blockers, 
monoamine oxidase inhibitors, salicylates.
• Drugs that increase insulin resistance—
glucocorticoids, estrogen supplements, 
furosemide, thiazide diuretics, and calcium 
channel blockers.
• Always consult a new medication’s product 
insert.
• Oral sulfonylureas (e.g., glipizide)—only 
considered when insulin therapy is not 
possible (e.g., owner considering euthanasia 
instead of injections). Initial does of 2.5 mg 
PO q12h can be used and monitored 
similar to insulin. If DM is not controlled 
after 2 weeks, dose of 5 mg PO q12h may 
be tried; however, response is seen in <40% 
of cats and often not sustained long term. 
Potential side effects are hypoglycemia, 
hepatic enzyme alterations, icterus, and 
vomiting.
• Acarbose—an alpha-glucosidase 
inhibitor used to limit intestinal glucose 
absorption. Often used in combination 
with diet and insulin at a starting dose of 
12.5 mg PO q12h; diarrhea is most 
common side effect.
• Drugs warranting further study for utility 
in managing feline DM include once-weekly 
injected glucagon-like peptide 1 analogues 
and oral renal tubular transporter inhibitors.
  FOLLOW-UP
• Owner-assessed clinical signs (PU/PD, 
appetite, attitude) and bodyweight—if signs are normal and weight stable to increasing, 
disease is likely to be regulated.
• Glucose curves—ideally generated by the 
owner at home. Perform 5–14 days after 
starting insulin or after any dose adjustments 
until controlled, then again at 1 month, and 
every 3–6 months thereafter.
• Fructosamine—maintain <400 μmol/L. 
Recheck monthly during initial regulation, 
then every 3–6 months as part of routine 
monitoring visits.
• Urinary monitoring—useful for identifying 
ketones in chronically unregulated patients or 
persistently negative glucose in cats likely 
entering remission.
• Flash glucose monitoring system (FreeStyle 
Libre®)—24-hour glucose monitoring system 
that measures blood glucose BG every 5 
minutes for up to 14 days; use reported in 
dogs, but not cats. Anecdotal evidence 
suggests the device is not 100% accurate, but 
helpful in assessing BG trends in cats in 
which a BG curve is not possible.
Prevent or correct obesity; avoid unnecessary 
use of glucocorticoids or megestrol acetate.
• Seizure, blindness, or coma with insulin 
overdose.
• Diabetic ketoacidosis or hyperglycemic 
hyperosmolar syndrome.
• Prognosis with treatment and monitoring is 
good; most animals have a normal lifespan.
• Some cats may recover insulin-secreting 
ability (“diabetic remission”), typically if 
glycemic control is achieved within 6 months 
of diagnosis; however, relapse is common (~30%).
• Reported remission rates vary greatly 
(0–100%); however, studies surveying general 
practitioners have suggested ~25–30% is 
reasonable expectation.
Urinary tract infection, chronic pancreatitis.AGE-RELATED FACTORS
Congenital and juvenile forms of DM are rare 
(<3% of cases are under 2 years of age) and 
may be more difficult to manage.
None
• Insulin requirements should be monitored 
closely during pregnancy as they are expected 
to fluctuate.
• Severe maternal hypoglycemia can negatively 
impact fetal viability and neonatal neurologic 
function, therefore should be avoided during 
gestation.
SYNONYMS
N/A
SEE ALSO
• Diabetes Mellitus With Hyperosmolar 
Hyperglycemic State.
• DM = diabetes mellitus.
• PU/PD = polyuria and polydipsia.
• PZI = protamine zinc insulin.
https://www.aaha.org/guidelines/diabetes_
guidelines/default.aspx
Sparkes A, Cannon M, Church D, et al. 
ISFM consensus guidelines on the practical 
management of diabetes mellitus in cats. J 
Feline Med Surg 2015, 17:235–250.
Author  Andrew C. Bugbee
of Deborah S. Greco.
available onlineDiabetes Mellitus Without Complication—Cats  (continued)

Canine and Feline, Seventh Edition  399
D
Diabetes Mellitus Without Complication—Dogs
  BASICS
• Fasting hyperglycemia of sufficient 
magnitude to result in characteristic clinical 
signs including weight loss with normal or 
increased appetite, polydipsia (PD), and 
polyuria (PU) caused by glucosuria. 
metabolism caused by absolute or relative 
insulin deficiency. • Generally canine 
diabetes mellitus (DM) is characterized by 
loss of insulin-secreting ability through 
presumed immune-mediated destruction of 
pancreatic beta cells. • Far less frequently, 
canine DM may develop as result of 
combination of relative insulin-deficient 
state with concurrent peripheral insulin 
• Absolute or relative insulin deficiency 
results in accelerated tissue catabolism, 
impaired ability to maintain carbohydrate, 
lipid, and protein homeostasis, as well as 
insulin resistance. • Reduced insulin-
secreting ability, peripheral insulin resistance, 
and continued hepatic gluconeogenesis result 
in persistent hyperglycemia of sufficient 
severity to overload renal tubular glucose 
resorption; leading to glucosuria, osmotic 
diuresis, PU accompanied by compensatory 
PD. • Loss of insulin-dependent glucose-
mediated hypothalamic satiation signaling 
results in polyphagia. • Decreased insulin-
dependent utilization of glucose results in 
catabolic protein breakdown with weight loss 
and increased lipid mobilization (hyperlipi -
demia, hepatic lipidosis, production of 
ketoacids). • Accumulation of large amounts 
of ketone bodies leads to metabolic acidosis 
(see Diabetes Mellitus With Ketoacidosis).
• Endocrine/metabolic—electrolyte depletion 
and metabolic acidosis. • Hepatobiliary—
hepatic lipidosis. • Ophthalmic—cataracts. 
• Renal/urologic—glucosuria resulting in 
osmotic diuresis and increased likelihood of 
bacterial urinary tract infections, particularly 
of upper urinary tract.
GENETICS
Certain breeds dramatically over- and 
underrepresented, suggesting inherited 
susceptibility to immune-mediated “isletitis.”
• Prevalence varies between 1 : 400 and 
1 : 500. • Onset has seasonal incidence; more 
animals diagnosed in autumn and winter.
Species
DogBreed Predilections
• Samoyed, Tibetan terrier, Cairn terrier, 
golden retriever (United States only) 
overrepresented. • Keeshond, poodle, 
dachshund, miniature schnauzer, beagle may 
have increased predisposition. • Boxer, 
German shepherd, golden retriever (UK only) 
underrepresented.
Mean ~8 years; range: 4–14 years (excluding 
rare juvenile form).
Female
SIGNS
• PU/PD, polyphagia with weight loss. 
• Hepatomegaly. • Cataracts common 
finding—approximately 80% of dogs with 
DM for >12 months will have cataracts 
regardless of level of control. • Lethargy, 
depression, inappetence, anorexia, and 
vomiting may occur in animals with keto  - 
acidosis.
CAUSES
• Immune-mediated isletitis. • Disorders that 
predispose to secondary immune-mediated 
isletitis—pancreatitis, viral illness.
• Diestrus. • Genetic susceptibility. • Use of 
glucocorticoids or progestins.
  DIAGNOSIS
Renal glucosuria—not associated with hyper  - 
glycemia, usually no weight loss or 
polyphagia.
• Hemogram usually normal. • Glucose 
>200 mg/dL, possible ketonemia. • High 
serum alkaline phosphatase (ALP) and 
alanine aminotransferase (ALT) enzyme 
activities, generally with greater proportionate 
increase in ALP . • Hypercholesterolemia, 
lipemia. • Electrolyte alterations vary; 
hypokalemia and hypophosphatemia may be 
present. • Total CO2 or HCO3 will be low 
with ketoacidosis or severe dehydration. 
• Glucosuria, ketonuria in some dogs. 
• Urinary specific gravity variable depending 
on degree of glucosuria.
• Anion gap—high in patients with 
ketoacidosis. • Glycated proteins—
fructosamine or glycosylated hemoglobin: 
extent of glycosylation directly related to 
blood glucose concentration over lifespan of 
protein in circulation (10–20 days for 
fructosamine, 4–8 weeks for hemoglobin). 
◦ Glycated protein concentration modified 
by changes in albumin or hemoglobin 
concentrations; accelerated albumin turnover (e.g., glomerulonephropathy, liver 
dysfunction, gastrointestinal disease) will 
lower fructosamine level for given average 
blood glucose. ◦ Best used for ongoing 
management of relatively stable diabetic 
patients; fructosamine concentration in upper 
third of reference range reflects excellent 
diabetic control; concentration in lower third 
is more suggestive of overzealous diabetic 
control and possible increased risk of 
hypoglycemia. • Plasma insulin concen -
trations not particularly helpful—while low 
insulin concentration suggests insulin 
deficiency, may be reflection of reversible islet 
exhaustion (persistent hyperglycemia can 
impair insulin secretory activity, even if 
functional beta cells present).
IMAGING
• Radiography—useful to look for 
comorbidities (e.g., cystic or renal calculi, 
emphysematous cystitis, cholecystitis, 
pancreatitis). • Ultrasonography—indicated 
in selected patients, particularly those with 
jaundice, to evaluate for presence of 
obstructive hepatopathy or pancreatitis.
Liver biopsy (percutaneous)—indicated in 
some jaundiced patients to evaluate other 
causes for hepatopathy.
• Necropsy findings—hepatomegaly with 
significant hepatic lipid accumulation. 
• Histopathologic findings generally reveal 
dramatic reduction in size and number of 
pancreatic islets with relatively normal 
exocrine tissue architecture.
  TREATMENT
• Compensated dogs generally alert, well 
hydrated, eating and drinking without 
vomiting, and can be managed as outpatients. 
• For management of decompensated 
patients, see Diabetes Mellitus With 
Ketoacidosis.
DIET
• Diet should be calorically and constitutively 
consistent. • Ideally glucose-lowering effects 
of insulin should match glucose-raising effects 
of the meal. ◦ Most insulins act maximally 
2–4h after SC administration, and most food 
absorbed within 1h of consumption, so 
glycemic control almost always improved if 
dog fed 60–90 min after q12h insulin dosing. 
◦ Animals that “graze” throughout day can be 
fed dry food ad libitum and given 2 small 
meals of canned food as above. ◦ If insulin 
can only be administered once daily, feed 
total daily caloric intake in 2 or 3 meals 
within first 6–8h after insulin dosing. • Feed 
caloric quantity appropriate for animal’s ideal

400  Blackwell’s Five-Minute Veterinary Consult  
Dbodyweight (~60 kcal/kg); food should be 
something dog will eat reliably and within 
short period. • Obese diabetic dogs—feed 
restricted caloric intake to ensure ideal 
bodyweight achieved within 2–4 months 
using high-fiber, low-calorie food; while 
high-fiber diet may improve patient satiety 
and possibly owner satisfaction, has no role in 
improving diabetic control. • While snacks 
should generally be avoided, small treats given 
at time of injection to positively reinforce 
owner–patient interaction should be 
encouraged.
• Most important that insulin and feeding 
regime are discussed and agreed with owner 
and they feel comfortable with plan; effective 
management requires significant owner–
patient interaction; flexibility in establishing 
best management regime is thus paramount 
and rigid “one size fits all protocols” should 
be avoided. • Discuss daily feeding and 
medication schedule, home monitoring, signs 
of hypoglycemia and what to do, and when to 
call or visit veterinarian. • Clients encouraged 
to keep chart of pertinent information about 
pet, such as daily water consumption, weekly 
bodyweight, current insulin dose, and 
amount of food consumed; use of standardized 
clinical scoring tool should be encouraged to 
maintain consistency across veterinary and 
tech teams involved in managing both dog 
and owner.
Intact females should have ovariohysterec-
tomy when stable; progesterone secreted 
during diestrus makes management of DM 
more unpredictable.
• Insulin—almost always required • Vetsulin® 
(porcine-origin lente) 0.75 units/kg SC q12h 
initial dose; note: U-40 insulin—must use 
with U-40 insulin syringe; availability may be 
limited. • Humulin N—intermediate-acting, 
human insulin; 0.75 units/kg SC q12h initial 
dose. • Novolin N—intermediate-acting, 
dose. • PZI Vet® (intermediate- to longer-
acting protamine zinc human insulin) rarely 
used in dogs; note: U-40 insulin—must use 
with U-40 syringe. • Detemir insulin—
longer-acting, synthetic insulin; part of reason 
for its delayed release is because bound to 
albumin; unlike insulins mentioned above, 
starting dose should be considerably lower: 
0.1 unit/kg SC q12h initial dose. • Glargine 
insulin—longer-acting, synthetic insulin; 
0.75 units/kg SC q12h initial dose. • Species of 
origin of insulin may affect pharmacokinetics; canine and porcine insulin have identical 
amino acid sequence, hence Vetsulin does not 
produce significant insulin antibody response, 
whereas most other commercially available 
insulins do; however, no evidence the 
development of insulin antibodies has any 
clinical significance.
• Glucocorticoids, megestrol acetate, and 
progesterone cause insulin resistance. 
• Hyperosmotic agents (e.g., mannitol and 
radiographic contrast agents) should be 
avoided if patient is already hyperosmolar 
from hyperglycemia.
Oral hypoglycemic agents are generally not 
  FOLLOW-UP
• Diabetic dogs require regular contact 
between owner and veterinary team; visits 
should occur every 3–4 months if animal is 
stable and clinical signs are controlled, or 
more frequently if control is poor or variable. 
Criteria to assess control include: ◦ Clinical 
signs—degree of PU/PD, appetite, and 
bodyweight; if within acceptable limits, 
disease likely well regulated; consider using 
standardized clinical scoring system to 
consistently evaluate clinical phenotype. 
◦ Glycated proteins—fructosamine or 
glycosylated hemoglobin; see above. 
◦ Glucose curve—provides information on 
insulin effectiveness, duration of action, 
nadir (lowest blood glucose level achieved 
during dosing interval), and potential for 
rebound hyperglycemia; results subject to 
influence of stress (hospitalization, multiple 
blood draws) and “normal” conditions 
should be mimicked as much as possible; 
used most effectively when establishing 
initial control, changing insulin type, dose, 
or frequency, or problem solving for difficult 
diabetic; duration of curve ideally matches 
dosing interval (12 or 24 hours)—identifi -
cation of nadir (to avoid iatrogenic 
hypoglycemia) and glucose level at time of 
dosing are most important aspects of curve; 
goal is to establish effective insulin dose 
(decline in blood glucose to 100–200 mg/
dL) for appropriate duration (majority of 
12- or 24-hour dosing interval) with nadir 
>80 mg/dL and <150 mg/dL; in dogs 
average glucose levels for 12-hour period 
overnight are lower than during daylight 
period. • Home glucose monitoring using 
serial blood glucose estimations or real-time 
measures using SC glucose monitoring 
devices—requires owner commitment, 
compliance, and competence; most useful as early indicator of need for reduction in dose 
in patients with well-controlled clinical signs; 
should never be used by owner to make 
independent adjustment of insulin dose; 
owner-measured urine glucose levels not 
particularly useful.
• Neuter females; avoid unnecessary use of 
megestrol acetate. • No evidence exists to 
suggest obesity increases risk of DM in 
neutered dogs.
• Cataracts can occur even with good glycemic 
control. • Weakness, especially with exercise; 
seizures or coma may occur with insulin 
overdose.
• Dogs generally have permanent disease 
unless affected during estrus cycle, where 
neutering may resolve diabetes for a period. 
• Prognosis with twice-daily insulin treatment 
and feeding aligned with insulin’s maximum 
effects is good.
• Urinary tract infection. • Cataracts.
Juvenile DM is rare and may be more 
difficult to manage.
• DM can develop during pregnancy, in 
which case pregnancy is difficult to maintain. 
• Exogenous insulin administration may 
cause fetal oversize and dystocia. • Insulin 
resistance develops, making hyperglycemia 
difficult to control. • Pregnant bitch is prone 
to ketoacidosis; emergency ovariohysterectomy 
may be necessary. • Do not breed dogs 
with DM.
Author  David B. Church
available onlineDiabetes Mellitus Without Complication—Dogs  (continued)

Canine and Feline, Seventh Edition  401
DDiaphragmatic Hernia
  BASICS
OVERVIEW
• Protrusion of an abdominal organ through 
an abnormal opening in the diaphragm, either 
as an acquired injury or as a congenital defect. 
• Congenital—pleuroperitoneal (PIPDH) or 
peritoneopericardial diaphragmatic hernia 
(PPDH). •  T raumatic—most often the result 
of a motor vehicle accident. •  Impaired lung 
expansion. •  Myocardial trauma. •  Evidence 
of shock. •  Systems affected —respiratory, 
cardiovascular, gastrointestinal.
• Dogs and cats. •  Acquired—no breed predil  - 
ection. •  Congenital (PPDH)—Weimaraner, 
Maine coon cat, and Persian cats. 
• Congenital PIPDH—golden retriever, 
cavalier King Charles spaniel. •  Young 
animals at higher risk for both congenital and 
traumatic causes (median age 1.2 and 3.1 
years, respectively). •  No sex predilection.
SIGNS
Traumatic
• Can be acute, subacute, or chronic. •  Possible 
known history of blunt trauma. •  Difficulty 
breathing. •  Evidence of shock (tachycardia, 
pale mucous membranes, weak pulses). 
• Gastrointestinal sounds ausculted in thorax. 
• Empty abdomen on abdominal palpation. 
• Signs may be progressive.
• May not have clinical signs or may develop 
clinical signs later in life. •  Difficulty 
breathing. •  Gastrointestinal signs. •  Signs 
may be progressive. •  Evidence of shock 
(tachycardia, pale mucous membranes, weak 
pulses). •  Evidence of cardiac tamponade. 
• Arrhythmias. •  Muffled heart sounds.
Traumatic
• Motor vehicle accident. •  Other blunt trauma. 
• Penetrating trauma (e.g., bite wounds).
  DIAGNOSIS
• Pneumothorax. • Pulmonary contusion. 
• Hemothorax.
Nonspecific changes due to trauma may be noted.
Serum lactate—may be significantly elevated 
following trauma.
IMAGING
Point-of-Care Ultrasound (POCUS)
• Thoracic-focused assessment with 
sonography for trauma (TFAST®). 
• Abdominal focused assessment with 
sonography for trauma (AFAST®).Standard Imaging
• Three-view thoracic and abdominal 
radiography. •  Horizontal beam radiography. 
• Ultrasonography.
Additional Imaging
• Contrast radiography—upper gastrointestinal 
positive contrast series; peritoneography. •  CT.
Imaging Findings
• Identification of gastrointestinal viscera 
within pleural space and/or absence from 
abdominal cavity makes diagnosis of 
diaphragmatic herniation often uncomplicated. 
• Other radiographic signs include loss of 
diaphragmatic outline and cardiac silhouette, 
displacement of lung fields, presence of 
gas-filled viscera, and pleural effusion.•  For 
congenital PPDH cardiac silhouette is 
markedly enlarged and may have evidence of 
gas-filled structures within it. •  Contrast or 
advanced imaging is often unnecessary.
• Thoracocentesis for pleural effusion. 
• Pericardiocentesis for pericardial effusion.
  TREATMENT
Emergency Inpatient Intensive Care 
Management
• Address shock. •  Improve ventilation and 
cardiac output. •  Manage concurrent injury. 
• Gastric decompression if indicated.
Surgical Management
• Exploratory laparotomy. •  Reduction and 
assessment of herniated abdominal viscera. 
• Surgical repair of diaphragmatic rent. 
• Additional surgical procedures (e.g., splenec -
tomy, intestinal resection and anastomosis, liver 
lobectomy). •  Pleural space evacuation 
(thoracostomy tube placement, thoracocentesis).
• IV fluid therapy. •  Oxygen supplement -
ation. •  Pain management.
• Anesthesia and surgery should be delayed 
until animal is hemodynamically stable. 
• Emergency surgery indicated with evidence of 
gastrothorax, gastrointestinal entrapment, or 
persistent respiratory distress. •  Long lasting 
absorbable monofilament suture (e.g., Maxon® 
or PDS®) should be used to close the diaphragm 
in a full-thickness simple continuous pattern. 
• Care should be taken around caval foramen, 
esophageal hiatus, and aortic hiatus.
• Appropriate postoperative pain medic  ations; 
consider local analgesia. •  Antiarrhythmic 
agents as indicated.CONTRAINDICATIONS
Avoid nonsteroidal anti-inflammatories for at 
least 24–48 hours following trauma.
  FOLLOW-UP
• Frequent or continuous ECG monitoring. 
• Observation of ventilation. •  Pulse 
oximetry. •  Serial arterial blood gas 
• Respiratory distress—due to concurrent 
injury or pneumothorax. •  Reexpansion 
pulmonary edema (RPE) is uncommon but 
often fatal complication; to minimize risk of 
RPE, avoid aggressive positive-pressure 
ventilation following reduction of herniated 
organs, and avoid aggressive evacuation of 
pleural space in postoperative period. 
• Recurrence uncommon, but most often 
associated with inadequate surgical repair.
If animal survives for first 12–24 hours after 
surgery, prognosis is excellent. Reported 
survival rates range from 80 to 90%. Death 
most often due to concurrent injury.
• Congenital PPDH may be associated with 
other congenital midline defects. • Animals 
suffering trauma may have significant 
concurrent injuries.
• AFAST® = abdominal focused assessment 
with sonography for trauma.
• PIPDH = pleuroperitoneal diaphragmatic 
hernia.
• POCUS = point-of-care ultrasound.
• PPDH = peritoneopericardial 
diaphragmatic hernia.
• RPE = reexpansion pulmonary edema.
• TFAST® = thoracic-focused assessment with 
Burns CG, Bergh MS, McLoughlin MA. 
Surgical and nonsurgical treatment of 
in dogs and cats: 58 cases (1999–2008). J 
Am Vet Med Assoc 2013, 242:643–650.
Legallet C, Thieman Mankin K, Selmic LE. 
Prognostic indicators for perioperative 
survival after diaphragmatic herniorrhaphy 
in cats and dogs: 96 cases (2001–2013). 
BMC Vet Res 2017, 13:16.
Author  Catriona M. MacPhail

402  Blackwell’s Five-Minute Veterinary Consult  
DDiarrhea, Antibiotic Responsive
  BASICS
OVERVIEW
• Defined as chronic diarrhea with no ident  - 
ifiable underlying etiology that responds to 
antibiotic therapy. •  Antibiotic-responsive 
diarrhea (ARD) was previously termed 
idiopathic (primary) small intestinal bacterial 
overgrowth (SIBO); this term is no longer used 
as it was based on quantitative culture of bacteria 
in the upper gastrointestinal tract that could not 
be confirmed by newer PCR-based methods; 
secondary SIBO is a result of concurrent 
gastrointestinal diseases (e.g., exocrine pancreatic 
insufficiency [EPI]). •  Current theories center 
on the possibility of immune dysregulation, 
possibly associated with abnormal CD4+ T-cells, 
immunoglobulin (Ig) A plasma cells, cytokine 
expression, and, in German shepherd dogs, 
mutations in pattern recognition receptors.
Species
Dog
Increased incidence in German shepherd, 
boxer, and Chinese Shar-Pei.
More common in young dogs, with median 
age of 2 years.
N/A
SIGNS
• Small bowel signs—inappetence or anorexia, 
vomiting, weight loss, large-volume diarrhea. 
• Large bowel signs—tenesmus, hematochezia, 
increased frequency of defecation.
Weight loss, poor body condition, borboryg-
mus, and flatulence may be detected; hemato  - 
chezia may be present if there is large bowel 
• Genetic mutations in pattern recognition genes 
(TLR4  and TLR5 ) have been associated with the 
disease. •  Certain enteropathogenic bacteria 
(Clostridium perfringens , Escherichia coli , and 
Lawsonia intracellularis ) have been suspected but 
not proven to be etiologic agents.
  DIAGNOSIS
• Secondary SIBO. •  EPI. •  Parasitic 
infection. •  Inflammatory bowel disease. 
• Food-responsive diarrhea. •  Neoplasia.CBC/BIOCHEMISTRY/URINALYSIS
• Typically normal. •  Hypoalbuminemia is 
uncommon finding.
• Fecal examination for parasites should be 
performed. •  Serum cobalamin levels may be 
low and folate levels may be increased or 
decreased. •  Serum trypsin-like immunoreac-
tivity (measured to rule out EPI) is normal.
IMAGING
Routine abdominal imaging (radiographs and 
ultrasound) should be performed to rule out 
other causes for diarrhea. These tests are 
unremarkable in cases of ARD.
Diagnosis depends upon ruling out all other 
causes for chronic diarrhea (especially 
food-responsive diarrhea) and a clinical 
response to an appropriate course of 
antibiotic therapy.
  TREATMENT
• Hospitalization generally not indicated; 
treated on outpatient basis. •  Role of diet in 
ARD is unknown; current recommendations 
are to feed low-fat, highly digestible food or 
elimination or hydrolyzed diet.
• Several options for antibiotics available—
tylosin (5–10 mg/kg PO q24h); metronida-
zole (10–15 mg/kg PO q12h); oxytetracycline 
(10–20 mg/kg PO q8h). •  In some cases, 
combination therapy may be necessary. 
• Antibiotic therapy administered for 4–6 
weeks and then discontinued. •  If serum 
cobalamin levels decreased, cobalamin 
supplementation should be pursued; dogs: 
50 μg/kg up to max dose of 1,500  μg 
parenteral cobalamin; doses given as SC 
injections once weekly for 6 weeks, then once 
every other week for 6 weeks; serum 
cobalamin levels should be reassessed at end 
of therapy; oral cobalamin supplementation is 
effective at dosage of 0.25–1.0 mg PO daily.
• Oxytetracycline may cause staining of tooth 
enamel; doses should be decreased in animals 
with hepatic or renal insufficiency; oxytetra-
cycline has been associated with high 
incidence of bacterial transfer of resistance 
genes. •  Metronidazole undergoes extensive 
hepatic metabolism; dosages should be 
reduced in animals with hepatic insufficiency. • Long-term administration of both tylosin 
and metronidazole has been found to induce 
long-term dysbiosis in ARD dogs, which is 
very difficult to correct; this dysbiosis is 
associated with changes in bile acid metabo-
lism and serum metabolome, and persists for 
over 6 months after discontinuing treatment.
  FOLLOW-UP
• Clinical resolution of diarrhea is most 
important criterion. •  Weight gain may also be 
seen; hypoalbuminemia (if present) should 
resolve. •  Relapses usually occur when anti  - 
biotics are discontinued; some dogs can be 
maintained on very low doses of antibiotics long 
term, however the development of antimicrobial 
resistance in these dogs is a concern. •  Recent 
studies suggest ARD dogs have poor long-term 
prognosis, possibly due to induction of dysbiosis; 
many dogs eventually will become steroid 
resistant or will be euthanized because of 
treatment resistance.
SEE ALSO
Small Intestinal Dysbiosis.
 ABBREVIATIONS
• ARD = antibiotic-responsive diarrhea.
• SIBO = small intestinal bacterial overgrowth.
Suggested Reading
Allenspach K, Culverwell C, Chan D. 
Long-term outcome in dogs with chronic 
enteropathies: 203 cases. Vet Rec 2016, 
178(15):368. doi: 10.1136/vr.103557
German AJ, Day MJ, Ruaux CG, et al. 
Comparison of direct and indirect tests for 
small intestinal bacterial overgrowth and 
antibiotic-responsive diarrhea in dogs. J Vet 
Intern Med 2003, 17:33–43.
Toresson L, Steiner JM, Spodsberg E, et al. 
Effects of oral versus parenteral cobalamin 
supplementation on methylmalonic acid 
and homocysteine concentrations in dogs 
with chronic enteropathies and low 
cobalamin concentrations. Vet J 2019, 
243:8–14. doi: 10.1016/j.tvjl.2018.11.004
Westermarck E, Skrzypczak T, Harmoinen J, 
et al. Tylosin-responsive chronic diarrhea 
in dogs. J Vet Intern Med 2005, 
19:177–186.
Author  Karin Allenspach

Canine and Feline, Seventh Edition  403
D
Diarrhea, Chronic—Cats
  BASICS
• A change in the frequency, consistency, and 
volume of feces for more than 3 weeks or with a 
pattern of episodic recurrence. • Can be either 
small bowel, large bowel, or mixed in origin.
• High solute and fluid secretion—secretory 
diarrhea. • Low solute and fluid absorption—
osmotic diarrhea. • High intestinal permeability. 
• Abnormal gastrointestinal (GI) motility. 
• Many cases involve various combinations of 
these four basic pathophysiologic mechanisms.
• Endocrine/metabolic—fluid, electrolyte, 
and acid-base. • Exocrine. • GI. • Lymphatic.
GENETICS
N/A
Unknown
Worldwide
Species
Cat
None
Any age.
None
SIGNS
• Underlying disease process determines extent 
of clinical signs. • 2–3% increase of water 
content of stool results in gross description of 
diarrhea. • Classification of small, large, and 
mixed bowel types of diarrhea may have overlap 
of descriptive findings.
• Small bowel diarrhea can include—normal to 
increased volume; normal to moderately 
increased (2–4 times/day) defecation frequency; 
weight loss; polyphagia; melena; flatulence and 
borborygmus; vomiting: variable. • Large 
bowel diarrhea can include—smaller volume; 
frequency of defecation is increased ( >4 times/
day); often hematochezia and mucus; tenesmus, 
urgency, dyschezia; flatulence and borborygmus: 
variable; vomiting: variable.
Small Bowel
• Poor body condition associated with malab  - 
sorption, maldigestion, and protein-losing 
enteropathy (PLE). • Variable dehydration. 
• Abdominal palpation may reveal segmental or 
diffusely thickened small bowel loops associated 
with infiltrative disease, abdominal effusion, 
foreign body, neoplastic mass, intussusception, or enlarged mesenteric lymph nodes. • Rectal 
palpation typically unremarkable.
Large Bowel
• Body condition typically unremarkable. 
• Dehydration—uncommon. • Abdominal 
palpation may reveal thickened large bowel, 
foreign body, neoplastic mass, intussusception, or 
enlarged mesocolic lymph nodes. • Rectal 
palpation may reveal irregularity of rectal mucosa, 
intraluminal or extraluminal rectal masses, rectal 
stricture, or sublumbar lymphadenopathy.
CAUSES
Small and Large Intestinal Diseases
Primary Disease
• Inflammatory bowel disease (IBD)—e.g., 
lymphoplasmacytic enteritis, eosinophilic 
enteritis, granulomatous enteritis. • Neoplasia—
e.g., lymphoma, including large cell (B-cell 
lymphoma) and small cell alimentary lymphoma 
(T-cell), adenocarcinoma, mast cell neoplasia. 
• Bacterial—e.g., Salmonella  spp., enterotoxic 
Escherichia coli , other enterobacteriaceae species, 
Clostridia  spp.: usually acute diarrhea. • Viral—
e.g., enteric coronavirus (usually acute diarrhea 
unless combined with other viral infections or 
co-factors), feline infectious peritonitis, feline 
leukemia virus (FeLV) associated, feline 
immunodeficiency virus (FIV) associated. 
• Mycotic—e.g., histoplasmosis. • Algal—e.g., 
protothecosis, pythiosis. • Parasites—e.g., 
Giardia , Toxocara  spp., Ancylostoma , Toxascaris 
leonina , Cryptosporidium  spp., Cystoisospora  spp., 
Tritrichomonas foetus . • Partial obstruction—e.g., 
foreign body, intussusception, neoplasia. 
• Secondary lymphangiectasia—very rare in cats. 
• Intestinal microbial dysbiosis—cause vs. effect. 
• Short bowel syndrome. • GI ulceration—rare 
in cats.
Maldigestion
• Hepatobiliary disease—lack of bile salts 
needed for intraluminal digestion. • Exocrine 
pancreatic insufficiency (EPI).
Dietary
• Dietary intolerance (food-responsive 
diarrhea). • Food allergy.
Metabolic Disorders
• Hyperthyroidism. • Cobalamin deficiency—
typically secondary to underlying IBD or 
lymphoma. • Renal disease. • Hepatobiliary 
disease. • Adverse drug reactions.
Congenital Anomalies
• Short colon. • Portosystemic shunt. 
• Persistent pancreaticomesojejunal ligament.
Dietary changes, feeding poorly digestible or 
high-fat diets.
  DIAGNOSIS
First localize the origin of the diarrhea to the 
small or large bowel (or both) on the basis of 
historical signs.CBC/BIOCHEMISTRY/URINALYSIS
• Eosinophilia in some cats with parasitism, 
eosinophilic enterocolitis, hypereosinophilic 
syndrome, or neoplasia. • Macrocytosis in 
some cats with hyperthyroidism or FeLV 
infection. • Anemia that is variably 
regenerative and may show microcytosis 
suggests chronic GI bleeding and iron 
deficiency. • Leukopenia in some cats with 
FeLV or FIV infection. 
• Panhypoproteinemia caused by PLE is 
uncommon in cats with intestinal disease, but 
can occur; hypoalbuminemia can be seen. 
• Biochemical profiles and urinalysis 
abnormalities may suggest renal disease, 
hypoproteinemia, hepatobiliary disease, or 
endocrinopathy.
Fecal and/or Rectal Scraping Exam
• Direct wet prep, routine centrifugation fecal 
flotation, fecal ELISA testing may indicate GI 
parasites. • Cytologic examination of rectal 
scrapings may reveal specific organisms, such as 
Histoplasma , Prototheca , or Tritrichomas . • PCR 
fecal testing should be interpreted with caution, 
because positive results for toxin genes or 
infectious agents may or may not correlate with 
clinical disease; interpret PCR results in light of 
patient signalment, history, clinical presentation, 
vaccination history, and other laboratory data. 
• PCR for Tritrichomonas —most sensitive test; 
be certain to send fresh fecal sample, colonic 
lavage fluid, or loop scraping for testing. 
• Culture feces if Salmonella  is suspected—
special media required.
Thyroid Function Tests
• High total T4 or free T4 concentration 
indicates hyperthyroidism. • If hyper -
thyroidism is suspected but T4 is normal, 
perform a T3 suppression test, repeat the T4 a 
few months later, or perform a technetium 
scan of the thyroid glands.
Serologic Testing
Test for FeLV and FIV—especially if 
hematologic abnormalities are present.
Test for Exocrine Pancreatic Function
Feline-specific trypsin-like immunoreactiv-
ity—test of choice for diagnosis of EPI.
IMAGING
• Survey abdominal radiography may indicate 
abnormal intestinal pattern, organomegaly, 
mass, foreign body, pancreatic disease, 
hepatobiliary disease, urinary disease, or 
abdominal effusion; low yield in most cats 
with chronic diarrhea. • Contrast radio -
graphy (upper GI series or barium enema) 
may indicate bowel wall thickening, intestinal 
ulcers, mucosal irregularities, mass, radiolucent 
foreign body, or stricture; procedure performed 
infrequently in cats in light of advantages of 
abdominal ultrasonography. • Abdominal 
ultrasonography may demonstrate bowel wall 
thickening, abnormal bowel wall layering, GI 
or extra-GI masses, intussusception, foreign 
body, ileus, abdominal effusion, hepatobiliary

404  Blackwell’s Five-Minute Veterinary Consult  
Ddisease, pancreatitis, renal disease, or 
mesenteric or mesocolic lymphadenopathy.
If maldigestive (EPI), metabolic, parasitic, 
dietary, and infectious causes have been 
excluded, consider empiric dietary therapy, 
utilizing an elimination diet for 2 weeks 
before performing endoscopy and biopsy or a 
laparotomy for definitive diagnosis.
Endoscopy/Laparoscopy
• Upper GI flexible endoscopy allows exam  - 
ination and biopsy of gastric and duodenal 
mucosa; always obtain multiple (8–10) mucosal 
specimens from each segment/area. • Flexible 
colonoscopy allows examination of entire rectum, 
colon, cecum, and ileum; always obtain multiple 
mucosal specimens (8–10) from each segment. 
• Visual impressions of GI mucosal detail may 
not reflect histopathologic changes; always take 
biopsies. • Endoscopic biopsies rely upon 
infiltrative and inflammatory diseases being 
represented in first two layers of the intestinal 
wall, and segments biopsied being representative 
of disease process. • Full-thickness biopsies can 
be obtained via laparoscopy from one or more 
segments of small intestine (not large intestine) 
via exteriorization of the segment(s), but are not 
typically necessary as most diseases can be 
diagnosed endoscopically.
Surgical Biopsy
Surgical approach beneficial if biopsies of 
multiple organs (small intestine, lymph 
nodes, stomach, pancreas, liver) are desired.
Ultrasound-Guided GI Aspiration or 
Biopsy
• Can perform ultrasound-guided fine-needle 
aspiration on some GI mass lesions, but 
cytologic interpretation accuracy is subject to 
sample quality, expertise, and limitations of 
technique; small cell alimentary lymphoma 
cannot be diagnosed by cytology, as cells will be 
small lymphocytes. • Paracentesis of peritoneal 
fluid for fluid analysis, culture, and cytology is 
recommended. • Concern has been expressed 
for risk of translocation of cancer cells or 
infective organisms with these procedures.
Vary with underlying disease.
  TREATMENT
• Outpatient medical management most 
common. • T reat underlying cause.
• Give fluid therapy with balanced electrolyte 
solution as needed. • Correct electrolyte and 
acid-base imbalances.
ACTIVITY
No restriction.DIET
• Feeding elimination diet (intact novel 
protein source or hydrolyzed protein) will 
resolve diarrhea in 40–60% of cats with 
chronic enteropathy; response should be 
detected within 2–3 weeks following dietary 
implementation. • Repeated changes of diet 
made in order to maintain a symptom-free 
situation suggest that further testing needed.
Complete resolution of signs is not always 
possible in cats with IBD, neoplasia, or fungal 
disease despite proper treatment.
Pursue exploratory laparotomy and surgical 
biopsy if evidence of obstruction, intestinal 
mass, or mid-small bowel disease unreachable 
via endoscopic procedure.
• Disease specific. • Prednisolone (1–2 mg/
kg BID) for management of IBD; 
chlorambucil (2 mg/cat q48–72h) should be 
considered together with prednisolone in 
severe IBD cases that are refractory to 
steroids alone or for management of small 
cell intestinal lymphoma. • Supplementation 
with cyanocobalamin at 250 ug SC per cat 
on a weekly basis for 6 consecutive weeks, 
followed by every 3 weeks for the indefinite 
future. • Probiotics can be beneficial in 
some patients with chronic nonspecific 
diarrhea.
Anticholinergics exacerbate most types of 
chronic diarrhea and should not be used for 
empirical treatment.
Opiate antidiarrheals such as diphenoxylate 
and loperamide can cause hyperactivity and 
respiratory depression in cats and should not 
be used for more than 3 days.
N/A
N/A
  FOLLOW-UP
• Assess changes in frequency and severity of 
diarrhea and bodyweight. • Resolution 
usually occurs within 2–3 weeks following 
successful implementation of dietary therapy; 
consider reevaluating diagnosis if diarrhea 
does not resolve.
• Dehydration. • Lowered body condition. 
• Abdominal effusions as related to specific 
cause of chronic diarrhea.
N/A
N/A
• Toxoplasmosis. • Giardiasis (low zoonotic 
potential). • Cryptosporidiosis. • Salmonellosis. 
N/A
SYNONYMS
None
SEE ALSO
• Cobalamin Deficiency. • Diarrhea, Antibiotic 
Responsive. • Exocrine Pancreatic Insufficiency. 
• Food Reactions (Gastrointestinal), Adverse. 
• Inflammatory Bowel Disease. • Small 
Intestinal Dysbiosis.
• FeLV = feline leukemia virus. • FIV = feline 
immunodeficiency virus. • GI = gastrointestinal. 
• IBD = inflammatory bowel disease. • PLE 
= protein-losing enteropathy.
Evans SE, Bonczynski JJ, Broussard JD, et al. 
Comparison of endoscopic and full-thick-
ness biopsy specimens for diagnosis of 
inflammatory bowel disease and alimentary 
tract lymphoma in cats. J Am Vet Med 
Assoc 2006, 229(9):1447–1450.
Sabattini S, Bottero E, T urba ME, et al. 
Differentiating feline inflammatory bowel 
disease from alimentary lymphoma in duodenal 
endoscopic biopsies. J Small Anim Pract 2016, 
57(8):396–401. doi: 10.1111/jsap.12494
Tolbert MK, Gookin JL. T ritrichomonas foetus: 
a new agent of feline diarrhea. Compend 
Contin Educ Pract Vet 2009, 31(8):374–381.
Willard MD, Mansell J, Fosgate GT, et al. 
Effect of sample quality on the sensitivity of 
endoscopic biopsy for detecting gastric and 
duodenal lesions in dogs and cats. J Vet 
Intern Med 2008, 22(5):1084–1089.
Mark E. Hitt.
available onlineDiarrhea, Chronic—Cats  (continued)

Canine and Feline, Seventh Edition  405
DDiarrhea, Chronic—Dogs
  BASICS
volume of feces for more than 3 weeks. • Can 
be small bowel, large bowel, or mixed.
• Secretory diarrhea. • Osmotic diarrhea. 
• Increased permeability. • Abnormal 
gastrointestinal (GI) motility. • Many cases 
involve combinations of these pathophysio­
logic mechanisms.
• Endocrine/metabolic. • Exocrine. 
• Cardiovascular (fluid balance). • GI. 
• Lymphatic.
GENETICS
N/A
Unknown
Pythiosis occurs often in young, large ­breed dogs 
living in rural areas, with a higher incidence in 
states bordering the Gulf of Mexico.
Species
Dog
• Yorkshire terrier, West Highland white 
terrier, Rottweiler, soft ­coated wheaten 
terrier—lymphangiectasia secondary to 
inflammatory bowel disease (IBD). • Boxer 
and French bulldog—granulomatous colitis.
Any age.
None
SIGNS
• Disease processes determine extent of 
clinical signs. • 2–3% increase of water 
mixed bowel types of diarrhea may have 
overlap of descriptive findings.
borborygmus; vomiting—variable. • Large 
frequency of defecation increased ( >4 times/
urgency, dyschezia; flatulence and borborygmus—  
variable; vomiting—variable.
• Poor body condition associated with 
malabsorption, maldigestion, and protein ­losing enteropathy (PLE). • Variable dehydration. 
• Abdominal palpation may reveal thickened 
small bowel loops (diffuse or segmental) 
associated with infiltrative disease, abdominal 
effusion, foreign body, neoplastic mass, 
intussusception, or enlarged mesenteric lymph 
nodes. • Rectal palpation typically unremarkable.
• Body condition more typically normal. 
foreign body, neoplastic mass, intussusception, 
or enlarged mesocolic lymph nodes. • Rectal 
palpation may reveal irregularity of colorectal 
mucosa, intraluminal or extraluminal rectal 
masses, rectal stricture, or sublumbar 
lymphadenopathy.
CAUSES
Primary Small Intestinal Disease
• Inflammatory bowel disease (e.g., lympho­
plasmacytic enteritis, eosinophilic enteritis, 
granulomatous enteritis, immunoproliferative 
enteropathy of Basenjis). • Primary or secondary 
lymphangiectasia. • Neoplasia. • Bacterial 
(Campylobacter jejuni , Salmonella  spp., invasive 
adherent or enterotoxic Escherichia coli , other 
enterobacteriaceae species). • Mycotic (e.g., 
histoplasmosis). • Algal (e.g., protothecosis, 
pythiosis). • Parasites (e.g., Giardia , Toxocara  
spp., Ancylostoma , Toxascaris leonina , 
Cryptosporidium  spp., Cystoisospora  spp.). 
• Partial obstruction (e.g., foreign body, 
intussusception, neoplasia). • Antibiotic ­
responsive diarrhea (ARD; intestinal microbial 
dysbiosis). • Short bowel syndrome.
• Exocrine pancreatic insufficiency (EPI). 
• Hepatobiliary disease—lack of intraluminal bile.
Dietary
• Food ­responsive enteropathy. • Food allergy.
• Hepatobiliary disease. • Hypoadrenocorticism. 
• Uremic gastroenteritis. • Toxins—entero­
toxins, aflatoxins, exotoxins, food poisoning. 
• Adverse drug reactions.
Primary Large Intestinal Disease
plasmacytic colitis, eosinophilic colitis, 
granulomatous colitis). • Neoplasia. 
• Infection (e.g., histoplasmosis, adherent 
invasive E. coli  [granulomatous colitis], 
Prototheca , pythiosis). • Parasites (e.g., 
Trichuris vulpis , Giardia intestinalis , Entamoeba 
histolytica , Balantidium coli ). • Ileocolic 
intussusception and cecal inversion.
Dietary
• Diet—dietary indiscretion, diet changes, 
food­responsive enteropathy, foreign material 
(e.g., bones, plastic, wood, hair). • Fiber ­
responsive large bowel diarrhea.
Irritable bowel syndrome.RISK FACTORS
• Large ­breed, younger, and less severely 
affected dogs have higher risk of food ­
responsive diarrhea. • Yorkshire terrier, West 
Highland white terrier, Rottweiler, soft ­coated 
wheaten terrier predisposed to lymphang­
iectasia secondary to IBD.
• Dietary changes or indiscretion, stress, and 
psychological factors may play a role. 
• Granulomatous colitis (invasive adherent E. 
coli–associated)—boxer, French bulldog <3 
years old. • Pythiosis more common in 
large­breed dogs that spend more time 
outside (roaming, hunting).
  DIAGNOSIS
First localize the origin to the small or large 
bowel (or both).
• Eosinophilia may be associated with 
parasitism, eosinophilic enterocolitis, hypo­
adrenocorticism, paraneoplastic causes, or 
pythiosis. • Lymphopenia and hypocholestero­
lemia may be associated with lymphangiectasia. 
• Anemia and microcytosis suggest chronic GI 
bleeding and iron deficiency. • Panhypopro­
teinemia resulting from PLE associated with 
infiltrative small bowel disorders and lymphangi ­
ectasia. • Biochemical profiles and urinalysis 
hepatobiliary disease, or endocrinopathy.
• Direct wet ­prep examination, fecal ELISA 
testing, and zinc sulfate centrifugation (for 
Giardia ) may indicate GI parasites; multiple 
samples may be required for whipworm 
infestations. • Cytologic examination of rectal 
Histoplasma  or Prototheca . • PCR fecal testing 
can be helpful when screening for uncommon 
or difficult to diagnose infections; interpret 
with caution as many of the microorganisms 
can be found in healthy, nondiarrheic animals 
(e.g., viral enteritis, cryptosporidiosis, Giardia , 
Salmonella , C. perfringens  enterotoxin gene, C. 
difficile, Campylobacter jejuni ); PCR testing 
should be interpreted in light of patient 
signalment, history, clinical presentation, 
• Culture feces if Campylobacter  or Salmonella  
suspected—special media required; check with 
laboratory prior to submission.
Tests of Exocrine Pancreatic Function
Canine ­specific trypsin ­like immunoreactivity 
(TLI)—test of choice for confirming EPI.
Tests for Malabsorption
• Serum folate—low serum folate may be 
associated with proximal small intestinal 
malabsorption. • Cobalamin—low serum

406  Blackwell’s Five-Minute Veterinary Consult  
Dcobalamin may be associated with EPI or ileal 
malabsorption; primary cobalamin deficiency 
syndromes are rare (border collie, giant 
schnauzer).
Tests for Metabolic Disease
• Resting cortisol—value <2.0 μg/dL should 
be followed up with adrenocorticotrophic 
hormone stimulation test to evaluate for 
hypoadrenocorticism. • Fasting and 2 ­hour 
postprandial serum bile acids—test if 
hepatobiliary disease suspected; significantly 
increased values suggest hepatic dysfunction 
or portosystemic shunting.
IMAGING
abnormal intestinal pattern, organomegaly, mass, 
foreign body, pancreatic disease, hepatobiliary 
disease, urinary disease, or abdominal effusion. 
• Contrast radiography (upper GI series or 
barium enema) may indicate bowel wall 
thickening, intestinal ulcers, mucosal 
irregularities, mass, radiolucent foreign body, or 
stricture; utility of contrast radiography has been 
replaced with ultrasound in most patients. 
• Abdominal ultrasonography may demonstrate 
bowel wall thickening, abnormal bowel wall 
layering, GI or extra ­GI masses, intussusception, 
foreign body, ileus, abdominal effusion, hepato  ­ 
biliary disease, or mesenteric or mesocolic 
If maldigestive (EPI), metabolic, parasitic, dietary, 
and infectious causes have been excluded, then 
consider dietary trial using elimination diet 
(novel, single protein source) or hydrolyzed diet 
for 2 weeks in stable dogs prior to performing 
advanced diagnostics (endoscopy or laparotomy 
and biopsy). Up to 75% of dogs in referral 
practices have been shown to be diet responsive.
• Upper GI flexible endoscopy allows 
examination and biopsy of gastric and duodenal 
specimens from each segment. • Flexible 
colonoscopy allows examination of rectum, 
colon, cecum, and ileum; always obtain 
multiple mucosal specimens (8–10) from each 
segment. • Gross appearance of mucosa does 
not always correlate with histopathology; always 
take biopsies. • Endoscopic biopsies rely upon 
diseases being represented in first two layers of 
intestinal wall and segments biopsied being 
representative of others not reached. • Full­
thickness biopsies not indicated as most diseases 
can be diagnosed endoscopically. • Surgical 
approach can be advantageous if biopsies of 
multiple organs (e.g., small intestine, lymph 
nodes, stomach, pancreas, liver) are desired
Ultrasound-Guided GI Aspirates
• Ultrasound ­guided fine ­needle aspiration of GI 
mass lesions can be helpful for diagnosing mast 
cell tumors, carcinomas, and large ­cell lymphoma. 
• Seeding of neoplastic cells is a concern.
Capsule Endoscopy
Capsule endoscopy procedures can help identify 
location of bleeding ulcers in the jejunum.  TREATMENT
• Fluid therapy with balanced electrolyte 
solutions as needed. • Correct electrolyte and 
acid­base imbalances.
ACTIVITY
No restrictions.
DIET
• Therapy with elimination diets or hydrolyzed 
diets can be beneficial in up to 75% of dogs 
with uncomplicated chronic enteropathies. 
• Feeding lower ­fat, novel (for the patient) 
protein source, highly digestible, or fiber ­
supplemented diets for 3–4 weeks may resolve 
diarrhea due to dietary intolerance or allergy; 
repeated changes of diet to maintain symptom ­
free situation suggests further testing needed.
possible in dogs with severe IBD, lymphangi­
ectasia, intestinal neoplasia, and pythiosis.
Pursue laparotomy and biopsy if evidence of 
obstruction, intestinal mass, or mid ­small bowel 
disease unreachable via ultrasound ­guided 
procedure, or if diagnosis based on endoscopic 
biopsy or ultrasound ­guided procedure is 
questioned because of poor response to therapy.
• Disease ­specific. • Prednisone (2 mg/kg BID for 
2 weeks, with slow tapering over 6 weeks) for IBD. 
• Cyclosporine has shown to rescue dogs with 
steroid ­refractory IBD. • Need for cyanocobala ­
min supplementation must be assessed in all dogs 
with chronic enteropathy. • Probiotics beneficial in 
some dogs with chronic enteropathy.
Anticholinergics can exacerbate the situation 
with many causes of chronic diarrhea; they 
are sometimes used to relieve cramping 
associated with irritable bowel syndrome.
N/A
N/A
N/A
  FOLLOW-UP
• Frequency and consistency of stool, 
appetite, and bodyweight. • In dogs with PLE—serum proteins, cholesterol, and 
clinical signs (ascites, subcutaneous edema, 
pleural effusion). • Resolution of diarrhea 
usually gradual with treatment; if does not 
resolve, reevaluate diagnosis.
N/A
cause of chronic diarrhea. • Ascites, subcutan  ­ 
eous edema, and/or pleural effusion with 
hypoalbuminemia from PLE.
N/A
N/A
• Giardiasis (low risk of transmission). 
• Salmonellosis. • Campylobacter jejuni . 
• Ascaridiasis.
N/A
SYNONYMS
N/A
SEE ALSO
• Colitis, Histiocytic Ulcerative. • Diarrhea, 
Antibiotic Responsive. • Fiber ­Responsive 
Large Bowel Diarrhea. • Food Reactions 
(Gastrointestinal), Adverse. • Inflammatory 
Bowel Disease. • Lymphangiectasia. • Protein ­
Losing Enteropathy. • Small Intestinal Dysbiosis.
• ARD = antibiotic ­responsive diarrhea.  
• EPI = exocrine pancreatic insufficiency.  
• GI = gastrointestinal. • IBD = inflammatory 
bowel disease. • PLE = protein ­losing 
enteropathy. • TLI = trypsin ­like immuno  ­ 
reactivity.
Long ­term outcome in dogs with chronic 
available onlineDiarrhea, Chronic—Dogs  (continued)

Canine and Feline, Seventh Edition  407
DDigoxin Toxicity
  BASICS
OVERVIEW
Not uncommon in patients treated with 
digoxin due to digoxin’s narrow therapeutic 
index and prevalence of renal impairment in 
elderly patients with cardiac disease. Becoming 
less common in clinical practice as use of 
digoxin has decreased in management of 
heart failure.
• More common in geriatric patients.
SIGNS
Heart rate may range from severe bradycardia 
to severe tachycardia.
• Renal disease—impairs digoxin elimination.
• Chronic pulmonary disease—results in 
hypoxia and acid-base disturbances.
• Obesity—if dosage not calculated on lean 
bodyweight.
• Drugs and conditions that alter digoxin 
metabolism or elimination (e.g., quinidine 
and hypothyroidism).
• Rapid IV digitalization.
• Overdosage or accidental ingestion of 
owner’s medication.
• Administration of diuretic leading to 
  DIAGNOSIS
• Arrhythmias and conduction distur-
bances—may reflect structural heart disease, 
not digoxin toxicity.
• Anorexia—common in animals with heart 
failure.
Animals with hypokalemia, hypercalcemia, 
hypomagnesemia, and renal failure are 
predisposed to toxicity.
• Consider checking thyroid status.
• Obtain digoxin serum concentration 8–10 
hours after an oral dose—therapeutic range is 
0.5–1.5 ng/mL. A recent study in humans 
found digoxin levels greater than 1 mg/ml 
were associated with increased mortality; not all patients with concentrations >1.5 ng/mL 
have signs of toxicity; some with values in the 
normal range have signs of toxicity, especially 
if hypokalemic. To minimize the risk of 
toxicity, the author aims to achieve a digoxin 
level between 0.5 and 1 ng/mL.
IMAGING
N/A
ECG
• Conduction disturbances—atrioventricular 
(AV) block, arrhythmias, and ST segment 
depression in some patients.
• Digoxin can cause any arrhythmia.
  TREATMENT
• Discontinue digoxin until signs of toxicity 
resolve (24–72 hours); reevaluate need for the 
medication; if necessary, resume treatment at 
a dosage based on the serum digoxin concen- 
tration.
• Maintain hydration and correct any 
electrolyte disturbance (especially hypoka-
lemia) with parenteral fluid administration.
• Discontinue drugs that slow digoxin 
metabolism or elimination (e.g., quinidine, 
verapamil, amiodarone).
• Severe arrhythmias (ventricular tachycardia) 
and conduction disturbances—can be life- 
threatening; require hospitalization for 
treatment and monitoring.
• T reat clinically important bradyarrhythmias 
with atropine or a temporary transvenous 
pacemaker.
• T reat clinically important ventricular 
arrhythmias with lidocaine or phenytoin; 
phenytoin also reverses high-degree AV block.
• Digoxin-binding antibodies (e.g., Digibind®) 
rapidly drop digoxin concentration in critically 
ill animals; the use of these products is limited 
in veterinary practice by their exorbitant cost.
• Thyroxin supplementation if hypothyroid-
ism confirmed.
• Avoid or discontinue drugs that slow 
digoxin elimination or metabolism (e.g., 
quinidine, verapamil, and diltiazem).
• Avoid drugs that could worsen conduction 
disturbances (e.g., beta blockers and calcium 
channel blockers).
• Class 1A antiarrhythmic drugs (e.g., quinidine 
and procainamide) may worsen AV block.  FOLLOW-UP
• Inform owner that reduction in appetite is 
an early indication of digoxin toxicity.
• Monitor renal function and electrolytes 
frequently in patients receiving digoxin; lower 
digoxin dose if renal disease develops.
• Monitor serum digoxin concentration 
periodically.
• Monitor ECG periodically to assess for 
arrhythmias or conduction disturbances that 
may suggest digoxin toxicity.
• Monitor bodyweight frequently; alter 
digoxin dosage accordingly; patients with 
congestive heart failure often lose weight.
SEE ALSO
Degree).
Teerlink JR, Gersh BJ, Opie LH. Heart 
failure. In: Opie LH, Gersh BJ, eds., Drugs 
for the Heart, 8th ed. Philadelphia, PA: 
Elsevier Saunders, 2013, pp. 169–223.

408  Blackwell’s Five-Minute Veterinary Consult  
DDiisocyanate Glues
  BASICS
OVERVIEW
• Diisocyanate glues include wood glue, 
construction glue, and some “high-strength 
or extra strength” glues.
• Gorilla Glue is one popular brand name. 
There are non-Gorilla brand glue types that 
contain diisocyanate as the active ingredient 
and not all types of Gorilla Glue contain 
diisocyanates. Confirm the actual product 
with the owner, using the packaging if 
• Typically, the owner finds a chewed bottle 
of glue or glue stuck on the animal.
• Diisocyanate glue rapidly expands in the 
moist environment of the stomach, causing 
bloat and foreign body obstruction (FBO). 
The glue is not absorbed and does not cause 
systemic toxicity. Ingestions as small as 2 oz 
(56 g) can require surgical intervention to 
resolve obstruction.
• Glue is also adhesive and an irritant to the 
paws, oral cavity, and stomach lining.
• Inhalation may cause irritation to the  
lungs.
Dogs and less commonly cats, birds, and 
small mammals. Young animals are more 
often affected.
SIGNS
• Occur within 15 minutes to 24 hours after 
ingestion.
• Ingestion—consistent with FBO and may 
include gagging, retching, vomiting, anorexia, 
abdominal distension, abdominal pain; 
hematemesis in prolonged or severe cases.
• Inhalation—coughing, sneezing, increased 
secretions within 4–8 hours.
• Dermal—irritation, redness, rash.
Pets with access to diisocyanate glue products.
  DIAGNOSIS
• History of exposure and clinical signs 
generally facilitate diagnosis.
• Presenting signs are consistent with gastric 
dilatation-volvulus (GDV), bloat, pancreatitis,  
inflammatory bowel disease, and other causes 
of FBO.
• Radiographs are highly suggestive of FBO 
(see Web Figure 1).
• CBC—generally no significant changes.
• Electrolyte disturbances—consistent with 
gastrointestinal (GI) obstruction and 
anorexia.• Elevated total proteins/prerenal azotemia—
may occur secondary to dehydration from 
vomiting.
IMAGING
Survey radiographs (4–24 hours post 
exposure)—glue appears as a mottled gas and 
soft tissue opacity distending the stomach. 
The appearance can resemble recent food 
ingestion (see Web Figure 1).
  TREATMENT
• Generally, not recommended due to risk 
of esophageal or GI obstruction. Potential 
use immediately after a large ingestion.
• Gastric lavage is rarely of benefit as glue 
expands too rapidly.
• Dilution with water or other fluids should 
be avoided as excess moisture allows further 
expansion of the glue.
• IV fluids as needed for dehydration.
• Wash exposed skin with warm soapy water, 
rub vegetable oil into the hair, or clip hair to 
remove as much glue as possible. Glue can be 
left adhered to the skin if nonirritating and 
will fall off over time.
• Oxygen as needed for signs related to 
inhalation.
• Surgical removal of the expanded glue 
foreign body is almost always indicated in 
ingestions greater than 2 oz or with lesser 
amounts in smaller animals.
• Antiemetic—maropitant citrate 1 mg/kg 
SC/IV q24h.
• H2 blocker (for gastric inflammation or 
ulceration)—ranitidine 1–2 mg/kg PO/IM/
SC/IV q6–12h; famotidine 0.5–1.1 mg/kg 
PO q12h; pantoprazole 0.7–1 mg/kg IV over 
15 minutes q24h.
• Sucralfate (for a gastric ulcer if present)— 
0.5–1 g PO TID on an empty stomach.
unless done immediately after a witnessed 
ingestion. Expansion of the glue is rapid: late 
emesis stresses the stomach wall and could 
damage the esophagus.
• Do not dilute with water as exposure to 
moisture leads to rapid expansion of the glue.
  FOLLOW-UP
Monitor in hospital until eating and drinking 
normally. Recheck 10–14 days post surgery.PREVENTION/AVOIDANCE
Prevent exposure.
• With removal of FBO, prognosis is 
excellent.
• Without surgical removal, the FBO is not 
expected to resolve on its own.
• Gastritis.
• Dermatitis.
• GDV = gastric dilatation-volvulus.
Horstman CL, Eubig PA, Cornell KK, et al. 
Gastric outflow obstruction after ingestion 
of wood glue in a dog. J Am Anim Hosp 
Assoc 2003, 39:47–51.
Peterson KL. Glues and adhesives. In: Hovda 
LR, Brutlag A, Poppenga R, Peterson K, 
eds., Blackwell’s Five Minute Veterinary 
Consult: Small Animal Toxicology, 2nd ed. 
Ames, IA: Wiley-Blackwell, 2016, pp. 
95–100.
Acknowledgment:  The author and book 

Canine and Feline, Seventh Edition  409
DDiscolored Tooth/Teeth
  BASICS
• Normal tooth color varies and depends on 
the shade, translucency, and thickness of 
enamel. T ranslucent enamel is bluish-white, 
opaque enamel is gray-white.
• Extrinsic—from surface accumulation of 
exogenous pigment.
• Intrinsic—secondary to endogenous factors 
discoloring the underlying dentin.
Extrinsic Discoloration
• Bacterial stains—chromogenic bacteria: 
green to black-brown to orange color, usually 
1 mm above the gingival margin on the tooth.
• Plaque related—a black-brown stain; 
usually secondary to the formation of ferric 
sulfide from the interaction of bacterial ferric 
sulfide and iron in the saliva. Plaque is usually 
white.
• Foods—charcoal biscuits and similar 
products penetrate the pits and fissures of the 
enamel; food with abundant chlorophyll can 
produce a green discoloration.
• Gingival hemorrhage—green or black 
staining from the breakdown of hemoglobin 
into green biliverdin.
• Dental restorative materials—amalgam: 
black-gray discoloration.
• Medications—products containing iron or 
iodine give a black discoloration; sulfides, 
silver nitrate, or manganese: gray-to-yellow to 
brown-to-black discoloration; copper or 
nickel: green discoloration; cadmium, yellow 
to golden brown discoloration (e.g., 8% 
stannous fluoride combines with bacterial 
sulfides, giving a black stain; chlorhexidine 
gives a yellowish-brown discoloration).
• Metals—wear from chewing on cages or 
food dishes.
• From removed orthodontic brackets or 
bands.
• Crown fragments—less translucency due to 
dehydration of fragment.
• Discolored restorations.
• Tooth wear with dentin exposure—tertiary 
dentin, reparative dentin, secondary dentin.
• A calculus-covered crown ranges in color 
from dark yellow to dark brown.
Intrinsic Discoloration
• Hyperbilirubinemia—affects all teeth; 
during dentin formation bilirubin accumulates 
in the dentin from excess red blood cell 
breakdown; extent of discoloration depends 
on the length of hyperbilirubinemia (lines of 
resolution occur once the condition has been 
resolved); green discoloration.
• Localized red blood cell destruction, one 
tooth or focal area—usually follows a 
traumatic injury to the tooth; discoloration 
from hemoglobin breakdown within the pulp with release into adjacent dentinal tubules; 
discoloration goes from pink to purple 
(pulpitis) to gray (pulpal necrosis) to black 
(liquefactive necrosis).
• Amelogenesis imperfecta—developmental 
alteration in the structure of enamel affecting 
all teeth; chalky appearance with a pinkish 
hue; problem in the formation of the organic 
matrix, mineralization of the matrix, or the 
maturation of the matrix.
• Dentinogenesis imperfecta—developmental 
alteration in dentin formation; enamel 
separates easily from the dentin, resulting in 
grayish discoloration.
• Infectious agents (systemic)—parvovirus, 
distemper virus, or any agent that causes a 
sustained body temperature rise; affects the 
formation of enamel; a distinct line of 
resolution is visible on the teeth; affects all 
teeth developing at the time of the insult; 
results in enamel hypoplasia or hypocalcifica-
tion where the abnormal enamel can have 
black edges and the dentin is brownish.
• Dental fluorosis—affects all teeth; excess 
fluoride consumption affects the maturation 
of enamel, resulting in pits (enamel hypo-
plasia) with black edges; the enamel is a 
lusterless, opaque white, with yellow-brown 
zones of discoloration.
• Tooth erosion from constant vomiting 
results in enamel pitting and darkened 
staining.
• Attrition—tooth-to-tooth wear results in 
crown loss and reparative dentin formation 
(yellow-brown color).
• Abrasion—tooth wear against another 
surface; chewing on tennis balls or from a 
dermatologic condition. Reparative dentin 
(yellow-brown color) forms.
• Aging—older animals’ dentition is more 
yellow and less translucent.
• Malnutrition (generalized, vitamin D 
deficiency, and vitamin A deficiency)—if 
severe can result in demarcated opacities on 
the enamel.
Internal/External Resorption
• Internal—follows pulpal injury (trauma) 
causing vascular changes with increased 
oxygen tension and decreased pH, resulting 
in destruction (resorption) of the tooth from 
within the pulp from odontoclasts; tooth has 
pinkish hue.
• External—many factors possible: trauma, 
orthodontic treatment, excessive occlusal 
forces, periodontal disease (and treatment), 
tumors, periapical inflammation, and 
unknown factors; resorption can start 
anywhere along the periodontal ligament and 
can extend to the pulp and into the crown 
causing a pinkish discoloration; osteoclasts 
and odontoclasts resorb the tooth structure.
Medications and Discoloration
• Tetracycline—during enamel formation, it 
binds to calcium, forming a calcium orthophosphate complex in the collagen 
matrix of enamel; occurs on multiple teeth; 
results in a yellow-brown discoloration. 
Long-term use of tetracyclines in mature 
animals can involve secondary dentin 
• Amalgam (as with extrinsic stains).
• Iodine/essential oils.
• In endodontically treated teeth from the 
medicants penetrating the dentinal tubules.
• Macrolide antibiotic (reported in humans)—  
results in vacuolar degeneration of the 
ameloblast and cystic change at maturation 
and hypocalcification, giving a white 
discolored lesion with horizontal stripes on 
• Bacterial “creeping” (leakage)—occurs 
around the margins of a restoration and 
usually is blackish in color.
Gastrointestinal—oral cavity.
GENETICS
• Amelogenesis imperfecta and dentinogenesis 
imperfecta in humans are inherited conditions 
that have many modes of inheritance. The 
mode of inheritance in animals has not been 
studied.
• Congenital hypothyroidism.
• Metabolic diseases.
• Discoloration of the teeth or a tooth is 
extremely common in all animals.
• Extrinsic staining is very common, 
especially bacterial stains; others are less 
common.
• Intrinsic staining is likewise very common, 
especially internal and external resorption, 
followed by localized red blood cell destruc-
tion; the other causes are rare.
• Heavy metals from mining operations.
• Fluoridation forms areas of excessive 
fluoride in the drinking water.
• Otherwise none.
Species
The reported age range varies—when the 
condition affects the developing enamel or 
dentin it can be first noted after tooth 
eruption (6 months of age).
None
SIGNS
Owner reports a variation in color of a tooth 
or teeth.
• Abnormal coloration of tooth or teeth.
• Pitted enamel with staining.

410  Blackwell’s Five-Minute Veterinary Consult  
D• Fractured tooth.
• Rings or lines of discoloration around tooth 
or teeth.
• Wear on crowns of the dentition or in 
selected areas as in behavioral causes (cage 
biters—distal aspect of the canines is 
• Erosion of enamel.
• Extrinsic discoloration—bacterial stains 
from plaque and calculus; foods; gingival 
hemorrhage; dental restorative materials, 
medications (chlorhexidine, 8% stannous 
fluoride), metal.
• Intrinsic discoloration—internal (trauma); 
external tooth resorption; localized red blood 
cell destruction in the tooth (trauma); 
systemic infections; medications (tetracy-
cline); fluorosis; hyperbilirubinemia; 
amelogenesis imperfecta; dentinogenesis 
imperfecta.
  DIAGNOSIS
• Calculus on the teeth.
• Normal tooth aging—increased 
translucence.
• Food debris lodged in the spaces between 
the teeth (diastema).
• Anemia—blood-related disorders.
• Bilirubin—increased with liver diseases.
• T3/T4—low in congenital hypothyroidism.
• Specific metabolic enzyme decrease or 
absence—tyrosinemia.
IMAGING
Dental radiography is extremely useful in 
identifying internal or external resorption, 
restorative materials, or bacterial stain from 
coronal percolation.
• If many teeth are affected, one tooth can be 
extracted and sent for histologic evaluation 
(see below).
• T ransillumination with a strong fiberoptic 
light may help distinguish between vital and 
necrotic pulp.• Appropriate preoperative diagnostics when 
indicated prior to procedure.
  TREATMENT
• Extrinsic stain removal—mainly cosmetic.
• Intrinsic stain treatment—functional and 
pain relieving.
• Extrinsic stain—remove inciting cause.
• Intrinsic stain—soft food; remove chew 
toys.
ACTIVITY
Curtail or treat specific behavioral abnormali-
ties (cage biting).
DIET
N/A
• To prevent it in future animals or litters if 
preventable (medication use).
• Intrinsic causes—irregular enamel surfaces are 
more likely to accumulate plaque and calculus, 
leading to subsequent periodontal disease.  
Abnormally formed teeth or teeth that have  
localized red blood cell destruction are more 
prone to fracture or development of tooth 
abscessation.
• Some causes are painful (tooth resorption).
• Extrinsic stain (cosmetic)—internal and/or 
external bleaching; veneers or crowns. 
Polishing the affected teeth with 3% 
hydrogen peroxide in pumice will help 
remove external stain. Also good home care 
with plaque control will minimize 
redevelopment of some stains (plaque/
calculus/bacteria stain).
• Intrinsic stain (functional and pain 
relief)—possible endodontic treatment 
(internal resorption and localized red blood 
cell destruction).
• Restorative procedures such as crowns or 
veneers to protect both tooth and pulp.
• Extraction of affected teeth may be 
required, especially with external resorption.  MEDICATIONS
N/A
  FOLLOW-UP
• See Pathophysiology.
• Good oral care at home will help prevent 
the reoccurrence of certain specific stains.
See Client Education.
Vary dependent upon the etiology, but can 
range from mere aesthetics to significant pain.
• Enamel hypoplasia/hypocalcification
• Juvenile purpura.
All ages affected, depends on the cause.
None.
• Tetracycline administration during 
pregnancy may result in permanent tooth 
discoloration in offspring.
• See Genetics.
SYNONYMS
• Chlorhexidine staining.
• Extrinsic staining.
• Intrinsic staining.
• Tetracycline staining.
Hale FA. Localized intrinsic staining of teeth 
due to pulpitis and pulp necrosis in dogs. 
J Vet Dent, 2001, 18(1):14–20.
Lobprise HB, Dodd JR. Wiggs’ Veterinary 
Dentistry Principles and Practice. Hoboken, 
NJ: Wiley-Blackwell, 2019.
Author  Kristin M. Bannon
Consulting Editor  Heidi B. LobpriseDiscolored Tooth/Teeth  (continued)

Canine and Feline, Seventh Edition  411
D
Discospondylitis
  BASICS
A bacterial, fungal, and rarely algal infection 
of the intervertebral end plates, discs, and 
adjacent vertebral bodies.
• Hematogenous spread of bacterial or fungal 
organisms—most common cause.
• Seeding secondary to migrating foreign 
body (grass awn) is also reported.
• Neurologic dysfunction—may occur; 
usually the result of spinal cord compression 
caused by proliferation of bone and fibrous 
tissue; less commonly owing to luxation or 
pathologic fracture of the spine, epidural 
abscess, or extension of infection to the 
meninges and spinal cord.
• Musculoskeletal—infection and 
inflammation of the spine.
• Nervous—compression and/or infection of 
the spinal cord.
GENETICS
• No definite predisposition identified.
• An inherited immunodeficiency has been 
detected in a few cases.
Approximately 0.1–0.8% of dog hospital 
admissions.
• More common in the southeastern United 
States.
• Grass awn migration and coccidiomycosis—  
more common in certain regions.
Species
Dog; rare in cat.
Large and giant breeds, especially German 
shepherd and Great Dane.
• Mean age—4–5 years.
• Range—5 months–12 years.
Males outnumber females by ~2 : 1.
SIGNS
• Onset usually relatively acute; however, 
some patients may have mild signs for 
several months before presenting for 
• Pain—difficulty rising, reluctance to jump, 
and stilted gait are most common signs.
• Ataxia or paresis.
• Weight loss and anorexia.
• Lameness.Physical Examination Findings
• Focal or multifocal areas of spinal pain in 
>80% of patients.
• Any disc space may be affected; lumbo  sacral 
space is most commonly involved.
• Paresis or paralysis, especially in chronic, 
untreated cases.
• Fever in ~30% of patients.
CAUSES
• Bacterial— Staphylococcus pseudintermedius  
is most common. Others include Streptococcus , 
Brucella canis , and Escherichia coli , but 
virtually any bacteria can be causative.
• Fungal— Aspergillus , Paecilomyces , 
Scedosporium apiospermum , and Coccidioides 
immitis .
• Grass awn migration is often associated 
with mixed infections, especially Actinomyces ; 
tends to affect the L2–L4 disc spaces and 
• Other causes—surgery, bite wounds.
• Urinary tract infection; reproductive tract 
• Periodontal disease.
• Immunodeficiency.
• Recent steroid administration.
• Intact male status.
  DIAGNOSIS
• Intervertebral disc protrusion—may cause 
similar clinical signs; differentiated on the 
basis of radiography and myelography.
• Vertebral fracture or luxation—detected on 
• Vertebral neoplasia—usually does not affect 
adjacent vertebral end plates.
• Spondylosis deformans—rarely causes 
clinical signs; has similar radiographic 
features, including sclerosis, ventral spur 
formation, and collapse of the disc space; 
rarely causes lysis of the vertebral end plates.
• Focal meningomyelitis—often identified by 
cerebrospinal fluid (CSF) analysis.
• Hemogram—often normal; may see 
leukocytosis.
• Urinalysis—may reveal pyuria and/or 
bacteriuria with concurrent urinary tract 
• Aerobic, anaerobic, and fungal blood 
cultures identify the causative organism in 
about 35% of cases; obtain if available.
• Sensitivity testing—indicated if cultures are 
positive.• Urine cultures—indicated; positive in about 
30% of patients.
• Organisms other than Staphylococcus  
spp.—may not be the cause.
• Serologic testing for Brucella canis —
indicated as this presents zoonotic potential.
IMAGING
• Spinal radiography—usually reveals lysis of 
vertebral end plates adjacent to the affected 
disc, collapse of the disc space, and varying 
degrees of sclerosis of the end plates and 
ventral spur formation; may not see lesions 
until 3–4 weeks after infection (therefore 
normal radiographs do not rule out).
• Myelography—indicated with substantial 
neurologic deficits; determine location and 
degree of spinal cord compression, especially 
if considering decompressive surgery; spinal 
cord compression caused by discospondylitis 
typically displays an extradural pattern.
• CT or MRI—more sensitive than radio  - 
graphy; indicated when radiographs are 
normal or inconclusive.
• CSF analysis—occasionally indicated to 
rule out meningomyelitis; usually normal or 
reveals mildly high protein.
• Bone scintigraphy—occasionally useful for 
detecting early lesions; helps clarify if 
radiographic changes are infectious or 
degenerative (spondylosis deformans).
• Fluoroscopically guided fine-needle 
aspiration of the disc—valuable for obtaining 
tissue for culture when blood and urine 
cultures are negative and there is no improve-
ment with empiric antibiotic therapy.
• Gross—loss of normal disc space; bony 
proliferation of adjacent vertebrae.
• Microscopic—fibrosing pyogranulomatous 
destruction of the disc and vertebral bodies.
  TREATMENT
• Outpatient—mild pain managed with 
• Inpatient—severe pain or progressive 
neurologic deficits require intensive care and 
monitoring.
Nonambulatory patients—keep on clean, dry, 
well-padded surface to prevent decubital 
ACTIVITY
• Explain that observation of response to 
treatment is very important in determining 
the need for further diagnostic or therapeutic 

412  Blackwell’s Five-Minute Veterinary Consult  
D• Instruct the client to immediately contact 
the veterinarian if clinical signs progress or 
recur or if neurologic deficits develop.
• Curettage of a single affected disc space—
occasionally necessary for patients that are 
refractory to antibiotic therapy.
• Goals—remove infected tissue; obtain 
tissue for culture and histologic evaluation.
• Decompression of the spinal cord by 
hemilaminectomy or dorsal laminectomy—
indicated for substantial neurologic deficits 
and spinal cord compression evident on MRI 
or myelography when there is no improve-
ment with antibiotic therapy; also perform 
curettage of the infected disc space; it may be 
necessary to perform surgical stabilization if 
more than one articular facet is removed from 
a disc site.
• Selection based on results of blood cultures 
and serology or end plate aspirate culture and 
• Negative culture and serology—assume 
causative organism is Staphylococcus  spp.; treat 
with a cephalosporin (e.g., cephalexin 22 mg/kg 
PO q8h) for 8–12 weeks.
• Acutely progressive signs or substantial 
neurologic deficits—initially treated with 
parenteral antibiotics (e.g., cefazolin; dogs 
and cats: 22 mg/kg IV q8h).
• Brucellosis—treated with tetracycline (dogs: 
15 mg/kg PO q8h) and streptomycin (dogs: 
3.4 mg/kg IM q24h) or enrofloxacin (dogs: 
10 mg/kg PO q24h).
• One study suggested that antibiosis be 
continued until radiographic signs were 
resolved (range of 40–80 weeks). The roll of 
imaging in definitively determining length of 
treatment has not been proven, however.
• Signs of severe pain—treated with an 
analgesic (e.g., oxymorphone; dogs: 0.05–
0.2 mg/kg IV/IM/SC q4–6h).
• Taper dosage after 3–5 days to gauge 
effectiveness of antibiotic therapy.
Glucocorticoids
Use nonsteroidal anti-inflammatory drugs 
(NSAIDs) and other analgesics cautiously—
may cause temporary resolution of clinical 
signs even when infection is progressing; 
when used, discontinue after 3–5 days to 
assess efficacy of antibiotic therapy.
NoneALTERNATIVE DRUG(S)
• Initial therapy—cephradine (dogs: 20 mg/kg  
PO q8h); amoxicillin trihydrate/clavulanate 
potassium (dogs: 13.75–22 mg/kg PO q12h).
• Refractory patients—clindamycin (dogs 
and cats: 10 mg/kg PO q12h), enrofloxacin 
(dogs: 10 mg/kg PO q24h; cats: 5 mg/kg PO 
q24h), orbifloxacin (dogs and cats: 2.5–
7.5 mg/kg PO q24h).
  FOLLOW-UP
• Reevaluate after 5 days of therapy.
• No improvement in pain, fever, or 
appetite—reassess therapy; consider a 
different antibiotic, percutaneous 
aspiration of the affected disc space, 
or surgery.
• Improvement—evaluate clinically and 
radiographically every 4 weeks.
and prompt diagnosis and treatment—help 
reduce progression of clinical symptoms and 
neurologic deterioration.
• Spinal cord compression owing to 
proliferative bony and fibrous tissue.
• Vertebral fracture or luxation.
• Meningitis or meningomyelitis.
• Epidural abscess.
EXPECTED COURSE  
• Recurrence is common if antibiotic therapy 
is stopped prematurely (before 8–12 weeks of 
• Some patients require prolonged therapy 
(1 year or more).
• Prognosis—depends on causative organism 
and degree of spinal cord damage.
• Mild or no neurologic dysfunction 
(dogs)—usually respond within 5 days of 
starting antibiotic therapy.
• Substantial paresis or paralysis (dogs)—
prognosis guarded; may note gradual 
resolution of neurologic dysfunction after 
several weeks of therapy; treatment 
warranted.
• Brucella canis —signs usually resolve with 
therapy; infection may not be eradicated; 
recurrence common.
See Risk Factors.
N/AZOONOTIC POTENTIAL
Brucella canis —human infection uncommon 
but may occur.
N/A
SYNONYMS
• Diskitis.
• Intervertebral disc infection.
• Intradiskal osteomyelitis.
• Vertebral osteomyelitis.
SEE ALSO
Brucellosis
drug.
Ameel L, Martlè V, Gielen I, et al. 
Discospondylitis in the dog: a retrospective 
study of 18 cases. Vlaams Diergeneeskundig 
Tijdschrift 2009, 78(5):347–353.
Bagley RS. Diskospondylitis. Fundam Clin 
Neuro 2005, 172–173(283–285):346.
Braund KG, Sharp NJH. Discospondylitis. In: 
Vite C, ed., Braund’s Clinical Neurology in 
Small Animals: Localisation, Diagnosis and 
T reatment. Ithaca, NY: IVIS, 2003. https://
www.ivis.org/library/braunds-clinical-
neurology-small-animals-localization-
diagnosis-and-treatment/degenerative
Burkert BA, Kerwin SC, Hosgood GL, et al. 
Signalment and clinical features of 
diskospondylitis in dogs: 513 cases 
(1980–2001). J Am Vet Med Assoc 2005, 
227(2):268–275.
Fischer A, Mahaffey MB, Oliver JE. 
Fluoroscopically guided percutaneous disk 
aspiration in 10 dogs with diskospondylitis. 
J Vet Intern Med 1997, 11:284–287.
Johnson RG, Prata RG. Intradiskal osteomy-
elitis: a conservative approach. JAAHA 
1983, 19:743–750.
Kerwin SC, Lewis DD, Hribernik TN, et al. 
Diskospondylitis associated with Brucella 
canis infection in dogs: 14 cases (1989–
1991). J Am Vet Med Assoc 1992, 
201:1253–1257.
Kornegay JN. Diskospondylitis. In: Kirk RW, ed., 
Current Veterinary Therapy IX. Philadelphia, 
PA: Saunders, 1986, pp. 810–814.
Ruoff CM, Kerwin SC, Taylor AR. 
Diagnostic imaging of discospondylitis. Vet 
Clin North Am Small Anim Pract 2018, 
48:85–94.
Thomas WB. Diskospondylitis and other 
vertebral infections. Vet Clin North Am 
Small Anim Pract 2000, 30:169–182.
available onlineDiscospondylitis  (continued)

Canine and Feline, Seventh Edition  413
D
Disseminated Intravascular Coagulation
  BASICS
An acquired complex hemostatic defect 
arising from a variety of inciting causes that 
leads to intravascular activation of coagula-
tion and consumption of clotting factors. It 
results in widespread formation of micro-
thrombi with clinical manifestations of 
thrombosis and/or hemorrhage. Non-overt 
is the early, compensated form of DIC that 
features consumption of coagulation factors 
and generation of microthrombi without clear 
clinical signs. Overt (decompensated) DIC 
refers to the classic phenotype associated with 
hemorrhage, thrombosis, and organ failure.
• DIC represents a complication of a variety 
of primary conditions. It begins with a 
hypercoagulable state that leads to production 
or embolization of microthrombi in small 
vessels.
• The primary conditions act through 
increased exposure/production of tissue factor 
(TF) that activates the extrinsic coagulation 
pathway.
• TF is normally restricted from intravascular 
exposure. Increased TF exposure occurs 
through widespread endothelial injury and/or 
• Inflammation activates endothelial cells, 
platelets, and monocytes leading to membrane 
expression of TF . Inflammatory cytokines also 
induce vesiculation of these membranes, 
releasing large quantities of microparticles 
into circulation that are enriched with both 
TF and phosphatidylserine (PS) and facilitate 
initiation of coagulation. Some neoplastic 
cells constitutively produce membrane TF 
and also release microparticles.
• Microparticles provide a suitable membrane 
surface for amplifying intrinsic and common 
pathway coagulation, potentially leading to 
uncontrolled production of thrombin that 
overwhelms endogenous coagulation inhibitors. 
Fibrin clots generated by thrombin can cause 
vascular occlusion and lead to organ 
• Widespread microthrombus formation 
consumes coagulation factors and platelets 
while initiating fibrinolysis. By-products of 
fibrinolysis (fibrin degradation products 
[FDPs]) have anticoagulant properties and 
inhibit platelet function. Hemorrhage at a 
variety of sites can follow.
• Uncontrolled progression leads to 
widespread tissue hypoxia, multiorgan 
dysfunction, and death.
Multisystemic syndrome.INCIDENCE/PREVALENCE
Associated with severe systemic inflammatory 
disease.
Species
Dogs and cats; diagnosed more in dogs.
None
Depends on the primary disease.
None
SIGNS
• Vary with the primary disease and with 
DIC-associated organ dysfunction.
• Petechiae.
• Bleeding from venipuncture sites, mucosa, 
or into body cavities.
• Bleeding is infrequent in cats, possibly 
leading to underdiagnosis.
CAUSES
• Gastric dilatation-volvulus.
• Heat stroke.
• Hemolysis, especially immune mediated.
• Hemorrhagic gastroenteritis.
• Infectious diseases, systemic (especially 
endotoxemia).
• Inflammation, severe—regardless of 
• Liver disease, severe.
• Malignancies, especially hemangiosarcoma, 
mammary carcinoma, and pulmonary 
adenocarcinoma in dogs and lymphoma in cats.
• Protein-losing nephropathy.
• Shock, hypoxia, acidosis.
• Thrombocytopenia, especially immune- 
mediated.
• T ransfusion incompatibility.
• T rauma.
• Envenomation.
  DIAGNOSIS
• Key differentials—immune-mediated 
thrombocytopenia, anticoagulant toxicity, 
coagulation factor deficiency, paraproteinemia.
• Highly variable diagnostic pattern includes 
thrombocytopenia, prolonged clotting times 
(prothrombin time [PT], activated partial 
thromboplastin time [APTT]), decreased 
fibrinogen, decreased antithrombin (AT), and 
increased products of fibrinolysis (FDPs, 
D-dimers).• Suspect DIC any time thrombocytopenia 
and prolonged clotting tests are seen 
together.
• Patients showing predisposing conditions 
should have laboratory monitoring every 
24–48 hours. A sudden drop in platelet count 
and a 20–30% prolongation in APTT is 
suspicious for non-overt DIC. This is a 
critical stage for intervention to prevent 
progression to overt DIC.
• Hepatic insufficiency may mimic DIC. 
Decreased production of clotting factors is 
common. Decreased clearance of normal 
fibrin(ogen)olytic by-products may increase 
FDP values. Mild idiopathic thrombocyto -
penia may also be seen. Spontaneous bleeding 
is uncommon unless DIC is present.
• Inflammatory leukogram, often with a 
stress component.
• Mild to moderate thrombocytopenia 
(40–100 × 103/μL); less reliable in cats.
• Anemia is possible. Red blood cell (RBC) 
fragmentation is a supportive finding.
• Biochemical changes reflect affected organs; 
acute kidney injury may result in 
isosthenuria, oligo-anuria, or the 
identification of casts in urine sediment.
• Prolonged clotting tests (PT, APTT); 
APTT is prolonged first, PT becomes 
prolonged with transition to overt DIC.
• Hypofibrinogenemia, although 
inflammatory increase may mask 
consumption.
• Increased FDPs and D-dimers. D-dimers 
are very sensitive and specific. DIC is unlikely 
if D-dimers are low/negative. Neither test is 
specific enough alone to diagnose DIC.
• Decreased AT; may be a positive acute 
phase reactant in cats, masking consum-  
ption.
• Thromboelastography may provide 
evidence of hypocoagulability or fibrinolysis.
Diagnostic procedures should be focused on 
identifying the inciting cause of inflamma-
tion, and may include imaging, tissue biopsy, 
or surgery as dictated by clinical signs.
• Usually related to the primary disease or 
DIC-affected organs.
• Petechiae common.
  TREATMENT
• Requires intensive inpatient treatment.
• Aggressive treatment of the primary disease 
is essential (e.g., antimicrobials for sepsis).

414  Blackwell’s Five-Minute Veterinary Consult  
DNURSING CARE
• Maintain tissue perfusion and oxygenation 
using fluids, transfusions, and oxygen therapy.
• Restore depleted factors by blood/plasma 
transfusions. Use fresh frozen plasma 
(10–20 mL/kg) to correct bleeding due to 
factor deficiency.
ACTIVITY
Limited by disease severity.
DIET
Maintain nutritional support as appropriate 
for the clinical condition of the patient.
Inform the owner that the condition is 
life-threatening with a guarded to poor 
Related to primary disease. Plasma or whole 
blood transfusion to restore clotting factors is 
a presurgical consideration. Surgery may be 
contraindicated with uncontrolled bleeding.
• There is no specific pharmacologic therapy 
for DIC per se.
• Heparin may be used in patients that have 
overt thrombosis or in those at high risk of 
thrombosis with normal coagulation times. 
Unfractionated heparin is preferred to low 
molecular weight heparin in human patients 
with DIC.
• Heparin binds to and potentiates the action 
of AT. Plasma or blood transfusions may be 
needed to replenish AT for heparin to be an 
effective anticoagulant.
• Starting doses for unfractionated heparin 
are 150–200 U/kg SC q8h. It may also be 
given as a CRI starting at 20–30 U/kg/h IV 
(i.e., same total daily dosage). Therapy should 
be monitored using serial measurements of 
APTT or anti-Xa activity.
• Heparin therapy should be avoided in 
patients with coagulopathy.• Inhibitors of fibrinolysis should not be used.
• The use of antiplatelet medications in 
thrombocytopenic patients is not indicated.
• Corticosteroids impair function of 
mononuclear phagocytes and do not have a 
clear indication for DIC unless important for 
therapy of the underlying disease (e.g., 
lymphoma).
• Heparin may cause hemorrhage, and 
therapy should be monitored.
• Volume overload may occur in cases with 
renal or pulmonary compromise.
None
  FOLLOW-UP
• Clinical improvement and the arrest of 
bleeding are key positive findings.
• Daily lab testing (e.g., coagulation tests, 
fibrinogen, platelet counts) is warranted in severe 
cases to identify positive or negative trends. Less 
frequent testing may suffice in milder cases.
• Coagulation times and fibrinogen often 
normalize more rapidly than FDPs and 
platelet counts.
Early detection of non-overt DIC can allow 
therapy before disease progresses to overt DIC.
Aside from the primary disease, affected 
organs may have permanent dysfunction or 
marginal reserve capacity.
For overt DIC, mortality rates for dogs range 
from 50% to 77%. For cats, rates may be >90%.
Unlike in humans, obstetric complications are 
not a common cause in dogs and cats.SYNONYMS
• Consumptive coagulopathy.
• Disseminated intravascular coagulopathy.
SEE ALSO
• Coagulation Factor Deficiency.
time.
• FDP = fibrin degradation product.
• PS = phosphatidylserine.
• TF = tissue factor.
Dunn ME. Acquired coagulopathies. In: 
Veterinary Internal Medicine: Diseases of 
the Dog and Cat, 7th ed. St. Louis, MO: 
Saunders, 2010, pp. 797–801.
O’Brien M. The reciprocal relationship 
between inflammation and coagulation. 
Top Companion Anim Med 2012, 
27:46–52.
Ralph AG, Brainard MB. Update on 
disseminated intravascular coagulation: 
when to consider it, when to expect it, 
when to treat it. Top Companion Anim 
Med 2012, 27:65–72.
Stokol T. Laboratory diagnosis of dissemi-
nated intravascular coagulation in dogs and 
cats: the past, the present, and the future. 
Vet Clin North Am Small Anim Pract 2012, 
42:189–202.
Author  John A. Christian
available onlineDisseminated Intravascular Coagulation  (continued)

Canine and Feline, Seventh Edition  415
D
Drowning (Near Drowning)
  BASICS
OVERVIEW
• Defined as process of experiencing 
respiratory impairment from submersion or 
immersion in liquid; near drowning defined as 
water submersion followed by survival for at 
least 24 hours; recent changes in terminology 
prefer the use of “death, morbidity or no 
morbidity following a drowning episode.” 
• Following submersion, elevations in CO2 
levels in the bloodstream stimulate respiration, 
and subsequent aspiration of water occurs. 
• Fresh water aspiration dilutes pulmonary 
surfactant, leading to alveolar collapse ± 
infectious pneumonia; hypertonic seawater 
aspiration leads to diffusion of interstitial water 
into alveoli; large volumes of water are not 
typically aspirated, but any amount results in 
ventilation–perfusion mismatch, hypoxemia, 
and metabolic acidosis. • Submersion time, 
temperature of water, and type of water (fresh 
vs. salt vs. chemical water) significantly affect 
development of organ damage.
Dogs and cats. Approximately half of animals 
involved in immersion accidents are <4 
SIGNS
• Noted acutely after exposure to water. 
• Cyanosis, apnea, respiratory distress. 
• Coughing ± clear to frothy red sputum. 
• Vomiting. • Obtunded to comatose. 
• Crackles or wheezes auscultated over chest. 
• Tachycardia or bradycardia, asystole.
• Greater risk near bodies of water (including 
pools, buckets, bathtubs) or ice. • Owner 
negligence or inadequate safety precautions 
vs. purposeful harm. • Animals in or near 
water at time of seizure, head trauma, 
hypoglycemic event, cardiac arrhythmia, or 
syncopal episode are at risk of drowning.
  DIAGNOSIS
• Hypothermia, neck trauma, and meningitis. 
• With drowning secondary to seizure, head 
trauma, hypoglycemic event, cardiac 
arrhythmia, or syncopal episode, history at 
time of presentation may be informative.
• Fresh water inhalation/ingestion—
hemodilution, hemolysis, and decreases in 
sodium, chloride, and urine specific gravity. 
• Hypertonic salt water ingestion/inhalation—hemoconcentration and increases in sodium, 
chloride, and urine specific gravity.
Arterial blood gas reveals hypoxemia (partial 
pressure of oxygen [PaO2] <80 mmHg), 
hypoventilation (partial pressure of carbon 
dioxide [PaCO2] >50 mmHg), and acid-base 
derangements.
IMAGING
• Radiographic changes may not be detectable 
for 24–48 hours. • Focal or diffuse alveolar 
pattern due to aspiration pneumonia or 
noncardiogenic pulmonary edema. • Mixed 
patterns may be present, ± radiopaque material 
filling the airways (“sand bronchogram”). 
• Foreign body inhalation may produce 
segmental atelectasis. • Progression of 
pulmonary injury to acute respiratory distress 
syndrome (ARDS) is possible and may appear as 
bilateral, diffuse, symmetric alveolar infiltrates.
• Endotracheal or transtracheal wash with 
cytologic evaluation and culture with 
sensitivity indicated if animal is stable. • ECG 
monitoring. • Cervical radiographs, CT or 
MRI of brain, and brainstem auditory evoked 
response (BAER) assessment in select cases.
  TREATMENT
• Initiate mouth-to-muzzle resuscitation 
on-site. • Emergency inpatient care is 
required. • Airway clearance, if obstructed, is 
first priority. • Cardiopulmonary resusci -
tation (CPR), if necessary. • Oxygen 
supplementation. • Intubation and mechanical 
ventilation with positive end-expiratory 
pressure may be required in animals with 
severe hypoxemia, hypercapnia, or imminent 
respiratory fatigue. • Fluid therapy and 
acid-base/electrolyte management are crucial. 
• Gradually rewarm (over 2–3 hours) 
hypothermic animals. • Gravitational 
drainage or abdominal thrusts (Heimlich 
maneuver) are not recommended in absence 
of airway obstruction owing to high risk of 
regurgitation and subsequent aspiration of 
stomach contents. • Continuous venovenous 
filtration may decrease mortality following 
salt water drowning.
• Mannitol 0.5 g/kg IV over 30 min may be 
beneficial in animals with suspected cerebral 
edema. • Broad-spectrum antibiotics (e.g., 
ampicillin 22 mg/kg IV q8h; enrofloxacin 10–20 mg/kg IV q24h in the dog, 5 mg/kg 
IV q24h in the cat) for aspiration pneumonia. 
• Beta-2 agonists may help animals with 
suspected bronchospasm. • Pentoxifylline 
decreased incidence of lung injury in dogs 
with experimental freshwater aspiration.
• Corticosteroid therapy not indicated; use 
could be detrimental in animals with aspiration 
pneumonia. • Use of enrofloxacin in young 
animals may result in cartilage erosion.
  FOLLOW-UP
• Continuous monitoring of heart rate and 
rhythm, respiratory rate, mucous membrane 
color and capillary refill time, urine output, 
arterial blood pressure, rectal temperature, and 
neurologic status. • Arterial blood gas, CBC, 
biochemical profile, coagulation profile, and 
acid-base status checked as needed.
Close monitoring of animals (especially 
young and old/debilitated animals) near 
bodies of water. Place barriers around bodies 
of water, life jackets on animals, train owners 
to perform CPR.
Aspiration pneumonia, noncardiogenic 
pulmonary edema, ARDS, gastrointestinal 
bleeding, diarrhea, vomiting, acute kidney 
injury, permanent neurologic derangements, 
disseminated intravascular coagulation, 
central diabetes insipidus.
Directly related to animal’s status at time of 
admission—animals that present comatose, 
severely acidotic (pH <7.0), or requiring 
cardiopulmonary resuscitation or mechanical 
ventilation have poor prognosis. Animals that 
present conscious have good prognosis if no 
complications ensue; 37.5% mortality rate in 
15 dogs and 1 cat with freshwater aspiration.
response. • CPR = cardiopulmonary 
resuscitation. • PaCO2 = partial pressure of 
carbon dioxide. • PaO2 partial pressure of 
oxygen.
Author  Deborah C. Silverstein

416  Blackwell’s Five-Minute Veterinary Consult  
DDuctal Plate Malformation (Congenital Hepatic Fibrosis)
  BASICS
• Ductal plate malformations (DPMs) are 
congenital noninflammatory hepatopathies 
subject to complicating bacterial cholangitis; 
recognized most often in juvenile and young 
adult dogs or cats and reflect malformation of 
biliary structures. •  DPMs reflect aberrant 
development, differentiation, proliferation, or 
intussusceptive resorption of embryonic 
anlage of bile ducts during development of 
ductal plate, embryologic precursor of portal 
tract structures (predominantly bile ducts). 
• Pathomechanisms leading to DPM 
interfere with tubulogenesis—may affect 
kidneys, liver, or pancreatic ductal structures. 
• Four DPM phenotypes defined based on 
involved structures and severity of coexistent 
portal tract fibrosis, severity of fibroductal 
bridging trabeculae, development of 
presinusoidal portal hypertension (PH) 
causing splanchnic hypertension, and 
development of acquired portosystemic 
shunts (APSS). •  Animals with DPM have 
propensity for septic suppurative cholangitis, 
choledochitis, cholelithiasis, or extrahepatic 
bile duct obstruction (EHBDO).
MAJOR DPM PHENOTYPES
• Choledochal cyst —diverticulum protruding 
from common bile duct (CBD) or cystic duct; 
propensity for infection similar to appendicitis 
in humans; may cause systemic sepsis, EHBDO, 
and cranial abdominal mass effect; complex 
confusing US appearance. •  Caroli’s 
malformation —irregular duct silhouettes 
(sacculation, invagination, or “budding” 
protrusions) with occasional periductal 
satellite ductal elements surrounding large 
ducts; malformations variably involve hepatic, 
interlobular, or large intralobular bile ducts; 
biliary epithelium may appear normal, 
hyperplastic, attenuated, or vacuolated; 
intraluminal debris in large ducts; develop 
choleliths, dystrophic mineralization, septic 
cholangitis. • Small proliferative-like 
phenotype —diffuse intralobular bile duct 
malformation without or with bridging 
portal-to-portal fibroductular trabeculae: if 
fibrosis severe may evolve presinusoidal PH 
and consequent splanchnic hypertension = 
congenital hepatic fibrosis (CHF) phenotype —
involves small intralobular bile duct malfor -
mation with densely packed proliferative-like 
ductule structures (± luminal apertures) within 
excessive extracellular matrix (ECM); ECM 
accrual varies in severity, but appears 
progressive with aging; histologic features 
characterized by amalgamation of proliferative 
bile ductules with numerous stout (muscular) 
entangling arterials and inconspicuous portal 
veins within exuberant ECM that 
dimensionally expands portal tracts; variable fibroductal bridging partitions may 
interconnect portal regions; because ECM 
accrues with aging, transformation to CHF 
may occur over time. •  von Meyenburg’s 
complexes (VMCs) —isolated single microscopic 
DPM composed of clustered proliferative 
intralobular bile duct profiles embedded in 
expanded ECM; also termed bile duct 
hamartomas; usually located adjacent to liver 
capsule; inconsequential malformation. 
• Progression of portal tract fibrosis with 
aging can lead to gradual onset of presinusoidal 
PH, formation of APSS, ascites, and hepatic 
encephalopathy (HE). • Gallbladder (GB) 
agenesis and severe hypo  plasia or agenesis of 
entire liver lobes may occur. •  Liver lobes may 
be variably affected with DPM; unaffected 
liver lobes possible.
• DPMs not associated with increased liver 
enzymes or jaundice unless complicated by 
infection, choleliths, EHBDO, or choledochitis. 
• Different phenotypes acquire different 
disease manifestations. •  Choledochal 
cysts— not recognized until cystic luminal 
contents contaminated by bacteria with 
ensuing infection and cyst expansion, 
development of choledochitis or EHBDO; 
until compromised CBD patency patient 
remains anicteric, usually asymptomatic. 
• Caroli’s malformation— serendipitously 
recognized on abdominal radiography (limy 
gallbladder, mineralized sacculated 
intrahepatic large bile ducts), or on 
abdominal US as distended intra- or 
extrahepatic bile ducts, mineralized ducts, 
association with cholelithiasis, or thickened 
duct walls (infection, choledochitis). 
• Diffuse DPM without extensive bridging 
fibrosis or presinusoidal PH —not associated 
with increased liver enzymes or jaundice, 
usually normal total serum bile acid (TSBA) 
concentrations; diagnosed when infection 
increases liver enzyme activity leading to liver 
biopsy. •  Diffuse DPM with bridging fibrosis 
(CHF) causes presinusoidal PH —these patients 
may present for ascites, increased TSBA 
concentrations, ± increased liver enzymes 
reflecting secondary cholangitis, or for HE; 
not jaundiced unless infected or have 
concurrent EHBDO.
• Liver—variable size (small, normal, large); 
may have GB agenesis or maldevelopment of 
entire liver lobe(s); rare concurrent congenital 
intrahepatic or extrahepatic congenital 
portosystemic vascular anomaly (shunt, 
PSVA); jaundice due to EHBDO from 
choledochal cyst, cholelithiasis, rare cholangio  - 
carcinoma, or due to sepsis (Caroli’s 
malformation, choledochal cyst); increased 
liver enzymes may reflect suppurative 
cholangitis or unrelated copper associated 
hepatopathy (CuAH) in dogs. • Gastrointestinal (GI)—anorexia; 
intermittent vomiting or diarrhea reflects 
concurrent inflammatory bowel disease (IBD) 
or enteric hypertensive vasculopathy (splanchnic 
hypertension from presinusoidal PH). 
• Nervous—episodic HE if APSS associated 
with CHF or if concurrent PSVA. 
• Musculoskeletal—stunted growth and poor 
body condition if CHF and APSS or if 
concurrent PSVA; also may reflect chronic 
disease, inappetence, or enteric malassimilation. 
• Urogenital—polyuria and polydipsia (PU/
PD); possible polycystic renal phenotype; 
ammonium biurate urolithiasis reflects APSS 
or rare concurrent PSVA. •  Hemic/lymphatic/  
immune—red blood cell (RBC) microcytosis 
reflects APSS or PSVA; neutrophilic 
leukocytosis with toxic neutrophils and 
left-shifted leukon reflects sepsis due to 
suppurative bacterial cholangitis/choledochitis 
or infected choledochal cyst.
• Dog and cat, no sex predilection. •  Juvenile 
and young adults predominate; dogs: mean 
age 1.5–2.5 years (0.2–12) years. •  May 
affect multiple littermates. •  Boxer dogs may 
be predisposed. •  Persian cats and descendent 
breeds with or without polycystic renal disease 
appear predisposed.
SIGNS
• May be asymptomatic. •  Stunted growth, 
poor body condition if CHF with APSS or 
concurrent PSVA. •  GI signs—inappetence, 
emesis, diarrhea, enteric hemorrhage; 
especially if concurrent IBD. •  PU/PD if 
APSS or rare concurrent PSVA, or polycystic 
renal disease. •  ± Increased liver enzymes.  
• ± Fever, leukocytosis, hyperbilirubinemia—
due to sepsis evolved from bacterial cholangitis, 
choledochitis, or choledochal cyst infection or 
infection-related cholelithiasis. •  ± Abdominal 
distention—ascites with APSS in CHF; CHF 
with PSVA no ascites unless PSVA attenuated. 
• ± Episodic CNS signs due to HE if APSS in 
CHF or rare concurrent PSVA. •  ± Urolithiasis 
(ammonium urates) if APSS in CHF or rare 
concurrent PSVA.
• In humans (and knockout mouse models)

SIGNS
• In humans (and knockout mouse models) 
DPM reflects gene mutations influencing 
structure or function of primary cilia; 
polycystic kidney disease in Persian cats 
involves polycystin-1 precursor gene, one 
gene influencing primary ciliary function; 
~15% develop hepatic DPM. •  Clinical signs 
usually reflect acquired complications.
  DIAGNOSIS
• Stunted growth, increased TSBA 
concentrations—PSVA, severe portal vein

Canine and Feline, Seventh Edition  417
Datresia, splanchnic portal vein thrombo -
embolism (TE). •  Increased liver enzymes ± 
hyperbilirubinemia—chronic hepatitis, 
CuAH, hepatotoxicity, liver abscess, primary 
hepatic neoplasia, cholangiohepatitis, 
choledochitis, or cholecystitis. •  Jaundice—
acute liver injury, hepatotoxicosis, chronic 
hepatitis, CuAH, cholelithiasis, ruptured GB, 
EHBDO, hemolysis. •  CNS signs—
infectious disorders (distemper); toxicities 
(lead); hydrocephalus; epilepsy; metabolic 
disorders (severe hypoglycemia, hypokalemia, 
hyperkalemia, hypophosphatemia); thiamine 
deficiency. •  Ascites—pure transudate, many 
causes (see Hypertension, Portal). •  HE—
APSS, PSVA, portal TE, other causes.
• CBC—RBC microcytosis: reflects APSS; 
target cells associated in dogs. 
• Biochemistry—if APSS with CHF: ± low 
albumin, cholesterol, blood urea nitrogen, 
variable globulin; all DPM phenotypes: ± 
increased alkaline phosphatase and alanine 
aminotransferase activity with cholangitis; 
hyperbilirubinemia: if EHBDO due to 
choledochal cyst or cholelithiasis or if septic. 
• Urinalysis—ammonium biurate crystalluria 
if APSS in CHF phenotype.
• Routine coagulation tests—variable 
abnormalities (see Coagulopathy of Liver 
Disease); low protein C and antithrombin 
activity may reflect APSS in CHF phenotype. 
• TSBA—increased concentrations in 
anicteric patients reflect APSS or rare 
concurrent PSVA. •  Peritoneal fluid 
analysis—pure transudate (protein <2.5 g/
dL); modified transudate if chronic: only in 
CHF phenotype.
IMAGING
• Abdominal radiography—variable liver size. 
• Abdominal effusion—APSS in CHF 
phenotype. •  Ammonium biurate calculi—
radiolucent unless radiodense mineral shell. 
• Thoracic radiography—normal.
Abdominal US
• Variable liver size—small to large. •  GB 
may not be discovered if atretic or may be 
tiny. •  May disclose intra- or extrahepatic 
biliary malformations (sacculated or cystic 
ductal structures); variable liver texture; 
unremarkable vasculature to portal hypo -
perfusion. •  Choledochal cyst—may be 
difficult to decipher owing to overlying 
enteric gas and confusion with CBD and 
cystic duct. •  Abdominal effusion—if APSS 
in CHF . •  APSS—confirm using color-flow 
Doppler; rule out portal TE and intrahepatic 
arteriovenous malformations as causes of 
APSS. •  Uroliths—renal pelvis or urinary 
bladder.Additional Imaging
• Colorectal or splenoportal scintigraphy with 
Technetium-99m pertechnetate (see Portosystemic 
Vascular Anomaly, Congenital)—sensitive 
noninvasive test confirming macroscopic 
shunting, but cannot differentiate PSVA from 
APSS. •  Multisector CT —gold standard 
imaging modality: confirms APSS or PSVA; 
dual-phase angiogram can reveal asymmetric 
liver development (liver lobe absence or atresia), 
GB atresia, choledochal cyst, sacculated 
interlobular and cystic ducts, cholelithiasis, 
and APSS.
• Fine-needle aspiration cytology—cannot 
diagnose DPM, sometimes identifies 
complicating bacterial infection especially if 
bile collected. •  Liver biopsy—mandatory for 
definitive diagnosis; open surgical wedge, 
laparoscopic cup samples; needle core sample 
may be adequate; collect biopsies from several 
liver lobes. •  Echocardiography—if ascites 
present.
• Gross—depends on phenotype. 
◦ Choledochal cyst— predominantly occurs in 
cats, variable size (as large as 10 cm) with thick 
or thin wall; contents acholic or mucinous white 
bile; may be purulent or bile laden; may envelop 
CBD. ◦ Caroli’s malformation —grossly 
distended hepatic, interlobular, or segmental 
bile ducts, thick walls if choledochitis, wall may 
be mineralized, may have pigmented-calcium 
carbonate choleliths. ◦ Small-proliferative-type 
DPM —firm fibrotic hepatic parenchyma, fine 
nodular to smooth capsular surface, may have 
splanchnic APSS if CHF phenotype. ◦ von 
Meyenburg complexes —inapparent or tiny pale 
foci on liver margin. •  Possible GB atresia, 
PSVA, other vascular malformations, liver lobe 
agenesis. •  Microscopic—variable severity as 
described (see Major DPM Phenotypes); 
stereotypic histologic features of portal venous 
hypoperfusion are common; direct intersection 
of proliferative-like bile ductules and hepatocytes 
is signature histologic feature of DPM in 
absence of inflammatory infiltrates; islands of 
hepatocytes may be encircled or isolated by 
portal-to-portal fibroductal partitions.
  TREATMENT
• Inpatient—for septic complications or 
severe HE. •  Surgical intervention—
choledochal cyst: best managed by resection 
but depends on anatomic malformation and 
location; may be marsupialized or anastomosed 
to intestine. •  Outpatient—stable patients. 
• Avoid endoparasitism. •  T reat infections 
promptly—DPM patients (except VMC) predisposed to bacterial cholangitis, 
choledochitis, and associated cholelithiasis 
because of blind-ended noncontiguous ductal 
structures; in CHF with APSS reduced 
Kupffer cell surveillance increases risk for 
infection and systemic sepsis. •  In CHF—
remain vigilant for ammonium biurate 
obstructive uropathy. •  If APSS—avoid 
nonsteroidal anti-inflammatories that may 
augment ascites and GI bleeding provoking 
HE; adjust dosage of drugs with high first-pass 
hepatic extraction. •  CuAH diagnosed by 
liver biopsy should be treated.
• HE—eliminate causal factors; individualize 
diet, supplement water-soluble vitamins, vitamin 
E, and K depending on prothrombin/activated 
partial thromboplastin time tests or presence of 
EHBDO; provide multiple small feedings daily. 
• Ascites—see Hypertension, Portal.
Strategy for DPM is to treat syndrome 
HE
• Lactulose (0.5–1.0 mL/kg PO q8–12h)—
achieve several soft stools daily; may withdraw 
with optimal diet modification. •  Oral 
antibiotics—modify encephalogenic enteric 
toxin production: first choices metronidazole 
(7.5 mg/kg PO q12h) or amoxicillin (22 mg/
kg PO q12h); avoid neomycin (20 mg/kg PO 
q8–12h): potential for enteric absorption 
(esp. if concurrent IBD) causing ototoxicity 
(deafness) and nephrotoxicity.
Ascites
• Dietary sodium restriction. •  Diuretics—
furosemide (1–4 mg/kg PO/IM/IV q12–24h): 
potassium wasting effect modulated by 
combination with spironolactone (1–4 mg/kg 
PO q12h, loading dose then maintenance 
dose 2–4 mg/kg PO q24h); potassium 
sparing; less potent than furosemide. 
• Diuretic-resistant ascites—consider 
therapeutic abdominocentesis (see Hypertension, 
Portal for other medical options). •  Antifibrotic—  
not proven effective in humans with DPM; 
liver transplant common, unknown in 
veterinary medicine; colchicine not effective. 
• Telmisartan—angiotensin receptor blocker 
safe for use in dogs and cats; attenuated 
progressive ECM accrual in DPM rodent 
model; adverse effects if coadministered with 
spironolactone or angiotensin-converting 
enzyme (ACE) inhibitor: leads to serious 
hypotension (collapse, acute renal failure); 
initial dose 0.5 mg/kg/day titrated to max of 
1 mg/kg/day.(continued)  Ductal Plate Malformation (Congenital Hepatic Fibrosis)

418  Blackwell’s Five-Minute Veterinary Consult  
DAntioxidant Medications
Indicated if chronic cholangitis, CuAH, 
chronic increased liver enzymes, or CHF .
Rare in CHF; may encounter if chronic 
EHBDO caused by choledochal cyst or 
GI Hemorrhage
Hypertensive enteric vasculopathy may be 
encountered with CHF because of APSS.
• Avoid or reduce dosage of drugs relying on 
first-pass hepatic metabolism if APSS; avoid 
drugs reacting with GABA-benzodiazepine 
receptors if intermittent HE in patients with 
APSS-CHF phenotype; avoid drugs inhibiting 
biotransformation and metabolism of other 
drugs (e.g., cimetidine, chloramphenicol, 
quinidine, some calcium channel blockers); if 
jaundiced avoid drugs undergoing biliary 
elimination. •  Avoid metoclopramide if 
spironolactone used as diuretic (augments 
aldosterone). •  Avoid combination of 
spironolactone with telmisartan or ACE 
  FOLLOW-UP
• Instruct owners to monitor body 
temperature, appetite, activity, for jaundice 
or other signs of infection or complications. • Biochemistry—initially monitor q2–4 
weeks until stabile in animals presenting 
with sepsis or EHBDO, then q4–6 months 
or if cyclically ill or febrile; monitor for 
recurrent septic cholangitis/choledochitis, 
development of septic effusion; HE 
decompensation.
CHF associated with HE—requires indefinite 
nutritional and medical management. If 
concurrent PSVA—likely cannot be 
attenuated without causing APSS.
• Long-term survival (years) possible. 
• Guarded prognosis if CHF phenotype with 
APSS. •  Short-term or lifelong treatments 
may be required. •  Flare-ups of HE and 
ascites may require hospitalizations for 
adjustment of nutritional and medical 
interventions.
• HE. •  Ascites. •  GI bleeding. •  APSS.
• Prognosis depends on degree of fibrosis and 
APSS in CHF; severity of relapsing septic 
cholangitis or choledochal cyst infection; 
intrahepatic infected cholelithiasis; evidence 
of hepatic insufficiency and APSS at initial 
diagnosis. •  Fibrosis progressive with aging in 
some patients.SEE ALSO
• Ascites.
• APSS = acquired portosystemic shunts.
• CHF = congenital hepatic fibrosis.
• ECM = extracellular matrix.
• EHBDO = extrahepatic bile duct occlusion.
• PH = portal hypertension.
• PSVA = portosystemic vascular anomaly. 
• TE = thromboembolism.
• VMC = von Meyenburg’s complex.
Brown DL, Van Winkle T, Cecere T, et al. 
Congenital hepatic fibrosis in 5 dogs. Vet 
Pathol 2010, 47:102–107.
Pillai S, Center SA, McDonough SP , et al. 
Ductal plate malformation in the liver of 
boxer dogs: clinical and histological 
features. Vet Pathol 2016, 53:602–613.
Consulting Editor  Kate HolanDuctal Plate Malformation (Congenital Hepatic Fibrosis)  (continued)

Canine and Feline, Seventh Edition  419
D
Dysautonomia (Key-Gaskell Syndrome)
  BASICS
OVERVIEW
• Failure of autonomic function in multiple 
organs with minimal motor or sensory 
involvement. •  Young adult, rural dogs in 
specific states at greatest risk. •  T reatment 
is symptomatic and prognosis guarded.
• Dog and less commonly cat. •  No breed or 
sex predilection. •  Median age is 18 months 
but any age animal may be affected.
SIGNS
• Acute to subacute onset (5–14 days). 
• Various combinations of signs may be 
present, but both sympathetic and para­
sympathetic signs in various organs are 
necessary to be confident of diagnosis. 
• Sensory or motor deficits are minimal.
Presenting Complaints
• Most commonly gastrointestinal (GI) signs 
of vomiting or regurgitation, diarrhea, or 
occasionally constipation. •  Straining to 
urinate and dribbling urine. •  Photophobia 
and third ­eyelid elevation. •  Dyspnea, 
coughing, and purulent nasal discharge. 
• Depression, anorexia, and weight loss.
Examination Findings
• Variable combinations of autonomic 
dysfunction. •  Loss of anal sphincter tone. 
• Dry nose and mucous membranes; lack of 
tear production. •  Distended, easily expressed 
bladder. •  Pupils midrange to maximally 
dilated with no pupillary light reflex but 
intact vision. •  Third ­eyelid elevation, ptosis, 
and enophthalmos. •  Lack of gut sounds and 
occasional abdominal pain. •  Heart rate and 
blood pressure typically in low end of normal 
range but do not rise in response to stress. 
• Secondary aspiration pneumonia or 
rhinitis. •  Cachexia. •  Occasionally mild 
proprioceptive deficits or weakness.
• Cause unknown. •  Highest incidence in 
Missouri, Oklahoma, and Kansas as well as 
Wyoming and northern Colorado, but occasional 
cases reported throughout United States. 
• Free­roaming, rural dogs at greatest risk.
  DIAGNOSIS
• Anticholinergic toxicity. •  Other 
differential diagnoses depend upon specific 
clinical signs: e.g., urinary tract infection for 
dysuria, corneal ulcer for photophobia, 
dehydration for dry mucous membranes.
UnremarkableIMAGING
• Megaesophagus ± aspiration pneumonia. 
• Distended bowel loops with no peristalsis. 
• Distended urinary bladder. 
• Echocardiography may show systolic 
dysfunction as reduced fractional short  ­ 
ening.
• If pupils affected, 0.05% pilocarpine drops 
in one eye will produce miosis within 60 
minutes; rules out anticholinergic toxicity. 
• Atropine (0.03 mg/kg IV) may not produce 
expected rise in heart rate; suggests loss of 
vagal tone. •  Intradermal histamine may 
produce no response or wheal but no flare; 
demonstrates loss of sympathetic innervation 
of arterioles.
  TREATMENT
• IV fluids to prevent dehydration. •  High ­
calorie food; feeding tube to ensure adequate 
nutrition if megaesophagus present; if GI 
motility absent, parenteral nutrition may be 
necessary. •  Lubricating eye drops if tear 
production insufficient. •  Humidification of 
air may help with dry mucous membranes. 
• Manual bladder expression.
• Antibiotics as needed to treat secondary 
infections. •  Prokinetic drug such as 
metoclopramide if GI motility affected. 
• Bethanechol to stimulate lacrimation and 
urination (start at 0.05 mg/kg q8–12h and 
adjust dose based on response); manual 
expression of bladder more reliable. 
• Ocular pilocarpine to relieve photophobia. 
• Pimobendan if poor cardiac contractility.
• Animals with dysautonomia develop 
denervation supersensitivity to direct acting 
cholinergic or adrenergic drugs. •  Great care 
must be exercised in using such drugs, 
particularly adrenergic drugs that could 
precipitate fatal tachyarrhythmias; best to 
start at <10% of low end of dose range when 
using direct ­acting drugs and escalate dose as 
needed to produce desired effect.
  FOLLOW-UP
• Prognosis guarded; most animals die of 
aspiration pneumonia or euthanasia due to 
poor quality of life. •  Animals who survive 
often have some degree of permanent autonomic dysfunction that may require 
constant care.
• Necropsy identification of neuronal loss in 
ganglia confirms diagnosis. •  Clinical 
diagnosis based on autonomic failure in 
multiple organs without underlying cause or 
significant motor or sensory involvement and 
appropriate response to pharmacologic testing.
Berghaus RD, O’Brien DP , Johnson GC, 
Thorne JG. Risk factors for development of 
dysautonomia in dogs. J Am Vet Med Assoc 
2001, 218:1285–1292.
Harkin KR, Andrews GA, Nietfeld JC. 
Dysautonomia in dogs: 65 cases (1993–
2000). J Am Vet Med Assoc 2002, 
220:633–644.
Harkin KR, Bulmer BJ, Biller DS. 
Echocardiographic evaluation of dogs with 
dysautonomia. J Am Vet Med Assoc 2009, 
235:1431–1436.
Kidder AC, Johannes C, O’Brien DP , et al. 
Feline dysautonomia in the Midwestern 
United States: a retrospective study of nine 
cases. J Fel Med Surg 2008, 10:130–136.
Longshore RC, O’Brien DP , Johnson GC, 
et al. Dysautonomia in dogs—a retrospective 
study. J Vet Intern Med 1996, 
10(3):103–109.
O’Brien DP , Johnson GC. Dysautonomia 
and autonomic neuropathies. Vet Clin 
North Am Small Anim Pract 2002, 
32:251–265.
Author  Dennis P . O’Brien

420  Blackwell’s Five-Minute Veterinary Consult  
DDyschezia and Hematochezia
  BASICS
• Dyschezia—painful or difficult defecation.
• Hematochezia—bright red blood in or on 
the feces.
Results from inflammatory, infectious, or 
neoplastic conditions affecting the colon, 
rectum, or anus.
• No breed or sex predilection.
SIGNS
• Vocalizing and whimpering during 
defecation.
• Tenesmus.
• Decreased frequency of defecation in 
association with severe dyschezia (animal 
resists defecating due to pain), resulting in 
constipation or obstipation.
• Mucoid, bloody diarrhea with a marked 
increase in frequency and scant fecal volume 
in patients with colitis.
• Scooting behavior in association with anal 
gland infection or impaction.
• It is pivotal to differentiate hematochezia 
secondary to colitis from hematochezia 
secondary to a colorectal mass—the histories are 
profoundly different and a rectal examination 
should always be performed to further 
differentiate these two disorders (see below).
• Rectal examination may reveal hard feces 
(constipation or obstipation), diarrhea 
(colorectal disease), colorectal masses, 
anorectal thickening, rectal or colonic 
strictures, anal sac enlargement/pain, 
prostatomegaly, or perineal hernias.
• Fistulous tracts around anus occur with 
perianal fistulae.
• Anal occlusion with matted hair and feces 
occurs with pseudocoprostasis.
CAUSES
Rectal/Anal Disease
• Stricture or spasm.
• Anal sacculitis or abscess.
• Perianal fistulae.
• Rectal or anal foreign body.
• Pseudocoprostasis.
• Rectal prolapse.
• T rauma—bite wounds, etc.
• Neoplasia—adenocarcinoma, lymphoma, 
and anal sac tumors.
• Rectal polyps.
• Mucocutaneous lupus erythematosus.Colonic Disease
other tumors.
• Idiopathic megacolon—cats.
• Inflammation—inflammatory bowel 
disease, infectious parasitic agents, colitis 
secondary to dietary-responsive enteropathy 
(see Colitis and Proctitis).
• Constipation (see Constipation and 
Obstipation).
Extraintestinal Disease
• Fractured pelvis or pelvic limb.
• Prostatic disease.
• Perineal hernia.
• Intrapelvic neoplasia.
• Ingestion of hair, bone, or foreign material 
may contribute to constipation and subse -
quent dyschezia.
• Environmental factors such as a dirty litter 
pan or infrequent outside walks may contribute 
to constipation and subsequent dyschezia.
  DIAGNOSIS
It is pivotal to recognize that hematochezia in 
animals can be seen with both diffuse colitis 
as well as with focal or discrete colorectal 
neoplasms. The fundamental differences in 
the clinical presentation between the two 
disorders can usually be recognized during the 
history and following a thorough physical 
examination, including a rectal examination. 
Dogs with colorectal neoplasms do not have 
diarrhea, and the most important and 
frequent clinical sign is hematochezia in the 
absence of an increase in defecation frequency 
or change in stool consistency. Pencil-thin or 
ribbon-like stools can be seen when the 
colorectal neoplasm is advanced, causing a 
change in the shape of the stool. A rectal 
examination must be performed on every patient 
with a history of hematochezia or dyschezia .
• Dysuria, stranguria, or hematuria—
abnormal findings on urinalysis, such as 
pyuria, crystalluria, or bacteriuria. The history 
and physical examination should differentiate 
whether the animal is having difficulty 
urinating or defecating.
• Dystocia—differentiate with history and 
imaging.
• Usually unremarkable, unless there is a 
history of chronic blood loss with secondary 
iron deficiency causing a microcytic and 
hypochromic nonregenerative anemia.
• Mild neutrophilia (with or without a left 
shift) with infection or inflammation.
Centrifugation fecal flotation to help rule 
out parasitic causes of colitis.IMAGING
• Pelvic radiographs may reveal intrapelvic 
disease, foreign body, or fracture.
• Ultrasonography may demonstrate prostatic 
disease or caudal abdominal masses; however, 
a portion of the descending colon cannot be 
visualized because of the pelvis.
Colonoscopy/proctoscopy to evaluate for 
inflammatory or neoplastic disease.
  TREATMENT
• Depends on the underlying cause.
• Colonic strictures secondary to neoplasms 
can be managed via surgical excision or 
balloon catheter dilation.
• Consider laxatives (lactulose) to ease 
defecation and discomfort in animals with 
colorectal strictures or masses.
• Colorectal masses are best removed 
surgically or via endoscopy (snare and 
cauterization for polyps).
• Antibiotics—if bacterial infection (e.g., 
anal sac abscess); amoxicillin/clavulanic acid 
15 mg/kg PO q12h for 7–10 days.
• Anti-inflammatory drugs—sulfasalazine or 
prednisone (dogs) and prednisolone (cats) if 
colitis is present (see Colitis and Proctitis; 
Colitis, Histiocytic Ulcerative).
• Cyclosporine (5 mg/kg q12h for 3–4 
months with gradual taper thereafter) for 
dogs with perianal fistulae.
• Laxatives—lactulose 1 mL/4.5 kg PO 
q8–12h to effect; docusate sodium or 
docusate calcium: dogs: 50–100 mg PO 
q12–24h; cats: 50 mg PO q12–24h.
• Cisapride—prokinetic indicated for cats 
with moderate to severe megacolon (and no 
evidence of obstruction) in conjunction with 
lactulose and dietary therapy at a dose of 
5 mg/cat q12h.
Avoid agents that cause increased fecal bulk 
(insoluble fiber), unless specifically indicated 
(colitis).
  FOLLOW-UP
• The need for follow-up depends on the 
underlying cause. Dogs and cats that are 
undergoing balloon dilation of colorectal 
strictures usually require multiple procedures 
to manage the stricture properly. Animals 
should always be rechecked at suture removal

Canine and Feline, Seventh Edition  421
D
or 10–14 days following surgical resection of 
colorectal masses.
• Animals with hematochezia secondary to 
colitis should have a marked improvement or 
resolution of their clinical signs within 5–7 
days following implementation of elimination 
dietary therapy.
Daily monitoring by the owner with periodic 
phone calls to the clinician every 2–3 weeks 
during the beginning of treatment.
• May see fecal incontinence following 
surgical resection of anal sacs or colorectal 
tumors if anal sphincter is compromised.• Secondary megacolon may occur if 
obstipation is severe and long term.
N/A
Caution with corticosteroids, antibiotics.
SEE ALSO
• Constipation and Obstipation. Suggested Reading
Adamovich-Rippe KN, Mayhew PD, Marks 
SL, et al. Colonoscopic and histologic 
features of rectal masses in dogs: 82 cases 
(1995–2012). J Am Vet Med Assoc 2017, 
250(4):424–430.
Webb CB. Anal-rectal disease. In: Bonagura 
JD, T wedt DC, eds., Current Veterinary 
Therapy XIV. St. Louis, MO: Elsevier, 
2009, pp. 527–531.
Zoran DL. Rectoanal disease. In: Ettinger SJ, 
Internal Medicine, 6th ed. St. Louis, MO: 
Elsevier, 2005, pp. 1408–1420.
Consulting Editor  Mark P . Rondeau(continued)  Dyschezia and Hematochezia

422  Blackwell’s Five-Minute Veterinary Consult  
DDysphagia
  BASICS
• Dysphagia refers to difficulty in swallowing 
and is far more commonly seen in dogs than 
cats.
• Dysphagia is divided into three main 
categories—oropharyngeal, esophageal, and 
gastroesophageal causes.
• Oropharyngeal causes of dysphagia can be 
further subcategorized into oral, pharyngeal, 
or cricopharyngeal.
• Any disorder causing difficulty with 
prehension or mastication can cause 
dysphagia.
• Odynophagia refers to painful swallowing 
and is most commonly seen in association 
with pharyngitis, pharyngeal foreign bodies, 
esophageal foreign bodies, or severe 
esophagitis.
• Esophageal dysphagia is discussed in 
Megaesophagus and in Regurgitation.
• The oral preparatory phase  is voluntary and 
begins as food or liquid enters the mouth. 
Mastication and lubrication of food are the 
hallmarks of this phase. Abnormalities of the 
oral preparatory phase usually are associated 
with dental disease, xerostomia, weakness of 
the lips (cranial nerves [CN] V and VII), 
tongue (CN XII), and cheeks (CN V and 
VII).
• The oral phase  of swallowing consists of the 
muscular events responsible for movement of 
the bolus from the tongue to the pharynx and 
is facilitated by tongue, jaw, and hyoid muscle 
• The pharyngeal phase  begins as the bolus 
reaches the tonsils and is characterized by 
elevation of the soft palate to prevent the 
bolus from entering the nasopharynx, 
elevation and forward movement of the 
larynx and hyoid, retroflexion of the epiglottis 
and closure of the vocal folds to close the 
entrance into the larynx, contraction of the 
muscles of the pharynx, and relaxation of the 
cricopharyngeus muscle that makes up much 
of the proximal esophageal sphincter (PES) to 
allow passage of the bolus into the esophagus. 
Respiration is briefly halted (apneic moment) 
during the pharyngeal phase.
• Abnormalities of the pharyngeal phase of 
swallowing are associated with pharyngeal 
weakness secondary to neuropathies or 
myopathies, pharyngeal tumors or foreign 
bodies, or cricopharyngeus muscle disorders.
• The esophageal phase  is involuntary and 
begins with relaxation of the PES and 
movement of the bolus into the esophagus.
• Nervous.• Neuromuscular.
GENETICS
Breeds that have a hereditary predisposition or 
high incidence of dysphagia include golden 
retriever (pharyngeal weakness, 
cricopharyngeal muscle dysfunction), cocker 
and springer spaniels (cricopharyngeal muscle 
dysfunction), Bouvier des Flandres and cavalier 
King Charles spaniel (muscular dystrophy), 
and boxer (inflammatory myopathy). In 
addition, large and giant-breed dogs are 
predisposed to acquired megaesophagus.
Variable depending on underlying etiology. 
Megaesophagus one of the most common 
causes of dysphagia in dogs.
None
• Congenital disorders that cause dysphagia 
(e.g., cricopharyngeal muscle achalasia, cleft 
palate, hiatal hernia) usually diagnosed in 
animals <1 year old.
• Acquired esophageal dysmotility and 
pharyngeal weakness more common in older 
patients.
SIGNS
• Drooling (due to pain or inability to swallow 
saliva), gagging, ravenous appetite, repeated or 
exaggerated attempts at swallowing, swallowing 
with head in abnormal position, nasal 
discharge (due to nasal reflux of food and 
liquids into nasopharynx), coughing (due to 
aspiration), regurgitation, painful swallowing, 
and occasionally anorexia and weight loss. If 
tongue is not functioning normally, problems 
with prehension and mastication may be seen.
• Ascertain onset and progression. Foreign 
bodies cause acute dysphagia; pharyngeal 
dysphagia may be chronic and insidious in 
onset.
• Physical examination must include careful 
examination of oropharynx using sedation or 
anesthesia if necessary to help rule out morph  - 
ologic abnormalities such as dental disease, 
foreign bodies, cleft palate, glossal abnormalities, 
and oropharyngeal tumors.
• Evaluation of cranial nerves should be 
performed, including assessment of tongue 
and jaw tone, and of laryngeal function.
• Complete physical and neurologic exam  - 
ination may identify clinical signs supporting 
generalized neuromuscular disorder, including 
muscle atrophy, stiffness, or decreased or 
absent spinal reflexes.
• Evaluate gag reflex by placing a finger in the 
pharynx; however, presence or absence of gag 
reflex does not correlate with efficacy of pharyngeal swallow nor adequacy of 
deglutitive airway protection.
• The importance of the clinician’s carefully 
observing the dysphagic animal while eating 
(kibble and canned food) and drinking in 
hospital (or at home via video) is pivotal, and 
such observation helps localize the problem to 
oral cavity, pharynx, or esophagus.
Oral Dysp  hagia
• Modified eating behavior (e.g., eating with 
head tilted to one side or having difficulty 
prehending the bolus or opening the mouth).
• Tongue paralysis or dystrophy, dental 
disease, masticatory muscle myositis, 
temporal muscle atrophy, or pain, and food 
packed in buccal folds suggest oral dysphagia.
Pharyngeal Dysphagia
• Prehension of food is normal.
• Repeated attempts at swallowing with food 
falling out of mouth and excessive gagging 
suggest pharyngeal dysphagia.
• Saliva-coated food retained in buccal folds, 
diminished gag reflex, and nasal discharge 
may also exist.
Cricopharyngeal Muscle Dysfunction
• Patients make repeated, nonproductive 
efforts to swallow, gag, and cough, then 
forcibly regurgitate immediately after 
swallowing.
• Gag reflex and prehension are normal.
• Nasal reflux commonly observed when food 
hits closed PES.
• Coughing commonly observed secondary 
to aspiration pneumonia.
Esophageal Dysphagia
• Most common causes include mega -
esophagus, esophagitis, esophageal stricture, 
esophageal foreign bodies, and esophageal 
dysmotility.
• Diagnosis made with survey radiographs of 
thorax and neck followed by videofluoroscopic 
swallow assessment.
Gastroesophageal Dysphagia
Most common cause is sliding hiatal hernia in 
brachycephalic breeds, often associated with 
gastroesophageal reflux and subsequent 
CAUSES
• Anatomic or mechanical lesions include 
pharyngeal inflammation (e.g., abscess, 
inflammatory polyps, oral eosinophilic 
granuloma), neoplasia, pharyngeal and 
retropharyngeal foreign body, sialocele, 
temporomandibular joint disorders (e.g., 
luxation, fracture, craniomandibular 
osteopathy), mandibular fracture, cleft or 
congenitally short palate, cricopharyngeal 
muscle achalasia, lingual frenulum disorder, 
pharyngeal trauma.
• Pain as result of dental disease (e.g., tooth 
fractures and abscess), mandibular trauma, 
stomatitis, glossitis, and pharyngeal 
inflammation may disrupt normal prehension,

Canine and Feline, Seventh Edition  423
D
bolus formation, and swallowing. Stomatitis, 
glossitis, and pharyngitis may be secondary to 
feline viral rhinotracheitis, feline leukemia 
virus (FeLV)/feline immunodeficiency virus 
(FIV), pemphigus, systemic lupus 
erythematosus (SLE), uremia, and ingestion 
of caustic agents or foreign bodies.
• Neuromuscular disorders that impair 
prehension and bolus formation include CN 
deficits (e.g., idiopathic trigeminal neuro -
pathy CN V, lingual paralysis CN XII) and 
masticatory muscle myositis.
• Pharyngeal weakness, paresis, or paralysis 
can be caused by infectious polymyositis (e.g., 
toxoplasmosis and neosporosis), immune-
mediated polymyositis, muscular dystrophy, 
polyneuropathies, and myoneural junction 
disorders (e.g., myasthenia gravis, tick bite 
paralysis, botulism).
• Other CNS disorders, especially those 
involving the brainstem.
• Rabies can cause dysphagia by affecting 
both brainstem and peripheral nerves.
Many causative neuromuscular conditions 
have breed predispositions.
  DIAGNOSIS
• Differentiate vomiting from regurgitation.
• Vomiting is typically associated with 
abdominal contractions; dysphagia is not.
• Inflammatory conditions often cause a 
leukocytosis, sometimes with a left shift.
• High serum creatine kinase activity is 
usually suggestive of a myopathy.
• May find evidence of renal disease (e.g., 
azotemia and low urine concentration) in 
patients with oral and lingual ulcers 
secondary to uremia.
• Type 2M muscle antibody serology 
(masticatory muscle myositis).
• Acetylcholine receptor antibody serology 
(acquired myasthenia gravis).
• Antinuclear antibody serology (immune-
mediated diseases).
• T4, free T4, thyroid-stimulating hormone 
(TSH), anti-thyroglobulin antibodies to rule 
out hypothyroidism.
• Resting cortisol and/or adrenocorticotropic 
Addison’s disease.
IMAGING
• Obtain survey radiographs of thorax (3-views) 
and neck in all dysphagic animals for which oral 
cause of dysphagia has been ruled out.
• Ultrasonography of pharynx may be useful 
in patients with mass lesions and for obtaining 
ultrasound-guided biopsy specimens.• Fluoroscopy with barium is useful in 
evaluating pharyngeal and esophageal motility 
as well as proper coordination of upper and 
lower esophageal sphincters.
• CT and/or MRI for suspected intracranial 
mass.
• Esophagram (liquid barium administered 
orally followed by immediate survey radio  - 
graphs of the thorax) is helpful for diagnosing 
radiolucent esophageal foreign bodies and 
esophageal strictures, but is insensitive for 
diagnosing esophageal functional disorders.
• Endoscopy of nasopharynx—retroflexion of 
endoscope over soft palate to look for foreign 
bodies and evaluate esophagus and lower 
esophageal sphincter.
• Electromyography of skeletal musculature 
to confirm presence of myopathy.
• Repetitive nerve stimulation and edroph -
onium chloride (0.1–0.2 mg/kg IV) test for 
suspected myasthenia gravis.
• Cerebrospinal fluid analysis in patients with 
a CNS disorder.
Myopathies can be inflammatory or dystrophic.
  TREATMENT
• Determine underlying cause to optimize 
therapy and outcome.
• Most patients can be managed on 
outpatient basis unless there are other 
complicating factors such as aspiration 
pneumonia, dehydration, or weakness.
• Supportive care may be necessary if patient 
is dehydrated (IV fluids).
• Other supportive modalities may be 
necessary in case of aspiration pneumonia 
(oxygen, coupage, etc.).
• For patients with generalized weakness due 
to myopathies, good nursing care is required, 
such as rotating position, good padding, and 
physical therapy.
ACTIVITY
Alterations in activity should be based on 
DIET
• Nutritional support is important for all 
dysphagic patients, and consistency of diet 
should be altered to optimize swallowing in 
affected animals.
• Elevating head and neck during feeding and 
for 10–15 minutes after feeding may help 
patients with esophageal disease. Consider 
altering consistency of diet. Dogs with 
cricopharyngeal muscle dysfunction are able to 
handle kibble better than canned food or water.• If nutritional requirements cannot be met 
orally, gastrostomy tube may be necessary.
• Variable dependent on underlying cause.
• Educate the client that not all diseases can 
be cured, but managed.
• Changes in feeding (see above) may be long 
term.
• Clients should be taught to monitor for signs 
of possible aspiration pneumonia (mucopurulent 
nasal discharge, increased respiratory rate at rest, 
coughing, dyspnea, tachypnea).
• Cricopharyngeal myectomy (bilateral 
removal) may benefit patients with crico -
pharyngeal muscle dysfunction; correct 
diagnosis is essential using videofluoroscopy 
before surgery, and to rule out other myopathic 
or neuropathic causes of dysphagia.
• Hiatal hernia surgery generally involves 
left-sided gastropexy with esophageal hiatal 
plication and esophagopexy.
Dysphagia is not immediately life-
threatening; direct drug therapy at the 
• Use barium sulfate with caution in patients 
with evidence of aspiration.
• Use corticosteroids with caution or not at 
all in patients with evidence of, or at risk for, 
aspiration.
  FOLLOW-UP
• Daily for signs of aspiration pneumonia 
(e.g., lethargy, fever, mucopurulent nasal 
discharge, coughing, dyspnea).
• Body condition and hydration status daily; 
if oral nutrition does not meet requirements, 
use gastrostomy tube feeding.
Aspiration pneumonia and malnutrition.
• Megaesophagus.
• Malnutrition.(continued)  Dysphagia

424  Blackwell’s Five-Minute Veterinary Consult  
DAGE-RELATED FACTORS
• Puppies are more likely to have congenital 
abnormalities such as cricopharyngeal muscle 
achalasia, congenital megaesophagus, vascular 
ring anomalies, and cleft palates.
• Puppies with vascular ring anomalies will 
typically present with signs of regurgitation 
shortly after being weaned onto solid food at 
6–8 weeks of age.
• Puppies with cleft palates usually have milk 
or food refluxing from the nasal passage 
during mastication and swallowing.
• Puppies with cricopharyngeal muscle 
achalasia typically present with repeated 
bouts of swallowing, gagging, and retching 
during swallowing with nasal reflux of 
water or food.
• Puppies are more likely to ingest foreign 
objects that can lodge in the esophagus and 
cause esophagitis and stricture formation.
• Older dogs, in particular Labrador 
retrievers, are more likely to have esophageal 
dsymotility secondary to a polyneuropathy 
(geriatric onset laryngeal paralysis poly -
neuropathy or GOLPP).ZOONOTIC POTENTIAL
• Consider rabies in any patient with 
oropharyngeal dysphagia, especially if 
animal’s rabies vaccination status is unknown 
or questionable or it has been exposed to a 
potentially rabid animal.
• If a dysphagic animal dies of rapidly 
progressive neurologic disease, submit the 
head to a qualified laboratory designated by 
the local or state health department for rabies 
SEE ALSO
• Regurgitation.
• CN = cranial nerve.
• GOLPP = geriatric onset laryngeal paralysis 
polyneuropathy.
• PES = proximal esophageal sphincter.
• TSH = thyroid-stimulating hormone. Suggested Reading
Kook PH. Gastroesophageal reflux. In: 
Bonagura JD, T wedt DC, eds., Kirk’s 
Current Veterinary Therapy XV. St Louis, 
MO: Elsevier Saunders, 2014, pp. 501–504.
Marks SL. Oropharyngeal dysphagia. In: 
MO: Elsevier Saunders, 2014, pp. 495–500.
Pollard RE, Marks SL, Cheney DM. 
Diagnostic outcome of contrast 
videofluoroscopic swallowing studies in 216 
dysphagic dogs. Vet Radiol Ultrasound 
2017, 58(4):373–380.
Warnock JJ, Marks SL, Pollard R, et al. 
Surgical management of cricopharyngeal 
dysphagia in dogs: 14 cases (1989–2001). 
J Am Vet Med Assoc 2003, 
223(10):1462–1468.
available onlineDysphagia  (continued)

Canine and Feline, Seventh Edition  425
D
Dyspnea and Respiratory Distress
  BASICS
Dyspnea—a subjective term that in human 
medicine means “an uncomfortable sensation 
in breathing” or a sensation of air hunger; in 
veterinary medicine, it is used to indicate 
difficulty breathing or respiratory distress.
Dyspnea and respiratory distress are believed 
to occur when the CNS notes a difference 
between the afferent feedback from a given 
efferent motor drive signal (ventilation 
demanded) and what the brain had antici­
pated would be the appropriate afferent 
response (ventilation achieved).
Dogs and cats; age, breed, and sex predis­
position vary with inciting cause.
SIGNS
• Acute or chronic onset.
• Often associated with tachypnea, coughing, 
exercise intolerance, lethargy, inappetence.
• General signs of respiratory distress—
tachypnea, increased abdominal effort, nasal 
flaring, open ­mouth breathing, cyanosis, 
orthopnea (neck extension, elbow abduction), 
altered mentation; other signs depend on 
• Nasal disease—stertor, nasal discharge, lack 
of airflow through nostrils; dyspnea improves 
with open ­mouth breathing.
• Upper airway/laryngeal disease—stridor, 
panting, cough, hyperthermia, dysphonia, 
respiratory effort and noise on inspiration, 
fixed obstruction such as a mass or foreign 
body in a large airway: dyspnea on inspiration 
and expiration.
• T racheal collapse—honking cough, tracheal 
sensitivity, respiratory effort and noise: 
inspiratory effort if cervical tracheal collapse, 
expiratory effort if intrathoracic tracheal 
collapse.
• Lower airway disease—cough, expiratory 
wheezes on auscultation, abdominal effort.
• Pulmonary parenchymal disease—may have 
crackles, harsh or moist lung sounds on 
auscultation.
• Pneumonia—fever, may have tracheal 
• Cardiogenic pulmonary edema—heart 
murmur, arrhythmia, hypothermia, pale 
mucous membranes, prolonged capillary 
refill time.
• Pleural space disease—diminished breath 
sounds: ventrally—fluid; dorsally—air; 
unilaterally—space ­occupying lesions or pyothorax/chylothorax. Paradoxical 
respiratory pattern (inward movement of the 
abdominal wall during inspiration).
• Thoracic wall disease—can have paradoxical 
respiratory pattern, visible or palpable trauma 
(open pneumothorax, flail chest).
• Pulmonary thromboembolism (PTE)—
may have clinical signs of underlying disease 
predisposing to thrombosis, e.g., hyperadreno­
corticism, immune ­mediated hemolytic 
anemia (IMHA), systemic inflammatory 
response syndrome (SIRS)/sepsis, protein ­
losing nephropathy (PLN), protein ­losing 
enteropathy (PLE), neoplasia.
• Other signs will pertain to the underlying 
disease, e.g., shock, trauma.
Upper Airway Disease
• Nasal obstruction—stenotic nares, 
nasopharyngeal polyp or stenosis, infection, 
inflammation, neoplasia, trauma, foreign 
body, coagulopathy.
• Pharynx—elongated soft palate, foreign 
body, neoplasia, granuloma, stenosis.
• Larynx—laryngeal paralysis, everted 
laryngeal saccules, edema, collapse, foreign 
body, neoplasia, inflammation, trauma, 
webbing.
• T rachea—collapse, stenosis, trauma, foreign 
body, neoplasia, parasites, extraluminal 
compression (lymphadenopathy, enlarged left 
atrium, heart ­base tumors).
Lower Airway Disease
Allergic disease, inflammatory, infectious 
(Mycoplasma ), parasitic, neoplastic 
(bronchogenic carcinoma).
Pulmonary Parenchymal Disease
• Edema—cardiogenic or noncardiogenic.
• Pneumonia—infectious; parasitic; 
aspiration; eosinophilic; interstitial.
• Neoplasia (primary or metastatic).
• Inflammatory— acute respiratory distress 
syndrome (ARDS); uremic pneumonitis; 
smoke inhalation.
• Hemorrhage—trauma; coagulopathy.
• PTE—IMHA; PLN, PLE; heartworm 
disease; hyperadrenocorticism; neoplasia.
• Others—lung lobe torsion, atelectasis.
Pleural Space Disease
• Pneumothorax—traumatic; iatrogenic; 
secondary to pulmonary parenchymal disease; 
ruptured bulla; migrating foreign body; 
primary spontaneous (no underlying cause).
• Pleural effusion—transudates, exudates; 
hemothorax; chylothorax.
• Soft tissue—neoplasia; diaphragmatic hernia.
• Fibrosing pleuritis.
Thoracic Wall Disease
• Open pneumothorax—trauma.
• Flail segment—trauma.
• Paralysis due to cervical spinal disease, 
botulism, polyradiculoneuritis, tick bite paralysis, myasthenia gravis, elapid snake 
envenomation, hypokalemia.
Diaphragmatic Disease
• T rauma—rupture; hernia.
• Phrenic nerve disease.
• Fibrosis.
Abdominal Distention
Organomegaly—hyperplasia; neoplasia, 
pregnancy; obesity; ascites; gastric dilatation, 
torsion.
  DIAGNOSIS
• Inspiratory dyspnea—suggests extrathoracic 
upper airway disease.
• Expiratory dyspnea—suggests intrathoracic 
airway disease.
• Dyspnea on inspiration and expiration can 
occur with fixed upper airway obstructions 
and severe intrathoracic disease.
• Congestive heart failure—murmur, 
arrhythmia, tachycardia, poor pulse quality, 
jugular pulses, hypothermia, crackles on 
auscultation, fluid dripping from nose.
• Anemia—can cause nonrespiratory 
dyspnea.
• Polycythemia—chronic hypoxia.
• Inflammatory leukogram—pneumonia, 
pneumonitis, pyothorax.
• Eosinophilia—hypersensitivity or parasitic 
• Thrombocytosis—hyperadrenocorticism 
predisposes to PTE.
• Sodium : potassium ratio <27—can be seen 
with pleural or abdominal effusions.
• Azotemia—if severe may lead to uremic 
pneumonitis.
• Proteinuria—can predispose to PTE.
• Multiple organ dysfunction—ARDS.
• Hypoproteinemia—may suggest protein ­
losing disease that can predispose to PTE or 
• Pleural fluid analysis.
• Fecal examination for parasites if  
indicated
• Serum antigen or antibody titers—
heartworm, toxoplasmosis, distemper, feline 
leukemia virus (FeLV), feline immuno­
• Increased urine protein : creatinine ratio 
with PLN could indicate loss of antithrombin 
and hypercoagulability resulting in PTE.
• PaO2—partial pressure of oxygen dissolved 
in arterial blood; normoxemia: PaO2 
80–120 mmHg (room air, sea level); 
hypoxemia: PaO2 <80 mmHg; FIO2—
fraction of inspired oxygen ranges from 0.21 
(room air) to 1.0; PaO2/FIO2 ratio—measure

426  Blackwell’s Five-Minute Veterinary Consult  
Dof lung efficiency during oxygen therapy; 
PaO2/FIO2 ≥400—normal lung efficiency; 
300–400—mild insufficiency; 200–300—
moderate insufficiency; <200—severe 
insufficiency. Reduction in lung efficiency 
can be due to venous admixture, hypo­
ventilation, low inspired oxygen.
• PaCO2 or PvCO2—partial pressure of 
CO2 dissolved in arterial or venous blood; 
measure of ventilation; normal 30 mmHg 
<PCO2 <40 mmHg. PCO2 > 45 mmHg = 
hypercapnia = hypoventilation = decreased 
alveolar minute ventilation (MV).
• Coagulation testing—if suspect hemothorax 
and/or pulmonary hemorrhage.
• Plasma NT ­proBNP and cardiac troponin ­I 
(cTNI) concentrations may aid in different­
iation of cardiac and noncardiac causes of 
dyspnea.
IMAGING
• Cervical and thoracic radiography—upper 
airway disease: soft palate elongation, large 
airway narrowing, lymphadenopathy, 
intraluminal abnormalities. Lower airway 
disease: bronchial thickening, middle lung 
lobe consolidation (cats), atelectasis, hyper­
inflation, and diaphragmatic flattening 
(primarily cats). Pneumonia: alveolar 
infiltrates; aspiration pneumonia usually 
cranioventral distribution or middle lobe 
affected. Cardiogenic pulmonary edema: 
enlarged cardiac silhouette, pulmonary venous 
distention, enlarged left atrium with perihilar 
pulmonary infiltrates in dogs; infiltrates can 
be of any distribution in cats. Noncardiogenic 
pulmonary edema: usually caudodorsal 
distribution. ARDS: diffuse, symmetric 
alveolar infiltrates. Pulmonary vascular 
abnormalities: PTE, heartworm disease. 
Pleural space disease: pneumothorax, pleural 
effusion, mass lesions, diaphragmatic hernias. 
Thoracic wall disease: rib fractures, neoplasia.
• Thoracic ultrasonography—evaluation of 
distribution of pleural effusion, pneumothorax 
(absence of “glide sign”), and parenchymal 
disease (presence of “comet tail” artifact). 
Pulmonary mass identification: guide 
fine­needle aspiration; mediastinal evaluation.
• Echocardiography—evaluate cardiac 
function and chamber size if cardiogenic 
pulmonary edema or pleural effusion 
suspected; elevated pulmonary artery pressure, 
right ventricular overload with ventricular 
septal flattening can support diagnosis of 
PTE; visualize heart ­based masses.
• Abdominal radiography or ultrasound—
evaluation of abdominal distention.
• Fluoroscopy—evaluate tracheal and 
bronchial collapse; evaluate diaphragmatic 
function.
• CT—airway, pulmonary parenchymal, and 
pleural space disease can be evaluated; can 
detect lesions not clearly defined on radio ­ 
graphs.• Pulmonary vascular angiography—gold 
standard for diagnosis of PTE.
• Ventilation perfusion scintigraphy—
abnormal perfusion scan is considered 
supportive of PTE.
• Pulse oximetry—SpO2; peripheral capillary 
hemoglobin oxygen saturation. The relation­
ship between PaO2 and SpO2 is defined by 
the oxygen hemoglobin dissociation curve: 
PaO2 of 60 mmHg = SpO2 of 90%; PaO2 of 
80 mmHg = SpO2 of 95%; PaO2 of 
>100 mmHg = SpO2 of 100%. Below 95%, 
small changes in SpO2 signify large changes in 
PaO2. SpO2 measurements in animals on high 
inspired oxygen lack sensitivity.
• Thoracentesis—fluid analysis and culture.
• Laryngoscopy/nasopharyngoscopy/
tracheoscopy—evaluate upper airway; 
laryngeal paralysis, tracheal collapse, foreign 
bodies, masses.
• Bronchoscopy—evaluate upper and lower 
airways; perform bronchoalveolar lavage for 
cytology and culture. Requires anesthesia, 
perform only when stabilized.
  TREATMENT
• Inpatient care until the cause is identified 
and treated or determined not to be life ­ 
threatening; therapy dependent on underlying 
cause.
• Always  administer oxygen and keep patient 
in sternal recumbency until ability to 
oxygenate is determined.
• May require intubation and positive ­pressure 
ventilation in patients with severe respiratory 
distress refractory to oxygen therapy.
• Upper airway disease—use sedation to reduce 
respiratory effort. Check body temperature and 
actively cool patients as needed.
• Lower airway disease—bronchodilators; 
systemic corticosteroids may be required to 
stabilize cats with acute bronchoconstriction.
• Pulmonary parenchymal disease—
antibiotics if pneumonia; treat coagulation 
disorders; cardiogenic edema requires 
furosemide ± vasodilators. Noncardiogenic 
edema requires oxygen therapy, may require 
positive ­pressure ventilation.
• Pleural space disease—thoracocentesis for 
air and fluid. Place a chest tube if repeated 
thoracocentesis is necessary to keep patient 
stable.
• Thoracic wall disease—surgery as indicated, 
particularly if open chest wound is present; 
flail chest may require surgery if medical 
management fails or there is a severe 
displacement of fractures. Thoracic wall 
paralysis/muscle fatigue: positive ­pressure 
ventilation if severely hypercapnic.• Abdominal distention—drain ascites as 
needed; relieve gastric distention.
• Oxygen therapy via cage, nasal cannula, 
Elizabethan collar covered in plastic wrap, 
mask, or flow ­by. Humidify oxygen source if 
giving oxygen therapy for more than a few 
hours.
• Maintain in sternal recumbency and turn 
hips every 3–4 hours if patient cannot tolerate 
lateral recumbency.
• Monitor temperature regularly, as excess 
work of breathing results in hyperthermia, 
which augments respiratory distress.
DIET
Weight ­reducing diet if obesity is a 
contributing cause.
• Anesthesia must be carefully tailored to the 
patient. Securing an airway is essential and 
rapid intravenous induction is important. 
The ability to positive ­pressure ventilate 
patients is often required.
• Animals with upper airway obstruction 
are fragile and can rapidly decompensate. 
Have multiple ­sized endotracheal tubes 
• Dyspnea associated with a laryngeal mass can 
respond to debulking surgery, but edema and 
hemorrhage can lead to worsened obstruction. 
Warn owners of increased likelihood of 
aspiration pneumonia complications in 
animals with laryngeal disease.
• Avoid positive ­pressure ventilation in 
patients with a closed pneumothorax. Must 
monitor oxygenation status of anesthetized 
patients with pulse oximetry and when 
possible arterial blood gases.
Varies with underlying cause (see Appropriate 
Health Care).
  FOLLOW-UP
• Patients receiving oxygen therapy can be 
monitored by assessing the degree of 
respiratory effort. As the animal stabilizes, 
perform a room air trial and reevaluate the 
level of respiratory difficulty. Arterial and 
venous blood gases can be a useful assessment.
• Pulse oximetry is an effective and 
noninvasive tool for monitoring patients on 
room air.
• Repeat radiographs are often indicated in 
assessing pulmonary parenchymal disease and 
pleural space disease.Dyspnea and Respiratory Distress  (continued)

Canine and Feline, Seventh Edition  427
D
   MISCELLANEOUS
SEE ALSO
• Acute Respiratory Distress Syndrome.
• Brachycephalic Airway Syndrome.
• Congestive Heart Failure, Left ­Sided.
• Congestive Heart Failure, Right ­Sided.
• Laryngeal Diseases.
• Pneumonia, Aspiration.
• Pulmonary Edema, Noncardiogenic.
• ARDS = acute respiratory distress 
syndrome.
• cTNI = cardiac troponin ­I.
• FeLV = feline leukemia virus.• FIO2 = fraction of inspired oxygen.
• IMHA = immune ­mediated hemolytic 
anemia.
• MV = minute ventilation.
• PaCO2 = partial pressure of carbon  
dioxide.
• PLE = protein ­losing enteropathy.
• PLN = protein ­losing nephropathy.
syndrome.
Herndon WE, Rishniw M, Schrope D, et al. 
Assessment of plasma cardiac troponin I 
concentration as a means to differentiate 
cardiac and noncardiac causes of dyspnea in 
cats. JAVMA 2008, 233:1261–1264.Mellema MS. The neurophysiology of dyspnea. 
J Vet Emerg Crit Care 2008, 18:561–571.
Rozanski E. Respiratory distress. In: Drobatz 
KJ, Hopper K, Rozanski EA, et al. Textbook 
of Small Animal Emergency Medicine. 
Hoboken, NJ: Wiley, 2018, pp. 18–21.
Smith KF , Quinn RL, Rahilly LJ. Biomarkers 
for differentiation of causes of respiratory 
distress in dogs and cats: Part 1 – Cardiac 
disease and pulmonary hypertension. J Vet 
Emerg Crit Care 2015, 25(3):311–329.
Author  Yu Ueda
Acknowledgement  The author and book 
Kate Hopper.
available online(continued)  Dyspnea and Respiratory Distress

428  Blackwell’s Five-Minute Veterinary Consult  
DDystocia
  BASICS
Difficult birth.
• Dystocia may occur due to maternal or fetal 
factors and may occur during any stage of labor.
• May be caused by abnormal fetal present­
ation, posture, or position.
• Normal stages of labor:
Stage 1
• Onset of uterine contractions and relax  ­ 
ation of cervix; ends with rupture of first 
chorioallantoic sac—averages 6–12h (up to 
36h in primiparous bitch).
• Bitch—may be restless, nervous, shiver, 
pant, pace, and nest.
• Queen—tend to vocalize initially; purr and 
socialize as Stage 1 progresses.
Stage 2
• Delivery of fetuses.
• Bitch—obvious abdominal contractions; 
beginning of stage 2 to delivery of first 
offspring usually <4h; average time to 
delivery of subsequent fetus 20–60 min (may 
be as long as 2–3h).
• Queen—average length of parturition 16h, 
with range of 4–42h (up to 3 days in some 
cases); important to consider this variability 
when intervening.
• Number of fetuses present may significantly 
affect length of stages 2 and 3.
Stage 3
• Delivery of fetal membranes.
• May alternate between stage 2 and 3 with 
multiple fetuses.
• Dog—incidence unknown due to breed 
variability and breeder intervention.
• Cat—3.3–5.8% of parturitions; mixed ­
breed cats 0.4%, higher in pedigree cats, to 
18.2% in Devon Rex.
Dogs
• Higher incidence with miniature and small 
breeds (small litter size, concurrent large fetal 
size); may occur in large breeds with large or 
singleton litters.
• Brachycephalic breeds—broad head and 
narrow pelvis.
• Large fetal head : maternal pelvis ratio—
Sealyham terrier, Scottish terrier.
• Uterine inertia—Scottish terrier, dachshund, 
border terrier, Aberdeen terrier, Labrador 
retriever.
• Other breeds with increased incidence of 
dystocia—chihuahua, dachshund, Pekingese, 
Yorkshire terrier, miniature poodle, 
Pomeranian.Cats
Brachycephalic (Persian, Himalayan) or 
dolichocephalic (Devon Rex) breeds.
SIGNS
• More than 30 min of persistent, strong, 
abdominal contractions without fetal delivery.
• More than 4h from onset of stage 2 to 
delivery of first fetus (bitch).
• More than 2h between delivery of fetuses 
(bitch).
• Failure to commence stage 1 labor within 
24h of rectal temperature drop below 37.2 °C 
(99 °F) or within 36h of serum progesterone 
concentration <2 ng/mL (bitch).
• Female cries, displays signs of pain, and 
constantly licks vulvar area when contracting.
• Prolonged gestation—more than 72 days 
from day of first mating (bitch); more than 
59 days from first day of cytologic diestrus 
(bitch); more than 66 days from luteinizing 
hormone (LH) peak (bitch); more than 68 
days from last day of mating (queen).
• Presence of greenish ­black discharge 
(uteroverdin) preceding birth of first fetus by 
more than 2h or increasing amounts before 
delivery of first fetus.
• Bloody discharge prior to delivery of first fetus.
• Diminished or absent Ferguson’s reflex 
(stimulation or pressure to dorsal vaginal wall 
to elicit abdominal straining: “feathering”) 
indicates uterine inertia.
CAUSES
Fetal
• Oversize; fetal monsters, fetal anasarca, fetal 
hydrocephalus, prolonged gestation due to 
inability of singleton fetus to initiate labor.
• Abnormal presentation, position, or posture 
of fetus in birth canal.
• Fetal death.
Maternal
• Inadequate uterine contractions (primary or 
secondary uterine inertia)—myometrial 
defect, hypocalcemia electrolyte imbalance, 
psychogenic disturbance, exhaustion.
• Ineffective abdominal press—pain, fear, 
debility (exhaustion), diaphragmatic hernia, age.
• Placentitis, metritis, endometritis.
• Pregnancy toxemia, gestational diabetes.
• Abnormal pelvic canal—previous pelvic injury, 
abnormal conformation, pelvic immaturity.
• Congenitally small pelvis—Welsh corgis, 
brachycephalic breeds.
• Inguinal hernia.
• Abnormality of vaginal vault—stricture, 
septae, vaginal hyperplasia, hypoplastic 
vagina, intra ­ or extraluminal cysts, neoplasia.
• Abnormal vulvar opening—stricture, 
fibrosis from trauma, neoplasia.
• Insufficient cervical dilation.
• Lack of adequate lubrication.
• Uterine torsion.• Uterine rupture.
• Uterine neoplasia, cysts, or adhesions.
• Age.
• Brachycephalic and toy breeds.
• Persian, Himalayan, and Devon Rex breeds.
• Obesity.
• Abrupt changes in peripartum 
• Previous history of dystocia.
  DIAGNOSIS
Uterine inertia—hypocalcemia versus 
hypoglycemia.
• Complete physical examination—careful 
abdominal palpation to confirm presence of 
fetuses.
• Digital vaginal examination—fetus or fetal 
membranes in vaginal canal, assess maternal 
pelvic canal, Ferguson’s reflex.
• Bitch unresponsive to oxytocin or lacking 
Ferguson’s reflex—uterine inertia more likely 
than obstructive dystocia unless obstructed 
for several hours.
Minimum database—packed cell volume 
(PCV), total protein, serum glucose, urea 
nitrogen, and calcium (ionized preferable to total 
concentration corrected for albumin) concentra ­
tions. Pregnant females have mild anemia.
Serum progesterone concentration.
IMAGING
• Radiography—determine pelvic 
conformation, number and position of fetuses, 
evidence of fetal obstruction, oversize, or death.
• Fetal death—collapse of fetal skeletons, 
abnormal association of fetal bones to axial 
skeleton, presence of air/gas surrounding 
fetus, fetal balling.
• Ultrasonography—recommended for 
monitoring fetal viability, heart rate (fetal 
heart rate <180 bpm indicates fetal stress, 
>260 bpm indicates need for close 
monitoring), placental separation, and 
character of fetal fluids (presence of 
meconium or blood in amniotic fluid).
  TREATMENT
• Inpatient—until delivery of all fetuses and 
dam is stable.
• T reat hypoglycemia and hypocalcemia.
• Uterine inertia—medical treatment if no 
evidence of fetal stress.

Canine and Feline, Seventh Edition  429
D
• Ecbolic agents contraindicated with 
possible obstructive dystocia—may accelerate 
placental separation and fetal death or cause 
uterine rupture.
• WhelpWise® tocodynamometer monitors 
fetal heart rates and uterine contraction 
patterns; useful for bitches with large litters or 
history of uterine inertia to determine need 
for intervention.
Manual Delivery
Fetus lodged in vaginal vault:
• Lubricate liberally.
• Digital manipulation—least amount of 
damage to fetus and dam. Apply traction in 
postero ­ventral direction.
• Instrument delivery not recommended due 
to inadequate space—may mutilate fetus or 
lacerate dam.
• Never apply traction to distal extremities or 
tail of a live fetus.
• Failure to deliver fetus located in vaginal 
canal within 30 min—Cesarean section 
(C­section) indicated.
• Indications for C ­section—uterine inertia 
unresponsive to oxytocin or uterine inertia 
with more than four fetuses remaining in 
utero (maximizes fetal survivability), pelvic or 
vaginal obstruction, inability to correct fetal 
malposition, fetal oversize, fetal stress, in 
utero fetal death.
• Elective C ­section—breeds prone to 
dystocia, bitches with a history of dystocia, 
bitches with singleton or large litter size, 
performed to maximize fetal survivability.
• Provide fluid therapy with balanced electrolyte 
solution before, during, and after surgery.
• Gravid uterus can compress great vessels and 
place pressure on diaphragm, compromising 
venous return and tidal volume.
• Preoxygenation of patient before anesthesia 
is indicated.
• Anesthetic protocol for C ­section:
◦ Premedication can include glycopyrrolate 
(bitches, queens: 0.01 mg/kg IV/IM) if fetal 
heart rates are normal; or atropine (bitches, 
queens: 0.04 mg/kg IM) if fetal bradycardia 
present.
◦ Alpha ­2 agonist agents (xylazine, 
dexmedetomidine) are contraindicated.
◦ Rapidly acting induction agents include 
propofol or alfaxalone; ketamine may cause 
dose­dependent neonatal respiratory and 
neurologic depression; severely depressed or 
exhausted patients may be induced with 
combination of opioid and benzodiazepine with supplemental propofol or alfaxalone 
for intubation, if needed.
◦ Maintenance may include inhalant 
anesthetics or propofol IV CRI.
◦ Use of a midline lidocaine line block 
(1–2 mg/kg SC) can decrease inhalant 
anesthetic requirement.
• Epidural—0.5% bupivacaine (0.2 mg/kg) 
and preservative ­free morphine (0.1 mg/kg) 
or 2% lidocaine (2–4 mg/kg).
• Postoperative analgesia may be provided 
with opioids, although they are excreted in 
the milk to varying degrees.
• Reversal agents—repeated dosing may be 
necessary until neonate has processed all 
anesthetic drugs:
◦ Opioids used during anesthesia can be 
reversed in neonate with naloxone (0.04 mg/
kg IV/IM/SC/sublingual/intranasal).
◦ Benzodiazepines used during anesthesia can 
be reversed in neonate with flumazenil (0.01 
mg/kg IV/IM/SC/sublingual/intranasal).
• Hypoglycemia—treat prior to hypo  ­ 
calcemia:
◦ Bolus 0.5 g/kg IV (diluted 1 : 3).
◦ Add 5% dextrose to balanced electrolyte 
solution and infuse IV at 60–80 mL/kg/day.
• Hypocalcemia:
◦ Bitch—10% calcium gluconate 0.2 mL/
kg IV over 10 min; monitor for 
bradycardia. Repeat q4–6h as needed.
◦ May also be given SC at a dose of 0.5 
mL/4.5 kg diluted 1:1 with sterile saline.  
If using 23% solution, dilute at least 1:3 
prior to administration.
◦ Queen—10% calcium gluconate 
0.5–1.0 mL/cat IV over 10 min—use with 
caution; risk of uterine rupture increased 
due to strong uterine contractions following 
calcium.
• Oxytocin—once calcium and glucose 
deficits are treated: microdose at 0.5–3.0 IU 
IM/SC depending on size of bitch and 
response to treatment. May repeat q30 min as 
long as delivery progresses. Consider 
C­section if more than three doses of 
oxytocin per fetus are required or more than 
four fetuses remain.
Oxytocin—contraindicated with obstructive 
dystocia, fetal stress, longstanding in utero 
fetal death, uterine rupture, uterine torsion.  FOLLOW-UP
• Schedule elective C ­section for bitches with 
abnormal pelvic canal, anatomic 
abnormalities, predisposition to dystocia, 
previous history of uterine inertia.
• Scheduling surgery—extremely important 
that D1 diestrus, LH peak, or ovulation is 
identified during breeding to ensure 
acceptable fetal survivability. If ovulation 
timing is not available, ultrasonographic 
gestational aging and maturation assessment 
is necessary.
• If dystocia is identified promptly and 
intervention is successful—good to fair for 
survival of dam; fair for fetuses.
• If dystocia unrecognized or untreated for 
24–48h—poor to guarded for life of dam; 
fetal survival unlikely.
Dystocia may or may not impact future 
fertility, but may recur depending on cause. 
Resolution of dystocia by C ­section does not 
preclude natural whelping for future 
deliveries.
SEE ALSO
• Uterine Inertia.
• C­section = Cesarean section.
Johnston SD, Root Kustritz MV, Olson PNS. 
Canine parturition; Feline parturition. In: 
Philadelphia, PA: Saunders, 2001, 
pp. 105–128, 431–437.
Author  Cheryl Lopate
available online(continued)  Dystocia

430  Blackwell’s Five-Minute Veterinary Consult  
DDysuria, Pollakiuria, and Stranguria
  BASICS
• Dysuria—difficult or painful urination.
• Pollakiuria—voiding small quantities of 
urine with increased frequency.
• Stranguria—straining to urinate.
The urinary bladder and urethra normally 
serve as a reservoir for urine. Inflammatory 
and noninflammatory disorders of the lower 
urinary tract including the urethral orifice 
may decrease bladder compliance and storage 
capacity by damaging structural components 
of the bladder wall or by stimulating sensory 
nerve endings located in the bladder or 
urethra. Sensations of bladder fullness, 
urgency, and pain stimulate premature 
micturition and reduce functional bladder 
capacity. Dysuria and pollakiuria are caused 
by lesions of the urinary bladder and/or 
urethra and provide unequivocal evidence of 
lower urinary tract disease; these clinical signs 
do not exclude concurrent involvement of the 
upper urinary tract or disorders of other body 
systems. Stranguria may be caused by bladder, 
intraluminal, and extraluminal urethral 
disease.
Renal/urologic/pelvic structures—bladder, 
urethra, prostate gland, colon, others.
CAUSES
Urinary Bladder
• Urinary tract infection (UTI)—bacterial, 
fungal, mycoplasmal, parasitic, or viral.
• Cystolithiasis.
• Neoplasia—e.g., transitional cell carcinoma.
• T rauma.
• Anatomic abnormalities—e.g., ureterocele/
urethrocele, ectopic ureter, persistent uterus 
masculinus, perineal hernias containing the 
urinary bladder, and spay granulomas.
• Detrusor atony—e.g., chronic partial 
obstruction, neurologic damage, and dysaut- 
onomia.
• Chemicals/drugs—e.g., cyclophosphamide.
• Iatrogenic—e.g., catheterization, palpation, 
reverse flushing, overdistension of the bladder 
during contrast radiography, urohydro -
propulsion, urethrocystoscopy, and surgery/
interventional hardware (e.g., ureteral stent, 
subcutaneous ureteral bypass, stent, hydraulic 
occluder).
• Idiopathic—e.g., feline idiopathic cystitis.
Urethra
• UTI—see above.
• Urethrolithiasis—see above.
• Urethral plugs—e.g., matrix and 
matrix-crystalline.• Neoplasia—see above; local invasion by 
malignant neoplasms of adjacent structures.
• T rauma.
• Anatomic anomalies—e.g., congenital or 
acquired strictures, urethrorectal fistulas, 
pseudohermaphrodites.
• Urethral sphincter hypertonicity—e.g., 
upper motor neuron spinal cord lesions, reflex 
dyssynergia, urethral spasm/urethritis.
• Proliferative urethritis—secondary to 
chronic UTI.
Prostate Gland
• Prostatitis, prostatic, or paraprostatic cyst or 
prostatic abscess.
• Neoplasia—adenocarcinoma, transitional 
• Diseases, diagnostic procedures, or treat  - 
ments that alter normal host urinary tract 
defenses and predispose to infection, 
predispose to formation of uroliths, or 
damage urothelium or other tissues of lower 
urinary tract.
• Mural or extramural diseases that compress 
bladder or urethral lumen.
• Diseases that encourage repeated urination 
despite full void such as juvenile vaginitis may 
present as stranguria.
  DIAGNOSIS
Differentiating from Other Abnormal 
Patterns of Micturition
• Polyuria—increased frequency and volume 
of urine >2 mL/kg/h and urine specific 
gravity <1.025.
• Rule out urethral obstruction—anuria, 
overdistended urinary bladder, signs of 
postrenal uremia.
• Urinary incontinence—involuntary 
urination, urine dribbling, enuresis, 
• Behavioral causes.
Differentiate Causes of Dysuria, 
Pollakiuria, Stranguria
• Rule out UTI—hematuria; malodorous or 
cloudy urine; small, painful, thickened bladder 
(also evaluate for mineralization or gas in wall).
• Rule out urolithiasis—hematuria; palpable 
uroliths in urethra or bladder.
• Rule out neoplasia—hematuria; palpable 
masses in urethra or bladder.
• Rule out neurogenic disorders—flaccid 
bladder wall; residual urine in bladder 
lumen after micturition; other neurologic 
deficits to hind legs, tail, perineum, and 
anal sphincter.
• Rule out prostatic diseases—urethral 
discharge, prostatomegaly, pyrexia, depression, 
tenesmus, caudal abdominal pain, stiff gait.• Rule out colorectal disease for stranguria.
• Rule out cyclophosphamide cystitis— 
history.
• Rule out iatrogenic disorders—history of 
catheterization, reverse flushing, contrast 
radiography, urohydropropulsion, urethro -
cystoscopy, or surgery/complications from 
interventional devices.
• Results of bloodwork often normal. 
Lower urinary tract disease complicated by 
urethral obstruction may be associated 
with azotemia, hyperphosphatemia, 
acidosis, and hyperkalemia. Patients with 
concurrent pyelonephritis may have 
impaired urine-concentrating capacity, 
leukocytosis, azotemia, and thrombo -
cytopenia if ureteral obstruction occurs 
concurrently. Patients with acute 
prostatitis or prostatic abscesses may have 
leukocytosis, discospondylitis, and/or heart 
murmur. Dehydrated patients may have 
elevated total plasma protein.
• Disorders of urinary bladder are best 
evaluated with urine specimen collected by 
cystocentesis. Urethral disorders best 
evaluated with mid-catch voided urine sample 
or by comparison of results of analysis of 
voided and cystocentesis samples. (Caution: 
cystocentesis may induce hematuria.)
• Pyuria, hematuria, and proteinuria indicate 
urinary tract inflammation, but are 
nonspecific findings that may result from 
infectious and noninfectious causes of lower 
urinary tract disease.
• Identification of bacteria, fungi, or parasite 
ova in urine sediment suggests, but does not 
prove, that UTI causing or complicating 
lower urinary tract disease. Consider 
contamination of urine during collection and 
storage when interpreting urinalyses.
• Identification of neoplastic cells in urine 
sediment indicates urinary tract neoplasia. 
Use caution in establishing diagnosis of 
neoplasia based on urine sediment exam -
ination. Urinary tract inflammation or 
extremes in urine pH or osmolality can cause 
epithelial cell atypia that is difficult to 
differentiate from neoplasia. Follow up with 
traumatic catheterization, cystoscopic 
biopsies, or urine BRAF assay.
• Crystalluria occurs in normal patients, 
patients with urolithiasis, or patients with lower 
urinary tract disease unassociated with uroliths. 
Interpret significance of crystalluria cautiously.
• Hematuria, proteinuria, and variable 
crystalluria occur in cats with nonobstructive 
idiopathic cystitis. Significant pyuria is rare.
• Quantitative urine culture—most definitive 
means of identifying and characterizing 
bacterial UTI. If not affordable then rapid 
culture can still be performed for species 
identification at limited cost.

Canine and Feline, Seventh Edition  431
D
• Cytologic evaluation of urine sediment, 
prostatic fluid, urethral or vaginal discharges, 
or biopsy specimens obtained by catheter or 
needle aspiration—may help in evaluating 
patients with localized urinary tract disease; 
may establish definitive diagnosis of urinary 
tract neoplasia, but cannot rule it out.
IMAGING
Survey abdominal radiography, urinary tract 
ultrasonography, cystoscopy, and fluoroscopic 
urography are important means of identifying 
and localizing causes of dysuria, pollakiuria, 
and stranguria.
• Use cystoscopy in patients with persistent 
lesions of lower urinary tract for which no 
definitive diagnosis has been established by 
other, less invasive means.
• Use light microscopic evaluation of tissue 
biopsy specimens from patients with persistent 
lesions of urinary tract. Tissue specimens may 
be obtained by traumatic catheterization, 
cystoscopy and biopsy, or surgery.
  TREATMENT
• Patients with nonobstructive lower urinary 
tract diseases typically managed as outpatients; 
diagnostic evaluation may require brief 
• Dysuria, pollakiuria, and stranguria 
associated with systemic signs of illness (e.g., 
pyrexia, depression, anorexia, vomiting, and 
dehydration) or laboratory findings of 
azotemia or leukocytosis warrant aggressive 
diagnostic evaluation and initiation of 
supportive and symptomatic treatment.
• T reatment depends on underlying cause 
and specific sites involved.
• Clinical signs of dysuria, pollakiuria often 
resolve rapidly following specific treatment of 
underlying cause(s). If not related to infection, 
stranguria may be more challenging to resolve.
• Patients with urge incontinence, severe or 
persistent signs, or untreatable lower urinary tract disease may benefit from 
symptomatic therapy with propantheline or 
oxybutynin that may reduce the force and 
frequency of uncontrolled detrusor 
contractions.
• Propantheline—dogs: 0.2 mg/kg PO 
q6–8h; cats: 0.25–0.5 mg/kg PO q12–24h. 
Oxybutynin—dogs: 0.2 mg/kg PO q8–12h; 
cats: 0.5–1.25 mg/cat PO q8–12h.
• Stranguria due to physiologic causes may be 
treated with prazosin in female dogs or cats, 
or in male dogs or cats with tamsulosin. If 
secondary to inflammation, meloxicam or 
carprofen can be utilized (caution with 
elevated liver values and azotemia), although 
short-term catheterization may also be 
• Patients with transitional cell carcinoma of 
the urinary bladder or urethra may be treated 
with piroxicam (0.3 mg/kg PO q24h), which 
reduces the severity of clinical signs, improves 
quality of life, and in some cases induces 
tumor remission. Chemotherapeutic and 
radiation oncology treatment options are also 
available, as is urethral stenting.
• Glucocorticoids or other 
immunosuppressive agents in patients 
suspected of having urinary or genital tract 
• Potentially nephrotoxic drugs (e.g., 
gentamicin) in patients that are febrile, 
dehydrated, or azotemic or that are suspected 
of having pyelonephritis, septicemia, or 
preexisting renal disease.
N/A
N/A
N/A
  FOLLOW-UP
Monitor response to treatment by status of 
clinical signs, serial physical examination, 
laboratory testing, and imaging evaluations 
appropriate for each specific case.POSSIBLE COMPLICATIONS
• Dysuria and pollakiuria may be associated 
with formation of macroscopic vesicourachal 
diverticula.
• Refer to specific chapters describing diseases 
listed under Causes.
• Hematuria, pyuria, and proteinuria.
• Disorders predisposing to UTI.
• Disorders predisposing to formation of 
uroliths.
• Macroscopic vesicourachal diverticula.
SYNONYMS
• Feline urological syndrome.
• Lower urinary tract disease.
SEE ALSO
• Feline Idiopathic Lower Urinary T ract 
Disease.
• Lower Urinary T ract Infection, Bacterial.
• Lower Urinary T ract Infection, Fungal.
• Urinary Retention, Functional.
• Vesicourachal Diverticula.
• UTI = urinary tract infection.
of John M. Kruger and Carl A. Osborne(continued)  Dysuria, Pollakiuria, and Stranguria

432  Blackwell’s Five-Minute Veterinary Consult  
EEar Mites
  BASICS
OVERVIEW
Otodectes cynotis  mites infest primarily the 
external ear canal and cause variable degrees 
of otic discharge and pruritus.
• Common in young dogs and cats, although 
it may occur at any age.
SIGNS
• Pruritus is usually present, but can be minimal.
• Pruritus primarily located around the ears, 
head, and neck; occasionally generalized.
• Thick, red-brown, or black otic exudate 
(“coffee grounds” appearance)—usually seen 
in the outer ear.
• Otic exudate and pruritus demonstrate 
individual variability.
• Crusting and scales may occur on the neck, 
rump, and tail (dogs).
• Excoriations on the convex surface of the 
pinnae often occur, owing to the intense 
pruritus.
Otodectes cynotis .
  DIAGNOSIS
• Pelodera  dermatitis.
• Notoedric mange.
• Chiggers.
• Otitis externa secondary to allergy/
• Flea bite hypersensitivity.
Normal
N/A
• Ear swabs placed in mineral oil—usually 
effective means of identification.
• Skin scrapings—may identify mites if signs 
are generalized.
• Mites may be visualized in external ear canal.
• Diagnosis may be made by response to 
  TREATMENT
• Outpatient.• Diet and activity—no alteration necessary.
• Very contagious—all animals in contact 
with the affected animal must be treated.
• Thoroughly clean and treat the environ- 
ment.
• Ears should be thoroughly cleaned with a 
commercial ear cleaner.
• Otic parasiticides should be used for 
7–10 days to eradicate mites and eggs; 
effective topical commercial products 
contain pyrethrins, thiabendazole, 
ivermectin, and milbemycin; treat during 
alternative weeks for two to three treatment 
cycles recommended to prevent reinfesta -
tion from eggs.
• Selamectin—per label instructions or 
repeated at 2 weeks.
• Imidacloprid/moxidectin (Advantage 
Multi/Advocate)—per label instructions.
• Ivermectin—200–300  μg/kg PO (three 
treatments) or SC (two treatments) at 14-day 
intervals; non-FDA-approved usage.
• Isoxazolines—per label instructions; 
non-FDA-approved usage.
• Flea treatments should be applied to animal 
for elimination of ectopic mites.
• Mites may persist in the environment; 
environmental treatment may be helpful.
• Ivermectin and moxidectin—sensitivity in 
ABCB-1 mutant dogs; do not use orally or by 
injection in collies, shelties, their crosses, or 
other herding breeds; use only if absolutely 
necessary in animals <6 months of age; an 
increasing number of toxic reactions have 
been reported in kittens.
• Ivermectin and milbemycin—cause elevated 
levels of monoamine neurotransmitter 
metabolites, which could result in adverse 
drug interactions with amitraz and benzo  - 
diazepines.
• Isoxazolines—use with caution in pets with 
previous history of seizures.
  FOLLOW-UP
• Ear swab and physical examination should 
be done 1 month after therapy commences.
• Prognosis is good.
• If signs persist after treatment, an addi-
tional, underlying cause may be present.
• Repeat infestation indicates an uncontrolled 
source of mites.  MISCELLANEOUS
T ransient papular dermatitis in human 
beings.
2018.
Thomas RC. T reatment of ectoparasites. In: 
Bonagura JD, T wedt DC, eds. Current 
Veterinary Therapy XV. St. Louis, MO: 
Elsevier Saunders, 2014, pp. 428–432.
Resnick

Canine and Feline, Seventh Edition  433
EEclampsia
  BASICS
OVERVIEW
• Postparturient hypocalcemia.
• Usually develops 1–4 weeks postpartum; 
may occur at term, prepartum, or during late 
lactation.
• Hypocalcemia alters cell membrane 
potentials, causing spontaneous discharge of 
nerve fibers and tonic–clonic contraction of 
skeletal muscles.
• Life-threatening tetany and convulsions, 
leading to hyperthermia.
• Cerebral edema possible.
• Dog—postpartum bitch; most common in 
toy breeds; higher incidence with first litter.
• Most common prior to day 40 postpartum; 
occasionally occurs prepartum.
• Breeds at increased risk—chihuahua, 
miniature pinscher, shih tzu, miniature 
poodle, Xoloitzcuintli, Pomeranian.
• Cat—rare.
SIGNS
• Poor mothering.
• Restlessness, nervousness.
• Panting, whining.
• Vomiting, diarrhea.
• Ataxia, stiff gait, limb pain.
• Facial pruritis.
• Muscle tremors, tetany, convulsions.
• Recumbency, extensor rigidity—usually 
seen 8–12 hours after onset of signs.
• Rapid respiratory rate.
• Dilated pupils, sluggish pupillary light 
responses.
• Muscle tremors, muscular rigidity, 
convulsions.
• Calcium supplementation during gestation, 
including dairy products.
• Inappropriate Ca : P ratio in gestational 
diet.
• Low bodyweight : litter size ratio.
• Poor prenatal nutrition.
• First litter.
• Large litter size.
  DIAGNOSIS
• Hypoglycemia—may be concurrent; hypo  - 
glycemia alone does not cause muscular 
rigidity.• Toxicosis—distinguished by signalment and 
history.
• Epilepsy or other neurologic disorder—
differentiated by signalment; calcium 
concentration diagnostic.
• Total serum calcium <9 mg/dL in bitches; 
<8 mg/dL in queens.
• Although ionized calcium ( <2.4–3.2 mg/dL) 
is the form important for normal neuro -
muscular function, measurement of total 
serum calcium is usually sufficient for 
• Hypoglycemia—may be concurrent.
• Hypomagnesemia has been reported in 
44% of affected bitches; may promote tetany.
• Serum potassium elevated in 56% of cases, 
due to metabolic acidosis or respiratory 
N/A
IMAGING
N/A
ECG may show prolonged QT interval, 
bradycardia, tachycardia, or ventricular 
premature complexes.
  TREATMENT
• Emergency inpatient.
• Hyperthermia—cool by wetting haircoat 
and exposing to breeze from fan.
• Puppies—remove from dam onto a foster 
dam or hand-raise; if not possible or 
undesirable due to behavioral need for 
contact with dam, remove pups from dam for 
24 hours, or until serum calcium is stabilized, 
and provide supplemental calcium for 
remainder of lactation; continue to monitor 
serum calcium level.
• Calcium gluconate—10% solution 
0.22–0.44 mL/kg IV given slowly to effect 
over 5 min; monitor heart rate or ECG 
during administration; corresponds to dosage 
of 50–150 mg/kg.
• Correct hypoglycemia—50% dextrose: 
0.5 g/kg diluted 1 : 3 with saline IV; can 
supplement maintenance IV fluids to 2.5% 
or 5% dextrose for longer-term treatment.
• Diazepam—0.5 mg/kg IV; for unresponsive 
seizures.
• Cerebral edema—if present, can treat with 
mannitol: 0.25–0.5 g/kg IV over 20 min, or 7.2% hypertonic saline 1–3 mL/kg IV over 
15–20 min.
• Long-term therapy—calcium carbonate or 
calcium gluconate 10–30 mg/kg PO q8h 
until lactation ends (calcium carbonate 
500 mg tablets supply 200 mg calcium).
• Magnesium supplementation may be 
helpful in hypomagnesemic bitches.
• Start puppies/kittens on solid food at 3–4 
Corticosteroids—avoid; cause decreased 
intestinal absorption and increased renal 
excretion of calcium.
  FOLLOW-UP
• Serum calcium concentration—monitor 
until stabilized in the normal range.
• Avoid calcium supplementation during 
• Diet—maternal: ensure calcium : phosphorus 
ratio of 1.1 : 1 or 1.2 : 1; avoid high-phytate 
foods (e.g., soybeans); puppies: supplement 
feeding for large litters.
• Death.
• Hand-raising of puppies.
• Probably will recur with subsequent litters; 
calcium supplementation can be started after 
parturition for bitches with history of 
eclampsia in prior litters.
• Prognosis—good with immediate treatment; 
poor with delayed treatment.
Davidson AP . Reproductive causes of 
hypocalcemia. Topics Compan Anim Med 
2012, 27:165–166.
Drobatz KJ, Casey KK. Eclampsia in dogs: 
31 cases (1995–1998). J Am Vet Med Assoc 
2000, 217(2):216–219.
Gonzalez, K. Periparturient diseases in the 
dam. Vet Clin North Am Small Anim Pract 
2018, 48(4):663–681.
Author  Joni L. Freshman

434  Blackwell’s Five-Minute Veterinary Consult  
EEctopic Ureter
  BASICS
OVERVIEW
• Congenital ureteral orifice(s) is inapprop­
riately positioned caudal to the bladder 
trigone (i.e., trigone, urethra, vagina, 
vestibule, uterus, or prostate), resulting in 
• A common cause of urinary incontinence in 
juvenile female dogs. Also seen in adult dogs.
• Dogs— >95% tunnel intramurally, 
traversing the urethra in the submucosa.
• Male dogs—commonly associated with 
severe hydronephrosis and hydroureter due to 
ureteral opening stenosis.
• Commonly associated with multiple anomalies 
of the urinary tract—including concurrent 
urethral sphincter mechanism incompetence 
(USMI), hydroureter, hydronephrosis, short 
urethra/intrapelvic bladder.
• Juvenile incontinent dogs.
• Infrequently reported in cats and male 
dogs; 20 : 1 ratio of female : male dogs.
• Dog breeds may be predisposed—retrievers, 
Siberian huskies, Newfoundlands, poodles, 
terriers.
SIGNS
• Constant or intermittent incontinence since 
birth.
• Normal voiding in some.
• Chronic urinary tract infection(s) (UTIs).
• May be asymptomatic (male dogs) and can 
have moderate to severe hydroureter/hydro  ­ 
nephrosis.
  DIAGNOSIS
• USMI.
• Inappropriate urination—urge incontinence, 
“overactive bladder,” behavioral (conscious 
urination).
• UTI—pollakiuria and urge incontinence.
• Vaginal pooling.
• Congenital hydroureter/hydronephrosis—
male dogs with ectopic ureter(s) (EUs) often 
continent.
• Short urethra/intrapelvic bladder syndrome.
Labwork is typically normal, except when 
patients have concurrent anomalies (e.g., 
renal dysplasia, pyelonephritis).
Urine bacterial culture and sensitivity—via 
cystocentesis.
IMAGING
• Cystoscopy (96% sensitivity).• CT (91% sensitivity).
• Urinary tract ultrasonography (60–91% 
sensitivity) can provide accurate diagnosis and 
anatomic information of the upper urinary 
tract. Color ­flow Doppler ultrasonography 
can provide location of ureteral jets, but does 
not guarantee the absence of a multifene­
strated ureter.
• Excretory urography (50–75% sensitivity) 
with positive contrast cystogram or a 
pneumocystogram.
• Retrograde urethrography (47% 
sensitivity).
Cystoscopy—definitive diagnosis and 
characterization of EU, short urethra 
syndrome, location of ectopic orifice in the 
genitourinary tract. Also allows for simultane­
ous treatment.
  TREATMENT
• Cystoscopic ­guided laser ablation (CLA)—
performed for intramural EU only. Opens 
ureteral tract in a minimally invasive manner; 
addresses concurrent vaginal defects, which 
may lead to considerable deviation of the 
urethra. Patients treated with CLA typically 
discharged the same day.
• Surgical—treatment of choice for extra­
mural EU: neoureterostomy, reimplantation, 
or rarely ureteronephrectomy; complication 
rates range between 14% and 25% including 
ureteral strictures, leakage, and infection.
• Use if incontinence persists after surgery.
• Phenylpropanolamine (1–1.5 mg/kg PO 
q8h) will improve continence after surgery/
laser therapy in 10–20% of dogs, improving 
continence levels to 50–60%.
• Testosterone propionate (2.2 mg/kg IM 
q2–3 days) or methyltestosterone (0.5 mg/kg/
day) is administered to male dogs. For longer 
action, testosterone cypionate (2.2 mg/kg IM 
q30 days) can be used; this approach is not 
advised in immature or intact males.
• Estriol (2 mg once daily per dog for 14 
days, followed by the lowest effective daily 
dose tapered every 7 days).
Other
T reatment for persistent incontinence after 
surgery/laser ablation—transurethral 
submucosal bulking agent injections: can 
improve continence to ~60–65%; placement 
of an artificial urethral sphincter (called a 
hydraulic occluder) can improve continence 
to ~80–90%.  FOLLOW-UP
• Warn owners that incontinence may 
continue in some patients after surgery. Many 
patients become continent with the addition 
of medications, collagen bulking, and/or 
placement of a hydraulic occlude.
• Dogs—continence with surgery (25–50%) 
or laser ablation (40–55%) alone, which 
improves to 60% with medications, 65% 
with bulking agent injection, and ~80–90% 
with placement of a hydraulic occlude.
• Hydronephrosis.
• Hydroureter.
• Ureterocele.
• Pelvic bladder.
• Persistent paramesonephric remnant.
• Vaginal septum.
• Renal dysplasia.
• Renal agenesis.
• USMI.
• Short urethra/intrapelvic bladder.
SEE ALSO
• Incontinence, Urinary.
• Pelvic Bladder.
• CLA = cystoscopic ­guided laser ablation.
• EU = ectopic ureter.
• USMI = urethral sphincter mechanism 
incompetence.
of Allyson C. Berent.

Canine and Feline, Seventh Edition  435
E
Ectropion
  BASICS
OVERVIEW
• Eversion or rolling out of the eyelid margin, 
resulting in exposure of the palpebral 
conjunctiva.
• Can be conformational/congenital 
(primary) or acquired (secondary).
• Exposure and poor tear retention/
distribution may predispose patient to 
irritation, recurrent infections, and sight-
threatening corneal disease.
• Dogs, seldom cats.
• Breeds with higher than average prevalence—  
sporting breeds (e.g., spaniels, hounds, and 
retrievers); giant breeds (e.g., Saint Bernard, 
mastiff); any breed with loose facial skin 
(especially bloodhounds).
• Primary—genetic predisposition in listed 
breeds; may occur in dogs <1 year old.
• Acquired—noted in other breeds; occurs 
late in life secondary to age-related loss of 
facial muscle tone and skin laxity.
• Intermittent—caused by fatigue; may be 
observed after strenuous exercise or when 
drowsy.
SIGNS
• Eversion of the lower eyelid with lack of 
contact of the lower lid to the globe and 
exposure of the palpebral conjunctiva and 
third eyelid.
◦ Often excessively long palpebral fissure 
(macroblepharon).
◦ Conjunctivitis and history of mucoid to 
mucopurulent discharge caused by chronic 
exposure to air and debris. Debris generally 
located between lid and globe in inferior 
conjunctival cul-de-sac.
◦ Tear staining of periocular skin caused by 
poor tear drainage.
• History of bacterial conjunctivitis.
• Primary disease—most common due to 
breed-associated facial conformation and 
alterations in eyelid support.
• Acquired disease—from marked weight loss 
or muscle mass loss about the head and 
orbits, tragic facial expression in hypothyroid 
dogs, and cicatricial ectropion from scarring 
of the eyelids secondary to injury or from 
surgical overcorrection of entropion.
  DIAGNOSIS
• Usually clinically obvious.
• Look for any underlying disorder in 
nonpredisposed breeds and dogs with late-age 
onset.• Loss of orbital or periorbital mass—may 
occur in patients with masticatory myositis.
• Facial nerve paralysis—associated with lack 
of muscle tone of orbicularis oculi muscles.
N/A
• Possible masticatory myositis—test for 
auto-antibodies against type 2M muscle fibers.
• Palpebral nerve paralysis or tragic facial 
expression—consider testing for hypo- 
IMAGING
N/A
• Palpebral nerve paralysis—full neurologic 
evaluation; potential for hypothyroidism.
• Secondary conjunctivitis—flush fornix and 
examine for follicles.
• Fluorescein or rose Bengal staining of 
cornea and conjunctiva—to identify corneal 
ulcerations; may reveal severity of exposure 
problem.
  TREATMENT
• Supportive care (topical lubricant, rinsing 
eyes with eyewash after being outside to 
remove debris) and good ocular and facial 
hygiene—sufficient for most mild disease.
• Surgical treatment—eyelid shortening or 
radical facelift; necessary for severely affected 
patients that have chronic ocular irritation.
• Intermittent, fatigue-induced condition—
do not treat surgically.
• Topical broad-spectrum ophthalmic 
antibiotics—bacterial conjunctivitis or 
corneal ulceration. Neomycin/polymyxin B/
bacitracin (or based on culture and 
sensitivity) q6–8h.
• Lubricant ointments (e.g., Puralube®)—
reduce conjunctival and corneal desiccation 
secondary to exposure.
• Hypothyroid and masticatory myositis-
induced conditions—may respond well to 
appropriate medical treatment of underlying 
disease.
N/A
  FOLLOW-UP
• May become more severe as patient ages.• Nonsurgically treated patient—monitor for 
signs of infectious conjunctivitis, exposure 
keratopathy, corneal ulceration, and facial 
• Masticatory myositis, extraocular myositis.
Old animals more likely to have ectropion 
secondary to loss of facial muscle tone.
SEE ALSO
• Myopathy – Masticatory  and Extraocular 
Myositis.
Stades FC, van der Woerdt A. Diseases and 
surgery of the canine eyelid. In: Gelatt KN, 
Ophthalmology, 5th ed. Ames, IA: 
Wiley-Blackwell, 2013, pp. 853–864.
Author  Sarah L. Czerwinski
editor acknowledge the prior contribution 
of J. Phillip Pickett.

436  Blackwell’s Five-Minute Veterinary Consult  
EEhrlichiosis and Anaplasmosis
  BASICS
Caused by Ehrlichia  and Anaplasma —tick-
borne rickettsial disease.
Dogs
• Obligate intracellular pathogens in three 
genera: Ehrlichia , Anaplasma , and 
Neorickettsia . • Ehrlichia —predominant 
species: E. canis : canine monocytic 
ehrlichiosis (CME); E. ewingii : granulocytic 
ehrlichiosis; E. chaffeensis : primarily human 
pathogen, may cause canine disease. 
• Anaplasma —A. phagocytophilum : 
granulocytic anaplasmosis; A. platys : 
thrombocytic anaplasmosis. •  Neorickettsia —
infect mononuclear cells (monocytes and 
macrophages): N. risticii : Potomac horse 
fever; rarely infects dogs; acquired by 
ingesting infected vectors; serum from 
infected dogs does not cross-react with 
Ehrlichia ; N. helminthoeca : salmon poisoning, 
primarily northwestern United States.
Cats
Feline ehrlichiosis (rare)—serologic, PCR, 
and cytologic evidence for Ehrlichia  (E. canis , 
E. canis- like, E. chaffeensis , E. ewingii ) and 
Anaplasma  (A. phagocytophilum ); clinical signs 
may include fever, lethargy, joint pain, 
anemia, hyperglobulinemia, and thrombo -
cytopenia; may also be asymptomatic.
• Anaplasma  and Ehrlichia  transmitted via 
tick bite; transmission time between 3h 
(E. canis ) and 18h; can occur via blood 
transfusion. •  E. canis—Rhipicephalus 
sanguineus  tick vector; infects mononuclear 
cells; 1–3-week incubation period; three 
stages of canine disease: ◦ Acute (2–4 
weeks)—spread to spleen, liver, lymph nodes; 
causes endothelial cell and perivascular 
inflammation, thrombocytopenia (possible 
antiplatelet antibodies), mild anemia; 
infections may be subclinical. ◦ Subclinical 
(months–years)—organism persists; hyper  - 
globulinemia; mild thrombocytopenia; dogs 
may eliminate infection, others remain 
persistently infected or develop chronic 
disease. ◦ Chronic—myelosuppression; 
pancytopenia. •  E. ewingii—Amblyomma 
americanum  tick vector; infects granulocytes; 
dogs can be persistently infected and 
asymptomatic; acute clinical signs include 
fever, neutrophilic polyarthritis, neutrophilia, 
reactive lymphocytes, and proteinuria; 
bleeding disorders uncommon.  
• A. phagocytophilum—Ixodes  spp. tick 
vector; infects granulocytes; infections can 
be asymptomatic and self-limiting; acute 
clinical signs include fever, lameness, thrombo  - 
cytopenia, and lymphopenia. •  A. platys—
tick vector likely R. sanguineus ; infects platelets; persistent or cyclic thrombo- 
• Multisystemic disease. •  Vasculature—
bleeding tendencies (thrombocytopenia and 
vascular inflammation). •  Hemic/lymphatic/
immune—bone marrow, spleen, lymph 
nodes. •  Nervous (meningitis, cerebral 
hemorrhage). •  Ophthalmic (anterior 
uveitis). •  Joint (neutrophilic arthritis).
PREVALENCE/GEOGRAPHIC 
DISTRIBUTION
• E. canis —year round, worldwide; higher 
prevalence in warm climates. •  E. ewingii —
warmer months; seroprevalence eastern 
and midwest United States.  
• A. phagocytophilum —warmer months; 
eastern, upper midwest, and Pacific coast 
United States.
Species
Dogs and cats (infrequent).
Chronic CME—German shepherd dogs, 
Belgian Malinois.
• Average age 5.2 years. •  Range 2 months–14 
years.
SIGNS
Vary in severity and duration, dependent on 
host, coinfections, and strain variations.
• Fever, lethargy, anorexia, weight loss. 
• Spontaneous bleeding—sneezing, epistaxis, 
petechia, ecchymosis. •  Ocular discharge/
pain. •  Lameness. •  Ataxia, head tilt
Acute
• Bleeding diathesis. •  Fever. •  Generalized 
lymphadenopathy. •  Organomegaly (spleen, 
liver). •  Ocular discharge. •  Lameness. •  Ticks.
Chronic E. canis
• Pale mucous membranes (anemia). 
• Ulcerative stomatitis. •  Hind limb or 
scrotal edema. •  Uveitis, hyphema, retinal 
hemorrhages. •  Ataxia, vestibular dysfunction, 
Coinfection with other vector-borne diseases 
(VBDs).
  DIAGNOSIS
• Rocky Mountain spotted fever ( Rickettsia 
rickettsii )—seasonal (Mar–Oct); diagnose 
with serology; same treatment. •  Immune-mediated thrombocytopenia—no fever or 
lymphadenopathy; rule out VBD. •  Systemic 
lupus erythematosus—positive antinuclear 
antibody (ANA) test. •  Multiple myeloma—
monoclonal gammopathy, bony lesions. 
• Chronic lymphocytic leukemia—bone 
marrow cytology; PCR for antigen receptor 
rearrangements (PARR; E. canis  infrequently 
PARR negative). •  Brucellosis.
Acute
• Thrombocytopenia, anemia, leukopenia 
(lymphopenia, neutropenia, and eosino -
penia), or leukocytosis (granular 
lymphocytosis, monocytosis). •  Morulae—
intracytoplasmic inclusions in leukocytes, 
rare. •  Hyperglobulinemia—progressive 
increase 1–3 weeks postinfection. •  Hypoalbu  - 
minemia. •  Mild increases in liver enzyme 
activities, azotemia, hyperbilirubinemia. 
Chronic
• Pancytopenia—anemia, thrombocytopenia, 
neutropenia, but monocytosis and lympho -
cytosis possible. •  Hyperglobulinemia—  
magnitude correlates with duration of 
infection; usually polyclonal gammopathy, 
occasionally monoclonal. •  Hypoalbuminemia. 
• Antibodies present ~3 weeks postinfection. 
• Immunofluorescent antibody test (IFAT)—
sensitive; cross-reactivity between Ehrlichia  
species; use same laboratory to compare acute 
and convalescent titers; fourfold increase 
paired in convalescent titer indicates active 
infection; detection at one time-point may 
represent past exposure or active infection. 
• Rapid point-of-care (POC) screening 
test—sensitivity and specificity vary 
depending on test; overtly healthy dogs with 
positive POC tests should have CBC, 
Biochemistry, UA, PCR or paired IFAT to 
identify evidence of infection before 
treatment; animals can remain seropositive by 
POC for years, even after infection cleared.
PCR Testing
• Detects pathogen DNA; sensitive indicator 
of active or recent infection. •  Whole blood 
or tissue (spleen, lymph node, liver, bone 
marrow); identifies species; detect as early as 
7 days postinfection. •  Negative PCR result 
cannot rule out VBD infections; false 
negative can occur due to low organism load; 
genetic variations can prevent PCR detection. 
• Combining serology and PCR optimal for 
accurate diagnosis.
Additional Tests
• Coombs’ positive anemia; indicates 
concurrent immune-mediated erythrocyte 
destruction; may be positive in dogs with 
babesiosis, other VBD. •  Test for VBD

Canine and Feline, Seventh Edition  437
Ecoinfections. •  Culture and sensitivity 
testing (blood, urine) indicated in febrile 
patients.
Bone Marrow Aspirate
• Acute—hypercellularity of megakaryocytic 
and myeloid series. •  Chronic—erythroid 
hypoplasia with increased M : E ratio, 
plasmacytosis. •  Increased number of mast 
cells.
• Acute—serosal and mucosal petechiae; 
lymphadenopathy, splenomegaly, 
hepatomegaly, and red bone marrow; 
perivascular infiltrates of macrophages and 
lymphocytes (lung); periportal infiltrates of 
lymphocytes and macrophages (liver); 
lymphoid hyperplasia (spleen). •  Chronic—
pale marrow, subcutaneous edema; 
histologically, perivascular plasma cell 
infiltrates in organs; multifocal nonsuppurative 
meningoencephalitis with lymphoplasmacytic 
infiltrate.
  TREATMENT
• Inpatient—medical stabilization for acute 
signs. •  Outpatient—stable patients; frequent 
monitoring for therapeutic response.
• Balanced electrolyte solution IV. •  Blood or 
platelet-rich plasma transfusion for severe 
anemia or thrombocytopenia.
• Acute—prognosis excellent with appropriate 
therapy. •  Chronic—prognosis guarded; 
cytopenia resolution may take >6 months; 
prognosis poor if hypoplastic bone marrow.
• Progression to chronic prevented by early 
effective treatment; serological tests may stay 
positive (IFAT ≤1 year and POC for years); 
reinfection can occur if animals reexposed. 
• Breed risks for chronic CME.
• Doxycycline—5 mg/kg PO q12h or  
10 mg/kg PO q24h for 3–4 weeks; clinical 
response usually in 1–2 days; slower response 
in chronic ehrlichiosis or neurologic disease. • Prednisolone or prednisone, use with 
antibiotics; anti-inflammatory (0.5–1 mg/kg 
PO q12–24h for 3–5 days) for polyarthritis; 
immunosuppressive (1–2 mg/kg PO q12h for 
5 days; rarely exceed 60 mg/dog/day) when 
immune-mediated disease suspected. •  For 
CME, prophylactic antibiotics if neutrophils 
<1000 cells/ μl for >1 week.
• Glucocorticoids in myelosuppressive CME. 
• Glucocorticoids in animals with diabetes 
mellitus, gastrointestinal ulceration, 
concurrent or recent nonsteroidal anti-
inflammatory drug (NSAID) use.
• Prolonged immunosuppressive cortico -
steroid use may interfere with elimination of 
E. canis . • Doxycycline in dogs with liver 
disease or abnormal liver enzyme values.
• Minocycline—10 mg/kg PO q12h for 3–4 
weeks. •  Rifampicin: 10 mg/kg PO q24h for 
3 weeks (do not exceed 10 mg/kg/day in 
dogs); less effective.
  FOLLOW-UP
• CBC, blood smear examination—2, 4, 8 
weeks after starting antibiotics; recurrence 
of clinical signs post treatment suggests 
treatment failure, reinfection, or concurrent 
infection with pathogen partially sensitive 
to therapy ( Babesia , Bartonella ). • IFAT—9 
months post treatment; most dogs become 
seronegative; extended seropositivity 
may indicate reinfection or ineffective 
treatment. •  PCR—1–2 months post 
treatment for evidence of pathogen 
clearance; if PCR positive, repeat anti -
biotics for 4–6 weeks, ensure use of 
acaricides; if persistently negative, change 
drug. •  POC assay—not used to monitor 
treatment response.
• Control tick infestation—acaricides: topical 
(spot treatments and collars)—imidacloprid/
flumethrin, fipronil, permethrin, deltamethrin, 
and amitraz (do not use permethrin, delta -
methrin, or amitraz on cats); systemic—
isoxazolines. •  Manually remove ticks; use 
gloves; ensure removal of mouth parts.EXPECTED COURSE AND PROGNOSIS
• Acute—excellent prognosis with 
appropriate treatment; most immuno -
competent dogs recover, enter subclinical 
phase, or clear infection; treatment accelerates 
recovery, may prevent chronic phase. 
• Chronic—may take 4 weeks for clinical 
response, 6 months for cytopenia rebound; 
prognosis poor and expensive medical 
management with hypoplastic marrow. 
• Ehrlichia  and Anaplasma  antibodies do not 
protect against reinfection.
• Babesia . • Bartonella . • Hemotropic 
Mycoplasma . • Leishmania.
E. canis , E. ewingii , E. chaffeensis ,  
A. phagocytophilum , and A. platys  can infect 
humans via tick bite; R. sanguineus  prefers 
dogs, will bite humans in living conditions 
with high vector population; A. americanum  
bites humans; Ixodes  bite humans and 
transmit Borrelia burgdorferi , Babesia microti , 
likely E. muris .
SYNONYMS
• Canine hemorrhagic fever. •  Canine 
rickettsiosis. •  Canine typhus. •  T racker dog 
disease. •  T ropical canine pancytopenia.
• ANA = antinuclear antibody. •  CME = 
canine monocytic ehrlichiosis. •  IFAT = 
indirect fluorescent antibody test. •  NSAID = 
nonsteroidal anti-inflammatory drug. 
• PARR = PCR for antigen receptor 
rearrangements. •  POC = point of care. 
• VBD = vector-borne disease.
Mylonakis ME, Harrus S, Breitschwerdt EB. 
An update on the treatment of canine 
monocytic ehrlichiosis (Ehrlichia canis). Vet 
J 2019, 246:45–53.
Author  Barbara Qurollo
available online(continued)  Ehrlichiosis and Anaplasmosis

E438  Blackwell’s Five-Minute Veterinary Consult  
EElbow Dysplasia
  BASICS
A group of developmental abnormalities that 
lead to malformation, degeneration, and 
secondary osteoarthritis of the elbow joint.
• Four abnormalities—un-united anconeal 
process (UAP), osteochondritis dissecans 
(OCD), fragmented medial coronoid process 
(FMCP), and incongruity; alone or in 
combination; may be seen in one or both 
elbows; bilateral disease common (50% of cases).
• Terminology— medial compartment disease 
(MCompD) involves any pathology within 
the medial compartment, while medial 
coronoid process disease (MCD) is used to 
describe all pathologies of the medial coronoid 
process such as fissuring, fragmenting, 
sclerosis, microfracture, and cartilage damage.
• FMCP and incongruity are the most 
common documented MCompD pathologies.
• UAP—delayed closure of growth plate 
between anconeal process and proximal ulnar 
metaphysis (olecranon) by 5 months of age; 
may be result of abnormal mechanical stress 
on anconeal process.
• OCD—affects medial aspect of humeral 
condyle; disturbance in endochondral 
ossification causes retention of articular 
cartilage and subsequent mechanical stress 
leads to cartilage flap lesion.
• FMCP—chondral or osteochondral 
fragmentation or fissure of medial coronoid 
process of ulna; possibly manifestation of 
osteochondrosis of coronoid process; 
coronoid does not have separate ossification 
center; may be result of abnormal mechanical 
stress on medial coronoid process considered 
to be due to incongruity.
• Incongruity—asynchronous growth 
between radius and ulna may lead to 
abnormal loading, wearing, and erosion of 
cartilage in humeroulnar compartment. 
Malformation of trochlear notch of ulna; 
elliptical trochlear notch with decreased arc of 
curvature is too small to articulate with 
humeral trochlea—resulting in major points 
of contact at anconeal process, coronoid 
process, and medial humeral condyle.
GENETICS
High heritability
• Most common cause for elbow pain and 
lameness.
• One of the most common causes for 
thoracic lameness in large-breed dogs.
Species
Dog
Large and giant breeds—Labrador retrievers; 
Rottweilers; golden retrievers; German 
shepherds; Bernese mountain dogs; chow 
chows; bearded collies; Newfoundlands.
• Age at onset of clinical signs—typically 
4–10 months.
• Age at diagnosis—generally 4–18 months.
• Onset of symptoms related to degenerative 
joint disease (DJD)—any age.
• FMCP—males predisposed.
• UAP , OCD, incongruity—none established.
SIGNS
• Lameness—if no distinct abnormalities noted 
on physical examination or radiographs, early 
intervention may demand advanced imaging.
• Any resistance at all in flexion in immature 
dog should raise suspicion of elbow dysplasia.
• Not all patients are symptomatic when young.
• Intermittent episodes of elbow lameness 
due to advanced DJD changes in mature 
patient—common.
Intermittent or persistent thoracic limb 
lameness—exacerbated by exercise; progressed 
from stiffness seen only after rest.
• Pain—elicited on elbow hyperflexion or 
extension; elicited when holding elbow and 
carpus at 90° while pronating and supinating 
carpus and applying pressure to medial 
compartment.
• Affected limb—tendency to be held in 
abduction and supination.
• Joint effusion and capsular distension—
especially noted between lateral epicondyle 
and olecranon.
• Crepitus—may be palpated with advanced 
DJD.
• Diminished range of motion.
CAUSES
• Genetic.
• Developmental.
• Nutritional.
• Rapid growth and weight gain.
• High-calorie diet.
  DIAGNOSIS
• T rauma.
• Septic arthritis.• Panosteitis.
• Avulsion or calcification of flexor muscles.
• Synovial sarcoma.
N/A
IMAGING
• Image both elbows—high incidence of 
bilateral disease.
• UAP , OCD, FMCP , and incongruity—
elbow DJD recognized by osteophytes on 
cranial margin of radial head (37%), 
anconeal process (70%), and epicondyles 
(medial and lateral), and medial coronoid 
process; sclerosis of ulna caudal to coronoid 
process and trochlear notch; stairstep 
between joint surface of radius and lateral 
coronoid.
• UAP—best diagnosed from mediolateral 
hyperflexed view; may see lack of bony union. 
Comparison to contralateral elbow may be 
helpful, although high incidence of bilateral 
disease should be kept in mind.
• OCD—best diagnosed from craniocaudal 
and craniocaudal-lateromedial oblique views; 
reveals radiolucent defect or flattening of 
medial aspect of humeral condyle.
• FMCP—may not be visualized in some 
cases; diagnosis then presumptive based on 
DJD and lack of UAP or OCD lesions; 
commonly see trochlear sclerosis and/or early 
osteophyte formation on proximal caudal 
surface of anconeal process with FMCP .
Other
CT, MRI, and linear tomography—can 
provide more definitive evidence for fissures 
and nondisplaced fragments. CT is necessary 
in many cases of MCD as survey radiographs 
have low sensitivity.
• Joint tap and analysis of synovial fluid—
confirm involvement of joint.
• Synovial fluid—should be straw colored 
with normal to decreased viscosity; cytology 
reveals <5,000 nucleated cells/ μL (>90% are 
mononuclear cells); normal results do not 
necessarily rule out the diagnosis.
• Arthroscopy—may help diagnose UAP , 
MCD, OCD, and incongruity.
• UAP—fibrous union between anconeal 
process and proximal ulnar metaphysis; 
fibrous tissue invasion and degeneration of 
anconeal process; DJD.
• OCD—chondral flap on medial humeral 
condyle; sclerosis of underlying subchondral 
bone with fibrous tissue invasion; erosive 
lesion on apposing coronoid cartilage; DJD.
fragmentation of cranial tip or lateral margin 
of medial coronoid; erosive lesion on cartilage 
of apposing medial aspect of humeral 
condyle; DJD.

Canine and Feline, Seventh Edition  439
E
E• Incongruity—a step greater than 2 mm 
noted between medial border of radial head 
and lateral border of medial coronoid process.
• MCompD—erosive lesions involving part 
or all of medial coronoid process and 
apposing articular cartilage of medial aspect 
of humeral condyle; DJD; linear striations in 
articular cartilage.
  TREATMENT
Surgery—controversial but recommended for 
• Cold packing elbow joint—perform 
immediately post surgery to help decrease 
swelling and control pain; perform at least 
20 minutes q8h for 3–5 days.
• Passive range-of-motion exercises—benefi-
cial until patient can bear weight on limb(s), 
then progress into static and dynamic 
therapeutic exercises.
• If osteoarthritis is present, then multimodal 
management is necessary as for arthritic 
management of any joint.
ACTIVITY
• Restricted for all patients postoperatively.
• Consideration for avoidance of high 
concussive activities for life.
DIET
load and stress on affected joint(s).
• Restricted weight gain and growth in 
young dogs—may decrease incidence and 
severity.
• Discuss heritability of disease.
• Discuss likelihood of DJD progression 
regardless of intervention.
• Discuss influence of excessive intake of 
nutrients that promote rapid growth.
• Severity of DJD and advanced age of 
patient—negatively influence outcome. 
Generally DJD progresses faster without 
• UAP—four options: removal, lag screw 
fixation, dynamic proximal ulnar osteotomy, 
and lag screw fixation plus dynamic proximal 
osteotomy; base decision on degree of DJD, 
patient’s age, and surgical expertise.
• OCD and FMCP—medial approach to 
elbow (diagnostic differentiation not 
necessary); removal of loose fragment(s).
• Incongruity—controversial; four options: 
no surgery, subtotal coronoidectomy, 
dynamic proximal ulnar osteotomy, intra-
articular osteotomy; base decision on type of incongruity, degree of DJD, patient’s age, and 
surgical expertise.
• Arthroscopic diagnosis and treatment—excel -
lent option for FMCP , OCD, and incongruity; 
benefits: superior visualization, minimally 
invasive, superior to arthrotomy in outcome.
• None that promotes healing of osteochon-
dral or chondral fragments.
(NSAIDs)—minimize pain, decrease 
inflammation, symptomatically treat 
associated DJD.
• Deracoxib (3–4 mg/kg PO q24h, chewable).
• Carprofen (2.2 mg/kg PO q12h or q24h).
• Meloxicam (load 0.2 mg/kg PO, then 0.1 
mg/kg PO q24h—liquid).
• Tepoxalin (load 20 mg/kg, then 10 mg/kg 
PO q24h).
Avoid corticosteroids—potential side effects; 
articular cartilage damage associated with 
long-term use.
NSAIDs—gastrointestinal irritation may 
preclude use in some patients.
N/A
Chondroprotective drugs (e.g., polysulfated 
chondroitin sulfate)—may help limit cartilage 
damage and degeneration; may help alleviate 
pain and inflammation.
  FOLLOW-UP
• Post surgery—limit activity for minimum 
of 12 weeks; encourage early, active, 
controlled movement of affected joint(s); 
consider formal rehabilitation therapy.
• Yearly to twice-yearly examinations—
recommended to evaluate progression of DJD.
• Discourage breeding of affected animals.
• Do not repeat dam–sire breeding that 
resulted in affected offspring.
N/A
• Progression of DJD—expected.
• Prognosis—fair to good for all forms.  MISCELLANEOUS
N/A
N/A
N/A
N/A
SYNONYMS
Elbow osteochondrosis.
SEE ALSO
Osteochondrosis
process.
• MCD = medial coronoid process disease.
• MCompD = medial compartment disease.
drugs.
• OCD = osteochondritis dissecans.
• UAP = un-united anconeal process.
https://www.ofa.org/diseases/elbow-dysplasia
Cook CR, Cook JL. Diagnostic imaging of 
canine elbow dysplasia: a review. Vet Surg 
2009, 38(2):144–153.
Fitzpatrick N, Yeadon R. Working algorithm 
for treatment decision making for develop-
mental disease of the medial compartment 
of the elbow in dogs. Vet Surg 2009, 
38(2):285–300.
Sallander MH, Hedhammar A, T rogen ME. 
Diet, exercise, and weight as risk factors in 
hip dysplasia and elbow arthrosis in 
Labrador retrievers. J Nutr 2006, 136(7 
Suppl):2050S–2052S.
Samoy Y, Van Ryssen B, Gielen I, et al. 
Review of the literature: elbow incongruity 
in the dog. Vet Comp Orthop T raumatol 
2006, 19(1):1–8.
available online(continued)  Elbow Dysplasia

440  Blackwell’s Five-Minute Veterinary Consult  
EElectric Cord Injury
  BASICS
OVERVIEW
• Electric cord injury is an uncommon event 
that occurs when an animal bites an electric 
cord. •  Other causes of electrocution are 
uncommon in dogs and cats but can occur. 
• Household electrical currents are alternat-
ing (50–60 Hz), 110–120 or 220–240 volts 
depending on geographic location, and are 
dangerous. •  Injury can be caused due to 
thermal injury or due to disruption of normal 
electrophysiologic activity of excitable tissue. 
• Pulmonary edema can be a sequela to 
electrocution and the pathophysiology is 
thought to be neurogenic and centrally 
mediated, leading to pulmonary hyperten-
sion. •  Cataract formation is reported 
following electrocution.
• Most commonly dogs; also cats. •  Most 
commonly young animals; in published 
report age ranged from 5 months to 1.5 years. 
• No breed or sex predilections. •  No genetic 
basis.
SIGNS
• Burns associated with gingiva, tongue, 
palate. •  Singed hair or whiskers. •  Most 
common clinical signs are related to acute 
dyspnea. •  Coughing. •  Tachypnea. 
• Orthopnea. •  Increased respiratory effort. 
• Cyanosis. •  Crackles during pulmonary 
auscultation. •  Tachycardia. •  Muscle 
tremors. •  Tonic–clonic activity. •  Collapse.
• Chewing electric cord. •  Young animals.
  DIAGNOSIS
• Left-sided congestive heart failure due to 
congenital or acquired heart disease; the 
presence of cardiac murmur or dysrhythmia 
may help differentiate; however, dysrhythmias 
may be seen with electric cord injury. 
• Vitamin K antagonist, rodenticide 
intoxication history (pulmonary hemorrhage). 
• Thoracic trauma (pulmonary contusions)—  
history, thoracic radiographs. •  Other causes 
of noncardiogenic pulmonary edema. 
• Pleural space disease—muffled lung sounds 
during auscultation, thoracic radiographs. 
• Thermal or chemical injuries—history, 
physical examination, thoracic radiographs. 
• Exposure to fire and smoke inhalation—
history, physical examination. •  Atypical pneumonia—history, physical examination, 
thoracic radiographs.
May help rule out other systemic causes of 
noncardiogenic pulmonary edema.
Arterial blood gas analysis may be useful to 
document hypoxemia; this may be difficult to 
perform in unstable patients.
IMAGING
• Thoracic radiographs may help distinguish 
between cardiogenic and noncardiogenic 
causes of pulmonary edema. •  Radiographic 
pattern is usually a generalized, mixed alveolar 
bronchial pattern; edema is often most 
notable in caudal dorsal lung fields. 
• Pulmonary venous congestion is absent 
with noncardiogenic pulmonary edema. 
• Echocardiography may help identify or rule 
out underlying cardiac disease.
• ECG—may help distinguish cardiogenic 
disease from noncardiogenic disease; however, 
dysrhythmias may be seen with electrocution 
and other causes of noncardiogenic pulmo-
nary edema.
• Pink, frothy fluid in airways. •  Fluid-filled, 
congested lungs. •  Subendocardial and 
subepicardial petechiae. •  Circumscribed, 
pale gray or tan oral lesions.
  TREATMENT
• If patient is close to live wire, turn off 
electricity and/or remove patient to safe area. 
• Establish patent airway if patient is 
unconscious. •  Oxygen supplementation. 
• Mechanical ventilation may be required. 
• Establish venous access.
• If in shock—treat with intravenous crystalloids 
(90 mL/kg/h in dog, 45–60 mL/kg/h in cat) or 
colloids (20 mL/kg in dogs, 5–10 mL/kg in 
cats). •  If pulmonary edema is present—
furosemide 2–4 mg/kg IV; this is controversial 
as this is a form of noncardiogenic pulmonary 
edema. •  Anxiolytic therapy if dyspneic—
butorphanol 0.1–0.2 mg/kg IV. 
• Corticosteroids have been employed, but are 
controversial and of unknown value. •  Inotropic 
support if required. •  Antiarrhythmic therapy if required. •  Oral and cutaneous burns—treated 
symptomatically.
  FOLLOW-UP
• Patient should be monitored until stable. 
• Physical examination. •  Monitor oral 
lesion; may prevent patient from eating. 
• ECG. •  Central venous pressure. •  Blood 
pressure. •  Arterial blood gas. •  Thoracic 
• Damaged electric cords should be discarded. 
• Avoid animal exposure to electric cords. 
• Follow child safety rules for a safe home.
• Infected burn wounds can occur but are 
uncommon. •  Oronasal fistula due to severe 
burns.
• Prognosis based on response to therapy. 
• Pulmonary edema can develop as soon as 
1 hour and as late as 36 hours after incident. 
• Pulmonary edema associated with electro  - 
cution is associated with high mortality 
(38.5%). •  If patient survives first 24 hours, 
prognosis improves. •  Resolution of pulmonary 
edema may take 3–5 days. •  Most oral lesions 
resolve. •  Inappetence related to oral lesions 
resolves.
Cataracts have been reported in one dog 18 
months after electrocution.
Brightman AH, Brogdon JD, Helper LC, 
Everds N. Electrical cataracts in the canine: 
a case report. J Am Anim Hosp Assoc 1984, 
20:895–898.
Drobatz KJ, Saunders HM, Pugh CR, 
Hendricks JC. Noncardiogenic pulmonary 
edema in dogs and cats: 26 cases (1987–
1995). J Am Vet Med Assoc 1995, 
206:1732–1736.
Kolata RJ, Burrows CF . The clinical features 
of injury by chewing electrical cords in dogs 
and cats. J Am Anim Hosp Assoc 1981, 
17:219–222.

Canine and Feline, Seventh Edition  441
EEnamel Hypoplasia/Hypocalcification
  BASICS
OVERVIEW
• Enamel hypoplasia is the inadequate 
deposition of normal enamel matrix, affecting 
one or several teeth.
• The crowns can have areas of normal 
enamel next to hypoplastic or missing 
enamel.
• Apparent defect in enamel surfaces, often 
pitted and discolored; focal or generalized, 
due to disruption of normal enamel 
• Most cases are primarily aesthetic; some 
have extensive structural damage, even root 
involvement. The dentin is rarely exposed 
with hypoplasia.
• Enamel hypoplasia is less common than 
hypocalcification.
• Enamel hypocalcification refers to 
inadequate mineralization (calcification) of 
enamel, affecting several or all teeth. The 
crowns are covered by poorly formed, rough 
enamel that may easily be worn or flaked 
away and have light brown discoloration. 
There can be areas of normal enamel next to 
areas of abnormal enamel.
• Systemic influences during enamel 
formation (e.g., distemper, fever) over an 
extended time may cause generalized changes; 
local or focal influences (e.g., trauma, even 
from deciduous tooth extraction) over a short 
time may cause specific patterns or bands.
• Teeth may be more sensitive with exposed 
dentin, and occasionally fractures of severely 
compromised teeth occur; usually they 
remain fully functional.
• Dogs and less commonly cats.
• Often apparent at time of tooth eruption 
(after 6 months of age) or shortly thereafter 
(with signs of wear).
SIGNS
Discolored teeth.
• Irregular, pitted, or flaky enamel surface 
with discoloration of diseased enamel and 
potential exposure and staining of underlying 
dentin (light brown).
• Early or rapid accumulation of plaque and 
calculus on roughened tooth surface; possible 
gingivitis and/or accelerated periodontal disease.
• Teeth may fracture easily.
• Animals may show cold sensitivity 
(avoiding outdoor water or refrigerated food).
• Insult during enamel formation.
• Canine distemper virus, fever, trauma (e.g., 
accidents, fractured deciduous tooth, excessive 
force during deciduous tooth extraction).  DIAGNOSIS
• Enamel staining—discolored but smooth 
surface (tetracycline).
• Carious lesions—cavities with decay.
• Amelogenesis imperfecta—genetic and/or 
developmental formation and maturation 
abnormalities other than hypomineralization.
• Tooth resorption—similar to that found in 
cats, also found in dogs.
• Appropriate preanesthetic diagnostic when 
N/A
IMAGING
• Intraoral radiographs are necessary to 
determine the structure and viability of roots.
• Cases reported of abnormal root formation, 
no root formation, or separated crown and 
root.
None
  TREATMENT
• T reatment depends upon extent of lesions 
and equipment and materials available.
• Goal is to provide the smoothest surface 
possible.
• Enamel hypoplasia typically does not require 
treatment as the enamel is normal, just 
decreased in thickness. Enamel hypocalcification 
typically benefits from treatment.
Optimal Treatment
• Gently remove diseased enamel (enamel 
scrub) with white stone burs or finishing 
disks on high-speed handpiece (adequate 
water coolant).
• Take care not to damage the tooth—excess 
enamel/dentin removal; hyperthermic damage 
to pulp.
• Focal defects may be amenable to 
composite restoration; many restorative 
materials (bonding agents, composites) 
require use of light-curing units and 
appropriate skill levels.
• Bonding agent recommended to seal 
exposed dentinal tubules and protect surfaces.
• Extraction is recommended if the root is 
significantly malformed; extraction or root canal 
therapy if tooth is radiographically nonvital.
Alternative Treatment
• Soft, diseased enamel can sometimes be 
removed with ultrasonic scalers or hand 
instruments, but avoid excessive removal and 
hyperthermia.• Fluoride treatment can be used to decrease 
sensitivity and enhance enamel strength.
N/A
  FOLLOW-UP
Inform the owner that further degeneration 
of remaining enamel may occur, necessitating 
additional therapy in the future, or that 
affected teeth may become nonvital over 
time, requiring root canal therapy or 
• Regular professional dental cleaning and a 
routine homecare program (brushing); may 
include weekly application of stannous 
fluoride at home (minimize ingestion because 
of toxicity).
• Avoid chewing on hard objects.
https://avdc.org/avdc-nomenclature
Bittegeko SB, Arnbjerg J, Nkya R, Tevik A. 
Multiple dental developmental abnormalities 
following canine distemper infection. J Am 
Anim Hosp Assoc 1995, 31(1):42–45.

E442  Blackwell’s Five-Minute Veterinary Consult  
EEncephalitis
  BASICS
Inflammation of the brain with or without 
concurrent inflammation of the meninges 
and spinal cord.
• Immune-mediated mechanism, usually of 
unknown triggering factor. •  Infection of 
the brain.
• Nervous. •  Multisystemic signs—usually 
seen if infectious cause.
Unknown
• Immune-mediated—worldwide. 
• Infectious—varies depending on infectious 
agent distribution.
Species
Immune Mediated
• Meningoencephalitis of unknown origin 
(MUO) can happen in any breed. 
• Granulomatous meningoencephalitis 
(GME)—toy poodle and terrier. •  Necrotizing 
meningoencephalitis (NME)—pug and 
chihuahua. •  Necrotizing leukoencephalitis 
(NLE)—Yorkshire terrier and French bulldog. 
• Eosinophilic meningoencephalitis (EME)—
golden retriever and Rottweiler. •  Idiopathic 
tremor syndrome—West Highland white 
terrier, Maltese. •  Greyhound nonsuppurative 
meningoencephalitis—greyhound.
• Pyogranulomatous meningoencephalomy -
elitis—pointer dogs. •  Aspergillosis—German 
shepherd. •  Protothecosis—boxer, collie. 
• Cryptococcosis—American cocker spaniel.
Feline Infectious Peritonitis (FIP)
Burmese
• Peak 3–7 years old; can happen at any age 
in dogs older than 4 months old. •  GME—
peak 4–8 years old. •  NME and NLE—mean 
2.5 years old (6 months–7 years). •  Cats—
mean 9 years old.
T wo peaks: <2 years and >8 years.
MUO—females slightly predisposed.
SIGNS
• Immune mediated—acute to chronic onset 
and progression (days to months).
• Infectious—acute onset with rapid 
progression (days).Physical Examination Findings
• Immune mediated—none. •  Infectious—
fever, lethargy, diffuse pain, ocular lesions, 
coughing, diarrhea.
• Rostral fossa—seizures, blindness, abnormal 
mentation, absent menace and nasal septum 
stimulation responses, delayed postural 
reactions. •  Caudal fossa—lethargy, cranial 
nerve deficits, ataxia (proprioceptive, vestibular, 
and/or cerebellar), paresis. •  Progression (e.g., 
anisocoria, pinpoint pupils, decreasing level of 
consciousness, poor physiologic nystagmus)—
suggests increased intracranial pressure with 
potential brain herniation.
CAUSES
Dogs
• Idiopathic—MUO, GME, NME, NLE, 
EME, pyogranulomatous meningoencephalo-
myelitis, greyhound nonsuppurative menin -
goencephalitis, idiopathic tremor syndrome. 
• Postvaccinal—distemper, rabies. •  Viral—
distemper, rabies, pseudorabies, herpesvirus, 
parvovirus, coronarivus, parainfluenza, West 
Nile virus, eastern, western and Venezuelan 
equine encephalomyelitis virus, Bunyaviridae , 
Flaviviridae . • Rickettsial— Ehrlichia canis , 
Neorickettsia helminthoeca , Anaplasma phagocyt -
ophilum , Rocky mountain spotted fever. 
• Bacterial—aerobic, anaerobic, mycoplasma, 
mycobacterium. •  Fungal— Blastomyces , 
Histoplasma , Cryptococcus , Coccidioidomyces , 
Aspergillus , Phaeohyphomyces . • Protozoal—
Toxoplasma , Neospora . • Algal— Prototheca . 
• Parasitic—sarcocystis, encephalitozoon, larva 
migrans ( Dirofilaria , Toxocara , Ancylostoma , 
Cuterebra , Baylisascaris , Cysticercus ), 
trypanosoma.
Cats
• Viral—FIP , rabies, feline immunodeficiency 
virus (FIV), pseudorabies, paramyxovirus, 
Borna disease virus, West Nile virus, 
Bunyaviridae . • Bacterial—aerobic, anaerobic, 
mycoplasma, mycobacterium. •  Fungal—
Cryptococcus , Blastomyces , Histoplasma , 
Coccidioidomyces . • Protozoal— Toxoplasma . 
• Algal— Prototheca . • Parasitic—larva migrans 
(Dirofilaria , Toxocara , Ancylostoma , Cuterebra , 
Baylisascaris , Cysticercus ). • Idiopathic—
lymphohistiocytic meningoencephalomyelitis.
• Immunosuppressive drugs and FIV or 
feline leukemia virus (FeLV) infection—
infectious encephalitides. •  FIP: recent stress, 
multicat environment. •  Tick-infected 
areas—tick-borne rickettsial and viral 
infections. •  T ravel history—geographically 
localized infectious agents.
  DIAGNOSIS
• Cerebrovascular accident—should not 
progress after 24 hours. •  Congenital anomaly—primarily young animals. 
• T rauma—usually reported in history. 
• Metabolic encephalopathy—usually 
symmetric deficits, CBC/biochemistry 
abnormalities common. •  Toxic—usually 
acute. •  Neoplasia—signs may be similar; 
usually in older patients. •  Degenerative—
usually slow, progressive signs.
• Immune mediated—usually normal. 
• Infectious—CBC: leukocytosis if systemic 
signs; distemper: lymphopenia; FIP: 
lymphopenia, anemia; rickettsial disease: 
anemia, thrombocytopenia; fungal/parasitic: 
occasionally eosinophilia; biochemistry: FIP: 
hyperglobulinemia; distemper: hyper/
hypoglobulinemia; rickettsial disease: 
hyperglobulinemia; some fungal diseases: 
hypoalbuminemia, hyperglobulinemia, 
hypercalcemia; urinalysis: fungus rarely seen.
• Serology—in serum or cerebrospinal fluid 
(CSF); available for fungal, protozoal, rickettsial, 
and viral diseases; may not differentiate exposed/
vaccinated animals from active disease; 
antibodies appear 2–3 weeks after infection; 
immunoglobulin (Ig) M higher predictive 
positive value than IgG for Toxoplasma , 
preferred test for Neospora , low sensitivity/
specificity for FIP . •  Histology—postmortem; 
lacks specificity; may reveal specific inclusion 
bodies for viral infections (e.g., distemper, 
rabies). •  Immunohistochemistry—
postmortem; usually high sensitivity and 
specificity; best test to confirm FIP . •  PCR—
available for viral, fungal, rickettsial, protozoal 
diseases in blood and CSF; highly sensitive for 
distemper; low sensitivity but high specificity for 
FIP . •  Culture—bacterial culture of CSF 
commonly unrewarding despite bacterial 
infection; fungal and viral culture unrewarding 
and potential zoonoses. •  Urine galactomannan 
assay (ELISA)—high sensitivity and specificity 
for Blastomyces , Aspergillus , and Histoplasma . 
• Blood/urine cultures—low sensitivity and 
specificity; may help discriminate agent in 
bacterial encephalitis and help in antibiotics 
choice. •  Rabies—no premortem diagnostic test.
IMAGING
• Thoracic radiographs—may reveal fungal/
toxoplasma infection or concurrent bacterial 
pneumonia. •  Spine radiographs—may reveal 
concurrent fungal/bacterial discospondylitis. 
• Brain MRI—shows focal/multifocal lesions. 
• Brain CT—may show focal/multifocal brain 
lesions; less sensitive and specific than MRI
• CSF cytology—used to confirm inflamm -
ation; may be normal if meninges not 
affected. ◦ Immune mediated—increased 
protein and cellular content (lymphocytes 
and/or macrophages), increased eosinophils in 
EME; predominantly neutrophilic in some 
cases. ◦ Viral—predominantly lymphocytic. 
◦ Bacterial—predominantly degenerated 
neutrophils. ◦ Fungal—mixed inflammation.

Canine and Feline, Seventh Edition  443
E
E• Infectious agent rarely seen (except 
Findings depend on specific type of immune-
mediated inflammation (e.g., granulomatous, 
necrotic) and infectious agent.
  TREATMENT
Inpatient medical management—may require 
initial intensive care management if elevated 
intracranial pressure.
• Increased intracranial pressure—hypertonic 
saline, mannitol, dexamethasone. •  Anti-
seizure treatment—diazepam, phenobarbital, 
levetiracetam in boluses or CRI. •  Analgesic 
medication—necessary if painful from 
associated meningitis: opioids, gabapentin. 
• Nursing care for nonambulatory patients—
bedding, switching sides, physiotherapy.
ACTIVITY
As tolerated.
DIET
No oral intake if unable to swallow, e.g., 
depressed, dysphagia, vomiting.
Relapse possible with both immune-mediated 
and infectious encephalitis.
Brain biopsy—may be needed in specific cases.
• Apply specific therapy once diagnosis is 
reached or highly suspected. •  Immune 
mediated—prednisone/prednisolone 2 mg/kg/
day until most of recovery achieved (usually 
1–2 weeks), then tapered progressively each 
month over 6 months; initially, dexamethasone 
0.25 mg/kg q24h can be given IV. •  Viral—no 
specific: treat symptomatically. •  Bacterial—
broad-spectrum IV antibiotics initially (e.g., 
fluoroquinolones + amoxicillin/clavulanate); 
continue PO depending on sensitivity or with 
broad-spectrum if agent unknown. •  Fungal—
itraconazole ( Aspergillus ), fluconazole (may be 
preferred if intra-axial), amphotericin B, 
voriconazole. •  Protozoal—clindamycin, 
trimethoprim/sulfamides. •  Rickettsial—
doxycycline. •  Parasitic—ivermectin, 
albendazole.
• Prednisone not to be used more than a few 
days if infectious. •  Puppies <6 months of 
age—doxycycline contraindicated. •  Puppies <8 months of age—enrofloxacin contra -
indicated. •  Cats - ocular toxicity with 
enrofloxacin > 5mg/kg/day.
Prior corticosteroid treatment may alter MRI 
and CSF results and decrease chance of 
• Some patients may have better response if 
treated with prednisone plus another 
immunosuppressive drug compared to 
prednisone alone; no increased benefits of 
using 3 or more drugs; second immuno -
suppressive drug progressively tapered once 
prednisone dose is 0.5 mg/kg/day. •  Cytosine 
arabinoside—first administration IV CRI 
100 mg/m2/24h for 24–48h, then 100 mg/m2 
IV CRI over 8–24h every 3 weeks for 6 
months; time between administration 
progressively lengthened thereafter; SC 
injection protocol exists but likely less 
efficient. •  Azathioprine—2 mg/kg PO 
q24h. •  Cyclosporine—5–10 mg/kg PO 
q12h. •  Mycophenolate—10–20 mg/kg PO 
q12h. •  Leflunomide—2–4 mg/kg PO q24h. 
• Radiation therapy—reported.
  FOLLOW-UP
• Frequent neurologic evaluations in first 
48–72 hours to monitor progress. •  Recheck 
CBC/biochemistry every month initially and 
then every 3–6 months while on immuno -
suppressive therapy. •  Relapse as medication is 
withdrawn—chance of relapse increased if 
abnormal recheck MRI and CSF before 
stopping treatment. •  Stop treatment for 
fungal diseases when antigen titers negative.
• Avoid outdoor roaming and use effective 
tick control in endemic areas. •  No definitive 
association between immune-mediated 
encephalitis and vaccination.
• General anesthesia and CSF collection—
contraindicated in unstable patients with 
increased intracranial pressure. 
• Immunosuppressive drugs—predispose to 
infections. •  Long-term corticosteroid 
therapy—signs of iatrogenic hyperadreno -
corticism and related side effects. •  Increased 
intracranial pressure—poor prognosis factor, 
increased chance of death early in course of 
disease.
• Resolution progressive—2–8 weeks. 
• Rickettsial, bacterial, protozoal—fair 
chance of survival if treated early. •  Fungal, 
algal, viral—almost always fatal. •  Immune 
mediated—necrotic encephalitis has worse prognosis. •  Idiopathic tremor syndrome—
excellent prognosis with complete resolution.
• Rabies—consider in endemic areas if patient 
is outdoor animal that has rapidly progressive 
encephalitis. •  Humans may be infected by 
the same vector tick that affected the patient. 
• Exudates and diagnostic samples from 
animals with mycosis can be contagious.
SYNONYMS
• Meningoencephalitis of unknown etiology 
(MUE). •  Idiopathic tremor syndrome—
white shaker syndrome.
SEE ALSO
• Seizures (Convulsions, Status 
Epilepticus)—Cats.
Epilepticus)—Dogs.
• Stupor and Coma.
• Vestibular Disease, Geriatric—Dogs.
• Vestibular Disease, Idiopathic—Cats.
• CSF = cerebrospinal fluid. •  EME = 
eosinophilic meningoencephalitis. •  FeLV = 
feline leukemia virus. •  FIP = feline infectious 
peritonitis. •  FIV = feline immunodeficiency 
virus. •  GME = granulomatous meningo -
encephalitis. •  Ig = immunoglobulin. •  MUE 
= meningoencephalitis of unknown etiology. 
• MUO = meningoencephalitis of unknown 
origin. •  NLE = necrotizing leukoencephalitis. 
• NME = necrotizing meningoencephalitis.
Bentley RT, Taylor AR, Thomovsky SA. 
Fungal infections of the central nervous 
system in small animals. Vet Clin North Am 
Small Anim Pract 2018, 48:63–83.
Coates JR, Jeffery ND. Perspectives on 
meningoencephalomyelitis of unknown 
origin. Vet Clin North Am Small Anim 
Pract 2014, 44:1157–1185.
Cornelis I, Van Ham L, Gielen I, et al. 
Clinical presentation, diagnostic findings, 
prognostic factors, treatment and outcome 
in dogs with meningoencephalomyelitis of 
unknown origin: a review. Vet J 2019, 
244:37–44.
Sykes JE, Greene CE. Infectious Diseases of 
Elsevier Health Sciences, 2011.
Author  Thomas Parmentier
Allen Franklin Sisson.
available online(continued)  Encephalitis

444  Blackwell’s Five-Minute Veterinary Consult  
EEncephalitis Secondary to Parasitic Migration
  BASICS
OVERVIEW
• Aberrant parasitic migration into the CNS.
• Parasites usually affect another organ system 
of the same host (e.g., Dirofilaria immitis , 
T aenia , Ancylostoma caninum , Angiostrongylus , 
or Toxocara canis ) or a different host species 
(e.g., raccoon roundworm, Baylisascaris 
procyonis ; skunk roundworm, B. columnaris ; 
Coenurus  spp.; or Cysticercus cellulosae ).
• Access to CNS—hematogenously (dirofila-
riasis) or through adjacent tissues, including 
the middle ear, skull foramina, cribriform 
plate through nasal cavities, or open 
fontanelles (cuterebraiasis).
• Dirofilariasis—adult animals only.
• Other parasites—young dogs and cats with 
access to outdoors: rare and sporadic occurrence.
SIGNS
• Vary with the portion of CNS affected.
• Likely asymmetric.
• May suggest a focal mass lesion or a 
multifocal disease process.
• Cuterebriasis—seasonal (July–October) 
acute or peracute onset of behavior changes, 
seizures, visual deficits, etc.; previous history 
of respiratory disease is common.
• Rat parasite, Angiostrongylus cantonensis  
(Australia)—lumbosacral syndrome (hind 
limbs, tail, and bladder paralysis/paresis) in 
puppies that may ascend to thoracic limbs 
and cranial nerves.
Housing in a cage previously occupied by 
wildlife (raccoons, skunks).
  DIAGNOSIS
• Rule out other causes of focal encephalopathy—  
infectious diseases (viral, bacterial, protozoan, 
or fungal); granulomatous 
meningoencephalomyelitis; brain tumor.
• Diagnosis often made on necropsy.
Normal unless the parasite also affects 
non-neural tissues.
Cerebrospinal fluid (CSF)—may show 
eosinophilic, neutrophilic, or mononuclear 
pleocytosis (also found in protozoal, fungal, 
and prototheca encephalitides); may be 
normal (strictly parenchymal lesions).
IMAGING
CT or MRI—brain; focal lesion and/or 
cerebral infarction from occlusion of cerebral vessels. Nonspecific and often inconclusive, 
but could lead to surgical exploration and 
removal of migrating parasite.
• The parasite or its tracts may or may not be 
• Infarction, vascular rupture, and hemor-
rhage or vascular emboli may cause local to 
extensive necrosis and malacia; there may be 
granulomatous proliferation or/and obstruc-
tive hydrocephalus.
• Dirofilaria immitis —intravascular or 
extravascular.
• Worms produce focal inflammation.
• Cuterebriasis is the suspected cause of feline 
ischemic encephalopathy.
  TREATMENT
• Surgical removal of intracranial cuterebra.
• Parasiticides (see below) could potentiate 
illness.
• Supportive and nursing care.
• Dirofilariasis and neural angiostrongylosis—
anthelmintic treatment may cause worsening 
of signs and sometimes death.
• Mild neural angiostrongylosis—puppies 
may recover with supportive care and 
corticosteroid therapy.
• A single dose of ivermectin (400 mg/kg SC) 
may kill cuterebra larvae in cats with 
suspected cuterebriasis; pretreatment with 
diphenhydramine (4 mg/kg) and intravenous 
dexamethasone (0.1 mg/kg) may mitigate 
allergic/anaphylactic reactions to dead or 
dying larvae.
• T reat inflammation and secondary 
infections—corticosteroids/nonsteroidal 
anti-inflammatory drugs (NSAIDs), 
  FOLLOW-UP
As necessary.
• Keep pets indoors or/and segregated from 
wildlife.
• Use preventive anthelmintics and 
dirofilaricides.
Acute or insidious onset, then usually 
progressive.  MISCELLANEOUS
SEE ALSO
• Encephalitis.
• Feline Ischemic Encephalopathy.
• Heartworm Disease—Dogs.
drug.
Braund KG. Neurovascular disorders. In: Vite 
CH, ed., Clinical Neurology in Small 
Animals—Localization, Diagnosis and 
diagnosis-and-treatment/neurovascular
Dewey CW. Verminous encephalitis. In: 
Dewey CW, ed., A Practical Guide to 
Canine and Feline Neurology, 2nd ed. 
Ames, IA: Wiley-Blackwell, 2008, 
pp. 184–185.
Glass EN, Cornetta AM, deLahunta A, et al. 
Clinical and clinicopathologic features in 11 
cats with Cuterebra Larvae myiasis of the 
central nervous system. J Vet Intern Med 
1998, 12:365–368.
James FMK, Poma R. Neurological manifes-
tations of feline cuterebriasis. Can Vet J 
2010, 51:213–215.
Vite CH. Inflammatory diseases of the central 
nervous system. In: Vite CH, ed., Clinical 
Neurology in Small Animals—Localization, 
Diagnosis and T reatment. Ithaca, NY: IVIS, 
2005.
Williams KJ, Summers BA, de Lahunta A. 
Cerebrospinal cuterebriasis in cats and its 
association with feline ischemic encepha-
lopathy. Vet Pathol 1998, 35:330–343.
Author  Christine F . Berthelin-Baker

Canine and Feline, Seventh Edition  445
EEndocarditis, Infective
  BASICS
The invasion of the cardiac endocardium, 
usually the valves, by infectious agents. 
Usually Gram-positive bacteria, especially 
staphylococci or streptococci. Occasionally 
Rickettsia  or Bartonella  in dogs. Rarely fungi 
in dogs. Culture-negative cases may be due to 
Bartonella  or fungi (e.g., Aspergillus ). Less 
likely due to Brucella , Coxiella , 
Corynebacterium , and Chlamydia .
• Bacteremia from various portals of entry; 
bacteria invade and colonize the heart 
valves—usually the aortic, occasionally the 
mitral, and rarely the tricuspid and pulmonic 
valves. • Endocardial ulceration exposes 
collagen causing platelet aggregation, 
activation of the coagulation cascade, and 
formation of vegetations. • Vegetations on 
heart valves are composed of an inner layer of 
platelets, fibrin, red blood cells, and bacteria; 
a middle layer of bacteria; and an outer layer 
of fibrin. • Valvular insufficiency develops in 
virtually all patients; aortic insufficiency 
almost invariably leads to intractable 
left-sided congestive heart failure (CHF) 
within weeks to several months. • CHF is less 
frequent and latent when only the mitral 
valve is affected. • Vegetative lesions may 
dislodge causing infarction or metastatic 
infection to any organ; organs commonly 
infected include the spleen, kidneys, brain, 
and skeletal muscles.
• Cardiovascular—valvular insufficiency; 
arrhythmias, myocarditis. • Nervous—para/
tetraparesis; cranial nerve deficits; abnormal 
mentation. • Hemic/lymphatic/immune— 
hypercoagulation; disseminated intravascular 
coagulation. • Musculoskeletal—septic or 
immune-mediated polyarthropathy; hyper  - 
trophic osteopathy; discospondylitis. • Renal/
urologic—renal infarction; immune-mediated 
glomerulonephritis; urinary tract infections. 
• Respiratory—pulmonary edema and/or 
emboli.
Species
Dog; rarely cat.
• Medium to large breeds. • Breeds 
predisposed to subaortic stenosis (SAS).
Most affected dogs are 4–8 years of age; 
infection can occur at any age.
Most studies report male predominance—
may be as great as 2 : 1.SIGNS
• Gram-negative bacteremia results in peracute 
or acute signs; Gram-positive bacteremia results 
in subacute or chronic clinical signs. • Systemic 
signs secondary to infarction, infection 
(inflammation), toxemia, or immune-mediated 
damage; usually override cardiac signs.
• Infectious disease involving skin, oral, 
gastrointestinal (GI), or genital tracts (e.g., 
prostatitis). • Predisposing factors— 
immunosuppressive drug therapy, SAS, recent 
surgery, infected wound, abscess, pyoderma, or 
recent implantation of cardiovascular device 
(i.e., pacemaker, Amplatz® canine ductal 
occluder). • Presenting complaints include 
lethargy, paresis, fever, anorexia, GI disturbance, 
and lameness; in cats, cardiac decompensation 
and/or locomotor abnormalities are common 
presenting complaints.
• Usually diverse and misleading—the “great 
imitator.” • Pyrexia and general malaise. 
• Dyspnea due to CHF . • Arrhythmias 
(ventricular, supraventricular, or heart block). 
• Single or shifting leg lameness. • Systolic 
heart murmur. • “To-and-fro” murmur—
associated with aortic valve vegetation causing 
systolic turbulence and diastolic regurgitation. 
• Diastolic murmur with hyperdynamic 
femoral pulses are a strong indication of 
advanced aortic endocarditis.
CAUSES
• Bacterial infection associated with oral 
cavity, bone, prostate, skin, and other sites. 
• Invasive diagnostic or surgical procedures 
causing bacteremia.
• SAS. • Immunosuppression from long-
term or high-dose corticosteroids, neoplasia, 
or cytotoxic drug administration.
  DIAGNOSIS
• Bacteremia of any cause. • Polysystemic, 
immune-mediated disorders. • Left-sided CHF 
caused by dilated cardiomyopathy or SAS.
• Inflammatory leukogram (i.e., neutrophilia, 
left shift, and monocytosis)—patients with 
chronic, relatively inactive, or walled-off 
infection may have normal or nearly normal 
leukogram; those with chronic infection may 
have mature neutrophilia with monocytosis. 
• Nonregenerative anemia. 
• Thrombocytopenia—variable severity. 
• Low-normal or low albumin, low-normal or 
low glucose, and high serum alkaline phosphatase/  
bilirubin activity are inconsistently associated with sepsis (septic triad). • Renal azotemia—
secondary to renal emboli, pyelonephritis, and/
or hypovolemia-induced renal failure. 
• Proteinuria caused by septic emboli, 
immune-mediated glomerulonephritis, or renal 
infarction; hematuria, pyuria, and granular 
casts associated with pyelonephritis.
• Blood culture—three samples taken at least 1 
hour apart over 24 hours; at least two should 
yield the same microbe; both aerobic and 
anaerobic cultures recommended; antibiotic 
removal systems available for diagnosis of 
patients given antibiotics. • PCR with bacterial 
16s primers, in combination with blood 
culture, increases likelihood of identification of 
bacteremia. • Culture-negative bacteremia 
often due to prior antibiotic administration or 
fastidious microbes, especially Bartonella . 
• Catheter tips—culture. • Urine culture (not 
a substitute for blood culture)—easy; often 
positive; does not necessarily incriminate the 
urinary tract as the source of infection. • Tests 
for prostate, kidney, and bone infection may be 
warranted. • Positive antinuclear antibody, 
lupus erythematosus, rheumatoid factor, and 
Coombs’ test results occasionally found—
nonspecific; tend to confound the diagnosis. 
• Bartonella alpha-Proteobacteria growth 
medium (BAPGM) and PCR—for Bartonella .
IMAGING
Left cardiomegaly; rarely, calcification of one 
or more heart valves.
Best test—vegetative aortic endocarditis easily 
discerned; mitral valve infection may be 
difficult to differentiate from degenerative 
valve disease; hyperechoic with chronicity.
Arthrocentesis
Joint taps for cytology and culture—cytology 
usually does not differentiate septic from 
immune-mediated arthritis; either, though 
usually not septic, can exist with infective 
endocarditis; usually nondegenerate neutro-
phils regardless of cause.
ECG
• May be normal; occasionally reflects left 
cardiomegaly; often detects ventricular 
tachyarrhythmias; occasionally heart block of 
variable severity or supraventricular 
tachyarrhythmias. • Heart block suggests 
aortic valve involvement with infection or 
infarction of the adjacent septum.
• Cardiomegaly, almost always left sided 
when present. • Vegetations and thrombi on 
one or more valves. • Infection, hemorrhage, 
and infarction of adjacent myocardium. 
• Renal infarcts usually present. • Primary or 
secondary sites of infection, especially

446  Blackwell’s Five-Minute Veterinary Consult  
Ekidneys and spleen. • Pulmonary hemorr -
hage or edema.
  TREATMENT
Early index of suspicion with aggressive, rapid 
diagnostic testing, followed by appropriate 
treatment are imperative for cure. Cure is a 
reasonable expectation when mitral valve 
(alone) endocarditis is identified early in its 
course and treatment is aggressive.
• Aggressive fluid therapy—overt or 
impending CHF limits fluid volumes that can 
be administered; this problem is virtually 
insurmountable in patients with concomitant 
renal failure. • Imminent CHF—provide no 
more than maintenance volumes of fluid; 
alternate 5% dextrose in water (D5W) with 
lactated Ringer’s solution (LRS; or 2.5% 
dextrose in half-strength LRS); potassium 
supplementation usually required.
Guarded prognosis if only mitral valve 
involved. Grave prognosis if aortic valve is 
involved.
T reatment variable—depends on severity of 
sepsis and presence or absence of CHF .
• Backbone of treatment but usually do not 
eradicate infection before irreversible aortic 
valve damage occurs; more than minimal 
damage to the aortic valve is life-threatening 
because aortic insufficiency tends to be a 
lethal complication. • High-dose IV 
administration of bactericidal antibiotics is 
imperative and recommended for as long as 
feasible (at least 1 week), followed by SC 
administration for 1 or more weeks. • Oral 
administration—recommended only after at 
least 4 weeks of injectable therapy and at 
least 1 week after hematologic and clinical 
signs of infection and inflammation have 
disappeared; long-term ( >4 months) 
treatment may be required to eradicate the 
infection from vegetations. • Selection 
determined by both urgency of septic 
complications and results of bacterial 
culture; coagulase-positive staphylococci 
and streptococci are most often incrim -
inated, so choices can be logically made 
before culture results are obtained. 
• Coagulase-positive staphylococci—usually 
resistant to penicillin, hetacillin, amoxicillin, 
and ampicillin. • Streptococci—often 
resistant to aminoglycosides and fluoroquinolones. • Gram-negative 
bacteria—often sensitive to third-generation 
cephalosporins, fluoroquinolones, and 
aminoglycosides. • Bartonella —only 
aminoglycosides appear bactericidal; can try 
doxycycline, fluoroquinolone, rifampin, or 
azithromycin. • First-generation 
cephalosporins—reasonable choice for 
stable patients until culture results are 
obtained. • T reat life-threatening sepsis 
immediately with drug combinations; 
pending culture results, one of three 
regimens is recommended: ◦ Penicillin, 
ampicillin, ticarcillin, or a first-generation 
cephalosporin is combined with an 
aminoglycoside; aminoglycosides are not 
good choices for animals with overt or 
impending CHF or those with renal 
azotemia; gentamicin (2 mg/kg q8h) is 
recommended for only 5–10 days because 
of renal toxicity; a fluoroquinolone may be 
substituted for an aminoglycoside. 
◦ Clindamycin (2–10 mg/kg IV q8h) plus 
enrofloxacin (10 mg/kg q24h given diluted 
1 : 1 in sterile water and injected slowly 
over 15–20 min). ◦ Advanced-generation 
cephalosporins or ticarcillin–clavulanic acid 
(Timentin®)—high dosages, but only 
normal dosages if patient has renal failure.
Treatment of CHF
• Pimobendan, angiotensin-converting 
enzyme inhibitor, spironolactone, and 
furosemide (± amlodipine) indicated for 
patients with overt or impending CHF . 
• Oxygen, high-dose furosemide—2–8 mg/
kg IV (± nitroglycerin and/or hydralazine 
1–2 mg/kg q12h) for patients with acute, 
severe pulmonary edema.
• Avoid antibiotics that cannot penetrate 
fibrin (e.g., sulfonamides). • Corticosteroids.
• Anticoagulant therapy—controversial in the 
prevention of embolization; heparin not 
recommended in human medicine as it 
increases risk of hemorrhage. • Aspirin 
(5–7 mg/kg PO q24h) and/or dalteparin 
(100 U/kg SC q8h) and/or clopidogrel 
(2–4 mg/kg PO q24h)—may reduce bacterial 
dissemination and embolization.
  FOLLOW-UP
• Emergence of antibiotic resistance—
relapsing fever and inflammatory leukogram; 
imperative to adjust treatment based on 
culture results. • Frequent examination and 
CBC after discharge. • Repeat blood cultures 
1 week after antibiotics are discontinued or if 
fever recurs.PREVENTION/AVOIDANCE
• Indwelling catheters—restrict to 
appropriate indications; aseptic placement; 
replace within 3–5 days. • Administer 
antibiotics to dogs with moderate to severe 
SAS during dentistry or “dirty” procedures. 
• Avoid careless use of corticosteroids.
• CHF . • Renal failure. • Septic embolization 
of many tissues and organs. • Persistent or 
latent immune-mediated polyarthropathy.
• Best prognosis associated with short history 
of bacteremia, rapid diagnosis, and aggressive 
treatment; given that diagnosis is often 
delayed in cats, prognosis is often grave. 
• Mortality relatively higher in animals 
recently given corticosteroids. • Grave 
prognosis for patients with aortic valve 
endocarditis. • Patients with mitral valve 
endocarditis can be saved with appropriate 
treatment. • Latent CHF can occur with 
advanced, late diagnosis, or inadequate 
treatment for mitral valve endocarditis.
Congenital heart defects (usually SAS) in 
some animals.
SYNONYMS
• Bacterial endocarditis. • Vegetative 
SEE ALSO
• Bartonellosis. • Congestive Heart Failure, 
Left-Sided. • Discospondylitis. • Prostatitis 
and Prostatic Abscess. • Sepsis and Bacteremia.
• BAPGM = Bartonella alpha-Proteobacteria 
growth medium. • CHF = congestive heart 
failure. • D5W = 5% dextrose in water.  
• GI = gastrointestinal. • LRS = lactated 
Ringer’s solution. • SAS = subaortic stenosis.
Calvert C, Thomason J. Cardiovascular 
Diseases of the Dog and Cat. St. Louis, 
MO: Saunders Elsevier, 2012: 912–936.
Palerme JS, Jones AE, Ward JL, et al. 
Infective endocarditis in 13 Cats. J Vet 
Cardiol 2016, 18:213–225.
Author  Justin D. Thomason
Clay A. Calvert
available onlineEndocarditis, Infective  (continued)

Canine and Feline, Seventh Edition  447
EEndomyocardial Diseases—Cats
  BASICS
OVERVIEW
• Endomyocarditis—acute cardiopulmonary 
disease that typically develops following a 
stressful event; characterized by interstitial 
pneumonia and endomyocardial inflamma-
tion; pneumonia is usually severe and 
commonly causes death; one report recorded 
the incidence of endomyocarditis at postmor-
tem to be equivalent to that of hypertrophic 
• Endocardial fibroelastosis—congenital 
heart disease in which severe fibrous endo  - 
cardial thickening leads to heart failure 
secondary to diastolic and systolic failure.
• Excessive moderator bands (EMBs)—a rare 
and unique pathologic disease; moderator 
bands are normal muscular bands in the right 
ventricle, but they can sometimes occur in the 
left ventricle.
• Cats.
• Endomyocarditis—predominantly males 
(62%) age 1–4 years.
• Endocardial fibroelastosis—early development 
of biventricular or left heart failure, usually 
prior to 6 months of age.
• EMBs—can be seen in any age of cat.
SIGNS
Endomyocarditis
• Dyspnea following a stressful event in a 
young, healthy cat.
• Respiratory signs usually occur 5–21 days 
after the stressor.
• In one report, 73% of cases presented 
between August and September.
Endocardial Fibroelastosis and EMBs
• Lethargy, weakness, collapse, syncope.
• Poor appetite and weight loss.
• Dyspnea.
• Paresis or paralysis; signs of thromboem-
bolic disease.
• Severe dyspnea.
• Occasional crackles.
• May have murmur or gallop; murmur may 
vary in intensity.
• May have evidence of thromboembolic disease.
• Typically no significant abnormalities prior 
to the stressful event.
• Gallop.
• Systolic murmur, possible mitral 
regurgitation.• Dyspnea and increased lung sounds or 
crackles.
• Paresis or paralysis with weak or absent 
femoral pulses.
• Arrhythmias possible.
• Cause unknown for all three diseases.
• Risk factors for endomyocarditis include 
stressful incidents such as anesthesia 
(commonly associated with neutering or 
declawing), vaccination, relocation, or 
bathing.
• Endocardial fibroelastosis may be familial 
in Burmese and Siamese cats.
• Appearance of EMBs in a young cat would 
suggest a congenital malformation.
  DIAGNOSIS
Other Causes of Cardiac Disease
• Unclassified cardiomyopathy.
• Restrictive cardiomyopathy.
• Dilated cardiomyopathy.
• Congenital heart malformations.
Other Causes of Dyspnea
• Other forms of cardiac disease as above.
• Primary respiratory disease.
• Pleural space disease.
• Mediastinal disorders, infection, trauma, 
• Hemoglobin disorders, anemia, methemo-
globinemia, causes of central cyanosis.
Other Causes of Collapse, Weakness, or 
Syncope
• Neurologic or musculoskeletal disease.
• Metabolic disease or electrolyte disorders.
• Other forms of paresis or paralysis.
• Arterial thromboembolism secondary to 
any form of cardiac disease or neoplasia.
Not diagnostic.
N/A
IMAGING
Thoracic Radiographic Findings for All 
Three Diseases
• Cardiomegaly.
effusion if congestion has developed.
• Normal to mildly large left atrium.
• Left ventricular wall thickness can be 
normal to mildly thick (0.6–0.7 cm).• Hyperechoic endomyocardium reported— 
incidence seems to vary and is subjective; in 
one report it was as high as 86%.
Endocardial Fibroelastosis
• Limited data available.
• Reduced left ventricular function and 
enlarged left atrium.
EMBs
Many findings can overlap with restrictive 
cardiomyopathy. A network of false tendons 
can sometimes be imaged with 2D echo- 
cardiography.
• Endomyocarditis—sinus tachycardia 
common; ventricular premature complexes, 
atrial premature complexes, bundle branch 
block, and complete atrioventricular (AV) 
block reported.
• Endocardial fibroelastosis—evidence for 
left-sided enlargement; sinus rhythm typically 
present, but various arrhythmias possible.
• EMBs—various electrocardiographic 
findings have been reported: AV block, sinus 
bradycardia, right bundle branch block, and 
left axis deviation.
• Interstitial pneumonia.
• Left heart enlargement and opacity of the 
left ventricular endomyocardium with foci of 
hemorrhage; fibroplasia of the endocardium 
is striking.
• Varying degrees of endomyocardial 
inflammation with infiltrates of neutrophils, 
lymphocytes, plasma cells, histiocytes, and 
macrophages seen histologically.
• Left ventricular and atrial dilation with 
severe diffuse white opaque thickening of the 
endocardium.
• Diffuse hypocellular, fibroelastic thickening 
of the endomyocardium; prominent endo -
myocardial edema with dilation of lymphatics.
EMBs
Changes typically include an irregular left 
ventricular endocardial contour with a rounded 
apex and numerous irregular left ventricular 
false tendons; heart weight can be greater than 
normal; the moderator bands are composed of 
central Purkinje fibers and collagen.
  TREATMENT
• No single therapy protocol to date.
• Small percentage of cats have survived; 
these cats do not require long-term 
therapy.

448  Blackwell’s Five-Minute Veterinary Consult  
E• Supportive care with oxygen and possibly 
ventilation.
• Oxygen therapy via cage delivery is least 
stressful.
• Thoracocentesis if pleural effusion.
Steroids, furosemide, and vasodilators have 
been tried, but efficacy is unknown.
Endocardial Fibroelastosis and EMBs 
with Acute Congestive Heart Failure 
(CHF)
0.5–1 mg/kg IV/IM q1–6h.
• Dermal application of 2% nitroglycerin 
ointment one-eighth to one-fourth inch 
q4–6h has been suggested but is of unknown 
efficacy.
• Arrhythmias may resolve with stabilization. 
If there is rapid atrial fibrillation (heart rate 
>200), a calcium channel blocker or beta 
blocker can be considered to control the 
ventricular response. If there is dilated 
cardiomyopathy, digoxin may be a better 
choice for controlling the atrial fibrillation 
rate. For other supraventricular (SV) 
arrhythmias and ventricular arrhythmias, 
waiting for a response to heart failure therapy may be wise before starting antiarrhythmic 
therapy.
• Intractable edema—nitroprusside 1–5  μg/
kg/min may be helpful.
Chronic CHF
• T reat as other CHF , with furosemide and 
angiotensin-converting enzyme inhibitors 
(e.g., enalapril, benazepril).
• Digoxin can be added for SV arrhythmia 
control when patient is stable and eating.
N/A
  FOLLOW-UP
EXPECTED COURSE AND P 
ROGNOSIS
• Endomyocarditis—poor, although some 
animals survive; animals that survive 
respiratory phase may progress to left 
ventricular endocardial fibrosis.
• Endocardial fibroelastosis and EMBs—
medical treatment of CHF may prolong life, 
but recovery is unlikely.
• Aortic thromboembolism.
• Relationship possible between endomyocar-
ditis and left ventricular endocardial fibrosis. SEE ALSO
• EMB = excessive moderator band.
• SV= supraventricular.
Bossbaly MB, Stalis I, Knight D, Van Winkle 
T. Feline endomyocarditis: a clinical/
pathological study of 44 cases. Proceedings 
of the 12th ACVIM Forum, 1994, p. 975.
Liu S, Tilley LP . Excessive moderator bands in 
the left ventricle of 21 cats. JAVMA 1982, 
180:1215–1219.
Stalis IH, Bossbaly MJ, Van Winkle TJ. 
Feline endomyocarditis and left ventricular 
endocardial fibrosis. Vet Pathol 1995, 
32(2):122–126.
Wray JD, Gajanayake I, Smith SH. 
Congestive heart failure associated with a 
large transverse left ventricular moderator 
band in a cat. J Feline Med Surg 2007, 
9:56–60.
Author  Carl D. Sammarco
Consulting Editors  Michael AherneEndomyocardial Diseases—Cats  (continued)

Canine and Feline, Seventh Edition  449
EEntropion
  BASICS
OVERVIEW
• Inversion or rolling in of eyelid margin, 
resulting in frictional irritation of cornea and/
or conjunctiva from contact with outer 
surface of eyelid.
• May result in keratitis, corneal ulceration, 
or corneal perforation.
• Severe corneal disease may threaten vision.
• Common in dogs—seen in chow chow, 
Chinese Shar-Pei, Norwegian elkhound, 
sporting breeds (e.g., spaniel, retriever), 
brachycephalic breeds, toy breeds, and giant 
breeds; age—puppies as early as 2–6 weeks 
old; usually identified in dogs <1 year old.
• Cats—usually in brachycephalic breeds, in 
young cats due to chronic ocular surface disease, 
and older animals due to retrobulbar fat loss.
SIGNS
• Mild, medial—chronic epiphora and 
medial pigmentary keratitis (toy dogs and 
brachycephalic dogs and cats).
• Mild, lateral—chronic mucoid to mucopurulent 
ocular discharge (giant-breed dogs).
• Upper lid, lower lid, or lateral canthal—
severe blepharospasm, purulent discharge, 
pigmentary or ulcerative keratitis, potential 
cornea rupture (chow chow, shar-pei, 
bloodhound, sporting breeds).
• Cats—often have associated keratoconjunc-
tivitis, corneal ulceration, or corneal 
sequestrum (brown-black corneal opacity).
• Genetic predisposition—based on facial 
conformation and eyelid support.
• Brachycephalic breeds (dogs and cats)—
excessive tension on ligamentous structures of 
medial canthus plus nasal folds and facial 
conformation results in rolling inward of 
medial aspects of upper and lower eyelids at 
the medial canthus.
• Giant breeds and breeds with excessive eyelid 
length (macroblepharon), heavy/loose facial 
skin, or excessive facial folds—laxity of lateral 
canthus allows entropion of upper and lower 
eyelids and lateral canthus.
• Spastic entropion—from ocular irritation 
(e.g., distichia, ectopic cilia, trichiasis, foreign 
body, irritant conjunctivitis); leads to excessive 
• Non-predisposed breeds—may be primary 
irritant causing secondary spastic entropion.
• Loss of orbital fat or periorbital musculature 
may lead to enophthalmos and entropion.
• Secondary cicatricial entropion—from 
scarring due to eyelid wounds or eyelid surgery.
• Cats—chronic infectious conjunctivitis or 
keratitis: may lead to functional entropion caused by chronic blepharospasm (spastic 
entropion); also in older cats due to 
enophthalmos from retrobulbar fat loss.
  DIAGNOSIS
• Underlying causes of spastic entropion 
(eyelid hair anomalies, foreign bodies, 
infectious keratitis/conjunctivitis) should be 
ruled out and corrected, if possible, before an 
attempt at surgical correction is made.
• Puppies—common for first-time breeders of 
chow chows and Chinese Shar-Peis to mistakenly 
think that eyelids have not opened at 4–5 weeks 
of age, when puppies actually have severe 
blepharospasm and spastic entropion.
N/A
N/A
IMAGING
N/A
• Observe patient with minimal restraint to 
assess degree of entropion without distortion 
from tension on eyelids or periocular area.
• Apply a topical anesthetic to reduce spastic 
component to differentiate spastic versus 
physiologic entropion.
  TREATMENT
Puppies
• Do not initially perform skin resection 
surgery.
• If cornea ulcerated—topical antibiotic (e.g., 
neomycin/polymyxin B/bacitracin) ointment 
q6–8h.
• If mildly entropic and cornea not ulcerated, 
lubricate with artificial tear ointment q8–12h.
• If moderate to severe entropion with or 
without corneal ulceration, temporarily evert 
eyelid margins with sutures to break the 
irritation–spasm cycle; if successful, 
permanent procedure is unnecessary; may 
need to be repeated every 2–4 weeks until 
adult facial conformation is achieved.
• Semi-permanent eyelid eversion with 
hyaluronic acid filler injection—lasts up to 
several months, often until adult facial 
conformation is achieved.
• Permanent skin resection technique—
postponed until patient’s facial conformation 
matures (usually 1.5–2 years).
Medial Entropion
• Temporary eversion of medial canthus with 
sutures may aid in determining contribution 
of medial entropion to epiphora.• Medial canthoplasty should be considered if 
entropion results in pigmentary keratitis, 
chronic epiphora, or corneal scarring.
Mature Dogs and Cats
• Chronic entropion—requires eyelid 
margin–everting surgery; ranges from simple 
Hotz-Celsus procedure to more radical lateral 
canthoplasty procedures; often combined 
with lid-shortening procedures.
• No history of previous entropion and 
clinical signs of acute condition—identify 
cause of spastic condition and correct; may 
attempt temporary eversion sutures before 
permanent skin resection.
• Topical ophthalmic ointment—triple 
antibiotic (in dogs only, q6–12h) or antibiotic 
based on culture and sensitivity testing; may 
be used if cornea is ulcerated, postoperatively, 
or as presurgical lubricant.
• Topical petrolatum-based artificial tear 
ointments (e.g., Puralube® q8–12h) may be 
used temporarily in mild cases without 
corneal ulceration.
N/A
  FOLLOW-UP
Temporary eversion suture technique—entro-
pion may revert when sutures are removed or 
spontaneously pull through the skin; repeat as 
necessary until patient is mature enough to 
undergo more permanent repair. Consider 
hyaluronic acid filler injection as alternative.
Wiley-Blackwell, 2013, pp. 843–864.
Williams DL, Kim JY. Feline entropion: a case 
series of 50 affected animals (2003–2008). 
Vet Ophthalmol 2009, 12(4):221–226.
J. Phillip Pickett.

450  Blackwell’s Five-Minute Veterinary Consult  
EEosinophilia
  BASICS
OVERVIEW
• Eosinophilia refers to an increased number 
of circulating eosinophils.
• Reference intervals may be difficult to 
accurately determine, as numbers do not tend 
to have normal (Gaussian) distribution. 
Absolute counts >1.5 x 103/μl often indicate 
clinically significant eosinophilia.
• Diseases associated with eosinophilia are 
highly variable. However, they often 
involve those causing release of cytokines 
including IL-5, IL-2, IL-3, and/or GM-CSF .
• Prevalence varies; 4.8% of cats and 10% of 
dogs have been identified with eosinophilia in 
large retrospective studies.
• Breed and sex predilections are directly 
correlated to the characteristics of specific 
diseases.
• Rottweilers and German shepherd dogs show 
the highest overall prevalence of eosinophilia.
SIGNS
• Clinical signs directly associated with 
eosinophilia per se are lacking.
• Specific clinical signs are dependent on the 
disease causing the eosinophilia.
widely variable and can be categorized in 
many ways.
• Infectious diseases typically involve tissues 
rather than peripheral blood, and are more 
likely to be parasitic than bacterial.
• Tissues involved are frequently those that 
contain abundant mast cells, such as skin, 
lungs, and intestine, and often involve 
• Metabolic—hypoadrenocortisim.
• Neoplastic—mast cell tumor; eosinophilic 
leukemia; lymphoma (both T-cell and B-cell); 
thymoma; mammary carcinoma; oral 
fibrosarcoma; transitional cell carcinoma.
• Immune mediated—hypereosinophilic 
syndrome (HES); idiopathic HES in 
Rottweilers; feline asthma; eosinophilic 
bronchopneumopathy; feline gastro -
intestinal eosinophilic sclerosing 
fibroplasia; flea bite allergy; eosinophilic 
granuloma complex.
• Infectious— Angiostrongylus vasorum ; 
heartworm disease ( Dirofilaria immitis ); 
Ehrlichia  spp. infections; Anaplasma  spp. 
infections; histoplasmosis; sarcocytosis; 
Aelurostrongylus  spp.; larval migration of 
various parasites.
• Toxic methimazole therapy.  DIAGNOSIS
• HES represents an idiopathic response that 
may be due to an occult immunologic stimulus.
• Eosinophilic leukemia is a myeloproliferative 
disease that often has immature forms in 
circulation and in the bone marrow.
• Differentiation between HES and 
eosinophilic leukemia can be extremely 
difficult and is somewhat controversial.
• Caution should be taken in interpreting 
the results of some in-house hematology 
analyzers, as they only show good correlation 
with gold standard instruments. A blood 
smear should always  be evaluated as part of 
the CBC.
• Eosinophils tend to be larger and 
hypolobulated compared to neutrophils.
• Feline eosinophils have small, rod-shaped 
granules.
• Sight hounds and sporadic other individuals 
have “gray eosinophils,” which have poorly 
staining granules and occasionally empty 
vacuoles in their cytoplasm.
• Eosinophils are grouped into one large 
category; bands, metamyelocytes, etc. are 
typically not divided out, as they are with 
Additional testing (e.g., adrenocorticotropic 
hormone (ACTH) stimulation test, fecal 
flotation, cytology, etc.) are dependent on the 
differential diagnosis/disease in question.
IMAGING
Diagnostic imaging utilized (e.g., radio-
graphs, ultrasound, CT, etc.) is dependent on 
the differential diagnosis/disease in question.
Diagnostic procedures utilized (e.g., 
transtracheal wash, endoscopy, serologic 
testing, biopsy, etc.) are dependent on the 
• No specific lesions are ascribed solely to 
eosinophilia other than peripheral blood 
findings.
• Lesions are dependent on the disease(s) present.
  TREATMENT
• No specific treatment is described 
exclusively for eosinophilia.
• The treatment employed is dependent on 
the cause of the eosinophilia.  MEDICATIONS
Dependent on cause.
  FOLLOW-UP
SEE ALSO
Hypereosinophilic Syndrome (HES).
• HES = hypereosinophilic syndrome.
Center SA, Randolph JR, Erb HN, Reiter S. 
Eosinophilia in the cat: a retrospective study 
of 312 cases. J Am Anim Hosp Assoc 1990, 
26(4):349–358.
Lillieöök I, Gunnardsson L, Zakrisson G, 
Tvedten H. Diseases associated with 
pronounced eosinophilia: a study of 105 
dogs in Sweden. J Small Anim Pract 2000, 
41(6):248–253.
Lillieöök I, Tvedten H. Investigation of 
hypereosinophilia and potential treatments. 
Vet Clin North Am Small Anim Pract 2003, 
33(6):1359–1378.
Author  Craig A. Thompson

Canine and Feline, Seventh Edition  451
EEosinophilic Granuloma Complex
  BASICS
• Cats—also called feline eosinophilic skin 
disease; term used for three distinct syndromes: 
eosinophilic plaque, eosinophilic granuloma, 
and indolent ulcer; grouped primarily 
according to their clinical similarities, their 
frequent concurrent (and recurrent) develop­
ment, and their positive response to 
corticosteroids; reaction pattern and not a final 
diagnosis unless idiopathic. • Dogs—
eosinophilic granuloma in dogs (EGD) rare; 
specific differences from cats listed separately.
• Eosinophil—major infiltrative cell for 
eosinophilic granuloma and eosinophilic 
plaque, but not typically with indolent ulcer; 
most often associated with allergic or parasitic 
conditions but has a more general role in 
inflammatory reactions. • Eosinophilic 
granuloma complex (EGC)—most often in 
cats with hypersensitivities to inhaled allergens, 
food, or insects, but can also be idiopathic with 
possible genetic causes. • EGD—may have 
both a genetic predisposition and a hyper­
sensitivity cause (especially in non ­genetically 
susceptible breeds).
GENETICS
• Related individuals with disease 
development in a colony of specific 
pathogen ­free cats indicate that genetic 
predisposition (possible inheritable 
dysfunction of eosinophilic regulation) may 
be significant component for development. 
• Genetically predisposed development of 
Seasonal incidence in some geographic 
locations—insect or environmental allergen 
exposure.
Species
• Cats—eosinophilic granuloma, eosinophilic 
plaque, indolent ulcer. • Dogs—eosinophilic 
• Cats—none. • Dogs—EGD: Siberian 
husky (76% of cases), cavalier King Charles 
spaniel.
• Eosinophilic granuloma and plaque—younger 
cats. • Spontaneously regressing eosinophilic 
granuloma— <1 year. • Indolent ulcer—any age. 
• EGD— usually <3 years of age (80%).
• Cats (eosinophilic granuloma, indolent 
ulcer)—predilection for females reported; eosinophilic plaque: no sex predilection. 
• EGD—males (72% of cases).
SIGNS
General Comments—Cats
• Distinguishing among the syndromes 
depends on clinical signs. • Lesions of more 
than one syndrome may occur simultaneously 
or may change over time.
Historical Findings—Cats
• Lesions may develop spontaneously and 
acutely. • Eosinophilic granuloma—variable 
but typically nonpruritic. • Eosinophilic 
plaque—severe pruritus. • Indolent ulcer—
pain and pruritus rare. • Seasonal incidence 
possible (related to insects and allergy). 
• Waxing and waning of clinical signs 
common in all syndromes.
• Eosinophilic plaque —single or multiple, 
alopecic, erythematous, eroded/ulcerated 
well­demarcated and flat ­topped ± white 
necrotic foci; most commonly seen on the 
abdomen and medial thighs, but may also see in 
mucocutaneous junctions and other areas of the 
skin; frequently moist or glistening; may appear 
oval or linear due to pattern of licking. 
• Eosinophilic granuloma —caudal thigh (linear 
granuloma)—distinctly linear orientation on the 
caudal thigh; chin (“pouting cats”)—lip margin 
and chin swelling; paw pads—footpad swelling, 
pain, and lameness; oral cavity—ulceration 
common (especially on the tongue, palate): cats 
with oral lesions may be dysphagic, have 
halitosis, and may drool; can be located 
anywhere on the body; spontaneous regression—
especially in young cats with the inheritable 
form. • Indolent ulcer —classically concave and 
indurated ulcerations with a granular, orange ­
yellow color, confined to the upper lips near 
philtrum or upper canine teeth. • Peripheral 
lymphadenopathy possible for EGC lesions. 
• EGD —ulcerated plaques and nodules; green/
orange color; most often affects the tongue and 
palatine arches; uncommon cutaneous lesions on 
the abdomen, cheek, digits, prepuce, and flanks. 
• Cavalier King Charles spaniels—lesions on the 
soft palate or near the tonsils.
CAUSES
• Hypersensitivity—flea or insect (mosquito 
bite), food hypersensitivity, and atopy; a 
heritable dysfunction has been proposed.
• Idiopathic. • EGD—unknown; genetics in 
susceptible breeds; a hypersensitivity reaction 
often suspected (insect bite) in non ­geneti­
cally susceptible breeds.
  DIAGNOSIS
• Herpes virus dermatitis. • Feline 
leukemia virus (FeLV) or feline immuno­deficiency virus (FIV). • Unresponsive 
lesions—pemphigus foliaceus, 
dermatophytosis and deep fungal infection, 
demodicosis, pyoderma, and neoplasia 
(metastatic adenocarcinoma, squamous cell 
carcinoma, and lymphoma). • EGD—
neoplasia, infectious and noninfectious 
CBC—mild to moderate eosinophilia.
FeLV and FIV.
• Impression smears (cytology) from lesions—
large numbers of eosinophils (indolent ulcer 
may be more neutrophilic). • Comprehensive 
flea and insect control—assist in excluding flea 
or mosquito bite hypersensitivity. • Food 
elimination trial and provocation—appropriate 
in all cases. • Atopy—intradermal skin testing 
(preferred) or serum allergy testing followed by 
immunotherapy. • Biopsy.
• Histopathologic diagnosis—mainly to rule 
out other differentials. • Eosinophilic 
granuloma—nodular to diffuse granulo­
matous dermatitis with flame figures, 
eosinophils, multinucleated histiocytic giant 
cells; mucinosis of epidermis/hair follicle 
outer root sheath, mural eosinophilic 
folliculitis/furunculosis, eosinophilic 
panniculitis possible. • Eosinophilic 
plaque—superficial to deep perivascular 
dermatitis with eosinophilia to interstitial to 
diffuse eosinophilia; mucinosis of epidermis/
hair follicle outer root sheath, diffuse 
spongiosis of outer root sheath, eosinophilic 
microvesicles/microabscesses possible. 
• Indolent ulcer—variable; may be predomin  ­ 
antly neutrophilic or eosinophilic. • EGD—
foci of palisading granulomas and flame 
figures; infiltrate with eosinophils mixed with 
macrophages.
  TREATMENT
• Most patients treated as outpatients unless 
severe oral disease prevents adequate fluid 
intake. • Identify and eliminate offending 
allergen(s) before providing medical inter  ­ 
vention. • Atopy—immunotherapy: 
successful in a majority of cases; preferable to 
long­term corticosteroid administration.
Discourage patient from damaging lesions by 
DIET
No restrictions unless a food allergy is 
suspected. Elimination diet for suspected 
food allergy.

452  Blackwell’s Five-Minute Veterinary Consult  
ECLIENT EDUCATION
• Inform clients about the possible allergic or 
heritable causes. • Discuss the waxing and 
waning nature of these diseases.
EGD—individual lesions may be excised/
removed by carbon dioxide laser if being 
mechanically traumatized and medically 
unresponsive.
• Cases may improve with antibiotics—
amoxicillin trihydrate–clavulanate 10–20 mg/
kg q12h; cefovecin 8 mg/kg every 14 days; or 
clindamycin 11–22 mg/kg q24h. • Oral 
corticosteroids—ongoing treatment necessary 
unless the primary cause is controlled; 
prednisolone 2–4 mg/kg q24h, then as 
required to control lesions; steroid tachy­
phylaxis may occur and may be specific to the 
drug administered; may be useful to change 
the form; other drugs: methylprednisolone 
2–3 mg/kg q24h, dexamethasone 0.1–
0.2 mg/kg q24–72h, and triamcinolone 
0.2–0.3 mg/kg q24–72h; higher induction 
dosages may be required but should be 
tapered as quickly as possible. • Cyclosporine 
modified, 7 mg/kg q24–48h. • Topical—
fluocinolone/dimethyl sulfoxide (DMSO; 
Synotic® lotion) to individual lesions; not 
practical and/or may cause systemic effects in 
patients with large numbers of lesions.
Alternate Therapies
• Chlorambucil 0.1–0.2 mg/kg q24–72h. 
• α­interferon 300–1000 IU/day; limited 
success. • Megestrol acetate—significant side 
effects (e.g., diabetes, mammary cancer, 
pyometra); use not recommended except in 
severe, recalcitrant cases.
EGD
• Oral prednisolone 0.5–2.2 mg/kg/day 
initially; then taper gradually. • Some may 
undergo spontaneous remission.  FOLLOW-UP
• Corticosteroids—baseline and frequent 
hemograms, serum chemistry profiles, and 
urinalyses with culture; excessive or too ­
frequent use of corticosteroids increases risk 
for development of diabetes mellitus and 
acquired skin fragility. • Cyclosporine—
baseline and frequent hemograms, serum 
chemistry profiles, and urinalyses with 
culture; measurement of plasma cyclosporine 
levels as needed to establish dosage within 
therapeutic levels (especially cats); avoid raw 
meat and keep cats indoors. • Selective 
immunosuppressant drugs—frequent 
hemograms (biweekly at first, then monthly 
or bimonthly as therapy continues) to 
monitor for bone marrow suppression; 
routine serum chemistry profiles and 
urinalyses with culture (monthly at first, then 
every 3 months) to monitor for complications 
(renal disease, diabetes mellitus, and urinary 
tract infection).
• Lesions should resolve permanently if a 
primary cause can be identified and 
controlled. • Most lesions wax and wane, 
with or without therapy; an unpredictable 
schedule of recurrence should be anticipated. 
• Drug dosages should be tapered to the 
lowest possible level (or discontinued, if 
possible) once the lesions have resolved. 
• Lesions in cats with the inheritable disease 
may resolve spontaneously after several years.  
• EGD—lesions may be recalcitrant to 
medical intervention.
Systemic glucocorticoids and immuno­
suppressive drugs should not be used during 
pregnancy.SYNONYMS
• Eosinophilic granuloma—feline collagenolytic 
granuloma; feline linear granuloma. • Indolent 
ulcer—eosinophilic ulcer; rodent ulcer; feline 
upper lip ulcerative dermatitis.
SEE ALSO
• Food Reactions, Dermatologic.
• DMSO = dimethyl sulfoxide.
• EGC = eosinophilic granuloma complex.
• EGD = eosinophilic granulomas in dogs.
Buckley L, Nuttall, T. Feline eosinophilic 
granuloma complex(ities): some clinical 
clarification. J Feline Med Surg 2012, 
14:471–481.
King S, Favrot C, Messinger L, et al. A 
randomized double ­blinded placebo ­ 
controlled study to evaluate an effective 
ciclosporin dose for the treatment of feline 
hypersensitivity dermatitis. Vet Derm 2012, 
23:440–e84.
Knight EC, Shipstone MA. Canine eosino­
philic granuloma of the digits treated with 
prednisolone and chlorambucil. Vet Derm 
2016, 27:446–e119.
Miller WH, Griffin CE, Campbell KL. Muller 
& Kirk’s Small Animal Dermatology, 7th ed. 
St. Louis, MO: Elsevier Mosby, 2013.
Rosenkrantz WS. Feline eosinophilic 
granuloma complex. In: Griffin CE, 
Kwochka KW, MacDonald JM, eds., 
Current Veterinary Dermatology: The 
Science and Art of Therapy. St. Louis, MO: 
Mosby, 1993, p. 319.
Resnick
available onlineEosinophilic Granuloma Complex  (continued)

Canine and Feline, Seventh Edition  453
EEpididymitis/Orchitis
  BASICS
OVERVIEW
• Epididymitis—inflammation of an 
epididymis; a prominent clinical sign of 
brucellosis. • Orchitis—inflammation of 
testis; may be concurrent with epididymitis 
(orchiepididymitis). • May be acute or 
chronic.
• Often unilateral. • Infrequent in dogs; rare 
in cats. • No genetic basis or breed predilec­
tions. • Mean age 3.7 years; range: 11 
months–10 years.
SIGNS
• Swollen testis. • Pain (if acute). • Pyrexia. 
• Infertility. • Anorexia. • Listlessness. 
• Reluctance to walk. • Reluctance to breed. 
• Scrotal wound or abscess. • Scrotal 
dermatitis (from licking behavior).
• Infectious— Brucella canis  (brucellosis), 
canine distemper virus, Rickettsia rickettsii  
(Rocky Mountain spotted fever). • Urethritis, 
prostatitis, cystitis. • Blunt abdominal or 
scrotal trauma, including scrotal bite or 
puncture wounds. • Auto ­immune response 
to spermatozoa antigens—secondary to 
trauma or inflammation. • Lymphoplasmacytic 
auto­immune orchitis with, or without, 
thyroiditis.
  DIAGNOSIS
• Inguinoscrotal hernia. • Scrotal dermatitis. 
• Torsion of the spermatic cord. • Hydrocele. 
• Sperm granuloma. • Testicular neoplasia.  
• Prostatitis. • Cystitis.
• Leukocytosis—may be found with acute or 
infectious orchitis. • Pyuria, hematuria, 
proteinuria—may be found if epididymitis/
orchitis is secondary to prostatitis or cystitis.
• Serology—tests identifying B. canis  
antibodies or antigens may take up to 12 
weeks to become detectable: perform 
immediate testing in any dog with scrotal 
enlargement (see Brucellosis). • Rapid slide 
agglutination test (RSAT)—screening test; 
sensitive but not specific. • Due to occurrence 
of false positives with RSAT, retest all 
positives for B. canis  with a more specific test 
method: modified rapid slide agglutination 
test (ME ­RSAT), agar gel immunodiffusion 
test (AGID), tube agglutination test (TAT), 
PCR, or bacterial culture of whole blood or 
lymph node aspirate.IMAGING
• Ultrasonographic evaluation of testes and 
epididymides—inflamed testes have patchy 
hypoechoic areas; inflamed epididymides 
have irregular contours and hypoechoic or 
hyperechoic areas; obtain measurements for 
future comparisons. • Ultrasonographic 
evaluation of prostate to identify underlying 
causes (i.e., prostatitis).
• Bacterial culture of semen (differentiate 
results from normal flora). • Semen cytologic 
evaluation—leukocytes; bacteria; spermatozoa 
with morphologic abnormalities; head ­to­
head agglutination ( B. canis ). • Prostate fluid 
cytologic examination and bacterial culture; 
sample collected aseptically by performing 
prostatic massage (per rectum) after urethral 
catheter placed where tip can be palpated (per 
rectum), followed with 5 mL saline infusion 
and aspiration. • Open wounds—bacterial 
culture. • Fine ­needle aspirate—sample 
enlarged testes/epididymides for cytology and 
culture; leukocytes vary from numerous 
neutrophils (suppurative) to minimal 
inflammatory cells (granulomatous).
  TREATMENT
• Castration—if fertility is not a priority; 
before castration, culture appropriate 
specimen; administer antibiotics perioperat­
ively to avoid scirrhous cord.  • Unilateral 
castration—for unilateral orchitis when 
patient’s fertility must be maintained; 
administer appropriate perioperative 
• If B. canis  is diagnosed, removal of affected 
testicle(s) is strongly recommended due to 
zoonotic potential. • If infection present, 
antibiotic choice should be based on culture 
and sensitivity if available; broad ­spectrum 
antibiotics (e.g., ampicillin sulbactam 
22–30 mg/kg IV q8h) may be administered 
until cultures are available. • If attempting to 
treat B. canis , combined antibiotic regimes 
generally more successful; treatments may fail 
to completely clear infection. • Reported 
success with doxycycline (10 mg/kg PO 
q12h), gentamicin (5 mg/kg SC q24h for 7 
days and repeated every 3 weeks), rifampin 
(5 mg/kg PO q24h), or enrofloxacin (5 mg/
kg PO q12h) for 1–3 months.
• Prognosis for fertility—guarded to poor, 
especially with bilateral orchitis. • Testicular 
degeneration of remaining contralateral testis 
may occur due to elevated intrascrotal 
temperature (inflammation), even following 
unilateral castration. • T rauma or inflammation 
can cause obstruction of efferent tubules or 
epididymal duct, leading to spermatocele or 
sperm granuloma. • Semen—evaluate 
characteristics 3 months after treatment for 
orchitis is completed (dogs).
SEE ALSO
• Brucellosis
• Torsion of thr Spermatic Cord
• ME­RSAT = modified rapid slide 
• RSAT = rapid slide agglutination test.
• TAT = tube agglutination test.
Hollett RB. Canine brucellosis: outbreaks and 
compliance. Theriogenology 2006, 
66(3):575–587.
Disorders of the canine testes and epididy­
mides. In: Johnston SD, Kustritz MVR, 
Olson PN, eds., Canine and Feline 
Theriogenology. Philadelphia, OA: 
Saunders, 2001, pp. 313–317.
Kauffman LK, Petersen CA. Canine brucellosis: 
old foe and reemerging scourge. Vet Clin North 
Am Small Anim Pract 2019, 49(4):763–779.
Carlos R.F . Pinto.

E
454  Blackwell’s Five-Minute Veterinary Consult  
EEpilepsy, Genetic (Idiopathic)—Dogs
  BASICS
Syndrome that is only epilepsy, with no 
demonstrable underlying brain lesion or other 
neurologic signs or symptoms; age-related; 
assumed genetic. The term “idiopathic” 
replaced by “genetic” according to the 
International League Against Epilepsy (ILAE) 
classification (see Appendix IX).
• Exact mechanism unknown. • Likely 
different mechanisms between breeds.
Nervous
GENETICS
Genetic basis suspected in Australian shepherd, 
beagle, Belgian shepherd (Groenendael and 
Tervuren), Bernese mountain dog, border 
collie, dachshund, English springer spaniel, 
Finnish spitz, German shepherd, golden 
retriever, keeshond, Irish wolfhound, Italian 
spinone, Labrador retriever, Shetland 
sheepdog, standard poodle, vizsla.
 0.5–2.3% of all dogs.
Widespread
Species
Dog
Beagles; all shepherds (German, Australian, 
Belgian); Bernese mountain dogs; boxers; 
cocker spaniels; border collies; dachshunds; 
golden retrievers; Irish setters; Labrador 
retrievers; poodles (all sizes); Saint Bernards; 
Shetland sheepdogs; Siberian huskies; 
springer spaniels; Welsh corgis; wirehaired fox 
terriers. Can occur in any breed.
• Mean age 10 months–3 years. • Range 6 
months–5 years.
Male predisposition in Bernese mountain dog.
SIGNS
• Seizures may be generalized (convulsive) 
from onset, or have a short aura (focal onset) 
with rapid secondary generalization. • An 
aura (animal appears frightened, dazed, seeks 
attention, or hides, etc.) frequently precedes 
the generalized seizure. • Focal seizures 
reported in the border collie, Finnish spitz, 
English springer spaniel, Labrador retriever, 
viszla, Belgian shepherd, standard poodle.
• First seizure—between 6 months and 5 
years. • Seizures—often when patient is resting or asleep; often at night or early morning; 
frequency tends to increase if left untreated; 
affected animal falls on its side, becomes stiff, 
chomps its jaw, salivates profusely, urinates, 
defecates, vocalizes, and paddles with all limbs 
in varying combinations; short duration 
(30–90 seconds). • Postictal behavior—
confusion, disorientation; aimless, compulsive, 
blind, pacing; frequent polydipsia and 
polyphagia; recovery immediate or may take 
up to 24 hours. • Dogs with established 
epilepsy might have clustered generalized 
seizures at intervals of 1–4 weeks. • No 
asymmetry should be observed during seizure, 
e.g., twitching more pronounced on one side, 
limb contractions on one side, compulsive 
circling just prior to or after the seizure. 
• Stimulus-induced seizures—seizures only 
upon specific stimulus (sound, event).
• Patients often have recovered at time of 
presentation. • Patients may have postictal 
behavior.
CAUSES
Genetic in some breeds; of unknown cause in 
others.
Known epilepsy in the family line.
  DIAGNOSIS
• Seizure pattern (breed, age at onset, type and 
frequency of seizures)—most important factor 
toward diagnosis. • Acute onset of cluster 
seizures or status epilepticus—rule out toxicity 
or structural brain disease. • >2 seizures within 
the first week of onset—consider diagnosis 
other than genetic epilepsy. • Seizures at <6 
months or >5 years of age—consider metabolic 
or intracranial structural disease; rule out 
hypoglycemia in older dogs. • Focal seizures or 
presence of neurologic deficits—rule out 
intracranial structural disease.
• Usually normal. • Perform before initiating 
drug therapy as baseline data.
Bile acids to rule out hepatic encephalopathy 
unnecessary in dogs with seizures without 
accompanying episodic abnormal behavior.
IMAGING
MRI—if seizure pattern does not fit genetic 
(idiopathic) epilepsy, neurologic deficits are 
present, or intracranial structural disease is 
• Cerebrospinal fluid (CSF)—for suspected 
structural intracranial diseases. 
• Electroencephalography—may see interictal 
spikes, polyspikes, and spike slow wave 
complexes.PATHOLOGIC FINDINGS
• No primary lesion. • Secondary neuronal 
loss and gliosis from prolonged seizures.
  TREATMENT
• Outpatient—recurrence of isolated seizures. 
• Inpatient—for cluster seizures ( >1 seizure 
q24h) or status epilepticus.
Inpatients with seizure disorders require 
constant monitoring.
DIET
• Dogs on chronic phenobarbital (PB) and 
potassium bromide (KBr) treatment often 
become overweight; weight-reducing program 
as necessary. • KBr treatment—insure steady 
levels of salt in diet; increase in salt causes 
increase in bromide excretion preferentially 
over chloride, with subsequent decreased 
serum KBr levels; alternatively, decreased salt 
content increases KBr serum level. • T rial 
with high-fat, low-carbohydrate diet—no 
improvement in seizure control.
• Severe cluster seizures and status epilepticus 
are life-threatening emergencies requiring 
immediate medical attention. • Keep seizure 
calendar noting date, time, length, and 
severity of seizures to assess response to 
treatment. • Once treatment instituted, 
medication is lifelong in most cases. • Abrupt 
drug withdrawal may cause seizures.
• Initiate treatment at second generalized 
seizure if dog <2 years; when interictal period 
gradually shortens in others. • Antiepileptic 
treatment—decreases frequency, severity, and 
length of seizures; perfect control rarely 
achieved. • Tolerance and refractoriness to 
treatment may develop.
Phenobarbital
• Most efficacious antiepileptic drug (AED) 
in the dog. • T raditional first-line drug; initial 
dosage 3–5 mg/kg PO q12h; steady state 
reached at 12–15 days, but levels decrease 
significantly in first 6 months owing to 
activation of lysosomal enzymes. • Optimal 
therapeutic serum levels—100–120  μmol/L or 
23–28  μg/mL. • Oral loading dose (if 
needed)—6–10 mg/kg PO q12h for 2–3 days 
to reach therapeutic range rapidly.
Zonisamide
First-line drug when seizure frequency allows 
(<1/week); 5 mg/kg PO q12h; 10 mg/kg PO 
q12h as add-on to PB; half-life 15 hours;

Canine and Feline, Seventh Edition  455
E
Esteady state 4 days; therapeutic range in 
human 10–45  μg/mL.
Levetiracetam
First-line drug when seizures have focal onset; 
<1 seizure/week; 20–70 mg/kg (smaller 
breeds require higher dosage) PO q8h; must 
be given q8h to reach adequate levels; no 
hepatic metabolism; safe; steady state 3 days; 
therapeutic range in human 10–40  μg/mL.
Potassium Bromide
• T raditional first-line drug; initial dosage 
30 mg/kg PO q24h or divided q12h; half-life 
24–46 days; steady state 3–4 months; varies 
with salt concentration in diet; bioavailability 
differs between dogs. • Optimal therapeutic 
serum levels—20–25 mmol/L or 1.6–2 mg/
mL; if sole antiepileptic drug, 25–32 mmol/L 
or 2–2.25 mg/mL can be safely used. • Add 
on to PB if seizures uncontrolled with 
optimal PB level—beneficial and synergistic 
effect. • Loading dose—may cause vomiting, 
diarrhea, profound longstanding sedation; if 
needed, double daily PO doses for 2 weeks. 
• Renal insufficiency decreases bromide 
elimination; half initial dosage.
Diazepam (At-Home Use)
• To abort ongoing seizures—dogs with cluster 
seizures or status epilepticus. • Insert 0.5–1 mg/kg 
injectable drug in rectum (or intranasal) via 1 
inch teat cannula as soon as a seizure occurs; 
repeat 20 and 40 minutes later for a total of 3 
insertions within 40 minutes; can be safely 
repeated once more in 24h period. • Given 
early in course of ongoing seizures, helps abort 
subsequent seizures. •  Intransal midazolam can 
also be used 0.5 mg/kg. Can be repeated once 
after 20 minutes.
Aminophylline, theophylline.
α-adrenergic agonists (e.g., phenylpropanola-
mine)—CNS excitation.
• Cimetidine and chloramphenicol—interfere 
with PB metabolism; may cause toxic PB levels. 
• PB lowers serum levels of zonisamide and 
levetiracetam. • PB may lower T4 and cause 
upward trend in thyroid-stimulating hormore 
(TSH) without signs of hypothyroidism. • PB 
does not interfere with low-dose 
dexamethasone suppression tests regardless of 
dose and treatment. • Zonisamide decreases 
total T4. • Whenever animals on lifetime 
medication, refer to manufacturer’s drug profile 
or to pharmacist for interaction information.
• With polypharmacy, initiate add-on 
gradually to avoid sedation. • Gabapentin 
10–20 mg/kg PO q8h; low efficacy as 
add-on; newer analog pregabalin may be 
more efficacious, 2–4 mg/kg q8h PO. 
• Clorazepate 0.5–1 mg/kg PO q8h. 
• Felbamate 30–70 mg/kg q12h–8h. 
• Topiramate 2–10 mg/kg PO q12h. • Phenytoin, valproic acid, carbamazepine, 
and ethosuximide—unsuitable pharmaco -
kinetics in dogs. • Others—acupuncture, 
vagal nerve stimulation, transcranial magnetic 
motor stimulation. • CBD-infused oil 2.5 
mg/kg (1.1 mg/lb) q12h.
  FOLLOW-UP
• Serum drug levels—preferentially at trough, 
at same time for each sampling; use same 
laboratory. • Phenobarbital—measure PB 
level 4 weeks after initiating therapy; adjust 
dose as needed; then repeat level every 2 
weeks until optimal levels reached; with 
chronic use perform CBC, biochemistry, and 
PB level every 6–12 months; tabulate 
albumin, liver enzymes, and serum drug levels 
to monitor trend; drug essentially hepatotoxic; 
most dogs eventually develop hepatotoxicity 
if serum levels >140 μmol/L ( >33 μg/mL) for 
long time ( >6–8 months); if hepatotoxicity 
suspected, perform bile acids. • KBr—serum 
level (along with PB level) 4–6 weeks after 
initiating (should be 8–12 mmol/L or 
0.5–1 mg/mL) and at 3–4 months; if diet 
change required, consider diet salt content; 
monitor level accordingly; monitor KBr level 
closely if renal insufficiency (isosthenuria or 
azotemia). • Zonisamide—measure level at 1 
week; monitor electrolytes and acid-base 
status to check for renal tubular acidosis. 
• Levetiracetam—measure level at 4 days.
• Abrupt discontinuation of medication may 
precipitate seizures. • Avoid salty treats in 
dogs treated with KBr.
• Recurrent episodes of cluster seizures and 
status epilepticus. • PB and KBr—polyuria, 
polydipsia, polyphagia, weight gain. 
• Phenobarbital-induced corticosteroid 
alkaline phosphatase (C-AP) elevation occurs 
frequently; may be early sign of hepatotoxicity, 
but of less concern if alanine aminotransferase 
(ALT) is within reference range. • PB-induced 
hepatotoxicity—after chronic treatment at 
high serum levels ( >140 μmol/L or >33 μg/
mL); often insidious in onset; only biochemical 
abnormality may be decreased albumin. 
• Higher incidence of pancreatitis in patients 
treated with PB and/or KBr; once pancreatitis 
develops, recurrence is frequent. 
• Phenobarbital—rare bone marrow suppression 
with severe neutropenia (± sepsis) early in 
course of treatment; discontinue drug. 
• Paradoxical hyperexcitability; discontinue 
drug; risk factor for superficial necrolytic 
dermatitis. • KBr—when levels are >22 mmol/L 
or >1.8 mg/mL, owners may complain of 
patient’s unsteadiness while managing stairs. 
• Zonisamide—mild sedation, decreased 
appetite, gastrointestinal signs. • One case of renal tubular acidosis and one case of acute 
idiosyncratic hepatic necrosis reported. 
• Levetiracetam—transient sedation.
• T reatment for life. • Some dogs are well 
controlled with same drug and dosage for 
years; others remain poorly controlled despite 
polypharmacy. • Patient may develop status 
epilepticus and die. • Early treatment does 
not decrease occurrence of status epilepticus. 
• Normal expected lifespan, but survival time 
shorter if episodes of status epilepticus. 
• T reatment with 2 AEDs not linked to poor 
prognosis. • Increased risk of premature 
death. • Marked breed differences in 
incidence and mortality rates. • Prognosis 
depends on combined veterinary expertise, 
therapeutic success, and owner’s motivation.
Idiopathic epilepsy can be a reason for 
euthyroid sick syndrome in dogs.
If onset <2 years of age, epilepsy more likely 
to be difficult to control; condition may 
become intractable.
• Avoid breeding affected animals. • Reported 
association between estrus and onset of 
seizures in intact bitches with presumptive 
“idiopathic” epilepsy; two hormonally based 
patterns recognized: during heat; and during 
a specific time point at the end of diestrus.
SEE ALSO
Cats. • Seizures (Convulsions, Status 
epilepticus)—Dogs.
• AED = antiepileptic drug.
• ALT = alanine aminotransferase. • C-AP = 
corticosteroid alkaline phosphatase. • CSF = 
cerebrospinal fluid. • ILAE = International 
League Against Epilepsy. • KBr = potassium 
bromide. • PB = phenobarbital. • TSH = 
thyroid-stimulating hormone.
http://www.canine-epilepsy.net
Muñana KR. Management of refractory epilepsy. 
Top Companion Anim Med 2013, 28:67–71.
Podell M. Antiepileptic drug therapy and 
monitoring. Top Companion Anim Med 
2013, 28:59–66.
available online(continued)  Epilepsy, Genetic (Idiopathic)—Dogs

456  Blackwell’s Five-Minute Veterinary Consult  
EEpiphora
  BASICS
Abnormal overflow of the aqueous portion of 
the precorneal tear film.
Caused by one of three common problems: 
overproduction of the aqueous portion of tears 
(usually in response to ocular irritation); poor 
eyelid function secondary to eyelid malforma -
tion, breed conformation, or deformity; or 
blockage of the nasolacrimal drainage system.
Eye and periocular skin.
Dogs and (less frequently) cats. See Causes.
SIGNS
N/A
CAUSES
Overproduction of Tears Secondary 
to Ocular Irritants
• Distichiasis or trichiasis—common in 
young Shetland sheepdogs, shih tzus, Lhasa 
apsos, cocker spaniels, miniature poodles.
• Entropion—Chinese Shar-Peis, chow 
chows, Labrador retrievers.
• Eyelid agenesis—domestic shorthair cats.
Acquired
• Corneal or conjunctival foreign bodies—
usually young, large-breed, active, outdoor 
dogs.
• Eyelid neoplasms—old dogs (all breeds).
• Blepharitis—infectious or immune 
mediated.
• Conjunctivitis—infectious or immune 
mediated.
• Ulcerative keratitis (traumatic or viral).
• Anterior uveitis.
Eyelid Abnormalities or Poor Eyelid 
Function
• Abnormal eyelid function does not direct 
tears toward the medial canthus and naso  - 
lacrimal puncta.
• Tears never reach the nasolacrimal puncta 
and subsequently spill over the eyelid margin.
• Macropalpebral fissures—brachycephalic 
breeds.
• Ectropion—Great Danes; bloodhounds; 
spaniels.
• Entropion—brachycephalic dogs: medial 
lower eyelid; Labrador retrievers: lateral lower 
eyelid.
Acquired
• Post-traumatic eyelid scarring.
• Facial nerve paralysis.Obstruction of the Nasolacrimal 
Drainage System
• Imperforate nasolacrimal puncta—Bedlington 
terriers, cocker spaniels, bulldogs, poodles.
• Ectopic nasolacrimal openings—extra 
openings along the side of the face ventral to 
• Nasolacrimal atresia—lack of distal 
openings into the nose.
• Punctal displacement.
• Lack of ventral canaliculus, nasolacrimal 
sac, or nasolacrimal duct.
Acquired
• Rhinitis or sinusitis—causes swelling 
adjacent to the nasolacrimal duct.
• T rauma—resulting in fractures of the 
lacrimal or maxillary bones or laceration of 
the nasolacrimal duct.
• Foreign bodies—grass awns, seeds, sand, 
• Neoplasia—of third eyelid, conjunctiva, 
medial eyelids, nasal cavity, maxillary bone, or 
periocular sinuses causing invasion or 
compression of the nasolacrimal system.
• Dacryocystitis—inflammation of canaliculi, 
lacrimal sac, or nasolacrimal ducts.
• Breeds prone to congenital eyelid abnormalities 
• Active outdoor dogs—at risk for foreign 
bodies.
  DIAGNOSIS
• Other ocular discharges (e.g., mucous or 
purulent)—epiphora is a watery, serous 
discharge.
• Primary ocular abnormalities—usually the 
eye is red when the epiphora is caused by 
overproduction and quiet when secondary to 
impaired outflow.
• Irritative causes and some congenital causes 
of obstruction—thorough ocular examination.
• Acute onset, unilateral condition with 
ocular pain (blepharospasm)—usually 
indicates a foreign body or corneal injury.
• Chronic, bilateral condition—usually 
indicates a congenital problem.
• Facial pain, swelling, nasal discharge, or 
sneezing—may indicate nasal or sinus infection; 
may indicate obstruction from neoplasm.
• With mucous or purulent discharge at 
the medial canthus—may indicate 
dacryocystitis.
N/A
• Skull radiographs—may show a nasal, 
sinus, or maxillary bone lesion.
• Dacryocystorhinography—radiopaque 
contrast material to help localize obstruction.
• MRI or CT—may help localize obstruction 
(usually with contrast media) and characterize 
associated lesions.
• Bacterial culture and sensitivity testing and 
cytologic examination of purulent material from 
the puncta (e.g., dacryocystitis); performed 
before instilling any substance into the eye.
• Jones test—topical fluorescein dye 
application to the eye; most physiologic test 
for nasolacrimal function; should be 
performed first (after culture); dye flows 
through the nasolacrimal system and reaches 
the external nares in approximately 10 
seconds (or longer) in normal dogs, 15 
seconds to 1 minute in cats.
• Nasolacrimal irrigation—see below.
• Rhinoscopy—with or without biopsy or 
bacterial culture; may be indicated if previous 
tests suggest a nasal or sinus lesion.
• Exploratory surgery—may be the only way 
to obtain a definitive diagnosis.
• Temporary tacking out of the lower medial 
eyelid with suture—may help determine 
whether repair of medial lower entropion or 
repositioning of the eyelid would reduce 
epiphora secondary to eyelid conformational 
Nasolacrimal Irrigation
• Confirms obstruction.
• May dislodge foreign material.
• A nasolacrimal cannula or 22- or 24-gauge 
IV catheter without stylet is inserted into the 
upper nasolacrimal punctum.
• Eyewash in a 6 ml syringe is attached and 
irrigated through the cannula or catheter—if 
fluid does not exit the lower nasolacrimal 
punctum, the obstruction is in the upper or 
lower canaliculi, the nasolacrimal sac, or the 
lower punctum (imperforate).
• Lower punctum is manually obstructed—if 
flushed fluid does not exit the external nares, 
the obstruction is in the nasolacrimal duct or 
at its distal opening (atresia or blockage from 
a nasal sinus lesion).
  TREATMENT
• Remove cause of ocular irritation—removal 
of a conjunctival or corneal foreign body, 
treatment of the primary ocular disease (e.g., 
conjunctivitis, ulcerative keratitis, and 
uveitis), cryosurgery or electroepilation for 
distichiasis, entropion correction, medial or 
lateral canthoplasty (for medial trichiasis and 
macropalpebral fissures), correction of 
cicatricial eyelid abnormalities.

Canine and Feline, Seventh Edition  457
E• T reat primary obstruction (e.g., third eyelid 
mass, nasal or sinus mass, and infection)— 
successful management may allow normal 
nasolacrimal flow to resume.
• In patients predisposed to nasolacrimal 
obstruction, recurrence is common.
• Inform client that early detection and 
intervention provide better long-term prognosis.
Imperforate Puncta
• Surgical opening of the puncta is indicated.
• If one of the puncta is patent (usually the 
upper punctum), flushing eyewash through 
the upper opening will cause “tenting” of the 
conjunctiva at the site of the lower punctum. 
Place patient under topical or general 
anesthesia. Grasp conjunctiva overlying the 
lower canaliculi with forceps and cut with 
scissors to leave a patent punctum.
• Puncta closed by conjunctival scarring 
(symblepharon) caused by severe conjunctivi-
tis (e.g., herpesvirus conjunctivitis in cats)— 
use same procedure.
• Recurrent disease—may be necessary to 
suture Silastic® tubing in place to prevent 
stricture formation.
Obstructed or Obliterated Distal 
Nasolacrimal Duct
• Dacryocystorhinotomy, conjunctivorhinos -
tomy, conjunctival maxiallary sinusostomy, 
conjunctival buccostomy—create an opening to 
drain the tears into the nasal cavity or oral cavity.
• See Suggested Reading for surgical 
• Topical broad-spectrum antibiotic ophthalmic 
solutions—while awaiting results of bacterial 
culture; q4–6h; may try neomycin, gramicidin, 
polymyxin B triple ophthalmic antibiotic 
solution, or ophthalmic ciprofloxacin solution.
• Dacryocystitis—based on bacterial culture 
and sensitivity test results; continue antibiotic 
therapy for at least 21 days.
• Topical corticosteroids or antibiotic–corti-
costeroid combinations—avoid unless a 
definitive diagnosis has been made.
• Topical corticosteroids—never use if the 
cornea retains fluorescein stain (corneal ulcer 
present).PRECAUTIONS
N/A
N/A
  FOLLOW-UP
Dacryocystitis
• Reevaluate every 7 days until the condition 
is resolved.
• Continue treatment for at least 7 days after 
resolution of clinical signs.
• If problem persists more than 7–10 days 
with treatment or recurs soon after 
cessation of treatment—indicates a foreign 
body or nidus of persistent infection; 
requires further diagnostics (e.g., 
dacryocystorhinography).
• Nasolacrimal catheter; commonly required 
for persistent dacryocystitis, maintains 
patency of the duct and prevents stricturing.
• Procedure—pass 2-0 nylon via the upper 
punctum and thread it through the nasolacri-
mal duct to exit the external nares; pass 
Silastic or polyethylene (PE90) tubing 
retrograde over the suture; suture the upper 
and lower portions of the tubing to the face. 
Most dogs tolerate the tubing well; however, 
an Elizabethan collar may be needed to 
prevent self-trauma. Continue topical 
antibiotics as before. Leave in place 2–4 
weeks.
Dacryocystorhinotomy/
Conjunctivorhinostomy
• T ubing—reevaluate every 7 days to ensure 
it remains intact; may need to resuture if it 
becomes loosened or dislodged.
• After tubing has been removed—reevaluate 
in 14 days; for this and future examinations, 
place fluorescein on the eye and check naso  - 
lacrimal patency by examining the external 
nares for fluorescein; may evaluate further by 
cannulating and flushing with eyewash.
• Dacryocystorhinography contrast study—
repeated 3–4 months after surgery to evaluate 
size of nasal opening; repeated for recurrence 
or with no nasolacrimal fluorescein drainage.
Recurrence—most common complication; 
caused by recurrence of ocular irritation 
(e.g., corneal ulceration, distichiasis, 
entropion), recurrence of dacryocystitis, or closure of the dacryocystorhinotomy or 
conjunctivorhinostomy openings into the 
nasal cavity.
• Chronic conjunctivitis.
• Recurrent eye “infections.”
• Moist dermatitis (hot spots) ventral to the 
medial canthus.
• Nasal discharge.
N/A
N/A
N/A
SEE ALSO
• Eyelash Disorders (T richiasis/Distichiasis/
Ectopic Cilia).
• Third Eyelid Protrusion.
Binder DR, Herring IP . Evaluation of 
nasolacrimal fluorescein transit time in 
ophthalmically normal dogs and 
nonbracycephalic cats. Am J Vet Res 2010, 
71:570–574.
Giuliano EA. Diseases and surgery of the 
canine nasolacrimal system. In: Gelatt KN, 
Gilger BC, Kern T, eds., Veterinary 
Wiley-Blackwell, 2013, pp. 912–944.
Miller PE. Lacrimal system. In: Maggs DJ, 
Miller PE, Ofri R, Slatter’s Fundamentals of 
Veterinary Ophthalmology, 6th ed. St. 
Louis, MO: Elsevier, 2018, pp. 186–-203.
Author  Silvia G. Pryor
Brian C. Gilger.
available online(continued)  Epiphora

458  Blackwell’s Five-Minute Veterinary Consult  
EEpiscleritis
  BASICS
OVERVIEW
• Focal or diffuse infiltration of episclera and/
or scleral stroma by inflammatory cells and 
fibroblasts.
• Primary—affects only the eye; probably 
immune mediated; appears either as a 
perilimbal episcleral/scleral nodule (nodular 
episcleritis) or as a diffuse thickening of the 
episclera (diffuse episcleritis); nodular form may 
affect cornea and third eyelid with nodules.
• Secondary—usually diffuse; from spillover 
of inflammatory cells into the episclera from 
other ocular disorders (e.g., endophthalmitis 
and panophthalmitis); may affect virtually 
any other organ system.
• Dog.
• Young to middle-aged collie, Shetland 
sheepdog.
SIGNS
• Nodular—typically appears as a smooth, 
painless, localized, raised, pink-tan, firm 
episcleral/scleral mass.
• Diffuse—less common; appears as a diffuse 
reddening and thickening of the entire 
episclera/sclera; accompanied by variable 
amounts of ocular pain.
• Secondary—uveitis often pronounced.
• Conjunctiva—usually moves freely over the 
surface of the lesion.
• Nodules—tend to be slowly progressive, 
bilateral, and prone to recurrence.
• Nodular and diffuse primary—idiopathic; 
believed to be immune mediated.
• Secondary—may result from deep fungal or 
bacterial ocular infection, lymphoma, 
systemic histiocytosis in Bernese mountain 
dogs, chronic glaucoma, and ocular trauma.
  DIAGNOSIS
• Other causes of a red eye—differentiated by 
complete ophthalmic examination.
• Other mass-like lesions—differentiated by 
biopsy or cytologic examination.
• Neoplasia—lymphoma, squamous cell 
carcinoma, extension of intraocular mass, 
• Granuloma—deep fungal infection, 
retained foreign body.
• Granulation tissue—trauma, healing corneal 
ulcer, globe perforation with uveal prolapse.
• Usually normal if lesion is confined to eye 
or adnexa.• Secondary—may see abnormalities 
consistent with systemic disease.
Serologic testing—may help diagnose fungal 
IMAGING
• Abdominal ultrasound, thoracic and 
abdominal radiographs—may help rule out 
fungal infection or disseminated neoplasia.
• Ocular ultrasound—may reveal other 
abnormalities if ocular media opacities 
prevent thorough ocular examination.
• Incisional biopsy and histopathologic 
examination of affected tissue.
• Nodular—varying numbers of histiocytes, 
lymphocytes, plasma cells, and fibroblasts.
• If uveitis prominent—see Anterior 
Uveitis—Dogs.
  TREATMENT
• Verify the diagnosis histologically or 
cytologically before treatment.
• Primary nodular—benign course; observa-
tion alone may be appropriate with mild 
disease.
• Outpatient treatment if ocular pain, diffuse 
scleral involvement, eyelid function is 
disrupted, cornea is affected, or vision is 
threatened.
• Progress down the list only if the previous 
modality was ineffective.
• Topical 1% prednisolone acetate q4h for 
1 week, then q6h for 2 weeks, then 
tapered.
• Systemic prednisolone 1–2 mg/kg/day PO; 
taper with improvement.
• Systemic azathioprine 1–2 mg/kg/day PO for 
3–7 days; then tapered to as low as possible.
• Cryosurgery or attempted excision.
• Alternative to listed drugs or surgery—may 
try a combination of tetracycline and niacina -
mide (q8h PO); 250 mg each for dogs <10 kg; 
500 mg each for dogs >10 kg; may not observe 
good clinical response for at least 8 weeks; side 
effects uncommon and primarily the result of 
gastrointestinal upset by niacinamide.
• Avoid systemic immunosuppressive drugs 
with fungal infections.
• Systemically administered prednisolone—
may precipitate pancreatitis, iatrogenic 
hyperadrenocorticism.• Azathioprine—may induce potentially fatal 
myelosuppression, hepatotoxicosis.
• Niacin—do not substitute for niacinamide.
  FOLLOW-UP
• Primary—monitor for nodule regression or 
reduction in episcleral thickening or reddening 
every 2–3 weeks for 6–9 weeks and then as 
needed; prognosis usually good; may require 
therapy for months to rest of life.
• Secondary—follow-up, prognosis, and 
complications depend on primary disease.
• Azathioprine—repeat CBC, platelet count, 
and measurement of liver enzymes every 1–2 
weeks for first 8 weeks, then periodically.
• Vision loss.
• Uveitis.
• Secondary glaucoma.
SYNONYMS
• Collie granuloma.
• Fibrous histiocytoma.
• Limbal granuloma.
• Necrogranulomatous sclerouveitis.
• Nodular fasciitis.
• Nodular granulomatous episcleritis.
• Proliferative keratoconjunctivitis.
Maggs DJ. Diseases of the cornea and sclera. 
In: Maggs DJ, Miller PE, Ofri R, Slatter’s 
Elsevier 2018, pp. 213–253.
Rothstein E, Scott DW, Riis RC. Tetracycline 
and niacinamide for the treatment of sterile 
pyogranuloma/granuloma syndrome in a dog. 
J Am Anim Hosp Assoc 1997, 33:540–543.

Canine and Feline, Seventh Edition  459
EEpistaxis
  BASICS
Bleeding from the nose.
Results from one of three abnormalities—
coagulopathy; local disease or space-
occupying lesion; vascular or systemic disease.
• Respiratory—hemorrhage; sneezing
• Gastrointestinal (GI)—melena.
• Hemic/lymphatic/immune—anemia.
GENETICS
Varies depending on underlying cause.
Species
Age, Breed, and Sex Predilections
Vary depending on underlying cause.
SIGNS
• Nasal hemorrhage—unilateral or bilateral 
possible.
• Sneezing and/or stertorous respiration.
• Melena.
• With coagulopathy—hematochezia, 
melena, hematuria, or hemorrhage from other 
areas of the body.
• With hypertension—possibly blindness, 
intraocular hemorrhage, neurologic signs, 
cardiac or renal signs.
• Nasal hemorrhage.
• Melena—from swallowing blood or 
concurrent upper GI hemorrhage.
• Nasal stridor—may be present with 
neoplasia, foreign body, or advanced 
inflammatory disease.
• With coagulopathy—possibly petechiae, 
ecchymosis, hematomas, intracavitary bleeds, 
hematochezia, melena, and hematuria.
• With coagulopathy or hypertension—
possibly retinal or intraocular hemorrhages or 
retinal detachment; with hypertension—
possibly heart murmur or arrhythmia.
CAUSES
Coagulopathy
Thrombocytopenia
• Immune-mediated disease—idiopathic 
disease; drug reaction; modified live virus 
(MLV) vaccine reaction.
• Infectious disease—ehrlichiosis; 
anaplasmosis; Rocky Mountain spotted fever, 
babesiosis, feline leukemia virus (FeLV) or 
feline immunodeficiency virus (FIV)-related 
illness.• Bone marrow disease—neoplasia; aplastic 
anemia; infectious (fungal, rickettsial, or viral).
• Paraneoplastic disorder.
• Disseminated intravascular coagulation 
(DIC).
Thrombopathia
• Congenital—von Willebrand disease; 
thrombasthenia; thrombopathia.
• Acquired—nonsteroidal anti-inflammatory 
drugs (NSAIDs); clopidogrel; hyperglobulinemia 
(Ehrlichia , multiple myeloma); uremia; DIC.
Coagulation Factor Defects
• Congenital—hemophilia A (factor VIIIc 
deficiency) and hemophilia B (factor IX 
• Acquired—anticoagulant rodenticide 
(warfarin) intoxication, hepatobiliary 
disease, DIC.
Local Lesion
• T rauma.
• Infection—fungal ( Aspergillus , Cryptococcus , 
Rhinosporidium ); viral or bacterial. Usually 
blood-tinged mucopurulent exudate rather 
than frank hemorrhage.
• Neoplasia—adenocarcinoma; carcinoma; 
chondrosarcoma; squamous cell carcinoma; 
fibrosarcoma; lymphoma; transmissible 
venereal tumor.
• Dental disease—oronasal fistula, tooth root 
abscess.
Vascular or Systemic Disease
• Hypertension—renal disease; hyperthyroid -
ism; hyperadrenocorticism; pheochromocy-
toma; idiopathic disease.
• Hyperviscosity—hyperglobulinemia 
(multiple myeloma, Ehrlichia ); polycythemia.
• Vasculitis—immune-mediated and rickettsial 
diseases.
• Immune-mediated disease—young to middle-  
aged, small-to medium-sized female dogs.
• Infectious disease—dogs living in or traveling 
to endemic areas; tick exposure.
• Thrombasthenia—otter hounds.
• Thrombopathia—basset hounds, spitz.
• von Willebrand disease—Doberman 
pinschers, Airedales, German shepherds, 
Scottish terriers, Chesapeake Bay retrievers, and 
many other breeds; cats.
• Hemophilia A—German shepherds and 
• Hemophilia B—Cairn terriers, coonhounds, 
Saint Bernards, and other breeds; cats.
Space-Occupying Lesions
• Aspergillosis—German shepherds, 
Rottweilers, mesocephalic and dolichocephalic 
breeds.
• Neoplasia—dolichocephalic breeds.  DIAGNOSIS
• Anemia—if enough hemorrhage has 
occurred.
• Thrombocytopenia—possible.
• Neutrophilia—infection; neoplasia.
• Pancytopenia—if bone marrow disease.
• Hypoproteinemia—if enough hemorrhage 
has occurred.
• High blood urea nitrogen (BUN) with 
normal creatinine—possible, owing to blood 
• Hyperglobulinemia—possible with 
ehrlichiosis, multiple myeloma.
• Azotemia—with renal failure-induced 
• High alanine transaminase (ALT), aspartate 
aminotransferase (AST), and total bilirubin—
with coagulopathy from severe hepatic disease.
• Urinalysis—usually normal; possible to see 
hematuria (if coagulopathy), isosthenuria (if 
renal failure–induced hypertension), and 
proteinuria (if glomerulotubular disease and 
hypertension).
• Coagulation profile—prolonged times with 
coagulation factor defects; normal with 
thrombocytopenia and thrombopathia.
• Platelet function testing (e.g., buccal 
mucosal bleeding time, von Willebrand factor 
analysis)—may be abnormal with platelet 
dysfunction (platelet count and coagulation 
profile may be normal).
• Ehrlichia , Anaplasma , Rocky Mountain 
spotted fever, or Babesia  testing—may be 
positive in thrombocytopenia or thrombo -
pathia-induced epistaxis.
• Aspergillus  serology—may help establish a 
diagnosis of fungal rhinitis; false-negative results 
are common, so results must be interpreted in 
light of other clinical and diagnostic findings.
• Thyroid hormone assay—elevated in cats 
with epistaxis due to hyperthyroid-induced 
IMAGING
• Thoracic radiograph—screen for metastasis.
• Nasal series—under anesthesia, including 
open-mouth ventrodorsal and skyline sinus 
views when space-occupying or local lesion is 
suspected; osteolysis with neoplasia and 
fungal sinusitis; foreign bodies usually not 
seen; dental disease may be identified.
• CT or MRI—more sensitive than 
• Blood pressure evaluation—indicated when 
coagulopathies and space-occupying lesions 
have been ruled out and particularly when 
azotemia or proteinuria is noted.

460  Blackwell’s Five-Minute Veterinary Consult  
E• Rhinoscopy, nasal lavage, nasal biopsy (blind 
or guided via rhinoscopy or CT)—indicated 
for space-occupying disease; aimed at removing 
foreign bodies and evaluating and sampling 
nasal tissue for causal diagnosis (e.g., evaluate 
nasal tissue samples for neoplasia, inflamm -
ation, and infection via cytology and/or 
histopathology and bacterial/fungal culture 
and sensitivity testing).
• Bone marrow aspiration biopsy—indicated if 
pancytopenia identified.
  TREATMENT
• Coagulopathy—usually inpatient 
• Space-occupying lesion or vascular or systemic 
disease—outpatient or inpatient management, 
depending on disease and its severity.
• Nasal tumors—radiotherapy; various 
response rates.
Provide basic supportive care if needed 
(fluids, nutrition).
ACTIVITY
Minimize activity or stimuli that precipitate 
hemorrhage episodes.
• Inform client about the disease process.
• Teach client how to recognize a serious 
hemorrhage (e.g., weakness, collapse, pallor, 
and blood loss >30 mL/kg bodyweight).
• Surgery indicated if a foreign body is unable 
to be removed by rhinoscopy or blind attempt.
• Fungal rhinitis (e.g., Aspergillus  and 
Rhinosporidium ) require debulking (also see 
Medications).
General
• Whole blood, packed red blood cell (RBC), 
or hemoglobin solution transfusion—can be 
needed with severe anemia.
• Acepromazine (0.05–0.1 mg/kg SC/IV if 
normothermic and no platelet disorder present) 
to lower blood pressure and promote clotting; 
may help control serious hemorrhage.
• Discontinue all NSAIDs.
• Immune-mediated thrombocytopenia—
prednisone (1.1 mg/kg q12h; taper over 4–6 
months); other drugs can be used in addition 
to prednisone for refractive cases (see 
Thrombocytopenia, Primary Immune 
Mediated).• Infectious disease—rickettsial disease 
(doxycycline 5 mg/kg PO q12h for 3–6 
weeks); Babesia  (imidocarb 6.6 mg/kg SC 2 
doses 2 weeks apart, diminazene aceturate 
5 mg/kg IM once, or 10 days of atovaquone 
13.3 mg/kg PO q8h with azithromycin 
• Bone marrow neoplasia—see 
Myeloproliferative Disorders.
• Thrombopathia and thrombasthenia—no 
treatment unless lymphoproliferative disease.
• von Willebrand disease—plasma or 
cryoprecipitate for acute bleeding; 1-desamino-
8-d-arginine vasopressin (DDAVP) 1  μg/kg 
SC/IV diluted in 20 mL 0.9% NaCl given over 
10 min may help control or prevent 
hemorrhage prior to invasive procedures; 
intranasal formulation (less expensive) may be 
used after passing through a bacteriostatic filter.
• Hemophilia A—plasma or cryoprecipitate for 
acute bleeding; no long-term treatment.
• Hemophilia B—plasma for acute bleeding; 
no long-term treatment.
• Anticoagulant rodenticide intoxication—
plasma for acute bleeding; vitamin K at 5 mg/
kg loading dose followed by 1.25 mg/kg q12h 
for 1 week (if warfarin formulation) to 4 weeks 
(longer-acting formulation).
• Hyperglobulinemia—plasmapheresis.
• Polycythemia—phlebotomy; hydroxyurea.
• Liver disease and DIC—treat and support 
underlying cause; plasma may be beneficial.
Space-Occupying Lesion
• Secondary bacterial infection—antibiotics 
based on culture and sensitivity testing.
• Fungal infection—for aspergillosis, topical 
treatment of nasal cavity and frontal sinuses 
with 1% clotrimazole in polyethylene glycol 
(see Precautions) or 1–5% enilconazole (see 
Aspergillosis, Nasal for protocol); for 
cryptococcosis—oral and injectable anti -
fungal agents (see Cryptococcosis); for 
rhinosporidiosis—surgery followed by 
dapsone (1 mg/kg PO q8h for 2 weeks, then 
1 mg/kg PO q12h for 4 months).
• Hyperviscosity—treat underlying disease 
(e.g., ehrlichiosis, multiple myeloma, or 
polycythemia); plasmapheresis.
• Vasculitis— doxycycline for rickettsial 
disease (5 mg/kg q12h for 3–6 weeks); 
prednisone for immune-mediated disease 
(1.1 mg/kg q12h; taper over 4–6 months).
Hypertension
• T reat underlying disease—renal disease, 
hyperthyroidism, hyperadrenocorticism.
• Reduce weight if overconditioned.
• Restrict sodium.
• Calcium channel blockers—amlodipine 
(dogs: 0.1 mg/kg PO q12–24h; cats: 
0.625–1.25 mg/cat PO q12–24h); treatment 
of choice.
• ACE inhibitors—benazepril (0.5 mg/kg 
q24h); enalapril (0.25–0.5 mg/kg q12–24h).• Beta blockers—propranolol (0.5–1 mg/kg 
q8h); atenolol (0.25–1.0 mg/kg q12–24h).
• Diuretics—hydrochlorothiazide (2–4 mg/
kg q12h); furosemide (0.5–2 mg/kg q8–12h).
• Phenoxybenzamine (0.2–1.5 mg/kg q12h) 
for pheochromocytoma.
• Avoid drugs that may predispose patient to 
hemorrhage—NSAIDs; heparin; clopidogrel; 
phenothiazine tranquilizers.
• Topical antifungals—do not use in patients 
with disruption of the cribriform plate.
• Chemotherapeutic drugs (immune-
mediated thrombocytopenia therapy, e.g., 
azathioprine)—monitor neutrophil counts 
and liver enzymes weekly until a pattern has 
been established that shows that the patient is 
tolerating the drug.
• Enalapril and/or diuretics—closely monitor 
patients with renal failure; avoid severe salt 
restriction when using angiotensin-converting 
enzyme (ACE) inhibitors.
• Avoid topical clotrimazole preparations 
with propylene glycol, as life-threatening 
mucosal irritation, ulceration, and naso -
pharyngeal swelling can occur.
  FOLLOW-UP
• Platelet count with thrombocytopenia.
• Coagulation profile with coagulation factor 
defects.
• Blood pressure with hypertension.
• Clinical signs.
• Restrict access to areas that might contain 
anticoagulant rodenticides.
• Practice dental preventative care.
Anemia and collapse (rare).
Avoid teratogenic drugs (e.g., itraconazole).
• DDAVP = 1-desamino-8-d-arginine 
vasopressin.
• FIV = feline immunodeficiency virus.Epistaxis  (continued)

Canine and Feline, Seventh Edition  461
E
• MLV = modified live virus.
drug.
Bissett SA, Drobatz KJ, McKnight A, Degernes 
LA. Prevalence, clinical features, and causes of 
epistaxis in dogs: 176 cases (1996–2001). J 
Am Vet Med Assoc 2007, 231:1843–1850.
Brooks MB, Catalfamo JL. Immune-mediated 
thrombocytopenia, von Willebrand disease, and platelet disorders. In: Ettinger SJ, 
Internal Medicine, 7th ed. St. Louis, MO: 
Saunders Elsevier, 2010, pp. 772–783.
Veterinary Internal Medicine, 7th ed. 
St. Louis, MO: Saunders Elsevier, 2010, 
pp. 797–801.
Venker-van Haagen AJ, Herrtage ME. Diseases 
of the nose and nasal sinuses. In: Ettinger SJ, 
Feldman EC, eds., Textbook of Veterinary Internal Medicine, 7th ed. St. Louis, MO: 
Saunders Elsevier, 2010, pp. 1030–1040.
Author  Meghan Vaught
Mitchell A. Crystal.
available online(continued)  Epistaxis

462  Blackwell’s Five-Minute Veterinary Consult  
EErythrocytosis
  BASICS
An increase in packed cell volume (PCV), 
hemoglobin concentration, or red blood cell 
(RBC) count above the reference interval due 
to a relative or absolute increase in the 
number of circulating RBCs.
• Circulating RBC numbers are affected by 
changes in plasma volume, rate of RBC 
destruction or loss, splenic contraction, 
erythropoietin (EPO) secretion, and bone 
marrow production.
• Erythropoiesis is also affected by hormones 
from the adrenal cortex, thyroid gland, ovary, 
testis, and anterior pituitary gland; normal 
PCV is maintained by an endocrine loop.
• Erythrocytosis is either relative or absolute.
• Relative—develops when hemoconcentra-
tion or splenic contraction produces an 
increase in circulating RBCs.
• Absolute—increase in circulating RBC 
mass due to an increase in bone marrow 
production; either primary or secondary to an 
increase in the production of EPO.
• Primary absolute (polycythemia vera)—
myeloproliferative disorder characterized by 
neoplastic proliferation of all marrow cell 
precursors independent of EPO.
• Secondary absolute—caused by physiologi-
cally appropriate release of EPO due to 
chronic hypoxemia, excessive production of 
EPO or an EPO-like substance in an animal 
with normal partial pressure of oxygen 
(PaO2), or by excessive exogenous administra-
tion of EPO or darbepoetin.
Cardiovascular, respiratory, nervous, renal/
urologic—blood hyperviscosity causes poor 
perfusion and oxygen delivery to tissues.
GENETICS
Mutations of the JAK2 gene have been 
associated with polycythemia vera in humans.
Relative erythrocytosis due to hemoconcen-
tration or splenic contraction is the most 
common cause of erythrocytosis.
• Reference intervals for PCV, hemoglobin, 
and RBC count vary with geographic location 
and breed.
• Animals living at high altitudes have higher 
PCV than those at sea level.
Species
• Excitable breeds and cats are prone to 
splenic contraction.• Greyhounds have higher PCV values 
(reference interval is 50–65%).
Primary absolute polycythemia vera—cats 
6–7 years; dogs 7 years or older.
Male cats, female dogs.
SIGNS
• Relative—excitement or dehydration.
• Absolute—lethargy, seizures, altered 
mentation, anorexia, epistaxis, mucous 
membrane hyperemia.
• Relative—dehydration and clinical evidence 
of fluid loss.
• Absolute—lethargy, low exercise tolerance, 
behavioral change, brick red or cyanotic 
mucous membranes, sneezing, epistaxis, large 
size and tortuosity of retinal and sublingual 
vessels, cardiopulmonary impairment.
• Primary absolute—variable degrees of 
splenomegaly, hepatomegaly, thrombosis, and 
hemorrhage; seizures.
• Secondary appropriate absolute—clinical 
signs of hypoxemia caused by chronic 
pulmonary disease, cardiac disease with 
right-to-left shunting, or hemoglobinopathy.
• Secondary absolute (inappropriate EPO 
secretion)—signs associated with neoplasia, 
space-occupying renal lesion, or endocrine 
disorder.
CAUSES
• Relative—hemoconcentration/dehydration 
or splenic contraction due to excitement.
• Primary absolute—rare myeloproliferative 
disorder.
• Secondary appropriate absolute—chronic 
pulmonary disease, cardiac disease or anomaly 
with right-to-left shunting, high altitude, 
methemoglobinemia, and impairment of 
renal blood supply.
• Secondary absolute caused by inappropriate 
EPO secretion (rare)—neoplasia (e.g., T-cell 
lymphoma, nasal fibrosarcoma, renal 
carcinoma, pheochromocytoma, cecal 
leiomyosarcoma), hyperadrenocorticism, 
hyperthyroidism, hyperandrogenism.
EPO or darbepoetin administration in 
animals undergoing therapy for anemia.
  DIAGNOSIS
• Moderately high PCV and total plasma 
protein with concurrent dehydration—sug-
gest relative polycythemia.
• Secondary absolute—caused by diseases 
that produce chronic hypoxemia or by 
space-occupying lesions of the kidney, endocrine disorders, neoplasms that produce 
EPO or an EPO-like substance independent 
of hypoxia, history of EPO administration.
• Polycythemia vera—diagnosed by 
elimination of other causes.
• Increased PCV or hematocrit.
• Physiologic leukocytosis (neutrophilia and 
lymphocytosis) may occur with splenic 
contraction.
• Serial monitoring of PCV—diagnosis of 
polycythemia vera requires an unexplained 
high PCV documented on multiple occasions 
(several weeks) with no underlying cause.
• Arterial blood gas analysis may demonstrate 
a low PaO2 in cases of secondary appropriate 
absolute erythrocytosis; pulse oximetry may 
also be used to assess oxygen saturation 
(SpO2).
• EPO measurement—not currently 
recommended due to lack of veterinary-
specific assays and extensive overlap in EPO 
concentration between normal and affected 
animals.
• Thyroid testing (cats).
IMAGING
Radiography and abdominal ultrasonography 
to detect cardiopulmonary disease and 
• Biopsy of any masses.
• Bone marrow aspirate.
Polycythemia vera—gross findings: general-
ized vascular congestion, arterial thrombosis, 
splenomegaly, diffusely red bone marrow with 
reduced fat; microscopic findings: hyperplas-
tic bone marrow with normal or reduced 
myeloid/erythroid ratio and reduced iron 
content.
  TREATMENT
• Relative—rehydration with IV fluids 
appropriate for primary cause; assessment of 
renal function, gastrointestinal system, 
acid-base status, and electrolyte balance; if 
not hemoconcentrated, allow patient to calm 
down.
• Absolute—phlebotomy recommended 
(20 mL/kg over 1 to several days) to reduce 
RBC mass to PCV of 55%; blood volume 
should be replaced concurrently with isotonic 
fluids.
• Secondary inappropriate absolute—  
phlebotomy combined with identification 
and removal of EPO source.
• Secondary appropriate absolute—  
phlebotomy and hydroxyurea. The high PCV

Canine and Feline, Seventh Edition  463
Eis an appropriate compensatory response; 
thus, phlebotomy may be dangerous; if 
indicated, remove blood at a lower volume 
(5 mL/kg). A higher PCV (60–65%) may be 
necessary to sustain life until the cause of 
hypoxemia can be corrected.
• Polycythemia vera—phlebotomy (20 mL/
kg) and hydroxyurea; frequency of bleeding 
and dosage adjusted to maintain a PCV of 
55% in dogs and 45% in cats.
Oxygen therapy may be indicated for patients 
with cyanosis, hypoxemia, cardiopulmonary 
disease, or weakness following phlebotomy.
ACTIVITY
Excessive exercise should be avoided.
DIET
Normal diet, free-choice water.
• Patients need to be observed at home for 
changes in activity, difficulty breathing, or 
bleeding.
• Patients treated with EPO for anemia must 
have PCV rechecked and dose adjusted at 
regular intervals.
If surgery is necessary, preoperative 
 phlebotomy and close monitoring of 
oxygenation and vital parameters may be 
necessary. Postoperatively, monitor for 
bleeding or thrombosis.
• Polycythemia vera—hydroxyurea (dogs: 
40–50 mg/kg PO divided twice daily; cats: 
30 mg/kg PO q24h).
• Erythrocytosis secondary to hypoxemia—
hydroxyurea (40–50 mg/kg PO q48h).
Phlebotomy may be contraindicated in 
hypoxemic patients.
• Rapid removal of blood can cause 
hypotension and cardiovascular collapse.
• Adverse effects of hydroxyurea include 
bone marrow hypoplasia with thrombocytopenia, anemia, and neutropenia, 
alopecia, changes in skin pigmentation, and 
sloughing of toenails.
• Methemoglobinemia and hemolytic 
anemia reported in cats treated with hydro  - 
xyurea.
Polycythemia vera—chlorambucil (dogs and 
cats: 0.2 mg/kg PO q24h) or busulfan 
(dogs: 2–4 mg/m2 PO q24h).
  FOLLOW-UP
• PCV, total protein, urine output, and 
bodyweight daily in severely dehydrated 
animals.
• Patients treated for polycythemia vera by 
chemotherapy—monitor weekly for changes 
in PCV, leukocytes, and platelets during 
initial treatment; then monthly for adjust-
ment of chemotherapy and periodic 
phlebotomy.
• Periodic assessment of bone marrow iron 
stores or serum iron levels is indicated to 
detect iron deficiency.
• Hyperviscosity in patients with absolute 
polycythemia, especially polycythemia vera, 
may lead to thrombosis, infarction, or 
• Chemotherapy may cause bone marrow 
suppression.
• Patients undergoing repeated phlebotomies 
can develop iron deficiency, hypoproteinemia, 
and peripheral edema.
• Relative erythrocytosis—fair to good 
prognosis depending on primary cause.
• Secondary absolute appropriate  
erythrocytosis—clinical course and prognosis 
are determined by the severity of the lesion 
causing hypoxemia.
• Secondary inappropriate absolute  
erythrocytosis—if the tissue source of 
excessive EPO secretion can be identified 
and removed or corrected, prognosis is good 
to fair depending on cause.• Primary absolute erythrocytosis (polycythemia 
vera)—prognosis is guarded, although cats 
have had survival times up to 5 years.
Hydroxyurea may arrest or inhibit 
spermatogenesis.
SYNONYMS
Polycythemia—although use of this term 
should be avoided, due to its similarity with 
polycythemia vera.
SEE ALSO
• Hyperviscosity Syndrome.
• Polycythemia Vera.
Cook SM, Lothrop CD. Serum erythropoietin 
concentrations measured by radioimmunoassay 
in normal, polycythemic, and anemic dogs 
and cats. J Vet Intern Med 1994, 8:18–25.
Darcy H, Simpson K, Gajanayake I, et al. 
Feline primary erythrocytosis: a multicenter 
case series of 18 cats. J Fel Med Surg 2018, 
1:1–7.
Randolph JF , Peterson ME, Stokol T. 2010. 
Erythrocytosis and polycythemia. In: 
Weiss DJ, Wardrop KJ, eds., Schalm’s 
Wiley-Blackwell, 2010, pp. 162–166.
available online(continued)  Erythrocytosis

464  Blackwell’s Five-Minute Veterinary Consult  
EEsophageal Diverticula
  BASICS
OVERVIEW
• Pouch-like sacculations of the esophageal 
wall that accumulate fluids and ingesta.
• Diverticula may be congenital or acquired 
and are rare.
• Pulsion diverticula occur secondary to 
increased intraluminal pressure. Seen with 
esophageal obstructive disorders such as 
foreign body or mass lesions.
• T raction diverticula occur secondary to 
periesophageal inflammation where fibrosis 
contracts and pulls out the wall of the 
esophagus into a pouch.
• Localized inflammation around (esophagitis) 
and lining the diverticulum may be present.
• Potential complications include ingesta 
impaction, mechanical obstruction (large 
diverticulum), and/or esophageal hypomotility.
• Organ systems affected include gastrointes-
tinal (regurgitation), musculoskeletal (weight 
loss), and respiratory (aspiration pneumonia).
• Rare; more common in dog than cat.
• Congenital or acquired (no genetic basis 
proven).
• No important breed or sex predisposition.
SIGNS
• Postprandial regurgitation, dysphagia, 
anorexia, coughing.
• Weight loss, respiratory distress.
Pulsion Diverticulum
• Embryonic developmental disorders of the 
esophageal wall.
• Esophageal foreign body, mass or focal 
motility disturbances (uncommon).
Traction Diverticulum
Inflammatory processes associated with the 
trachea, lungs, hilar lymph nodes, or 
pericardium; resultant fibrous connective 
tissue adheres to the esophageal wall.
  DIAGNOSIS
• Esophageal redundancy—barium contrast 
accumulation in the region of the thoracic inlet 
can occur normally in young dogs (especially 
brachycephalic breeds and Chinese Shar-Pei).
• Periesophageal mass—esophagram or 
esophagoscopy should differentiate the 
presence of a mass causing luminal 
narrowing.
• Esophageal foreign body.
• Hiatal hernia.
• Gastroesophageal intussusception.CBC/BIOCHEMISTRY/URINALYSIS
N/A
IMAGING
• Thoracic radiography—may show air or 
soft tissue opacity cranial to the diaphragm or 
cranial to the thoracic inlet.
• Contrast esophagram—shows contrast 
accumulation within the diverticulum.
• Videofluoroscopy—useful to evaluate for 
disturbances in esophageal motility.
Esophagoscopy confirms ingesta/debris 
within outpouchings of the esophagus.
  TREATMENT
• If the diverticulum is small and not causing 
significant clinical signs, treat conservatively with 
elevated feedings of a soft, bland diet followed by 
copious liquids or a semi-liquid diet.
• If the diverticulum is large or is associated 
with significant clinical signs, surgical 
resection is recommended.
• Client education should include the 
importance of dietary management and the 
potential for aspiration pneumonia.
• Fluid therapy, antibiotics, and aggressive 
nursing, if concurrent aspiration pneumonia 
is present; alternative enteral nutrition via 
gastrostomy tube may be necessary in patients 
• T reat for esophagitis if present.
• Drug therapy for esophagitis, if present.
• Proton pump inhibitors, such as omeprazole or 
pantoprazole, are potent and effective anti-secre -
tory agents (omeprazole: 0.7–1.5 mg/kg PO 
q12h; pantoprazole: 0.7–1.5 mg/kg IV once 
daily) for treatment of severe esophagitis.
• Use broad-spectrum antibiotics if patient 
has concurrent aspiration pneumonia; if 
recurrent or severe pneumonia is present, base 
antibiotic selection on culture and sensitivity 
of samples obtained by transtracheal wash or 
bronchoalveolar lavage.
N/A
  FOLLOW-UP
• Evaluate for evidence of infection or 
aspiration pneumonia.• Maintain positive nutritional balance 
throughout disease process.
Patients with diverticula and impaction are 
predisposed to perforation, fistula, stricture, 
and postoperative incisional dehiscence.
• Prognosis is guarded in patients with large 
diverticula and overt clinical signs. 
• Motility disturbances may persist 
post-surgery.
 INTERNET RESOURCES
https://www.vin.com/vin/default.aspx
Marks SL. Diseases of the pharynx and 
esophagus. In: Ettinger SJ, Feldman EC, 
Medicine, 8th ed. Philadelphia, PA: 
Sherding RG, Johnson SE. Esophagoscopy. 
In: Tams TR, Rawlings CA, eds., Small 
Animal Endoscopy, 3rd ed. Philadelphia, 
PA: Mosby, 2011, pp. 41–95.

Canine and Feline, Seventh Edition  465
EEsophageal Foreign Bodies
  BASICS
Ingestion of foreign material or foodstuffs 
too large to pass through the esophagus, 
causing partial or complete luminal 
Esophageal foreign bodies cause mechanical 
obstruction, mucosal inflammation with 
edema, and possibly ischemic necrosis and 
esophageal perforation.
• Respiratory—if aspiration pneumonia.
GENETICS
N/A
Unknown
N/A
Species
Due to the indiscriminate eating habits of 
many dogs, they have a higher incidence 
than cats.
More common in small-breed dogs; terrier 
breeds often overrepresented.
More common in young to middle-aged 
animals.
N/A
SIGNS
The pet may have been observed ingesting a 
foreign body.
Most common include retching, gagging, 
lethargy, anorexia, ptyalism, regurgitation, 
restlessness, dysphagia, odynophagia, and 
persistent gulping.
• Ptyalism.
• Can be unremarkable.
• Occasional discomfort when palpating the 
neck or cranial abdomen.
CAUSES
Occurs most often with an object whose size, 
shape, or texture does not allow free move  - 
ment through the esophagus, causing it to 
become lodged before it can pass.
• Indiscriminate eating habits.
• Access to foreign materials.  DIAGNOSIS
• Esophageal neoplasia.
• Other esophageal disorders.
• Occasionally, electrolyte abnormalities, an 
inflammatory leukogram, and/or hemocon-
centration, depending upon the severity of 
signs and degree of dehydration.
N/A
IMAGING
• Most esophageal foreign bodies are 
radiodense and are readily visualized. These 
objects most commonly lodge at points of 
minimal esophageal distension, including the 
thoracic inlet, base of the heart, and 
esophageal hiatus.
• Esophageal distension with air may be 
visualized cranial to the foreign body. 
Retained air in the esophagus is not always 
associated with esophageal foreign bodies.
• A contrast esophagram or videofluoroscopy 
is required to identify radiolucent objects. If 
perforation is suspected, use an aqueous 
organic iodide contrast agent for imaging 
studies.
• Air and/or fluid in the mediastinum or 
pleural space suggests esophageal perforation; 
depending on severity, this can be an 
indication for surgery versus esophagoscopy.
• Pulmonary infiltrates suggest aspiration 
Esophagoscopy allows removal of most (80%) 
foreign bodies using retrieval forceps. It also 
allows for visual inspection of the mucosa for 
trauma after foreign body removal. Use of an 
endoscope with an accessory channel 
diameter of >2.8 mm will allow use of the 
largest types of retrieval forceps.
N/A
  TREATMENT
• Emergencies—treat as inpatient and perform 
endoscopy as soon as possible after diagnosis.
• If endoscopic retrieval of the foreign body 
succeeds and esophageal damage is minimal, 
the patient may be discharged the same day.• Foreign bodies which cannot be removed 
through the mouth may be pushed aborally 
into the stomach.
• If the procedure to remove the foreign body 
is atraumatic and the esophagus has sustained 
minimal damage, no special aftercare is 
needed.
• Severe mucosal trauma may require placing 
a gastrostomy tube for enteral nutritional 
support during esophageal healing. Fluid 
therapy may also be required to maintain 
normal hydration status during periods of 
prolonged esophageal rest.
ACTIVITY
The patient may resume normal activity after 
a foreign body has been routinely removed.
DIET
• No change needed other than, perhaps, 
altering the food to a more liquid consistency.
• Feeding should be withheld 12–24 hours 
following foreign body removal.
Discuss the possibility of complications and 
repeat offenders.
• Surgery is indicated when endoscopy fails 
to retrieve the foreign body; when endoscopy 
enables advancement of the object into the 
gastric lumen but it is too large to pass 
through the gastrointestinal tract; or when a 
large esophageal perforation or area of 
necrosis requires resection.
• The short-term prognosis for esophageal 
surgery is dogs and cats is favorable (~90%).
• It is often less traumatic to advance a bone 
foreign body into the stomach than to attempt 
retrieval transorally via endoscopy. Gastrostomy, 
if required, may then be performed.
• Most bone foreign bodies can be safely 
left to dissolve in the stomach without need 
for surgical removal. Nondigestible foreign 
objects (wood, metal, plastic) passed into 
the stomach may need to be removed 
If there is significant mucosal injury (i.e., 
esophagitis), recommendations include:
• Sucralfate slurry (0.5–1 g/dog PO q8h) for 
mucosal cytoprotection and healing.
• Proton pump inhibitor (omeprazole or 
pantoprazole at 1 mg/kg q12h) for robust 
suppression of gastric acid secretions that may 
contribute to reflux esophagitis.
• Broad-spectrum antibiotics (amoxicillin or 
Clavamox®) are only administered to animals 
with mucosal perforation.

466  Blackwell’s Five-Minute Veterinary Consult  
E• Metoclopramide (0.2–0.5 mg/kg IV/SC/
PO q8h) or cisapride (0.5 mg/kg q8–12h 
PO) to stimulate gastric motility and 
minimize reflux esophagitis.
• Gastrostomy tube placement for enteral 
nutrition in animals with severe mucosal trauma.
N/A
N/A
N/A
N/A
 FOLLOW-UP
• Examine the esophagus closely via endo  - 
scopy for mucosal damage after foreign body 
removal.
• Mild erythema/erosions are not uncommon 
and tend to heal uneventfully.
• If an esophageal laceration/perforation is 
detected—gastrostomy tube feedings allow 
esophageal rest and healing.
• Advise post-procedural survey thoracic 
radiographs to assess for pneumomediastinum/
• Monitor at least 2–3 weeks for evidence of 
stricture formation.• Esophageal stricture—most common 
clinical sign is regurgitation with evidence of 
odynophagia in many animals; esophagram or 
videofluoroscopy and/or esophagoscopy may 
be indicated to confirm a stricture.
Carefully monitor the environment and what 
is fed to the pet.
• Approximately 25% of patients with 
foreign bodies develop complications.
• Complications most frequently encountered 
include esophageal perforation, esophageal 
strictures, esophageal fistulas, and severe 
esophagitis. Focal, transient esophageal 
motility disturbances can occur secondary to 
esophageal trauma.
• Pneumomediastinum, pneumothorax, 
pneumonia, pleuritis, mediastinitis, and 
bronchoesophageal fistulas can all occur 
secondary to perforation.
PROGNOSIS
• Most patients do well and recover 
• With complications, the prognosis is guarded.
None
None
N/A
SEE ALSO
• Esophageal Diverticula.
• Esophageal Stricture.
https://www.vin.com
Deroy C, Corcuff JB, Billen F , et al. Removal 
of oesophageal foreign bodies: comparison 
between oesophagoscopy and oesophagotomy 
in 39 dogs. J Small Anim Pract 2015, 
56:613–617.
Pratt CL, Reineke EL, Drobatz KJ. Sewing 
needle foreign body ingestion in dogs and 
cats: 65 cases (2000–2012). J Am Vet Med 
Assoc 2014, 245(3):302–308.
Sutton JS, Culp WTN, Scotti K, et al. 
Perioperative morbidity and outcome of 
esophageal surgery in dogs and cats: 72 
cases (1993-2013). J Am Vet Med Assoc 
2016, 249(7):787–793.
Tams TR. Endoscopic removal of gastrointesti -
nal foreign bodies. In: Tams TR, Rawlings 
CA, eds., Small Animal Endoscopy, 3rd ed. 
Philadelphia, PA: Mosby, 2011, pp. 247–295.
available onlineEsophageal Foreign Bodies  (continued)

Canine and Feline, Seventh Edition  467
EEsophageal Stricture
  BASICS
A fixed narrowing of the esophagus resulting 
in partial or complete obstruction.
• Benign strictures occur when there is 
circumferential erosion and ulceration of the 
esophageal mucosa; regardless of the initiating 
event, once esophagitis develops there is a 
decrease in the lower esophageal sphincter 
(LES) tone; this results in more acid reflux 
and subsequent worsening of esophagitis; 
once severe esophagitis is present, damage can 
extend to the lamina propria and muscularis 
layers of the esophagus; this incites fibroblas-
tic proliferation and contraction, leading to 
stricture formation. • Malignant strictures 
occur rarely in dogs and cats, and result from 
direct tumor invasion.
• Gastrointestinal—a single site of stricture is 
most common, although multiple strictures 
can occur anywhere through the esophagus.  
• Respiratory—regurgitation is common with 
strictures, increasing risk for aspiration 
GENETICS
N/A
Infrequent
Spirocerca lupi  granuloma occurs in the 
southern United States, parts of Europe, 
South Africa, and Israel.
Species
None
Any. Puppies and kittens with extraluminal 
compression of the esophagus from a vascular 
ring anomaly typically become symptomatic 
at weaning.
None
SIGNS
• Odynophagia, dysphagia, increased 
salivation, regurgitation, anorexia, and weight 
loss; signs tend to be progressive as the 
stricture progressively narrows. • If regurgita-
tion leads to aspiration pneumonia, cough 
and dyspnea can develop.
May have poor body condition secondary to 
malnutrition.CAUSES
• Reflux during anesthesia is the most 
common cause of benign esophageal stricture, 
accounting for about 65% of cases; decreased 
LES tone during anesthesia may promote 
gastroesophageal reflux, resulting in 
subsequent acid injury to the esophageal 
mucosa. • Esophageal foreign bodies (if >270° 
mucosal damage occurs). • Esophagitis from 
certain tablets and capsules; commonly 
incriminated drugs are doxycycline, 
clindamycin, alendronate, and aspirin. 
• Gastroesophageal reflux. • Prolonged 
vomiting of gastric contents. • Swallowing of 
caustic substances. • Esophageal neoplasia 
(squamous cell carcinoma and lymphoma 
most common). •  Spirocerca lupi  granuloma. 
• Iatrogenic trauma during endoscopy. 
• Vascular ring anomaly as an extraluminal 
cause for focal esophageal narrowing.
• General anesthesia, especially with drugs 
that decrease LES tone, when the patient is in 
T rendelenburg position, and in large-breed, 
deep-chested dogs positioned in sternal 
recumbency. • Oral medications given with a 
dry swallow. • Foreign body ingestion.
  DIAGNOSIS
• Megaesophagus. • Esophageal foreign body.  
• Esophageal neoplasia. • Extrinsic esophageal 
compression (mass, abscess). • Gastroesophageal 
reflux. • Vomiting (any cause). • Oropha -
ryngeal dysphagia. • Vascular ring anomaly.
IMAGING
• Thoracic radiographs—usually unremarkable 
unless aspiration pneumonia develops. 
• Videofluoroscopic barium swallow should 
identify most strictures; if videofluoroscopy is 
not available, barium swallow of liquid, paste, 
or food followed immediately by radiography 
is performed; peristalsis proximal to the 
stricture site can be abnormal with concurrent 
esophagitis; may demonstrate more than one 
stricture.
• Endoscopy—diagnostic test of choice.  
• A focal narrowing (single or multiple) is 
easily identified; there is an abrupt decrease in 
luminal diameter at the stricture site.  
• Usually the mucosa is normal (smooth and 
pink), but can appear hyperemic and 
ulcerated if esophagitis is present.PATHOLOGIC FINDINGS
• If an esophageal mass is present, biopsy with 
histopathology is warranted; otherwise, benign 
strictures are not typically biopsied. • Strictures 
can be focal, multifocal, or coalescing.
  TREATMENT
• Outpatient medical management is only 
successful for mild strictures; most strictures 
require intervention. • If there are complications 
(esophageal perforation, aspiration pneumonia), 
then inpatient care is required.
IV fluids may be necessary if the animal is 
dehydrated.
ACTIVITY
• Exercise restriction is not necessary after 
dilation. • If pneumonia is present, the degree 
of hypoxia will determine appropriate activity 
level.
DIET
• Recommend feeding a fat-restricted diet to 
enhance gastric emptying. • Canned food can 
be fed in small frequent amounts following 
dilation. • If a balloon esophagostomy (BE) 
tube is placed, supplemental nutrition can be 
provided as needed through the tube; for 
refractory cases, placement of a percutaneous 
endoscopic gastrostomy tube could be 
• Owners should be aware that dilation 
procedures are not always successful, and that 
multiple attempts are required in many 
patients; it is important that medical 
management for esophagitis be diligently 
employed following dilation procedures to 
reduce the risk of restricture. • Placement of a 
BE tube could be discussed if multiple 
dilation procedures are not feasible or desired, 
or in the case of severe stricture.
• First-line treatment of benign esophageal 
strictures is mechanical dilatation of the 
stricture; techniques have evolved from rigid 
bougienage, to flexible bougies, to balloon 
dilation; the theoretical advantage of balloon 
dilatation is that the forces applied to the 
stricture are a radial stretch, whereas some of 
the forces applied with bougienage are 
longitudinal, resulting in possibly greater 
potential for esophageal perforation. 
• Esophageal dilatation balloons are made of 
special plastic that makes the balloon 
extremely rigid when maximally inflated at 
high pressures; balloons are positioned within 
the stricture under direct endoscopic 
visualization; the balloon is slowly inflated 
with saline using a commercially available

468  Blackwell’s Five-Minute Veterinary Consult  
Einflation device until it reaches the manufac -
turer’s rated pressure for that balloon; to 
ensure adequate dilation of the stricture has 
occurred, inflation of the balloon with 
ioxhexol and fluoroscopic monitoring during 
inflation is recommended; inadequate stricture 
effacement is commonly seen if this procedure 
is only performed with endoscopy.  
• Initial balloon diameter is ideally selected 
following measured diameters of normal 
esophagus obtained via a contrast study 
during the procedure; if fluoroscopy is not 
available, a balloon diameter 50–100% larger 
than the estimated stricture diameter can be 
selected; it is important to avoid assuming size 
based on weight of the animal as this can 
result in under- or overestimation; the 
sequence of subsequent larger dilations is then 
determined by the degree of mucosal tearing, 
ideally visualized fluoroscopically; the final 
dilation diameter is usually chosen by the 
degree of mucosal tearing and the size of the 
normal esophagus for the patient. • BE tube 
placement is a newer treatment option; this 
device allows for balloon dilation twice daily 
for 4–6 weeks at home to prevent stricture 
recurrence; the small number of reported 
patients have had improved short- and 
long-term outcomes compared to other 
treatments; the BE tube is placed similarly to a 
standard esophagostomy tube after balloon 
dilation is performed; placement of the balloon 
is confirmed with fluoroscopy to ensure the 
balloon spans the length of the stricture and 
does not interfere with the upper or lower 
esophageal sphincter. • For persistent 
strictures, despite multiple balloon dilations, a 
salvage procedure with placement of a self-  
expanding or bioabsorbable stent can be 
employed; it is important that the stent be 
secured with sutures to prevent migration; 
esophageal stenting has been associated with 
adverse effects including ptyalism, regurgita -
tion, megaesophagus requiring removal, and 
incision infection/drainage; given the 
unpredictability for which patients will 
tolerate stent placement, this procedure 
should be considered only for highly 
refractory cases that fail BE tube placement. 
• Surgical management (resection and 
anastomosis) is typically only performed as a 
last resort.
• Following dilation, give sucralfate suspen-
sion (0.5–1 g/patient PO q6h) to reduce 
esophagitis and pain. • Medications for 
esophagitis are used, including cisapride (0.5–0.75 mg/kg PO q8h) to increase LES 
tone and enhance gastric emptying, and 
omeprazole (1 mg/kg PO q12h) to decrease 
gastric acidity.
Caustic substances and emetic medications.
• Esophageal perforation can occur with 
overzealous balloon dilation of the stricture, 
therefore incremental increase in balloon 
diameter is recommended. • Ineffective 
balloon dilation can occur with incomplete 
tearing of the stricture; monitoring with 
videofluoroscopy could be considered to 
monitor for this. • Using a balloon over a 
guidewire is the safest way to perform this 
procedure; perforation is most common when 
a guidewire is not used through the lumen of 
the balloon and the balloon tip is advanced 
accidentally into the esophageal wall—use 
caution.
Sucralfate may inhibit the absorption of other 
drugs.
• Metoclopramide can be used to increase 
LES tone. • Histamine H2-receptor blockers 
can be used to decrease gastric acid.
  FOLLOW-UP
Patients are monitored for signs of recurrent 
stricture, including regurgitation and 
gagging.
• Preanesthetic administration of cisapride 
decreases the number of reflux events in 
anesthetized dogs. • Preanesthetic administra-
tion of omeprazole will minimize the likeli  - 
hood of acid reflux. • Medications with 
ulcerogenic potential should be given with at 
least 6 mL of water or food.
• Complications of balloon dilatation 
include perforation, severe mucosal tearing 
and esophagitis, and stricture recurrence; 
with BE tube placement additional 
complications include infection at the tube 
site and migration of the tube beyond the 
stricture; this is typically well tolerated.  
• Complications with stent placement 
include hyperplastic tissue ingrowth or 
overgrowth, dysphagia, gagging, perceived 
discomfort, and stricture recurrence.  
• Aspiration pneumonia secondary to 
regurgitation.EXPECTED COURSE AND PROGNOSIS
• With standard balloon dilation, reported 
successful outcomes defined as ability to 
swallow at least semi-solid food range from 
71.4% to 88.0%, with 12–23.1% able to eat 
a normal diet. • With BE tube placement, the 
majority (66.7%; 8/12) of patients were able 
to eat a normal diet with no dysphagia. • The 
prognosis for esophageal neoplasia is poor, 
but these cases tolerate esophageal stents well.
None.
None.
N/A
SYNONYMS
• Esophageal narrowing. • Esophageal 
blockage or obstruction.
SEE ALSO
• Dysphagia.
• Esophageal Foreign Bodies.
• BE = balloon esophagostomy.
• LES = lower esophageal sphincter.
Lam N, Weisse C, Berent A, et al. Esophageal 
stenting for treatment of refractory benign 
esophageal strictures in dogs. J Vet Intern 
Med 2013, 27(5):1064–1070.
Leib MS, Dinnel H, Ward DL, et al. 
Endoscopic balloon dilation of benign 
esophageal strictures in dogs and cats. J Vet 
Intern Med 2001, 15:547–552.
Tan DK, Weisse CW, Berent AB, Lamb KE. 
Prospective evaluation of an indwelling 
esophageal balloon dilation feeding tube for 
treatment of benign esophageal strictures in 
cats and dogs. J Vet Intern Med 2018, 
32:693–700.
Authors  Melissa L. Milligan and Allyson 
Berent
Keith Richter
available onlineEsophageal Stricture  (continued)

Canine and Feline, Seventh Edition  469
EEsophagitis
  BASICS
Inflammation of the esophagus typically 
affecting the esophageal body and lower 
esophageal sphincter (LES).
• Disruption of esophageal defense mecha-
nisms can result in esophageal inflammation, 
most commonly due to the effects of gastric 
acid from gastroesophageal reflux (GER) or 
vomiting.
• Esophagitis can result in impaired 
esophageal motility and LES incompetence, 
which may result in further GER perpetuat-
ing esophageal damage.
• Gastrointestinal (GI)—esophagus and in 
the vomiting patient primary or secondary GI 
disease.
• Respiratory—regurgitation and GER may 
lead to aspiration pneumonia, reflux 
laryngitis, pharyngitis and/or rhinitis; 
respiratory signs may be covert presentation 
for GER.
Unknown—relatively common; probably 
underestimated, as most cases are not 
definitively diagnosed.
Worldwide, except when caused by Pythium  
spp. (US Gulf Coast) and Spirocerca lupi  
(southern states).
Species
Reflux esophagitis in brachycephalic breeds 
due to negative intrathoracic pressure upon 
inspiration increasing the tendency for GER 
and hiatal hernia (HH).
• Any age.
• Young animals with congenital esophageal 
HH and older animals that are anesthetized 
are at greater risk of developing reflux 
None
SIGNS
• Dysphagia (difficulty swallowing, gagging, 
retching).
• Odynophagia (pain when swallowing, 
repeated swallowing efforts, and extension of 
head and neck during swallowing).
• Hyporexia or anorexia.• Weight loss.
• Coughing and/or nasal discharge with 
aspiration pneumonia, reflux laryngitis, 
pharyngitis, and/or rhinitis.
• Oral and pharyngeal inflammation and/or 
ulceration with ingestion of caustic substances 
or oropharyngeal reflux of gastric acid.
• Fever and pain with ulcerative esophagitis 
or aspiration pneumonia.
• Halitosis, ptyalism, possibly pain on 
palpation of neck.
• Cachexia and weight loss, with chronicity.
• Nasal discharge and congestion with reflux 
rhinitis.
• Cough, increased bronchovesicular sound, 
pulmonary crackles, and dyspnea with 
aspiration pneumonia.
CAUSES
• Most commonly GER secondary to general 
anesthesia (Web Figure 1), hiatal hernia (Web 
Figure 2), persistent or chronic vomiting, and GI 
disease resulting in delayed gastric emptying.
• Gastroesophageal reflux disease (GERD) 
secondary to primary LES abnormality is 
poorly understood in veterinary patients.
• Esophageal retention of tablets or capsules 
(doxycycline, clindamycin, nonsteroidal 
anti-inflammatory drugs [NSAIDs], 
alendronate).
• Esophageal foreign body (Web Figure 3).
• Infectious agents— Pythium  spp., Spirocerca 
lupi, Candida  infection secondary to immune 
• Uncommonly esophageal tumors, radiation 
injury, megaesophagus, vascular ring 
anomalies, gastrinoma, eosinophilic esophagi-
tis and esophageal tubes.
• HH.
• GI or metabolic/endocrine disease resulting 
in vomiting or gastric hyperacidity.
• Preanesthetic fasting for prolonged periods 
(≥24h) increases risk for GER and gastric 
hyperacidity.
  DIAGNOSIS
• Esophageal foreign body—usually detected 
by survey radiography or esophagoscopy.
• Esophageal stricture—revealed by barium 
contrast radiography or esophagoscopy.
• Oropharyngeal dysphagia—diagnosed with 
videofluoroscopic swallow study.
• HH—may be diagnosed by thoracic 
radiographs or esophagoscopy; contrast 
esophagram with fluoroscopy may be 
required to document (Web Figure 2).• Megaesophagus—survey radiography 
revealing diffuse dilation of esophageal 
body.
• Esophageal diverticula—detected by survey 
or contrast radiography or esophagoscopy.
• Vascular ring anomaly—usually revealed by 
leftward deviation of trachea at heart base on 
survey thoracic radiographs, or barium 
contrast radiography as focal dilation of 
proximal esophageal body.
• Esophageal neoplasia—mass effect with 
possible esophageal dilation diagnosed with 
survey or contrast radiography, thoracic CT, 
or esophagoscopy.
Usually unremarkable; patients with 
ulcerative esophagitis or aspiration pneumo-
nia may have leukocytosis and neutrophilia.
IMAGING
• Survey thoracic radiography—often 
unremarkable, but may reveal mild esophageal 
dilation or fluid accumulation in distal 
esophagus; aspiration pneumonia may be 
evident; dilation of esophagus cranial to a 
stricture; esophageal foreign body, HH, or 
esophageal mass may be detected.
• Barium contrast esophagram (static images 
and/or fluoroscopic)—may reveal esophageal 
dilation with retention of barium, strictures, 
foreign bodies, or masses; fluoroscopic studies 
allow for evaluation of swallowing, esophageal 
motility, strictures that may not be apparent on a 
static esophagram, sliding HH (Web Figure 2), 
and GER (the latter two conditions may require 
abdominal compressions to demonstrate).
• Thoracic CT can be helpful for esophageal 
masses, foreign bodies, and HHs.
• Endoscopy and biopsy—most reliable 
means of diagnosis (Web Figures 1 and 3). 
Mild cases of esophagitis may appear normal. 
Visual findings of mucosal hyperemia and 
edema are common and in more severe cases 
ulceration. With GER, changes usually most 
apparent in distal third of esophagus. Gastro  - 
duodenoscopy may also be performed to 
evaluate for GI causes of vomiting that caused 
• Histopathology provides most definitive 
evidence of esophagitis, although endoscopy 
and biopsies usually reserved for cases 
unresponsive to therapy. Diagnostic quality 
esophageal biopsies difficult to obtain 
endoscopically due to tough stratified 
squamous epithelium.
• Endotracheal or transtracheal aspiration 
and/or bronchoalveolar lavage for cytology, 
and culture and sensitivity testing, may be 
considered in patients with aspiration 
Mucosal squamous hyperplasia or dysplasia 
with erosions and ulcers; lymphocytic 
plasmacytic and neutrophilic inflammation.

470  Blackwell’s Five-Minute Veterinary Consult  
E  TREATMENT
• Mildly affected animals can be managed as 
outpatients; those with more severe esophagi-
tis (persistent regurgitation, dehydration) and 
complications (aspiration pneumonia) require 
• Successful treatment of esophagitis involves 
addressing underlying risk factors and 
predisposing conditions when possible; gastric 
acid suppression to reduce esophageal mucosal 
injury; increasing LES pressure and promot-
ing gastric emptying to reduce GER; and 
protecting esophageal mucosa from further 
injury.
• Upright or elevated feeding will be of 
benefit with regurgitation associated with 
abnormal esophageal motility secondary to 
• Coupage and nebulization are provided for 
patients with aspiration pneumonia.
• IV fluids to maintain hydration in severe cases.
• Oxygen therapy may be necessary in 
DIET
• Fat-restricted diets recommended to 
minimize gastric acid production.
• With severe esophagitis oral food and water 
may need to be withheld until regurgitation 
resolved; gastrostomy tube feedings may be 
required.
• Advise upright or elevated feeding when 
there is esophageal dysmotility.
• Discuss potential complications, including 
aspiration pneumonia, esophageal stricture, 
esophageal perforation, and/or esophageal 
motility abnormalities.
• Percutaneous endoscopic gastrostomy or 
surgical gastrostomy tube placement in severe 
cases.
• Surgical correction for HH when medical 
management not effective.
• Esophageal surgery may be necessary for 
large perforations, difficult esophageal foreign 
bodies, or esophageal neoplasia, but should be 
avoided if possible.
Acid Suppression
• Most important therapy for treatment of 
GERD and associated esophagitis. H2-receptor 
antagonists (H2RAs) and proton pump 
inhibitors (PPIs) are two main classes of acid suppressors. PPIs provide superior gastric acid 
suppression compared to H2RAs.
• PPIs should be administered at dose of 
1 mg/kg PO or IV q12h. Most common PPIs 
prescribed are omeprazole and pantoprazole. 
Other choices include lansoprazole and 
esomeprazole.
• Fractionated enteric-coated omeprazole 
tablets remain effective despite disruption of 
the enteric coating. Tablets need to be cleanly 
split and cannot be crushed.
• In humans widespread media attention has 
concerned potential adverse effects of PPIs. 
Current evidence is inadequate to establish 
cause and effect for most associations. Caution 
should be exercised when prescribing PPIs as 
they are among the most overprescribed drugs 
in humans and veterinary medicine.
• Famotidine is most effective and commonly 
recommended H2RA given at dose of 
0.5–1.0 mg/kg PO/SC/IV q12h. Has 
diminished effect over time with repeated 
administration. Is appropriate for short-term 
gastric acid suppression, but long-term 
administration not advised.
• When prescribing a PPI, overlap with an 
H2RA during initial dosing is unnecessary.
• When discontinuing a PPI after >3–4 
weeks of therapy, PPI should be gradually 
tapered by 50% increments over 2–3 weeks to 
avoid rebound gastric hyperacidity.
• Dosing for metabolic disease (renal failure 
and liver failure) not established; lower dose 
or longer dose interval may be appropriate for 
these conditions.
GI Prokinetics
• Second most common class of drugs used 
to treat GER and esophagitis. Increase LES 
pressure and promote gastric emptying, 
therefore reducing GER.
• Most effective is cisapride at 0.5–1.0 mg/kg 
PO q8h. Readily available from compounding 
pharmacies.
• Metoclopramide is GI prokinetic with 
antiemetic effects in dogs dosed at 0.2–
1.0 mg/kg PO/SC q8h or 1.0–3.0 mg/kg/
day as CRI.
Mucosal Protectants
• Sucralfate 0.25–1.0 g PO q6–8h is given as 
suspension mixed into slurry with water and 
administered on empty stomach. Forms 
insoluble complex that binds to inflamed 
tissue, creating protective barrier and 
preventing further damage caused by pepsin, 
acid, and bile. Additionally increases mucosal 
defense and repair mechanisms through 
stimulation of bicarbonate and prostaglandin 
E production and binding of epidermal 
growth factor, at neutral pH. Reported to 
relieve symptoms in humans.
• Antibiotics indicated with aspiration 
pneumonia, severe esophageal ulceration, and 
• Analgesics, especially in severe cases—  lidocaine solution (2.0 mg/kg PO q4–6h) for 
local analgesia; tramadol 2–4 mg/kg PO 
q8–12h.
• Anti-inflammatory dosage of corticosteroids 
(e.g., prednisone 0.5–1 mg/kg PO per day or 
divided q12h) may decrease fibrosis and 
esophageal stricture formation in severe cases; 
controversial and efficacy not been supported 
by literature. Avoid when evidence of aspiration 
None
None
Sucralfate may interfere with GI absorption 
of other drugs and it is best to separate dosing 
by 2 hours from other drugs; may not be 
clinically important.
• Narcotic analgesics including buprenor-
phine, methadone, and fentanyl may be 
necessary in severe cases of painful esophagitis.
• Ranitidine 2.0 mg/kg PO q12h, nizatidine 
2.5–5.0 mg/kg PO q24h, and erythromycin 
0.5–1.0 mg/kg PO/IV have GI prokinetic 
effects and may be alternate or additive 
drugs.
  FOLLOW-UP
• For patients with mild esophagitis, 
monitoring of clinical signs is sufficient.
• Consider follow-up endoscopy in patients 
with ulcerative esophagitis and those at risk 
for esophageal stricture.
• Consider two doses of omeprazole 1 mg/kg 
PO or famotidine 1 mg/kg PO given 12–24h 
and 1–4h prior to anesthesia to reduce gastric 
acidity.
• Prokinetic drug (cisapride 1 mg/kg PO; 
metoclopramide 0.2–1.0 mg/kg PO/SC) with 
acid suppressor may also help reduce GER 
during anesthesia and surgery.
• Maropitant useful to prevent vomiting and 
regurgitation associated with opioid premedi  - 
cations and anesthesia.
• If GER is cause of esophagitis, owners 
should avoid late-night feedings that tend to 
diminish LES pressure during sleep.
• Proper patient preanesthesia fasting decreases 
risk of GER. Withholding water for 4–8h 
and food for 8–12h prior to anesthesia is 
• Follow oral administration of capsules and 
tablets with 5–10 mL bolus of water 
(especially for doxycycline) amd a meal, or 
give with a treat such as a pill pocket to hasten Esophagitis  (continued)

Canine and Feline, Seventh Edition  471
Etransit time of pills to stomach. Coating pills 
with butter or applying Nutri-Cal® to the nose 
to stimulate licking after administration of 
tablets may also be effective.
• Esophageal stricture formation.
• Chronic reflux esophagitis.
• Permanent esophageal dysmotility.
• Chronic cough due to laryngopharyngeal 
aspiration or tracheal microaspiration.
• Esophageal perforation (rare).
• Barrett’s esophagus (rare complication of 
chronic reflux esophagitis reported in cats).
• Best results when treated with gastric acid 
suppressant, GI prokinetic, and possibly 
mucosal protectant.
• Mild esophagitis—good to excellent 
• Severe or ulcerative esophagitis—greater 
potential for complications, which warrants 
guarded prognosis.
• Complete recovery can be expected 
especially when treated before serious 
complications develop.  MISCELLANEOUS
None
H2RAs, PPIs, and glucocorticoids should all 
be used with caution during pregnancy.
SYNONYMS
Esophageal inflammation.
SEE ALSO
• Hiatal Hernia.
• GER = gastroesophageal reflux.
• GERD = gastroesophageal reflux disease.
• H2RA = H2 receptor antagonist.
• HH = hiatal hernia.
• LES = lower esophageal sphincter.• NSAID = nonsteroidal anti-inflammatory 
drug.
• PPI = proton pump inhibitor.
Garcia RS, Belafsky PC, DellaMaggiore A, 
et al. Prevalence of gastroesophageal reflux 
in cats during anesthesia and effect of 
omeprazole on gastric pH. J Vet Intern Med 
2017, 31(3):734–742.
Golly E, Odunayo A, Daves M, et al. The 
frequency of oral famotidine administration 
influences its effect on gastric pH in cats over 
time. J Vet Intern Med 2019, 33(2);544–550.
protectants in dogs and cats. J Vet Intern 
Tolbert K, Odunayo A, Howell RS, et al. 
Efficacy of intravenous administration of 
combined acid suppressants in healthy dogs. 
J Vet Intern Med 2015, 29:556–560.
Author  Steve Hill
available online(continued)  Esophagitis

472  Blackwell’s Five-Minute Veterinary Consult  
EEssential Oils Toxicosis
  BASICS
OVERVIEW
• Essential oils—volatile, organic constituents 
extracted from plants; contribute to  fragrance/  
taste. Often used as natural remedies by 
owners for their own medical issues. Essential 
oil insecticides (low %) manufactured for use 
on animals.
• Known toxicants to cats—d-Limonene 
(citrus oil), pine oil, ylang ylang oil, pepper  - 
mint oil, cinnamon oil.
• Known toxicants to cats and dogs —winter-
green oil, sweet birch oil, eucalyptus oil, clove 
oil, tea tree (aka melaleuca) oil.
• Known toxicants to dogs—pennyroyal oil.
• Cardiovascular—bradycardia, peripheral 
vasodilation.
• Endocrine/metabolic—hypothermia.
• Gastrointestinal (GI)—hypersalivation, 
vomiting.
• Hepatobiliary—elevated liver enzymes 
(LEs), hepatic failure.
• Nervous—ataxia, tremors, CNS depression.
• Respiratory—respiratory irritation/distress.
• Skin—irritation, possible ulceration.
Cats are more sensitive than dogs. Cats lack 
glucuronyl transferase; cannot metabolize/
eliminate toxins via hepatic glucuronidation.
SIGNS
• Signs vary based on type/concentration of 
oil. Higher the concentration the greater the 
risk. Only 7–8 drops of 100% oil may be 
needed to cause toxicosis.
• Onset—1–8 hours post exposure.
• Animal may smell of oil (hair coat, skin, 
breath) or feel greasy.
• Nausea, hypersalivation, vomiting, 
abdominal pain.
• Ataxia, tremors, CNS depression.
• Coughing, wheezing, panting, tachypnea, 
• Bradycardia, hypotension.
• Elevated LEs (cats, sometimes dogs—pen-
nyroyal oil).
• Passive oil diffusers—animals inhale odor, 
develop mild to severe respiratory irritation/
distress.
• Active diffusers—release micro-droplets of 
oil. Respiratory difficulties, but droplets can 
land on animal’s coat causing direct absorp-
tion or ingestion via grooming.
• History of preexisting respiratory issues 
(e.g., asthmatic cats) places animals at greater 
risk.• Indirect ingestion—essential oils used on 
human skin, animal licks skin.
• Direct dermal or oral use as owners try natural 
remedies (e.g., flea control) on their animals.
  DIAGNOSIS
• Aspirin toxicity—wintergreen and sweet 
birch oil contain methyl salicylate; anemia/GI 
hemorrhage may develop.
• Hepatotoxins xylitol, acetaminophen, 
cycads (sago palm), others.
• Toxins or conditions that affect CNS—  
ethylene glycol, hypoglycemia, hypotension, 
drug overdoses.
• Most often no specific diagnostic features.
• CBC and chemistry—possible increase in LEs.
IMAGING
• Thoracic radiographs with respiratory 
irritation/distress.
• Abdominal radiographs if abdominal pain.
Limited data—lesions of severe hepatic 
necrosis with pennyroyal oil.
  TREATMENT
Fresh air, emergency examination, bathing, 
inpatient care until signs resolve.
• Intravenous crystalloids.
• Prevent aspiration of vomitus.
• Oxygen therapy.
• Monitor BP , heart rate, thermoregulation.
Diet
Do not feed patients that are vomiting, 
having CNS signs, or are in respiratory 
distress.
• No specific antidote.
• Bathe with warm water and liquid hand 
dishwashing detergent.
• Activated charcoal (AC) with a cathartic × 1 
in large or concentrated oral ingestions. 
Repeat AC only q8h × 2 doses if tea tree oil 
(enterohepatic recirculation).
• Fluid boluses or vasopressors as needed for 
hypotension.• Anticholinergics if bradycardic, as long as 
normotensive.
• Bronchodilators with respiratory distress.
• Anti-emetics.
• Hepatoprotectants with elevated LEs.
Do not induce vomiting. Do not give AC to 
a patient with CNS signs.
Use hepatically metabolized medications with 
caution in the presence of LE elevation.
  FOLLOW-UP
Recheck LEs 48–72 hours post discharge, 
then as needed based on values and clinical 
signs.
• Do not apply essential oils directly to 
animals.
• Use essential oil products manufactured for 
use on animals with caution.
• Avoid using essential oil diffusers.
• Aspiration pneumonia—if neurologic 
patient with concurrent GI signs.
• Pennyroyal oil—disseminated intravascular 
coagulation, chronic hepatic insufficiency.
• Prognosis—good if treated early and 
aggressively. May take several days for 
complete resolution.
• More guarded prognosis with use of 100% 
oil (i.e., tea tree oil, pennyroyal oil), especially 
if treatment is delayed or inadequate. 
Fatalities can occur.
• AC = activated charcoal.
• LEs = liver enzymes.
Hovda L, Brutlag A, Poppenga R, et al. 
Essential oils/liquid potpourri; Tea tree oil/
melaleuca oil. In: Hovda LR, Brutlag AG, 
Poppenga RH, Peterson KL, eds., Five-
Minute Veterinary Consult Clinical 
Companion: Small Animal Toxicology, 2nd 
ed. Ames, IA: Wiley-Blackwell, 2016, pp. 
585–591, 592–597.
Author  Kia J. Benson

Canine and Feline, Seventh Edition  473
EEthanol Toxicosis
  BASICS
OVERVIEW
• Ethanol (CH3CH2OH)—short-chain 
alcohol; highly miscible with water; less 
volatile than comparable hydrocarbons (e.g., 
ethane); solvent for medications; component 
of alcoholic beverages; metabolized to 
acetaldehyde.
• Used intravenously to treat ethylene glycol 
poisoning.
• Denatured forms may contain other toxic 
fractions (e.g., acetone, benzene, camphor, 
castor oil, phthalates, kerosene, sulfuric acid, 
terpinols); may complicate effects.
• Ethanol concentration—expressed as proof 
(twice the % concentration).
• Acute oral lowest toxic dosage—5–8 mL/kg 
as pure alcohol; consider % alcohol in specific 
product consumed.
• Other alcohols—toxicity of methanol is 
similar to that of ethanol; the LD50 of 70% 
isopropanol is 2 mL/kg.
• Cell membrane damage; impaired sodium 
and potassium nerve conduction.
• May inhibit glutamate receptors in brain 
with reduction of cyclic guanosine monophos  - 
phate (GMP).
• Most common in dogs.
• No breed or sex predilections.
• Young, curious animals more susceptible.
SIGNS
• CNS—develop within 15–30 minutes after 
ingestion on an empty stomach or 1–2 hours 
on a full stomach; ataxia, reduced reflexes, 
behavioral changes, excitement, depression.
• Cardiovascular—cardiac arrest.
• Gastrointestinal—flatulence (bread dough).
• Respiratory—respiratory depression, 
narcosis.
• Urologic—polyuria, incontinence.
• Alcoholic beverages, either accidental or 
intentional, are most common source.
• Exposure to deicers, sanitizers, mouthwash, 
dyes, inks, some fuels, paint, varnishes, 
perfume, pharmaceuticals.
• Exposure to rising bread doughs containing 
active yeast.
• Fermented products—rotten apples, 
garbage.
• Dermal exposure—alcohol-containing 
products.  DIAGNOSIS
• Other alcohols—methanol, isopropanol, 
butanol.
• Human drugs of abuse—marijuana, 
barbiturates, benzodiazepines.
• Early stages of ethylene glycol (antifreeze) 
• Early stages of xylitol toxicosis.
• Halogenated or aliphatic hydrocarbon 
solvents.
• Hypoglycemia inducing metabolic and 
neurologic disorders.
• Pesticides—amitraz, macrolide 
antiparasiticides.
• PCV and total solids.
• Monitor for hypoglycemia; blood glucose 
<60 mg/dL considered serious.
• Metabolic acidosis likely from ethanol-induced 
lactic acidemia.
• Blood ethanol levels routinely available at 
reference labs—clinical signs in puppies at 
>0.6 mg/mL and in adults at >1–4 mg/mL.
• Blood methanol and isopropanol levels 
available at some reference labs.
• Blood gases and increased anion gap—  
evaluate potential acidosis.
N/A
  TREATMENT
• Activated charcoal—not effective.
• Emesis or gastric lavage—only in very 
recent exposures (less than 15 minutes) due 
to rapid absorption and rapid onset of clinical 
signs.
• Respiratory depression—provide artificial 
• IV isotonic crystalloid fluids—correct 
dehydration.
• Acidosis—sodium bicarbonate if pH <7.0, 
BE <15 mmHg, HCO3 <11 mmHg.
• Cardiac arrest—cardiac therapy (see 
Cardiopulmonary Arrest).
• Hemodialysis—may aid in elimination of 
ethanol after life-threatening exposure.
• Yohimbine may be effective for CNS 
depression.  MEDICATIONS
• Dextrose—0.5–1.5 ml/kg 50% dextrose 
diluted 1 : 4 in 0.9% NaCl as a bolus for 
immediate correction of severe hypoglycemia; 
2.5–5% dextrose supplementation in fluids 
for hypoglycemia.
• Fomepizole (4-methylpyrazole)—not 
specifically cleared for use in ethanol 
intoxication
• Sodium bicarbonate (if needed)—mEq of 
bicarbonate required = 0.5 × bodyweight in 
kg × (desired total CO2 mEq/L − measured 
CO2 mEq/L); give half the total calculated 
dose slowly over 3–4 hours IV; recheck 
blood gases and clinical status of the 
animal.
Avoid other CNS depressants.
  FOLLOW-UP
• Monitor for metabolic acidosis—blood pH, 
blood gases, urine pH, anion gap.
• Recovery from clinical signs—usually 
within 8–12 hours.
• GMP = guanosine monophosphate.
Dorman DC. Alcohols (ethanol, methanol, 
isopropanol). In: Hovda LR, Brutlag AG, 
Poppenga RH, Peterson KL, eds., Blackwell’s 
Five-Minute Veterinary Consult: Small 
Animal Toxicology, 2nd ed. Ames, IA: 
Wiley-Blackwell, 2016, pp. 71–77.
Kammerer M, Sachot E, Blanchot D. Ethanol 
toxicosis from ingestion of rotten apples by 
a dog. Vet Hum Toxicol 2001, 
43(6):349–350.
Means C. Bread dough toxicosis in dogs. J 
Vet Emerg Crit Care 2003, 13(1):39–41.
Gary D. Osweiler

474  Blackwell’s Five-Minute Veterinary Consult  
EEthylene Glycol Toxicosis
  BASICS
Results primarily from ingesting substances 
containing ethylene glycol (EG; e.g., 
antifreeze). Rarely from other products.
• EG—rapidly absorbed from the gastrointestinal 
tract; food in the stomach delays absorption.  
• Toxicity—initially causes CNS depression, 
ataxia, gastrointestinal irritation, and polyuria or 
polydipsia; rapidly metabolized in the liver by 
alcohol dehydrogenase to glycoaldehyde, 
glycolic acid, glyoxalic acid, and oxalic acid; 
leads to severe metabolic acidosis and renal 
epithelial damage. • Minimum lethal dosage—
cats: 1.4 mL/kg; dogs: 6.6 mL/kg.
• Gastrointestinal—irritated mucosa.  
• Nervous—inebriation from EG and 
glycoaldehyde owing to inhibition of 
respiration, glucose metabolism, and serotonin 
metabolism, and alteration of amine concen -
trations. • Renal/urologic—  initially, osmotic 
diuresis; later, metabolites, especially calcium 
oxalate monohydrate crystals, are directly 
cytotoxic to renal tubular epithelium, resulting 
in renal failure; mechanism of toxicity is now 
thought to involve attachment of oxalate to 
cell plasma membrane, activation of enzyme 
activity, and production of free radicals and 
lipid peroxidation, leading to cell necrosis.
• Common in small animals. • Highest 
fatality rate of all poisons; fatality rates higher 
for cats than dogs. • Incidence similar in cats 
and dogs.
Higher incidence in colder areas where 
antifreeze is more commonly used.
Species
Dogs, cats, and many other species, including 
birds.
• Any age susceptible (3 months–13 years).
• Mean: 3 years.
SIGNS
• Dose dependent. • Almost always acute.  
• Caused by unmetabolized EG and its toxic 
metabolites (frequently fatal).
• Early—from 30 minutes to 12 hours post 
ingestion in dogs: nausea and vomiting; mild 
to severe depression; ataxia and knuckling; 
muscle fasciculations; nystagmus; head 
tremors; decreased withdrawal reflexes and 
righting ability; polyuria and polydipsia. • Dogs—with increasing depression, patient 
drinks less but polyuria continues, resulting 
in dehydration; CNS signs abate transiently 
after approximately 12 hours, but recur later. 
• Cats—usually remain markedly depressed; 
do not exhibit polydipsia. • Oliguria (dogs: 
36–72 hours; cats: 12–24 hours) and anuria 
(72–96 hours post ingestion)—often develop 
if untreated. • May note severe hypothermia. 
• Severe lethargy or coma. • Seizures. 
• Anorexia. • Vomiting. • Oral ulcers. 
• Salivation. • Kidneys—often swollen and 
painful, particularly in cats.
CAUSES
Ingestion of EG, the principal component 
(95%) of most antifreeze solutions.
Access to EG—widespread availability; 
somewhat pleasant taste; small minimum 
lethal dose; lack of public awareness of toxicity.
  DIAGNOSIS
• Acute (30 minutes–12 hours post 
 ingestion)—ethanol, methanol, and 
marijuana toxicosis; ketoacidotic diabetes 
mellitus; pancreatitis; gastroenteritis. • Renal 
stage—acute renal failure by nephrotoxins, 
e.g., aminoglycoside antibiotics, amphotericin 
B, cancer chemotherapeutic drugs, ibuprofen, 
oxalate-containing plants such as philodendrons, 
plants of the lily family (cats), cyclosporin, 
grape and raisin toxicosis (causes hypercalcemia, 
unlike EG toxicosis), and heavy metals; 
leptospirosis, tubulointerstitial nephritis; 
glomerular and vascular disease; renal 
ischemia (hypoperfusion).
• Packed cell volume (PCV) and total 
protein—often high owing to dehydration. 
• Stress leukogram— common. • High blood 
urea nitrogen (BUN) and creatinine—dog: 
36–48 hours post ingestion; cat: 12 hours 
post ingestion. • Hyperphosphatemia may 
occur transiently 3–6 hours post ingestion, 
owing to phosphate rust inhibitors in 
antifreeze; hyperphosphatemia is also seen 
with azotemia owing to decreased glomerular 
filtration. • Hyperkalemia if oliguric or anuric. 
• Hypocalcemia—occurs in approximately 
half of patients, owing to chelation of calcium 
by oxalic acid; clinical signs infrequently 
observed because of acidosis. 
• Hyperglycemia—occurs in approximately 
half of patients, owing to inhibition of 
glucose metabolism by aldehydes, increased 
epinephrine and endogenous corticosteroids, 
and uremia. • Isosthenuria—by 3 hours post 
ingestion, owing to osmotic diuresis and 
serum hyperosmolality-induced polydipsia; 
continues in later stages of toxicosis because of renal dysfunction. • Calcium oxalate 
crystalluria—consistent finding; as early as 3 
hours post ingestion in cats and 6 hours in 
dogs; monohydrate form more common. 
• Urine—pH consistently decreases; 
inconsistent findings—hematuria; proteinuria; 
glucosuria; may note granular and cellular 
casts, white blood cells (WBCs), red blood 
cells (RBCs), and renal epithelial cells.
Blood Gases
• Metabolites cause severe metabolic 
acidosis. • Total CO2, plasma bicarbonate 
concentration, and blood pH—low by 3 
hours post ingestion; markedly low by 12 
hours. • Partial pressure of CO2 (PCO2) 
decreases, owing to partial respiratory 
compensation. • Anion gap—increased by 
3 hours post ingestion; peaks at 6 hours 
post ingestion; remains increased for 
approximately 48 hours (EG metabolites 
are unmeasured anions. Glycolate, a 
metabolite of EG, can result in a false 
increase in plasma lactate, which could lead 
to the assumption that acidosis is due to 
increased lactate, rather than EG toxicosis.
Other
• Serum osmolality and osmole gap—high by 
1 hour post ingestion, in parallel with serum 
EG concentrations; dose related; usually 
remain high for approximately 18 hours post 
ingestion; EG toxicosis most common 
cause of high osmolal gap. • EG serum 
concentration— peaks 1–6 hours post 
ingestion; usually not detectable in serum or 
urine by 72 hours. • Commercial kits—PRN 
Pharmacal REACT EG measures concentra-
tions at >50 mg/dL; estimate by multiplying 
osmole gap by 6.2. ◦ Test does not detect 
metabolites, so must be used within the first 
few hours post ingestion. ◦ Results available 
in 6 minutes but should not be read over 10 
minutes. ◦ Labeled for dogs and cats; some 
cats may have toxicosis at levels below 50 mg/
dL. ◦ False-positive test results can be seen 
with propylene glycol, glycerol, mannitol, and 
sorbitol. Ethanol may combine with 
propylene glycol or glycerol to give a false 
positive. • Wood’s lamp examination of 
urine, face, paws, or vomitus may detect 
fluorescein that is sometimes added to 
antifreeze to detect radiator leaks. This 
method is nonspecific and may be unreliable; 
fluorescein has a half-life of approximately  
4 hours.
IMAGING
Ultrasonography—renal cortices may be 
hyperechoic as a result of crystals.
• Kidney biopsy—with anuria; confirm 
diagnosis. • Cytologic examination of kidney 
imprints—often diagnostic; numerous 
calcium oxalate crystals.

Canine and Feline, Seventh Edition  475
EPATHOLOGIC FINDINGS
• Kidneys often swollen.
• Postmortem examination of kidney reveals 
the presence of calcium oxalate crystals in the 
tubules.
  TREATMENT
• Cats—usually inpatient.
• Dogs—usually outpatient if <5 hours post 
ingestion and treated with fomepizole; 
inpatient if >5 hours for IV fluids to correct 
dehydration, increase tissue perfusion, and 
promote diuresis.
• Goals—prevent absorption; increase 
excretion; prevent metabolism. • Induction 
of vomiting and gastric lavage with activated 
charcoal not recommended unless can be 
performed in first 30 minutes following 
ingestion due to rapid absorption of EG. • IV 
fluids—correct dehydration, increase tissue 
perfusion, and promote diuresis; accompa-
nied by bicarbonate given slowly IV to correct 
metabolic acidosis. • Monitor serial plasma 
bicarbonate concentrations—0.5 × body 
weight (kg) × (24 – plasma bicarbonate) = 
sodium bicarbonate needed (mEq). 
• Monitor urine pH in response to therapy. 
• Azotemia and oliguric renal failure 
(dogs)—most of the EG has been metabo-
lized; little benefit from inhibition of alcohol 
dehydrogenase (ADH); correct fluid, electrolyte, 
and acid-base disorders; establish diuresis; 
diuretics (particularly mannitol) may help; 
hemodialysis or peritoneal dialysis may be 
useful; may need extended treatment (several 
weeks) before renal function reestablished.
Kidney transplantation—successfully employed 
in cats with EG-induced renal failure.
Dogs
Fomepizole (4-methyl pyrazole, available 
from Kacey Diagnostics)—effective and 
nontoxic liver ADH inhibitor; much more 
expensive than ethanol but less intensive care 
required; 5% (50 mg/mL) at 20 mg/kg IV 
initially; then 15 mg/kg IV at 12 and 24 
hours; then 5 mg/kg IV at 36 hours.Cats
• Fomepizole—cats must be given a higher dose 
of fomepizole than dogs; 125 mg/kg IV initially, 
then 31.25 mg/kg at 12, 24, and 36 hours. 
• Ethanol—use if fomepizole not available; 
20% at 5mL/kg diluted in fluids and given in 
an IV drip over 6 hours for 5 treatments; then 
over 8 hours for 4 more treatments.
Avoid drugs that cause CNS depression, 
including ethanol.
• Competitive substrates (alcohols, such as 
ethanol) contribute to CNS depression; 
monitor respiration. • Cats may become 
hypothermic; require heat. • Other pyra-
zoles—may be toxic to the marrow and liver; 
do not substitute for fomepizole.
• Fomepizole—contributes slightly to CNS 
depression in cats; none in dogs. • Ethanol—
contributes to CNS depression; further 
increases serum osmolality.
• Ethanol, propylene glycol, and 
1,3-butanediol—have higher affinity for 
ADH than does EG; effectively inhibit EG 
metabolism; may cause CNS depression 
and increase serum osmolality; constant 
serum ethanol concentrations of 100 mg/
dL will inhibit most EG metabolism. 
• Ethanol treatment requires hospitaliza -
tion, constant IV infusion (ethanol and 
fluids); continuous monitoring for 
respiratory and acid-base status.
  FOLLOW-UP
BUN, creatinine, acid-base status, and urine 
output—monitored daily.
• Increasing client awareness of toxicity—
helps prevent exposure; earlier treatment of 
patients. • Use of antifreeze products (e.g., 
Sierra®, Prestone LowTox®) that contain 
propylene glycol, which is much less toxic.
• Without azotemia—usually no complica-
tions. • Urine concentrating ability—may be 
impaired with azotemia; may recover.
• Untreated—oliguric renal failure (dogs: 
36–72 hours; cats: 12–24 hours); anuria by 
72–96 hours post ingestion. • Dogs treated <5 hours post ingestion—prognosis excellent 
with fomepizole treatment. • Dogs treated up 
to 8 hours post ingestion—most recover. 
• Dogs treated up to 36 hours post ingestion— 
may be of benefit to prevent metabolism of any 
remaining EG. • Cats treated within 3 hours 
post ingestion—prognosis good. • If a large 
quantity of EG is ingested, prognosis is poor, 
unless treated within 4 hours of ingestion. 
• Patients with azotemia and oliguric renal 
failure—prognosis poor; almost all of the EG 
will have been metabolized.
Patients <6 months of age with oliguric renal 
failure sometimes fully recover.
SYNONYMS
Antifreeze poisoning.
SEE ALSO
Hyperosmolarity
• ADH = alcohol dehydrogenase. • BUN = 
blood urea nitrogen. • EG = ethylene glycol. 
• PCO2 = partial pressure of carbon dioxide. 
• PCV = packed cell volume. • RBC = red 
blood cell. • WBC = white blood cell.
Connally HE, Thrall MA, Forney SD, et al. 
Safety and efficacy of 4-methylpyrazole as 
treatment for suspected or confirmed 
ethylene glycol intoxication in dogs: 107 
cases (1983–1995). J Am Vet Med Assoc 
1996, 209:1880–1883.
Connally HE, Thrall MA, Hamar DW. Safety 
and efficacy of high-dose fomepizole 
compared with ethanol as therapy for 
ethylene glycol intoxication in cats. J Vet 
Emerg Crit Care 2010, 20(2):191–206.
Tart KM, Powell LL. 4-Methylpyrazole as a 
treatment in naturally occurring ethylene 
glycol intoxication in cats. J Vet Emerg Crit 
Care 2011, 21(3):268–272.
Authors  Mary Anna Thrall, Gregory F . Grauer, 
Heather E. Connally, and Sharon M. Dial
available online(continued)  Ethylene Glycol Toxicosis

476  Blackwell’s Five-Minute Veterinary Consult  
EExcessive Vocalization and Waking at Night—Dogs and Cats
  BASICS
• Vocalization that is uncontrollable, 
excessive, at inappropriate times of day or 
night, or that disrupts owners, neighbors, or 
other animals.
• In night-time waking, the pet wakes during 
the night, does not fall asleep at bedtime, or 
awakens early, leading to disruption of 
owner’s sleep.
• Varies with cause.
• Barking may be normal canine communication 
(social, threat, warning, care-soliciting) but 
unacceptable to owners.
• Owner responses may reinforce or increase 
anxiety (punishment).
• Cats are crepuscular, so early morning 
waking may be normal.
• May be due to medical conditions that 
cause anxiety, discomfort, irritability, or 
altered sleep–wake cycles.
• Hearing decline may be associated with 
increased vocalization.
• Cognitive dysfunction syndrome (CDS) 
can lead to sleep disturbances, anxiety, and 
excessive vocalization.
• Night waking may be due to a change in 
schedule, environment, or activity, especially 
in senior pets that are more sensitive to 
change.
• Diseases of other systems may cause or 
contribute to signs.
GENETICS
N/A
Unknown
Species
• Asian breeds of cats may be prone to excess 
vocalization.
• Working and hunting breeds may be more 
prone to barking.
• Puppies may not be able to sleep 
through the night without waking to 
eliminate.
• Senior pets may be more prone to 
vocalization and night waking due to 
Intact females during estrus and mating.SIGNS
• Vocalization at times or in intensity that 
disturbs owners or neighbors.
• Sleeping pattern altered—does not fall 
asleep at bedtime, awakens during the night, 
or sleeps more during the day.
• Signs reported vary with how disruptive 
they are to the family, neighbors, and the pet’s 
quality of life.
• Pets with CDS may pace, wander aimlessly, 
have decreased interest in social interactions, 
be less responsive to stimuli and increasingly 
anxious.
• Additional signs related to medical causes.
Signs associated with underlying medical 
issues.
CAUSES
• Vocalization and night waking—medical: 
gastrointestinal, metabolic (renal, hepatic), 
urogenital, CNS disorders, CDS, hypertension, 
hyperadrenocorticism or hypothyroidism (dog), 
hyperthyroidism (cat), pain, sensory decline.
• Vocalization:
◦ Anxiety or conflict.
◦ Normal for individual or breed.
◦ Alarm barking—response to novel 
stimuli.
◦ Territorial—warning or guarding.
◦ Owner inadvertently reinforces.
◦ Also reinforced each time stimulus retreats.
◦ Distress vocalization, e.g., howl or whine 
may be related to separation from social 
group.
◦ Growl—associated with agonistic displays.
◦ Stereotypic behaviors—dog.
◦ Mating/sexual—cat.
• Night waking:
◦ Normal crepuscular rhythm—cat.
◦ Changes in routine and/or environment—  
insufficient enrichment/scheduling.
◦ Hyperactivity/hyperkinesis—dog.
• Increasing age.
• Changes in schedule or environment.
  DIAGNOSIS
Sleep disorders.
To determine if underlying medical cause.
• T4 and blood pressure—senior cats.
• Rule out hypothyroidism and hyperadreno-
corticism in dogs.IMAGING
To rule out medical/neurologic if indicated.
• Behavioral diagnosis based on history; 
observation of pet, owner, and their interactions; 
video if available.
• Intraocular pressure.
(BAER) if indicated to rule out auditory 
decline.
• Endoscopy and biopsy if gastrointestinal 
cause suspected.
N/A
  TREATMENT
If any medical issues.
ACTIVITY
Insure behavioral needs (e.g., social inter  - 
actions, exercise, elimination, routine, and 
mental stimulation) are adequately met 
each day.
 DIET
• Feed from toys to encourage normal 
hunting and scavenging behaviors.
• Timed feeders and multiple small meals.
Individualize for the pet, home, and 
problem.
• Identify and minimize or avoid exposure to 
inciting stimuli.
• Provide a quiet and calm environment for 
security, rest, and sleep.
• Structure all interactions (i.e., calm sit or 
down and quiet behavior for all rewards).
• Reward-based training to teach calm/settle 
on cue (“Sit,” “Down,” “Mat”).
• Response substitution—use settle  commands 
to train alternative acceptable behavior.
• Head halter may provide more immediate 
control to quiet and calm.
• Eliminate any owner reinforcement.
• Owner anxiety, verbal reprimands, and 
punishment may increase anxiety and 
potentiate barking.
• Desensitize and countercondition—
expose the pet to the inciting stimulus at a 
low level (under the response threshold) and 
pair a favored reward (e.g., food treat) with 
each exposure to change the emotional 
response. Gradually progress to more 
intense stimulus.
• Interrupting vocalization by directing into 
an alternative behavior may help to achieve

Canine and Feline, Seventh Edition  477
Equiet, which can then be reinforced; however, 
aversive techniques may increase anxiety.
Environmental Modification
Modify environment to avoid or minimize 
exposure to stimuli that incite vocalization 
or wake the pet, e.g., covered crate, quiet 
room, thunder cap, classical music, white 
noise or fan.
N/A
• Short term or as needed for situations of 
anxiety or for inducing sleep.
• Benzodiazepines—dog: clonazepam 
0.05–0.25 mg/kg, diazepam 0.5–2.2 mg/kg; 
cat: oxazepam 0.2–0.5 mg/kg, alprazolam 
0.125–0.25 mg/cat, clonazepam 0.02–
0.2 mg/kg.
• T razodone—dog: 5–10 mg/kg; cat: 
25–50 mg/cat.
• Gabapentin—dog: 20–30 mg/kg; cat: 
50–100 mg/cat.
• Melatonin—dog and cat: 3–6 mg 
(1.5–12 mg).
• For ongoing therapy for chronic anxiety or 
compulsive disorders—clomipramine 
(tricyclic antidepressant [TCA]): dog: 
1–3 mg/kg PO q12h, cat: 0.5–1 mg/kg PO 
q24h; fluoxetine or paroxetine (selective 
serotonin reuptake inhibitors [SSRIs]): dog: 
1–2 mg/kg PO q24h, cat: 0.5–1.5 mg/kg PO 
q24h.
• Natural products that might be used 
adjunctively for anxiety—Adaptil®, Feliway®, 
l-theanine, alpha-casozepine, Harmonease®, 
S-adenosyl-L-methionine-tosylate disulfate 
(SAMe), or aromatherapy (lavender).
• For CDS—selegiline and cognitive 
supplements (see Cognitive Dysfunction 
Review contraindications and side effects for 
each drug used.
• Caution with drugs that might sedate in 
elderly pets.• Monitor for undesirable behavioral effects.
• Avoid anticholinergic drugs in pets with 
CDS.
Do not use SSRIs and TCAs together with 
monoamine oxide (MAO) inhibitors such 
as selegiline and amitraz, and use  cautiously 
or avoid with buspirone and tramadol.
• Concurrent sedation with acepromazine 
0.5–2.2 mg/kg might be considered, but it is 
not anxiolytic and may increase noise 
sensitivity and vocalization.
• For a less sedating anxiolytic consider 
buspirone at 0.5–1 mg/kg (dogs: q8–12h; 
cats: q12h).
• Analgesics for pain control.
  FOLLOW-UP
Modify the program based on response to 
therapy.
• T rain calm and settle on cue (sit, down, go 
to mat).
• Predictable interactions, e.g., insure calm sit 
or down and quiet before any reward given.
• Reward desirable, do not punish  undesir  - 
able behavior.
• Socialize and habituate pet when young to a 
wide range of people, pets, stimuli, and 
• Provide enrichment to meet needs 
including food puzzles and multiple small 
meals for cats.
• Night-time waking can lead to fatigue, 
increased irritability, and possibly aggression.
• Both night waking and vocalization can be 
particularly distressing to the pet owner’s 
health and wellbeing and greatly weaken the 
bond.
• Variable—based on diagnosis, environment, 
pet, and owner expectations.
• Most can be improved over time, but might 
not be eliminated.  MISCELLANEOUS
CDS
Increased anxiety and night waking more 
common in senior pets.
None, but sleep disruption and anxiety in 
pets can contribute to sleep disruption and 
anxiety in owners.
N/A
SYNONYMS
Sleep disturbances.
SEE ALSO
response.
• CDS = cognitive dysfunction syndrome.
• MAO = monoamine oxide.
Landsberg GM, DePorter T, Araujo JA. 
Management of anxiety, sleeplessness and 
cognitive dysfunction in the senior pet. Vet 
41(3):565–590.
Horwitz DF (ed.). Blackwell’s Five-Minute 
Canine and Feline Behavior, 2nd ed. 
Hoboken: NJ: Wiley, 2018, pp. 885–894.
Authors  Sagi Denenberg and Gary M. 
Landsberg
Consulting Editor  Gary M. Landsberg(continued)  Excessive Vocalization and Waking at Night—Dogs and Cats

478  Blackwell’s Five-Minute Veterinary Consult  
E  BASICS
Inherited nervous system disorder causing 
weakness and collapse during intensive 
exercise in otherwise normal Labrador 
retrievers and a few other breeds.
• Labrador retrievers—approximately 6% of 
all pet, show, and field Labrador retrievers are 
affected.
• Also occurs in Chesapeake Bay retrievers, 
curly-coated retrievers, and Boykin spaniels, 
and rarely in Old English sheepdogs, German 
wirehaired pointers, Bouvier des Flandres, 
Pembroke Welsh corgis, and cocker spaniels.
• No sex or color predilection.
SIGNS
• No systemic signs.
• Episodes of collapse first occur between  
5 months and 3 years of age.
• Collapse episodes occur only with extremes 
of exciting exercise.
• Dogs can engage normally in hiking, 
swimming, jogging, and other activities.
Between weakness/collapse episodes, physical 
and neurologic examinations are normal.
Features of Weakness/Collapse 
Episodes
• Weakness occurs after 5–20 minutes of 
intense exercise with excitement or stress.
• Rear limbs become weak and unable to 
support weight.
• Rear limb muscles are flaccid during 
collapse and there is a loss of patellar reflexes.
• Dogs may continue to run, dragging their 
rear limbs in a crouched posture.
• During a severe episode, all four limbs can be 
affected; rarely the dog may become recumbent 
and unable to move its limbs or raise its head.
• Dogs remain conscious and fully alert 
during episodes.
• There is no apparent pain or discomfort on 
palpation or manipulation of the muscles, 
joints, or spine during or after collapse.
• Complete recovery occurs within 5–30 
minutes.
• Rectal temperature is elevated (mean 
>107 °F; >41.6 °C), but not different from 
Labradors without exercise-induced collapse 
doing similar exercise.
• A few dogs with exercise-induced collapse 
(EIC) have died during collapse—death is 
usually preceded by a short generalized 
seizure. The cause of death is uncertain, but 
weakness of the respiratory muscles and 
extreme hyperthermia are suspected.CAUSES
• Genetic disorder—inherited as an 
autosomal recessive trait.
• Symptomatic dogs are homozygous for a 
mutation in the dynamin 1 gene. Dynamin 1 
(DNM1 ) is a protein important in neuro-
transmission in the brain and spinal cord 
during high-level neuronal activity. There is 
evidence that the DNM1  mutation associated 
with EIC has its most profound effect on 
DNM1  function when body temperature is 
elevated, as normally occurs with exercise.
• Genetically affected dogs are at risk for 
collapse when participating in high-intensity 
exercise with concurrent excitement or stress.
• T rigger activities most likely to induce collapse 
include repetitive fun or training retrieves, upland 
bird hunting, intense play with other dogs, and 
running alongside an all-terrain vehicle.
• Increased ambient temperature and 
humidity increase the risk of collapse in 
affected dogs.
• Most genetically affected dogs ( >80%) will 
have at least one episode of collapse before 
they reach 3 years of age, but affected dogs 
with a sedentary lifestyle or calm temperament 
may never exhibit weakness or collapse.
  DIAGNOSIS
• The episodic nature of the collapse, 
association with exercise and excitement, 
typical features of collapse including rear 
limb weakness and normal mentation, 
progression of weakness during an episode, 
and rapid complete recovery should lead to a 
presumptive diagnosis of EIC in an otherwise 
healthy Labrador retriever. Physical and 
neurologic examinations are normal; further 
evaluation should be performed to eliminate 
other causes of weakness and collapse. 
Genetic testing is required to confirm the 
diagnosis of EIC.
• The disorder most often confused with EIC 
is a focal seizure/movement disorder 
characterized by brief episodes of abnormal 
crouched gait, disequilibrium, head-bobbing, 
or incoordination. Episodes are often induced 
by exercise/excitement, leading to confusion 
with EIC. The onset of signs is peracute, the 
episodes are short (usually less than 5 
minutes), all limbs are involved, and recovery 
is immediate, helping to distinguish this 
disorder from the more progressive gait 
disturbance caused by EIC. Diagnosis can 
only be made by ruling out other disorders 
(including EIC) with testing.
• Dogs with metabolic myopathies, 
polymyositis, and myasthenia gravis are 
typically much more exercise intolerant than dogs with EIC and they collapse with mild 
exercise of short duration.
• Centronuclear myopathy—inherited 
muscle disorder in Labrador retrievers that 
causes generalized muscle atrophy, constant 
weakness that worsens with exercise, and 
absent patellar reflexes at rest. Diagnosis of 
this disorder is by muscle biopsy or DNA 
testing (http://labradorcnm.vet-alfort.fr/
pages/site/Overview_history.html).
• Cardiac arrhythmia—as a cause of exercise 
intolerance can be ruled out by cardiac 
auscultation, palpation of femoral pulses, and 
performing an ECG at rest and during 
collapse. Holter monitor or an ECG event 
recorder may be required to rule out 
intermittent cardiac arrhythmia.
• Pulmonary hypertension—can cause exercise 
intolerance and syncopal episodes as exercise 
and excitement increase systolic pressure in an 
already overloaded right ventricle and pulmo -
nary arteries, resulting in reflex bradycardia, 
vasodilation, and hypotension.
• Hypoglycemia—ruled out by measuring 
blood glucose during an episode.
• Hypo- or hyperkalemia—ruled out by 
measuring potassium during collapse.
• Hypoadrenocorticism (Addison’s disease)—
can cause exercise-induced hypoglycemic 
collapse or seizures; should be ruled out with 
adrenocorticotropin hormone (ACTH) 
• Cataplexy—peracute, nonprogressive, brief 
episodes of flaccid paralysis.
• Heat stroke—collapse due to heat stroke is 
usually associated with bleeding, shock, and 
abnormal mentation. Acute renal failure, 
disseminated intravascular coagulation (DIC), 
and death are common. Recovery, if it does 
occur, is prolonged.
• Malignant hyperthermia—hypermetabolic 
state triggered by certain anesthetics, extreme 
heat, intense activity, or psychologic stress in 
genetically susceptible dogs. Hyperthermia, 
generalized skeletal muscle contraction, 
rhabdomyolysis, and DIC occur and many 
dogs die. Recovery, if it does occur, is 
prolonged. In vitro contracture tests on 
muscle biopsies or identification of the 
causative genetic mutation of the ryanodine 
receptor ( RYR1 ) is required for diagnosis.
Normal at rest and during collapse.
• Arterial blood gas—normal at rest, 
respiratory alkalosis and metabolic acidosis 
during collapse identical to intensively 
exercising Labradors without EIC.
• Lactate and pyruvate—normal at rest, not 
different during collapse from exercising 
Labradors without EIC.
• Thyroid evaluation—normal.
• ACTH stimulation test—normal.Exercise-Induced Weakness/Collapse in Labrador Retrievers

Canine and Feline, Seventh Edition  479
E• Analysis for mutation in RYR1  causing 
malignant hyperthermia—negative.
• Testing for acetylcholine receptor 
antibodies causing acquired myasthenia 
gravis— negative.
IMAGING
Thoracic and abdominal radiographs, abdominal 
ultrasound, echocardiography—normal.
ECG findings at rest and during collapse— 
normal.
DNA Testing
• Definitive diagnosis requires demonstration 
that a dog has two copies of the causative 
DNM1  mutation.
• Testing can be performed on blood, cheek 
swabs, puppy dewclaws, or semen.
• Approximately 6% of all tested Labrador 
retrievers have two copies of the DNM1  
mutation (affected); >35% of all tested 
Labrador retrievers have one copy of the 
DNM1  mutation (carrier).
• Finding two copies of the DNM1  mutation 
confirms that a dog is EIC affected and 
susceptible to collapse, but does not rule out 
other causes of exercise intolerance or 
collapse. It is important to do the necessary 
tests to rule out other causes of collapse that 
may be potentially more treatable.
• Muscle histology—normal.
• Complete postmortem examinations of dogs 
dying during collapse due to EIC—normal.
  TREATMENT
ACTIVITY
Most affected dogs can live normal active lives 
if specific trigger activities are avoided or 
done in moderation.CLIENT EDUCATION
• Signs commonly worsen in the 3–5 minutes 
after exercise is terminated; some ( <5%) 
affected dogs die during collapse.
• All activity should be halted at the first sign 
of weakness or incoordination.
• Consider offering cool water orally, spraying 
with water, or immersing in water to lower 
body temperature.
There is no recommended drug therapy for 
this disorder.
  FOLLOW-UP
Most affected dogs can be managed effectively 
by avoiding trigger activities and carefully 
observing for the first signs of weakness.
Dogs with EIC do not develop other 
associated medical conditions as they age.
Episodes of collapse may become less  
frequent as dogs age, perhaps because 
of less excitement associated with trigger 
activities.
• Animals should be tested to establish their 
EIC status prior to breeding.
• Affected dogs (with two copies of the 
DNM1  mutation) should not be bred or should be bred only to known 
noncarriers to avoid producing affected 
• Carrier dogs (with one copy of the DNM1  
mutation) should only be bred to known 
• EIC = exercise-induced collapse.
https://www.vetmed.umn.edu/research/labs/
canine-genetics-lab/genetic-testing/
exercise-induced-collapse
Furrow E, Minor KM, Taylor SM, et al. 
Relationship between Dynamin-1 mutation 
status and phenotype in 109 Labrador 
retrievers with recurrent collapse during 
exercise. J Am Vet Med Assoc 2013, 
242:786–791.
Patterson EE, Minor KM, Tchernatynskaia 
AV, et al. A canine DNM1 mutation is 
highly associated with the syndrome of 
exercise-induced collapse. Nat Genet 2008, 
40(10):1235–1239.
Taylor SM, Shmon CL, Adams VJ, et al. 
Evaluations of Labrador retrievers with 
exercise-induced collapse, including 
response to a standardized strenuous 
exercise protocol. J Am Anim Hosp Assoc 
2009, 45:3–13.
Taylor SM, Shmon CL, Shelton GD, et al. 
Exercise induced collapse of Labrador 
retrievers: survey results and preliminary 
investigation of heritability. J Am Animal 
Hosp Assoc 2008, 44:295–301.
Author  Susan M. Taylor(continued)  Exercise-Induced Weakness/Collapse in Labrador Retrievers

480  Blackwell’s Five-Minute Veterinary Consult  
EExocrine Pancreatic Insufficiency
  BASICS
Syndrome that is caused by inadequate 
amounts of pancreatic digestive enzymes in 
the small intestinal lumen.
• Most commonly caused by insufficient 
synthesis and secretion of pancreatic enzymes 
by the exocrine pancreas. •  In rare cases can 
be caused by an obstruction of the pancreatic 
duct or isolated lipase deficiency. 
• Insufficient synthesis of pancreatic digestive 
enzymes can be due to destruction of acinar 
cells resulting from chronic pancreatitis 
(approximately 50% of cases in dogs and 
almost all cases in cats) or can be due to 
idiopathic pancreatic acinar atrophy (PAA; 
most common cause of exocrine pancreatic 
insufficiency in German shepherd dogs). 
• Deficient exocrine pancreatic secretion 
results in maldigestion and nutrient malab-
sorption, leading to weight loss and loose 
stools with steatorrhea. •  Malabsorption 
contributes to small intestinal dysbiosis.
Nutritional—protein-calorie malnourish- 
ment.
GENETICS
Assumed to be hereditary in the German 
shepherd dog and probably transmitted by a 
complex trait (early studies have suggested an 
autosomal recessive trait, but this is no longer 
believed to be the case).
• PAA is very commonly seen in the German 
shepherd dog; it is less commonly seen in 
rough-coated collies and Eurasians. •  Other 
causes of exocrine pancreatic insufficiency 
(EPI) may be seen in all dog and cat breeds. 
• Less common in cats than in dogs.
None
Species
German shepherd dogs, rough-coated collies, 
and Eurasians.
• PAA in young adult dogs. •  Chronic 
pancreatitis in dogs and cats of any age.
SIGNS
• Consider in young adult (age range approx- 
imately 1–4 years) German shepherd dogs with weight loss and loose stools. 
• Severity—varies depending on time until 
diagnosis and therapy.
• Weight loss with normal to increased 
appetite. •  Chronically loose stools or 
diarrhea. •  Fecal volumes are larger than 
normal and may be associated with steator-
rhea. •  Flatulence and borborygmus are 
commonly reported, especially in dogs. 
• May show coprophagia and/or pica. •  May 
be accompanied by polyuria/polydipsia with 
diabetes mellitus as a sequel to chronic 
• Thin body condition. •  Decreased muscle 
mass. •  Poor-quality hair coat. •  Cats with 
steatorrhea may have greasy “soiling” of the 
hair coat in the perineal area, but this is seen 
in the minority of cases.
CAUSES
• PAA. •  Chronic pancreatitis. •  Pancreatic 
adenocarcinoma or other abdominal tumor 
leading to pancreatic duct obstruction
• Breed—German shepherd dogs, rough-
coated collies, and Eurasians. •  Any 
condition predisposing dogs or cats to chronic 
  DIAGNOSIS
• Secondary causes of chronic diarrhea and 
weight loss (e.g., hepatic failure, renal failure, 
hypoadrenocorticism, and hyperthyroidism in 
cats). •  Primary gastrointestinal disease (e.g., 
infectious, inflammatory, neoplastic, 
mechanical, or toxic).
Direct/Indirect Fecal Examinations
Negative for parasites.
Exocrine Pancreatic Function Tests—
Trypsin-Like Immunoreactivity (TLI)
• Diagnostic test of choice in both dogs and 
cats. •  Principle of test—serum TLI can be 
measured by an assay that detects trypsinogen 
and trypsin that is directly released into the 
blood from pancreatic acinar cells; serum TLI 
is detected in the serum of all normal dogs and 
cats with a functional exocrine pancreatic mass. 
• Serum TLI concentrations are dramatically 
reduced with EPI—dogs: cTLI ≤2.5  μg/L; 
cats: fTLI ≤8.0  μg/L. •  The TLI tests are 
species specific. •  Advantages—simple; quick; 
single serum specimen (fasted); highly sensitive 
and specific for EPI in both species.Other Exocrine Pancreatic Function 
Tests
• Assays of fecal proteolytic activity using 
casein-based substrates have been used to 
diagnose EPI in both dogs and cats; however, 
fecal proteolytic activity is associated with 
false-positive and false-  negative test results 
and should only be used in exotic species for 
which a serum TLI test is not available. •  An 
assay for the measurement of fecal elastase has 
been validated for the dog; however, this test 
is associated with a high rate of false-positive 
test results; therefore a positive test result, 
suggesting EPI, must be verified by measure-
ment of a serum cTLI concentration.
Screening Tests for Malassimilation
Microscopic examination of feces for 
undigested food, assessment of fecal proteo  - 
lytic activity, and the plasma turbidity test are 
unreliable and not recommended.
Cobalamin and Folate
• Often run as a panel with TLI. •  Used to assess 
for concurrent small intestinal dysbiosis or 
concurrent small intestinal disease (such as 
inflammatory bowel disease [IBD]). •  Cobalamin 
(vitamin B12) is frequently deficient in both dogs 
and cats with EPI and can lead to treatment 
failure or complications if not addressed.
IMAGING
Abdominal radiography and ultrasonography 
are unremarkable unless the patient has 
concurrent conditions.
N/A
• Chronic pancreatitis—microscopically, acini and 
possibly islets are depleted and replaced by fibrous 
tissue; there may also be an active inflamma-
tory infiltration. •  PAA—marked atrophy/
absence of pancreatic acinar tissue on gross 
and histopathologic inspection in dogs with PAA.
  TREATMENT
• Outpatient medical management. 
• Patients with concurrent diabetes mellitus 
may initially require hospitalization if ill (e.g., 
diabetic ketoacidosis).
N/A
ACTIVITY
No restriction.
DIET
• Type of diet does not play a role in the 
management of EPI in dogs and cats. 
• However, low-fat and high-fiber diets 

Canine and Feline, Seventh Edition  481
• Discuss hereditary nature in German shepherd 
dogs. •  Discuss expense of pancreatic enzyme 
supplementation and need for lifelong therapy. 
• Discuss the possibility of diabetes mellitus in 
patients with chronic pancreatitis.
Mesenteric torsion has been reported in 
German shepherd dogs with EPI in Finland, 
but not North America.
• Powdered pancreatic enzymes are the treat  - 
ment of choice (as a reference these products 
should contain at least 70,000 USP of lipase per 
teaspoon). •  In Europe, microencapsulated 
products are available; because the lipase is 
protected from gastric inactivation a much 
smaller amount is needed for treatment. 
• Initially—mix enzyme powder in food at a 
dosage of 1 teaspoon/10 kg body weight with 
each meal; feed at least two meals daily to 
promote weight gain. •  Preincubation of 
enzymes with food does not improve the 
effectiveness of oral enzyme therapy, but may 
negatively impact owner compliance. 
• Approximately 85% of all dogs with EPI and 
virtually all cats with EPI are cobalamin deficient 
and require parenteral or oral cobalamin 
supplementation (see Cobalamin Deficiency for 
dosing). •  Administration of a proton pump 
inhibitor (e.g., omeprazole at 0.7–1.0 mg/kg 
q12h) may improve the condition in nonrespon -
sive patients. •  Most dogs and cats respond to 
therapy within 5–7 days; after a complete 
response has been achieved, the amount of 
pancreatic enzyme supplement may be gradually 
reduced to a dose that prevents return of clinical 
signs. •  Oral antibiotic therapy (tylosin: 25 mg/
kg PO q12h) may be required for 4–6 weeks in 
patients with concurrent dysbiosis, but in most 
patients dysbiosis resolves spontaneously upon 
commencement of enzyme replacement therapy. 
• Severely malnourished dogs may also require 
supplementation with tocopherol; body stores of 
other fat-soluble vitamins are probably also 
decreased in dogs and cats with EPI, but 
supplementation does not appear to be crucial.
Avoid tablets and capsules, as mixing of 
enzymes and chyme is unpredictable.
N/A
N/A
• The cost of pancreatic enzyme  replacement is 
very high; also, some cats refuse to consume the 
pancreatic enzyme supplement; these patients can often be successfully managed by addition of 
fish oil to the enzyme supplement or administra -
tion of raw beef, pork, or game pancreas. •  Each 
teaspoon of pancreatic enzyme supplement 
needs to be replaced with 1–3 ounces (approxi -
mately 30–90 g) of raw chopped pancreas. 
• Raw pancreas can be kept frozen for months 
without losing enzymatic activity.
  FOLLOW-UP
• Weekly for first month of therapy. 
• Diarrhea improves markedly—fecal 
consistency typically normalizes within 1 
week. •  Gain in bodyweight. •  Patients that 
fail to respond after 2 weeks of enzyme 
therapy and cobalamin supplemenation 
should be treated for secondary intestinal 
dysbiosis. •  Once bodyweight and condition 
normalize, gradually reduce daily dosage of 
enzyme supplements to a level that maintains 
normal fecal quality and bodyweight.
Do not breed patients that belong to a breed 
predisposed to PAA.
• Approximately 20% of dogs fail to respond 
to pancreatic enzymes and need further 
evaluation and therapy. •  Most patients with 
EPI have cobalamin deficiency and need to be 
managed accordingly. •  Some dogs and cats 
treated with pancreatic enzyme supplements 
develop oral ulcerations; in most of these 
patients the dose of pancreatic enzyme 
supplements can be decreased, while maintain -
ing therapeutic response; in a few patients, the 
dose of the pancreatic enzyme supplement 
needs to be adjusted frequently to avoid 
treatment failure and oral ulceration. •  T wo 
cats with EPI and vitamin K–responsive 
coagulopathy have been reported; thus, patients 
that present with a bleeding diathesis should be 
further evaluated and possibly treated with 
parenteral vitamin K supplementation.
• Most causes are irreversible, and lifelong 
therapy is required. •  Patients with EPI alone 
have a good prognosis with appropriate enzyme 
supplementation and supportive management. 
• Prognosis is more guarded in patients with 
EPI and concurrent diabetes mellitus.
• Dysbiosis. •  Cobalamin deficiency. •  IBD. 
• Diabetes mellitus. •  Associated vitamin 
K–responsive coagulopathy.AGE-RELATED FACTORS
Consider EPI in young adult German shepherd 
dogs with weight loss and loose stools.
None
Do not breed animals with EPI suspected to 
be due to PAA.
SYNONYMS
None
SEE ALSO
• Cobalamin Deficiency.
• Diarrhea, Chronic—Cats. 
• Diarrhea, Chronic—Dogs. 
• Pancreatitis—Cats. 
• cTLI = canine trypsin-like immunoreactivity.
• fTLI = feline trypsin-like immunoreactivity. 
• PAA = pancreatic acinar atrophy.
• TLI = trypsin-like immunoreactivity.
http://www.vetmed.tamu.edu/gilab
Batchelor DJ, Noble PJ, Taylor RH, et al. 
is likely if clinical remission is achieved. J 
Vet Intern Med 2007, 21:54–60.
German AJ. Exocrine pancreatic insufficiency 
in the dog: breed associations, nutritional 
considerations, and long-term outcome. 
Top Companion Anim Med 2012, 
27:104–108.
Steiner JM. Exocrine pancreas. In: Steiner 
JM, ed., Small Animal Gastroenterology. 
Hanover: Schlütersche-Verlagsgesellschaft, 
2008, pp. 283–306.
Thompson KA, Parnell NK, Hohenhaus AE, 
et al. Feline exocrine pancreatic insuffi-
ciency: 16 cases (1992–2007). J Feline Med 
Surg 2009, 11:935–940.
Westermarck E, Wiberg M. Exocrine 
pancreatic insufficiency in the dog: 
historical background, diagnosis, and 
treatment. Top Companion Anim Med 
2012, 27:96–103.
Xenoulis PG, Zoran DL, Fosgate GT, et al. 
Feline exocrine pancreatic insufficiency: a 
retrospective study of 150 cases. J Vet Intern 
Med 2016, 30:1790–1797.
Consu lting Editor  Mark P . Rondeau
available online(continued)  Exocrine Pancreatic Insufficiency

482  Blackwell’s Five-Minute Veterinary Consult  
EEyelash Disorders (Trichiasis/Distichiasis/Ectopic Cilia)
  BASICS
OVERVIEW
• T richiasis—normal hair from the skin 
contacting corneal or conjunctival surface. 
• Distichiasis—abnormal hairs that emerge 
from the meibomian glands along the eyelid 
margin; may contact corneal or conjunctival 
surface. • Ectopic cilia—abnormal hairs that 
emerge through the palpebral conjunctiva 
several millimeters from the lid margin; 
contact the corneal surface.
• Trichiasis : ◦ Facial fold trichiasis—  
brachycephalic dogs with prominent facial 
folds or a shallow orbit and prominent globe 
(e.g., Pekingese, pug, English bulldog). 
◦ Entropion—rolling in of eyelid margin; 
conformational (primary) entropion common 
in young dogs in predisposed breeds (shar pei, 
retrievers, chow chow, English bulldog, 
among others); secondary (acquired) 
entropion may occur in dogs and cats of any 
breed or age. ◦ Eyelid agenesis (eyelid 
coloboma)—congenital in cats; sporadic 
occurrence. • Distichiasis — common in 
young dogs; rare in cats; some predisposed 
breeds include spaniels, English bulldog, 
flat-coated retriever, and dachshund. • Ectopic 
cilia—common in young dogs, rare in cats; 
predisposed breeds include Pekingese, shih 
tzu, and English bulldog.
SIGNS
Facial-Fold Trichiasis
• Commonly bilateral. • Epiphora. 
• Pigmentary keratitis (especially nasally). 
• Often associated with lagophthalmos 
(incomplete blink). • Blepharospasm if 
ulcerative keratitis present.
Trichiasis Associated with Entropion
• Bilateral if primary. • Blepharospasm. 
• Epiphora. • Conjunctivitis. • Keratitis 
(vascularization, pigmentation, possibly 
ulcerative).
Eyelid Agenesis
• Typically bilateral. • Absent portion of 
dorsal-lateral eyelid margin. • Other 
intraocular congenital abnormalities are 
common. • Conjunctivitis. • Keratitis 
(vascularization, pigmentation; possibly 
ulcerative). • Lagophthalmos. 
• Blepharospasm.
Distichiasis
• Involves upper and/or lower eyelid margin; 
unilateral or bilateral. • Soft hairs and those 
directed away from the cornea: asymptomatic. 
• Stiff, stout cilia contacting the cornea: 
blepharospasm, epiphora, conjunctivitis, and 
keratitis (vascularization, pigmentation; 
possibly ulcerative).Ectopic Cilia
• Unilateral or bilateral; typically central/
upper eyelid. • Hair may be pigmented or 
nonpigmented. • Severe blepharospasm. 
• Epiphora. • Conjunctivitis. • Recurrent 
superficial corneal ulcers.
• T richiasis—often related to conformation. 
• Secondary (acquired) entropion may be 
associated with pain (spastic entropion), 
scarring (cicatricial entropion), or 
 enophthalmos; occasionally seen in cats. 
• Distichiasis—considered to be inherited; 
many predisposed breeds. • Eyelid agenesis 
(eyelid coloboma)—may be hereditable or 
due to in utero viral infection. • Ectopic 
cilia—multiple breeds predisposed.
  DIAGNOSIS
• Other adnexal abnormalities. 
• Keratoconjunctivitis sicca. • Conjunctival 
foreign body. • Infectious or inflammatory 
conjunctivitis. • Diagnosis based on observation 
of abnormal cilia and lid/facial conformation.
N/A
N/A
IMAGING
N/A
Ocular examination with magnification.
  TREATMENT
Trichiasis
• Conservative management—topical lubricating 
ointments. • Clipping hair on facial folds may 
cause hairs to become stiffer and more irritating. 
• Surgical correction of adnexal abnormalities 
(primary entropion, eyelid agenesis). • Reduce/
remove facial folds in contact with ocular surface. 
• Medial  canthoplasty—for nasal trichiasis; 
reduces lagophthalmos and medial entropion. 
• T reat underlying cause (e.g., spastic entropion, 
enophthalmia); temporary eyelid tacking may be 
• If asymptomatic, no treatment is required. 
• Symptomatic—mechanical removal 
(periodic manual epilation) or surgical 
destruction of hair follicles by cryoepilation, 
electroepilation, or transconjunctival electro -
cautery. • Avoid lid-splitting and partial tarsal 
plate excision techniques; may predispose to 
cicatricial entropion and impaired lid function.Ectopic Cilia
• Surgical treatment—en bloc resection of 
the cilia and associated meibomian gland. 
• Cryotherapy—may be used as sole treat- 
ment or adjunct after resection. • May 
develop ectopic cilia at other locations. 
• Recheck if clinical signs recur.
• Rarely indicated. • Lubricant ointments—
lessen irritation before surgical correction. 
• Soft contact lens—temporary relief of 
clinical signs before surgical correction. 
• Topical antibiotics—for ulcerative keratitis, 
prophylactic following surgical eyelid 
N/A
  FOLLOW-UP
• T richiasis—good prognosis; some corneal 
changes may be permanent. • Distichiasis—
regrowth may occur; destructive procedures 
must be done conservatively to minimize lid 
damage. • Ectopic cilia—good prognosis; 
regrowth may occur.
Bettenay S, Mueller RS, Maggs DJ. Diseases 
of the eyelids. In: Maggs DJ, Miller PE, 
Ofri R, Slatter’s Fundamentals of Veterinary 
Gelatt KN, Plummer CE. Canine eyelids. In: 
Gelatt KN, Plummer CE, eds., Color Atlas 
of Veterinary Ophthalmology, 2nd ed. 
Wiley-Blackwell, 2017, pp. 67–85.
Author  Renee T. Carter
Filipe Espinheira.

Canine and Feline, Seventh Edition  483
FFacial Nerve Paresis and Paralysis
  BASICS
Dysfunction of the facial nerve (cranial nerve 
[CN] VII) causing paresis (weakness) or 
paralysis of the muscles of facial expression, 
which include the ears, eyelids, lips, and nostrils.
• Central—impairment of the facial nucleus 
within the rostral medulla (brainstem).
• Peripheral—impairment of the facial nerve 
anywhere along its length or at the 
neuromuscular junction.
• Nervous—facial nerve peripherally or its 
nucleus centrally.
• Ophthalmic—if parasympathetic 
preganglionic neurons that supply the 
lacrimal gland and gland of the third eyelid 
that course with the facial nerve proximally 
are affected, keratoconjunctivitis sicca (KCS) 
develops due to lack of tear secretion.
GENETICS
N/A
More common in dogs than cats.
Species
Idiopathic paralysis—cocker spaniel, beagle, 
Pembroke Welsh corgi, boxer, English setter, 
golden retriever, and domestic longhair cats.
Adults
N/A
SIGNS
• Assess strength of palpebral closure—there 
should be full eyelid closure when a finger is 
gently passed over the eyelids.
• Idiopathic—unaffected side may become 
affected within a few weeks to months; may 
rarely occur bilaterally at first presentation; 
can have concurrent idiopathic vestibular 
neuropathy.
• Most patients with bilateral nerve 
involvement have polyneuropathy-associated 
systemic disease—look for other nerve deficits.
• May accompany other clinical signs and/or 
neurologic deficits—always perform a full 
neurologic examination.
• Ear droop is not always evident in cats and 
dogs with erect ears.
• Messy eating; food left around mouth.
• Excessive drooling on affected side.• Facial asymmetry.
• Eye—inability to close eyelids, rubbing, 
ocular discharge, ulceration.
• Facial asymmetry—lip and ear droop, wide 
palpebral fissure, collapse of nostril.
• Decreased or absent palpebral reflex.
• Decreased or absent menace response (may 
see eye retraction rather than lid closure).
• Inability to close eyelids.
• Excessive drooling or food falling from 
mouth on affected side.
• Chronically, patients may have facial 
muscle contraction toward the affected side 
due to muscle fibrosis subsequent to paralysis 
and denervation.
• Decreased Schirmer tear test, mucopurulent 
discharge from affected eye, and exposure 
conjunctivitis or keratitis with concurrent 
KCS.
• Altered mentation (e.g., somnolence or 
stupor) and/or other cranial nerve 
abnormalities and gait disturbances may be 
noted when secondary to intracranial 
(brainstem) disease.
• Hemifacial spasms (facial nerve tetanus) 
may be infrequently observed in lesions 
affecting the facial nerve such as neuritis or 
otitis media. These patients have sustained 
contraction of the facial muscles, giving a 
“grinning” appearance to the affected side of 
the face. This is a dynamic process and at 
times the face will appear normal, only to 
begin the “grinning” appearance once again. If 
one notices this clinical presentation, middle 
ear disease should be investigated thoroughly.
• Intermittent facial paresis can be observed 
in patients with a contralateral thalamocortical 
lesion when patient is relaxed—due to 
“release” of upper motor neuron influence on 
lower motor neuron (CN VII).
• Concurrent heat tilt on ipsilateral side with 
concurrent otitis interna.
• Concurrent head tilt on ipsilateral side 
with concurrent idiopathic vestibular 
• Abnormal tympanum (bulging, opaque, 
rupture) on otoscopic examination. Obvious 
external ear disease may not be present with 
CAUSES
Unilateral Peripheral
• Infectious—otitis media–interna (dogs and 
cats).
• Inflammatory—nasopharyngeal polyps 
(cats), neuritis.
• Iatrogenic—secondary to surgical ablation 
of external ear canal or bulla osteotomy; 
secondary to exuberant ear cleaning; 
idiosyncratic reaction to potentiated 
sulfonamides (dogs).• Neoplastic—aural cholesteatoma, squamous 
• T rauma—fracture of petrous temporal bone, 
direct injury to facial nerve by laceration, or 
compression by hematoma or other mass.
• Toxic—tick bite paralysis ( Dermacentor  spp. 
(humans), Ixodes holocyclus ).
Bilateral Peripheral
• Immune-mediated—polyradiculoneuritis 
(coonhound paralysis), polyneuropathy, 
myasthenia gravis.
• Metabolic—paraneoplastic polyneuropathy 
(e.g., insulinoma), hypothyroidism.
• Toxic—botulism.
CNS
• Most unilateral.
• Infectious—viral, bacterial, fungal, 
rickettsial, protozoal encephalitis.
• Inflammatory—meningoencephalitis of 
unknown etiology (MUE).
• Neoplastic—primary such as meningioma, 
choroid plexus tumor, lymphoma; metastatic 
tumor such as hemangiosarcoma, carcinoma.
Chronic otitis externa and otitis media.
  DIAGNOSIS
• Differentiate unilateral from bilateral 
• Look for other neurologic deficits—
behavior change, gait disturbance, other CN 
deficits.
• Idiopathic—diagnosis of exclusion; no 
historical or physical signs of ear disease and 
no other neurologic deficits.
• Hypothyroidism—with clinical evidence 
(e.g., lethargy, poor hair coat, weight gain, 
anemia, hypercholesterolemia, ↓FT4, ↑canine 
thyroid-stimulating hormone [cTSH]).
• Otitis media–interna—Horner’s syndrome, 
head tilt, and KCS may be simultaneously 
present.
• CNS disease—if there is somnolence, gait 
disturbances, or other CN deficits.
• Usually normal in idiopathic facial 
paralysis.
• Fasting hypercholesterolemia, normocytic/
normochromic nonregenerative anemia may 
be observed with hypothyroidism-associated 
facial paralysis.
• Hypoglycemia with insulinoma.
• Indicated for patients with suspected 
underlying disease
• Insulin : glucose ratio to detect insulinoma.
• Acetylcholine receptor antibodies to 
diagnose myasthenia gravis.

484  Blackwell’s Five-Minute Veterinary Consult  
F• Free T4 (ideally by equilibrium dialysis) and 
cTSH to diagnose hypothyroidism.
IMAGING
• CT—sensitive to evaluate middle–inner ear 
diseases, preferred modality to evaluate bony 
structures in middle ear.
• MRI—superior to CT for intracranial 
imaging, preferable for CNS disease; contrast 
enhancement of facial nerve in dogs with 
idiopathic facial nerve paralysis; the greater 
the extent of enhancement, the poorer the 
prognosis for return to function.
• Bullae radiographs—four views; two 
obliques, 30° open mouth, dorso-ventral; not 
sensitive for middle–inner ear diseases.
• Schirmer test—evaluate tear production 
(normal >15 mm in 60 seconds), should 
always be performed when evaluating a 
patient with facial paresis/paralysis.
• Fluorescein test—evaluate for presence of 
corneal ulceration secondary to KCS.
• Otoscopic examination—evaluate integrity 
of tympanic membrane and for evidence of 
• Cerebrospinal fluid (CSF)—evaluate for 
evidence of intracranial disease; not sensitive 
if used alone, should be combined with 
diagnostic imaging (e.g., MRI).
• Facial muscle electromyography—evaluate 
for denervation and neuromuscular disease.
• Facial and trigeminal nerve reflex 
electrodiagnostic testing—evaluate peripheral 
nerve integrity, distinguish between 
peripheral and central lesions.
Idiopathic—may see degeneration of large 
and small myelinated fibers without evidence 
of inflammation.
  TREATMENT
• Outpatient—idiopathic facial paralysis.
• Inpatient—initial medical workup and 
management of systemic or CNS disease if 
present.
DIET
No change required.
• Clinical signs may be permanent; however, as 
muscle fibrosis develops, there is a natural “tuck 
up” of the affected side that reduces asymmetry; 
drooling usually stops within 2–4 weeks.
• Inform client that other side can become 
affected.
• Discuss eye care—cornea on affected side 
may need lubrication; extra care may be needed if animal is a breed with natural 
exophthalmia; client must regularly check 
eyes for redness, discharge, or pain that may 
indicate corneal ulcer.
• Inform client that most animals tolerate 
this nerve deficit well; there is no significant 
impact on quality of life.
Bulla osteotomy may be indicated for patients 
with disorders of middle ear.
• T reat specific disease if possible (e.g., 
thyroxine for hypothyroidism).
• Idiopathic disease—no treatment required; 
efficacy of corticosteroids unknown and used 
commonly in humans to treat Bell’s palsy, 
however are not recommended in veterinary 
medicine at this time.
• Tear replacement if Schirmer test value low 
(<15 mm), in patients with KCS or with 
exophthalmic globes.
If middle ear disease is suspected, and 
tympanic membrane may be ruptured, do not 
use topical ear cleaning solutions due to risk 
of ototoxicity.
N/A
  FOLLOW-UP
• Reevaluate early for evidence of corneal 
ulcers.
• Reassess monthly (for 2–3 months) for 
menace responses, palpebral reflexes, and lip 
and ear movements to evaluate return of 
function, condition of affected eye, and 
development of other neurologic deficits that 
would indicate progressive disease.
N/A
• KCS.
• Corneal ulcers.
• Permanent facial asymmetry (aesthetic 
only).
• Depends on underlying cause if one is 
present.
• Idiopathic disease—prognosis guarded for 
full recovery.• Improvement may take weeks or months or 
may never occur.
• Lip contracture sometimes develops.
• Corneal ulcers may perforate and require 
enucleation.
Otitis
N/A
N/A
SYNONYMS
• Facial neuritis.
• Facial palsy.
• Idiopathic facial neuropathy.
SEE ALSO
• Otitis Media and Interna.
• cTSH = canine thyroid-stimulating 
hormone.
• MUE = meningoencephalitis of unknown 
etiology.
Cook LB. Neurologic evaluation of the ear. 
34:425–435.
de Lahunta A, Glass EN, Kent M. Veterinary 
ed. St. Louis, MO: Elsevier Saunders, 2015, 
pp. 172–180.
Jeandel A, Thibaud JL, Blot S. Facial and 
vestibular neuropathy of unknown origin in 
16 dogs. J Small Anim Pract 2016, 
57:74–78.
Kern TJ, Erb HN. Facial neuropathy in dogs 
and cats: 95 cases (1975–1985). J Am Vet 
Med Assoc 1987, 191(12):1604–1609.
Varejao AS, Munoz A, Lorenzo V. Magnetic 
resonance imaging of the intratemporal 
facial nerve in idiopathic facial paralysis in 
the dog. Vet Radiol Ultrasound 2006, 
47(4):328–333.
Author  Andrea M. Finnen
available onlineFacial Nerve Paresis and Paralysis  (continued)

Canine and Feline, Seventh Edition  485
FFalse Pregnancy
  BASICS
• Physical and behavioral changes resulting 
from normal hormonal changes during 
diestrus and early anestrus in the nonpregnant 
bitch. The term false pregnancy is a misnomer, 
since the pattern of hormonal changes is 
normal.
• Physical, hormonal, and behavioral changes 
following a nonfertile mating or spontaneous 
ovulation in the queen.
• Hormone profile of pregnant and nonpregnant 
bitch very similar following ovulation.
• All cycling bitches undergo a lengthy (2+ 
months) diestrus following ovulation.
• Mammary development and behavioral 
changes occur under the influence of 
progesterone and prolactin in late diestrus.
• Galactorrhea (excessive production and 
inappropriate excretion of milk) is seen 
following a rise in serum prolactin at the end 
of diestrus, and also in dogs with severe 
hypothyroidism due to resulting 
hyperprolactinemia.
• False pregnancies in the bitch are thought 
to occur as a holdover from a period in 
evolution when females of a pack would cycle 
at the same time, but only dominant 
individuals would become pregnant. 
Nonpregnant pack members were available to 
nurse puppies of the more dominant females.
• Any event that results in an abrupt drop in 
serum progesterone and rise in prolactin can 
lead to a clinically overt false pregnancy. Signs 
are frequently created iatrogenically when 
ovariectomy (OVE) or ovariohysterectomy 
(OHE) is performed during mid to late diestrus.
• Queens that ovulate spontaneously or ovulate 
following mating but do not become pregnant 
experience a 6–7-week period of diestrus due to 
elevated progesterone concentrations; some 
queens develop a clinically overt false pregnancy 
during this time.
• Endocrine.
GENETICS
N/A
• False pregnancies occur in 100% of bitches 
following ovulation.
• >60% of cycling bitches exhibit signs of 
false pregnancy.
• Spontaneous ovulation occurs frequently in 
the queen (35–85%) depending on presence of 
other queens and tom. False pregnancy occurs 
after every nonpregnant ovulation in the 
queen, but overt symptoms are uncommon.SIGNALMENT
Species
None
Any age.
Female only.
SIGNS
• Although all cycling bitches have similar 
progesterone and prolactin hormone profiles 
during late diestrus and early anestrus, they vary 
in the magnitude of clinical symptoms associated 
with the false pregnancy. This may be due in part 
to individual sensitivities to prolactin.
• Some bitches experience repeated overt false 
pregnancies, while others have covert false 
pregnancies.
• The magnitude of symptoms can vary 
during individual false pregnancies for the 
same bitch.
• Overt symptoms are uncommon in queens.
• Estrus—bitch: ~6–12 weeks previously; 
queen: ~40 days previously.
• OVE or OHE during diestrus, 3–14 days 
prior to presentation.
• Mammary gland development.
• Galactorrhea.
• Behavior change including nesting, 
maternal behavior, aggression, lethargy.
• Inappetence.
• Abdominal distension (rare).
• Mammary gland hypertrophy.
• Galactorrhea—fluid can be clear to milky 
to brown in color.
CAUSES
• Decline in serum progesterone 
concentration and rise in serum prolactin 
concentrations due to OVE or OHE during 
diestrus.
• Hyperprolactinemia—can be due to severe 
• OHE or OVE during diestrus.
• Does not impact future fertility.
  DIAGNOSIS
• Mastitis.• Mammary neoplasia.
• Mammary hyperplasia (queens).
• Other causes of abdominal distension 
(organomegaly, ascites).
• Pituitary tumor causing hyperprolactinemia 
(rare).
• Normocytic, normochromic anemia—17–21% 
decrease in hematocrit during late diestrus.
• Hypercholesterolemia—75–94% increase 
during diestrus.
Serum progesterone concentrations elevated if 
tested during diestrus.
IMAGING
• Ultrasonography—uterine enlargement; 
performed after 25 days from mating; can be 
used to evaluate for pregnancy and uterine 
fluid accumulation.
• Radiography—normal; performed after 54 
days from mating; can be used to detect presence 
of fetal skeletons and uterine fluid accumulation.
N/A
N/A
  TREATMENT
• Usually no treatment needed.
• Outpatient treatment for medical 
management of severe clinical signs of false 
pregnancy.
• Prevent mammary gland stimulation from 
self-nursing with Elizabethan collar or body suit.
• Owners can cold pack mammary glands to 
reduce mammary gland activity.
ACTIVITY
Increase activity in sedentary dogs and cats to 
increase caloric expenditure and decrease 
calories available for lactation.
DIET
Decrease caloric intake for several days to 
reduce energy available for lactation.
• False pregnancies are normal in bitches and 
do not impact future fertility.
• Advise cat owners that pyometra can 
develop following spontaneous ovulations.
• OVE or OHE if bitch or queen is not 
intended for use in a breeding program.
• Perform OVE or OHE during anestrus or 
early diestrus when possible.

486  Blackwell’s Five-Minute Veterinary Consult  
F  MEDICATIONS
• Dopamine agonists—reduce milk 
production and some maternal behaviors by 
inhibiting prolactin release.
• Cabergoline 5  μg/kg PO q24h for 5–7 
days.
• Bromocriptine 10  μg/kg PO q8h for 5–7 
days.
Dopamine agonists can cause abortion if 
given to a pregnant bitch or queen, as 
prolactin is luteotrophic. Drugs that suppress 
prolactin will terminate pregnancy by 
reducing progesterone and can cause 
premature parturition (abortion).
• Incidence of vomiting with bromocriptine 
administration reduced if given with food; 
cabergoline has fewer side effects and higher 
efficacy, but is more costly.
• Coat color changes in dogs possible with 
prolonged dopamine agonist treatment 
(uncommon).
Avoid acepromazine and metoclopramide; 
both can promote lactation and reduce 
efficacy of dopamine agonists.
• Short-term therapy with diazepam can be 
useful for bitches with extreme behavioral 
signs.
• Mibolerone 16  μg/kg PO q24h for 5–7 days 
to reduce symptoms of false pregnancy. Can 
also be used at 2.6  μg/kg/day PO starting at 
least 1 month prior to the next heat cycle to 
suppress estrus in bitches, which will prevent 
recurrence. Side effect and risks of treatment should be explained and owners should give 
informed consent prior to treatment. Do not 
give to cats.
  FOLLOW-UP
Have owners monitor mammary glands for 
inflammation and discoloration that could 
indicate mastitis.
• Estrus suppression.
Mastitis with significant mammary gland 
hypertrophy, galactostasis, and ascending 
• Typically resolves in 4–6 weeks without 
• Resolution in 10–14 days with dopamine 
agonist or mibolerone.
• May recur after any ovulation.
N/A
N/A
N/A
• The tendency to display overt false 
pregnancies has no impact on fertility.• Bitches and queens should be evaluated for 
possible pregnancy before treating for false 
SYNONYMS
• Pseudocyesis.
• Pseudogestation.
• Phantom pregnancy.
• False whelping.
• OVE = ovariectomy.
Gobello C, De La Sota RL, Goya RG. A 
review of canine pseudocyesis. Reprod Dom 
Anim. 2001, 36:283–288.
Kowalewski MP . Endocrine and molecular 
control of luteal and placental function in 
dogs: a review. Reprod Domest Anim 2012, 
47(Suppl 6):19–24.
Lee WM, Kooistra HS, Mol JA, et al. 
Ovariectomy during the luteal phase 
influences secretion of prolactin, growth 
hormone, and insulin-like growth factor-I 
in the bitch. Theriogenology 2006, 
66(2):484–490.
Root AL, Parkin TD, Hutchison P , et al. 
Canine pseudopregnancy: an evaluation of 
prevalence and current treatment protocols 
in the UK. BMC Vet Res 2018, 14(1):170.
Verstegen-Onclin K, Verstegen J. 
Endocrinology of pregnancy in the dog: a 
review. Theriogenology 2008, 
70:291–299.
Author  Milan Hess
available onlineFalse Pregnancy  (continued)

Canine and Feline, Seventh Edition  487
FFamilial Shar-Pei Fever
  BASICS
A hereditary autoinflammatory disease in the 
Chinese Shar-Pei dog characterized by 
episodic fever and progressive systemic 
amyloidosis.
• Multifactorial disorder caused by genetic 
defects that induce chronic inflammation and 
reactive amyloidosis. Environmental factors 
and gene modifiers play a role.
• Associated with the thick skin phenotype, 
resulting from an excessive dermal deposition 
of hyaluronic acid (HA) by increased 
expression of hyaluronic acid synthase 2 
(HAS2).
• Overabundant HA is degraded into low 
molecular weight HA, triggering release of 
inflammatory interleukins.
• Elevated inflammatory cytokines increase 
serum amyloid A (SAA) concentration. SAA 
is deposited extracellularly throughout the 
tissues.
• Amyloid deposition may cause organ 
failure, particularly in kidneys and liver.
• Musculoskeletal—nonerosive 
polyarthropathy, frequently affecting the 
tibiotarsal joints.
• Skin—periarticular edema, especially 
around the tibiotarsal region, swollen muzzle, 
icterus, skin sloughing.
• Renal/urologic—amyloid deposition in 
renal medulla, glomerular amyloidosis, renal 
failure, proteinuria.
• Hepatobiliary—impaired hepatic function; 
hepatomegaly; friable liver, hepatic rupture 
and hemoabdomen (rare).
• Hemic/lymphatic/immune—inflammatory 
response; anemia; coagulation defects; 
hypercoagulability; hyperglobulinemia; 
occasionally decreased immunoglobulin (Ig) 
A or IgG levels.
• Gastrointestinal (GI)—submucosal amyloid 
deposition; GI ulceration due to renal or 
hepatic failure.
• Cardiovascular—venous thrombosis; 
systemic hypertension.
• Nervous—vascular accident; hepatic 
• Ophthalmic—retinal detachment.
• Respiratory—pleural effusion; pulmonary 
GENETICS
• Autosomal recessive inherited disorder. 
Different modes of inheritance proposed.
• A greater number of mutations in the 
“meatmouth” (or heavily wrinkled) shar-pei 
phenotype increases risk.INCIDENCE/PREVALENCE
• Estimated 23–28% of shar-pei dogs.
• Estimated 53% of shar-pei dogs with fever.
• Mean age—4 years.
• Range—19 weeks–9 years.
• Sex predisposition—female (female : male, 
2.5 : 1).
SIGNS
Findings vary depending on distribution and 
severity of amyloidosis.
• Episodic anorexia, lethargy, stiffness, 
swollen hocks and/or muzzle—self-limiting 
(12–36 hours) or responsive to nonsteroidal 
• Intermittent abdominal pain, vomiting, 
and/or diarrhea.
• Polyuria and polydipsia.
• Marked fever 39.4–41.7 °C (103–107 °F) 
of 12–36-hour duration.
• Lethargy and dehydration.
• Edematous periarticular soft tissue 
• Joint effusion.
• Swollen muzzle.
• Reluctance to move/hunched posture.
• Hepatomegaly, ascites, and icterus.
• Pale mucous membranes secondary to 
chronic anemia or rarely hemoperitoneum.
CAUSES
Dysregulation of inflammatory processes in 
the shar-pei dog induces reactive amyloidosis.
Stress may trigger a fever episode.
  DIAGNOSIS
• Infectious or immune-mediated causes of 
polyarthritis (see Polyarthritis, Nonerosive, 
Immune-Mediated, Dogs).
fever (see Fever).
• Neutrophilia with or without left shift.
• Acute kidney injury (e.g., azotemia, 
hyperphosphatemia, metabolic acidosis, 
isosthenuria).
• Hypoalbuminemia—secondary to 
proteinuria or liver failure.
• Hypercholesterolemia—consistent with 
nephrotic syndrome.• Elevations in serum alkaline phosphatase 
(ALP) and alanine aminotransferase (ALT) 
activities and bilirubin concentration.
• Proteinuria—in cases of glomerular 
• Bilirubinuria—secondary to cholestasis or 
• Genetic tests are available for HAS2 and 
MDM2 binding protein (MTBP) defects.
• Coombs’ test, antinuclear antibody test, 
and rheumatoid factor identify concurrent 
underlying immune-mediated disease.
• Prothrombin time (PT) and partial 
thromboplastin time (PTT)—can be 
prolonged with liver failure and disseminated 
intravascular coagulation (DIC); DIC may 
result in increased D-dimer concentration.
• Antithrombin activity—may be low 
(urinary loss).
• Thromboelastography/elastometry— 
hypercoagulability.
• IgA or IgG levels—may be low.
• Urine protein : creatinine ratio (UPC)—
severely elevated with glomerular deposition 
of amyloid.
IMAGING
• Abdominal radiography—hepatomegaly 
or decreased detail due to peritoneal 
effusion.
• Thoracic radiography—pleural effusion.
• Joint radiography—periarticular swelling of 
the soft tissues without bony involvement.
• Abdominal ultrasonography—diffusely 
hypoechoic liver with rounded edges; kidneys 
may appear hyperechoic with loss of 
corticomedullary distinction.
• Synovial fluid analysis—may reveal acute 
synovitis.
• Kidney and/or liver fine-needle aspiration 
or biopsy (pending coagulation testing, 
biopsy preferred)—amyloid deposition, 
confirmed by Congo red staining and 
polarized light.
Deposition of amyloid in multiple organs, 
associated primarily with vessels or within the 
  TREATMENT
• Minor episodes of pain and fever—
outpatient care.
• Inpatient care required for severe fever, 
anorexia, dehydration, lameness or 
nonspecific pain, vomiting and/or diarrhea.
• Intensive care may be required to treat organ 
failure or sequelae of thromboembolism.

488  Blackwell’s Five-Minute Veterinary Consult  
FNURSING CARE
• IV isotonic crystalloid fluids—for 
dehydration, anorexia, vomiting and/or 
diarrhea.
• Oxygen—to treat hypoxemia.
• Abdominocentesis/thoracocentesis—if 
effusion causes respiratory compromise or 
elevated intra-abdominal pressure.
• Blood transfusions—to treat anemia.
• Fresh frozen plasma—consider for 
coagulopathies, DIC.
DIET
• Protein and phosphorus restriction in 
accordance with IRIS renal staging.
• Dogs with hepatic encephalopathy should 
be fed protein-restricted diet.
• Omega-3 fatty acids may be beneficial for 
glomerular disease.
• There is no cure; therapy is palliative and 
lifelong.
• Early therapy may decrease further 
deposition of amyloid.
• Diagnostics should be performed to 
ensure there is no underlying or concurrent 
disorder.
• Affected dogs should not be bred; genetic 
testing available.
• Colchicine 0.03 mg/kg PO q24h; advised 
early in course of disease to delay amyloid 
deposition; unknown if beneficial once 
amyloid has been deposited.
• Corticosteroids—if concurrent  
immune-mediated disease is present.
• Clopidogrel (1–2 mg/kg PO q24h) if 
concerned about hypercoagulability.
inhibitor (e.g., enalapril or benazepril 
0.25–0.5 mg/kg PO q12–24h) or 
angiotensin receptor blocker (ARB; e.g., 
telmisartan 1 mg/kg PO q24h) for 
proteinuria (may cause transient 
worsening of azotemia).
• Anti-hypertensive therapy if indicated.
• Antibiotics—for concurrent infection or 
sepsis.
• NSAIDs/analgesics for fever and pain, 
unless corticosteroids have been given.
• Gastroprotectants—if gastric ulcer 
suspected.CONTRAINDICATIONS
• NSAIDs contraindicated in patients with 
renal disease, GI upset, and in combination 
with corticosteroid therapy.
• ACE inhibitors/ARBs contraindicated in 
dehydrated or hypovolemic patients.
Colchicine can cause GI upset; chronic use 
can be associated with bone marrow 
Concurrent use of colchicine and cyclo-
sporine increases risk of colchicine toxicity.
  FOLLOW-UP
• Blood pressure measurement and fundic 
examination—monitor for hypertension.
• Urinalysis and UPC.
• Biochemistry panel—renal and hepatic 
parameters, including albumin.
• CBC—to assess anemia and inflammation.
Avoid puppies from lines that have a history 
of shar-pei fever.
• Death—due to hepatic rupture or 
pulmonary thromboembolism (PTE).
• Neutrophilic vasculitis causing severe skin 
sloughing; streptococcal toxic shock 
syndrome causing localized necrotizing 
fasciitis and/or concurrent shock and 
multiorgan failure.
• Waxing and waning, progressive disorder 
with a fair to poor prognosis, depending on 
timing of diagnosis.
• Inevitably fatal due to chronic kidney 
disease or hepatic failure.
• Time course may be weeks to more than 
10 years.
Most severe in cases diagnosed at an early age.
Do not breed affected dogs.SYNONYMS
• Swollen hock syndrome.
• Shar-pei autoinflammatory disorder.
SEE ALSO
• Icterus.
• HA = hyaluronic acid.
• HAS2 =hyaluronic acid synthase 2.
• MTBP = MDM2 binding protein.
drug.
• SAA = serum amyloid A.
• UPC = urine protein : creatinine ratio.
• www.drjwv.com
• www.iris-kidney.com
• www.wvc.vetsuite.com
DiBartola SP , Tarr MJ, Webb DM, et al. 
Familial renal amyloidosis in Chinese Shar 
Pei dogs. J Am Vet Med Assoc 1990, 
197:483–487.
May C, Hammill J, Bennett D. Chinese shar 
pei fever: A preliminary report. Vet Rec 
1992, 26:586–587.
Metzger J, Nolte A, Uhde AK, et al. Whole 
genome sequencing identifies missense 
mutation in MTBP in Shar-Pei affected 
with Autoinflammatory Disease (SPAID). 
BMC Genomics 2017, 18(1):348.
Olsson M, Tintle L, Kierczak M, et al. 
Thorough investigation of a canine 
autoinflammatory disease (AID) confirms 
one main risk locus and suggests a modifier 
locus for amyloidosis. PLoS One 2013, 
8(10):e75242.
Author  Bianca N. Lourenço
Julie Armstrong.Familial Shar-Pei Fever  (continued)

Canine and Feline, Seventh Edition  489
FFanconi Syndrome
  BASICS
OVERVIEW
Defective proximal renal tubular reabsorption 
of glucose, electrolytes, and amino acids.
Species
Dogs and rarely cats.
Sporadically reported in several breeds, 
idiopathic Fanconi syndrome primarily affects 
the basenji breed (approximately 75% of 
cases). In America, 10–30% of basenjis are 
affected. It is presumed to be inherited in this 
breed, but the mode of inheritance is 
unknown.
Age at diagnosis: 10 weeks–11 years. Affected 
basenjis usually are >2 years of age; most 
develop clinical signs from 4 to 7 years.
None
SIGNS
• Depends on the severity of specific solute 
losses and residual renal function.
• Loss of amino acids and glucose—usually 
not associated with clinical signs other than 
polyuria and polydipsia.
• Uremia, lethargy, decreased appetite.
• Abnormal growth (rickets) may occur in 
young animals.
• Inherited in basenjis and possibly Irish 
wolfhounds.
• Acquired Fanconi syndrome has been 
reported in dogs given gentamicin, 
streptozotocin, maleic acid, amoxicillin, 
chlorambucil (cats), and chicken or duck 
jerky treats, many of which have originated 
from China; also reported secondary to 
primary hypoparathyroidism, copper 
associated hepatopathy, and lead toxicity.
  DIAGNOSIS
Primary renal glucosuria causes glucosuria 
despite normoglycemia; documentation of 
aminoaciduria, mild proteinuria, or a 
hyperchloremic normal anion gap metabolic 
acidosis suggests Fanconi syndrome.
• CBC usually normal.
• Hyperchloremic metabolic acidosis.• Azotemia if renal failure develops.
• Hypophosphatemia and hypocalcemia may 
occur in affected young, growing animals.
• Urine specific gravity usually low (1.005–
1.018); mild proteinuria common; ketonuria 
may be present.
• Granular or lipid casts and bacteria were 
seen in 27–40% of dogs.
Hyperchloremic normal anion gap metabolic 
acidosis due to bicarbonaturia with urine pH 
<5.5. Urine pH >6.0 in distal renal tubular 
acidosis, which is key diagnostic difference to 
proximal renal tubular acidosis (Fanconi 
IMAGING
Radiography—young growing dogs may have 
rickets and angular limb deformities; adults 
may have decreased bone density.
Urinary clearance studies to document 
excessive excretion of glucose, amino acids, 
and electrolytes needed for confirmation. Do 
not test animals <8 weeks of age because 
false-positive results may occur. Urine can be 
evaluated at PennGen for aminoaciduria. 
Fractional reabsorption of amino acids in 
affected dogs ranges from 50% to 96% 
(normal 97–100%).
Renal papillary necrosis may occur in late disease.
  TREATMENT
• Discontinue any drug or treats that may 
cause Fanconi syndrome or treat for specific 
• No treatment reverses transport defects in 
dogs with inherited or idiopathic disease.
• Because magnitude of transport defects 
varies among affected animals, treatment 
must be individualized.
• T reat for metabolic acidosis if blood 
bicarbonate concentration <12 mEq/L. Large 
doses of alkalinizing agents may be required 
because decreased proximal tubular resorptive 
capacity results in marked bicarbonaturia. 
Goal of alkali therapy to maintain blood 
bicarbonate concentration 12–18 mEq/L.
• Young, growing dogs may require vitamin D, 
calcium, and phosphorus supplementation.
Use potassium citrate or sodium bicarbonate 
(start with low dosage) as dictated by blood 
gas and electrolyte data.CONTRAINDICATIONS/POSSIBLE 
• Avoid drugs that are nephrotoxic or have 
potential to cause Fanconi syndrome (see 
Causes & Risk Factors).
• Avoid potassium chloride if hyperchloremic.
  FOLLOW-UP
• Monitor serum biochemistry at 14-day 
intervals to assess treatment response; 
monitor serum potassium concentration 
regularly as bicarbonate therapy may 
aggravate renal potassium loss; once stable, 
monitor biochemistry at 3-month intervals.
• Clinical course varies; some dogs remain 
stable for years, others develop rapidly 
progressive renal failure over a few months; 
cause of death usually acute kidney injury 
with severe metabolic acidosis.
• Some dogs (18% in one study) developed 
seizures or other neurologic signs several years 
after diagnosis.
SEE ALSO
• https://www.vet.upenn.edu/research/
penngen
• http://www.basenji.org/ClubDocs/
fanconiprotocol2003.pdf
Thompson M, Fleeman L, et al. Acquired 
proximal renal tubulopathy in dogs exposed 
to a common dried chicken treat: 
retrospective study of 108 cases (2007–2009). 
Aust Vet J 2013, 91(9):368–373.
Authors  Joao Felipe de Brito Galvao and 

F
490  Blackwell’s Five-Minute Veterinary Consult  
FFear and Aggression in Veterinary Visits—Cats
  BASICS
• Fear—involuntary, negative emotional 
state caused by anticipation/awareness of 
danger. • Aggression —warning/intent to 
cause harm/increase distance to perceived 
threat.
See Causes and Risk Factors.
• Behavioral —neurochemical input between 
limbic system and forebrain. • Sympathetic 
nervous system arousal.
GENETICS
Fearful/fractious temperaments are heritable.
Up to 85% of cats stressed at physical exam.
None
Species
Cat
Any
Any
Any
SIGNS
Fearful body language—dilated pupils, ears 
back, crouching, hissing, growling, tail 
thrashing, swatting.
CAUSES
• Previous frightening/painful experience. 
• Fearful temperament.
History of fearful/fractious behavior to 
handling, unfamiliar people, travel, or at 
previous visits.
  DIAGNOSIS
• Pain. • Irritability from illness. • Forebrain 
lesion. • Cognitive dysfunction syndrome.
Stress leukogram; hyperglycemia; glucosuria.
IMAGING
If indicated to rule out medical conditions, 
e.g., pain.
If indicated to rule out medical conditions.
Stress related increase in blood pressure, heart 
rate, temperature, respiratory rate.  TREATMENT
Prior to Handling
Assess environment, patient, and veterinary 
personnel. What cats see, smell, feel, taste, 
and hear affects emotional state and can lower 
aggression threshold.
Assess Environment: Make Cat 
Comfortable
• Reduce carrier/transport stress. • Eliminate/
avoid triggers. • Modify environmental stimuli—
light, noises, sound level (stress at ≥80 DB), 
movement, touch, temperature (30–36 °C). 
• Comfortable exam site (no slippery, shiny, cold 
surfaces). • Allow cats to hide, feel secure.
Assess Animal: Anxiety/Fear/Arousal 
Fuel Aggression
• Body language interpretation is critical. 
• T rack willingness to approach, interact with 
environment and people. • Intervene early. 
• Change in location (examination vs. 
treatment area), interaction, procedure, 
personnel can affect patient.
Assess Yourself: Avoid Perceived 
Threats, Track Body Postures 
and Behavior
• Avoid direct eye contact or putting face near 
fearful cat. • Avoid petting top of head, 
grabbing body, or reaching into carrier. 
• Remove carrier tops —do not pull or dump 
cat. • Allow time to sniff your hand; gently 
scratch under chin and side of head if postures 
indicate safety; avoid petting beyond shoulder—
often overarousing. • Start exam at head or 
middle and move back; save socially invasive 
(head, feet, rear, belly) or painful areas for last. 
• Talk softly; work quietly; avoid sudden 
movements. • Often narrow window of 
opportunity before fear/arousal escalates. • Not 
approaching indicates use of social distance to 
cope; anticipate approach may lead to aggressive 
response—make a plan. • Fear or frustration by 
handler increases cat fear. • Use language that is 
scientifically accurate and promotes patient 
empathy—fearful, painful, confused; avoid 
labels that result in poor handling and offend 
clients—evil, spiteful, mean, bad, stupid. 
• Strictly avoid punishment (verbal or physical).
Make Handling Plan
• Handling plans unique to individual cats, 
environment, and procedures and require 
adjustments based on patient response. • Make 
plan for safety, decreased handling time, 
patient welfare, client satisfaction. • Maintain 
record of likes and dislikes to plan future visits.
Patient Handling Plan Guidelines
• Determine cat’s preferred food/treat for 
distraction and counter-conditioning (CC). 
• Select restraint for individual cat/procedures. 
• Select handling tools that increase safety and 
decrease patient fear/arousal. • Critically 
consider procedures—must it be done today? Consider rescheduling to add oral sedative/
anxiolytics and/or divide treatment into shorter 
visits with fewer procedures. • Place required 
procedures in order of most important to least 
in case not all are tolerated. • Place procedures 
in order of least to most aversive so early 
procedures do not inhibit completion of later 
ones. • Consider pain, invasiveness, number of 
procedures, how patient is coping. • Use 
chemical restraint immediately, prior to any 
necessary procedures in which fear may escalate 
above mild. • Have chemical restraint prepared 
for at-risk patients—use before arousal to 
promote efficacy, safety, reduce future fear.
CC
• Learning where cat’s negative emotional 
response (fear) to stimulus (veterinary setting) is 
changed to positive one (pleasure). • Food is 
easiest/most powerful way to create this shift. 
• Palatability must be high (e.g., meat baby food, 
squeeze cheese, canned food) to maximize cat’s 
interest/increase positive emotional response. 
• Offer food while cat relaxed/feels safe, then just 
before/during/after any (aversive) procedure. 
• Stressed cats may need food for duration of 
handling to prevent escalation of fear/arousal. 
• Barometer—stressed cats often reject food.
Guidelines for Restraint
• Create safe handling plan for each procedure; 
use least restraint required. • Avoid over-
restraint—causes more stress than procedure 
itself. • If greater restraint needed, use balanced 
pressure with global support. • Prevent 
flailing—control head/rear. • Avoid scruffing—
use only for cats comfortable with technique. 
• Avoid stretching—use lateral recumbency only 
if procedure requires. • Avoid multiple bouts of 
restraint; adjust position by sliding hands along 
body instead of release/regrab. • Struggling 2 
seconds—stop, reposition, try again; wait for cat 
to relax to resume. • Second attempt—if not 
relaxed and/or starts to get fractious, stop; is 
procedure essential? • If essential—use chemical 
restraint. • If nonessential—send home with 
handling plan and medication if indicated for 
return visit. • Owner presence—can provide 
secure base and reduce stress.
Handling Tools
Expedite procedures by reducing patient fear, 
minimizing manual restraint, and increasing safety.
Pheromones: F3 Cheek Gland (Feliway® 
Classic)
• Diffusers—reception, exam rooms, wards. 
• Spray/wipes—travel, examination, cages.
Muzzles
Toweling preferred.
Towels
• Towel/thick bedding for immobilization—
protects cat from flailing, handler from bites/
scratches. • Provides head/body control, avoids 
visual stimuli, firm global pressure—can modify 
to gain head/jugular or front/back leg access. 
• Allows auscultation, abdominal palpation. 
• Safe restraint of fleeing/fearful cats, removal 
from carrier/cage, chemical restraint injection.

Canine and Feline, Seventh Edition  491
FFMusic
Classical music and cat-specific music may mask 
stressful external sounds, relax patients, have 
potential calming effects on clients and staff.
Cat Carrier
• Positively condition/train cats to carrier prior to 
travel. • Select carrier that allows cat to easily exit 
or remain in lower portion for exam (removable 
top). • Provides familiar area, prevents fleeing, 
promotes hiding. • Soft-sided/mesh panels—can 
press mesh against cat’s body for safe IM injection. 
• Place carrier in cage of hospitalized cat—offers 
familiarity, encourages faster return to eating.
Restraint Nets (EZ Nabber)
• Provides safe option for catch/restraint for 
prompt administration of IM injections. 
• Very effective for cats housed in wall unit 
cages. • Cover with towel once cat inside—
reduces visual stimulation, protects handler.
N/A
ACTIVITY
N/A
DIET
N/A
• Preventive counseling (start at first visit)—
positive carrier training, travel, handling, 
feline communication, reward training, avoid 
use of punishment. • Provide kitten classes in 
veterinary clinic. See Internet Resources.
N/A
Chemical Restraint
• Allows safe handling, effective completion of 
procedures. • Blocks/prevents fear, discomfort, 
pain, further distress, and fear escalation. 
• Minimal or no physical restraint. 
• Injectable sedation (IM) most effective for 
safe handling of fractious/highly fearful 
patients. • Base protocol on age, temperament, 
health. • Pre-travel oral anxiolytics/sedatives 
reduce fear, facilitate gentle handling, promote 
safety for injection, reduce injectable doses.
Oral Sedative/Anxiolytics
• Administer 60–90 min prior to travel for mild/
moderate fear, or to facilitate administering 
chemical restraint. • May give first dose 12h in 
advance. • Also may be required for inpatients. 
• Gabapentin—10–20 mg/kg PO (50–150 mg/
cat). • T razodone—25–50 mg/cat PO. 
• Lorazepam—0.05–0.25 mg/kg PO (0.125–
0.25 mg/cat). • Buprenorphine—  
0.01–0.03 mg/kg oral transmucosal (OTM). 
• For additional sedation can add 
acepromazine—0.5–2.2 mg/kg PO.
Injectable Sedation/Chemical Restraint
• Young/healthy— dexmedetomidine 10–20  μg/
kg or acepromazine 0.1 mg/kg + opioid; for additional sedation can add ketamine 3–5 mg/kg 
IM. • Alternative —tiletamine/zolazepam 
5–10 mg/kg IM. • Geriatric/ill— acepromazine 
0.01–0.05 mg/kg or dexmedetomidine 5–10  μg/
kg + opioid: for greater sedation add ketamine 
3–5 mg/kg IM; hydromorphone 0.05 mg/kg + 
midazolam 0.1–0.2 mg/kg ± ketamine 3–5 mg/
kg ± acepromazine 0.01–0.05 mg/kg; alfaxalone 
1–2 mg/kg + midazolam 0.2 mg/kg ± opioid ± 
acepromazine 0.01–0.05 mg/kg. • Can reverse 
dexmedetomidine—½ volume atipamezole to 
volume of dexmedetomidine administered IM. 
• Dexmedetomidine/ketamine protocols—to 
avoid dysphoria wait 45–60 min to reverse. 
• Opioid choices (full Mu agonist superior for 
pain control)—butorphanol 0.2 mg/kg; 
buprenorphine 0.01–0.03 mg/kg; morphine 
0.2 mg/kg; hydromorphone 0.05–0.1 mg/kg; 
oxymorphone 0.1 mg/kg.
Reports of acute hepatic necrosis with oral 
diazepam.
• Have client perform drug trial at home to 
determine response/ideal dose. • Agitation, 
gastrointestinal upset, sedation, appetite 
changes possible with above oral medications. 
• Benzodiazepines—disinhibition of aggression 
uncommon but possible. • Gabapentin—
caution with chronic renal disease.
N/A
Natural products including pheromones and 
supplements containing l-theanine or 
alpha-casozepine.
  FOLLOW-UP
• Evaluate physiologic/behavioral parameters. 
• Evaluate and record response to handling, 
location, personnel, products, drugs.
• Prevention—more effective, safer, less expense, 
improves healthcare compliance, avoids fear 
sensitization. • Low Stress handling and CC 
during all kitten and adult visits recommended.
Fearful and/or aggressive behavior negatively 
impacts frequency and level of veterinary care.
Effective implementation of Fear Free, Low 
Stress, and Cat Friendly visits reduces fear, 
anxiety, and stress and improves frequency 
and quality of veterinary care.
Fearful/fractious cats in veterinary setting often 
have comorbid behavioral problems at home, such as aggression to owners or strangers, 
undesirable elimination, and anxiety disorders.
• Socialization period (2–7 weeks)—time 
where positive early exposure minimizes fear. 
• Regular, gentle, brief exposure to handling 
paired with positive experience (food) leads to 
less fear/improved future handling.
Bite wounds and associated infections.
Fearful/aggressive temperaments are heritable.
SYNONYMS
• Fear aggression. • Defensive aggression. 
• Phobic behavior.
SEE ALSO
• Car Ride Anxiety—Dogs and Cats.
• Kitten Socialization and Kitten Classes.
• OTM = oral transmucosal.
Travel
• https://catfriendly.com/be-a-cat-friendly-
caregiver/getting-cat-veterinarian • www.
catalystcouncil.org/resources/health_welfare/
cat_carrier_video/index.aspx
Veterinary Visits
• https://https://fearfreehappyhomes.com/
courses/how-to-prepare-your-pet-for-vet-visit/ 
• https://fearfreehappyhomes.com/courses/
how-to-make-trip-to-vet-fear-free/
Body Language
• https://www.dacvb.org/page/cats • https://
fearfreehappyhomes.com/courses/
cat-body-language-101
General
• http://www.fearfreepets.com • http://www.
catalystcouncil.org • https://www.
partnersforhealthypets.org/practice_feline.
aspx • https://lowstresshandling.com 
• https://www.catvets.com/guidelines/
practice-guidelines/handling-guidelines 
• https://www.aaha.org/aaha-guidelines/
behavior-management/behavior-
management-home/ • http://www.
cat_friendly_practices • https://icatcare.org/
advice/cat-handling-videos
Herron M, Shreyer T. The pet friendly 
veterinary practice: a guide for practitioners. 
44:451–481.
Yin S. Low Stress Handling, Restraint, and 
Behavior Modification of Dogs and Cats. 
Davis, CA: Cattle Dog Publishing, 2009.
Authors  Meghan E. Herron and T raci A. Shreyer
Consulting Editor  Gary M. Landsberg(continued)  Fear and Aggression in Veterinary Visits—Cats

F492  Blackwell’s Five-Minute Veterinary Consult  
FFear and Aggression in Veterinary Visits—Dogs
  BASICS
• Fear—involuntary, negative emotional state 
caused by anticipation/awareness of danger. 
• Aggression—warning/intent to cause harm/
increase distance in response to perceived threat.
• Behavioral—neurochemical input between 
limbic system and forebrain. • Activation of 
hypothalamic pituitary axis (HPA) and 
sympathetic nervous system.
GENETICS
Fearful temperament may be heritable.
Over 75% fearful when examined.
Species
Dog
Any
Any
Any
SIGNS
Fearful body language—ears back, gaze 
avoidance, crouching, tail tucked, yawning, 
panting, lip licking, scanning.
CAUSES
• Previous frightening/painful experiences. 
• Fearful temperament (genetics, peri/
postnatal experience, socialization).
History of fearful behavior to handling, 
unfamiliar people, noises, environments, or 
  DIAGNOSIS
• Pain. • Irritability from illness. 
• Forebrain lesion. • Cognitive dysfunction 
syndrome.
Stress leukogram; glucosuria.
Stress-induced increase in blood pressure, 
heart rate, temperature, panting.  TREATMENT
Assess environment, dog, and veterinary 
personnel. What dogs see, smell, feel, taste, 
and hear affects emotional state and lowers 
Assess Environment: Make Dog 
• Eliminate known triggers. • Modify 
environmental stimuli including light, noises, 
sound level (stress at ≥80 DB), movement, touch, 
temperature (15–30 °C). • Owner presence—
can provide secure base, reduce stress. 
surfaces). • Allow fearful dogs to hide, feel secure.
Assess Dog
• Anxiety/fear/arousal leading to aggression. 
• Body language interpretation critical. 
environment/people. • Intervene early. 
personnel can affect patients.
• Avoid direct eye contact, bending over, putting 
face near fearful dog, loud talking, sudden 
movements. • Bend at knee, turn to side, squat 
(when safe). • Avoid reaching out, petting top of 
head, grabbing collar. • Encourage patients to 
approach or have handler they trust move them 
to you. ◦ Hand at your side, pat your leg gently, 
soft verbal encouragement. ◦ Palm open with 
valued treats. ◦ Allow dog to sniff/investigate. 
◦ Gently pet under chin/neck. ◦ Test 
acceptance—stop petting, does dog reengage. 
◦ If no: stop, make a plan. ◦ If yes: pet again, 
slowly move to desired exam position. ◦ Start 
exam in middle, slowly work to rear, back to 
center, to head. ◦ Monitor/be prepared for any 
fear- or pain-evoking handling. • Not 
cope; approach may lead to aggressive 
response—make a plan. • Avoid front-facing 
interactions or cover dog’s head; work at side, 
just behind point of shoulder, facing same 
direction as dog. • Often narrow window of 
opportunity before fear/arousal escalates. • Fear 
or frustration by handler or veterinary personnel 
increases pet fear; use scientifically accurate 
language that promotes patient empathy—
fearful, painful, confused; avoid labels that result 
in poor handling/offend clients—mean, bad, 
spiteful, dominant. • Strictly avoid punishment 
(verbal or physical).
• Handling plans unique to individual dogs, 
environment, and procedure and require 
adjustments based on dog’s response. • Make plan for safety, decreased handling time, patient 
welfare, and client satisfaction. • Maintain 
record of likes and dislikes to plan further visits.
• Determine most motivating food/treats for 
• Select restraint for individual dog/procedures. 
consider procedures—must it be done today? 
Consider rescheduling to add oral sedative/
in order of least to most aversive, so early 
procedures, how dog is coping. • Use chemical 
restraint immediately for any necessary 
procedures in which fear escalates beyond mild; 
use before arousal to promote efficacy, safety, 
escalation, learning.
CC
• Learning where dog’s negative emotional 
response (fear) to stimulus (veterinary setting) 
is changed to positive one (pleasure). • Food 
easiest/most powerful way to create shift. 
• Palatability must be high (meat baby food, 
squeeze cheese, canned food) to maximize 
dog’s interest/increase positive emotional 
response. • Offer food while dog relaxed/feels 
safe, then just before/during/after any 
(aversive) procedure. • Stressed dogs may 
need food for duration of handling to distract 
and prevent escalation of fear/arousal. 
• Barometer—stressed dogs often reject food.
Restraint
• Create safe handling plan for each procedure. 
• Use least restraint required—increased restraint 
increases stress. • If greater restraint needed, use 
gentle, balanced pressure with global support. 
• Prevent flailing by controlling head/rear. 
• Avoid lateral recumbency—only if procedure 
requires. • Avoid multiple bouts of restraint—
adjust positioning by sliding hands along body. 
• Struggling 3 seconds—stop, reposition, try 
again; wait for dog to relax to begin. • Second 
attempt—if fear increases or starts to get 
fractious, stop; is procedure essential? 
• Essential—use chemical restraint. 
• Nonessential:—send home with handling plan 
and pre-visit meds if indicated for return visit.
Expedite procedures by reducing dog fear, 
minimizing manual restraint, and increasing 
safety.
Music
Music and sources of white noise may mask 
stressful external sounds. Classical music may relax 
dogs and have calming effects on clients and staff.
Dog-Appeasing Pheromone (Adaptil®)

Canine and Feline, Seventh Edition  493
F
FMuzzles
• For safety, assessment/evaluation, avoid 
human fear response, injectable sedation. 
• Home desensitization (DS)/CC—enters 
wearing comfortably. • Basket muzzle 
preferred—allows panting: safer for longer 
procedures/kenneling; allows CC: inserted food 
or smeared along inside. • Nylon sleeve—short 
procedures or facilitate essential injection.
Elizabethan Collar
Muzzle alternative for avoiding/reducing 
visual stimuli.
Towels
• Towels/thick bedding can help immobilize—
especially small dogs: head/body control, 
reduced visual stimuli, global pressure. • Roll 
towels (cervical collar)—head control.
Eye Covers (e.g., ThunderCap®)
Reduce visual stimuli/triggers for fear and 
anxiety during travel, exam, injections.
Compression Garments (e.g., 
ThunderShirt®)
Swaddles—may relax patients with balanced 
body pressure.
N/A
ACTIVITY
N/A
DIET
N/A
Preventive counseling at first puppy visit ± 
puppy classes in clinic to review positive travel, 
handling, communication, reward training, and 
avoiding punishment. See Internet Resources.
N/A
• Allows safe, effective, minimal handling and 
successful completion of procedures. • Blocks or 
prevents distress, discomfort, pain, escalation, 
and fear sensitization. • Injectable sedation 
(IM)—most effective for safe handling 
fractious/fearful dogs. • Base protocol on age, 
temperament, health. • Pre-travel oral sedative/
anxiolytics reduce fear, facilitate gentle handling, 
• Administer 1.5–2 hours pre-travel for mild/
moderate fear or to facilitate restraint injection; 
may give first dose 12 hours in advance; repeat 
dosing as needed if patient is hospitalized. 
• T razodone—4.0–10 mg/kg (up to 18 mg/kg); 
maximum 300 mg per dose. • Clonidine—  
0.01–0.05 mg/kg. • Dexmedetomidine 
oromucosal gel—125  μg/m2. • Gabapentin—  
20–50 mg/kg. • Lorazepam—0.05–0.5 mg/kg. • Diazepam—0.5–2.2 mg/kg. • Alprazolam—  
0.01–0.1 mg/kg. • For additional sedation can 
add acepromazine—0.55–2.2 mg/kg. • Can 
combine trazodone, clonidine, gabapentin, 
benzodiazepines. • Avoid acepromazine as sole 
agent—ineffective anxiolysis
Injectable Restraint
• Young/healthy —dexmedetomidine 10–20  μg/
kg + opioid: for additional sedation can add 
ketamine 3–5 mg/kg IM. • Alternative —
tiletamine/zolazepam 5–10 mg/kg IM (not 
practical for dogs >20 kg due to volume). 
• Geriatric/ill— acepromazine 0.01–0.05 mg/kg 
or dexmedetomidine 5–10  μg/kg + opioid: for 
additional sedation add ketamine 2–5 mg/kg 
IM; alfaxalone 1–2 mg/kg (not practical for dogs 
>10 kg due to volume) + midazolam 0.2 mg/kg 
± opioid ± acepromazine 0.01–0.05 mg/kg. 
• Can reverse dexmedetomidine—equivolume 
atipamezole to volume of dexmedetomidine IM. 
avoid dysphoria wait 45–60 min to reverse; 
opioid choices (full Mu agonist superior for pain 
control): butorphanol 0.2–0.4 mg/kg; morphine 
0.2–0.4 mg/kg; hydromorphone 0.05–0.2 mg/
kg; methadone 0.3–0.5 mg/kg.
Oral Transmucosal (OTM)
• Young/healthy —dexmedetomidine 10–40 
μg/kg ± opioid (e.g., morphine 10 mg/kg or 
butorphanol 0.2 mg/kg) OTM; can reverse 
dexmedetomidine with atipamezole (½ volume of 
dexmedetomidine). • DS/CC to syringe in buccal 
pouch. • Up to 1h to effect. • Mucosal contact 
time improves absorption—mix with syrup.
Avoid clonidine with cardiovascular output issues.
• Have client perform oral medication trial at 
home to determine dose/response. • Agitation, 
gastrointestinal upset, sedation, appetite changes 
possible. • Benzodiazepines—disinhibition of 
aggression possible. • Gabapentin—caution 
with chronic renal disease.
Avoid combining oral acepromazine with 
clonidine—potential blood pressure fluctuation.
Natural products including pheromones, 
alpha-casozepine and calming probiotic.
  FOLLOW-UP
• Evaluate and monitor physiologic/
behavioral parameters. • Maintain record 
of response to handling, location, personnel, 
products, and drugs.
improved healthcare compliance, and avoids fear 
sensitization. • Also see Client Education.POSSIBLE COMPLICATIONS
Dogs with fearful and/or aggressive behavior may 
not receive adequate veterinary care including 
wellness care, diagnostics, and treatment.
Stress care prevents and reduces fear, anxiety, 
and stress and improves frequency and quality 
of veterinary care.
Dogs with fearful/fractious behavior in veterinary 
setting often have comorbid behavioral problems, 
including aggression to owners or strangers, leash 
reactivity, resource guarding, anxiety disorders.
• Socialization period (3–12 weeks)—sensitive 
period where positive exposure minimizes fear; 
gentle, brief handling paired with positive 
experience (food) leads to less fear and improved 
handling. • Fear period (8–10 weeks of age and 
between 4 and 11 months)—susceptible to 
single-event learning, highly sensitive to negative 
experiences. • Social maturity (1–3 years)—
fearful puppies/adolescents may begin to show 
fear and aggression at this time; prompt 
recognition and intervention essential at first 
signs of fear to establish handling plan.
Fearful/aggressive temperaments heritable.
SYNONYMS
SEE ALSO
• Puppy Socialization and Puppy Classes.
• HPA = hypothalamic pituitary axis.
how-to-prepare-your-pet-for-vet-visit/
how-to-make-trip-to-vet-fear-free/ • https://
fearfreehappyhomes.com/courses/dog-body-
language-101 • http://www.fearfreepets.com 
• https://lowstresshandling.com/
Vet Clin Small Anim 2014, 44:451–481.
Consulting Editor  Gary M. Landsberg(continued)  Fear and Aggression in Veterinary Visits—Dogs

F494  Blackwell’s Five-Minute Veterinary Consult  
FFears, Phobias, and Anxieties—Cats
  BASICS
• Fear is the feeling of apprehension resulting 
from the nearness of some situation or object 
presenting an external threat. The response of 
the autonomic nervous system prepares the 
body for “freeze, fight, or flight.” As such, it is 
a normal behavior, essential for adaptation 
and survival.
• Anxiety is the anticipation of dangers from 
unknown or imagined origins that results in 
physiologic reactions associated with fear. 
Anxiety may occur in the aftermath of a 
fear-producing event or as a result of 
unrelated environmental changes that are 
unpredictable.
• A phobia is a persistent and excessive fear of 
a specific stimulus, such as a thunderstorm or 
separation from an attachment figure.
• Stress responses become problematic when 
the individual is not able to control the 
stressful situation by their actions or escape 
from it through appropriate behavioral 
• Chronic anxiety or fear can lead to 
secondary behavior problems, such as 
overgrooming, spraying, or intercat 
aggression, or predispose the cat to health 
problems owing to a compromised immune 
system.
• Behavioral—hypervigilance, avoidance 
behaviors, possible aggression.
• Cardiovascular—increased heart rate and 
blood flow to internal organs during 
fear-evoking incidents.
• Endocrine/metabolic—glucose release into 
bloodstream, release of glucocorticoids.
• Gastrointestinal (GI)—decreased appetite.
• Musculoskeletal—weight loss in response to 
chronic stress effects on appetite, decreased 
food intake due to hiding behavior.
• Neuromuscular—decrease in activity due to 
avoidance and hiding; fearful/anxious 
reaction may also include pacing, trembling, 
repetitive activity.
• Respiratory—increased respiratory rate 
when anxious or frightened.
• Skin/exocrine—overgrooming in response 
to stressors.
GENETICS
• Genetic component possible.
• Breed/coat color and paternal personality 
have been linked to individual personality 
traits in cats.SIGNALMENT
Any age, sex, or breed.
SIGNS
• Signs of fear or anxiety can vary between 
individuals and with different stimuli that 
may be specific (a particular individual, 
sound, etc.) or more generalized.
• In mild cases of anxiety or fear the cat may 
become tense and more reactive to environ -
mental stimuli. Some individuals may retreat 
to perceived safe hiding places or show little 
movement.
• Cats in panic can become very aggressive or 
destructive in an attempt to retreat from the 
fearful stimulus.
• Clear description of the cat’s body language, 
behavior, and events or situations that 
consistently trigger anxiety or fear is helpful 
in setting up behavioral modification and 
environmental management program.
• Body postures associated with fearful 
behavior include ears flattened to back or side 
of head, crouched body posture when resting 
or moving, lowered head, tail tucked 
alongside body or held low, piloerection, 
dilated pupils, shaking, panting, drooling, 
“Halloween cat” silhouette.
• If fear is intense, cat may lose bladder and 
bowel control and express its anal sacs.
• Vocalizations are usually minimal, unless 
cat is showing defensive behavior in response 
to perceived threat.
• Cat may pace, vocalize, and solicit attention 
from owner.
• Urine spraying and destructive scratching 
may be seen in anxious cats.
Usually unremarkable unless cat has injured 
itself trying to escape or while seeking shelter.
Fearful behavior in cats can be related to 
genetic influences on temperament; lack of 
positive early experience and socialization, 
observational learning from fearful mother, 
other adult cats; learning from negative 
experiences; social stress, population 
pressure.
  DIAGNOSIS
Thorough medical history and physical 
examination will help differentiate fearful 
behavior from withdrawal due to illness.
As indicated to rule out medical conditions 
and as baseline prior to medication use and as 
premedication screen.OTHER LABORATORY TESTS
As indicated, including T4 in middle age and 
older.
IMAGING
As indicated.
  TREATMENT
ACTIVITY
Normal social interactions and play should be 
encouraged, but contact should not be forced.
DIET
Placement of food, water, and litter box may 
need to be altered if anxious or fearful 
behavior is limiting access.
• Educate owners to read and understand cat 
communication language for early recognition 
of signs.
• Discuss behavioral expectations. Owner 
expectations in regard to social interactions 
with humans or other cats may be contributing 
to the problem and could affect prognosis.
• T reatment plan involving case-tailored 
behavioral modification, environmental 
adjustments, and support material will help 
owner better understand situation and 
implement treatment.
Behavioral Therapy
• Identify and avoid exposure to fear-evoking 
stimuli and situations. Provide ways for cat to 
manage situation by creating “safe places” for 
cat to go to avoid the stimulus.
• If cat must be handled while fearful, caution 
and gentle physical restraint aids (cat muzzles, 
head covers, towel wraps, etc.) should be used 
to prevent injury and decrease stress.
• Desensitization and counter-conditioning 
to help decrease reactivity to fear-producing 
stimulus. Systematic desensitization is 
program of slowly increasing exposure to 
fearful stimulus or situation. Counter-
conditioning consists of enhancing internal 
and external environment with food rewards 
or other pleasurable stimuli such as playing 
with toys.
• Address secondary problems such as 
strained social interactions subsequent to 
defensive aggression directed toward humans 
or other cats, or elimination problems that 
may be result of fears or anxieties.
• Medication can be helpful adjunct to 
behavioral modification, if animal’s fearful or

Canine and Feline, Seventh Edition  495
F
Fanxious behavior is so intense that it interferes 
with quality of life.
• No drug is approved by FDA for use in cats 
for fearful behavior; therefore, clients must be 
advised that information concerning efficacy, 
contraindications, and side effects is limited.
• If there are questions or concerns about a 
specific patient or medication, consultation 
with a veterinary behaviorist may be helpful.
(SSRIs)—fluoxetine or paroxetine 0.5–1 mg/
kg PO q24h. Side effects—decreased appetite 
and irritability; paroxetine has anticholinergic 
effects.
• T ricyclic antidepressants (TCAs)—
clomipramine 0.5 mg/kg PO q24h 
(2.5–5 mg/cat). Side effects—sedation, 
anticholinergic effects, possible cardiac 
conduction disturbances in predisposed 
animals.
• Buspirone—0.5–1.0 mg/kg q8–24h. Side 
effects—GI upset, mild sedation.
• Benzodiazepines—oxazepam 0.2–0.5 mg/kg 
q12–24h; alprazolam 0.125–0.25 mg/cat q12h 
or as needed prior to event; lorazepam 
0.025–0.05 mg/kg (or 0.125–0.5 mg/cat) 
q12h or as needed prior to event. Side effects—  
sedation, increased appetite, agitation.
• Buspirone and benzodiazepines might 
reduce fear and build confidence in fearful cat 
that does not retaliate or fight back.
• Cats with renal or hepatic disease.
• Caution with TCAs and SSRIs in diabetics.
• TCAs in patients with cardiac abnormalities.
• Laboratory screening tests suggested before 
placing animal on psychotropic medication 
for health assessment and baseline for 
comparison.
• Compounding medications in more 
palatable form can ease administration and 
improve compliance.
• Assess all medications and natural 
supplements being administered for potential 
contraindications.
• TCAs and SSRIs should not be used together.
• Mirtazapine should be used cautiously in 
combination with TCA or SSRI.• Practitioner should verify safety when 
combining psychoactive drugs with other 
• Natural products that might aid in reducing 
anxiety alone or in conjunction with drugs— 
S-adenosylmethionine (SAMe) 100 mg PO 
q24h; alpha-casozepine 75 mg (15 mg/kg or 
greater) PO q24h; l-theanine 25 mg PO daily.
• Cat-appeasing pheromone (Feliway® 
Multicat or Friends); F3 cheek gland 
pheromone (Feliway).
• Calming and stress diets containing 
alpha-casozepine and l-tryptophan.
  FOLLOW-UP
Frequent follow-up either in person or by 
telephone is necessary, especially during first 
few months of treatment, to motivate client 
and monitor effectiveness of any adjunct drug 
• Early socialization to people, places, and things 
up to 7 weeks of age, and ongoing positive 
exposure during first year, may help prevent 
some later problems with fearful behavior.
• Calm interactions and positive associations 
with fear-producing stimuli may help keep 
fear-based reactions to minimum.
Secondary behavior problems may arise or 
persist after fearful or anxious behavior has 
diminished and will need specific treatment.
• Realistic “end point” depends on animal’s 
background (socialization history, genetic and 
individual differences in personality), home 
situation, and other confounding factors such 
as frequency of natural exposure to fear-
producing stimuli.
• Medication may improve but not totally 
ameliorate signs.  MISCELLANEOUS
• Stereotypic or compulsive disorders.
• Urine marking, inappropriate elimination.
• Defensive aggression directed toward 
humans, other animals; may also make cat 
target for aggression from other cats.
N/A except for bite and scratch wounds.
Drug use in pregnant animals should be avoided.
SEE ALSO
Cats.
• Housesoiling—Cats.
Behavior—Cats.
• https://www.catvets.com
Herron, M. E., Horwitz, D., Siracusa, C., & 
Dale, S. (2020). Decoding your cat: The 
ultimate experts explain common cat 
behaviors and reveal how to prevent or 
change unwanted ones. Boston: Houghton 
Mifflin Harcourt.
ed. Edinburgh: Saunders Elsevier, 2013.
Levine ED. Feline fear and anxiety. Vet Clin 
North Am Small Anim Pract 2008, 
38(5):1065–1079.
Overall KL. Manual of Clinical Behavioral 
MO: Elsevier Mosby, 2013.
Author  Leslie Larson Cooper
Consulting Editor  Gary M. Landsberg(continued)  Fears, Phobias, and Anxieties—Cats

F496  Blackwell’s Five-Minute Veterinary Consult  
FFears, Phobias, and Anxieties—Dogs
  BASICS
• Fear—an emotion consisting of a 
physiologic stress response (PSR) and a 
psychologic response to the presence of a 
stimulus perceived as dangerous (e.g., person, 
animal, situation, sound, object, scent) 
inducing an adaptive, avoidance reaction. 
• Phobia —marked, irrational, and excessive 
fear of a stimulus (e.g., animal, situation, 
person, sound, object, scent) consisting of a 
PSR and psychologic response resulting in a 
maladaptive reaction. •  Anxiety —reaction 
consisting of a PSR and psychologic response 
triggered by anticipation of future or memory 
of past dangers.
• Information about a fear-inducing stimulus 
is perceived by sensory organs and transmitted 
to the central nucleus of the amygdala; the 
central nucleus sends output to the central grey 
matter (musculoskeletal response), lateral 
hypothalamus (autonomic nervous system 
[ANS] response), and stria terminalis 
(hormonal response) causing a PSR. •  The 
PSR is graded based on the animal’s perceived 
level of control, coping strategy, and level of 
difficulty. •  Any neutral stimulus in the 
environment can be paired with the PSR 
through classical conditioning triggering a PSR 
to the conditioned stimulus. •  Hormones and 
neurotransmitters released during the PSR 
enhance learning, memory consolidation, and 
retrieval. •  There is evidence that while 
frightening memories can be significantly 
reduced, they cannot be “erased.”
• Psychologic—immobility, restlessness, 
pacing, circling, hyperattachment, escape, 
avoidance, approach/retreat, destructiveness, 
vocalization, aggression. •  Cardiovascular—
tachycardia, hypertension. •  Endocrine/
metabolic—alterations in hypothalamic 
pituitary–adrenal axis, increased blood 
glucose. •  Gastrointestinal—inappetence, 
hypersalivation, vomiting, diarrhea, 
defecation. •  Hemic/lymphatic/immune—
stress leukogram. •  Musculoskeletal— 
self-injury. •  Neurologic—increased motor 
activity, trembling, decreased pain perception, 
catatonia, partial seizure. •  Ophthalmic—
episcleral injection, mydriasis. •  Renal/
urologic—urination. •  Respiratory—
tachypnea. •  Skin/exocrine—traumatic 
injury, acral lick dermatitis (ALD).
GENETICS
Heredity influences development of fears and 
phobias, although unclear at this time to what 
extent specific fears (e.g., noise) are heritable.INCIDENCE/PREVALENCE
• Separation anxiety—13–40%. •  Sound 
aversion, fear, and phobia—up to 50%. 
• General fearfulness—26%. •  Reactivity to 
people—7%. •  Fear of veterinarian—up to 
78.5%.
No age, breed, or sex overrepresented.
SIGNS
Hypervigilance, ANS arousal, catatonia, 
increased motor activity, elimination, 
destruction, vocalization, hypersalivation, 
panting, hiding, trembling, escape behaviors, 
fearful body language.
T raumatic experience, inadequate 
socialization, fearful/anxious dam or sire, 
history of inability to escape stimulus 
(e.g., locked in crate).
May be unremarkable; self-induced injuries 
possible.
CAUSES
• Inadequate socialization, traumatic event, 
hereditary, cognitive dysfunction syndrome 
(CDS), previous learning. •  Illness or pain 
may contribute to development of fears, 
phobias, and anxieties.
General—existing fears, anxieties, and phobias; 
inadequate socialization, rehoming, anxious/
fearful/physically ill dam, traumatic event.
  DIAGNOSIS
• Psychologic—CDS; incomplete 
housetraining; urine/fecal marking; territorial 
aggression; separation-related disorders; 
attention-seeking; storm, noise, or 
environmental phobias; generalized anxiety; 
neophobia; fear-induced aggression. 
• Medical—neoplasia (e.g., intracranial), 
endocrinopathy (e.g., Cushing’s, 
hypothyroidism), cystitis, pyelonephritis, 
diabetes, gastrointestinal disease (e.g., 
inflammatory bowel disease), neurologic 
disease (e.g., seizures), dermatologic 
(e.g., ALD, atopy, food allergies), toxicity 
(e.g., lead, recreational drugs).
Perform before initiating drug treatment.
• Thyroid status. •  Adrenal tests if indicated 
by history, signalment, physical examination, 
and laboratory tests.IMAGING
CT or MRI if indicated to rule out CNS 
disorder. Other imaging if indicated (e.g., pain).
• Thorough behavioral history and 
observation of patient (video of behavior is 
helpful). •  Exposure to stimulus if safe.
  TREATMENT
• Typically outpatient. •  Inpatient 
(dayboarding/daycare)—if fear-/anxiety-/
phobia-inducing stimulus unavoidable, 
patient causing self-injury, medication not yet 
effective, hospitalization to stabilize patient on 
medication. •  T reatment includes owner 
education, safety, behavior modification to 
change emotional state of patient, 
environmental modification to avoid triggers 
and distract patient during episodes, reduction 
of anxiety. •  Diagnose and treat any 
conditions that may cause pain, discomfort, or 
changes in mood as well as any injuries.
Safety
• Owner—should not push, pull, grab, or 
reach for dog showing clinical signs, as this 
can result in owner-directed aggression; 
instead, use food or toy to move patient. 
• Patient—if intense escape attempts or 
self-injury are present, avoid crating and limit 
dog’s access to windows, doors, electrical 
wiring, and water lines; consider dayboarding. 
• Public—avoid situations where stimulus is 
present until treatment is complete.
• Avoid stimulus for 2–8 weeks depending on 
severity of reaction while teaching coping skills 
to patient (e.g., sit, watch, look at that, leave it, 
relaxation) and setting up safe spot. •  Structured 
interactions with owner (e.g., sit for all 
interactions). •  Independence exercises—down/
stay with food toy. •  Punishment (e.g., shock/
choke collar correction, yelling, hitting) 
contraindicated. •  Client should distract dog 
and redirect to play or food toy when frightened 
or anxious. •  Desensitization and counter-
conditioning (DS/CC)—can begin after coping 
tools have been taught; can be attempted with 
supervision of highly qualified positive 
reinforcement trainer or veterinary behavior 
technician; DS/CC can sensitize animal to 
stimulus, causing behavior disorder to worsen.
• Create safe spot/safe haven where exposure 
to fear-producing stimulus can be limited. 
• Consider dayboarding/daycare. •  Limit use 
of crate until dog uses readily and does not panic 
when confined. •  Environmental enrichment 
(e.g., rotate toys, food toys, exercise).

Canine and Feline, Seventh Edition  497
F
Behavior treatment appointments can be 
scheduled with veterinary technicians. Consider 
short-term or day boarding for regulation of 
medications or avoidance of stimulus.
ACTIVITY
• Increased exercise will act as environmental 
enrichment for patient but will not significantly 
lower anxiety/fear disorders. •  Exercise should 
avoid any exposure to fear-inducing stimulus.
• Advise owners that patient is not spiteful or 
guilty; may be long course of treatment; will 
most likely be managed, not cured. •  Help 
client understand subtlety of signs involved 
and learn to recognize signs associated with 
fear, anxiety, and stress.
• Should always be prescribed with complete 
treatment plan in order to be compliant with 
standard of care. •  Most treatment will be long 
term, possibly years; minimum treatment 
generally 6 months with concurrent behavior 
modification; if dog has significantly improved 
in 6 months, try slow weaning by reducing dose 
by 25–50% every 14 days. •  Situational, mild 
PRN drug indicated, e.g., benzodiazepine, 
serotonin reuptake inhibitor/antagonist (SARI) 
either alone if stimulus is occasional and 
predictable, or more commonly concurrent with 
selective serotonin reuptake inhibitor (SSRI) or 
tricyclic antidepressant (TCA) prior to event. 
◦ Best administered before any signs of 
anxiety, fear, or panic; minimally 60–90 min 
before anticipated provocative stimulus. 
◦ Benzodiazepines—diazepam 0.50–2 mg/kg 
PO up to q8h; clorazepate 0.50–2 mg/kg PO up 
to q6h; alprazolam 0.01–0.1 mg/kg PO up to 
q4h. ◦ SARI: trazodone 3.0–10 mg/kg PO up 
to q8h (up to 15 mg/kg). ◦ Alpha-2 agonist—
clonidine 0.01–0.05 mg/kg PO up to q8h. 
• Dexmedetomidine oromucosal gel—125  μg/
m2 onto oral mucosa 30–60 min prior to fear-  
evoking event. •  Generalized, stimulus 
unavoidable or severe—daily administered drug 
indicated. ◦ Both TCAs and SSRIs can take up 
to 6 weeks to take effect; start at low end of 
dosing range and then slowly increase in 
2–4-week increments based on response to avoid 
side effects. ◦ TCA—clomipramine 1.0–3.0 mg/
kg PO q12h. ◦ SSRI—sertraline 1.0–3.0 mg/kg 
PO q24h; fluoxetine or paroxetine 0.5–2.0 mg/
kg PO q24h.
• All listed medications are extra-label except 
clomipramine and fluoxetine for treatment of 
separation anxiety and dexmedetomidine 
oro-mucosal gel for noise aversion in dogs in 
the United States—follow Health and Human Services recommendations. •  Cardiac 
conduction anomalies—use caution and 
monitoring when giving TCAs. •  Use 
caution when prescribing drugs to geriatric 
patients or patients with hepatic or renal 
compromise—review metabolism and 
elimination of medication before prescribing. 
• Clients should receive drug information 
handouts with potential side effects listed. 
• Mood-altering medications have potential 
to increase agitation, fear, and aggression.
• Use caution when prescribing multiple 
medications concurrently that have same 
mode of action; review drug monographs 
for each drug before prescribing. •  Do not 
use SARIs, SSRIs, or TCAs with monoamine 
oxidase inhibitor (MAOIs), including 
but not limited to selegiline and amitraz. 
• Do not use SSRIs and TCAs together—
possible risk of serotonin syndrome, which 
can be fatal.
Buspirone (daily)—0.5–1.0 mg/kg BID–TID.
Natural products that may aid in reducing 
anxiety—dog-appeasing pheromone 
(Adaptil®); alpha-casosopene (Zykene®) alone 
or in diet together with l-tryptophan (Royal 
Canin Calm® diet); l-theanine alone 
(Anxitane®) or in combination product 
containing whey protein, Phellodendron 
amurense , and Magnolia officinalis  (Solliquin®); 
melatonin; S-adenosylmethionine (SAMe); 
Souroubea and Plantanus (Zentrol®), or a 
probiotic supplement (Calming Care®).
  FOLLOW-UP
• Clients should contact veterinary healthcare 
team with updates at 2-week intervals for first 
6–8 weeks of treatment; typically, treatment 
plan will have to be altered. •  CBC, biochemistry, 
urinalysis, T4, fT4, q12 months for animals 
<8 years on daily administered medications; 
senior dogs may require more frequent 
reassessment based on age and health.
• Proper socialization—8–12 weeks, 
including puppy classes starting at 8 weeks. 
• Structured relationship with owner (e.g., sit 
for all interactions). •  Basic obedience. 
• T reat traumatic experiences immediately.
If left untreated or treated with medication 
only, worsening clinical signs likely.
• Depends on response to medication, 
suitability of environment, and client’s 
ability to perform behavior modification. • T reatment duration varies from 2 to 12 
months depending on severity and number 
of problems; only dogs who respond well 
to behavior modification and 
environmental management can be 
expected to be weaned off medication. 
• Typically, treatment will continue to 
some extent throughout dog’s life.
CDS can present as nonspecific fear.
Most listed medications are not evaluated in 
or contraindicated in pregnant animals.
SYNONYMS
• Generalized anxiety. •  Neophobia.
SEE ALSO
• Aggression – Overview Dogs.
• Fear and Aggression – Veterinary Visits Dogs. 
• Thunderstorm and Noise Phobias – Dogs.
• ALD = acral lick dermatitis.
• ANS = autonomic nervous system.
• DS/CC = desensitization and counter- 
• PSR = physiologic stress response.
• SARI = serotonin reuptake inhibitor/antagonist.
• https://www.dacvb.org •  https://avsab.org 
dog-body-language-101
Becker M, Radosta L, Sung W, et al. From 
Fearful to Fear Free. Irvine, CA: Lumina 
Media, 2017.
Behavior, 2nd ed. Chichester: Wiley, 2018, 
pp. 253–388.
Horwitz D, Mills D, eds. BSAVA Manual of 
Canine and Feline Behavioural Medicine, 
2nd ed. Gloucester: BSAVA, 2009.
Author  Lisa Radosta
available online(continued)  Fears, Phobias, and Anxieties—Dogs

498  Blackwell’s Five-Minute Veterinary Consult  
FFeline Alveolar Osteitis
  OVERVIEW
Thickening of bone over the jugum of tooth 
roots due to inflammation. Alveolar osteitis 
most commonly occurs over the maxillary 
canine tooth roots of middle-aged and older 
cats (sometimes also called buttressing). This 
process appears to be secondary to 
periodontal inflammation. Tooth resorption 
and extrusion (supereruption) may also be 
seen in affected teeth. Feline alveolar osteitis 
should be distinguished from benign alveolar 
bone expansion (also called buccal bone 
expansion), which is devoid of inflammation.
Although alveolar osteitis can occur in dogs, 
it is far more common in cats. There are no 
established breed or sex predilections, and no 
established genetic basis. Middle-aged and 
older cats are most commonly affected.
SIGNS
History
• Owner may report thickening or bulging 
over the maxillary canine teeth roots, usually 
bilateral, but can be unilateral.
• Evidence of oral pain is not often noted by 
pet owners.
◦ Discomfort may occur with mobile teeth.
◦ Discomfort may occur when extruded 
maxillary canine teeth contact the lower lip 
or the opposing canine, resulting in an 
acquired malocclusion.
Clinical Findings
• Bulging of alveolar bone on the buccal 
surface of the root; variable degree of gingival 
• Patient may have abnormal periodontal 
pocket depths on probing (normal sulcus depth 
for cats is 0–1 mm); patients often exhibit 
vertical bone loss with infrabony pockets.
• Patients may exhibit extrusion (supereruption) 
of one or more teeth; extended tooth length 
may cause trauma to lower lip or malocclusion 
with opposing mandibular canine tooth.
• May progress to tooth mobility and acquired 
dental malocclusion due to contact between 
maxillary and mandibular canine teeth.
Cause is unknown, but buttressing in humans 
is considered to be an attempt by the body to 
stabilize a diseased tooth. Cats that are prone 
to periodontal disease may be at a higher risk 
for developing alveolar osteitis.
  DIAGNOSIS
Alveolar bone expansion, also known as buccal 
bone expansion, is an enlargement of alveolar bone that looks similar to alveolar osteitis. 
However, when biopsied, alveolar bone 
expansion may show no signs of inflammation.
No specific abnormalities seen related to 
alveolar osteitis.
IMAGING
Intraoral dental radiographs typically show 
evidence of vertical periodontal bone loss 
along the long axis of the root on the palatal 
and buccal surface of the root. The expanded 
bone may be less dense than normal adjacent 
alveolar bone.
• Appropriate preanesthetic diagnostics when 
• Complete oral examination with periodontal 
probing—assess for periodontal pockets, 
gingival bleeding or tooth mobility; pay 
particular attention to probing depth of 
palatal surface of maxillary canine teeth.
• Intraoral radiographs under anesthesia—
assess extent of osseous changes; assess root 
stability, attachment loss, and evidence of 
tooth resorption.
• Consider biopsy if bone changes are 
unilateral or if aggressive osseous changes are 
seen on dental radiographs.
 TREATMENT
• If mild periodontal changes are present 
(moderate pocket depth, no tooth mobility, 
minimal extrusion, no oronasal fistulation), a 
professional ultrasonic dental cleaning with 
root planing and subgingival curettage ± 
placement of periodontal pocket antimicrobial 
treatment ± osseous surgery.
• If extensive periodontal disease is present 
(deep periodontal pocket, tooth mobility, 
extensive extrusion, patient discomfort, oronasal 
fistula), consider extraction. Buccal attached 
gingiva may be very thin, making it difficult to 
elevate a gingival flap. Ostectomy/osteoplasty of 
buccal alveolar bulge is necessary after raising 
the gingival flap and prior to closure. Biopsy of 
buccal alveolar bone can be accomplished with 
rongeurs once a mucogingival flap has been 
elevated. Gently elevate palatal mucosal edge to 
facilitate closure.
Appropriate antimicrobials and pain 
medications when indicated.
Recheck patient at 2 weeks postoperatively, 
with regular reevaluations depending on what 
treatment was chosen.
No known methods of prevention.
Complications include those that may occur 
when extracting teeth (perforation of 
mucogingival flap, dehiscence, iatrogenic 
oronasal fistula, etc.).
Good with appropriate treatment, unless 
neoplasia is diagnosed with biopsy.
Beebe DE, Gengler WR. Osseous surgery to 
augment treatment of chronic periodontitis 
of canine teeth in a cat. J Vet Dent 2007, 
24(1):30–38.
Author  John R. Lewis

Canine and Feline, Seventh Edition  499
FFeline Calicivirus Infection
  BASICS
A common viral respiratory disease of 
domestic and exotic cats characterized by 
upper respiratory disease and oral ulceration, 
occasionally pneumonia or arthritis, and 
rarely a highly fatal systemic hemorrhagic 
disease (FCV–VSD).
• Spread through ocular, nasal, and oral 
• T ransmission typically occurs through 
direct contact or fomite exposure; droplet 
transmission possible within 4–5 feet; 
replication takes place primarily in respiratory 
and oral tissues.
• Rapid cytolysis of infected cells results in 
tissue pathology and clinical disease.
• Gastrointestinal—ulceration of the tongue 
common; occasional ulceration of the hard 
palate and lips.
• Hemic/lymphatic/immune—hemorrhage; 
splenic necrosis (FCV–VSD).
• Hepatobiliary—hepatic necrosis (FCV–
VSD).
• Musculoskeletal—acute arthritis.
• Ophthalmic—acute serous conjunctivitis 
without keratitis or corneal ulcers.
• Respiratory—rhinitis; interstitial 
pneumonia; ulceration of nose tip.
• Skin/exocrine—subcutaneous edema; 
ulcerations of pinnae or pawpads; pancreatic 
necrosis (FCV–VSD).
GENETICS
None
• Persistent infection common, resulting in 
virus-shedding carriers.
• Clinical disease—common in multicat 
facilities, shelters, breeding catteries.
• Routine vaccination—reduces incidence 
and severity of clinical disease; has not 
decreased prevalence of the virus.
Worldwide
Species
Cat
None
• Young kittens >6 weeks old—most 
common.
• Cats of any age may show clinical disease.
NoneSIGNS
Severity of disease is dependent on host 
immune status, virulence of infecting strain, 
and presence of co-infections. Most common 
manifestation involves self-limiting upper 
respiratory tract disease and oral ulceration.
• Sudden onset.
• Serous ocular or nasal discharge, usually 
with little or no sneezing.
• Ulcers on tongue, hard palate, lips, tip of 
nose, or around claws.
• Dyspnea from pneumonia.
• Acute, painful lameness.
• Ranging from generally alert and in good 
condition to lethargy and decreased 
• Fever.
• Ulcers of tongue/mouth may occur without 
other signs.
• Upper to lower respiratory tract disease—
nasal discharge, or stertor; wheezes, crackles, 
or increased bronchovesicular sounds on 
pulmonary auscultation,
• Epistaxis or hematochezia with systemic 
hemorrhage (FCV–VSD).
• Facial and limb edema with crusting/
ulcerations of face, pinnae, and feet due to 
vasculitis (FCV–VSD).
• Icterus (FCV–VSD).
CAUSES
• A small, nonenveloped single-stranded 
RNA virus, feline calicivirus (FCV).
• Numerous strains exist in nature, with 
varying degrees of antigenic cross-reactivity.
• More than one serotype.
• Relatively stable and resistant to many 
• Lack of vaccination or improper 
• Multicat facilities.
• Concurrent infections with other 
pathogens, e.g., feline herpesvirus (FHV), 
feline panleukopenia virus (FPV), feline 
leukemia virus (FeLV).
• Poor ventilation.
• Stress.
  DIAGNOSIS
• FHV.
• Chlamydiosis.
• Bordetella bronchiseptica .CBC/BIOCHEMISTRY/URINALYSIS
No characteristic or consistent findings.
Often diagnosed on clinical signs.
IMAGING
Radiographs of lungs—consolidated lung 
tissue in cats with pneumonia.
• PCR—oropharyngeal swabs most likely to 
detect virus; positive result does not prove 
that FCV is causative agent for disease due to 
persistently shedding cats.
• Cell cultures to isolate virus—oral pharynx; 
lung tissue; feces; blood; secretions from nose 
and conjunctiva.
• Immunofluorescent assays of lung 
tissue—viral antigen.
• Serologic testing on paired serum samples—
detect rise in neutralizing antibody titers 
against virus; vaccination interferes with 
results from serum neutralization testing.
• Gross—upper respiratory infection; ocular 
and nasal discharge; pneumonia with 
consolidation of large portions of individual 
lung lobes; possible ulcerations on tongue, 
lips, and hard palate; systemic hemorrhages.
• Histopathologic—interstitial pneumonia of 
large portions of individual lung lobes; 
ulcerations on epithelium of tongue, lips, and 
hard palate; mild inflammatory reactions in 
nose and conjunctiva; systemic hemorrhages, 
vasculitis, or necrosis.
  TREATMENT
Outpatient, unless severe pneumonia, 
hemorrhage, or severe systemic disease.
• Clean eyes and nose as indicated with warm 
• Provide access to steam, such as in a 
bathroom, to clear secretions.
• Provide palatable, soft foods.
• Oxygen—with severe pneumonia.
ACTIVITY
Patients should be restricted from contact 
with other cats to prevent transmission of 
causative virus.
DIET
• Soft foods—if ulcerations restrict eating.
Discuss need for proper vaccination and to 
modify vaccination protocol in breeding 
catteries to include kittens before they

500  Blackwell’s Five-Minute Veterinary Consult  
Fbecome infected (often at 6–8 weeks of age) 
from a carrier queen.
None
• No specific antiviral drugs are clearly 
• Broad-spectrum antibiotics—indicated for 
treatment of secondary bacterial infections 
(e.g., amoxicillin or amoxicillin–clavulanate 
at 22 mg/kg PO q12h; doxycycline at 5 mg/
kg PO q12h).
• Secondary bacterial infections of affected 
cats not nearly as important as with FHV-1 
• Antibiotic eye ointments—to reduce 
secondary bacterial infections of conjunctiva.
• Pain medication—as indicated for arthritis 
pain or significant ulceration.
None
None
None
None
  FOLLOW-UP
• Monitor for sudden development of 
dyspnea associated with pneumonia.
• No specific laboratory tests.
Practitioners—classifies FHV, FPV, and FCV 
as core vaccines; vaccinate all cats with either 
a modified live virus (MLV) or inactivated 
core vaccine on initial visit (as early as 6 
weeks of age), repeat every 3–4 weeks until 16 
weeks of age, and booster 1 year after last 
kitten vaccine; revaccinate every 3 years.
• Breeding catteries—respiratory disease is a 
problem; vaccinate kittens at earlier age, 
either with additional vaccination at 4–5 
weeks or with intranasal vaccine at 10–14 days; follow-up vaccinations every 3–4 weeks 
until 16 weeks of age.
• Vaccination will not prevent virus infection 
in subsequent exposure, but can prevent 
serious clinical disease caused by most strains; 
FCV–VSD can occur in vaccinated cats.
• Environmental management—decrease 
housing density; isolate affected cats by >4 ft; 
beware of hygiene and fomites; disinfect with 
dilute (1 : 30) bleach.
• Interstitial pneumonia—most serious 
complication; can be life-threatening.
• Secondary bacterial infections of lungs or 
upper airways.
• Clinical disease—usually appears 3–4 days 
after exposure.
• With supportive care, infection usually 
self-limiting and cats with upper respiratory 
signs respond favorably within 7–10 days.
• Oral ulcerations typically improve in 2–3 
weeks.
• Lameness usually resolves in 1–2 days.
• Prognosis excellent, unless severe pneumonia 
or systemic hemorrhagic disease develops.
• FCV–VSD may be severe and fatal.
• Recovered cats—persistently infected for 
long periods; will shed small quantities of 
virus in oral secretions continuously.
Affected cats may also be concurrently infected 
with FHV-1, especially in multicat and breeding 
facilities. FCV has been implicated in develop -
ment of feline chronic gingivostomatitis.
Usually occurs in young kittens whose 
maternally derived immunity has waned.
None
Generally no problem, because most cats have 
been exposed or vaccinated before becoming 
pregnant.
SYNONYMS
• Feline picornavirus infection—FCV 
originally classified as a picornavirus; older 
literature refers to the infection by this name; 
no known picornavirus infects cats.• Limping kitten syndrome.
• Hemorrhagic calicivirus.
SEE ALSO
• Chlamydiosis—Cats.
• Rhinitis and Sinusitis.
• Stomatitis and Oral Ulceration.
• FCV–VSD = feline calicivirus–virulent 
feline-calicivirus-infection-2012-edition
Afonso MM, Gaskell RM, Radford A. Feline 
upper respiratory infections. In: Ettinger SJ, 
Feldman EC, Côté, E, eds. Textbook of 
the Dog and Cat, 8th ed. St. Louis, MO: 
Elsevier, 2017, pp. 1013–1016.
Gaskell RM, Dawson S, Radford AD. Feline 
respiratory disease. In: Greene CE, ed., 
Infectious Diseases of the Dog and Cat, 4th 
ed. St. Louis, MO: Saunders Elsevier, 2012, 
pp. 151–162.
Pedersen NC, Elliot JB, Glasgow A, et al. An 
isolated epizootic of hemorrhagic-like fever 
in cats caused by a novel and highly virulent 
strain of feline calicivirus. Vet Microbiol 
2000, 73:281–300.
available onlineFeline Calicivirus Infection  (continued)

Canine and Feline, Seventh Edition  501
FFeline Herpesvirus Infection
  BASICS
An acute disease in cats characterized by 
sneezing, fever, rhinitis, conjunctivitis, and 
ulcerative keratitis.
Feline herpesvirus-1 (FHV-1) causes acute 
cytolytic infection of respiratory or ocular 
epithelium after oral, intranasal, or conjunctival 
exposure. The intracellular virus travels from 
cell to cell and does not stimulate a strong 
immune response from the host.
• Integumentary—herpes dermatitis near the 
nares.
• Ophthalmic—conjunctivitis with serous or 
purulent ocular discharge; ulcerative keratitis 
or panophthalmitis.
• Reproductive—in utero infection (infected 
pregnant queen) may result in severe neonatal 
herpetic infection.
• Respiratory—rhinitis with sneezing and 
serous to purulent nasal discharge; chronic 
sinusitis may result; tracheitis possible.
• Neurologic—latent virus found in optic 
nerve, ciliary ganglion, brainstem, cerebellum, 
and olfactory bulb.
GENETICS
N/A
• Common, especially in multicat households 
or facilities housing large numbers of cats; 
catteries and shelters are source of most 
• Perpetuated by latent carriers that harbor 
virus in nerve (especially trigeminal) ganglia.
Worldwide
Species
All domestic and many exotic cats.
• None.
• Brachycephalic breeds have more severe 
corneal disease and are more likely to have 
corneal sequestra.
• All ages.
• Kittens most susceptible.
N/A
SIGNS
• Acute onset of paroxysmal sneezing.
• Blepharospasm and ocular discharge.
• Anorexia (from high fever, general malaise, 
or inability to smell).• Recurrent signs—carriers.
• Abortion.
• Fever—up to 106 °F (41 °C).
• Rhinitis—serous, mucopurulent, or 
purulent discharge.
• Conjunctivitis—serous, mucopurulent, or 
• Chronic rhinitis/sinusitis—chronic 
purulent nasal discharge.
• Keratitis—ulceration, descemetocele, 
CAUSES
FHV-1
• Lack of vaccination for FHV-1, although 
vaccines do not bestow sterilizing immunity.
• Multicat facilities with overcrowding, poor 
ventilation, poor sanitation, poor nutrition, 
or physical or psychologic stress.
• Pregnancy and lactation.
• Concomitant disease, especially owing to 
immunosuppressive organisms or other 
respiratory organisms.
• Kittens born to carrier queens—infected ~5 
  DIAGNOSIS
• Feline calicivirus infection—less sneezing 
than FHV-1, conjunctivitis, ulcerative 
keratitis; may cause ulcerative stomatitis, 
• Feline Chlamydophila  infection—more 
chronic conjunctivitis, which may be 
unilateral; pneumonitis; intracytoplasmic 
inclusions in conjunctival scrapings; 
responds to tetracyclines or 
chloramphenicol.
• Bacterial infection ( Bordetella , Haemophilus , 
or Pasteurella )—less nasal and ocular 
involvement; often respond to antibiotics.
• T ransient leukopenia followed by 
leukocytosis may occur.
• PCR testing from pharyngeal and 
conjunctival swabs will identify presence of 
virus; more sensitive than other diagnostic 
modalities; may be transiently positive 
following vaccination with modified live virus 
(MLV) vaccine for FHV-1.
• Immunofluorescent assay—nasal or 
conjunctival scrapings; viral detection.
• Viral isolation—pharyngeal swab 
sample.
• Stained conjunctival smears—detect 
intranuclear inclusion bodies.IMAGING
• Radiography—open-mouth ventrodorsal 
and rostrocaudal (skyline) views of skull 
reveal presence of chronic disease in nasal 
cavity and frontal sinuses; infection cannot be 
reliably distinguished from neoplasia and 
inflammatory polyps; no abnormal 
radiographic findings with acute disease.
• CT provides more accurate assessment of 
disease in nasal cavity and frontal sinus 
compared to radiographs; CT may 
differentiate neoplasia from inflammation 
based on amount of bony destruction.
N/A
• Gross—ocular and nasal discharge, 
mucosal edema of upper airway epithelium, 
tracheitis, sinusitis, ulcerative keratitis, 
• Microscopic—submucosal edema, 
inflammatory cell infiltrates of upper 
respiratory and conjunctival tissues, chronic 
sinusitis, intranuclear inclusion bodies in 
  TREATMENT
• Inpatient—nutritional and fluid support to 
anorectic cats.
• Outpatient—if eating and afebrile.
• Outpatient—keep patient indoors to 
prevent environmentally induced stress, 
which may lengthen disease course.
• Fluids—IV or SC; to correct and prevent 
dehydration; to keep nasal secretions thin.
• Appetite stimulant as needed 
(mirtazapine—1.8 mg/cat PO q24–48h).
ACTIVITY
Isolate affected cats during acute phase 
because they are contagious.
DIET
• Outpatient—encourage food consumption 
to avoid anorexia; offer foods with appealing 
tastes and smells; warming food may enhance 
smell.
• Inpatient—forced enteral feeding for 
anorectic cats; remove nasal secretions (so 
nasal breathing can occur) before starting 
orogastric or esophagostomy tube feeding; 
avoid nasoesophageal tubes because of 
rhinitis.
• Inform client of contagious nature of 
disease.
• Discuss proper vaccination protocols and 
early vaccination of cats in multicat facilities 
and households.

502  Blackwell’s Five-Minute Veterinary Consult  
F• Inform client that early weaning and 
isolation from all other cats except littermates 
may prevent infections.
Surgically implanted feeding tubes (esopha -
gostomy tube, gastrostomy tube) may be 
needed to manage prolonged anorexia.
• Antibiotics not recommended if nasal 
discharge is serous and lacks purulent or 
mucopurulent component; antibiotics 
recommended only if fever, lethargy, or 
anorexia present concurrently with 
mucopurulent nasal discharge.
• Doxycycline (10 mg/kg PO q24h) 
recommended; amoxicillin (22 mg/kg PO/
IM/SC q8–12h) or ampicillin (10–20 mg/kg 
IV/IM/SC q6–8h) for secondary bacterial 
• Famciclovir (40–90 mg/kg PO 12h) may 
shorten course and severity of disease.
• Ophthalmic antibiotics—for keratitis.
• Ophthalmic antivirals for herpetic ulcers in 
order of efficacy—trifluridine, cidofovir, 
idoxuridine, ganciclovir, aciclovir; must be 
instilled q2h for significant effect, except for 
cidofovir which can be given q12h, making it 
ophthalmic drug of choice, although it must 
be compounded.
• Some evidence that administration of 
intranasal vaccine 2–6 days prior to exposure 
will result in lessening of clinical signs; may 
be helpful in outbreak in multicat setting.
• Idoxuridine ophthalmic—may be painful; 
discontinue medication.
• Cidofovir ophthalmic—scarring of 
nasolacrimal duct reported in humans, 
rabbits.
• T rifluridine, idoxuridine, acyclovir—toxic if 
given systemically.
• Systemic corticosteroids—may induce 
relapse in chronically infected cats.
• Ophthalmic corticosteroids—may 
predispose to ulcerative keratitis
• Nasal decongestant drops—0.25% 
oxymetazoline HCl; decrease nasal discharge; 
contraindicated because some cats object and 
some experience rebound rhinorrhea.
• Oral doxycycline tablets can cause 
esophageal ulceration.
• Death usually result of inadequate 
nutritional and fluid support or immuno -
suppression due to feline leukemia virus (FeLV) or feline immunodeficiency virus 
(FIV).
• Lysine (500 mg PO q12h) might reduce 
viral shedding, clinical signs.
• Lysine-lactoferrin (500 mg PO q12h) 
more effective than lysine alone for 
• Penciclovir—effectively inhibits FHV-1, 
doses unknown at this time.
  FOLLOW-UP
Monitor appetite closely; hospitalize for fluids 
and tube feeding if anorexia develops.
Can survive in environment for several hours; 
drying and most disinfectants effectively kill 
the virus.
Vaccines
• Routine vaccination with MLV or 
inactivated virus vaccine—prevents 
development of severe disease; does not 
prevent infection and local viral replication 
with mild clinical disease and virus 
shedding.
• Vaccinate at 8–10 weeks, 12–14 weeks, and 
16–18 weeks of age and with annual boosters 
for reasonable protection, especially in 
high-risk populations.
• Endemic multicat facilities or households—
vaccinate kittens with dose of intranasal 
vaccine at 10–14 days of age, then 
parenterally at 6, 10, and 14 weeks of age; 
isolate litter from all other cats at 3–5 weeks 
of age; then use kitten vaccination protocol to 
prevent early infections.
• Chronic rhinitis or rhinosinusitis with 
long-term sneezing and nasal discharge.
• Herpetic ulcerative keratitis.
• Corneal sequestrum that must be removed 
• Permanent closure of nasolacrimal duct 
with chronic ocular discharge.
• 7–10 days followed by spontaneous 
remission, if secondary bacterial infections do 
not occur.
• Prognosis generally good, if fluid and 
nutritional therapy are adequate.
• Correlation between severity of acute signs 
and degree of latent infection.
• May become chronically affected and 
exhibit respiratory signs long term.  MISCELLANEOUS
Simultaneous viral or bacterial respiratory diseases.
More severe in young kittens.
None
Pregnant cats with FHV infection may 
transmit FHV-1 to kittens in utero, resulting 
in abortion or neonatal disease.
SYNONYMS
• Coryza.
• Feline rhinotracheitis.
• Rhino.
SEE ALSO
Feline Calicivirus Infection.
Bol S, Bunnik EM. Lysine supplementation is 
not effective for the prevention or treatment of 
feline herpesvirus 1 infection in cats: a 
systematic review. BMC Vet Res 2015, 11:284.
Horzinek MC, Addie D, Sándor B, et al. ABCD: 
update of the 2009 guidelines on prevention 
and management of feline infectious diseases. J 
Feline Med Surg 2013, 15:530–539.
Lappin MR, Blondeau J, Boothe D, et al. 
Antimicrobial use guidelines for treatment 
of respiratory tract disease in dogs and cats. 
J Vet Intern Med 2017, 31:279–294.
Malik R, Lessels NS, Webb S, et al. T reatment 
of feline herpesvirus-1 associated disease. 
J Feline Med Surg 2009, 11(1):40–48.
Thiry E, Addie D, Belak S, et al. Feline 
herpesvirus infection: ABCD guidelines on 
prevention and management. J Feline Med 
Surg 2009, 11(7):547–555.
Thomasy SM, Maggs DJ. A review of 
antiviral drugs and other compounds with 
activity against feline herpesvirus-1. Vet 
Ophthalmol 2016, 19(Suppl 1):119–130.
Author  Lisa Restine
Gary D. Norsworthy.
available onlineFeline Herpesvirus Infection  (continued)

Canine and Feline, Seventh Edition  503
FFeline Hyperesthesia Syndrome
  BASICS
OVERVIEW
• Idiopathic disorder of cats characterized by 
paroxysmal agitation, focal epaxial muscle 
spasms, vocalization, and intense biting or 
licking of the back, tail, and pelvic limbs.  
• Also known as atypical neurodermatitis, rolling 
skin disease, apparent neuritis, and twitchy cat 
disease. •  Pathophysiology unknown.  
• Organ systems affected—behavioral, nervous, 
neuromuscular, skin/exocrine.
Species
Cat
Can be seen in any breed; Siamese, 
Abyssinian, Burmese, and Himalayan may be 
Most common at 1–7 years of age.
SIGNS
• Episodes of twitching of skin over lumbar area, 
violent swishing of tail, vocalizing, and biting or 
licking of flank, pelvic region, or tail. •  Pupils 
often dilate, and cats can become aggressive or 
appear agitated and run wildly about the 
environment. •  Episodes are several seconds to 
several minutes in length; cats are typically normal 
between episodes, but may be intolerant of being 
stroked along the back. •  General physical 
examination often reveals no abnormalities aside 
from possible alopecia and broken hair over 
lumbar area from self-mutilation; many cats resent 
palpation of thoracolumbar musculature, and 
manipulation of area may elicit an episode; no 
neurologic deficits present.
• Not known whether this syndrome is 
manifestation of underlying behavioral 
problem, dermatopathy, focal seizure disorder, 
or abnormal sensory state causing neuropathic 
pain or itch; speculated that cause is 
multifactorial, or that syndrome is not 
distinct entity with single cause, but rather 
can develop from variety of different factors. 
• Cats that tend to be nervous or 
hyperexcitable may be at increased risk; 
environmental stressors can serve as trigger.
  DIAGNOSIS
• Dermatologic conditions causing pruritus—
parasitic (e.g., flea, Notoedres , Cheyletiella ), 
fungal (e.g., dermatophytosis), or allergic (e.g., 
parasitic, inhalant, dietary); evaluate for 
underlying dermatitis; skin scrapings and fungal 
cultures can help confirm diagnosis. •  Diseases of spinal cord, nerve roots, epaxial muscles, or 
vertebral column causing pain—degenerative 
(intervertebral disc disease), inflammatory 
(discospondylitis, meningitis, myositis), 
neoplastic, or traumatic; spinal radiographs 
helpful in evaluating for abnormalities; further 
diagnostics (e.g., advanced imaging, serology for 
infectious agents, cerebrospinal fluid [CSF] 
analysis) may be necessary. •  Forebrain disease 
causing behavioral changes and/or seizures—
metabolic (hepatic encephalopathy), infectious/
inflammatory (feline leukemia virus, feline 
immunodeficiency virus, feline infectious 
peritonitis, cryptococcosis, toxoplasmosis), 
neoplastic, vascular; complete diagnostic 
evaluation including bile acid tolerance, testing 
for infectious causes, CSF analysis, and brain 
imaging may be indicated. •  Behavioral 
condition—compulsive disorder; exclusion 
Frequently normal.
IMAGING
None required aside from that necessary to 
exclude differential diagnoses.
• Diagnosis based on characteristic history 
and clinical findings, and by excluding other 
diseases that can cause similar signs. •  No test 
or group of tests support definitive diagnosis. 
• Electromyography (EMG)—evidence of 
abnormal spontaneous activity in thora -
columbar epaxial muscles in one study of 
affected cats. •  Muscle biopsy—if EMG 
changes; isolated report of vacuoles within 
epaxial muscles, with antibody labeling 
characteristics similar to those described with 
inclusion body myositis/myopathy in humans.
  TREATMENT
• Outpatient. •  Eliminate environmental 
changes that can precipitate episodes. 
• Behavioral modification has been successful 
in reducing clinical manifestations in some 
cats. •  In severe cases of self-mutilation, 
Elizabethan collar or tail bandaging may be 
• Several pharmacologic agents recommended, 
based on suspected underlying cause. 
• Prednisolone indicated if pruritic dermatitis 
suspected. •  Antiepileptic drugs often utilized; 
phenobarbital (1–2 mg/kg PO q12h) effective 
in some cats; gabapentin (5–10 mg/kg PO 
q12h) can be used for both anti  epileptic and 
analgesic properties; topiramate (5 mg/kg PO 
q12h) is antiepileptic that has also been used to treat self-mutilation in cats. •  Selective 
serotonin reuptake inhibitors (fluoxetine 
0.5–2.0 mg/kg PO q24h), tricyclic 
antidepressants (clomipramine 0.5–1.0 mg/kg 
PO q24h), or benzodiazepines (lorazepam 
0.125–0.50 mg per cat PO q8–24h) 
recommended when primary behavioral disorder 
suspected. •  Combination therapy often 
required. •  T reatment response variable; in cats 
that respond, therapy often lifelong as episodes 
tend to resume after medication discontinued.
Fluoxetine inhibits the cytochrome P450 
system and should be used cautiously with 
other drugs that undergo extensive hepatic 
metabolism, including phenobarbital, 
benzodiazepines, and tricyclic antidepressants.
  FOLLOW-UP
Cats administered phenobarbital—check 
serum drug concentrations in 2–3 weeks and 
adjust dosage as needed to maintain levels of 
20–30  μg/mL (85–130  μmol/L); CBC and 
biochemistry profile at 6–12-month intervals 
to monitor for adverse effects.
Prognosis depends on whether underlying 
cause is identified, response to medication, 
and frequency and severity of episodes.
Amengual Batle P , Rusbridge C, Nuttall T, 
et al. Feline hyperaesthesia syndrome with 
self-trauma to the tail: retrospective study of 
seven cases and proposal for integrated 
multidisciplinary diagnostic approach. J 
Feline Med Surg 2019, 21(2):178–185. doi: 
10.1177/1098612X18764246
Author  Karen R. Muñana

F504  Blackwell’s Five-Minute Veterinary Consult  
FFeline Idiopathic Lower Urinary Tract Disease
  BASICS
Idiopathic lower urinary tract disease, 
commonly referred to as feline idiopathic cystitis 
(FIC), is a nonmalignant, sterile, inflammatory 
disease of the urinary bladder and urethra. It is 
the most common urinary disorder of young to 
middle-aged cats and is characterized by dysuria, 
pollakiuria, hematuria, periuria, and in some 
cases urinary obstruction. Clinical observations 
suggest that FIC is associated with different 
clinical phenotypes (acute self-limiting, 
chronic, nonobstructive, and obstructive 
forms) and pathologic phenotypes (ulcerative, 
inflammatory, hyperplastic, nonulcerative, and 
noninflammatory forms). Regardless of form, 
the terms idiopathic lower urinary tract disease 
and FIC represent an exclusionary diagnosis 
established only after known causes have been 
eliminated.
• Etiopathogenesis is uncertain.
• Urinary bladder abnormalities include 
alterations in urothelial barrier structure and 
function, differentiation and repair, signaling, 
eicosanoid biosynthesis, and innate immune 
and inflammatory responses.
• Association of FIC with stress (environ -
mental, psychologic, physiologic, or comorbid 
pathologic stressors) and identification of 
multiple abnormalities of nervous and 
endocrine systems have led to hypothesis that 
systemic psychoneuroendocrine factors may 
have a role in the pathogenesis.
• Clinical and morphologic features of 
chronic forms of FIC are similar to those of 
an idiopathic cystopathy of humans called 
interstitial cystitis/painful bladder syndrome 
(IC/PBS). However, the extent to which the 
feline and human forms share pathogenic 
mechanisms has not yet been fully defined.
• Renal/urologic—lower urinary tract.
• Persistent urethral outflow obstruction 
results in postrenal azotemia.
• Incidence of hematuria, dysuria, and/or 
urethral obstruction (UO) in domestic cats has 
been previously reported to be ~0.5–1% per year.
• Hospital morbidity rate for FIC in cats 
with lower urinary tract signs is ~65%; it is 
the single most common cause of lower 
urinary tract signs in cats.
Species
Cat
• May occur at any age, but most commonly 
recognized in young to middle-aged adults 
(mean 3.5 years, range: 2–7 years).• Uncommon in cats <1 and >10 years old.
SIGNS
• Dysuria.
• Pollakiuria.
• Periuria.
• Urge incontinence.
• Outflow obstruction.
Thickened, firm, contracted bladder wall.
CAUSES
• Male, middle-aged, and overweight cats, 
as well as cats housed indoors or living in 
a home with other cats, are at increased 
risk.
• Feeding dry food has not been consistently 
recognized as a risk factor.
• Stress may play a role in precipitating or 
exacerbating signs.
  DIAGNOSIS
• Metabolic disorders including various types 
of uroliths/urethral plugs.
• Urinary tract infection (UTI) from bacteria, 
mycoplasma/ureaplasma, fungal agents, and 
• T rauma.
• Neurogenic disorders including reflex 
dyssynergia, urethral spasm, and hypotonic or 
atonic bladder.
• Iatrogenic disease including reverse 
flushing solutions, indwelling and 
postsurgical urethral catheters, and 
urethrostomy complications.
• Anatomic abnormalities including urachal 
anomalies and acquired urethral strictures.
• Clinical signs may be confused with 
constipation.
• Hematuria and proteinuria without 
significant pyuria or bacteriuria—usually 
present.
• If UO persists, serum chemistry profiles 
reveal azotemia, hyperphosphatemia, 
hyperkalemia, and acidosis.
• Absence of bacteriuria—verify by quantitative 
urine culture; collect urine specimens by 
cystocentesis to avoid contamination.
• T ransmission electron microscopy has revealed 
calicivirus-like particles in some urethral plugs.
IMAGING
• Survey radiography may exclude radiopaque 
uroliths or urethral plugs.• Ultrasonography may exclude uroliths and 
thickening of bladder wall due to inflammation 
or neoplasia.
• Contrast cystography may exclude small or 
radiolucent uroliths, blood clots, urethral 
stricture, vesicourachal diverticula, and 
thickening of bladder wall due to 
inflammation or neoplasia.
• Cystoscopy may exclude uroliths and 
• Biopsies of urinary bladder wall may permit 
morphologic characterization of inflammatory 
or neoplastic lesions.
• Cystoscopy may reveal petechial 
hemorrhages (glomerulations) of urinary 
bladder mucosa.
• Mucosal ulceration or hyperplasia, submucosal 
edema, hemorrhage, neovasculari  zation, fibrosis, 
and mononuclear inflammatory cell infiltrates 
are prominent features of chronic FIC.
  TREATMENT
tract diseases—typically managed as outpatients; 
• Patients with obstructive lower urinary tract 
diseases—usually hospitalized for diagnosis 
and management.
DIET
• Results of prospective, randomized, double-
masked, controlled clinical trial provided 
evidence that feeding specific multipurpose 
therapeutic urinary food (Hill’s c/d Multicare) 
enriched with omega-3 fatty acids (EPA and 
DHA) and antioxidants significantly reduced 
rate of recurrent episodes of FIC signs.
• Low-grade evidence that recurrence of signs 
may be minimized by feeding moist foods.
• Appropriate dietary management for 
persistent crystalluria associated with matrix-
crystalline urethral plugs.
• Hematuria, dysuria, and pollakiuria—often 
self-limiting within 4–7 days in most cats. 
Signs may recur unpredictably; up to 65% of 
cats experience ≥1 episodes within 1–2 years.
• A lack of controlled studies demonstrating 
efficacy of most drugs used to treat this 
disorder symptomatically.
• Reduce environmental stress by minimizing 
impact of changes in the home and 
maintaining a constant diet. Environmental 
enrichment for indoor-housed cats consists of 
provision of necessary resources (food, water, 
litter boxes, space, play), providing a safe 
place to hide, refinement of cat–owner 
interactions, and management of conflict.

Canine and Feline, Seventh Edition  505
F
F• Provide proper litter box hygiene.
• Males should be monitored for signs of 
UO.
Do not perform perineal urethrostomy to 
minimize recurrent UO without localizing 
obstructive disease to penile urethra by 
contrast urethrography.
• Amitriptyline—empirically advocated to treat 
cats with severe recurrent or persistent signs; 
suggested dosage is 5–10 mg/cat q24h given at 
night; not recommended for treatment of 
acute, self-limiting episodes of FIC.
• Butorphanol, buprenorphine, and fentanyl—
have been empirically recommended for 
short-term analgesia in cats with FIC; there 
have been no reports of controlled studies to 
evaluate their safety or efficacy.
• Prazosin—may be used to minimize reflex 
dyssynergia and functional urethral outflow 
obstruction; suggested dosage is 0.25–0.5 mg/
cat PO q12–24h.
• Tolteridine may be considered as an 
anticholinergic and antispasmodic to minimize 
hyperactivity of bladder detrusor muscle and 
urge incontinence; suggested dose is 0.05 mg/
kg PO q12h; there have been no controlled 
studies to evaluate its safety or efficacy.
• Glycosaminoglycans—empirically recom -
mended to help repair glycosaminoglycan 
coating of urothelium; results of controlled 
clinical studies have not demonstrated any 
beneficial effects on reducing severity or 
frequency of clinical signs in cats with FIC.
• Feline facial pheromone—empirically 
recommended to decrease signs of stress in 
cats with FIC; results of controlled clinical 
studies have not demonstrated any beneficial 
effects in management of FIC.
• Corticosteroids—no detectable effect on 
remission of acute clinical signs demonstrated; 
predispose to bacterial UTIs, especially in cats 
with indwelling transurethral catheters.
(NSAIDs)—empirically recommended by some because of their anti-inflammatory and 
analgesic properties; the safety of NSAIDs in 
the treatment of FIC has not been evaluated 
by controlled clinical trials.
• Antibiotics—no detectable effect on 
remission of clinical signs in cats demonstrated.
• Phenazopyridine—may result in methemo -
globinemia and irreversible oxidative changes 
in hemoglobin resulting in formation of 
Heinz bodies and anemia.
• Methylene blue—may cause Heinz bodies 
and severe anemia.
• Bethanechol—do not use in patients with 
UO.
• Cats with UO and postrenal azotemia are at 
increased risk for adverse drug events, 
especially with drugs and anesthetics that 
depend on renal elimination or metabolism.
• Indwelling transurethral catheters, 
especially when associated with fluid-
induced diuresis, predispose patients to 
bacterial UTIs.
  FOLLOW-UP
Monitor hematuria by urinalysis; 
cystocentesis may cause iatrogenic hematuria, 
so naturally voided samples are preferred.
Best evidence suggests that multimodal 
approach to managing cats with acute 
nonobstructive FIC is advised, including 
multipurpose therapeutic urinary food proven 
to reduce rate of recurrent episodes of FIC 
signs (Hill’s c/d Multicare); environmental 
enrichment; feeding moist food; and short-
term administration of analgesics to control 
signs of pain.
• Indwelling transurethral catheters—cause 
trauma; predispose to ascending bacterial 
UTIs.
• Perineal urethrostomies—predispose to 
bacterial UTIs and urethral strictures.EXPECTED COURSE AND PROGNOSIS
Hematuria, dysuria, and pollakiuria often 
self-limiting within 4–7 days in most 
patients. These signs often recur 
unpredictably.
Frequency of recurrence appears to decline 
with advancing age.
SYNONYMS
• Feline idiopathic cystitis.
• Feline interstitial cystitis.
SEE ALSO
• Dysuria, Pollakiuria, and Stranguria.
• FIC = feline idiopathic cystitis.
• IC/PBS = interstitial cystitis/painful bladder 
syndrome.
drug.
• UO = urethral obstruction.
Forrester SD, Towell TL. Feline idiopathic 
cystitis. Vet Clin Small Anim 2015, 
45:783–806.
Kruger JM, Lulich JP , MacLeay J, et al. A 
randomized, double-masked, multicenter, 
clinical trial of two foods for long-term 
management of acute nonobstructive feline 
idiopathic cystitis (FIC). J Am Vet Med 
Assoc 2015; 247:508–517.
of Carl A. Osborne and Jody P . Lulich
available online(continued)  Feline Idiopathic Lower Urinary Tract Disease

506  Blackwell’s Five-Minute Veterinary Consult  
FFeline Immunodeficiency Virus (FIV) Infection
  BASICS
A complex retrovirus that causes 
immunodeficiency in domestic cats; same 
genus ( Lentivirus ) as human immuno­
deficiency virus (HIV).
• Infection causes immune dysfunction due 
to cytokine alterations, nonspecific hyper­
activation of B and T lymphocytes, and 
apoptosis of T cells.
• Strain or subtype influences pathogenicity; 
subtypes A and B are most common in the 
• Acute infection—virus spreads from site of 
entry to lymph tissues and thymus via 
dendritic cells, first infecting T lymphocytes, 
then macrophages.
• Primary receptor is feline CD134; uses 
chemokine receptor CXCR4 as co ­receptor.
• CD4+ and CD8+ T cells can be infected; 
virus selectively and progressively decreases 
CD4+ (T ­helper) cells; inversion of the 
CD4+ : CD8+ ratio (from ∼2 : 1 to <1 : 1) 
develops slowly, with absolute decrease of 
CD4+ T cells after several months of infection.
• Early infection and activation of CD4+ 
CD25+ regulatory T cells may limit effective 
immune response to FIV infection.
• Cats clinically asymptomatic until cell ­ 
mediated immunity is disrupted; humoral 
immune function declines in advanced stages 
of infection.
• T cells and macrophages—main cellular 
reservoirs of virus in affected cats; lymphoid 
tissues are reservoirs throughout the body.
• Astrocyte and microglial cells in brain and 
megakaryocytes and mononuclear bone 
marrow cells may be infected; neuronal loss 
may occur.
• Co­infection with feline leukemia virus 
(FeLV) may increase expression of FIV in 
many tissues, including kidney, brain, and 
liver.
• Hemic/lymphatic/immune—loss of CD4+ 
T cells; lymphocytic/plasmocytic infiltrates in 
tissues (especially gingiva, lymphoid tissues); 
lymphomas, mast cell tumors.
• Gastrointestinal—panleukopenia ­like 
syndrome.
• Nervous—alterations in astrocyte function 
and neurotransmitter expression.
• Ophthalmic—anterior uveitis.
• Renal/urologic—nephropathy.
• Reproductive—fetal death or perinatal 
• Cardiovascular—possible myocarditis.
• Other body systems—secondary infections.GENETICS
No predisposition for infection, but may play 
role in progression and severity.
United States and Canada—1–3% prevalence 
in healthy cat populations; 9–15% in sick 
cats.
Worldwide; variable seroprevalence.
Species
Cat
• Prevalence of infection increases with age.
• Mean age—6 years at time of diagnosis.
Male—more aggressive; roaming.
SIGNS
• Diverse due to immunosuppressive nature.
• Cannot be clinically distinguished from 
FeLV ­associated immunodeficiency.
Recurrent minor illnesses, especially upper 
respiratory and gastrointestinal.
• Opportunistic infections.
• Lymphadenomegaly—mild to moderate.
• Gingivitis, stomatitis, periodontitis 
(25–50% of cases).
• Rhinitis, conjunctivitis, keratitis (30% of 
cases); often associated with feline herpesvirus 
and calicivirus infections.
• Persistent diarrhea (10–20% of cases); 
bacterial or fungal overgrowth, parasite ­
induced inflammation; direct effect of FIV on 
gastrointestinal epithelium.
• Chronic, nonresponsive, or recurrent 
infections of external ear and skin—bacterial 
infections or dermatophytosis.
• Fever and wasting—especially in later 
stage.
• Ocular disease—anterior uveitis; pars 
planitis; glaucoma.
• Neurologic abnormalities—disruption of 
normal sleep patterns; behavioral changes 
(pacing and aggression); motor and 
neurocognitive deficits; peripheral 
neuropathies.
CAUSES
• Cat­to­cat transmission—usually by bite 
wounds.
• Occasional perinatal transmission.
• Sexual transmission uncommon, although 
FIV has been detected in semen.
• Male.
• Free­roaming or feral.  DIAGNOSIS
• Primary bacterial, parasitic, fungal, or viral 
infections, especially FeLV.
• Toxoplasmosis—neurologic and ocular 
manifestations may be the result of 
Toxoplasma  infection, FIV infection, or both.
• Nonviral neoplastic diseases.
• Chronic kidney disease.
• Anemia, lymphopenia, or neutropenia—
common; but neutrophilia may occur in 
response to secondary infections; may also be 
normal.
• Urinalysis and serum chemistry profile—
hypergammaglobulinemia, azotemia with 
isosthenuria, proteinuria (immune ­mediated 
glomerulonephritis).
• Detects antibodies to FIV.
• ELISA—routine screening; point ­of­care 
and diagnostic laboratory kits; confirm 
positive results with additional testing, 
especially in healthy, low ­risk cats.
• Western blot (immunoblot)—confirmatory 
testing of ELISA ­positive samples.
• Kittens—when <6 months old may test 
positive owing to passive transfer of anti­
bodies from FIV ­positive queen; positive test 
does not indicate infection; retest at 8–12 
months to determine infection.
• Vaccinated cats may test positive for FIV 
Others
• Virus isolation and subtyping.
reaction (RT ­PCR)—useful in vaccinated cats 
or kittens with maternal antibody.
• CD4+ : CD8+ evaluation—helps 
determine extent of immunosuppression.
IMAGING
N/A
N/A
• Lymphadenopathy—initially, follicular 
hyperplasia and paracortical infiltration of 
plasmacytes; later, follicular hyperplasia with 
follicular depletion or involution; in terminal 
stages, lymphoid depletion.
• Lymphocytic and plasmacytic infiltrates—
gingiva, lymph nodes and other lymphoid 
tissues, spleen, kidney, liver, and brain.
• Perivascular cuffing, gliosis, neuronal loss, 
white matter vacuolization, and occasional 
giant cells in the brain.

Canine and Feline, Seventh Edition  507
F• Intestinal lesions similar to those seen with 
feline parvovirus infection.
  TREATMENT
• Outpatient sufficient for most patients.
• Inpatient—with severe secondary infections 
until stable.
• Primary consideration—manage secondary 
and opportunistic infections.
• Supportive therapy—parenteral fluids and 
nutrition, as required.
ACTIVITY
Normal
DIET
Normal, may alter as necessary for cats with 
diarrhea, kidney disease.
• Inform client that infection is slowly 
progressive and healthy antibody ­positive cats 
may remain healthy for years.
• Advise client that cats with clinical signs 
will have recurrent or chronic health 
problems that require medical attention.
• Discuss importance of keeping cats indoors 
to protect them from exposure to secondary 
pathogens and to prevent spread of FIV.
• Oral treatment or surgery—dental cleaning, 
tooth extraction, gingival biopsy as needed; 
gingivitis and stomatitis may be refractory to 
• Biopsy or removal of neoplastic lesions.
• Zidovudine (Retrovir®) 5–10 mg/kg PO 
q12h—antiviral agent; most effective against 
acute infection; monitor for bone marrow 
toxicity.
• Immunomodulatory drugs—may alleviate 
some clinical signs:
◦ α­interferon (Roferon® ­A)—diluted in 
saline at 30 units/day PO for 7 days, every 
other week; may increase survival rates and 
improve clinical status.
◦ Feline omega ­interferon (Virbagen® 
Omega)—1 million units/kg/day SC q24h 
for 5 days at 3 intervals (d0–4, d14–18, 
d60–64); lower ­dose oral protocols may be 
• Antibacterial or antimycotic drugs—as 
indicated; prolonged therapy or high dosages 
may be required.• Corticosteroids or gold salts—judicious but 
aggressive use may help control immune ­
mediated inflammation.
• Topical corticosteroids—for anterior 
uveitis; long ­term response may be 
incomplete or poor; pars planitis often 
regresses spontaneously and may recur.
• Glaucoma—standard treatment.
• Vaccinate for respiratory and enteric pathogens 
based on individual risk assessment. Rabies 
vaccination according to regulatory guidelines.
• Griseofulvin—avoid or use with extreme 
caution in FIV ­positive cats; may induce 
severe neutropenia; neutropenia is reversible if 
drug is withdrawn early enough, but 
secondary infections can be life ­threatening.
Systemic corticosteroids—use with caution; 
may lead to further immunosuppression.
• Propionibacterium acnes  
(ImmunoRegulin®)—0.5 mL/cat IV once or 
twice weekly.
• Acemannan (Carrisyn®)—100 mg/cat PO 
q24h.
  FOLLOW-UP
Varies according to secondary infections and 
other manifestations of disease.
• Prevent contact with FIV ­positive cats.
• Quarantine and test incoming cats before 
introducing into multicat households.
• Vaccine no longer available in the U.S.
• Approx. 20% of cats die within 2 years of 
diagnosis or 4.5–6 years after estimated time 
of infection, but >50% remain asymptomatic.
• In late stages of disease (wasting and 
frequent or severe opportunistic infections), 
life expectancy ≤1 year.
• Overall survival time and quality of life for 
many FIV ­positive cats will be similar to 
uninfected cats.
• Secondary bacterial, viral, fungal, and 
parasitic disease.
• Lymphoid tumors.
• Immune ­mediated disease.AGE-RELATED FACTORS
Kittens (up to 4–6 months old) may test 
positive because of passive antibody transfer.
• None known.
• Potential transmission of secondary 
pathogens (e.g., Toxoplasma gondii ) to 
immunocompromised humans.
FIV­positive queens—reported abortions and 
stillbirths; transmission to kittens infrequent 
if queen is antibody ­positive before 
conception; rate of transmission may be 
subtype or strain ­dependent ( >90% for 
experimental infections with some strains).
SYNONYMS
Feline immunodeficiency syndrome.
SEE ALSO
• Feline Stomatitis—Feline Chronic 
Gingivostomatitis (FCGS).
• Gingival Enlargement/Hyperplasia.
https://catvets.com/public/PDFs/Practice 
Guidelines/RetrovirusGLS ­Summary.pdf
• HIV = human immunodeficiency virus.
• RT­PCR = reverse transcriptase polymerase 
Hartmann K, Wooding A, Bergmann M. 
Efficacy of antiviral drugs against feline 
immunodeficiency virus. Vet Sci 2015, 
2:456–476.
Levy JK, Crawford CP , T ucker SJ. 
Performance of 4 point ­of­care screening 
tests for feline leukemia and feline 
immunodeficiency virus. J Vet Intern Med 
2017, 31:521–526.
Little S, Levy J, Hartmann K, et al. 2020 
AAFP feline retrovirus testing and 
management guidelines. J Feline Med Surg 
2020, 22:5–30.
Sykes JE. Feline immunodeficiency virus 
infection. In: Sykes JE, ed., Canine and 
Feline Infectious Diseases. St. Louis, MO: 
Elsevier Saunders, 2014, pp. 209–223.
Author  Margaret C. Barr
available online(continued)  Feline Immunodeficiency Virus (FIV) Infection

F
508  Blackwell’s Five-Minute Veterinary Consult  
FFeline Infectious Diarrhea
  BASICS
• Diarrhea is defined as excess fecal water, 
increased quantity of fecal material, or 
increased frequency of bowel movements.
• Etiologies include viral, enteropathogenic 
bacterial, protozoal, fungal, or helminths; 
small bowel, large bowel, or mixed bowel 
diarrhea.
• Secondary systemic signs likely with 
infection by feline immunodeficiency virus 
(FIV), feline leukemia virus (FeLV), feline 
enteric coronavirus (FECV), feline parvovirus 
(FPV), histoplasmosis.
screening does not indicate causation; patient 
factors (clinical signs, age, environmental 
exposure) should be considered before 
• Some cats will have self-resolution; 
diagnostic testing may be appropriate for 
more severely affected animals or if clinical 
signs are persistent despite supportive care 
and having ruled out other causes of acute or 
chronic diarrhea; kittens with acute diarrhea 
should be screened for FPV.
• Diarrhea may result from decreased 
intestinal absorption or increased intestinal 
secretion caused by enterotoxins, osmotic 
forces, or epithelial damage.
• Immune response to infectious organisms 
can contribute to development of diarrhea; 
activated white blood cells release 
inflammatory mediators that stimulate 
secretion and damage intestinal epithelium.
• Gastrointestinal (GI).
GENETICS
Feline infectious peritonitis (FIP) more likely 
in purebred cats.
• 84% of cats from shelters had entero -
pathogens—no difference with or without 
diarrhea.
• FECV more common in cats with diarrhea.
• Prevalence of etiologies varies by region.
• Histoplasma more common in eastern 
United States, Latin America.
Species
Cat
Purebred cats have higher prevalence of FIP .Mean Age/Range
Young cats more likely to develop diarrhea 
from FECV, FPV, Cryptosporidium , helminths; 
FIP has bimodal distribution (young and old).
FIP more frequent in males.
SIGNS
Range from mild to severe.
• Acute or chronic, small or large bowel diarrhea.
• Possibly lethargy, vomiting, weakness, 
weight loss, hyporexia.
• Crowded environment.
• Poor body condition.
• Fluid/gas-filled intestinal loops.
• Signs of sepsis or systemic inflammatory 
response syndrome (SIRS) possible—
tachycardia, hypotension, hyper/hypothermia, 
tachypnea, pale mucous membranes.
• Abdominal masses or enlarged lymph nodes 
may be palpable (histoplasmosis, FIP).
• With systemic infections may note 
chorioretinitis, icterus, neurologic deficits.
CAUSES
• Viral—FECV, FPV, astrovirus, calicivirus, 
FIV, FeLV, torovirus-like agent.
• Bacterial— Campylobacter  spp., Clostridium 
perfringens  enterotoxin A, Clostridium difficile  
toxins, Salmonella  spp., Escherichia coli, 
Yersinia spp .
• Helminth— Toxocara  spp., Ancylostoma  
spp., Strongyloides  spp., Toxascaris leonine, 
Spirometra  spp., Trichuris vulpis .
• Protozoal— Giardia  spp., Tritrichomonas 
foetus, Toxoplasma gondii .
• Fungal— Histoplasma capsulatum .
• Pediatric, young adult cats more commonly 
affected, particularly with helminths, viral, 
and coccidial disease.
• Crowding, poor sanitation increase risk of 
  DIAGNOSIS
• Acute diarrhea—dietary indiscretion, 
foreign body, GI neoplasia; non-GI diseases: 
hyperthyroidism, iatrogenic, hepatotoxicity, 
renal disease, and other systemic diseases 
(frequently have hyporexia, vomiting, 
icterus).
(dietary responsive, antibiotic responsive, 
dysbiosis, or inflammatory bowel disease), primary GI neoplasia, pancreatic 
insufficiency, and hepatic or renal disease.
• Eosinophilia with intestinal parasitism or 
histoplasmosis.
• Leukopenia with FPV, sepsis from 
salmonellosis or translocation, bone marrow 
involvement with histoplasmosis or FeLV.
• Anemia and microcytosis suggest GI 
hemorrhage or iron deficiency, particularly 
with high worm burden.
• Elevated liver enzyme activities or creatine 
kinase with toxoplasmosis.
• Hyperglobulinemia, elevated total bilirubin 
with FIP .
• Hemoconcentration, prerenal azotemia, 
electrolyte derangements with dehydration.
• Panhypoproteinemia if protein-losing 
enteropathy or GI blood loss.
IMAGING
diarrhea.
nonpediatric patients with diarrhea 
• Thoracic radiographs may show pulmonary 
disease or enlarged lymph nodes with 
histoplasmosis or toxoplasmosis.
false negatives are possible as ova are 
intermittently shed; cats suspected to have 
intestinal parasitism should have multiple fecal 
flotations or be treated with anthelmintics.
• T ritrichomonas PCR using “colonic flush” 
• Histoplasma enzyme immunoassay (EIA)— 
urine.
• Toxoplasmosis immunofluorescence 
antibody test (IFA) for immunoglobulin (Ig) 
G and IgM, rising titer between acute and 
convalescent samples.
• FIV antibody, FeLV antigen ELISA.
• Infectious diarrhea PCR panels assess for 
range of infectious causes of diarrhea; caution 
should be used in interpretation; positive 
results do not necessarily indicate causation 
and false-negative results possible.
intestinal mucosa with multifocal 
hemorrhagic ulcerations, submucosal 
congestion or hemorrhage, intestinal wall 
thickening, lymphadenopathy.
eosinophilic, neutrophilic, pyogranulomatous, 
or lymphoplasmacytic enteritis with varying

Canine and Feline, Seventh Edition  509
F
Fdegrees of hemorrhage and necrosis, depending 
on etiology; may visualize causative agent.
  TREATMENT
• Mildly affected cats treated as outpatients.
• Moderate to severely affected cats may require 
IV fluids for dehydration/electrolyte management.
parenterally for hypoglycemia,
ACTIVITY
N/A
DIET
• Diets high in easily digestible protein, 
including adequate taurine.
anorexia >48 hours.
• For most infectious organisms, 
environmental decontamination prevents 
reinfection and transmission to other pets/
humans; isolation during hospitalization may 
be warranted depending on cause.
• Cats with identified infectious causes of 
diarrhea should be isolated from other cats 
until clinical signs resolve; Histoplasma  not 
directly transmitted from cat to other hosts.
intussusceptions.
• Many cases self-resolve with supportive care 
and time.
• Empiric therapy, pending diagnostics if 
clinical signs persist—probiotics (Visbiome® 
112.5 billion bacteria/cat/day), or 
metronidazole 10 mg/kg PO q12h, with 
fenbendazole 50 mg/kg PO q24h for 5 days.
• Anthelmintics—fenbendazole 50 mg/kg 
PO q24h for 5 days; pyrantel pamoate 10 g/
kg PO q24h for 3 days.
• Coccidiostatic—sulfadimethoxine 50–60 
mg/kg PO q24h for 5–10 days; ponazuril 50 
mg/kg PO once.
signs—erythromycin 10–15 mg/kg PO q8h; 
azithromycin 5–10 mg/kg PO q24h.
• Histoplasmosis—itraconazole 5–10 mg/kg 
PO q12–24h: do not use compounded 
formulations.• Toxoplasmosis—clindamycin 10–17 mg/kg 
PO/IM/IV q8–12h for 4 weeks.
• T richomoniasis—ronidazole 30 mg/kg PO 
q24h for 14 days.
• Patients with sepsis or leukopenia should be 
treated with broad-spectrum antibiotics.
• Cats with confirmed salmonella should not be 
treated with antibiotics unless systemically ill.
N/A
• Metronidazole dose should be reduced in 
animals with hepatic insufficiency.
• Clindamycin should be given with food or 
water to prevent development of esophageal 
strictures.
• Ronidazole can cause neurotoxicity and 
should be discontinued if clinical signs 
including anorexia develop.
Dependent on drug used; itraconazole has 
many interactions.
  FOLLOW-UP
anemia, leukopenia, or electrolyte 
derangements as appropriate.
treatment suggest alternative cause of diarrhea.
reinfection possible (e.g., giardiasis, 
• Monthly flea and heartworm preventative 
with combination anthelmintic therapy.
• Maintain clean facilities and quarantine ill 
patients.
• Do not allow nonimmunocompetent 
patients to contact other animals until 
determined to be low risk.
• Sepsis.
• Anemia.
• Dehydration, electrolyte, acid-base 
• Infectious agents that cause systemic illness 
likely have worse prognosis.  MISCELLANEOUS
N/A
Young animals more susceptible.
• Toxoplasmosis—human abortion.
migrans, most common in children.
larval migrans, most common in children.
Patients exhibiting clinical signs of illness 
should not be bred. If illness develops while 
pregnant, take caution regarding drug choice.
SEE ALSO
• Feline Infectious Peritonitis (FIP).
• Feline Panleukopenia.
• Histoplasmosis.
• Whipworms (T ricuriasis).
• EIA = enzyme immunoassay.
• FECV = feline enteric coronavirus.
• FPV = feline parvovirus.
• IFA = immunofluorescence antibody test.
syndrome.
Green CE. Infectious Diseases of the Dog and 
Cat, 4th ed. St. Louis, MO: Elsevier 
Saunders, 2012.
Little SE. The Cat: Clinical Medicine and 
Management. St. Louis, MO: Elsevier 
Author  Genna Atiee
Consulting Editor  Amie Koenig(continued)  Feline Infectious Diarrhea

F
510  Blackwell’s Five-Minute Veterinary Consult  
FFeline Infectious Peritonitis (FIP)
  BASICS
A systemic, immune-mediated, viral disease 
of cats characterized by insidious onset, 
persistent fever, pyogranulomatous tissue 
reaction, exudative effusions in body cavities, 
and high mortality.
• The term feline coronavirus (FCoV) 
encompasses feline enteric coronavirus 
(FECV) and feline infectious peritonitis virus 
(FIPV).
• FECV is common and highly infectious; 
replicates locally in intestinal tract.
• FIPV infects monocytes/macrophages, 
which disseminate virus throughout body; 
localizes at vein wall and perivascular sites.
• FIP is an immune-mediated disease—
perivascular accumulation of virus-infected 
macrophages and inflammatory cells produces 
pyogranulomatous inflammation in various 
organs.
• Multisystemic—pyogranulomatous or 
granulomatous lesions on omentum, serosal 
surface of abdominal organs, within 
abdominal lymph nodes, and submucosa of 
intestinal tract.
• Nervous—vascular lesions throughout 
CNS, especially in meninges.
• Ophthalmic—uveitis, chorioretinitis, and 
iritis.
• Respiratory—lesions on lung surfaces, 
• Prevalence of antibodies against FCoV—
high, due to widespread presence of FECV, 
• Incidence of FIP—low in most populations, 
especially in single-cat households.
• Because of difficulty in diagnosis, control, 
and prevention, outbreaks within breeding 
catteries may be catastrophic; in endemic 
catteries, risk of FCoV antibody–positive cat 
eventually developing FIP is usually <10%.
Worldwide
Species
Cats—domestic and exotic.
Some bloodlines or breeds of cats may be 
more susceptible.
Highest incidence in kittens 3 months–2 
years of age.SIGNS
• Variable, depending on effectiveness of 
cell-mediated immune response, and organ 
system(s) affected.
• T wo classic forms—wet (effusive) and dry 
(noneffusive); depends on presence of 
effusion in body cavities; dry form may 
become wet form with disease progression.
• Insidious onset.
• Gradual weight loss and inappetence.
• Stunted growth in kittens.
• Gradual increase in size of abdomen due to 
effusion.
• Persistent fever—fluctuating, antibiotic 
• Fever.
• Poor condition.
• Dull, rough hair coat.
• Icterus.
• Abdominal and/or pleural effusion.
• Palpable abdominal masses (granulomas or 
pyogranulomas).
• Ocular—anterior uveitis, keratic precipitates, 
iris color change, irregularly shaped pupil.
• Neurologic—seizure, ataxia, paresis/
paralysis, abnormal behavior, cranial nerve 
deficits.
CAUSES
• Prevailing theory is that FECV mutates to 
FIPV during FECV infection in individual 
cats; weak cell-mediated immunity plays a 
role in development of FIP .
• FCoV has two genomic types (FCoV type 1 
and 2) and two biotypes (FECV and FIPV).
• FCoV type 1 is predominant (>85%); both 
types 1 and 2 can cause FIP .
• FECV—enteritis; highly transmissible 
among cats.
• FIPV—systemic, fatal disease (FIP); 
cat-to-cat transmission unlikely.
• Contact with FECV-shedding cat; >30% of 
cats are chronic shedders.
• Breeding catteries or multicat facilities.
• Less than 2 years of age.
• Feline leukemia virus (FeLV) or feline 
immunodeficiency virus (FIV) infection.
• Certain cat breeds have higher incidence of 
FIP , especially dry form; some breeding pairs 
are prone to producing litters that develop FIP .
 DIAGNOSIS
• Wet form—straightforward clinical diagnosis.
• Dry form—difficult to diagnose.• Reverse-transcription polymerase chain 
reaction (RT-PCR) or immunohistochemistry 
on effusion or affected tissue confirmatory.
• No single diagnostic laboratory test.
• Fever of unknown origin—infection, 
• Pleural effusion—cardiac disease; cardiac 
effusion has low specific gravity and cell 
count.
• Neoplasia—lymphoma, other causing 
abdominal organ enlargement/effusion.
• CNS signs—neoplasia, toxoplasmosis.
• Anemia and icterus—blood parasites 
causing hemolysis.
• Pansteatitis (yellow fat disease)—classic feel 
and appearance of fat within abdominal 
cavity; pain on abdominal palpation; often a 
fish-only diet.
• Leukopenia, enteritis—panleukopenia (see 
Feline Panleukopenia).
• Leukocytosis with neutrophilia and 
lymphopenia.
• Mild to severe anemia.
• High total plasma protein, specifically 
globulin fraction (serum albumin : globulin 
typically <0.8).
• Hyperbilirubinemia and hyperbilirubinuria.
• Serum antibody tests—detect antibodies 
against FCoV; positive tests not diagnostic of 
FIP (indicate only previous FECV infection); 
likelihood of FIP increases with titers ≥1 : 3200, 
but low titers do not exclude FIP .
• RT-PCR—detect viral genome; positive tests 
on blood or stool not diagnostic of FIP; 
positive tests on effusion or tissues confirm FIP .
• Immunohistochemistry—detect virus in 
biopsy or tissue samples; excellent for 
confirming cause of specific lesions, especially 
abdominal disease, which often is not 
diagnosed as FIP .
IMAGING
• May confirm abdominal and pleural effusions.
• May detect granulomatous lesions.
• Thoracocentesis and/or abdominocentesis—
fluid pale to straw colored, viscous with flecks 
of fibrin, specific gravity 1.017–1.047; fluid 
may be used for RT-PCR or immuno- 
histochemistry.
• Laparoscopy—to observe specific lesions of 
peritoneal cavity and obtain biopsy samples.
• Exploratory laparotomy—may be indicated 
for difficult-to-diagnose patients.
Gross
• Variable, patient generally emaciated, with 
rough hair coat.

Canine and Feline, Seventh Edition  511
F
F• Abdomen and/or thoracic cavity—may 
contain thick, viscous exudates.
• White, rough, pyogranulomatous plaques 
or granulomas—may be on serosal surface of 
abdominal organs and omentum; fibrous 
strands may extend between organs.
• Discolored iris with anterior uveitis—may 
see keratic precipitates.
• Lesions in brain and/or spinal cord possible
Histopathologic
• Granulomas or pyogranulomas in any 
affected tissue.
• Lesions—perivascular; increase in size, 
involving large portions of tissue; microscopic 
appearance suggests diagnosis.
  TREATMENT
Inpatient or outpatient, depending on 
severity of disease and owner’s willingness and 
ability to provide good supportive care.
• Therapeutic paracentesis—to relieve pressure/
dyspnea from ascites or pleural effusions.
• Encourage cat to eat.
ACTIVITY
FIP transmission to other cats unlikely; no or 
low levels of FIPV shedding.
DIET
Any food that will entice patient to eat.
• Discuss various aspects of disease, including 
grave prognosis; once clinical FIP is confirmed, 
nearly 100% of cats will die of disease.
• Inform client of high prevalence of FECV 
infection but low incidence of FIP; <10% of 
FCoV antibody–positive cats <2 years of age 
eventually develop clinical disease.
• Generally none.
• Rarely, inflammatory abdominal disease 
from FIP may cause intestinal obstruction.
• No cure; only symptomatic treatment is 
• Immunosuppressive drugs (e.g., oral 
prednisolone)—may alleviate some 
symptoms.
• Feline omega interferon—unclear 
effectiveness in symptomatic management.
• Antibiotics—generally not necessary.ALTERNATIVE DRUG(S)
Direct-acting antiviral drugs for FIP have 
shown effectiveness in treatment and are 
under development.
  FOLLOW-UP
Monitor for development of pleural effusion 
or neurologic disease.
• Modified live intranasal vaccine—against 
FIPV; low efficacy; cannot rely on vaccination 
alone for control; will produce antibody-
positive cats, complicating monitoring in 
catteries or colonies; not generally 
• Mother/offspring—main method of 
transmission appears to be from asymptomatic 
carrier queens to their kittens at 4–7 weeks of 
age, after maternal immunity wanes; break 
cycle of transmission by early weaning at 4–5 
weeks of age and isolating litter from direct 
contact with other cats, including queen.
• Routine disinfection to reduce FECV 
transmission—premises, cages, and water/
food dishes; common disinfectants readily 
inactivate virus.
• Introduce only FCoV antibody–negative 
cats to catteries or colonies that are free of 
virus.
• Avoid breeding pairs that are prone to 
producing litters that develop FIP .
Pleural effusion may require thoracocentesis; 
supportive care for other clinical signs.
• Clinical course—a few days to several 
months until euthanasia is warranted.
• Prognosis grave once clinical signs occur; 
mortality nearly 100%.
FeLV or FIV-positive cats—more prone to 
developing FIP .
FIPV transmission from mother to offspring 
during pregnancy is presumed rare.
SYNONYMS
• Feline coronaviral polyserositis.
• Feline coronaviral vasculitis.
• Systemic feline coronavirus infection.ABBREVIATIONS
• FCoV = feline coronavirus.
• RT-PCR = reverse-transcription polymerase 
center/health-information/feline-health-topics/
feline-infectious-peritonitis
Addie D, Belák S, Boucraut-Baralon C, et al. 
Feline infectious peritonitis: ABCD 
guidelines on prevention and management. 
J Feline Med Surg 2009, 11:594–604.
Addie D, Jarrett O. Feline coronaviral 
infections. In: Sykes JE, Greene CE, ed., 
ed. St. Louis, MO: Saunders Elsevier, 2011, 
pp. 54–67.
Brown MA, T royer JL, Pecon-Slattery J, et al. 
Genetics and pathogenesis of feline 
infectious peritonitis virus. Emerg Infect 
Dis 2009; 15:1445–1452.
Drechsler V, Alcaraz A, Bossong FJ, et al. 
Feline coronavirus in multicat 
environments. Vet Clin North Am Small 
Anim Pract 2011, 1133–1169.
Hartmann K, Binder C, Hirschberger J, et al. 
Comparison of different tests to diagnose 
feline infectious peritonitis. J Vet Intern 
Med 2003, 17:781–790.
Pederson NC. An update on feline infectious 
peritonitis: diagnostics and therapeutics. Vet 
J 2014b, 201:133–141.
peritonitis: virology and immunopathogenesis. 
Vet J 2014a, 201:123–132.
Richards JR, Elston TH, Ford RB, et al. The 
2006 American Association of Feline 
Practitioners Feline Vaccine Advisory Panel 
Report. J Am Vet Med Assoc 2006, 229: 
1405–1441.
Panel Report. J Feline Med Surg 2013, 
Author  Yunjeong Kim
available online(continued)  Feline Infectious Peritonitis (FIP)

F
512  Blackwell’s Five-Minute Veterinary Consult  
FFeline Ischemic Encephalopathy
  BASICS
• Seasonal neurologic disease that occurs in 
outdoor cats or those with access to outdoors 
in North America during late spring, summer, 
and early fall; usually results in sudden onset 
of seizures, circling, altered mentation, and/or 
blindness; however, any neurologic 
abnormalities can be found in these cats.
• Aberrant migration of Cuterebra  larva in the 
brain of a cat that often causes thrombosis or 
vasospasm of middle cerebral artery with 
ensuing ischemic necrosis; degeneration of 
superficial layers of cerebral cortex and 
parenchymal destruction associated with 
physical migration of larva in brain 
• Must be differentiated from other causes of 
vascular diseases affecting brains of cats as 
well as other neurologic diseases of cats.
• In feline ischemic encephalopathy (FIE), 
Cuterebra  larva enters nasal passage of cat, 
migrates through cribriform plate into 
olfactory bulb of the brain, then along 
olfactory peduncle and sometimes continues 
in parenchyma of brain, or alternatively in 
subarachnoid space; parasite then, if still alive, 
migrates caudally, where it may compromise 
the middle cerebral artery (MCA) physically 
through spines on the larvae’s body, or 
possibly via chemical agent secreted by 
parasite causing vasospasm to vessel; or 
vasospasm may be secondary to hemorrhage 
caused by parasite; parasite may then die in 
subarachnoid space (SAS) or within 
• Adult botfly lays eggs by entrance of 
rodent’s den; eggs hatch into L1 stage of 
larva, which attaches to hair of mouse or 
rabbit and enters body through a normal 
orifice (mouth, nose, eye, or anus) and 
migrates into associated tissues (nasopharynx, 
trachea, thoracic cavity, diaphragm, 
abdominal cavity); then larva continues its 
migration to reach subcutaneous site in 
inguinal or thoracic region where it matures 
first to L2 stage and then within warble to L3 
larval stage, emerges through skin, drops off 
host, pupates in soil over winter, and then 
emerges in spring as an adult botfly. Adult 
lays eggs near entrance of rodent’s den; eggs 
hatch to form L1 larvae… When cat hunts 
near rodent’s den, L1 larva attaches to cat’s 
hair and gains access to nasal passage of cat 
and begins catastrophic pathway of FIE.
• Occasionally larva does not migrate 
through cribriform plate but embeds in nasal 
passage or respiratory tract of cat, causing 
focal respiratory signs; larva has also been 
found in the eye and oropharyngeal region.SYSTEMS AFFECTED
• Brain and less commonly spinal cord.
• Larvae can also be found in skin, nasal passage, 
pharynx, larynx, eye, trachea, and thorax of cats.
GENETICS
None
Not known.
• North America only.
• Same distribution as Cuterebra  botfly.
• Disease not recognized in locations that do not 
have Cuterebra  botfly, such as Australia and Japan.
None
• Median age—2 years old.
• Range—1–7 years old.
None
SIGNS
• Sudden onset of neurologic signs.
• Often preceded by upper respiratory signs 
1–3 weeks prior to neurologic signs (due to 
migration of the parasite in the nasal passage).
• Often prosencephalic signs.
• Most commonly—seizures, circling, altered 
mentation, blindness.
• Sometimes multifocal neurologic signs.
• Rarely spinal cord signs.
• May stop meowing/develop aphasia.
CAUSES
Cuterebra  larvae.
• Outdoor cats; access to outdoors.
• Not reported in indoor only cats.
• July, August, and September in northeast 
United States and southeast Canada; can be found 
in May and June in southeast United States.
• Hunting cats.
  DIAGNOSIS
• Other causes of vascular accidents in brain 
such as renal disease and hyperthyroidism 
with hypertension.
• External trauma.
• T umors—usually progressive rather than 
sudden in onset.
• Infectious/inflammatory diseases—such as 
those caused by Cryptococcus  sp., Toxoplasma 
gondii , feline infectious peritonitis (FIP) virus, 
and feline immunodeficiency virus (FIV).
• CBC—occasionally neutrophilia, 
leukocytosis, or eosinophilia.• Chemistry—occasionally elevated globulins 
or hyperglycemia.
• Serology for feline leukemia virus (FeLV), 
FIV, FIP—negative.
• Cryptococcal antigen titers—negative.
• Toxoplasma immunoglobulin (Ig) G and 
IgM—negative.
IMAGING
• MRI—diagnostic modality of choice; 
detect track lesion extending from cribriform 
plate into olfactory bulb and frontal, parietal, 
and temporal lobes best recognized on dorsal 
sequences; may see abnormalities in ipsilateral 
nasal passage; may also see area of ischemic 
infarction in brain; if performed soon after 
onset of signs, increased signal intensity on 
T2 weighted, proton density weighted, and 
fluid attenuated inversion recovery (FLAIR) 
images associated with ischemia of superficial 
layers of cerebral cortex, or the area supplied 
by MCA; scant parenchymal enhancement in 
area of infarction after administration of 
contrast. If MRI is done more then 2–3 
weeks after onset of signs, may find loss of 
overlying gray matter in region supplied by 
MCA and associated hydrocephalus ex vacuo. 
Magnetic resonance angiography (MRA; time 
of flight or postcontrast) may be of some 
utility in some cases.
• CT—limited value.
Cerebrospinal fluid—normal or nonsuppura-
tive inflammation with macrophages, 
lymphocytes, or eosinophils.
• Local areas of malacia and hemorrhage 
involving olfactory bulbs and peduncles on 
brain transverse sections. Thorough 
examination of nasal passage, cribriform 
plate, olfactory bulbs, and peduncles, as well 
as remaining parenchyma, meninges, and 
overlying calvaria, may reveal the larva, which 
is approximately 5–10 mm in length (stage 2 
larva), tan, and with concentric rings of 
spines along length of body.
• Histopathologic features may include 
necrosis and hemorrhage of parasitic track, or 
less specific findings such as superficial 
laminar cerebrocortical necrosis, cerebral 
infarction, subependymal rarefaction, and 
astrogliosis and subpial astrogliosis.
  TREATMENT
• Padded cage may be necessary if cat is 
having seizures.
• Swivel IV line can be used if patient 
exhibits propulsive/compulsive circling or loss 
of balance.

Canine and Feline, Seventh Edition  513
F
FCLIENT EDUCATION
• Only occurs in outdoor cats and those with 
access to outdoors; strictly indoor cats do not 
develop FIE.
• Only occurs in summer months, with 
majority of patients seen during July, August, 
and September in the northeast United States 
and southeast Canada.
• May not occur in major metropolitan areas 
that do not have normal appropriate hosts 
such as cottontail rabbit.
Successful removal of parasite from the brain/
spinal cord has not been reported in cats, but 
may be possible if neuroimaging is available 
early after onset of clinical signs.
• Supportive care including antiepileptic 
drugs and appropriate fluid supplementation, 
which may include thiamine administration 
and additional potassium IV depending on 
nutritional status of patient; typically 
phenobarbital is used at maintenance dose of 
7.5–15 mg PO/IM/IV q12h/cat; in addition 
phenobarbital can be loaded at a total loading 
dose of 16 mg/kg IV/PO/IM; this dose is 
usually divided over 24–48h (e.g., 4 mg/kg 
q12h for 2 days); then maintenance dose is 
started; diazepam can be used at 2.5–5 mg IV 
to stop cluster seizures or status epilepticus; 
other anticonvulsants, such as levetiracetam, 
may also be utilized.
• Cocktail treatment has been proposed for 
recently affected cats—diphenhydramine IM 
at 4 mg/kg 1–2h before giving ivermectin SC 
at 200–500  μg/kg and prednisolone sodium 
succinate at 30 mg/kg IV; treatment is 
repeated at 24h and 48h after first injection 
of ivermectin; in addition patients receive 
prednisone at 5 mg/cat q12h PO for 14 days 
and enrofloxacin at 22.7 mg PO q12h for 14 
days. Because of concerns of blindness in 
some cats with administration of 
enrofloxacin, pradofloxacin or other 
antibiotics with broad-spectrum utility can be 
considered; ivermectin is not approved for use 
against Cuterebra  larva so appropriate client 
permission must be obtained prior to 
administration; this cocktail treatment is not for patients with clinical signs >1 week as 
parasite is likely already dead.
Do not use ivermectin in cats with known 
No adverse effects from ivermectin have been 
noted; however, anaphylactic or allergic 
reaction could occur if Cuterebra  larva 
suddenly dies and releases possible foreign 
antigens.
Can use dexamethasone instead of 
prednisone.
  FOLLOW-UP
Sequential neurologic evaluations.
• Keep cat indoors.
• Use of monthly fipronil, imidacloprid, 
selamectin, or ivermectin has been suggested 
to prevent infections with Cuterebra  parasite 
in outdoor cats.
• May continue to have uncontrolled seizures.
• May continue to circle compulsively/
propulsively.
• May have behavioral changes such as 
aggression, especially in cats with damage to 
piriform lobe.
• May stop meowing/develop aphasia in 
some cats.
After initial onset, many patients improve and 
become acceptable pets; there may be 
persistent deficits, seizures, circling, and 
undesirable behavior such as aggression; may 
develop aphasia; persistent clinical signs 
depend on damage caused by infarction and 
parasitic migration.
NoneAGE-RELATED FACTORS
N/A
None; however, aberrant Cuterebra  larva 
migration has been reported in humans, most 
commonly as ocular form in children.
SYNONYMS
CNS cuterebriasis.
• FIE = feline ischemic encephalopathy.
• FLAIR = fluid attenuated inversion recovery.
• MCA = middle cerebral artery.
• MRA = magnetic resonance angiography.
• SAS = subarachnoid space.
http://www.neurovideos.vet.cornell.edu 
Videos 14-8, 14-9, 12-20
Bowman DD, Hendrix CM, Lindsay DS, 
et al. Feline Clinical Parasitology. Ames, IA: 
Iowa State University Press, 2002, pp. 
430–439.
ed. St. Louis, MO: Elsevier-Saunders, 2015, 
pp. 433–436, 549–550.
Glass EN, Cornetta AM, de Lahunta A, et al. 
cats with Cuterebra  larvae myiasis of the 
association with feline ischemic 
encephalopathy. Vet Pathol 1998, 
35:330–343.
Authors  Eric N. Glass and Alexander de 
Lahunta
available online(continued)  Feline Ischemic Encephalopathy

F
514  Blackwell’s Five-Minute Veterinary Consult  
FFeline Leukemia Virus (FeLV) Infection
  BASICS
A simple retrovirus ( Gammaretrovirus  genus) 
that causes immunodeficiency and neoplastic 
disease in domestic cats.
• Four subgroups of feline leukemia virus 
(FeLV)—A, B, C, and T; FeLV-A most 
transmissible and present in all isolates; 
FeLV-B arises from recombination of FeLV-A 
env gene with endogenous retroviral 
sequences (50% of isolates); FeLV-C (1% of 
isolates) arises from mutation in env gene 
sequences; FeLV-T infects only T cells.
• Early infection (five stages)—(1) viral replication 
in tonsils and pharyngeal lymph nodes; (2) 
infection of circulating B lymphocytes and 
macrophages that disseminate virus; (3) replication 
in lymphoid tissues, intestinal crypt epithelial cells, 
bone marrow precursor cells; (4) release of infected 
neutrophils and platelets from bone marrow; and 
(5) infection of epithelial and glandular tissues, 
subsequent shedding of virus into saliva, urine.
• Abortive infection —if virus replication 
terminated at stage 1; no viremia.
• Regressive or nonproductive infection —
immune response stops progression at stage 2 
or 3 (4–8 weeks after exposure) and forces 
virus into latency after transient viremia; may 
be reactivated with immune suppression or 
other viral infections.
• Progressive or productive infection —immune 
response not effective, persistent viremia (stages 
4 and 5) from 4–12 weeks after infection.
• T umor induction—DNA provirus 
integrates into cat chromosomal DNA in 
critical regions near oncogenes (e.g., c-myc  or 
genes influencing c-myc  expression); thymic 
lymphosarcoma results.
• Feline sarcoma viruses—FeLV mutants; 
arise by recombination between FeLV and 
host genes; virus–host fusion proteins 
responsible for induction of fibrosarcomas.
• Pathogenesis influenced by presence of 
other viruses (e.g., feline foamy virus, feline 
coronavirus, feline immunodeficiency virus 
[FIV]) or endogenous retroviruses.
• Hemic/lymphatic/immune—bone marrow 
dyscrasia, neoplasia, immunosuppression.
• Nervous—degenerative myelopathy, neoplasia.
• Other body systems—immunosuppression 
with secondary infections or neoplasia.
GENETICS
N/A
• In United States, 2–3% in healthy cat 
population; worldwide infection rate 1–8% in 
healthy cats; 3–4 times greater in clinically ill cats.
• Decline in US prevalence since 1980s.GEOGRAPHIC DISTRIBUTION
Worldwide
Species
Cat
• Prevalence highest between 1 and 6 years 
of age.
• Mean—3 years.
Male : female ratio—1.7 : 1.
SIGNS
• Onset of FeLV-associated disease—months 
to years after infection.
• Associated diseases—non-neoplastic or 
neoplastic; most non-neoplastic or degenerative 
diseases result from immunosuppression.
• Regressive infections may be associated with 
cardiomyopathies, lymphomas, leukemias, 
anemia, other infections.
• Clinical signs of FeLV-induced 
immunodeficiency cannot be distinguished 
from FIV-induced immunodeficiency.
• Outdoor cat.
• Multicat household.
• Depend on type of disease (neoplastic or 
non-neoplastic) and secondary infections.
• Lymphadenomegaly—mild to severe.
• Fever, wasting.
• Upper respiratory tract—rhinitis, 
conjunctivitis, keratitis.
• Persistent diarrhea—bacterial or fungal 
overgrowth, parasite-induced inflammation, 
direct effect on crypt cells.
• Gingivitis, stomatitis, periodontitis.
• Nonresponsive or recurrent infections of 
external ear and skin.
• Lymphoma—risk increased 62-fold in 
FeLV-infected cats; thymic and multicentric; 
extranodal lymphoma can affect eye, 
nervous system.
• Erythroid and myelomonocytic leukemias.
• Fibrosarcomas—coinfection with mutated 
sarcoma virus; frequently young cats.
• Peripheral neuropathies; progressive ataxia.
CAUSES
• Cat-to-cat transmission—close casual 
contact (grooming), shared dishes or litter 
pans, bites.
• Perinatal transmission—transplacental and 
transmammary transmission in >20% of 
surviving kittens from infected queens.
• Age—kittens more susceptible than adults.
• Male—result of behavior.
• Free-roaming.
• Multicat household.  DIAGNOSIS
• FIV.
• Other infections—bacterial, parasitic, viral, 
or fungal.
• Anemia—often severe, often nonregenerative; 
regenerative anemias usually associated with 
Mycoplasma haemofelis  or M. haemominutum  
coinfections.
• Lymphopenia or lymphocytosis.
• Neutropenia—sometimes cyclic; may be 
response to secondary infections or immune-
• Thrombocytopenia and immune-mediated 
hemolytic anemia.
• Biochemistry/urinalysis abnormalities 
depend on affected organs.
• Immunochromatography (lateral flow) and 
ELISA—point-of-care screening, detect 
antigen in plasma, serum, saliva, tears; more 
sensitive than immunofluorescent antibody 
(IFA) for early or transient infection; single 
positive test does not predict persistent 
viremia (retest in 12 weeks); confirm positive 
tests with another method.
• IFA—identify FeLV antigen in leukocytes and 
platelets in fixed smears of whole blood or buffy 
coat; positive result indicates productive bone 
marrow infection; 97% of IFA-positive cats 
persistently infected and viremic for life; antigen 
usually detected by 4 weeks after infection, but 
may be up to 12 weeks; for leukopenic cats, use 
buffy coat smears rather than whole blood 
smears; confirm positive tests.
• FeLV vaccination does not interfere with 
antigen testing.
• PCR for proviral DNA in blood or 
tissue—denotes exposure, confirm with 
antigen test; proviral DNA detectable 1–2 
weeks after infection; proviral loads can 
differentiate cats with regressive versus 
progressive infections.
• Reverse transcription PCR (RT-PCR) for 
viral RNA (virus circulating or replicating 
within cells) in saliva or blood—denotes 
viremia and FeLV shedding; first test to 
become positive as early as 1 week after 
• Multiple tests over several months may be 
needed to clarify FeLV status and whether 
infection progressive or regressive; a few cats 
have persistently discordant ELISA-positive 
and IFA-negative tests or test positive only 
sporadically.
IMAGING
Thymic atrophy (fading kittens); mediastinal mass 
and pleural effusion with thymic lymphoma.

Canine and Feline, Seventh Edition  515
F
FDIAGNOSTIC PROCEDURES
Bone marrow aspiration or biopsy—arrest in 
erythroid differentiation; true aplastic anemia 
with hypocellular bone marrow may be seen; 
some cases of anemia result from myelopthesis.
• Bone marrow hypercellularity with 
neoplastic disease.
• Lymphocytic and plasmacytic infiltrates of 
gingiva, lymph nodes, other lymphoid tissues, 
spleen, kidney, liver.
• Intestinal lesions—feline panleukopenia-
like syndrome.
  TREATMENT
• Outpatient for most cats.
• Inpatient—may be required with severe 
secondary infections, anemia, cachexia.
• Blood transfusions—emergency support; 
may need multiple transfusions; passive 
antibody transfer (if vaccinated donor) 
reduces level of FeLV antigenemia in some.
• Management of secondary and 
opportunistic infections.
Supportive therapy (e.g., parenteral fluids, 
nutritional supplements) as indicated.
ACTIVITY
Normal
DIET
• Keep cats indoors and separated from 
FeLV-negative cats to protect from secondary 
pathogens and prevent spread of FeLV.
• Discuss good nutrition, routine husbandry 
to control secondary infections.
• Biopsy or removal of tumors.
tooth extraction, gingival biopsy.
• Antiretroviral therapy not routinely 
indicated due to inconsistent evidence of 
efficacy and potential adverse effects; immune 
modulator therapy also unproven.
◦ Zidovudine (Retrovir® 5–10 mg/kg PO 
q12h)—clinical improvement, does not 
clear virus.◦ α-interferon (Roferon®-A in saline 30 U/
day PO for 7 days every other week).
◦ Feline recombinant interferon omega 
(Virbagen® Omega 1 million U/kg SC for 
5 days starting days 0, 14, 60)—may increase 
survival rates and improve clinical status.
• Mycoplasma haemofelis  infection—see 
Mycoplasmosis for recommended treatment.
• Lymphoma—management with standard 
chemotherapy protocols; remission periods 
average 3–4 months.
• Myeloproliferative disease, leukemias—
more refractory to treatment.
• Vaccinate for respiratory and enteric 
pathogens based on individual risk assessment. 
Rabies vaccination according to regulatory 
guidelines.
Modified live vaccines—potential for disease 
in severely immunosuppressed cats.
Systemic corticosteroids—potential for 
further immunosuppression.
N/A
Immunomodulatory drugs— Propionibacte-
rium acnes  (ImmunoRegulin® 0.5 mL/cat IV 
once or twice weekly); acemannan (Carrisyn® 
100 mg/cat/day PO).
  FOLLOW-UP
Varies according to clinical manifestations.
• Prevent contact with FeLV-positive cats.
introduction to multicat households.
• Screen blood donor cats for FeLV-regressive 
infections using PCR for proviral DNA.
Vaccines
• Most commercial vaccines induce virus-
neutralizing antibodies, reported efficacy ranges 
from <20% to almost 100%, depending on 
methodology; canarypox–FeLV recombinant 
vaccine does not contain adjuvant.
• Test cats for FeLV before initial vaccination.
• Vaccinate kittens at 8–9 and 12 weeks of 
age; boost at 1 year of age; revaccinate every 
2–3 years if cat is in low risk environment; 
annually if high risk..
Persistently viremic cats: >50% succumb to 
related diseases within 2–3 years after 
infection.  MISCELLANEOUS
• Neoplasia (lymphoid, fibrosarcoma).
• Immune-mediated disease.
• Neonatal kittens—most (70–100%) 
susceptible to infection.
• Older kittens— <30% susceptible to 
infection by 16 weeks of age; may develop 
regressive infections.
Probably low, but controversial.
• Abortions, stillbirths, and fetal resorptions 
occur in about 80% of FeLV-positive queens.
• T ransmission from queen to kittens—in at 
least 20% of live births.
SEE ALSO
• Lymphoma—Cats.
• Myeloproliferative Disorders.
feline-leukaemia-virus-infection
Sykes JE. Feline leukemia virus infection. In: 
Sykes JE, ed., Canine and Feline Infectious 
Diseases. St. Louis, MO: Elsevier Saunders, 
2014, pp. 224–238.
Willett BJ, Hosie MJ. Feline leukaemia virus: 
half a century since its discovery. Vet J 
2013, 195:16–23.
available online(continued)  Feline Leukemia Virus (FeLV) Infection

F
516  Blackwell’s Five-Minute Veterinary Consult  
FFeline Panleukopenia
  BASICS
A viral infection of cats characterized by 
sudden onset, vomiting and diarrhea, severe 
dehydration, and high mortality.
Feline parvovirus (FPV) infects and causes 
acute death of rapidly dividing cells.
• Gastrointestinal—crypt cells of jejunum 
and ileum are destroyed causing blunted villi; 
malabsorption of nutrients; acute vomiting 
and diarrhea; dehydration; and secondary 
bacteremia.
• Hemic/lymphatic/immune—severe 
panleukopenia; atrophy of thymus.
• Nervous and ophthalmic—in neonates, 
rapidly dividing granular cells of cerebellum 
and retinal cells of eye destroyed; cerebellar 
hypoplasia with ataxia and retinal dysplasia 
result.
• Reproductive—in utero infection in 
nonimmune queens leads to fetal death or 
neurologic abnormalities.
GENETICS
N/A
• Unvaccinated populations—most severe 
and important feline infectious disease.
• Routine vaccination—almost total control 
of disease.
• Extremely contagious.
• Extremely stable virus, survives for years on 
contaminated premises.
Worldwide in unvaccinated populations.
Species
• Felidae—all, domestic and exotic.
• Canidae—susceptible to canine parvovirus; 
some exotic canids may be susceptible to 
FPV.
• Mustelidae—especially mink; may be 
susceptible.
• Procyonidae—raccoon and coatimundi; 
None
• Unvaccinated and previously unexposed 
cats of any age can become infected once 
maternal immunity has been lost.
• Kittens 2–6 months of age—most 
susceptible to develop severe disease.
• Adults—often mild or subclinical infection.
N/ASIGNS
• History of recent exposure (e.g., from 
shelter population).
• Newly acquired kitten.
• Kitten 2–4 months old from premises with 
history of feline panleukopenia (FP).
• No vaccination history or last vaccinated 
when <16 weeks of age.
• Sudden onset, with vomiting, diarrhea, 
depression, complete anorexia.
• Mental dullness/lethargy.
• Typical “panleukopenia posture”—
sternum and chin resting on floor, feet 
tucked under body, top of scapulae elevated 
above the back.
• Dehydration—appears rapidly; may be 
severe.
• Body temperature—usually mild to 
moderately increased or decreased in early 
stages; becomes severely low as patients 
become moribund.
• Small intestine—either turgid or flaccid.
• Subclinical or mild infections common, 
especially in adults.
• Ataxia from cerebellar hypoplasia—kittens 
infected in utero or neonatally; evident at 
10–14 days of age and persist for life: 
hypermetria; dysmetria; base‐wide stance; 
alert, afebrile, and otherwise normal; retinal 
dysplasia sometimes seen.
CAUSES
FPV
• Small, single‐stranded DNA virus.
• Single antigenic serotype.
• Antigenic cross‐reactivity with canine parvovirus 
(CPV) type 2 and mink enteritis virus.
• Extremely stable against environmental 
factors, temperature, and most disinfectants.
• Requires a mitotic cell for replication.
CPV Types 2a, 2b, and 2c
• CPV‐2a, CPV‐2b, and CPV‐2c can 
produce FP in domestic and/or exotic cats.
• Properties of CPV similar to FPV.
• Factors that increase mitotic activity of 
small intestinal crypt cells such as intestinal 
parasites or pathogenic bacteria.
• Secondary or coinfections—viral upper 
respiratory infections.
  DIAGNOSIS
• Panleukopenia‐like syndrome of feline 
leukemia virus (FeLV) infection—chronic enteritis and panleukopenia, frequently 
anemia; patient positive for FeLV antigen.
• Salmonellosis—can cause severe gastro­
enteritis; white blood cell (WBC) count 
usually high.
• Acute poisoning—similar to acute disease; 
depression; subnormal temperature; WBC 
count normal.
• Many diseases cause mild clinical signs 
hard to differentiate from mild FP; total 
WBC count always low during acute 
infection with FPV, even in subclinical 
• Panleukopenia—most consistent finding; 
WBC counts usually between 500 and 3,000 
cells/μL during acute disease.
• Biochemical findings usually nonspecific—
hypoproteinemia, hypoalbuminemia, 
hypocholesterolemia possible.
• CPV antigen fecal immunoassay (Cite 
Canine Parvovirus Test Kit, IDEXX Labs)—
not licensed for FP; detects FPV antigen in 
feces.
• Chromatographic test strip—feces for FPV 
and CPV.
• Serologic testing—paired serum samples 
detect rising antibody titer.
• PCR testing–confirms FPV in blood, feces, 
or tissue; positive result with recent modified 
live virus (MLV) vaccination.
• Viral isolation from feces or affected 
tissues (e.g., thymus, small intestine, 
spleen).
• Electron microscopy of feces—detects 
parvovirus, presumably FPV.
Gross
• Rough hair coat, weight loss.
• Severe dehydration.
• Evidence of vomiting and diarrhea.
• Edematous, turgid small intestine.
• Petechial or ecchymotic hemorrhages in 
jejunum and ileum.
• Thymic atrophy.
• Gelatinous or liquid bone marrow.
• In utero or neonatal infection—gross 
hypoplasia of cerebellum.
Microscopic
• Dilated small intestinal crypts with 
sloughing of epithelial cells.
• Shortened and blunt intestinal villi.
• Lymphocytic depletion of follicles of lymph 
nodes, Peyer’s patches, spleen.
• Neonatal and fetal infection—disorientation 
and depletion of granular and Purkinje cells 
of cerebellum.
• Eosinophilic intranuclear inclusions in 
affected tissues during early infection.

Canine and Feline, Seventh Edition  517
FF  TREATMENT
• Main principles of treatment—rehydration; 
antibiotic therapy; supportive care (antiemetics 
and analgesics as needed).
• Inpatient—severe cases.
• Outpatient—mild cases.
• IV fluid therapy—essential in severe cases: 
correct dehydration and provide electrolytes; 
add dextrose if patient is hypoglycemic.
• SC fluids—mild cases without dehydration 
or shock.
• Antiemetic therapy should be considered in 
vomiting patients.
• Whole blood, packed red blood cells, or fresh 
frozen plasma transfusions—if clinical signs of 
anemia are present or serum albumin <2 g/dL.
ACTIVITY
Keep patient indoors during acute disease.
DIET
Temporarily withhold food until vomiting is 
controlled.
• Inform client that current and future cats in 
household must be vaccinated for FPV before 
exposure.
• Inform client that virus will remain 
infectious for years unless environment can be 
adequately disinfected with dilute bleach.
None
Broad‐spectrum antibiotics (e.g., ampicillin 
or ampicillin–sulbactam IV, amoxicillin or 
amoxicillin–clavulanate PO)—counter 
secondary bacteremia from intestinal bacterial 
translocation.
Oral medications until vomiting/
gastroenteritis has been controlled.
None
  FOLLOW‐UP
• Monitor hydration and electrolyte balance 
closely.
• Monitor CBC every 24–48h until recovery.PREVENTION/AVOIDANCE
• Contaminated environments (e.g., cages, 
floors, food and water dishes) should be 
disinfected with 1 : 32 dilution of bleach.
• FPV resistant to most commercial 
Vaccines
• FP vaccines are core vaccines—to be given 
to all cats.
• FP is preventable by routine vaccination of 
kittens.
• MLV vaccines are available for parenteral 
injection or intranasal administration; MLV 
vaccine is preferred, with exceptions, as it may 
provide better protection.
• Inactivated vaccine is available for 
parenteral injection.
• Do not use MLV vaccines in pregnant cats 
or kittens younger than 4 weeks old.
• Immunity—long duration, perhaps even 
for life.
• Kittens—vaccinate as early as 6 weeks of 
age, then every 3–4 weeks until 16–20 weeks 
of age; American Association of Feline 
Practitioners vaccination guidelines now 
recommend the last vaccine to be given when 
kitten is at least 16 weeks old, instead of 12 
weeks, because maternal antibodies may not 
have waned until 16 weeks of age.
• Boosters—1 year after last kitten vaccine; 
then repeat every 3 years.
• Shock, sepsis—severe dehydration, 
hypoglycemia, hypoproteinemia bacterial 
translocation, electrolyte imbalance.
• Chronic enteritis—fungal or other cause.
• Teratogenic effects (cerebellar hypoplasia 
resulting in ataxia for life)—virus infection of 
fetus.
• Concurrent infection with intestinal 
PROGNOSIS
• Most cases acute, lasting only 5–7 days.
• Guarded prognosis during acute disease, 
especially if WBC count <2,000 cells/ μL.
• Approximately 50% mortality has been 
reported.
• If patient survives acute disease, recovery 
usually rapid and uncomplicated.
Viral upper respiratory diseases—feline viral 
rhinotracheitis and feline calicivirus infection.
• Clinical—typically in kittens.
• Subclinical—usually adults.ZOONOTIC POTENTIAL
None
• Unvaccinated pregnant cats at great risk of 
• Fetuses almost always become infected with 
fatal or teratogenic effects, even when dam 
has subclinical infection.
• Fetal resorption, abortion, fetal mummi­
fication, stillbirth, or birth of weak, fading 
kittens.
• Kittens may have cerebellar hypoplasia.
SYNONYMS
• Feline distemper.
• Feline parvovirus infection.
• Feline viral enteritis.
• FP = feline panleukopenia.
Greene CE. Feline enteric viral infections. In: 
Saunders Elsevier, 2012, pp. 80–91.
Kruse BD, Unterer S, Horlacher K, et al. 
Prognostic factors in cats with feline 
panleukopenia. J Vet Intern Med 2010, 
24:1271–1276.
Lappin MR, Veir J, Hawley J. Feline 
panleukopenia virus, feline herpesvirus‐1, 
and feline calicivirus antibody responses in 
seronegative specific pathogen‐free cats after 
a single administration of two different 
modified live FVRCP vaccines. J Feline 
Med Surg 2009, 11:159–162.
Porporato F , Horzinek MC, Hoffman‐
Lehmann R, et al. Survival estimates and 
outcome predictors for shelter cats with 
feline panleukopenia virus infection. J Am 
Vet Med Assoc 2018, 253:188–195.
T ruyen U, Addie D, Belák S, et al. Feline 
panleukopenia: ABCD guidelines on 
Surg 2009, 11:538–546.
Author  Julie M. Walker
available online(continued)  Feline Panleukopenia

518  Blackwell’s Five-Minute Veterinary Consult  
FFeline Paraneoplastic Alopecia
  BASICS
OVERVIEW
• Rare condition characterized by cutaneous 
lesions that serve as markers of internal 
• Most affected cats have pancreatic 
adenocarcinoma with metastases to liver, 
lungs, pleura, and/or peritoneum; reports of 
other neoplasias.
• Link between internal malignancies and 
cutaneous lesions is unknown; may involve 
cytokines producing atrophy of hair follicles.
• Domestic shorthair cats only reported cases. 
Median age—13 years; range: 7–16 years.
SIGNS
• Decrease in appetite followed by rapid 
weight loss and excessive shedding.
• Pruritus—variable; sometimes with 
• Hairs epilate easily leading to severe 
alopecia on ventral neck, abdomen, medial 
thighs; rapidly progressive.
• Stratum corneum may “peel,” leading to 
glistening appearance to skin.
• Alopecic skin is shiny, inelastic, and thin, 
but not fragile.
• Gray lentigines may develop in alopecic 
areas.
• Footpads may be fissured and/or scaly; 
often painful.
• Majority of cases are associated with 
underlying pancreatic adenocarcinoma.
• Other associated tumor types include 
cholangiocarcinoma, hepatocellular 
carcinoma, intestinal carcinoma, neuro­
endocrine pancreatic neoplasia, and 
hepatosplenic plasma cell tumor.
  DIAGNOSIS
• Hyperadrenocorticism—polyuria, 
polydipsia, and skin fragility.
• Hyperthyroidism—polyphagia.
• Feline symmetrical alopecia—hair loss 
self­induced; not associated with easy epilation.
• Thymoma—skin is thick, scaly, and 
fissured; lymphocytic interface dermatitis; 
radiographs reveal thoracic mass.
• Demodicosis—mites not associated with 
paraneoplastic alopecia.
• Dermatophytosis—hair loss often 
associated with breakage, not spontaneous 
shedding; inappetence and weight loss rare.
• Alopecia areata—rarely involves entire 
ventral surface; inappetence and weight loss 
rare.• Telogen effluvium—not associated with 
miniaturization of hair follicles.
• Skin fragility syndrome—markedly thin 
skin with lacerations; not always associated 
with exfoliation.
• Superficial necrolytic dermatitis—not 
associated with marked exfoliation and 
No consistent abnormalities; may be helpful 
in ruling out other differentials.
• Endocrine (thyroid profiles and 
dexamethasone suppression test)—endocrine 
disease.
• KOH examination of hairs and/or fungal 
culture—dermatophytosis.
• Skin cytology—possible secondary 
Malassezia  infection (causing pruritus).
IMAGING
• Ultrasonography—pancreatic mass and/or 
nodular lesions in liver, intestines, or 
peritoneal cavity; failure to demonstrate 
nodules does not exclude the diagnosis, 
neoplasia may be too small for detection.
• Thoracic radiographs—metastatic lesions in 
lungs or pleural cavity.
• Laparoscopy or exploratory laparotomy—
identify primary and metastatic tumors.
• Skin—nonscarring alopecia; severe atrophy of 
hair follicles and adnexa; miniaturization of 
hair bulbs; mild to severe acanthosis; variable 
absence of stratum corneum; variable mixed 
superficial perivascular infiltrates of neutrophils, 
eosinophils, and mononuclear cells; some have 
secondary Malassezia  infections.
• Primary tumor—usually pancreatic 
adenocarcinoma, rarely primary bile duct 
cholangiocarcinoma, hepatocellular or 
intestinal carcinomas, other pancreatic 
tumors (neuroendocrine), and hepatosplenic 
plasma cell tumor. • Metastatic nodules—
common in liver, lungs, pleura, and 
peritoneum.
  TREATMENT
• Removal of tumor via surgery may be 
curative; prognosis guarded, as majority of 
cases have metastatic disease.
• Chemotherapy or other medications—no 
reported response.
• Affected animals rapidly deteriorate; 
euthanasia should be suggested.
• Supportive care—only if owners refuse to 
consider euthanasia; feed highly palatable, 
nutrient ­dense foods and/or tube feed.  MEDICATIONS
N/A
  FOLLOW-UP
• Progressive deterioration.
• Supportive care—ultrasonography and 
thoracic radiographs may demonstrate 
progression of metastatic disease.
• Death most often occurs within 2–20 
weeks after onset of skin lesions.
SEE ALSO
Adenocarcinoma, Pancreas.
Caporali C, Albanese F , Binanti D, Abramos 
F . T wo cases of feline paraneoplastic alopecia 
associated with a neuroendocrine pancreatic 
neoplasia and a hepatosplenic plasma cell 
tumour. Vet Dermatol 2016, 27:508–513.
Grandt LM, Roethig A, Schroeder S, et al. 
Feline paraneoplastic alopecia associated 
with metastasising intestinal carcinoma. 
J Fel Med Surg 2015, 
1(2):2055116915621582. doi: 
10.1177/2055116915621582
Outerbridge CA. Cutaneous manifestations 
of internal diseases. Vet Clin North Am 
Small Anim Pract 2013, 43:135–152.
Resnick

Canine and Feline, Seventh Edition  519
FFeline Stomatitis—Feline Chronic Gingivostomatitis (FCGS)
  BASICS
OVERVIEW
• Inflammatory response affecting the oral 
cavity in cats.
• FCGS oropharyngeal inflammation is 
classified by location as:
◦ Alveolar mucositis (alveolar stomatitis)—
inflammation of alveolar mucosa (i.e., mucosa 
overlying the alveolar process and extending 
from the mucogingival junction without 
obvious demarcation to the vestibular sulcus 
and to the floor of the mouth).
◦ Caudal mucositis—inflammation of 
mucosa of the caudal oral cavity, bordered 
medially by the palatoglossal folds and 
fauces, dorsally by the hard and soft palate, 
and rostrally by alveolar and buccal mucosa.
◦ Glossitis—inflammation of mucosa of the 
dorsal and/or ventral surface of the tongue.
◦ Stomatitis—inflammation of the mucous 
lining of any of the structures in the mouth; 
in clinical use the term should be reserved 
to describe widespread oral inflammation 
(beyond gingivitis and periodontitis) that 
may also extend into submucosal tissues.
• Cats.
• Purebred breeds predisposed—Abyssinian, 
Persian, Himalayan, Burmese, Siamese, and 
Somali.
SIGNS
• Anorexia—and/or prefers soft food.
• Scruffy hair coat from lack of grooming.
• Erythematous, ulcerative, proliferative 
lesions affecting gingiva, glossopalatine 
arches, tongue, lips, buccal mucosa, and/or 
hard palate.
• Gingival inflammation commonly 
completely surrounds the tooth, compared 
with gingivitis, which usually occurs on 
buccal and labial surfaces.
• May extend to glossopharyngeal arches as 
well as palate.
• Cause unknown; bacterial, viral, and 
immunologic etiologies suspected.
• Significant findings of feline calicivirus; 
however, calicivirus load does not correlate 
with degree of inflammation or prognosis of 
positive therapy.
• Immunosuppression from feline leukemia 
virus (FeLV) or feline immunodeficiency 
virus (FIV) can also lead to poorly responsive 
infections; most affected cats are negative for 
FeLV. Concomitant FIV infection is not 
uncommon.  DIAGNOSIS
• Oral malignancy.
• Eosinophilic granuloma complex.
• Elevated globulin—polyclonal gammopathy 
secondary to antibody production following 
bacterial invasion into periodontal tissues.
• Leukocytosis and eosinophilia may be 
present.
IMAGING
Intraoral radiographs to evaluate periodontal 
disease and tooth resorption.
• Biopsy (especially unilateral lesions) to rule 
out neoplasia—primarily squamous cell 
• Calicivirus, Bartonella , and oral bacterial 
culture and sensitivity testing not 
  TREATMENT
• Prognosis for cats whose lesions do not 
include caudal oral mucosa is better than 
those affected by caudal stomatitis.
• Initial therapy for early cases of alveolar 
mucositis involves dental scaling above and 
below gingiva and treatment (extraction) for 
teeth affected with grades 3 and 4 periodontal 
disease and/or tooth resorption.
• For cases of focal vestibular and alveolar 
mucositis, extraction of locally affected teeth 
in proximity to lesions usually results in 
resolution.
• For cases of moderate to marked caudal 
stomatitis, extraction of all maxillary and 
mandibular teeth (including root fragments) 
or those distal to canines (if no clinical 
evidence of disease affecting canines and 
incisors) resulted in resolution of 
inflammation in ~60% of cases without 
further need for medication, with ~20% of 
cases requiring control with medication, and 
~20% refractory.
• To aid extractions—create a gingival flap in 
all quadrants for exposure; after completely 
elevating all roots, use high-speed drill with 
water spray to create trough of bone where 
roots were, removing most of keratinized 
gingiva, periodontal ligament, and 
periradicular alveolar bone; before suturing, 
“smooth down” alveolar margin to remove 
sharp edges with round or football-shaped 
diamond bur.
• CO2 laser has been effective as treatment 
adjunct during initial care, especially in cases of moderate to marked caudal stomatitis; laser 
helps to remove some of inflamed tissue and 
bacterial load; laser is set to 4 W of 
continuous energy; after shielding airway 
from laser energy with moistened gauze, 
inflamed areas can be rastered; relasering 
recommended monthly for 3 months if 
inflammation persists.
• If patients do not respond to extraction of 
teeth distal to canines, consider trial of 
prednisolone 2 mg/kg every other day to 
control the inflammation, or remove all teeth; 
when extracting teeth, pay meticulous 
attention to removing all dental hard tissue; 
take intraoral radiographs before and after 
surgery; postoperative application of 
fluocinonide 0.05% (Lidex Gel) to gingival 
margin may help healing.
• Refractory cases with extensive proliferative 
lesion in caudal oral cavity and pharynx 
warrant more guarded prognosis.
• Medication and other therapies have been 
used with limited long-term success; lack of 
permanent response to conventional oral 
hygiene, antibiotics, anti-inflammatory drugs, 
and immunosuppressive drugs is typical; 
medications should not be regarded as primary 
method to control oropharyngeal inflammation.
• Antibiotics—clindamycin 5 mg/kg q12h, 
metronidazole, amoxicillin, ampicillin, 
enrofloxacin, tetracycline.
• Corticosteroids—prednisone 2 mg/kg 
initially daily, followed by every other day; 
methylprednisolone acetate 2 mg/kg q7–30 
days may also help control inflammation.
• Gold salts—Solganal 1 mg/kg IM weekly 
until improvement (up to 4 months), then 
every 14–35 days.
• Chlorambucil—2 mg/m2 PO every other 
day or 20 mg/m2 every other week.
• Bovine lactoferrin—40 mg/kg applied to 
oral mucous membranes.
• Interferon—alpha or omega 30 IU/day 
7 days on, 7 days off, indefinitely.
• CO2 laser to decrease inflamed tissue.
• Cyclosporine—2 mg/kg BID.
  FOLLOW-UP
• Recommend 2- and 4-week postoperative 
examinations to determine success of surgical 
• Soft diet should be encouraged for  
2 weeks postoperatively, though some cats 
may not accept any dietary changes well.

520  Blackwell’s Five-Minute Veterinary Consult  
FPREVENTION/AVOIDANCE
N/A
Wound dehiscence; inappetence, refractory 
caudal inflammation.
PROGNOSIS
• Caudal mouth extractions have been 
shown to greatly improve large percentage 
of patients; full-mouth extractions sometimes 
• Refractory cases with extensive 
proliferative lesion in caudal oral cavity 
and pharynx warrant more guarded 
prognosis.  MISCELLANEOUS
• Lymphocytic plasmacytic stomatitis.
• Stomatitis.
Bellows, JE. Feline Dentistry. Oxford: 
Wiley-Blackwell, 2010.Druet I, Hennet P , Relationship between 
Feline calicivirus  load, oral lesions, and 
outcome in feline chronic gingivostomatitis 
(caudal stomatitis): retrospective study in 
104 cats. Front Vet Sci 2017, 4:209. doi: 
10.3389/fvets.2017.00209
Wiggs RB, Lobrise HB. Veterinary Dentistry: 
Principles and Practice. Philadelphia, PA: 
Lippincott-Raven, 1997.
Author  Jan Bellows
available onlineFeline Stomatitis—Feline Chronic Gingivostomatitis (FCGS)  (continued)

Canine and Feline, Seventh Edition  521
FFeline Symmetrical Alopecia
  BASICS
OVERVIEW
• Alopecia in a symmetrical pattern with no 
gross changes in the skin.
• Common clinical presentation in cats.
• Similar manifestation for many different 
underlying disorders.
No age, breed, or sex predilection reported.
SIGNS
• Total to partial hair loss; most often 
symmetrical but can occur in a patchy 
• Areas of the body commonly affected—
ventrum, caudal dorsum, and lateral and 
caudal thighs.
• Affected areas are often those accessible for 
grooming.
• Patchy areas of hair loss (unsymmetrical) on 
distal extremities or body.
• Cutaneous hypersensitivity—flea allergic 
dermatitis, food, atopy.
• Ectoparasites—flea bite dermatitis, 
Cheyletiellosis, Otodectes cynotis .
• Infection—dermatophytosis.
• Neurologic or behavioral—“psychogenic 
alopecia” (uncommon as primary cause of 
symptoms).
• Stress or metabolic—telogen effluvium.
• Neoplasia—pancreatic neoplasia 
(paraneoplastic alopecia).
• Alopecia areata.
• Hyperthyroidism (early sign).
  DIAGNOSIS
Eosinophilia may occur with 
Serum thyroxine—hyperthyroidism.
IMAGING
N/A
• Flea combing—identify fleas, flea 
excrement, or both.
• Microscopic examination of hair—self-
induced hair loss results in broken blunt 
shafts; endogenous hair loss results in tapered 
ends (telogen hairs).
• Fecal examination—excess hair, mites, and 
ova (Cheyletiella ), tapeworm, or fleas.• Food elimination diet trial—adverse 
reactions to food.
• Skin biopsy—confirm/exclude presence of 
underlying cause (e.g., hypersensitivity 
dermatitis vs. psychogenic, or rarely systemic 
disease).
• Cytology of papules or crusts, if present, 
may have large numbers of eosinophils.
• Microscopic examination of skin 
scrapings—ectoparasites.
• Hair plucks (trichogram)—dermatophyte 
arthrospores or Demodex  mites adjacent to 
hair shafts.
• Histopathologic findings—vary depending 
on cause.
• Feline psychogenic alopecia—hair follicles 
and skin normal.
• High numbers of mast cells, eosinophils, 
lymphocytes, or macrophages suggest allergic 
• Alopecia areata—lymphocytic 
inflammation that encircles bulb portions of 
hair follicles; rare.
  TREATMENT
• Management of underlying cause.
• Inform the owner of the diagnostic plan 
and the time it could take to see a response 
(hair coat regrowth).
• Environmental enrichment in cases of true 
psychogenic cause.
• Antihistamines—e.g., chlorpheniramine 
0.5 mg/kg PO q8h; cetirizine 5 mg/cat 
q12–24h.
• Glucocorticosteroid—prednisolone 0.5 mg/
kg PO, tapering/alternate-day therapy.
• Amitriptyline—1–2 mg/kg PO daily.
• Clomipramine hydrochloride—0.5 mg/kg 
q24h.
• Cyclosporine, modified—5–7 mg/kg PO 
daily; tapering therapy.
• Glucocorticosteroids—can cause alopecia, 
diabetes mellitus, polydipsia, polyuria, 
polyphagia, and weight gain; can suppress 
pruritus, making it difficult to determine 
• Withdraw antipruritic medications 
(including glucocorticosteroids) as diagnostic 
tests near completion (e.g., restricted-
ingredient food trials).  FOLLOW-UP
• Frequent examinations are essential in 
confirming differential diagnoses.
• Successful identification of underlying 
cause offers best prognosis, if cause can be 
controlled (e.g., flea bites or food 
hypersensitivity).
https://indoorpet.osu.edu/cats
2018.
Mertens PA, Torres S, Jessen C. The effects of 
clomipramine hydrochloride in cats with 
psychogenic alopecia: a prospective study. 
J Am Anim Hosp Assoc 2006, 
42(5):336–343.
Sawyer LS, Moon-Fanelli AA, Dodman NH. 
Psychogenic alopecia in cats: 11 cases 
(1993–1996). J Am Vet Med Assoc 1999, 
214(1):71–74.
Waisglass SE, Landsberg GM, Yager JA, Hall 
JA. Underlying medical conditions in cats 
with presumptive psychogenic alopecia. 
228(11):1705–1709.
Resnick

F522  Blackwell’s Five-Minute Veterinary Consult  
FFeline Tooth Resorption (Odontoclastic Resorption)
  BASICS
Tooth resorption (TR) is resorption of dental 
hard tissues (cementum, dentin, and in late 
stages also enamel).
• Odontoclasts deriving from hematopoietic 
stem cells migrate to the external root surface, 
where they start resorption of cementum and 
dentin.
• TR is often preceded by dentoalveolar 
ankylosis (fusion between alveolar bone and 
the root with disappearance of the periodontal 
ligament space). The alveolar bone (already in 
a state of constant resorption and apposition) 
will then include the tooth in its normal 
remodeling process, which results in 
noninflammatory replacement resorption. If 
TR progresses coronally and emerges at the 
gingival margin, an inflammatory component 
through contact with oral bacteria joins the 
initially noninflammatory process, and 
inflamed granulation tissue may form to 
cover defects in the crown of the tooth 
(inflammatory resorption).
• TR in cats most commonly starts anywhere 
on the external root (not crown) surface and 
not just close to the cementoenamel junction.
At least one-third of cats may develop TR 
during life, with the risk of developing TR 
increasing with age. Reported prevalence 
(25–75%) greatly depends on the population 
of animals investigated (general practice 
versus dental specialist practice) and the 
diagnostic methods applied (observation only, 
tactile exploration with an instrument, and/or 
use of dental radiography).
Species
Cats
Persian longhaired cats reported to have TR 
at a younger age compared with other breeds.
Rarely seen in cats less than 2 years of age; 
first teeth usually affected at 4–6 years of age.
SIGNS
Most affected cats do not show clinical signs, 
in particular when teeth are affected by 
replacement resorption only (which is 
asymptomatic) and the TR is located apical to 
the gingival attachment (not yet exposed to 
oral bacteria); some show dropping of food while eating, reluctance to eat hard food, and 
repetitive lower jaw motions (“chattering”).
• Dental deposits, hyperplastic gingiva, and 
granulation tissue often cover a clinically 
evident TR emerging at the gingival margin. 
A dental explorer can be used under general 
anesthesia to detect irregularities at the tooth 
surface near the gingival margin.
• TR occurs more often on the labial and 
buccal aspects of premolar and molar teeth, 
and less commonly on canine and incisor 
teeth. The mandibular third premolar teeth 
are usually the first teeth affected by TR.
• Canine teeth (in particular maxillary) often 
appear to extrude excessively (abnormal tooth 
extrusion), leading to exposure of the root 
surface. Thickening of alveolar bone with 
local osteomyelitis (alveolar bone expansion) 
is often associated with this phenomenon.
Classification of Tooth Resorption
• American Veterinary Dental College 
(AVDC) currently suggests classification based 
on the severity (stages 1–5) and radiographic 
appearance of the resorption (types 1–3):
◦ Stage 1 (TR1)—mild dental hard tissue 
loss (cementum or cementum and enamel).
◦ Stage 2 (TR2)—moderate dental hard 
tissue loss (cementum or cementum and 
enamel with loss of dentin that does not 
extend to the pulp cavity).
◦ Stage 3 (TR3)—deep dental hard tissue 
loss (cementum or cementum and enamel 
with loss of dentin that extends to the pulp 
cavity) with most of the tooth still retaining 
◦ Stage 4 (TR4)—extensive dental hard tissue 
cavity) with most of the tooth having lost its 
integrity; there are substages TR4a (crown and 
root equally affected), TR4b (crown more 
severely affected than root, and TR4c (root 
more severely affected than crown).
◦ Stage 5 (TR5)—remnants of dental hard 
tissue are visible only as irregular 
radiopacities with complete gingival 
covering.
• See Imaging for additional classification 
scheme (types 1–3).
CAUSES
• Etiology is unknown; possibly multifactorial 
(e.g., nutritional, inflammatory, and hereditary).
• One hypothesis is that chronic dietary intake 
of excess vitamin D would lead to periodontal 
ligament degeneration, hypercementosis, 
hyperosteoidosis, narrowing of the periodontal 
ligament space, dentoalveolar ankylosis, and 
replacement resorption. If such a process 
occurred close to the gingival attachment, an 
inflammatory component would join the 
initially noninflammatory disease.  DIAGNOSIS
Periodontal disease, stomatitis.
IMAGING
• Without dental radiography, TR below the 
gingival attachment (and thus the vast 
majority of TR) will not be detectable.
• On a radiograph of a tooth with type 1 
resorption, a focal or multifocal radiolucency is 
present in the tooth with otherwise normal 
radiopacity and normal-appearing periodontal 
ligament space. On a radiograph of a tooth 
with type 2 resorption, there is narrowing or 
disappearance of the periodontal ligament space 
in at least some areas and decreased radiopacity 
of part of the tooth. On a radiograph of a tooth 
with type 3 resorption, features of both type 1 
and type 2 resorptions are present in the same 
tooth; the affected tooth shows areas of normal 
and narrow or lost periodontal ligament space, 
and there is focal or multifocal radiolucency in 
the tooth and decreased radiopacity in other 
areas of the tooth.
• For example, a clinically evident TR 
emerging at the gingival margin 
(inflammatory resorption) will generally be 
visible as a notched radiolucency in the tooth 
with sharp or scalloped margins (type 1 
resorption). The periodontal ligament space 
may be of normal width apical to the TR, but 
there will be horizontal or vertical loss of 
alveolar bone adjacent to the TR. Lesions on 
mesial and distal tooth surfaces or in the 
furcation area usually are more obvious on 
radiographs than those on labial/buccal and 
lingual/palatal tooth surfaces.
• Fusion of the root and alveolar bone 
(dentoalveolar ankylosis) results in focalized 
or generalized disappearance of the 
periodontal ligament space and lamina dura 
on radiographs. Resorbed dental tissue will 
gradually be replaced by bone (replacement 
resorption). The root will take on a striated or 
moth-eaten appearance (“ghost roots”), and 
the periodontal ligament space and lamina 
dura will disappear on radiographs (type 2 
resorption). Unlike inflammatory resorption, 
adjacent bone usually is not resorbed.
  TREATMENT
DIET
Add water to hard kibble to soften it.
Daily tooth brushing or other means of home 
oral hygiene may help control plaque and 
allow for earlier detection of teeth affected 
by TR.

Canine and Feline, Seventh Edition  523
F
FSURGICAL CONSIDERATIONS
• The treatment of choice for teeth with TR 
is complete extraction. Multirooted teeth are 
sectioned after creation of a flap and removal 
of alveolar bone on labial and buccal aspects 
of the roots so that each single-rooted crown–
root segment can be elevated and removed. 
Resorbing root remnants under noninflamed 
and intact gingiva (often appearing as a small 
gingival bulge) and without periapical 
pathology on dental radiographs may be left 
where they are. However, root remnants 
underneath inflamed gingiva with sinus tracts 
must be extracted.
• Teeth with dentoalveolar ankylosis and 
replacement resorption can be treated by means 
of crown amputation and intentional retention 
of resorbing root tissue. A flap is made, the 
crown is removed with a water-cooled round 
bur to, or slightly below, the level of the alveolar 
margin, and the wound is rinsed and closed by 
suturing. Contraindications include 
periodontitis, endodontic and periapical 
disease, and stomatitis.
• Canine teeth exhibiting moderate to severe 
abnormal extrusion and alveolar bone 
expansion should be treated with an open extraction so that a flap can be used to close 
the wound.
Topical chlorhexidine or zinc ascorbate gel 
applied to the mouth once a day.
  FOLLOW-UP
• Recommend 2-week postoperative 
examination to determine success of surgical 
• Soft diet should be encouraged for 2 weeks 
postoperatively, though some cats may not 
accept any dietary changes well.
N/A
Wound dehiscence.EXPECTED COURSE AND PROGNOSIS
Additional teeth may develop TR in the 
future, so monitoring with dental radiographs 
is warranted.
SYNONYMS
Feline odontoclastic resorptive lesion 
(FORL).
• TR = Tooth resorption.
Author  Alexander M. Reiter
Jan Bellows.
available online(continued)  Feline Tooth Resorption (Odontoclastic Resorption)

F524  Blackwell’s Five-Minute Veterinary Consult  
FFeline (Upper) Respiratory Infections
  BASICS
• Viral, bacterial, fungal etiologies.
• Most cats harbor viral causes and become 
clinical with stress.
• Viral upper respiratory infection (URI) very 
common, secondary bacterial infections 
common; primary bacterial rhinitis uncommon.
• Most organisms spread through direct 
contact, air (droplets from coughing, 
sneezing, or discharge), and contaminated 
surfaces (e.g., shared bowls, cages).
• Illness typified by rhinosinusitis, conjunctivitis, 
lacrimation, salivation, oral ulcerations.
• Feline herpesvirus (FHV) induces marked 
rhinitis, sneezing, and conjunctivitis, and may 
lead to chronic signs; cats are infected for life, 
with latent virus sequestered in trigeminal 
nerve ganglion.
• FHV infects epithelial cells of respiratory 
tract, conjunctiva, and/or cornea; during 
primary infection or recrudescence, direct 
effect is cytolysis of infected cells and necrosis 
of affected tissues; inflammatory disease can 
occur via immune-mediated response to 
infection; turbinate lysis can occur.
• Feline calicivirus (FCV) has predilection for 
epithelial cells of oral cavity and upper 
respiratory tract; causes rhinitis, stomatitis, 
oral ulceration: ulcers start as vesicles; some 
strains infect lungs and can cause focal 
alveolitis and interstitial pneumonia; other 
strains cause “limping syndrome.”
• FCV–virulent systemic disease (VSD) 
caused by hypervirulent strains that can infect 
endothelium of liver, lungs, and pancreas, 
leading to severe systemic illness characterized 
by vasculitis; results in edema, alopecia, 
ulcers, and can cause multiple organ 
dysfunction syndrome (MODS), systemic 
inflammatory response syndrome (SIRS), 
disseminated intravascular coagulation, death.
• Chlamydophila felis  predominantly infects 
conjunctiva and causes conjunctivitis; has also 
been associated with URI.
• Bacterial infection—often secondary to 
viral disease, trauma, allergic rhinitis.
• Cryptococcus  affects rostral nasal cavity 
resulting in rhinitis and turbinate lysis; 
granulomatous protuberances can occur; 
destruction of adjacent facial bones facilitates 
spread of infection to contiguous regions, such 
as bridge and side of nose, nasal planum, or 
hard palate, resulting in facial distortion; 
infection can spread through cribriform plate, 
resulting in meningoencephalitis, cryptococcal 
optic neuritis, secondary retinitis.
• Respiratory—nasal and upper airway, 
including sinuses, lower airway.• Ophthalmologic—conjunctiva.
• Musculoskeletal—FCV.
• Integument/mucous membranes—FHV, 
Cryptococcus .
• Neurologic— Cryptococcus , lymph.
• VSD can affect many organ systems.
GENETICS
N/A
• FHV and FCV most common causes of 
URI.
• Over 90% of cats are seropositive for FHV.
• Conjunctivitis is most common disease 
caused by FHV, most common feline 
ophthalmic disease.
• Carrier states exist for FHV, FCV (10–75%).
• C. felis —1–5% for cats without signs of 
respiratory tract disease, 10–30% for cats 
with conjunctivitis or URI.
• Bordetella bronchiseptica— seroprevalence of 
24–79%, isolation rates up to 47% reported.
• Ubiquitous.
• Cryptococcus —worldwide, associated with 
pigeon guano.
• Species—cat.
• Breed predilection—N/A.
• Mean age/range—more common in 
younger cats, though viral flare-ups can occur 
through life.
SIGNS
• Exposure to other cats common; stress, 
steroids, immunosuppression may precipitate 
clinical signs for viral causes.
• Caretakers may report upper respiratory 
signs, weight loss, anorexia, gagging, halitosis, 
depression.
• Depend on organism.
• Frequently—sneezing, nasal discharge, 
stertor, halitosis, ocular discharge, inappetence.
• FHV—fever, sneezing, nasal discharge, 
conjunctivitis, ulcerative stomatitis, ulcerative 
keratitis, blepharospasm, salivation, 
depression, anorexia.
• FCV—fever, salivation and ulceration of 
tongue, hard palate, or nostrils, stomatitis, 
gingivitis, rhinitis, conjunctivitis, coughing, 
dyspnea, lameness.
• With VSD—peripheral edema, dermal 
ulcers, icterus possible.
• B. bronchiseptica —fever, sneezing, ocular 
discharge, nasal discharge, lymphadenopathy, 
coughing, dyspnea, cyanosis.
• Cryptococcus —sneezing, nasal discharge, 
ocular discharge, gagging, dysphagia, stertor, 
upper airway obstruction, facial deformity, 
lymphadenopathy, neurologic abnormalities, 
optic neuritis, chorioretinitis.• C. felis —conjunctivitis, occasional sneeze, 
fever.
• Mycoplasma  spp.—conjunctivitis, ocular 
and nasal discharge, dyspnea.
CAUSES
• Viral—FHV, FCV, influenza.
• Primary bacterial— B. bronchiseptica , C. 
felis, Streptococcus canis , Mycoplasma  spp.
• Secondary bacterial invaders—
Corynebacterium  spp., Escherichia coli , 
Pasturella multocida , Pseudomonas aeruginosa , 
Streptococcus  spp., Staphylococcus  spp.
• Fungal— Cryptococcus neoformans , 
Sporothrix schenckii , Aspergillus  spp., 
Penicillium  spp.
• Stress/steroids.
• Decreased immune function, feline 
immunodeficiency virus (FIV)/feline 
leukemia virus (FeLV) infection.
• Multicat households, shelters, young cats.
  DIAGNOSIS
• Direct fluorescent staining of conjunctival 
scraping—FHV.
• PCR for B. bronchiseptica  (controversial if 
positive), Chlamydophila felis , FCV, FHV, 
H7N2 influenza virus, influenza A virus 
(including H7N2, H3N2, H1N1, H3N8), 
Mycoplasma felis .
• Viral isolation.
• Mycoplasma culture.
• Cryptococcus —direct microscopic 
visualization of organisms in nasal discharge 
or tissue: cytology or histopathology, culture, 
serology; latex agglutination to identify 
antigen.
• Nasopharyngeal polyps.
• Nasopharyngeal stenosis.
• Dental disease—tooth root abscess.
• Anatomic defects.
• T rauma.
• Burn—caustic agent or electrical.
Generally normal with most etiologies—with 
virulent systemic FCV may see inflammatory 
leukogram, thrombocytopenia, elevated liver 
enzymes/total bilirubin.
• Culture of upper airways.
• Lymph node cytology.
• Nasal biopsies.
IMAGING
• Skull radiographs generally not helpful.
• Thoracic radiography—generally normal, 
may see pulmonary involvement if fungal 
disease or pneumonia.

Canine and Feline, Seventh Edition  525
F
F• CT of head—may show mass, turbinate 
lysis, increased soft tissue within nasal 
passages, lymphadenopathy.
• Conjunctival scraping may identify FHV.
• Rhinoscopy—in cats with Cryptococcus .
• Upper airway exam.
• Bronchoalveolar lavage if pneumonia 
• FIV antibody, FeLV antigen testing.
Histopathology—lymphoplasmacytic stomatitis: 
FCV; vasculitis: FCV–VSD; bacterial rhinitis, 
suppurative inflammation; Cryptococcus  
organisms on nasal or lymph node biopsy.
  TREATMENT
• Most cats managed as outpatient; isolate if 
hospitalized, as many organisms highly 
contagious and airborne.
• Moderate to severely affected cats may 
require IV fluids for hydration.
• May require supplemental oxygen.
ACTIVITY
N/A
DIET
• Enteral feeding recommended if anorexia 
persists >48 hours.
• Nasogastric feeding may not be appropriate 
if there is severe nasal discharge.
• Cats with severe oral ulceration may need 
enteric feeding while ulcers heal.
Most agents are contagious.
Corneal ulcers can be deep, may require 
• Many cases will self-resolve.
• Antibiotics not recommended for cats with 
only serous discharge; observation without 
antibiotics recommended for up to 10 days for 
acute-onset mucopurulent/purulent discharge 
without systemic signs (fever, lethargy, 
anorexia) or specific etiology identified by 
exam or history; susceptibility profiles of 
organism may be helpful for chronic cases.◦ First choices—doxycycline 10 mg/kg PO 
q24h, usually effective for B. bronchiseptica , 
C. felis , Mycoplasma  spp.; amoxicillin 
22 mg/kg, PO, q12h.
◦ Other options—amoxicillin–clavulanate 
15–20 mg/kg PO q12h, azithromycin 
5–15 mg/kg PO q24h, marbofloxacin 
2.5–5 mg/kg PO q24h, pradofloxacin 
5–10 mg/kg PO q24h.
• Antifungals—fluconazole 50 mg/cat PO 
q12–24h, itraconazole 10 mg/kg PO q24h; 
compounded formulations not recommended.
• Antivirals—famciclovir 62.5 mg/cat PO 
q12h, cidofovir topical 0.5% 1 drop OU 
q12h.
Use azole drugs with caution in patients with 
liver disease.
Doxycycline can cause esophagitis and 
esophageal strictures—follow with food and/
or water .
Azole antifungals have many drug 
interactions.
  FOLLOW-UP
• Viral—most cases improve within 1 week; 
could take up to 6 weeks to resolve.
treatment suggest alternative cause.
• FCV, FHV—core vaccines; modified live 
and inactivated virus vaccines give reasonable 
protection, mild clinical signs may be seen; 
vaccines do not prevent infection or viral 
latency, although shedding post challenge 
may be reduced.
• Vaccination against C. felis  and B. 
bronchiseptica  is noncore.
• Do not allow non-immunocompetent 
• Bleach diluted 1 : 30 with water mixed with 
detergent is effective at eliminating most 
respiratory pathogens from environment.
• Septicemia (rare).EXPECTED COURSE AND PROGNOSIS
• Good to excellent; underlying immuno -
suppression may increase susceptibility to 
infection, worsen prognosis.
• FHV—generally, mortality low and prognosis 
good, except for young kittens and aged cats.
• FCV–VSD—poor, mortality >50%.
• B. bronchiseptica  rare cause of zoonotic 
• Human conjunctivitis caused by feline 
chlamydia has been reported.
Animals who are actively ill should not be 
bred. FHV can cause abortions.
SEE ALSO
• Cryptococcosis.
• FHV = feline herpesvirus-1.
• MODS = multiple organ dysfunction 
syndrome.
syndrome.
• VSD = virulent systemic disease.
• URI = upper respiratory infection.
https://catvets.com/guidelines/practice-
guidelines/feline-vaccination-guidelines
Consulting Editor  Amie Koenig(continued)  Feline (Upper) Respiratory Infections

F
526  Blackwell’s Five-Minute Veterinary Consult  
FFever
  BASICS
Higher than normal body temperature 
because of changed thermoregulatory set 
point in hypothalamus; normal body 
temperature in dogs and cats 100.2–102.8 °F 
(37.8–39.3 °C). Fever of unknown origin 
(FUO)—at least 103.5 °F (39.7 °C) on at 
least four occasions over 14-day period and 
illness of 14 days’ duration without obvious 
cause.
Exogenous or endogenous pyrogens reset 
thermoregulatory center to higher tempera-
ture, activating physiologic responses to raise 
body temperature. Physiologic consequences 
include increased metabolic demands, muscle 
catabolism, bone marrow suppression, 
heightened fluid and caloric requirements, 
and possibly disseminated intravascular 
coagulation (DIC) and shock.
• Cardiovascular—tachycardia.
depression, DIC.
• Nervous—cerebral edema, depression.
Species
Some breed-associated conditions may result 
in FUO (e.g., shar-pei fever).
SIGNS
• Fever lowers bacterial division and increases 
immune competence.
• Prolonged fever >105 °F ( >40.5 °C) leads 
to dehydration and anorexia.
• Fevers >106 °F ( >41.1 °C) may lead to 
cerebral edema, bone marrow depression, 
arrhythmia, electrolyte disorders, multiorgan 
damage, DIC.
• Clinical history (e.g., contact with 
infectious agents, lifestyle, travel, recent 
vaccination, drug administration, insect bites, 
previous illness, allergies) and physical 
examination (including retinal examination) 
may help identify underlying disease 
• Fever patterns (e.g., sustained, intermittent) 
rarely helpful.
• Tachycardia.• Tachypnea.
• Hyperemic mucous membranes.
• Shock.
CAUSES
• Viruses—feline leukemia virus (FeLV), 
feline immunodeficiency virus (FIV), parvo, 
distemper, herpes, calici.
• Bacteria—endotoxins, Mycoplasma , 
Bartonella , Leptospira , Borrelia burgdorferi , 
others.
• Systemic fungi— Histoplasma , Blastomyces , 
Coccidioidomyces , Cryptococcus .
• Vector borne— Rickettsia , Borrellia , 
Ehrlichia , Anaplasma , Neorickettsia .
• Parasites and protozoa— Babesia , 
Toxoplasma , aberrant larva migrans, 
Dirofilaria  thromboemboli, Leishmania , 
Cytauxzoon , Hepatozoon , Neospora .
Immune-Mediated Processes
Systemic lupus erythematosus, immune-
mediated hemolytic anemia, immune-  
mediated thrombocytopenia, pemphigus, 
polyarthritis, polymyositis, rheumatoid 
arthritis, vasculitis, hypersensitivity reaction, 
transfusion reaction, infection secondary to 
inherited or acquired immune defects.
Endocrine and Metabolic
Hyperthyroidism, hypoadrenocorticism 
(rare), pheochromocytoma, hyperlipidemia, 
Neoplasia
Lymphoma, myeloproliferative disease, 
plasma cell neoplasm, mast cell tumor, 
malignant histiocytosis, metastatic disease, 
necrotic tumor, and solid tumor, particularly 
in liver, kidney, bone, lung, lymph nodes.
Other Inflammatory Conditions
Cholangiohepatitis, hepatic lipidosis, toxic 
hepatopathy, cirrhosis, inflammatory bowel 
disease, pancreatitis, peritonitis, pleuritis, 
granulomatous diseases, portosystemic 
shunting, thrombophlebitis, infarctions, 
pansteatitis, panosteitis panniculitis, 
hypertrophic osteodystrophy, blunt trauma, 
cyclic neutropenia, intracranial lesions, 
pulmonary thromboembolism.
Drugs and Toxins
Tetracycline, sulfonamide, penicillins, 
nitrofurantoin, amphotericin B, barbiturates, 
iodine, atropine, cimetidine, salicylates, 
antihistamines, procainamide, heavy metals.
FUO—Dogs
• Infection (28%)—discospondylitis, fungal 
infections, endocarditis, abscesses, bacteremia, 
septic arthritis, septic meningitis, pyothorax, 
pulmonary foreign body/abscess, stump 
pyometra, pneumonia, osteomyelitis, 
peritonitis, prostatitis, pancreatitis, pyelonephritis, sepsis secondary to 
immunodeficiency, leptospirosis, leishmaniasis, 
toxoplasmosis, Lyme disease, infection with 
Ehrlichia , Anaplasma , Bartonella , others.
• Immune-mediated disease (27%)—
polyarthritis, meningitis, vasculitis, others.
• Bone marrow disease, including neoplasia 
(16%).
• Neoplasia (7%).
• Miscellaneous (10%)—hypertrophic 
osteodystrophy, lymphadenitis, panosteitis, 
portosystemic shunting, shar-pei fever.
• Undiagnosed (12%).
FUO—Cats
• Most virally mediated (e.g., FeLV, FIV, 
feline infectious peritonitis [FIP], less 
commonly parvo, herpes, calici).
• Occult bacterial infection with atypical 
bacteria, sometimes secondary to bite wounds 
(e.g., Yersinia , Mycobacteria , Nocardia , 
Actinomyces , Brucella ).
• Pyothorax.
• Additional causes—pyelonephritis, blunt 
trauma, penetrating intestinal lesion, dental 
abscess, systemic fungal disease, lymphoma, 
solid tumors.
• Immune disorders, endometritis, 
discospondylitis, pneumonia, endocarditis 
rare.
• Recent travel.
• Exposure to biologic agents.
• Very young or old animals.
  DIAGNOSIS
Differentiate fever from hyperthermia. 
Temperatures up to 103 °F (39.4 °C) may be 
caused by stress or illness. Temperatures 
>104 °F ( >40 °C) almost always important. 
Temperatures >107 °F ( >41.7 °C) usually not 
fever, more likely to be primary hyperthermia.
• CBC and blood smear—leukopenia or 
leukocytosis, left shift, monocytosis, 
lymphocytosis, thrombocytopenia or 
thrombocytosis, spherocytes, organisms.
• Biochemistry profile and urinalysis vary 
with organ system involved.
• If infectious disease suspected, attempt to 
culture an organism—urine culture, blood 
cultures (i.e., three anaerobic/aerobic cultures, 
taken 20 min apart; try to use as much 
volume as possible to increase diagnostic yield; 
use special blood culture bottles), fungal and 
cerebrospinal fluid cultures, synovial and 
prostatic fluid, biopsy specimens.

Canine and Feline, Seventh Edition  527
F
F• FeLV and FIV test, Snap 4DX test, 
serologic tests or PCR for Toxoplasma , 
Borrelia , Mycoplasma , Bartonella , Anaplasma , 
Ehrlichia , Rickettsia , FIP , systemic mycoses.
• Fecal examination.
• T racheal wash or bronchoalveolar lavage.
• If immune disorders suspected—cytologic 
examination of synovial fluid; Coombs’ test, 
rheumatoid factor, antinuclear antibodies.
• Pancreatic lipase immunoreactivity.
• T4 in cats.
IMAGING
• Abdominal radiographs—tumors and 
effusion.
• Thoracic radiographs—pneumonia, 
neoplasia, pyothorax.
• Survey skeletal radiographs—bone tumors, 
multiple myeloma, osteomyelitis, discospondylitis, 
panosteitis, hypertrophic osteopathy, 
hypertrophic osteodystrophy.
• Dental/skull radiographs—tooth root abscess, 
sinus infections, foreign bodies, neoplasia.
• Contrast radiography (e.g., gastrointestinal 
and excretory urography).
• Abdominal (plus directed aspirate or 
biopsy)—abdominal neoplasia, abscess or 
other site of infection (e.g., pyelonephritis, 
pancreatitis, pyometra).
• Echocardiography if endocarditis suspected.
Nuclear Imaging
• Radionuclide scanning procedures to 
evaluate for bone tumors, osteomyelitis, 
pulmonary embolism.
• CT, MRI, or positron emission tomography 
scan if indicated.
• Arthrocentesis (culture and cytology).
• Bone marrow aspirate and biopsy if 
malignancy or myelodysplasia suspected.
• Lymph node, skin, or muscle biopsy if 
clinically indicated.
• Fine-needle aspirate or biopsy of any mass 
or abnormal organ.
• Central spinal fluid tap if neurologic signs.
signs.
• Exploratory laparotomy—last resort if all 
other diagnostic tests fail to determine cause 
and patient not improving.
  TREATMENT
Goals of treatment—reset thermoregulatory 
set point to lower level; remove underlying 
cause.NURSING CARE
• Fluid administration (IV) often lowers body 
temperature.
• Topical cooling if fever is severe (convection 
cooling with fans, evaporative cooling with 
alcohol on foot pads, axilla, and groin).
• Only use antipyretic treatment when fever 
is prolonged and life-threatening ( >106 °F , 
>41.1 °C) and topical cooling is unsuccessful. 
Impaired patients (e.g., with heart failure, 
seizures, or respiratory disease) require 
antipyretic treatment earlier. Antipyretic 
treatment may preclude elucidation of cause, 
delay correct treatment, and complicate 
patient monitoring (e.g., reduction of fever is 
important indication of response to 
DIET
Febrile patients in hypercatabolic state require 
high caloric intake.
Work-up of patients with FUO often 
extensive, expensive, and invasive, and may 
not result in definitive diagnosis.
Surgery may be necessary in some animals 
(e.g., pyometra, peritonitis, pyothorax, liver 
abscess, neoplasms).
Do not use broad-spectrum (i.e., “shotgun”) 
treatment in place of thorough diagnostic 
workup unless patient’s status is critical and 
deteriorating rapidly.
• Based on results of bacterial culture or 
serology.
• In emergency situations, combination 
antibiotic therapy can be started after culture 
specimens obtained (e.g., cephalothin 20 mg/
kg IV q6–8h; combined with enrofloxacin 
10 mg/kg IV q24h). Additional antimicrobials 
depend on main clinical suspicion based on 
preliminary laboratory and clinical evidence.
• Do not give antibiotics longer than 1–2 
weeks if ineffective.
Antipyretics
• Aspirin—dogs: 10 mg/kg PO q12h; cats: 
6 mg/kg PO q48h.
• Deracoxib—dogs: 1–2 mg/kg/day.
• Carprofen—dogs: 2 mg/kg q12h.
• Meloxicam—0.1 mg/kg/day.
• Dipyrone—dogs: 25 mg/kg IV.
• Flunixin meglumine—dogs: 0.25 mg/kg 
SC once (give IV fluids).Glucocorticoids
• Do not use unless infectious causes have 
been ruled out.
• May mask clinical signs, may lead to 
immunosuppression, and not recommended 
for use as antipyretics; administration of 
corticosteroids to cats with intractable FUO 
after ruling out infectious diseases may 
promote favorable response.
• Primarily indicated for fever associated with 
immune-mediated disease and certain steroid- 
responsive tumors (e.g., lymphoma).
Side effects of antipyretics include emesis, 
diarrhea, gastrointestinal ulceration, renal 
damage, hemolysis, hepatotoxicity.
Combination of nonsteroidal anti-
inflammatory drugs and steroids raises risk of 
  FOLLOW-UP
• Body temperature at least q12h.
• If cause of fever not found, repeat history 
and physical exam along with screening 
laboratory tests.
• If fever develops or worsens during 
hospitalization, consider nosocomial infection 
or superinfection.
Vary with cause; in some patients (more 
commonly cats), underlying cause cannot be 
• Young animals—infectious disease more 
common; prognosis better.
• Old animals—neoplasia and intra-abdominal 
infection more common; signs tend to be more 
nonspecific; prognosis often guarded.
SYNONYMS
Pyrexia
SEE ALSO
Heat Stroke and Hyperthermia.
• FUO = fever of unknown origin.
Authors  Maria Vianna and Jörg Bucheler 
Consulting Editor  Michael Aherne(continued)  Fever

F
528  Blackwell’s Five-Minute Veterinary Consult  
FFiber-Responsive Large Bowel Diarrhea
  BASICS
OVERVIEW
• A form of chronic idiopathic large bowel 
diarrhea that occurs in dogs and usually 
responds favorably to dietary soluble fiber 
• At the author’s institution, chronic 
idiopathic large bowel diarrhea is diagnosed 
in approximately 25% of dogs referred for 
evaluation of chronic large bowel diarrhea.
• Exclusion diagnosis that requires 
eliminating known causes of chronic large 
bowel diarrhea and clinical response to 
dietary fiber supplementation.
• No pathophysiologic studies have been 
performed.
• Only 3 reports in dogs comprising 83 cases.
• May overlap with a stress-associated poorly 
defined syndrome that has been called irritable 
bowel syndrome, also referred to as nervous 
colitis, spastic colon, or mucus colitis. Some 
dogs with irritable bowel syndrome respond to 
dietary fiber supplementation, while others 
require stress alleviation, antispasmodic 
medications, and/or anti-anxiety drugs.
• Dogs of all ages (0.5–14 years); median 6 
years.
• Many breeds, including mixed breeds; 
common breeds include German shepherd 
dog, miniature schnauzer, cocker spaniel, and 
miniature or toy poodle.
SIGNS
• Chronic diarrhea (soft to liquid) with classic 
large bowel characteristics; tenesmus, excess 
fecal mucus, hematochezia, increased frequency 
(median 3.5 times/day), and urgency.
• Diarrhea usually episodic alternating 
with periods of normal stool; diarrhea may 
be continuous in approximately 25% of 
dogs.
• Less common signs include occasional 
vomiting, decreased appetite during episodes 
of diarrhea, abdominal pain, and anal 
pruritus.
• Weight loss rare.
• Stress factors or abnormal personality 
traits in approximately 35% of dogs; 
household visitation, travel, moving, 
construction, instillation of an invisible 
fence; recent adoption or considered 
nervous, high-strung, sensitive, or 
aggressive; or possess noise phobia, anxiety, 
or depressive disorders.
• Physical examination reveals no significant 
findings related to gastrointestinal tract.
• Digital rectal examination is usually 
normal. Feces may be normal due to episodic 
nature of the disease. Loose stool may be 
present and it may contain hematochezia (red 
blood) or excess mucus.CAUSES & RISK FACTORS
• Unknown; stress or abnormal personality 
traits may play a role in some.
• Clinical response to dietary soluble fiber 
supplementation suggests abnormal colonic 
motility and/or dysbiosis. Dysbiosis is defined 
as a microbial imbalance within the gastro -
intestinal tract. Soluble dietary fiber is a 
prebiotic, fermented by colonic bacteria 
resulting in altered composition or activity of 
bacteria. Prebiotics are not digested by 
mammalian digestive enzymes and “feed” 
colonic bacteria, potentially correcting 
dysbiosis. Soluble fibers also adsorb water, 
improving stool quality. Fermentation of 
soluble fiber by colonic bacteria produces 
volatile fatty acids, which are energy source 
for colonic epithelial cells.
  DIAGNOSIS
• Dietary indiscretion.
• Highly digestible diet-responsive diarrhea.
• Hypoallergenic diet-responsive diarrhea.
• Whipworms.
• Clostridium perfringens –associated diarrhea.
• Lymphocytic plasmacytic colitis.
• Eosinophilic colitis.
• Miscellaneous types of colitis.
• Irritable bowel syndrome.
• Colonic neoplasia (adenocarcinoma, 
lymphoma, and adenoma are most common).
• Cecal inversion.
No consistent or specific abnormalities, 
although can recognize peripheral eosinophilia 
occasionally in dogs with colonic whipworms, 
eosinophilic colitis, and food allergy.
Multiple fecal flotations by zinc sulfate; 
negative for whipworms and other parasites.
IMAGING
• Abdominal radiographs within normal 
limits.
• Abdominal ultrasound within normal 
limits.
• Clostridium perfringens  enterotoxin fecal 
ELISA; negative.
• Therapeutic deworming for whipworms 
(fenbendazole 50 mg/kg PO q24h for 5 
days); no improvement.
• Highly digestible diet trial for 2–3 weeks; 
no improvement in stool quality. During the 
food trial the dog must not receive any other 
nutrients. These diets are highly digestible, 
low in fiber, and restricted in fat. If the dog’s 
stool becomes normal during this diet trial, 
no further diagnostic tests are indicated. The 
highly digestible diet can be fed for another 2–4 weeks and then the original diet can be 
slowly introduced. Some dogs develop 
diarrhea again, others can be maintained on 
their original diet.
• Hypoallergenic diet trial for 2–3 weeks; no 
improvement in stool quality. During the 
nutrients, including flavored heartworm 
preventatives, vitamins, or any other 
supplements. For this diet trial the author 
recommends using a hydrolyzed diet. The 
hydrolyzed protein in these diets is hypo -
allergenic. If the dog’s stool becomes normal 
during this diet trial a diagnosis of dietary 
hypersensitivity or inflammatory bowel 
disease can be made. These hydrolyzed diets 
are also highly digestible, low in fiber, and 
restricted in fat. Some clinicians skip the 
highly digestible diet trial and go directly to 
the hydrolyzed diet trial. Without performing 
a highly digestible diet trial first, response to 
the hydrolyzed diet trial could also be due to 
digestibility, fat, and fiber content and not 
due to dietary hypersensitivity. Many dogs 
that respond to a hypoallergenic food trial can 
be slowly switched back to their original diet 
after 12–14 weeks.
• Colonoscopy; usually within normal 
limits or only mild nonspecific findings 
such as slight increases in mucosal 
granularity or friability.
• Histopathologic evaluation of colonic 
biopsy samples; within normal limits.
• Multiple biopsy samples should be 
evaluated from throughout the colon from 
the cecum to the rectum. Usually at least 5–6 
locations are sampled.
  TREATMENT
• Health care can be provided on an 
outpatient basis and consists of dietary fiber 
• Activity level does not have to be modified.
• A highly digestible “GI” diet should 
initially be supplemented with 1–3 tbsp daily 
of psyllium hydrophobic mucilloid 
(Metamucil 10.2 g psyllium/tbsp).
• Psyllium is a soluble fiber that adsorbs 
water, improving fecal consistency, and acts as 
a prebiotic promoting bacterial fermentation 
and production of volatile fatty acids, which 
are an energy source for colonic epithelial 
cells. Psyllium comes from the seeds or husks 
of the plant ispaghul and consists of 
approximately 90% soluble fiber. Psyllium 
has been shown to be an effective treatment 
in some children with chronic nonspecific 
diarrhea and in other people with several 
diarrheal disorders.
• Median dose is 2 tbsp/day, or 0.13 tbsp/kg/
day, or 1.3 g psyllium/kg/day.

Canine and Feline, Seventh Edition  529
F
F• Initial response to lower amounts of fiber 
supplementation or use of other types of fiber 
is not as successful.
• After 2–3 months without diarrhea, the 
amount of fiber can be slowly reduced 
successfully in approximately 50% of dogs.
• After resolution of diarrhea with psyllium 
supplementation, owners may attempt to 
switch to a commercial high-fiber 
(insoluble fiber) diet that may be more 
convenient to feed; however diarrhea may 
return in 50% of dogs. Insoluble dietary 
fiber helps to distend the colonic lumen; 
distention is necessary for normal fecal 
storage and colonic motility.
supplementation, owners may be able to 
switch from the highly digestible “GI” diet to 
a high-quality maintenance dog food.
• Lack of initial response to fiber supple -
mentation suggests that chronic idiopathic 
large bowel diarrhea may be due to irritable 
bowel syndrome, and pharmacologic 
management of that disorder should be 
instituted.  MEDICATIONS
None indicated.
No known interactions of fiber supplementa-
tion with commonly used drugs.
  FOLLOW-UP
• Patient monitoring requires periodic 
assessment of stool quality, performed during 
recheck office examinations or via telephone 
interviews.
• If stresses were initially identified, stress 
reduction should be attempted.
• If abnormal personality traits were initially 
identified, they should be modified.
• Dietary soluble fiber supplementation can 
occasionally produce excessive flatulence, which 
can be managed by reduction in fiber dosage.• Prognosis is very favorable, as approximately 
85% of dogs have excellent or very good 
long-term response to fiber supplementation.
• There are no known associated conditions.
• Age does not play a role in diagnosis or 
• There is no known zoonotic potential.
• There are no special considerations 
regarding pregnancy, fertility, or breeding.
Lecoindre P , Gaschen FP . Chronic idiopathic 
large bowel diarrhea in the dog. Vet Clin 
North Am 2011, 41:447–456.
Leib M. T reatment of chronic idiopathic large 
bowel diarrhea in dogs with a highly 
digestible diet and soluble fiber: a 
retrospective review of 37 cases. J Vet Int 
Med 2000, 14:27–32.
Author  Michael S. Leib
Consulting Editor  Mark P . Rondeau(continued)  Fiber-Responsive Large Bowel Diarrhea

530  Blackwell’s Five-Minute Veterinary Consult  
FFibrocartilaginous Embolic Myelopathy
  BASICS
Acute ischemic necrosis of the spinal cord 
caused when fibrocartilaginous emboli 
become lodged in the spinal vasculature.
• Emboli—found in spinal cord vasculature; 
histologically and histochemically identical to 
nucleus pulposus of the intervertebral disc.
• Exact mechanism of entry into the spinal 
vasculature unknown.
Nervous
GENETICS
N/A
• Common cause of spinal cord disease in 
nonchondrodystrophic breeds of dogs.
• Rarely reported in chondrodystrophic breeds.
• Uncommon in cats.
Species
• Giant- and large-breed dogs most common, 
but seen in small breeds as well.
• Miniature schnauzers overrepresented.
• Median age 5 years.
• Range: 8 weeks–14.5 years.
Males overrepresented.
SIGNS
• May be associated with trauma or physical 
activity at or immediately before onset of signs.
• Sudden onset, generally nonprogressive and 
nonpainful.
• Discomfort occasionally noted at onset but 
resolves rapidly (minutes to hours).
• Signs of paresis or paralysis develop over a 
matter of seconds, minutes, or hours.
• Condition typically stabilizes within 24 hours.
N/A
• Localization—any spinal cord segment can 
be affected; T3–L3 and L4–S3 most 
common; multifocal lesions may rarely be 
seen; may see spinal shock with T3–L3 
lesions, which can give the appearance of a 
multifocal spinal cord lesion.
• Deficits—commonly lateralized (due to 
spinal vascular anatomy) but can be 
symmetric; contralateral side may be mildly 
affected or normal.• Severity of deficits—related to severity of 
infarction. Most display nonambulatory 
paresis, or plegia with intact nociception; 
fewer patients display ambulatory paresis, or 
plegia with absent nociception.
• Spinal pain—may be present briefly at 
onset of signs (owner report) and generally 
resolves by the time patient is examined.
CAUSES
Unknown
• T rauma/physical activity may precede the 
incident.
• Hyperlipoproteinemia may be a 
comorbidity in miniature schnauzers and 
  DIAGNOSIS
• Acute noncompressive nucleus pulposus 
extrusion (ANNPE)—most important 
clinical difference may be persistent spinal 
pain beyond 24 hours; differentiate with 
cross-sectional imaging; may be 
indistinguishable but treated the same.
• Thrombi/emboli from other sources can 
cause similar ischemic injury to the spinal 
cord—consider underlying predisposing 
conditions (cardiomyopathy, hypothyroidism, 
chronic kidney disease, hypertension, 
hyperlipidemia; especially in cats).
• Intervertebral disc disease; discospondylitis; 
neoplasia; fracture and luxation—typically 
painful with symmetric deficits; survey 
radiography, MRI, CT, and/or myelography 
help confirm the diagnosis.
• Intra- and extramedullary hemorrhage 
secondary to coagulopathy (e.g., anticoagulant 
rodenticide ingestion, thrombocytopenia, or 
disseminated intravascular coagulation)—rule 
out by examining for underlying causes of 
hemorrhage, performing platelet count, and 
determining blood clotting times.
• Infectious/immune-mediated focal 
myelitis—differentiate on progressive history 
and cerebrospinal fluid (CSF) analysis.
• Acute, nonprogressive, asymmetric, and 
nonpainful spinal cord disease—presence of 
these characteristics greatly helps in diagnosis 
of fibrocartilaginous embolic myelopathy 
(FCE).
IMAGING
• Survey spinal radiograph—usually normal, 
used to rule out other causes of myelopathy 
such as fracture, neoplasia, or discospondylitis.
• Myelography and CT myelography—in acute 
stage often demonstrates focal intra  medullary swelling at embolic site; later, often normal or 
shows area of cord atrophy.
• MRI—preferred imaging modality for 
antemortem diagnosis: may see increased 
T2 signal intensity within spinal cord at site 
of lesion; may see mild contrast enhancement.
• Normal or nonspecific changes (mild 
pleocytosis/elevated protein concentration). 
Profound elevations in cell count can 
occasionally be observed with severe necrosis.
• Results depend on location (lumbar vs. 
cerebellomedullary cistern) and time of 
collection in relation to onset of clinical signs.
• Gross—focal spinal cord swelling ± 
• Microscopic—emboli of fibrocartilage in 
arteries and/or veins of spinal cord within 
or near area of focal spinal cord swelling; 
gray matter generally more affected than 
white matter.
• Histologic examination required for 
definitive diagnosis. Presumptive 
antemortem diagnosis is based on typical 
presentation and exclusion of other causes 
of acute myelopathy.
  TREATMENT
Inpatient—for immediate medical treatment 
and diagnostic procedures.
• Keep recumbent patients on padded surface; 
turn frequently to prevent pressure sores.
• Assist and encourage patients to ambulate 
as soon as possible.
• Assist bladder emptying (catheterize or 
express) several times daily if needed.
• Physical rehabilitation therapy may improve 
recovery and reduce residual neurologic 
deficits.
• Sling or harness support for assisted 
walking at home.
ACTIVITY
• Restrict until diagnosis is made in case of 
vertebral column instability from other causes 
such as intervertebral disc herniation or 
fracture/luxation.
• Once FCE is confirmed, activity should be 
encouraged, not restricted.
DIET
Normal unless other general health comor-
bidities are present.
• Gradual recovery from paresis or paralysis; 
most will recover ambulation, but residual 
neurologic deficits are common. Patients who

Canine and Feline, Seventh Edition  531
Fare paraplegic with absent nociception have a 
more guarded prognosis for return of function.
• Most patients need considerable home care 
during recovery, including bladder management.
N/A
No specific medications are indicated for the 
treatment of FCE. Use of steroids such as 
methylprednisolone sodium succinate is 
controversial and unlikely to be of benefit.
Nonsteroidal analgesics should not be 
administered with methylprednisolone 
sodium succinate.
N/A
  FOLLOW-UP
• Sequential neurologic evaluations—during 
first 12–24 hours after initial examination.
• Neurologic status—at 2, 3, and 4 weeks 
after onset of clinical signs.
• Urinary incontinence—manually express 
bladder in patients who are not voluntarily 
urinating. Urinalysis and culture/sensitivity to 
detect urinary tract infection.
• Recurrence highly unlikely but possible.
• No known method of prevention in most 
cases.POSSIBLE COMPLICATIONS
• Fecal and urinary incontinence.
• Urine scalding and pressure sores.
• Generally good prognosis for recovery of 
ambulation.
• Most patients (85%) recover ambulation 
within 3 weeks (range: 3 days–12 weeks).
• Most patients retain some permanent 
neurologic deficits despite recovering 
• Paraplegia with loss of pain perception at 
presentation implies more guarded prognosis.
Disorders that lead to compromise in 
circulatory function may predispose or mimic 
FCE—hyperadrenocorticism; hypothyroid-
ism; high systemic blood pressure; hypervis-
cosity syndrome; hyperlipidemia; bleeding 
diathesis; bacterial endocarditis.
N/A
N/A
High-dose corticosteroid administration—
may cause premature delivery.
• ANNPE = acute noncompressive nucleus 
pulposus extrusion.
• FCE = fibrocartilaginous embolic 
• CSF = cerebrospinal fluid. Suggested Reading
Bartholomew KA, Stover KE, Olby NJ, 
Moore SA. Clinical characteristics of canine 
fibrocartilaginous embolic myelopathy 
(FCE): a systematic review of 393 cases 
(1973–2013). Vet Rec 2016, 179:650.
De Risio L, Adams V, Dennis R, et al. 
Magnetic resonance imaging findings and 
clinical associations in 52 dogs with 
suspected ischemic myelopathy. J Vet Int 
Med 2007, 21:1290–1298.
De Risio L, Platt SR. Fibrocartilaginous 
embolic myelopathy in small animals. Vet 
Clin North Am Small Anim Pract 2010, 
233:129–135.
Gandini G, Cizinauska S, Lang J, et al. 
Fibrocartilaginous embolism in 75 dogs: 
clinical findings and factors influencing the 
recovery rate. J Small Anim Pract 2003, 
44:76–80.
Hawthorne JC, Wallace LJ, Fenner WR, et al. 
Fibrocartilaginous embolic myelopathy in 
miniature schnauzers. J Am Anim Hosp 
Assoc 2001, 37:374–383.
Mikszewski JS, Van Winkle TJ, T roxel MT. 
five cats. J Am Anim Hosp Assoc 2006, 
42:226–233.
Summers BA, Cummings JF , de Lahunta A. 
Veterinary Neuropathology. St Louis, MO: 
Mosby, 1995, pp. 246–249.
Authors  Kristen Bartholomew and Sarah A. 
Moore
Allen Franklin Sisson(continued)  Fibrocartilaginous Embolic Myelopathy

532  Blackwell’s Five-Minute Veterinary Consult  
FFibrosarcoma, Bone
  BASICS
OVERVIEW
• Primary bone fibrosarcoma (FSA) arises 
from stromal elements within the marrow 
cavity and is characterized by malignant 
spindle cells that produce varying amounts of 
collagen but not any osteoid or cartilage.
• In dogs, FSA accounts for <8% of all 
primary bone tumors, with 60% occurring in 
the axial skeleton and 40% arising in the 
appendicular skeleton.
• Bone tumors are rare in cats. FSA is the 
second most common bone tumor in cats and 
can involve the maxilla, mandible, humerus, 
scapula, carpus, digits, ribs, and sacrum.
• Dog and cat; no obvious breed or gender 
predilections in either species.
• Mean age of dogs 9.7 years (range: 2–15 years).
• Affected cats tended to be older, but have 
been reported as young as 1.5 years old.
SIGNS
Appendicular FSA
• Lameness, usually progressive, but occasionally 
acute if there is a pathologic fracture.
• A palpable swelling may be present.
Axial FSA
• Localized swelling with or without pain is 
common; however, anatomic site dependent.
• T umors arising from the mandible or 
maxilla can be associated with halitosis, 
dysphagia, pain on opening the mouth, or 
nasal discharge.
• Vertebral tumors may induce neurologic 
deficits secondary to spinal cord compression.
• Rib tumors are rarely associated with 
respiratory signs unless large and causing 
space-occupying effects. Rib tumors can grow 
asymmetrically, with majority of growth 
occurring within the intrathoracic space.
• For appendicular FSA, lameness and a 
palpable swelling may be present.
• Physical examination findings may be 
variable for FSA for the axial skeleton 
depending on the size and location of the 
tumor; a mass may be visible or palpable.
Unknown
  DIAGNOSIS
chondrosarcoma, hemangiosarcoma, 
histiocytic sarcoma, etc.).• Metastatic bone tumors (transitional cell, 
prostatic, mammary, thyroid, apocrine gland 
anal sac carcinomas).
• T umors that locally invade adjacent bone 
(nasal carcinoma; oral squamous cell 
carcinoma, melanoma, fibrosarcoma, 
ameloblastoma; synovial sarcoma; histiocytic 
sarcoma; digital squamous cell carcinoma, 
melanoma).
• Hematopoietic tumors (myeloma, 
• Bacterial or fungal osteomyelitis.
IMAGING
• Radiographs of the primary lesion show 
features of an aggressive bone lesion (bone 
lysis, cortical destruction, nonhomogenous 
bone formation, ill-defined zone of 
transition).
screen for pulmonary metastasis 
• CT is recommended for axial tumors to 
plan for surgery and/or radiation therapy.
• Histopathology is needed for a definitive 
• Primary bone FSA has been reported to 
metastasize to a variety of locations—lungs, 
regional lymph nodes, other bones, skin, 
kidneys, pericardium, and myocardium. 
Consider additional diagnostic evaluation as 
indicated to rule out metastasis to these or 
other locations.
  TREATMENT
• Amputation is recommended for 
appendicular tumors.
• For axial tumors, wide surgical excision is 
recommended whenever possible. If surgical 
excision is incomplete, adjuvant radiation 
therapy might help improve local control.
• Palliative analgesic therapy is recommended 
for patients with nonresectable local disease 
or gross metastasis, or when definitive therapy 
is declined.
(NSAIDs).
• T ramadol (2–5 mg/kg PO q6–12h).
• Gabapentin (3–10 mg/kg PO q8–24h).
(pamidronate, zoledronate) might alleviate 
bone pain and attenuate bone resorption.• The benefit of adjuvant chemotherapy is 
unknown, but it may be considered for 
high-grade tumors; consult a veterinary 
oncologist for current recommendations.
dogs with renal insufficiency.
• Do not combine NSAIDs with corticosteroids.
  FOLLOW-UP
Physical examination and thoracic radio-
graphs every 2–3 months.
• There is limited information regarding 
long-term prognosis.
• Complete excision of the primary tumor 
can potentially provide long-term control.
• Patients with high-grade primary bone FSA 
may be more likely to develop metastasis.
SEE ALSO
• FSA = fibrosarcoma.
drug.
Albin LW, Berg J, Schelling SH. Fibrosarcoma 
of the canine appendicular skeleton. 
JAAHA 1991, 27:303–309.
Dennis B. Bailey

Canine and Feline, Seventh Edition  533
FFibrosarcoma, Gingiva
  BASICS
OVERVIEW
• Fibrosarcoma (FSA) is a malignant tumor 
of spindle cells that produce varying amounts 
of collagenous (fibrous) extracellular matrix 
and associated stroma.
• Oral FSA arises most commonly in the 
gingiva; occasionally involves lips and rarely 
tongue; invasion into bone is common.
• In dogs, FSA is third most common oral 
malignancy (20% of all oral tumors).
• In cats, FSA is second most common oral 
malignancy (5–15% of all oral tumors).
• Dogs—overall, large-breed dogs are 
predisposed; median age 9 years (range: 1–13 
years).
• Golden retrievers are overrepresented 
specifically for histologically low-grade but 
biologically high-grade FSA variant (see 
Pathologic Findings).
• Cats—no breed predilections; median age 
8–10 years (range: 1–21 years).
SIGNS
• Visible mass arising within oral cavity or 
causing facial deformity.
• Halitosis, hypersalivation, dysphagia, and/
or bloody oral discharge.
• Oral pain—head-shy behavior and/or 
decreased food intake despite showing interest 
in food; change in food preference (favor soft 
vs. hard foods).
• Firm, smooth oral mass with intact 
overlying mucosa is commonly observed.
• Halitosis, hypersalivation, and/or oral 
bleeding.
• Difficulty or pain when opening mouth 
and/or facial deformity.
• Ipsilateral mandibular lymphadenopathy.
• Nasal discharge, epistaxis, or decreased 
nasal air flow (maxillary tumors) can be 
  DIAGNOSIS
• Other malignant oral tumors, including 
melanoma, squamous cell carcinoma, or 
osteosarcoma.
• Benign tumors such as acanthomatous 
ameloblastoma, peripheral odontogenic 
fibroma (epulis), or osteoma.• Tooth root abscess or osteomyelitis.
• Dentigerous cyst.
• Craniomandibular osteopathy (lion’s jaw).
IMAGING
• Skull radiographs recommended to evaluate 
for bone involvement (present in 60–70%).
pulmonary metastasis (uncommon).
extent of local disease and useful for planning 
surgery and/or radiation therapy.
• Cytology or histopathology of ipsilateral 
mandibular lymph node recommended to 
screen for metastasis.
Histologically low-grade yet biologically 
high-grade tumors are a distinct subset of oral 
FSA that tend to occur in large pure-breed 
dogs, particularly golden retrievers. These 
tumors classified as benign lesions (nodular 
fasciitis, chronic inflammatory nodules, 
granulation tissue) or low-grade FSA on 
histopathology. However, aggressive biologic 
behavior, including rapid tumor growth, bone 
destruction (75%), lymph node metastasis 
(20%), and pulmonary metastasis (12%), 
observed in affected dogs.
  TREATMENT
• Surgical excision—removal of mass and 
adjacent bone (maxillectomy or mandibulec-
tomy) with margin of at least 2–3 cm 
recommended whenever anatomically 
possible.
• If tumor margins observed to be incomplete 
or narrow on histopathology, adjuvant 
radiation therapy recommended to improve 
local control.
• Radiation therapy can be considered as sole 
local treatment modality when surgery not 
possible or declined; however, treatment 
intent might not be curative in nature.
(NSAIDs).
• IV aminobisphosphonates might alleviate 
bone pain for dogs treated palliatively.CONTRAINDICATIONS/POSSIBLE 
Use NSAIDs cautiously in all cats and in dogs 
with renal insufficiency.
  FOLLOW-UP
thoracic radiographs every 3–4 months.
progression or recurrence of local disease.
• Overall metastatic rate is 25% (regional 
lymph nodes and lungs).
• Prognosis with surgery alone depends on 
tumor size and location, with reported 
median survival times 9–24 months; long- 
term control is possible with complete 
excision.
• Combining surgery with radiation therapy, 
median survival is 18 months.
• With radiation therapy alone, median 
progression-free survival is 45 months for 
tumors <2 cm, 31 months for tumors 
2–4 cm, and 7 months for tumors >4 cm.
drug.
Ciekot PA, Powers BE, Withrow SJ, et al. 
Histologically low-grade, yet biologically 
high-grade, fibrosarcomas of the mandible 
and maxilla in dogs: 25 cases (1982–1991). 
J Am Vet Med Assoc 1994, 
204(4):610–615.
Gardner H, Fidel J, Haldorson G, et al. 
Canine oral fibrosarcomas: a retrospective 
analysis of 65 cases (1998–2010). Vet 
Comp Oncol 2015, 13(1):40–47.

534  Blackwell’s Five-Minute Veterinary Consult  
FFibrosarcoma, Nasal and Paranasal Sinus
  BASICS
OVERVIEW
• In dogs, FSA accounts for up to 5% of all 
canine sinonasal tumors.
• Nasal FSA uncommon in cats.
• In dogs, no breed or gender predilections 
identified. Median age 9 years (range: 1–16 
years).
• Uncommon in cats—no identified 
predilections.
SIGNS
bilateral involvement.
• Sneezing, stertorous breathing, and/or facial 
deformity.
• Decreased appetite and/or halitosis 
secondary to oral cavity invasion.
• Seizures, behavior changes, and/or obtundation 
secondary to cranial invasion (uncommon).
unilateral but can progress to bilateral.
• Decreased nasal air flow (unilateral or bilateral).
• Pain on nasal or paranasal sinus palpation 
or percussion.
• Facial deformity decreased ocular 
retropulsion, exophthalmia, or epiphora.
• Visible mass effect protruding through 
palate into oral cavity.
  DIAGNOSIS
squamous cell carcinoma, chondrosarcoma, 
osteosarcoma, lymphoma, transmissible venereal 
tumor (dogs), nasopharyngeal polyp (cats).
• Fungal rhinitis—aspergillosis and 
penicilliosis (dogs), Cryptococcus  (cats), 
sporotrichosis (both).
• Rhinosporidiosis (dogs).
• Thrombocytopenia or other coagulopathy.
• Tooth root abscess or oronasal fistula.
helpful.• Coagulation profile.
• Buccal mucosal bleeding time.
IMAGING
• Thoracic radiographs to screen for pulmonary 
metastasis (distant metastases uncommon).
• CT for detecting soft tissue opacity within 
nasal cavity and surrounding sinuses, bony 
destruction, extension through cribriform 
plate into brain.
• If CT scan not accessible, skull radiographs 
can be performed to assess for soft tissue 
opacity in nasal cavity and/or frontal sinuses.
• Blood pressure measurement to rule out 
systemic hypertension as cause for epistaxis.
• Mandibular lymph node cytology to screen 
for possible regional metastasis (uncommon).
• Rhinoscopy helpful for visualization of 
mass or fungal plaque and guiding 
subsequent tissue biopsy.
• Tissue biopsy and histopathology needed 
for definitive diagnosis; biopsy instrument 
should not pass the level of the medial 
canthus of the eye to avoid penetrating the 
cribriform plate.
biopsy preferable if treatment with radiation 
  TREATMENT
• Radiation therapy is treatment of choice.
• Conventional linear accelerator is used most 
radiation treatments and reduce adverse effects 
while maintaining treatment efficacy.
• Palliative radiation protocols (fewer 
advanced disease or if intent of treatment is 
primarily symptomatic.
• Surgery alone is ineffective.
(NSAIDs) for pain control.
• Prednisone (0.5–1 mg/kg PO q24h) to help 
relieve nasal congestion.
• Phenylephrine nasal spray can be used 
intermittently to help with epistaxis.
dogs with renal insufficiency.• Do not combine NSAIDs with 
  FOLLOW-UP
and thoracic radiographs every 3–4 months.
• CT of nasal cavity can be considered to 
monitor disease regression or if clinical signs 
recur or worsen.
• Overall metastatic rate <20% (usually 
involve regional lymph nodes and/or lungs).
• Median survival with palliative care alone 3 
months.
• With definitive radiation therapy, 1-year 
relapse-free survival rate around 50% and 
2-year relapse-free survival rate around 30%.
• Recurrence/progression of tumor and 
recurrence of clinical signs is generally 
life-limiting event for nasal/paranasal FSA.
• Brain involvement is poor prognostic factor.
not a significant prognostic factor.
SEE ALSO
drug.
Sones E, Smith A, Schleis S, et al. Survival 
times for canine intranasal sarcomas treated 
with radiation therapy: 86 cases (1996–
2011). Vet Radiol Ultrasound 2013, 
54(2):194–201.

Canine and Feline, Seventh Edition  535
FFipronil Toxicosis
  BASICS
OVERVIEW
• Phenylpyrazole compound with selective 
toxicity against insects.
• Discovered in 1987, registered as a pesticide in 
the United States in 1996; used worldwide today.
• Blocks chloride passage through 
γ-aminobutyric acid (GABA) and glutamate 
gated chloride channels.
• Except for rabbits, low mammalian 
toxicity—GABA receptors less sensitive and 
lack mammals lack glutamate gated chloride 
channels.
• Uses:
◦ Topical flea and tick spot-on products 
(“plus” versions include S-methoprene).
◦ Roach and ant-bait stations. Flea and tick 
sprays for pets.
◦ Granular turf products.
◦ Soil treatment.
◦ Crop pest control.
Dogs
• Accidental ingestion and/or licking of 
topical spot-on products.
• Chewing ant and roach-bait stations or 
licking gel products.
• Ingesting liquid from bottles or granules 
from bags containing product.
Cats
Accidental ingestion of topical spot-on 
product from grooming.
Rabbits
• Inappropriate application of spot on 
products to rabbits.
SIGNS
• Dermal—skin irritation, alopecia, or 
dermal hypersensitivity reaction.
• Oral—hypersalivation, nausea, vomiting, 
diarrhea.
• Ingestion of large doses—CNS: 
hyperexcitability, tremors, convulsions, 
seizures, death.
Rabbits
Dermal and oral exposure (any amount) can 
cause anorexia, hypersalivation, ataxia, 
tremors, seizures and death.
• Ingestion by dogs, especially young dogs, 
occurs more frequently due to behavioral factors.
• With chronic studies in dogs, severe 
neurotoxic signs were observed at a dose of 
20 mg/kg.
• Wide availability and frequent access to 
products.
• Biggest concern is exposure to concentrated 
products frequently found on farms and 
ranches or used by pesticide control 
applicators.  DIAGNOSIS
• History of exposure.
• Detected in blood, tissue, hair with gas 
chromatography/mass spectrometry (GC/MS).
• Differential diagnosis—dogs and cats: 
exposure to agents that can cause dermal 
hypersensitivity or CNS signs.
  TREATMENT
• Baseline CBC, chemistry profile, and 
urinalysis should be performed to rule out 
preexisting organ dysfunction, which could 
increase the risk for toxicosis.
• For dermal reaction, bathe with liquid 
dishwashing detergent and rinse thoroughly.
• Antihistamine or steroids for dermal 
• With ingestion of a large dose, one dose of 
activated charcoal with sorbitol may be 
beneficial.
• Methocarbamol for tremors.
• Anticonvulsants for seizures.
• IV fluids (balanced crystalloid) at twice 
maintenance if CNS signs occur.
• Activated charcoal 1–2 g/kg PO and an 
osmotic cathartic (sorbitol) × 1 dose for large 
• Methocarbamol for tremors—55–220 mg/kg 
IV; titrate as needed; max daily dose 330 mg/kg/
day (cats and dogs).
• Anticonvulsants for seizures—diazepam 
0.5–1 mg/kg IV (dogs and cats); 
phenobarbital 2–6 mg/kg IV (dogs and cats).
• Diphenhydramine 2–4 mg/kg q8–12h PO; 
0.5–2  mg/kg q8–12h IM/SC/IV.
• Dexamethasone 0.5–1 mg/kg IV/IM 
(dogs); 0.125–0.5 mg/kg IV/IM (cats).
  FOLLOW-UP
Patients usually recover well with 
symptomatic and supportive care; no 
long-term organ damage is expected to occur.
• Puppies/young dogs are less discriminating 
and more likely to chew up product 
• Young and geriatric animals may have lower 
detoxification capabilities.PREGNANCY/FERTILITY/BREEDING
Fipronil was administered to rats (route of 
exposure not included) to determine 
reproductive effects. No reproductive effects 
were noted at 30 ppm (2.54 mg/kg/day in 
males and 2.74 mg/kg/day in females). The 
lowest dosage at which reproductive effects 
were observed was 300 ppm (26.0 mg/kg/day 
in males and 28.4 mg/kg/day in females) 
based on unspecified clinical signs in the 
offspring, reduced litter size, decreased 
bodyweights, decreased mating, reduced 
fertility, reduced postimplantation and 
offspring survival, and delay in physical 
• GC/MS = gas chromatography/mass 
spectrometry.
http://npic.orst.edu/factsheets/fipronil.html
Anadon A, Gupta RC. Fipronil. In: Gupta 
RC, ed., Veterinary Toxicology Basic and 
Clinical Principles, 2nd ed. Waltham, MA: 
Elsevier, 2012, pp. 604–608.
Gupta RC. Fipronil. In: Veterinary 
toxicology: basic and clinical principles. 2nd 
ed. Amsterdam: Elsevier, 2012;604–608.
Hovda LR, Hooser SB. Toxicology of newer 
pesticides for use in dogs and cats. Vet Clin 
32:455–467.
Stern L, Fipronil toxicosis in rabbits, 
DVM360, 10/13/2015.
Wismer T. Novel insecticides: fipronil. In: 
Plumlee KH, ed. Clinical veterinary 
toxicology. St. Louis: Mosby, 2004;183–184.
Author  Sharon L. Rippel

536  Blackwell’s Five-Minute Veterinary Consult  
FFlatulence
  BASICS
The act of expelling gases formed in the 
gastrointestinal (GI) tract through the anus. 
“Flatus” refers to gas formed in the GI tract.
• Passing flatus is a normal physiologic 
function in the dog and cat. Variations in the 
volume, odor, and frequency of the pet’s 
flatus may cause the owner to perceive the act 
of flatulence as a problem.
• Swallowed air (aerophagia), bacterial 
fermentation of nutrients, the interaction of 
gastric acid and pancreatic/salivary 
bicarbonate, and diffusion of gases from 
blood are the main sources of GI gas.
• Odorless gases comprise more than 99% of 
GI gases; these include nitrogen, oxygen, 
hydrogen, carbon dioxide, and methane.
• Malodorous gases containing volatile sulfur 
compounds comprise less than 1% of GI gases; 
these include ammonia, hydrogen sulfide, 
methanethiol, dimethylsulfide, indole, skatole, 
volatile amines, and short-chain fatty acids.
• Dogs and cats lack digestive enzymes to 
cleave oligosaccharides (commonly of vegetable 
source) into absorbable monosaccharides. 
Diets high in oligosaccharides provide 
substrate for colonic microbiota fermentation 
and lead to excessive gas formation.
• Foods containing fermentable fibers 
(including pectins, gums, and carrageenan) 
contribute to flatus directly by fermentation 
of the fiber by colonic microbiota.
• Dogs and cats are lactose intolerant; a 
dietary concentration of 1.5 g/kg/day (there is 
11 g lactose in 1 cup of milk) may produce 
flatulence and diarrhea.
• Hypersensitivity or intolerance to certain 
proteins or carbohydrates is often responsible 
for increased volume or odor of flatus.
• Disease states causing malassimilation of 
nutrients (such as protein-losing enteropathies 
[PLEs] and exocrine pancreatic insufficiency), 
making them available for colonic 
fermentation, can cause increased flatulence.
• Infection with certain enteropathogenic 
organisms, such as Giardia  sp., can cause 
increased flatulence.
• Antibiotics that alter the colonic microbiota 
may cause increased flatulence.
GI
GENETICS
No known genetic basis, although brachy -
cephalic breeds are overrepresented.
Excessive flatulence was reported in 10% of 
dogs in the United States, with 1 out of 4 
experiencing daily episodes.GEOGRAPHIC DISTRIBUTION
N/A
Species
Dog (common); cat (rare).
Excessive aerophagia is seen in brachycephalic 
breeds, sporting dogs, and those with 
gluttonous/competitive eating behavior.
Any age.
None
SIGNS
• “He who smelt it dealt it”—a pet who turns 
around frequently to sniff or look at its rear end.
• Increased frequency, volume, or objectionable 
odor of flatus reported by the pet owner.
• When excessive flatulence is due to 
pancreatic or GI disease, concurrent GI signs 
such as diarrhea, vomiting, borborygmus, 
changes in appetite, and weight loss may be 
present.
• Abdominal discomfort due to GI gas 
distention.
• Increased borborygmus on abdominal 
auscultation or decreased gut sounds 
suggesting ileus.
• Low body condition score may indicate 
underlying pancreatic insufficiency or 
GI disease.
• Obesity may suggest a sedentary lifestyle or 
gluttonous eating habits.
aerophagia, concurrent respiratory signs such 
as excessive panting, increased upper- or 
lower-airway sounds, dyspnea, and tachypnea 
CAUSES
Aerophagia
• Gluttony or competitive eating.
• Respiratory disease or any cause of 
increased respiratory rate or effort.
• Brachycephalic breeds.
Diet-Related
• Diets high in nonabsorbable 
oligosaccharides—soybeans, peas, beans.
• Diets high in fermentable fiber—pectin, 
gums, carrageenan, inulin, psyllium, oat bran.
• Spoiled foods.
• Dairy products.
• Abrupt changes in diet.
Disease Conditions
• Acute and chronic intestinal disease—
including protein-losing enteropathies; 
intestinal dysbiosis; neoplasia; irritable bowel syndrome; parasitism; bacterial, protozoal, or 
viral enteritis; and food allergy or intolerance.
• Exocrine pancreatic insufficiency.
• Nervous, gluttonous, or competitive eating.
• Eating soon after exercise.
• Large-breed dogs.
• Abrupt dietary changes.
• Inappropriate (table food that is likely to be 
fermented) or spoiled foods.
• Lack of regular exercise.
  DIAGNOSIS
• Differential diagnoses include excessive 
aerophagia, dietary factors, motility disorders, 
malabsorption, and changes in the colonic 
microbiota.
• Distinguish dietary and behavioral causes of 
flatus from GI disease by thorough evaluation 
of the patient history; this allows the clinician 
to ascertain the type of diet, amount fed, 
frequency of feeding, frequency of dietary 
changes or additions, the environment in which 
the patient is fed, and frequency of exercise.
Usually normal unless significant pancreatic or 
GI disease is present (e.g., hypoalbuminemia 
in PLE).
• Rectal cytology to evaluate presence of 
neoplasia, parasites, protozoa, or fungal 
organisms.
• Zinc sulfate flotation tests and fecal PCR, 
ELISA, or culture to detect Giardia  sp., 
Tritrichomonas  (cats), and other parasitic, 
bacterial, viral, and protozoal infections.
• Serum trypsin-like immunoreactivity to 
diagnose exocrine pancreatic insufficiency.
• Serum cobalamin and folate concentrations to 
investigate small intestinal malabsorptive disease.
IMAGING
• Thoracic and abdominal radiographs can 
show the distribution of gas in the alimentary 
tract, as well as reveal specific reasons such as 
gastric dilatation volvulus, pulmonary 
infiltrates, and megaesophagus.
• Abdominal ultrasonography to evaluate GI 
thickness and rule out masses.
• Contrast studies may be needed in some 
cases to detect an obstructive pattern and 
provide insight into GI transit time.
• Assessment of gut motility using motility 
capsules and scintigraphic markers may be 
available in certain referral hospitals.
GI biopsy specimens obtained at surgery or 
via endoscopy to detect infiltrative GI disease.

Canine and Feline, Seventh Edition  537
FPATHOLOGIC FINDINGS
N/A
  TREATMENT
Outpatient—treat any underlying pancreatic 
or GI disease.
None
ACTIVITY
Encourage an active lifestyle—exercise 
increases GI motility, which will help decrease 
gas retention and increase regularity of 
DIET
• Feed smaller meals more frequently in an 
isolated, quiet environment.
• Provide interactive/modified feeding 
containers to slow the rate of food intake.
• Change diet to one that is highly digestible, 
with low fermentable fiber and fat content. 
If food intolerance is suspected, consider a 
trial of hydrolyzed protein diet or novel 
protein diet.
• Limit vegetables, which are generally high 
in fermentable fibers, in pet’s diet.
• Encourage a consistent diet.
• Encourage routine exercise.
• Prevent coprophagia by leash-walking and 
cleaning up fecal waste daily.
None
• Carminatives are medications or remedies 
that relieve flatulence; there are few studies to 
show safety or benefit of these drugs in dogs 
or cats.
• Zinc acetate and bismuth are divalent 
cations that bind sulfhydryl compounds (e.g., 
hydrogen sulfide) and can decrease odor of 
flatulence.
• Yucca schidigera  decreases odor by binding 
ammonia and by decreasing the production 
and release of hydrogen sulfide in the 
• Dry activated charcoal adsorbs virtually all 
odiferous gases due to its large surface area.• Inclusion of activated charcoal (0.32 g/5 kg), 
Y. schidigera  (2.45 mg/5 kg), and zinc acetate 
(17 mg/5 kg) in a treat reduced the frequency 
of highly odiferous episodes in dogs.
• Bismuth subsalicylate (dogs: 1 mL/kg/day 
PO, in divided doses) adsorbs hydrogen sulfide 
and has antibacterial properties. Do not use in 
cats due to potential for salicylate toxicity.
• Simethicone (25–200 mg PO q6h) is an 
antifoaming agent that reduces the surface 
tension of gas bubbles, allowing easier 
coalescence and release of intestinal gas; its 
effectiveness in controlling flatulence in 
animals is unknown.
• Pancreatic enzyme supplements reduce 
flatulence in patients with exocrine pancreatic 
• Probiotics, specifically Enterococcus faecium  
SF 68, the probiotic in Purina Veterinary Diets® 
FortiFlora® Canine Nutritional Supplement, 
has been shown to help nutritionally manage 
dogs with flatulence by promoting greater 
beneficial intestinal microflora.
• Nonabsorbed antibacterials such as neomycin 
and rifaximin may have a role in normalizing 
gut microbiota and decreasing flatulence.
Avoid bismuth subsalicylate in cats and in 
dogs with gastroduodenal ulceration and 
bleeding disorders.
N/A
N/A
More than 30 herbal and botanical 
carminatives are available; however, the 
dosage, safety, and efficacy are unknown.
  FOLLOW-UP
Response to therapy.
• Avoid diets high in nonabsorbable 
oligosaccharides and high in fermentable or 
nonfermentable fibers.
• Avoid milk products, spoiled diets, and 
abrupt changes in diet.
• Do not feed shortly after exercise.
NoneEXPECTED COURSE AND PROGNOSIS
N/A
GI disease.
N/A
N/A PREGNANCY/FERTILITY/
BREEDING
N/A
SYNONYMS
N/A
SEE ALSO
• PLE = protein-losing enteropathy.
German AJ. Flatulence. In: Ettinger SJ, 
Feldman EC, Côté E, eds., Textbook of 
Veterinary Internal Medicine, 8th ed. St. 
Louis, MO: Elsevier Saunders, 2017, pp. 
175–178.
Giffard CJ, Collins SB, Stoodley NC. 
Administration of charcoal, Yucca 
schidigera, and zinc acetate to reduce 
malodorous flatulence in dogs. J Am Vet 
Med Assoc. 2001 (281)6:892–896.
Roudebush P . Flatulence. In: Bonagura JD, 
T wedt DC, eds., Kirk’s Current Veterinary 
Therapy XV. St. Louis, MO: Elsevier 
Saunders, 2014, pp. e247–e251.
Waldron, M. GI exchange: a nutritional 
approach to managing dogs with flatulence. 
https://www.purinaproplanvets.com/
media/1155/50174-5_gi_tradecolumn_
nov.pdf
Author  Andrea Wang Munk 
of Debra L. Zoran
available online(continued)  Flatulence

F538  Blackwell’s Five-Minute Veterinary Consult  
F BASICS
Flea bite hypersensitivity (FBH)—allergic 
reaction to antigens in flea saliva.
Flea Life Cycle
• Ctenocephalides felis  (cat flea)—not host 
specific: parasitizes cats, dogs, wildlife. 
• Adult fleas mate on host and within 24 
hours females lay up to 50 eggs per day. 
• Eggs fall off pets into the environment and 
hatch. • Larvae have negative phototropism 
and infest carpets, upholstery, and under 
furniture. • Eggs from wildlife and feral cats 
survive in moist, protected areas. • Larvae 
undergo molts until they pupate; the cocoon 
enhances survival. • Adults emerge when 
environmental conditions and host availabil-
ity are favorable. • Less than 5% of the total 
flea burden is found as adults on the pet. 
• The majority of the biomass is found as 
immature stages in the home and in 
peridomestic areas.
• Antigens in flea saliva cause FBH. • Major 
allergen— Ctef1 , an 18-kD protein. • Flea 
saliva—contains histamine-like compounds 
that irritate skin. • Both immunoglobulin 
(Ig) E and IgG anti-flea antibodies reported. 
• Immediate and delayed hypersensitivity 
reactions reported. • Mast cell degranulation 
follows antigen exposure. • FBH is associated 
with a TH2 response.
Skin
GENETICS
No known inheritance pattern.
• Varies with climatic conditions and flea 
population.
• In areas where fleas are prevalent, FBH is 
considered the most common skin disease.
May occur anywhere; nonseasonal in climates 
that are warm and humid.
Species
None
Typically signs by 5 years of age, but may be 
SIGNS
• Pruritus. • Lack of consistent or effective 
flea control.Physical Examination Findings
• Determined by the severity of the reaction. 
• Finding fleas and flea dirt is supportive but not 
essential for diagnosis. • Sensitive animals require 
a low exposure and tend to o  vergroom, removing 
evidence of infestation. • Dogs—lesions 
concentrated in the caudal-dorsal lumbosacral 
region; caudal-lateral aspect of the thighs, 
lower abdomen, and inguinal region; primary 
lesions are papules; secondary lesions 
(hyperpigmentation, lichenification, alopecia, 
and scaling) and pyotraumatic dermatitis 
(“hotspots”) are common. Erythema and 
papules around the umbilicus are highly 
suggestive (“peri-umbilical rush”) 
• Cats—head and neck pruritic papular 
dermatitis and/or a generalized distribution 
including dorsal lumbosacral area, 
caudomedial thighs, and abdomen. Also 
common clinical signs are self-induced 
symmetrical alopecia and lesions of the 
eosinophilic granuloma complex.
CAUSES
Exposure to fleas; atopy may predispose dogs 
to FBH.
 DIAGNOSIS
• Food allergy. • Atopy. • Ectoparasitism. 
• Dermatophytosis. • Pyoderma. • Any 
pruritic skin disease.
• Usually normal. • Cats—occasional 
• Skin scrapings—negative. • Flea 
c ombings—may find fleas or flea dirt. 
• Intradermal allergen testing (IDT), 
radioallergosorbent test (RAST), and 
ELISA—variable accuracy; both false-positive 
and false-negative results reported.
• Diagnosis based on historical information, 
clinical signs, and response to anti-flea 
treatment. • Fleas or flea dirt is supportive 
but not mandatory. • Identification of 
Dipylidium caninum  segments in stool is 
supportive. • The only way to confirm FBH 
is by response to treatment.
• Superficial perivascular to interstitial 
dermatitis. • Eosinophils often the predomi-
nant cell type.• Eosinophilic intra-epidermal 
microabscesses may be visible. • In cats—
superficial or deep perivascular to interstitial 
dermatitis with numerous eosinophils and 
mast calls. • Histopathologic evaluation—does not differentiate FBH from other 
 TREATMENT
Outpatient therapy.
N/A
DIET
N/A
• Inform owners that there is no cure for FBH; 
flea-allergic animals often become more sensitive 
to flea bites as they age. • Hyposensitization is 
not effective. • Medications that stop itching are 
meant to bring relief while flea control is 
instituted.
Itch Relief
• Anti-inflammatory dosages for s  ymptomatic 
relief while instituting adequate flea control. 
Use only as much as is needed and for the 
shortest duration to achieve the desired effect. 
• Oral—prednisolone: cats, 1–2 mg/kg PO 
q24h for 5–7 days then taper; dogs, 
0.5–1 mg/kg PO q24h for 7 days then taper, 
or for 4 days without tapering.
Oclacitinib
• Anti-itch, mild to moderate anti-inflammatory 
properties approved for allergic itch relief in dogs 
only. Usually a 7–10-day period is enough to 
control the itch while the anti-flea treatment is 
enhanced. • Oral: 0.4–0.6 mg/kg q12h for 14 
days, then reduce frequency to q24h.
Little to no effect.
Flea Control
The most important therapy is the immediate 
reduction or elimination of adult fleas on the 
host. In a highly infested environment, it is 
recommended to treat the surroundings as 
well.
Pet-T argeted Flea Control
• Oral: ⚬ Nitenpyram—adulticide; has the 
fastest onset, but short acting; for dogs q24h, 
for cats q48h. ⚬ Spinosad—monthly oral 
treatment for dogs and cats. ⚬ Isoxazolines—
very effective antiparasitic drugs, lotilaner, 
and sarolaner monthly and fluralaner 
trimonthly. • Topical/spot-on: ⚬ Dinotefuran/
pyriproxyfen—rapid-acting spot-on product 
for dogs and cats; a second canine product Flea Bite Hypersensitivity and Flea Control

Canine and Feline, Seventh Edition  539
F
Fcontains high-dose permethrin and should not 
be used on cats. ⚬ Fipronil plus insect growth 
regulator (IGR)—spot-on treatment for cats 
and dogs (spray treatment for dogs). 
⚬ Imidacloprid plus IGR—monthly spot-on 
treatment for cats and dogs; a second canine 
product contains permethrin and should not 
be used on cats; also available as a collar. 
⚬ Indoxycarb—monthly spot-on, dogs only, 
activated by flea digestive enzymes, contains 
permethrin, should not be used on cats. 
⚬ Selamectin—for dogs and cats, monthly 
spot-on; also has insect development inhibitor 
(IDI) action. ⚬ Selamectin plus sarolaner 
spot-on for cats—monthly spot-on. 
⚬ Fluralaner spot-on for dogs and cats—tri -
monthly treatment. • Sprays—usually contain 
pyrethrins and pyrethroids with IGR.
IGRs
S-methoprene and pyriproxyfen are analogues 
of insect juvenile hormone that bind to 
immature stages and prevent maturation.
IDIs
Lufenuron and selamectin inhibit chitin synthesis 
in egg shell, immature stages, and adults.
Premises-T argeted Flea Control
• Indoor treatment: ⚬ Vacuuming significantly 
reduces the flea burden: removing eggs, larvae, 
and adult fleas; particularly carpets, furniture 
and the floor under furniture. ⚬ “Foggers/
bombs” and premises sprays—contain 
organophosphates, pyrethrins, and/or IGRs. 
Etofenprox plus IGR and permethrin/pyrethrin 
plus IGR, available in inverted aerosol sprays; 
apply according to manufacturer’s directions; 
treat all areas of the house; can be applied by 
the owner. ⚬ Foggers/bombs do not effectively 
penetrate all areas commonly inhabited by fleas 
such as under furniture; handheld sprays are 
highly effective against biomass, may be 
directed where flea populations reside, and have 
long residual activity. • Professional 
e xterminator—discuss products with 
representative.
Environment-T argeted Flea Control
• Outdoor treatment—concentrate in 
shaded areas; sprays usually contain 
pyrethroids or organophosphates and an 
IGR; owners should be educated on areas of 
application based on likelihood of 
r einfestation from feral cats and wildlife. 
• Nematode ( Steinerma carpocapsae )—may kill C. felis  larvae and pupae, but efficacy is 
unknown; no knowledge of the effects these 
worms might have on beneficial insects, 
mammals, or humans.
N/A
• Label instructions—must be strictly followed. 
• Spinosad can potentiate neurologic side 
effects of high-dose i  vermectin—but is safe 
when combined with heartworm preventive 
dose. • Isoxazolines should be used with 
caution in animals with preexisting epilepsy. 
• Pyrethrin/pyrethroid-type flea products—
adverse reactions include depression, h  yper-
salivation, muscle tremors, vomiting, ataxia, 
dyspnea, and anorexia: do not use in cats. 
• Organophosphates—i  nappropriate given the 
current alternatives.
• Powders and dips—adverse reactions and 
toxicity make their use inappropriate given 
the current alternatives. Shampoos containing 
d-limonene on cats can cause acute 
n ecrotizing dermatitis and septicemia. 
• Over-the-counter products often contain 
the same ingredient(s), but the absence of 
proper education frequently leads to failure in 
flea control.
 FOLLOW-UP
• Pruritus—a decrease means the FBH is 
being controlled. • Fleas and flea dirt—
absence is not always a reliable indicator of 
successful treatment.
• Warm climates and infested premises 
require year-round flea control. • Seasonally 
warm climates—begin flea control when 
temperatures consistently remain above 
freezing.
• Secondary bacterial folliculitis. • Acute 
moist dermatitis. • Acral lick dermatitis.
Prognosis is excellent if strict flea control is 
instituted. MISCELLANEOUS
• Anemia—could result from heavy flea burden, 
especially in puppies or kittens. • Dipylidium 
caninum  due to ingestion of the flea.
Package should be consulted for the 
minimum approved age for application.
• Humans can be bitten by fleas; the resulting 
papular rash can be mild to extensive, 
depending on numbers of fleas and individual 
hypersensitivity reactions. • C. felis  can 
transmit zoonotic agents, including B. 
henselae  (cat scratch disease), R. felis  (murine 
typhus, flea-borne typhus), and D. caninum  
(tapeworms).
• Corticosteroids and organophosphates—do 
not use in pregnant bitches and queens. 
• The safe use of sarolaner and afoxolaner has 
not been evaluated in breeding, pregnant, or 
lactating dogs.
SYNONYMS
• Flea bite allergy. • Flea allergy dermatitis.
• ELISA = enzyme-linked immunosorbent assay.
• FBH = flea bite hypersensitivity.
• IDI = insect development inhibitor.
• IDT = intradermal allergen testing.
• IGR = insect growth regulator.
• RAST = ra  dioallergosorbent test.
http://capcvet.org
Rust MK. The biology and ecology of cat 
fleas and advancements in their pest 
management: a review. Insects 2017, 8:118.
Author  Ronnie Kaufmann
Steven A. Levy.
available online(continued)  Flea Bite Hypersensitivity and Flea Control

F
540  Blackwell’s Five-Minute Veterinary Consult  
F BASICS
• Adverse reactions to food affecting the skin. 
• Associated with ingestion of one or more 
substances. • Reaction may be immunologic 
or idiosyncratic.
• Pathogenesis not completely understood. 
• Food hypersensitivity—immediate and 
delayed reactions to specific ingredients 
documented; immediate reactions presumed 
to be type I hypersensitivity reactions; delayed 
presumed to be type III or IV. • Failure or 
prevention of the development of oral 
tolerance to food allergens may encourage 
sensitization. • Food intolerance—nonimmu-
nologic, idiosyncratic reaction; involves 
metabolic, toxic, or pharmacologic effects of 
offending ingredients. • Adverse food 
reaction is the most common term used, and 
does not distinguish between immunologic 
and idiosyncratic reactions. • Adverse food 
reactions patients associated with an increased 
predisposition to atopy. • Cutaneous adverse 
food reactions can trigger flares of atopic 
• Skin/exocrine. • Gastrointestinal. • Nervous.
GENETICS
N/A
• Approximately 5% of all dermatitis and 
10–15% of allergic dermatitis in dogs and cats 
are caused by adverse reactions to food. 
• 13–30% of food allergic dogs have concur -
rent atopy or flea bite hypersensitivity. • Third 
most common pruritic skin disease in the dog; 
second most common in the cat. • Percentages 
vary greatly with clinicians and geographic 
location.
Species
• Dogs—none reported; breeds associated 
with atopic dermatitis overrepresented. 
• Cats—Siamese.
• Any age—dogs: possibly increased 
d evelopment (over other allergic dermatoses) 
in patients <12 months or >7 years of age; 
40% of cases develop at <12 months of age in 
one study; cats: patients <2 years or >5 years of 
age. • Most adult patients have been fed the 
offending allergen for over 2 years prior to 
becoming symptomatic.
None reported.SIGNS
• Symptoms similar to other hypersensitivity 
reactions. • Pruritus is the main dermatologic 
sign.
• Pruritus of any bodily location. • Usually 
nonseasonal. • Poor response to anti-  
inflammatory doses of glucocorticosteroids, 
or oclacitinib or lokivetmab. • Recurrent 
bacterial folliculitis with or without pruritus. 
• Persistent otitis externa. • Concurrent 
gastrointestinal symptoms in a minority of 
cases—vomiting and/or diarrhea, excessive 
b orborygmus, flatulence, and frequent bowel 
movements. • Very rare association of 
neurologic signs (seizures) with food 
hypersensitivity. • Respiratory signs have 
been reported in dogs.
• Dogs—rump, perineum, axillae, groin, 
face, and interdigital areas frequently 
affected. • Cats—face, neck, and ears 
frequently affected. • Cats—lesions of the 
eosinophilic granuloma complex. • Otitis 
externa. • Malassezia dermatitis. 
• Secondary bacterial folliculitis. 
• Plaques. • Pustules. • Erythema. 
• Crusts. • Scale. • Self-induced alopecia. 
• Excoriation. • Lichenification. 
• Hyperpigmentation. • Urticaria. 
• Angioedema. • Pyotraumatic dermatitis. 
• Acral lick dermatitis.
CAUSES
• Immune-mediated reactions (food hypersen -
sitivity)—result from the ingestion and 
subsequent presentation to the immune system 
of one or more glycoproteins (allergens) either 
before or after digestion; sensitization may 
occur at the gastrointestinal mucosa, after the 
substance is absorbed, or both; cross-reactivity 
between various food allergens, and between 
food and pollen allergens, has been demon -
strated. • Non-immune-mediated reactions 
(food intolerance)—result of ingestion of foods 
with high levels of histamine or substances that 
induce histamine either directly or through 
histamine-releasing factors.
• Unknown. • Intestinal parasites, 
infection, or inflammation may damage the 
intestinal mucosa, resulting in the abnor -
mal absorption of allergens and subsequent 
sensitization.
 DIAGNOSIS
• Flea bite hypersensitivity—usually confined 
to the caudal half of the body; often seasonal. • Atopy—similar clinical symptoms, but 
typically develop between 1 and 3 years of age; 
20–30% of dogs with adverse reactions to 
food also have atopic dermatitis. • Drug 
reactions—history of drug administration 
before the development of signs and improve -
ment after withdrawal of the suspected drug. 
• Scabies mites—pruritus usually specific to 
the ears, elbows, and hocks (dogs) and head, 
ears, and neck (cats); mites in skin scrapings 
and/or response to specific therapy.
N/A
In vitro (serum, hair, saliva) allergy tests; 
poor correlation between test results and 
food exposure; poor correlation between diet 
trial and test results; neither sensitive or 
specific; significant discrepancy between 
labs; currently no standard to enable 
comparisons between techniques; not 
recommended either as a diagnostic test for 
food allergy or for choosing appropriate 
ingredients for food trials.
Diagnosis requires response to dietary 
exclusion in the form of restricted-ingredient 
food trials followed by challenge and 
redevelopment of symptoms.
Food Elimination Diet
• Definitive test for adverse food reactions. 
• Tailored to the individual patient. • Diet 
must be restricted to one novel protein and one 
novel carbohydrate—veterinary prescription 
novel protein or hydrolyzed diets strongly 
recommended over over-the-counter novel 
protein diets; multiple studies report 
c ontamination of over-the-counter diets with 
proteins not listed on the label. • Most patients 
will improve within 6–8 weeks. • Food trials 
should be continued up to 10 weeks unless 
improvement occurs earlier. • Home-cooked 
food trials remove possible sources of antigen 
due to processing, storage, and cross-contami -
nation from other ingredients.
Challenge and Provocation Diet Trials
• Used if the patient improves on the 
elimination diet.
• Challenge—feed the patient the original 
diet; a return of the signs confirms that the 
original diet contains an inciting ingredient; 
the challenge period should last until the 
signs return, but no longer than 10 days. 
• Provoke (provocation diet trial)—if the 
challenge confirmed the presence of an 
adverse food reaction, add single ingredients 
to the elimination diet; test ingredients 
include a full range of meats (beef, chicken, 
fish, pork, lamb), a full range of 
c arbohydrates (corn, wheat, soybean, rice), 
eggs, and dairy products; the provocation 
period for each ingredient should last up to 
10 days or less if signs develop sooner; results Food Reactions, Dermatologic

Canine and Feline, Seventh Edition  541
F
Fguide the selection of commercial foods that 
do not contain the offending substance(s).
• Skin biopsy—not diagnostic; may be 
helpful to confirm or eliminate other 
differential diagnoses. • Histopathologic 
findings—variable; common findings suggest 
hypersensitivity; secondary bacterial folliculitis 
or Malassezia dermatitis may be present.
 TREATMENT
Avoidance of the offending food substance(s).
Outpatient management .
DIET
Avoid any food substances that caused the 
clinical signs to return during the provocation 
phase of the diagnosis.
• Explain the principles involved in each phase 
of the diagnostic test diets. • Instruct client to 
eliminate treats, chewable toys, vitamins, 
medication wraps, and flavored medications 
(e.g., parasiticides), as these may contain 
previously fed ingredients. • If a home-cooked 
diet is needed, the website www.balanceit.com 
is useful to create a diet with adequate 
supplementation. • Outdoor pets must be 
confined to prevent foraging and hunting. 
• Advise all family members to adhere to the 
restricted-ingredient diet trial protocol.
• Systemic antipruritic drugs—may be useful 
during the first 2–3 weeks of diet trial to 
control self-mutilation. • Antibiotics or 
antifungal medications—useful for secondary 
bacterial folliculitis or Malassezia dermatitis.
• Antibiotics that are known to have 
anti-inflammatory effects (e.g., tetracy -
cline, doxycycline, erythromycin, and trimethoprim-potentiated sulfas) may confuse 
response to dietary trials. • Chewable 
medications may contain a food protein such 
as chicken or beef to which the animal is 
allergic. • Glucocorticosteroids and 
antihistamines should be discontinued for at 
least 10–14 days while on the diet trial to allow 
correct assessment of the animal’s response.
N/A
None
None
 FOLLOW-UP
Examine patient and evaluate and document 
the pruritus and clinical signs every 3–4 weeks.
Avoid intake of any of the ingredients 
included in the previous diet, including treats 
and chewable vitamins and toys.
Other causes of pruritus, such as bacterial or 
yeast infections, as well as parasites such as 
fleas or mites, must be eliminated or 
controlled to permit accurate assessment of 
the effect of dietary antigens on clinical signs.
• Prognosis is good if food ingredients are the 
only cause of pruritus and offending ingredi -
ents are avoided. • Rarely a dog or cat may 
develop hypersensitivity to new substances, 
requiring a new elimination diet trial. • A 
partial response to a food elimination diet trial 
suggests a combined food reaction with atopy 
or with another cause of pruritus.
• Superficial bacterial folliculitis. • Malassezia 
dermatitis. • Otitis externa. • Atopic dermatitis.AGE-RELATED FACTORS
None, except age ranges during which 
symptoms of food allergy most often develop.
None
N/A
SYNONYMS
• Adverse reactions to food. • Food allergy. 
• Food hypersensitivity. • Food intolerance.
SEE ALSO
• Atopic Dermatitis. • Contact Dermatitis. 
• Malassezia Dermatitis. • Otitis Externa and 
Media. • Pyoderma.
Foster AP , Knowles TG, Moore AH, et al. 
Serum IgE and IgG responses to food 
antigens in normal and atopic dogs, and 
dogs with gastrointestinal disease. Vet 
Immunol Immunopathol 2003, 
92(3–4):113–124.
Hillier A, Griffin CE. The ACVD task force 
on canine atopic dermatitis (X): Is there a 
relationship between canine atopic 
dermatitis and cutaneous adverse food 
reactions? Vet Immunol Immunopathol 
2001, 81(3–4):227–231.
Olivry T, DeBoer DJ, Prélaud P , et al. 
International Task Force on Canine Atopic 
Dermatitis. Vet Dermatol 2006, 
17:223–235.
Olivry T, Mueller RS. Critically appraised 
topic on adverse food reactions of compan-
ion animals (3): prevalence of cutaneous 
adverse food reactions in dogs and cats. 
BMC Vet Res 2017, 13(1):51.
Verlinden A, Hesta M, Millet S, Janssens GP . 
Food allergy in dogs and cats: a review. Crit 
Rev Food Sci Nutr 2006, 46(3):259–273.
Author  David D. Duclos 
Resnick 
available online(continued)  Food Reactions, Dermatologic

542  Blackwell’s Five-Minute Veterinary Consult  
F BASICS
• Adverse food reactions encompass disorders 
with an immunologic (food allergy), non­
immunologic (food intolerance), and toxic 
basis (food intoxication). • Food allergy, food 
intolerance, and food intoxication may have 
similar signs, diagnostics, and treatments and 
may not be easily distinguishable.
• The pathogenesis of food allergy involves 
complex immunologic events—a leaky 
intestinal mucosal barrier, dysregulated 
immune responses, and loss of oral tolerance. 
Most food allergies are due to type 1 
hypersensitivity reactions. Major food 
allergens include milk, eggs, beef, chicken, and 
plant proteins from corn, wheat, and 
soybeans. • Food intolerance may be due to 
idiosyncratic reactions to dietary ingredients 
or additives, pharmacologic reactions to 
compounds in the diet, defects or deficiencies 
in the metabolic pathways needed to use the 
food, or a toxicity reaction to food ingredients 
or spoiled foodstuffs. Unlike food allergy, food 
intolerance requires no previous exposure to 
the food product. • Toxic reactions to food 
may occur when a foodstuff is ingested in 
large amounts (e.g., onion poisoning).  
• Toxicity reactions occur when food contains 
toxins (e.g., aflatoxin, a hepatotoxin produced 
by Aspergillus  spp.) or has spoiled or been 
contaminated by bacterial growth.
• Gastrointestinal (GI)—small intestine, 
colon, and/or stomach can be affected by 
adverse food reactions. • Skin/exocrine—food 
allergy can manifest with concurrent 
dermatologic signs or exclusive dermatologic 
signs.
GENETICS
Gluten sensitivity in Irish setters has a genetic 
basis.
Up to 50% of dogs and cats with chronic GI 
signs respond to an elimination diet.
N/A
Species
• Soft­coated wheaten terriers affected with 
the syndrome of protein ­losing enteropathy 
(PLE) and/or protein ­losing nephropathy 
(PLN) have been shown to be affected by 
food allergies, which may play a role in the 
development of PLE/PLN. • Gluten ­sensitive enteropathy is an autosomal recessive trait 
seen in some Irish setters.
• Dogs affected with diet ­responsive chronic 
enteropathy tend to be young (median age 3.4 
years in one study). • Cats of all ages have been 
reported to be affected (median age 5 years).
None
SIGNS
• Food intolerance commonly produces 
diarrhea (small or large bowel), vomiting, 
flatulence, anorexia, and abdominal 
d iscomfort. • Food allergy may cause 
cutaneous signs, such as pruritus and hair 
loss, which may be associated with GI signs.
• Acute food intolerance may accompany 
feeding a novel foodstuff, a new food source, 
or dietary change. • Clients may report 
cessation of clinical signs in the fasted state or 
within days of an elimination diet trial.
The physical examination is generally 
nonspecific, but may show abdominal 
discomfort, flatulence, bloating, or patchy 
areas of alopecia along the pinnae of the ears 
and periorbital regions, especially in cats.
CAUSES
• Idiosyncratic reactions to food a  dditives—
colorings, preservatives (butylated hydroxyani ­
sole, monosodium glutamate, sodium nitrate, 
sulfur dioxide, etc.), spices, propylene glycol, 
etc. • Pharmacologic reactions—v  asoactive 
substances (i.e., histamine), psychoactive 
agents, stimulants (i.e., theobromine, caffeine), 
etc. • Metabolic defects or deficiencies—brush 
border enzyme defects (i.e., lactase deficiency), 
inborn errors of metabolism, aminopeptidase N 
(in gluten ­sensitive enteropathy). • Toxic 
reactions to foods or spoiled foods—spices, 
oxalate toxicity, lectin toxicity, N­propyl 
disulfide a  flatoxicosis, ergotism, botulism, 
dietary i  ndiscretion, etc. • Genetic mutations in 
innate immunity genes regulating host 
responses to dietary constituents.
• Young Irish setters susceptible to gluten ­sensi­
tive enteropathy may be at greater risk of 
developing the disease if exposed to gluten at an 
early age. • Host genetic susceptibility is suspected 
in wheaten terriers and German shepherd dogs.
 DIAGNOSIS
• Infectious diseases—intestinal nematodes, 
Giardia , histoplasmosis, salmonellosis, toxoplasmosis (cats), feline infectious 
peritonitis. • Infiltrative GI diseases—
i nflammatory bowel disease, histiocytic 
ulcerative colitis (boxers, French bulldogs).  
• Endocrine diseases—h  ypoadrenocorticism, 
hyperthyroidism (cats). • Exocrine pancreatic 
insufficiency. • Lymphangiectasia. • GI 
motility disorders. • Pancreatitis.  
• Metabolic diseases (renal disease, liver 
disease).
Usually normal; animals with food allergy 
may occasionally have eosinophilia.
• Few diagnostic tests are specific to adverse 
food reactions, but the following are helpful 
to rule out differential diagnoses and to identify 
complicating factors. • Serum cobalamin and 
folate—can help determine involvement of 
proximal and distal small intestine as well as 
identify possible need for supplementation. 
• T rypsin ­like immunoreactivity—for exocrine 
pancreatic insufficiency. • Baseline cortisol or 
adrenocorticotropic hormone stimulation 
test—to rule out hypoadrenocorticism if 
clinically suspected. • Total T4 (cats)—to 
evaluate for h  yper thyroidism if clinically 
suspected. • Fecal alpha ­1 proteinase 
inhibitor—this test can be performed if there 
is a suspicion of PLE, but other lab results are 
equivocal, or there is complicating proteinuria. 
• Perinuclear antineutrophilic cytoplasmic 
autoantibodies—this test is currently limited 
to use in a research setting, but has shown 
promise in early detection of PLE and PLN, 
believed to be due to underlying food allergy, 
in soft ­coated wheaten terriers. Additionally, 
it may help to differentiate between dogs with 
diet­responsive enteropathies and enteropathies 
requiring treatment with g  lucocorticoids. 
• Fecal flotation and fecal smear—perform 
2–3 tests over several days to increase 
sensitivity. • Empiric deworming with a 
broad ­spectrum anthelminthic may be 
considered to address possible undetected 
IMAGING
• Abdominal radiographs or ultrasound 
may be useful in eliminating differential 
diagnoses. • Doppler evaluation (ultra ­
sound) may detect alterations in blood flow 
through the celiac and cranial mesenteric 
arteries of dogs.
• Perform an elimination diet trial of 2 weeks 
in cats and 3 weeks in dogs with GI signs.  
• Following improvement on an elimination 
diet, use challenge exposure to sequential 
single ingredients to specifically identify the 
incriminating dietary ingredient. While 
technically the gold standard, this is 
generally impractical in a clinical setting.  Food Reactions (Gastrointestinal), Adverse

Canine and Feline, Seventh Edition  543
F• Exclusive feeding with a hydrolyzed or novel 
protein source indefinitely is generally 
required to prevent clinical relapse. • Perform 
urinalysis and urine protein : creatinine ratio 
(if indicated) in diet ­responsive wheaten 
terriers to screen for concurrent glomerular 
injury with urinary protein loss.
Villous atrophy and mild lymphoplasmacytic 
enteritis may be seen with food allergy.
 TREATMENT
Generally treat on an outpatient basis.
If an adverse food reaction is severe, IV fluid 
therapy, administration of antiemetics, and 
nutritional support via enteral ­assisted 
feeding may be temporarily required.
ACTIVITY
DIET
• Lifelong dietary management is essential 
for animals with food intolerance and food 
allergy. • Diets that can be chosen for an 
elimination diet trial include veterinary 
prescription hydrolyzed protein diets, 
commercial novel protein diets (available 
as veterinary prescription diets or over ­t he­
counter products), or a home ­cooked novel 
protein diet. • Novel protein diets are 
foods containing only protein sources to 
which the animal has not been previously 
exposed and are selected based on a careful 
dietary history. • Over ­the­counter novel 
protein diets have been found to contain 
proteins other than those listed on the 
label, which may be due to contamination 
during processing; veterinary prescription 
products are prepared specifically for animals 
with food allergy and should be chosen 
when possible. • Home ­prepared novel 
protein diets can uncommonly result in a 
beneficial response in animals who did not 
respond to a commercial diet containing the 
same protein. Considerations for home ­
prepared novel protein diets are that many 
are not suitable for long ­term feeding 
(unless the diet is complete and balanced 
with the help of a veterinary nutritionist) and create inconvenience for the owner, 
which may limit compliance. • Hydrolyzed 
protein diets are created by enzymatic 
hydrolysis of the intact protein into 
peptides small enough to reduce the 
potential of the protein to induce an 
allergic response. • Hydrolyzed diets are 
ideal when an animal has been exposed to 
many different protein sources or when a 
reliable dietary history cannot be obtained.  
• Hydrolyzed protein diets can retain some 
antigenicity and, if possible, the parent 
protein of the hydrolyzed diet should be a 
protein to which the animal does not have a 
known sensitivity. • Hydrolyzed protein diets 
may also benefit animals without true food 
allergy due to the improved d  igestibility of 
the diet.
• Owners should be aware of possible sources 
of food antigen during an elimination trial 
that may make the animal’s response difficult 
to interpret, including table scraps, flavored 
medications and toothpastes, and coprophagy. 
• Counsel clients on the necessity of lifelong 
avoidance of ingredients to which their 
animal is sensitive.
N/A
N/A
 FOLLOW-UP
• Assess efficacy of elimination diet trial by 
observing improvement in GI signs.  
• Failure to improve in 2–3 weeks may 
warrant a subsequent trial with another diet 
if adverse food reaction is strongly s  uspected, 
or continued work ­up for other causes of GI 
signs, including endoscopy with biopsies.
PREVENTION AND AVOIDANCE
Avoid foods, treats, and flavored medications 
outside of the elimination diet.
The prognosis is excellent as long as the 
offending dietary components are successfully 
identified and avoided.
N/A
N/A
None
N/A
SYNONYMS
• Food intolerance. • Food allergy. • Dietary 
sensitivity. • Food ­responsive enteropathy.
SEE ALSO
• Gluten Enteropathy in Irish Setters.
https://www.vin.com/VIN.plx
Gaschen FP , Merchant SR. Adverse food 
reactions in dogs and cats. Vet Clin North 
Am Small Anim Pract 2011, 
41(2):361–379.
Guilford WG. Food sensitivity in cats with 
chronic idiopathic gastrointestinal 
problems. J Vet Intern Med 2001, 15:7–13.
Roudebush P . Ingredients and foods 
associated with adverse reactions in dogs 
and cats. Vet Dermatol 2013, 
24(2):293–294.
Author  Albert E. Jergens 
available online(continued)  Food Reactions (Gastrointestinal), Adverse

G
544  Blackwell’s Five-Minute Veterinary Consult  
GGallbladder Mucocele
  BASICS
OVERVIEW
• Gallbladder (GB) accumulation of 
tenacious, thick, mucin-rich, inspissated bile 
conglomerate (sludge) impairing GB reservoir 
capacity and GB contraction, thereby 
thwarting periprandial bile expulsion; often 
associated with episodic abdominal pain. 
• Organized sludge expands GB lumen, 
flattens/thins GB wall; when severe, provokes 
necrotizing cholecystitis and occasional GB 
rupture. • Canine syndrome, rare in cats. 
• Initiated by GB dysmotility.
• Dog. • Shetland sheepdogs, miniature 
schnauzers, cocker spaniels, bichon frisé, 
shih tzu overrepresented in one study of 
219 dogs. • Middle-aged to older adults. 
• No sex predilection. • Associated with 
endocrinopathies—adrenal hyperplasia 
(typical or sex hormone atypical form), 
hypothyroidism, diabetes mellitus, and 
administration of glucocorticoids; these 
likely associated with GB dysmotility, 
hypertriglyceridemia, or hypercholesterolemia 
that may impart negative influence on GB 
contraction. • Notably associated with 
hypertriglyceridemic syndromes.
SIGNS
• Symptomatic or asymptomatic—depending 
on stage at diagnosis: mature vs. immature gall 
bladder mucocele (GBM). • Asymptomatic 
GBM—often serendipitously discovered on 
abdominal US.
Historical Findings: Symptomatic
• Episodic periprandial abdominal 
discomfort. • Anorexia. • Vomiting. 
• Lethargy. • ± Polyuria/polydipsia—reflects 
underlying endocrinopathy. • Collapse—
vasovagal episode or bile peritonitis.
• May demonstrate no physical signs if 
immature GBM. • ± Lethargy. • ± Cranial 
abdominal discomfort—GB dysmotility and 
maturing GBM. • Jaundice late in syndrome. 
• ± Dehydration. • ± Fever—secondary 
• Inborn errors of lipid metabolism 
(hypertriglyceridemia)—miniature schnauzer, 
Shetland sheepdogs, beagles, others. 
• Medical/dietary conditions provoking 
hypercholesterolemia or dyslipidemia—
endocrinopathies, recurrent pancreatitis, 
feeding high-fat diet to dog with predisposing 
disorder or dyslipidemia. • GB dysmotility. 
• Cystic mucosal hyperplasia—common in 
older dogs; may be aggravated by sex 
hormones (e.g., progestins).  DIAGNOSIS
Conditions causing GB bile stasis—GB 
dysmotility; or other causes of incomplete GB 
emptying such as cystic duct or GB wall 
neoplasia, pedunculated adenomatous mucosal 
lesions, ball-valve cholelith obstructions.
CBC
• Inflammatory leukogram—variable, 
depends on GB wall viability and hepatic 
impact of GBM. • Stress leukogram—if 
underlying hyperadrenocorticism. 
• Nonregenerative anemia—if chronic 
inflammation or hypothyroidism.
• High liver enzymes—may be noted on acute 
presentation for GBM or serendipitously 
discovered on routine health assessments; 
alkaline phosphatase (ALP), γ-glutamyl -
transferase (GGT), alanine aminotransferase 
(ALT), ± aspartate aminotransferase (AST) 
variably affected; ALP activity predominant. 
• High ALP—often associates with glycogen-
type vacuolar hepatopathy (VH), may reflect 
adrenal endocrinopathy or glucocorticoid 
therapy. • Variable hyperbilirubinemia; 
depends on GBM maturation and common 
bile duct patency. • Low albumin—if 
ruptured biliary tree and bile peritonitis. 
• Prerenal azotemia—if ruptured GB, sepsis, 
or dehydration from vomiting. • Electrolyte 
abnormalities with fluid and acid-base 
disturbances—due to bile peritonitis or 
persistent vomiting.
No specific features.
• T riglyceride concentrations.
• Coagulation tests—normal unless chronic 
extrahepatic bile duct obstruction (EHBDO), 
GB rupture, bile peritonitis, sepsis, or 
disseminated intravascular coagulation (DIC).
IMAGING
• Abdominal radiography—normal or large 
liver; loss of detail in cranial abdomen if focal 
peritonitis with GB rupture or concurrent 
pancreatitis; rarely intrahepatic gas. • Abdominal 
US—liver may be large, with rounded margins, 
or normal sized; diffuse to multifocal 
hyperechoic hepatic parenchyma (associated 
with glycogen-type VH); may have hypoechoic 
nodular appearance if severe VH; typical GBM 
US image: lumen filled with amorphous 
echogenic “organizing” nongravitational debris 
with stellate or finely striated pattern resembling 
sliced kiwi fruit (“kiwi sign”); distended GB 
(>1.2 mL/kg bodyweight) and sometimes 
distended common bile duct ± cystic duct if 
EHBDO; pericholecystic edema may enhance GB wall imaging; pericholecystic or generalized 
effusion with hyperechogenicity of surrounding 
tissues may indicate focal peritonitis and bile 
leakage (even if GB wall not ruptured); diffusely 
thick GB wall with segmental hyperechogenicity 
and double-rimmed or laminated appearance 
associates with necrotizing cholecystitis; GB 
rupture associated with discontinuous GB wall 
or difficult-to-image GB; ruptured GBM may 
have inspissated congealed biliary material 
released into abdominal cavity where discrete 
free-floating “mass” may be discovered; 
intrahepatic bile ducts may be difficult to 
visualize or appear prominent or distended. 
• GB motility study—indicated if suspected 
developing GBM serendipitously recognized if 
GB volume ≥1.2 mL/kg bodyweight; sequential 
GB volume measurements determined after 
meal ingestion (100 g food; may include 0.5 mg/
kg erythromycin as motilin agonist provoking 
GB contraction if no response with food alone). 
Normal GB contraction results in ≥25% decline 
of initial or baseline GB volume on one or more 
recorded postprandial images. Procedure: image 
GB at 0, 15, 30, 45, 60, 90, 120 min relative to 
feeding. • GB volume in mL = [length (cm) × 
width (cm) × height (cm)] × 0.52.
• Aspiration sampling—fluid adjacent to 
biliary structures or free in abdominal cavity; 
clarifies GB rupture and/or infection; caution : 
do not perform cholecystocentesis on suspected 
GBM as this may cause bile peritonitis. 
• Laparotomy—for diagnosis, cholecystectomy, 
perhaps cholecystenterostomy. 
• Laparoscopy— not advised as CBD should be 
flushed to patency. • Liver biopsy—collect 
biopsy distant to GB; biopsy from GB area 
often interpreted as severely fibrotic or as 
cholangitis. • Bacterial culture/sensitivity—any 
effusion; GB wall, mucinous debris clinging to 
GB wall (scrape GB wall for best sample), liver 
(single inoculum); request aerobic and 
anaerobic bacterial culture. Positive ranging 
from 17% to 33% in different studies; 
histologic identification of bacteria unreliable. 
• Cytology—impression smears of GB wall 
mucinous debris and liver assist prompt 
recognition of suppurative septic inflammation 
or rarely neoplasia.
• Gross—mature GBM: GB distended, wall 
may appear normal, erythematous, or 
hemorrhagic ± focal areas of necrosis; may be 
evidence of focal peritonitis with adhesions; 
liver and extrahepatic biliary structures usually 
appear normal but EHBDO possible; GB 
contents: dark green-black, tenacious, firm, or 
organized as solid light green-yellow rubbery 
conglomerate. Slender long proliferative 
mucosal projections or cystic mucosal 
hyperplasia on GB mucosa are common. 
Immature GBM: normal to distended GB 
with thick dark black green bile with black

with thick dark black green bile with black 
particulate calcium bilirubinate debris.

Canine and Feline, Seventh Edition  545
GG• Microscopic—mature GBM demonstrates 
mural thinning with elongate mucosal fronds 
± cystic mucosal hyperplasia and laminated 
dehydrated mucin; occasional particulate 
bilirubinate conglomerates in GB sections; 
mixed inflammatory infiltrates and fibrosis in 
chronic GBM; focal areas of necrosis usually 
caused by arterial thrombosis; Gram stain and 
modified Steiner’s stains should be used to 
detect intraluminal bacteria as not all cultures 
recover infectious organisms. If GB not 
sectioned before fixation, mucosa may not fix 
and will appear necrotic. Liver biopsy 
collected distant to GB often discloses 
glycogen-type VH with no evidence of 
mechanical bile stasis if immature GBM and 
underling endocrinopathy; ascending 
suppurative cholangitis and cholangiohepatitis 
may be secondary complications.
  TREATMENT
• Outpatient management—ursodeoxycholic 
acid and S-adenosylmethionine (SAMe) 
induce bile acid and non-bile acid mediated 
choleresis and provide hepatoprotection— but 
medical therapy is not advised to resolve GBM. 
While medical management has occasionally 
resolved immature GBM in some dogs, these 
patients remain at risk for GBM recurrence. 
Naïve unmonitored treatment with choleretics 
may eventuate in ruptured GB. • Inpatient—
depends on whether patient presents with 
severe acute necrotizing cholecystitis, 
suppurative cholecystitis, intact nonurgent 
mature GBM, or incidentally discovered 
immature GBM. • If patient hyperlipidemic, 
investigate cause, restrict dietary fat, avoid 
glucocorticoids. • Symptomatic patients 
require exploratory surgery for 
cholecystectomy and evaluation/treatment for 
potential bile peritonitis. • Cholecystotomy 
and mucocele removal with GB retention not 
advised; high risk for recurrent GBM and 
potential bile peritonitis. • Fluid therapy—
balanced polyionic solutions to correct 
hydration and electrolyte status. • Be 
prepared for blood component therapy. 
• Abdominal lavage—at surgery if bile 
peritonitis encountered.
Antimicrobials
Initiate combined broad-spectrum antimicrobials 
before  surgery; continue treatment 4–8 weeks if septic complications; adjust drugs based on 
culture and sensitivity test reports and 
biochemical appraisals. If no histologic or culture 
evidence of infection and postoperative recovery 
unremarkable, discontinue antimicrobials 7–10 
days after surgery.
Vitamin K1
0.5–1.5 mg/kg IM/SC q12h for three doses—  
if jaundiced ; oral route ineffective if EHBDO.
Antiemetics/Antacids/Gastroprotectants
• Antiemetics—may be needed during 
preoperative interval. Maropitant citrate 
(Cerenia®), NK-1 antagonist—2 mg/kg PO 
or 1 mg SC q24h up to 5 days. Ondansetron—  
0.1–0.3 mg/kg PO 30 min before feeding, 
maximum q8h, or 0.1–0.2 mg/kg slow IV 
push q6–12h if vomiting. • Antacids—
preoperative interval, proton pump inhibitors 
preferred: omeprazole 0.7–1.0 mg/kg PO/IV 
q24h or pantoprazole 0.7–1.0 mg/kg IV 
q24h. • Gastric prokinetics—if postoperative 
gastric atony: metoclopramide 0.2–0.5 mg/kg 
PO/IV/SC q6–8h or 1–2 mg/kg/day CRI. 
• Gastroprotectant—if suspected gastritis, 
esophagitis, or upper gastrointestinal 
bleeding: sucralfate—0.5–1.0 g PO q8–12h.
Choleretics
• Maintain hydration status to optimize 
choleresis. • Ursodeoxycholic acid—choleretic, 
hepatoprotectant, anti-inflammatory, 
anti-endotoxic effects: 10–15 mg/kg PO 
divided BID daily with food for best 
bioavailability; treat until complete 
biochemical recovery or chronically if suspect 
persistent cholangitis. • SAMe—choleretic, 
antioxidant, and metabolic benefits; choleretic 
dose (40 mg/kg PO q24h on empty stomach) 
higher than antioxidant dose.
• Vitamin E— α-tocopherol 10 IU/kg/day 
PO with food: antioxidant, anti-
inflammatory, antifibrotic influence. 
• SAMe—20 mg/kg PO daily 2h before 
feeding: give until liver enzymes normalize or 
indefinitely if chronic hepatitis or cholangitis.
N/A
  FOLLOW-UP
• Repeat sequential hematology, 
biochemistry, and imaging to monitor 
surgical recovery; if GBM caused 
clinicopathologic abnormalities, all changes should resolve within weeks. • Persistent 
clinicopathologic abnormalities implicate 
underlying endocrinopathy, intrahepatic 
cholangiopathy, or other liver disease. 
• At-risk dogs should have US assessment of 
GB as part of routine health appraisal when 
middle-aged to geriatric.
• Suppurative cholangitis or cholangio -
hepatitis. • Bile peritonitis. • EHBDO.
• Good with successful surgery, chronic 
choleretic therapy, correction/management of 
comorbid conditions, dietary and/or medical 
management of hypertriglyceridemia. 
• Anticipate protracted clinical course if 
ruptured biliary tract or peritonitis—dogs 
with ruptured GBM 2–3 times more likely to 
succumb to GBM-related illness. 
• Recrudescence may occur if mucocele 
contents removed and GB retained, with or 
without chronic medical therapy. • Chronic 
postoperative jaundice may reflect iatrogenic 
stricture at site of cholecystectomy.
SEE ALSO
• Glycogen-Type Vacuolar Hepatopathy.
• EHBDO = extrahepatic bile duct obstruction.
• GGT = γ–glutamyltransferase.
• VH = vacuolar hepatopathy.
Aguirre AL, Center SA, Randolph JF . 
Gallbladder disease in Shetland Sheepdogs: 
38 cases (1995–2005). J Am Vet Med Assoc 
2007, 231:79–88.
Jaffey JA, Graham A, VanEerde E, et al. 
Gallbladder mucocele: variables associated 
with outcome and the utility of 
ultrasonography to identify gallbladder 
rupture in 219 dogs (2007–2016). J Vet 
Intern Med 2018, 32:195–200.
Consulting Editor  Kate Holan(continued)  Gallbladder Mucocele

G546  Blackwell’s Five-Minute Veterinary Consult  
GGastric Dilation and Volvulus Syndrome
  DEFINITION
Gastric dilation and volvulus syndrome 
(GDV) is a disease in which the stomach 
rotates around its short axis, with or without 
distention of the stomach.
The mechanism and etiology are poorly 
understood. Many risk factors have been 
evaluated. Rotation of the stomach can occur 
in any direction, but the majority occur in 
clockwise rotation. The pylorus, pyloric 
antrum, and proximal duodenum move from 
dorsal to ventral, from right to left of the 
patient, continuing from the ventral abdomen 
to the left, and eventually are located in the 
left dorsal quadrant of the peritoneal cavity. 
With distention of the stomach, intra-
abdominal pressure increases. Collapse of the 
compliant abdominal venous network leads 
to decreased venous return to the heart and 
portal hypertension. As the disease progresses, 
hypovolemic shock and decreased organ 
perfusion lead to local and systemic 
inflammatory response, visceral and 
myocardial ischemia, disseminated 
intravascular coagulation (DIC), and 
eventually cardiovascular collapse and death.
• Gastrointestinal (GI)—rotation of the 
stomach causes venous congestion of the 
stomach, spleen, pancreas, and proximal small 
intestine and arterial compromise of the 
stomach. • Hemic/lymphatic/immune—splenic 
engorgement, vascular compromise, ischemia, 
and thrombosis are common. 
• Cardiovascular—both distributive and 
obstructive hypovolemic shock may be seen; 
cardiac arrhythmias are common. • Renal/
urologic—acute kidney injury (AKI) may occur 
secondary to shock and renal vascular 
compression. • Endocrine/metabolic—
nephrogenic diabetes insipidus has been 
reported, likely secondary to AKI, endotoxemia, 
and systemic inflammatory responses.
GENETICS
• Having a first-order relative with a history 
of GDV markedly increases the risk of 
developing GDV. • While the genetic basis is 
unknown, it is likely to be a complex, 
multifactorial (or polygenic) disorder.
One study indicated that likelihood of a 
purebred large- or giant-breed dog developing 
GDV during its lifetime is approximately 
24% and 21.6%, respectively.
N/A
Species
Dog (common) and cat (rare).Breed Predilections
• German shepherd dog. • Great Dane. 
• Standard poodle. • Labrador retriever. 
• Akita. • Golden retriever. • Saint Bernard. 
• Doberman pinscher. • Chow chow. • Collie. 
• Rottweiler. • Mastiff. • Weimaraner. 
• Bloodhound. • Basset hound. • Belgian 
shepherd. • Great Pyrenees. • Boxer. • Husky. 
• German shorthaired pointer. • Samoyed. 
• Newfoundland. • Bernese mountain dog. 
• Smaller breeds are reported, including 
dachshund, corgi, and Pekingese.
Any age. Risk increases with age in large- and 
giant-breed dogs.
Male > female.
SIGNS
• Restlessness. • Anxiety. • Vomiting 
progressing to nonproductive retching or 
nonproductive retching alone. • Abdominal 
distension and/or pain. • Ptyalism. 
• Lethargy. • Collapse.
• Distended abdomen; may not be noted in 
deep-chested dogs. • Tachycardia. 
• Tachypnea or dyspnea. • Weak pulses. 
• Pale or hyperemic mucus membranes and 
prolonged or rapid capillary refill time.
CAUSES
• Multifactorial. • Genetic. • Conformational. 
• Environmental. • Secondary to gastric, 
hepatic, or splenic neoplasia. • Any cause of 
aerophagia. • Massive food consumption or 
other cause of gas or liquid gastric distention. 
• Pyloric outflow obstruction.
• Direct relative with a history of GDV. 
• Large- or giant-breed dog. • Deep-chested 
body conformation. • History of splenic torsion, 
colonic torsion, or mesenteric volvulus. • Gastric 
motility disorder. • Rapid consumption of large 
amounts of food and water with or without 
excessive postprandial activity. • Altered 
microbiome. • T rauma. • Anxious temperament.
  DIAGNOSIS
• Gastric dilation without volvulus. 
• Abdominal effusion. • Any cause of 
abdominal pain. • Gastric or intestinal 
obstruction. • Urinary tract obstruction. 
• Pyometra. • Splenic torsion. • Mesenteric 
volvulus. • Colonic torsion. • Hepatic, 
gastric, or splenic mass.
• Stress leukogram; hemoconcentration; 
thrombocytopenia from consumption if DIC is present or if significant intra-abdominal 
hemorrhage has occurred. • Electrolyte 
abnormalities; increased liver enzymes; 
azotemia, either prerenal or due to AKI. 
• Increased specific gravity with dehydration; 
isosthenuria with AKI.
• Plasma lactate—initial lactate and trends 
are useful in predicting gastric necrosis and 
prognosis. ◦ Dogs with initial lactate 
>9 mmol/L had reduced survival (13/24 = 
54%) compared to those with initial lactate 
≤9 mmol/L (36/40 = 90%). ◦ Dogs with 
initial lactate >9 mmol/L that did not 
decrease by ≥4 mmol/L had 10% survival 
rate, while those whose lactate decreased by 
≥4 mmol/L with presurgical stabilization had 
90% survival rate. ◦ Decrease in plasma 
lactate by ≥50% within 12 hours is associated 
with a good outcome. • Coagulation 
testing—may show evidence for DIC.
IMAGING
• Abdominal radiography—right lateral 
abdominal radiograph is imaging modality of 
choice. ◦ In a normal patient, the pylorus 
would be filled with fluid. ◦ In a patient with 
GDV, the pylorus, which is now on the left 
side of the peritoneal cavity, is filled with gas 
and visualized as such, showing the classic 
compartmentalization of the stomach, which 
is considered to be pathognomonic. ◦ Gas 
bubbles within the gastric wall indicate gastric 
necrosis. ◦ Pneumoperitoneum may be 
evident. • Thoracic radiographs—three views 
to screen for aspiration pneumonia and 
metastatic disease; may also see evidence of 
hypovolemia (microcardia, small-caliber 
vessels). • Abdominal ultrasound—may show 
fluid due to small volume hemoabdomen, 
serosanguinous effusion, or gastric perforation.
ECG to detect presence of cardiac 
• Splenic engorgement, ischemia, 
malposition, and/or venous thrombosis. 
• Gastric wall may appear edematous and 
thickened, or areas may be extremely thinned.
  TREATMENT
• GDV is a medical and surgical emergency. 
• Aggressive emergency medical stabilization 
is initiated. • Subsequent to cardiovascular 
stabilization, gastric decompression should be 
performed, ideally via orogastric intubation; 
the patient should be intubated with a cuffed 
endotracheal tube prior to performing 
orogastric intubation and decompression 
to minimize the risk of aspiration pneumonia. 
• If orogastric intubation is unsuccessful,

Canine and Feline, Seventh Edition  547
GGpercutaneous gastrocentesis may be 
performed for decompression by locating the 
point of maximal tympany, which typically 
corresponds to an area of the stomach that is 
gas filled. ◦ The largest-diameter needle or 
catheter that the clinician is comfortable 
using is passed into the stomach at this area. 
◦ Considerable time is necessary to achieve 
gastric decompression using this technique. 
• Recent studies suggest that when comparing 
orogastric decompression and percutaneous 
decompression, there is no difference in 
complication rates or outcome. Therefore, 
clinicians should select the technique that they 
are most familiar and comfortable with. 
• Surgical management occurs once the 
patient is stable.
• IV fluid therapy is initiated and type, rate, 
and duration are based on individual patient 
needs and personal preference. ◦ Avoid use of 
saphenous veins for emergency resuscitation, 
as venous return from the caudal half of the 
body is compromised. ◦ Crystalloids, 
colloids, or a combination can be used; initial 
fluid resuscitation efforts may require 
crystalloid boluses at 15–30 mL/kg 
increments, up to 90 mL/kg total; colloid 
boluses up to 5–10 mL/kg total may be 
required. • Physical therapy may be necessary, 
as many patients will be recumbent for several 
days in the postoperative period.
ACTIVITY
Restriction of activity for 2 weeks 
postoperatively is recommended.
DIET
• Enteral nutrition is recommended as soon 
as adequate recovery from anesthesia has been 
achieved to stimulate GI mucosal healing and 
motility. • Optimal diet is unknown; consider 
fat-restricted diets to improve gastric 
emptying.
• Clients should be aware of the critical 
nature of GDV. • Patients can still experience 
gastric dilation after gastropexy, as many have 
gastric motility disorders.
• Surgery is required after medical 
stabilization. • Goals of surgery are: 
◦ Continue decompression. ◦ Assess stomach 
and spleen for evidence of devitalization and 
necrosis that necessitates partial gastrectomy 
or splenectomy. ◦ Reposition stomach and 
spleen. ◦ Perform systematic and thorough 
exploratory laparotomy. ◦ Perform gastropexy 
to prevent recurrence of GDV—should 
always be performed; decreases risk of 
recurrent GDV from 80% to <5%; 
incorporating gastropexy and gastrocolopexy 
are associated with higher rates of recurrence 
of GDV and should not be performed.  MEDICATIONS
• Lidocaine beginning with a 2 mg/kg IV bolus, 
followed by a CRI (0.05 mg/kg/min for 24h) in 
perioperative period improves morbidity but not 
mortality. ◦ Fewer cardiac arrhythmias. ◦ Lower 
incidence of AKI. ◦ Shorter hospitalization. 
• Perioperative antibiotics are indicated. ◦ For 
patients with moderate to severe disease in which 
there is a risk of visceral perforation or 
hematogenous bacterial translocation from the 
GI tract, cefoxitin sodium (30 mg/kg IV q6–8h) 
may be an appropriate choice. ◦ For patients in 
which no entry into the GI tract has occurred, 
cefazolin sodium (22 mg/kg IVq2h intra -
operatively) is sufficient. • T reatment for 
esophagitis and gastritis or gastric ulceration is 
indicated. ◦ Pantoprazole (1 mg/kg IV q12h) or 
omeprazole (1 mg/kg PO q12h) for acid 
suppression. ◦ Metoclopramide (2 mg/kg/day 
IV as CRI) or cisapride (0.5–1 mg/kg PO 
q8–12h) as a prokinetic. ◦ Sucralfate 0.25–1 g 
PO as a slurry q6–8h if gastric ulceration is 
present. • Pain management based on patient 
needs postoperatively.
Synthetic colloids should be used cautiously 
in patients with DIC or AKI.
Patients may decompensate at any time, 
particularly under anesthetic intervention. 
Emergency drug dosages should be calculated 
for the patient before anesthesia and be 
N/A
There is conflicting evidence to support the 
use of physiologic corticosteroids in patients 
with GDV. Use is not currently recommended.
  FOLLOW-UP
• Intermittent or continuous ECG 
postoperatively to monitor for arrhythmias. 
• Monitor urine production and renal 
function postoperatively.
While not proven, the following have been 
suggested to decrease risk of GDV: elevation 
of food bowl; avoiding exercise after eating or 
drinking; slowing rate of consumption of 
meals; feeding multiple smaller meals.
• Gastric dilation without volvulus may recur, 
even after a gastropexy is performed, because of a possible underlying motility disorder. 
• Failure to resect all necrotic or devitalized 
gastric tissue may result in eventual stomach 
perforation and septic peritonitis. • Cardiac 
arrhythmias, DIC, esophagitis, AKI, and 
gastric ulceration may also occur.
• Prognosis in dogs treated appropriately that 
do not have gastric necrosis is excellent, with 
a reported survival rate of 98%. • Dogs with 
gastric necrosis have a more guarded 
prognosis, with a reported survival rate of 
66%. • Potential negative prognostic 
indicators include hypotension, DIC, 
peritonitis, and the need to perform both a 
splenectomy and a partial gastrectomy.
N/A
More common in middle-aged to older dogs.
None
Affected dogs should not be bred due to 
potential genetic predisposition.
SYNONYMS
• Bloat. • Gastric torsion. • Gastric volvulus.
• AKI = acute kidney injury. • DIC = 
• GDV = gastric dilation and volvulus 
syndrome. • GI = gastrointestinal.
Allen P , Paul A. Gastropexy for prevention of 
gastric dilation-volvulus in dogs: history and 
techniques. Top Companion Anim Med. 
2014, 29:77–80.
Beck JJ, Staatz AJ, Pelsue DH, et al. Risk 
factors associated with short-term outcome 
and development of perioperative 
complications in dogs undergoing surgery 
because of gastric dilatation-volvulus: 166 
cases (1992–2003). J Am Vet Med Assoc 
2006, 229:1934–1939.
Zacher LA, Berg J, Shaw SP , Kudej RK. 
Association between outcome and changes 
in plasma lactate concentration during 
pre-surgical treatment in dogs with gastric 
dilation-volvulus: 64 cases (2004–2009). J 
Am Vet Med Assoc 2010, 236:892–897.
Author  Stephen Mehler
available online(continued)  Gastric Dilation and Volvulus Syndrome

G548  Blackwell’s Five-Minute Veterinary Consult  
G  BASICS
Gastric motility disorders result from 
conditions that disrupt normal peristalsis and, 
consequently, gastric emptying. This abnormal 
gastric retention may, in turn, cause gastric 
distention, and subsequent signs of anorexia, 
nausea, bloating, and vomiting.
The stomach has two distinct motor regions. 
The proximal stomach (fundus and body) 
relaxes to accommodate ingested food and 
regulates the expulsion of liquids. Intrinsic 
slow contractions of this region push liquids 
toward the pylorus. The distal stomach 
(antrum) mechanically breaks down solids 
through strong peristaltic contractions and 
ultimately expels them. The gastric pacemaker, 
an area of intrinsic electrical activity located 
in the greater curvature of the stomach, 
regulates distal gastric motility and emptying. 
Gastric electrical activity, dietary composition, 
and extrinsic factors (e.g., vagal and 
sympathetic innervation) all influence 
emptying. During fasting, indigestible solids 
are expelled from the stomach by migrating 
myoelectric complexes (MMCs). These 
produce strong “digestive housekeeper” 
contractions that, in the fasted state, sweep 
through the stomach and small intestine to 
mid-jejunum every 2 hours, preparing the 
gastrointestinal (GI) tract for the next meal. 
MMCs are regulated by the hormone motilin. 
Dysrhythmias in normal gastric electrical activity 
may be fundamental in the patho  physiology of 
disorders affecting gastric motility, but may 
also be secondary to gastric inflammation, 
neoplasia, and overdistension.
GI
GENETICS
N/A
Unknown. Many factors can alter gastric 
emptying, although they may not result in 
clinical disease or may only partially 
N/A
Species
Unknown
Signs occur at any age, though it is 
uncommon to observe primary motility 
disorders in young animals.
N/ASIGNS
Clinical signs are often secondary to the 
primary etiology causing the gastric motility 
disorder.
• Major clinical sign is chronic postprandial 
vomiting of food; stomach should normally be 
empty after average-sized meal in approx 6–8 
hours in dogs and 4–6 hours in cats (note: 
normal emptying times vary greatly from animal 
to animal and are influenced by meal volume, 
caloric density, fiber content, and environmental 
factors, e.g., stress); vomiting of undigested food 
>12 hours following meal suggests abnormal 
gastric motility or outflow obstruction; 
vomiting can occur, however, any time after 
eating. • Gastric distention, nausea, anorexia, 
belching, bloating, pica, and weight loss may 
occur. • Distal esophageal sphincter may be 
incompetent with gastric hypomotility and signs 
associated with reflux esophagitis may occur.
• Normal or findings associated with 
underlying cause. • Palpation of large, 
distended stomach. • Decreased gastric 
sounds on abdominal auscultation.
CAUSES
• Rarely, idiopathic gastric motility disorders 
arise from primary defects in normal myoelectric 
activity, e.g., myenteric ganglionitis, intestinal 
leiomyositis; most motility disorders occur 
secondary to other conditions. • Metabolic 
disorders include hypokalemia, uremia, hepatic 
encephalopathy, and hypothyroidism. • Nervous 
inhibition as result of stress, fear, pain, or trauma. 
• Drugs such as anticholinergics, beta-adrenergic 
agonists, narcotics, and chemotherapeutics. 
• Primary gastric disease such as outflow 
obstructions, gastritis, gastric ulcers, parvovirus, 
and gastric surgery. • Gastric dilatation and 
volvulus syndrome (GDV) is suspected to be, in 
part, result of abnormal gastric motility 
associated with changes in myoelectric and 
mechanical activity, although whether primary 
or secondary to overstretching of gastric wall is 
unknown; some dogs with GDV may continue 
to have signs of gastric hypomotility following 
surgical gastropexy. • Gastroesophageal reflux 
and enterogastric reflux (see Bilious Vomiting 
Syndrome) may result from primary gastric 
hypomotility. • Dysautonomia may affect GI 
tract and result in abnormal esophageal, gastric, 
and intestinal motility.
Any gastric disease may result in secondary 
hypomotility.
  DIAGNOSIS
Differential diagnosis is extensive and should 
consider any gastric condition causing vomiting, including gastritis, gastric ulcers, 
neoplasia, gastric surgery, and GDV. Gastric 
outflow obstruction as cause of delayed 
gastric emptying must always be ruled out.
Abnormalities may result from underlying cause 
of gastric hypomotility. Continued vomiting 
may result in changes indicative of dehydration, 
electrolyte abnormalities, or acid-base imbalance.
Specialized testing may be required to determine 
specific cause of gastric hypomotility, and is 
individualized for each patient.
IMAGING
Survey Radiographs
Abdominal radiographs may reveal gas-, fluid-, 
or ingesta-distended stomach. (Note: important 
to determine when patient was last fed in 
relationship to when radiographs were taken.)
Barium Contrast Study
May be evidence of delayed gastric emptying 
and decreased gastric contractions if evaluated 
using fluoroscopy. Some cases may have 
normal emptying of liquids but abnormal 
emptying of solids. Normal dogs should 
empty stomachs by approx. 6–8 hours. (Note: 
stress of radiographs may decrease gastric 
emptying even in normal animal.)
Ultrasound can evaluate antral and pyloric 
motility.
Tests Available in Specialized Practices
Radionuclide Emission Scintigraphy
Radionuclide markers mixed with a meal give 
most clinically accurate measurement of 
emptying. Gastric emptying times (time for 
standard meal to leave stomach) range from 4 
to 8 hours.
Stable Isotope Breath T ests
C-14-labeled foods are fed and time to onset 
of 14CO2 emission in breath is marker of 
gastric emptying.
Smartpill
This is noninvasive wireless sensor capsule 
that is given orally and transmits data on 
pressures, transit time, luminal pH, and 
temperature as it passes through stomach and 
small and large bowel. Has been validated for 
use in healthy dog but, as yet, limited reports 
evaluating clinical conditions.
Endoscopy
Endoscopic findings frequently normal in 
primary gastric motility disorders. Food may 
be found in stomach when it should be 
empty following 12-hour pre-endoscopic fast. 
Endoscopy will detect obstructive or 
inflammatory/ulcerative diseases of stomach.
• Idiopathic conditions have normal gastric 
mucosa; special staining may reveal disruption 
of enteric nervous system. • Gastric histology Gastric Motility Disorders

Canine and Feline, Seventh Edition  549
GGmay identify inflammatory or neoplastic 
causes of gastric hypomotility.
  TREATMENT
• Most treated as outpatients. • With severe 
vomiting or dehydration and electrolyte 
imbalance, hospitalization, fluid support, and 
specific therapy required.
Dehydration with fluid and electrolyte 
imbalance requires appropriate fluid 
replacement. Drugs that inhibit gastric 
motility (e.g., opioids) should be withdrawn.
ACTIVITY
DIET
• Dietary manipulation important in 
management of primary gastric motility 
disorders in order to speed gastric emptying. 
• Optimal diets liquid or semi-liquid 
consistency and low in fat and fiber content. 
• Small-volume meals with frequent feeding 
should be given. • Occasionally dietary 
manipulation alone is successful.
Discuss possible underlying etiologies and that 
response to therapy varies with individual cases.
• Large-breed dogs with chronic GDV 
syndrome and gastric retention should have 
surgical gastropexy. • Following gastric surgery 
generally takes several days but up to 14 days for 
return of normal motility. • Mechanical gastric 
outflow obstructions require surgical correction.
Gastric Prokinetic Agents
• Metoclopramide increases amplitude of antral 
contractions, inhibits fundic receptive relaxation, 
and coordinates duodenal and gastric motility; 
dopamine receptor antagonism in proximal GI 
tract results in increased release of acetylcholine 
from enteric neurons; at higher concentrations 
it has serotonin (5HT4) agonist effects; also has 
antiemetic effects, blocking chemoreceptor 
trigger zone in dogs, but not in cats. ◦ Oral 
dosage 0.2–0.5 mg/kg q8h given 30 min before 
meals (use lower dose in cats) or as CRI at 
1–2 mg/kg q24h. ◦ Metoclopramide generally 
considered to be weak prokinetic agent in dogs 
and recent studies suggest it has little effect at 
increasing lower esophageal sphincter pressure. 
• Cisapride works directly by cholinergic 
neurotransmission (5HT4 agonist) of GI 
smooth muscle, stimulating motility; proposed 
mechanism of action is enhancement of release of acetylcholine at myenteric plexus; increases 
lower esophageal sphincter pressure, improves 
gastric emptying, and promotes motility of 
small and large intestine. ◦ Oral dosage 
0.2–0.5 mg/kg PO q8–12h given before meals. 
◦ Cisapride currently available through 
compounding pharmacies—human product has 
been removed from market because of 
associated cardiac arrhythmias not yet noted to 
occur in dogs or cats. ◦ Mosapride (0.5–2 mg/
kg PO q12–24h) and prucalopride (0.02–
0.6 mg/kg PO q12–24h) are also 5HT4 agonist 
prokinetic agents. • Macrolide antibiotics, such 
as erythromycin, are motilin receptor agonists 
and increase GI motility; motilin is hormone 
that promotes MMC-associated motility. 
◦ Erythromycin given at low (submicrobiologic) 
doses binds motilin receptors promoting 
acetylcholine release, which speeds gastric 
emptying; dose of erythromycin for specific 
motility effects is 0.5–1 mg/kg PO q8–12h, 
given 30 min before meals. ◦ Chronic use of 
submicrobiologic doses of antibiotics not 
recommended. • H2 receptor antagonists 
ranitidine (1–2 mg/kg q8h) and nizatidine 
(2.5–5 mg/kg q24h) have reported prokinetic 
effects on gastric motility due to acetylcho -
linesterase inhibition; are considered poor 
prokinetic drugs and recent studies question 
ranitidine’s prokinetic activity in dogs; neither 
cimetidine nor famotidine affects gastric 
emptying.
Gastric prokinetic agents are contraindicated 
in patients with gastric outflow obstruction.
• Metoclopramide may cause nervousness, 
anxiety, or depression. • Cisapride may cause 
depression, vomiting, diarrhea, or abdominal 
cramping. • Erythromycin may cause vomiting.
Metoclopramide contraindicated with 
concurrent phenothiazine and narcotic 
administration or in animals with epilepsy.
• Domperidone is peripheral dopamine receptor 
antagonist that regulates motility of gastric and 
small intestinal smooth muscle similar to 
metoclopramide. • Mirtazapine is noradrenergic 
and specific serotonergic antidepressant and has 
reported gastric prokinetic effects in dogs. 
• Acotiamide is acetylcholine esterase inhibitor 
that facilitates muscarinic activity and has been 
shown to stimulate postprandial gastroduodenal 
activity in dogs at dose of 30 mg/kg, but only 
available in Asia.
  FOLLOW-UP
• Response to therapy varies with underlying 
cause. • Clinical signs are primary indicator 
of response.PREVENTION/AVOIDANCE
N/A
GDV
Length of treatment depends on ability to 
resolve underlying cause.
Gastric hypomotility may be associated with 
reflux esophagitis and reflux gastritis (see 
Bilious Vomiting Syndrome).
N/A
N/A
Avoid gastric prokinetic agents in pregnant 
animals.
SYNONYMS
• Delayed gastric emptying. • Gastric atony. 
• Gastric hypomotility.
SEE ALSO
• Bilious Vomiting Syndrome.
• Gastric Dilation and Volvulus Syndrome. 
• Gastritis, Chronic.
syndrome.
• MMC = migrating myoelectric complex.
Gaschen FP . Gastric and intestinal motility 
disorders. In: Bonagura JB, T wedt DC, eds., 
Current Veterinary Therapy XV. St. Louis, 
MO: Elsevier, 2014, pp. 513–518.
Washabau RJ. Prokinetic agents. In: 
Washabau RJ, Day MJ, eds. Canine and 
Elsevier, 2013, pp. 530–536.
Wyse CA, McLellan AM, Dickie DGM, et al. 
A review of methods for the assessment of 
the rate of gastric emptying in the dog and 
cat: 1898–2002. J Vet Intern Med 2003, 
17:609–621.
Author  Edward J. Hall
David T wedt
available online(continued)  Gastric Motility Disorders

G
550  Blackwell’s Five-Minute Veterinary Consult  
G BASICS
Inflammation of the stomach leading to 
clinical signs of >3 weeks’ duration.
• Inflammation may be secondary to drugs, 
infection, neoplasia, toxins/irritants, foreign 
material, food antigens or bacterial antigens; 
may be primary as a form of inflammatory 
bowel disease (IBD). •  Visceral receptors 
stimulated by inflammation, distension, etc. 
send signals via vagal and sympathetic nerves 
to vomiting center (medulla oblangata).
• Gastrointestinal (GI). •  Musculoskeletal—
weight loss, muscle wasting, weakness. 
• Integument—hair coat changes. •  Respiratory—
GENETICS
N/A
Common
N/A
Species
• Norwegian lundehund—chronic atrophic 
gastritis with IBD (lymphoplasmacytic); can 
progress to adenocarcinoma. •  Basenji and 
Drentse patrijshond—chronic hypertrophic 
gastritis.
Any age.
None
SIGNS
• Vomiting is most common—digested or 
undigested food, bile, frank blood, digested 
blood (“coffee grounds”); variable frequency.  
• Hyporexia to anorexia. •  Melena. •  Polydipsia. 
• Diarrhea with concurrent intestinal disease.  
• Retching. •  Burping. •  Weight loss.
• Abdominal distension ± pain. •  Ptyalism.  
• Muscle wasting, weight loss, coat changes.  
• Pallor if bleeding ulcer. •  Dehydration or 
CAUSES
• Food sensitivity. •  IBD. •  Toxins, e.g., heavy 
metals, environmental irritants (cleaners, 
herbicides). •  Metabolic/endocrine disease—
renal disease, liver disease, hypoadrenocorticism, 
pancreatitis, hyperthyroidism. •  Neoplasia—large or small cell lymphoma, adenocarcinoma, 
polyp, gastrinoma, leiomyosarcoma, plasma cell 
tumor, mast cell tumor. •  Foreign material.  
• Drugs—nonsteroidal anti-inflammatory drugs 
(NSAIDs), antibiotics, chemotherapeutics.  
• Parasitism— Toxocara  spp., Physaloptera  spp. 
(dogs and cats), Ollulanus tricuspis  (cats).  
• Helicobacter  spp. •  Pythiosis. •  Canine 
distemper virus. •  Hypergastrinemia—gas -
trinoma, achlorhydria, Basenji gastroenteropathy, 
hepatic or renal disease. •  Miscellaneous—stress, 
emphysematous gastritis (gas-forming organisms/
severe signs), benign gastric emphysema (milder 
disease/air trapping), eosinophilic sclerosing 
fibroplasia.
• Drugs (e.g., NSAIDs). •  Unsupervised/
free-roaming pets—exposure to toxin.
 DIAGNOSIS
• Any cause of GI signs. •  Esophageal 
disease—differentiate vomiting from 
regurgitation. •  Hypertrophic pyloric 
gastropathy. •  Bilious vomiting syndrome.
• Hemoconcentration if dehydrated. 
• Anemia—if blood loss (regenerative 
anemia if acute blood loss such as 
u lceration; microcytic, hypochromic with 
chronic blood loss. • Thrombocytosis with 
chronic blood loss leading to iron 
d eficiency. •  Eosinophilia with parasitism, 
neoplasia, or eosinophilic gastritis. 
• Biochemistry—prerenal or renal 
azotemia; increased blood urea nitrogen 
(BUN) : creatinine ratio with GI bleeding; 
hyperkalemia and hyponatremia with 
hypoadrenocorticism; hypochloremic 
obstruction. •  Urinalysis—unremarkable.
• Gastrin levels—elevated with gastrinoma; 
may be elevated with azotemia or use of 
antacids. •  T4. • Fecal float. •  Baseline 
cortisol ± adrenocorticotropic hormone 
(ACTH) stimulation test. •  Pythium ELISA. 
• Iron panel (iron deficiency with bleeding).
IMAGING
• Abdominal radiographs—radiopaque foreign 
material, thickened gastric wall, gastric 
distension. •  Contrast radiography—radiolu -
cent foreign material, outflow obstruction, 
delayed emptying, wall defects or thickening. 
• Ultrasonography—wall thickening, layering 
loss, ulcer, foreign object, mass.
• Upper GI endoscopy—visualize gastric 
mucosa, identify ulcer or mass, retrieve 
foreign object, biopsy (even when grossly normal), removal of small mass lesions 
(cautery), evaluate duodenum. •  Exploratory 
laparotomy—perforated ulcer, full-thickness 
biopsy, partial gastrectomy, mass removal. 
• Wireless capsule endoscopy—identify mass 
or ulcer.
• IBD—variable inflammatory infiltrate: 
lymphoplasmacytic, eosinophilic, 
n eutrophilic, granulomatous/histiocytic 
gastritis (investigate for infectious cause). 
• Helicobacter  spp. do not always convey 
pathology—significant populations deep in 
gastric glands may warrant treatment. 
• Special stains —further evaluation of 
potential neoplasia and infectious 
 TREATMENT
• Many treated as outpatients pending 
diagnostic testing or treatment trials 
(i.e., diet, drugs). •  Inpatient management 
warranted if significant dehydration or 
hypovolemia present.
• IV fluids based on patient status; caution  
for fluid overload with hypoproteinemia.  
• Enteral nutrition (nasoesophageal, 
nasogastric, or esophageal tubes) with 
persistent anorexia. •  Severe hypoalbu -
minemia—consider albumin, plasma, or 
colloids.
ACTIVITY
Restrict postoperatively if surgery performed.
DIET
• Novel protein or hydrolyzed diet when allergy 
or IBD suspected; initial response expected 
within 2 weeks; worsening warrants diet change 
or other intervention; if improvement noted, 
continue beneficial diet for several months before 
reintroducing other foods to assess tolerance.  
• Challenge with original diet can prove food 
hypersensitivity; rarely pursued. •  Low-fat diet if 
hyperacidity or gastric ulcer. •  Frequent, small 
meals (q4–6h) may provide benefit. •  Small 
late-night meal may decrease bilious vomiting.  
• Calorie requirement/diet guideline increases 
compliance. •  Unflavored or topical flea, tick, 
and heartworm preventatives. •  T reats limited to 
prescription diet. •  If commercial diet declined, 
consider home-cooked diet formulated by 
veterinary nutritionist.
• Review multiple etiologies. •  Least invasive 
testing first when patient status allows; biopsy 
for definitive diagnosis if extra-intestinal 
causes ruled out and patient fails diet and 
drug trial (i.e.. anthelminthic).Gastritis, Chronic

Canine and Feline, Seventh Edition  551
GGSURGICAL CONSIDERATIONS
• Obstructive lesion or material. •  Perforated 
ulcer. •  Removal of foreign objects if endos -
copy unsuccessful or not available. •  Full-
thickness biopsy. •  Mass resection and biopsy.
• Anthelminthic—fenbendazole (50 mg/kg PO 
q24h for 5 days), pyrantel pamoate + febantel.  
• Gastroprotectants—proton pump inhibitor 
(PPI), i.e., omeprazole (1 mg/kg PO q12h 
30–60 min before meal); also consider 
sucralfate, H2 receptor antagonist, and others 
per ACVIM consensus (see Suggested Reading). 
• Antiemetics—maropitant (1 mg/kg SC or IV 
q24h; 2 mg/kg PO q24h), ondansetron, 
metoclopramide, mirtazapine. •  Prokinetics—
metoclopramide (0.2–0.4 mg/kg PO q8h; CRI 
1–2 mg/kg/day), cisapride, ranitidine, low-dose 
erythromycin. •  IBD suspected/confirmed—
glucocorticoid (i.e., prednisone 2 mg/kg PO 
q24h or divided q12h; prednisolone for cat) 
when no clinical response to other therapeutic 
trials or in advanced disease; taper by 20–25% 
increments over time to lowest effective dose; 
discontinue when possible; total dose not 
>60 mg per day (dog); use with diet. •  If 
glucocorticoid not tolerated and/or relapse, 
consider second drug; see Alternative Drug(s).  
• Helicobacter  gastritis—several protocols have 
been described (e.g., metronidazole, amoxicillin, 
clarithromycin); see Suggested Reading.
• Do not use prokinetics if GI obstruction 
possible. •  Do not use antacids or PPIs with 
atrophic gastritis and achlorhydria.
• Immune modulation predisposes to 
secondary infections. •  Steroids can cause GI 
ulceration, diabetes mellitus. or fluid overload 
(especially cat: congestive heart failure); 
patient monitoring and client education are 
vital to success. •  Prolonged use of antacids 
or PPIs can lead to overgrowth of bacteria.
• Sucralfate will decrease absorption of other 
medications; separate by 2 hours from other 
medications. •  Omeprazole affects clearance of 
many drugs. •  Never use NSAIDs with 
glucocorticoids; high risk for GI erosion or ulcer.
• IBD—if steroid and diet alone do not 
achieve disease remission, if patient relapses, 
and/or if steroid side effects are undesirable, 
second agent may be considered; options: cyclosporine, mycophenolate, chlorambucil, 
azathioprine (never in cats); find lowest 
effective dose. •  Monitoring—exam, labwork 
(CBC, chemistry) for myelosuppression and 
other concerns (i.e., hepatic toxicity with 
cyclosporine, chlorambucil, and azathio-
prine). •  Budesonide (steroid; 1–3 mg/
patient depending on size) may have fewer 
systemic side effects; adrenal pituitary axis is 
affected.
 FOLLOW-UP
• Depends on patient severity and m  edication 
chosen; minimum—physical exam within 2 
weeks of starting treatment. •  Recheck 
abnormal labwork (i.e., e  lectrolytes, proteins) 
and monitor for medication side effects 
(i.e., hyperglycemia, anemia, myelosuppres -
sion, heptaopathy, etc. based on specific drugs 
selected). •  Recurrence warrants repeat 
diagnostics; repeat biopsy may be indicated 
(i.e., patients previously in remission of IBD 
can progress to lymphoma). •  Lack of 
response—change in medical management 
(i.e., alternative diet or drug); repeat biopsy 
(primary disease may have been missed) and 
labwork (CBC, chemistry, fecal, T4) for 
emerging comorbidity.
• Avoid drugs with high incidence of GI 
upset (i.e., doxycycline, NSAIDs). •  Avoid 
rapid diet change. •  Prevent free-roaming 
and potential for dietary indiscretion—may 
need basket muzzle in dogs.
• Gastroesophageal reflux. •  Delayed gastric 
emptying/motility disorders. •  Erosions/
ulcers. •  Aspiration pneumonia. •  Electrolyte 
or acid-base imbalances. •  Progression from 
superficial to atrophic gastritis. •  Debilitation/
death in refractory cases. •  Steroids—diabetes 
mellitus, heart failure, calcinosis cutis, muscle 
weakness, ulcers. •  Other immune-modulat -
ing drugs—bone marrow suppression, 
pancreatitis, hepatitis, GI upset.
• Varies with cause. •  Medication tapered to 
lowest effective dose ± stopped with diet.
• Foreign objects—more common in young 
animals. •  Food-responsive enteropathy—often 
younger animals. •  IBD—often middle-aged to 
older. •  Neoplasia—middle-aged to older 
animals more common.
Potential/uncommon concern secondary to 
parasites (i.e., Toxocara spp .—larval migrans).
• Prednisone—abortion, teratogenic, can 
induce parturition. •  Azathioprine—fetal 
harm; decrease sperm production.  
• Cyclosporine—fetal toxicity.
SEE ALSO
• Gastroenteritis, Eosinophilic. 
• Helicobacter  spp.
• Hypertrophic Pyloric Gastropathy, Chronic.
drug.
• https://veterinarypartner.vin.com/default.
aspx?pid=19239&id=4951472 •  https://
veterinarypartner.vin.com/default.
aspx?pid=19239&id=4951476
Leib MS. Gastric Helicobacter Species and Chronic 
Vomiting in Dogs. In: Bonagura J., T wedt D, 
eds., Kirk’s Current Veterinary Therapy XVI. St. 
Louis, MO: Elsevier, pp. 508–513.
ACVIM consensus for rational administration 
of gastrointestinal protectants to dogs and cats. 
J Vet Intern Med 2018; 32:1823–1840.
Simpson KW. Diseases of the stomach. In: 
Louis, MO: Elsevier, 2017, pp. 1495–1515.
Author  Kathryn M. McGonigle
Michelle Pressel
available online(continued)  Gastritis, Chronic

G
552  Blackwell’s Five-Minute Veterinary Consult  
G BASICS
Ulcers are defects that extend completely 
through the mucosa; erosions extend part way 
through the mucosa.
• Gastroduodenal ulceration/erosion (GUE) 
results from factors that damage or over-
whelm normal gastric mucosal defense and 
repair mechanisms. • Factors protecting the 
stomach from GUE include the mucus/
bicarbonate layer, gastric epithelial cell 
turnover, gastric mucosal blood flow, and 
local prostaglandins.
• Gastrointestinal (GI)—ulcers and erosion are 
most common in stomach, followed by proximal 
duodenum; however, neoplasia and some drugs 
(e.g., flunixin meglumine) can cause ulceration 
anywhere in GI tract. • Cardiovascular—hemor -
rhage may cause anemia, tachycardia, systolic heart 
murmur, and/or hypotension. • Peritoneal 
cavity—perforation may cause peritonitis/sepsis/
systemic inflammatory response syndrome (SIRS).
• 40–60% in racing Alaskan sled dogs. 
• Fairly common in dogs receiving nonsteroi-
dal anti-inflammatory drugs (NSAIDs) or 
dexamethasone.
Species
Dogs; rare in cats.
Chow chows, rough-coated collies, 
Staffordshire bull terriers, and Belgian 
shepherd dogs have increased incidence of 
gastric carcinoma.
Any age.
Male dogs are predisposed to gastric 
SIGNS
Severity of clinical signs is not necessarily 
proportional to size/number of GUEs.
• Some animals are asymptomatic (e.g., 
patients taking NSAIDs or dexamethasone, 
dogs working in extreme environments). 
• Hyporexia is the most common clinical 
sign. • Vomiting, hematemesis, and/or 
melena may be seen (in decreasing order of 
frequency). • Cranial abdominal pain 
(“praying position”) is rarely seen. 
• Weakness, pallor, lethargy, and/or collapse 
if severe anemia or SIRS develops.Physical Examination Findings
• Often normal. • Melena is rare. • Pale 
mucous membranes and weakness if severely 
anemic. • Tachycardia, hypotension, and 
prolonged capillary refill time if hypovolemic 
shock or perforation/SIRS.
CAUSES
Drugs
• NSAIDs—cyclooxygenase (COX)-2 selective 
NSAIDs are usually safer than nonselective 
NSAIDs; however, GUE and perforation can 
occur with all NSAIDs. Coadministration of 
glucocorticoids (either systemic or local) 
enhances ulcerogenic potential of NSAIDs. 
Some NSAIDs are renowned for being 
extremely ulcerogenic (flunixin meglumine, 
naproxen, indomethacin). • Glucocorticoids—
dexamethasone is most ulcerogenic. 
Prednisolone less likely to cause clinically 
significant GUE unless there are additional 
stress factors (e.g., hypoxemia, hypoperfusion).
GI Diseases
• GI neoplasia—carcinomas are most 
common cause of neoplastic ulceration, but 
leiomyomas/leiomyosarcomas may cause 
severe hemorrhage. • Foreign bodies can be 
associated with GUE, but not a common 
cause. Intestinal foreign bodies (especially 
linear foreign bodies) commonly cause 
intestinal ulceration/perforation. • Gastric 
Infectious Diseases
Pythiosis can cause severe GUE. It is 
regionally important and is becoming 
increasingly widespread in North America.
Metabolic Diseases
• Hepatic disease. • Hypoadrenocorticism.
Toxicity
Heavy metal poisoning (arsenic, zinc, 
thallium, iron, and lead are rare causes).
Neoplasia
• GI neoplasia (carcinoma, lymphoma, 
leiomyoma, GI stromal tumor). • Paraneoplastic 
hyperacidity (mastocytosis, gastrinoma).
Stress/Major Medical Illness
• Shock/severe hypotension (e.g., secondary 
to trauma or surgery). • SIRS (heat stroke, 
sepsis). • Burns. • Sustained strenuous 
exercise (especially in extreme environments, 
either cold or hot).
• Ulcerogenic drugs (NSAIDs, dexametha-
sone). • Hypovolemic shock/SIRS. • Extreme 
exercise.
 DIAGNOSIS
• Esophageal disease (neoplasia, esophagitis, 
foreign body)—diagnose with radiography and/or esophagoscopy. • Coagulopathies 
(thrombocytopenia, anticoagulant poisoning)—
diagnose with platelet count, coagulation 
testing. • Bronchopulmonary disease causing 
hemoptysis—diagnose with radiography and/
or bronchoscopy. • Regurgitation or vomiting 
blood (hematemesis) swallowed from 
respiratory tract or swallowed with food. 
• Pepto-Bismol and activated charcoal cause 
stool to resemble melena.
• Acute blood loss (≤3–5 days)—nonregen-
erative anemia/hypoproteinemia. • Blood loss 
>7 days—regenerative anemia/hypoproteine-
mia. • Chronic blood loss—iron deficiency 
anemia (i.e., low mean corpuscular volume 
[MCV], high red cell distribution width 
[RDW], hypochromic, variable reticulocyto-
sis) and hypoproteinemia. • Blood urea 
nitrogen (BUN) : creatinine ratio may be 
elevated with acute, severe GI hemorrhage, 
but this is hard to evaluate without recent 
pre-bleed laboratory values.
• Fecal flotation (parasitism). • Bile acids 
(hepatic insufficiency). • Resting serum cortisol 
(screen for hypoadrenocorticism). • Serum 
gastrin concentrations (gastrinoma is rare).
IMAGING
• Abdominal radiography (GI foreign body, 
abdominal mass, pneumoperitoneum, 
effusion, hepatic disease). • Barium contrast 
radiography very insensitive for GUE. 
• Ultrasonography specific but poorly 
sensitive for GI lesions (e.g., infiltrates, altered 
layering, ulcer); cannot detect erosions.
• Endoscopy most sensitive test for GUE. 
Allows biopsy of the lesion; best to biopsy 
normal-appearing tissue around GUE plus 
periphery of ulcer. Be careful biopsying center of 
ulcers as this rarely causes perforation. • Capsule 
endoscopy less expensive and does not require 
anesthesia, but not as sensitive as regular 
gastroscopy and does not allow for biopsy. 
• Fine-needle aspirates or biopsies of infiltrative 
lesions in GI tract. • Abdominocentesis may 
reveal septic peritonitis if ulcer perforates. 
• Exploratory surgery can be done to look for 
GUE, but easy to miss mucosal lesions from 
serosal surface. Can easily look into stomach 
through gastrostomy incision and miss lesions.
• GUEs are grossly visible. • Gastric body 
and antrum most common sites of GUE 
(especially from NSAIDs and steroids), but 
GUE can occur anywhere in stomach. 
• Proximal duodenal ulceration classic but 
not diagnostic for excessive gastric acid 
secretion (mast cell tumor, gastrinoma). 
• Microscopically can see inflammation, 
neoplasia, or fungal organisms.Gastroduodenal Ulceration/Erosion

Canine and Feline, Seventh Edition  553
GG TREATMENT
Very important : remove underlying cause if 
possible (e.g., drugs, toxins, poor perfusion). 
Many GUEs resolve spontaneously if cause is 
removed.
• IV fluids if needed to maintain hydration, 
gastric mucosal perfusion, and/or treat shock. 
• T ransfusions if patient is severely anemic or 
has vigorous GI hemorrhage.
ACTIVITY
Based upon patient’s condition.
DIET
• Discontinue oral intake if vomiting. • When 
feeding resumed, feed small amounts of 
low-fat/low-fiber diet.
• Dogs are especially prone to NSAID-
induced GUE because these drugs have a 
longer half-life in dogs than in humans. 
• Never administer NSAID (especially if sold 
for human use) unless specifically prescribed 
by veterinarian (e.g., low dose of aspirin 
[0.5 mg/kg q24h] is safe when used to 
prevent thromboembolic disease in dogs 
being treated with steroids). • NSAID-
associated GUE reduced by giving drug with 
food. • Proton pump inhibitors (PPIs) as 
effective as misoprostol in preventing 
NSAID-induced GUE. • No drug shown to 
be effective in preventing steroid-induced 
GUE.
• If GI blood loss potentially life threaten -
ing, perform gastroduodenoscopy to identify 
sites of hemorrhage; then either surgically 
resect lesions or cauterize sites endoscopically 
(electrically or chemically). • Surgical 
excision of ulcers indicated if medical 
treatment shows no evidence of benefit after 
5–7 days. • May need intraoperative 
endoscopy to locate lesions that cannot be 
found at surgery. • Rarely need surgeon to 
telescope intestines over tip of endoscope to 
thoroughly examine entire duodenal and 
jejunal mucosa. MEDICATIONS
• PPIs most potent inhibitors of gastric acid 
secretion. Require 3–5 days to achieve 
maximum efficacy. Used as prophylactic 
drugs and as first-line therapy for existing 
GUE; primary therapy for gastrinomas. 
Omeprazole (1–2 mg/kg PO q12h) adminis-
tered orally; pantoprazole (1 mg/kg IV q12h) 
can be administered parenterally. • Histamine 
(H2) receptor antagonists also inhibit gastric 
acid secretion. Famotidine (0.5–1 mg/kg PO/
IV q12–24h) most potent, but all of these 
drugs inferior to PPIs. • Sucralfate (0.5–1 g 
PO q6–8h) protects ulcerated tissue by 
binding to it and stimulating prostaglandin 
synthesis (use suspension instead of tablets). 
No benefit in combining with PPIs. 
• Misoprostol (2–5  μg/kg PO q12h) 
effective, but has many side effects. 
• Antiemetics if vomiting frequent or nausea 
severe. Maropitant (1 mg/kg SC q24h; 2 mg/
kg PO q24h); ondansetron (0.2–0.5 mg/kg 
PO/IV q8–12h). • Oral antacids (e.g., 
calcium carbonate) poorly effective and not 
• Sucralfate may slow absorption of other 
drugs. • Antacids may slow absorption of 
other drugs. • H2 receptor antagonists 
decrease effectiveness of PPIs. • Do not use 
misoprostol in pregnant patients.
 FOLLOW-UP
Effective medical therapy should result in 
clinical improvement within 5–7 days.
• Administer NSAIDs with food. • PPIs 
generally as effective as misoprostol at 
preventing NSAID-induced GUE. • COX-2 
selective or dual lipoxygenase (LOX)/COX 
inhibitors less likely to cause GUE than 
nonselective NSAIDs, but can still cause 
GUE and perforation/peritonitis.
Hemorrhage, perforation, septic peritonitis.EXPECTED COURSE AND PROGNOSIS
• Varies with underlying causes. • GUE not 
due to local malignancy can usually be treated 
successfully medically (especially if one can 
remove cause). However, if perforation has 
occurred, surgery is necessary.
Anemia
Neoplasia more common in older animals.
SEE ALSO
• Hematemesis.
• Melena.
• COX = cyclooxygenase.
• GUE = gastric ulceration/erosion.
• LOX = lipoxygenase.
• MCV = mean corpuscular volume. 
drug.
syndrome.
Mansfield CS, Abraham LA. Ulcer. In: 
Washabau RJ, Day MJ, eds., Canine and 
Elsevier Saunders, 2013, pp. 637–642.
Neiger R. Gastric ulceration. In: Bonagura 
JD, T wedt DC, eds., Kirk’s Current 
Elsevier Saunders, 2009, pp. 497–501.
Ettinger SJ, Feldman EC, Cote E, eds., Textbook 
of Veterinary Internal Medicine, 8th ed. St. 
Louis, MO: Elsevier, 2017, pp. 1495–1516.
Author  Michael D. Willard
available online(continued)  Gastroduodenal Ulceration/Erosion

G554  Blackwell’s Five-Minute Veterinary Consult  
GGastroenteritis, Acute Hemorrhagic Diarrhea Syndrome
  BASICS
A peracute hemorrhagic enteritis of dogs 
characterized by a sudden onset of severe 
bloody diarrhea that is often explosive, with 
vomiting (typically the first clinical sign 
observed by the owner), hypovolemia, and 
usually marked hemoconcentration due to a 
dramatic loss of fluid into the intestinal lumen.
• Many conditions result in hemorrhagic 
diarrhea, but the acute hemorrhagic diarrhea 
syndrome (AHDS) of dogs appears to have 
unique clinical features that distinguish it from 
other conditions. • AHDS results in a peracute 
loss of intestinal mucosal integrity with the 
rapid movement of fluid and electrolytes into 
the gut lumen. Dehydration and hypovolemic 
shock occur quickly. In proportion to fluid 
loss, blood loss is usually minor. This has to be 
differentiated from true gastrointestinal (GI) 
bleeding, in which anemia is usually observed. 
Protein loss can be substantial in some cases, 
resulting in severe hypoalbuminemia. 
T ranslocation of bacteria or toxins through the 
damaged intestinal mucosa can usually be 
compensated. In a few cases the immune 
defense mechanisms can be overwhelmed, 
resulting in septicemia/septic shock.
• GI. • Cardiovascular.
GENETICS
Unknown; small or toy breeds appear to be 
Unknown; appears to be common.
N/A
Species
Dog
• Any breed can be affected; incidence is 
greater in small and toy breeds. • Breeds most 
represented include Yorkshire terrier, 
miniature pinscher, miniature schnauzer, 
miniature poodle, and Maltese.
Usually in adult dogs with a mean age of 5 
years.
N/A
SIGNS
• Mucosal lesions are restricted to the 
intestines and cannot be detected in the 
stomach histologically; therefore, it is suggested 
to replace the term hemorrhagic gastroenteritis 
(HGE), implicating gastric inflammation, with AHDS. • Most animals affected are previously 
healthy with no historical environmental 
changes; some dogs have a history of chronic 
intermittent GI disease. • Clinical findings are 
variable in both the course and severity of the 
disease; the disease is usually acute to peracute; 
with adequate fluid and symptomatic 
treatment, rapid clinical improvement is 
typically observed in the first 48 hours.
• Acute vomiting, anorexia, and lethargy, 
followed by watery diarrhea quickly changing 
to bloody diarrhea. • Signs progress rapidly 
and become severe within a period of <12 
hours as a result of hypovolemic shock and 
hemoconcentration.
• Evidence of hypovolemia; lethargy, weakness, 
tachycardia, prolonged capillary refill time, and 
weak pulse pressure. • Skin turgor as a 
reflection of dehydration may appear normal 
owing to the peracute nature of the disease and 
the lag time in compartmental fluid shifts. 
• Abdominal pain and fluid-filled bowel can be 
detected. • Rectal examination identifies 
bloody diarrhea, and later in the course of 
disease a “raspberry jam” characteristic stool 
develops. • Often normo- or hypothermia; 
fever is unusual and represents an important 
feature differentiating uncomplicated AHDS 
cases from dogs with infection and systemic 
reaction to an enteropathogen or septicemia 
following bacterial translocation.
CAUSES
• There is increasing evidence to suggest that 
Clostridium perfringens  type A is involved, as 
these bacteria have been identified on necrotic 
mucosal surfaces closely associated with 
epithelial lesions. • A novel pore-forming toxin 
designated NetF was detected in C. perfringens  
type A strains, which were involved in AHDS; 
compared to healthy control dogs (prevalence: 
0–10%), the prevalence of C. perfringens  
encoding the netF gene is significantly higher 
in dogs with AHDS (50–55%). • Other 
undetected clostridial toxins might be involved 
in the disease process; it is also possible that 
different etiologies are responsible for this 
syndrome in different patients.
• Unknown. • Some dogs have a history of 
chronic intermittent diarrhea.
  DIAGNOSIS
• Drugs/toxins causing mucosal irritation 
(e.g., nonsteroidal anti-inflammatory drugs, 
high-dose corticosteroids, doxycycline). 
• Parvovirus. • Circovirus. • Acute GI 
ulceration. • Bacterial enteritis such as 
salmonellosis or campylobacteriosis. 
• Conditions resulting in endotoxic or hypovolemic shock. • Intestinal obstruction 
or intussusception. • Hypoadrenocorticism. 
• Heat stroke. • Pancreatitis. • Coagulopathy.
• Marked hemoconcentration with packed 
cell volume (PCV) usually >60%, with 
discordant plasma proteins that are normal to 
decreased due to protein loss into the GI tract; 
some dogs show significant hypoalbuminemia 
after rehydration; usually a stress leukogram. 
• Biochemistry profile may reveal secondary 
hepatic enzyme elevations and high blood urea 
nitrogen (BUN) due to prerenal causes.
Fecal Tests
• Stool is negative for parasites. • ELISA and 
PCR for parvovirus are negative. • Fecal 
cytology shows many red blood cells (RBCs) 
and occasional white blood cells (WBCs). 
• Clostridium  spp. may be cultured from 
healthy dogs and should not be used as a 
diagnostic test for AHDS. Fecal ELISA test for 
detection of C. perfringens  enterotoxin is often 
positive. A culture for other enteric pathogens 
is not diagnostic, since many enteropathogens 
can be found in feces of healthy dogs. Fecal 
PCR for detection of C. perfringens  alpha toxin 
gene alone is not sufficient to diagnose this 
disorder. A positive PCR for netF encoding 
C. perfringens  strains is suggestive for AHDS.
Coagulogram
Usually normal, but rarely secondary 
is a complication.
IMAGING
Abdominal radiographs or ultrasound show 
fluid- and gas-filled small and large intestine. 
Ultrasonography often reveals fluid-filled 
intestinal loops without peristaltic movements 
due to the presence of a paralytic ileus.
Endoscopy
• Rarely indicated. • Stomach may appear 
normal, but small and large intestine will show 
diffuse mucosal hemorrhage, and hyperemia.
• Gross findings include intestinal 
congestion. • Histological examination of the 
intestinal tract shows superficial mucosal 
hemorrhagic necrosis without significant 
inflammation. • Frequently, layers of 
rod-shaped bacteria (e.g., C. perfringens ) can 
be detected on the surface of the intestinal 
mucosa. • Gastric mucosa is spared.
  TREATMENT
Patients suspected of having AHDS should 
be hospitalized and treated aggressively, 
because clinical deterioration is often rapid 
and can be fatal.

Canine and Feline, Seventh Edition  555
GGNURSING CARE
• Rapid volume replacement through a large-  
bore IV catheter is required in all cases. 
• Balanced electrolyte solutions are given up to 
the rate of 40–60 mL/kg/hour IV until PCV 
<50%. • Shock fluids can also be given as fast as 
30 mL/kg in 10 min; this bolus can be repeated 
up to three times if needed. • A moderate rate 
of maintenance fluids is given to maintain 
circulatory function and correct any potassium 
or other electrolyte deficits during the recovery 
period. • Continued GI fluid losses should be 
estimated and that volume added to the fluid 
requirements. • Hypoproteinemic animals may 
require colloids, plasma, or albumin solutions 
(canine preferred over human, if available).
ACTIVITY
DIET
• NPO during acute phase as long as dogs are 
vomiting. • T rickle feeding with oral glutamine 
solution or low-fat (liquid) diet as long as the 
dog is not eating. • During recovery period a 
bland, low-fat, low-fiber GI diet should be fed 
for several days before returning to normal 
diet. • Consider increased dietary fiber to alter 
the intestinal microbiota to reduce the 
likelihood of recurrence of C. perfringens –
• Discuss the need for immediate and 
aggressive medical management; with 
appropriate therapy, mortality is usually low. 
• Recurrence is reported in about 10% of cases.
N/A
• Antibiotics should be restricted to dogs with 
signs of systemic infection, immunosuppression, 
and reduced liver function, as well as to dogs 
inadequately responding to symptomatic 
therapy; amoxicillin/sulbactam (50 mg/kg q8h 
IV) is suggested prophylactically in dogs that 
cannot be monitored closely. • An antiemetic 
such as maropitant (1 mg/kg q24h IV) is 
suggested to control nausea and vomiting. 
• Analgesics (e.g., buprenorphine 0.01 mg/kg 
q6–8h IV) should be administered at the 
clinician’s discretion. • Excessive blood loss may 
require blood transfusion (very rare).
N/A
Septic and or hypovolemic shock can occur 
quickly and consequently the animal should 
be monitored closely.
N/AALTERNATIVE DRUG(S)
• Oral antibiotics and intestinal protectants are 
of little benefit and generally not administered. 
• Administration of mucosal protectants such as 
sucralfate is of questionable value. 
• Antidiarrheal drugs are contraindicated. 
• High-dose, multistrain probiotic therapy 
might help to displace C. perfringens  strains 
from the GI tract, though clinical efficacy has 
not been evaluated. • Long-term administration 
of probiotics could theoretically alter the 
intestinal microbiota to reduce the likelihood of 
recurrence of C. perfringens –associated diarrhea, 
though clinical efficacy has not been evaluated.
  FOLLOW-UP
• Check response to fluid therapy by assessing 
heart rate, capillary refill time, pulse pressure, 
as well as mental status and urine production 
every hour until considering the dog stable. 
• Monitor PCV and total solids frequently (at 
least every 4–6 hours). • Modify fluid 
replacement based on patient status. • If there 
is failure of clinical improvement in 24–48 
hours, reevaluate the patient, as other causes 
of hemorrhagic diarrhea are probable.
N/A
• Occasionally DIC may develop. • Neurologic 
signs or seizures secondary to hemoconcentration 
may occur. • Cardiac arrhythmias occur from 
suspected myocardial reperfusion injury.
• Most dogs recover; mortality rate can be 
high in untreated dogs; fewer than 10% of 
treated dogs die, and 10–15% have repeated 
occurrences. • The course of the disease is 
generally short, lasting from 24 to 72 hours. 
• About 50% of dogs still have soft feces on 
day 5. • Time to complete normalization of 
stool consistency can be up to 7–10 days.
N/A
N/A
Unknown
N/A
SYNONYMS
(Acute) HGE.
SEE ALSO
• Acute Diarrhea. • Acute Vomiting.ABBREVIATIONS
syndrome. • BUN = blood urea nitrogen. 
coagulation. • GI = gastrointestinal. • HGE 
= hemorrhagic gastroenteritis. • PCV = 
packed cell volume. • RBC = red blood cell. 
Busch K, Suchodolski JS, Kuhner KA, et al. 
Clostridium difficile toxin A/B do not play 
a role in acute haemorrhagic diarrhoea 
syndrome in dogs. Vet Rec 2015, 176:253.
Hall JH. Small intestine. In: Washabau RJ, 
2013, pp. 651–728.
Mehdizadeh Gohari I, Parreira VR, Nowell 
VJ, et al. A novel pore-forming toxin in 
type A Clostridium perfringens is associated 
with both fatal canine hemorrhagic 
gastroenteritis and fatal foal necrotizing 
enterocolitis. PLoS One 2015, 
10:e0122684.
Mortier F , Strohmeyer K, Hartmann K, et al. 
Acute haemorrhagic diarrhoea syndrome in 
dogs: 108 cases. Vet Rec 2015, 176:627.
Sasaki J, Goryo M, Asahina M, et al. 
Hemorrhagic enteritis associated with 
Clostridium perfringens  type A in a dog. 
J Vet Med Sci 1999, 61:175–177.
Spielman BL, Garvey MS. Hemorrhagic 
gastroenteritis in dogs. J Am Anim Hosp 
Assoc 1993, 29:341–344.
Unterer S, Lechner E, Mueller RS, et al. 
Prospective study of bacteraemia in acute 
haemorrhagic diarrhoea syndrome in dogs. 
Vet Rec 2015, 176:309.
Unterer S, Strohmeyer K, Kruse BD, et al. 
T reatment of aseptic dogs with hemorrhagic 
gastroenteritis with amoxicillin/clavulanic 
acid: a prospective blinded study. J Vet 
Intern Med 2011, 25:973–979.
Author  Stefan Unterer
David C. T wedt.
available online(continued)  Gastroenteritis, Acute Hemorrhagic Diarrhea Syndrome

G
556  Blackwell’s Five-Minute Veterinary Consult  
GGastroenteritis, Eosinophilic
  BASICS
• Disease of gastrointestinal (GI) tract caused 
by primary infiltrate of eosinophils. • When 
other causes of eosinophilic infiltrates are 
ruled out, this is considered a form of 
inflammatory bowel disease (IBD).
• Eosinophils involved in innate, acquired, 
and adaptive immunity; antigenic stimulation 
causes eosinophilic recruitment to GI tract. 
• Stimulation from food hypersensitivity, 
parasitic infection, neoplasia (i.e., mast cell, 
lymphoma), fungi, viruses, bacteria, disease 
affecting mast cells, or idiopathic. • Small and 
large eosinophil granules release substances 
cytoxic to microorganisms and recruit other 
immune defenses; also damaging to self 
tissues. • Eosinophils activate mast cells 
directly causing continued tissue destruction.
• GI—primarily stomach and small intestine; 
large intestine less commonly affected; esophagus 
rarely affected. • Hemic/lymphatic/immune—
hypereosinophilic syndrome (HES) and certain 
neoplasms affect spleen and lymph nodes. 
• Hepatobiliary—HES may affect liver. 
• Respiratory—aspiration pneumonia secondary 
to vomiting. • Musculoskeletal—weight loss, 
muscle wasting, weakness. • Integument—hair 
coat changes with nutritional deficiencies.
GENETICS
Unknown
• Unknown. • Second most common form 
of IBD.
N/A
Species
German shepherd, boxer, Rottweiler, 
Doberman pinscher, and shar-pei.
• Any age. • Dogs—commonly young (<5 
years). • Cats—commonly middle-aged.
None
SIGNS
Signs vary with severity of illness and sites 
affected.
• Vomiting, small bowel diarrhea > large 
bowel diarrhea. • Abdominal pain. 
• Anorexia/hyporexia. • Weight loss. 
• Occasional melena.Physical Examination Findings
• Cats > dogs—thickened bowel loops on 
abdominal palpation. • HES—skin lesions, 
enlarged peripheral lymph nodes, hepato -
splenomegaly. • Abdominal pain. • Muscle 
wasting, weight loss, ± coat changes. • Pale 
mucous membranes with bleeding ulcer. 
• Dehydration, hypovolemia. • Palpable 
abdominal mass lesion.
CAUSES
• IBD. • Parasites—e.g., Physaloptera  spp., 
Ollulanus tricuspis , Spirocerca  spp. • Fungal, viral, 
bacterial infection. • Loss of tolerance to normal 
intestinal flora. • Systemic mastocytosis. • HES. 
• Neoplasia—mast cell tumor, lymphoma.
N/A
  DIAGNOSIS
• Any cause of GI signs. • Feline GI 
eosinophilic sclerosing fibroplasia (ulcerated 
intramural mass at pyloric sphincter or 
ileocecocolic junction most common).
• Hemogram—unremarkable, mild to marked 
peripheral eosinophilia (cats > dogs). 
• Biochemistry—blood urea nitrogen (BUN) 
elevation alone or disproportionally higher than 
creatinine suggests GI bleeding; hypoproteinemia 
and hypocholesterolemia common with 
significant disease; increased liver enzyme 
activity and/or azotemia may be seen with 
HES; prerenal azotemia with dehydration. 
• Urinalysis—usually unremarkable.
• Buffy-coat smear—evaluate for systemic 
mastocytosis. • Serum cobalamin and 
folate—screen for evidence of intestinal 
malabsorption. • Fecal float, multiple. 
• Baseline cortisol ± adrenocorticotropic 
hormone (ACTH) stimulation test. • Based 
on location or travel history, testing for fungal 
organisms (i.e., histoplasmosis). • Expanded 
infectious disease testing depending on 
patient risk and exposure.
IMAGING
• Abdominal radiography—rules out other 
disease causing clinical signs; does not diagnose 
this condition; hepatosplenomegaly may be seen 
with HES. • Barium contrast radiography may 
demonstrate thick intestinal walls and mucosal 
irregularities, but does not provide etiology. 
• Ultrasonography—assess stomach and 
intestinal wall thickness; assess for mass lesions, 
ulcer, and obstruction; rule out other diseases; 
examine liver, spleen, and mesenteric lymph 
nodes with suspected HES or metastatic disease.
• Upper and lower GI endoscopy—visualize 
mucosa; identify ulcer or mass; biopsy (even 
when grossly normal); thickened rugal folds, increased mucosal friability, villous blunting, 
edema, and erythema are commonly 
visualized; intestinal parasites may be seen. 
• Fine-needle aspirate and cytology of 
enlarged liver, spleen, and/or lymph nodes. 
• Bone marrow aspirate cytology—when 
systemic mastocytosis or severe peripheral 
eosinophilia is present. • Exploratory 
laparotomy—perforated ulcer; full-thickness 
biopsy; removal of obstructive lesion and/or 
biopsy of other affected organs (lymph node, 
spleen, liver).
• Eosinophilic infiltrates can be patchy in 
intestine; multiple biopsies always 
recommended. • Histopathology reveals 
diffuse mucosal infiltrate of eosinophils; 
submucosa and muscularis are less commonly 
involved in the dog (more common in the 
cat); infiltrate of muscularis layer associated 
with obstructive eosinophilic lesions; 
eosinophilic inflammation within fibroplasia 
seen in feline GI eosinophilic sclerosing 
fibroplasia; WSAVA guidelines from 
international GI Standardization Group 
should be followed for interpretation of 
normal vs. pathologic numbers of eosinophils.
  TREATMENT
• Many treated as outpatients (minimal 
dehydration) after obstruction excluded, 
pending diagnostic testing or treatment trials 
(i.e., diet trial, drugs). • Inpatient medical 
management if significant dehydration or 
intractable vomiting.
• IV fluids to restore volume and correct 
dehydration when indicated; caution  for fluid 
overload with hypoproteinemia. • Enteral 
nutrition (nasoesophageal, nasogastric, or 
esophageal tubes) with persistent anorexia. 
• Severe hypoalbuminemia—consider 
albumin, plasma, or colloids.
ACTIVITY
DIET
• Novel protein or hydrolyzed diet when 
allergy or IBD suspected; initial response 
expected within 2 weeks; worsening warrants 
diet change or other intervention; if 
improvement noted, continue diet for several 
months before reintroducing other foods to 
assess tolerance. • Challenge with original 
diet can prove food hypersensitivity; rarely 
pursued. • Calorie requirement/diet guideline 
increases compliance. • Unflavored or topical 
flea, tick, and heartworm preventatives. 
• T reats limited to prescription diet. • If 
commercial diet declined, consider home-
cooked diet formulated by veterinary 
nutritionist.

Canine and Feline, Seventh Edition  557
GGCLIENT EDUCATION
• Review multiple etiologies. • Least invasive 
for definitive diagnosis if extra-intestinal causes 
ruled out and patient fails diet and drug trial 
(i.e., anthelminthic, antimicrobial). • Potential 
for waxing and waning nature; necessity for 
lifelong vigilance regarding inciting factors; 
potential for long-term therapy.
• Obstructive lesion. • Perforated ulcer. 
• Full-thickness biopsy.
• Gastroprotectants and antiemetics often 
needed to control clinical symptoms initially. 
(PPI), i.e., omeprazole 1 mg/kg PO q12h 
30–60 min before meal; also consider 
per ACVIM consensus (see Suggested 
Reading). • Antiemetics—maropitant (1 mg/
kg SC/IV q24h; 2 mg/kg PO q24h); 
ondansetron, metoclopramide, mirtazapine. 
• Prokinetics—metoclopramide (0.2–0.4 mg/
kg PO q8h; CRI 1–2 mg/kg/day), cisapride, 
ranitidine, low-dose erythromycin. 
•Anthelminthic—fenbendazole (50 mg/kg 
PO q24h for 5 days), pyrantel pamoate + 
febantel. • Antimicrobial—metronidazole 
(10 mg/kg PO q12h for 2–4 weeks), tylosin 
(11–20 mg/kg PO q12h for 2–4 weeks). 
• IBD suspected/confirmed—glucocorticoid 
(i.e., prednisone 2 mg/kg PO q24h or divided 
q12h; prednisolone for cat) when no clinical 
response to other therapeutic trials or in 
advanced disease; taper by 20–25% 
>60 mg per day (dog); use with diet. • If 
consider second drug; see Alternative Drug(s).
Do not use prokinetics if GI obstruction 
possible.
secondary infections. • Steroids can cause GI 
ulceration, diabetes mellitus, or fluid overload 
vital to success. • Prolonged use of antacids 
medications. • Omeprazole affects clearance 
of many drugs. • Never use nonsteroidal 
anti-inflammatory drugs (NSAIDs) with 
glucocorticoid; high risk of GI erosion/ulcer.ALTERNATIVE DRUG(S)
and/or if steroid side effects undesirable, 
second agent may be considered; options: 
cyclosporine, mycophenolate, chlorambucil, 
and azathioprine (never in cats); find lowest 
effective dose. • Monitoring—exam, labwork 
cyclosporine, chlorambucil, and azathioprine). 
• Leukotriene receptor blockers (i.e., 
montelukast) have been successful in humans. 
• Budesonide (steroid; 1–3 mg/patient 
depending on size) may have fewer systemic 
side effects; adrenal pituitary axis affected.
  FOLLOW-UP
• Depends on patient severity and 
medication chosen; minimum: physical exam 
within 2 weeks of starting treatment. 
• Monitoring peripheral eosinophil count if 
initially elevated. • Recheck abnormal 
labwork (i.e., electrolytes, proteins) and 
monitor for medication side effects (i.e., 
hyperglycemia, anemia, myelosuppression, 
heptaopathy, etc. based on specific drugs 
selected). • Recurrence warrants repeat 
can progress to lymphoma). • Lack of 
• Avoid rapid diet change. • Prevent free-
roaming and potential for dietary indiscretion—  
may need basket muzzle in dogs.
• Gastroesophageal reflux disease (GERD). 
• Delayed gastric emptying/motility disorders. 
• Erosions/ulcers. • Aspiration pneumonia. 
• Electrolyte, acid-base imbalances. 
• Debilitation/death in refractory cases. 
• Steroid—diabetes mellitus, heart failure, 
calcinosis cutis, muscle weakness, ulcers. • Other 
immune-modulating drugs—bone marrow 
suppression, pancreatitis, hepatitis, GI upset.
• Vary with cause. • Medication tapered to 
• Food-responsive enteropathy—often 
younger. • IBD—often middle-aged to older. 
• Neoplasia—middle-aged to older animals 
parasites (i.e., Toxocara  spp.—larval migrans).
induce parturition. • Azathioprine—fetal 
harm; decreases sperm production. 
SEE ALSO
• Gastroduodenal Ulceration/Erosion. 
• BUN = blood urea nitrogen. • GERD = 
gastroesophageal reflux disease. • GI = 
gastrointestinal. • HES = hypereosinophilic 
syndrome. • IBD = inflammatory bowel disease. 
drug. • PPI = proton pump inhibitor.
aspx?pid=19239&id=7393377 • https://
Hall EJ, Day MK. Diseases of the small 
intestine. In: Ettinger SJ, Feldman EC, eds., 
1516–1564.
Linton M, Nimmo JS, Norris JM, et al. 
Feline gastrointestinal eosinophilic 
sclerosing fibroplasia: 13 cases and review of 
an emerging clinical entity. J Feline Med 
Surg 2015, 17:392–404.
Sattasathuchana O, Steiner JM. Canine 
eosinophilic gastrointestinal disorders. 
Anim Health Res Rev 2014, 15(1):76–86.
available online(continued)  Gastroenteritis, Eosinophilic

558  Blackwell’s Five-Minute Veterinary Consult  
GGastroesophageal Reflux
  BASICS
OVERVIEW
• Reflux of gastric or intestinal fluid into the 
esophageal lumen.
• Incidence unknown; probably more 
common than clinically recognized.
• T ransient relaxation of the lower esophageal 
sphincter (LES) or chronic vomiting may 
permit reflux of gastrointestinal juices into 
the esophageal lumen. Reflux is common in 
dogs with sliding hiatal hernias. A small 
amount of gastroesophageal reflux (GER) is a 
normal phenomenon in dogs and cats.
• Gastric acid, pepsin, trypsin, bicarbonate, 
and bile salts are all injurious to the 
esophageal mucosa with prolonged or 
repetitive contact.
• Sequelae of GER may vary from mild 
inflammation of the superficial mucosa to 
severe ulceration involving the submucosa 
and muscularis.
• Systems affected include gastrointestinal 
(regurgitation) and respiratory (aspiration 
pneumonia).
• Dog and cats; male or female.
• No breed predilections reported.
• May be associated with congenital hiatal 
hernia seen in Chinese Shar-Pei dogs and 
• Occurs at any age; younger animals may be 
at increased risk because of developmental 
immaturity of the gastroesophageal sphincter.
SIGNS
• Painful swallowing (odynophagia).
• Retained gastric contents.
• Acquired or congenital hiatal hernia.
• Chronic vomiting with secondary 
• Brachycephalic airway syndrome.
  DIAGNOSIS
• Oral or pharyngeal disease.
• Ingestion of caustic agent.
• Esophageal tumor.
N/A
IMAGING
• Survey thoracic radiography—usually 
unremarkable; may be air or fluid in the distal 
esophagus (nonspecific finding).
• Barium contrast radiography—reveals GER 
in some, but not all, animals; videofluoroscopy 
is superior to esophagram; aspiration 
pneumonia may be evident in the dependent 
portions of the lung.
Esophagoscopy—the best means of 
confirming esophagitis: irregular mucosal 
surface with hyperemia or active bleeding 
often present in the distal esophagus. 
Refluxed gastroduodenal secretions may be 
seen pooling in the distal esophagus near the 
LES, which may or may not be open.
  TREATMENT
• Generally managed as outpatient.
• Not necessary to restrict activity.
• Moderate to severe cases—may withhold 
food for 24 hours to promote esophageal rest 
and to minimize further GER; thereafter, feed 
low-fat, low-protein meals in small, frequent 
feedings; dietary fat decreases gastroesophageal 
sphincter pressure and delays gastric 
emptying; protein stimulates gastric acid 
secretion and may precipitate GER.
• Drug therapy is recommended if significant 
mucosal injury is present.
• Oral sucralfate slurry (0.5–1 g PO q8h).
• Proton pump inhibitors (omeprazole: 
0.7–1.5 mg/kg PO q12h or pantoprazole: 
1 mg/kg IV q12–24h) for robust suppression 
of gastric acid production.
• Prokinetic agents—cisapride (0.5 mg/kg 
PO q8–12h) or metoclopramide (0.5 mg/kg 
PO q6–8h or 1–2 mg/kg q24h as CRI).
nutrition in animals with severe mucosal 
trauma.
Sucralfate may interfere with the absorption 
of other drugs.  FOLLOW-UP
• It is appropriate in most patients to 
monitor clinical signs.
• Consider endoscopy for patients that do 
not respond to empirical medical therapies. 
Severe mucosal damage (esophagitis) may 
progress to stricture.
Clients should avoid feeding high-fat foods; 
they promote gastric retention and might 
exacerbate GER.
Esophagitis and stricture formation.
Most animals respond well to medical 
management and have a good prognosis.
Hiatal hernia.
May be worse in younger animals because of 
developmental immaturity of the gastro -
esophageal sphincter mechanism.
N/A
N/A
SEE ALSO
Kook PH, Kempf J, Ruetten M, Reusch CE. 
Wireless ambulatory esophageal pH 
monitoring in dogs with clinical signs 
interpreted as gastroesophageal reflux. J Vet 
Intern Med 2014, 28(6):1716–1723.
Zacuto AC, Marks SL, Osborn J, et al. The 
influence of esomeprazole and cisapride on 
gastroesophageal reflux during anesthesia in 
dogs. J Vet Intern Med 2012, 
26(3):518–525.

Canine and Feline, Seventh Edition  559
GGastrointestinal Obstruction
  BASICS
The partial or complete physical impedance 
to the flow of ingesta and/or secretions 
aborally through the pylorus into the 
duodenum (gastric outflow tract obstruction 
[GOTO]) or through the small intestine. 
Obstructions in the pharynx, esophagus, large 
intestine, and rectum, and motility disorders, 
are addressed in separate chapters.
• Mechanical obstruction commonly results 
from indiscriminate ingestion of foreign 
material, the presence of a gastrointestinal 
(GI) mass, or intussusception. • The 
accumulation of ingesta and GI secretions 
orad to the obstruction causes local vascular 
compromise, resulting in intestinal wall 
edema, necrosis, and possible sepsis. 
• Decreased oral intake, vomiting, and 
sequestration of GI secretions result in 
acid-base and electrolyte imbalances.
• Cardiovascular—hypovolemic or septic 
shock can result from fluid loss or GI 
translocation of bacteria. • GI—GI 
obstructions cause pathology by distension 
and compression of the GI tract orad to the 
obstruction; this results in decreased blood 
flow to the area with subsequent edema, 
ulceration, and necrosis of the mucosa; direct 
physical damage to the GI mucosa by foreign 
bodies (especially linear foreign bodies) can 
result in ulceration and possible perforation 
of the intestinal wall. • Hemic/lymphatic/
immune—sepsis secondary to necrosis and/or 
bacterial translocation.
GENETICS
Unknown
Common
Species
Gastric dilation and volvulus (GDV) is 
common in large- and giant-breed dogs 
(Great Dane, German shepherd).
• Foreign bodies—more common in young 
animals, but can occur at any age. • Pyloric 
stenosis—occurs most often in young 
animals. • Chronic hypertrophic gastropathy 
(CHG)—more common in middle-aged and 
older animals. • Intussusceptions—most 
common in young animals.
NoneSIGNS
• Severity of clinical signs is influenced by 
location and completeness of obstruction. 
• Patients with GOTO tend to have acute 
onset of severe vomiting; some patients can 
present as acute abdomen (acute and severe 
abdominal pain, vomiting); partial 
obstructions can have more chronic and 
intermittent clinical signs. • Duration of 
clinical signs varies, but usually 2–3 days. 
• Patients may have vomiting, anorexia, and/
or lethargy.
• Moderate to severe dehydration is common. 
• Careful oral examination is recommended 
as linear foreign bodies can often be lodged at 
the base of the tongue. • Abdominal 
palpation will often elicit a painful response; 
sometimes patients will vomit in response to 
palpation. • Abdominal mass may be 
palpated. • Cranial abdominal distension and 
tympany often seen with GDV.
CAUSES
• Benign pyloric outflow tract obstruction. 
• Foreign body. • Gastroenteritis (infectious, 
granulomatous). • GDV. • GI neoplasia. 
• Intussusception. • Mesenteric torsion/
volvulus. • Pyloric stenosis. • Stricture.
• Foreign bodies more commonly found in 
young dogs and cats (mean age 2–4 years) 
due to indiscriminate eating behavior. 
• Linear foreign bodies found more 
commonly in cats. • GI tumors more 
common in older cats and dogs.
  DIAGNOSIS
• Metabolic disease (e.g., renal failure, hepatic 
disease, diabetic ketoacidosis, 
hypoadrenocorticism). • Infectious 
gastroenteritis (e.g., viral, bacterial, parasitic). 
• Nonspecific gastroenteritis. • Pancreatitis. 
• Peritonitis. • Gastroduodenal ulcer and 
erosion. • CNS disease.
• CBC—will often reflect systemic 
consequences of obstruction; variable degrees 
of neutrophilia with left shift and possible 
toxic changes seen with cases of sepsis. 
• Biochemistry—often reveals changes 
secondary to dehydration (increased blood 
urea nitrogen [BUN] and creatinine) as well as 
electrolyte and acid-base disturbances; animals 
with GOTO classically have hypokalemic 
and hypochloremic metabolic alkalosis. 
• Urinalysis—urine specific gravity may be 
increased secondary to dehydration.OTHER LABORATORY TESTS
Lactate—hypoperfusion results in 
hyperlactatemia (>2.5 mmol/L).
IMAGING
• Survey abdominal radiographs—radiopaque 
foreign material may be seen in GI lumen; 
presence of soft tissue opacity in the stomach 
in a patient with recent history of vomiting 
and anorexia is highly suspicious for GOTO; 
indirect signs of GI obstruction can include 
gastric or intestinal distension with fluid or 
gas; linear foreign bodies characteristically 
cause grouping of intestinal loops on right of 
midline with small luminal gas bubbles 
(apostrophe shaped); presence of free gas in 
abdomen is consistent with GI perforation 
and septic peritonitis. • Contrast abdominal 
radiographs—positive contrast agents (liquid 
barium) can be used to identify radiolucent 
material in GI lumen; retained contrast 
material in stomach 4–6 hours after 
administration is consistent with GOTO; 
use of barium contrast agents contraindicated 
if GI perforation is suspected; in these 
instances, use of iodinated contrast agents is 
recommended. • Abdominal ultrasound—
ultrasound can be very effective at identifying 
GI foreign bodies and intraluminal masses as 
well as assessing for integrity of GI tract and 
presence of abdominal fluid/air; luminal 
foreign bodies will cause distal acoustic 
shadowing, while linear foreign bodies often 
appear as hyperechoic linear objects within 
intestinal lumen.
• In cases where intestinal neoplasia is 
suspected, advanced imaging techniques such 
as CT may provide additional information 
such as the nature of the mass and its degree 
of invasion. • GI endoscopy may be used for 
removal of gastric foreign bodies causing 
GOTO.
Histopathology of GI masses causing 
obstruction can reveal granulomatous 
inflammation, fungal infection (e.g., 
pythiosis), and neoplasia.
  TREATMENT
• Emergency intervention is required to relieve 
the obstruction .
• Prior to definitive treatment of the 
obstruction, stabilization of the patient and 
correction of dehydration as well as electrolyte 
and acid-base abnormalities are imperative. 
• Dogs with GDV should have gastric 
decompression first using orogastric 
intubation or percutaneous gastrocentesis in 
order to relieve gastric pressure.

560  Blackwell’s Five-Minute Veterinary Consult  
GNURSING CARE
• Aggressive IV administration of isotonic 
crystalloids is recommended to correct 
dehydration and hypovolemia, if present; 
recommendation is to administer ¼ shock bolus 
of 20 mL/kg (dog) or 10 mL/kg (cat) over 15 
min and reevaluate patient’s status (heart rate, 
blood pressure, blood lactate); repeat 1–2 times 
if vital parameters fail to normalize; if crystalloid 
therapy not successful in stabilizing patient, 
colloid solutions such as hetastarch can be 
administered at 5 mL/kg (dog) and 2.5 mL/kg 
(cat), to max 20 mL/kg (dog) and 10 mL/kg 
(cat). • Colloids should be used with caution, 
especially in cases where sepsis is suspected, due 
to their association with acute kidney injury.
ACTIVITY
Restricted for first 10–14 days post surgery.
DIET
• Nothing by mouth until relief of 
obstruction and resolution of vomiting; then 
feed bland fat-restricted diet for 1–2 days, 
with gradual return to normal diet. • Enteral 
tube feeding or parenteral feeding may be 
required postoperatively.
Animals with a history of GI foreign bodies 
have a tendency to repeat this behavior; 
owners should be counseled on ways to 
minimize ingestion of these objects.
• Surgical exploration of the abdomen allows 
for removal of the foreign body as well as 
resection of any nonviable tissue; if the 
obstruction is neoplastic, infectious, or 
inflammatory in nature, surgical intervention 
can be therapeutic as well as diagnostic as 
long as excised tissue is submitted for 
histopathology and culture. • When GI 
obstruction is caused by a gastric foreign 
body, endoscopic removal can be attempted; 
if unsuccessful, foreign material can be 
removed from the stomach by gastrotomy. 
• GOTO—GDV should be corrected and 
future volvulus prevented with a gastropexy. 
• Intestinal obstruction—the full length of 
the intestinal tract should be examined and 
palpated; enterotomy should be performed to 
remove any luminal foreign material; if 
nonviable or perforated sections are present, 
resection and anastomosis should be 
performed. • Although intussusceptions can 
be percutaneously reduced, recurrence is very 
common; surgical reduction and/or resection 
with or without enteropexy is recommended.
• Parenteral broad-spectrum IV antibiotic 
therapy (ampicillin–sulbactam 30 mg/kg IV 
q8h with enrofloxacin 10 mg/kg IV q24h) should be initiated as soon as possible in 
patients with suspected GI obstruction. • In 
cases where GI ulceration is suspected or 
confirmed, use of a proton pump inhibitor is 
recommended (omeprazole or pantoprazole 
1 mg/kg q12h PO or IV, respectively). 
• Appropriate analgesia should be provided 
before, during, and after surgery; mu-agonist 
opioids (fentanyl 2–5  μg/kg/h IV as CRI or 
hydromorphone 0.1 mg/kg IV q4–6h) are 
recommended given their strong analgesic 
effect.
Prokinetic agents (e.g., metoclopramide, 
cisapride) must be avoided until obstruction 
• Use of antiemetic medications is 
contraindicated in patients with suspected GI 
obstruction. • Nonsteroidal anti-inflammatory 
drugs should not be used in patients with GI 
obstructions due to their adverse effects on 
the GI mucosa and renal function in patients 
that are not hemodynamically stable.
N/A
N/A
  FOLLOW-UP
• Dehiscence of gastrotomy and enterotomy 
sites can occur 3–5 days postoperatively; 
patients should be watched closely during this 
period for signs of lethargy, recurrence of 
vomiting, and fever. • Ventricular arrhythmias 
are documented in approximately 40% of 
GDV patients; in these cases, electrolyte and 
acid-base disturbances should be identified 
and treated, if present.
Efforts to prevent repeat ingestion of foreign 
bodies.
• Aspiration pneumonia. • Septic peritonitis. 
• Functional ileus.
• With rapid surgical intervention of 
uncomplicated cases of GI foreign bodies, 
prognosis is good (>95%); however, prognosis 
associated with septic peritonitis is 
significantly lower (50%); negative prognostic 
factors that have been identified include 
longer duration of clinical signs, presence of 
linear foreign body, and multiple surgical 
procedures. • With intestinal neoplasia, 
prognosis remains guarded to poor, with the 
exception of small cell lymphoma in cats; 
with gastric carcinoma, complete surgical 
excision is rarely attainable and intestinal carcinoma has high rate of metastasis at time 
of diagnosis; large cell GI lymphoma has 
relatively poor response rate to commonly 
used chemotherapy protocols, and median 
survival times in cats and dogs are 4–6 
months and 110 days, respectively.
N/A
See Signalment.
N/A
N/A
SYNONYMS
N/A
SEE ALSO
• Acute Abdomen.
• Pythiosis.
• CHG = chronic hypertrophic gastropathy.
• GDV = gastric dilation and volvulus.
• GOTO = gastric outflow tract obstruction.
Boag AK, Coe RJ, Martinez TA, Hughes D. 
Acid-base and electrolyte abnormalities in 
dogs with gastrointestinal foreign bodies. 
J Vet Intern Med 2005, 19:816–821.
Hayes G. Gastrointestinal foreign bodies in 
dogs and cats: a retrospective study of 208 
cases. J Small Anim Pract 2009, 
50:576–583.
Hobday MM, Pachtinger GE, Drobatz KJ, 
Syring RS. Linear versus non-linear 
gastrointestinal foreign bodies in 499 dogs: 
clinical presentation, management and 
short-term outcome. J Small Anim Pract 
2014, 55:560–565.
Steven L. Marks. 
available onlineGastrointestinal Obstruction  (continued)

Canine and Feline, Seventh Edition  561
GGestational Diabetes Mellitus
  OVERVIEW
Diabetes mellitus (DM), which occurs during 
mid to late gestation, most likely due to 
insulin resistance from increased progesterone 
and growth hormone production by the 
mammary glands.
• Middle-aged intact female dogs.
• Mean age—6 years.
• Nordic spitz breeds are overrepresented.
• Not reported in cats.
SIGNS
• Polydipsia.
• Ketosis.
• Late-term pregnancy.
• Diestrus.
• Exogenous progesterone supplementation.
  DIAGNOSIS
Acromegaly—affected bitches are listless and 
have increased abdominal size, increased 
interdental spaces, polyuria/polydipsia, 
weight gain, and excessive skin folds in the 
facial/neck areas.
CBC/Biochemistry/Urinalysis
• Glucosuria.
• Metabolic acidosis if ketonemic or 
ketonuric.
Other Laboratory Tests
Urine culture—urinary tract infections can 
contribute to insulin resistance.
Imaging
• Ultrasonography—assess fetal viability; 
deceased puppies may affect treatment 
decisions.
• Radiographs—determine fetal size and 
relative risk for dystocia.
Diagnostic Procedures
N/A
  TREATMENT
• Nonpharmacologic considerations—
management of gestational DM requires 
intensive fluid and insulin therapy. Continued glucose toxicity can destroy the 
pancreatic beta cells’ capacity to produce 
insulin, leading to permanent DM.
• Ovariohysterectomy is recommended. 
While the diabetes may resolve at the end of 
diestrus or after parturition, it will return on 
subsequent cycles and then has a greater 
potential to become permanent.
• Insulin—if ketosis not present, start at an 
insulin dose of 0.25 U/kg SC q12h of 
intermediate or long-acting insulin; will likely 
need to increase the dose to achieve glycemic 
control. If ketoacidosis is present, regular 
insulin (0.1–0.2 U/kg IM q4–6h) may be 
necessary to achieve initial glycemic control 
before switching to longer-acting insulin.
• Aglepristone—10 mg/kg SC days 1, 2, 9, 
and 17 from diagnosis. This medication is a 
progesterone receptor blocker, but does not 
affect progesterone levels. T reatment reserved 
for cases in which ovariohysterectomy is not 
possible or authorized by the owners.
N/A
  FOLLOW-UP
Care must be taken to avoid insulin overdose 
causing hypoglycemia during the immediate 
postpartum period (or the end of diestrus), 
because the speed at which insulin resistance 
resolves and exogenous insulin requirements 
decrease is unpredictable.
Ovariohysterectomy to remove source of 
progesterone.
Lack of prompt resolution of hyperglycemia 
may result in diabetes mellitus becoming 
permanent.
• Diabetes usually resolves at parturition or at 
the end of diestrus. More likely to be 
transient DM if pregnancy terminated, 
whereas insulin-treated bitches more likely to 
develop permanent DM.
• May abort the litter or have dystocia as a 
result of the effects of chronic hyperglycemia.
• Small, unthrifty puppies may result from an 
abnormal placental blood supply. Conversely, 
some fetuses in a hyperglycemic environment 
experience an abnormally increased growth rate (macrosomia). These puppies tend to be 
large, leading to dystocia.
Pregnancy
Older bitches are more likely to develop 
permanent DM.
N/A
May abort the litter or have dystocia as a 
result of the effects of chronic hyperglycemia. 
There is thought to be a genetic component, 
due to a breed predisposition. It is not advised 
to continue to breed affected individuals.
SEE ALSO
Diabetes Mellitus without Complication— 
Dogs.
Johnson CA. Glucose homeostasis during 
canine pregnancy: insulin resistance, ketosis, 
and hypoglycemia. Theriogenology 2008, 
70(9):1418–1423.
Author  Carla Barstow

562  Blackwell’s Five-Minute Veterinary Consult  
GGiardiasis
  BASICS
OVERVIEW
• Enteric infection of dogs and cats with 
protozoan parasite, Giardia duodenalis .
• Direct transmission by ingestion of cysts that 
are immediately infective when shed in feces.
• T rophozoites, motile (flagellated) organisms 
released from ingested cysts, attach to surface 
of enterocytes in small intestine with ventral 
sucking disc; move from site to site.
• Can cause small bowel diarrhea, but 
infection often asymptomatic.
SIGNS
• Clinical signs more common in young 
hosts; adults usually asymptomatic.
• Signs can be acute, transient, intermittent, 
or chronic.
• Malabsorption syndrome with soft, frothy, 
greasy, voluminous feces (diarrhea), usually 
with rancid odor.
• T ransmitted by ingestion of cysts from feces 
in/on food, water, environment, or fur.
• Indirect water-borne transmission most 
common; cool, moist conditions favor cyst 
survival.
• Higher risk of infection in puppies and 
kittens, in high-density populations, and in 
animals with compromised immunity.
  DIAGNOSIS
• Infectious and noninfectious causes of small 
bowel diarrhea, maldigestion, and 
malabsorption syndromes, especially 
pancreatic exocrine insufficiency or 
• In cats, differentiate from infection with 
Tritrichomonas foetus .
Generally within normal limits.
N/A
IMAGING
N/A
• Detection of Giardia  trophozoites, cysts, or 
antigen in feces.
• T rophozoites (15 × 8  μm) detectable in fresh 
feces (especially diarrheic feces) and in 
duodenal aspirates obtained by endoscopy; 
trophozoites identified on Diff-Quik® or 
Lugol’s iodine-stained fecal smear by teardrop 
shape with two prominent nuclei. T rophozoites identified in wet mount diluted in saline by 
“falling leaf” motility; flotation media may 
lyse trophozoites, interfering with accurate 
identification.
• Cysts, ~12  μm long, oval with 2–4 nuclei, 
shed intermittently; centrifugal flotation of 
fresh feces in zinc sulfate (specific gravity 
1.18) preferred method for identification of 
cysts. Three samples collected at 2–3-day 
intervals should be examined to detect >70% 
of infections; cysts become distorted 
(crescent-shaped) in sugar or other flotation 
solution with specific gravity >1.25; 
formalin–ethyl acetate sedimentation is useful 
in cases of steatorrhea.
• ELISA-based kits available for in-house 
detection of Giardia  antigen in feces have 
high sensitivity; kits should be used to 
confirm suspicious cases rather than for 
screening healthy animals; if clinical signs 
resolve, continued antigen testing not 
• PCR testing—commercial laboratories; 
studies have shown variable (usually poorer) 
sensitivity compared to other methods.
  TREATMENT
• Outpatient, unless debilitated or 
• Drug therapy should be combined with 
environmental cleaning and disinfection plus 
bathing of patient.
• Giardia  vaccines commercially available; 
efficacy is poor and vaccine not widely used.
• All extra-label.
• Fenbendazole—50 mg/kg PO q24h for 3 
days (dogs) or 5 days (cats); second course of 
treatment may be necessary.
• Metronidazole—20–22 mg/kg PO q12h 
for 5–8 days in dogs.
• Metronidazole benzoate—22–25 mg/kg 
PO q12h for 5–7 days in cats.
• Fenbendazole (50 mg/kg PO q24h) plus 
metronidazole (25 mg/kg PO q12h) for 5 
days—may provide better resolution and 
reduction in cyst shedding.
• Combination febantel, pyrantel pamoate, 
and praziquantel product—use for 3 days at 
label dose for Giardia .
• Metronidazole—efficacy reportedly 
50–67% in dogs; bitter taste; can cause 
anorexia, vomiting, vestibular signs.
• Albendazole (25 mg/kg PO q12h for 2 days 
in dogs or 5 days in cats) is effective but not recommended because it can be teratogenic 
and cause anorexia, depression, vomiting, 
ataxia, diarrhea, abortion, and 
myelosuppression.
  FOLLOW-UP
• Repeat fecal examinations to confirm 
efficacy of treatment and detect reinfection.
• Chronic infection can lead to debilitation.
• In North America, Giardia  is the most 
common intestinal parasite in humans. Dog 
and cat isolates are host specific, with little 
data to demonstrate transmission from pets to 
humans.
• Most Giardia  infections in humans are 
anthroponotic or originate from livestock.
• Zoonotic transmission from pets to 
immunosuppressed humans may occur.
Do not use albendazole in pregnant animals.
• https://capcvet.org
• https://www.cdc.gov/parasites/giardia
Bowman DD. Georgis’ Parasitology for 
Veterinarians, 9th ed. St. Louis, MO: 
Elsevier Science, 2009, pp. 89–91.
Uehlinger FD, Naqvi SA, Greenwood SJ, 
et al. Comparison of five diagnostic tests for 
Giardia duodenalis in fecal samples from 
young dogs. Vet Parasitol. 2017, 
244:91–96.
Authors  Matt Brewer and Katy A. Martin

Canine and Feline, Seventh Edition  563
GGingival Enlargement/Hyperplasia
  BASICS
OVERVIEW
• Enlargement of gingival tissue due to 
proliferation of its elements (abnormal 
multiplication or increase in the normal 
number of cells in normal arrangement).
• Probable familial tendency—boxers.
• Breed predilections—boxers, Great Danes, 
collies, Doberman pinschers, Dalmatians.
SIGNS
• Thickening and increase in height of 
attached gingiva and gingival margin—
sometimes completely covers tooth surface.
• Resultant formation of “pseudopockets”—
increase in pocket depth due to increased 
gingival height; not due to loss of attachment, 
unless untreated and progresses to concurrent 
periodontal disease.
• Gingival margin may be thickened in a 
labial to lingual direction, especially at 
incisors.
• Locally affected areas possible (shelties), but 
typically more generalized pattern found.
• Focally affected areas, other than the 
marginal gingiva, may develop hyperplastic 
areas due to chronic irritation, such as the 
“gum chewer’s lesion.” These areas should be 
evaluated for therapeutic need (excision).
• May form as protuberant masses (grape 
cluster) at gingival margins—biopsy necessary 
to rule out neoplasia.
CAUSES
Chronic inflammatory response to presence 
of bacteria in plaque associated with 
• Breed predilection (see Signalment).
• Chronic drug administration—
diphenylhydantoin, cyclosporine, 
nitrendipine, nifedipine, amlodipine.
  DIAGNOSIS
• Presumptive diagnosis based on clinical 
appearance, especially if generalized and 
found in breed with high predilection.
• Oral neoplasia—e.g., peripheral odontogenic 
fibromas; usually not generalized; sometimes 
osseous changes present.
• Oral papillomatosis—papilloma usually on 
mucosal surfaces.
• Operculum—seen in young animals during 
eruption phase of teeth; incomplete loss and/
or persistence of gingival tissue covering 
erupting tooth.• Chronic sublingual or buccal trauma with 
proliferation—“gum chewer’s lesion.”
IMAGING
Intraoral radiography—to rule out any 
underlying osseous changes (more common 
with epulides or tumors).
• Biopsy—focal area or areas that do not 
respond to standard therapy.
• Histopathology—to rule out neoplasia and 
other causes; histologic evaluation is only way 
to confirm.
  TREATMENT
Regular dental cleanings and homecare—to 
minimize effects of plaque and bacterial 
• Chronic, recurring problem that often 
needs repeated therapy.
• Encourage the highest level of home care 
and regular professional cleaning.
Gingivectomy (Excising Excess Tissue) 
and Gingivoplasty (Recontouring)
• To remove excess gingival tissue and return 
pocket depths to normal.
• Provide appropriate patient monitoring and 
support during anesthetic procedures.
• Regional and local anesthetic injections or 
topical gels.
• Periodontal probe—to determine depth of 
pseudopocket; can mark pocket depth on 
outside of pocket with end of probe to mark 
with a bleeding “dot.”
• Excise excess tissue and reshape gingival 
margin.
• Cold steel—sharp, stout scissors (crown 
and collar scissors) or scalpel blade.
• Connect dots made by probe with blade to 
approximate normal gingival margin or use 
scissors, following pocket depth to remove 
bulk tissue.
• T welve-fluted bur on high-speed 
handpiece—contour margin to feather angle; 
assists in hemostasis.
• Electrocautery or radiosurgery—use fully or 
partially rectified current; avoid damage to 
underlying bone or tissue.
• Laser—use appropriately and avoid damage 
to tooth and bone.
• Excessive thickness (incisor and canine 
region)—modified Widman technique; 
envelope flap to lift gingiva off tooth surfaces; 
excise tissue wedge to remove gingiva at inside 
of pocket to provide narrower width of 
attached gingiva; suture interdentally to 
secure gingiva; use digital pressure to 
reposition.• Tincture of myrrh and benzoin—use 
dropper; coat cut margins and dry; 4–5 layers.
• Hemostatic solutions—to aid in hemorrhage 
control as needed.
• Oral antimicrobials—chlorhexidine; zinc 
ascorbate gel.
• Postoperative pain management.
Patients on chronic administration of 
amlodipine, diphenylhydantoin or cyclosporine 
may be predisposed to hyperplastic changes. 
Dose reduction may decrease extent of gingival 
  FOLLOW-UP
• Postoperative comfort—give pain 
medication as needed.
• Regular examinations and professional 
cleaning and treatment—to avoid recurrence, 
which is common.
Regular professional cleaning, meticulous 
home care.
• Possible exacerbation of periodontal disease 
in pseudopockets if left untreated; deeper 
pockets are more susceptible to anaerobic 
• Excessive heat with electrosurgical 
treatment may result in damaged teeth 
(pulpitis, pulpal death) and alveolar bone.
• Good prognosis with regular care.
• Recurrence common.
Small Animal Dentistry, 2nd ed. Ames, IA: 
Blackwell, 2012 (for additional topics, 
including diagnostics and techniques).
NJ, Wiley-Blackwell, 2019.
Author  Heidi B. Lobprise

G
564  Blackwell’s Five-Minute Veterinary Consult  
GGlaucoma
  BASICS
• A group of diseases where elevated intra  ocular 
pressure (IOP) causes optic nerve and retinal 
degeneration with subsequent loss of vision.
• Diagnosis—IOP >20 mmHg (dogs) or 
>25 mmHg (cats) as determined by tonometry, 
with changes in vision or the appearance of the 
globe, optic nerve, and/or retina.
• Multifactorial disease where obstruction of 
aqueous humor outflow leads to increased 
IOP and optic nerve degeneration.
• Elevated IOP induces mechanical changes 
(stretching of sclera in lamina cribosa 
damages optic nerve axons) and vascular 
changes (decreased ocular perfusion causes 
ischemic damage to retina), resulting in 
ganglion cell death and optic nerve atrophy.
• Nervous.
GENETICS
• Primary angle-closure glaucoma (PACG; 
dogs)—complex trait with multiple genetic 
risk factors and uncertain mode of 
• Primary open-angle glaucoma (POAG; 
dogs)—monogenic ( ADAMTS10 ) and 
autosomal recessive.
• Primary congenital glaucoma (PCG; 
cats)—monogenic ( LTBP2 ) and autosomal 
recessive.
• Dogs—prevalence depends on breed; 
primary and secondary glaucoma are each 
listed as approximately 0.8% of all hospital 
admissions in the North American Veterinary 
Medical Database (NAVMDB).
• Cats—relatively uncommon; less than 
0.3% of diagnoses in NAVMDB.
Species
• Dog—primary and secondary common.
• Cat—primary rare; secondary more 
common (due to intraocular neoplasia or 
chronic uveitis).
• PACG—Alaskan Malamute, American 
cocker spaniel, Australian cattle dog, basset 
hound, Boston terrier, bouvier des Flandres, 
bullmastiff, Chinese Shar-Pei, chow chow, 
Dalmatian, Dandie Dinmont terrier, English 
cocker spaniel, English springer spaniel, 
flat-coated retriever, golden retriever, Great 
Dane, Labrador retriever, Newfoundland, 
poodle, Samoyed, Shiba Inu, shih tzu, 
Siberian husky, Welsh springer spaniel.• POAG—beagle, Norwegian elkhound, 
petit basset griffon Vendéen.
• PCG—Siamese cats.
• Other forms of primary glaucoma—
Burmese, Persian, Siamese cats.
• Primary (dogs)—any age; predominantly 
affects middle-aged (4–9 years).
• Secondary (cats)—usually affects older cats 
(>6 years).
Females suffer PACG compared to males at a 
ratio of 2 : 1.
SIGNS
All well-equipped small animal hospitals 
should have a tonometer.
• Dogs—owners may note pain (blepharospasm, 
tenderness about the head), serous to seromucoid 
ocular discharge, red or cloudy eye, dilated pupil, 
or altered vision; in chronic cases, globe 
enlargement may be apparent.
• Cats—signs are more subtle; eye may not 
appear painful, red, or cloudy; owners may 
note dilated pupil, vision changes, or enlarged 
globe.
Acute Primary
• High IOP (often >30 mmHg).
• Enophthalmos with elevated third eyelid.
• Episcleral injection.
• Diffuse corneal edema.
• Vision loss—may be detected by lack of 
menace response, dazzle reflex, and/or direct 
or consensual pupillary light reflex.
• Optic nerve may be normal or swollen and 
hyperemic.
Chronic (End Stage)
• High or normal IOP .
• Buphthalmos.
• Descemet’s streaks (Haab’s striae).
• Subluxated lens with an aphakic crescent.
• Optic nerve head atrophy will appear dark 
and cupped.
• Retinal atrophy detected by peripapillary or 
generalized tapetal hyper-reflectivity.
Secondary
• High IOP .
• Corneal edema.
• Aqueous flare.
• Iris changes (miosis or mydriasis, posterior 
synechia, iris bombé).
• Hyphema.
• Anterior lens luxation.
• Intumescent cataracts.
• Intraocular mass.CAUSES
• Congenital—severe dysgenesis/lack of 
formation of the iridocorneal angle.
• Primary—developmental iridocorneal angle 
anomalies that impede aqueous humor 
outflow.
• Secondary—obstruction of aqueous humor 
outflow by various mechanisms, e.g., uveitis 
(inflammatory cells or debris), anterior lens 
luxation (lens or attached vitreous), red blood 
cells, or neoplastic cells.
• Age.
• Breed.
• Chronic uveitis.
• Goniodysgenesis—developmental defect of 
• Lens luxation.
• Hypermature or intumescent cataracts.
• Hyphema.
• Intraocular neoplasia.
• Topically applied mydriatics—may 
precipitate acute glaucoma in predisposed 
animals.
• Primary glaucoma is bilateral and often 
asymmetric; the unaffected fellow eye is at 
risk for developing glaucoma.
  DIAGNOSIS
• See Red Eye.
• Conjunctivitis—normal IOP and pupil size 
with conjunctival hyperemia (diffuse, red 
discoloration) instead of episcleral vessel 
engorgement.
• Uveitis—initially low IOP with miotic 
pupil.
IMAGING
Ocular ultrasound—facilitates evaluation of 
eye with opaque ocular media; may identify 
cause of secondary glaucoma (lens luxation, 
intraocular tumor).
• Rebound or applanation tonometry—
essential for diagnosis of glaucoma.
• Gonioscopy—referral procedure that allows 
for evaluation of iridocorneal angle and assists 
with diagnosis of primary vs. secondary 
glaucoma.
• Systemic workup may be indicated in cases 
of secondary glaucoma due to chronic uveitis, 
hyphema, or intraocular neoplasia.
• Histopathologic evaluation is required for all 
eyes enucleated due to intractable glaucoma.
• Iridocorneal angle morphology assists 
diagnosis of primary vs. secondary glaucoma.
• Loss of retinal ganglion cells.
• Gliosis and “cupping” of optic nerve head.

Canine and Feline, Seventh Edition  565
GG  TREATMENT
• Acute—outpatient medical management vs. 
referral.
• Chronic—outpatient medical management 
vs. salvage surgical management.
• Warn client that primary glaucoma is a 
bilateral disease; more than 50% of dogs 
develop glaucoma in the other eye within 8 
months without prophylactic therapy.
• Warn client that up to 50% of dogs will be 
blind in the affected eye within the first year 
regardless of therapy.
• Acute, visual eyes (dogs)—referral surgical 
procedures aim to control IOP by decreasing 
aqueous humor production (transscleral or 
endoscopic cyclophotocoagulation), 
increasing outflow (gonioimplants), or both; 
medical treatment is still required long term 
to control IOP and inflammation.
• Blind, painful eyes (dogs and cats)—salvage 
procedures include enucleation, evisceration 
with intrascleral prosthesis (if no intraocular 
infection or neoplasia), and intravitreal 
gentamicin or cidofovir injection to minimize 
long-term medical therapy.
Use multiple agents to lower IOP into the 
normal range as quickly as possible in an 
attempt to salvage vision and maintain 
comfort. Topical hypotensive drugs have 
largely replaced systemic therapy due to 
higher efficacy and fewer side effects.
Acute Primary (Dogs)
• Prostaglandin analog—latanoprost 0.005% 
q12h. In emergency, apply one drop to 
affected eye, followed by another drop in 30 
min. Recheck IOP in 1–2 hours.
• Carbonic anhydrase inhibitor—dorzolamide 
2% q8h. Use in combination with latanoprost 
for long-term therapy.
• Topical corticosteroids—0.1% 
dexamethasone or 1% prednisolone acetate 
q12h. Use to control intraocular inflammation 
from initial hypertensive episode.
• ± Topical beta blocker—timolol maleate 
0.5% q12h. Minimal effect on lowering IOP 
in companion animals. Use as auxiliary or 
prophylactic medication.• ± Hyperosmotic agent—mannitol 1–2 g/kg 
IV over 20 min. In emergency, use to 
dehydrate vitreous humor and lower IOP if 
topical medications ineffective.
Secondary (Dogs and Cats)
• Identify and treat primary disease.
• Topical corticosteroids—to reduce 
inflammation if no ulcerative keratitis.
• Topical carbonic anhydrase inhibitors.
• ± Topical beta blockers.
• Topical atropine—do not use with glaucoma.
• Prostaglandin analogs/miotic agents—do 
not use with primary anterior lens luxation or 
uveitis; mostly ineffective in cats.
• Systemic absorption of topical beta blockers 
may cause bronchoconstriction and 
bradycardia in small dogs and cats.
• Hyperosmotic agents may initiate acute 
pulmonary edema in patients with cardiovascular 
disease or hypervolemia.
Concurrent administration of latanoprost 
with a topical nonsteroidal anti-inflammatory 
drug such as flurbiprofen 0.03% may 
decrease its hypotensive effect.
• Prostaglandin analogs—travoprost 0.004% 
q12h, bimatoprost 0.03% q12h.
• Carbonic anhydrase inhibitor—
brinzolamide 1% q8h.
• Beta blockers—levobunalol 0.5% q12h, 
betaxolol 0.5% q12h.
• Osmotic agents—hypertonic hydroxyethyl 
starch 6–7.5% (4 mL/kg IV over 15–20 min).
  FOLLOW-UP
• IOP—monitored often (weekly to 
monthly) after starting initial therapy, then 
q3-4 months long term. Client’s daily 
observation of comfort and vision is most 
important.
• Monitor for drug reactions.
• Primary—bilateral disease; recommend that 
a veterinary ophthalmologist examine the 
unaffected eye to determine its risk of 
developing glaucoma.
• Prophylactic therapy for the predisposed, 
unaffected eye delays onset of glaucoma—0.25% 
demecarium bromide (miotic) q12h, or 0.5% 
timolol maleate q12h, or 2% dorzolamide 
q8–12h.POSSIBLE COMPLICATIONS
• Chronic disease that requires constant 
medical treatment (even with surgical 
intervention).
• With medical treatment only—most 
patients ultimately become blind.
• Referral surgical treatment—better chance 
of retaining vision longer; most patients do 
not remain visual for more than 2 years after 
initial diagnosis.
• Secondary to lens luxation—may carry fair 
prognosis with referral for successful removal 
of luxated lens and postoperative medical 
therapy.
• Secondary to anterior uveitis—may carry 
fair prognosis with control of uveitis.
• All listed drugs may affect pregnancy.
• Primary and lens luxation cases—inherited; 
do not breed affected animals.
SEE ALSO
• Lens Luxation.
• Red Eye.
• PACG = Primary angle-closure glaucoma.
• POAG = Primary open-angle glaucoma.
• PCG = Primary congenital glaucoma.
• NAVMDB = North American Veterinary 
Medical Database.
Miller PE. The glaucomas. In: Maggs DJ, 
Miller PE, Ofri R, eds. Slatter’s 
Elsevier, 2018, pp. 279–305.
Pizzirani S, ed. Glaucoma. Vet Clin Small 
Anim 2015, 45(6): 1102–1378.
Author  Erin M. Scott
available online(continued)  Glaucoma

G
566  Blackwell’s Five-Minute Veterinary Consult  
GGlomerulonephritis
  BASICS
Glomerulonephritis (GN) is a term often used 
to describe proteinuria of glomerular origin; 
however, GN is immune-mediated inflammation 
within the glomerulus (immune complex 
glomerulonephritis [ICGN]). Because this can 
only be diagnosed from a renal biopsy, many 
noninflammatory conditions (glomerulosclerosis, 
amyloidosis, etc.) may be incorrectly labeled 
GN in patients who have not undergone 
evaluation via renal histology.
• Circulating antigen–antibody complexes 
become entrapped or antibodies can attach in 
situ to glomerular antigens or soluble antigens 
entrapped within the glomerular basement 
membrane; complement component C3 and/
or immunoglobulins (Ig) G, M, or A may be 
involved in complexes, which alter glomerular 
permeability and induce inflammation, 
causing proteinuria, nephron injury, fibrosis, 
and progressive loss of renal function.
• ICGN has several different morphologies 
depending on the location of immune-
complex deposition as well as the glomerular 
response to injury; membranoproliferative, 
membranous nephropathy, proliferative, IgA 
nephropathy, and minimal change disease are 
recognized ICGN in small animals.
• Inflammation and altered glomerular 
permeability result in proteinuria; subsequent 
oxidative damage and tubular obstruction 
cause renal injury, progressive nephron loss, 
and decreased glomerular filtration; azotemia 
and uremia may ensue.
• Hypercoagulability, hypoalbuminemia, and 
hypertension (HTN) are common 
• Renal/urologic—proteinuria is the initial 
symptom; both acute kidney injury (AKI) 
and chronic kidney disease (CKD) may occur 
secondarily.
• Cardiovascular—HTN is common; ascites 
and edema occur in nephrotic syndrome (NS); 
hypercoagulability and thromboembolism 
(TE).
• Endocrine/metabolic—hypercholesterolemia 
in NS.
GENETICS
Many breeds have inheritable glomerular 
disease leading to protein-losing nephropathy 
(PLN). Most are non-ICGN; however, several 
breeds are more frequently affected by GN 
Glomerular disease is present in most patients 
with kidney disease; however, not all are 
ICGN. Approximately 50% of dogs and cats that have undergone renal biopsy have 
ICGN. GN may be clinically silent and 
undiagnosed in many patients.
Worldwide
• Species—dog and cat.
• Breed predilections—American foxhound, 
Bernese mountain dog, Doberman pinscher, 
German shepherd, golden retriever, 
greyhound, Labrador retriever, Shetland 
sheepdog, and soft-coated wheaten terrier.
• Mean age and range—middle age (4–8 
years), although may occur at any time; cats 
often younger—mean 4 years.
• Predominant sex—dogs: none; cats: 
majority are male.
SIGNS
• Proteinuria caused by albuminuria is 
hallmark.
• Historical findings—nonspecific and include 
weight loss, muscle wasting, decreased appetite, 
lethargy, vomiting, and polyuria/polydipsia.
• Physical examination findings—may be 
normal; subcutaneous edema, peritoneal and/
or pleural effusion seen in NS; acute dyspnea 
and hypoxia may be present in pulmonary 
TE.
CAUSES
• Most patients have ICGN secondary to 
systemic infection or inflammation; many 
patients will not have an obvious trigger 
identified. * Infectious causes include 
rickettsial infection ( Borrelia , Ehrlichia , 
Anaplasma , Rocky Mountain spotted fever), 
babesiosis, bartonellosis, leishmaniasis, 
brucellosis, dirofilariasis, leptospirosis, systemic 
fungal infections, and hepatozoonosis.
• Inflammatory conditions include 
pancreatitis, polyarthritis, pyometra, and 
systemic lupus erythematosus; reactions to 
sulfonamides and vaccines is possible; 
paraneoplastic GN is uncommon.
Lyme-associated GN is a severe and progressive 
form of ICGN found in dogs with positive 
Borrelia  serology, but causation unknown. 
Labrador retrievers, golden retrievers, and 
several other breeds are more at risk.
  DIAGNOSIS
• Proteinuria—commonly occurs for reasons 
other than GN (see Proteinuria).
• Hypoalbuminemia—may result from 
decreased hepatic synthesis or protein-losing 
enteropathy.
• Azotemia—can also be due to AKI or 
CKD, which may not be caused by ICGN.CBC/BIOCHEMISTRY/URINALYSIS
• CBC may reveal thrombocytopenia, 
uncommonly leukocytosis; usually 
unremarkable.
• Hypoalbuminemia with normal or increased 
serum globulins; hypercholesterolemia seen in 
NS; azotemia may be present.
• Persistent proteinuria; some patients may 
be azotemic with preservation of urine 
• Urine protein : creatinine ratio (UPC) is 
gold standard test for diagnosing, quantifying, 
and monitoring proteinuria.
• Testing for underlying systemic infectious/
inflammatory causes should be performed as 
• Urine electrophoresis can be performed to 
fraction proteins by molecular weight to 
discriminate glomerular and tubular causes of 
• Blood pressure measurement should be 
IMAGING
ultrasound to evaluate for systemic disease.
• Renal biopsy is the only way to diagnose 
GN and determine the subtype; it 
characterizes fibrosis and chronicity, which 
may help predict recovery of renal function 
following treatment; percutaneous 
ultrasound-guided needle biopsy is 
commonly performed; small patients or those 
with congenital disease may benefit from a 
surgical wedge/punch biopsy; biopsy 
contraindications include uncontrolled 
hypertension, severe thrombocytopenia, and 
anticoagulant therapy.
• Histology using multiple stains, immuno -
fluorescence, and electron microscopy is 
required for definitive diagnosis of ICGN; 
biopsies should be submitted to a veterinary 
nephropathologist.
• Some patients are too unstable to have renal 
biopsy performed (thrombocytopenic, rapidly 
progressing azotemia, etc.); empiric immuno -
suppression should be given when ICGN is 
suspected in the absence of biopsy.
• Definitive diagnosis of ICGN depends on 
ultrastructural findings of electron-dense immune 
within glomeruli; positive immuno  fluorescence.
• Secondary changes to glomerular basement 
membrane, hypercellularity, and sclerosis.
  TREATMENT
• Many require inpatient therapy to correct 
hypovolemia, nausea, and anorexia; once

Canine and Feline, Seventh Edition  567
GGstabilized, patients can be managed as 
outpatient.
• Patients with AKI may require dialysis to 
treat severe uremia.
• Therapeutic plasma exchange may be 
IV crystalloids should be used judiciously. 
Hypervolemia is a common complication of 
ACTIVITY
No specific need for activity restriction; 
patients often have limited endurance.
DIET
• Ideal diets are protein and sodium 
restricted; prescription “renal” diets are most 
appropriate; home-prepared diets may be 
used after consultation with a nutritionist.
• Feeding tubes allow for delivery of 
supplemental nutrition and medication.
• Prognosis is guarded for azotemic patients; 
however, complete recovery may occur.
• Dialysis and plasma exchange may allow for 
more rapid control of disease and promote 
renal recovery.
• Avoid hypotension and renal hypoperfusion.
• Discontinue anticoagulant 1 week before 
biopsy.
• ICGN requires immunosuppression; 
mycophenolate (5–10 mg/kg q12h) is most 
commonly used; GI upset is most frequently 
observed side effect; peripheral edema is rare; 
short course of corticosteroids (prednisone 
2 mg/kg/day) can be used as mycophenolate 
may require 2 weeks to take effect.
• Cyclophosphamide (50 mg/m2 4 days/
week); sterile hemorrhagic cystitis and bone 
marrow suppression are side effects.
• Anti-proteinuric therapy includes 
inhibitors (enalapril/benazepril 0.5–1 mg/kg 
q12h) or angiotensin receptor blockers (ARB; 
telmisartan 1–3 mg/kg q24h); these have 
modest antihypertensive effects; begin at low 
doses and increase if response is inadequate; 
cautious use in severely azotemic patients.
• HTN treated with amlodipine (0.25–
0.8 mg/kg q24h) or telmisartan (1–3 mg/kg 
q24h).
• Systemic anticoagulation to prevent TE—
clopidogrel (1–4 mg/kg q24h) or aspirin (2–5 mg/kg q24h); newer direct factor X 
inhibitors may also be considered.
• ACE inhibitors and ARBs should not be 
used if patient is dehydrated or hypovolemic.
• Anticoagulation should be avoided in 
thrombocytopenic patients until platelet 
count is normal.
• ACE inhibitors and ARBs should be used 
cautiously in patients with serum creatinine 
>3.5, as they may exacerbate uremia; 30% 
increase in serum creatinine is generally 
tolerated, if uremic symptoms do not occur; 
hyperkalemia may occur at higher doses.
• Hypoalbuminemic patients poorly tolerate 
parenteral fluids; enteral hydration via feeding 
tube may be better tolerated.
• Immunosuppression increases risk of 
Dual therapy of ACE inhibitor and ARB 
increases risk of hyperkalemia.
• Corticosteroids not used for long-term 
management, but may be considered if other 
therapies cannot be afforded.
• Patients who fail initial immunosuppressive 
therapy may benefit from alternative 
  FOLLOW-UP
• Renal values, electrolytes, blood pressure, 
and urinalysis with UPC should be checked 
1–2 weeks after starting therapy; reduction in 
proteinuria may take 4–6 weeks; subsequent 
rechecks should occur every 1–4 months.
• Complete remission is obtaining UPC 
<0.5; partial remission is >50% reduction and 
therapeutic failure is <50% reduction in 
UPC.
• Normalization of serum creatinine expected 
with complete response to therapy; many 
patients will have partial remission with 
improved but not normal serum creatinine.
• Goal to obtain serum albumin >2.0 mg/dL.
• Repeat renal biopsy can document 
resolution of immune complexes and guide 
duration of immunosuppression.
Avoiding exposure to fleas and ticks may 
reduce risk of vector-borne infections causing 
ICGN; preventative therapies should be used.
• AKI or CKD.
• HTN.• NS.
• TE.
Guarded prognosis. Short survival has been 
reported for azotemic proteinuric dogs. 
Disease may progress despite therapy. 
Complete resolution of disease may occur 
with immunosuppression.
• HTN.
• Hypoalbuminemia.
• Hypercoagulability.
None
N/A
Patients with suspected genetic disease should 
not be bred.
SYNONYMS
• Glomerulonephropathy.
SEE ALSO
• GN = glomerulonephritis.
• HTN = hypertension.
• ICGN = immune complex 
glomerulonephritis.
• NS = nephrotic syndrome.
• PLN = protein-losing nephropathy.
Brown S, ed. Special issue: International 
Renal Interest Society consensus clinical 
practice guidelines for glomerular disease in 
dogs. J Vet Intern Med 2013, 27:S1–S75.
Littman MP . Protein-losing nephropathy in 
small animals. Vet Clin North Am Small 
Anim Pract 2011, 41(1):31–62.
Author  J.D. Foster
Consulting Editor  J.D. Foster(continued)  Glomerulonephritis

G
568  Blackwell’s Five-Minute Veterinary Consult  
G BASICS
OVERVIEW
• Glucagonoma is an uncommon pancreatic 
islet cell tumor originating from alpha cells, 
which secrete glucagon. They occasionally 
arise in extra-pancreatic locations (i.e., liver). 
Glucagonomas may secrete other hormones, 
such as gastrin, pancreatic polypeptide, and 
(rarely) insulin.
• Excess circulating glucagon activates glyco -
genolysis and gluconeogenesis and inhibits 
glycogenesis. This increases protein catabolism 
and lipolysis. Glucagon excess can inhibit 
erythropoiesis. The culmination of these 
biochemical changes results in hyperglycemia 
and occasionally diabetes mellitus (DM), 
hypoaminoacidemia, anemia, and weight loss. 
Glucagon can exert a secretory effect on the 
small intestine, leading to diarrhea.
• Glucagonomas may cause an overall 
decrease in plasma amino acid concentra-
tions, with epidermal protein depletion in the 
skin, leading to the classic dermatopathy 
associated with glucagonoma (necrolytic 
migratory erythema [NME]).
• Glucagonomas can affect numerous organ 
systems, including musculoskeletal, integu-
mentary, endocrine, gastrointestinal, nervous/
behavioral, and hepatobiliary.
• Dog—rare; older animals.
SIGNS
• The hallmark sign is NME, although this 
may be caused by glucagonoma or hepatocuta -
neous syndrome. NME has also been described 
in veterinary medicine as metabolic epidermal 
necrosis and superficial necrolytic dermatitis.
• Skin lesions include erythema, erosions, 
and crusting, generally located around 
mucocutaneous junctions (perineum, face, 
and genitalia), distal extremities, and foot  pads. 
Lesions are often pruritic with hyperkeratotic 
and painful footpads. In many cases, footpads 
are the only affected area.
• Other systemic signs include lethargy, polyuria, 
polydipsia, diarrhea, secondary pyoderma or 
yeast infection, anorexia, and weight loss.
Component of the multiple endocrine 
neoplasia syndrome.
 DIAGNOSIS
• Other diseases that produce skin lesions 
consistent with NME are nonspecific liver 
disease, hypoaminoacidemia, DM, and 
pancreatic tumors.• Other similar dermatopathies include 
pemphigus foliaceus, systemic lupus 
erythematosus, vasculitis, food dermatoses, 
vitamin A responsive dermatosis, and zinc 
deficiency dermatopathy.
• Mild–moderate hyperglucagonemia can 
result from nonglucagonoma diseases such as 
liver disease, pancreatic disease, chronic 
kidney disease, starvation, bacteremia, diabetic 
ketoacidosis, and hyperadrenocorticism.
• CBC—may be normal or show a normo-
cytic, normochromic anemia or mature 
neutrophilia.
• Biochemistry—may be normal or show 
mild elevations in liver enzyme activity or 
total bilirubin concentration, with mild 
hyperglycemia and hypoalbuminemia.
• Liver function tests (e.g., bile acid 
concentrations) are generally normal.
• Urinalysis—decreased urine specific gravity, 
glucosuria with DM.
• Plasma glucagon levels are generally 
extremely elevated ( >1,000 pg/mL); however, 
normal to mild elevation does not rule out 
glucagonoma.
• Plasma amino acid concentrations are 
generally severely reduced and are thought 
to be associated with the development of 
NME.
• Plasma zinc concentration is generally 
reduced and also thought to be associated 
with the development of NME.
• Serum fructosamine may be elevated in 
patients with DM.
IMAGING
• Ultrasonography—to detect pancreatic 
glucagonomas, peripancreatic metastases, and 
hepatic metastases; however, ultrasound was 
normal in 4/9 dogs with glucagonoma. A 
honeycomb pattern has been described in the 
liver of patients with NME.
• CT, MRI, PET scans, selective visceral 
angiography, and somatostatin receptor 
scintigraphy (octreoscan and radioiodinated 
MIBG) are used to detect glucagonoma in 
humans.
• Increased serum glucagon and clinical 
signs consistent with NME are indicative 
of glucagonoma, but the definitive 
diagnosis can only be made by biopsy, 
histopathologic examination, and immu -
nohistochemical documentation of 
glucagon expression.
• Immunohistochemical assays for other 
pancreatic and gastrointestinal hormones may 
also be performed.
• Skin biopsies taken from glucagon-associ-
ated NME lesions typically exhibit severe superficial to mid-epidermal edema, diffuse 
parakeratotic hyperkeratosis, and irregular 
epidermal hyperplasia.
• Biopsies taken from the primary 
glucagonoma (and/or metastases) typically 
exhibit pleomorphic islet cells with fine 
cytoplasmic granules and occasional 
mitoses with immunohistochemical 
glucagon (and often other secretory 
hormone) expression.
 TREATMENT
• Surgical excision of nonmetastatic primary 
pancreatic glucagonoma is the best chance for 
cure. There is a high rate of postoperative 
morbidity and mortality in dogs, often 
secondary to pancreatitis. Glucagonoma 
syndrome reported in people is associated 
with thromboembolic disease.
• Combined debulking (primary tumor and/
or metastases) and octreotide therapy can 
temporarily resolve skin lesions and provide 
relief of clinical signs.
• If surgery and/or octreotide therapy are not 
possible, symptomatic palliative therapies 
may be beneficial and include high-protein 
diet with egg whites (approximately two to 
four egg whites/day for a 25 kg dog), zinc 
supplementation (beneficial even in the face 
of normal serum zinc concentration), and 
fatty acid supplementation.
• IV amino acid therapy may be beneficial in 
patients with NME.
• Secondary bacterial and/or yeast skin 
infections are common and should be 
appropriately treated.
• Concurrent DM should be treated.
• Octreotide—somatostatin analogue that 
inhibits conversion of preproglucagon to 
glucagon; may be beneficial in patients with 
unresectable or metastatic glucagonoma. Side 
effects reported in humans include injection 
site pain, vomiting, diarrhea, and cholestasis. 
A safe and effective dosage has not been 
reported in dogs; however, 10–20  μg/dog SC 
q8–12h has been used, and a one-time dose 
of 50  μg/dog SC is reported to be safe in 
healthy dogs. Octreotide can be difficult to 
obtain.
• Chemotherapeutics in humans with 
glucagonoma include doxorubicin and 
streptozotocin, although efficacy may be 
limited. The use of streptozotocin as an 
islet-cell lytic agent has been reported in a 
small number of dogs with insulinoma, but 
not in dogs with glucagonoma.Glucagonoma

Canine and Feline, Seventh Edition  569
GG• Glucocorticoids may improve the pruritis 
of NME skin lesions, but are not 
 recommended for use in glucagonomas as 
they are likely to exacerbate hyperglycemia 
associated with secondary DM.
• IV amino acids (500 mL of essential amino 
acids added to saline or lactated Ringer’s 
solution over 12h, or 10% amino acid 
solution 24 mL/kg over 8–12h) have resulted 
in variable improvement in NME skin lesions 
in dogs. T reatments may be repeated every 
1–2 weeks if effective until clinical signs abate 
or resolve.
• Sulfur/salicylic acid–based shampoos or 
very mild shampoos may help remove crusts, 
soften skin, and improve pain and pruritus 
associated with footpad or skin lesions.
• Oral zinc sulfate (10 mg/kg/day PO), zinc 
methionine (2 mg/kg/day PO), or zinc 
gluconate (3 mg/kg/day PO) may be 
• Supplementation with oral fatty acids 
(80 mg/kg PO) may also be of benefit.
Glucocorticoids may exacerbate hyperglyce-
mia if DM is present. FOLLOW-UP
• Serial blood work should be performed 
postoperatively to confirm that hyperglucagon -
emia (and any other abnormalities) is resolving.
• Strong considerations should be given to 
serial ultrasounds and chest radiographs to 
monitor for regrowth or metastasis.
• Thromboembolic disease.
• DM.
• Prognosis is considered poor in dogs.
• T ransient improvement in skin lesions and 
clinical signs may be noted in patients treated 
with octreotride and amino acids.
• One cat had a survival time of 11 months 
following surgery.
SEE ALSO
• Superficial Necrolytic Dermatitis.ABBREVIATIONS
• NME = necrolytic migratory erythema.
Allenspach K, Arnold P , Glaus T, et al. 
Glucagon-producing neuroendocrine 
tumour associated with hypoaminoacidemia 
and skin lesions. J Small Anim Pract 2000, 
41:402–406.
Asawaka MG, Cullen JM, Linder KE. 
Necrolytic migratory erythema associated 
with a glucagon-producing primary hepatic 
neuroendocrine tumor in a cat. Vet Dermal 
2013, 24:466–469.
Chastain MA. The glucagonoma syndrome: a 
review of its features and discussion of new 
perspectives. Am J Med Sci 2001, 
321(5):306–320.
Feldman EC, Nelson RW. Gastrinoma, 
glucagonoma and other APUDomas. In: 
Canine and Feline Endocrinology and 
Reproduction, 3rd ed. St. Louis, MO: 
Saunders, 2004, pp. 654–655.
Langer NB, Jergens AE, Miles KG. Canine 
glucagonoma. Compend Contin Educ Pract 
Vet 2003, 25(1):56–63.
Consulting Editor  Patty A. Lathan(continued)  Glucagonoma

G
570  Blackwell’s Five-Minute Veterinary Consult  
GGlucosuria
  BASICS
Glucosuria is detected via routine laboratory 
testing, most commonly with reagent test 
strips. Persistent glucosuria is an abnormal 
finding.
• Glucose is a small molecule that is freely 
filtered through the glomerulus into the 
ultrafiltrate. • Glucose is actively reabsorbed 
in the proximal renal tubule by a sodium–
glucose co-transport system. Physiologic levels 
of filtered glucose are mostly reabsorbed, 
leaving excreted levels too low to detect using 
Hyperglycemic Glucosuria
• Glucosuria will be present when blood 
glucose concentration exceeds renal tubular 
epithelial transport maximum. This varies by 
species, with dogs typically above 180 mg/dL 
and cats typically above 280 mg/dL. • If 
hyperglycemia is present, determine whether 
glucosuria transient or persistent.
Transient
• Physiologic—usually transient and 
associated with release of endogenous “stress” 
hormones (catecholamines, glucagon, 
corticosteroids); especially common in cats. 
Serum may be normoglycemic or hyperglycemic 
at urine collection because different 
concentrations of glucose excreted in urine 
over time equilibrate in bladder. 
• Pharmacologic—may occur following 
administration of glucose-containing 
solutions (e.g., dextrose); administration of 
drugs (glucocorticoids, growth hormone, 
thiazide diuretics, morphine, epinephrine) 
may also result in hyperglycemia and 
glucosuria. • Toxic—ethylene glycol. 
• Pathologic—possible with acute 
Persistent
Pathologic conditions that can result in 
persistent glucosuria (due to hyperglycemia) 
include diabetes mellitus, hyperadrenocorticism, 
acromegaly, extreme stress, hyperthyroidism 
in cats.
Normoglycemic Glucosuria
Impaired renal proximal tubular epithelial cell 
reabsorptive capacity.
Primary glucosuria—Scottish terriers; Fanconi 
syndrome: basenji dogs; also sporadic in 
Norwegian elkhounds, Shetland sheepdogs, 
miniature schnauzers, Labrador retrievers, 
border terriers, whippets, Yorkshire terriers, 
and mixed-breed dogs; decreased reabsorption 
of glucose, amino acids, and phosphorus plus 
decreased secretion of hydrogen ions.Acquired
• Fanconi syndrome due to toxicity such as 
heavy metal poisoning (e.g., lead, mercury, 
copper, copper associated hepatitis) or dried 
chicken treats made in China, drugs (e.g., 
gentamicin, cephalosporins, outdated 
tetracycline, cisplatin, streptozotocin), 
chemicals (Lysol, maleic acid), other 
miscellaneous causes. • Acute renal failure 
with significant tubular lesions.
• Renal—normoglycemic patients have 
abnormal renal tubular epithelial cell 
function; dogs with Fanconi syndrome may 
develop metabolic acidosis and chronic 
kidney disease (CKD) with secondary 
multisystem involvement; glucosuria 
predisposes to bacterial urinary tract 
infection. • Endocrine—hyperglycemic 
patients may have diabetes mellitus and/or 
hyperadrenocorticism. • Liver—copper 
associated hepatitis; centrilobular hepatitis 
with copper accumulation.
• Adult dogs and cats develop persistent 
hyperglycemic glucosuria due to adult-onset 
diabetes mellitus. • Dogs with congenital 
Fanconi syndrome typically develop clinical 
disease due to defective reabsorption of 
glucose and amino acids at 4–5 years of age; 
no sex predilection. • Familial renal tubular 
disorders have been reported (see Patho -
physiology). • Primary renal glucosuria 
(Scottish terriers) may be recognized at early 
age as incidental finding. • Copper 
associated hepatitis with acquired Fanconi 
syndrome (Labrador retrievers). • Dogs 
(any breed or age) fed dried chicken treats 
made in China.
SIGNS
Clinical signs variable depending upon 
primary cause.
• Persistent glucosuria results in polyuria 
(osmotic diuresis), leading to compensatory 
polydipsia. • Glucosuria predisposes to 
urinary tract infections; clinical signs 
associated with upper and/or lower urinary 
tract infection. • Breed and therapeutic 
history (see Pathophysiology) are important.
• Patients with hyperglycemic glucosuria may 
exhibit systemic signs; see diabetes mellitus 
chapters. • Patients with normoglycemic 
glucosuria may have normal body functions. 
• Dogs with Fanconi syndrome may develop 
signs of metabolic acidosis, electrolyte 
abnormalities, and CKD.
CAUSES
Hyperglycemic Glucosuria Transient
• Physiologic—stress; common in cats. 
• Pharmacologic—see Pathophysiology.Persistent
• Diabetes mellitus; insulin deficiency or 
resistance. • Hyperadrenocorticism; insulin 
resistance. • Acute pancreatitis; insulin 
deficiency or resistance. • Less common causes 
include pheochromocytoma, acromegaly, 
hyperglucagonemia, hyperpituitarism, 
hyperthyroidism, and chronic liver failure (due 
to failure to metabolize glucagon).
• Primary renal glucosuria (Scottish terrier). 
• Fanconi syndrome. • Congenital diseases 
may be associated with renal dysfunction 
(Norwegian elkhound).
Acquired
• Acute kidney injury associated with 
proximal tubular dysfunction. • Fanconi 
syndrome. • CKD (rare).
Vary with underlying causes.
  DIAGNOSIS
• Persistent hyperglycemic glucosuria in 
fasted patients is frequently associated with 
endocrinopathies (diabetes mellitus, 
hyperadrenocorticism). • Acute pancreatitis. 
• Renal tubular reabsorptive dysfunctions 
cause normoglycemic glucosuria. • Stressed 
patients exhibit mild transient hyperglycemia 
and glucosuria.
Screening Tests
Normally negative (urine glucose 
concentration below detection).
Glucose Oxidase T ests
• Reagent strips use glucose oxidase method 
that is specific for glucose; positive values 
occur with urine glucose concentrations 
greater than 100 mg/dL. • Methodology is a 
two-step enzymatic process—glucose oxidase 
catalyzes glucose and produces gluconic acid 
and hydrogen peroxide; peroxidase catalyzes 
reaction of hydrogen with chromagen to 
produce color change on reagent pad; the test 
is time dependent, which varies with 
manufacturer; pigmenturia can complicate 
color interpretation. • False negatives can be 
seen with ascorbic acid, exposure to formalin, 
ketonuria, marked bilirubinuria, highly 
concentrated urine, and refrigerated urine 
samples that have not been warmed to room 
temperature prior to performing the test. 
• False positives can be seen with exposure to 
oxidizing agents such as hydrogen peroxide 
or chlorine bleach (most commonly with 
samples obtained from table top or floor). 
• Specific for glucose; more sensitive

Canine and Feline, Seventh Edition  571
GG(~40–100 mg/dL) than copper reduction 
methods.
 Glucose O(air) H0
glucur onicacid H0
H022
oxidas e 2
22horser aadish
peroxidase2H0 O(nascen toxygen)
Oc olorindicator oxidized color 
change  complex
Copper Reduction T ests
• Not specific for glucose; less sensitive 
(250 mg/dL) and higher detection limit than 
glucose oxidase methods; more often used in 
human medicine, but can be used in 
veterinary medicine to verify questionable 
reagent strip result. • Testing method uses 
copper, which reacts with reducing substance 
(e.g., glucose, fructose, lactose, etc.) to 
produce cuprous oxide and cuprous 
hydroxide, which results in color change. 
• Results are semiquantitative and reported as 
negative, approximately 250 mg/dl, approxi -
mately 500 mg/dL, approximately 750 mg/dl, 
approximately 1000 mg/dL, or approximately 
2000 mg/dL. • Less affected by pigmenturia; 
false positives can be seen with cephalosporins, 
formaldehyde, reactions with other sugars, 
and high concentrations of ascorbic acid.
Cupricionsglucose
cuprous io nsoxidized glu(blue)alkali
ccose
(orangered)-  
Confirmatory Tests
Hexokinase or glucokinase dehydrogenase 
tests using automated chemistry analyzer may 
be used to confirm presence or absence of 
glucose when unexpected results or 
pigmented urine encountered.
See Screening Tests.
Results
Yes
• Hyperglycemia with glucosuria and ketonuria 
indicates diabetic ketoacidosis; persistent 
hyperglycemia and glucosuria with appropriate 
clinical signs support diabetes mellitus. • Dogs 
with pancreatitis may have leukocytosis, fever, abdominal pain and effusion, elevations in 
pancreatic specific enzymes, and characteristic 
ultrasonographic abnormalities. • Dogs with 
markedly increased serum alkaline phosphatase 
activity, hyperglycemia, glucosuria (also hyper -
cholesterolemia, hypertriglyceridemia) should 
be evaluated for hyperadrenocorticism. • Mild 
glucosuria with transient hyperglycemia is likely 
physiologic in stressed patients.
• Hyperglycemic glucosuria—conduct 
appropriate screening test if hyperadrenocorticism 
suspected. • Normoglycemic glucosuria—
measurement of phosphorus, glucose, and 
amino acid concentrations in timed urine 
samples may help differentiate Fanconi 
syndrome and primary renal glucosuria; also 
evaluation of hepatic function for acquired 
Fanconi syndrome due to copper associated 
hepatitis.
IMAGING
Ultrasonography aids in diagnosis of 
hyperadrenocorticism and pancreatitis.
  TREATMENT
• Discontinue any drugs associated with 
acquired renal tubular transport defects. 
• T reatment varies with cause; see chapters 
related to specific causes.
• Hyperglycemic glucosuria—treat diabetes 
mellitus with insulin. • Normoglycemic 
glucosuria—no treatment required for 
tubular transport disorders unless metabolic 
acidosis, electrolyte abnormalities, or hepatic 
abnormalities present (e.g., Fanconi 
Patients with diabetes mellitus should not be 
given diabetogenic drugs such as corticosteroids 
or dextrose-containing fluids.
  FOLLOW-UP
Variable, depending upon underlying condition.POSSIBLE COMPLICATIONS
• Persistent glucosuria predisposes to 
development of bacterial urinary tract 
infections (cystitis, ascending pyelonephritis). 
• Osmotic diuresis with obligatory polyuria 
results in polydipsia, necessitating access to 
water to prevent dehydration.
Growth hormone–secreting pituitary tumors 
in older cats (especially male) may induce 
diabetes mellitus (insulin resistant).
• Urinary tract infections. • CKD. 
• Diabetic retinopathy or cataracts. • Copper 
associated hepatitis.
Excess progesterone secretion in intact female 
dogs may induce diabetes mellitus (insulin 
resistant).
SEE ALSO
Diseases.
• Diabetes Mellitus without Complication— 
Cats.
• Diabetes Mellitus without Complication—  
Dogs.
pp 257–264.
2012, pp. 38–40.
Stockham S and Scott M. Fundamentals of 
Veterinary Clinical Pathology, 2nd ed. Ames, 
IA: Wiley-Blackwell, 2008, pp. 462–464.
of Cheryl L. Swenson and Carl A. Osborne.(continued)  Glucosuria

572  Blackwell’s Five-Minute Veterinary Consult  
G BASICS
OVERVIEW
A rarely confirmed, inherited, intestinal 
disease in which sensitivity develops to 
dietary gluten (present in wheat) and similar 
proteins present in related grains (i.e., rye 
and barley). In affected dogs, the enteropa -
thy is characterized by partial villous 
atrophy, reduced brush border enzyme 
expression, lymphocytic infiltration of the 
intestinal mucosa, and goblet cell hyperpla -
sia; changes that are reversed by feeding a 
gluten-free diet.
• Irish setter breed—the line of affected 
setters originally described in the UK has 
been bred out.
• Signs develop in young dogs, but are 
modulated by the age of first exposure to gluten.
• Genetic transmission of gluten sensitive 
enteropathy is likely under the control of a 
single major autosomal recessive locus.
• Gluten enteropathy has been suspected but 
not proven in other dog breeds and cats.
SIGNS
• Poor weight gain (or weight loss).
• Mild small intestinal diarrhea that can be 
intermittent.
The enteropathy and clinical signs are 
triggered by gluten-containing diets. 
Abnormal mucosal permeability precedes the 
development of signs, implying there is 
abnormal entry of gluten across the mucosal 
barrier. Gluten is then either directly toxic to 
the intestinal mucosa or induces an immune-
mediated reaction. An analogous condition in 
humans (celiac disease) is characterized by the 
presence of antibodies cross-reacting to gluten 
and tissue transglutaminase, but they have 
not been tested for in affected setters. These 
antibodies have been demonstrated in Border 
terriers with gluten-sensitive dyskinesia.
 DIAGNOSIS
• Canine chronic enteropathy—food-respon-
sive enteropathy, inflammatory bowel disease.
• Infectious diseases such as Giardia , hook -
worms, and roundworms.
• Metabolic abnormalities.
• Biochemistry can be unremarkable or may 
show panhypoproteinemia.
• CBC may show eosinophilia.OTHER LABORATORY TESTS
• Serum folate concentrations are subnor -
mal in some patients, reflecting 
malabsorption.
• Other tests are recommended to rule out 
other differentials, such as fecal flotation to 
rule out enteric parasites and serum trypsin-
like immunoreactivity (TLI) to rule out 
exocrine pancreatic insufficiency.
• Serum TLI and cobalamin concentrations 
are usually unremarkable.
IMAGING
Only useful to rule out other conditions.
Intestinal biopsy specimens obtained via 
endoscopy or laparotomy may be helpful, 
but proof of gluten sensitivity requires 
histologic resolution in biopsies repeated 
following a clinically successful gluten-free 
diet trial.
• Histologic examination of jejunal biopsy 
specimens from affected dogs reared on a 
wheat-containing diet reveals partial villus 
atrophy and accumulation of intraepithelial 
• Jejunal abnormalities improve following 
gluten withdrawal, but recur with gluten 
challenge.
 TREATMENT
T reatment is on an outpatient basis. Avoid 
diets containing gluten (wheat, rye, barley, 
triticale, brewer’s yeast, and wheat starch) for 
the life of the animal.
Folate (0.5–2 mg PO q24h for 2–4 weeks) if 
serum folate concentration is markedly 
subnormal ( <4 μg/L).
N/A
 FOLLOW-UP
Consider periodic assay of serum folate 
(q6–12 months) if initially decreased.
• TLI = trypsin-like immunoreactivity Suggested Reading
Cave N. Adverse food reactions. In: 
Elsevier, 2013, p. 403.
Hall EJ, Day MJ. Diseases of the small 
intestine. In: Ettinger SJ, Feldman EC, 
Côté E, eds., Textbook of Veterinary 
Elsevier, 2017, p. 1547.
Lowrie M, Garden OA, Hadjivassiliou M, 
et al. Characterization of paroxysmal 
gluten-sensitive dyskinesia in Border terriers 
using serological markers. J Vet Intern Med 
2018, 32(2):775.
Krysta DeitzGluten Enteropathy in Irish Setters

Canine and Feline, Seventh Edition  573
GGlycogen Storage Disease
  BASICS
OVERVIEW
• Also known as glycogenosis—rare inherited 
disorders of defective or deficient enzyme 
activity governing glycogen metabolism. 
• Tissue glycogen accumulation—leads to 
organ enlargement and dysfunction; may 
affect liver, heart, skeletal muscle, kidney, and 
CNS. • Impaired hepatic glycogenolysis—
leads to symptomatic hypoglycemia (neuro­
glycopenia). • Classification—based on 
enzymatic defect and primary organ(s) 
involvement: more than 12 types in humans, 
4 types in dogs (Ia, II, III, and VII), 1 type in 
cats (IV).
• Clinical signs manifest in juveniles—may 
be days to months after birth. • Type Ia (von 
Gierke’s disease)—Maltese puppies; autosomal 
recessive mutation of glucose ­6­phosphatase 
gene (gene symbol: G6PC ). • Type II 
(Pompe’s disease)—Swedish Lapland, Finnish 
and Swedish Lapphund dogs; onset by 6 
months of age; autosomal recessive, single 
mutation in acid α­glucosidase (gene symbol: 
GAA ). • Type III (Cori’s disease)—young 
female German shepherds, curly ­coated 
retrievers; autosomal recessive mutation in 
glycogen debranching enzyme (gene symbol: 
AGL). • Type IV (Andersen disease)—
Norwegian forest cats; may be stillborn or 
fade shortly after birth; may manifest signs at 
5–7 months with progressive neurologic 
decline; autosomal recessive mutation in 
glycogen branching enzyme (complex 
rearrangement mutation; gene symbol 
GBE1 ). • Type VII (Tarui disease)—English 
springer, American cocker, whippets, mixed 
breeds; PFK (M ­PFK) muscle isoform single 
missense mutation; different missense 
mutation in wachtelhunds; adult dogs, no sex 
predilection. • Autosomal recessive 
inheritance—Maltese, Lapland, Lapphund, 
English springer spaniels, Norwegian forest 
cats, other M ­PFK affected breeds; also 
suspected in German shepherds.
SIGNS
• Depend on enzymatic defect. • Type Ia 
(Maltese puppies)—failure to thrive; mental 
depression; hypoglycemia; abdominal 
distention; hepatomegaly; death or euthanasia 
by 60 days of age. • Type II (Lapland dogs)—  
vomiting and regurgitation related to 
megaesophagus; progressive muscle weakness; 
cardiac changes; death before 2 years of age. 
• Type III (German shepherds, curly ­coated 
retrievers)—depression; weakness; stunted; 
abdominal distention from hepatomegaly; 
mild hypoglycemia, high liver enzymes and 
creatine kinase. • Type IV (Norwegian forest 
cats)—perinatal death common; intermittent 
fever; generalized muscle tremors; muscle atrophy, weakness progressing to tetraplegia; 
sudden death from myocardial degeneration 
and terminal dysrhythmia; glucose 
administration can enable cats to survive to 
adulthood. • Type VII (English springer 
spaniels)—compensated hemolytic anemia; 
episodic weakness, exercise ­induced with 
intravascular hemolysis; hemoglobinuria;  
one patient with a progressive myopathy at 
11 years of age: no liver effect.
Deficiencies
• Type Ia—glucose ­6­phosphatase. • Type 
II—acid ­α–glucosidase. • Type III—amylo ­
1,6­glucosidase. • Type IV—glycogen 
branching enzyme ( α­1,4­d­glucan).  
• Type VII—phosphofructokinase.
  DIAGNOSIS
• High index of suspicion for diagnosis. 
• Breed affiliation—familial history. 
• Differentiate other causes of juvenile 
hypoglycemia—malnutrition; endoparasitism; 
transient fasting hypoglycemia; portosystemic 
vascular anomaly. • Other causes of muscular 
weakness—infectious diseases; endocrinopathy; 
immune ­mediated causes; hypokalemia; other 
neuromyopathies.
• Types I and III—hypoglycemia. • Type 
I—lactic acidemia, increased: cholesterol, 
triglycerides, uric acid. • Type VII—anemia; 
reticulocytosis; pigmenturia, no hepatic 
effects.
Genetic testing—type I: in Maltese dogs, type 
II: in Lapland and Lapphund dogs, type III: in 
curly ­coated retrievers, type IV: in Norwegian 
forest cats, type VII: in breeds listed previously 
and in vitro erythrocyte testing.
IMAGING
• Type II—thoracic radiography; cardiomegaly 
and megaesophagus. • Types Ia and III—
abdominal radiography; hepatomegaly.  
• Abdominal ultrasonography—hepatomegaly, 
hyperechoic parenchyma consistent with 
hepatic glycogen accumulation. • Types II 
and IV—echocardiography may reveal 
cardiac changes.
• Tissue enzyme analysis and glycogen 
determination. • Electromyography—
depends on disorder. • ECG—depends on 
disorder.
• Genetic testing.
• Type Ia—emaciation; massive hepatomegaly 
due to hepatocyte glycogen and lipid 
vacuolation and similar change in renal tubular epithelium. • Type II—glycogen 
accumulation in skeletal, smooth, and cardiac 
muscle. • Type III—hepatomegaly due to 
hepatic glycogen accumulation; also in 
skeletal muscle. • Type IV—generalized 
muscle atrophy; glycogen accumulation: 
skeletal muscle, CNS, and peripheral nervous 
system. • Type VII—polysaccharide deposits 
in skeletal muscle.
  TREATMENT
• Supportive care. • Types I and III—may 
require IV/SC dextrose for management of 
hypoglycemic crisis; long ­term management 
usually futile. • Gene therapy with adeno ­
associated virus vector experimentally for  
type 1a dogs resulted in survival.
Diet
Control hypoglycemia (types I and III) with 
frequent feedings of a high ­carbohydrate diet 
until diagnosis is confirmed; glucose solutions 
usually used.
• Advise that specimens be submitted for 
genetic/enzyme characterizations. • Discuss 
known mechanisms of inheritance to modify 
breeding programs.
N/A
  FOLLOW-UP
• Monitor for hypoglycemia. • Cull parents 
from breeding programs. • Prognosis—poor; 
most patients with glycogen storage disorders 
causing hypoglycemia and hepatomegaly and 
stunted growth die or are euthanized owing 
to progressive deterioration.
SEE ALSO
• Lysosomal Storage Diseases. 
• Mucopolysaccharidosis. • Portosystemic 
Vascular Anomaly, Congenital.
Walvoort HC. Glycogen storage disease  
type II in the Lapland dog. Vet Q 1985, 
7:187–190.

G
574  Blackwell’s Five-Minute Veterinary Consult  
G BASICS
• Glycogen-type vacuolar hepatopathy 
(VH)—reversible hepatocellular cytosolic 
vacuolation.
• Reflects many primary disorders 
including glucocorticoid treatment, 
hyperadrenocorticism, atypical adrenal 
hyperplasia (sex hormone hyperplasia), 
chronic systemic illnesses (inflammatory, 
neoplastic), and rarely congenital glycogen 
storage disorders.
• Typified by high alkaline phosphatase 
(ALP) activity—usually without hyperbiliru-
binemia or hepatic insufficiency.
• Similar but remarkably severe VH in 
hepatocutaneous disease; may reflect chronic 
phenobarbital administration.
• Glycogen VH may coexist with cytosolic 
lipid vacuolation—comparatively rare in 
dogs, but may associate with idiopathic 
hyperlipidemia, diabetes mellitus, hypothy-
roidism, and rare inborn errors of glycogen/
lipid metabolism.
• Glucocorticoids—induce reversible increase 
in hepatocyte glycogen within 2–3 days; 
injectable or reposital drug induces most 
severe VH compared to PO or topical (ocular, 
cutaneous, aural) routes.
• Cell expansion—causes hepatomegaly, 
ballooning degeneration leads to parenchymal 
collapse; when severe, nodularity grossly 
mistaken for cirrhosis.
• Variable response to glucocorticoids among 
dogs relates to drug type; route; dose; 
treatment duration; individual sensitivity—
VH may follow low-dose, short-term oral 
• VH may reflect stress response, 
cytokines, or acute-phase response initiated 
by nonhepatic systemic disorders or 
neoplasia (especially lymphoma), without 
exogenous glucocorticoid exposure or 
adrenal disease.
• VH common in dogs with gallbladder 
mucocele.
• Hepatobiliary—normal hepatic function 
usually; severe degenerative VH can lead to 
hepatic dysfunction, jaundice, ascites, liver 
failure.
• All systems affected by steroid hormones or 
primary systemic disease.
• Dogs—common, often accompanies 
primary necroinflammatory liver disorders.
• Cats—rare; liver vacuolation with 
triglyceride accumulation more common (see 
Hepatic Lipidosis).SIGNALMENT
Species
Breeds predisposed to hyperadrenocorticism 
develop glycogen VH (e.g., miniature 
poodles, dachshunds, boxers, Boston terriers), 
Scottish terriers (sex hormone adrenal 
hyperplasia, hyperlipidemia), and others with 
hyperlipidemia (miniature schnauzers, 
Shetland sheepdogs) may develop mixed 
glycogen/lipid VH.
• Middle-aged to old dogs—spontaneous 
hyperadrenocorticism ( >75% older than 9 years); 
chronic systemic inflammation or neoplasia.
• Dogs of any age—iatrogenic VH subse-
quent to glucocorticoid administration.
• Young dogs or cats—genetic glycogen 
storage disease.
SIGNS
• Reflect glucocorticoids or underlying 
• Rarely, signs of hepatic disease or failure; 
hepatic failure can develop with severe 
chronic VH.
• Hepatic encephalopathy observed in some 
dogs with hepatocutaneous syndrome.
• Glucocorticoid excess—polyuria and 
polydipsia; polyphagia; endocrine alopecia; 
abdominal distention: weak muscles, loss of 
elasticity; skeletal muscle weakness; excessive 
panting; lethargy; friable skin; bruising 
tendencies; urinary tract infections, may be 
asymptomatic; corneal ulcer.
• Adrenal sex hormone hyperplasia—may 
display some signs of glucocorticoid excess 
but often fewer and less severe; endocrine 
alopecia may be only sign; some dogs remain 
asymptomatic except for chronic progressive 
marked ALP activity and degenerative VH.
• Other causes—depend on system affected; 
chronic phenobarbital may cause severe VH.
• Sex hormone hyperplasia causing VH may 
increase risk for dysplastic hepatic foci and 
hepatocellular carcinoma (e.g., Scottish 
terriers).
• Relate to steroid hormone excess or 
underlying disease; depend on severity and 
duration.
CAUSES
• Glucocorticoid administration.
• Typical hyperadrenocorticism 
(spontaneous).
• Atypical adrenal hyperplasia—overproduc-
tion of cortisol precursor sex hormones 
(spontaneous).• Systemic disease provoking acute-phase 
response or stress—e.g., severe dental disease, 
inflammatory bowel disease, chronic 
pancreatitis, systemic neoplasia (especially 
lymphoma), chronic infections (urinary tract, 
skin), hypothyroidism, many others.
• Pharmacologic doses of glucocorticoids.
• Breeds at risk for hyperadrenocorticism.
• Breeds at risk for hyperlipidemia—often 
also demonstrate combined glycogen VH: 
miniature schnauzers, Shetland sheepdogs, 
beagles.
• Dogs receiving chronic phenobarbital.
 DIAGNOSIS
• Other diffuse hepatopathies (especially 
those causing hepatomegaly and increased 
ALP activity)—passive congestion; 
neoplasia (primary or metastatic to liver); 
necroinflammatory liver disease; anticon -
vulsant hepatopathy; hepatomegaly due to 
amyloid (rare).
• VH distinguishing features—most dogs 
have increase in ALP > alanine aminotrans-
ferase (ALT) or aspartate aminotransferase 
(AST); increased cholesterol, normal serum 
bilirubin; normal/mild increase in total serum 
bile acids (TSBA); heterogeneous or 
homogeneous hyperechoic hepatic paren-
chyma on ultrasonography (nodules or “Swiss 
cheese” pattern ); characteristic cytology: 
hepatocytes engorged due to expanded 
“rarified” cytoplasm.
CBC
• Nonregenerative anemia—anemia of 
chronic disease or hypothyroidism.
• Relative polycythemia—steroid excess.
• Stress leukogram—hyperadrenocorticism; 
glucocorticoid exposure; stress of illness.
• Thrombocytosis—neoplasia; hyperadreno-
corticism; splenic disease.
• ALP markedly increased; ALP glucocorti-
coid isoenzyme cannot differentiate cause of 
VH as other liver disorders also induce this 
isoenzyme; variable 𝛾-glutamyltransferase 
(GGT), ALT, AST activity.
• Serum albumin and total bilirubin—usu-
ally normal; high bilirubin typically impli-
cates another hepatobiliary or hemolytic 
process.
• Hypercholesterolemia—hyperadrenocorti-
cism, sex hormone adrenal hyperplasia; 
breed-related hyperlipidemias; hypothyroid-
ism; pancreatitis; nephrotic syndrome.Glycogen-Type Vacuolar Hepatopathy

Canine and Feline, Seventh Edition  575
GGOTHER LABORATORY TESTS
• ALP glucocorticoid isoenzyme—see above, 
lacks specificity and thus clinical utility.
• TSBA—may be modestly increased; 
ammonia tolerance test: usually normal.
• Pituitary adrenal axis—adrenocorticotropic 
hormone (ACTH) response test or low-dose ± 
high-dose dexamethasone suppression test 
(LDDST ± HDDST) and endogenous 
ACTH may help differentiate nonadrenal 
illness, adrenal or pituitary disorders.
• Urine cortisol : creatinine ratio—at-home 
urine collection helps rule out hyperadreno-
corticism; high ratio may reflect stress or 
nonadrenal illness.
• Adrenal ultrasound imaging—nodules, 
adrenomegaly; consider dog size and age.
• If VH confirmed (liver biopsy) and 
underlying cause not evident, patient 
asymptomatic or symptomatic for adrenal 
disease—assess cortisol and sex hormone 
panel with ACTH response test.
• Thyroid testing—rules out hypothyroidism.
• T riglycerides (fasting)—hyperlipidemia.
• Canine pancreatic lipase immunoreactiv -
ity (cPLI)—may indicate “subclinical” 
pancreatic inflammation or inflammatory 
bowel disease.
IMAGING
• Abdominal radiography—reveals hepato-
megaly or other underlying conditions.
• Thoracic radiography—may reveal 
lymphadenopathy, metastatic disease, cardiac 
or pulmonary disorders.
• Abdominal ultrasonography—discloses 
hepatomegaly, diffuse hyperechoic hepatic 
parenchyma or multifocal nodular “mot-
tling”; multifocal lesions suggest nodules 
(“Swiss cheese pattern”) formed by progressive 
hepatocellular ballooning degeneration; may 
disclose underlying primary visceral abnor-
malities (e.g., mesenteric lymphadenopathy, 
neoplasia) or adrenal disorders (size/shape): 
adrenals may be large with hyperadrenocorti-
cism, sex hormone adrenal hyperplasia, 
chronic stress, or neoplasia.
• Hepatic fine-needle aspiration cytol-
ogy—22 gauge, 2.5–3.75 cm (1–1.5 in) 
US-guided needle aspiration; target nodules 
and normal parenchyma.
• Cytology—glycogen vacuolation common 
in many primary liver disorders; used to rule 
out vacuolar change; cannot definitively 
confirm illness caused only by VH.
• Hepatic biopsy—verifies VH; excludes 
other primary hepatic disease; pursue if 
systemic disorder not discovered explaining 
high ALP and VH; use US-guided T ru-Cut® 
needle biopsy to confirm VH, but may miss 
primary hepatic disease, laparoscopy 
(recommended), or laparotomy (if visceral 
inspections and biopsies indicated).• Cytologic features—hepatocellular cytosolic 
distention: “rarefication” or granular 
appearance with increased cell fragility; 
canalicular bile casts may be observed; 
primary VH not associated with inflamma-
tory infiltrates; common association with 
extramedullary hematopoiesis (EMH) may be 
misinterpreted as suppurative inflammation.
• Tissue culture and sensitivity—if suppura-
tive inflammation suspected, submit aerobic 
and anaerobic bacterial cultures.
• Coagulation assessments—prothrombin 
time (PT), activated partial thromboplastin 
time (APTT), fibrinogen, and mucosal 
bleeding time: usually normal; bench 
assessments have low predictive value in 
predicting iatrogenic hemorrhage; buccal 
mucosal bleeding time may be more relevant.
• Gross—variable; normal to moderate 
hepatomegaly; inconsistent surface irregular-
ity; tan or pale color; confusion with cirrhosis 
if nodular severe degenerative VH.
• Microscopic—marked vacuolization and 
ballooning of hepatocytes; no consistent zonal 
distribution, foci of hepatic degeneration; focal 
aggregates of neutrophils due to EMH; severe 
degenerative VH leads to parenchymal collapse, 
forming nodules surrounded by a thin partition 
with minimal collagen deposition.
 TREATMENT
DIET
• Hyperlipidemia or pancreatitis—restrict 
dietary fat and fatty supplements.
• Obesity—gradual energy restriction; treat 
predisposing disorders.
• Depend on underlying conditions.
• Adrenal masses may be resected.
• Hypophyseal masses—resection only by 
experienced surgeons; pituitary mass lesions 
may respond to radiation therapy.
• Depend on underlying disease.
• Pituitary-dependent hyperadrenocorticism 
or adrenal hyperplasia syndrome (sex 
hormone)—usually treated medically: 
op’-DDD (mitotane or Lysodren®), trilostane, 
or ketoconazole; op’-DDD preferred for sex 
hormone adrenal hyperplasia, as trilostane 
augments sex hormone accumulation; 
l-deprenyl and melatonin ineffective.
• Manage primary inflammatory disorders 
necessitating immunosuppressive or anti-inflammatory medications—use 
polypharmacy to minimize glucocorticoid 
exposure if symptomatic or progressive VH; 
see Alternative Drug(s).
• Neoplasia—tumor resection, chemotherapy, 
or radiation, as appropriate.
• Dental disease—antibiotics and dentistry.
• Inflammatory bowel disease—hypoaller-
genic/hydrolyzed protein diets and immu-
nomodulation (avoid glucocorticoids).
• Pyelonephritis, chronic dermatitis, or other 
infectious disorders—long-term antimicrobial 
treatment based on microbial culture and 
sensitivity tests; other appropriate 
• Hypothyroidism—supplemental thyroxine.
• Avoid hepatotoxic drugs if severe VH.
• Beware of drug interactions if using 
ketoconazole for adrenal disease.
• Avoid drugs with hepatic ALP induction 
effects.
Glucocorticoids—caution in VH patients; 
use lowest effective dose regimen (e.g., 
alternate-day protocol if prednisone or 
prednisolone); special caution in hyperlipi -
demia: may worsen clinical signs of 
abdominal pain, vomiting, pancreatitis; 
increase insulin requirements in diabetes 
mellitus; may augment gallbladder 
mucocele formation; may provoke hepatic 
lipidosis in cats.
Polypharmacy protocol—may reduce 
glucocorticoid usage in management of 
immune-mediated or inflammatory disorders; 
e.g., metronidazole, azathioprine, chlorambu-
cil, cyclophosphamide, mycophenolate, or 
 FOLLOW-UP
• Hepatomegaly—abdominal palpation; 
imaging.
• Normalizing enzymes—biochemistry.
• Adrenal function—ACTH stimulation 
tests.
• Neoplasia—physical exams and imaging.
• Control of infection—repeat cultures.
• Hyperlipidemia—assess gross plasma 
lipemia; measure triglycerides and 
• Limit glucocorticoid exposure.
• Use alternate-day therapy with prednisone/
prednisolone; titrate to lowest effective dose; 
use alternative medications to control primary 
illness.(continued)  Glycogen-Type Vacuolar Hepatopathy

576  Blackwell’s Five-Minute Veterinary Consult  
GPOSSIBLE COMPLICATIONS
Numerous—related to multisystemic effects 
of glucocorticoids and associated conditions.
• Most patients are asymptomatic for VH 
despite high ALP; however, progressive 
degenerative hepatopathy leading to diffuse 
nodule formation and hepatic insufficiency 
may develop in chronic VH in dogs with high 
ALP activity.
• Laboratory and pathologic features 
reversible before degenerative parenchymal 
collapse.
• Dogs with sex hormone hyperplasia, VH, 
and dysplastic hepatocellular foci appear at 
risk for development of hepatocellular 
• Pulmonary thromboembolism and 
myopathy due to hyperadrenocorticism.
• Pancreatitis associated with hyperlipidemia.
• Gallbladder mucocele.PREGNANCY/FERTILITY/BREEDING
Reproductive failure with glucocorticoid 
excess—testicular atrophy; abnormal estrus.
SYNONYMS
• Glucocorticoid hepatopathy.
• Corticosteroid hepatopathy.
• Vacuolar change.
SEE ALSO
Disease)—Cats.
Disease)—Dogs.
• Hyperlipidemia.
• GGT = 𝛾-glutamyltransferase.
• HDDST = high-dose dexamethasone 
suppression test.• LDDST = low-dose dexamethasone 
• TSBA = total serum bile acids.
(1980–2013). J Am Vet Med Assoc 2014, 
245:797–808.
Sepesy LM, Center SA, Randolph JF , et al. 
Vacuolar hepatopathy in dogs: 336 cases 
(1993–2005). J Am Vet Med Assoc 2006: 
229:246–252.
available onlineGlycogen-Type Vacuolar Hepatopathy  (continued)

Canine and Feline, Seventh Edition  577
G BASICS
OVERVIEW
Syndrome resulting from ingestion of grapes, 
raisins, sultanas, or Zante currants ( Vitis vinifera ).
• Dogs are the only species in which toxicosis 
has been well described.
• No breed, sex, or age predisposition noted.
• Anecdotal reports of toxicosis in cats and 
ferrets exist, but data are lacking to confirm.
SIGNS
• Vomiting within 24 hours of ingestion; 
vomitus frequently contains ingested fruit.
• Diarrhea, anorexia, lethargy, and abdominal 
pain may occur; stools may contain ingested fruit.
• Within 24 hours to several days, dehydra-
tion with oliguria or anuria occurs.
• Death due to anuric renal failure or euthanasia.
• Although amounts of raisins and grapes 
reported to cause toxicosis lie in the range 
2.8–9.6 g/kg and 11–31 g/kg, respectively, a 
minimum toxic dose has not been estab-
lished. Additionally, not all exposures of dogs 
to Vitis vinifera  have resulted in clinical 
evidence of renal injury.
• Ingestion of sultanas, Zante currants, and 
other varieties of Vitis vinifera  has also been 
associated with renal injury in dogs, but 
amounts associated with toxicosis have not 
• Mechanism of toxicity and toxic principle 
are unknown. Inconsistent development of 
clinical signs resulting from ingestion of Vitis 
vinifera  may reflect idiosyncratic reactions of 
individual dogs or a toxic principle that is of 
variable presence in the fruit due to variances 
in growing conditions.
• Until further toxicity data are available, all 
exposures of dogs to Vitis vinifera  should 
merit veterinary attention.
  DIAGNOSIS
Other causes of acute renal failure—ethylene 
glycol, heavy metal toxicosis, nephrotoxic 
antibiotics (e.g., aminoglycosides), nonsteroi -
dal anti-inflammatory drug toxicosis, 
hemoglobinuria, myoglobinuria, leptospirosis, 
borreliosis, and vitamin D toxicosis.
• Hypercalcemia, hyperphosphatemia, high 
creatinine and blood urea nitrogen (BUN) 
may develop within 24–48 hours of 
ingestion. Elevated creatinine and hyperphos-
phatemia tend to develop first, followed by 
elevation of BUN, with calcium elevation tending to increase 48–72 hours after 
exposure. Differentiate from vitamin D3 
toxicosis, where calcium and phosphorus 
elevate first followed by elevations in BUN 
and creatinine as kidney injury develops. Not 
all cases develop hypercalcemia or 
• Hyperkalemia, hyperamylasemia, hyperlipa-
semia, and elevated alanine aminotransferase 
(ALT) also occasionally occur.
• Isosthenuria, hyposthenuria, proteinuria, 
hematuria, and glucosuria have been 
reported.
• Granular casts may occur in the urine.
Histopathology of kidneys reveals acute 
diffuse renal tubular degeneration and 
necrosis.
 TREATMENT
• Gastrointestinal decontamination (induc-
tion of emesis, administration of activated 
charcoal) should follow ingestion of grapes or 
raisins by dogs.
• Fluid diuresis (2–3 times maintenance) for 
minimum of 48 hours is recommended, 
longer if renal failure develops. Fluid choice 
may vary with circumstance, but 0.9% NaCl 
is most commonly recommended.
• Monitor serum chemistry values, particu-
larly renal values, for minimum of 72 hours, 
longer if renal failure develops.
• Correct fluid imbalances (e.g., dehydration).
• Monitor fluid in/out.
• Diuretics (e.g., furosemide, mannitol, 
dopamine) if oliguria or anuria develops.
• Hemodialysis or peritoneal dialysis may be 
required in anuric patients.
• Emetics—3% hydrogen peroxide 2.2 mL/
kg up to a maximum of 45 mL/dog PO; may 
repeat once if first dose unsuccessful; or 
apomorphine crushed and diluted with sterile 
saline and instilled in conjunctival sac, rinse 
eye after emesis, or 0.03 mg/kg IV.
• Activated charcoal—1–3 g/kg PO.
Management of Oliguric or Anuric Renal 
Failure
• Mannitol 0.25–0.5 g/kg of 20–25% 
solution IV over 15–20 min, repeat q4–6h or 
administer as CRI of 8–10% solution for 
12–24h.
• Furosemide 2 mg/kg IV, repeat at 4 mg/kg 
if no diuresis within 1h; use with dopamine 
for best results.
• Dopamine 0.5–3  μg/kg/min.CONTRAINDICATIONS/POSSIBLE 
N/A
 FOLLOW-UP
• In dogs developing renal insufficiency, 
monitor renal values until they return to 
normal.
• Some dogs may develop irreversible renal 
injury requiring lifelong management.
• Evidence of pancreatitis developed in 3 of 
43 dogs with acute renal injury following 
Vitis vinifera  ingestion.
https://www.aspcapro.org/animal-health-
toxicology-poison-control/
people-pet-food-dangers
Eubig PA, Brady MS, Gwaltney-Brant S, 
et al. Acute renal failure in dogs after 
ingestion of grapes or raisins: a retrospective 
evaluation of 43 dogs (1992–2002). J Vet 
Intern Med 2005;19:663–674.
Mostrom MS. Grapes and raisins. In: 
Peterson M, Talcott PA, eds., Small Animal 
Toxicology, 3rd ed. St. Louis, MO: 
Saunders, 2006, pp. 569–572.
Author  Sharon Gwaltney-Brant
Consulting Editor  Lynn R. HovdaGrape and Raisin Toxicosis

578  Blackwell’s Five-Minute Veterinary Consult  
H  BASICS
OVERVIEW
• Five types—trichoepithelioma and 
trichoblastoma are most common types, but 
uncommon types include infundibular 
keratinizing acanthoma, tricholemmoma, and 
pilomatricoma; these are differentiated based 
on their origin: trichoepithelioma, trichoblas-
toma, infundibular keratinizing acanthoma, 
and tricholemmoma, which arise from 
keratinocytes in the outer root sheath of the 
hair follicle (± hair matrix); and pilomatri-
coma, which arises from the hair matrix. • All 
types—generally benign; a few published 
reports of malignant trichoepitheliomas, 
trichoblastomas, and pilomatricomas. 
• Approximately 5% of all skin tumors in 
dogs and 1% of all skin tumors in cats.
• Dog and cat. • Age—usually >5 years. • No 
sex predisposition. • T richoepithelioma—
common in dogs; rare in cats; golden 
retrievers, basset hounds, German shepherds, 
cocker spaniels, Irish setters, English springer 
spaniels, miniature schnauzers, and standard 
poodles may be predisposed; Persian and 
Siamese cats. • T richoblastoma—common in 
dogs; common in cats; poodles and cocker 
spaniels may be predisposed; no known breed 
predisposition in cats. • Infundibular 
keratinizing acanthoma—uncommon in dogs 
and cats; Norwegian elkhound, keeshond, 
and German shepherd dog may be predis -
posed; no known breed predisposition in cats. 
• T richolemmoma—uncommon in dogs 
and cats; Afghan hounds may be predisposed; 
no known breed predis  position in cats. 
• Pilomatricoma—uncommon in dogs and 
cats; Kerry blue terriers, Old English sheepdogs, 
and miniature poodles may be predisposed; no 
known breed predisposition in cats.
SIGNS
• Usually a solitary mass. • T richoepithelioma—
common on the lateral thorax and dorsal 
lumbar area (dogs) and head (cats). 
• T richoblastoma—common on the head and 
neck, especially the base of the ear (dogs) and 
cranial half of the trunk (cats). • Infundibular 
keratinizing acanthoma—common on the back, 
neck, and limbs (dogs).  • T richolemmoma—
common on the head and neck (dogs). 
• Pilomatricoma—common on the back, 
limbs, shoulders, flanks, and tail. • Firm, 
round, elevated, well-circumscribed, often 
hairless, or ulcerated dermoepithelial masses 
or nodules.
Unknown, some genetic predisposition.  DIAGNOSIS
Distinguish from other tumors, including 
basal cell tumor and squamous cell carci-
noma, and from epidermal inclusion cysts.
• Fine-needle aspiration and cytopathology. 
• Tissue biopsy and histopathology.
• Fine-needle aspiration cytology is very 
similar among all hair follicle tumors with 
basaloid and ghost cells; the exception to this 
rule is trichoblastomas, which have abundant 
pink matrix and scattered spindle cells. 
• T richoepithelioma—varies in degree of 
differentiation and site of origin (root sheath 
or hair matrix); horn cysts, lack of desmosomes, 
and differentiation toward hair follicle-like 
structures and formation of hair common. 
• T richoblastoma—four basic subtypes 
including ribbon, trabecular, granular, and 
clear cell; ribbon have basaloid cells in 
branding, winding, and radiating columns; 
trabecular have basaloid cells with prominent 
peripheral palisading; granular is identical to 
ribbon type but many of the cells are larger 
cells with granular or vacuolated cytoplasm; 
clear cell have basaloid cells in ribbon pattern 
with some cells having sebaceous differentia-
tion. • Infundibular keratinizing acan-
thoma—characterized by keratin-filled crypt 
in the dermis that opens to the skin surface. 
• T richolemmoma—characterized by nodular 
proliferation of keratinocytes, of which many 
are clear and surrounded by thickened 
basement membrane. • Pilomatricoma—
characterized by a variable proliferation of 
basophilic cells resembling hair matrix cells 
and fully keratinized, faintly eosinophilic cells 
with a central unstained nucleus (shadow 
cells); calcification common; features of 
malignancy are present with the occasional 
malignant pilomatricoma.
  TREATMENT
Complete excision, cryotherapy, or electrosur-
gery—curative with most cases.
• Isotretinoin (1 mg/kg q24h PO) was used to 
successfully control multiple pilomatricomas in one dog and multiple infundibular keratinizing 
acanthomas in some dogs. • Multimodal 
analgesia recommended for painful lesions.
N/A
  FOLLOW-UP
• Monitor for local recurrence. • Prognosis 
usually excellent; multiple reports of 
metastatic disease with the less common 
canine malignant pilomatricomas.
Abramo F , Pratesi F , Cantile C, et al. Survey 
of canine and feline follicular tumours and 
tumour-like lesions in central Italy. J Small 
Anim Pract 1999, 40:479–481.
Adedeji AO, Affolter VK, Christopher MM. 
Cytologic features of cutaneous follicular 
tumors and cysts in dogs. Vet Clin Pathol 
2017; 46(1):143–150.
Beck A, Huber D, Šćuric V, et al. A four year 
retrospective study of the prevalence of 
canine follicular tumours in Croatia. 
Veterinarski Arhiv 2016, 86(3):453–466.
Toma S, Noli C. Isotretinoin in the treatment 
of multiple benign pilomatrixomas in a 
mixed-breed dog. Vet Dermatol 2005, 
16(5):346–350.
Louis-Philippe de Lorimier.Hair Follicle Tumors

Canine and Feline, Seventh Edition  579
H BASICS
An offensive odor emanating from the oral 
cavity.
• The sour milk odor accompanying 
periodontal disease may result from bacterial 
populations associated with plaque, calculus, 
unhealthy oral cavity tissues, decomposing 
food particles retained within the oral cavity, 
and tissue necrosis.
• Contrary to common belief, neither normal 
lung air nor stomach aroma contributes.
• The most common cause is periodontal 
diseases caused by plaque bacteria.
• A bacterial biofilm forms over a freshly 
cleaned and polished tooth as soon as the 
patient starts to salivate; bacteria attach to the 
pellicle within 6–8 hours; within days, the 
plaque becomes mineralized, producing 
calculus; as plaque ages gingival inflammation 
(gingivitis) may occur and progress into 
periodontitis (tooth support loss). Eventually 
the bacterial flora changes from a predomi-
nantly nonmotile Gram-positive aerobic 
coccoid flora to a more motile, Gram-
negative anaerobic population including 
Prophyromonas , Bacteroides , Fusobacterium , 
and Actinomyces  spp.
• The rough surface of calculus attracts more 
bacteria-laden biofilm, irritating the free 
gingiva; as the inflammation continues, the 
gingival sulcus is transformed into a 
periodontal pocket, which accumulates food 
debris and bacterial breakdown products, 
generating oral malodor (halitosis).
• The primary cause of malodor is Gram-
negative anaerobic bacteria that generate 
volatile sulfur compounds (VSCs), such as 
hydrogen sulfide, methyl mercaptan, 
dimethyl sulfide, and volatile fatty acids.
• VSCs may also play a role in periodontal 
disease, affecting the integrity of the tissue 
barrier, allowing endotoxins to produce 
periodontal destruction, endotoxemia, and 
Species
Small breeds and brachycephalic breeds are 
more prone to oral disease because the teeth 
are closer together, smaller animals live 
longer, and their owners tend to feed softer 
food.
Older animals are predisposed.SIGNS
• When oral malodor is secondary to oral 
disease, ptyalism (with or without blood), 
pawing at mouth, and anorexia may occur.
• In most cases, no clinical signs are present 
other than the odor.
CAUSES
• Eating malodorous food.
• Metabolic—diabetes, uremia.
• Respiratory—rhinitis, sinusitis, neoplasia.
• Gastrointestinal—megaesophagus, 
neoplasia, foreign body.
• Dermatologic—lip-fold pyoderma.
• Dietary—fetid foodstuffs, coprophagy.
• Oral disease—periodontal disease and 
ulceration, orthodontic, pharyngitis, 
tonsillitis, neoplasia, foreign bodies.
• T rauma—electric cord injury, open 
fractures, caustic agents damaging oral 
cavity.
• Infectious—bacterial, fungal, viral 
infections of oral cavity.
• Autoimmune diseases of oral cavity.
 DIAGNOSIS
Usually normal. Might see changes consistent 
with diabetes mellitus or renal disease.
IMAGING
Intraoral radiographs are appropriate to help 
diagnose causes of halitosis.
• Hydrogen sulfide, mercaptans, and volatile 
fatty acids are the primary components of 
halitosis; an industrial sulfide monitor can be 
used to measure sulfide concentration in peak 
parts per billion.
• Additional diagnostic procedures to 
evaluate periodontal disease include intraoral 
radiography, probing pocket depths, 
attachment levels, and tooth mobility.
 TREATMENT
• Following appropriate tooth-by-tooth 
diagnostics (periodontal probing, intraoral 
imaging, mobility evaluation), under 
anesthesia all teeth should be ultrasonically 
scaled, and polished; a curette should be used 
to remove remaining plaque and calculus 
accessible subgingivally.
• Once the specific cause of halitosis is 
known, direct therapy at correcting existing 
pathology; often multiple teeth need to be 
extracted when advanced periodontal disease 
is the cause of halitosis.CLIENT EDUCATION
• Halitosis is generally a sign of an unhealthy 
oral cavity and should prompt oral assessment 
under general anesthesia, treatment, and 
prevention.
• Initiate preventive measures to ensure  
good oral health (e.g., twice-daily  
brushing or wiping teeth, recommend 
accepted Veterinary Oral Heath Council 
products).
Oral assessment performed under gen-
eral anesthesia with intraoral radiographs 
and probing treatment including  
extraction of teeth with greater than 50% 
support loss.
• Antibiotics are not indicated to treat 
halitosis.
• Controlling periodontal pathogens helps 
control dental infections and accompanying 
malodor; when accompanied by follow-up 
home care, has been shown to decrease 
pocket depth.
• Weekly application of a plaque-retardant 
gel has been shown to decrease plaque in dogs 
and cats.
• The use of oral care products that contain 
metal ions, especially zinc, inhibits odor due 
to the affinity of the metal ion to sulfur; 
zinc complexes with hydrogen sulfide to 
form insoluble zinc sulfide; zinc interferes 
with microbial proliferation and calcifica -
tion of microbial deposits (by interfering 
with the crystal development of calculus). 
Topical treatment with zinc ascorbate 
cysteine gel usually reduces halitosis within 
30 minutes.
 FOLLOW-UP
Evaluate for recurrence of signs.
• Daily brushing or friction wipes to remove 
plaque and control dental disease and odor; 
periodic veterinary examinations to monitor 
care.
• Veterinary Oral Health Council (VOHC.
org) was created to accept products that 
decrease the accumulation of plaque and/or 
tartar; additionally those products accepted 
are considered safe to use.
Varies with underlying cause.Halitosis

580  Blackwell’s Five-Minute Veterinary Consult  
H MISCELLANEOUS
SYNONYMS
• Bad breath.
• Fetor ex ore.
• Fetor oris.
• Foul breath.
• Malodor.
SEE ALSO
Periodontal Disease.
• VSC = volatile sulfur compounds. Suggested Reading
Di Cerbo A, Pezzuto F , Canello S, et al. 
Therapeutic effectiveness of a dietary 
supplement for management of halitosis in 
dogs. J Vis Exp 2015, 101:e52717. doi: 
10.3791/52717
Eubanks DL. Canine oral malodor. J Am 
Anim Hosp Assoc 2006, 42(1):77–79.
Eubanks DL. “Doggy breath”: what causes it, 
how do I evaluate it, and what can I do 
about it? J Vet Dent 2009, 26(3):192–193.
Jeusette IC, Román AM, Torre C, et al. 
24-hour evaluation of dental plaque bacteria 
and halitosis after consumption of a single 
placebo or dental treat by dogs. Am J Vet Res 2016, 77(6):613–619. doi: 10.2460/
ajvr.77.6.613
Wiggs RB, Lobprise HB. Veterinary 
Dentistry: Principles and Practice. 
Philadelphia, PA: Lippincott-Raven, 1997.
available onlineHalitosis  (continued)

Canine and Feline, Seventh Edition  581
H BASICS
Compulsive pressing of the head against a 
wall or other object for no apparent reason.
• Alterations in behavior—caused by lesions 
in the prosencephalon (i.e., cerebrum, limbic 
system, thalamus, and hypothalamus), 
particularly those affecting the limbic system 
and frontal and temporal cortices.
• Lesions may result in compulsive pacing; 
when an obstacle (e.g., a wall) is reached, the 
animal may press its head against it for long 
periods of time, apparently unable to turn 
and move away.
• Apparent inability to voluntarily move 
away—may reflect impaired integration of 
sensory information, leading to inappropriate 
behavior.
Nervous
GENETICS
N/A
N/A
Dogs and cats of any age, breed, and sex.
SIGNS
• Head pressing—just one sign of prosen-
cephalon disease.
• Compulsive pacing and circling toward the 
side of the lesion; circling can be toward 
either side if lesion is centrally located.
• Change in learned behavior, including loss 
of sleep cycles.
• Contralateral postural reaction deficits.
• Contralateral visual deficits with normal 
pupillary light reflexes.
• Contralateral facial hypalgesia.
• Anatomic—hydrocephalus, most com-
monly in young toy-breed dogs; lissencephaly 
(Lhasa apsos).
• Metabolic—hepatic encephalopathy as a 
result of a portosystemic shunt or severe 
hepatic disease; severe hyper- or hyponatremia.
• Nutritional—very unusual since most pets 
are fed compounded diets; thiamine 
deficiency can occur in cats fed a diet of raw 
fish, if thiamine supplementation in canned 
food is insufficient or in cats with severe 
malabsorptive syndromes; however, vestibular 
signs predominate.
• Neoplastic—primary (e.g., glioma, 
meningioma) or metastatic (e.g., hemangio-
sarcoma) tumors affecting the brain; more 
common in older animals ( >6 years).• Immune-mediated/inflammatory—granu-
lomatous meningoencephalitis; necrotizing 
encephalitides (Maltese encephalitis, pug 
encephalitis); meningoencephalitis of 
unknown etiology.
• Infectious (dogs)—viral (rabies virus, 
canine distemper virus), rickettsial ( Ehrlichia 
canis, Rocky Mountain spotted fever), 
caninum ), or fungal ( Blastomyces , 
Cryptococcus ); rabies is of particular impor-
tance because neurons in the limbic system 
are frequently infected in carnivores.
• Infectious (cats)—viral (rabies, feline 
infectious peritonitis, feline leukemia virus: 
associated immunosuppression predisposes to 
other encephalitides and neoplasia; feline 
immunodeficiency virus: can cause encepha-
lopathy primarily and can predispose to other 
encephalitides and neoplasia due to immuno-
suppression); Bartonella henselae ; Cuterebra  
migration; toxoplasmosis; Cryptococcus  and 
other fungal infections.
• Toxic—e.g., lead poisoning.
• T rauma.
• Vascular—intracranial hemorrhage as a 
result of hypertension (consider in older cats 
with hyperthyroidism, diabetes, or chronic 
renal insufficiency); bleeding disorder (either 
primary or secondary to rodenticide toxicity); 
ischemia (feline ischemic encephalopathy or 
secondary to systemic metabolic, inflamma-
tory, or neoplastic disease).
 DIAGNOSIS
A newly blind animal might bump into 
objects, but rapidly recognizes its environ-
ment and acts visual; an animal with a 
prosencephalic lesion continues bumping into 
objects despite normal ocular exam.
• May reflect a metabolic or toxic cause.
• Hepatic encephalopathy—decreased serum 
albumin, blood urea nitrogen, cholesterol, 
and glucose concentrations, with or without 
elevated alanine phosphatase (ALP), alanine 
aminotransferase (ALT), and bilirubin 
concentrations; microcytic anemia may be 
present; ammonium biurate crystals may be 
present in the urine.
• Lead toxicity—basophilic stippling of 
erythrocytes; presence of reticulocytes and 
nucleated red blood cells (RBCs) in the 
absence of anemia.
• Encephalitis—findings often unremarkable, 
but may reflect an inflammatory process (e.g., 
with fungal infection).
• CNS lymphoma—may see evidence of 
bone marrow involvement.OTHER LABORATORY TESTS
• Bile acid tolerance—to diagnose hepatic 
encephalopathy; blood ammonia concentra-
tions may also be elevated.
• Acute and convalescent serologic titers—
to diagnose rickettsial, protozoal, fungal, 
and viral diseases; for some infections (e.g., 
canine distemper virus, Toxoplasma , 
Cryptococcus ) also measure cerebrospinal 
fluid (CSF) antibody or antigen 
(Cryptococcus ) titers.
• PCR on CSF and serum—to diagnose 
rickettsial, bacterial, protozoal, fungal, and 
viral diseases; sensitive and specific if the 
infectious agent is present in CSF or serum.
• Blood lead concentration—to diagnose lead 
toxicity.
IMAGING
• Thoracic radiography—recommended 
for older patients to identify metastatic 
disease.
• Abdominal ultrasonography— recom-
mended for older patients if intra-abdominal 
neoplasia is suspected; indicated if a porto -
systemic shunt or other hepatic disease is 
• Rectal scintigraphy—may be used to 
definitively diagnose a portosystemic shunt.
• Brain CT or MRI—to identify intracranial 
masses, malformations, skull fractures, 
inflammation, and hemorrhage.
• Ultrasonography of the brain via persistent 
fontanels—may be used to diagnose hydro -
cephalus in young dogs.
• Fundic examination—to identify 
 chorioretinitis (evidence of infectious/
inflammatory disease) and vascular lesions.
• Blood pressure measurement to identify 
• CSF analysis—to diagnose encephalitis.
Findings at necropsy will reflect the 
etiology.
 TREATMENT
• Severe clinical signs—hospitalization for 
diagnostic workup and treatment.
• Suspected rabies—quarantine outdoor 
animal with no vaccination or unknown 
vaccination history when rapidly progressive 
neurologic signs are present and animal lives 
in a rabies-endemic area; minimize the 
number of people in contact with the animal, 
and maintain a contact log; if neurologic 
signs deteriorate rapidly, euthanize the animal 
and send it to a public health laboratory to be 
tested for rabies.Head Pressing

582  Blackwell’s Five-Minute Veterinary Consult  
HNURSING CARE
• When hospitalized, patients should be 
monitored closely for deterioration in mental 
status and for seizures.
• Maintenance IV fluids may be necessary for 
patients with severe prosencephalic syndrome.
• The cage may need to be padded to avoid 
self-trauma if constantly head pressing and 
pacing.
• Eyes should be monitored regularly for 
development of corneal ulcers due to 
self-induced trauma.
• Central IV catheters should be placed in the 
saphenous vein rather than the jugular vein if 
possible, to avoid increasing intracranial 
pressure by occlusion of the jugular veins.
ACTIVITY
N/A
DIET
• Suspected hepatic encephalopathy—appro-
priate low-protein diet.
• Hand-feeding may be necessary in severely 
encephalopathic patients; risk of aspiration if the 
patient fails to prehend and swallow correctly.
• Specific to the underlying condition.
• Clients should be warned about the 
possibility of seizures, be provided with a 
description of a seizure, and given instruc-
tions on what to do if a seizure occurs.
• Clients should be provided with a 
description of signs of acute decompensation 
due to brain herniation.
• If signs are due to intracranial disease, 
elevated intracranial pressure is likely and 
therefore there is a risk of herniation during 
anesthesia, with induction and recovery from 
anesthesia posing the highest risk; patients 
should be ventilated carefully to ensure that 
their partial pressure of carbon dioxide 
(pCO2) remains within normal limits 
(35–45 mmHg).
• Hydrocephalus can be treated by placement 
of a ventriculo-peritoneal shunt.• Brain neoplasia, in particular extra-axial 
tumors such as meningiomas, can be treated 
surgically if tumor location accessible.
• Different causes require different treatment; 
do not initiate therapy until a diagnosis has 
been established.
• If patient’s mental status deteriorates 
suggesting impending brain herniation, 
mannitol (0.25–1 g/kg IV over 10–30 min) 
or hypertonic saline (4 mL/kg of 7.5% or 
5.3 mL/kg of 3%) can be used to transiently 
reduce intracranial pressure; treatment can be 
repeated, but recurrent use will simply result 
in dehydration.
• Furosemide (0.7 mg/kg IV) given prior to 
administration of mannitol can complement 
the use of mannitol and prolong its effect.
N/A
Sedatives should be used with caution in 
patients exhibiting head pressing, because 
they prevent assessment of mental status 
changes and might suppress respiratory 
drive, causing an increase in pCO2 and 
thus causing an increase in intracranial 
pressure.
N/A
 FOLLOW-UP
• Periodic repeat neurologic examinations to 
monitor progress.
• See specific diseases.
N/A
N/A
N/A
• Rabies should be considered in endemic 
areas.
• Fungal infections may be zoonotic if spores 
are released; most likely to occur if exudative 
skin lesions are present.
SEE ALSO
• Brain Injury.
• Hydrocephalus.
• ALP = alanine phosphatase.
• pCO2 = partial pressure of carbon dioxide.
http://www.ivis.org/advances/Vite/braund1/
chapter_frm.asp?LA=1#Cerebral_Syndrome
Bagley RS, Platt SR. Coma, stupor and 
mentation changes. In: Platt SR, Olby NJ, 
eds. BSAVA Manual of Canine and Feline 
Neurology, 4th ed. Gloucester: BSAVA, 
2013, pp. 136–166.
Dewey CW. Encephalopathies: disorders of 
the brain. In: Dewey CW. ed. A Practical 
ed. Ames, IA: Wiley-Blackwell, 2008, pp. 
115–220.
Author  Natasha J. OlbyHead Pressing  (continued)

Canine and Feline, Seventh Edition  583
HHead Tilt
  BASICS
Tilting of the head away from its normal 
orientation with the trunk and limbs; usually 
associated with disorders of the vestibular 
system.
• Vestibular system—coordinates position 
and movement of the head with that of the 
eyes, trunk, and limbs by detecting linear 
acceleration and rotational movements of the 
head; includes vestibular nuclei in the rostral 
medulla of the brainstem, vestibular portion 
of the vestibulocochlear nerve (cranial nerve 
[CN] VIII), and receptors in the semicircular 
canals of the inner ear.
• Head tilt—most consistent sign of diseases 
affecting the vestibular system and its 
projections to the cerebellum, spinal cord, 
cerebral cortex, reticular formation, and 
extraocular muscles (via medial longitudinal 
fasciculus); usually ipsilateral to the lesion.
Nervous—peripheral or CNS.
SIGNS
• Ensure that abnormal head posture is true 
head tilt and not a head turn; i.e., turning of 
the head and neck to the side as if to turn in a 
circle.
• Head tilt may not be present if disease is 
CAUSES
Peripheral Disease
• Anatomic—congenital head tilt.
• Metabolic—hypothyroidism; pituitary 
chromophobe adenoma; paraneoplastic 
disease.
• Neoplastic—nerve sheath tumor of CN 
VIII; neoplasia of the bone and surrounding 
tissue (e.g., osteosarcoma, fibrosarcoma, 
chondrosarcoma, and squamous cell 
carcinoma).
• Inflammatory—otitis media and interna; 
primarily bacterial but also parasitic (e.g., 
Otodectes ), and fungal; foreign body; 
nasopharyngeal polyp(s).
• Idiopathic—canine geriatric vestibular 
disease; feline idiopathic vestibular disease.
• Immune-mediated—cranial nerve 
• Toxic—aminoglycosides, lead, 
hexachlorophene.
• T raumatic—fracture of tympanic bulla or 
petrosal bone; ear flush.
Central Disease
• Degenerative—storage disease; 
demyelinating disease; vascular event.
• Anatomic—hydrocephalus.
• Neoplastic—glioma, choroid plexus 
papilloma, meningioma, lymphoma, nerve sheath tumor, medulloblastoma, skull tumor 
(e.g., osteosarcoma); metastasis (e.g., 
hemangiosarcoma, melanoma).
• Nutritional—thiamin deficiency.
• Inflammatory, infectious—viral (e.g., feline 
infectious peritonitis [FIP], canine distemper); 
protozoal (e.g., toxoplasmosis, neosporosis); 
fungal (e.g., cryptococcosis, blastomycosis, 
histoplasmosis, coccidioidomycosis, nocardiosis); 
bacterial (e.g., extension from otitis media 
and interna); parasitic (e.g., Cuterebra  
larvae); rickettsial (e.g., ehrlichiosis); algae 
(protothecosis).
• Inflammatory, noninfectious—
granulomatous meningoencephalomyelitis 
(GME), meningoencephalitis of unknown 
etiology/origin (MUE/MUO), breed-specific 
meningoencephalitis (e.g., necrotizing 
encephalitis).
• T rauma—fracture petrosal bone with 
brainstem injury.
• Administration of ototoxic drugs.
• Metronidazole treatment.
• Thiamin-deficient diet.
• Otitis externa, media, and interna.
  DIAGNOSIS
Vestibular Disease
• Unilateral disease—head tilt usually toward 
side of lesion; usually accompanied by other 
vestibular signs, e.g., abnormal nystagmus 
(resting, positional) with fast phase usually in 
the direction opposite the tilt; ventral 
deviation of the eye (vestibular strabismus) 
ipsilateral to the tilt observed with elevation 
of the head; ataxia and disequilibrium with 
tendency to fall, lean, and/or circle toward 
the side of the tilt.
• Bilateral disease—head tilt may be absent 
or mild on the more severely affected side; 
abnormal nystagmus may be present; 
physiologic nystagmus (i.e., normal vestibular 
nystagmus) may be depressed or absent; may 
have wide side-to-side swaying movements of 
the head (especially evident in cats); may have 
wide-based stance or crouched posture with 
reluctance to move.
• Head tilt—localizes either to peripheral  
(e.g., vestibular portion of CN VIII or 
receptors in the inner ear) or central  (e.g., 
vestibular nuclei and their neuronal 
pathways) nervous system.
• Peripheral deficits—horizontal or rotatory 
nystagmus with fast phase opposite the head 
tilt; possible concomitant ipsilateral facial 
nerve paresis or paralysis and/or Horner’s 
syndrome, and/or decreased tear production 
because of the close association of CN VIII with CN VII and the sympathetic nervous 
system in the petrosal bone and tympanic 
bulla.
• Central deficits—vertical, horizontal, or 
rotatory nystagmus that can change direction 
with position of the head; altered mentation; 
ipsilateral paresis and/or proprioceptive 
deficits; central signs related to cerebellum, 
rostral medulla, and pons; in some patients, 
multiple CN involvement.
• Paradoxical vestibular syndrome—with 
lesions in the caudal cerebellar peduncles, or 
flocculonodular lobes of cerebellum; 
vestibular signs (e.g., head tilt, nystagmus) 
contralateral to the lesion, whereas the 
cerebellar signs and proprioceptive deficits are 
ipsilateral to the lesion.
Nonvestibular Head Tilt and Head 
Posture
• Uncommon.
• Unilateral midbrain lesions can cause severe 
rotation of the head ( >90°) toward the side 
opposite the lesion; no other vestibular signs; 
tilt corrects when patient is blindfolded.
• Adversive syndrome—observed with rostral 
thalamic or frontoparietal lobe lesions; head 
turn, neck curvature, and/or compulsive 
circling can be misinterpreted as vestibular 
deficits; may have postural reaction, menace, 
and/or sensory deficits that are contralateral 
to the lesion; compulsive turning is usually in 
large circles and is without the disequilibrium 
and true head tilt of vestibular disease.
• Mild anemia—hypothyroidism.
• Leukocytosis with neutrophilia—otitis 
media and interna.
• Thrombocytopenia—ehrlichiosis.
• Hypercholesterolemia—hypothyroidism.
• High serum globulin concentration—FIP .
• T4, free T4, free T4 by equilibrium dialysis 
(FT4 EQD), and endogenous thyroid-
stimulating hormone (TSH) levels—if 
hypothyroidism is suspected based on 
physical examination and associated unilateral 
or bilateral involvement of CN VIII and 
possibly VII.
• Bacterial culture and sensitivity—sample 
from myringotomy or surgical drainage of 
tympanic bulla if otitis media/interna is 
• Microscopic examination of ear swab—
parasites (e.g., Otodectes ).
• Serologic testing—infectious causes (e.g., 
canine distemper; FIP; protozoal, fungal, 
rickettsial diseases).
IMAGING
• Radiographs of tympanic bullae and 
skull—normal radiographs do not rule out 
bulla disease.
• CT and MRI—valuable to confirm bulla 
lesions, CNS extension from peripheral

584  Blackwell’s Five-Minute Veterinary Consult  
Hdisease, localize tumor, granuloma, and 
document extent of inflammation.
• Cerebrospinal fluid (CSF)—from cerebello-
medullary cistern; for evaluating central 
vestibular disease; detects inflammatory 
process; protein electrophoresis and titers to 
match with serologic testing if indicated; 
collection may put the patient at risk for 
herniation if elevated intracranial pressure.
• Brainstem auditory-evoked response 
(BAER)—assess cochlear portion of CN VIII 
and brainstem auditory pathways; particularly 
valuable for evaluating peripheral vestibular 
disease, because some diseases may cause 
ipsilateral deafness (e.g., otitis media/interna), 
whereas other diseases (e.g., canine geriatric 
and feline idiopathic vestibular diseases) affect 
only the vestibular portion of CN VIII.
• Biopsy—bone, tissue in tympanic bulla 
when a tumor, polyp, or osteomyelitis is 
suspected; brainstem mass (e.g., cerebello-
medullary angle) difficult to approach and 
remove surgically.
  TREATMENT
• Inpatient versus outpatient—depends on 
severity of signs (especially vestibular ataxia), 
size and age of patient, and need for 
supportive care.
• Supportive fluids—replacement or 
maintenance IV fluids may be required in 
acute phase when disorientation, nausea, and 
vomiting preclude oral intake; especially 
important in geriatric patients; maropitant—
dog: 1 mg/kg SC q24h for up to 5 days or 
2 mg/kg PO q24h for up to 5 days; cat: 
1 mg/kg SC/PO for up to 5 days to help 
manage nausea (questionable benefit).
• Diet—as usual unless there is thiamin 
deficiency (e.g., exclusively fish diet without 
vitamin supplementation); restrict oral intake 
if nausea and vomiting; caution: aspiration 
secondary to abnormal body posture in 
patients with severe head tilt and 
disequilibrium or brainstem dysfunction.
• Discontinue drug if toxicity suspected.
• Sedative for severe disorientation and 
ataxia—e.g., dog: acepromazine 0.02–
0.05 mg/kg IV/IM/SC to max 2 mg; 
dexmedetomidine 1–2  μg/kg IV; diazepam 
2–10 mg/dog PO/IV q8h.
• Surgical treatment—to drain bulla with 
otitis media, remove nasopharyngeal polyp in 
cats, and resect tumor, if accessible.
• Otitis media and interna—broad-spectrum 
antibiotic (parenteral or oral) that penetrates bone while awaiting culture results; 
trimethoprim-sulfa (15 mg/kg PO q12h or 
30 mg/kg PO q12–24h); first-generation 
cephalosporins, such as cephalexin (10–
30 mg/kg PO q6–8h) or amoxicillin–
clavulanic acid (Clavamox®—dogs: 12.5 mg/
kg PO q12h; cats: 62.5 mg/cat PO q12h; 
Clavaseptin® 12.5 mg/kg PO q12h); 
treatment for 4–6 weeks.
• Hypothyroidism—T4 replacement (dogs: 
levothyroxine 22  μg/kg PO q12h) should be 
introduced gradually in geriatric patients, 
especially with cardiac disease; response 
varies, partly depending on duration of signs 
(i.e., in some patients neuropathy is not 
reversible).
• Infectious CNS—specific treatment, if 
indicated; for bacterial diseases, antibiotic 
that penetrates the blood–brain barrier (e.g., 
trimethoprim-sulfa 15 mg/kg PO q12h; 
metronidazole 15 mg/kg q12h or 10 mg/kg 
q8h PO or slowly IV; third-generation 
cephalosporin, e.g., cefotaxime 25–50 mg/
kg IV q8h); for protozoal diseases, 
clindamycin (12.5–25 mg/kg PO q12h); for 
fungal diseases, itraconazole (dogs: 2.5 mg/
kg PO q12h or 5 mg/kg PO q24h; cats: 
5 mg/kg PO q12h), fluconazole (dogs: 
5–8 mg/kg PO q12h, 10–12 mg/kg PO 
q24h; cats: 50 mg/cat PO q12–24h); 
prognosis usually poor for protozoal, fungal, 
and viral diseases (e.g., FIP).
• GME/MUE/MUO—usually initially treated 
with steroids: dexamethasone (0.25 mg/kg PO, 
IM q12h for 3 days; followed by or starting 
with prednisone 2 mg/kg PO q24h for a 
minimum of 2 weeks; then decrease slowly); 
depending on progress, may need stronger 
immunosuppression, e.g., cytosine arabinoside 
50 mg/m2 q12h for four treatments repeated 
every 3 weeks (need to monitor CBC) or 
preferably starting with CRI of cytosine 
arabinoside at 200 mg/m2 administered IV 
over 4h, then follow every 3 weeks with SC 
injections; also consider cyclosporine and/or 
leflunomide or radiation therapy.
• T rauma—supportive care (e.g., anti-
inflammatory drugs, antibiotics, IV fluid 
administration); specific fracture repair or 
hematoma removal is potentially difficult 
considering the location.
• Canine geriatric and feline idiopathic 
vestibular disease—supportive care; 
maropitant—dog: 1 mg/kg SC q24h for up 
to 5 days or 2 mg/kg PO q24h for up to 5 
days; cat: 1 mg/kg SC/PO for up to 5 days to 
help manage nausea (questionable benefit).
• Cranial nerve polyneuropathy—response to 
prednisone good if the patient has a primary 
immune disorder.
• Thiamin deficiency—diet modification and 
thiamin supplementation.
• T rimethoprim-sulfa administration—
keratoconjunctivitis sicca (dry eye).• Avoid administering drugs into external ear 
canal (especially oil-based) if tympanic 
membrane is ruptured.
  FOLLOW-UP
• Repeat the neurologic examination as 
dictated by underlying cause.
• Head tilt may persist.
• Hypothyroidism—measure T4 
concentration 4–6 hours after treatment 3–4 
weeks after initiation of thyroid therapy or 
dosing change.
• Repeat CSF and brain imaging—with some 
central vestibular disorders.
• Monitor tear production (Schirmer tear 
test) with trimethoprim-sulfa administration.
• Prognosis for central vestibular disorders 
usually poorer than peripheral vestibular 
• Prognosis for canine geriatric and feline 
idiopathic vestibular syndromes is excellent.
• Facial nerve paresis or paralysis.
• Horner’s syndrome.
SEE ALSO
• BAER = brainstem auditory-evoked 
response.
• FT4 EQD = free T4 by equilibrium dialysis.
• GME = granulomatous 
meningoencephalomyelitis.
• MUE/MUO = meningoencephalitis of 
unknown etiology/origin.
Garosi L. Head tilt and nystagmus. In: Platt 
S, Garosi L, eds. Small Animal Neurological 
Emergencies. London: Manson, 2012, pp. 
253–263.
Rossmeisl JH. Vestibular disease in dogs and 
2010, 40:81–100.
Author  Susan M. Cochrane
available onlineHead Tilt  (continued)

Canine and Feline, Seventh Edition  585
H BASICS
OVERVIEW
• Common, very specific, benign, often 
self-limiting, head and neck tremors in dogs.
• Synonyms—head bobbing, wobbling, 
nodding, shaking, tremors; episodic head 
tremor syndrome; bobble head doll syndrome.
• A movement disorder (paroxysmal 
dyskinesia) was suspected, but the patho-
physiology remains unknown and a recent 
electroencephalographic (EEG) study may 
support an epileptic syndrome.
• All dog breeds can be affected.
• English bulldog (EB), French bulldog, 
boxer, Doberman pinscher (DP), and 
Labrador retriever are predisposed.
• Reported prevalence of 19–38% in EB.
• Reports that males are overrepresented in 
DP and EB.
• Generally starts early in life ( <3 years old), 
but can start at any age.
SIGNS
• Acute onset of head tremor episodes.
• Possible recent stressful event (heat, whelping 
with lactation, vaccination, illness, etc.).
• Littermates may be affected (familial form 
identified in DP ≤1 year old).
• None if not currently experiencing an episode.
• Typical vertical or horizontal rapid (4–8 Hertz 
or movements per second) head tremors—  
episodes last from a few seconds to a few hours.
• Variable tremor episode frequency, 
duration, and interepisode interval.
• Occasional reports of abnormal dystonic 
posture (subtle head tilt, stiffness, floppiness) 
during episodes, but not between episodes.
• Occasional reports of abnormal behavior 
(disorientation, sleepiness, agitation) 
immediately prior to episode.
• All dogs are reported to be responsive to 
their surroundings during the episode.
• Rare reports of associated generalized seizure.
• Episodes can often be interrupted by 
distraction or treats.
• Other neurologic abnormalities (ataxia, 
proprioceptive deficits, paresis) consistent 
with concurrent, unrelated neurologic disease 
(cervical spondylomyelopathy in DP , 
hemivertebrae in bulldogs) are often noted.
• Unknown pathophysiology.
• Anatomic, neoplastic, and traumatic causes 
have been ruled out by different studies.
• Genetic basis suspected but unproven.
• May be triggered by a recent stressful event.   DIAGNOSIS
• T remorgenic toxin (mycotoxin, perme-
thrins, etc.).
• Corticosteroid responsive shaker/tremor 
syndrome.
• Hypomyelinating/dysmyelinating congeni-
tal or degenerative disease.
• Cerebellar disease (intention tremor).
• Hypocalcemia.
• Hypoadrenocorticism (electrolyte imbalance).
• Epilepsy (focal or generalized seizures) or 
reactive seizures.
• Stress.
• Muscle fatigue following exercise or associated 
with generalized weakness from myopathy, 
neuropathy, or neuromuscular disease.
• History, signalment, and viewing of a video 
helps greatly in identifying this typical head 
movement and differentiating it from other 
types of tremor.
• Variation from the above-described typical 
pattern should be video-filmed and reviewed.
IMAGING
MRI might be considered if abnormalities 
other than typical head tremor noted.
Cerebrospinal fluid analysis and electrodiag-
nostic testing might be considered if 
abnormalities other than typical head 
bobbing episodes noted. Video-EEG may 
show seizure activity during an episode, but 
has been normal between episodes in one 
multicentric case series study.
Have not been studied.
  TREATMENT
• No known effective treatment.
• Interrupting the episodes by distracting the 
dog should be tried by the client.
• If head bobbing episodes significantly 
impair crucial life functions such as eating or 
sleeping, consult a veterinary neurologist for 
further recommendations.
No known effective medication.CONTRAINDICATIONS/POSSIBLE 
Commonly used antiepileptic drugs (pheno -
barbital, potassium bromide) have multiple 
significant side effects and have not been 
proven successful at treating head bobbing. 
Their use is not warranted with this condition.
  FOLLOW-UP
N/A
• Self-limiting in 49% of EB in one study.
• Benign head tremor episodes may continue 
lifelong at a variable frequency, usually 
decreasing over time.
• Prognosis is excellent as head bobbing is 
not associated with a life-threatening 
Concurrent epilepsy may be present.
There is potential genetic transmission.
• DP = Doberman pinschers.
• EB = English bulldog.
• EEG = Electroencephalography.
Guevar J, De Decker S, Van Ham LML, 
Fisher A, Volk HA. Idiopathic head tremor 
in English Bulldogs. Mov Disord 2014, 
29(2):191–194.
Wolf M, Bruehschwein A, Sauter-Louis C, 
Sewell AC, Fisher A. An inherited Episodic 
Head tremor Syndrome in Doberman 
Pinscher Dogs. Mov Disord 2011, 
26(13):2381–2386.
Author  Stéphanie Dugas
available onlineHead Tremors (Bobbing), Idiopathic—Dogs

586  Blackwell’s Five-Minute Veterinary Consult  
HHeartworm Disease—Cats
  BASICS
OVERVIEW
• Disease caused by infection with Dirofilaria 
immitis . • Microfilaremia uncommon ( <20%) 
and usually transient if present. • Prevalence 
one-tenth that of unprotected dogs. • Low 
average worm burden. • Worms are physically 
smaller but recent evidence suggests lifespan 
is similar to that in the dog.
• No age or breed predisposition. • Males 
more commonly infected naturally and easier 
to infect experimentally.
SIGNS
• Coughing (this sign is relatively uncommon 
with heart failure). • Cough will commonly 
occur early in disease prior to established 
adult infection. • Heartworm-associated 
respiratory disease (HARD)—clinical signs 
and pulmonary pathology that occur 2–4 
months post infection even when adult 
infection is never established. • Dyspnea. 
• Vomiting (undetermined cause). 
• Pulmonary thromboembolism (PTE) 
frequently results in acute respiratory failure 
and death. • Vomiting and respiratory signs 
predominate in chronic disease.
• Usually normal. • Increased bronchovesicular 
sounds. • Arrhythmia, murmur, or gallop 
rhythm should increase suspicion of primary 
cardiac disease.
• Outdoor cats at increased risk (2 : 1). 
• Feline leukemia virus (FeLV) infection not 
predisposing factor.
  DIAGNOSIS
• Asthma. • Cardiomyopathy. • Chylothorax. 
• Aelurostrongylus abstrusus  infection. 
• Paragonimus kellicotti  infection.
• Varies with stage of disease. • Mild 
nonregenerative anemia. • Eosinophilia 
inconsistent. • Concurrent basophilia should 
increase suspicion. • Hyperglobulinemia.
Microfilaria Concentration Tests
Very low sensitivity, high specificity.
Heartworm Antigen Tests
• ELISA or immunochromatographic tests. 
• Tests that detect circulating adult 
heartworm antigen (HWAg) more specific 
than antibody tests. • Positive antigen test result is strong evidence of adult heartworm 
infection. • Low worm burdens (fewer than 
five worms) and single-sex infections 
commonly result in false-negative antigen 
tests. • Data suggest heat treatment of samples 
prior to testing may significantly increase test 
sensitivity; negative result does not rule out 
heartworm disease: more than 40% of cats 
with adult infection are antigen-negative; 
many cats are symptomatic (HARD) well 
before antigen test would become positive.
Heartworm Antibody Tests
• Tests that detect circulating antibodies to 
immature and adult heartworm antigen are most 
sensitive tests for feline heartworm disease. 
• Positive result does not confirm adult infection; 
usually becomes positive within 4 months of 
infection. • The more intense the antibody 
response, the more likely adult infection. • May 
become negative in adult infections perhaps 
associated with Ag;Ab complexing.
IMAGING
• Enlarged (pulmonary artery, >1.6 times width 
of ninth rib). • Blunted, tortuous pulmonary 
arteries. • Patchy perivascular pulmonary 
infiltrates. • Pleural effusion may be present. 
• Chylothorax has been documented with 
spontaneously occurring and experimentally 
induced heartworm infections in cats.
• Dilated main pulmonary artery. 
• Identification of worms in heart or main 
pulmonary artery; most commonly seen in right 
pulmonary artery but also in right ventricle and 
atrium (hyperechoic “=” sign). • Sensitive test in 
hands of experienced echocardiographer. 
• Excludes or confirms other primary cardiac 
diseases (cardiomyopathy).
  TREATMENT
• Currently no approved or recommended 
medical adulticide therapy. • Surgical or 
catheter-based extraction may be most 
reasonable option. • Symptomatic cats should 
be stabilized (see below) prior to consideration 
of worm extraction. • Spontaneous “cure” 
probably more common in cats than dogs.
• Supplemental oxygen. • Theophylline 
(sustained-release formulation) 15–25 mg/kg 
PO q24h in evening. • Prednisolone 1–2 mg/
kg PO q12–24h for 10–14 days; then gradually 
taper and discontinue. • Doxycycline therapy 10 mg/kg PO q24h for 30 days (to eliminate 
endosymbiont Wolbachia ) may hasten worm 
death and reduce severity of pulmonary 
inflammation secondary to worm embolization. 
• Cautious balanced fluid therapy if indicated. 
• Medical adulticide therapy not currently 
recommended. • Supportive care for PTE the 
same as initial stabilization (see above).
• Aspirin therapy—no documented benefit. 
• Current information does not support use 
of melarsomine (Immiticide®) in cats.
  FOLLOW-UP
Serial evaluation of clinical response, thoracic 
radiographs, and heartworm antigen and 
antibody tests is most informative.
• Ivermectin 24  μg/kg PO q30 days. 
• Milbemycin oxime 0.5 mg/kg PO q30 
days. • Selamectin 6.6–12 mg/kg cutaneously 
q30 days. • Moxidectin 1–2 mg/kg 
cutaneously q30 days. • Administration of 
these drugs in cats is not precluded by 
antibody or antigen seropositivity.
• HARD = heartworm-associated respiratory 
disease.
• HWAg = adult heartworm antigen.
https://www.heartwormsociety.org/veterinary-
resources/american-heartworm-society- 
guidelines
Little SE, Raymond MR, Thomas JE, et al. 
Heat treatment prior to testing allows 
detection of antigen of Dirofilaria immitis  
in feline serum. Parasit Vectors 2014, 7:1.
Thomason JD, Calvert CA. Heartworm 
disease. In: Smith FWK, Tilley LP , Oyama 
MO: Saunders Elsevier, 2016.
Matthew W. Miller

Canine and Feline, Seventh Edition  587
HHeartworm Disease—Dogs
  BASICS
Disease caused by infestation with Dirofilaria 
immitis .
• Severity directly related to worm number, 
duration of infestation, host response, and 
host activity level. • Endothelial damage leads 
to myointimal proliferation and inflammation 
predisposing to periarterial edema. • Lobar 
arterial enlargement, tortuosity, and 
obstruction cause impaired compliance, loss 
of collateral recruitment, pulmonary 
hypertension (PH), right-sided congestive 
heart failure (rCHF), thrombosis. 
• Pulmonary damage exacerbated after death 
of adult worms and with exercise.
• Respiratory—PH, thromboembolism, 
allergic pneumonitis (some occult infections), 
eosinophilic granulomatosis (uncommon). 
• Cardiovascular—severe PH causes right 
ventricular hypertrophy and, in some dogs, 
rCHF (ascites). • Hemic/lymphatic/immune—
venous inflow to the heart can become 
obstructed by worms causing traumatic 
hemolytic anemia and cardiogenic shock 
(caval syndrome). • Renal/urologic—
immune-complex glomerulonephritis.
Virtually 100% in unprotected dogs living in 
highly endemic regions.
• Most common in tropical and subtropical 
zones; endemic in North, Central, and South 
America, southern Europe, and Australia. 
• Diagnosed in all 50 states of United States; 
common along Atlantic/Gulf coasts and 
Ohio/Mississippi river basins. • Ubiquitous 
mosquito vector in endemic areas.
• Medium-to-large breed dogs > small dogs. 
• Outdoor dogs > indoor dogs.
Infestation can occur at any age; most 
affected dogs 3–8 years old.
Males > females.
SIGNS
• Dogs often asymptomatic or exhibit 
minimal signs such as occasional coughing 
(mild infestation). • Coughing and exercise 
intolerance associated with moderate 
pulmonary damage (moderate infestation). 
• Cachexia, exercise intolerance, syncope, 
and/or abdominal distention (rCHF) in severely affected dogs. • Cardiogenic shock, 
pigmenturia, abdominal distention (rCHF) in 
• No abnormalities—dogs with mild and 
some with moderate infestation. • Labored 
breathing and/or crackles—dogs with severe 
PH or pulmonary thromboembolism (PTE). 
• Tachycardia, weight loss, exercise intolerance, 
syncope, coughing, pale or light pink mucous 
membranes, dyspnea. • Ascites, jugular vein 
distention/pulsation, hepatomegaly (rCHF). 
• Hemoptysis—occasionally. • Pale mucous 
membranes, dyspnea, weak pulses.
• Residence in endemic areas. • Outside 
habitat. • Lack of prophylaxis. 
• Environmental temperature >57 °F (14 °C).
  DIAGNOSIS
• Other causes of PH and thrombosis (e.g., 
hyperadrenocorticism, protein-losing 
nephropathy or enteropathy). • Chronic 
obstructive lung disease. • Pneumonia. 
• Allergic lung disease. • Other causes of 
ascites (e.g., dilated cardiomyopathy). 
• Other causes of hemolytic anemia (e.g., 
immune-mediated).
• Anemia—absent, mild, or moderate 
depending on chronicity, severity, thrombo -
embolic complications. • Eosinophilia and 
basophilia—vary. • Inflammatory leukogram 
and thrombocytopenia associated with 
thromboembolism. • Hyperglobulinemia—  
inconsistent finding. • Hemoglobinemia—
evident with caval syndrome and less often 
thromboembolism. • Proteinuria—common 
with severe and chronic infestation; due to 
immune-complex glomerulonephritis or 
amyloidosis. • Hemoglobinuria—caval 
syndrome or severe lysis with 
• Highly specific, sensitive serologic tests 
identify adult female D. immitis  antigen; test 7 
months after end of previous transmission 
season; false positives possible with Spirocerca  
infestation; in author’s experience, false 
negatives occur more commonly in shelter 
animals due to antigen-antibody complexes 
(antigen blocking); if infestation suspected with 
negative antigen test, consider heartworm heat 
treatment antigen ELISA testing. 
• Antigenemia absent in absence of adult 
female worms. • Weak positive test verified by 
repeat testing using different test and/or 
microfilaria testing. • Strong reaction indicates 
relative high worm burden or recent worm death and highly predictive of thromboembolic 
complications post adulticide therapy. 
• Microfilaria testing—mainly to confirm weak 
positive antigen tests, determine microfilarial 
status prior to using milbemycin preventatives, 
and identify microfilaria that may contribute to 
development of resistance when treated 
chronically with macrolide preventative.
IMAGING
• Use DV projection. • Main pulmonary  
artery segment enlargement, lobar arterial 
enlargement, tortuosity/pruning vary from 
absent to severe; right caudal artery > left caudal 
artery > cranial arteries. • Parenchymal lung 
infiltrates of variable severity—surround lobar 
arteries; may extend into most or all of one or 
multiple lung lobes with thromboembolism 
and/or PH. • Diffuse, symmetric, alveolar, 
interstitial infiltrates occur secondary to allergic 
reaction to microfilaria (allergic pneumonitis) 
in about 10% of occult infestations.
• Often unremarkable; may reflect right 
ventricular dilation and wall hypertrophy, 
tricuspid regurgitation, PH, small left heart 
due to underloading (pulmonary obstruction/
hypertension). • Parallel, linear echodensities 
produced by heartworms may be detected in 
right ventricle, right atrium, pulmonary arteries.
ECG
• Usually normal. • May reflect right 
ventricular hypertrophy in dogs with severe 
infestation. • Heart rhythm disturbances—
occasionally seen (atrial premature 
contractions and atrial fibrillation most 
common) in severe infestation.
• Large right heart. • Pulmonary arterial 
myointimal proliferation. • PTE. 
• Pulmonary hemorrhage. • Hepatomegaly 
and congestion in dogs with rCHF .
  TREATMENT
• Most dogs hospitalized during adulticide 
administration. • Eliminate microfilaria with 
monthly prophylaxis and doxycycline/
minocycline; milbemycin may cause rapid 
decrease in microfilaria numbers and should 
be used with caution in that scenario; dogs 
should be rendered microfilaria free 3-4 
months post diagnosis. • Hospitalization 
recommended for dogs experiencing 
thromboembolic complications.
ACTIVITY
Severely restrict activity for 4–6 weeks after 
adulticide administration.

588  Blackwell’s Five-Minute Veterinary Consult  
HCLIENT EDUCATION
• Good prognosis for animals with mild to 
moderate disease. • Post-adulticide 
pulmonary complications likely in patients 
with moderate to severe pulmonary artery 
pathology and those with high worm burden. 
• Reinfestation can occur without 
appropriate prophylaxis.
• T reatment of choice for caval syndrome. 
• Worm removal from right heart and 
pulmonary artery via jugular vein, by use of 
fluoroscopy and long, flexible alligator forceps 
or horsehair brush, highly effective for 
treating high worm burden when employed 
by experienced operator.
• Stabilize animals in rCHF with diuretics, 
inhibitor, pimobendan, sildenafil, cage rest, 
and moderate sodium restriction before 
adulticide treatment. • Stabilize pulmonary 
failure with oxygen supplementation, 
antithrombotics (e.g., clopidogrel and 
heparin), and/or anti-inflammatory dosages of 
corticosteroid depending on clinical and 
radiographic findings. • Doxycycline/
minocycline (5–10 mg/kg PO q12h) for 
4 weeks followed by 1 month wait period is 
used prior to adulticide therapy to kill 
Wolbachia , a Gram-negative, endo-symbiotic, 
intrafilarial bacterium associated with 
inflammation of the lungs and kidneys; the 
author practices adulticide therapy after 
4 weeks of treatment. • Adulticide—
melarsomine dihydrochloride (2.5 mg/kg IM/
dose): injections given into epaxial muscles 
using 22-gauge needles; apply pressure over 
injection site during and after needle 
withdrawal. • Graded-kill protocol 
recommended in most cases—administer 
one injection followed in 1 month by two 
injections (first injection on left or right 
epaxial muscles, followed by injection on 
opposite side 24h later). • For severe 
heartworm infestation with high worm 
burdens, administer one injection every 4–6 
weeks for a total of three injections; maintain 
strictest patient confinement practical for 4–6 
weeks; perform antigen test 6 months after 
third injection. • Allergic pneumonitis—
administer prednisone or prednisolone (2 mg/
kg PO q12–24h for several days) and then 
immediately administer melarsomine. • Rapid 
microfilaricidal therapy (e.g., milbemycin or 
high-dose ivermectin) not recommended—
eliminate microfilaria with monthly 
prophylaxis and doxycycline/minocycline; 
confirm elimination of microfilaria by testing 
3–4 months after initiating therapy.PRECAUTIONS
• Adulticide treatment—not indicated in 
patients with renal failure, hepatic failure 
(icterus), or nephrotic syndrome. • Caval 
syndrome—remove worms surgically and 
stabilize patient with conservative management 
for at least 1 month prior to adulticide therapy.
• Sodium heparin (75–100 units/kg SC q8h), 
clopidogrel (2–4 mg/kg PO q24h), or low 
molecular weight heparin (dalteparin: 100 units/
kg SC q12–24h) for 1–3 weeks before, during, 
and for 3 weeks after adulticide administration 
are controversial recommendations for most 
severe cases; therapy is combined with strict, 
extended cage confinement. • Sodium heparin 
(200–500 units/kg SC q8h) recommended for 
dogs with PTE or hemoglobinuria with goal of 
prolonging activated partial thromboplastin time 
(APTT) 1.5–2 times baseline. • Soft or slow kill 
methods using any macrocyclic lactone alone are 
not recommended.
  FOLLOW-UP
• Perform antigen test 6 months after 
adulticide treatment; some dogs with persistent, 
low-grade antigenemia may not require 
retreatment. • Weak antigenemia indicates 
most worms killed, pulmonary pathology will 
improve, and ivermectin prophylaxis will likely 
eventually kill remaining worms.
• Heartworm prophylaxis should be provided 
for all dogs at risk—author recommends 
year-round prophylaxis; otherwise begin with 
mosquito season and continue for 1 month 
following first frost. • In highly endemic areas, 
consider combination of heartworm 
prophylaxis, insect repellents, and ectopara -
siticides. • Antigen test 7 months after end of 
previous season. • Ivermectin (Heartgard®, 
Iverhart®, T ri-Heart®)—highly effective, 
monthly preventative; safe for microfilaremic 
dogs. • Milbemycin oxime (Interceptor®, 
Sentinel®, T rifexis®)—highly effective, monthly 
prophylaxis; acute reactions may occur when 
given to microfilaremic dogs. • Moxidectin 
(Advantage® Multi, ProHeart® 6)—topical 
solution administered monthly; slow-release 
injectable formulation (ProHeart® SR12) 
available in some countries. • Selamectin 
(Revolution®)—highly effective monthly 
topical preparation. • Administer to puppies as 
soon after 8 weeks of age as dictated by 
seasonal risk. • All prophylactic drugs can be 
administered safely to collies at labeled dosages. 
• For dogs infected with adult worms not 
already on prophylaxis, any of above drugs can 
be started immediately and should be started 
within 1 month of diagnosis; author 
recommends against using milbemycin in microfilaremic dogs. • All macrocyclic lactones 
combined with 1 month doxycycline/
minocycline therapy should eliminate 
microfilaria in 1–3 months. • Due to recent 
increase in number of lack of efficacy reports 
and concern of possible heartworm resistance 
to current heartworm preventatives, dogs 
should be rendered microfilaria free 3–4 
months post diagnosis.
• Post-adulticide PTE—may occur up to 
4–6 weeks after treatment; more likely in 
dogs with severe disease and those not 
properly confined. • Thrombocytopenia and 
• Melarsomine adverse effects—PTE (usually 
7–30 days post therapy); anorexia; injection 
site reaction: myositis; lethargy or depression; 
elevation of hepatic enzymes; paresis/paralysis/
altered mentation; lack of efficacy.
• Mild—usually uneventful with excellent 
prognosis. • Severe or caval syndrome—
guarded prognosis with higher risk of 
When anesthesia/surgery required, delay 
heartworm treatment until after procedure.
Wolbachia
• Delay adulticide treatment. 
• T ransplacental infestation by microfilaria 
can occur.
SEE ALSO
• Disseminated Intravascular Coagulation. 
• Pulmonary Thromboembolism.
• PTE = pulmonary thromboembolism. 
• rCHF = right-sided congestive heart failure.
www.heartwormsociety.org
of Clay A. Calvert
available onlineHeartworm Disease—Dogs  (continued)

Canine and Feline, Seventh Edition  589
H BASICS
• Hyperthermia is defined as an elevation in 
body temperature above the normal range; 
although published normal values for dogs 
and cats vary slightly, it is generally accepted 
that body temperatures >103 °F (39.4 °C) 
are abnormal. • Hyperthermia can be 
categorized into pyrogenic hyperthermia 
(pyrexia or fever) and nonpyrogenic hyper­
thermia. • Heat stroke is a form of nonpyro ­
genic hyperthermia that occurs when 
heat­dissipating mechanisms of the body 
cannot accommodate excessive heat; this can 
lead to multisystem organ dysfunction; 
temperatures of ≥106 °F (41.1 °C) without 
signs of inflammation are suggestive of 
nonpyrogenic hyperthermia. • Malignant 
hyperthermia is an uncommon familial form 
of nonpyrogenic hyperthermia that can occur 
secondary to some anesthetic agents. • Other 
causes of nonpyrogenic hyperthermia include 
excessive exercise, thyrotoxicosis, and 
hypothalamic lesions.
• The hypothalamic set point is changed with 
true fever; this is most likely mediated via the 
endogenous pyrogen interleukin ­1. 
• Nonpyrogenic hyperthermia does not 
change the hypothalamic set point. • The 
critical temperature leading to multiple organ 
dysfunction is 109 °F (42.7 °C). • The 
primary pathophysiologic processes of heat 
stroke are related to thermal damage, which 
can lead to cellular necrosis, hypoxemia, and 
protein denaturalization. • Heat stroke and 
its sequelae can lead to systemic inflammatory 
response syndrome (SIRS).
• Cardiovascular—hypovolemia, cardiac 
arrhythmias, myocardial ischemia, necrosis. 
• Gastrointestinal—mucosal ischemia and 
ulceration, bacterial translocation and 
endotoxemia. • Hemic/lymphatic/immune—
hemoconcentration, th  rombocytopenia, 
• He patobiliary—hepatocellular necrosis. 
• Musculoskeletal—rhabdomyolysis. 
• Nervous—neuronal damage, parenchymal 
hemorrhage, cerebral edema. • Renal/
urologic—acute renal failure.
May occur in any climate but more common 
in warm and/or humid environments.
Species
Dog and, uncommonly, cat.
• May occur in any breed. • Longhaired 
animals. • Brachycephalic breeds.Mean Age and Range
• All ages but often age extremes. • Young 
dogs may tend to overexert. • Old dogs with 
preexisting disease.
SIGNS
• Identifiable underlying cause—warm 
environmental conditions, locked in car or 
other confined area without adequate 
ventilation, grooming accident associated with 
drying cages, excessive exercise, restricted access 
to water. • Predisposing underlying disease—
laryngeal paralysis, brachycephalic obstructive 
disease, cardiovascular disease, neuromuscular 
disease, previous history of heat ­related disease.
• Panting. • Hypersalivation. • Hyperthermia. 
• Hyperemic mucous membranes. • Pale 
mucous membranes. • Cyanosis. 
• Tachycardia. • Cardiac dysrhythmias. 
• Shock. • Respiratory distress. 
• Hematemesis. • Hematochezia. • Melena. 
• Petechiation. • Changes in mentation. 
• Seizures. • Muscle tremors. • Ataxia. 
• Coma. • Oliguria/anuria. • Respiratory 
arrest. • Cardiopulmonary arrest.
CAUSES
• Excessive environmental heat and humidity 
(may be due to weather conditions or 
accidents such as enclosed in unventilated 
room, car, or grooming dryer cage). • Upper 
airway disease. • Exercise. • Toxicosis (some 
compounds that lead to seizures, i.e., 
strychnine and metaldehyde). • Anesthesia 
(malignant hyperthermia).
• Previous history of heat ­related disease. 
• Age extremes. • Heat intolerance due to 
poor acclimatization. • Obesity. • Poor 
cardiopulmonary conditioning. 
• Hyperthyroidism. • Underlying cardiopul­
monary disease. • Brachycephalic breeds. 
• Thick hair coat. • Dehydration.
 DIAGNOSIS
• If temperature exceeds 106 °F (41.1 °C) 
without evidence of inflammation should 
consider heat stroke. • Panting and hypersali­
vation may not be seen with true fever as 
hypothalamic set point has been raised.
• May help identify underlying disease process 
and/or sequelae to hyperthermia. • CBC 
abnormalities may include stress leukogram, 
leukopenia, anemia, nucleated red blood cells, 
thrombocytopenia, or hemoconcentration. 
• Biochemistry profile may show azotemia, 
hyperalbuminemia, elevations in serum enzymes 
(alanine aminotransferase, aspartate aminotrans ­
ferase, creatine kinase), hypernatremia, hyper­chloremia, hyperglycemia, hypoglycemia, 
hyperphosphatemia, hyperkalemia, hypoka ­
lemia, hyperbilirubinemia. • Urinalysis may 
show hypersthenuria, proteinuria, cylindruria, 
hemoglobinuria, myoglobinuria.
• Blood gas analysis may show mixed 
acid­base disorder, respiratory alkalosis, or 
metabolic acidosis. • Lactate concentrations 
may be elevated due to impaired perfusion. 
• Coagulation profile may indicate prolonged 
activated clotting time (ACT), prothrombin 
time (PT), or partial thromboplastin time 
(PTT); fibrin degradation products (FDP) or 
D­dimers may be positive; DIC may be 
present if PT and PTT are prolonged along 
with positive FDPs or D ­dimers and 
thrombocytopenia; if available measurement 
of antithrombin may be valuable. 
• Thromboelastography may document 
hyper ­ or hypocoagulability.
IMAGING
• Thoracic/abdominal radiographs and/or 
ultrasound may help identify underlying 
cardiopulmonary disease or predisposing 
factors. • CT or MRI may help identify 
hypothalamic lesion.
Continuous temperature monitoring.
 TREATMENT
• Early recognition is key. • Immediate 
correction of hyperthermia—spray with 
water or immerse in water prior to transport 
to veterinary facility; convection cooling 
with fans; evaporative cooling such as 
alcohol on foot pads, axilla, and groin. 
• Stop cooling procedures when temperature 
reaches 103 °F (39.4 °C) to avoid hypother ­
mia. • Oxygen supplementation via oxygen 
cage, mask, or nasal catheter. • Airway 
management in cases of laryngeal paralysis 
or edema. • Ventilatory support if required. 
• Fluid support with shock doses of 
crystalloids or colloids. • T reat complica ­
tions, seizures, DIC, renal injury, cerebral 
edema. • T reat underlying disease or correct 
predisposing factors.
• Patients should be hospitalized until 
temperature is stabilized. • Most patients 
need intensive care for several days.
• External cooling—try to avoid ice as this 
may cause peripheral vasoconstriction and 
impede heat elimination; shivering response is 
also undesirable as this creates heat. • Fluid 
therapy—isotonic crystalloids can be 
administered at shock rates (dogs: 90 ml/
kg/h; cats: 45–60 mL/kg/h) based on clinical 
assessment; synthetic colloids may also be Heat Stroke and Hyperthermia

590  Blackwell’s Five-Minute Veterinary Consult  
Hused to treat shock (dogs: 20 mL/kg, 5 mL/kg 
IV boluses; cats: 5–10 mL/kg, 1–2 mL/kg 
boluses). • Oxygen supplementation—can be 
administered via mask, cage, or nasal cannula.
ACTIVITY
DIET
Nil PO until animal is stable.
• Be aware of clinical signs. • Know how to 
cool off animals. • Seek veterinary care 
immediately. • An episode of heat stroke may 
predispose pets to additional episodes.
T racheostomy may be required if upper 
airway obstruction is underlying cause or 
contributing factor.
• No specific drugs for hyperthermia or heat 
stroke; therapy dependent on clinical 
presentation. • Prophylactic broad ­spectrum 
antimicrobials may decrease incidence of 
bacterial translocation; first ­generation 
cephalosporins or potentiated penicillins 
(clavulanate/amoxicillin, sulbactam/
ampicillin) in combination with fluoroqui­
nolones provide excellent four ­quadrant 
coverage. • Acute renal failure—dopamine 
CRI (2–5  μg/kg/min), furosemide (2–4 mg/
kg IV PRN), mannitol 0.5–1 g/kg as slow IV/
CRI. • Cerebral edema—mannitol (1 g/kg 
IV over 15–30 min), furosemide (1 mg/kg 
IV) 30 min following mannitol infusion, 
corticosteroids: dexamethasone sodium 
phosphate (1–2 mg/kg IV), prednisone 
sodium succinate (10–20 mg/kg IV), methyl 
prednisolone (15 mg/kg IV); see Contra­
indications. • Ventricular arrhythmia— 
lidocaine bolus (2 mg/kg IV) followed by 
CRI (25–75  μg/kg/min); procainamide 
(6–8 mg/kg IV). • Metabolic acidosis—
sodium bicarbonate (0.3 × BW [kg] × base 
excess) give ⅓ to ½ as IV bolus. • DIC—
fresh frozen plasma (20 mL/kg); heparin 
doses vary widely (300–500 U/kg SC q 6–8h). • Thrombocytopenia—severe 
thrombocytopenia with active bleeding can 
be treated with fresh whole blood, platelet ­
rich plasma, lyophilized platelets, or frozen 
platelet concentrate. • Hematochezia or 
melena—broad ­spectrum antibiotics, 
H2­antagonists, or proton pump inhibitors in 
combination with sucralfate. • Seizures—
diazepam (0.5–1 mg/kg IV) or midazolam; 
phenobarbital (6 mg/kg IV PRN).
• Nonsteroidal anti ­inflammatory agents are 
not indicated in nonpyrogenic hyperthermia 
because the hypothalamic set point is not 
altered. • Corticosteroid use considered 
controversial in heat stroke due to possible 
adverse effects.
N/A
N/A
 FOLLOW-UP
• Patients should be closely monitored during 
cooling ­down period and for a minimum of 
24 hours post episode; most animals must be 
monitored for several days depending on 
clinical presentation and clinical complica­
tions. • Thorough physical examination 
should be performed daily; in addition the 
following parameters should be given 
consideration: ◦ Body temperature. ◦ Body 
weight. ◦ Blood pressure. ◦ Central venous 
pressure. ◦ ACT. ◦ PT/PTT. ◦ D­dimers. 
◦ ECG. ◦ Thoracic auscultation. ◦ Urinalysis 
and urine output. ◦ Packed cell volume, total 
protein. ◦ CBC, biochemical profile. ◦ Venous 
blood gas analysis (electrolytes, lactate).
• Cardiac dysrhythmias. • Organ failure. 
• Coma. • Seizures. • Acute renal failure. 
• DIC. • SIRS. • Sepsis/septic shock. 
• Pulmonary edema—acute respiratory 
distress syndrome (ARDS). • Rhabdomyolysis. 
• Hepatocellular necrosis. • Respiratory 
arrest. • Cardiopulmonary arrest.EXPECTED COURSE AND PROGNOSIS
• Depends on underlying cause or disease 
process. • Prognosis may depend on time lag 
between event and hospital admission. 
• Prognosis is guarded—dependent on 
complications (renal failure and DIC) and 
duration of episode. • May predispose animal 
to further episodes due to damage to 
thermoregulatory center.
SYNONYMS
• Heat exhaustion. • Heat prostration. 
• Heat ­related disease. • Heat stroke.
SEE ALSO
Fever
syndrome.
syndrome.
Bruchim Y, Klement E, Saragusty J, et al. 
Heat stroke in dogs: a retrospective study of 
54 cases (1999–2004) and analysis of risk 
factors for death. J Vet Intern Med 2006; 
20:38–46.
Gfeller R. Heat stroke. In: Ettinger SJ, 
Feldman EC, eds. Textbook of Veterinary 
Elsevier, 2005, pp. 437–440.
Johnson SI, McMichael M, White G. 
Heatstroke in small animal medicine: a 
clinical practice review. J Vet Emerg Crit 
Care 2006; 16(2):112–119.
available onlineHeat Stroke and Hyperthermia  (continued)

Canine and Feline, Seventh Edition  591
H BASICS
Helicobacter  spp. are microaerophilic, Gram-
negative, urease-positive bacteria ranging in 
shape from coccoid to curved to spiral.
Helicobacter  spp. in the Stomach
• The association of Helicobacter pylori  with 
gastritis, peptic ulceration, and gastric neoplasia 
fundamentally changed understanding of gastric 
disease in humans. • Putative mechanisms by 
which H. pylori  alters gastric physiology in 
humans include disruption of gastric mucosal 
barrier and alteration of gastric secretory 
activity. • H. pylori  in humans has been 
associated with increased secretion of 
proinflammatory cytokines and nitric oxide. 
• Several Helicobacter  spp. other than H. pylori  
have been isolated from stomachs of dogs and 
cats; typically, multiple species are present. • A 
possible cause–effect relationship of Helicobacter  
spp. and gastric inflammation in cats and dogs 
remains unresolved; inflammation or glandular 
degeneration accompanies infection in some 
but not all. • Experiments to determine 
pathogenicity of H. pylori  in specific pathogen 
free (SPF) cats and H. pylori  and H. felis  in 
gnotobiotic dogs demonstrated gastritis, 
lymphoid follicle proliferation, and humoral 
immune responses after infection.
Helicobacter  Spp. in the Liver 
and Intestines
• Role in intestinal and hepatic disease is 
unclear. • Several Helicobacter -like organisms 
(HLOs) have been identified in large intestine 
and feces from normal and diarrheic dogs and 
cats. • H. canis  has been isolated from liver of 
a dog with active, multifocal hepatitis.
Gastrointestinal (GI)— Helicobacter  spp. may 
lead to gastritis in some dogs and cats, diarrhea 
in some dogs with H. canis , possible acute 
GENETICS
N/A
Gastric Helicobacter  spp.
• Gastric HLOs are prevalent in dogs and 
cats—86–90% of clinically healthy cats, 
67–86% of clinically healthy pet dogs. • HLOs 
demonstrated in gastric biopsy specimens in 
57–76% of cats and 61–82% of dogs presented 
for investigation of recurrent vomiting. • To  
date H. pylori  has been identified only in a 
single colony of laboratory cats.
Enterohepatic Helicobacter  spp.
• H. canis  isolated in 4% of 1,000 dogs 
evaluated. • A single case of H. canis –
associated hepatitis reported in 2-month-old puppy. • Prevalence of H. fennelliae  and  
H. cinaedi  undetermined.
N/A
Species
Gastric infection acquired at a young age.
SIGNS
• Asymptomatic presence of Helicobacter  spp. 
common. • Vomiting, anorexia, abdominal 
pain, weight loss, and/or borborygmus have 
all been reported in dogs and cats with gastric 
Helicobacter  spp. • H. canis  in dogs may be 
associated with diarrhea. • Vomiting, 
weakness, and sudden death reported in 
puppy with hepatic H. canis .
• Usually unremarkable. • Dehydration due 
to vomiting or diarrhea.
CAUSES
• H. felis , H. heilmannii , and H. baculiformis  
have been identified in cats. • H. felis , H. 
bizzozeronii , H. salomonis , H. heilmannii , H. 
bilis, H. cynogastricus , and Flexispira rappini  
identified in dogs.
• H. bilis , H. canis , H. cinaedi , and Flexispira 
rappini  identified in feces from normal and 
diarrheic dogs. • H. cinaedi  identified in one 
cat; its significance is unknown. • H. canis  
reported in one dog with acute hepatitis.
Poor sanitary conditions and overcrowding 
may facilitate spread.
 DIAGNOSIS
• High prevalence of Helicobacter  spp. in dogs 
and cats. Therefore, exclusion of other causes 
of gastric disease and a positive identification 
of Helicobacter  spp. are crucial before a 
diagnosis of GI disease due to Helicobacter  spp. 
can be suspected. • Gastric helicobacteriosis—
distinguish from other causes of vomiting. 
• Intestinal helicobacteriosis—distinguish 
from other causes of diarrhea. • Hepatic 
helicobacteriosis—distinguish from other 
causes of hepatobiliary disease.
• May reflect fluid and electrolyte abnormalities 
secondary to vomiting and/or diarrhea. • May 
indicate hepatic disease in patients with H. 
canis–associated hepatitis.OTHER LABORATORY TESTS
• Examination of impression smears of gastric 
mucosa or gastric washings using May-
Grünwald-Giemsa, Gram, or Diff-Quik® 
stain is sensitive for Helicobacter  spp.; cannot 
distinguish between different HLOs. • Rapid 
urease test—requires gastric biopsy specimen. 
• 13C-urea breath or blood test reliable in 
identifying infected dogs; not commercially 
available. • Bacterial culture requires special 
techniques and media and is impractical. 
• PCR of DNA extracted from biopsy 
specimens or from gastric juice. • Serologic tests 
(ELISA) measure circulating immunoglobulin 
(Ig) G in serum; cannot distinguish between 
HLOs. • Histopathology enables definitive 
diagnosis of infection, but cannot distinguish 
between different HLOs.
IMAGING
Abdominal radiography, ultrasonography 
usually normal.
• Gastric helicobacteriosis—in cases of 
Helicobacter  spp.–associated gastritis, endoscopy 
may reveal superficial nodules that suggest 
hyperplasia of lymphoid follicles, diffuse gastric 
rugal thickening, punctate hemorrhages, 
erosions. • Hepatic helicobacteriosis—hepatic 
biopsy/histopathology (Warthin-Starry 
staining) and culture.
• Identification of HLOs requires special 
staining of tissue samples with Warthin-Starry 
or modified Steiner stain; routine H&E 
staining may reveal larger HLOs, but smaller 
organisms are often missed. • In cases of 
Helicobacter  spp.–associated gastric disease—
lymphocytic-plasmacytic gastritis and lymphoid 
follicle hyperplasia; rarely neutrophilic 
infiltrates; gastric ulcers have not been reported 
in dogs and cats. • In cases of H. canis –
associated hepatitis—hepatocellular necrosis; 
infiltration of hepatic parenchyma with 
mononuclear cells, and spiral-shaped to curved 
bacteria predominantly in biliary canaliculi.
 TREATMENT
• Pathogenicity of Helicobacter  spp. in dogs 
and cats is unclear; therefore, there are no 
generally accepted guidelines for treatment 
of HLO infections in dogs and cats. 
• Currently there is no indication for 
treating asymptomatic infected animals. 
• Eradication of gastric HLO should only 
be considered in infected dogs and cats that 
have compatible clinical signs that cannot 
be attributed to another disease process.
Fluid therapy in dehydrated patients.Helicobacter  spp.

592  Blackwell’s Five-Minute Veterinary Consult  
HDIET
Easily digestible diets in patients with GI 
disease signs.
Explain difficulty of establishing a definitive 
diagnosis, high prevalence of infections with 
HLOs in normal dogs and cats, potential for 
recurrence, and zoonotic potential, though 
minimal, of these infections.
• A triple therapy (combination of two 
antibiotics and one antisecretory drug) is 
effective in humans with H. pylori  infection, 
with cure rates of approximately 90%. 
• Combination therapy may eliminate 
Helicobacter  spp. infections in dogs and cats 
less effectively than in humans. • T reat for 
2–3 weeks.
Antibiotics (Two Antibiotics with One 
Antisecretory Agent)
• Clarithromycin (dogs: 5 mg/kg PO q12h; 
cats: 62.5 mg/cat PO q12h). • Metronidazole 
(dogs: 11–15 mg/kg PO q12h; cats: 
12.5 mg/kg PO q12h). • Amoxicillin 
(22 mg/kg PO q12h). • Azithromycin 
(5 mg/kg PO q24h). • Tetracycline (20 mg/
kg PO q8h). • Bismuth subsalicylate has 
mucosal protectant, anti-endotoxemic, and 
weak antibacterial properties; it remains 
unclear which property is responsible for its 
beneficial effects in HLO infections 
(0.22 mL/kg of 130 mg/15 mL solution of 
Pepto-Bismol PO q4–6h).
Antisecretory Agents (One with Two 
Antibiotics)
• Omeprazole (0.7–1 mg/kg PO q12h). 
• Famotidine (0.5 mg/kg PO q12–24h). 
• Ranitidine (1–2 mg/kg PO q12h).
Intestinal and Hepatic Helicobacter  spp. 
in Dogs
Combination of amoxicillin and 
metronidazole may be effective.
Hypersensitivity to drug therapy.ALTERNATIVE DRUG(S)
Patients with HLO infections and gastritis 
that do not respond to antibiotic therapy 
usually are given immunosuppressive therapy 
for inflammatory bowel disease with gastric 
 FOLLOW-UP
• Serologic tests not useful to confirm 
eradication of gastric HLOs—serum IgG 
titers may not decrease for up to 6 months 
after infection cleared. • If vomiting persists 
or recurs after cessation of combination 
therapy, endoscopic biopsy to determine 
whether infection has been successfully 
eradicated indicated.
Avoid overcrowding and poor sanitation.
• Efficacy of therapeutic regimens currently 
employed in dogs and cats for eradicating 
Helicobacter  spp. infections is questionable. 
• Metronidazole (20 mg/kg PO q12h), 
amoxicillin (20 mg/kg PO q12h), and 
famotidine (0.5 mg/kg PO q12h) for 14 days 
eradicated Helicobacter  spp. in 6 of 8 dogs when 
evaluated 3 days post treatment; all dogs were 
recolonized by day 28 after treatment. 
• Clarithromycin (30 mg/cat PO q12h), 
metronidazole (30 mg/cat PO q12h), ranitidine 
(20 mg/cat PO q12h), and bismuth subsalicylate 
(40 mg PO q12h) for 4 days were effective in 
eradicating H. heilmannii  in 11 of 11 cats by 
10 days; 2 cats were reinfected 42 days post 
treatment. • Amoxicillin (20 mg/kg PO q8h), 
metronidazole (20 mg/kg PO q8h), and 
omeprazole (0.7 mg/kg PO q24h) for 21 days 
transiently eradicated H. pylori  in 6 cats; all were 
reinfected 6 weeks post treatment. ( Note:  this 
dose of metronidazole has potential for toxicity.)
Other gastric diseases.AGE-RELATED FACTORS
Gastric HLOs appear to be acquired at a 
young age.
• High prevalence of Helicobacter  spp. in 
dogs and cats raises the possibility that 
household pets may serve as a reservoir for 
transmission of Helicobacter  spp. to human 
beings. • H. pylori , H. heilmannii , and  
H. felis  have been isolated from humans 
with gastritis. • H. fennelliae  and H. cinaedi  
have been isolated from immunocompromised 
humans with proctitis and colitis.  
• H. cinaedi  and H. canis  have been 
associated with septicemia in humans.  
• H. pylori  has not been identified in pet 
dogs or cats.
Avoid metronidazole and tetracycline in 
SYNONYMS
• Gastric spiral bacterial. • Gastrospirillum.
SEE ALSO
• HLO = Helicobacter- like organism.
• SPF = specific pathogen free.
Leib MS, Duncan RB, Ward DL. T riple 
antimicrobial therapy and acid suppression 
in dogs with chronic vomiting and gastric 
Helicobacter  spp. J Vet Intern Med 2007, 
21:1185–1192.
Simpson KW, Neiger R, DeNovo R, et al. 
The relationship of Helicobacter  spp. 
infection to gastric disease in dogs and cats. 
J Vet Intern Med 2000, 14:223–227.
Author  Jan S. Suchodolski
Jörg M. Steiner.
available onlineHelicobacter  spp.  (continued)

Canine and Feline, Seventh Edition  593
H
Hemangiopericytoma
  BASICS
OVERVIEW
• A soft tissue sarcoma (STS) arising around 
blood vessels in subcutaneous tissue. • Also 
known as perivascular wall tumor. • Locally 
invasive—microscopic disease often extending 
beyond gross visible tumor margins. 
• Metastasizes in less than 15% of patients 
with grade I/II (low/intermediate-grade) STS 
and less than 44% of patients with grade III 
(high-grade) STS.
• Common in dogs, rare in cats. • More 
common in large-breed than small-breed 
dogs. • Middle-aged to older dogs and cats.
SIGNS
• Typically, slow-growing, nonpainful, 
fluctuant to firm mass (weeks to months). 
• Rapid growth uncommon unless high-grade 
or associated with hemorrhage. • Local tumor 
growth can interfere with limb function.
• Subcutaneous soft tissue mass, more 
frequently located on extremity than on 
trunk. • Soft, fluctuant, or firm. 
• Nonpainful unless ulcerated or invading 
into deeper structures (muscle, nerve, bone). 
• Generally adhered to underlying tissue. 
• Regional lymph node metastasis 
uncommon.
Large-breed dogs at increased risk.
  DIAGNOSIS
• Other sarcomas such as fibrosarcoma, 
peripheral nerve sheath tumor, myxosarcoma, 
malignant fibrous histiocytoma, histiocytic 
sarcoma, hemangiosarcoma. • Lipoma and 
other subcutaneous tumors—benign and 
malignant.
IMAGING
• Thoracic radiographs recommended before 
treatment, although metastasis uncommonly 
identified. • Contrast-enhanced CT or MRI 
may be recommended to determine local 
extent of disease and optimize surgical 
treatment and radiation therapy planning.
• Fine-needle aspiration and cytology may 
provide tentative diagnosis, though cells do 
not exfoliate well given mesenchymal origin. • Incisional biopsy and histopathology may 
be used to confirm diagnosis, determine 
grade of tumor, and plan treatment 
approach. • Immunohistochemistry 
evaluation of biopsy can aid in 
differentiation from other mesenchymal 
tumors. • Regional lymph node evaluation 
(cytology or histopathology) appropriate for 
high-grade tumors or if regional 
lymphadenomegaly detected.
  TREATMENT
• Early, aggressive, en bloc surgical excision is 
treatment of choice. • Microscopically, cancer 
cells extend beyond gross tumor borders. 
• Pseudocapsule composed of compressed 
cancer cells is common. • Excise tumor en 
bloc; if peeled out, healthy bed of cancer cells 
(pseudocapsule) is left as residual disease. 
• Submit entire sample to pathologist for 
surgical margin evaluation; applying ink to 
surgical borders is advised. • Limb 
amputation may be necessary with tumors 
affecting appendicular extremities that may 
be otherwise unresectable. • Rib resection or 
abdominal wall resection may be required for 
tumors of trunk.
Radiation Therapy Considerations
• Adjuvant radiation therapy should be 
considered following either planned 
marginal resection or unplanned incomplete 
resection. • Radiation therapy most effective 
when directed at microscopic disease—
either preoperatively or as postoperative 
full-course fractionated protocol. • As single 
modality treatment for macroscopic disease, 
radiation therapy considered palliative—
may be used to decrease pain and slow 
tumor growth.
• Doxorubicin-based chemotherapy not 
consistently reported as beneficial, but 
remains recommended after excision of 
high-grade (grade III) tumor. • Low-dose 
chemotherapy (metronomic) with piroxicam 
and cyclophosphamide may help delay local 
recurrence when sarcoma incompletely 
resected. • Novel therapeutic options may be 
available—contact veterinary oncologist for 
potential updated treatments. • Analgesic 
therapy should be administered as needed if 
pain or discomfort present.
• If complete surgical resection achievable 
and tumor categorized as low-grade, tumor 
regrowth or metastases unlikely and 
continued patient monitoring may not be 
necessity. • If surgical resection incomplete or 
tumor categorized as high-grade, further 
treatment should be considered and patient 
should be monitored for local regrowth and 
distant metastases, with repeat physical exam 
and thoracic radiographs every 3 months.
• Local recurrence, metastasis, and overall 
survival time greatly affected by surgical margin 
assessment and histological grade. • Cure from 
disease possible when surgery aggressive and 
surgical margins tumor-free, especially with 
grade I and II tumors—median survival 
approaches 2 years with low-grade (I) STSs of 
extremities treated with surgery alone. • Local 
recurrence considered inevitable if treatment not 
aggressive; increased risk for metastatic disease 
especially with high-grade (III) tumors. • Long-  
term tumor control with radiation therapy after 
surgically debulking tumor gives 1–5-year 
control rates of 60–85%. • Incomplete surgical 
excision should be managed with either second 
aggressive surgery or radiation therapy as soon as 
possible; low-dosage chemotherapy 
(metronomic) is another option.
• STS = soft tissue sarcoma.
Bray JP . Soft tissue sarcoma in the dog – part 
1: a current review. J Small Anim Pract 
2016, 57:510–519.
Elmslie RE, Glawe P , Dow SW. Metronomic 
therapy with cyclophosphamide and 
piroxicam effectively delays tumor 
recurrence in dogs with incompletely 
resected soft tissue sarcomas. J Vet Intern 
Med 2008, 22:1373–1379.
Kuntz CA, Dernell WS, Poswers BE, et al. 
Prognostic factors for surgical treatment of soft 
tissue sarcomas in dogs: 75 cases (1986–1996). 
J Am Vet Med Assoc 1997, 211:1147–1151.
Stefanello D, Morello E, Roccabianca P , et al. 
Marginal excision of low-grade spindle cell 
sarcoma of canine extremities: 35 dogs 
(1996–2006). Vet Surg 2008, 37:461–465.
Author  Matthew R. Berry
editors acknowledge the prior contributions of 
Phyllis Glawe and Louis-Philippe de Lorimier.

594  Blackwell’s Five-Minute Veterinary Consult  
HHemangiosarcoma, Bone
  BASICS
OVERVIEW
• A highly metastatic malignant tumor of 
endothelial cell precursors. • Primary bone 
hemangiosarcoma (HSA) is rare and accounts 
for <5% of all canine bone tumors. • Can 
arise from various appendicular and axial 
sites—hind limb more common (78% tibial 
origin); rib most common axial location.
• Dogs, rarely cats. • Typically middle-aged to 
older dogs, older cats. • Predisposition for 
male dogs. • Golden retrievers, Labrador 
retrievers, and German shepherds predisposed.
SIGNS
• Appendicular: ◦ Pain/lameness. ◦ Soft 
tissue swelling/mass effect. ◦ Pathologic 
fracture. ◦ Axial: ◦ Thoracic wall mass. 
◦ Hemothorax. ◦ Spinal pain. ◦ Myelopathy 
(from vertebral body collapse, spinal cord 
compression).
• Dogs—genetic abnormalities including 
inactivation of the tumor suppressor gene 
PTEN ; overexpression of growth and 
apoptosis-related proteins RB, cyclin D1, 
Bcl2, and survivin; and overexpression of 
angiogenic factors such as vascular endothelial 
growth factor (VEGF) and angiopoietins. 
• Cats—none identified.
  DIAGNOSIS
• Radiography —lesions may appear similar to 
other primary or metastatic bone tumors or 
osteomyelitis (bacterial or fungal). 
• Histopathology —can be difficult to 
differentiate from telangiectatic subtype of 
osteosarcoma (OSA).
• Regenerative anemia. • Thrombocytopenia. 
• Neutrophilic leukocytosis.
IMAGING
• Musculoskeletal radiography —may reveal 
poorly marginated osteolytic lesion, often 
with minimal periosteal reaction; pathologic 
fractures possible; can be difficult to 
differentiate primary vs. metastatic lesions. 
• Thoracic radiography —used to screen for 
pulmonary metastasis, which typically appears 
as miliary to diffuse nodular pattern. 
• Abdominal and cardiac ultrasonography —
used to screen for primary and metastatic 
visceral tumors (spleen, liver, heart). • CT 
scan—can better define extent of bone tumor 
for surgical excision (especially axial lesions), more sensitive screening for pulmonary 
• Excisional biopsy is preferred method for 
diagnosis. • Incisional biopsy may yield a 
diagnosis, but due to the vascular nature of 
the tumor, blood contamination within the 
specimen may preclude a diagnosis or prevent 
differentiation between HSA and telangiec-
tatic OSA.
• Gross findings —a dark, friable mass often 
within the medullary cavity of the bone; 
metastasis can be multifocal, including lungs, 
spleen, liver, kidneys, muscle, peritoneum. 
• Histopathology —anaplastic mesenchymal 
cells arranged in chords forming vascular 
channels and spaces filled with red blood 
cells, thrombi, and necrotic debris.
  TREATMENT
• Wide margin surgical excision is treatment 
of choice. • Amputation recommended for 
appendicular lesions. • Axial tumors may be 
more difficult to resect. • Palliative (hypofrac-
tionated) radiation therapy may be used to 
control pain and swelling. • Adjuvant 
doxorubicin chemotherapy is indicated due to 
high metastatic potential.
• Doxorubicin—dogs: 30 mg/m2 IV >15 kg; 
1 mg/kg IV <15 kg, q2–3 weeks for 5 cycles; 
cats: 1 mg/kg IV q3 weeks for 5 cycles. 
• Metronomic cyclophosphamide (12.5–
15 mg/m2 PO q24h) in combination with a 
nonsteroidal anti-inflammatory drugs 
(NSAID; e.g., piroxicam 0.3 mg/kg PO q24h) 
may be used concurrent to doxorubicin and/or 
as long-term maintenance therapy following 
doxorubicin. • Vincristine (0.5–0.7 mg/m2) 
and cyclophosphamide (200–250 mg/m2) q21 
days can be used in rescue settings.
Alternative Drug(s)
• Bioactive extract (polysaccharide peptide) 
made from Coriolus versicolor  mushroom may 
have benefit in dogs with HSA. • Chinese 
herbal remedy yunnan baiyao may have 
anti-bleeding and anti-neoplastic benefit for 
patients with has; however, was proven 
ineffective for HSA effusions.
• Doxorubicin administration can lead to 
acute gastrointestinal, bone marrow, cardiac, 
renal, hypersensitivity, and extravasation toxicities. • Doxorubicin can lead to 
cumulative cardiotoxicity in dogs; dogs with 
preexisting cardiac disease or breeds at risk for 
dilated cardiomyopathy should be screened 
with echocardiogram/ECG before, during, 
and after treatment with doxorubicin. 
• Metronomic cyclophosphamide can lead to 
sterile hemorrhagic cystitis in ~22–58% of 
dogs, but risk can be significantly reduced 
(<10%) with use of concurrent furosemide. 
• NSAIDs can lead to gastrointestinal and 
liver/kidney toxicity.
  FOLLOW-UP
• Periodic physical examination, labwork, 
thoracic radiography, and abdominal 
ultrasonography during and after completion 
of therapy. • If treated with metronomic 
cyclophosphamide chemotherapy, monthly 
urinalysis recommended to screen for sterile 
hemorrhagic cystitis.
• Pathologic fracture. • Bone lesions (esp. 
within rib) and visceral metastatic lesions may 
rupture, resulting in clinical signs related to 
effusion and/or anemia.
• Aggressive disease with high risk for 
metastasis. • Less than 10% of patients 
survive 1 year following surgery alone. 
• T reatment with amputation and chemo-
therapy is associated with median overall 
survival of ~10 months (range: 4 months–2 
years). • Younger age and more aggressive 
treatment are associated with longer survival.
• HSA = hemangiosarcoma. • NSAID = 
nonsteroidal anti-inflammatory drug. • OSA 
= osteosarcoma. • VEGF = vascular 
endothelial growth factor.
Giuffrida MA, Kamstock DA, Selmic LE, et al. 
Primary appendicular hemangiosarcoma and 
telangiectatic osteosarcoma in 70 dogs: a 
Veterinary Society of Surgical Oncology 
retrospective study. Vet Surg 2018, 
47:774–783.
Mullin CM, Clifford CS. Hemangiosarcoma. 
In: Withrow SJ, Vail DM, Thamm DH, 
Liptak J, eds. Small Animal Clinical 
Oncology, 6th ed. St. Louis, MO: Saunders/
Elsevier, 2019, pp. 773–777.
Authors  Christine Mullin and Craig A. Clifford

Canine and Feline, Seventh Edition  595
HHemangiosarcoma, Heart
  BASICS
OVERVIEW
• Highly metastatic malignant tumor of 
endothelial cell precursors • Most common 
cardiac tumor in dogs. • Can be primary or, less 
commonly, metastatic site. • Most tumors 
involve right atrium or right auricular appendage.
• Dogs, rarely cats. • German shepherds, 
Labrador retrievers, golden retrievers 
predisposed. • Typically middle-aged to older 
animals. • Predisposition for male dogs.
SIGNS
• Signs most commonly related to pericardial 
effusion, cardiac tamponade, secondary 
right-sided congestive heart failure. • Historical 
findings —collapse, lethargy, weakness, exercise 
intolerance, anorexia, cough, dyspnea, 
vomiting. • Physical examination findings —
muffled heart and lung sounds, arrhythmias, 
pulse deficits, pulsus paradoxus, pale mucous 
membranes, jugular vein distention, abdominal 
distension with effusion, hepatomegaly.
Dogs—genetic abnormalities including 
inactivation of tumor suppressor gene PTEN ; 
overexpression of growth and apoptosis-
related proteins RB, cyclin D1, Bcl2, 
survivin; overexpression of angiogenic factors 
such as vascular endothelial growth factor 
(VEGF) and angiopoietins.
  DIAGNOSIS
• Other cardiac neoplasia. • Idiopathic 
hemorrhagic pericardial effusion. • Other 
causes of right heart failure and arrhythmias.
• Poikilocytosis—acanthocytes, schistocytes, 
spherocytes. • Neutrophilic leukocytosis.
• Coagulation panel (prothrombin time [PT], 
partial thromboplastin time [PTT], D-dimers, 
fibrinogen)—criteria for disseminated intra -
vascular coagulation (DIC) present in up to 
50% of patients. • Plasma cardiac troponin 
(cTnI) levels elevated in dogs with pericardial 
effusion secondary to hemangiosarcoma (HSA) 
and can help differentiate from pericardial 
effusion not caused by HSA.
IMAGING
• Thoracic radiography —may reveal presence 
of globoid cardiac silhouette, pleural effusion, 
pulmonary metastasis, characterized by 
miliary to diffuse nodular pattern. • Abdominal ultrasonography —can screen for 
primary or metastatic hepatosplenic lesions, 
omental nodules, free abdominal fluid 
(hemoabdomen). • Echocardiography —useful 
for identifying and guiding removal of 
pericardial effusion and determining location 
and extent of tumor involvement (tumor 
better visualized when effusion present).
• Definitive diagnosis requires tissue biopsy. 
• Thoracoscopy can be used to perform 
pericardiectomy and obtain biopsies; 
thoracoscopic tumor resection also 
infrequently performed. • Cytologic 
evaluation of pericardial fluid rarely provides 
definitive diagnosis due to hemodilution and 
lack of tumor cell exfoliation. • ECG may 
reveal arrhythmias and electrical alternans.
• Gross findings —hemorrhagic friable mass in 
right side of heart; metastasis can be multifocal, 
including lungs, spleen, liver, kidneys, 
muscle, peritoneum. • Histopathology 
findings —anaplastic mesenchymal cells 
arranged in chords forming vascular channels 
and spaces filled with red blood cells, 
thrombi, necrotic debris.
  TREATMENT
• Periodic pericardiocentesis can provide 
temporary symptomatic relief from cardiac 
tamponade. • Thoracoscopic pericardectomy 
(pericardial window) can be performed as 
palliative procedure to lower risk of life-
threatening cardiac tamponade. • Surgical 
tumor excision provides best chance of 
long-term tumor control, but restricted to 
tumors on atrial appendage and/or small areas 
of right atrial wall. • Use of doxorubicin 
chemotherapy in measurable disease setting 
associated with >40% objective tumor 
response rate and provides clinical benefit in 
almost 70%.
• Doxorubicin (30 mg/m2 IV for dogs 
>15 kg; 1 mg/kg IV for dogs <15 kg) q2–3 
weeks for 5 cycles. • Metronomic 
cyclophosphamide (12.5–15 mg/m2 PO 
q24h) in combination with nonsteroidal 
anti-inflammatory drug (NSAID; e.g., 
piroxicam 0.3 mg/kg PO q24h) may be used 
concurrent to or as alternative to doxorubicin.
Bioactive extract (polysaccharide peptide) 
from Coriolus versicolor  mushroom may have 
benefit in dogs with HSA.CONTRAINDICATIONS/POSSIBLE 
renal, hypersensitivity, extravasation toxicities. 
• Doxorubicin can lead to cumulative cardio -
toxicity in dogs; those with preexisting cardiac 
disease or at risk for dilated cardio  myopathy 
should be screened with echocardiogram/
ECG before, during, and after treatment with 
doxorubicin. • Metronomic cyclophosphamide 
can lead to sterile hemorrhagic cystitis in 
~22–58% of dogs, but risk can be significantly 
reduced (<10%) with use of concurrent 
furosemide. • NSAIDs can lead to gastro -
intestinal toxicity and liver/kidney toxicity.
  FOLLOW-UP
thoracic radiography, abdominal ultrasonography 
during and after completion of therapy. • If 
treated with metronomic cyclophosphamide 
chemotherapy, monthly urinalysis recommended 
to screen for sterile hemorrhagic cystitis.
• Prognosis guarded to poor, high risk of 
acute death due to cardiac tamponade or fatal 
arrhythmias. • Median survival ~2 weeks 
without treatment, ~4 months with 
doxorubicin, possibly longer if tumor 
resection performed.
• cTnI = cardiac troponin. • DIC = 
nonsteroidal anti-inflammatory drug.  
• PT = prothrombin time. • PTT = partial 
thromboplastin time. • VEGF = vascular 
Mullin CM, Arkans MA, Sammarco CD, 
et al. Doxorubicin chemotherapy for 
presumptive cardiac hemangiosarcoma in 
dogs. Vet Comp Oncol 2016, 
14(4):e171–e183.

596  Blackwell’s Five-Minute Veterinary Consult  
H
Hemangiosarcoma, Skin
  BASICS
endothelial cell precursors.
• Primary tumor develops within dermal or 
subcutaneous/intramuscular tissues.
• Accounts for ~14% of all hemangiosarcomas 
(HSAs) in dogs.
• Metastatic risk dependent upon grade and 
location within the tissues (stage).
• Subcutaneous/intramuscular lesions may 
represent metastasis from a primary visceral 
tumor.
• Pit bulls, boxers, and German shepherds.
• Dermal hemangiosarcoma—whippet, 
greyhound, and related breeds.
• Median age 9 years.
SIGNS
Dermal
• Firm, raised, dark nodules on the limbs, 
head, face, nasal planum, ears, ventral 
abdomen, and inguinal region.
• When caused by UV radiation, lesions often 
appear as multiple small blood blisters on the 
ventral abdomen/inguinal region.
Subcutaneous/Intramuscular
• Usually solitary lesions.
• Firm to fluctuant masses with associated 
discoloration and/or bruising from 
intratumoral bleeding.
• Pelvic limbs are commonly affected, but 
tumors may arise in any location.
• In cats—the flank, ventral abdomen, 
inguinal region, and cervical region are most 
commonly affected sites.
• Dermal HSA is associated with UV 
radiation via induction of actinic keratosis, 
especially along the ventral abdomen/inguinal 
region in sparsely haired and lightly 
pigmented dogs that sunbathe.
• Subcutaneous HSA may be secondary to 
prior ionizing radiation therapy.
  DIAGNOSIS
• T rauma-induced subcutaneous  
hematoma.
• Other sarcomas.
• Mast cell tumor.
• Regenerative anemia.
• Neutrophilic leukocytosis.OTHER LABORATORY TESTS
Coagulation panel (prothrombin time [PT], 
fibrinogen)—may see changes compatible 
with disseminated intravascular coagulation 
(DIC) if large, bleeding subcutaneous/
intramuscular tumor.
IMAGING
• Thoracic radiography — used to screen for 
pulmonary metastasis, which typically 
appears as a miliary to diffuse nodular 
pattern.
• Ultrasonography —abdominal 
ultrasonography should be performed to 
screen for metastatic (or primary) hepato -
splenic lesions, omental nodules, and free 
abdominal fluid (hemoabdomen); focal 
ultrasound of the mass may reveal 
cavitations.
• Echocardiography —can be used to identify 
right atrial masses.
• Advanced imaging —MRI/CT can be used 
for staging and surgical planning purposes, 
particularly for larger subcutaneous/
intramuscular tumors.
Cytology
• Often unrewarding due to insufficient cell 
numbers and blood contamination.
• Neoplastic cells are spindle to stellate with 
anisocytosis and anisokaryosis, single round, 
oval, pleomorphic nuclei with prominent 
nucleoli, low nuclear cytoplasmic ratio, and 
moderate to abundant basophilic and usually 
vacuolated cytoplasm.
• Gross findings —well-circumscribed, 
blood blister–like lesions confined to 
the dermis or more invasive, poorly 
circumscribed hemorrhagic tumors within 
the subcutaneous and intramuscular space; 
metastasis can be multifocal including 
lungs, spleen, liver, kidneys, muscle, 
• Histopathologic findings —anaplastic 
mesenchymal cells arranged in chords 
forming vascular channels and spaces filled 
with red blood cells, thrombi, and necrotic 
debris.
⚬ Allows differentiation between 
hemangioma and HSA and dermal  
versus subcutaneous/intramuscular  
origin.
⚬ Immunohistochemistry for von 
Willebrand factor (factor VIII–related 
antigen) or CD31/platelet endothelial cell 
adhesion molecule (PECAM) can be used 
to confirm endothelial cell origin.
Histologic Staging System
• Stage I—confined to dermis.
• Stage II—subcutaneous involvement.
• Stage III—intramuscular involvement.  TREATMENT
• Wide margin surgical excision is the 
treatment of choice.
• Definitive radiation therapy may be used 
for the control of microscopic residual disease 
(incomplete margins after resection of 
subcutaneous/intramuscular tumors).
• Palliative (hypofractionated) radiation 
may be used for treatment of nonresectable 
tumors and ~60% of patients will have a 
positive response for a median of 3 months.
• Doxorubicin chemotherapy has been 
associated with a moderate response rate 
(~40%) for a median of ~2 months, but in 
some cases may allow for complete tumor 
resection and longer remission/survival.
• Metronomic (daily low-dose) chemotherapy 
can be used to delay time to locoregional 
recurrence after surgery given its anti-
angiogenic effect.
cats: 1 mg/kg IV q3 weeks for 5 cycles.
• Metronomic cyclophosphamide  
(12.5–15 mg/m2 PO q24h) in combination 
with a nonsteroidal anti-inflammatory drug 
(NSAID; e.g., piroxicam 0.3 mg/kg PO 
q24h) may be used concurrent to doxorubicin 
and/or as a long-term maintenance therapy 
following doxorubicin.
• Vincristine (0.5–0.7 mg/m2) and 
cyclophosphamide (200–250 mg/m2) q21 
renal, hypersensitivity, and extravasation 
toxicities.
• Doxorubicin can lead to cumulative 
cardiotoxicity in dogs; dogs with preexisting 
cardiac disease or those breeds at risk for 
and after treatment with doxorubicin.
dogs, but the risk can be significantly reduced 
(<10%) with the use of concurrent furosemide.
• A bioactive extract (polysaccharide peptide) 
made from the Coriolus versicolor  mushroom 
may have benefit in dogs with HSA.

Canine and Feline, Seventh Edition  597
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• The Chinese herbal remedy yunnan baiyao 
may have anti-bleeding and anti-neoplastic 
benefit for patients with HSA; however, this 
was proven ineffective for HSA effusions.
  FOLLOW-UP
of therapy.
• If treated with metronomic cyclophosphamide 
N/A
T umor hemorrhage.
• Dermal HSA—prognosis very good with 
treatment; median survival time (MST) of 
780–987 days for dogs undergoing surgery 
alone; disease-free interval >450 days for cats 
undergoing surgery alone.
• Higher risk of locoregional recurrence and 
distant metastasis with stage II (SC) and III 
(IM) HSA.• Subcutaneous HSA—prognosis can be 
good with aggressive treatment; MST of 172 
days for dogs undergoing surgery alone versus 
>1,100 days with surgery and adjuvant 
doxorubicin chemotherapy.
• Intramuscular HSA—MST of 272 days for 
dogs undergoing surgery and doxorubicin 
Other UV-induced skin tumors such as 
squamous cell carcinoma.
N/A
• HSA = hemangiosarcoma.
• MST = median survival time.• NSAIDs = nonsteroidal anti-inflammatory 
drugs.
• PECAM = platelet endothelial cell adhesion 
molecule.
Bulakowski EJ, Philibert JC, Siegel S, et al. 
Evaluation of outcome associated with 
subcutaneous and intramuscular 
hemangiosarcoma treated with adjuvant 
doxorubicin in dogs: 21 cases (2001–
2006). J Am Vet Med Assoc 2008, 
233:122–128.
Johannes CM, Henry CJ, T urnquist SE, et al. 
Hemangiosarcoma in cats: 53 cases 
(1992–2002). J Am Vet Med Assoc 2007, 
231:1851–1856.
Ward H, Fox LE, Calderwood-Mays MB, 
et al. Cutaneous hemangiosarcoma in 25 
dogs: a retrospective study. J Vet Intern Med 
1994, 8:345–348.
Clifford
Consulting Editor  Timothy M. Fan(continued)  Hemangiosarcoma, Skin

598  Blackwell’s Five-Minute Veterinary Consult  
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Hemangiosarcoma, Spleen and Liver
  BASICS
A highly metastatic malignant tumor of 
• Spleen is most common primary tumor 
location; liver is fourth most common location.
• Primary tumor rupture leads to acute 
hemorrhage, collapse, and often sudden 
death.
• Highly metastatic tumor that spreads early 
in the course of disease via hematogenous and 
intra‐abdominal implantation routes.
• Metastasis can be to any organ including 
lungs, kidneys, muscle, peritoneum, 
omentum, lymph nodes, mesentery, adrenal 
glands, spinal cord, brain, subcutaneous 
tissue, and diaphragm.
• Hepatobiliary.
• Nervous.
• Renal.
GENETICS
N/A
Accounts for 50–70% of all canine splenic 
tumors.
N/A
• Dogs, rarely cats.
• German shepherd, Labrador retriever, 
golden retriever predisposed.
• Typically middle‐aged to older animals.
• Possible slight predisposition for male dogs.
SIGNS
• Historical findings —can be variable and 
include weakness, lethargy, dyspnea, cough, 
inappetance, and weight loss.
• Physical examination findings —pale mucous 
membranes, arrhythmias, tachypnea, 
abdominal distension, and palpable cranial 
abdominal mass.
CAUSES
N/A
apoptosis‐related proteins RB, cyclin D1, 
growth factor (VEGF), endothlein‐1, and 
angiopoietins.
• Cats—none identified.  DIAGNOSIS
• Anticoagulant rodenticide ingestion.
• Other splenic and hepatic masses—
hematoma, hemangioma, hepatoma, 
lymphoma, leiomyosarcoma, liposarcoma, 
splenic cyst, hepatocellular carcinoma, hepatic 
cyst, hepatic abscess.
• Regenerative anemia with nucleated red 
blood cells.
spherocytes.
partial thromboplastin time [PTT], D‐dimers, 
fibrinogen)—criteria for disseminated 
intravascular coagulation (DIC) present in up 
to 50% of patients.
IMAGING
• Abdominal radiographs may identify a 
cranial abdominal mass and loss of serosal 
detail consistent with peritoneal effusion.
• Thoracic radiographs are used to screen for 
as a miliary to diffuse nodular pattern.
• Abdominal ultrasonography is used for the 
detection of hepatosplenic lesions, omental 
nodules, and free abdominal fluid (hemo- 
abdomen).
• Echocardiography is used to identify right 
atrial masses (better visualized when 
pericardial effusion is present).
• MRI/CT provide high sensitivity and 
specificity in determining benign from 
malignant processes of the liver and spleen; 
more sensitive method of screening for 
• Abdominocentesis —usually a serosang -
uineous or hemorrhagic nonclotting effusion; 
can compare packed cell volume (PCV) of 
effusion to peripheral blood PCV to confirm 
• Cytology —often unrewarding due to 
insufficient cell numbers and blood 
contamination; neoplastic cells are spindle 
to stellate with anisocytosis and 
anisokaryosis, single round, oval, 
pleomorphic nuclei with prominent 
moderate to abundant basophilic and 
usually vacuolated cytoplasm.PATHOLOGIC FINDINGS
• Gross findings —solitary or multiple 
hemorrhagic, friable masses or nodules within 
the spleen and/or liver.
◦ Stage I—tumor confined to one organ, 
no rupture.
◦ Stage II—ruptured tumor.
◦ Stage III—measurable metastatic disease.
• Histopathology findings — anaplastic 
debris; immunohistochemistry for von 
adhesion molecule (PECAM) can be used to 
confirm endothelial cell origin.
  TREATMENT
• Balanced isotonic electrolyte solutions ± 
colloids to correct hypovolemic shock and 
reduced cardiac output.
• Fresh whole blood or packed red blood 
cell transfusions to replace reduced oxygen‐
carrying capacity lost by acute hemorrhage.
• Fresh frozen plasma if coagulopathy or 
signs of DIC present.
N/A
ACTIVITY
N/A
DIET
N/A
N/A
• Splenectomy or liver lobectomy is the 
standard of care surgical procedure and initial 
treatment of choice; removes macroscopic 
tumor burden and lessens the ongoing risk of 
acute death from hemorrhage.
• The use of adjuvant doxorubicin‐based 
chemotherapy has been consistently shown to 
improve remission duration and survival 
times.
• Adjuvant metronomic chemotherapy 
appears to prolong survival vs. surgery alone. 
Added benefit when given concurrent to or 
following doxorubicin chemotherapy remains 
unclear.
>15 kg, 1 mg/kg IV for dogs <15 kg, q2–3 
weeks for 5 cycles) alone or as part of a

Canine and Feline, Seventh Edition  599
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protocol with weekly vincristine (0.5–7 mg/
m2 IV) and cytoxan (250 mg/m2 PO) or 
dacarbazine (200–250 mg/m2 IV q24h for 5 
days or 600–1000 mg/m2 IV bolus q3 weeks)
nonsteroidal anti‐inflammatory drug (NSAID; 
e.g., piroxicam 0.3 mg/kg PO q24h) may be 
used concurrent to or as an alternative to 
doxorubicin.
N/A
cardiotoxicity in dogs; those with preexisting 
cardiac disease or breeds at risk for dilated 
cardiomyopathy should be screened with 
echocardiogram/ECG before, during, and 
after treatment with doxorubicin.
• Vincristine and dacarbazine administration 
can lead to acute gastrointestinal, bone 
marrow, and extravasation toxicities
(<10%) with the use of concurrent 
furosemide.
• NSAIDs can lead to gastrointestinal toxicity 
and liver/kidney toxicity.
N/A
may have benefit in dogs with 
hemangiosarcoma (HSA).• The Chinese herbal remedy yunnan baiyao 
may have anti‐bleeding and anti‐neoplastic 
  FOLLOW‐UP
ultrasonography during and after the 
completion of therapy.
• If treated with metronomic chemotherapy, 
routine monthly urinalysis recommended to 
screen for sterile hemorrhagic cystitis.
N/A
Death due to acute hemorrhage or fatal 
• Prognosis poor to grave.
• Less than 10% of dogs will live 1 year or 
longer from diagnosis.
• Median survival time with surgery alone 
(dogs): 1–3 months.
• Median survival time with surgery plus 
chemotherapy (dogs): 4.5–8 months.
N/A
N/A
SYNONYMS
N/A
• NSAIDs = nonsteroidal anti‐inflammatory 
drugs.
molecule.
• VEGF = vascular endothelial growth 
factor.
Alvarez FJ, Hosoya K, Lara‐Garcia A, et al. 
VAC protocol for treatment of dogs with 
stage III hemangiosarcoma. J Am Anim 
Hosp 2013, 49:370–377.
Finotello R, Stefanello D, Zini E, et al. 
Comparison of doxorubicin‐
cyclophosphamide with doxorubicin‐
dacarbazine for the adjuvant treatment of 
canine hemangiosarcoma. Vet Comp Oncol 
2017, 15:25–35.
Clifford
Consulting Editor  Timothy M. Fan(continued)  Hemangiosarcoma, Spleen and Liver

600  Blackwell’s Five-Minute Veterinary Consult  
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Hematemesis
  BASICS
Vomiting of blood.
A disruption in the gastric or upper small 
intestinal mucosal barrier leading to 
inflammation and bleeding. Coagulopathies 
can also present with hematemesis. An animal 
may also vomit blood that originated in the oral 
cavity or respiratory system and was swallowed.
• Gastrointestinal (GI)—inflammation, 
trauma, ulceration, neoplasia, and/or foreign 
body in oral cavity, pharyngeal area, esophagus, 
stomach, and/or duodenum. • Cardiovascular—  
acute, severe hemorrhage may result in 
tachycardia and hypotension. • Hematologic—  
coagulopathy with GI hemorrhage can lead 
to hematemesis. • Respiratory—respiratory 
hemorrhage with ingestion can lead to 
hematemesis.
GENETICS
N/A
Unknown
Species
None
Any age.
Male dogs have increased incidence of gastric 
SIGNS
• Vomiting with blood, which may appear as 
fresh blood, blood clots, or digested blood 
(looks like coffee grounds). • Melena. 
• Anorexia. • Abdominal pain.
• Abdominal pain. • Melena. • If patient is 
anemic—tachycardia, heart murmur, pallor, 
weakness.
CAUSES
Coagulopathies
• Thrombocytopenia. • Thrombocytopathia. 
• Von Willebrand’s disease. • Hyperviscosity 
syndrome. • Disseminated intravascular 
coagulation. • Anticoagulant rodenticide 
toxicity. • Coagulation factor deficiency. 
• Liver failure.
Drugs
Nonsteroidal anti-inflammatory drugs (NSAIDs), 
glucocorticoids, toceranib phosphate.GI Diseases
• Inflammatory bowel disease. • Gastric or 
duodenal neoplasia. • Gastric or duodenal 
foreign body. • Gastric or intestinal volvulus. 
• Hemorrhagic gastroenteritis. • Gastroduodenal 
ulcer. • Gastroesophageal intussusception.
Toxicity
• Heavy metal poisoning (arsenic, zinc, 
thallium, iron, or lead). • Plant intoxication 
(dieffenbachia, sago palm, mushroom, castor 
bean). • Chemical intoxication (phenol, 
ethylene glycol, corrosive agents, psoriasis 
creams—vitamin D analogues). • Pesticide/
rodenticide toxicity (cholecalciferol). • Snake 
bite. • Aflatoxins. • Bee sting.
• GI parasitism. • Pythiosis. • Viral, fungal, 
or bacterial gastroenteritis. • Virulent 
systemic feline calicivirus. • Rickettsial 
• Renal failure. • Liver disease. • Hypoadreno -
corticism. • Pancreatitis.
Neoplasia
• Mastocytosis. • Gastrinoma. • Oral, nasal, 
respiratory, or GI tumors. • Amine precursor 
uptake decarboxylase cells (APUDomas).
Neurologic Diseases
• Head trauma. • Spinal cord disease.
Respiratory Diseases
• Nasal disease. • Pulmonary disease. 
• Mediastinal neoplasia.
• Shock. • Severe illness. • Burns. • Heat 
stroke. • Major surgery. • Sustained 
strenuous exercise. • T rauma. • Systemic 
hypertension. • Thromboembolic disease. 
• Administration of ulcerogenic drugs. 
• Critically ill patients. • Shock. • Thrombo -
cytopenia. • Concurrent administration of 
NSAIDs and glucocorticoids.
  DIAGNOSIS
• Hemoptysis—thoracic radiographs may 
reveal presence of pulmonary disease. 
• Regurgitation or vomiting of  swallowed 
blood from extra-GI diseases (e.g., 
oropharyngeal, nasopharyngeal, cutaneous). 
• Vomiting materials that look like fresh or 
digested blood (e.g., oral iron).
• If acute (3–5 days) blood loss—  
nonregenerative anemia. • If blood loss >5–7 
days in duration—regenerative anemia. • If 
chronic blood loss—iron-deficiency anemia 
(microcytic, hypochromic, variable reticulocytosis, with or without thrombo -
cytosis). • ± thrombocytopenia.  
• ± panhypoproteinemia. • ± mature 
neutrophilia or left-shift neutrophilia with 
sepsis and/or gastroduodenal ulcer 
perforation. • Blood urea nitrogen (BUN) : 
creatinine ratio may be elevated with GI 
• Fecal occult blood test—often false positive 
if not on nonmeat diet for 3 days prior to test. 
• Fecal flotation—screen for GI parasitism. 
• Coagulation profile—if coagulopathy is 
suspected. • Bile acids—if liver disease is 
suspected. • Adrenocorticotropic hormone 
(ACTH) stimulation—if hypoadrenocorti -
cism suspected.
IMAGING
• Abdominal radiographs may identify 
gastric or duodenal foreign body or mass, 
pneumoperitoneum, effusion, or changes 
consistent with kidney, pancreas, or liver 
disease. • Thoracic radiographs may reveal 
esophageal foreign body or mass, gastro -
esophageal intussusception, mediastinal 
mass, pulmonary disease, or pulmonary 
metastasis. • Abdominal ultrasonography 
may identify gastric or duodenal mass, 
gastric or duodenal wall thickening or 
altered layering, gastric ulcer, and/or 
abdominal lymphadenopathy. • Abdominal 
ultrasonography can also screen for 
abnormalities in pancreas, liver, kidneys, 
and other abdominal organs as source of 
hematemesis. • GI scintigraphy may be 
used to localize blood loss.
• Endoscopy to evaluate mucosal appearance 
of esophagus, stomach, and upper small 
intestinal tract once extra-GI causes ruled 
out. • Capsule endoscopy may be useful to 
identify sites of GI hemorrhage. • Biopsy 
mucosal lesions to determine nature of 
underlying GI disease. • Abdominocentesis 
may identify septic peritonitis. • Fine-needle 
aspirates or biopsy of organs or masses to 
identify neoplasia/disease.
• Gastroduodenal inflammation and 
hemorrhage. • Ulcers may have necrosis, 
microthrombi, and hemorrhage.
  TREATMENT
• T reat underlying cause. • Outpatient—
those in which the cause is identified and 
removed, vomiting is not excessive, and 
gastroduodenal bleeding is minimal. 
• Inpatients—those with severe 
gastroduodenal bleeding, ulcer perforation, 
excessive vomiting, and/or shock.

Canine and Feline, Seventh Edition  601
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• IV fluids to maintain volume and hydration. 
• Hypoproteinemic patients may require colloids 
and/or albumin to increase oncotic pressure. 
• Anemic or coagulopathic patients may require 
transfusion. • In severe cases—to stop the GI 
bleeding, ice water lavage (10–20 mL/kg 
remaining in stomach for 15–30 min) or lavage 
with norepinephrine (8 mg/500 mL) diluted in 
ice water can be attempted.
ACTIVITY
Restriction is indicated until resolution.
DIET
• Discontinue oral intake if vomiting. 
• When feeding is resumed, feed small, 
frequent meals.
• NSAIDs should be administered to pets 
only under the guidance of a veterinarian. 
• NSAIDs and glucocorticoids should not be 
administered together. • Adverse effects of 
NSAIDs can be reduced by giving drug with 
food and concurrent administration of a 
synthetic prostaglandin E1 analogue (e.g., 
misoprostol).
Surgery is indicated if medical treatment fails 
after 5–7 days, hemorrhage is uncontrolled, 
gastroduodenal ulcer perforates, and/or 
potentially resectable tumor is identified.
• Proton pump inhibitors (PPIs)—most 
potent inhibitors of gastric acid secretion and 
treatment of choice for gastroduodenal ulcer 
(dog and cat: omeprazole 1 mg/kg PO q12h; 
pantoprazole or esomeprazole 1 mg/kg IV 
q12h - esomeprazole may be superior for first 
72 hours of therapy. • Histamine (H2) receptor 
antagonists also inhibit gastric acid secretion 
(dog and cat: famotidine 0.5–1 mg/kg PO/IV 
q12–24h); famotidine with a loading dose of 
1 mg/kg followed by 8 mg/kg IV CRI daily 
for 3 consecutive days may be superior to 
pantoprazole. • H2 receptor antagonists are 
less potent than PPIs. • Sucralfate suspension 
(dog and cat: 0.25–1 g PO q6–8h) protects 
ulcerated tissue by binding to ulcer sites, 
adsorbing pepsin and bile salts, and stimulating 
prostaglandin synthesis; binding is greater in 
duodenal than gastric ulcers. • Antibiotic(s) 
with activity against enteric Gram-negative 
bacteria and anaerobes should be given 
parenterally if a break in GI mucosal barrier is 
suspected or aspiration pneumonia is present. 
• Antiemetics—dog and cat: chlorpromazine 0.5 mg/kg q6–8h SC/IM/IV, prochlorperazine 
0.1–0.5 mg/kg q6–8h SC/IM, ondansetron 
0.2–0.5 mg/kg IV q12h, maropitant 1 mg/kg 
SC/IV q24h; dog: metoclopramide 1–2 mg/
kg/24h CRI, administered if vomiting occurs 
frequently or results in significant fluid losses.
Avoid ulcerogenic drugs such as NSAIDs and 
Continued famotidine therapy can lead to 
tachyphylaxis.
• H2 blockers prevent uptake of omeprazole 
by oxyntic cells. • Sucralfate may alter 
absorption of other drugs and should be given 
2 hours before or after other oral drugs. 
• Antacids may alter oral absorption and 
renal elimination of other drugs.
Misoprostol, synthetic prostaglandin analogue 
(3 μg/kg PO q12h) with antisecretory and 
cytoprotective actions helps prevent NSAID-
induced ulcers. There may be some efficacy in 
treating gastroduodenal ulcerations from 
other causes.
  FOLLOW-UP
• Improvement in some cases may be assessed 
on resolution of clinical signs; packed cell 
volume, total protein, fecal occult blood, and 
BUN may help detect continued blood loss. 
• Depending on the underlying cause of the 
hematemesis, specific laboratory or imaging 
tests may be necessary to monitor response to 
therapy.
• Avoid gastric irritants (e.g., NSAIDs, 
corticosteroids). • Concurrent use of 
misoprostol or PPI with NSAIDs; PPIs may 
be preferable because they are therapeutic as 
well. • Administer NSAIDs with food. 
• Cyclooxygenase (COX)-2 selective or dual 
lipoxygenase/COX inhibitors may have fewer 
adverse GI effects than nonselective NSAIDs.
• Anemia. • Hypovolemia. • Ulcer 
perforation. • Sepsis.
• Varies with underlying cause. • Patients 
with malignant gastric neoplasia, renal failure, 
liver failure, pythiosis, systemic mastocytosis, 
sepsis, and/or gastric perforation—guarded to 
poor prognosis. • Hematemesis secondary to NSAID administration, coagulopathies, 
inflammatory bowel disease, or hypoadreno -
corticism—prognosis may be good to 
excellent, depending on severity of disease. 
• Hematemesis secondary to heat stroke, 
toxicities, and snake bites can have variable 
prognoses.
Anemia
Synthetic prostaglandins (e.g., misoprostol) 
cause abortion.
SEE ALSO
• Melena.
• APUDoma = amine precursor uptake 
decarboxylase cells.
Case V. Melena and hematochezia. In: 
Veterinary Internal Medicine Diseases of the 
Dog and Cat, 7th ed. St. Louis, MO: 
Saunders Elsevier, 2010, pp. 203–206.
Kuhl A, Odunayo A, Price J, et al. 
Comparative analysis of the effect of IV 
administered acid suppressants on gastric 
pH in dogs. J Vet Intern Med.2020:1–6. 
https://doi.org/10.1111/jvim.15718
Neiger R. Gastric ulceration. In: Bongura 
JD, T wedt DC, eds. Kirk’s Current 
Elsevier Saunders, 2014, e251–e255.
Tolbert K, Bissett S, King A, et al. Efficacy 
of oral famotidine and 2 omeprazole 
formulations for the control of intragastric 
pH in dogs. J Vet Intern Med 2011, 
25:47–54.
Author  Jocelyn Mott
Consulting Editor  Mark P . Rondeau(continued)  Hematemesis

602  Blackwell’s Five-Minute Veterinary Consult  
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Hematuria
  BASICS
Blood in urine.
Secondary to loss of endothelial integrity in 
urinary tract, clotting factor deficiency, or 
thrombocytopenia/cytopathia.
• Renal/urologic. • Reproductive. • Hemic/
lymphatic/immune.
• Dog and cat. • Familial hematuria in young 
animals; neoplasia in older animals. • Females 
at greater risk for urinary tract infection (UTI).
SIGNS
Red-tinged urine with or without pollakiuria.
• Palpable mass in patients with neoplasia. 
• Abdominal pain in some patients. 
• Enlarged and/or painful prostate gland in 
males. • Petechiae or ecchymoses in patients 
with coagulopathy.
CAUSES
Systemic
• Coagulopathy. • Thrombocytopenia. 
• Vasculitis.
Upper Urinary Tract
• Anatomic—cystic kidney disease and 
familial malformations. • Metabolic—
nephrolithiasis. • Neoplastic—renal 
lymphoma, adenocarcinoma, and 
hemangiosarcoma. • Infectious—
leptospirosis, feline infectious peritonitis 
(FIP), and bacterial or fungal UTI. 
• Inflammatory—glomerulonephritis. 
• Idiopathic renal hematuria. • T rauma.
Lower Urinary Tract
• Anatomic—bladder malformations. 
• Metabolic—uroliths. • Neoplasia—
transitional cell carcinoma and lymphosarcoma. 
• Infectious—bacterial, fungal, and viral 
UTI. • Idiopathic—cats (idiopathic cystitis). 
• T raumatic. • Cyclophosphamide-induced 
Genitalia
• Metabolic—estrus, benign prostatic 
hyperplasia. • Neoplastic—transmissible 
venereal tumor (TVT), leiomyoma, and 
prostatic adenocarcinoma. • Infectious—
bacterial and fungal disease. • Inflammatory—
prostatitis. • T rauma.
Breed predisposed to urolithiasis, 
coagulopathy, or neoplasia.  DIAGNOSIS
See Figure 1.
Other causes of discolored urine (myoglobinuria, 
hemoglobinuria, and bilirubinuria).
Substantial doses of vitamin C (ascorbic acid) 
may cause false-negative reagent test strip 
results; newer generations of reagent strips are 
more resistant to interference by reducing 
substances such as ascorbic acid.
Results
• Common urine reagent strip tests for blood 
are designed to detect red blood cells, 
hemoglobin, or myoglobin. • Low urine 
specific gravity (polyuric syndromes) lyses red 
blood cells (RBCs). • Bacteriuria (bacterial 
peroxidase) causes false-positive reagent test 
strip results. • Formalin preservative causes 
false-negative reagent test strip results.
Valid if Run in a Human Laboratory?
Yes
• Thrombocytopenia and severe anemia in 
some patients. • Azotemia in some patients 
with bilateral renal disease. • RBCs ( >5–10 
RBC/hpf) and possibly infectious agents seen 
in urine sediment. • Crystalluria in some 
patients with urolithiasis.
• Coagulation testing to rule out coagulopathy. 
• Bacterial culture of urine to identify UTI. 
• Examination of ejaculate to identify 
prostatic disease.
IMAGING
Ultrasonography, radiography, and possibly 
contrast radiography are useful in localizing 
the underlying cause. Cystoscopy often 
required to diagnose renal hematuria.
• Biopsy of mass lesion. 
• Vaginourethrocystoscopy in females or 
urethrocystoscopy in males and females.
  TREATMENT
• Hematuria may indicate a serious disease 
process. • Urolithiasis and renal failure may 
require diet modification. • UTI may be 
associated with another disease that also requires 
treatment—local (e.g., neoplasia and urolithiasis) 
or systemic (e.g., hyperadrenocorticism and 
diabetes mellitus). • Renal hematuria may be 
treated via endoscopic sclerotherapy; 
nephrectomy should not be performed.  MEDICATIONS
• Blood transfusion if patient is severely 
anemic. • Antibiotics to treat UTI and 
septicemia. • Heparin for disseminated 
intravascular coagulation (DIC).
Immunosuppressive drugs, except to treat 
immune-mediated disease.
Intravenous contrast media may cause acute 
kidney injury.
  FOLLOW-UP
Depends on primary or associated diseases.
• Anemia. • Hypovolemia if severe 
hemorrhage. • Ureteral or urethral 
obstruction due to blood clots.
• Neoplasia tends to occur in older animals. 
• Immune-mediated diseases tend to occur in 
young adult animals.
SEE ALSO
• Coagulation Factor Deficiency. • Crystalluria. 
• Cylindruria. • Dysuria, Pollakiuria, and 
Stranguria. • Feline Idiopathic Lower Urinary 
T ract Disease. • Glomerulonephritis. 
• Hemoglobinuria and Myoglobinuria. 
• Lower Urinary T ract Infection, Bacterial. 
• Lower Urinary T ract Infection, Fungal. 
• Nephrolithiasis. • Prostatitis and Prostatic 
Abscess. • Prostatomegaly. • Proteinuria. 
• Pyelonephritis. • Thrombocytopenia.
• FIP = feline infectious peritonitis. • RBC = 
red blood cell. • TVT= transmissible venereal 
tumor. • UTI = urinary tract infection.
Bartges JW. Discolored urine. In: Ettinger SJ, 
Elsevier, 2008, pp. 164–168.
Author  Joseph W. Bartges

Canine and Feline, Seventh Edition  603
H
Red, br own, or b lack urine
Occult blood neg ative
Bilirubin
Porphyrins
Other sOccult blood positiv e
Urine sediment examination
No RBCs RBCs
Lower ur inary
tract signs
Female or
castrat ed maleHx trauma
Male:  palpat e
prostat e
Normal Abnor mal
Abnor mal
TVT
Estrus
Vaginitis
Vaginal smear
Cultur eVariable pain
Prostatic h yperplasia
Prostatic neoplasia
Prostatic cy sts
Prostatic metaplasia
Radiograph y
Ultrasonograph y
Ejaculat e examination
Cultur e
Biops y
Painful
Prostatitis
Prostat e abscess
Cultur e
Aspiration/Biops yNormal
Cystitis
Urethritis
Uroliths
Neoplasia
Bladder malf ormation
Urine cultur e
Biops yMild or
absent
proteinur iaSevere proteinuria
Glomer ulonephr itis
Urine Protein:cr eatinine
24-hour pr otein
Biops y
Abnor malities
Neoplasia
Nephr oliths
Ureteroliths
Cysto renal
diseaseNo abnor malities
Drugs
Coagulopath y
Renal trauma
Idiopathic r enal hematur ia
Telangiectasia of Welsh cor gis
Vascular diseaseRadiograph y
IVP
Ultrasonograph yNormal ser um color Pink color to serum
Hemoglobin
Ammonium sulf ate
test or pr otein
electr ophor esis
Negative
RBC lysis in ur ine
Positiv e
MyoglobinNo lo wer ur inary
Examine external genitaliaNo Hx
trauma
Pyuria present
Upper UTI with or
without
nephr olithsPyuria absent
IVP
Ultrasonograph yDrugs
Dyes
Figure 1 .
Algorithm for the diagnosis of red, brown, or black urine.(continued)  Hematuria

604  Blackwell’s Five-Minute Veterinary Consult  
H
Hemoglobinuria and Myoglobinuria
  BASICS
Hemoglobinuria—presence of free hemoglobin 
(HGB) within urine secondary to intravascular 
hemolysis. Myoglobinuria—presence of 
myoglobin (MGB) within urine secondary to 
myocyte injury or death. Presence of either 
protein causes discoloration of urine 
(pigmenturia) as well as positive blood result 
during reagent test strip analysis of urine, a 
semiquantitative measurement of heme.
• Hemoglobinuria —intravascular hemolysis or 
destruction of RBCs within vessels releases 
HGB from damaged red blood cells (RBCs). 
HGB, if free within plasma, can cause tissue 
injury. Haptoglobin, protein made by the liver, 
acts as HGB recovery system and binds free 
HGB. Resulting HGB–haptoglobin complexes 
too large to be cleared by glomerular filtration 
and so are removed primarily by splenic 
macrophages. Excessive intravascular hemolysis 
can saturate haptoglobin, resulting in free 
HGB in plasma, known as hemoglobinemia. 
Free HGB (4 heme-containing chains, 64,000 
daltons) rapidly dissociates into unstable 
dimers (32,000 daltons) and passes freely 
through glomerular basement membrane 
leading to hemoglobinuria. Hemoglobinuria 
imparts pink, dark amber, red, or red-brown 
discoloration to urine. Methemoglobinemia 
causes analogous disease process.
• Myoglobinuria —MGB is single heme-
containing chain (approximately 17,500 
daltons). MGB able to carry oxygen without 
oxidation of ferrous (Fe2+) to ferric (Fe3+) iron 
due to interaction of heme with protein 
portion (globin). Myocyte injury and/or death 
releases MGB. Unlike free HGB, MGB is 
freely and rapidly cleared by glomerulus given 
its small size and absence of carrier protein, so 
plasma remains colorless even in face of 
significant myocyte death. Myoglobinuria 
causes brown or red-brown discoloration to 
urine.
• Renal tubular injury —presence of excess 
HGB or MGB in renal tubular fluid may 
result in kidney injury. Within tubules, acidic 
environment favors HGB or MGB precipita-
tion, cast formation, and tubular obstruction. 
Both HGB and MGB are endocytosed by 
renal tubular epithelial cells. Globin, from 
HGB, is degraded within the cell, while free 
heme is catabolized by heme oxygenase, 
resulting in lipid peroxidation and Fe 
deposition. MGB also causes lipid peroxida-
tion, but without release of free iron (via 
redox cycling of heme center). Alkaline 
conditions reported to prevent MGB-induced 
lipid peroxidation by stabilizing reactive ferryl 
MGB complex and also decreasing MGB 
precipitation in renal tubules. Free HGB also scavenges nitric oxide, leading to vasocon-
striction of afferent renal arteriole and 
secondary hypoperfusion and ischemic injury.
Renal/urologic—HGB, methemoglobin, and 
MGB can result in tubular injury, especially 
with concurrent decreased renal perfusion 
and acidic conditions.
GENETICS
Some predispositions relating to breeds; see 
Signalment.
N/A
N/A
Dog
• Hemoglobinuria secondary to phospho -
fructokinase (PFK) deficiency in affected 
spaniel, English cocker spaniel, cocker 
spaniel, wachtelhund, whippet.
• Hemoglobinuria uncommonly seen in 
Bedlington terriers with inherited copper 
toxicosis and copper release from hepatocytes 
• Myoglobinuria secondary to exertional 
myopathy or rhabdomyolysis in racing sled 
dogs and greyhounds.
• Pigmenturia rarely reported secondary to 
exertional lactic acidosis in English sheepdog.
Cat
Hemoglobinuria secondary to neonatal 
isoerythrolysis in neonatal blood type A or 
AB kittens born to blood type B queens.
SIGNS
Clinical signs diverse and related to specific 
causes; see Causes.
Patient breed, exposure to certain drugs or 
foreign objects, and recent exertion 
particularly important; see Causes.
• Findings associated with hemolytic anemia 
may include pale mucous membranes, 
tachycardia, icterus.
• Findings associated with muscle damage may 
include muscle tenderness, swelling, bruising.
CAUSES
Hemoglobinuria
• Oxidative RBC injury—drugs (acetami-
nophen, benzocaine, vitamin K3, new 
methylene blue, phenacetin, phenazopyri-
dine, monensin); food (onions, garlic); heavy 
metals (copper, zinc in pennies minted before 
1982 and zinc-containing sunscreens, diaper 
cream, hardware or toys).
• Physical RBC injury—severe burns, heat 
stroke, crush injury, electric shock, IV hypotonic fluid administration, shearing or microangiopathy 
due to disseminated intravascular coagulopathy, 
D. immitis  caval syndrome.
• Toxin-induced RBC membrane damage—
snake or spider venom; Shiga  toxin in 
hemolytic uremic syndrome.
• Infection of RBCs—dogs: babesiosis; cats: 
Mycoplasma hemofelis  infection, Cytauxzoon felis .
• Systemic infection—leptospirosis, E. coli  or 
other Shiga  toxin-producing bacteria causing 
hemolytic uremic syndrome, bacterial 
• Immune-mediated RBC destruction—  
idiopathic or secondary immune-mediated 
hemolytic anemia, incompatible blood 
transfusions in dogs or cats, neonatal 
isoerythrolysis.
• Deficiencies—hypophosphatemia.
• Genetic associated—PFK deficiency, copper 
toxicity.
• Other—retroperitoneal hemorrhage, trans -
fusion of inappropriately stored RBC units.
Myoglobinuria
• Exertional—extreme exercise.
• Myositis—infectious (e.g., toxoplasmosis, 
neosporosis), eosinophilic inflammatory 
(German shepherd dog, other breeds), 
immune mediated.
• Genetics-associated—X-linked muscular 
dystrophy; glycogenoses (storage diseases); 
mitochondrial abnormalities.
• Toxins (loss of membrane integrity)—snake 
or spider venom.
• Physical—ischemia, crush injury, 
compartment syndrome.
• Excessive body temperature (e.g., heat 
stroke, prolonged seizures).
• Genetic predisposition (see Signalment).
• Exposure to specific drugs, toxins.
• Certain infectious agents.
• Extreme physical exertion.
• Snake or spider venom.
  DIAGNOSIS
• Pigmenturia can result from hematuria, 
hemoglobinuria, methemoglobinuria, or 
myoglobinuria. Positive heme reaction of 
urine reagent test strip detects heme portion 
in intact RBCs, free HGB, and free MGB. 
Use of CBC, biochemical, and urinalysis 
results can aid in differentiation.
• Hematuria—supported by increased (>5/hpf) 
RBCs in urine sediment examination and clear 
plasma or serum.
• Hemoglobinuria—supported by <5/hpf 
RBCs in urine sediment, red or pink plasma 
or serum, indicating hemoglobinemia, 
anemia, RBC inclusions, or poikilocytes, 
supporting cause for hemolytic anemia,

Canine and Feline, Seventh Edition  605
H
hyperbilirubinemia, and bilirubinuria.
• Methemoglobinuria—supported by dark 
brown or chocolate-colored whole blood; 
often accompanies hemoglobinemia and 
hemoglobinuria.
• Myoglobinuria—supported by absence of 
RBCs in urine sediment, clear plasma or serum, 
increased creatine kinase (CK) and aspartate 
aminotransferase (AST), often normal packed 
cell volume (PCV), normal bilirubin.
• False-positive results.
False-Positive Heme Urine Reagent 
Strip (Dipstick) Results
• Urine contact with bleach or hydrogen 
peroxide.
• Highly pigmented urine or marked 
• Large amounts of bromide or iodide.
• Bacteriuria.
False-Negative Heme Urine Reagent 
• Urine exposure to formalin.
• Patients taking captopril or ascorbic acid 
(Vitamin C).
• Failure to mix urine specimen prior to 
chemical/dipstick reagent testing or using 
supernatant for testing.
Results
Hyposthenuria or exposure of urine to extreme 
cold or heat in patients with hematuria may 
cause in vitro RBC lysis (no intact RBCs in 
sediment) with positive heme urine reagent 
dipstick reaction; could be misinterpreted as 
hemoglobinuria or myoglobinuria.
Yes
• Intravascular hemolysis and 
hemoglobinuria:
 ◦CBC support includes anemia, which 
may be preregenerative or regenerative 
depending on onset of hemolysis, RBC 
ghost cells, RBC inclusions (Heinz bodies 
to support oxidative injury, infectious 
agents), RBC poikilocytes (eccentrocytes 
and pyknocytes support oxidative injury, 
spherocytes support immune-mediated 
mechanisms, schistocytes support 
 microangiopathic causes, some toxins), 
possibly increased mean cell HGB 
concentration (MCHC) or discrepant 
increase in HGB concentration from 
hemoglobinemia, red-colored plasma. ◦Chemistry support includes red-colored 
serum or plasma, hyperbilirubinemia.
 ◦Urinalysis support includes absence of 
hematuria, possible proteinuria.
• Rhabdomyolysis and myoglobinuria:
 ◦CBC changes not expected.
 ◦Chemistry findings include markedly 
increased (>4–5 × upper reference limit 
[URL]) CK with slower increases in AST; 
plasma and serum expected to be clear.
 ◦Urinalysis findings include absence of 
• Ammonium sulfate precipitation test 
unreliable and recommendation to use CBC 
and chemistry changes for differentiation.
• Incubation of whole blood with new 
methylene blue to detect Heinz bodies.
• Methemoglobin detection confirms toxin as 
oxidant.
• Increased serum copper or zinc 
• DNA test for PFK deficiency.
IMAGING
Abdominal radiographs or ultrasound—
metallic objects in gastrointestinal tract.
• Liver biopsy and copper quantification.
• Genetic testing for PFK.
  TREATMENT
• IV fluid therapy to maintain renal perfusion.
• Avoid hyperventilation in PFK-deficient 
patients.
• See Causes for specific treatments.
Vary with underlying cause.
N/A
  FOLLOW-UP
PCV, urinalysis and urine sediment, serum 
creatinine, CK, urine production.
Renal tubular injury may develop.  MISCELLANEOUS
Neonatal isoerythrolysis.
N/A
SYNONYMS
Pigmenturia
SEE ALSO
• AST = aspartate aminotransferase
• CK = creatine kinase
• HGB = hemoglobin
• MCHC = mean cell HGB concentration
• MGB = myoglobin
• PCV = packed cell volume
• PFK = phosphofructokinase
• RBC = red blood cell
• URL = upper reference limit.
Bartges JW. Hematuria and other conditions 
causing discolored urine. In: Ettinger SJ, 
Elsevier, 2010, pp. 164–168.
Owen JL, Harvey JW. Hemolytic anemia in 
dogs and cats due to erythrocyte enzyme 
deficiencies. Vet Clin North Am Small 
Anim Pract 2012, 42(1):73–84.
Shelton DG. Rhabdomyolysis, myoglobinu -
ria, and necrotizing myopathies. Vet Clin 
North Am Small Anim Pract 2004, 
34:1469–1482.
Sink C, Weinstein NM. Routine urinalysis: 
chemical analysis. In: Sink C, Weinstein 
NM, Practical Veterinary Urinalysis. 
Ames, IA: Wiley Blackwell, 2012, 
pp. 42–45.
Stockham SL, Scott SA. Erythrocytes. In: 
Fundamentals of Veterinary Clinical 
Pathology, 2nd ed. Ames, IA: Blackwell, 
2008, pp. 112–192.
Author  Nicole M. Weinstein
of Cheryl L. Swenson, Carl A. Osborne, and 
Eugene E. Nwaokorie.(continued)  Hemoglobinuria and Myoglobinuria

606  Blackwell’s Five-Minute Veterinary Consult  
H
Hemothorax
  BASICS
OVERVIEW
• Accumulation of blood in pleural space. 
• Can develop acutely due to trauma or a 
coagulopathy, or neoplasia; may also be 
chronic. • Cardiovascular and respiratory 
systems commonly affected.
Any age, breed, or sex of dog and cat; 
younger dogs more commonly affected with 
anticoagulant rodenticide and trauma, older 
dogs more commonly affected with cancer.
SIGNS
• Peracute to acute onset—hypovolemic signs 
can occur before sufficient blood volume 
accumulates in the pleural space to impair 
respiration. • In chronic cases, larger volumes 
of blood may accumulate. • Respiratory 
distress, tachypnea; honking cough is possible 
in dogs with rodenticide poisoning; ecchy-
moses along ventral cervical and thoracic inlet 
areas. • Pale mucous membranes. • Weakness 
and collapse. • Weak, rapid pulse.
• T rauma—bleeding artery or vein of the 
thoracic wall, mediastinum, or thoracic spine; 
damaged heart, lungs, thymus, or diaphragm; 
herniated abdominal viscera (liver or spleen). 
• Neoplasia—involving any structure adjacent 
to the pleural cavity; rib tumors are particularly 
common. • Coagulopathies—can be congeni -
tal or acquired; rodenticide ingestion common. 
• Lung lobe torsion. • Acute thymic hemor -
rhage in young animals. • Dirofilaria immitis , 
Spirocerca lupi , Angiostrongylus vasorum .
  DIAGNOSIS
• Nonhemorrhagic pleural effusions—  
chylothorax; pyothorax; modified transudates; 
transudates. • Congestive heart failure.
• PCV and hemoglobin—reflect blood loss 
after initial fluid compartment shifts have 
occurred. • Platelet count may be low 
(~100,000) with acute blood loss. • Very low 
platelet count ( <20,000) consistent with 
spontaneous bleeding, although thrombocyto -
penia alone rarely represents in hemothorax.
• Hemorrhage-produced effusion—packed 
cell volume (PCV) and protein content 
similar to that of peripheral blood; platelets 
commonly seen on cytology. • Inflammation- or vascular-congestion related effusion—PCV 
<8%. • Neoplasia or lung lobe torsion—PCV 
can be low or mid-range. • Cytologic exam -
ination—often fails to identify malignant 
causes, but is recommended.
Coagulation Tests
• Prolonged prothrombin time (PT)/partial 
thromboplastin time (PTT) suggestive of 
coagulopathy. • Specific factor analysis—
needed to diagnose congenital defect or 
acquired coagulopathy. • Buccal mucosal 
bleeding time—identifies platelet function 
defect or vasculitis.
IMAGING
• Radiology—reveals pleural effusion varying 
from diffuse increase in radiopacity to ventral 
leafing, interlobar fissures, and localized 
pleural densities. • Can see associated lesions 
(e.g., rib fractures or tumors, pneumothorax 
or pneumomediastinum, mediastinal 
hemorrhage, pulmonary contusions, 
diaphragmatic lesions, and masses). • Lobar 
consolidation with vesicular gas pattern 
suggestive of lung lobe torsion. • In stable 
patients without coagulopathy—evacuation 
of pleural space may allow better radiographic 
visualization of masses or other pathology.
• Thoracentesis (contraindicated if clotting 
abnormality). • CT to evaluate for neoplasia 
or lung lobe torsion.
  TREATMENT
• Acute—judicious use of IV fluids; try to get 
systolic blood pressure above 90 mmHg using 
crystalloids and/or hypertonic saline to 
correct hypovolemia. • Coexisting pneumo-
thorax—generally requires needle thoracente-
sis or tube thoracostomy. • Plasma, specific 
clotting factors, and/or blood transfusion can 
be needed to restore clotting factors or 
provide red blood cells (RBCs) for oxygen 
transport. • Pulmonary contusion—may 
require ventilator support. • Severe or 
recurrent thoracic hemorrhage—may require 
surgical exploration. • Oxygen therapy.
• Most coagulopathic cases have respiratory 
difficulty associated with soft tissue bleeding 
rather than pleural hemorrhage and therefore 
rarely require evacuation of pleural fluid to 
resolve tachypnea. • Autotransfusion.
• Hypovolemia—see Shock, Hypovolemic. 
• Vitamin K1—5 mg/kg SC loading dose 
(using small-gauge needle) followed by 1.5–2.5 mg/kg PO q12h for 21–30 days; 
takes 12 hours or more to carboxylate clotting 
factors and restore activity. • Analgesics—  
systemically or as nerve blocks for trauma. 
• Broad-spectrum antibiotics— when 
Avoid aspirin and other nonsteroidal 
  FOLLOW-UP
• Clinical signs, respiratory rate and effort, 
heart rate. • Temperature. • Urine 
production. • Relief from pain. • Follow-up 
radiographs at 48-hour intervals until 
stable. • Coagulation panel in 48 hours if 
coagulopathy due to anticoagulant 
rodenticide toxicity diagnosed, and 48 
hours after discontinuing vitamin K 
• Pyothorax. • Sepsis. • Entrapment and 
constriction of lungs by scar tissue and 
fibrosis.
• Peritonitis—with penetrating wounds 
(e.g., gunshot) into the abdomen. 
SEE ALSO
• Lung Lobe Torsion. 
• Pleural Effusion. 
• Pulmonary Contusions. 
• Rodenticide Toxicosis—Anticoagulants.
drug. • PCV = packed cell volume. • PT = 
prothrombin time. • PTT = partial thrombo -
plastin time. • RBC = red blood cell.
Berry CR, Gallaway A, Thrall DE, Carlisle 
C. Thoracic radiographic features of 
anticoagulant rodenticide toxicity in 
fourteen dogs. Vet Radiol Ultrasound 
1993, 34:391–396.
Nakamura RK, Rozanski EA, Rush JE. 
Non-coagulopathic spontaneous hemotho-
rax in dogs. J Vet Emerg Crit Care 2008, 
18:292–297.
Author  Bradley L. Moses

Canine and Feline, Seventh Edition  607
HHemotropic Mycoplasmosis
  BASICS
OVERVIEW
Red blood cell (RBC) destruction and anemia 
caused by bacterial attachment to the external 
surface of RBCs, nutrient scavenging by bacteria 
from RBC, and immune response by the host.
• Acute disease most common in young cats, 
chronic form most common in adults.
• More common in outdoor and male cats.
• Acute disease in splenectomized dogs, 
chronic disease in nonsplenectomized dogs.
• Kennel-raised beagles at increased risk for 
• No sex prevalence in dogs.
SIGNS
Cats
• For Mycoplasma haemofelis  infection:
 ◦Variable disease severity ranging from 
inapparent infection (chronic disease) to 
marked anemia and death (acute disease).
 ◦Intermittent fever (50% of the time) 
during the acute phase, depression, weakness, 
anorexia, anemia, pale mucous membranes, 
splenomegaly, and (occasionally) icterus.
• For Candidatus M. haemominutum  
infection:
 ◦Usually results in inapparent infection.
 ◦Minimal or no decrease in hematocrit.
• For Candidatus M. turicensis :
 ◦Limited information regarding natural 
 ◦Mild anemia following experimental 
Dogs
• Mild or inapparent signs (e.g., pale mucous 
membranes and listlessness)—except when 
dogs have been splenectomized or splenic 
function is altered.
• High prevalence of chronic, inapparent 
infection in kennel-raised beagles, which may 
threaten validity of research results.
• Caused by bacteria previously classified in 
the genus Haemobartonella , these organisms 
are now recognized to be mycoplasmas 
(hemotropic mycoplasmas or hemoplasmas) 
based on genetic determination,
• M. haemofelis  (previously classified as large 
form of H. felis ), M. haemominutum  (previously 
classified as small form of H. felis ), and M. 
haemocanis  (previously classified as H. canis ).
• M. haemofelis  infection in cats gener -
ally causes more severe disease than 
M.  haemominutum  or Candidatus M. 
turicensis  infection.
• Cats—anemia more severe if feline 
leukemia virus (FeLV) infected.• Dogs—likelihood of severe anemia greatly 
increased if splenectomized or with pathologic 
changes in the spleen.
  DIAGNOSIS
• Other causes of hemolytic anemia, including 
immune-mediated hemolytic anemia (IMHA), 
babesiosis (not in cats in the United States), 
cytauxzoonosis (cats only), Heinz body 
hemolytic anemia (new methylene blue can 
be used to identify Heinz bodies), micro -
angiopathic hemolytic anemia, pyruvate 
kinase deficiency, and phosphofructokinase 
deficiency (dogs only).
• Differentiated from IMHA only by 
recognition of parasites in blood (stained blood 
film or species-specific PCR-based assays); 
both disorders (IMHA and/or M. haemofelis  
infection) may be Coombs’ test positive.
• Babesia  and Cytauxzoon  species are protozoal 
organisms that differ in morphology from 
mycoplasma.
• Enzyme assays or specialized DNA tests can 
be used to diagnose pyruvate kinase and 
phosphofructokinase deficiencies.
• Anemia most often present with reticulocy-
tosis in animals with clinically important 
infections—may appear poorly regenerative if 
precipitous decrease in packed cell volume 
(PCV) has occurred early in the disease or if 
there are other concurrent disorders (e.g., 
FeLV or feline immunodeficiency virus [FIV] 
infection in cats).
• Autoagglutination may be seen in feline 
blood samples after they cool to below body 
• Hyperbilirubinemia may be measured and/
or seen clinically at times but is seldom severe.
• Substantial bilirubinuria seen in some dogs.
• Abnormalities related to anemic hypoxia 
may be shown by clinical chemistry profiles, 
but profile can be normal.
• Hypoglycemia possible in moribund cats 
or if slow to separate blood cells from plasma 
or serum.
• Routine blood stains (e.g., Wright-Giemsa) 
to identify organisms in blood films.
• Organism may detach from RBCs in stored 
blood anticoagulated with EDTA.
• Reticulocyte stains cannot be used to 
identify Mycoplasma  organisms because 
punctate reticulocytes in cats appear similar 
to the parasites.
• Organisms must be differentiated from 
precipitated stain, refractile drying, or fixation 
artifacts, poorly staining Howell-Jolly bodies, 
and basophilic stippling.• Feline organisms—small blue-staining cocci, 
rings, or rods on RBCs, often many parasites 
for M. haemofelis ; small rods or coccoid 
organisms in low numbers for Candidatus M. 
haemominutum ; parasites not conclusively 
seen in blood for Candidatus M. turicensis .
• Canine organisms—commonly form chains 
of organisms that appear as filamentous 
structures on the surface of RBCs.
• Infection is cyclic and thus organisms are not 
always identifiable in blood (especially in cats).
• PCR-based assays can detect parasites in 
blood below the number required to make a 
diagnosis by a stained blood film.
• In patients with nonregenerative anemia, 
bone marrow biopsy should be performed to 
detect other disorders.
• PCR testing of blood donor cats and dogs 
is strongly recommended.
  TREATMENT
• Without therapy, mortality with M. 
haemofelis  infection may reach 30% in cats.
• Outpatient treatment unless severely 
anemic or moribund.
• Blood transfusions required when anemia is 
considered life-threatening.
• Shock should be treated with IV 
administration of isotonic crystalloid fluids, 
with or without glucose supplementation.
• Doxycycline (5 mg/kg PO q12h) should be 
given for minimum of 4 weeks.
• If PCR remains positive or bacteremia 
reoccurs after doxycycline therapy,  antibiotic 
treatment should be switched to marbofloxacin 
(2 mg/kg PO q24h) for 2 weeks.
• Esophageal strictures and gastrointestinal 
disease have been reported in cats following 
doxycycline administration.
• Fluroquinolones, including marbofloxacin, 
may cause arthropathy in young dogs and 
retinotoxicity in cats.
  FOLLOW-UP
• Examine animal after 1 week of treatment 
to confirm that PCV has risen.
• Alert owners that cats may remain carriers even 
after completion of treatment, but seldom relapse 
with disease once PCV returns to normal.

608  Blackwell’s Five-Minute Veterinary Consult  
H• Cats have protective immunity against 
M. haemofelis  reinfection for some period of 
time.
SEE ALSO
• Cytauxzoonosis.• Phosphofructokinase Deficiency.
• IMHA = immune-mediated hemolytic anemia.
Barker E. Tasker S. Haemoplasmas: lessons 
learnt from cats. N Z Vet J 2013, 61:184–192.
Messick JB, Harvey JW. Hemotrophic 
mycoplasmosis (haembartonellosis). In: Green CE, Infectious Diseases of the 
Dog and Cat. St. Louis, MO: Elsevier 
Sanders, 2012, pp. 310–319.
Novacco M, Sugiarto S, Willi B, et al. 
Consecutive antibiotic treatment with 
doxycycline and marbofloxacin clears 
bacteremia in Mycoplasma felis -infected cats. 
Vet Microbiol 2018, 217:112–120.
Author  John W. Harvey
Acknowledgment  The author and 
book editors acknowledge the prior 
contribution of Joanne B. Messick.Hemotropic Mycoplasmosis  (continued)

Canine and Feline, Seventh Edition  609
HHepatic Amyloid
  BASICS
OVERVIEW
• Amyloidosis—disorders of diverse etiology 
sharing common feature of deposition of 
extracellular insoluble fibrillar beta-pleated 
proteinaceous matrix with distinctive staining 
properties and fibrillar ultrastructure.
• Amyloid—derived from diverse primary 
proteins, sometimes an acute phase reactant.
• Serum amyloid A (SAA), an acute phase 
protein produced by hepatocytes, is produced 
during inflammation and is associated with 
the most commonly reported generalized 
form of amyloidosis in small animals.
• Amyloid AL, which is a monoclonal 
immunoglobulin G light chain and is 
associated with plasma cell dyscrasia, is not 
commonly reported in small animals and is 
not the form associated with hepatic 
• Amyloid may accumulate as a focal or 
systemic process secondary to inflammatory 
or lymphoproliferative disorders or as a 
familial genetic disorder.
• Liver and kidneys are most commonly 
affected.
• Familial amyloidosis—certain kindreds of 
purebred cats; certain breeds and kindreds of 
dogs; syndromic inflammatory disorders.
• Multiple organs commonly involved; 
clinical signs often reflect renal involvement.
• Liver amyloid accumulation—insidious; 
associated with variable liver enzymes, severe 
hepatomegaly, coagulopathies, liver rupture 
leading to hemoabdomen (cats), or liver failure.
• Dogs—Chinese Shar-Pei, with cyclic 
“shar-pei fever syndrome”; Akita with cyclic 
fever and polyarthropathy; collie with “gray 
collie syndrome”; usually develop renal signs 
first, although some develop hepatic 
• Cats—oriental shorthair, Siamese, Devon 
Rex, domestic shorthair cats; usually <5 years 
of age when first symptomatic (hepatic signs 
and coagulopathies predominate); familial in 
Abyssinians (renal signs predominate). Upper 
respiratory viral infection proposed to trigger 
amyloidosis in Siamese. Cats naturally 
infected with feline immunodeficiency virus 
(FIV) have been described to have systemic 
amyloid deposition, with kidneys, liver, and 
spleen most affected.
SIGNS
• Episodic fever and swollen hocks—shar-pei.
• Episodic polyarthropathy, pain, and signs of 
meningitis—Akita.
• Acute lethargy, cyclic.
• Anorexia and vomiting, episodic.
• Polyuria and polydipsia.Physical Examination Findings
• Pallor.
• Abdominal effusion—hemorrhage or 
ascites.
• Jaundice—unusual.
• Hepatomegaly with amyloid deposition.
• Edema—due to hypoalbuminemia 
secondary to pathologic proteinuria.
• Joint pain—Akita, shar-pei syndromes.
• Nonlocalized pain, meningeal pain, and 
abdominal discomfort—with different 
inflammatory disorders promoting amyloid.
• Familial immunoregulatory disorders.
• Chronic infections—coccidioidomycosis; 
blastomycosis; tick-borne diseases; FIV.
• Cyclic neutropenia—gray collie syndrome.
• Chronic inflammation (e.g., systemic lupus 
erythematosus [SLE]).
  DIAGNOSIS
• Chronic hepatic inflammation.
• Infiltrative hepatic neoplasia.
• Primary or rodenticide-induced 
• SLE.
• Abdominal trauma.
• Immune-mediated or infectious 
polyarthropathy.
• Anemia secondary to hepatic hemorrhage 
or liver lobe rupture or chronic 
• Leukocytosis with a left shift during febrile 
episodes in shar-pei and Akita.
• Normal or high—liver enzymes, total 
bilirubin, and serum bile acids; may be 
normal with severe hepatic amyloid 
• Azotemia with severe renal infiltration—
glomeruli targeted in dogs (proteinuria), 
renal interstitium targeted in cats (azotemia).
• Proteinuria—dogs: glomerular amyloid.
• Dilute urine—renal involvement or failure.
• Feline systemic amyloidosis—involves 
multiple organ systems: thyroid, cardiac, 
renal, intestine, pancreatic, bone marrow, 
lymph nodes, adrenals.
• Coagulation tests—normal to prolonged 
clotting times, hyperfibrinogenemia.
• Synovial fluid—dogs with joint swelling or 
pain: suppurative nonseptic inflammation.
• Cerebrospinal fluid (CSF)—if meningeal pain, increased protein, and suppurative 
• Lyme disease testing—ELISA for C6 
antibody presence in dogs with joint swelling/
pain/fever.
• FIV—cats with hepatic, renal, or respiratory 
symptoms.
IMAGING
• Abdominal radiography—hepatomegaly; 
variable renal size; abdominal effusion.
• Abdominal ultrasonography—
hepatomegaly: hypoechoic parenchyma 
(diffuse amyloid); variable renal size with 
normal or equivocally hypoechoic parenchyma 
(renal amyloid); inconsistent mesenteric 
lymphadenopathy; thickened gut wall 
(amyloid deposition); abdominal effusion.
• Fine-needle aspiration cytology—may 
disclose amorphous fibrillar material.
• Liver or other tissue biopsy.
• Abdominocentesis—hemorrhagic (esp.  
cats) or transudative effusion (diffuse 
hepatopathy).
Gross
Liver—normal to pale color; large, firm to 
friable; hemorrhages (subcapsular hematomas, 
capsular tears) to overt rupture.
• Liver—diffuse acellular amorphous material 
in the space of Disse, associated with hepatic 
cord atrophy; may primarily involve blood 
vessels in portal triads (Abyssinian cats).
• Cats with systemic amyloidosis may have 
amyloid deposited in many organs and 
endocrine tissue.
• Amyloid stains amorphous pink with 
routine hematoxylin and eosin; may stain 
turquoise blue with Masson’s trichrome; 
Congo red staining with bright field: amyloid 
is salmon pink but with polarized light is 
birefringent (beta-pleated sheet structure 
refracts polarized light) and apple green.
  TREATMENT
• Warn client that hepatic amyloidosis is 
difficult to treat; guarded to poor prognosis.
• Dictated by severity of clinical signs.
• No curative treatment; manage underlying 
disease; colchicine as described below may 
reduce organ amyloid deposition.
• Fluids—for dehydration.
• Blood transfusion—for acute blood loss; 
essential in cats with hepatic amyloid-induced 
liver lobe rupture.
• Diet—individually tailored to organ function.
• Liver failure—consider measures  appropriate 
for hepatic encephalopathy as appropriate.
• Pathologic proteinuria—see Nephrotic 
Syndrome.

610  Blackwell’s Five-Minute Veterinary Consult  
H• Surgical intervention—hepatic lobe resection 
as emergency measure for catastrophic bleeding 
from fractured liver lobe in cats; histologic 
features may describe centrilobular necrosis 
due to anemia-induced hypoxia; amyloid may 
be overlooked without special stains.
• Colchicine—dogs: 0.03 mg/kg PO q24h; 
may block amyloid deposition in early 
disease or control deposition in chronic 
disorders in dogs; modulates expression of 
adhesion molecules and chemotactic 
factors; causes microtubule polymerization 
by binding to tubulin blocking cell mitosis 
in cells such as neutrophils. Effects 
attenuate inflammatory response, triggering 
acute phase protein (amyloid precursor) 
production. Monitor CBC for bone 
marrow toxicity; observe patient for enteric 
side effects (vomiting, diarrhea [bloody]), 
beware of toxicity if coadministered with 
p450 blocking drugs (e.g., ketoconazole, 
omeprazole, cimetidine). Use colchicine 
without added probenecid. Limited 
experience in cats.
• Dimethyl sulfoxide (DMSO)—  controversial 
treatment; use medical grade only; dogs: 
80 mg/kg given as no more than a 33% 
solution in sterile water PO three times a 
week; may promote dissolution of amyloid 
fibrils or provide anti-inflammatory or 
anti-amyloid effect. Side effects: garlic odor 
and objectionable taste. Sterile solutions have 
also been prepared and administered SC. In 
humans this treatment given PO daily 
(3–20 g/patient) has benefit in polysystemic 
amyloidosis, but not renal amyloidosis 
associated with renal failure.• Lactulose—dogs: 2.5–15 mL PO q8h; cats: 
2.5–5.0 mL PO q8–12h; for patients with 
suspected hepatic encephalopathy. If oral 
administration is not tolerated this may be 
given as a retention enema.
(NSAIDs)—in dogs (shar-pei fever syndrome) 
to reduce pain and fever if present.
• Vitamin K1—dogs and cats: initially at 
three doses of 0.5–1.5 mg/kg SC/IM. 
Subsequent dosing may be necessary, 
especially in cats. Monitor prothrombin time 
(PT); dosing interval should be determined 
by resolution of prolongation of PT.
• Medications as indicated for concurrent 
renal disease and/or proteinuria if present.
• Colchicine combined with probenecid may 
cause vomiting, as probenecid prolongs 
residence time of colchicine.
• Colchicine toxicity if coadministered with 
p450 cytochrome inhibitor drugs.
• Colchicine may cause/enhance bone 
marrow suppression if administered with 
antineoplastics, immunosuppressive 
medications, chloramphenicol, or 
amphotericin B.
  FOLLOW-UP
• Shar-pei—with hepatic amyloid may 
survive >2 years; most have episodes of fever 
and cholestasis; some resolve clinical signs 
and diminish hepatic amyloid with 
colchicine.
• Akitas with cyclic clinical signs—grave 
• Cats surviving liver hemorrhage eventually 
succumb to renal failure and other 
polysystemic effects of deposited amyloid.  MISCELLANEOUS
SEE ALSO
Amyloidosis
drug.
Amemori S, Iwakiri R, Endo H, et al. Oral 
dimethyl sulfoxide for systemic amyloid 
A amyloidosis complication in chronic 
inflammatory disease: a retrospective 
patient chart review. J Gastroenterol 2006, 
41:444–449.
Beatty JA, Barrs VR, Martin PA. Spontaneous 
hepatic rupture in six cats with systemic 
amyloidosis. J Small Anim Pract 2002, 
43:355–363.
Hoffman HM. Therapy of autoinflammatory 
syndromes. J Allergy Clin Immunol 2009, 
124:1129–1138.
Loevan KO. Hepatic amyloidosis in two 
Chinese Shar Pei dogs. J Am Vet Med Assoc 
1994, 204:1212–1216.
Merlini G, Bellotti V. Molecular mechanisms 
of amyloidosis. N Engl J Med 2003, 
349:583–596.
Author  Kate Holan
Sharon A. Center.Hepatic Amyloid  (continued)

Canine and Feline, Seventh Edition  611
HHepatic Encephalopathy
  BASICS
• Hepatic encephalopathy (HE) defines broad 
spectrum of neurobehavioral signs caused by 
failure of liver to remove endogenous toxins, 
including ammonia, acquired from alimentary 
canal (predominantly from colon) into 
splanchnic portal venous circulation.
• Associated with acute liver failure; porto­
systemic shunting: congenital (portosystemic 
vascular anomaly [PSVA]) or multiple 
acquired portosystemic shunts (APSSs); or 
severe liver injury: critical loss of functional 
hepatic mass or cirrhosis where loss of 
functional mass combines with hepatic 
fibrosis, leading to portal hypertension and 
development of APSS.
• Metabolic/physiologic dysregulations causal 
to HE potentially reversible; pathologic 
changes in neural tissue may become 
permanent in chronic HE.
• Acute brain edema associated with high 
central spinal fluid pressure may lead to lethal 
brain herniation.
• Neurobehavioral and neurocognitive 
abnormalities—largely attributed to 
gut­derived substances (bacterial and protein 
metabolites), with ammonia considered 
predominant toxin.
• Neurologic signs—reflect impact of 
neurotoxic molecules on cortical, basal 
ganglia, pontine, cerebellum, increased 
permeability of blood–brain barrier (BBB); 
astrocyte type II Alzheimer change, microglial 
activation, axonal demyelination, decreased 
cerebellar inhibition.
• Multifactorial process with numerous 
etiopathogenic mechanisms.
• Ammonia—best ­studied toxin with 
neurotoxic impact on astrocytes; high 
ammonia associated with astrocyte swelling 
and brain oxidative stress.
• Complex multifactorial pathophysiology 
contributes to electrophysiologic derange­
ments—energy failure (neuroglycopenia), 
altered cerebral pH (lactate accumulation), 
calcium ion flux, abnormalities involving 
glutamatergic, GABAergic and catechola­
minergic neurotransmission; perturbed aromatic 
amino acid metabolism, increased cerebral 
concentrations of endogenous benzodiazepine ­
like substances and neurosteroids; local 
accumulation of inflammatory cytokines and 
bile acids, altered cerebral blood flow, and 
oxidative injury. Altered BBB permeability 
increases access of toxic factors to brain.
• Nervous—abnormal cerebral function 
predominates; decreased awareness and 
function progress to stereotypic pacing, somnolence, coma, or agitation progresses to 
seizures; aggression and seizures more likely in 
cats with PSVA.
anorexia, or constipation.
urolithiasis involving bladder, renal pelvis; 
may cause urethral obstruction.
GENETICS
• PSVA—see Portosystemic Vascular 
Anomaly, Congenital.
• See Hepatitis, Chronic; Copper Associated 
Hepatopathy.
Uncommon disorder.
Species
PSVA—usually purebred small dogs and 
mixes of these.
• PSVA—usually young animals.
• Acquired liver disease with APSS—any age.
SIGNS
• Neurologic—usually coordinate with meal 
ingestion (esp. high protein, e.g., red meat, 
fish, dogs consuming cat foods); systemic 
infection; dehydration; azotemia; constipation; 
any cause of catabolism; increased heme 
turnover: hemolysis, enteric bleeding, eruption 
of adult teeth in juveniles, blood transfusion; 
certain drugs.
• Temporary resolution of HE signs following 
dietary protein restriction, modification of 
enteric flora or enteric contents (e.g., certain 
oral antibiotics, administration of cathartics 
such as lactulose, or use of cleansing enema), 
± resolution of provocative conditions.
• Prolonged recovery from sedation or 
anesthesia.
• Ammonium biurate obstructive uropathy.
• Episodic neurobehavioral signs or neuro­
cognitive impairment—slow onset and 
• Learning disabilities (difficult to train).
• Lethargy/somnolence may progress to 
coma.
• Anorexia/vomiting.
• Ptyalism—especially cats.
• Polyuria/polydipsia (PU/PD).
• Disorientation—aimless wandering; 
compulsive pacing; head pressing.
• Amaurotic blindness.
• Focal or generalized seizures—neurologic 
signs of lethargy or somnolence as prodrome.
• Signs more frequent in cats—ptyalism, 
seizure, aggression disorientation; ataxic 
stupor.• Signs more frequent in dogs—compulsive 
behavior, e.g., head pressing, circling, aimless 
wandering, vocalizing; GI signs: vomiting; 
diarrhea; PU/PD; signs associated with 
ammonium biurate urolithiasis: hematuria, 
pollakiuria, stranguria, dysuria males > 
females.
• Ascites common in dogs with HE 
secondary to acquired liver disease; variable 
coagulopathies.
• May have distended bladder if obstructive 
uropathy; may pass small dark green uroliths.
• Neurologic signs.
CAUSES
• PSVA—congenital malformations.
• APSS—see Hypertension, Portal; 
Portosystemic Shunting, Acquired.
• See Hepatic Failure, Acute; Hepatotoxins.
• Feeding high ­protein foods to dogs; dogs 
consuming cat foods.
• Enteric bleeding—most common acute 
cause of HE.
• Disorders increasing heme turnover—
enteric bleeding; hemolysis; oral bleeding: 
tooth eruption in juvenile with PSVA; blood 
transfusions: stored blood products may 
contain high concentrations of ammonia, 
incompatible blood transfusions.
• Alkalosis, hypokalemia, hypoglycemia.
• Certain anesthetics (alfaxalone), sedatives 
(benzodiazepines).
• Drugs, e.g., methionine, tetracycline, 
• Catabolism.
• Infections or severe inflammation.
  DIAGNOSIS
• Lead toxicosis.
• Urinary tract infection, urolithiasis.
• Intestinal parasitism.
• Primary GI disease.
• Congenital CNS disease or malformation—
hydrocephalus; storage diseases.
• CNS neoplasia.
• Acute ethylene glycol, xylitol, other 
toxicoses.
• Infectious—rabies; canine distemper; 
neurologic dissemination of toxoplasmosis or 
other.
• Thiamin deficiency.
• Drug intoxications—human recreational 
drugs.

612  Blackwell’s Five-Minute Veterinary Consult  
HCBC/BIOCHEMISTRY/URINALYSIS
CBC
PSVA and APSS—red blood cell microcyto­
sis; variable mild nonregenerative anemia; 
poikilocytosis (cats); target cells (dogs); ± 
jaundiced plasma.
• Variable low blood urea nitrogen and 
creatinine.
• Low cholesterol.
• Liver enzymes—variable depending on 
cause.
• Bilirubin—normal to high depending on 
cause.
• Low concentration—common with PSVA; 
variable with APSS.
• Ammonium urate crystalluria—causing 
hematuria, pyuria, proteinuria; may also cause 
secondary infection; crystalluria imparts 
orange/brown color to urine.
• Blood ammonia—sensitive but unreliable 
indicator of HE; fasting hyperammonemia 
unreliably associated with HE; lability of blood 
ammonia makes ammonia determinations less 
reliable than total serum bile acids (TSBA); 
ammonia tolerance testing—most reliable 
method of demonstrating ammonia intoler ­
ance (administer NH4Cl PO or per rectum) 
but caution : may induce HE.
• TSBA—confirms hepatic insufficiency or 
shunting associated with HE; hepatobiliary 
jaundice renders TSBA testing superfluous.
• Coagulation tests—variable depending on 
• Protein C—low activity in dogs with 
substantial shunting, liver failure, protein ­
losing enteropathy, disseminated intravascular 
• Abdominal effusion—effusions pure or 
modified transudates.
IMAGING
See Portosystemic Vascular Anomaly, 
Congenital; Portosystemic Shunting, 
Acquired.
• Hepatic aspiration—cannot differentiate 
disorders causing portosystemic shunting.
• Liver biopsy—open surgical wedge biopsy 
or laparoscopic sampling; essential to collect 
tissue from several liver lobes.
• T ru­Cut® needle biopsy—may inadequately 
sample tissue.
• Gross—liver appearance reflects underlying 
disorder; rare brain herniation in acute HE.
• Microscopic—liver lesions define causal 
hepatic disorder; CNS lesions: may include polymicrocavitation and Alzheimer type II 
astrocyte changes; inconsistent in dogs and cats.
  TREATMENT
• See Portosystemic Vascular Anomaly, 
• Avoid risk factors.
• T reatment depends on underlying 
condition(s); essential to eliminate factors 
provoking HE.
• Improve dietary protein tolerance by 
concurrent oral or rectal (enema) treatments 
(see Medications) and altering protein type 
and quantity (see Diet).
• If hepatic coma—discontinue oral 
medications; ensure euglycemia; provide fluid, 
electrolyte, and water ­soluble vitamin support.
• Fluids—balanced crystalloids; avoid lactate 
if fulminant hepatic failure, if hypoglycemic 
supplement fluids with 2.5–5.0% dextrose; 
provide 20–30 mEq/L potassium chloride 
(not to exceed 0.5 mEq/kg/h) titrated to 
need; sodium ­restricted fluids used in patients 
with ascites with APSS (esp. cirrhosis) and 
patients with marked hypoalbuminemia.
• B­soluble vitamins supplemented in fluids 
(2 mL/L); ensure adequate B12.
ACTIVITY
• Keep patient warm, inactive, hydrated, 
euglycemic.
• Protect animal from environmental injury 
secondary to propulsive or aimless pacing, 
obtundation, amaurosis, generalized seizures.
DIET
• Adequate calories—avoid catabolism; 
important to maintain muscle mass.
• Dietary protein modification and 
restriction—cornerstone of medical 
management; use commercially formulated 
liver diets or diets for moderate renal 
insufficiency. Dog: use dairy and soy protein 
sources with initial 2.2–2.5 g protein/kg 
bodyweight per day allowance. Cat: pure 
carnivores must have meat ­derived protein 
restricted to ~3.5 g protein/kg bodyweight 
per day.
• Dogs: after initial observed response to 
restricted protein allowance (1–2 weeks) 
gradually titrate allowance upward (0.25 g 
protein/kg bodyweight per day for 5–10 ­day 
observational increments) using dairy quality 
protein (e.g., shredded cheddar or mixed 
cheeses, often effective); increase up to 1.5 g 
protein /kg bodyweight per day depending on 
individual tolerance (no signs of HE, no 
ammonium biurate crystalluria).
• Good ­quality vitamin supplements.• Ensure thiamin repletion—50–100 mg 
daily for 3 days in cats and dogs, with 
water ­soluble vitamins added in fluids; follow 
with dietary supplementation; caution : 
anaphylactoid reactions may occur with 
injectable (IM/SC) thiamin.
• S-adenosylmethionine—20 mg/kg PO/day 
on empty stomach.
• Partial parenteral nutrition— only for 
short ­term inappetence.
• Total parenteral nutrition considered if >5 
days inappetence and enteral route 
unavailable.
• No benefit shown for specific 
supplementation of oral branched ­chain 
amino acids.
• No need to restrict fat.
• HE—usually episodic; relapse risk exists if 
underlying cause cannot be eliminated.
• T rain owner to administer enemas to abate 
acute ­onset HE and judiciously adjust 
medications used to control ammonia 
formation and absorption PRN.
• APSS—see Portosystemic Shunting, 
Acquired.
• PSVA—medically treat HE before  
anesthesia and surgery.
• APSS—do not ligate this vasculature.
• T reatment goals include increasing dietary 
protein tolerance; altering enteric environment 
and microbiome to modify generation of 
encephalogenic toxins (e.g., endotoxin and 
ammonia); reduce bioavailability or colonic 
dwell time of substances provoking HE.
• Antibiotics—first choice: systemic 
metronidazole (7.5 mg/kg q12h) or 
amoxicillin (esp. cats, 12.5–25 mg/kg PO 
q8–12h); caution  if using neomycin (10–
22 mg/kg PO q12h) chronically as enteric 
absorption may cause renal and otic toxicity.
• Local instillation of antimicrobials used in 
retention enemas—same dosages as oral but do 
not administer by both oral and rectal routes.
• In humans, rifaximin is as effective as single 
agent or combined lactulose and neomycin in 
management of HE and has favorable safety 
and tolerability profile; is expensive; no data 
regarding utility for management of HE in 
animals; suggested dose in dogs 5 mg/kg PO 
q24h or q12h.
• Nonabsorbable ­fermentable carbohydrates—
lactulose, lactitol, or lactose in milk products if 
patient is lactase deficient; lactulose most 
commonly used: start at 0.5 mL/kg q8–12h Hepatic Encephalopathy  (continued)

Canine and Feline, Seventh Edition  613
Hand titrate up to therapeutic goal of 2 or 3 soft 
stools/day; may also administer as enema for 
acute HE or patients in coma after cleansing 
enemas remove debris; note: concurrent use of 
neomycin may suppress bacterial fermentation 
of lactulose thereby diminishing its benefit.
• Probiotics combined with nonabsorbable ­
fermented carbohydrates may be advantageous 
for altering gut flora and provoking cathartic 
effect.
• Enemas— cleansing enemas  (warmed 
polyionic fluids) mechanically cleanse the colon 
(10–15 mL/kg, until clear return); retention 
enemas  deliver fermentable substrates, 
antimicrobials, or solution directly altering 
colonic pH: diluted lactulose, lactitol, or lactose 
(1 : 2 in water); antimicrobials mixed with 
water: metronidazole or neomycin but do not 
exceed PO dose, do not dose PO and rectally; 
diluted betadine (1 : 10 in water, rinse well in 
15 min ); diluted vinegar (1 : 10 in water) 
modifies colonic pH, alters colonic flora.
• Zinc supplementation—two urea cycle 
enzymes require zinc and portosystemic 
shunting may deplete body zinc reserves 
(shown in humans); measure baseline plasma 
zinc (dose 1–3 mg/kg elemental zinc PO 
using zinc acetate) then titrate dose using 
sequential plasma zinc measurements to 
avoid  >800 μg/dL (causes hemolysis), but 
document an increase in baseline plasma zinc 
concentration inferring positive zinc balance; 
note: plasma zinc does not reflect liver zinc 
• Cerebral edema—complicates acute HE; 
head­up posture (15–20° incline); mannitol 
(1 g/kg diluted in saline, over 30 min); nasal 
oxygen; N­acetylcysteine (140 mg/kg IV 
diluted 1 : 2 in saline given through 
nonpyrogenic filter unless sterile IV form 
used, then 70 mg/kg q8h); glucocorticoids 
controversial, may promote enteric bleeding 
but some evidence supports reduced astrocyte 
swelling.
• Salvage therapies for intractable HE 
(experimental)—l ­ornithine ­l­aspartate 
(humans, rats: 180–300 mg/kg/day divided 
into three doses); l ­carnitine (100 mg/kg PO/
IV) may attenuate HE ­associated 
hyperammonemia.
• If epileptic seizure activity—Keppra® 
(levetiracetam; dose 20–60 mg/kg IV given 
1 : 1 dilution over 15 min) is preferred 
anticonvulsant; secondary anticonvulsants 
include zonisamide (caution: rare idiopathic 
hepatotoxicity) or KBr (complicates fluid therapy) as preferred anticonvulsants to 
phenobarbital; avoid benzodiazepines in HE.
• Avoid drugs metabolized by the liver or 
rapidly removed by first ­pass extraction—or if 
used, judiciously reduce dose.
• Avoid alfaxalone.
• Avoid benzodiazepines.
• Consider altered drug pharmacokinetics—
reduced first ­pass extraction due to porto­
systemic shunting; reduced protein binding if 
hypoalbuminemia, and compromised hepatic 
• Use anesthetics, sedatives, tranquilizers, 
potassium ­wasting diuretics, analgesics, highly 
protein ­bound drugs (if hypoalbuminemic) 
cautiously; reduce dose.
• If possible, avoid drugs predominantly 
reliant on hepatic metabolism, biotransform­
ation, and excretion in patients with acquired 
chronic liver disease associated with APSS vs. 
those with PSVA or ductal plate malformation ­
associated APSS where metabolic or synthetic 
failure less likely.
• Avoid drugs or reduce dose if highly reliant 
on first ­pass hepatic extraction if PSVA or 
APSS.
Drugs that influence p450 cytochrome 
hepatic metabolism, e.g., cimetidine, 
chloramphenicol, barbiturates, ketoconazole, 
may provoke adverse drug interactions.
  FOLLOW-UP
• Reevaluate patient at ­home behavior and 
cognitive function, body condition, muscle 
mass, and weight; owner should record diary 
of progress and video abnormal behaviors.
• Monitor albumin and glucose.
• Adjust nutrition to optimize protein 
allowance and avoid sarcopenia.
• Monitor electrolytes—especially potassium 
if PU/PD or if diuretics prescribed.
Avoid provocative conditions—dehydration, 
azotemia, constipation, endoparasitism, 
enteric or oral bleeding, infusion of stored 
blood, hemolysis, meal ­related ammonia 
challenge, urinary tract infections, 
hypokalemia, hypomagnesemia, alkalemia; and manage systemic infection or 
Permanent neurologic damage may develop 
in chronic recurrent HE but uncommon; 
most often encountered in PSVA with acute 
severe HE.
• Depends on underlying disorder.
• Acute or chronic hepatic failure—may 
be fully or partially reversible, or patient 
may die.
PSVA—surgical outcome may be good in 
young and old patients.
SYNONYMS
• Hepatic coma.
• Portosystemic encephalopathy.
SEE ALSO
• Arteriovenous Malformation of the Liver.
• BBB = blood–brain barrier.
Hajihambi A, Arias N, Sheikh M, et al. 
Hepatic encephalopathy: a critical current 
review. Hepatol Int 2018, 12 (Suppl 
1):S135–S147.
Lidbury JA, Cook AK, Steiner JM. Hepatic 
encephalopathy in dogs and cats. J Vet 
Emerg Crit Care 2016, 26:471–487.
Editor  Kate Holan
available online(continued)  Hepatic Encephalopathy

614  Blackwell’s Five-Minute Veterinary Consult  
HHepatic Failure, Acute
  BASICS
• Severe acute hepatic injury incapacitating 
ability to meet synthetic, metabolic, 
detoxification needs.
• Sudden loss of >75% of functional hepatic 
mass due to acute, massive hepatic necrosis.
• May lead to catastrophic multiorgan 
dysfunction/failure in previously healthy 
individual; may rapidly progress to death.
• Necrosis—secondary to insufficient 
perfusion, hypoxia, hepatotoxins (drugs, 
other xenobiotics, toxins), heat excess, 
• Severity of hepatic dysfunction depends on 
insult type and lobular (zonal) distribution.
• Reduced perfusion or hypoxia usually affects 
zone 3 (pericentral or centrilobular region).
• Ingested toxins—affect zone where toxin 
metabolized or toxic product formed, or 
where specific organelle tropism or propensity 
for oxidative injury (copper accumulation 
increases zone 3 vulnerability).
• Panlobular hepatic necrosis leading to acute 
liver failure uncommon; e.g., idiosyncratic 
drug toxicity: dogs—zonisamide, phenobarbital, 
primidone, diphenylhydantoin, nonsteroidal 
anti-inflammatory drugs (NSAIDs, e.g., 
carprofen), xylitol; cats—diazepam; dogs or 
cats—sulfa-antibiotics; primary toxins: dogs 
and cats—primary copper accumulation, 
acetaminophen; dogs—zonisamide, xylitol, 
cycad (sago palm), cheese tree ( Glochidion 
ferdinandi ) roots, blue-green algae, Amanita  
mushrooms, aflatoxin; infectious disease: 
dogs—leptospirosis, infectious canine 
• Accompanied by enzyme leakage and 
markers of impaired liver function, 
hyperbilirubinemia, acute-onset splanchnic 
hypertension due to sinusoidal or 
centrilobular collapse.
• Lethal organ failure associated with 
coagulopathy, enteric hemorrhage, acute-
onset hepatic encephalopathy (HE).
• Hepatic failure—associates with myriad 
metabolic derangements: altered glucose 
homeostasis, protein synthesis (albumin, 
transport proteins, procoagulants, 
anticoagulants), detoxification capabilities.
• Hepatobiliary—hepatocellular necrosis; 
hepatic failure, jaundice.
• Nervous—HE; cerebral edema.
• Gastrointestinal (GI)—vomiting; diarrhea; 
melena; hematochezia due to acute 
splanchnic hypertension ± coagulopathy.
• Hemic/lymphatic/immune—pro- and 
anticoagulant factor imbalances; disseminated 
intravascular coagulation (DIC).• Renal/urologic—renal tubule damage from 
certain toxins or physiologic vasoconstriction; 
tubular injury: copper associated hepatopathy, 
leptospirosis, xylitol toxicity, NSAID toxicity.
• Hyperdynamic circulatory status—low 
systemic and pulmonary vascular resistance, 
increased cardiac output and metabolic rate, 
systemic hypotension; associates with 
endotoxemia, TNF- α, dehydration, and 
splanchnic hypertension.
Variable depending on preexistent liver disease: 
hepatocellular copper accumulation, chronic 
immune-mediated hepatitis, cholangitis.
Species
More common in dog than cat.
Breeds with apparent predisposition to 
chronic hepatitis and copper associated 
hepatopathy (e.g., Labrador retriever, 
Doberman pinscher, Bedlington terrier) may 
have higher risk, e.g., Labrador retrievers and 
NSAID toxicity enhanced by copper 
associated hepatopathy.
SIGNS
• Acute-onset nonspecific clinical signs; 
lethargy, inappetence, GI disturbances 
(vomiting, small intestinal diarrhea may be 
bloody), polyuria/polydipsia (PU/PD).
• Tender hepatomegaly.
• Bleeding tendencies.
• HE.
CAUSES
Drugs
• See Hepatotoxins.
• Drug-related toxicities intrinsic  (direct) or 
idiosyncratic  (unpredictable, unrelated to 
dose) consequent to immune-mediated 
hypersensitivity or metabolic injury.
Thermal Injury
• Whole-body hyperthermia cancer 
Hepatic Hypoxia
• Thromboembolic disease, shock, DIC.
• Acute circulatory failure from any cause.
• Acute centrilobular necrosis (zone 3).
• Administration of potentially hepatotoxic 
substance or drug.
• Exposure to environmental toxins (e.g., 
Amanita  mushroom, foodborne aflatoxin, cycad, 
cheese tree roots, blue-green algae), artificial 
sweetener—xylitol (gum, candy): dogs).
• Enzyme inducers (e.g., phenobarbital)—may 
increase risk for toxicities by enhancing 
xenobiotic toxin formation, e.g., acetaminophen 
toxicity greatly enhanced by phenobarbital.• Indiscriminate substance ingestion—
puppies; polyphagic animals.
  DIAGNOSIS
• Severe acute pancreatitis or gastroenteritis—
differentiated via laboratory tests and 
imaging.
• Acutely decompensated chronic liver 
disease—distinguished by review of medical 
records, blood tests, abdominal US, liver 
biopsy.
• Anemia and panhypoproteinemia—bleeding, 
marrow toxicity, direct enteric toxicity.
• Thrombocytopenia—bleeding, DIC, portal 
• Liver enzyme activity—high acute alanine 
aminotransferase, and aspartate aminotransferase; 
smaller increases in alkaline phosphatase and 
γ-glutamyltransferase.
• Hypoglycemia—grave prognosis (esp. cats).
• Hypocholesterolemia—impaired synthesis 
or enteric loss with hemorrhage.
• Normal to low blood urea nitrogen 
concentration—reduced urea cycle function, 
PU/PD.
• Hyperbilirubinemia—initially absent.
• Bilirubinuria may precede hyperbilirubinemia—  
always abnormal in cats.
• Ammonium urate crystalluria signifies 
hyperammonemia, hepatic insufficiency, or 
• Acquired Fanconi syndrome—granular 
casts and renal glucosuria indicate proximal 
tubule injury (e.g., carprofen, copper, 
leptospirosis, other toxicities esp. in dogs).
• Total serum bile acids (TSBA)—high values 
indicate hepatic dysfunction, cholestasis, or 
• Plasma ammonia concentration—high 
values coincide with high TSBA, confirm 
hepatic insufficiency; hyperammonemia 
inconsistent but reflected by ammonium 
biurate crystalluria; hyperammonemia may 
reflect concurrent myonecrosis.
• Coagulation tests—coagulation factor 
deficiencies, platelet dysfunction, low 
fibrinogen, low antithrombin or protein C 
activity, and DIC suggest severe liver failure, 
decompensated DIC, or enteric losses with 
IMAGING
• Abdominal radiography—may identify 
normal to slightly enlarged liver ± effusion.
• Abdominal US—may disclose nonhepatic 
disorders (e.g., pancreatitis), altered 
circulation (ratio hepatic vein : portal vein), 
altered liver echogenicity or surface contour 
reflecting chronic injury (e.g., remodeling

Canine and Feline, Seventh Edition  615
Himplicated by heterogeneous liver texture, 
nodularity, or hepatofugal portal blood flow); 
rule out biliary obstruction as source of 
hyperbilirubinemia.
• Brain MRI—may disclose early cerebral 
edema (not commonly done).
• Liver biopsy—confirms necrosis, 
characterizes lesion zonal distribution.
• Fine-needle liver aspirate may identify 
hepatocellular degeneration, copper 
accumulation, dysplastic hepatocytes observed 
with cycad or aflatoxin ingestion; canalicular 
cholestasis; many toxins lead to microvesicular 
hepatocellular lipid vacuolation.
• Gross—slightly enlarged, mottled liver.
• Microscopic—confirms necrosis; zonal 
involvement; may assist in determining 
underlying cause: hypoxia leading to zone 3 
necrosis; certain toxins cause zone 1 or 3 
necrosis; reticulin staining confirms zonal 
involvement, retention, or loss of reticulin 
substructure that orchestrates organized 
regeneration.
  TREATMENT
Inpatient—intensive care needed.
• Caution : delay inserting central catheters 
until bleeding diatheses controlled with 
vitamin K1, fresh frozen plasma (FFP), or 
fresh whole blood; no advantage to 
prophylactic FFP administration as may 
contribute to onset of HE and cerebral edema.
• Fluids—non–lactate-containing; initially at 
resuscitation rate; monitor peripheral BP , 
pulse oximetry; mixed acid-base disturbances 
common.
• Colloid replacement—when low oncotic 
pressure from bleeding and protein loss; 
plasma always preferred; synthetic colloids 
second line; avoid dextran 70 and hetastarch 
(may promote bleeding) and human albumin 
(may induce fatal acute allergic reaction).
• Potassium, phosphate, glucose—supplement 
as appropriate; low phosphate, potassium, 
glucose aggravate HE and other clinical signs, 
complicating critical supportive care.
• Fluid regimen—adjust for maintenance needs 
after achieving euvolemia; typically provide ⅓ 
normal maintenance rate with polyionic 
crystalloids if concurrently giving slow CRI of 
synthetic colloid; avoid colloids if possible as 
leak from microvasculature (exacerbated with 
some toxicities that affect endothelium) and 
disturb signaling that triggers albumin and 
transporter protein synthesis.
• Supplemental oxygen—if pulse oximetry 
≤94% saturation.• If suspect cerebral edema—use 30° head-up 
elevation, consider mannitol, other interventions.
• Predisposition to infection from enteric 
bacterial translocation—cover with broad-
spectrum antimicrobials; patient may not 
manifest fever or leukocytosis with infection; 
sepsis/systemic inflammatory response 
syndrome—major risks for cerebral edema.
• Early administration of N-acetylcysteine 
may improve microvascular perfusion, tissue 
oxygenation, and mitigate oxidative damage 
ACTIVITY
Restricted activity—conserves energy and 
metabolites for healing and regeneration.
DIET
• Intractable vomiting—withhold PO food 
until controlled; antiemetics (see below).
• When enteric nutrition contraindicated 
(somnolent patient) use partial or total 
parenteral nutrition (TPN) until enteral 
feeding route established; <5 days advised.
• If enteric nutrition chronically compromised, 
establish TPN feeding catheter; use TPN 
formula with normal nitrogen content unless 
HE; branched-chain amino acids still 
controversial.
• Enteral feeding—small-volume, frequent 
meals; optimize digestion and assimilation, 
minimize enteric toxin formation contributing 
to HE.
• Diet composition—use normal protein 
(nitrogen) content in tolerant patients; moderate 
protein restriction if HE (2.5 g protein/kg 
bodyweight) but strive to maintain positive 
nitrogen balance for hepatic regeneration.
• Supplemental vitamins essential—water-
soluble (twice normal); vitamin K1 (0.5–
1.5 mg/kg SC/IM, three doses at 12h 
intervals, then once to twice weekly); vitamin 
E (10 IU/kg PO or by injection q24h).
• Pro-/prebiotic yogurt—may protect against 
enteric bacterial translocation; tolerated dairy 
protein source if HE; controversial.
• Acute hepatic failure is serious condition.
• Some patients succumb despite optimal 
• Cause of panlobular injury (e.g., exposure 
to drug or toxin) should be investigated but 
may remain unconfirmed.
Drugs for Vomiting
• Metoclopramide—1–2 mg/kg/day CRI for 
intermittent mild vomiting; contraindicated if 
spironolactone used for ascites mobilization.
• Ondansetron—0.5–1.0 mg/kg IV q12h.
• Maropitant—1.0 mg/kg IV/SC q24h (some suggest decreasing dose by 50% in patients 
with hepatic dysfunction due to hepatic 
metabolism).
• Omeprazole (0.5–1.0 mg/kg PO q12–24h) 
or pantoprazole (0.7–1.0 mg/kg IV q12h) 
may induce P450 cytochrome–associated 
drug interactions; 24–48h delay in onset of 
action; preferred over H2 blockers for gastric 
• Histamine H2 blocker—famotidine 
(0.5–1.0 mg/kg IM/SC q12–24h) if enteric 
bleeding; reserve cimetidine (0.5 mg/kg q8–12h) 
for purposeful P450 cytochrome inhibition.
• Chlorpromazine—0.5 mg/kg SC/IM/
rectally q8–24h for severe vomiting; ensure 
volume expansion first as causes alpha 
blockade vasodilation.
Drugs for HE
• Lactulose—0.5–2.0 mL/kg PO q8h or 
rectally if PO hazardous; goal is soft feces.
• Probiotic yogurt (see above).
• Metronidazole—7.5 mg/kg PO q12h or 
rectally if PO hazardous.
• Ampicillin/amoxicillin (esp. cats) —12.5–
25 mg/kg IV/PO q8–12h.
• Rifaximin—5–10 mg/kg PO or rectally q12h 
(nonabsorbed antibiotic alters enteric flora).
• Neomycin—22 mg/kg PO or rectally q12h; 
caution : may be ototoxic and renal toxic if 
increased absorption with reduced gut integrity.
Treatment of Cerebral Edema 
Associated with HE
• Mannitol—1 g/kg over 10–20 min, filtered; 
if brisk diuresis does not occur (~1h), check 
for excessive volume expansion (plasma 
osmolality, BP) and renal function.
• Furosemide—0.5–1.0 mg/kg IV q8–24h 
increases free water excretion and reduces 
cerebrospinal fluid (CSF) production; 
monitor hydration and serum potassium; 
avoid dehydration and hypokalemia that 
provoke or worsen HE.
• Vasopressin V2 antagonists (aquaretics) may 
assist with management of diuretic resistant 
ascites; tolvaptan successful in dogs with 
experimentally induced (rapid pacing) 
congestive heart failure (see Hypertension, 
Portal).
Drugs for Coagulopathy
Fresh whole blood or FFP—if clinically 
significant bleeding.
Free Radical Scavengers 
and Antioxidants
• For ongoing damage (membrane injury), 
reperfusion injury, and hypoxia.
• Vitamin E—10 IU/kg PO q24h.
• N-acetylcysteine—140 mg/kg IV/PO 
loading dose; IV use 10% solution diluted 
1 : 2 in saline, administer via 0.25  μm 
nonpyrogenic filter; follow with 70 mg/kg 
q6–12h.
• S-adenosylmethionine as glutathione (GSH) 
donor, use proven bioavailable product— (continued)  Hepatic Failure, Acute

616  Blackwell’s Five-Minute Veterinary Consult  
H20 mg/kg PO q24h on empty stomach; 
multiple benefits: essential intermediary 
metabolites, GSH synthesis, promotes liver 
regeneration, antifibrotic, anti-inflammatory.
• Silybin (milk thistle), efficacy reported 
for Amanita  toxicity and certain other toxins; 
use complexed with polyunsaturated 
 phosphatidylcholine, 2–5 mg/kg PO q24h.
• Ursodeoxycholic acid—if chronic liver 
injury or high bile acids persist, 10–15 mg/kg 
PO q24h or divided q12h, best absorbed with 
food.
Blocking Enterohepatic Circulation
Cholestyramine—30–40 mg/kg mixed with 
water PO q24h; bile acid–binding resin that 
can absorb certain toxins in alimentary canal 
that undergo enterohepatic circulation, 
diminishing systemic availability, e.g., sago 
palm (cycad toxin).
• Ideally avoid drugs biotransformed 
primarily in liver, altering liver perfusion, or 
metabolizing enzyme activity; may be difficult 
as many drugs metabolized in hepatic 
pathways or eliminated in bile.
• Vitamin C—100–500 mg q24h, avoid  if 
high liver iron or copper concentrations; 
ascorbate may augment transition metal–
associated oxidative injury; no substantiation 
for vitamin C administration in liver failure.
Administration of stored whole blood or 
packed red blood cells may precipitate or 
exacerbate HE in dogs with hepatic failure 
because of spontaneously generated ammonia 
during storage.
Compromised hepatic metabolism.
Case-based considerations.
  FOLLOW-UP
• Temperature, pulse, respiration, mental 
status—q1–2h until stable.
• Maintain vigilance for infection, especially 
catheter-induced.• Bodyweight—twice daily guides fluid 
therapy; bodyweight and condition used to 
assess nitrogen and energy allowances.
• Acid-base, electrolyte balances (especially 
potassium and phosphate), glucose—q12–
24h for first 72h.
• Sequential measurements of liver enzymes, 
bilirubin, cholesterol, fibrinogen q2–3 days 
provide evidence of recovery.
• Vaccinate dogs against infectious canine 
hepatitis virus.
• Avoid indiscriminate ingestion of 
hepatotoxins and environmental exposure.
• Consider drugs as potential toxins.
• Uncontrolled GI bleeding and DIC.
• HE, cerebral edema, brain herniation.
• Chronic hepatic insufficiency, cirrhosis, 
fibrosis from postnecrotic scarring.
• Death.
Prognosis—depends on extent of liver injury, 
etiopathogenesis, supportive nursing care.
• Sepsis/endotoxemia/shock.
• Bleeding diathesis; severe enteric 
hemorrhage; DIC.
• HE.
• Toxins (?).
SYNONYMS
• Acute hepatic necrosis.
SEE ALSO
• Ascites.
• Hepatitis, Infectious (Viral) Canine.
• Icterus.ABBREVIATIONS
drug.
• PU/PD = polyuria, polydipsia.
• TPN = total parenteral nutrition.
Center SA. Acute hepatic injury: hepatic 
necrosis and fulminant hepatic failure. In: 
Guilford GW, Center SA, Strombeck DR, 
et al. Small Animal Gastroenterology. 
Philadelphia, PA: Saunders, 1996, pp. 
654–704.
J Am Vet Med Assoc 1996, 209:618–625.
Dunayer EK, Gwaltney-Brant SM. Acute 
hepatic failure and coagulopathy associated 
with xylitol ingestion in eight dogs. J Am 
Vet Med Assoc 2006, 229:1113–1117.
Hughes D, King LG. The diagnosis and 
management of acute liver failure in dogs 
Pract 1995, 25:437–460.
MacPhail CM, Lappin MR, Meyer DJ, et al. 
Hepatocellular toxicosis associated with 
administration of carprofen in 21 dogs. J 
Am Vet Med Assoc 1998, 
212(12):1895–1901.
Miller ML, Center SA, Randolph JF , et al. 
Apparent acute idiosyncratic hepatic 
necrosis associated with zonisamide 
administration in a dog. J Vet Intern Med 
2011, 25:1156–1160.
Authors  Linda K. Okonkowski and Kate 
Holan
Sharon A. Center
available onlineHepatic Failure, Acute  (continued)

Canine and Feline, Seventh Edition  617
HHepatic Lipidosis
  BASICS
• Feline hepatic lipidosis (HL)—lipid 
vacuolation distends the cytosolic compartment 
in >80% of hepatocytes.
• Untreated—leads to progressive metabolic 
dysregulation, hepatic failure, and death.
• Develops secondary to a primary disease or 
condition causing anorexia or catabolism; 
idiopathic HL is uncommon: a cause is 
usually discoverable.
• Cats have a unique propensity to 
accumulate triglyceride-filled hepatocellular 
vacuoles.
• Causal factors—negative energy and 
protein balance with increased peripheral fat 
mobilization.
• Cytosolic triglyceride vacuoles cause severe 
cholestasis and jaundice via canalicular 
compression and associated hepatic organelle 
• Hepatic failure—with rare evidence of 
hepatic encephalopathy (HE).
• Gastrointestinal—anorexia; vomiting.
• Musculoskeletal—peripheral muscle 
wasting (sarcopenia) and fat mobilization.
• Nervous—HE, ptyalism, moribund status.
• Hemic/lymphatic/immune—abnormal red 
blood cell (RBC) shapes (poikilocytes), Heinz 
body hemolysis.
• Renal/urologic—potassium wasting; renal 
tubule triglyceride accumulation.
Most common severe hepatopathy in North 
America causing jaundice in pet cats.
Worldwide
Species
Cats, rarely dogs (toy-breed failure-to-thrive 
puppies), juveniles with lysosomal or 
glycogen storage disease; may develop in 
small-breed puppies with portosystemic 
vascular anomaly (PSVA).
N/A
Middle-aged adult cats—median age 8 
(range: 1–16 years).
N/A
SIGNS
• Anorexia or hyporexia, weight loss, sarcopenia.
• Vomiting, diarrhea or constipation, jaundice.• Lethargy, with gradual onset of weakness 
progressing to collapse.
• Neck ventriflexion—weakness, electrolyte 
depletions (potassium, phosphate), thiamine 
• Underlying disease or illness causing 
hyporexia/anorexia → hepatic lipidosis.
• Weakness—neck ventriflexion, recumbency.
• Collapse ←→ obtunded (signs of HE).
• Others, depending on underlying primary 
disease.
CAUSES
“Idiopathic” Hepatic Lipidosis
Idiopathic = uncommon; antecedent health 
problems discoverable in >85% of cases 
causing anorexia or malassimilation; 
remainder have food deprivation often 
attributable to adverse social interactions, 
environmental cause.
Secondary Hepatic Lipidosis
• Primary liver disease—PSVA; cholangitis/
cholangiohepatitis syndrome (CCHS); 
cholelithiasis; neoplasia.
• Gastrointestinal—obstruction; neoplasia; 
inflammatory bowel disease (IBD); 
• Urogenital disease—renal failure, chronic 
interstitial nephritis (CIN), lower urinary 
tract syndromes.
• Neurologic conditions—cannot eat.
• Infectious diseases—toxoplasmosis; feline 
infectious peritonitis (FIP); feline 
immunodeficiency virus (FIV)– or feline 
leukemia virus (FeLV)–related disorders.
• Vitamin B12 deficiency and deficiency of 
other water-soluble vitamins may predispose 
cats to HL as a result of disrupted metabolism 
as one factor.
• Many other systemic conditions or toxins 
can provoke anorexia and lead to HL.
• Rapid weight loss protocols or change to 
restricted-calorie diet the cat refuses to eat.
• Obesity.
• Anorexia, negative nitrogen balance.
• Catabolism or rapid weight loss.
• Water-soluble vitamin deficiency.
  DIAGNOSIS
• Primary liver disease—CCHS, 
cholelithiasis, EHBDO, or neoplasia (esp. lymphosarcoma) differentiated by abdominal 
US, liver aspiration, and liver biopsy.
• PSVA—diagnosis by US or colorectal 
scintigraphy, lab testing.
• Hepatic toxoplasmosis or FIP—liver biopsy, 
serology, immunohistochemistry.
• Pancreatitis—differentiated by US, serum 
tests, pancreatic aspiration cytology, gross 
inspection, biopsy.
• Gastrointestinal disease—IBD differentiated 
by bowel biopsies; obstruction differentiated 
by abdominal survey or contrast radiography 
and US.
• Toxicities—suspected based on history 
(e.g., oral diazepam, acetaminophen, 
methimazole).
• Hyperthyroidism—serum thyroid panel, 
absence of jaundice.
• Hematology—poikilocytes common; 
nonregenerative anemia; hemolytic 
anemia (severe hypophosphatemia or 
Heinz bodies).
• Biochemistry—hyperbilirubinemia; high 
alkaline phosphatase (ALP), alanine 
aminotransferase (ALT), ± aspartate 
aminotransferase (AST) activity; normal or 
mild increase in 𝛾-glutamyltransferase (GGT) 
if no primary necro-inflammatory ductal 
disorder (i.e., biliary, pancreatic); low blood 
urea nitrogen (BUN); normal creatinine; 
variable glucose (hypoglycemia rare); variable 
cholesterol, albumin, globulins; hypokalemia; 
hypophosphatemia, increased ketones 
(beta-hydroxybutyrate); lactic acidosis.
• Urinalysis—bilirubinuria, lipiduria, and 
unconcentrated urine common.
• Prolonged coagulation times—prothrombin 
time (APTT), activated clotting time (ACT); 
fibrinogen usually normal.
• Hyperammonemia—uncommon.
• Serum bile acids—high before 
hyperbilirubinemic; redundant test if 
hepatobiliary jaundice.
• B12 deficiency.
IMAGING
Survey Abdominal Radiography
• May note features of underlying disorder.
• Diffuse hyperechoic hepatic parenchyma, 
hepatomegaly.
• Look for primary disease causing HL.
• Fine-needle liver aspiration cytol-
ogy— >80% hepatocytes display severe 
cytosolic lipid vacuolation; biopsy rarely 
needed to confirm HL.
• Definitive diagnosis HL—based on history, 
clinical features, high ALP , diffuse hyperechoic 
hepatic parenchyma, severe hepatocyte lipid

618  Blackwell’s Five-Minute Veterinary Consult  
Hvacuolation on aspiration cytology; however, 
cannot rule out primary hepatic disorders (e.g., 
CCHS, EHBDO, PSVA) with these tests.
• Liver biopsy—definitive diagnosis of 
underlying “primary” liver disorders; done 
only if poor response to therapy or high GGT ; 
caution : stabilize cat before anesthesia and 
liver biopsy.
• Vitamin K1 (0.5–1.5 mg/kg SC/IM) three 
doses at 12h intervals, before  aspiration 
sampling, liver biopsy, jugular vein 
catheterization, cystocentesis, or feeding 
appliance insertion.
• Gross—diffuse hepatomegaly, smooth 
surface, friable greasy consistency, yellow/pale 
color with reticulated appearance; sample 
floats in formalin.
• Microscopic—diffuse, severe hepatocellular 
lipid vacuolation; large (macrovesicular) or 
small (microvesicular) vacuolation; type of 
vacuolation lacks prognostic value.
  TREATMENT
• Inpatient—recumbent cats or those with 
neck ventriflexion and anorectic.
• Discharge for home care—see Patient 
Monitoring.
• Frequent reevaluations imperative.
• Outpatient—reduces stress and thereby 
facilitates recovery in some cats.
• Balanced polyionic fluids— avoid  lactate 
and dextrose supplementation; 0.9% NaCl 
• Potassium chloride supplementation 
essential (see Hypokalemia).
• Phosphate supplements usually needed 
(see Hypophosphatemia) at initial feeding; 
often started prophylactically, see below.
• Magnesium supplements rarely needed.
Correct Hypophosphatemia
• Serum phosphate <2.0 mg/dL reflects 
refeeding syndrome; may provoke anorexia, 
vomiting, weakness, myonecrosis, ileus, 
hemolysis, coagulopathy, neurologic signs 
confused with HE.
• T reatment—potassium phosphate initial 
dose 0.01–0.03 mmol/kg/h IV; monitor 
serum phosphate q6h; discontinue when 
stable phosphate >2 mg/dL; caution : 
judiciously reduce IV potassium chloride 
supplements concurrently given in fluids; 
monitor potassium.
Correct Hepatic and Circulating GSH 
Depletion
• Low liver glutathione (GSH) confirmed 
in HL; routine GSH measurements not 
available.• Crisis intervention for low hepatic GSH or 
Heinz body anemia— N-acetylcysteine 
(NAC) 140 mg/kg IV, then 70 mg/kg IV, 
10% solution diluted 1 : 2 in saline; 
administered over 20 min otherwise may 
provoke hyperammonemia.
• When enteral feeding established, change to 
S-adenosylmethionine (SAMe) 200 mg/cat 
PO q24h; need for dosing on empty stomach 
complicates use.
ACTIVITY
Physical activity (walking), when possible, 
may increase gastric motility when 
gastroparesis complicates feeding (chronic 
vomiting).
DIET
• Nutritional support—cornerstone of recovery.
• High-protein, high-calorie balanced feline 
diet essential.
• Energy—50–60 kcal/kg ideal weight/day; 
gradual transition to full energy requirement 
over 3–7 days; feed multiple small meals/day 
or trickle feed through esophageal feeding 
tube (E-tube).
• Forced alimentation usually required; 
caution : oral forced feeding may provoke food 
aversion syndrome.
• Correct hypokalemia and hydration before 
commencing feeding; associated gastroparesis 
may lead to vomiting and potential for 
• T ube feeding—initially by nasogastric tube 
(first 1–2 days after electrolyte and vitamin 
deficiency improved), transition to E-tube after 
hydration and electrolyte status improves, and 
vitamin K1 protocol administered.
• Avoid laparotomy for gastric feeding tube 
insertion; cats with HL have high risk for 
mortality with general anesthesia and surgery; 
E-tube preferable.
• Cautiously offer PO food daily to assess 
interest.
• Human stress formula enteral diets (not 
recommended)—require supplemental 
arginine (or citrulline), and taurine; use feline 
formulated liquified diet with vitamin 
supplements.
• Supplements improve survival in severely 
• Water-soluble vitamins—in IV fluids; 
generally 2 mL/L.
• Thiamin—50–100 mg/day, give PO rather 
than SC/IM, also add via water-soluble 
vitamins mixed in IV fluids.
• Vitamin B12—initially 0.25–1 mg IM/SC 
once): determine chronic vitamin B12 needs 
by sequential B12 values (weekly, q2 weeks, to 
monthly then quarterly intervals).
• Medical-grade l-carnitine (250–500 mg/
day); over-the-counter carnitine supplements 
have wide variability in bioavailability; 
Carnitor® (liquid medical-grade carnitine) 
recommended.• Taurine 250–500 mg/day PO.
• Vitamin E 10 IU/kg/day PO in food- use 
water-soluble form initially.
• Thiol donors IV NAC, PO SAMe—as above.
• Potassium gluconate (for hypokalemia) PO, 
reduce fluid potassium supplements.
• Marine oil in food 2000 mg q24h.
• Warn client—sequential biochemical 
assessments needed to monitor recovery.
• Educate client about feeding tube use/care 
and need for chronic use (up to 4–6 months).
• Advise client—recurrence unlikely; liver 
function will not be chronically 
compromised.
• Avoid surgical interventions until 
normalization of hydration, electrolyte 
depletions, and supplements of vitamins 
provided, Heinz body anemia alleviated.
• Exploratory laparotomy and liver biopsy—
only indicated if failure to improve on 
described interventions or marked increase in 
GGT activity to identify underlying 
disorders; biopsy liver, pancreas, stomach, and 
small bowel if explored; lymph nodes if 
enlarged.
• Vitamin K1—recommended for all cats 
with suspected HL; see above, avoid 
overdosage.
• Drugs to ameliorate HE (see Hepatic 
Encephalopathy), rarely.
• Emesis control—metoclopramide: for 
vomiting, nausea, gastroparesis (0.2–0.5 mg/kg 
SC q8h 30 min before feeding, or as CRI IV 
drip at 0.01–0.02 mg/kg/h or 1–2 mg/kg/day); 
dolasetron or ondansetron; or maropitant (1 mg/
kg IV/SC/PO q24h 5 days max); pantoprazole 
to avert esophageal damage secondary to 
vomiting (0.5–1.0 mg/kg q12–24h).
• Systemic antibiotics—as appropriate for 
suspected infection.
CONTRAINDICATIONS/PRECAUTIONS
• Downward adjust dosages of medications 
relying on hepatic metabolism or excretion.
• Avoid benzodiazepines and barbiturates—
may provoke HE.
• Appetite stimulants do not provide 
dependable energy intake in cats with HL; 
some produce sedation; diazepam may cause 
rare fulminant hepatic failure.
• Avoid injectable medications with 
propylene glycol carrier; may lead to 
hemolysis in cats with low GSH.
• Ursodeoxycholic acid—likely not beneficial; 
may promote taurine deficiency.
• Dextrose supplements—may provoke 
hepatic triglyceride accumulation.Hepatic Lipidosis  (continued)

Canine and Feline, Seventh Edition  619
H• Avoid tetracyclines or stanozolol—promote 
hepatocyte triglyceride vacuolation.
• Avoid recurrent or prolonged use of 
propofol—may provoke hemolysis (12h after 
infusion) esp. in cats with Heinz body 
anemia; HL cats may recover slowly; 
alternatively use gas anesthesia.
  FOLLOW-UP
• Bodyweight and condition, hydration, 
electrolytes; judicious adjustment of energy, 
fluid, electrolyte, and vitamin provisions 
• Serum bilirubin—predicts recovery.
• Reduced lactate and ketones reconcile with 
metabolic improvement.
• Liver enzyme activity—do not predict 
recovery.
• Discharge for home care—when vomiting 
controlled, gastroparesis resolved, bilirubin 
declining, patient ambulatory, and tube-
feeding apparatus problem-free.
• T ube feeding—discontinued only after 
confirmed voluntary food consumption.
• Obesity—prevent; weight reduction must 
not exceed 2% bodyweight per week.
• Caution owner to verify food intake during 
weight loss regimens and at-home stress.
• Feeding tube malfunction or obstruction—
tube obstructions relieved with papaya juice, 
carbonated soft drink, or pancreatic enzyme 
slurry; 15 min dwell time, warm water flush.
• Rare HE after dietary support introduced.
• Unremitting HL can lead to lethal hepatic 
failure.• Untreatable underlying causal disorder.
• Optimal response to tube feeding and 
nutritional supplements—recovery in 3–6 
weeks.
• Therapy as described—85% recovery in 
severely affected animals with controllable 
primary disease process that provoked HL.
• Underlying disease influences outcome.
• HL rarely recurs.
• HL does not cause chronic liver dysfunction, 
hepatitis, persistent remodeling.
• Primary liver disorders.
• Malassimilation—various causes but IBD 
predominant.
• Diabetes mellitus—relatively uncommon.
• Neoplasia—hepatic and systemic.
• HE (rare).
• Systemic illness limiting food intake.
SYNONYMS
• Fatty liver syndrome.
• Hepatosteatosis.
• Feline hepatic vacuolation.
• Vacuolar hepatopathy.
• Vacuolar degeneration.
SEE ALSO
• APTT = activated partial thromboplastin time.• AST = aspartate aminotransferase.
syndrome.
Center SA. Feline hepatic lipidosis. Vet Clin 
North Am Small Anim Pract 2005, 
35:225–269.
Center SA, Warner KL, Randolph JF , et al. 
Influence of dietary supplementation with 
(L)-carnitine on metabolic rate, fatty acid 
oxidation, body condition, and weight loss 
in overweight cats. Am J Vet Res 2012, 
73:1002–1015.
Kuzi S, Segev G, Kedar S, et al. Prognostic 
markers in feline hepatic lipidosis: a 
retrospective study of 71 cats. Vet Rec. 
2017, 181(19):512. doi: 10.1136/
vr.104252
available online(continued)  Hepatic Lipidosis

620  Blackwell’s Five-Minute Veterinary Consult  
HHepatic Nodular Hyperplasia and Dysplastic Hyperplasia
  BASICS
OVERVIEW
Hepatic Nodular Hyperplasia (HNH)
• Benign parenchymal feature in middle-aged 
to older dogs; nonencapsulated, ≤2 cm (rarely 
up to 5 cm), expansile nodule of hepatocellular 
hyperplasia, maintaining a modified lobular 
architecture with recognizable central and 
portal elements that are irregularly spaced, 
organized hepatic cord structure 1 cell wide, 
without marginal parenchymal collapse or 
fibrosis (is not a regenerative nodule), smooth 
margins; hepatocyte phenotype may be similar 
to surrounding parenchyma but may contain 
glycogen of lipid vacuoles.
• May associate with increased liver enzymes 
in elderly dogs, especially alkaline 
phosphatase (ALP).
• Clinical concern derives from association 
with increased liver enzyme activity and US 
detection of hepatic nodules or hepatic 
nodularity during exploratory surgery.
• Variable US appearance.
• Biopsy specimens must include affected 
and unaffected liver for appropriate 
interpretation.
• Nodular hyperplasia may be mistaken for 
regeneration secondary to chronic hepatitis or 
hepatocellular neoplasia (adenoma) with needle 
core biopsies or when only nodular tissue 
without normal hepatic tissue is sampled.
Hepatocellular Dysplastic Hyperplasia 
(HDH)
• Potentially preneoplastic proliferative 
hepatocellular foci in dogs with glycogen-type 
vacuolar hepatopathy (VH); nonencapsulated, 
variably sized, reduced reticulin substructure, 
expansile nodules of nonvacuolated hepato -
cytes forming wide (2 cells wide, normal = 
1 cell width) disorganized hepatic cords, an 
irregular (serrated) margin interfacing with 
adjacent “normal VH” affected hepatocytes, 
and lacking remodeled marginal lesions 
(fibrosis, parenchymal collapse).
• Associates with VH-related increased liver 
enzymes, dominated by increased ALP 
activity.
• Recognized as an antecedent hepatic lesion 
in dogs developing hepatocellular carcinoma 
(e.g., Scottish terriers, also other breeds) and 
is seemingly associated with increased sex 
hormone concentrations (androgens, 
progestins).
• Variable US appearance depending on size, 
number, distribution.
• May be mistaken for nodular regeneration 
without special stains to detail reticulin 
substructure and collagen fibril deposition.SIGNALMENT
HNH
• Age-related lesion.
• Nodules develop by 6–8 years of age; one 
study documented lesions in all geriatric dogs 
>14 years of age.
HDH
• Associated with glycogen-type VH.
• Reflects adrenal hyperplasia syndromes.
SIGNS
• HNH does not cause clinical illness.
• Large nodules that rupture and bleed or 
nodules impairing hepatic sinusoidal 
perfusion likely represent misdiagnosed 
hepatic adenomas or well-differentiated 
hepatocellular carcinoma.
• HDH is associated with glycogen-type VH 
syndromes (see Glycogen-Type Vacuolar 
Hepatopathy).
• HNH etiology—unknown; metabolic 
factors, prior injurious events. In humans 
associated with infarcts, but no evidence of 
this in dogs.
• HDH etiology—may represent hormonal 
influence promoting neoplastic transformation 
(sex hormone–related adrenal hyperplasia).
  DIAGNOSIS
• Necroinflammatory liver disease— 
regenerative nodular hyperplasia involves the 
entire liver; formation of irregular nodules of 
variable size that are segregated by parenchymal 
collapse, often marginated by fibrous connective 
tissue; demonstrate loss of lobular architecture, 
sinusoidal fibrosis, reduced reticulin 
substructure, and wide disorganized hepatic 
cords.
• Neoplasia—hepatic adenoma: mass lesions 
with margins reflecting expansile compression 
on normal adjacent liver, encapsulated, 
hepatic cords double wide, disorganized, 
reduced reticulin substructure, and minimal 
atypia. Hepatocellular carcinoma: single or 
multiple confluent or separate mass lesions, 
margins reflecting irregular expansile 
compression on normal adjacent liver, 
partially encapsulated, variable width of 
disorganized hepatic cords >2 cells, multiple 
phenotypes differing from adjacent normal 
tissue, variable atypia (may be well 
differentiated), may display pseudoglandular 
pattern associated with giant canaliculi, 
well-vascularized with arterial twigs; retention 
of some normal lobular elements possible 
(primarily at the periphery).CBC/BIOCHEMISTRY/URINALYSIS
• CBC—no association with HNH; for HDH 
see Glycogen-Type Vacuolar Hepatopathy.
• Biochemistry profile—increased serum ALP 
activity may be encountered with HNH and 
HDH; may range from 2.5- to 16-fold 
normal; higher with HDH and VH 
syndrome, see Glycogen-Type Vacuolar 
Hepatopathy; usually normal total protein, 
albumin, bilirubin, and cholesterol.
• Urinalysis—no consistent findings.
Total serum bile acids (TSBA)—usually 
normal, unless lesions are diffuse and severe.
IMAGING
• Abdominal radiography—no abnormalities 
except hepatomegaly with HDH due to VH.
• Abdominal US—variable echogenicity 
relating to histologic features, nodule number 
and size, and associated VH. HNH often not 
noted until liver grossly inspected at surgery 
or laparoscopy.
• Aspiration cytology—may yield normal 
hepatocytes, hepatocytes with cytosolic 
rarefication and fragility consistent with VH 
(glycogen retention), or cells with discrete lipid 
(triglyceride) vacuoles (HNH); occasional 
binucleate hepatocytes may reflect cell 
proliferation or other concurrent disease 
(common in portosystemic  vascular anomalies/
microvascular dysplasia); hepatocytes may be 
small with size variation in HDH. Liver 
biopsy—  collection of a needle biopsy 
specimen may not clearly differentiate HNH 
lesion because of small specimen size; 
definitive diagnosis requires targeted sampling 
of a large enough tissue specimen to include 
lesion and adjacent normal hepatic tissue. 
HDH may be recognized on needle samples.
• Recommended biopsy methods—  laparoscopy, 
open-wedge biopsy during laparotomy, or 
multiple 14-G needle samples.
• Special stains—reticulin staining illustrates 
hepatocyte reticulin substructure, lobular 
collapse/remodeling, and changes associated 
with nodule margins. Masson’s trichrome 
staining illustrates collagen deposition and 
remodeling typical of regenerative nodules 
secondary to chronic liver injury; periodic 
acid-Schiff staining with and without amylase 
predigestion confirms excess glycogen in 
vacuolated hepatocytes (see Glycogen-Type 
Vacuolar Hepatopathy).
• HNH gross—single or multiple mass 
lesions, rarely >2 cm in diameter; color 
similar to adjacent normal hepatic tissue or 
paler if vacuolated with glycogen or lipid.
• HDH gross—single or multiple lesions, 
usually small, may appear darker colored 
compared to adjacent tissue. Microscopic—
see above.

Canine and Feline, Seventh Edition  621
H  TREATMENT
• Usually none required; rupture of large 
nodules indicates hepatocellular carcinoma 
misdiagnosis; may necessitate blood 
transfusion and emergency mass excision. 
Palliate or alleviate underlying cause of VH.
• HDH—recommend biochemical assessments 
for rising ALP or alanine aminotransferase 
(ALT) that may indicate transformation of mass 
lesion to a neoplastic phenotype; US inspection 
of adrenal glands for adrenomegaly or nodules, 
US surveillance for expanding mass lesions that 
should be surgically removed; assess pituitary 
adrenal axis for typical or atypical hyperadreno -
corticism; if increased sex hormones >2.5 × 
upper reference interval consider adrenal 
modulation with agent that does not increase 
sex hormones.
• HDH—if increased sex hormones, 
progressive VH, nodule formation, increasing 
ALP , or confirmed hepatocellular carcinoma 
(after mass resection), consider adrenal 
modulation with a drug that does not increase 
sex hormone concentrations (Lysodren® or 
mitotane); trilostane increases sex hormone 
concentrations and would be inappropriate.• Scottish terrier syndrome does not 
respond to adrenal modulation; instead use 
surveillance to detect emerging hepatocellular 
  FOLLOW-UP
• Quarterly biochemical profiles.
• Sequential abdominal US to evaluate 
progression of hepatic nodules.
• See Glycogen-Type Vacuolar Hepatopathy 
for related disorders.
Distinction of HNH from neoplastic foci is 
not possible based only on clinical, laboratory, 
or imaging data, although lesions >2 cm are 
unlikely to be this diagnosis.
More extensive numbers of nodules may 
develop in some dogs with HNH and HDH; 
HDH predicts risk for primary hepatocellular 
neoplasia, which requires surveillance and 
surgical treatment.
SEE ALSO
• Glycogen-Type Vacuolar Hepatopathy.• Hepatitis, Chronic.
• Hepatocellular Adenoma.
• Hepatocellular Carcinoma.
• HDH = hepatic dysplastic hyperplasia.
• HNH = hepatic nodular hyperplasia.
(1993–2005). J Am Vet Med Assoc 2006, 
Stowater JL, Lamb CR, Schelling SH. 
Ultrasonographic features of canine hepatic 
nodular hyperplasia. Vet Radiol 1990, 
31:268–272.
Sean P . McDonough.(continued)  Hepatic Nodular Hyperplasia and Dysplastic Hyperplasia

622  Blackwell’s Five-Minute Veterinary Consult  
HHepatitis, Chronic
  BASICS
• Hepatic injury associated with active 
chronic necroinflammatory liver injury; 
“chronic active hepatitis” should not be used.
• Nonsuppurative inflammation—most 
common; lymphocytes, plasma cells, 
macrophages, occasional neutrophils.
• Chronicity—progressive remodeling, 
regenerative nodule formation, evolving 
sinusoidal fibrosis with location dependent on 
zonal tropism of inflammation; changes 
eventuate in cirrhosis.
• A multitude of initiating events or agents 
cause hepatic injury; damage to cell and/or 
organelle membranes usually involves 
oxidative injury; activated cytokines and 
cell-mediated immune responses widen and 
perpetuate inflammation; hepatic neoepitopes 
may become targeted foci.
• Initial injury may include infectious agents, 
toxins, xenobiotics, or pathologic Cu 
accumulation; with exception of Cu-mediated 
injury, cause often remains undetermined.
• Inflammatory cells—predominantly 
lymphocytes, fewer Kupffer cells (resident 
hepatic sinusoidal macrophages), and variable 
neutrophils are initial effectors.
• Injury zone demarcates area of predominant 
necroinflammatory damage—zone 1 
(periportal) common to idiopathic hepatitis 
or inflammation involving portal tract 
structures; zone 3 incriminates Cu, 
nonsteroidal anti-inflammatory drug (NSAID), 
other xenobiotic or toxin-mediated injury, or 
repeated ischemic/hypoxic insult; panlobular 
inflammation common.
• Lesion progression—variable, may include 
portal and periportal lymphoplasmacytic 
infiltrates with interface hepatitis (inflammation 
breaching limiting plate of portal tract), and 
otherwise variable lobular injury; chronic 
inflammation: leads to progressive fibrosis with 
bridging of involved zones.
• Bridging fibrosis and regenerative nodules 
distort lobular architecture; fibrosis, 
intrahepatic sinusoidal hypertension, 
neovascularization, and impaired hepatic 
function evolve into cirrhosis.
• Progressive cholestasis due to mechanical 
compression/distortion of bile ducts may 
occur.
• Cirrhosis and hepatic failure—late stage.
• Fibrosis—usually reflects chronic injury 
from sustained inflammation.
• Cirrhosis—associated with hepatic 
dysfunction, sinusoidal hypertension; 
intrahepatic shunting through collagenized 
sinusoids or neovascular pathways in fibrotic 
partitions that segregate regenerative nodules.• Sinusoidal hypertension—leads to hepato -
fugal portal circulation (flow away from liver); 
mesenteric splanchnic hypertension; develop -
ment of acquired portosystemic shunt(s) 
(APSS); episodic hepatic encephalopathy (HE); 
ascites; portal hypertensive enteric vasculopathy 
predisposes to enteric bleeding.
• Hepatobiliary—inflammation; necrosis; 
cholestasis; fibrosis.
• Gastrointestinal (GI)—emesis; diarrhea; 
anorexia, portal hypertension, ascites, and 
propensity for enteric bleeding.
• Neurologic—HE (advanced stage, 
associated with APSS).
• Hemic—red blood cell (RBC) microcytosis 
reflects APSS; bleeding or thrombotic 
tendencies: failed factor or anticoagulant 
synthesis or activation, thrombocytopenia or 
thrombopathia; coagulopathies typically 
observed with advanced injury or severe 
diffuse hepatic necrosis.
• Renal/urologic—polyuria/polydipsia (PU/
PD); isosthenuria; ammonium biurate 
crystalluria (advanced stage with APSS and HE).
end-stage liver failure.
• Respiratory—tachypnea if tense ascites; 
bicavitary effusion or pulmonary edema.
GENETICS
• Breed or familial predisposition for chronic 
hepatitis—Doberman pinscher, Labrador 
retriever, West Highland white terrier, and 
Dalmatian may develop chronic hepatitis 
secondary to pathologic Cu accumulation; 
cocker spaniel hepatopathy, anecdotal in 
other breeds or breeding lines.
• Inherited Cu associated hepatopathy only 
proven in Bedlington terrier— autosomal 
recessive, genetic test available.
Species
Dog
Average age 6–8 years (range: 2–14 years).
Inconsistent among reports for any breed.
SIGNS
• Initially—vague and nonspecific, often 
includes lethargy and inappetence.
hypertension; impaired hepatic function 
including cholestasis.
• May be no signs in early disease or mild 
lethargy.
• Anorexia, vomiting, weight loss, reduced 
body condition.• PU/PD.
• Jaundice—later stage unless portal hepatitis 
involves bile duct injury.
• Ascites—late stage.
• HE—late stage, infers APSS with cirrhosis.
• May be no signs in early disease.
• Lethargy, poor coat, declining body 
• Liver size—normal to small, depends on 
chronicity.
Late-Stage Physical Findings
• Ascites.
• HE.
biurates.
• Bleeding or thrombotic tendencies.
CAUSES
• Chronic necroinflammatory, oxidant, and 
immune-mediated liver injury has many causes.
• Infectious—canine hepatitis virus; lepto -
spirosis, enteric-portal bacteremia or endotox -
emia affiliated with inflammatory bowel 
disease; accidental parenteral administration of 
intranasal Bordetella  vaccine.
• Immune-mediated—autoimmune with 
positive antinuclear antibody (ANA); acquired 
immune sensitization, nonsuppurative 
• Toxic—Cu associated hepatopathy; acute 
or chronic exposure to drugs—predictable or 
idiosyncratic toxicity: e.g., azole antifungals, 
trimethoprim-sulfa, zonisamide, pheno -
barbital, primidone, phenytoin, CCNU, 
NSAIDs (esp. carprofen); repeat exposure to 
environmental or food-borne toxins, e.g., 
dimethylnitrosamine, aflatoxin, cycad, 
cyanobacteria.
• Immunostimulants (vaccinations?) and 
molecular mimicry of cell epitopes by 
infectious agents or infection of sinusoidal 
endothelium.
• Cu associated hepatopathy.
• Hepatic iron accumulation—from 
inappropriate supplementation.
• Xenobiotics (drugs, herbal, holistic, or 
Chinese remedies), inducers or inhibitors of 
microsomal enzymes, impaired hepatic 
antioxidant status; xenobiotic metabolites 
foster inflammation or augment direct initial 
  DIAGNOSIS
• Acute hepatitis—history, sequential 
biochemistry profiles or liver biopsy.
• Congenital portosystemic shunt 
(portosystemic vascular anomaly [PSVA]).

Canine and Feline, Seventh Edition  623
H• Primary hepatic neoplasia.
• Metastatic neoplasia or carcinomatosis.
• Chronic pancreatitis.
• Other causes of abdominal effusion—
hypoalbuminemia; passive congestion; 
carcinomatosis; chemical peritonitis (bile, 
urine, pancreatitis), hepatic or nonhepatic 
causes of portal hypertension: see 
Hypertension, Portal.
• Jaundice—extrahepatic bile duct occlusion 
(EHBDO); bile peritonitis, cholangitis/
cholangiohepatitis syndrome, ductopenia, 
Hemogram
CBC—nonregenerative anemia; RBC 
microcytosis if APSS; variable leukogram, 
occasional thrombocytopenia; low total 
protein if chronic disease with synthetic 
failure and portal hypertension causing 
enteric protein loss.
High liver enzymes; variable bilirubin, 
albumin, blood urea nitrogen (BUN), 
glucose, cholesterol; hepatic failure—sug-
gested by low albumin, BUN, glucose, and 
cholesterol in absence of alternative causes.
Variable urine concentration; escalated 
bilirubinuria; ammonium biurate crystalluria 
if APSS.
• Total serum bile acids (TSBA)—variable; 
depends on extent of hepatic remodeling, 
sinusoidal hypertension, and cholestasis; 
superfluous test if hepatic hyperbilirubinemia .
• Ammonia intolerance—reflects APSS; 
insensitive to cholestasis, lability impairs 
accuracy.
• Coagulation tests—reflect panlobular injury, 
chronicity, vascular injury, impaired synthetic 
capacity or vitamin K adequacy; early disease: 
few abnormalities except possible high 
fibrinogen; advanced stage or severe pan -
lobular injury: single or multiple abnormali -
ties including prolonged prothrombin, 
activated partial thromboplastin time, low 
fibrinogen, increased D-dimers.
• Low protein C or antithrombin activity—
may reflect PSVA, APSS, hepatic failure, or 
consumptive coagulopathy.
• Abdominal effusion—chronic liver disease 
portal hypertension: pure or modified 
transudate.
• Liver tissue zinc—low with chronic disease 
and APSS.
• Serologic or PCR tests—possible infectious 
agents, e.g., leptospirosis, rickettsial diseases, 
Borrelia , Bartonella , endemic fungal agents.
• ANA titer—if potential for autoimmune 
disease; note: low-level positive titers 
nonspecific and more common with 
advanced age.• Immunohistochemical staining of liver 
biopsy—can confirm infectious agents or 
phenotype of infiltrating cells (inflammatory 
or neoplastic).
IMAGING
• Microhepatia—suggests late-stage disease or 
APSS causing lobular atrophy.
• Abdominal effusion—obscures image.
• Ammonium biurate calculi—radiolucent 
unless combined with radiodense minerals.
US
• Liver size depends on disease stage.
• Normal to variable parenchymal and biliary 
tract echogenicity; may note nodularity and 
irregular liver margins with chronicity due to 
regenerative nodules.
• APSS—tortuous vessels most commonly 
identified caudal to left kidney or near splenic 
vein.
• Abdominal effusion—US facilitates fluid 
sampling.
• Uroliths—renal pelvis or urinary bladder; 
may signify ammonium biurate urolithiasis 
but cannot differentiate mineral composition 
without stone analysis.
• Rule out—EHBDO; identify mass lesions; 
cholelithiasis; gallbladder mucocele (GBM); 
cholecystitis; choledochitis; cystic lesions 
(abscess or ductal plate malformation–related).
• Enables fine-needle aspiration—cytology 
and cholecystocentesis for bile collection.
Colorectal/Splenoportal Scintigraphy 
(CRS/SPS)
• 99MTechnicium pertechnetate isotope time 
activity curve displays chronologic isotope 
distribution: delivery to liver first = no 
shunting, delivery to heart first = shunting.
• CRS—sensitive, noninvasive; cannot 
differentiate PSVA from APSS.
• SPS—no diagnostic advantage, US-guided 
splenic injection, uses a lower isotope dose and 
therefore has faster discharge from hospital.
Aspiration Cytology
• Fine-needle aspiration cytology— cannot 
define  fibrosis or nonsuppurative 
inflammation ; cannot  recommend therapy.
• Cannot definitively diagnose chronic 
hepatitis, hepatic fibrosis, or Cu associated 
hepatopathy.
Liver Biopsy
• Liver biopsy—needed for definitive diagnosis; 
acquire biopsies from multiple liver lobes.
• T ru-Cut® needle biopsy—use 14–16 G.
• Laparoscopy—best biopsy method; lower 
morbidity and faster recovery vs. exploratory 
laparotomy.
Bacterial Culture
Aerobic and anaerobic bacterial culture and 
sensitivity of liver and bile; use particulate 
biliary debris if possible.Metal Analyses
• Measure Cu, iron, and zinc concentrations 
in liver (dry matter basis).
• Low hepatic zinc associated with portosystemic 
shunting requires supplementation.
• Iron commonly accumulates in 
necroinflammatory disorders; must be reconciled 
with distribution for relevance: e.g., Prussian 
blue staining defines distribution in macrophages 
(chronic inflammation) vs. predominantly in 
hepatocytes (hemochromatosis).
• Cu quantification and rhodanine staining—  
ascertains relevance to parenchymal injury.
• Gross—early: no gross change; late stage: 
irregular surface contours, microhepatica, ± 
tortuous APSS varices.
• Microscopic—nonsuppurative inflammation 
in zone(s) of necroinflammatory injury; 
variable cholestasis and biliary hyperplasia; 
interface hepatitis: invasion of limiting plate; 
late-stage disease: fibrotic bridging partitions 
between or within involved zones and 
marginating regenerative nodules, sinusoidal 
dissecting fibrosis; final transition to  
cirrhosis.
lobular, centrilobular, or panlobular with 
lymphoplasmacytic infiltrates, hepatic cord 
injury causing disorganization, sinusoidal 
fibrosis, biliary hyperplasia.
• Cu associated hepatopathy—initially 
centrilobular, may evolve panlobular 
immune-mediated hepatitis.
• Cirrhosis—diffuse, unresolvable; fibrosis, 
nodular regeneration distorting lobular 
architecture.
  TREATMENT
• Inpatient—for diagnostic testing, supportive 
care, treatment initiation in severe illness.
• Outpatient—if condition stable at diagnosis; 
slowly titrated onto medical therapy.
• Fluid therapy—balanced polyionic fluids 
supplemented to correct hydration, electrolyte 
aberrations, or hypoglycemia; restricted 
sodium if ascites, may require fresh frozen 
plasma, avoid synthetic colloids.
• Water-soluble vitamins—2 mL/L fluids.
• Ascites (see Cirrhosis and Fibrosis of the 
Liver).
ACTIVITY
Keep patient warm and hydrated; restricted 
activity may improve hepatic regeneration, 
euglycemia, and ascites mobilization.(continued)  Hepatitis, Chronic

624  Blackwell’s Five-Minute Veterinary Consult  
HDIET
• Conserve body condition and muscle mass.
• Adequate calories and protein—to avoid 
negative nitrogen balance and catabolism.
• Dietary protein—restrict protein quantity 
only if signs of HE or observe ammonium 
biurate crystalluria; feed balanced species-
specific diet; if HE, avoid fish and red meat 
source protein (dogs).
• Fat restriction rarely needed.
• If Cu associated liver injury, see Copper 
Associated Hepatopathy.
• Meal frequency—feed several small meals 
per day.
• Sodium restriction—with ascites or severe 
hypoalbuminemia: <100 mg/100 kcal or 
<0.2% dry matter basis formula.
• Balanced vitamin supplements (water 
soluble, fat soluble)— increased urinary 
water-soluble vitamin loss if PU/PD or 
diuretic therapy.
• Thiamin—ensure repletion to avoid 
metabolic complications and neurologic 
signs; 50–100 mg PO q24h; caution : 
injectable thiamin.
• Partial parenteral nutrition—may consider, 
insufficient to meet energy requirements.
• Total parenteral nutrition—if inappetence 
>7 days; branched-chain amino acids remain 
controversial in dogs with liver dysfunction.
• Control rather than cure is expected goal; 
medications usually required for life; chronic 
hepatitis is cyclic and will minimally require 
reevaluations q4–6 months after initial 
control.
• Antifibrotics—best control of fibrosis 
through control of inflammation and 
underlying primary process.
dehydration; azotemia, infection; catabolism; 
constipation; hypokalemia; alkalemia; high- 
protein meals; endoparasitism; enteric 
• APSS—do not ligate APSS or band vena 
cava.
anesthesia preferred: isoflurane or sevoflurane.
• T reatments for specific etiologies.
• Withdraw plausible hepatotoxic drugs.
therapeutic regimens at this time.
Immunomodulation
• Prednisolone/prednisone —1–2 mg/kg 
daily PO; taper to lowest effective dose 
(0.25–0.5 mg/kg PO q48h); if ascites: use dexamethasone to avoid mineralocorticoid 
effects (divide prednisone dose by 7–10 for 
dexamethasone dose), SID q2–3 days.
• Azathioprine— dogs: 2 mg/kg (50 mg/m2) 
PO q24h × 14 days then titrate to q48h; 
contraindicated in cats (toxic); dogs: combine 
with prednisone, antioxidants, antifibrotic 
polyunsaturated phosphatidylcholine (PPC); 
during chronic therapy, titrate by 25–50% dose 
reduction after 2–6 months based on 
sequential biochemistries showing improve -
ments (e.g., normalization of total bilirubin 
and marked decline in liver enzyme activity); 
monitor CBC and biochemistry profile q7–14 
days for first 2 months to ensure absence of 
hematopoietic, hepatic, or pancreatic toxicity; 
if acute hematopoietic toxicity, stop therapy, 
allow recovery, then reintroduce with 25% dose 
reduction; if insidious chronic hematopoietic 
toxicity (after months) or acute cholestatic 
liver or pancreatic injury, discontinue therapy 
and change to different drug (e.g., mycopheno -
late or cyclosporin); risk for neoplasia with 
chronic use.
• Mycophenolate mofetil— 10–15 mg/kg PO 
q12h; doses ≥10 mg/kg PO BID may lead to 
diarrhea’ start lower initial dose and/or divide 
total daily dose into 3–4 doses to reduce toxic 
effects; monitor as for azathioprine and adjust 
similarly; fewer bone marrow side effects than 
azathioprine but more GI toxicity; avoid 
dosing with food or after administration of 
proton pump inhibitor as these factors 
reduce drug bioavailability; if failure to 
respond to azathioprine go to cyclosporin vs. 
mycophenolate; if azathioprine toxicity go to 
mycophenolate.
• Microemulsified cyclosporine  (Atopica®)—  
2.5–5 mg/kg PO q24h; use with glucocorti -
coids may increase drug efficacy and permit 
lower dose; side effects: gingival hyperplasia 
(managed with azithromycin), rare cholestatic 
liver injury, hyperlipidemia, hypercholester -
olemia, worsening preexistent hypertension, 
risk for GB disease, risk for opportunistic 
infections; high dose can lead to nephrotoxic -
ity; risk for neoplasia with chronic use; avoid 
concurrent use of p450 inhibitors unless 
cyclosporin dose substantially reduced.
Hepatomembranoprotectant, immuno -
modulatory, antifibrotic, choleretic, anti-
endotoxic, and antioxidant effects; 
10–15 mg/kg PO SID or divided q12h; 
administer with food for best bioavailability; 
may use as aqueous solution; no deleterious 
side effects; maintain indefinitely.
• Immunomodulators, S-adenosylmethionine 
(SAMe), vitamin E.
• Polyunsaturated phosphatidylcholine  (PPC, 
dilinolylphosphatidylcholine [DLPC]) —PPC 
containing DLPC antifibrotic, has immuno -
modulatory, antioxidant, hepatoprotectant effects, and improves membrane fluidity; 
25–50 mg/kg/day PO with food; PhosChol® 
with preformed DLPC (52%) has benefit in 
some forms of liver disease (humans, animal 
models); may have corticosteroid-sparing 
effect (allows reduced glucocorticoid dosing); 
safely prescribed without liver biopsy.
• Colchicine— not recommended.
• Silybin with PPC  (milk thistle)—
experimental studies suggest potential 
hepatoprotectant (against numerous toxins), 
antifibrotic, antioxidant effects, and possibly 
promoting hepatocyte regeneration; low 
bioavailability of oral forms significantly 
limits biologic effect at traditional oral 
dosing: 2–5 mg/kg/day PO (PPC complexed 
form); only bioavailable form IV formulation 
(Legalon® SIL) used for Amanita  death cap 
mushroom toxicity with high dose protocol; 
orphan drug.
• Vitamin E— α-tocopherol, 10 IU/kg PO 
q24h with food.
• SAMe—20 mg/kg/day enteric-coated 
tablet PO, give on empty stomach for best 
bioavailability, 1–2h before feeding.
• Avoid vitamin C (ascorbate).
• Zinc (zinc acetate)—has antioxidant and 
antifibrotic benefits, supplementation may 
improve control of HE if low liver zinc 
concentration documented, unreliable for 
limiting enteric Cu uptake; elemental zinc 
1.5–3 mg/kg PO daily as supplement if low 
liver zinc concentration (<120  μg/g dry 
weight liver); adjust dose using sequential 
plasma zinc concentrations that show 
increased concentrations; avoid plasma 
concentrations ≥800  μg/dL to prevent 
hemolysis; plasma zinc levels do not correlate 
with tissue levels.
• Ursodeoxycholate, vitamin E, SAMe, 
PPC—provide hepatoprotectant effects in 
addition to other benefits.
• Silybin—see above.
GI Signs/Vomiting/Hematemesis
• HCl pump inhibitors—omeprazole 
0.5–1.0 mg/kg q12–24h PO or pantoprazole 
0.7–1 mg/kg q12h IV, better long-term 
control vs. famotidine.
• Sucralfate—gastroprotectant dose 0.25–
1.0 g/10 kg PO q8–12h; titrated to effect; 
beware of drug interactions as sucralfate 
may bind other medications, reducing 
bioavailability.
• NSAIDs—avoid; may provoke enteric 
ulceration and bleeding; may worsen 
ascites; metabolites cause centrilobular 
hepatocyte injury.Hepatitis, Chronic  (continued)

Canine and Feline, Seventh Edition  625
H• Avoid drugs requiring extensive hepatic 
metabolism or judiciously adjust dose if APSS, 
HE, jaundice, or hepatic failure evident.
alkalosis, constipation: provoke or worsen 
HE.
• Glucocorticoids—increase susceptibility to 
infection, enteric bleeding, sodium and water 
retention (those with mineralocorticoid 
effects), PU/PD, protein catabolism, HE.
• Avoid drugs or reduce dose for those 
dependent on first-pass hepatic extraction if 
APSS or those requiring hepatic conjugation 
or biotransformation for detoxification, e.g., 
7.5 mg/kg PO q12h (often used for HE).
• Zinc overdose may cause hemolysis.
• Avoid medications altering hepatic p450 
cytochrome biotransformation/elimination 
pathways (cimetidine, quinidine, ketoconazole).
• Avoid concurrent treatment with 
metoclopramide if spironolactone used for 
diuresis (causes aldosterone release).
• Adjust dose of immunomodulators if 
used in combination to avoid 
prednisone or prednisolone with this drug to 
avoid mineralocorticoid effect; divide dose by 
7–10, administer q3 days.
• Mycophenolate—alternative if azathioprine 
intolerance, see above.
  FOLLOW-UP
• At-home behavior/cognitive function, 
bodyweight, body condition, and muscle 
mass scores monitored.
• CBC, biochemistry, urinalysis—depending 
on immunosuppressive medications (see 
above), initially q2 weeks for 2 months, then 
monthly or quarterly; depends on patient 
status and drugs administered; monitor for 
• Serial monitoring of TSBA—usually does 
not add prognostic or diagnostic information.• Abdominal girth—reflects ascites volume; 
important to standardize measurement site, 
method, and operator determining circum- 
ference.
• Azathioprine—monitor for possible bone 
marrow toxicity (serial CBCs q2 weeks for 2 
months then quarterly); leukopenia may 
develop acutely or after chronic use; GI or 
pancreatic toxicity; hepatotoxicity (alanine 
aminotransferase activity), other effects and 
opportunistic infectious complications.
• Mycophenolate—monitor for GI toxicity, 
rare bone marrow toxicity, opportunistic 
infectious complications; diarrhea most 
common complication, manage by dividing 
daily drug dose into 3–4.
• Cyclosporine—renal function, infectious 
complications, avoid cytochrome p450 
inhibitor drugs; remain aware of possible 
drug-provoked hyperlipidemia, hypercho -
lesterolemia, related GB disease (dysmotility, 
GBM, cholelithiasis).
threatening; disseminated intravascular 
coagulation—may be terminal event.
• Chronic hepatitis often cyclic; occasional 
flare-ups inconsistently associated with clinical 
illness, more consistently associated with 
vacillating liver enzymes or hyperbilirubinemia.
• Some dogs achieve solid long-term 
• Some dogs with Cu associated hepatopathy 
achieve permanent remission of apparent 
“immune-mediated” inflammation with Cu 
chelation and lifelong dietary Cu restriction.
• Development of ascites—severe liver injury, 
APSS, potential for HE, shorter survival.
• Severe disease—with APSS, HE, and ascites 
may require occasional hospitalizations to 
adjust nutritional and medical interventions.
• Dogs with leptospirosis-associated chronic 
liver disease (rare) may shed organisms.
• Bartonella  and rickettsial infections are 
sentinels for endemic vectors.SEE ALSO
• Ascites.
• Copper Associated Hepatopathy.
• CRS = colorectal scintigraphy.
• DLPC = dilinolylphosphatidylcholine.
occlusion.
drug.
• PPC = polyunsaturated 
phosphatidylcholine.
• SPS = splenoportal scintigraphy.
available online(continued)  Hepatitis, Chronic

H626  Blackwell’s Five-Minute Veterinary Consult  
HHepatitis, Granulomatous
  BASICS
• Uncommon necroinflammatory hepatitis.
• Characterized by histiocytes/macrophages, 
lymphocytes, plasma cells, and variable 
neutrophilic infiltrates forming granulomas 
that efface normal hepatic structure.
• May reflect infectious agents, immune-
mediated or immunoregulatory disorders, or 
proliferative/neoplastic histiocytic syndrome.
• May localize to liver or be multisystemic 
(spleen, lymph nodes, bone marrow, lungs).
• Copper associated hepatopathy—involves 
unique small “copper granulomas” distinct 
from this syndrome.
• Inflammatory process may be initiated by 
infection—bacteria (eubacterial, mycobacterial, 
chlamydial), viral, parasitic, protozoal, or fungal 
agents.
• May reflect immune-mediated or 
immunoregulatory disorders.
• May be initiated by adverse drug or 
xenobiotic interaction including herbal, 
holistic, or Chinese traditional remedies, or 
toxin exposure.
• May reflect proliferative histiocytic 
syndromes or histiocytic neoplasia.
• Hepatocyte necrosis—reflects insufficient 
regional perfusion and hypoxia, cytokine-
mediated cytotoxic cell injury (histiocytes, 
lymphocytes), initial direct or indirect 
hepatotoxic injury.
• Severity of hepatic dysfunction—reflects 
density and lobular distribution of injury.
• Toxins—affect zone where bioactivated or 
metabolized as initial site of lesion 
• Zone 3 copper accumulation—may 
augment zone 3 (centrilobular region) 
injury.
• Liver injury associated with enzyme 
leakage reflecting regional involvement; 
hyperbilirubinemia occurs with diffuse 
injury, canalicular damage, biliary tree 
involvement; sinusoidal injury leads to 
sinusoidal hypertension, splanchnic 
hypertension, ascites, acquired portosystemic 
shunt (APSS).
• Severe diffuse lobular involvement can lead 
to liver failure associated with complex 
coagulopathies; enteric hemorrhage may 
reflect acute splanchnic portal hypertension 
and lead to acute-onset hepatic encephalo -
pathy (HE).
• Hepatic failure—associates numerous 
metabolic derangements and detoxification 
capabilities; may be lethal.
• No breed, sex, or age predilection.
• More common in dogs than cats.SIGNS
• Nonspecific clinical signs, lethargy; abrupt 
or gradual onset of illness.
• Anorexia, vomiting, diarrhea, weight loss.
• Polyuria/polydipsia.
• Normal liver size or severe hepatomegaly.
• Abdominal pain—vague, due to hepatic 
capsule stretching.
• Distended abdomen—ascites; hepato  - 
megaly.
• ± Splenomegaly—granulomatous process.
• ± Lymphadenopathy—granulomatous 
• ± Jaundice.
• ± Fever.
• ± Tachypnea—abdominal distention due to 
ascites or pulmonary involvement.
• Late stage—bleeding tendencies, ascites, HE.
• Systemic fungal infection—histoplasmosis; 
blastomycosis; coccidioidomycosis; pythiosis.
• Bacterial infection— Brucella , Nocardia , 
Borrelia , Propionibacterium acnes , mycobacteria 
species; Bartonella , Staphylococcus , Leptospirosis , 
many other organisms.
• Rickettsial infections.
• Parasitism—visceral larval migrans; liver 
flukes, schistosomiasis; dirofilariasis.
• Virus—feline infectious peritonitis.
• Protozoal— Toxoplasma ; visceral Leishmania .
• Neoplasia—histiocytic neoplasia, lymphoma.
• Hemophagocytic histiocytic sarcoma.
• Reactive or proliferative histiocytosis.
• Immune-mediated inflammation; may be 
autoimmune lupus like syndrome.
• Drug reactions (e.g., ketoconazole).
• Xenobiotics—holistic, herbal, Chinese 
traditional remedies.
• Toxins or infectious agents disseminated in 
treats or food products from countries with 
unregulated manufacturing processes.
• Idiopathic—no recognized cause after 
meticulous investigations; may be 
autoimmune.
  DIAGNOSIS
Widely disparate features initiate pursuit of 
diagnostic considerations; drug history must 
be carefully reviewed; consideration of splenic 
and/or bone marrow involvement necessary 
to rule out histiocytic neoplasia if biopsy 
discloses mitotically active dysplastic-  
appearing histiocytes.
• CBC—inflammatory or stress leukogram; 
nonregenerative anemia; spherocytes: 
microangiopathic shearing, immune-mediated 
anemia, or histiocytic hemophagocytic syndrome; monocytosis with chronic 
inflammation/infection.
• Biochemistry—high liver enzymes; variable: 
bilirubin, hypoglycemia; hypoalbuminemia, 
low blood urea nitrogen; high or low total 
proteins; high globulins; may note electrolyte 
disturbances, hypocholesterolemia with 
hemophagocytic histiocytic sarcoma.
• Urinalysis—may be normal or demonstrate: 
bilirubinuria, proteinuria, red blood cells, 
white blood cells, cellular and other casts.
• Serum bile acid concentrations—often high 
with massive hepatic involvement or APSS.
• Coagulation assays—normal, except with 
• Acute-phase proteins may increase—certain 
globulins, fibrinogen, C-reactive protein, 
protein C, antithrombin.
• Serologic tests—evaluate titers with caution in 
regard to infectious agents; important to 
consider convalescent titers; increased immuno -
globulin M titers to toxoplasmosis or leptospiro -
sis support active infection, consider serology for 
Bartonella ; test according to plausible exposures 
considering travel history and other variables 
(e.g., raw meat diet).
• Molecular diagnostic tests—PCR or 
fluorescent in situ hybridization (FISH) for 
eubacterial organisms or other infectious 
agents not visualized on microscopy of liver 
biopsy; mycobacterial PCR and Bartonella  
PCR may warrant investigation.
• Antinuclear antibody titer—positive with 
systemic lupus erythematosus but low positive 
titers nonspecific.
• Bacterial cultures—liver tissue, bile (use 
particulate debris), or blood; mycobacterial 
cultures grow slowly (months) thus mycobac -
teria may be more promptly detected using 
PCR and tissue staining (Ziehl-Neelsen, Fite 
Faraco); however, tissue staining with 
granulomatous inflammation and mycobac -
teria may be negative (as shown in humans).
IMAGING
normal to large sized liver, abdominal 
mass(es), or ascites obscuring regional detail.
liver size and abnormal nodular parenchymal 
pattern, mass lesions, splenomegaly and 
lymphadenopathy; confirms abdominal 
effusion; enables diagnostic needle sampling 
of tissue for cytology or core liver biopsy.
• Aspiration sampling—hepatic parenchyma, 
spleen, bone marrow, and abdominal effusion.
granulomatous reaction but often does not 
define cause. Copper-specific stain and copper 
quantification in liver (dry weight basis) should 
be done to rule out, as copper granulomas 
misinterpreted as “pyogranulomatous” that

Canine and Feline, Seventh Edition  627
HHmay lead to needless evaluations; copper 
concentration can be qualitatively estimated 
from liver stained with rhodanine; see Copper 
• Special staining for infectious agents—
Gram stain, modified Steiner’s, Ziehl-Neelsen 
and Fite Faraco (mycobacteria), periodic 
acid–Schiff (fungi, amoeba, protozoa), 
Grocott’s methenamine silver (fungi, certain 
bacteria, e.g., Norcardia , Actinomyces ).
• Consider bone marrow aspirate/core if 
histiocytic neoplasm or lymphoma suspected 
or to confirm certain infectious diseases (e.g., 
mycobacteria, brucellosis, toxoplasmosis).
• Gross—hepatomegaly; normal, finely 
irregular surface, indented circular or dimpled 
pale lesions; firm texture; may have blunted 
margins and abdominal effusion.
• Microscopic—pyogranulomatous reaction, 
random or variable zonal infiltrate distribution.
  TREATMENT
• Inpatient vs. outpatient—dictated by 
severity of clinical signs.
• Fluid therapy—balanced polyionic solution 
for rehydration and maintenance needs, may 
require dextrose (2.5–5%) if hypoglycemic.
• Nutritional support essential; do not restrict 
protein if lacking signs of HE.
• Inform client that causes of this syndrome 
may be difficult to confirm and treat.
• If granulomatous response associates with 
copper, see Copper Associated Hepatopathy.
• Discontinue exposure to suspected causal 
xenobiotics, raw diets, rawhide products, jerky 
treats, or other consumables from foreign 
countries lacking enforced surveillance policies 
for pet care product manufacture.
• Depends on cause; see specific chapters for 
infectious disorders.• Immunomodulation—if immune-mediated 
injury suspected with negative survey for 
infectious etiology; some injuries may 
transform to immune-mediated process.
• Idiopathic disease—glucocorticoids 
combined with azathioprine or myco -
phenolate or cyclosporin.
• Vomiting—antiemetics (e.g., metoclo -
pramide 0.2–0.5 mg/kg PO/SC q6–8h; 
ondansetron 0.5–1.0 mg/kg 30 min before 
feeding q12–24h); or maropitant 1.0 mg/kg 
SC/PO.
• Gastrointestinal bleeding—omeprazole 
1.0 mg/kg PO q12–24h or pantoprazole; 
sucralfate for gastroesophageal protection.
• Consider potential drug interactions 
because of broad spectrum of possible 
• Consider adjusting drugs requiring hepatic 
activation, biotransformation, or elimination.
• Immunosuppression—may worsen clinical 
signs if cause is infectious disorder.
  FOLLOW-UP
• Routine monitoring of supportive care in 
hospital—fluids, acid-base and electrolyte 
balance, and general response to inter -
ventional medications.
• Sequential hematologic, biochemical, 
imaging, and relevant serologic titer/PCR 
evaluations.
• Sequential physical assessments and 
clinicopathologic monitoring especially 
important with immunomodulation 
because infectious causes may have been 
overlooked.
• Chronic hepatitis, hepatic fibrosis, cirrhosis.
• Hepatic failure.
• Coagulopathy.
• Dissemination of undiagnosed infectious 
cause.
Depend on primary cause.  MISCELLANEOUS
• Brucellosis, mycobacterial, leptospirosis 
infections—concern for zoonotic potential.
• Blastomycosis, coccidioidomycosis, 
bartonellosis, leishmaniosis, toxoplasmosis—
not directly contagious but pet may serve as 
environmental exposure sentinel.
SEE ALSO
• Leishmaniosis.
• Mycobacterial Infections.
Chapman BL, Hendrick MJ, Washabau RJ. 
Granulomatous hepatitis in dogs: nine cases 
(1987–1990). J Am Vet Med Assoc 1993, 
203:680.
Hutchins RG, Breitschwerdt EB, Cullen JM, 
et al. Limited yield of diagnoses of 
intrahepatic infectious causes of canine 
granulomatous hepatitis from archival liver 
tissue. J Vet Diagn Invest 2012, 
24:888–894.
Macho LP , Center SA, Randolph JF , et al. 
Clinical, clinicopathologic, and hepatic 
histologic features associated with probable 
ketoconazole drug-induced liver injury in 
dogs: 15 cases (2015–2018). J Am Vet 
Med Assoc 2020 256(11):1245–1256.
Consulting Editor  Kate Holan(continued)  Hepatitis, Granulomatous

H628  Blackwell’s Five-Minute Veterinary Consult  
HHepatitis, Infectious (Viral) Canine
  BASICS
OVERVIEW
• Viral disease of dogs ( Canidae ) caused by 
canine adenovirus-1 (CAV-1). It is serologi-
cally homogeneous and antigenically distinct 
from respiratory CAV-2, the causative agent 
of canine infectious laryngotracheitis.
• CAV-1 has worldwide geographic distribu -
tion and it also causes disease in wolves, 
coyotes, skunks, and bears. It causes encepha -
litis in foxes.
• Virus is spread via direct dog-to-dog 
oronasal contact or via contact of 
contaminated fomites. Airborne transmission 
is not an important means of contracting the 
virus.
• Virus initially replicates in tonsils, then 
spreads to regional lymph nodes and 
bloodstream via lymphatics.
• Infection—targets parenchymal organs 
(especially liver), eyes, endothelium, lung, 
spleen, kidneys, and brain.
• Oronasal exposure—viremia (4–8 days); 
virus shed in saliva and feces; initial dispersal 
to hepatic macrophages (hepatic Kupffer 
cells) and endothelium; replicates in Kupffer 
cells; damages adjacent hepatocytes producing 
massive viremia when released.
• Adequate antibody response clears organs in 
10–14 days; virus can persist in renal tubules, 
glomeruli, iris, ciliary body, and cornea. Virus 
can be shed in urine for 6–9 months.
• Chronic hepatitis—after infection in dogs 
with only partial neutralizing antibody 
response.
• Cytotoxic ocular injury—anterior uveitis; 
leads to classic “hepatitis blue eye” and can 
cause glaucoma. Develops in ~1% of dogs 
after modified live virus (MLV) vaccine.
• Glomerulonephritis can develop 1–2 weeks 
after acute signs resolve and produce 
proteinuria and interstitial nephritis; chronic 
renal failure has not been described.
• Dogs and other Canidae .
• Most common in dogs <1 year of age.
• Any dog not vaccinated is susceptible.
SIGNS
• Depend on immunologic status of host and 
degree of initial cytotoxic injury.
• Peracute—fever; CNS signs; vascular 
collapse; disseminated intravascular coagula-
tion (DIC); death within hours.
• Acute—fever; anorexia; lethargy; vomiting; 
diarrhea; hepatomegaly; abdominal pain; 
abdominal effusion; vasculitis (petechia, 
bruising); DIC; lymphadenopathy; rarely, 
nonsuppurative encephalitis.
• Uncomplicated—lethargy; anorexia; 
transient fever; tonsillitis; vomiting; diarrhea; lymphadenopathy; hepatomegaly; 
• Late—20% of cases develop anterior 
uveitis and corneal edema 4–6 days post 
infection; recover within 21 days; may 
progress to glaucoma and corneal ulcera -
tion. May be the only clinical feature of 
inapparent infection.
• CAV-1.
• Unvaccinated dogs susceptible.
  DIAGNOSIS
• Canine herpesvirus (neonatal).
• Other infectious hepatopathies.
• Granulomatous hepatitis.
• Toxic hepatitis.
• Fulminant infectious disease—e.g., 
parvovirus, canine distemper.
• CBC—schistocytes; leukopenia during 
acute viremia, followed by leukocytosis with 
reactive lymphocytosis and nucleated red 
blood cells (RBCs); thrombocytopenia.
• Biochemistry—liver enzyme activity high 
initially, begins to decline within 14 days; low 
glucose and albumin reflect fulminant hepatic 
failure, vasculitis, and endotoxemia; low 
sodium and potassium levels reflect GI losses; 
hyperbilirubinemia if survive several days.
• Urinalysis—proteinuria (glomerular 
injury); granular casts (renal tubule damage); 
bilirubinuria consistent with jaundice.
• Coagulation tests—reflect severity of liver 
injury and DIC.
• Serology for antibodies to CAV-1—fourfold 
rise in immunoglobulin IgM and IgG; recent 
vaccine-induced antibodies confuse 
• PCR—real-time PCR not currently 
available; conventional PCR is able to 
differentiate between virulent CAV-1 and 
vaccine virus, which is CAV-2 in all current 
vaccines. Nasal, rectal, or ocular swabs or 
blood can be submitted as well as tissue at 
necropsy; positive results from urine can be 
difficult to interpret due to potential 
shedding from asymptomatic dogs.
• Viral isolation—anterior segment of eye, 
kidney, tonsil, and urine; difficult in 
parenchymal organs (especially liver) unless 
first week of infection.
IMAGING
liver; poor detail due to effusion.
observe hepatomegaly, hypoechoic  parenchyma (multifocal or diffuse pattern), 
and effusion.
• Liver cytology via aspiration or biopsy may 
identify intranuclear hepatocyte inclusions.
• Viral culture.
• Acute and convalescent serology.
• Necropsy.
• Acute—edema and hemorrhage of lymph 
nodes; serosal visceral hemorrhages; liver 
large, dark-mottled; edematous gallbladder; 
fibrinous exudate on liver, gallbladder, and 
other viscera; splenomegaly; renal infarcts; 
abdominal effusion. Perivascular necrosis in 
liver and other organs; widespread centrilobu-
lar to panlobular necrosis. Liver is discolored; 
abdominal effusion also observed in canine 
herpesvirus in neonates.
• Chronic—small, fibrotic or cirrhotic liver.
  TREATMENT
• Usually inpatient.
• Fluid therapy—balanced polyionic fluids; 
avoid lactate if fulminant hepatic failure; 
carefully monitor fluids to avoid 
overhydration in context of increased vascular 
permeability.
• Judicious potassium (and other 
electrolyte) supplementation since 
electrolyte depletion may augment hepatic 
• Avoid neuroglycopenia—supplement fluids 
with dextrose (2.5–5.0%) as necessary.
• Blood component therapy for 
coagulopathy; blood component preferred to 
synthetic colloids for support of colloidal 
osmotic pressure; widespread vasculitis and 
DIC allow rapid systemic third-space colloid 
dispersal.
• Overt DIC—fresh blood products and low 
molecular weight heparin, e.g., enoxaparin 
100 U/kg (1 mg/kg) q24h. See Coagulopathy 
of Liver Disease.
• Nutritional support—frequent small 
meals as tolerated; optimize nitrogen 
intake; inappropriate protein restriction 
may impair tissue repair and regeneration; 
nitrogen restriction advised only if overt 
signs of HE. A feeding tube may be 
necessary initially.
• If oral feeding not tolerated, provide partial 
parenteral nutrition (maximum 5 days) or, 
preferably, total parenteral nutrition.
• Prophylactic antimicrobials—transmural 
passage of enteric bacteria and endotoxemia

Canine and Feline, Seventh Edition  629
HHwith hepatic failure; e.g., ticarcillin 
(33–50 mg/kg q6–8h) combined with 
metronidazole (reduce conventional 
dose to 7.5 mg/kg IV q8–12h) and 
fluoroquinolone.
• Antiemetics—metoclopramide (0.2–0.5 mg/
kg PO/SC q6–8h or CRI); ondansetron 
(0.5–1.0 mg/kg PO q12h); maropitant (1 mg/
kg/day SC).
• Gastroprotection—proton pump inhibitors 
(omeprazole 0.5–1.0 mg/kg PO q12–24h, 
pantoprazole 0.7–1.0 mg/kg IV q12–24h); 
H2 receptor antagonists (e.g., famotidine 
0.5 mg/kg PO/IV/SC q12–24h) and 
• Manage HE (see Hepatic Encephalopathy).
• Ursodeoxycholic acid—choleretic and 
hepatoprotectant (10–15 mg/kg daily in two 
divided doses, with food); give indefinitely if 
chronic hepatitis.
• Antioxidants—vitamin E (10 IU/kg/day 
PO), N-acetylcysteine IV (140 mg/kg load, 
then 70 mg/kg q8h) until PO route possible; 
transition to S-adenosylmethionine (20 mg/
kg/day PO, dose on empty stomach) when 
patient can tolerate oral medications until 
liver enzymes normalize or indefinitely if 
• Consider severity of liver injury, protein 
depletion, and age in calculating drug 
dosages.
• Sucralfate may impair oral absorption of 
certain medications (fluoroquinolones, 
tetracycline, doxycycline, and fat-soluble 
vitamins, e.g., vitamin E).  FOLLOW-UP
• Monitor fluid, electrolyte, acid-base, and 
coagulation status to adjust supportive 
measures.
• Monitor for acute renal failure.
MLV vaccination—at 6–8 weeks of age; two 
boosters 3–4 weeks apart until 16 weeks of 
age; booster at 1 year; highly effective vaccine; 
boosters may not be needed.
• HE.
• DIC.
• Chronic hepatitis.
• Peracute—poor prognosis; death within 
hours.
• Acute—variable: guarded to good prognosis.
• Poor antibody response (titer 
1 : 16–1 : 50)— chronic hepatitis may 
develop.
• Good antibody response (titer >1 : 500 
IgG)—complete recovery in 5–7 days 
possible.
• Recovered patients—may develop chronic 
liver or renal disease.  MISCELLANEOUS
• Maternal antibody—may protect some pups 
for first 8 weeks; depends on maternal antibody 
concentration and efficacy of passive transfer.
• Vaccination of pups with high levels of 
passively acquired antibodies—successful at 
14–16 weeks of age.
SEE ALSO
• CAV-1 = canine adenovirus-1.
• RBC = red blood cells.
Greene, CE. Infectious canine hepatitis and 
canine acidophil cell hepatitis. In: Greene 
CE, ed. Infectious Diseases of the Dog and 
Cat, 3rd ed. Philadelphia, PA: Saunders, 
2012, pp. 42–47.
Sharon A. Center.(continued)  Hepatitis, Infectious (Viral) Canine

630  Blackwell’s Five-Minute Veterinary Consult  
HHepatitis, Suppurative and Hepatic Abscess
  BASICS
OVERVIEW
• Bacterial infection involving the hepatobil­
iary system.
• Distribution and lobular involvement—
variable; multifocal microabscessation; diffuse 
suppurative cholangitis/cholangiohepatitis; 
cholecystitis; choledochitis, or discrete focal 
lesions; lesions associate with pyogenic 
bacteria.
• Large abscesses associated with hepato­
cellular carcinoma (HCA) in dogs.
• No breed predilection.
• Hepatic abscesses—most common: old 
dogs with HCA, or secondary to immuno­
suppression or diabetes mellitus; in neonates 
subsequent to omphalitis.
• Suppurative septic cholangitis/cholangio­
hepatitis—most common in young to 
middle ­aged male cats.
• Cholestatic disorders predispose to enteric 
bacterial translocation and impair canalicular 
bacterial egress from the liver.
SIGNS
• Gastrointestinal signs—vomiting, diarrhea.
• T rembling.
• Fever.
• May become jaundiced.
• Fever or hypothermia (cats).
• Abdominal pain—cranial abdomen.
• Hepatomegaly—focal, with large abscess or 
mass.
• Effusion—abdominal distention or fluid wave.
• May develop jaundice.
• Endotoxemia—tachycardia, tachypnea, 
hypotension, hypoglycemic collapse.
• Hematogenous infection via the portal vein, 
hepatic artery, or umbilical vein.
• Biliary tree obstruction, preexisting 
hepatobiliary or pancreatic disease, and 
• Ascending biliary tract infection.
• Cholecystoenterostomy.
• HCA with necrotic foci.
• Compromised immune responses: diabetes 
mellitus, glucocorticoid administration, 
hyperadrenocorticism, hypothyroidism, 
chemotherapy, immune ­mediated disorders 
managed with immunosuppressives.• Recurrent urinary tract infections; 
pyelonephritis.
• Penetrating wounds.
• Complication of hepatic biopsy or other 
surgery.
  DIAGNOSIS
• Infectious or necroinflammatory disease.
• Pancreatitis or pancreatic abscess.
• Hepatobiliary neoplasia.
• Hematoma.
• Metastatic neoplasia.
• Biliary cystadenoma.
• Gastrointestinal obstruction or perforation.
• Peritonitis, other intra ­abdominal abscess.
• Cholecystitis, choledochitis, cholelithiasis.
• CBC—neutrophilic leukocytosis with left 
shift and toxic white blood cell (WBC) 
changes; monocytosis; thrombocytopenia; 
nonregenerative anemia, schistocytes (dissemi ­
nated intravascular coagulation [DIC]).
• Biochemistry—variably increased alanine 
aminotransferase (ALT) > alkaline phosphatase 
(ALP) activity, increased aspartate aminotrans ­
ferase (AST), hypoglobulinemia, hyperglobu ­
linemia, inconsistent hyperbilirubinemia and 
hypoglycemia, inconsistent hypocalcemia (cats).
• Urinalysis—usually normal; bilirubinuria; 
• Serum bile acids—normal or high.
• Coagulation tests: changes consistent with 
DIC.
• Urine culture may or may not disclose 
hematogenously dispersed organisms.
IMAGING
• Hepatomegaly; irregular or rounded liver 
margins: diffuse or single lobe if isolated abscess.
• Hepatic mass effect.
• Reduced abdominal detail—effusion or 
• Gas pattern in hepatic parenchyma or 
biliary tree.
• Thoracic radiographs—normal, or 
consistent with pneumonia or chronic 
bronchitis.
• Best noninvasive method of abscess 
detection ( >0.5 cm lesions); solitary, variably 
echogenic, cavitated, hyperechoic rim.
• Dystrophic tissue mineralization or 
entrapped gas.
• Highly echogenic interface with cavitated 
mass—may be gas; combination with an 
abdominal effusion and hyperechoic 
perilesional effect supports an abscess.
• Multiple masses, may be complex.• Miliary abscesses—cannot discern from 
other parenchymal hepatic disorders.
hepatitis syndrome (CCHS)—image not 
unique from nonsuppurative CCHS.
• Inconsistent regional lymphadenopathy.
Cytology
• Cytology is essential; histologic specimens 
may not reveal bacterial organisms.
• Samples—effusion; hepatic parenchyma, 
discrete lesions; cholecystocentesis: transhe­
patic approach, liquid bile and biliary debris.
• Stains—Wright ­Giemsa for bacterial 
detection; Gram stain for morphology.
• Look for bacteria within biliary debris, in 
WBCs; primary or predisposing disease (e.g., 
neoplasia, VH reflecting adrenal disease or 
diabetes mellitus).
Culture and Sensitivity Testing
• If suppurative or pyogranulomatous—culture 
for aerobic, anaerobic bacteria, fungal organisms.
• Blood—aerobic and anaerobic culture.
• Polymicrobial infections ~30%.
  TREATMENT
• Inpatient—if signs of sepsis.
• IV fluids and antibiotics—essential.
• Fluid support—correct dehydration; rectify 
acid­base and electrolyte disturbances.
• Abscess—drain via lobectomy during 
laparotomy or under ultrasound guidance 
before surgery; if endotoxic shock, ultrasound 
facilitated drainage is best; after drainage, 
monitor body temperature, liver enzymes, 
WBC count, and sequentially image with 
ultrasound (monitor abscess size, focal or 
diffuse peritonitis); judiciously repeat 
drainage (may require insertion of an 
indwelling catheter for short ­term continuous 
drainage); consider alcoholization of abscess 
after drainage.
• In middle ­aged/older dogs—lobectomy for 
abscess removal and possible wide ­margin 
resection of an HCA.
• If extrahepatic bile duct obstruction 
(EHBDO)—see Bile Duct Obstruction 
(Extrahepatic).
• Antibiotics—initially based on cytology 
and Gram stain, then adjusted based on 
culture and sensitivity results; continue for 
2–4 months, perhaps longer.
• Initial treatment—combine antimicrobials 
for possible polymicrobial infection; common 
effective empirical combination includes

Canine and Feline, Seventh Edition  631
Hticarcillin (25–50 mg/kg over 15 min CRI) 
or amoxicillin clavulanate (13.75–20 mg/kg 
PO q12h), enrofloxacin (5–10 mg/kg PO/IV/
SC q12h in dogs or cats), and metronidazole 
(15 mg/kg IV q12h; reduce dose by 50% if 
hepatic dysfunction or severe cholestasis) or 
clindamycin (10–16 mg/kg SC per day; 
reduce dose if hepatic dysfunction or severe 
cholestasis to 5 mg/kg SC per day).
• Choleretics advised if biliary tree involved, 
but if EHBDO not until  biliary 
decompression; see Bile Duct Obstruction 
(Extrahepatic); Cholangitis/Cholangiohepatitis 
Syndrome.
• Antioxidants advised (see Hepatitis, Chronic).
• Aminoglycosides—do not use until normal 
• Avoid drugs metabolized or excreted by the 
liver or those known to be hepatotoxic if 
compromised liver function; adjust dosages or 
frequency of drugs if suspect reduced hepatic 
elimination, cholestasis, or hepatic 
  FOLLOW-UP
• Assess vital signs, labwork abnormalities, 
and physical condition.• Sequential ultrasound examinations—mon­
itor for abscess recrudescence or suppurative 
• If percutaneous drainage and alcoholization 
of an abscess—ultrasound monitoring at 
24 and 48 hours post procedure and 15, 30, 
60, and 120 days is recommended.
• DIC.
• Septic peritonitis.
• Favorable prognosis—early detection and 
aggressive antimicrobial treatment, with 
judicious surgical intervention.
• Guarded prognosis—concurrent disorders, 
especially hepatic neoplasia.
syndrome.
coagulation.• EHBDO = extrahepatic bile duct 
• HCA = hepatocellular carcinoma.
Schwarz LA, Penninck DG, Leveille ­Webster 
C. Hepatic abscesses in 13 dogs: a review of 
the ultrasonographic findings, clinical data, 
and therapeutic options. Vet Radiol 
Ultrasound 1998, 39:357–365.
Sergeeff JS, Armstrong PJ, Bunch SE. 
Hepatic abscesses in cats: 14 cases 
(1985–2002). J Vet Intern Med 2004, 
18:295–300.
Zatelli A, Bonfanti U, Zini E, et al. 
Percutaneous drainage and alcoholization 
of hepatic abscesses in five dogs and a cat. 
J Am Anim Hosp Assoc 2005, 41:34–38.
Author  Ashleigh Seigneur
Sharon A. Center.(continued)  Hepatitis, Suppurative and Hepatic Abscess

632  Blackwell’s Five-Minute Veterinary Consult  
HHepatocellular Adenoma
  BASICS
OVERVIEW
• A benign liver tumor of epithelial origin.
• May be more common than primary 
malignant liver tumors.
• Rare in dog and very rare in cat.
• Affected dogs commonly >10 years of age.
• Breed predispositions unknown.
SIGNS
• Usually asymptomatic; when clinical signs 
present, symptoms may be nonspecific; 
typically incidental finding.
• Acute tumor rupture may cause hemoperi-
toneum with resultant weakness and 
hypovolemic shock-like symptoms.
• Occasionally, large tumors may cause cranial 
abdominal pain, vomiting, and inappetance.
Definitive cause or risk factors for tumor 
development are unknown.
  DIAGNOSIS
• Hepatocellular carcinoma.
• Hepatic nodular hyperplasia.
• Abdominal mass.
CBC
• Anemia—regenerative anemia if tumor is 
bleeding, or anemia of chronic disease.
• Leukocytosis with a left shift—large tumors 
with necrotic centers (rare).
• Liver enzymes variable.
• Serum total bilirubin values—usually normal.
Unremarkable
• Serum bile acids are usually normal unless 
tumor growth compromises hepatic perfusion 
and biliary flow.
• Coagulation abnormalities consistent with 
occur rarely with large necrotic or hemorrhagic 
tumors.
IMAGING
• May demonstrate a single mass lesion or 
apparent asymmetry of hepatic silhouette.
• Rarely, gas in necrotic center of tumor.Abdominal Ultrasonography
May identify discrete mass effect with variable 
echogenicity, ranging from normal liver 
echogenicity to mixed echogenicity, presence 
of multiple nodules, or cystic mass appearance.
• May allow for improved assessment 
regarding surgical feasibility, especially for 
large tumors, or tumors associated with 
critical structures, such as the gallbladder.
• May detect additional lesions, depending 
on the contrast enhancement protocol.
• Hepatic aspiration cytology with ultrasono-
graphic guidance may allow the identification 
of normal hepatocytes or cells with mild 
atypia; this diagnostic will not be useful to 
differentiate between benign and low-grade 
malignant hepatic tumors, but will be useful 
to exclude other neoplastic diseases.
• Hepatic biopsy with T ru-Cut® needle—sev-
eral core biopsies are necessary to provide 
enough tissue for histopathologic characteri-
zation; due to the overlap between the 
hepatocellular adenoma and the low-grade 
hepatocellular carcinoma, it may be difficult 
• Abdominal exploratory surgery followed by 
mass resection (liver lobectomy) and histo -
pathology is the best way to obtain a definitive 
diagnosis and treat the disease.
• Usually well-circumscribed single nodules 
<10 cm in diameter.
• May be yellow-brown.
• Often soft, highly vascular, and friable.
• Occasionally multiple.
• Occasionally very large ( >20 cm).
Microscopic Findings
• May be difficult to distinguish from 
nodular hyperplasia, normal liver tissue, or 
low-grade hepatocellular carcinoma.
• Usually well-defined trabecular pattern; not 
necessarily encapsulated.
• Compression of adjacent hepatic parenchyma 
common.
• Mitotic figures infrequent.
  TREATMENT
• Surgical resection for large tumors, or 
tumors that cause clinical signs or organ 
• Bleeding tumor—requires immediate 
emergency care: hemodynamic stabilization, 
blood transfusion, and exploratory surgery.
• Excision recommended for large, single-
mass lesions.• Between 60% and 70% of the liver can be 
resected if the patient is healthy, and 
appropriate postoperative supportive care is 
• Biopsy of local lymph nodes, normal-
appearing liver, and any abnormal tissue 
identified during the exploratory surgery is of 
paramount importance.
None
  FOLLOW-UP
• Liver enzymes—serial evaluation, 
especially if they were elevated at the time 
of diagnosis.
• Abdominal ultrasonography— every 3–4 
months for the first year; preferred method of 
reevaluation.
Risk of tumor necrosis and massive 
abdominal hemorrhage if not resected.
Excellent
SYNONYMS
Hepatoma—should be avoided; refers to 
hepatocellular carcinoma in human medicine 
and hepatocellular adenoma in veterinary 
medicine.
SEE ALSO
Hepatocellular Carcinoma
Cave TA, Johnson V, Beths T, et al. T reatment 
of unresectable hepatocellular adenoma in 
dogs with transarterial iodized oil and 
chemotherapy with and without an embolic 
agent: a report of two cases. J Vet Comp 
Oncol 2004, 1:191–199.
Warren-Smith CM, Andrew S, Mantis P , 
Lamb CR. Lack of associations between 
ultrasonographic appearance of 
parenchymal lesions of the canine liver and 
histological diagnosis. J Small Anim Pract 
2012, 53(3):168–173.

Canine and Feline, Seventh Edition  633
HHepatocellular Carcinoma
  BASICS
OVERVIEW
• Malignant epithelial liver tumor. 
• Accounts for about 50% of malignant 
hepatic tumors. • Metastasis to regional 
lymph nodes, lungs, and peritoneal cavity in 
dogs is associated with the nodular and 
diffuse forms of hepatocellular carcinoma.
• Uncommon in dogs and rare in cats. 
• Affected dogs commonly >10 years of age. 
• No breed predispositions, although golden 
retrievers, miniature schnauzers, and male 
dogs are overrepresented in some studies.
SIGNS
• Typically absent until disease is advanced, 
unless it causes biliary obstruction. • Many 
times incidental finding. • Lethargy.
• Weakness. • Anorexia. • Weight loss. 
• Polydipsia. • Diarrhea. • Vomiting. 
• Hepatomegaly (asymmetric)—consistent; 
precedes development of overt clinical signs. 
• Unknown. • May be associated with 
chronic inflammation or hepatotoxicity.
  DIAGNOSIS
• Hepatic adenoma. • Nodular hyperplasia. 
• Biliary cystadenoma. • Bile duct adenoma/
carcinoma. • Metastatic neoplasia. • Polycystic 
liver disease—less common form; fibrous 
stroma hyperplasia with anaplastic duct cells; 
few cysts. • Hepatic lymphoma, hemangio-
sarcoma, carcinoid.
CBC
• Usually unremarkable. • Anemia in >50% 
of cases with massive hepatocellular carci-
noma in one study. • Anemia may be 
regenerative if tumor is bleeding. • Leukocytosis 
with a left shift—tumors with necrotic 
centers.
• Liver enzymes variable. • Serum total 
bilirubin values—usually normal. • May note 
hypoalbuminemia, hypoglycemia, and 
• Serum bile acids—normal unless tumor 
impairs hepatic perfusion and biliary flow. 
• Coagulation parameters— consistent with disseminated intravascular coagulation (DIC) 
in patients with massive or necrotic tumors, 
or intra-abdominal bleeding.
IMAGING
• May demonstrate a single-mass lesion, 
apparent asymmetry of hepatic silhouette, or 
hepatomegaly. • Rarely, gas in necrotic center 
of tumor. • Loss of serosal detail in case of 
hemoabdomen.
• Discrete mass lesion with variable echo-
genicity, depending on the presence of 
intratumoral necrosis, hemorrhage, gas, or 
cystic cavities. • Massive enlargement of a 
single liver lobe is occasionally observed. 
• Mixed echogenic pattern—most common. 
• Nodular pattern of lesions.
CT/MRI
CT is indicated for surgical planning 
(determine divisional or lobar origin), or 
when tumor involves/close proximity to 
critical anatomic structures, such as major 
vessels and the bile duct.
• Aspiration cytology—to exclude other types 
of neoplasia (lymphoma, sarcoma, etc.); 
aspirate cytology cannot reliably differentiate 
between hepatocellular carcinoma and benign 
hepatocellular proliferation (adenoma, 
hyperplasia). • Surgical hepatic biopsy for 
confirmation. • If tumor is not surgically 
resectable, ultrasound-guided needle biopsy 
may be useful in obtaining definitive diagnosis.
• Three clinical subtypes of this tumor are 
described—massive, nodular, and diffuse. 
• Nodular forms account for 30% and diffuse 
types account for 10% of all reported 
hepatocellular carcinomas in dogs, and both 
types involve multiple liver lobes. • Massive 
form that is confined to one lobe accounts for 
about 60% of canine hepatocellular carci-
noma cases. • Presence of necrotic areas. 
• Diffusely infiltrated tumors may not be 
grossly apparent other than hepatomegaly.
  TREATMENT
• Complete excision (liver lobectomy) 
recommended when possible; excision with 
microscopically dirty margins can still afford 
durable tumor control and long survival 
times. • Massive form is often amenable to 
surgical resection. • Nodular and diffuse 
forms are often not amenable to surgery. • Between 60% and 70% of the liver lobes 
can be resected if the patient is healthy and is 
given appropriate postoperative care.
While toceranib administration has resulted 
in short-term tumor control for some dogs, 
no medical treatment options have been 
successful in reducing tumor recurrence or 
risk for metastasis.
  FOLLOW-UP
• Abdominal ultrasonography—2 weeks 
postoperative for baseline and every 3–4 
months for the first year. • Abdominal CT 
appears more sensitive than ultrasonography 
for detection of small, recurrent lesions. 
• Monitor liver enzymes serially.
Risk of tumor necrosis and massive abdomi-
nal hemorrhage if unresected.
PROGNOSIS
• Massive forms treated with surgery have a 
better prognosis than do the nodular or 
diffuse forms. • Median survival of dogs 
with massive form treated with surgery 
may be >1,460 days. • Local tumor 
recurrence or de novo tumor growth is not 
uncommon.
Polycystic liver disease in cats.
Goussev SA, Center SA, Randolph JF , et al. 
Clinical characteristics of hepatocellular 
carcinoma in 19 cats from a single 
institution (1980–2013). J Am Anim Hosp 
Assoc 2016, 52(1):36–41.
Liptak JM, Dernell WS, Withrow SJ. Liver 
tumors in cats and dogs. Compend Contin 
Educ Pract Vet 2004, 26:50–56.

H634  Blackwell’s Five-Minute Veterinary Consult  
HHepatocutaneous Syndrome
  BASICS
OVERVIEW
• Liver lesion—severe degenerative vacuolar 
hepatopathy, hepatocyte degeneration leads to 
parenchymal collapse associated with marked 
proliferative hepatocyte response; this process 
leads to severe hepatic nodularity; hepatocu-
taneous syndrome (HCS) hepatopathy often 
associated with syndromic pressure point 
crusting, painful dermatosis, and diabetes 
mellitus (DM).
• Liver lesions—may precede cutaneous 
lesions and DM.
• Hepatopathy—recognized on abdominal 
US, pursued because of marked alkaline 
phosphatase (ALP) increase.
• Occasionally HCS hepatopathy develops in 
dogs treated chronically with phenobarbital.
• Middle-aged to older dogs.
• Males may have a greater predilection.
• Familial syndrome in shih tzu dogs 
described.
SIGNS
• Acute to subacute onset; may be few initial 
signs.
• Common signs— anorexia, weight loss, 
lethargy, polyuria/polydipsia, diarrhea, 
vomiting, ± jaundice, often with prominent 
cutaneous pressure point and painful foot pad 
lesions characterized as fissured crusted 
oozing wounds.
• Lethargy, poor body condition, with foot 
pad and elbow lesions causing pain in 
standing and recumbent postures, may be 
jaundiced.
• Cutaneous lesions—see Superficial 
Necrolytic Dermatitis.
• Normal, small to large hepatic size.
• Rare abdominal effusion—signifies 
late-stage HCS hepatopathy.
• Etiology—associated with pathologic 
hypoaminoacidemia and aminoaciduria; low 
amino acid (AA) concentrations seemingly 
have causal association with cutaneous and 
liver lesions. Most significantly low AA 
affiliated with urea cycle and synthesis of 
glutathione and collagen.
• Hyperglucagonemia associated with 
glucagonoma—originally proposed as causal 
mechanism but that remains unproven; 
~30–40% of tested dogs have increased plasma 
glucagon concentrations; glucagonoma 
confirmed in <15% of reported cases.
• Insulin-resistant DM—commonly 
associated with HCS; may reflect increased 
glucagon.• Contributing role hypothesized for 
ill-defined deficiencies of zinc, fatty acids, 
or niacin.
• Similar cutaneous lesions described with 
primary hepatopathies caused by phenobarbi-
tal or rarely chronic mycotoxicosis.
  DIAGNOSIS
• Cirrhosis—unresolvable architectural 
remodeling with fibrosis, sinusoidal hyperten-
sion, and regenerative nodules.
• Chronic hepatitis—inflammatory infiltrates 
and individual hepatocyte necrosis.
• Copper associated hepatopathy—  pathologic 
copper accumulation initially with zone 3 
associated with oxidative necroinflammatory 
hepatocyte injury.
• Diffuse nodular hyperplasia—rare cause of 
hepatic nodularity of similar magnitude.
• Degenerative glycogen-type vacuolar 
hepatopathy (VH)—may evolve similar 
nodular hepatic US pattern.
• CBC—mild to moderate nonregenerative 
to mild regenerative anemia; red blood cell 
microcytosis; neutrophilic leukocytosis 
reflecting cutaneous lesion inflammation or 
• Biochemistry—high liver enzymes 
(especially ALP); variable hypoproteinemia 
with hypoalbuminemia, low cholesterol and 
blood urea nitrogen; euglycemic to fasting 
hyperglycemia.
reflects hepatic insufficiency in end-stage 
hepatopathy; occasionally develop acquired 
portosystemic shunts, with shunting 
contributing to hyperammonemia.
• Total serum bile acids—normal or 
increased.
• Insulin—inappropriately increased before 
development of diabetes mellitus.
• Plasma glucagon—inconsistently 
• Plasma AA profile—30–50% reduction in 
AA concentrations of healthy dogs; dogs with 
cutaneous lesions have more severe AA 
deficiencies than dogs with only HCS hepato-  
 pathy.
• Urine AA profile—prodigious renal wasting 
of lysine and proline; profile of urine AA 
concentrations must be normalized with urine 
creatinine concentration for interpretation.
IMAGING
• Abdominal radiography—variable liver size 
(small, normal, to large); rare effusion.
• Abdominal US—may disclose irregular 
liver margin; characteristic nodular pattern: 
hypoechoic foci (proliferative nodules) with background hyperechoic parenchyma 
(glycogen-type VH and lipid-type VH) 
typified as “Swiss cheese pattern”; although 
suggested as pathognomonic, other causes 
of severe degenerative VH also may 
demonstrate this pattern; occasional diffuse 
nodularity cannot be imaged in HCS; 
pancreatic mass <15% of dogs.
• Aspiration sampling—hepatocytes display 
glycogen- and lipid-type vacuolation.
• Liver biopsy—needle biopsy may compro-
mise definitive diagnosis due to limited 
sampling of distinctive proliferative hepato-
cyte foci between regions with massive 
degenerative VH; needle biopsy may be best 
option for dogs with extensive skin lesions; 
larger laparoscopic samples preferred; avoid 
laparotomy as dogs with cutaneous lesions 
may not promptly heal.
• Skin biopsy—see Superficial Necrolytic 
Dermatitis; usually diagnostic for HCS.
• AA profiles in plasma and urine with urine 
AA normalized using urine creatinine disclose 
profound reduction of plasma AA and severe 
aminoaciduria with prominent losses of lysine 
and proline.
• Glucagonomas often express somatostatin 
receptors; these might be identified using 
radioisotope somatostatin label; however, 
prohibitively expensive for most clients.
• If pancreatic mass discovered, should be 
resected, submitted for routine and special 
stains (request immunohistochemical stains 
for neuroendocrine neoplasia); like other 
islet cell tumors, glucagonomas may produce 
other hormones (see Suggested Reading). 
Note: positive immunohistochemical 
staining does not confirm pathologic 
hormone secretion.
  TREATMENT
• Diet—use high-quality/high-quantity 
protein, energy-dense diets; enteral or 
parenteral feeding may be required for some 
dogs at initial diagnosis.
• If hepatic encephalopathy (HE) observed— 
improve nitrogen tolerance with lactulose and 
metronidazole (see Hepatic Encephalopathy) 
and use liver-specific diet as baseline formula.
• Supplemental AA therapy is cornerstone of 
treatment—IV route superior to oral route.
• Oral AA supplementation—historically 
done with egg yolk (3–6 yolks per day) but 
not very effective; dietary supplementation 
with anabolic whey protein powder increases 
protein intake, but alone not very effective; 
oral treatment may lack efficacy due to 
reduced enteral AA uptake.
• IV AA infusion with IV lipid infusion—
most effective therapy (lesion resolution and 
survival).

Canine and Feline, Seventh Edition  635
HH• IV AA infusion—8.5–10% solution of 
crystalline AA (Aminosyn®); using 10% 
solution (100 mL delivers 10 g AA) dose: 
25 mL/kg bodyweight over 6–8h through 
peripheral vein.
• IV 20% Intralipid® (or generic 20% IV fat 
emulsion)—dose: 7 ml/kg bodyweight over 
6–8h; given concurrently with IV AA using 
Y-adaptor for combined infusions through 
one line; combined therapy achieves best 
response to date.
• IV infusion treatment interval—initially 
q7–10 days until evidence of improvement: 
skin easiest to appraise with photo documen-
tation and evidence of foot pad pain 
resolution; hepatic lesions require US imaging 
for assessment: these take months to improve; 
liver enzymes may be used to infer improve-
ment but do not normalize (remain vacillat-
ing). RBC microcytosis resolves with 
significant recovery. After initial strong 
response, frequency of IV AA and IV 
Intralipid determined based on dog’s physical 
and lesional status and trends in hematologic 
and biochemical profiles. Chronically 
managed patients typically receive IV 
infusions at 6-week intervals, titrated 
frequency achieved by gradually lengthening 
intervals between infusions while monitoring 
for relapse.
• Essential fatty acid supplementation—
omega-3 fatty acids; double normal dose.
• Metastatic pancreatic tumors secreting 
glucagon may be controlled with longacting 
somatostatin analogue (octreotide: 2–3.7  μg/
kg q6–12h); prohibitively expensive.
• Manage DM with insulin and judicious 
dose titration to response.
• Other supplements—see Medications.
• Insulin for DM management; may 
demonstrate insulin resistance.
• AA infusion and lipid infusions and diet—
see above.
• Cutaneous or nail bed infections—systemic 
antimicrobials or antifungals; germicidal baths.• Ketoconazole—for secondary yeast 
infection; anti-inflammatory and antipruritic 
effects: monitor liver enzymes for drug-
induced liver injury warranting drug 
• Zinc supplementation—2–4 mg/kg 
elemental zinc q24h; avoid zinc methionine 
if HE.
• Niacinamide—250–300 mg/dog q12h 
(500 mg for dogs >10 kg); watch for toxic 
effects; avoid extended-release form.
• Topical glucocorticoids—if unresponsive 
inflammatory skin lesions, after infection 
managed ( caution : systemic glucocorticoids 
may promote HE, enteric ulceration, 
infection, may complicate DM 
management).
daily, divided dose given with food; hepato-
protectant against bile acid mediated 
membrane injury.
• Antioxidants —vitamin E (10 IU/kg daily 
PO with food); S-adenosylmethionine 
(20 mg/kg PO daily, empty stomach) 
provides additional metabolic and hepatopro-
tective influences.
• If associated with phenobarbital, discon-
tinue this drug.
• HE induction—high-protein diet 
supplements and AA infusions.
• Toxic effects of ketoconazole and its 
interference with p450 drug metabolism.
• Toxic effects of niacinamide and zinc.
  FOLLOW-UP
• Weekly to monthly physical exam, CBC, 
biochemistry, and urinalysis to assess need for 
IV AA and lipid infusions and treatments for 
secondary infections.
• As needed for management of DM.
• With HCS, IV infusions may cause 
thrombophlebitis and risk for 
thromboembolism.• Ketoacidosis—uncommon.
• Hepatic encephalopathy.
• Sepsis—due to diabetes and skin lesions or 
IV catheter-related infections.
• Pain—from skin lesions may require 
analgesics.
• Liver and skin lesions often improve with 
IV infusions.
• Some dogs achieve cutaneous remission  
≥3 years with described therapies.
• Some dogs have unremitting HCS 
progression, necessitating euthanasia.
SYNONYMS
• Superficial necrolytic dermatitis.
• Necrolytic migratory erythema.
• Metabolic epidermal necrosis.
• Glucagonoma syndrome.
• AA = amino acids
• DM = diabetes mellitus
• HE = hepatic encephalopathy
• HCS = hepatocutaneous syndrome
• VH = vacuolar hepatopathy
Bach JF , Glasser SA. A case of necrolytic 
migratory erythema managed for 24 
months with intravenous amino acid and 
lipid infusions. Can Vet J 2013, 
54:873–875.
Hall-Fonte DL, Center SA, McDonough SP , 
et al. Hepatocutaneous syndrome in Shih 
Tzus: 31 cases (1996–2014). J Am Vet Med 
Assoc 2016, 248(7):802–813.
Oberkirchner U, Linder KE, Zadronzny L, 
et al. Successful treatment of canine 
necrolytic migratory erythema (superficial 
necrolytic dermatitis) due to metastatic 
glucagonoma with octreotide. Vet Dermatol 
2010, 21:510–516.
Authors  Sharon A. Center and John P . Loftus
Consulting Editor  Kate Holan(continued)  Hepatocutaneous Syndrome

H
636  Blackwell’s Five-Minute Veterinary Consult  
H  BASICS
Large liver detected on physical examination, 
abdominal radiography, US, or direct visuali  - 
zation.
• Liver size—influenced by hepatotropic 
factors produced by splanchnic viscera 
(insulin dominates); delivered in portal 
blood. • Enlargement may reflect sinusoidal 
capacitance (blood pooling), parenchymal or 
sinusoidal accumulation of cells or substrates, 
or storage products expanding hepatocytes.
Diffuse or Generalized
• Inflammatory—immune-mediated, 
infectious, pyogranulomatous hepatitis; 
classified by infiltrative cell type. • Lympho -
reticular hyperplasia—response to antigens or 
accelerated erythrocyte destruction. 
• Congestion—impaired drainage through 
hepatic vein (cardiac, pericardial, thrombotic, 
neoplastic causes); sinusoidal occlusion 
syndrome or Budd Chiari syndrome. 
• Infiltration—cellular (neoplastic: primary 
hepatocellular, metastatic); excessive glycogen, 
lipid, or, rarely, metabolic products (genetic 
diseases) expanding hepatocytes or space of 
Disse (amyloid). • Cystic lesions as observed 
in ductal plate malformations (DPMs). 
• Cholestasis—most commonly with 
rarely, intrahepatic cholestasis causing bile 
duct distention. • Extramedullary hemat -
opoiesis (EMH)—diffuse, severe, or obstruct -
ing perfusion.
Nodular, Focal, or Asymmetric Hepatic 
Enlargement
• Neoplasia—hepatocellular carcinoma 
(HCA), hemangiosarcoma, lymphoma, 
metastatic carcinoma, other. • Hemorrhage. 
• Infection or inflammation. • Hepatic 
nodular hyperplasia (uncommon cause). 
• Nodular regeneration (uncommonly 
associated with hepatomegaly). • Arteriovenous 
malformation—involved lobe larger than other 
lobes; other lobes atrophied. • Asymmetric 
regeneration after large-volume resection or 
panlobular necrosis. • Biliary cystic lesions 
(DPM). • Other DPM malformations—large 
liver lobes usually with some atretic liver lobes 
or even atretic gallbladder; proliferative-like 
biliary epithelium with fibrotic bridging 
portal trabeculae (congenital hepatic fibrosis: 
DPM phenotype). • Liver lobe torsion—
acute venous congestion.
• Gastrointestinal—gastric compression or 
displacement by large liver. • Peritoneal 
effusion—sinusoidal or postsinusoidal hepatic 
hypertension weeping lymph. • Pulmonary—reduced ventilatory space from diaphragmatic 
compression. • General/vague pain—stretching 
of liver capsule, compression of adjacent viscera.
• Dog and cat. • Old animals more commonly; 
younger if DPM related.
SIGNS
• Abdominal distention or palpable mass. 
• Abdominal discomfort—vague location. 
• Dogs—liver palpable beyond costal margin 
(normal liver palpable in some breeds). 
• Cats—liver palpable >1.5 cm beyond 
costal margin (normal liver palpable in some 
cats). • May be undetected in obese animals.
CAUSES
Inflammation
• Infectious or chronic (early) hepatitis. 
• Acute toxic hepatopathy. • Feline 
(CCHS). • EHBDO. • Lymphoreticular/
pyogranulomatous—immune-mediated disease 
(hemolytic anemia, hemophagocytic syndrome, 
systemic lupus erythematosus, idiopathic), 
infectious disorders. • Venous outflow 
obstruction—sinusoidal occlusion syndrome 
or Budd Chiari syndrome.
Congestive Hepatopathy
• Increased central venous pressure—right-
sided congestive heart failure: tricuspid valve 
disease; cardiomyopathy; congenital anomaly 
(cor triatriatum dexter); neoplasia; pericardial 
disease; heartworm disease; pulmonary 
hypertension; severe arrhythmias or bradycar-
dia reducing cardiac output. • Vena caval or 
hepatic vein occlusion—thrombosis; tumor 
invasion or extramural caval occlusion; 
heartworm vena cava syndrome; vena caval 
stenosis or congenital kink (rare); diaphrag-
matic hernia; vena caval or large hepatic vein 
thrombosis (Budd Chiari syndrome); 
intrahepatic hepatic vein occlusion (thrombi, 
neoplasia, centrilobular parenchymal collapse 
causing sinusoidal occlusion syndrome). 
• Sinusoidal occlusion syndrome—collapsed 
centrilobular parenchyma and/or damage to 
hepatic venules impairing circulatory egress; 
causes include xenobiotic or herbal toxicity 
(e.g., pyrrolizidine alkaloids), severe non-
steroidal inflammatory drug–induced injury, 
severe copper hepatopathy. • Liver lobe 
torsion (acute).
Infiltration
• Neoplasia. • Metabolic abnormalities—
amyloid; lipid (see Hepatic Lipidosis [cats]), 
glycogen (see Glycogen-Type Vacuolar 
Hepatopathy [dogs]); cats and dogs: diabetes 
mellitus (DM), hyperlipidemic syndromes; 
neonatal metabolic storage disorders. 
• Lymphohistiocytic/pyogranulomatous—infectious disease, immune response, antigen 
stimulation, neoplasia (histiocytic/dendritic 
cells: histiocytic sarcoma), hemophagocytic 
syndrome.
Extramedullary Hematopoiesis
Regenerative anemias—hemolytic (immune-
mediated, congenital, metabolic, infectious); 
oxidant injury; erythroparasitism; severe 
blood loss, bone marrow failure; idiopathic.
Neoplasia
• Infiltrative, diffuse, or large focal tumors—
primary or metastatic. • Primary hepatic—
lymphoma; massive HCA; cholangiocarcinoma 
(bile duct carcinoma ± EHBDO); hemangio -
sarcoma. • Metastatic—lymphosarcoma, 
hemangiosarcoma, histiocytic sarcoma, 
fibrosarcoma, leiomyoma/sarcoma, neuroen -
docrine, osteosarcoma, others.
Major Bile Duct Obstruction
• Pancreatitis; pancreatic neoplasia. • Neoplasms 
in porta hepatis—bile duct carcinoma, 
lymphoma. • Granuloma/fibrosis of common 
bile duct. • Inspissated bile syndrome, 
choledochal cyst (DPM phenotype), or 
gallbladder mucocele. • Cholelithiasis. 
• Proximal duodenitis; duodenal foreign body. 
• Fluke migration (cats).
Cystic Lesions
• Primary single hepatic or biliary cysts. 
• Acquired cysts within neoplastic masses. 
• DPM—may associate with renal cysts 
(common in Persian cats). • Biliary 
cystadenoma (cats; DPM phenotype). 
• Hepatic abscesses (cystic cavitation); 
hepatocellular carcinoma housing abscess. 
• Parasitic—echinococcus (hydatid cyst).
Other
• Drugs—corticosteroids (see Glycogen-Type 
Vacuolar Hepatopathy), phenobarbital (dogs). 
• Hepatic nodular hyperplasia (rare cause). 
• Acromegaly—cats.
• Cardiac disease. • Heartworm disease. 
• Neoplasia. • Primary hepatic disease—
inflammatory, neoplastic, cystic, or other 
DPM phenotypes. • Corticosteroids—
exogenous or endogenous. • Phenobarbital 
treatment. • Poorly controlled DM. 
• Anorexia in obese cats—hepatic lipidosis. 
• EHBDO. • Cystic malformations—
DPM. • Certain anemias—diffuse hepatic 
EMH.
  DIAGNOSIS
Similar Signs
Distinguish from other disorders causing 
visceromegaly (gastric, splenic), cranial abdominal 
masses, or effusions via radiography and US.Hepatomegaly

Canine and Feline, Seventh Edition  637
HDifferential Causes
• Cardiac disorders—heart murmur, weak 
femoral pulses, hepatojugular reflex, jugular 
distention and jugular pulses, muffled heart 
sounds, arrhythmias, cough, dyspnea/
tachypnea. • Symptomatic anemia—pallor ± 
jaundice; tachycardia; tachypnea; exercise 
intolerance; bounding pulses. • Parenchymal 
liver disease—lethargy, anorexia, vomiting, 
diarrhea, weight loss, variable liver enzymes ± 
jaundice, coagulopathies, polyuria/polydipsia 
(PU/PD), if advanced may see hepatic 
encephalopathy (HE) or ascites. • Glycogen-
type vacuolar hepatopathy (VH; dog)—signs 
of hyperadrenocorticism or adrenal hyperplasia 
or other chronic disease imposing stress; 
DM—persistent hyperglycemia; PU/PD, 
signs of underlying endocrinopathy. 
• Hepatic lipidosis—jaundice in obese 
hyporexic cat, poorly controlled DM (dog or 
cat); failure-to-thrive puppies or kittens; 
congenital lysosomal or glycogen storage 
CBC
• Identify anemia and cause; spherocytes 
(immune-mediated hemolytic anemia, 
microangiopathic anemia); schistocytes 
(vascular shearing-microangiopathic, vena cava 
syndrome, hemangiosarcoma, disseminated 
intravascular coagulation (DIC), Heinz bodies 
(oxidant injury); erythroparasitism ( Mycoplasma 
haemofelis  or haemominutum , Babesia ). 
• Circulating blast cells—myeloproliferative or 
lymphoproliferative disorders. • Nucleated red 
cells—EMH, splenic disease, regenerative 
anemia. • Macrocytosis and nonregenerative 
anemia—feline immunodeficiency virus (FIV), 
feline leukemia virus (FeLV), myelophthisis. 
• Thrombocytopenia—increased consumption, 
destruction, or reduced platelet production. 
• Thrombocytosis—neoplasia; inflammation; 
hyperadrenocorticism; splenic disease.
• Inflammatory hepatic disorders—usually 
high liver enzyme activity; variable hyper -
globulinemia, bilirubin, and albumin 
concentrations. • Reticuloendothelial 
hyperplasia—variable liver enzyme activity. 
• Primary hepatic neoplasia—moderate to 
marked increases in liver enzyme activity 
(alkaline phosphatase [ALP] and 
𝛾-glutamyltransferase [GGT] usually 
predominate with HCA, variable alanine 
aminotransferase [ALT]. • Metastatic 
neoplasia—variable liver enzymes; occasional 
high calcium or globulin. • Infiltrative 
disorders—minor liver enzyme change; 
variable bilirubin concentration. • Glycogen-
type VH (dogs)—markedly high ALP; high 
cholesterol ± triglycerides with increased 
glucocorticoids or sex steroids; DM—high ALP , cholesterol, hyperglycemia. • Hepatic 
lipidosis (cats)—high ALP , aspartate 
aminotransferase (AST), ALT; minor increase 
in GGT unless concurrent pancreatitis, 
CCHS, or EHBDO. • Storage diseases—
may display few abnormalities. • EHBDO—
markedly high ALP , GGT, other enzymes; 
high bilirubin and cholesterol. • Cystic 
lesions—normal, except with hepatic abscess 
(markedly high ALT and AST) or CCHS 
(high ALP , ALT, GGT, variable bilirubin); 
DPM often presents with suppurative 
CCHS. • Phenobarbital-associated—high 
liver enzymes (especially ALP in dogs). 
• Nodular hyperplasia—normal to moder -
ately high ALP , elderly dogs: rare cause of 
• FeLV and FIV testing—cats. • Buffy coat—  
circulating blasts with neoplasia or uncommon 
cell type observed. • Coagulation panel—DIC 
common with hemangiosarcoma or diffuse 
lymphoma; prolonged coagulation times 
common with EHBDO >5 days esp. in cats. 
• Total serum bile acids (TSBA)—high in 
diffuse disorders or EHBDO; redundant test if 
nonhemolytic jaundice . • Pituitary-adrenal axis 
testing (dogs)—see Glycogen-Type Vacuolar 
Hepatopathy; Hyperadrenocorticism (Cushing’s 
Syndrome)—Dogs. • Insulin-like growth 
factor-1 (IGF-1) in acromegalic cats; typically 
males with DM. • Heartworm testing—in 
endemic areas. • Fungal serology—in endemic 
areas. • Other serology—e.g., Rickettsial, 
Bartonella , Leishmania , Toxoplasmosis .
IMAGING
• Hepatomegaly—rounded margins 
extending beyond costal arch; caudal-dorsal 
gastric displacement; caudal displacement: 
cranial duodenal flexure, right kidney, 
transverse colon. • May suggest cause.
• Three views (lateral [right, left], dorsal-  
ventral)—metastasis, other disorders, cranial 
displacement of diaphragm, wide vena cava if 
passive congestion. • Cardiac, pulmonary, 
pericardial, and vena caval disorders usually need 
US imaging. • Sternal lymphadenopathy—
reflects abdominal inflammation or neoplasia. 
• Puppies, kittens, deep inspiration, and certain 
canine breeds—spurious hepatomegaly.
• Liver size and surface contour. • Diffuse 
enlargement with normal echogenicity—  
congestion; cellular infiltration (lymphoma); 
inflammation; EMH; reticuloendothelial 
hyperplasia, diffuse amyloid deposition 
expanding space of Disse. • Diffuse enlarge-
ment with hypoechoic parenchyma—normal 
variation; congestion, lymphoma, diffuse 
sarcoma; amyloidosis expanding space of Disse. • Diffuse enlargement with hyper-
echoic parenchymal (minor nodularity)—
lipid or glycogen; inflammation; fibrosis; 
lymphoma; DPM fibrotic bridging portal 
trabeculae. • Diffuse enlargement with 
hypoechoic nodules—neoplasia; abscess; 
degenerative glycogen-type VH (dog); HCS, 
cystic lesions (DPM). • Identify EHBDO. 
• Identify concurrent abdominal diseases— 
kidneys; intestines; lymph nodes; effusion; 
interrogation of porta hepatis for obstructions 
and lymphadenopathy. • Identify portal or 
vena caval thrombi. • Identify abdominal 
effusion—distribution and echogenic 
patterns. • Cannot distinguish benign from 
malignant disease.
ECG/Echocardiography
Characterize cardiac rhythm, structure, 
function, pulmonary pressure gradient.
• Procedure—22-G, 2.5–3.75 cm (1–1.5 in) 
needle; diffusely large liver directly aspirated 
without US; focal lesions aspirated under US 
guidance. • Cytology—may disclose infectious 
agents, vacuolar change, neoplasia, inflamma-
tion, or EMH; definitive diagnosis seldom 
confidently confirmed (false-positive and 
-negative results). • Hepatic biopsy—if US 
rules out EHBDO, cytology does not indicate 
septic inflammation or neoplasia, and no 
obvious diagnoses made; percutaneous 
ultrasound–guided T ru-Cut® needle biopsy 
for suspected neoplasia or amyloid (avoid if 
abscess or EHBDO possible); otherwise, best 
sampling with laparoscopic or surgical 
exploratory approaches. • Microbial 
culture—aerobic and anaerobic bacterial; 
fungal as appropriate. • Staining—H&E 
(routine); reticulin (architectural substruc-
tural remodeling, infiltration, compression), 
Masson’s trichrome (collagen deposition, 
amyloid detection); rhodanine (copper); 
periodic acid–Schiff (glycogen ± amylase 
predigestion); acid-fast stain (mycobacteria if 
granulomatous inflammation); Congo red 
(amyloid); Oil Red O (lipid, requires frozen 
section), infectious disease stains (see 
Hepatitis, Granulomatous). • Coagulation 
testing—before liver sampling, consider 
measurement of prothrombin time, activated 
partial thromboplastin time, fibrinogen, 
buccal mucosal bleeding time (BMBT); 
prediction of iatrogenic hemorrhage poor 
with bench tests; BMBT may be more 
relevant. • Abdominal effusion—cytology; 
protein content; culture; evaluate before tissue

protein content; culture; evaluate before tissue 
sampling. • Pericardiocentesis—if pericardial 
tamponade. • Cyst aspiration sampling—if 
possible infectious cause when plausible 
treatment might be recommended; risk for 
abdominal contamination if hepatic abscess.(continued)  Hepatomegaly

638  Blackwell’s Five-Minute Veterinary Consult  
• Outpatient—except cardiac/pericardial 
causes or hepatic failure. • General supportive 
goals—eliminate or manage inciting cause; 
prevent complications; palliate derangements 
reflecting hepatic failure. • Important 
derangements—dehydration and 
hypovolemia; HE; hypoglycemia; acid-base 
and electrolyte abnormalities; coagulopathies; 
enteric hemorrhage; sepsis; endotoxemia.
• Heart failure or ascites—impose sodium 
restriction: fluids and food ( <100 mg/100 kcal, 
<0.2% dry matter basis food), prescribe 
appropriate cardiac medications or diuretics. 
• Supplement potassium chloride if IV 
fluids—sliding scale (maintenance = 20 mEq/L 
fluid). • Supplement B-soluble vitamins in IV 
fluids. • If jaundiced—parenteral vitamin K 
before invasive procedures.
ACTIVITY
Restricted; initial cage rest in some disorders.
DIET
• Dietary protein—restrict only if evidence of 
HE. • Well-balanced, adequate energy, 
positive nitrogen balance essential; adequate 
vitamins and micronutrients for most 
disorders; fat restriction only if hypertriglyc-
eridemia or steatorrhea. • May need feeding 
tube (e.g., esophagostomy tube) in cats with 
HL (see Hepatic Lipidosis). • Sodium—
restrict if cardiac failure or ascites.
• T reatment depends on underlying cause. 
• Many causes life-threatening; some less 
serious and amenable to treatment. 
• Thorough diagnostic evaluations essential 
for determining definitive cause and 
interventions.SURGICAL CONSIDERATIONS
• Resection of primary or focal hepatic mass 
lesions (neoplasia, abscess,  compromising 
cyst)—biliary  decompression if EHBDO. 
• Pericardiectomy (thoracoscopic  procedure)—  
if effusion recurs after initial pericardiocentesis.
• Avoid hepatotoxic drugs. • Glycogen-type 
VH (dogs)—avoid glucocorticoids. • Hepatic 
lipidosis (cats)—avoid catabolism or drugs 
that promote it; avoid fasting.
  FOLLOW-UP
• Physical assessment and hepatic imaging—
reassess liver size. • CBC, biochemistry, 
TSBA—serial assessments of lab 
abnormalities and liver function; packed cell 
volume and reticulocyte count with anemia. 
• Thoracic radiography, ECG, and 
echocardiography—reassess status. 
• Pituitary-adrenal axis—adrenal disorders. 
• Adjust drug dosages according to status of 
liver function, body condition, and weight.
Many causes are life-threatening.
Certain infectious agents of concern.SEE ALSO
• Glycogen Storage Disease.
• Hepatitis, Granulomatous.
• Hepatitis, Suppurative and Hepatic Abscess.
• BMBT = buccal mucosal bleeding time. 
syndrome.
coagulation. 
• DM = diabetes mellitus. 
• DPM= ductal plate malformation. 
obstruction. 
• IGF-1 = Insulin-like growth factor-1.
• PU/PD= polyuria/polydipsia.
Consulting Editor  Kate HolanHepatomegaly  (continued)

Canine and Feline, Seventh Edition  639
HHepatoportal Microvascular Dysplasia
  BASICS
• Microvascular dysplasia (MVD) describes 
intrahepatic microscopic vascular 
 malformations diminishing intrahepatic 
perfusion within tertiary portal vein 
branches; this is accompanied by a 
 compensatory increase in hepatic arterial 
perfusion (hepatic arterial buffer response); 
MVD lacks macroscopic portosystemic 
shunting but genetically associates with 
congenital portosystemic vascular anomalies 
(PSVA, shunts) as an apparent complex 
polygenic autosomal syndrome.
• Occurs as an isolated malformation or 
associated with PSVA.
• Clinically distinct from severe intrahepatic 
portal vein atresia that causes formation of 
acquired portosystemic shunts (APSS).
• Histologic features—stereotypic histologic 
responses reflect portal venous hypoperfusion, 
of which MVD is one of many causes; often 
misdiagnosed as portal hypoplasia.
• Clinicopathologic hallmark—increased total 
serum bile acid (TSBA) concentrations in the 
absence of other abnormalities observed in 
PSVA or disorders associated with APSS.
• Coexistence of MVD with PSVA explains 
failure of TSBA to normalize after complete 
PSVA attenuation, and inability to fully 
attenuate PSVA (some dogs).
• Malformations impairing intrahepatic 
portal venous perfusion reduce hepatocyte 
exposure to splanchnic-derived hepatotropic 
factors—this leads to lobular atrophy and 
impairs expedient hepatocyte extraction of 
bile acids from the enterohepatic circulation.
• Compensatory hepatic arterial buffer 
response maintains liver viability.
• Absence of macroscopic portosystemic 
shunting explains absence of clinical signs—
there is no hepatic encephalopathy (HE) or 
ammonium biurate uroliths or crystalluria in 
dogs with MVD.
• Usually asymptomatic.
• May observe slow recovery from sedatives or 
anesthetics requiring first-pass hepatic 
extraction and apparent adverse drug reactions 
with other medications undergoing first-pass 
hepatic extraction or hepatic metabolism.
• If concurrent inflammatory bowel disease 
(IBD)—vacillating signs include vomiting, 
diarrhea, inappetence, increased liver enzymes 
(often alanine aminotransferase [ALT]).
GENETICS
• Compelling evidence supports 
 inheritance of PSVA/MVD as a complex 
polygenic autosomal trait in many small 
pure-breed dogs.• Unaffected parents may produce 
affected progeny due to polygenic 
• Prevalence of PSVA/MVD trait in small 
pure-breed dogs 30–80%—varies with breed.
• Genetic association of MVD and PSVA in 
kindreds of certain breeds confirms that MVD 
is most common—10–30 : 1 of MVD : PSVA.
Worldwide
Species
Dog
• Small-breed dogs.
• Commonly affected breeds—Yorkshire 
terriers, Maltese, Cairn terriers, Tibetan 
spaniels, shih tzu, Havanese, miniature 
schnauzers, pugs, papillon, Norfolk 
terriers, bichon frisé, West Highland 
white terriers.
• Not identified in large-breed dogs.
• Not identified in cats.
Age and Range
MVD bile acid testing best done at 4–6 
months of age; use paired TSBA tests (pre 
and 2h post meal); neonatal testing not 
advised.
SIGNS
• Asymptomatic—unremarkable history; 
occasional delayed anesthetic recovery or 
drug intolerance reported.
• MVD often recognized serendipitously 
during routine screening tests or diagnostics 
for nonhepatic health problems, or during 
TSBA testing in breeds with high PSVA/
MVD prevalence.
• Concurrent illnesses may complicate 
TSBA interpretation (e.g., gastrointestinal 
[GI] malabsorption or diarrhea may cause 
erroneously low TSBA values), cholestasis 
(causes high TSBA values).
Unremarkable.
CAUSES
Congenital inherited disorder.
Purebred small-dog breeds and mixes of these 
breeds.
  DIAGNOSIS
• PSVA—suspected in symptomatic young 
dog with increased TSBA or HE; however, 
20% of PSVA dogs are asymptomatic or 
minimally symptomatic.• Other causes of increased ALT or high 
TSBA values (e.g., GI disease, cholestasis).
• CBC—normal.
• Biochemistry—generally unremarkable; 
hepatic enzyme activities normal (expect high 
alkaline phosphatase in young patients due to 
bone growth); vacillating ALT if coexistent IBD 
or degenerative/inflammatory centrilobular 
hepatic lesion (dogs with eosinophilic IBD); 
mild hypoglobulinemia or hypoalbuminemia 
noted in ~50% of young dogs.
• Urinalysis—normal.
• Hyperammonemia not documented in dogs 
with MVD without severe portal atresia, 
PSVA, severe ductal plate malformation 
congenital hepatic fibrosis phenotype, 
arteriovenous malformation (fistula), or some 
other acquired liver disorder.
TSBA
• Paired pre- and post-meal TSBA—  
recommended diagnostic test; pre- and 
post-meal TSBA >25 μmol/L reflect 
abnormal liver function or perfusion in 
absence of cholestasis.
• No need to fast patient before meal-  
provoked enterohepatic bile acid challenge.
• Random single TSBA in normal reference 
range not reliable assessment.
• Paired samples essential to evaluate bile acid 
enterohepatic circulation.
• Important TSBA testing strategy—food-
initiated enterohepatic bile acid challenge 
essential; verify meal consumption; feed typical 
size meal; feed dog’s regular diet for testing.
• Approximately 15–20% of dogs and ~10% 
of cats have pre-meal TSBA > post-meal 
TSBA; this reflects individual differences in 
physiologic coordination of gallbladder 
contraction, and gastric and enteric transit 
rate relative to food intake; thus, do not  apply 
fasting TSBA reference ranges.
• “Shunting pattern”—common: higher 
post-meal TSBA; post-meal TSBA concentration 
usually 0.5- to 3-fold > pre-meal TSBA.
• Best assessments—young small breed dogs 
at 6 months; avoids serendipitous discovery of 
high TSBA when dog later presents for 
nonhepatic illnesses, when inappropriate 
testing may be pursued chasing abnormal 
TSBA values.
• Magnitude of increased TSBA—typically 
lower for MVD vs. PSVA; but wide overlapping 
of values invalidates utility of TSBA as 
standalone test to distinguish MVD from 
PSVA; however, TSBA values ≥200  μM/L 
usually associate with PSVA or APSS.
• Quantitative abnormal TSBA values cannot 
discriminate severity of MVD between dogs; 
sequential testing demonstrates vacillating 
abnormal values (reflects physiologic 
variables).
• Avoid qualitative TSBA tests.

640  Blackwell’s Five-Minute Veterinary Consult  
HProtein C
• Protein C reflects severity of portosystemic 
shunting in dogs; not valid for this use in 
cats.
• Generalities—MVD: protein C usually  
≥70%; symptomatic PSVA: protein C <70%; 
asymptomatic PSVA: protein C may be  ≥70% 
more common in portoazygous PSVA.
IMAGING
• Abdominal radiography—normal.
• Abdominal US—no macroscopic shunting 
vessel; liver size subjectively normal or slightly 
small.
• Mesenteric portovenography—subtle 
abnormalities of blunted small portal vein 
branches, protracted contrast “blush” in liver 
lobes; caution : PSVA may be overlooked if 
radiographic portography only completed in 
single recumbent posture; CT angiograms lack 
definition to display MVD hypoperfusion.
• Colorectal (CRS) or splenoportal 
scintigraphy—  normal or slightly increased 
shunt fraction in MVD; scintigraphy may 
reveal irregular distribution of isotope among 
liver lobes.
• Liver biopsy—sample several liver lobes (at 
least 3) as MVD does not uniformly affect 
liver lobes; avoid  sampling caudate lobe as 
this lobe receives perfusion from first portal 
vein branch and is often best-perfused liver 
lobe in dogs with PSVA or MVD; surgical 
wedge or laparoscopic biopsies recommended.
• US-guided needle biopsy—may not sample 
enough tissue for definitive diagnosis.
Gross
• Normal appearance and liver size.
• Some liver lobes comparatively small, 
coordinating with histologic severity of MVD.
• Cannot  discriminate MVD, PSVA, 
noncirrhotic portal hypertension (NCPH), or 
extrahepatic portal venous thromboembolism 
(TE)/occlusion without history, clinical 
findings, and imaging details; cannot  
conclude portal vein hypoplasia.
• Histologic evaluation—required for definitive 
diagnosis of portal venous  hypoperfusion but 
must be considered in context of clinical, 
clinicopathologic, and imaging details; rules out 
most acquired hepatobiliary disorders causing 
increased TSBA except portal TE and NCPH; 
histopathologic features of all disorders causing 
portal venous hypoperfusion are similar; 
impossible to differentiate MVD from PSVA 
based only on liver biopsies in most cases.
• MVD diagnosis confused by inappropriate 
terminology, where “portal hypoplasia” has 
been used to characterize histologic features 
of portal venous hypoperfusion; “hypoplasia” 
defines lack of development—impossible to 
ascertain from liver biopsy without clinical features and vascular imaging details; MVD 
one of many causes of portal venous 
hypoperfusion.
• Stereotypic histologic features of portal 
venous hypoperfusion:
 ◦Lobular atrophy—small hepatocytes, 
closely approximated portal tracts and 
centrilobular regions, increased appearance 
of miniaturized (or juvenile) portal tracts 
(tiny, too many, too close).
 ◦Increased number of binucleated 
hepatocytes in portal regions reflecting focal 
proliferative response induced by restricted 
portal venous perfusion (proven in 
experimental models).
 ◦Increased arteriolar profiles with thick 
muscular walls, occasional single orphaned 
arterioles in hepatic parenchyma—findings 
reflect physiologic compensatory hepatic 
arterial buffer response increasing perfusion 
to peribiliary arterial plexus (vasa vasorum 
for bile ducts and portal veins); serpiginous 
arteries reflect increased pressure and flow, 
angiogenic formation of new arterial twigs, 
and branching architecture of peribiliary 
arterial plexus.
 ◦Small nonperfused or absent portal vein 
silhouettes or vascular silhouettes with 
malformative sacculated profiles (see below).
 ◦Prominent perivenular smooth muscle 
“throttling apparatus” of hepatic veins/venules 
in dogs (influences transhepatic perfusion) 
hypothesized to reflect physiologic response 
to arterialized transhepatic perfusion.
 ◦Distended lymphatics—in portal tracts, 
adjacent to hepatic veins, and variably 
beneath liver capsule reflect increased 
ultralymph formation from arterialized 
sinusoidal perfusion.
 ◦Variable scattered lipogranulomas 
(coalesced foamy macrophages) inconsist-
ently associate with hemosiderin-iron 
aggregates, represent foci of historic 
parenchymal injury.
 ◦Some dogs display obscured hepatic vein 
profiles by perivenular aggregates of lipid 
engorged macrophages (lipogranulomas) ± 
variable nonsuppurative inflammation, 
obscuring, or shrouding of venular profiles 
coordinates; if concurrent PSVA these may 
be intolerant of complete ligation.
• MVD malformative features in small-breed 
dogs:
 ◦Maldevelopment of tertiary portal vein 
branches—inconsistent identification of 
portal veins, portal vein silhouettes with 
dilated, thin-walled unusual-appearing 
vessels consistent with inlet veins (direct 
sinusoidal-portal tract interconnections).
 ◦Malposition of hepatic venules adjacent 
to portal triads sharing supportive adventitia 
termed “fusion complexes.”
 ◦Randomly distributed, aberrant wide 
irregular hepatic sinusoids (microvascular 
malformation). ◦Disorganized centrilobular hepatic cords 
with malformative web-like reticulin 
substructure (reticulin staining).
 ◦Unusual longitudinal hepatic venule 
profiles—demonstrating prominent 
throttling muscle contraction in dog.
 ◦Variation in histologic features among 
hepatic lobes.
• Note: animals ≤4 months of age  demonstrate 
increased juvenile or small portal triads.
  TREATMENT
• Asymptomatic—requires no medical 
interventions except avoidance or dose 
reduction of drugs dependent on hepatic 
first-pass extraction.
• Do not need  ursodeoxycholic acid, 
S-adenosylmethionine (SAMe; unless 
chronically increased liver enzymes 
implicating oxidative injury), silibinin 
extracts (milk thistle), or dietary protein 
• Rarely, some dogs develop centrilobular 
(zone 3) hepatocyte degeneration that may 
lead to chronic progressive hepatopathy; 
diagnosis requires hepatic imaging and liver 
biopsy; may require management for hepatic 
insufficiency and ascites; more common in 
Maltese, shih tzu, bichon frisé, Yorkshire 
terriers; US imaging may disclose attenuated 
hepatic vein profiles.
• Confirmed MVD associated with nonsuppu -
rative zone 3 inflammation (especially involving 
eosinophils) and IBD—usually managed with 
low-dose dexamethasone (0.05 mg/kg PO 
q48–72h) rather than prednisone to avoid 
mineralocorticoid supplementation that may 
provoke ascites, hypoallergenic or hydrolyzed 
diet (protein restriction only if HE; usually no 
protein restriction in MVD), or Vivonex® HN, 
and low-dose metronidazole 7.5 mg/kg PO 
q12h; if low protein C or increased D-dimers 
confirmed, add mini-dose aspirin 0.5 mg/kg 
PO q12–24h or clopidogrel; must have liver 
biopsy  confirming need for glucocorticoid and 
anticoagulants.
DIET
Dogs with only MVD do not require 
protein-restricted diet.
• Parents with normal TSBA may produce 
progeny with MVD or PSVA; examination 
of TSBA in F1 and F2 progeny is only 
method of recognizing optimal breeding 
strategy.
• Counsel clients and breed enthusiasts that 
TSBA values cannot  grade severity of MVD.
• TSBA testing should be used to identify 
MVD in juvenile dogs (6 months of age) to 
avoid future diagnostic confusion as might Hepatoportal Microvascular Dysplasia   (continued)

Canine and Feline, Seventh Edition  641
Hoccur in adult dogs with nonhepatic 
illnesses.
• Protein C— should not be used  as screening 
test without TSBA to rule out PSVA.
SAMe when chronically elevated liver enzyme 
activity (esp. ALT) indicates oxidative injury.
Beware of adverse reactions to drugs reliant on 
hepatic first-pass extraction or metabolism.
  FOLLOW-UP
• Asymptomatic dogs—no specific  treatment/  
long-term follow-up has confirmed normal 
lifespan, no chronic illness, no progressive 
hepatic degeneration with exception noted 
above.
• Repeated TSBA tests not advised as values 
remain abnormal and fluctuate.
Specific recommendations to eliminate 
MVD from a particular genetic line or breed 
possible at present. Based on information 
from large pedigrees of multiple dog breeds, 
simply breeding unaffected parents does not 
eliminate MVD from kindred. In high-
incidence kindreds, important to remain 
vigilant for vaguely ill dogs that may have 
PSVA; surgical exploration can miss PSVA as 
can portovenography if only single 
recumbent position evaluated; rather, 
CT angiography considered imaging gold 
standard; CRS definitively detects 
hepatofugal circulation (portosystemic 
shunting) and provides quick yes/no test to detect portosystemic shunting; protein 
C activity assists in differentiating dogs with 
PSVA from MVD to advise further 
expensive imaging, but is not definitive 
as standalone test.
• Most dogs with MVD remain asympto-
matic and have normal lifespan.
• Progressive increase in magnitude of TSBA 
values with age (juvenile to adult) has been 
documented in MVD; this does not 
coordinate with ill health.
• Generally, TSBA tests in MVD dogs not 
quantitatively related to histologic severity.
• Dogs with zone 3 degenerative lesions 
(described above) may develop progressive 
hepatopathy leading to HE, portal hyperten-
sion, APSS, ascites, and rarely portal venous 
TE; rare syndrome.
Small-breed dogs with high incidence of 
PSVA affected.
TSBA can be used to screen young dogs (≥16 
weeks of age) in breeds known to have high 
prevalence of PSVA/MVD.
Bitches with MVD and even minimally 
symptomatic PSVA carry litters to term.
SYNONYMS
• Congenital portal hypoperfusion.
• Hepatic microvascular dysplasia.
• Microscopic portovascular dysplasia.
• Portal venous hypoplasia.
Confused Terminology
• Intrahepatic portal venous atresia not 
synonymous with MVD.• Portal venous hypoplasia not interchange-
able as histologic diagnostic term for MVD.
SEE ALSO
• MVD = microvascular dysplasia.
• NCPH = noncirrhotic portal hypertension.
Allen L, Stobie D, Mauldin GN, Baer KE. 
Clinicopathological features of dogs with 
hepatic microvascular dysplasia with and 
without portosystemic shunts: 42 cases 
(1991–1996). J Am Vet Med Assoc 2000, 
214:218–220.
Schermerhorn, T, Center SA, Dykes NL, 
et al. Characterization of hepatoportal 
microvascular dysplasia in a kindred of cairn 
terriers. J Vet Intern Med 1996, 
10:219–230.
Toulza O, Center SA, Brooks MB, et al. 
Protein C deficiency in dogs with liver 
disease. J Am Vet Med Assoc 2006, 
229:1761–1771.
Sean P . McDonough. (continued)  Hepatoportal Microvascular Dysplasia

642  Blackwell’s Five-Minute Veterinary Consult  
HHepatosupportive Therapies
  BASICS
OVERVIEW
• Goals of treatment of hepatobiliary disease 
involve identifying and treating the underlying 
cause and attenuating pathophysiologic 
mechanisms common to many hepatobiliary 
diseases, including inflammation, oxidative 
damage, and fibrosis.
• Hepatosupportive agents, including 
prescription drugs and dietary supplements 
(vitamins, minerals, and nutraceuticals), have 
received much attention for their concomi-
tant role in treatment of hepatic disease.
• These medications purportedly enhance 
natural defense mechanisms to inhibit 
inflammation and fibrosis, prevent hepatocyte 
apoptosis, and protect against oxidant injury.
  DIAGNOSIS
N/A
  TREATMENT
See Medications.
S-adenosylmethionine (SAMe)
• Endogenous molecule produced from the 
amino acid methionine and ATP by the 
enzyme methionine adenosyltransferase 
synthetase.
• Mechanisms of action—anti-apoptotic, 
stabilization of cell membranes, modulates 
cytokine expression, antioxidant activity 
through enhancement of glutathione levels.
• Indications—necroinflammatory, choles-
tatic, metabolic, toxic, and ischemic 
hepatopathies.
• Dosage—20 mg/kg/day PO (dogs and cats).
• Dosage information and comments—best 
administered in fasted  state; enteric-coated 
tablets should not be broken or crushed; lack 
of bioavailability may be issue in over-the-
counter human products.
• Adverse effects and precautions—side 
effects are rare; post-pill nausea and lack of 
appetite have been reported in dogs (typically 
transient); some cats may develop post-pill 
vomiting.
• Notes—despite lack of supporting 
evidence, SAMe is frequently prescribed for a 
variety of hepatobiliary disorders, as it is generally considered safe and has the potential 
for benefit.
N-acetylcysteine (NAC)
• Stable formulation of the amino acid 
l-cysteine.
• Mechanisms of action—blocks polymor-
phonuclear leukocyte (PMN)–endothelial cell 
adhesion, PMN activation, and cytokine 
release (anti-inflammatory); improves tissue 
oxygen delivery; antioxidant activity.
• Indications—acute liver failure, toxic 
hepatopathies (acetaminophen), and severe 
feline hepatic lipidosis.
• Dosage—140 mg/kg IV once, then 70 mg/kg 
IV q6h or 100 mg/kg/day CRI (dogs and cats).
• Dosage information and comments—
administer through a nonpyrogenic filter 
using a 10% solution diluted 1 : 2 or more 
• Adverse effects and precautions —vomiting 
if given orally (use oral SAMe instead).
• Notes—use of NAC should be considered 
in any veterinary patient fitting criteria for 
acute  liver failure.
• Cytoprotective hydrophilic dihydroxylated 
bile acid.
• Mechanisms of action—replaces hepatotoxic 
bile acids, stabilization of mitochondrial 
function, immunomodulatory, anti-  apoptotic, 
stimulation of choleresis.
• Indications —cholestatic, necroinflamma-
tory, metabolic hepatopathies; asymptomatic 
or mildly symptomatic dogs with gallbladder 
mucocele.
• Dosage —15 mg/kg PO q24h (dogs and cats).
absorption enhanced with food ; can increase 
to q12h dosing with severe cholestasis.
• Adverse effects and precautions—rare 
vomiting and diarrhea; avoid in cases of 
complete bile duct obstruction; may increase 
bioavailability of vitamin E and cyclosporine.
Silymarin
• Group of flavonoids of which silybin is the 
major active component.
• Mechanisms of action—antioxidant 
(reactive oxygen species scavenger), 
 anti-inflammatory, modulates hepatocyte 
transport, increases hepatic protein synthesis, 
antifibrotic, choleretic.
• Indications —toxic ( Amanita  mushroom), 
cholestatic, and necroinflammatory 
• Dosage —silymarin: 20–50 mg/kg/day 
divided q6–8h PO (dogs and cats); Siliphos®: 
3–6 mg/kg/day PO.
• Dosage information and comments—  
bioavailability is variable.
• Adverse effects and precautions—no side 
effects; silymarin may inhibit the activity of 
drug-metabolizing enzymes.Vitamin E
• Nutritional antioxidant found in all cell 
• Mechanisms of action—antioxidant, 
anti-inflammatory.
• Indications —cholestatic and necroinflam-
matory hepatopathies.
• Dosage —10–15 IU/kg/day PO of 
alpha-tocopherol acetate (dogs and cats).
• Dosage information and comments—may 
need higher doses with severe cholestasis; 
parental formulation available and should be 
considered in animals with severe 
cholestasis.
• Adverse effects and precautions—none.
  FOLLOW-UP
N/A
• PMN = polymorphonuclear leukocyte.
• SAMe = S-adenosylmethionine,
Webster CR, Cooper J. Therapeutic use of 
cytoprotective agents in canine and feline 
hepatobiliary disease. Vet Clin North Am 
Small Animal Pract 2009, 39:631–652.

Canine and Feline, Seventh Edition  643
HHepatotoxins
  BASICS
• Endogenous or exogenous substances (drugs, 
xenobiotics, toxins) that cause hepatic injury. 
• Direct—(dose dependent): causes predictable 
injury. • Idiosyncratic—(dose independent): 
• Liver highly susceptible because of location 
and central role in metabolism and detoxifica-
tion; liver most commonly reported organ 
associated with true adverse drug reactions. 
• Mechanisms of damage are direct (active 
metabolic byproducts) or indirect (oxidative 
injury from free radical metabolites). • May 
cause hepatocellular or cytolytic injury 
(necrosis and apoptosis), cholestasis, 
immunologic (innocent bystander or 
hapten-mediated), or mixed histopathologic 
patterns of injury.
• Hepatobiliary. • Nervous—hepatic 
encephalopathy (HE). • Hemic/lymphatic/
immune—disseminated intravascular 
coagulation (DIC). • Renal—proximal 
tubular necrosis or renal tubular acidosis/
Fanconi syndrome; hepatorenal 
syndrome (rare).
GENETICS
See Breed Predilections.
Etiology dependent.
Species
• Siamese cats—some kindreds have high risk 
(reduced glucuronide formation). • Dog 
breeds at risk for selected drug toxicity—
Doberman, Samoyed: sulfonamide anti -
biotics; Doberman: amiodarone; Labrador 
retriever: nonsteroidal anti-inflammatory 
drugs (NSAIDs); cocker spaniel, German 
shepherd: phenobarbital; herding breeds: 
ABCB1  substrates (ATP-binding cassette 
subfamily B member 1 gene, encodes for 
P-glycoprotein).
Any age.
SIGNS
• May reflect chronic long-term or single 
acute exposure. • Detailed history essential—environmental, drug, and past medical 
history.
• Malaise to moribund state. • Hyporexia, 
vomiting, diarrhea, jaundice, neurologic signs.
• May be clinically normal if intoxication 
observed. • Variable body temperature 
(hypothermic to febrile), vomiting, 
diarrhea, weakness. • Icterus—overt or 
progressive (48–96 hours post exposure). 
• Ascites—rare (grave sign). • HE or coma. 
• Hemorrhage; petechia; ecchymosis (if 
DIC present).
CAUSES
Any drug, toxin, or xenobiotic may cause 
hepatotoxicity, variable severity, any 
individual.
Common Drugs
• Acetaminophen. • Amiodarone. 
• Azathioprine. • Azole antifungals. 
• Beta-lactam antibiotics. • Cyclosporine. 
• Diazepam (cat, oral only). • Glipizide (cat). 
• Glucocorticoids (dog). • Glucosamine-
based joint supplements (dog). • Griseofulvin 
(cat). • Imidocarb. • Lomustine (dog). 
• Methimazole (cat). • Mitotane (dog). 
• NSAIDs (dog). • Phenobarbital (dog). 
• Sulfonamide antibiotics (dog). 
• Tetracyclines. • Toceranib (cat). 
• Zonisamide (dog).
Common Environmental Toxins
• Amanita  mushrooms (amanitin-containing 
mushrooms). • Aflatoxins/mycotoxins. 
• Blue-green algae ( Cyanobacteria ). 
• Chlorinated compounds. • Cycad (sago 
palm nuts). • Heavy metals (Pb, Zn, Mn, Ar, 
Fe, Cu). • Phenolic chemicals (especially cats). 
• Gossypol from cottonseed.
Endotoxins
• Enteric organisms— Clostridium perfrin -
gens; Gram-negative organisms. • Food 
poisoning—  Staphylococcus ; Escherichia coli ; 
Salmonella .
Nutritional/Herbal
• Atractylis gummifera . • Black cohosh. 
• Callilepis laureola . • Chaparral. • Chinese 
herbal medicines (certain constituents, 
contents difficult to characterize). • Comfrey 
extracts (pyrrolizidine alkaloids). • Germander. 
• Greater celandine. • Green tea extract. 
• Kava kava (dogs). • Licorice. • Lipoic acid 
(cats). • Mistletoe. • Pennyroyal. • Senna. 
• Usnic acid. • Valerian. • Xylitol (sugar 
substitute; dogs).
• Medications influencing hepatic metabolism. 
• Antecedent hepatic disease. • Nutritional 
and antioxidant status. • Hepatic copper 
accumulation. • Prior exposure to hepatotoxic 
compounds.  DIAGNOSIS
• Infectious disorders affecting liver/biliary 
tract—leptospirosis, cholangitis/
cholecystitis, feline infectious peritonitis, 
toxoplasmosis, rickettsial diseases, 
histoplasmosis. • Acute necrotizing 
pancreatitis. • T raumatic or hypoxic liver 
injury. • Chronic hepatitis. • Hepatic 
neoplasia. • Diagnosis of hepatotoxicity 
requires integration of history, environment, 
food, medications, and temporal 
relationship(s).
• PCV and total solids—often normal or 
high in acute hepatotoxicosis (shock or 
dehydration). • Alanine aminotransferase 
(ALT)—reflects cellular membrane damage 
and leakage; may be 10- to 100-fold normal; 
prognosis not correlated with magnitude of 
increase. Increased ALT may precede increases 
in bilirubin and alkaline phosphatase (ALP). 
Some toxins suppress hepatic enzyme synthesis, 
impairing clinical recognition of hepatic injury 
(e.g., blue-green algae, aflatoxin). • ALP—
usually continues to rise for days/weeks while 
ALT falls. • Aspartate aminotransferase 
(AST)—may reflect more severe injury 
(mitochondrial) than ALT; use creatine kinase 
to differentiate hepatic damage from 
myonecrosis. • Bilirubin, albumin, blood 
urea nitrogen, cholesterol, glucose—variable.
• Coagulation profile—monitor for DIC. 
• Pre- and post-prandial total serum bile 
acids—assess hepatic function in nonicteric 
patients. • Low protein C activity—  
biomarker for blocked protein transcription 
in aflatoxicosis.
IMAGING
• Abdominal radiography—acute toxicity: 
normal to large liver; chronic injury: variable 
liver size. • Abdominal US—variable 
echogenicity, hepatic size, margins; assess for 
presence of ascites.
• Hepatic biopsy—seldom indicated in acute 
toxicity; helpful in chronic hepatic injury 
without obvious cause; laparoscopy yields 
better samples than needle biopsies. • Fine-
needle aspiration—helpful if neoplasia or 
infectious agents visualized; no pathogno-
monic findings for toxicity.
Variable; depends on toxin, mechanism of 
cell injury, acinar zone of metabolism or 
product accumulation, vascular injury, and 

644  Blackwell’s Five-Minute Veterinary Consult  
Inpatient—critical care setting.
• Decontamination—if intoxication observed 
and animal presented promptly, decontamina -
tion with emetics, adsorbents, and cathartics 
can be beneficial. • Prevention/correction of 
shock imperative. • Crystalloid therapy—
maintain hepatic perfusion to improve 
oxygenation and toxin removal; administer 
maintenance requirements; avoid lactate-con -
taining fluids in fulminant hepatic failure; 
provide adequate potassium supplementation 
and monitor, hypokalemia potentiates clinical 
signs of HE. • Colloid administration—plasma 
initially preferred for delivery of clotting and 
anticoagulant factors followed by cautious use 
of synthetic colloid, if oncotic pressure low. 
• Coagulopathy—vitamin K1 (0.5–1.5 mg/kg 
SC/IM q12–24h); fresh whole blood or fresh 
frozen plasma as needed ( caution : stored blood 
products may have high ammonia concentra -
tion, causing HE). • Nasal oxygen—if 
compromised peripheral perfusion (hypoten -
sion) or pulmonary edema; may improve 
oxygen delivery to hepatic tissue. • Monitor 
urine output—diuretics as appropriate (see 
Acute Kidney Injury). • Hypoglycemia—
administer dextrose as needed.
ACTIVITY
DIET
• Protein—normal, unless overt HE. 
• Nutritional support—if normal body 
condition score and acute disease, can wait up 
to 48h for patient to voluntarily ingest food; 
then consider nasoesophageal/esophageal tube 
feeding. Parenteral only if unable to feed 
enterally; can cause severe complications. 
• Energy—begin with ~20–30% resting 
energy requirement (RER), then gradually 
increase to full RER over 3–5 days.
• Potential for 3–10 days of ICU. • Many 
recover but postnecrotic cirrhosis, acquired shunt -
ing, and chronic hepatitis can develop later.
Surgical/laparoscopic liver biopsies—generally 
not indicated.
• Discontinue  offending drug, if present. 
• See Hepatic Failure, Acute. • Antioxidant 
therapy— N-acetylcysteine (140 mg/kg IV load, followed by 70 mg/kg IV q6–8h, give 
over 20 min); S-adenosylmethionine 
(20 mg/kg enteric-coated tablet PO q24h, 
on empty stomach). • Silybin—active 
component of silymarin/milk thistle extract 
(2–5 mg/kg q24h PO); may augment liver 
regeneration; antioxidant, hepatoprotective, 
antifibrotic effects. • Ursodeoxycholic 
acid—primarily for chronic hepatopathies 
(15 mg/kg/day PO with food). • B-complex 
vitamins—parenteral; cofactors for hepatic 
metabolism. • Antiemetics—if indicated. 
• Antacids—if portal hypertension/gastric 
ulceration suspected. • Antibiotics—  
ampicillin/metronidazole, if HE or bacterial 
translocation suspected. • Lactulose—orally 
(0.5 mL/kg q8h) or retention enema 
(diluted 1 : 2 following cleansing enema) 
if HE suspected.
Avoid known hepatotoxic drugs.
Caution when catheterizing large vessels or 
diagnostic needle aspirates/biopsies if 
coagulopathic.
Avoid drugs that require or inhibit hepatic 
Alternative antioxidants—vitamin E 
(d-α-tocopherol acetate 10 IU/kg q24h PO); 
vitamin C (ascorbic acid 500–1000 mg/dog 
q24h PO, 125 mg/cat q12h PO).
  FOLLOW-UP
• Prevent hypothermia. • Blood glucose, 
electrolytes, packed cell volume—frequently; 
fluctuations occur rapidly in critically ill patients. 
• CBC, serum biochemical analyses, coagulation 
tests—monitor q48h or as warranted.
Close scrutiny of environment and future 
• DIC, hemorrhage. • HE. • Progressive 
hepatic failure. • Postnecrotic cirrhosis with 
acquired shunting/ascites.
EXPECTED COURSE AND  
PROGNOSIS
• 2–5 days to estimate prognosis. • Negative 
indicators—intractable emesis, hematemesis, 
intolerance to supportive treatments, oliguria, 
DIC, HE, decline of ALT with increasing 
bilirubin and/or decreasing serum albumin/
cholesterol. • Positive indicator—ALT 
declining by 20–30% or more every 48–72 
hours, with other evidence of improvement. • Postnecrotic cirrhosis—possible in 2–6 
months.
• Hepatitis. • Fibrosis. • HE. • Hepatic 
lipidosis (cats). • Icterus. • Ascites. 
• Hypoglycemia. • Sepsis.
• Young animals may have greater exposure 
risk for toxin ingestion; <16 weeks of age: 
immature hepatic metabolic and excretory 
pathways. • Older animals may have 
diseases requiring drug therapies, increasing 
their risk.
None
SEE ALSO
• Cirrhosis and Fibrosis of the Liver. 
• Hepatic Encephalopathy. 
• Hepatic Failure, Acute. 
• ALP = alkaline phosphatase. 
• ALT = alanine aminotransferase. 
• HE = hepatic encephalopathy. 
drug. 
• RER = resting energy requirement.
poison-control •https://www.
petpoisonhelpline.com
Peterson ME, Talcott PA. Small 
Animal Toxicology. St. Louis, MO: 
Saunders, 2006.
T repanier LA. Drug-associated liver disease. 
In: Bonagura JD, T wedt DC, eds., Kirk’s 
MO: Saunders, 2014, pp. 575–579.
Author  Jennifer M. Reinhart
editors acknowledge the prior contribu -
tions of Michael D. Willard and Sharon A. 
Center.
available onlineHepatotoxins   (continued)

Canine and Feline, Seventh Edition  645
HHepatozoonosis
  BASICS
OVERVIEW
• Disease caused by infection with the 
protozoan Hepatozoon americanum  or 
Hepatozoon canis ; here the focus is on 
systemic infection with Hepatozoon 
americanum —the primary cause of American 
canine hepatozoonosis.
• Hepatozoon canis  is less prevalent in the 
United States than Hepatozoon americanum ; it 
is also less virulent and infections are typically 
subclinical.
• Infection typically involves muscle and bone.
• Dogs—more common in the southern and 
southeastern United States.
• Cats—uncommon in the United States.
• No age, breed, or sex predilections.
SIGNS
• Lameness and stiff gait.
• Waxing and waning fever.
• Mucopurulent ocular discharge.
• Hyperesthesia.
• Weight loss and cachexia.
• Polyuria and polydipsia in some cases if 
glomerulonephritis is present.
• Amblyomma maculatum —tick ingestion.
• Ingestion of infected paratenic hosts 
(predation or scavenging).
  DIAGNOSIS
• Endocarditis.
• Immune-mediated polyarthritis or 
polymyositis.
• Chagas disease.
• Meningitis/meningoencephalitis.
• Hypertrophic osteopathy.
• Ehrlichiosis.
• Neutrophilic leukocytosis, usually profound 
(20,000–200,000 white blood cells 
[WBC]/ μL), sometimes with a left shift.
• Anemia—mild to moderate, usually 
nonregenerative.
• Usually have a normal platelet count unless 
there is a coinfection.
• High serum alkaline phosphatase (ALP) 
activity.
• Decreased serum urea nitrogen concentration.• Despite severe myositis, creatinine kinase 
concentrations are often within reference 
range.
Blood smear—in rare cases identify organisms 
in circulating neutrophils and monocytes.
IMAGING
Radiographs—pelvis, lumbar vertebrae, and 
long bones; periosteal proliferation.
• Muscle biopsy.
• PCR on blood or muscle.
• Muscle atrophy—“onion-skin” meronts and 
pyogranulomatous myositis.
• Enlarged liver and spleen—may contain 
meront stages on histopathology.
• Periosteal proliferation of bone.
  TREATMENT
• Inpatient—for severe pain; provide 
symptomatic relief.
• Pain management—as for any musculoskeletal 
disease.
• General activity level and appetite—depend 
on pain level.
• Most dogs will require lifelong treatment to 
maintain clinical remission.
• Mostly palliative, as no treatments have 
been shown to clear infection.
• Combination therapy (TCP) initially:
◦ T rimethoprim/sulfadiazine—15 mg/kg 
PO q12h for 14 days.
◦ Clindamycin—10 mg/kg PO q8h for 14 days.
◦ Pyrimethamine—0.25 mg/kg PO q24h 
for 14 days.
• Followed with long-term therapy—
decoquinate 10–20 mg/kg PO q12h for up to 
33 months (possibly indefinite).
• Ponazuril 10 mg/mg PO q12h for 28 days 
has shown promise as an alternative initial 
treatment; long-term therapy with 
decoquinate is still necessary.
• Glucocorticoids—may give temporary 
relief, but are not routinely recommended.
(NSAIDs) may provide analgesia.
None  FOLLOW-UP
• Difficult to monitor organisms in 
chronically infected dogs.
• Best to monitor for clinical improvement.
• Control ticks within the household or 
kennel.
• Avoid predation and scavenging.
• Glucocorticoids—may exacerbate clinical 
disease.
• Radiographic changes may never occur.
• T reatment typically results in improvement 
of clinical signs and quality of life, but does 
not cure the infection.
• T reatment is likely to be needed for the 
remainder of the patient’s life.
• If clinical relapse occurs, repeat of both 
initial and long-term treatments is 
No reported risk to humans.
drug.
• TCP = trimethoprim-sulfa, clindamycin, 
pyrimethamine.
• WBC = white blood count.
Allen KE, Johnson EM, Little SE. 
Hepatozoon spp infections in the United 
States. Vet Clin North Am Small Anim 
Pract 2011, 41(6):1221–1238.
Baneth G. Perspectives on canine and feline 
hepatozoonosis. Vet Parasitol 2011, 
181(1):3–11.

646  Blackwell’s Five-Minute Veterinary Consult  
HHiatal Hernia
  BASICS
OVERVIEW
• Herniation of abdominal contents (most 
commonly the stomach) cranial to the 
diaphragm into the thorax through the 
esophageal hiatus. Four types have been 
described:
◦ Type I (sliding; most common).
◦ Type II (paraesophageal).
◦ Type III (includes elements of both types 
I and II).
◦ Type IV (herniation of organs other than 
the stomach).
• May be congenital or acquired—acquired 
most commonly associated with upper 
respiratory disease (brachycephalic syndrome, 
laryngeal paralysis).
• Dogs > cats.
• Congenital reported in English and French 
bulldogs, shar‐peis and chow chows; acquired 
common in brachycephalic breeds.
SIGNS
• Most signs secondary to gastroesophageal 
reflux (GER) and esophagitis.
• Lip smacking.
• Inability to gain weight.
• Respiratory distress.
Congenital. Acquired— traumatic event ± 
severe upper respiratory disease; brachycephalic 
  DIAGNOSIS
Other causes of weight loss or regurgitation 
such as megaesophagus, esophagitis, vascular 
ring anomaly, etc.
No specific abnormalities. May find 
inflammatory leukogram secondary to 
associated pneumonia.
N/A
IMAGING
Cranial displacement of stomach. Soft tissue 
mass in caudal thorax adjacent to diaphragm. Gas‐filled viscera in thorax. Infrequently 
diagnosed on survey thoracic radiographs 
alone.
Positive Contrast Esophagram
Preferably performed using videofluoroscopy. 
Helps to confirm diagnosis and differentiate 
between types I and II hernias. Can also 
diagnose associated GER and esophageal 
dysmotility. False‐negative studies common 
due to highly intermittent and dynamic 
nature of hiatal herniation.
Upper gastrointestinal endoscopy can 
occasionally document herniation. However, 
effects of herniation such as esophagitis or 
stricture may be detectable if herniation does 
not occur during study.
  TREATMENT
Not all dogs that have radiographic evidence 
require treatment. Conservative therapy can 
be successful in controlling clinical signs in 
dogs with mild hiatal herniation.
Medical Management
• Can often be managed as outpatient unless 
animal has severe aspiration pneumonia.
• Reduce gastric acid secretion (proton pump 
inhibitors are superior to H2 receptor 
antagonists).
• Increase rate of gastric emptying and 
increase lower esophageal sphincter (LES) 
tone (prokinetic agents such as cisapride).
• Provide esophageal mucosal protection 
(sucralfate).
• Feed a low‐fat diet in an elevated position.
• 30‐day trial of medical management before 
surgery often recommended; not all patients 
require surgery.
• Patients nonresponsive to medical therapy.
• T reat with antacids and prokinetics prior to 
surgery.
• Surgical procedures (used alone or in 
combination)—phrenoplasty; esophagopexy; 
left‐sided gastropexy.
• H2 receptor antagonists—increase gastric 
pH and reduce esophagitis secondary to GER:
◦ Famotidine 0.5–1 mg/kg PO/IV q12h.
◦ Ranitidine 1–2 mg/kg PO/IV q8–12h.
• Proton pump inhibitors—more potent than 
H2 receptor antagonists:
◦ Omeprazole 0.7–1.5 mg/kg PO q12h.
◦ Pantoprazole 0.7–1.5 mg/kg IV q12h.• Prokinetics—increase gastric emptying:
◦ Metoclopramide 0.2–0.5 mg/kg PO 
q6–8h or 1–2 mg/kg/24h IV as CRI.
◦ Cisapride 0.2–0.5 mg/kg PO q8–12h.
  FOLLOW‐UP
• Long‐term medical therapy may be 
indicated in both surgically and conservatively 
managed patients.
• Postoperative—monitor for dyspnea, 
worsening regurgitation (may require second 
surgery), abdominal distension that could 
result from overtightening of hiatus resulting 
in inability to eructate.
Continuation of clinical signs, bloat episodes.
• Overall prognosis is good.
• When medical management fails, surgical 
intervention leads to positive outcome in 
majority of cases.
Often found in dogs with brachycephalic 
airway syndrome or other upper airway 
obstructive diseases. Hypothesized that 
decreases in intrathoracic pressures generated 
may pull the stomach into the thorax through 
the hiatus. Gastroesophageal reflux can 
worsen clinical signs of upper respiratory 
disease due to irritation of upper respiratory 
area or associated bronchospasm of the lower 
airway.
• GER = Gastroesophageal reflux.
• LES = Lower esophageal sphincter.
Callan MB, Washabau RJ, Saunders HM, 
et al. Medical treatment versus surgery for 
hiatal hernias. J Am Vet Med Assoc 1998, 
213:800.
Lorinson D, Bright RM. Long‐term outcome 
of medical and surgical treatment of hiatal 
hernias in dogs and cats: 27 cases (1978–
1996). J Am Vet Med Assoc 1998, 
213:381–384.
Sivacolundhu RK, Read RA, Marchevsky 
AM. Hiatal hernia controversies: a review of 
pathophysiology and treatment options. 
Aust Vet J 2002, 80:48–53.
Authors  Kathryn A. Pitt and Philipp D. 
Mayhew

Canine and Feline, Seventh Edition  647
HHip Dysplasia
  BASICS
A developmental syndrome characterized in 
growing animals by excessive laxity of the 
coxofemoral joint that results in secondary 
osteoarthritis (OA) of the coxofemoral joints 
in the adult animal.
• Developmental defect initiated by genetic 
predisposition to subluxation of immature 
hip joint.
• Poor congruence between femoral head and 
acetabulum; creates abnormal forces across 
joint; interferes with normal development 
(leading to irregularly shaped acetabula and 
femoral heads); overloads articular cartilage 
(causing microfractures and OA).
GENETICS
• Complicated, polygenetic transmission. 
Genetic markers for diagnosis and prevention 
are under development but are not standard-
ized or routinely used.
• Expression is determined by interaction of 
genetic and environmental factors, the latter 
including overall excess caloric consumption 
and excess calcium during growth.
• Heritability index—depends on breed, but 
generally estimated at 0.3.
• One of most common skeletal diseases 
encountered clinically in dogs.
• Actual incidence unknown; depends on breed.
• Incidence in cats significantly lower than 
dogs.
Species
Dog, rarely cat.
• Large-breed dogs—Saint Bernard, German 
shepherd, Labrador retriever, golden retriever, 
Rottweiler.
• Smaller-breed dogs—may be affected; in 
fact, incidence of disease in pugs is highest of 
all breeds, approaching 70%; small-breed 
dogs less likely to exhibit clinical signs.
• Cats—more commonly affects purebred cats; 
reportedly affects ~18% of Maine coon cats.
• Onset of clinical signs varies with 
severity of hip laxity in immature dog 
and with worsening secondary OA in 
mature dog.
• Clinical signs—may develop after 4 months 
of age in dogs with severe laxity; may also 
develop at any age after onset of secondary OA.
• Clinical signs are biphasic in dogs; young 
dogs often exhibit most severe clinical signs between 6 and 12 months of age; clinical 
signs often diminish in animals 12–18 
months of age, worsening again in older dogs 
in 4–8-year age period.
• Dogs—none.
• Cats—more common in female cats.
SIGNS
• Severity of signs depends on degree of joint 
laxity, degree of OA, and chronicity of disease.
• Early—related to joint laxity.
• Later—related to severity of OA.
• Decreased activity.
• Difficulty or slow rising.
• Reluctance to run, jump, or climb stairs.
• Intermittent or persistent hind limb 
lameness—often worse after exercise.
• Pelvic limb lameness may be unilateral or 
• Bunny-hopping or swaying gait.
• Narrow stance in hind limbs.
• Pain on palpation or manipulation of hip 
joint(s); particularly extension.
• Increased joint laxity (positive Ortolani 
sign)—characteristic of early disease; may not 
be finding in chronic cases owing to 
periarticular fibrosis.
• Crepitus during hip motion.
• Decreased range of motion in hip joints.
• Atrophy of thigh muscles.
CAUSES
• Genetic predisposition for hip laxity.
• Rapid weight gain may be associated with 
onset of clinical signs due to increased 
demands on joint.
• Nutritional influences, particularly excess 
caloric intake in young dog and calcium 
>1.6% in diet on dry-matter basis, increase 
phenotypic expression, development of hip 
dysplasia (HD), and progression of disease.
• Decreased gluteal and caudal thigh muscle 
mass—increase expression and progression.
• Overweight puppies fed in excess of caloric 
requirements for normal growth at risk for 
increased incidence of HD.
• Additional calcium supplementation in diet 
of young large-breed dogs contraindicated 
and may predispose to development of HD.
  DIAGNOSIS
• Cranial cruciate ligament rupture—up to 
⅓ of dogs referred for treatment of HD 
actually suffer from concurrent cranial 
cruciate rupture; cranial cruciate ligament 
rupture must remain alternative diagnosis for lameness in large-breed dogs until 
definitively eliminated from consideration.
• Degenerative myelopathy.
• Lumbosacral instability.
• Unilateral or bilateral stifle disease.
• Polyarthropathies.
IMAGING
• Ventrodorsal hip-extended radiographs—
commonly used for diagnosis; may need 
sedation or general anesthesia for accurate 
positioning.
• Early radiographic signs—subluxation of 
hip joint with poor congruence between 
femoral head and acetabulum; initially 
normally shaped acetabulum and femoral 
head; with disease progression, shallow 
acetabulum and flattened femoral head.
• Radiographic evidence of OA—flattening of 
femoral head; shallow acetabulum; periarticular 
osteophyte production; thickening of femoral 
neck; sclerosis of subchondral bone; 
periarticular soft tissue fibrosis. Remodeling of 
femoral neck is uncommon in cats.
• Distraction radiographs—quantify joint 
laxity; may accentuate laxity for more 
accurate diagnosis. Distraction radiographic 
procedures such as PennHip® have been 
standardized and allow better prediction of 
dogs likely to develop secondary hip OA and 
better selection of dogs for breeding potential.
• Dorsal acetabular rim view radiographs—
evaluate acetabular rim; assess dorsal coverage 
of femoral head. Clinical efficacy of such 
views in diagnosis and treatment of HD has 
not been definitively established.
• Commercial genetic markers are under 
development but not in widespread use at this 
time.
• Arthroscopy of hip joint has been described 
in diagnosis of HD, but does not add useful 
clinical information regarding treatment.
• Early—normal conformation of femoral 
head and acetabulum; may note joint laxity 
and excess synovial fluid.
• With progression—malformed acetabulum 
and femoral head; synovitis; articular cartilage 
degeneration. Formation of periarticular 
osteophytes leads to radiographic formation 
of “Morgan’s line,” linear formation of 
enthesiophytes at origin of joint capsule on 
femoral neck.
• Chronic—may note full-thickness cartilage 
erosion.
  TREATMENT
• May treat with conservative medical 
therapy or surgery.

648  Blackwell’s Five-Minute Veterinary Consult  
H• Depends on patient’s size, age, and 
intended function; severity of joint laxity; 
degree of OA; clinician’s preference; financial 
considerations of owner.
• Physical therapy (passive joint motion)—
decreases joint stiffness; helps maintain 
muscle integrity.
• Swimming (hydrotherapy)—excellent 
nonconcussive form of physical therapy; 
encourages joint and muscle activity without 
exacerbating joint injury.
ACTIVITY
• As tolerated.
• Swimming—recommended to maintain 
joint mobility while minimizing weight-
bearing activities.
DIET
• Weight control—important and first goal 
of therapy; decrease load applied to painful 
joint; minimize weight gain associated with 
reduced exercise.
• Supplementation with omega-3 fatty acids 
(in commercial diets or as food additive) 
beneficial to decrease pain and inflammation 
and improve function. While optimum 
dosage/feeding of omega-3 fatty acids yet to 
be determined, clinical efficacy of commercial 
diets containing 1.7–3.4% of omega-3 fatty 
acids and precursors has been established.
• Discuss heritability of the disease, recom-
mend neutering of affected animals and 
elimination as breeding sources.
• Explain that medical therapy is palliative.
• Warn client that joint degeneration often 
progresses unless corrective osteotomy 
procedure is performed early in disease.
• Explain that surgical procedures can 
salvage joint function once severe joint 
degeneration occurs.
Triple, Double, or 2.5 Pelvic Osteotomy
• Corrective procedure; designed to 
reestablish congruity between femoral head 
and acetabulum.
• Immature patient (6–10 months of age) 
without signs of OA.
• Rotate acetabulum—improve dorsal 
coverage of femoral head; correct forces acting 
on joint; minimizes progression of OA, but 
OA frequently progresses on radiographs even 
though progression not clinically apparent.
• Surgical procedure necessitates implanta-
tion of surgical implants, commonly bone 
plate and screws specially designed for 
procedure; large dogs may necessitate use of 
two bone plates; outcomes improved and 
complication rates decreased with use of 
locking implants.
Juvenile Pubic Symphysiodesis
• Pubic symphysis is fused at early age (8–16 
weeks) using electrocautery.• Requires extremely early diagnosis of 
condition, or use as preventative in nonbreed-
ing animals to decrease need for more 
aggressive surgical procedure in dogs likely to 
develop secondary OA or more several clinical 
signs.
• Causes ventroversion of acetabulum during 
growth to better cover femoral head.
• Improves joint congruence and stability—
similar effects to triple pelvic osteotomy 
without osteotomy and surgical implants.
• Minimal morbidity; easy to perform—must 
be performed very early (ideally 3–4 months 
of age) to achieve effect; minimal effect 
achieved if performed after 5 months of age.
Total Hip Replacement
• Indicated to salvage function in mature 
dogs with severe degenerative disease 
unresponsive to medical therapy.
• Multiple systems exist to replace both 
acetabular and femoral head surfaces and 
comprising both cemented and noncemented 
(ingrowth) implants; noncemented implants 
have best prognosis for long-term use and 
implant stability.
• Pain-free joint function—reported in >90% 
of cases.
• Unilateral joint replacement—provides 
acceptable function in ~80% of cases.
• Staged bilateral joint replacement now 
chosen by 50% of owners.
• Complications—luxation; femoral fracture, 
sciatic neuropraxia; infection; incidence of 
infection decreased with use of noncemented 
implant systems compared to cemented systems.
Excision Arthroplasty
• Removal of femoral head and neck to 
eliminate joint pain.
• Extremely important to achieve smooth 
osteotomy close to femoral shaft.
• Primarily a salvage procedure—for 
significant OA; when pain cannot be 
controlled medically; when total hip 
replacement is cost-prohibitive.
• Best results—small, light dogs ( <20 kg); 
patients with good hip musculature.
• Can provide good results in larger dogs.
• Slightly abnormal gait often persists and 
consistently seen on objective gait analysis of 
patients, despite lack of lameness detection by 
owners or veterinarians on casual observation.
• Postoperative muscle atrophy—common, 
particularly in large dogs.
Denervation Procedure
• Surgical procedure described in anecdotal 
and research literature to reduce pain 
associated with HD.
• Does not improve joint conformation or OA.
• Little objective scientific evidence exists for 
this procedure’s effectiveness despite numerous 
clinical reports.
• Recent blinded studies suggest the treatment 
does not improve the treated hip, but may slow 
development of further clinical signs.  MEDICATIONS
• Analgesics and anti-inflammatory drugs—
minimize joint pain (and thus stiffness and 
muscle atrophy caused by limited usage); 
decrease synovitis.
• Medical therapy—does not correct 
biomechanical abnormality; degenerative 
process likely to progress; often provides only 
temporary relief of signs.
• Agents—carprofen (2.2 mg/kg POq12h or 
4.4 mg/kg PO q24h); etodolac (10–15 mg/kg 
PO q24h); deracoxib (3–4 mg/kg PO q12h 
for 1 week, then 2 mg/kg PO q12h); 
firocoxib (4 mg/kg PO q24h).
• Diet supplementation with omega-3 fatty 
acids (fish oils) decreases joint inflammation 
and provides pain relief; commercial diets 
containing 1.7–3.4% omega-3 fatty acids and 
precursors are most consistent and easiest 
method of administration.
• Nonsteroidal anti-inflammatory drugs—
gastrointestinal upset may preclude use in 
• Carprofen—reported to cause acute 
hepatotoxicity in some dogs.
• Polysulfated glycosaminoglycan injections, 
or oral glucosamine, and chondroitin sulfate—  
may have chondroprotective effect in OA, but 
recent evidence suggests are not or are only 
minimally efficacious.
• There are single reports of agents such as 
elk antler velvet suggesting their efficacy for 
OA, but no confirmation or widespread 
acceptance for efficacy.
• Prophylactic laser therapy, extracorporeal 
pulse therapy, and acupuncture have been 
suggested for treatment, but no documented 
evidence demonstrating efficacy of these 
modalities for OA despite numerous research 
studies.
• Stem cell therapy, primarily mesenchymal 
stromal cell extractions, have been investigated 
in research studies and individual clinical 
patients, but show no clinical benefit at present.
  FOLLOW-UP
• Clinical and radiographic monitoring—
assess progression.
• Medical treatment—clinical deterioration 
suggests alternative dosage or medication or Hip Dysplasia   (continued)

Canine and Feline, Seventh Edition  649
Hsurgical intervention; weight management is 
important continuing consideration in 
management of HD.
• T riple pelvic osteotomy—monitored radio  - 
graphically; assess healing, implant stability, 
joint congruence, and progression of OA; over 
50% of dogs may develop radiographic signs of 
OA after pelvic osteotomy, but clinical signs or 
their lack remain stable in spite of OA.
• Hip replacement—monitored radio -
graphically on annual basis; assess implant 
stability.
• Best prevented by not breeding affected dogs.
• Pelvic radiographs—may help identify 
phenotypically abnormal dogs; may not 
identify all dogs carrying the disease.
result in affected offspring.
• Special diets designed for rapidly 
growing large-breed dogs—may decrease 
severity.EXPECTED COURSE AND PROGNOSIS
Joint degeneration usually progresses—most 
patients lead normal lives with proper 
medical or surgical management.
Do not breed affected dogs; added weight 
owing to pregnancy may exacerbate clinical 
signs.
• HD = hip dysplasia.
Lister SA, Roush JK, Renberg WC, Stephens 
CL. Ground reaction force analysis of 
unilateral coxofemoral denervation for the 
treatment of canine hip dysplasia. Vet Comp 
Orthop T raumatol 2009, 22(2):137–141.Smith GK, Leighton EA, Karbe GT, 
McDonald-Lynch MB. Pathogenesis, 
diagnosis, and control of canine hip 
dysplasia. In: Johnston SA, Tobias KM, eds. 
Veterinary Surgery: Small Animal, 2nd ed. 
St. Louis, MO: Elsevier, 2018, pp. 964–992.
Upchurch DA, Renberg WC, Roush JK, et al. 
Administration of adipose-derived stromal 
vascular fraction and platelet rich plasma in 
dogs with coxofemoral osteoarthritis. Am J 
Vet Res 2016, 77:940–951.
Vezzoni A, Peck JN. Surgical management of 
hip dysplasia. In: Johnston SA, Tobias KM, 
eds. Veterinary Surgery: Small Animal, 2nd 
ed. St. Louis, MO: Elsevier, 2018, pp. 
992–1018.
Author  James K. Roush
available online (continued)  Hip Dysplasia

H650  Blackwell’s Five-Minute Veterinary Consult  
HHistiocytic Diseases—Dogs and Cats
  BASICS
Histiocytic diseases encompass a wide 
spectrum of heterogenous dendritic or 
macrophage-derived proliferative disorders. 
Most of these histiocytic diseases are of 
dendritic cell lineage and in dogs include 
cutaneous histiocytoma, Langerhans cell 
histiocytosis (LCH), reactive histiocytoses 
(cutaneous histiocytosis [CH] and systemic 
histiocytosis [SH]), and histiocytic sarcoma 
(HS) complex, with hemophagocytic HS 
representing the only macrophage-derived 
disease entity. In cats, histiocytic diseases are 
limited to feline progressive histiocytosis 
(FPH), HS, and feline pulmonary Langerhans 
cell histiocytosis (FPLCH). All of these 
disorders represent neoplastic processes, 
except for the canine reactive histiocytoses, 
which are inflammatory diseases associated 
with underlying immune dysregulation.
Canine
Cutaneous Histiocytoma
• Most common in young dogs; 50% of 
affected patients <2–3 years of age.
• Occurs in all breeds; predisposition in purebred 
dogs, particularly boxers and dachshunds, cocker 
spaniels, Great Danes, and bobtails.
Cutaneous LCH
• Rare entity in dogs, with similar signalment 
as for cutaneous histiocytoma.
• Occurs in many breeds.
CH
• Only described in the dog; age range: 2–13 
years.
• Most common in collies, border collies, 
Shetland sheepdogs, briards, Bernese mountain 
dogs (BMDs), and golden retrievers, with no 
clear age or sex predilection.
SH
• Disease predominantly affecting young to 
middle-aged dogs (2–8 years).
• Familial association in BMDs (male 
predilection), but other large-breed dogs are 
affected (e.g., Rottweiler, Labrador retriever, 
basset hound, Irish wolfhound).
HS
• Middle-aged or older dogs, uncommon 
in cats.
• Strong breed predilections in BMD and 
flat-coated retrievers (FCRs), with other 
predisposed breeds including Rottweiler, 
golden retriever, Labrador retriever, and 
miniature schnauzer.
Hemophagocytic Histiocytic Sarcoma (HHS)
• Dogs, very rarely cats.
• Similar signalment to HS.Feline
FPH
• Most common histiocytic disease in 
middle-aged to older cats (7–17 years).
FPLCH
Aged cats (10–15 years).
SIGNS
Canine
• Benign, solitary “button-like,” raised, 
well-circumscribed, hairless dermal neoplasm 
that typically spontaneously regresses within 
2–3 months.
• Common sites—head and limbs.
• Extremely low recurrence rates; de novo 
development or local metastasis rare.
• Multiple cutaneous histiocytomas with 
possible metastasis to lymph nodes and 
internal organs is a distinguishing feature 
from cutaneous histiocytoma.
• Delayed lesion regression common.
CH
• Multiple cutaneous/subcutaneous nodules 
that may wax and wane and spontaneously 
disappear, with new lesions appearing at 
different sites.
• Limited to the skin, subcutis, and local 
draining lymph node(s); lack of systemic 
extension beyond peripheral lymph nodes is a 
distinguishing factor from SH.
SH
• Cutaneous/subcutaneous lesions are similar to 
CH, with spontaneous remissions and relapses.
• Involvement of lymph nodes, bone marrow, 
spleen, liver, lung, kidneys, testes, and 
• Clinical signs include depression, anorexia, 
weight loss, conjunctivitis and respiratory 
difficulty.
HS
• Primary tumor sites include skin and 
subcutis, lung, lymph node, liver, spleen, and 
other sites; secondary sites of involvement 
commonly include liver, lung, and lymph node.
• Periarticular mass with synovial tissue 
involvement also reported.
• Clinical signs vary depending on organ 
HHS
• Similar but more severe clinical signs to HS 
(e.g., marked anemia and thrombocytopenia).
• Subtype tends to present in a more 
infiltrative manner, causing hepatospleno-
megaly and myelophthisis.
Feline
FPH
• Begins as nonpainful, nonpruritic, low-grade 
HS with indolent behavior initially.• Some cats develop invasive masses in lymph 
nodes and internal organs in the terminal stage.
FPLCH
Acute or chronic presentation of respiratory 
failure due to extensive obliteration of all lung 
lobes by ill-defined coalescing nodular masses 
extending from peribronchiolar locations 
with enlargement of tracheobronchial lymph 
nodes and other draining lymph nodes.
• Cutaneous histiocytoma is believed to 
represent a benign neoplasm with unique 
biologic behavior.
• SH/CH are believed to have an element of 
immune dysregulation.
• SH has probable familial causation in BMD.
• HS and HHS likely have a genetic origin 
due to breed predilections (specifically in 
BMD); abnormalities in tumor suppressor 
gene loci are potentially correlated to the 
development of HS in BMD and FCR.
• FPH—chronic antigenic stimulation is a 
possible triggering factor.
  DIAGNOSIS
• Differentiate from focal granulomatous 
diseases, other sarcomas, other round cell 
tumors, and each distinctive subtype of the 
histiocytic disease.
• Differentiate HHS from immune-mediated 
anemia/thrombocytopenia, myelodysplastic 
syndromes, leukemias, and tick-borne diseases.
HHS—moderate to severe anemia (often 
regenerative), thrombocytopenia, neutrophilic/
monocytic leukocytosis, increased liver enzymes, 
hypoalbuminemia, hypocholesterolemia.
• Immunohistochemistry—used to differenti-
ate cutaneous reactive histiocytosis from 
inflamed nonepitheliotropic T-cell lymphoma 
and HS from other sarcomas and round cell 
tumors.
• Serum ferritin—hyperferritinemia has been 
documented in dogs with HS and has 
potential as a biomarker for early screening.
IMAGING
• Thoracic radiography—pulmonary parenchy -
mal involvement commonly observed:
 ◦LCH—peribronchial.
 ◦SH—perihilar/sternal lymphadenopathy, 
pulmonary infiltrates.
 ◦HS/HHS—diffuse interstitial infiltrate, 
patchy consolidated areas, focal or 
multifocal nodules or mass lesions.
 ◦Feline LCH—diffuse bronchointerstitial 
pattern of miliary to nodular opacities 
throughout all lung lobes.

Canine and Feline, Seventh Edition  651
HH• Extremity radiography—soft tissue mass  
± lytic lesions may be noted for periarticular 
HS.
• Abdominal ultrasonography—hepatosplenic 
masses and lymphadenopathy characteristic of 
HS; diffuse hepatosplenomegaly with 
mottling and mild lymphadenopathy more 
common with HHS.
Cytology and histopathology of lesions—pro-
vides definitive diagnosis based upon specific 
cellular morphologic criteria.
  TREATMENT
Canine
• Surgical excision or cryosurgery is generally 
curative.
• Cutaneous histiocytomas usually spontane-
ously regress within 2–3 months.
• If localized, surgical removal may be curative.
• If multifocal or lymph node involvement, 
consider treatment with immunosuppressive 
drugs.
CH/SH
Cutaneous lesions may wax and wane or 
spontaneously regress, but both diseases are 
usually progressive and require treatment with 
immunosuppressive drugs.
HS/HHS
• Localized HS can be treated with wide-
margin surgical excision or palliative radiation 
therapy.
• Due to high metastatic risk, adjuvant 
chemotherapy (CCNU) is indicated following 
surgery or radiation for localized HS.
• Disseminated HS and HHS treated with 
chemotherapy (CCNU), corticosteroids, and 
other immunosuppressive drugs.
FPH/Feline HS
• If localized, surgical removal or radiation 
therapy can provide long-term control.
chemotherapy is indicated following surgery 
or radiation for localized feline HS.
• Disseminated FPH/HS typically treated 
with chemotherapy and corticosteroids.
FPLCH
T reated with corticosteroids and other 
immunosuppressive drugs.  MEDICATIONS
HS/HHS
Lomustine (CCNU)—dogs: 60–90 mg/m2 
q3 weeks; cats: 40–60 mg/ m2 q3–4 weeks.
CH/SH
• Prednisone/prednisolone—1–2 mg/kg/day 
continuously.
• Leflunomide—dogs: 3–4 mg/kg/day.
• Cyclosporine—dogs: 5 mg/kg q12–24h.
N/A
Lomustine can lead to severe myelosuppres-
sion and hepatotoxicity.
Doxorubicin, vincristine, Doxil®, paclitaxel, 
cyclophosphamide, mitoxantrone, dacarbazine, 
epirubicin, vinorelbine, and vinblastine have all 
been used for HS/HHS with marginal success.
  FOLLOW-UP
Bleeding due to thrombocytopenia.
Canine Cutaneous Histiocytoma
• Spontaneous regression is likely within 2–3 
months.
• If required, surgical removal is typically 
curative.
LCH/CH/SH
• Rarely imminently fatal.
• Cutaneous lesions may wax and wane or 
spontaneously regress, but are usually 
progressive and require treatment with 
immunomodulatory drugs or surgical 
excision (if localized).
• SH is associated with a poorer prognosis; 
dogs are often ill from the disease and relapses 
are common.
HS/HHS
• Localized HS—long-term ( >12 months) 
survival has been documented for dogs that 
undergo surgery/radiation therapy and 
• Disseminated HS—reported response rates 
to CCNU are 40–50% for median remission 
duration of 3–6 months.• HHS is associated with rapid progression 
and a grave prognosis (median 7 weeks) even 
with treatment.
FPH
An indolent cutaneous disease initially, but 
may spread internally and become life- 
threatening.
FPLCH
Aggressive disease course; most cats succumb 
to respiratory failure and illness due to other 
organ involvement.
SYNONYMS
N/A
• BMD = Bernese mountain dog.
• CH = cutaneous histiocytosis.
• FCR = flat-coated retriever.
• FPH = feline progressive histiocytosis.
• FPLCH = feline pulmonary Langerhans cell 
histiocytosis.
• HHS = hemophagocytic histiocytic 
sarcoma.
• HS = histiocytic sarcoma.
• LCH= Langerhans cell histiocytosis.
• SH = systemic histiocytosis.
Clifford CA, Skorupski KS. T umors of the 
skin, subcutis and soft tissue; histiocytic 
diseases. In: Henry CJ, Higginbotham ML, 
eds., Cancer Management in Small Animal 
Practice. St. Louis, MO: Saunders Elsevier, 
2010, pp. 326–330.
Moore, PF . A review of histiocytic diseases of 
dogs and cats. Vet Pathol 2014, 
51:167–184.
Moore PF , Affolter VK. Feline progressive 
histiocytosis. Vet Pathol 2006, 43:646–655.
Skorupski KA, Clifford CA, Paoloni MC, 
et al. CCNU for the treatment of dogs with 
histiocytic sarcoma. J Vet Intern Med 2007, 
21:121–126.
Authors  Sophie Aschenbroich, Christine 
Mullin, and Craig A. Clifford
Consulting Editor  Timothy M. Fan(continued)  Histiocytic Diseases—Dogs and Cats

652  Blackwell’s Five-Minute Veterinary Consult  
HHistiocytosis, Cutaneous
  BASICS
OVERVIEW
Skin diseases characterized by infiltration of 
histiocytic cells.
Histiocytoma
• Most common in dogs <3 years of age. 
• Boxers, dachshunds, cocker spaniels, Great 
Danes, Shetland sheepdogs, bull terriers. 
• Shar peis—Langerhans cell histiocytosis 
(LCH): multiple cutaneous histiocytoma 
syndrome.
Reactive Histiocytosis (RH)
• Cutaneous (cRH)—middle-aged to 
older dogs. • Systemic (sRH)—middle-aged 
dogs; male Bernese mountain dogs, 
Rottweilers, golden retrievers, Labrador 
retrievers.
Histiocytic Sarcoma (HS)
Middle-aged to older dogs—Bernese 
mountain dogs, flat-coated retrievers, 
Rottweilers, golden retrievers.
Feline Progressive Histiocytosis (fPH)
Middle-aged to older cats; female 
predisposition.
SIGNS
Solitary erythematous and/or ulcerated cutaneous 
nodule usually on head, extremities, and ears.
• Multiple histiocytomas; may persist for 
prolonged period or may never regress. 
• Lymphadenopathy with metastasis—affects 
lungs and other organs.
cRH
• Erythematous or ulcerated nodules or 
plaques affecting the face, nose, neck, trunk, 
extremities, footpads, perineum; no systemic 
involvement. • Depigmentation of mucous 
membranes and nasal planum (with 
ulceration).
sRH
• Similar to cRH but with systemic organ 
involvement. • Peripheral lymphadenopathy. 
• Stertor due to nasal mucosal infiltration. 
• Ocular manifestations.
HS
• Cutaneous lesions uncommon; subcutane-
ous nodules develop. • Systemic signs depend 
on organ system involved.
fPH
• Initial solitary skin nodule with slow 
progression to multifocal alopecic or ulcerated 
nodules and plaques; nonpruritic and nonpain -
ful. • Lesions wax and wane, do not regress on 
their own.  DIAGNOSIS
• Histiocytoma and RH—other causes of 
nodular lesions; solitary round cell tumors: 
plasmacytoma, mast cell tumor, epithelio-
tropic cutaneous T-cell lymphoma (CTCL) 
• With depigmentation or ulceration—
immune-mediated or neoplastic diseases.
Normal with cutaneous histiocytic diseases.
IMAGING
Chest radiographs/abdominal ultrasound—  
differentiate cRH from sRH; may provide 
evidence of metastasis: HS, disseminated HS, 
or fPH.
• Histopathology required for diagnosis of 
LCH, RH, HS, fPH, and nonregressing 
histiocytoma. • Fine-needle aspirates may be 
diagnostic for histiocytoma—cytology from 
lymph nodes or internal organs may provide 
evidence of sRH or HS.
• Top-heavy appearance; histiocytic cells invade 
dermis with occasional nests of cells in epidermis. 
• Cellular atypia uncommon; mitotic index often 
high. • Lymphocytic infiltrate associated with 
tumor regression. • Immunophenotype—CD1a, 
CD11c/CD18, E-cadherin positive.
• Similar to histiocytomas, with more 
anisokaryosis and multinucleated giant cells. 
• Immunophenotype same as histiocytoma.
RH
• Bottom-heavy appearance; cells invade mid to 
deep dermis, or extend into subcutis; composed 
primarily of lymphocytes and histiocytes; 
frequent vessel wall invasion. • Similar to 
inflamed nonepitheliotropic CTCL; definitive 
diagnosis requires T-cell receptor γ gene 
rearrangement analysis to detect clonal T-cell 
population. • Immunophenotype—CD1a, 
CD4, CD11c/CD18, CD90 positive. 
• Histopathology identical for cRH and sRH.
HS
• Sheets of large, pleomorphic, mononuclear 
cells; cellular and nuclear atypia with mitotic 
figures and giant cells. 
• Immunophenotype—CD1a, CD11c/
CD18 positive.
fPH
• Infiltration of dermis with well-differentiated 
histiocytic cells; occasionally extends to 
subcutis. • Epitheliotropism common; single 
cells or aggregates of histiocytic cells within 
epidermis. • Cellular and nuclear atypia 
increase with progression. • Immunophenotype—CD1a, CD11b/CD18 
positive, CD5 positive in 50% of cases.
  TREATMENT
• No treatment necessary; lesions usually 
regress within 3 months. • Surgical excision 
curative for persistent lesions.
HS
• Surgical excision of localized lesions 
recommended. • Variable response to medical 
therapy. • Poor prognosis—majority of 
patients survive a few months after diagnosis.
fPH
• Poor response to medical therapy. • Guarded 
prognosis—cats usually succumb to metasta-
sis beyond the skin.
• Poor response to medical therapy; short-
term improvement reported with lomustine. 
• Guarded prognosis—cutaneous lesions as 
well as metastatic lesions progress, with 50% 
of patients euthanized.
RH
• Clinical signs wax and wane and may not 
necessitate therapy. • cRH or sRH—variable 
prognosis: some dogs respond to long-term 
therapy. • 50–100% response rate to steroids. 
• Other drugs—azathioprine, modified 
cyclosporine, mycophenolate, leflunomide, and 
doxycycline/niacinamide. • Localized cutaneous 
lesions—topical tacrolimus or steroids.
See T reatment.
  FOLLOW-UP
Depends on disease.
• cRH = cutaneous RH. • CTCL = cutaneous 
T-cell lymphoma. • fPH = feline progressive 
histiocytosis. • HS = histiocytic sarcoma. 
• LCH = Langerhans cell histiocytosis. • RH = 
reactive histiocytosis. • sRH = systemic RH.
Moore PF . A review of histiocytic diseases of 
dogs and cats. Vet Pathol 2014, 51:167–184.
Author  Kathryn A. Rook
Contributing Editor  Alexander H. 
Werner Resnick

Canine and Feline, Seventh Edition  653
HHistoplasmosis
  BASICS
Systemic fungal infection caused by 
Histoplasma capsulatum .
• Soil‐borne dimorphic fungus; mycelial form 
grows best in bird manure or organically 
enriched soil. • Mycelium in the soil—
produces infectious spores (microconidia); 
inhaled into terminal airways. • Spores—
germinate in the lungs, develop into yeast form 
at mammalian body temperature, reproduce by 
budding. • Yeast are phagocytized by 
mononuclear phagocytes that distribute the 
organisms throughout the body. • Ingested 
organisms may directly infect intestinal tract. 
• Immune response—determines whether 
disease develops; affected animals often develop 
transient, asymptomatic infection.
• Cats—respiratory tract, musculoskeletal, 
hepatobiliary, spleen, skin, and lymphatics; 
gastrointestinal, ophthalmic, renal, and 
nervous systems less frequent. • Dogs—
gastrointestinal system, hepatobiliary, 
respiratory, spleen, and lymphatics; 
musculoskeletal, renal, ophthalmic, and 
reproductive systems less frequent.
GENETICS
N/A
Prevalence of clinically relevant histoplasmosis 
low in cats and dogs.
• Endemic areas—Ohio, Missouri, Mississippi, 
Tennessee, and St. Lawrence river basins. • Also 
Texas, southeastern United States, Great Lakes 
region, and California. • Has been isolated 
from the soil of 31 US states.
Species
N/A
• Cats—young (many <1 year of age); all 
ages can be infected. • Dogs—young to 
middle‐aged; all ages can be infected.
• Cats—females may be overrepresented. 
• Dogs—N/A.
SIGNS
Cat
• Insidious onset (days–weeks). • Anorexia, 
weight loss, and dyspnea. • Occasional cough. 
• Lameness. • Ocular discharge. • Diarrhea.Dogs
• Weight loss, depression, diarrhea with 
straining. • Coughing. • Dyspnea. • Exercise 
intolerance. • Lymphadenopathy. • Lameness 
and eye and skin changes less common.
Cats
• Fever to 104 °F (40 °C). • Increased 
respiratory effort, harsh lung sounds. 
• Mucous membranes pale. • Enlarged 
lymph nodes. • Lameness, ocular changes, 
and skin lesions possible.
Dogs
• Thin to emaciated. • Fever to 104 °F 
(40 °C). • Hepatosplenomegaly. • Mucous 
membranes pale. • Icterus and ascites 
possible. • Coughing and dyspnea, harsh 
lung sounds. • Ocular and skin lesions less 
common.
CAUSES
• Bird roosts where the soil is enriched with bird 
or bat droppings are high‐risk environments; 
old chicken coops and caves have been 
implicated. • Exposure to airborne dust 
contaminated with fungal spores (especially 
indoor cats). • Tissue samples from nearly half 
of stray dogs and cats from an endemic area 
were positive for Histoplasma ; many animals are 
infected but few develop clinical disease.
  DIAGNOSIS
Cats
• Dyspnea—differentiate from heart failure, 
feline asthma, lymphoma, other infectious 
pneumonia, pleural effusion. • Lameness—
trauma, neoplasia. • Ocular changes—
differentiate from lymphoma, toxoplasmosis, 
and feline infectious peritonitis.
Dogs
• Severe chronic diarrhea, weight loss, and 
anemia—consider lymphocytic plasmacytic 
or eosinophilic enteritis, protein intolerance, 
lymphoma or other intestinal neoplasia, 
chronic parasitism, and hypoadrenocorticism. 
• Hepatosplenomegaly and peripheral 
lymphadenopathy—consider lymphoma or 
other neoplasia. • Respiratory signs—
differentiate from infectious causes 
(distemper, bacterial, or other fungal 
pneumonia), chronic bronchitis, pleural 
effusion, heart failure, and pulmonary 
• Moderate to severe nonregenerative anemia. 
• Leukogram—usually normal; some have 
leukocytosis; leukopenia with bone marrow involvement. • Histoplasma  organisms—may 
be found in circulating neutrophils and 
monocytes; 2–4  μm round body with 
basophilic center and lighter halo. • Liver 
involvement—may see hyperbilirubinemia 
and high alanine aminotransferase (ALT) 
enzyme activity. • Panhypoproteinemia in 
dogs with severe intestinal histoplasmosis.
• Agar gel immunodiffusion (AGID) 
test—for antibodies; supports diagnosis; 
positive results indicate active disease; previous 
infections may produce false‐positive results; 
many animals with active disease are negative 
on serology. • Urine antigen test—highly 
sensitive and specific test for diagnosis in dogs 
and cats. • Coombs’ test—may be positive 
because antibodies to Histoplasma  can cross‐
react with red blood cells; caution before 
diagnosing immune‐mediated disease.
IMAGING
• Dogs—diffuse interstitial to nodular 
pneumonia, enlarged tracheobronchial lymph 
nodes; chronic lesions may be calcified, coin‐
like opacities that appear like metastatic 
tumors. • Cats—diffuse interstitial pulmonary 
pattern; calcification and tracheobronchial 
lymphadenopathy uncommon.
Abdominal Radiography 
and Ultrasonography
Dogs—hepatosplenomegaly, mesenteric 
lymphadenopathy, potentially ascites.
Bone Radiography
Cats and less often dogs—bone lesions 
predominantly osteolytic and usually distal to 
elbows and stifles.
• Identification of organisms on cytology, 
histopathology, or culture—definitive. • Tissue 
samples: ◦ Needle aspiration of enlarged lymph 
nodes, liver, and spleen. ◦ Rectal scrapings may 
be rich in organisms (yeast form packed in 
macrophages). ◦ Bone marrow or lung 
aspirates (when less invasive procedures are not 
diagnostic); tracheal washes inconsistent.
• Multifocal, granulomatous lesions in 
reticuloendothelial organs (e.g., spleen, liver, 
lymph nodes, lungs, and bone marrow).
• Dogs—gastrointestinal tract is primary site; 
enlarged tracheobronchial lymph nodes.
• Cats—predominantly respiratory lesions.
  TREATMENT
• Usually outpatient with oral itraconazole. 
• Inpatient with IV amphotericin B—dogs 
with severe intestinal disease and

654  Blackwell’s Five-Minute Veterinary Consult  
Hmalabsorption, dogs or cats with severe 
respiratory disease.
• Amphotericin B therapy—keep well 
hydrated to decrease potential for 
nephrotoxicity. • Emaciated animals with 
malabsorption—consider parenteral nutrition 
until intestinal disease sufficiently resolves. 
• Animals with severe dyspnea—oxygen 
ACTIVITY
Animals with dyspnea—reduce.
DIET
N/A
• Discuss possible areas of exposure in the 
home environment.
• Both pets and family members may have 
been exposed to the same source, but pet is 
not a hazard to the family.
Azole Antifungal Drugs
• No differences reported between 
itraconazole and fluconazole in survival, 
clinical remission, or disease relapse rates. 
• Duration of therapy depends on clinical 
response; minimum treatment 90 days.
• Dogs and cats—5 mg/kg PO q12h; with 
high‐fat meal. • Absorption of compounded 
itraconazole is inconsistent and these 
formulations are not recommended.
• May be preferred for animals with eye or 
nervous system involvement (penetrates the 
blood–brain barrier). • Injectable (5 mg/kg 
IV q12h) for animals unable to take oral form 
and high risk for amphotericin B.
Intravenous Amphotericin B
Dogs
• With severe intestinal disease and 
malabsorption—use until intestinal absorption 
improves, then start on itraconazole. • Patient 
must be well hydrated before starting 
treatment. • Usual dose—0.5–1.0 mg/kg IV 
q48h. ◦ Reconstitute in 5% dextrose and 
dilute for administration. ◦ Dilution in 
electrolyte solution may precipitate drug. 
◦ Patients with normal renal function—dilute 
in 60–120 mL 5% dextrose and give over 2 hours. ◦ Patients with renal compromise—
dilute in 0.5–1 L 5% dextrose and give over 
3–4 hours. • Liposomal amphotericin (Abelcet®) 
can reduce risk of renal toxicity.
Cats
• Use cautiously. • Usual dose—0.25 mg/kg 
IV in 5% dextrose over 3–4 hours q48h. 
• More sensitive to drug than dogs.
Amphotericin B—caution with azotemic 
patients (in life‐threatening situation, may 
still consider); monitor creatinine: elevation 
above normal or 20% greater than baseline 
considered significant.
• Corticosteroids—use with caution; may be 
useful in patients with severe pulmonary 
disease; dexamethasone 0.1 mg/kg IV q24h 
for 2–3 days. • Itraconazole and fluconazole—
hepatic toxicity; temporarily discontinue if 
patient becomes anorexic or if serum ALT 
activity >300 U/L; restart at half dose after 
appetite improves.
Itraconazole—can increase concentrations of 
cyclosporine, digoxin, and midazolam (P450 
inhibition).
N/A
  FOLLOW‐UP
• Serum ALT—with itraconazole treatment; 
check monthly or as needed. • Thoracic 
radiographs—with pulmonary involvement; 
check after 60 days of treatment and repeat 
monthly until infiltrates are clear or remaining 
lesions are static (likely scarring); continue 
treatment for 1 month after all signs of active 
disease resolved. • Urinary antigen levels 
sensitive for monitoring remission in cats.
• Avoid suspected areas of exposure (e.g., bird 
roosts). • Recovered dogs may be immune.
Recurrence possible.
• T reatment—duration usually 4–6 months; 
drugs are expensive; some dogs require longer 
therapy. • Prognosis—good for stable patients 
without severe dyspnea; influenced by severity 
of lung involvement and debility of patient. • Negative prognostic factors include Great 
Pyrenees breed, dyspnea, oxygen dependency, 
icterus/hyperbilirubinemia, palpable 
abdominal organomegaly, anemia, thrombo-
cytopenia, hypercalcemia, high serum alkaline 
phosphatase activity.
N/A
N/A
humans. • Avoid needlestick injury when 
collecting aspirates. • Infection can occur from 
cuts during necropsies on infected animals.
Azole drugs can be teratogenic, use with 
caution in pregnant animals.
Cunningham L, Cook A, Hanzlicek A, et al. 
Sensitivity and specificity of Histoplasma 
antigen detection by enzyme immunoassay. 
J Am Anim Hosp Assoc 2015, 51:306–310.
Hanzlicek AS, Meinkoth JH, Renschler JS, 
et al. Antigen concentrations as an indicator 
of clinical remission and disease relapse in 
cats with histoplasmosis. J Vet Intern Med 
2016, 30:1065–1073.
Lin Blache J, Ryan K, Arceneaux K. 
Histoplasmosis. Compend Contin Educ Vet 
2011, 33:E1–E10.
Schulman RL, McKiernan BC, Schaeffer DJ. 
Use of corticosteroids for treating dogs with 
airway obstruction secondary to hilar 
lymphadenopathy caused by chronic 
histoplasmosis: 16 cases (1979–1997). J Am 
Vet Med Assoc 1999, 214:1345–1448.
Wilson AG, KuKanich KS, Hanzlicek AS, 
et al. Clinical signs, treatment, and 
prognostic factors for dogs with 
histoplasmosis. J Am Vet Med Assoc 2018, 
252:201–209.
available onlineHistoplasmosis  (continued)

Canine and Feline, Seventh Edition  655
H  BASICS
OVERVIEW
• Nematode parasites of small intestine—dogs: 
Ancylostoma caninum , A. braziliense , Uncinaria 
stenocephala ; cats: A. tubaeforme , A. braziliense , 
U. stenocephala . • Eggs larvate, hatch, develop 
into third-stage larvae (L3) in environment; 
transmitted by ingestion of infective larvae in 
food, water, or transport hosts and by larval 
skin penetration; A. caninum  is transmitted via 
colostrum/milk to pups. •  Some L3 migrate 
through lungs, enter somatic tissue, and 
become dormant; pregnancy and removal of 
adults from intestine can reactivate these larvae; 
many ingested larvae remain in gastrointestinal 
(GI) tract and mature. •  Blood-sucking adults 
and fourth-stage larvae of A. caninum  and A. 
tubaeforme  cause blood-loss anemia and enteritis; 
leave bite sites with ongoing hemorrhage. 
• Disease severity: ◦ Peracute—neonates; 
results from transmammary infection. ◦ Acute 
disease—older pups. ◦ Acute, chronic 
compensatory—adults. ◦ Chronic noncom -
pensatory—immunosuppressed or debilitated 
dog. •  Uncinaria— of little clinical concern. 
• A. braziliense— major cause of cutaneous 
larval migrans (CLM) in humans. 
• Respiratory disease may result from larval 
migration in lungs.
• Peracute to acute disease (young 
animals); asymptomatic or chronic 
(mature animals). •  More severe clinical 
disease in dogs than cats.
SIGNS
• Pallor, melena, diarrhea, constipation, 
loss of condition, poor appetite, and/or dry 
cough. •  Sudden death.
• Poor body condition, ill-thrift, poor hair 
coat. •  Pallor. •  Erythematous, pruritic 
lesions, papules on feet (especially between 
toes). •  Shock—tachycardia, weak pulse, 
prolonged/absent capillary refill time.
• Neonatal animals at highest risk. •  Infected 
bitch or queen. •  Environmental contamination. 
• Concurrent enteric infections. 
  DIAGNOSIS
• Causes of anemia and hypovolemic/
hemorrhagic shock; trichuriasis. •  Ascariasis, coccidiosis, strongyloidosis—similar signs 
without  significant anemia. •  Physalopterosis—
melena, mild anemia.
• Eosinophilia. •  Anemia—normochromic, 
normocytic, regenerative; chronically 
microcytic, hypochromic (iron deficiency).
• Disease/death may occur prior to egg 
shedding. •  Fecal flotation with 
centrifugation—morulated strongylid eggs; 
minor size differences among species. •  Fecal 
ELISA—detects antigen from adult and 
immature worms, can detect prepatent 
infection. •  Necropsy of littermates with 
similar clinical signs.
• Gross—hookworms attached to small 
intestinal mucosa, multifocal hemorrhagic 
ulcerations (bite sites) on mucosa, blood 
in intestinal lumen. •  Microscopic—
eosinophilic enteritis.
  TREATMENT
• Peracute and severe acute cases treated as 
inpatients—anthelmintic, fluid therapy, 
blood transfusion, supplemental oxygen, 
symptomatic/supportive care as indicated. 
• Chronic compensatory cases—
anthelmintic, iron supplement.
Adulticide/Larvicide Anthelmintics
• Fenbendazole 50 mg/kg PO q24h for 3 
consecutive days (dogs). •  Milbemycin oxime 
0.5 mg/kg (dogs) or 2 mg/kg (cats) PO q30 
days. •  Emodepside 3 mg/kg/praziquantel 
12 mg/kg topically once (cats). •  Moxidectin 
0.17 mg/kg SC q6 months (dogs). •  Moxidectin 
2.5 mg/kg (dogs) or 1.0 mg/kg (cats)/
imidoclopramide 10 mg/kg, topically q30 
days. •  Ivermectin 24  μg/kg PO q30 days 
(cats).
Adulticide Activity (Label Dose unless 
Stated)
• Pyrantel pamoate (dogs) 10–20 mg/kg 
PO (cats: extra-label). •  Praziquantel/
pyrantel pamoate/febantel (dogs). 
• Praziquantel/pyrantel pamoate (cats). 
• Ivermectin/pyrantel pamoate or 
ivermectin/pyrantel pamoate/praziquantel 
(dogs). •  Selamectin 6 mg/kg topically q30 
days (cats).  FOLLOW-UP
Monitor fecal egg counts and hematocrit 
after treatment.
• Routine deworming does not eliminate 
dormant L3; eliminate intestinal stages and 
reactivated larvae in breeding bitch using 
fenbendazole (50 mg/kg/day PO from day 40 of 
gestation to day 14 of lactation) or ivermectin 
(0.5 mg/kg PO 4–9 days prior to whelping, 
again 10 days later). •  Begin biweekly 
anthelmintic treatment of pups at 2 weeks; 
continue until weaned, especially high-risk pups; 
treat monthly after weaning. •  T reat queen with 
adulticide/larvicide anthelmintic prior to 
breeding, after queening. •  Begin anthelmintic 
treatment of kittens at 3–4 weeks of age; treat 
monthly thereafter. •  Promptly remove, 
dispose of feces to prevent environmental 
contamination. •  Prevent hunting and ingestion 
of potential transport hosts.
• Puppies (and rarely adults) with peracute/acute 
A. caninum  infection may die despite treatment. 
• Early recognition, anthelmintic treatment, 
prompt treatment of anemia, nutritional support 
necessary for successful outcome. •  Anthelmintic 
treatment of adults can result in larval 
reactivation, repopulation of small intestine.
• Disease more acute in young, usually 
chronic in adults. •  T ransmission of 
A. caninum  from bitch to offspring results 
in high rate of infection in pups.
• All hookworms, especially A. braziliense , 
cause human CLM. •  A. caninum  larvae 
can cause visceral larva migrans or migrate 
to GI tract, causing abdominal pain and 
eosinophilia without becoming patent.
• CLM = cutaneous larva migrans.
• L3 = third-stage larvae.
• https://capcvet.org •  https://www.cdc.gov/
parasites/zoonotichookworm
Saunders, 2008, pp. 179–185.
Author  Matt Brewer and Katy A. Martin
Consulting Editor  Amie KoenigHookworms (Ancylostomiasis)

656  Blackwell’s Five-Minute Veterinary Consult  
HHorner’s Syndrome
  BASICS
OVERVIEW
• Sympathetic denervation to the eye. 
• Anatomic pathway very important. 
• Affects the ophthalmic and nervous systems 
• Idiopathic—one study suggests male golden 
retrievers 4–13 years of age at increased risk. 
Most of these localize to a postganglionic 
lesion. • Idiopathic—50–93% of Horner’s 
syndrome in dogs; 45% in cats.SIGNS
• Miosis. • Protruding third eyelid. • Ptosis 
(drooping) of upper eyelid. • Enophthalmos. 
• Other neurologic and non-neurologic signs 
dependent on the underlying cause.
  DIAGNOSIS
Anterior uveitis—intraocular pressure (IOP) 
usually low; aqueous flare present.
N/A
N/A
IMAGING
• See Table 1. • Thoracic radiographs—may 
reveal cause of injury to the sympathetic 
trunk (e.g., trauma or mediastinal tumor). 
• CT to image skull and middle ear. 
• MRI—may help identify brainstem lesion, 
retrobulbar mass, cervical spinal cord 
problem, or jugular groove lesions. 
• Ultrasonography—orbit; may reveal 
retrobulbar mass; jugular groove; may reveal 
jugular groove mass.
• See Table 1. • Cerebral spinal fluid (CSF) 
tap—identify brain and spinal cord 
inflammation. • Electromyography— look 
for brachial plexus denervation consistent 
with avulsion. • Pharmacologic testing—see 
Anisocoria.
  TREATMENT
T reat underlying disease.  MEDICATIONS
• Depends on underlying disease. 
• Idiopathic—none.
Do not use drugs that alter the autonomic 
nervous system prior to referral for lesion 
  FOLLOW-UP
• Depends on severity of underlying disease. 
• Idiopathic—may take up to 4 months for 
a partial or complete recovery.
• CN = cranial nerve. • CSF = cerebrospinal 
fluid. • FCE = fibrocartilaginous embolism. 
• IOP = intraocular pressure. • IVDH = 
intervertebral disc herniation.
anisocoria. In: Kirk’s Current Veterinary 
Therapy, 14th ed. St. Louis, MO: Saunders, 
2009, pp. 1168–1174.
Simpson KM, Williams DL, Cherubini GB. 
Neuropharmacological lesion localization in 
idiopathic Horner’s syndrome in Golden 
Retrievers and dogs of other breeds. Vet 
Ophthalmol 2015, 18(1):1–5.
Consulting Editor  Kathern E. MyrnaHypothalamus 
Brainstem/cervical cord  
T3–L3 spinal cord segmen ts 
and nerve roots 
Vagosympathetic trunk  
Cranial cervical ganglion  
Tympanic bulla  
Ophthalmic branch of  
trigeminal nerve 
Iris dilator muscles, periorbital  
smooth muscles, upper and 
3rd eyelid  First order neuron  
Second order
neuron/preganglionic
Third order neuron /
post-ganglionic  
Figure 1 .
Table 1
Summary of lesions resulting in Horner’s syndrome.
Lesion Location Causes Common Concurrent Neurologic Abnormalities Diagnostic Plan
Brainstem Neoplasia, encephalitis, vascular, 
traumaAltered mental status, ipsilateral hemiparesis, 
ipsilateral postural reaction deficitsMRI; CSF analysis
C1–T3 spinal cord IVDH, trauma, neoplasia, FCE Ipsilateral or bilateral paresis/plegia, ± reduced 
reflexes to thoracic limbs, normal mentationMRI preferred, myelogram also 
may show lesion. CSF analysis
T1–T3 nerve roots Brachial plexus avulsion, 
peripheral nerve tumor 
(lymphoma, nerve sheath tumor 
most common)Ipsilateral loss of thoracic limb reflexes, 
ipsilateral loss of cutaneous trunci, ipsilateral 
monoparesis/plegai, absent postural reactions 
in affected thoracic limb onlyMRI, electrodiagnostic testing
Sympathetic trunk, 
cranial cervical 
ganglionTrauma, iatrogenic following 
jugular venipuncture, 
mediastinal or thyroid neoplasiaPossibly laryngeal dysfunction Neck ultrasound, MRI, thoracic 
radiographs
Tympanic bulla Otitis media, polyp (cat), 
neoplasia, traumaIpsilateral vestibular disease, ipsilateral facial 
nerve paralysisMRI, CT, bulla radiographs, 
myringotomy
Retrobulbar Neoplasia, abscess, trauma None, or dysfunction of CN II, III, IV, and VI. MRI, orbital ultrasound

Canine and Feline, Seventh Edition  657
H  BASICS
• Deposition of urine or feces outside the 
litter box.
• Urine housesoiling (also called periuria) 
includes toileting, a behavior in which urine 
is found on horizontal surfaces outside the 
litter box, and urine marking, in which urine 
is sprayed on vertical (occasionally horizontal) 
surfaces as part of a ritualistic tail-up display.
• Fecal housesoiling includes both toileting, 
a behavior characterized by feces deposited 
outside the litter box, and fecal marking, 
called middening, characterized by feces 
deposited in prominent locations.
• Marking behavior serves a normal 
communicative function in cats, particularly 
in response to other cats inside or outside the 
home.
• Housesoiling will negatively impact the 
human–animal bond and can lead to 
relegation outside, rehoming, relinquishment, 
or euthanasia.
• Toileting—may be dissatisfaction with the 
litter box environment or preference for an 
alternative location or substrate, or may 
reflect an underlying pathophysiologic state 
such as a negative (pain) association with the 
litter box secondary to feline idiopathic 
cystitis (FIC) or feline lower urinary tract 
disease (FLUTD), uroliths, constipation, or 
orthopedic pain.
• Urine marking—a normal behavior 
observed in free-ranging and confined cats; 
significant individual differences exist in 
the propensity to urine mark in a given 
environment. Cat density is correlated to 
probability of urine marking. Cats who urine 
mark also commonly use a litter box for 
toileting (both urine and feces).
• Fecal marking (middening) is rarely 
observed; it should be a diagnosis of exclusion.
• Social or environmental stressors may 
contribute to housesoiling, primarily marking.
• Neurologic/musculoskeletal.
GENETICS
• Not specifically identified.
• Persians and Himalayans who exhibit 
toileting should be DNA tested for the 
genetic disorder polycystic kidney disease.
• Housesoiling is the most common 
behavioral problem for which cat owners 
seek veterinary advice and the second most common reason for relinquishment of cats 
to animal shelters.
• Toileting—in one survey, 11% of indoor 
cat owners reported toileting outside the litter 
box as a problem.
• Urine marking—exhibited by approximately 
10% of castrated male and 5% of ovariectomized 
female house cats.
Housesoiling may be more problematic where 
cats are restricted indoors.
Species
Cat
Housesoiling may occur in any breed, 
although Persians, Himalayans, and relatives 
are overrepresented in some studies.
Toileting can occur at any age. Marking 
behaviors are typically seen in cats >6 
months.
• Housesoiling can occur in either sex, intact 
or altered.
• Urine marking is more common in males 
(intact and neutered) than females (intact and 
neutered).
SIGNS
Identify the Affected Cat in a Multicat 
Household
• Direct observation—although if punished, 
cats may become secretive.
• Videotaping or video monitoring.
• Separate the cats to identify the culprit. 
Note that this protocol may alter the social 
milieu sufficiently to inhibit toileting 
behavior.
• Add a urine indicator. Administer the dye 
fluorescein (6 fluorescein test strips in a gel 
capsule PO or 10 mg/cat). Urine outside 
the litter box will fluoresce under a Wood’s 
light for approximately 24 hours. If negative, 
the test can be repeated on another cat. 
Negative results are common in households in 
which the frequency of urine housesoiling is 
low. Fluorescein may stain fabrics. If urine PH 
is alkaline, urine is more likely to fluoresce.
• Add a feces indicator. Small shavings of 
nontoxic crayons may be mixed into food, 
with different colors fed to each cat.
Identify the Locations of Housesoiling 
within the House
The owner should draw a diagram of the home 
layout, indicating the locations of urine and 
fecal housesoiling and locations of litter boxes. 
Location of housesoiling can provide insight 
into the type of housesoiling and etiology.Historical Findings
Toileting Behavior
• Abnormal pattern of urination 
(incontinence, polyuria, hematuria, 
stranguria, dysuria) suggests an underlying 
congenital or medical problem.
• History of straining to defecate; vocalizing 
or running away when defecating; hard, dry, 
or bulky feces suggest painful defecations.
• Painful elimination or increases in volume 
or frequency of elimination could lead to 
soiling, conditioned avoidance, and new 
location or surface preferences.
• History of polydipsia, anorexia, vomiting, 
or diarrhea suggests an underlying medical 
etiology.
Urine Marking
• History of conflict, aggression, or avoidance 
behavior between cats in a multicat 
household.
• Observation of the posture of spraying 
urine—the cat orients caudally to a vertical 
surface, stiffens its posture, raises and quivers its 
tail, and directs a small burst of urine caudally.
• Observation of urine marks on vertical 
surfaces or puddled at the bottom of a wall.
• Urine marks can be found on prominent 
furniture or other objects, or on new objects 
brought into the house.
• Horizontal urine marks may be found on 
clothing or bedding associated with a 
particular person, cat, or dog, or in response 
to visitors or novel objects.
Fecal Marking
Feces deposited on prominent, conspicuous 
• If strictly behavioral, physical examination 
will be normal.
• Apparently neutered males that urine mark 
should be examined for the presence of penile 
spines, indicating the presence of endogenous 
testosterone, or quantify serum testosterone.
CAUSES
• Any metabolic or GI condition that causes 
polyuria (e.g. diabetes mellitus), diarrhea, or 
• Lower urinary tract disease including 
interstitial cystitis (may be associated with 
environmental stressors).
• Urolithiasis.
• Feline immunodeficiency virus (FIV).
• Liver disease.
• CNS disease/cognitive dysfunction 
(senility).
• Iatrogenic—administration of fluids, 
corticosteroids, diuretics, laxatives.
• Musculoskeletal pain that makes entry to/
exit from the litter box or elimination Housesoiling—Cats

658  Blackwell’s Five-Minute Veterinary Consult  
Hpostures difficult can contribute to litter box 
aversion.
• Hormonal influences may contribute to 
urine marking.
• Inadequate cleaning of litter box.
• Inadequate number of boxes or locations 
(one box per cat plus one is recommended).
• Box located in remote or unpleasant 
surroundings or subject to interference by 
dogs or children.
• Inappropriate type of box—covered or 
uncovered, too small; or allows other cats, pet 
dogs, and young children to target the cat as 
it exits.
• Time factors—daily or weekly temporal 
patterns of toileting suggest an environmental 
cause; acute onset in a cat who has previously 
used the litter box suggests a medical or social 
problem.
• Substrate—unacceptable litter type; 
preference tests indicate that most cats prefer 
unscented, fine-grained (clumping) litter, but 
individual variability; coincident change in 
litter box habits with new litter type suggests 
an association; sudden shift from one substrate 
(e.g., litter) to an unusual substrate (e.g., 
porcelain sink) suggests a lower urinary tract 
disorder.
• Location—urination outside the litter 
box may suggest a location preference or 
social factors; urination in the vicinity of 
the litter box may suggest dissatisfaction 
with qualities of the litter box, including 
litter box hygiene.
• Social dynamics—consider social conflicts 
between cats at the time the problem started 
(e.g., addition of a new cat).
Marking
• Marking is associated with arousal, anxiety, 
or territorial behavior.
• The probability of urine marking is directly 
proportional to the number of cats in the 
• Marking can be a response to household 
disruption or another cat(s) in or outside the 
home; urine marks around windows and 
doors to the outside suggest a response to the 
presence of an outdoor cat.
• Urine marking grocery bags or new furniture 
suggests arousal in response to new stimuli.
Toileting
• Inadequate litter box hygiene.
• Litter box features (litter type or scent, box 
size or style).
• Male.
• Sexually intact.
• History of urine marking by a parent.  DIAGNOSIS
• Must identify if a medical problem 
underlies the behavioral problem.
• If behavioral, must differentiate toileting 
from urine/fecal marking.
Usually normal when urine marking and 
toileting are strictly behavioral; urinalysis 
via cystocentesis is the minimum database 
in any cat with toileting behavior; collect 
serial samples from cats whose behavioral 
signs wax and wane; CBC and biochemistry 
are recommended prior to administration 
of medication and to evaluate medical 
status.
Cats with refractory toileting behavior or 
progressive signs should be tested for 
hyperthyroidism, FeLV, and FIV.
IMAGING
Abdominal ultrasonography, abdominal 
radiographs, and contrast studies if indicated 
to rule out urolithiasis and medical causes for 
toileting behavior.
Helpful historical information—map of the 
house with litter boxes and urine/fecal 
housesoiling identified; behavioral diary 
with daily frequency of urinations/
defecations inside each litter box and outside 
the litter boxes. Requires daily household 
None, unless an underlying medical etiology.
  TREATMENT
• Use environmental and behavioral therapies 
before or concomitant with pharmacologic 
• The environment for indoor cats should 
include safe resting places, separated and 
plentiful resources, and positive and 
predictable human–cat interactions.
• Restrict the cat from rooms or areas in 
which housesoiling occurs.
• For immediate management and in cases of 
agonistic relationships between cats in a 
multicat household, it may be necessary to 
confine the cat to one room in the owner’s 
absence. Provide a litter box (see specifica-
tions below), water, food, and resting sites. 
The cat can be let out of the room when the 
owner returns and is available for strict 
supervision. Initiate other, more permanent 
treatments.• Clean urine “accidents” with an enzymatic 
cleaner specific for this purpose.
• Scoop out litter boxes daily. Clean out and 
wash litter box and refill regularly.
• Avoid deodorizers, scented litters, or 
other strong odors in the vicinity of the 
litter box.
• Move food bowls away from litter boxes.
• Provide one litter box per cat, plus one, 
distributed in more than one location; 
positioned away from high traffic or noisy 
areas and with adequate opportunity for entry 
and exit to avoid conflict with other pets.
• If the litter box is covered, provide an 
additional large, plain, uncovered litter box 
filled with unscented, fine-grained, clumping 
litter, with no liner, and quantify cat use in a 
behavioral diary.
• Additional boxes may be provided (“litter 
box buffet”) to determine preference for litter 
box type and substrate. Insure box is large 
enough for cat’s needs for elimination and 
scratching.
• If one site in the home is preferred for 
toileting urination, place another litter box 
over this site. After it is in regular use, move 
very gradually each day to a site more 
acceptable to the owner.
• If there are signs that the cat is marking in 
response to cats outside the home, use 
mechanical or olfactory products to deter 
outside animals, or trap and remove.
• Reduce cat numbers to lessen conflicts if 
possible.
• Synthetic feline F3 facial pheromone 
(Feliway® Classic) is commercially available as 
a treatment for urine marking. The product is 
sprayed on marked locations or diffused in 
the environment. For intraspecific social 
conflict, consider use of feline maternal-
appeasing pheromone diffuser (Feliway 
Multi-cat or Feliway Friends).
• Litter box management, as described 
above, has been shown to decrease urine 
marking.
• Pharmacotherapy plays an important role 
in the control of urine marking.
ACTIVITY
Opportunities for active play that incorporate 
behavioral patterns of predatory stalking and 
pouncing should be provided daily.
DIET
No specific diet unless underlying medical 
etiology, such as urolithiasis or constipation. 
Consider use of urinary stress diets for stress- 
related cystitis.
• Cats do not housesoil to be spiteful.
• Scolding and punishment are contra -
indicated—they may increase cat anxiety and 
avoidance or fear of the owner.Housesoiling—Cats  (continued)

Canine and Feline, Seventh Edition  659
H• Understanding the underlying motivation 
for housesoiling is critical for treatment 
success.
• Creating a predictable environment will 
decrease anxiety and arousal that may 
contribute to housesoiling.
• Work to resolve cat conflicts within the 
home (see Aggression, Intercat Aggression).
• Meet the cat’s behavioral needs for play, 
sufficient resources, and safe elevated 
resting sites.
Castration reduces urine marking in up to 
90% of males and 95% of females.
Toileting
Psychotropic medication not usually 
indicated, except in treatment-resistant cases 
or when associated with generalized anxiety 
or heightened arousal.
• Medication to decrease arousal is often 
needed for treatment success.
• Drugs from a number of drug classes may 
be used. All have the general effect of 
decreasing arousal and anxiety. Side effects 
can be sedation and/or altered social behavior 
(see Table 1). Drugs commonly used include 
fluoxetine, paroxetine, clomipramine, 
amitriptyline, buspirone.
Medication may be needed to decrease the 
arousal that drives this behavior.
• Benzodiazepines—use cautiously or avoid 
because of rare cases of fatal idiopathic 
hepatic necrosis in cats receiving oral 
diazepam.
• T ricyclic antidepressants—cats with a history 
of cardiac conduction disturbances, urinary or 
fecal retention, megacolon, lower urinary tract 
blockages, seizures, and glaucoma.
All drugs listed are extra-label. Inform the 
client of extra-label use and potential side 
effects; document the discussion in the 
medical record or use a release form. Start 
psychotropic drugs when the owner is present 
to monitor the patient.
Do not use monoamine oxidase inhibitors 
(e.g., selegiline) concurrently with tricyclic 
antidepressants (TCAs) or selective serotonin 
reuptake inhibitors (SSRIs).
• Synthetic progestins—the risk of serious 
side effects, including blood dyscrasias, 
pyometra, mammary hyperplasia, mammary 
carcinoma, diabetes mellitus, and obesity, has 
diminished their once-common use.
• Pheromone therapy (Feliway Classic) may 
reduce urine spraying.
• l-theanine (Anxitane®) or alpha-casozepine 
(Zylkene®) may reduce cat anxiety.
• l-tryptophan and alpha-casozepine supple -
mented diets (Multifunction Urinary + Calm 
Diet, Royal Canin, Hill’s® Prescription Diet®  
c/d® Multicare Stress) may reduce cat anxiety 
and urine housesoiling.
  FOLLOW-UP
• Regular follow-up is essential.
• The owner should keep a daily log of 
elimination patterns so that treatment success 
can be evaluated and appropriate adjust -
ments can be made. Number the litter boxes 
and request that client count and record the 
number of urinations/defecations in each box 
and outside the litter boxes each day.
• For marking behavior, after 2 months of 
successful medication management, medication 
might be withdrawn gradually over 2 weeks. 
However, if the social features that underlie the 
behavior are still present, medication may need 
to be continued for treatment success.
• For medication monitoring, an annual CBC, 
chemistry profile, urinalysis, and physical 
examination are recommended as a minimum.PREVENTION/AVOIDANCE
• Neuter cats.
• Restrict cat numbers to decrease the 
probability of urine marking.
• Counsel clients on appropriate litter box 
selection, location, and hygiene.
• Veterinary practitioners should inquire 
about housesoiling at each veterinary visit. 
Early identification and treatment optimize 
Client expectations must be realistic. 
Immediate control of a longstanding problem 
of housesoiling is unlikely; the goal is gradual 
improvement over time.
• Prognosis for improvement is good if 
underlying etiology is identified and managed.
• Housesoiling is destructive to household 
belongings and erosive to the human–animal 
bond, which can lead to abandonment, 
relegation outside, relinquishment, and 
euthanasia.
Aggression between cats may be associated 
with urine marking.
• Older cats might find litter box access 
difficult and seek alternative locations. 
Low-rise litter boxes in accessible areas can 
provide better access for these cats.
• Failure to use the litter box could be 
associated with age-related cognitive decline.
Pregnant women should avoid or take 
appropriate precautions when cleaning cat 
feces because of the risk of toxoplasmosis.
TCAs are contraindicated in animals used for 
breeding.
SYNONYMS
• General—feline housesoiling.
• Urine—feline inappropriate elimination, 
urine marking, urine spraying, periuria.
Table 1
Drugs and dosages used to manage feline urine marking.
Drug Drug Class Oral Dosage in Cats Frequency Side Effects (Usually Transient)
Clomipramine TCA 0.25–1.0 mg/kg q24h Sleepiness
Amitriptyline TCA 0.25–1.0 mg/kg q24h Sleepiness
Buspirone Azapirone 0.5–1.0 mg/kg q12h GI tract side effects (rare)(continued)  Housesoiling—Cats

660  Blackwell’s Five-Minute Veterinary Consult  
H• Feces—feline inappropriate defecation, 
fecal marking, middening.
SEE ALSO
• Aggression, Intercat Aggression.
• FLUTD = feline lower urinary tract 
disease.
inhibitor.• TCA = tricyclic antidepressant.
practice-guidelines/house-soiling
• https://indoorpet.osu.edu/cats/
problem-solving
de Souza Dantas LM. Vertical or horizontal? 
Diagnosing and treating cats who urinate 
outside the box. Vet Clin Small Anim 2018; 
48:403–417.
change unwanted ones. New York: 
Houghton Mifflin Harcourt.Landsberg G. Feline housesoiling. In: 
281–295.
Neilson JC. House soiling by cats. In: Horwitz 
DF , Mills D, eds. BSAVA Manual of Canine 
and Feline Behavioural Medicine, 2nd ed. 
Gloucester: BSAVA, 2009, pp. 117–126.
Sherman
available onlineHousesoiling—Cats  (continued)

Canine and Feline, Seventh Edition  661
HHousesoiling—Dogs
  BASICS
Urination and/or defecation, for elimination 
or marking of territory, in locations that 
owners consider inappropriate.
• Improper or incomplete housetraining. 
• Submissive or excitement urination. 
• Marking behavior, due to territoriality, 
anxiety, testosterone influence. • Anxiety. 
• Cognitive dysfunction.
Behavioral—shelter relinquishment, 
euthanasia, or rehoming.
GENETICS
Some breeds appear to be more easily 
housetrained than others.
• Approximately 15%. • Almost 20% of 
owners relinquishing a dog to a shelter did so 
because it soiled in the house. • 37% of 
owners who reported talking to their 
veterinarian about a behavior problem reported 
housesoiling. • Housesoiling is a common 
reason to see a veterinary behaviorist.
None described.
Species
Dog
Potential genetic breed predisposition for ease 
of housetraining and submissive or  excite­
ment urination. Dogs obtained from a 
commercial breeding establishment are more 
likely to urinate vertically or submissively 
urinate than those obtained from a 
noncommercial breeder.
• Inappropriate elimination due to improper 
or incomplete housetraining, primarily in 
younger dogs. • Submissive and excitement 
urination, primarily in younger dogs. • Urine 
marking begins as the dog reaches sexual 
maturity. • Housesoiling is a common 
complaint from owners of elderly dogs.
The incidence of inappropriate elimination, 
including marking, in intact male dogs is 
almost 60% higher than in castrated male 
dogs and intact or spayed female dogs.
SIGNS
• Inappropriate elimination is the most 
common individual reason for shelter 
relinquishment. • Proper housetraining must 
be discussed with clients. • Housesoiling can 
be associated with medical problems.Historical Findings
• History of urination and/or defecation in 
inappropriate areas. • May be associated with 
signs of other behavioral disorders (such as 
separation anxiety). • May be associated with 
lack of time or knowledge to properly housetrain. 
• May be associated with punishment. • A 
complete history will help determine potential 
triggers, including when, where, and how 
frequently the elimination occurs, and reliability 
of outdoor elimination training.
• If examination findings and laboratory results 
are normal, housesoiling is more likely due to a 
behavioral cause. • There may have been an 
inciting medical cause that has been resolved but 
the animal continues to eliminate inappropriately.
CAUSES
Canine inappropriate elimination can be due 
to a primary behavioral problem or secondary 
to/concurrent with a medical disorder. Medical 
causes should be ruled out if a previously 
housetrained dog begins to soil, in dogs that 
are refractory to training, and when volume or 
frequency of elimination is increased.
• Lack of, improper, or incomplete house­
training. • Marking behavior. • Submissive 
urination. • Excitement urination. 
• Separation anxiety. • Cognitive dysfunction 
syndrome. • Noise phobia. • Fear induced. 
• Psychogenic polydipsia/polyuria.
Degenerative
• Osteoarthritis. • Renal failure. • Neuromuscular.
Anatomic
Ectopic ureters
Metabolic/Endocrine
• Incontinence. • Diabetes mellitus. 
• Diabetes insipidus. • Hepatic insufficiency. 
• Hyperadrenocorticism. • Hypoadreno­
corticism. • Neurologic.
• Genitourinary neoplasia. • Neurologic. 
• Other neoplastic diseases causing weakness.
Infectious/Inflammatory
• Urinary tract infection or inflammation. 
• Crystalluria with cystitis. • Inflammatory bowel 
disorder. • Pancreatic disease. • Intestinal parasites.
• Intact male. • Greater number of hours 
worked. • Concurrent behavioral problem, such 
as separation anxiety. • Owners unable to 
properly housetrain. • Owner using punishment 
or aversive training methods.
  DIAGNOSIS
Differentiate behavioral causes of 
inappropriate elimination from medical 
causes (see Causes) with a proper workup.CBC/BIOCHEMISTRY/URINALYSIS
Indicated to rule out medical causes.
IMAGING
Not indicated except to diagnose or rule out 
medical causes.
• Complete behavioral and medical history, 
including household layout and locations 
soiled. • Videorecording when the owner is 
present to view household interactions with 
the dog. • Journal to monitor potential causal 
factors, as well as to monitor improvement of 
the problem. • Videorecording when the 
owner is gone from the home to rule in/out 
separation anxiety or other anxiety disorders.
None for behavioral causes.
  TREATMENT
Appropriate measures to assure continued 
good health of the dog.
ACTIVITY
• Take dog outside often on a schedule to 
ensure enough access to eliminate outside, or 
provide acceptable access to the outside, e.g., via 
a dog door if the dog is trained properly. 
• Increase activity level to potentially help in the 
treatment of other problem behaviors, as well as 
to improve the dog’s mental and physical health.
DIET
• If the dog is inappropriately eliminating 
stool, feeding scheduled meals may help to 
maintain the dog on a schedule of elimination. 
• Feeding a diet of higher caloric density may 
help decrease the urge to defecate as frequently. 
• Water should not be withheld.
• Counsel the owner as to the cause(s) of the 
inappropriate elimination, as well as potential 
long­term management of the problem. • T reat 
underlying/contributing medical problems. 
• T reat other underlying/contributing 
behavioral problems. • Counsel owners on 
proper housetraining techniques that focus on 
reinforcing desirable and preventing undesirable 
behavior through supervision and confinement/
safe haven training. • Counsel owners not to 
use punishment ­based or aversive training 
methods—punishment creates fear, anxiety, and 
stress, which can increase housesoiling. • Do 
not use punishment to housetrain a dog, such as 
rubbing its nose in the soiled area, or verbally or 
physically reprimanding. • Clean the soiled 
areas with an enzymatic cleaner to help 
eliminate any odor that may attract the dog to 
eliminate there again; if the soiled object is a 
piece of clothing or other smaller cloth object, 
such as a throw rug, wash it. • Change the

662  Blackwell’s Five-Minute Veterinary Consult  
Hsignificance of the soiled area, such as by feeding 
the dog in the area.
Incomplete Housetraining
• Supervise the dog at all times. Monitor for 
pre­elimination signs to immediately take to the 
appropriate site. • If not supervised, keep 
confined to an area where the dog will not 
eliminate or where an elimination site is offered 
(indoor elimination area); confinement areas 
should be in a room, behind a barricade (safety 
gate), or a crate or pen where the dog is 
comfortably housed (safe haven; see Puppy 
Behavior Problems); do not confine to an area 
that causes panic, destruction, and/or injury to 
the dog. • In some cases, tethering the dog to 
owners or nearby allows better supervision; 
never tether without supervision. • Take the 
dog outside frequently to eliminate; schedule 
outdoor times to meet the frequency and timing 
of elimination. • Accompany the pet to the 
appropriate elimination site and immediately 
reward elimination. • Use a consistent “key 
phrase” to help associate the act with the 
location and timing of elimination. • Feed on a 
set schedule, with water always available.
Submissive or Excitement Urination
• Do not punish the behavior, as this will 
contribute to further fear and conflict. 
• People should ignore the dog when they 
enter the house (no verbal or physical inter­
actions or eye contact). • The dog should go 
outside to urinate before greeting. • The dog 
should be greeted in a nonconfrontational and 
quiet manner; do not lean over the dog or 
institute interactive play at the time of 
greeting. • Tossing treats or a toy or teaching 
an alternate behavior at homecoming such as 
“sit” may change the dog’s greeting response.
Urine Marking Behavior
• Educate owners on effectiveness of neutering 
to decrease urine marking. • Determine all 
triggers to the behavior, including anxiety ­
provoking stimuli. • Address those triggers 
with desensitization and counter ­conditioning 
and/or avoidance of the trigger where 
appropriate. • Prevent access to the preferred 
marking locations. • Medications may be 
indicated to treat underlying anxiety disorder.
Neutering intact male dogs decreases urine 
marking rapidly in 30% of dogs, with a 
gradual decline in 20% of dogs, and no 
change in 50%. The results are the same 
regardless of age of neutering.
• Negligible effect in animals if displaying 
submissive or excitement urination; not 
indicated unless anxiety is part of the problem 
behavior. • If urine marking or inappropriate elimination is anxiety induced, medications 
may be helpful, in conjunction with behavior 
modification. • Selective serotonin reuptake 
(TCAs)/anti ­anxiety medications, or other 
anti­anxiety medications may be helpful, 
especially with underlying anxiety—SSRI: 
fluoxetine at 1–2 mg/kg PO q24h; TCA: 
clomipramine at 1–3 mg/kg PO q12h. • For 
SSRIs and TCAs, the full onset of action can 
be 4–6 weeks after initiation of treatment; 
inform owners of time required for response 
to be noted. • Side effects of SSRIs and TCAs 
can include nausea, vomiting, diarrhea, and 
lethargy. • Additional side effects of TCAs 
can include potentiation of seizure activity.
• Medication without concurrent behavior 
modification. • T ricyclic antianxiety medications 
are contraindicated in seizures and cardiac disease, 
and may interfere with thyroid medications.
Based on drug chosen.
Do not use an SSRI and TCA together or in 
conjunction with a monoamine oxidase 
(MAO) inhibitor or opioid.
Pheromones, or supplements containing 
alpha ­casozepine, l ­theanine, or a calming 
probiotic may help to decrease anxiety.
  FOLLOW-UP
Monitor with owner by follow ­up visits or 
telephone calls. The owner should keep a 
journal of incidents, inciting factors, and 
treatments instituted to have an objective 
view of improvement.
• Properly housetrain. • Neuter male dogs. 
• Monitor for signs and treat any underlying 
medical condition. • T reat any underlying 
behavioral condition.
Recurrence if owner relapses in treatment, 
perhaps pet relinquishment.
• Prognosis for any behavioral problem is 
highly dependent on an owner’s ability and 
willingness to follow guidance—the following 
estimations of prognosis are based on the 
owner’s ability and commitment to follow 
instructions. • Prognosis for decreasing 
submissive and excitement urination is good. 
• Prognosis for managing incomplete house­
training is good. • Prognosis for marking in 
previously intact male: 50% improve (30% 
quickly, 20% more slowly) with neutering, 
even without complementary behavior modification. • Prognosis for managing urine 
marking in spayed or neutered dogs is good if 
the triggers are identified and managed with 
avoidance or other forms of behavior 
modification. • Some animals with a medical 
cause of inappropriate elimination will still 
eliminate inappropriately after the medical 
cause has been treated due to learning (e.g., 
self­reinforcing, new location preferences).
• Puppies are more likely to present for lack 
of or incomplete housetraining, as well as for 
submissive and excitement urination. 
• Cognitive dysfunction becomes more likely 
as the dog ages.
Low unless potentially zoonotic organisms in 
urine or feces.
SYNONYMS
• Inappropriate defecation. • Inappropriate 
elimination. • Inappropriate urination. 
• Urine marking.
SEE ALSO
• Submissive and Excitement Urination—Dogs.
• SSRI = selected serotonin reuptake inhibitor.
• https://www.dacvb.org • https://avsab.org
Col R, Day C, Phillips CJC. An 
epidemiological analysis of dog behavior 
problems presented to an Australian 
behavior clinic, with associated risk factors. 
J Vet Behav 2016, 15:1–11.
Horwitz D, ed. Blackwell’s Five ­Minute 
Canine and Feline Behavior, 2nd ed. Ames, 
IA: Wiley ­Blackwell, 2018, pp. 655–667.
Horwitz DF , Ciribassi J, Dale S, eds. Decoding 
Your Dog: The Ultimate Experts Explain 
Common Dog Behaviors and Reveal How to 
Prevent or Change Unwanted Ones. Boston, 
MA: Houghton Mifflin Harcourt, 2014.
Handbook of Behavior Problems of the 
Dog and Cat, 3rd ed. Philadelphia, PA: 
Author  Melissa J. Bain
available onlineHousesoiling—Dogs  (continued)

Canine and Feline, Seventh Edition  663
H  BASICS
• Abnormal dilation of the ventricular system 
within the cranium.
• May be symmetric or asymmetric.
• May involve the entire ventricular system or 
partial elements secondary to underlying cause.
• Obstructive—cerebrospinal fluid (CSF) 
accumulates in front of an obstruction along 
the normal CSF circulatory pattern 
(noncommunicating) or at its resorption site by 
the meningeal arachnoid villi (communicating); 
depending on the balance between production 
of CSF (which is constant and independent of 
intracranial pressure [ICP]) and the capacity for 
absorption of CSF , ICP may be high or normal; 
clinical signs may be noted in either case.
• Congenital obstruction—primary 
obstructive hydrocephalus; most common site 
is at the level of the mesencephalic aqueduct 
due to fusion of the rostral colliculi; prenatal 
infections (especially parainfluenza virus) may 
cause aqueductal stenosis with subsequent 
hydrocephalus; may result in considerable 
disruption of the architecture of the brain; 
diffuse ventricular enlargement may also 
suggest congenital ventricular dilation or 
obstruction at the level of the lateral apertures 
or foramen magnum; it is not uncommon to 
have asymmetric ventricular enlargement.
• Acquired obstruction—secondary obstructive 
hydrocephalus; sites include the interventricular 
foramina, mesencephalic aqueduct, or lateral 
apertures of the fourth ventricle.
• Overproduction of CSF (communicating)—  
rare; caused, e.g., by a choroid plexus tumor.
• “Compensatory hydrocephalus”—condi-
tion wherein CSF fills the space where the 
neural parenchyma was destroyed; not true 
hydrocephalus; terminology obsolete 
(hydrocephalus ex vacuo).
• External hydrocephalus—condition where 
CSF accumulates on the surface of the brain.
• Clinical signs of neurologic dysfunction 
result from damage to neural parenchyma, 
loss of neurons, and abnormal neuronal 
function.
• May also be associated with abnormalities 
in the spinal cord such as syringohydromyelia.
Nervous system.
GENETICS
Siamese cats—autosomal recessive.
Unknown
Species
• Congenital—small and brachycephalic 
dogs: bulldogs, Chihuahuas, Maltese, 
Pomeranians, toy poodles, Yorkshire terriers, 
Lhasa apsos, Cairn terriers, Boston terriers, 
pug dogs, and Pekingese.
• Inherited—Siamese cats and Yorkshire 
terriers; high incidence of clinically 
asymptomatic ventriculomegaly in normal 
adult beagles.
• Acquired—any breed of cat or dog.
• Congenital—usually becomes apparent at a 
few weeks up to 1 year of age; acute onset of 
signs can occur in dogs with previously 
undiagnosed congenital hydrocephalus; exact 
cause of this decompensation is uncertain.
• Acquired—any age.
None
SIGNS
• Congenital—may occur without clinical 
signs, especially in dogs of toy breeds; other 
malformations or anomalies of the CNS may 
be noted (e.g., malformations of the 
cerebellum or syringomyelia), which may 
further contribute to the constellation of signs.
• Acquired—signs attributable to the 
underlying disease may be as or more 
prominent than the signs attributable to the 
hydrocephalus.
• Severity of the clinical signs may not 
correspond to the degree of ventricular 
• Behavioral—decreased awareness; lack  
of or loss of training ability (including 
housetraining); excessive sleepiness; 
vocalization; sometimes hyperexcitability.
• Visual deficits including blindness.
• Seizures—may be noted.
• Head—may appear large and dome-
shaped with an exaggerated “stop”; open 
sutures and/or persistent fontanelles often 
present, but these may be present without 
hydrocephalus and vice versa; bilaterally 
divergent strabismus in some dogs with 
severe congenital hydrocephalus: due to 
malformation of the orbit or to brainstem 
• Signs may be acute or gradual in onset, and 
may be static or progressive.
• A wide variety of signs of brain dysfunction 
can occur.
• Cerebral disease—abnormal behavior 
(obtundation and drowsiness), cortical blind  ness 
(loss of vision with normal eyes and pupillary 
light reflexes), inappropriate vocalization, 
sometimes hyperexcitable, circling.• Gait abnormalities—incoordination, ataxia, 
and decreased postural reactions.
• Seizures—may occur.
• Congenital form—malformation of the 
orbit during growth may result in a 
ventrolateral strabismus with normal 
oculocephalic movements; oculocephalic 
movements may be abnormal if brainstem 
dysfunction is the cause of strabismus.
• Severely increased ICP—stupor or coma, 
pinpoint or dilated fixed pupils, loss of 
normal oculocephalic movements 
(physiologic nystagmus), abnormal 
respiratory patterns, decerebrate posture; may 
lead to fatal tentorial herniation.
• Severity of clinical signs may not correlate 
with ventricular size, although there is a 
tendency for worse clinical signs with greater 
enlargement of the ventricles.
CAUSES
• Congenital—numerous congenital 
malformations cause obstruction of the 
ventricular system and result in hydrocephalus; 
heritable malformation, prenatal infection 
(e.g., dogs: parainfluenza virus; cats: 
coronavirus), exposure to teratogens, brain 
hemorrhage secondary to dystocia, nutritional 
deficiency (vitamin A), other.
• Acquired—tumors, abscesses, and 
inflammatory diseases (including 
inflammation resulting from hemorrhage 
caused by traumatic injuries or other causes of 
bleeding).
Animals with compensated hydrocephalus 
may decompensate in the face of an insult 
such as infection or trauma, resulting in 
development of clinical signs.
  DIAGNOSIS
• Other congenital brain anomalies.
• Metabolic or toxic diseases resulting in 
cerebral dysfunction.
• Brain mass lesions or infectious diseases 
resulting in high ICP (hydrocephalus may 
coexist).
• T raumatic injury to the brain (hydro -
cephalus may coexist).
IMAGING
• Skull radiography (congenital)—enlarged 
domed cranium with open sutures and 
persistent fontanelles; cranial vault may have 
a ground-glass appearance; also may reveal 
calvarial thinning.
• CT and MRI—provide definite diagnosis.
• Ultrasonography through fontanelles may 
reveal enlarged ventricles.Hydrocephalus

664  Blackwell’s Five-Minute Veterinary Consult  
HDIAGNOSTIC PROCEDURES
• CSF—use caution when collecting sample if 
patient has high ICP (may lead to fatal brain 
herniation through the foramen magnum 
and/or beneath the tentorium cerebelli); 
composition normal if no other intracranial 
disease (e.g., neoplasia, inflammation), but 
frequently abnormal when acquired 
• Electroencephalography (EEG)—congenital: 
usually characteristic, including hyper -
synchrony, high amplitude (25–300  μV), and 
low frequency (1–7 Hz); acquired: varies.
• Brain—may be large with loss of the 
normal pattern of sulci and gyri; may see 
distortion of the parenchyma, including 
thinning of the cerebral cortex, rupture of the 
septum pellucidum, and atrophy of other 
adjacent structures; with severe disease, brain 
herniation may occur, either of the cerebrum 
and midbrain under the tentorium cerebelli 
or of the cerebellum and caudal medulla 
oblongata through the foramen magnum.
• Ventricular system—mildly to severely 
distended (either entirely or only the part 
rostral to the obstructive lesion); with 
noncommunicating form, narrowing or 
blockage of the ventricular system due to 
inflammation or mass lesions.
  TREATMENT
• Inpatient—intensive care for patients with 
severe signs or when undergoing surgical 
therapy.
• Outpatient—patients with mild to 
moderate signs that can be treated medically.
Prevent secondary complications of recum-
bency for stuporous or comatose patients—
avoid pressure sores; drying eyes; hypostatic 
lung congestion.
Advise client to observe for deterioration in 
mental alertness, vision, and behavior, which 
may signal worsening of the problem.
• Surgical shunting of the CSF from the 
ventricles to the peritoneal cavity or right 
atrium—definitive treatment.
• Surgery should be considered only when 
medical management is ineffective or results 
in adverse side effects.
• Complications—shunt blockage occurs in up 
to 50% of patients; infection is less common; 
shunt revision commonly needed; overshunting may result in severe and potentially fatal 
complications (collapse of the cerebral mantle).
• Clinical signs may not resolve completely; 
residual signs usually indicate irreversible 
brain damage.
• Surgery for a brain tumor or other mass 
lesion—consider if it is the underlying cause.
• Reduce CSF production—data on the 
efficacy of corticosteroids in reducing CSF 
production are conflicting, but beneficial 
clinical effects usually are seen (prednisone 
0.25–0.5 mg/kg PO q12h or dexamethasone 
0.1 mg/kg PO q12h); should be tapered to an 
alternate-day regimen and the dose lowered as 
far as possible.
 ◦Carbonic anhydrase inhibitors: 
acetazolamide (10 mg/kg PO q8h) with or 
without furosemide (1 mg/kg q24h); 
electrolytes must be monitored frequently; 
long-term use is unlikely to be beneficial 
and may lead to adverse consequences.
 ◦Omeprazole has been reported to reduce 
CSF production in normal dogs in an 
experimental model, but no data are 
available on the usefulness of this drug in 
the clinical setting; anecdotal reports have 
been disappointing.
• Reduce ICP—osmotic diuretics: mannitol 
(1 g/kg slow IV infusion over 20 min, may 
repeat twice at 6-hour intervals) and/or loop 
diuretics: furosemide (dogs: 2–8 mg/kg IV/
IM/SC q12h; cats: 1–2 mg/kg IV/IM/SC 
q12h); these are short-term treatments only, 
helpful for acute treatment of severe cases.
• T reat underlying cause—administer specific 
drugs when possible (e.g., antibiotics for 
bacterial infection, irradiation, or surgery for 
• Corticosteroids—long-term treatment may 
cause iatrogenic hyperadrenocorticism or 
hypoadrenocorticism if drug is suddenly 
withdrawn.
• Diuretics—may cause shock or electrolyte 
imbalances, especially hypokalemia with 
furosemide administration.
  FOLLOW-UP
Monitor for exacerbation of the 
hydrocephalus and for signs attributable to an underlying cause (e.g., intracranial 
• Brain herniation and death.
• Infection and blockage when ventriculo-
peritoneal shunting is carried out; shunt 
revision and specific treatment for bacterial 
infection are then indicated.
• Good to poor—depend on cause and 
severity.
• Mild congenital form—good prognosis; 
may require only occasional medical 
Cerebellar hypoplasia in kittens congenitally 
infected with feline panleukopenia virus.
Congenital—usually seen in animals <1 year 
old.
SEE ALSO
• EEG = electroencephalography.
• ICP = intracranial pressure.
De Lahunta A, Glass E, Kent M. Veterinary 
pp. 91–101.
the brain. In: Dewey CW, ed., A Practical 
126–129, 193.
Kawasaki Y, Tsuruta T, Setogawa Y, 
Sakamoto H. Hydrocephalus with visual 
deficits in a cat. J Vet Med Sci 2006, 
65:1361–1364.
Thomas WB. Hydrocephalus in dogs and 
2010, 40:143–159.
Author  Stephanie Kube
available onlineHydrocephalus  (continued)

Canine and Feline, Seventh Edition  665
H  BASICS
OVERVIEW
• Hydronephrosis is progressive distention of 
the renal pelvis resulting in compression and 
atrophy of the renal parenchyma secondary to 
ureteral outflow tract obstruction and 
associated increased hydrostatic pressure.
• Most often hydronephrosis is unilateral 
(~80–85%) and occurs secondary to complete 
or partial obstruction of the ureter by 
uroliths, ureteral strictures, ureteral or 
trigonal neoplasia, retroperitoneal disease 
causing extraluminal compression, spay 
stump granuloma, trauma, radiotherapy, and 
accidental ligation of the ureter during 
ovariohysterectomy, cryptorchectomy, or after 
ectopic ureter surgery.
• Bilateral hydronephrosis is less common, 
resulting from ureteral stone disease, congenital 
ureteral strictures, trigonal neoplasia, or a 
urethral outflow obstruction. Severe hydro­
nephrosis can also be seen in dogs with ectopic 
ureters (commonly males) associated with a 
ureterovesical junction (UVJ) stenosis.
SIGNS
• Subclinical in some dogs/cats.
• Polyuria and/or polydipsia (PU/PD).
• Depression, diarrhea, vomiting associated 
with uremia in patients with bilateral 
hydronephrosis or with compromised 
function in the contralateral kidney.
• May be referable to the cause of the 
obstruction (e.g., abdominal pain).
• Most dogs and cats with a ureteral 
obstruction will continue to produce urine 
due to the unilateral nature of the condition 
or the presence of a partial, rather than 
complete, ureteral obstruction.
• Normal in some patients.
• Big kidney–little kidney syndrome 
associated with a previous ureteral obstruction.
• Renal, abdominal, or lumbar pain.
• Abdominal mass—bladder or prostate.
• T rigonal, prostatic, vaginal or urethral mass 
palpable on rectal exam.
Ureteral Diseases
• Ureteroliths.
• Congenital ureteral stricture or circumcaval 
ureter.• Acquired ureteral stricture/fibrosis.
• Pyonephrosis/pyoureter.
• Ureteral ligation during ovariohysterectomy.
• Secondary to congenital ectopic ureter.
• Complication from previous ectopic ureter 
surgery.
Lower Urogenital Tract Diseases
• Urinary bladder neoplasia (e.g., transitional 
cell carcinoma).
• Prostatic disease (e.g., neoplasia).
• Vaginal mass.
• Cryptorchectomy resulting in inadvertent 
prostatectomy.
Retroperitoneal Disease
• Masses—granuloma, neoplasm, cyst, 
abscess, hematoma.
• Post­radiotherapy ­induced fibrosis.
  DIAGNOSIS
• Other causes for renal pelvic dilation—e.g., 
ureteral obstruction (stone, stricture, tumor), 
pyelonephritis, pyelonephrosis, IV fluid 
therapy, chronic kidney disease, PU/PD.
• Other causes of renomegaly—e.g., 
neoplasia, cysts, and perinephric pseudocysts 
(cats).
• Other causes of abdominal pain—e.g., 
pancreatitis and peritonitis.
• Intervertebral disc disease leading to lumbar 
pain.
• Other causes for azotemia—e.g., acute 
kidney injury, chronic kidney disease, 
dehydration, urethral obstruction.
• Loss of urine ­concentrating ability 
(first abnormality detected), hematuria, 
pyuria.
• Azotemia, hyperphosphatemia, 
hyperkalemia, thrombocytopenia, and 
acidemia with either bilateral ureteral 
obstructions, concurrent renal parenchymal 
disease, or obstructive pyonephrosis.
IMAGING
• Abdominal radiographs may be normal or 
show nephroliths, ureteroliths, cystoliths, 
urethroliths, renomegaly, prostatomegaly, 
reduced retroperitoneal contrast, ureteral 
distension, or urinary bladder distension.
• Ultrasonography reveals dilation of the 
renal pelvis and diverticula, with thinning of 
the renal parenchyma; proximal dilation of 
affected ureter is detected in some dogs/cats 
if the hydronephrosis is associated with a 
ureteral obstruction (most common cause). 
If ureteral dilation is present, evaluation for cause (UVJ tumor, stenosis; ureteral stones; 
ureteral stricture).
• Injection of radiographic contrast 
material via either excretory urography (not 
recommended) or by nephropyelocentesis and 
ureteropyelography/retrograde ureterogram 
may be required to determine the location 
and cause of obstruction.
• CT can be helpful in cases where ultrasound 
and radiographs cannot determine cause.
Cystoscopy or vaginoscopy may help 
determine the location and cause of lower 
urinary tract obstruction or presence of 
ureteral ectopia, UVJ stenosis.
  TREATMENT
• Emergency intervention is required for 
ureteral obstruction; metabolic and electrolyte 
abnormalities should be corrected prior to 
intervention. If severe enough then hemo­
dialysis may be indicated.
• T reat as an inpatient.
• Start supportive care (e.g., fluids ± 
antibiotics) while performing diagnostic tests.
• Correct fluid and electrolyte deficits 
conservatively with IV fluid therapy over 
12–24 hours, followed by maintenance fluids 
as needed. Patients with extreme PU may need 
higher maintenance fluid rates to maintain 
hydration. Do not fluid overload patients.
• Pending reestablishment of urinary patency, 
relieve lower urinary tract obstruction by 
catheterization, serial cystocentesis, or tube 
cystostomy as soon as possible.
• Specific treatment (e.g., interventional or 
surgical) depends on the cause and whether 
there is concurrent kidney disease or other 
disease processes (e.g., bilateral uroliths 
affecting contralateral kidney and/or ureter, 
metastatic neoplasia, etc.).
• Nephrectomy is rarely ever indicated (e.g., 
• Success rate for medical management of 
obstruction is 8–13%.
• For a ureteral obstruction caused by 
uroliths—alpha ­adrenergic blockade should 
be considered (cat: prazosin 0.25 mg/cat 
q12h; dog: 1 mg/15 kg q8–12h).
• IV fluid diuresis—being careful to avoid 
overhydration.
• Diuretics, e.g., mannitol 0.25 g/kg bolus 
over 30 min; consider CRI (1 mg/kg/min) if 
effective.Hydronephrosis

666  Blackwell’s Five-Minute Veterinary Consult  
H• Hyperkalemia is often absent. Mild to 
moderate hyperkalemia often resolves with 
fluid replacement and/or bicarbonate 
administration unless bilateral obstruction 
and/or oliguria is present. Severe, symptomatic 
hyperkalemia requires prompt and aggressive 
medical or surgical management for emergent 
• Do not add or mix sodium bicarbonate 
with calcium ­containing fluids.
• Do not give radiographic contrast material 
intravenously until the patient is rehydrated. 
Use radiographic contrast material with 
caution in azotemic patients.
Special Considerations
A patient with ureteral obstruction(s) should 
be considered an emergency and referred to 
colleagues who are highly experienced in 
managing this condition.
  FOLLOW-UP
• Ultrasonography—can repeat at 2–4 ­week 
intervals after relief of obstruction to assess improvement. Often some signs of resolution 
appear within days after relief of obstruction, 
but can take up to 3–4 months.
• Monitor serum chemistries and electrolytes 
as needed. Symmetric dimethylarginine 
(SDMA) likely has a place in the months 
following obstruction to track chronic kidney 
disease development.
• After relief of obstruction— PU and 
postobstructive diuresis may lead to 
hypokalemia, weight loss, dehydration, and 
possibly permanent renal injury, so care 
should be taken to monitor these patients 
carefully.
Rupture of the excretory system and 
irreversible renal damage. Decompression 
should be considered when medical 
management fails to relieve obstruction.
• Variable depending on the cause, duration 
of obstruction, and presence or absence of 
concurrent infection.
• Irreversible damage to the kidney usually 
begins 15–45 days after obstruction.
• If the obstruction is relieved within  
2–4 weeks, some renal damage is reversible. 
If the obstruction is partial (over 80% of 
cases), the time before irreversible damage is 
prolonged.• Concurrent infection accelerates the 
severity of renal damage. Antimicrobial 
therapy is often initiated empirically, however 
recent research recommends performing 
ultrasound guided pyelocentesis followed by 
anterograde pyelographic contrast study to 
confirm or rule ­out ureteral obstruction.
SEE ALSO
• Acidosis, Metabolic.
• UVJ = ureterovesicular junction.
Acknowledgment  The authors and 
contributions of Allyson C. Berent and  
Cathy E. Langston.Hydronephrosis  (continued)

Canine and Feline, Seventh Edition  667
HHyperadrenocorticism (Cushing’s Syndrome)—Cats
  BASICS
OVERVIEW
Feline Cushing’s syndrome (FCS) or 
hyperadrenocorticism is a consequence of 
abnormally increased functional activity of 
the adrenal cortex.
Pathophysiology
• Caused by increased glucocorticoid 
secretion by the adrenal gland(s).
• Approximately 85% of cases due to bilateral 
adrenocortical hyperplasia from pituitary 
hyperplasia or tumor— pituitary-dependent 
hyperadrenocorticism (PDH).
• Remaining 15% caused by adrenal tumor 
(AT), half of which are benign.
• Regardless of etiology, concurrent 
unregulated diabetes mellitus (DM) is 
frequent (90%) and other concurrent diseases 
(e.g., pancreatitis, chronic kidney, or cardiac 
disease) are reported.
• Middle-aged to old cat.
• No known breed or sex predisposition.
SIGNS
• Dermatologic abnormalities (alopecia; 
unkempt hair coat; thin, fragile skin that is 
easily bruised or torn), polyuria, polydipsia, 
polyphagia, weight loss, muscle wasting, and 
pot-bellied appearance.
• Weight gain (unless concurrent DM causes 
weight loss), hepatomegaly, and curled pinnae 
also seen.
• Lethargy (dullness) secondary to muscle 
weakness or effects of pituitary mass.
• Excess sex hormones can cause signs such as 
penile barbs and behavioral changes (sexual).
• Pituitary adenoma with subsequent 
corticotropic hyperplasia and excess 
glucocorticoid secretion.
• Autonomously functioning benign adrenal 
adenoma (50%) or malignant adeno -
carcinoma (50%).
• Iatrogenic from glucocorticoid 
administration (rare).
  DIAGNOSIS
• Insulin-resistant DM.
• Hepatopathy.
• Sex hormone–secreting adrenal tumor.
• Hyperprogesteronism.
• Dermatologic disease.CBC/BIOCHEMISTRY/URINALYSIS
• Lymphopenia, anemia.
• Hyperglycemia, hypercholesterolemia, 
hypertriglyceridemia, hypochloremia.
• Elevated urine cortisol : creatinine 
(UC : Cr) ratio, proteinuria.
• Azotemia, hyperglobulinemia (less 
common).
• Elevated serum alkaline phosphatase 
uncommon.
• UC : Cr—sensitive (good negative 
predictive value).
• Low-dose dexamethasone-suppression 
test—good sensitivity. Dose: 0.1 mg/kg IV. 
Failure to suppress consistent with FCS.
• Adrenocorticotropic hormone (ACTH) 
stimulation test—specific but poorly 
sensitive, not recommended as initial 
diagnostic test.
• Assays for plasma sex hormone and 
progesterone concentrations may rule out 
differentials.
Differentiating Tests
• Plasma endogenous ACTH concentration 
high normal or greater with PDH compared 
to low plasma ACTH levels with AT ( <10 pg/
mL). Reference ranges vary with laboratories.
• Imaging.
IMAGING
• Abdominal ultrasound—accurate to 
differentiate PDH from AT in most cases; 
operator dependent. Symmetric adrenal 
glands of normal or enlarged size are 
suggestive of PDH; unilateral enlargement or 
asymmetric adrenal glands support AT.
• CT and MRI—visualization and 
measurement of pituitary tumors or 
characterization of adrenal tumors.
  TREATMENT
• FCS is a debilitating disease. Prognosis is 
guarded due to severity of complications and 
concurrent diseases.
• Presurgical medical treatment is beneficial 
to prevent complications from fragile skin 
and infections.
• Radiation therapy of macroadenomas 
allows better control of the disease and insulin 
• Unilateral adrenalectomy for AT and 
medical therapy for PDH are the most readily 
available effective treatment options.
• Hypophysectomy (microsurgical 
transsphenoidal) is effective and available at 
some institutions.  MEDICATIONS
• T rilostane reversibly blocks steroid 
synthesis. In most patients with FCS from 
PDH, trilostane reduces clinical signs and 
improves endocrine test results. A starting 
dose of 5–10 mg/cat PO q12h is 
• Mitotane (Lysodren®; o,p ′-DDD) is not 
recommended for treatment of FCS.
• Other medications have limited efficacy 
(ketoconazole, metyrapone, and amino- 
glutethimide).
FOLLOW-UP
• Clinical improvement and improved 
diabetic control are indicative of successful 
drug therapy.
• ACTH stimulation tests are recommended 
for dose adjustments of trilostane.
• AT = adrenal tumor.
• FCS = feline Cushing’s syndrome.
• PDH = pituitary-dependent 
• UC : Cr = urine cortisol : creatinine.
Feldman EC, Nelson RW. 
Hyperadrenocorticism in cats (Cushing’s 
syndrome). In: Feldman EC, Nelson RW, 
eds., Canine and Feline Endocrinology and 
Reproduction, 3rd ed. Philadelphia, PA: 
Saunders, 2004, pp. 358–393.
Mellet, K, Bruyette, D, Stanley, S. T rilostane 
therapy for treatment of spontaneous 
hyperadrenocorticism in cats: 15 cases 
(2004–2012). J Vet Intern Med 2013, 
27:1471–1477.
Valentin SY, Cortright CC, Nelson RH, et al. 
Clinical findings, diagnostic test results and 
treatment outcome in cats with spontaneous 
hyperadrenocorticism: 30 cases. J Vet Intern 
Med 2014, 28:481–487.
Author  Suzy Y.M. Valentin
of Deirdre Chiaramonte.

668  Blackwell’s Five-Minute Veterinary Consult  
HHyperadrenocorticism (Cushing’s Syndrome)—Dogs
  BASICS
• Spontaneous hyperadrenocorticism 
(HAC)—disorder due to excessive production 
of cortisol by adrenal cortex.
• Iatrogenic HAC—from excessive exogenous 
administration of glucocorticoids by any route.
• Clinical signs due to effects of elevated 
circulating glucocorticoid concentrations.
• ~80–85% of cases of naturally occurring 
HAC due to bilateral adrenocortical hyperplasia 
resulting from pituitary corticotroph adenoma 
or hyperplasia with oversecretion of adreno­
corticotropic hormone (ACTH).
• In remaining 15–20%, cortisol ­secreting 
adrenocortical neoplasia (AN) present; ~50% 
• Rarely caused by ectopic ACTH secretion 
from nonpituitary tumor.
• One case of food ­dependent hypercortisolemia 
reported, with increased cortisol concentration 
after meal; likely due to aberrant gastric 
inhibitory peptide receptors stimulating adrenal 
steroidogenesis.
• Iatrogenic HAC from excessive administration 
of exogenous glucocorticoids.
• Signs referable to urinary tract or skin 
common.
• Skin—bilaterally symmetric alopecia, 
comedones, hyperpigmentation, recurrent 
pyoderma.
PD; 85–90% of cases), proteinuria, urinary 
tract infections (UTIs).
• Endocrine/metabolic—hyperglycemia; 
diabetes mellitus (DM) in 10%.
• Cardiovascular—hypertension (usually mild).
• Gastrointestinal—polyphagia.
• Hemic/lymphatic/immune—stress 
leukogram, immunosuppression, mild 
erythrocytosis and thrombocytosis, occasional 
nucleated red blood cells.
• Hepatobiliary—hepatopathy due to glycogen 
deposition, increased serum alkaline phosphatase 
(ALP) activity due to corticosteroid ­induced 
isoenzyme; alanine aminotransferase (ALT) 
activity also increased, but by less.
• Neuromuscular—muscle weakness; CNS 
signs from macroadenoma may include 
anorexia, abnormal mentation, blindness, 
rarely seizures.
• Reproductive—testicular atrophy, anestrus.
• Respiratory—panting, pulmonary 
thromboembolism possible.
One of most common endocrine disorders 
in dogs.SIGNALMENT
Species
Dog
Poodle, dachshund, Boston terrier, German 
shepherd dog, beagle.
Generally, middle ­aged to older animals; 
pituitary ­dependent HAC (PDH) rarely seen 
in dogs as young as 1 year.
SIGNS
• Severity varies greatly, depending on 
duration and extent of cortisol excess.
• In some cases physical presence of 
neoplastic process (pituitary or adrenal) 
contributes to illness.
Historical and Physical Examination 
Findings
PU/PD, polyphagia, pendulous abdomen, 
increased panting, hepatomegaly, hair loss, 
cutaneous hyperpigmentation, thin skin, muscle 
weakness, obesity, lethargy, muscle atrophy, 
comedones, bruising, testicular atrophy, 
anestrus, calcinosis cutis, facial nerve palsy.
CAUSES
• PDH—adenoma most common; 
adenocarcinomas rare; anterior pituitary 
involved in ~80% of cases, intermediate lobe 
in remainder; exact incidence of pituitary 
macroadenomas (tumors >1 cm diameter) 
unknown, may be 10–25%.
• AN—adenoma or carcinoma (50%).
• Ectopic ACTH secretion and food ­ 
dependent hypercortisolism—rare.
• Iatrogenic—due to glucocorticoid 
• None known for spontaneous disease.
• Administration of exogenous glucocorticoids 
(risk for iatrogenic HAC).
  DIAGNOSIS
• Depends on clinical and laboratory 
• Hypothyroidism, sex hormone dermatoses, 
alopecia X, sex hormone–secreting tumors, 
acromegaly, DM, hepatopathies, renal disease, 
other causes of PU/PD.
• Cortisol can decrease concentration of total 
T4; important to check for HAC in dogs with 
weight gain or dermatologic disease that 
could be misdiagnosed as hypothyroidism.
• Hemogram may show eosinopenia, 
lymphopenia, leukocytosis, neutrophilia, 
erythrocytosis, thrombocytosis.• Serum chemistry may show elevated 
cholesterol concentration; ALP activity high 
in ~85–90% and elevations proportionately 
greater than for ALT.
• Mild hyperglycemia common but only ~10% 
of dogs with HAC have concurrent DM.
• Urinalysis may reveal low specific gravity, 
proteinuria, hematuria, pyuria, and/or 
bacteriuria.
• Endocrine testing required in dogs with history, 
clinical signs, and laboratory abnormalities 
suggestive of HAC; see Appendix II.
• Do not perform HAC testing in sick dogs 
unless clinical signs consistent with HAC.
• Screening tests  determine if HAC present or 
not.
• Once diagnosis of HAC made, perform 
differentiation test  to determine if PDH or AN 
present; differentiation crucial for therapeutic 
decisions and prognosis.
• To convert cortisol concentration in 
nmol/L to μg/dL, divide by 27.6.
• All cortisol concentrations below for 
illustration; normal ranges and cut ­off values 
vary with lab.
Urine Cortisol : Creatinine Ratio 
(UC : Cr)
• Urine cortisol excretion increases with 
augmented adrenal secretion of cortisol, 
whether due to PDH or AN.
• Should be measured in urine sample 
collected at home when pet not stressed.
• Elevated UC : Cr is sensitive marker of 
HAC, present in 90–100% of affected dogs; 
normal ratio makes diagnosis of HAC very 
unlikely.
• False­positive results common; only ~20% 
of dogs with elevated UC : Cr have HAC.
• Due to chance of false ­positive, always do 
ACTH stimulation test or low ­dose 
dexamethasone suppression test to confirm 
presence of HAC.
Low-Dose Dexamethasone Suppression  
T est (LDDST)
• Lack of suppression 8h after injection of 
low dose of dexamethasone consistent with 
diagnosis of HAC.
• Sensitivity ~95% in dogs.
• In dogs with nonadrenal illness, relatively 
high chance of false ­positive.
• Lack of suppression at 4h but full 
suppression at 8h technically not consistent 
with HAC, but suspicious for its presence; 
further testing warranted.
• LDDST may also serve as differentiation 
test; if 8h sample >1.4 μg/dL, result 
consistent with HAC; if also suppression to 
<1.4 μg/dL at 4h post dexamethasone (i.e., 
“escape” at 8h post dexamethasone) or 4h 
and/or 8h post ­dexamethasone samples 
<50% of baseline, results consistent with

Canine and Feline, Seventh Edition  669
HPDH; if criteria for PDH not met, chances 
still ~⅔ for PDH vs. AN.
• If baseline values close to 1.4  μg/dL or 
suppression just at 50%, confirm presence of 
PDH by other means.
• Protocol exists in Utrecht, Netherlands, 
where min 2 morning urine samples collected 
and then dexamethasone administered (3 
doses over 24h) for differentiating purposes 
and another urine sample collected; protocol 
reportedly has high sensitivity and specificity, 
but urinary cortisol assay proprietary and not 
commercially available; accuracy of protocol 
using cortisol assays commercially available in 
United States not established, so method not 
recommended in North America.
ACTH Stimulation T est
• Response > normal consistent with 
diagnosis of spontaneous HAC, but cannot 
differentiate between PDH and AN.
• Overall sensitivity of test ~80%; for PDH, 
sensitivity ~87%; for HAC due to AN 
sensitivity ~61%.
• More specific in dogs than LDDST (only 
15% chance of false ­positive with nonadrenal 
illness).
• Only test that can diagnose iatrogenic 
HAC; diagnosis made with history of 
glucocorticoid exposure by any route, 
consistent clinical signs, and post ­ACTH 
cortisol concentration < reference range.
• Cosyntropin (or tetracosactrin) 
recommended form; if using compounded 
ACTH, collect samples before and at 1h and 
2h post ACTH administration so peak 
response not missed.
High-Dose Dexamethasone Suppression T est 
(HDDST)
• T wo responses consistent with PDH—  
suppression to <1.4 μg/dL at 4h and/or 8h post 
dexamethasone; or 4h and/or 8h post ­
dexamethasone samples <50% of baseline.
• Can never  confirm presence of AN; if 
criteria for diagnosis of PDH not met, 50/50 
chance patient has PDH or AN; since 
HDDST does not significantly increase 
ability to differentiate PDH from AN, 
endogenous ACTH (eACTH) and/or 
abdominal US used instead.
eACTH Concentration
• Requires only single blood sample, but 
inappropriate handling can lead to 
decreased eACTH concentrations due to 
degradation.
• In patients with PDH, eACTH 
 concentration usually normal to increased; 
with AN, eACTH concentration < normal.
• If concentration increased, consistent with 
PDH, but due to episodic secretion of ACTH even in patients with PDH, low value does 
not always confirm AN.
• If eACTH concentration falls in gray zone, 
results not diagnostic.
IMAGING
• Abdominal radiographs—~40–50% of 
canine ANs seen; adrenal mineralization 
suspicious for AN.
• Thoracic radiographs indicated in patients 
with AN to check for metastases.
• US—useful for staging AN, but poor 
screening test (adrenal enlargement occurs 
with chronic nonadrenal illness, AN may be 
difficult to see with US); adrenal atrophy can 
be difficult to determine with US, but 
bilaterally enlarged adrenal glands consistent 
with PDH; vena caval invasion and metastasis 
may be present with AN.
• CT and MRI—can show pituitary macro­
adenomas and assess AN invasion into 
adjacent structures; follow ­up and treatment 
recommendations (e.g., radiation therapy) 
may vary with tumor size.
Adrenal histopathology following  adrenalectomy 
for AN often needed to differentiate benign vs. 
malignant tumor; biopsy prior to removal may 
result in complications.
• PDH—normal to enlarged pituitary and 
bilateral adrenocortical enlargement.
• Microscopically, pituitary adenoma, adeno­
carcinoma, or corticotroph hyperplasia of pars 
distalis or pars intermedia and adrenocortical 
hyperplasia.
• AN—variable ­sized adrenal mass, atrophy 
of contralateral gland (rarely bilateral 
tumors), metastasis and invasion into vena 
cava with thrombosis possible.
• Microscopically, adrenocortical adenoma or 
  TREATMENT
Dictated by severity of clinical signs, patient’s 
overall condition, any complicating factors 
(e.g., DM, pulmonary thromboembolism).
• For medical therapy, lifelong therapy 
required.
• If adverse reaction to mitotane or trilostane 
occurs—discontinue drug, give dexamethisone,  
have veterinarian reevaluate next day; if no 
response noted in few hours, veterinarian 
should evaluate immediately.
• Hypophysectomy—described, but limited 
availability.
• Bilateral adrenalectomy not used for 
treatment of PDH.• Surgery treatment of choice in dogs with 
adrenocortical adenomas and carcinomas 
unless patient poor surgical candidate.
• Appropriate personnel and facilities 
required as adrenalectomy (especially with 
vena caval thrombi) is technically demanding 
and intensive postoperative management 
required.
• Surgery not curative, but long ­term survival 
possible
• Medical control of HAC may be desirable 
prior to surgery.
Trilostane
• T rilostane (Vetoryl®) inhibits adrenocortical 
enzyme 3 ­β­hydroxysteroid dehydrogenase 
and maybe others, thereby suppressing 
production of progesterone and its end ­
products, including cortisol and aldosterone 
(less than cortisol); efficacy and survival time 
for treatment of PDH excellent.
• Initial dose 2–3 mg/kg PO q24h (in morning) 
or divided q12h with food; twice ­daily dosing 
more expensive, but quicker resolution of clinical 
signs, fewer dose changes and monitoring tests; if 
q24h dosing elected and patient controlled 
during day but has more clinical signs at night, 
splitting daily dose ½ morning and ½ evening 
may improve clinical signs.
• Side effects include lethargy, decreased 
appetite, vomiting, diarrhea; sometimes occur 
within first few days of therapy and associated 
with gastrointestinal upset due to administra­
tion of oral medication; hypocortisolemia can 
also occur due to oversuppression of cortisol 
production and cause same clinical signs; 
rarely, idiosyncratic adrenal necrosis with 
hypocortisolemia and hypoaldosteronism, but 
less common with lower doses (as recom­
mended above).
• Monitoring—primary goals to control 
clinical signs and avoid complications 
(especially hypocortisolemia); should include 
assessment of clinical signs (PU/PD, 
polyphagia, panting) and cortisol testing (see 
below) to ensure cortisol not suppressed 
excessively; obtaining detailed history and 
evidence of potential oversuppression of 
cortisol imperative.
• Historically, ACTH stimulation test used to 
monitor trilostane therapy, 4–6h post trilostane 
administration; 1  μg/kg cosyntropin IV 
effective for monitoring, but not for diagnosis 
(must use 5  μg/kg); ideal post ­ACTH cortisol 
concentration 2–6  μg/dL, but must consider 
clinical signs; e.g., if patient clinically 
controlled with post ­ACTH cortisol of 7.2  μg/
dL, no need to increase dose; if clinical signs 
persist, dose increase recommended.(continued)  Hyperadrenocorticism (Cushing’s Syndrome)—Dogs

670  Blackwell’s Five-Minute Veterinary Consult  
H• Studies show post ­ACTH stimulation 
cortisol values do not always correlate well with 
clinical signs, measuring cortisol concentration 
before morning dose of trilostane may correlate 
better; assessing clinical signs imperative when 
using pre ­pill cortisol concentration for 
monitoring; if patient showing signs of 
hypocortisolemia (vomiting, diarrhea, decreased 
appetite), must use ACTH stimulation test; 
data lacking on decision ­making using pre ­pill 
cortisol, but some guidelines: cortisol 
concentration used to confirm patient not 
cortisol deficient (<1.4 ­2 μg/dL), clinical signs 
used to determine whether dose adequate; if 
patient clinically controlled and cortisol 
2–6  μg/dL, appropriate to continue current 
dose; if <2  μg/dL, perform ACTH stimulation 
test or decrease dose; if patient still clinical (PU/
PD, polyphagic, panting) and pre ­pill cortisol 
>6 μg/dL, safe to increase dose; in clinically 
uncontrolled patient, cortisol concentration 
2–6  μg/dL is gray zone: probably safe to 
increase dose if pre ­pill cortisol 5  μg/dL, but 
probably not at 2.5  μg/dL; perform ACTH 
stimulation test in this situation.
• Perform either ACTH stimulation test or 
pre­pill cortisol at 10–14 days, 30 days, and 
90 days after each dose change; if at 10–14 ­
day recheck any improvement seen, do not 
increase dose even if cortisol concentration 
above ideal; wait until 30 ­day recheck and 
change dose then if necessary, as effect of 
trilostane often increases between 2 and 4 
weeks; assess renal profile, including 
electrolytes, at 14 ­ or 30 ­day exam; once 
clinical condition and dose stabilized, perform 
pre­pill cortisol or ACTH stimulation test, 
and electrolyte panel, q3–6 months.
• If lethargy, decreased appetite, vomiting, or 
diarrhea occurs, ACTH stimulation test to 
confirm dog not hypocortisolemic (post ­ACTH 
stimulation cortisol <2  μg/dL); if hypocorti ­
solemia confirmed, assess electrolyte panel to 
ensure hyponatremia and hyperkalemia not 
present; discontinue trilostane until clinical signs 
of HAC recur and baseline and/or post ­ACTH 
cortisol concentrations >5 ­6 μg/dL.
• If signs of hypocortisolemia more severe 
than mild lethargy, vomiting, decreased 
appetite, give dexamethasone 0.1 mg/kg/day 
PO/IV, then taper to lowest effective dose to 
control signs; if signs of HAC recur, taper 
dexamethasone and discontinue, then 
perform baseline cortisol and/or ACTH 
stimulation test interpreted as above; if 
dexamethasone unavailable and prednisone 
used instead, delay cortisol testing until at 
least 24h after last prednisone dose, as 
prednisone can cross ­react with cortisol assay.
• If more severe signs occur, hospitalization 
with IV fluids, dexamethasone, and other 
supportive therapy necessary.
• Hypocortisolemia secondary to trilostane 
administration usually resolves within 48–72h of drug discontinuation, but temporary 
cortisol suppression of weeks to months and 
even permanent suppression can occur.
• T rilostane can be used to treat hypercorti­
solemia from AN and usually controls clinical 
signs; although mitotane theoretically 
preferred due to chemotherapeutic properties, 
no difference shown between survival of 
patients with AN treated with mitotane or 
trilostane.
Mitotane
• Mitotane (o,p ′­DDD, Lysodren®) 
selectively destroys glucocorticoid ­secreting 
cells of adrenal cortex; in patients with AN 
may destroy tumor cells as well as controlling 
cortisol secretion, but no difference in 
survival between dogs with AN receiving 
mitotane vs. trilostane.
• PDH—initial loading dose 40–50 mg/kg 
PO divided twice daily; evaluate efficacy with 
ACTH stimulation test after 8 days, or sooner 
if decreased appetite, vomiting, diarrhea, 
listlessness, decreased water intake ( <60 mL/
kg/day); target for both basal and post ­ACTH 
cortisol concentration 1–5  μg/dL; continue 
induction with repeat testing as necessary 
until adequate response, then initiate 
maintenance therapy at 50 mg/kg/week PO 
divided in 2–3 doses; adjust dosage based on 
ACTH stimulation testing (to maintain basal 
and post ­ACTH cortisol levels in ideal range); 
if serum cortisol concentration pre ­ or 
post­ACTH <1 μg/dL, measure electrolyte 
concentrations, stop administering mitotane, 
and give physiologic doses of prednisone 
(0.1 mg/kg PO q12h; do not give within 24h 
before ACTH stimulation test); cortisol 
secretion usually recovers in weeks to months 
but can take longer; once cortisol concen­
tration in ideal range, discontinue prednisone 
and begin maintenance therapy; if dog was on 
maintenance therapy when became cortisol 
deficient, restart maintenance at 25% lower 
dose; if relapse occurs at any time on 
maintenance therapy (as indicated by cortisol 
levels above ideal range), dose adjustment 
required; if post ­ACTH serum cortisol 
concentration 5–10  μg/dL, increase mainte ­
nance mitotane dose by 25% and reevaluate in 
4 weeks; if post ­ACTH serum cortisol 
concentration >10 μg/dL, repeat loading 
sequence for 5–7 days and repeat ACTH 
stimulation test; continue loading until 
cortisol concentration in ideal range, then 
reinitiate weekly maintenance dose at ~50% 
higher dose.
• AN—goal of mitotane to achieve low to 
nondetectable ( <1 μg/dL) basal and post ­
ACTH cortisol concentrations; starting dose 
50–75 mg/kg PO divided daily; perform 
ACTH stimulation test after 10–14 days of 
therapy to evaluate efficacy, sooner if 
decreased appetite, vomiting, diarrhea, lethargy, decreased water intake ( <60 mL/kg/
day); induction typically requires higher doses 
and longer duration than for treatment of 
PDH and dose should be increased by 50 mg/
kg/day q10–14 days if control not achieved 
(based on ACTH stimulation test); if adverse 
effects develop, continue administration at 
highest tolerable dose; once control achieved, 
begin maintenance therapy at 75–100 mg/kg/
week PO divided into 2–3 doses; if cortisol 
levels pre ­ and post ­ACTH rise into normal 
resting range (1–5  μg/dL), increase mainten­
ance dose by 50%; if cortisol levels rise above 
normal resting range pre ­ and post ­ACTH, 
reload until control achieved and increase 
weekly maintenance dose ~50%; because 
goal of induction and maintenance is to 
create glucocorticoid insufficiency, 
 prednisone should be administered at 
0.2 mg/kg/day PO.
• Aldosterone deficiency possible from 
mitotane therapy; if it occurs, patient  
will likely have permanent complete 
adrenocortical insufficiency and treatment  
for hypoadrenocorticism should be  
initiated.
l-Deprenyl
• l­Deprenyl (selegiline hydrochloride); FDA 
approved for treatment of PDH; decreases 
pituitary ACTH secretion, thus decreasing 
serum cortisol concentration.
• Questionable efficacy; not currently 
Ketoconazole (10 mg/kg PO q12h initially; 
up to 20 mg/kg PO q12h in some dogs) 
inhibits cortisol synthesis; no longer 
recommended (trilostane causes fewer side 
effects).
• Do not use ketoconazole with trilostane 
therapy (increased potential for hypocortisolism)
• Monitor for hyperkalemia if concurrent 
angiotensin ­converting enzyme inhibitor 
therapy.
• Side effects of trilostane include anorexia, 
lethargy, vomiting, diarrhea; usually mild and 
resolve with discontinuation and dose

effects).
therapy.
resolve with discontinuation and dose 
adjustment; Addisonian crisis and adreno­
cortical necrosis reported.
• Use trilostane and mitotane with caution in 
patients with renal insufficiency and hepatic 
disease; trilostane contraindicated in 
• Side effects of mitotane mild in most 
dogs; include lethargy, anorexia, vomiting, 
diarrhea, ataxia, iatrogenic hypoadrenocorticism.
• Side effects more common in dogs with AN 
given high dose mitotane.
• In diabetic patients, insulin requirement 
can decrease with control of HAC.Hyperadrenocorticism (Cushing’s Syndrome)—Dogs  (continued)

Canine and Feline, Seventh Edition  671
HALTERNATIVE DRUG(S)
Radiation therapy possible to treat pituitary 
macroadenomas. T reatment with trilostane or 
mitotane still usually required afterwards. 
ACTH levels may take several months to 
decrease and HAC controlled with drugs in 
interim.
  FOLLOW-UP
• Response to therapy—use periodic ACTH 
stimulation and/or cortisol testing to assess 
trilostane and mitotane efficacy (see above); 
once on maintenance mitotane therapy, test 
at 1, 3, and 6 months and q3–6 months 
thereafter or if clinical signs of HAC recur.
• Adequacy of any mitotane reloading period 
checked with ACTH stimulation test before 
higher maintenance dose initiated.
• Adequacy of trilostane dose alterations 
checked with ACTH stimulation test 
performed 4–6h after dosing.
For prevention of recurrence and hypocorti ­
solemia, regular administration of medications 
with appropriate follow ­up required.
• Recurrent infections.
• Urinary calculi (calcium oxalate).
• DM.
• Pulmonary thromboembolism.
• Neurologic signs secondary to pituitary 
macroadenoma.
• Hypoadrenocorticism secondary to 
• Untreated HAC—progressive disorder with 
survival of 6–18 months.• T reated PDH—usually good prognosis; 
median survival time with mitotane or 
trilostane treatment ~2 years; at least 10% 
survive 4 years; dogs living >6 months tend to 
die of causes unrelated to HAC.
• Macroadenomas in animals with no or 
mild neurologic abnormalities have fair to 
good prognosis with radiation and medical 
therapy; in patients with significant 
neurologic abnormalities, prognosis poor to 
grave.
• Adrenal adenomas—usually good to 
excellent prognosis; small carcinomas (not 
metastasized) fair to good prognosis overall, 
good to excellent with surgical resection.
• Large carcinomas and AN with widespread 
metastasis—generally poor to fair prognosis, 
but impressive responses to high doses of 
mitotane occasionally seen.
Neurologic signs in dogs with pituitary 
tumors; glucose intolerance or concurrent 
DM; pulmonary thromboembolism; 
increased incidence of infections, especially 
UTI and skin; hypertension; proteinuria/
glomerulopathy.
• AN = adrenal neoplasia.
• eACTH = endogenous ACTH.
• HAC = hyperadrenocorticism.
• HDDST = high ­dose dexamethasone ­
• LDDST = low ­dose dexamethasone ­ 
• PDH = pituitary ­dependent HAC.• PU/PD = polyuria/polydipsia.
Intern Med 2013, 27:1292–1304.
Braddock JA, Church DB, Robertson ID, 
et al. T rilostane treatment in dogs with 
pituitary ­dependent hyperadrenocorticism. 
Aust Vet J 2003, 81:600–607.
Kintzer PP , Peterson ME. Mitotane (o,p ′­
ddd) treatment of 200 dogs with pituitary ­
dependent hyperadenocorticism. J Vet 
Intern Med 1991, 5:182–190.
Nagata N, Kokima K, Yuki M. Comparison 
of survival times for dogs with pituitary ­
dependent hyperadrenocorticism in a 
primary ­care hospital: treated with 
trilostane versus untreated. J Vet Intern 
Med 2017, 31:22–28.
Vaughn MA, Feldman EC, Hoar BR, Nelson 
RW. Evaluation of twice ­daily, low ­dose 
trilostane treatment administered orally  
in dogs with naturally occurring  
hyperadrenocorticism. J Am Vet Med Assoc 
2008, 232:1321–1328.
Author  Patty A. Lathan
Deborah S. Greco
available online(continued)  Hyperadrenocorticism (Cushing’s Syndrome)—Dogs

672  Blackwell’s Five-Minute Veterinary Consult  
HHypercalcemia
  BASICS
• Serum total calcium >11.5 mg/dL (dogs).
• Serum total calcium >10.5 mg/dL (cats).
• Serum ionized calcium >1.45 mmol/L 
(dogs).
• Serum ionized calcium >1.4 mmol/L (cats).
• Hypercalcemia must be confirmed by 
demonstration of increased concentrations of 
ionized  calcium.
• Total calcium concentrations and correction 
formulas do not accurately predict ionized 
calcium and their use is discouraged.
• Control of calcium is complex, tightly 
regulated, and influenced by the actions of 
parathyroid hormone (PTH), vitamin D, and 
the interaction of these hormones with the 
gastrointestinal tract, bone, kidneys, and 
parathyroid glands.
• Derangement in the function of these can 
lead to hypercalcemia.
• Secretory products of some neoplastic cells 
can also disturb calcium homeostasis.
• Cardiovascular—hypertension and altered 
cardiac contractility.
• Gastrointestinal—reduced smooth muscle 
excitability and potentially altered gastro­
intestinal function.
• Neuromuscular—depressed skeletal muscle 
contractility causes weakness.
• Renal/urologic—high calcium concentrations 
are toxic to the renal tubules and can cause 
polyuria and polydipsia (PU/PD) and renal 
failure; can also lead to urolithiasis and 
associated lower urinary tract disease.
• Primary hyperparathyroidism in the 
keeshond and Siamese cats.
• Primary hyperparathyroidism and neoplasia 
are more likely in geriatric dogs.
SIGNS
• Depend on the cause of hypercalcemia.
• Patients with underlying neoplasia, renal 
failure, or hypoadrenocorticism generally 
appear ill.
• Patients with primary hyperparathyroidism 
show mild clinical signs, if any.
• Signs become apparent when hypercalcemia 
is severe and chronic.
• Many asymptomatic.
• PU/PD—most common in dogs.
• Lethargy—most common in cats.
• Constipation.• Weakness.
• Stupor and coma—severe cases.
• Lower urinary tract signs (e.g., stranguria) 
in animals with secondary calcium ­containing 
uroliths.
• Lymphadenomegaly or abdominal 
organomegaly (patients with lymphoma).
• Rectal or mammary masses.
• Fundic examination may reveal evidence for 
granulomatous disease.
• Unremarkable in dogs with primary 
hyperparathyroidism.
• Parathyroid gland adenoma may be 
palpable in cats with primary 
hyperparathyroidism, but can be confused 
with the thyroid gland.
CAUSES
• Neoplasia—lymphoma (most common in 
dogs, less common in cats), anal sac apocrine 
gland adenocarcinoma (dogs), multiple 
myeloma, lymphocytic leukemia, metastatic 
bone tumor, fibrosarcoma (cats), other 
• Primary hyperparathyroidism.
• Renal failure (acute or chronic).
• Granulomatous diseases (blastomycosis, 
histoplasmosis, schistosomiasis).
• Vitamin D intoxication from ingestion of 
human psoriasis medication or cholecalciferol 
rodenticide, or from plant or food sources.
• Osteolytic diseases.
• Idiopathic (most common cause in cats).
• Laboratory error.
• Occasionally observed in cats with 
• Keeshond breed (hyperparathyroidism).
• Use of calcium supplements or calcium ­
containing intestinal phosphate binders.
• Use of calcitriol or other vitamin D 
preparations.
  DIAGNOSIS
• History should include questions 
regarding exposure to exogenous vitamin D 
sources and any previous response to 
• History of waxing/waning illness suggests 
hypoadrenocorticism, renal failure, or 
emerging neoplasia.
• Complete lymph node, rectal, and 
abdominal palpation may raise index of 
suspicion for lymphoma or other neoplasia.
• Assessment of hydration status, renal 
palpation, and urinary history may point 
toward renal or lower urinary tract disease.LABORATORY FINDINGS
• Oxalate, citrate, and EDTA anticoagulants 
bind calcium and falsely lower calcium 
measurement.
• Thiazide diuretics can raise serum calcium 
Results
• Hemolysis and lipemia can falsely raise 
calcium concentrations.
• Hypoalbuminemia can lower total calcium 
Yes
• Serum calcium—total calcium concentrations 
reflect the combination of protein ­bound 
calcium, complexed calcium, and biologically 
active ionized calcium; elevations in total 
calcium should prompt clinicians to evaluate 
ionized calcium concentrations.
• Azotemia and urine specific gravity help to 
define degree of renal impairment.
• Serum phosphorus is usually low or 
low­normal in patients with primary 
hyperparathyroidism or hypercalcemia 
associated with malignancy.
• Hyperphosphatemia in the absence of 
azotemia suggests a nonparathyroid cause 
of hypercalcemia.
• Combination of hyperphosphatemia and 
azotemia is difficult to interpret because 
renal failure can be the cause or effect of 
• Hyperkalemia and hyponatremia suggest 
• Hyperglobulinemia is associated with 
multiple myeloma.
• Cytopenias are seen in patients with 
myelophthisic disease.
• Serum ionized calcium is high in patients 
with primary hyperparathyroidism or 
hypercalcemia associated with malignancy; 
usually normal or low in patients with 
hypercalcemia associated with renal  
failure.
• Serum PTH measurement—intact 
molecule and two ­site assay methods have the 
greatest specificity; high ­normal or high 
concentration suggests primary hyperpara­
thyroidism; can be high in patients with 
chronic renal failure; low concentration 
makes neoplasia more likely; normal PTH 
concentrations do not exclude a diagnosis of 
primary hyperparathyroidism.
• Serum PTH ­related peptide (PTH ­rp) 
measurement is often high in patients with 
lack of elevation in PTH ­rp concentration 
does not exclude neoplasia as a possible cause 
of hypercalcemia.

Canine and Feline, Seventh Edition  673
H• Serum Vitamin D assays are available at 
specific laboratories.
• Fecal PCR testing for schistosomiasis.
IMAGING
• Radiography is useful for assessing renal size 
and shape, urolithiasis, bone lysis, pulmonary 
infiltration, lymphadenomegaly, and occult 
• Ultrasonography is valuable for assessing 
renal architecture, abdominal lymphadeno­
megaly, parathyroid tumors, and urolithiasis.
• Cytologic examination of fine ­needle 
aspirate of lymph nodes, liver, spleen, anal 
glands, or other tumors or masses to diagnose 
• Bone marrow aspirate or biopsy—to 
identify occult hematopoietic neoplasia.
stimulation testing to confirm 
  TREATMENT
• Definitive treatment of hypercalcemia is 
achieved by identification and correction of 
the primary cause.
• Inpatient care may be necessary because of 
the deleterious effects of hypercalcemia and 
the need for fluid therapy (diuresis).
• Consider severe hypercalcemia (ionized 
calcium >2.2 mmol/L) a medical emergency.
• Normal saline—fluid of choice (sodium 
promotes calcium excretion).
• Diuretics (furosemide) and corticosteroids 
promote calciuresis.
• Pamidronate or other bisphosphonate drugs 
(e.g., alendronate) have been used successfully 
for treatment of hypercalcemia of various 
causes in dogs and cats.
• Do not use glucocorticoids until the 
diagnosis of lymphoma or other round cell 
neoplasia is excluded; they can obfuscate the 
diagnosis; if hypoadrenocorticism is 
suspected, do not give glucocorticoids until 
after ACTH stimulation testing, or use dexamethasone, which will not interfere with 
the serum cortisol assay.
• Thiazide diuretics can cause calcium 
retention.
• Oral bisphosphonates can cause esophageal 
erosions and should be used with caution.
Do not give diuretics to a dehydrated  
patient.
Avoid the use of calcium or phosphorus ­
containing compounds; they can cause soft 
tissue mineralization in severely hypercalce­
mic and hyperphosphatemic patients.
• Sodium bicarbonate (1–4 mEq/kg) may be 
useful in combination with other treatments 
when metabolic acidosis is present.
• Calcitonin may be useful in the treatment 
of hypervitaminosis D.
• Hemodialysis and peritoneal dialysis are 
alternative treatments for some causes of hyper  ­ 
calcemia, but cost and availability limit their use.
• Novel therapies like calcimimetic drugs 
may hold potential for certain causes of 
hypercalcemia such as idiopathic hypercalce­
mia or primary hyperparathyroidism; cost is 
currently a deterrent, as is lack of routine 
efficacy.
• Mithramycin has been used in severe 
hypercalcemic crises; avoid its use because 
of associated nephrotoxicity and hepato  ­ 
toxicity.
  FOLLOW-UP
• Serum calcium every 12 hours (ionized 
calcium if possible).
• Renal function assessment—the first sign of 
tubular damage may be casts in the urine 
sediment.
• Must closely monitor urine output, 
particularly if oligo ­anuric renal failure is 
present.
• Hydration status must be monitored; 
indicators of overhydration include increased 
bodyweight, chemosis, and edema 
(pulmonary or subcutaneous).
• Irreversible renal failure.
• Soft tissue mineralization.  MISCELLANEOUS
Calcium ­containing urolithiasis.
• Mild elevations in calcium and phosphorus 
may be normal in growing animals.
• Middle ­aged and older dogs and cats are at 
increased risk for cancer.
A fetus is at the same risk as the dam; do not 
alter treatment because of pregnancy.
SEE ALSO
• Hyperparathyroidism.
• Lymphoma—Dogs.
• Paraneoplastic Syndromes.
• PTH = parathyroid hormone.
• PTH ­rp = parathyroid hormone–related 
peptide.
Daniels E, Sakakeeny C. Hypercalcemia: 
pathophysiology, clinical signs, and 
emergent treatment. J Am Anim Hosp 
Assoc 2015, 51(5):291–299.
de Brito Galvao JF , Parker V, Schenck PA, 
Chew DJ. Update on feline ionized 
hypercalcemia. Vet Clin North Am Small 
Anim Pract 2017, 47(2):273–292.
Greco DS. Endocrine causes of calcium 
disorders. Top Companion Anim Med 
2012, 27(4):150–155.
Hostutler RA, Chew DJ, Jaeger JQ, et al. Uses 
and effectiveness of pamidronate disodium for 
treatment of dogs and cats with hypercalcemia. 
J Vet Intern Med 2005, 19(1):29–33.
Schenck PA, Chew DJ. Calcium: total or 
ionized? Vet Clin North Am Small Anim 
Pract 2008, 38(3):497–502.
Author  Brett A. Wasik
Thomas K. Graves
available online(continued)  Hypercalcemia

674  Blackwell’s Five-Minute Veterinary Consult  
HHypercapnia
  BASICS
• An increase in the partial pressure of carbon 
dioxide in arterial blood (PaCO2).
• Normal PaCO2 values—35–45 mmHg.
• Hypercapnia is synonymous with 
hypercarbia.
• CO2—end product of aerobic cellular 
metabolism; considered the primary drive for 
ventilation by stimulation of central chemo­
receptors in the medulla oblongata; carried in 
the blood in three forms: bicarbonate (65%), 
bound to hemoglobin (30%), and dissolved in 
plasma (5%; the source of PaCO2 values); 
constantly being added to alveolar gas from the 
pulmonary circulation and removed by alveolar 
• Uncommonly encountered in nonanesthe­
tized, clinically normal patient; result of 
alveolar hypoventilation.
• Cardiovascular—may result in endogenous 
catecholamine release, which may induce 
cardiac arrhythmias; may cause vasodilation 
leading to hypotension.
• Hemic/lymphatic/immune—may alter 
acid­base balance; acute increase results in 
production of excess hydrogen ions and 
decrease in pH (respiratory acidosis).
• Nervous—brain is primary affected organ; 
cerebral blood flow related to PaCO2 in a 
linear fashion; hypercapnia results in 
increased cerebral blood flow and intracranial 
pressure; PaCO2 >90 mmHg may lead to 
CO2 narcosis and unconsciousness.
Any breed, age, and sex of dog and cat.
SIGNS
• Abnormal breathing pattern.
• Weakness—secondary to concurrent 
hypoxemia or primary neuromuscular disease.
• Anesthetized patients—usually no obvious 
signs; severe condition may lead to tachypnea, 
hypotension, and tachycardia.
• Hypoventilation owing to muscle weakness 
or neuropathy—weak respiratory efforts; 
decreased thoracic excursion; excessive 
abdominal effort; exaggerated movement of 
facial muscles during inspiration; possibly 
generalized weakness as a result of primary 
neuromuscular disorder (myasthenia gravis, 
polyradiculoneuropathy).
• Upper airway obstruction—marked, 
prolonged inspiratory efforts with variable 
expirations, depending on whether the 
obstruction is fixed (e.g., mass) or nonfixed (e.g., 
laryngeal paralysis); stertor or stridor common.• Pleural effusion—may have shallow rapid 
respirations; may note a marked abdominal 
component; lung sounds decreased in ventral 
thorax.
• Pulmonary parenchymal disease—increased 
bronchovesicular sounds; crackles (edema, 
infection, contusions).
CAUSES
• Hypoventilation can result from anesthesia, 
muscular paralysis, upper airway obstruction, 
air or fluid in the pleural space, restriction in 
movement of the thoracic cage, diaphrag­
matic hernia, pulmonary parenchymal 
disease, drug therapy to control seizures, 
opioid and alpha ­2 agonist use for analgesia, 
and CNS disease. Can occur in spontaneously 
breathing patients during inhalation 
anesthesia (isoflurane or sevoflurane).
• Increased inspired CO2—rebreathing of 
expired gases because of accumulation of 
exhausted CO2 absorbent in an anesthesia 
machine most common cause; also 
inadequate fresh gas flow in a non ­
rebreathing anesthesia circuit (e.g., Bain  
and Ayres T ­Piece).
• Exogenous administration of sodium 
bicarbonate, which dissociates into CO2, with 
inadequate ventilation.
• Use of inhalation agent (isoflurane or 
sevoflurane) as sole anesthetic, since 
inhalation anesthetics are potent respiratory 
depressants.
• Use of opioid or alpha ­2 agonist analgesia.
• Deep planes of inhalation anesthesia.
• Inadequate fresh flow of oxygen with 
non­rebreathing anesthesia circuits.
• Bronchial or alveolar disease.
• Upper airway obstruction.
• Pleural disease.
• Inadequate ventilation during 
administration of sodium bicarbonate.
• Severe cervical spinal cord compression.
• Severe lower motor neuron disease.
  DIAGNOSIS
• Conscious patient—hyperthermia; 
hypoxemia; head trauma.
• Anesthetized patient—hypoxemia.
N/A
Results
Air bubbles in the arterial blood sample and/
or improper packaging of the arterial blood 
sample—falsely low PaCO2 values after 
approximately 30 min.Valid if Run in Human Laboratory?
Yes
N/A
• Arterial blood gas analysis—diagnosis 
determined from a blood sample collected in 
an anaerobic manner, as follows: use enough 
heparin to coat the needle and the inside of 
the syringe; obtain sample from femoral or 
dorsal pedal artery; place a rubber stopper on 
the needle or cover the hub of the syringe to 
prevent room air from entering the sample.
• Analyze sample within 15 minutes if left at 
room temperature; place sample on ice to 
extend time for safe and accurate analysis to 
2–4 hours.
• Bedside or portable blood gas analyzers— 
several models available; make analysis more 
convenient.
IMAGING
Thoracic radiography—may reveal bronchial, 
alveolar, or pleural space disease. Cervical 
radiography can suggest a large airway 
• Upper airway endoscopy used to rule out 
laryngeal mass or paralysis.
• Alternative method of analysis—
capnometer (see Figures 1 and 2).
• End­tidal gas (PetCO2) is almost entirely 
alveolar gas and provides nearly the same value 
Figure 1 .
Normal capnogram. The wave segment from P to Q 
is exhalation; Q to R is the plateau after exhalation; 
point R is the end tidal CO2; R to S is inhalation.40
Q R
S P0
40
0
Figure 2.
Capnogram with hypercapnia. The plateau and end 
tidal CO2 are above normal.

Canine and Feline, Seventh Edition  675
Hfor CO2 as PaCO2, which closely approximates 
the mean value of perfused alveoli.
• Advantage of capnometry—can monitor 
PaCO2 on a breath ­by­breath basis, whereas a 
blood gas sample is a finite value at a finite 
time.
• Disadvantages—tachypnea and insufficient 
tidal volume will result in falsely low PetCO2; 
PaCO2 much higher than PetCO2 with 
pulmonary thromboembolism; open thoracic 
cavity (surgery) reports falsely low PetCO2 
due to excessive dead space.
  TREATMENT
• Provide adequate alveolar ventilation.
• Anesthesia—ventilation accomplished 
manually or mechanically with anesthesia 
ventilator.
• Nonanesthetized patient with severe 
pulmonary or CNS disease—mechanical 
ventilation with critical care ventilator; 
generally requires heavy sedation.
• Supplemental oxygen—need determined by 
primary disease; providing supplemental 
oxygen without providing ventilation will 
likely not correct hypercapnia.
• Definitive treatment—treat primary cause; 
discontinue inhalation anesthesia or provide 
ventilation during anesthesia; diagnostics for 
neuromuscular disease.
Respiratory stimulants not indicated and 
rarely reverse hypoventilation.CONTRAINDICATIONS
Anesthetic drugs or other respiratory 
depressants—contraindicated with CNS 
disease if adequate ventilatory support cannot 
be provided; increased PaCO2 may result in 
dangerous elevations of intracranial pressure 
and predispose patient to herniation of the 
brainstem.
N/A
N/A
  FOLLOW-UP
• Assess effectiveness of supportive therapy 
(ventilation) and definitive treatment—
should result in decreased respiratory effort.
• Reevaluate arterial blood gas or capnometry—  
determine improvement; assess adequacy of 
Concurrent CNS disease may cause high 
intracranial pressure and predispose the patient 
to herniation of the brainstem and death.
N/A
N/A
• Hypercarbia.
• Hypoventilation.
SEE ALSO
• PaCO2 = partial pressure of carbon dioxide 
in arterial blood.
• PetCO2 = end ­tidal carbon dioxide.
Daly ML. Hypoventilation. In: Silverstein 
DC, Hopper K, eds. Small Animal Critical 
Care Medicine, 2nd ed. St. Louis, MO: 
Elsevier Saunders, 2015, pp. 86–92.
Haskins SC. Monitoring anesthetized 
patients. In: Grimm KA, Lamont LA, 
T ranquilli WJ, et al., eds. Veterinary 
Anesthesia and Analgesia, 5th ed. Ames, IA: 
Wiley ­Blackwell, 2015, pp. 100–102.
McDonell WN, Kerr CL. Respiratory system. 
In: Grimm KA, Lamont LA, T ranquilli WJ, 
et al., eds. Veterinary Anesthesia and 
Analgesia, 5th ed. Ames, IA: Wiley ­
Blackwell, 2015, pp. 513–543.
Author  Thomas K. Day
Consulting Editor  Elizabeth Rozanski(continued)  Hypercapnia

676  Blackwell’s Five-Minute Veterinary Consult  
HHyperchloremia
  BASICS
Serum chloride concentration above reference 
interval (generally >122 mEq/L in dogs and 
>129 mEq/L in cats).
• Chloride is the most abundant anion in 
extracellular fluid.
• Hyperchloremia is associated with free water 
loss or excessive NaCl intake (oral or parenteral).
• Serum chloride concentration varies 
inversely to bicarbonate concentration; high 
bicarbonate loss (i.e., vomiting or renal 
wasting) is followed by renal chloride 
resorption and hyperchloremia.
Relate to underlying cause.
Species
SIGNS
• Related to concurrent hypernatremia (i.e., 
free water loss) or underlying disorder, or both.
• Severity of neurologic signs related to 
degree of hypernatremia and rate of 
Findings
• Coma.
CAUSES
High Total Body Chloride
• Oral ingestion (salt or salt water)—rare.
• NaCl (0.9% or hypertonic) or other 
chloride salts administered IV.
Normal Total Body Chloride with Water 
Deficit
• High urinary water loss (e.g., diabetes 
insipidus).
• Low intake (e.g., no access to water).
• Insensible water loss (e.g., panting).
Low Total Body Chloride with Hypotonic 
Fluid Loss
• Urinary loss—diabetes mellitus, hypoadreno­
corticism, osmotic diuresis, postobstructive 
diuresis.
• Drugs that interfere with ability to 
concentrate urine—lithium, demeclocycline, 
and amphotericin.
• Drugs that cause renal chloride retention—
acetazolamide, ammonium chloride, 
androgens, cholestyramine, and 
spironolactone.Hyperchloremic Metabolic Acidosis
• Normal anion gap.
• Renal tubular acidosis—renal tubular 
disorders causing wasting of bicarbonate or 
low hydrogen ion secretion.
• Diarrhea causing gastrointestinal loss of 
bicarbonate and renal resorption of chloride.
• Chronic respiratory alkalosis.
  DIAGNOSIS
• Diabetes insipidus.
• Renal tubular acidosis.
• Diabetic ketoacidosis.
• Salt or salt water ingestion—rare.
A falsely high chloride concentration can 
occur with high serum concentrations of 
iodide or bromide (e.g., patients treated with 
potassium bromide) if ion ­selective electrodes 
are used for measurement.
Results
Hemoglobin and bilirubin cause falsely high 
chloride readings if colorimetric tests are 
used. Lipemia may result in an artifactual 
hyperchloremia.
Yes
• Often coupled with hypernatremia.
• Diabetes insipidus—hyposthenuria, azotemia.
• Diabetic ketoacidosis—hyperglycemia, 
ketonemia, and ketonuria.
• Dehydration—urine specific gravity 
>1.030, prerenal azotemia.
• Renal tubular acidosis—metabolic acidosis 
in the presence of alkaline urine, hypokalemia, 
other causes of metabolic acidosis (e.g., 
azotemia, hyperlactatemia, ketonemia) not 
present.
• Blood ­gas analysis—metabolic acidosis, 
may have respiratory compensation.
• Anion gap—normal if primary 
hyperchloremia or bicarbonate loss.
IMAGING
CT or MRI in patients with diabetes 
insipidus to rule out pituitary tumor.
  TREATMENT
• If hyperchloremia and hypernatremia due 
to free water loss, administer free water either orally or IV (see below); target a sodium 
concentration decrease of 12 mEq/day; serum 
sodium concentration should be rechecked 
every 4–6 hours and fluids adjusted as 
necessary to maintain appropriate rate.
• If renal tubular acidosis, treat underlying 
cause (usually pyelonephritis).
• If renal or gastrointestinal bicarbonate loss, 
administration of NaHCO3 can be 
• Sodium bicarbonate—calculate bicarbonate 
deficit (0.3 * bodyweight (kg) * 
[24 mEq – current [HCO3−] ]) and give 
⅓–½ of this dose slowly IV.
• 5% dextrose in water—calculate free water 
deficit (see hypernatremia) and administer so 
that serum sodium does not decrease by more 
than 0.5 mEq/h (or 12 mEq/day).
• Rapid correction of hypernatremia can 
cause cerebral edema.
• Hypocalcemia may develop during correction 
of serum pH, in patients with borderline low 
serum ionized calcium concentrations.
  FOLLOW-UP
Electrolytes, bodyweight, and hydration status.
Animals should always have access to water.
Rapid correction of hypernatremia can lead to 
cerebral edema.
SEE ALSO
Hypernatremia
DiBartola SP . Fluid, Electrolyte and Acid ­
Base Disorders in Small Animal Practice, 
3rd ed. Philadelphia, PA: Saunders, 2005.
Rose DB, Post T. Clinical Physiology of 
Acid­Base and Electrolyte Disorders, 5th ed. 
New York: McGraw ­Hill, 2000.
Melinda Fleming.

Canine and Feline, Seventh Edition  677
H  BASICS
OVERVIEW
• Hypercoagulability (aka thrombophilia) is 
an imbalance between procoagulant and 
anticoagulant factors that favors thrombosis.
• Thrombus formation occurs in the presence 
of endothelial injury, altered blood flow, and/
or hypercoagulability (Virchow’s triad).
• Hypercoagulability may result from platelet 
hyperaggregability, increased amounts or 
activation of clotting factors, reduced or 
inhibited anticoagulant proteins, or defective 
fibrinolysis.
• Common sites of thrombosis—pulmonary 
arteries, distal aorta, cranial vena cava, 
intestinal/mesenteric vessels, portal vein.
Depends on underlying condition.
SIGNS
• Hypercoagulability is symptomless; 
thrombosis causes site-dependent signs.
acute severe dyspnea and tachypnea.
• Arterial thromboembolism (ATE)—acute 
paresis/paralysis, limb pain (ischemic myopathy), 
decreased pulse and cold limbs; onset in dogs 
may be gradual vs. peracute in cats.
• Portal vein or caudal vena cava 
thrombosis—ascites.
(IMHA).
• Systemic inflammation.
• Cardiac disease.
• Hyperadrenocorticism or corticosteroid 
therapy.
  DIAGNOSIS
• PTE may mimic pneumonia, pulmonary 
edema, dirofilariasis.
• Distal ATE—other causes of paraparesis 
and paraplegia (e.g., neurologic).
Reflect underlying disease or effects of 
thrombosis in specific organs. Animals with 
protein-losing nephropathy have proteinuria 
and elevated urine protein : creatinine ratio, 
possibly signs of nephrotic syndrome.
• D-dimer—sensitive for fibrinolysis; thrombosis 
unlikely if normal; nonspecific for cause.• Antithrombin (AT)—decreased activity 
increases risk of thrombosis.
• Prothrombin time (PT), activated partial 
thromboplastin time (APTT)—shortened 
clotting times are unreliable markers for 
thrombophilia.
• Thromboelastography, thromboelastometry, 
rotational thromboelastometry—can 
potentially identify hypercoagulability.
• Arterial blood gas, pulse oximetry— 
hypoxemia.
IMAGING
• Ultrasonography—confirm presence of 
arterial or venous thrombi.
• Echocardiography—identify cardiac 
disease, intracardiac thrombi, or spontaneous 
echocontrast (“smoke”); pulmonary 
hypertension associated with PTE.
• Angiography (standard or CT angiography).
• Nuclear perfusion scintigraphy—can 
support diagnosis of PTE.
  TREATMENT
• Inpatient—supportive care, analgesia, 
anticoagulation.
• Supportive care—ensure hydration, 
maintain perfusion, minimize vascular stasis, 
correct and monitor acid-base and electrolyte 
abnormalities, use venous catheters 
appropriately.
• Oxygen therapy for hypoxemia.
Anticoagulants
• Unfractionated heparin for initial therapy, 
starting dose: 150–200 IU/kg SC q6-8h; 
titrate to achieve 1.5-fold increase in APTT; 
check APTT daily (4h post heparin dose).
• Low molecular weight heparin—
enoxaparin: 1 mg/kg (1,000 U/kg) SC 
q6–12h; dalteparin: 150 mg/kg SC q 6–8h. 
Monitor anti-Xa activity.
• Rivaroxaban—0.5 mg/kg PO q24h for 
chronic therapy; no reversal agents available.
• Warfarin for chronic therapy, starting dose: 
0.1–0.2 mg/kg PO q24h; adjust dose based 
on international normalized ratio.
Platelet Inhibition
• Clopidogrel—prophylaxis, prevents repeat 
thrombosis; dogs: 0.5–1 mg/kg PO q24h; 
cats: 18.75 mg PO q24h; more effective than 
aspirin in preventing recurrence of ATE in 
cats.• Aspirin—prophylaxis, after thrombosis; 
dogs: 0.5–5.0 mg/kg PO q12–24h.
Thrombolysis
• Severe side effects possible. Reperfusion 
injury is common.
• Tissue plasminogen activator (tPA)—1 mg/
kg incrementally IV once; most effective in 
first 3–6 hours after thromboembolism.
• Do not treat with warfarin initially; overlap 
with heparin therapy for 2 days.
• Reassess coagulation with any medication 
changes.
• If bleeding occurs, discontinue and 
administer protamine or vitamin K and 
plasma as indicated to correct hemorrhage.
  FOLLOW-UP
• Monitor patients for clinical signs or 
imaging evidence of resolution of thrombosis.
• Risk of future thromboembolic events.
SEE ALSO
time.
• ATE = arterial thromboembolism.
anemia.
• tPA = tissue plasminogen activator.
deLaforcade A, Bacek L, Blais MC, et al. 
Consensus on the Rational Use of 
Antithrombotics in Veterinary Critical Care 
(CURATIVE): domain 1—defining 
populations at risk. J Vet Emerg Crit Care 
2019, 29(1):37–48.
Wiinberg B, Kristensen AT. Hypercoagulable 
states. In: Bonagura JD, T wedt DC, eds. 
Kirk’s Current Veterinary Therapy XV. 
St. Louis, MO: Elsevier Saunders, 2014, 
pp. 297–301.
Consulting Editor  Melinda S. CamusHypercoagulability

678  Blackwell’s Five-Minute Veterinary Consult  
H  BASICS
OVERVIEW
• Idiopathic, persistent eosinophilia with 
infiltration of organs causing dysfunction, 
often leading to death.
• May be caused by a severe reaction to an 
unidentified antigen and/or dysregulation of 
immunologic control of eosinophilopoiesis.
• Organ damage caused by effects of 
eosinophil granule products and eosinophil-
derived cytokines that are released in tissues 
from activated and/or necrotic cells.
• Common sites of infiltration: gastrointestinal 
(GI) tract (especially intestine and liver), 
spleen, bone marrow, lung (dogs), and lymph 
nodes (especially mesenteric).
• More common in cats than dogs.
• Unclear whether HES is a distinct entity 
from eosinophilic leukemia.
• Generally poor prognosis, especially cats.
• Cats—occurs more frequently in female, 
middle-aged domestic shorthairs.
• Dogs—Rottweilers may be overrepresented.
SIGNS
• Intermittent vomiting and diarrhea.
• Thickened (diffuse or segmental) intestine 
that is often nonpainful.
• Lymphadenopathy (especially mesenteric).
• Dyspnea.
• Mass lesions caused by eosinophilic 
granulomatous inflammation and infiltration.
• Less frequently—fever, pruritus, seizures, 
thromboembolic events.
• Unknown; probably severe reaction to 
unidentified antigen.
• Cats—eosinophilic enteritis may be early form.
  DIAGNOSIS
• Reactive eosinophilia—parasitism, allergic/
hypersensitivity reactions, infectious disease, 
immune-mediated disease, fungal infections, 
neoplasia; with these conditions, eosinophilia 
usually limited in magnitude and remains 
confined to specific organ.
• Eosinophilic leukemia—differentiating 
criteria: eosinophilic leukemia tends to have 
immature eosinophils seen in higher numbers 
in circulation, constituting higher percentage 
of leukocyte differential; anemia more 
common and often more severe; 
myeloid : erythroid (M : E) ratio in bone marrow higher (>10 : 1) with more immature/
blast forms and disorderly maturation; tissue 
infiltrates consist of immature eosinophils and 
may show sinusoidal pattern in liver without 
fibrosis; in cats, chloroma-like masses in 
kidneys are reported.
• Leukocytosis with marked eosinophilia, 
possibly with left shift in eosinophil series; 
mature eosinophil count from 5,000 to 
>130,000/ μL.
• Basophilia.
• Mild anemia.
• With organ damage or dysfunction, 
associated abnormalities seen.
Rule out identifiable etiologies—fecal 
flotation, heartworm test, biopsy.
IMAGING
• Organ enlargement/infiltration may be 
visualized with survey radiographs and/or 
• Intestinal mucosal irregularities and 
thickening seen on ultrasound or contrast 
radiography.
• Bone marrow aspiration and/or core biopsy.
• Fine-needle aspirate or biopsy of affected 
tissues.
• Spleen—eosinophilic infiltrates in red pulp, 
sometimes white.
• GI tract—mucosal and submucosal 
eosinophilic infiltrates in small intestine, 
sometimes in colon and stomach.
• Bone marrow—hypercellularity, eosinophilic 
hyperplasia (up to 40% of all nucleated cells), 
unremarkable maturation and morphology with 
high M : E ratio (mean 7.27 : 1).
• Lymph nodes—reactive with eosinophilic 
infiltration.
• Other (less frequent)—eosinophilic infiltrates 
in skin, myocardium, body cavity effusions.
  TREATMENT
• Eliminate identifiable primary disease.
• Address any specific organ dysfunction/failure.
• Corticosteroids—prednisone 1–2 mg/kg/
day PO initially, then taper therapy if 
eosinophilia suppressed; if eosinophilia 
returns, resume higher daily dose.
• Imatinib mesylate approved in humans to 
treat chronic myelogenous leukemia as well as 
HES, used with possible efficacy in cats at 
9.6 mg/kg PO q24h.• Hydroxyurea—to reduce eosinophil count 
if not normal or near normal after 7–14 days 
of steroid treatment; used long term if 
effective in conjunction with steroids.
• Cyclosporine A—suppresses production of 
eosinophilopoietic factors by T cells.
• Vincristine and alkylating agents such as 
chlorambucil effective in humans.
• Reduce dosage or discontinue drugs if bone 
marrow suppression or thrombocytopenia 
develops.
• Specific drug toxicities for each agent, most 
notably myelosuppression.
• Imatinib mesylate may lead to protein-
losing nephropathy, although association 
uncertain.
  FOLLOW-UP
• Serial CBC monitoring of eosinophil count 
(not always indicative of tissue infiltrates) and 
to detect myelosuppression if myelotoxic 
drugs used.
• Monitor clinical signs and any physical 
• Other testing for specific organ function.
SEE ALSO
Eosinophilia
• M : E = myeloid : erythroid.
Lilliehook I, Tvedten H. Investigation of 
hypereosinophilia and potential treatment. 
33:1359–1378.
Consulting Editor  Melinda S. CamusHypereosinophilic Syndrome (HES)

Canine and Feline, Seventh Edition  679
HHyperestrogenism (Estrogen Toxicity)
  BASICS
OVERVIEW
• A syndrome characterized by high serum 
concentration of estrogen (estradiol, estriol, 
or estrone).
• Can occur secondary to endogenous 
estrogen secretion or exogenous admin­
istration of estrogens, such as diethylstilbestrol 
or estriol.
• Sites of endogenous estrogen production 
include ovarian follicles, follicular ovarian 
cysts, Leydig cells, and the adrenal cortex 
(zona fasciculata and reticularis); can also 
occur as a result of peripheral conversion of 
excessive androgens.
• Endogenous estrogens in females are 
responsible for normal sexual behavior and 
development and function of the reproductive 
tract; in the male, estrogens are responsible 
for Leydig cell function.
• In females, estrogens potentiate the 
stimulatory effect of progesterone in the 
endometrium and permit cervical relaxation; 
these two effects increase the risk of cystic 
endometrial hyperplasia and pyometra. In the 
male, estrogens potentiate the action of 
androgens in the prostate. Estrogens also 
increase osteoblastic activity, retention of 
calcium and phosphorus, total body protein, 
and metabolic rate.
• High serum concentration of estrogen 
provides a source of negative feedback in the 
hypothalamic ­pituitary axis, suppressing 
gonadotropin secretion, and interferes with 
stem cell differentiation in the bone marrow 
and erythrocyte iron metabolism.
Endogenous Hyperestrogenism
• Older male dog (secondary to functional 
testicular tumors).
• Older female dog (secondary to granulosa 
cell or other functional ovarian tumors, 
follicular ovarian cysts).
• Young female dog (follicular ovarian cysts).
Exogenous Hyperestrogenism
• All breeds, genders, and ages, associated 
with estrogen administration or exposure.
• Toy breed dogs are at increased risk for 
exposure to human transdermal hormone 
SIGNS
• Attractive to intact male dogs.
• Infertility.
• Prolonged proestrus and estrus (female).
• Decreased libido (male).
• Nymphomania (female).
• Variable vulvar bleeding and enlargement, 
excessive vulvar licking.• Epistaxis, hematuria (thrombocytopenia); 
lethargic, febrile (neutropenia); lethargic 
(anemia).
• Skin/endocrine—nonpruritic, symmetric 
alopecia (endocrine alopecia), hyperpig  ­ 
• Reproductive (male)—palpable testicular 
mass, testicular asymmetry (tumor and/or 
atrophy), cryptorchidism (unilateral or 
bilateral), prostatomegaly (squamous 
metaplasia), gynecomastia.
• Reproductive (female)—vulvar edema and 
enlargement, vulvar discharge, gynecomastia 
mammary gland enlargement.
• Hemic/lymphatic/immune—pale mucous 
membranes, petechia, fever, lethargy (blood 
loss).
• Follicular ovarian cysts.
• Functional ovarian tumor (granulosa cell 
tumor and other ovarian tumors).
• Testicular tumor (specifically Sertoli cell 
tumor, but also Leydig and interstitial cell 
tumors).
• Exogenous estrogen exposure.
  DIAGNOSIS
Nonpruritic, Symmetric Alopecia
• Hypothyroidism—diagnose on clinical 
signs, biochemistry, CBC, and thyroid 
function testing.
• Hyperadrenocorticism—diagnose on 
clinical signs (polyuria, polydipsia, exercise 
intolerance), CBC, serum biochemistry, 
specific testing (urine cortisol : creatinine 
ratio, adrenal function testing).
• Growth hormone–responsive dermatosis 
(breed risk: Pomeranian).
Attractive to Male Dogs
• Vaginitis, perivulvar dermatitis 
(differentiate from hyperestrogenism by lack 
of vaginal superficial epithelial cell 
predominance on vaginal cytology), lack of 
evidence of ovarian abnormalities, or 
confirmation of complete ovariohysterectomy 
or ovariectomy.
• Genitourinary tract infection, inflammation, 
foreign body, or neoplasia.
Infertility
• Testicular degeneration/atrophy/immune ­
mediated orchitis—diagnosis based on 
physical examination, lack of testicular or 
intra­abdominal masses, semen evaluation, 
and testicular biopsy or fine ­needle aspirate.
• Intersex abnormalities—uncommon; diagnosis 
supported by abnormal external genitalia, 
abnormal karyotype, and histologic examination 
of the reproductive tract, when available.CBC/BIOCHEMISTRY/URINALYSIS
• CBC—variable; initially characterized by 
thrombocytopenia or thrombocytosis, 
progressive anemia, and leukocytosis (may 
exceed 100,000 white blood cells [WBCs]/ μL); 
after 3 weeks, pancytopenia and aplastic 
anemia seen.
• Chemistry panel and urinalysis are usually 
unremarkable, but hematuria can be present 
with thrombocytopenia.
• Serum estrogen (estradiol) 
concentrations—prolonged ( >30 days) 
elevation at levels above baseline is 
responsible for clinical signs rather than the 
actual concentration; serum concentrations 
may be within normal limits, and accuracy of 
radioimmunoassay is variable.
• Vaginal and preputial cytology—extremely 
reliable as a bioassay for estrogen; under the 
influence of estrogen, cytology reveals a 
predominance of superficial epithelial cells 
that are anuclear or have pyknotic nuclei; 
preputial cytology with greater than 20% 
superficial cells is consistent with elevated 
serum estrogen.
• Evaluation for ovarian remnant syndrome 
(ORS)—anti ­Müllerian hormone (AMH) 
testing: a positive test in a bitch >6 months 
of age or >30 days from ovariohysterectomy 
supports the presence of ovarian tissue; in 
cases with negative AMH but convincing 
clinical evidence supporting ORS, some 
investigators advise measurement of serum 
progesterone to identify persistent luteal 
structures lacking AMH; the AMH test will 
differentiate between ORS and exogenous 
estrogen exposure.
• The semi ­quantitative luteinizing hormone 
(LH) assay (Zoetis), if elevated, suggests a 
lack of ovaries, but cannot differentiate 
exogenous vs. endogenous estrogen exposure 
if low.
IMAGING
metastatic neoplasia.
• Ultrasonography of the abdomen, inguinal 
canal, and testes—to assess for testicular 
masses, cystic or enlarged ovarian structures, 
intra­abdominal masses, lymphadenopathy, 
and prostatomegaly.
• Vaginoscopy to evaluate the vaginal 
mucosa; under the influence of estrogen, the 
vaginal mucosa should appear edematous 
and pink.
• Fine­needle aspiration of testicular 
masses—cytologic diagnosis prior to surgery.
• Percutaneous ultrasound ­guided aspiration 
of large ovarian follicular cysts—rarely results 
in clinical resolution (cystic structure persists); 
hormone concentration can be measured in 
the cystic fluid.

680  Blackwell’s Five-Minute Veterinary Consult  
H• Examination and aspiration/biopsy of local 
lymph nodes—for evaluation of metastatic 
disease (via ultrasound or surgical biopsy).
• Bone marrow aspirate or core biopsy—
assess myelosuppression.
• Skin biopsy—may reveal nonspecific 
changes associated with endocrine alopecia 
such as orthokeratotic hyperkeratosis, 
epidermal atrophy and melanosis, follicular 
keratosis, predominance of telogen hair 
follicles, and sebaceous gland atrophy.
  TREATMENT
• T reatment of choice in the intact or 
partially neutered female and male is surgical 
neutering; the prognosis is good if residual or 
malignant gonadal tissue can be completely 
removed.
• Unilateral orchiectomy or ovariectomy of the 
affected neoplastic testicle or cystic or neoplastic 
ovary may be considered in valuable breeding 
animals; use of testicular prosthetic devices is 
neither advised nor ethical; contralateral 
testicular changes (male) or endometrial changes 
(female) secondary to prolonged estrogen 
exposure can contribute to subfertility even if 
the abnormal gonad has been removed, with a 
guarded prognosis for fertility; histopathology 
should always be performed to evaluate for 
neoplasia and local lymphatic metastasis.
• Discontinue estrogen exposure in cases of 
exogenous hyperestrogenism; discontinue or 
reduce the dose of exogenous estrogen if used 
therapeutically; prognosis is good.
• Supportive care—including administration 
of appropriate antimicrobial therapy, IV fluids, and blood products to treat febrile 
neutropenia or anemia.
• Synthetic erythropoietin, darbopoietin, 
granulocyte colony ­stimulating factor 
(G­CSF), granulocyte ­macrophage colony ­
stimulating factor (GM ­CSF)—may be 
considered to stimulate erythroid and 
granulocytic production at the level of the 
bone marrow; lithium has reportedly been of 
benefit in cases of estrogen ­induced bone 
marrow aplasia.
• Gonadotropin ­releasing hormone (GnRH)—
unlikely to induce ovulation in cases of 
follicular cysts.
• Iron dextran to support erythrocyte 
regeneration—dog: 10–20 mg/kg (max 
300 mg/dog) IM monthly PRN; cat: 10 mg/
kg IM monthly PRN.
Chemotherapeutic agents for treatment of 
metastatic testicular or ovarian neoplasia 
should be used cautiously due to increased 
risk of bone marrow suppression. Consult 
with a veterinary oncologist.
  FOLLOW-UP
• Serial CBC analysis to evaluate response to 
therapy and progression of disease.
• Serial bone marrow cytology—to evaluate 
bone marrow response and erythroid, 
myeloid, and megakaryocytic regeneration 
when myelosuppression is chronic; peripheral 
signs of regeneration may not occur for weeks 
to months after initial insult.
• Clinical signs of male feminization 
syndrome should resolve 2–6 weeks after 
testicular tumor removal.
• Lack of resolving pancytopenia and 
continued bone marrow hypoplasia 3 weeks 
after surgical removal of ovarian or testicular neoplasia or removal of follicular cysts is 
associated with a grave prognosis.
• ORS.
• Cystic endometrial hyperplasia and 
subfertility/infertility.
• Hepatic insufficiency.
• Bone marrow aplasia, pancytopenia.
• Sepsis.
• AMH = anti ­Müllerian hormone.
• G­CSF = granulocyte colony ­stimulating 
factor.
• GM­CSF = granulocyte ­macrophage 
• GnRH = gonadotropin ­releasing  
hormone.
• ORS = ovarian remnant syndrome.
Davidson AP . Reproductive system disor­
ders. In: Nelson RW, Couto GC, eds., 
Small Animal Internal Medicine, 5th ed.  
St. Louis, MO: Elsevier, 2014,  
pp. 897–966.
Authors  Autumn P . Davidson and Sophie A. 
Grundy
available onlineHyperestrogenism (Estrogen Toxicity)  (continued)

Canine and Feline, Seventh Edition  681
H  BASICS
• Blood glucose (BG) concentration above the 
reference interval: >130 mg/dL (>7 mmol/L).
• For cats >8 years of age, BG concentration 
>189 mg/dL (10.5 mmol/L).
• Physiologic (stress hyperglycemia)—normal, 
transient response to stress, especially in cats.
• Laboratory or portable glucometer error—
anemia results in artificially high BG 
concentration with some portable glucometers.
• IV infusion of dextrose-containing fluids.
• Drugs that inhibit insulin secretion (e.g., 
dexmedetomidine).
• Diabetes mellitus (DM)—absolute or 
• Endocrine/metabolic—insulin deficiency 
causes disorders of carbohydrate, protein, and 
fat metabolism; insulin resistance occurs via 
various mechanisms.
• Renal/urologic—osmotic diuresis from BG 
exceeding renal threshold causes polyuria 
(PU) with secondary polydipsia.
• Pancreas/hepatobiliary—beta cell loss; 
endocrine hepatopathy, hepatomegaly.
• Ophthalmic—persistent hyperglycemia can 
cause cataracts in dogs.
• Nervous—severe hyperglycemia may cause 
CNS dehydration from high serum osmolality; 
diabetic neuropathy in cats causes hind limb 
weakness and plantigrade, ± palmigrade, gait; 
other neuropathies are also possible (e.g., 
Horner’s syndrome).
GENETICS
Breed predispositions indicate likely genetic 
influences for DM in dogs and cats.
Prevalence of DM in hospital populations is 6 
in 1,000 cats and 3 in 1,000 dogs.
Species
Onset of DM typically occurs after 5 years of 
age; highest prevalence from 8–12 years of age.
Neutered males (cats and dogs) and intact 
females (dogs) are predisposed to DM.
SIGNS
• DM—signs have insidious onset over weeks 
to months.
• Animals with concurrent disease, such as 
pancreatitis, might not show “classic” signs of 
hyperglycemia.Historical Findings
• Polydipsia and PU—PU might manifest as 
inappropriate urination or urinary 
• Weight loss with normal or increased 
appetite.
• Vision loss due to diabetic cataracts  
(dogs).
• Weak plantigrade gait due to diabetic 
neuropathy (cats).
• Previous overweight/obesity (especially cats 
and intact female dogs).
• Severe hyperglycemia can cause decreased 
mentation, coma.
• Obese, normal, or underweight.
• Sarcopenia.
• Plantigrade ± palmigrade gait (cats).
• Cataracts (dogs).
• Chronic infections—respiratory, skin, 
• Poor hair coat.
• Ketotic or sweet odor to breath.
• Separation of incisors, broadening of the 
face, and organomegaly in cats with 
hypersomatotropism.
CAUSES
• DM—a heterogeneous group of diseases 
characterized by hyperglycemia resulting from 
inadequate insulin secretion, inadequate 
insulin action, or both.
• Inadequate insulin action (insulin 
resistance) is associated with hyperadreno -
corticism, pheochromocytoma, glucagonoma, 
hypersomatotropism, hyper- and hypothy-
roidism, high progesterone during diestrus 
(dogs), and drugs (e.g., thiazide diuretics, 
progestogens [e.g., megestrol acetate], growth 
hormone, topical and systemic corticoster-
oids, and dexmedetomidine.
• Chronic hyperglycemia (glucose toxicity) 
can cause insulin resistance.
• Breed predispositions for DM vary with 
geographic region.
• Older age.
• Obesity.
• Sedentary/indoor lifestyle.
• Stress.
• Concurrent disease, particularly hyper-
adrenocorticism, hypersomatotropism, 
• Diestrus in dogs.
• Diabetogenic drugs—corticosteroids, 
progestogens.
• Dextrose-containing fluids.  DIAGNOSIS
• Stress hyperglycemia—differentiated from 
DM by documentation of persistent fasting 
hyperglycemia for more than 24 hours, or 
increased serum glycated protein concen  trations.
• DM.
• Diagnosis of DM in cats:
 ◦Random (fasted or unfasted) BG 
≥270 mg/dL (15 mmol/L) with clinical signs 
of hyperglycemia (with no other plausible 
cause) or hyperglycemic crisis and at least 
one of the following: increased serum 
glycated protein concentrations; glycosuria 
on more than one occasion on a voided 
sample acquired in a home environment at 
least 2 days after any stressful events.
 ◦Random (fasted or unfasted) BG between 
130 and 270 mg/dL (7–15 mmol/L) and at 
least two of the following: clinical signs of 
hyperglycemia or hyperglycemic crisis; 
increased serum glycated protein concentra-
tions; glycosuria on more than one occasion 
on a voided sample acquired in a home 
environment at least 2 days after any 
stressful events.
• Diagnosis of DM in dogs:
 ◦Fasted or unfasted BG ≥200 mg/dL 
(11 mmol/L) with clinical signs of 
hyperglycemia or hyperglycemic crisis.
 ◦Fasting BG 130–200 mg/dL 
(7–11 mmol/L) with or without clinical signs 
of hyperglycemia or hyperglycemic crisis.
• DM is likely when hyperglycemia occurs in 
combination with ketosis and/or ketonuria.
Factors That May Alter Laboratory Results
• Delayed serum or plasma separation lowers 
glucose concentration; glucose concentration 
should be measured within 30 minutes of 
collection; whole blood samples collected in 
fluoride oxalate anticoagulant may be stored.
• Lipemia, hemolysis, and icterus may 
interfere with spectrophotometric assays.
• Glucometers intended for human use tend 
to underestimate the true BG in cats and 
dogs; wide variability in the accuracy of 
different meters necessitates correlation of 
results from each meter with results from a 
veterinary diagnostic laboratory prior to use.
• Veterinary-specific glucometers provide more 
accurate results than human glucometers.
• BG reagent strips require whole blood, 
must be stored correctly, and be in date.
• Hyperglycemia might be the only abnormal 
finding.
• For findings associated with DM, see 
specific chapters.Hyperglycemia

682  Blackwell’s Five-Minute Veterinary Consult  
HOTHER LABORATORY TESTS
• Fructosamine concentration identifies degree 
of glycemia over the previous 2–3 weeks; results 
are assay dependent and may be affected by 
hemolysis or lipemia; provides no information 
on variability of BG concentrations.
• Glycosylated hemoglobin concentration 
identifies degree of glycemia over the previous 
10 weeks (cats) or 16 weeks (dogs); provides no 
information on variability of BG concentrations.
stimulation test or low-dose dexamethasone-
suppression test to diagnose hyperadrenocor-
ticism in dogs; false-positive results might be 
obtained if there is poor diabetic control.
• Serum insulin-like growth factor 1 (IGF-1) 
assay to diagnose hypersomatotropism in cats; 
false-negative results are more likely when 
there is severe insulin deficiency; cats should 
be treated with insulin for 4–6 weeks prior to 
testing.
  TREATMENT
• Stress hyperglycemia is self-limiting.
• Diabetic cats and dogs that are eating 
well—outpatient management.
• Those that are unwell, inappetent, or have 
other signs such as vomiting require inpatient 
management with insulin and IV fluids.
• Concurrent disease can compromise DM 
management and should be promptly 
diagnosed and treated.
Glucose monitoring is recommended for all 
hospitalized hyperglycemic patients. Venous 
or capillary blood testing using a veterinary 
glucometer is appropriate. Real-time 
continuous glucose monitoring systems 
(CGMS) or flash glucose monitoring systems 
(FGMS) can simplify glucose monitoring of 
hospitalized patients.
ACTIVITY
Activity does not need to be limited in dogs 
and cats with DM and may decrease insulin 
requirement in working diabetic dogs.
DIET
• See relevant chapters on DM.
• Nutritional requirements for concurrent 
diseases take precedence over nutritional 
requirements for DM; good diabetic control 
can be achieved with insulin treatment 
regardless of diet.
• Client education is critical, because most 
treatment and monitoring of a diabetic patient 
will be done by the owner at home, and 
clinical signs will guide treatment decisions.
• Owner concerns relating to the impact that 
treating their pet will have on their lifestyle 
should be addressed.SURGICAL CONSIDERATIONS
• Approximately 8% chance of diabetic 
remission following neutering and insulin 
therapy in female dogs; those that do not 
achieve remission generally have improved 
diabetic control.
• Improved diabetic control and possibly 
remission will occur following hypophysectomy 
in cats with hypersomatotropism; however, this 
treatment is expensive with limited availability.
• Exogenous insulin is the mainstay of 
treatment of DM.
• See chapters on DM.
• Drugs that cause insulin resistance (e.g., 
systemic or topical corticosteroids) should be 
used with caution in hyperglycemic animals; 
an increased insulin dose may be necessary.
Concurrent use of insulin and oral 
hypoglycemic agents might lead to 
• Glipizide and acarbose.
  FOLLOW-UP
• Animals in diabetic remission require 
ongoing monitoring for recurrence of 
• Minimize use of diabetogenic drugs, 
particularly in susceptible individuals.
• Prevent obesity in cats and intact female dogs.
• Neuter female dogs at risk of developing DM.
• Severe hyperglycemia may be associated 
with CNS depression and coma because of 
hyperosmolality.
• Diabetic cataracts (dogs).
• Diabetic neuropathy in cats with poor 
• Insulin-induced hypoglycemia.
• T ransient stress hyperglycemia is self-limiting.
• T reatment of DM often is associated with 
an excellent prognosis, and typically results in 
a very good quality of life and similar life 
expectancy to animals without diabetes.  MISCELLANEOUS
• Hyperosmolality.
• Hypersomatropism.
• In intact bitches, a form of diabetes 
analogous to human gestational diabetes can 
occur during diestrus or pregnancy; if insulin 
therapy is initiated promptly, diabetic 
remission can sometimes be achieved 
following spay or whelping.
• Increased incidence of dystocia (large fetal 
size) and hypoglycemia in neonates when 
hyperglycemia has been present during 
SYNONYMS
High blood sugar.
SEE ALSO
• Diabetes Mellitus with Ketoacidosis.
Cats.
Dogs.
• CGMS = continuous glucose monitoring 
system.
• FGMS = flash glucose monitoring system.
• IGF-1 = insulin-like growth factor 1.
https://esve.org/alive/search.aspx
Behrend E, Holford A, Lathan P , et al. AAHA 
diabetes management guidelines for dogs 
and cats. J Am Anim Hosp Assoc 2018, 
54(1):1–21.
Reeve-Johnson MK, Rand JS, Vankan D, 
et al. Cutpoints for screening BG 
concentrations in healthy cats. J Fel Med 
Surg 2017, 19(12):1181–1191.
Sparkes AH, Cannon M, Church D, et al. 
Fel Med Surg 2015, 17:235–250.
Thompson A, Lathan P , Fleeman L. Update 
on insulin treatments for dogs and cats: 
insulin dosing pens and more. Vet Med Res 
Reports 2015, 6:129–142.
Authors  Linda M. Fleeman and Sarah B. 
Pierard
Consulting Editor  Patty A. LathanHyperglycemia  (continued)

Canine and Feline, Seventh Edition  683
HHyperkalemia
  BASICS
Serum potassium concentration higher than 
the testing laboratory’s upper limit of normal, 
generally >5.7 mEq/L (mmol/L).
• Potassium is primarily intracellular; serum 
concentrations do not accurately reflect tissue 
concentrations. • Hyperkalemia is often 
associated with cellular injury (e.g., trauma and 
ischemia) and other causes of translocation of 
potassium out of the intracellular space (e.g., 
acidosis). • Potassium is eliminated in the 
kidneys and elimination is enhanced by 
aldosterone; conditions that inhibit renal 
elimination of potassium will cause hyperkalemia.
• Cardiovascular—potassium affects cardiac 
conduction, and changes are reflected on the 
ECG; as potassium rises, the T waves become 
tall and spiked with a narrow base, the QRS 
complexes widen, and the P–R intervals 
lengthen; the P waves become smaller and wider 
and, in animals with severe hyperkalemia, 
disappear (atrial standstill); higher concentrations 
of potassium cause fusion of the QRS–T, which 
causes a wide complex idioventricular brady­
arrhythmia followed by ventricular fibrillation or 
asystole; ECG changes in animals with 
hyperkalemia vary and are diminished by 
hypernatremia, hypercalcemia, and alkalosis. 
• Nervous—neuromuscular weakness.
• Dog and cat. • Pseudohyperkalemia in 
certain East Asian dog breeds (e.g., Akita, 
Shiba, Jindo, and Chinese Shar ­Pei).
SIGNS
• Weakness. • Collapse. • Stranguria, 
pollakiuria, pigmenturia (animals with urethral 
obstruction). • Flaccid paralysis. • Death.
• In addition to historical findings, arrhythmias, 
especially bradyarrhythmias. • Firm, non­
expressible urinary bladder, abdominal pain in 
animals with urethral obstruction. • Abdominal 
fluid wave, distended abdomen in patients with 
urinary bladder rupture.
CAUSES
• Pseudohyperkalemia—some blood cells 
(generally reported in red blood cells [RBCs] of 
East Asian dog breeds including Akita, Shiba, 
Jindo, and Chinese Shar ­Pei; also platelets and 
white blood cells [WBCs] in any breed) contain 
high concentrations of potassium; if the blood 
sample is not analyzed or separated promptly, this 
intracellular potassium is released into the serum, 
causing the potassium concentration to be 
artificially high (pseudohyperkalemia); seen in 
patients with thrombocytosis or severe leuko­
cytosis. • Low potassium elimination—anuric or 
oliguric renal failure; hypoadreno  corticism; renal hypoperfusion; urinary tract rupture or urethral 
obstruction; administration of potassium ­sparing 
diuretics, angiotensin ­converting enzyme (ACE) 
inhibitors, trimethoprim, nonsteroidal anti ­
inflammatory drugs, or heparin (causing 
hypoaldosteronism); some gastrointestinal 
diseases (e.g., salmonellosis, trichuriasis). 
• T ranslocation of potassium—metabolic 
acidosis, reperfusion syndrome, thrombolysis in 
feline aortic thromboembolism, tumor lysis 
syndrome, muscle injury (trauma, phosphofruc ­
tokinase deficiency), digitalis overdose, infusion 
of mannitol and hyper  glycemia (causing 
hyperosmolality). • High potassium intake—oral 
or parenteral potassium supplements or 
potassium bromide toxicosis. • Miscellaneous—
third space fluid accumulation (e.g., pleural 
effusion, ascites).
• IV fluid therapy with excessive potassium 
supplementation. • Administration of potassium ­ 
sparing diuretics (e.g., spironolactone) and 
ACE inhibitors (e.g., enalapril, benazepril), 
primarily in patients with renal disease. 
• Hypoadrenocorticism. • T rauma. • Renal 
disease. • Lower urinary tract disease including 
cystic calculi. • Thrombocytosis and leukemia. 
• Akita, Shiba, Jindo, and Chinese Shar ­Pei—
pseudohyperkalemia; not all animals within a 
breed are at risk for pseudohyperkalemia; 
approximately 20% of Akitas have the high 
potassium phenotype. • Phosphofructokinase 
deficiency. 
  DIAGNOSIS
• Waxing and waning history of gastrointestinal 
complaints, weakness, collapse—consider 
hypoadrenocorticism. • Straining to urinate or 
low urine output—consider urinary 
obstruction or oliguric/anuric renal failure.
Results
Thrombocytosis ( >1,000,000 cells/mm3), 
leukocytosis ( >200,000 cells/mm3), and 
abnormal (leukemic) leukocytes can cause release 
of large amounts of potassium into the serum.
• In patients with Na : K ratio <27, consider 
hypoadrenocorticism; some patients with 
metabolic acidosis due to diarrhea or renal 
tubular acidosis, ascites, chylothorax, or 
pregnancy may also have a low Na : K ratio. 
• In patients with azotemia, consider 
hypoadrenocorticism, anuric or oliguric renal 
failure, and ruptured or obstructed urinary 
tract. • In patients with high creatine kinase, 
aspartate aminotransferase, and lactic 
dehydrogenase, consider muscle injury. • In 
patients with severe thrombocytosis or 
leukocytosis or if the patient is an East Asian 
dog breed, consider pseudohyperkalemia.OTHER LABORATORY TESTS
stimulation test—patients with hypoadreno­
corticism generally have undetectable 
(<0.2  μg/dL) baseline and poststimulation 
IMAGING
• Radiographic contrast studies or ultrasound 
to rule out urinary tract rupture or obstruction. 
• Ultrasonography to evaluate urinary tract, 
adrenal gland size, presence of third ­space 
  TREATMENT
• Varies, depending on the underlying cause 
of hyperkalemia. • Aggressiveness is dictated 
by patient’s appearance and severity of ECG 
abnormalities. • Initiate supportive measures 
to lower potassium while pursuing definitive 
diagnosis. • Isotonic crystalloid fluids can be 
used to treat hypovolemia and will help 
decrease serum potassium; however, other 
treatments (see below) more rapidly decrease 
potassium concentration or blunt the effects 
on the heart; fluids can be administered in 
bolus doses of 20–30 mL/kg to effect; 
patients with primary cardiac disease or 
anuric renal failure may not tolerate large 
volumes of IV fluids (susceptible to volume 
overload). • Reduced potassium diet in 
animals with hyperkalemia secondary to 
chronic renal disease. • In patients with renal 
or postrenal oligo ­anuria, urine flow must be 
restored emergently, either through relief of 
obstruction or restoration of urine production 
(see Urinary T ract Obstruction). • Hemodialysis 
may be necessary in patients with oligo ­anuric 
• For patients with life ­threatening hyper­
kalemia, administer calcium gluconate 10% 
(0.5–1 mL/kg slow IV over 10 min) while 
monitoring the ECG; calcium antagonizes 
the effect of potassium on cardiac conduc ­
tion without lowering the serum potassium 
concentration. • To decrease serum 
potassium: ◦ Regular insulin (0.25–0.5 U/
kg IV) with dextrose (0.5 g/kg IV) activates 
Na+/K+ ATPase to move potassium into cells; 
may require additional supplementation of 
dextrose (e.g., 2.5% dextrose added to IV 
fluids). ◦ Dextrose (0.5 g/kg IV) can be 
used without insulin for mild hyperkalemia. 
◦ Sodium bicarbonate (1 mEq/kg slow IV) 
induces exchange of potassium for hydrogen

induces exchange of potassium for hydrogen 
ions, moving potassium into cells. ◦ Albuterol 
(1–2 puffs from inhaler) activates beta 
receptors and Na+/K+ ATPase to move 
potassium into cells.

684  Blackwell’s Five-Minute Veterinary Consult  
H
• Avoid IV fluids with high concentrations 
(>10 mEq/L) of potassium and fluids that 
cause hyponatremia, acidosis, or hypocalcemia. 
• Avoid drugs that contain potassium or 
interfere with potassium elimination (e.g., 
ACE inhibitors, trimethoprim antibiotics, 
potassium ­sparing diuretics) or interfere with 
renal function (e.g., nonsteroidal anti ­inflam­
matory drugs).
• Kayexalate and sodium bicarbonate cause a 
sodium load that may lead to fluid retention 
in patients with cardiac or renal failure. 
• Sodium bicarbonate lowers ionized calcium 
levels—use cautiously in hypocalcemic 
patients. • Sodium bicarbonate elevates blood 
carbon dioxide concentration—use cautiously 
in patients with hypoventilation.
Patiromer and sodium zirconium cyclosilicate 
are recently approved agents that bind 
potassium within the intestinal tract, limiting 
absorption and reabsorption; rarely used in veterinary practice; may have application in 
chronic hyperkalemia.
  FOLLOW-UP
• Recheck potassium at frequency dictated by 
the underlying disease. • Continuous ECG 
monitoring until rhythm disturbances resolve.
• Monitor potassium in patients receiving 
drugs that alter potassium elimination. • The 
maximum rate of IV potassium administration 
is 0.5 mEq/kg/h, and should be used only in 
the face of severe hypokalemia (average 
supplementation rate is between 0.05 and 
0.2 mEq/kg/h in patients without acute renal 
disease).
• Prolonged hypoglycemia following insulin 
administration. • Death of animals with 
severe hyperkalemia.  MISCELLANEOUS
Combined hyperkalemia and hyponatremia 
may be seen in pregnant dogs due to third ­ 
space fluid accumulation in the uterus.
SEE ALSO
• Acidosis, Metabolic. • Acute Kidney Injury. 
• Atrial Standstill. • Hypoadrenocorticism 
(Addison’s Disease). • Phosphofructokinase 
Deficiency. • Urinary T ract Obstruction.
Kogika MM, deMorais HA. A quick reference 
on hyperkalemia. Vet Clin North Am Small 
Anim Pract 2017, 47(2):223–228.
Consulting Editor  Patty A. LathanHyperkalemia  (continued)
K > 5.7 mEq/L
K > 5.7 mEq/LHistory; R/O potassium supplementation or treatment with any drugs that can
elevate potassium (ACE inhibitors, potassium sparing diuretics, nonsteroidal
anti-inflammatory drugs, digitalis, mannitol, succinylcholine)
Physical examination; R/O urethral obstruction and evaluate for possibility of
urinary tract ruptur e
Is value > 7.0 or patient showing signs or ECG 
changes consistent with hyperkalemia
YES
Evaluate CBC, serum
chemistry profile, and
urinalysis
Elevated CK,
AST, LDHNone of theseNa:k < 27 or
unexplained
hyperkalemiaAzotemiaHypercholoremic
acidosis (normal
anion gap)
R/O
translocatio n
secondar y
to acidosi sCheck urine
specific
gravityACTH
response
testR/O muscle
trauma, tumor lysis
syndrome,
reperfusion post -
thrombolysis
Depressed
response: R/O
Addison’s disease
or prior
corticosteroi d
therapyNormal or
exaggerated
responses: R/O
gastrointestinal
disease (recheck
when signs resolve),
primary
hypoaldosteronism
Measure
aldosterone
following ACTH
stimulation
Decreased
aldosterone: R/O
primary
hypoaldosteronismR/O pleural or abdominal effusion,
hyperosmolality [hyperglycemia]
pseudohypoadrenocorticism,
hyperkalemic periodic paralysi s
Recheck after effusions resolved.
Recheck after hyperosmolality corrected.
Challenge with low-dose oral KCISpecific gravity >
1.029 (dog) or
1.034 (cat) R/O
prerenal causes
and post-renal
obstruction or tearSpecific gravity <
Addison’s disease,
oliguric or anuric
renal failureRepeat with lithium heparin
plasma to rule-out
pseudohyperkalemia (acute,
severe thrombocystosis or
leukocytosis) and lab erro rNO
Figure 1 .
Algorithm for diagnosing hyperkalemia.

Canine and Feline, Seventh Edition  685
H  BASICS
• Increased concentration of lipid in the 
blood of a fasted ( >12 hours) patient; 
includes hypercholesterolemia, hypertri­
glyceridemia, or both.
• Lipemia—serum or plasma separated from 
blood that contains an excess concentration 
of triglycerides ( >200 mg/dL).
• Lactescence—opaque, milk ­like appearance 
of serum or plasma that contains an even 
higher concentration of triglycerides 
(>1,000 mg/dL) than lipemic serum.
Primary Hyperlipidemia
• Primary (idiopathic) hyperlipidemia—defect 
in lipid metabolism causing hypertriglyceridemia 
with or without hyperchylomicronemia; likely 
hereditary in miniature schnauzer, but the 
genetic defect has yet to be determined.
• Idiopathic hyperchylomicronemia in cats— 
familial, autosomal recessive defect in 
lipoprotein lipase activity.
• Primary hypercholesterolemia—occurs in 
some families of briard, rough collie, Shetland 
sheepdog, Doberman pinscher, and 
Rottweiler; low ­density lipoprotein (LDL) 
cholesterol is high.
Secondary Hyperlipidemia
• Postprandial—absorption of chylomicrons 
from the gastrointestinal tract occurs 30–60 
minutes after ingestion of a meal containing 
fat; may increase serum triglycerides for up to 
12 hours.
• Diabetes mellitus—low lipoprotein lipase 
(LPL) activity; high synthesis of very ­low­
density lipoprotein (VLDL) by the liver.
• Hypothyroidism—low LPL activity and 
lipolytic activity by other hormones (e.g., 
catecholamines); reduced hepatic degradation 
of cholesterol to bile acids.
• Hyperadrenocorticism—increased synthesis 
of VLDL by the liver and low LPL activity 
causes both hypercholesterolemia and 
hypertriglyceridemia.
• Cholestatic liver disease—hypercholester ­
olemia caused by reduced excretion of 
cholesterol in the bile.
• Nephrotic syndrome—upregulation 
of common synthetic pathway for albumin 
and cholesterol and possibly low oncotic 
pressure lead to increased cholesterol synthesis.
• Pancreatitis—associated with hypertri­
glyceridemia in dogs, especially miniature 
• Obesity—excessive hepatic synthesis 
of VLDL.
Drug-Induced Hyperlipidemia
• Glucocorticoids.• Megestrol acetate (cat).
• Nervous.
• Variable, depending on the cause.
• Hereditary hyperlipidemias—age of onset 
is >8 months in cats and >4 years in 
predisposed breeds of dog such as the 
SIGNS
• Asymptomatic.
• Recent ingestion of a meal.
• Seizures, neurologic signs.
• Abdominal pain and distress.
• Neuropathies.
• Lipemia retinalis.
• Lipemic aqueous.
• Neuropathy.
• Cutaneous xanthomata.
• Lipid granulomas in abdominal organs.
CAUSES
Increased Absorption of Triglycerides or 
Cholesterol
Postprandial
Increased Production of Triglycerides or 
• Defects in lipid clearance enzymes or lipid 
carrier proteins.
• Idiopathic hyperchylomicronemia.
• Hyperchylomicronemia in cats.
Decreased Clearance of Triglycerides or 
• Cholestasis.
• Obesity.
• High dietary intake of fats.
• Genetic predisposition in miniature 
schnauzer and Himalayan cat.
• Idiopathic hypercholesterolemia observed 
in families of briard, rough collie, Shetland 
Rottweiler.  DIAGNOSIS
Fasting Hyperlipidemia
Rule out postprandial lipemia with a 12 ­hour 
fast.
Primary Hyperlipoproteinemia
• Idiopathic hyperlipidemia is observed most 
commonly in the miniature schnauzer breed.
• Hyperchylomicronemia in cats often manifests 
as polyneuropathies and lipogranulomas.
• Idiopathic hypercholesterolemia is observed 
in a variety of breeds; animals are often 
• Hepatic disease and cholestatic disorders.
Sample Handling
• Submit serum.
• Lipemia causes hemolysis if serum remains 
with red blood cells for a long time; inquire 
about the laboratory method of clearing 
lipemic samples before submission.
• T wo samples may be submitted—one for 
biochemical analysis, which may be cleared, 
and one for triglycerides and cholesterol 
• Corticosteroids.
• Phenytoin.
• Prochlorperazine.
• Thiazides.
• Phenothiazines.
Results
• Falsely high cholesterol.
• Nonfasted samples ( <12 hours).
• Icterus—spectrophotometric techniques.
• Fluoride and oxalate anticoagulants—
enzymatic techniques.
• Lipemia.
Yes
• Results of hemogram usually normal.
• High serum triglyceride concentration—
dogs: >150 mg/dL; cats: >100 mg/dL.
• High serum cholesterol concentration—
dogs: >300 mg/dL; cats: >200 mg/dL.
• Serum biochemistry may reveal 
abnormalities consistent with causes of 
secondary hyperlipidemia.Hyperlipidemia

686  Blackwell’s Five-Minute Veterinary Consult  
H• Results of urinalysis often normal; 
proteinuria if nephrotic syndrome present.
• High ­density lipoprotein (HDL) and 
LDL determinations—used in human 
medicine; values reported for HDL and 
LDL in dogs and cats cannot be assumed 
to be reliable.
• Chylomicron test—obtain serum sample 
after a 12 ­hour fast and refrigerate for 12–14 
hours; do not freeze; chylomicrons rise to the 
surface and form a creamy layer.
• Lipoprotein electrophoresis—separates 
LDL, VLDL, and HDL1 and HDL2 
subfractions.
• LPL activity—collect serum for triglycerides 
and cholesterol concentrations and 
lipoprotein electrophoresis before and 15 
minutes after administration of heparin 
(90 IU/kg, IV); if there is no change in values 
before and after heparin administration, a 
defective LPL enzyme system should be 
• Definitive diagnostics for hypothyroidism 
or hyperadrenocorticism, if suspected.
  TREATMENT
Diet should contain <10% fat (e.g., Royal 
Canin® Low Fat; Hill’s Prescription Diet r/d®, 
w/d®, and i/d® Low Fat; Purina® OM).
Initial management is dietary; omega ­3 fatty 
acids, fibrates, and then niacin are added to 
refractory cases.
• Gemfibrozil 10 mg/kg PO q12h; cats and 
dogs.
• Bezafibrate 4–10 mg/kg PO q12h; dogs 
only.• Fish oils—omega ­3 polyunsaturated fat 
50–300 mg/kg PO q24h; dogs only.
• Niacin 50–200 mg/dog/day PO (slow 
release); dogs only.
  FOLLOW-UP
• Keep serum triglyceride concentrations 
<500 mg/dL to avoid possibly fatal episodes 
of acute pancreatitis.
• Monitoring serum cholesterol concentrations 
often is not necessary because hypercholester ­
olemia is not associated with clinical signs.
• Monitor alanine aminotransferase (ALT) 
and alkaline phosphatase (ALP) enzyme 
activities when using a fibrate and/or niacin, 
as toxicity may occur.
• Pancreatitis and seizures are common 
complications of hyperlipidemia in the 
• In cats with hereditary chylomicronemia, 
xanthoma formation, lipemia retinalis, and 
neuropathies have been reported; peripheral 
neuropathies usually resolve 2–3 months after 
institution of a low ­fat diet.
None
Potential cause of high cholesterol.
SYNONYMS
• Lipemia—turbid serum or plasma 
secondary to significant hypertriglyceridemia.• Hyperlipoproteinemia—increased blood 
concentration of lipoproteins.
SEE ALSO
Cats.
Dogs.
• HDL = high ­density lipoprotein.
• LDL = low ­density lipoprotein.
• LPL = lipoprotein lipase.
• VLDL = very ­low­density lipoprotein.
Barrie J, Watson TOG. Hyperlipidemia. In: 
Bonagura JD, ed., Kirk’s Current Veterinary 
Therapy XII. Philadelphia, PA: Saunders, 
1995, pp. 430–434.
Ford R. Canine hyperlipidemias. In: Ettinger 
SJ, Feldman EC, eds., Textbook of 
Veterinary Internal Medicine, 4th ed. 
Philadelphia, PA: Saunders, 1994, pp. 
1414–1418.
Jones B. Feline hyperlipidemias. In: Ettinger 
1410–1413.
Xenoulis PG, Steiner JM. Lipid metabolism 
and hyperlipidemia in dogs. Vet J 2010, 
183(1):12–21.
available onlineHyperlipidemia  (continued)

Canine and Feline, Seventh Edition  687
H  BASICS
• Dogs—serum magnesium >2.51 mg/dL; 
ionized magnesium >0.58 mmol/L.
• Cats—serum magnesium >2.99 mg/dL; 
ionized magnesium >0.65 mmol/L.
• Hypermagnesemia is less clinically 
significant than low total body magnesium in 
veterinary patients.
• Magnesium is second only to potassium as 
the most abundant intracellular cation. 
Found primarily in bone and muscle, it is 
required for many metabolic functions.
• Serum magnesium is present in three 
forms—protein-bound form (approximately 
25–30%) and chelated and ionized forms 
(together account for 70–75%).
• Magnesium absorption occurs primarily in 
the ileum, but also in the jejunum and colon.
• Magnesium is an important cofactor in the 
sodium-potassium ATPase pump that 
maintains electrical gradients across 
• Interference with the electrical gradient can 
change resting membrane potentials; 
repolarization disturbances result in 
neuromuscular and cardiac abnormalities.
• The kidneys maintain magnesium balance 
with 10–15% reabsorbed in the proximal 
tubule, 60–70% in the thick ascending limb 
of the loop of Henle, and 10–15% reabsorbed 
in the distal convoluted tubule. Reabsorption 
within the distal convoluted tubule is under 
hormonal and neurohormonal control and 
determines the final urine concentration of 
magnesium.
• Any condition that severely lowers the 
glomerular filtration rate can elicit hyper -
magnesemia because magnesium homeostasis 
is largely controlled by renal elimination.
• Clinically significant hypermagnesemia is 
more commonly associated with acute 
kidney injury, and the degree of hyper -
magnesemia is proportional to the severity 
of renal failure.
• Exuberant supplementation of magnesium 
can lead to iatrogenic hypermagnesemia, 
especially in patients with decreased renal 
function.
• High magnesium concentration impairs 
transmission of nerve impulses and decreases 
postsynaptic responses at the neuromuscular 
junction. When magnesium was given to 
anesthetized dogs at 0.12 mEq/kg/min, 
cardiovascular effects were not noted until 
plasma levels exceeded 12.2 mEq/L. The total 
dose of magnesium required to reach that 
level was 1–2 mEq/kg. It took cumulative 
doses of 5.9–10.9 mEq/kg to cause fatal 
cardiac arrhythmias (ventricular fibrillation).• Magnesium has been called nature’s calcium 
blocker; the most serious complications of 
hypermagnesemia result from calcium 
antagonism in the cardiac conduction system.
• Nervous.
Increased plasma ionized magnesium 
concentration was found in 2% of 9,950 
canine submissions to a clinical laboratory. In 
that study, 40% of the cases were caused by 
azotemia, 19% were iatrogenic, 11% had 
tissue damage, and 6% had endocrine disease. 
In another study, hypermagnesemia was found 
in 18% of hospitalized cats and 13% of 
hospitalized dogs. Most of these patients also 
had renal insufficiency or postrenal azotemia.
N/A
Species
N/A
SIGNS
• Usually caused by renal failure; clinical signs 
might be referable to azotemia and renal 
insufficiency. Clinical hypermagnesemia is 
reported most often in patients with preexisting 
renal disease that are oversupplemented with 
parenteral magnesium salts.
• Characterized by progressive loss of 
neuromuscular, respiratory, and cardiovascular 
function.
Findings
• Nausea, vomiting, weakness, bradycardia, 
flaccid paralysis, mental depression, and hypo-  
reflexia (including menace and palpebral reflex).
• Hypotension and ECG changes, including 
delayed intraventricular conduction and 
prolonged QT interval.
• Atrioventricular block, respiratory 
depression, coma, and cardiac arrest have 
been observed in humans with serum 
magnesium concentrations >16 mg/dL.
CAUSES
• Intestinal hypomotility disorders and 
• Endocrine disorders including hypoadreno-
corticism, hypothyroidism, and hyper- 
parathyroidism.
• Combined angiotensin-converting enzyme 
inhibitors and spironolactone administration.
• Excessive magnesium administration from 
magnesium-containing cathartic solutions given in conjunction with activated charcoal, 
magnesium-containing laxatives, and excess 
magnesium in peritoneal dialysis solutions.
• Iatrogenic oversupplementation, especially 
in patients with concurrent renal disease.
• Intestinal hypomotility.
• Massive hemolysis.
• Patients receiving angiotensin-converting 
enzyme inhibitors and spironolactone 
• Excessive use of magnesium-containing 
cathartic solutions, especially in patients with 
renal insufficiency.
  DIAGNOSIS
• Signs are most similar to those of hypocal-
cemia, which often occurs simultaneously.
• Bradycardia can be caused by neurologic 
disease, hyperkalemia, hypertension, hypo -
thyroidism, sick sinus syndrome, and various 
drugs.
Note:  12 mg of magnesium = 1 mEq of 
magnesium; to convert from mg/dL to 
mEq/L, divide by 1.2.
• Serum is favored over plasma because the 
anticoagulant used for plasma samples can 
contain citrate or other ions that bind 
• EDTA, sodium fluoride-oxalate, sodium 
citrate, and intravenous calcium gluconate can 
cause falsely low serum magnesium values.
Results
• Hemolysis can result in falsely increased 
serum magnesium; the magnesium 
concentration in erythrocytes is 
approximately three times that in serum.
• Storage of serum or urine in metal containers 
can falsely elevate magnesium values.
• Hyperbilirubinemia can cause falsely 
decreased serum magnesium.
Yes
• Serum magnesium—dogs: >2.5 mg/dL; 
cats: >2.99 mg/dL.
• Hypocalcemia is common.
• Azotemia in some patients.Hypermagnesemia

688  Blackwell’s Five-Minute Veterinary Consult  
• Ionized magnesium can be measured with 
an ion-selective electrode or by ultrafiltration 
of plasma; alternative methods of evaluating 
magnesium status include mononuclear blood 
cell magnesium levels or quantifying retention 
from a loading dose.
• Ionized hypermagnesemia is characterized 
as >0.58 mmol/L in dogs and >0.65 mmol/L 
in cats, but may vary slightly with the 
analyzer.
• Electrodiagnostics (e.g., electromyelography 
and electrocardiography) reveal effects of 
hypermagnesemia but do not differentiate the 
cause.
• Though not described in critically ill 
veterinary patients, hypermagnesemia can 
cause prolonged PR intervals and QRS 
duration in humans.
  TREATMENT
• Management involves enhancing 
elimination from the body and symptomatic 
therapy.
• Discontinue all magnesium-containing 
medications and nutritional supplements.
• Saline diuresis and loop diuretics enhance 
renal clearance of magnesium.
• Fluid therapy with 0.9% NaCl provides 
fluid volume to address hypovolemia, 
hypotension, and azotemia.
• Patients with oliguria might require peritoneal 
dialysis to treat severe hypermagnesemia.
• Parenteral calcium supplementation directly 
antagonizes the effects of magnesium, 
reversing respiratory depression, cardiac 
arrhythmias, and hypotension; calcium also 
enhances magnesium excretion.
• Hypermagnesemia associated with 
combined angiotensin-converting enzyme 
inhibitors and spironolactone is rare, mild, 
and unlikely to be clinically significant.
• Physostigmine, an anticholinesterase, can 
be used to treat severe neurotoxic effects.
Patients with neurologic manifestations of 
hypermagnesemia might require intensive 
nursing care to prevent aspiration 
pneumonitis, pulmonary atelectasis, pressure necrosis (bed sores), and urine and fecal 
scalding.
ACTIVITY
Patient activity is dependent on underlying 
conditions and response to therapy.
DIET
Any magnesium supplementation should be 
Clients should be advised if preexisting 
conditions contributed to hypermagnesemia.
• Furosemide promotes renal excretion of 
magnesium by decreasing absorption of 
magnesium in the loop of Henle.
• Enteral and parenteral calcium adminis -
tration helps reverse clinical manifestations of 
hypermagnesemia and correct concurrent 
hypocalcemia; oral supplementation with any 
preparation can be given at a dosage of 
25–50 mg/kg/day; severe hypermagnesemia 
can be treated with 10% calcium gluconate: 
1–2 mL/kg (diluted 1 : 1 with saline) IV or 
SC q8h, administered slowly (may cause 
bradycardia).
Magnesium-containing compounds and 
fluids.
Monitor ECG during calcium infusion.
  FOLLOW-UP
• Serum magnesium and calcium 
• Renal function—azotemia and urine output.
• Continuous ECG if possible.
Magnesium supplementation should be 
approached cautiously in patients with renal 
• Severe hypermagnesemia and hypocalcemia 
can be fatal.• Hypermagnesemic dogs were 2.6 times less 
likely to survive their illness than patients 
with normal serum magnesium levels.
• Veterinary patients with iatrogenic overdose 
can have a good outcome with prompt 
recognition and supportive care.
• Increased ionized magnesium is rare and 
indicative of severe disease in noniatrogenic 
cases, particularly patients with acute renal 
disease, and can be associated with increased 
mortality.
Effects on the fetus are identical to effects on 
the dam.
SEE ALSO
Hypocalcemia
Bateman SW. Disorders of magnesium: 
magnesium deficit and excess. In: DiBartola 
SP , ed., Fluid, Electrolyte and Acid-Base 
Disorders in Small Animal Practice, 4th ed. 
Philadelphia, PA: Elsevier, 2011, pp. 
212–229.
Humphrey S, Kirby R, Rudloff E. 
Magnesium physiology and clinical therapy 
in veterinary critical care. J Vet Emerg Crit 
Care 2015, 25(2):210–225.
Jackson CB, Drobatz KJ. Iatrogenic 
magnesium overdose: 2 case reports. J Vet 
Emerg Crit Care 2004, 14(2):115–123.
Martin LG, Allen-Durrance AE. Magnesium 
and phosphate disorders. In: Silverstein DC 
and Hopper K, eds., Small Animal Critical 
Care Medicine, 2nd ed. Philadelphia, PA: 
Elsevier, 2015, pp. 283–284.
Nakayama T, Nakayama H, Hiyamoto M, 
Hamlin RL. Hemodynamic and 
electrocardiographic effects of magnesium 
sulfate in healthy dogs. J Vet Intern Med 
1999, 13:485–490.
Author  Timothy B. Hackett
Consulting Editor  Patty A. LathanHypermagnesemia  (continued)

Canine and Feline, Seventh Edition  689
HHypermetria and Dysmetria
  BASICS
• Dysmetria—incoordination of the limbs 
during voluntary movement because of an 
inability to judge the rate, range, and force of 
• Hypermetria—overreaching limb 
movements giving a characteristic goose-
stepping gait; the term dysmetria includes 
both hypo- and hypermetria.
• The cerebellum plays a central role in 
generating skilled movements and 
maintaining muscle tone and body posture; it 
does not initiate but coordinates and 
smoothes movements.
• Damage to the cerebellum results in 
inaccurate gauging of voluntary movements; 
motor strength is preserved; conscious 
proprioception is unaffected.
• Rarely, compression of the spinocerebellar 
tracts in spinal cord disorders can produce 
dysmetria; this is more likely to occur with 
dorsally located lesions.
GENETICS
• The hereditary ataxias are an important group 
of diseases in which cerebellar degenerations 
causes dysmetria and hypermetria in dogs.
• The majority of breed-related hereditary 
ataxias are autosomal recessive, highly 
penetrant traits.
• An X–linked hereditary ataxia has been 
described in pointers.
• Lysosomal storage diseases are genetic 
disorders, typically autosomal recessive in 
• Immune-mediated encephalitis likely has a 
hereditary component—the mode of 
inheritance has not been described but is 
complex.
The incidence and prevalence of this 
presenting problem have not been reported.
There are no data on geographic distribution.
SIGNS
Other signs of cerebellar disease that may be 
present include truncal sway, intention tremor, 
wide-based stance, head tilt, opsoclonus, 
spontaneous nystagmus, loss of menace 
response with normal vision, and anisocoria.
CAUSES
• Dogs—hypoplasia (inherited or secondary 
to infection with canine herpesvirus in the perinatal period); hereditary ataxia (cerebellar 
abiotrophy or cerebellar cortical degeneration); 
lysosomal storage diseases; canine distemper 
virus (CDV); protozoal infections ( Neospora 
caninum  is most common, Toxoplasma gondii  
is possible but rare); rickettsial infections 
(Ehrlichia canis  and Rocky Mountain spotted 
fever); Cryptococcus  and other fungal 
infections; granulomatous 
meningoencephalitis; meningoencephalitis of 
unknown etiology; steroid-responsive tremor 
syndrome; neoplasia; trauma; infarct; 
hemorrhage; metronidazole toxicity.
• Cats—hypoplasia secondary to in utero 
infection with feline panleukopenia virus; 
lysosomal storage diseases; feline infectious 
peritonitis (FIP), feline leukemia virus 
(FeLV), feline immunodeficiency virus (FIV; 
other encephalitides and to neoplasia); 
protozoal infections ( Toxoplasma gondii ); 
Cryptococcus  and other fungal infections; 
neoplasia; hemorrhage; trauma.
Spinal
• While there are many causes of spinal cord 
disease, centro-dorsally located cervical lesions 
are more likely to produce hypermetria.
• Dogs—subarachnoid diverticula; neoplasia; 
vertebral malformation (atlantoaxial 
subluxation); and calcinosis circumscripta.
• Hereditary ataxia reported in Gordon and 
Irish setters, Kerry blue terriers, Airedale 
terriers, Finnish harriers and hounds, 
Samoyeds, Bern running dogs, cocker 
spaniels, Cairn terriers, Australian kelpies, 
bull mastiffs, Italian spinones, the terrier 
group, Lagotto-Romangolos, Old English 
sheepdogs, Rhodesian ridgebacks, border and 
rough-coated collies, Brittany spaniels, 
beagles, and Scottish terriers.
• Cerebellar hypoplasia has been reported in 
chow chows, Irish setters, and wire fox terriers.
• Lysosomal storage diseases causing 
dysmetria have been reported in Siamese, 
Balinese, Persian, and domestic shorthair cats, 
and in English springer spaniels, American 
Staffordshire terriers, Portuguese water dogs, 
German shorthaired pointers, Australian silky 
terriers, schipperkes, English setters, border 
collies, salukis, Chihuahuas, Queensland blue 
heelers, dachshunds, Yugoslavian shepherds, 
and Tibetan terriers.
• Small-breed dogs, such as Maltese, 
Yorkshire and West Highland white terriers, 
miniature pinschers, and Chihuahuas, are 
predisposed to immune-mediated encephali-
tis, including meningoencephalitis of 
unknown etiology and steroid-responsive 
tremor syndrome.
• Metronidazole at dosages >60 mg/kg/day 
can induce cerebello-vestibular signs in dogs; 
signs are induced in some dogs at lower doses.• Vascular events, both thromboembolic and 
hemorrhagic, can cause cerebellar signs, 
typically due to thrombosis of the rostral 
cerebellar artery; disorders that cause a 
hypercoagulable state (such as hyperadreno-
corticism) or hypertension (such as hyperthy-
roidism in cats, or chronic renal disease) can 
predispose to stroke; hypothyroidism has also 
been associated with cerebellar stroke; 
thrombosis of the rostral cerebellar artery 
occurs in older dogs—an underlying cause is 
not always identified.
Spinal
• Giant-breed dogs are predisposed to 
vertebral malformation.
• Toy-breed dogs are predisposed to 
atlanto-axial instability.
• Young large-breed dogs are predisposed to 
subarachnoid diverticula and calcinosis 
circumscripta.
  DIAGNOSIS
Some dogs, especially small breeds, have a 
high-stepping gait in their thoracic limbs as a 
normal finding. If there are no other signs of 
cerebellar disease, establish with the owners 
whether a high-stepping thoracic limb gait is 
normal for the dog.
• CBC may reflect infectious/inflammatory 
disease.
• Storage products may be present in 
leukocytes in some lysosomal storage diseases.
• Acute and convalescent serologic titers—to 
diagnose rickettsial, protozoal, fungal, and 
viral diseases.
• Cerebrospinal fluid (CSF) antibody or 
antigen ( Cryptococcus ) titers—for some 
infections (e.g., Toxoplasma, Cryptococcus ), 
measure in addition to serologic titers.
rickettsial, bacterial, protozoal, fungal, and viral 
diseases; sensitive and specific if the infectious 
agent is present in the CSF or serum.
• Genetic tests available for hereditary ataxia 
in beagles, Finnish hounds, Italian spinones, 
Gordon setters, Old English sheepdogs, 
Lagotto-Romangolos, and the terrier group 
(Jack and Parson Russell terriers).
IMAGING
• Thoracic radiography—to identify 
metastatic disease in older patients.
• Abdominal ultrasonography—if intra-
abdominal neoplasia is suspected.
• Brain CT or MRI—to diagnose neoplasia, 
vascular disease, encephalitis, cerebellar 
atrophy due to hypoplasia or abiotrophy; 
MRI is the preferred modality for evaluating 
the caudal fossa.

690  Blackwell’s Five-Minute Veterinary Consult  
H• Survey spinal radiography—if spinal cord 
disease is suspected; may be helpful in 
identifying vertebral malformations and 
• Spinal MRI—noninvasive and informative 
about spinal cord parenchyma.
chorioretinitis (evidence of infectious/
inflammatory disease) and vascular lesions 
associated with vasculitis or hypertension.
• CSF—to diagnose encephalitis; storage 
products may be present in CSF leukocytes in 
some lysosomal storage diseases.
• Liver biopsy—may be helpful in diagnosing 
certain lysosomal storage diseases in animals 
with hepatomegaly.
• These will depend on the underlying 
• Hereditary ataxias are associated with loss 
of neurons of the cerebellar cortex, as well as 
axonal pathology and gliosis.
• Lyososomal storage diseases are associated 
with accumulation of storage product within 
neurons and glial cells; frequently the 
Purkinje neuron is most severely affected.
• Infectious encephalitis is associated with 
infiltration of the cerebellum with inflamma-
tory cells, and infectious organisms may be 
present (e.g., Neospora caninum ; Cryptococcal  
infections); meningitis and perivascular 
cuffing may be present and there is frequently 
multifocal involvement of the CNS; there is 
profound cerebellar atrophy associated with 
Neospora caninum  infections.
• Immune-mediated encephalitis is 
associated with infiltration of the CNS by 
inflammatory cells.  TREATMENT
• Severe and/or rapidly progressive clinical 
signs—hospitalization for diagnostic workup 
and treatment.
• Mild and slowly progressive clinical 
signs—outpatient, but diagnostic tests 
requiring anesthesia necessitate 
• Appropriate treatment of the underlying 
cause should be undertaken once a diagnosis 
has been established.
Severe intention tremors may make hand-
feeding and IV fluids necessary.
ACTIVITY
Patients should be restricted to areas and 
activities where they are unlikely to fall and 
injure themselves.
DIET
No change. Dogs may benefit from a raised 
feeding bowl or hand-feeding.
Surgical decompression of the spinal cord 
indicated for compressive myelopathies.
Discontinue metronidazole, regardless of the 
dose rate, to see if signs improve.  FOLLOW-UP
• Periodic repeat neurologic examinations.
• Additional monitoring will depend on the 
underlying cause (e.g., serial monitoring of 
blood pressure in hypertensive patients).
Fungal infections can be zoonotic.
pp. 368–390.
Urkasemsin G, Olby NJ. Canine hereditary 
ataxia. Vet Clin North Am Small Anim 
Pract 2014, 44:1075–1089.
Author  Natasha J. OlbyHypermetria and Dysmetria  (continued)

Canine and Feline, Seventh Edition  691
HHypernatremia
  BASICS
Serum sodium (Na+) concentration >158 mEq/L 
in dogs or >165 mEq/L in cats.
• Na+ is the most abundant cation in the 
extracellular fluid, so hypernatremia usually 
results in hyperosmolality.
• Hypernatremia can be caused by excessive 
free water loss, increased intake of Na+, or a 
combination of both.
• Common causes of hypernatremia include 
renal or gastrointestinal loss of water in excess 
of sodium loss and low water intake. Excessive 
Na+ ingestion is a rare cause.
• Nervous.
SIGNS
• Coma.
• Other findings depend on underlying 
cause.
• Severity of signs usually correlates to the 
degree of hypernatremia.
CAUSES
• Free water deficit (most common cause)—
low water intake (e.g., no access to water, 
adipsia, or hypodipsia); high urinary water 
loss; high insensible water loss (e.g., panting, 
hyperthermia).
◦ Urinary loss (e.g., diabetes insipidus, 
diabetes mellitus, osmotic diuresis, diuresis 
after acute urinary obstruction).
◦ Gastrointestinal sodium loss (e.g., 
administration of osmotic cathartic, 
vomiting, diarrhea).
◦ A wide variety of drugs interfere with 
renal capacity to concentrate urine, leading 
to water loss in excess of Na+; these drugs 
include lithium, demeclocycline, and 
amphotericin.
• Oral sodium ingestion (rare); IV 
administration of 0.9% or 7% NaCl; 
hyperaldosteronism (rarely hypernatremic); 
hyperadrenocorticism (mild).
  DIAGNOSIS
• Central diabetes insipidus (due to neoplasia 
or head trauma).• Alterations 
in thirst reaction pathway—rare.
• Salt ingestion—rare.
Results
Lipemia or hyperproteinemia ( >11 g/dL) can 
artifactually raise Na+ concentration when the 
flame photometry method is used.
Yes
• Consistent with underlying disease, if 
applicable.
• Diabetes insipidus—polyuria, hyposthenu-
ria, and low urinary Na+ concentration.
• Diabetes mellitus—hyperglycemia, 
IMAGING
CT scan or MRI in patients with diabetes 
  TREATMENT
• Fluid therapy and treatment of underlying 
disease.
• Water must be available at all times for 
patients with diabetes insipidus.
• If hypovolemia is present, replace volume 
with an isotonic crystalloid with a Na+ 
concentration within 10 mEq/L of the 
patient’s Na+ concentration (0.9% saline has a 
Na+ of 154 mEq/L, while lactated Ringer’s 
has 130 mEq/L and Normosol®-R has 
140 mEq/L). Volume replacement with this 
fluid may be continued as the free water 
deficit is replaced (below).
• Following volume resuscitation, administer 
hypotonic fluids (e.g., 5% dextrose in water 
or 5% dextrose with 0.45% saline) to reduce 
serum sodium by 0.5 mEq/h (12 mEq/L/
day); supplement with potassium and 
phosphate if needed.
• Free water deficit—Wt (kg) ×  
{[Na(presentation)]/ [Na(previous or normal)] – 1}: 
administer this amount to achieve an ideal 
decrease of 0.5 mEq/h (i.e., if the sodium is 
20 mEq above reference range, this should be 
administered over 40 hours).
• Formula to estimate how much each L of 
fluids will decrease the patient’s serum 
Na+—Δ in patient [Na+] = ([Na+] + [K+] in 1 L of solution – patient [Na+]) / (0.6 × Wt 
(kg) +1).
• If the patient has oral water intake, this 
should be calculated as part of the free water 
restoration.
cause cerebral edema. More rapid correction 
is only recommended if the hypernatremia is 
acute (<12 hours) or if the patient has 
neurologic abnormalities; correction should 
be slowed once signs abate.
• Cerebral edema is generally manifest as 
decreased mentation, and can be treated using 
hyperosmolar fluids (e.g., 7% NaCl, 
mannitol).
  FOLLOW-UP
• Acute setting—electrolytes, urine output, 
and bodyweight.
• Check sodium q4–6h initially and adjust 
fluid therapy as required to limit rapid 
changes.
• CNS thrombosis or hemorrhage.
• Hyperactivity.
• Serum sodium >180 mEq/L often 
associated with residual CNS damage.
None
SYNONYMS
None
SEE ALSO
• Diabetes Insipidus.
• Hyposthenuria.
DiBartola SP . Fluid, Electrolyte, and 
Acid-Base Disorders in Small Animal 
Practice, 4th ed. Philadelphia, PA: 
Rose BD. Clinical Physiology of Acid-Base 
and Electrolyte Disorders, 5th ed. New 
York: McGraw-Hill, 2001.

H
692  Blackwell’s Five-Minute Veterinary Consult  
HHyperosmolarity
  BASICS
• Osmolarity—mOsm/L: the number of 
solute particles per liter of solution.
• Osmolality—mOsm/kg: the number of 
solute particles per kilogram of solution.
• Hyperosmolarity—a high concentration of 
• Serum concentrations >310 mOsm/L in 
dogs and >330 mOsm/L in cats are 
considered hyperosmolar.
• Morbidity from hyperosmolarity is related 
more to rapid changes in osmolarity than to 
the actual amount of change.
• Serum sodium is responsible for most of the 
osmotically active particles that contribute to 
serum osmolarity; serum glucose and urea 
also contribute.
• Anything that causes free water loss increases 
concentrations of solutes in plasma or serum, 
thereby increasing serum osmolarity.
• Blood volume, hydration status, and anti­
diuretic hormone (ADH) are intimately involved 
in controlling extracellular fluid volume.
• Low circulating blood volume and low 
blood pressure stimulates carotid and aortic 
baroreceptors to cause ADH secretion.
• Hyperosmolarity affects the osmoreceptors 
in the hypothalamus and stimulates ADH 
secretion from the posterior pituitary; the 
hypothalamic thirst center is also stimulated 
and causes an increase in water consumption.
• Rapid increases in serum osmolarity cause 
water movement along its concentration 
gradient from intracellular to extracellular 
spaces, resulting in neuronal dehydration, cell 
shrinkage, and cell death; cerebral vessels may 
weaken and hemorrhage.
• Cardiovascular—hypovolemia, hypotension, 
decreased ventricular contractility.
• Nervous—excessive thirst may be the first 
sign of hyperosmolarity. CNS depression may 
lead to coma.
• Renal/urologic—low urine output unless 
kidneys are source of free water loss.
• Hypodipsia and hyperosmolarity have been 
reported in young female miniature 
SIGNS
• Primarily neurologic or behavioral.
• Severity is related more to how quickly 
hyperosmolarity occurs than to the absolute 
magnitude of change.
• Clinical signs most likely if serum osmolarity 
is >350 mOsm/L and severe if >375 mOsm/L.Historical Findings
Anorexia, lethargy, vomiting, weakness, 
disorientation, ataxia, seizures, and coma; 
polydipsia followed by hypodipsia.
• Normal, or abnormalities may reflect 
• In addition to historical findings, 
dehydration, tachycardia, hypotension, weak 
pulses, and fever may be detected.
CAUSES
Increased Solute Concentrations
Hypernatremia, hyperglycemia, severe 
azotemia, ethylene glycol toxicosis, salt 
poisoning, sodium phosphate enemas in cats 
and small dogs, mannitol, radiographic 
contrast solution, administration of ethanol, 
aspirin toxicosis, shock, and parenteral 
nutrition solutions.
Decreased Extracellular Fluid Volume
Dehydration—gastrointestinal loss, cutaneous 
loss, third ­space loss, low water consumption, 
polyuria without adequate compensatory 
polydipsia, excessive losses from panting.
• Medical conditions that predispose—renal 
failure, diabetes insipidus (DI), diabetes 
mellitus (DM), hyperadrenocorticism, 
hyperaldosteronism, and heat stroke.
• Therapeutic hyperosmolar solutions—
hypertonic saline, sodium bicarbonate, 
sodium phosphate enemas in cats and small 
dogs, mannitol, and parenteral nutrition 
solutions.
• High environmental temperatures, pain.
• Fever.
  DIAGNOSIS
• Primary CNS disease and neoplasia may be 
characterized by altered mentation, but serum 
osmolarity is usually normal.
• Physical evidence or history of injury 
usually helps to rule out CNS depression 
caused by cranial trauma.
• Perform a thorough physical examination 
to assess hydration status and obtain 
information regarding previous therapy that 
may have included sodium ­containing fluids 
or hyperosmolar solutions.
N/A
Results
N/A
YesCBC/BIOCHEMISTRY/URINALYSIS
High hematocrit, hemoglobin, and plasma 
proteins in dehydrated patients; serum 
electrolytes may also be increased.
• Osmolarity is generally measured in the 
laboratory using freezing point depression but 
can be estimated from serum chemistry 
results (assuming the absence of unmeasured 
osmoles) using the formula: 2(Na+ + K+) + 
glucose∕18 + BUN∕ 2.8 = mOsm∕L. Na+ and 
K+ concentrations are in mEq/L, glucose and 
blood urea nitrogen (BUN) concentrations 
are in mg/dL.
• Hyperosmolarity is an indication to 
evaluate serum sodium and glucose 
• Calculated osmolarity should not exceed 
measured osmolarity; if it does, consider 
laboratory error.
◦ If measured osmolarity exceeds calculated 
osmolarity, determine the osmolar gap.
◦ Osmolar gap = measured osmolarity – 
calculated osmolarity.
◦ High measured osmolarity and normal 
calculated osmolarity with a high osmolar 
gap indicate the presence of unmeasured 
solutes (not Na+, K+, glucose, BUN).
◦ High measured osmolarity and high 
calculated osmolarity with a normal 
osmolar gap usually indicate that the 
hyperosmolarity is caused by hyperglycemia 
or hypernatremia.
• Serum sodium concentration may be low in 
patients with severe hyperglycemia.
• Fasting hyperglycemia and glucosuria 
support a diagnosis of DM.
• Calcium oxalate monohydrate crystalluria 
suggests ethylene glycol toxicosis.
• High urine specific gravity (USG) rules 
out DI.
• Low USG, especially hyposthenuria, 
suggests DI.
• Urinary osmolarity lower than serum 
osmolarity suggests DI; concentrated urine 
rules out DI.
IMAGING
Renal ultrasonography may reveal bright 
hyperechoic kidneys in patients with ethylene 
glycol toxicosis.
TREATMENT
• Mild hyperosmolarity without clinical signs 
may not warrant specific treatment, but 
underlying disease(s) should be diagnosed and 
treated.
• Hospitalize patients with moderate to high 
osmolarity (>350 mOsm/L) and patients 
exhibiting clinical signs, and gradually lower 
serum osmolarity with IV fluids while a 
definitive diagnosis is pursued.
• Free water deficit can be calculated by 
the following formula: Free water deficit = 
0.4 × lean bodyweight (kg) × [(Plasma 
Na∕140) − 1].

Canine and Feline, Seventh Edition  693
HH• Administer 5% dextrose in water (D5W) or 
0.45% saline to slowly replace free water 
deficit.
• The goal is to not drop sodium more than 12 
mEq/L in an 24 ­hour period. For example, if 
the free water deficit is 1 L and serum sodium 
concentration is 180 mEq/L, to normalize 
serum sodium concentration (to 145 mEq/L), 
the sodium concentration should drop over 35 
hours (0.5 mEq/h). Thus, the 1 L of free water 
deficit should be given over 35 hours, or a rate 
of 28.5 mL/h (1000 mL/35h) if using D5W.  
Maintenance isotonic IV fluids should be 
administered concurrently.
• Initially, 0.9% saline may be used to restore 
vascular volume; once hemodynamically stable, 
D5W or 0.45% saline therapy may be initiated.
• If hyperosmolarity is acute (e.g. in patients 
with salt intoxication) and the duration is less 
than 6 ­8 hours, the free water deficit can be 
replaced more rapidly, through a combination 
of oral and IV water.
• If the patient is able to drink, free water 
deficit may be replaced orally; however, care 
must be taken to prevent excessive water 
• Intravenous free water replacement is best 
performed using D5W or 0.45% NaCl.
• Seizures can be controlled with 
benzodiazepines or phenobarbital.
Hypertonic saline and hyperosmolar 
solutions.PRECAUTIONS
• Initial volume replacement should use a 
fluid with a Na+ concentration closest to that 
of the patient.
• Rapid administration of hypotonic fluids 
(e.g., D5W and 0.45% saline) may cause 
cerebral edema and worsen neurologic signs 
due to acute fluid shifts in the brain.
Regular insulin 0.1 unit/kg IM/IV can be 
administered if a hyperglycemic crisis occurs 
secondary to parenteral nutrition administration.
  FOLLOW-UP
• Hydration status; avoid overhydration.
• Bladder size, urine output, serial bodyweight, 
and breathing patterns during IV fluid 
• Anuria, irregular breathing patterns, 
worsening depression, coma, or seizures are 
signs of deterioration.
Altered consciousness and abnormal behavior.
Hypernatremia and hyperglycemia.
None
N/ASEE ALSO
• Diabetes Mellitus with Hyperosmolar 
• D5W = 5% dextrose in water.
• DI = diabetes insipidus.
• DM =diabetes mellitus.
 Suggested Reding
DiBartola SP , ed. Fluid Therapy in Small 
Animal Practice. Philadelphia, PA: 
Saunders, 1992.
DiBartola SP , Green RA, Autran de Morais 
HS. Osmolality and osmolal gap. In: 
Willard MD, Tvedten H, T urnwald GH, 
eds., Small Animal Clinical Diagnosis by 
Laboratory Methods, 2nd ed. Philadelphia, 
PA: Saunders, 1994, pp. 106–107.
Goldcamp C, Schaer M. Hypernatremia in 
dogs. Compend Contin Educ Pract Vet 
2007, 29(3):148–152.
Schermerhorn T, Barr SC. Relationships 
between glucose, sodium, and effective 
osmolality in dogs and cats. J Vet Emerg 
Crit Care 2006, 16:19–24.
Melinda Fleming.(continued)  Hyperosmolarity

694  Blackwell’s Five-Minute Veterinary Consult  
HHyperparathyroidism
  BASICS
A pathologic, sustained, high, circulating 
concentration of parathyroid hormone (PTH).
• PTH is secreted by the parathyroid glands in 
response to changes in the concentration of 
ionized calcium in the serum, and causes an 
increase in serum calcium concentration 
through direct effects on bone and renal tubular 
calcium resorption and indirectly by vitamin 
D–dependent intestinal calcium absorption.
• Hyperparathyroidism can develop as a 
primary condition or be secondary to a 
disorder of calcium homeostasis; primary 
hyperparathyroidism is usually associated with 
benign adenoma of the parathyroid gland(s), 
although adenocarcinoma and hyperplasia are 
possible; secondary hyperparathyroidism can 
be caused by a deficiency of calcium and 
vitamin D associated with malnutrition or 
chronic renal disease.
GENETICS
• Autosomal dominant with possible 
age-dependent penetrance in the keeshond; 
genetic test available from Cornell.
• Secondary hyperparathyroidism can 
develop in association with hereditary 
nephropathy.
• Prevalence of primary form is unknown.
• More common in dogs than in cats.
• Common among causes of hypercalcemia, 
but less common than hypercalcemia of 
malignancy in dogs; more common in 
middle-aged to geriatric dogs.
• Chronic renal failure with secondary 
hyperparathyroidism is extremely common, 
more so in cats than in dogs.
• Nutritional secondary hyperparathyroidism 
is decreasing in prevalence as the public 
becomes more educated in pet nutrition.
Species
• Keeshond, but seen in almost any breed.
• Siamese and domestic shorthair cats.
• Cats—mean age 13 years; range: 8–20 years.
• Dogs—mean age 10 years; range: 4–17 years.
NoneSIGNS
• Most dogs and cats with primary hyper -
parathyroidism do not appear ill.
• Signs are usually mild and due to the effects 
of hypercalcemia, or lower urinary tract signs 
if urolithiasis is present.
• Stupor and coma.
• Often unremarkable.
• Parathyroid adenoma is not palpable in 
dogs but often is in cats.
• Nutritional secondary disease is sometimes 
associated with pathologic bone fractures and 
general poor body condition.
CAUSES
• Primary hyperparathyroidism—PTH-
secreting adenoma of the parathyroid gland; 
in most cases only one gland is adenomatous; 
malignant tumors of the parathyroid glands 
are uncommon and usually noninvasive.
• Renal secondary hyperparathyroidism—
renal calcium loss and reduced gut absorption 
of calcium due to deficiency in calcitriol 
production by the renal tubular cells.
• Nutritional secondary hyperparathyroidism—  
a nutritional deficiency of calcium and 
vitamin D.
• Primary hyperparathyroidism—unknown.
• Secondary hyperparathyroidism—renal 
tubular disease or calcium/vitamin D 
  DIAGNOSIS
• The differential list includes causes of 
• Lymphoma—common to cause hyper -
calcemia in dogs, rare to do so in cats.
• Anal sac apocrine gland adenocarcinoma— 
dogs.
• Other miscellaneous carcinomas—dogs and 
cats.
• Myeloproliferative disease—cats.
• Fibrosarcoma—cats.
• Vitamin D intoxication—cholecalciferol-
containing rodenticides, plant sources, human anti-psoriasis topical creams, and 
vitamin supplements.
• Granulomatous diseases.
• Idiopathic hypercalcemia in cats.
• High serum total and ionized calcium 
• Low or low-normal serum phosphorus 
concentration in primary hyperparathyroidism.
• Hyperphosphatemia in renal secondary 
hyperparathyroidism or hypervitaminosis D.
• Serum blood urea nitrogen (BUN) and 
creatinine concentrations are usually normal 
in patients with primary hyperparathyroidism, 
except those with hypercalcemia-induced renal 
failure.
• Serum ionized calcium determination is 
often normal (or low) in patients with 
chronic renal failure and high in patients 
hypercalcemia associated with malignancy.
• High serum intact PTH concentration is 
diagnostic for primary hyperparathyroidism in 
the absence of azotemia; a serum PTH 
concentration within the normal reference 
range in an animal with ionized hypercalcemia 
should be considered abnormal  and can signal 
parathyroid-dependent hypercalcemia.
• Measurement of PTH-related peptide 
(PTH-rp) may detect hyperparathyroidism 
related to neoplasia.
IMAGING
• Radiography can be useful to identify 
urolithiasis and occult neoplasia, as well as to 
assess renal morphology and bone density.
• Ultrasonography of the ventral cervical area 
sometimes reveals a parathyroid gland adenoma.
• Ultrasound of the abdomen can reveal 
lymphadenomegaly, urolithiasis, or renal 
morphologic abnormalities.
Surgical exploration of the ventral cervical area.
• Parathyroid adenoma is usually a solitary, 
small (=1 cm), round, light brown or reddish 
mass located in the proximity of the thyroid 
gland.
• Occasionally multiple adenomas are found.
• The histologic distinctions between 
adenomas, hyperplasia, and carcinomas of the 
parathyroid gland are often unclear.
  TREATMENT
• Primary hyperparathyroidism generally 
requires inpatient care and surgery.
• Nutritional or renal secondary hyper -
parathyroidism in noncritical patients can be 
managed on an outpatient basis.

Canine and Feline, Seventh Edition  695
HACTIVITY
No alterations recommended.
DIET
Calcium supplementation for secondary forms.
Explain signs referable to changes in calcium 
status, because hypocalcemia is a potential 
complication of parathyroidectomy.
• Surgery is the treatment of choice for 
primary hyperparathyroidism and is often 
important in establishing the diagnosis.
• Percutaneous ultrasound-guided heat 
ablation has been used successfully for 
treatment of parathyroid adenomas, and may 
be recommended if available.
• Percutaneous ultrasound-guided ethanol 
ablation has been reported to be less 
successful than surgery or heat ablation.
• Normal saline is the fluid of choice for 
treatment of hypercalcemia.
can be useful in treating hypercalcemia.
• No medical treatment exists for primary 
hyperparathyroidism per se.
• Renal secondary hyperparathyroidism is 
sometimes treated with calcitriol, but its use 
has not gained uniform acceptance.
• A new class of calcimimetic drugs is being 
used to treat renal secondary hyperpara -
thyroidism in human patients, but studies of 
these drugs in dogs and cats have not been 
reported and expense limits their use.
Do not use glucocorticoids until the diagnosis 
of lymphoma has been excluded; they can 
obfuscate the diagnosis.
Use furosemide only in patients with 
adequate hydration.
Pamidronate and other bisphosphonate drugs 
have been used to treat hypercalcemia of 
various causes in dogs and cats.  FOLLOW-UP
• Postoperative hypocalcemia is relatively 
common after treatment of primary 
hyperparathyroidism; recent studies have 
shown that preoperative ionized calcium and 
PTH concentrations are poor predictors of 
postsurgical hypocalcemia, so monitoring is 
essential in all cases.
• Postoperative hypocalcemia requires 
treatment with vitamin D (calcitriol is 
recommended) and calcium supplements (see 
treatment of hypoparathyroidism), and 
ionized calcium should be monitored to guide 
dosage adjustments; contradictory evidence 
exists with respect to preoperative admini -
stration of calcitriol.
• In patients with renal impairment, check 
serum concentrations of BUN and creatinine.
• Avoid breeding affected keeshonden.
is prevented by proper nutrition.
• Irreversible renal failure secondary to 
• Fractures due to decreased bone density 
with chronic hyperparathyroidism.
• Untreated primary hyperparathyroidism may 
progresses to end-stage kidney or neuro  muscular 
disease depending on severity; many dogs 
clinically seem to do well even with no treatment, 
provided urolithiasis does not develop.
• Prognosis for surgical treatment of 
parathyroid adenoma is excellent.
• Recurrence is seen in a small percentage 
of cases.
• In animals that develop postoperative 
hypoparathyroidism, the return of normal 
parathyroid function is unpredictable and can 
take weeks to months.
Calcium-containing urolithiasis.AGE-RELATED FACTORS
N/A
N/A
SEE ALSO
• PTH-rp = PTH-related peptide.
Dear JD, Kass PH, Della Maggiore AM, 
Feldman EC. Association of hypercalcemia 
before treatment with hypocalcemia after 
treatment in dogs with primary 
hyperparathyroidism. J Vet Intern Med 
2017, 31(2):349–354.
Feldman EC, Hoar B, Pollard R, Nelson RW. 
Pretreatment clinical and laboratory findings 
in dogs with primary hyperparathyroidism: 
210 cases (1987–2004). J Am Vet Med 
Assoc 2005, 227(5):756–761.
Milovancev M, Schmiedt CW. Preoperative 
factors associated with postoperative 
hypocalcemia in dogs with primary 
hyperparathyroidism that underwent 
parathyroidectomy: 62 cases (2004–2009). 
J Am Vet Med Assoc 2013, 
242(4):507–515.
Richter KP , Kallet AJ, Feldman EC, Brum 
DE. Primary hyperparathyroidism in cats: 
seven cases (1984–1989). J Am Vet Med 
Assoc 1991, 199(12):1767–1771.
Schaefer C, Goldstein RE. Canine primary 
hyperparathyroidism. Compend Contin 
Educ Vet 2009, 31(8):382–389.
available online(continued)  Hyperparathyroidism

696  Blackwell’s Five-Minute Veterinary Consult  
HHyperparathyroidism, Renal Secondary
  BASICS
OVERVIEW
• Syndrome characterized by a high 
parathyroid hormone (PTH) concentration 
secondary to chronic kidney disease (CKD); 
results from impaired renal excretion of 
phosphorus leading to hyperphosphatemia 
and ionized hypocalcemia, elevation of 
FGF-23, and suppression of renal calcitriol 
• In advanced CKD the diminished renal 
tubular mass produces less calcitriol. Calcitriol 
exerts negative feedback on PTH synthesis 
within the parathyroid gland. Low calcitriol, 
ionized hypocalcemia, and hyperphosphatemia 
result in increased PTH production and 
parathyroid gland hyperplasia.
• PTH may act as a uremic toxin, promoting 
nephrocalcinosis and progression of CKD.
Dog and cat; see Chronic Kidney Disease for 
age and breed predilections.
SIGNS
• Uremia due to underlying CKD.
• Renal osteodystrophy or “rubber jaw” most 
commonly occurs in young dogs with severe 
renal secondary hyperparathyroidism (RSHPT).
• Pain around the head or long bones.
• Any disease that causes CKD.
• Excess consumption of phosphorus.
  DIAGNOSIS
• Hypercalcemic nephropathy—kidney 
disease caused by ionized hypercalcemia; can 
be difficult to differentiate from longstanding 
RSHPT, in which hyperplasia of the 
parathyroid glands disrupts the normal 
feedback arc between PTH release and 
ionized calcium (tertiary 
hyperparathyroidism).
• Ionized serum calcium concentration is 
usually low or normal with RSHPT, but high 
with hypercalcemic nephropathy.
• Low serum PTH and PTH-related protein 
(PTHrP) high in animals with hypercalcemia 
of malignancy.
• Primary hyperparathyroidism—
characterized by hypercalcemia, normal or 
low serum phosphorus, and inappropriate 
PTH concentration; kidney function is 
initially normal but may become 
compromised later.
• Azotemia.• Hyperphosphatemia.
• Dilute urine.
• Total serum calcium does not reliably 
predict ionized calcium.
Definitive diagnosis and therapeutic 
monitoring of RSHPT require measurement 
of serum PTH concentration using validated 
assay.
IMAGING
Radiographs may reveal low bone density, loss 
of the lamina dura around the teeth, and soft 
tissue mineralization of the gastric mucosa or 
other tissues.
  TREATMENT
• See Chronic Kidney Disease for general 
treatment principles.
• Minimize hyperphosphatemia by feeding a 
low phosphorus diet formulated for kidney 
disease and intestinal phosphate binders in 
order to achieve IRIS phosphorus goals.
Intestinal Phosphate Binders
• If dietary management alone does not 
achieve the IRIS target serum phosphorus 
concentration, phosphorus binders can be 
used to further reduce serum phosphorus. 
Serum phosphorus targets based on the IRIS 
stages are stages 1 and 2: >2.7 to <4.6 mg/dL; 
Stage 3: >2.7 to <5.1 mg/dL; and Stage 4: 
>2.7 to <6.0 mg/dL.
• Aluminum hydroxide (60–90 mg/kg/day), 
calcium carbonate (90–150 mg/kg/day), 
calcium acetate (60–90 mg/kg/day), or 
lanthanum carbonate (60–90 mg/kg/
day)—dose to achieve target serum 
phosphorus concentration, but do not 
exceed max dosage. All must be given 
with meals.
• Calcium-containing phosphate binders 
should be avoided with calcitriol therapy as 
hypercalcemia may occur. Combine different 
phosphate binders to reduce the dosage of 
each and minimize the risk of hypercalcemia 
or aluminum toxicity.
Calcitriol
• Low-dose calcitriol (2.0–3.5 ng/kg PO 
q24h)—may use after serum phosphorus 
is controlled, should be administered on 
an empty stomach and before bedtime 
(no food for 6–8 hours after 
administration).• Maintain serum phosphorus concentration 
within the recommended IRIS target ranges 
before and during calcitriol therapy.
• Calcitriol therapy may result in hyper -
calcemia, especially if combined with a 
calcium-containing phosphate binder. 
Increased total calcium concentration may 
develop in patients with long-standing CKD, 
but is unrelated to calcitriol treatment. 
Ionized calcium concentration is normal or 
low in these patients.
• Do not use calcium-containing intestinal 
phosphate binders in patients with a calcium 
× phosphorus product >70. Use aluminum- 
or lanthanum-containing intestinal phosphate 
binders initially to correct hyperphosphatemia. 
Calcium-containing phosphate binders can be 
used once the serum phosphorus concentra-
tion is within the target range.
  FOLLOW-UP
• Initially and in unstable patients, serum 
concentrations of calcium, phosphorus, 
creatinine, and urea nitrogen—monitor 
weekly to monthly depending on therapy and 
the severity of CKD.
• Patients receiving calcitriol should be 
monitored for hypercalcemia and hyper -
phosphatemia weekly for 4 weeks, then every 
3–4 months.
• Serial evaluations of PTH concentration—
most treated with low-dose calcitriol achieve 
near-normal levels of PTH within 3 months; it 
may be necessary to increase the dose in those 
with severe parathyroid gland hyperplasia.
• If hypercalcemia develops discontinue 
calcitriol; calcium should normalize within 
5 days of discontinuation. Measurement of 
ionized calcium is recommended—animals with 
CKD may develop nonionized hyper  calcemia 
that is unrelated to calcitriol treatment.
Dietary phosphorus restriction may delay the 
onset of RSHPT.
Renal osteodystrophy and pathologic 
fractures (rare).
• Progression of the underlying CKD may be 
slowed by minimizing phosphorus retention 
and RSHPT.
• Long-term prognosis is guarded to poor for 
patients with CKD and RSHPT.

Canine and Feline, Seventh Edition  697
H  MISCELLANEOUS
Young animals can develop severe renal 
osteodystrophy; calcitriol may be beneficial.
• PTH = parathyroid hormone.• PTHrP = PTH-related protein.
• RSHPT = renal secondary 
Foster J. Update on mineral and bone disorders 
in chronic kidney disease. Vet Clin North Am 
Small Anim Pract 2016, 46(6):1131–1149.
Polzin D. Chronic kidney disease. In: 
Veterinary Internal Medicine, 7th ed. St. Louis, MO: Elsevier, 2009, pp. 
2036–2067.
Polzin DJ, Ross SJ, Osborne CA. Calcitriol 
therapy in chronic kidney disease. In: 
Bonagura J, ed., Current Veterinary 
Therapy XIV. Philadelphia, PA: Saunders, 
2008, pp. 892–895.
Consulting Editor  J.D. Foster(continued)  Hyperparathyroidism, Renal Secondary

698  Blackwell’s Five-Minute Veterinary Consult  
HHyperphosphatemia
  BASICS
• Serum total phosphorus >5.5 mg/dL 
(dogs).
• Serum total phosphorus >6 mg/dL (cats).
• Control of phosphorus is complex and is 
influenced by the actions of parathyroid 
hormone (PTH) and vitamin D and the 
interaction of these hormones with the 
parathyroid glands. The phosphatonin 
fibroblast growth factor-23 (FGF-23) also 
regulates phosphorus levels.
• High serum phosphorus results from 
excessive gastrointestinal absorption of 
phosphorus, excessive bone resorption of 
phosphorus, and/or reduced renal excretion 
of phosphorus.
• Metabolic.
• Renal.
GENETICS
N/A
N/A
N/A
• Any age, but commonly young, growing 
animals or older animals with renal 
SIGNS
• Depends on the underlying cause of 
• No specific signs directly attributable to 
• Acute hyperphosphatemia causes 
hypocalcemic tetany, seizures, or vascular 
collapse.
Chronic hyperphosphatemia causes calcifica-
tion of soft tissues, resulting in chronic renal 
failure and tumoral calcinosis.
CAUSES
• Reduced glomerular filtration rate.
• Renal hypoperfusion (e.g., hypovolemia, 
systolic cardiac disease).
• Postrenal urinary tract disease (e.g., 
obstruction, ruptured urinary bladder).
• Metabolic acidosis.
• Excessive bone resorption.
• Rhabdomyolysis or massive tissue trauma.
• Young growing dogs.• Hypoparathyroidism.
• Hypersomatotropism.
• Excessive gastrointestinal absorption of 
phosphorus.
• Osteolysis.
• Disuse osteoporosis.
• Osseous neoplasia.
• Phosphorus-containing enemas.
• Vitamin D toxicosis.
• Dietary supplementation.
• Nutritional secondary hyperparathyroidism.
• Use of phosphorus-containing enemas, 
especially in smaller animals.
• Massive tissue injury.
  DIAGNOSIS
• Hypoparathyroidism—also characterized by 
clinical signs of hypocalcemia such as seizures 
and tetany.
• Prerenal azotemia as a cause of hyperphos-
phatemia—associated with disease states that 
result in low cardiac output such as congestive 
heart failure, hypovolemia, hypoadreno -
corticism, and shock.
• Renal insufficiency, either acute or chronic 
renal failure—attended by azotemia and 
abnormal findings on urinalysis (low urinary 
specific gravity).
• Postrenal azotemia—associated with 
urinary obstruction or uroabdomen.
• Young, growing animals—can have serum 
phosphorus concentrations twice those of adults.
• Vitamin D intoxication—history of 
vitamin D supplementation or ingestion of 
rodenticides (e.g., Rampage® and D-CON®) 
or calcipotriene.
history of dietary calcium–phosphorus 
imbalance.
• Hyperthyroidism in cats—clinical signs of 
weight loss, polyphagia, and polydipsia and 
polyuria.
• Hypersomatotropism—attended by a 
history of progesterone administration in dogs 
and insulin-resistant diabetes mellitus in cats.
• Nonazotemia tumoral calcinosis—observed 
in human beings as an autosomal dominant 
disorder; rare cause of hyperphosphatemia 
associated with large bone lesions.
• Jasmine toxicity—history of plant ingestion.
• Rhabdomyolysis.
• T umor lysis syndrome.
• Spurious.
Intravenous potassium phosphate.Disorders That May Alter Laboratory 
Results
• Hemolysis, hyperbilirubinemia, and 
lipemia can falsely raise phosphorus 
• Collection in citrate, oxalate, or EDTA.
Yes
• Serum phosphorus >6 mg/dL.
• Low serum calcium in patients with 
primary hypoparathyroidism.
• High serum calcium in patients with 
vitamin D intoxication.
• Degree of azotemia and urine specific 
gravity help define level renal impairment.
molecule and two-site assay methods have the 
greatest specificity; high-normal or high 
concentrations with concurrent hyperphos-
phatemia suggest primary hyperparathy-
roidism; low concentrations with concurrent 
hypocalcemia and hyperphosphatemia suggest 
• Thyroxine concentrations—indicated in 
cats with hyperphosphatemia and clinical 
signs consistent with hyperthyroidism.
• Insulin-like growth factor 1 (IGF-1) 
concentrations—indicated in dogs or cats 
with unexplained hyperphosphatemia and 
clinical signs consistent with acromegaly; 
IGF-1 concentrations are elevated in animals 
with hypersomatotropism.
• Vitamin D assays are not readily available.
stimulation testing to confirm hypoadreno  - 
IMAGING
• Abdominal radiography to assess renal size 
and symmetry.
• Renal ultrasonography to detect soft tissue 
• Nuclear scintigraphy to rule out 
• Radiography of long bones to detect 
osteoporosis or neoplasia.
Renal biopsy.
Mineralization of soft tissues may be noted 
radiographically or histopathologically.
  TREATMENT
Inpatient, because of the deleterious effects of 
hyperphosphatemia and the need for fluid 
therapy; consider severe hyperphosphatemia a

Canine and Feline, Seventh Edition  699
Hmedical emergency. Long-term monitoring 
and management may be necessary.
Isotonic crystalloid fluids to increase 
glomerular filtration rate and promote 
phosphorus excretion.
ACTIVITY
N/A
DIET
Restrict dietary phosphorus.
Long-term monitoring and management may 
be necessary with phosphorus-restricted diets 
and/or oral phosphate binders.
N/A
Acute Hyperphosphatemia
• Dextrose (0.5–1 g/kg IV) and regular 
insulin (0.25–0.5 U/kg IV), to shift 
phosphorus intracellularly.
• Avoid phosphorus-containing fluids.
Chronic Hyperphosphatemia
Oral administration of phosphorus binders (e.g., 
aluminum hydroxide or aluminum carbonate, 
30–100 mg/kg/day PO, or calcium carbonate at 
90–150 mg/kg/day PO, both with meals).
N/A
Calcium carbonate should be avoided with 
N/A
The oral phosphate binders sevelamer 
hydrochloride and lanthanum carbonate may be used as oral phosphate binders, but 
relatively little information is available in the 
veterinary literature.
  FOLLOW-UP
• Serum calcium every 12 hours.
• Renal function tests—urine output must be 
monitored, particularly if oliguric renal failure 
is suspected, in which case urine output 
should be measured carefully; oliguria cannot 
be determined unless the patient is fully 
hydrated.
• Hydration status—indicators of over -
hydration include increased bodyweight, 
chemosis, increased central venous pressure, 
and edema (pulmonary or subcutaneous).
• Long-term serial monitoring of phosphorus 
is used to make dose adjustments in oral 
phosphate binders.
• Avoid ingestion of cholecalciferol 
rodenticides, calcipotriene, or Vitamin D 
• Avoid phosphate-containing enemas.
• Well-balanced veterinary diets prevent 
nutritional secondary hyperparathyroidism.
• Hypophosphatemia resulting in hemolysis.
• Soft tissue mineralization.
Depends on the underlying cause. Chronic 
kidney disease often causes chronic 
hyperphosphatemia and has a poor to 
guarded prognosis in dogs.
HypocalcemiaAGE-RELATED FACTORS
Mild elevations in phosphorus may be normal 
in growing animals.
N/A
N/A
SYNONYMS
N/A
SEE ALSO
• Hypoparathyroidism.
• FGF-23 = fibroblast growth factor-23.
• IGF-1 = insulin-like growth factor I.
Allen-Durrance AE. A quick reference on 
phosphorus. Vet Clin North Am Small 
Anim Pract 2017, 47:257–262.
Aurbach GD, Marx SJ, Spiegel AM. 
Parathyroid hormone, calcitonin, and the 
calciferols. In: Wilson JD, Foster DW, eds., 
Williams Textbook of Endocrinology, 7th 
ed. Philadelphia, PA: Saunders, 1985, pp. 
1208–1209.
Willard MD, Tvedten H, T urnwald GH. 
Clinical Diagnosis by Laboratory Methods. 
Philadelphia, PA: Saunders, 1989.
Deborah S. Greco.(continued)  Hyperphosphatemia

700  Blackwell’s Five-Minute Veterinary Consult  
HHypersomatotropism/Acromegaly in Cats
  BASICS
OVERVIEW
• Caused by excessive growth hormone (GH) 
secretion from the anterior pituitary by an 
adenoma or somatotroph hyperplasia.
• GH induces hepatic insulin-like growth 
factor-1 (IGF-1) secretion. The combination 
of increased GH and IGF-1 causes lipolysis, 
protein synthesis, impaired carbohydrate 
metabolism, and insulin resistance (IR).
• Prevalence in Europe ranges from 1 : 3 to 
1 : 5.5 diabetic cats.
• Median age—11 years (range: 9.5–13 years).
• Male : female ratio is 2 : 1.
SIGNS
• Clinical signs of diabetes mellitus (DM; 
e.g., polyuria, polydipsia, and polyphagia) 
occur from GH-induced IR. IR can be 
variable or persistent, which makes the DM 
difficult to control.
• Many (~40%) diabetics with hypersomato -
tropism (HST) lose weight due to poorly 
controlled DM; a small proportion (~17%) 
gain weight.
• Anabolic state—patients may present with 
polyphagia (without DM), or soft tissue 
growth resulting in upper airway obstruction, 
broad facial features, or clubbed feet.
• A small proportion (~2%) develop 
neurologic signs due to pituitary adenoma.
• GH-secreting pituitary adenoma or 
somatotroph hyperplasia.
• In dogs, but not cats, progestins can result 
in increased GH concentration.
  DIAGNOSIS
• Uncomplicated DM.
• Pituitary-dependent hyperadrenocorticism.
• Causes of polyphagia such as exocrine 
pancreatic insufficiency, gastrointestinal 
inflammatory diseases, hyperthyroidism, and 
inflammatory liver diseases. Cats with HST 
and polyphagia but without DM typically 
gain weight, unlike other differentials.
• Consistent with DM.
• Diabetic ketoacidosis uncommon.
• Serum IGF-1 concentration using validated 
assays is test of choice.
◦ Positive predictive value of IGF-1 
>1000 ng/mL (131 nmol/L) of 95%.◦ Roughly one-third of cats with HST have 
a low IGF-1 at diagnosis, which increases to 
>1000 ng/mL after insulin therapy.
◦ IGF-1 concentrations between 700 and 
1000 ng/mL (92–131 nmol/L) is a “gray” 
zone—many non-HST diabetic cats are in 
this range.
• There is no commercially available GH 
assay.
IMAGING
• Abdominal ultrasound might identify 
organomegaly.
• Contrast-enhanced CT can assess pituitary 
size.
• Echocardiographic findings—increased left 
ventricular wall thickness, left atrial 
enlargement, aortic insufficiency.
  TREATMENT
Surgery
Hypophysectomy most consistently normal-
izes IGF-1 concentration (80% of cases) and 
results in highest diabetic remission rates 
(50% achieve long-term remission).
• Somatostatins (SSTs) are primary negative 
regulatory hormones of GH secretion.
• Pasireotide is an SST analogue. Short-
acting pasireotide (0.03 mg/kg SC q12h) 
decreased IGF-1 in 12 cats after 3 days of 
treatment, while long-acting pasireotide 
(8 mg/kg SC monthly) resulted in 
normalization of IGF-1 in 2/8 cats; all cats 
experienced increased insulin sensitivity and 
3/8 cats achieved diabetic remission.
• Octreotide is an SST analogue with a 
different binding profile that temporarily 
decreases GH without improvement in 
clinical control of HST or DM.
• Dopamine receptor 2 inhibits GH 
secretion. Cabergoline, a dopamine receptor 
2 agonist, decreases IGF-1 and increases 
insulin sensitivity in some cats with HST.
Radiotherapy
Fractionated radiotherapy improves neuro-
logic signs and may improve diabetic control. 
Stereotactic radiotherapy might be more 
favorable as improved diabetic control and 
diabetic remission is more likely.
Palliative Treatment
• Maximizing diabetic control (e.g. with 
insulin and diet) is recommended but may be 
challenging.
• Comorbidities (e.g., osteoarthritis, cardiac 
disease) should be managed.
• Controlling polyphagia in some cats with 
HST is challenging. Despite lack of endocrine 
improvement after cabergoline, many owners 
reported normalization of appetite.  MEDICATIONS
See Medical Management.
  FOLLOW-UP
• Depends on treatment modality.
• Survival varies from months to years; most 
euthanized due to poor quality of life or 
causes unrelated to HST.
• Diabetic control should be monitored as for 
an uncomplicated diabetic. A small 
proportion of cats gain weight despite poor 
diabetic control and have persistent 
polyphagia despite good diabetic control.
• GH = growth hormone.
• HST = hypersomatotropism.
• IGF-1 = insulin like growth factor-1.
• IR = insulin resistance.
• SST = somatostatin.
Berg RI, Nelson RW, Feldman EC, et al. 
Serum insulin-like growth factor-I 
concentration in cats with diabetes mellitus 
and acromegaly. J Vet Intern Med 2007, 
21(5):892–898.
Gostelow R, Scudder C, Keyte S, et al. 
Pasireotide long-acting release treatment for 
diabetic cats with underlying 
hypersomatotropism. J Vet Int Med 2017, 
31(2):355–364.
Wormhoudt TL, Boss M-K, Lunn K, et al. 
Stereotactic radiation therapy for the 
treatment of functional pituitary adenomas 
associated with feline acromegaly. J Vet Int 
Med 2018, 32(4):1383–1389.
Author  Christopher J. Scudder
of Deborah S. Greco and David Church.

Canine and Feline, Seventh Edition  701
HHypertension, Portal
  BASICS
Portal pressure >13 cm H2O (10 mmHg).
• Causes—increased portal blood flow 
(arterialized system), increased resistance to 
portal blood flow, or combination.
• Increased portal flow—arterialization of 
portal circulation occurs in arteriovenous (AV) 
malformation or subsequent to increased 
hepatic resistance causing retrograde blood flow 
into valveless splanchnic portal circulation.
• Hepatofugal—portal splanchnic circulation 
away from liver.
Increased Resistance Relative to Liver
• Prehepatic—abdominal portion of portal 
vein.
• Hepatic—within liver.
• Posthepatic—cranial to liver: terminal 
hepatic veins, vena cava, heart, pericardium.
Intrahepatic Increase in Resistance
• Presinusoidal—within portal tract.
• Sinusoidal—within sinusoid or space of Disse.
• Postsinusoidal—hepatic venular outflow 
tract causing sinusoidal occlusion or Budd 
Chiari syndrome.
• Consequences—development of multiple 
acquired portosystemic shunts (APSS), 
abdominal effusion due to increased lymph 
formation, predisposition to hepatic 
• Acquired portosystemic shunts (APSS)—
develop within 1–2 months of acquired portal 
hypertension (PH).
Effusion Protein Content
• Hepatic causes—pure transudate reflects 
concurrent PH and hypoalbuminemia 
(protein <1.5 g/dL).
• Posthepatic causes—modified transudate 
(protein >2.5 g/dL).
• Prehepatic causes—pure or modified 
transudate, low cellularity.
• Hepatobiliary disorders—obstructed blood 
flow in any zone or diffusely across sinusoids 
causes intrahepatic PH, splanchnic PH, ± 
passive splenic congestion (splenomegaly).
• Posthepatic disorders—hepatic passive 
congestion, hepatomegaly, variable PH; APSS 
usually absent .
• Prehepatic disorders—cause splanchnic PH, 
splenic congestion, APSS; portal venous 
thrombi, stenosis, stricture, entrapment in 
porta hepatis (e.g., pancreatitis, neoplasia), 
mass compression (pancreatic inflammation; 
• Nervous—HE due to APSS.
• Cardiovascular—APSS and ascites may 
develop with vena caval/hepatic vein obstruction (at level of diaphragm), but not  
with congestive heart failure or pericardial 
tamponade.
• Portal thrombi—caused by gastrointestinal 
(GI) inflammation/necrosis and splanchnic 
vasculitis, neoplasia, disseminated intravascu-
lar coagulation, loss of anticoagulants, 
accelerated thrombosis.
• GI—splanchnic hypertension can provoke 
enteric edema, increased gut wall permeability 
provoking transmural bacterial translocation 
(endotoxemia, bacteremia), hypertensive 
enteric vasculopathy (enteric bleeding, 
ulceration), diapedesis blood loss, protein 
malassimilation.
GENETICS
• Vascular malformations causing portal 
atresia (intrahepatic, prehepatic) are 
congenital and represent severe phenotype of 
polygenic portal venous malformations in 
small-breed dogs.
• Ductal plate malformation (DPM)—congenital 
hepatic fibrosis (CHF) phenotype causes APSS; 
occurs in numerous dog breeds and Persian-
related cats; increased frequency in boxers.
• Noncirrhotic PH—adult-onset diminution 
of tertiary portal branches, affects individual 
dogs of many breeds, described in Doberman 
pinschers (rare).
• Acquired sinusoidal PH due to necroin-
flammatory liver injury—immune-mediated 
chronic hepatitis (anecdotal in some breeds).
• Copper associated hepatopathy—
Bedlington terrier COMMD1  mutation, 
predisposition for copper associated hepatop-
athy in Labrador retrievers, Dalmatian, 
Doberman pinscher, and numerous other 
dogs may reflect pharmacogenetic breed 
differences in copper transporters.
Species
Dog > cat.
Familial hepatic vascular disorders—
Doberman pinschers (noncirrhotic PH); 
Saint Bernard (AV malformation); cocker 
spaniel hepatopathy; copper associated 
hepatopathy: Bedlington terriers, Doberman 
pinschers, Labrador retriever, others; DPM 
with CHF phenotype: boxers predisposed, 
any large or small dog breed, cats.
• Juveniles—inherited or congenital 
disorders; vena caval and cardiac 
• Young dogs and cats <1.5 years of age—con -
genital hepatic vascular malformations with 
portal venous atresia: may be more common in 
Yorkshire terriers, Maltese, pugs, cats.
• Juvenile and young adult dogs and cats—
DPM with CHF phenotype.
• Young dogs and cats—hepatic AV 
malformations, onset of signs <1.5 years of age.• Middle-aged and older animals—acquired 
hepatobiliary disorders and portal thrombi.
SIGNS
• Depend on site, degree, rate of onset of PH, 
and causal factors.
• Acquired disorders—slowly progressive, 
chronic in onset.
• Portal thromboembolism may acutely 
appear but remain unnoticed until APSS 
form; vague GI signs at occurrence including 
bloody diarrhea, ileus, abdominal pain, 
lethargy, inappetence.
• Abdominal distention—ascites.
• HE—secondary to APSS.
• Cardiac disorders or pericardial restriction—
cough; exercise intolerance; dyspnea, jugular 
pulse, weak femoral pulses or pulsus alternans, 
reduced heart sounds on auscultation.
• Hepatomegaly—posthepatic causes only.
• Splenomegaly—reflects splanchnic 
congestion or venous thrombi, inconsistent.
• Jugular vein distention—posthepatic 
cardiac or pericardial causes.
• Muffled heart sounds—pericardial or 
• Cardiac arrhythmias or murmur—cardiac 
disease.
• Pulmonary “crackles” (edema)—cardiac or 
pericardial causes.
• Confusion, stupor, coma, blindness, other 
neurobehavioral abnormalities—HE.
• Jaundice—hepatic causes.
• Hepatic bruit (hepatic AV malformation).
• Signs consequent to surgical ligation of 
portosystemic venous anomaly (PSVA).
CAUSES
Prehepatic
• Portal vein thrombosis, stenosis, or 
• Portal vein compression—large lymph nodes; 
neoplasia, granuloma; abscess; pancreatitis, 
entrapment in diaphragmatic hernia.
• Postoperative complication of PSVA 
ligation.
• Congenital portal vein atresia.
Intrahepatic
• Hepatic fibrosis/cirrhosis.
• Chronic inflammatory liver disease.
• Chronic extrahepatic bile duct obstruction 
(EHBDO) >6 weeks.
• DPM with CHF phenotype.
• Hepatic neoplasia—porta hepatis location.
• Liver entrapment—in diaphragmatic hernia.
• Sinusoidal occlusion syndrome.
• Veno-occlusive disease (zone 3 lesion).
• Noncirrhotic portal hypertension.
• Portal vein atresia (intra- or extrahepatic).
• Hepatic AV malformation.

702  Blackwell’s Five-Minute Veterinary Consult  
HPosthepatic
• Right-sided congestive heart failure.
• Pericardial tamponade.
• Pericarditis—restrictive or constrictive.
• Cardiac neoplasia.
• Cor triatriatum dexter.
• Pulmonary thromboemboli (TE).
• Disorders affecting supradiaphragmatic 
caudal vena cava— thrombosis; congenital 
kink or web; heartworm vena cava syndrome; 
occlusion by neoplasia; entrapment in 
diaphragmatic hernia; trauma.
• Budd Chiari syndrome.
  DIAGNOSIS
• Physicochemical analysis of abdominal 
effusion—helps narrow diagnoses.
• Pure transudate—hypoalbuminemia 
secondary to protein-losing enteropathy 
(PLE), protein-losing nephropathy (PLN), 
liver failure.
• Modified transudate with normal or low 
albumin—PLE, PLN, liver failure (chronic 
effusion), neoplasia, splanchnic TE, liver 
(visceral) entrapment in diaphragmatic hernia.
• Modified transudate with large liver and 
jugular distention—cardiac or pericardial 
abnormalities; heartworm; right atrial tumor.
• Modified transudate with large liver 
without jugular distention, muffled heart, or 
pulmonary edema—kinked vena cava; Budd 
Chiari–like or sinusoidal occlusion syndrome.
• HE— liver fibrosis; cirrhosis; CHF; hepatic 
AV malformation; any cause of APSS.
• Jaundice—chronic hepatitis, cholangitis; 
EHBDO; infiltrative hepatic neoplasm.
• Bloody diarrhea, abdominal pain, ileus, signs 
of endotoxemia—acute splanchnic portal TE.
• CBC—schistocytes with TE; red blood cell 
microcytosis with PSVA or APSS; icteric 
plasma with liver disease or microangiopathic 
shearing anemia.
• Biochemistry—liver disease associated with 
variable liver enzymes, low blood urea 
nitrogen, creatinine, cholesterol, and/or 
glucose concentrations, hyperbilirubinemia, 
coagulation abnormalities; posthepatic 
disorders associated with high liver enzymes, 
± azotemia, normal plasma color.
with APSS; may note granular casts with TE 
affecting renal perfusion; may note proteinu-
ria with heartworm disease.
• Total serum bile acids (TSBA)—variable 
fasting and high 2h postprandial concentra-
tions with APSS or hepatobiliary disease; shunting pattern (normal fasting and 
markedly high postprandial values) common.
• Blood ammonia—hyperammonemia with 
APSS or inferred by finding ammonium 
biurate crystalluria; less reliable compared to 
TSBA.
• Physicochemical characterization of 
abdominal effusion—high serum : effusion 
albumin ratio ( >1.1) consistent with PH.
IMAGING
• Thoracic radiography—may reveal cause of 
posthepatic PH.
• Abdominal radiography—may reveal 
effusion, splenomegaly, hepatomegaly; 
microhepatica in most hepatic disorders and 
portal atresia causing APSS.
ABDOMINAL US
• Identify abnormalities involving abdomi -
nal or extrahepatic portal vein—atresia, 
stricture, thrombi, occlusive lesions in porta 
hepatis.
• Identify lobe(s) containing AV 
• Inspect splanchnic circulation using 
Doppler color flow; document hepatofugal 
circulation, identify portal thrombi, APSS, 
PSVA.
• Evaluate echogenicity of nonhepatic viscera, 
identify lymphadenomegaly, mass lesions, 
• Estimate hepatic venous distention—intra-
hepatic and supradiaphragmatic segments.
Detects congenital and acquired cardiac 
and pericardial disorders, neoplasia, 
thrombi, heartworms, pleural effusion, 
malformed or thrombosed vena cava, 
Angiography and Nuclear Imaging
• Colorectal or splenoportal scintigraphy—
confirms portosystemic shunting but not 
anatomic details.
• Radiographic angiography—celiac trunk 
and hepatic artery contrast studies confirm 
hepatic AV malformation; nonselective or 
selective studies: congenital cardiac disease, 
TE, hepatic vein disorders, AV 
• Portovenography—confirms APSS.
• Multisector CT—displays arterial and 
venous phases.
• ECG and central venous pressure—with 
cardiac disease, cranial mediastinal 
obstructions.
• Liver biopsy—required for diagnosis of 
hepatobiliary disorders.
• Portal pressure—may be measured during 
laparotomy but not recommended; PH 
adequately confirmed with imaging studies 
and on gross inspection.  TREATMENT
Inpatient—for severe HE, amelioration of 
tense ascites by therapeutic abdominocentesis, 
supportive care for acute TE.
• Fluid therapy—restrict sodium concentra-
tion (avoid 0.9% NaCl); avoid iatrogenic 
pulmonary edema during fluid therapy 
(caution : if hypoalbuminemia, monitor 
respiration rate/effort).
• Monitor bodyweight and condition, girth 
circumference, plasma proteins, packed cell 
volume—assess hydration status, volume of 
abdominal effusion, IV fluid tolerance.
• Low oncotic pressure—may require plasma 
or colloid administration (plasma preferred 
for liver patient); Voluven® or VetStarch® (6%; 
130 MW/0.4 molar substitution) 10–20 mL/
kg/day IV CRI) may be necessary for acute 
adjustments; avoid hetastarch as can reduce 
platelet function.
• Glucose supplementation—with hepatic 
dysfunction and hypoglycemia; 2.5–5.0% 
dextrose with half-strength polyionic fluids 
initially; avoid hyperglycemia.
Mobilization of Ascites
• Abdominal effusion —sequentially assess: 
bodyweight, girth, body condition score; 
initially exercise restrict; enforce dietary 
sodium restriction.
• Conventional diuretics —combine furosem-
ide and spironolactone; furosemide 
(0.5–2 mg/kg PO q12–24h) and spironolac-
tone (0.5–2 mg/kg PO q12h, use single 
doubled dose for loading one time): dose 
titrations based on response q4 days; adjust 
using incremental 25–50% dose increase; 
serum : effusion albumin ratio ( >1.1) may 
predict response to diuretics.
• Vasopressin V2 antagonists  (aquaretics) may 
assist with management of diuretic-resistant 
congestive heart failure; human dose in 
cirrhosis 7.5 mg/day; metabolized exclusively 
in liver primarily by cytochrome P450; dose 
undetermined in dogs with liver disease.
• T elmisartan— angiotensin receptor blocker is 
alternative diuretic worthy of consideration; 
administration PO at 1.0 mg/kg/day signifi -
cantly increased urine volume and sodium 
excretion in healthy dogs in one study.
• Taper diuretic dose after initial positive 
response; individualize chronic treatment to 
response; may be used intermittently for 
recurring ascites.
• Avoid dehydration, can lead to HE.
• Avoid hypokalemia, can provoke HE.
• If ascites due to right-sided congestive heart 
failure, treat accordingly.Hypertension, Portal  (continued)

Canine and Feline, Seventh Edition  703
H• Diuretic-resistant ascites —large-volume 
(therapeutic) abdominocentesis if ascites 
resistant to medical intervention or compro-
mises food intake, ventilation, or sleep: 
requires aseptic technique, fluid removal over 
45–90 min, concurrently provide polyionic 
fluids in moderation with colloids to reduce 
risk for postcentesis hypotension and acute 
renal failure (ARF); repeated large-volume 
fluid removal may result in hypovolemia, 
hypoproteinemia, electrolyte depletion; 
iatrogenic infection; postcentesis hypov-
olemia/hypoperfusion syndrome, ARF; 
general rule in humans: provide 4–8 g 
albumin per L of ascites removed (consider 
colloids, discussed above).
• If ascites fails to mobilize, consider measur -
ing urine sodium output vs. sodium intake 
(dietary) to determine whether intake requires 
restriction or diuretics upward titration; urine 
output should be measured over min 12h.
ACTIVITY
Depends on cause—restrict activity if ascites.
DIET
• Ascites—restrict dietary sodium 
<100 mg/100 kcal.
• If HE—restrict dietary protein; caution : 
only do so if nitrogen intolerance suspected.
Inform client definitive diagnosis requires 
logical diagnostic strategies and no prediction 
for cure or chronic amelioration until 
diagnosis definitive.
• Ligation of APSS or vena caval banding 
strongly contraindicated.
• If acute symptomatic PH after surgical 
ligation of PSVA—ligature removal imperative.
• Embolectomy of thrombi not recommended; 
emboli may recanalize with supportive care; clot 
dissolution (streptokinase, tissue plasminogen 
activator) complicated, expensive, requires ICU 
hospitalization and monitoring, warrants grave 
• Low molecular weight heparin—see 
Coagulopathy of Liver Disease.
• Correction of chronic diaphragmatic 
hernia—release of entrapped viscera may 
provoke perioperative/postoperative 
endotoxemia, hypotension, shock, ARF .
• Surgical correction and cure of cor 
triatriatum and kinked vena cava possible.• Pericardectomy—pericardial restriction or 
tamponade; thoracoscopic procedure least 
invasive, with lowest mortality and best 
outcome.
• Removal of tumor or fibrous adhesions 
causing hepatic vein occlusion may be 
difficult.
• Removal (lobectomy) or embolization 
(acrylamide) of hepatic AV malformation may 
not be curative as microscopic intrahepatic AV 
shunting usually continues PH and APSS.
T reatment of abdominal effusion—sodium 
restriction (see Diet); combined diuretic 
therapy (spironolactone and furosemide), 
consider tolvaptan or telmisartan (see above), 
use large-volume paracentesis sparingly.
• Avoid drugs relying on first-pass hepatic 
extraction, biotransformation, or hepatic 
elimination; if not possible, adjust dosage 
based on available information.
• Reduce dose of highly protein-bound drugs 
if patient hypoalbuminemic.
drugs—may provoke ARF , sodium retention, 
and enteric bleeding that may augment HE.
  FOLLOW-UP
• Sequentially monitor bodyweight, 
condition, abdominal girth.
• Sequentially assess hydration, electrolytes, 
acid-base, BP as necessary.
• Monitor albumin and glucose—with liver 
disease or APSS.
• Monitor lung sounds, pulse oximetry, 
ventilatory effort—in cardiovascular 
• Thrombosis.
• Acute renal failure.  MISCELLANEOUS
• Chronic liver disease.
• Numerous disorders may cause prehepatic 
or posthepatic portal hypertension.
Affects uterine perfusion and likely leads to 
abortion or stillbirths.
SEE ALSO
• Ascites.
• Portosystemic Shunt, Acquired.
• ARF = acute renal failure.
• APSS = acquired portosystemic shunt(s).
• PSVA = portosystemic venous anomaly.
Bunch SE, Johnson SE, Cullen JM. 
Idiopathic noncirrhotic portal hypertension 
in dogs: 33 cases (1982–1998). J Am Vet 
Med Assoc 2000, 218:392–399.
Buob S, Johnston AN, Webster CR. Portal 
hypertension: pathophysiology, diagnosis, 
and treatment. J Vet Intern Med 2011, 
25:169–186.
Acknowledgment  The author/book editors 
acknowledge the prior contribution of Sharon 
A. Center.(continued)  Hypertension, Portal

704  Blackwell’s Five-Minute Veterinary Consult  
HHypertension, Pulmonary
  BASICS
Peak systolic pulmonary artery (PA) pressure 
>35 mmHg and/or peak diastolic PA pressure 
>15 mmHg.
• Causes of elevated PA pressure: ◦ PA 
vasoconstriction. ◦ PA obstruction. ◦ High left 
atrial (LA) pressure. ◦ Excessive pulmonary 
blood flow. • As a result of pulmonary hyper­
tension (PH) right heart pressures increase to 
maintain pulmonary blood flow. ◦ May result 
in dysfunction of right ventricle RV and 
decreased pulmonary blood flow, which 
interferes with left heart filling and can lead to 
reduced cardiac output. ◦ High right heart 
pressures can cause venous congestion, tricuspid 
regurgitation (TR), and right ­sided CHF .
• Cardiovascular. • Respiratory. 
• Hepatobiliary (if right ­sided CHF).
GENETICS
• No specific genetic basis found. • Causes of 
primary disease (congenital heart disease 
[CHD], left heart disease, pulmonary disease) 
may have a genetic basis.
Unknown; higher prevalence in heartworm ­
endemic areas and high altitudes.
Species
• Possibly based on underlying cause of PH. 
• Increased incidence suggested in terrier breeds.
Increased incidence reported in females.
SIGNS
Signs due to hypoxia and cardiac dysfunction.
• Exercise intolerance. • Dyspnea/tachypnea. 
• Coughing/hemoptysis. • Syncope. 
• Abdominal distention. • Weight loss. 
• Lethargy. • Sudden death.
• Dyspnea/tachypnea. • Coughing/
hemoptysis. • Loud and/or split second heart 
sound. • Pulmonary crackles and/or 
increased bronchovesicular sounds. 
• Cyanosis. • Heart murmur. • Abdominal 
distention. • Jugular distention. 
• Subcutaneous edema. • Weight loss.
CAUSES
Primary/Idiopathic/Familial PH
• Congenital disorders of the pulmonary 
vasculature identified in humans. • Abnormalities in endothelial derived 
vasodilator/vasoconstrictor substances 
result in vascular obstruction and 
vasoconstriction. • Not reported in 
• Vascular obstruction —resulting from 
pulmonary lesions (e.g., fibrosis, neoplasia), 
vascular hypertrophy/inflammation. 
• Vasoconstriction —secondary to hypoxia and 
acidemia. • Causes —pneumonia (bacterial, 
viral, fungal, parasitic); chronic bronchitis; 
pulmonary fibrosis; eosinophilic bronchitis; 
pulmonary neoplasia; acute respiratory 
distress syndrome.
Pulmonary Thromboembolism (PTE)
• Vascular obstruction —secondary to 
thrombus. • Vasoconstriction —secondary to 
hypoxia and vasoconstrictive substances 
released from the thrombus. • Causes —
hyperadrenocorticism; protein ­losing 
nephropathy/enteropathy; sepsis; immune ­
mediated hemolytic anemia; neoplasia; 
pancreatitis; endocarditis; disseminated 
intravascular coagulation; primary cardiac 
disease (typically right ­sided).
Heartworm Disease (HWD)
• Vascular obstruction —vascular hypertrophy, 
inflammation, thromboembolism, and 
presence of heartworms. • Vasoconstriction —
secondary to hypoxia/thrombi.
Left-to-Right-Shunting CHD
• Excessive pulmonary blood flow —results in 
damage to pulmonary vasculature. 
• Vasoconstriction /vascular obstruction —due to 
vascular damage and hypertrophy. • Causes—
patent ductus arteriosus; ventricular septal 
defect; atrial septal defect; atrioventricular 
septal defect.
Left Heart Disease
• High LA pressure —results in pulmonary 
venous hypertension. • Vasoconstriction/
vascular obstruction —result of elevated 
pressure and vascular hypertrophy. • Causes—
mitral regurgitation; cardiomyopathy (dilated, 
hypertrophic, restrictive, unclassified); mitral 
stenosis; congenital pulmonary venous 
obstruction; LA tumors.
Extrapulmonary Causes of Chronic 
Hypoxia
• Vasoconstriction and secondary vascular 
hypertrophy —due to environmental/
extrapulmonary factors that result in 
hypoxia and acidemia. • Causes—
hypoventilation (Pickwickian syndrome, 
neuromuscular disorders); high altitude 
disease.
• Cardiac and pulmonary disease. • HWD. 
• Diseases causing hypercoagulability.  
• Obesity. • High altitude.  DIAGNOSIS
• Left­sided CHF*. • T racheal collapse. 
• Right ­sided CHF*. • Primary pulmonary 
disease*. • HWD*. • Pneumothorax. 
• Pleural effusion (pyothorax, chylothorax, 
hemothorax, hydrothorax). • Laryngeal 
disease. * = without concurrent PH.
• Polycythemia if hypoxemic. • Leukocytosis 
with infectious lung disease. • Possible 
evidence of hypercoagulability.
• Arterial blood gases (hypoxemia). • Occult 
heartworm test. • Workup for PTE (urine 
protein : creatinine ratio, antithrombin III 
level, D ­dimer, coagulation profile, urine 
cortisol : creatinine ratio, adrenocorticotropic 
hormone stimulation test, dexamethasone 
suppression test). • Cytology of effusions.
IMAGING
• Dilated PA and/or torturous pulmonary 
vessels. • Enlarged RV and right atrium (RA). 
• Dilated caudal vena cava. • Pleural effusion. 
• Hepatomegaly. • Ascites. • Evidence of 
primary pulmonary disease, PTE, or HWD.
• RV concentric/eccentric hypertrophy. 
• Flattening of interventricular septum and/or 
paradoxical septal motion. • RA dilation. • PA 
dilation with decreased distensibility. • Pleural/
pericardial effusion. • Evidence of left heart 
disease, HWD, CHD, or PTE. • Asymmetric, 
notched pulmonary outflow tracing. • TR 
gradient, if present without pulmonic stenosis 
or PA stenosis, estimates systolic PH severity. 
◦ Systolic pressure gradient  between PA and RA 
estimated with spectral Doppler using modified 
Bernoulli equation: 4 × (peak TR velocity)2. 
◦ Pressure gradient >35 mmHg (TR velocity 
≥3.0 m/s) suggestive of PH. ◦ Gradient 
determines severity—mild: 35–50 mmHg; 
moderate 51–80 mmHg; severe: >80–mmHg. 
• Pulmonary valve insufficiency (PI), if present 
without PA stenosis, estimates diastolic PH 
severity. ◦ Diastolic pressure gradient between 
PA and RV estimated with spectral Doppler 
using modified Bernoulli equation: 4 × (end PI 
velocity)2. ◦ Pressure gradient >15 mmHg (end 
PI velocity >2.0 m/s) suggestive of PH.
CT/MRI
May be of value if pulmonary neoplasia or 
other infiltrative/obstructive disease.
T ranstracheal wash, bronchoscopy/
bronchoalveolar lavage, or lung aspirate/
biopsy may be of value if evidence of primary 

Canine and Feline, Seventh Edition  705
HECG
• Right mean electrical axis deviation. • Deep 
S waves (leads I, II, III, and aVF), • Widened 
QRS complex. • P­pulmonale. • ST segment 
depression/elevation. • Hypoxia ­induced 
arrhythmias (ventricular premature complexes 
[VPCs]).
Cardiac Catheterization and Pulmonary 
• Gold standard for diagnosis. • Uncommonly 
performed due to risk and usefulness of 
echocardiography. • Indicated if necessary to 
confirm diagnosis or cause.
Depend on underlying disease and severity—
primary pulmonary lesions; PTE; dilated PA/
RV/RA/vena cava; heartworms; pleural/
pericardial/abdominal effusions; medial 
hypertrophy, intimal proliferation, and sclerosis 
of pulmonary vessels; necrotizing arteritis.
  TREATMENT
• Hospitalize patients in severe respiratory 
distress. • Perform diagnostics based on 
patient stability.
• Judicious fluid therapy may help improve 
pulmonary blood flow. • Risk of CHF must be 
considered. • Maintain low ­stress environment.
• Prognosis varies with the underlying disease 
but generally very guarded. • Avoid respiratory 
triggers—heat/humidity extremes, secondhand 
smoke, high altitudes.
Surgical heartworm extraction is a consideration 
in patients with severe infestation.
• T reat the primary underlying disease 
whenever possible. • The ideal therapeutic 
agent for PH causes pulmonary vasodilation 
without causing significant systemic 
Oxygen
• T reatment of choice but long ­term 
administration unfeasible. • Useful in acute 
setting to correct hypoxia and cause 
pulmonary vasodilation.Phosphodiesterase Type V (PDE5) 
• Inhibit the breakdown of cyclic guanosine 
monophosphate (cGMP) causing increased nitric 
oxide and pulmonary vasodilation. • Avoid other 
drugs with similar effects (nitrates). • Sildenafil 
(1–2 mg/kg q8–12h)—drug of choice for most 
causes of PH in dogs. • Tadalafil—limited 
studies suggest benefit in dogs.
Phosphodiesterase Type III (PDE3) 
Inhibitor
• Pimobendan. • Causes pulmonary and 
systemic vasodilation. • Positive inotropic effect 
supports right heart dysfunction. • Indicated if 
PH secondary to left heart disease. • Unclear if 
useful with other causes of PH.
Other Vasodilators
• Limited benefit due to concurrent systemic 
vasodilation and hypotension. • Important in 
PH due to left heart disease. • Amlodipine, 
hydralazine, and angiotensin ­converting 
• May help patients with pulmonary disease. 
• Sympathomimetics (e.g., terbutaline). 
• Methylxanthines (e.g., theophylline)—may 
also cause mild PA vasodilation.
• Common therapy for all causes of PH due to 
primary and/or secondary thromboembolism 
in humans. • Use in companion animals 
unclear except in patients with PTE.
Thrombolytics
• Streptokinase and tissue plasminogen 
activator indications and effectiveness debated 
in companion animals. • Likely only 
indicated if acute PTE with significant 
cardiac compromise.
Anti-inflammatories and Antibiotics
• Steroids may help if cause of PH has 
inflammatory component (e.g., HWD or 
primary pulmonary disease). • Antibiotics if 
bacterial component.
Other Therapies
• No large veterinary clinical trials to 
support use. • Endothelin receptor 
antagonists (Bosentan®)—pulmonary 
vasodilator that improves outcome in 
humans; cost prohibitive in veterinary 
patients. • Platelet ­derived growth factor 
antagonists (toceranib, sorafenib, imatinib)—  
shown to decrease right heart pressure in rat 
PH model; preliminary studies of imatanib 
in dogs is promising. • L­arginine—possible 
benefit due to conversion to nitric oxide.CONTRAINDICATIONS
• Respiratory depressants. • Cardiac 
myocardial depressants (e.g., beta blockers). 
• Bronchoconstrictors (e.g., nonspecific beta 
blockers). • Vasoconstrictors.
• Vasodilators can cause systemic hypotension. 
• Pulmonary vasodilation in patients with left 
heart disease may induce pulmonary edema. 
• Bronchodilators can cause tachycardia and 
hyperexcitability. • Hypovolemia may reduce 
pulmonary blood flow.
  FOLLOW-UP
• Serial echocardiography to assess 
improvement/progression. • Repeat thoracic 
radiographs, ECG, labwork, blood pressure 
as needed.
• Right ­sided CHF . • Syncope. 
• Arrhythmias. • Sudden death.
• Based on ability to reverse underlying 
disease. • Often very guarded prognosis.
• CHD = congenital heart disease.
• HWD = heartworm disease.
• LA = left atrium.
• PA = pulmonary artery.
• PI = pulmonary valve insufficiency.
• RA = right atrium.
• RV = right ventricle.
• TR = tricuspid valve regurgitation.
• VPCs = ventricular premature complexes.
Poser H, Guglielmini C. Pulmonary 
hypertension in the dog. Acta Veterinaria ­
Beograd 2016, 66:1–25.
Authors  Donald P . Schrope and Jennifer M. 
Mulz
available online(continued)  Hypertension, Pulmonary

706  Blackwell’s Five-Minute Veterinary Consult  
HHypertension, Systemic Arterial
  BASICS
Sustained increase in arterial blood pressure, 
corresponding to systolic BP (SBP) ≥160 mmHg 
confirmed during multiple measurement 
sessions. BP increases may be transient and 
related to the measurement process 
(situational or “white-coat” hypertension), or 
sustained and pathologic. In veterinary 
patients, systemic arterial hypertension (HT) 
usually occurs in association with a clinical 
disease or treatment known to cause HT and 
is categorized as secondary. If an underlying 
disease is not present or able to be 
determined, HT is considered idiopathic.
• BP is the force exerted by a blood column 
against the vessel wall, and is determined by 
cardiac output, aortic impedance and 
systemic vascular resistance.
• Normally, BP is under close regulation, 
such that rapid or wide swings are avoided.
• Factors that favor BP increases by 
augmenting cardiac output (e.g., increases in 
intravascular volume, heart rate, or myocardial 
contractility) or systemic vascular resistance 
(e.g., arteriolar vasoconstriction, increased 
blood viscosity) are usually balanced by 
autonomic, renal, and local vascular responses 
that restore normal BP .
• Systemic HT may develop in association 
with diseases or pharmacologic agents that 
overwhelm or interfere with normal 
homeostatic mechanisms or with vascular 
responsiveness to these mechanisms.
• Chronic, sustained BP increases may cause 
injury to several organs, referred to as target 
organ damage (TOD).
• Nervous.
GENETICS
Rare instances of familial idiopathic HT are 
reported.
• Prevalence estimates are difficult to 
interpret due to differences in HT definitions, 
inclusion criteria, and measurement 
techniques among studies.
• Pathologic HT are rare in young, healthy 
• Reported prevalence in HT-associated 
diseases—chronic kidney disease (CKD), 
9–93% (dogs) and 19–65% (cats); diabetes 
mellitus, 24–67% (dogs) and 0–15% (cats); 
hyperadrenocorticism, 20–80% (dogs); 
hyperthyroidism, 5–25% (cats); pheochromo -
cytoma, 43–86% (dogs).SIGNALMENT
Species
None
• Usually older animals; median age 13–15 
years (cats).
• May be noted in younger animals, especially 
those affected by infectious (e.g., leptospirosis) 
or heritable (e.g., polycystic kidney disease, 
renal dysplasia) disease.
SIGNS
Clinical signs vary with affected target organ 
and underlying disease; may be apparently 
asymptomatic or display signs that are acute, 
severe, or rapidly progressive.
• Signs attributable to underlying disease (e.g., 
polyuria/polydipsia, anorexia, vomiting, weight 
loss with CKD; hindlimb weakness, cervical 
ventroflexion with hyperaldosteronism).
• Acute-onset or progressive blindness.
• Altered mental state, lethargy, seizures 
(generalized or focal), or ataxia.
• Rarely, respiratory signs due to congestive 
heart failure (CHF), e.g., dyspnea/orthopnea 
(cats/dogs), cough (dogs).
• Epistaxis (rare).
• Headaches, blurred vision, and anxiety, 
reported by people with HT, may manifest as 
nonspecific signs in dogs and cats.
• Ocular—blindness, mydriasis, exudative 
retinal detachment, retinal hemorrhage/
edema, retinal vascular tortuosity or 
perivascular edema, vitreal hemorrhage, 
bullous retinal detachment, hyphema, 
glaucoma, retinal degeneration.
• Neurologic—abnormal mentation, central 
blindness, nystagmus, ataxia.
• Renal—palpable renal abnormalities.
• Cardiovascular—heart murmur, arrhythmia, 
gallop sound, pulmonary crackles.
CAUSES
Subclinical CKD thought to contribute in 
some cases.
Secondary Hypertension
• CKD.
• Acute kidney injury (AKI).
• Pheochromocytoma.
• Primary hyperaldosteronism.
• Drug-related—glucocorticoids 
(uncommon), mineralocorticoids (high dosages), erythropoietin/darbepoetin, 
phenylpropanolamine, phenylephrine, 
ephedrine, toceranib phosphate.
• Intoxicants—cocaine, methamphetamine/
amphetamine, 5-hydroxytryptophan.
Renal disease or endocrinopathy.
  DIAGNOSIS
Differential signs—differentiate from other 
causes of acute-onset blindness, central 
neurologic signs, CHF , or epistaxis, 
depending on presenting signs and clinical 
findings.
• Abnormalities vary depending on 
• Packed cell volume may be decreased 
(CKD) or mildly increased (hyperthyroidism).
• CBC may reveal stress leukogram and/or 
thrombocytosis (hyperadrenocorticism).
• May note azotemia, hyperphosphatemia, 
hyperkalemia (AKI, CKD); hyperglycemia 
(diabetes mellitus); increased serum alkaline 
phosphatase (hyperadrenocorticism); increased 
serum alanine aminotransferase (hyperthy -
roidism); hypokalemia (hyperaldosteronism).
• Urinalysis may reveal low urine specific 
gravity, proteinuria, hematuria, pyuria, 
bactiuria (AKI, CKD, hyperadrenocorticism); 
glucosuria (diabetes mellitus).
• Assessment of glomerular filtration rate 
may detect early renal dysfunction.
• Urinary protein : creatinine ratio may 
disclose proteinuria.
• Serum total T4 concentration, T3 suppression 
test to evaluate for hyperthyroidism (cats).
• Serum T3, T4, free T3, free T4, and 
thyroid-stimulating hormone concentrations; 
T3 and T4 autoantibodies to evaluate for 
hypothyroidism (dogs).
• Screening tests for hyperadrenocorticism in 
dogs with other suggestive findings.
• Plasma aldosterone concentration if 
primary hyperaldosteronism suspected (cats).
• Plasma and urinary catecholamine 
concentrations if pheochromocytoma suspected.
IMAGING
• Abdominal ultrasonography to evaluate 
kidneys, liver, and adrenal glands.
• Echocardiography to evaluate for cardiac 
TOD—may be normal, or disclose left 
ventricular concentric and/or eccentric 
hypertrophy, diastolic dysfunction, left atrial 
• CT or MRI if cerebral hemorrhage, 
hyperadrenocorticism suspected.
• Thyroid scintigraphy to evaluate 

Canine and Feline, Seventh Edition  707
• Diagnosis requires documentation of 
persistently (i.e., during ≥2 sessions, 
performed on different days) high SBP , using 
reliable direct or indirect measurement 
methods.
• Methods should be standardized to avoid 
inaccuracies caused by common technical 
errors.
• Substantial effort should be made to 
minimize patient stress to reduce risk of 
falsely diagnosing “true” HT in patient with 
situational HT.
• See Suggested Reading to consult 
detailed published guidelines for BP 
Direct (Invasive) BP Measurement 
Methods
• Gold standard—involve catheterization or 
needle puncture of peripheral artery.
• Reserved for monitoring under anesthesia 
or during emergency management of severe 
HT.
Indirect (Noninvasive) BP Measurement 
Methods
• More clinically useful than direct methods 
for outpatient setting.
• Utilize devices that rely on Doppler 
ultrasonography or oscillometry.
• Require placement of inflatable cuff to 
temporarily occlude arterial blood flow in 
extremity by applying external, compressive 
force.
Ancillary Diagnostics
Fundoscopic examination to evaluate for 
retinal lesions.
• Widespread, multisystemic arteriolosclerosis.
• Increased cardiac mass due to left 
ventricular hypertrophy.
• Aortic aneurysm/dissection (rare).
• Lesions associated with underlying disease.
  TREATMENT
Treatment Guidelines for Dogs and Cats
• General goal to reverse/limit ongoing TOD 
and prevent future TOD.
• If identified, treatment of underlying 
disease may resolve HT.
• Antihypertensive therapy indicated in dogs 
and cats with:
◦ SBP ≥160 mmHg on two or more 
occasions for which situational 
hypertension considered unlikely.
◦ SBP ≥160 mmHg on single occasion if 
clear evidence of ongoing neurologic or 
ocular TOD.
• Animals without evidence of TOD and 
mildly increased SBP (140–159 mmHg, “prehypertensive”), or suspected situational 
HT, should not be treated.
• Therapeutic targets—ideally, normotension 
(SBP 120–140 mmHg); SBP <160 mmHg at 
minimum.
• Gradual (i.e., over several weeks) reduction 
in BP should be targeted.
• HT considered an emergency if severe 
neurologic or ocular TOD is present; in these 
cases, goal is to cautiously reduce SBP to 
approximately 160 mmHg over 3–6 hours 
and to <140 mmHg over 1–2 days, with 
continuous/frequent BP monitoring.
Usually managed on outpatient basis. 
Inpatient care may be necessary depending on 
underlying condition and severity of target 
organ damage.
ACTIVITY
DIET
• Dietary sodium restriction is controversial.
• Avoid high sodium intake.
• Unless underlying cause is curable or 
controllable, patient is likely to require 
lifelong antihypertensive therapy.
• HT may persist or develop even with 
control of underlying disease (e.g., 
hyperthyroidism).
• Multiple agents and periodic dosage 
adjustments may be required for adequate 
control of HT.
• Frequent monitoring necessary until 
adequate BP control is achieved.
May be indicated for pheochromocytoma, 
primary hyperaldosteronism, hyperthyroidism, 
and some forms of hyperadrenocorticism.
• Depend on underlying disease (e.g., 
adrenergic antagonists preferred in patients with 
pheochromocytoma, aldosterone antagonists in 
those with primary aldosteronism).
• Cats—amlodipine or telmisartan first line for 
SBP 160–200 mmHg; amlodipine first line if 
SBP >200 mmHg or ocular/neurologic TOD; 
angiotensin-converting enzyme (ACE) inhibitor 
or telmisartan may be added if proteinuria or 
poor control with amlodipine alone.
• Dogs—ACE inhibitor or angiotensin 
receptor blocker (ARB) first line; amlodipine 
coadministered as first line if SBP >200 mmHg, 
or added if SBP 160–200 mmHg and poor 
control with ACE inhibitor or ARB.
• In hypertensive emergency (HT with severe 
ocular or neurologic TOD), parenteral hydralazine, sodium nitroprusside, or 
fenoldopam can be used; continuous direct 
BP monitoring is necessary in these cases.
Dihydropyridine Calcium Channel 
Blocker
Amlodipine—dogs: 0.1–0.5 mg/kg PO q24h; 
cats: 0.625–1.25 mg/cat PO q24h (consider 
1.25 mg/cat if SBP >200 mmHg; may be 
increased to 2.5 mg/cat if necessary).
ACE Inhibitor
Enalapril or benazepril—dogs: 0.5–1.0 mg/kg 
PO q12h; cats: 0.5 mg/kg PO q12–24h.
ARB
Telmisartan—dogs: 1.0 mg/kg PO q24h; 
cats: 2.0 mg/kg PO q 24h; in United States 
labeled to start with 1.5 mg/kg PO BID 
protocol for 2 weeks and then adjust to 
2.0 mg/kg q24h.
Direct-Acting Vasodilator
Hydralazine—dogs: 0.5 mg/kg PO q12h, 
stepwise increase to 3 mg/kg PO q12h if 
needed; cats: 2.5 mg/cat q12–24h.
Alpha-Adrenergic Receptor Antagonist
Phenoxybenzamine—dogs: 0.25 mg/kg PO 
q8–12h; cats: 2.5 mg/cat PO q8–12h.
Aldosterone Antagonist
Spironolactone—dogs and cats: 1.0–2.0 mg/
kg PO q12h.
Decrease or discontinue vasoconstricting 
drugs (e.g., phenylpropanolamine).
• Abrupt BP reduction and hypotension 
(SBP <120 mmHg) should be avoided; use of 
rapidly acting drugs or combinations of 
vasodilators increases this risk.
• Direct arteriolar vasodilators and IV 
antihypertensives may cause reflex tachycardia.
• Use of antihypertensives in combination 
increases risk of hypotension.
• Hyperkalemia may result from coadmini -
stration of any combination of ACE 
inhibitor, ARB, and spironolactone.
For Hypertensive Emergency
• Sodium nitroprusside (inorganic nitrate)—
dogs and cats: 0.5–5  μg/kg/min IV, start low 
and increase by increments of 0.1–0.5  μg/kg/
min to effect.
• Hydralazine (direct arteriolar vasodilator)—
dogs: 0.5–2 mg/kg SC/IM q8–12h or 
0.1–0.5 mg/kg IV q2–8h, CRI 1.5–5.0  μg/
kg/min; cats: 1.0–2.5 mg/cat SC.
• Fenoldopam (dopamine-1 antagonist)—dogs 
and cats: 0.1–1.6  μg/kg/min; start low, increase 
by increments of 0.1  μg/kg/min to effect.(continued)  Hypertension, Systemic Arterial

708  Blackwell’s Five-Minute Veterinary Consult  
H  FOLLOW-UP
• BP and manifestations of ocular or 
neurologic TOD should be checked weekly 
(or every 1–3 days if severe TOD) until 
normotension (SBP 120–140 mmHg) 
achieved (ideally), or SBP <160 mmHg (at 
minimum).
• Periodic monitoring of laboratory tests to 
evaluate for side effects of medications and 
clinical response (e.g., proteinuria, hematuria, 
anemia, thrombocytopenia, potassium 
balance, sodium balance, azotemia).
• Progression of underlying renal disease.
• Retinopathy, choroidopathy.
• Encephalopathy, cerebral vascular accident.
• CHF (uncommon), aortic aneurysm/
dissection/rupture (rare).
• Gingival hyperplasia may develop with 
amlodipine treatment in dogs.
• Facial dermatitis/excoriation may develop with 
spironolactone treatment in cats (uncommon).
• T reatment of systemic hypertension may 
reverse or slow progression of TOD.
• Rapid and complete improvement of 
neurologic signs (usually within 24–48 hours) 
is expected with adequate BP control.
• Improvement/resolution of visual deficits 
may take weeks with BP control; most blind 
eyes do not regain normal vision.  MISCELLANEOUS
• CKD.
• Endocrinopathies.
• CKD.
None, unless underlying leptospirosis.
Pregnancy may exacerbate HT.
SYNONYMS
• High blood pressure.
SEE ALSO
Cats.
Dogs.
• AKI = acute kidney injury.• ARB = angiotensin receptor blocker.
• HT = systemic arterial hypertension.
• SBP = systolic arterial blood pressure.
• TOD = target organ damage.
https://icatcare.org/vets/guidelines/
hypertension-cats
Acierno MJ, Brown S, Coleman AE, et al. 
ACVIM consensus statement: guidelines for 
the identification, evaluation, and 
management of systemic hypertension in 
dogs and cats. J Vet Intern Med 2018, 
32(6):1803–1822.
Carter J. Hypertensive ocular disease in cats: a 
guide to fundic lesions to facilitate early 
diagnosis. J Feline Med Surg 2019, 21:35–45.
Jepson RE, Feline systemic hypertension: 
classification and pathogenesis. J Feline 
Med Surg 2011, 13(1):25–34.
Taylor SS, Sparkes AH, Briscoe K, et al. 
ISFM consensus guidelines on the diagnosis 
and management of hypertension in cats. J 
Feline Med Surg 2017, 19(3):288–303.
Author  Amanda E. Coleman
Rosie A. Henik
available onlineHypertension, Systemic Arterial  (continued)

Canine and Feline, Seventh Edition  709
HHyperthyroidism
  BASICS
A state of increased metabolism caused by 
increased circulating concentrations of thyroid 
hormone.
• Feline hyperthyroidism most often caused by 
benign adenomatous hyperplasia or follicular 
cell adenoma, causing increased secretion of 
thyroxine (T4) and triiodothyronine (T3). 
• Naturally occurring hyperthyroidism rare in 
dogs; most often malignant carcinoma (<2% of 
cats have malignant thyroid carcinoma). 
• Oversupplementation with exogenous thyroid 
hormone may cause hyperthyroidism in dogs.
• Cardiovascular—systemic hypertension, 
thyrotoxic cardiomyopathy. • Gastrointestinal 
(GI)—malabsorption, hypermotility. 
• Nervous/behavioral—restlessness, irritability, 
aggression, vocalization, pacing. • Urologic—
increased glomerular filtration rate (GFR). 
• Musculoskeletal—catabolism, cachexia.
GENETICS
• Most common feline endocrinopathy; 
affects 3–8% of cats >10 years old. • Rare in 
dogs.
• Cats 4–22 years old; mean age of onset is 
13 years. • <5% of affected cats <8 years old. 
• Most common in dogs >10 years old.
SIGNS
• Signs related to increased metabolism. 
• Small number of cats show atypical signs; 
the human term “apathetic hyperthyroidism” 
is characterized by lethargy, decreased 
appetite, and muscle weakness; signs may be 
more common with advanced 
• Weight loss. • Polyphagia. • Hyperactivity/
irritability/restlessness. • Polyuria/polydipsia. 
• Vomiting. • Diarrhea. • Increased vocaliza -
tion. • Tachypnea. • Muscle weakness.
• Cachexia/muscle loss. • Palpable thyroid 
gland (unilateral or bilateral). • Tachycardia/
heart murmur/gallop rhythm. • Systemic 
hypertension/retinopathy. • Unkempt hair/
hair loss. • Thickened nails. • Ventroflexion 
of neck (advanced disease).
CAUSES
• In cats, benign adenomatous hyperplasia 
and follicular cell adenoma lead to oversecre-
tion of T4 and T3; thyroid carcinoma is rare. • In dogs, thyroid carcinoma is more likely; 
hyperthyroidism in dogs may be secondary to 
oversupplementation of T4.
• Increased risk with aging. • Decreased risk 
in Burmese, Tonkinese, Persian, Siamese, 
Abyssinian, and British shorthair cats; 
possible increased risk in domestic longhair 
cats. • Multifactorial environmental 
contributors are possible, including bisphenol 
A (BPA) associated with canned food diets, 
and polybrominated diphenyl ether (PBDE) 
flame retardants, but further study is needed.
  DIAGNOSIS
• Any of the differentials for hyperthyroidism 
can reflect concurrent disease. • Neoplasia. 
• Inflammatory bowel conditions. • Diabetes 
mellitus. • Chronic kidney disease. 
• CBC—mild packed cell volume (PCV) 
elevation or stress leukogram. • Elevated 
alanine aminotransferase (ALT) activity is 
common. • Elevated alkaline phosphatase 
(ALP), aspartate aminotransferase (AST) 
activities, and blood urea nitrogen, creati -
nine, phosphorus, bilirubin, and glucose 
concentrations may be seen. • Urinalysis 
(UA) shows variable urine specific gravity; 
pre-treatment specific gravity does not 
predict post-treatment renal function. 
• Glucosuria and evidence of urinary tract 
• Elevated serum total T4 (TT4) 
concentration is diagnostic for 
hyperthyroidism in cats with clinical signs. 
◦ T4 concentrations naturally decrease with 
age; early hyperthyroid cats may have T4 
levels in high-normal range. ◦ T4 
concentration may be decreased by 
concurrent disease. • Free T4 concentration 
measured by equilibrium dialysis may be 
helpful in cats with concurrent disease or 
early hyperthyroidism, but is not a screening 
test. • T3 concentration is not useful for 
diagnosis in cats. • Thyroid-stimulating 
hormone (TSH) concentration should not be 
used for diagnosis in cats. • T3 suppression 
test or thyrotropin-releasing hormone (TRH) 
stimulation test can help to confirm diagnosis 
in mild cases. • Fructosamine concentration 
may be decreased by concurrent 
hyperthyroidism. • Cardiac biomarker 
concentrations ( N-terminal pro brain 
natriuretic peptide, cardiac toponin I) may be 
elevated; myocardial disease and biomarkers 
may return to normal after control of 
hyperthyroidism.IMAGING
• Thoracic and abdominal radiography 
helpful to evaluate for neoplasia and cardiac 
disease. • Abdominal ultrasound helpful in 
determining concurrent disease. 
• Echocardiography to evaluate cardiac 
function. • Thyroid scintigraphy can 
determine location of abnormal and ectopic 
thyroid tissues.
• BP measurement is part of baseline 
database. • GFR measurement is possible but 
not always practical.
• Multinodular adenomatous hyperplasia can 
be unilateral or bilateral (98% of cats). 
• Thyroid carcinoma in dogs and <2% of 
hyperthyroid cats.
  TREATMENT
• Advanced hyperthyroidism with concurrent 
congestive heart failure requires hospitaliza-
tion for stabilization. • Most cases managed 
on an outpatient basis. • Radioactive iodine 
and surgical treatments require 
ACTIVITY
No activity restrictions.
DIET
• Because of increased metabolism and 
hypermotility of intestinal tract, highly 
digestible diets preferred. • Malabsorption 
improves with resolution of hyperthyroid state. 
• Vitamin B12 supplementation may be 
helpful. • An iodine-deficient therapeutic diet 
is available and effective in appropriate 
situations.
• Hyperthyroidism in cats is common and 
treatable. • T reatment with medication or 
diet restriction is lifelong. • Medication 
dosing needs to be monitored regularly and 
adjusted accordingly. • Comorbidities are 
possible. • Hyperthyroidism in dogs is 
usually a malignancy and carries a poor 
long-term prognosis. • Possible side effects of 
medication. • Surgical thyroidectomy—anes-
thetic risks, risk of damage to parathyroid 
glands. • In some cases, radioactive iodine 
(I-131) treatment may need to be repeated. 
• Resolution of thyrotoxicosis may reveal 
other, previously masked conditions (e.g., 
renal disease).
• Surgical thyroidectomy is an accepted 
treatment option. • Thyroidectomy for 
carcinoma is not curative, but may be helpful 
with or without subsequent radioactive iodine 

710  Blackwell’s Five-Minute Veterinary Consult  
H  MEDICATIONS
• I-131 is treatment of choice for hyperthy-
roidism. • Methimazole (2.5–5 mg/cat PO 
q12–24h) is most common medication. 
◦ Methimazole should be dosed below 
expected therapeutic dose and titrated upward 
to minimize side effects. ◦ T ransdermal 
methimazole is available and effective; ideally, 
initial management with oral methimazole 
will stabilize patient, then transition to 
transdermal; resolution may be prolonged if 
treatment initiated with transdermal 
medication. ◦ Methimazole may cause 
anorexia, vomiting, skin excoriations, 
thrombocytopenia, hepatopathy, and hypo- 
thyroidism; side effects occur within first 
weeks to months of treatment. ◦ Anorexia, 
vomiting, and skin excoriations can be 
mitigated by starting at very low doses of 
methimazole and increasing to therapeutic 
levels; cessation of drug can resolve these 
issues, and restarting with transdermal 
methimazole may avoid recurrence of GI side 
effects. ◦ Bleeding disorders, bone marrow 
dyscrasias, and hepatic issues require 
discontinuation of methimazole and choosing 
an alternative therapy. ◦ Severe blood 
dyscrasias may require hospitalization and 
supportive care, but should resolve with 
appropriate treatment. • Atenolol may be 
used for severe tachycardia.
Concurrent use of phenobarbital may reduce 
effectiveness of methimazole.
• Carbimazole—converted to methimazole 
after absorption; effective, may have fewer 
side effects than methimazole; not available in 
United States. • Propylthiouracil—not 
recommended. • Ipodate—for short-term 
treatment only, not effective for most 
hyperthyroid cats; not recommended in most 
cases.
  FOLLOW-UP
• Regardless of treatment option, GFR and 
renal function may decline after treatment, 
but will stabilize within 1 month of thyroid 
control. • I-131—physical exam (PE), BP , 
T4, serum chemistry, and UA at 1, 3, 6, and 
12 months post treatment. 
• Methimazole—PE, CBC, serum  chemistry, 
T4, and UA every 2–4 weeks after starting treatment and after every dose change until 
T4 is stabilized between 1 and 2.5  μg/L. 
• In cats with renal insufficiency, serum T4 
should be maintained in upper half of 
reference interval. • Thyroidectomy—
hypocalcemia can occur within several days 
post surgery; monitor for postoperative 
laryngeal paralysis; PE, T4, serum chemistry, 
and UA 2–4 weeks post surgery, then every 
3–6 months; supplementation should not 
be started postsurgically unless T4 levels 
remain low after 3 months; hypothyroidism 
may be transient with subtotal thyroidec -
tomy. • Therapeutic diet—PE, BP , serum 
chemistry, CBC, T4, and UA every 4–6 
months; may take as long as 6 months for 
cats with severe T4 elevations to become 
euthyroid, if at all.
N/A
• Fatal, if untreated. • Complications of 
thyroidectomy include hypothyroidism, 
hypoparathyroidism, laryngeal paralysis. 
• I-131, antithyroid drugs, and thyroidec-
tomy can all lead to hypothyroidism; proper 
dosing of I-131 and methimazole is impera-
tive. • Iatrogenic hypothyroidism associated 
with worsening renal function and decreased 
survival.
• Prognosis is excellent in cats without 
concurrent disease. • Cats on methimazole 
are likely to relapse if medication is not 
administered correctly. • Cats eating a 
therapeutic diet who do not strictly follow 
diet will not be successful. • Post I-131 
treatment—mean survival time is 4 years. 
• T reatment with methimazole—mean 
survival time is 2 years. • Overall mean 
survival time can be up to 5.3 years. • Cats 
with preexisting renal disease have a poorer 
prognosis. • Cats and dogs with carcinoma 
have a poor prognosis—best option for 
treatment may be surgical debulking of tumor 
followed by high dose I-131; recurrence is 
common.
ASSOCIATED CONTITIONS
• Because hyperthyroidism is life-threatening, 
treatment of all hyperthyroid cats is recom-
mended, with concurrent management of any 
comorbidities. • Less aggressive treatment 
options should be considered for cats with 
advanced (IRIS stage 3–4) renal disease.
Mature to geriatric cats and dogs.ZOONOTIC POTENTIAL
N/A
N/A
SYNONYMS
• Thyrotoxicosis. • Plummer’s disease.
SEE ALSO
• BPA = bisphenol A.
• I-121 = radioactive iodine.
• PBDE = polybrominated diphenyl ether. 
• PE = Physical exam.
• T3 = triiodothyronine.
• TRH = thyrotropin-releasing hormone.
• TT4 = total thyroxine.
• UA = urinalysis.
https://www.catvets.com/public/PDFs/Client 
Brochures/Hyperthyroidism-WebView.pdf
Carney HC, Ward CR, Bailey SJ, et al. 2016 
AAFP guidelines for the management of 
feline hyperthyroidism. J Fel Med Surg 
2016, 18:400–416.
Scott-Moncrief JC. Feline hyperthyroidism. 
In: Feldman EC, Nelson RW, Reusch CE, 
et al., eds., Canine and Feline Endocrinology 
and Reproduction, 4th ed. St. Louis, MO: 
Elsevier, 2015, pp. 136–195.
Stock E, Daminet S, Paepe D, et al. 
Evaluation of renal perfusion in 
hyperthyroid cats before and after 
radioiodine treatment. J Vet Intern Med 
2017, 31:1658–1663.
Walter KM, Lin YP , Kass PH, Puschner B. 
Association of polybrominated diphenyl ethers 
(PBDEs) and polychlorinated biphenyls 
(PCBs) with hyperthyroidism in domestic 
felines: sentinels for thyroid hormone 
disruption. BMC Vet Res 2017, 13:120.
Author  Renee Rucinsky
available onlineHyperthyroidism  (continued)

Canine and Feline, Seventh Edition  711
HHypertrophic Osteodystrophy
  BASICS
An inflammatory disease of bone that affects 
rapidly growing giant- and large-breed puppies.
• Characterized by nonseptic, suppurative 
inflammation within metaphyseal trabeculae 
• Rapidly growing bones more severely 
affected (distal radius, ulna, and tibia).
• Metaphysis—widened owing to perimeta -
physeal swelling and bone deposition.
• T rabecular microfracture and metaphyseal 
separation—occur adjacent and parallel to the 
physis.
• Bone formation defective.
• Ossifying periostitis—may be extensive and 
in some cases may bridge the physis, hindering 
growth.
• Etiology unknown.
• Musculoskeletal—symmetric distribution; 
distal forelimbs most severely affected; may 
note soft tissue mineralization in other 
organs; widened costochondral junctions.
• Respiratory—interstitial pneumonia.
GENETICS
Suspect hyperreactivity to immune stimula-
tion (vaccination).
Low
Northeastern United States—highest in fall; 
lowest in winter.
Species
Dog
• Large and giant breeds.
• Great Danes; Weimaraners—most 
common.
• Reported—Irish wolfhounds; Saint 
Bernards; kuvaszes; Irish setters; Doberman 
pinschers; German shepherds; Labrador 
retrievers; boxers; Chesapeake Bay retriever; 
golden retriever; Irish setter; others.
• Affects puppies 3–6 months old.
• Range of onset—2–8 months of age.
Males 2.3 times more than females.
SIGNS
Lameness—may be episodic; degree varies 
from mild to non-weight-bearing; initial 
episode may resolve with or without relapse.Historical Findings
• Depend on severity of the episode.
• Owners often describe a depressed puppy 
that is reluctant to move.
• Inappetence—common.
• Painful.
• Shifting leg lameness.
• Lameness—symmetric, more severe in 
forelimbs.
• Metaphyses—painful; warm; swollen distal 
metaphyses of radius, ulna, and tibia.
• Pyrexia—as high as 41.1 °C (106 °F).
• Debilitation.
• Manifestations of systemic illness—
respiratory or gastrointestinal.
• Foot pad hyperkeratosis.
• Anemia.
CAUSES
Unknown; the following hypotheses have 
been proposed.
Metabolic
• Hypovitaminosis C—discounted; may be 
seen as a result of overuse of available vitamin 
C in hyperactive bone formation.
• Hypocuprosis—in rats but not in dogs.
• Overnutrition and oversupplementation—
association inconsistent.
• Incomplete occurrence in litters.
• Correcting diet does not always alter the 
course of the disease or eliminate relapses.
• Bacterial or fungal organisms—may be 
secondary when found.
• Not transmissible.
• Temporal association with canine distemper 
virus vaccination.
• Secondary development may depend on the 
timing of the neonate’s exposure.
Vaccination against canine distemper virus 
may precipitate an uncontrolled inflamma-
tory reaction in the osteogenic centers.
  DIAGNOSIS
• Panosteitis—no metaphyseal swelling; 
cottony intramedullary densities in long 
bones on radiographs.
• Septic metaphysitis/epiphysitis—radiographs 
of the extremities not typical of hypertrophic 
osteodystrophy; asymmetric; may note septic 
suppurative inflammation on needle aspiration of metaphyseal/epiphyseal lesions; hematologic 
findings implicate bacterial infection (neutrophilia 
plus left shift).
• Elbow dysplasia—no metaphyseal swelling; 
no fever; pain localized to the elbow(s); 
typical radiographic signs.
• Osteochondritis dissecans—no metaphyseal 
swelling or fever; pain localized to shoulder or 
elbow; subchondral defects on radiographs.
• Septic polyarthritis—septic suppurative 
inflammation on arthrocentesis; culture.
• Nonseptic polyarthritis—nonseptic 
suppurative inflammation on arthrocentesis.
• Do not positively contribute to diagnosis.
• Stress leukogram.
• Normal serum parameters.
• Hypocalcemia uncommon.
N/A
IMAGING
• Distal extremity radiographs—irregular 
radiolucent zones within metaphyses, parallel 
and adjacent to physes; flared metaphyses; 
extraperiosteal new bone extending up the 
diaphyses; mineralization of perimetaphyseal 
soft tissues; asynchronous growth in paired 
bones; cranial bowing; valgus deformity; 
usually bilaterally symmetric.
• Vertebrae, metacarpal bones, metatarsal 
bones, ribs, scapula, humerus, and mandible—
rarely affected.
• Thoracic radiographs—may reveal 
interstitial infiltrates.
• Distal metaphysis of the radius and 
ulna—most severe changes; similar 
abnormalities in all long bones.
• Gross—wide metaphysis; peripheral 
mineralization; soft tissue swelling.
• Nonseptic suppurative inflammation of the 
metaphysis (osteochondritis), especially 
adjacent to growth plates.
• Necrosis and probable secondary failure of 
osseous tissue deposition onto the calcified 
cartilage lattice of the primary spongiosa.
• T rabecular microfractures and impaction.
• Mineralization of perimetaphyseal soft tissues 
and soft tissues in other regions of the body.
  TREATMENT
• None specific.
• Supportive—from none to intensive care 
for severely affected puppies.
• Depends on the severity of the episode, 
pyrexia, and the patient’s ability to maintain 
normal hydration and willingness to eat.

712  Blackwell’s Five-Minute Veterinary Consult  
• Some patients will not stand or move—
prone to develop pressure sores; turn every 
2–4 hours to prevent sores and hypostatic 
congestion of the dependent lung.
• Intravenous fluid therapy—for dehydration; 
maintenance fluid thereafter.
ACTIVITY
• Restricted—running and jumping may 
exacerbate metaphyseal injury and result in 
further inflammation.
• Confine to a small well-padded area— 
• Leash-walking only.
DIET
• Normal commercial puppy ration.
• Avoid supplements.
• Warn the client of the disease’s relapsing 
nature.
• Inform client that bony deformities will 
remodel to some degree with time, but that 
bowing and valgus deformations are 
• Warn client that the more severe the disease, 
the more severe the bowing deformity.
• May implement surgical methods of 
alimentation (pharyngostomy tube, esophago -
stomy tube, gastrostomy tube)—in debilitated 
puppies that will not eat or drink and have 
frequently relapsing episodes of acute clinical 
signs.
• Corrective osteotomy if growth deformity 
develops from physeal disruption.
• Anti-inflammatory drugs—for pain and 
antipyretic effects; may try:
◦ Aspirin 10 mg/kg PO q12h.
◦ Carprofen 2.2 mg/kg IM/PO q12h.
◦ Deracoxib 1–2 mg/kg PO q24h; 
3–4 mg/kg PO q24h, 7-day limit.
◦ Firocoxib 5 mg/kg PO q24h,
◦ Grapiprant 2 mg/kg PO q24h, to 
animals >3.6 kg.
◦ Meloxicam—dogs: load 0.2 mg/kg PO, 
then 0.1 mg/kg PO q24h; cats: 0.1 mg/kg 
PO q24h—liquid.
• Analgesics—can be used in conjunction 
with anti-inflammatory medication:
◦ T ramadol 1–4 mg/kg PO q8–12h.
◦ Prednisone 0.5–1 mg/kg PO q24h; may 
cause physeal growth disturbances.
◦ Opiates may be needed in severe cases.CONTRAINDICATIONS
Vitamin C—may be contraindicated; may 
accelerate dystrophic calcification and 
decrease bone remodeling.
• Avoid immunosuppressive drugs if 
secondary infection is present.
(NSAIDs)—may cause gastric ulceration; 
watch for hematemesis or melena; never  use 
in conjunction with other NSAIDs or 
steroids.
None
None
  FOLLOW-UP
Signs of improvement—less metaphyseal 
sensitivity; patient gets up; appetite improves; 
pyrexia resolves.
N/A
• Permanent bowing deformities due to 
premature asymmetric physeal closure.
• Secondary bacterial infection.
• Pressure sores.
• Muscle fasciculations, seizure—with 
hypocalcemia.
• May see secondary septicemia.
• Recurrence.
• Death.
• Course—days to weeks.
• Most patients—one or two episodes and 
recover.
• Some patients—seem to have intractable 
relapsing episodes of pain and pyrexia; rarely 
die or are euthanized.
• Prognosis—usually good; guarded with 
multiple relapses or complicating secondary 
problems.
• Persistent bowing deformity—eliminates 
many purebred puppies from the show ring.
None proven.AGE-RELATED FACTORS
Vaccination (canine distemper virus).
None
Occurs only in juveniles.
SYNONYMS
• Metaphyseal osteopathy.
• Vitamin C deficiency.
• Scurvy.
• Moller Barlow’s disease.
• Osteodystrophy II.
SEE ALSO
• Elbow Dysplasia.
• Osteochondrosis.
drug.
Abeles V, Harrus S, Amgles JM. Hypertrophic 
osteodystrophy in six Weimaramer puppies 
associated with systemic signs. Vet Record 
1999, 145(5):130–134.
Crumlish PT, Sweeney T, Jones B, Angles JM. 
Hypertrophic osteodystrophy in the 
Weimaraner dog: lack of association 
between DQA1 alleles of the canine MHC 
and hypertrophic osteodystrophy. Vet J 
2006, 171:308–313.
Demko J, McLaughlin R. Developmental 
orthopedic disease. Vet Clin North Am 
Small Anim Pract 2005, 35(5):1111–1135.
Foale RD, Herrtgae ME, Day MJ. 
Retrospective study of 25 young 
Weimaraners with low serum immuno-
globulin concentrations and inflammatory 
disease. Vet Record 2003, 153:553–558.
Franklin MA, Rochat MC, Broaddus KD. 
Hypertrophic osteodystrophy of the 
proximal humerus in two dogs. J Am Anim 
Hosp Assoc 2008, 44(6):342–346.
Harrus S, Waner T, Aizenberg I, et al. 
Development of hypertrophic osteodystro-
phy and antibody response in a litter of 
vaccinated Weimaraner puppies. J Small 
Anim Pract 2002, 43:27–31.
available onlineHypertrophic Osteodystrophy  (continued)

Canine and Feline, Seventh Edition  713
HHypertrophic Osteopathy
  BASICS
OVERVIEW
• Disease of the distal extremities resulting 
from peripheral blood flow changes that 
stimulate an overgrowth of vascular 
connective tissue and subsequent periosteal 
proliferation.
• Pathogenesis—speculative; increased blood 
circulation in the limb due to neural or 
humoral mechanisms is likely secondary to an 
underlying disease process: most notably 
intra-thoracic or intra-abdominal neoplasia.
• Predominantly affects the diaphyseal region 
of phalanges, metacarpals, and metatarsals.
• More common in dogs than cats.
• Age of highest frequency >8 years; coincides 
with the peak incidence of neoplasia.
SIGNS
• Chronic or acute lameness with pain in one 
or more limbs.
• Reluctance to move or use affected limb(s).
• Large firm swelling of affected limb(s).
• Respiratory clinical signs if intra-thoracic 
disease present (rare).
• Long bone or distal extremities—enlarged, 
firm, taut, thickened; not edematous.
• Single or multiple limbs.
• Firm swelling may extend proximally with 
progression of disease.
• Lameness and pain noted in affected 
limb(s).
• Primary and metastatic neoplasia—lung 
tumors; esophageal sarcoma; rhabdomyo -
sarcoma; adenocarcinoma of the adrenal 
gland, liver, or prostate; nephroblastoma; 
renal cell carcinoma; thoracic and abdominal 
mesotheliomas.
• Non-neoplastic conditions—pneumonia, 
lung abscess/granulomas, dirofilariasis; 
congenital or acquired heart disease, bronchial 
foreign bodies; Spirocerca lupi  infestation of 
the esophagus; focal lung atelectasis; obscure 
toxins; hypertension; hyperestrogenism; 
congenital idiopathic megaesophagus.
  DIAGNOSIS
• Osteomyelitis—asymmetric; edematous; 
lytic bone lesions; history of penetrating 
trauma or systemic infection.
• Metastatic neoplasia—asymmetric.
• Hypervitaminosis A (feline)—asymmetric; 
generally involves joint surface.• Hypertrophic osteodystrophy—metaphy-
seal abnormality, young dogs.
• Multiple cartilaginous exostosis—metaphy-
• Degenerative joint disease—involves 
articular surface changes in multiple joints.
Dependent on underlying cause and 
Fecal examination—rule out gastrointestinal 
and respiratory parasitism.
IMAGING
• Radiographs of affected long bones—
bilaterally symmetric extensive, aggressive, or 
nonaggressive periosteal new bone formation 
on diaphysis; palisading periosteal reaction; 
joints not affected.
(radiographs, ultrasound, and/or CT)—
identify and differentiate primary lesions.
fungal)—in atypical cases to rule out 
neoplasia and osteomyelitis.
  TREATMENT
• Directed at managing, treating, or removing 
the underlying cause.
• Options in selected cases—unilateral 
vagotomy on the side of a lung lesion or 
bilateral cervical vagotomy; incising through 
parietal pleura; subperiosteal rib resection.
• Dictated by underlying cause.
• Analgesics/anti-inflammatories—as needed.
• No known clinically proven benefit for 
steroid therapy.
  FOLLOW-UP
Condition indicates other disease processes—
identify the primary cause.
• Clinical signs and bone changes may resolve 
with treatment of underlying disease.
• Bone changes may take several months to 
regress.
• Prognosis—guarded to poor due to the 
common occurrence of neoplastic causes; 
non-neoplastic lesions may resolve with 
appropriate treatment of primary cause.• T umor recurrence or metastasis may result 
in recurrence of osteopathy.
• No relationship between size, site, or 
histologic type of primary lesion, the 
development of or recurrence of hypertrophic 
osteopathy postoperatively.
SYNONYMS
• Hypertrophic pulmonary osteopathy/
osteoarthropathy (HPO/HPOA).
• Hypertrophic osteoarthropathy (HOA).
2006, 171(2):308–313.
Dunn ME, Blond L, Letard D, Difruscia R. 
Hypertrophic osteopathy associated with 
infective endocarditis in an adult boxer dog. 
J Small Anim Pract 2007, 48(2):99–103.
Foster SF . Idiopathic hypertrophic osteopathy 
in a cat. J Feline Med Surg 2007, 
9(2):172–173.
Huang C-H, Jeng C-R, Lin C-T, Yeh L-S. 
Feline hypertrophic osteopathy: a collection 
of seven cases in Taiwan. JAAHA 2010, 
46:346–352.
Liptak JM, Monnet E, Dernell WS, Withrow 
SJ. Pulmonary metastatectomy in the 
management of four dogs with hypertrophic 
osteopathy. Vet Comp Onc 2004, 
2(1):1–12.

714  Blackwell’s Five-Minute Veterinary Consult  
HHypertrophic Pyloric Gastropathy, Chronic
  BASICS
Pyloric stenosis or chronic hypertrophic 
pyloric gastropathy is an obstructive 
narrowing of the pyloric canal resulting from 
varying degrees of muscular hypertrophy or 
mucosal hyperplasia.
• Can result from a congenital lesion 
composed primarily of hypertrophy of the 
smooth muscle or be one of three types of 
acquired form—primarily circular muscle 
hypertrophy (type 1), a combination of 
muscular hypertrophy and mucosal 
hyperplasia (type 2), or primarily mucosal 
hyperplasia (type 3).
• The cause is unknown; proposed factors 
include increased gastrin concentrations 
(which have a trophic effect on the muscle 
and mucosa) or changes in the myenteric 
plexus that lead to chronic antral distension 
and its associated effects.
• Gastrointestinal (GI)—chronic intermittent 
vomiting; regurgitation has also been reported.
• Musculoskeletal—weight loss.
• Respiratory—possible aspiration 
GENETICS
Inheritance pattern unknown.
Uncommon
N/A
Species
• More common in the dog.
• Rare in the cat.
• Congenital—brachycephalic breeds (boxer, 
Boston terrier, bulldog); Siamese cats.
• Acquired—Lhasa apso, shih tzu, Pekingese, 
poodle.
• Congenital—shortly after weaning 
(introduction of solid food) and up to 1 year 
of age.
• Acquired—typically middle-aged to older 
(average 9.8 years of age).
T wice as many males as females.
SIGNS
• Clinical signs are related to the degree of 
pyloric narrowing.
• Projectile vomiting is generally not a 
presenting complaint.Historical Findings
• Chronic intermittent vomiting of 
undigested or partially digested food (rarely 
containing bile), often several hours after 
eating.
• Congenital lesions associated with clinical 
signs shortly after weaning.
• Frequency of vomiting increases with time.
• Lack of response to antiemetic agents or 
motility modifying agents.
• Occasional anorexia with weight loss.
Most dogs are generally in good physical 
CAUSES
• Congenital or acquired.
• May be influenced by infiltrative mural 
diseases.
• Chronic elevations in gastrin concentra-
tions may play a role.
• Neuroendocrine factors may play a role.
Chronic stress, inflammatory disorders, 
chronic gastritis, gastric ulcers, and genetic 
predispositions influence the disease process in 
humans and may play a role in small animals.
  DIAGNOSIS
• Gastric neoplasia.
• Gastric foreign body.
• Granulomatous infectious disease (e.g., 
pythiosis).
• Motility disorders.
• Cranial abdominal mass—pancreatic or 
duodenal.
• Findings vary, depending on degree and 
chronicity of obstruction.
• Hypochloremic metabolic alkalosis (character -
istic of pyloric outflow obstruction), metabolic 
acidosis, or mixed acid-base imbalance.
• Anemia—if concurrent GI ulceration.
• Prerenal azotemia—if dehydration present.
N/A
IMAGING
Abdominal Radiographs
Normal to markedly distended stomach.
Upper GI Barium Contrast Study
• May display a “beak” sign created by pyloric 
narrowing, allowing minimal barium to pass 
into the pyloric antrum.
• Retention of most of the barium in the 
stomach after 6 hours indicates delayed 
gastric emptying.• Intraluminal filling defects or pyloric wall 
thickening.
Fluoroscopic Barium Contrast Study
• Normal gastric contractility.
• Delayed passage of barium through the 
pylorus.
Measurable thickening of the wall of the 
pylorus and antrum.
Endoscopy—allows evaluation of the mucosa 
for ulceration, hyperplasia, and mass lesions; 
specimens can be obtained for histopatho-
logic evaluation.
• Include focal to multifocal mucosal polyps, 
diffuse mucosal thickening, and pyloric wall 
thickening, with variable degree of pyloric 
• Changes range from hypertrophy of the 
circular smooth muscle to hyperplasia of the 
mucosa and associated glandular structures; a 
wide spectrum of inflammatory cell 
infiltration exists.
  TREATMENT
• Depends on severity of clinical signs.
• Patients should be evaluated and surgery 
scheduled at the earliest convenience.
• Appropriate parenteral fluids to correct any 
electrolyte imbalances and metabolic alkalosis 
or acidosis.
• Isotonic saline (with potassium supplemen-
tation) is the fluid of choice for hypochlo-
remic metabolic alkalosis.
• Consideration of postoperative nutritional 
support is important.
• In severe cases treated with gastroduodeno -
stomy or gastrojejunostomy, surgical 
placement of a jejunostomy tube for enteral 
nutrition may be advantageous.
ACTIVITY
Restrict as needed.
DIET
Highly digestible, low fat—until surgical 
intervention is feasible.
• Surgical treatment is highly successful.
• If clinical signs recur postoperatively, more 
aggressive surgical procedures may be indicated.
• Surgical intervention is the treatment of 
choice.
• Goals involve establishing a diagnosis with 
histopathologic samples, excising abnormal 
tissue, and restoring GI function with the 
least invasive procedure.

Canine and Feline, Seventh Edition  715
H• Surgical procedures depend on the extent of 
obstruction—pyloromyotomy (Fredet- 
Ramstedt), pyloroplasty (Heineke-Mikulicz or 
antral advancement flap), gastroduodenostomy 
(Billroth 1), gastrojejunostomy (Billroth 2).
• Antiemetics and motility modifiers are 
generally ineffective.
• H2 antagonists and proton pump inhibitors 
may provide symptomatic relief.
• Evidence of complete pyloric obstruction 
precludes the use of promotility drugs.
• Avoid anticholinergic agents because of 
their inhibitory effects on GI motility.
N/A
N/A
Postoperatively for recurrence of clinical signs 
because of poor choice of surgical procedure.
N/A
Postoperative surgical complications include 
recurrence of clinical signs, gastric ulceration, 
pancreatitis, bile duct obstruction, and 
incisional dehiscence with peritonitis.
• 85% of dogs show good to excellent results 
with resolution of clinical signs on proper 
• Poor prognosis if gastric neoplasia (especially 
adenocarcinoma) is an underlying cause.
Gastric ulceration.AGE-RELATED FACTORS
Intermittent vomiting in young brachyce-
phalic breeds on weaning is suggestive of 
congenital stenosis.
None
High gastrin concentrations in pregnant females 
may predispose to development of the syndrome.
SYNONYMS
• Chronic hypertrophic antral gastropathy.
• Hypertrophic gastritis.
• Antral pyloric hypertrophy.
• Congenital pyloric stenosis.
Bellenger CR, Maddison JE, Macpherson 
GC, Ilkiw JE. Chronic hypertrophic pyloric 
gastropathy in 14 dogs. Aust Vet J 1990, 
67:317–320.
Radlinsky M, Fossum TW. Surgery of the 
digestive system. In: Fossum TW, ed., Small 
Animal Surgery, 5th ed. Philadelphia, PA: 
Elsevier, 2019, pp. 425–427.
Consulting Editor  Mark P . Rondeau(continued)  Hypertrophic Pyloric Gastropathy, Chronic

716  Blackwell’s Five-Minute Veterinary Consult  
HHyperviscosity Syndrome
  BASICS
OVERVIEW
• An assortment of clinical signs caused by 
high blood viscosity.
• Typically results from markedly high 
concentration of plasma proteins, although 
can result (rarely) from extremely high 
erythrocyte or leukocyte counts.
• Most frequently seen as paraneoplastic 
syndrome, often associated with multiple 
myeloma or other lymphoid neoplasms.
• Total plasma protein may exceed 10 g/dL 
(100 g/L), with serum protein electrophoresis 
showing monoclonal gammopathy or rarely 
biclonal gammopathy.
• Clinical signs caused by reduced blood flow 
through smaller vessels, high plasma volume, 
and associated coagulopathy.
• Systems affected include hemic/lymphatic/
immune, ophthalmic, and nervous; in rare 
cases, pulmonary thromboembolism may 
occur.
• Dogs more frequently affected than cats.
• No sex or breed predilections.
• More common in older animals due to 
increased incidence of malignancy.
SIGNS
• No consistent signs.
• Blindness, ataxia, seizures, syncope.
• Congestive heart failure.
• Neurologic deficits, including seizures and 
disorientation.
• Tachycardia and tachypnea due to volume 
overload (e.g., congestive heart failure) or 
• Epistaxis or other mucosal bleeding.
• Hepatomegaly, splenomegaly, lympha  - 
denopathy.
• Visual deficits associated with engorged 
retinal vessels, retinal hemorrhage or 
detachment, and papilledema.
• Multiple myeloma and plasma cell tumors—
immunoglobulin (Ig) M > IgA > IgG.
• Lymphocytic leukemia or lymphoma.
• Marked polycythemia—hematocrit (HCT) 
>65%, usually >75%.
• Chronic atypical inflammation with 
monoclonal gammopathy (e.g., ehrlichiosis or 
leishmaniasis in dogs).• Chronic autoimmune disease (e.g., systemic 
lupus erythematosus and rheumatoid 
arthritis)—very rare.
  DIAGNOSIS
• Other unexplained neurologic disease or 
• Hyperviscosity is a syndrome, not a final 
• Nonregenerative anemia (in patients 
without erythrocytosis as a cause of 
hyperviscosity), thrombocytopenia, or 
• Hyperproteinemia (total plasma protein  
>9 g/dL; 90 g/L) and hyperglobulinemia  
(>5 g/dL; 50 gm/L).
• Azotemia and hypercalcemia, if hyperviscosity 
caused by paraneoplastic syndrome.
• Isosthenuria and marked proteinuria.
• High concentration of IgG, IgA, or IgM, as 
detected by radial immunodiffusion.
• High plasma or serum viscosity (>3× greater 
than water).
• Prolonged prothrombin time or activated 
partial thromboplastin time, abnormal 
platelet function testing.
• Other testing as indicated by primary disease.
• Bence-Jones proteinuria in patients with 
IMAGING
Hepatosplenomegaly, cardiomegaly, and 
osteolytic lesions (in association with multiple 
myeloma) are possible.
Bone marrow aspirate or core biopsy—plasma 
cell or lymphoid infiltrate.
  TREATMENT
• Generally treat as inpatient.
• T reat underlying disease.
• Phlebotomy (15–20 mL/kg) with isotonic 
crystalloid fluid volume replacement.
• Plasmapheresis, either manual or automated.
As dictated by underlying disease.
Provide treatment for underlying neoplastic 
or inflammatory condition.CONTRAINDICATIONS/POSSIBLE 
• Avoid use of medications that might 
increase vascular volume, including synthetic 
colloids (e.g., hetastarch); do not try to 
correct compensatory low albumin.
• Avoid medications that alter platelet 
function.
  FOLLOW-UP
• Monitor serum or plasma proteins 
frequently as marker of treatment efficacy.
• CBC, biochemistry panel, and urinalysis to 
monitor other laboratory abnormalities.
SEE ALSO
• Ehrlichiosis and Anaplasmosis.
• Erythrocytosis.
• Leukemia, Chronic Lymphocytic.
• Multiple Myeloma.
• Plasmacytoma, Mucocutaneous.
Hohenhaus AE. Syndromes of 
hyperglobulinemia: diagnosis and 
therapy. In: Kirk RW, ed., Current 
Veterinary Therapy XII. Philadelphia, 
PA: Saunders, 1995, pp. 523–530.

Canine and Feline, Seventh Edition  717
HHyphema
  BASICS
Blood inside the anterior chamber in the 
form of a blood clot, settled blood in the 
ventral anterior chamber, or red blood cells 
suspended throughout the aqueous.
• Breakdown of the blood–aqueous barrier and/
or direct injury to the iris and ciliary body blood 
vessels; causes include direct trauma to the 
cornea or anterior uvea (iris and ciliary body), 
inflammation, and damage to blood vessel walls 
(e.g., caused by systemic hypertension, antigen-  
antibody complexes, or circulating infectious 
organisms or neoplastic cells).
• Abnormal hemostasis due to a coagulopathy 
or thrombocytopenia.
• Bleeding from abnormal vessels within the 
eye; this is most commonly due to pre-iridal 
fibrovascular membranes (PIFMs), which 
form in response to chronic intraocular disease 
(uveitis, retinal detachment, glaucoma, 
neoplasia); rarely, abnormal congenital blood 
vessels in the eye such as persistent pupillary 
membranes, tunica vasculosa lentis, or hyaloid 
artery may bleed, causing hyphema.
Not uncommon ophthalmic finding and one 
that is important to recognize, as it may be 
the presenting clinical sign for serious 
underlying systemic disease.
Species
Collies with collie eye anomaly.SIGNS
Historical Findings—Primary Ophthalmic 
Causes
• Usually a unilateral presentation in an 
otherwise systemically normal patient.
• Blunt globe trauma will often have a 
compatible history.
• Corneal perforation may have a history of a 
corneal ulcer, or preceding encounter with a 
cat resulting in a cat claw laceration, 
especially in puppies.
Historical Findings—Systemic Causes
• Unilateral or bilateral presentation; bilateral 
presentation is strongly supportive of systemic 
etiology.
• Weight loss, anorexia, lethargy, decreased 
vision, or loss of vision may accompany some 
systemic causes.
• Ocular pain usually accompanies infectious 
and neoplastic causes due to accompanying 
uveitis.
Physical Examination Findings—Primary 
Ophthalmic Causes
• Except in cases of generalized trauma, the 
physical exam will be unremarkable with 
abnormalities restricted to the globe and 
periorbital soft tissues.
• Blunt trauma patients will have painful 
periorbital soft tissue swelling and 
uncommonly orbital rim fractures; there is 
often total hyphema obscuring other 
intraocular structures.
• Perforating trauma is associated with severe 
pain, a bloody or clear (aqueous) ocular 
discharge, varying degrees of hyphema, miosis, 
and anterior synechia, and a shallow anterior 
chamber; corneal edema will surround the 
perforation site and an iris prolapse may be 
present through the perforation.
• Hyphema due to PIFMs, retinal 
detachment, neoplasia, or congenital 
vasculature is usually nonpainful with very little intraocular inflammation (absent 
aqueous flare, miosis).
• Hypermature cataract supports the 
development of either PIFM or retinal 
detachment as a cause of hyphema.
Physical Examination Findings—
Systemic Disease Causes
• Ophthalmic examination findings will 
vary depending on the etiology of the 
hyphema.
• When an underlying systemic disease is 
suspected, a thorough physical exam is 
warranted; the exam may be unremarkable or 
have significant findings such as lymphadeno -
pathy, fever, or petechiae.
• Hyphema due to noninflammatory etiologies 
such as hypertension, thrombocytopenia, and 
coagulopathies will usually manifest minimal 
discomfort and uveitis (trace or no aqueous 
flare, no miosis, no conjunctival hyperemia); 
hypertension is almost always associated with 
retinal involvement such as retinal hemorrhages 
and/or retinal detachment.
• Patients with coagulopathies may have 
bleeding elsewhere, including the subconjunc -
tival tissue and retrobulbar space; thrombocy -
topenia may create petechia on the palpebral 
or nictitans conjunctiva.
• Infectious and neoplastic etiologies often 
cause significant pain, anterior uveitis (miosis, 
aqueous flare, fibrin, iridal hyperemia and 
swelling), chorioretinitis with retinal 
detachment, and possible secondary 
glaucoma.
CAUSES
• Ophthalmic—hypermature cataract, retinal 
detachment, chronic anterior uveitis.
• Systemic—any disease or disorder 
predisposing to the systemic diseases known 
to cause uveitis or direct vascular damage 
Table 1
Causes of hyphema.
Primary Ophthalmic Etiologies Systemic Disease Etiologies
Trauma (blunt or perforating) Hypertension
Extraocular vascular compression (choking, chest compression) Hyperviscosity syndrome
PIFM Thrombocytopenia
Retinal detachment Coagulopathy
Primary intraocular neoplasia (iris melanoma, ciliary body  
adenoma/adenocarcinoma)Metastatic neoplasia (especially lymphoma)
Golden retriever pigmentary uveitis Rickettsial disease
Patent anomalous congenital blood vessels (persistent pupillary  
membranes, tunica vasculosa lentis, hyaloid artery)FIP
Fungal disease
Prototheca
Parasitic (aberrant intraocular larval migration)

718  Blackwell’s Five-Minute Veterinary Consult  
H(e.g., chronic renal disease, hyperthyroidism, 
systemic hypertension); living in geographic 
areas with endemic tick-borne disease.
  DIAGNOSIS
Deep corneal vascularization, along the 
ventral limbus, can be mistaken for 
hyphema.
Abnormal findings may help support a 
diagnosis of systemic disease.
Based on history and physical examination 
findings, coagulation profile and serology 
(rickettsial, fungal) may be indicated if 
systemic disease is suspected.
IMAGING
• Ocular ultrasound is indicated to evaluate 
for retinal detachment or uveal tumors when 
not visible on the ophthalmic examination.
• Based on history and physical exam -
ination findings, thoracic radiographs, 
abdominal radiographs, and abdominal 
ultrasound may be indicated if systemic 
disease is suspected.
• Systemic arterial blood pressure 
measurement using Doppler ultrasonic flow 
probe or oscillometric techniques, if 
hypertension is suspected.
• Lymph node aspirates if lymphadenopathy 
is present or if neoplasia or fungal disease is 
Gross hemorrhage in the anterior chamber.
  TREATMENT
Outpatient medical care is appropriate unless 
an underlying systemic disease is identified 
that requires hospitalization.
ACTIVITY
No restricted activity is required unless the 
patient is blind (restrict environment to 
fenced yards, no in-ground pools, leash walks, 
etc.) or the hyphema is due to thrombocyto-
penia or coagulopathy (avoid rough play, 
unrestricted running, etc.).
• Hyphema itself, although it appears 
dramatic, is not painful.
• It is very important to identify the 
underlying cause of the hyphema, as some etiologies pose a serious health threat.
• Ophthalmic treatment should be initiated 
immediately to try to prevent painful and 
sometimes irreversible and blinding sequelae 
like glaucoma.
• Hyphema secondary to a perforating 
corneal laceration or ulceration should be 
surgically repaired by direct suturing of the 
cornea (laceration) or corneal graft (perforated 
ulcer) when a visual outcome is expected; for 
a severe perforation with extensive iris 
prolapse and loss of the pupil, enucleation is 
• Permanently blind and painful eyes should 
be enucleated (with histopathology) for 
permanent comfort.
• Surgical irrigation/removal of the hyphema 
is not successful, as the trauma of the surgery 
results in exacerbation of the hyphema and 
intraocular inflammation.
• Topical prednisolone acetate 1% or 
dexamethasone 0.1% q4–8h to help stabilize 
the blood–aqueous barrier; do not use if a 
corneal ulcer or perforation is present .
• Atropine 1% q6–24h to help prevent 
posterior synechia; atropine is contraindicated 
if secondary glaucoma is present .
• Systemic nonsteroidal anti-inflammatory 
drug (NSAID—carprofen, meloxicam, 
deracoxib) for analgesia in patients with 
perforating trauma; may help stabilize 
blood–aqueous barrier.
• Systemic prednisone/prednisolone with 
known or suspected choroidal/retinal 
involvement, depending on the underlying 
cause ; anti-inflammatory dose (0.5–1.0 mg/kg 
PO q24h) can be used for blunt trauma, 
feline infectious peritonitis (FIP), and 
rickettsial and fungal disease with proper 
antimicrobial therapy.
• Topical carbonic anhydrase inhibitors 
(dorzolamide 2%, brinzolamide 1%, q8h), 
beta blocker (timolol 0.5% q8–12h), and/or 
sympathomimetic (dipivefrin 0.1% q8–12h) 
can be used if secondary glaucoma is present.
• Topical NSAIDs (flurbiprofen, diclofenac, 
ketorolac, etc.) are generally considered 
contraindicated with hyphema.
• Topical prostaglandin analogues 
(latanoprost, travoprost, bimatoprost) are 
contraindicated in secondary glaucomas.  FOLLOW-UP
• Tonometry should be used to monitor for 
secondary glaucoma, which lowers the 
prognosis for a visual outcome.
• Perform tonometry every 1–2 days if the 
intraocular pressure (IOP) is high normal or 
greater, or if risk factors such as fibrin and/or 
posterior synechia are present.
• Perform tonometry weekly if the IOP is 
low, or if the hyphema and anterior uveitis are 
mild to moderate in severity.
• Tonometry is contraindicated with a corneal 
perforation .
Secondary glaucoma, posterior synechia/
dyscoria, cataract formation, loss of vision, 
possible loss of the eye if the eye becomes 
permanently blind and painful.
• If the underlying cause of the hyphema can 
be successfully treated, such as repair of a 
corneal laceration or control of hypertension, 
and intraocular damage is not extensive, the 
prognosis is good for complete resolution of 
the hyphema.
• If trauma to the eye is severe or if the 
underlying disease is not controlled, the 
hyphema will persist and blindness can result; 
no improvement in hyphema after 2 weeks 
following blunt trauma has a poor prognosis 
for return of vision; enucleation should be 
performed in any cat with permanent 
blindness from trauma due to the risk of 
developing traumatic ocular sarcoma.
• Hyphema caused by bleeding from PIFMs 
usually does not resolve or will resolve and recur.
• If the eye is painful due to a perforated 
globe or secondary glaucoma, with no 
reasonable hope of regaining vision, 
enucleation is recommended.
drug.
• PIFM = pre-iridal fibrovascular membrane.
Consulting Editor  Kathern E. MyrnaHyphema  (continued)

Canine and Feline, Seventh Edition  719
HHypoadrenocorticism (Addison’s Disease)
  BASICS
• Endocrine disorder resulting from deficient 
production of glucocorticoids and, usually, 
mineralocorticoids.
• Primary hypoadrenocorticism (Addison’s 
disease) is due to destruction of the adrenal 
cortices resulting in glucocorticoid and 
mineralocorticoid deficiency.
• The term atypical hypoadrenocorticism has 
been applied to the subset of dogs with 
primary hypoadrenocorticism and normal 
• Secondary hypoadrenocorticism results 
from pituitary adrenocorticotropic hormone 
(ACTH) insufficiency, resulting in inadequate 
glucocorticoid production by the adrenal 
cortices.
• Mineralocorticoid (aldosterone) deficiency 
results in a diminished ability to excrete 
potassium and retain sodium, disrupting 
sodium and potassium balance in the body.
• Sodium loss leads to diminished effective 
circulating volume; this contributes to 
pathophysiologic changes and clinical 
abnormalities, including prerenal azotemia, 
hypotension, dehydration, weakness, and 
• Hyperkalemia can result in weakness, 
lethargy, and anorexia; it may result in 
bradyarryhthmias.
• Glucocorticoid (cortisol) deficiency 
contributes to anorexia, vomiting, diarrhea, 
melena, lethargy, and weight loss; due to its 
role in glucose homeostasis, hypocortisolemia 
predisposes to hypoglycemia.
GENETICS
A genetic basis has been determined in 
standard poodles, bearded collies, Nova 
Scotia duck tolling retrievers, and 
Leonbergers.
Unknown; considered uncommon in dogs 
and very rare in cats.
Species
• Great Danes, Rottweilers, Portuguese water 
dogs, standard poodles, bearded collies, 
Leonbergers, West Highland white terriers, 
Novia Scotia duck tolling retrievers and soft 
coated wheaten terriers have increased relative risk; golden retrievers and Chihuahuas have 
decreased relative risk.
• No predilection in cats.
• Dogs—range: <1 to >12 years; median: 
4 years; young to middle-aged.
• Cats—range: 1–9 years; middle-aged.
Female dogs at increased relative risk; no 
predilection in cats.
SIGNS
• Signs vary from mild in patients with 
chronic hypoadrenocorticism to severe and 
life-threatening in an acute Addisonian crisis.
• Multiple organ systems may be involved; 
type and extent of involvement vary with case.
• Dogs—lethargy, anorexia, vomiting, 
weakness, weight loss, diarrhea, waxing/
waning course, previous response to therapy, 
polyuria/polydipsia (PU/PD), melena.
• Cats—lethargy, anorexia, weight loss, 
vomiting, waxing/waning course, previous 
response to therapy, PU/PD.
• Dogs—depression, weakness, hypovolemia, 
dehydration, collapse, hypothermia, melena, 
hypotension, bradycardia, painful abdomen, 
hair loss.
• Cats—dehydration, hypovolemia, 
weakness, hypothermia, depression, 
hypotension, bradycardia, collapse.
CAUSES
• Primary hypoadrenocorticism—idiopathic 
(immune-mediated), mitotane or trilostane 
overdose, granulomatous disease, metastatic 
tumors, fungal disease, coagulopathy, adrenal 
hemorrhage or necrosis.
• Secondary hypoadrenocorticism—
iatrogenic following withdrawal of long-term 
glucocorticoid administration, ACTH 
deficiency, panhypopituitarism, pituitary or 
N/A
  DIAGNOSIS
• Signs are nonspecific and often mimic 
gastrointestinal and renal diseases; differential 
diagnoses for gastrointestinal distress include 
intestinal obstruction (e.g., foreign body, 
intussusception, neoplasia), gastrointestinal 
perforation, pancreatitis, infectious disease, 
and others (see Acute Vomiting).
• Differential diagnoses for hyperkalemia 
include acute kidney injury, urinary tract 
obstruction, third-space fluid loss (e.g., peritoneal or pleural effusion, uroabdomen), 
and T richuriasis.
• Although no signs are pathognomonic, a 
waxing and waning course and previous 
response to nonspecific medical intervention 
should alert the clinician.
• Hematologic abnormalities may include 
anemia, eosinophilia, and lymphocytosis.
• The absence of a stress leukogram in a sick 
patient should prompt consideration of 
• Serum biochemical findings may include 
hyperkalemia, azotemia, hyponatremia, hypo -
chloremia, hyperphosphatemia, hypercalcemia, 
hypoalbuminemia, increased alanine amino -
transferase (ALT) activity, and hypoglycemia.
• Urinalysis often reveals impaired urine-
concentrating ability and in some cases 
isothenuria; some patients with isothenuria 
are also azotemic, potentially causing 
confusion with primary renal disease.
• Some patients with hypoadrenocorticism 
exhibit normal electrolyte levels (so-called 
atypical hypoadrenocorticism).
• Definitive diagnosis is by demonstration of 
undetectable to low (<2  μg/dL) baseline 
serum cortisol concentrations that fail to 
increase above 2  μg/dL following ACTH 
• Cortisol concentrations should be measured 
before and 1 hour after administration of 
synthetic ACTH (1  μg/kg, IV in dogs and  
5 μg/kg, IV in cats).
• The ACTH stimulation test can be 
performed during initial stabilization and 
treatment if dexamethasone is used (does not 
cross-react with the cortisol assay).
• If prednisone, prednisolone, or hydrocorti -
sone has been administered, the treatment 
must be discontinued, and the ACTH 
stimulation test performed at least 24 hours 
after changing the glucocorticoid to dexameth -
asone (do not withhold corticosteroids from a 
patient in acute crisis).
• A low resting cortisol does not confirm 
hypoadrenocorticism; an ACTH stimulation 
test is required.
• Plasma ACTH concentration can be 
measured in patients with normal electrolyte 
concentrations to differentiate primary from 
secondary hypoadrenocorticism; must collect 
sample before initiating therapy, especially 
glucocorticoids; carefully follow sample 
handling instructions from the laboratory; 
plasma ACTH concentrations are high with 
primary hypoadrenocorticism and undetectable 
to low with secondary hypoadrenocorticism.
IMAGING
• Radiographs may reveal microcardia, 
narrowed vena cava or descending aorta, 
hypoperfused lung fields, less commonly 
microhepatica, and very rarely megaesophagus.

720  Blackwell’s Five-Minute Veterinary Consult  
H• Abdominal ultrasound may reveal small 
adrenal glands.
• Imaging is not usually necessary for 
diagnosis, but is often performed during the 
diagnostic workup in patients with gastro -
intestinal signs.
• Gross examination—atrophy of the adrenal 
glands.
• Microscopically—lymphocytic-plasmocytic 
adrenalitis and/or adrenocortical atrophy; 
other abnormalities may be present 
depending on etiology (neoplasia, fungal 
disease, etc.).
  TREATMENT
• An acute Addisonian crisis is a medical 
emergency requiring intensive therapy and 
24-hour observation and care; the diagnostic 
workup is performed while initial treatment 
and stabilization are ongoing; cats often 
respond more slowly than dogs.
• The intensity of treatment for patients with 
chronic hypoadrenocorticism depends on the 
severity of clinical signs; usually initial 
stabilization and therapy are conducted on an 
inpatient basis.
• T reat acute Addisonian crisis with rapid 
correction of hypovolemia and restoration 
of volume status using isotonic fluids, 
preferably Plasma-Lyte® or lactated Ringer’s 
solution; although normal saline (0.9% 
NaCl) was historically recommended, it can 
exacerbate existing acidosis, but can be used 
in the absence of other isotonic crystalloid 
fluids.
• Do not increase sodium concentration by 
more than 12 mEq/L every 24 hours to 
prevent CNS myelinolysis; this is more 
likely to occur when the initial sodium 
concentration is <120 mEq/L; lactated 
Ringer’s solution has a sodium content of 
130 mEq/L and will increase the sodium 
concentration more slowly than Plasma-
Lyte (140 mEq/L) and 0.9% saline 
(154 mEq/L).
• Although most cases respond to fluid 
resuscitation alone, severe hyperkalemia 
(>8.5–9.0 mEq/L and/or bradycardia or other 
ECG abnormalities) may require additional 
therapy; see Hyperkalemia.
• If necessary, a colloid fluid also can be given 
to treat hypotension and hypovolemia.
• T reat hypoglycemia, if present, with IV 
dextrose; due to hyperosmolarity, 50% 
dextrose should be diluted a minimum of 
1 : 3 prior to IV administration.
• Monitor hydration status, blood pressure, 
urine output, rectal temperature, and heart 
rate and rhythm.ACTIVITY
Avoid unnecessary stress and exertion during 
an Addisonian crisis.
DIET
No need to alter.
• Lifelong glucocorticoid and/or 
mineralocorticoid replacement therapy is 
required.
• Increased dosages of glucocorticoid (above 
maintenance requirements) are required 
during periods of stress such as travel, 
boarding, hospitalization, and surgery.
• In an Addisonian crisis, parenteral admini -
stration of a rapidly acting glucocorticoid such 
as dexamethasone sodium phosphate is 
indicated; dexamethasone sodium phosphate is 
given at a dose of 0.25 mg/kg IV on the first 
day, and 0.15 mg/kg on the second day; 
glucocorticoid is gradually tapered and 
changed to oral prednisone or prednisolone as 
the condition improves.
• Alternatively, hydrocortisone (0.5–
0.625 mg/kg/h) has both mineralocorticoid 
and glucocorticoid properties, and 
prednisolone sodium succinate (2 mg/kg IV 
initially, and then 0.5 mg/kg IV q12h) is also 
an option; since both of these cross-react with 
cortisol assays (dexamethasone does not), they 
should be administered after the ACTH 
stimulation test is complete, or ACTH 
stimulation testing should be delayed at least 
24 hours after administration.
• During an Addisonian crisis, supportive 
therapy, including gastroprotectants and 
anti-emetics, is often necessary.
• Chronic primary hypoadrenocorticism—
most patients will need daily glucocorticoid 
replacement (prednisone 0.1–0.2 mg/kg/day 
PO), as well as mineralocorticoid replacement 
(desoxycorticosterone [DOCP], 2.2 mg/kg 
IM/SC, typically given monthly and adjusted 
as needed on the basis of serial electrolyte 
determinations); the initial monthly DOCP 
dose for an average-sized cat is 12.5 mg IM/
SC; though not preferred, an alternative means 
of administering glucocorticoid replacement to 
cats is Depo-Medrol® (10 mg IM monthly).
• Prednisone dose is adjusted based on clinical 
signs and side effects; the dose is decreased if 
PU/PD, polyphagia, and muscle wasting are 
present, but increased if vomiting, diarrhea, or 
lethargy occurs; some dogs, particularly large 
breeds, require less than 0.1 mg/kg/day, but all 
dogs with hypoadrenocorticism require some 
prednisone, but all dogs with hypoadreno -
corticism require some glucocorticoid.
• The label dose of DOCP is 2.2 mg/kg, but 
this author routinely begins at 1.5 mg/kg with owner consent to use an off-label dose.
• Alternatively, an oral mineralocorticoid 
replacement can be used (fludrocortisone 
acetate 5–10  μg/kg PO q12h, adjusted by 
0.05–0.1 mg increments on the basis of serial 
electrolyte determinations); fludrocortisone 
has some glucocorticoid activity and the 
maintenance dose of prednisone for patients 
receiving fludrocortisone may be lower than 
for dogs receiving DOCP; a few dogs develop 
PU/PD and/or polyphagia from 
fludrocortisone.
• Patients with confirmed atypical and 
secondary hypoadrenocorticism require only 
glucocorticoid supplementation (prednisone 
0.1–0.2 mg/kg/day PO), adjusted as 
described above.
N/A
See Hyperkalemia; Hyponatremia.
  FOLLOW-UP
• Depending on clinical presentation, 
patients hospitalized for treatment of 
hypoadrenocorticism may require intensive 
monitoring and frequent laboratory 
evaluations; monitor clinical status, urine 
output, CBC, blood chemistry, and ECG as 
needed; blood glucose and electrolytes may 
need to be evaluated several times daily 
during initial therapy; arterial or venous 
blood gas analysis may be of benefit.
• Monitor for melena, as some dogs 
experience severe gastrointestinal blood loss 
during and following a crisis, sometimes 
requiring blood transfusion.
• Measure electrolyte concentrations 2 and 4 
weeks following the first injection of DOCP , 
to determine whether the dose (2 weeks) and 
the dosing interval (4 weeks, prior to next 
injection) are appropriate; recheck electrolytes 
prior to next injection and each time the dose 
or dosing interval is adjusted; then check 
electrolyte concentrations every 6 months, or 
when the patient is sick.
• DOCP is usually required at monthly 
intervals; rare patients need injections as 
often as every 3 weeks; some dogs may 
require DOCP less than every 28–30 days; 
however, the author prefers to adjust the 
dose instead of extending the dosing 
interval, and does not decrease the dose (as 
directed below) and extend the dosing 
interval in the same dog.
• The majority of dogs with hypoadreno -
corticism will be well controlled on a 
maintenance DOCP dose of 1.5 mg/kg/
injection every month; if necessary based 
on expense, the DOCP dosage can be 
sequentially decreased by 10% each month Hypoadrenocorticism (Addison’s Disease)  (continued)

Canine and Feline, Seventh Edition  721
Hbased on electrolyte determinations, as 
some dogs can be controlled on a monthly 
dosage that is less than 1.5 mg/kg; make 
sure that the owner is aware that this is 
off-label use.
• Adjust the daily dose of fludrocortisone by 
0.05–0.1 mg increments as needed, based on 
serial electrolyte determinations; following 
initiation of therapy, check electrolyte levels 
weekly until they stabilize in the normal 
range; thereafter, check electrolyte 
concentrations monthly for the first 3–6 
months and then every 3–12 months.
• In many dogs given fludrocortisone, the 
daily dose required to control the disorder 
increases incrementally, usually during the 
first 6–24 months of therapy; in most dogs, 
the final fludrocortisone dosage needed is 
20–30  μg/kg/day PO; very few can be 
controlled on 10  μg/kg/day or less.
• In patients that were initially azotemic, 
monitor creatinine concentrations as needed 
following discharge from the hospital.
• Continue hormone replacement therapy for 
the lifetime of the patient.
• Increase the dosage of replacement 
glucocorticoid during periods of stress such as 
travel, boarding, hospitalization, and surgery.
• PU/PD may occur from prednisone 
administration, but this usually resolves with a 
decrease in dosage; rarely, it is necessary to try 
an alternative glucocorticoid, such as 
methylprednisolone, when the dog’s clinical 
signs are not controlled on a dose of prednisone 
that is low enough to eliminate side effects.• PU/PD may occur from fludrocortisone 
• Side effects from DOCP are uncommon; 
rarely weight gain and PU/PD are seen.
• Except for patients with primary hypoadreno -
corticism caused by granulomatous or 
metastatic disease and secondary hypoadreno -
corticism caused by a pituitary mass, the vast 
majority of patients have a good to excellent 
prognosis following proper stabilization, 
treatment, and monitoring.
• Owners must be reminded that they should 
not skip DOCP injections, as this could 
precipitate a potentially fatal, and inevitably 
costly, Addisonian crisis.
Concurrent endocrine gland failure occurs in 
up to 5% of dogs—hypothyroidism, diabetes 
mellitus, and/or hypoparathyroidism.
N/A
None
SYNONYMS
SEE ALSO
• Hyponatremia.ABBREVIATIONS
• DOCP = desoxycorticosterone.
Bates JA, Shott S, Schall WD. Lower initial 
dose desoxycorticosterone pivalate for 
treatment of canine primary 
hypoadrenocorticism. Aust Vet J 2013, 
91:77–82.
Lennon EM, Boyle TE, Hutchins RG, et al. 
Use of basal serum or plasma cortisol 
concentrations to rule out a diagnosis of 
hypoadrenocorticism in dogs: 123 cases 
(2000–2005). J Am Vet Med Assoc 2007, 
231:413.
Peterson ME, Kintzer PP , Kass PH. 
in dogs with hypoadrenocorticism: 225 cases 
(1979–1993). J Am Vet Med Assoc 1996, 
208:85–91.
Scott-Moncrieff JCR. Hypoadrenocorticism. In: 
St. Louis, MO: Elsevier, 2010, pp. 
1847–1757.
available online(continued)  Hypoadrenocorticism (Addison’s Disease)

722  Blackwell’s Five-Minute Veterinary Consult  
HHypoalbuminemia
  BASICS
Hypoalbuminemia defined as measured serum 
albumin value less than reference range.
• Albumin—constitutive protein exclusively 
synthesized in liver. • Provides 75–80% of 
plasma colloid oncotic pressure. • Low 
oncotic pressure due to serum albumin 
<1.5 g/dL permits fluid extravasation into 
interstitial and third-space compartments, 
causing edema and body cavity effusion.
Cardiovascular and respiratory—transudative 
effusions (pleural effusion, ascites); peripheral 
edema; pulmonary edema.
Accompanies many primary diseases that cause 
hepatic insufficiency, protein-losing enteropa -
thy (PLE), protein-losing nephropathy (PLN), 
hemorrhage, negative acute-phase response in 
chronic disease.
Species
Underlying disease may have breed 
Varies with syndrome association.
N/A
SIGNS
• Reflect primary disease leading to 
hypoalbuminemia. • Hypoalbuminemia 
influences metabolite and xenobiotic protein 
binding, plasma oncotic pressure, third-space 
fluid distribution, acid-base balance, and 
ability to maintain intravascular perfusion 
pressure.
• Vary with underlying disease. • Increased 
drug-related effects due to reduced protein 
binding.
• Vary with underlying primary disease.
• Serum albumin ≤1.5 g/dL often associated 
with pitting edema, decreased heart/lung 
sounds, and/or abdominal fluid wave.
CAUSES
Decreased Albumin Production
• Chronic hepatic insufficiency—chronic 
hepatitis; cirrhosis; idiopathic hepatic fibrosis; 
granulomatous hepatitis; congenital 
portosystemic shunt (PSS; dogs). • Inadequate nutritional intake/absorption 
(modest effect).
Extracorporeal Albumin Loss
• PLN—amyloidosis; glomerulonephritis. 
• PLE—lymphangiectasia; lymphoma; severe 
inflammatory bowel disease (IBD); histo -
plasmosis; pythiosis; chronic intussusception; 
Addison’s disease. • Severely exudative 
cutaneous lesions. • Chronic severe blood 
loss—usually enteric. • Repeated large-volume 
paracentesis of abdominal or pleural effusion.
Sequestration: Body Cavities/Tissues
• Inflammatory effusions—pancreatitis; 
septic or aseptic peritoneal or pleural 
effusions; chylous effusions (modest effect). 
• Vasculopathies—immune-mediated 
(systemic lupus erythematosus [SLE]); 
infectious (Ehrlichia, Rocky Mountain 
spotted fever); sepsis syndrome; other 
Downregulated albumin synthesis—
hyperglobulinemia, negative acute-phase 
response, negative nitrogen intake, catabolism 
• Diseases of the liver, kidney, intestines, and 
blood vessels.
• Negative nitrogen balance; poor nutrition.
  DIAGNOSIS
• Severe hepatic disease—may see 
jaundice; hepatic encephalopathy (HE); 
ascites. • PLE—diarrhea common but 
inconsistent. • Cutaneous lesions—must 
be severe and exudative (burns, toxic 
epidermal necrolysis [TEN], vasculitis, 
tumors, trauma). • External blood loss—
hemorrhage (enteric, urinary, other). 
• Malnutrition—mild hypoalbuminemia. 
• Aggressive fluid therapy—exacerbates 
low albumin.
CBC
• Depends on underlying disease. • Severe 
hepatic disease—red blood cell (RBC) 
microcytosis suggests PSS. • Severe blood 
loss—regenerative anemia or microcytic/
hypochromic anemia.
• Chronic hepatic disease—low albumin; 
normal to high globulin. • PLE—low 
albumin; variable globulin. • PLN—low 
albumin; globulin usually normal but may be 
low with severe PLN. • Exudative losses—low 
albumin; variable globulin. • Malnutrition—
low albumin; normal globulin. • Severe blood 
loss—low albumin; low to normal globulin. • Cholesterol—low with chronic hepatic 
disease, severe PLE, Addison’s disease, and 
severe malnutrition; high with PLN and 
pancreatitis. • Hepatic enzymes—alanine 
aminotransferase (ALT) may be high with 
chronic hepatitis, IBD causing PLE; high 
alkaline phosphatase (ALP) often seen with 
systemic inflammation as well as hepatic 
disease. • Bilirubin—sometimes high with 
hepatic disease. • Blood urea nitrogen 
(BUN)—often low with hepatic insufficiency 
or patients undergoing diuresis; high with 
reduced renal function or dehydration. 
• Hyperkalemia and hyponatremia—suggest 
hypoadrenocorticism, third-space effusions, or 
pseudohypoadrenocorticism (endoparasitism). 
• Spurious hypocalcemia—due to low protein.
• Rules out PLN and urologic blood loss. 
• Obtain urine by cystocentesis to avoid 
lower-tract contamination; caution : beware 
cystocentesis-induced microhematuria. 
• Proteinuria—confirm dipstick detection 
with chemical determination. • Urine 
protein : creatinine (UP : UCr) ratio— 
important; >3.0 compatible with nephrotic 
range proteinuria; must evaluate urine 
sediment: spurious positive values with active 
sediment (i.e., substantial pyuria, macroscopic 
hematuria, bacteriuria); many dogs with 
glomerulonephritis have hyaline, waxy, or 
granular casts; bacterial culture of urine 
necessary to rule out bacteriuria as cause of 
increased urine protein. • Microalbuminuria—
not helpful. • Ammonium biurate crystalluria—  
hepatic insufficiency, PSS, or acquired 
portosystemic shunt (APSS).
• Total serum bile acids (TSBA)—usually high 
with severe hepatic disease; sometimes spurious 
low values with PLE (fat malabsorption). 
• Physicochemical evaluation of effusion—
transudate (usually pure) if hypoalbuminemia 
is the major causal factor. • Antithrombin 
(AT)—may be low with PLE, PLN, and 
hepatic synthetic failure. • Protein C (PC)—  
may be low with severe hepatic disease/failure, 
PSS, sepsis.
IMAGING
• Thoracic radiography—pleural effusion; 
pulmonary edema; lymphadenopathy, 
metastatic disease, cardiac or pulmonary 
disorders. • Abdominal radiographs—effusion; 
altered hepatic size; mass lesions; pancreatic 
disease. • Abdominal ultrasonography—small 
liver, lymphangiectasia in intestinal wall/
mucosa, mass lesions, fluid pockets, altered 
portal blood flow, mesenteric lymphadenopathy, 
biliary tree abnormalities, renal abnormalities.
• Hepatic biopsy—after evaluating 
coagulation (mucosal bleeding time, platelet 
count) status. • Renal biopsy—differentiates

Canine and Feline, Seventh Edition  723
Hamyloidosis from glomerulonephritis; submit 
samples for special renal panel staining and 
electron microscopy. • Intestinal biopsy—
endoscopic or surgical.
Depend on underlying causal disease.
  TREATMENT
• Diverse, depends on cause. • Pleural/
peritoneal effusion restricting ventilation—
perform centesis.
Provide physical therapy and walk patient to 
improve mobilization of peripheral edema.
DIET
• Achieve positive energy and nitrogen 
balance. • HE—control protein intake (see 
Hepatic Encephalopathy). • PLE with IBD 
component—novel/hydrolyzed protein (see 
Inflammatory Bowel Disease). • PLE due 
to lymphangiectasia—feed ultra-low-fat 
diet. • PLN – feed high-quality/reduced-
Severe hypoalbuminemia delays healing, 
anesthetic drug metabolism, body cavity 
effusions may complicate drug dosing and 
dispersal, surgical approach, patient 
• Depend on underlying disease. 
• Glucocorticoids—for some types of chronic 
hepatitis and some PLEs; prednisolone is 
preferred if it is effective; dexamethasone lacks 
mineralocorticoid effects that lessens sodium 
and water retention, but has greater potential 
for ulceration/erosion. • Diuretics—furosem -
ide (1–4 mg/kg IV/IM/PO q4–12h) in 
q12h) in patients with hepatic or cardiac 
disease, combine with low-salt diet, use 
judiciously to avoid intravascular volume 
contraction; for body cavity effusion 
mobilization, taper diuretic dose after initial 
positive response; diuretics may be used 
intermittently to mobilize recurring ascites. 
• Antithrombotic treatment (low AT, PC, 
evidence of thrombi)—clopidogrel (0.5–
1.0 mg/kg PO q24h), especially in PLN. • Enalapril (0.5 mg/kg PO q12–24h)—for 
dogs with PLN; alternatives are benazepril or 
the angiotensin receptor blocker telmisartan 
(1 mg/kg PO q24h).
Synthetic colloids—avoid with anuria, renal 
failure, congestive heart failure, severe 
coagulopathy, or von Willebrand disease.
• Fluid therapy—avoid overdosing crystalloid 
fluids, especially when administered with 
synthetic colloids as these are rapidly 
distributed into interstitial spaces (70% 
volume within 1 hour), aggravating antecedent 
pulmonary or limb edema, and body cavity 
effusions; restrict maintenance fluid volume of 
crystalloids to one-third normal (depending on 
contemporary losses) when used with colloids. 
• T ransfusion of canine plasma or human 
albumin—may be complicated by transfusion 
or allergic reactions; plasma and albumin 
transfusions of dubious value if severe ongoing 
protein loss due to PLN, PLE, vasculitis. 
• Diuretic therapy—high doses may cause 
severe intravascular volume contraction leading 
to azotemia, hypotension, and electrolyte and 
acid-base derangements. • Unanticipated drug 
side effects—due to reduced albumin drug 
binding. • Use of 1 desamino-8-darginine 
vasopressin (DDAVP) for bleeding—may 
aggravate fluid retention and associated 
complications. • Glucocorticoids—
mineralocorticoid effects of some drugs may 
worsen fluid accumulation; prefer synthetic 
glucocorticoids without mineralocorticoid 
effects.
Inadvertent overdosing of drugs with 
high-protein binding.
  FOLLOW-UP
• Bodyweight—especially during fluid therapy; 
monitors fluid retention. • Vital signs, thoracic 
auscultation for crackles—monitor for 
pulmonary edema. • Sequential serum albumin 
concentrations. • Blood pressure—monitors 
vascular expansion. • Abdominal girth—
monitors ascites. • Central venous pressure—
unreliable; potentially dangerous in patients 
with bleeding or thrombotic tendencies.
Limit glucocorticoid exposure as much as 
possible; use alternative medications to 
control primary illness if possible.POSSIBLE COMPLICATIONS
• PLN/PLE—may be complicated by 
thromboembolism; minimize IV catheteri -
zation and trauma. • Hypovolemia—from 
dehydration, Addisonian crisis, blood loss, or 
diuretic overdose predisposes to acute renal 
failure, disseminated intravascular coagulation 
(DIC), or HE.
Depend on underlying cause.
Numerous diverse diseases or syndromes.
Condition complicates pregnancy.
SEE ALSO
• Lymphangiectasia.
• Portosystemic Vascular Anomaly, Congenital.
• DDAVP = 1 desamino-8-darginine 
• PC = protein C.
• PSS = portosystemic shunt.
• UP : UCr = urine protein : urine creatinine 
ratio.
Center SA. Fluid accumulation disorders. In: 
Willard MD, Tvedten H, eds, Small Animal 
Clinical Diagnosis by Laboratory Methods, 
5th ed. St. Louis, MO: Saunders, 2012, 
pp. 226–259.
Consulting Editor  Kate Holan(continued)  Hypoalbuminemia

724  Blackwell’s Five-Minute Veterinary Consult  
HHypocalcemia
  BASICS
Serum total and ionized calcium concentration 
below the reference range.
• Of total circulating serum calcium, 
40–50% is protein-bound, 40–50% is 
ionized, and 10% is complexed with other 
substances. Protein-bound and complexed 
calcium are unavailable for use by tissues. 
Only ionized calcium is available to tissues 
and is responsible for clinical problems (hypo 
and hypercalcemia).
• Mechanisms of hypocalcemia include:
◦ Low concentrations of binding proteins—  
◦ Reduced intestinal absorption—deficient 
vitamin D (renal disease, severe intestinal 
disease, rickets, chronic glucocorticoid 
◦ Reduced renal and bone resorption—  
hypoparathyroidism.
◦ Inadequate dietary intake.
◦ Excessive loss—lactation (eclampsia).
◦ Sequestration—saponification (acute 
pancreatitis).
◦ Binding/complexing with administered, 
ingested, or endogenous chemicals—
phosphate-containing enemas, citrate 
toxicosis (multiple citrate-containing 
anticoagulant transfusions), ethylene glycol 
toxicosis, oxalate toxicosis, low calcium/high 
phosphorus diet (nutritional secondary 
hyperparathyroidism), acute tumor lysis 
syndrome (hyperphosphatemia from cancer 
therapy-induced rapid destruction of tumor 
cells).
◦ Impaired synthesis or refractoriness to 
parathyroid hormone (PTH)—hypo  - 
magnesemia.
◦ Target organ calcitriol (vitamin D) 
resistance (vitamin D–dependent rickets 
type 2).
◦ Multifactorial—ionized hypocalcemia in 
critically ill patients.
• Cardiovascular—ECG changes and 
• Gastrointestinal—anorexia and vomiting 
(especially cats).
• Nervous/neuromuscular—seizures, tetany, 
ataxia, and weakness.
• Ophthalmic—posterior lenticular 
• Respiratory—panting.
Species
Small-breed bitches predisposed to eclampsia.Mean Age and Range
Variable
Variable
SIGNS
Signs of underlying disease may occur 
without clinical signs of hypocalcemia, 
because the latter do not occur until total 
serum calcium falls below 6.7 mg/dL. Severity 
of signs at a given calcium concentration are 
also dependent on rate of decrease; dogs with 
chronic hypocalcemia are less likely to show 
signs than dogs with acute hypocalcemia.
• Facial rubbing.
• Muscle trembling, twitching, or 
fasciculations.
• Ataxia or stiff gait.
• Panting.
• Ataxia, stiff gait, weakness, muscle 
fasciculation, trembling, twitching.
• Posterior lenticular cataracts in patients 
with primary hypoparathyroidism.
CAUSES
Nonpathologic Hypocalcemia
• Laboratory error—confirm true hypocalcemia, 
especially if clinical signs are not present.
• Hypoalbuminemia—most common cause 
(>50% of patients); reduction of protein-
bound calcium but not ionized calcium; not 
associated with clinical signs.
• Alkalosis—causes a reduction in ionized 
calcium while total can remain normal; not 
associated with clinical signs except in cases of 
borderline low serum ionized calcium 
Pathologic Hypocalcemia
• Primary hypoparathyroidism.
• Hypoparathyroidism secondary to bilateral 
thyroidectomy (or other corrective hyperthyroid 
therapies) causing parathyroid damage.
• Posthyperparathyroid correction due to 
prolonged negative feedback–induced 
hypofunction of normal parathyroid glands.
• Renal disease—acute or chronic.
• Ethylene glycol toxicosis.
• Oxalate toxicosis (lily, philodendron, etc.).
• Acute pancreatitis.
• Puerperal tetany—eclampsia.
• Phosphate-containing enemas.
• Intestinal malabsorption.
• Citrate toxicosis—multiple blood 
transfusions or improper citrate–blood ratio.• Rickets (rare)–hypovitaminosis D, 
decreased plasma calcitriol, target organ 
calcitriol receptor resistance (vitamin D–
dependent rickets type 2).
• Acute tumor lysis syndrome.
• Ionized hypocalcemia in critically ill patients. 
Multifactorial: parathyroid dysfunction; 
cytokine suppression of parathyroid function; 
vitamin D deficiency; hypomagnesemia; 
calcium chelation; accumulation of calcium in 
soft tissues, body fluids, and cells.
• Puerperal tetany—small-breed bitches 
during first 21 days of nursing, but can affect 
large breeds. Preparturient eclampsia reported 
in cats, rarely in dogs.
• Postcorrective procedures for 
hyperthyroidism and hyperparathyroidism.
  DIAGNOSIS
• Clinical signs of hypocalcemia—primary or 
secondary hypoparathyroidism, eclampsia, 
intoxication leading to rapid calcium 
binding/complexing (e.g., phosphate-
containing enemas, ethylene glycol); other 
causes rarely lower serum calcium enough to 
cause clinical signs.
• Neurologic signs—ethylene glycol toxicosis, 
primary neurologic disease.
• Vomiting—acute pancreatitis, intestinal 
malabsorption, renal failure, ethylene glycol 
• Bone pain or fractures—nutritional 
secondary hyperparathyroidism, neoplasia.
• Sodium bicarbonate causes alkalosis and 
lowers ionized calcium concentration.
• Samples collected in or contaminated by 
EDTA or citrate will be hypocalcemic.
Results
Hypoalbuminemia can lower total calcium 
concentration and is generally not associated 
with decreased ionized calcium. Patients with 
concurrent hypoalbuminemia and ionized 
hypocalcemia likely have a concurrent 
condition causing ionized hypocalcemia.
• Hypoalbuminemia with conditions causing 
protein loss, translocation, or decreased 
• High total CO2 with metabolic alkalosis.
• Azotemia—with acute and chronic kidney 
injury.
• Hyperphosphatemia with acute and chronic 
kidney injury, primary or secondary hypopara -
thyroidism, acute tumor lysis syndrome, or in

Canine and Feline, Seventh Edition  725
Hpatients receiving phosphate-containing 
enemas.
• High amylase and lipase in many, but not 
all, patients with acute pancreatitis or renal 
disease.
• Mild to moderate anemia possible with chronic 
renal failure, nutritional secondary hyperpara -
thyroidism, or intestinal malabsorption.
• Leukocytosis possible with acute pancreatitis.
• Isosthenuria with chronic kidney injury, 
moderate to advanced acute kidney injury.
• Glucosuria in some patients with acute 
kidney injury, diabetes with acute 
pancreatitis, ethylene glycol toxicosis, or 
oxalate toxicosis.
• Ionized calcium—helps determine if 
clinical signs are due to hypocalcemia.
• Ethylene glycol test—in patients suspected 
of ingesting ethylene glycol within previous 
12–16 hours (questionable reliability).
• Pancreatic lipase immunoreactivity—in 
patients suspected of having acute pancreatitis 
(questionable reliability if only test used).
• Intact PTH assay—if primary hypopara -
thyroidism is suspected.
• Serum magnesium concentration—
hypomagnesemia is rare cause of hypocalcemia.
• Plasma calcitriol (vitamin D, 1,25 
dihydroxycholecalciferol) concentration—to 
screen for rickets or vitamin D–dependent 
rickets type 2 (rare).
IMAGING
• Radiography usually normal.
• Small kidneys with chronic renal disease 
and large kidneys with acute kidney injury.
• Osteopenia and pathologic fractures with 
• Ultrasound—hyperechoic renal parenchyma 
with ethylene glycol or oxalate toxicosis, may 
identify pancreatitis or abdominal effusion.
ECG—prolongation of ST and QT 
segments; sinus bradycardia and wide T waves 
or T wave alternans in some patients.
  TREATMENT
• Inpatient treatment for clinical hypocalcemia.
• Emergency treatment indicated for primary 
or secondary hypoparathyroidism, eclampsia, 
hyperphosphatemia, citrate and ethylene 
• Long-term treatment for primary 
hypoparathyroidism and sometimes post-
thyroidectomy-associated PTH deficiency.
• Eclampsia—remove puppies from bitch 
and hand-nurse until weaned.DIET
Diet change recommended for nutritional 
secondary hyperparathyroidism (to a balanced 
diet) and renal failure (see Chronic Kidney 
Disease).
• Calcium gluconate 10% solution— 
5–15 mg/kg (0.5–1.5 mL/kg); give IV slowly 
to effect over 10 min; monitor heart rate and 
stop temporarily if bradycardia occurs; if 
ECG monitoring is possible, QT interval 
shortening is an indication to temporarily 
stop administration. Vomiting can indicate 
excessive calcium administration.
• Calcium chloride 10% solution—also 
effective but not recommended in small 
animals because it is extremely caustic if 
administered extravascularly. Three times 
more potent than calcium gluconate; mg/kg 
dosage is the same, but only one-third the 
volume is needed (0.15–0.5 mL/kg).
Short-Term Treatment Immediately  
after Correction of Tetany 
for Hypoparathyroidism
• Relapse of clinical signs can be prevented by 
use of IV CRI of calcium gluconate 10% 
solution (60–90 mg/kg/day [6.5–9.75 mL/
kg/day]) added to fluids that do not contain 
bicarbonate. Rarely necessary for 
postparturient eclampsia.
• Subcutaneous calcium gluconate 10% 
diluted 2–4 times with saline can be 
administered 3 or 4 times daily for initial 
control of tetany (reported to be safe in most 
patients, but there have been reports of 
marked and disabling inflammatory calcinosis 
cutis associated with subcutaneous use).
Long-Term Treatment
See Hypoparathyroidism.
Avoid bicarbonate, as alkalinization may 
further decrease serum ionized calcium levels.
Calcium salts may precipitate if added to 
solutions containing bicarbonate, lactate, 
acetate, or phosphates.
  FOLLOW-UP
• For patients requiring long-term therapy, 
serum calcium should be assessed 4–7 days following initial treatment, then (if 
normocalcemic) monthly for first 6 months, 
then every 2–4 months.
• Goal—maintain serum calcium 
concentration between 8 and 10 mg/dL.
• Vary dependent on underlying cause.
• Recurrence of hypocalcemia following 
calcium administration for primary hypopara -
thyroidism is common if calcitriol is not also 
administered; monitoring is advised.
• Hypocalcemia can lead to weakness and 
dystocia.
• Eclampsia in dogs is usually seen in first 
21 days of nursing a litter.
SEE ALSO
• Eclampsia.
• Ethylene Glycol Toxicosis.
• Lily Toxicosis.
Drobatz K, Casey KK. Eclampsia in dogs: 31 
cases (1995–1998). J Am Vet Med Assoc 
2000, 217:216–219.
Feldman EC. Hypocalcemia and primary 
hypoparathyroidism. In: Feldman EC, 
Nelson RW, Reusch CE, et al., eds., Canine 
and Feline Endocrinology and 
Reproduction, 4th ed. St. Louis, MO: 
Saunders, 2015, pp. 625–648.
Waters CB, Scott-Moncrieff JCR. 
Hypocalcemia in cats. Compend Contin 
Educ Pract Vet 1992, 14:497–507.
Author  Michael Schaer
available online(continued)  Hypocalcemia

726  Blackwell’s Five-Minute Veterinary Consult  
HHypochloremia
  BASICS
Serum chloride concentration below the 
lower limit of reference interval—dogs: 
<105 mEq/L; cats: <117 mEq/L (reference 
intervals may vary from laboratory to 
laboratory).
• Chloride is the most abundant anion in the 
• Chloride concentration is controlled by 
electrochemical gradients resulting from the 
active transport of sodium.
• In general, chloride concentration varies 
directly with sodium concentration and 
inversely with bicarbonate concentration.
Depends on underlying disorder.
GENETICS
N/A
N/A
Species
N/A
N/A
SIGNS
CAUSES
• Gastric vomiting.
• Metabolic alkalosis.
• Chronic respiratory acidosis.
• Excessive nasogastric suctioning.
• Excess total body water.
• Salt-losing nephropathy.
• Diuretic therapy (especially loop and 
thiazide diuretics).
• T reatment with bicarbonate.
• T reatment with laxatives.
N/A
  DIAGNOSIS
If the degree of hypochloremia exceeds that of 
hyponatremia, it suggests selective chloride 
loss, as seen in patients with gastric vomiting 
or metabolic alkalosis.LABORATORY FINDINGS
Potassium bromide therapy can cause 
pseudohyperchloremia, as many chemistry 
analyzers cannot differentiate bromide from 
chloride.
Results
Lipemia and hyperproteinemia can falsely 
lower chloride concentration if ion-specific 
electrodes are not used.
Yes
• Low chloride.
• Other abnormalities depend on underlying 
disorder, possibly hyponatremia, hyper-
kalemia, and high bicarbonate concentration.
• Measurement of urine fractional excretion 
of chloride may demonstrate high excretion.
• Blood gas measurement may reveal 
metabolic alkalosis.
N/A
N/A
  TREATMENT
• When choosing IV fluids, 0.9% NaCl has 
154 mEq/L of chloride, Normosol®-R and 
Plasma-Lyte-148® have 98 mEq/L of chloride, 
and lactated Ringer’s solution has 109 mEq/L 
of chloride; if fluid administration is 
indicated, 0.9% NaCl may increase chloride 
faster than the others; if both sodium and 
chloride concentrations are low due to excess 
free water, intravenous fluids may be 
contraindicated.
• If performing frequent nasogastric suctioning 
and removing large volumes of gastric residual 
volume, reinstallation of 2–3 mL/kg of 
aspirated volume may be considered. One 
study in dogs receiving routine nasogastric 
suctioning every 4 hours (average of 0.9 ± 
1.2 mL/kg/h of gastric volume removed) did 
not identify the development of 
hypochloremia over the course of 36 hours.
N/A
DIET
Depends on underlying disorder.SURGICAL CONSIDERATIONS
N/A
Other fluid therapy and medication as 
N/A
N/A
  FOLLOW-UP
Serum electrolyte concentrations as needed to 
ensure appropriate response.
Often accompanied by hyponatremia.
N/A
N/A
SEE ALSO
Hyponatremia
DiBartola SP . Fluid, Electrolyte and Acid-
Acid-Base and Electrolyte Disorders, 5th ed. 
New York: McGraw-Hill, 2000.

Canine and Feline, Seventh Edition  727
HHypoglycemia
  BASICS
Blood glucose concentration below the lower 
reference interval (generally <60 mg/dL).
Mechanisms responsible for hypoglycemia:
• Excess insulin or insulin-like factors (e.g., 
insulinoma, extrapancreatic paraneoplasia 
[insulin-like growth factor-2 (IGF-2)], xylitol 
toxicosis, iatrogenic insulin overdose).
• Reduced hepatic gluconeogenesis and 
glycogenolysis (e.g., hepatic disease, 
glycogen storage diseases, hypoadreno -
corticism, sepsis).
• Excessive metabolic use of glucose (e.g., in 
hunting dogs, pregnancy, neoplasia, 
polycythemia, and sepsis).
• Reduced intake or underproduction of 
glucose (e.g., in puppies and kittens, toy 
breeds, glycogen storage disease, and severe 
malnutrition or starvation).
• Nervous.
• Variable, depending on the underlying cause.
SIGNS
• Posterior paresis.
• Muscle fasciculations.
• Abnormal behavior.
• Lethargy and depression.
• Ataxia.
• Some animals appear normal aside from 
findings associated with underlying disease.
• Many animals have episodic signs.
• Polyneuropathy.
CAUSES
Endocrine
• Insulinoma.
• Extrapancreatic neoplasia associated with 
IGF-2 overproduction (e.g., hepatocellular 
carcinoma, hepatocellular adenoma, intestinal 
leiomyoma or leiomyosarcoma).
• Iatrogenic insulin overdose.
• Islet cell hyperplasia (nesidioblastosis).
Hepatic Disease
• Portosystemic shunt.
• Cirrhosis.
• Severe hepatitis (e.g., toxic and inflammatory).
• Glycogen storage diseases.Overuse
• Hunting dog (exertional) hypoglycemia.
• Sepsis—increased glucose utilization 
induced by cytokine production in 
macrophage-rich tissues.
Reduced Intake/Underproduction
• Young puppies and kittens.
• Toy-breed dogs.
• Severe malnutrition or starvation.
• In sepsis there is also cytokine-induced 
inhibition of gluconeogenesis in the setting of 
nutritional glycogen depletion.
Toxicosis
• Xylitol toxicosis.
• Antihyperglycemic agent toxicosis (e.g., 
sulfonylureas).
• Low energy intake predisposes to hypo -
glycemia in patients with conditions causing 
overuse and underproduction.
• Fasting, excitement, exercise, and eating 
may or may not increase the risk of 
hypoglycemic episodes in patients with 
insulinoma.
  DIAGNOSIS
• Patients with hyperinsulinism—signs of 
hypoglycemia or a normal physical 
• Patients with hypoadrenocorticism—  
waxing, waning, nonspecific signs (e.g., 
vomiting, diarrhea, melena, weakness); 
Addisonian patients that present in a crisis usu -
ally display hypovolemia and hyperkalemia 
rather than hypoglycemia (e.g., shock, 
bradycardia, dehydration).
• Patients with portosystemic shunts—
usually young to middle-aged; often thin or 
appear to have stunted growth; rarely, they 
have ascites or edema.
• Patients with cirrhosis and severe hepatitis 
usually have other signs of their disease (e.g., 
gastrointestinal abnormalities, icterus, and 
ascites or edema).
• Patients with sepsis—critical; usually in 
shock; pyrexia or hypothermia revealed by 
examination; may have gastrointestinal 
• Glycogen storage diseases—rare; usually 
younger animals.
• Extrapancreatic neoplasia and large 
neoplastic processes (hepatoma) that 
cause hypoglycemia may be detected by 
physical examination.LABORATORY FINDINGS
None
Procedures That May Alter Laboratory 
Results
Delayed separation of serum causes falsely 
low serum glucose values; if serum cannot be 
separated within 30 minutes of collection, it 
should be collected in a sodium fluoride 
(gray-stoppered) tube. Polycythemia may 
result in false hypoglycemia if measured on a 
point-of-care glucometer.
Yes
• Patients with hyperinsulinism may have 
normal results.
• Patients with hypoadrenocorticism may 
have hypocholesterolemia, hypoalbuminemia, 
lymphocytosis, eosinophilia, hyperkalemia, 
hyponatremia, azotemia, or hypercalcemia.
• Patients with congenital portosystemic shunts 
may have microcytosis, hypoalbuminemia, low 
blood urea nitrogen, slightly elevated liver 
enzyme activities, ammonium biurate 
crystalluria, and hyposthenuria. Serum 
bilirubin concentration sometimes increased.
• Patients with cirrhosis, severe hepatitis, and 
hepatic neoplasia may have anemia associated 
with chronic disease, high liver enzyme activities, 
hyperbilirubinemia, hypoalbuminemia, 
bilirubinuria, and hyposthenuria.
• Patients with xylitol toxicosis may have 
hypokalemia and later signs of hepatic failure.
• Simultaneous fasting glucose/insulin 
determination—indicated when insulinoma is 
suspected; plasma insulin concentration within 
the upper end or above reference range in the 
face of hypoglycemia (glucose <60 mg/dL) 
suggests insulinoma.
hormone stimulation test—to diagnose 
• Fasting and postprandial serum bile 
acids—diagnose portosystemic shunt or 
functional hepatic disease.
• Free abdominal fluid should be collected 
and analyzed.
• Fructosamine—chronic hypoglycemia will 
result in low fructosamine concentrations.
IMAGING
• Abdominal radiography and ultrasonography—  
useful in patients with extrapancreatic neoplasia 
and large neoplastic processes (may see 
organomegaly or masses), as well as portosystemic 
shunt (microhepatica), cirrhosis (microhepatica, 
hyperechogenicity), and severe hepatopathy. Not 
very sensitive nor specific for detecting 
insulinoma. Abdominal CT more accurately 
detects pancreatic endocrine tumors.

728  Blackwell’s Five-Minute Veterinary Consult  
H• Ultrasound-guided, laparoscopic, or 
surgical hepatic biopsy—useful to evaluate 
hepatic parenchymal disease.
• Technetium-99m quantitative hepatic 
scintigraphy—to detect portosystemic shunt.
• Mesenteric portography—to detect 
portosystemic shunt (requires surgery).
Ultrasound-guided or surgical tissue biopsy—
useful to evaluate hepatic parenchymal 
disorders and extrapancreatic neoplasia.
  TREATMENT
• Animals with clinical hypoglycemia should 
be treated as inpatients.
• If able to eat (i.e., responsive, no vomiting), 
feeding should be part or all of initial treatment.
• If unable to eat, start continuous IV fluid 
therapy with 2.5–5% dextrose solution.
• Surgery is indicated if a portosystemic shunt 
or neoplasia is the cause of hypoglycemia.
Emergency/Acute Treatment
• In hospital—administer 50% dextrose 
0.5 g/kg IV, diluted 1 : 3 as slow bolus. 
Glucagon as IV CRI at 5–10 ng/kg/min is 
transiently effective in cases of insulin-
secreting tumors.
• At home—client should not administer 
medication orally during a seizure; 
hypoglycemic seizures usually abate within 
1–2 min; if a seizure is prolonged, 
recommend transport to hospital; if a short 
seizure has ended or other signs of a 
hypoglycemic crisis exist, recommend 
rubbing corn syrup or 50% dextrose on the 
buccal mucosa, followed by 2 mL/kg of the 
same solution orally once the patient can 
swallow; then seek immediate attention.
• Owners of diabetic animals can be taught 
to inject prescribed glucagon 0.03 mg/kg IM.
• Initiate frequent feeding of a diet low in 
simple sugars or, if patient is unable to eat, 
continuous fluid therapy with 2.5 or 5% 
dextrose solution.
• See Insulinoma for treatment 
considerations.
• Hunting dog hypoglycemia—feed 
moderate meal of fat, protein, and complex 
carbohydrates a few hours before hunting; can feed snacks (e.g., dog biscuits) every 3–5 
hours during the hunt.
• Toy-breed hypoglycemia—increase 
frequency of feeding.
• Puppy and kitten hypoglycemia—increase 
• Other causes of hypoglycemia require 
treating the underlying disease and do not 
usually need long-term treatment (exception: 
glycogen storage disease type 1).
• Insulin.
• Barbiturates and diazepam do not treat 
cause in patients with hypoglycemic seizures; 
may potentially worsen hepatoencephalo -
pathy in patients with hepatic disease.
• 50% dextrose causes tissue necrosis and 
sloughing if given extravascularly; may cause 
phlebitis at concentrations above 5%.
• Administration of a dextrose bolus without 
subsequent frequent feedings or IV fluids 
with dextrose can predispose to hypoglycemic 
episodes.
N/A
  FOLLOW-UP
• Based on underlying disease.
• At home—for return or progression of 
clinical signs of hypoglycemia; assess serum 
glucose if signs recur.
• Single, intermittent serum glucose 
determinations may not reflect true glycemic 
status of patient because of counter-regulatory 
hormones.
• If due to insulin overdose in the diabetic (or 
postinsulinoma resection diabetes), reassess 
response to insulin with a blood glucose curve 
and adjust the insulin dose accordingly. 
Check for metastatic insulinoma.
Recurrent, progressive episodes of 
Prolonged hypoglycemia can cause transient 
(hours to days) to permanent dementia and 
blindness.AGE-RELATED FACTORS
Neonatal animals have poor glycogen storage 
capacity and reduced capacity for 
gluconeogenesis; thus, short periods of fasting 
(6–12 hours) can cause hypoglycemia. 
Important to remember when fasting prior to 
and following anesthesia.
Hypoglycemia can lead to weakness and 
dystocia.
SEE ALSO
• Leiomyoma, Stomach, Small and Large 
Intestine.
• Leiomyosarcoma, Stomach, Small and 
Large Intestine.
• Xylitol Toxicosis.
• IGF = insulin-like growth factor.
Caywood DC, Klausner JS, O’Leary, et al. 
Pancreatic insulin-secreting neoplasms: 
clinical diagnostic, and prognostic features 
in 73 dogs. J Am Anim Hosp Assoc 1988, 
24:577–584.
Cryer PE, Davis SN. Hypoglycemia. In: 
Longo DL, Fuaci AS, Kasper DL, et al. 
Harrison’s Principles of Internal Medicine, 
20th ed. New York: McGraw-Hill, 2018, 
pp. 2883–2889.
Lane SL, Koenig A, Brainard BM. 
Formulation and validation of a predictive 
model to correct blood glucose 
concentrations obtained with a veterinary 
point-of-care glucometer in hemodiluted and 
hemoconcentrated canine blood samples. J 
Am Vet Med Assoc. 2015, 246(3):307–312.
Nelson RW. Beta-cell neoplasia: insulinoma. 
In: Feldman E, Nelson R, Reusch C, 
Scott-Moncrieff JC, eds., Canine and Feline 
Endocrinology and Reproduction, 4th ed. 
St. Louis, MO: Saunders, 2015, pp. 348–375.
available onlineHypoglycemia  (continued)

Canine and Feline, Seventh Edition  729
HHypokalemia
  BASICS
Serum potassium concentration <3.5 mEq/L 
(normal range: 3.5–5.5 mEq/L).
• Potassium is primarily an intracellular 
electrolyte (98% of total body potassium is 
intracellular); serum levels, however, may not 
accurately reflect total body stores.
• It is predominantly responsible for the 
maintenance of intracellular fluid volume and 
required for normal function of many enzymes.
• Resting cellular membrane potential is 
determined by the ratio of intracellular to 
extracellular potassium concentration and 
maintained by the Na+/K+–adenosine triphos -
phate (ATPase) pump. Conduction disturbances 
in susceptible tissues (cardiac, nerve, muscle) are 
caused by rapid shifts in this ratio causing 
myoneural membrane hyperpolarization.
• Hypokalemia can be caused by decreased 
intake, loss (via the gastrointestinal tract or 
kidneys), or translocation of potassium from 
the extracellular to the intracellular fluid space.
• Neuromuscular—muscle weakness, 
including skeletal and muscles of respiration.
• Cardiac—electrocardiac changes and 
• Renal—hyposthenuria, nephropathy, and 
• Metabolic—acid-base balance (metabolic 
alkalosis); glucose homeostasis.
• Dogs and cats with predispositions to 
increased potassium loss, translocation of 
potassium, or decreased intake of potassium.
• Young Burmese cats with recurrent 
hypokalemic periodic paralysis episodes.
SIGNS
• Generalized muscle weakness or paralysis.
• Muscle cramps.
• Lethargy and confusion.
• Carbohydrate intolerance and weight loss.
• Polyuria (PU).
• Polydipsia (PD).
• Decreased bowel motility (humans; maybe 
dogs and cats).
• Ventroflexion of the neck.
• Respiratory muscle failure.
CAUSES
Decreased Intake
• Anorexia or starvation.
• Potassium deficient diet.
• Administration of potassium-deficient or 
potassium-free intravenous fluids.• Bentonite clay ingestion (e.g., clumping 
cat litter).
Gastrointestinal Loss
• Both upper and lower gastrointestinal 
obstruction, especially pyloric outflow 
Urinary Loss
• Chronic kidney disease (CKD).
• Hypokalemic nephropathy.
• Postobstructive diuresis.
• Dialysis (hemodialysis or peritoneal).
• Intravenous fluid diuresis.
• Hyperaldosteronism.
• Drugs (loop diuretics, amphotericin B, 
penicillins, fludrocortisone, desoxycorti -
costerone pivalate).
Translocation (Extracellular 
to Intracellular Fluid)
• Glucose administration.
• Insulin administration or release.
• Sodium bicarbonate administration.
• Catecholamines.
• Alkalemia.
• Beta2-adrenergic agonist overdose (e.g., 
albuterol, terbutaline).
• Hypokalemic periodic paralysis (Burmese 
cats).
• Rattlesnake envenomation (presumably 
from catecholamine release).
• Acidifying diets with negligible potassium.
• Diuresis or dialysis with potassium-
deficient fluids.
• Chronic illness (sustained anorexia and 
muscle wasting).
  DIAGNOSIS
• PU/PD, hyperglycemia, and glucosuria—
rule out diabetes mellitus.
• PU/PD, azotemia, and isosthenuria—  
rule out CKD and nephropathy, especially 
in cats.
• Vomiting, metabolic alkalosis, and 
hypochloremia—rule out upper gastro -
intestinal obstruction.
• Metabolic acidosis with urine pH >6.5—
rule out renal tubular acidosis.
• Urethral obstruction—rule out 
postobstructive diuresis.
• Hypertension with or without azotemia—
rule out hyperaldosteronism
• Young Burmese cat with episodic muscle 
weakness—rule out hypokalemic periodic 
paralysis.LABORATORY FINDINGS
Chemicals That May Alter Laboratory 
Results
Falsely elevated potassium measurement can 
be caused by excessive K3EDTA relative to the 
blood sample, as found in “purple-top” blood 
tube for hematology; not a problem with 
additive-free “red-top” tubes for serum).
Yes
• Hyperglycemia, glucosuria, ± ketonuria, 
± ketoacidosis in patients with diabetes mellitus.
• Normocytic, normochromic, nonregenerative 
anemia in patients with CKD.
• Elevated blood urea nitrogen (BUN) and 
creatinine concentrations, with isosthenuria in 
patients with CKD or hypokalemic nephropathy.
• Low total CO2 or HCO3–—in patients with 
renal tubular acidosis (RTA) or renal failure.
• Normal anion gap metabolic acidosis in RTA.
• Urine pH >6.5 in patients with distal 
• High total CO2 or HCO3–—in patients 
with metabolic alkalosis.
• High PCO2 with hypoventilation.
• Increased aldosterone and decreased renin 
in patients with primary hyperaldosteronism.
• Elevated urinary fractional excretion of 
potassium in patients with CKD, hypokalemic 
nephropathy, and primary hyperaldosteronism.
stimulation tests are used to diagnose adrenal 
gland disorders.
IMAGING
• Radiography, ultrasonography are helpful to 
diagnose gastrointestinal tract obstructions 
(mass or foreign bodies), pancreatitis, CKD 
workup, adrenal gland diseases (adrenocortical 
hyperplasia, adrenocortical neoplasia).
• Upper gastrointestinal barium study to 
additionally diagnose gastrointestinal 
obstructions (anatomic or functional).
• CT to further diagnose adrenal gland, 
renal, and gastroenteric disorders.
Upper gastrointestinal endoscopy to diagnose 
upper gastrointestinal disorders.
  TREATMENT
• Mild hypokalemia (3.0–3.5 mEq/L) can be 
treated by oral supplementation.
• Moderate hypokalemia (2.5–3.0 mEq/L) is 
best treated by inpatient administration of 
oral ± intravenous supplementation and 
carefully monitored.
• Patients with severe hypokalemia ( <2.5 
mEq/L) should be hospitalized for intensive 
intravenous potassium supplementation.

730  Blackwell’s Five-Minute Veterinary Consult  
H
Patients, especially cats, should be carefully 
monitored for cardiac arrhythmias, 
rhabdomyolysis and impaired ventilation.
• Oral supplementation with potassium 
gluconate (e.g., T umil-K®) is effective in 
mildly affected patients. The initial dosage 
is 2 mEq/4.5 kg bodyweight in food twice 
daily.
• Parenteral supplementation is required in 
anorectic or vomiting patients or in patients 
with moderate to severe hypokalemia ( <3.0 
mEq/L). Potassium chloride is added to 
intravenous fluids and delivered according to 
Table 1, best administered via infusion pump 
or with a pediatric fluid administration set 
(60 drops/mL). Monitor and taper 
accordingly.
• Provide magnesium sulfate, if hypomag -
nesemic; 1.0 mEq/kg/24h by CRI, or a 0.25 
mEq/kg slow IV bolus.
• Glucose supplementation.
• Insulin administration.
• Untreated hypoadrenocorticism.
• Oliguric or anuric renal failure or severe 
renal impairment.
• Rapid rehydration to correct severe 
dehydration (i.e., potassium-supplemented 
fluids should not be bolused IV).
Administer with caution, avoid over -
supplementation, do not bolus, monitor 
frequently.POSSIBLE INTERACTIONS
Concurrent potassium supplementation with 
angiotensin-converting enzyme (ACE) inhibitors 
(e.g., enalapril), potassium-sparing diuretics (e.g., 
spironolactone), prostaglandin inhibitors (e.g., 
nonsteroidal anti-inflammatory drugs), beta 
blockers (e.g., atenolol), or cardiac glycosides 
(e.g., digoxin) can cause adverse effects.
Potassium phosphate can be used in patients with 
concurrent hypophosphatemia where one-half of 
the potassium dose (in mEq) is administered in 
the form of potassium phosphate solution.
  FOLLOW-UP
Check serum potassium every 6–24 hours 
based on severity of hypokalemia.
Electrolyte disturbances and severe bradyar-
rhythmias. It is essential to close the IV fluid 
outflow valve and thoroughly mix the fluid 
contents when adding potassium chloride 
solution to the parenteral fluid bag.
None
N/A
SEE ALSO
• Alkalosis, Metabolic.
• ATPase = adenosine triphosphate.
• RTA = renal tubular acidosis.
Boag AK, Coe RJ, Martinez TA, et al. 
DiBartola SP , Autran de Morais H. Disorders 
of potassium: hypokalemia and hyperkalemia. 
In: DiBartola SP , ed., Fluid Therapy in Small 
Animal Practice, 4th ed. Philadelphia, PA: 
Saunders, 2012, pp. 92–120.
Greenlee M, Wingo CS, McDonough AA, 
et al. Narrative review: evolving concepts in 
potassium homeostasis and hypokalemia. 
Ann Intern Med 2009, 150: 619–625.
Nager AL. Fluid and electrolyte therapy in infants 
and children. In: Tintinalli JE, Stapczynski JS, 
Ma OJ, eds., Emergency Medicine: A 
Comprehensive Study Guide, 7th ed. New 
York: McGraw-Hill, 2011, pp. 971–976.
Consulting Editor  Patty A. LathanTable 1
Patient’s K+ Concentration KCl/L (mEq) Dosage (mEq K+/kg/h, IV)
3.5–4.5 20 0.05–0.1
3.0–3.5 30 0.1–0.2
2.5–3.0 40 0.2–0.3
2.0–2.5 60 0.3–0.4
<2.0 80 0.5–1.5
Note: do not exceed an intravenous supplementation rate of 0.5 mEq/kg/h unless continually monitoring 
and on the verge of ventilator muscle failure . With severe life-threatening hypokalemia (serum 
potassium <2.0 mEq/L), potassium chloride can be administered at a rate of 1.0–1.5 mEq/kg/h 
with ECG monitoring.Hypokalemia  (continued)

Canine and Feline, Seventh Edition  731
HHypomagnesemia
  BASICS
• Dogs—serum magnesium <1.89 mg/dL, 
ionized magnesium <0.43 mmol/L.
• Cats—serum magnesium <1.75 mg/dL, 
ionized magnesium <0.48 mmol/L.
• Magnesium is the second most abundant 
intracellular cation, found primarily in bone 
(60%) and soft tissues (38%).
• Hypomagnesemia has many causes; 
incidence rates >50% have been reported in 
critically ill humans.
(together 70–75%).
• Serum magnesium concentration does not 
always reflect whole-body magnesium status.
the ileum as well as the jejunum and colon.
• Kidneys maintain magnesium balance, with 
10–15% reabsorbed in the proximal tubule, 
60–70% in the thick ascending limb of the 
loop of Henle, and 10–15% reabsorbed in the 
distal convoluted tubule. Reabsorption within 
the distal convoluted tubule is under hormonal 
and neurohormonal control and determines 
the final urine concentration of magnesium.
sodium–potassium adenosine triphosphate 
(ATPase) pump that maintains a membrane 
electrical gradient. Magnesium is also important 
in the production and elimination of acetyl -
choline; hypomagnesemia can increase acetyl  - 
choline at motor endplates and cause tetany.
• Interference with membrane potentials can 
result in neuromuscular and cardiac 
• Magnesium regulates calcium movement 
into smooth muscle cells and is important for 
cardiac contractile strength, conduction, and 
peripheral vascular tone.
• Hypomagnesemia alters function of skeletal 
muscle, resulting in tetany and myopathies.
• Magnesium depletion affects membrane 
pumps on cardiac cells, resulting in depolari -
zation and tachyarrhythmias; cardiac arrhyth -
mias associated with hypomagnesemia include 
ventricular arrhythmias, torsades de pointes, 
QT prolongation, ST segment shortening, and 
widening of T waves; hypomagnesemia 
increases the risk of digoxin toxicity because 
both inhibit the membrane pump.
• Hypomagnesemia causes resistance to the 
effects of parathyroid hormone (PTH) and 
can increase the uptake of calcium into bone.
• Gastrointestinal.• Neuromuscular.
• Renal.
Reported in 28–54% of critically ill dogs and 
cats, may have increased incidence in 
bulldogs.
SIGNS
• Muscle fibrillation.
• Ataxia and depression.
• Hyperreflexia.
• Tetany.
• Behavior changes.
CAUSES
• Gastrointestinal—severe malnutrition or 
significant intestinal malabsorptive disease, 
following excessive loss of body fluids (e.g., 
severe, prolonged diarrhea), secretory large- 
• Renal—nephrotoxic drugs (e.g., cisplatin, 
aminoglycosides, amphotericin B), osmotic 
diuresis (e.g., with diabetes mellitus), loop 
diuretics, chronic thiazide diuretic therapy, 
hypercalciuria, postobstructive diuresis, and 
renal tubular acidosis.
• Other drugs associated with hypomag -
nesemia include cyclosporine, ticarcillin, 
carbenicillin, and proton pump inhibitors.
• Endocrine diseases associated with hypo -
magnesemia include hyperaldosteronism, 
hyperthyroidism, and primary hypopara -
thyroidism. Hypomagnesemia is found in 32% 
of dogs and 85% of cats with hypoparathy -
roidism, and can be seen following surgical 
parathyroidectomy.
• Lactation, pancreatitis, insulin admini -
stration, and catecholamine excess can cause 
excessive magnesium loss.
• Magnesium can be redistributed by 
refeeding after starvation and insulin therapy 
in diabetic patients.
• Causes of hypomagnesemia in the 
critically ill include decreased intake, lack 
of magnesium in parenteral fluids (long-
term fluid therapy or hemodialysis), use of 
a total parenteral nutrition formulation 
with inadequate magnesium content, 
excessive gastrointestinal loss, redistribu -
tion, and sequestration.
• Hypomagnesemia is associated with diabetes 
mellitus in humans, with nearly 25% of 
human diabetic outpatients having low serum 
magnesium, and may occur during therapy for 
diabetic ketoacidosis in dogs and cats.
• Gastrointestinal malabsorption syndromes.
• Polyuric renal disease.
• Diuretic administration.
• Diabetes mellitus and diabetic ketoacidosis.
• Total parenteral nutrition.• Peritoneal dialysis.
• Lactation.
  DIAGNOSIS
• Signs of hypomagnesemia are vague and 
multisystemic; therefore, other causes of 
neuromuscular abnormalities, especially other 
electrolyte abnormalities, must be investigated.
• Consider cardiac abnormalities, 
intoxications, and renal diseases.
Note: 12 mg of magnesium = 1 mEq of 
• Serum is favored over plasma because 
EDTA, sodium fluoride-oxalate, and sodium 
citrate anticoagulants used for plasma samples 
can contain citrate or other ions that bind 
magnesium. Heparinized whole blood or 
plasma may be used to determine ionized 
magnesium concentration
• Intravenous calcium gluconate can falsely 
decrease serum magnesium values.
Results
• Hemolysis can falsely elevate serum 
• Hypercalcemia ( >16 mg/dL) and 
hyperproteinemia ( >10 g/dL) can falsely 
elevate serum magnesium.
• Hyperbilirubinemia and lipemia can falsely 
decrease serum magnesium.
Yes
• Low serum magnesium.
• If patient is azotemic, consider renal causes.
• T ubular casts in urinary sediment might 
indicate nephrotoxicity.
• Hypokalemia, hyponatremia, and 
hypocalcemia are common findings with 
hypomagnesemia and should alert the clinician 
to the possibility of hypomagnesemia.
• Diagnosis of magnesium depletion can be 
difficult since <1% of total body magnesium 
is located in serum; only 55% of the 
magnesium in plasma is in the active 
(ionized) form; 33% is bound to plasma 
proteins and 12% is chelated with divalent 
anions such as phosphate and sulfate; 
magnesium assays (spectrophotometry) 
measure all three fractions.
magnesium status include measurement of

732  Blackwell’s Five-Minute Veterinary Consult  
Hmononuclear blood cell magnesium levels or 
quantifying retention from a loading dose.
• Urinary magnesium determination might 
help differentiate conditions associated with 
high urinary magnesium loss from conditions 
of low intake or absorption.
• Human studies suggest that retention of 
>40–50% of an administered magnesium load 
indicates magnesium depletion, while retention of 
<20% indicates adequate magnesium stores.
and electrocardiography) might reveal effects 
of hypomagnesemia, but will not differentiate 
the cause.
• Hypomagnesemia can cause prolongation 
of the PR interval, widening of the QRS 
complex, depression of the ST segment, and 
peaking of the T wave, in addition to 
ventricular arrhythmias.
  TREATMENT
and severity.
• Management includes treatment of the 
underlying condition(s) and magnesium 
replacement.
• Mild hypomagnesemia might resolve with 
treatment of the underlying disorder; however, 
if hypomagnesemia is severe, intensive care 
and magnesium replacement are needed.
Hypomagnesemia is a common finding in 
critically ill, hospitalized veterinary patients. 
Nursing should focus on the underlying 
disorder(s).
ACTIVITY
Based on concurrent conditions.
DIET
A balanced diet that takes into account all 
concurrent problems is appropriate.
• Magnesium sulfate or magnesium chloride.
◦ Emergency loading—0.15–0.3 mEq/kg 
IV over 15–60 min.
◦ Rapid replacement—0.75–1 mEq/kg/day 
(0.03 mEq/kg/h) IV.◦ Slow replacement—0.3–0.5 mEq/kg/day 
(0.013–0.02 mEq/kg/h) IV.
• Magnesium sulfate can be diluted in 5% 
dextrose in water or 0.9% saline; the solution 
of magnesium salts should be <20% and 
should use a separate IV port to minimize 
drug interactions
• Hypomagnesemia potentiates 
nephrotoxicity of aminoglycosides.
• Avoid cisplatin chemotherapy.
• Discontinue digoxin if possible.
• Use diuretics with caution.
• Hypermagnesemia is possible with 
overzealous supplementation.
• Azotemic patients should receive a lower 
dose of magnesium and more frequent 
monitoring than patients with normal 
kidney function.
• Magnesium sulfate is incompatible with 
sodium bicarbonate, hydrocortisone, and 
dobutamine HCl.
• Calcium-containing compounds lower 
serum magnesium concentration.
• Additive CNS depression can occur when 
parenteral magnesium is used with CNS 
depressant sedatives, neuromuscular blocking 
agents, and anesthetics.
• Combined use of parenteral magnesium 
sulfate and nondepolarizing neuromuscular 
blocking agents is contraindicated.
• Use magnesium supplementation cautiously 
with digitalis compounds to avoid conduction 
• Calcium supplements might negate the 
effects of parenteral magnesium.
  FOLLOW-UP
• Measure serum magnesium and calcium 
concentrations daily.
• Continuous ECG and blood pressure 
monitoring, especially during magnesium 
infusion.
• Severe hypomagnesemia can be fatal.
• Magnesium is inversely associated with 
fibroblast growth factor 23 (FGF23), an 
important prognostic factor in CKD in cats.EXPECTED COURSE AND PROGNOSIS
Outcome is dependent on resolution of the 
underlying disease(s).
Effects on fetus are identical to effects on the 
dam.
SEE ALSO
magnesium deficit and excess. In: 
Practice, 4th ed. Philadelphia, PA: Elsevier, 
2011, pp. 212–229.
Della Maggiore AM, Differential diagnosis 
for clinicopathologic abnormalities: 
potassium and magnesium. In: Ettinger SJ, 
Feldman EC, Cote E, eds., Veterinary 
Internal Medicine, 8th ed. Philadelphia, PA: 
Elsevier, 2017, pp. 270–275.
Hendrick D, van den Broek N, Chang Y, 
et. al. Prognostic importance of plasma total 
magnesium in a cohort of cats with 
azotemic chronic kidney disease. J Vet 
Intern Med 2018, 32(4):1359–1371.
Khanna C, Lund EM, Raffe M, et al. 
Hypomagnesemia in 188 dogs: a hospital 
population-based prevalence study. J Vet 
Intern Med 1998, 12(4):304–309.
Consulting Editor  Patty A. LathanHypomagnesemia  (continued)

Canine and Feline, Seventh Edition  733
HHypomyelination
  BASICS
OVERVIEW
• Also known as “shaking puppies.” 
• Congenital deficit in myelin deposition 
caused by either delayed myelination or a 
permanent lack of myelin at birth. • Axons 
>1–2 mm in diameter have a myelin cover 
produced by oligodendrocytes in the central 
nervous system (CNS) and Schwann cells in 
the peripheral nervous system (PNS); myelin 
insulates axons and facilitates propagation of 
action potentials. • Affected axons with 
deficit in myelin deposition can alter impulse 
conduction or trigger spontaneous discharges 
and then generate tremors; the degree of 
tremor is usually correlated with the severity 
of the abnormal myelin deposition.
CNS
• Clinical signs appear at birth or when the 
puppy starts to ambulate. • Dog—springer 
spaniel, Samoyed, chow chow, Weimaraner, 
Bernese mountain dog, Dalmatian, Catahoula, 
rat terrier, border terriers, and lurcher. 
• Cat—Siamese and presumed in domestic 
shorthair and Birman cats. • Predominant sex 
(X-linked)—springer spaniel and Samoyed 
male puppies clinically affected, whereas 
females remain largely asymptomatic carriers; 
no sex differences reported in other breeds.
PNS
• Dog. • Golden retriever—reported in both 
sexes.
SIGNS
CNS
• Action-related repetitive myoclonus—rapid 
contractions and relaxation of diffuse skeletal 
muscles manifested as generalized body tremors 
that worsen with exercise and subside during 
rest or sleep; some affected dogs and cats appear 
to be “bouncing.” • The tremors diminish with 
time in the majority of affected dogs and usually 
resolve by 12 months of age or earlier; however, 
some dogs can retain a persistent fine tremor of 
the pelvic limbs. • Some dogs also present with 
head bobbing and nystagmus. • In rat terriers, 
associated with goiter and clinical signs of 
congenital hypothyroidism. • Springer spaniels 
and Samoyeds are usually affected for life.
PNS
• Clinical signs appear at 5–7 weeks of age. 
• Generalized weakness, pelvic limb ataxia and 
paresis, muscle wasting, and hyporeflexia that 
improve with age. • T remors are not present.
• Genetic—X-linked recessive condition for 
CNS disease in springer spaniels and autosomal 
recessive gene in rat terriers, Weimaraners, and 
border terriers. • Genetic basis speculative for 
other breeds. • Mutation identified in Weimaraners and rat terriers. • The carrier 
frequency in Weimaraners has been estimated to 
be 4.3%. • Viral or toxic—possible in some 
breeds. • PNS—undetermined; possibly genetic.
  DIAGNOSIS
CNS
• Cerebellar hypoplasia or abiotrophy—tremors 
in neonates; but cerebellar ataxia (hypermetric 
gait) and intention tremors more prominent. 
• Storage diseases—associated with tremors; 
neonates are normal. • Generalized tremor 
syndrome in dogs (historically identified as 
“white shakers” but other hair coat colors can be 
affected)—affected dogs are usually >8 months 
old. • Metabolic diseases (hypocalcemia, 
hypernatremia, hyponatremia, hypoglycemia). 
• Feline polioencephalomyelitis—young to 
middle-aged cats; other neurologic signs are 
present (paresis, seizures, hyperesthesia). 
• Toxic—organophosphates, permethrins, 
mycotoxins: history of exposure to a toxic 
product.
PNS
• Muscular dystrophy—serum creatine kinase 
highly elevated. • Congenital myasthenia gravis. 
• Other polyneuropathies or myopathies.
IMAGING
MRI—may detect white matter changes on 
CNS form.
CNS
• Presumed diagnosis based on signalment, 
clinical signs, and evolution. • Histopathology 
(necropsy). • DNA test for causative genetic 
mutation (currently available for Weimaraners 
and rat terriers).
PNS
• Electromyography—usually normal to mild 
diffuse spontaneous activity. • Motor nerve 
conduction velocity—small or no evoked 
potentials and slowed conduction. • Nerve 
biopsy—insufficient myelin surrounding 
peripheral axons.
  TREATMENT
None effective for either form.
Avoid breeding from affected animals in 
which a genetic cause is suspected.
PROGNOSIS
• CNS—Springer spaniels and Samoyeds 
affected for life; other breeds usually improve 
by 1 year of age. • PNS—dogs have normal 
lifespan.
• CNS = central nervous system.
• PNS = peripheral nervous system.
Genetic Tests
• https://www.vgl.ucdavis.edu/services/
Weimaraner.php • https://www.
centerforanimalgenetics.com/services/
dog-genetic-testing/hereditary-disease-testing-
for-dogs/congenital-hypothyroidism • http://
www.laboklin.co.uk/laboklin/
showGeneticTest.jsp?testID=8443
Video
http://www.neurovideos.vet.cornell.edu/
Video.aspx?vid=20-39
Duncan ID. Abnormalities of myelination of 
the central nervous system associated with 
congenital tremor. J Vet Intern Med 1987, 
1:10–23.
Lowrie M, Garosi L. Classification of 
involuntary movements in dogs: tremors 
and twitches. Vet J 2016, 214:109–116.
Martin-Vaquero P , da Costa RC, Simmons 
JK, et al. A novel spongiform 
leukoencephalomyelopathy in Border 
Terrier puppies. J Vet Intern Med 2012, 
26:402–406.
Millán Y, Mascort J, Blanco A, et al. 
Hypomyelination in three Weimaraner 
dogs. J Small Anim Pract 2010, 
51:594–598.
Pemberton TJ, Choi S, Mayer JA, et al. 
A mutation in the canine gene encoding 
folliculin-interacting protein 2 (FNIP2) 
associated with a unique disruption in 
spinal cord myelination. Glia 2014, 
62:39–51.
Stoffregen DA, Huxtable CR, Cummings JF , 
et al. Hypomyelination of the central 
nervous system of two Siamese kitten 
littermates. Vet Pathol 1993, 30:388–391.
Author  Elsa Beltran

734  Blackwell’s Five-Minute Veterinary Consult  
H  BASICS
Serum sodium concentration below the lower 
limit of the reference range.
Sodium is the most abundant cation in the 
extracellular fluid. Hyponatremia usually reflects 
hypo-osmolality and is typically associated with a 
decreased total body sodium content. Either water 
retention or solute loss can cause hyponatremia. 
Most solute loss occurs in iso-osmotic solutions 
(e.g., vomit and diarrhea) and, as a result, water 
retention in relation to solute is the underlying 
cause in almost all patients with hyponatremia. In 
general, hyponatremia occurs only when a defect 
in renal water excretion is present.
• Nervous—severe neurologic dysfunction is 
not usually seen until serum sodium concen -
tration falls below 110–115 mEq/L. Clinical 
signs may be more related to the rate of decline 
in serum sodium concentration than the actual 
nadir. Dogs with chronic hyponatremia often 
have mild, if any, clinical signs.
• Overly rapid correction of hyponatremia 
can also cause neurologic damage.
Species
SIGNS
• Confusion.
• Nausea/vomiting.
• Obtundation.
• Coma.
• Other signs depend on the underlying 
cause.
CAUSES
Normal Osmolar Hyponatremia
• Hyperlipidemia (pseudohyponatremia).
• Hyperproteinemia (pseudohyponatremia).
Hyperosmolar Hyponatremia
• Mannitol administration.
Hypo-osmolar Hyponatremia
Normovolemic
• Primary polydipsia.
• Hypothyroid myxedema coma.
• Hypotonic fluid infusion.
• Syndrome of inappropriate antidiuretic 
hormone secretion (SIADH).
Hypervolemic
• Hepatic cirrhosis.
• Severe renal failure.Hypovolemic
• Gastrointestinal losses.
• Third-space losses.
• Cutaneous losses (e.g., burns).
• Diuresis.
  DIAGNOSIS
• Severe gastrointestinal disease.
• Metabolic or respiratory acidosis.
Drugs That May Alter Lab Results
Mannitol can cause pseudohyponatremia by 
solvent drag.
Disorders That May Alter Lab Results
Hyperlipidemia and hyperproteinemia can cause 
pseudohyponatremia on analyzers that use 
indirect potentiometry or flame photometry. 
Hyperglycemia can cause pseudohyponatremia 
through solvent drag, and serum sodium 
concentration normalizes with correction of 
hyperglycemia (e.g., with IV fluid or insulin 
therapy in patients with diabetes mellitus).
Yes
• Low serum sodium concentration.
• Other abnormalities may point to the 
• Plasma osmolality is usually low; if plasma 
osmolality is normal or high, exclude hyperlipi -
demia, hyperglycemia, hyperproteinemia, and 
mannitol administration.
• Urine osmolality <100–150 mOsmol/kg 
indicates primary polydipsia or reset 
osmostat. Urine osmolality >150–
200 mOsmol/kg indicates impaired renal 
water excretion.
• Urine sodium concentration <15–20 mEq/L 
indicates low effective circulating volume, pure 
cortisol deficiency, or primary polydipsia with 
high urine output. Urine sodium concentration 
>20–25 mEq/L indicates SIADH, adrenal 
insufficiency, renal failure, reset osmostat, 
diuretic administration, or vomiting with 
marked bicarbonate loss.
  TREATMENT
Generally inpatient, depending on severity of 
hyponatremia, associated neurologic 
dysfunction, and underlying disorder.  MEDICATIONS
• T reatment consists of addressing the underlying 
cause and increasing the serum sodium 
concentration if necessary. Overly rapid 
normalization (>10-12 mEq/L in 24 hours) of 
chronic hyponatremia can have potentially severe 
neurologic sequelae (myelinolysis) and may be more 
detrimental than the hyponatremia itself. Therefore, 
an isotonic crystalloid is the fluid of choice in most 
cases. More aggressive correction of serum sodium 
with hypertonic or normal saline in patients with 
chronic hyponatremia is not recommended.
• Acute hyponatremia (occurring over 24–48 
hours) can be corrected more quickly, but is 
rare in small animals. Unless an acute cause of 
hyponatremia can be identified, or severe 
clinical signs of hyponatremia are present 
(seizures, cerebral edema), slower correction is 
• Hypervolemic (edematous) patients are 
typically managed with diuretics and salt 
restriction, or hemodialysis if necessary (e.g., 
acute renal failure).
• Hypovolemic patients are managed by 
replacing the volume deficit with isotonic 
crystalloids. Isotonic (0.9%) saline, Normosol®-R, 
and lactated Ringer’s solution (LRS) may be 
used. LRS has a sodium concentration of 
130 mEq/L and is helpful in slowly increasing 
sodium concentrations in dogs with severe 
hyponatremia (<120 mEq/L).
• Other therapeutic interventions are dictated 
by the underlying cause of the hyponatremia.
Overly rapid correction of hyponatremia can 
result in neurologic damage (demyelination); 
avoid increasing serum sodium concentration by 
more than 10–12 mEq/L/day (0.5 mEq/L/h).
  FOLLOW-UP
• Serial serum sodium determinations 
(generally q4–6h) to avoid overly rapid 
correction of the serum sodium concentration 
and to assure appropriate response to other 
• Monitor hydration status.
• Monitor other serum electrolyte concen -
trations as indicated by the patient’s clinical 
condition and underlying disorder.
Depends on the underlying disorder.
Depends on the underlying disorder.Hyponatremia

Canine and Feline, Seventh Edition  735
Other electrolyte and acid-base abnormalities 
are often associated with the clinical disorders 
that cause hyponatremia.
SEE ALSO
• Chronic Kidney Disease.• Cirrhosis and Fibrosis of the Liver.
• Hyperlipemia.
• Myxedema and Myxedema Coma.
• LRS = lactated Ringer’s solution.
• SIADH = syndrome of inappropriate ADH 
secretion. Suggested Reading
Melinda Fleming.(continued)  Hyponatremia

H736  Blackwell’s Five-Minute Veterinary Consult  
HHypoparathyroidism
  BASICS
Absolute or relative deficiency of parathyroid 
hormone (PTH) secretion leading to hypo- 
calcemia.
• Dogs—most commonly idiopathic 
immune-mediated parathyroiditis, rarely 
following bilateral thyroidectomy or following 
severe cervical trauma. • Cats—most 
commonly iatrogenic secondary to damaged or 
removed parathyroid glands during 
thyroidectomy; idiopathic atrophy and 
immune-mediated parathyroiditis uncommon.
bradycardia. • Gastrointestinal—anorexia 
and vomiting, possibly (altered gastro -
intestinal muscular activity). • Nervous/
neuromuscular—seizures, tetany, ataxia, 
weakness (diminished neuronal membrane 
stability). • Ophthalmic—posterior 
lenticular cataracts. • Respiratory—panting 
(neuromuscular weakness, anxiety).
• Dog—uncommon. • Cat—common 
(10–82%) following bilateral thyroidectomy; 
spontaneous occurrence rare.
Species
Toy poodle, miniature schnauzer, German 
shepherd dog, Labrador retriever, terrier 
breeds; mixed-breed cats.
• Dogs—mean 4.8 years; range: 6 weeks–13 
years. • Cats—secondary to thyroidectomy, 
mean 12–13 years; range: 4–22 years. • Cats—
spontaneous, mean 2.25 years; range: 6 
months–7 years.
Dogs—female (60%); cats—male (64%).
SIGNS
Dogs
• Seizures (49–86%). • Ataxia/stiff gait 
(43–62%). • Facial rubbing (62%). • Muscle 
trembling, twitching, and fasciculations 
(57%). • Growling (57%). • Panting (35%). 
• Weakness. • Vomiting. • Anorexia.
Cats
• Lethargy, anorexia, and depression (100%). 
• Seizures (50%). • Muscle trembling, 
twitching, and fasciculations (83%). 
• Panting (33%). • Bradycardia (17%).Physical Examination Findings
Dogs
• Tense, splinted abdomen (50–65%). • Ataxia/
stiff gait (43–62%). • Fever (30–70%). • Muscle 
trembling, twitching, and fasciculations (57%). 
• Panting (35%). • Posterior lenticular cataracts 
(15–32%). • Weakness. • Normal physical 
examination (20%).
Cats
• Muscle trembling, twitching, and fasciculations 
(83%). • Panting (33%). • Posterior lenticular 
cataracts (33%). • Bradycardia (17%). • Fever 
(17%). • Hypothermia (17%).
CAUSES
Dogs, cats—bilateral thyroidectomy.
  DIAGNOSIS
Seizures
• Cardiovascular—syncope. • Metabolic—
hepatoencephalopathy, hypoglycemia, other 
causes of hypocalcemia. • Neurologic—
epilepsy, neoplasia, toxin, inflammatory 
disease.
Weakness
• Cardiovascular—congenital defects, arrhyth -
mias, heart failure, pericardial effusion. 
• Metabolic—hypoadrenocorticism, hypo -
glycemia, anemia, hypokalemia (especially cats), 
hypothyroidism. • Neurologic/neuromuscular—
myasthenia gravis, polymyositis, polyradiculoneu -
ropathy, spinal cord disease. • Toxic—tick 
paralysis, botulism, chronic organophosphate 
exposure, snake envenomation (Eastern coral 
snake and other elapids, Mojave and certain other 
pit vipers), lead poisoning.
Muscle Trembling, Twitching, 
and Fasciculations
• Metabolic—puerperal tetany (i.e., 
eclampsia), other causes of hypocalcemia. 
• Toxic—tetanus, strychnine, permethrin, 
snake envenomation.
• Hemogram and urinalysis usually normal; 
perform to rule out other differential 
diagnoses. • Hypocalcemia (usually <6.5 mg/
dL) and normal or mild to moderate hyper -
phosphatemia. • Evaluate serum albumin 
carefully in all patients with hypocalcemia; 
hypoalbuminemia is most common asympto -
matic cause of hypocalcemia (assuming 
ionized fraction is adequate). • The only other 
intrinsic disease process besides hypoparathy -
roidism that reduces serum calcium and raises 
serum phosphorus is renal failure, which is 
easily distinguished from hypoparathyroidism 
by presence of azotemia; highly concentrated phosphate enema solutions can also cause 
hyperphosphatemia and hypocalcemia, as can 
excessive potassium phosphate parenteral fluid 
Serum PTH—undetectable or very low PTH 
concentration; patients with other processes 
causing hypocalcemia (e.g., renal failure) have 
normal to high serum PTH concentration.
IMAGING
Atrophic parathyroid glands will not be visible 
with ultrasonography (normally 2–3 mm).
• ECG changes from hypocalcemia include 
prolongation of ST and QT segments; sinus 
bradycardia and wide T waves; occasionally  
T wave alternans. • Cervical surgical 
exploration reveals absence or atrophy of 
• Dogs—normal or diminished tissue with mature 
lymphocytes, plasma cells, and fibrous connective 
tissue along with chief cell degeneration. • Cats—
parathyroid gland atrophy more common, 
although histopathologic findings similar to dogs 
also found.
  TREATMENT
• Hospitalize for medical management of 
hypocalcemia until clinical signs of hypo -
calcemia are controlled and serum total 
calcium concentration is >7 mg/dL.
• See Hypocalcemia for emergency inpatient 
management and appropriate fluid therapy
No specific care other than seizure watch.
DIET
Avoid calcium-poor diets; for dogs, puppy 
diets generally higher in calcium than adult 
dog food.
• Naturally occurring primary hypopara -
thyroidism requires lifelong therapy and 
monitoring. • Most cases of iatrogenic hypo -
parathyroidism (e.g., bilateral thyroidectomy) 
will recover over days to months and only require 
transient management and monitoring.
Emergency/Acute Therapy
See Hypocalcemia.
Short-Term Post-tetany Therapy

Canine and Feline, Seventh Edition  737
HH
Long-Term Therapy
• Vitamin D administration is needed 
indefinitely for primary hypoparathyroidism 
and total parathyroidectomy; dosage should 
be adjusted based on serum calcium concen -
tration. • Shorter-acting preparations of 
vitamin D are preferred so that overdosage 
(causing hypercalcemia) can be quickly 
corrected (see Table 1). • A more economical 
approach to treatment is to maximize oral 
administration of calcium and reduce oral 
administration of vitamin D (see Table 2); 
calcium is usually less expensive than vitamin 
D; dosage is influenced by each product’s 
available elemental calcium content.CONTRAINDICATIONS
Hypercalcemia
All calcium preparations given orally can cause 
nausea and constipation; calcium carbonate may 
be less irritating because of its high calcium 
availability and lower dosage requirement.
• Injectable and sometimes oral calcium 
solutions and tablets are incompatible with 
tetracycline drugs, cephalothin, methylpredni -
solone sodium succinate, dobutamine, 
 metoclopramide, and amphotericin B. 
• Thiazide diuretics used in conjunction with large doses of calcium may cause hypercalcemia. 
• Patients on digitalis are more likely to develop 
arrhythmias if calcium is administered 
intravenously. • Calcium administration may 
antagonize effects of calcium channel 
blocking agents.
  FOLLOW-UP
• Hypocalcemia and hypercalcemia are both 
concerns with long-term management. • Once 
serum calcium is stable and normal, assess Vitamin D preparations.
Preparation Dose Maximal Effect Size
1,25 Dihydroxycholecalciferol (active vitamin D3, 
calcitriol)0.03–0.06  μg/kg/day 1–4 days 0.25 and 0.5  μg capsules, 1.0  μg/mL 
oral solution, and 1 and 2  μg/mL 
injectable
Dihydrotachysterol Initial—0.02–0.03 mg/kg/day
Maintenance—0.01–0.02 mg/
kg/24–48h1–7 days Currently unavailable in United States; 
formerly available as 0.125 mg, 
0.2 mg, 0.4 mg tablets and 0.2 mg/
mL syrup
Ergocalciferol (vitamin D2) Initial—4000–6000 U/kg/day 
Maintenance—1000–2000 U/kg/
day–week5–21 days 25,000 and 50,000 U capsules and 
8000 U/mL syrup
Calcium preparations.
Preparation Dose of Elemental Calcium Available Calcium Size Available (Needs to Be Converted to Elemental Calcium)
Calcium carbonate Canine—1–4 g/day
Feline—0.5–1 g/day40% Tablets—500, 600, 650, 1250, 1500 mg
Chewable tablets—400, 420, 500, 750, 50, 1000, 1250 mg
Capsules—1250 mg
Oral suspension—250 mg/mL
Calcium gluconate Canine—1–4 g/day
Feline—0.5–1 g/day10% Tablets—500, 650, 975 mg
Chewable tablets—500 mg
Capsules—500, 700 mg
Powder for suspension—70 mg/mL
Calcium lactate Canine—1–4 g/day
Feline—0.5–1 g/day13% Tablets—650, 770 mg
Capsules—500 mg
Calcium acetate Canine—1–4 g/day
Feline—0.5–1 g/day25% Tablets, gelcaps, and capsules—667 mg
Calcium citrate Canine—1–4 g/day
Feline—0.5–1 g/day21% Tablets—950, 1150 mg
Effervescent tablets—2,380 mg
Capsules—850, 1070 mg
Powder for oral suspension—725 mg/mL
Calcium glubionate Canine—1–4 g/day
Feline—0.5–1 g/day30% Syrup—360 mg/mL(continued)  Hypoparathyroidism
Table 1
Table 2

738  Blackwell’s Five-Minute Veterinary Consult  
Hserum calcium concentration monthly for the 
first 6 months, then every 2–4 months; goal is 
to maintain serum total calcium between 8 and 
10 mg/dL. • Inform clients about clinical signs 
of hypo- and hypercalcemia.
• Hypocalcemia if undertreated. • Hypercalcemia, 
which can lead to nephrocalcinosis and kidney 
injury (see Hypercalcemia) and resistance to 
• With close monitoring of serum calcium and 
client dedication, the prognosis for long-term 
survival is excellent. • Adjustments in vitamin 
D and oral calcium administration can be 
expected during the course of management, 
especially during the initial 2–6 months. 
• Cats with hypoparathyroidism secondary to 
thyroidectomy usually require only transient 
treatment because they typically regain normal 
parathyroid function within 4–6 months, 
often within 2–3 weeks.  MISCELLANEOUS
Excess muscular activity can lead to 
hyperthermia, which may necessitate treatment.
Hypocalcemia can lead to weakness and 
dystocia.
SEE ALSO
Feldman EC, Nelson RW. Hypocalcemia and 
primary hypoparathyroidism. In: Feldman 
EC, Nelson RW, Reusch CE, et al., eds., 
Canine and Feline Endocrinology, 4th ed. St. Louis, MO: Saunders, 2015, 
pp. 625–646.
Henderson AK, Mahony O. 
Hypoparathyroidism: pathophysiology and 
diagnosis. Compend Contin Educ Pract Vet 
2005, 27(4):270–279.
Hypoparathyroidism: treatment. Compend 
Contin Educ Pract Vet 2005, 27(4): 
280–287.
Peterson ME, James KM, Wallace M, et al. 
Idiopathic hypoparathyroidism in five cats. 
J Vet Intern Med 1991, 5:47–51.
available onlineHypoparathyroidism  (continued)

Canine and Feline, Seventh Edition  739
HHypophosphatemia
  BASICS
Serum phosphorus concentration <2.5 mg/dL.
• Control of phosphorus is influenced by the 
actions and interactions of PTH and vitamin D 
with the gastrointestinal tract, bone, kidneys, 
and parathyroid glands.
• Decreased serum phosphorus 
concentration can be caused by translocation 
of phosphorus from the extracellular fluid 
into cells, decreased renal reabsorption, or 
decreased intestinal absorption of 
• Low serum phosphorus can lead to 
adenosine triphosphate (ATP) depletion, 
which affects cells with high ATP energy 
demands (skeletal muscle, cardiac muscle, 
nerve tissue, and red blood cells).
• Many important enzyme systems are 
dependent on adequate phosphorus levels, 
including glycolysis, ammoniagenesis, 
1-hydroxylation of 25(OH)-cholecalciferol, 
and 2,3-diphosphoglycerate, which are 
essential for energy production, acid 
excretion, calcium balance, and tissue 
oxygenation, respectively.
• Phosphorus is also required for mainten -
ance of cell membrane integrity, playing an 
essential role in the production of ATP , 
guanosine triphosphate, cyclic adenosine 
monophosphate (AMP), and phospho  - 
• Diabetic (ketototic and nonketotic) 
patients are at increased risk for hypophos -
phatemia due to depleted phosphorus 
stores, lost muscle mass, and urinary losses. 
Insulin administration yields ATP from 
glycolysis, causing translocation of 
• Hemic/lymphatic/immune—hemolysis, 
impaired oxygen delivery to tissues, impaired 
leukocyte and platelet function.
• Neurologic—impaired glucose uptake 
leads to encephalopathy, seizures, and coma.
• Musculoskeletal—rhabdomyolysis, weakness, 
pain, ventilatory failure, and gastrointestinal 
ileus.
• Cardiac—impaired contractility.
• Older dog and cat.
• Diabetic patient.
• Keeshonden have genetic predisposition to 
SIGNS
Usually consistent with the primary condition 
responsible for the hypophosphatemia; however, evidence of severe hypophosphatemia 
(e.g., hemolysis) is usually not observed unless 
serum concentrations decrease to 1.0 mg/dL 
or less.
• Hemolytic anemia (especially in cats) causes 
pallor, tachypnea, dyspnea, and/or hemoglob- 
inuria.
• Skeletal and respiratory muscle weakness.
• Mental dullness.
CAUSES
• Maldistribution (translocation)—
treatment of diabetic ketoacidosis, insulin 
administration or carbohydrate load, 
total parenteral nutrition or nutritional 
recovery, hyperventilation or respiratory 
• Reduced renal reabsorption (increased 
renal loss)—primary hyperparathyroidism, 
renal tubular disorders (e.g., Fanconi 
syndrome), proximal tubule diuretics (e.g., 
carbonic anhydrase inhibitors), eclampsia 
(puerperal tetany), hyperadrenocorticism 
(corticosteroids promote renal phosphate 
loss), sodium bicarbonate administration.
• Reduced intestinal absorption (decreased 
intake)—phosphorus-deficient diets, vitamin 
D deficiency, malabsorption disorders, 
• Laboratory error—hemolysis, icterus, 
osmotic diuretic administration.
• Phosphorus-deficient diets or parenteral 
nutrition (refeeding syndrome).
• Prolonged anorexia, malnutrition, or 
starvation.
  DIAGNOSIS
• Concurrent hyperglycemia, glucosuria, 
ketonuria, and high anion gap metabolic 
acidosis—rule out diabetic ketoacidosis.
• Concurrent glucosuria, normoglycemia, 
isosthenuria with or without azotemia—rule 
out renal tubular defects.
• Concurrent hypercalcemia and proteinuria, 
hematuria, with or without bacteria—rule 
out primary hyperparathyroidism with cystic 
calculi or nephroliths.
• Concurrent hypocalcemia—rule out 
puerperal tetany.
• Concurrent panhypoproteinemia—rule out 
intestinal malabsorption.
Liposomal amphotericin B (depending on 
assay).Disorders That May Alter Laboratory 
Results
Monoclonal gammopathy may falsely lower 
serum phosphorus concentrations by binding 
to inorganic phosphorus.
Valid If Run In Human Laboratory?
Yes
• Serum phosphorus <2.5 mg/dL.
• Hyperglycemia, glucosuria, ketonuria, and 
high anion gap metabolic acidosis with 
diabetic ketoacidosis.
• Glucosuria, normoglycemia, isosthenuria, 
or azotemia with renal tubular defects.
• Hypercalcemia with primary hyperpara- 
• Hypocalcemia with puerperal tetany.
• High serum alkaline phosphatase, 
proteinuria with hyperadrenocorticism.
• Panhypoproteinemia with intestinal 
• Serum fructosamine, ketone concentration—
to diagnose or rule out diabetes mellitus or 
diabetic ketoacidosis, respectively.
• Parathyroid hormone (PTH) assay—to 
diagnose or rule out hyperparathyroidism.
• PTH-related peptide (PTH-rp)—for 
hypercalcemia of malignancy.
• Vitamin D metabolite measurement—to 
diagnose or rule out vitamin D deficiency.
IMAGING
• Radiography may reveal urolithiasis in cases 
of primary hyperparathyroidism or poor bone 
quality/pathologic fractures with disorders of 
vitamin D metabolism.
• Ultrasonography or CT may reveal 
parathyroid mass.
Surgical exploration of the cervical area may 
reveal a parathyroid mass. Urine anion gap 
can reveal renal tubular secretory defect.
  TREATMENT
• Prevention is preferred.
• Asymptomatic patients with low (1.5–2.5 mg/
dL), but not depleted, phosphorus concen -
trations may not need phosphate treatment. 
Cats are more likely to have hemolysis with 
marked hypophosphatemia.
• If caused by insulin administration or 
hyperalimentation, administer supplemental 
• Severe hypophosphatemia ( <1.5 mg/dL)—  
patients need hospitalization and monitoring for 
hemolysis or hemolytic crisis. Administer isotonic 
crystalloid solution without calcium, IV, 
supplemented with potassium phosphate.
• Packed red blood cell transfusion for severe 
hemolytic crisis.

740  Blackwell’s Five-Minute Veterinary Consult  
• Phosphate—0.01–0.12 mMol/kg/h IV. 
Monitor serum phosphorus every 6–8 
hours.
◦ Potassium phosphate (3 mMol phosphate/
mL and 4.4 mEq potassium/mL) IV.
◦ Sodium phosphate (3 mMol phosphate/
mL and 4 mEq sodium/mL) IV.
• Discontinue therapy when serum phosphorus 
concentration reaches 2 mg/dL in order to 
avoid iatrogenic hyperphosphatemia and 
• Concurrent diuretic administration, 
especially carbonic anhydrase inhibitors.
• Iatrogenic hyperphosphatemia causes 
hypocalcemia and soft tissue (especially blood 
vessels) mineralization.
• Potassium phosphate may precipitate  
in IV line if coadministered with calcium-
containing fluids, dobutamine, fluoroquinolones.• Angiotensin-converting enzyme (ACE) 
inhibitor (e.g., enalapril) administration.
• Cardiac glycoside (e.g., digoxin) 
• Potassium-sparing diuretics (e.g., 
spironolactone).
Oral phosphate supplement (e.g., phospho-
soda) if not vomiting.
  FOLLOW-UP
• Measure serum phosphorus levels every 6–8 
hours until within normal range.
• Monitor patients for hyperphosphatemia 
and discontinue treatment immediately.
• Check serum potassium level daily until 
stable.
• Hemolysis.
• Respiratory depression and failure.
• Cardiac arrest.
Concurrent hypokalemia is common in 
patients with diabetic ketoacidosis.
Usually presents in older dogs.PREGNANCY/FERTILITY/BREEDING
Concurrent hypocalcemia in the periparturient 
animal increases PTH-promoted renal excretion 
of phosphorus, causing hypophosphatemia.
SEE ALSO
http://eclinpath.com/chemistry/minerals/
phosphate
• AMP = adenosine monophosphate.
• PTH-rp = PHT-related peptide.
of phosphorus: hypophosphatemia and 
hyperphosphatemia. In: DiBartola SP , ed., 
Fluid Therapy in Small Animal Practice, 
4th ed. Philadelphia, PA: Saunders, 2012, 
pp. 195–211.
Hooft KV, Drobatz KJ, Ward CR. 
Hypophosphatemia. Compend Cont Edu 
Vet 2005, 27:900–911.
and phosphate disorders. In: Silverstein DC, 
Hopper K. eds., Small Animal Critical Care 
Medicine, 2nd ed. St. Louis, MO: Elsevier 
Saunders, 2015, pp. 281–288.
Consulting Editor  Patty A. LathanHypophosphatemia  (continued)

Canine and Feline, Seventh Edition  741
HHypopituitarism
  BASICS
OVERVIEW
• A condition resulting from a defect in 
pituitary hormone synthesis; most frequently 
due to a genetic mutation.
• Associated with low production of pituitary 
hormones including thyroid-stimulating 
hormone (TSH), luteinizing hormone, 
follicle-stimulating hormone, and growth 
hormone (GH). Adrenocorticotropic 
hormone (ACTH) synthesis is usually 
preserved in dogs with congenital hyposomato -
tropism (pituitary dwarfism).
• Hypopituitarism due to transsphenoidal 
hypophysectomy to treat pituitary-dependent 
hypercortisolism can result in hypothyroidism, 
hypocortisolism, and possible GH deficiency.
• Dogs.
• Age—2–6 months.
• Breeds—German shepherd dog, Karelian 
bear dog, Saarloos wolfhound, spitz, 
miniature pinscher, and Weimaraner.
• Simple autosomal recessive in German 
shepherd dog and Karelian bear dog; 
mutation of the LHX3  gene.
SIGNS
• Mental retardation manifested as difficulty 
in housebreaking.
• Slow growth noticed in first 2–3 months of life.
• Proportionate dwarfism.
• Retained puppy hair coat.
• Thin, hypotonic skin.
• Shrill bark.
• T runcal alopecia.
• Cutaneous hyperpigmentation.
• Infantile genitalia.
• Delayed dental eruption.
• Mutation of LHX3  gene.
• Isolated GH deficiency.
Acquired
• Pituitary tumor.
• T rauma.
• Radiotherapy.
• Hypophysectomy.
  DIAGNOSIS
• Hypothyroid dwarfism.
• Portosystemic shunt, diabetes mellitus, 
hyperadrenocorticism, malnutrition, 
parasitism (all result in stunted growth).CBC/BIOCHEMISTRY/URINALYSIS
• GH and insulin-like growth factor (IGF) 
assays; GH assay not currently available in the 
United States; recommend measurement of 
IGF-1, which is low.
• Adrenal function is usually preserved in 
dogs with the LHX3  mutation.
• TSH response test; subnormal response to 
TSH.
• Ghrelin-stimulation test—monitors 
changes in GH levels in response to ghrelin; 
requires GH assay.
• DNA testing.
IMAGING
Radiography may reveal epiphyseal dysgenesis 
and abnormal retention of physeal growth 
plates.
  TREATMENT
Manage medically on an outpatient basis.
• GH—porcine GH, if available; has the 
same structure as canine GH: 0.1 IU/kg SC 
three times weekly for 4–6 weeks. Dose 
adjustments based on IGF-1 measurements 
every 4–6 weeks initially.
• The author is currently using the following 
source for porcine GH in the United States: 
http://www.humc.edu/hormones/material.
html. This is not an FDA-approved drug in 
any species and requires client consent and 
special preparation and handling by a 
veterinary pharmacist.
• Medroxyprogesterone acetate (2.5–5 mg/kg 
IM q3 weeks, then q6 weeks after normal 
stature is achieved).
• T reat hypothyroidism with levothyroxine 
(22 μg/kg PO q24h).
• Glucocorticoids (e.g., prednisone: 0.2 mg/kg 
PO q24h) if ACTH response test results are 
consistent with hypoadrenocorticism; higher 
dosage of steroids is needed during periods of 
stress.
Hypersensitivity reactions and carbohydrate 
intolerance may develop with growth 
hormone supplementation.  FOLLOW-UP
• IGF-1 every 4–6 weeks initially, and then 
less frequently.
• Blood and urinary glucose concentration.
• Stop GH supplementation if glucosuria 
develops or blood glucose is >150 mg/dL.
Acromegaly and diabetes mellitus; pyometra 
in female dogs treated with progestins.
• Skin and hair coat improve within 6–8 
weeks of initiating GH and thyroid 
• Generally no increase in stature because 
growth plates have usually closed by the time 
of diagnosis.
• Dogs often die at a young age (3–4 years) 
because of neurologic complications, renal 
failure, or infections.
• Poor long-term prognosis.
SEE ALSO
• IGF-1 = insulin-like growth factor-I.
Campbell KL. Growth hormone-related 
disorders in dogs. Compend Cont Educ 
Pract Vet 1988, 10:477–482.
Voorbij AMWY, Leegwater PA, Kooistra HS. 
Pituitary dwarfism in Saarloos and 
Czechoslovakian wolfdogs is associated with 
a mutation in LHX3. J Vet Int Med 2014, 
28(6):1770–1774.

742  Blackwell’s Five-Minute Veterinary Consult  
HHypopyon and Lipid Flare
  BASICS
OVERVIEW
Hypopyon
Accumulation of white blood cells in anterior 
chamber of eye; inflammatory breakdown of 
blood–aqueous barrier allows entry of cells 
into anterior chamber; chemoattractants 
mediate influx; cells settle in ventral anterior 
chamber due to gravity.
Lipid Flare
Resembles hypopyon but turbidity of anterior 
chamber is caused by lipids in aqueous 
humor; requires breakdown of blood–aqueous 
barrier and concurrent hyperlipidemia.
Dogs and cats; no age or sex predilection.
SIGNS
Hypopyon
• White to yellow opacity within anterior 
chamber—may be a ventral accumulation of 
cells or may completely fill anterior chamber; 
fibrin accumulation in anterior chamber may 
prevent discrete settling of white blood cells, 
resulting in cells suspended within fibrin 
matrix. • Concurrent ophthalmic signs 
include blepharospasm, epiphora, diffuse 
corneal edema, aqueous flare, miosis, iridal 
swelling, and vision loss.
• Diffuse milky appearance to anterior 
chamber. • Concurrent ophthalmic signs may 
include vision loss, mild blepharospasm, and 
mild to moderate diffuse corneal edema.
Hypopyon
Any cause of uveitis can result in hypopyon—
most commonly associated with severe uveitis. 
Hypopyon can also result from neoplastic cell 
accumulation in ocular lymphoma.
Lipid flare results from hyperlipidemia and 
concurrent uveitis; hyperlipidemia may also 
destabilize blood–aqueous barrier directly. 
Postprandial lipemia may occasionally result 
in lipemic aqueous if uveitis is present.
  DIAGNOSIS
Hypopyon
Fibrin in anterior chamber—generally forms 
an irregular clot, not ventral horizontal line.
• Severe aqueous flare—does not appear as 
milky white as lipid flare; animals with aqueous flare generally exhibit more ocular 
pain. • Diffuse corneal edema—severe 
corneal edema may be confused with anterior 
chamber opacity, but corneal stromal 
thickening, keratoconus, and corneal bullae 
are noted with the former.
Hypopyon
Often normal; abnormalities relate to 
underlying cause of uveitis.
Elevated serum triglycerides and cholesterol; 
abnormalities reflect underlying metabolic 
Hypopyon
None if hypopyon is related to obvious 
corneal disease; if related to uveitis, look for 
underlying cause of uveitis (e.g., anterior 
uveitis).
See Hyperlipidemia.
Anterior chamber centesis indicated with 
suspicion of neoplastic hypopyon; otherwise 
unrewarding.
  TREATMENT
• Hypopyon requires aggressive treatment for 
uveitis and underlying cause.
• Lipid flare requires treatment for uveitis 
and underlying metabolic disorder.
Hypopyon
• Topical —prednisolone acetate 1% or 
dexamethasone 0.1%: apply 2–6 times daily, 
depending on disease severity; taper 
medication as condition resolves. 
• Subconjunctival —triamcinolone acetonide 
(dog: 4–6 mg; cat: 4 mg) or 
methylprednisolone (dog: 3–10 mg; cat: 4 mg) 
by subconjunctival injection; one-time 
injection followed by topical and/or systemic 
anti-inflammatories. • Systemic —prednisone 
(dog: 0.5–2.2 mg/kg/day; cat: 1–3 mg/kg/
day); taper dose after 7–10 days; only if 
infectious causes of uveitis have been ruled out.
(NSAIDs)
• Topical— flurbiprofen, diclofenac, or 
kerorolac: 2–4 times daily, depending on severity of disease; less effective than 
corticosteroids. • Systemic— carprofen (dog: 
2.2 mg/kg PO q12h); meloxicam (dog: 
0.2 mg/kg PO q24h); robenacoxib (cat: 
1 mg/kg PO q24h; limit duration of use to 
3 days); meloxicam (cat: 0.2 mg/kg IV/SC/
PO once, then 0.05 mg/kg IV/SC/PO q24h 
for 2 days, then 0.025 mg/kg q24–48h; limit 
duration of use to 4 days); do not use 
NSAIDs concurrently with systemic 
Atropine sulfate 1%—1–4 times daily, 
depending on severity of disease; use 
ointment instead of solution in cats to 
minimize salivation.
Topical Corticosteroids
Prednisolone acetate 1% or dexamethasone 
0.1%—2–4 times daily, depending on 
severity of disease; taper medication as 
Atropine sulfate 1%—1–2 times daily, for 
ocular discomfort.
• Avoid topical miotic medications. • Topical 
and subconjunctival corticosteroids contraindi -
cated if ulcerative keratitis present. • Out of 
concern for secondary glaucoma, topical 
atropine should be used judiciously with 
intraocular pressure (IOP) monitoring.
  FOLLOW-UP
Recheck in 2–3 days. IOP should be monitored 
to detect secondary glaucoma. Frequency of 
subsequent rechecks dictated by response to 
• Hypopyon—prognosis guarded to good; 
to treatment. • Lipid flare—prognosis good; 
generally responds quickly (within 24–72 
hours) to moderate anti-inflammatory 
therapy; recurrence possible.
drug.

Canine and Feline, Seventh Edition  743
HHyporexia
  BASICS
OVERVIEW
• Spontaneous decrease in food intake, and 
implies inadequate caloric intake.
• T riggered by numerous conditions and 
reflects a derangement in hypothalamic 
processes that govern satiety and hunger.
• Prolonged hyporexia results in weight loss 
and contributes to sarcopenia and cachexia.
Dogs and cats of all ages; no breed or sex 
SIGNS
• Patients may refuse all food (anorexia) or 
consume a portion of their caloric needs.
• Preferential appetite may be reported for 
treats or highly desirable foods, but not a 
balanced diet.
• Signs suggesting nausea (e.g., drooling or 
gagging) may be reported, and severely 
affected animals may avoid food or try to 
hide it.
• Sustained hyporexia results in weight loss, 
and may be accompanied by a decrease in 
lean muscle mass as well as fat.
• Any metabolic derangement (endocrine, 
renal, hepatic) or organic compromise (e.g., 
respiratory or cardiovascular or gastro­
intestinal disease).
• Systemic inflammation (infectious, sterile, 
neoplastic).
• Medications, pain/discomfort, or 
psychologic issues (fear, anxiety).
• Lesions in the hypothalamus or affecting 
smell.
  DIAGNOSIS
Must be differentiated from ‘pseudo ­
inappetence’, i.e., limited intake due to oral 
pathology, prehension disorders or palatability 
issues.
• Influenced by underlying cause(s), but can 
be normal despite inadequate intake.
• Sustained and severe hyporexia in cats may 
result in hepatic lipidosis, characterized by an 
increase in alkaline phosphatase activity and 
As necessary to identify underlying cause(s).
IMAGING
As necessary to identify underlying cause(s).  TREATMENT
• Underlying disorders, vomiting/nausea, 
pain, and anxiety should be addressed 
promptly.
• Medications contributing to poor intake 
should be withdrawn if possible.
• Offering warmed food or more palatable 
options may be helpful.
• Sustained hyporexia should be addressed 
with an enteral feeding device (e.g., esopha­
geal feeding tube) or parenterally in patients 
with substantial gastrointestinal compromise.
• Numerous medications are anecdotally 
reported to improve food intake in companion 
animals, but most are not licensed for this 
purpose and there are limited efficacy and 
safety data.
• Practitioners are encouraged to use 
FDA ­approved appetite stimulants before 
considering alternative approaches.
• The administration of an appetite 
stimulant should not delay efforts to identify 
and address the underlying cause(s) of 
hyporexia.
• Capromorelin—dogs: 3 mg/kg PO q24h; a 
ghrelin receptor agonist, FDA ­approved as an 
appetite stimulant for dogs (feline product 
under development).
◦ Mimics actions of ghrelin, the “hunger 
hormone,” a peptide secreted by gastric 
mucosa.
◦ Receptors located in hypothalamus; 
activation promotes feelings of hunger and 
food­seeking behavior.
◦ Ghrelin also triggers release of growth 
hormone, increasing muscle mass and lean 
weight gain.
• Mirtazapine—dogs: 3.75–30 mg/dog PO 
q24h; cats: 1.9 mg/cat PO q48h; used 
off­label for many years as an appetite 
stimulant; mechanism is likely related to 
increased central norepinephrine levels. 
T ransdermal formulation approved for cats 
(2 mg/cat q24h).
• Mirtazapine has relatively narrow 
therapeutic window; should be dosed 
cautiously in small patients and those with 
renal compromise. Side effects can include 
vocalization, behavior changes, and tremors.
• Serotonin syndrome may occur with 
concurrent administration of monoamine 
oxidase inhibitors, metoclopramide, 
ondansetron, or tramadol.  FOLLOW-UP
Monitor food intake and bodyweight 
carefully, and modify therapy for both 
underlying disease and hyporexia as necessary.
Prompt recognition and management of 
conditions that may impact food intake.
• Cats with sustained, substantial hyporexia 
may develop hepatic lipidosis.
• Hyporexia impacts outcome and mortality 
in hospitalized people and it likely has a 
similar impact in companion animals.
• Response to appetite stimulants is variable; 
some animals require enteral feeding devices.
• Underlying cause(s) of hyporexia ultimately 
determines prognosis.
Sarcopenia (i.e., age ­related loss of muscle) 
and cachexia (i.e., rapid/extreme weight loss 
and muscle wasting) are associated with or 
exacerbated by hyporexia.
None (unless related to underlying cause).
• https://entyce.aratana.com
• https://kindredbio.com/
mirataz ­mirtazapine ­transdermal ­ointment
Rhodes L, Zollers B, Wofford JA, Heinen E. 
Capromorelin: a ghrelin receptor agonist and 
novel therapy for stimulation of appetite in 
dogs. Vet Med Sci 2017, 4(1):3–16.
Author  Audrey K. Cook

744  Blackwell’s Five-Minute Veterinary Consult  
HHyposthenuria
  BASICS
Urine specific gravity (USG) between 1.000 
and 1.006.
The ability to concentrate urine normally 
(dogs: >1.030; cats: >1.035) depends on a 
complex interaction between antidiuretic 
hormone (ADH), the protein receptor for 
ADH on the renal tubule, and a hypertonic 
renal medullary interstitium; interference 
with the synthesis, release, or actions of ADH, 
damage to the renal tubule, or altered tonicity 
of the medullary interstitium (medullary 
washout) can cause hyposthenuria.
Species
None
None
None
SIGNS
• Urinary incontinence—occasional.
disorder.
CAUSES
Any disorder or drug that interferes with the 
release or action of ADH, damages the renal 
tubule, causes medullary washout, or causes a 
primary thirst disorder (see Differential 
Diagnosis).
  DIAGNOSIS
• Central diabetes insipidus (little or no 
ADH produced).
• Nephrogenic diabetes insipidus (resistance 
to ADH).
• Primary liver disease.
• Primary polydipsia—compulsive water 
drinking.LABORATORY FINDINGS
Cortisone, lithium, demeclocycline, 
methoxyflurane, thiazide diuretics, and 
intravenous administration of fluids can all 
lower USG into the hyposthenuric range.
Yes
• Low USG (1.000–1.006); other 
abnormalities may point to the underlying 
cause.
enzyme activity suggests 
hyperadrenocorticism or primary liver disease.
• High cholesterol common in patients with 
• Leukocytosis with a left shift in some 
patients with pyometra or pyelonephritis.
• Low serum potassium concentration 
confirms hypokalemia.
• Inflammatory sediment or bacteriuria and 
positive urine culture consistent with 
• Proteinuria common in patients with 
pyelonephritis, pyometra, and hyperadreno  - 
stimulation test to screen for hyperadreno -
corticism and hypoadrenocorticism.
• Low-dose dexamethasone suppression test 
and urine : cortisol creatinine test to screen 
for hyperadrenocorticism.
• Serum bile acids concentration to evaluate 
liver function ( note: dogs with hyperadreno-
corticism often have mild elevations of bile 
acid concentration).
IMAGING
• Radiography to assess renal size and shape 
and to detect calcified adrenal tumor or large 
uterus.
• Ultrasonography to assess adrenal size, renal 
and hepatic size and architecture, and uterine 
size. Dilated renal pelves may indicate 
pyelonephritis or be an artifact of IV fluid 
therapy.
• MRI or CT may identify pituitary or 
hypothalamic mass that may be the cause of 
central diabetes insipidus or hyperadreno- 
• Desmopressin response test to differentiate 
primary central diabetes insipidus from 
primary nephrogenic diabetes insipidus.
• Reassessment of USG following change of 
environment in a dog suspected of having 
primary polydipsia. For example, some dogs 
hospitalized with free access to water will drink less and concentrate urine by the end of 
the day, suggesting a diagnosis of primary 
polydipsia.
  TREATMENT
• Depends on the underlying disorder.
• Do not restrict patient’s water intake unless 
appropriate to the definitive diagnosis.
Depend on the underlying disorder.
  FOLLOW-UP
USG, hydration status, renal function, and 
Dehydration
See Differential Diagnosis.
None
SEE ALSO
DiBartola SP . Fluid, Electrolyte and 
Practice, 3rd ed. Philadelphia, PA: 
Saunders, 2005.

Canine and Feline, Seventh Edition  745
HHypothermia
  BASICS
Due to limited clinical literature in veterinary 
science, much of the information below has 
been extrapolated from human medical 
literature and experimental animal studies.
• Core body temperature drops below that 
required for normal metabolism. In primary 
hypothermia, the healthy individual’s 
compensatory responses to heat loss are 
overwhelmed by exposure, whereas secondary 
hypothermia complicates many systemic diseases. 
• Stage I—90–95 °F (32–35 °C). • Stage 
II—82–90 °F (28–32 °C). • Stage III—75–82 °F 
(24–28 °C). • Stage IV— <75 °F (24 °C).
• Normal thermoregulation balances heat 
gained or lost to the environment with heat 
produced via central thermogenesis; it is 
controlled by the hypothalamus with input 
from thermoreceptors; heat can be gained or 
lost to the environment via four mechanisms: 
evaporation, radiation, convection, and 
conduction; central thermogenesis generates 
heat via basal metabolism, muscle activity, and 
uncoupling of brown fat (neonates). • Heat 
production can be augmented via shivering 
and increased basal metabolic rate; activation 
of both sympathetic nervous and endocrine 
systems results in increased circulating levels of 
thyroid-releasing hormone, catecholamines, 
growth hormone, and glucocorticoids, which 
all contribute to increased glucose utilization 
and basal metabolic rate. • Adaptations to 
minimize heat loss include cutaneous 
vasoconstriction, piloerection, and behavioral 
responses such as curling up, sharing body 
heat, and seeking shelter.
• Cardiovascular—in mild hypothermia, 
sympathetic stimulation induces tachycardia 
and peripheral vasoconstriction with normal or 
elevated cardiac output (CO) and BP; as the 
patient becomes colder, cardiac pacemaker cell 
depolarization is slowed, resulting in 
bradycardia resistant to treatment with 
atropine; the resultant fall in CO is balanced by 
increased systemic vascular resistance; at lower 
temperatures, bradycardia becomes 
progressively extreme and systemic vascular 
resistance falls as catecholamine release and 
adrenergic receptor responsiveness are blunted. 
• Endocrine—sympathetic activation and 
release of counter-regulatory hormones trigger 
increased glycogenolysis, gluconeogenesis, and 
lipolysis as well as inhibit the release and uptake 
of insulin resulting in hyperglycemia; when 
hypothermia develops slowly or is longlasting, 
glycogen stores become depleted and 
hypoglycemia develops. • Gastrointestinal—
increased gastric acid production and reduced duodenal bicarbonate secretion may predispose 
to gastrointestinal ulceration; ileus is common. 
• Hemic—plasma shifts and consequent 
hemoconcentration may lead to hyper- and 
hypocoagulopathy; depressed enzymatic activity 
of clotting factors and platelet hyporeactivity 
may exacerbate hypocoagulability. 
• Hepatobiliary/pancreatic—hypoxia leads to 
hepatocellular damage and pancreatitis. 
• Musculoskeletal—increased joint fluid 
viscosity and muscle stiffness. • Nervous—
CNS metabolism and level of consciousness 
decrease and nerve conduction velocity 
progressively slows; mild incoordination is 
followed by lethargy, obtundation, and coma. 
• Renal—peripheral vasoconstriction increases 
renal blood flow and glomerular filtration rate 
resulting in increased urine production; 
progressive tubular dysfunction and antidiuretic 
hormone resistance contribute further to cold 
diuresis; later, urine output decreases as result of 
falling CO; acute kidney injury may ensue. 
• Respiratory—initial tachypnea replaced by 
decreased respiratory rate and tidal volume and 
increased airway secretions; as temperature falls, 
protective airway reflexes are reduced; below 
93.2 °F (34 °C) ventilatory drive is attenuated 
and increased pulmonary vascular resistance 
leads to ventilation–perfusion mismatch; 
progressive hypoventilation, apnea, and, more 
rarely, pulmonary edema may develop; 
hypothermia shifts the oxyhemoglobin 
dissociation curve to the left; this may be 
masked by concurrent lactic and respiratory 
acidosis that may become so profound the 
overall result is a right shift. • Skin—edema 
secondary to increased vascular permeability.
GENETICS
Unknown
Varies with geographic location.
Most common in cold climates.
Species
Smaller breeds with increased surface area.
More common in neonates and geriatrics.
None
SIGNS
A thorough search should be made to find 
precipitating, comorbid conditions.
• Known prolonged exposure to cold ambient 
temperatures. • Possibly, disappearance from 
home or a history of trauma.Physical Examination Findings
Stage I: 90–95  °F (32–35  °C)
• Lethargy and weakness. • Vigorous 
shivering (variable). • Variable heart rate, 
rhythm, and BP . • Light pink to pale mucous 
membranes. • Confusion, agitation, or 
obtundation. • Variable respiratory rate.
STAGE II: 82–90 °F (28–32 °C)
• Collapse. • Reduced shivering (variable). 
• Bradyarrhythmia with hypotension. • Pale 
mucous membranes. • Muscle and joint 
stiffness. • Obtundation, stupor, or coma. 
• Ataxia and hyporeflexia. • Reduced depth 
and rate of respiration.
STAGE III: 75–82 °F (24–28 °C)
• Moribund with cold, edematous skin. • Loss 
of shivering (variable). • Bradyarrhythmia with 
hypotension. • Pale mucous membranes. 
• Muscle and joint stiffness. • Coma with 
fixed, dilated pupils. • Areflexia. • Reduced 
depth and rate of respiration or respiratory 
arrest. • Pulmonary edema.
STAGE IV: <75 °F (<24 °C)
• No vital signs. • Cardiac arrest.
CAUSES
• Inadequate thermogenesis: ◦ Normal 
thermogenesis is overwhelmed. ◦ Serious 
illness. • Extreme heat loss: ◦ Excessive 
evaporation, conduction, convection, and 
radiation. ◦ Inability to vasoconstrict blood 
vessels or piloerect hair. ◦ Loss of behavioral 
adaptations. • Thermoregulatory center 
failure: ◦ Hypothalamic injury or disease.
• Extremes of age. • Low body fat and 
glycogen stores. • Burn injury. • Intracranial 
injury or disease. • Hypothyroidism. 
• Diabetic ketoacidosis. • Sepsis. • T rauma. 
• General anesthesia. • Medications 
including but not limited to beta blockers, 
barbiturates, narcotics, phenothiazines.
  DIAGNOSIS
• Primary CNS disease, hypoglycemia, 
anemia, hepatic encephalopathy, myxedema, 
electrolyte disturbances, sepsis, intoxication, 
neoplasia, and death. • Bradyarrhythmia—
cardiac disease, medication side effects, and 
• Results depend on severity and presence of 
comorbidities. • CBC—hemoconcentration, 
leukopenia, and thrombocytopenia. 
• Biochemistry—azotemia, hyper- and 
hypoglycemia, variable electrolyte 
abnormalities, elevated liver enzyme activity, 
hyperbilirubinemia. • Urinalysis—
isosthenuria and glucosuria.

746  Blackwell’s Five-Minute Veterinary Consult  
• Blood gas—variable; metabolic and 
respiratory acidosis is common. 
• Hyperlactatemia—shivering, reduced tissue 
perfusion, and impaired hepatic clearance. 
• Coagulation—hyperfibrinogenemia and 
disseminated intravascular coagulation; in vivo 
prolongation of clotting times may not be 
reflected by in vitro assays and should correct 
with rewarming. • Thyroid hormone evaluation 
may confirm underlying hypothyroidism.
IMAGING
To investigate recovery complications or 
comorbid conditions.
ECG
Classic findings include presence of Osborn 
or J-waves, atrial and ventricular dysrhyth-
mias, and prolongation of PR, QRS, and QT 
intervals with progression from sinus 
bradycardia through atrial fibrillation to 
ventricular fibrillation and ultimately asystole.
• Findings in patients who succumb to 
primary hypothermia are variable and 
nonspecific; if body cooling and death occur 
rapidly, necropsy findings are minimal but 
may include reddish discoloration of skin, 
hemorrhagic gastric erosions, and lipid 
deposits in epithelial cells of renal proximal 
tubules and other organs. • Patients who die 
from secondary hypothermia may have similar 
findings; however, they will also have evidence 
of a separate and significant disease process.
  TREATMENT
Emergency inpatient intensive care until 
normothermic and stable.
• Warming: ◦ Active external rewarming using 
warm blankets, heating pads, radiant heat, forced 
warm air, and administration of warm parenteral 
fluids (stage II) is used in patients with stage I–II 
hypothermia; complications include core 
temperature after-drop whereby return of cold 
blood from periphery to central circulation 
causes further core cooling; rewarming of the 
trunk should be performed before the extremities 
to minimize this risk. ◦ Techniques to warm 
patients with stage III–IV hypothermia include 
administration of warm humidified oxygen, 
warmed IV fluids, and bladder or gastric lavage 
with warm saline; more invasive and technically 
demanding methods include closed thoracic and 
peritoneal lavage, and extracorporeal rewarming. 
◦ Whole-body immersion in hot water is 
contraindicated, as it will cause massive 
vasodilatation and hypotension and is likely to 
provoke dysrhythmias and cardiovascular 
collapse. • Fluid therapy: ◦ IV crystalloid fluids warmed to 104 °F (40 °C). ◦ During rewarming, 
these patients have significant IV fluid 
requirements as vasoconstriction relaxes and cold 
diuresis is reversed. ◦ Patients must be closely 
monitored for volume overload during 
resuscitation. • Consider inotropic drugs in 
patients unresponsive to volume resuscitation. 
• Mechanically ventilate patients with 
respiratory failure.
ACTIVITY
Minimally affected patients should be 
encouraged to be active, as muscle activity 
will generate more endogenous body heat.
DIET
Withhold oral intake until patient is alert.
Prevention of exposure to cold temperatures is 
imperative in preventing primary hypothermia. 
Clients with very young and very old patients as 
well as those with serious medical conditions or 
taking medications that inhibit thermoregulatory 
ability should be counseled to keep their pets 
indoors and to take protective measures if they 
are to be exposed to cold temperatures.
N/A
• Hypoglycemic patients warrant dextrose 
supplementation. • Antiarrhythmic agents 
generally not warranted as most arrhythmias 
will resolve with rewarming.
No evidence to support routine use of 
steroids or antibiotics.
Systemic clearance of metabolized drugs is 
slowed proportionally—consider dose 
reduction to minimize likelihood of 
unanticipated toxicity.
N/A
N/A
  FOLLOW-UP
• Continuous core body temperature. 
• Continuous ECG and frequent BP during 
rewarming. • Frequent assessment (q6–12h) 
of electrolytes, acid-base status, packed cell 
volume, total protein, and blood glucose. 
• Daily monitoring of blood urea nitrogen, 
urine specific gravity, coagulation indices, and 
liver enzymes in severely affected patients.PREVENTION/AVOIDANCE
• Avoid prolonged exposure to cold. • Monitor 
and maintain body temperature in anesthetized 
animals.
• Peripheral vasodilation during rewarming may 
further drop BP and body temperature. 
• Iatrogenic burns. • Return of cool peripheral 
blood to the heart may precipitate cardiac 
arrhythmias. • Cardiac arrest. • Gastric lavage 
increases the risk of aspiration pneumonia and 
fluid and electrolyte shifts. • Thoracic and/or 
peritoneal lavage increases the risk for 
hemorrhage, lung or bowel trauma, and fluid and 
electrolyte shifts. • Extracorporeal rewarming 
techniques have increased risk for local vascular 
complications, air embolism, hypotension, 
hemorrhage, thrombosis, and hemolysis.
Variable—depend on severity, underlying 
cause, and patient health status.
None
Sick or hypoglycemic neonates can become 
markedly hypothermic in normal environ- 
ments.
N/A
N/A
SYNONYMS
None
SEE ALSO
Shock, Cardiogenic.
• CO = cardiac output.
Brodeur A, Wright A, Cortes Y. Hypothermia 
and targeted temperature management in 
cats and dogs. JVECC 2017, 
27(2):151–163.
Brown DJA, Brugger H, Boyd J, Paal P . 
Accidental hypothermia. NEJM 2012, 
367:1930–1980.
Paal P , Gordon L, Strapazzon G, et al. 
Accidental hypothermia – an update. 
Scand J T rauma Resusc Emerg Med 2016, 
24:111–130.
Author  Gretchen L. Schoeffler
available onlineHypothermia  (continued)

Canine and Feline, Seventh Edition  747
HHypothyroidism
  BASICS
Clinical manifestations that result from 
inadequate production of thyroxine (T4) and 
3,5,3 ′-triiodothyronine (T3) by the thyroid 
gland. Characterized by a generalized decrease 
in cellular metabolic activity.
Acquired Hypothyroidism
• In dogs, acquired hypothyroidism can be 
primary, secondary, or tertiary.
• Primary hypothyroidism is associated with 
a defect localized to the thyroid gland. The 
thyroid tissue has been destroyed or replaced 
and thus becomes less responsive to thyroid-
stimulating hormone (TSH). T3 and T4 levels 
gradually decline, with a compensatory 
increase in TSH.
◦ Lymphocytic thyroiditis is an immune-
mediated process characterized by chronic 
and progressive lymphocytic infiltration 
and destruction of the thyroid gland. This 
process is gradual and accounts for the slow 
onset of clinical signs associated with 
hypothyroidism. The immune-mediated 
process is associated with production of 
autoantibodies, predominantly against 
thyroglobulin; however, autoantibodies 
against T3 and T4 have been reported.
◦ Idiopathic thyroid atrophy does not 
demonstrate an inflammatory component 
and is caused by the replacement of normal 
thyroid tissue with adipose tissue.
◦ Together, these processes account for 
95% of the clinical cases of hypothyroidism 
in dogs; each accounts for 50% of reported 
cases.
◦ Rare causes of primary hypothyroidism 
include neoplastic destruction of thyroid 
tissue, iodine deficiency, infection, and 
iatrogenic destruction secondary to drugs, 
surgery, or radioiodine treatment.
• Secondary acquired hypothyroidism is rare. 
The defect is localized to the pituitary, where 
the ability to synthesize and secrete TSH is 
impaired. Secondary hypothyroidism may be 
caused by pituitary tumors, congenital 
malformation of the pituitary, infection, or 
TSH suppression. Drugs, hormones, or 
concurrent illness can cause TSH suppression.
• Tertiary hypothyroidism (not reported in 
the veterinary literature) is hypothalamic in 
origin, and production of thyrotropin-
releasing hormone (TRH) is either decreased 
or nonexistent.
• Hypothyroidism may occur following 
radioactive iodine (I-131) therapy for 
hyperthyroidism in cats.
Congenital Hypothyroidism
• Congenital hypothyroidism is a rare disease 
that is categorized as goitrous or nongoitrous. Goiter (enlargement of the thyroid gland) 
develops when there is increased release of 
TSH, along with an intact thyroid TSH 
receptor.
• An autosomal recessive form of congenital 
hypothyroidism has been reported in specific 
dog and cat breeds. Affected animals have a 
thyroid peroxidase deficiency.
• Congenital hypothyroidism is also noted as 
an element of panhypopituitarism.
• Nervous.
GENETICS
• No known genetic basis for heritability 
associated with adult-onset primary 
hypothyroidism in dogs, although some 
breeds appear to be predisposed to thyroiditis.
hypothyroidism has been reported in toy fox 
terriers, giant schnauzers, Tenterfield terriers, 
and Abyssinian cats.
• Primary hypothyroidism is the most 
common endocrinopathy in dogs. Prevalence 
appears to average about 1 : 250.
• Hypothyroidism is rare in cats.
Worldwide
Species
Larger-breed dogs are more likely to develop 
hypothyroidism (golden retriever, Doberman 
pinscher, Great Dane, Irish setter), though 
several smaller-breed dogs do appear to also 
be predisposed (miniature schnauzer, cocker 
spaniel, poodle, dachshund).
Most commonly seen in middle-aged dogs, 
with the average age of onset being 7 years.
None
SIGNS
Clinical signs associated with hypothyroidism 
are vague and involve many different systems.
• Lethargy, weight gain, and hair loss are the 
most common signs (40–50% of all cases).
• Pyoderma (often recurrent), hyperpig -
mentation of the skin, and a dry, brittle hair 
coat (10% of cases).• Rarely ( <5% of cases), facial paralysis, 
weakness, or conjunctivitis.
• Most changes appear to be secondary to 
decreased metabolism due to a lack of 
circulating thyroid hormones.
• The most common findings include 
dermatologic abnormalities (88% of 
hypothyroid dogs):
◦ Bilateral symmetric nonpruritic truncal 
alopecia; hair loss is noted in areas of 
increased wear and usually includes the 
ventral thorax and neck, ventral abdomen, 
elbows, and tail. Loss of primary hair is 
most common, with retention of guard 
hairs, resulting in a short, fine hair coat.
◦ Dry, lackluster hair coat.
◦ Seborrhea is common and may be 
localized or have a more generalized 
distribution pattern.
◦ Pyoderma is noted in 14% of 
hypothyroid dogs and may be recurrent in 
nature. Generalized demodicosis and 
Malassezia  spp. infections are common. 
Though primary dermatologic conditions 
are nonpruritic, pruritis may accompany 
secondary parasitic, yeast, or bacterial 
infections. Chronic changes to the skin can 
result in thickening and hyperpigmentation.
• Decreased activity/lethargy.
• Most neurologic signs are associated with 
polyneuropathy and include weakness, facial 
nerve paralysis, vestibular signs (usually 
peripheral), and hyporeflexia. No data support 
a direct association between megaesophagus or 
laryngeal paralysis and hypothyroidism.
• CNS signs, including seizures, ataxia, and 
coma (myxedema coma), are rare.
• In females, hypothyroidism is associated 
with increased periparturient mortality and 
lower birth rate in pups. In males, decreased 
fertility has been reported, but not confirmed, 
in hypothyroid dogs.
• Cardiovascular abnormalities are rare. 
Bradycardia, arrhythmias, decreased 
conduction, decreased contractility, and 
diastolic dysfunction have been reported.
• Ocular changes including corneal 
cholesterol deposits, keratoconjunctivitis sicca 
(KCS), and conjunctivitis are seen in less than 
1% of hypothyroid dogs.
• Lethargy and general inactivity.
• Dwarfism.
• Constipation (more common in cats).
CAUSES
• Lymphocytic thyroiditis.
• Idiopathic thyroid atrophy.
• Pituitary disease.
• Congenital abnormalities.

748  Blackwell’s Five-Minute Veterinary Consult  
H• Iodine deficiency (dietary).
• Iatrogenic (secondary to surgery or radiation).
• Surgical removal (bilateral) of the thyroid 
gland.
• I-131 therapy for hyperthyroidism in cats.
  DIAGNOSIS
• Primary dermatologic disease.
• Other endocrinopathies (hyperadreno -
corticism, diabetes mellitus, growth hormone 
• Hepatobiliary disease.
• Useful to rule out nonthyroidal illness.
• Normochromic, normocytic, and 
nonregenerative anemia is a common finding 
(28–32% of hypothyroid dogs).
• Hypercholesterolemia (present in over 75% 
of hypothyroid dogs).
• Hypertriglyceridemia.
• Elevated levels of cholesterol and triglyce -
rides have been associated with atherosclerosis 
in dogs, although this is rare.
• No specific changes are noted on urinalysis.
• Diagnosing hypothyroidism is complex. 
The TSH stimulation test is a reliable single 
test used to diagnose hypothyroidism and is 
considered the gold standard. However, there 
is limited access to test reagents and the cost 
is often prohibitive.
• Several tests are available to assess thyroid 
function, thyroid hormone levels, and 
antithyroglobulin antibody levels. These tests 
include total T4, free T4, endogenous TSH, 
antithyroglobulin antibodies, anti-T3 
antibodies, anti-T4 antibodies, total T3, 
reverse T3, and free T3.
• Combination testing will yield a reliable result.
Total T4
• Initial screening (high sensitivity) test of 
thyroid function.
• This test measures both protein-bound and 
free T4 levels.
• The test is a direct assessment of the ability 
of the thyroid gland to produce hormone.
• A decreased total T4 level is a common finding 
in hypothyroid animals, but is not diagnostic of 
hypothyroidism as concurrent illness can cause 
an artificial decrease in total T4 level.
Free T4
• Measures metabolically active portion of 
total T4 level.
• Hypothyroid animals would be expected to 
have a low free T4 level.• Concurrent illness has less effect on the free 
T4 level compared with the total T4 level.
• Measurement by equilibrium dialysis 
(fT4ED) has been demonstrated to be more 
reliable than radioimmunoassay, because it 
mitigates the influence of antithyroglobulin 
• Newer methods of free T4 analysis utilize 
chemiluminescent technology with compara -
ble sensitivity and specificity to fT4ED, but 
the effect of antibodies on this assay is unclear, 
and the fT4ED is still the gold standard.
Endogenous TSH Level
• Measurement of canine endogenous TSH is 
• Cross-reactivity allows this assay to be used 
in cats; however, it may be accurate only 50% 
of the time in cats.
• This test has high specificity and low 
sensitivity; best used as a confirmatory test 
and not as a screening test.
• TSH level is expected to be elevated in 
primary hypothyroid animals due to loss of 
negative feedback, however, 20–40% of 
hypothyroid dogs have TSH values in the 
reference range.
• Interpretation of the TSH level requires 
knowledge of the total or free T4 level.
• Methods of assessing TSH levels are less 
sensitive at low levels and evaluation of 
endogenous TSH cannot be used to diagnose 
secondary hypothyroidism.
Antithyroglobulin Antibodies
• Antithyroglobulin antibodies include 
antithyroglobulin, anti-T3, and anti-T4 
• A positive titer is predictive of immune-
mediated thyroiditis, and suggestive of 
hypothyroidism, but only 20% of euthyroid 
dogs with antibodies develop hypothyroidism 
within 1 year.
• Anti-T3 and -T4 antibodies are similar to 
T3 and T4 and can cross-react to falsely 
elevate these assay levels. In animals who 
are slightly hypothyroid (as measured by 
total T4), the presence of anti-T4 antibodies 
may make it appear as if these animals are 
euthyroid, leading to a delay in the 
diagnosis and treatment of hypothyroidism.
TSH Stimulation Test
• Historically considered the gold standard 
for diagnosing hypothyroidism.
• Pharmaceutical-grade bovine TSH was used 
to conduct this test; however, this is no longer 
• Recombinant human TSH can be used 
safely in both dogs and cats to effectively 
conduct the test, but is expensive. Therefore, 
this test is unlikely to become routine.
Total T3, Reverse T3, and Free T3
• Total T3 measurement is an unreliable 
indicator of thyroid function.
• The total T3 level has been demonstrated to 
be normal in up to 90% of hypothyroid dogs.• The reverse T3 level has not been validated 
in companion animals.
• Evaluation of total T3, reverse T3, and free 
T3 levels is not recommended to assess 
Nonthyroid Factors That Alter Thyroid 
Function T ests
• In addition to sick euthyroid syndrome, other 
factors alter the results of thyroid function tests, 
which may result in a misdiagnosis.
• Most nonthyroid factors cause an artificial 
decrease  in thyroid hormone levels.
• Some drugs can decrease thyroid hormone 
levels, but do not usually result in an animal 
developing clinical signs of hypothyroidism. 
Glucocorticoids, phenobarbital, and nonsteroi -
dal anti-inflammatory drugs (NSAIDs) can 
decrease circulating thyroid hormone levels.
• Sulfonamides can decrease thyroid 
hormone levels and lead to clinical disease. 
This effect is noted to occur within weeks of 
initiation of therapy and disappears 2 weeks 
after therapy has been discontinued.
• Glucocorticoids inhibit the entire 
hypothalamic-pituitary-thyroid axis and have 
a direct effect against thyroid hormone.
• Phenobarbital causes a decrease in thyroid 
levels only in animals receiving long-term 
treatment. Phenobarbital should not be 
administered for 4 weeks prior to thyroid 
• The influence of NSAIDs is variable and 
evaluation of thyroid function should be 
made with caution, and preferably after 
stopping NSAIDs well in advance of testing.
• Well-conditioned and athletic dogs 
consistently have lower total and free T4 levels. 
Certain breeds have normal ranges of thyroid 
hormones that are different from other breeds. 
The greyhound, Scottish deerhound, saluki, 
and whippet have total T4 concentrations that 
are well below the mean concentrations for 
other dogs. Alaskan sled dogs have serum T4, 
T3, and free T4 concentrations below the 
normal reference range.
• Vaccination causes a transient increase in 
circulating autoantibody levels, which may 
cause a truly hypothyroid animal to appear 
euthyroid. Thyroid function testing should 
not be conducted if a patient has been 
vaccinated within the previous 2 weeks.
IMAGING
Developmental bone problems (delayed 
epiphyseal ossification or dysgenesis) are 
usually noted with congenital 
• Significant differences in thyroid gland 
volume and echogenicity exist between 
hypothyroid and euthyroid patients, but 
interpretation is highly user dependent.
• No significant difference is noted between 
euthyroid and sick euthyroid subjects.Hypothyroidism  (continued)

Canine and Feline, Seventh Edition  749
HPATHOLOGIC FINDINGS
• Lymphocytic thyroiditis is characterized by 
chronic and progressive lymphocytic 
infiltration and destruction of the thyroid 
gland. Cytotoxic T cells initiate inflammation, 
leading to thyrocyte destruction and 
parenchymal fibrosis.
• Idiopathic thyroid atrophy is characterized by 
the replacement of normal thyroid parenchyma 
with adipose and connective tissue.
• Many cutaneous changes are nonspecific. 
However, certain findings, including dermal 
thickening, myxedema, and vacuolation of 
arrector pili muscles, are most characteristic.
  TREATMENT
Outpatient medical management.
• Lifelong therapy required.
• Easily managed with oral thyroid hormone 
• Dose adjustments are common in the early 
• Most clinical signs will resolve over time with 
appropriate thyroid hormone supplementation.
• Synthetic thyroid hormone supplementation 
easily treats hypothyroidism.
• Levothyroxine sodium is available as both 
human and veterinary products.
• Generic forms of the drug should be 
avoided, as human studies have demonstrated 
wide variability in the bioavailability of 
generic forms. If a generic form is used, 
always prescribe the same formulation.
• Hormone supplementation is initiated at 
0.02 mg/kg PO q12h.
• Supplementation can often eventually be 
decreased to once daily after proper control is 
achieved.
• Levothyroxine doses for dogs exceed those 
for humans and may confuse pharmacists or 
human endocrinologists.
• Humans are instructed to take the medica -
tion on an empty stomach and proton pump 
inhibitors can impede absorption. This should 
be considered if a dog is difficult to regulate.
Patients with concurrent metabolic conditions 
(hepatic disease, endocrinopathies, renal 
disease, cardiac disease) should have 
supplementation started slowly (about 25% 
of recommended dose) and slowly increased 
over time (3 months) to the recommended 
maintenance level.POSSIBLE INTERACTIONS
• Glucocorticoids, NSAIDs, furosemide may 
increase metabolism of levothyroxine.
• GI protectants can decrease absorption and 
administration should be separated from 
thyroid hormone supplementation by 2 hours.
• If T4 levels do not normalize after 
attempting monitoring and treatment, 
treatment can be attempted with liothyronine 
(4–6 mg/kg PO q8–12h).
• Monitoring is based on T3 levels. However, 
there is no reliable method by which to 
measure T3.
  FOLLOW-UP
• Assessment of clinical signs, weight, and 
thyroid function testing is recommended 6–8 
weeks after therapy has begun, 2–4 weeks after 
each dose change, and then once to twice 
yearly. Patients should also be monitored if 
signs of thyroid toxicosis (e.g., polyuria/
polydipsia [PU/PD], polyphagia) occur.
• The total T4 level should be monitored and 
timed so that blood is taken 4–6 hours after 
pill administration.
• Once stable and well controlled, the total 
treatment dose may be given once daily in 
some dogs.
• For animals receiving supplementation once 
daily, blood should be taken immediately 
before the medication is given and then again 
4–6 hours later, to measure trough and peak 
• When supplementation therapy is approp -
riate, the total postdose T4 level should be in 
the upper half of the reference range, or 
slightly above it.
• If the total T4 level is significantly increased 
above normal, the medication dose should be 
decreased or the frequency of administration 
reduced.
• If the total T4 level is low, an increase in the 
dose may be necessary.
• Before increasing dose, assess client 
compliance, evaluate GI status to ensure there 
is no impact on absorption, and confirm 
there has been no change in the levothyroxine 
formulation.
Adequate hormone supplementation with 
routine monitoring should avoid recurrence 
of this condition.
• If untreated hypothyroid animals are 
at increased risk of developing  
myxedema, myxedema coma, and 
atherosclerosis.
• Oversupplementation of thyroid hormone 
can result in iatrogenic hyperthyroidism.EXPECTED COURSE AND  
PROGNOSIS
• Primary hypothyroidism can be easily and 
successfully controlled; the prognosis for affected 
animals, when appropriately treated, is excellent. 
Resolution of clinical signs is an important 
predictor of adequate supplementation therapy.
• Significant improvement in attitude, 
activity level, and alertness should occur 
within 1 week of starting therapy.
• Dermatologic abnormalities improve 
slowly, with complete resolution taking up to 
3 months.
• Polyneuropathies usually begin improving 
quickly; complete resolution may take several 
months.
• Anemia and serum cholesterol levels 
gradually resolve in the first weeks of therapy.
• Life expectancy usually normal.
• Congenital hypothyroidism has a guarded 
to poor prognosis.
May rarely be associated with other 
endocrinopathies.
Increased periparturient mortality and lower 
birthweight pups.
SEE ALSO
Myxedema and Myxedema Coma
• fT4ED = Free T4 measured by equilibrium 
dialysis.
• I-131 = radioactive iodine.
Bellumori TP , Farnula TR, Bannasch DL, 
et al. Prevalence of inherited disorders 
among mixed-breed and purebred dogs; 
27,254 cases (1995–2010). J Am Vet Assoc 
2013, 242(11):1549–1555.
Scott-Moncrieff JCR. Hypothyroidism. In: 
Veterinary Internal Medicine, 7th ed. St. 
Louis, MO: Elsevier, 2010, pp. 1751–1761.
available online(continued)  Hypothyroidism

H750  Blackwell’s Five-Minute Veterinary Consult  
HHypoxemia
  BASICS
• A decrease in partial pressure of arterial 
oxygen (PaO2), resulting in marked 
desaturation of hemoglobin.
• PaO2 at sea level ranges from 80 to 
100 mmHg in normal animals.
Six physiologic causes:
(PIO2).
• Hypoventilation (increase in partial 
pressure of carbon dioxide in arterial blood 
[PaCO2]).
• Mismatching of alveolar ventilation and 
perfusion so that areas of the lung that are not 
ventilated properly are still perfused adequately.
• Alveolar–capillary membrane diffusion defect.
• Right‐to‐left cardiac or pulmonary shunting.
• All organs—oxygen essential for normal 
cellular function; individual tissue oxygen 
requirements vary by organ.
• Cardiovascular—can result in focal or 
global ischemia; if prolonged, can develop 
arrhythmias and cardiac failure.
• Nervous—brain and CNS most important; 
hypoxemia can result in irreversible brain 
damage because there are no large oxygen 
stores in brain tissue.
SIGNS
• Breathing problems—especially open‐
mouth breathing.
• T rauma.
• Episodes of coughing.
• Gagging.
• Dyspnea.
• Orthopnea.
• Coughing.
• Open‐mouth breathing.
• Poor peripheral pulse.
• Abnormal thoracic auscultation.
CAUSES
• Low PIO2—high altitude (the higher the 
elevation, the lower the barometric pressure, 
which results in a decrease in PIO2; fraction of oxygen in inspired air (FIO2) is fixed at 
0.21); suffocation; enclosure in small areas 
with improper ventilation.
• Hypoventilation—result of inadequate 
alveolar ventilation; muscular paralysis; upper 
airway obstruction; air or fluid in the pleural 
space; restriction of the thoracic cage, 
diaphragmatic hernia; CNS disease; 
anesthetics.
perfusion—most common cause of 
hypoxemia and occurs with virtually any lung 
disease: pulmonary thromboembolism; 
pulmonary parenchymal disease (infectious or 
neoplastic); lower airway disease; pneumonia; 
pulmonary contusions; pulmonary edema; 
also during anesthesia or prolonged 
recumbency when a large region of lung 
becomes atelectatic.
• Alveolar–capillary membrane diffusion 
impairment—rarely clinically important.
• Right‐to‐left cardiac or pulmonary 
shunting—tetralogy of Fallot; ventricular 
septal defect; reversed patent ductus arteriosus; 
intrapulmonary arteriovenous shunt.
• Move to higher elevation.
• T rauma.
• Bronchopneumonia of any cause.
• Bronchial disease—chronic bronchitis, 
feline asthma.
• Diseases associated with risk of emboli­
zation, e.g., immune‐mediated hemolytic 
anemia, hyperadrenocorticism, neoplasia, 
pancreatitis, sepsis.
  DIAGNOSIS
• Signs of tachypnea and/or dyspnea.
• Excitement or anxiety.
• Pyrexia.
• Head trauma.
• Pain.
N/A
Results
• Air bubbles in the arterial blood sample—
falsely high PaO2 values.
• Improper packaging of the arterial blood 
sample—falsely high PaO2 values after 
approximately 30 min at room temperature.Valid if Run in Human Laboratory?
Yes
• Packed cell volume (PCV)—can be high 
with chronic condition; can be low if 
inflammatory or neoplastic.
• Liver enzyme elevation common with organ 
hypoxia.
Arterial Blood Gases
• Collect arterial blood sample in an 
anaerobic manner, as follows: use enough 
the syringe; collect sample from femoral or 
dorsal pedal artery; place a rubber stopper 
on the needle or covering the hub of the 
syringe, to prevent room air from entering 
the sample; analyze sample within 15 min 
if left at room temperature; place sample 
on ice to extend safe time for analysis to 
2–4 hours.
IMAGING
Thoracic radiographs and 
echocardiography— evaluate intrathoracic 
disease; differentiate pulmonary and cardiac 
disease.
Pulse Oximetry
• Indirectly determines saturation of arterial 
blood with oxygen (SaO2); relation between 
PaO2 and SaO2 based on oxyhemoglobin 
dissociation curve: SaO2 >90% when PaO2 
>60 mmHg.
• SaO2 <95%—considered abnormal, 
indicates PaO2 <80 mmHg.
• Best results when probe used on animal’s 
tongue; thus may be limited to anesthetized, 
heavily sedated, or seriously ill patients with 
low level of consciousness; keep tongue 
moistened for most accurate readings.
• Other potentially successful probe sites—
lip, ear; vulva (female), prepuce (male); skin 
between toes; thin skin in the flank area. 
Interpret values with caution.
• Poor results—using sites that have hair or 
poor perfusion; least accurate in low‐flow 
states such as hypotension (global low flow) 
or hypothermia (low flow to skin); falsely low 
values (usually <85%) during carboxyhemo­
globinemia (smoke inhalation).
• Rectal probes will allow readings in awake 
patients.
Endoscopy or Lung Biopsy
Airway sampling often required to 
determine primary abnormality resulting 
in hypoxemia.

Canine and Feline, Seventh Edition  751
HH  TREATMENT
Must identify and correct the primary cause.
Oxygen Therapy
• Most common supportive treatment.
• Corrects low‐inspired oxygen, hypoventil­
ation, and alveolar–capillary membrane 
diffusion defects; may not fully correct 
mismatching of ventilation and perfusion; 
does not correct right‐to‐left cardiac or 
pulmonary shunts and low cardiac output.
• May not be completely beneficial until 
adequate blood volume is established or 
alveolar contents are removed (e.g., 
pulmonary edema, purulent material).
• Delivery—directly from an oxygen source 
from the anesthetic machine via a face mask 
placed securely around the muzzle or from an 
E‐tank fitted with an oxygen regulator 
through a face mask, intranasal catheter 
placed in the oropharynx, or oxygen cage.
• Increase in FIO2—determined by the 
oxygen flow rate and the amount of oxygen 
mixed with room air.
• Positive pressure ventilation—may be 
needed for severe hypoxemia of any cause.
• High flow oxygen therapy (HFOT) has 
been shown to increase arterial oxygen in 
dogs with severe hypoxemia.
Fluid Therapy
• Low cardiac output—fluid administration 
and inotropic support (e.g., pimobendan, 
dobutamine, or dopamine) important.
• Cardiac failure—requires aggressive medical 
treatment; diuretics; afterload and preload 
reduction; inotropic support; oxygen 
administration; cautious amounts of fluids 
may be indicated after institution of primary 
treatment; use caution with type and rate of 
fluids after initial stabilization.
• Hypovolemic, hemorrhagic, traumatic, or 
septic shock—requires end point fluid 
administration; crystalloids (20–30 mL/kg), 
hypertonic solutions (7% NaCl, 4 mL/kg), 
or blood products (packed red blood cells 
[pRBC], whole blood, plasma), or a 
combination.
• Severe pulmonary contusion—hypertonic 
fluids or low dose crystalloids (5–10 mL/kg).  MEDICATIONS
For bronchospasm—bronchodilators; 
terbutaline (0.01 mg/kg SC/IM/IV q8h) or 
albuterol inhaler.
• Aggressive fluid administration—not 
indicated for cardiac failure and pulmonary 
edema.
• Diuretics—not indicated for shock, low 
PIO2, alveolar–capillary membrane 
diffusion defects, mismatching of alveolar 
ventilation and perfusion, and right‐to‐left 
shunts.
• Inotropic drugs—arrhythmias may develop.
• Oxygen toxicity—prolonged ( >12 hour) 
exposure to high‐concentration ( >70%) 
oxygen can result in pulmonary edema, 
seizures, and death.
N/A
  FOLLOW‐UP
• Decrease in respiratory effort and decrease 
in cyanosis (if initially noted)—check efficacy 
of treatment and support.
• Arterial blood gas—determine resolution.
• Pulse oximetry—alternative; interpret results 
cautiously with hypotension, hypothermia, 
smoke inhalation, and non‐tongue probe site. 
T rend in the actual number being produced is 
• Brain damage—depends on severity and 
duration of hypoxemia; partial or complete 
loss of neuronal function; dementia; seizures; 
loss of consciousness.
• Arrhythmias—may develop secondary to 
myocardial hypoxia; may be very difficult to 
treat effectively.
• Respiratory arrest requiring intubation and 
positive pressure ventilation.  MISCELLANEOUS
N/A
N/A
May adversely affect fetuses, especially during 
first trimester of pregnancy.
SEE ALSO
• FIO2 = fraction of oxygen in inspired air.
• HFOT = High flow oxygen therapy.
• PaO2 = partial pressure of arterial oxygen.
• PIO2 = partial pressure of inspired oxygen.
• pRBC = packed red blood cells.
• SaO2 = saturation of arterial blood with oxygen.
Guenther CL. Oxygen therapy. In: Drobatz 
KJ, Hopper K, Rozanski E, Silverstein DC. 
Textbook of Small Animal Emergency 
Medicine. Ames, IA: Wiley‐Blackwell, 
2019, pp. 1177–1182.
Haskins SC. Hypoxemia. In: Silverstein DC, 
Hooper K, eds. Small Animal Critical Care 
Medicine. St. Louis, MO: Elsevier 
Saunders, 2015, pp. 81–86.
Wiley‐Blackwell, 2015, pp. 102–108.
Mazzaferro EM. Oxygen therapy. In: 
Silverstein DC, Hooper K, eds. Small 
MO: Elsevier Saunders, 2015, pp. 77–80.
Analgesia, 5th ed. Ames, IA: Wiley‐
Consulting Editor  Elizabeth Rozanski(continued)  Hypoxemia

752  Blackwell’s Five-Minute Veterinary Consult  
IIcterus
  BASICS
Increased total bilirubin concentration 
causing yellow tissue discoloration.
• Bilirubin—derived from degradation of 
heme-containing proteins; most (80%) from 
senescent erythrocytes; remainder from other 
heme-containing proteins (e.g., P450 
cytochromes, myoglobin). • Unconjugated 
bilirubin—transported in plasma bound to 
albumin; diglucuronide conjugated after 
hepatocellular uptake. • Conjugated bilirubin—
transported in bile, expelled into intestines where 
most converted to other products, e.g., 
urobilinogen can undergo enterohepatic 
circulation, stercobilin colors feces brown. 
• Hyperbilirubinemia—caused by increased 
bilirubin production (increased red blood cell 
[RBC] destruction; hemolytic jaundice ); heme 
exceeding hepatic capacity for uptake, 
conjugation, or biliary excretion ( hepatic 
jaundice ), or interrupted biliary elimination 
(posthepatic jaundice ). • Nonhemolytic jaundice 
caused by hepatobiliary disease or bile peritonitis.
• Skin/exocrine—skin discoloration 
(jaundice) reflects serum bilirubin >2.5 mg/
dL. • Hepatobiliary—retained bile acids and 
markedly increased bilirubin may contribute 
to hepatocellular injury. • Renal/urologic—
extreme hyperbilirubinemia may cause renal 
tubular injury. • Nervous—extreme 
unconjugated hyperbilirubinemia may cause 
degenerative brain lesions (rare, kernicterus).
Species
• Most causes—diseases of adult animals. 
• Young, unvaccinated dogs—at risk for 
infectious canine hepatitis.
Adult female pure-bred dogs—at risk for 
immune-mediated hemolytic anemia.
SIGNS
Increased Formation: Hemolysis
• Vague signs—lethargy, weakness. 
• Gastrointestinal (GI) signs—anorexia, 
constipation, vomiting, weight loss. • Jaundice. 
• Recent blood transfusion. • Severe trauma—
bleeding into muscle, abdomen, or hematoma 
formation. • Rhabdomyolysis (rare cause).
Decreased Elimination: Cholestasis
• Vague GI signs—anorexia, vomiting, 
diarrhea, change in fecal color: nonobstructive 
jaundice green, orange; obstructed jaundice 
acholic. • Jaundice. • Change in urine color—orange. • Abdominal enlargement—if 
ascites. • Polyuria and polydipsia. • Altered 
mentation—if hepatic encephalopathy (HE).
• Pallor, tachycardia, tachypnea, weakness, 
bounding femoral pulses, anemic heart murmur. 
• Jaundice. • Hepatomegaly/splenomegaly—
extramedullary hematopoiesis, reticuloen -
dothelial hyperplasia. • Lymphadenopathy. 
• Bleeding tendencies—if thrombocytopenic. 
• Orange feces. • Fever. • “Gelatinous” feel to 
skin (vasculopathy). • Rhabdomyolysis—
weakness, pain.
• Weight loss. • Jaundice. • Hepatomegaly/
splenomegaly. • Abdominal effusion/mass/pain. 
• Melenic, orange, green, or acholic feces. • Fever.
CAUSES
Prehepatic Jaundice
• Hemolytic disorders—immune-mediated 
hemolysis; certain drugs (propylene glycol 
carriers in cats, trimethoprim sulfa); systemic 
lupus erythematosus; infectious disorders; toxins 
(e.g., oxidative injury: zinc, onions; phenols); 
severe hypophosphatemia. • Incompatible 
blood transfusion. • Infections—feline leukemia 
virus (FeLV); Mycoplasma haemofelis ; heartworm; 
Babesia ; Ehrlichia ; Cytauxzoon . • Large-volume 
blood resorption—hematomas, body cavities 
(e.g., hemangiosarcoma, warfarin).
Hepatic Jaundice
• Chronic idiopathic or familial hepatitis. 
• Adverse drug reactions—e.g., anticonvul -
sants; acetaminophen; trimethoprim sulfate; 
carprofen; stanozolol (cats); benzodiazepines 
(cats); see Hepatotoxins. • Cholangitis/
cholangiohepatitis. • Infiltrative neoplasia—
lymphoma. • Cirrhosis (dogs). • Hepatic 
lipidosis (cats). • Massive liver necrosis—e.g., 
aflatoxin, cycad, nonsteroidal anti-inflamma -
tory drugs (carprofen), copper associated injury. 
• Systemic illnesses with hepatic involve -
ment—leptospirosis (dogs); histoplasmosis; 
feline infectious peritonitis; hyperthyroidism 
(cats); toxoplasmosis (cats). • Bacterial 
sepsis—originating anywhere in body; may 
elaborate bacterial products that impair hepatic 
bilirubin processing/elimination.
Posthepatic Jaundice
T ransient or persistent mechanical bile duct 
obstruction—pancreatitis (transient obstruction); 
neoplasia: bile duct, pancreas, duodenum; 
intraluminal duct occlusion: cholelithiasis, 
sludged bile, liver flukes (cats), immune-  
mediated duct destruction (sclerosing cholangitis 
in cats), gall bladder mucocele (dogs); ruptured 
biliary tree causing bile peritonitis.
• Young unvaccinated dogs—infectious disease, 
canine infectious hepatitis. • Breed predisposition 
for familial hepatic disease—Labrador retriever, 
Doberman pinscher, Bedlington terrier, cocker spaniel, Dalmatian. • Middle-aged, obese 
dogs—pancreatitis. • Anorectic, obese cats—
hepatic lipidosis. • Hepatotoxic drugs. • Blunt 
abdominal trauma, chronic biliary tract disease, 
gallbladder mucocele—bile peritonitis. 
• Hemolytic anemia.
  DIAGNOSIS
• Prehepatic jaundice—usually abrupt onset; 
mucous membrane pallor; mild to moderate 
jaundice; weakness; tachypnea; cardiac 
murmur with severe anemia. • Hepatic 
jaundice—breed risk for familial hepatitis; 
variable jaundice; otherwise normal mucous 
membranes; alteration in liver size (large or 
small); abdominal effusion (pure or modified 
transudate); polyuria and polydipsia; 
behavioral abnormalities of HE; coagulopathy. 
• Posthepatic jaundice—chronic and/or 
recurrent bouts of apparent GI signs or 
pancreatitis with cholelithiasis; moderate or 
marked jaundice; otherwise normal mucous 
membranes; diffuse or cranial abdominal pain; 
cranial abdominal mass; abdominal effusion 
(septic, nonseptic, or bile peritonitis); bleeding 
tendencies; acholic feces unless melena.
• Bilirubin assay—based on diazo reaction; 
assesses direct-reacting and total serum 
bilirubin; most yield reasonable total bilirubin 
results; values for direct bilirubin vary. 
• Higher readings in heparinized plasma. 
• Sample management—important; total 
bilirubin may decrease by 50% per hour with 
direct exposure to sunlight or artificial lighting. 
• Hemolysis—variable effects on total 
bilirubin measured by spectrophotometry. 
• Lipemia—falsely increases total bilirubin 
values measured by endpoint assays. 
• Fractionation into conjugated and 
unconjugated— unable to define causes of 
jaundice , contrary to dogma.
• CBC—severe anemia (usually regenerative); 
blood smear may reveal autoagglutination, 
spherocytes, Heinz bodies, parasites; hemo -
globinemia with intravascular hemolysis, 
normal to low platelets, normal to high 
WBCs, with left shift. • Biochemistry— 
normal to high alanine aminotransferase 
(ALT) and alkaline phosphatase (ALP) 
activity, blood urea nitrogen (BUN) concen -
tration; normal to low albumin; normal to 
high globulin; normal glucose and cholesterol; 
high bilirubin.
• CBC—mild nonregenerative anemia; low 
mean corpuscular volume (MCV) with chronic 
liver disease and portosystemic shunting; variable

Canine and Feline, Seventh Edition  753
Iwhite blood cell (WBC) count. • Biochemistry—
mildly to markedly high ALT ± ALP; normal to 
low albumin, BUN, glucose, cholesterol. 
• Urinalysis—normal to dilute urine; 
bilirubinuria precedes hyperbilirubinemia; 
bilirubinuria important in cats.
• CBC—± mild nonregenerative anemia; 
variable WBC count. • Biochemistry—
increased ALT, moderate to markedly increased 
ALP; usually normal albumin, BUN, glucose 
concentrations; normal to high cholesterol.
• In-saline autoagglutination slide test—with 
suspected RBC agglutination; may have 
reported high MCV. • Direct Coombs’ test—
submit if no evidence of autoagglutination. 
• Osmotic fragility test—detects likelihood of 
RBC hemolysis tonicity challenge. • Blood 
smears—hemoparasites, spherocytes, schisto -
cytes, anisocytosis (regenerative). • Plasma 
zinc—if hemolytic anemia. • Antinuclear 
antibodies—with hemolytic anemia. • Serum 
bile acids—redundant if nonhemolytic 
jaundice already suspected. • Serology—for 
infectious diseases (e.g., FeLV, leptospirosis, 
mycoses) with signs of multisystemic illness and 
hepatic jaundice. • PCR for acute leptospiro -
sis—within first few days, urine and/or serum; 
before appropriate antibiotic therapy. 
• Abdominal effusion—characterize cell and 
protein content. • Coagulation tests—pro -
longed values, esp. proteins invoked by vitamin 
K absence or antagonism and prothrombin 
time, with bile duct occlusion; vitamin K1 
responsive. • Microbial culture and sensitiv -
ity—blood ± other specimens if inflammatory 
leukon and suspected bacterial infection (e.g., 
urinary tract, biliary tract, liver).
IMAGING
• Abdominal radiography—obscured by 
effusion; may reveal hepatomegaly, mass 
effect, mineral or gas interface in liver 
(emphysematous cholecystitis, choleliths); 
splenomegaly (hemolytic anemia, portal 
hypertension, abdominal neoplasia); 
metallic foreign body with zinc-induced 
hemolysis. • Thoracic radiography—may 
reveal metastatic disease; sternal lymphadeno -
pathy (reflecting abdominal disease); general 
lymphadenopathy (lymphosarcoma, 
systemic infection [fungal]). • Abdominal 
US—may distinguish parenchymal liver 
disease from extrahepatic biliary obstruc -
tion; characterizes hepatic parenchymal 
lesions; may disclose abdominal neoplasia; 
may determine cause of abdominal effusion; 
used to target lesions, fluid, or cystocentesis 
sampling (aspirates or needle biopsy).
• Fine-needle aspiration—cytology of mass, 
lymph node, hepatic parenchyma, bile. 
• Liver biopsy—bacterial culture of liver, bile, 
other specimens obtained via celiotomy, blind percutaneous, keyhole, laparoscopic, or 
US-guided techniques. • Surgical 
intervention—required for diagnosis and 
treatment of posthepatic disorders.
  TREATMENT
• Depends on underlying cause. 
• Inpatient—for initial medical care. • Cage 
rest—to facilitate liver regeneration or reduce 
oxygen requirements if severe anemia. 
• Diet—important for hepatic and 
posthepatic jaundice; nutritionally balanced 
with maximum protein tolerated; carbohy -
drate based (dogs) with restricted protein for 
hepatic encephalopathy; restrict sodium if 
ascites. • Vitamin supplementation— 
water-soluble vitamins in all patients; 
parenteral vitamin K1 for bile duct 
obstruction or severe cholestasis.
• Prehepatic jaundice—eliminate inciting 
cause; see Anemia, Immune-Mediated; whole 
blood transfusion for life-threatening anemia. 
• Hepatic/posthepatic jaundice—treat specific 
disorders based on imaging, biopsy, culture.
• Avoid known hepatotoxic drugs. • Avoid 
tetracyclines unless clearly indicated—suppress 
hepatic protein synthesis, promote hepatic 
lipidosis. • Avoid analgesics, anesthetics, 
barbiturates—with hepatic failure.
• Sedatives—may precipitate HE. 
• Corticosteroids—for nonseptic inflamma-
tion; increase risk for infection; may aggravate 
ascites (water and sodium retention), promote 
vacuolar hepatopathy (dogs) and hepatic 
lipidosis (cats).
Consider influence of altered hepatic 
metabolism on drug therapy; hypoalbuminemia 
influences potency of protein-bound drugs, 
enhancing effects (may lead to toxicity).
  FOLLOW-UP
• Prehepatic jaundice—recheck packed cell 
volume and blood smears as needed; may 
require repeat transfusions; taper immuno-
suppressive drugs. • Hepatic and posthepatic 
jaundice—recheck serum biochemical profile 
as dictated by underlying disease; continue symptomatic and specific treatments until 
remission, varies with disease process.
• Patients with immune-mediated hemolysis 
treated with immunosuppressive doses of 
corticosteroids predisposed to thromboembolism, 
GI ulcers, and infection. • Patients in hepatic 
failure susceptible to infections, enteric 
bleeding, ascites. • Patients with reconstructive 
biliary surgery have risk of recurrent bacterial 
cholangitis.
SYNONYMS
Jaundice
SEE ALSO
• Copper Associated Hepatopathy. 
• Liver Fluke Infestation.
alanine aminotransferase. • BUN = blood 
urea nitrogen. • FeLV = feline leukemia virus. 
• GI = gastrointestinal. • HE = hepatic 
encephalopathy. • MCV = mean corpuscular 
volume. • RBC = red blood cell. • WBC = 
white blood cell.
Willard MD, T wedt DC. Gastrointestinal, 
pancreatic, and hepatic disorders. In: 
Willard M, Tvedten H, eds., Small Animal 
5th ed. St. Louis, MO: Saunders, 2012, pp. 
212–214.
Consulting Editor  Kate Holan 
available online(continued)  Icterus

754  Blackwell’s Five-Minute Veterinary Consult  
IIdioventricular Rhythm
  BASICS
If conduction of sinus node pacemaker 
impulses to the ventricles is blocked or the 
impulses decrease in frequency, the lower 
regions of the heart automatically take over 
the role of pacemaker for the ventricles, 
which results in ventricular escape complexes 
(Figure 1) or an idioventricular rhythm 
(Figure 2).
• P waves may be absent or may precede, be 
hidden within, or follow the ectopic QRS 
complex.
• P waves are unrelated to the QRS 
• QRS configuration—wide and bizarre; 
similar to that of a ventricular premature 
complex.
• May be hemodynamically important with 
slow ventricular rates.
• Does not occur in healthy animals.
• Subsidiary pacemakers seem to discharge 
more rapidly in cats than in dogs.
GENETICS
N/A
Unknown
Species
• Atrial standstill in English springer spaniels 
and Siamese cats.
• Pugs, miniature schnauzers, and 
Dalmatians prone to conduction 
N/A
N/A
SIGNS
• Some animals asymptomatic.
• Syncope.
• Irregular rhythm associated with pulse 
deficits.
• Variation in heart sounds.• Possible intermittent “cannon” waves in the 
jugular venous pulses (with atrioventricular 
[AV] block).
CAUSES
• Not a primary disease—a secondary result 
of a primary disease.
• The escape rhythm is a safety mechanism to 
maintain cardiac output.
Causes of Sinus Bradycardia and Sinus 
Arrest
• Increased vagal tone (high intracranial 
pressure, high ocular pressure).
• Drugs—digoxin, tranquilizers, propranolol, 
quinidine, and anesthetics.
• Addison’s disease.
Causes of AV Block
• Congenital.
• Lyme disease.
N/A
  DIAGNOSIS
• A series of ventricular escape beats with a 
heart rate <65 bpm in dogs and <100 bpm in 
cats; heart rates of 65–160 bpm in dogs and 
100–180 bpm in cats are often termed 
accelerated idioventricular rhythms.
• Ventricular tachycardia—dogs have a 
cardiac rate >160 bpm; cats >180 bpm.
• Slow heart rate in animals with right 
bundle branch block, left bundle branch 
block, or left anterior fascicular block; 
animals with these disturbances have the P 
waves associated with the QRS complexes.
• No specific findings.
• Complete blood testing may suggest a 
metabolic abnormality.
• Drug toxicity.
• Lyme titer in animals with complete 
AV block.
IMAGING
Echocardiogram may show structural heart 
disease.
ECG
Depend on underlying cause.  TREATMENT
• Rhythm is an escape or safety mechanism 
for maintaining cardiac output; do not direct 
treatment toward suppressing this escape 
rhythm, but toward the primary disease 
process that allows the escape rhythm to 
assume pacemaker control of the heart.
• Symptomatic treatment is directed toward 
increasing the heart rate.
May be required for underlying disease.
ACTIVITY
Symptomatic animals may require cage rest.
DIET
No modifications or restrictions unless 
required for management of the underlying 
Inform of the need to seek and specifically 
treat an underlying cause.
Pacemaker implantation may be necessary.
• Atropine or glycopyrrolate usually indicated 
to block vagal tone or increase the heart rate.
• If those drugs are ineffective, isoproterenol, 
dopamine, dobutamine, or artificial pacing 
may be needed.
Lidocaine, procainamide, quinidine, 
propranolol, diltiazem, or any other drug that 
slows the cardiac rate or reduces contractility.
Atropine is briefly vagotonic immediately 
post injection and can temporarily exacerbate 
the condition.
N/A
N/A
  FOLLOW-UP
• Serial ECG may show clearing of the 
lesion or progression to complete heart 
block.
• Serial blood profiles may be needed to monitor 
progress of the primary disease process.

Canine and Feline, Seventh Edition  755
I
• Serial echocardiograms may show improve-
ment or progressive changes in cardiac 
structure.
N/A
• Arrhythmia may abate when the primary 
disorder is corrected.
• Guarded if condition is associated with 
cardiac or metabolic disorder; poor if the rate 
is not increased pharmacologically or if 
underlying cause cannot be identified and 
treated.  MISCELLANEOUS
N/A
N/A
SEE ALSO
• Atrial Standstill.
Degree).
Kittleson MD, Kienle RD, eds. Small 
MO: Mosby, 1998, pp. 72–94.Santilli R, Moïse NS, Pariaut R, Perego M. 
Sleeper MM, eds. Manual of Canine and 
Tilley LP , Smith FWK, Jr. Essentials of 
Canine and Feline Electrocardiography: 
Interpretation and T reatment, 4th ed. 
Ames, IA: Wiley-Blackwell, 2021 (in 
preparation).
Figure 1 .
Ventricular escape complexes (arrows) during various phases in the dominant sinus rhythm in a dog during anesthesia. 
The sinus rate increased (not shown) after anesthesia was stopped; ½ cm–1 mv. (Source: From Tilley LP . Essentials of 
Canine and Feline Electrocardiography, 3rd ed. Baltimore, MD: Williams & Wilkins, 1992. Reprinted with permission 
of Wolters Kluwer.)
Figure 2.
Complete heart block. The P waves occur at a rate of 120, independent of the ventricular rate of 50. The QRS 
 configuration is a right bundle branch block pattern. The heart rate and QRS shape suggest that the rescuing focus is 
probably near the AV junction. (Source: From  Tilley LP . Essentials of Canine and Feline Electrocardiography, 3rd ed. 
Baltimore, MD: Williams & Wilkins, 1992. Reprinted with permission of Wolters Kluwer.)(continued)  Idioventricular Rhythm

756  Blackwell’s Five-Minute Veterinary Consult  
IIleus
  BASICS
OVERVIEW
• Adynamic (paralytic, functional) ileus is 
defined as a transient and reversible intestinal 
obstruction resulting from inhibition of 
bowel motility.
• Lack of peristalsis of stomach, small bowel, or 
large bowel causes functional obstruction, as 
intestinal contents accumulate in the dependent 
areas of the gastrointestinal tract instead of 
being propelled in an aborad direction.
• Ileus is not a primary disease but a 
secondary complication of a number of 
• Adynamic ileus is thought to occur 
secondary to electromechanical dissociation 
of the intestinal musculature due to increased 
sympathetic tone, release of humoral 
inhibitory factors (catecholamines, 
vasopressin, endogenous opiates), impaired 
release of prokinetic hormones (neurotensin, 
motilin), or hypokalemia.
• Secondary causes of intestinal pseudo-
obstruction have been subclassified into 
developmental, infectious, inflammatory, 
autoimmune, metabolic, paraneoplastic, 
endocrine, and toxic etiologies.
• Lymphocytic leiomyositis represents a 
visceral myopathic form of chronic intestinal 
pseudo-obstruction that has been described in 
humans, dogs, horses, and cats; it is defined 
as lymphocytic infiltration of the muscularis 
propria and is thought to represent an auto -
immune response to the myofibers of the 
muscularis propria layer of the bowel by T 
• Systems affected—gastrointestinal; 
autonomic nervous system.
SIGNS
• Coughing secondary to aspiration 
pneumonia from gastroesophageal reflux.
• Mild abdominal distention or discomfort 
secondary to accumulation of gas in 
hypomotile bowel.
• Failure to auscultate gut sounds after 2–3 
minutes suggests ileus.
• Gut sounds can be increased during initial 
state (partial loss of motility).
• Surgery (especially gastrointestinal surgery).
• Pain.
• Electrolyte imbalance (hypokalemia, 
hypomagnesemia, hypocalcemia).• Acute inflammatory lesions of bowel, 
peritoneal cavity, pancreas, or other 
abdominal organs.
• Unrelieved mechanical obstruction.
• Intestinal ischemia.
• Gram-negative sepsis.
• Shock.
• Retroperitoneal injury.
• Uremia.
• Autonomic neuropathies (dysautonomia, 
spinal cord injury).
• Visceral myopathies associated with 
autoimmune disease.
• Use of anticholinergic drugs.
• Intestinal overdistension (aerophagia).
• Lead poisoning.
• Stress (cold and noise).
  DIAGNOSIS
Adynamic ileus must be differentiated from 
mechanical obstruction caused by:
• Intestinal foreign bodies.
• Intramural abscess.
• Incarcerated or strangulated hernia.
• Volvulus.
• Mesenteric infarction.
• Adhesions.
• Postoperative stricture.
• Impaction.
• Congenital malformation.
• Inflammatory or traumatic lesions.
• Hemogram changes depend on primary 
cause of ileus.
• Serum chemistry profiles and urinalysis 
help assess electrolyte disturbances 
(especially hypokalemia) and presence of 
azotemia.
• Measurement of pancreatic lipase concent -
ration (Spec or SNAP cPL or fPL) to assess 
for pancreatitis.
• Fecal parvovirus ELISA test in puppies with 
ileus and diarrhea.
IMAGING
• Stomach and/or intestinal loops are 
distended with gas and fluid.
• Common radiographic patterns include:
◦ Generalized gas ileus—consider 
aerophagia, smooth muscle paralyzing 
drugs, generalized peritonitis, or enteritis.
◦ Generalized fluid ileus—consider 
enteritis, diffuse intestinal neoplasia.◦ Localized gas ileus—consider localized 
peritonitis (pancreatitis), early bowel 
obstruction, disruption of arterial supply.
◦ Localized fluid ileus—consider foreign 
body, neoplastic obstruction, intussusception.
• Differentiate adynamic ileus from 
mechanical intestinal obstructions.
• Identify pancreatitis or peritonitis.
• Ultrasound has been used to assess frequency 
and contraction of pyloric antrum in dogs.
• Careful evaluation of intestinal layers for loss 
of normal layering associated with infiltrative 
neoplasia, thickening of muscularis propria layer 
and/or submucosal layer associated with 
inflammatory bowel disease or small cell 
lymphoma, and attenuation of muscularis layer 
associated with fibrosis secondary to leiomyositis.
Barium-Impregnated Polyethylene 
Spheres (BIPS)
• Confirm adynamic ileus.
• Delayed gastrointestinal transit along with 
retention of BIPS in the stomach.
• Scattering of BIPS throughout the upper 
gastrointestinal tract.
Upper Gastrointestinal Series
• Upper gastrointestinal series can be 
performed to help assess for presence of 
partial intestinal obstructions or delayed 
gastric and intestinal motility.
• Gastric and intestinal transit times must be 
interpreted cautiously following administration 
of liquid barium in light of marked variation 
in emptying times from animal to animal, and 
the stress of hospitalization can delay gastric 
and intestinal transit times.
Other Procedures to Consider
• Noninvasive electrogastrography is used 
experimentally to assess gastric myoelectrical 
activity in dogs.
• Abdominocentesis with peritoneal effusion 
to confirm peritonitis.
• Gastrointestinal endoscopy or exploratory 
laparotomy to rule out mechanical obstruction.
• Full-thickness intestinal biopsies are 
necessary to diagnose intestinal leiomyositis 
because the disorder affects the muscularis 
propria layer of the bowel, which is typically 
not accessible via endoscopic biopsy.
• Spinal radiographs, myelogram, spinal 
MRI, CT, cerebrospinal fluid (CSF) analysis 
to identify spinal cord injury.
• Ocular response test with 0.1% pilocarpine 
and 0.25% physostigmine for dysautonomia.
  TREATMENT
• Identify and treat primary underlying cause.
• Correct electrolyte abnormalities (especially 
hypokalemia) if present.

Canine and Feline, Seventh Edition  757
I• Use of prokinetic drugs such as cisapride, 
metoclopramide, or erythromycin should be 
considered, depending on underlying cause.
• Gastrointestinal decompression of stomach 
via nasogastric tube is beneficial in select 
cases.
• Fat-restricted diets should be implemented 
in dogs with delayed gastric emptying because 
higher-fat diets can delay gastric emptying in 
this species.
• Metoclopramide is most effective when 
administered as CRI (1–2 mg/kg/24h); 
bolus injections (0.4 mg/kg IV q6h) are less 
effective in light of relatively short half-life 
(90 min) in dogs; metoclopramide does not 
affect colonic motility and should be 
avoided in animals with colonic ileus or 
• Cisapride (0.5–0.75 mg/kg q8–12h) is a 
far more potent and effective prokinetic 
compared to metoclopramide and affects 
gastric, small intestinal, and colonic 
motility.
• Erythromycin (1–2 mg/kg PO q12h) has 
prokinetic activity in stomach and small 
intestine.
• Cyclosporine (5 mg/kg q12–24h) can be 
administered for management of intestinal 
leiomyositis or other immune-mediated 
disorders affecting intestinal tract.
• Prednisone (1 mg/kg q12h with progressive 
tapering over 10–12 weeks) can be administered 
for management of leiomyositis or inflamma -
tory bowel disease.CONTRAINDICATIONS/POSSIBLE 
• Anticholinergic drugs (e.g., atropine, 
glycopyrrolate).
• Opiates (e.g., morphine, hydromorphone, 
oxymorphone, butorphanol).
• Opiate antidiarrheals (e.g., paregoric, 
diphenoxylate hydrochloride/atropine sulfate, 
loperamide hydrochloride).
  FOLLOW-UP
• Monitor and correct electrolyte imbalance 
• Abdominal auscultation to evaluate 
gastrointestinal motility.
• Survey abdominal radiographs to evaluate 
gastric and intestinal distension.
Avoid anticholinergic drugs and opiates if not 
Animals with adynamic ileus are predisposed 
to development of intestinal dysbiosis, 
bacterial translocation, and sepsis.
Prognosis depends on successful resolution of 
primary disease process.
SYNONYMS
• Adynamic ileus—functional ileus, paralytic 
ileus.• Pseudo-obstruction—chronic, more 
segmental adynamic ileus.
• Mechanical ileus—generally addressed in 
current literature as mechanical obstruction.
Ileus has been reported in a lactating bitch 
with hypomagnesemia and hypocalcemia.
• BIPS = barium-impregnated polyethylene 
spheres.
• CSF = cerebrospinal fluid
Choi M, Seo M, Jung J, et al. Evaluation of 
canine gastric motility with 
ultrasonography. J Vet Med Sci 2002, 
64(1):17–21.
Couraud L, Jermyn K, Yam PS, et al. 
Intestinal pseudo-obstruction, lymphocytic 
leiomyositis and atrophy of the muscularis 
externa in a dog. Vet Rec 2006, 
159(3):86–87.
Guilford WG. Motility disorders of the 
bowel. In: Guilford WG, Center SA, 
Strombeck DR, et al. Strombeck’s Small 
Animal Gastroenterology, 3rd ed. 
Philadelphia, PA: Saunders, 1996, 
pp. 335–336.
Novellas R, Simpson KE, Gunn-Moore DA, 
Hammond GJ. Imaging findings in 11 cats 
with feline dysautonomia. J Feline Med 
Surg 2010, 12(8):584–591.
Consulting Editor  Mark P . Rondeau(continued)  Ileus

758  Blackwell’s Five-Minute Veterinary Consult  
IIllicit/Club Drug Toxicosis
  BASICS
OVERVIEW
Intoxication with illicit/club drugs includes 
various pharmaceuticals—barbiturates, 
benzodiazepines, cocaine, gamma hydroxy­
butyric acid (GHB), lysergic acid diethylamide 
(LSD), marijuana, methylenedioxymetham­
phetamine (MDMA: ecstasy), methampheta­
mine and other designer amphetamines, 
opioids, and phencyclidine (PCP).
• Barbiturates—sedative hypnotics causing 
CNS depression. • Cocaine—myocardial 
stimulant and increases catecholamine and 
serotonin levels, causing CNS stimulation. 
• GHB—synthetic γ­aminobutyric acid 
(GABA) derivative causing CNS depression. 
• LSD—CNS stimulation and hallucinations 
by increasing serotonin and glutamate in CNS, 
binds dopamine and α­adrenergic receptors. 
• MDMA—increases serotonin and catechola ­
mines in CNS, leading to CNS stimulation 
and hallucinations. • Opioids—bind to opioid 
receptors causing CNS depression. • PCP—
inhibits glutamate and stimulates α­adrenergic 
receptors; potentiates effects of norepineph ­
rine, epinephrine, and serotonin; sympathomi ­
metic and hallucinogen.
• Cardiovascular—cocaine, GHB, LSD, 
MDMA, PCP: arrhythmias, hypertension; 
barbiturates, opioids: arrhythmias, hypo­
tension. • Musculoskeletal—cocaine, PCP: 
tremors. • Nervous—cocaine, LSD, MDMA: 
stimulation; barbiturates, GHB: depression; 
opioids, PCP: sedative to stimulatory effects, 
ataxia. • Ophthalmic—cocaine, LSD, 
MDMA: mydriasis; opioids: miosis. 
• Respiratory—barbiturates, opioids: 
respiratory depression (rare).
SIGNS
• Barbiturates—sedation (rarely agitation), 
ataxia, bradycardia, hypotension, respiratory 
depression (rare), coma. • Cocaine—agitation, 
mydriasis, tachycardia, hypertension, tremors, 
seizures. • GHB, opioids—lethargy, weakness, 
coma, respiratory depression. • LSD—  
mydriasis, disorientation, hallucinations, 
agitation (rarely sedation), tachycardia.
• MDMA—agitation, mydriasis, hyper­
thermia, tachycardia, tremors, hallucinations, 
seizures. • PCP—depression to agitation, 
hypertension, tachycardia, tremors, seizures.
Ingestion of club drugs may occur in animals 
that live with people who take these pharma ­
ceuticals or in police dogs.  DIAGNOSIS
• Barbiturates, GHB, opioids—meningitis, 
hepatic encephalopathy, ethanol, ethylene 
glycol, phenothiazines. • Cocaine—ampheta­
mines, caffeine, metaldehyde, MDMA. 
• LSD, MDMA, PCP—meningitis, hepatic 
encephalopathy, amphetamines, cocaine, 
ketamine, psilocybin, serotoninergic 
medications (selective serotonin reuptake 
inhibitors, etc.).
No direct abnormalities. May see creatine 
kinase and K elevation (rhabdomyolysis) and 
myoglobinuria secondary to tremors.
Over ­the­counter illicit urine drug screens 
available; not approved for use in animals, but 
appear to be reliable except for marijuana 
(false negative). GC/MS can detect all, but 
turnaround time decreases usefulness.
  TREATMENT
• Inpatient care in dark quiet place; thermo­
regulation and fluid therapy to maintain body 
temperature and BP; fluids will also help to 
protect kidneys from myoglobinuria. • Monitor 
for respiratory depression (barbiturates, 
opioids); intubate and ventilate if needed. 
• Emesis (if asymptomatic and recent 
ingestion) or gastric lavage (if large amount 
• Activated charcoal (1–2 g/kg PO) with 
cathartic (if severe signs expected). 
• Agitation—phenothiazines (acepromazine 
0.025–0.05 mg/kg IV, titrate up as needed); 
cyproheptadine (dog: 1.1 mg/kg; cat: 2–4 mg 
PO q4–6h or can be given rectally if 
vomiting). • Agitation, seizures—benzodiaz­
epines (diazepam 0.5–2 mg/kg IV); see 
Contraindications. • T remors—methocarba­
mol (50–150 mg/kg IV). • Tachycardia—
propranolol (0.02 mg/kg IV). 
• Naloxone—reversal for opioids (0.01–
0.1 mg/kg IV).
Do not use diazepam with MDMA (increases 
dysphoria and morbidity).  FOLLOW-UP
BP , heart rate, urine color—q1h, then less 
frequently if patient remains stable.
Signs occur within minutes. Most will have a 
good prognosis if treated and recover in 
24–36 hours.
• Barbiturates, LSD, cocaine, and MDMA 
have been associated with severe birth defects. 
• Opioids and PCP have been associated with 
fetal intoxication and low birthweight.
SEE ALSO
SNRIs.
• Benzodiazepine and Other Sleep Aids 
• Marijuana Toxicosis.
• GHB = gamma hydroxybutyric acid.
• LSD = lysergic acid diethylamide.
• MDMA = methylenedioxymethampheta­
mine, ecstasy.
Klatt CA. Club drugs (MDMA, GHB, 
flunitrazepam, and bath salts). In: Hovda L, 
Brutlag A, Poppenga RH, Peterson K, eds., 
Blackwell’s Five ­Minute Veterinary Consult 
Toxicology, 2nd ed. Ames, IA: Wiley ­
Blackwell, 2011, pp. 245–252.

Canine and Feline, Seventh Edition  759
IImidazoline Toxicosis
  OVERVIEW
• Sympathomimetic drugs used for topical 
vasoconstrictive effects in ophthalmic 
anti-redness drops and nasal decongestant 
sprays.
• Oxymetazoline, naphazoline, tetrahydro -
zoline, brimonidine, and xylometazoline are 
imidazolines commonly used in prescription 
and over-the-counter ophthalmic and nasal 
products.
• Central and peripheral alpha2 adrenergic 
agonist activity. In overdose, central activity 
predominates, resulting in norepinephrine 
release and clinical signs of hypotension, 
bradycardia, and sedation.
• Companion animal pharmacokinetic 
data limited. Imidazolines considered to 
have narrow margin of safety, with no 
known therapeutic dose in veterinary 
medicine.
• Absorption rapid and nearly complete when 
ingested.
• Imidazolines partially metabolized in 
liver and eliminated mostly unchanged in 
urine.
• Cardiovascular—early transient tachy -
cardia and hypertension followed by 
prolonged bradycardia and hypotension, 
arrhythmias, pallor, slow capillary refill 
time.
• Nervous—sedation, lethargy, ataxia, 
weakness, tremors, rare seizures, rare 
paradoxical agitation, coma.
• Ophthalmic—miosis.
Dogs primarily; cats rarely.
SIGNS
• Lethargy and sedation.
• Early transient hypertension and 
tachycardia transitioning to prolonged 
bradycardia and hypotension.
• Pallor with prolonged capillary refill  
time.
• Ataxia.
• Miosis.
• T remors.
• Coma.
• Death.  DIAGNOSIS
• Other alpha agonist drugs—clonidine, 
tizanidine, medetomidine, dexmedetomidine, 
xylazine, amitraz.
• Marijuana, methanol, ethanol.
• Beta adrenergic blocker toxicosis—
metoprolol, atenolol, propranolol.
• Calcium channel blocker toxicosis—
diltiazem, amlodipine, verapamil.
• Primary cardiac disease with signs of 
Consider monitoring blood glucose and 
electrolytes in symptomatic patients.
N/A
• ECG monitoring—arrhythmias, 
bradycardia vs. tachycardia depending on 
stage of presentation.
• Blood pressure monitoring—early 
hypertension vs. later prolonged hypotension.
N/A
  TREATMENT
• Emergency care with any exposure—narrow 
margin of safety, signs develop at low doses.
• Decontamination—emesis induction is not 
recommended: rapid absorption and early 
onset of clinical signs; activated charcoal only 
in asymptomatic animals presenting early.
• IV fluid therapy to correct dehydration and 
hypotension; IV fluid diuresis not expected to 
enhance excretion; colloids if no response to 
crystalloid IV fluid therapy.
• Activated charcoal (1 g/kg PO) with 
cathartic × 1 dose in asymptomatic patients 
presenting early (<1–2 hours after ingestion); 
avoid use in symptomatic patients.
• Alpha2 adrenergic antagonists—atipamezole 
50 μg/kg IV/IM may be used to reverse severe 
sedation and bradycardia; give ¼ dose IV and 
remainder IM to avoid worsening hypotension; 
administer additional doses PRN based on 
clinical signs; alternatively, yohimbine 
0.1 mg/kg IV may be used.• Bradycardia—atropine 0.01–0.02 mg/kg 
IV PRN; avoid use if hypertensive.
• Hyperactivity—diazepam (0.5–1 mg/kg 
IV) or butorphanol (0.2–0.8 mg/kg IM/IV) 
PRN.
• Seizures—diazepam (0.5–1 mg/kg IV) 
PRN.
• T remors—diazepam (0.5–1 mg/kg IV) or 
methocarbamol (50–220 mg/kg IV slowly, up 
to a daily dose of 330 mg/kg)
• Vomiting—maropitant (1 mg/kg SC/IV 
q24h) PRN.
Naloxone 0.011–0.022 mg/kg IV/IM PRN 
may be tried if atipamezole and yohimbine 
are unavailable. Mechanism of action is 
unknown, and results may be variable.
  FOLLOW-UP
Monitor heart rate, blood pressure, ECG, and 
temperature closely.
Keep imidazoline medications secured out of 
reach to prevent dogs from chewing and 
ingesting them.
• Expected course—up to 24–36 hours 
depending on specific product ingested.
• Prognosis is good with appropriate 
treatment; successfully treated patients are 
expected to make a full recovery.
• Animals with decreased renal function may 
experience prolonged duration of signs.
• Neonates and geriatric pets may be more 
sensitive.
• Limited data available, but some imidazolines 
have been shown to pass into milk.
• Very high doses of oxymetazoline have 
resulted in fetal abnormalities in rats.
Waratuke KE. Imidazoline decongestants. In: 
Blackwell, 2016, pp. 333–338.

760  Blackwell’s Five-Minute Veterinary Consult  
IImmunodeficiency Disorders, Primary
  BASICS
Diminished ability to mount an effective 
immune response due to heritable defects in 
the immune system.
• Defects in the cell-mediated, humoral, 
complement, and phagocytic systems have all 
• Defects involving the humoral immune 
response—associated with a high suscepti -
bility to bacterial infection.
• Defects involving the cell-mediated 
immune response—associated with a high 
susceptibility to viral, fungal, and protozoal 
• Defects in the phagocytic or complement 
system—associated with disseminated 
• Hemic/lymphatic/immune—defect in a 
specific cell population in lymphoid tissue.
• Skin/exocrine/respiratory/gastrointestinal—
chronic or recurrent infections.
• Other organ systems—dissemination of 
infection, failure to thrive.
GENETICS
Typically breed specific with variable modes 
of inheritance.
Rare
Species
• X-linked severe combined 
immunodeficiency—basset hounds, Cardigan 
Welsh corgis.
• Severe combined immunodeficiency 
disease—Parson Russell terriers.
• Immunoglobulin (Ig) A deficiency—beagles, 
German shepherd dogs, and Chinese Shar-Peis.
• IgM deficiency—Doberman pinschers
• Thymic hypoplasia—dwarfed Weimaraners.
• Cyclic hematopoiesis—gray collies.
• Chediak-Higashi syndrome—Persian cats.
• Leukocyte adhesion deficiency—Irish 
setters.
• Complement deficiency—Brittanys.
• Bactericidal defect—Doberman pinschers.
• T ransient 
hypogammaglobulinemia—Samoyeds.
Primary immunodeficiency diseases typically 
expressed in the first year of life.
X-linked recessive severe combined immuno-
deficiency disease of basset hounds—males 
affected and females are carriers.SIGNS
Depends on the level at which the immune 
response is defective; ranges from chronic 
respiratory and gastrointestinal signs and skin 
infections to life-threatening conditions.
• High susceptibility to infection and failure 
to respond to appropriate conventional 
• Skin infection.
• Signs often appear when maternal antibody 
concentrations decline.
• Vaccine-induced disease by modified live 
virus preparation.
• Hallmark—failure to thrive.
• Clinical signs attributable to infections.
CAUSES
  DIAGNOSIS
Patients must be rigorously evaluated for 
underlying disease process that may cause 
secondary (acquired) immunodeficient state 
(e.g., hyperadrenocorticism, feline leukemia virus 
[FeLV], feline immunodeficiency virus [FIV]).
CBC may indicate deficiencies in specifically 
affected cell lines or show chronic 
• Serum protein electrophoresis— 
demonstrate gross deficiency in immuno-
globulin concentration.
• Serum immunoglobulin quantitation—
evaluate humoral immune system, identify 
selective immunoglobulin deficiency, support 
diagnosis of agammaglobulinemia.
• Lymphocyte transformation test—evaluate 
the cell-mediated immune system and 
identify animals with T-lymphocyte 
• Bactericidal assays—evaluate neutrophil 
function.
• Serum concentration of complement 
components—diagnose complement deficiency.
• Enumeration of lymphocyte subsets by 
immunofluorescence with monoclonal 
antibodies—identify deficiency of specific 
cell lines.
• Other more specific tests to evaluate 
immune function in veterinary species are 
available, but obtaining reliable results 
generally requires access to research 
laboratories that perform these tests.DIAGNOSTIC PROCEDURES
In some patients, bone marrow and lymph 
node biopsy aids in classifying the type of 
immune deficiency.
• Lesions vary depending on the specific defect; 
most are the result of recurrent or opportunistic 
infection involving the skin, ear canal, and 
respiratory and gastrointestinal systems.
• Septicemia common in animals with severe 
defects.
• T-lymphocyte defects—hypoplastic or 
dysplastic lesions of the thymus and 
T-lymphocyte-dependent areas of secondary 
lymphoid tissues.
• B-lymphocyte defects—hypoplastic or 
dysplastic lesions of the bone marrow or 
B-lymphocyte-dependent areas of secondary 
• Lymphoid hypoplasia or hyperplasia may 
be seen, depending on the overall defect and 
the occurrence of infection.
  TREATMENT
• Hospitalization may be necessary to control 
life-threatening infection.
• Outpatient management possible for some 
patients.
Supportive care appropriate to the nature of 
the infection.
ACTIVITY
Determined largely by the severity of the 
defect and the occurrence of infection.
DIET
• Dietary management may be required to 
ensure that the patient is maintained at an 
adequate level of nutrition.
• Potential sources of infectious agents such 
as raw meat diets must be avoided.
• Inform client that the condition is incurable.
• Discuss why the patient has high suscepti-
bility to infection.
• Discuss and advise as to the heritability of 
the disease.
• Discuss the possibility of littermates being 
affected.
• Avoid/limit exposure to animals with 
infections or kennel situations.
• Antibiotics to control infections; culture 
and sensitivity testing important in patients 
with chronic recurrent infections.

Canine and Feline, Seventh Edition  761
I• γ-globulin or plasma preparations can be 
used in conjunction with antibiotics to control 
infection in patients with humoral defect.
• Symptomatic treatment for secondary diseases.
γ-globulin or plasma preparations should not 
be administered to patients with selective IgA 
deficiency because many affected patients 
have high concentrations of anti-IgA 
antibodies and may develop anaphylaxis.
Modified live virus vaccines should not be 
administered to patients with suspected 
T-lymphocyte deficiencies because they may 
induce disease in these patients.
  FOLLOW-UP
• For clinical signs of secondary infection.
• Routine physical examination to assess 
efficacy of antibiotic therapy.PREVENTION/AVOIDANCE
• Pedigree analysis to determine the mode of 
inheritance and prevent propagating the defect.
Infection
• The severity of the defect determines the 
course and prognosis.
• Patients with minor defects can be 
successfully managed.
SEE ALSO
Anaphylaxis Suggested Reading
Datz CA. Noninfectious causes of 
immunosuppression in dogs and cats. Vet 
40(3):459–467.
Felsburg PJ. Overview of the immune system 
and immunodeficiency diseases. Vet Clin 
North Am Small Anim Pract 1994, 
24(4):629–653.
Gershwin LJ. Autoimmune diseases in small 
Pract 2010, 40(3):439–457.
Consulting Editor  Melinda S. Camus(continued)  Immunodeficiency Disorders, Primary

762  Blackwell’s Five-Minute Veterinary Consult  
IImmunoproliferative Enteropathy of Basenjis
  BASICS
OVERVIEW
• Immune-mediated disease characterized by 
progressive, chronic intermittent diarrhea, 
anorexia, and weight loss, associated with 
intense lymphoplasmacytic, infiltrative 
gastroenteritis or enteritis and concurrent 
evidence of protein-losing enteropathy, 
malabsorption, and maldigestion. 
• Hypergammaglobulinemia present due to 
increased concentrations of serum immuno-
globulin (Ig) A. • Systems affected include 
gastrointestinal, immune, skin, renal, 
endocrine.
• Young to middle-aged Basenji—usually  
<3 years of age. • No sex predilection. 
• Related dogs often affected.
SIGNS
• Chronic intermittent diarrhea. • Severe 
progressive weight loss. • Anorexia often 
preceding diarrhea. • Variable vomiting.
• Attitude—usually bright and alert. 
• Bilaterally symmetric alopecia, ulceration of 
pinna. • Decreased body condition score. 
• Ascites, peripheral edema with severe 
disease.
• Pathogenesis unclear, but interaction 
between abnormal immune regulation, 
genetic predisposition, and possibly 
contribution by environmental factors is 
hypothesized. • Mode of inheritance not 
known, but autosomal recessive is suspected. 
• Stressful events may exacerbate clinical 
signs.
  DIAGNOSIS
• Lymphangiectasia. • Lymphoplasmacytic 
enteritis. • Intestinal lymphoma. 
• Eosinophilic enteritis. • Antibiotic-
responsive diarrhea. • Diet-responsive 
enteropathy. • Histoplasmosis. • Intestinal 
parasitism. • Giardiasis. • Exocrine 
 pancreatic insufficiency. • Hypoadreno -
corticism. • Hepatobiliary disease.
• Severe hypoalbuminemia. 
• Hyperglobulinemia. • Decreased albumin : 
globulin ratio. • Mature neutrophilia—more 
severe with advanced disease. • Mild, 
nonregenerative anemia of chronic disease. 
• Moderately increased hepatic enzymes 
(alanine transaminase [ALT] and aspartate transaminase [AST]) due to reactive 
• Hypergammaglobulinemia due to increased 
serum IgA. • May have hypergastrinemia and 
hyperchlorhydria. • May see changes in 
serum folate or hypocobalaminemia. • No 
one test or histologic finding definitive or 
pathognomonic.
IMAGING
generalized small bowel thickening (4–6 mm) 
with abnormal gastrointestinal wall layering 
and a lack of other visceral abnormalities.
• Endoscopic appearance of small bowel 
usually abnormal, but may be normal; 
biopsies always required for accurate 
diagnosis. • Genetic testing (DNA) not 
available at this time.
• Consistent pathologic lesions include 
uniform thickening of small bowel, 
generalized lymphoplasmacytic infiltration of 
intestinal lamina propria, lacteal dilation, 
crypt abscesses, and blunting and fusion of 
villous tips. • May be gastric rugal fold 
hypertrophy, lymphocytic gastritis, oxyntic 
gland hyperplasia, and/or gastric mucosal 
atrophy. • Presence and severity of gastric 
lesions do not correlate with severity of 
intestinal lesions. • Other associated lesions 
include thyroid parafollicular cell atrophy, 
ulceration of pinna, gastric acinar atrophy, 
and glomerulonephritis.
  TREATMENT
• Outpatient medical management unless 
dehydration or other severe complications 
exist. • Advise clients not to breed affected 
dogs or their littermates. • Minimize stressful 
episodes. • Use dietary trials (ideally fat- 
restricted, highly digestible diets) to 
determine what diet is best tolerated.
Immunosuppressive/Anti-inflammatory 
Drugs
• Variable success reported, but considered 
mainstay of treatment. • Prednisone—2 mg/kg 
PO q24h for 2–4 weeks, then slowly taper 
over 3–4 months to achieve 0.5–1 mg/kg PO 
q48h or lowest effective dose. 
• Chlorambucil—0.25 mg/kg PO q72h with 
monitoring for adverse effects, or other 
immunosuppressive medications can be tried.Antibiotics
• T rials of antibiotics are variably helpful for 
affected individuals that may have antibiotic-
responsive diarrhea. 
• Metronidazole—10 mg/kg PO q12h. 
• Tylosin—10–20 mg/kg PO q12h.
Nutritional Supplements/Adjunctive 
Treatment
Use of probiotics is commonly advised and 
may favor reduced risk of dysbiosis and 
lowered state of inflammatory responses by 
gut-associated lymphoid tissues, but no 
specific data available to support this 
hypothesis.
Anticholinergics contraindicated.
  FOLLOW-UP
• Diarrhea and weight loss usually show 
initial improvement with treatment, but 
recurrence of signs is common. • Long-term 
prognosis is poor over course of months to a 
few years.
MacLachlan NJ, Breitschwerdt EB, Chambers 
JM, et al. Gastroenteritis of Basenji dogs. 
Vet Pathol 1988, 25(1):36–41.
Spohr A, Koch J, Jensen AL. 
Ultrasonographic findings in a Basenji with 
immunoproliferative enteropathy. J Small 
Anim Pract 1995, 36:79–82.
Author  Megan McClosky

Canine and Feline, Seventh Edition  763
IIncontinence, Fecal
  BASICS
Inability to retain feces or generate a 
coordinated and appropriate act of 
• The colon, rectum, and anus are primary 
sites of function in normal defecation. 
• Coordinated contractions of the circular and 
longitudinal smooth muscle of the colon result 
in orderly accumulation of fecal matter, which 
is stored in the descending colon. • Intense 
propulsive activity down the length of the 
colon, called mass movement, is stimulated by 
the autonomic nervous system and moves fecal 
matter toward the anus. • The internal anal 
sphincter is composed of smooth muscles while 
the external anal sphincter is composed of 
striated muscle; parasympathetic innervation to 
the internal sphincter is provided by the pelvic 
nerves via the sacral segments (S1–S3); 
sympathetic innervation is provided by the 
hypogastric nerves via the lumbar segments 
(L1–L4); parasympathetic stimulation leads to 
relaxation of the internal sphincter and 
contraction of the rectum, whereas sympathetic 
stimulation leads to contraction of the internal 
sphincter and relaxation of the rectum; the 
striated muscles of the external anal sphincter 
are under conscious control via the caudal rectal 
nerve (a branch of the pudendal nerve). 
• Neurogenic sphincter incompetence can be 
caused by damage or denervation of the 
pudendal nerve, lesions that cause lumbar or 
sacral spinal segment dysfunction, autonomic 
dysfunction, or generalized peripheral neuropa -
thy or myopathy. • Non-neurogenic sphincter 
incompetence is caused by damage to the anal 
sphincters. • Damage to, or degeneration of, 
the levator ani and coccygeus muscles may also 
contribute to fecal incontinence. • Reservoir 
fecal incontinence develops when disease 
processes reduce the capacity or compliance 
of the rectum; the patient is aware of the need 
to defecate, but sphincter control is over -
whelmed by fecal volume or spastic colorectal/
anal disease.
GENETICS
N/A
Unknown
N/A
Species
N/A
Increased incidence in older patients.
N/A
SIGNS
• Reservoir incontinence—urge to defecate; 
frequent, conscious defecation; defecation may 
be associated with tenesmus or dyschezia. 
• Sphincter incontinence—involuntary 
expulsion or dribbling of fecal material, 
especially during excitement or barking and 
coughing. • History of neurologic signs, 
anorectal surgery, and/or trauma. • Concurrent 
urinary incontinence suggests neurogenic 
sphincter incontinence.
• Reservoir incontinence—anorectal sensitivity 
or pain on digital palpation, rectal mass or 
thickening of rectal mucosa; external anal 
sphincter tone and perineal reflex are normal. 
• Non-neurogenic sphincter incontinence—
evidence of perineal trauma or perianal fistulae; 
anal reflex is present, but external anal 
sphincter may not be completely closed if 
sphincter has been anatomically disrupted. 
• Neurogenic sphincter incontinence—loss of 
tone to external anal sphincter; perineal reflex 
is absent or diminished. • Neurologic 
examination findings may include lumbosacral 
pain, paraparesis, paraplegia, decreased 
postural reactions, hopping, paw placements, 
normal to decreased reflexes (patellar, 
withdrawal, perineal reflex), or absent 
nociception in perineum or tail. • Diffuse 
lower motor neuron (LMN) signs suggest 
generalized peripheral neuropathy or 
myopathy; these are rare causes of fecal 
incontinence in small animals.
CAUSES
Reservoir Incontinence
• Colorectal disease—colitis, irritable bowel 
syndrome, and neoplasia. • Diarrhea—large 
volumes of feces from any cause can overwhelm 
the absorptive and storage capacity of the colon.
Non-neurogenic Sphincter Incontinence
• T raumatic anal injuries. • Neoplasia. 
• Iatrogenic—complication of anorectal 
surgery. • Anorectal or perianal diseases—e.g., 
perianal fistulae. • Mucocutaneous diseases—
e.g., immune-mediated, infectious.
Neurogenic Sphincter Incontinence
• Iatrogenic—traumatic nerve injury as 
postoperative complication. • Diseases affecting 
dorsal funiculus (L4 and cranial). • Spinal 
cord—arachnoid diverticulum, arachnoid cysts, 
spinal malformations, syringomyelia, trauma, 
intervertebral disc disease, neoplasia, infectious 
or inflammatory meningomyelitis, fibrocarti -
laginous embolism, myelomalacia. • Degenerative lumbosacral stenosis—L6–L7 or 
L7–S1, intervertebral disc disease, severe 
spondylosis deformans, synovial cysts, 
ligamentous hypertrophy, lumbosacral 
instability, neoplasia. • Peripheral neuropathy—
infectious, endocrine/metabolic, immune-
mediated, drug-induced (e.g., vincristine), 
dysautonomia, idiopathic. • Diffuse 
neuromuscular diseases—neuropathies, 
junctionopathies, myopathies (LMN unit). 
• Degeneration (aging)—multiple factors likely 
involved, including atrophy of muscles involved 
in fecal continence, weakness, degenerative 
neuropathy, cognitive dysfunction.
• Colonic disease. • Anorectal disease and 
surgery. • Neurologic disease.
  DIAGNOSIS
• Primary GI disease can increase urge to 
defecate; these animals typically attempt to go 
outside to defecate, or posture to defecate. 
• Behavioral disorders (e.g., separation anxiety) 
often associated with destructive activities or 
excessive vocalization. • Inadequate house 
training usually occurs in young dogs or dogs 
recently introduced to indoor environment or 
in cats with litter box aversion.
• Thyroid testing. • If junctionopathy suspected, 
consider submitting acetylcholine receptor 
antibody titers. • If polymyositis suspected, submit 
Toxoplasma  and Neospora  titers. • Rectal scraping 
for cytology is indicated in regions where 
Heterobilharzia , histoplasmosis, or pythiosis is 
endemic; rectal cytology may also indicate presence 
of neoplasia. • Zinc sulfate flotation tests and fecal 
PCR, ELISA, or culture to detect Giardia  sp., 
bacterial, viral, and protozoal infections. • Serum 
trypsin-like immunoreactivity to rule out 
exocrine pancreatic insufficiency. • Serum 
cobalamin and folate concentrations to 
IMAGING
• Lateral and ventrodorsal survey radiography 
of lumbosacral spine may show evidence of 
intervertebral disc extrusion, spondylosis 
deformans, discospondylitis, vertebral 
neoplasia, lumbosacral trauma, or vertebral 
malformations. • Abdominal ultrasound, 
barium radiographic studies, and CT may 
help identify masses or intestinal lining 
abnormalities. • MRI is optimum diagnostic 
tool to demonstrate specific spinal cord and 
brain lesions. • CT with IV contrast or CT 
with myelography may also demonstrate 
compressive lesions within spinal canal.

764  Blackwell’s Five-Minute Veterinary Consult  
IDIAGNOSTIC PROCEDURES
• Full-thickness or endoscopic GI biopsies if 
diarrhea present. • Colonoscopy and colorectal 
mucosal biopsy if reservoir incontinence 
suspected. • Electromyography/nerve 
conduction studies. • Muscle and nerve biopsy 
for myopathy and peripheral neuropathy. 
• Analysis of cerebrospinal fluid (CSF) may 
reveal evidence of CNS infectious or 
inflammatory process, neoplasia, or trauma.
  TREATMENT
Inpatient vs. outpatient depends on underlying 
disease.
• In recumbent patients or patients with 
difficulty ambulating and fecal incontinence, 
nursing care is of paramount importance. • To  
prevent decubital ulcers, rotate recumbency 
every 2–4 hours and utilize a water bed. 
• Soiled bed should be changed immediately, 
and soiled hair coat and skin should be washed 
with gentle soap and warm water and dried 
thoroughly. • Occasional warm water enemas 
will diminish volume of feces in colon and 
may decrease incidence of inappropriate 
defecation. • Reflex defecation may be 
stimulated by applying warm washcloth to 
anus or perineum. • Physical therapy options 
include massage, passive range of motion 
exercises, and assisted walking; hydrotherapy, 
thermal therapies, and acupuncture may be 
considered when appropriate.
ACTIVITY
Animal should be encouraged to go outside 
to urinate and defecate every 4–6 hours. Sling 
walking may be necessary.
DIET
Fecal volume can be reduced by feeding 
low-residue commercial diets or foods such as 
cottage cheese and rice. Feed pet at established 
times to better control times needed to defecate.
• Prognosis for recovery of function is poor if 
successfully corrected; discuss prognosis with 
client early in evaluation to avoid unrealistic 
expectations. • Environmental changes (e.g., 
providing designated area that is easy to clean) 
may increase client satisfaction and thus avoid 
euthanasia of otherwise healthy animal.
Fascial slings, silicone elastomer slings, and 
other surgical techniques to repair external 
anal sphincter or improve anorectal angulation 
have been attempted with low success rates.  MEDICATIONS
• Diphenoxylate (0.1–0.2 mg/kg PO q12h) 
and loperamide (0.1–0.2 mg/kg PO q8–12h) 
are opiate motility-modifying drugs; they 
inhibit GI motility, thus increasing the 
amount of water absorbed from the feces. 
• Anti-inflammatory agents, such as 
glucocorticoids, metronidazole, and 
sulfasalazine (dogs only), may benefit patients 
with suspected reservoir incontinence due to 
inflammatory bowel disease or colitis. 
• Improvement in signs may be achieved if 
specific therapy for perianal fistulae, colitis, or 
other reservoir or non-neurogenic causes of 
incontinence can be given, but there are no 
specific drugs effective in patients with 
neurogenic incontinence.
• Do not use motility-modifying drugs in 
patients if infectious or toxigenic cause of 
diarrhea is suspected. • Do not use opiate 
motility modifiers in debilitated patients, or 
patients with impaired liver or renal function. 
• Do not use diets containing high concentra -
tions of insoluble fibers as this will produce 
large, bulky stool that is difficult to pass or 
may cause obstipation.
• Opiate motility-modifying drugs may cause 
sedation. • Use loperamide with caution in 
patients with p-glycoprotein defects.
Increased sedation and respiratory depression 
are possible when opiates are used concurrently 
with other CNS depressants (e.g., barbiturates, 
tranquilizers).
N/A
  FOLLOW-UP
• If fecal incontinence is due to underlying 
neurologic cause, use serial neurologic 
examinations to monitor patient progress. 
• Radiographic procedures, electromyography, 
CSF analysis, and MRI can also be used to 
follow progress. • Check fecal consistency and 
volume and make sure pet does not become 
constipated or obstipated. • Examine perianal 
skin and hair coat to ensure there is no fecal 
matter and secondary inflammation or 
infection. • Adjust diet to find appropriate 
therapy for each individual patient.
Neurogenic sphincter incontinence is often 
unresponsive despite appropriate dietary, 
medical, and surgical treatment.
50% of pets with fecal incontinence were 
euthanized in a recent study.
N/A
N/A
• Exposure to animal feces increases risk of 
exposure to zoonotic parasites. • Advise 
clients about zoonotic diseases (e.g., 
salmonellosis, cutaneous and visceral larval 
migrans, and toxoplasmosis).
N/A
SYNONYMS
N/A
• LMN = lower motor neuron.
de Lahunta A, Glass E, Kent M. Lower motor 
neuron: spinal nerve general somatic 
efferent system. In: de Lahunta A, Glass E, 
Kent M, Veterinary Neuroanatomy and 
Clinical Neurology, 4th ed. St. Louis, MO: 
Elsevier Saunders, 2015, pp. 102–161.
Foley P . Constipation, tenesmus, dyschezia, and 
fecal incontinence. In: Ettinger SJ, Feldman 
Elsevier Saunders, 2017, pp. 171–174.
Schermerhorn T. Gastrointestinal 
endocrinology. In: Ettinger SJ, Feldman 
Elsevier Saunders, 2017, pp. 1833–1838.
Washabau RJ. Dysmotility/fecal incontinence. 
In: Washabau RJ, Day MJ, eds., Canine and 
Elsevier Saunders, 2013, pp. 791–798.
Debra L. Zoran.
available onlineIncontinence, Fecal  (continued)

Canine and Feline, Seventh Edition  765
I
Incontinence, Urinary
  BASICS
Loss of voluntary control of micturition, 
usually observed as involuntary urine leakage.
Most commonly a disorder of the storage 
phase of micturition, resulting from impaired 
urethral sphincter mechanism, detrusor 
hyperreflexia, or poor bladder compliance. 
Congenital malformations such as ectopic 
ureters or urethral malformation can also 
cause incontinence. Overflow incontinence 
can result from partial or complete functional 
urethral obstruction or bladder atony.
• Renal/urogenital.
• Nervous.
• Skin—urine scald, perineal and ventral 
Urinary incontinence may affect up to 20% 
of female spayed dogs and up to 30% of those 
weighing over 20 kg.
• Dog and rarely cat.
• Most common in spayed female dogs.
• More common in dogs >20 kg.
• Overflow incontinence most common in 
young to middle-aged, large- to giant-breed 
male dogs.
CAUSES
Anatomic
• Congenital abnormality of the urethral 
sphincter mechanism.
• Ectopic ureters that terminate in the 
bladder neck, urethra, vestibule, or vagina.
• Shortened (hypoplastic) urethra.
• Ureterovaginal hypoplasia/aplasia (cats).
• Cystic hypoplasia.
• Patent urachal remnant.
• Intrapelvic bladder interfering with abdominal 
pressure transmission to the proximal urethra.
• Vestibular or vulvar conformational 
abnormalities contributing to urine pooling 
and leakage.
• Central or peripheral lower motor neuron 
injury to the sacral spinal cord and pudendal 
nerve leading to weak urethral closure and 
flaccid bladder.
• Overflow incontinence secondary to upper 
motor injury of the thoracolumbar spinal 
cord and loss of inhibitory signaling to the 
urethral sphincter.
• Dysautonomia leading to urine retention 
and overflow incontinence.
• Damage to local reflex arc allowing for 
relaxation of the urethral sphincter when the 
detrusor contracts.• Lesions of the cerebellum or cerebral 
micturition center affecting inhibition and 
voluntary control of voiding, resulting in 
frequent involuntary urination or leakage of 
small amounts of urine.
• Feline leukemia virus–associated myelopathy 
leading to progressive paresis or paralysis.
Urinary Bladder Dysfunction
• Bladder atony leading to incomplete 
voiding and overflow incontinence.
• Bladder overdistension with loss of cellular 
tight junctions and incomplete contractile 
signal transmission.
• Bladder fibrosis leading to poor compliance 
and decreased storage capacity.
• Detrusor hyperreflexia (overactive bladder) 
and poor compliance.
Urethral Disorders
• Congenital or acquired urethral sphincter 
mechanism incompetence (most common).
• Functional outlet obstruction leading to 
overflow incontinence (detrusor urethral 
dyssynergia).
• Mechanical outflow obstruction from 
enlarged prostate, benign or malignant 
neoplasia, urolith, foreign body, or external 
Urine Retention
Overflow incontinence when intravesicular 
pressure exceeds outlet resistance.
Mixed Urinary Incontinence
Any combination of factors in dogs and cats 
leading to involuntary urine loss. Not 
typically defined in the way human mixed 
urinary incontinence is (overactive bladder 
and stress incontinence).
• Large-breed (>20 kg) spayed female dog.
• Early spay (<12 weeks).
• Breed predispositions are possible.
• Intrapelvic bladder.
• Urogenital conformational abnormalities 
affecting bladder neck, urethral length, or 
vestibule.
• Other possible risk factors include obesity, 
tail-docking, and polyuria.
  DIAGNOSIS
• Voluntary inappropriate urination.
• Prostatic or vaginal discharge.
• Polyuria—may worsen minor incontinence 
because of increased pressure on already 
weakened urethral sphincter mechanism.
• Hematology and serum biochemistry are 
indicated in patients with polyuria and 
polydipsia.• CBC and serum biochemistry are usually 
normal unless comorbidities exist.
• Urinalysis frequently normal.
• Urine sediment may indicate urinary tract 
infection or polyuria.
• Urine culture may be indicated if clinical 
signs (straining to urinate, pollakiuria) and 
urine sediment (pyuria, bacteriuria, hematuria) 
are consistent with urinary tract infection.
• Cats should be tested for feline leukemia virus.
• Additional testing for causes of polyuria 
and polydipsia may be indicated based on 
serum biochemistry and urinalysis results.
IMAGING
• Plain radiography may identify a pelvically 
placed bladder.
• Intravenous contrast excretory urography 
may identify dilated or ectopic ureters; 
however, careful attention must be paid to 
proper technique and the sensitivity of the 
imaging is inferior to other methods.
• Retrograde contrast vaginourethrography 
may reveal congenital abnormalities of the 
vagina, urethra, and vestibule, and 
occasionally ectopic ureters.
• Single- or double-contrast cystourethrography 
allows for accurate assessment of bladder 
position and urethral length.
• Imaging of the dog or cat with acquired 
urethral sphincter mechanism incompetence, 
the most common cause of acquired urinary 
incontinence, is usually normal.
• Ultrasound assessment may detect ureteral 
dilation or ectopic ureters; however, the 
sensitivity is very operator dependent.
• Allows for evaluation of kidneys, bladder, 
and prostate.
CT Findings
CT excretory urography is currently the 
imaging modality of choice to diagnose 
ectopic ureters.
• Neurologic examination—tail tone, anal 
tone, perineal reflexes and sensation, and 
bulbospongiosus reflexes.
• Orthopedic examination—determination 
of pain or difficulty posturing to urinate, 
which can lead to urine retention.
• Urethral catheterization—to determine 
patency of urethra and residual urine volume 
in patients with suspected urine retention and 
overflow incontinence.
• Cystoscopy—evaluates urethra and bladder 
as well as visualization of position and shape 
of ureteral openings.
• Urodynamic assessment—may document 
decreased urethral pressure or detrusor 
hyperreflexia; limited availability at some 
specialty clinics.

766  Blackwell’s Five-Minute Veterinary Consult  
I  TREATMENT
• Usually outpatient.
• Medical therapy is primary treatment for 
patients with urethral sphincter mechanism 
• Urinary tract infection should be treated 
appropriately if identified.
• Address partial urethral obstructive and 
neurologic disorders if identified.
• Ectopic ureters should be corrected either 
by cystoscopic laser ablation if intramural 
(common) or surgery if extramural (rare).
• Anatomic disorders should be identified 
and corrected if possible.
• Functional abnormalities of the bladder or 
urethra may require medical treatment.
• Bulking agents such as bovine cross-linked 
collagen may be injected into urethral 
submucosa, or surgical salvage procedures 
such as placement of urethral hydraulic 
occluder if urethral sphincter incompetence 
not responsive to medical therapy.
Urethral Sphincter Mechanism 
Incompetence
• Alpha-adrenergic agonist treatment (e.g., 
phenylpropanolamine 1–2 mg/kg PO q8–12h) 
or estrogen compounds (e.g., estriol 2 mg/dog 
PO q24h for 2 weeks, then decrease dose q2 
weeks to lowest effective dose; diethylstilbestrol 
0.1–1 mg/dog PO q24h for 5–7 days, then 
0.1–1 mg/dog q5–7 days PRN).
• Phenylpropanolamine and estrogens may 
be used in combination in spayed females and 
may have a synergistic effect.
• Imipramine (5–15 mg/dog PO q12h), a 
tricyclic antidepressant with cholinergic and 
alpha-agonist effects, may be of use if other 
medical therapy fails, especially if detrusor 
hyperreflexia is suspected as well.
• Testosterone cypionate (2.2 mg/kg IM q30–45 
days) may be used in males with urethral 
sphincter mechanism incompetence; however, its 
efficacy is far below phenylpropanolamine.Detrusor Hyperreflexia
Antimuscarinic agents (oxybutynin chloride 
0.2–0.3 mg/kg PO q8–12h or 1.25–5 mg/
dog PO q8–12h; imipramine 5–15 mg/dog 
PO q12h).
Functional Outflow Obstruction
See Urinary T ract Obstruction.
• Do not use estrogens in males or intact 
females.
• Do not use alpha agonists in patients with 
hypertension, and use with caution in 
patients with conditions that predispose to 
• Do not use anticholinergics in patients with 
glaucoma or cardiac disease.
• Adrenergic agonists can cause hypertension, 
changes in appetite, and restlessness.
• Adverse effects of estrogen use include vulvar 
swelling, mammary development, and 
attractiveness to males; these are usually dose 
dependent and will subside with dose 
reduction; always use the lowest effective dose.
• Bone marrow suppression is extremely rare 
secondary to estrogen use at the 
recommended doses.
• Testosterone use can lead to signs of 
aggression and increased libido in males.
• Anticholinergic agents can cause nausea, 
vomiting, and constipation.
• Do not administer tricyclic antidepressants 
concurrently with monoamine oxidase 
inhibitors (e.g., amitriptyline, clomipramine, 
imipramine).
• Hypertensive risk increases with concurrent 
use of alpha agonists and tricyclic 
  FOLLOW-UP
• Monitor blood pressure periodically in 
patients receiving alpha agonists.
• Monitor vulvar and mammary swelling in 
patients receiving estrogen treatment.
• Monitor prostate size in males receiving 
testosterone.
• Once continence is achieved, gradually 
reduce to lowest effective dose.• Perform urine cultures to guide treatment 
and prevent resistance of symptomatic 
urinary tract infections.
• Recurrent and resistant urinary tract 
• Urine scald and perineal (females) or 
ventral abdominal (males) dermatitis.
• Refractory incontinence.
• Hydroureter and hydronephrosis in some 
ectopic ureter patients, even after correction.
Dogs with congenital anomalies such as 
ectopic ureters should be removed from the 
breeding population.
SYNONYMS
• Hormone-responsive incontinence.
• Enuresis.
SEE ALSO
Acierno M, Labato M. Canine incontinence. 
Vet Clin North Am Small Anim Pract 2019, 
49(2):125–140.
Byron J, Taylor K, Phillips G, Stahl M. 
Urethral sphincter mechanism incompe-
tence in 163 neutered female dogs: 
diagnosis, treatment, and relationship of 
weight and age at neuter to development of 
disease. J Vet Intern Med 2017, 
31(2):442–448.
Author  Julie K. Byron
Jo R. Smith.
available onlineIncontinence, Urinary  (continued)

Canine and Feline, Seventh Edition  767
I
Infertility, Female—Dogs
  BASICS
Abnormal cycling, copulation failure, 
conception failure, or pregnancy loss in 
bitches.
• Normal fertility—requires normal estrous 
cyclicity with ovulation of normal ova into a 
patent, healthy reproductive tract; fertilization 
by normal spermatozoa; implantation of the 
conceptus into the endometrium; formation 
of the normal placenta; and maintenance of 
pregnancy in the presence of high progesterone 
concentration throughout the approximately 
2-month gestation.
• Breakdown in any of these processes causes 
infertility.
• Animals of all ages; more common in old 
animals.
• Dogs >6 years old—more likely to have 
underlying cystic endometrial hyperplasia; 
may be predisposed to uterine infection and 
failure of conception or implantation.
• Breeds predisposed to hypothyroidism—
may have higher prevalence; include golden 
retrievers, Doberman pinschers, dachshunds, 
Irish setters, miniature schnauzers, Great 
Danes, poodles, and boxers.
SIGNS
• Failure to cycle.
• Failure to cycle normally—shortened 
interestrous interval (interval of 4 months or 
less).
• Failure to copulate, poor semen quality, or 
lack of functional spermatozoa in the male.
• Failure to become pregnant and/or 
maintain pregnancy after normal copulation.
• Persistent estrus ( >3 weeks).
• Negative pregnancy exam after mating.
• Positive pregnancy with no subsequent 
parturition.
CAUSES
• Insemination at the improper time in the 
estrous cycle—most common.
• Subclinical uterine infection.
• Cystic endometrial hyperplasia.
• Male infertility factors.
• Hypercortisolism.
• Anatomic abnormality.
• Chromosomal abnormality.
• Abnormal ovarian function.
• Previous ovariectomy, hysterectomy, or 
ovariohysterectomy.• Brucella cani s infection.
• Silent estrus.
• B. canis .
• Hypercortisolism—endogenous or 
exogenous.
• Systemic viral infection—canine herpesvirus.
• Any chronic, debilitating disease.
• Congenital vaginal anomaly.
• Old age.
  DIAGNOSIS
Historical Information
• Extremely useful in distinguishing causes.
• Is the patient cycling?
◦ Primary anestrus = no overt estrous cycle 
by 2 years of age.
◦ Secondary anestrus = no overt estrous 
cycle within 1 year of a normal cycle.
• Has the patient conceived or given birth in 
the past? If so, how recently? Litter size? 
Percentage of stillbirths? Percentage of litter 
weaned?
• Is the patient free of systemic viral or 
protozoal infection?
• Is the patient capable of normal copulation?
• Was the patient bred to a male of proven 
fertility (i.e., litter whelped within previous 6 
months) at the proper time of the estrous 
cycle?
• Did the patient ovulate during the estrous 
cycle and maintain progesterone concen -
tration consistent with pregnancy during the 
entire gestation?
• Is the bitch euthyroid?
Serologic Test for  B. canis (Dogs)
• Rapid slide agglutination test—used as a 
screen; sensitive but not specific.
• If positive results—recommend recheck by 
an agar gel immunodiffusion test, bacterial 
culture, or PCR of whole blood or lymph 
node aspirate.
Serum Progesterone Measurement
• Should remain high throughout gestation.
• If concentration <2 ng/mL in mid-gestation 
and pregnancy loss occurs, insufficient luteal 
function indicated (hypoluteodism); see 
Abortion, Spontaneous (Early Pregnancy 
Loss)—Dogs, and Premature Labor.
• Concentration >2 ng/mL—may indicate 
diestrus, silent heat (estrus with no overt 
behavioral or physical changes), or pathologic 
production of progesterone from a luteal 
ovarian structure, functional ovarian 
neoplasm, or the adrenal gland.• Quantitative (chemiluminescence, 
fluorescence, enzyme immunoassay) 
progesterone assay is important to detect 
levels <2.0 ng/mL; rapid in-hospital assays are 
least accurate between 2 and 5 ng/mL.
• Progesterone may be measured during 
proestrus and estrus to predict ovulation time 
and optimize breeding management.
• Concentration and ovulation:
◦ 1–1.9 ng/mL, probable ovulation in 3 
days (recheck).
◦ 2–2.9 ng/mL, ovulation in 2 days.
◦ 3–3.9 ng/mL, ovulation in 1 day.
◦ 4–10 ng/mL, ovulation that day.
• Optimal breeding day for single breeding to 
produce maximum litter size—2 days after 
• Day of ovulation from onset of proestrus or 
estrus extremely variable; not well correlated 
with standing behavior (see Breeding, 
Timing).
Other Tests
• Bacterial culture for uterine organisms—
vaginal discharge originating in the uterus 
during proestrus or estrus is collected directly 
by hysterotomy or transcervical catheteriza-
tion, or indirectly from the anterior vagina 
using a guarded swab.
• Thyroid hormone testing—resting serum 
concentration of T3 or T4 and thyroid 
stimulating hormone (TSH).
• Serologic testing—canine herpesvirus; see 
Loss)—Dogs.
• Karyotype—performed on patients with 
primary or persistent anestrus; can identify 
chromosomal abnormalities that can cause 
abnormal sexual differentiation.
• Serum cortisol concentration—if the resting 
serum cortisol is high, the underlying cause 
should be identified; see Hyperadrenocorticism 
(Cushing’s Syndrome)—Dogs.
• Semen evaluation—direct evaluation to rule 
out oligospermia or azoospermia; alternatively, 
may test-breed the male to another female to 
prove fertility; rule out azoospermia in tomcat 
by finding spermatozoa in a vaginal flush or 
swab specimens from the queen or in urine 
collected by cystocentesis from the tom; see 
Infertility, Male—Dogs.
• Serum anti-Müllerian hormone/
progesterone, luteinizing hormone (LH)/
estrogen for determination of ovarian 
presence; see Ovarian Remnant Syndrome.
IMAGING
• Radiography—normal ovaries and a 
nongravid uterus usually not visible with 
radiography; large ovaries may indicate cystic 
ovarian disease or neoplasia; visible uterus 
may indicate cystic endometrial hyperplasia.
• Ultrasound—may diagnose pregnancy as 
early as 20–24 days after ovulation; useful for 
documenting pregnancy loss; useful for 
detecting suspected cystic ovarian or neoplastic 
ovarian disease, cystic endometrial hyperplasia,

768  Blackwell’s Five-Minute Veterinary Consult  
Iand intraluminal fluid; may be difficult to 
image normal ovaries and nongravid uterus—
operator dependent.
• Positive-contrast procedures—vaginography; 
hysterography; performed prepuberally or 
when the patient is in estrus; may reveal 
anatomic abnormality (e.g., abnormal 
structure and impatency); see Vaginal 
Malformations and Acquired Lesions.
• Laparotomy—assess anatomy of the tubular 
tract and gonads.
• Hysterotomy—to obtain a direct uterine 
culture specimen; biopsy of the uterus or 
ovaries.
  TREATMENT
• Heritable cause (e.g., thyroid insufficiency)—
counsel owner regarding removing the patient 
from the breeding program.
• Surgical resection of vaginal anomalies—
may ease natural service and vaginal delivery 
of pups.
• Surgical repair of impatent tubular 
tract—difficult procedure; prognosis for 
future fertility guarded.
• Surgical drainage of ovarian cysts—efficacy 
unknown.
• Unilateral ovariectomy of neoplastic 
ovary—future fertility depends on 
resumption of normal function of the 
remaining ovary and lack of metastasis.
• Estrus suppression for one to two estrous 
cycles may benefit bitches with short 
interestrous interval (4 months or less).
• Better breeding management—good 
prognosis for future fertility, unless other 
condition present (more guarded prognosis).
• Antibiotics—for uterine infection; choice 
depends on bacterial culture and sensitivity of 
the uterus or of vaginal discharge during 
proestrus or estrus.
• l-thyroxine—for thyroid insufficiency; 
dogs: 0.01–0.02 mg/kg PO q12h; prognosis 
for future fertility with return to euthyroid 
state guarded.Gonadotropin Therapy
• For induction of ovulation.
• Gonadotropin-releasing hormone (GnRH), 
which causes release of endogenous LH from 
the pituitary, or human chorionic gonadotropin 
(hCG), which has LH-like activity.
• Ovarian cystic disease—GnRH (50  𝜇g/dog 
IM) or hCG (1,000 IU/dog half IV/half IM); 
causes ovulation or luteinization of cystic 
ovarian tissue.
• Estrus induction—diethylstilbestrol 
(5 mg PO q24h for 9 days or until signs of 
proestrus induced); bromocriptine (20  𝜇g/kg 
PO q12h for 21 days); cabergoline (5  𝜇g/kg 
PO q24h for up to 30 days or until signs of 
proestrus induced); deslorelin (2.1 mg 
implant, Ovuplant®; placed in vestibule): 
must have serum progesterone <0.5 mg/mL 
at start; implant removed after ovulation 
confirmed with serum progesterone  
>10 ng/mL.
• Estrus suppression—megestrol acetate 
(2 mg/kg PO q24h for 8 days if begun within 
first 3 days of proestrus, or 0.5 mg/kg PO 
q24h for 32 days if begun in anestrus) or 
mibolerone (dose dependent on bodyweight; 
30 𝜇g PO q24h for dogs weighing 0.5–12 kg; 
60 𝜇g PO q24h for 12–23 kg; 120  𝜇g PO 
q24h for weight 23–45 kg; 180  𝜇g PO q24h 
daily for dogs weighing >45 kg and for 
German shepherd dogs and related breeds 
and crossbreds).
• T reatment with progestins, including 
megestrol acetate, contraindicated in bitches 
with cystic endometrial hyperplasia or history 
of progesterone-dependent disease.
• T reatment with mibolerone contraindicated 
in Bedlington terriers and other breeds with 
familial liver disease.
• All hormonal therapies contraindicated in 
potentially pregnant bitches.
  FOLLOW-UP
• Hypothyroid dogs—recheck thyroid 
function after 1 month of supplementation.
• Ultrasonography—to definitively diagnose 
pregnancy; monitor gestation.
• Progesterone assay.  MISCELLANEOUS
Karotype testing can be performed by 
Molecular Cytogenetics Laboratory, Texas 
A&M University, or Veterinary Genetics 
Laboratory, UC Davis.
• Infertility caused by endocrinopathy—
hypothyroidism, hyperadrenocorticism.
• Bitches with vaginal anatomic abnormality—  
persistent or recurrent urinary tract disease or 
vaginitis.
B. canis  infection—organism is less readily 
shed if affected animals are gonadectomized; 
stress good hygiene.
SEE ALSO
• Abortion, Spontaneous (Early Pregnancy 
• Infertility, Male—Dogs.
• Ovarian Remnant Syndrome.
• Vaginal Hyperplasia and Prolapse.
• Vaginal Malformations and Acquired 
Lesions.
Clinical approach to infertility in the bitch. 
In: Johnston SD, Root Kustritz MV, 
Olson-Schultz PN, Canine and Feline 
Theriogenology. Philadelphia, PA: 
Saunders, 2001, pp. 257–273.
Meyers-Wallen VN. Abnormal and unusual 
estrous cycles. Theriogenology 2007, 
68:1205–1210.
Authors  Lynda M.J. Miller and Maria 
Soledad Ferrer
available onlineInfertility, Female—Dogs  (continued)

Canine and Feline, Seventh Edition  769
I
Infertility, Male—Dogs
  BASICS
• Diminished or absent fertility; does not 
imply sterility.
• Results from wide range of problems that 
prevent delivery of sufficient numbers of 
normal spermatozoa to fertilize ovulated, 
mature oocytes in the bitch.
• Spermatogenesis—formation and develop -
ment of spermatozoa from spermatogonia to 
mature spermatozoa; coordinated, hormonally 
controlled, cyclic process; testicular problems 
require at least 70 days for recovery; epididy -
mal problems require up to 10–14 days.
• Azoospermia—no spermatozoa in ejaculate.
• Oligozoospermia—low number of spermatozoa.
• Teratospermia—high number of 
abnormally shaped spermatozoa.
• Asthenospermia—reduced motility.
• Primary causes—impaired or arrested 
spermatogenesis, blockage of excurrent ducts, 
genitourinary inflammation, testicular 
neoplasia, environmental stress, congenital 
abnormality, endocrine abnormality.
• Nervous.
GENETICS
• Heritable component should be considered 
for autoimmune orchitis as cause of 
azoospermic infertility.
• Cryptorchidism—heritable, sex-limited 
polygenic autosomal recessive trait in dogs; 
inguinal/umbilical hernias, patellar luxation, 
preputial and penile problems.
• Alpha-L-fucosidase deficiency—storage 
disorder causing acrosomal dysgenesis.
• Primary ciliary dyskinesia—congenital 
abnormality of ciliary ultrastructure; absent, 
irregular, or asynchronous motility patterns of 
all ciliated cells; diagnosed by electron 
microscopy of spermatozoa.
• Hypothyroidism—effect on male fertility 
probably minimal.
T rue incidence unknown; likely increased 
with inbreeding.
Species
Dog
Relatively higher prevalence of specific 
problems in breeds with small genetic pool or 
intensive inbreeding.Mean Age and Range
SIGNS
General complaint—no puppies produced; 
whelping rate <75% when bred with correct 
timing to fertile bitches.
• Age of testicular descent.
• Age at first attempted mating.
• Temperament (high-strung).
• Libido and breeding behavior.
• Frequency and number of matings.
• Method used to time breedings.
• Type of semen used for breeding (fresh, 
fresh-extended, chilled-extended, frozen).
• Handling of semen and route of 
insemination.
• Litter size(s).
• Familial history of infertility.
• Coefficient of inbreeding.
• Fertility status of bitches.
• Brucella canis  status of all breeding animals.
• Current and previous drug and dietary 
therapies, especially corticosteroids and 
steroid hormones.
• Previous medical or surgical illnesses.
• Sheath and penis—palpate to identify 
masses or adhesions.
• Nonerect penis—exteriorize to identify 
lesions of superficial mucosa and damage to 
os penis.
• Testes and epididymides—palpate and 
examine, note size and symmetry of epididy -
mides relative to testes.
• Internal urethra and prostate—digital rectal 
palpation to determine location, size, and 
symmetry.
CAUSES
Incorrect timing of breeding—most common 
cause.
• Chromosomal abnormalities: XXY 
syndrome and XX disorder of sexual 
development (see Sexual Development 
Disorders).
• Germinal cell aplasia—biopsy reveals 
“Sertoli cell only” syndrome.
• Segmental aplasia of epididymis or vas 
deferens—oligospermia (unilateral) or 
azoospermia (bilateral).
Acquired
• Incomplete ejaculation—unfamiliar 
surroundings; slippery flooring; no estrous 
bitch; dominant owner or bitch present.
• Obstruction of efferent ducts, epididymides, 
or ductus deferens—azoospermia if bilateral; 
sperm granuloma, spermatocele, acute 
inflammation, chronic inflammatory stenosis, 
segmental aplasia, neoplasia, vasectomy, 
attempts to tack testes into scrotal location.• Hyperthermia/heat stroke.
• Inflammation or infection of testes—
especiall y Escherichia coli ; requires prompt 
and aggressive treatment to prevent 
• Hypothyroidism—role unclear; may be 
associated with decreased libido.
• Hyperprolactinemia—role unclear; 
associated with azoospermia.
• Hyperadrenocorticism—testicular atrophy 
and oligospermia; probably reversible.
• Drugs—parasiticides, corticosteroids, 
anabolic steroids, estrogens, androgens, 
progestogens, gonadotropin-releasing 
hormone (GnRH) agonists/antagonists, 
ketoconazole, amphotericin B: may interfere 
with or interrupt spermatogenesis.
• Environmental toxins—endocrine-
disrupting contaminants can affect 
hypothalamic-pituitary-gonadal axis and 
gonadal steroidogenesis.
• T rauma, testicular neoplasia, systemic 
disease, and ischemia—may cause transient 
infertility or sterility.
• Prostatic disease—can markedly reduce 
semen quality and libido.
• Inbreeding—reduces fertility; reduced-
fertility lines might only be salvaged by 
concerted breeding program and out-crosses 
with highly fertile animals.
• Lymphocytic orchitis—familial in some 
breeds (e.g., beagle and borzoi); affected 
animals may be fertile when young; 
accelerated rate of fertility loss with age.
• Retrograde ejaculation—some retrograde 
flow into bladder normal.
• Congenital disorders affecting reproductive 
function—occur in specific breeds.
• Teaser bitches and stud dogs not tested for 
infectious diseases (e.g., B. canis  and bacterial 
culture of genital tract) before clinical use.
  DIAGNOSIS
Before extensive diagnostic work on male, 
determine that bitches are fertile (previous 
litters) and breedings optimally timed (see 
Infertility, Female—Dogs, and Breeding, 
Timing).
• Brucellosis or prostatitis—variable changes 
in leukogram (normal or leukocytosis) and 
urinalysis (high numbers of leukocytes); 
depends on time course of infection; 
false-negative Brucellosis test possible, 
antibiotic therapy may cause false negative.
• Systemic illness—may impair reproductive 
function, but infertility usually not primary 
complaint.

770  Blackwell’s Five-Minute Veterinary Consult  
IOTHER LABORATORY TESTS
Endocrine Profile
• Resting testosterone—normal, intact dogs, 
0.4–10 ng/mL (1–4 ng/mL common range).
• Primary testicular failure—low testosterone 
and high follicle-stimulating hormone (FSH) 
and luteinizing hormone (LH).
• Germinal compartment failure—normal 
testosterone and high FSH; FSH high due to 
loss of inhibin secretion from Sertoli cells.
• Hypogonadism—low testosterone, FSH, 
and LH.
• Thyroid function—evaluated by baseline 
T3, T4, thyroid-stimulating hormone 
concentration (see Hypothyroidism).
• B. canis —screen with 2-mercaptoethanol 
rapid slide agglutination test (2-ME-RSAT); 
confirm with agar gel immunodiffusion test 
(AGID).
IMAGING
Ultrasonography—identify lesions that alter 
testicular and epididymal architecture (e.g., 
neoplasia, spermatocele, orchitis, epididymitis); 
evaluate prostate gland for hyperplasia, chronic 
prostatitis, cyst, abscess, or neoplasia (see 
Prostate Disease in the Breeding Male Dog).
Breeding Soundness Examination
• Must always consist of two semen collections.
• Sperm-rich and prostatic portions of 
ejaculate—collect as separate fractions by use 
of sterile artificial vagina and sterile, graduated, 
nontoxic plastic tubes, in presence of estrous 
bitch.
• Sperm-rich fraction—assess volume, 
concentration, motility, and morphologic 
characteristics of sperm cells; qualitative and 
quantitative cultures.
• Prostatic fraction and urine—cytologic 
examination; qualitative and quantitative 
cultures.
• Culture results—must be correlated with 
clinical and cytologic evidence of active 
infection; inflammation present if >3–5 white 
blood cells/hpf observed (especially sperm-
rich fraction).
• If prostatic fraction indicates infection—
reevaluate by other sampling techniques that 
avoid contamination from penile mucosa and 
prepuce; negative cytology possible with 
chronic prostatitis.
• Azoospermic or oligospermic ejaculate—
recollect 1 hour later and again on several 
occasions before confirming infertility.
Epididymal Markers
Alkaline phosphatase (ALP) activity in 
seminal fluid—normal 8,000–40,000 U/mL; 
epididymal in origin; may indicate obstruc-tion if <5,000 U/mL and complete ejaculate 
obtained; pathologic effects of obstruction 
more easily seen from ALP concentration if 
ALP performed on two ejaculates collected 1 
hour apart.
Testicular biopsy—determines degree of 
spermatogenesis and integrity of blood–testis 
barrier; differentiates obstruction of efferent 
ducts from testicular hypoplasia and 
degeneration; allows informed prognosis.
  TREATMENT
ACTIVITY
• Restrict if activity results in hyperthermia.
• No restriction for other causes.
DIET
Ensure adequate diet and mineral supplemen-
tation; avoid supplementation of products 
containing excessive or undefined amounts of 
steroid hormones, e.g., extracts of testes, 
ovaries, and adrenals; phytoestrogens.
• Return to function may require at least 
70 days from correction of identified 
cause(s).
• Stress patience and check patient regularly 
to ensure condition is not worsening.
• Emphasize potential role of heritable 
Re-anastomosis of blocked excurrent 
epididymal ducts (vasectomies) has been 
successful for reestablishment of sperm 
• Antibiotics as indicated by culture and 
• Pseudoephedrine—to treat retrograde 
ejaculation (used with limited success in 
men): 4–5 mg/kg PO q8h, or 1h and 3h 
before collection.
• Phenylpropanolamine—4–8 mg/kg PO 
q24h starting 5 days prior to collection.
• T rimethoprim-sulfas—contraindicated if 
predisposed to keratoconjunctivitis sicca, can 
induce thrombocytopenia.
• Chloramphenicol—associated with 
anorexia and vomiting.  FOLLOW-UP
Recheck at intervals that take into account 
length of spermatogenic cycle (70 days) but 
frequent enough to allow detection of 
deteriorating condition.
Avoid exposure to environmental temperature 
extremes.
50–60% return to fertility after diagnosis and 
appropriate treatment.
• Brucellosis—discospondylitis, polyarthritis, 
posterior paresis, fever, uveitis.
• Prostatic disease—obstipation, locomotor 
difficulties, fever, hematuria, pollakiuria, 
dysuria.
• Lymphocytic orchitis—lymphocytic 
• Daily sperm output and morphologically 
normal sperm cells decline with age.
• Difficult to assess effect of age alone on 
• Most old, infertile dogs have concurrent 
diseases (e.g., systemic or prostatic disease, 
testicular neoplasia, osteoarthritis) that have 
documented effects on fertility or libido.
• 2-ME-RSAT = 2-mercaptoethanol rapid 
slide agglutination test.
• AGID = agar gel immunodiffusion test.
• FSH = follicle-stimulating hormone.
Kolster K. Evaluation of canine sperm and 
management of semen disorders. Vet Clin 
Small Anim Pract 2018, 48:533–545.
Author  Richard A. Fayrer-Hosken
available onlineInfertility, Male—Dogs  (continued)

Canine and Feline, Seventh Edition  771
IInflammatory Bowel Disease
  BASICS
A group of chronic enteropathies character -
ized by persistent or intermittent gastrointesti -
nal (GI) signs with histopathologic evidence 
of intestinal inflammation. Inflammatory 
bowel disease (IBD) is generally categorized 
by the predominant mucosal cellular infiltrate, 
such as lymphocytic-plasmacytic, eosinophilic, 
or granulomatous enteritis.
• Poorly understood but likely due to complex 
interplay between mucosal immunity and 
environmental factors (i.e., dietary and bacterial 
antigens) in genetically susceptible dogs; aberrant 
host immune responses are likely triggered by 
antigens derived from resident microbiota. 
• Damage results from elaboration of cytokines, 
release of proteolytic and lysosomal enzymes, 
complement activation secondary to immune 
complex deposition, and generation of oxygen 
free radicals. • Host genetic susceptibility 
involving defects in innate immunity is 
suspected in dogs, and possibly cats.
• GI. • Hepatobiliary. • Hemic/lymphatic/
immune—rarely. • Musculoskeletal—rarely. 
• Ophthalmic—rarely. • Respiratory—rarely. 
• Skin/exocrine—rarely.
GENETICS
Defects in host susceptibility genes have been 
identified in German shepherd dog, boxer, 
and soft-coated wheaten terrier.
IBD is most common histopathologic diagnosis 
in dogs and cats with chronic GI signs in which 
other causes have been eliminated through 
clinical trials and diagnostic testing.
N/A
Species
• Increased risk in German shepherd, boxer, 
and soft-coated wheaten terrier, in addition to 
breed-specific forms described elsewhere. 
• Siamese cats may be predisposed.
Most common in middle-aged animals, but 
younger animals may be affected.
N/A
SIGNS
• Intermittent or persistent chronic GI signs 
(>3 weeks’ duration). • May include vomiting, small/large bowel diarrhea, decreased appetite, 
and/or weight loss. • Severe IBD may cause 
protein-losing enteropathy (PLE) in dogs.
• Vary from apparently healthy to a thin, 
lethargic animal. • Poor hair coat with chronic 
disease and nutritional deficiencies. • Abdominal 
palpation may reveal pain, thickened bowel 
loops, and mesenteric lymphadenopathy 
(especially in cats). • Ascites may occur in dogs 
with PLE. • Hematochezia, fecal mucus, and 
tenesmus seen with colonic involvement.
CAUSES
Pathogenesis unknown but most likely multi -
factorial, involving complex interactions 
between host genetics, mucosal immunity, and 
environmental (diet, intestinal bacteria) factors.
• Adherent and invasive Escherichia coli  has been 
associated with granulomatous colitis in dogs.
• Giardia , Salmonella , Campylobacter , and 
resident microbiota have been implicated.
Dietary Agents
Meat proteins, milk proteins, gluten (wheat), 
and additives are all proposed causative 
agents, likely playing an important role.
Genetic Factors
• Some forms of IBD more common in certain 
breeds. • Defects in innate immunity (e.g., 
mutations in TLR2 , TLR5 , and nod2 as seen in 
German shepherd dogs) that perturb mucosal 
homeostasis may predispose individual to IBD.
Current hypotheses suggest that IBD is 
multifactorial disorder conditioned by genetic, 
immunologic, and environmental factors.
  DIAGNOSIS
• Cats—hyperthyroidism, intestinal neoplasia 
(especially small cell lymphoma), adverse food 
reactions, feline infectious peritonitis and other 
viral infections (e.g., feline leukemia virus [FeLV] 
and feline immunodeficiency virus [FIV]), renal 
and hepatic insufficiency, exocrine pancreatic 
insufficiency, intestinal parasitism, and antibiotic-
responsive diarrhea (ARD) are primary differentials. 
• Dogs—intestinal neoplasia, motility disorders, 
adverse food reactions, lymphangiectasia, exocrine 
pancreatic insufficiency, intestinal parasitism, and 
ARD are primary differentials.
• Often unremarkable; these tests more often 
serve to eliminate other differential diagnoses.
• Anemia of chronic disease; mild leukocytosis ± 
left shift sometimes seen with mucosal disruption 
(e.g., erosions); mild eosinophilia may be seen 
with eosinophilic enteritis, food allergy, and 
intestinal parasites among other causes. • Cats may show alterations in serum total protein (i.e., 
hyperproteinemia) and albumin concentrations, 
with increased liver enzyme activities. 
• Hypoproteinemia more common in dogs than 
cats. • Cobalamin deficiency in both dogs and 
cats with involvement of ileum.
• Useful to eliminate other differentials.
• Dogs—evaluation of exocrine pancreatic 
function: canine trypsin-like immunoreactiv-
ity (cTLI); serology for pancreatitis: canine 
pancreatic lipase activity (Spec cPL), and 
serum cobalamin and folate assays to localize 
small intestinal disease. • Cats—T4 and 
FeLV/FIV serology; fasting serum TLI (if 
exocrine pancreatic insufficiency suspected); 
serology for pancreatitis (Spec fPL), and 
small intestinal disease.
IMAGING
• Survey abdominal radiographs—usually 
unremarkable. • Barium contrast studies—
may reveal mucosal abnormalities and 
thickened bowel loops; normal findings do 
not eliminate possibility of IBD. 
• Ultrasonography—may indicate increased 
intestinal wall thickness (particularly 
muscularis propria and submucosal layers) 
and mesenteric lymphadenopathy; however, 
these abnormalities not specific for IBD.
• Perform elimination dietary trial to rule out 
adverse food reactions; if GI signs resolve within 
2 weeks, then diagnosis of adverse food reaction 
is made. • Perform fecal testing for nematode 
and protozoal parasites; treat for Giardia  spp. 
and endoparasitic infection with fenbendazole 
(50 mg/kg for 5 days). • Definitive diagnosis of 
IBD requires intestinal biopsy and histopathology, 
usually obtained via GI endoscopy; WSAVA 
guidelines should be used to define severity of 
mucosal inflammation. • Laparotomy indicated 
if GI endoscopy unavailable or to collect 
full-thickness mucosal specimens; always be sure 
to collect ileal biopsies . • Use scoring indices 
(canine inflammatory bowel disease activity 
index) to define clinical severity and assess 
Morphologic evidence of mucosal inflamma -
tion including epithelial changes, architectural 
distortion (e.g., erosion/ulceration, crypt 
hyperplasia, fibrosis, loss of colonic goblet 
cells), and increased lamina propria cellularity. 
Histopathologic guidelines for defining severity 
of GI inflammation have been described.
  TREATMENT
Outpatient, unless patient is debilitated from 
dehydration, hypoproteinemia, or cachexia.

772  Blackwell’s Five-Minute Veterinary Consult  
INURSING CARE
• If patient is dehydrated or must have food 
restricted because of intractable vomiting, any 
balanced crystalloid fluid is adequate (for a 
patient without concurrent disease); otherwise, 
select fluids on basis of secondary diseases. 
• If severe hypoalbuminemia from PLE, 
consider use of colloids.
ACTIVITY
DIET
• Feed novel intact protein or hydrolysate 
elimination diet to help reduce intestinal 
inflammation. • Fiber supplementation (e.g., 
fermentable fiber such as pumpkin, 
Metamucil®) suggested in dogs and cats with 
colitis. • Fish oil (n-3 fatty acids) as free 
radical scavenger to reduce inflammation. 
• Probiotics may be of benefit in some 
animals but clinically unproven at this time; 
must be given continuously over several weeks 
for potential benefit to be realized.
• Emphasize that IBD is not cured but is 
controllable in most instances. • Relapses are 
common; clients should be patient during the 
various food and medication trials that are 
often necessary to control the disease.
Surgery only indicated for collection of intestinal 
biopsies in dogs and intestinal and/or liver, 
pancreatic and/or mesenteric biopsies in cats.
• Evidence-based data indicate glucocorticoids 
are effective drugs for inducing remission in 
majority of dogs and cats; use prednisone or 
prednisolone in dogs at 1–2 mg/kg PO daily 
for 21 days to induce remission, then taper 
dose by 25% every 2 weeks.
• Dogs weighing >30 kg will require lower 
steroid dosage to provide comparable clinical 
efficacy; this will also reduce adverse effects; 
dose large dogs by body surface area . • T reat cats 
with oral prednisolone at 1–2 mg/kg for 
14–21 days, then taper as above; avoid 
glucocorticoids in cats with diabetes mellitus 
and those with history of adverse effects. 
• Budesonide may be used to minimize 
adverse steroid effects and maintain remission 
in some dogs and cats; dosage ranges dogs: 
1–3 mg/m2 daily; cats: 1 mg/day. • Correct 
hypocobalaminemia by weekly parenteral 
cobalamin injections for first 6 weeks and 
thereafter every 2–3 weeks or as needed based 
on repeat testing of cobalamin concentrations; 
oral cobalamin therapy requires daily admini -
stration; antibiotics (metronidazole, tylosin) 
generally not indicated for treatment of IBD; 
these drugs may cause significant disruption to gut microbiota even after administration 
discontinued. • Some evidence that oral 
cyclosporine is of value in dogs with steroid-
refractory disease and PLE; dose at 5 mg/kg 
PO daily for 4–6 weeks or as needed to induce 
remission. • Use of other immunosuppressive 
drugs, including azathioprine, chlorambucil, 
leflunomide, or mycophenolate, has been 
reported. • Empirical deworming with 
fenbendazole (50 mg/kg PO q24h for 5 days). 
• Fecal microbiota transplant anecdotally 
effective in cases of refractory IBD; however, 
clinical trial data yet to be reported.
Based on concurrent disease.
See Drug(s) of Choice.
  FOLLOW-UP
• Periodic (q2–4 weeks) physical and laboratory 
evaluations may be necessary until the patient’s 
condition stabilizes; serum albumin provides 
important prognostic information in dogs; 
serum cobalamin deficiency will delay complete 
clinical recovery in both dogs and cats. 
• Monitor serum cobalamin concentrations in 
hypocobalaminemic dogs and cats. • No other 
follow-up may be required except yearly physical 
examinations and assessment during relapse.
N/A
Dehydration, malnutrition, adverse drug 
reactions, hypoproteinemia, hypocobalamine-
mia, anemia, and diseases secondary to 
therapy.
• Generally good to excellent short-term 
prognosis. • Poor long-term prognosis in 
dogs with IBD has been associated with 
severe clinical disease, marked endoscopic 
(duodenal) abnormalities, ascites, and 
hypoalbuminemia; long-term prognosis worse 
compared to food-responsive diarrhea and 
ARD, other forms of canine chronic 
• See discussion under specific diseases. 
• Cats may demonstrate concurrent inflammatory lesions in the liver and/or 
pancreas (“triaditis”).
Some differentials more likely in younger 
individuals (i.e., intestinal parasitism vs. 
N/A
Counsel clients about breeding and monitor-
ing for appearance of other diseases.
SYNONYMS
None
SEE ALSO
• Colitis, Histiocytic Ulcerative.
• Gastroenteritis, Eosinophilic.
• Immunoproliferative Enteropathy of Basenjis.
• ARD = antibiotic-responsive diarrhea. 
• cPL = canine pancreatic lipase. • FeLV = 
feline leukemia virus. • FIV = feline 
immunodeficiency virus. • fPL = feline 
pancreatic lipase. • GI = gastrointestinal. 
= protein-losing enteropathy. • TLI = 
trypsin-like immunoreactivity.
http://www.vin.com/VIN.plx
178:368.
Day MJ, Bilzer T, Mansell J, et al. International 
standards for the histopathological diagnosis 
of gastrointestinal inflammation in the dog 
and cat: a report from the World Small 
Animal Veterinary Association 
Gastrointestinal Standardization Group. 
J Comp Pathol 2008, Suppl 1:S1–S43.
Makielski K, Cullen J, O’Connor A, Jergens 
AE. Narrative review of therapies for 
chronic enteropathies in dogs and cats. J Vet 
Intern Med 2019, 33(1):11–22.
Simpson KW, Jergens AE. Pitfalls and 
progress in the diagnosis and management 
of canine inflammatory bowel disease. Vet 
41(2):381–398.
available onlineInflammatory Bowel Disease  (continued)

Canine and Feline, Seventh Edition  773
IInfluenza
  BASICS
OVERVIEW
• An acute to subacute contagious viral 
disease with an almost exclusive respiratory 
manifestation caused by influenza viruses.
• Canine influenza viruses (CIV) are influenza 
type A viruses that developed from equine 
(H3N8, USA) or avian (H3N2; East Asia) 
influenza viruses. Although the viruses originated 
in other species, the H3 viruses are considered 
“canine influenza viruses” as they are now 
transmissible dog to dog. Influenza H7N2 is an 
avian influenza A virus that was documented in 
shelter cats. H1N1 human pandemic influenza 
is also capable of infecting dogs and cats, but 
there is no evidence of transmission.
• Natural route of infection is airborne 
particles or oral contact with contaminated 
surfaces. Replication of the virus appears to 
be restricted to epithelial cells of the upper 
and lower airways, with possible involvement 
of alveolar macrophages. Antibody response 
detectable by 8 days post infection and titers 
remain detectable for >1 year. Protective 
immune responses have not been defined.
• H3N8 CIV activity was first detected in 
racing greyhounds in the United States in 
2004 and has subsequently been identified in 
dogs across the country.
• H3N2 CIV was detected in South Korea in 
2007, but existed in China several years earlier; 
genetic lineage is of avian origin and probably 
arose in East Asia.
• H3N2 CIV infection causes more severe 
clinical signs, is more easily transmissible, and 
is shed for a longer period than H3N8 CIV.
• Natural infections of H3N8 CIV currently 
limited to dogs; H3N2 virus is capable of 
infecting dogs and cats; H7N2 has infected 
shelter cats.
• All dogs and cats are susceptible to 
infection; there are no known age, breed, or 
sex restrictions on susceptibility.
SIGNS
• 60–80% of infected dogs develop clinical 
signs.
• Incubation period 2–4 days post infection.
• Modest febrile response 39.4–40 °C 
(103–104 °F) 3–6 days post infection.
• Clear nasal discharge, which can progress to 
thick, mucoid discharge, most frequently 
caused by secondary bacterial colonization.
• More severe form of disease shows higher body 
temperatures with development of pneumonia 
and tachypnea 6–10 days post infection.
• Many dogs develop a cough that can last 
for several weeks.
• Respiratory infection caused by influenza 
viruses.• Most cases have a history of group housing 
in kennels, day care centers, and rescue 
shelters, or contact with animals that have 
recently been in group housing or social 
settings such as dog shows.
  DIAGNOSIS
• On an individual basis, early signs of 
influenza are indistinguishable from signs of 
kennel cough complex.
• Distinction from typical respiratory pathogens 
of dogs is found in group settings in which 
60–80% of dogs can show clinical signs.
• Later in disease course—pneumonia may 
develop with or without secondary bacterial 
• Generally unremarkable.
• CBC may reflect stress initially, then 
bacterial pneumonia later in disease 
(leukocytosis, left shift).
N/A
• Matrix gene reverse transcriptase 
polymerase chain reaction (RT-PCR) test—
most reliable and preferred test; can detect 
agent in acute phase of disease (1–7 days post 
onset of clinical signs) in nasal swab.
• Viral isolation—possible early (~first 3 
days) in infection.
◦ PCR and viral isolation can be negative if 
collected too late in infection.
◦ Serologic tests for H3N8 will not detect 
H3N2 and vice versa; must test for each 
separately.
• Hemagglutination inhibition test—preferred 
serologic test; acute and convalescent titers 
optimal; since most dogs have no circulating 
CIV antibodies, antibodies detected in serum 
more than 7 days post onset of clinical signs 
determine exposure to CIV.
• Antigen-capture ELISA tests gave 
unacceptable levels of false negatives with 
H3N8 infections, but higher viral loads with 
H3N2 give acceptable results if testing done 
early in course of infection.
Primary lesion caused by infection is 
destruction of ciliated epithelial cell layer in 
upper airways with extension into lungs. 
Areas of lung consolidation can be found 
6–10 days post infection.
  TREATMENT
• Infected animals should be isolated to 
prevent infection of other animals.• Contagious period for H3N2 CIV extends 
approximately 2 weeks after onset of clinical signs.
• Continued coughing of affected animal is 
not a sign of virus shedding.
• Strongly recommend treating uncomplicated 
cases as outpatients to prevent hospital 
contamination.
• Only hospitalize those with pneumonia 
that require IV fluid or oxygen support.
• Enforced rest—for at least 14–21 days 
(uncomplicated cases); 2 months in cases of 
• Antiviral drugs have not been tested for efficacy.
• Antibiotics to control secondary bacterial 
infections recommended if fever, lethargy, or 
inappetence accompany mucopurulent nasal 
discharge—amoxicillin, amoxicillin–
clavulanic acid, and doxycycline are empiric 
first-line options for mild cases.
• Clinical pneumonia—first-line recommen-
dations include parenteral administration of 
fluoroquinolone and penicillin (ampicillin) or 
clindamycin initially until antimicrobial 
culture and sensitivity available.
◦ Resistant bacteria—important to culture and 
establish bacterial sensitivity; consider inherent 
resistance of Mycoplasma to penicillins and 
cephalosporins; for organisms resistant to 
first-choice antibiotic therapies above, consider 
aminoglycosides (gentamicin or amikacin, 
contraindicated in animals with renal 
dysfunction, dehydration), cephalosporins 
(cephalexin, cefazolin, cefadroxil, cefoxitin, 
cefovecin); see Suggested Reading.
◦ In absence of controlled studies on 
efficacy, inhalational antimicrobial therapy 
• In animals treated for pneumonia—recheck 
patient and radiographs after 10–14 days to decide 
whether continued antibiotic therapy indicated; 
optimal duration of therapy for pneumonia 
unknown; shorter courses of antibiotics (as used in 
humans with pneumonia) than traditionally 
recommended 4–6 weeks may be effective.
• Cough suppressants (butorphanol or 
hydrocodone bitartrate)—often effective in 
suppressing dry nonproductive cough; cough 
suppression counterproductive in animals 
with pneumonia.
• Bronchodilators (theophylline or amino -
phylline)—may relieve wheezing.
  FOLLOW-UP
• If infection established in a kennel, evacuate 
kennel for 1–2 weeks and disinfect with sodium 
hypochlorite (1 : 30 dilution), chlorhexi  dine, or 
benzalkonium; influenza virus can live on hard 
surfaces for up to 24 hours.

774  Blackwell’s Five-Minute Veterinary Consult  
I• Uncomplicated cases should resolve within 
10–14 days; if patient continues to cough 
beyond 14 days, further diagnostics indicated.
• Mortality rate highly variable and likely linked 
to degree of secondary bacterial infection, strain 
of virus, and intensity of veterinary care.
• Currently there are licensed influenza 
vaccines for use in dogs that cover H3N8, 
H3N2, or both. There are no licensed 
vaccines for cats.
• Risk thought to be low; however, influenza 
viruses mutate rapidly and outbreaks in dogs and cats monitored for this potential; one 
person documented to develop infection with 
H7N2 working with cats in shelter outbreak.
• Cats can be experimentally infected with 
H3N8 CIV; H7N2 virus was isolated from 
cats in an animal shelter.
• H3N2 virus can also infect ferrets, guinea 
pigs, and mice.
• CIV = canine influenza virus.
https://www.avma.org/resources-tools/
animal-health-and-welfare/canine-influenza Suggested Reading
Dubovi EJ, Njaa BL. Canine influenza. Vet 
Clin Small Anim 2008, 38:827–836.
of respiratory tract disease in dogs and cats: 
Antimicrobial Guidelines Working Group 
of the International Society for Companion 
Animal Infectious Diseases. J Vet Intern 
Med 2017, 31:279–294.
Author  Edward J. Dubovi
Consulting Editor  Amie KoenigInfluenza  (continued)

Canine and Feline, Seventh Edition  775
I
Insoluble Oxalate Plant Toxicosis
  BASICS
OVERVIEW
• Over 200 species of plants contain 
insoluble oxalate crystals.
• Most houseplants are in the Araceae family; 
many are found in homes and offices.
• Common names vary; scientific names 
must be used for accurate identification.
• Insoluble oxalate crystals are not absorbed 
systemically, and signs are often self-limiting.
• Signs are generally limited to irritation of 
oral mucosa; other signs occur more rarely.
• Dieffenbachia  spp. (dumbcane) ingestion by 
dogs and cats has been associated with more 
serious outcomes, including death.
• Cats ingesting Philodendron  spp. may 
exhibit more severe clinical signs.
• Common plants include:
◦ Aglaonema commutatum  (Chinese 
evergreen).
◦ Anthurium  spp. (flamingo flower).
◦ Arisaema amurense  (Jack-in-the-pulpit).
◦ Dieffenbachia  spp. (dumbcane).
◦ Epipremnum  spp. (pothos, devil’s ivy, 
variegated philodendron).
◦ Monstera deliciosa  (fruit salad plant).
◦ Philodendron  spp. (sweetheart vine, fiddle 
leaf).
◦ Schefflera actionphylla  (umbrella plant).
◦ Spathiphyllum  spp. (peace lily).
◦ Syngonium  spp. (arrowhead vine).
◦ Zantedeschia  spp. (calla lily).
• Indoor cats and dogs primarily, although 
pets may be exposed by houseplants moved 
outside during summer months.
• Dogs tend to chew and destroy the entire 
plant; cats nibble on leaves.
• May occur more often in younger pets that 
are bored or inquisitive.
SIGNS
• Rapid onset, often within minutes of 
exposure.
• Oral—vocalization, pawing at muzzle, head 
shaking, hypersalivation, edema of lips, 
tongue or pharynx; rarely gagging, choking, 
• Ocular—pawing at eyes, photophobia, 
conjunctival swelling.
• Respiratory— rarely , dyspnea from 
pharyngeal swelling and inflammation.
• Plants in environment.
• Insoluble oxalate crystals are arranged in 
bundles called raphides that are contained in 
idioblasts within plant stems and leaves.
• Chewing or biting on plant material 
releases crystals from stems and leaves until 
idioblast is emptied.• Crystals act as miniature pins or mechanical 
irritants to mucous membranes, but are not 
absorbed systemically.
• Potential for chemical irritation with release 
of prostaglandins, histamine, proteolytic 
enzymes.
  DIAGNOSIS
• Caustic agents (alkalis and acids in 
household products; drain cleaners).
• Other agents causing oral irritation 
(capsaicin, detergents, topical spot-on flea 
and tick products.
• Quaternary ammonium compounds ( >2% 
in cats).
• Stinging nettle ( Urtica dioica ) ingestion.
• Systemic disease-causing oral lesions.
• Rarely performed unless prolonged vomiting.
• CBC, electrolytes, serum chemistry.
N/A
IMAGING
N/A
• Exam of oral cavity including visualization 
of pharynx.
• Fluorescein ophthalmic stain if ocular signs 
are present.
• Death rarely occurs.
• Few cases with severe erosive, ulcerative 
glossitis; oropharyngeal edema.
  TREATMENT
• Generally limited to supportive care.
• IV fluids if dehydrated from excessive 
salivation or vomiting.
• Oral—irrigation of oral cavity with copious 
amounts of cool fluids; small amounts of 
calcium-containing product (milk, yogurt, 
etc.) to bind oxalate crystals.
• Ocular—lavage for 15 min with tepid 
water.
• Respiratory—endotracheal tube or 
temporary tracheostomy if dyspnea severe.
No specific antidote available.
• Antiemetics as needed:
◦ Maropitant 1 mg/kg SC/PO/IV q24h.◦ Ondansetron 0.1–1mg/kg IV q8–12h.
• GI protectants as needed:
◦ H2 blockers (famotidine, ranitidine).
◦ Omeprazole 0.5–1 mg/kg PO daily.
◦ Sucralfate 0.25–1 g PO q8h.
• Pain medication as needed:
◦ Butorphanol 0.1–0.5 mg/kg IV/IM/SC.
Corticosteroids—use is controversial, but 
dexamethasone phosphate 0.125–0.5 mg/kg 
IV/IM/SC may be useful in severe 
inflammatory conditions.
  FOLLOW-UP
Monitor for signs of dyspnea and respiratory 
Identify plants in household and keep away 
from pets.
• Corneal abrasion or ulcer from pawing at eyes.
• Erosive ulcers in mouth and gastrointestinal 
tract.
• Pharyngeal edema and death (rare).
• Most signs are mild to moderate and of 
short duration, generally lasting 2–4 hours; 
less often signs last 12–24 hours.
• Excellent prognosis as signs are generally 
Young pets are more frequently represented; 
likely due to boredom and inquisitive nature.
Hovda LR. Oxalates – insoluble. In: Hovda 
LR, Brutlag A, Poppenga RH, Peterson K, 
eds. Blackwell’s Five-Minute Veterinary 
Consults Clinical Companion: Small 
Wiley-Blackwell, 2016, pp. 787–796.

776  Blackwell’s Five-Minute Veterinary Consult  
IInsulinoma
  BASICS
Functional pancreatic islet beta-cell tumor 
that secretes insulin, independent of systemic 
• Excessive insulin secretion leads to glucose 
uptake and use by insulin-sensitive tissues and 
reduced hepatic production of glucose, resulting 
in hypoglycemia and associated clinical signs.
• Insulinomas can secrete other hormones, such 
as somatostatin, glucagon, gastrin, pancreatic 
polypeptide, insulin-like growth factor 1 
(somatomedin), and serotonin; however, clinical 
signs are typically associated with hypoglycemia.
• Nervous system abnormalities are typically 
the first clinical signs seen due to the brain’s 
dependence on glucose for energy and lack of 
glycogen stores.
• Hypoglycemia stimulates release of counter- 
regulatory hormones (e.g., glucocorticoids, 
growth hormone, catecholamines, and 
glucagon) that cause adrenal stimulation in an 
effort to raise plasma glucose levels.
• Release of counter-regulatory hormones and 
adrenal stimulation can lead to muscle tremors, 
restlessness, nervousness, and hunger.
• Nervous—seizures, disorientation, 
abnormal behavior, collapse, polyneuropathy/
peripheral neuropathy, posterior paresis, 
ataxia.
• Musculoskeletal—weakness, muscle 
• Gastrointestinal—variable appetite and 
weight.
• Urinary—polyuria, polydipsia.
• Dogs—uncommon.
• Cats—rare.
Species
• Dogs—Labrador retrievers, standard 
poodles, boxers, fox terriers, Irish setters, 
German shepherd dogs, golden retrievers, 
collies.
• Cats—possibly Siamese.
• Dogs—middle-aged to old; mean: 10 years, 
range: 3–14 years.
• Cats—mean: 15 years, range: 12–17 years.
SIGNS
• Often episodic and vague.
• May be related to fasting, excitement, 
exercise, and/or eating.Historical Findings
• Dogs—generalized or focal seizures; 
historical findings may include weakness, 
posterior paresis, collapse, muscle fascicula-
tions, bizarre behavior, lethargy and depres-
sion, ataxia, polyphagia or inappetance, 
weight gain or loss, polyuria and polydipsia, 
and exercise intolerance.
• Cats—seizures, ataxia, muscle fasciculations, 
weakness, lethargy and depression, anorexia, 
weight loss, and polydipsia.
• Usually within normal limits unless in a 
hypoglycemic crisis.
• Obesity may be noted.
• Polyneuropathy is seen rarely in dogs 
(paresis to paralysis, muscle atrophy, and/or 
hyporeflexia).
CAUSES
Many dogs and cats have single insulin-pro-
ducing beta-islet cell carcinoma or adenocar-
cinoma of the pancreas, but 50% or more will 
develop or present with metastasis.
For hypoglycemic episodes—fasting, excite -
ment, exercise, and eating.
  DIAGNOSIS
• Extrapancreatic tumor hypoglycemia—para -
neoplastic hypoglycemia has been documented 
in dogs with tumors including leiomyosarcoma 
and hepatocellular, mammary, and pulmonary 
carcinomas, among others; these tumors 
secrete insulin or insulin-like substances.
• Rule out causes such as insulin overdose, 
neonatal/toy breed hypoglycemia, ingestion 
of oral hypoglycemic agents, hepatic failure, 
sepsis, hypoadrenocorticism, hunting dog 
(exertional) hypoglycemia, and glycogen 
storage diseases.
• Seizures and collapse—consider a variety of 
differentials including cardiovascular, 
metabolic, and neurologic disease.
• Often within normal limits except for 
hypoglycemia ( <65–70 mg/dL in majority of 
patients).
• Normoglycemia does not rule out the 
presence of an insulinoma; a small percentage 
of patients may be intermittently normogly-
cemic, which is thought to be due to counter- 
regulatory hormone production (e.g., 
epinephrine, glucocorticoids, glucagon).
Simultaneous Fasting Glucose 
and Insulin Determinations
• Paired glucose and insulin can often be 
measured without fasting, since hypoglycemia 
is commonly identified at presentation.• If a patient presents for hypoglycemia, 
obtain additional serum for possible insulin 
level evaluation prior to administering 
exogenous dextrose.
• If necessary, patients may be fasted (and 
hospitalized and monitored closely due to the 
risk for hypoglycemia), and serial (q1–2h) 
blood samples collected; when serum glucose 
drops below 60 mg/dL, that sample should be 
analyzed for simultaneous glucose and insulin 
◦ Elevated insulin concentration (>20  μU/
mL) in the face of hypoglycemia—insu-
linoma highly likely.
◦ Insulin concentration within reference 
range (5–20  μU/mL) in the face of 
hypoglycemia—insulinoma probable
◦ Any insulin concentration within 
reference range with concurrent hypo -
glycemia is abnormal; if insulin concentra -
tion below normal limits with hypoglycemia 
then an insulinoma is unlikely, but repeated 
sampling may be necessary.
• Formulas utilizing simultaneous 
hypoglycemic glucose and insulin 
concentrations such as the insulin : glucose 
ratio and the amended insulin : glucose ratio 
have poor specificity.
IMAGING
• Thoracic and abdominal radiography—
helpful for identification of metastatic disease 
and/or extrapancreatic tumor-induced causes 
of hypoglycemia as well as some other 
differential diagnoses.
• Ultrasonography—30–75% of pancreatic 
masses are clearly identified through ultrasono -
graphy; can be used for screening for metastatic 
disease, but relatively insensitive.
• CT—superior technique for detection of 
primary insulinomas in dogs; however, 
false-positive lymph node metastases are 
common.
• Scintigraphy and single proton emission 
computed tomography (SPECT)—intermit-
tently successful in detecting insulinomas.
• Intraoperative ultrasound—widely used for 
gross occult tumor detection in human 
insulinomas; rarely reported in veterinary 
medicine.
Exploratory laparotomy—indicated when 
insulinoma is suspected based on the 
aforementioned physical, biochemical, and/or 
imaging results, but imaging is inconclusive.
• Histopathologically, primary pancreatic 
insulinomas in dogs are either beta-islet cell 
carcinomas or adenocarcinomas and 
occasionally adenomas, although dogs with 
adenomas may subsequently develop 
• In cats, most insulinomas are malignant 
with metastasis common.

Canine and Feline, Seventh Edition  777
I
• In both species, metastatic disease is frequently 
noted in the liver, mesentery, and regional 
lymph nodes, and appears histopathologically 
similar to the primary tumor.
  TREATMENT
• Hospitalize for workup and surgery.
• Outpatient if the owner declines surgery 
and the patient is not clinically hypoglycemic.
Close monitoring for recurrence of signs 
associated with hypoglycemia is indicated, 
especially as most hospitalized patients become 
refractory to glucose supplementation and 
require increasing dosages.
ACTIVITY
DIET
• Feed four to six (or more) small meals a day.
• Food should be high in protein, fat, and 
complex carbohydrates and low in simple 
sugars.
Client should be educated about the signs of 
hypoglycemia and seek immediate attention if 
they occur.
• Surgical management improves prognosis 
over medical therapy alone.
• Medical management is important before 
exploratory laparotomy; most patients respond 
well to frequent small feedings and corticosteroids; 
in refractory cases, IV fluids containing 2.5–5% 
dextrose and/or glucagon may be necessary.
• Objectives include confirmation of 
diagnosis, identification of extrapancreatic 
metastases or other disease, and removal of as 
much cancerous tissue as possible.
• At surgery, most insulinomas can be 
visualized and/or palpated; if a pancreatic mass 
cannot be found, intraoperative ultra  sound 
may be beneficial.
• Approximately 15% of dogs have multiple 
primary insulinomas, so always examine the 
entire pancreas.
• Biopsy regional lymph nodes and carefully 
evaluate the liver (and other abdominal contents) 
with biopsy of any abnormalities; 40–50% of 
dogs will have metastasis; in one study, of 14 
dogs suspected to have extrapancreatic metastasis 
from a primary pancreatic insulinoma, only 8 
(57%) had histologic evidence of metastasis; 
therefore, the presence of what appears to be 
metastasis should be biopsied and not automati -
cally lead to intraoperative euthanasia.
• Insulinoma can be classified as stage I 
(confined to the pancreas); stage II (regional 
lymph node metastasis present); or stage III 
(distant metastasis present).• Postoperative complications include 
pancreatitis, persistent hypoglycemia 
secondary to incomplete removal of the 
primary tumor or metastatic disease, and 
diabetes mellitus (DM). DM is thought to 
occur secondary to atrophy of remaining 
normal beta-islet cells.
• 50% dextrose (0.5 g/kg IV diluted 1 : 3, 
slowly over 1–3 min)—for emergency control 
of hypoglycemic episodes; once hypoglycemic 
signs abate, IV fluid therapy with 2.5–5% 
dextrose added to an isotonic crystalloid 
solution should be administered (dextrose 
may be increased to 7.5% if needed to control 
clinical signs, but should be administered 
through a central venous catheter to prevent 
phlebitis).
• Glucagon (1–5 ng/kg/min IV as CRI) is 
gluconeogenic and may be used to effect to 
treat clinical signs associated with severe 
refractory hypoglycemia, in preparation for 
surgery.
• If exploratory laparotomy is pursued and 
complete excision of the tumor is obtained, 
long-term therapy may not be needed.
• If dietary therapy is ineffective for 
controlling hypoglycemia, glucocorticoids 
(e.g., prednisone 0.25 mg/kg PO q12h, 
increased as necessary up to 2 mg/kg PO 
q12h) may be given.
• Diazoxide (Proglycem®) stimulates hepatic 
gluconeogenesis/glycogenolysis and inhibits 
insulin secretion—dosage is 5–60 mg/kg PO 
q12h, starting at the low end and increasing 
as needed; should be used in addition to 
dietary modifications and glucocorticoids 
when they become less effective for control-
ling clinical signs.
• Streptozotocin is a nitrosourea that semi- 
selectively targets pancreatic beta -cells; may 
be given at 500 mg/m2 slow IV over 2h, after 
a 3h IV diuresis with isotonic crystalloid and 
followed by a 2h diuresis; this protocol may 
be repeated every 3 weeks until normoglyce-
mia is achieved. Streptozotocin is emetogenic 
and can be hepatotoxic and/or nephrotoxic; it 
can also cause DM secondary to cytotoxic 
effects on pancreatic beta -islet cells; is 
currently difficult to obtain.
• The synthetic somatostatin analogues 
octreotide (10–20  μg SC q8–12h) or lantreotide 
(no determined dose in veterinary species) may 
be utilized to prevent hypoglycemia in dogs 
refractory to conventional treatments.
• Anecdotal reports of the use of toceranib 
phosphate (Palladia®) exist for medical management in nonsurgical cases and/or 
postoperative treatment in patients with 
metastatic disease.
Insulin
• Dextrose boluses, when given alone, may 
precipitate further hypoglycemic crises.
• Glucocorticoids used at high dosages for 
prolonged periods can cause iatrogenic 
• Diazoxide may cause bone marrow 
suppression, gastrointestinal irritation, 
aplastic anemia, cataracts, thrombocytopenia, 
and tachycardia in humans.
• Streptozocin can cause emesis, hepatic 
failure, renal failure, DM, and pancreatitis.
• Neither diazoxide nor streptozotocin has 
been evaluated in cats.
• Glucagon is indicated for short-term 
therapy to stabilize refractory patients, but is 
not a definitive or long-term therapy.
Hydrochlorothiazide can potentiate 
diazoxide.
  FOLLOW-UP
• Teach client to monitor for return and/or 
progression of signs of hypoglycemia.
• Serum glucose determinations are important 
for monitoring for return and/or progression 
of insulinoma-associated hypo  glycemia.
• Abdominal ultrasound may be used for 
postoperative long-term monitoring.
Recurrent or progressive episodes of 
• Dogs that undergo exploratory laparotomy 
are more likely to become and remain 
euglycemic and have longer survivals than 
dogs managed by medical means.
• Even in the presence of local metastatic 
disease, any reduction of tumor burden is 
likely to improve glycemic control with 
medical therapies; the median length of 
euglycemic control after surgery is inversely 
correlated with the stage of disease and varies 
from 14 months for dogs without evidence of 
metastasis to 2–3 months for dogs with nodal 
and/or distant metastasis.
• Median survival time is inversely 
correlated with the stage of disease and 
varies from 16–19 months (range: 2–60 
months) for dogs without evidence of 
metastasis to 7–9 months in dogs with 
evidence of nodal and/or distant metasta -
sis; more recent studies have documented 
even longer median survival times of (continued)  Insulinoma

778  Blackwell’s Five-Minute Veterinary Consult  
I17–18 months for all dogs with insulinoma 
and 25–42 months for those dogs undergoing 
surgery and surgery followed by prednisone 
therapy at time of relapse, respectively.
• Cats—mean survival time about 6.5 
months; range: 0–32 months. Too few cases 
to accurately predict prognosis.
Obesity due to hyperinsulinemia.
Younger dogs have shorter survival times.SYNONYMS
• Beta-cell tumor.
• Hyperinsulinism.
• Insulin-producing pancreatic tumor.
• Insulin-secreting tumor.
• Islet or beta -cell (adeno)carcinoma.
• Islet cell tumor.
SEE ALSO
Hypoglycemia
• SPECT = single proton emission computed 
tomography.
Grant ER, Burgess KE. Canine insulinoma: 
diagnosis, treatment, & staging. Today Vet 
Pract 2016, 6(6): 60–64.Moore AS, Nelson RW, Henry CJ, et al. 
Streptozocin for treatment of pancreatic 
islet cell tumors in dogs: 17 cases (1989–
1999). J Am Vet Med Assoc 2002, 
221(6):811–818.
Polton GA, White RN, Brearley MJ, et al. 
Improved survival in a retrospective cohort 
of 28 dogs with insulinoma. J Small Anim 
Pract 2007, 48(3):151–156.
available onlineInsulinoma  (continued)

Canine and Feline, Seventh Edition  779
IInterstitial Cell Tumor, Testicle
  BASICS
OVERVIEW
Benign tumor of the testicle that arises from 
interstitial (Leydig) cells.
• 33–50% of all testicular tumors in dogs, 
but rare in cats.
• Median age, 10 years.
• Boxer, German shepherd, Afghan hound, 
Weimaraner, Shetland sheepdog, collie, and 
Maltese may be at increased risk.
SIGNS
• Usually incidental finding.
• Fertility issues in breeding dogs.
• May be associated with testosterone 
secretion and perianal gland hyperplasia or 
adenomas.
• 4–20% of dogs will have more than one 
type of testicular tumor. Up to 50% of dogs 
will have bilateral tumors; only 12% of 
contralateral tumors will be palpable.
• Generally unknown.
• Cryptorchidism—may predispose.
  DIAGNOSIS
• Sertoli cell tumor.
• Hyperadrenocorticism—with feminization.
• Hypothyroidism—with feminization.
• Usually normal, unless estrogen excess 
causes bone marrow hypoplasia (rare).
• Various cytopenias—with estrogen excess 
(rare).
• High serum estradiol concentration.
• Low serum testosterone concentration.
• Immunohistochemical evaluation with 
inhibin- α and calretinin.
IMAGING
• Testicular sonography may aid in differen-
tial diagnoses.
• Abdominal ultrasonography for retained 
testicles and to evaluate for concurrent 
malignancies.
N/A  TREATMENT
• Bilateral orchiectomy and scrotal ablation is 
the treatment of choice; exploratory laparotomy 
for retained testicles.
• Histopathologic examination of appropriate 
tissue.
• Immunohistochemistry may be necessary to 
identify cell of origin in some cases.
None, unless bone marrow hypoplasia 
induces a dangerous cytopenia.
N/A
  FOLLOW-UP
None required, unless bone marrow 
hypoplasia.
Cytopenias caused by estrogen excess.
Bilateral orchiectomy and scrotal ablation are 
often curative; cutaneous and muscle 
metastases have been reported.
• Prostate disease—with testicular tumor.
• Perianal gland hyperplasia/adenomas.
SEE ALSO
Lawrence JA, Saba C. T umors of the male 
reproductive system. In: Withrow SJ, ed., 
Small Animal Clinical Oncology. St. Louis, 
MO: Elsevier Saunders, 2013, pp. 
557–571.
Morrison WB. Cancers of the reproductive 
tract. In: Morrison WB, ed., Cancer in 
Dogs and Cats: Medical and Surgical Management. Jackson, WY: Teton 
NewMedia, 2002, pp. 555–564.
Author  Shawna L. Klahn

780  Blackwell’s Five-Minute Veterinary Consult  
IIntervertebral Disc Disease—Cats
  BASICS
OVERVIEW
• Disc extrusion or protrusion causing 
myelopathy is more common in dogs; both 
Hansen’s type I and type II disc disease, and 
acute, noncompressive nucleus pulposus 
extrusion (ANNPE) are reported in cats. 
• Type I disc disease is secondary to chondroid 
metaplasia and mineralization of the nucleus 
pulposus. •  Type II disc disease is secondary to 
fibroid degeneration and protrusion of the 
annulus fibrosus. •  With ANNPE, normal 
nucleus pulposus is extruded through a tear in 
the dorsal annulus, resulting in a concussive or 
contusive injury, with minimal to no ongoing 
compression of the spinal cord.
• For all reported cats with myelopathy 
secondary to disc disease—mean age 8.4 
years, range: 1.5–17 years. •  Cats with 
mineralized type I disc disease—mean age 7.3 
years, range: 2–13 years. •  Predominantly 
domestic breeds, several purebred (Oriental) 
breeds reported; rare exotic large cat (tiger) 
reported. •  No sex predisposition.
SIGNS
• Majority of cats have thoracolumbar or 
lumbosacral disc disease—clinical signs confined 
to pelvic limbs; cervical disc disease also described, 
in which case all four limbs may be affected; 
sacrocaudal disc disease can result in urinary 
and/or fecal retention or incontinence, lower 
lumbar pain. •  Signs frequently acute or 
peracute, but may be chronic. •  Paresis/
paralysis. •  Ataxia. •  Gait abnormality, 
lameness, reluctance to jump. •  Spinal/back 
pain. •  Urinary/fecal incontinence. 
• Abnormalities of tail carriage or tone. •  Loss 
of pain perception (if severe lesion). 
• Hypoventilation (if severe cervical lesion).
• Majority of cats reported had type I disc 
degeneration, with extrusion of mineralized 
nucleus pulposus into vertebral canal resulting 
in spinal cord trauma and compression. 
• Unlike dogs, where chondrodystrophic 
breeds (e.g., dachshunds) predisposed to type 
I disc disease and subsequent extrusion, no 
obvious risk factors apparent in cats. •  Most 
cats reported had clinically significant disc 
protrusions or extrusions between T11 and 
S1; similar to dogs, presence of the intercapital 
ligament from T1 to T10 may make disc 
protrusions in that region less likely.  DIAGNOSIS
• T rauma. •  Vascular—ischemic 
neuromyopathy (“saddle thrombus”), 
ischemic myelopathy. •  Neoplasia, especially 
lymphoma. •  Vascular—ischemia to spinal 
cord. •  Infectious—feline infectious 
peritonitis (FIP), Cryptococcus , etc.
USUALLY NORMAL.
IMAGING
• Vertebral column radiographs—narrowed 
disc space(s), mineralized discs in situ, 
mineralized disc material within vertebral 
canal or overlying intervertebral foraminae. 
• Myelography—extradural compressive 
lesion at affected disc. •  CT—extradural 
compression; mineralization of compressive 
material may be apparent. •  MRI—T2 
hyperintensity within injured cord; 
mineralized disc material appears hypointense 
on all imaging sequences; extradural 
compression may be apparent; with ANNPE, 
decreased T2 intensity of nucleus pulposus of 
likely extruded disc, hyperintensity in 
overlying spinal cord with minimal to no 
compressive epidural material.
• Cerebrospinal fluid—unremarkable or 
contaminated with blood in most cats; 
neutrophilic pleocytosis noted in three cats. 
• Histopathology of material removed at 
surgery—consistent with degenerative disc 
material (type I or II).
  TREATMENT
• Surgical spinal cord decompression likely 
most effective treatment for compressive disc 
disease; cats with noncompressive disc 
extrusions had successful outcomes with 
physical rehabilitation alone. •  Risks of spinal 
surgery should be discussed with owner—
hemorrhage, iatrogenic injury to spinal cord, 
instability. •  Hemilaminectomy, ventral slot, 
lateral corpectomy, and lumbosacral dorsal 
laminectomy surgeries are described in the 
cat. •  Postoperative care—good recumbent 
patient care, pain management, bladder 
management if incontinent cat (indwelling 
urinary catheter or manual expression), and 
appropriate physical therapy. •  Fenestration of adjacent mineralized discs should be 
considered to avoid recurrence. •  Medical 
management (cage rest, pain management) 
may be considered in ambulatory cats, but 
more aggressive diagnostics and treatment 
should be considered in nonambulatory cats 
and those with progressive neurologic signs.
• Pain management, preferably opiates, if cat 
tolerates them. •  Efficacy of corticosteroids 
in feline disc disease has not been evaluated.
  FOLLOW-UP
• Repeat neurologic examinations (at least 
1–2 times/day) during hospitalization to 
monitor postoperative and medically 
managed patients for improvement or decline 
in neurologic status. •  Strict cage rest for 
medically managed and postoperative patients 
for 4–6 weeks, then gradual increase in 
activity and physical therapy, as needed. 
• Unknown whether long-term activity 
restriction beneficial. •  Because disc disease 
uncommon in cats, possible recurrence rate 
unknown, but in one cat that recovered well 
after hemilaminectomy, additional mineralized 
disc extrusion caused paraplegia and 
necessitated second surgery (unpublished 
data). •  A few cats had persistent urinary 
retention in spite of good recovery of 
ambulation, requiring routine bladder 
expression by owner. •  Majority of cats 
managed surgically (even two without pain 
perception) had good to excellent outcome.
• ANNPE = acute, noncompressive nucleus 
Rayward RM. Feline intervertebral disc 
disease: a review of the literature. Vet Comp 
Orthop T raumatol 2002, 15:137–144.
Author  Marguerite F . Knipe

Canine and Feline, Seventh Edition  781
IIntervertebral Disc Disease, Cervical
  BASICS
Degeneration of the cervical intervertebral 
discs that may result in protrusion or 
extrusion of disc material into the spinal 
canal. The protruded or extruded disc 
material causes spinal cord compression 
(myelopathy) and/or nerve root compression 
(radiculopathy), as well as concussive spinal 
cord injury in varying degrees.
• T raditionally classified as acute disc 
herniation (Hansen type I disc) or chronic 
disc protrusion (Hansen type II disc); other 
types include extrusion of apparently healthy, 
hydrated nucleus pulposus with or without 
spinal cord compression, the latter termed 
acute noncompressive nucleus pulposus 
extrusion (ANNPE).
• Hansen type I—degeneration of the 
nucleus pulposus and acute rupture of the 
annulus fibrosus with extrusion of the nucleus 
pulposus into the spinal canal.
• Hansen type II—fibrinoid degeneration 
and protrusion of the dorsal annulus fibrosus 
into the vertebral canal (can involve a 
dynamic component).
• Disc extrusion or protrusion into the spinal 
canal causes focal compression of the spinal 
cord (myelopathy) and/or focal compression 
of a nerve root (radiculopathy) in addition to 
a variable degree of contusion injury; ANNPE 
primarily results in a contusion injury.
• Consequences of spinal cord compression 
are ischemia and demyelination.
• Consequences of spinal cord contusion 
include axonal and vascular injury as well as 
secondary cellular injury.
• Disc extrusion may be secondary to trauma, 
but this rarely occurs aside from those 
patients with hydrated disc herniations.
• Surgical fusion of cervical vertebrae may 
alter the biomechanics of adjacent vertebral 
bodies and therefore predispose discs to 
protrusion or extrusion; this is termed the 
domino effect.
Nervous system—either focal myelopathy or 
focal radiculopathy.
GENETICS
• Not known.
• Chondrodystrophic breeds (e.g., dachshund) 
are most commonly affected with Hansen type 
I disc extrusion.
• Large-breed dogs are most commonly 
affected with Hansen type II disc extrusion.
Species
Dogs, rarely cats.Breed Predisposition
• Hansen type I—dachshund, poodle, beagle, 
cocker spaniel, French bulldog, shih tzu; 
chondrodystrophic breeds.
• Hansen type II—Doberman pinscher, 
• Hansen type I—3–6 years of age.
• Hansen type II—8–10 years of age.
None recognized.
SIGNS
• Severity of clinical signs and spinal cord 
injury is dependent on several factors, 
including the rate and volume of disc 
protrusion or extrusion, spinal cord diameter 
relative to vertebral canal diameter, and the 
velocity of disc material that is extruded.
• Herniation in the cervical region can result 
in fewer neurologic deficits compared to 
similar lesions in the thoracolumbar region, 
because the spinal canal area is greater and 
can accommodate more disc material before 
spinal cord compression.
• Neck pain—most common owner 
• Stiff, stilted gait, lameness, or reluctance to 
move the head and neck.
• Lowered head stance and muscle spasms of 
the head, neck, and shoulder.
• Inability to rise or falling forward frequently.
• Neck pain—elicited upon slow manipulation 
of the neck or by deep palpation of the cervical 
muscles.
• Apparent forelimb lameness or nerve root 
signature (e.g., a thoracic limb that knuckles, 
appears lame, or is held in partial flexion).
• Paresis with or without general proprio -
ceptive deficits involving one or both thoracic 
and pelvic limbs may be present.
• Pelvic limb paresis may be more severe than 
thoracic limb paresis.
• Pelvic limb spinal reflexes may be normal to 
exaggerated.
• Thoracic limb spinal reflexes may be 
normal to exaggerated when lesions are 
located in the C1–C6 spinal cord segment, 
and may be normal to decreased when the 
C6–T2 spinal cord segment is affected, 
although this finding is not reliable in some 
patients.
• Severity of clinical signs and degree of 
compression are not always correlated.
• Bladder function may be upper motor 
neuron in nature or normal.
CAUSES
• Degeneration of the intervertebral disc 
material and subsequent herniation or 
protrusion.
• T rauma may lead to extrusion of healthy 
material or otherwise degenerative material.RISK FACTORS
Obesity and repeated traumatic events in 
those breeds predisposed to intervertebral disc 
disease.
  DIAGNOSIS
• Atlantoaxial instability.
• Spinal fracture/luxation.
• Fibrocartilaginous embolism.
• Systemic illness—hypoadrenocorticism, 
• Spondylomyelopathy.
Often performed in anticipation of 
medication administration, general 
anesthesia, and/or surgery.
• Cerebrospinal fluid (CSF) analysis—
performed under general anesthesia (prior to 
myelography if performed).
• CSF analysis reveals nonspecific changes 
such as mild to moderate elevation in protein 
levels and mild to moderate pleocytosis, 
which is more pronounced in Hansen type I 
disc extrusion.
• Electromyography may be useful if the 
underlying cause is associated with denervation.
IMAGING
• MRI and CT are most sensitive for diagnosis 
of cervical intervertebral disc disease and 
intervertebral disc herniation (IVDH) as well 
as for surgical planning.
• MRI is the best available method for early 
recognition of intervertebral disc degeneration 
(IVDD) in dogs and is capable of the most 
complete evaluation of the spinal cord 
• CT is also useful in diagnosis of spinal cord 
compression, especially by degenerative disc 
material; the spinal cord parenchyma is not as 
well assessed with this modality compared 
with MRI.
Cervical Spinal Radiography
• Well-positioned lateral and ventrodorsal 
survey radiographs of the cervical spine aid in 
excluding other differentials (i.e., discospondy -
litis, fracture/luxation, atlantoaxial instability, 
or lytic vertebrae suggestive of a bone tumor), 
but are not reliable for many patients with 
IVDH.
• Classic findings include narrowed 
intervertebral disc space or disc space 
wedging, collapse of the articular facets, or 
calcified disc material present in the

782  Blackwell’s Five-Minute Veterinary Consult  
Iintervertebral foramen or in the spinal canal, 
although many of these findings can be seen 
without clinical signs, especially in over -
represented breeds.
• Hansen type II disc disease may be 
associated with spondylosis deformans.
• Survey cervical radiographs may be 
misleading; therefore, myelography is more 
sensitive compared to survey radiographs, 
although cross-sectional imaging has replaced 
this modality in most practices.
• Lateral radiographs reveal dorsal deviation of the 
ventral contrast column over the intervertebral 
disc space consistent with extradural compression; 
intraforaminal or dorsolateral disc herniation is 
best seen on an oblique views.
• Acute cases with spinal cord swelling can 
cause blockage of contrast material and prevent 
it from flowing past the obstruction, limiting 
the diagnostic capabilities of the image.
CSF analysis.
Gross Findings
• Hansen type I disc—white extruded disc 
material that has a granular consistency and is 
usually easily removed from the spinal canal.
• Hansen type II disc—firm protrusion of 
the dorsal annulus fibrosus that is adherent to 
the floor of the spinal canal and to the dura of 
the spinal cord; type II discs are much more 
difficult to remove from the spinal canal.
• Spinal cord—in acute disc extrusion the 
spinal cord may appear bruised or swollen or 
may appear grossly normal; in chronic disc 
protrusion, the spinal cord may appear to be 
atrophied but is often normal in appearance.
Histopathologic Findings
• Hansen type I disc—shifting concentration 
of glycosaminoglycans, loss of water and 
proteoglycan content, and increased collagen 
content; the disc becomes more cartilaginous 
and undergoes dystrophic calcification.
• Hansen type II disc—a gradual fibroid 
metaplasia leaves the disc with increased 
glycosaminoglycan levels and lower collagen 
content; the nucleus does not undergo 
cartilaginous metaplasia.
• Spinal cord—dependent on the severity of the 
disease and type of disc disease; Hansen type II: 
demyelination and gliosis are seen; Hansen type 
I: hemorrhage and edema can be seen; with 
severe disease, myelomalacia can be observed.
  TREATMENT
• Conservative or surgical management 
dependent on patient’s history and presenting 
neurologic status.• In general, conservative management can be 
considered with a gradual onset of clinical 
signs or clinical signs that are limited to 
hyperpathia or mild ataxia.
• Surgical management is often indicated in 
patients with repeated episodes of neck pain, 
severe neck pain and neurologic deficits, or a 
lack of response to conservative management.
• Patients with hydrated intervertebral disc 
herniations may perform similarly with 
conservative and surgical treatment.
• ANNPE is treated conservatively as there is 
no compression to address surgically.
• Level of nursing care needed depends on the 
severity of the injury; if unable to be cared for at 
home, patients should be monitored as inpatients.
• Minimal manipulation of the head and 
neck to avoid worsening discomfort.
• Urination—monitor patients for complete 
emptying of the bladder; patients may need to 
have bladder manually expressed or intermittent 
bladder catheterization; in some cases, indwelling 
urinary catheter may need to be placed.
• Defecation—patients typically defecate 
normally, although frequent cleaning and 
management of any soft stool are important.
• Recumbent patients—should be kept on a 
well-padded mat and turned frequently (often 
every 4 hours); should be checked for pressure 
sores over bony prominences; should be 
diligently cleaned and kept dry.
• Physical therapy—passive range of motion 
of all joints should be performed as often as 
possible to prevent severe muscle atrophy, 
especially in patients with minimal voluntary 
motor ability; hydrotherapy can be considered 
in tetraparetic patients as well.
ACTIVITY
• Activity should be very limited; no running 
or jumping, and confined to a crate-sized 
space; when patients are being walked, a 
harness should be used instead of a collar.
• With conservative or postoperative 
management, patients should be strictly 
confined to cage rest for 4 weeks, followed by 
a gradual return to normal activity over the 
course of another 4 weeks.
DIET
For obese patients, a decrease in caloric intake 
should be instituted.
• Appropriate expectations for clinical 
improvement or signs of worsening should be 
discussed.
• Confinement is very important for recovery.
• Weight loss if the animal is obese.
• The goal of surgery is to remove disc 
material from the spinal canal and therefore 
decompress the spinal cord and/or nerve root.
• Surgery usually provides rapid pain relief 
and significantly improved motor function.• A ventral cervical slot is the most common 
surgical approach for the removal of disc 
material; disc material that has extruded 
dorsolaterally into the intervertebral foramen 
or dorsally is removed via a lateral approach 
or through a dorsal laminectomy.
• Fenestration alone for dogs with neck pain 
usually does not resolve clinical signs and is 
no longer recommended.
• Anti-inflammatory therapy (low-dose 
glucocorticoid or nonsteroidal anti-
inflammatory drugs [NSAIDs]) is often 
beneficial in order to decrease the pain in 
animals that are being treated conservatively 
as well as those recovering from surgery; use 
of high-dose glucocorticoids is not well 
supported by the literature and is generally 
• Analgesic medications such as gabapentin 
and muscle relaxants such as methocarbamol 
can also be used in conjunction with anti- 
inflammatories to improve pain control in 
both conservative as well as surgical 
Systemic status should be considered when 
choosing medications.
Anti-inflammatories or analgesic medications 
given to animals without simultaneous strict 
cage confinement could exacerbate disc 
extrusion by encouraging activity.
Using glucocorticoids with NSAIDs can 
cause severe gastrointestinal irritation and 
possibly intestinal perforation.
  FOLLOW-UP
• Weekly evaluations should be performed 
until resolution of clinical signs or until 
clinical progress plateaus.
• All patients should be fitted with a harness, 
and neck collars should be avoided.
• Inherent in particular breeds.
• Keeping patients at an ideal weight may 
help.
• Complications are uncommon.
• Conservative management—continued 
neck pain, deteriorating motor status.
• Surgical management—hemorrhage, 
infection, neurologic deterioration, Intervertebral Disc Disease, Cervical  (continued)

Canine and Feline, Seventh Edition  783
Irespiratory compromise, subluxation/
luxation of vertebral bodies, collapse of 
intervertebral disc space, and foraminal 
collapse.
• Prognosis for patients treated surgically or 
conservatively depends on neurologic signs at 
the time of presentation; lack of nociception 
leads to a poor prognosis for recovery of 
function long term (<50%) and duration of 
clinical signs beyond days likely worsens the 
• Prognosis is generally favorable for most 
patients; surgical treatment often leads to 
rapid improvement in pain control, especially 
in patients undergoing a ventral slot 
• Some patients treated conservatively have 
recurrence of disease or deterioration and may 
require surgical intervention.• Patients who experience IVDH may be 
predisposed to IVDH at other sites in the future 
due to the underlying pathology (IVDD).
Animals predisposed to cervical disc disease 
are also the same breeds that are predisposed 
to thoracolumbar disc disease.
SEE ALSO
Intervertebral Disc Disease, Thoracolumbar.
• IVDD = intervertebral disc degeneration.
• IVDH = intervertebral disc herniation.• NSAID = nonsteroidal anti-inflammatory 
drug.
Jeffery ND, Levine JM, Olby NJ, Stein VM. 
Intervertebral disc degeneration in dogs: 
consequences, diagnosis, treatment and 
future directions. J Vet Intern Med 2013, 
27(6):1318–1333.
Lorenz MD, Coates J, Kent M. Handbook of 
Veterinary Neurology, 5th ed. St. Louis, 
MO: Saunders, 2011.
Author  Lindsay Boozer
Otto I. Lanz
available online(continued)  Intervertebral Disc Disease, Cervical

784  Blackwell’s Five-Minute Veterinary Consult  
IIntervertebral Disc Disease, Thoracolumbar
  BASICS
Intervertebral disc disease (IVDD) is an acute 
traumatic or chronic degenerative condition 
that causes loss of normal neurologic function 
to the pelvic limbs, bladder, and anal 
sphincter. Intervertebral discs chronically 
degenerate by loss of water, cellular necrosis, 
and dystrophic calcification. In the chronic 
condition, biomechanical properties of the 
disc deteriorate, and subsequently protrusion 
(Hansen type II) or extrusion (Hansen type I) 
of disc material occurs.
• Intervertebral disc degeneration is 
initiated by one or more factors including 
trauma, chronic overload, decreased spinal 
mobility, age-related deterioration in 
collagen and cartilage, and hypermobility. 
• Hansen type I refers to acute extrusion 
of nucleus pulposus through the annulus 
fibrosis into the vertebral canal; Hansen 
type I lesions typically occur in chondro -
dystrophic dogs, but may occur in larger 
nonchondrodystrophic dogs as well; onset 
of neurologic signs is usually acute and 
often severe; acute disc extrusion results in 
extruded material causing direct trauma to 
the spinal cord and residual disc mass 
leading to extradural spinal cord compres -
sion; trauma and spinal cord compression 
results in ischemia and spinal cord changes 
that vary from mild demyelination to 
necrosis of both gray and white matter; 
events at the cellular level include release 
of vasoactive substances, increased 
intracellular calcium, and increased free 
radical formation and lipid peroxides. 
• Hansen type II lesions involve gradual 
protrusion (bulging) of the dorsal annular 
fibers into the vertebral canal associated 
with fibroid degeneration of the disc; 
Hansen type II lesions typically occur in 
nonchondrodystrophic dogs; the most 
common case presentation is of gradual 
onset of neurologic dysfunction and slow 
progression. •  Hansen type III injuries 
occur when the nucleus pulposus herniates 
with such force as to enter the spinal cord 
by penetration of the dura; Hansen type 
III injuries are rare, but carry a poor 
prognosis because they are commonly 
associated with subsequent myelomalacia 
and loss of deep pain response.• Affected 
animals exhibit pain due to dural irrita -
tion, nerve root impingement, or possibly 
discogenic (annular pain receptors) in 
origin. •  Disc herniation is rare between 
T3 and T10 owing to the barrier of the 
intercapital ligament between dorsal 
annulus and spinal cord.SYSTEMS AFFECTED
• Nervous. •  Neuromuscular. •  Renal/
urologic (loss of voluntary urethral sphincter 
control). •  Digestive (loss of voluntary anal 
sphincter control). •  Musculoskeletal (muscle 
atrophy in chronic disease).
GENETICS
Early studies suggest a polygenetic model 
with no dominance or sex linkage.
• Most common neurologic dysfunction in 
small animals; affects 2% of the canine 
population. •  Occurs less commonly in cats, 
but the exact incidence is unknown, and the 
disease is likely underdiagnosed or reported 
due to lack of suspicion as a differential 
diagnosis. •  In specific breeds, such as 
dachshunds, affected prevalence as high as 
20% has been reported. •  Thoracolumbar 
disc disease comprises 85% of all disc 
herniations; 70% occur from T11 to L3.
Species
Dog and occasionally cat.
• Type I—dachshund; shih tzu, Lhaso apso; 
Pekingese, cocker spaniel, Welsh corgi; toy 
and miniature poodle. •  Type II—large 
breeds, but may occur in any breed. •  Type 
III—active agility, racing, or working breeds; 
greyhound; border collie; Australian 
shepherd.
• Type I—3–6 years of age. •  Type II—8–10 
years of age; cats: mean age of 10 years. 
• Type III—any age; occurs during exertion 
or trauma.
SIGNS
The severity of clinical signs depends on the 
type of herniation, velocity of disc contact 
with the spinal cord, amount and duration of 
cord compression, location (upper motor 
neuron [UMN] or lower motor neuron 
[LMN]), and regional spinal canal/spinal cord 
diameter ratio (cervical vs. thoracolumbar).
• Onset may be peracute or acute in 
chondrodystrophoid dogs (type I disease) and 
may occur during vigorous activity. •  Larger 
dogs or smaller dogs with type II disease have 
a more insidious onset and tend to worsen 
with time. •  Dogs with type III disease have a 
history of active exertion followed by sudden 
loss of function, or of severe traumatic origin 
such as vehicular trauma or racing injury.
• Thoracolumbar pain is a common finding 
in dogs; reluctant to ambulate and hunched 
posture; careful palpation of spinous processes and epaxial musculature produces 
distinct localized pain; often some degree of 
paraparesis with decreased or absent 
proprioception or decreased motor ability in 
the pelvic limbs. •  Myotactic spinal reflexes 
in the pelvic limbs are exaggerated (hyper -
reflexive) when the lesion is between T3 and 
L3; reflexes are decreased (hyporeflexive) 
when lesion is caudal to L3. •  Superficial 
and deep pain perception may be decreased 
or absent in the pelvic limbs. •  Presence of 
deep pain sensation is the single most reliable 
prognostic factor for return to acceptable 
function; pain perception should be 
conscious in nature and not confused with a 
withdrawal reflex (local spinal reflex); in 
animals with diminished conscious deep pain 
response, observation of mydriasis or 
tachycardia may be useful in confirming the 
presence of deep pain. •  Forelimb function is 
normal with thoracolumbar disc rupture; 
occasionally Schiff–Sherrington phenomena 
may cause increased muscle tone in the 
forelimbs, but this clinical sign is location 
related only and does not indicate a poor 
prognosis. •  Urinary incontinence or 
retention is common when the lesion affects 
motor function. •  Pain is less obvious in 
cats; the site of herniation is often lumbar.
CAUSES
• Chondroid or fibroid degeneration of the 
thoracolumbar intervertebral discs. •  Acute 
trauma that overloads the capacity of the 
intervertebral disc to absorb force and 
ruptures the dorsal annulus. •  15% of 
animals with spinal fractures have been 
reported to have disc extrusions in addition to 
the fracture/luxation.
• Type I disease most often affects chondro -
dystrophic breeds. •  Racing and breeds used 
for agility competition are at risk for Type III 
disk disease.
  DIAGNOSIS
• Type I—trauma causing fracture/luxation, 
neoplasia, discospondylitis, fibrocartilaginous 
embolism; differentiated by history, survey 
radiography, myelography, CT, or MRI. 
• Type II—degenerative myelopathy, spinal 
neoplasia, discospondylitis, orthopedic 
disease; differentiated by history, radiographic 
modalities, and careful orthopedic and 
neurologic examination. •  Type III—trauma 
causing spinal fracture or subluxation/
luxation of vertebrae in the thoracolumbar 
region, fibrocartilaginous embolism, or Type I 
disk disease; differentiated by survey radio -
graphy, myelography, CT, or MRI.

Canine and Feline, Seventh Edition  785
ICBC/BIOCHEMISTRY/URINALYSIS
• Elevation of liver enzymes is common if the 
patient has received previous corticosteroids 
for pain or neurologic disease. •  Urine 
retention/incontinence increases risk of 
urinary tract infection characterized by 
leukocytes, protein, and bacteriuria on 
Cerebrospinal fluid (CSF) analysis performed 
routinely in conjunction with myelography if 
there is high suspicion of another disease 
process; may be normal, but more typically 
shows mild to moderate increase in protein 
with or without pleocytosis when IVDD 
occurs.
IMAGING
• Thoracolumbar spinal radiography with the 
patient anesthetized; unanesthetized radiographs 
can be used to rule out neoplasia and other 
processes, but can be misleading for thora -
columbar disc disease. •  Survey radiographs 
rule out some other disease processes. 
• Diagnostic radiographs taken under general 
anesthesia may reveal a narrowed or wedged 
disc space, collapsed articular facet space, and 
small intervertebral foramen with increased or 
mineralized density within the spinal canal. 
• Accuracy and sensitivity of survey radio -
graphs for determining a specific site of disc 
herniation are low; in conjunction with careful 
neurologic examination, the exact location can 
often be narrowed down to a small vertebral 
area, but the extent of herniation and pressure 
on the meninges from herniation of disc 
material may extend over more than one space.
• MRI is now considered the diagnostic 
mode of choice when available due to the 
noninvasive nature and superior informa -
tion regarding location and extent of 
disease; presence of a hyperintense spinal 
cord lesion as long as the body of L2 on a 
T2-weighted image in deep-pain-negative 
dogs is associated with a poorer prognosis. 
• CT with or without contrast is often 
diagnostic in chondrodystrophic dogs; 
dystrophic calcification of extruded 
material is easily visualized and laterali -
zation can be easily determined; contrast 
enhancement can different disc disease 
from neoplastic or granulomatous pro -
cesses. •  Myelography performed with 
iohexol was previously the method of 
choice and is still indicated when CT or 
MRI is not available; the contrast agent is 
usually introduced at L5–L6; positive 
diagnosis is an extradural mass lesion 
causing spinal cord compression adjacent to 
the affected disc; spinal cord swelling may 
be evidenced by thinning of contrast 
columns over several intervertebral spaces. 
• Lateralization is more consistent when determined from both oblique and 
dorsoventral myelogram views. •  CSF 
analysis is an important addition when 
alternative causes of neuropathy are likely 
differential diagnoses or when imaging 
findings are equivocal or nondiagnostic.
Gross
• Extruded disc material (type I disease)—
white to yellow and “toothpaste” consistency 
seen on laminectomy; if chronic, may be 
hardened and adhered to surrounding 
structures; extradural hemorrhage is usually 
present and mixed with extruded disc 
material; the ventral sinus may be ruptured 
and actively bleeding; subdural hemorrhage 
may be visible. •  Protruded disc material 
(type II disease)—usually firm, grayish-white, 
and may be adherent to surrounding 
structures; compression of the spinal cord is 
apparent, but usually without evidence of 
recent hemorrhage or trauma visible. 
• Extradural or intradural hemorrhage 
without or with minimal extruded disc 
material (type III disease); the dural 
membrane may be penetrated and extruded 
material may be present within the spinal 
cord parenchyma; myelomalacia may be 
detectable as loss of dural and parenchymal 
integrity at the affected site. •  Spinal cord 
may appear normal or be swollen and 
discolored in acute severe disease.
• Degenerated discs have decreased amounts 
of proteoglycans, glycosaminoglycans, and 
water; discs may become mineralized or 
cartilaginous. •  Spinal cord lesion depends 
upon type and severity of disc extrusion or 
protrusion; acute, severe disease may cause 
hemorrhage, edema, tissue necrosis; chronic 
disease demyelination of white and in some 
cases gray matter.
  TREATMENT
Guidelines for Therapy Based 
on Classification of Clinical Condition
• Class 1—back pain only, first episode. 
• Class 2—recurrent back pain, ataxia, mild 
paraparesis, motor ability good. •  Class 
3—severe paraparesis, proprioceptive deficits, 
motor ability affected but still present; 
voluntary control of urination may be 
diminished; bladder many be easy to 
manually express or difficult due to detrusor 
dysfunction. •  Class 4A—complete paralysis 
(no motor ability) with deep pain perception 
present; voluntary control of urination and 
defecation absent, bladder usually easy to express manually. •  Class 4B—complete 
paralysis, no deep pain perception present.
Treatment Recommendations Based 
• Class 1—treated medically unless pain 
persists. •  Class 2—treated medically initially 
with serial neurologic exam; surgery is 
performed if patient remains static or 
condition declines. •  Classes 3 and 4A—
immediate surgical decompression 
recommended; prognosis good. •  Class 
4B—surgical decompression and fair 
prognosis if within the first 12–48 hours of 
occurrence or for slower onset of clinical signs 
(clinical signs progressive over 12 hours); 
poor prognosis if deep pain perception has 
been absent for >48 hours or if the clinical 
signs progressed rapidly (<6 hours) from 
normal to loss of deep pain. •  Serial 
neurologic examination important for all 
• Absolute restricted confinement for 2–4 
weeks or until ambulatory. •  Minimize spinal 
manipulation and support spine when 
handling patient. •  Ensure ability to urinate 
or consider bladder expression, intermittent 
catheterization, or indwelling urinary catheter 
for patients in classes 3–4B. •  Recumbent 
patients should be kept clean on padded 
bedding placed on elevated cage racks and 
turned frequently to prevent formation of 
decubital ulcers. •  Manual evacuation of the 
bowel or enemas may be necessary to 
promote defecation. •  Physical therapy with 
passive manipulation of pelvic limbs begun 
early followed by more intense therapy 
(hydrotherapy) for animals with neurologic 
deficits but regaining motor function; 
rehabilitation protocols are not contraindi-
cated, but recent research suggests that they 
may not be beneficial in improving the speed 
of return to function. •  Carts useful in many 
patients in promoting return to function; 
patient tolerance is limiting factor.
ACTIVITY
• Restricted movement most important part 
of medical management. •  Cage rest in 
hospital or enforced cage rest as an outpatient 
for 2–4 weeks for class 1 patients or 
postoperative animals.
DIET
Weight reduction if patient is obese.
• Some degree of restricted activity may be 
important for the remainder of the animal’s life 
since it has disc disease. •  Most animals in 
classes 1–4A have a good to excellent prognosis 
for return to function, i.e., ambulation with 
bowel and bladder continence; patients in class

ACTIVITY
DIET
bowel and bladder continence; patients in class 
4B have a poorer but not hopeless prognosis; (continued)  Intervertebral Disc Disease, Thoracolumbar

786  Blackwell’s Five-Minute Veterinary Consult  
Ipercentages vary, but up to approximately 50% 
may regain deep pain and some function, 
especially if appropriate surgical decompression 
occurs early in the disease process.
• Surgery strongly indicated for animals in 
classes 3 and 4, also within the first 12–48 
hours for class 4B dogs; also indicated for static 
or worsening class 1 and 2 dogs. •  Primary 
surgical goal is to relieve spinal cord compres -
sion by disc mass removal via hemilaminec -
tomy, dorsal laminectomy, or pediculectomy; 
disc fenestration alone is not effective for 
treating acute disc extrusions, but is frequently 
recommended as an adjunct to decompression 
at the primary site. •  Hemilaminectomy on the 
side of predominant disc extrusion is the 
surgical procedure of choice for most thora -
columbar discs; studies indicate improved 
return to function, minimized spinal destabili -
zation, and decreased formation of compressive 
laminectomy scars in the long-term postopera -
tive period. •  Foramenotomy and pediculec -
tomy are similar to hemilaminectomy and may 
allow a more limited approach and decreased 
cord manipulation. •  Dorsal laminectomy is 
the procedure of choice for disc herniation in 
the region of the lumbosacral plexus or where 
extensive examination of the spinal cord is 
necessary. •  Recurrence of clinical signs in 
animals in the immediate postoperative period 
may be due to further extrusion of disc from 
the original site if fenestration is not adjunc -
tively performed at the site of disc disease 
during hemilaminectomy or dorsal laminec -
tomy; later recurrence of clinical signs after 
recovery is usually due to protrusion/extrusion 
at adjacent sites; several studies document 
approximately 8% long-term recurrence of 
clinical signs in dogs after initial hemilaminec -
tomy and active site fenestration due to 
protrusion/extrusion at other sites. •  Controversy 
remains over the efficacy of multiple site 
prophylactic disc fenestrations performed 
during the decompressive surgery, because 
evidence that fenestration prevents recurrence 
of clinical signs is not definitive and fenestration 
causes osteoarthritis to form at the intervertebral 
space of each site of fenestration, leading to 
potential chronic patient discomfort and pain.
(NSAIDs) or narcotics may be used as 
analgesics in class 1 cases to alleviate 
patient discomfort during recovery; use of 
analgesics is not a substitute for the cage 
rest period required of all patients. 
• Narcotic analgesics may be necessary 
postoperatively; hydromorphone (0.05–0.2 mg/kg IV/IM/SC q4h) or similar 
narcotic injectable used at appropriate 
doses are the treatment of choice in the 
immediate postoperative period; oral 
narcotics such as codeine (1–2 mg/kg PO 
q8h) or tramadol (5–8 mg/kg PO q8h) are 
useful to alleviate patient discomfort within 
the first week after decompression; trans -
dermal lidocaine or fentanyl may be useful 
modes of analgesic administration in some 
animals, particularly those intractable to 
frequent dosing of injectable or oral agents. 
• Gabapentin (5–10 mg/kg PO q12h), an 
NMDA receptor antagonist in dogs with 
chronic pain sensitization, is not an 
appropriate analgesic used alone in the 
immediate postoperative period. 
• Methocarbamol (25–45 mg/kg q8h) may 
be useful in cases where muscle spasm is 
contributing to pain; more applicable with 
cervical disease. •  Bethanechol (5–15 mg/
dog PO) and phenoxybenzamine (0.25 mg/
kg PO q8–12h) or prazosin (1 mg/15 kg 
PO q8–12h) are variably helpful in 
managing bladder dysfunction associated 
with spinal cord lesion. •  Previous 
indications for methylprednisolone sodium 
succinate for treatment of acute pain are 
now controversial for efficacy; the high 
potential for side effects may outweigh the 
small gains from the drug. 
• Corticosteroids are no longer commonly 
recommended in the treatment of acute 
intervertebral disc disease due to lack of 
demonstrated clinical efficacy.
• Glucocorticoid use is discouraged in cases 
of IVDD where drug side effects such as 
gastrointestinal hemorrhage and intestinal 
perforation often far outweigh benefits; 
potent glucocorticoids such as dexamethasone 
should never be used. •  Glucocorticoids are 
contraindicated within 48 hours of using an 
NSAID in dogs. •  Use of glucocorticoids 
without cage confinement may decrease pain, 
thereby encouraging excessive activity and 
leading to further disc herniation and 
deterioration of clinical condition.
Alternative Therapies
• Acupuncture use has been described, but 
consistent efficacy has not been demonstrated. 
• Chiropractic therapy has no proven 
benefits for IVDD and may potentially be 
harmful to the animal. •  Percutaneous 
therapeutic lasers do not reach the site of 
inflammation and are not efficacious; one 
recent study did demonstrate slightly more 
rapid recovery from IVDD if laser therapy 
regimens occurred as an adjunct to surgical 
decompression procedures. •  Discolysis by 
enzymatic injection or laser ablation has been 
described but is not proven therapy in dogs.  FOLLOW-UP
• Patients treated medically should be 
reevaluated two to three times daily for 
worsening neurologic signs for the first 48 
hours after onset. •  If stable, reevaluate daily, 
then weekly, until clinical signs have resolved. 
• Patients treated surgically are evaluated 
twice daily until improvement is noted; 
urinary bladder function or awaiting 
development of an autonomic bladder are the 
limiting factors for hospitalization.
• Recurrence of signs associated with disc 
herniation at original or at new site. 
• Deterioration of clinical signs with or 
without surgery; continued inflammatory 
processes initiated by the initial extrusion 
may result in myelomalacia or diminished 
function. •  Rarely, development of ascending 
or descending myelomalacia; occurs in class 
4A or 4B dogs 3–5 days following injury and 
is characterized by variable and progressive 
neurologic deterioration, possible fever, 
possible dyspnea, and extreme pain, with the 
cranial movement of the inflammation; 
careful monitoring of the anatomic position 
of detection of the panniculus reflex is 
recommended; cranial movement of the reflex 
can indicate ascending myelomalacia and 
provide early warning of a grave condition; 
such animals are often euthanized when 
• Overall prognosis for dogs in classes 1–4A 
good to excellent (85–95%); those treated 
conservatively may experience recurrence of 
clinical signs. •  Recurrence rates of dogs 
without fenestration at the time of laminectomy 
range from 5–30%. •  Dogs in class 4B have a 
variable (10–75%) chance of recovery; overall a 
guarded but seemingly favorable prognosis if 
surgery is performed within 48 hours and the 
animal is allowed sufficient time to recover. 
• Dogs with type III disc extrusions often 
exhibit severe initial clinical signs and carry a 
grave prognosis for full recovery.
• IVDD = intervertebral disc disease.
drug.

drug. 
• UMN = upper motor neuron.Intervertebral Disc Disease, Thoracolumbar  (continued)

Canine and Feline, Seventh Edition  787
I Suggested Reading
Dewey CW. Surgery of the thoracolumbar 
spine. In: Fossum TW, ed., Small Animal 
Surgery, 4th ed. St. Louis, MO: Elsevier 
Mosby, 2013, pp. 1508–1528.
Kerwin SC, Levine JM, Mankin JM. 
Thoracolumbar vertebral column. In: Johnston SA, Toias KM, eds., Veterinary 
Surgery: Small Animal, 2nd ed. St. Louis, 
MO: Elsevier, 2018, pp. 485–513.
Zidan N, Sims C, Fenn J, et al. A 
randomized, blinded, prospective clinical 
trial of postoperative rehabilitation in dogs 
after surgical decompression of acute 
thoracolumbar intervertebral disc herniation. J Vet Int Med 2018, 
32:1133–1144.
available online(continued)  Intervertebral Disc Disease, Thoracolumbar

788  Blackwell’s Five-Minute Veterinary Consult  
IIntussusception
  BASICS
• Invagination of one gastrointestinal (GI) 
segment into the lumen of the adjacent 
segment. •  Intussusceptions are classified 
according to their localization within the GI 
tract—ileocolic and jejunojejunal intussus­
ceptions are the most common; other types 
include gastroesophageal, duodenojejunal, 
and cecocolic.
• The mechanism is unknown—GI irritation 
and hypermotility may cause the orad 
segment to invaginate into the aborad 
segment; uncoupling of coordinated 
peristaltic rhythm may be a contributing 
factor. •  Intussusception often leads to a 
partial or complete mechanical obstruction of 
the GI tract. •  Compromise of venous and 
lymphatic drainage of the affected bowel leads 
to marked edema and intramural hemorrhage, 
and, if left untreated, loss of segmental 
arterial supply and necrosis; full ­thickness 
compromise of the integrity of the bowel may 
occur leading to septic peritonitis. •  The 
segment entrapped within the lumen is the 
intussusceptum; the engulfing segment is the 
intussuscipiens.
• GI—partial or complete mechanical 
obstruction, bowel wall necrosis, 
hematochezia, melena, hypermotility 
followed by ileus, vomiting, and diarrhea. 
• Cardiovascular—distributive and 
hypovolemic shock (vomiting and diarrhea, 
intraluminal hemorrhage, peritonitis).
GENETICS
N/A
Uncommon
N/A
Species
Dog > cat.
• German shepherd—gastroesophageal 
intussusceptions (60% of reported cases) and 
other types of intussusceptions. •  Siamese 
cats are overrepresented.
• Most commonly younger animals. •  Older 
affected animals should be evaluated for 
underlying disease such as chronic enteropathy 
and intestinal neoplasia.
NoneSIGNS
• Clinical signs depend on the inciting cause, 
location and type of intussusception, complete­
ness of obstruction, degree of bowel wall 
compromise and presence of peritonitis. 
• Gastroesophageal intussusceptions present 
with the most acute and severe clinical signs 
compared to more aborad locations.
• Recent foreign body ingestion. •  Previous or 
current enteropathy. •  Vomiting. •  Diarrhea. 
• Hematochezia. •  Hematemesis. •  Melena. 
• Abdominal pain. •  Abdominal distention. 
• Decreased appetite or anorexia. •  Weight 
loss. •  Historical findings are typically acute in 
onset, but chronic cases are reported.
• Abdominal pain. •  Palpation of thickened 
tube of bowel. •  Tachycardia from hypo­
volemia and pain. •  Bradycardia if significant 
vagal nerve stimulation has occurred. 
• Prolonged or rapid capillary refill time. 
• Thin body condition. •  Fever. •  Ileocolic 
intussusceptions may present with protrusion 
of the intussusceptum from the rectum; this 
can be differentiated from a rectal prolapse via 
probing along the side of the protruding tissue; 
the presence of a blind ­ending fornix indicates 
the existence of a rectal prolapse.
CAUSES
• Any disease that alters GI motility. •  Acute 
or chronic enteropathy and enteritis. 
• Recent abdominal surgery. •  Intestinal 
mural disease or intraluminal foreign body. 
• Intestinal parasitism. •  Less common 
causes include renal allograft transplantation 
(8–33% incidence) and hematopoietic cell 
grafts (5% incidence) in dogs. The reason for 
this relationship is unclear.
Presence of any condition listed under 
Causes.
  DIAGNOSIS
Any disease that can cause vomiting and 
diarrhea, including intestinal parasites; viral 
enteritis; bacterial enteritis; intraluminal 
foreign bodies; chronic enteropathy; 
mesenteric volvulus; GI neoplasia.
• Leukogram—leukopenia: especially with 
sepsis or parvoviral infection; leukocytosis: 
either stress response, acute inflammation, or 
sepsis. •  Hematocrit—elevated if dehydration 
or underlying hemorrhagic gastroenteritis; 
decreased: GI hemorrhage. •  Biochemical 
analysis—derangements of electrolytes due to 
loss through vomiting or diarrhea (may include hyponatremia, hypochloridemia, 
hypokalemia); azotemia (prerenal) if 
significantly dehydrated; hypoalbuminemia 
due to intestinal luminal loss from chronic 
protein ­losing enteropathy or acute changes 
in bowel wall integrity and permeability. 
• Urinalysis—may reveal elevated specific 
gravity in response to dehydration.
• May see hyperlactatemia secondary to 
vascular compromise to intestinal segment. 
• Blood gas evaluation may reveal a metabolic 
acidosis secondary to dehydration and 
hypoperfusion. •  Alternately, if the obstruction 
results in primarily gastric vomiting (pyloric 
obstruction), a hypochloremic, hypokalemic, 
metabolic alkalosis may be present.
IMAGING
• Plain abdominal radiographs may reveal an 
obstructive intestinal pattern—the degree of 
intestinal distention may be related to the 
degree of obstruction; may or may not reveal a 
soft tissue mass consistent with the intussus ­
ception. •  With gastroesophageal intussuscep ­
tion, a soft tissue mass may be seen within the 
lumen of the esophagus near the esophageal 
hiatus of the diaphragm—may be confused 
with a hiatal hernia, but the severity of the 
clinical signs typically associated with a hiatal 
hernia is less severe compared to the often 
peracute presentation associated with 
gastroesophageal intussusception. 
• Abdominal ultrasound is useful in the 
diagnosis of intussusceptions—the small 
intestinal intussusception appears as a target 
patterned mass on transverse sections, and as a 
multitude of parallel lines on longitudinal 
sections. •  Upper GI contrast studies or 
barium enemas can be helpful in supporting 
the diagnosis of an intussusception.
Upper GI endoscopy will definitively identify 
gastroesophageal intussusception and 
differentiate it from hiatal hernia.
 PATHOLOGIC FINDINGS
• Gross examination of the intussusception 
reveals telescoping of a segment of bowel into the 
adjacent segment. •  Histopathologic examination 
reveals variable degrees of venous and lymphatic 
congestion, vascular compromise, bowel wall 
necrosis, and peritonitis.
  TREATMENT
• Initial efforts should be focused on patient 
stabilization as well as correction of dehydration 
and existing electrolyte abnormalities. •  GI 
obstruction caused by intussusception is a 
surgical emergency; proceed with surgery once 
patient is stabilized.

Canine and Feline, Seventh Edition  789
I
• IV fluid administration to correct 
dehydration as well as replace anticipated 
ongoing losses through vomiting and 
diarrhea. •  Specific rate of administration 
and choice of fluid type are dictated by 
patient status and electrolyte derangements.
ACTIVITY
Recommend controlled activity for 10–14 
days postoperatively.
DIET
• Postoperative anorexia may be due to pain, 
nausea, and/or esophagitis. •  Nasal ­
esophageal, esophageal, or gastric feeding 
tubes may be indicated—enteral nutrition is 
required for intestinal mucosal healing and is 
preferred; enteral nutrition should be 
provided within the first 24 hours after 
surgery, once the patient is awake from 
anesthesia, at normal body temperature, and 
treatment of pain, ileus, nausea, and vomiting 
have been initiated. •  If patient is vomiting, a 
postpyloric feeding tube may be indicated.
• Communication centered on the 
importance of the identification and 
treatment of an underlying cause. 
• Complications may include perioperative 
mortality, septic peritonitis, or protracted 
hospital stay related to dehydration, 
hypovolemia, regurgitation, vomiting, blood 
loss, and peritonitis. •  Recurrence rates have 
been reported to be 6–27%.
• Surgical correction should be performed as 
soon as the patient is stable enough to 
undergo anesthesia and surgery. •  Once 
identified, all intussusceptions are a surgical 
emergency. •  A full abdominal exploratory is 
always performed for the identification of any 
potential underlying causes; full ­thickness 
biopsy of the bowel is recommended. 
• Multiple intussusceptions may be present. 
• Some intussusceptions can be manually 
reduced by gently milking the intussusceptum 
from within the intussuscipiens; upon 
reduction, the bowel may or may not be 
viable. •  In the event that manual reduction 
is not possible, or the bowel has questionable 
viability, an intestinal resection and anasto­
mosis is necessary. •  Surgical enteroplication 
has been proposed as a procedure for 
preventing recurrence. ◦ The rate of side 
effects and complications associated with 
enteroplication may be higher than the 
recurrence rate. ◦ It is important to exercise 
care when performing this procedure. 
◦ Briefly, the loops created in the bowel 
should be gentle, and sharp turns in the 
bowel loops are to be avoided; the submu­
cosal layer of the adjacent loops of bowel 
should be included in the sutures, but the 
lumen should not be entered.  MEDICATIONS
• Perioperative antibiotics are recommended—
manual reduction of an intussusception is 
considered a clean surgical procedure, while an 
intestinal resection and anastomosis is considered 
a clean contaminated procedure; septic peritonitis 
is considered a dirty/infected procedure. 
• Long ­term antibiotic administration is not 
recommended, except in cases in which septic 
peritonitis is present either preoperatively or 
postoperatively.
Some surgeons believe that drugs with 
promotility properties are contraindicated 
postoperatively in patients with intussus­
ception, but reports of such drugs causing 
recurrence is lacking.
N/A
N/A
N/A
  FOLLOW-UP
• Postoperatively, patients should be 
maintained on IV fluids. •  Pain ileus, nausea, 
and vomiting should be treated. •  Most 
recurrences occur within the first few days of 
surgery, but recurrences have been reported up 
to 3 weeks after surgery. •  Intestinal dehiscence 
typically occurs 3–5 days postoperatively, as 
collagenase and matrix metalloproteinase levels 
rapidly increase at the anastomosis site.
Prevention of many of the underlying causes can 
be achieved through such actions as vaccination, 
intestinal parasite control, and limiting 
situations in which patients can be exposed to 
dietary indiscretion or foreign body ingestion.
• Recurrence—6–27% of patients. •  Septic 
peritonitis—may result from postoperative 
intestinal dehiscence or intraoperative 
contamination. •  Short bowel syndrome is a 
rare complication that can occur with massive 
resections (generally >70% in dogs) of the 
small intestine.
Highly dependent upon underlying cause, 
location of intussusception, and condition at 
presentation. •  In general, the prognosis 
improves as the location of the intussus­
ception moves more aborad. •  Gastroesophageal intussusceptions have a grave prognosis with 
mortality rates approaching 95%, while 
intestinal intussusceptions have a good 
• Intestinal parasites. •  Viral enteritis. 
• Intestinal mural diseases. •  Gastroesophageal 
intussusceptions are typically associated with an 
underlying esophageal disorder or gastric 
motility disorders.
• Younger patients are typically affected with 
underlying enteritis (viral or bacterial) or 
intestinal parasitism. •  Older patients are more 
commonly affected with intestinal neoplasia.
Some underlying causes may be zoonotic 
(parasitic, bacterial, and protozoal causes of 
enteritis).
N/A
SYNONYMS
N/A
SEE ALSO
• Gastrointestinal Obstruction. •  Peritonitis.
Applewhite AA, Cornell KK, Selcer BA. 
Diagnosis and treatment of intussusceptions 
in dogs. Compend Contin Educ Pract Vet 
2002, 24:110–127.
Burkitt JM, Drobatz KJ, Saunders HM, 
Washabau RJ. Signalment, history, and 
outcome of cats with gastrointestinal tract 
intussusception: 20 cases (1986–2000). J 
Am Vet Med Assoc 2009, 234:771–776.
Nordquist B, Culp W. Focal and linear 
gastrointestinal obstructions. In: Monnet E, 
ed., Small Animal Soft Tissue Surgery. 
Ames, IA: Wiley ­Blackwell, 2013, p. 360.
Oaks MG, Lewis DD, Hosgood G, et al. 
Enteroplication for the prevention of 
intussusception recurrence in dogs: 31 cases. 
J Am Vet Med Assoc 1994, 205:72–75.
Patsikas MN, Jakovljevic S. Moustardas N. 
Ultrasonographic signs of intestinal 
intussusception associated with acute 
enteritis or gastroenteritis in 19 young dogs. 
J Am Anim Hosp Assoc 2003, 39:57–66.
available online(continued)  Intussusception

790  Blackwell’s Five-Minute Veterinary Consult  
IIris Atrophy
  BASICS
OVERVIEW
• Degeneration of iris tissues; both the iris 
stroma and posterior iris epithelium can be 
affected, resulting in loss of iris sphincter and 
dilator muscle function, atrophy of iris 
vessels, and loss of iris pigment.
• Both the pupillary margin and more 
peripheral portions of the iris can be affected, 
resulting in an iris that is thin or has areas of 
full‐thickness tissue loss.
• Senile or secondary change.
• Secondary iris atrophy is usually a result of 
chronic inflammation (uveitis).
• Iris sphincter muscle is frequently affected 
by atrophy, resulting in incomplete pupillary 
constriction, unequal pupil size (anisocoria), 
and possibly abnormal pupil shape (dyscoria).
• Irregular scalloped, moth‐eaten pupil 
margin is a common manifestation.
• Pupil margin may remain unaffected; 
peripheral loss of iris tissue can cause large 
holes in the iris that resemble multiple 
pupillary openings.
• Vision largely unaffected.
• Dog—common aging change; all breeds, 
but affects small breeds (e.g., miniature and 
toy poodles, miniature schnauzers, 
Chihuahuas) more commonly.
• Cat—uncommon; most common with blue 
irides.
• Secondary—any breed of dog or cat.
SIGNS
• Large or dyscoric pupil in one or both eyes.
• Photophobia.
• Previous episodes of uveitis.
• Incomplete or absent pupillary light reflex 
accompanied by normal menace response and 
dazzle reflex.
• Anisocoria may be present with unilateral 
or asymmetric presentation.
• Irregular, scalloped edge to pupillary 
margin; dyscoria (see Web Figures 1 and 2).
• Tapetal reflex visible through thin or absent 
areas of the iris on transillumination—
translucent patches or holes within the iris 
stroma: may resemble additional pupils.
• Strands of iris arising from free pupillary 
margin occasionally remain, spanning across 
portions of the pupil (Web Figures 1 and 2).
• Secondary—may be accompanied by any 
sign associated with chronic uveitis.
• Normal aging.
• Uveitis.
• Glaucoma.  DIAGNOSIS
• Must differentiate from congenital iris 
anomalies:
◦ Iris aplasia—rare in dog and cats.
◦ Iris hypoplasia—differentiate based on 
age at first presentation of signs.
◦ Iris coloboma—complete, full‐thickness 
area of lack of development of all layers of 
the iris; frequently associated with the merle 
condition; may also see associated lack of 
lens zonules and indentation of the lens 
posterior to the colobomatous iris area; 
differentiate based on age and presence of 
associated abnormalities.
◦ Polycoria—more than one pupil, each 
with ability to constrict due to presence of 
an iris sphincter.
◦ Persistent pupillary membranes—arise 
from collarette (midportion) of the iris, not 
from the free pupillary margin.
• Pupil dilation due to glaucoma—elevated 
intraocular pressure (IOP), corneal edema, 
conjunctival ± episcleral vascular injection, 
enlargement of globe may also be present; 
may also be blind.
• Adhesions of iris to lens or cornea 
(posterior or anterior synechia) as a result of 
uveitis or trauma—differentiate based on 
associated abnormalities consistent with 
uveitis or perforating trauma (e.g., full‐
thickness corneal scar).
N/A
N/A
IMAGING
N/A
Tonometry—low IOP possible if secondary 
to uveitis; high IOP if secondary to glaucoma 
or if uveitis has also caused secondary 
glaucoma; normal IOP if primary senile iris 
atrophy.
  TREATMENT
• Irreversible.
• Secondary—successful treatment aimed at 
controlling the underlying disease may halt 
progression of the condition.
• Patient may exhibit photophobia because of 
inability to constrict the pupil; provide 
adequate shade.  MEDICATIONS
• Senile—none.
• Secondary—depending on underlying 
disease.
Topical atropine—exacerbates pupillary 
dilation and photophobia.
  FOLLOW‐UP
• Senile—may continue to progress with age.
• Secondary—usually does not progress once 
primary disease is controlled.
SEE ALSO
canine anterior uvea. In: Gelatt KN, Gilger 
BC, Kern TJ, eds., Veterinary 
Ophthalmology, 5th ed. Ames, IA: Wiley‐
Blackwell, 2013, pp. 1146–1198.

Canine and Feline, Seventh Edition  791
IIron Toxicosis
  BASICS
OVERVIEW
• Iron is an essential metal for mammals; 
overdose results in clinical signs and potential 
death. • Absorption increases with readily 
ionized and soluble iron. • Oral sources may 
include dietary supplements (multivitamin, 
prenatal), snail and slug baits, single-use 
heat-producing packs (hand warmers), 
fertilizers, most oxygen absorber packets; 
overdoses of injectable iron may occur. 
• Oral overdose leads to disruption of 
gastrointestinal (GI) mucosa allowing greater 
iron absorption, resulting in possible 
systemic toxicity. • Potential organ systems 
involved include GI, cardiovascular (CV), 
hepatobiliary, nervous, hemic, and renal. 
• Tissue damage occurs due to free radical/
reactive oxygen species formation resulting in 
direct or secondary damage through 
processes such as lipid peroxidation. 
• Disrupts mitochondrial function and 
interferes with cellular respiration.
• Predominantly dogs, uncommon in other 
species. • All ages susceptible.
SIGNS
• History of iron ingestion or injectable 
overdose. • Initial signs related to GI 
irritation and mucosal damage; onset of signs 
occurs within 6–8 hours post ingestion; may 
include vomiting, diarrhea, mucosal damage 
(hematemesis, melena), abdominal pain and 
depression; signs with mild to moderate 
ingestions may not progress beyond GI. • In 
absence of significant initial GI signs, 
systemic toxicity unlikely. • A quiet/latent 
period may follow initial GI signs and last up 
to 24 hours post ingestion. • In severe cases, 
recurrence of clinical signs occurs 12–96 
hours post ingestion and can include ongoing 
vomiting/diarrhea ± mucosal damage, 
tachycardia, hypotension, CV collapse, 
metabolic acidosis, shock, hepatic necrosis, 
coagulopathy/disseminated intravascular 
coagulation (DIC), acute kidney injury, 
seizures, death. • Following GI involvement, 
scarring and stricture formation may occur 
during healing.
• Ingestion of iron-containing medication or 
other materials. • Majority of cases due to 
canine dietary indiscretion. • Elemental/
absorbable iron results in mild signs at 
20 mg/kg PO and severe signs at 60 mg/kg; 
other forms of iron including iron salts 
require conversion to elemental iron for dose 
calculations. • Metallic iron and iron oxide 
(rust)not readily ionizable/absorbable and 
toxicity not expected.  DIAGNOSIS
Other causes of severe gastroenteritis and 
shock, viral/bacterial enteritis, caustic/
corrosive ingestion, other dietary indiscretion, 
gastric torsion, heatstroke, snake bite.
• Leukocytosis. • Anemia (blood loss) or 
hemoconcentration. • Normal to high 
aspartate aminotransferase (AST), alanine 
aminotransferase (ALT), alkaline phosphatase 
(ALP), serum bilirubin.
• Blood gas to monitor for metabolic 
acidosis. • Serum iron levels ± total iron 
binding capacity (TIBC); serum iron level 
more commonly performed and drawn 
4–6 hours post ingestion with capsule or 
tablet ingestion and 2–3 hours post ingestion 
with liquid or chewable tablets; repeat q2–4h 
until peak level if able. • Hemolyzed serum 
samples increase iron content and should be 
avoided. • ECG/blood pressure. 
• Coagulation profile for DIC.
IMAGING
Abdominal radiography—iron-containing 
material may be radiopaque; adherence to 
mucosa may be visible.
Analysis of GI or stomach contents may aid 
in documenting high iron exposures.
• Primary gross lesions—hemorrhage in GI 
tract and liver; hepatomegaly. 
• Histopathologic lesions—GI necrosis with 
potential of hepatocellular and vascular 
endothelial necrosis.
  TREATMENT
• Inpatient monitoring with toxic doses; 
home monitoring if patient remains 
asymptomatic during initial 8 hours post 
ingestion; continue inpatient care if 
symptomatic. • Correct hypovolemic shock 
with IV fluids. • Correct severe acidosis with 
IV sodium bicarbonate. • Feed patient bland 
diet depending on GI status.
• Oral milk of magnesia or aluminum 
hydroxide (precipitates iron in GI tract) at 
5–30 mL PO q8–12h × 24h; may cause 
diarrhea. • Induce emesis or gastric lavage (if 
emesis contraindicated). • Emergency 
gastrotomy if lavage fails to remove adherent 
pills or bezoars. • Whole bowel irrigation or 
enema.  MEDICATIONS
Chelation
• Chelate when serum iron >350–500  𝜇g/dL or 
serum iron >TIBC. • Deferoxamine mesylate 
(40 mg/kg IM q4–8h) until urine no longer 
becomes reddish brown after treatment; IV 
administration at 15 mg/kg/h CRI reserved for 
critical patients. • Continue therapy until signs 
resolved and serum iron below 300  𝜇g/dL.
Other
• Antiemetic (maropitant 1 mg/kg SC/IV 
q24h). • GI protectant—proton pump inhibitor 
(omeprazole 1 mg/kg PO q24h); sucralfate 
(0.5–1 g PO q8–12h). • Ascorbic acid once iron 
fully removed from GI tract to enhance 
excretion (10–15 mg/kg q4–6h PO/SC/IM/IV).
• Activated charcoal does not bind iron. 
• Avoid gastric lavage in presence of 
hematemesis due to increased risk of 
perforation. • Administer IV deferoxamine 
slowly or may precipitate cardiac arrhythmias.
  FOLLOW-UP
• Liver enzymes—monitor up to 24 hours after 
excess circulating iron controlled. • Watch for 
evidence of GI stricture formation/obstruction. 
• Prognosis generally good with early treatment; 
decreases once signs of iron toxicosis develop or 
with very large ingestions.
SEE ALSO
alanine aminotransferase. • AST = aspartate 
aminotransferase. • CV = cardiovascular. 
• DIC = disseminated intravascular coagula-
tion. • GI = gastrointestinal. • TIBC = total 
iron binding capacity.
Hall JO. Iron. In: Peterson ME, Talcott PA, eds., 
Small Animal Toxicology, 3rd ed. Philadelphia, 
PA: W.B. Saunders, 2012, pp. 595–600.
Author  Sarah R. Alpert
Jeffery O. Hall.

792  Blackwell’s Five-Minute Veterinary Consult  
IIvermectin and Other Macrocyclic Lactones Toxicosis
  BASICS
OVERVIEW
• Ivermectin, milbemycin, moxidectin, 
selamectin, others. • Toxicity—dogs given large 
extra-label dosages ( >10–15 times recommended 
dosage). • Ivermectin—binds to glutamate-gated 
chloride ion channels in invertebrate nerve and 
muscle cells causing subsequent paralysis and 
death of the parasite. Also interacts with other 
ligand-gated chloride channels, including those 
gated by 𝛾-aminobutyric acid (GABA). 
• Sensitivity—collies and certain other breeds 
are more sensitive to high doses of ivermectin. 
This sensitivity has been associated with an 
inherited deletion of the ABCB1-1∆ gene that 
encodes a transmembrane protein pump called 
P-glycoprotein. P-glycoprotein is believed to 
transport ivermectin out of brain tissue and into 
circulation.
• Dogs. • Collies—most commonly affected. 
• Dogs homozygous for the ABCB1-1∆ gene 
deletion also affected; heterozygous dogs can 
react at higher doses. The ABCB1-1∆ gene 
mutation has been found in Shetland 
sheepdogs, Australian shepherds, Old English 
sheepdogs, German shepherds, English 
shepherds, longhaired whippets, silken 
windhounds, and a variety of mixed-breed dogs. 
• No age or sex predilections.
SIGNS
• Mydriasis. • Depression. • Drooling/
salivation. • Vomiting. • Ataxia. • T remors. 
• Disorientation. • Weakness, recumbency. 
• Nonresponsiveness. • T ransient blindness. 
• Bradycardia. • Hypoventilation. • Coma. 
• Death.
• Extra-label use at high dosage. • Breed 
sensitivity—see above. • T reating 
demodicosis with high-dose ivermectin while 
patient is on spinosad.
  DIAGNOSIS
• History and clinical signs. • No specific 
tests useful.
• Overdoses of other insecticides such as 
pyrethrins, pyrethroids, organophosphorus, 
and carbamate compounds. • Other 
toxicants, such as loperamide or diseases 
affecting CNS.
N/A
Arterial blood gases—may reveal high partial 
pressure of carbon dioxide (PaCO2) and low partial pressure of oxygen (PaO2) from 
respiratory depression and hypoventilation.
Physostigmine 1 mg IV; temporary (30–40 
min) return to consciousness or resumed 
alertness and muscle activity after administra-
tion supports but does not confirm diagnosis; 
does not speed recovery; not indicated for 
treatment; glycopyrrolate administered first 
may prevent severe bradycardia.
  TREATMENT
• Supportive and symptomatic care. • If 
patient alert and able to swallow, activated 
charcoal repeated every 6–8 hours; monitor 
for hypernatremia. • Use of IV lipid emulsion 
has been successful in ameliorating clinical 
signs in many cases; recent literature has 
conflicting data on effectiveness in dogs with 
ABCB1-1∆ homozygous mutations. 
• Important goals—proper fluid therapy, 
maintenance of electrolyte balance, 
nutritional support, and prevention of 
secondary complications. • Nutritional 
support—institute early, preferably within 
2–3 days of exposure; severe CNS depression 
or coma may last for days or weeks depending 
on severity of exposure. • Good nursing care 
for recumbent patient. • Ocular lubricants. 
• Mechanical ventilation—may be required 
with respiratory depression.
• No known reversal agent. • Atropine or 
glycopyrrolate—may be administered as 
needed to treat bradycardia. • 20% 
intravenous lipid emulsions—bolus dose 
1.5 mL/kg over 2–3 min; CRI of 0.25 mL/
kg/min for 30–60 min; check serum q2h and 
if not lipemic; repeat as needed; if no clinical 
improvement after three doses, discontinue.
• Other drugs known to cause toxicity in 
dogs with ABCB1 mutation—loperamide, 
doxorubicin, vincristine, vinblastine, 
acepromazine, butorphanol, emopside, and 
erythromycin. • Do not use ivermectin 
concurrently with ketoconazole. 
• Concomitant extra-label use of ivermectin 
and spinosad may produce clinical signs.
  FOLLOW-UP
• Prognosis and eventual outcome—depends 
on individual and breed sensitivity, amount of drug ingested or injected, how rapidly clinical 
signs develop, response to supportive 
treatment, and overall health of patient. 
• Convalescence may be prolonged (several 
weeks); good supportive care in many 
seemingly hopeless cases has resulted in 
complete recovery.
SEE ALSO
• GABA = 𝛾-aminobutyric acid.
• PaCO2 = partial pressure of carbon dioxide. 
Crandell DE, Weinberg GI. Moxidectin 
toxicosis in a puppy successfully treated 
with intravenous lipids. J Vet Emerg Crit 
Care 2009, 19(2):181–186.
Gupta, Ramesh C., ed. Veterinary Toxicology: 
Basic and Clinical Principles, 3rd ed. San 
Diego, CA: Elsevier, 2018, pp. 539–550.
Mealy KL. Canine ABCB1 and macrocyclic 
lactones: heartworm prevention and 
pharmacogenetics. Vet Parasitol 2008, 
158:215–222.
Author  Dominic A. Tauer
Allan J. Paul

Canine and Feline, Seventh Edition  793
JJoint Luxations
  BASICS
Luxation is the complete disruption of the 
contiguous articular surfaces of a joint when 
the supporting structures around the joint are 
damaged or missing. Subluxation is a partial 
disruption.
• Synovial joints have a joint capsule that joins 
the articulating bones together. The fibrous 
layer of this capsule is a primary stabilizer of 
the joint. Most joints have additional 
ligaments that reinforce the joint capsule to 
improve the resistance to movement outside of 
the normal range of motion of that joint. All 
motion joints also have a system of muscles 
and tendons that exert forces on the joint to 
control movement and prevent subluxation of 
the joint. The co-contraction forces around a 
joint are very influential on the stability of the 
joint. Instability occurs when the stabilizing 
system is damaged, disrupted, or does not 
develop normally. • If laxity is clinically 
apparent, then the instability is generally 
described as luxation or subluxation of the 
joint. • Luxation may occur as a result of 
traumatic forces causing the joint to move 
beyond the elastic limits of the supporting 
tissues. • Secondary changes are set in motion 
by damage to the tissues that creates early, and 
then later, more chronic joint damage.
• Musculoskeletal—primarily the intra-
articular environment and the support 
structures around the joint, including joint 
capsule, fibrocartilage, collateral ligaments, and 
supporting muscle/tendon units. 
• Neurologic—neurologic feedback and supply 
to the support system may also be affected.
GENETICS
• Hyperlaxity syndrome is an inherited trait in 
humans. Puppies may show temporary hyperlaxity 
when confined or when housed on poor substrates. 
• Hip dysplasia is a form of inherited laxity of the 
coxofemoral joint. • Shoulder luxation is an 
inherited predisposition in small breeds, such as 
miniature poodles. • Femoropatellar instability 
leading to medial patellar luxation is a common 
inherited disease in small-breed dogs. • Ehlers–
Danlos syndrome is a congenital collagen disorder 
that leads to generalized joint laxity.
Various forms of laxity/luxation (specifically 
hip dysplasia and medial patella luxation) are 
very common. Other forms such as Ehlers–
Danlos syndrome are extremely uncommon.
Species
All species.Breed Predilections
• T raumatic luxation has not been shown to be 
breed specific in any joint. • Breed predi -
lection for nontraumatic luxations varies with 
the joint affected. • Hip—large breeds show 
clinical signs of hip dysplasia more frequently 
than smaller breeds, but breeds of all sizes can 
have radiographic signs. • Congenital shoulder 
luxation occurs most commonly in miniature 
breeds (miniature poodle). • Medial patella 
luxation is more common in small-breed dogs.
• T raumatic—any age. • Congenital laxity/
luxation is typically seen in the juvenile dog, 
with secondary degenerative joint disease 
showing later in life.
SIGNS
• Acute swelling, pain, and non-use of the 
limb are usually seen with acute luxation. 
Partial weight-bearing may occur with 
subluxation or chronic luxation. • Abnormal 
anatomic position of one bone in relation to 
the adjoining bone. • Hip luxation is 
commonly craniodorsal (the displacement of 
the femoral head in relation to the 
acetabulum). • Shoulder luxation is 
commonly medial. • Elbow luxation is 
commonly proximolateral. • Carpal and 
tarsal luxations commonly result in varus, 
valgus, or hyperextension when stressed.
CAUSES
• T raumatic overstress of normal soft tissues 
beyond their elastic limit. • Fracture of the 
bone attaching the origin or insertion of a 
tendon or ligament to the body of the bone. 
• Minimal stress on abnormally unstable 
joints of congenital etiology.
• Abnormal congenital conformation, 
causing altered joint stresses. • Fatigue, 
causing muscle weakness and incoordination. 
• Neurologic derangement. • Environments 
conducive to traumatic events.
  DIAGNOSIS
• Fractures. • Joint disease—immune-
mediated, septic, or degenerative.
• No abnormalities expected that are directly 
related to the luxation. • T rauma-induced 
abnormalities in traumatic situations.
Arthrocentesis may help to rule out 
nontraumatic joint disease.
IMAGING
• Radiographs confirm the diagnosis by 
documenting the anatomic malalignment. 
• Radiographs to rule out other pathology, such as intra- or extra-articular fractures that 
could affect the decision to perform closed 
reduction. • Stress views may be needed in 
some situations.
• Palpation of the laxity/luxation (ex. 
ortolani, cranial drawer, medial patella 
luxation, stress-induced laxity/instability). 
• Palpation of the position of the displaced 
bone.
• T rauma-induced hemorrhage, edema, and 
disruption of ligaments and joint capsule. 
• Secondary changes related to degenerative 
joint disease.
  TREATMENT
Closed Reduction
• Closed reduction is attempted if: there is no 
underlying intraarticular pathology (fracture); 
there is adequate intact support structures to 
maintain marginal stability immediately after 
reduction; there is no underlying dysplasia 
that predisposes the joint to luxation (as this 
would increase the chance of reduction 
failure); there is no additional pathology in 
other limbs that would require immediate 
weight-bearing of the affected limb. • Closed 
reduction is often considered the first line of 
treatment (when appropriate) for hip 
luxations (craniodorsal and caudoventral), 
shoulder luxation, and elbow luxations. 
• Surgical stabilization is often required with 
carpal, tarsal, and stifle luxations. • Surgical 
intervention (arthrodesis) or long-term brace 
(orthotic) are required for palmar or plantar 
instability due to the excessive stresses placed 
on palmar and plantar ligaments and 
fibrocartilage in the dog and cat.
Immobilization
Immobilize the joint with a bandage/splint if 
the affected joint is distal to the inguinal or 
axial areas.
External Coaptation (Maintenance 
Period)
• Craniodorsal hip luxation—ehmer sling 
(~14 days). • Caudoventral hip luxation—
hobbles (~14 days). • Elbow luxation—  
spica splint (~14 days). • Shoulder luxation 
(medial)—valpeau sling (~14 days). 
• Shoulder luxation (lateral)—spica splint 
(~14–21 days). • Tarsocrural and radio -
carpal instability (except palmar and plantar 
instability)—cast or medial/lateral splint 
(6–10 weeks depending on degree of injury). 
• Medial, lateral, or dorsal pes and manus 
instability caudal spoon splint or cast (6–10 
weeks depending on degree of injury).

794  Blackwell’s Five-Minute Veterinary Consult  
JNURSING CARE
• Rest, exercise restriction, pain control, and 
maintenance of external coaptation. • Cold 
compresses for 5–10 minutes four or five 
times a day initially to reduce inflammation.
ACTIVITY
Cage rest for joint stabilization period, then 
slow return to function to encourage healing 
and strengthening of soft tissue support of the 
limb.
DIET
Normal
Activity and weight gain increase the likelihood 
of degenerative changes in the long term.
• Surgery is typically required for spinal 
luxations. • For appendicular skeleton for 
which closed reduction is ideal, an open 
surgical approach is preferred if: closed 
reduction fails; there is evidence of predispos -
ing joint dysplasia; there is evidence of an 
intra-articular fracture; there is concurrent 
pathology that requires early stability and 
weight-bearing on the affected limb. • With 
open reduction, stabilization via prosthetic 
ligament placement, ligament reconstruction, 
or temporary transarticular stabilization is 
considered. • Salvage procedures include 
prosthetic joint replacement, surgical removal 
of bone-to-bone contact points (femoral 
head and neck ostectomy), arthrodesis, and 
amputation. Arthrodesis is the first line of 
treatment for all palmar and plantar 
luxations of the pes or manus.
(NSAIDs) decrease prostaglandin synthesis by 
inhibiting cyclooxygenase enzymes: 
◦ Carprofen 2.2 mg/kg PO or SC q12h, or 
4.4 mg/kg PO or SC q24h. ◦ Deracoxib 
1–2 mg/kg PO q24h. ◦ Firocoxib 5 mg/kg 
PO q24h. ◦ Grapiprant 2 mg/kg PO 
q24h—for canines. ◦ Meloxicam 0.1 mg/kg 
PO or SC q24h. ◦ Robenacoxib 1–2 tablets 
PO depending on weight q24h for 3 
days—for felines. • T ramadol 1–4 mg/kg PO q8–12h. • Gabapentin 5–10 mg/kg PO 
q8–12h.
• NSAIDs and gastrointestinal sensitivity. 
• NSAIDs and liver or renal pathology.
Stop medications if diarrhea or vomiting is 
seen.
• Other NSAIDs. • Steroids.
• Analgesics (opioids). • Fish oil supple -
mentation to decrease inflammatory mediator 
  FOLLOW-UP
• Always take a radiograph after reduction. 
• Some clinicians will evaluate reduction 3–5 
days after initial stabilization via radiographs 
to ensure surgical stabilization is not 
warranted (note—do not remove coaptation 
for radiographs as this will increase risk of 
reluxation). • Take follow-up radiographs 
when the splint/sling is removed (typically 
2–10 weeks post stabilization).
• Fenced-in yards. • Keep pets on a leash 
when outside. • Keep the sling in place 
for the duration of planned stabilization 
(for coaptation that is maintained for <3 
weeks).
• Reluxation. • Pressure sores from bandages 
and coaptation. • Clinical osteoarthritis. 
• Infection after surgery. • Implant failure of 
joint prosthetic.
• Return of function is expected unless a 
complication occurs. • Progressive 
degenerative joint disease.
OsteoarthritisAGE-RELATED FACTORS
None
If patient is pregnant, care should be taken to 
prescribe appropriate pain management.
SYNONYMS
Dislocation
SEE ALSO
• Hip Dysplasia.
drug.
Alam MR, Lee JI, Kang HS, et al. Frequency 
and distribution of patellar luxation in dogs: 
134 cases (2000 to 2005). Vet Comp 
Orthop T raumatol 2007, 20(1):59–64.
DeCamp CE. Brinker, Piermattei and Flo’s 
Handbook of Small Animal Orthopedics 
and Fracture Repair, 5th ed. St. Louis, MO: 
Elsevier Health Sciences, 2016.
Evers P , Johnston GR, Wallace LJ, Lipowitz 
AJ, King VL. Long-term results of 
treatment of traumatic coxofemoral joint 
dislocation in dogs: 64 cases (1973–1992). J 
Am Vet Med Assoc 1997, 210(1):59–64.
Kieves NR, Lotsikas PJ, Schulz KS, Canapp SO. 
Hip toggle stabilization using the TightRope® 
system in 17 dogs: technique and long-term 
outcome. Vet Surg 2014, 43:515–522.
McLaughlin RM. T raumatic joint luxations 
in small animals. Vet Clin North Am Small 
Anim Pract 1995, 25(5):1175–1196.
Authors  Victoria A. DeMello and Wesley J. 
Roach
Acknowledgments  The authors and editor 
Spencer A. Johnston and Caitlyn F . Connor.
available onlineJoint Luxations  (continued)

Canine and Feline, Seventh Edition  795
KKeratitis, Eosinophilic—Cats
  BASICS
OVERVIEW
• Presumed immune-mediated inflammation 
of the cornea characterized by perilimbal 
corneal vascularization, white-pink corneal 
infiltrate, and corneal edema.
• Synonym—proliferative keratitis.
Young adult to middle-aged cats.
SIGNS
• Variable ocular pain, often minimal.
• Serous to mucoid ocular discharge.
• Limbal superficial corneal vascularization 
90–360° (temporal or inferior nasal quadrants 
are first affected).
• White to pink, flat or raised granular 
corneal infiltrate.
• Multifocal, small, white gritty corneal deposits.
• Corneal ulceration may be present.
• Conjunctival and third eyelid hyperemia, 
chemosis, and thickening with possible 
cobblestone surface texture.
• Feline herpesvirus-1 (FHV-1) may be 
associated, but exact role is unclear.
• Exact etiopathogenesis unknown; proposed 
theories are: (1) type I hypersensitivity with 
IgE-mediated mast cell and eosinophil 
degranulation, (2) type IV reaction where 
sensitized T-lymphocytes stimulate 
eosinophil-mediated corneal damage.
• Bacterial and fungal infection are not 
consistent etiologic causes, although 
secondary bacterial keratitis may occur.
  DIAGNOSIS
• Chronic corneal ulceration with 
secondary corneal vascularization 
(granulation tissue).
• FHV-1 stromal keratitis—appears similar, 
but lacks proliferative component, with more 
severe ocular pain and corneal ulceration.
• Corneal neoplasia: (1) lymphoma—
concurrent conjunctival and/or uveal 
infiltration is common, (2) squamous cell 
carcinoma—rarely involves cornea in cats.
• Chlamydia psittaci  or Mycoplasma felis —
usually conjunctival diseases without corneal 
Peripheral eosinophilia may be present.
• PCR for FHV-1 has limited diagnostic value 
since healthy cats may have positive results.• Immunofluorescent antibody test (IFA) 
testing for Chlamydia psittaci .
• Corneal cytology provides definitive 
diagnosis and should be done first. Typically 
numerous eosinophils, free eosinophil granules 
and/or mast cells, neutrophils, lymphocytes, 
plasma cells, and epithelial cells are seen.
• Cytology helps rule out chlamydia and 
• Fluorescein staining to evaluate for corneal 
• Keratectomy and histopathology may 
confirm diagnosis in chronic or nonrespon-
sive cases.
  TREATMENT
• Topical corticosteroids—1% prednisolone 
acetate or 0.1% dexamethasone sodium 
phosphate q6–12h for 5–7 days, then 
gradually taper to the lowest effective 
frequency of application or discontinue.
• Topical 1–2% cyclosporine A q8–12h, then 
tapered to lowest effective frequency of 
application or discontinued. Can use in cats 
in which oral megestrol acetate and topical 
corticosteroids are contraindicated. May be 
irritating or cause blepharitis.
• Topical 0.5% megestrol acetate q8–12h 
initially, then tapered to lowest effective 
frequency or discontinued.
• Adjunctive topical or systemic antiviral 
therapy may be warranted in cases with 
history or clinical signs compatible with 
FHV-1 infection.
• Subconjunctival corticosteroids—
triamcinolone acetonide (0.1–0.2 mL q3–7 
days); only in cats that are difficult to treat 
with topical medications.
• Systemic prednisolone—2.2 mg/kg PO 
q12h and taper. Use only if a cat will not 
tolerate topical therapy or oral megestrol 
acetate.
• Megestrol acetate—2.5 mg PO q24h for 
3–5 days, then 2.5 mg PO q48h for 3–5 days, 
then gradually decrease frequency to the 
lowest effective frequency or discontinue.
• Topical corticosteroid administration may be 
associated with recrudescence of FHV-1 
keratoconjunctivitis and should be used and 
monitored carefully. Client should be advised 
to immediately report any adverse change in the condition of the eye (blepharospasm, 
corneal edema, increased ocular discharge, etc.).
• Megestrol acetate causes adrenal cortical 
suppression and may result in diabetes 
mellitus, polyphagia, temperament change, 
mammary gland hyperplasia, or neoplasia and 
pyometra. It should not be used in cats with 
hepatic disease or other illness.
  FOLLOW-UP
• Response to therapy is usually rapid.
• Complete resolution may take several days 
to months. May require long-term therapy.
• Corneal vascularization and infiltrate may 
resolve completely with minimal corneal 
scarring.
• Recurrences in both the short and long 
term are common.
Not typically associated with dermatologic 
• FHV-1 = feline herpesvirus-1.
• IFA = immunofluorescent antibody test.
Ophthalmology, 5th ed. Ames, IA: John 
Wiley & Sons, 2013, pp. 1496–1498.
Stiles J, Coster M. Use of an ophthalmic 
formulation of megestrol acetate for the 
treatment of eosinophilic keratitis in cats. 
Vet Ophthalmol 2016, 19(Suppl 1):86–90.

796  Blackwell’s Five-Minute Veterinary Consult  
KKeratitis, Nonulcerative
  BASICS
An inflammatory disorder of the cornea that 
does not retain fluorescein stain.
A pathologic response resulting in reduced 
corneal clarity secondary to edema, inflam-
matory cell infiltration, vascularization, 
pigmentation, lipid or calcium deposition, or 
scarring.
GENETICS
• No proven genetic basis in dogs or cats. 
• Chronic superficial keratitis (pannus)—
inherited predisposition in German shepherd 
dogs.
Chronic superficial keratitis is more common 
in regions of high UV light exposure.
Species
• Dog—chronic superficial keratitis (pannus); 
pigmentary keratitis; pigmentary keratopathy 
of pugs; nodular granulomatous episcleritis 
(NGE; see Episcleritis); keratoconjunctivitis 
sicca (KCS; see Keratoconjunctivitis Sicca). 
• Cat—eosinophilic keratitis (see Keratitis, 
Eosinophilic—Cats); herpesvirus (stromal 
form); corneal sequestrum; KCS uncommon, 
usually secondary to chronic herpesvirus 
Dogs
highest prevalence in German shepherd dogs 
and sighthounds. •  Pigmentary keratitis—
notably brachycephalic breeds with exposure 
keratopathy from lagophthalmia, tear film 
deficiencies, and trichiasis. •  Pigmentary 
keratopathy of pugs—suspected genetic 
condition that results in progressive corneal 
pigmentation, cause currently unknown. 
• NGE—prevalent in cocker spaniels, collies, 
and Shetland sheepdogs. •  KCS—
brachycephalic breeds, cocker spaniels, 
English bulldogs, West Highland white 
terriers, cavalier King Charles spaniels.
Cats
• Eosinophilic keratitis—most prevalent in 
domestic shorthair. •  Corneal sequestration—
most prevalent in brachycephalic breeds.
• Dogs: chronic superficial keratitis—any 
age, usually between 3-6 years (younger in sighthounds); pigmentary keratitis and 
pigmentary keratopathy of pugs may occur at 
any age; NGE—any age, mean 3.8 years in 
Collies; KCS—middle-aged to older dogs. 
• Cats: herpesvirus, eosinophilic keratitis, 
and corneal sequestrum—any age.
• Dogs—female predisposition reported for 
pannus and KCS. •  Cats—castrated male 
predisposition reported for eosinophilic 
keratitis.
SIGNS
Corneal discoloration and ocular discomfort.
Dogs
• Chronic superficial keratitis—usually 
bilateral, corneal vascularization range from 
superficial vessels to dense granulation tissue 
with variable pigmentation; lateral or 
ventrolateral cornea (entire cornea affected in 
advanced cases); thickened and depigmented 
third eyelids; white deposits (corneal 
degeneration) may be present at the leading 
edge of corneal lesion; may lead to blindness. 
• Pigmentary keratitis—Focal to diffuse 
brown discoloration of the cornea; often with 
corneal vascularization or scarring. 
• Pigmentary keratopathy of pugs—brown 
corneal pigmentation originating from medial 
cornea and progressing towards central 
cornea. •  NGE—bilateral or unilateral; 
raised, fleshy masses affecting the lateral 
limbus and cornea; corneal deposits, edema, 
and vascularization may occur in adjacent 
corneal stroma; slow to rapidly progressive; 
third eyelids may appear thickened. •  KCS—
unilateral or bilateral; mucoid ocular 
discharge, conjunctival hyperemia, corneal 
vascularization, pigmentation, and scarring; 
corneal ulceration may occur.
Cats
• Herpesvirus (stromal form)—unilateral or 
bilateral; stromal edema, infiltrates, deep 
vascularization and scarring; ulceration may 
occur; severe scarring may threaten vision. 
• Eosinophilic keratitis—usually unilateral; 
raised vascularized lesion with pink-white 
infiltrates forming gritty plaques; may retain 
fluorescein stain at the lesion’s periphery. 
• Corneal sequestrum—usually unilateral 
(can be bilateral); amber, brown, or black 
plaques on the central or paracentral cornea; 
vary in size and depth; edges may appear 
raised; corneal vascularization is variable; 
may retain fluorescein at periphery of 
lesion.
CAUSES
Dogs
• Chronic superficial keratitis—presumed to 
be immune-mediated; high altitude 
(increased UV radiation exposure) increases the prevalence and severity of disease. 
• Pigmentary keratitis—secondary to chronic 
corneal irritation; evaluate for primary 
underlying ocular conditions; frequently 
associated with exposure keratopathy and 
KCS. •  Pigmentary keratopathy of pugs—
unknown, may have genetic basis. •  NGE—
presumed to be immune mediated. 
• KCS—bilateral: usually immune-mediated 
or drug-induced; unilateral: congenital, 
iatrogenic, neurogenic.
Cats
• Herpesvirus (stromal form)—immune-
mediated T-cell lymphocyte reaction to 
herpesvirus antigen (vs. cytopathic effect of 
the virus). •  Eosinophilic keratitis—possible 
hypersensitivity reaction; high incidence of 
animals PCR positive for feline herpesvirus 
type 1 (FHV-1); fewer positive for Chlamydia -
like agents. •  Corneal sequestrum—
unknown; likely due to chronic corneal 
irritation or ulceration; suggested relationship 
with herpesvirus.
Dogs—chronic superficial keratitis more 
likely to occur at high altitudes.
  DIAGNOSIS
• Infectious keratitis is usually ulcerative and 
painful; cytology of the cornea reveals white 
blood cells, infectious organisms. In cats, 
stromal herpesvirus may be associated with 
ulcerative keratitis and secondary bacterial 
infection. •  Neoplasia—rare involvement of 
sclera or cornea; distinguish based on color, 
age of animal, breed predilection; usually 
unilateral; lack of response to topical 
anti-inflammatory therapy. Very rare in cats.
Dogs
• Schirmer tear test—values <15 mm/min 
suggest KCS but should be interpreted with 
breed and ocular findings. •  Cytologic 
examination of corneal or conjunctival 
scrapings—chronic superficial keratitis 
characterized by lymphocytes, plasma cells, 
and mast cells. •  Biopsy of episcleral nodular 
mass or cornea (superficial keratectomy)—for 
NGE diagnosis, can be considered for 
patients with chronic superficial keratitis.
Cats
• Conjunctival or corneal scraping—PCR 
most successful for diagnosis for herpesvirus 
(IFA or viral culture of limited value). 
Eosinophilic keratitis: eosinophils on 
cytology. •  Superficial keratectomy—
consider for diagnosis of eosinophilic keratitis 
or sequestrum but usually unnecessary.

Canine and Feline, Seventh Edition  797
K  TREATMENT
• Outpatient—generally sufficient. 
• Inpatient—cases that warrant surgery due 
to inadequate response to medical therapy.
Dogs
Typically lifelong treatment; disease is 
controlled rather than cured.
Cats
• Herpesvirus—ocular discomfort and keratitis 
often recur. •  Eosinophilic keratitis—disease 
controlled rather than cured. •  Corneal 
sequestrum—may slough spontaneously, 
however cornea may rupture; clinical course 
often protracted without surgery; removal of 
sequestrum by superficial keratectomy may be 
curative, although recurrence possible.
Dogs
• Chronic superficial keratitis—superficial 
keratectomy for severe disease in which vision 
is impaired due to corneal pigmentation; 
patients still require indefinite medical 
treatment to prevent recurrence; β-irradiation 
with a strontium-90 probe is noninvasive and 
may be performed in severe cases. 
• Pigmentary keratitis—superficial keratec -
tomy may be performed only after initial 
underlying cause is corrected; only in severe 
cases that threaten vision. •  Pigmentary 
keratopathy of pugs—high likelihood of 
recurrence after superficial keratectomy. 
• NGE—superficial keratectomy is diagnostic; 
medical treatment is still required. •  KCS—
parotid duct transposition or permanent 
partial tarsorrhaphy to reduce exposure.
Cats
• Eosinophilic keratitis—superficial keratec -
tomy is diagnostic but not curative; medical 
treatment is preferred. •  Corneal sequestrum—  
superficial keratectomy may be curative; 
recurrence is possible.
Dogs
• Chronic superficial keratitis—topical 
corticosteroids (1% prednisolone or 0.1% 
dexamethasone q6–12h); topical 0.2–2% 
cyclosporine, 1% pimecrolimus, or 0.03% 
tacrolimus q8–12h; agents can be used alone 
or in combination for more severe cases; 
subconjunctival corticosteroid injection (triamcinolone acetonide, 2–8 mg) can be 
used as an adjunct to topical therapy in severe 
cases. •  Pigmentary keratitis—treatment 
directed at underlying cause; topical 
corticosteroids if primary cause is 
inflammatory; lubricants and cyclosporine or 
tacrolimus if primary condition is KCS; 
cyclosporine or tacrolimus may reduce 
pigmentation in all cases. •  Pigmentary 
keratopathy of pugs—topical cyclosporine 
0.2–2% or tacrolimus 0.02–0.03% may arrest 
progression of corneal pigmentation; topical 
corticosteroids may temporarily reduce 
density of corneal pigment. •  NGE—topical 
corticosteroids and/or cyclosporine as 
described above; systemic azathioprine (2 mg/
kg/day PO, initially, then gradually reduce) 
may be effective when used alone or in 
combination with topical medications. 
• KCS—topical 0.2–2% cyclosporine, or 
0.02–0.03% tacrolimus q8–12h (see 
Keratoconjunctivitis Sicca).
Cats
• Herpesvirus—topical antiviral agents 
recommended: cidofovir 0.5% q12h or 
trifluridine q4–6h for 2 days, then taper. 
Systemic antiviral agents include: famciclovir 
90 mg/kg PO q12h. For inflammation, 
topical nonsteroidal anti-inflammatory drugs 
or cyclosporine q12h may be used. 
• Eosinophilic keratitis—topical corti -
costeroids (1% prednisolone or 0.1% 
dexamethasone) q6–12h; patient monitored 
for ulceration or worsening of clinical signs; 
topical antivirals can be used in combination 
with corticosteroids if concurrent herpesvirus; 
use of topical cyclosporine reported (0.2–
1.5%) with variable results; megestrol acetate 
(5 mg PO q24h for 5 days, then 5 mg PO 
q48h for 1 week, then 5 mg PO weekly for 
maintenance) is highly effective, but 
associated with side effects. •  Corneal 
sequestrum—topical antibiotic (terramycin or 
erythromycin) q8–12h for associated corneal 
ulceration; artificial tear lubrication may 
relieve discomfort; topical antivirals can be 
used if herpesvirus infection is suspected; 
topical 1% atropine ointment q12–24h for 
pain from concurrent uveitis if present.
Topical corticosteroids contraindicated with 
corneal ulcers; topical atropine contraindi-
cated with KCS, glaucoma, or lens luxation. 
Topical neomycin and polymixin may cause 
anaphylactic reactions in cats.
• Azathioprine may cause gastrointestinal 
signs, pancreatitis, hepatotoxicity, and 
myelosuppression. •  Megestrol acetate—not 
FDA-approved for use in cats; possible side 
effects include polyphagia, diabetes mellitus, 
mammary hyperplasia, mammary neoplasia, and pyometra. •  Famciclovir— anorexia, 
  FOLLOW-UP
Periodic ocular examination recommended to 
evaluate efficacy of treatment; examine at 1- 
to 2-week intervals, gradually lengthening the 
interval with remission or resolution of 
clinical signs; taper medications based on 
resolution of clinical signs; complete 
resolution of pigmentation may not occur. 
UV light protection (tinted goggles) is 
recommended for pannus.
All of the above may lead to continued ocular 
discomfort, visual defects, or blindness in 
SEE ALSO
• Episcleritis.
• Keratitis, Eosinophilic—Cats.
• Keratitis, Ulcerative.
• IFA = immunofluorescent antibody test. 
• NGE = nodular granulomatous episcleritis.
Andrew SE. Immune-mediated canine and 
feline keratitis. Vet Clin Small Anim 2008, 
38:269–290.
Chavkin MJ, Roberts SM, Salman MD, et al. 
Risk factors for development of chronic 
superficial keratitis in dogs. J Am Vet Med 
Assoc 1994, 204:1630–1634.
Labelle AL, Dresser CB, Hamor RE, et al. 
Characteristics of, prevalence of and risk 
factors for corneal pigmentation 
(pigmentary keratopathy) in pugs. J Am Vet 
Med Assoc 2013, 243:667–674.
Acknowledgments  The author/editor 
acknowledges the prior contribution of 
Amber L. Labelle. 
available online(continued)  Keratitis, Nonulcerative

798  Blackwell’s Five-Minute Veterinary Consult  
KKeratitis, Ulcerative
  BASICS
Inflammation of the cornea associated with 
loss of corneal epithelium (corneal erosion) or 
loss of variable amounts of underlying corneal 
stroma (corneal ulcer).
• May be caused by any condition (traumatic 
or nontraumatic) that disrupts corneal 
epithelium or stroma. •  Ulcers—superficial 
or deep, uncomplicated or complicated: 
◦ Superficial—involves epithelium and 
possibly superficial stroma. ◦ Deep—
involves a greater thickness of stroma and 
may extend to Descemet’s membrane 
(descemetocele), possibly leading to rupture 
of globe. ◦ Complicated—persistence of 
underlying/inciting cause, microbial 
infection, or production of degradative 
enzymes (melting). •  Epithelial wound 
healing—adjacent corneal epithelial cells 
loosen and begin migration over the defect 
within a few hours; mitosis occurs within a 
few days to restore normal epithelial 
thickness; healing process complete in 5–7 
days in uncomplicated, superficial ulcers. 
• Stromal wound healing—slower, more 
complex; can be in an avascular or vascular 
manner; in shallow wounds, epithelial 
migration may be sufficient to fill defect; 
epithelium may cover some deeper ulcers 
even when epithelium and stromal 
regeneration are insufficient to restore normal 
corneal thickness (nonulcerated divot defect 
is called a facet); stroma usually heals by 
fibrovascular infiltration, resulting in scarring. 
• Stromal ulcers—often complicated by 
microbial infection or enzymatic destruction 
initiated by microbial organisms, host 
inflammatory cells, or corneal epithelial or 
stromal cells; enzymatic destruction may 
result in gelatinous appearance of corneal 
stroma (“melting” or “malacic” ulcer).
GENETICS
• No proven basis; breed predilections exist. 
• May be secondary to other corneal 
diseases with breed predispositions and 
genetic basis, such as corneal epithelial 
dystrophy in Shetland sheepdogs and 
corneal endothelial dystrophy in Boston 
terriers.
Common
Species
• Dogs—brachycephalic breeds predisposed. 
• Spontaneous chronic corneal epithelial 
defects (SCCED)/indolent erosion—any 
breed. •  Cats—Persian, Himalayans, Siamese, 
and Burmese predisposed to corneal seques -
trums (see Corneal Sequestrum—Cats).
• Age of onset—variable; determined by cause. 
• SCCED—middle-aged and older dogs.
SIGNS
• May be acute or chronic (SCCED). 
• Tearing, squinting, rubbing at eyes. 
• Owners may report a “film” over the eye 
(often corneal edema); prolapsed third eyelid. 
• Herpetic ulcers (cats)—may have history of 
• Nonspecific—serous to mucopurulent ocular 
discharge, blepharospasm, nictitans prolapse, 
conjunctival hyperemia. •  Superficial—may 
note one or more circumscribed, linear, or 
geographic defects in cornea. •  Deep stromal 
ulcer or descemetocele—may appear as a 
crater-like defect. •  Depending on cause and 
duration—may see neovascularization, 
pigmentation, scarring, inflammatory cell 
infiltrate (yellow to cream-colored opacity 
with indistinct margins, often surrounded by 
corneal edema), collagenolytic activity 
(melting) of corneal stroma. •  SCCED—
loose or redundant epithelial edges; may 
demonstrate fluorescein stain extending into 
areas with seemingly intact epithelium (ring 
of less intense staining). •  Reflex anterior 
uveitis—mild or severe, secondary to 
ulceration; severe may result in hypopyon; 
severe suggests concurrent bacterial infection.
CAUSES
• T rauma—blunt; penetrating; perforating. 
• Adnexal disease—ectopic cilia, entropion, 
ectropion, eyelid mass, distichiasis. 
• Lagophthalmos (inability to close eyelids 
completely)—results in exposure keratitis; 
may be breed-related in brachycephalic dogs 
and cats; may be caused by exophthalmos, 
buphthalmos, or may be neuroparalytic from 
facial nerve paralysis. •  Tear-film abnormality—
quantitative tear deficiency (keratoconjuncti-
vitis sicca [KCS]); qualitative tear film 
deficiency caused by mucin deficiency or 
some other unidentified tear abnormality. 
• Infection—usually secondary in dogs; can 
be primary herpesvirus infection in cats. 
• Primary corneal disease—endothelial 
dystrophy; other endothelial disease. 
• Miscellaneous—foreign body (corneal or 
conjunctival), chemical burns, neurotrophic 
keratitis (loss of trigeminal sensation), 
immune-mediated disease.  DIAGNOSIS
• Other causes of a red and painful eye—
conjunctivitis, uveitis, KCS, glaucoma 
(see Red Eye). •  May develop concurrently 
with other causes of a red eye (e.g., secondary 
to KCS).
• Corneal culture and sensitivity—aerobic 
culture; particularly for complicated, deep, or 
rapidly progressive corneal ulcers. 
• Herpesvirus (cats)—PCR or immuno -
fluorescent antibody test (IFA) for herpesvirus 
available; negative test does not rule out 
herpesvirus infection.
Fluorescein Staining
• Homogeneous stain uptake—superficial 
or stromal ulcer; may be circular to 
geographic, linear, or combination; location 
and shape may help determine cause (e.g., 
linear may indicate foreign body or rubbing 
of ectopic cilia); interpretation of depth 
subjective. •  SCCED—may have leakage of 
stain under surrounding loose epithelium. 
• Descemetocele—crater-like defect that 
retains stain at periphery but is clear at 
center; may see Descemet’s membrane 
bulging if large defect. •  Previous stromal 
ulcer that has epithelialized (facet)—crater-
like defect with transient pooling of stain 
that is easily rinsed; must distinguish from 
descemetocele.
Other
• Cytologic evaluation of cornea and Gram, 
Giemsa, or Wright staining may reveal 
microbial or fungal organisms and help direct 
initial antimicrobial therapy. •  Schirmer tear 
test may identify ulceration associated with 
KCS; contraindicated in very deep ulcers or 
descemetoceles.
• Ulcers—suppurative inflammation, 
possibly neovascularization, loss of epithelium 
and basement membrane; possibly organisms. 
• SCCEDs—superficial hylanized zone in 
stroma; epithelial lipping around erosions; 
varying degrees and types of leukocytic 
infiltrate and fibrosis.
  TREATMENT
Hospitalize deep or rapidly progressive ulcers; 
these may require surgery and/or frequent 
medical treatments.

Canine and Feline, Seventh Edition  799
KNURSING CARE
Keep facial hair out of eyes and clean.
ACTIVITY
• Restrict with deep stromal ulcer or 
descemetocele to prevent rupture. •  Prevent 
self-trauma with Elizabethan collar.
• Instruct client to wait at least 5 minutes 
between medications if more than one 
ophthalmic drop is prescribed; wait longer 
between ointments. •  Advise client to contact 
veterinarian if patient appears more painful or 
the eye markedly changes in appearance. 
• SCCED—discuss protracted course with 
client; usually achieve healing within 2–6 
weeks but may require weekly rechecks and 
multiple procedures.
• Superficial ulcers do not usually require 
surgery if inciting cause has been eliminated. 
• Ulcer that extends one-half or greater corneal 
thickness and particularly to Descemet’s 
membrane may benefit from surgery. 
• Descemetocele or full-thickness corneal 
laceration—surgical emergency, possible referral.
Procedures
• SCCED—debridement of loose epithelium 
with a dry, sterile, cotton-tipped swab after 
application of topical anesthesia (50% success 
rate); punctate or grid keratotomy easily 
performed after epithelial debridement with 
topical anesthesia (80% success rate); superficial 
keratectomy is more invasive and may cause 
more scarring but has 100% success rate; 
application of a contact lens or nictitans flap 
after any of these procedures may improve 
comfort and aid healing. •  Diamond burr 
keratotomy for SCCED/indolent erosion only; 
use gently over surface of erosion; may be 
associated with increased risk of infection. 
• Rotational pedicle conjunctival flap, 
corneoscleral transposition, corneal transplant—
surgical procedures for ulcers >50% stromal 
thickness and descemetoceles. •  Cyanoacrylate 
repair (corneal glue)—can be used for deep 
ulcers; promotes corneal vascularization and 
stabilizes cornea, but has lower success rate 
compared to other corneal surgeries.
• Topical agents—indicated for all patients. 
• Frequency of application—determined by 
severity and preparation; ointments have 
relatively long contact time and are applied 
q6–12h; solutions are applied more frequently (q2–6h) in initial treatment of 
complicated ulcers; solutions probably more 
appropriate in deep ulcers. •  Commonly 
used agents—erythromycin (cats); triple 
antibiotic, gentamicin, and tobramycin. 
• Uncomplicated ulcers or superficial 
erosions—combination of neomycin, 
polymyxin B, and bacitracin an excellent 
first choice; broad spectrum of antimicrobial 
activity; often used 2–3 times/day for 
prophylactic therapy. •  Complicated 
ulcers—often use combination therapy of 
cefazolin (use IV solution to make 
33–50 mg solution in saline or artificial tears 
for topical use) with a fluoroquinolone 
(ciprofloxacin, ofloxacin); particularly in 
rapidly progressive, deep, or melting ulcers; 
frequency depends on severity but usually a 
minimum of q3–4h.
Atropine
• 1% ointment or solution. •  Indicated for 
reflex anterior uveitis; frequency—usually 
q8–24h to effect (mydriasis).
Antiviral Agents
• Indicated for herpetic ulcers in cats. 
• T rifluridine (Viroptic) solution—q4–6h 
until clinical response is observed; then 
reduce for 1–2 weeks after clinical signs have 
subsided. •  Famciclovir—90 mg/kg PO q12h 
for 2–4 weeks.
(NSAIDs)
• Flurbiprofen, diclofenac. •  For anti-
inflammatory and analgesic properties.
• Topical corticosteroids—contraindicated 
with any corneal erosion or ulcer. •  Topical 
NSAIDs—contraindicated with herpetic 
ulcers. •  Topical atropine—contraindicated 
with glaucoma, KCS.
• Topical NSAIDs may delay corneal 
healing, may potentiate corneal melting. 
• T rifluridine, neomycin—may be 
irritating. •  Topical cyclosporine can be 
used safely in KCS patients with 
uncomplicated ulcers.
Combining antibiotics in solution may 
inactivate some antibiotics.
• Acetylcysteine—anticollagenolytic agent 
used for treatment of melting ulcers; efficacy 
is controversial; dilute 20% stock solution to 
5–10% with artificial tears; apply q2–4h. 
• Serum—anticollagenolytic agent; keep 
refrigerated; avoid contamination; discard 
after 48 hours.  FOLLOW-UP
• Superficial ulcers—repeat fluorescein stain in 
3–6 days; if it persists 7 days or longer, either 
inciting cause has not been eliminated or patient 
has an SCCED. •  Deep stromal or rapidly 
progressive ulcers—assess every 24 hours 
initially if outpatient until improvement is seen; 
many of these patients are hospitalized or 
undergo surgery; decrease frequency of 
antibiotic therapy as condition improves.
• Brachycephalic dogs—lubricant ointment 
administration, permanent partial tarsorrhaphy 
surgery, or both may prevent recurrent 
ulceration. •  KCS-related ulcers—lifelong 
treatment of KCS (cyclosporine) or parotid 
duct transposition surgery. •  Herpesvirus 
(cats)—oral lysine (250 mg PO q12h) may 
prevent viral replication; may decrease severity 
and/or frequency of outbreaks.
Progressive corneal ulceration—rupture of 
globe, endophthalmitis, secondary glaucoma, 
phthisis bulbi, blindness, blind and painful 
eye (may require enucleation).
PROGNOSIS
• Uncomplicated superficial ulcer—usually 
heals in 5–7 days. •  SCCED—may persist for 
weeks to months; may require multiple 
procedures. •  Deep corneal ulcer treated 
medically—may require several weeks for 
fibrovascular repair of defect; does not always 
granulate satisfactorily; continued deteriora -
tion of ulcer and globe rupture are possible. 
• Deep ulcer treated with conjunctival flap—
frequently results in more comfort within a 
few days after surgery; blood supply to flap 
can be cut in 4–6 weeks to decrease scarring.
• IFA = immunofluorescent antibody test.
drug.
• SCCED = spontaneous chronic corneal 
epithelial defect.
available online(continued)  Keratitis, Ulcerative

800  Blackwell’s Five-Minute Veterinary Consult  
KKeratoconjunctivitis Sicca
  BASICS
OVERVIEW
• Deficiency of the aqueous layer of 
precorneal tear film.
• Causes corneal/conjunctival drying and 
resultant surface inflammation.
• Common in dog; rare in cat.
• Predisposed dog breeds—many brachycephalic 
and spaniel breeds, miniature schnauzers, 
poodles, bloodhounds, Samoyeds, West 
Highland white terriers, and Yorkshire terriers.
• Inheritance—undefined.
• Age of onset—variable and depends on 
inciting cause.
SIGNS
• Conjunctival hyperemia.
• Mucoid to mucopurulent ocular 
discharge—intermittent to persistent 
depending on severity.
• Corneal changes—dryness, superficial 
vascularization, pigmentation, fibrosis, ulceration.
• Blepharitis due to ocular exudates.
• Severe disease—impaired vision or blindness.
• Cats are less symptomatic than dogs.
• Immune-mediated/idiopathic—most 
common, possibly associated with other 
immune-mediated diseases (e.g., atopy).
• Infectious—canine distemper virus; 
leishmaniasis; chronic blepharoconjunctivitis 
(e.g., feline herpesvirus).
• Iatrogenic—removal of third eyelid gland 
(especially in at-risk breeds), radiation therapy.
• Congenital—Yorkshire terriers overrepresented.
• Neurologic—loss of parasympathetic 
innervation to lacrimal gland, trigeminal nerve 
deficit, or dysautonomia; neurogenic parasym -
pathetic loss may have ipsilateral dry nose.
• T raumatic—after ocular proptosis or orbit 
• Systemic disease—diabetes mellitus, hyper -
adrenocorticism, hypothyroidism, or any 
debilitating disease.
• Drug-induced—systemic sulfonamides 
(e.g., trimethoprim-sulfadiazine).
• T ransient—general anesthesia and atropine.
  DIAGNOSIS
• Often confused with allergic or bacterial 
• Dogs with keratoconjunctivitis sicca (KCS) 
may have concurrent bacterial overgrowth.
• Differentiate with Schirmer tear test.DIAGNOSTIC PROCEDURES
• Schirmer tear test—normal value at least 
9 mm/min (cat) or 15 mm/min (dog) of 
wetting; symptomatic patients usually 
<10 mm/min of wetting; lower values 
combined with clinical signs suggest KCS.
• Fluorescein staining—may show corneal 
ulcers.
• Conjunctival cytology—may demonstrate 
bacterial overgrowth.
 TREATMENT
• Outpatient—unless severe corneal 
• Instruct client to use solution(s) before 
• Advise client to call at once if ocular pain 
increases (patients are predisposed to corneal 
• Parotid duct transposition—surgical option 
for dogs and cats that reroutes parotid duct to 
deliver saliva to ocular surface if KCS is 
refractory to lacrimostimulant therapy.
◦ More common with congenital KCS.
◦ Saliva can irritate cornea and result in 
mineral deposits; some patients require 
ongoing topical therapy.
• Episcleral cyclosporine implant—for dogs 
responsive to topical cyclosporine but with 
poor owner compliance.
• Lacrimostimulants—cyclosporine 0.2% 
ointment or 1–2% solution; tacrolimus 
0.02–0.03% solution or ointment—therapy 
q12h recommended (q8h if severe or 
refractory).
• For neurogenic KCS—pilocarpine 
0.1–0.2% topically q8h or very careful oral 
pilocarpine (narrow therapeutic window; see 
Suggested Reading).
• For feline KCS—antiviral therapy (see 
Conjunctivitis—Cats); hyaluronate-based 
artificial tear in short term; consider 
lacrimostimulant therapy.
• Lacrimomimetics—artificial tears to 
moisten ocular surface to improve comfort; 
use viscous solutions or gels q2–12h 
depending on severity and ointment before 
bedtime; can reduce frequency once patient 
responds to lacrimostimulants.
• Broad-spectrum antibiotics—topical 
ointment q6–8h for 3–4 weeks; indicated for 
secondary bacterial overgrowth or concurrent 
corneal ulceration.• Ocular cleansing—use eye wash to remove 
discharge and debris prior to administering 
medications; if mucoid discharge is very 
tenacious, 5% N-acetylcysteine can be used 
q6–12h as a mucinolytic agent prior to eye 
rinsing.
• Corticosteroids—topical; minimize 
inflammation; can reduce corneal vasculari -
zation and pigmentation once aqueous tears 
improve; not commonly used (corneal ulcer 
risk).
• Topical cyclosporine or tacrolimus—rarely 
irritating, but if noted consider compounded 
aqueous preparation.
• Pilocarpine—initially irritating topically; 
systemic side effect risk.
• Topical corticosteroids—avoid with 
ulcerative keratitis or severe KCS (corneal 
ulcer risk).
  FOLLOW-UP
• Regular rechecks—monitor response and 
progress.
• Schirmer tear test—4–6 weeks after 
initiating cyclosporine or tacrolimus (patient 
should receive drug as prescribed on day of 
visit).
• Usually requires life-long treatment.
• Good prognosis but refractory cases may 
require more aggressive therapy (e.g., up to 
1% tacrolimus) or surgery (e.g., parotid duct 
transposition).
• KCS = keratoconjunctivitis sicca.
Maggs DJ, Miller PE, Ofri R. Diseases of 
the lacrimal system. In: Slatter’s 
Elsevier, 2018, pp. 186–212.

Canine and Feline, Seventh Edition  801
KKitten Behavior Problems
  BASICS
Undesirable behaviors exhibited by kittens 
between birth and puberty.
• Most pediatric behavior problems are normal, 
species-typical behaviors. • Lack of appropriate 
social interactions and environmental stimula -
tion and genetics can contribute to abnormal or 
unwanted behaviors.
GENETICS
Paternal influences on friendliness to people 
and boldness to unfamiliar or novel objects 
have been supported.
Species
Cats
Generally 6–48 weeks.
SIGNS
Play Aggression
• Elements of predation including stalking, 
chasing, attacking, pouncing, swatting, and 
biting. Play can be solitary, with objects, or 
social to another kitten, animal or person.  
• With normal play, bites are inhibited and 
claws retracted. Vocalizations are rare compared 
to other forms of feline aggression.  
• Inappropriate play behaviors may be 
uninhibited, leading to bite and scratch injuries.
Excessive Play/Activity and/or Destructive 
Play
High level of solitary play (running, jumping, 
climbing, object play) may result in house-
hold damage and disruption.
Scratching
• Use of claws to scratch on household items 
and/or people.
• Scratching is a normal behavior for claw 
maintenance, territorial marking, and defense 
but becomes problematic when scratched 
objects include walls, furniture, carpets, and 
other household items.
Fearful Behaviors
Includes hiding, hissing, scratching, and unsocial 
behaviors and can include varying manifestations 
of aggression to another animal or person.
Aggressive Play Directed toward People or 
Other Pets in the Household
• Attacks directed toward people or other 
pets in the household. • Ambushes are 
common and lack vocalizations. Bites are 
generally inhibited but may puncture the skin 
and light scratches with claws may occur. Can 
be more serious in the elderly owner.Uninhibited Aggressive Play Directed 
toward People
• Signs similar to above except more intense. 
• Bites and scratches are not as inhibited and 
can break skin.
Play Directed toward Household Objects
• Bursts of solitary play that include intense 
running, climbing across and up household 
furnishings. • Knocks or swipes objects 
from surfaces.
Household items and family members.
Fear and Defensive Behaviors Due to Lack 
of Socialization
• Insufficient exposure to people before 7–9 
weeks of age.  • Behaviors associated with fear, 
e.g., dilated pupils, piloerection, defensive 
postures, hissing, hiding, fleeing, aggression.
Fear and Defensive Behaviors Related 
to Early Trauma
Normal until experience traumatic event, e.g., 
abuse, attack by another animal.
to Correction T echniques
• History of punishment by owner(s). 
• Kitten shows defensive postures including 
hissing, fleeing, hiding, dilated pupils, 
piloerection in presence of owner or in 
response to corrections.
CAUSES
Aggressive Play Directed toward People 
or Other Cats in the Household
• Normal species-typical behavior but 
without appropriate social interaction with 
conspecifics, the behavior can become 
uninhibited and injurious.  • Owners may 
encourage inappropriate interactive play by 
promoting play with human body parts 
(fingers, hands, feet).  • Lack of outlets for 
Play Directed toward Objects 
in the Household
Normal species-typical behavior beginning at 
7–8 weeks of age.
Fear and Defensive Behaviors 
Due to Lack of Early Socialization
No or minimal amount of exposure to people 
before 7–9 weeks of age.
Early traumatic event.
to Correction Techniques
Normal until “corrected” by person, e.g., 
spanked, swatted, flicked on nose, yelled at, 
chased.
Aggressive Play Directed toward People
• Only cat in household, hand-reared kitten, or 
adoption prior to 6 weeks of age.  • Insufficient appropriate outlets for normal play and 
exploration.  • Encouragement of inappropriate 
play (e.g., with hands, fingers, feet).
• Lack of sufficient/appropriate enrichment 
including toys and interactive play with people 
or other animals. • Only pet in household.
Lack of appropriate/inadequate scratching outlets.
Fear and Defensive Behaviors
• Lack of appropriate socialization with people, 
use of punishment and other traumatic 
experience(s). • Removing kittens less than 2 
weeks of age from queen may result in fearful and 
aggressive kittens towards humans and other cats.
  DIAGNOSIS
Play Aggression toward People
Differentiate normal play from the more 
serious, uninhibited play aggression.
Excessive Play/Destructive Behaviors
None.
Nail maintenance, marking, play-related, or 
defense.
Fearful and Defensive Behaviors
CNS diseases, pain, metabolic disorders, pain.
Frightened kittens may have elevated glucose 
levels, stress leukogram.
  TREATMENT
ACTIVITY
Many kitten behavior problems can be 
alleviated or reduced by enriching kitten’s 
environment (e.g., provide movable toys, variety 
of toys, rotating them regularly). Engage the 
kitten in interactive play directed away from the 
owner’s body parts. Provide access to window 
sills and perches. Offer a variety of enticing 
scratching surfaces. Possibly get second kitten.
DIET
Provide multiple small meals. Use food 
delivery toys.
Most of these problems are normal kitten 
behaviors that owners perceive as abnormal or 
excessive and inappropriate for their lifestyle. 
Most kittens will mature out of these problem 
behaviors with appropriate management and 
by providing for behavioral needs.
• Owner needs to initiate regular interactive 
play that allows for hunt, stalk and attack 
behaviors directed at appropriate toys or objects.

802  Blackwell’s Five-Minute Veterinary Consult  
KEnsure owners never use hands, fingers, or feet 
to encourage play.  • Effective treatment may be 
to acquire another kitten, if size and 
temperament are compatible.  • Redirection: 
Identify situations in which the attacks may 
occur. Watch for signs of dilated pupils, stalking, 
crouching, tail swishing. Be prepared to redirect 
the play to another object (e.g., tossing a 
wadded piece of paper or chasing a toy) or to 
cue and reward alternative desirable behaviors 
that the kitten has learned (e.g., go to mat, sit/
watch, let’s eat, let’s play).  • Educate the client 
to not hit or swat or punish.  • Immediately 
stop any attention or play for inappropriate 
behaviors.  • Interrupt to redirect into 
alternative acceptable behaviors with trained 
cues (sit, go to mat) or with a noise to reorient 
into desirable play.  • Frequent trimming of 
claws helps reduce damage caused by nails.  
• For humane and welfare reasons declawing 
is strongly discouraged and prohibited in 
many countries and jurisdictions. Where 
legally permissible it should be a last resort 
only if owners have been fully counselled on 
behavior management, modification and 
alternative options. 
Aggressive Play Directed toward Other 
Cats in the Household
• Acquire additional kitten of the same size and 
temperament as the problem kitten.  • Watch 
for signs and redirect into alternative acceptable 
behaviors (sit/watch, go to mat).  • Problem 
kitten and other cat should have restricted access 
to each other at times when problems might 
arise.  • Startling, punitive techniques may 
aversively affect the other cat and are not 
recommended.  • Provide appropriate outlets 
for predatory behaviors with the problem kitten 
on a regular, daily basis using toys or objects.
Play That Is Excessive and/or 
Destructive, and Scratching
• Put valuable, breakable, or dangerous objects 
away.  • Provide a variety of appropriate toys for 
batting and food delivery and rotate every few 
days to maintain novelty and interest.  
• Interactive play with kitten using toys or objects 
on a daily basis.  • Provide scratching posts using 
materials that are cat’s preferred substrates and 
assure they are long enough and stable enough 
for the cat to stretch and scratch.  • Place 
scratching stations in commonly used areas and 
encourage use with catnip, treats, and integrating 
perches and resting areas.  • Decrease the appeal 
of the targeted objects, e.g., with sticky tape, 
unpleasant taste or odor, or less appealing 
substrate.  • Frequent trimming of claws.  
• Declawing is a humane concern and in many 
places prohibited.  
Due to Lack of Early Socialization or 
from Early Trauma
• Gradual exposure to people without forcing 
interactions, provided no negative outcome/
endpoint.  • House kitten where it is 
comfortable, where it can remove itself from 
view but be aware of people.  • Counter-conditioning generally required. Highly enticing 
food and treats should be offered. Initially, food 
can be put in or near hiding area. Gradually food 
is given with increasing proximity to the people, 
ending each session at a distance or location 
where the cat remains calm and will take food. 
No attempt should be made to grab or hold the 
kitten. Progress gradually until the kitten takes 
food that is tossed toward it, given by hand, 
or given while the kitten is on the person’s lap. 
Counter-conditioning can also include play with 
toys that can tossed or chased, such as those on 
wands or ropes.  • Important: Let the kitten 
make the advances—not the person—and avoid 
any fearful endpoint by forcing interaction, 
preventing escape, or progressing too quickly.
Identify and cease inappropriate punishment.
• None needed except as indicated for fear 
and anxiety. See also Fears, Phobias, and 
Anxieties—Cats. • May consider use of feline 
pheromones and nutritional supplements 
with alpha-casozepine or l-theanine for mild 
fear and anxiety.
  FOLLOW-UP
• Telephone follow-up support is helpful.
• Be sure clients are not using aversive 
techniques that may induce fear and 
aggression in the kitten and/or exacerbate 
intensity of play aggression.
• Kitten behavior problems are often a result 
of owner’s unrealistic expectations and 
misunderstanding of normal kitten behavior, 
as well as lack of enrichment and appropriate 
predatory play outlets.  • Between 3 and 7 
weeks of age, kittens should experience positive 
interactions with people to reduce fear and 
develop appropriate social bonds with humans.  
• Between 4 and 18 weeks, it is helpful to have 
exposure to tolerant (and playful) conspecifics 
to learn effective bite and play inhibition.  
• Advise family members to avoid rough -
housing and body part play with kittens.
• Discourage punitive corrections.
Normal Play Behaviors Directed toward 
People, Other Cats, and Household 
Objects
Reduction or resolution of problem when 
appropriate treatment protocols are followed. 
Many behaviors may begin to wane with 
maturity.Uninhibited Aggressive Play Directed 
• Guarded prognosis. • Aggression may 
become more severe with maturity. A better 
prognosis is given to those cases that are 
caught early and appropriately counseled or 
by obtaining a second compatible cat.
If measures to prevent, divert, and reward for 
using appropriate scratching surfaces are 
successful, the prognosis is good, and as the 
kitten matures, the behaviors wane. Some cats 
may need long-term management.
Related to Early Trauma
Kittens vary in the degree to which they 
acclimate to people; improvement may take 
months to years; some may never be 
comfortable around people.
• The longer the interval from 3 weeks of age 
to exposure to people, the poorer the prognosis.  
• The more intense the early trauma, the 
poorer the prognosis.
These can resolve if corrections have not been 
too frequent or too intense, and the clients 
follow advice to replace these techniques with 
reward-based, avoidance, and redirection 
During the sensitive period, between 3 and 7 
weeks, the kitten must be exposed to people 
to prevent fearful and defensive responses to 
them.
• https://indoorpet.osu.edu/cats  • https://
catvets.com/guidelines/practice-guidelines—
environmental needs, lifestyle, enrichment
Bradshaw J, Ellis S. The T rainable Cat—A 
You and Your Cat. New York, NY: Basic 
Books, 2016.
Herron ME, Horwitz D, Siracusa C, et al. 
Decoding your cat: The ultimate experts 
explain common cat behaviors and reveal how 
to prevent or change unwanted ones. New 
York, Houghton Mifflin Harcourt, 2020.
Author  Kelly Moffat
available onlineKitten Behavior Problems  (continued)

Canine and Feline, Seventh Edition  803
KKitten Socialization and Kitten Classes
  BASICS
OVERVIEW
• Early experiences set the foundation for 
future behavior, having long lasting effects on 
social behavior, temperament, and the ability 
to learn and relate to various stimuli and to 
cope in various environmental contexts. 
• For a kitten to grow up into a well-adjusted 
adult cat, adequate socialization and 
environmental exposure is needed during the 
socialization period and beyond into the first 
year of life.
Definitions
• Socialization—a process of learning normal 
behavior, communication, and social skills for 
appropriate interactions with other individuals 
in various contexts. •  Socialization period—a 
sensitive window of development whereby a 
cat learns to communicate and relate to other 
cats, humans, and the environment. •  Kitten 
classes—also called kitten “kindy” or 
kindergarten. Allow cats to socialize with 
other cats, a variety of people, and to be 
exposed to multiple and varied environmental 
stimuli in a positive and nonthreatening 
manner.
Potential effects on behavioral and 
neurological development.
Genetics
Genetics or the paternity of the kittens, with 
kittens sired from friendly toms being 
friendlier toward people.
Mean Age
• The sensitive socialization period is between 
2 weeks and 7 weeks, yet socialization is a 
continuous process. During the socialization 
period, less experience is necessary to produce 
profound effects on future behavior. Handling 
only 15 minutes per day from 2 to 6 weeks of 
age has been shown to produce more friendly 
kittens. •  For kitten classes—healthy 
dewormed kittens should begin attending 
group classes 10 days after receiving the first 
vaccination of their kitten immunization 
series. Typically begin classes between 8 and 
12 weeks and conclude by 14 weeks.
• Male kittens play more with objects than 
females. •  No sex differences in social play.
SIGNS
• Lack of adequate socialization experiences 
during sensitive periods of development. 
• Cat-directed fear and/or aggression—lack 
of early familiarity and positive exposure with 
other cats. •  Human-directed fear and/or 
aggression—early positive social experiences with humans prior to 7 weeks, otherwise fear, 
avoidance, aggression, and behaving as if 
“feral.” •  Predatory aggression—exposure to 
future prey species, starting at 4 weeks, can 
improve predatory behavior and hunting 
ability, whereas exposure to non-prey species 
may reduce aggression later in life. •  Fear and 
anxiety in unfamiliar environments. 
• Attendance at group kitten classes at an 
early age can prevent future behavior 
problems and/or allow for the early 
identification of abnormal and problematic 
behavior. •  Kitten classes—age-specific (8 
and 12 weeks at start and finished by 14 
weeks) for group-controlled interactions. 
Focus is education regarding normal behavior, 
the prevention of behavior problems, and 
addressing normal problematic behaviors 
through management, supervision, and 
positive reinforcement training.
• Avoiding environmental and social 
experiences prior to the completion of kitten 
vaccination series increases the risk of future 
behavior problems. •  The risk of exposure to 
infectious disease with socialization and 
environmental exposure needs to be 
considered along with the risk of being 
undersocialized and not suitable as a pet 
because of lifelong fear, anxiety, and aggressive 
issues. •  A clean bill of health and initial 
vaccinations must have been administered at 
least 10 days prior to class. •  Kittens should 
be dewormed according to the Companion 
Animal Parasite Council guidelines. https://
capcvet.org/guidelines/general-guidelines/ 
• Kittens should be screened for contagious 
diseases, such as upper respiratory infection 
and ringworm, prior to each class. •  Kitten 
classes “vaccinate” the kitten against behavior 
problems later in life. •  Genetics and a lack 
of socialization can render some kittens 
intolerant to human handling and behaving 
as if feral. •  Kittens removed from the queen 
and exclusively hand raised by humans are 
more fearful and aggressive toward cats and 
humans, tend to be hyperactive, have 
difficulty forming social attachments with 
other cats, and display poor learning ability. 
• Removal from the queen and littermates 
prior to 10 weeks of age may increase the risk 
of inter-cat aggression with a lack of learned 
social skills. •  Kittens weaned too early are 
more likely to perform non-nutritive suckling 
and kneading of objects. •  Experiences at the 
veterinary clinic should employ Fear Free 
and/or Low Stress handling techniques. 
• T raumatic experiences that induce fear 
during sensitive fear periods when the kitten 
is between 6 and 8 weeks of age should be 
avoided. •  Avoiding exposure to other species 
during socialization may result in fear toward 
the species, whereas experience with species 
that might normally have a predator–prey relationship may increase predatory behavior 
toward that species. •  Early exposure of 
kittens to dogs living within the household 
improves the likelihood of successful 
cohabitation. •  Kitten socialization with 
people and cats is only beneficial to 
behavioral development if the kitten finds 
human and/or cat contact enjoyable. 
Continued exposure when it induces fear is 
unlikely to result in habituation to the 
stimulus and is likely to exacerbate fear and/
or aggression.
  DIAGNOSIS
Identify abnormal and/or problematic 
behavior and make a behavioral diagnosis or 
schedule or refer for a behavior consultation.
Possible Behavioral Manifestations 
of a Lack of Socialization
• Global fears, encompassing fears of people, 
cats, other animals, objects, sounds, and 
environments. •  Generalized anxiety and 
situational anxiety in unfamiliar environments. 
• Specific fears, neophobia and failure to 
habituate to novelty or stimuli. •  Noise 
sensitivity, aversions, and phobias. 
• Hyperexcitability and hypervigilance with an 
inability to settle due to a lack of early 
environmental enrichment. •  Aggression 
toward people and cats in various contexts with 
various motivations (e.g., fear, predatory).
  TREATMENT
Recommendations for Socialization
• Socialization “vaccinates” the kitten against 
the development of future behavioral 
problems and should begin concurrently with 
the kitten immunization series. •  Food treats 
and social play should be used liberally with 
new and repeated kitten socialization 
experiences while keeping the kitten safe. 
• Social play and exploration should be 
encouraged using toys in various contexts and 
environments while keeping the kitten safe. 
• Healthy kittens usually have good 
appetites. If the kitten is not consuming food 
treats in specific contexts, it suggests the 
kitten is fearful and the experience is not 
positive or beneficial for socialization. 
• Healthy and well-adjusted kittens play. If 
the kitten will not engage in play, it suggests 
the kitten is fearful and the experience is not 
• Socialization by the breeder—gentle 
handling should occur daily, shortly after 
birth, and include exposure to multiple

804  Blackwell’s Five-Minute Veterinary Consult  
Kpeople, various smells and different surfaces 
with mild fluctuations in temperature. 
• Socialization at the owner’s home—allow 
the kitten to choose to interact and make 
exposure positive with the liberal use of food 
treats. Meet people of different ages, stature, 
gait and complexion. Meet other pets to 
potentially prevent fear and aggression. 
• Attendance at group kitten classes and 
social exposure is recommended for all 
healthy kittens prior to 14 weeks of age and 
prior to being fully vaccinated.
Recommendations for Kitten Classes
• All healthy kittens between 8 and 12 
weeks should be enrolled into group classes. 
• Kittens attending are deemed healthy by a 
veterinary examination, have been 
dewormed, and have started their 
vaccination series. The first class might be 
attended by owners only, particularly if 
scheduled to begin within the first 10 days 
after vaccination. •  Group classes are often 
held at veterinary clinics, allowing for 
positive interactions with other kittens, 
people, and objects. •  Classes are attended 
by kittens and their owners at least weekly 
and are typically about an hour in length. 
• Rotating classes cover the following 
topics: ◦ Play sessions—controlled and 
monitored play (5–10 minutes) with other 
kittens in a secure environment, typically at 
the start and end of class. ◦ Health and 
handling—instruction and positive 
handling for routine health and grooming 
procedures in the veterinary clinic, at the 
grooming facility, and at home. ◦ Sights 
and sounds—exposure to novel 
environments, objects, surfaces, and sounds 
in a positive and fun manner. Various 
people attending interact with kittens in a 
positive manner. ◦ Rearing advice—
education on normal cat body language, 
learning, behavior problem solving and 
prevention, and kitten rearing. ◦ Basic 
manners—positive reinforcement training 
to address mouthing/biting/scratching, 
jumping on furniture/counters, chewing 
and scratching objects, stealing objects, 
carrier, collar/harness/leash, and litterbox 
training. ◦ Kitten classes offered at the 
veterinary hospital can also insure a focus 
on positive exposures to the veterinary 
facility, equipment, and procedures.  MEDICATIONS
• A selective serotonin reuptake inhibitor or 
tricyclic antidepressant may be indicated for 
fear, anxiety, and aggression-related problems 
when combined with behavior and 
environmental modification for the specific 
diagnosis. •  May “in effect” chemically place 
the kitten back into its socialization state and 
aid socialization. •  Consider daily or 
situational behavior medications for cats 12 
weeks of age or greater who demonstrate 
abnormal fear, anxiety, or aggression.
Nutraceuticals/Supplements
• Alpha-casozepine, a bovine-sourced 
hydrolyzed milk protein, may have calming 
properties. •  l-Theanine, an extract of green 
tea, may reduce fear, anxiety, and stress.
• Feliway Classic (CEVA), a synthetic cheek 
gland pheromone, may have calming 
properties and facilitate adaptation to new 
environments. •  Feliway Multicat (CEVA), 
a synthetic mammary pheromone, can 
mediate social tension between cats. 
• FeliScratch (CEVA), a synthetic 
interdigital pheromone, may promote 
scratching in specific locations.
Avoid selective serotonin reuptake inhibitors 
and tricyclic antidepressants in combination 
and use with caution with other serotonin-
influencing drugs.
  FOLLOW-UP
Kitten owners should be questioned during 
routine heath examinations and encouraged 
to bring concerns regarding problematic 
behavior to their veterinarian’s attention as 
soon as the problem is identified.
• Prevention of problems is preferable and easier 
than treatment. •  Socialization experiences must be positive for the kitten to benefit from those 
experiences. •  Avoid exposure which induces 
negative emotions as it is difficult to habituate to 
stimuli that induce fear, anxiety, and stress. 
• Preventive counseling at the first kitten visit 
reduces the risk of undesirable climbing on 
furniture and curtains, undesirable vocalization, 
and increases amenability to body handling.
• Kittens obtained after their socialization 
period with little prior socialization and those 
that have been raised in suboptimal 
environments may be resistant to socialization. 
• Unwillingness to consume treats, explore, 
and/or play in socialization contexts suggest 
that the exposure is not positive for the kitten.
Early identification and intervention gives the 
best prognostic outcome and chance for cure.
Behavioral conditions associated with fear, 
anxiety, and aggression contexts.
• www.stevedalepetworld.com/blog/kitty-k/ 
• dacvb.org •  catvets.com •  indoorpet.osu.
edu/cats
Herron, M. E., Horwitz, D., Siracusa, C., 
&amp; Dale, S. (2020). Decoding your cat: 
The ultimate experts explain common cat 
Houpt, K. Domestic Animal Behavior for 
Veterinarians and Animal Scientists, 6th ed. 
Hoboken, NJ: John Wiley & Sons, 2018.
Shaw, JK, Martin D. Canine and Feline 
Behavior for Veterinary Technicians and 
Nurses. Ames, IA: John Wiley & Sons, 
2015.
Authors  Kenneth M. Martin and Debbie Martin
Consulting Editor  Gary M. LandsbergKitten Socialization and Kitten Classes  (continued)

Canine and Feline, Seventh Edition  805
LLactic Acidosis (Hyperlactatemia)
  BASICS
• Blood lactate concentration >1.5 mmol/L 
in dogs and >1.8 mmol/L in cats.
• Lactic acidosis is hyperlactatemia with 
concurrent metabolic acidosis.
• Plasma lactate is a late but quantitative 
indicator of tissue hypoperfusion. Hypo­
perfusion and tissue hypoxia occur before a 
rise in blood lactate is detectable.
• Lactic acid is the end product of 
anaerobic glucose metabolism; at 
physiologic pH, lactic acid immediately 
dissociates to lactate and hydrogen ions. 
Clinically significant lactate accumulation 
can be due to anaerobic glycolysis occurring 
during normal physiologic (e.g., exercise) or 
pathologic processes (e.g., shock, seizures).
• Lactate exists as levorotatory (l ­lactate) and 
dextrorotatory (d ­lactate) stereoisomers. 
l­Lactate predominates in mammalian cells 
and is the only form detectable by routine 
analysis.
• Hepatic and renal lactate metabolism 
maintains a balance between lactate 
production and clearance.
• In most critically ill or injured patients, 
hyperlactatemia and lactic acidosis are due to 
conditions that cause tissue hypoxia, with a 
shift to anaerobic glycolysis.
• Inadequate perfusion, severe hypoxemia, 
increased oxygen demand, decreased 
hemoglobin concentration, or combinations 
of these factors can cause tissue hypoxia.
• Clinically evident tissue hypoperfusion does 
not usually occur in patients with hyperlac­
tatemia alone, but hyperlactatemia from 
“occult” hypoperfusion (not detectable by 
routine monitoring) might be a precursor to 
overt hypoperfusion.
• Lactic acidosis can occur secondary to 
marked tissue hypoxia and hypoperfusion, 
certain drugs or toxins, or congenital defects 
in carbohydrate metabolism.
• Blood lactate measurement is a useful tool 
for assessing severity of tissue hypoxia, 
response to therapy, and prognosis:
◦ In human trauma and shock patients, 
lactate predicts outcome, and mortality 
is correlated with severity of lactic 
acidosis.
◦ Lactate concentrations are increased in 
critically ill and injured dogs; severity of 
hyperlactatemia is associated with 
outcome.
• Serial lactate measurement allows the 
clinician to assess the response of critically ill 
patients to resuscitative therapy (decreasing 
lactate concentration indicates restoration of 
tissue oxygen delivery).SYSTEMS AFFECTED
• Cardiovascular—persistent lactic acidosis 
associated with impaired cardiac contractility, 
impaired pressor response to catecholamines, 
increased sensitivity of myocardium to 
ventricular arrhythmias, and reduced cardiac 
output. These changes may worsen organ 
hypoperfusion, leading to further tissue 
hypoxia.
• As acidosis and tissue hypoxia become 
severe, failure of multiple organ systems and 
death can occur.
SIGNS
Signs relate more to underlying disorder than 
to direct effects of acidosis. As tissue hypoper ­
fusion, hypoxia, and acidosis worsen, signs of 
dysfunction can occur in any organ system.
Disorders causing lactic acidosis are common; 
historical facts should prompt suspicion of an 
underlying acidosis.
• Tachypnea is usually present due to 
attempted respiratory compensation.
• Most patients with acidosis are hypovolemic 
and demonstrate poor tissue perfusion or 
dehydration—dark mucous membranes, 
prolonged capillary refill time, or increased 
skin turgor.
• Severely acidotic patients might have 
cardiac dysrhythmias and weak pulses.
CAUSES
• T wo types of hyperlactatemia, A and B, 
based on presence or absence of hypoper­
fusion or tissue hypoxia.
• Type A hyperlactatemia—more common; 
due to decreased or inadequate oxygen 
delivery or increased oxygen demand. Causes 
of type A hyperlactatemia include shock, 
regional hypoperfusion, arterial obstruction, 
severe hypoxemia or anemia, carbon 
monoxide poisoning, and severe motor 
seizures.
• Increased oxygen demand can be caused by 
increased muscle activity (e.g., exercise, 
tremors, struggling, fever, seizure activity).
• Type B hyperlactatemia—all other causes of 
lactic acidosis; subdivided into three subsets 
(B1, B2, B3); characterized by absence of 
hypoxemia or poor tissue perfusion. Many 
causes of type B lactic acidosis might be 
“occult” hypoperfusion not detectable by 
routine monitoring parameters or possibly 
combinations of types A and B lactic acidosis.
◦ Type B1 hyperlactatemia is associated 
with diseases such as sepsis, neoplasia, liver 
disease and diabetes mellitus.
◦ Type B2 hyperlactatemia is associated 
with a wide variety of drugs or toxins including corticosteroids, activated 
charcoal, propofol, lactulose, morphine, 
terbutaline, theophylline, xylitol, and 
parenteral nutrition.
◦ Type B3 hyperlactatemias are caused by 
congenital metabolic diseases, 
mitochondrial myopathies, and enzyme 
deficiencies.
• Most common causes of type B lactic 
acidosis in veterinary medicine include 
neoplasia, alkalosis, sepsis, renal failure, 
liver disease, catecholamine use 
(norepinephrine, epinephrine), and 
intoxications (strychnine, cyanide, ethylene 
glycol, salicylates, acetaminophen, 
propylene glycol).
• Elevated blood lactate has been observed in 
patients with lymphoma and meningioma. 
Though the type and cause of hyperlac­
tatemia in these animals is not clearly 
understood, the presence of a high lactate 
should prompt the clinician to evaluate other 
markers of perfusion (heart rate, mucous 
membrane color, pulse quality, capillary refill, 
serum creatinine) before attempting 
aggressive fluid resuscitation.
• Metformin intoxication is associated with 
severe lactic acidosis and hypoglycemia in 
people and dogs.
Risk factors for hyperlactatemia are risk 
factors for specific disorders that cause tissue 
hypoxia.
  DIAGNOSIS
Differential diagnoses for hyperlactatemia and 
lactic acidosis include those disorders described 
under Causes.
• Activated charcoal, catecholamines, 
salicylates, acetaminophen, terbutaline, 
nitroprusside, halothane, bicarbonate, and 
propylene glycol can cause mild ­to­moderate 
hyperlactatemia in the absence of true tissue 
hypoperfusion and hypoxia.
• Lower lactate concentrations are found in 
blood samples with sodium citrate anticoagu­
lant than in those with heparin and EDTA.
• Even small amounts of lactate ­containing 
intravenous fluids (e.g., lactated Ringer’s 
solution) can cause false increases in measured 
blood lactate concentration if not properly 
cleared from the catheter prior to sampling.
Results
• Stress, trembling, resisting restraint, 
excitement, and venous stasis can increase

806  Blackwell’s Five-Minute Veterinary Consult  
Llactate to 2.5–5.0 mmol/L, but lactate usually 
normalizes in ≤2 hours.
• Seizures or extreme muscular exertion can 
increase lactate to 4–10 mmol/L, but lactate 
usually normalizes in ≤2 hours.
• Several types of neoplasia increase lactate 
concentrations because tumor cells 
preferentially use anaerobic glucose 
• Alkalosis, sepsis, liver disease, and renal 
failure can also increase lactate concentrations 
by mechanisms other than poor tissue 
perfusion and hypoxia.
• Failure to detect hyperlactatemia does not 
ensure adequate perfusion to all organs; 
significant organ hypoperfusion can still exist 
that might ultimately lead to multiple organ 
failure.
• Regional hypoperfusion, especially 
splanchnic, occurs in the absence of, or 
before, increases in systemic lactate and often 
despite therapy that successfully maintains 
blood pressure, cardiac output, and 
respiratory parameters.
• d­Lactate is not detected by routine 
analysis. Although d­lactate normally only 
exists at 1–5% the concentration of 
l­lactate, d­lactate elevation has been 
associated with short bowel syndrome and 
exocrine pancreatic insufficiency in humans. 
In cats, d­lactate has been associated with 
gastrointestinal disease, diabetic keto­
acidosis, and propylene glycol intoxication.
• d­Lactate hyperlactatemia is a rare cause of 
high anion gap acidosis.
• Yes; semiautomated and automated 
techniques are available for rapid measure­
ment of lactate concentration in microliter 
samples of whole blood, serum, and plasma.
• Lactate should be sampled from comparable 
sites (e.g., all venous or arterial) for serial 
• CBC generally reflects underlying 
cause(s).
• Biochemical and urinalysis findings can 
help determine underlying cause of acidosis; 
examples include renal azotemia and 
increased serum osmolality seen with 
ethylene glycol intoxication; renal azotemia, 
hyperkalemia, and tubular casts seen with 
acute renal failure; and increased total 
protein and increased hematocrit with 
hemoconcentration and poor tissue 
perfusion in a hypovolemic patient.
• Blood gas analysis (arterial preferred to 
assess blood oxygen) might define extent of a 
concurrent respiratory disorder or a mixed 
acid–base disorder.• Additional tests (e.g., ethylene glycol, serum 
and urine glucose and ketones) might be 
helpful, depending on suspected cause.
  TREATMENT
• Hyperlactatemia is more important as a 
marker of severe or developing systemic 
problems. Aggressive treatment is not 
recommended for elevated blood lactate in 
the absence of other signs of circulatory 
shock. Fluid resuscitation is also not indicated 
if cardiogenic shock is the cause.
• Hyperlactatemia, with or without acidosis, 
should drive the clinician to seek causes of 
hypoperfusion and should focus early 
therapeutic interventions to improve tissue 
oxygen delivery.
• If lactic acidosis is severe, aggressive 
therapy to correct underlying cause(s) and 
specifically treat acidosis or hypoperfusion is 
• Specific drug and fluid use depends on 
• Many causes of hyperlactatemia and lactic 
acidosis are characterized by hypovolemia; 
thus, IV fluid therapy is generally first step in 
treatment (unless cardiogenic).
• Alkalinizing and pH ­neutral isotonic 
crystalloid fluids might be preferred (vs. 0.9% 
NaCl) in cases of hypovolemic lactic acidosis 
to more rapidly normalize blood pH.
• Though controversial, sodium bicarbonate 
therapy to correct blood pH <7.1 might be 
indicated when the pH fails to increase in 
response to aggressive fluid resuscitation or 
when cardiovascular collapse is suspected to 
be due to low blood pH.
• Sodium bicarbonate should only be used to 
correct pH to 7.2. This can be accomplished 
by calculating the bicarbonate deficit or 
giving an empirical dose of 1 mEq/kg IV and 
rechecking blood pH.
• Sodium bicarbonate is more likely to be 
effective in patients with a normal anion gap 
metabolic acidosis (normal lactate) than 
patients with high anion gap metabolic 
acidosis, as the latter will correct acidemia 
when organic anions (lactate or ketoacids) are 
converted to bicarbonate during hemo­
dynamic recovery.
• 10–15% of administered bicarbonate is 
converted to CO2; it is important that only 
patients with adequate ventilation are treated.• Complications of sodium bicarbonate 
therapy can include volume overload, 
paradoxic central nervous system acidosis, 
hypocalcemic tetany and a left ­shift of 
oxygen–hemoglobin dissociation curve 
(iatrogenic alkalosis).
  FOLLOW-UP
• Serial lactate determinations are more 
valuable than single measurements; monitor 
lactate over time in critical patients.
• The ability of a patient to clear lactate 
predicts response to therapy and survival.
• Monitor other parameters that gauge 
response to therapy of underlying cause.
Owners should understand early warning 
signs of condition(s) that led to lactic acidosis 
in their pet with instructions to seek prompt 
medical attention should they recur.
• Dogs with hyperlactatemia and acidosis 
have poorer outcomes, similar to humans.
• Lactate >6–6.5 mmol/L suggests tissue 
hypoperfusion (e.g., shock) or local ischemia 
(e.g., gastric necrosis in patients with gastric 
dilatation and volvulus [GDV]).
• Lactic acidosis should correct with 
resuscitation. Lactic acidosis that fails to 
respond is a grave prognostic indicator.
• Hypotensive dogs without hyperlactatemia 
have a better prognosis and chance of survival 
than do hypotensive dogs with hyperlactatemia.
• Hypotensive, normolactatemic cats in an 
intensive care unit have a significantly greater 
chance of survival to hospital discharge than 
their hyperlactatemic counterparts.
• Lactic acidosis can be found with any 
condition causing tissue hypoxia.
• Hyperlactatemia in patients with lymphoma 
and meningioma may exist despite normal 
tissue oxygen delivery. In these patients, other 
parameters should be used to assess tissue 
perfusion as blood lactate can remain elevated 
despite adequate resuscitation.
SEE ALSO
Acidosis, Metabolic.
• GDV = gastric dilatation and volvulus.Lactic Acidosis (Hyperlactatemia)  (continued)

Canine and Feline, Seventh Edition  807
L Suggested Reading
Ateca LB, Dombrowski SC, Silverstein DC. 
Survival analysis of critically ill dogs with 
hypotension with or without 
hyperlactatemia: 67 cases (2006–2011). 
J Am Vet Med Assoc 2015, 
246(1):100–104.
Kohen CJ, Hopper K, Kass PH, et al. Retrospective evaluation of the prognostic 
utility of plasma lactate concentration, base 
deficit, pH, and anion gap in canine and 
feline emergency patients. J Vet Emerg Crit 
Care 2018, 28(1):54–61.
Rosenstein PG, Hughes D. Hyperlactatemia. In: 
Silverstein DC, Hopper K, eds., Small Animal 
Critical Care Medicine, 2nd ed. Philadelphia, 
PA: Elsevier, 2015, pp. 300–305.Shea EK, Dombrowski SC, Silverstein DC. 
Survival analysis of hypotensive cats 
admitted to an intensive care unit with 
or without hyperlactatemia: 39 cases 
(2005–2011). J Am Vet Med Assoc 2017, 
250(8):887–893.
Consulting Editor  Patty A. Lathan(continued)  Lactic Acidosis (Hyperlactatemia)

808  Blackwell’s Five-Minute Veterinary Consult  
LLameness
  BASICS
A disturbance in gait and locomotion in 
response to pain, anatomic disruption, or injury.
• Severe, sharp pain—limited limb move-
ment during all phases of locomotion, little to 
no load bearing in motion or at rest.
• Milder, dull, or aching pain—reduced 
loading and ground contact time during all 
phases of locomotion.
• Pain produced only during certain phases of 
movement—patient adjusts its motion and 
gait to minimize discomfort.
• Anatomic dysfunction resulting in certain 
normal motions being altered or impossible.
• Nervous.
• Any age or breed of dog.
• Age, breed, and sex predilection—depend 
on specific disease.
SIGNS
• Unilateral forelimb—head and neck moves 
upward when the affected limb is placed on 
the ground and drops when the sound limb 
loads.
• Unilateral hind limb—pelvis drops when 
affected leg loads, rises when it unloads.
• Bilateral hind limb—thoracic limbs carried 
lower and shifted caudally at the stance, to 
shift weight forward.
• Always assess the patient’s neurologic status, 
especially with a suspected proximal lesion.
• Complete history—identify known trauma; 
alterations with weather, exercise tolerance, 
response to rest, effect of previous treatments.
• Determine speed of onset of lameness.
• Determine progression—static, slow, rapid.
• Determine consistency—intermittent, 
constant, associations with interventions, rest 
or activities.
• How does the patient show pain?
• Perform a complete routine examination.
• Observe posture—standing, getting up or 
lying down, sitting.
• Observe gait—walking; trotting; climbing 
stairs; tight turns or figure eights.
• Palpate—asymmetry of muscle mass (measure 
and compare); note bony prominences.
• Manipulate bones and joints, beginning 
distally and working proximally.
• Assess—instability; incongruency; pain; 
range of motion (measure); abnormal sounds 
or crepitus.• Examine suspected area of involvement 
last—by starting with normal limbs, patient 
may relax, allowing comparison of normal to 
abnormal reactions.
CAUSES
Forelimb
Growing Dog (<12 Months of Age)
• Osteochondrosis of the shoulder.
• Shoulder luxation or subluxation— 
• Osteochondrosis of the elbow.
• Ununited anconeal process.
• Medial coronoid disease.
• Elbow incongruity.
• Avulsion or calcification of the flexor 
muscles—elbow.
• Asymmetric growth of the radius and ulna.
• Hypertrophic osteodystrophy.
• T rauma—soft tissue; bone; joint.
• Infection—local; systemic.
• Nutritional imbalances.
• Congenital anomalies.
Mature Dog (>12 Months of Age)
• Bicipital tenosynovitis.
• Calcification or mineralization of 
supraspinatus or infraspinatus tendon.
• Contracture of supraspinatus or 
infraspinatus muscle.
• Soft tissue or bone neoplasia—primary; 
• Polyneuritis.
Hind Limb
• Hip laxity (hip dysplasia).
• Avascular necrosis of femoral head—Legg–
Calvé–Perthes disease.
• Osteochondritis of stifle.
• Patella luxation—medial or lateral.
• Osteochondritis of hock.
• Degenerative joint disease (hip dysplasia).
• Cruciate ligament disease.
• Avulsion of long digital extensor tendon.
• Polyneuritis.RISK FACTORS
Breed, size, overweight, strenuous activity, 
metabolic disease (Cushing’s, 
hypothyrodism).
  DIAGNOSIS
Must differentiate musculoskeletal from 
neurogenic and metabolic causes.
Muscle injury elevates creatine phosphokinase 
levels. General inflammatory disease such as 
infectious inflammatory arthropathies have 
been associated with elevations of C-reactive 
protein (CRP).
Depends on suspected cause, however various 
tests available for infectious or inflammatory 
diseases.
IMAGING
• Radiographs—recommend two views of 
region of interest. Stressed views indicated 
if ligamentous injury is part of the 
differential list.
• CT, MRI, ultrasound, and nuclear 
scintigraphy where appropriate.
• Cytologic examination of joint fluid—
identify and differentiate intra-articular 
disease.
• Electromyogram (EMG)—differentiate 
chronic neuromuscular from musculoskeletal 
disease.
• Muscle and/or nerve biopsy—reveal and 
identify neuromuscular disease.
  TREATMENT
(NSAIDs) and Analgesics
• May be used for symptomatic treatment; 
minimize pain, decrease inflammation.
• Carprofen 2.2 mg/kg PO q12h or  
4.4 mg/kg PO q24h.
• Deracoxib 1–2 mg/kg PO q24h, chewable.
• Firocoxib 5 mg/kg PO q24h.
• Grapiprant 2 mg/kg PO q24h, to animals 
>3.6 kg.
• Meloxicam—load 0.2 mg/kg PO, then 
0.1 mg/kg PO q24h—liquid.
• Tepoxalin—load 20 mg/kg, then 10 mg/kg 
PO q24h.

Canine and Feline, Seventh Edition  809
L
hepatic toxicity may preclude use in some 
patients.
• Chondroprotective drugs, such as polysul-
fated glycosaminoglycans, green-lipped 
mussel extract, and glucosamine/chondroitin 
sulfate (limited supportive data), may help 
limit associated cartilage damage and 
• Nonspecific anti-inflammatory supplements—  
e.g. green-lipped muscle extract and omega 3 
fatty acid supplementation.  FOLLOW-UP
SEE ALSO
Chapters covering musculoskeletal and 
neuromuscular disorders.
• CRP = C-reactive protein.
• EMG = electromyogram.
• NSAID = nonsteroidal anti-inflammatory drug. Suggested Reading
Brinker WO, Piermattei DL, Flo GL. 
Physical examination for lameness. In: 
and Fracture Repair, 3rd ed. Philadelphia, 
PA: Saunders, 1997, pp. 228–230.
Renberg WC, Roush JK. Lameness. Vet Clin 
North Am Small Anim Pract 2001, 31:1.
Acknowledgment  The author/editor 
available online(continued)  Lameness

810  Blackwell’s Five-Minute Veterinary Consult  
LLaryngeal and Tracheal Perforation
  BASICS
OVERVIEW
T racheal perforation is a loss of integrity of 
the tracheal wall, allowing leakage of air to 
create subcutaneous (SC) emphysema, 
pneumomediastinum, pneumopericardium, 
pneumothorax, and pneumoretroperitoneum. 
Caused by penetrating, intraluminal, or blunt 
cervical or thoracic trauma. Severity ranges 
from small perforation to complete avulsion. 
With complete avulsion, mediastinal tissues 
can form a pseudomembrane to maintain 
airway patency. Laryngeal perforation is 
disruption of laryngeal structures (thyroid, 
cricoid, and arytenoid cartilages) and can 
create similar leakage of air and may result in 
upper airway obstruction.
• Respiratory—compromise of airway, possible 
pneumomediastinum and pneumothorax. 
Laryngeal swelling may result in upper airway 
• Cardiovascular—pneumothorax and 
tension pneumothorax can decrease venous 
return and cardiac output.
• Nervous, musculoskeletal—depends on 
severity of hypoxia.
• Skin—SC emphysema, initially cervical but 
can affect entire body.
Dog and cat—no breed, age, or sex 
SIGNS
• Onset: immediate or up to 1 week after 
injury.
• SC emphysema and respiratory distress are 
• Other signs—respiratory distress, may have 
stridor, anorexia, lethargy, exercise intolerance, 
gagging, ptyalism, vomiting, coughing, 
hemoptysis, upper airway obstruction, and 
shock. May have dysphonia (voice change) 
and/or dysphagia.
• Access to outside while unsupervised 
causing increased risk of all types of trauma.
• Exposure to other animals causing increased 
risk of bite wounds.
• Penetrating cervical wounds—bite wounds, 
impalement, projectile missiles, foreign 
bodies.
• Iatrogenic perforation during endotracheal 
intubation, transtracheal wash, jugular 
venipuncture, cervical surgery, radiation therapy, 
tracheal stent fracture, or failure to deflate cuff 
or to stabilize the tube while repositioning 
patient. Overinflation of endotracheal cuff can 
cause a linear tear in the trachealis muscle at 
thoracic inlet or intrathoracic trachea. Occurs 
most often with dental procedures.• Blunt trauma can cause intrathoracic 
tracheal avulsion.
• Blunt trauma to the cervical region can 
cause laryngeal avulsion or fracture.
  DIAGNOSIS
• Anesthesia—barotrauma resulting in 
alveolar rupture and pneumothorax.
• Penetrating wounds—perforation of 
esophagus or cervical bite.
• After blunt trauma—pulmonary 
contusions, pneumothorax, rib fractures.
• Differentials for tracheal perforation include 
intrathoracic tracheal compression by 
mediastinal mass, spontaneous pneumothorax, 
pleural effusion, and bronchoesophageal fistula.
• Differentials for laryngeal perforation 
include trauma to caudal pharynx or larynx, 
pharyngeal or laryngeal mass (such as 
squamous cell carcinoma, lymphoma, 
granuloma, other), laryngeal paralysis, abscess, 
pharyngeal mucocele, foreign body in airway.
Arterial blood gas analysis can show hypoxemia, 
hypercarbia, and respiratory acidosis.
IMAGING
• Lateral cervical and thoracic radiographs are 
essential. SC emphysema, pneumomediastinum, 
pneumopericardium, and pneumo  thorax can 
be seen. Also evaluate for concurrent thoracic 
trauma (e.g., rib fractures), and noncardiogenic 
pulmonary edema.
• In cases of tracheal avulsion, site of 
disruption may be visible.
• In cases of laryngeal trauma may observe 
disruption of the hyoid apparatus.
• Abdominal radiographs occasionally show 
pneumoretroperitoneum.
• CT can be useful to identify location and 
extent of laryngeal and tracheal damage. 
Laryngeal and hyoid fractures and 
dislocations can be visualized.
• Laryngoscopy and tracheoscopy used to 
confirm laryngeal or tracheal perforation or 
avulsion and characterize severity; false 
negatives can occur.
• If patient does not have a patent airway, can 
be stabilized with general anesthesia and a 
temporary tracheostomy. Laryngoscopy can 
then be performed.
• Larynx should be evaluated for symmetry 
and function of laryngeal structures, presence of
• hematomas, exposed cartilage, foreign body, 
or flaps of laryngeal mucosa.
• Esophagoscopy performed to rule out 
concurrent esophageal injury.  TREATMENT
• Hospitalization is indicated.
• Oxygen supplementation with 95% O2 for 
4 hours will decrease SC emphysema.
• Minimal handling to reduce stress; most 
cases of iatrogenic perforation will heal.
• If pneumothorax develops, thoracocentesis 
± thoracostomy tubes may be required.
• Intubation if needed.
• If patient decompensates, surgical 
exploration is indicated.
• T racheal rupture secondary to blunt 
trauma or penetrating injury requires 
surgical repair.
• If tracheal avulsion is present, intubate only 
the proximal segment using an undersized 
endotracheal tube. Avoid positive-pressure 
ventilation to prevent disruption of pseudo- 
membrane.
• Cervical tracheal perforation—approach via 
ventral midline; may require a partial median 
sternotomy. Damaged areas of trachea are 
often on the dorsolateral surface: debride and 
repair with 3-0 to 5-0 monofilament 
absorbable suture.
• T racheal resection and anastomosis indicated 
for severe tracheal damage or tracheal avulsion.
• Intrathoracic tracheal avulsion—approach 
via a right lateral 3rd or 4th intercostal 
thoracotomy. Open the pseudomembrane 
and intubate the caudal segment. Preplace 
sutures, guide an endotracheal tube from the 
cranial segment into the caudal segment, and 
complete repair.
• If upper airway obstruction or unable to 
intubate, an emergency temporary tracheo -
stomy is indicated. Temporary tracheostomy 
is performed at approximately the 4th 
tracheal ring and tube is sized to about 50% 
of tracheal lumen.
• Laryngeal repair indicated if avulsed/
exposed arytenoid cartilage with debridement 
or partial arytenoidectomy or tieback 
procedure. If there is collapse or fracture of 
the cricothyroid cartilages, laryngeal 
exploration via ventral laryngotomy may be 
needed to stabilize laryngeal structures to 
reduce stenosis.
• Hyoid bone avulsion and laryngotracheal 
avulsion should be repaired with apposition 
via ventral approach.
• Mucosal flaps should be trimmed and 
edges apposed with 4-0 or 5-0 absorbable 
suture.
• Intraluminal stents can be used for 
preventing adhesions, collapse, and other 
• Stents will require second procedures 3–4 
weeks later for removal.
• Unilateral arytenoid lateralization (tieback) 
if traumatic laryngeal paralysis without 
fractures or if arytenoid avulsion.

Canine and Feline, Seventh Edition  811
L• Permanent tracheostomy may be indicated 
if unable to restore patent airway or with 
severe laryngeal damage.
• Exercise restriction for 3–4 weeks post 
trauma and surgical repair.
• No neck leads and harness only when leash 
walking.
• Broad-spectrum antibiotic therapy if caused 
by bite wounds.
• Antibiotics after obtaining cultures from 
contaminated wounds; continue 1–2 weeks 
in the postoperative period. Empirical 
selections while awaiting culture results 
could include:
◦ Ampicillin 22 mg/kg IV q8h (both dogs 
and cats) and enrofloxacin 10–15 mg/kg 
diluted and given slowly IV or PO q24h in 
dogs (5 mg/kg q24h in cats).
◦ Clindamycin 10 mg/kg IV or PO q8h and 
either amoxicillin/clavulanic acid 15 mg/kg 
PO q12h or enrofloxacin, as listed above.
◦ Corticosteroids (dexamethasone sodium 
phosphate 0.1–0.2 mg/kg IV) at time of 
surgery to reduce inflammation; may repeat 
at a dose of 0.05–0.1 mg/kg IV q24h for 
first 24–48 hours.
• Sedation—use with caution, can decrease 
respiratory drive.
• Corticosteroids are not indicated unless 
there is a large degree of upper airway 
swelling or concern for postoperative 
swelling.
  FOLLOW-UP
• Monitor respiratory rate and effort, mucous 
membrane color, capillary refill time, pulse 
quality, and heart rate, and auscult frequently.• Pulse oximetry and/or arterial blood gases.
• Thoracic radiographs to monitor pneumo-
mediastinum, pneumothorax, and help detect 
tracheal stenosis. T racheoscopy required in 
• T racheostomy care if tracheostomy is 
needed.
• Respiratory rate and effort, respiratory 
noise, and exercise tolerance, during and after 
the recovery stage.
• Use of 3 mL syringe for cuff inflation for 
cats and small dogs to prevent overinflation of 
cuff.
• High-volume low-pressure endotracheal 
tube cuff may also reduce risk of tracheal 
damage.
• Disconnect endotracheal tube from 
anesthetic circuit when repositioning animal 
during anesthesia.
• Selection of appropriate endotracheal tube 
and endoscope size along with use of 
lubrication will reduce iatrogenic tracheal and 
laryngeal trauma.
• Direct visualization of the larynx for 
intubation can reduce risk of iatrogenic 
trauma.
• Long-term intubation for positive-pressure 
ventilation can be maintained by temporary 
tracheostomy to prevent laryngeal damage.
• T racheal stricture and stenosis at site of 
perforation or repair.
• Laryngeal paralysis from damage to 
recurrent laryngeal nerve.
• Dehiscence of tracheal anastomosis site.
• Stenosis or stricture resulting in airway 
compromise.
• Infection from trauma, or post operatively.
• Sepsis (rare).
• Obstruction of temporary or permanent 
tracheostomy with mucus.
• Death, particularly at induction of 
anesthesia with complete tracheal avulsion, or 
with complete airway obstruction.
• Most cases respond well to appropriate 
therapy.• Complete tracheal avulsion—guarded 
prognosis. Without surgery—extremely poor 
prognosis due to stricture formation.
• Prognosis depends on severity of trauma, 
concurrent injuries, and treatment.
• If severe laryngeal trauma is present and 
veterinary care can be quickly obtained, 
permanent tracheostomy can allow for fair to 
good prognosis (with the exception of cats 
and very small dogs, where stoma obstruction 
with mucus may be recurrent and severe).
With tracheal perforation caused by blunt 
trauma, can have pulmonary contusions, 
pneumothorax, rib fractures, and 
hemothorax.
Hypoxia can result in fetal distress and death.
• SC = subcutaneous.
Basdani EE, Papazoglou LG, Patsikas MN, 
et al. Upper airway injury in dogs secondary 
to trauma: 10 dogs (2000–2011). J Am 
Anim Hosp Assoc 2016, 52:291–296.
Jordan CJ, Halfacree ZJ, Tivers MS. Airway 
injury associated with cervical bite wounds 
in dogs and cats: 56 cases. Vet Comp 
Orthop T raumatol 2013, 26:89–93.
Mitchell SL, McCarthy R, Rudloff E, Pernell 
RT. T racheal rupture associated with 
intubation in cats: 20 cases (1996–1998). 
J Am Vet Med Assoc 2000, 216:1592–1595.
Nelson AW. Laryngeal trauma and stenosis. 
2003, pp. 845–857.
White RN, Burton CA. Surgical management 
of intrathoracic tracheal avulsion in cats: 
long-term results in 9 consecutive cases. Vet 
Surg 2000, 29:430–435.
Authors  Lori S. Waddell and David A. Puerto
Consulting Editor  Elizabeth Rozanski(continued)  Laryngeal and Tracheal Perforation

812  Blackwell’s Five-Minute Veterinary Consult  
LLaryngeal Diseases
  BASICS
• The larynx is made of cartilage structures 
surrounding the rima glottis. The functions 
of the larynx are to control airflow during 
respiration, protect the lower airways from 
aspiration during swallowing, and control 
phonation. • Laryngeal diseases in dogs and 
cats include laryngeal paralysis, laryngitis, 
laryngeal collapse, foreign body obstruction, 
neoplasia, and trauma.
• Decreased diameter of the laryngeal opening 
increases resistance to airflow during inspira -
tion and results in stridor on inspiration. The 
decrease in airflow will lead to hypoxemia, 
cyanosis, and/or respiratory distress and a 
decrease in heat exchange (heat intolerance, 
hyperthermia). • Inflammation or lesions of 
the vocal cords can lead to aphonia or change 
in bark/meow.
• Respiratory—respiratory distress, often 
associated with airway obstruction. Aspiration 
pneumonia may develop. Stridor is common. 
• Cardiovascular—hypoxemia/distress may lead 
to tachycardia; laryngeal stimulation may trigger 
vagal response (bradycardia). 
• Gastrointestinal—retching, regurgitation, 
vomiting, and/or dysphagia can occur when 
polyneuropathy causes laryngeal paralysis and 
esophageal dysfunction; esophagitis is frequently 
associated with brachycephalic airway syndrome 
(BAS). • Nervous—depression, stupor, or coma 
may occur if severe laryngeal obstruction leads 
to severe hyperthermia. Older dogs with 
laryngeal paralysis often have geriatric-onset 
laryngeal paralysis polyneuropathy (GOLPP), 
which includes hind limb weakness.
GENETICS
• Juvenile laryngeal paralysis in the bouvier des 
Flandres is transmitted as a dominant trait. • In 
laryngeal paralysis associated with polyneuro -
pathy in the Leonberger dog, X-linked 
inheritance is suggested. • No other laryngeal 
disorder has been proven to be genetic in the 
dog or cat, but familial conditions and breed 
predispositions have been reported.
• More common in dogs than in cats. 
• Currently, congenital laryngeal paralysis is 
only sporadic in the bouvier des Flandres. 
• Idiopathic laryngeal paralysis is a common 
disease of older large-breed dogs; exact 
prevalence unknown. • BAS is a common 
syndrome in French and English bulldogs. 
• Laryngeal trauma may occur in conjunction 
with bite wounds; tracheal bite wounds may 
result in laryngeal paralysis/collapse due to 
damage to the recurrent laryngeal nerves. 
• Neoplasia is rare in dogs, but fairly common in older cats, who are often initially thought 
to have lower airway disease due to “wheezing” 
that accompanies laryngeal masses.
Species
• Familial laryngeal paralysis/polyneuropathy 
complex occurs in the Dalmatian, Rottweiler, 
Leonberger, and Pyrenean mountain dog 
(great Pyrenees). • Congenital laryngeal 
paralysis is found in bouviers des Flandres, 
huskies, husky crosses, white German 
shepherd dogs, and probably bull terriers. 
• Idiopathic acquired laryngeal paralysis is 
most often found in large-breed dogs 
(especially Labrador and golden retrievers). 
• BAS is found in brachycephalic breeds of 
dogs. • Upper airway obstruction due to 
laryngeal collapse or narrowed laryngeal 
opening occurs in Norwich terriers.
• Congenital and familial laryngeal paralysis—
onset of signs usually in the first months of life 
(2 and 8 months). Later in the Leonberger, 
1–9 years, and white German shepherd dog, 2 
years. • Acquired laryngeal paralysis—possible 
at any age but more frequent in older dogs. 
• Neoplasia—middle-aged to old dogs.
SIGNS
• Panting. • Exercise and heat intolerance. 
• Noisy respiration. • Change of voice. 
• Occasional cough. • Severe cases—
inspiratory respiratory distress, collapse, 
syncope, or even sudden death. 
• Polyneuropathy, polymyopathy, or 
myasthenia gravis—regurgitation, weakness, 
abnormal gait (pattern of abnormalities varies). 
• Absence of signs is possible in Norwich 
terriers with upper airway obstruction.
• Panting, polypnea, and inspiratory stridor in 
canine cases. • Respiration is less noisy in cats 
with laryngeal disease. • Cyanosis. 
• Hyperthermia frequent. • Aspiration 
pneumonia—fever, crackles on respiratory 
auscultation. • Polyneuropathy, polymyopathy, 
or myasthenia gravis—paraparesis or tetraparesis 
with decreased spinal reflexes. • Leonberger 
with familial polyneuropathy—high-stepping 
pelvic-limb gait with depressed spinal and 
cranial nerve reflexes. • Rottweilers with 
laryngeal paralysis/polyneuropathy complex—
cataracts frequently observed. • Normal physical 
examination in some Norwich terriers with 
CAUSES
• Laryngeal paralysis: ◦ Congenital—(1) 
neuronal degeneration of the nucleus ambiguous 
(bouvier des Flandres and husky); (2) idiopathic. 
◦ Acquired—(1) polyneuropathy: idiopathic; familial (laryngeal paralysis–polyneuropathy 
complex); immune-mediated; (2) myasthenia 
gravis; (3) polymyopathy: idiopathic; immune-
mediated; infectious (toxoplasmosis, neosporo -
sis); (4) ventral cervical or cranial thoracic 
lesion—neoplasia or trauma affecting one or 
both recurrent nerves; examples include 
lymphoma of the vagus nerve in the cat and 
traumatic neuropathy secondary to thyroid -
ectomy. • Acute laryngitis: ◦ Cause often not 
found. ◦ Virus—canine parainfluenza virus, 
feline herpesvirus 1. ◦ Bacteria— Bordetella 
bronchiseptica . ◦ Gastroesophageal reflux. 
• Idiopathic chronic obstructive laryngitis 
(lymphoplasmacytic, granulomatous). 
• Laryngeal neoplasia: ◦ Dog—rhabdomyoma, 
rhabdomyosarcoma, adenocarcinoma, squamous 
cell carcinoma, lipoma, extramedullary 
plasmacytoma. ◦ Cat—lymphoma, squamous 
cell carcinoma. • T rauma: injuries caused by 
foreign bodies. • Neck trauma, bite wounds. 
• Laryngeal collapse secondary to BAS. 
• Idiopathic laryngeal malformation, collapse in 
Norwich terriers.
Breed associations. Risk factors for developing 
severe or fatal clinical signs include obesity, 
dark coat, hot or humid temperature 
(especially in a closed environment), and 
concurrent lower airway or pulmonary disease.
  DIAGNOSIS
• Pharyngeal diseases—also cause gagging, 
stridor, and cough. Dysphagia is not seen 
with laryngeal disease but may be present in 
the case of pharyngeal lesion. • T racheal 
diseases may be confused with laryngeal 
disease in some cases. Cough is more frequent 
in tracheal disease than in laryngeal disease, 
while inspiratory stridor is more frequent in 
laryngeal disease.
• No specific abnormalities. • Leukocytosis 
may be present in aspiration pneumonia. 
• Mild-to-moderate increase in liver enzymes 
if chronic hypoxemia. • Hypercholesterolemia 
may be present if concurrent hypothyroidism 
If laryngeal paralysis is secondary to polyneu-
ropathy/polymyopathy, these may be 
considered, but are low yield:
• Thyroid panel in the dog. • Antibody titers 
against Toxoplasma gondii  (dog and cat) and 
Neospora caninum  (dog). • Anticholinesterase 
receptor antibody titer.
IMAGING
• Thoracic radiographs—to rule-out 
aspiration pneumonia as a complication, 
other lower airway conditions, and a

Canine and Feline, Seventh Edition  813
Lmediastinal mass as a cause of laryngeal 
paralysis. • If vomiting/regurgitation 
present—barium swallow with fluoroscopy 
(to identify esophageal dysfunction, reflux 
esophagitis/hiatal hernia coexisting in some 
cases of brachycephalic airway syndrome). 
• Pharynx/larynx radiographs or ultrasono -
graphy—to identify potential mass.
Laryngoscopy
• Method of choice to identify laryngeal 
paralysis, collapse, mass, trauma, foreign 
body, or laryngitis. • General anesthesia or 
deep sedation is required. • Laryngeal 
paralysis: ◦ Diagnosis confirmed by loss of 
abduction of arytenoid cartilages during 
deep inspiration. ◦ Usually bilateral but 
unilateral paralysis is possible in the early 
course of the disease. ◦ Unilateral paralysis 
has been described in cats. ◦ False-positive 
result possible because of the influence of 
general anesthesia on laryngeal function. 
Intravenous doxapram HCl (1–2 mg/kg) to 
increase respiratory effort is advised if the 
diagnosis is in doubt.
Esophagoscopy
When vomiting/regurgitation is observed, to 
rule out reflux esophagitis or hiatal hernia.
Retrograde Rhinoscopy
When pharyngeal disease is suspected or in 
the case of BAS.
• Laryngeal paralysis: ◦ Gross findings—
redness, swelling, and thickening of the 
arytenoid cartilages and the vocal folds. 
◦ Histopathology—nonspecific edema and 
inflammation of laryngeal mucosa and 
submucosa; denervation atrophy of laryngeal 
muscles in the case of neuropathy of recurrent 
laryngeal nerve(s). • Idiopathic chronic 
obstructive laryngitis: ◦ Histopathology—
lymphoplasmacytic, granulomatous, or 
pyogranulomatous inflammation of the 
laryngeal submucosa.
  TREATMENT
• Paralysis: ◦ Surgical palliation (arytenoid 
lateralization) is recommended for dogs with 
clinical signs but may be associated with 
postoperative aspiration. ◦ If signs are mild, 
avoidance of triggers is advised (e.g., heat, 
humidity). • Emergency: ◦ Sedation/
anesthesia; supplemental oxygen; cooling 
therapy. ◦ Do not sedate to “look” with the 
thought to do surgery in the future as 
aspiration may occur on recovery. • Cats with 
suspected laryngeal masses may be very 
difficult to intubate; be sure to have surgical supplies for urgent tracheostomy readily 
• Paralysis: ◦ Avoid warm, poorly ventilated 
environments, stress, and intense excitation as 
these further compromise normal cooling 
mechanisms and proper air exchange. 
◦ Avoid cervical collars. ◦ Avoid weight gain.
ACTIVITY
Exercise should be severely restricted in 
animals suffering from laryngeal paralysis, 
especially in warm temperatures.
DIET
Loss of weight is advocated in overweight 
patients with any upper airway disorder.
• Paralysis: ◦ Discuss the importance of 
surgery and the risk of not performing 
surgery (chronic hypoxemia, heat stroke, risk 
of suffocation, and death) in moderately to 
severely affected dogs. ◦ Discuss potential 
complications of surgery including aspiration 
pneumonia. ◦ Discuss the potential 
progression of neuromuscular disease. 
◦ Discuss the potential heritability of this 
condition in certain breeds. • Neoplasia: 
◦ Discuss surgical/chemotherapeutical 
options.
• Paralysis: ◦ Surgery (unilateral arytenoid 
lateralization) is the treatment of choice in 
both dogs and cats; bilateral surgical correc -
tion is not advised because it increases the risk 
of aspiration pneumonia. ◦ Cats that are 
breathing comfortably but have a voice change 
alone may be managed medically. • Neoplasia: 
◦ Surgery, radiation or chemotherapy. 
◦ Permanent tracheostomy in dogs may 
improve quality of life if surgical excision is 
not possible.
• Paralysis—if surgery is declined, anxiolytic 
may be considered. • Lymphoma (mainly in 
cats)—chemotherapy (see Lymphoma—
Cats).
Usual safety precautions if chemotherapy is 
administered.
  FOLLOW-UP
• Immediate postsurgical period—check 
rectal temperature (should remain normal). 
• Monitor for aspiration pneumonia (short and long term). • If surgery is successful, 
exercise, stridor, and heat intolerance should 
decrease.
• Paralysis—recurrence of clinical signs are 
uncommon if surgery is correctly performed; 
aspiration pneumonia is possible as the larynx 
is placed in a fixed open position; risk of 
aspiration pneumonia increased if bilateral 
arytenoid lateralization is performed or if 
dysphagia due to pharyngeal and/or esophageal 
dysfunction coexists. • T umor—recurrence of 
clinical signs if complete resection is not 
possible; increased risk of aspiration 
pneumonia in the postoperative period.
• Idiopathic paralysis—good with surgery; 
guarded to poor if surgery is declined.
• Paralysis associated with esophageal 
dysfunction—poor. • T umor—guarded to 
good in the case of successful resection of a 
benign tumor; poor in the case of carcinoma, 
even with radiation therapy; variable in the 
case of feline lymphoma.
• Laryngeal paralysis is sometimes associated 
with a mass in the anterior mediastinum or 
the ventral cervical region. • Coexistence of 
megaesophagus, weakness, or abnormal gait 
with laryngeal paralysis suggests 
polyneuropathy, polymyopathy, or 
Congenital and familial laryngeal paralysis—
onset of clinical signs in the first year of life.
Dogs affected with congenital laryngeal 
paralysis or laryngeal paralysis/polyneuropa-
thy complex should not be bred.
SEE ALSO
• BAS = brachycephalic airway syndrome.
• GOLPP = geriatric-onset laryngeal paralysis 
Dominique Peeters and Cécile Clercx. 
available online(continued)  Laryngeal Diseases

814  Blackwell’s Five-Minute Veterinary Consult  
LLead Toxicosis
  BASICS
Intoxication (blood lead >0.35 ppm, although 
somewhat variable) owing to acute or chronic 
exposure to some form of lead.
• Cell damage is due to the ability of lead to 
substitute for other polyvalent cations 
(especially divalent cations such as Ca and Zn) 
important for cell homeostasis. • Diverse 
biological processes are affected, including 
metal transport, energy metabolism, apoptosis, 
ion conduction, cell adhesion, inter- and 
intracellular signaling, enzymatic processes, 
protein maturation, and genetic regulation.
• Gastrointestinal—unknown mechanism; 
likely damage to peripheral nerves. 
• Nervous—capillary damage; alteration of 
membrane ionic channels and signaling 
molecules. • Renal/urologic—damage to 
proximal tubule cells due to enzyme 
disruption and oxidative damage. • Hemic/
lymph/immune—interference with hemo-
globin synthesis; increased fragility and 
decreased survival of red blood cells (RBCs); 
release of reticulocytes and nucleated RBCs 
from bone marrow; inhibition of 5 ′-pyrimi-
dine nucleotidase causing retention of RNA 
degradation products; aggregation of 
ribosomes resulting in basophilic stippling.
• T rue incidence unknown. • Decreasing 
prevalence in dogs—owing to elimination of 
sources. • Steady to increasing prevalence in 
cats—increased awareness and diagnosis. 
• Higher prevalence during warmer months. 
• Higher prevalence in young animals—
greater bioavailability of lead and more 
permeable blood–brain barrier.
• Low socioeconomic status of pet-owning 
family associated with high blood lead 
concentration in pets. • Areas with older 
homes/buildings.
Species
Dogs and cats—dogs more commonly than cats.
N/A
Mainly dogs <1 year of age.
N/A
SIGNS
• Primarily gastrointestinal and neurologic. 
• Gastrointestinal—often precede CNS signs; predominant with chronic, low-level 
exposure. • CNS—occur more often with 
acute exposure, more common in younger 
animals. • Renal—proximal tubular 
nephropathy has been reported.
Historical iFindings
History of renovation of older house or 
building or ingestion of lead objects.
• Vomiting. • Diarrhea. • Anorexia. 
• Abdominal pain. • Regurgitation due to 
megaesophagus. • Lethargy. • Hysteria. 
• Seizures. • Blindness. • Cats—central 
vestibular abnormalities such as vertical 
nystagmus and ataxia reported.
CAUSES
• Ingestion of some form of lead—paint and 
paint residues or dust from sanding; car 
batteries; linoleum; solder; plumbing 
materials and supplies; lubricating 
compounds; putty; tar paper; lead foil; golf 
balls; lead object (e.g., shot, fishing sinkers, 
drapery weights); leaded glass. • Use of 
improperly glazed ceramic food or water 
bowl. • Lead paint or lead-contaminated dust 
or soil are common sources for exposure; cats 
ingest lead as a result of self-grooming.
• Age <1 year. • Living in economically 
depressed areas. • Living in old house or 
building that is being renovated. • Feeding 
trimmings from lead-shot game.
  DIAGNOSIS
Dogs
• Canine distemper. • Infectious encephalitides. 
• Epilepsy. • Bromethalin, methylxanthine, or 
tremorgenic mycotoxin toxicosis. 
• Nonsteroidal anti-inflammatory drug 
(NSAID) toxicosis. • Heat stroke. • Intestinal 
parasitism. • Intussusception. • Foreign body. 
• Pancreatitis. • Infectious canine hepatitis.
Cats
• Degenerative or storage diseases. • Hepatic 
encephalopathy. • Infectious encephalitides. 
• Organophosphate, bromethalin, or 
methylxanthine toxicosis.
• Between 5 and 40 nucleated RBCs/100 
white blood cells (WBCs) without anemia. 
• Absence of nucleated RBCs does not rule 
out the diagnosis. • Anisocytosis, 
polychromasia, poikilocytosis, target cells, 
hypochromasia. • Basophilic stippling of 
RBCs; often difficult to detect. 
• Neutrophilic leukocytosis. • Cats—
elevated aspartate aminotransferase (AST) 
and alkaline phosphatase (ALP) reported. • Urinalysis—mild nonspecific renal 
damage; glucosuria; proteinuria; 
Lead Concentration
• Toxic—antemortem whole blood: 
>0.35 ppm (35  μg/dL); postmortem liver 
and/or kidney: >5 ppm (wet weight). 
• Blood lead concentrations fluctuate and 
do not necessarily correlate with total body 
burden. • Lower values—must be inter -
preted in conjunction with history and 
clinical signs. • No normal “background” 
blood lead concentrations; typically less 
than 0.05 ppm. • Blood concentrations—
do not correlate with occurrence or severity 
of clinical signs. • CaNa2EDTA mobiliza -
tion test—collect one 24-hour urine 
sample; administer CaNa2EDTA (75 mg/kg 
IM); collect a second 24-hour urine sample; 
with toxicosis, urine lead increases 10- to 
60-fold post-EDTA (succimer could 
conceivably be substituted for CaNa2EDTA 
but this has not been evaluated). • Point-
of-care testing is available, but results might 
underestimate true blood lead concentra -
tions; confirmation of results using other 
techniques such as GFAAS or ICP-MS is 
IMAGING
May note radiopaque material in gastro -
intestinal tract; not diagnostic.
N/A
• Gross—may note paint chips or lead 
objects in gastrointestinal tract. 
• Intranuclear inclusion bodies—may be 
noted in hepatocytes or renal tubular 
epithelial cells; intracellular storage form of 
lead; considered pathognomonic. 
• Cerebrocortical lesions—spongiosis, 
vascular hypertrophy, gliosis, neuronal 
necrosis, demyelination.
  TREATMENT
• Inpatient—first course of chelation, 
depending on severity of clinical signs. 
• Outpatient—orally administered 
chelators.
• Balanced electrolyte fluids—Ringer’s 
solution; replacement of hydration deficit. 
• Gastric lavage or whole bowel irrigation—
ACTIVITY
N/A

Canine and Feline, Seventh Edition  815
LDIET
N/A
• Inform client of the potential of adverse 
human health effects of lead. • Notify public 
health officials. • Determine the source of the 
lead.
Removal of lead objects from the gastro -
• Evacuation of gastrointestinal tract—
saline cathartics; sodium or magnesium 
sulfate (dogs 2–25 g; cats 2–5 g PO as 20% 
solution or less). • Control of seizures—
diazepam (given to effect; dogs and cats 
0.5 mg/kg IV) or phenobarbital sodium 
(administer in increments of 10–20 mg/kg 
IV to effect). • Alleviation of cerebral 
edema—mannitol (0.25–2 g/kg of 15–25% 
IV, slow infusion over 30–60 minutes) and 
dexamethasone (2.2–4.4 mg/kg IV). 
• Some evidence that antioxidants or 
thiol-containing drugs may be useful—  
vitamins C and E, α-lipoic acid, 
N-acetylcysteine; optimal doses not 
determined. • B vitamins, especially 
thiamine, may also be useful; optimal doses 
not determined. • Reduction of lead body 
burden—chelation therapy: ◦ CaNa2EDTA 
(dogs and cats, 25 mg/kg SC, IM, IV q6h 
for 2–5 days); dilute to a 1% solution with 
D5W before administration; may need 
multiple treatment courses if blood lead 
concentration is high; allow 5-day rest 
period between treatment courses. 
◦ Succimer—alternative to CaNa2EDTA; 
orally administered chelating agent; 10 mg/
kg PO q8h for 5 days followed by 10 mg 
PO q12h for 2 weeks; allow 2-week rest 
period between treatments; may administer 
per rectum if clinical signs such as emesis 
preclude oral administration; cats success -
fully treated with 10 mg/kg PO q8h for 
17 days. Advantages over other chelators: 
can be given PO, allowing for outpatient 
treatment; does not increase lead absorp -
tion from the gastrointestinal tract; not 
reported to be nephrotoxic; chelation of 
essential elements such as zinc and copper 
is not clinically significant.CONTRAINDICATIONS
CaNa2EDTA—do not administer to patients 
with renal impairment or anuria; establish 
urine flow before administration; do not 
administer orally.
• CaNa2EDTA—safety in pregnancy not 
established; teratogenic at therapeutic doses 
although in human medicine is recommended 
over succimer for pregnant patients. 
• Succimer—safety in pregnancy not 
established; fetotoxic at doses much higher 
(100–1000 mg/kg) than recommended 
therapeutic dose.
CaNa2EDTA—depletion of zinc, iron, and 
manganese with long-term therapy.
N/A
  FOLLOW-UP
Blood lead—should be <0.1 ppm; assess 
10–14 days after cessation of chelation 
therapy.
• Test paint, dust, soil prior to animal access 
if likelihood of lead contamination. 
• Determine source of lead and remove it 
from the patient’s environment.
Occasionally, permanent neurologic signs 
(e.g., blindness).
• Signs should dramatically improve within 
24–48 hours after initiating chelation therapy. 
• Prognosis—favorable with treatment. 
• Uncontrolled seizures—guarded prognosis.
N/A
Dogs <1 year of age—more likely to be 
affected.
None; however, humans in the same 
environment may be at risk for exposure.PREGNANCY/FERTILITY/BREEDING
• T ransplacental passage—may cause 
neonatal poisoning.
• Lactation—lead mobilized from bones 
unlikely to poison nursing animals.
SYNONYMS
Plumbism
SEE ALSO
• ALP = alkaline phosphatase.
• AST = aspartate aminotransferase.
• GFAAS = graphite furnace atomic 
absorption spectrometry
• ICP-MS = inductively coupled plasma mass 
• NSAID = nonsteroidal anti-inflammatory 
drug.
• RBC = red blood cell.
• WBC = white blood cell
Braton R, Kowalczyk D. Lead poisoning. In: 
Kirk, R., ed. Current Veterinary Therapy X. 
Philadelphia, PA: Saunders, 1989, pp. 
152–159.
Knight TE, Kent M, Junk JE. Succimer for 
treatment of lead toxicosis in two cats. J Am 
Vet Med Assoc 2001, 218:1946–1948.
Knight TE, Kumar MSA. Lead toxicosis in 
cats—a review. J Feline Med Surg 2003, 
5(5):249–255.
Morgan RV. Lead poisoning in small 
companion animals: an update (1987–
1992). Vet Hum Toxicol 1994, 36:18–22.
Morgan RV, Moore FM, Pearce LK, et al. 
Clinical and laboratory findings in small 
companion animals with lead poisoning: 
347 cases (1977–1986). J Am Vet Med 
Assoc 1991, 199:93–97.
Morgan RV, Pearce LK, Moore FM, et al. 
Demographic data and treatment of small 
Assoc 1991, 199:98–102.
Ramsey DT, Casteel SW, Fagella AM, et al. 
Use of orally administered succimer 
(meso-2,3-dimercaptosuccinic acid) for 
treatment of lead poisoning in dogs. J Am 
Vet Med Assoc 1996, 208:371–375.
VanAlstine WG, Wickliffe LW, Everson RJ, 
et al. Acute lead toxicosis in a household of 
cats. J Vet Diagn Invest 1993, 5:496–498.
Author  Robert H. Poppenga
Consulting Editor  Lynn R. Hovda(continued)  Lead Toxicosis

816  Blackwell’s Five-Minute Veterinary Consult  
LLeft Anterior Fascicular Block
  BASICS
• Conduction delay or block in the anterior 
fascicle of the left bundle branch (Figures 1 
and 2). • Left ventricle activation is altered 
or delayed toward the blocked fascicle and 
corresponding papillary muscle. 
• Controversial terminology in veterinary 
cardiology because, in contrast to humans, 
dogs and cats do not appear to have an 
anatomic left anterior fascicle.
Electrocardiogram (ECG) Features
• QRS complex—normal duration. • Left axis 
deviation—dogs, <+40°; cats, <0°: ◦ Small q 
waves and tall R waves in leads I and aVL—
small q not essential. • Deep S waves (exceeding 
the R waves) in leads II, III, and aVF .
• Anatomic basis still speculative—anterior 
fascicle vulnerable because it has a single 
blood supply, is long and thin, and is 
located in the turbulent outflow tract of the 
left ventricle. • No hemodynamic 
GENETICS
N/A
• Most commonly described form of bundle 
branch block in cats. • Uncommon in dogs.
N/A
Species
N/A
N/A
N/A
SIGNS
• Signs usually associated with the underlying 
cause. • Usually an incidental ECG finding.
No associated signs or hemodynamic 
CAUSES
• Hypertrophic cardiomyopathy (cats). 
• Left ventricular hypertrophy (e.g., mitral 
insufficiency, aortic stenosis, aortic body 
tumor, hypertension, hyperthyroidism). 
• Hyperkalemia (e.g., urethral obstruction, 
acute renal insufficiency, Addison’s disease). • Ischemic cardiomyopathy (e.g., arterio -
sclerosis of the coronary arteries, myocardial 
infarction, myocardial hypertrophy that 
obstructs coronary arteries). • Surgical 
repair of a cardiac defect (e.g., ventricular 
septal defect or aortic valvular disease). 
• Restrictive cardiomyopathy (cats). 
• Fibrosis. • Often noted in otherwise 
normal individuals.
N/A
  DIAGNOSIS
• Left ventricular enlargement—absence of 
left ventricular enlargement on thoracic 
radiograph or cardiac ultrasound supports a 
diagnosis of left anterior fascicular block. 
• Right bundle branch block—deep, wide S 
waves in leads I, II, III, and aVF causing a 
right axis deviation; in patients with left 
anterior fascicular block, leads I and aVL are 
positive and leads II, III, and aVF have deep 
S waves resulting in a left axis deviation. 
• Altered position of the heart within the 
thorax—thoracic radiographs help identify 
mass or foreign body that may be displacing 
the heart. • Suspect hyperkalemia if signs of 
urethral obstruction, renal insufficiency, or 
hypoadrenocorticism (Addison’s disease); 
determine serum potassium concentration.
Hyperkalemia possible.
N/A
IMAGING
• Echocardiogram may show structural heart 
disease. • Thoracic and abdominal radiographs 
may show mass, pulmonary metastatic lesion, 
foreign body, or abnormal cardiac position.
• Electrocardiography. • Long-term 
ambulatory monitoring (Holter) may reveal 
intermittent bundle branch block.
Possible lesions or scarring on endocardial 
surface in the path of the bundle branches; 
applying Lugol’s iodine to the endocardial 
surface within 2 hours post mortem enables 
clear visualization of the conduction 
system.
  TREATMENT
• T reatment unnecessary. • T reat underlying 
disease if present.NURSING CARE
Unnecessary
ACTIVITY
Unrestricted unless indicated by underlying 
DIET
No modifications unless indicated by 
Fascicular block per se does not cause 
hemodynamic compromise; combined with 
right bundle branch block it may develop 
into second- or third-degree AV block, 
making treatment essential; need to treat 
underlying cause if present.
N/A
T reatment directed toward possible 
underlying primary disease (e.g., drugs to 
lower the serum potassium in hyperkalemia).
N/A
N/A
N/A
  FOLLOW-UP
ECG regularly.
N/A
Causative lesion could progress and lead to a 
more serious arrhythmia or complete heart 
block.
No hemodynamic compromise.
N/A
N/A
N/A
N/A

Canine and Feline, Seventh Edition  817
L
SEE ALSO
Degree).
• Left Bundle Branch Block.
• Right Bundle Branch Block.ABBREVIATIONS
• AV = atrioventricular. 
• ECG = electrocardiogram.
Diagnosis of Arrhythmias, 2nd ed. Milan, 
Italy: Edra S.P .A., 2018.
Tilley LP . Essentials of Canine and Feline 
Electrocardiography, Interpretation and 
T reatment, 3rd ed. Baltimore, MD: Williams and Wilkins, 1992.
In: Smith FWK, Tilley LP , Oyama M, Sleeper 
M, eds., Manual of Canine and Feline 
Cardiology, 5th ed. St. Louis, MO: Saunders 
Elsevier, 2016, pp. 49–76.
Willis R, Oliveira P ., Mavropoulou A. Guide 
II I III aVR aVL aVF
Figure 2.
Left anterior fascicular block in a cat with hypertrophic cardiomyopathy. Severe left axis deviation (−60°) with a qR pattern in leads I and aVL and an rS pattern 
in leads II, III, and aVF . The QRS complexes are of normal duration. (Source: From Tilley LP . Essentials of Canine and Feline Electrocardiography, 3rd ed. 
Baltimore: Williams & Wilkins, 1992. Reprinted with permission of Wolters Kluwer.)
Figure 1 .
Left anterior fascicular block in a dog with hyperkalemia (serum potassium, 5.3 mEq/L). There is abnormal left axis deviation (−60°) with a qR pattern in leads I 
and aVL and an rS pattern in leads II, III, and aVF . The large T waves are compatible with hyperkalemia. (Source: From Tilley LP . Essentials of Canine and 
Feline Electrocardiography, 3rd ed. Baltimore: Williams & Wilkins, 1992. Reprinted with permission of Wolters Kluwer.)(continued)  Left Anterior Fascicular Block

818  Blackwell’s Five-Minute Veterinary Consult  
LLeft Bundle Branch Block
  BASICS
Conduction delay or block in both the left 
posterior and left anterior fascicles of the left 
bundle (Figures 1 and 2); a supraventricular 
impulse activates the right ventricle first 
through the right bundle branch; the left 
ventricle is activated late, causing the QRS to 
become wide and bizarre.
• QRS prolonged—dogs >0.08 seconds; cats 
>0.06 seconds. • QRS wide and positive in 
leads I, II, III, and aVF . • Block can be 
intermittent or constant.
• Because the left bundle branch is thick 
and extensive, the lesion causing the block is 
often large. • Usually an incidental ECG 
finding—does not cause hemodynamic 
GENETICS
N/A
Uncommon in cats and dogs. In cats with 
hypertrophic cardiomyopathy, left bundle 
branch block is not as commonly seen as left 
anterior fascicular block.
N/A
Species
N/A
N/A
N/A
SIGNS
• Usually an incidental ECG finding—does 
not cause hemodynamic abnormalities. 
• Signs may be associated with the underlying 
condition if present.
Does not cause signs or hemodynamic 
CAUSES
• Cardiomyopathy. • Direct or indirect cardiac 
trauma (e.g., hit by car, cardiac needle 
puncture). • Neoplasia. • Subvalvular aortic 
stenosis. • Fibrosis. • Ischemic cardiomyopathy 
(e.g., arteriosclerosis of the coronary arteries, myocardial infarction, myocardial hypertrophy 
that obstructs coronary arteries).
N/A
  DIAGNOSIS
• Left ventricular enlargement.
• No left ventricular enlargement on 
thoracic radiograph or cardiac ultrasound 
studies supports diagnosis of isolated left 
bundle branch block. • Can also be 
confused with ventricular ectopic beats, but 
the PR interval is usually constant and left 
bundle branch block does not result in pulse 
deficits.
N/A
N/A
IMAGING
• Echocardiography may reveal structural 
heart disease; absence of left heart enlarge -
ment supports a diagnosis of left bundle 
branch block. • Thoracic and abdominal 
radiographs may show masses or pulmonary 
metastatic lesions; traumatic injuries could 
result in localized or diffuse pulmonary 
densities.
• ECG. • Long-term ambulatory monitoring 
(Holter) may reveal intermittent left bundle 
system.
  TREATMENT
Directed toward the underlying cause if 
Generally not necessary.
ACTIVITY
Unrestricted unless required for management 
of underlying condition.
DIET
management of underlying condition.CLIENT EDUCATION
• Left bundle branch block per se does not 
cause hemodynamic abnormalities. 
• Lesion causing the block could progress, 
leading to more serious arrhythmias or 
complete heart block.
N/A
N/A (unless required for management of 
underlying condition).
N/A
N/A
N/A
N/A
  FOLLOW-UP
Serial ECG may show clearing or progression 
to complete heart block.
N/A
• Causative lesion could progress, leading to a 
block. • First- or second-degree atrioventricular 
(AV) block may indicate involvement of the 
right bundle branch.
PROGNOSIS
N/A
N/A
N/A
N/A
SEE ALSO
Degree).

Canine and Feline, Seventh Edition  819
L
• Left Anterior Fascicular Block.
• Right Bundle Branch Block.
• AV = atrioventricular.
• ECG = electrocardiogram. Suggested Reading
T reatment, 3rd ed. Baltimore, MD: 
Williams and Wilkins, 1992.
Tilley LP , Smith FWK, Jr. Electrocardiography. In: Smith FWK, 
Tilley LP , Oyama M, Sleeper M, eds., 
5th ed. St. Louis, MO: Saunders Elsevier, 
2016, pp. 49–76.
Figure 2.
Left bundle branch block in a cat with hypertrophic cardiomyopathy. The QRS complex is of 0.07-second duration and is positive in leads I, II, III, and aVF . 
Neither a Q wave nor an S wave occurs in these leads. The QRS complex is inverted in leads aVR. (Source: From Tilley LP . Essentials of Canine and Feline 
Electrocardiography, 3rd ed. Baltimore: Williams & Wilkins, 1992. Reprinted with permission of Wolters Kluwer.)
II I III aVR aVL aVF CV5RL CV6LU
Figure 1 .
Intermittent left bundle branch block in a Chihuahua. QRS complexes are wider (0.07–0.08 seconds) in the second, third, and fourth complexes and in the last 
three complexes. Consistent PR interval confirms a sinus origin for the abnormal-appearing QRS complexes (lead II, 50 mm/s, 1 cm = 1 mV). (Source: From Tilley 
LP . Essentials of Canine and Feline Electrocardiography, 3rd ed. Baltimore: Williams & Wilkins, 1992. Reprinted with permission of Wolters Kluwer.)(continued)  Left Bundle Branch Block

820  Blackwell’s Five-Minute Veterinary Consult  
LLegg–Calvé–Perthes Disease
  BASICS
Spontaneous deterioration of the femoral 
head and neck, leading to an incongruent, 
malformed coxofemoral joint and secondary 
osteoarthritis.
• Precise cause unknown; a specific vascular 
lesion not identified.
• Histologic evidence points to infarction of 
vessels supplying the proximal femur.
• Necrosis of subchondral bone leads to 
collapse of subchondral bone and 
deformation of the femoral head during 
normal loading.
• Articular cartilage becomes thickened, 
develops clefts, and undergoes superficial fraying.
• Simultaneous osseous degeneration and 
repair is characteristic of ischemia and 
revascularization of bone.
• No known association with 
hypercoagulability or other coagulopathy.
Musculoskeletal—causes a pelvic limb 
lameness; insidious in onset.
GENETICS
• Manchester terriers have multifactorial 
inheritance pattern with a high degree of 
heritability.
• Probable autosomal recessive inheritance in 
miniature poodles, West Highland white 
terriers, Yorkshire terriers, and pugs.
• Hereditary predisposition likely.
• Most common among adolescent dogs of 
miniature, toy, and small breeds.
• No accurate estimates available.
N/A
Species
Dog
• Toy breeds and terriers are most susceptible.
• Manchester terriers, miniature pinschers, toy 
poodles, Lakeland terriers, West Highland 
white terriers, Yorkshire terriers, Cairn terriers, 
and pugs—higher than expected incidence.
• Most patients are 5–8 months of age.
• Range 3–13 months.
None
SIGNS
Usually unilateral; only 12–16% of cases are 
bilateral.Historical Findings
Progressive pelvic limb lameness that is usually 
insidious in onset over 2–3 months; ranges from 
weight-bearing to non-weight-bearing lameness.
• Pain 
on manipulation of the hip—common.
• Atrophy of the thigh muscles—common.
• Decreased 
range of motion of hip—inconsistent.
• Crepitation of hip—inconsistent.
• Patient otherwise normal.
CAUSES
• Unknown.
• Tamponade of the epiphyseal intracapsular 
subsynovial vessels supplying the femoral 
head is suggested cause of ischemia leading to 
the pathologic changes.
• Other proposed causes include abnormal 
anatomic conformation, increased 
intracapsular pressure, hormonal influences, 
and hereditary factors.
• Adolescent small, toy, and miniature breed 
dogs.
• T rauma to the hip region.
  DIAGNOSIS
• Intracapsular hip trauma (e.g. femoral head 
or neck fracture).
• Severe hip dysplasia (but atypical breeds).
• Femoral head osteochondrosis.
• Infection and neoplasia considered less 
likely in patients with classic signalment, 
clinical findings, and radiographic lesions.
• Medial patellar luxation—differential for 
pelvic limb lameness in young toy breed dogs.
• Rupture of the cranial cruciate ligament—
differential for pelvic limb lameness in older dogs.
N/A
N/A
IMAGING
• Early radiographic changes—widening of 
the joint space; focal decreased or increased 
bone density of the epiphysis; sclerosis and 
thickening of the femoral neck.
• Later radiographic changes—lucent areas 
within the femoral head (apple-core or 
moth-eaten).
• End-stage radiographic changes—flattening 
and extreme deformation of the femoral head; 
severe osteoarthrosis; potential femoral neck 
fractures.
• Advanced imaging (computed tomography 
or magnetic resonance imaging) may be more 
sensitive than radiographs in early stages.DIAGNOSTIC PROCEDURES
N/A
• Femoral head—removed during femoral 
head and neck excision (FHNE) or total hip 
replacement; usually deformed with a 
thickened, irregular articular surface.
• Early disease—histologically characterized 
by loss of lacunar osteocytes and necrosis of 
marrow elements; trabeculae surrounded by 
granulation tissue.
• Later disease—thickened metaphyseal 
trabeculae; mixture of necrosis and repair 
tissue typical of revascularization of bone.
• Advanced disease—osteoclastic activity; 
new bone formation.
  TREATMENT
• Rest and analgesics—successful in 
alleviating lameness in less than 25% of 
patients.
• Ehmer sling—successful in one patient; 
maintained for 10 weeks; increased risk of 
ankylosis. Not widely recommended.
• Insidious onset often prevents early 
recognition and possibility of successful 
conservative treatment.
• FHNE with early and vigorous physical 
therapy after surgery—treatment of choice.
• Micro total hip replacement (THR) has 
been reported to successfully restore normal 
ground reaction forces.
Post Surgery
• Physical therapy—crucial for rehabilitating 
the affected limb.
• Analgesics, anti-inflammatory drugs, and 
cold packing—reduces pain and 
inflammation to increase limb use.
• Range-of-motion exercises initiated 
immediately—reduces risk of muscle 
contraction and limited range of motion.
• Small lead weights attached as ankle 
bracelets above the hock joint—encourages 
early use of the treated limb.
ACTIVITY
• Post surgery—early, low-impact activity 
encouraged to improve leg use.
• Conservative therapy—restricted activity 
DIET
Avoid obesity.
• Warn owners of potential genetic basis of 
the disease in Manchester terriers, miniature 
poodles, Yorkshire terriers, West Highland 
white terriers, and pugs; discourage breeding 

Canine and Feline, Seventh Edition  821
L• Warn client that recovery after FHNE may 
take 3–6 months and requires early and 
vigorous physical therapy.
FHNE or micro THR—treatment of choice.
(NSAIDs)—preoperative or postoperative; 
minimize joint pain; reduce synovitis; reduce 
soft tissue pain and inflammation to 
encourage postsurgery limb use:
• Carprofen 2.2 mg/kg PO q12h or 4.4 mg/kg 
PO q24h.
• Deracoxib 1–2 mg/kg PO q24h, chewable.
• Etodolac 10–15 mg/kg PO q24h.
• Firocoxib 5 mg/kg PO q24h.
• Grapiprant 2 mg/kg PO q24h, to animals 
>3.6 kg.
• Meloxicam—load 0.2 mg/kg PO, then 
• Tepoxalin—load 20 mg/kg, then 10 mg/kg 
PO q24h.
NSAIDs—gastrointestinal disease, liver 
disease, or renal disease may preclude use in 
NSAIDs—can cause gastrointestinal tract 
ulceration, hepatotoxicity, or nephrotoxicity; 
inhibition of platelet activity may increase 
hemorrhage at surgery; discontinue aspirin 
for at least 1 week before surgery, if possible.
NSAIDs—do not use in conjunction with 
glucocorticoids; risk of gastrointestinal tract 
ulceration; consider appropriate wash-out 
times when switching from one NSAID to 
another.
chondroitin sulfate)—minimal benefit in 
advanced disease; no evidence to suggest that 
these drugs prevent or reverse the disease process.
  FOLLOW-UP
• Postsurgical progress checks—1- to 2-week 
intervals depending on progress with limb 
use; ensure compliance with exercise 
recommendations.• Conservative therapy—reevaluate after 4–6 
weeks of strict rest (physical examination, 
radiographs) to determine if surgery is 
needed.
Noncompliance with postsurgical physical 
therapy exercises may result in less than 
optimal limb function.
• FHNE—good to excellent prognosis for 
full recovery (84–100% success rate).
• Micro THR—excellent prognosis for full 
recovery.
• Conservative therapy—reported to alleviate 
lameness after 2–3 months in less than 25% 
of patients.
N/A
Usually affects juvenile small-breed dogs, but 
mature dogs may be affected by chronic disease.
N/A
N/A
SYNONYMS
• Aseptic necrosis of the femoral head.
• Avascular necrosis of the femoral head.
• Coxa magna.
• Coxa plana.
• Osteochondritis juvenilis.
• Perthes disease.
SEE ALSO
• Cruciate Ligament Disease, Cranial.
• FHNE = femoral head and neck excision.
drug.
• THR = total hip replacement.
Bowlus R, Armbrust L, Biller D. Magnetic 
resonance imaging of the femoral head of 
normal dogs and dogs with avascular 
necrosis. Vet Radiol Ultrasound 2008, 
49:7–12.Brenig B, Leeb T, Jansen S, Kopp T. Analysis 
of blood clotting factor activities in canine 
Legg-Calvé-Perthes disease. J Vet Intern 
Med 1999, 13:570–573.
Gambardella PC. Legg-Calvé-Perthes disease 
in dogs. In: Bojrab MJ, ed., Disease 
Mechanisms in Small Animal Surgery, 
2nd ed. Philadelphia, PA: Saunders, 1993, 
pp. 804–807.
Gibson KL, Lewis DD, Perchman RD. Use 
of external coaptation for the treatment of 
avascular necrosis of the femoral head in a 
dog. J Am Vet Med Assoc 1990, 
197:868–869.
Jankovits D, Liska W, Kalis R. T reatment of 
avascular necrosis of the femoral head in 
small dogs with micro total hip 
replacement. Vet Surg 2012, 
41(1):143–147.
2002, 38:467–477.
Peycke L. Femoral head and neck ostectomy. 
NAVC Clinician’s Brief 2011, 9(2):55–59.
Piek CJ, Hazewinkel HAW, Wolvekamp 
WTC, et al. Long term follow-up of 
avascular necrosis of the femoral head in the 
dog. J Small Anim Pract 1996, 37:12–18.
Piermattei DL, Flo GL, DeCamp CE. Hip 
joint. In: Handbook of Small Animal 
Orthopedics and Fracture Repair, 
4th ed. Philadelphia, PA: Saunders, 2006, 
pp. 507–508.
Towle-Millard HA, Breur GJ. Miscellaneous 
orthopedic conditions. In: Veterinary 
Surgery Small Animal, 2nd ed., Vol. 1. 
St. Louis, MO: Elsevier Saunders, 2018, 
pp. 1309.
T rostel CT, Pool RR, McLaughlin RM. 
Canine lameness caused by developmental 
orthopedic diseases: panosteitis, Legg-Calvé-
Perthes disease, and hypertophic 
osteodystrophy. Compend Contin Educ 
Pract Vet 2003, 25(4):282–292.
Author  Laura A. Barbur
acknowledge the prior contribution of Larry 
Carpenter.
available online(continued)  Legg–Calvé–Perthes Disease

822  Blackwell’s Five-Minute Veterinary Consult  
LLeiomyoma, Stomach, Small and Large Intestine
  BASICS
OVERVIEW
Uncommon benign tumor arising from the 
smooth muscle of the stomach and intestinal 
tract; with immunohistochemistry these 
tumors may be reclassified as a gastrointestinal 
stromal tumor (GIST) or GIST-like.
• Middle-aged to older (>6 years) dogs and 
cats.
SIGNS
• Relate to location in the gastrointestinal 
tract.
• Stomach—vomiting.
• Small intestine—vomiting; weight loss; 
borborygmus; flatulence.
• Large intestine and rectum—tenesmus; 
hematochezia; sometimes rectal prolapse.
• Stomach—no specific abnormalities; may 
have melena on rectal exam.
• Small intestine—often no abnormal 
findings; may feel mid-abdominal mass; 
occasionally distended, painful loops of small 
bowel; possible melena on rectal exam.
• Large intestine and rectum—may feel 
palpable mass per rectum; may have bright 
red blood on rectal exam.
Unknown
  DIAGNOSIS
• Adenocarcinoma.
• GIST.
• GIST-like.
• Hypoglycemia—occasionally associated 
with paraneoplastic syndrome.
microcytic hypochromic anemia (iron-
deficiency anemia).
• Abdominal ultrasonography—may reveal a 
thickened wall of stomach or bowel; gastric 
leiomyoma most common at esophageal–
gastric junction.
• Contrast radiography (stomach and small 
intestine)—may reveal a space-occupying mass.
• Double-contrast radiography (large 
intestine and rectum)—reveals a space-
occupying mass.
• Contrast-enhanced CT—highest details of 
gastrointestinal tract and abdominal lymph 
node visualization.
Fine-Needle Aspirates
If mass or thickening seen with ultrasound, 
fine-needle aspirate (FNA) with cytology may 
be performed to rule out other differentials; 
for leiomyomas cytology is generally low yield.
Upper Gastrointestinal Tract
Perform upper gastrointestinal tract endoscopy 
and mucosal biopsy; however, this is frequently 
nondiagnostic because tumors are deep to the 
mucosal surface or distal to scope length. 
Therefore surgical biopsy often required to 
confirm the diagnosis.
Large Intestine and Rectum
Colonoscopy may reveal a mass; mucosal biopsy 
may be nondiagnostic because of normal 
mucosal covering of the tumor; surgical biopsy 
often required. If mass can be palpated per 
rectum, transrectal biopsies may be obtained.
  TREATMENT
curative if tumor is resectable.
• Even large leiomyomas often can be removed 
successfully and cured with narrow margins.
If reclassified as a GIST (c-KIT-positive), may 
consider a tyrosine kinase inhibitor (toceranib 
phosphate) as follow-up therapy.
N/A
 FOLLOW-UP
• Complete resection—normal postoperative 
care; no additional follow-up necessary.
• Monitor blood glucose postoperatively if 
hypoglycemic prior to surgery.  MISCELLANEOUS
Hypoglycemia—recognized as an associated 
paraneoplastic syndrome.
• FNA = fine-needle aspirate.
• GIST = gastrointestinal stromal tumor.
Frost D, Lasota J, Miettinen M. 
Gastrointestinal stromal tumors and 
leiomyomas in the dog: a histopathologic, 
immunohistochemical, and molecular 
genetic study of 50 cases. Vet Pathol 2003, 
40:42–54.
Gillespie V, Baer K, Farrelly J, et al. Canine 
gastrointestinal stromal tumors: 
immunohistochemical expression of CD34 
and examination of prognostic indicators 
including proliferation markers Ki67 and 
AgNOR. Vet Pathol 2011, 48:283–291.
Maas CP , ter Haar G, Van Der Gaag I, et al. 
Reclassification of small intestinal and cecal 
smooth muscle tumors in 72 dogs: clinical, 
histologic, and immunohistochemical 
evaluation. Vet Surg 2007, 36:302–313.
McPherron MA, Withrow SJ, Seim HB, 
Powers BE. Colorectal leiomyoma in seven 
dogs. J Am Anim Hosp Assoc 1992, 
28:43–46.
Tanaka T, Akiyoshi H, Mie K, et al. Contrast-
enhanced computed tomography may be 
helpful for characterizing and staging canine 
gastric tumors. Vet Radiol Ultrasound 
2019, 60(1):7–18.

Canine and Feline, Seventh Edition  823
LLeiomyosarcoma, Stomach, Small and Large Intestine
  BASICS
OVERVIEW
• Uncommon malignant tumor arising from 
smooth muscle of stomach or intestines.
• Locally invasive; metastatic rate up to 50%, 
usually intra-abdominal sites, especially 
lymph nodes and liver.
• Prognosis fair to guarded.
• In large intestine the cecum is often 
affected.
• Analyses reclassified many leiomyosarcomas 
to gastrointestinal stromal tumors (GISTs) or 
GIST-like tumors; differentiate with 
immunohistochemistry.
• T rue leiomyosarcomas (LMS) rare; this 
chapter discusses GISTs with LMS.
• Mostly middle-aged to older ( >6 years).
SIGNS
• Relate to GI tract.
• Stomach—vomiting; weight loss.
diarrhea; borborygmus; flatulence.
• Large intestine and rectum—tenesmus, 
may lead to rectal prolapse; hematochezia.
• Stomach—nonspecific.
mass; sometimes distended, painful loops of 
small bowel.
• Large intestine and rectum—may feel mass 
per rectum.
Unknown
  DIAGNOSIS
• GIST.
• Anemia—may be hypochromic, microcytic 
(iron-deficiency anemia).
• Leukocytosis.
• Hypoglycemia— paraneoplastic syndrome.IMAGING
• Abdominal ultrasonography—may reveal 
mass or mural thickening:
◦ GISTs more likely to have abdominal 
effusion.
◦ Contrast-enhanced CT—highest detail 
for GI tract and abdominal lymph node 
visualization.
Fine-Needle Aspirates (FNA)
• FNA and cytology of mass or GI thickening 
may show malignant mesenchymal cells 
supportive of sarcoma.
• FNA and cytology of intra-abdominal 
lymph nodes important for metastasis 
• Endoscopy and mucosal biopsy—often 
nondiagnostic as tumors are deep to the 
mucosal surface; mass may be beyond reach 
of endoscope.
• Surgical biopsy—often required to confirm 
• Colonoscopy—may allow a mass to be 
seen; mucosal biopsy may be nondiagnostic 
due to normal mucosa covering the tumor.
• Deep biopsy—perform if possible.
Immunohistochemistry on Biopsy
• Perform to differentiate LMS from GIST.
• c-KIT-positive; DOG1 is sensitive and 
specific marker.
  TREATMENT
• Surgical resection—treatment of choice.
• Evaluate for metastasis prior to surgery 
(e.g., mesenteric lymph nodes, liver, lungs).
• If reclassified as a GIST (c-KIT-positive), 
phosphate) as follow-up therapy:
◦ 5/7 dogs with gross disease had clinical 
benefit (3 complete response, 1 partial 
response, 1 stable disease); median 
progression-free survival = 110 weeks.
  FOLLOW-UP
• LMS often metastasize to liver and regional 
lymph nodes.• Older case series:
◦ Small intestine: median survival time 
(MST) 12 months.
◦ Cecum: MST 7.5 months, but most died 
of other diseases.
◦ Gastric: rare, high rate of metastasis, 
short survival.
• Even dogs with metastasis can have 
prolonged survivals; MST 21.7 months in 
one study of dogs with metastatic LMS.
• One report showed similar survival times 
between dogs with leiomyoma, LMS, GIST, 
and GIST-like tumors:
◦ 42 dogs, small intestinal tumors treated 
surgically: 1- and 2-year survivals of 62.6% 
and 52.3%.
◦ 19 dogs, cecal tumors treated surgically: 
1- and 2-year survivals of 84.2% and 66%.
• Mitotic index <9 and histological grade 
were prognostic for survival in abdominal 
visceral soft tissue sarcomas (mostly spleen 
and small intestine).
Hypoglycemia—reported as paraneoplastic 
syndrome.
• LMS = leiomyosarcomas.
• MST = median survival time.
Berger EP , Johannes CM, Jergens AE, et al. 
Retrospective evaluation of toceranib 
phosphate (Palladia®) use in the treatment 
of gastrointestinal stromal tumors of dogs. 
J Vet Intern Med 2018, 32(6):2045–2053.
Hobbs J, Sutherland-Smith J, Penninck D, 
et al. Ultrasonographic features of canine 
gastrointestinal stromal tumors compared to 
other gastrointestinal spindle cell tumors. 
Vet Radiol Ultrasound 2015, 
56(4):432–438.

824  Blackwell’s Five-Minute Veterinary Consult  
LLeishmaniosis
  BASICS
OVERVIEW
• Primary species infecting dogs and cats is 
protozoan Leishmania infantum  which is 
endemic in Mediterranean basin countries, 
the Middle East, Central Asia, China, and 
South and Central America. •  Dogs in the 
United States may acquire infection in 
another country, or part of endemic 
foxhound population (vertical transmission). 
• Sand fly vectors transmit flagellated 
parasites (promastigotes) to skin of host. 
Other modes of transmission include vertical, 
venereal, and blood transfusion. •  Dogs and 
cats—clinical manifestations range from 
subclinical to severe; main systems affected: 
lymphoid organs, skin, eyes, kidneys, liver; 
renal failure is most common cause of death.
• Dogs—purebred dogs (except Ibizan hounds) 
more susceptible; no sex or age predilection. 
• Cats—no breed, sex, or age predilection.
SIGNS
• Similar in dogs and cats. •  Lymphadenomegaly. 
• Nonpruritic, exfoliative, erosive–ulcerative, 
nodular, papular, or pustular dermal and 
mucocutaneous lesions. •  Blepharitis, 
conjunctivitis, keratoconjunctivitis, uveitis. 
• Polyuria, polydipsia. •  Hyporexia, weight 
loss, vomiting, diarrhea, melena. 
• Splenomegaly, hepatomegaly. •  Lameness. 
• Epistaxis. •  Fever (rare).
• T ravel to or acquisition from endemic regions. 
• Coinfections (e.g., E. canis , retroviruses), 
immunosuppression, or malnutrition predispose.
  DIAGNOSIS
• Scaling and alopecia—infectious (bacterial, 
parasitic, fungal) or immune-mediated disease 
(lupus). •  Renal disease—infection 
(pyelonephritis, Lyme nephritis), other 
glomerulonephropathy.
• Hyperproteinemia, hypergamma -
globulinemia (polyclonal). •  Hypoalbuminemia. 
• Nonregenerative normo  cytic normochromic 
anemia. •  Proteinuria—quantitate with urine 
protein/creatinine ratio. •  Leukocytosis or 
leukopenia with lympho  penia. •  Increased 
hepatocellular enzyme activities. •  Renal 
azotemia. •  Thrombocytopenia.
• Protein electrophoresis—differentiate 
polyclonal from monoclonal gammopathy. • Serologic diagnosis (IFA or ELISA)—most 
cross-react to Trypanosoma cruzi ; differentiate 
based on clinical signs, history, and likelihood 
of exposure. In-house immunochromatographic 
tests available. •  PCR—sensitive with aspirates 
of bone marrow, lymph nodes, spleen, skin; 
blood is less sensitive.
Fine-needle aspirates or biopsy of relevant 
tissues.
• Granulomatous, suppurative, or pyogranulo -
matous inflammation, lymphoplasmacellular 
inflammation in skin and hemolymphoid 
tissues. Reactive hyperplasia in lymphoid 
organs. •  Visualization of amastigotes confirms 
diagnosis. Absence of amastigotes does not rule 
out. •  Mucosal ulcerations—nasal, oral, 
  TREATMENT
• Medical management of infection. •  Follow 
IRIS Guidelines for treatment of renal disease 
(see Internet Resources). •  Diet—high-quality 
protein; renal diet as indicated.
• Dogs—meglumine antimoniate (100 mg/kg 
SC q24h or 50–75 mg/kg SC q12h for 1 
month) or miltefosine (2 mg/kg PO q24h for 
1 month). Best in combination with long-term 
allopurinol (10 mg/kg PO q12h for 12–24 
months). Allopurinol may also be used alone. 
• Cats—allopurinol (10 mg/kg PO q12–24h) 
as monotherapy. Short-term meglumine 
antimoniate (20–50 mg/kg SC q24h) plus 
allopurinol is optional.
  FOLLOW-UP
• Monitor clinical signs, laboratory 
abnormalities, and antibody levels 
(quantitative serology) at day 30, 90, 180 and 
then every 6 months. •  Relapses (rise in 
antibody or globulin concentrations and/or 
reappearance of clinical signs, laboratory 
abnormalities) may occur months to years 
after therapy or during therapy if drug 
resistance develops; recheck at least every 2 
months after treatment completion. Drug 
resistance reported for allopurinol. •  Monitor 
for urolithiasis and renal mineralization in 
dogs on long-term allopurinol.PREVENTION/AVOIDANCE
• Topical pyrethroid-based repellents. 
• Canine vaccines available in Europe, parts 
of South America; reduces incidence of 
clinical disease but not subclinical infection.
• Good (lymphadenomegaly, skin lesions) to 
poor (severe renal insufficiency) outcome, 
defined by clinical stage (LeishVet system 
outlines four stages). •  Death usually from 
end-stage glomerulonephritis, nephrotic 
syndrome, and/or hypertension. •  Infection 
may not be completely eliminated; in long- 
term treatment, monitoring required to 
prevent relapses.
• Advise client of risk via exposure to sand 
flies in endemic areas. •  Leishmaniosis is 
reportable in the United States and some 
other countries.
• IFA = immunofluorescence antibody assay.
• LeishVet Staging: http://www.leishvet.org/
fact-sheet/clinical-staging/•  IRIS Guidelines: 
http://www.iris-kidney.com/guidelines/
Pennisi MG, Cardoso L, Baneth G, et al. 
LeishVet update and recommendations on 
feline leishmaniosis. Parasit Vectors 2015, 
8:302.
Solano-Gallego L, Miró G, Koutinas A, et al. 
LeishVet guidelines for the practical 
management of canine leishmaniosis. 
Parasit. Vectors 2011, 4:86.
Authors  Laia Solano-Gallego and Gad 
Baneth

Canine and Feline, Seventh Edition  825
LLeishmaniosis, Cutaneous
  BASICS
Leishmaniosis is a group of infectious diseases 
occurring throughout the Mediterranean 
region, the Middle East, parts of Asia, and 
Central and South America. It is caused by 
parasitic protozoa of the genus Leishmania , 
and Leishmania infantum  is the most common 
cause of disease in the dog. It occurs 
infrequently in the cat.
Infection is transmitted by the bite of 
female sand flies of the genus Phlebotomus  
in Europe and Lutzomia  in the New World. 
Nonvectorial transmission modalities have 
been demonstrated (venereal, vertical, 
dog-to-dog, blood transfusion), but are 
much less common. Following inoculation 
of a small number of promastigotes into the 
dermis, the innate immune response 
(complement, neutrophils, macrophages) 
and then the adaptive response (T-cell-
mediated) attempt to control the infection. 
A high percentage of dogs develop an 
effective T helper-1 response, resulting in 
subclinical infection and becoming 
seronegative or developing a low anti- Leish -
mania  antibody titer. A smaller group of 
dogs develop a predominantly T helper-2 
response, have elevated antibody titers 
(immunoglobulin G [IgGs]), and allow the 
progression of the infection causing lesions 
and clinical signs. Active infection causes 
lesions by different mechanisms, including 
an acute inflammatory response (fever, 
lethargy, asthenia) and granulomatous 
inflammatory lesions, by generating 
immunocomplexes that are deposited in 
different organs causing inflammation and 
tissue damage (glomerulonephritis, 
arthritis, uveitis).
Infection with Leishmania infantum  (CanL) is 
considered systemic. Rarely (papulonodular 
cutaneous form), the infection is exclusively 
cutaneous. From the dermis, infection first 
spreads to the hematopoietic organs (bone 
marrow, lymph nodes, spleen) and then 
systemically. The spread of infection and the 
involvement of numerous organs and systems 
explains the clinical pleomorphism of the 
disease.
GENETICS
Several haplotypes, possibly associated with 
tendency to develop a T helper-2 response, 
are associated with increased susceptibility to 
the development of the disease. Some breeds, 
including German shepherd dog, boxer, 
Rottweiler, Alaskan Malamutes, appear to be 
susceptible. Conversely, some autochthonous 
Mediterranean breeds (e.g., Ibizian hound) respond with an effective cellular response 
and very rarely develop clinical signs.
In areas where CanL is endemic, the preva -
lence of infection is very high (over 50%) with 
seroprevalences ranging between 5% and 30%. 
However, less than 5% of dogs develop clinical 
signs. Isolated cases have been observed in 
non-endemic areas (Northern Europe, United 
States), most often in dogs that have visited 
areas where the disease is endemic.
GEOIGRAPHIC DISTRIBUTION
Found in Mediterranean countries, Portugal, 
the Middle East, Central and South Asia, and 
Central and South America. Vertical 
transmission of CanL has been seen in 
hunting foxhounds in the United States.
No breed or age predisposition.
SIGNS
• Loss of body weight.
• Decreased or increased appetite.
• Generalized lymphadenomegaly.
• Skin lesions:
◦ Nonpruritic dermatitis.
◦ Generalized exfoliative dermatitis with or 
without alopecia.
◦ Erosive–ulcerative dermatitis (planum 
nasale, distal legs, paw pads).
◦ Nodular dermatitis.
◦ Pustular dermatitis.
◦ Papular dermatitis (ventral pinnae, nose, 
abdomen).
• Onychogryphosis.
• Muscle atrophy.
• Mucous membranes pallor.
• Fever.
• Arthritis/articular pain/lameness.
• Ocular lesions: keratoconjunctivitis, 
blepharitis, and uveitis.
CAUSES
Leishmania infantum  (syn. L. chagasi ) 
zymodeme MON1 is a protozoan parasite 
with two structural variants: the amastigote 
form found in mononuclear phagocytes 
within the mammalian host and the infective 
flagellated promastigote form found in the 
sand fly.
Living in an endemic area and outdoors 
lifestyle. Immunosuppression can trigger 
disease progression in a previously 
infected dog.  DIAGNOSIS
Any cause of cutaneous granulomatous 
disease with or without systemic symptoms. 
Leishmaniosis is considered one of the great 
imitators.
• Mild to moderate nonregenerative 
anemia.
• Leukocytosis or leukopenia—lymphopenia, 
neutrophilia, neutropenia.
• Thrombocytopathy.
• Impaired secondary hemostasis and 
• Hyperglobulinemia (polyclonal beta- and/
or gammaglobulinemia).
• Decreased albumin/globulin ratio.
• Renal azotemia.
Cytology—finding Leishmania  amastigotes 
in lymph node or bone marrow smears is 
considered diagnostic with low sensitivity. 
Serum anti- Leishmania  antibodies by 
immunofluorescence antibody test (IFAT) 
or ELISA. Main diagnostic test—dogs with 
clinical CanL usually have high antibody 
titers (>1:80 in IFAT). Biopsies (skin, lymph 
node) are recommended with low or 
borderline titers for histopathology and 
detection of Leishmania  in the tissue with 
immunohistochemistry or PCR. Positive 
PCR for Leishmania  DNA in sample of 
bone marrow, lymph node, or ocular 
conjunctiva is not definitive proof that 
clinical signs are the consequence of 
Leishmania  infection.
IMAGING
Abdominal ultrasonography—splenomegaly.
N/A
Granulomatous inflammation in tissues 
(nodular to diffuse dermatitis, granulomatous 
colitis, granulomatous nephritis).
  TREATMENT
Outpatient medical management except in 
cases with severe organ involvement.
ACTIVITY
N/A

826  Blackwell’s Five-Minute Veterinary Consult  
LDIET
During treatment with allopurinol, a 
low-purine diet is recommended to avoid 
xanthinuria and urolithiasis.
T reatment does not completely eliminate 
infection despite the clinical improvement. 
Dogs remain infected life-long. Regular 
examinations for early detection of disease 
relapses needed. Application of topical 
insecticides (pyrethroids) are necessary to 
minimize the risk of transmission to other 
animals.
N/A
Meglumine antimoniate 100 mg/kg SC q24h 
for 4–6 weeks with allopurinol 10 mg/kg PO 
q12h for at least 6 months. Miltefosine 2 mg/
kg PO q24h (with allopurinol) instead of 
meglumine antimoniate: This combination 
appears to be less effective. The use of 
immunostimulants (domperidone, nucleo-
tides) may reduce the risk of disease relapses. 
T reatment with allopurinol and an immu-
nostimulant (domperidone or nucleotides) 
alone effective in cases of mild or moderate 
disease, but it is generally not effective (not 
recommended) in severe cases.
Meglumine antimoniate is contraindicated in 
patients with severe kidney disease due to 
potential nephrotoxicity.
Meglumine antimoniate causes pain and 
inflammation at injection site; vomiting and 
diarrhea are common side effects. Allopurinol 
can cause development of xanthine uroliths. 
Dogs on long treatment with allopurinol 
should be fed a low-purine diet.
Allopurinol may decrease the hepatic 
metabolism of azathioprine. If used concur-
rently the dosage of azathioprine should be 
reduced by one-third. Allopurinol may 
increase serum cyclosporine level.
Follow-up visits: 4–6 weeks after diagnosis, 
every 3 months during the first year, and then 
every 6 months. A complete physical exam -
ination, CBC, serum biochemistry including 
serum protein electrophoresis, urine analysis, 
and serology should be performed at each 
check-up.
Topical pyrethroids in collars (deltamethrine, 
flumethrin) or spot on (permethrin) have 
been demonstrated to reduce the risk of 
infection and to reduce the prevalence of the 
disease. All dogs living in endemic areas 
should be treated regularly with topical 
pyrethroids. Three protein vaccines are 
currently licensed for CanL: two in Europe 
and one in Brazil. These vaccines are safe and 
have protection efficacies close to 70%. They 
do not prevent infection, but reduce the risk 
of having clinical leishmaniosis if infected. 
They can be administered to dogs living in 
endemic areas along with topical insecticides/
repellents to increase protection. Dogs 
visiting endemic areas should be treated with 
topical pyrethroids.
N/A
Four clinical stages have been defined based 
on clinical signs, serology, pathologic 
abnormalities, and renal disease. Prognosis 
depends on clinical stage: from good in mild 
disease (stage I) to poor in very severe disease 
(stage IV). T reatment causes clinical 
improvement in most dogs. However, dogs 
remain infected life-long.
(e.g., ehrlichiosis) are frequently diagnosed in 
dogs with leishmaniosis. It is recommended 
to test dogs with leishmaniosis for prevalent 
local vector-borne infectious diseases.
N/A.ZOONOTIC POTENTIAL
Leishmaniosis is a zoonosis and dogs are 
considered the most important peri-domestic 
reservoir of L. infantum  infection for humans. 
The ownership of an infected dog does not 
appear to greatly increase the risk of 
developing leishmaniosis. Dogs diagnosed 
with leishmaniosis must be treated and 
monitored, and topical pyrethroids used, to 
prevent transmission of infection. Reporting 
of infection to public health authorities is 
required in some countries.
Leishmaniosis can be transmitted vertically 
and by venereal route. Infected dogs should 
not be used as breeders. Allopurinol is 
considered to be safe during pregnancy. 
Information regarding the risk of using 
meglumine antimoniate in pregnant or 
lactating animals is limited. Use should be 
avoided. Miltefosine is contraindicated in 
pregnant and lactating animals. Puppies born 
to a mother with leishmaniosis should be 
screened for Leishmania  infection with 
serology or PCR of a bone marrow sample at 
3–6 months of age.
SYNONYMS
Leishmaniasis.
• CanL = canine leishmaniosis caused by 
Leishmania infantum .
• IFAT = immunofluorescence antibody test.
http://www.leishvet.org
Noli C, Saridomichelakis M. An update on 
the diagnosis and treatment of canine 
leishmaniosis caused by Leishmania 
infantum  (syn. L. chagasi ). Vet J 2014, 
202:425–435.
Pennisi MG, Persichetti MF . Feline leish-
maniosis. Is the cat a small dog? Vet 
Parasitol 2018, 251:131–137.
Reguera RM, Morán M, Pérez-Pertejo Y, et al. 
Current status on prevention and treatment 
of canine leishmaniasis. Vet Parasitol 2016, 
227:98–114.
Solano-Gallego L, Miró G, Koutinas A, et al. 
Parasites Vectors 2011, 4:86.
Resnick
 Leishmaniosis, Cutaneous  (continued)

Canine and Feline, Seventh Edition  827
L
Lens Luxation
   BASICS
OVERVIEW
• Lens luxation—total dislocation of lens 
from its normal location; occurs when lens 
capsule separates 360° from the zonules that 
hold lens in place.
• Anterior—forward displacement through 
the pupil into anterior chamber.
• Posterior—backward displacement into 
vitreous.
• Subluxation—partial separation of lens 
from its zonular attachments; lens remains 
in a normal or near-normal position in 
pupil.
• Primary (hereditary) luxation—inherited 
zonular defect of dogs resulting in bilateral 
but often asymmetrical clinical signs.
• Congenital luxation—often associated with 
other congenital ocular anomalies.
• Secondary luxation—due to chronic 
inflammation, buphthalmia, intraocular 
neoplasia, senile zonular degeneration, or 
trauma.
• Primary—usually adult dogs (typically 3–6 
years); common breeds include terriers, 
Chinese crested and Chinese Shar-Pei. Rare 
in cats.
• Secondary—dog and cat; any age/breed.
SIGNS
• Fibrils of liquefied vitreous in anterior 
chamber.
• Abnormally shallow (anterior luxation) or 
deep anterior chamber (posterior luxation).
• Abnormal iris curvature secondary to tilting 
of lens.
• Phacodonesis (tremor of lens with globe 
movement).
• Iridodonesis (tremor of iris with globe 
• Aphakic crescent (crescent-shaped area of 
pupil lacking lens).
• Acute or chronic painful eye, episcleral 
injection, diffuse or central corneal edema.
• Glaucoma more common in anterior lens 
luxation but can be detected in any stage.
• Uveitis.
• Primary—associated with ADAMTS17  
gene mutation in some canine breeds; 
inheritance pattern uncertain in others.
• Primary luxation and primary glaucoma—
may occur simultaneously in some breeds.
• Intraocular neoplasia—secondary to 
physical luxation or chronic inflammation.
• T rauma—rarely causes a normal lens to 
luxate without severe ocular injury.• Cataracts—can cause tension and breakage 
of lens zonules.
  DIAGNOSIS
• Uveitis, glaucoma—painful, red eyes with 
corneal edema; may be concurrent.
• Buphthalmia may cause lens luxation.
• Corneal endothelial dystrophy or degenera-
tion may also cause corneal edema.
• Diagnosis made by careful ophthalmic 
examination and history.
Normal, unless systemic disease present.
IMAGING
• Thoracic radiographs, abdominal ultra-
sonography—may be indicated if intraocular 
• Ocular ultrasonography—useful if corneal 
edema or cloudy ocular media preclude 
• Complete ophthalmic examination, 
including tonometry.
• Genetic test available for some predisposed 
breeds.
  TREATMENT
• Potentially visual eyes—immediate referral 
to a veterinary ophthalmologist for possible 
intracapsular lens extraction is indicated.
• Manual trans-corneal reduction of anterior 
lens luxation and medical management of 
posterior luxation has been described.
• Topical miotic therapy may be used to keep 
a posteriorly luxated lens behind pupil and 
avoid surgery in some cases.
• Irreversibly blind eyes can be enucleated or 
eviscerated with intrascleral prosthesis; if 
secondary to neoplasia, enucleation is the best 
choice (therapeutic and diagnostic).
• Topical miotics—demecarium bromide or 
prostaglandin analogs (latanoprost) q12h 
indicated if the lens is primarily subluxated or 
posteriorly luxated.
• If the pupil is blocked due to anterior lens 
luxation, tropicamide may allow the pupil to 
dilate, releasing lens and decreasing risk for 
pupillary block glaucoma.
• Mannitol: 1 g/kg IV over 20 minutes 
indicated for intraocular pressure (IOP) 
>40 mmHg.• Carbonic anhydrase inhibitors—topical 
dorzolamide q8h for high IOP .
• Topical anti-inflammatory—0.1% 
dexamethasone sodium phosphate or 1% 
prednisolone acetate (q6–24h) if inflamma-
tion present.
• Topical miotics—contraindicated if lens in 
anterior chamber.
• Client must verify location of lens prior to 
applying a miotic
• Mannitol—contraindicated in patients with 
cardiac disease, dehydration, pulmonary 
edema, anuria and intracranial bleeding.
  FOLLOW-UP
• Medically treated primary posterior 
luxation—recheck IOP 24 hours after 
starting treatment and frequently thereafter; 
once IOP is stable, re-examine patient 3 or 4 
times/year.
• Monitor for secondary glaucoma and 
• If only one lens is involved at the time of 
examination, the other lens may eventually 
luxate as well; the ophthalmologist may 
choose to perform prophylactic phacoemulsi-
fication in the contralateral eye if not yet 
luxated.
• IOP = intraocular pressure.
Davidson MG, Nelms SR. Diseases of the 
lens and cataract formation. In: Veterinary 
Ophthalmology, 5th ed. Ames, IA: Wiley 
Blackwell, 2013, pp. 1199–1233.
Maggs DJ, Miller PE, Ofri R. Diseases of the 
lens. In: Slatter’s Fundamentals of Veterinary 
Ophthalmology, 6th ed. St. Louis, MO: 
Saunders, 2018, pp. 306–333.
acknowledge the prior contribution of Filipe 
Espinheira.

828  Blackwell’s Five-Minute Veterinary Consult  
LLeptospirosis
  BASICS
• Caused by pathogenic members of genus 
Leptospira ; each serovar has own virulence 
factors, infectious dose, route of exposure. 
• Acute and chronic diseases of dogs (mainly 
nephritis and hepatitis) and rarely cats. 
• Dogs—serovars causing disease vary by 
geographic area; recent serovars of concern 
in the United States are L. grippotyphosa , 
L. autumnalis , and L. pomona ; vaccines 
should include regional serovars.
• Leptospira  penetrate intact/cut skin/mucous 
membranes; rapidly invade bloodstream (4–7 
days); disseminated spread (2–4 days). 
• Invasion leads to transient fever, leuko­
cytosis, mild hemolysis and hemoglobinuria, 
albuminuria. • Capillaries—endothelial cell 
damage. • Liver—hepatic necrosis. 
• Kidney—leptospiruria; Leptospira  localize 
in damaged renal tubules; organism replicates 
in tubular epithelium. • Serum antibodies 
appear as bacteremia decreases. • Death—
usually due to interstitial nephritis, vascular 
damage, renal failure; may result from 
septicemia, disseminated intravascular 
coagulopathy (DIC), respiratory failure.
• Cardiovascular—endothelial cell damage, 
hemorrhage. • Hepatobiliary—hepatitis, 
necrosis. • Nervous—meningitis. • Renal/
urologic—focal interstitial nephritis, hemo­
globinuric nephrosis, tubular damage/failure. 
• Respiratory—vasculitis, interstitial pneumo ­
nia, leptospiral pulmonary hemorrhage 
syndrome (LPHS).
Chronic Disease
• Ophthalmic—anterior uveitis. • Renal/
urologic—chronic kidney disease. 
• Reproductive—abortion; weak puppies; 
linked to feline stillbirth.
• Reported incidence (dogs)—falsely low due 
to inapparent and undiagnosed infections. 
• Prevalence (dogs)—Increasing in urban dogs; 
hospital prevalence increasing since 1990s.
• Worldwide, especially in warm, wet 
climates. • Standing water, neutral or slightly 
alkaline soil promote presence in environ­
ment. • L. canicola  most common worldwide; 
L. icterohaemorrhagiae  most common in 
Australia. • L. bratislava  has yet to be 
confirmed by culture as a serovar in dogs in 
Species
Dogs, rarely cats.Mean Age and Range
• Young dogs without maternal antibodies 
and unvaccinated older dogs more likely to 
exhibit clincal disease. • Dogs with adequate 
antibody titers seldom exhibit clinical disease 
unless exposed to serovar not in vaccine.
N/A
SIGNS
Signs vary with age/immune status, virulence 
of infecting serovar, host response.
Peracute to Subacute Disease
• Fever. • Sore muscles/stiffness. • Weakness, 
lethargy. • Anorexia, vomiting. • Diarrhea—
with/without blood. • Icterus. • Cough, 
dyspnea. • Polyuria/polydipsia (PU/PD) 
progressing to anuria. • Death.
• No apparent illness. • Fever. • PU/PD.
Peracute to Acute Disease
• Tachypnea. • Tachycardia, weak pulses. 
• Hematemesis. • Hematochezia, melena. 
• Epistaxis. • Injected mucous membranes. 
• Widespread petechial and ecchymotic 
hemorrhages. • Reluctance to move, paraspinal 
hyperesthesia, stiff gait. • Conjunctivitis. 
• Rhinitis. • Hematuria. • Mild 
CAUSES
• Dogs— L. canicola , L. icterohaemorrhagiae , 
L. pomona , L. grippotyphosa , L. copenhagenii , 
L. australis , L. autumnalis , L. ballum , and L. 
bataviae .
• Cats— L. canicola , L. grippotyphosa , L. 
pomona , and L. bataviae .
Transmission
• Direct—via urine, post ­abortion discharge, 
fetus, sexual contact (semen). • Indirect—
exposure (via urine) to contaminated 
environment (vegetation, soil, food, water, 
bedding). • Disease in companion animals is 
often result of spillover from diseased wildlife 
maintenance hosts.
Host Factors
• Vaccine—protection is serovar ­specific; may 
not prevent kidney colonization and urine 
shedding; new vaccines available of “subunit” 
type; newer panvalent antigen may cross ­
protect against many serovars. • Outdoor 
animals, hunting dogs—exposure of abraded 
or water ­softened skin increases risk of 
• Warm, moist environment (low ­lying areas, 
rainy season of temperate regions). 
• Temperature range—44.6–50°F (7–10°C) to 93–96°F (34–36°C). • Organism survives 
best in stagnant water with neutral or slightly 
alkaline pH: ◦ 180 days in wet soil; longer in 
standing water. • Dense animal population—
kennels or urban settings. • Exposure to 
rodents, other wildlife (e.g., deer).
  DIAGNOSIS
Subacute to Acute Disease
• Dogs—heartworm disease; hemolytic 
anemias; septicemia; viral infections (canine 
hepatitis, canine herpesvirus); neoplasia; 
trauma; lupus; tick ­borne disease; toxoplas­
mosis; postrenal obstruction; renal toxins 
(e.g., ethylene glycol, aminoglycosides); 
causes of pulmonary interstitial/alveolar 
disease. • Cats—hemotropic mycoplasmosis; 
toxins (e.g., acetaminophen); septicemia; 
feline immunodeficiency virus (FIV) ­ and 
feline leukemia virus (FeLV) ­associated 
diseases; cholangitis; toxoplasmosis; feline 
infectious peritonitis (FIP); neoplasia; 
trauma; postrenal obstruction.
Reproductive/Neonatal Disease
• Dogs—brucellosis, canine distemper, 
herpesviruses. • Cats—FIP , FeLV, 
panleukopenia, herpesvirus, toxoplasmosis, 
salmonellosis.
• CBC—leukocytosis with left shift; 
leukopenia during leptospiremic phase; 
thrombocytopenia. Hematocrit variable with 
hemoconcentration, bleeding, or hemolysis. 
• Chemistry— azotemia; electrolyte 
alterations—depend on degree of renal and 
gastrointestinal dysfunction (hyponatremia, 
hyper/hypokalemia, hypochloremia, 
hyperphosphatemia); hypoalbuminemia; 
elevated hepatic enzyme activities; 
hyperbilirubinemia. • Prolonged 
prothrombin and partial thromboplastin 
times; increased d ­dimer concentrations. 
• Urinalysis—isosthenuria; proteinuria; 
glucosuria.
Serology (Microscopic Agglutination 
Test [MAT])
• Test serum in acute stage and 3–4 weeks 
later (convalescent). • Unvaccinated 
patients—titers initially low (1:100–1:200), 
higher in convalescent sample (1:800–
1:1,600 or higher) if homologous Leptospira  
serovar is tested; several serovars may 
cross ­react in MAT test, especially if high 
titers to one serovar. • Vaccinated patients—
high titers for up to 12–16 weeks post 
vaccination, then drop to <1:400; new 
subunit vaccines—titers rise to ≥1:1,600 for

Canine and Feline, Seventh Edition  829
L12 weeks for serovars L. canicola  and L. 
icterohaemorrhagiae ; titers for other serovars 
(L. pomona  and L. grippotyphosa ) variable. 
• Run acute and convalescent samples at 
same time, if possible.
Darkfield Microscopy of Urine
Fresh urine, often inconclusive.
Fluorescent Antibody Test of Urine
• Leptospira  viability not required; submit 
urine to lab on ice by overnight courier. 
• More conclusive than microscopy.
PCR Test of Urine and Tissue
Only indicates genus Leptospira ; may be 
useful with refinement and validation.
Culture (body fluids or tissues) not practical 
due to fastidiousness of leptospiras; require 
special culture/transport medium.
• Degree of kidney and liver disease depends 
on serovar and host immunity. • Cats—  
generally less severe lesions. • Dogs (acute 
disease)—lungs may be edematous; kidneys 
pale and enlarged; liver enlarged, may be 
friable with multifocal necrosis/hemorrhage; 
gastrointestinal tract may hemorrhage. 
• Warthin–Starry silver stain; immunohisto­
chemistry; fluorescent antibody test on 
formalin ­fixed sections of kidney, liver, fetal/
placental tissue.
  TREATMENT
• Shock—IV, balanced, isotonic replacement 
solution. • Dehydration—IV or oral 
maintenance solutions as indicated. • Severe 
hemorrhage—blood transfusion may be 
indicated. • Oliguria, anuria—restore 
circulating volume; then give intravenous 
osmotic diuretics or tubular diuretics; 
dialysis may be needed. • LPHS—oxygen 
supplementation or mechanical ventilation 
as indicated.
Inform client of zoonotic potential from 
contaminated urine of affected dogs and 
environment.  MEDICATIONS
• Doxycycline 5 mg/kg PO or IV q12h for 2 
weeks; use alone to clear both leptospiremia 
and leptospiruria. • Ampicillin 22 mg/kg IV 
q6–8h (or other penicillins as available); only 
clears leptospiremia; must be followed by 
course of doxycyline.
Doxycycline can cause esophagitis, esophageal 
  FOLLOW-UP
• Vaccine (dogs)—whole ­cell bacterin 
vaccines contain serovars L. canicola/ 
icterohaemorrhagiae  (newer also include L. 
pomona /grippotyphosa ): ◦ Promotes immunity 
to homologous serovars and protection from 
overt clinical disease; may not prevent 
colonization of the kidneys, resulting in 
chronic carrier state. ◦ Serovar ­specific. 
◦ Newer subunit vaccine contains L. pomona , 
L. icterohaemorrhagiae , L. grippotyphosa , and 
L. canicola ; possibly provides protection from 
clinical disease/prevents kidney colonization. 
◦ Bacteria ­induced immunity lasts 6–8 
months and is serovar ­specific. ◦ Revaccinate 
at least yearly. ◦ Vaccinate high ­risk dogs 
(hunter, show dogs, dogs with access to water/
ponds) every 4–6 months, especially in 
endemic areas. • Kennels—strict sanitation to 
avoid contact with infected urine; control 
rodents; monitor/remove carrier dogs until 
treated; isolate infected animals during 
treatment. • Activity—limit access to marshy/  
muddy areas, ponds, low ­lying areas with 
stagnant surface water, heavily irrigated 
pastures; limit access to wildlife. • Environ­
mental contamination—leptospira shedding 
in urine is intermittent; leptospira survive but 
do not multiply in environment; cells survive 
until either drying, UV light exposure, or 
freeze ­thaw has killed the leptospires.
• DIC. • Permanent liver/kidney 
dysfunction. • Uveitis. • Abortion.EXPECTED COURSE AND PROGNOSIS
• Most infections subclinical or chronic. 
• Prognosis guarded for acute severe disease.
Severe clinical disease in young dogs 
(nonvaccinated or lacking maternal 
antibody).
• High—spreads in urine of infected animals. 
• Strict kennel hygiene and disinfection of 
premises.
• Possible abortion. • Antimicrobial 
therapy—consider effect of drug on 
developing fetus.
• DIC = disseminated intravascular 
• FeLV = feline leukemia virus.
• FIP = feline infectious peritonitis.
• FIV = feline immunodeficiency virus.
• LPHS = leptospiral pulmonary hemorrhage 
syndrome.
• MAT = microscopic agglutination test.
• PU/PD = polyuria/polydipsia.
disease.php?name=leptospirosis&lang=en
Reagan KL, Sykes JE. Diagnosis of canine 
leptospirosis. Vet Clin North Am Small 
Anim Pract 2019, 49:719–731.
available online(continued)  Leptospirosis

830  Blackwell’s Five-Minute Veterinary Consult  
LLeukemia, Chronic Lymphocytic
  BASICS
OVERVIEW
• Uncommon, lymphoproliferative disorder. 
• Slowly progressive over months to years. 
• Circulating neoplastic lymphocytes are 
mature and well differentiated. •  May 
originate in spleen or bone marrow.
• More frequent in dog than cat. •  No sex 
predilection reported. •  Dogs—mean age 10 
years (range 1.5–15 years). •  Cats—median 
age 12.5 years (range 5–20 years).
SIGNS
• Nonspecific, often no clinical signs of 
illness. •  Lethargy, decreased appetite, 
chronic weight loss. •  Lymphadenomegaly, 
splenomegaly. •  Fever. •  Polydipsia/polyuria.
Unknown
  DIAGNOSIS
• Lymphoma—may have a leukemic phase 
(stage V). •  Acute lymphoblastic leukemia. 
• Immune-mediated hematologic diseases. 
• Chronic antigenic stimulation (reactive 
lymphocytosis)—ehrlichiosis. •  Acute viral 
infection-associated lymphocytosis.
• Lymphocytosis—range 5,000 to >500,000 
cells/μL; typically small, mature lymphocytes. 
• Larger size cells (intermediate-size or blasts) 
may be observed, especially with progression 
to blast crisis (advanced stage). •  Mild-to-
moderate normocytic, normochromic anemia 
(nonregenerative). •  Normal-to-low platelet 
count (uncommon). •  Normal-to-low 
neutrophil count (uncommon). •  Normal-to-
mildly increased serum globulins.
• Immunophenotyping by flow cytometry 
(peripheral blood) is becoming more common 
practice for classification of leukemias 
(noninvasive)—affords prognostic information. 
• Immunocytochemical staining (bone marrow 
samples), flow cytometry of bone marrow 
aspirates, or PCR for antigen receptor 
rearrangement (PARR) may be useful for 
classification of leukemias. •  Cytologic 
examination (bone marrow aspirate or core 
biopsy) may show high numbers of mature 
lymphocytes (especially B-cell chronic 
lymphocytic leukemia [CLL]); crowding  
out of normal cell lines in advanced stages. •  If 
hyperglobulinemia, serum protein electrophoresis 
to detect monoclonal gammopathy. •  Direct 
Coombs’ test may be positive with secondary immune-mediated hemolytic anemia. 
• Serology for Erlichia canis .
IMAGING
Radiography and ultrasonography may reveal 
splenomegaly or internal lymphadenomegaly.
• Bone marrow aspiration (cytology) or 
marrow biopsy (histopathology) may be used 
for immunophenotyping. •  Lymph node and 
spleen cytology or histopathology may help 
differentiate CLL from leukemic phase of 
lymphoma.
  TREATMENT
• Usually outpatients treated with oral therapy. 
• T reatment should be instituted when patient 
demonstrates clinical signs of illness (including 
weight loss, lethargy), lymphadenomegaly or 
organomegaly, cytopenias, or with lymphocyte 
count above 50,000/ μL. • Consult a 
veterinary oncologist for updates in treatment 
options and regimens.
• Dogs—chlorambucil 6 mg/m2 PO q24h for 
7–14 days; then 3 mg/m2 PO q24h; and 
eventually (maintenance) 2–4 mg/m2 q48h, 
adjusted based on response and chronic 
hematologic tolerability. •  Cats—chlorambu -
cil 2 mg/patient regardless of body weight 
q2–4 days. •  Prednisone 2 mg/kg (up to 
maximum of 60 mg) PO q24h (dogs); 
5–10 mg/cat q24h (cats; use prednisolone); in 
combination with chlorambucil; may be 
tapered or discontinued when lymphocyte 
count normalizes. •  Alternative chemotherapy 
agents and protocols to be considered when 
resistance or blast crisis develops over time—
consult with an oncologist.
Chemotherapy may have toxic side effects; 
seek advice with oncologist before starting 
treatment if you are unfamiliar with cytotoxic 
drugs.
  FOLLOW-UP
Initially, examination of CBC every 2 weeks; 
response to treatment and disease progression.
Chronic chemotherapy-induced 
myelosuppression; may need to alter dosage, 
depending on neutrophil and platelet counts.EXPECTED COURSE AND PROGNOSIS
• Variable course, but eventually progressive 
to blast crisis or becomes resistant to therapy. 
• Median survival time with therapy 
approaches 18 months in dogs with B-cell 
CLL, and surpasses 24 months in dogs with 
T-cell CLL. •  Median survival time with 
therapy in cats was >14 months in one study.
• CLL = chronic lymphocytic leukemia. 
• PARR = PCR for antigen receptor 
rearrangement.
Adam F , Villiers E, Watson S, et al. Clinical 
pathological and epidemiological assessment 
of morphologically and immunologically 
confirmed canine leukemia. Vet Comp Onc 
2009, 7:181–195.
Bromberek JL, Rout ED, Agnew MR, et al. 
Breed distribution and clinical 
characteristics of B cell chronic lymphocytic 
leukemia in dogs. J Vet Intern Med 2016, 
30:215–222.
Campbell MW, Hess PR, Williams LE. 
Chronic lymphocytic leukaemia in the cat: 
18 cases (2000–2010). Vet Comp Oncol 
2013, 11:256–264.
Comazzi S, Gelain ME, Martini V, et al. 
Immunophenotype predicts survival time in 
dogs with chronic lymphocytic leukemia. J 
Vet Intern Med 2011, 25:100–106.
Workman HC, Vernau W. Chronic 
lymphocytic leukemia in dogs and cats: the 
veterinary perspective. Vet Clin North Am 
Small Anim Pract 2003, 33:1379–1399.

Canine and Feline, Seventh Edition  831
LLeukocytosis
  BASICS
General term—white blood cell (WBC) count 
increased above reference interval; nonspecific to 
type of cell. Evaluation of individual leukocyte 
absolute numbers is needed to discern the cellular 
population(s) causing the overall increase in WBC 
count. Neutrophilia is the most common cause of 
a total WBC increase, and a left shift with toxic 
changes (e.g., Döhle bodies, cytoplasmic basophilia, 
foamy cytoplasmic vacuolation, and/or toxic 
granulation) may be present.
One or more of the following mechanisms:
• Inflammation and increased tissue demand 
for leukocytes causing myeloid hyperplasia in 
the bone marrow.
• T ranslocation of cells from the marginating 
pool to the circulating pool of large vessels.
• Altered cytokine production resulting in 
increased release of cells from marrow storage 
pool.
• Decreased migration to tissues.
• Delayed apoptosis.
Chronic inflammation/leukocytosis may lead 
to nonspecific tissue damage and organ 
GENETICS
Leukocyte adhesion deficiency (LAD) is an 
uncommon, autosomal recessive, primary 
immunodeficiency resulting in reduced neutrophil 
adhesion and inability to migrate to tissues.
• Nothing specific for generalized causes.
• LAD reported in Irish setters and a 
domestic longhair cat.
• Young and nervous/anxious animals with a 
physiologic response.
• Rottweilers, Alaskan Malamutes, Siberian 
huskies, and cats with eosinophil dysregula-
tion diseases.
SIGNS
• Animals with leukocytosis may exhibit 
fever, anorexia, weight loss, organomegaly, 
and other signs caused by the primary disease 
process.
• Affected animals with LAD can exhibit 
persistent marked leukocytosis/neutrophilia, 
impaired wound-healing, recurrent infections, 
and/or weight loss.
CAUSES
• Etiologies resulting in increased inflamma-
tory cytokine production include infectious 
or sterile causes, immune-mediated diseases, 
paraneoplastic or inflammatory disease.
• Shifting of neutrophils from the marginat-
ing pool to the circulating pool (measured) 
can be caused by stress or fear.• Increases in circulating leukocytes due to 
decreased margination to the tissues can be 
caused by excessive endogenous corticosteroid 
or in patients with LAD.
• Delayed apoptosis can lead to hyperseg-
mentation of neutrophils.
Neutrophilia
• Mature neutrophil count above reference 
interval.
• Most common—stress/physiologic response 
or inflammation caused by infectious or 
noninfectious conditions.
• Metabolic disease, corticosteroid excess 
(endogenous or exogenous).
• Physiologic (shift) or stress response.
• Tissue necrosis or trauma (surgical or 
other).
• Neoplasia—chronic myelogenous leukemia 
(primary) and secondary to histiocytic 
sarcoma; leiomyosarcoma; lymphoma; and 
mammary, pancreatic, squamous cell, 
bronchogenic, and hepatocellular carcinomas.
Monocytosis
• Monocyte count above reference interval, 
usually accompanies a neutrophilia.
• Most common—corticosteroid-mediated 
stress response (dogs), or chronic inflammatory 
conditions (infectious and noninfectious).
• Metabolic disease, chemotherapeutic drugs.
• Recovery from acute marrow injury.
• Tissue necrosis or trauma.
• Acute or chronic myelomonocytic or 
monocytic leukemia.
Lymphocytosis
• Lymphocyte count above reference interval.
• Most common—physiologic response or 
young (<6 months) age.
• Infectious agents and inflammatory 
• Post vaccine.
• Physiologic (epinephrine-mediated) anxiety, 
excitement, exercise, fright, pain.
• Neoplasia (dogs and cats)—acute or chronic 
lymphocytic leukemia (primary), and 
non-hemic, lymphoma, thymoma.
• Eosinophil count above reference interval.
• Most common—allergic or hypersensitivity 
reaction, inflammation in selected tissues, or 
parasitic infection.
• Hypereosinophilic syndrome.
• Neoplasia—chronic eosinophilic leukemia 
(primary/uncommon), and paraneoplastic 
syndrome (common) associated with 
lymphoma, mast cell tumor, and infrequently 
other neoplasms.
Basophilia
• Basophil count above reference interval.
• Rare cause of a leukocytosis, may accom-
pany an eosinophilia (same differentials 
apply).• Chronic basophilic leukemia (primary/
uncommon) and paraneoplastic syndrome 
associated with chronic myeloid leukemia and 
essential thrombocythemia.
• Breeds predisposed to hyperadrenocorti-
cism, eosinophilic diseases, or immune-  
mediated diseases.
• Geographic areas with specific infectious 
agents.
• Drugs—adenocorticotropic hormone 
(ACTH); catecholamine injections; corticos-
teroids; granulocyte colony-stimulating factor 
(G-CSF); methimazole.
  DIAGNOSIS
Based upon individual leukocyte 
population(s) causing the leukocytosis.
Leukogram Patterns
• Inflammatory leukogram resulting from 
inflammatory cytokines may include one or 
more of the following: neutrophilia, left shift, 
toxic change, monocytosis, eosinophilia, and/
or basophilia.
• Stress leukogram induced by endogenous or 
exogenous corticosteroids presents with a 
neutrophilia without a significant left shift or 
toxic change, monocytosis, lymphopenia, 
and/or eosinopenia (dogs).
• Excitement/physiologic (shift) leukogram 
mediated by catecholamines resulting in a 
neutrophilia without a significant left shift 
and toxicity, lymphocytosis, and/or 
monocytosis.
• Neoplastic leukograms typically involve the 
uncontrolled proliferation of cells, typically 
lymphocytes. Leukemias of other origin 
(neutrophils/monocytes) occur less frequently 
and inflammation should be excluded first. 
Some non-hemic neoplasms can cause a 
paraneoplastic neutrophilia, eosinophilia, 
and/or basophilia.
• With intense inflammation, the neutrophil 
count can increase dramatically into a range 
more commonly seen with leukemia 
(>50,000/ μL), sometimes referred to as a 
“leukemoid reaction.”
• Consider causes of severe inflammation first 
(e.g., pyometra, peritonitis) as chronic 
myeloid leukemia comprising mature 
neutrophils is rare in veterinary medicine.
• CBC with leukocyte differential and 
absolute numbers with morphology review of 
a blood smear.
• Biochemical profile.
• Urinalysis with bacterial culture and 
sensitivity to evaluate for urinary tract 
infection, if indicated.

832  Blackwell’s Five-Minute Veterinary Consult  
LFactors That May Erroneously Alter 
Laboratory Results
Blood smear review may help exclude errors 
in automated cell counting that can occur in 
the presence of nucleated erythrocytes or 
• Culture, serology, and/or PCR for 
• ACTH stimulation test—if clinical concern 
• Coombs’ test, saline agglutination test—if 
suspicion for immune-mediated anemia.
• Flow cytometry—if suspicion for hemic 
neoplasia, immune-mediated disease.
• PCR for antigen receptor rearrangement 
(PARR)—if suspicion for lymphoid 
IMAGING
Radiography and ultrasonography can aid in 
identifying occult site(s) of infection or 
• Bone marrow aspirate or biopsy if 
• Biopsy any masses.
• Organ evaluation, as indicated.
  TREATMENT
• T reatment should be based on the 
identified underlying etiology of the 
• Animals with infectious causes should 
receive appropriate antimicrobial 
• Suitable immunosuppression for immune-
• Patients with extreme leukocytosis 
>50,000/ μL require intensive management, including the possibility of hospitalization 
due to increased risk of mortality.
N/A
 FOLLOW-UP
• Determine if leukocytosis is persistent via 
repeat CBC to exclude physiologic response.
• In patients with extreme leukocytosis, serial 
CBCs every 24 hours, or as indicated, to assess 
the leukocyte response to medical therapy.
• Leukocyte counts decrease after treatment 
of the inciting cause.
• Resolution can vary from a few hours (e.g., 
lymphocytes post stress) to a few days or 
weeks (e.g., inflammatory neutrophilia).
• Extreme leukocytosis >50,000/ μL is 
associated with a poor prognosis and high 
mortality rate; patients with fever and 
neoplasia have the shortest survival times.
Young animals (<6 months) have higher 
lymphocyte counts than adult animals and 
age-appropriate reference intervals are 
Mild leukocytosis characterized by a mature 
neutrophilia may be observed in pregnant 
animals.SYNONYMS
None
SEE ALSO
• Eosinophilia.
• ACTH = adenocorticotropic hormone.
• G-CSF = granulocyte colony-stimulating 
factor.
• LAD = leukocyte adhesion deficiency.
• WBC = white blood cell.
http://eclinpath.com/hematology/leukogram-
changes/leukocytes/
122–176.
Stockham SL, Keeton KS, Szladovits B. 
Clinical assessment of leukocytosis: 
distinguishing leukocytoses caused by 
inflammatory, glucocorticoid, physiologic, 
and leukemic disorders or conditions. Vet 
33:1335–1357.
Thrall MA, Weiser G, Allison RW, Campbell 
TW. Veterinary Hematology and Clinical 
Chemistry. Ames, IA: John Wiley & Sons, 
2012, pp. 118–184.
Author  Sarah S.K. Beatty
Consulting Editor  Melinda S. CamusLeukocytosis  (continued)

Canine and Feline, Seventh Edition  833
L
  BASICS
OVERVIEW
• Neurodegenerative disorder that affects 
the white matter of young adult Rottweilers 
leading to chronic progressive ataxia of the 
limbs.
• The clinical signs are primarily associated to 
involvement of the cervical spinal cord, but 
white matter lesions are also present in the 
brainstem, cerebellum, and subcortical white 
matter.
• Occurs worldwide.
• Probably autosomal recessive inheritance.
Rottweiler—either sex; onset in adult dogs 
1.5–4 years old.
SIGNS
• Insidious, nonpainful, progressive onset.
• Cervical spinal cord signs prevail despite 
widespread demyelinating process.
• Proprioceptive ataxia of the thoracic (delayed 
protraction with overreaching of the limb) and 
pelvic limbs, with upper motor neuron weakness.
• Front limbs are more severely affected than 
hind limbs. Mild asymmetry between right 
and left limbs may be present.
• Nail scuffing in all limbs.
• Proprioceptive positioning and hopping 
delayed to absent in all limbs.
• Spinal reflexes normal to exaggerated.
• Autosomal recessive inheritance suspected.
• Inbreeding.
  DIAGNOSIS
• Cervical compressive lesions such as cervical 
vertebral spondylomyelopathy (wobbler), 
cervical subarachnoid diverticula, fibrotic 
stenosis, spinal cord tumors—difficult to 
differentiate on clinical signs alone; all can have 
an insidious onset; MRI necessary for diagnosis.
• Neuroaxonal dystrophy and distal sensori ­
motor polyneuropathy—neurologic disorders 
reported in Rottweilers; differentiated on the 
basis of neurologic deficits; neuroaxonal 
dystrophy: deficits relate to the cerebellum; 
distal sensorimotor polyneuropathy: tetraparesis 
associated with lower motor neuron signs.
• Discospondylitis, fracture/luxation, inter­
vertebral disc disease—neck pain; disc disease 
rarely seen in large ­breed dogs at a young age.
Normal
• Spinal cervical survey radiographs normal.
• MRI—on T2W transverse images of the 
cervical spine, bilateral and symmetrical 
well­demarcated, ovoid in shape, intra ­axial 
hyperintensities in the white matter of the 
dorsolateral funiculi, extending contiguously 
from the cervicomedullary junction to the 
sixth cervical vertebral body. Symmetrical 
hyperintensities also observed in pyramids 
and ventral aspect of the crus cerebri in the 
brain. No contrast enhancement.
Cerebrospinal fluid (CSF) analysis normal.
• Although the most severe lesion is located 
in the white matter of the cervical spinal cord, 
it extends caudally into the thoracic spinal 
cord and rostrally into the brainstem.
• Macroscopic examination—in the dorsal 
aspect of the lateral funiculi of the cervical 
spinal cord and in the pyramidal tracts of the 
medulla oblongata, presence of well ­
demarcated whitish opaque foci located 
bilaterally and symmetrically, corresponding 
to myelin loss.
• Microscopy—in the cervical spinal cord, 
the lesion affects the cervical spinal cord 
white matter in the dorsal portion of the 
lateral funiculi (dorsal spinocerebellar, lateral 
corticospinal, reticulospinal, and rubrospinal 
tracts). In the brain, the lesion affects the 
pyramidal tracts, crus cerebri, medial 
lemniscus, caudal cerebellar peduncle, 
trapezoid body, spinal tracts of the trigeminal 
nerve, and optic tracts; multifocal lesions are 
also observed in the cerebellar folia.
• The myelin loss exceeds axon loss with 
extensive astrogliosis and astrocytosis. 
Normal ­appearing axons observed in areas of 
severe demyelination.
• Lesion bilateral with some asymmetry.
  TREATMENT
• Outpatient, unless the severity of neurologic 
deficits precludes nursing care at home.
• Activity—whatever can be tolerated.
• Diet—ensure proper intake of food; patient 
may have difficulty reaching the feeding area.
• Neurologic status—slowly and progressively 
deteriorates; eventually, the patient is unable 
to walk or get up.
• Neurologic examination—monitor 
monthly to assess progression.
• Avoid bed sores and urine and fecal scalding 
by keeping the patient on a clean, dry, and 
cushioned pad (e.g., synthetic sheepskin).
• Severe tetraparesis—within 6–12 months 
• Euthanasia—because of severe debility.
• T2W = T2 ­weighted.
Davies DR, Irwin PJ. Degenerative 
neurological and neuromuscular disease in 
young rottweilers. J Small Anim Pract 2003, 
44(9):388–394.
Eagleson JS, Kent M, Platt SR, et al. MRI 
findings in a rottweiler with 
leukoencephalomyelopathy. J Am Anim 
Hosp Assoc 2013, 49:255–261.
Hirschvogel K, Matiasek K, Flatz K, et al. 
Magnetic resonance imaging and genetic 
investigation of a case of Rottweiler 
leukoencephalomyelopathy. BMC Vet Res 
2013, 9:57.
Author  Joane M. ParentLeukoencephalomyelopathy in Rottweilers

834  Blackwell’s Five-Minute Veterinary Consult  
L  BASICS
OVERVIEW
• Plants in the Lilium  and Hemerocallis  
genera—widely used ornamental plants—are 
very toxic to cats; Lilium —Easter lilies, tiger 
lilies, Japanese show lilies, rubrum lilies, 
numerous Lilium  hybrids; Hemerocallis —
daylilies. •  Ingestion of leaves or flowers and, 
potentially, pollen or vase water—results in a 
severe nephrotoxic syndrome; as little as 1–2 
leaves reported to be lethal. •  Toxic principle(s) 
not elucidated but found to be in the 
water-soluble plant fraction.
• Cats—systemic poisoning. •  Dogs—only 
mild gastrointestinal upset, even after 
ingestion of large quantities of plant material. 
• No age or breed predilections noted.
SIGNS
• Sudden onset of vomiting and drooling—
gradually subsides within 4–6 hours. 
• Depression and anorexia—typically within 
12 hours of exposure; both persist throughout 
the syndrome. •  Polyuria and dehydration; 
azotemia by 12–24 hours; progresses to anuric 
renal failure by 24–48 hours. •  Vomiting—
recurs by 36 hours; accompanied by progressive 
weakness. •  Recumbency—by 2–4 days. 
• Death—by 3–7 days post ingestion. •  Severe 
pancreatitis has also been reported but is rare.
• Plants—Easter lilies, tiger lilies, Asiatic 
hybrid lilies, Japanese show lilies, Lilium  
hybrids, daylily; primarily when used in 
cut-flower arrangements or as household 
potted plants. •  All ingestions by cats of plant 
material from the Lilium  and Hemerocallis  
genera should be considered potentially lethal. 
• Primarily indoor cats—predisposed to 
ingestion of newly introduced flowers or plants.
  DIAGNOSIS
Nephrotoxins
• Aspirin and other nonsteroidal anti-
inflammatory drug (NSAIDs). 
• Cholecalciferol (vitamin D3); calcipotriene. 
• Soluble oxalate-containing plants. 
• Ethylene glycol. •  Nephrotoxic antibiotics—  
aminoglycosides. •  Melamine/cyanuric acid 
Systemic Diseases
• Acute presentation of chronic renal failure. 
• Urinary obstruction. •  Immune-mediated renal disease. •  Leptospirosis. 
• Pyelonephritis. •  Lymphoma.
• Stress leukogram. •  Increases in BUN, 
creatinine, phosphorous, and potassium. 
• Creatinine—may be disproportionately 
elevated compared to BUN. •  Increased 
aminotransferase (ALT), and alkaline 
phosphatase (ALP) possible late in disease—
likely secondary to prolonged anorexia and 
hepatic stress. •  Proteinuria, glucosuria, and 
isosthenuria; numerous tubular epithelial 
casts. Early in the syndrome, tubular cell 
detail can be seen in the casts. 
• Crystalluria— not caused by ingestion of 
these plants. •  Increased amylase and lipase 
may occur with very large ingestions.
• If possible, examine plant to verify that it 
has been chewed. •  Have plant positively 
identified by a professional horticulturist or 
other expert if necessary.
• Gross—swollen, edematous kidneys; 
systemic congestion; pancreatic necrosis may 
be seen. •  Histologic—severe acute renal 
tubular necrosis with intact basement 
membranes; mild to severe interstitial edema; 
severe cast formation in the collecting ducts; 
later in the syndrome may note evidence of 
mitotic figures in the remaining tubular 
  TREATMENT
• Early decontamination—lessens duration and 
severity of signs. Inducing emesis may be helpful 
if vomiting has not already occurred. Endoscopy 
has been used to remove plant pieces. Bathe cats 
if pollen is noted on the patient’s face or fur. 
• Fluid therapy—initiation within 18 hours of 
ingestion typically prevents anuric renal failure; 
intra venous balanced crystalloids at 2–3 times 
maintenance for 48–72 hours. •  Anuric renal 
failure—peritoneal or hemodialysis is the only 
effective treatment; 7 days or more of therapy 
has resulted in a return of renal function in a 
few cases but does not guarantee recovery.
• Emetic agents for cats—xylazine 0.44 mg/
kg IM or dexmedetomidine 7 μg/kg IM. 
• Activated charcoal 1–2 g/kg PO. • Cathartic—sorbitol 70% solution 1–2 mL/
kg PO.
• Avoid fluids containing potassium if 
hyperkalemic. •  Avoid drugs eliminated by 
renal clearance. •  Diuretics (mannitol, 
hypertonic fluids, furosemide, thiazides) are 
not effective at initiating urine production 
once anuric renal failure has occurred.
  FOLLOW-UP
• Monitor renal values and electrolytes every 
12–24 hours during treatment with IV fluids. 
• Repeat 2–3 days after discharge, then as 
needed based on results and signs.
• Dehydration from polyuric renal failure is 
required for the disease to progress to anuria. 
• Prevention of dehydration (early fluids)—
prevents the progression of the syndrome to 
anuria. •  Initiation of IV fluids within 18 
hours of exposure and prior to development 
of renal failure carries a good prognosis. 
• Without treatment or if treatment is 
delayed, the mortality rate of lily toxicosis in 
cats is reportedly as high as 100%.
SEE ALSO
drug.
Bennet AJ, Reineke EL. Outcome following 
gastrointestinal tract decontamination and 
intravenous fluid diuresis in cats with 
known lily ingestion: 25 cases (2001–2010). 
242(8):1110–1116.
Hall JO. Lily poisoning. In: Peterson ME, 
Talcott PA, eds., Small Animal Toxicology, 
3rd ed. Philadelphia: W.B. Saunders, 2013, 
pp. 617–620.
Author  Amanda L. Poldoski
acknowledge the prior contribution of Jeffery 
O. Hall.Lily Toxicosis

Canine and Feline, Seventh Edition  835
L  BASICS
OVERVIEW
• Invasive, non-encapsulated, lipoma variant 
that does not metastasize.
• A benign neoplasm that infiltrates soft 
tissues, particularly muscles, and including 
fasciae, tendons, nerves, blood vessels, salivary 
glands, lymph nodes, and joint capsules, and 
occasionally bones.
• Muscle infiltration typically extensive.
• Surgical cure—possible but difficult to 
obtain. Radiation therapy has utility to 
control growth.
• Occurs much less frequently than does 
lipoma.
• Usually middle-aged dogs.
• No breed predilection definitively 
demonstrated; Labrador retrievers possibly 
• May be more common in females than in 
males.
SIGNS
• Large, diffuse, soft tissue mass.
• Clinically appears as localized muscle 
swelling and/or distended abdomen if 
abdominal component.
• Infiltration of pelvic, thigh, shoulder, 
sternal, and lateral cervical musculature most 
common; recent evidence suggests no clear 
site prediction.
Unknown
  DIAGNOSIS
• Soft tissue sarcoma, particularly 
liposarcoma, hemangiopericytoma, 
myxosarcoma, rhabdomyosarcoma, and 
fibrosarcoma.
• Lipoma.
• Intermuscular lipoma.
• Mast cell neoplasia.
Normal
N/A
IMAGING
• Radiography—reveals fat dense tissue 
between soft tissue dense structures.
• CT or MRI—fat-attenuating lesions allow 
adequate discrimination of tumor for surgery 
and/or radiation treatment planning; 
however, differentiation of normal fat from 
infiltrative lipoma can be problematic.DIAGNOSTIC PROCEDURES
• Cytologic examination of aspirate reveals 
mature adipocytes with no cellular or nuclear 
atypia, identical to cells that form adult fat.
• Incisional biopsy can provide definitive 
histologic diagnosis if sufficient tissue 
representation of adipocytes and myocyte 
fibers can be identified.
• Histologic examination—well-differentiated 
adipocytes; may be indistinguishable from 
normal adipose tissue.
• Distinctive feature—tumor infiltration into 
and between muscle bundles and other tissues.
  TREATMENT
• Characteristic invasiveness makes excision 
extremely problematic; difficult to distinguish 
between tumor and normal adipose tissue.
• Poorly defined tumor margins—may 
contribute to the observed high recurrence 
rate after surgical excision.
• 36–50% of patients have recurrence within 
3–16 months, except with limb amputation 
for appendicular tumor.
• Amputation of an affected limb is 
recommended only when quality of life is 
affected; tumor causes little inconvenience 
unless it interferes with movement 
(mechanical lameness), causes pressure-related 
pain, or develops in a vitally important 
anatomic site. However, amputation must be 
performed before growth of proximal extent 
of tumor crosses attainable surgical margin.
External Beam Radiotherapy
• Beneficial for long-term tumor control—
median survival 40 months in a retrospective 
study of 13 dogs, with only 1 dog (7.7%) 
euthanized owing to tumor-related signs (vs. 
26.7% with surgery alone).
• Dogs with measurable disease may only 
have stabilization of the tumor.
• Cytoreductive surgery to microscopic 
disease prior to radiation may result in 
long-term disease control.
• Unlikely to kill mitotically inactive mature 
adipocytes but may inhibit progressive 
infiltration by damaging tumor micro- 
N/A
• Therapeutic recommendations— guided by 
size, anatomic location and quality of life to 
determine whether and when to recommend 
surgery and adjunctive radiation therapy for 
incomplete surgical margins.
• Reevaluations—schedule as dictated by 
tumor growth and choice of therapy.
radiation therapy; consultation with a 
regarding specific, anatomic site-related side 
effects.
• Surgical cure only possible if all affected 
tissues can be removed. Long-term control of 
tumor growth may be attained with external 
beam radiation therapy alone or in combina-
tion with surgery.
• Lack of metastatic potential affords a good 
prognosis if local tumor growth can be 
• If liposarcoma diagnosed, behavior is 
similar to other soft tissue sarcomas, 
therefore consult relevant literature on these 
tumors.
SYNONYMS
Lipomatosis
McEntee MC, Page RL, Mauldin GN, et al. 
Results of irradiation of infiltrative lipoma 
in 13 dogs. Vet Radiol Ultrasound 2000, 
41:554–556.
Consulting Editor  Timothy M. FanLipoma, Infiltrative

836  Blackwell’s Five-Minute Veterinary Consult  
LLiver Fluke Infestation
  BASICS
OVERVIEW
• Flukes reported in cats: Platynosomum 
concinnum  (syn. P . fastosum , P . illiciens ) 
(infection occurs in cats in Florida, Hawaii, 
Puerto Rico, and other tropical–semitropical 
areas); Opisthorchis felineus  (Italy, Eastern 
Europe); Opisthorchis viverrini  (southern 
Vietnam, Thailand, Laos, Malaysia, India); 
Amphimerus pseudofelineus  (the Americas); 
Clonorchis sinensis  (also known as Oriental 
liver fluke of people; northern Vietnam, 
China); Metorchis albidus, M. conjunctus  
(North America, Europe, Russia); Eurytrema 
procyonis  (eastern United States). • Flukes 
reported in dogs: Heterobilharzia americana  
(southeastern United States); Clonorchis 
conjunctus ; Clonorchis sinensis  (China); 
Schistosoma japonicum  (Philippines); 
Schistosoma haematobium  (Zambia); Metorchis 
bilis, and Opisthorchis felineus  (Germany) in 
sled dogs fed a diet including raw fish; 
Opisthorchis viverrini  (southern Vietnam, 
Thailand, Laos, Malaysia, India). 
• Platynosomum concinnum  is the most 
common fluke infecting cats. One report of 
infection in a cat from Ohio and one from 
Illinois. It is the most common trematode 
infection affecting the liver of companion 
pets in North America. • Infestation acquired 
from ingestion of infected intermediate host 
(e.g., lizard or frog). • Estimated 15–85% of 
cats with intermediate host access are infected in 
endemic areas. • Heterobilharzia americana— 
raccoon is the natural definitive host and 
most important reservoir host; dogs can also 
serve as the definitive host.
• Platynosmum concinnum —young (6–24 
months) cat with access to local fauna. 
• Heterobilharzia americana —dogs swimming 
or wading in contaminated freshwater 
sources; young adult dogs more commonly 
affected.
SIGNS
• Cats ( P . concinnum )—depends on severity 
of infection. • Most infected cats lack clinical 
signs. • With severe infestation—jaundice, 
emaciation, anorexia, vomiting, mucoid 
diarrhea, hepatomegaly, abdominal 
distention, malaise, fever. • Dogs ( H. 
americana )—lethargy, weight loss, vomiting, 
diarrhea, inappetence, hypercalcemia, 
P. concinnum
• Adults reside in bile ducts and gallbladder; 
life cycle requires two intermediate hosts and 
tropical or semitropical climate. • Embryonated eggs pass in cat’s feces; 
ingested by first intermediate host (a land 
snail). • Miracidia hatch from eggs in the 
snail penetrating host tissue and develop 
sporocysts. • Mature daughter sporocysts 
emerge from the snail and thereafter are 
ingested by a second intermediate host, 
usually an anole lizard (but also skinks, 
geckos, frogs, and toads); enter bile ducts 
where they reside until host ingested as prey 
by the cat. • Cercariae released in the upper 
digestive tract of the cat; migrate to the bile 
ducts where they mature and shed eggs within 
8 weeks. • Risk factors for infection—tropical 
or subtropical climate; appropriate 
intermediate hosts; access to an outdoor or 
indoor/outdoor environment; successful 
hunting skills; consumption of infected 
intermediate host.
Metorchis conjunctus
• In cats—may infect the liver and biliary 
structures initially causing watery blood-
tinged diarrhea and later evidence of biliary 
tree invasion; eggs are passed in feces 
17 days from initial infection. • Infection 
typically associated with increased liver 
enzyme and may be associated with 
transient eosinophilia.
Heterobilharzia americana
• Eggs containing fully developed miracidium 
are passed in feces of definitive (final) host. In 
fresh water, eggs hatch, release miracidia that 
penetrate snail hosts, where sporocysts 
develop. Cercaria released from snail host 25 
days after infection; these infect vertebrate 
host (dog, human) by skin penetration. 
• Adult flukes develop in liver and migrate to 
mesenteric veins where eggs disseminate to 
various viscera, including liver, pancreas, 
mesenteric lymph nodes, spleen, and 
intestines; there they initiate granulomatous 
inflammation and sclerotic vascular lesions. 
• Healing leads to scar formation and organ 
injury that can result in liver failure and 
gastrointestinal malabsorption. • Eggs appear 
in feces 68 days after infection.
Schistosoma haematobium
Adult fluke and eggs disperse to splanchnic 
organs, including liver and pancreas; in 
portal or hepatic veins eggs and adults 
associate with encapsulated fibrotic granu -
lomatous foci.
  DIAGNOSIS
• Cholangiohepatitis; hepatic lipidosis; bile 
duct carcinoma; hepatic lymphoma; choleliths 
and any disorder causing major bile duct 
occlusion. • In dogs, primary gastrointestinal diseases and neoplasia (lymphoma) may be 
suspected. • Identified by finding trematode 
eggs in feces, rarely observing anechoic ovoid 
structures with echoic center in biliary tree by 
ultrasound, cytologic examination of bile or 
hepatic aspirates; most definitively from 
histopathology of biopsied liver, biliary 
structures, or pancreas.
• CBC—cats: variable; eosinophilia beginning 
3 weeks after infection; persists for months; 
not all infected cats demonstrate eosinophilia; 
dogs: most common findings are lymphopenia 
and mild to marked thrombocytopenia; 
anemia; eosinophilia is uncommon. 
• Biochemistry—cats: high liver enzyme 
activities, especially alanine aminotransferase 
(ALT) and aspartate amino  transferase (AST); 
alkaline phosphatase (ALP) may be normal or 
only slightly increased initially; bilirubin 
usually increased, markedly high in advanced 
cases; dogs: variable elevation in liver enzyme 
activities; hypercalcemia thought to be 
secondary to granulomatous inflammation; 
hypernatremia, hyper  cholesterolemia, hypo- 
or hyperalbuminemia, hyperglobulinemia, 
azotemia. • Bilirubin—cats: increased; 
markedly high in advanced severe disease; 
dogs: usually normal, may be increased. 
• Urinalysis—cats: bilirubinuria.
• Fasting/postprandial bile acid—increased. 
• Fecal examination in cats—noninvasive 
definitive diagnostic test: P . concinnum  eggs 
detected in only 25% of infected cats. • Fecal 
egg retrieval—cats: sedimentation most 
successful; formalin-ether or sodium acetate 
most reliable (demonstrates eightfold more 
eggs than direct fecal examination); dogs: 
sedimentation with saline recommended as 
miracidium will hatch in fresh water making 
identification difficult. Direct saline smear of 
feces may identify eggs. • Feline patients with 
few parasites (one to five flukes) may shed 
only 2–10 eggs/g of feces; eggs may not be 
discovered by fecal testing. • Serial fecal 
examinations may be necessary. 
• Coagulation testing—dogs: prothombin 
time/partial thromboplastin time (PT/PTT) 
may be prolonged; antithrombin III (ATIII) 
decreased. • Parathyroid hormone/parathyroid-
related hormone (PTH/PTHrp)—dogs: 
PTHrp may be elevated in hypercalcemic 
patients.
IMAGING
• Abdominal radiography—cats: may show 
mild hepatomegaly; dogs: may show 
hepatosplenomegaly, lymphadomegaly. 
• Abdominal ultrasonography—cats: 
differentiates biliary obstruction from 
hepatocellular disease; shows one or more of 
the following: (1) biliary obstruction: dilated

Canine and Feline, Seventh Edition  837
Lgallbladder, common bile duct (>2 mm), and 
intrahepatic ducts; (2) gallbladder sediment 
with flukes (oval hypoechoic structures with 
echoic center), mildly thick gallbladder wall 
with a double-layered appearance (cholecystitis); 
(3) hypoechoic hepatic parenchyma with 
prominent hyperechoic portal areas (ducts) 
associated with cholangiohepatitis; dogs: 
heterogeneous parenchyma, ascites, spleno -
megaly, lymphadomegaly, thickened gastric 
and intestinal walls.
• Fecal examination for trematode eggs. 
• Cholecystocentesis—discloses fluke eggs in 
cats. • Liver biopsy (cats and dogs)—reveals 
signs of infection, ova.
Cats
• Gross—liver may appear large and 
yellow-green with dilated bile ducts; may see 
flukes in bile ducts or gallbladder; increased 
size and tortuosity of bile ducts on cut 
section. • Histologic lesions—depend on the 
number of flukes and duration of infestation; 
early stage  (4–6 weeks): enlarged bile ducts and 
periductal areas infiltrated with inflammatory 
cells, especially eosinophils; mid-stage  (4 
months): severe adenomatous hyperplasia of 
bile duct epithelium and coincident 
periductal inflammation; late stage  (6 
months): extensive peribiliary fibrous 
connective tissue that may cause bile duct 
stenosis.
Dogs
• Gross—ulcerative gastritis, submucosal 
edema, red mucosal discoloration along 
intestinal tract, dystrophic mineralization of 
multiple organs. • Histologic lesions—
trematode eggs in multiple organs; 
granulomatous inflammation and fibrosis 
throughout multiple organs; dystrophic 
mineralization of multiple organs.
  TREATMENT
Outpatient vs. inpatient—depends on 
severity of illness.
Inpatient
• Balanced polyionic fluids with 
supplemental potassium chloride 20–40 
mEq/L; as appropriate; based on serum 
electrolytes. • Nutritional support—avoid 
development of hepatic lipidosis; feed 
high-protein calorically dense food and ensure 
food intake; use feeding tubes if needed to 
ensure adequate food intake in inappetent 
cats; rarely, severe clinical signs may require parenteral nutrition; rarely hepatic enceph -
alopathy necessitates protein restriction. • B 
vitamin supplementation—important for 
anorectic and ill cats on fluid therapy; 2 mL 
B-soluble vitamins/L fluids.
• Praziquantel 20 mg/kg SC q24h for 3–5 days 
is treatment of choice for cats; eggs may pass in 
feces for up to 2 months after treat  ment. For 
dogs, varying dosages have been reported. 
Praziquantel at 30 mg/kg PO once and 50 mg/
kg SC once cleared a dog symptomatic for 
H. americana ; more recently 25 mg/kg TID for 
2 days and 3 days either orally or SQ, or 15–20 
mg/kg PO q8h for 1–2 days is also reported. 
Some dogs were also treated concurrently with 
fenbendazole at 50 mg/kg PO q24h for 10 
days. • Prednisolone—initial dose for cats 
showing eosinophilia, significant inflammation 
on biopsy or having severe clinical signs: 1–2 
mg/kg/day for 2–4 weeks; then tapered in 50% 
decrements every 2 weeks. • Ursodeoxycholic 
acid 10–15 mg/kg q24h PO; tablet form and 
divided dose administered with feeding achieves 
best bioavailability; avoid if evidence of 
extrahepatic bile duct obstruction. • Broad-
spectrum antibiotic coverage to protect against 
retrograde biliary tree infection with enteric 
organisms introduced by parasite; infection 
encouraged by fluke death in tissues. 
• Antioxidant therapy—suggested by necro -
inflammatory tissue injury; vitamin E (10 IU/
kg day PO) and S-adenosyl- l-methionine 
(SAMe; Denosyl-SD4 has proven bioavailability 
in cats as a glutathione [GSH] donor): 20 mg/
kg PO daily, enteric coated tablets, until 
liver enzymes normalize. • Antiemetic—
metoclopramide (0.2–0.4 mg/kg PO, SC 
q6–8h or by constant rate infusion 1–2 mg/kg/
day); ondansetron (0.5 mg/kg q12h IV or PO 
30 minutes before feeding); maropitant (1.0 
mg/kg [5 mg/cat] IV, SC or PO once per day; 
maximum of 5 days).
Pregnancy—use caution with drug use.
  FOLLOW-UP
• Monitor clinical signs, appetite, body 
condition and weight, liver enzymes, 
bilirubin, and fecal sedimentation. • Hypercalcemia in dogs usually resolves 
within 36–48 hours after praziquantel 
administration. • Watch for signs of biliary 
tree occlusion after administration of 
praziquantel. • Monitor fecal saline 
sedimentation for clearance of ova in dogs.
• Restrict outdoor access if endemic parasite. 
• Praziquantel prophylaxis—every 3 months; 
for outdoor cats in endemic, tropical climates.
• Death from liver failure; untreated 
symptomatic disease. • Biliary tree 
obstruction. • Pancreatitis. • Pancreatic 
exocrine insufficiency—with chronic 
infection. • Cholangitis/cholangiohepatitis 
(suppurative or nonsuppurative).
Uncomplicated recovery with treatment 
expected in most patients.
None
SEE ALSO
• ATIII = antithrombin III.
• PTHrp = parathyroid-related hormone. 
• SAMe = S-adenosyl-l-methionine.
americana  infections in dogs, J Vet Intern 
Tams TR. Hepatobiliary parasites. In: 
Sherding RG, ed., The Cat: Disease and 
Management. Philadelphia, PA: Saunders, 
1994, pp. 607–611.
acknowledges the prior contribution of Julie 
R. Pembleton-Corbett.(continued)  Liver Fluke Infestation

838  Blackwell’s Five-Minute Veterinary Consult  
L  BASICS
• Urinary tract infection (UTI)—bacterial 
adherence, replication, and persistence within 
the urinary tract associated with clinical signs 
and/or inflammation. •  Sporadic cystitis 
(uncomplicated UTI): lower UTI that occurs 
no more than once every 6 months. 
• Recurrent UTI—UTI that occurs ≥3 times in 
a year, or ≥2 times in 6 months. Subcategories 
include: ◦ Persistent—UTI that fails to resolve 
after appropriate antimicrobial therapy. 
◦ Relapse—UTI that appears to resolve; 
however, subsequent urine cultures confirm 
persistence of the original bacterial isolate. 
◦ Reinfection—UTI resolves with appropriate 
therapy but abnormal urinary defenses allow for 
recolonization of different bacterial species. 
• Subclinical bacteriuria (asymptomatic 
bacteriuria)—bacterial presence within the 
urinary tract not associated with detectable 
clinical signs and/or inflammation.
UTI development is dependent on the 
interplay between bacterial virulence factors 
and impairment of the anatomical, 
functional, environmental, and immunologic 
competency of the host. Most commonly, 
uropathogenic bacteria originate from the 
enteric flora and ascend from the distal 
urogenital tract into the proximal urethra and 
urinary bladder. Colonization may elicit a 
mucosal inflammatory response resulting in 
dysuria, pollakiuria, pyuria, and hematuria.
• Bacteriuria is not equivalent to UTI. 
Current data identifies UTI prevalence given 
predisposing conditions. •  Prevalence of 
bacteriuria in dogs: ◦ With subclinical 
bacteriuria: 2.1–8.9%. ◦ With diabetes 
mellitus: 37%. ◦ With hyperadrenocorticism, 
at diagnosis: 46%. ◦ With thoracolumbar 
intervertebral disc extrusion: 20.0–38.5%. 
◦ With indwelling urinary catheters: 63.8%. 
• Prevalence of bacteriuria in cats: ◦ With 
subclinical bacteriuria: 0.9–28.8%. ◦ With 
lower urinary tract-associated clinical signs: 
3.4–12.0%. ◦ With ureteral calculi: 8.4%. 
◦ With chronic kidney disease: 16.9–29.1%. 
◦ With diabetes mellitus: 12.2–12.8%. 
◦ With perineal urethrostomies: 22%.
N/A
Species
More common in dogs than cats.Breed Predilections
Breed-associated conditions (hyperadreno -
corticism, urolithiasis, etc.) may promote 
• UTIs occur at any age, but are more 
common in older dogs and cats. •  Dogs—
female: mean 7.7 ± 0.1 years; male: mean 8.0 
± 0.1 years. •  Cats—female: mean 11.8 ± 4.4 
years; male: mean 9.8 ± 4.8 years.
• Dogs—female dogs more commonly affected. 
• Cats—female cats are slightly overrepresented.
SIGNS
• Patients may be asymptomatic. •  Pollakiuria, 
dysuria, hematuria, stranguria, inappropriate 
elimination, and excessive licking at or 
discharge from the genitalia may be present. 
• Systemic clinical signs (anorexia, fever) are 
infrequent and suggest complicating factors 
(e.g., pyelonephritis).
• Unremarkable in most animals. •  Abnormalities 
occasionally noted with urinary bladder palpation: 
◦ Stimulation of micturition. ◦ Pain reactions.
CAUSES
• Uropathogenic bacteria commonly 
originate from enteric flora with rare 
hematogenous origins. •  Escherichia coli  is 
the most common bacterial isolate in dogs 
(45–55%) and cats (37.3%). •  Eight species 
of bacteria ( E. coli , Staphylococcus , Proteus , 
Streptococcus , Klebsiella , Enterococcus , 
Pseudomonas , and Corynebacterium ) account 
for approximately 95% of UTIs.
• Immune dysfunction/suppression (e.g., 
hyperadrenocorticism, feline leukemia virus 
[FeLV], feline immunodeficiency virus [FIV]). 
• Nidus for bacterial adherence and harboring 
(e.g., indwelling urinary catheters, uroliths). 
• Altered urine composition (e.g., persistently 
dilute urine, glucosuria). •  Abnormal 
micturition/urine retention (e.g., loss of urethral 
tone, neurologic disease, urethral obstruction). 
• Abnormal anatomy (e.g., ectopic ureters, 
hooded vulva). •  Disrupted urinary tract 
mucosal defenses (e.g., mucosal trauma).
  DIAGNOSIS
• UTI cannot be diagnosed or excluded based on 
the presence/absence of clinical signs. •  Dysuria, 
pollakiuria, hematuria, and stranguria occur with 
lower urinary tract diseases including cystolithiasis, 
urinary tract neoplasia, prostatitis, obstructive 
uropathy, and feline idiopathic cystitis.CBC/BIOCHEMISTRY/URINALYSIS
• CBC and biochemistry are unremarkable. 
• Urinalysis: ◦ Proteinuria and hematuria 
indicate inflammation. ◦ Urine pH >7.5 may 
indicate the presence of urease-producing bacteria 
(Proteus  spp., Staphylococcus  spp., Ureaplasma  
spp., or Corynebacterium  spp.). ◦ Pyuria is 
present in most animals with UTI but is not 
synonymous with infection. ◦ Bacteriuria 
identification increases UTI suspicion. Using a 
modified Wright–Giemsa stain (Diff-Quik) or 
Gram stain can improve bacterial detection.
Urine Culture
• Definitive diagnosis requires aerobic urine 
culture. •  In female dogs with limited antibiotic 
exposure forgoing a urine culture can be justified 
for uncomplicated UTI if the pathogen and local 
susceptibility patterns are known. In male dogs, 
cats, and animals with recurrent UTI urine 
culture is recommended. •  Cystocentesis is the 
gold standard method for collecting urine culture 
specimens. Bacterial growth >103 cfu/mL is 
diagnostic. •  Urine samples obtained by 
catheterization are often contaminated by the 
normal flora of the distal urethra. Bacterial 
growth >104 cfu/mL in male dogs, >105 cfu/mL 
in female dogs, and >103 cfu/mL in cats is 
diagnostic. Indwelling catheters may be colonized 
without concurrent UTI; therefore, sample 
collection from indwelling urinary catheters 
should be avoided. •  Culturing voided 
midstream urine samples should be avoided 
unless other urine collection techniques are 
contraindicated or not possible. •  Urine collected 
from nonsterile surfaces should not be cultured.
Antibiotic Sensitivity Testing
Antibiotic sensitivity is accurately predicted 
by use of the isolate’s “susceptible” vs. 
“resistant” profiles.
IMAGING
Rarely is imaging necessary for uncomplicated 
infections. Radiographs, contrast studies, and 
ultrasound may help to identify recurrent 
UTI-predisposing causes.
Cystoscopy is used in patients with recurrent 
UTI to visualize abnormalities within the 
urinary bladder and urethra including 
uroliths, masses, polyps, ectopic ureters, etc.
N/A
  TREATMENT
Outpatient treatment is appropriate; inpatient 
treatment may be necessary with UTI 
complications or associated conditions (e.g., 
acute pyelonephritis).Lower Urinary Tract Infection, Bacterial

Canine and Feline, Seventh Edition  839
LNURSING CARE
N/A
ACTIVITY
DIET
N/A
N/A
Management of uroliths, polypoid cystitis, 
and infection niduses may require surgical 
• Given the morbidity associated with 
sporadic cystitis, empiric antimicrobial 
treatment is commonly started before 
receiving urine culture results. •  When 
susceptibility data is available, the lowest tier 
antimicrobial should be selected. •  “First-
line” antimicrobials—should be selected 
when possible: ◦ Amoxicillin (11–15 mg/kg 
PO q8h). ◦ T rimethoprim-sulfadiazine 
(TMS) (15 mg/kg PO q12h). ◦ Amoxicillin/
clavulanic acid (12–25 mg/kg PO q12h). 
• “Second-line” antimicrobials—reserved 
for resistant isolates based on culture and 
sensitivity or when patient factors 
prohibit the use of “first-line” therapies: 
◦ Floroquinolones (e.g., marbofloxacin 
2.7–5.5 mg/kg PO q24h; enrofloxacin; 
ciprofloxacin). ◦ Cefovecin (8 mg/kg SC). 
◦ Nitrofurantoin (4.4–5.0 mg/kg PO q8h). 
• “Third-line” antimicrobials—reserved for 
multidrug resistant infections necessitating 
therapeutic intervention: ◦ Amikacin (dogs 
15–30 mg/kg IV or SC q24h; cats 10–14 
mg/kg IV or SC q24h). ◦ Chloramphenicol 
(dogs 40–50 mg/kg PO q8h; cats 12.5–20 
mg/kg [not exceeding 50 mg/cat] PO q12h). 
• Antibiotic treatment of uncomplicated 
infections is recommended for 3–10 days. 
• Recurrent UTI treatment requires a urine 
culture and sensitivity. •  T reatment 
durations are extended for persistent and 
relapse infections (up to 4 weeks). 
• Reinfections are treated as multiple 
uncomplicated infections, however an 
attempt to identify an abnormality in host 
defenses should be pursued.CONTRAINDICATIONS
N/A
Pyelonephritis or prostatitis necessitates 
therapies able to penetrate the respective 
tissues (see Pyelonephritis; Prostatitis and 
Prostatic Abscess).
N/A
ALTERNATE DRUGS
(NSAIDs) may be used cautiously to reduce 
clinical signs in dogs with cystitis while 
awaiting urine culture results. They should 
not be used in dehydrated patients.
  FOLLOW-UP
• For uncomplicated UTIs clinical 
improvement should occur within 48 hours. 
If clinical signs remain for >48 hours, 
complicating factors should be investigated. 
• Complicated UTIs—continue therapy for 
7–10 days beyond resolution of clinical signs, 
pyuria, and bacteriuria. Confirm resolution 
via urine culture 7–10 days after end of 
therapy.
• Diagnosis and control of predisposing 
conditions is the most effective method for 
preventing UTIs. •  Ancillary therapies can be 
considered to prevent recurrence: ◦ Cranberry 
extract may inhibit E. coli  attachment to the 
bladder mucosa. ◦ Methenamine—converted 
into formalin when urine pH is <7.0. 
Concurrent administration of ascorbic acid 
(vitamin C) promotes urinary acidification. 
◦ Prophylactic antibiotics—once-daily 
administration of antibiotics may lengthen 
infection-free intervals; however, multidrug 
resistance is likely in subsequent isolates.
UTIs may lead to pyelonephritis, struvite 
urolith formation, or polypoid cystitis.
Prognosis for patients with uncomplicated 
UTIs is excellent. The prognosis for patients 
with complicated infections is determined by 
successful control or resolution of 
predisposing conditions.  MISCELLANEOUS
• Struvite urolithiasis. •  Polypoid cystitis. 
• Pyelonephritis. •  Prostatitis. 
• Emphysematous cystitis.
Juvenile animals with recurrent UTIs should 
be evaluated for urolithiasis or urinary tract 
N/A
N/A
SYNONYMS
Bacterial cystitis.
SEE ALSO
• Prostatitis and Prostatic Abscess. 
• FIV = feline infectious virus.
drug.
• TMS = trimethoprim-sulfadiazine.
Weese JS, Blondeau JM, Boothe D, et al. 
International Society for Companion 
Animal Infectious Diseases (ISCAID) 
guidelines for the diagnosis and 
management of bacterial urinary tract 
infections in dogs and cats. Vet J 2019, 
247:8–25.
Wood MW. Lower urinary tract infections. 
In: Ettinger SJ, Feldman EC, Cote E, eds., 
8th ed. St. Louis, MO: Saunders, 2016, 
pp. 1992–1996.
Author  Michael W. Wood
acknowledge the prior contribution of Barrak 
M. Pressler.
available online(continued)  Lower Urinary Tract Infection, Bacterial

840  Blackwell’s Five-Minute Veterinary Consult  
L  BASICS
OVERVIEW
• Funguria is usually due to ascending 
infection of normal commensal flora of the 
skin and mucosa, or environmentally 
ubiquitous organisms (primary funguria).
• Candida albicans  is the most common 
isolate; other Candida  spp. are less common, 
and non -Candida  spp. fungi are rare.
• Urinary shedding may occur with systemic 
fungal infections (secondary funguria).
• Organ system affected—renal/urologic.
• German shepherd dogs and female  
dogs are overrepresented in systemic 
SIGNS
• Dysuria, stranguria, and pollakiuria; gross 
hematuria is rare.
• Many animals are asymptomatic.
• Fungal urinary tract infections (UTIs) are 
associated with immunosuppression or 
immunocompromised disease states.
• Suspected risk factors—diabetes mellitus, 
urinary tract stomata (perineal urethrostomy, 
cystotomy tubes, indwelling urinary 
catheters), lower urinary tract disease 
(transitional cell carcinoma, chronic bacterial 
UTI), recent or chronic antibiotic or 
immunosuppressive therapy.
  DIAGNOSIS
• Causes of lower urinary tract disease 
including bacterial UTI, cystolithiasis, sterile 
cystitis, urethritis, and bladder and urethral 
• Primary funguria must be differentiated 
from systemic infections with secondary 
funguria.
• Contamination of urine samples during 
collection may occur in animals with 
cutaneous or mucocutaneous yeast 
• Yeast/fungal elements are often visible 
within urine sediment. Candida  spp. may 
appear as both budding yeast and filamentous 
structures.
• CBC and biochemistry usually 
unremarkable. With renal or systemic 
involvement, abnormalities will reflect those 
organs involved.IMAGING
• Chest radiographs and abdominal ultrasound 
screen for diseases causing immunocompromise.
• Spinal radiographs may show diskospondylitis 
in cases of systemic aspergillosis.
• Candida  spp. grow within 3 days on 
standard blood agar.
• Other fungi grow more slowly and thus will 
not be detected by standard urine culture 
protocols.
• If fungal UTI is suspected or confirmed, 
fungal culture should be requested.
Antifungal Sensitivity Testing
• C. albicans  is usually susceptible to 
fluconazole; antifungal sensitivity testing is 
typically unnecessary.
• Non- albicans  species of Candida  are more 
commonly resistant to fluconazole, and thus 
susceptibility testing should be considered.
• Susceptibility testing should be performed 
on non -Candida  spp. and with persistent 
Candida  spp. UTI despite 4–6 weeks of 
appropriate antifungal therapy.
  TREATMENT
• Identify and correct any risk factors.
• Patients with asymptomatic funguria and 
no risk factors for disease should have a repeat 
urine culture performed prior to starting 
therapy.
• Fluconazole 5–10 mg/kg PO q12h is the 
initial treatment of choice for C. albicans .
• Antifungal therapy for non- C. albicans  spp. 
should be based on susceptibility testing.
• Drugs with poor urinary excretion of active 
drug, such as itraconazole, ketoconazole, 
posaconazole, and voriconazole, are not 
• Patients with persistent infection after 4–8 
weeks of fluconazole may benefit from 
intravesicular infusion of 1% clotrimazole.
• Amphotericin B (intravenous or intra -
vesicular) can be used, but efficacy is 
unknown. Intravenous therapy is primarily 
used for systemic disease.
Intravesicular clotrimazole should be avoided 
in animals with recent bladder surgery or 
urethral trauma.  FOLLOW-UP
• Repeat urine sediment and urine culture 
every 2–3 weeks to confirm treatment 
efficacy. T reatment should be continued for a 
minimum of 4–6 weeks.
• Urine sediment analysis and culture should 
be performed 1 and 2 months after cessation 
• 25% of dogs and cats with candiduria may 
have persistent and asymptomatic infections. 
T reatment should be reserved for 
symptomatic episodes in these patients.
• T ransitional cell carcinoma.
SEE ALSO
• Aspergillosis, Disseminated Invasive.
• Aspergillosis, Nasal.
• Immunodeficiency Disorders, Primary.
• UTI = urinary tract infection.
Jin Y, Lin D. Fungal urinary tract infections 
in the dog and cat: a retrospective study 
(2001–2004). J Am Anim Hosp Assoc 
2005, 41:373–381.
Pressler B. Fungal urinary tract infection. In: 
Bartges J, Polzin DJ, eds., Nephrology and 
Urology of Small Animals. Ames, IA: Wiley 
Blackwell, 2011, pp. 717–724.
Pressler B, Vaden SL, Lane IF , et al. Candida  
spp. urinary tract infections in 13 dogs and 
seven cats: predisposing factors, treatment, 
and outcome. J Am Anim Hosp Assoc 
2003, 39:263–270.
Schultz RM, Johnson EG, Wisner ER, et al. 
Clinicopathologic and diagnostic imaging 
characteristics of systemic aspergillosis in 30 
dogs. J Vet Intern Med 2008, 22:851–859.
M. Pressler.Lower Urinary Tract Infection, Fungal

Canine and Feline, Seventh Edition  841
L  BASICS
• Lumbosacral stenosis refers to narrowing of 
the lumbosacral vertebral canal and/or L7–
sacral intervertebral foramina, causing 
compression of L7, sacral, or caudal nerves.
• Cauda equina syndrome implies pain or 
other clinical signs related to dysfunction of 
these nerves.
• Congenital—abnormal vertebral 
development causing narrowing of the 
lumbosacral vertebral canal. T ransitional 
vertebrae and other malformations are 
common at this site and may contribute to 
(early) disease progression.
• Acquired—bony and soft tissue degenerative 
changes, most commonly affecting the L7 
intervertebral disc, that cause stenosis of the 
vertebral canal and/or intervertebral foramina. 
Specific syndrome of sacral osteochondrosis 
dissecans is recognized in young German 
shepherd dogs and other breeds.
Nervous—specifically nerves from L7 
caudally.
GENETICS
Unknown
Species
• Reasonably common in dogs.
• Uncommonly reported in cats but 
suspected with increasing frequency.
• Congenital—small to medium dogs; border 
collies.
• Acquired—any medium–large dog; often 
suspected in working dogs, so frequently 
German shepherd dogs and Malinois but also 
common in boxers, Rottweilers.
• Congenital—3–8 years.
• Acquired—mean age at onset 6–7 years. 
Sacral osteochondrosis signs often appear  
~1 year old.
• Congenital—none.
• Acquired—male.
SIGNS
• Lumbosacral pain—salient feature; may be 
the only clinical sign; may be evident in 
reluctance to jump or climb stairs. Pain on 
pressure on, or dorsiflexion of, the lumbo­
sacral vertebral column (often also induced 
during extension of hip joints).• Pelvic limb lameness—caused by lumbar 
7th and/or sacral nerve dysfunction; may 
progress to pelvic limb weakness, muscle 
wasting, and postural reaction deficits.
• Urinary and/or fecal incontinence—caused 
by S1–3 nerve dysfunction.
• Abnormal tail carriage, tail weakness or 
paralysis—results from dysfunction of caudal 
nerves.
• Self­inflicted lesions—most often associated 
with congenital lesions or cauda equina 
CAUSES
• Congenital vertebral malformation, 
including transitional vertebrae, or 
osteochondrosis of the cranial sacrum.
• Intervertebral disc herniation (types I  
and II).
• Hypertrophy or hyperplasia of the 
interarcuate ligament.
• Proliferation of the articular facets and/or 
periarticular soft tissues.
• Subluxation at the lumbosacral junction.
• Inflammatory or neoplastic disease of the 
vertebral canal can produce identical clinical 
signs (hence “cauda equina syndrome”).
Dogs with lumbosacral transitional vertebrae, 
especially German shepherd dogs, have 
increased risk to develop the syndrome.
  DIAGNOSIS
• Hip dysplasia or other orthopedic disease 
(notably iliopsoas injury)—distinguish 
via thorough orthopedic examination ± imaging.
• Chronic discospondylitis, osteomyelitis, 
neoplastic disease—cannot be differentiated 
by clinical signs alone.
• Vertebral fractures and subluxations—
acute; characterized by more bilateral signs.
• Localized meningomyelitis or radiculo­
neuritis—usually more diffuse pain.
• Urinalysis—may reveal lower urinary tract 
infection secondary to urinary incontinence, 
or associated with discospondylitis.
If images suggest the need, cerebrospinal fluid 
(CSF) analysis may aid in diagnosing 
inflammatory (or infectious or neoplastic) 
disease.
IMAGING
• Radiology—commonly exhibit spondylosis 
at the lumbosacral junction; narrowing of the 
L7–S1 disc space; ventral displacement of the 
sacrum relative to the lumbar vertebrae; but interpret with caution because all these can be 
observed in clinically normal animals.
• CT and MRI—modalities of choice. 
Apparent abnormalities must be interpreted 
with regard to the whole clinical picture 
because many are also observed in normal 
animals.
• Electromyography—denervation may be 
detected in muscles innervated by the nerves 
L7 to caudal; denervation confirms localiza­
tion of the lesion but is not specific for 
compressive lesions.
• Slowed sciatic–tibial nerve conduction or 
prolongation of F wave latencies may be 
detected.
• May see one or more of the following 
features:
 ◦Type II disc disease with bulging of dorsal 
annulus.
 ◦Hypertrophy of the interarcuate 
ligament.
 ◦Stenosis of the intervertebral foramen by 
soft tissue or bony proliferation compressing 
L7 nerve(s) or as a congenital lesion.
 ◦Ventral displacement of the sacrum in 
relation to lumbar vertebrae.
 ◦Proliferation of articular facets and 
hypertrophy of joint capsule.
 ◦Congenitally shortened pedicles.
 ◦Thickened and sclerotic laminae and 
articular processes.
 ◦Various vertebral malformations (not 
only transitional vertebrae).
• Cauda equina syndrome can also be 
associated with neoplasia, inflammation, 
  TREATMENT
Urinary incontinence—inpatient for initial 
Urinary incontinence—manual expression or 
catheterize the bladder until adequate 
voluntary control returns; monitor for urinary 
tract infection and administer appropriate 
antibiotics following culture and sensitivity.
ACTIVITY
• Nonsurgical treatment—confinement and 
restricted leash walks, alone or combined with 
systemic anti ­inflammatory drugs or analgesics, 
or epidural injection of corticosteroids, 
frequently alleviate pain; clinical signs may 
return with increasing levels of exercise.
• If treated surgically, restrict for 6–12 weeks; 
then gradual return to athletic function.Lumbosacral Stenosis and Cauda Equina Syndrome

842  Blackwell’s Five-Minute Veterinary Consult  
LDIET
Avoid obesity; excess weight increases 
biomechanical stress on the spine.
• Inform client that there may be progressive 
neurologic impairment of the pelvic limbs, 
urinary and fecal incontinence, and paralysis 
of the tail.
• Inform client that pelvic limb lameness and 
self­inflicted lesions result from pain associated 
with nerve root irritation and/or compression.
• Discuss surgical treatment, which is 
appropriate for cases with severe pain and 
may be suitable for cases with neurologic 
deficits (especially incontinence, which may 
be difficult to reverse).
• Medical management is frequently 
successful for animals with mild pain and/or 
mild neurologic deficits only.
Several options, each focused on alleviating 
the specific source of the problems defined by 
imaging; dorsal laminectomy, lateral 
foraminotomy, or fixation–fusion may all be 
effective in specifically selected cases.
• NSAIDs—e.g., carprofen 2 mg/kg q12h for 
5–7 days then reducing doses until PRN.
• Gabapentin—frequently used at ~20–30 
mg/kg q8h and may be effective (side effect: 
sedation; dizziness reported in humans).
• Epidural corticosteroid—methylprednisolone 
actetate 1 mg/kg ( <0.5 mL total volume).
N/A
  FOLLOW-UP
N/A
• Syndrome progression, increasingly severe 
• Seroma formation—frequent sequela to 
surgery; can be effectively managed by cage 
rest and surgical drainage. Prevent by careful 
soft tissue closure.• Adhesions between nerves and surrounding 
soft tissues after surgery.
• Recurrence of clinical signs following 
medical (commonly) or surgical (less 
commonly) intervention.
• Failure of fixation–fusion implant.
• Fracture of articular process after excessive 
lateral bone excision at surgery.
• Infection (especially if an implant is used 
for surgery).
• Vary with the severity of neurologic injury.
• Majority are successfully managed 
medically, but need to ensure outcome 
matches requirements for dog’s way of life; 
surgery remains an option.
• If low lumbar pain and mild neurologic 
deficits—good prognosis after surgery; 
70–80% have an excellent or good outcome.
• If fecal and urinary incontinence—guarded 
Lower urinary tract infections frequently 
accompany urinary incontinence.
• If a lumbosacral transitional vertebra is 
present, syndrome may develop 1–2 years 
earlier than the average dog.
• Older large ­breed dogs may have 
concomitant diseases that also cause 
neurologic deficits: type II disc protrusions at 
other sites, degenerative peripheral nerve 
disease (especially Labrador retrievers), 
degenerative myelopathy (especially German 
shepherd dogs).
SYNONYMS
• Lumbosacral malarticulation or 
• Lumbosacral spondylolisthesis.
• Lumbosacral spondylopathy.
SEE ALSO
• Intervertebral Disc Disease—Cats.
• Intervertebral Disc Disease, Thoracolumbar.
drug.INTERNET RESOURCES
http://veterinarymedicine.dvm360.com/
vetmed/Medicine/Degenerative ­
lumbosacralstenosis ­in­dogs/Article Standard/
Article/detail/169902
De Risio L, Sharp NJ, Olby NJ, et al. 
Predictors of outcome after dorsal 
decompressive laminectomy for 
degenerative lumbosacral stenosis in dogs: 
69 cases (1987–1997). J Am Vet Med Assoc 
2001, 219(5):624–628.
Janssens L, Beosier Y, Daems R. Lumbosacral 
degenerative stenosis in the dog. The results 
of epidural infiltration with 
methylprednisolone acetate: a retrospective 
study. Vet Comp Orthop T raumatol 2009, 
22(6):486–491.
Jeffery ND, Barker A, Harcourt ­Brown T. 
What progress has been made in the 
understanding and treatment of 
degenerative lumbosacral stenosis in dogs 
during the past 30 years? Vet J 2014, 
201(1):9–14.
Jones JC, Banfield CM, Ward DL. 
Association between postoperative outcome 
and results of magnetic resonance imaging 
and computed tomography in working dogs 
with degenerative lumbosacral stenosis. 
J Am Vet Med Assoc 2000, 
216(11):1769–1774.
Linn L, Bartels K, Rochat M, et al. 
Lumbosacral stenosis in 29 military working 
dogs: Epidemiologic findings and outcome 
after surgical intervention (1990–1999). 
Vet Surg 2003, 32:21–29.
Meij BP , Bergknut N. Degenerative 
lumbosacral stenosis in dogs. Vet Clin 
North Am Small Anim Pract 2010, 
40(5):983–1009.
Suwankong N, Voorhout G, Hazewinkle HA, 
Meij BP . Agreement between computed 
tomography, magnetic resonance imaging, 
and surgical findings in dogs with 
degenerative lumbosacral stenosis. J Am Vet 
Med Assoc 2006, 229(12):1924–1929.
Author  Nick D. Jeffery
available onlineLumbosacral Stenosis and Cauda Equina Syndrome  (continued)

Canine and Feline, Seventh Edition  843
L  BASICS
OVERVIEW
• T wisting of lung lobe(s) at the hilus with 
occlusion or narrowing of the bronchus, 
lymphatics, vein, and (finally) arteries. 
• Affected lobes—right middle lobe most 
commonly affected (especially in large dogs) 
with preexisting pleural effusion; other lobes 
can twist singly or in pairs. Occasionally 
torsion occurs in midlobar area. Pugs are 
very commonly affected, with the left cranial 
lobe most common. •  Initially, the lobe 
becomes engorged with blood and enlarges; 
infarction and necrosis may follow; 
hemorrhagic pleural effusion typically 
develops.
• Dogs and less commonly cats. •  Pugs are 
most commonly affected, although any dog 
may be affected. •  Large-breed dogs more 
commonly have pleural effusion first, and 
then develop torsion. •  Afghan hounds were 
initially reported as commonly affected due to 
chylothorax, but this is rarely seen. •  Any 
age. •  More common in males.
SIGNS
• Tachypnea, acute or chronic respiratory 
distress. •  Lethargy. •  Anorexia. •  Fever. 
• Pain. •  Orthopnea. •  Cough, hemoptysis. 
• Retching. •  Tachycardia. •  Pale mucous 
membranes. •  Cyanosis.
• Inconsistently found with preexisting 
conditions (e.g., trauma, neoplasia, and 
chylothorax; asthma/bronchitis in the cat). 
Atelectasis and or pleural effusion seem to be 
predisposing factors. •  Thoracic or diaphrag -
matic surgery. •  Spontaneous or idiopathic.
  DIAGNOSIS
• Pulmonary contusion or atelectasis. 
• Diaphragmatic hernia. •  Pulmonary 
abscess or infarction. •  Neoplasia. 
• Coagulopathy. •  Pneumonia, 
embolization, or thrombosis. •  Congestive 
heart failure. •  Pleural effusion and 
compression atelectasis. •  Fungal or 
foreign body granuloma. •  Lobar 
consolidation or bronchial obstruction 
from a foreign body.
Nonspecific abnormalities.OTHER LABORATORY TESTS
Fluid analysis—pleural effusion can be 
hemorrhagic; with chronicity or preexisting 
effusions; the effusion may be a modified 
transudate or chylous.
IMAGING
• Opacification of affected lobe with loss 
of visible lobar vessels and truncation of 
bronchus. •  Initially may reveal air broncho-
grams with proximal narrowing or disorienta-
tion of the torsed bronchus. Small gas 
bubbles with “sponge appearance” can be 
scattered throughout affected lobe (vesicular 
gas pattern); seen in 87% of one series. 
• Progressive pleural effusion—suggested by 
ventral leafing and interlobar fissure lines. 
• Consolidation and occasional swelling of 
the torsed lobe with possible displacement or 
rotation of the heart, trachea, or carina. 
Mediastinal shift can be contralateral or 
ipsilateral. Other lobes can be displaced. 
• Thoracentesis provides therapeutic benefits 
and can improve visualization of intrathoracic 
• Thoracic ultrasound prior to fluid removal 
often allows better resolution of internal 
structures. •  Hypoechoic periphery with 
scattered reverberating foci (bronchial 
cartilage) centrally. •  Rounded edges of lobes.
CT
Very useful for confirmation of diagnosis.
• Thoracentesis—obtain pleural fluid for 
analysis (modified transudate, exudate, 
hemorrhage, or chylous effusion possible). 
• Bronchoscopy—may reveal occlusion or 
twist of the associated bronchus. •  Surgical 
exploration—for definitive diagnosis and 
  TREATMENT
• Thoracentesis or chest tube placement as 
needed. •  Intravenous fluid administration 
for support. •  Administer oxygen and treat 
for shock—when indicated. •  Anesthesia—
requires adequate ventilatory support; 
carefully monitor patient. •  Surgical removal 
of the involved lobe(s)—only effective 
treatment; do not untwist lobe and attempt 
to salvage—may lead to recurrence or 
necrosis; in situ ligation of the vessels or 
clamping with noncrushing forceps has been 
advocated to avoid reperfusion problems such 
as acidosis; consider use of surgical stapling 
device; closely inspect remaining thoracic structures for any abnormalities; perform 
culture and pathologic examination of excised 
specimen. •  Post surgery—monitoring; 
supportive care; tube drainage. Torsion of a 
second lung lobe may occur.
• Antibiotics—perioperatively. •  Pain 
control.
N/A
  FOLLOW-UP
• Observe for recurrence of pleural effusion. 
• Reexpansion pulmonary edema—can be a 
serious problem (especially in cats) if large 
volumes of pleural fluid are withdrawn 
quickly or if chronically compressed lungs are 
acutely inflated at surgery. •  Thoracic 
radiographs—before discharge; as needed 
thereafter. •  Prognosis—fair to good if no 
underlying abnormality remains.
Benavides KL, Rozanski EA, Oura TJ. Lung 
lobe torsion in 35 dogs and 4 cats. Can Vet 
J. 2019, 60(1):60–66.
D’Anjou M, Tidwell AS, Hecht S. 
Radiographic diagnosis of lung lobe torsion. 
Vet Radiol Ultrasound 2005, 46:478–484.
Park KM, Grimes JA, Wallace ML, et al. Lung 
lobe torsion in dogs: 52 cases (2005–2017). 
Vet Surg 2018, 47(8):1002–1008.
Wainberg SH, Brisson BA, Reabel SN, et al. 
Evaluation of risk factors for mortality in 
dogs with lung lobe torsion: a retrospective 
study of 66 dogs (2000–2015). Can Vet J 
2019, 60(2):167–173.
Consulting Editor  Elizabeth RozanskiLung Lobe Torsion

844  Blackwell’s Five-Minute Veterinary Consult  
L  BASICS
OVERVIEW
• Considered to be a relatively benign variant 
of systemic lupus erythematosus (SLE). 
• Divided into facial discoid lupus erythema-
tosus (FDLE) and generalized DLE (GDLE). 
• FDLE is one of the most common immune-  
mediated skin diseases in dogs. •  FDLE 
predominantly involves the nasal planum, 
face, and ears. •  GDLE—lesions progress 
beyond the head.
• Dogs and cats. •  Very uncommon in cats. 
• FDLE—collie, German shepherd dog, 
Siberian husky, Shetland sheepdog, Alaskan 
Malamute, chow chow, and their crosses. 
• GDLE—German shepherd dog and 
Chinese crested (predominantly). •  FDLE—
no age predilection; GDLE—older dogs.
SIGNS
FDLE
• Initial depigmentation of nasal planum 
and/or lips progresses to erosions and 
ulcerations. •  Loss of normal “cobblestone” 
architecture of the nasal planum. •  Tissue 
loss and scarring can occur. •  Chronic lesions 
are fragile and may easily bleed; severe 
hemorrhage associated with arteriole damage. 
• May involve pinnae and periocular region.
GDLE
• Lesion behind the neck and/or on 
mucocutaneous junctions. •  Initial lesion—
annular hyperpigmented plaques with adherent 
crust, follicular plugging and central alopecia. 
• Advanced lesions—reticulated patterns of 
hyperpigmentation or hyper  trophic scars.
• Actinic radiation may alter antigenic nature 
of keratinocytes. •  Seasonal and geographic 
exacerbation.
  DIAGNOSIS
Major Considerations
• Other immune-mediated diseases (pemphi-
gus foliaceus, pemphigus erythematosus, SLE, 
ischemic dermatitis, vasculitis). •  Drug 
reaction. •  Dermatomyositis. •  Nasal 
dermatophytosis. •  Mucocutaneous 
pyoderma. •  Insect bite hypersensitivity.
Other (Rare) Considerations
• Contact allergy. •  Zinc-responsive 
dermatosis. •  T rauma. •  Superficial 
necrolytic dermatitis. •  Epitheliotropic 
lymphoma. •  Squamous cell carcinoma.CBC/BIOCHEMISTRY/URINALYSIS
Normal unless due to an underlying cause.
Antinuclear antibody (ANA), LE preparation, 
and Coombs’ tests—usually normal or 
negative except in SLE.
• Biopsy and histopathology will differentiate 
DLE from most other disorders; may be 
complicated by untreated mucocutaneous 
pyoderma. •  Biopsy early lesions—depig-
mented areas, mild erosions, or mildly crusted 
lesions.
Interface-lichenoid dermatitis with prominent 
basal cell apoptosis, varying degrees of 
epidermal atrophy, and pigment incontinence;. 
chronic lesions may include scarring.
  TREATMENT
• FDLE—good prognosis; may be 
disfiguring. •  GDLE—guarded prognosis; 
depends on response to therapy. •  Avoid 
sunlight/apply sunblock.
• Topical therapy (FDLE): 
◦ Glucocorticosteroids—potent fluorinated 
product initially; less potent product later if 
possible (q24h for 14 days; then q48–72h). 
◦ Tacrolimus ointment (0.1%) q12–24h 
initially then taper to q24–72h once in 
remission. ◦ Use a soft muzzle for 10 minutes 
after applying topical therapy to prevent 
medication removal by the patient.
• Systemic therapy (GDLE; severe FDLE): 
◦ Tetracycline and niacinamide—250 mg 
each PO q8h for dogs <10 kg; 500 mg PO 
q8h for larger dogs (alternatives include 
doxycycline 10 mg/kg PO q24h and 
minocycline 5 mg/kg PO q12h). 
◦ Prednisolone—2–4 mg/kg/day either solely 
or in combination with azathioprine 2 mg/kg 
PO q48h; taper prednisone to 0.5–1 mg/kg 
PO q48h for long-term maintenance. 
◦ Cyclosporine—5–10 mg/kg PO q24h as 
alternative immunosuppressive therapy.
• Systemic antibiotic treatment for 3–4 weeks 
prior to systemic immunosuppressive therapy 
to differentiate from mucocutaneous 
pyoderma. •  Vitamin E—10–20 IU/kg PO 
q12h may help reduce inflammation and 
protect the skin. •  Hydroxychloroquine— 
5 mg/kg q24h; antimalarial drug that has 
been used in human cases.  FOLLOW-UP
• Recheck 4 weeks after initiating treatment 
to evaluate for clinical response. •  CBC and 
biochemistry—every 12 months (topical 
therapy); every 3–6 months (systemic 
therapy). •  Azathioprine—CBC and platelet 
counts every 2 weeks for the first month, then 
every 3–6 months.
Affected animals should avoid UV light 
exposure.
• Scarring. •  Secondary pyoderma. 
• Hemorrhage. •  Disfigurement.
• FDLE—progressive but not usually 
life-threatening if left untreated. •  With 
proper treatment, expect remission in 
majority of cases. •  GDLE—prognosis is 
more guarded.
• FDLE = facial discoid lupus erythematosus.
• GDLE = generalized discoid lupus 
erythematosus.
• LE = lupus erythematosus.
Banovic F . Canine cutaneous lupus 
erythematosus: newly discovered variants. 
Vet Clin Small Anim 2019, 49:37–45.
Thierry O, Linder KE, Banovic F . Cutaneous 
lupus erythematosus in the dogs: a 
comprehensive review. BMC Vet Res 2018, 
14:132.
ResnickLupus Erythematosus, Cutaneous (Discoid)

Canine and Feline, Seventh Edition  845
L  BASICS
A systemic autoimmune disease characterized 
by the formation of antibodies against a wide 
array of self-antigens. Pathogenic antibodies, 
circulating immune complexes, and auto -
reactive T-cells are the primary mediators of 
tissue injury.
• Antigen–antibody complexes are formed 
and deposited in a variety of sites, including 
blood vessels, glomeruli, synovial membranes, 
choroid plexus, and skin (type III hyper- 
• Antibodies directed against a broad range of 
membrane, cytoplasmic, and nuclear antigens 
are produced, resulting in direct cytotoxic 
damage (type II hypersensitivity).
• Production of autoreactive T-cells causes 
cell-mediated damage (type IV hypersensitivity).
• Tissue injury is caused by immune-complex 
mediated activation of complement, 
infiltration of inflammatory cells, and direct 
cytotoxicity of autoantibodies against 
membrane-bound antigens.
• Clinical manifestations depend on 
localization of the immune complexes and 
specificity of the autoantibodies.
• Genetic, environmental, pharmacologic, 
and infectious factors may be triggers.
• Musculoskeletal—deposition of immune 
complexes in synovial membranes.
• Skin/exocrine—deposition of immune 
complexes in the skin.
• Renal/urologic—immune-complex 
• Hemic/lymphatic/immune—auto  antibodies 
against red blood cells (RBCs), leukocytes, 
platelets, and bone marrow precursors.
• Other organ systems—associated with 
deposition of immune complexes or 
GENETICS
• In dogs, SLE has been positively associated 
with the presence of dog leukocyte antigen 
(DLA) A7 and negatively associated with the 
presence of DLA A1 and B5. Decreased 
serum IgA has been reported as a predisposing 
factor for SLE in dogs.
• An immune-mediated disease in the Nova 
Scotia duck tolling retriever characterized by 
immune-mediated arthropathy and steroid-
responsive meningitis–arteritis has been 
reported and is termed SLE-related disease in 
this breed.
Uncommon in dog, rare in cat.SIGNALMENT
Species
Dog and cat—male dogs overrepresented.
• Medium to large breeds; breed predis -
positions reported for the Finnish spitz, 
German Shepherd dog, Shetland sheepdog, 
collie, beagle, and poodle.
• Purebred cats, particularly Siamese and 
Persians, may be at increased risk.
Mean age 5 years; range 6 months to 13 
years.
SIGNS
• Onset of clinical signs may be acute or 
insidious with waxing and waning course, 
and different clinical manifestations may 
occur sequentially:
 ◦Lethargy/weakness.
 ◦Anorexia.
 ◦Shifting-leg lameness.
 ◦Skin lesions.
• Swollen and/or painful joints are the major 
presenting sign. Joints are swollen but not 
deformed (nonerosive).
• Symmetric or focal skin lesions—erythema, 
scaling, ulceration, depigmentation, vesicles, 
ulcerated or draining nodules, and/or alopecia.
• Ulceration of mucocutaneous junctions and 
oral mucosa.
• Persistent or cyclic fever—especially in the 
acute phase.
• Lymphadenopathy.
• Muscle pain or atrophy.
CAUSES
Definitive cause not identified. T suppressor 
cells may be defective.
Exposure to UV light may exacerbate 
  DIAGNOSIS
• Major signs—polyarthritis, 
glomerulonephritis, consistent dermatologic 
lesions, hemolytic anemia, thrombocytopenia, 
polymyositis, leukopenia.
• Minor signs—fever of unknown origin, oral 
ulcers, peripheral lymphadenopathy, pleuritis, 
pericarditis, myocarditis, neurologic 
• Definitive diagnosis—positive antinuclear 
antibody (ANA) or lupus erythematosus (LE) 
test (or both), and two major signs or one 
major and two minor signs.• Probable diagnosis—positive ANA or LE 
test (or both), and one major sign or two 
minor signs.
• Infectious diseases (e.g., tick-borne disease, 
septic arthritis).
• Immune-mediated polyarthropathy.
• CBC—anemia, leukopenia, leukocytosis, 
or thrombocytopenia; anemia may be 
moderate and nonregenerative or severe 
and regene  rative (hemolytic).
• Biochemistry—results vary widely, 
depending on the organ(s) affected.
• Urinalysis—repeatable elevated 
protein:creatinine ratio (>1) with benign 
sediment and negative culture.
• ANA test—detects antibodies directed 
against nuclear antigens. False positive and 
false negatives occur.
• LE test on synovial fluid—identifies 
phagocytized nuclear material within 
neutrophils and macrophages; time- 
consuming.
• Direct antiglobulin (Coombs’) test—
identifies complement or antibody on the 
surface of RBCs; test should only be run in 
patients with anemia.
IMAGING
• Radiographs of affected joints reveal soft- 
tissue swelling consistent with nonerosive 
arthritis.
• Thoracic and abdominal radiographs may 
demonstrate hepatomegaly or splenomegaly.
• Arthrocentesis—high cell count with 
nondegenerate neutrophils and monocytes 
and low viscosity are characteristic findings.
• Bacterial culture of synovial fluid—negative.
• Blood culture in animals with fever—negative.
• Skin biopsy—in patients with skin lesions; 
save specimen in 10% buffered formalin (for 
histologic examination) and Michel’s solution 
(for immunofluorescence).
• Nonerosive polyarthritis with infiltrations 
of synovial membrane by neutrophils and 
lymphocytes; no pannus formation.
• Membranous or membranoproliferative 
• Mononuclear interface dermatitis with 
hydropic degeneration of keratinocytes and 
eosinophilic round bodies representing 
apoptotic basal keratinocytes.
• Vasculitis and panniculitis in some patients.
• Deposition of immune complexes along the 
basement membrane of the dermal–epidermal 
junction (detected by immunofluorescence).
• Vasculitis may be seen in any organ.Lupus Erythematosus, Systemic (SLE)

846  Blackwell’s Five-Minute Veterinary Consult  
L• Reactive lymphoid hyperplasia in the 
lymph nodes and spleen.
  TREATMENT
• Hospitalization—may be necessary for 
initial management.
• Outpatient management—often possible.
Supportive care varies with systems affected.
ACTIVITY
• Enforced rest—during episodes of acute 
• Avoid sunlight if photosensitization 
DIET
Restricted protein, high-quality protein diet 
with n-3 fatty acid supplementation in 
animals with glomerulonephritis.
• Progressive, unpredictable disease course .
• Need for long-term, immunosuppressive 
therapy and its side effects.
• Heritability of the disease.
• Corticosteroids—to control the abnormal 
immune response and reduce inflammation 
(e.g., prednisone 1–2.2 mg/kg/day PO). 
Consider alternative steroids (equivalent 
doses) in cats; e.g., prednisolone, 
dexamethasone, triamcinolone, 
methylprednisolone.
• Cytotoxic immunosuppressive drugs—add 
when prednisone fails to improve the 
condition after 7–10 days or if the patient is 
steroid intolerant.
• Azathioprine (dogs only) 2 mg/kg PO q24h 
until remission, then q48h.
• Chlorambucil (cats and dogs) 0.1–0.2 mg/kg 
PO q24h initially, then q48h.
• Cyclosporine – microemulsion (e.g., 
Atopica); dogs: 5–10 mg/kg/day PO, divided 
twice daily; cats: 0.5–3 mg/kg PO q12h.
• Mycophenolate mofetil (dogs) 10 mg/kg PO q12h until remission, then taper.
• Gradually taper doses (no more often than 
every 3–4 weeks) once remission is achieved.
• Azathioprine should be avoided in cats.
• Azathioprine and chlorambucil may cause 
bone marrow suppression.
• Cyclosporine may cause gastrointestinal 
upset, papillomatosis, and gingival 
• Mycophenolate mofetil may cause GI 
upset, lymphopenia.
• T reatment with immunosuppressive drugs 
can increase the risk of severe infection.
• Concurrent use of aspirin (or other 
nonsteroidal anti-inflammotory drugs) and 
prednisone is contraindicated.
• Cyclosporine may have multiple drug 
interactions due to inhibition of cytochrome 
P450 enzymes.
• Levamisole: dogs, 2–5 mg/kg PO, EOD for 
4 months (maximum 150 mg per patient) 
combined with prednisone 0.5–1.0 mg/kg 
PO q12h. The prednisone is tapered over  
1–2 months and the levamisole continued for 
4 months.
• Other immunosuppressive drugs can be 
considered depending upon the clinical 
manifestations exhibited (leflunomide for 
immune-mediated hemolytic anemia, 
polyarthritis, and myasthenia gravis, topical 
tacrolimus for skin lesions).
  FOLLOW-UP
• Physical examination – weekly.
• CBC and biochemical analysis—to monitor 
for side effects of therapeutics; day 7 then 
every 2–4 weeks.
• ANA—often remains elevated during 
remission but may fall as patient improves.
• Renal failure and nephrotic syndrome 
secondary to glomerulonephritis.• Bronchopneumonia, urinary tract infection, 
or sepsis secondary to immunosuppression.
Prognosis is guarded. The presence of 
hemolytic anemia and glomerulonephritis 
and the development of bacterial infection 
warrant a poor prognosis. In up to 40% of 
cases, death occurs during the first year of 
treatment as a result of renal failure, poor 
response to therapy, drug complications, or 
secondary systemic infections.
The use of cytotoxic immunosuppressive 
drugs in pregnant animals is contraindicated.
SEE ALSO
• Polyarthritis, Nonerosive, Immune-
Mediated, Dogs.
• Thrombocytopenia, Primary Immune- 
Mediated.
• DLA = dog leukocyte antigen.
Berent A, Cerundolo R. Systemic lupus 
erythematosus. Compend Stand Care 
Emerg Crit Care Med 2005, 7:7–11.
Chabanne L, Fournel C, Monier JC. Canine 
systemic lupus erythematosus: part 2: 
diagnosis and treatment. Compendium 
1999, 21:402–421.
Gross TL, Ihrke PJ, Walder EJ, Affolter VK. 
Skin Diseases of the Dog and Cat: Clinical 
and Histopathological Diagnosis, 2nd ed. 
Ames, IA. Blackwell Science, 2005, 
pp. 55–57.
Stone M. Systemic lupus erythematosus. In: 
Ettinger S, Feldman E, eds., Textbook of 
Veterinary Internal Medicine, 7th ed. Vol. 
1. St. Louis, MO: Saunders Elsevier, 2009, 
pp. 783–787.
Author  Fiona L. Bateman
Consulting Editor  Melinda S. CamusLupus Erythematosus, Systemic (SLE)  (continued)

Canine and Feline, Seventh Edition  847
L  BASICS
• One of the most common tick-transmitted 
zoonotic diseases in the world.
• Caused by spirochetes of the Borrelia 
burgdorferi  (Bb) sensu lato complex.
• Most seropositive dogs are nonclinical; 
5% may show Lyme arthritis (LA), 1–2% 
may show Lyme nephritis (LN).
• Reported in humans, dogs, horses, and, 
sporadically, in cats.
• Experimentally, 2–5 months incubation 
period.
• LA—self-limiting episodic arthritis/
anorexia/fever due to interstitial migration of 
organisms and host immune responses.
• LN—associated with glomerular deposition 
of Bb-specific antigen–antibody complexes.
• In dogs, cardiac involvement rare.
• Organisms persist associated with collagen and 
fibroblasts in skin, joints, tendons, pericardium, 
peritoneum, meninges, muscle, heart, and 
lymph nodes; rarely found in body fluids.
• Pathologic changes—with few exceptions 
restricted to joints, draining lymph nodes; rarely, 
immune-complex glomerulonephritis (ICGN).
GENETICS
Genetic predisposition for infection (not 
illness) in beagles and Bernese mountain dogs. 
Labrador and golden retrievers are predisposed 
to LN, but it remains rare (proteinuria is not 
associated with seropositivity).
• Seroprevalence in dogs varies with exposure 
to infected ticks in endemic areas (5–30%). In 
some areas before tick control was common, 
seroprevalence was 70–90% in healthy dogs.
• Clinical Lyme borreliosis (LB) develops in 
small fraction of infected individuals; 
coinfections with other organisms (e.g., 
Anaplasma phagocytophilum ) may impact 
outcome.
• Northern hemisphere:
 ◦North America—most cases reported in 
the Mid-Atlantic states, New England, 
Upper Midwest, adjacent Canada. Ecologic 
conditions supporting LB exist in adjacent 
states and on West Coast.
 ◦Europe—central; less frequent in areas 
bordering Mediterranean basin.
Species
Dog and rarely cat.Mean Age and Range
Experimentally, puppies are more susceptible 
than adult dogs.
SIGNS
• LA—acute or recurrent lameness in one or 
more legs; possible fever, anorexia, depression, 
local lymphadenopathy. Affected joints may 
be swollen, warm, painful. Self-limiting or 
responds well to antibiotic treatment.
• Experimentally—puppies developed acute 
self-limiting (3–4 days) form of LA in the leg 
closest to tick bite; may reoccur weeks later in 
the same or other leg. Older puppies had 
fewer signs; adult untreated dogs showed no 
clinical signs but had histologic changes of 
chronic nonerosive polyarthritis; 10–15% 
were persistent carriers despite antimicrobial 
therapy
• LN—protein-losing nephropathy (PLN) 
due to ICGN; may present for renal failure, 
thromboembolism, hypertension, or 
nephrotic syndrome.
CAUSES
• Bb—transmitted by three-host Ixodes  ticks.
• Infection—usually after nymph or adult 
female tick attachment for 2–4 days.
Ixodes Ticks
• 2- to 3-year life cycle depending on 
availability of hosts.
• Summer—uninfected eggs laid, hatch in 
several weeks; become infected by feeding on 
infected host (small mammal or bird).
• Following spring—larvae molt into nymphs;  
stay or become infected by feeding on 
infected host.
• Fall—nymphs molt into adults which stay 
infected; females mate, feed on larger 
mammals (e.g., deer); drop off and hide 
under leaves until laying eggs following 
summer; males rarely attach or feed.
Canine LB is a peridomestic disease due to 
expansion of housing into tick habitat; outdoor 
activities in endemic areas put dogs at risk.
  DIAGNOSIS
Diagnosis based on clinicopathologic signs, 
response to antibiotic therapy, exclusion of 
other diagnoses, serologic evidence of natural 
exposure antibodies, and history of exposure 
to ticks in endemic or emerging area.
• LA—infectious (anaplasmosis, ehrlichiosis, 
Rocky Mountain spotted fever), inflammatory 
(immune-mediated polyarthropathy, lupus, 
rheumatoid arthritis), and genetic (Akita, 
shar-pei) arthritides; degenerative joint disease; neuromuscular, traumatic, or other 
causes of lameness or weakness.
• LN—leptospirosis, ICGN caused by 
babesiosis, dirofilariasis, leishmaniasis, lupus, 
neoplasia; amyloidosis, glomerulosclerosis, 
genetic, toxic, and other causes of glomerular 
disease.
• LA—unremarkable.
• LN—proteinuria, hypoalbuminemia, 
hypercholesterolemia; later azotemia, 
hyperphosphatemia, thrombocytopenia, 
isosthenuria, glucosuria.
• Joint tap cytology—hypercellular (up to 
75,000 neutrophils/ μL).
• Antibodies—VlsE, C6, and OspF 
antibodies; OspA and OspC antibodies may 
be induced by vaccines or natural exposure.
• ELISA to detect a subgroup of antibodies 
against outer surface protein VlsE of Bb 
using C6 peptide; C6 antibodies wane 3–6 
months after antibiotic therapy. Low to 
moderate pretherapy C6 levels do not drop 
significantly.
IMAGING
• Thoracic radiographs, abdominal ultrasound—  
rule out other causes of proteinuria. Usually 
no ultrasonographic renal changes in LN 
dogs.
• Orthopedic radiographs—joint effusion, 
distinguish erosive from nonerosive joint 
disease; rule out trauma.
• Experimentally, organisms may be 
demonstrated in skin (tick bite site) or synovium 
with PCR or culture; these tests are time-
consuming, unreliable, and not recommended.
• Blood samples typically test negative via 
PCR or culture.
Gross
• Swollen joints with joint effusion.
• Possible local lymphadenopathy.
• PLN: may include peripheral edema, 
effusions, thromboembolism, hypertensive 
organ damage (retinal hemorrhage/
detachment, left ventricular hypertrophy, 
cerebrovascular disease).
• LA—acute arthritis, fibrinopurulent 
synovitis. Mild lymphoplasmacytic synovitis 
in other joints.
• Lymph nodes—possible cortical 
hyperplasia, multiple enlarged follicles, 
expanded parafollicular areas.
• Superficial dermis near tick bite site—
perivascular lymphoplasmacytic infiltrate 
with some mast cells.Lyme Borreliosis

848  Blackwell’s Five-Minute Veterinary Consult  
L• LN—ICGN, diffuse tubular necrosis with 
regeneration, interstitial inflammation.
  TREATMENT
LA—outpatient; LN—may require hospitaliza -
tion, IV fluids, colloids, and PLN therapy, 
antiemetics, etc.
Consider leptospirosis differential (isolation) 
for LN suspects.
DIET
LA—no change needed; LN—renal diets, 
omega-3 fatty acid supplement.
• Antibiotics should be administered as 
prescribed.
• Discuss the risk to humans in same environs.
• Aspiration of synovial fluid—may be 
considered for diagnostic purposes.
• Renal biopsy may be indicated to 
differentiate ICGN from other causes of renal 
• Antibiotics: may not clear infection 
completely; treatment significantly improves 
LA clinical signs and pathology:
 ◦Doxycycline 5–10 mg/kg PO q12h, with 
food; preferred.
 ◦Amoxicillin 20 mg/kg PO q8–12h.
 ◦Azithromycin 25 mg/kg PO q24h.
• Recommended treatment period—4 weeks 
for LA; LN may be treated until Quant C6 
level wanes.
• Additional therapy for PLN/ICGN may 
include renin–angiotensin–aldosterone system 
inhibitors, antithrombotics, antihypertensives, etc. 
(see consensus statement in Suggested Reading).
• Immunosuppressive drugs (e.g., mycophe-
nolate, corticosteroids) indicated if biopsy-
confirmed ICGN or rapid deterioration 
despite standard treatments.
Consider potential drug side effects. Renal 
biopsy contraindicated in dogs with severe 
thrombocytopenia, unregulated hypertension, 
or end-stage renal failure.
Doxycycline can be used during growth 
without fear of dental harm; may cause 
esophagitis or gastritis.ALTERNATIVE DRUG(S)
Nonsteroidal medications—not recommended 
initially; use caution with renal dysfunction or 
prior corticosteroid therapy.
  FOLLOW-UP
• Improvement—in acute LA seen within 
1–3 days of antibiotic treatment.
• If no improvement or if signs exacerbate—
consider other diagnoses.
• All seropositive dogs should be screened, 
monitored, and treated if proteinuria present.
• Mechanical removal of ticks.
• Prevention of tick attachment or fast 
kill—acaricides and repellents supplied as 
topicals, collars, or oral medications.
• Vaccines—5 currently available 
(nonadjuvanted recombinant OspA, 
3 adjuvanted bacterins, and an adjuvanted 
recombinant chimeric OspA with 7 strains of 
OspC). All induce antibodies against spirochete’s 
OspA to kill the spirochete within the tick while 
it feeds. Bacterins (produced from inactivated 
cultured Bb organisms) and the recombinant 
chimeric OspA/OspC also induce OspC 
antibodies to kill spirochetes within the host.
 ◦Efficacy is improved by booster 
immunizations at 6 months after an initial series; 
at least annual booster is needed thereafter.
 ◦Tick control still recommended because 
of inconsistent vaccinal efficacy and 
duration of immunity.
• Year-round tick population control in 
environment—restricted to small areas; clear 
leaf piles, difficult to reduce host mammal 
Renal failure.
• Recovery from acute lameness expected 
1–3 days after starting antibiotics.
• Recurrence of LA signs may be due to 
coinfection or reinfection, not necessarily relapse.
• Prognosis for LN is largely unknown but 
appears to vary as for other PLN/ICGN cases.
• Infection in humans acquired only from 
infected ticks.
• Dogs can transport unattached ticks which 
can later attach to humans—however, ixodid 
ticks are not intermittent feeders; once 
feeding starts, they do not change hosts. PREGNANCY/FERTILITY/
BREEDING
• No convincing evidence that Bb infection is 
transmitted in utero  in dogs.
• Avoid tetracyclines in pregnant animals.
• Maternal C6 antibodies can be passed to 
puppies.
SYNONYMS
Lyme arthritis, Lyme nephritis, or Lyme 
disease.
• Bb = Borrelia burgdorferi .
• ICGN = immune-complex 
• LA = Lyme arthritis.
• LB = Lyme borreliosis.
• LN = Lyme nephritis.
• PLN = protein-losing nephropathy.
• Centers for Disease Control and 
Prevention: http://www.cdc.gov/lyme
• Companion Animal Parasite Council: www.
capcvet.org
• IRIS Glomerular Disease Study Group: 
https://onlinelibrary.wiley.com/
toc/19391676/27/s1
Borys MA, Kass PH, Mohr FC, et al. 
Differences in clinicopathologic variables 
between Borrelia  C6 antigen seroreactive 
and Borrelia  C6 seronegative 
glomerulopathy in dogs. J Vet Intern Med 
2019, 33:2096–2104.
Greene CE, Straubinger RK, Levy SA. 
Borreliosis. In: Greene CE, ed., Infectious 
Diseases of the Dog and Cat, 4th ed. 
St. Louis, MO: Saunders Elsevier, 2012, 
pp. 447–465.
IRIS Canine GN Study Group Standard 
Therapy Subgroup, Brown S, Elliott J, et al. 
Consensus recommendations for standard 
therapy of glomerular disease in dogs. J Vet 
Intern Med 2013, 27(S1):S27–S43.
Littman MP , Gerber B, Goldstein RE, et al. 
ACVIM consensus update on Lyme 
borreliosis in dogs and cats. J Vet Intern 
Med 2018, 32:887–903.
Author  Meryl P . Littman
Reinhard K. Straubinger.
available onlineLyme Borreliosis  (continued)

Canine and Feline, Seventh Edition  849
L  BASICS
An obstructive disorder of the lymphatic 
system of the gastrointestinal (GI) tract, 
resulting in lymphatic hypertension and 
protein-losing enteropathy (PLE).
• Lymphatic obstruction results in dilation 
and rupture of intestinal lacteals with 
subsequent loss of lymphatic contents 
(plasma proteins, lymphocytes, and 
chylomicrons) into the intestinal lumen.
• Although some of the proteins may be 
digested and reabsorbed, excessive enteric loss 
of plasma proteins will ultimately result in 
panhypoproteinemia.
• Hypoproteinemia causes a decrease in plasma 
oncotic pressure, which, if severe, will lead to 
ascites, pleural effusion, and/or (rarely) edema.
• Loss of antithrombin and other anticoagu -
lants can cause a hypercoaguable state.
• GI—diarrhea.
• Respiratory—pleural effusion.
• Skin—subcutaneous edema.
• Systemic—ascites.
• Vascular—thromboembolic disease.
GENETICS
A familial tendency for PLE has been 
reported for soft-coated wheaten terriers, 
basenjis, Yorkshire terriers, and Norwegian 
lundehunds, but the actual genetic cause has 
not been identified for any of these breeds.
Uncommon
N/A
Species
Dog
Soft-coated wheaten terrier, basenji, 
Norwegian lundehund, Yorkshire terrier.
Any age; most common in middle-aged dogs.
Increased prevalence reported in female 
soft-coated wheaten terriers; no sex 
predilection reported for other breeds.
SIGNS
• Clinical signs are variable.
• Diarrhea—chronic; typically small bowel 
diarrhea; however, not all animals have diarrhea.
• Ascites.
• Subcutaneous edema.• Dyspnea from pleural effusion.
• Weight loss and sarcopenia.
• Flatulence.
CAUSES
Primary or Congenital Lymphangiectasia
• Focal—intestinal only.
• Diffuse lymphatic abnormalities (e.g., 
chylothorax, lymphedema, chyloabdomen, 
thoracic duct obstruction).
Secondary Lymphangiectasia
• Constrictive pericarditis.
• Budd–Chiari syndrome.
• Neoplasia (e.g., lymphoma, thymoma, 
mediastinal masses).
• Fungal disease.
N/A
  DIAGNOSIS
• Other causes of PLE.
• PLE must be differentiated from other 
causes of hypoalbuminemia.
• Panhypoproteinemia.
• Hypocholesterolemia.
• Lymphopenia.
Differentiate PLE from Other Causes 
of Hypoalbuminemia
• Serum chemistry and pre- and postprandial 
serum bile acids to rule out hepatic failure.
• Urine protein:creatinine ratio to rule out 
• Occult fecal blood test to rule out GI blood 
loss ( o-toluidine-based tests are preferable as 
these tests are less likely to be falsely positive 
due to meat in the diet than guaiac-based 
tests).
• Fecal α1-protease inhibitor to help confirm 
intestinal protein loss (most useful in dogs 
that do not yet have any GI signs).
Differentiate Other Causes of Excessive 
Protein Loss into the GI Tract
• Fecal smear and flotation to rule out 
intestinal parasites.
• Serum cobalamin and folate concentrations 
to rule out small intestinal dysbiosis or 
cobalamin deficiency. Cobalamin deficiency 
is an indicator of chronic severe distal small 
intestinal disease, which could be associated 
with excessive protein loss.• Fecal culture for diagnosis of specific enteric 
pathogens (e.g., Salmonella  spp.); PCR for 
enteropathogenic Campylobacter  spp. and 
other enteropathogens.
• Fluid analysis of cavitary effusions—
lymphangiectasia usually results in a 
transudate, but chyloabdomen and 
chylothorax may be observed.
• Chronic chylous effusions might be difficult 
to differentiate from modified transudates. 
In chylous effusions the triglyceride 
concentration is higher than in serum.
IMAGING
• Thoracic radiographs—survey to rule out 
cardiac disease and neoplasia.
• Abdominal radiographs—to rule out 
mechanical intestinal disease (obstruction or 
partial obstruction) and other causes of PLE. 
However, routine abdominal radiographs are 
less useful for assessment of these patients 
than abdominal ultrasound.
• Abdominal ultrasound—to rule out 
mechanical intestinal disease and other causes 
of PLE. Ultrasound often shows hyperechoic 
mucosal striations (“tiger stripe” effect), 
mucosal speckles, and/or a hyperechoic line 
within the mucosa running parallel to the 
submucosa. Corn oil 1–2 mL/kg given orally 
60–90 minutes before the study may improve 
the diagnostic yield.
• Echocardiography—to rule out right-sided 
congestive heart failure.
• Endoscopy—allows intestinal mucosal 
visualization and biopsy. Ileal biopsies should 
be procured in hypocobalaminemic animals.
• Laparotomy—allows visualization of dilated 
intestinal lymphatics and biopsies of intestines 
(full thickness) and lymph nodes, but may be 
contraindicated in patients with hypopro-
teinemia due to increased complications (e.g., 
dehiscence).
• ECG and/or echocardiography—can aid in 
evaluating animals suspected of having 
right-sided congestive heart failure or 
• Dilated lymphatics may appear as a 
web-like network throughout the mesentery 
and serosal surface.
• Lipogranulomas may appear as yellow-
white nodules and foamy granular deposits 
adjacent to lymphatics.
• Lacteal dilatation, villous blunting, and crypt 
lesions (i.e., dilatation, cysts, abscesses) are the 
most consistent findings on histopathology 
with lymphangiectasia and PLE.
• Often associated with mucosal edema or 
diffuse or multifocal accumulations of 
lymphocytes and plasma cells in the lamina 
propria.Lymphangiectasia

850  Blackwell’s Five-Minute Veterinary Consult  
L  TREATMENT
May need hospitalization if complications 
due to hypoalbuminemia develop.
Consider placement of an esophageal feeding 
tube in anorectic patients to meet increased 
caloric demands.
ACTIVITY
Normal
DIET
• Low-fat or ultra-low fat diets are the 
cornerstone of treatment.
• Commercial low fat diets contain 20 g 
fat/1000 kcal or less. A lower fat content with a 
novel protein source (if desired) can be 
achieved by a home-cooked diet. Protein 
sources may include chicken breast, tilapia, 
tuna, and/or fat-free cottage cheese. Possible 
carbohydrate sources are potato, rice, pasta, 
and/or egg noodles.
• Initially a simple home-cooked diet can be 
used, but long-term the diet must be balanced.
• Avoid high-fiber diets.
• Dogs with concurrent lymphangiectasia 
and inflammatory bowel disease may benefit 
from a commercial hydrolyzed protein diet 
that is moderately fat restricted.
• Long-chain triglycerides stimulate intestinal 
lymph flow and may lead to increased 
intestinal protein loss.
• Diets fortified with medium-chain 
triglycerides (MCTs) may be beneficial.
• May feed MCTs (e.g., MCT oil, Enfamil 
Portagen) to supplement fat and calorie intake.
• Supplement with fat-soluble vitamins— 
A, D, E, and K.
• Elemental diets can also be used.
Discuss unpredictable disease progression and 
• Patients that benefit from surgical 
intervention are rare.
• Consider surgery to relieve an identifiable 
lymphatic obstruction, if present.
• Pericardiectomy may be indicated with 
constrictive pericarditis.
• Clopidogrel 1–3 mg/kg PO q24h or 
ultra-low dose aspirin 0.5 mg/kg PO q24h to 
reduce the risk of thromboembolic events.• T ry corticosteroids if dietary therapy alone is 
unsuccessful (however, such therapy is not 
intended to treat lymphangiectasia but rather 
concurrent GI inflammation). Prednisone or 
prednisolone 1–2 mg/kg PO q12h for 5–7 
days, followed by 1 mg/kg q12h for at least 
6 weeks. In large-breed dogs the starting dose 
should be more conservative than in small-
breed dogs. After remission, dosage can be 
slowly tapered to the lowest dose effective at 
controlling the disease. Alternatively, consider 
the use of a locally effective corticosteroid (e.g., 
budesonide), or other immunomodulators such 
as chlorambucil, azathioprine, or cyclosporine.
• In hypocobalaminemic patients, cobalamin 
must be supplemented parenterally or orally 
to achieve therapeutic response (see 
Cobalamin Deficiency for dosing).
• If secondary small intestinal dysbiosis is 
suspected, the patient should be treated with 
tylosin at 20 mg/kg q12h for 6 weeks.
• Magnesium sulfate should be supplemented 
parenterally (IV) at 1 mEq/kg/day in dogs 
that are hypomagnesemic before oral 
supplementation with magnesium oxide, 
magnesium citrate, or magnesium carbonate.
• Diuretics such as furosemide 1 mg/kg q12h 
or spironolactone 1 mg/kg q12h in animals 
with severe ascites to improve comfort.
N/A
Steroids might increase the risk for 
Clopidogrel should not be used with 
phenytoin, torsemide, or warfarin.
Some patients may respond to treatment with 
octreotide; dosing for this condition is 
empirical.
  FOLLOW-UP
• Body weight, serum total protein, albumin, 
and globulin concentrations, and clinical 
signs (pleural effusion, ascites, and/or edema).
• Patients need to be reevaluated depending 
on the severity of the disease process.
N/A
• Dyspnea from pleural effusion or 
pulmonary thromboembolism.• Severe protein-calorie depletion.
• Intractable diarrhea.
• Prognosis is guarded. More than 50% of 
patients die from the disease or from 
associated thromboembolic disease.
• Remissions of several months to more 
than 2 years can be achieved in some  
patients.
Soft-coated wheaten terriers may have 
concurrent protein-losing nephropathy.
SEE ALSO
• GI = gastrointestinal.
• MCT = medium-chain triglycerides.
• PLE = protein-losing enteropathy.
Kull PA, Hess RS, Craig LE, et al. Clinical, 
clinicopathologic, radiographic, and 
ultrasonographic characteristics of intestinal 
lymphangiectasia in dogs: 17 cases 
(1996–1998). J Am Vet Med Assoc 2001, 
219:197–202.
Larson RN, Ginn JA, Bell CM, et al. 
Duodenal endoscopic findings and 
histopathologic confirmation of intestinal 
lymphangiectasia in dogs. J Vet Intern Med 
2012, 26:1087–1092.
Littman MP , Dambach DM, Vaden SL, et al. 
Familial protein-losing enteropathy and 
protein-losing nephropathy in soft coated 
wheaten terriers: 222 cases (1983–1997). 
J Vet Intern Med 2000, 14:68–80.
Okanishi H, Yoshioka R, Kagawa Y, et al. The 
clinical efficacy of dietary fat restriction in 
treatment of dogs with intestinal 
lymphangiectasia. J Vet Intern Med 2014, 
28:809–817.
Pollard RE, Johnson EG, Pesavento PA, et al. 
Effects of corn oil administered orally on 
conspicuity of ultrasonographic small 
intestinal lesions in dogs with 
lymphangiectasia. Vet Radiol Ultrasound 
2013, 54:390–397.
Authors  Jörg M. Steiner and Sina Marsilio
available onlineLymphangiectasia  (continued)

Canine and Feline, Seventh Edition  851
L BASICS
• Lymphadenopathy—lymph node 
• Generalized lymphadenopathy—enlarge-
ment of multiple lymph nodes.
• Lymphoid hyperplasia/reactivity—benign, 
non-neoplastic, reactive response to immune 
stimulation; results in proliferation of plasma 
cells and lymphocytes of all sizes, which 
results in lymphadenopathy.
• Lymphadenitis—inflammation of the 
lymph node; can represent primary infection 
of the lymph node or drainage of regional 
• Lymphoid hyperplasia/reactivity—can 
occur secondary to a localized process like 
dental disease or localized skin allergies (i.e., 
pododermatitis). Lymphoid hyperplasia can 
also be seen secondary to systemic inflamma-
tion. Lymph node enlargement can be 
singular or generalized.
• Lymphadenitis—inflammation within a 
lymph node can represent a primary process 
(inflammation or necrosis of the lymph node 
itself) or a secondary process (drainage of an 
area of inflammation or necrosis).
• Infectious lymphadenitis—the drainage 
function of lymph nodes increases their 
exposure to infectious agents within the node.
• Noninfectious lymphadenitis—often occurs 
secondary to drainage of areas of inflammation.
• Neoplasia—primary lymph node neoplasia 
(lymphoma) or metastatic disease. Lymph node 
enlargement can be singular or generalized.
• May be a component of more widespread 
GENETICS
No known genetic basis for lymphoid 
hyperplasia/reactivity or lymphadenitis.
• Seen with a variety of systemic diseases.
• Overall incidence is unknown.
Geographic distribution should be considered 
in cases of lymphadenitis caused by fungal 
Species
None for lymphoid hyperplasia or lymphad-
enitis. Increased incidence of lymphoma can be seen in golden retrievers, basset hounds, 
St. Bernard, boxer, Scottish terrier, Airedale 
terrier, Rottweiler, Labrador retriever, bull 
mastiff, and bouvier des Flandres.
None
None
SIGNS
• Marked submandibular lymph node 
enlargement can result in difficulty swallowing.
• Clinical signs are often related to systemic 
disease.
• Owners may report finding mass lesions, 
particularly when lymph node enlargement is 
marked.
• Systemic signs of inflammatory disease or 
organ dysfunction may be reported.
• Hyperplastic lymph nodes vary in size. In 
early stages, lymph nodes may be firm yet still 
mobile.
• Inflamed lymph nodes are typically large 
and firm and may be painful.
• Bacterial infection can result in abscess 
formation within the node, which may 
rupture and result in draining tracts. Patients 
may also have fever and other systemic signs 
• Lymph nodes affected by lymphoma are 
often at least twice normal size and very firm.
• Lymph nodes with metastatic neoplasia can 
have a variable presentation.
CAUSES
Lymphoid Hyperplasia/Reactivity
• Hyperplastic lymph nodes represent a 
proliferation of lymphocytes in response to 
any source of antigenic stimulation.
• Stimulation can be localized where a lymph 
node drains an area of inflammation.
• Systemic disease can also result in hyper-
plastic/reactive lymph nodes.
• Chronic hyperplasia can occasionally lead 
to lymphadenitis.
• A benign condition has been reported in 
young cats, featuring generalized lymphad-
enopathy characterized by increased numbers 
of intermediate to large lymphocytes, which 
can mimic lymphoma. Care must be taken 
not to misdiagnose these patients with 
lymphoma.
• Generalized lymphadenopathy can occur in 
cats infected with Bartonella  spp. or feline 
immunodeficiency virus (FIV).
Neutrophilic Lymphadenitis
• Commonly seen in lymph nodes draining a 
site of infection.• Bacterial infection will also result in 
neutrophilic lymphadenitis, including 
Streptococcus  spp., Brucella  spp., Francisella 
tularensis  (tularemia), and Yersinia pestis  
(bubonic plague). The latter two organisms 
are more likely to cause lymphadenitis in 
feline patients.
Eosinophilic Lymphadenitis
• Common with dermatitis and parasitic skin 
diseases.
• Can also be observed with drainage of mast 
cell tumors, some lymphomas, and with 
hypereosinophilic syndrome.
Granulomatous/Pyogranulomatous 
Lymphadenitis
• Indicative of chronic inflammation; can 
occur concurrently with neutrophilic 
lymphadenitis.
• Multinucleated giant cells with neutrophils 
indicate pyogranulomatous inflammation.
• Fungal, protozoal, and bacterial infections.
Neoplasia
• Lymphoma often results in generalized 
lymphadenopathy with marked lymph node 
• Metastatic neoplasia may cause a singular or 
generalized lymphadenopathy of variable size.
• Patients with compromised immune 
function due to chronic illness or immuno-
suppressive therapy can be more susceptible 
to infection and lymphadenitis.
infection may also be associated with 
lymphoid neoplasia.
 DIAGNOSIS
• It is essential to determine that a mass effect 
in the region of a lymph node is not a 
neoplastic mass or other regional structure 
(e.g., salivary gland).
• Differentiation between lymphoid 
hyperplasia, lymphadenitis, lymphoma, or 
metastatic neoplasia cannot be achieved by 
evaluating clinical signs alone.
• Fever and painful, enlarged lymph nodes 
are suggestive of lymphadenitis.
• Lymphoma and lymphoid hyperplasia are 
more common causes of generalized 
lymphadenopathy than lymphadenitis.
• Localized lymphoid hyperplasia secondary 
to local inflammation may not be associated 
with specific CBC/chemistry abnormalities.
• Patients with infectious causes of lymphad-
enitis may have marked hyperglobulinemia.Lymphadenopathy/Lymphadenitis

852  Blackwell’s Five-Minute Veterinary Consult  
L• Marked eosinophilia can be seen with 
hypereosinophilic syndrome or as a paraneo-
plastic phenomenon.
• Biochemistry results may reflect organ 
involvement from underlying disease 
process.
• Hypercalcemia can be seen in dogs with 
lymphoma, but this finding is uncommon in 
cats.
Serologic or urine antigen tests for various 
systemic fungal diseases are available.
IMAGING
• Radiographs—evaluate for enlargement of 
internal organs or patterns associated with 
• Ultrasound—evaluate intra-abdominal 
lymph nodes and organ architecture.
• Fine-needle aspiration cytology stained 
with a Romanowsky stain (e.g., Diff-Quik) 
in most cases is sufficient for diagnosis of the 
primary cause of lymph node enlargement.
• Culture of aspirated material or a fresh 
tissue sample obtained via tissue biopsy can 
be considered if an infectious etiology is 
• Fine-needle aspiration/cytology results:
◦ Lymphoid hyperplasia—increased 
numbers of intermediate and large 
lymphocytes (<50% of the total popula-
tion); increased numbers of plasma cells.
◦ Lymphadenitis—increased numbers of 
neutrophils, eosinophils, macrophages, or 
a combination of these types.
◦ Infectious agents—bacterial, fungal, and 
protozoal organisms can be found free in 
the background or within the cytoplasm of 
macrophages and, rarely, neutrophils.
◦ Lymphoma—over 50% of the lympho-
cyte population is made up of immature 
lymphocytes. Immature cells can be 
intermediate to large in size. Some forms of lymphoma (e.g., indolent lymphoma) 
cannot be diagnosed with cytology alone 
and may require advanced diagnostics 
including flow cytometry or PCR for 
antigen receptor rearrangement (PARR).
◦ Metastatic neoplasia—findings include 
the presence of cells not normally observed 
in a lymph node and can range from rare 
nests of neoplastic cells to complete 
effacement of the lymph node.
• When a definitive diagnosis cannot be 
made with cytology alone, a lymph node 
biopsy may be required, particularly if 
cytology results are consistently inconclusive 
or if enlargement of a lymph node is 
persistent, progressive, or unexplained.
 TREATMENT
T reatments are aimed at the underlying 
etiology.
• Effective drug therapy involves identifica-
tion and treatment of the underlying cause.
• Solitary enlarged lymph nodes with 
neutrophilic lymphadenitis are likely to have 
a bacterial component either within the node 
or the primary drainage area.
• Chemotherapeutic agents can be used to 
treat lymphoma.
 FOLLOW-UP
Variable MISCELLANEOUS
None
• Bubonic plague, tularemia, and mycobacte-
rial infections may present risk of human 
• Specimens from affected animals should be 
handled with appropriate caution.
Cowell R, Dorsey K, Meinkoth J. Lymph 
node cytology. Vet Clin Small Anim 2003, 
33:47–67.
Messick JB. The lymph nodes. In: Valenciano 
AC, Cowell RL, eds., Cowell and Tyler’s 
Elsevier, 2014, pp. 180–194.
Raskin RE. Hemolymphatic System. In: 
Raskin RE, Meyer DJ, eds., Canine and 
Feline Cytology, 3rd ed. St. Louis, MO: 
Saunders, 2016, pp. 91–117.
Viall VEO, Kiupel M, Bienzle D. 
Hematopoietic system: lymph nodes. In: 
Maxie, G, ed., Pathology of Domestic 
Animals, 6th ed. Vol. 3. St. Louis, MO: 
Elsevier, 2016, pp. 196–215.
Author  Corry K. Yeuroukis
Kenneth M. Rassnick and Alan H. Rebar.Lymphadenopathy/Lymphadenitis  (continued)

Canine and Feline, Seventh Edition  853
L BASICS
OVERVIEW
• Pathologic accumulation of protein-rich 
lymph into interstitial spaces, especially 
subcutaneous fat due to primary/secondary 
failure of lymphatic drainage. • If chronic, 
causes tissue fibrosis. • May be congenital or 
acquired.
• Dog (more common) and cat. • Congenital 
in bulldogs. • Hereditary/congenital in a 
family of poodles and whippets. • Possible 
breed predilection in Labrador retrievers and 
Old English sheepdogs.
SIGNS
• Primary/congenital—peripheral limb 
swelling/pitting edema at birth or develops 
within the first several months. • Progressive, 
nonpainful swelling starting at distal extremity 
and slowly advances proximally.
• Most common in limbs, especially pelvic 
limbs; unilateral or bilateral. • Less common 
in ventral thorax, abdomen, ears, and tail. 
• Nonpainful pitting; affected area is 
normothermic. • Pitting quality lost with 
chronicity as fibrosis occurs. • Lameness and 
pain uncommon unless cellulitis develops.
• Hereditary/congenital malformation of 
lymphatics—aplasia of thoracic duct, cisterna 
chyli or peripheral lymphatics, valvular 
incompetence, and lymph node fibrosis. 
• Excessive interstitial fluid production due 
to venous hypertension (e.g., congestive heart 
failure, venous obstruction) or increased 
vascular permeability (e.g., infection, trauma, 
heat, irradiation). • Secondary damage to 
lymphatic vessels or lymph nodes—associated 
with trauma, infection (e.g., Brugia pahangi  
lymphatic filarial infection—Southeast Asia), 
neoplasia (e.g., lymphoma, lymphangiosarcoma 
[rare]), radiation therapy and thoracic duct 
ligation (rare).
  DIAGNOSIS
• Edema due to venous stasis (e.g., congestive 
heart failure, cirrhosis); look for varices, 
hyperpigmentation, and ulceration. 
• Arteriovenous fistulae—listen for machin-
ery murmur; feel for pulsatile vessels; confirm 
with angiogram. • Edema due to hypopro-
teinemia—protein-losing nephropathy or 
enteropathy, hepatic failure, serum loss from 
burns or hemorrhage; check serum protein concentration. • T rauma—review history; 
look for bruising and lacerations. 
• Neoplasia—if swelling is firm, obtain 
aspirate for cytology. • Cellulitis—fever, pain, 
and warm swelling. • Insect bites.
Normal
Serologic tests for tick-borne infections, 
including Bartonella  spp.
IMAGING
• Radiography and ultrasound to rule out 
obvious masses. • Lymphangiography ± 
computed tomography allows evaluation of 
lymphatic abnormalities; best results obtained 
with direct injection of water-based contrast 
media into a lymphatic vessel (see Suggested 
Reading).
• Biopsy of affected tissues to rule out 
lymphangiosarcoma. • Culture and sensitivity 
when lymphangitis present.
  TREATMENT
• No curative therapy—a number of surgical 
and medical treatments may be tried. • Rest 
and massage of the affected limbs do not help. 
• Conservative care—long-term use of 
pressure wraps, coupled with skin care and use 
of antibiotics to treat cellulitis and lymphangi -
tis; may be successful in some patients. 
• Surgical procedures—attempted when 
conservative care and medications fail; two 
main categories: (1) Facilitate lymph drainage 
(lymphangioplasty, bridging techniques, 
lymphaticovenous shunts, superficial and deep 
lymphatic anastomosis). (2) Excisional 
procedures to remove abnormal tissue; no 
treatment consistently beneficial; excisional 
procedures reported in dogs only. • In 
humans—microwave heating of affected areas 
appears beneficial and adds to the effect of 
benzopyrones (see Drugs of Choice). • Diets 
severely restricted in long-chain triglycerides 
are being investigated in humans.
• Benzopyrones reduce high-protein edema 
by stimulating macrophages to release 
proteases with resulting fragmented proteins 
reabsorbed into the blood; beneficial effects 
have been recorded in experimental studies in 
dogs (e.g., rutin 50 mg/kg PO q8h). A study 
in humans showed combined usage of oral 
and topical benzopyrones to be more effective 
than either alone. • Diuretics, steroids, 
anticoagulants, and fibrinolytic agents have been used, but no confirmed benefit. • T reat 
underlying cause where possible (e.g., 
ivermectin for Brugia pahangi  infection).
Diuretics—initially reduce swelling but 
increase protein content of interstitial fluid, 
resulting in further tissue damage and 
fibrosis.
  FOLLOW-UP
• Puppies with severe lymphedema may die. 
• Spontaneous resolution may be seen in 
some puppies with pelvic limb involvement. 
• Prognosis with lymphangiosarcoma is poor.
Fossum TW, King LA, Miller MW, et al. 
Lymphedema: clinical signs, diagnosis, and 
treatment. J Vet Intern Med 1992, 
6:312–319.
Fossum TW, Miller MW. Lymphedema: 
etiopathogenesis. J Vet Intern Med 1992, 
6:283–293.
Author  Stuart A. Walton
acknowledge the prior contribution of Francis 
W.K. Smith, Jr.Lymphedema

L
854  Blackwell’s Five-Minute Veterinary Consult  
L  BASICS
Malignant transformation of lymphocytes.
Viral (feline leukemia virus [FeLV]) or 
chemical (tobacco smoke) oncogenesis.
• Gastrointestinal. •  Hemic/lymphatic/
immune. •  Nervous—most common spinal 
cord tumor in cats. • Ophthalmic. •  Renal 
(high rate of relapse in CNS). 
• Respiratory—nasal, thoracic cavities.
GENETICS
N/A
• About 90% of hematopoietic tumors and 33% 
of all tumors in cats. •  Prevalence—41.6–200 
per 100,000 cats.
Regional differences may relate to differences 
in FeLV prevalence.
Siamese/Oriental breeds overrepresented in 
some studies.
• FeLV-positive cats—3 years. •  FeLV-
negative cats—7 years. •  Median age of cats 
with localized extranodal lymphoma—13 
years. •  Most cats with Hodgkin’s-like 
lymphoma are older than 6 years.
None
SIGNS
Depend on anatomic form.
• Mediastinal form—open-mouthed 
breathing, coughing, regurgitation, anorexia, 
weight loss. •  Alimentary form—anorexia, 
weight loss, lethargy, vomiting, constipation, 
diarrhea, melena, hematochezia. Small cell 
lymphoma (SCL) typically more chronic signs 
compared to large cell lymphoma (LCL). 
• Renal form—consistent with renal failure. 
• Nasal form—nasal discharge or epistaxis, 
facial swelling, ocular signs, respiratory noise, 
sneezing, anorexia. •  Multicentric form—  
possibly none except for swellings in areas of 
lymph nodes in early stages; anorexia, weight 
loss, and depression with progression of 
disease. •  Spinal form—quickly progressing 
posterior paresis may be seen. •  Cutaneous 
form—pruritic, hemorrhagic, or alopecic 
dermal masses may be seen.Physical Examination Findings
• Mediastinal form—non-compressible cranial 
thorax, dyspnea, tachypnea. •  Alimentary 
form—thickened intestines or abdominal 
masses. •  Renal form—large, irregular kidneys. 
• Nasal form—purulent or mucoid nasal 
discharge, facial deformity, epiphora, 
exophthalmos, poor globe retropulsion. 
• Multicentric form—generalized lymphad -
enomegaly, possible hepatosplenomegaly. •  All 
forms—fever; dehydration; depression; 
cachexia in some patients.
CAUSES
FeLV
• FeLV exposure. •  Exposure to environmen-
tal tobacco smoke (relative risk 2.4, increases 
linearly with duration and quantity of 
exposure). •  Feline immunodeficiency virus 
(FIV) infection.
  DIAGNOSIS
• Mediastinal form—congestive heart failure; 
cardiomyopathy; chylothorax; pyothorax; 
hemothorax; pneumothorax; diaphragmatic 
hernia; allergic lung disease; thymoma; 
ectopic thyroid carcinoma; pleural carcinoma -
tosis; acetaminophen toxicity. •  Alimentary 
form—foreign body ingestion; intestinal 
ulceration; intestinal fungal infection; 
inflammatory bowel disease; intussusception; 
lymphangiectasia; other gastrointestinal 
tumor. •  Renal form—pyelonephritis; 
amyloidosis; glomerulonephritis; chronic 
renal failure; polycystic kidneys; feline 
infectious peritonitis. •  Multicentric 
form—systemic mycotic infection; immune-
mediated disease; toxoplasmosis; lymphoid 
h yperplasia; hypersensitivity reaction; plague 
(specifically if prominent cervical lymphad-
enopathy as with Hodgkin’s-like form).
• May see anemia (negative prognostic 
factor), leukocytosis, and lymphoblastosis. 
• May find high creatinine, high serum 
urea nitrogen, high hepatic enzyme activity, 
hypercalcemia (rare), and monoclonal 
gammopathy.
FeLV testing—usually negative in older cats 
and in cats with large granular lymphocyte 
lymphoma (LGLL), usually positive in 
younger cats and those with mediastinal (85%) 
or CNS lymphoma, renal (45% positive), 
multicentric (20%), intestinal (15%).IMAGING
• Thoracic radiography—may see 
m ediastinal mass, pleural effusion, abnormal 
pulmonary parenchymal patterns (rare), 
perihilar or retrosternal lymphadenomegaly. 
• Abdominal ultrasonography—may see 
diffuse echotexture changes in the liver, 
spleen, and kidneys, focal or diffuse 
thickening of the intestines and the gastric 
wall, abdominal lymphadenopathy, 
intestinal/gastric mass: ◦ Hypoechoic 
subcapsular thickening is associated with 
renal lymphoma. ◦ Despite thickening of 
intestines, layering may be preserved.  
• Computed tomography—space-occupying 
mass effect in affected area, especially used 
for nasal lymphoma.
• Aspiration or biopsy of a mass or lymph 
node. •  Aspirate often sufficient to diagnose 
LCL; biopsy often required for SCL. •  Can 
be challenging to distinguish SCL from 
inflammatory bowel disease (IBD). 
• Immunohistochemistry (IHC) ± PCR for 
antigen receptor rearrangement (PARR) 
testing can be done to distinguish between 
IBD and SCL; sensitivity of IHC for 
detecting lymphoma 78% vs. 83% for 
IHC + PARR; sensitivity of PARR for 
detecting T-cell and B-cell lymphoma is 
78% and 50%, respectively. •  Staging—
CBC/chemistry profile/urinalysis/FeLV/FIV 
testing, thoracic radiographs, abdominal 
ultrasound, regional lymph node aspirates 
for localized lesions, ± bone marrow aspirate 
depending on CBC findings; serum 
cobalamin level in SCL.
• Gross—usually white to gray in color with 
areas of hemorrhage and necrosis.  
• Cytologic—monomorphic population of 
intermediate to large sized immature 
lymphocytes (lymphoblasts) in LCL vs 
monomorphic population of small mature 
lymphocytes in SCL. •  Histopathologic—
vary; several morphologic classification 
schemes in use: ◦ Nasal lymphoma is most 
often immunoblastic B-cell origin. ◦ 
Hodgkin’s-like lymphoma is characterized by 
Reed–Sternberg cells and few neoplastic cells 
in a background of a reactive T-cell popula-
tion with histiocytes and granulocytes. ◦ LGL 
lymphoma most commonly affects the 
intestine and mesenteric lymph nodes. ◦ 
B-cell most common in stomach (100%) and 
large intestine (88%); T-cell most common in 
small intestine (52%). ◦ In gastrointestinal 
(GI) lymphoma, LCL more common than 
SCL when both cytologic and histopathologic 
samples are evaluated.Lymphoma—Cats

Canine and Feline, Seventh Edition  855
LL  TREATMENT
Outpatient whenever possible, supportive 
care if needed.
Fluid therapy, antiemetics, appetite stimulants, 
analgesia, thoracocentesis, etc. when indicated.
ACTIVITY
Normal
DIET
No change, can add n-3 fatty acids to diet 
(fish oil origin).
• Emphasize that side effects are treatable and 
should be addressed promptly. •  Inform client 
that the goal is to induce remission and achieve 
a good quality of life for as long as possible.
• To relieve intestinal obstructions or perfora -
tions and remove solitary masses. •  To obtain 
specimens for histopathologic examination.
RADIATION THERAPY
Possible option for localized lesions, such as 
nasal cavity or mediastinum, as well as rescue 
treatment for GI LCL.
• Chemotherapy—there are many variations 
of similar combination protocols, all with 
similar efficacy. •  High-grade lymphoma can 
respond to CHOP-based protocols (cyclo-
phosphamide, doxorubicin, vincristine, 
prednisone/prednisolone) such as the 
University of Wisconsin–Madison protocol 
(alternating drugs in repeated sequence) or 
COP-based protocols (cyclophosphamide, 
vincristine, prednisone/prednisolone).  
• Vinblastine has similar efficacy but less GI 
toxicity compared to vincristine. •  SCL can 
respond to oral chlorambucil (either low dose 
daily/every other day or high dose pulsed) 
and prednisone/prednisolone. •  Consult a 
veterinary oncologist for doses, schedules, and 
to help assess best option(s) for treatment.
Avoid doxorubicin in cats with preexisting renal 
failure as high-cumulative dosages have been 
demonstrated to potentially be nephrotoxic.
• Myelosuppression secondary to chemo-
therapy—more in FeLV-positive cats. •  Seek 
advice before initiating treatment if you are unfamiliar with cytotoxic drugs. Some drugs 
such as vincristine and doxorubicin are 
vesicants and can cause severe tissue sloughing 
if leaked outside the vein.
  FOLLOW-UP
• Physical examination and CBC—before 
each chemotherapy treatment and 1 week 
after each new drug is administered, or if 
there are concerns about low cell counts. 
• Diagnostic imaging—as necessary 
depending on location to assess response to 
therapy.
Avoid exposure to or breeding FeLV-positive 
cats.
• Leukopenia/neutropenia. •  Sepsis. 
• Anorexia, vomiting, weight loss; may need 
imaging tests to distinguish between chemo -
therapy side effects and lymphoma progression.
• Depends on initial response to chemotherapy, 
anatomic type, FeLV status, and tumor burden. 
• Median survival according to treatment 
(overall 50–70% response rate): ◦ Prednisone 
alone—1.5–2 months. ◦ COP/CHOP-based 
chemotherapy—6–9 months. •  Doxorubicin-
based, lomustine, MOMP (mechlorethamine, 
vincristine, melphalan, prednisone), and 
DMAC (dexamethasone, melphalan, actinomy -
cin-D, cytarabine) rescue therapy reported for 
refractory lymphoma. •  Median survival 
according to FeLV status: ◦ Negative—7 
months (17.5 months if low tumor burden).  
◦ Positive—3.5 months (4 months if low tumor 
burden). •  Median survival according to 
anatomic location: ◦ Renal—FeLV-negative, 
11.5 months; FeLV-positive, 6.5 months.  
◦ Nasal—1.5–2.5 years with radiation and 
chemotherapy. •  Chemotherapy may not 
improve survival over radiation alone. •  Higher 
radiation doses ( >32 Gy) result in longer 
survival. •  Mediastinal—about 10% of patients 
live >2 years. •  Alimentary—8 months.  
• Peripheral multicentric—23.5 months. •  If 
localized (median remission time)—114 weeks. 
• Median survival according to histology 
(tumor grade or subtype): ◦ SCL of GI tract 
with or without additional visceral involve -
ment—95% overall response to chlorambucil 
and prednisone for median survival of 
approximately 2 years (longer in complete vs. 
partial remission). ◦ LGLL—~30% response for 
median survival 57 days. •  Cats with 
Hodgkin’s-like lymphoma can do well for 
extended periods of time, even without treatment (months to years). •  Weight loss 
during first month of treatment of LCL 
associated with shorter survival. •  Clinical 
response after 1 cycle of COP chemotherapy 
associated with longer survival.
• Hypoglycemia (rare). •  Monoclonal 
gammopathy (rare). •  Hypercalcemia 
(10–15%).
Young cats with lymphoma are generally 
FeLV-positive.
None
Do not use chemotherapy in pregnant 
animals.
SYNONYMS
• Lymphosarcoma. •  Malignant lymphoma.
• IBD = inflammatory bowel disease.
• IHC = immunohistochemistry. 
• LCL = large cell lymphoma.
• LGLL = large granular lymphocyte 
lymphoma.
• SCL = small cell lymphoma.
Kiupel M, Smedley RC, Pfent C, et al. 
Diagnostic algorithm to differentiate 
lymphoma from inflammation in feline 
small intestinal biopsy samples. Vet Pathol 
2011, 48(1):212–222.
Vail DM. Feline lymphoma and leukemia. In: 
Withrow SJ, Vail DM, Page RL, eds., 
Withrow and MacEwen’s Small Animal 
Saunders Elsevier, 2013, pp. 638–653.
Wilson HM. Feline alimentary lymphoma: 
demystifying the enigma. Top Companion 
Anim Med 2008, 23(4):177–184.
Author  Erika L. Krick
acknowledge the prior contribution of Kim 
A. Selting.
available online (continued)  Lymphoma—Cats

856  Blackwell’s Five-Minute Veterinary Consult  
LLymphoma—Dogs
  BASICS
• Clonal proliferation of B-, T-, or non-B-/
non-T-type (null cell) lymphoblasts found 
primarily in enlarged peripheral lymph nodes. 
• Cells can spread systemically to invade bone 
marrow, peripheral blood, CNS, and visceral 
organs.
• ~85% of cases are multicentric (involving 
more than one lymph node). • ~75% are 
B-cell in origin and ~25% are T-cell in origin. 
• B-cell lymphoma (LSA) includes mainly 
multicentric B-cell lymphoma (80% of cases) 
which is an aggressive disease similar to human 
diffuse, large B-cell lymphoma (DLBCL), and 
marginal zone lymphoma (MZL, 20% of 
cases). Follicular lymphoma (FL) is rare. 
• Multicentric T-cell LSA includes aggressive 
(peripheral T-cell LSA—not otherwise 
specified [PTCL-NOS]) and indolent (T-zone 
LSA [TZL]) subtypes. T-cell LSAs are most 
commonly associated with hypercalcemia. 
• Aggressive lymphomas respond to treatment 
quickly, but have shorter overall survivals.
• Lymphatic (~85%)—generalized peripheral 
lymphadenopathy with or without splenic, 
hepatic, peripheral blood, and/or bone marrow 
involvement. • Gastrointestinal (~5–7%)—
focal or diffuse infiltration of intestines, and 
associated lymph nodes. • Mediastinal 
(~5%)—proliferation of neoplastic lympho -
cytes in mediastinal lymph nodes, thymus, or 
both. • Skin—divided into cutaneous 
non-epitheliotropic B- and T-cell LSA and 
mycosis fungoides (epitheleiotropic T-cell 
LSA). • Hepatosplenic γδ T-cell LSA 
(rare)—liver/spleen sinusoidal infiltration of 
T-cells with eventual bone marrow infiltration. 
Erythrophagia commonly seen. • Intravascular 
LSA (rare)—typically T- or null cell prolifera -
tion in lumen or wall of blood vessel.
GENETICS
• Some chromosome copy number aberrations 
are shared between human and canine lympho -
mas. • Gene expression profiling can be used 
to separate distinct subtypes of human and 
canine lymphoma. • Canine DLBCL and 
MZL may be a continuum of the same disease.
• 20–107 LSA cases per 100,000 dogs. • LSA 
comprises up to 24% of all canine neoplasms 
and 83% of all canine hematopoietic 
• Boxer, basset hound, golden retriever, Saint 
Bernard, Scottish terrier, Airedale terrier, and 
bulldog—reported high-risk breeds. • Dachshund and Pomeranian—reported 
low-risk breeds. • Breed determines relative risk 
for B-cell or T-cell disease: ~85% of boxer LSAs 
are T-cell in origin (>50% are CD3+CD4+ in 
origin), while golden retrievers develop both 
B- and T-cell LSA in an ~50:50 ratio.
Median Age
Historically, 6–9 years.
SIGNS
History
• Multicentric—from no clinical signs to 
anorexia, lethargy, vomiting, diarrhea, weight 
loss, fever, polydipsia and polyuria secondary to 
hypercalcemia. • Gastrointestinal—  vomiting, 
diarrhea, anorexia, weight loss, malabsorption. 
• Mediastinal—respiratory distress, pleural 
effusion, coughing, difficulty swallowing, caval 
syndrome. • Skin: ◦ Cutaneous LSA—lesions 
usually generalized or multifocal: nodules, 
plaques, ulcers, focal alopecia and hypopig -
mentation. ◦ Mycosis fungoides—initial 
scaling, alopecia, pruritus progressing to 
thickened, ulcerated, exudative lesions. Later 
stages include proliferative plaques and nodules 
with progressive ulceration. Oral mucosa many 
times involved. • Extranodal—vary with the 
anatomic site: ocular—photophobia and 
conjunctivitis; CNS—neurologic deficits, paresis, 
paralysis, seizures; hepatosplenic—lethargy, 
inappetance, weakness, icterus.
• Multicentric—generalized, painless, 
enlarged peripheral lymph node(s) with or 
without hepatosplenomegaly. 
• Gastrointestinal—unremarkable to palpable 
thickened gut loops and/or abdominal mass, 
rectal mucosal irregularities, ascites. 
• Mediastinal—dyspnea; tachypnea; muffled 
heart sounds secondary to pleural effusion, 
pitting edema of head, neck, forelimbs. 
• Skin—raised plaques that may coalesce, 
patch lesions, and erythematous, exudative 
lesions. • Extranodal—ocular—anterior 
uveitis, retinal hemorrhages, and hyphema; 
CNS—dementia, seizures, and paralysis.
CAUSES
Suggested causes include heritable breed risks, 
chromosomal aberrations, increased 
telomerase activity, germline and somatic 
genetic mutations, epigenetic changes, 
retroviral infection, Epstein–Barr virus 
infection, and environmental factors.
  DIAGNOSIS
• Multicentric—disseminated infections, 
metastatic disease, immune-mediated 
disorders, other hematopoietic tumors. 
• Gastrointestinal—other GI tumors, foreign 
body, enteritis, GI ulceration, systemic mycosis. • Mediastinal—other tumors 
(thymoma, chemodectoma, ectopic thyroid), 
infectious disease. • Skin—infectious 
dermatitis, pyoderma, immune-mediated 
dermatitis, histiocytic or mast cell disease. 
• Extranodal—depends on affected site.
• Anemia of chronic disease, thrombocytopenia, 
lymphocytosis, lymphopenia, neutrophilia, 
monocytosis, circulating blasts, hypoproteinemia 
(GI). • Hypercalcemia, increased liver 
enzymes with hepatic involvement, increased 
creatinine or blood urea nitrogen with renal 
involvement. • Urinalysis usually normal.
• Immunohistochemistry (lymph node [LN] 
biopsy/resection)—to determine immuno -
phenotype. • Flow cytometry or PCR for 
antigen receptor rearrangements (PARR) (LN 
or affected organ fine-needle aspirates)—to 
determine immunophenotype.
IMAGING
• Thoracic radiography—sternal or tracheo -
bronchial lymphadenopathy, widened 
mediastinum, pulmonary densities, and pleural 
effusion. • Abdominal ultrasonography—
abdominal lymphadenopathy, hepatosplenic 
involvement, thickened bowel loops, other 
visceral organ involvement, ascites.
• Fine-needle aspirate cytology of enlarged 
lymph nodes or other affected organs—for 
cytopathologic confirmation. • LN biopsy or 
resection—for accurate histopathologic 
classification. • Bone marrow cytology—for 
accurate prognosis. • CSF analysis—if patient 
has neurologic signs. • ECG—identify 
arrhythmias before doxorubicin administration.
• Multicentric— effacement of LN 
parenchyma with large, neoplastic CD79a+ 
B-cells (high-grade DLBCL) or perifollicular 
proliferation of CD79a+ cells (MZL) or 
CD79a+ cell proliferation that maintains 
follicle architecture (FL). Effacement of LN 
parenchyma with large, neoplastic CD3+ 
T-cells (PTCL-NOS) or small, CD3+ cell 
proliferation between fading follicles (indolent 
TZL). • Gastrointestinal—infiltration of 
neoplastic lymphocytes throughout mucosa 
and submucosa, with occasional transmural 
infiltration. • Skin—CD79a+ B-cells 
infiltrating mucosa and submucosa, but 
sparing the epidermis (non-epitheliotrophic) 
LSA or CD3+ T-cells invading the epidermis: 
Pautrier’s microabscesses (mycosis fungoides). 
Hepatosplenic—sinusoidal infiltration of 
erythrophagocytic CD3+ T-cells.
Staging
• I—one enlarged LN. • II—regionally 
enlarged LNs. • III—generalized LN involve -
ment. • IV—visceral organ involvement.

Canine and Feline, Seventh Edition  857
L• V—blood or bone marrow involvement. 
• Substage a—not sick. • Substage b—sick.
  TREATMENT
• High-grade LSAs are exquisitely sensitive to 
both chemotherapy and radiation. • Systemic 
multiagent chemotherapy—therapy of choice. 
• Radiation therapy—for refractory lympha -
denopathy, large mediastinal masses, and 
solitary cutaneous areas. Half-body irradia-
tion has been included into some chemo-
therapy protocols. • Surgery—rarely used 
unless an acutely obstructive GI mass is 
identified or to remove a refractory lympha -
denopathy. • Autologous and allogeneic bone 
marrow transplantation (BMT)—after total 
body irradiation can be considered. • Fluid 
therapy—for advanced disease to treat 
clinically ill, azotemic, and/or dehydrated 
patients. Fluid therapy, steroids, ±calci-
tonin—to treat hypercalcemia. • Consider 
aggressive fluid therapy—to prevent tumor 
lysis syndrome when inducing dogs with a 
high tumor burden or dogs with peripheral 
blood lymphoblasts.
• Canine LSA is a treatable, but rarely curable 
disease. • Side effects of chemotherapy drugs 
include reversible GI tract and bone marrow 
toxicities. • Most dogs will not experience 
alopecia, but, dogs who need grooming will. 
• The vast majority of dogs receiving chemo -
therapy enjoy an excellent quality of life.
• Consider combination chemotherapy 
protocols to treat intermediate and high-grade 
diseases and single-agent protocols to treat 
indolent diseases. • Most multiagent protocols 
have superior remission and survival times 
when compared to single-agent protocols. 
• Corticosteroids alone can induce significant 
multidrug resistance.
Intermediate and High-Grade 
Lymphomas
• L-CHOP— l-asparaginase 10,000 IU/m2, 
vincristine (Onvcovin) 0.7 mg/m2 IV,  
cyclophosphamide (Cytoxan) 250 mg/m2 IV or 
PO, doxorubicin (Adriamycin) 30 mg/m2 IV,  
prednisone 30, 20, 10 mg/m2 PO q24h 
tapering for 3 weeks. Consult a veterinary 
oncologist concerning the treatment schedule. 
• COP—vincristine 0.7 mg/m2 IV, cyclophos -
phamide (Cytoxan) 250 mg/m2 IV or PO, 
tapering for 3 weeks. Each drug given weekly.Single Agent
• Any drug of L-CHOP can be used as a 
single agent, but expect shorter overall 
survival than multiagent. • Doxorubicin 
(Adriamycin) 30 mg/m2 IV every 3 weeks (1 
mg/kg for dog <15 kg) 5–6 treatments. 
• CCNU (lomustine) 70 mg/m2 PO every 3 
weeks, prednisone 2 mg/kg PO daily. 
• Tanovea (rabacfosadine) 1 mg/kg IV every 
3 weeks, prednisone 1 mg/kg PO EOD.
Low-Grade Lymphomas
• Chlorambucil (Leukeran) 6 mg/m2 PO 
daily for 7–14 days, prednisone 2 mg/kg PO 
daily. Consider reducing chlorambucil dose to 
3 mg/m2 for maintenance. • CCNU 
(lomustine) as above.
• Doxorubicin—use dexrazoxane (Zinecard) 
in conjunction with doxorubicin or substitute 
epirubicin for dogs with cardiac issues. 
Always use a freshly placed catheter when 
administering IV doxorubicin. 
• l-Asparaginase and doxorubicin—pretreat 
with diphenhydramine 1–2 mg/kg SC, 15 
minutes before administration. • Cytoxan—
pretreat with furosemide 2 mg/kg to prevent 
sterile hemorrhagic cystitis.
Most chemotherapy drugs have overlapping 
GI and bone marrow toxicities. Consider 
antidiarrheals (metronidazole, loperamide) 
and antiemetics (metoclopramide, maropi-
tant, ondansetron) to abrogate these effects.
• Many published rescue protocols have been 
reported; therefore, always consult with a medical 
oncologist. • MOPP—mechlorethamine 
(Mustargen), vincristine, procarbazine, and 
prednisone. • DMAC—dexamethasone, 
melphalan, actinomycin-D, and cytosine 
arabinoside. • CCNU ± l-asparaginase, 
prednisone, or DTIC (dacarbazine). 
• Mitoxantrone alone or doxorubicin/DTIC.
  FOLLOW-UP
• Weekly physical examination to assess 
response and CBC to gauge bone marrow 
toxicities. • If neutropenia (neutrophils 
<1,500 cells/mm3) is noted, reduce dosage 
(20–25%) of drug when given again.
• Reversible neutropenia 7–10 days after 
chemotherapy. • Temporary vomiting, 
diarrhea, and anorexia 3–5 days after 
chemotherapy. • Alopecia in certain dog 
breeds that require grooming (poodle, shih 
tzu, etc.). • Febrile neutropenia (treated with 
broad-spectrum antibiotics).EXPECTED COURSE AND PROGNOSIS
• >80% of dogs will go into clinical remission 
during the first month of induction chemo -
therapy. • Stage, substage, and immuno -
phenotype are important prognostic indicators. 
• Expect median survivals of ~12–14 months 
and ~6–9 months in dogs with high-grade 
multicentric B- and T-cell LSA, respectively, 
when treated with a multiagent protocol. Dogs 
with indolent disease can live years. GI, 
mediastinal (T-cell ± hypercalcemia), and 
mycosis fungoides are associated with poorer 
response to treatment and an overall shorter 
survival time. • Autologous BMT can cure 
~33% of dogs with B-cell LSA and ~15% of 
dogs with T-cell LSA. The cure rate of 
allogeneic BMT is currently unknown.
T reatment of pregnant dogs is usually 
SYNONYMS
• Lymphosarcoma. • Malignant lymphoma.
SEE ALSO
• DLBCL = diffuse, large B-cell lymphoma.
• FL = follicular lymphoma.
• GI = gastro  intestinal.
• LN = lymph node.
• LSA = lymphoma.
• MZL = marginal zone lymphoma.
• PTCL-NOS = peripheral T-cell lymphoma—  
not otherwise specified.
• TZL = T-zone lymphoma.
Bienzle D, Vernau W. The diagnostic 
assessment of canine lymphoma: implica-
tions for treatment. Clin Lab Med 2011, 
31(1):21–39.
Rassnick KM, McEntee MC, Erb HN, et al. 
Comparison of 3 protocols for treatment 
after induction of remission in dogs with 
lymphoma. J Vet Intern Med 2007, 
21(6):1364–1373.
Author  Steven E. Suter
Wallace B. Morrison.
available online(continued)  Lymphoma—Dogs

858  Blackwell’s Five-Minute Veterinary Consult  
LLymphoma, Cutaneous Epitheliotropic
  BASICS
OVERVIEW
• Cutaneous epitheliotropic lymphoma—
most common form of cutaneous T-cell 
lymphoma.
• An uncommon malignant neoplasia of dogs 
and cats.
• Sézary syndrome—rare; cutaneous lesions, 
invasion of peripheral lymph nodes by 
neoplastic lymphocytes, and leukemia occur 
simultaneously.
• Pagetoid reticulosis—rare; the lymphoid 
infiltrate is confined to the epidermis and 
adnexal structures in the early stages of the 
disease and extends to the dermis in the late 
stages.
• Systems affected—hemic/lymphatic/
immune; skin/exocrine.
• Synonyms—mycosis fungoides, lymphoma 
epidermotropic.
• Dogs and cats—most common in dogs.
• Age range 6–14 years; mean 8.6 years.
• No apparent breed or sex predilection.
SIGNS
• Chronic skin disease—months before 
• Rarely acute.
• Mimics other inflammatory dermatoses.
• Typically pruritic in dogs and variably 
pruritic in cats.
• Four clinical categories of presentation:
◦ Exfoliative erythroderma—generalized 
erythema, scaling, depigmentation, alopecia.
◦ Mucocutaneous—depigmentation, 
erythema, erosion, and ulceration affecting 
mucocutaneous junctions.
◦ T umoral—solitary or multiple erythematous 
and scaly plaques, nodules, and masses.
◦ Oral mucosal ulceration of gingiva, 
palate, and/or tongue.
• Lesions—typically throughout the skin; 
marked tendency for involvement of 
mucocutaneous junctions or oral cavity; 
lesions can be limited to the mucocutaneous 
junctions or oral mucosa.
• Exfoliative erythroderma; progression to the 
tumor stage is very rapid in dogs compared to 
humans.
• Mucocutaneous form and oral mucosa 
form: tend to merge with chronicity.
• Rarely nodules develop without a preexisting 
patch or plaque stage (d’emblee form).
• Nodular stage may occasionally progress to 
a disseminated form with lymph node 
involvement, leukemia, and rarely other 
organs.CAUSES & RISK FACTORS
Risk of development from chronic antigenic 
stimulation (including allergy) theorized.
  DIAGNOSIS
• Feline thymoma-associated exfoliative 
• Allergic or parasitic dermatitis.
• Erythema multiforme.
• Mucocutaneous pyoderma.
• Non-neoplastic stomatitis.
• Cutaneous neoplasia.
• Generally unremarkable if only the skin or 
mucosa is affected.
• Sézary cells—neoplastic lymphocytes (8–20 
μm) with convoluted nucleus and cerebriform 
appearance are present in peripheral blood of 
Sézary syndrome patients.
Skin biopsy—definitive diagnosis; sample 
multiple different-appearing lesions, avoid 
eroded/ulcerated and infected lesions.
• Infiltrate of neoplastic lymphocytes—into 
epidermis, hair follicle epithelium, and 
adnexa; distributed diffusely or as discrete 
Pautrier microaggregates.
• Dermal infiltrate—polymorphous; malignant 
lymphocytes may obscure the dermoepidermal 
junction; patch and plaque stages, limited to 
the superficial dermis; nodular stage, extends to 
the deep dermis and subcutis.
• Immunohistochemical tissue staining 
reveals a predominance of CD8+ cytotoxic 
T-cells (dogs).
  TREATMENT
• Grave prognosis—goal is to maintain a 
good quality of life.
• Therapy is rarely curative.
• Rarely, solitary nodules can be surgically 
excised.
• Total skin electron therapy or orthovoltage 
radiation: well tolerated, may be beneficial in 
• Lomustine (CCNU)—overall response rate 
of 82% with remission achieved in about 32% of cases (initial dose 60 mg/m2 PO; 
range 30–90 mg/m2 every 3–4 weeks for a 
mean of 3–5 treatments).
• Dacarbazine 1000 mg/m2—3 cycles report 
of remission in one dog with nodal 
• Pegylated liposomal doxorubicin—44% 
response rate in dogs (average dose, 1 mg/kg 
IV every 3 weeks).
• Combination protocol (cyclophosphamide, 
doxorubicin, vincristine, and prednisolone)—
partial to complete response in dogs that 
failed lomustine therapy.
• High-dose linoleic acid (e.g., safflower 
oil)—3 mL/kg orally twice weekly; good 
improvement in 7/10 dogs for up to 2 years.
• Topical chemotherapy—mechlorethamine 
(nitrogen mustard); some success in managing 
early lesions.
• Corticosteroids—topical and/or systemic 
may result in some symptomatic relief.
• Retinoids—isotretinoin 3 mg/kg/day or 
acitretin 2 mg/kg/day may be beneficial.
• Rabacfosadine—45% of dogs (5/11) had 
either complete remission or partial 
Management by veterinary oncologist or 
dermatologist recommended.
  FOLLOW-UP
• Average survival time for dogs depends 
upon stage of disease at diagnosis, therapeutic 
choice, and response to therapy; median 
6 months (range 1 month–2 years).
• Death is usually the result of euthanasia.
Rook KA. Canine and feline cutaneous 
epitheliotropic lymphoma and cutaneous 
lymphocytosis. Vet Clin North Am Small 
Anim Pract 2019, 49:67–81.
Author  Sheila M.F . Torres
Resnick

Canine and Feline, Seventh Edition  859
L BASICS
OVERVIEW
• Inherited disorders caused by partial or 
complete deficiency of a lysosomal enzyme or 
an enzyme-activator protein, which leads to 
intracellular accumulation (storage) of the 
substrate of that enzyme. • Storage prod-
ucts—proteins, carbohydrates, lipids, or a 
combination. •  Classes of diseases—pro-
teinoses, glycoproteinoses, oligosaccharidoses, 
sphingolipidoses, mucopolysaccharidoses.  
• Many different types reported in dogs and 
cats. •  Inheritance is autosomal recessive.
• Dog—German shepherd dog, German 
shorthaired pointer, English setter, beagle, Cairn 
terrier, bluetick hound, West Highland white 
terrier, Sydney silky terrier, English springer 
spaniel, Portuguese water dog, Japanese spaniel, 
Labrador retriever, American bulldog, Irish 
setter, mixed-breed dogs, many others. •  Cat—
Persian, Siamese, Korat, Balinese, domestic 
shorthair. •  Most affected animals <1 year old; a 
few adult-onset diseases described, with onset as 
late as 2 years old, or older.
SIGNS
• Vary with severity of the enzyme deficiency. 
• In certain diseases, carrier animals can be 
affected with a milder form of the disease.  
• Many organ systems are affected, but 
neurologic signs tend to predominate.
• Affected animals are normal at birth. •  Fail to 
thrive and may manifest skeletal malformations, 
particularly in the mucopolysaccharidoses.  
• Neurologic signs within the first few months 
of life suggest multifocal neurologic disease.
Physical/Neurologic Examination
• Cerebellar dysfunction common—intention 
tremors, nystagmus, dysmetria. •  Peripheral 
neuropathy occurs in some diseases—weakness, 
hyporeflexia or areflexia, muscle wasting. •  Other 
neurologic signs—ataxia; exercise intolerance; 
seizures; behavioral changes; visual deficits, 
deafness, stereotypical behaviors, proprioceptive 
deficits, tremors. •  Non-neurologic signs—may 
see organomegaly or skeletal malformations. • 
Ocular pathology in some diseases—corneal 
opacification, cataract formation.
• Genetic—deletion or mutation involving a 
single gene that causes an absolute or partial 
deficiency of a lysosomal enzyme or activator 
protein; deficient production of enzymes that 
do not have normal biologic activity.  
• Susceptible breed. DIAGNOSIS
• Metabolic encephalopathy—usually episodic 
clinical signs; results of CBC, biochemistry, 
and urinalysis often diagnostic. •  Toxicities—
acute onset of clinical signs; history of 
exposure. •  Cerebellar hypoplasia—onset at 
3–6 weeks of age; nonprogressive. •  Cerebellar 
abiotrophy—deficits limited to the cerebellum; 
may be difficult to differentiate in the early 
stages without specific tests. •  Prenatal or 
neonatal infections (especially viral) resulting 
in meningoencephalomyelitis—differentiated 
by CSF analysis; may be other signs, such as 
chorioretinitis. •  Metabolic diseases—espe -
cially organic and amino acidurias.
• Regular blood smears and CSF analysis—
cytoplasmic vacuolation of leukocytes caused 
by accumulation of storage products is 
present in some cases. •  Urine—may find 
abnormal accumulation of substances (e.g., 
oligosaccharide in α-mannosidosis).
IMAGING
• Radiography—bony malformation may be 
present in diseases in which skeletal pathology 
is a feature (e.g., mucopolysaccharidoses).  
• MRI—used in one case to reveal diffuse 
white matter pathology in the brain of a dog 
with globoid cell leukodystrophy.
• Molecular genetic testing—available for the 
diagnosis of many lysosomal storage diseases; 
may be used to identify potential carriers.  
• Aspirates or biopsies of parenchymal organs, 
particularly the liver and spleen—may reveal 
intracellular storage material. •  Biochemical 
tests—diagnosis may be made by demonstrat-
ing low enzyme activity or presence of 
accumulated substrate or metabolic interme-
diates in preparations of serum, brain, viscera, 
leukocytes, or skin fibroblasts.  
• Electromyography and nerve conduction 
studies—abnormal in diseases in which 
peripheral neuropathy or myopathy is a 
feature. •  Biopsy of peripheral nerve or 
skeletal muscle—may demonstrate specific 
pathology.
 TREATMENT
• Outpatient—unless severe deficits preclude 
nursing care at home. •  Activity—restrict to 
safe areas; avoid stairs. •  Diet and fluids—
ensure proper intake in patients often 
debilitated; parenteral fluid therapy and enteral or parenteral nutritional support may 
be needed with severe disease. •  Bone 
marrow transplantation—used experimentally 
with some success. •  Gene therapy—area of 
intense research that may offer hope for 
specific treatment. •  Enzyme replacement 
therapy—intrathecal enzyme replacement has 
shown some efficacy in an experimental 
setting. • Primary treatment—preventive; 
control of breeding; genetic counseling. 
• Patients may be at risk of developing 
secondary infection; initiate appropriate 
treatment if infection develops.
N/A
  FOLLOW-UP
• Progressive; ultimately fatal. •  Pedigree 
analysis—useful in diagnosis; important for 
identification of potential carrier animals.
Bradbury AM, Gurda BL, Casal ML, et al. A 
review of gene therapy in canine and feline 
models of lysosomal storage disorders. Hum 
Gene Ther Clin Dev 2015, Feb 11.
115–121.
Mellersh C. Inherited neurologic disorders in 
the dog: the science behind the solutions. 
44:1223–1234.
Skelly BJ, Franklin RJM. Recognition and 
diagnosis of lysosomal storage diseases in 
the cat and dog. J Vet Intern Med 2002, 
16:133–141.
Author  Stephanie KubeLysosomal Storage Diseases

860  Blackwell’s Five-Minute Veterinary Consult  
M  BASICS
OVERVIEW
• Malassezia pachydermatis  is a lipid-loving 
commensal of the skin, ears, and mucocuta-
neous areas; can overgrow causing dermatitis, 
cheilitis, and otitis externa.
• T ransformation from harmless commensal 
to pathogen related to allergy, seborrheic 
conditions, and congenital and hormonal 
factors.
• Systems affected—skin/exocrine.
• Dog—any breed; West Highland white 
terrier, poodle, basset hound, cocker spaniel, 
and dachshund predisposed.
• Cat—less common; associated with internal 
neoplasia in aged cats; affects all breeds; 
young Rex cats predisposed.
SIGNS
• Pruritus variable; erythema, alopecia, 
scale, and greasiness of lips, ears, feet, 
axillae, inguinal area, and ventral neck; 
malodor.
• Hyperpigmentation and lichenification—
• Concurrent black waxy to seborrheic 
otitis—frequent.
• Frenzied facial pruritus—uncommon but 
characteristic.
• Often an allergy history that worsens and 
develops glucocorticoid tachyphylaxis.
• Concurrent bacterial folliculitis, hypersensi-
tivity, endocrine and seborrheic dermatitis.
• High humidity and temperature—may 
increase the frequency.
• Concurrent hypersensitivity disease 
• Seborrheic dermatitis (young dogs)—in 
• Endocrinopathy—suspected predisposing 
factor.
• Genetic factors—in predisposed dog 
breeds. In Rex cats: genetic factors of the skin 
and/or their predisposition to a mast cell 
abnormality called urticaria pigmentosa are 
speculative risk factors.
• Concurrent increase of Staphylococcus 
pseudintermedius  folliculitis—with over -
growth of both; treatment of one produces 
partial resolution and unmasks the other.
• Cats have a young and an adult-age disease 
that can be allergy-associated. Aged cats—
Malassezia  dermatitis associated with 
thymomas and carcinomas of the pancreas 
and liver.  DIAGNOSIS
Demonstration of excessive numbers of the 
organism on diseased skin, and significant 
improvement following removal of the yeast.
• Allergic dermatitis—including flea allergy, 
atopy, and cutaneous adverse reaction to food.
• Superficial bacterial folliculitis.
• Primary and secondary seborrhea (keratini-
zation defect).
• Acanthosis nigricans—dachshund.
Normal unless affected by underlying cause.
• Fungal culture—press contact plates onto 
the affected skin surface; incubate for 3–7 
days; count the distinctive yellow or buff, 
round, domed colonies (1–1.5 mm); provides 
semi-qualitative data.
• Nonquantitative culture methods—no value 
because Malassezia  is a normal commensal.
• Skin cytology—touch, cotton swab, or 
cellophane tape preparation; apply stain as a 
drop directly onto the slide (yeast may wash off 
during staining); pass a flame under the slide 
to improve stain penetration and visualization.
• Greasy and/or scaly areas most likely to 
produce positive results.
  TREATMENT
• Identify and treat predisposing factors or 
diseases.
• Topical therapy—yeast is principally 
located in the stratum corneum.
• Shampoo treatment—to remove scale and 
exudation: miconazole and chlorhexidine 
shampoo most effective; selenium sulfide 
shampoo less effective but useful; twice-
weekly treatments.
• Other topical antifungal agents (e.g., 
ketoconazole) also of value if given with 
suitable systemic medications.
• Alternative combinations—topical 
keratolytic shampoo treatment with systemic 
antiyeast and antibacterial drugs.
• Localized cases—may respond to lotions 
containing imidazole compounds.• Ketoconazole 10 mg/kg q24h, fluconazole 
10 mg/kg q24h, or itraconazole 5 mg/kg 
q24h for 2–4 weeks in widespread or chronic 
lichenified cases.
• Other imidazoles also effective.
• Topical antimicrobial antibacterial 
shampoo—to maintain remission in chronic 
cases.
Ketoconazole may cause hepatic reaction; 
masks signs of hyperadrenocorticism and 
interferes with adrenal function tests due to 
blocking of cortisol production (via inhibi-
tion of P450) in the adrenal gland; may affect 
metabolism of other medications; contraindi-
cated in cats. Azole-tolerant strains of 
Malassezia pachydermatis have been 
  FOLLOW-UP
• Physical examination and skin cytology—
after 2–4 weeks, to monitor therapy.
• T reat until only rare organisms can be 
demonstrated or 7 days after a complete 
response is achieved.
• Pruritus and odor—usually noticeably 
improved within 1 week.
• Recurrences—common when underlying 
dermatoses are not well controlled; regular 
bathing with antifungal antibacterial 
shampoo combinations helps decrease 
Ketoconazole contraindicated.
Bond R, Morris DO, Guillot J, et al. Biology, 
diagnosis and treatment of Malassezia  
dertmatitis in dogs and cats: Clinical 
Consensus Guidelines of the World 
Association for Veterinary Dermatology. 
Vet Dermatol 2020, 31:73–77.
2018.
Author  Kenneth V. Mason
ResnickMalassezia Dermatitis

Canine and Feline, Seventh Edition  861
M  BASICS
OVERVIEW
• Name based on histologic features of 
fibroblast- and histiocyte-like cells.
• A group of primitive pleomorphic 
m esenchymal neoplasms, but definitive 
cellular origin unknown; likely possibilities 
include fibroblasts, histiocytes, and 
u ndifferentiated mesenchymal cells.
• Several histologic variants.
• Storiform-pleomorphic and giant cell—two 
major variants; both locally invasive; firm, 
subcutaneous, or visceral masses on examination.
• Despite previous reports to the contrary, 
metastatic potential in dogs appears to be 
moderate to high.
• Have been reported as injection site-related 
sarcomas of cats.
• More commonly reported in cats than in dogs.
• Similar biologic behavior in both species.
• Mean age—cats: 9 years (range 2–12 years); 
dogs: 8 years (range <1–10 years).
• No proven breed or sex predilection, 
although flat-coated retrievers, Rottweilers, 
and golden retrievers appear overrepresented 
and may be predisposed.
SIGNS
• Anorexia, weight loss, and lethargy may occur.
• Depend on site of involvement.
• Firm, invasive tumor arising in subcutane-
ous tissue.
• May exhibit deep extension into underlying 
skeletal muscle.
• May develop adjacent to bone and induce 
bone destruction and proliferation.
• Most common sites—dorsal thoracic and 
scapular area, limbs, and pelvic region.
• May also be a primary splenic tumor in 
dogs; palpable splenomegaly may be found.
• Distant metastasis—common.
• Unknown.
• Can be induced with carcinogens in 
laboratory animal species.
• Injection sites in cats.
  DIAGNOSIS
• Other forms of soft tissue sarcoma (e.g., 
fibrosarcoma, leiomyosarcoma).
• Chondrosarcoma.
• Osteosarcoma (extraskeletal).
• Liposarcoma.
• Peripheral nerve sheath tumors.• Histiocytic diseases, such as histiocytic 
sarcoma or systemic histiocytosis.
• CBC—may vary; may be normal; may see 
regenerative or nonregenerative anemia.
• Biochemistry—variably abnormal.
• Urinalysis—usually normal.
Cytologic examination of aspirate—may 
reveal histiocyte- and fibroblast-like cells.
IMAGING
• Radiography—reveals soft tissue dense 
mass; may note bone proliferation or 
destruction.
• Three-view thoracic radiography to check 
for lung metastasis.
• MRI or CT may be superior for delineating 
extent of tumor invasion into surrounding 
tissues.
• Ultrasonography may detect abnormalities 
consistent with abdominal metastasis (most 
common in lymph nodes and liver).
Histologic examination of biopsy specimen—
necessary for definitive diagnosis.
• Classification—considerable debate exists 
among pathologists regarding use of the term 
maligant fibrous histiocytoma, which may 
account for the apparent differences in 
behavior reported in the literature.
• Storiform-pleomorphic (may be called 
inflammatory) and giant cell (also called 
osteoclast-like) are the two major variants 
reported. Myxoid variant also described.
• Many are histologically high grade.
• Specialized immunohistologic stains, such 
as CD18, vimentin, desmin, alpha-smooth 
muscle actin, extra domain 1 (ED1), and/or 
azan (for collagen) may aid classification. 
Definitive staining patterns have not been 
clearly identified.
• Recent report of considerable overlapping 
histopathologic characteristics with histiocytic 
diseases in the splenic form.
  TREATMENT
• Surgical excision—difficult owing to local 
invasive nature; recurrence rate is high.
• Amputation of an affected limb—may be 
appropriate, however considerable metastatic 
risk; thoracic and abdominal radiographs and 
abdominal ultrasound critical for evaluating 
detectable metastasis before surgical treatment.
• Radiotherapy may be helpful as adjuvant 
treatment for localized tumor not amenable 
to complete surgical resection. Expected local 
tumor control rates may be similar to other 
high-grade soft tissue sarcomas.  MEDICATIONS
Chemotherapy—may be helpful in residual, 
high-grade tumor or metastatic disease 
setting; doxorubicin-based protocols are most 
popular (dose for canine patients >10 kg, 30 
mg/m2 IV every 3 weeks; patients <10 kg, 1 
mg/kg IV every 3 weeks).
N/A
  FOLLOW-UP
Reexamination—metastatic potential would 
suggest physical examination and possible 
imaging; monthly for 3 months, then every 3 
months thereafter.
dermatitis and alopecia) may be expected 
with radiation therapy, and consultation with 
a radiation oncologist is recommended 
effects.
Fulmer AK, Mauldin GE. Canine histiocytic 
neoplasia: an overview. Can Vet J 2007, 
48:1041–1050.
Consulting Editor  Timothy M. FanMalignant Fibrous Histiocytoma

862  Blackwell’s Five-Minute Veterinary Consult  
MMalocclusions—Skeletal and Dental
  BASICS
OVERVIEW
• Malocclusion is any deviation from normal 
occlusion due to abnormal positioning of a 
tooth (dental malocclusion) or due to 
asymmetry or deviation of bones that support 
the dentition (skeletal malocclusion).
• Ideal occlusion:
◦ Maxillary incisors positioned rostral to 
the mandibular incisors.
◦ Mandibular canine is inclined labially 
and bisects the space between the opposing 
maxillary third incisor and canine.
◦ Maxillary premolars do not contact the 
mandibular premolars; mandibular 
premolar crowns are positioned lingual to 
the maxillary premolars; mandibular 
premolar crown cusps bisect the inter­
dental spaces rostral to the corresponding 
maxillary premolar.
◦ Maxillary fourth premolar mesial cusp is 
lateral to the space between the mandibular 
fourth premolar and first molar.
Terms of Malocclusion (American 
Veterinary Dental College Nomenclature)
• Neutroclusion (Class 1)—a normal 
rostral–caudal relationship of the maxillary 
and mandibular dental arches with 
malposition of one or more individual teeth 
(dental malocclusion); rostral (anterior) 
crossbite; mesioversion (“lance tooth”), 
linguoversion (“base ­narrow” mandibular 
canine), and caudal (posterior) crossbite.
• Mandibular distoclusion (Class 2)—an 
abnormal rostral–caudal relationship in which 
the mandibular arch occludes caudal to its 
normal position relative to the maxillary arch 
(skeletal malocclusion).
• Mandibular mesioclusion (Class 3)—an 
the mandibular arch occludes rostral to its 
normal position relative to the maxillary 
• Asymmetrical skeletal malocclusion—
maxillary–mandibular asymmetry that can occur 
in a rostro ­caudal direction (unilateral abnormal 
relationship), in a side ­to­side direction (loss of 
midline alignment), or in a dorso ­ventral 
direction with abnormal vertical space between 
opposing dental arches (open bite).
Species
Breed predilection for certain malocclusions, 
some within breed standards.
Malocclusion usually apparent after eruption 
of teeth (permanent or deciduous).SIGNS
• Vary greatly according to type, extent, and 
consequent injuries caused by the malocclusion.
• May be associated with open or closed bites 
or overcrowding of the teeth.
• Periodontal disease—from crowding or 
misalignment of teeth.
• Soft tissue defects—from traumatic tooth 
contact; may be seen in the floor of the 
mouth and palate; palatal trauma may 
eventually result in oronasal fistula formation.
• Fractures or attrition (wear) of teeth—may 
result from improper tooth contact.
Class 1 Malocclusions
• Rostral crossbite—palatally displaced 
maxillary incisor(s) or labially displaced 
mandibular incisor(s); level bite—maxillary 
and mandibular cusps contact directly.
• Linguoversion base ­narrow canines—tips of 
mandibular canines touch palate lingual to 
normal contact point, just labial to the 
diastema between corner incisor and maxillary 
canine (linguoversion).
• Lance teeth—mesioversion of maxillary 
canine(s); the diastema between the corner 
incisor and this canine is often diminished 
and may force the mandibular canine into an 
abnormal position. Dolichocephalic breeds 
(e.g., shelties and collies).
• Caudal crossbite—one or more mandibular 
cheek teeth buccal to maxillary teeth; more 
common in dolichocephalic breeds (e.g., 
collies, shelties, some sight hounds).
• Congenital or hereditary factors—skeletal 
malocclusions (Classes 2, 3, and 4) and breed 
• Impediment to tooth eruption—operculum; 
retention of soft tissue covering.
• Delayed eruption of deciduous or 
permanent teeth.
• Retention (persistent) or delayed loss of 
deciduous teeth; permanent mandibular 
canines (and most other teeth) will erupt 
lingual to persistent deciduous teeth; the 
permanent maxillary canine will erupt rostral 
to the deciduous tooth.
• T raumatic injury affecting the jaws or teeth.
Risk Factors
Hereditary predispositions.
  DIAGNOSIS
• Tooth displacement—due to trauma, oral 
masses, or other causes.
• Mechanical block—due to jaw fractures, 
luxated or subluxated teeth, or foreign bodies 
causing open bite.
• Examine breed standards to determine what 
might be acceptable for the breed.CBC/BIOCHEMISTRY/URINALYSIS
IMAGING
• Oral photography—pre ­, peri ­, and 
post­therapy.
• Intraoral radiography—to evaluate roots 
and abnormalities, jaw anatomy, root 
maturity.
• Complete oral examination to assess other 
oral abnormalities, including persistent 
deciduous teeth.
• Impressions and models—for evaluation 
and appliance production.
  TREATMENT
• The accurate assessment of abnormalities 
of occlusion will help determine if 
treatment is warranted and what treatment 
is appropriate.
• Extraction of affected teeth can many times 
be an effective alternative to more classic 
orthodontic treatments.
• If the bite is functional and nontraumatic 
to the animal, treatment may not be 
necessary. Extraction (or crown reduction 
with pulp capping) of offending teeth can 
often be an effective alternative to more 
classic orthodontic treatments. Orthodontic 
treatment is usually based on prevention of 
improper contact trauma, wear, or injury to 
hard or soft tissues, and should only be 
performed by a trained individual.
Diet
Soft diet with appliances.
Home Care with Appliance
• Examine the appliance twice daily.
• Flush the mouth with an oral hygiene 
solution or gel.
• Prevent chewing of items and provide a soft 
diet until the appliance is removed.
Permanent Tooth Class 1 Malocclusion
• T reatment primarily involves tipping 
movements of the teeth, although extrusion 
may be required to provide proper retention.
• Rostral crossbite—correction for esthetics 
• Linguoversion mandibular canine 
teeth—prevention of contact trauma, pain 
and discomfort, and oronasal fistula 
◦ The maxillary diastema must be 
sufficient for the mandibular canine to fit; 
natural retention once corrected.
◦ Early intervention with manual 
manipulation or “ball therapy” for newly

Canine and Feline, Seventh Edition  863
Merupting teeth may influence a more buccal 
position.
◦ A hard rubber ball is placed in the 
mouth to help “slide” the canines laterally; 
two to three times daily, a few minutes at 
a time.
◦ Gingivoplasty in the diastema may release 
the tooth if there is minimal maxillary 
mucosal contact.
◦ A composite crown extension can help 
splay the tip buccal to the gingival margin.
◦ More severe cases may require an 
orthodontic appliance (incline plane), to be 
handled by a specialist.
◦ Mandibular canine extraction or crown 
reduction with vital pulp therapy.
• Maxillary canine mesioversion (Lance 
tooth): complicated movement; handled by 
specialist.
• Caudal crossbite—in traumatic situations, 
extraction of one of the offending teeth; 
orthodontic correction would be long and 
tedious.
Permanent Tooth Class 2, 3, 
and Asymmetrical Malocclusion
• If malocclusion is functional and 
nontraumatic, treatment may not be 
• May require advanced orthodontic and 
surgical procedures by a specialist.
Deciduous Tooth Class 1 Malocclusion
Careful and gentle extraction of the 
maloccluded deciduous tooth (interceptive 
orthodontics) in hopes that the permanent 
tooth will erupt in the appropriate position; 
when performed at least 4 weeks prior to 
permanent tooth eruption, success rate >80% 
is not uncommon.
Deciduous Tooth Class 2, 3, and 4 
Malocclusion
maloccluded deciduous tooth in hopes that 
the short jaws will be released from the bite 
interlock, allowing it to grow (if the genetic 
potential is present), performed at least 6 
weeks prior to permanent tooth eruption, 
success rate <20% is common.  FOLLOW-UP
• For the corrected occlusion to be stable, it 
needs to be self ­retaining, or it may tend to 
revert to malocclusion; examine at 2 weeks, 2 
months, and 6 months after the treatment is 
complete to see if desired outcome is stable.
• Radiographs at 6 months post therapy for 
radiographs to evaluate roots and teeth for 
any changes.
• Selective breeding based on preferred breed 
characteristics.
• Careful monitoring of deciduous and 
permanent tooth eruption for early detection 
and treatment, if required.
• Deciduous tooth extractions—potential 
injury to underlying permanent tooth buds; 
injuries may result in tooth buds dying, teeth 
becoming nonvital as they erupt, root 
dysplasia or dilaceration, crown enamel 
hypoplasia, or hypomineralization.
• Orthodontic movement of permanent 
teeth—several conditions may result, 
including movement of anchor teeth, root 
resorption, root ankylosis, or nonvitality of 
the tooth; these conditions are uncommon 
in properly managed orthodontic 
• Course of treatment may vary with the type 
of malocclusion and the animal’s nature and 
habits (e.g., inappropriate chewing).
• Generally, most cases take 1–7 months for 
movement and retention phase, depending on 
severity and if extrusion of tooth/teeth is 
required for stabilization of the bite. Prognosis 
is good to excellent in most treated patients.
• Prognosis is fair to good in most untreated 
malocclusions.
• Complications in untreated cases—periodontal 
disease; attrition or fractures of teeth; trauma to 
soft tissues; oronasal fistula formation; drying or 
desiccation of exposed tooth surfaces, resulting in beige to brown discoloration.
• Some cases do not need or require 
orthodontic intervention; only routine 
observation for early detection and treatment of 
any secondary complications (e.g., periodontal 
disease, worn or chipped teeth) is advised.
• Lack of head symmetry.
• Oral soft tissue trauma.
• Chipped teeth.
• Desiccation of exposed tooth surfaces.
Although animals have the medical right to as 
functional and correct an occlusion as can be 
reasonably provided by therapy, animal club 
rules, professional association principles, and 
state and national laws may conflict with an 
animal’s right to proper medical therapy. Some 
kennel club rules disqualify animals with 
modification to natural appearance (with 
certain exceptions), and owners should be 
made aware of this. If hereditary involvement 
is suspected, inform the owner. If treatment is 
being considered, the owner or agent should 
acknowledge his or her responsibility to 
inform anyone who has the right to know of 
such alterations. Additionally, the possibility 
of removing the animal from the genetic pool 
by appropriate methods should be discussed.
hthttps://avdc.org/avdc ­nomenclature/ 
(Accessed July 27, 2020).
NJ: Wiley ­Blackwell, 2019.
available online(continued)  Malocclusions—Skeletal and Dental

864  Blackwell’s Five-Minute Veterinary Consult  
M  BASICS
OVERVIEW
Benign enlargement of one or more 
m ammary glands.
• Young, intact, cycling, or pregnant queens.
• Cats of either gender after gonadectomy 
(rare in tom).
• Cats of either gender that are receiving 
exogenous progestogen (e.g., megestrol acetate).
• Less often in older (9–12 years) pregnant 
queens.
SIGNS
• Localized or diffuse rapid (2–5 weeks) 
enlargement of one or more mammary glands.
• Firm and nonpainful masses in uncompli-
cated cases.
• No concurrent signs of systemic illness.
• Exaggerated proliferation secondary to an 
endogenous progesterone influence (pregnancy, 
pseudopregnancy) or exogenous progestogens 
(megestrol or medroxyprogesterone acetate).
• May develop after gonadectomy; pa  thogenesis 
may involve progesterone, growth hormone, 
prolactin, insulin-like growth factors. Suspect 
ovarian remnant syndrome.
• Reported in one male with adrenocortical 
carcinoma producing steroid hormones.
  DIAGNOSIS
• Mastitis—lactating queen; mammary 
glands erythematous and painful; systemic 
illness with fever and immature neutrophilia; 
inflammatory cells and bacteria in fluid 
expressed from the affected gland(s).
• Mammary neoplasia—old queens (>6 years); 
gross appearance may be indistinguishable; 
irregular shape and margins, heterogeneous 
echogenicity on ultrasound; differentiated by 
biopsy or fine-needle aspirate of affected tissue.
Normal; leukocytosis possible if secondary 
mastitis present.
Progesterone analysis—confirm exposure or 
IMAGING
• T ransabdominal ultrasonography—to rule 
out pregnancy.
• Ultrasonography of affected gland(s)—
homogeneous parenchyma, round or oval 
with regular margins.
• Cytologic examination of fluid expressed 
from affected glands—noninflammatory.• Fine-needle aspirates of affected glands 
may help to diagnose neoplasia and 
• Excisional biopsy—benign fibroglandular 
proliferation with no inflammation or 
necrosis.
  TREATMENT
• Hyperplasia owing to high endogenous 
progesterone—regresses when progesterone 
falls at the end of false pregnancy or gestation; 
consider ovariohysterectomy if preservation of 
fertility is not desired.
• Hyperplasia owing to exogenous proges  - 
tagens—regresses when medication is 
• Hyperplasia developing after gonadec-
tomy—suspect ovarian remnant; surgical 
removal of remnants indicated.
• In uncomfortable animals, may attempt 
progesterone receptor blockers (aglepristone), 
prolactin inhibitors (bromocriptine, 
cabergoline), testosterone.
• Mastectomy, systemic antibiotics, or 
supportive care may be needed with 
• Bromocriptine mesylate 0.25 mg (per cat) 
PO q24h for 5–7 days; not approved for use 
in cats; may cause nausea. Can divide daily 
dose q12h to decrease nausea.
• Metoclopramide 0.2 mg/kg PO q6–8h for 
nausea.
• Cabergoline 5 μg/kg PO q24h for 5–7 days.
• Aglepristone 10–15 mg/kg SC on 2 
consecutive days or 20 mg/kg SC once a 
week until resolution; not approved for use 
in cats, not readily available in the United 
States.
• Testosterone cypionate or testosterone 
enanthate 2 mg/kg IM once; not approved 
for use in cats.
• Aglepristone—pregnant animals will 
abort. May see dermatitis at the site of 
injection.
• Dopamine agonists—pregnant animals will 
abort; may cause vomiting.
  FOLLOW-UP
• Remission within 4 weeks after the end of 
pseudopregnancy or gestation, withdrawal of progestins, ovariectomy, or aglepristone 
• Unknown likelihood of recurrence in cats 
left intact.
• Unknown correlation with other abnormal 
conditions of the reproductive tract.
Fertility not affected after aglepristone 
SEE ALSO
Ovarian Remnant Syndrome.
Burstyn U. Management of mastitis and 
abscessation of mammary glands secondary 
to fibroadenomatous hyperplasia in a 
primiparturient cat. J Am Vet Med Assoc 
2010, 236:326–329.
Gimenz F , Hecht S, Craig LE, et al. Early 
detection, aggressive therapy: Optimizing 
the management of feline mammary masses. 
J Feline Med Surg 2010, 12:214–224.
Görlinger S, Kooistra HS, van den Borek A, 
et al. T reatment of fibroadenomatous 
hyperplasia in cats with aglepristone. J Vet 
Intern Med 2002, 16:710–713.
Hayden DW, Johnston SD, Krang DT, et al. 
Feline mammary hypertrophy/fibroad-
enoma complex: clinical and hormonal 
aspects. Am J Vet Res 1981, 42:1699–1703.
Disorders of the mammary glands of the 
queen. In: Canine and Feline 
Saunders, 2001, pp. 474–485.
Authors  Maria Soledad Ferrer and Lynda 
M.J. Miller
Consulting Editor  Erin E. RuncanMammary Gland Hyperplasia—Cats

Canine and Feline, Seventh Edition  865
MMammary Gland Tumors—Cats
  BASICS
Malignant and benign tumors of the 
mammary glands in cats.
• The majority of mammary gland tumors are 
malignant (85–95%) and tend to have an 
aggressive biologic behavior. Most malignant 
mammary tumors are adenocarcinomas; 
sarcomas are rare. • Exposure to ovarian 
hormones and exogenous progestin increases 
risk of mammary tumor development. Intact 
cats have a 7-fold increased risk of developing 
mammary tumors as compared to spayed cats. 
Spaying cats prior to 1 year of age greatly 
reduces risk of mammary tumor development. 
• While less common at diagnosis, pulmonary 
metastasis occurs in up to 80% of cats. Regional 
lymph node metastasis is common at diagnosis 
and may occur in up to 45% of cats. At 
necropsy, metastasis is identified in >90% of 
cats; other sites of metastasis may include liver, 
spleen, kidney, adrenal gland, pleura, 
peritoneum, and bone. • Inflammatory 
mammary carcinomas are rare. These are 
anaplastic carcinomas with considerable 
inflammatory cell infiltrates, and are 
associated with extensive local ulceration, 
edema, and pain, as well as rapid metastasis.
• Reproductive—mammary glands. 
• Metastasis can affect any organ system, 
especially the respiratory and lymphatic systems.
GENETICS
The high incidence of mammary tumors in 
Siamese cats suggests a genetic component to 
this disease, but specific genes have not been 
identified to date.
• Third most common neoplasia in cats (after 
lymphoma and skin tumors). • The estimated 
incidence rate is 12.8–25.4 per 100,000 cats.
Species
Cat
• Domestic shorthair and longhair breeds are 
affected most commonly, but likely reflects 
the popularity of these breeds rather than a 
true predilection. • Siamese cats have twice 
the risk of other breeds for developing 
mammary tumors.
• Mean—10–12 years. • Range—9 months 
to 23 years; most are >5 years of age. 
• Siamese cats tend to be diagnosed with mammary tumors at a younger age (mean of 
9 years). • Male cats tend to be diagnosed 
with mammary tumors at an older age (mean 
of 12.8 years).
• Females predominate with only 1–5% of 
mammary carcinomas occurring in male cats. 
• While being intact increases the risk of 
mammary tumors (see Risk Factors), most cats 
diagnosed with mammary tumors are spayed.
SIGNS
• Most cats present for evaluation of a 
palpable ventral abdominal mass. • Cats with 
advanced metastatic disease may present for 
general signs of illness (e.g., lethargy or 
anorexia) or for signs attributable to a specific 
site of metastasis (e.g., dyspnea due to 
pulmonary metastasis or pleural effusion). 
• The duration of clinical signs can vary from 
days to several months.
• Mammary masses can be discrete or 
infiltrative, soft or firm. Smaller masses often 
are freely moveable, whereas larger masses can 
adhere to the underlying abdominal 
musculature. • The overlying skin is often 
intact for smaller tumors, but larger tumors 
may be ulcerated and inflamed. • The 
associated nipple may be inflamed and exude 
serous fluid. • Any gland can be affected, 
although the caudal two glands are affected 
more commonly. Left and right sides are 
affected with equal frequency. • Up to 60% 
of cats will have multiple tumors on the same 
and/or opposite mammary chain. • Axillary 
or inguinal lymphadenopathy (reactive or 
metastatic) may be present. • Cats with 
inflammatory carcinomas present with severe 
ulceration, erythema, pain, and edema in the 
ventral abdomen and pelvic limbs.
CAUSES
Unknown
• Compared to intact cats, those spayed at <6 
months of age or 6–12 months had a 91% 
and 86% risk reduction, respectively, for 
mammary carcinoma development, suggest -
ing that hormonal influence is significant. 
• There is no obvious protective effect when 
cats are spayed at >12 months of age. 
• Exogenous progestins (e.g., medroxy -
progesterone acetate) increase the risk of 
benign and malignant mammary tumor 
development in female and male cats. In one 
study, 8 of 22 male cats with mammary 
carcinomas had a history of exogenous 
progestin therapy. • Parity has not been shown 
to affect mammary tumor development.  DIAGNOSIS
• Fibroepithelial hyperplasia—especially in 
young (<2 years) intact female cats, and older 
or spayed cats receiving exogenous progestins. 
• Mastitis. • Other cutaneous or subcutane-
ous tumors. • Inguinal or axillary lymphad-
enopathy (reactive or neoplastic). • Inguinal 
hernia. • Large/prominent inguinal fat pad.
Coagulation profile recommended for cats with 
suspected inflammatory carcinomas due to the 
high incidence of secondary disseminated 
intravascular coagulopathy.
IMAGING
• Three-view thoracic radiographs are 
recommended to screen for pulmonary 
metastasis, pleural effusion, and/or sternal 
lymphadenomegaly. Pulmonary metastases 
commonly appear as ill-defined interstitial 
nodules or a diffuse pulmonary pattern, 
although well-defined interstitial nodules are 
seen occasionally. Malignant pleural effusion 
is common and can obstruct adequate 
visualization of pulmonary parenchyma. 
• Abdominal ultrasound is recommended to 
screen the medial iliac lymph nodes and other 
abdominal viscera for metastases. • Ultrasound 
also can be used to visualize nonpalpable 
axillary or inguinal lymph nodes, as well as to 
look for additional small masses within the 
• Cytology can be useful for ruling out other 
nonmammary malignancies. However, it is 
not useful for distinguishing between benign 
and malignant mammary masses. 
• Histopathologic evaluation is needed to 
reach a definitive diagnosis. Since most 
mammary tumors are malignant, this is 
usually performed on tissue removed during 
radical mastectomy (see T reatment). While 
not contraindicated, incisional biopsies are 
routinely recommended only for cats with 
advanced-stage disease that are not candidates 
for aggressive local surgery. • All tissue 
removed must be submitted for histopatho-
logic evaluation. This allows for the most 
accurate diagnosis, and also allows for 
evaluation of surgical margins for complete-
ness of excision. • The ipsilateral draining 
lymph nodes (axillary and inguinal) should be 
removed whenever possible and submitted 
separately for histopathologic evaluation, even 
if grossly normal. • Cytology of pleural fluid

866  Blackwell’s Five-Minute Veterinary Consult  
Mcan be useful for confirming intrathoracic 
• The most common histologic subtypes are 
tubulopapillary, cribriform, and solid 
carcinomas. • Histologic subtype has not 
consistently been shown to affect prognosis, 
but there is some evidence that tubulo -
papillary carcinomas carry a better prognosis. 
• T umor grade, based on degree of tubule 
formation, nuclear and cellular pleomorphism, 
and mitotic index, is predictive of survival 
after surgery. • Vascular and lymphatic 
invasion is associated with more advanced 
clinical stage and shorter disease-free interval 
after treatment. • Mammary sarcomas are rare 
but potentially slow to metastasize. • Benign 
histologic subtypes are uncommon and may 
include mammary adenomas, ductal 
adenomas, fibroadenomas, and intraductal 
papillary adenomas.
  TREATMENT
• Surgery is recommended for cats with gross 
disease confined to the mammary glands with 
or without regional lymph node involvement. 
• Adjuvant chemotherapy is recommended 
after the cat has recovered from surgery. 
• Chemotherapy can be used as a sole 
treatment modality for cats with nonsurgical 
local disease and/or distant metastasis, 
although long-term control would not be 
expected to be durable. • Radiation therapy 
has not been evaluated. • Palliative pain 
therapy is recommended for cats with 
nonresectable local disease or gross metastasis, 
or when definitive therapy is declined.
• Stress the benefits of early ovariohysterectomy 
(<6 months of age) in nonbreeding cats. 
• Stress the importance of early detection and 
aggressive treatment as small tumors (<2 cm) 
have a better prognosis.
• Radical mastectomy of the affected mam -
mary chain(s) is recommended. This signifi -
cantly reduces the risk of local tumor recurrence 
as well as recurrence in the lymphatic vessels 
coursing through the mammary tissue. 
• Bilateral radical mastectomy, regardless of 
tumor location, has been shown to lead to 
deceased rates of local tumor recurrence, new 
mammary tumor development, and metastasis 
as well as increased survival time as compared 
unilateral mastectomy. Mastectomies are 
usually staged 2–4 weeks apart as performing 
bilateral mastectomies in a single surgical 
procedure is associated with increased risk of incisional dehiscence and/or infections and, less 
commonly, respiratory difficulty. • The 
inguinal and (if possible) axillary lymph nodes 
should be removed at the same time, regardless 
if they are normal in size. • In cats with 
advanced metastatic disease, palliative local 
mastectomy can be considered to remove an 
ulcerated or infected tumor.
• Doxorubicin 25 mg/m2 IV every 3 weeks, 
alone or in combination with cyclophosph -
amide 100 mg/m2 IV or PO divided over 4 
days. • Mitoxantrone, carboplatin, and 
docetaxel might have activity. • Consult with 
an oncologist for current chemotherapy 
recommendations. • Palliative analgesics and 
antibiotics should be considered for cats with 
tumors that are painful and/or ulcerated.
Use doxorubicin with caution in cats with 
renal or hepatic insufficiency.
If you are unfamiliar with chemotherapy, 
consult an oncologist before administering.
  FOLLOW-UP
• Thorough physical examination conducted 
monthly for the first 3 months, then every 
2–3 months thereafter is recommended. 
Palpation of the previous incision line, the 
remaining mammary glands (if only unilateral 
radical mastectomy performed), and regional 
lymph nodes should be emphasized during 
examination. • Three-view thoracic radio -
graphs every 2–3 months for detection of 
metastases. • Consider abdominal ultrasound 
every 2–3 months to monitor for local lymph 
node metastasis.
Ovariohysterectomy prior to 6 months of age 
is associated with a 91% risk reduction in the 
development of mammary carcinoma.
Malignant pleural effusion may develop 
rapidly causing life-threatening dyspnea.
• Most cats die from local recurrence and/or 
metastasis. • T umor size is strongly predictive 
of prognosis. For tumors ≤2 cm in diameter 
median survival is >4.5 years (14 months in 
males), for tumors 2–3 cm it is 1–2 years 
(5–6 months in males), for tumors >3 cm it is 4–6 months (1–2 months in males). 
• Radical mastectomy significantly reduces 
the risk for local tumor recurrence. The 
impact on survival is not as consistent because 
of the high metastatic rate associated with this 
tumor. • In retrospective studies, adjuvant 
chemotherapy (doxorubicin with or without 
cyclophosphamide) has not consistently 
improved disease-free interval or survival. 
However, chemotherapy has proven efficacy 
against nonresectable and metastatic feline 
mammary tumors (gross disease), and given 
the high metastatic rate of these tumors 
adjuvant chemotherapy is still strongly 
recommended. • For cats with advanced-
stage disease treated with chemotherapy 
alone, response rates are around 50%. 
Survival times are 6–12 months for cats that 
do have a positive response to treatment, <6 
months for those that do not.
• Given the possible genetic contribution to 
this disease, particularly in Siamese cats, 
breeding affected cats is not recommended. 
• Chemotherapy is not recommended in 
pregnant queens, particularly during the early 
stages of pregnancy.
Gemignani F , Mayhew PD, Giuffrida MA, 
et al. Association of surgical approach with 
complication rate, progression-free survival 
time, and disease-specific survival time in 
cats with mammary adenocarcinoma: 107 
cases (1991–2014). J Am Vet Med Assoc 
2018, 252(11):1393–1402.
Morris J. Mammary tumours in the cat: size 
matters, so early intervention saves lives. J 
Feline Med Surg 2013, 15(5):391–400.
Novosad CA, O’Brien MG, McKnight JA, 
et al. Retrospective evaluation of adjunctive 
doxorubicin for the treatment of feline 
mammary gland adenocarcinoma: 67 cases. 
J Am Anim Hosp Assoc 2006, 42:110–120.
Overley B, Shofer FS, Goldschmidt MH, 
et al. Association between ovarihysterec-
tomy and feline mammary carcinoma. J Vet 
Intern Med 2005, 19:560–563.
acknowledge the prior contribution of Dennis 
B. Bailey. 
available onlineMammary Gland Tumors—Cats  (continued)

Canine and Feline, Seventh Edition  867
M BASICS
Benign or malignant tumors of the mammary 
glands in dogs.
• Estrogen can exert direct genotoxic effects 
on mammary epithelium leading to 
m utations and aneuploidy.
• Progesterone may increase growth 
hormone and growth hormone receptor 
expression by the mammary gland, leading to 
increased insulin-like growth factor-1 (IGF-1) 
which is associated with p  roliferation and 
survival.
• Most dogs develop multiple tumors due to 
entire mammary tissue exposed to sex hormones 
during puberty, i.e., “field carcinogenesis.”
• Mammary gland tumors are a continuum 
from benign to malignant.
• Obesity decreases sex hormone-binding 
globulin, leading to increased concentration 
of free estrogen.
• Metastasis—lymphatic, respiratory, skeletal, 
nervous, and other systems.
GENETICS
Germline mutations of BRCA-1  and - 2 and 
CDK5RAP2  genes reported in English 
springer spaniels.
Constitute 50–70% of all tumors in female 
dogs; 71% of all female beagles developed at 
least one mammary neoplasm.
Toy and miniature poodle, English springer 
spaniel, Brittany spaniel, cocker spaniel, 
English setter, boxer, English pointer, German 
shepherd dog, Maltese, Samoyed, schnauzer, 
Doberman pinscher, shih tzu, and Yorkshire 
terrier.
Uncommon in dogs <5 years; mean age 9–11 
years (malignant) and 7–9 years (benign).
SIGNS
• 70% of patients have multiple tumors.
• Caudal mammary glands more commonly 
affected.
• Discrete, well-circumscribed mass in 
systemically healthy patient.
• Inflammatory carcinoma—diffuse 
edematous, warm, painful mammary chains.
• Inflammatory carcinoma associated with 
distant metastasis and systemic illness.CAUSES
Unknown; likely hormonal.
• Age.
• Breed—more common in small breeds than 
in large breeds.
• Hormone influence (see Prevention/
Avoidance).
• Obesity during puberty increases risk. 
Underweight at 9–12 months of age 
associated with protective effect.
 DIAGNOSIS
• Lipoma.
• Mammary hyperplasia.
• Mastitis.
• Soft tissue sarcoma.
N/A
IMAGING
• Thoracic radiography may detect metastasis 
and three views are advised.
• CT is more sensitive for detection of 
pulmonary metastasis than are plain 
• CT lymphography could aid in the 
assessment of sentinel lymph node metastasis.
• Abdominal radiography may detect metastasis 
to regional lymph nodes or vertebrae.
• Abdominal sonography to evaluate for 
regional or distant metastasis.
• Fine-needle aspirate cytology—67.5–93% 
correlation with histopathology; 88% 
sensitivity and 96% specificity for 
malignancy.
• Fine-needle aspirate cytology of local lymph 
node(s).
• Histologic evaluation for definitive 
diagnosis. Request margin evaluation.
• There is a wide histologic spectrum of 
mammary tumors. Dogs may have concurrent 
benign and malignant tumors. Histologic 
examination of all excised masses is indicated.
• Histologic grading 1 (well-differentiated) to 
3 (poorly differentiated) based on tubule 
formation, nuclear pleomorphism, and 
mitotic index valid for epithelial tumors only.
• Stromal invasion, vascular/lymphatic 
invasion, and lymph node status important.
• Complex carcinoma is more common than 
simple carcinoma. TREATMENT
• Surgery—primary mode of treatment. 
Completeness of excision is prognostic.
• Chemotherapy—may be effective and 
indicated for patients with high risk of 
metastasis or recurrence: histologic high grade 
or subtype, lymphatic/vascular invasion, stage 
III or higher.
• Advise client that a mammary lump should 
be evaluated by a veterinary health professional.
• Inform client that early surgical interven-
tion is best.
• Advise ovariohysterectomy at time of tumor 
removal.
• Type of surgery determined by therapeutic 
intent: curative intent with wide excision; 
preventative with chain mastectomy; 
palliative intent for advanced disease.
• Consider age, tumor size, number of tumors, 
history of prior tumors, and clinical stage.
• Most patients with inflammatory 
c arcinoma are poor surgical candidates due to 
profound diffuse microscopic disease, 
advanced stage, systemic illness, and local 
• 58% of dogs treated with regional mastectomy 
will develop a new tumor in the ipsilateral chain; 
increased risk if initial tumor is malignant 
(>70%).
• Current recommendations for single tumor 
of unknown histology: wide excision to 
achieve complete removal is the adequate 
surgical “dose,” i.e., 2 cm lateral margins and 
1 fascial plane deep.
• Extirpation of the draining lymph node is 
advised. Immunohistochemistry may be 
indicated to detect occult metastasis.
• Ovariohysterectomy (OHE) concurrent with 
tumor removal may decrease the risk of relapse 
in dogs with grade 2, estrogen receptor-positive 
tumors, or dogs with increased presurgical 
serum estradiol.
• Remove tumor following abdominal closure 
if performing concurrent OHE to avoid 
tumor seeding of abdomen or incision.
updated information.
(NSAID) as sole adjuvant therapy.
• Doxorubicin 30 mg/m2 IV (dogs >15 kg) Mammary Gland Tumors—Dogs

868  Blackwell’s Five-Minute Veterinary Consult  
Mevery 21 days (maximum 6 treatments).
• NSAID ± chemotherapy for inflammatory 
Doxorubicin—myocardial failure.
Chemotherapy may be toxic; seek advice 
before treatment if you are unfamiliar with 
Doxorubicin—potential side effects include 
myelotoxicity, vomiting, diarrhea, and cardiac 
damage.
• Carboplatin, mitoxantrone, gemcitabine, 
fluorouracil (5-FU), cyclophosphamide have been 
reported with varying impact on clinical outcome.
• Perioperative desmospressin for grade 2–3 
carcinoma may improve survival.
• Tamoxifen—helpful in some humans with 
breast cancer; ineffective in dogs and has serious 
side effects (e.g., pyometra); do not use in dogs.
  FOLLOW-UP
Physical examination, abdominal sonography, 
and thoracic radiographs—1, 3, 6, 9, 12, 15, 
18 months after treatment, then every 6 
• Spayed before first estrous cycle—0.5% 
lifetime risk of developing tumor.
• Spayed before second estrous cycle—8.0% 
lifetime risk.
• Spayed after second estrus—26% lifetime risk.
• Spayed after 2.5 years of age—no sparing 
effect on risk.
• Infection or dehiscence with surgery.
• Myelosuppression with chemotherapy.
(DIC) with some (especially inflammatory 
carcinomas) types.
• 50–70% of canine mammary tumors are 
• 50% of malignant tumors metastasize.
• 58–70% of dogs will develop another 
tumor in the ipsilateral chain.
• T umor diameter is strong predictor of local 
recurrence and distant metastasis and is a 
negative, independent prognosticator of survival.• Lymph node status, histologic grade, and 
proposed World Health Organization 
(WHO) clinical stage (I–V) are most 
consistent prognostic factors.
◦ Stage I: T umor size <3 cm, no regional 
or distant metastasis—complete excision 
has excellent prognosis. 
◦ Stage II: T umor 3–5 cm, no regional or 
distant metastasis—complete excision has 
excellent prognosis. 
◦ Stage III: T umor >5 cm, no regional or 
distant metastasis—median survival 10 
months with surgery alone. 
◦ Stage IV: Any tumor size, lymph node 
metastasis, no distant metastasis—median 
survival time 5–10 months with surgery. 
◦ Stage V: Any tumor size, any lymph 
node status, evidence of distant 
m etastasis—median survival time  
<6 months.
• Clinical stage, presence of lymphatic 
invasion, ulceration, and incomplete surgical 
margins are reported as independent negative 
prognostic factors.
• Complex carcinoma and simple tubular 
carcinoma associated with prolonged survival
• Simple tubulopapillary carcinoma, intraductal 
papillary carcinoma, and malignant myoepitheli -
aloma carries 10-fold higher risk of tumor-
related death
• Adenosquamous carcinoma may have a 
high recurrence rate (50%).
• Anaplastic carcinoma and carcinosarcoma 
carry worst prognosis (<3 months) with 
>90% metastatic rate.
• Inflammatory carcinoma median survival 
time <3 months.
• WHO clinical stage may be applicable to 
noninflammatory epithelial tumors.
• Simple carcinoma and grade 1 tumors 
more commonly associated with stages I, II, 
or III.
• Lymph node invasion and less cellular 
differentiation more common in complex 
carcinoma than simple carcinoma.
• High COX2/CD31 or high COX2/VEGF 
coexpression have been associated with a 
decreased survival.
• Paraneoplastic glomerulopathy and 
• Metastasis to lymph nodes, lungs, and CNS.PREGNANCY/FERTILITY/BREEDING
• T reatment with progestin increases the 
chance of tumor development at a younger 
age.
• T reatment with progestin increases risk of 
development of benign tumor.
• T reatment with progestin and estrogen 
increases risk of malignant tumor development.
• 5-FU = fluorouracil.
• IGF-1 = insulin-like growth factor-1.
drug.
• WHO = World Health Organization.
Henry, CJ. Mammary tumors. In: Henry CJ, 
Higginbotham ML, eds., Cancer 
Management in Small Animal Practice. 
Maryland Heights, MO: Elsevier Saunders, 
2010, pp. 275–282.
Marconato L, Romanelli G, Stefanello D, 
et al. Prognostic factors for dogs with 
mammary inflammatory carcinoma: 43 
cases (2003–2008). J Am Vet Med Assoc 
2009, 235:967–972.
Rasotto R, Berlato D, Goldschmidt MH, 
Zappulli V. Prognostic significance of 
canine mammary tumor histologic 
subtypes: an observational cohort study of 
229 cases. Vet Pathol 2017, 54:571–578.
Sorenmo KU, Rasotto R, Zappulli V, 
Goldschmidt MH. Development, anatomy, 
histology, lymphatic drainage, clinical 
features, and cell differentiation markers of 
canine mammary gland neoplasms. Vet 
Pathol 2011, 48:85–97.
Sorenmo KU, Worley DR, Goldschmidt 
MH. T umors of the mammary gland. In: 
Withrow SJ, Vail DM, Page RL, eds., Small 
Animal Clinical Oncology, 5th ed. St. 
Louis, MO: Elsevier Saunders, 2013, pp. 
538–556.
T ran CM, Moore AS, Frimberger AE. 
Surgical treatment of mammary 
c arcinomas in dogs with or without 
postoperative chemotherapy. Vet Comp 
Oncol 2014, Apr 16.
available onlineMammary Gland Tumors—Dogs  (continued)

Canine and Feline, Seventh Edition  869
M BASICS
OVERVIEW
• Marijuana is a general term that typically 
refers to Cannabis sativa  or C. indica  plants 
and is synonymous with cannabis. Its legal 
status in North America has changed 
substantially in the past decade and varies 
based on the country and state. • Of the 100+ 
cannabinoids in marijuana, the primary 
psychoactive compound (i.e., induces a 
“high”) is δ-9-tetrahydrocannabinol (THC). 
THC is likely responsible for the clinical signs 
of poisoning in pets. • THC extracts can be 
added to foods or sold in a wide variety of 
products such as tinctures, capsules, oils, 
sublingual sprays, topical creams, bath bombs, 
even suppositories, or made into “concen -
trates”—wax-like formulations which are 
smoked or vaped. • The minimum lethal dose 
of marijuana plant material is greater than 3 g/
kg for dogs. • THC binds to endocannabinoid 
receptors CB1 and CB2. • Cannabidiol (CBD), 
a cannabinoid commonly used in medical 
cannabis or sold as a “supplement” for pets 
and people, is not psychoactive although, 
depending on the quality of the product, some 
may inadvertently contain THC.  
• Commonly affected organ systems are 
cardiovascular, gastrointestinal, nervous, 
ophthalmic, respiratory, renal/urologic.
Younger animals may be overrepresented due 
to an increased tendency to ingest foreign 
items.
SIGNS
• Often begin 0.5–2 hours after ingestion; 
may begin in minutes following inhalation.  
• Lethargy, ataxia, vomiting, glazed eyes, 
mydriasis, depression, hypothermia, trembling, 
urinary incontinence. • Higher doses may 
cause bradycardia, hypotension, and coma. 
Nystagmus, vocalization, sinus tachycardia, 
seizures, and hyperthermia may also occur.
• Intoxication occurs via ingestion of foods 
containing THC, medical cannabis products, 
marijuana “concentrates,” or inhalation of 
marijuana smoke. Pets in homes of recrea-
tional or medical marijuana users are at 
greater risk for exposure. • Of the cases 
reported to Pet Poison Helpline, an animal 
poison control center, about 65% involve 
food products, the majority of which also 
contain chocolate. Such foods may contain 
other toxic ingredients such as raisins, 
macadamia nuts, xylitol, etc. • Regions with 
marijuana dispensaries correlate to increased 
exposures. DIAGNOSIS
• Other illicit drugs—LSD (lysergic acid 
diethylamide), PCP (phencyclidine), 
hallucinogenic mushrooms. • Opioids 
(greater cardiac/respiratory depression, miosis, 
reversed with naloxone), benzodiazepines, 
muscle relaxants, ethanol, ethylene glycol 
(metabolic acidosis, crystalluria), methanol, 
diethylene glycol, propylene glycol, 
t ranquilizers, depressants, xylitol 
(hypoglycemia).
No specific abnormalities but should be used 
to rule out other causes.
• Human urine drug tests are generally 
unreliable and may result in false negatives. A 
positive result can typically be considered a 
true positive. • Serum, stomach contents and/
or urine can be submitted to diagnostic labs 
for confirmatory testing.
IMAGING
No specific abnormalities but abdominal 
radiography is useful if an obstruction is 
suspected (e.g., ingestion of a baggie containing 
marijuana, packaging of a food product).
 TREATMENT
• Mildly affected patients may not require 
intervention and can be kept in a low-stimu-
latory, protective environment. • T reatment is 
focused on decontamination and supportive 
care. Induce emesis following recent (<2 
hours) ingestion in asymptomatic patients if 
they have not already vomited. If sympto-
matic, gastric lavage should be considered for 
large ingestions or if concentrated products 
were ingested. • Activated charcoal q8h for 
2–3 doses if severe signs.  
• Warming/cooling measures as needed. • IV 
fluid support if poor perfusion parameters or 
dehydration. • Oxygen if respiratory 
depression. • Provide ocular lubricant and 
rotation to comatose animals.
• Antiemetics (e.g., maropitant 1 mg/kg SQ, 
IV q24h dogs or cats) as needed. • Diazepam 
(0.5–1 mg/kg IV PRN dogs or cats) or 
butorphanol (0.1–0.4 mg/kg IM or IV dogs or 
cats) for CNS stimulation, anxiety, agitation.CONTRAINDICATIONS/POSSIBLE 
hypotension. • Use phenobarbital cautiously 
due to the risk of severe sedation and 
respiratory depression.
 FOLLOW-UP
Monitor temperature, pulse, and respiration 
q2–3h until normal. Monitor blood pressure 
in severe cases (hypotension).
• Educate pet owners about the risks of 
leaving cannabis products, especially food, 
accessible to pets. Stress that pets will readily 
consume such products. • Keep pets confined 
during parties.
• Clinical signs may last up to 24 hours in 
mild cases and may be monitored at home.  
• Clinical signs may persist for several days in 
severe cases, especially if a large dose were 
ingested. • The prognosis is excellent with 
appropriate care. • Death is rare but has been 
reported in dogs ingesting foods made with 
marijuana butter.
• CBD = cannabidiol.
• THC = δ-9-tetrahydrocannabinol.
Brutlag, A., Hommerding, H. Toxicology of 
marijuana, synthetic cannabinoids, and 
cannabidiol in dogs and cats. Vet Clin Small 
Anim 2018, 48:1087–1102.
available onlineMarijuana Toxicosis

M
870  Blackwell’s Five-Minute Veterinary Consult  
M BASICS
OVERVIEW
• Urine marking—depositing of urine on 
vertical (spraying) or horizontal (especially 
novel) surfaces for communication (territo-
rial, sexual, or agonistic situations).
• Roaming—escape or wandering for the 
purpose of seeking mates, defining territory, 
obtaining food, or sensory stimulation/
• Urine marking and roaming behavior are 
normal but undesirable behaviors in 
companion cats.
• Mounting—mating behavior; mounting of 
inanimate objects for the purpose of 
masturbation.
• Common in intact males, especially if 
estrus females are present.
• Can also occur in intact females or neutered 
individuals; marking reported in 10% of 
neutered males and 5% of spayed females.
• Roaming and mounting may be seen in 
5–10% of neutered males.
• No age or breed predilection for marking or 
roaming.
• Mounting may be more common in 
sexually deprived, intact male cats mounting 
other males, females, kittens, people, and 
inanimate objects.
SIGNS
• Urine marking—characterized by the cat 
backing up to vertical object with an erect 
and quivering tail and projecting a stream of 
urine backward; may also occur with the cat 
assuming a squatting posture and depositing 
urine on horizontal surfaces, notably personal 
or novel items in the environment; urine 
deposited on multiple surface types in 
conjunction with normal litter box use for 
toileting of urine and feces.
• Mounting—of other cats, people, or 
objects.
• Urine marking may function to delineate 
territory, aggressive intent, or reproductive 
communication between cats or as a response 
to anxiety.
• Likelihood of urine marking increases with 
density of cats in the household; however, 
urine marking may occur in households with 
only 1 or 2 cats.
• Marking associated with social conflict 
between cats in the same household, introduc -
tion of new cats, new furniture, or novel objects.
• Roaming is a normal exploratory behavior 
for enrichment, food, or sexual activity.• Roaming is more likely in outdoor cats 
being housed indoors, intact male cats, and 
cats with a barren indoor environment 
(resulting in increased motivation to explore 
outdoors).
• Mounting can be seen in deprived males or 
isolated males or if males are housed in pairs.
 DIAGNOSIS
• Rule out causes of lower urinary tract 
disease and systemic diseases that might 
increase irritability including hyper- 
• Urine marking must be distinguished 
from inappropriate urination for the 
purpose of emptying the bladder. The latter 
problem is characterized by elimination on 
a consistent surface or location, may involve 
feces, and is usually associated with a 
decrease in use or avoidance of the litter box 
use. Cats that urine mark continue to use 
the litter box for toileting of urine and 
feces.
• Roaming behavior may occur due to any 
disease process that might cause a cat to seek 
isolation due to illness.
• For marking and mounting also 
consider neonatal testosterone exposure, 
treatment with anabolic steroids or 
testosterone, or retained or residual 
• Rarely do cats with roaming or mounting 
behaviors display abnormalities in lab work.
• CBC/biochemistry tests and thyroid 
evaluation can provide helpful information 
to rule out coexisting conditions and 
provide baseline data prior to initiating 
• Urinalysis required to rule out underlying 
urinary tract disorders.
• Unless indicated from baseline data, no 
further lab tests are necessary.
• In neutered and spayed females, rule out 
potential hormonal effects from retained or 
residual testicular tissue which might be 
associated with secondary sexual characteristics 
such as penile barbs and elevated testosterone 
in males or estrus-like behaviors in females.
IMAGING
Radiographs and ultrasound if exam, signs, 
and/or laboratory results indicate a need to 
further explore the urinary tract.
None indicated. TREATMENT
Marking
• Neuter and spay intact animals.
• Provide alternate marking options such as 
scratching posts and facial marking combs 
(Cat-A-Comb). For some cats the use of a 
urine marking station (empty litter box 
placed vertically at location where marking 
occurs) may be appropriate.
• Multiple resources including feeding 
stations, water bowls, climbing and perching 
stations, and litter boxes in multiple 
locations (one litter box per cat plus one 
additional).
• Manage litter hygiene so that boxes are 
scooped daily and completely cleaned weekly 
(clay litters) or monthly (clumping litters) 
using hot water only (no cleansers).
• Increase perching and hiding opportunities 
(especially elevated locations) in each room of 
the home.
• Prevent access or supervise access to area 
being marked.
• Make marked areas less appealing by using 
double-sided tape or bubble wrap, or 
unpleasant odors (e.g., mothballs).
• Manage stress factors in the household 
(address relationship issues between cats in 
the home, provide for each cat’s behavioral 
needs, manage interactions between cats and 
people in home to increase positive relation-
ships by encouraging play and reinforcement-
based training).
• Reduce exposure to outdoor cats by 
blocking visual access; decrease number of 
cats in yard (use of fencing, motion-activated 
sprinkler, remove bird feeders, etc.).
• Consider increasing (or decreasing) time 
allowed outdoors.
• Use synthetic facial pheromone (F3 
fraction) spray or diffuser.
• Consider cat-appeasing pheromone for 
intraspecific social conflict.
• If necessary, reduce numbers of cats in the 
household to reduce density if intraspecific 
conflict due to overcrowding or social 
incompatibilities are an issue.
Roaming
• Neuter if intact.
• Use double barriers at exits (for example, 
screen doors) or confine away from doors 
(e.g., room).
• Alternately, allow controlled access to 
outdoors using cat fencing or screened areas 
or outdoor access on a leash and harness.
• Enrich environment with multiple small meals, 
random treats, and increased play opportunities. 
Feed the cat as soon as it returns home.Marking, Roaming, and Mounting Behavior—Cats

Canine and Feline, Seventh Edition  871
MM• Remove outdoor reinforcements such as 
outdoor cats through the use of fencing, 
motion-activated water sprinklers, removing bird 
feeders, and insuring neighbors not feeding.
• ID cat (tags, tattoo, or microchips).
• Synthetic facial pheromone (F3) diffuser in 
home.
Mounting
• Interrupt the behavior and redirect to more 
desirable behaviors such as play.
• Identify and remove any triggers which 
initiate the behavior.
• Provide alternative outlets for play/
Marking
(SSRIs)—fluoxetine or paroxetine 0.25–1.0 mg/
kg PO q24h; side effects include sedation, 
anorexia, irritability, urine retention, constipation.
• T ricyclic antidepressants (TCAs)—clomi-
pramine 0.25–1.0 mg/kg PO q24h; side 
effects include sedation, anticholinergic 
effects, arrhythmias, and gastrointestinal 
anxiety—pheromones; l-theanine alone or in 
combination products; alpha-casozepine 
alone or in stress/calming diets (e.g., with 
l-tryptophan).
Roaming
No medications are recommended for 
roaming behavior.Mounting
• Medications might be a consideration if a 
stress/anxiety component identified.
• Fluoxetine or clomipramine as in urine 
marking.
• Lorazepam 0.125–0.5 mg per cat PO 
q12–24h; side effects include sedation, 
hyperphagia, and rare hepatic toxicity (as 
reported with diazepam).
• Do not use fluoxetine or clomipramine 
with monoamine oxidase (MAO) inhibitors 
such as selegiline.
• Caution in using TCAs when treating cats with 
diabetes, glaucoma, cardiac disease, or seizures.
• Do not combine a TCA with an SSRI or 
other drugs that might increase serotonin.
 FOLLOW-UP
• Telephone follow-up within 2 weeks after 
consultation, repeat as needed to monitor 
progress and assess response to treatment.
• ECG if concerns about cardiac status.
• CBC and biochemistry profile 3–4 weeks 
after initiating medical therapy and then 
q6–12 months.
• Response to therapy within 4 weeks.
• Continue drug therapy for minimum 8 
weeks if response noted; continue 1 month 
beyond resolution.
• When behavior is stable, wean dose by 25% 
per week.
• If behavior recurs, reinstitute lowest 
effective dose.• Some cats may need to be maintained on 
medication indefinitely.
SEE ALSO
Housesoiling—Cats.
Hart BL, Cliff KD, Tynes VV, et al. Control 
of urine marking by use of long-term 
treatment with fluoxetine or clomipramine 
in cats. J Am Vet Med Assoc 2005, 
226:378–382.
Horwitz D, ed. Blackwell’s Five-Minute 
Hoboken, NJ: John Wiley & Sons, 2018, 
pp. 700–711.
Pryor PA, Hart BL, Bain MJ, et al. Causes of 
urine marking in cats and the effects of 
environmental management on the 
frequency of marking. J Am Vet Med Assoc 
2001, 219:1709–1713.
Author  John J. Ciribassi
Consulting Editor  Gary M. Landsberg(continued)  Marking, Roaming, and Mounting Behavior—Cats

M872  Blackwell’s Five-Minute Veterinary Consult  
MMarking, Roaming, and Mounting Behavior—Dogs
  BASICS
• Marking, roaming, and mounting fall 
within the normal behavioral repertoire for 
the dog. However, they are objectionable to 
owners if shown to excess or in an inapprop­
riate context, particularly in a sexually altered 
dog. • Normal behaviors with multiple 
causes—may be maladaptive owing to stimuli 
in the environment. • Marking—generates a 
signal for conspecifics with a visual mark, 
scent (urine, feces, anal sacs, or sebaceous 
glands) or both on an object or to define 
territory. • Roaming—wandering from 
territory for exploration or in search of 
mates, food, or social contact. • Mounting—
primarily a component of mating behavior 
but also shown in social contexts and play 
(especially in prepubertal dogs).
GENETICS
None; however, may be more common in 
familial lines.
• Mounting—approximately 11%; running 
away—approximately 11%. • Marking—
unknown; estimates up to 8% .
Any breed.
• Age at onset—sexual maturity (between 6 
and 18 months of age). • Mounting may 
occur in prepubertal puppies.
• Most common in intact males. • May be 
seen in intact females in estrus, castrated 
males, and spayed females.
SIGNS
• Marking—deposition of urine and/or 
feces in locations unacceptable to owners; 
occurs inside and outside of the home. 
• Roaming—wandering behavior that takes 
the dog away from its home territory. 
• Mounting—a behavior in which a dog 
places the cranial part of its body onto other 
dogs, animals, people, or objects while 
wrapping forelimbs around the target often 
with pelvic thrusting.
• Typically unremarkable unless a medical 
etiology is suspected (especially for marking 
behavior). • For inappropriate mounting of 
other dogs, it is advisable to also perform a 
physical examination on the target animal.CAUSES
• Normal behaviors. Urine marking occurs 
most commonly in novel areas. Female dogs 
rarely mark in the home. • Hormonally 
regulated; intact males likely to roam, mark, 
and mount; prenatal testosterone surge leads 
to the brain’s response to testosterone at 
puberty (i.e., sexual dimorphic behavior). 
• Learned components possible; reproductive 
status not sole variable.
Roaming
• Anxiety. • Curiosity. • Reproduction. 
• Social contact and play.
Marking
• Medical. • Communication with conspecifics; 
communicates social rank, sexual status, 
territorial boundaries, or general information 
not related to the need to empty the bladder or 
bowel. • Anxiety if excessive or in the home.
Mounting
• Sexual (including courtship and masturbation). 
• Play. • Social status or cohesion. • Attention ­
seeking. • Anxiety. • Displacement behavior/
compulsive disorder.
• Intact males more likely to roam, mark, and 
mount. • Marking on walks; learned 
behavior. • Mounting only in front of 
owners; attention ­seeking. • Intact bitches, or 
females spayed after first heat.
  DIAGNOSIS
Normal or a sign of another diagnosis.
Roaming
• Sexually motivated. • Testosterone ­
producing tumors. • Searching for food. 
• Separation anxiety—escape/avoidance. 
• Noise phobias—escape/avoidance. 
• Territorial behavior. • Social seeking. 
• Social conflict in home territory. 
• Predatory behavior. • Escaping from 
enclosure—play/investigative behavior.
Marking
producing tumors. • Territorial behavior. 
• Social status behavior. • Conflict behavior. 
• Anxiety. • Cognitive dysfunction syndrome. 
• Housesoiling. • Excitement/submissive 
urination. • Urinary tract disease. • Any 
medical condition that causes polyuria/
polydipsia (PU/PD). • Constipation or 
diarrhea. • Anal sac disease.
Mounting
producing tumors. • Social status behavior. 
• Endocrine disease. • Urinary tract disease. • If target is another dog, look at target for: 
◦ Estrogen ­producing tumors. ◦ Infections 
of anal sacs, uterus, vagina, or urinary tract.
• If indicated, based on physical exam, 
clinical signs, sex, and age. • Thyroid testing 
if roaming for food. • In neutered males 
showing intact male behavior, consider 
baseline testosterone then administer 
gonadotropin ­releasing hormone (GnRH) 
followed by a post ­injection blood sample to 
rule out retained testicular tissue. • Urine 
culture and sensitivity. • Vaginal cytology to 
determine estrus status. • If target of 
mounting is another dog, exam target for: 
◦ Blood estrogen levels (reproductive 
tumors). ◦ Urine culture and sensitivity. 
◦ Vaginal cytology, culture and sensitivity.
• Behavioral history and clinical signs. • Rule 
out medical differentials.
  TREATMENT
ACTIVITY
DIET
No special dietary considerations.
Roaming
• Secure enclosure to prevent escape. • Leash 
walk. • Adequate exercise, attention, super­
vision, stimulation. • Doggie daycare.
Marking
• Restrict access to targeted areas with 
confinement training or barricades. • Provide 
indoor supervision when the owner is present. 
• Remove stimuli or triggers. • Express anal 
sacs if necessary. • Use Bellyband (male) or 
Puppy Pants (female). • Clean marked areas 
with effective enzymatic cleaners. • Cue/
reward ­based interaction with dog. • Avoid 
confrontation or punishment. • Counter ­
conditioning and desensitization to trigger 
stimuli or for anxiety conditions.
Mounting
• Obedience training. • Cue/reward ­based 
interaction with dog. • Counter ­conditioning 
or systematic desensitization to trigger stimuli 
or for anxiety conditions. • Adequate exercise, 
attention, and stimulation. • Ignore behavior 
if attention seeking ­ reorient or redirect into 
alternative desirable. • Avoid confrontation 
that adds to anxiety and conflict.
• Neuter intact males. • Remove retained 
testicular tissue if indicated. • Spay marking 
females.

Canine and Feline, Seventh Edition  873
MM  MEDICATIONS
• Medication is not necessary for roaming 
unless the primary problem (separation 
anxiety or noise phobias) warrants its use. 
Medical etiologies should be treated 
accordingly. • No drug is approved for the 
treatment of marking or mounting; 
medication use is only indicated if anxiety is a 
contributing motivation. • Medication 
should only be used in combination with a 
sound behavior modification plan.
• Amitriptyline 2–4 mg/kg PO q12h. 
• Clomipramine 1–3 mg/kg PO q12h. • Side 
effects, cardiac conduction disturbances, and 
gastrointestinal (GI) signs.
(SSRIs)
• Fluoxetine 0.5–2 mg/kg PO q24h. 
• Paroxetine 1–2 mg/kg PO q24h. 
• Sertraline 1–3 mg/kg PO q24h or divided 
q12h. • Side effects include inappetence, 
lethargy, irritability, urine retention and 
anticholinergic effects with paroxetine.
Azapirone
• Buspirone 0.5–2 mg/kg PO q8–12h.
• Side effects—GI signs.
In dogs with concurrent anxiety diagnoses—
alprazolam 0.01–0.1 mg/kg PO q8–12h.
TCAs are contraindicated in animals with 
• Clients should be advised that occasional 
cases of increased aggression have been 
reported with TCAs and SSRIs. • Use caution 
with all drugs if dog has hepatic or renal 
compromise. • Use benzodiazepines with 
caution in aggressive dogs because of 
potential for disinhibition.
together. • Do not use TCAs or SSRIs with 
monoamine oxidase inhibitors, including 
amitraz products and selegiline.ALTERNATIVE DRUG(S)
• For anxiety, consider dog ­appeasing 
pheromones and natural supplements 
containing alpha ­casozepine (Zylkene) alone or 
in a diet in combination with l­tryptophan 
(Canine Calm diet); l­theanine alone 
(Anxitane) or in combination products 
amurense  and Magnolia officinalis  (Solliquin); 
Souroubea  and Plantanus  (Zentrol) or probiotics 
(Calming Care). • In intact males, when the 
behavior is suspected to be hormonally 
modulated, consider the use of medications 
that decrease blood testosterone levels.
GnRH Agonists
• Do not use in breeding animals during the 
breeding season. • Effect is reversible when 
GnRH agonist is discontinued.
Megestrol Acetate
• Outdated treatment. • Side effects include 
obesity, pyometra, PU/PD, diabetes mellitus, 
mammary hyperplasia, and carcinoma.
  FOLLOW-UP
Follow ­up is variable depending on the 
severity of the problem and whether 
medication is prescribed. Help may be needed 
implementing changes to the environment 
and behavior modification. Owners should be 
encouraged to keep logs or journals detailing 
episodes of marking, roaming, or mounting 
to assess treatment success or nonresponse. If 
medication is prescribed, follow ­up and 
journals are essential to assess response. In 
urine marking, owners should be encouraged 
to supervise the dog indoors and to inspect 
areas daily for urine marks.
• Neutering males and spaying females 
reduces likelihood of marking, roaming, and 
mounting behavior. • Provide client education 
for prevention and management with proper 
husbandry and reward ­based training.
• Roaming—becoming lost or picked up by 
animal control; possible injury from car 
accidents or fighting with other animals. 
• Marking—property damage when it occurs inside the home. • Mounting—disruption of 
relationship with familiar dogs; possible fighting 
with other animals. • Pet relinquishment.
• Prognosis is good if the correct cause is 
determined and the owner is compliant with 
the behavior protocols. • Castration will 
decrease house marking by 90% or better in 
40% of male dogs, while 80% of dogs will 
decrease marking by at least 50%. Castration 
has little to no effect on urine marking in 
outdoor areas. • Castration decreases 
mounting in more than 65% of dogs but 
relatively few stop completely. Castration has 
its greatest effect when the target of mounting 
is human rather than dog.
Intact animals older than sexual maturity.
Roaming exposes pet to other animals, 
including wildlife—rabies exposure possible.
Listed medications should be avoided in 
SEE ALSO
Housesoiling—Dogs.
• GnRH = gonadotropin ­releasing hormone.
Connolly PB. Reproductive behavior 
problems. In: Horwitz DF , Mills DS, Heath 
S, eds., BSAVA Manual of Canine and 
Feline Behavioural Medicine. Gloucester: 
British Small Animal Veterinary 
Association, 2002, pp. 128–143.
pp. 690–699, 795–804, 847–853.
Author  Gerrard Flannigan
Consulting Editor  Gary M. Landsberg(continued)  Marking, Roaming, and Mounting Behavior—Dogs

M874  Blackwell’s Five-Minute Veterinary Consult  
MMast Cell Tumors
  BASICS
• Malignant round cells derived of hemato­
poietic origin containing granules packed 
with many vasoactive substances, including 
histamine, heparin, serotonin, dopamine, 
tryptase, and chymase. • T umors may affect 
dermis, subcutis, spleen, liver, intestines as 
well as other connective and mucosal sites.
• Histamine release from mast cell tumors 
(MCTs) affects a multitude of tissues. 
• Histamine (H2) receptors are primarily 
located within the stomach and histamine is 
thought to be one of the most significant 
stimulants of gastric acid secretion in addition 
to gastrin and acetylcholine. • In extreme 
cases, perforation of the gastrointestinal (GI) 
tract may occur, leading to peritonitis. 
• Histamine release around a tumor leads to 
the production of wheals, hives, and erythema 
(Darier’s flare). • Local release of heparin is 
also common, resulting in bleeding and 
subsequent bruising, which can be seen 
around the tumor.
• Skin—MCTs are the most common 
malignant cutaneous tumor of the dog. 
• GI—on necropsy evaluation, 35–83% of 
dogs with MCTs have evidence of GI 
ulceration. • Hemic/lymph/immune—
regional lymph node metastasis is common in 
high­grade tumors. • Hepatobiliary—liver 
and spleen are common distant sites of 
metastasis for high ­grade MCTs.
GENETICS
The specific breed predilections indicate that 
a genetic predisposition exists.
• Most common malignant skin tumor in the 
dog, representing approximately 7–21% of all 
canine skin tumors. • Primary visceral and 
intestinal MCTs are rare in the dog (small/toy 
breeds affected). • Second most common 
malignant skin tumor in the cat, accounting 
for 20% of cutaneous tumors. • Most 
common splenic tumors of cats, comprising 
half of the MCTs diagnosed in cats.
Species
• Dogs—brachycephalic breeds, as well as 
golden retriever, Labrador retriever, Rhodesian 
ridgeback, beagle, Staffordshire terrier, 
Weimaraner, shar ­pei, and Australian cattle 
dog. • Cats—Siamese.Mean Age and Range
• Dogs—middle ­aged, range 4 months–18 
years. • Cats—middle ­aged (8–9 for cutaneous 
mastocytic types) and older cats (intestinal and 
splenic); however, the histiocytic form of 
cutaneous MCTs affects young cats (Siamese) 
with a mean age of 2.4 years.
Dogs—no predilection; cats—male Siamese.
SIGNS
Dogs
• Mass is found in the subcutis or on the skin 
and may also be present within lipomas. 
• Regional edema or a Darier’s sign may be 
seen in the region around a tumor that has 
degranulated. • Lymphadenopathy of regional 
lymph nodes may be seen in dogs with meta  static 
disease. • History of intermittent progression 
and regression in size. • Systemic illness with 
advanced local or systemic disease; vomiting, 
anorexia, weight loss, and melena.
Cats
• Visceral disease manifests as chronic weight 
loss, anorexia, diarrhea, and lethargy. • Focal 
mass lesion may be palpated with primary 
intestinal MCT. • Cutaneous masses tend to 
be epidermal and on the face or feet.
CAUSES
• Up to 30% of canine MCTs have been 
shown to contain a mutation in the c ­kit 
oncogene, leading to constitutively activated 
receptor and unchecked cell division. • Up to 
56% of feline MCTs have a c ­kit mutation 
though these mutations do not appear to have 
any bearing on prognosis.
See Breed Predilections and Causes.
  DIAGNOSIS
• Cutaneous/subcutaneous forms—adenexal 
tumors, basal cell tumors, histiocytoma, 
lipoma, and soft tissue sarcoma. • Visceral 
forms—lymphoma, histiocytic tumors, 
malignant fibrous histiocytomas, multiple 
myeloma, hemangiosarcoma, hemangioma, 
and erythroid myeloid hyperplasia. 
• Intestinal forms—lymphoma, adeno­
carcinoma, leiomyoma, leiomyosarcoma, GI 
stromal tumors, and fungal infections.
• Anemia (initially regenerative secondary to 
GI blood loss, but can progress to microcytic, 
hypochromic, nonregenerative anemia). 
• Eosinophilia. • Identification of circulating 
mast cells is more common in the cat with 
visceral MCT than the dog. • Increased BUN 
secondary to GI bleeding.OTHER LABORATORY TESTS
• Regional lymph node aspiration and 
cytology. • Liver and splenic aspiration and 
cytology. • MCT prognostic panel. • c­kit 
PCR and immunohistochemistry staining.
IMAGING
Abdominal ultrasound—viscera assessment 
with emphasis on liver, spleen, and mesenteric 
• Fine­needle aspirate and cytology for 
definitive diagnosis. • Biopsy (incisional or 
excisional) for definitive diagnosis and 
histologic grading.
Dogs
• T wo tiered grading system for cutaneous 
MCTs: ◦ Low grade—mitotic index of <7, 
<3 multinucleated cells per 10 HPFs, <3 
bizarre nuclei per 10 HPFs, mild to moderate 
karyomegaly. ◦ High grade—mitotic index of 
at least 7, 3 or more multinucleated cells per 
10 HPFs, 3 or more bizarre nuclei per 10 
HPFs, significant karyomegaly. • No validated 
grading system for subcutaneous MCTs 
currently exist. • Intestinal MCTs tend to be 
high grade in the dog.
Cats
• Histologic forms of cutaneous MCTs: 
◦ Mastocytic form—single tumor and is the 
most common (compact or diffuse). ◦ There 
are two histologic varieties of mastocytic 
MCTs in the cat: compact—more benign 
behavior; diffuse—more undifferentiated and 
aggressive. • Histiocytic form—multiple 
lesions on the head and neck with relatively 
benign behavior.
  TREATMENT
ACTIVITY
Limit for animals with heavy tumor burdens 
(such as cats with visceral MCTs or dogs with 
large tumors) until the mass has been treated 
DIET
N/A
Owners of dogs with MCTs should be 
informed that 14–17% of dogs will develop 
additional MCTs.
• Conventional recommendations (dogs)—
2–3 cm margins and one fascial plane deep, 
may be unnecessary with low ­grade MCTs in 
dogs as many of “dirty” margins fail to locally 
regrow. • Narrow margins (cats)—majority of 
tumors will not regrow following narrow

Canine and Feline, Seventh Edition  875
MMsurgical margins. • Splenectomy (cats)—
recommended in cats with massive visceral 
tumor burden despite the presence of 
• For incompletely excised MCTs in locations 
that are not amenable to surgical re ­excision 
or in cases where another surgery is not 
possible (dogs). • T reatment of regional 
lymph node beds for high ­grade tumors 
• Can be used in a gross disease setting, but 
severe systemic degranulation reactions 
(including death) are possible. Pretreatment 
with ancillary medications is indicated.
Dogs
• Vinblastine 2–3 mg/m2 IV q7 days for 4 
treatments, then q14 days for 4 treatments 
and prednisone 1 mg/kg PO q24h. 
• Vinblastine only 3.5 mg/m2 IV q14 days. 
• Lomustine 50–70 mg/m2 PO q21 days. 
• Toceranib phosphate (Palladia) 2.75 mg/kg 
PO Monday, Wednesday, Friday.
Cats
• Lomustine 32–60 mg/m2 PO q4–6 weeks. 
• Vinblastine 2 mg/m2 IV q7 days for 4 
and prednisone 1 mg/kg PO q24h.
CONTRAINDICATIONS 
AND PRECAUTIONS
• Vinblastine—use with caution in animals 
with liver disease; drug is also myelo­
suppressive and possesses vesicant properties. 
• Lomustine is hepatotoxic and should be 
avoided in dogs with underlying liver disease; 
• drug is extremely myelosuppressive and 
associated with refractory thrombocytopenia. 
Administer with Denamarin. Unknown time 
to white blood cell nadir in cats. • Toceranib 
can cause GI ulcers, myelosuppression, muscle 
pain, hypertension, proteinuria and GI upset.
• Toceranib should be used with caution with 
other drugs that induce gastric ulcers such as 
prednisone or nonsteroidal anti ­inflammatory 
drugs (NSAIDs), or in patients with gastric 
ulceration secondary to MCT. • Lomustine 
should be used with caution with other 
hepatotoxic drugs such as NSAIDs.ALTERNATIVE DRUG(S)
Symptomatic treatment—diphenhydramine, 
prednisone famotidine or other H2 
inhibitors, omeprazole, and sucralfate should 
be considered for any dog or cat with gross 
mast cell disease and clinical symptoms 
consistent with GI bleeding.
  FOLLOW-UP
Dogs
• Low­grade cutaneous—complete surgical 
resection should be curative in the majority of 
patients. Median survival time greater than 2 
years. Follow ­up should include evaluation 
every 3 months for 1 year with physical 
examination and lymph node assessment. 
• High ­grade—complete surgical resection 
evaluate every 3 months for 1.5 years with 
physical examination, blood work, abdominal 
ultrasound, and lymph node assessment then 
every 6 months for another 1.5 years.
Cats
Visceral or intestinal—abdominal ultrasound 
and blood work every 3 months for 1 year.
N/A
Chemotherapy ­related myelotoxicity or 
• Complete excision of low ­grade MCTs in 
most locations is curative. • Complete 
excision of high ­grade MCTs even with 
aggressive treatment is associated with 
eventual tumor progression/relapse. 
• Incomplete excision of a low ­grade MCT 
may require additional local therapy with 
another surgery (often cured) or radiation 
therapy (93% disease ­free at 3 years). 
• Incomplete excision of a high ­grade MCT 
requires additional local therapy in addition 
to systemic chemotherapy. • Regional 
metastasis to a lymph node should be treated 
with surgical excision at the time of the 
primary tumor removal. Systemic chemo­
therapy is necessary. • Evidence of distant 
metastasis is often treated with systemic 
chemotherapy or ancillary therapies alone 
with a median survival of 4 months or less.  MISCELLANEOUS
Progressive and metastatic disease has the 
potential to cause excessive parietal cell 
production of hydrochloric acid with 
associated gastric ulceration, melena, and 
iron­deficiency anemia and gastric 
perforation.
N/A
N/A
While on chemotherapy dogs should not be 
bred. There are no long ­term studies 
regarding fertility in dogs or cats previously 
treated with lomustine, vinblastine, or 
receptor tyrosine kinase inhibitors (RTKIs).
SYNONYMS
• Mastocytoma. • Systemic mastocytosis.
• MCT = mast cell tumor.
drug.
• RTKI = receptor tyrosine kinase inhibitor.
www.merckvetmanual.com/mvm/index
Kiupel M, Webster JD, Bailey KL, et al. 
Proposal of a 2 ­tier histologic grading 
system for canine cutaneous mast cell 
tumors to more accurately predict biological 
behavior. Vet Pathol 2011, 48(1):147–155.
London CA, Kisseberth WC, Galli SJ, et al. 
Expression of stem cell factor receptor 
(c­kit) by the malignant mast cells from 
spontaneous canine mast cell tumours. J 
Comp Pathol 1996, 115(4):399–414.
Wilcock BP , Yager JA, Zink MC.The 
morphology and behavior of feline 
cutaneous mastocytomas. Vet Pathol 1986, 
23(3):320–324.
Author  Heather M. Wilson ­Robles
available online(continued)  Mast Cell Tumors

876  Blackwell’s Five-Minute Veterinary Consult  
MMastitis
  BASICS
OVERVIEW
• Bacterial infection of one or more lactating 
• Result of ascending infection, trauma to the 
gland, or hematogenous spread.
• Escherichia coli , staphylococci, and β-hemolytic 
streptococci most commonly involved; 
Mycobacterium  and blastomycosis reported.
• Potentially life-threatening infection; may 
lead to sepsis if systemic involvement.
• Postpartum bitch and queen.
• Pseudopregnant lactating bitch or queen 
(rare).
SIGNS
• Neglect of puppies or kittens.
• Failure of puppies or kittens to thrive.
• Firm, swollen, warm, and painful 
mammary gland(s) from which purulent or 
hemorrhagic fluid can be expressed.
• Fever, dehydration, and shock—with 
systemic involvement.
• Abscessation or gangrene of gland(s) can 
result.
• Ascending infection via teat canals.
• T rauma inflicted by puppy or kitten 
toenails and teeth.
• Poor hygiene.
• Systemic infection originating elsewhere 
(e.g., metritis).
• Rarely secondary to fibroadenomatous 
hyperplasia in queens.
  DIAGNOSIS
• Galactostasis—no systemic illness; cytologic 
examination and culture of milk aid 
differentiation.
• Inflammatory mammary adenocarcinoma—  
affected gland does not produce milk; 
differentiated by biopsy.
• Leukocytosis with left shift, or leukopenia 
with sepsis.
• Hemoconcentration (increased packed cell 
volume, total plasma protein concentration), and 
azotemia from dehydration or prerenal effects.OTHER LABORATORY TESTS
N/A
IMAGING
Ultrasonography reveals loss of distinct 
layering of normal tissue in glands, decreased 
echogenicity, increased heterogeneity, and 
altered blood vessel density on color Doppler.
• Cytology—neutrophils, macrophages, and 
other mononuclear cells can be observed in 
normal milk; the presence of large numbers 
of free and phagocytosed bacteria and 
degenerative neutrophils occurs with mastitis.
• Microbial culture—identification and 
sensitivity of microorganisms from milk of 
affected glands; screening for methicillin-
resistant Staphylococcus aureus  recommended.
  TREATMENT
• Inpatient until stable.
• Puppies and kittens—neonates may be 
allowed to continue nursing unless glands are 
necrotic or dam is systemically ill; affects 
choice of antibiotics; monitor weight gain in 
neonates: pups should gain 10% of birth 
weight per day, kittens should gain a 
minimum of 7–10 g/day.
• IV isotonic crystalloid fluid to treat 
dehydration, hypovolemia, shock.
• Correct electrolyte imbalances, hypo -
volemia, hypoglycemia.
• Apply warm compress and milk out 
affected gland(s) several times daily.
• Cover friable glands to prevent excoriation 
if nursing is allowed.
• Application of cabbage leaf wraps to 
affected glands may speed resolution.
• Abscessed or gangrenous glands—require 
surgical debridement.
• Open wound management or negative 
pressure wound therapy may be needed after 
surgery in some cases; negative pressure 
therapy may also be used for conservatively 
managed cases.
• Acidic milk—weak bases; erythromycin 
10 mg/kg PO q8h, lincomycin 15 mg/kg PO 
q8h, or trimethoprim-sulfadiazine 15–30 mg/
kg PO q12h for 21 days.
• Alkaline milk—weak acids; amoxicillin or 
cephalosporin 20 mg/kg PO q8h, dogs and cats; 
amoxicillin/clavulanic acid 13.75 mg/kg PO q12h 
(dogs); 62.5 mg/cat PO q12h (cats) for 21 days.• Either alkaline or acidic milk—
chloramphenicol 40–50 mg/kg PO q8h 
or enrofloxacin 5–20 mg/kg/day PO for 
21 days.
• May infuse affected gland(s) with 1% 
betadine solution by lacrimal cannula.
• Cabergoline 5 μg/kg PO q24h for 5–7 days 
to suppress lactation in unaffected glands in 
patients with sepsis; neonates must be 
hand-reared.
Patient allowed to nurse—avoid tetracycline 
and chloramphenicol; may use cephalo -
sporins, amoxicillin, and amoxicillin with 
clavulanic acid. Enrofloxacin may be used in 
dogs up to 3 weeks of age.
  FOLLOW-UP
• Physical examination and CBC.
• Repeated ultrasonographic evaluation helps 
assess healing—normal distinct layering of 
tissues will appear with recovery.
 PREVENTION/AVOIDANCE
• Clean environment.
• Hair shaved from around mammary glands.
• Toenails of puppies and kittens clipped.
• Ensure neonates nurse from all glands.
• Probiotic administration.
• Abscessation or gangrene—may cause loss 
of gland(s).
• Hand-raising puppies and kittens—requires 
considerable commitment by the owner; may 
affect behavioral outcome of offspring.
Prognosis—good with treatment.
Periparturient disorders in the bitch. In: 
Johnston SD, Root Kustritz MV, Olson PNS, 
eds., Canine and Feline Theriogenology. 
pp. 131–134.
Author  Tessa Fiamengo
acknowledge the prior contribution of Joni L. 
Freshman.

Canine and Feline, Seventh Edition  877
MMaternal Behavior Problems
  BASICS
Abnormal maternal behavior is either excessive 
maternal behavior in the absence of neonates 
or deficient maternal behavior in the presence 
of the dam’s own neonates. The latter is more 
common in dogs, the former in cats.
The pathophysiology of one type of excessive 
maternal behavior, pseudocyesis, appears to 
be elevated progesterone levels following 
estrus in unbred bitches followed by an 
abrupt drop in progesterone levels. The 
pathophysiology of the refusal to accept 
puppies by females after caesarean section is 
the waning of factors, including oxytocin, 
needed during the sensitive period for 
acceptance of the neonate. The pathophysiology 
of other types of deficient maternal behavior 
is unknown. The impairment or absence of 
mother–infant bonding strongly affects the 
offspring’s sociability or affiliative behavior 
throughout the animal’s lifespan.
• Behavioral. •  Reproductive.
GENETICS
There is no identified genetic predisposition, 
but a breed disposition for deficient maternal 
behavior in Jack Russell terriers indicates 
there may be a genetic component. There are 
genetic models in mice. The genes responsible 
for deficient maternal behavior in mice are 
paternally imprinted. If this is true in dogs 
and cats, one would expect that rejecting 
mothers were normally mothered themselves, 
but their paternal grandmother may have 
been deficient.
The incidence of deficient maternal behavior 
has not been determined but seems to be low, 
less than 1% of cases in a behavior practice. 
Pseudopregnancy is more common. Cannibalism 
of offspring is more common in cats and may 
account for approximately 12.5% of all kitten 
deaths.
Species
Poor maternal behavior may be more 
common in Jack Russell terriers and cocker 
spaniels, but there has been no quantitative 
study.
Primiparous females and older bitches seem 
to be at risk of deficient maternal behavior. 
Lower ranking females that have not bred successfully have a higher likelihood of 
entering pseudocyesis, which may allow for 
them to help raise the offspring.
Female generally, but some males may allow 
suckling behavior.
SIGNS
Deficient Maternal Behavior
Absent maternal behavior; the mother simply 
abandons her offspring. This is most apt to 
occur after caesarean section.
Poor Maternal Behavior
• The mother stays with her offspring but 
will not allow them to nurse. •  The mother 
may show inadequate retrieval of young, 
insufficient cleaning of the young, or failure 
to stimulate elimination. •  The bitch carries 
the puppies from place to place without 
settling down. •  In the most extreme form, 
the mother kills some or all of her litter.
Abnormal Maternal Behavior
• The bitch or queen may allow her 
offspring to suckle but kills her offspring 
either at birth or over a period of days. 
Occasionally the bitch, or more rarely the 
queen, will abandon or attack her offspring 
if it has changed in odor or appearance. A 
female may be disturbed by another animal 
or by people and can redirect her aggression 
to her offspring. •  Cannibalism of kittens 
may occur as a result of too large a litter or 
overcrowding. •  A bitch may accidentally 
disembowel or even consume offspring 
completely while eating the fetal membranes 
and umbilical cord. This should be distin­
guished from normal licking, which can 
be quite vigorous, even dislodging the pup 
from a teat.
Cats with kittens may be aggressive to other 
animals, especially dogs in the same house­
hold. Bitches may be aggressive to unfamiliar 
humans or even to familiar humans, 
especially if they are hypocalcemic or painful 
(i.e., mastitis).
Excessive Maternal Behavior
• The pseudopregnant bitch or a bitch spayed 
during the late luteal phase of the estrous 
cycle adopts, attempts to nurse, and guards 
inanimate objects (stuffed animals or even 
leashes). The pseudopregnant bitch may have 
mammary development and may lactate. 
• The newly spayed queen may steal kittens 
from a lactating queen. Queens post ­spaying 
may also lactate if suckled.
CAUSES
• Genetics—offspring of poor mothers. 
• Sick/unhealthy offspring. •  Environmental 
(see Risk Factors).RISK FACTORS
• The presence of kittens in the environment 
of the recently spayed cat may prompt 
excessive maternal behavior and kitten 
stealing. •  The risk of excessive carrying of 
pups, redirected aggression, or even 
cannibalism is increased if there are other 
dogs or too many people present in the nest 
area. •  Primiparous females or those 
subjected to caesarian section are at higher 
risk than multiparous or naturally delivering 
females. •  A large litter of kittens or sick 
offspring. •  Queens fed low protein diets 
during late gestation and lactation may show 
decreased mother–kitten social interactions 
and retarded attachment formation. •  Other 
risk factors include individual differences, 
lack of experience, pain, discomfort, and 
suboptimal conditions. •  Inability to perform 
species ­specific behavior before, during, and 
after parturition increases the possibility of 
infanticide or ingestion of offspring.
  DIAGNOSIS
• The most important differential is between 
primary abnormal maternal behavior and 
poor maternal behavior secondary to mastitis 
or metritis. •  Lactation tetany can result in 
aggressive behavior, although this behavior is 
rarely directed at the puppies and occurs later 
in lactation, not at parturition.
Usually normal unless other medical 
conditions are present. Blood calcium levels 
will be low if the bitch is suffering from 
lactation tetany.
Only as indicated by metabolic conditions of 
the bitch or queen.
Presence of milk in the mammary glands of 
females with excessive maternal behavior.
  TREATMENT
Normal health care.
DIET
• Adequate diet for nursing bitches and 
queens to meet protein, energy and calcium 
demands. •  Restricted diets for pseudocyesis 
to discourage lactation and diminish milk 
production. •  In the case of deficient 
maternal behavior, the bitch or queen should 
be fed ad libitum to encourage lactation.

878  Blackwell’s Five-Minute Veterinary Consult  
MCLIENT EDUCATION
Abnormal or Poor Maternal Behavior
• The bitch that is carrying her pups or 
exhibiting redirected aggression to them 
should be isolated in a quiet, dark area. The 
bitch that bites her pups should be muzzled 
and mildly sedated. The owner must stimulate 
elimination of the puppies or kittens because 
the muzzled female cannot. An Elizabethan 
collar inhibits cannibalism in queens. •  The 
bitch should be attended at parturition and 
the pups removed temporarily if she is biting 
the pups themselves in addition to the 
umbilical cord. •  Bitches and queens with 
poor maternal behavior may exhibit the same 
behavior with subsequent litters. •  Some 
mothers reject specific offspring that are cold 
or inactive, which indicates a problem with 
the individual offspring and warrants 
veterinary intervention. •  If the mother rejects 
the entire litter, abnormality is with the dam.
• Cats that have stolen kittens should be 
separated from the biologic mother and 
kittens. •  The mothered objects should be 
removed from the pseudopregnant bitch. 
However, some bitches will compulsively 
search for the object or transfer maternal 
behavior to another. In which case, it is in the 
bitch’s best interest to allow her to remain 
with the object. •  Food intake should be 
restricted to inhibit lactation.
Maternal Aggression toward Animals or 
Humans
The best treatment for maternal aggression 
beyond weaning is to separate the kittens; 
weaning alone may not suffice because the 
presence of the kittens alone may sustain or 
even reinstate maternal aggression in a queen 
separated from her kittens for several weeks.
• Delay spaying for 4 months post estrus to 
avoid post ­spaying maternal behavior and its 
accompanying aggression. •  Spaying avoids 
future excessive maternal behavior in the 
absence of young.
• Mibolerone was the drug of choice for 
pseudopregnant bitches or those exhibiting 
maternal behavior and lactation following 
spaying. The dose is 16 μg/kg PO once daily 
for 5 days. Mibolerone is a potent anabolic–
androgenic steroid which inhibits prolactin 
and thereby inhibits lactation. The drug is no 
longer available except through some 
compounding pharmacies. •  Bromocriptine (Parlodel) can be used to inhibit prolactin. 
The dose is 10 μg/kg for 10 days. Should not 
be administered to pregnant animals. 
• Cabergoline is a dopamine agonist shown 
to be effective for the treatment of pseudo­
pregnancy in dogs by lowering prolactin. 
Dosage is 5 μg/kg PO q24h for 4–6 days. 
Some animals may require more than one 
course of treatment. Not commercially 
available in North America.
• Oxytocin may be administered either 
parenterally 1–5 units or by nasal spray 
(Syntocinon). •  Because prolactin appears to 
be necessary for maternal behavior in other 
species, a dopamine blocker, acepromazine 
(0.55–2.2 mg/kg PO), can be used. 
Dopamine inhibits prolactin release.
• Do not use mibolerone in cats because it 
has a narrow margin of safety in that species. 
It should not be administered to Bedlington 
terriers due to their predisposition for chronic 
hepatitis. •  Do not give oxytocin to pregnant 
animals or in combination with sympatho­
mimetic agents.
Mibolerone can cause masculinization that 
may include male sexual behavior, clitoral 
hypertrophy, vulvovaginitis, and urinary 
incontinence in females. Bromocriptine can 
cause gastrointestinal vomiting, sedation, and 
hypotension as well as abortion.
• If tranquilizers are administered, care must 
be taken that the puppies or kittens are not 
sedated. •  Do not use estrogen or progester­
ones at the same time as mibolerone.
  FOLLOW-UP
Puppies or kittens of females with deficient or 
poor maternal behavior should be monitored 
daily to ensure they are gaining weight.
• Place a nursing female in quiet, comfortable 
quarters away from noise and disturbance by 
other animals or people. •  Do not rebreed 
females with poor maternal behavior. 
Determine whether any female offspring of 
the female with abnormal behavior have also 
exhibited poor maternal behavior. In other 
species, poor maternal behavior is a paternally 
imprinted gene; the father must contribute 
the gene for poor maternal behavior. The 
daughters of rejecting mothers will not reject, 
but the daughters of their sons may. •  Allow 
after parturition.POSSIBLE COMPLICATIONS
• Loss of offspring. •  Hand ­reared puppies 
and kittens frequently have abnormal or 
deficient social behavior. This is due in part 
to insufficient suckling time and to the 
consequences of lack of maternal licking, 
which adversely affects response to stress and 
reproductive behavior. •  Absent maternal 
environment during the first 8 weeks has 
been associated with increased anxiety and 
aggression in puppies.
• Excessive maternal behavior usually wanes 
around the time of normal weaning (6–8 
weeks). •  Poor and deficient maternal 
behavior can occur with each litter. 
• Maternal aggression by the bitch may begin 
as early as nest building behavior, reaches its 
height during the first 2 weeks after 
parturition and may last for 3 weeks post 
parturition. •  Kittens from queens with poor 
maternal behavior can be cross ­fostered to 
another lactating queen. Puppies may also be 
cross­fostered to another lactating bitch, but 
this is best accomplished within the first week 
of life. Best success of cross ­fostering occurs 
between related dams.
Poor maternal behavior is more likely in very 
young and very old mothers.
• Consider especially drug use and effect of 
disease on the fetus. •  Do not breed dogs 
with history of poor maternal behavior.
SYNONYMS
Mismothering
Connolly PB. Reproductive behaviour 
problems. In: Horwitz D, Mills D, Heath S, 
eds., BSAVA Manual of Canine and Feline 
Behavioural Medicine. Gloucestershire, UK: 
BSAVA, 2002, pp. 128–143.
Houpt KA. Maternal behavior. In: Domestic 
Animal Behavior, 5th ed. Ames, IA: 
Wiley ­Blackwell, 2011, pp 235–270.
Root Kustritz MV. Reproductive behavior of 
small animals. Theriogenology 2005, 64(3): 
734–746.
Authors  Amy L. Pike and Amy Learn
Katherine A. Houpt. 
available onlineMaternal Behavior Problems  (continued)

Canine and Feline, Seventh Edition  879
MMaxillary and Mandibular Fractures
  BASICS
Fractures of the mandibles, maxillae, and 
associated structures are described according 
to location, severity (i.e., tooth involvement, 
soft tissue tears, and type of bone fracture), 
and effects of the muscles of mastication on 
reduction.
Effects of the Muscles of Mastication
The muscles that open and close the mouth 
may help reduce (favorable) or displace 
(nonfavorable) a fracture.
Classification of Jaw Fracture by 
Location
• Rostral mandible—including the canines 
and incisors. • Mandibular horizontal ramus. 
• Mandibular vertical ramus. 
• Temporomandibular joint. • Rostral 
maxillary/incisive bone. • Maxillary/facial 
fractures. • Maxillary symphysis. 
• Combination fractures.
Species
SIGNS
• Vary greatly according to the location, type, 
extent, cause, and underlying risk factors 
resulting in the injury. • Facial deformity, 
malocclusion, fractured teeth, oral or nasal 
bleeding, and inability to properly close the 
jaw are common signs.
CAUSES
Injury, trauma, and predisposing factors.
• High-risk environment or temperament. 
• Oral infections (e.g., periodontal 
disease, osteomyelitis), neoplasia, or 
certain metabolic diseases (e.g., hypopara -
thyroidism)—may result in weaker jaws that 
are more prone to injury. • T raumatic injury 
affecting the jaws or teeth. • Congenital or 
hereditary factors resulting in weakened or 
deformed jaw bone.
  DIAGNOSIS
A thorough and complete physical exam -
ination is very important in traumatic jaw 
injuries as many unseen or multiple injuries 
and complications are possible.
• Temporomandibular joint (TMJ) 
conditions—see Temporomandibular Joint 
Disorders. • Tooth subluxation or luxation 
(i.e., interference with jaw closure). • Endodontic disease (e.g., tooth abscess). 
• Foreign body lodged in or near the oral 
cavity. • Maxillary or mandibular nerve 
injury or disease. • Masticatory muscle 
myositis. • Craniomandibular osteopathy. 
As required—to assess and treat shock from 
initial injury; to assess animal prior to surgery.
IMAGING
Radiography—intraoral and extraoral; CT 
and MRI.
• Oral examination. • Neurologic examination. 
• Biopsy for histopathology, if indicated. 
• Bacterial culture and sensitivity, if indicated.
• Non-unions. • Neoplasia. • Osteomyelitis. 
• Periodontal and/or endodontic disease.
  TREATMENT
Typical Types of Treatments for Classes 
of Fractures
• Interarch stabilization (caudal fractures or 
severely comminuted combination fractures 
including the TMJ)—tape muzzle; maxillo-
mandibular fixation (MMF) with dental 
composites or acrylic materials; cross-arch 
wiring or buttons (maxilla to mandible). 
• Intra-arch stabilization (symphyseal and 
parasymphyseal injuries)—pin and wire 
combination, dental wiring, acrylic or 
composite splint. • Intraoral stabilization 
with splint (mandibular body fractures, useful 
in edentulous patients)—composite or acrylic 
splint. • Intraoral stabilization with wire 
(mandibular body, maxillary fractures)—
interdental wiring (Ivy loop, Stout’s multiple 
loop, Essig and Risdon techniques); dental 
wiring: circumdental for splint anchorage (pig 
tails, cerclage or twists); osseous wiring 
(circumferential, transosseous, transcircumfer -
ential). • Internal fixation (most types of 
fractures, used selectively with consideration 
of teeth and roots): orthopedic wire; 
mini-plates; screws; intramedullary pins ( not 
within the mandibular canal). • External 
fixation (most types of fractures, used 
selectively with consideration of teeth and 
roots)—intramedullary pins with bars 
(stainless steel or carbon) or tubing (e.g., 
Penrose) reinforced with composite or acrylic. 
• Salvage surgery (fractures with large defects, 
non-unions)—condylectomy (nonrepairable 
fractures of the TMJ); cheiloplasty (salvage 
procedure to maintain reasonable mandibular 
support in certain nonunion conditions); 
rostral (or other) mandibulectomy (used in certain non-union cases or with massive 
injury).
Initial Treatment
• Awareness of occlusion, tooth roots, and 
anatomy during treatment is critical. • Patient 
should be intubated, pharyngostomy or 
transmylohyoid placement aids in occlusal 
checks intraoperatively. • Teeth in the 
fracture line should be assessed and main-
tained by appropriate treatment until the 
fracture heals, if possible, as removal may 
result in instability. • Bone graft to reestablish 
structural stability—autograft (harvested from 
individual); allograft (same species); alloplast 
(artificial material). • T reatment with 
composite/acrylic splints in association with 
wiring (Ivy loop, Stout’s multiple loop) is 
generally very effective. • Assess soft tissue 
damage; debride and suture where 
appropriate.
Procedure
• Disinfect with dilute chlorhexidine and 
clean and polish teeth (flour pumice without 
fluoride). • Reduce fracture in proper 
occlusion. • Before applying splint materials, 
coat adjacent teeth and soft tissue with 
petroleum jelly. Acid etch the teeth with a 
37% phosphoric acid gel; leave on for 30–60 
seconds; rinse off thoroughly and air dry the 
teeth. Spot bonding of the teeth with light- 
cured unfilled resin if desired to increase 
adherence of dental materials to teeth.
Materials
Acrylics
• Warning: Use acrylics in well-ventiliated 
areas. They also generate heat can result in 
thermal injury to the teeth. • Place the 
powder and liquid in a salt-and-pepper 
fashion in small increments (to avoid 
hyperthermic reaction) until the desired shape 
and density of splint attained. • Finish and 
smooth with acrylic bur on high-speed 
handpiece.
Composites (Protemp Garant, Maxitemp)
• Little exothermal reaction and fumes; more 
expensive. • After acid-etching, use a dentinal 
bonding agent and apply a separator agent to 
opposing arcade to prevent composite from 
bonding to these teeth during occlusion 
check. • With a new mixing tip, apply 
product to splint area, shaping it as it 
hardens. • Finish and smooth with white 
stone bur and place a final layer of unfilled 
resin.
Circumferential Osseous Wiring or 
Suturing
• Wiring around the bone—used most 
commonly for symphyseal separations. 
• 20- or 18-gauge needle—to pass wire. 
• 24- to 28-gauge wire—in neonates, small 
dogs or cats, absorbable (long-acting, e.g., 
PDS) or nonabsorbable 1- to 2-0 suture

880  Blackwell’s Five-Minute Veterinary Consult  
Mmaterial can sometimes be substituted for 
wire. • Run wire from stab incision (ventral 
intermandibular space) to vestibule; pass 
behind canines, down through vestibule on 
opposite side, and back down through the 
ventral incision. • Tighten wire to reduce 
fracture, but do not overtighten the wire ends 
or the teeth may be pulled too far medially 
(lingually displaced) and hit the palate. If this 
happens, either loosen the wire ends or place 
a figure-eight wire looped around the canine 
teeth and under the jaw.
Homecare
• Orthodontic wax—soft, pliable wax sent 
with owner to periodically cover irritating 
wires, or can cover wire twists and ends with 
dental composite materials. • Oral 
irrigants—use twice daily for oral hygiene 
and to reduce bacteria; chlorhexidine 
solutions help reduce bacteria; zinc and 
ascorbic acid solutions (Maxi-Guard Gel) 
help reduce bacteria and stimulate soft 
tissue healing. • Diet—soft food or gruel 
may be required during healing. 
• Nutritional and fluid maintenance 
required. • Chewing exercise—avoid hard 
chew items during healing process.
• Based on type of fracture, available 
equipment, supplies, and the doctor’s 
knowledge, experience, and comfort level. 
• T reatment selection is based on four major 
points: (1) Reduction of fracture and 
reasonable contact of fracture ends, if 
possible. (2) Reestablishment of natural 
occlusion, and avoidance of causing a 
malocclusion when the fracture is reduced. 
(3) Stabilization sufficient for proper healing. 
(4) Salvage condition (nonrepairable or 
nonstabilizable condition).
• Local anesthesia—intraoral local blocks; 
regional nerve blocks: mental n., mandibular n., 
infraorbital n., and maxillary n. • Injectables—
hydromorphone, buprenorphine, fentanyl, CRI, certain drug combinations. • T ransdermal 
patches—fentanyl. • Oral—nonsteroidal 
anti-inflammatory drugs (NSAIDs); gabapen -
tin, tramadol, hydrocodone.
Limit usage to cases with suspected osteo -
myelitis; bacterial culture and sensitivity should 
be performed to prescribe appropriate drug.
  FOLLOW-UP
• Physical—recheck every 2 weeks post -
operatively until appliance is removed. 
• Radiographic—recheck 4–6 weeks postop -
eratively, then every 2 weeks until fracture is 
healed and/or appliance is removed. • Fracture 
site may temporarily (1–2 weeks) be more at 
risk to refracture after the support of the 
appliance is removed. • Once the fracture line 
is stable, compromised teeth may need 
additional endodontic treatment (e.g., root 
canal) or careful extraction. • If the healing 
process results in a malocclusion—orthodon -
tics, endodontics, and/or selective exodontia 
(extraction) may be required. • Other 
considerations—stability of fracture and 
appliance; oral hygiene; oral intake of food and 
water; maintenance of weight; appropriate 
urination and defecation; indications of pain or 
swelling.
T ry to minimize risk of trauma.
• Malocclusion. • Endodontic disease. 
• Osteomyelitis. • Non-union. 
• Sequestrum. • Dehiscence. • Neurologic 
defects. • Facial pain syndrome. 
• Impaired mastication. • Temporary 
weight loss. • Soft tissue trauma due to 
appliance or wires.
Possible Sequelae
Impaired Mastication
• TMJ arthritis—chronic or intermittent 
TMJ pain; may require condylectomy. 
• Malocclusion—dental attrition; may 
require extractions. • Non-union—may 
require partial or complete mandibulectomy 
or maxillectomy. • Ankylosis or pseudoankylosis of the mandible at the TMJ 
or zygomatic arch region.
Facial Pain Syndrome
• Acute or chronic. • Due to nerve trauma 
from injury or as a complication of surgery.
Nerve Damage
Affecting motor function
• Generally good; however, predisposing 
factors, initiating force, location, type of 
fracture, quality of homecare, and selection of 
treatment modality all affect the healing 
outcome. • 4–12 weeks to bony union.
• Malocclusion. • Mastication difficulty. 
• Lack of head symmetry. • Soft tissue 
trauma. • Periodontal disease. • Chipped, 
broken, luxated, or avulsed teeth.
Fracture healing may be faster in younger 
animals.
SEE ALSO
Temporomandibular Joint Disorders.
• MMF = maxillomandibular fixation.
drug.
https://avdc.org/avdc-nomenclature/
Taney K, Smithson CW. Oral surgery—
fracture and trauma repair. In: Lobprise 
HB, Dodd JR, eds., Wigg’s Veterinary 
Hoboken, NJ: John Wiley & Sons, 2019, 
pp. 265–288.
Author  Kendall Taney
available onlineMaxillary and Mandibular Fractures  (continued)

Canine and Feline, Seventh Edition  881
MMegacolon
  BASICS
A disorder characterized by persistent, 
irreversible dilation of the colon that is often 
the result of chronic constipation/obstipation.
• Idiopathic dilated megacolon is the most 
common cause of chronic constipation in cats 
and occurs due to generalized colonic smooth 
muscle dysfunction. • The diagnosis of idio- 
 pathic dilated megacolon is often preceded by 
chronic, recurrent constipation so it is unclear 
whether a primary disorder of colonic smooth 
muscle occurs first or whether smooth muscle 
dysfunction results from prolonged colonic 
distension. • Megacolon can also occur 
secondary to abnormal neurologic function of 
the colon, including dysautonomia, spinal cord 
injury or deformities, pelvic nerve injury, and 
autonomic ganglioneuritis. • Colonic agangli -
onosis/hypoganglionosis (Hirschsprung’s disease 
in humans) is a congenital absence of ganglia in 
the colonic smooth muscle; affected segments 
are unable to relax, resulting in megacolon. 
• Hypertrophic megacolon can develop as a 
consequence of obstructive lesions and will 
progress to dilated megacolon if the obstruction 
is not corrected.
• Gastrointestinal. • Neuromuscular—  
concurrent neurologic abnormalities may be 
seen when megacolon has a neurogenic cause. 
• Musculoskeletal—megacolon can occur 
secondary to pelvic fractures. • Endocrine/
metabolic—megacolon can result in electro -
lyte derangements due to prolonged vomiting. 
Electrolyte and endocrine abnormalities 
(hypercalcemia, hypokalemia, hypothyroidism) 
can promote constipation and possibly lead to 
or exacerbate megacolon.
GENETICS
N/A
Unknown
N/A
Species
Cat > dog.
Possible increased risk in Manx cat.
• Idiopathic megacolon—young adult cats 
most commonly (mean 6 years) although cats 
of any age can be affected. • Acquired 
megacolon—none.
MaleSIGNS
• Idiopathic megacolon—typically a chronic/
recurrent problem; signs often present for 
months to years. • Acquired megacolon—signs 
may be acute or chronic. • Constipation/  
obstipation. • Tenesmus with small or no fecal 
volume. • Hard, dry feces. • Infrequent 
defecation. • Small amount of diarrhea (often 
mucoid) may occur after prolonged tenesmus. 
• Occasional vomiting, anorexia, and/or 
lethargy with chronic fecal impaction. 
• Abdominal palpation reveals an enlarged 
colon with hard feces. • Digital rectal 
examination may indicate an underlying 
(obstructive) cause and confirms fecal 
impaction. • Dehydration. • Unkempt hair 
coat. • Weight loss with chronicity. 
• Neurologic examination may reveal 
underlying neurologic disease.
CAUSES
• Mechanical obstruction—pelvic fractures, 
neoplasia, rectal foreign body, rectal stricture, 
atresia ani, prostatomegaly. • Neurologic 
disease—dysautonomia, sacral spinal cord 
deformities (Manx cat), cauda equina 
syndrome, pelvic nerve injury or dysfunc -
tion. • Endocrine/metabolic—hypercalce -
mia, hypokalemia, hypothyroidism, severe 
dehydration. • Drugs—opioids, antichol -
inergics, phenothiazines.
• Chronic constipation. • Conditions leading 
to obstruction or difficulty defecating, 
including prior trauma and spinal cord injury 
or deformity. • Possible association with low 
physical activity and obesity as well as 
consumption of bone meal in dogs.
  DIAGNOSIS
• Other causes of palpable colonic masses (e.g., 
lymphoma, carcinoma, intussusception)—
distinguish on the basis of texture, rectal 
examination, imaging, and mucosal biopsy. 
• Dysuria/stranguria—exclude by palpation of 
the bladder and colon, and by urinalysis. 
• Tenesmus due to inflammation of the colonic 
mucosa (colitis)—exclude by palpation, rectal 
examination, and colonoscopy with mucosal 
biopsy.
• Often normal. • May show evidence of 
dehydration and stress leukogram. • Electrolyte 
abnormalities may develop; may be prerenal 
azotemia with dehydration. • Urinalysis—  
typically unremarkable.OTHER LABORATORY TESTS
Total thyroxine (T4) to assess thyroid function.
IMAGING
• Abdominal/pelvic radiographs to identify 
underlying causes. • Can easily visualize an 
enlarged, fecal-filled colon on survey abdominal 
radiographs. • Abdominal ultrasound may 
identify mural or obstructive masses.
Rarely need colonoscopy to rule out mural or 
intraluminal obstructive lesions.
• Feline idiopathic megacolon has no defining 
histologic changes. Smooth muscle typically 
appears normal with evidence of normal 
innervation. Mucosal and submucosal 
ulceration, fibrosis, and inflammation can be 
variably present and are secondary to chronic 
fecal impaction. • Megacolon resulting from 
other etiologies may have features such as 
abnormalities in or reduced numbers of ganglia 
(ganglioneuritis or hypogangliosis), or smooth 
muscle hypertrophy (hypertrophic megacolon).
  TREATMENT
• If administration of laxatives or enemas fails to 
resolve fecal impaction, inpatient management 
and manual evacuation of feces will be necessary. 
• For manual evacuation of feces, the patient 
should be placed under general anesthesia and 
intubated to prevent aspiration should 
manipulation of the colon trigger vomiting or 
regurgitation: ◦ Warm water combined with a 
water-based lubricant can be administered 
during the procedure to help facilitate removal of 
feces. Feces are then removed manually while 
providing gentle assistance with abdominal 
palpation of the colon. ◦ Periprocedural 
administration of an IV antibiotic with a good 
anaerobic spectrum can be considered in case 
manipulation of the compromised colon results 
in bacterial translocation. ◦ This procedure may 
need to be repeated if the impaction is too severe 
to safely accomplish removal of all feces under 
one anesthetic event. • T rickle administration of 
polyethylene glycol 3350 via nasogastric tube for 
24–48 hours prior to manual extraction will 
result in better fecal hydration and may facilitate 
stool removal.
• Most patients require parenteral fluid support 
to correct dehydration. • IV administration of 
balanced electrolyte solutions is the preferred 
route. • Control nausea and vomiting with 
antiemetic medications.
ACTIVITY
• Encourage activity and exercise. 
• Restriction indicated postoperatively if 
surgery is performed.

882  Blackwell’s Five-Minute Veterinary Consult  
MDIET
• Many patients require a low-residue 
producing diet; bulk-forming fiber diets can 
worsen or lead to recurrence of colonic fecal 
distension. • A soluble fiber-rich diet may be 
helpful. • A maintenance-type diet can be 
supplemented with fiber-enriched foods 
(pumpkin) or products containing 
fermentable fiber such as Metamucil.
• Following treatment for constipation, medical 
therapy, including dietary management, 
laxatives, and/or colonic prokinetics, may be 
required long term and has the potential to fail. 
• Subtotal colectomy is indicated in cases of 
medical treatment failure.
• An underlying obstructive cause should be 
surgically corrected, if possible. Alternatively, 
subtotal colectomy has been described in the 
successful management of megacolon occurring 
secondary to pelvic fracture malunion. • For 
patients that do not respond favorably to 
medical treatment, subtotal colectomy is the 
treatment of choice. • Subtotal colectomy may 
be required with obstructive megacolon even if 
the obstruction is corrected if irreversible 
changes in colonic motility have already 
occurred. • Avoid enema administration or 
attempts at colonic evacuation prior to surgery. 
These efforts result in increased likelihood of 
fecal contamination of the abdomen during 
surgery. • Subtotal colectomy can be performed 
with either ileorectal or colorectal anastomosis. 
Preservation of the ileocolic junction is 
recommended as this results in more formed 
stool compared to cats in which it is excised.
• Colonic prokinetic agents—cisapride (5-HT 
receptor agonist) has been shown to stimulate 
colonic smooth muscle motility in cats and dogs 
with constipation. The dose is 0.1–0.5 mg/kg 
PO q8–12h, but may be increased up to 1 mg/
kg if well tolerated. Metoclopramide is not 
effective for constipation. • Hyperosmotic 
laxatives—polyethylene glycol 3350 powder 
(Miralax®) 1/8–¼ tsp with food q12h; lactulose 
0.5 mL/kg PO q8–12h to effect. In cats with 
severe constipation, polyethylene glycol 
electrolyte solution (GoLytely®, Colyte®) can be 
given via nasogastric or nasoesophageal feeding 
tube at 6–10 mL/kg/h for 12–48 hours in a 
24-hour care hospital setting to facilitate passage 
of feces, either as an alternative to or in 
preparation for manual evacuation of feces. 
• Enemas—5–10 mL/kg warm water or a 
50–50 mixture of warm water and water-soluble 
lubricant administered slowly via a lubricated 
10–12 Fr red rubber catheter gently passed into 
the rectum. Lactulose can also be administered 
as an enema at a dose of 5–10 mL/kg.CONTRAINDICATIONS
• Sodium phosphate retention enemas (e.g., 
Fleet by C.B. Fleet Co., Inc.)—because of 
their association with severe hypocalcemia. 
• Mineral oil and white petrolatum—because 
of danger of fatal lipoid aspiration pneumonia 
due to lack of taste.
Common hairball laxatives (e.g., Laxatone, 
Cat-a-Lax) are typically ineffective.
N/A
• Docusate sodium can be used as a stool 
softener in place of lactulose. • Psyllium can 
be added to food at a dose of ¼–1 tsp twice a 
day. Fiber may be beneficial in early stages 
but may exacerbate clinical signs in cats with 
loss of colonic muscle function. • Dioctyl 
sodium sulfosuccinate (Colace®) is an 
emollient laxative that can be given as an 
alternative to lactulose or polyethylene glycol. 
• Ranitidine, a member of the H2-receptor 
antagonist drug class, may stimulate colonic 
motility and can be given if cisapride is 
unavailable. The dose is 1–3 mg/kg PO q12h. 
• One recent pilot study using multistrain 
probiotic SLAB51™ showed clinical improve-
ment in some cats with chronic constipation 
and idiopathic megacolon.
  FOLLOW-UP
• Following colonic resection and anastomosis—  
for 3–5 days check for signs of dehiscence and 
peritonitis. • Clinical deterioration warrants 
abdominocentesis and/or peritoneal lavage to 
detect anastomotic leakage. • Continue fluid 
support until the patient is willing to eat and 
drink.
• Repair pelvic fractures that narrow the 
pelvic canal. • Avoid exposure to foreign 
bodies and feeding bones. • Encourage 
physical activity.
• Recurrence or persistence—most common. 
• Potential surgical complications include 
peritonitis, persistent diarrhea, fecal inconti-
nence, stricture formation, and recurrence of 
obstipation. • T raumatic perforation of the 
colon is a serious complication of overzealous 
fecal evacuation.
• Historically, medical management has been 
unrewarding for the long term. • Cisapride 
appears to improve the prognosis with 
medical management in some patients, but 
may not suffice in severe or long-standing 
cases. • Postoperative diarrhea—expected; 
typically resolves within 6 weeks (80% of cats with idiopathic megacolon undergoing 
subtotal colectomy) but can persist for several 
months; stools become more formed as the 
ileum adapts by increasing reservoir capacity 
and water absorption. • Subtotal colectomy is 
well tolerated by cats; constipation recurrence 
rates are typically low.
Perineal hernia.
Concurrent medical conditions (e.g., chronic 
renal insufficiency, hyperthyroidism) may 
occur with idiopathic megacolon, because 
many cats are old.
N/A
• The effect of cisapride on the fetus is 
unknown. • Patients would be at increased risk 
for dystocia if they carried a pregnancy to term.
SYNONYMS
None
SEE ALSO
• Constipation and Obstipation.
• Dyschezia and Hematochezia.
• Perineal Hernia.
Carr AP , Gaunt MC. Constipation resolution 
with administration of polyethylene-glycol 
solution in cats (abstract). J Vet Intern Med 
2010, 24:753.
Nemeth T, Solymosi N, Balka G. Long-term 
results of subtotal colectomy for acquired 
hypertrophic mega- colon in eight dogs. J 
Small Anim Pract 2008, 49:618–624.
Rosin E, Walshaw R, Mehlhaff C, et al. 
Subtotal colectomy for treatment of chronic 
constipation associated with idiopathic 
megacolon in cats: 38 cases (1979–1985). J 
Am Vet Med Assoc 1988, 193:850–853.
cats with chronic constipation/megacolon: a 
pilot study. Benef Microbes 2018, 
Washabau RJ. Large intestine dysmotility. In: 
Elsevier, 2013, pp. 757–764.
available onlineMegacolon  (continued)

Canine and Feline, Seventh Edition  883
MMegaesophagus
  BASICS
A focal or generalized, diffuse dilation of the 
esophagus with decreased to absent peristalsis.
• In the normal esophagus, the presence of a 
food bolus in the proximal esophagus 
stimulates afferent sensory neurons. •  Signals 
are transferred centrally, via the vagus and 
glossopharyngeal nerves to the tractus 
solitarius and nucleus ambiguus. •  Motor 
impulses travel back via the efferent neurons 
of the vagus nerve to stimulate striated muscle 
(canine) and striated and smooth muscle 
(feline) esophageal contraction. •  Lesions 
anywhere along this pathway may lead to 
megaesophagus and resultant retention of 
food and liquids. •  Approximately 60% of 
dogs with megaesophagus have an “achalasia-
like” syndrome of the lower esophageal 
sphincter (LES), that is a well-documented 
cause of megaesophagus in people. 
• Functional obstruction of the LES results 
in esophageal dilatation, retention of ingesta, 
loss of esophageal motility, and associated 
clinical signs of esophageal dysphagia. •  Dogs 
with evidence of esophageal achalasia may 
respond to targeted therapy with subsequent 
improvement in esophageal dysphagia. 
• Focal megaesophagus is typically caused by 
esophageal obstruction secondary to strictures 
or a vascular ring anomaly with dilation of 
the esophagus proximal to the obstruction.
• Gastrointestinal—dysphagia, regurgitation, 
weight loss. •  Musculoskeletal—weakness, 
weight loss, exercise intolerance, dysphonia. 
• Nervous—possible manifestation of 
systemic neurologic/neuromuscular disorder. 
• Respiratory—aspiration pneumonia, 
coughing.
GENETICS
• Congenital form—megaesophagus can be 
inherited in smooth fox terriers (autosomal 
recessive) and miniature schnauzers (autosomal 
dominant or 60% penetrance autosomal 
recessive). In addition, Jack Russell terriers, 
springer spaniels, long-haired miniature 
dachshunds, golden retrievers, Labrador 
retrievers, and Samoyeds are predisposed to 
the congenital form of myasthenia gravis. 
• Other breeds in which acquired 
megaesophagus is more commonly reported 
include German shepherd dog, Great Dane, 
Irish setter, Labrador retriever, pug, and 
Chinese Shar-Pei.
• Acquired form—many diseases, especially 
neuromuscular diseases, may have an 
association with megaesophagus. Genetic predispositions for such diseases are listed 
under each disease separately.
• Congenital forms—relatively uncommon. 
• Acquired disease—increasingly recognized 
in the dog and rare in the cat.
Species
Dogs are more commonly affected than cats.
• Dogs—see Genetics. •  Cats—Siamese and 
Siamese-related cats.
• Congenital cases present soon after birth or 
at weaning during transition from liquid diets 
to solid foods. •  Acquired cases may be seen 
at any age, depending on the etiology.
SIGNS
• Owners often report vomiting; the 
veterinarian must differentiate vomiting from 
regurgitation. •  Regurgitation (considered 
the hallmark sign); dysphagia; coughing/nasal 
discharge with aspiration pneumonia; 
ravenous appetite or inappetence; weight loss 
or poor growth; ptyalism, and halitosis. 
Dysphonia may occur secondary to neuro-
muscular disease. •  Other signs depend upon 
• Cervical swelling may be noted, representing 
a distended cervical esophagus; ptyalism; 
halitosis; increased respiratory noises, nasal 
discharge, and fever (if concurrent pneumo-
nia); cachexia; weakness; weight loss. •  Assess 
for concurrent neurologic deficits that may 
indicate generalized disease. Special attention 
should be paid to cranial nerves IX, X, and 
XI. Muscle atrophy (if present) may be focal 
or generalized.
CAUSES
Idiopathic megaesophagus; congenital 
myasthenia gravis (MG) (rare).
Acquired/Adult Onset
• Idiopathic (most common). 
• Neuromuscular disease—MG, focal or 
generalized (25% of cases in dogs); systemic 
lupus erythematosus (SLE); myositis/
myopathic disease; dysautonomia (more 
common in cats); botulism; vagal dysfunction/
damage (bilateral); a possible association 
between laryngeal paralysis and esophageal 
dysmotility secondary to polyneuropathy has 
been identified. •  Brainstem disease—disease 
involving cranial nerves IX, X nuclei or 
peripheral nerves. •  Esophageal obstruc-
tion—vascular ring anomaly; esophageal or 
periesophageal neoplasia (e.g., lymphoma, thymoma, leiomyoma); stricture; foreign 
body; granuloma. •  Toxicity—lead, thallium, 
anticholinesterase; acrylamide. •  Endocrine 
disease—hypoadrenocorticism, hypothyroid-
ism (controversial). Thymoma is associated 
with MG and megaesophagus in approxi-
mately 25% of cats. •  Miscellaneous—gastric 
dilatation volvulus, hiatal hernia, gastroe-
sophageal intussusception; esophagitis 
(gastroesophageal reflux, parasitic infection).
  DIAGNOSIS
• Must distinguish regurgitation from 
vomiting. •  Regurgitation—passive; little to 
no abdominal effort; no prodromal phase; 
regurgitated material has increased amounts 
of thick mucus. Regurgitation often occurs 
many hours after a meal has been consumed 
due to retention of the food bolus within the 
esophagus. •  Vomiting—active process; 
prodromal phase; vomited material may have 
increased bile staining. •  The shape of the 
expelled material, presence of undigested 
food, and length of time from ingestion to 
regurgitation or vomiting are less helpful to 
differentiate.
• May be unremarkable. •  Inflammatory 
leukogram may be seen with pneumonia. 
• Other changes may identify underlying 
etiology—basophilic stippling on red blood 
cells with lead toxicity; electrolyte distur-
bances with hypoadrenocorticism, although 
lack of electrolyte changes does not rule out 
hypoadrenocorticism; hypercholesterolemia 
with hypothyroidism; elevated creatine kinase 
with myopathic disease, particularly during 
the acute phase.
• Acetylcholine receptor (AchR) antibody titer 
in all cases of acquired megaesophagus (screen 
for MG). Approximately 2% of dogs with 
generalized MG are seronegative; testing 
should be repeated 2–3 months later, 
particularly if initial antibody titer is only 
slightly below the reference interval. Dogs 
with congenital MG do not have an auto -
immune disorder associated with circulating 
AchR antibodies, but instead have a deficiency 
of the AchR receptor itself. Serologic testing of 
antibodies to the AchR in puppies or dogs 
suspected of the congenital form of MG is 
thus of no diagnostic value and is a waste of 
money. •  Adrenocorticotropic hormone 
(ACTH) stimulation test or baseline cortisol 
level for hypoadrenocorticism. •  Thyroid 
panel for hypothyroidism (may be affected by 
concurrent disease). •  Blood and urine lead

884  Blackwell’s Five-Minute Veterinary Consult  
Mlevels. •  Antinuclear antibody (ANA) titers 
for SLE. •  Blood cholinesterase levels for 
organophosphate toxicity.
IMAGING
Survey Thoracic Radiographs
• Dilated esophagus filled with air, fluid, or 
food. Interpret thoracic radiographs in 
anesthetized animals and anxious or painful 
animals with caution in light of aerophagia 
that can cause distention of the esophagus 
with air. •  Evidence of aspiration pneumonia 
may be evident. •  Ventral displacement of the 
trachea on lateral radiographs. •  Ventrodorsal 
radiographs may show lateral tracheal 
displacement. •  Evidence of underlying 
etiology: mediastinal mass (thymoma), hiatal 
hernia, neoplasia, etc. •  Radiographs do not 
differentiate dogs with megaesophagus due to 
MG from dogs with megaesophagus due to 
other etiologies.
Contrast Esophagram 
and Videofluoroscopy
• Barium liquid and barium meal may 
demonstrate abnormal pooling, poor motility, 
or structural lesions. Iohexol may be used if 
perforation is a concern. •  Use with caution 
in animals with megaesophagus due to risk of 
aspiration of contrast material. •  Exercise 
extreme caution in animals with radiographic 
evidence of pneumonia. •  Monitor animals 
closely after radiographs for signs of aspiration. 
• Videofluoroscopy—may be used to assess 
primary and secondary esophageal peristalsis. 
May help determine the best food consistency 
for long-term management. Videofluoroscopy 
commonly demonstrates marked retention of 
the food bolus within the esophagus for 
hours, despite gravity-assisted feeding in a 
Bailey chair. A bird-beak effect of the lower 
esophageal sphincter may be evident due to 
esophageal achalasia.
• Esophagoscopy—may be used for foreign 
body retrieval, evaluation of suspected 
obstructive lesions, neoplasia, or esophagitis. 
Distal esophageal neoplasia or stricture of the 
lower esophageal sphincter may mimic 
idiopathic megaesophagus and may require 
endoscopy for diagnosis. •  Electrophysiology—
in cases of suspected neuromuscular disease, 
may be used in conjunction with muscle and 
nerve biopsies. •  Additional tests—may be 
indicated in cases of CNS disease: CSF 
analysis, distemper titers, brain CT or MRI. 
• Fecal exam—may indicate Spirocerca lupi  
Depend upon underlying etiology and 
presence of complicating factors.  TREATMENT
• T reat underlying etiology (when 
applicable). •  Most important aspects are 
meeting nutritional requirements and 
treating or preventing aspiration 
• Aspiration pneumonia may require oxygen 
therapy, nebulization/coupage, fluid therapy 
with balanced electrolyte solution. •  These 
animals may be recumbent and require soft 
bedding and should be maintained in sternal 
recumbency or turned to alternate down side 
every 4 hours.
ACTIVITY
Depending on etiology, restricted activity is 
not necessary.
DIET
• Calculate precise nutritional requirements, 
including degree of debilitation. 
• Experimentation with different food 
consistencies is essential (e.g., liquid gruel, 
small meatballs, blenderized slurries). 
• Many cases benefit from gastrostomy tube 
placement for feeding; however, this does 
not prevent gastroesophageal reflux and 
potential aspiration or aspiration of saliva. 
• Feeding and drinking should be from an 
elevated position (45–90° from floor) and 
the upright position should be maintained 
for 10–15 minutes after eating or drinking. 
An upright position may be easier to attain 
with the use of a specific “chair” (e.g., 
Bailey chair).
• Most cases of megaesophagus require 
life-long therapy. Even if an underlying 
etiology is found and treated, prognosis for 
resolution of idiopathic acquired megae -
sophagus is unlikely. Client dedication is 
important for long-term management. 
• Most animals succumb to or are 
euthanized because of aspiration pneumonia, 
malnutrition, or progression of underlying 
disease.
• Surgery is indicated for vascular ring 
anomalies, bronchoesophageal fistula, some 
foreign bodies and other obstructive lesions, 
or thymectomy. •  Balloon dilation is 
indicated for cases of esophageal stricture. 
• Surgical management of esophageal 
achalasia (Heller’s myotomy followed by 
fundoplication) has been well documented in 
people with acquired megaesophagus secondary to esophageal achalasia and in a 
recent publication evaluating acquired 
megaesophagus in dogs.
• Antibiotics for aspiration pneumonia 
(ideally based on culture and sensitivity from 
transtracheal wash or bronchoalveolar 
lavage). •  Therapy for underlying etiology if 
indicated—immunosuppressives (use with 
caution if pneumonia present) for immune-
mediated disease; pyridostigmine for MG, 
prednisone supplementation for hypoadreno -
corticism. •  Proton pump inhibitors (PPIs) 
are superior acid suppressants to H2-receptor 
antagonists (H2RAs) for the management of 
moderate to severe esophagitis, and are not 
susceptible to tolerance (tachyphylaxis) that 
has been well documented in people, dogs, 
and cats within 3–5 days following the 
implementation of H2RA therapy. PPIs such 
as omeprazole or pantoprazole must always 
be given twice daily for optimal benefit (1 
mg/kg PO or IV q12h). In addition, PPIs 
should be gradually tapered before discon -
tinuing to avoid acid rebound 
hypersecretion.
Prokinetics
The use of prokinetics such as cisapride and 
metoclopramide in dogs and cats with diffuse 
megaesophagus is contraindicated and should 
be avoided because they will tighten the LES 
(which already has increased tone in most 
dogs with megaesophagus as a consequence of 
achalasia) and possibly increase the risk of 
aspiration pneumonia. Prokinetics such as 
metoclopramide (1.0–2.0 mg/kg/day IV CRI 
or PO q6–8h) or cisapride (0.5 mg/kg PO 
q8–12h) are more effective for minimizing 
esophagitis in dogs that do not have mega -
esophagus. Cisapride is more potent and 
effective than metoclopramide for increasing 
LES tone and enhancing gastric emptying, 
and can be used in animals with evidence of 
esophagitis but no evidence of megaesopha-
gus, or in cats with esophageal dysmotility 
affecting the smooth muscle in the distal 1/3 
of the esophagus.
• Absorption of orally administered drugs 
may be compromised. •  Injectable forms 
should be used when applicable. 
• Immunosuppression, if indicated, must be 
used with caution due to risk of aspiration 
pneumonia.Megaesophagus  (continued)

Canine and Feline, Seventh Edition  885
M  FOLLOW-UP
• Thoracic radiographs when aspiration 
pneumonia is suspected (fever, cough, 
lethargy). •  Cases of pneumonia may require 
CBC, blood gas analysis, and bronchoalveolar 
lavage. Repeat thoracic radiographs in 
animals with congenital megaesophagus as 
spontaneous resolution may occur. •  Examine 
and weigh patients regularly to evaluate 
disease progression and ensure adequate 
nutritional intake.
If an esophageal foreign body is identified, 
remove as quickly as possible.
• Aspiration pneumonia. •  Others, 
depending on etiology.
• Congenital cases have a guarded prognosis 
(20–46% recovery). •  Miniature schnauzers 
may have better prognosis. •  Prognosis may 
be improved with identification and treatment 
of specific etiology (e.g., hypoadrenocorticism, 
vascular ring anomaly). •  Roughly 50% 
cases of MG respond to therapy; however, 
megaesophagus may persist even if other signs 
of MG resolve. •  Prognosis for idiopathic, adult-onset disease is poor. •  Owner 
dedication is crucial.
Aspiration pneumonia.
• Signs of regurgitation in very young animal 
or at weaning may indicate congenital lesion. 
• Prognosis may be better in young animals.
• None for megaesophagus. •  Rabies 
vaccination status should be determined in 
any animal with possible neurologic disease.
SYNONYMS
• Esophageal aperistalsis. •  Esophageal 
dilatation.
SEE ALSO
• AchR = acetylcholine receptor.
• ANA = antinuclear antibody.• H2RAs = H2-receptor antagonists.
• MG = myasthenia gravis.
• https://www.marvistavet.com/
megaesophagus.pml •  http://www.
baileychairs4dogs.com/
Grobman ME, Hutcheson KD, Lever TE, 
et al. Mechanical dilation, botulinum toxin 
A injection, and surgical myotomy with 
fundoplication for treatment of lower 
esophageal sphincter achalasia-like 
syndrome in dogs. J Vet Intern Med 2019, 
33(3):1423–1433.
Mace S, Shelton GD, Eddlestone S. 
Megaesophagus. Compend Contin Educ 
Vet 2012, 34(2):E1.
McBrearty AR, Ramsey IK, Courcier EA, 
et al. Clinical factors associated with death 
before discharge and overall survival time in 
dogs with generalized megaesophagus. J Am 
Vet Med Assoc 2011, 238(12):1622–1628.
Authors  Stanley L. Marks and Marguerite F . 
Knipe
available online(continued)  Megaesophagus

M886  Blackwell’s Five-Minute Veterinary Consult  
MMelanocytic Tumors, Oral
  BASICS
T umor of melanocytes arising in the oral 
cavity (gingiva, palate, tongue), most 
frequently malignant.
• Locally invasive, may invade into under­
lying bone. • Metastatic in >75% cases in 
dogs. • Immunohistochemical evaluation 
may be required for the diagnosis of 
amelanotic melanomas.
• Oral cavity (gingiva, palate, tongue). 
• Metastatic sites—regional lymph nodes and 
lungs most common; liver, spleen, bones, 
meninges, other.
GENETICS
Unknown
• Dogs—most common malignant oral tumor, 
accounting for ∼40% of oral malignancies. 
• Cats—third most common oral malignancy.
Species
Dog more than cat.
• Dogs—cocker spaniel, miniature poodle, 
retriever breed, dachshunds, chow chow 
(tongue). • Cats—no predilection 
reported.
• Dogs—11 years (5–18 years). • Cats—12 
years (11–15 years).
• Dogs—male predisposed (in some studies). 
• Cats—not reported.
SIGNS
• Excessive salivation. • Halitosis. 
• Dysphagia. • Hyporexia. • Bloody oral 
discharge. • Weight loss.
• Oral mass (up to a third are poorly 
pigmented or amelanotic), often friable and 
ulcerated. • Loose teeth if involvement of 
mandibular or maxillary bone. • Facial 
deformity (including exophthalmos). 
• Regional lymphadenomegaly. • Pain or 
Overrepresented breeds of dogs.  DIAGNOSIS
• Other oral malignancy (squamous cell 
carcinoma, fibrosarcoma). • Acanthomatous 
ameloblastoma/peripheral odontogenic 
fibroma. • Gingival hyperplasia. • Tooth root 
abscess. • Foreign body reaction.
IMAGING
• High ­detail skull radiography or dental 
radiographs—evaluate for osteolytic changes. 
• Advanced imaging (contrast ­enhanced CT 
or MRI) affords better detail and helps with 
therapeutic planning (surgery or radiation 
therapy). • Three ­view thoracic imaging 
(radiography or CT)—evaluate lungs for 
metastasis. • Abdominal imaging (ultrasono­
graphy or CT)—to complete clinical staging; 
occasional distant metastasis in abdominal 
visceral organs.
• Carefully measure primary tumor—  
important prognostic information. • Fine­
needle aspiration and cytology of ipsilateral 
and contralateral mandibular lymph nodes 
recommended to evaluate for regional 
metastases, regardless of their size and 
consistency upon palpation—up to 40% of 
normal ­sized regional lymph nodes have 
metastasis. • Carefully palpate other regional 
lymph nodes (retropharyngeal, parotid, 
superficial cervical) and perform fine ­needle 
aspiration and cytology if abnormal. • Large 
and deep ­tissue biopsies may be required to 
obtain definitive diagnosis (via histo­
pathology) and gather prognostic information. 
• Fine­needle aspiration or biopsies of 
primary tumor should always be taken from 
inside the mouth, not through the skin (could 
compromise local control with surgery due to 
needle or biopsy track seeding).
Gross
• Masses may be ulcerated and friable; often 
bleed when large and malignant. 
• Amelanotic to dark brown, gray, or black. 
• Vary greatly in size; often invasive in 
surrounding tissues.
Cytologic Findings
• Brown, rod ­like intracellular granules 
(melanin) of various size and shapes. 
• Pigment may be absent with amelanotic 
tumors. • May see melanophages (phagocytic 
macrophages) with large intracytoplasmic vacuoles containing melanin, especially in 
lymph nodes. • More cellular atypia observed 
in malignant tumors.
• Cells may vary in shape (e.g., epithelioid, 
fusiform, dendritic, and mixed), degree of 
pigmentation, and cytoplasmic morphology. 
• Malignant—generally high mitotic index; 
nuclear and nucleolar pleomorphism (more 
atypia, less differentiation); invasive into 
surrounding tissues; amelanotic may pose a 
diagnostic challenge; immunohistochemistry 
and special stains may be particularly useful; 
proliferation markers may help predict 
behavior. • Immunohistochemistry (e.g., 
Melan ­A, S100, PNL2, HMB ­45, vimentin)—
may help confirm a diagnosis, especially if 
amelanotic (approximately one ­third of cases). 
• Histopathology report should include mitotic 
index (mitoses per 10 HPF), degree of atypia/
differentiation, invasiveness, and surgical 
margins if excisional biopsy.
  TREATMENT
Inpatient if undergoing aggressive oral 
surgery.
Pain management—multimodal analgesia 
(preemptive, intra ­ and postoperative) is 
mandatory with aggressive surgeries.
ACTIVITY
Restrict until sutures are removed and all 
surgical wounds healed.
DIET
• Soft food recommended to prevent tumor 
ulceration or following aggressive oral surgery. 
• Avoid toys and hard treats until oral tissues 
are healed completely.
• Discuss importance of clinical staging. 
• Discuss need for early aggressive approach 
with surgical removal • Warn caretaker that 
malignant melanoma frequently metastasizes 
early in the course of the disease, resulting in 
a guarded prognosis. • Adjuvant therapy is 
recommended to improve survival time and 
delay metastasis. • Repeat clinical staging 
recommended after therapy.
• Goal should be to remove all macroscopic 
tumor burden and obtain complete margins 
in order to improve overall prognosis. 
• Radical en bloc  surgical excision—required 
(e.g., mandibulectomy or maxillectomy); well

Canine and Feline, Seventh Edition  887
MMtolerated by most patients; surgical margins of 
at least 2 cm; improved survival when margins 
are free of neoplastic cells. • Surgical removal 
of the draining lymph node(s) is recommended 
when metastasis confirmed or suspected and 
no evidence of distant (e.g., lung) metastatic 
disease.
• May be used to improve local disease 
control following unplanned incomplete 
resection. • As single modality treatment for 
macroscopic disease, radiation therapy affords 
a good response rate (>80%) and may offer 
long­term control with inoperable tumors; 
3–6, weekly to twice weekly, large fractions of 
megavoltage radiation therapy.
• Carboplatin has been described for oral 
melanoma in dogs and remains recommended 
following surgical excision of macroscopic 
disease (primary tumor, metastatic regional 
lymph nodes). • Carboplatin may still be 
advised if surgical excision is not possible, 
with a response rate approximating 30% on 
measurable disease, and may be coupled with 
palliative radiation therapy protocols. 
updated treatments that may be available. 
• No effective chemotherapy described in 
cats. • Pain management with multimodal 
analgesia therapy is mandatory (nonsteroidal 
anti­inflammatory drugs, opioid, adjuvant 
analgesia medications, aminobisphosphonates 
if osteolysis is present).
Immunotherapy
• Many immunotherapies have been 
attempted with varied success. • A 
therapeutic vaccine is available (Oncept™) 
that involves the injection of human cDNA 
(xenogeneic) coding for a melanocyte ­specific 
protein, tyrosinase, and results in a 
measurable immune response in some 
patients. • The tyrosinase vaccine is approved 
for the postoperative treatment of stage II and 
III oral malignant melanomas and some 
reports suggest improved survival times in 
comparison with historical control studies.
Avoid the use of cisplatin in cats.PRECAUTIONS
Seek advice from an oncologist before initiating 
drugs (myelosuppression, specific toxicities, etc.).
Drugs with overlapping toxicities should be 
avoided.
Novel therapeutics or treatment regimens may 
be available. Contact a veterinary oncologist for 
any updated treatments that may be available.
  FOLLOW-UP
• Evaluate for local recurrence and regional 
metastasis every 2–3 months following surgery 
or earlier if the owner believes the mass is 
returning; or if the patient is other  wise not 
normal. • Recommend three ­view thoracic 
radiography at the time of rechecks (every 
3 months).
• Poor wound healing, dehiscence, infection 
possible after aggressive surgery. • Early radiation 
side effects, such as mucositis or dermatitis, may 
result from hypofractionated protocols.
• Poor prognosis when untreated (median 2 
months). • Depends upon disease stage; better 
prognosis with stage I. • Complete surgical 
excision (local and regional lymph node when 
positive) is essential to improve the prognosis—
median survival time with surgery alone varies 
with stage: ◦ Stage I—over 18 months. ◦ Stage 
II and III—5–12 months. ◦ Stage IV—less 
than 3 months. • Adjuvant carboplatin chemo­
therapy is not consistently reported as beneficial 
but remains recommended. • Prognosis of 
stage II and III canine oral melanoma may be 
improved to over 18 months with the adjuvant 
use of the recombinant xenogeneic tyrosinase 
vaccine. • Survival with radiotherapy treatment 
alone (dogs)—6–10 months. • Cause of death 
in dogs may be metastatic disease or local 
tumor recurrence. • Overall prognosis in cats is 
poor; most tumors are locally invasive and 
diagnosed late in the course of the disease; 
cause of death is often due to local disease 
progression—median survival time of 146 days 
in 5 cats treated with hypofractionated 
radiation therapy.  MISCELLANEOUS
Older age at diagnosis (>12 years) might 
predict a poorer prognosis in dogs.
SEE ALSO
Melanocytic T umors, Skin and Digit.
Boston SE, Lu X, Culp WT, et al. Efficacy of 
adjuvant therapies administered to dogs 
after excision of oral malignant melanomas: 
151 cases (2001–2012). J Am Vet Med 
Assoc 2014, 245:401–407.
Brockley LK, Cooper MA, Bennett PF . 
Malignant melanoma in 63 dogs (2001–
2011): the effect of carboplatin chemotherapy 
on survival. N Z Vet J 2013, 61:25–31.
Farrelly J, Denman DL, Hohenhaus AE, et al. 
Hypofractionated radiation therapy of oral 
melanoma in five cats. Vet Radiol 
Ultrasound 2004, 45:91–93.
Grosenbaugh DA, Leard AT, Bergman PJ, 
et al. Safety and efficacy of a xenogeneic 
DNA vaccine encoding for human 
tyrosinase as adjunctive treatment for oral 
malignant melanoma in dogs following 
surgical excision of the primary tumor. Am 
J Vet Res 2011, 72:1631–1638.
Proulx DR, Ruslander DM, Dodge RK, et al. 
A retrospective analysis of 140 dogs with 
oral melanoma treated with external beam 
radiation. Vet Radiol Ultrasound 2003, 
44:352–359.
Rassnick KM, Ruslander DM, Cotter SM, 
et al. Use of carboplatin for treatment of 
dogs with malignant melanoma: 27 cases 
(1989–2000). J Am Vet Med Assoc 2001, 
218:1444–1448.
Smedley RC, Spangler WL, Esplin DG, et al. 
Prognostic markers for canine melanocytic 
neoplasms: a comparative review of the 
literature and goals for future investigation. 
Vet Pathol 2011, 48:54–72.
Verganti S, Berlato D, Blackwood L, et al. 
Use of Oncept melanoma vaccine in 69 
canine oral malignant melanoma in the UK. 
J Small Anim Pract 2017, 58:10–16.
Louis ­Philippe de Lorimier.(continued)  Melanocytic Tumors, Oral

888  Blackwell’s Five-Minute Veterinary Consult  
MMelanocytic Tumors, Skin and Digit
  BASICS
OVERVIEW
• Benign or malignant neoplasm arising from 
melanocytes within the epidermis or the nail 
bed. • Anatomic site is highly predictive of 
invasiveness and metastatic propensity: ◦ Digit 
and mucocutaneous junction melanomas tend 
to be malignant. ◦ Melanomas of haired-skin 
tend to behave in benign manner. • When 
malignant—occasionally invades bone (e.g., 
third phalanx) and metastasizes (lymph node, 
lungs, and other sites).
• Dogs—around 5% of all skin tumors. 
• Cats—<5% of all skin tumors. • Dogs, 
mean age 9 years, certain breeds more 
common—terriers (Scottish, Boston, and 
Airedale), schnauzers, cocker and springer 
spaniels, Irish setter, chow chow, retriever 
breeds, poodles, Doberman pinschers. • Cats, 
mean age 10–13 years, no breed predilection.
SIGNS
• Skin mass with variable growth rates, may be 
ulcerated and friable, usually solitary. 
• Develops anywhere; in dogs more common 
on face, trunk, feet, and scrotum; in cats more 
common on head, digit, pinna, and nose. 
• Benign—brown to black; varies from 
macules and plaques to firm, dome-shaped 
nodules, 0.5–2 cm in diameter, well 
demarcated. • Malignant—amelanotic to dark 
brown, gray, or black, often >2 cm in diameter 
and more invasive in surrounding tissues. 
• Lameness and pain if digit is involved and 
associated with infection or bone lysis. 
• Regional lymphadenomegaly possible.
  DIAGNOSIS
Distinguish amelanotic melanoma from poorly 
differentiated discrete cell tumors (mast cell 
tumor, lymphoma), various sarcomas (e.g., 
histiocytic, soft tissue sarcoma), carcinomas 
(especially basal cell), other benign changes 
(pyogranulomatous inflammation).
IMAGING
• Thoracic radiography recommended for 
evaluation of distant metastasis. • Advanced 
imaging (CT scan) is more sensitive to detect 
smaller distant metastases. • With digital 
melanoma, radiography of the lesion is 
recommended to determine if underlying bone 
(P3) is involved; bone lysis is less common 
with nailbed melanoma (approximately 10%) 
compared with squamous cell carcinoma 
(approximately 75%).DIAGNOSTIC PROCEDURES
aspirates (primary mass, draining lymph 
nodes). • Draining lymph nodes should be 
evaluated with cytology, regardless of their 
size and consistency upon palpation. • Tissue 
biopsies may be required to obtain definitive 
diagnosis (via histopathology). 
• Immunohistochemical markers—may help 
differentiate melanoma (especially amelanotic) 
from other tumors; may stain positive with 
Melan-A, S100, PNL2, HMB-45, vimentin; 
behavior (e.g., Ki67).
  TREATMENT
• Wide surgical excision—treatment of 
choice. • Amputation of digit (P3 and P2) 
with nailbed localization. 
• Lymphadenectomy of the draining lymph 
node might be indicated when regional 
metastasis confirmed or suspected and no 
evidence of detectable distant dissemination.
resection. • Palliative radiation therapy may 
be considered for inoperable tumors.
• Adjuvant chemotherapy (often carboplatin) 
recommended following excision of macro -
scopic malignant melanoma (primary tumor, 
metastatic regional lymph nodes). 
• Chemotherapy may still be advised if 
surgical excision is not possible, with a 
response rate approximating 30% on 
• Contact a veterinary oncologist for updates 
on novel therapeutic options or treatment 
regimens. • Multimodal analgesia 
recommended to control pain and discomfort.
attempted with varied success. • Therapeutic 
vaccination—injection of cDNA coding for a 
melanocyte-specific protein, tyrosinase, is 
considered safe and results in a measurable 
immune response in some patients.
• Cisplatin is contraindicated in cats. • Seek 
advice from an oncologist before initiating 
drugs (myelosuppression, specific toxicities, etc.).  FOLLOW-UP
metastasis—every 2–3 months following 
surgery or earlier if the owner believes the mass 
is returning; or if the patient is otherwise not 
normal. • 3-view thoracic radiography—at the 
time of rechecks and periodically thereafter.
Dogs
• Melanomas on the digit, footpad, scrotum, and 
mucocutaneous junctions are more frequently 
malignant. • Prognosis with benign cutaneous 
melanomas is excellent. • Median survival with 
malignant cutaneous or digit melanoma is 12 
months. • Breed differences in prognosis in some 
studies—majority of cutaneous melanomas in 
Doberman pinschers and miniature schnauzers 
behave in a benign fashion, and a majority of 
cutaneous melanomas in miniature poodles 
behave in a malignant fashion.
Cats
• 35–50% of melanomas reported to be 
malignant. • Median survival with melanoma 
of the skin or digit not well documented and 
reported to be 4.5 months after surgery. • Cats 
with auricular melanoma may have a more 
favorable prognosis compared to melanomas of 
other cutaneous sites or oral cavity.
SEE ALSO
Melanocytic T umors, Oral.
Chamel G, Abadie J, Albaric O, et al. 
Non-ocular melanomas in cats: a retrospective 
study of 30 cases. J Feline Med Surg 2017, 
19:351–357.
Henry CJ, Brewer WG Jr., Whitley EM, et al. 
Canine digital tumors: a veterinary 
cooperative oncology group retrospective 
study of 64 dogs. J Vet Intern Med 2005, 
19(5):720–724.

Canine and Feline, Seventh Edition  889
MMelena
  BASICS
Black, tarry appearance of feces caused by the 
presence of digested or oxidized blood.
Usually results from upper gastrointestinal (GI) 
bleeding (esophagus, stomach, small intestine), 
but can be associated with ingested blood from 
the oral cavity or respiratory tract. Rarely can be 
caused by bleeding in the cecum or colon.
• GI.
• Coagulation.
GENETICS
N/A
Unknown
Worldwide
Species
• More common in dog than cat.
None
Any age.
None
SIGNS
• Patients with clinically significant anemia 
may demonstrate lethargy, inappetence, 
weakness, collapse, mucous membrane pallor, 
and/or dyspnea.
• Patients with primary GI disease may 
demonstrate hypersalivation, dysphagia, 
regurgitation, vomiting with or without 
blood (frank blood or “coffee grounds” 
appearance), inappetence, weight loss, 
increased borborygmi, or diarrhea.
• Patients with respiratory tract hemorrhage 
may demonstrate epistaxis, sneezing, 
hemoptysis, mucous membrane pallor, 
weakness, and/or dyspnea.
• Patients with abnormal coagulation may 
demonstrate petechiae, ecchymoses, mucous 
membrane pallor, epistaxis, hematuria, 
hematochezia, hyphema, and/or weakness.
Depends on the underlying cause.
CAUSES
Primary GI Ulceration/Erosion
sarcoma.• Inflammatory bowel disease (IBD)—  
lymphoplasmacytic, eosinophilic, granulo­
matous, and/or histiocytic gastritis/enteritis.
• Benign polyps.
• Infectious—Bacterial ( Salmonella  spp., 
Clostridium perfringens , C. difficile ); fungal or 
fungal ­like (pythiosis, histoplasmosis), parasitic 
(Physaloptera, Ollulanus,  hookworms), viral 
(parvovirus, circovirus, distemper).
• Mechanical—foreign body.
• Inflammatory—acute and chronic gastritis; 
acute hemorrhagic diarrhea syndrome.
• Drugs—nonsteroidal anti ­inflammatory 
drugs (NSAIDs), corticosteroids.
• Toxins—ingestion of heavy metals, some 
plants, cleaners, etc.
Metabolic/Other Diseases That Cause GI 
Ulceration
• Neoplasia—gastrinoma, mast cell tumor.
• Shock, poor perfusion.
• Acute kidney injury or advanced chronic 
kidney disease.
• Hepatic disease/failure, intrahepatic 
portosystemic shunts.
Ingestion of Blood
• Diet (raw foods).
• Esophageal lesion—neoplasia, esophagitis.
• Oral or pharyngeal lesion—neoplasia, 
abscess.
• Nasal lesion—neoplasia, fungal rhinitis, 
inflammatory rhinitis, trauma.
• Respiratory lesion—lung lobe torsion, 
neoplasia, pneumonia, trauma (causing 
hemoptysis).
• Thrombocytopathia—congenital vs. 
acquired.
• von Willebrand disease.
• Clotting factor abnormalities—anti­
coagulant rodenticide ingestion, selected 
clotting factor deficiencies.
• Disseminated intravascular coagulation.
Arthritis, intervertebral disc disease or other 
conditions requiring use of NSAIDs or 
  DIAGNOSIS
• Medications that cause dark stool—
bismuth subsalicylate, oral iron therapy, 
sucralfate, barium sulfate, activated 
charcoal.
• Must distinguish primary intestinal from 
extraintestinal disease.CBC/BIOCHEMISTRY/URINALYSIS
• Microcytic, hypochromic, poorly 
regenerative anemia if chronic blood loss.
• Regenerative anemia in early blood 
loss—may be pre ­regenerative if <3–5 days.
• Panhypoproteinemia, hypocholesterolemia 
if significant blood loss or diffuse GI disease
• Thrombocytopenia—may be mild from 
consumption with GI bleeding; severe 
thrombocytopenia may be primary cause of 
bleeding.
• Neutrophilia in some patients.
• Biochemistry analysis may reveal extra­
intestinal cause of melena—renal failure, 
hepatic disease, hypoadrenocorticism. Increased 
blood urea nitrogen (BUN):creatinine ratio can 
be seen secondary to GI bleeding.
• Urinalysis may demonstrate hematuria in 
patients with coagulation defects.
• Prothrobin time/activated partial thrombo­
plastin time (PT/aPTT) may be prolonged 
• Buccal mucosal bleeding time tests primary 
hemostasis. Will be prolonged with thrombo­
cytopenia and anemia.
• Fecal centrifugation flotation may reveal 
• Diarrhea PCR panels for bacterial DNA 
and toxin genes in combination with ELISA 
testing for C. perfringens  enterotoxin and C. 
difficile  toxins A and B may be helpful but 
should be interpreted based on history, 
physical examination findings, environment, 
and risk factors.
• Parvo antigen testing.
• Serum cobalamin and folate may be useful 
to screen for diffuse GI disease.
• Rectal scraping may demonstrate fungal 
organisms ( Histoplasma  spp.).
hormone (ACTH) stimulation test abnor­
mally low with hypoadrenocorticism.
IMAGING
• Abdominal radiography may reveal a mass 
or foreign body, or abnormalities in renal or 
hepatic size/shape.
• Thoracic radiographs may identify 
esophageal foreign bodies, pulmonary or 
tracheobronchial lesions or metastatic disease.
• Nasal CT may demonstrate intranasal lesions.
• Ultrasonography may reveal a GI mass, loss 
of intestinal layering, evidence of GI 
ulceration (mucosal defect, intramural gas), 
alterations in hepatic echotexture and size, 
pancreatic changes suggestive of pancreatitis, 
or changes supportive of renal disease or 
• Upper GI barium series may delineate 
gastric or proximal small intestinal masses, 
ulceration, or filling defects; however, upper 
GI series is insensitive for detection of gastric 
and intestinal ulceration.

890  Blackwell’s Five-Minute Veterinary Consult  
MDIAGNOSTIC PROCEDURES
• Endoscopy allows visualization of masses 
and/or ulcers (esophageal, gastric, and/or 
duodenal), retrieval of esophageal or gastric 
foreign bodies, and procurement of biopsy 
samples.
• Retroflex and/or anterograde rhinoscopy 
may allow visualization of nasal lesions.
• T racheobronchoscopy allows visualization 
of large airway lesions.
• Capsule endoscopy may be useful for 
delineating sites of intestinal bleeding that 
cannot be visualized via flexible endoscopy.
  TREATMENT
• Inpatient—most patients admitted for 
work ­up and management with exception of 
animals with melena secondary to intestinal 
• T reat underlying disease—renal failure, 
hepatic disease, hypoadrenocorticism, 
respiratory disease, etc.
• Fluid replacement with balanced electrolyte 
solutions and potassium supplementation.
• Whole blood or packed red blood cell 
transfusions if anemia is severe.
• Whole blood, platelet concentrate or 
plasma transfusion if the patient has a 
ACTIVITY
Need for restriction varies with underlying 
disease.
DIET
Temporarily discontinue oral intake if 
vomiting is intractable.
Surgery may be required for severe gastro­
duodenal ulceration, neoplasia, or foreign 
bodies.  MEDICATIONS
• Varies with underlying disease.
• For known or suspected gastric ulceration:
◦ Proton pump inhibitors (PPI; e.g., 
omeprazole 1 mg/kg PO q12h, pantoprazole 
1 mg/kg IV q12h, esomeprazole 0.7 mg/kg 
IV q12h) are superior to H2 antagonists for 
acid suppression. PPIs should be tapered 
following chronic use >3–4 weeks (50% 
reduction weekly).
◦ Misoprostol (3–5 μg/kg PO q12h) for 
cases of NSAID ­induced gastric ulcers.
◦ Sucralfate (0.5–1 g PO q6–8h as a 
suspension) for esophagitis or gastric 
Avoid corticosteroids and NSAIDs in patients 
with gastroduodenal ulceration/erosion.
Misoprostol should not be used in pregnant 
animals.
• Antacids may cause decreased absorption of 
medications that require an acid pH for 
absorption.
• Sucralfate should be separated from meals 
or other medications by 2 hours.
H2­receptor antagonists (e.g., ranitidine 1–2 
mg/kg IV, SC, or PO q12h or famotidine 
0.5–1 mg/kg IV, SC, or PO q12h) may be 
used for acid suppression if PPIs are not 
  FOLLOW-UP
• Packed cell volume (PCV) 2–3 times daily 
until anemia stabilized, then weekly.
• Hydration daily if patient vomiting.
Use ulcerogenic drugs with caution. Avoid 
concurrent use of NSAIDs and glucocorticoids.POSSIBLE COMPLICATIONS
• Gastric or duodenal perforation resulting in 
• Hypovolemic shock and death if severe, 
acute blood loss.
N/A
N/A
Bacterial ( Clostridium  spp., Salmonella  spp.) 
and parasitic infectious causes are potentially 
zoonotic.
animals.
SYNONYMS
N/A
SEE ALSO
drug.
• PT/aPTT = prothrobin time/activated 
partial thromboplastin time.
acknowledge the prior contribution of Lisa E. 
Moore.Melena  (continued)

Canine and Feline, Seventh Edition  891
MMeningioma—Cats and Dogs
  BASICS
• T umor of the meninges. Most commonly 
affects meninges overlying the cerebrum. 
• Most common tumor of the canine brain 
and spinal cord. •  Most common tumor of 
the feline brain; second most common tumor 
of the feline spinal cord (most common being 
• Primary tumor arising from the arachnoid 
cap cells. •  Intradural–extramedullary 
location. •  Usually solitary masses; 
occasionally multiple (cats > dogs). •  May 
occur as plaque-like masses on the floor of the 
calvaria, paranasally, or retrobulbar space 
(rare, more common in dogs than in cats). 
• Causes neurologic deficits secondary to 
compression of the adjacent tissue. Progresses 
slowly, causing vasogenic edema and, 
occasionally, obstructive hydrocephalus or 
infarction. •  Most are cytologically  benign. In 
dogs, tend to be more invasive into brain 
parenchyma or surrounding vasculature, and 
can be considered biologically  malignant, 
unless aggressive surgical resection is possible 
(e.g., within the olfactory bulb).
Nervous—primary effects (e.g., infiltration 
and compression of adjacent structures) and 
secondary effects (e.g., edema, increased 
intracranial pressure [ICP], brain herniation).
• Reported incidence of brain tumors is 
14.5/100,000 dogs and 3.5/100,000 cats. 
Meningiomas account for approximately 22% 
of all canine brain tumors, and 59% of all 
feline brain tumors. •  17% of cats with 
intracranial meningioma have >1 tumor of 
the same type. •  Incidence of spinal tumors 
in dogs and cats—unknown; considerably less 
than that of brain tumors. Spinal meningi-
omas account for 14% of all canine meningi-
omas and 4% of all feline meningiomas.
Dogs
• Boxers and golden retrievers most 
commonly affected; dolichocephalic breeds 
may have an increased risk of intracranial 
meningioma; mesocephalic breeds may have a 
higher incidence of paranasal meningioma. 
• Most >7 years of age; median 9 years, range 
11 weeks–14 years; a spinal meningeal 
sarcoma was diagnosed in an 11-week-old 
Rottweiler. •  Slight predominance for 
females. •  Cystic meningiomas reported.Cats
• Domestic shorthair cats overrepresented. 
• Most >9 years of age; mean 12 years, range 
1–24 years; slight predominance for males.
SIGNS
• Vary with tumor location. •  Typically 
chronic and insidiously progressive over 
weeks to months. •  May be acute if vascular 
invasion results in focal ischemia or if edema 
develops rapidly. •  Lateralizing deficits 
predominate. •  Elevated ICP , cerebral edema, 
or brain herniation may cause multifocal 
deficits, making localization of a focal mass/
lesion difficult based on clinical signs.
May be prolonged history of vague signs until 
compensatory mechanisms (e.g., decreased 
cerebrospinal fluid [CSF] and blood volume) 
are overwhelmed, followed by rapid 
progression of clinical signs.
Intracranial
• Dogs—late-onset seizures is the most 
common presenting sign. •  Cats—abnormal 
behavior and mentation are the most 
common presenting signs. Nonspecific signs 
include lethargy, inappetence, and anorexia. 
Seizures less common than in dogs.
Intraspinal
• Neck or back pain. •  Progressive 
incoordination and weakness, which may 
worsen with exercise.
• Cerebral disease is most common, causing 
abnormal behavior and mentation; circling 
or head-pressing; contralateral hemi-neglect, 
hemianopsia, facial paresis, facial and 
thoracic hypesthesia and conscious proprio -
ceptive deficits; seizures. •  Brainstem—
alterations of consciousness; abnormal gait; 
ipsilateral proprioceptive and cranial nerve 
deficits in cranial nerves III to XII; central 
vestibular abnormalities. •  Cerebellum—
ataxia and dysmetria; intention tremors; 
truncal sway; broad-based stance; lack of 
menace responses with normal vision, and 
pupillary light and palpebral reflexes. 
• Orbital—exophthalmos, orbital swelling, 
prolapsed globe; blindness in the affected 
eye; fundic abnormalities.
• Paraspinal or radicular pain referable to the 
region of spinal column affected. •  Ataxia 
and paresis caudal to the level of the lesion.
CAUSES
• Unknown. •  Documentation in young cats 
with mucopolysaccharidosis type I suggests a 
causal relationship.  DIAGNOSIS
• Metabolic or toxic encephalopathy—may 
also present with seizures or mentation 
changes and normal neurologic exam; 
differentiate with brain imaging. •  Other 
primary CNS (e.g., glioma, pituitary, 
nephroblastoma) or secondary (e.g., 
lymphoma, extensional, metastatic) 
tumors—may have more rapid onset and 
progression of signs; differentiate with 
brain or spinal imaging. •  Granulomatous 
meningoencephalitis—may cause 
progressive focal deficits in dogs; 
differentiate based on age and further 
diagnostics, such as imaging and CSF 
analysis. •  Nerve sheath tumors, gliomas, 
lymphoma, focal meningomyelitis, type II 
intervertebral disc disease, degenerative 
myelopathy—differentiate by spinal cord 
imaging. •  Cryptococcus  granuloma—
reported to have same appearance on CT as 
a meningioma in a cat.
IMAGING
intracranial and spinal disease. •  MRI—often 
hyperintense on T2-weighted images (T2WI), 
isointense on T1-weighted images (T1WI), and 
uniformly contrast-enhancing mass lesion of 
the brain or spinal cord; broad-based, with 
extra-axial attachment. A ‘dural tail’ is a 
characteristic feature. If present, ‘dural tail’ 
helps to differentiate an intraventricular 
meningioma from a choroid plexus tumor. 
Spinal cord swelling may make the distinction 
between intradural/extramedullary and 
intramedullary difficult. •  CT—often 
homogeneous contrast enhancement of 
well-circumscribed mass lesion. •  Skull 
radiography and CT—may reveal hyperostosis 
of the calvaria adjacent to the meningioma. 
Calcification of the mass causes increased tissue 
density. Hyperostosis may be seen in cats. 
• Spinal radiography—usually normal with 
intraspinal meningioma; can be helpful to rule 
out bony lesions. •  Myelography—typically 
reveals an intradural–extramedullary mass and 
interruption of the normal flow of contrast at 
the tumor. ‘Golf tee’ appearance can be present 
with both nerve sheath tumor and meningi -
oma. Differentiation requires biopsy.
• CSF analysis—infrequently performed 
because diagnostic imaging is diagnostic. If 
performed, normal-to-high protein concentra -
tion with possible neutrophilic or mixed

892  Blackwell’s Five-Minute Veterinary Consult  
Mpleocytosis. Should not be considered unless 
CT or MRI have been performed. 
Contraindicated with increased ICP , as 
collection of CSF increases risk of brain 
herniation and consequent neurologic 
decompensation. •  Electroencephalography—  
reveals slow-wave, medium--to-high-voltage 
activity, indicating cortical depression. Paroxysmal 
waveforms characteristic of seizure activity 
may be evident. •  Biopsy—necessary for 
definitive diagnosis; perform intraoperatively or, 
for intracranial tumors, using a CT-guided 
stereotactic system.
  TREATMENT
• Inpatient—necessary if dehydration, 
anorexia, disequilibrium, and/or frequent or 
life-threatening seizures. •  Surgical excision—
for definitive management; usually successful 
if the tumor is accessible. Incomplete 
excision is common, particularly for 
intracranial meningiomas in dogs, 
intraspinal meningiomas in cats, and in 
tumors ventral to the spinal cord. 
• Fractionated conventional radiation 
therapy—15–20 treatments over 3–4 weeks, 
following incomplete excision, if excision 
not possible, or if a less invasive approach is 
desired. When combined with surgery, 
radiation is associated with prolonged 
survival time in canine intracranial and 
intraspinal meningiomas compared to 
surgery alone, and delays or prevents local 
recurrence of disease. Given the success of 
complete surgical excision of intracranial 
meningiomas in cats, radiation is rarely 
necessary. Feline intracranial meningiomas 
are likely radiation sensitive, but data are 
lacking. It should be considered when 
surgery is not an option •  Stereotactic 
radiosurgery (SRS)—high dose of radiation 
delivered to tumor with sub-millimeter 
accuracy. A steep dose-gradient limits 
exposure of normal tissue and reduces side 
effects of radiation. Can be conducted on an 
outpatient basis in 1–5 treatments delivered 
on consecutive days. The best candidates are 
those who are stable or able to be stabilized 
with steroids prior to the procedure. SRS 
significantly decreases tumor volume, but 
occurs slowly. SRS should be distinguished 
from intensity modulated radiation therapy 
(IMRT) delivered in 3–5 fractions (hypo -
fractionated IMRT), the former being more 
accurate. •  Chemotherapy—may be 
associated with prolonged survival after 
incomplete excision, post-radiation, or as 
sole agent. Hydroxyurea inhibits DNA 
synthesis, leading to cell death during the S phase of the cell cycle. Hydroxyurea shows 
effectiveness in humans with intracranial 
meningiomas and is commonly used in 
veterinary medicine, but controlled studies 
are lacking. •  Medical management—
antiepileptic drugs and corticosteroids are 
palliative, without effect on the primary 
disease process. Neither radiation or 
chemotherapy aid directly in control of 
edema or of neurologic signs such as 
seizures.
• Fluids—avoid overzealous fluid admini -
stration, as this may exacerbate cerebral 
edema and neurologic deficits. •  Use caution 
with jugular compression during venipuncture 
or when positioning for surgery to avoid 
increases in ICP .
Cerebral Edema
• Corticosteroids—improve neurologic 
deficits associated with vasogenic edema. 
• Stuporous, severely ataxic, or showing 
signs of herniation—methylprednisolone 
sodium succinate 30 mg/kg IV or 
dexamethasone sodium phosphate 0.1 mg/
kg IV. •  Continued deterioration or no 
improvement—20% mannitol solution 
0.5–1 g/kg IV over 15–20 minutes. 
Furosemide 2 mg/kg IV acts synergistically 
with mannitol and can be added if needed. 
Hypertonic saline 3–5 mL/kg may be used 
as an alternative or in addition to mannitol. 
Dexamethasone 0.05–0.1 mg/kg q24h IV. 
• Once patient is stable—dexamethasone 
0.05–0.1 mg/kg q24h or in divided daily 
doses PO or prednisone 0.25–0.5 mg/kg 
PO q12h; then taper to lowest effective 
dose.
Seizures
• Antiepileptic drugs—mandatory if isolated 
seizures >1/month, cluster seizures, or status; 
recommended if any seizure activity in animal 
with meningioma, and possibly prophylactically 
in animals with forebrain meningioma. 
• Maintenance treatment—phenobarbital 
(first choice in dogs and cats) 2–3 mg/kg IV 
or PO q12h; or zonisamide 5–10 mg/kg 
q12h PO (dogs or cats); or levetiracetam 
20–30 mg/kg q8h IV or PO as starting dose; 
if extended release levetiracetam q12h PO 
(dogs or cats). •  Cluster seizures or status—
diazepam 0.25–5 mg/kg/h CRI; or 
phenobarbital 4 mg/kg IV q2–6h until 12–16 
mg/kg total loading dose; or midazolam 
0.2–0.4 mg/kg/h CRI; or levetiracetam 60 
mg/kg IV.Chemotherapy
Hydroxyurea—150 mg/kg/week (dogs) and 
75 mg/kg/week (cats).
  FOLLOW-UP
• Mannitol—monitor serum osmolality 
and electrolytes, particularly with repeated 
administration. Maintain osmolality at or 
below 320 mOsm/L to reduce risk of renal 
failure due to renal vasoconstriction. 
• Corticosteroids—perform serial neuro -
logic examinations; marked neurologic 
improvement is possible within 24–48 
hours after initiation of treatment with 
corticosteroids. •  Antiepileptic drugs—
evaluate serum pheno  barbital levels 3 weeks 
after initiation of therapy; evaluate liver 
enzymes every 6 months while on pheno -
barbital. •  Hydroxyurea—monitor CBC 
with platelet count before starting, at 2 
weeks, 6 weeks then CBC, chemistry 
profile every 3–4 months. May lead to 
vomiting or diarrhea, stomatitis, sloughing 
of nails, alopecia, and dysuria; most serious 
effects are bone marrow depression and 
pulmonary fibrosis.
Dogs
• Surgical excision—outcome depends on 
surgical technique. Reported median survival 
time is 6.7 months (3 dogs). Survival increased 
with regional cerebral resection (16.5 months in 
6 dogs), or with the use of a surgical aspirator 
(41.8 months in 17 dogs) or with endoscopy-
assisted tumor removal (70.1 months with 
forebrain and 23.4 months with caudal brain 
meningioma in 33 dogs). •  Surgical excision 
with postoperative fractionated radiation 
therapy—reported median survival times of 
16.5 months–3 years. •  Radiation therapy 
alone—reported median survival times of 
5–12.5 months with conventional radiation. 
• Chemotherapy using hydroxyurea—reported 
mean survival time of 7–8 months. •  SRS (e.g., 
Frameless SRS, Varian T rilogy/T ruBeam, 
Cyberknife)—reported mean survival time of 
16.4 months in 38 dogs, and 19.8 months in 20 
dogs. •  Medical management—reported 
median survival time of 3–4 months in dogs 
treated with palliative therapy alone.
• Surgical excision—reported mean survival 
time of 19 months in 8 dogs. •  Surgical 
excision with postoperative radiation 
therapy—reported median survival time of 
13.5 months in 6 dogs.Meningioma—Cats and Dogs  (continued)

Canine and Feline, Seventh Edition  893
MCats
• Surgical excision—good prognosis. Surgery 
is curative in 75–80% of patients that 
undergo surgical excision. Reported mean 
survival time 22–27 months. Seizure activity 
may persist despite successful excision. 
Recurrence, if it occurs, is usually in same 
location. •  Medical management—
neurologic deficits become more severe with 
time. Progression is often slow because 
meningiomas are slow growing.
• Surgical excision—survival time is shorter than 
that of cats with cerebral meningiomas: reported 
median survival times of 14.2 months in 16 cats 
and 17.3 months in 26 cats. •  Corticosteroids—
palliative in the short term. Thoracolumbar 
disease progresses to paralysis and inability to 
control urination (urinary retention and possibly 
bladder atony and cystitis).  MISCELLANEOUS
Brain tumor should be suspected in dogs and 
cats >5 years with recent onset of seizures and 
unremarkable extracranial diagnostic workup 
for seizures.
• IMRT = intensity modulated radiation 
therapy.
• SRS = stereotactic radiosurgery.
• T1WI = T1-weighted images.
• T2WI = T2-weighted images.
to Canine and Feline Neurology, 3rd ed. Ames, IA: Wiley-Blackwell, 2016, pp. 
183–191.
Larue SM, Gordon IK. Radiation therapy. In: 
W.B. Saunders, 2013, pp. 180–197.
Motta L, Mandara MT, Skerritt GC. Canine 
and feline intracranial meningiomas: an 
updated review. Vet J 2012, 
192(2):153–165.
Petersen SA, Sturges BK, Dickinson PJ, et al. 
Canine intraspinal meningiomas: imaging 
features, histopathologic classification, and 
long-term outcome in 34 dogs. J Vet Intern 
Med 2008, 22:946–953.
Sessums K, Mariani C. Intracranial 
meningioma in dogs and cats: a comparative 
review. Compend Cont Educ Vet 2009, 
7:330–339.
Authors  Richard J. Joseph and Anne E. 
Buglione(continued)  Meningioma—Cats and Dogs

M
894  Blackwell’s Five-Minute Veterinary Consult  
MMeningitis/Meningoencephalitis/Meningomyelitis, Bacterial
  BASICS
• Meningitis—inflammation of the meninges.
• Meningoencephalitis—inflammation of the 
meninges and brain.
• Meningomyelitis—inflammation of the 
• Bacterial infection of the CNS can occur by 
direct extension from an infected extraneural 
site or when bacteria are introduced by 
penetrating trauma or a migrating foreign body.
• Hematogenous spread of bacteria to the 
CNS from mucous membrane colonization 
or a distant pyogenic focus can occur. This is 
the most common cause in septicemic 
neonates and immunocompromised patients.
• Neurological deficits often develop from 
secondary inflammation but may be from 
bacterial invasion of the brain or spinal cord 
• Inflammatory debris and adhesions can 
obstruct cerebrospinal fluid (CSF) flow, 
leading to secondary hydrocephalus.
• Nervous—meninges, brain, or spinal cord.
• Multisystemic signs—may be present when 
the infection originates in an extraneural site 
or when the systemic inflammatory response 
is severe.
Rare
Species
Any age.
Males and females affected equally.
SIGNS
• Patients are often systemically ill.
• Shock, hypotension, and disseminated 
intravascular coagulation (DIC) are often 
found in septicemic patients.
• CNS signs may be profound and rapidly 
progressive.
• Pyrexia in approximately 50%.
• Cervical rigidity and hyperesthesia—
especially with meningitis.
• Neurologic deficits—reflect the location of the 
involved spinal cord or brain parenchyma (e.g., 
altered mentation, cranial nerve deficits, postural 
reaction deficits, ataxia, paresis, seizures).
• May find an extraneural site of underlying 
bacterial infection.• Vomiting.
• Bradycardia with systemic hypertension 
suggests increased intracranial pressure.
CAUSES
• Meningoencephalitis—can be secondary to 
local extension from otitis media/interna or 
infection of the eye, retrobulbar space, 
sinuses, or nasal passages or due to direct 
inoculation by traumatic skull fractures or 
migrating foreign bodies.
• Meningomyelitis—can be secondary to 
discospondylitis or vertebral osteomyelitis.
• Hematogenous spread of bacterial infection 
to the CNS can occur in neonates with 
omphalophlebitis, immunocompromised 
patients, or in dogs with bacterial endocarditis, 
prostatitis, discospondylitis, pneumonia, 
urinary tract infections or severe gastroenteritis.
• The point of origin is not always found.
• Untreated bacterial infection.
• Immunocompromised state.
• Injury involving the CNS or adjacent 
  DIAGNOSIS
Infectious Meningitis (Nonbacterial)
• Canine distemper, toxoplasmosis, 
neosporosis, cryptococcosis, blastomycosis, 
rickettsial organisms, West Nile virus, and 
feline infectious peritonitis all cause 
meningitis/meningoencephalitis that can be 
difficult to distinguish from bacterial disease.
• CSF—inflammatory with a variable 
lymphocytic, mixed mononuclear or 
neutrophilic pleocytosis depending on the 
specific infectious etiology.
• Antemortem diagnosis suspected based on 
typical clinical findings and identification of 
affected extraneural sites.
• Diagnosis is by identifying organisms in the 
CSF or in extraneural sites (using cytology, 
culture, or PCR) and by serology.
Steroid-Responsive Meningitis–Arteritis 
(Aseptic Meningitis)
• Observed mainly in young (6–19 months) 
adult large-breed dogs.
• Beagles, boxers, Bernese mountain dogs, 
German shorthaired pointers, Weimaraners, 
and Nova Scotia duck tolling retrievers are 
predisposed; any breed can be affected.
• Cervical pain without neurologic deficits is 
• Fever occurs in 60–80% of affected dogs. 
Signs may wax and wane initially.
• Affected dogs are systemically normal.
• CSF—increased nucleated cell count 
and protein. Neutrophilic pleocytosis in acute cases, mononuclear cells may 
predominate in chronic cases. Negative 
bacterial culture.
• Serum and CSF IgA increased.
• Dramatic response to corticosteroid 
Meningoencephalitis of Unknown Origin 
(MUO)
• Idiopathic noninfectious inflammatory 
diseases of the brain, spinal cord, and 
meninges in dogs including granulomatous 
meningoencephalomyelitis (GME), 
necrotizing meningoencephalitis (NME), and 
necrotizing leukoencephalitis (NLE). A 
definitive diagnosis requires histopathology.
• Young adult (3–7 years), female, small-
breed dogs are most commonly affected.
• Neurologic abnormalities reflect the 
location of the lesion(s).
• MRI—usually multifocal parenchymal 
lesions with variable contrast enhancement.
• CSF— pleocytosis with >50% mono -
nuclear cells and increased protein 
• CSF culture—negative.
Primary CNS Neoplasia
• History protracted; neurologic signs 
limited to the CNS; standard laboratory 
tests normal.
• Diagnosis by CT, MRI, CSF analysis, and 
biopsy.
• Leukocytosis is common; left-shift or 
toxicity may be seen. Thrombocytopenia may 
be present in septicemic patients.
• Biochemical changes are variable and often 
nonspecific.
• Pyuria and bacteriuria occur in patients 
with underlying urinary tract or prostatic 
infection and in some bacteremic animals.
• Serologic tests—may differentiate bacterial 
from other infectious diseases; in cats, 
toxoplasma titer may be positive without 
clinical disease.
• Cytology of infected tissues—skin, eyes, 
nasal discharge, lymph node, tracheal wash; 
helps identify nonbacterial causative organ -
isms, especially in patients with fungal disease.
• Blood culture—positive in 30% of dogs 
with bacterial meningitis.
IMAGING
• Thorax radiography and abdominal 
ultrasound—to identify underlying infection 
or other significant disease.
• Vertebral column radiography—disco -
spondylitis may be identified as a focus of 
• Head CT—may identify infected sinus, nasal 
cavity, or middle and inner ear as initiating site. 
Inflamed regions of brain parenchyma and 
meninges usually enhance with contrast.

Canine and Feline, Seventh Edition  895
MM• Echocardiography—performed when 
valvular endocarditis suspected based on 
murmur/arrhythmia.
• MRI with contrast—documents brain, 
spinal cord and meningeal inflammation and 
can identify extraneural sites of infection 
(sinus, nasal, ear).
• Collection—a concern in animals with 
altered mentation suggesting high intracranial 
pressure, because the procedure may precipitate 
brain herniation. Pretreat with mannitol.
• Analysis—neutrophilic pleocytosis with 
high protein concentration; neutrophils may 
appear toxic or degenerated and intracellular 
bacteria are occasionally seen; often difficult 
to differentiate aseptic from bacterial 
meningitis cytologically.
• Culture—aerobic or anaerobic; may be 
positive (<40%)—inoculation of CSF into broth 
enrichment media improves diagnostic yield.
• Universal bacterial PCR assay of CSF can 
be used to identify DNA from causative 
organisms when bacterial culture is negative.
• May note subdural empyema, or purulent 
material on the surface of the brain or 
• Asymmetric diffuse or multifocal brain or 
spinal cord and meningeal suppurative 
• Culture of affected neurologic tissue—
positive in >75% of patients.
  TREATMENT
Inpatient—treat aggressively; intensive care 
monitoring often necessary.
Fluid therapy and supportive care.
Inform client that rapid and aggressive 
treatment is important and that the prognosis 
for recovery is guarded.
• Bactericidal agents that achieve therapeutic 
concentrations within CSF are most desirable—  lipid-soluble drugs with small molecular size, 
low protein binding, and a low degree of 
ionization at physiologic pH recommended.
• Cultures—CSF , blood, urine, primary site; 
determine drug sensitivity; until cultures 
identify the organism choose a broad-
spectrum agent that penetrates the blood–
brain barrier (BBB).
• Recommended drugs include third-generation 
cephalosporins (moxalactam, ceftriaxone, 
cefotaxime), fluoroquinolones, trimethoprim-
sulfonamides, doxycycline and metronidazole.
• Penicillin, ampicillin, amoxicillin-clavulanate, 
and carbapenems enter the CNS when there is 
inflammation and are a good choice to use in 
combination with another antibiotic that will 
continue to cross the BBB as inflammation 
resolves, such as trimethoprim-sulfonamides. 
Ampicillin may achieve high CSF concentra -
tions even without inflammation.
• Metronidazole reaches high levels in CSF , 
brain parenchyma, and abscesses and 
demonstrates the best bactericidal activity 
against anaerobes.
• Clindamycin is lipid soluble but does not 
readily cross the BBB. Concentrations in 
brain and spinal cord are adequate for 
treatment of Toxoplasma  and Neospora  
infections but insufficient for treating most 
CNS bacterial infections.
• Administer antibiotics intravenously for 
3–5 days to achieve high CSF concentrations 
rapidly, then maintain on oral therapy.
• Immediate IV therapy can be based on 
cytology; penicillin for Gram-positive 
infections, fluoroquinolone or third-generation 
cephalosporin for Gram-negative infections.
Antiepileptic Drugs
• Indicated for seizures.
• Long-term use may be needed.
• Most CNS dysfunction is due to 
• May administer dexamethasone 0.1 mg/kg 
q24h for several days but use is somewhat 
Aminoglycosides and first-generation 
cephalosporins—do not penetrate the BBB 
even in the presence of inflamed meninges.
  FOLLOW-UP
Monitor for nervous system signs, fever, 
leukocytosis, and systemic signs.PREVENTION/AVOIDANCE
T reat local infections adjacent to the CNS 
(e.g., infections of the eyes, ears, sinuses, 
nose, and vertebral column) early and 
aggressively to prevent extension to the CNS.
Damage to the brain and spinal cord may be 
irreversible.
• Response to antibiotics—variable; 
prognosis guarded.
• Many patients die despite treatment
• Residual neurologic deficits are possible.
• T reatment for at least 4 weeks after 
resolution of all signs is recommended.
SEE ALSO
• Meningoencephalomyelitis of Unknown 
Etiology (MUE).
• Steroid-Responsive Meningitis–Arteritis— 
Dogs.
• NLE = necrotizing leukoencephalitis.
Greene CE. Bacterial meningits. In: Sykes JE, 
ed., Canine and Feline Infectious Diseases. 
St. Louis, MO: Saunders Elsevier, 2014, 
pp. 886–892.
Radaelli ST, Platt SR. Bacterial 
menigoencephalomyelitis in dogs: a 
retrospective study in 23 cases (1990–
1999). J Vet Intern Med 2002, 
16:159–163.
Tipold A, Stein VM. Inflammatory diseases 
of the spine in small animals. Vet Clin Small 
Anim 2010, 40:871–879.
Authors  Danielle Zwueste and Susan M. 
Taylor(continued)  Meningitis/Meningoencephalitis/Meningomyelitis, Bacterial

896  Blackwell’s Five-Minute Veterinary Consult  
MMeningoencephalomyelitis, Eosinophilic
  BASICS
OVERVIEW
Although eosinophilic 
meningoencephalomyelitis (EME) can be 
associated with meningitis, encephalitis, and 
myelitis as a result of CNS infection or parasitic 
migration, in most cases, no underlying cause 
can be found. Idiopathic EME occurs in young 
to middle-aged large-breed dogs and resolves in 
many cases following steroid treatment.
• Dog and rarely cat. •  Idiopathic EME—
often larger dogs (>25 kg); Rottweilers and 
golden retrievers predisposed. •  Mean age—4 
years (2 months–13 years).
SIGNS
• Vary with CNS location and severity. 
• Neurologic deficits—most frequently 
associated with cranium, infrequently with 
spinal cord and rarely with cranial nerve 
• Idiopathic EME (unknown cause)—
majority of reported cases. •  Infectious—
Dirofilaria immitis  and cuterebra myiasis in 
cats; Toxoplasma gondii , Neospora  spp., 
Prototheca  spp., Cryptococcus  spp., and 
nematode migration with Baylisascaris 
procyonis  in dogs. •  Angiostrongylus —dogs in 
Australia. •  Intervertebral disc disease 
probably as allergic response to disc material.
  DIAGNOSIS
• Cannot be differentiated from other 
encephalitides solely on clinical signs; CSF 
analysis must be done. •  Idiopathic EME—
negative serologic test results; marked CSF 
eosinophilic pleocytosis (20–95%); usually 
steroid-responsive. •  Infectious diseases—
identified on presence of systemic signs, 
blood work, fecal sample, CSF , serum/CSF 
serology, and imaging.
• Peripheral eosinophilia—may or may not 
be present. •  Biochemistry and urinalysis—
usually normal with idiopathic disease; 
eosinophilia, liver enzyme activity, and 
creatine kinase may be elevated in infectious 
diseases.
• Serology—to rule out suspected infectious 
diseases. •  Fecal flotation and sedimentation—
to rule out migratory parasite.IMAGING
ultrasound—to rule out systemic involvement. 
• MRI—variable; focal mass lesions, diffuse 
parenchymal abnormalities, postcontrast 
diffuse meningeal enhancement; abnormalities 
depend on cause and location of lesion.
• Eosinophilic pleocytosis significant when 
>10%. •  Presence of eosinophilic pleocytosis by 
itself cannot differentiate idiopathic EME from 
infection causing CSF eosinophilic pleocytosis. 
• Idiopathic EME—total nucleated cell count 
4–3880 cells/ μL (median 99 cells/mL; reference 
<0.003) with 22–95% eosinophils. 
• Infections—62–4740 cells/mL (median 875 
cells/mL) with 30–95% eosinophils.
CSF Serologic Testing
• If CSF eosinophils >10%, look for parasitic 
and fungal disease. •  Test for heartworm, 
Neospora caninum , Toxoplasma gondii , and 
Cryptococcus neoformans .
• CSF eosinophilic pleocytosis does not 
necessarily correlate with eosinophils observed in 
CNS parenchyma. •  Wide variety of pathologic 
findings may indicate multiple causes, or the 
same disease taken at different times.
  TREATMENT
• Usually inpatient, because of severity of clinical 
signs. •  Activity—as tolerated. •  Regular diet.
• Idiopathic disease—steroid administration; 
dexamethasone (0.2 mg/kg q24h for 1 day; then 
0.15 mg/kg q24h for 6 days); follow with 
prednisone (0.5 mg/kg q24h for 8 weeks); then 
slowly wean patient off prednisone over 8 
weeks–6 months depending on clinical response. 
• Protozoal disease—clindamycin, sulfonamides, 
and pyrimethamine. •  Heartworm—microfilarial 
migration to the CNS is rare; no available 
treatment other than supportive.
• Important to differentiate idiopathic EME 
from infection as treatment greatly differs—
immunosuppressive dose of steroids vs. 
anti-organism treatment. •  Steroid should be 
used with caution if diagnosis has not been 
substantiated.  FOLLOW-UP
Inpatient—repeat neurologic examination 
every 6 hours to monitor progress.
Steroid treatment should not be stopped even 
if the animal is back to normal within a few 
days. A minimum of 8 weeks followed by 
tapering of the medication over as many 
weeks is mandatory.
• Recurrence may occur following cessation 
of medication. •  Ensure treatment dosage is 
adequate and reinstate for a longer period.
• Idiopathic disease—good prognosis in most 
cases with early treatment; improvement 
usually seen in the first 72 hours; full recovery 
in 2–6 months. Some patients continue to 
deteriorate despite steroids, and die. 
• Protozoal and fungal diseases—poor-to-
grave prognosis. •  Larval migration—
prognosis guarded to poor and depends on 
location of the lesion; signs may resolve, but 
larvae often continue to migrate and death 
may ensue. •  Degradation of eosinophils is 
toxic to nervous tissue; patient may have 
permanent deficits from not only the primary 
disease but also cell death.
Idiopathic EME is more frequent in young to 
middle-aged larger dog breeds (>25 kg).
SEE ALSO
Encephalitis
• EME = eosinophilic meningoencephomyelitis.
Cardy TJA, Cornelis I. Clinical presentation and 
magnetic resonance imaging findings in 11 
dogs with eosinophilic meningoencephalitis of 
unknown aetiology. J Small Anim Pract. 2018, 
59(7):422–431.
Williams JH, Köster LS, Naidoo V, et al. 
Review of idiopathic eosinophilic 
meningitis in dogs and cats, with a detailed 
description of two recent cases in dogs. J S 
Afr Vet Assoc 2008, 79(4):194–204.
Windsor RC, Sturges BK, Vernau KM, et al. 
Cerebrospinal fluid eosinophilia in dogs. J 
Vet Intern Med 2009, 23(2):275–281.
Author  Joane M. Parent

Canine and Feline, Seventh Edition  897
MMeningoencephalomyelitis of Unknown Etiology (MUE)
  BASICS
Meningoencephalomyelitis of unknown 
etiology (MUE) is a broad term used to 
describe inflammatory disorders that affect the 
CNS focally, diffusely, or multifocally. In the 
past, the majority of CNS inflammatory 
disorders were categorized as granulomatous 
meningoencephalomyelitis (GME). As a 
result, multiple less serious viral and idiopathic 
disorders were frequently erroneously 
diagnosed as GME. The appropriate clinical 
term to describe cases in which CNS 
inflammation is suspected is now considered 
MUE or meningioencephalitis of unknown 
etiology (MUO).
• Unknown. Although a specific etiologic 
agent is not recognized, in the majority of 
cases, viral and immune causes are strongly 
suspected. •  Three clinicopathologic forms 
are recognized: ocular, multifocal (brain or 
brain and spinal cord), and focal (single focus 
in the brain or spinal cord).
• Nervous. •  Ophthalmic.
GENETICS
Not proven.
Unknown. Since brain biopsies are rarely 
obtained, a presumptive diagnosis is made in 
most cases.
Worldwide
Any breed can develop MUE. Smaller toy 
breeds may be overrepresented and can be less 
responsive to therapy. However, the condition 
also occurs in medium and large-breed dogs.
• Mean—5 years. •  Range—6 months–10 
years.
Slightly higher prevalence in females.
SIGNS
• Depend on the form of the disease and 
neuroanatomic localization. •  Cerebral 
form—frequently results in seizure activity. 
• Ocular form—acute onset of blindness with 
dilated, unresponsive pupils. •  Focal 
form— cerebral lesion : disorientation, behavio -
ral changes, seizures, cortical blindness, 
compulsive circling, head pressing; brainstem 
lesion : somnolence, cranial nerve deficits (most 
commonly facial and vestibular dysfunction), 
ipsilateral hemiparesis; spinal cord : neck pain, 
tetraparesis (C1–C5 or C6–T2 lesions) or paraparesis (T3–L3 or L4–S2 lesions) and 
proprioceptive ataxia. In some patients the 
clinical signs can be unspecific and vague, 
delaying a prompt diagnosis and timely 
therapy.
CAUSES
Unknown
• Unknown. •  Some dogs develop clinical 
signs within 5–15 days of vaccination.
  DIAGNOSIS
• The combination of history, neurologic 
examination, CSF analysis, and MRI results 
usually lead to a presumptive diagnosis of 
inflammatory disease, but defining the cause 
of the inflammation can be problematic. •  It 
is possible that some dogs surviving 
inflammatory CNS disease have lesions 
compatible with GME, but post-mortem 
studies are not available to prove it. 
Alternatively, dogs who survive CNS 
inflammatory disease could have been 
suffering from other type of less serious viral 
or idiopathic inflammatory disease. Therefore 
the current accepted medical term to group 
these categories is MUE. •  Infectious 
inflammatory diseases—viral (distemper 
virus, other viruses); fungal ( Blastomyces 
dermatitidis , Coccidioides  spp., Cryptococcus 
neoformans ); rickettsial ( Rickettsia rickettsii ); 
bacterial ( Ehrlichia  spp., E. coli , Streptococcus ); 
protozoal ( Neospora caninum , Toxoplasma 
gondii ). • Other inflammatory disease—
necrotizing encephalitis of the Yorkshire 
terrier, Maltese, and pug; immune-mediated 
steroid-responsive meningitis (beagles, 
Bernese mountain dogs, Nova Scotia duck 
tolling retrievers, Weimaraners, boxers). 
• Sudden acquired retinal degeneration. 
• Brain tumor—meningioma, glioma, 
choroids plexus papilloma, lymphoma. 
• Subatlantoaxial luxation. •  Caudo-occipital 
malformation syndrome (COMS).
Serologic testing to rule out infectious CNS 
diseases.
IMAGING
MRI—method of choice; abnormalities are 
variable and consist of solitary, multiple, or 
circumscribed mass lesions. Multiple areas of 
heterogeneous contrast enhancement are 
frequent in the multifocal form of the disease. 
Other findings include mass effect with 
midline shift, obstructive hydrocephalus, 
white matter edema, and effacement of the 
sulci. Usually MRI lesions are characterized as hypointense in T1-weighted and hyperintense 
in T2-weighted images. Necrotic lesions are 
recognized by a center of hypointensity with a 
peripheral ring of enhancement.
• Reference range—white cell count (0–3 
cells/μL); protein concentration (0–30 mg/
dL). •  Helps confirm presence of inflamma -
tory disease but rarely demonstrates a definitive 
cause. The following are only guidelines, as 
significant overlap exists regarding CSF 
cytology of different inflammatory disorders. 
• Inflammatory diseases—white cell count 
and protein concentration usually increased. 
Even with a normal cell count, presence of an 
abnormal cell population (e.g., macrophages) 
should be taken into consideration as evidence 
of pathology. •  Usually, mononuclear pleocytosis; 
however, polymorphonuclear pleo  cytosis, or a 
normal CSF can be present. •  Bacterial (rare 
in dogs)—marked polymorphonuclear 
pleocytosis. •  Fungal, protozoal infections—
mixed pleocytosis (mononuclear and 
polymorphonuclear); rarely a fungal organism 
(Cryptococcus neoformans  or Blastomyces 
dermatitidis ) is identified. •  Viral infections—
mononuclear pleocytosis.
Brain Biopsy
Brain biopsy is the only procedure that can 
confirm conclusively a diagnosis of MUE. 
Due to morbidity, mortality, and cost 
associated with brain biopsy the test is not 
performed routinely. It is important to note 
that GME is not a clinical diagnosis but a 
term to describe findings at post-mortem. 
The term should not be used as clinical 
diagnosis, to avoid confusion.
• Hallmark feature—dense perivascular 
distribution of mononuclear infiltrates 
(lymphocytes, monocytes, and plasma cells). 
• Macroscopically, discoloration and 
softening of affected tissue sometimes 
evident.
  TREATMENT
• Stable patients can be discharged with 
recommended treatment. •  Inpatient—for 
severely affected dogs; monitor patient closely 
for progression of neurologic deficits. •  In 
severe cases, sequential assessment of pupil 
size and reaction to light, and mentation are 
helpful to determine risk of herniation.
• IV fluids for the anorexic patient. Take care 
not to overhydrate to exacerbate cerebral 
edema. •  Provide a padded cage for dogs with 
vestibular ataxia, severe dementia, or seizure

898  Blackwell’s Five-Minute Veterinary Consult  
Mactivity. •  Recumbent patients should be 
turned frequently (every 4 hours).
ACTIVITY
• Depends on severity of disease and lesion 
localization. •  Ataxic patients should be 
confined to a padded cage to avoid injury.
DIET
Ensure adequate caloric intake.
• Explain to the client that there is significant 
overlap of clinical signs among different 
inflammatory diseases. Insist on the 
importance of a diagnostic workup. 
• Mortality rate is variable but clearly biased 
by older literature describing the severe cases 
that went to post-mortem as suffering from 
GME. Brain biopsies are rarely conducted. 
Clinical experience suggests that up to 70% 
of patients can respond to therapy, especially 
if initiated early in the course of the disease. 
However, treatment may be prolonged or 
could be required for life. •  Corticosteroid 
therapy may be necessary indefinitely.
• Dexamethasone 0.2 mg/kg IV or PO q24h 
for 4 days followed by prednisone 0.5–1.0 mg/
kg PO q24h for 2 weeks. Dose is adjusted 
according to response and side effects. The goal 
is to find dosage that keeps the clinical signs 
controlled with minimal side effects. If 
deterioration of clinical signs noted when 
tapering steroids, immediately go back to 
previous dose that controlled the signs or 
consider adding other immunosuppressant 
listed below. •  To prevent gastrointestinal 
ulceration, combine steroid therapy with 
omeprazole 0.5 mg/kg PO q24h, famotidine 
0.5–1 mg/kg IV or PO q12h. •  Azathioprine 2 
mg/kg PO q24h can be added if the patient is 
not tolerating the steroids well, to allow 
reduction of the prednisone dose. Usually, the 
dose of azathioprine is reduced to 1 mg/kg PO 
q 24 after 7 days of initiating the medication. 
• Cytosine arabinoside 100 mg/m2 body 
surface area as a CRI over 12 hours. 
Alternatively 6 doses of cytosine arabinoside 
can be given q12h via SC injection. Repeat 
treatment every 3 weeks to 8 weeks pending 
clinical response. •  Mycophenolate mofetil has 
been recently advocated at a dose of 7–20 mg/
kg PO q12h for 3–4 weeks, then 10 mg/kg 
q24h. This medication can cause vomiting and 
diarrhea. •  If there is seizure activity—
phenobarbital 2 mg/kg PO q12h, levetiracetam 
20–30 mg/kg PO (ideally q8h but may be 
attempted q12h), or zonisamide 5–10 mg/kg 
PO q12h. •  Gabapentin 2–5 mg/kg PO 
q8–12h if compulsive circling is present.CONTRAINDICATIONS
• Fungal, bacterial, and protozoal conditions 
can be exacerbated by the use of steroids. It is 
important to rule out these infectious 
disorders with proper diagnostic workup. 
• Steroid should not be used in a patient 
treated or recently treated with nonsteroidal 
Reduction in corticosteroid therapy can result 
in recrudescence of clinical signs that may not 
be controlled again as initially.
• Cyclosporine 3–7 mg/kg PO q12h. 
• Leflunomide 4 mg/kg PO q24h.
  FOLLOW-UP
• Repeat neurologic examination periodically 
(every 2–4 weeks). •  Evaluate CBC and 
biochemical profile regularly to monitor for 
leukopenia, thrombocytopenia, and liver and 
kidney function if alternative drugs are used. 
• Monitor urine in patients on long-term 
steroid treatment—proteinuria or infection 
are frequent consequences. Patients receiving 
zonisamide may be at risk for keratoconjunc-
tivitis sicca and immune-mediated condi-
tions—hemolytic anemia, immune 
thrombocytopenia, and polyarthritis.
• Deterioration of clinical signs despite 
aggressive treatment. •  Status epilepticus, 
dementia, brain herniation, and death.
• Not all patients with CNS inflammatory 
disease have a poor prognosis. •  GME has 
been stereotyped as fatal without enough 
evidence. Uncertain if surviving dogs had 
GME as brain biopsies are rarely done.
Corticosteroid therapy can affect gestation.
SYNONYMS
• Granulomatous encephalitis. 
• Granulomatous meningoencephalitis. 
• Meningoencephalitis of unknown etiology. 
• Meningomyelitis. •  Encephalitis. •  Myelitis.
SEE ALSO
• Encephalitis. •  Encephalitis Secondary to 
Parasitic Migration. •  Meningitis/
Meningoencephalitis/Meningomyelitis, 
Bacterial. •  Meningoencephalomyelitis, 
Eosinophilic. •  Necrotizing Encephalitis. • Steroid-Responsive Meningitis–Arteritis— 
Dogs.
• COMS = caudo-occipital malformation 
syndrome. •  GME = granulomatous 
meningoencephalomyelitis. •  MUE = 
etiology. •  MUO = meningoencephalomyelitis 
of unknown origin. •  NSAID = nonsteroidal 
anti-inflammatory drug.
• http://www.ivis.org •  http://www.vin.com
Adamo PF , Rylaner H, Adams WM. 
Cyclosporine use in multi-drug therapy for 
etiology in dogs. J Small Anim Pract 2007, 
48(9):486–496.
Demierre S, Tipold A, Griot-Wenk ME, et al. 
Correlation between the clinical course of 
in dogs and the extent of mast cell 
infiltration. Vet Record 2001, 
148:467–472.
Granger N, Smith PM, Jeffery ND. Clinical 
findings and treatment of non-infectious 
meningoencephalomyelitis in dogs: a 
systematic review of 457 published cases 
from 1962 to 2008. Vet J 2010, 
184(3):290–297.
Lowrie M, Thomson S, Smith P , Garosi L. 
Effect of a constant rate infusion of cytosine 
arabinoside on mortality in dogs with 
meningoencephalitis of unknown origin. 
Vet J 2016, 213:1–5.
Smith PM, Stalin CE, Shaw D, et al. 
Comparison of two regimens for the 
treatment of meningoencephalomyelitis of 
unknown etiology. J Vet Intern Med 2009, 
23(3):520–526.
Talarico LR, Schatzberg SJ. Idiopathic 
granulomatous and necrotizing 
inflammatory disorders of the canine central 
nervous system: a review and future 
perspectives. J Small Anim Pract 2010, 
51(3):138–149.
Woolcock AD, Wang A, Haley A, et al. 
T reatment of canine meningoencephalomyelitis 
of unknown aetiology with mycophenolate 
mofetil and corticosteroids: 25 cases (2007–
2012). Vet Med Sci 2016, 10(2):125–135.
Author  Carolina Duque
available onlineMeningoencephalomyelitis of Unknown Etiology (MUE)  (continued)

Canine and Feline, Seventh Edition  899
MMesothelioma
  BASICS
OVERVIEW
• Rare tumor in dogs and cats arising from 
the mesothelial cells of the serosal lining of 
the pleural, pericardial, or peritoneal 
cavities.
• Also has been reported in dogs to arise from 
the tunica vaginalis of the testes.
• Older animals—dog and cat.
• Sclerosing subtype more common in males.
• German shepherd dogs overrepresented.
SIGNS
• Pleural effusion—dyspnea, tachypnea, 
exercise intolerance, coughing, gagging, 
cyanosis.
• Pericardial effusion—lethargy, anorexia, 
weakness, collapse, respiratory distress, 
exercise intolerance, distended abdomen, 
vomiting.
• Ascites—distended abdomen, anorexia, 
vomiting, lethargy, abdominal discomfort.
• Swollen testes.
• Sclerosing subtype signs are secondary to 
restriction around affected organs—vomiting, 
urinary issues.
• Increased risk with asbestos exposure.
• Possible increased risk in golden retrievers with 
idiopathic hemorrhagic pericardial effusion.
  DIAGNOSIS
Other causes of effusions—hypoproteinemia, 
vasculitis, neoplasia (e.g., lymphoma, 
chemodectomas, hemangiosarcoma, 
carcinomatosis), idiopathic, congestive heart 
failure, liver disease, infectious/inflammatory.
N/A
IMAGING
• Thoracic radiography—identification of 
pleural effusion, evaluation of cardiac 
silhouette (i.e., globoid heart consistent with 
pericardial effusion).
• Echocardiography—identification of 
pericardial effusion; rule out primary cardiac 
• Thoracic and abdominal ultrasonography—
evaluation of effusions.
• CT—identification of mass lesions and 
evaluation of lungs in the face of pleural effusion.
• Cytology of effusions to rule out infectious 
causes or lymphoma—difficult to diagnose 
mesothelioma on cytology as mesothelial cells are typically shed into effusions and can be 
highly reactive.
• Exploratory surgery (open or via thoraco  scopic 
or laparoscopic examination) with biopsies.
• Fibronectin levels in effusions—not specific 
for mesothelioma but typically elevated in 
neoplastic effusions.
  TREATMENT
• Pericardiectomy or mass removal if possible.
• Symptomatic pericardiocentesis or 
thoracocentesis.
• Intracavitary chemotherapy:
◦ Cisplatin (dog only) 50–70 mg/m2 every 
3 weeks with saline diuresis.
◦ Carboplatin (cat) 180–200 mg/m2 every 
3–4 weeks.
◦ Carboplatin (dog) 300 mg/m2 every 3 weeks.
◦ Mitoxantrone (dog) 5.0–5.5 mg/m2 every 
3 weeks.
• IV chemotherapy—doxorubicin 30 mg/m2 
(dog >10 kg) or 1 mg/kg (dog <10 kg or cat), 
or mitoxantrone (4.5–5.5 mg/m2 dog and 
cat) once every 3 weeks.
• Chemotherapy can cause gastrointestinal, 
seek advice if unfamiliar with cytotoxic drugs.
• Cisplatin in particular is nephrotoxic. Do 
not use in cats; causes fatal pulmonary edema.
  FOLLOW-UP
• Blood tests—especially CBC to monitor for 
bone marrow suppression secondary to 
chemotherapy and renal values to monitor for 
renal toxicity if treating with cisplatin.
• Serial thoracic radiography and/or ultra­
sounds of heart, thoracic cavity, or abdominal 
cavity to monitor for recurrence of effusions 
and to monitor tumor response.
• Prognosis—variable and anecdotal:
◦ Intracavitary cisplatin (dogs)—range 8 
months to >3 years.
◦ Intracavitary carboplatin (cats) with 
piroxicam—6 months.
◦ Surgery and intracavitary cisplatin and 
IV doxorubicin—>27 months.
◦ Reported survival with surgery alone—
4–9 months.  MISCELLANEOUS
Garrett LD. Mesothelioma. In: Withrow SJ, 
Vail DM, Page RL, eds., Small Animal 
Clinical Oncology, 5th ed. Philadelphia, 
PA: Saunders, 2013, pp. 696–700.

M900  Blackwell’s Five-Minute Veterinary Consult  
MMetabolic, Nutritional, and Endocrine Bone Disorders
  BASICS
• Osteochoendrodysplasia, osteogenesis 
imperfecta (OI), and growth hormone  
(GH) anomalies include many metabolic, 
nutritional, and endocrine bone disorders. 
• Osteochondrodysplasia (OCDP) is a 
growth and developmental abnormality 
resulting in the lack of normal bone growth 
and bone deformities. •  OI is a hereditary 
disease characterized by extremely fragile 
bones and teeth caused by defects in the 
structure of type I collagen. •  GH anomalies 
include, among others: ◦ Acromegaly (ACM)—  
results from excessive pituitary GH 
production or excessive production of female 
sex GH. ◦ Dwarfism (DW)—results from 
congenital lack of pituitary GH production.
• OCDP—genetic defect affecting all 
cartilage in the entire body. •  OI—genetic 
defect of type I collagen formation. Type I 
collagen is the most abundant structural 
component of skin, bone, cartilage, tendons, 
and ligaments. •  ACM—endogenous 
progesterone or exogenous progestins may 
give rise to GH hypersecretion of mammary 
origin. Mammary-derived (with or without 
mammary tumors) GH is biochemically 
identical to pituitary GH. Pituitary adenoma-
related increased progesterone production is 
also possible. Hypothyroidism can also lead 
to ACM. •  DW—congenital GH deficiency.
• Cardiovascular. •  Endocrine/metabolic. 
• Musculoskeletal. •  Respiratory. •  Skin/
exocrine.
GENETICS
• OCDP—autosomal dominant inheritance. 
• OI—autosomal recessive; collagen type 
I-encoding genes COL1A1  and COL1A2  are 
affected. •  ACM—abnormalities in the 
anterior pituitary gland; inherited in the Saint 
Bernard. •  DW—autosomal recessive 
All conditions discussed are rare.
N/A
Species
• OCDP , ACM—dog and cat. •  OI—dog; 
rare in cat. •  DW—dog.
• OCPD—Scottish fold cat; great Pyrenees, 
Alaskan Malamute, Samoyed, Scottish 
deerhound, Labrador retriever, basset hound, and Norwegian elkhound. •  OI—golden 
retriever, collie, poodle, beagle, Bedlington 
terrier, wirehaired dachshund, Norwegian 
elkhound; domestic shorthair cats. •  ACM—
Saint Bernard, cats. •  DW—German 
• OCDP—immature animals. •  OI—3–18 
weeks. •  ACM—middle-aged to elderly 
females. •  DW—2–5 months.
• OCPD—N/A. •  OI—N/A. •  ACM—
dogs: female; cats: male or female.
SIGNS
• OCDP—short, thickened, and hard, 
movable tail; short, buckled legs. Severity of 
the clinical signs most likely influenced by 
level of expression of dominant gene carrier of 
the mutation (homo- or heterozygous). 
• OI—signs range from perinatal death to 
mild bone fragility, severe bone deformity, 
and innumerable fractures following minor 
trauma. •  ACM—soft tissue swelling of the 
face and abdomen; severe hypertrophy of soft 
tissues of the mouth, tongue, and pharynx 
(latter may cause stridor); polyuria; occasion-
ally polyphagia. •  DW—proportionate 
growth retardation and an abnormally soft 
and woolly hair coat without guard hair.
Signs frequently reported by the owner:
• OCDP—difficult and decreased mobility, 
jumping, climbing, lameness; signs 
progressing. •  OI—sudden onset or 
progressive lameness. •  ACM, DW—similar 
to physical examination findings.
• OCDP: ◦ Cats—pain of long bones; 
unwillingness to rise. ◦ Dogs—larger than 
normal head, shorter jaw and resulting 
malaligned teeth, shortened bones, joint 
enlargement, lateral deviation of thoracic limbs, 
spinal deviation to either side. •  OI—pain and 
lameness secondary to fractures. Dentinogenesis 
imperfecta (secondary to abnormal collagen I) 
can be noted in addition to or as single entity: 
severe thinning of the dentine layer, leading to a 
translucent appearance, pink discoloration, and 
multiple tooth fractures. Sudden death due to 
rupture of chordae tendineae (also affected by 
abnormal cartilage), has been reported. 
• ACM—inspiratory stridor, thick skin folds 
(mainly neck), prognathism, wide interdental 
spaces. Visceromegaly, if generalized, can result 
in abdominal enlargement. •  DW—profound 
dwarfism, retention of puppy hairs, lack of 
guard hairs. Hairs can be epilated easily. 
Gradual progressive truncal alopecia can be 
noted. Progressive dermal hyperpigmentation, 
scaly skin, and dermatitis is possible. In males, 
cryptorchidism is common; in females, 
persistent estrus is frequent. Continuous heart murmur secondary to a patent ductus arteriosus 
has been reported.
CAUSES
N/A for any discussed diseases; except ACM 
if exogenous progesterone is administered.
  DIAGNOSIS
• OCDP , OI—metabolic disease, physical 
abuse, alimentary secondary hyperpara -
thyroidism, hypovitaminosis D, hypothyroidism. 
• ACM—Pituitary gland tumor; long-term use 
of progesterone (older dogs, infertile bitches, 
aggressive dogs). •  DW—malnutrition.
• The following should be specifically 
evaluated for all discussed diseases: serum 
concentrations of ionized calcium, phosphorus, 
vitamin D, and parathormone. •  OCDP , OI, 
DW—N/A. •  ACM—hyperglycemia, 
hyperphosphatemia, hypercholesterolemia, 
hyperproteinemia, increases in liver enzymes 
(specifically elevated alkaline phosphate), 
decreased thyroid hormone. •  DW—elevated 
plasma creatinine concentration.
• OCDP , OI—N/A. •  ACM—prolactin, 
cortisol, basal plasma GH levels elevated with 
disease progression. Elevated plasma insulin-like 
growth factor I (IGF-I) levels (however, increased 
GH and IGF can also be seen in healthy 
animals). Free thyroxine, thyroid-stimulating 
hormone (TSH), and adrenocorticotropic 
hormone (ACTH) stimulation tests 
recommended. GH test recommended to 
evaluate the pituitary gland function. Follicle-
stimulating hormone (FSH) and luteinizing 
hormone (LH) tests are recommended. Diabetes 
mellitus has been reported to develop secondary 
to insulin resistance, thus urinalysis with ACM 
can reveal glucosuria. •  DW—basal plasma 
concentrations of GH and IGF-I, prolactin, 
thyrotropin, and LH are low. With combined 
anterior pituitary function test, often no response 
of GH, TSH, and prolactin, but minor response 
of LH and FSH.
IMAGING
• OCDP—radiographic changes more 
prominent in pelvic limbs (size and shape of 
the tarsal, carpal, metatarsal, metacarpal 
bones, phalanges), sacrum (articular spaces 
decreased), exostoses with diffuse osteopenia, 
zones of rarefication. Spine may show 
scoliosis, lordosis, or kyphosis. •  OI—radio -
graphs reveal less opaque than normal long 
bone cortices, frequently pathologic fractures 
or evidence of chronic healing fractures.

Canine and Feline, Seventh Edition  901
MM• ACM—radiographs of thorax (in case of 
mammary tumor metastasis; also 85% 
cardiomegaly reported in cats); MRI of brain 
(pituitary); ultrasound of abdomen (assess 
organomegaly—specifically liver and kidneys). 
• DW—MRI (brain), echocardiography.
• OCDP—bone histology. •  OI—analysis of 
type I collagen obtained from cultured skin 
fibroblasts. •  ACM/DW—N/A.
• OCDP , DW—N/A. •  OI—bone: absence 
of secondary spongiosa, irregular woven bone 
with absence of Haversian canals. •  ACM—
pituitary or mammary gland changes depend 
on tumor. •  DW—aplasia of the hypophysis/
pituitary gland.
  TREATMENT
N/A
ACTIVITY
• OCDP , OI—decrease activity to reduce 
discomfort. •  ACM—N/A. Rest 3 weeks if 
surgery (ovariohysterectomy) done. Specific 
care based on specialist’s recommendation 
following pituitary gland radiation. 
• DW—N/A.
DIET
OCDP , OI, ACM, DW—healthy diet.
• OCDP , OI—N/A; no cure. •  ACM, 
DW—N/A.
• OCDP—N/A; corrective osteotomies are not 
rewarding. •  OI—surgical treatment of 
fractures. •  ACM—withdrawal of exogenous 
progestagens and/or ovario(hyster)ectomy. If 
pituitary, consider hypophysectomy. Radiation 
of the hypophysis can also be considered.
• DW—N/A.
• OCDP—dogs: nonsteroidal anti-
inflammatory drugs (NSAIDs); cats: 
robenacoxib 1 mg/kg PO once a day for 3 
days. •  OI—vitamin C 75 mg/kg PO once a 
day; bisphosphonate supplementation 
(alendronate sodium): dogs: 0.5–1 mg/kg PO 
once a day on empty stomach; cats: 10 mg/
cat PO on empty stomach once a week. Note: 
effectiveness of bisphosphonates to treat OI 
in dogs and cats has not been evaluated. 
• ACM: ◦ If progestagen-induced—aglepristone (progesterone-receptor blocker) 15 
mg/kg SQ on 2 consecutive days, repeat weekly 
until effect of progestagen ceases; surgery (see 
Surgical Considerations). ◦ If hypothyroidism-
induced—levothyroxine sodium 0.02 mg/kg 
(dog) or 0.01 mg/kg (cat) PO once a day. 
Adjust dose based on the serum total thyroxine 
concentrations 4–6 hours post tablet admini -
stration, along with clinical response. •  DW—
porcine GH 0.1–0.3 IU/kg SQ, 3 times a 
week. Thyroid hormone replacement if 
evidence of secondary hypothyroidism (see 
ACM dosing recommendation above).
N/A
• OCDP , OI—N/A. If NSAIDs are used, 
monitor for possible side effects as listed in 
package inserts. •  ACM—N/A.
• OCDP—must not use other NSAIDs. 
• OI—none. •  ACM—theoretically, the 
following interactions may occur with 
aglepristone: efficacy of glucocorticoids and 
progestins might be reduced. Manufacturer 
states that despite lack of data, the following 
medications may interact with aglepristone: 
ketoconazole, itraconazole, erythromycin. Drug 
interactions when using levothyroxine sodium 
can include: amiodarone, antidepressants, 
antidiabetics, cholestyramine, corticosteroids, 
digoxin, ferrous sulfate, ketamine, phenobarbital, 
propylthiouracil, rifampin, sertraline, sucralfate, 
sympathicomimetic agents, warfarin.
• OCDP , OI—N/A. •  ACM—aglepristone; 
may be difficult to obtain in the United 
States.
  FOLLOW-UP
• OCDP—2 weeks, then as needed. Note 
that osteoarthritis can develop long term. 
• OI—4–8 weeks for bone healing and 
improvement of bone density. •  ACM—
initially weekly, then every month to monitor 
until stable. •  DW—weekly.
N/A
• OCDP , DW—N/A. •  OI—other fractures. 
• ACM—if tumorous cause, metastasis and 
worsening of disease.
• OCDP—recurrence of signs and discom-
fort from arthritis. •  OI—development of 
other fractures. •  ACM—regression of 
clinical signs over time is expected; if GH did not completely exhaust pancreatic beta cells, 
diabetes mellitus might resolve. •  DW—sig-
nificant increase in body size often not seen 
(due to closure of epiphyseal plates); growth 
of primary hair is expected, while growth of 
guard hairs is variable.
• OCDP—N/A. •  OI—can be accompanied 
by blue sclera, hearing loss, dwarfism, 
pulmonary pathology. •  ACM—diabetes 
mellitus, cardiac disease, decreased hepatic 
and renal function, peripheral neuropathies. 
• DW—secondary bacterial dermatitis. Due 
to combined pituitary hormone deficiency, 
secondary hypothyroidism is frequent. GH 
administration might result in development 
of diabetes mellitus.
Affected animals for all discussed topics are 
not to be used for breeding. To treat ACM, 
ovario(hyster)ectomy is often needed.
• ACM = acromegaly. •  ACTH = 
adrenocorticotropic hormone. •  DW = 
dwarfism. •  FSH = follicle-stimulating 
hormone. •  GH = growth hormone. •  IGF = 
insulin-like growth factor. •  LH = luteinizing 
hormone. •  OCDP = osteochondrodysplasia. 
• OI = osteogenesis imperfecta. •  TSH = 
Hazewinkel HAW. Metabolic, nutritional, 
and endocrine bone disorders. In: Bojrab 
MJ, Monnet E, eds., Mechanisms of 
Disease in Small Animal Surgery, 3rd ed. 
Jackson, WY: Teton NewMedia, 2010, pp. 
601–610.
Kooistra H.S. Acromegaly in dogs. In: Rand 
J., ed., Clinical Endocrinology of 
Companion Animals. Hoboken, NJ: 
Wiley-Blackwell, 2014, pp. 421–426.
Montgomery R. Miscellaneous orthopedic 
diseases. In: Bojrab MJ, Monnet E., eds., 
Mechanisms of Disease in Small Animal 
Surgery, 3rd ed. Jackson, WY: Teton 
NewMedia, 2010, pp. 590–600.
Seeliger F , Leeb T, Peters M, et al. 
Osteogenesis imperfecta in two litters of 
dachshunds. Vet Pathol 2003, 40:530–539.
Von Pfeil DJF , DeCamp CE, Abood SK. The 
epiphyseal plate: nutritional and hormonal 
influences; hereditary and other disorders. 
Compend Contin Educ Vet 2009, 
31(7):E1–E14.
Author  Dirsko J.F . von Pfeil
Consulting Editor  Mathieu M. Glassman(continued)  Metabolic, Nutritional, and Endocrine Bone Disorders

902  Blackwell’s Five-Minute Veterinary Consult  
MMetaldehyde Toxicosis
  BASICS
OVERVIEW
• Form of acetaldehyde; primarily affects the 
• Mainly found in slug and snail baits; 
sometimes in solid fuel for camp stoves.
• Crosses the blood–brain barrier and 
disrupts GABAergic inhibitory action, 
facilitating neuronal excitation and increasing 
potential for convulsions.
• Systems affected include: neuromuscular 
(seizures and muscle tremors), hepatobiliary 
(delayed hepatotoxicosis reported in dogs 
only), and multiple organ failure (secondary 
to seizures and hyperthermia).
• Incidence/prevalence—depends on presence 
and accessibility; weather resistant: persists in 
the environment for >14 days.
• More frequent in coastal, low-lying, 
temperate and subtropical regions of United 
States. Snails and slugs are common pests in 
those locations.
Species
Dogs; much less often in cats.
SIGNS
• Generally, within 3-4 hours but may occur 
in <30 minutes.
• Anxiety, panting, restlessness.
• Salivation, gastrointestinal upset.
• Tachypnea, dyspnea.
• Hyperthermia up to 108°F (42.2°C).
• Ataxia, tremors, seizures (intermittent then 
continuous).
• Mydriasis, nystagmus (especially in cats).
CAUSES
Ingestion of metaldehyde.
  DIAGNOSIS
• Toxins capable of neurologic signs—
amphetamines, bromethalin, blue-green 
algae, chocolate, hops, ivermectin, lead, 
neurotoxic mushrooms, organophosphate and 
some carbamate insecticides, pyrethroids, salt 
(ornaments, playdough), strychnine, 
tremorgenic mycotoxins, xylitol, and zinc 
phosphide.
• Nontoxic causes.
• No specific diagnostic features.
• Metabolic acidosis.• Delayed changes in hepatic or renal values 
from uncontrolled hyperthermia/seizures.
Presence in gastric contents, serum, urine, 
brain, or liver. Testing capabilities vary by lab; 
call to see what samples are recommended.
• Lesions neither consistent nor pathognomonic 
on necropsy (gross or histopathology).
• Gastric contents may have a formaldehyde 
odor.
  TREATMENT
• Appropriate health care consists of 
emergency exam, decontamination, intensive 
care until signs resolve (24–72 hours).
• Full recovery may take several weeks with 
hepatotoxicosis.
• Nursing care involves controling 
hyperthermia with cooling measures until 
reaching 103.5°F (39.7°C). Do not overcool. 
Monitor to prevent aspiration of vomitus.
• Monitor CNS status.
• Do not feed vomiting, convulsing, or 
heavily sedated patients.
• No antidote available.
• Emetics if minutes after ingestion or gastric 
lavage with intubation (preferred with large 
ingestions or symptomatic patient).
• Activated charcoal with cathartic if no 
• Crystalloids to prevent/correct dehydration 
• Seizures—benzodiazepines (first choice), 
barbiturates, levetiracetam, propofol, or 
inhalant anesthetics. Consider CRIs.
• T remors—methocarbamol 55–220 mg/kg 
IV; do not exceed 330 mg/kg/day.
• Hepatoprotectants as needed.
• Warm water enemas if toxicant seen in 
the stool.
Do not induce vomiting or give activated 
charcoal to a patient that is convulsing or 
heavily sedated.
Use depressant drugs cautiously in an already 
depressed patient, and only if other options 
are unavailable or ineffective. Use 
anticonvulsants at lowest effective doses.  FOLLOW-UP
• Periodically allow anticonvulsants to wear 
off to reevaluate seizure condition.
• Once acute phase has passed, monitor 
hepatic/renal function. Hepatic damage may 
develop 48–72 hours later. Rhabdomyolysis-
induced acute renal failure rare but possible.
• Do not apply in areas accessible to pets.
• Manufacturers may add green/blue dye to 
assist with identification. Can cause confusion 
with rodenticides.
• Added bittering agents do not reliably 
discourage ingestion. New products contain 
iron phosphate instead (less toxic).
• Liver or renal dysfunction after initial signs 
(sequelae to seizures and hyperthermia).
• Aspiration pneumonia secondary to seizures.
• Hyperthermia may lead to disseminated 
intravascular coagulation (DIC) or multiple 
organ failure.
• Good to excellent if treated early and 
aggressively.
• Guarded to poor if large ingestion or if 
treatment delayed or inadequate.
• Fatalities can be seen secondary to DIC or 
• Survival beyond the first 24 hours is 
positive prognostic indicator.
Companion Small Animal Toxicology, 2rd ed. 
Ames, IA: Wiley-Blackwell, 2016, pp. 672–677.
Peterson M, Talcott, P . Small Animal 
Toxicology, 3rd ed. St. Louis, MO: Elsevier, 
2013, pp. 635–642.
Author  Kia Benson
acknowledge the prior contribution of James 
N. Eucher.

Canine and Feline, Seventh Edition  903
MMetformin Toxicosis
  BASICS
OVERVIEW
• Metformin (Glucophage) is a biguanide 
antihyperglycemic prescription medication 
labeled for the treatment of non-insulin-
dependent (type 2) diabetes mellitus in 
humans.
• Available as single or extended release 
formulation (Glucophage XR).
• Formulated as a single ingredient and in 
combination with other antidiabetic 
• The agent potentially could be useful in the 
adjunctive treatment of non-insulin-
dependent diabetes mellitus in cats; use is 
• Toxicity causes gastrointestinal signs and 
lethargy.
• 578 exposures to metformin were reported 
to the American Society for the Prevention of 
Cruelty to Animals (ASPCA) Animal Poison 
Control Center (APCC) during 2015–2018. 
Of these, 96.1% dogs, 3.7% cats, 0.3% birds. 
Common findings recorded are vomiting 
9.3%, lethargy 3.1%, hypoglycemia 1.9%, 
trembling 1.5%, diarrhea 1.2%.
• Vomiting developed from doses as low as 
15.3 mg/kg with hypoglycemia at 48 mg/kg.
• No breed, age, or sex predilections.
SIGNS
Dogs
• Common sign—vomiting.
• Possible signs—lethargy, hypoglycemia, 
trembling and diarrhea.
Cats
• Frequent sign—vomiting.
• Possible signs—lethargy, diarrhea, and 
Ingestion of metformin in single-ingredient 
preparations as well as in combination with 
other antidiabetic agents.
  DIAGNOSIS
Other gastrointestinal tract irritants.
Azotemia reported in humans due to acute 
renal failure in cases of biguanide lactic 
acidosis; not reported in animal toxicities.
• Blood gases—lactic acidosis rare but 
possible with large ingestions (a shih tzu 
ingesting 167.2 mg/kg of metformin developed lactic acidosis, vomiting, and 
hypothermia; no hypoglycemia developed 
and the dog fully recovered with treatment).
• High-performance liquid chromatography 
may identify presence of metformin in 
plasma; drug levels are not clinically useful.
N/A
N/A
  TREATMENT
• Induce emesis within the first 2–3 hours of 
exposure.
• Activated charcoal should only be 
considered with very large exposure.
• T reat gastrointestinal signs supportively.
• T reat lactic acidosis if present.
• Metoclopramide 0.2–0.5 mg/kg PO, SC, or 
IM q6h.
• Sucralfate 0.5–1 g PO q8–12h for dogs and 
0.25–0.5 g PO q8–12h for cats.
• Famotidine 0.5–1.1 mg/kg orally q12–24h 
for dogs and cats.
• Ranitidine 1–2 mg/kg PO, SC, or IM 
q8–12h for dogs and 2.5 mg/kg IV q12h or 
3.5 mg/kg PO q12h for cats.
• Omeprazole 0.5–1 mg/kg PO q24h for 
• Bicarbonate—if serum bicarbonate or total 
CO2 is unavailable: 2–3 mEq/kg IV over 30 
minutes if patient has decreased tissue 
perfusion or renal failure and does not have 
diabetic ketoacidosis. Must be used judiciously.
• Concurrent administration of cimetidine 
may reduce the urinary excretion of 
metformin by competing for renal tubular 
organic cationic transport systems.
• The manufacturer states that other cationic 
drugs that undergo substantial tubular 
secretion (e.g., amiloride, digoxin, morphine, 
procainamide, quinidine, quinine, ranitidine, 
triamterene, trimethoprim, and vancomycin) 
may possibly decrease the urinary excretion of 
metformin.
  FOLLOW-UP
Good prognosis assuming lactic acidosis does 
not occur.
N/A
• No evidence of harm to the fetus or 
impaired fertility during reproduction studies 
in rats and rabbits given metformin 
hydrochloride dosages of 600 mg/kg daily.
• No adequate and controlled studies to date 
using metformin hydrochloride in pregnant 
women.
• Excreted in milk in levels similar to plasma. 
Caution advised in lactating queens.
SEE ALSO
• APCC = Animal Poison Control Center.
• ASPCA = American Society for the 
Prevention of Cruelty to Animals.
• http://chem.sis.nlm.nih.gov/chemidplus/
rn/657-24-9
• http://www.aspcapro.org/search/index/
METFORMIN
Heller JB. Metformin overdose in dogs and 
cats. Vet Med 2007, 231–234.
Plumb DC. Metformin. In: Plumb DC, ed., 
Veterinary Drug Handbook, 8th ed. Ames, 
IA: Wiley-Blackwell, 2018, pp. 762–763.
Author  Hany Youssef

904  Blackwell’s Five-Minute Veterinary Consult  
MMethemoglobinemia
  BASICS
• Methemoglobin content in blood >1.5% of 
total hemoglobin.
• Methemoglobin differs from hemoglobin in 
that the iron moiety of heme groups has been 
oxidized from the ferrous (2+) to the ferric 
(3+) state.
• About 3% of hemoglobin is oxidized to 
methemoglobin each day in normal animals 
as a result of autoxidation of hemoglobin or 
secondary to oxidants produced in normal 
metabolic reactions.
• Methemoglobin usually accounts for <1% 
of total hemoglobin, because it is constantly 
reduced back to hemoglobin by an NADH-
dependent cytochrome b5 reductase 
 (methemoglobin reductase) enzyme reaction 
within red blood cells (RBCs).
• Caused by either increased production of 
methemoglobin by oxidants or decreased 
reduction of methemoglobin associated with 
a deficiency of the RBC cytochrome b5 
reductase enzyme or defective cytochrome b5.
• Hemic/lymphatic/immune—reduced 
oxygen-carrying capacity of blood, because 
methemoglobin cannot bind oxygen; if 
methemoglobin content reaches high values 
(e.g., >50% of total hemoglobin), organs may 
suffer hypoxic injury.
• Hepatobiliary—in addition to hypoxic 
injury, the liver may be damaged directly by 
oxidant drugs that it metabolizes.
• Renal/urologic—in addition to hypoxic 
injury, the kidneys may be damaged if 
intravascular hemolysis occurs (pigmentary 
nephropathy).
• Deficiency in RBC cytochrome b5 reductase 
has been recognized in the Chihuahua, borzoi, 
English setter, mixed-breed dog, coonhound, 
poodle, corgi, Pomeranian, Staffordshire bull 
terrier, Parson Russell terrier, Australian shepherd 
dog, and American Eskimo dog, and in domestic 
shorthair cats. A defect in cytochrome b5 has 
been described in a mixed-breed dog.
SIGNS
Caused Directly
• Possibly none in animals with mild to 
moderate methemoglobinemia.
• Cyanotic-appearing mucous membranes—
may be difficult to recognize in heavily 
pigmented animals.
• Lethargy, tachycardia, tachypnea, ataxia, 
and stupor caused by hypoxemia when 
methemoglobin content exceeds 50%.• Coma-like state and death when 
methemoglobin content reaches 80%.
Caused by Associated Diseases
• Vomiting, anorexia, and diarrhea possible 
in patients with drug toxicity.
• Hemoglobinuria secondary to severe 
intravascular hemolysis in some patients with 
Heinz body hemolytic anemia.
• Subcutaneous edema, especially involving 
the face, and salivation in animals with 
acetaminophen toxicity.
CAUSES
• Toxicity—acetaminophen, benzocaine, 
phenazopyridine, and skunk musk cause 
Heinz body hemolytic anemia; excess nitrite 
in pet food and hydroxycarbamide toxicity 
are reported to cause methemoglobinemia 
without Heinz body hemolytic anemia.
or a defect in RBC cytochrome b5.
• Application of benzocaine or prilocaine to 
traumatized skin or mucous membranes 
increases the likelihood of systemic 
absorption and methemoglobinemia.
• Cats are much more likely to develop 
clinically significant methemoglobinemia than 
are dogs after acetaminophen administration; 
this drug is not recommended for use in cats.
• Methemoglobinemia secondary to cyto -
chrome b5 reductase deficiency and a defect in 
cytochrome b are inherited disorders.
  DIAGNOSIS
• Both low blood oxygen tension and 
methemoglobinemia can cause cyanotic-
appearing mucous membranes and dark-
colored blood samples; hypoxemia is 
documented by measuring PaO2 <80 mmHg 
in an arterial blood sample, or an SpO2 <95% 
measured via pulse oximetry.
• Methemoglobinemia is suspected when 
arterial blood with normal or high PO2 is 
dark colored.
Drugs That Alter Laboratory Results
None
Results
Hemolysis in the sample may raise the 
methemoglobin value, especially if the 
methemoglobin assay is not conducted soon 
after sample collection.
• Valid, as long as the method to lyse RBCs 
does not cause methemoglobin formation in 
the animal being tested.• Saponin should not be used to lyse RBCs, 
because it raises the methemoglobin value in 
some species.
• Chronic methemoglobinemia secondary to 
cytochrome b5 reductase deficiency can result 
in an elevated hematocrit (HCT); in contrast, 
hemolytic anemia may accompany methemo-
globinemia caused by oxidant drugs.
• If severe or induced by oxidant drugs, 
evidence of injury to various organs (e.g., 
high serum creatinine concentration or 
alanine aminotransferase [ALT] activity) may 
be seen.
• Spot test—determine if the patient’s 
methemoglobin content is clinically 
important: one drop of blood from the 
patient is placed on a piece of absorbent white 
paper and a drop of normal control blood is 
placed next to it. If the methemoglobin 
content is ≥10%, the patient’s blood will be 
noticeably browner than the bright red of the 
control blood.
• Co-oximetry is the method of choice for 
accurate measurement of methemoglobin 
content in whole blood samples.
• Methemoglobin content in dogs with 
cytochrome b5 reductase deficiency reportedly 
varies from 13 to 51%; the methemoglobin 
content in six deficient cats ranged from 44 
to 52%.
• A definitive diagnosis of cytochrome b5 
reductase deficiency is made by measuring 
enzyme activity in RBCs; this assay is done in 
a few research laboratories and requires that 
arrangements be made before blood samples 
are submitted. Genetic testing may become 
available now that mutations have been 
documented in the cytochrome b5 reductase 
gene ( CYB5R3 ) in dogs and a cat. Genetic 
testing is required to diagnose a cytochrome 
b5 defect.
IMAGING
N/A
• Blood smears should be stained with 
methylene blue for detection of Heinz 
bodies.
• The presence of Heinz bodies indicates 
exposure to an oxidant drug that may also 
cause hemolytic anemia.
  TREATMENT
• Mild to moderate—does not require 
specific treatment to reduce the methemo-
globin content.
• Drug-induced—the use of the drug should 
be discontinued; RBCs can convert much of 
the methemoglobin back to hemoglobin

Canine and Feline, Seventh Edition  905
Mwithin 24 hours after elimination of drug 
exposure.
• Inherited cytochrome b5 reductase 
deficiency—animals have normal life 
expectancy and generally do not require 
treatment, although veterinarians may wish to 
give a single IV injection of methylene blue 
1 hour before a deficient animal is anesthetized 
for surgery to maximize the amount of 
hemoglobin that is capable of binding oxygen.
• Whole blood or packed RBC transfusions 
should be given to patients with severe 
anemia and those with rapidly decreasing 
HCT and clinical signs suggesting a 
• Severe intravascular hemolysis—IV fluid 
administration recommended in addition to 
blood products.
• T reatment of electrolyte or acid–base 
imbalances may also be indicated in patients 
with severe vomiting or diarrhea, concomitant 
renal injury, or shock.
• Administration of oxygen is of limited value 
because methemoglobin cannot bind oxygen, 
and an increase in dissolved oxygen results in 
only a small increase in blood oxygen content.
• Methylene blue—given slowly over several 
minutes as a 1% solution (1 mg/kg IV), may be 
administered in patients with severe methemo -
globinemia; a dramatic response should occur 
during the first 30 minutes of treatment.
• N-Acetylcysteine is efficacious in the 
treatment of acetaminophen toxicity if given 
within a few hours after exposure; recommended dosage is 140 mg/kg PO, IV 
followed by 70 mg/kg PO, IV q6h for seven 
None
Methylene blue treatment can potentiate the 
formation of Heinz bodies and cause anemia. 
In patients that have been given drugs that 
cause substantial Heinz body formation, it is 
prudent to measure the HCT for 3 days after 
methylene blue treatment to ensure that 
clinically important anemia does not develop.
Methylene blue treatment will interfere with 
monitoring of Spo2 by pulse oximetry.
None
  FOLLOW-UP
• The cyanotic appearance of skin and 
mucous membranes should disappear after 
reduction of methemoglobin to an amount 
that does not produce clinical signs.
• Blood on the spot test should appear bright 
red after reduction of methemoglobin to 
values <10% of total hemoglobin.
• HCT should be monitored in patients with 
Heinz body anemia or following methylene 
blue administration for at least 3 days after 
initial exposure.
Coma and death can occur if methemoglobin 
content reaches 80% of total hemoglobin.  MISCELLANEOUS
Heinz body anemia.
None
SEE ALSO
 Suggested Readings
Harvey JW. Veterinary Hematology. 
A Diagnostic Guide and Color Atlas. 
St. Louis, MO: Elsevier Saunders, 2012, 
pp. 12–13, 96–97.
Jaffe JA, Harmon MR, Villani NA, et al. 
Long-term treatment with methylene blue in 
a dog with hereditary methemoglobinemia 
caused by cytochrome b5 reductase deficiency. 
J Vet Intern Med 2017, 31:1860–1865.
McKenna JA, Sacco J, Son TT, et al. Congenital 
methemoglobinemia in a dog with a promoter 
deletion and a nonsynonymous coding variant 
in the gene encoding cytochrome b5. J Vet 
Intern Med 2014, 28:1626–1631.
Tani A, Yamazaki J, Nakamura K, et al. 
Congenital methemoglobinemia in a cat with 
reduced NADH-cytochrome b5 reductase 3 
activity and missense mutations in CYB5R3. 
Jpn J Vet Res 2017, 65:201–206.
Consulting Editor  Melinda S. Camus(continued)  Methemoglobinemia

906  Blackwell’s Five-Minute Veterinary Consult  
MMetritis
  BASICS
OVERVIEW
• Bacterial uterine infection that develops in 
the immediate postpartum period (usually 
within the first week); occasionally develops 
after an abortion or nonsterile artificial 
insemination—rarely after natural breeding.
• Bacteria—ascend through the open cervix 
to the uterus; postpartum uterus provides an 
ideal environment for growth; Gram-negative 
bacteria (e.g., Escherichia coli ) commonly 
isolated.
lead to septic shock.
• Can become chronic and lead to infertility.
• No age or breed predilection.
SIGNS
• Malodorous, purulent, sanguinopurulent, 
or dark green vulvar discharge.
• Neglect of puppies and kittens.
• Reduced milk production.
• Fever.
• Large uterus on abdominal palpation.
• Injected mucous membranes (septic shock).
• Tachycardia, hypotension, other signs of 
shock.
• Dystocia.
• Obstetric manipulation.
• Retained fetuses or placentas.
• Prolonged delivery (large litter).
• Post abortion, and post natural or artificial 
insemination (rare).
  DIAGNOSIS
• Subinvolution of placental sites—no sign of 
infection on cytologic examination of vagina.
• Eclampsia—differentiated by serum 
calcium concentration.
• Neutrophilia with left shift, although 
neutropenia and leukopenia are occasionally 
seen, especially in patients with septic shock.
• High packed cell volume and total plasma 
protein concentration; azotemia secondary to dehydration/hypovolemia. Normocytic, 
also occur.
• With endotoxemia or sepsis, hypoalbu-
minemia, elevation of C-reactive protein 
concentration, and other acute phase changes 
may occur. Elevated liver enzyme activities 
• Urine specific gravity may be elevated (from 
dehydration) or decreased (isosthenuria).
• Urinalysis (obtain via ultrasound-guided 
cystocentesis) may reveal bacteriuria.
N/A
IMAGING
• Radiography—reveals a large uterus and 
possibly retained fetus(es).
• Ultrasonography—intrauterine fluid 
accumulation and increased horn width, 
retained placenta(s), and retained fetus(es); 
abdominal effusion may be present if uterine 
rupture.
• Vaginal cytologic examination—detect 
degenerative neutrophils with intracellular 
bacteria.
• Guarded anterior vaginal or transcervical 
culture—aerobes and anaerobes; culture and 
sensitivity recommended.
  TREATMENT
• Inpatient until systemic signs resolve.
• T reat shock—IV balanced electrolyte 
solution.
• Correct electrolyte imbalances and 
• Ovariohysterectomy—treatment of choice 
for uterine rupture or severe sepsis, and if 
future breeding is not desired; the uterus is 
friable; pack off and handle gently at surgery.
• Antibiotics—start broad-spectrum agents 
(oral if patient is stable; IV if patient is in 
shock); choice confirmed by bacterial culture 
and sensitivity; continued at least 14 days. 
Give at separate time from prostaglandin F2 α 
(PGF2 α) administration due to risk of 
vomiting.
• Nursing planned—amoxicillin–clavulanic 
acid 22 mg/kg PO q12h; can administer q8h 
to treat Gram-negative infections, enrofloxacin 
10 mg/kg PO, IV q24h (dogs); 5 mg/kg PO 
q24h (cats), if puppies <3 weeks of age and 
susceptibility indicates.• If ovariohysterectomy not performed and 
cervix is open—oxytocin 0.5–1 U/kg IM, SC 
(do not exceed 5 IU total); then repeat in 
1–2 hours; may require increased dose to 
attain similar degree of uterine contraction if 
>48 hours since parturition.
• PGF2 α 10–50 μg/kg SC q3–5h for 3–5 
days or 100 μg/kg SC q12h for 3–5 days; to 
evacuate uterus, ultrasound prior to cessation 
of treatment to ensure resolution of fluid 
accumulation in uterine lumen.
• Prostaglandin—may induce uterine rupture 
if the tissue is devitalized.
• Oxytocin—reduced efficacy beyond 48 
hours post partum.
  FOLLOW-UP
• Physical exam, CBC, vaginal cytologic 
• Ultrasonography—monitor evacuation of 
uterine fluid.
• Ovariohysterectomy—when medical 
• Uterine rupture and peritonitis—may occur 
with medical treatment.
• Owners may need to foster or hand-raise 
puppies and kittens.
• Ovariohysterectomy—prognosis for 
recovery good.
• Medical treatment—prognosis for recovery 
dependent on early recognition of problem by 
owner; good if early, but may adversely affect 
future reproduction.
• PGF2 α = prostaglandin F2 α.
Johnston SD, Root Kustritz MV, Olson 
PNS, eds., Canine and Feline 
Saunders, 2001, pp. 129–145.
Freshman.

Canine and Feline, Seventh Edition  907
MMovement Disorders
  BASICS
OVERVIEW
• Non-epileptic CNS disorders. 
• Characterized by the occurrence of 
continuous or episodic involuntary movements 
in a conscious, responsive animal. • Unrelated 
to epileptic activity. • Movements may involve 
the whole body or be restricted to one body 
part, e.g., one or two limbs or one side of the 
body. • Hyperkinetic movement disorders 
often occur as paroxysmal dyskinesias with long 
episodes of abnormal movements and increased 
muscle tone (dystonia) alternating with normal 
neurologic function. • Hypokinetic movement 
disorders manifest as bradykinesia or collapse. 
• Pathophysiology—abnormal CNS neural 
transmission, unrelated to epilepsy, dysfunction 
of basal nuclei, altered dopaminergic or 
serotinergic neurotransmission.
• Dogs; less common in cats. • Breed-related 
syndromes. • Age of onset variable; often <3 
years.
SIGNS
• Physical examination—unremarkable.
• Neurologic examination—unremarkable 
between episodes. • Cardiologic examination—
unremarkable between and during episodes. 
• Signs may include—repeated flexion or 
kicking, excessive lifting of one or more limbs, 
episodic muscle rigidity, muscle hypertonicity, 
difficulty initiating movements, episodic ataxia, 
kyphosis, scoliosis, backward gait, falling, 
collapse. • Description of episodes may vary 
between dog breeds. See specific references for 
detailed information on breed-specific 
syndromes. • Frequently long duration—
minutes to hours. • Differentiated from 
epileptic seizures—no autonomic signs: no 
salivation, urination, normal pupils, no postictal 
period, responsive during episode. • T riggers are 
frequent—excitement, stress, excessive exercise, 
heat. • In some dog breeds there are 
gastrointestinal signs in association with 
episodes (Border terriers, paroxysmal gluten-
sensitive dyskinesia).
• Frequently breed-specific syndromes—
Norwich terrier, chinook (paroxysmal 
dyskinesia), border collie/Australian shepherd 
dog (collapse), Scottish terrier (collapse). 
• Gluten hypersensitivity—border terrier, 
possibly also other dog breeds. • Gene 
mutations—cavalier King Charles spaniel 
(BCAN , episodic falling), Irish wolfhound 
puppies ( SLGA5 ; glycine receptor, startle 
disease), Russell terrier ( KCNJ10 , hereditary 
cerebellar ataxia associated with myokymia), 
soft-coated wheaten terrier ( PIGN ); Labrador 
retriever collapse ( DNM1 ); Chinese-crested 
dog, Kerry blue terrier (multisystem 
degeneration, SERAC1 ), Sheltie (PCK2).  DIAGNOSIS
• Epilepsy—autonomous signs: salivation, 
urination, mydriasis; typically short duration 
<1–2 minutes; postictal period. • Cardiac 
disease —bradyarrhythmias, ventricular 
tachycardia. • Metabolic, electrolyte disorders—
hypoglycemia, hypocalcemia, hypokalemia, 
hyperkalemia, hepatic encephalopathy. 
• Drugs—phenobarbital, propofol, potassium 
bromide, dopamine antagonists, metoclo-  
pramide. • Toxins—lead, copper, psychoactive 
drugs, environmental toxins. • Obsessive 
compulsive behavior—complex behavior, 
responsive, interruptible. • Episodes of spinal 
pain. • Vestibular attacks. • Rapid eye 
movement (REM) sleep disorder. • Myotonic 
myopathies—inherited, acquired. • Feline 
hyperesthesia syndrome, feline orofacial pain 
syndrome—cats, unknown etiology.
• Unremarkable. • Specific consideration—
glucose (fasted, during episode), potassium, 
sodium, ionized calcium, creatine kinase.
• Specific genetic tests—based on availability 
for the breed. • Ammonia, fasted and 
postprandial bile acids. • T4. • Serologic 
testing for gluten hypersensitivity—border 
terriers; other breeds if gastrointestinal signs. 
• Neurometabolic screening—lactate, 
pyruvate, urinary organic acids, amino acids.
IMAGING
MRI brain, spinal cord—exclude structural 
disease, frequently unremarkable.
• Video documentation of episodes. 
• Electrocardiography (ECG)—long-term, 
ambulatory (Holter); exclude arrhythmias. 
• Electroencephalography (EEG)—ambulatory 
video-EEG to exclude epilepsy. • CSF—to 
exclude CNS inflammation; frequently normal.
Frequently unremarkable.
  TREATMENT
• Avoid triggers—stress, excitement; exercise, 
heat (Jack Russell terrier). • T reat underlying 
cause if any identified. • Gluten-free diet in 
border terriers. • T rial therapy with anti -
epileptic drugs, • Dietary trials (gluten-free, 
hypoallergenic) in other dog breeds.
• Use based on low levels of evidence. 
• Diazepam 0.25–0.5 mg/kg q8h; clonazepam 0.5 mg/kg q8–12h; acetazolamide 4–8 mg/kg 
q8–12h; 4-aminopyridine 0.25–0.5 mg/kg 
q12h; fluoxetine 1–2 mg/kg q24h. • T rial 
therapy with antiepileptic drugs—gabapentin 
10–20 mg/kg q8h; levetiracetam 10–20 mg/
kg q8h; phenobarbital 2.5 mg/kg q12h.
4-aminopyridine - may cause seizures; 
acetazolamide - metabolic acidosis; fluoxetine - 
drug interactions, hyperthermia.
  FOLLOW-UP
Acetazolamide—hypokalemia, acidosis.
Avoid potential triggers. Avoid heat in Jack 
Russell terriers.
Rarely hyperthermia (death) described in 
association with collapse.
Unpredictable frequency and clinical course, 
lifelong or may spontaneously resolve.
Often appears in dogs <3 years old.
Breeding not recommended. Genetic testing 
SEE ALSO
• Exercise-Induced Weakness/Collapse in 
Labradors Retrievers. • Head T remors 
(Bobbing), Idiopathic—Dogs. • Myoclonus. 
• Shaker/T remor Syndrome, Corticosteroid 
Responsive.
• ECG = electrocardiography. • EEG = 
electroencephalography. • REM = rapid eye 
movement.
• www.omia.org • www.aht.org.uk/
cms-display/genetics_canine.html • www.
caninegeneticdiseases.net/CGD_main.htm 
• www.ofa.org/browse-by-breed
involuntary movements in dogs: paroxysmal 
dyskinesias.Vet J 2017, 220:65–71.
Author  Andrea Fischer 

908  Blackwell’s Five-Minute Veterinary Consult  
MMucopolysaccharidoses
  BASICS
OVERVIEW
• Mucopolysaccharidoses (MPS) are character -
ized by the accumulation of glycosaminogly -
cans (GAGs) in cells, and result from the 
impaired function of 1 of 11 enzymes required 
for normal GAG degradation.
• Undegraded GAGs are stored in lysosomes, 
resulting in progressive tissue and organ 
Types of MPS Reported in Dogs 
and Cats
• MPS I— α-l-iduronidase deficiency: 
dermatan and heparan sulfate stored.
• MPS II—iduronate sulfatase deficiency: 
• MPS IIIA—heparan N-sulfatase deficiency: 
heparan sulfate stored.
• MPS VI—arylsulfatase B deficiency: 
dermatan sulfate stored.
• MPS VII— β-glucuronidase deficiency: 
dermatan, heparan, and chondroitin sulfate 
stored.
• Cats—MPS I and VII (domestic shorthair 
[DSH]); MPS VI (Siamese and DSH).
• Dogs—MPS I, Plott hounds; MPS II, 
Labrador retrievers; MPS IIIA, wire-haired 
dachshunds and Huntaways; MPS VI, 
miniature pinschers, miniature schnauzers, 
miniature poodles, and Welsh corgis; MPS 
VII, mixed breeds and Belgian, White Swiss, 
and German shepherd dogs.
• Both sexes equally affected by MPS I, III, 
VI, and VII; primarily males affected by 
MPS II.
SIGNS
• Clinical signs apparent at 2–4 months of age.
• Affected animals may live several years, but 
locomotor difficulty is progressive.
• Skeletal abnormalities more severe in cats 
with MPS VI than in those with MPS I; some 
MPS VI cats develop posterior paresis from 
• Dwarfism (except cats with MPS I).
• Severe bone disease (dysostosis multiplex), 
degenerative joint disease, facial dysmorphia.
• Hepatomegaly (except cats with MPS VI).
• Corneal clouding–~8 weeks of age.
• Enlarged tongue (dogs).
• Heart valve thickening, resulting in left- or 
right-sided heart failure.
• Excess urinary excretion of GAG.
• Manipulation of the head or neck usually 
painful.
• MPS transmission is autosomal recessive, 
except MPS II, which is X-linked recessive.
• In-breeding increases risk.  DIAGNOSIS
• Metachromatic granules within neutrophils 
and lymphocytes–suggest MPS; also observed 
with GM2 gangliosidosis, which, unlike MPS, 
is characterized by progressive neurologic 
disease and early death.
• Corneal clouding—also observed in other 
storage diseases, including acid lipase deficiency, 
GM1 and GM2 gangliosidosis, and mannosidosis; 
lysosomal enzyme panels can be performed to 
definitively diagnose the type of disorder.
• Radiographic appearance of MPS is 
characteristic; other disorders with similarities 
include congenital hypothyroidism, 
epiphyseal dysplasia, and hypervitaminosis A.
• Wright’s-stained blood films reveal 
neutrophils and monocytes containing 
numerous distinctive metachromatic granules 
(Alder–Reilly bodies).
• Granules indistinct in animals with MPS I.
• Granules usually inapparent when stained 
with Diff-Quik.
• Occasional lymphocytes have vacuoles with 
metachromatic granules, particularly in MPS 
VII.
• Wright’s stained cytologic preparations of 
lymph node, liver, bone marrow, and joint 
fluid specimens reveal Alder–Reilly bodies 
within cells.
• Presence of excess GAG in urine usually 
indicates MPS.
• Definitive diagnosis made by measuring 
lysosomal enzyme activity in serum, leukocyte 
pellets, or frozen liver.
IMAGING
• Radiography—low bone density with thin 
cortices.
• Epiphyseal abnormalities.
• In some cats, proliferative bone is present 
around all articular facets of vertebrae, 
causing fusion of cervical vertebrae.
Specialized laboratories can measure lysosomal 
enzyme activity in leukocyte pellets and detect 
specific gene mutations for some disorders.
Distended lysosomes seen in cells of many tissues 
examined by light and electron microscopy.
  TREATMENT
• Bone marrow transplant (BMT)—after 
successful engraftment, donor-derived normal leukocytes provide missing enzyme to various 
tissues; when performed at a very early age, 
affected animals lead near-normal lives; not as 
helpful when performed after skeletal maturity; 
unaffected sibling is needed as a donor.
• Gene therapy has been effective in some 
animal models.
Affected animals are susceptible to viral and 
bacterial respiratory infection. Antibiotics 
  FOLLOW-UP
• Avoid in-breeding.
• Enzyme assays should be performed to 
diagnose heterozygotes.
• Prognosis reasonably good in animals 
treated with BMT.
• Untreated animals usually develop severe 
skeletal and joint disease and may become 
nonambulatory at 3–5 years of age or earlier.
• BMT = bone marrow transplant.
• DSH = domestic shorthair cat.
• GAG = glycosaminoglycan.
• MPS = mucopolysaccharidoses.
Haskins M, Casal M, Ellinwood NM, et al. 
Animal models for mucopolysaccharidoses 
and their clinical relevance. Acta Paediatr 
Suppl 2002, 91:88–97.
Author  Mary Anna Thrall

Canine and Feline, Seventh Edition  909
MMultidrug-Resistant Infections
  BASICS
Antimicrobial resistance (AMR) is the ability 
of microbes to grow in the presence of 
antimicrobial agents that would normally kill 
them or inhibit their growth. Multidrug-
resistant (MDR) infections are those that are 
resistant to more than one class of 
AMR can develop in several ways:
• Use of antimicrobials creates selection 
pressure, allowing growth of bacteria resistant 
to a specific drug by decreasing competition 
with susceptible organisms.
• Antimicrobial-resistant bacteria can share 
genetic elements, conferring resistance to 
other bacteria.
• Spontaneous new mutations can develop 
that allow bacterial survival in the face of 
• MDR infections occur through any of these 
mechanisms; resistance is often additive with 
antimicrobial use over time.
Any tissue affected by bacterial infections may 
be affected by antimicrobial-resistant bacterial 
infections. Some examples are:
• Renal/urologic—recurrent urinary tract 
• Skin—abscesses, pyoderma.
• Respiratory—pneumonia.
• Musculoskeletal—surgical site infections.
• Gastrointestinal—gastrointestinal pathogens 
such as Campylobacter  spp., Salmonella  spp., 
Escherichia coli , Enterococcus  spp.
• Hepatobiliary—ascending cholangitis/
cholecystitis.
• Cardiovascular—endocarditis.
GENETICS
N/A
Due to a lack of robust surveillance, 
prevalence of MDR infections in dogs and 
cats is unknown; however, studies suggest 
between <1 and 50% of bacteria cultured 
from companion animals are MDR, 
depending on geographic region.
N/A
Species
N/A
N/APredominant Sex
N/A
SIGNS
Bacterial infections that do not resolve with 
first-line empiric antimicrobial therapy 
should cause suspicion for AMR.
• No or minimal response to antimicrobial 
therapy.
• History of previous course(s) of anti -
microbial therapy.
• Exposure to humans or animals with MDR 
• Recent hospitalization and/or surgery.
• Raw food diet.
Depends on site of infection.
CAUSES
Any bacteria can become resistant to 
antimicrobials. Common AMR bacterial 
pathogens include:
• Methicillin-resistant Staphylococcus 
pseudintermedius  (MRSP).
• Methicillin-resistant Staphylococcus aureus  
(MRSA).
• MDR Enterococcus faecalis  and Enterococcus 
faecium .
• Extended-spectrum beta-lactamase (ESBL) 
producing Gram-negative bacteria including:
◦ E. coli .
◦ Salmonella enterica .
◦ Klebsiella pneumoniae .
◦ Pseudomonas aeruginosa .
◦ Proteus mirabilis .
◦ Enterobacter  spp.
• Antimicrobial use.
• Hospitalization.
• Surgery.
• Co-habitation with health care worker.
• Co-habitation with human colonized with 
MRSA.
• Co-habitation with animal or human 
infected or colonized with AMR organism.
  DIAGNOSIS
Bacterial infections, nonbacterial infections 
and other inflammatory diseases can mimic 
AMR bacterial infections, in that clinical 
response is not achieved with empiric 
• T reating a microbe inherently resistant to 
empiric drug chosen (e.g., treating anaerobic 
infection with a drug ineffective against 
anaerobes) or using drug that does not 
penetrate site of infection.• Viral, fungal, or protozoal infections.
Findings are dependent on location of 
• CBC may lack abnormalities or range from 
leukocytosis and neutrophilia to neutropenia 
with degenerative left shift.
• Chemistry abnormalities associated with 
site of infection (e.g., azotemia with 
pyelonephritis).
• Urinalysis may reveal bacteriuria and pyuria 
in patients with urinary tract infections.
• Quantitative bacterial culture and 
susceptibility testing are required for 
identification of AMR and MDR infections.
• Cytologic examination using a 
Romanowsky-type stain (e.g., Diff-Quik) 
and/or Gram stain of samples obtained for 
culture may help with culture interpretation, 
especially if more than one organism is 
cultured or suspected.
IMAGING
Imaging studies should identify source of 
infection and guide sampling for bacterial 
culture and susceptibility testing.
Sampling of site of infection is required for 
diagnosis and for guiding therapy; such 
procedures may include swabs of skin wounds 
or lesions, cystocentesis, thoracocentesis, 
abdominocentesis, pyelocentesis, airway 
samples (transtracheal, endotracheal wash or 
bronchoalveolar lavage).
Findings are dependent on site of infection. 
In general, active infections would be 
expected to contain innate immune cells and 
intracellular bacteria.
  TREATMENT
• If hospitalization is required, patient should 
be isolated and proper personal protective 
equipment (gloves, gowns, eye or face shield, 
as indicated) utilized to prevent nosocomial 
infections of other patients and colonization 
of caregivers.
• Therapy dependent on location and type of 
• T reatment of underlying disease and 
addressing predisposing risk factor(s) is 
critical to clear infection and prevent 
recurrence (e.g., removal of urinary cystoliths 
to resolve bladder infection).
• Surgical debridement of wound infections 
may be necessary.

910  Blackwell’s Five-Minute Veterinary Consult  
M• Topical antiseptic therapy for localized 
cutaneous infections, such as MRSP and 
MRSA, is recommended in lieu of systemic 
antimicrobials, when possible.
• For cutaneous wounds, bandaging is 
recommended to protect wound and prevent 
spread of AMR organisms.
• For patients with urinary or gastrointestinal 
infections, patients should eliminate in areas 
amenable to disinfection.
ACTIVITY
Social activities such as daycare, boarding, 
grooming, dog parks, should be avoided until 
infection is resolved.
DIET
Raw food diets are discouraged due to risk of 
bacterial pathogen contamination.
• Educate clients on potential side effects of 
• Ethical dilemmas regarding using drugs 
critically important to human medicine 
should be discussed.
• Educate clients on handwashing and 
cleaning environment to protect themselves 
and household from MDR pathogens.
N/A
• Antimicrobial therapy should be based 
upon bacterial culture and susceptibility 
(C&S) testing.
• Use of highest priority drugs of critical 
importance for human health is controversial 
in veterinary medicine. If antimicrobial 
selection choices are limited to drugs of highest 
priority (e.g., 3rd and 4th generation 
cephalosporins, carbapenems) at a minimum, 
the following criteria should be applied: (1) 
Use is supported by C&S testing. (2) There is 
no other reasonable alternative or alternatives 
are contraindicated for the patient (e.g., 
aminoglycosides for animal with renal disease). 
(3) Infection is not improving with current 
management (e.g., topical therapy, wound 
debridement, bandaging). (4) There is good 
chance that treatment will be curative; these 
drugs should not be used in pets likely to have 
recurrent infections. (5) A specialist in 
infectious disease, microbiology, and infectious 
disease pharmacology should be consulted.
Immunosuppressive drugs.PRECAUTIONS
Ensure that bacterial C&S-based 
antimicrobial decisions are appropriate for 
site of infection (e.g., choose lipophilic drugs 
with good tissue penetration if treating 
parenchymal disease such as pyelonephritis). 
Inadequate drug concentration at site of 
infection may lead to further AMR.
N/A
For localized and/or mild superficial 
pyoderma, topical antiseptics are encouraged 
in lieu of antimicrobials. These may include 
chlorhexidine or benzoyl peroxide shampoos, 
lotions and sprays; acetic, lactic and malic 
acids, benzoyl peroxide and silver sulfadiazine 
gels, creams and wipes. Mupirocin ointment 
may be appropriate topical antimicrobial for 
MRSA infections if supported by bacterial 
C&S.
  FOLLOW-UP
• Confirmation of effective antimicrobial 
treatment via repeated bacterial culture and 
cytology should be performed during therapy 
and after cessation of therapy to ensure 
• Consider reevaluation of patient 72 hours 
after initiation of therapy to evaluate for 
expected response.
• Prevention of AMR infections involves 
judicious use of antimicrobials. In patients 
likely to have recurrent infections (e.g., 
aspiration pneumonia in patients with 
megaesophagus) using the minimal effective 
duration of therapy is recommended.
• As nosocomial infections are likely to 
exhibit AMR, appropriate infection control 
protocols should be used in veterinary 
hospital settings.
In some cases, side effects of antimicrobial 
therapy required to treat AMR and MDR 
infections may result in morbidity, precluding 
clearance of infection.
AMR and MDR infections are not necessarily 
more virulent than antimicrobial-susceptible 
infections. With appropriate antimicrobial 
selection, dose, and duration of therapy, 
patients without unresolved predisposing 
factors are expected to have similar prognosis 
as those with antimicrobial-susceptible 
infections.  MISCELLANEOUS
• Risk factors that break down immune 
barrier of urinary bladder (e.g., ectopic 
ureters, urinary calculi, urachal diverticulum, 
transitional cell carcinoma) are associated 
with AMR and MDR urinary tract infections.
• Atopy (chronic or recurrent pyoderma).
• Megaesophagus and chronic bronchitis 
(chronic or recurrent upper and lower 
respiratory infections).
• Implants (e.g., bone plates) may be 
associated with surgical site infections.
N/A
There have been sporadic reports of both 
zoonotic and reverse-zoonotic transmission of 
AMR and MDR pathogens between animals 
Female dams or bitches can pass AMR 
bacteria to their offspring, thus causing 
colonization or infection with AMR 
organisms despite a lack of previous 
antimicrobial exposure.
SYNONYMS
• Antibiotic-resistant infection.
• Antimicrobial-resistant infection.
SEE ALSO
Methicillin-Resistant Staphylococcus .
• AMR = antimicrobial resistance.
• C&S = culture and susceptibility.
• ESBL = extended-spectrum beta-lactamase.
• MDR = multidrug-resistant.
• MRSA = methicillin-resistant Staphylococcus 
aureus .
• MSRP = methicillin-resistant Staphylococcus 
pseudintermedius .
• International Society for Companion 
Animal Infectious Diseases: www.iscaid.org
• Antimicrobial Resistance and Stewardship 
Initiative: https://arsi.umn.edu/
Weese JS, Giguere S, Guardabassi L, et al. 
ACVIM consensus statement on therapeutic 
antimicrobial use in animals and 
Author  Jennifer L. Granick
Consulting Editor  Amie KoenigMultidrug-Resistant Infections  (continued)

Canine and Feline, Seventh Edition  911
MMultiple Myeloma
  BASICS
OVERVIEW
• Defined as malignant plasma cells in the 
bone marrow. •  Diagnosis requires documen­
tation of bone marrow plasmacytosis, 
osteolytic bone lesions, and serum or urine 
myeloma proteins (M ­component).
• Proliferation of malignant plasma cells that 
produce immunoglobulins or subunits. 
• Immunoglobulins may polymerize and 
increase serum viscosity. •  Bleeding disorders 
due to paraprotein coating of platelets, 
thrombocytopenia, hyperviscosity, or 
interference with coagulation factors. 
• Nephrotoxicity due to protein deposition 
of amyloid or direct effect of the protein on 
renal tubular epithelial cells. •  Hypercalcemia 
due to osteoclast activation and bone lysis.
• Musculoskeletal—multiple punctate areas of 
bone lysis in the absence of bony proliferation. 
• Nervous, cardiovascular, and respiratory—
abnormalities secondary to hyperviscosity. 
• Soft tissues—neoplastic infiltration.
Incidence/Prevalence
• Dogs—1% of all malignancies; <8% of 
hematopoietic malignancies; 3.6% of all bone 
tumors. •  Cats—<1% of hematopoietic tumors.
Dogs and cats; 6–13 years.
SIGNS
Due to bone infiltration and lysis, immuno ­
globulins produced, and infiltration of organ(s).
Dogs
• Lethargy, weakness (62%). •  Lameness 
(47%). •  Bleeding diathesis (37%): gingiva 
and epistaxis. •  Funduscopic abnormalities 
including retinal hemorrhage or detachment 
and tortuous vessels (35%).
Cats
Anorexia, weight loss, malaise, polydipsia, 
polyuria.
  DIAGNOSIS
• Ehrlichiosis, leishmaniosis. •  Metastatic 
bone lesions. •  Rheumatoid arthritis.
Dogs
• Hemogram—nonregenerative anemia 
(66%); neutropenia (25%); thrombocytopenia 
(33%). •  Chemistry—hyperglobulinemia, 
hypercalcemia (10–25%), azotemia (33%). 
• Urinalysis: proteinuria, isosthenuria, 
cylindruria, pyuria, hematuria, or bacteriuria.OTHER LABORATORY TESTS
• Serum protein electrophoresis—
monoclonal gammopathy in the beta or 
gamma region, and occasionally a biclonal 
gammopathy will be present. •  Urine protein 
electrophoresis—Bence ­Jones proteins in 
25–40%. •  Coagulation profile— ∼50% will 
have abnormal coagulation values.
IMAGING
• Radiography (dogs)—25–66% have multi ­ 
focal, lytic lesions or diffuse osteoporosis. 
• Radiography (cats)—bony lesions rare, more 
common for visceral organ infiltration (myeloma ­
related disorder). •  Ultrasonography—detect 
changes in visceral organs.
• Diagnosis depends on identifying at least 3 
of 4 pathologies: ◦ Monoclonal gammopathy. 
◦ Lytic bone lesions. ◦ Bence Jones proteinuria. 
◦ Bone marrow cytology: >20% plasma cells 
or >5% malignant plasma cells. •  For cats—
bone marrow involvement is rare, and hence 
diagnosis is based upon the identification of 
malignant plasma cells within the visceral 
organs (myeloma ­related disorder).
  TREATMENT
• Hospitalization if azotemia, hypercalcemia, 
bleeding disorder, or bacterial infection. 
• Plasmapheresis lowers protein burden—for 
symptomatic patient, withdraw a volume of 
venous blood, centrifuge, discard plasma, and 
return red blood cells to patient in IV crystalloid 
fluids. •  Phlebotomy for hyperviscosity; replace 
with an equal volume of isotonic fluids IV. 
latest information regarding treatment.
• Inform client that chemotherapy is palliative 
but long remissions are possible. •  Warn 
client that relapse will occur. •  Discuss side 
effects, which depend on the drugs used.
Areas nonresponsive to chemotherapy or 
solitary lesions can be removed surgically.
Radiation therapy can be palliative and highly 
effective for managing osteolytic bone cancer 
pain. Indications include painful bone lesions, 
spinal cord compression, pathologic fractures 
(after fracture stabilization), or a large soft tissue 
mass. Consult with a radiation oncologist.
• Dogs—melphalan and prednisone; 
cyclophosphamide can be used in addition to or in place of melphalan. •  Cats—melphalan 
and prednisone. •  IV aminobisphosphonate 
drugs for management of hypercalcemia and 
palliation of bone pain. •  Consult a veterinary 
oncologist or reliable drug resource for dosages.
• Melphalan—delayed thrombocytopenia. 
• Cyclophosphamide—sterile hemorrhagic 
cystitis.
  FOLLOW-UP
• CBC and chemistry every 2 weeks for 2 
months, then monthly. •  Serum electro­
phoresis and/or Bence Jones proteinuria 
monthly until at least 50% decrease in 
baseline values, then once every 2–3 months.
Chemotherapy may cause leukopenia or 
thrombocytopenia, anorexia, alopecia, 
hemorrhagic cystitis, and/or pancreatitis.
• Improvement in clinical signs and 
laboratory abnormalities expected within 
3–6 weeks. •  Radiographic abnormalities 
could take longer and be partial.
Dogs
• Median survival with alkylating agent and 
prednisone—18–30 months. •  Overall 
response rate >90%. •  Hypercalcemia, 
extensive bone lysis, or Bence ­Jones 
proteinuria may have shorter survival. 
• Death typically due to kidney failure, 
secondary infections, or bone/spinal pain.
Cats
Survival with alkylating agents and 
prednisone—2–9 months.
SEE ALSO
Vail D. Myeloma ­related disorders. In: 
Small Animal Clinical Oncology, 5th ed. 
St. Louis, MO: Elsevier Saunders, 2013, 
pp. 665–678.

912  Blackwell’s Five-Minute Veterinary Consult  
MMurmurs, Heart
  BASICS
Vibrations caused by disturbed blood flow.
Timing of Murmurs
• Systolic murmurs occur between S1 and S2 
(systole).
• Diastolic murmurs occur between S2 and 
S1 (diastole).
• Continuous and to-and-fro murmurs occur 
throughout all or most of the cardiac cycle 
(systole and diastole).
• Continuous murmurs are usually 
accentuated near S2 and to-and-fro murmurs 
are usually absent near S2.
Grading Scale for Murmurs
• Grade I—barely audible.
• Grade II—soft, but easily auscultated. Does 
not radiate far from point of maximal 
intensity.
• Grade III—intermediate loudness; heard 
easily some distance from point of maximal 
intensity (PMI), but not to opposite side of 
chest; most hemodynamically important 
murmurs are at least grade III.
• Grade IV—loud murmur radiating widely, 
often including opposite side of chest.
• Grade V—very loud, audible with 
stethoscope barely touching the chest; 
palpable thrill.
• Grade VI—very loud, audible without the 
stethoscope touching the chest; palpable 
thrill.
Configuration
• Plateau murmurs have uniform loudness 
and are typical of atrioventricular (AV) valve 
regurgitant murmurs such as mitral and 
tricuspid insufficiency and also ventricular 
• Crescendo–decrescendo murmurs get 
louder and then softer and are typical 
of ejection murmurs such as pulmonic 
and aortic stenosis and also atrial septal 
defect.
• Decrescendo murmurs start loud and then 
get softer and are typical of diastolic murmurs 
such as aortic or pulmonic insufficiency and 
mitral or tricuspid stenosis.
Location
Dogs
• Mitral area—left fifth intercostal space at 
costochondral junction.
• Aortic area—left fourth intercostal space 
above costochondral junction.
• Pulmonic area—left second to fourth 
intercostal space at sternal border.
• T ricuspid area—right third to fifth inter  - 
costal space near costochondral junction.Cats
• Mitral area—left fifth to sixth intercostal 
adjacent to the sterum.
• Aortic area—left second to third intercostal 
space just above the pulmonic area.
• Pulmonic area—left second to third intercostal 
space adjacent to the sterum.
• T ricuspid area—right fourth to fifth 
intercostal space adjacent to the sterum.
• Disturbed blood flow associated with high 
flow through normal or abnormal valves or 
with structures vibrating in the blood flow.
• Flow disturbances associated with outflow 
obstruction or forward flow through stenosed 
valves or into a dilated great vessel. Intensity 
of the murmur generally correlates with the 
severity of the stenosis.
• Flow disturbances associated with 
regurgitant flow through an incompetent 
valve, septal defect, or patent ductus 
arteriosus.
SIGNS
Relate to cause of the murmur.
CAUSES
Systolic Murmurs
• Myxomatous valve disease (mitral and 
tricuspid valves).
• Cardiomyopathy and AV valve 
• Physiologic flow murmurs.
• Anemia.
• Mitral and tricuspid valve dysplasia.
• Systolic anterior mitral motion.
• Dynamic right ventricular outflow 
• Dynamic subaortic stenosis.
• Atrial septal defect.
• Ventricular septal defect (VSD).
• Pulmonic stenosis.
• Tetralogy of Fallot.
• Mitral and tricuspid valve endocarditis.
Continuous and To-and-Fro Murmurs
• Patent ductus arteriosus (continuous).
• VSD with aortic regurgitation (to-and-fro).
• Aortic stenosis with aortic regurgitation 
(to-and-fro).
Diastolic Murmurs
• Mitral and tricuspid valve stenosis.
• Aortic and pulmonic valve endocarditis.
Cardiac disease.  DIAGNOSIS
Differential Signs
• Must differentiate from other abnormal 
heart sounds—split sounds, ejection sounds, 
gallop sounds, and clicks.
• Must differentiate from abnormal lung 
sounds and pleural rubs; listen to see if timing 
of abnormal sound is correlated with 
respiration or heartbeat.
Differential Causes
• Pale mucous membranes support diagnosis 
of anemic murmur.
• Location and radiation of murmur and 
timing during cardiac cycle can help 
determine cause (see Figure 1).
• Anemia in animals with anemic murmurs.
• Polycythemia in animals with right-to-left 
shunting congenital defects.
• Leukocytosis with left-shift in animals with 
N/A
IMAGING
• Thoracic radiography—useful for evaluating 
heart size and pulmonary vasculature to help 
determine cause and significance of murmur.
• Echocardiography—allows definitive 
diagnosis of cause of murmur.
• Doppler studies sometimes required to 
confirm cause of murmur.
• Electrocardiography may be useful in 
assessing heart enlargement patterns in 
animals with murmurs.
• Blood cultures and serology for Bartonella  if 
suspect endocarditis.
  TREATMENT
• Outpatient unless heart failure is evident.
• Base decisions on the cause of the murmur 
and associated clinical signs.
• None indicated for murmur alone.
N/A
N/A

Canine and Feline, Seventh Edition  913
M
N/A
N/A
  FOLLOW-UP
Low-grade systolic ejection murmurs in 
puppies may be physiologic; most resolve by 
6 months of age. If murmur still present after 
6 months, include diagnostic imaging.
If murmur is associated with structural heart 
disease, may see signs of congestive heart 
failure (e.g., coughing, dyspnea, and ascites) 
or exercise intolerance.
• Murmurs present since birth generally 
associated with a congenital defect or 
physiologic flow murmur.
• Acquired murmurs in geriatric, small-breed 
dogs usually associated with degenerative 
valve disease.
• Acquired murmurs in large-breed dogs usually 
associated with dilated cardiomyopathy.
• Acquired murmurs in geriatric cats can be 
associated with cardiomyopathy, 
hyperthyroidism or innocent.
None
Murmurs in puppies and kittens may reflect a 
congenital defect and thereby influence 
decisions on breeding that animal or 
repeating the mating.
• PMI = point of maximal intensity.
• S1 = first heart sound.
• S2 = second heart sound.
• VSD = ventricular septal defect. Suggested Reading
Caivano D, Dickson D, Martin M, Rishniw 
M. Murmur intensity in adult dogs with 
pulmonic and subaortic stenosis reflects 
disease severity. J Small Anim Pract 2018, 
59(3):161–166.
Gompf RE. The history and physical 
examination. In: Smith FWK, Tilley LP , 
Oyama MA, Sleeper MM, eds, Manual of 
Canine and Feline Cardiology, 5th ed. St. 
Louis, MO: Saunders Elsevier, 2016.
Keene B, Smith FWK, Tilley LP , Hansen B. 
Rapid Interpretation of Heart Sounds, 
Murmurs, Arrhythmias, and Lung Sounds: 
A Guide to Cardiac Auscultation in Dogs 
and Cats, 3rd ed. CD-ROM and Manual. 
Philadelphia, PA: Elsevier, 2015.
Consulting Editor  Michael AherneInnocent or physiologic
(low grade–no other cardiac signs)
Anemia
Fever
Anxiety
Puppies and kittens <6 months oldSystolic
Left hemithorax
2 to 4 ICS
(heart base)
Pulmonic stenosis
 Aortic stenosis
Tetralogy of Fallot
Atrial septal defectMitral valve dysplasia
Mitral valve endocardiosis
Mitral valve bacterial
endocarditisAortic stenosisVSD Tricuspid valve dysplasia
Tricuspid valve endocardiosis
Tricuspid valve bacterial endocarditis5 to 6 ICS
(heart apex)3 to 5 ICS 2 to 4 ICSBacterial endocarditis (aortic or pulmonic valve) Right hemithorax
Aortic regurgitation secondary to high VSD
Mitral or tricuspid valve stenosis (rare)Aortic stenosis with aortic insu fficiency
VSD with aortic insuf ficiencyPatient ductus arteriosus
Arteriovenous fistula
Sinus of Valsalva aneurysm or
coronary artery rupture into the right heart
Aortic pulmonary window
with left-to-right shuntTo and fro Diastolic ContinuousMurmur
Organic
Figure 1 .
Algorithm for differential diagnosis of murmurs.(continued)  Murmurs, Heart

914  Blackwell’s Five-Minute Veterinary Consult  
MMuscle Rupture (Muscle Tear)
  BASICS
OVERVIEW
A normal muscle may be stretched, pinched, 
or injured directly, resulting in fiber disrup-
tion, weakening, and immediate or delayed 
separation of the uninjured portions. 
Alternatively, the muscle structure may be 
compromised by systemic or iatrogenic 
conditions, and normal activity may cause 
muscle disruption. The rupture may be 
complete or incomplete, and it may be 
mid-substance or at the muscle–tendon 
junction. The acute stage is characterized by a 
typical inflammatory reaction that becomes 
chronic with collagen maturation, cross-
linking, fibrosis, and adhesion development 
over time. Frequently the acute phase is 
overlooked, as the signs may be temporary 
and respond well to rest. The chronic effects 
are often progressive and unresponsive to 
support therapies.
• Limb and masticatory muscles are the 
primary structures affected.
• T raumatic injury is indiscriminate, 
although certain activities may predispose 
because of exposure.
• The ruptures that are apparently unrelated 
to trauma seem to affect middle-aged to 
older working dogs, with no reported sex 
• Cats are affected less frequently than  
dogs.
SIGNS
Acute Injury
• Immediate lameness that is characterized by 
the specific muscle affected.
• Localized swelling, heat, and pain.
• Generally present for a few days to a  
week.
• Animals may experience re-injury.
Chronic Phase (If It Develops)
• Progressive.
• Painless.
• Usually associated with scar tissue that 
impedes normal function of an extremity.
• T rauma.
• Repeated overuse.
• Overextension.
• Myositis.
• Degenerative (unknown etiology).
• Myopathy secondary to medical conditions 
such as Cushing disease.
• Apparent risk factor for dogs is involvement 
in hunting, tracking, or similar activities in 
the outdoors.Gait Analysis and Physical Examination 
Findings
Various disorders will result in characteristic 
gait abnormalities and pain elicited on 
specific limb manipulation—a few of which 
are listed here.
• Psoas muscle injury:
◦ Pain on internal rotation with extension 
or abduction of the pelvic limb.
◦ Pain on palpation of the lesser trochanter 
of the affected femur.
◦ Short, choppy gait.
• Gracilis, semimembranosus, and semitendi-
nosus muscle contractures:
◦ In late stages, these animals are typically not 
painful on palpation of the gracilis, semitendi -
nosus or semimembranosus muscles.
◦ Palpation of a fibrous band in the area of 
the affected muscle is also apparent.
◦ Shortened stride with medial rotation of 
the paw, internal rotation of the hock, and 
external rotation of the calcaneus, with 
internal rotation of the stifle in late phase of 
the forward stride.
• Infraspinatus muscle contracture:
◦ Significant forelimb lameness with 
circumduction of the affected limb.
◦ Marked elbow adduction/foot abduction; 
upon flexion of the elbow, the distal 
antebrachium will deviate laterally.
◦ Fibrous band will be apparent on 
palpation of the infraspinatus muscle.
• Quadriceps contracture:
◦ Typically occurs with limb disuse/
immobilization after femur fracture 
fixation in young dogs without appropriate 
◦ Patient will be unable to flex stifle.
• Achilles mechanism injuries:
◦ Non-weight-bearing lameness with soft 
tissue swelling proximal to the calcaneous for 
tendinous avulsions (mid-substance tears will 
present with mid gastroc pain and swelling).
◦ Hyperflexion of the tarsus.
◦ Hyperflexion of the digits, if superficial 
digital flexor is unaffected (crab claw).
• Sartorius muscle injury/fibrosis:
◦ Scant reports in the veterinary literature.
◦ Nonpainful, non-weight-bearing pelvic 
limb.
◦ Palpable fibrous band in the area of the 
sartorius muscle.
◦ Short, choppy gait, characterized by an 
inability to extend the hip.
  DIAGNOSIS
• Neurologic dysfunction—recognized by 
neurologic abnormalities.• Tendon rupture—visible or palpable 
disruption in the tendon.
• Origin/insertion avulsion fracture—radio-
graphic evidence of bone fragment defect and 
• Luxation/subluxation—palpable or 
radiographic evidence of joint instability or 
malalignment.
No injury-specific findings.
• Creatine phosphokinase (CPK) may be 
elevated in acute cases.
• No known specific tests available.
IMAGING
• Soft tissue swelling may be evident in the 
early stages.
• Calcification of muscle can occur in the 
traumatized area in chronic situations.
• Avulsion fractures and calcification of the 
tendon of insertion or origin may be noted 
on radiographs.
• Local swelling and disorganization of the 
normal muscle fiber orientation may be seen 
at the site of injury in acute cases.
• Scar tissue and contracted areas of fibrous 
tissue can be seen in the muscle in chronic 
cases—noted as hyperechoic foci in the 
muscle belly of concern.
• Measurable differences between normal and 
abnormal sides may be useful in documenting 
the affected muscle site.
Cross-Sectional Imaging Studies
• CT findings—produces better tissue 
contrast than the above but still constrained 
to an axial plane of view.
• MRI findings—edema and hemorrhage 
cause a change in the signal that can be 
differentiated from changes due to fibrous 
tissue replacement of muscle. This allows 
localization of the problem and helps to 
identify the type of problem.
The presence of fibrous tissue and the loss 
of muscle cells may be documented. 
Differentiating disuse atrophy from neuro-
logic atrophy and from injury-induced 
fibrosis may be impossible without corrobo-
rating evidence.
  TREATMENT
• There is no documented evidence to 
support a single “best” way to treat acute 
muscle injuries, preventing fibrous

Canine and Feline, Seventh Edition  915
M contracture and adhesions. It is generally 
believed that immediate post-injury care 
should involve rest, local cold application 
followed within hours (24–48 hours) by heat, 
and passive physical therapy (movement). 
Severe, strict immobilization (via cast or cage) 
is potentially contraindicated as it may 
encourage muscle contracture and muscle 
fibrosis, leading to irreversible long-term 
debilitation. Light or non-weight-bearing 
activity is appropriate for an extended period 
of time (4–6 weeks). Analgesics and 
anti-inflammatory drugs should be recom-
mended for several days to weeks. Surgery 
may be performed within a few days of the 
injury to repair obvious, acute muscle rupture 
that results in a separation of the uninjured 
muscle segments. An essential part of muscle 
repair is effective tension relief for the injured 
muscle so that healing can occur without 
disruption as function returns. Internal or 
external orthopedic devices may be necessary 
to provide effective tension relief (transarticu-
lar orthopedic implants or orthotics). Owners 
should be made aware of the possibility of 
scar-related problems affecting the patient’s 
gait in the long term.
• Once the muscle injury becomes chronic 
and associated with contracture or adhesions, 
treatment is aimed at function salvage. 
Surgical release of the adhesions or fibrous 
tissue bands is often accompanied by 
instantaneous symptomatic relief. The 
prevention of readhesion and progressive 
contracture is much less rewarding.
• Specific muscle injuries have widely 
disparate prognoses. Infraspinatus and psoas 
muscle contractures respond well to surgical excision of the tendon of insertion. Gracilis, 
semimembranosus, and semitendinosus 
contractures have a 100% recurrence rate after 
surgical resection. Quadriceps contracture has 
a similarly dismal failure rate after surgery.
• Muscle injuries that have healed in an 
elongated state have a better prognosis for 
surgical improvement of function than 
contracted muscles. The most common 
elongation injury affects the muscles of the 
calcaneus (Achilles) group. Hock hyperflexion 
can be surgically reconstructed to return these 
animals to relatively normal function. This is 
usually accomplished by shortening the 
Achilles tendon rather than the injured 
muscle or musculotendinous junction.
None are specific. Anti-inflammatory drugs 
may be indicated in acute situations.
Immobilization of the injured muscle in a 
position that allows adhesions to develop to 
nearby bone will often result in “tie down” 
contractures.
  FOLLOW-UP
Repetitive range-of-motion monitoring and 
recheck examination.PREVENTION/AVOIDANCE
Early inflammation control and non-weight-
bearing passive physical therapy accompanied 
by strict cage rest may be beneficial.
Contracture of the muscle and fibrous 
replacement of muscle tissue.
Specific to the muscle and the type of injury.
Joint hypermobility, angular limb deformities, 
flexion/extension joint abnormalities.
Growth plate fractures in young dogs, 
particularly distal femoral Salter–Harris 
fractures, are associated with quadriceps 
contracture.
• CPK = creatine phosphokinase.
Vaughan LC. Muscle and tendon injuries in 
dogs. J Small Anim Pract 1979, 
20:711–736.
Consulting Editor  Mathieu M. Glassman(continued)  Muscle Rupture (Muscle Tear)

M
916  Blackwell’s Five-Minute Veterinary Consult  
MMushroom Toxicoses
  BASICS
Cytotoxic Mushroom Poisoning
• Amanita verna  (European springtime 
destroying angel), A. virosa  (destroying 
angel), A. phalloides  (death cap, green death 
cap), A. bisporigera  (destroying angel), 
A. ocreata , A. farinosa  and likely many others 
in the Amanita  genus. Other important 
species include Galerina autumnalis ,  
G. marginata  (white rot fungus), G. venenata  
(deadly lawn galerina), G. sulciceps , G. 
venenata , Lepiota helveola , L. brunneoincanata , 
L. castanea , L. citrophylla , and L. subincarnata . 
• A number of Conocybe  species (notably  
C. filaris ), which are very commonly found in 
urban lawns and other urban environments, 
have been implicated in many cases of 
fulminant hepatic failure in dogs.
Primary Acute Nephrotoxic Mushroom 
Poisoning
Amanita proxima , A. pseudoporphyria , 
A. smithiana .
Delayed Nephrotoxic Mushroom 
Poisoning
Cortinarius gentilis  (deadly cort), C. orellanus  
(fool’s webcap), C. speciosissimus , C. splendens .
Hallucinogenic  Mushroom Poisoning
• Psilocybe  genus (most species). • Panaeolus 
foenisecii  (haymaker mushroom), P . fimicola , 
P . subbalteatus . • Conocybe smithii  (bog 
conocybe). • Gymnopilus junonius  (big 
laughing gym). • Copelandia  genus. • Pluteus  
genus. • Possibly Stropharia  genus. • Liquid 
extracts are commonly sold.
Autonomic Toxicity Mushroom 
Poisoning
• Clitocybe  genus (most species). • Inocybe  
genus (most species).
Psychoactive  Isoxazole Mushroom 
Poisoning
Amanita cokeri  (Coker’s amanita), A. 
cothurnata , A. gemmate , A. muscaria  (fly 
agaric, fly mushroom, fly amanita, Satan’s 
mushroom, sacred mushroom), A. pantherina .
Rapid -Onset Myotoxic Mushroom 
Poisoning
Russula subnigricans .
Delayed-Onset Myotoxic Mushroom 
Poisoning
Tricholoma equestre .
Gamma-Aminobutyric Acid (GABA)  
Antagonist Mushroom Poisoning
Gyrometra  genus (many species; false morels).
Gastrointestinal (GI) Irritant Mushroom 
Poisoning
A wide variety of mushrooms can induce GI 
irritation when ingested.• Paxillus syndrome: Paxillus involutus  
(brown roll-rim, poisonous paxillus, brown 
chantarelle, roll-rim fungus).
• Major toxins are amatoxins (bicyclic 
octapeptides with an indole-( R)-sulfoxide 
bridge), phallotoxins (cyclic heptapeptides with 
an indole/thio-etherbridge), and/or virotoxins 
(heptapeptides have a monocyclic structure, 
this includes 2-methylsulfonyltryptophan 
or 2-methylsulfoxytryptophan and 
dihydroxyproline). • Critically, amatoxins are 
heat stable and not inactivated by cooking. 
• Phallotoxins do not cause poisoning when 
ingested. • The major mode of action is 
inhibition of RNA polymerase II, resulting in 
cell death.
Poisoning
Major toxin is aminohexadienoic acid, which 
produces rapid-onset (latent period of 30 
minutes to 12 hours), fulminant nephrotoxicity.
Poisoning
• Major toxins are orellanine and orelline. 
• Inhibit DNA and RNA polymerases. • A 
typical C. orellanus  mushroom contains 
15–20 mg of orellanine.
Hallucinogenic Mushroom Poisoning
• Major toxins are psilocybin and psilocin; 
psilocybin is a pro-toxin which is metabolized to 
the active toxin psilocin. • Purchased hallucino -
genic mushrooms may be laced with LSD 
(lysergic acid diethylamide), phencyclidine, and/
or ketamine. • Hallucinogenic mushrooms are 
often incorporated into bars of chocolate to aid 
ingestion (the mushrooms often have an 
astringent taste).
Poisoning
• Major toxin is l-(+)-muscarine. • Other 
muscarine enantiomers are commonly present 
but are much less potent and less important 
in cases of poisoning. • l-(+)-Muscarine 
forms a very stable chlorine salt. • Heating, 
boiling, and drying does not inactivate the 
toxin. • Clinical signs reflect muscarinic 
parasympathetic nervous system stimulation 
and a muscarinic cholinergic crisis.
Psychoactive Isoxazole Mushroom 
Poisoning
• Major toxins are ibotenic acid and its 
decarboxylated derivative muscimol. • Act as 
GABA antagonists. • Muscarine is present in 
small amounts. • A. pantherina  may also 
contain amatoxins; however, hepatotoxicity 
with this species appears to be very rare.
Rapid-Onset Myotoxic Mushroom 
Poisoning
• The major myotoxin is cycloprop-2-ene 
carboxylic acid. • A number of other cytotoxic toxins (russuphelins) have been 
identified. • Mushroom also contains a 
gastrointestinal toxin and cadmium.
Poisoning
Major toxins are unknown.
GABA Antagonist Mushroom Poisoning
• Major pro-toxin is gyromitrin. • In the 
digestive tract gyromitrin forms mono -
methylhydrazine, the ultimate toxin. 
• Monomethylhydrazine reacts with 
pyridoxal-5-phosphate forming a hydro -
zone, which decreases glutamic acid 
decarboxylase activity and decreases 
formation of GABA. • Gyromitrin also 
forms methyl- N-formylhydrazine, which is 
hepatotoxic. • Gyromitrin is a carcinogen. 
• Uncooked or partially cooked mushrooms 
have a higher toxicity than fully cooked 
mushrooms (gyromitrin is volatile).
GI Irritant Mushroom Poisoning
A diverse array of toxins is involved but they 
produce clinically similar effects.
Paxillus Syndrome
• Major toxins include involutin (a 
diphenylcyclopenteneone compound). • An 
antigen of an unknown structure in the 
fungus stimulates the formation of IgG 
antibodies in the blood serum. In subsequent 
meals the antigen–antibody complexes are 
formed and become attached to the surface of 
erythrocytes, causing their agglutination and 
Intestine, liver and kidneys; pancreatitis 
reported with A. phalloides ; cellular injury is 
widespread, but typically the liver is the major 
target organ.
Poisoning
Kidneys
Poisoning
Kidneys
• CNS. • Liver, kidneys, and GI systems with 
mistaken ingestion of other toxic species
Poisoning
Muscarinic parasympathetic nervous system.
Poisoning
CNS
Poisoning
Musculoskeletal system.
Poisoning

Canine and Feline, Seventh Edition  917
MMGABA Antagonist Mushroom Poisoning
CNS
GI tract.
• GI tract.
• Erythron.
Worldwide; classically fruiting occurs during 
spring to autumn.
SIGNS
Patients commonly presented with fulminant 
hepatic failure or found dead with fulminant 
hepatic failure of “unknown origin” identified 
during necropsy. The classical clinical course 
occurs over a 7-day period:
• Day 1: Mushroom meal and symptom-free 
interval (6–12 hours). • Day 2: GI phase with 
vomiting, abdominal pain, diarrhea. • Day 3: 
Apparent symptomatic remission, but laboratory 
evidence of developing liver damage. • Day 4: 
Coagulopathy develops and GI bleeding 
commences. • Day 5: Onset of hepatic 
encephalopathy, onset of hepatic coma. • Day 6: 
Renal failure. • Day 7: Death.
Poisoning
• Rapid-onset, acute, fulminant renal failure 
with a 30-minute to 12-hour post-ingestion 
latency period. • Clinical presentation 
resembles nonspecific acute renal failure.
Poisoning
Delayed-onset, acute, fulminant renal failure 
with a 36-hour to 17-day post-ingestion 
latency period.
• Latency is typically 10–30 minutes post 
ingestion. • Clinical signs reflect auditory, 
visual (e.g., biting at invisible flies) or tactile 
hallucinations with the degree of clinical signs 
being dose-dependent. • Most CNS reactions 
are euphoric or excitatory; however, aggression 
can be enhanced in some cases. • Clinical signs 
attributable to anxiety, agitation, and ataxia 
may occur. • Other effects include pupillary 
dilation, nausea, abdominal pain, vomiting, 
yawning, parasthesiae, hyperreflexia, tachy -
cardia, hypertension, cardiac arrhythmias, and 
myocardial ischemic effects. • Convulsions can 
occur, but are more likely in young animals. 
• CNS depression can occur late in the clinical 
course. • For unadulterated mushrooms the 
clinical course is typically less than 1 hour; if 
longer than this ingestion of LSD and/or 
phencyclidine (effects may last >12 hours) 
should be considered. • Beware —ongoing 
convulsive episodes, myocardial ischemia, 
hyperthermia, and rhabdomyolysis are 
possible, particularly with adulterated 
mushrooms.Autonomic Toxicity Mushroom 
Poisoning
• Onset is typically 15 minutes to 2 hours post 
ingestion. • The clinical course is dose-dependent: 
about 2 hours in mild cases and up to 1 day in 
more severe cases. • Remember : DUMBELS—
diarrhea, urination, miosis, bradycardia/
bronchorrhea/bronchoconstriction, emesis, 
lacrimation, and salivation. • Impaired sight 
due to impaired accommodation. • Hypotension, 
vasodilation, and circulatory shock may occur.
Poisoning
• Onset is typically within minutes to 3 hours 
post ingestion. • The typical clinical course is an 
initial period of drowsiness followed by a period of 
manic excitement with visual hallucinations (e.g. 
biting at invisible flies) and bizarre behavior lasting 
up to 48 hours. This is then followed by a period 
of deep CNS depression during which intense 
dreaming has been reported in humans. • Ataxia, 
incoordination, dizziness, mydriasis, myoclonus, 
muscle fasciculation/tremors, hyporeflexia, coma, 
and convulsions (in severe poisoning) can occur. 
• Rarely vomiting and/or diarrhea can occur
Poisoning
• Onset is typically within 2 hours post 
ingestion. • The initial phase (2–24 hours post 
ingestion) consists of acute gastroenteritis which 
may resolve over the next 24 hours. • The later 
phase, developing around 6–12 hours post 
ingestion, consists of muscle pain, myalgias, 
rhabdomyolysis, myoglobinuria, hypertension, 
dehydration, renal failure, hyperkalemia, 
arrhythmias, myocarditis, and cardiovascular 
collapse. • Respiratory failure, acute renal 
failure, pulmonary edema, ventricular 
tachycardia, and circulatory shock have been 
recorded in humans. • In fatal cases, death 
ensues within 12–24 hours post ingestion.
Poisoning
Resembles acute myotoxic poisoning except 
onset is delayed typically for 24 hours with 
resolution over about 15 days in survivors.
• Onset is unpredictable.
• Most cases result in mild, self-limiting GI 
disturbance starting 6–12 hours post 
ingestion. • Cases of severe poisoning may or 
may not present with an initial GI upset 
phase followed by hepatorenal toxicity plus 
neurological disturbance (seizures, mydriasis, 
muscle fasciculations progressing to coma). 
Multiorgan failure is common in severe cases. 
• Methemoglobinemia and hemoglobinuria 
occurs in some cases. • Hydrazines also affect 
the cross-linking of collagen and have been 
associated with dissecting aortic aneurysms.
• Onset is typically 1–3 hours post ingestion. 
• Clinical signs include vomiting, abdominal pain and diarrhea. • Fluid and electrolyte 
disturbances can be severe, particularly in 
small animals. • Disseminated intravascular 
coagulation and renal failure can occur.  
• GI upset is usually short and self-limiting.
• Self-limiting GI upset. • Immune mediate 
hemolytic anemia. • Sensitivity to the 
mushroom builds up with repeated ingestion 
over a period of years.
  DIAGNOSIS
• Early stages—resembles per-acute/acute 
gastroenteritis (fluid loss, hypovolemia, serum 
ion disturbances). • Later stages—typically 
reflect fulminant hepatic failure with massive 
increases in serum liver enzymes, hyperbili -
rubinemia, and coagulopathy.
Poisoning
Reflects acute oliguric/anuric renal failure 
following acute renal tubular necrosis.
Poisoning
Poisoning
Poisoning
Poisoning
• Serum chemistry results may reflect acute 
renal failure with massively elevated serum 
creatine kinase; other serum chemistry changes 
may include increased lactate dehydrogenase 
and increased transaminases. • Hyperkalemia 
and hypocalcemia are often prominent. 
• Urinalysis may indicate myoglobinuria.
Poisoning
As per rapid-onset myotoxic mushroom 
• CBC may indicate oxidative damage to 
erythrocytes (e.g., Heinz body formation) and 
hemolysis. • Methemoglobinemia is present in 
some cases. • Evidence of liver damage 
(increased serum transaminases) may occur in 
some cases. • Hyper- and hypoglycemia can 
occur. • Hypovolemia and serum ion (continued)  Mushroom Toxicoses

918  Blackwell’s Five-Minute Veterinary Consult  
Mabnormalities may occur following GI damage. 
• Coagulopathies occur in some cases.
Reflect fluid loss and serum ion disturbances.
Reflect fluid loss and serum ion disturbances 
and immune-mediated anemia.
Uneaten mushrooms should be placed in a dry 
paper bag for transport to an expert mycologist.
Identification of uneaten mushrooms or spores 
in gastric contents by an experienced mycologist
• Meixner test is unreliable. • Serum and 
urine amatoxins have no clinical value.
Poisoning
Aminohexadienoic acid determination in body 
fluids and kidney is possible but rarely performed.
Poisoning
In renal biopsy tissue, orellanine is detectable 
by thin-layer chromatography up to 6 months 
after poisoning.
Psilocybin and psilocin can be measured in 
blood, plasma, serum, and urine; detection 
period in urine is typically about 3 days.
Poisoning
Response to low-dose treatment with atropine 
can be considered.
Poisoning
Poisoning
Poisoning
GABA Antagonist Mushroom  
Poisoning
Nonspecific.
  TREATMENT
• Early euthanasia in confirmed cases should 
be considered. • Cases of suspect ingestion should be hospitalized for observation for at 
least 3–4 days.
Poisoning
Cases of suspect ingestion should be hospitalized 
for observation for at least 3–4 days
Poisoning
Cases of suspect ingestion require careful and 
repeated assessment of renal status for up to 
17 days.
Cases of suspect ingestion should be 
hospitalized for observation.
Poisoning
Poisoning
Poisoning
be considered. • Cases of suspect ingestion 
should be hospitalized and may require 
urgent treatment.
Poisoning
Poisoning
• Observation, fluid resuscitation, and 
electrolyte replacement as required. • If a 
confirmed case presents within 1-4 hours post 
ingestion (very unusual), gastric lavage and 
oral activated charcoal treatment (for up to 
the first 36 hours) could be considered. 
• Hemoperfusion and plasmapheresis are 
ineffective. • Therapeutic total plasma 
exchange could be considered.
Poisoning
• If a confirmed case presents within 1–4 
hours post ingestion (very unusual), gastric 
lavage could be considered. • T reatment as 
per any form of acute renal failure.Delayed Nephrotoxic Mushroom 
Poisoning
• Given the long latency period, patients are 
unlikely to be presented early enough for GI 
decontamination to be of any benefit. 
• T reatment as per any form of acute renal 
failure.
• Simple supportive care consisting of 
placement in a dark, quiet room with the 
owner is often effective for simple hallucino-
genic mushroom poisoning. • Beware —risk 
of self-injury is present.
Poisoning
lavage and/or single-dose activated charcoal 
treatment could be considered. • Careful 
hemodynamic and electrocardiographic 
monitoring is recommended. • Fluid 
resuscitation and careful electrolyte monitoring 
may be required if diarrhea is severe.
Poisoning
• T reatment is primarily supportive. 
• Placing in a dark, quiet environment in the 
presence of the owner may be helpful. 
• Beware —risk of self-injury is present.
Poisoning
treatment could be considered. • Fluid 
resuscitation and careful electrolyte 
monitoring and management is required.
Poisoning
Fluid resuscitation and careful electrolyte 
monitoring may be required.
monitoring are the mainstays of treatment.
ACTIVITY
As needed and clinically justifiable.
• There are no specific antidotes. • Silibinin 
(20–40 mg/kg/day in divided doses) may have Mushroom Toxicoses  (continued)

Canine and Feline, Seventh Edition  919
Mlimited value. • Penicillin G (300,000–1 million 
U/kg/day) may have limited value. • IV glucose 
during hepatic failure phase. • Fresh frozen 
plasma and vitamin K if coagulopathy is present.
Poisoning
As per any form of acute renal failure.
Poisoning
• For severe reactions, longer acting benzo -
diazepines such as diazepam may be useful. 
• Convulsions can be managed by the use of 
barbiturates. • Beware —reactions lasting 
longer than an hour or so may indicate LSD, 
ketamine, or phencyclidine poisoning.
Poisoning
• Mild cases may not require drug treatment. 
• In moderate to severe cases the drug of choice 
(and antidote) is atropine administered slowly 
and carefully to effect (the key clinical endpoint 
is the drying of respiratory secretions, not pupil 
size). • Fluid resuscitation and careful electrolyte 
monitoring may be required if diarrhea is severe.
Poisoning
• Typically monitoring and prevention of 
self-injury is sufficient. • Benzodiazepines 
such as diazepam could be considered during 
the manic phase.
Poisoning
• Nonspecific symptomatic and supportive care 
is required. • The major priorities are fluid and 
electrolyte management. • Dantrolene could be 
Poisoning
• Pyridoxine (vitamin B6) can be used as an 
“antidote” in treatment of convulsions or coma 
at about 25 mg/kg IV over 15–20 minutes. 
• Methylene blue 1 mg/kg IV over 5–30 
minutes; if the methemoglobin level remains 
greater than 30% or if symptoms persist, a 
repeat dose of 1 mg/kg IV may be given 1 hour 
after the first dose; if methemoglobinemia does 
not resolve after 2 doses, consider alternative 
interventions if methemoglobinemia is clinically 
significant. • Benzodiazepines and barbiturates 
may be useful if CNS excitation is present.
Mainstay of treatment is fluid resuscitation 
and electrolyte management.
and electrolyte management.  FOLLOW-UP
• Survival is unlikely following clinically 
significant ingestions. • Survivors of 
fulminant liver failure require ongoing 
monitoring of liver and kidney functions and 
monitoring of the coagulation system.
Poisoning
• Survival is possible. • Ongoing monitoring 
of renal function is recommended.
Poisoning
Risk of reexposure if owners are consumers of 
hallucinogens.
Poisoning
Outcome is typically good when supportive 
care is provided.
Poisoning
Poisoning
• Survival is rare. • Severe muscle damage is 
likely in survivors.
Poisoning
• Poisoning is often severe.
• Multiorgan failure (primary, or secondary 
to hemolysis or hepatorenal failure) occurs in 
GI damage can be severe, but recovery is 
usual.
• GI damage is typically mild and self-
limiting. • Require monitoring for immune 
mediated anemia.
Prevent dogs roaming, control mushrooms in 
areas where animals are kept.
Survival following clinically significant 
ingestion is unlikely; the major determinant 
of survival is the amount of amatoxins 
ingested.Primary Acute Nephrotoxic Mushroom 
Poisoning
• Poorly documented in veterinary species. 
• Survival is possible with appropriate 
Poisoning
Prognosis is typically good provided 
misadventure is prevented.
Poisoning
Prognosis is typically good with symptomatic 
and supportive care.
Poisoning
Poisoning
Survival is rare.
Poisoning
• Many cases are mild. • Evidence of 
hepatorenal failure indicates a poor prognosis.
Prognosis is reasonable provided reexposure 
to the mushrooms does not reoccur.
Young animals or animals that are inexperi-
enced with a specific location are possibly 
more likely to be poisoned.
SYNONYMS
Mushroom poisoning; shroom poisoning.
http://www.toxinology.com/index.cfm
Author  Rhian Cope
Consulting Editor  Lynn R. Hovda(continued)  Mushroom Toxicoses

920  Blackwell’s Five-Minute Veterinary Consult  
MMyasthenia Gravis
  BASICS
A disorder of neuromuscular transmission 
characterized by muscular weakness and 
excessive fatigability.
T ransmission failure at the neuromuscular 
junction—results from structural or 
functional abnormalities of the nicotinic 
acetylcholine receptors (AChRs) or other 
end-plate proteins and enzymes (congenital 
form) and from autoantibody-mediated 
destruction of AChRs and postsynaptic 
membranes (acquired form).
• Neuromuscular—result of abnormalities or 
destruction of AChRs, choline acetyltransferase 
or end-plate cholinesterase.
• Respiratory—may find aspiration 
pneumonia secondary to megaesophagus.
GENETICS
• Congenital familial forms—Jack Russell 
terrier, springer spaniel, smooth fox terrier; 
smooth-haired miniature dachshund, Gammel 
Dansk hønsehund, Labrador retriever; 
autosomal recessive mode of inheritance.
• Acquired—as with other autoimmune 
diseases, requires appropriate genetic 
background for disease to occur; multi -
factorial, involving environmental, infectious, 
and hormonal influences.
• Familial forms of acquired myasthenia 
gravis (MG) occur in the Newfoundland and 
Great Dane breeds.
• Congenital—rare.
• Acquired—not uncommon in dogs; 
Worldwide
Species
• Congenital—Jack Russell terriers; springer 
spaniels; smooth fox terriers; smooth-haired 
miniature dachshunds, Gammel Dansk 
hønsehund. Labrador retriever.
• Acquired—several breeds: golden retrievers; 
German shepherd dogs; Labrador retrievers; 
dachshunds; Scottish terriers; Akitas; and 
Abyssinian and Somali cats.
• Congenital—6–8 weeks of age.
• Acquired—bimodal age of onset; dogs: 1–4 
years of age and 9–13 years of age.
• Congenital—none.• Acquired—may be a slight predilection for 
females in the young age group; none in the 
old age group.
SIGNS
• Acquired—may have several clinical 
presentations ranging from focal involvement 
of the esophageal, pharyngeal, and extraocular 
muscles to acute generalized collapse.
• Should be on the differential diagnosis of 
any dog with acquired megaesophagus, lower 
motor neuron weakness, or a cranial 
mediastinal mass.
• Regurgitation—common; important to 
differentiate between vomiting and 
• Voice change.
• Exercise-related weakness.
• Acute collapse.
• Progressive weakness.
• Sleep with eyes open.
• Patient may look normal at rest.
• Excessive drooling, regurgitation, and 
repeated attempts at swallowing.
• Muscle atrophy—usually not found.
• Dyspnea—with aspiration pneumonia.
• Fatigue or cramping—with mild exercise.
• Careful neurologic examination—subtle 
findings: decreased or absent palpebral reflex 
(may be fatigable); may note a poor or absent 
gag reflex; spinal reflexes usually normal but 
fatigable (rarely absent and dog unable to 
support its weight).
• Ventroflexion of the neck (cats, uncommon 
in dogs).
CAUSES
• Immune-mediated.
• Paraneoplastic.
• Appropriate genetic background.
• Neoplasia—particularly thymoma.
• Methimazole treatment (cats)—may result 
in reversible disease.
• Vaccination can exacerbate active MG.
• Intact female.
  DIAGNOSIS
• Other disorders of neuromuscular 
transmission—tick paralysis; botulism; 
cholinesterase toxicity.
• Acute or chronic polyneuropathies.
• Polymyopathies—including polymyositis.
• Diagnosis depends upon a careful history, 
thorough physical and neurologic examinations, 
and specialized laboratory testing.CBC/BIOCHEMISTRY/URINALYSIS
• Normal.
• Serum creatine kinase activity—usually 
normal; may be elevated if MG is 
associated with polymyositis and 
concurrent thymoma.
• Serum AChR antibody titer—diagnostic 
for acquired form.
• Thyroid and adrenal function—may see 
abnormalities associated with acquired form.
IMAGING
Thoracic radiographs—megaesophagus; cranial 
mediastinal mass, aspiration pneumonia.
• Ultrasound-guided biopsy of cranial 
mediastinal mass—may support diagnosis of 
thymoma.
• Dramatic increase in muscle strength after 
administration of edrophonium chloride 
0.1 mg/kg IV—may see false-negative and 
false-positive responses.
• Decreased or absent palpebral reflex—may 
return after edrophonium chloride admini  - 
stration.
• Electrophysiologic evaluation—necessity 
questionable with increased availability of 
AChR antibody testing; many patients with 
acquired form are poor anesthetic risks.
• Electrocardiogram—with bradycardia; 
third-degree heart block has been documented 
in some patients with acquired disease.
Biopsy of a cranial mediastinal mass may 
reveal thymoma, thymic hyperplasia, or 
thymic atrophy.
  TREATMENT
• Inpatient—until adequate dosages of 
anticholinesterase drugs are achieved.
• Aspiration pneumonia—may require 
intensive care.
• Gastrostomy tube—may be required if 
patient is unable to eat or drink without 
significant regurgitation.
• Oxygen therapy, intensive antibiotic 
therapy, IV fluid therapy, and supportive 
care—generally required for aspiration 
• Nutritional maintenance with a 
gastrostomy tube—multiple feedings of a 
high-caloric diet; good hygiene care.
• Elevation of food and water.
ACTIVITY
Self-limited owing to the severity of muscle 
weakness and extent of aspiration 

Canine and Feline, Seventh Edition  921
MDIET
May try different consistencies of food—
gruel; hard food; soft food; evaluate what is 
best tolerated.
• Warn client that, although the acquired 
disease is treatable, most patients require 
months of special feeding and medication.
• Inform client that a dedicated owner is 
important to a favorable outcome for 
acquired myasthenia.
• Prognosis is poor for congenital myasthenic 
syndrome.
• Cranial mediastinal mass—thymoma.
• Before attempting surgical removal, stabilize 
patient with anticholinesterase drugs and treat 
• Weakness may not be clinically evident initially.
• Suspected thymoma—test all patients for 
acquired MG before surgery.
• Anticholinesterase drugs—prolong the 
action of acetylcholine at the neuromuscular 
junction; pyridostigmine bromide tablets or 
syrup (Mestinon syrup, diluted half and half 
in water) at 1–3 mg/kg PO q8–12h.
• Corticosteroids 0.5 mg/kg q24h; initiated if 
there is a poor response to pyridostigmine or 
if there is no response to the edrophonium 
chloride challenge.
Avoid drugs that may reduce the safety 
margin of neuromuscular transmission— 
aminoglycoside antibiotics; antiarrhythmic 
agents; phenothiazines; anesthetics; narcotics; 
muscle relaxants; magnesium.
• Avoid large volumes of barium for 
evaluating megaesophagus.
• Large air-filled esophagus seen on survey 
radiographs—barium study not indicated.
• Avoid immunosuppressive dosages of 
prednisone—may worsen muscle weakness.
• Avoid unnecessary vaccinations.
• Azathioprine 2 mg/kg PO through 
gastrostomy tube q24h. Taper to q48h when 
clinical remission of the disease.
• Mycophenolate 20 mg/kg PO q12h. 
Reduce dosage by 50% once significant 
improvement or resolution of clinical signs is 
noted.
  FOLLOW-UP
• Return of muscle strength should be 
evident.
• Thoracic radiographs—evaluated every 4–6 
weeks for resolution of megaesophagus.
• AChR antibody titers—evaluated every 
8–12 weeks; decrease to the normal range 
with immune remission.
N/A
• Respiratory arrest.
• No severe aspiration pneumonia or 
pharyngeal weakness—good prognosis for 
complete recovery; resolution usually within 
6–8 months.
• Thymoma present—guarded prognosis 
unless complete surgical removal and control 
of myasthenic signs are achieved.
• Other autoimmune disorders—thyroiditis; 
skin disorders; hypoadrenocorticism, thrombo  - 
cytopenia, hemolytic anemia, inflammatory 
• Disorders of the thymus—thymoma; 
thymic hyperplasia.
• Other neoplasias.
Bimodal age of onset—1–4 years of age and 
9–13 years of age.
• In humans, weakness may improve during 
pregnancy but worsens after delivery; some 
neonates of affected mothers have a 
temporary MG-like weakness that lasts several 
days to weeks that is due to in utero  transfer 
of autoantibodies from the mother.
• Documented in dogs after whelping.
SEE ALSO
• Chapters covering autoimmune diseases.
• AChR = acetylcholine receptor.
Comparative Neuromuscular Laboratory: 
http://vetneuromuscular.ucsd.edu
Khorzad R, Whelan M, Sisson A, Shelton 
GD. Myasthenia gravis in dogs with an 
emphasis on treatment and critical care 
management. Vet Emerg Crit Care 2011, 
21:193–208.
Megaesophagus. Compend Contin Edu Vet 
2012, 34:E1–8.
Shelton GD. Myasthenia gravis and disorders 
of neuromuscular transmission. Vet Clin 
North Am 2002, 31:189–200.
Shelton GD. Routine and specialized 
laboratory testing for the diagnosis of 
neuromuscular diseases in dogs and cats. 
Vet Clin Pathol 2010, 39:278–295.
Shelton GD. T reatment of autoimmune 
myasthenia gravis. In: Bonagura JD, T wedt 
DC, eds., Current Veterinary Therapy XIV. 
Philadelphia, PA: Saunders, 2009, pp. 
1108–1111.
Shelton GD, Lindstrom JM. Spontaneous 
remission in canine myasthenia gravis: 
implications for assessing human MG 
therapies. Neurology 2001, 57:2139–2141.
Author  Lauren Talarico
acknowledge the prior contribution of G. 
Diane Shelton.
available online(continued)  Myasthenia Gravis

922  Blackwell’s Five-Minute Veterinary Consult  
MMycobacterial Infections
  BASICS
OVERVIEW
• Mycobacteria—Gram-positive, acid-fast 
higher bacteria (genus Mycobacterium ); 
obligate or sporadic pathogens in humans and 
animals.
• T uberculosis—rare in dogs and cats.
• Leprosy:
◦ Cats—two syndromes.
◦ Dogs—canine leproid granuloma 
syndrome.
• Systemic or noncutaneous infection with 
nontuberculous mycobacteria.
• Cutaneous/subcutaneous infections due to 
rapidly growing mycobacteria (e.g., myco -
bacterial panniculitis):
◦ Dogs and cats—caused by saprophytic 
mycobacteria.
• Systems affected—respiratory, skin/
exocrine; determined by cause.
Tuberculosis
• Cats and dogs of any age.
• Basset hound and Siamese cat reported as 
possibly more susceptible.
Feline Leprosy
• Syndome 1—free-roaming kittens and 
young adult cats.
• Syndrome 2—older cats (average 9 years).
Canine Leproid Granuloma
Shorthaired outdoor-housed large-breed dogs, 
especially boxers and German shepherd dogs.
Systemic Nontuberculous 
Mycobacteriosis
Sporadic disease that can affect dogs and cats 
of any age.
Mycobacterial Panniculitis
Adult dogs and cats.
SIGNS
• Organism— Mycobacterium tuberculosis  
(humans), M. bovis  (cattle, wild mammals), 
and M. microti  (voles), and M. microti -like.
• Dogs and cats exposed to infected primary 
hosts sporadically infected.
• Disseminated or multiorgan disease caused 
by intracellular facultative organism.
• Correlated with the route of exposure.
• Major sites of involvement—oropharyngeal 
lymph nodes, cutaneous and subcutaneous 
tissues of the head and extremities; pulmonary  
system; gastrointestinal system.
• Dogs—respiratory, especially coughing.
• Cats—from contaminated milk: weight 
loss, chronic diarrhea, and thickened 
intestines; from predation: cutaneous 
nodules, ulcers, and draining tracts.
• Most dogs and many cats—pharyngeal and cervical lymphadenopathy; unproductive 
vomiting, ptyalism, or tonsillar abscess; 
lymphadenopathy; may ulcerate and drain.
• Pyrexia.
• Anorexia and weight loss.
• Hypertrophic osteopathy or hypercalcemia.
• Disseminated disease—body cavity 
effusion; visceral masses; bone or joint lesions; 
dermal and subcutaneous masses and ulcers; 
lymphadenopathy and/or abscesses; CNS 
signs; sudden death.
• Organisms— M. lepraemurium  (from 
rodents) and two unnamed leprosy organisms 
(M. visibilis  [provisional]).
• Syndrome 1— M. lepraemurium : young cats 
with localized nodular disease, affecting limbs 
with sparse to moderate numbers of acid-fast 
bacilli present in lesions initially; progress 
rapidly, may ulcerate; aggressive clinical 
course; recurrence after surgical excision; 
widespread lesions develop in several weeks.
• Syndrome 2—unnamed species with 
affinity to M. malmoense : older cats with 
generalized skin lesions and large numbers of 
acid-fast bacilli in lesions; initial skin nodules 
that do not ulcerate, progressive over months 
to years.
• Feline multisystemic granulomatous 
mycobacteriosis—diffuse cutaneous 
thickening and multiple organ involvement.
• Organism— Mycobacterium  sp. Murphy 
identified by DNA sequencing.
• Well-circumscribed painless nodules 
(2 mm–5 cm) in dermis or subcutis; head or 
ear, but may be anywhere on the body; only 
large lesions ulcerate.
• No systemic signs of illness.
• Organisms— M. chelonae-abscessus  group, 
M. avium  complex, M. fortuitum , M. genavense , 
M. kansasii , M. massiliense , M. simiae , 
M. smegmatis , M. thermoresistable , M. xenopi .
• Sporadic infections in dogs and cats; 
associated in patients with concurrent disease 
immunosuppression or as a result of traumatic 
tissue introduction of saprophytic organism; 
syndromes include pleuritis, granulomas, 
disseminated disease, neuritis, or broncho  - 
• Pulmonary and systemic infections with 
atypical mycobacteriosis are rare in dogs, in 
which case the signs are as for tuberculosis.
• M. avium  infection—disease most often 
disseminated.
• Organisms— M. fortuitum  group, 
M. chelonae-abscessus  group, M. smegmati  
groups, M. phlei , M. terrae  complex, 
M. thermoresistable , M. ulcerans .• Cutaneous—traumatic lesion that fails to 
heal with therapy; spreads locally in the 
subcutaneous tissue (panniculitis); original 
lesion enlarges, forming a deep ulcer that 
drains hemorrhagic exudate; surrounding 
tissue becomes firm; satellite pinpoint 
ulcerations open and drain.
• Wound dehiscence at surgery sites.
• Source of exposure—always an infected 
typical host.
• Dogs—usually from an infected person in 
the household ( M. tuberculosis ); route is 
ingestion of expectorated infectious material; 
aerosol exposure; patients often found in 
urban areas with newly arrived immigrants.
• Cats—classically exposed by drinking 
unpasteurized milk of infected cattle ( M. bovis ); 
much less common now; may be exposed by 
predation on infected small mammals 
(M. bovis , undefined tuberculosis species).
• Syndrome 1—cases have been reported 
from temperate coastal areas and port cities; 
cool climate may facilitate growth of the 
organism in extremities.
• Syndrome 2—cases are from rural environ -
ments; old age or immune-incompetence may 
be a risk factor; exact risk factors remain 
undefined; exposure to rodents postulated.
• Associated with fly bites and may fluctuate 
seasonally; short coats may predispose.
• Disease likely to be worldwide; most cases 
reported from Australia, Asia, and Brazil.
• In the United States, reported in California, 
Hawaii, and Florida.
• Patients are immunosuppressed or have 
concurrent systemic disease.
• Routes of exposure in pulmonary and 
systemic disease are uncertain.
• Infections usually have antecedent trauma 
or surgical wound; most patients are immune-  
competent.
• T rauma and accidental inoculation of the 
subcutaneous fat results in infection; history 
of bite wound possible (subcutaneous 
disease).
• Overweight of obese animals are more at 
risk.
  DIAGNOSIS
• All manifestations—fungal and other 
actinomycotic infections.

Canine and Feline, Seventh Edition  923
M• Panniculitis: nocardiosis.
T uberculosis (dogs)—intradermal skin testing 
with PPD (purified protein derivative) or 
BCG (bacillus Calmette–Guérin) on inner 
pinna; may produce false-positive.
IMAGING
• Thoracic, abdominal, or skeletal lesions—
suggest granulomatous infectious disease.
• No specific lesions for the mycobacterioses.
• Pulmonary tuberculosis lesions—may 
become calcified or cavitated.
• Biopsy material from affected tissue.
• Aspiration of purulent material—used for 
microbiological identification; ultrasound-
guided aspiration techniques may be 
• Biopsy specimens—sterile collection; 
incorporate center of a granulomatous focus.
• Exudate from infected tissues—detection 
with acid-fast carbolfuchsin or auramine-
rhodamine fluorochromes; on routine staining, 
organisms are negatively stained, showing 
“ghosts” of bacilli within macrophages;  
swabs or aspirations of draining cutaneous 
lesions or lymph nodes, transtracheal wash; 
endoscopic brushings; rectal cytology; 
impressions taken at surgical biopsy; 
heat-fixed exudate should be submitted with 
tissue for culture.
• Culture—special media and techniques 
required; referral to specialized laboratories 
may be required for nontuberculous 
• PCR methodologies—useful for any of the 
mycobacterial infections using tissue 
specimens or fluids; for canine leproid 
granuloma and the two feline leprosy 
syndromes, primers are not commercially 
available, but can be used to identify the 
suspect organisms.
  TREATMENT
TUBERCULOSIS
• Obtain permission of health authorities in 
cases of M. tuberculosis  infection; zoonotic 
potential should be considered.
• Multiple agent chemotherapy with drugs 
used to treat human tuberculosis have been 
successful; M. avium  complex infections are 
difficult to treat.Feline Leprosy
• Individual lesions may be excised with 
aggressive margins.
• Surgical treatment should be preceded by 
systemic therapy.
Excision is curative; lesions may self-cure; 
antimicrobial therapy may assist healing.
Subcutaneous and Systemic 
Nontuberculous Infections
• T reatment should be based on organism 
identification and antibiotic sensitivity testing.
• Multiple drug therapy is often warranted.
• Aggressive surgical debulking may aid 
resolution; antimicrobial therapy pre- and 
intraoperatively is recommended.
• Multidrug oral therapy mandatory.
• Current recommendation—
fluoroquinolones, clarithromycin, and 
doxycycline for 6–9 months.
• Marbofloxacin 5.5 mg/kg PO q24h, 
pradofloxacin 5–7.5 mg/kg PO q24h.
• Clarithromycin 5–10 mg/kg PO q24h.
• Isoniazid and rifampin—combinations have 
been used; single report of use in cats.
• Isoniazid 10–20 mg/kg (up to 300 mg 
total) PO q24h.
• Ethambutol 15 mg/kg PO q24h.
• Pyrazinamide—instead of ethambutol 
15–40 mg/kg PO q24h.
• Pradofloxacin 5–7.5 mg/kg PO q24h.
• In vitro  sensitivity testing may be used to 
choose chemotherapy.
• Antibiotics reported to be effective: 
macrolide, trimethoprim-potentiated 
sulfonamide, tetracycline, aminoglycoside, 
and fluoroquinolone antibiotics.
• Antituberculosis drugs are not generally effective.
• Single-agent therapy not recommended due 
to poor long-term response; double-agent 
therapy recommended.
• Long-term therapy should be based on 
sensitivity testing.
• T reatment should be continued for 2–6 
months.
• Relapses are common.  FOLLOW-UP
• Antituberculosis and antileprosy drugs—
examine monthly; monitor for anorexia and 
• Liver profile monthly.
• Instruct owners to report cutaneous lesions 
Guarded; but undefined as experience with 
modern drugs is limited.
• Guarded to poor—syndrome 1.
• Fair—syndrome 2, especially if lesions are 
amenable to surgical excision.
Good
Relapses are common; aggressive surgical 
approaches and multiple drug therapy may 
improve outlook.
• T uberculosis—reverse zoonosis possible.
• Affected domestic pets are potential serious 
zoonotic threats to owners; do not attempt 
treatment without agreement of public health 
authorities.
• M. tuberculosis —greatest potential for 
zoonosis, especially with draining cutaneous 
lesions.
• Disease transmission from dogs and cats to 
humans—rarely recorded.
Malik R, Smits B, Reppas G, et al. Ulcerated 
and nonulcerated nontuberculous cutane-
ous mycobacterial granulomas in cats and 
dogs. Vet Dermatol 2013, 24(1):146–153.
e32–33.
O’Halloran C, Gunn-Moore DA. 
Mycobacteria in cats: an update. In Pract 
2017, 39(9):399–406.
Resnick(continued)  Mycobacterial Infections

924  Blackwell’s Five-Minute Veterinary Consult  
MMycoplasmosis
  BASICS
• Class Mollicutes.
• Divided into hemotropic (formerly 
Haemobartonella and Eperythrozoon, see: 
Hemotropic Mycoplasmosis) and nonhemo­
tropic types (discussed here).
• More than 80 genera, three families: 
Mycoplasmas, Ureaplasmas, and 
Acholeplasmas.
• Smallest (0.2–0.3 μm) and simplest 
prokaryotic cells capable of self‐replication.
• Fastidious, facultative anaerobic, Gram‐
negative rods.
• Lack cell wall; thus plastic, highly 
pleomorphic, fragile and sensitive to lysis by 
osmotic shock, detergents, alcohols, and 
specific antibody plus complement. Enclosed 
by a trilayered cell membrane built of 
amphipathic lipids and proteins; therefore 
resistant to lysozyme and cell wall‐inhibiting 
antibacterials; most require sterols for growth.
• Reproduce by binary fission; genome 
replication not necessarily synchronized with 
cell division, resulting in budding forms and 
chains of beads.
• Small genome (0.6–1.6 Mb), believed to be 
result of reductive evolution from a common 
Gram‐positive ancestor adapting to obligate 
parasitic life.
• Ubiquitous in nature as parasites, 
commensals, or saprophytes in animals, 
plants, and insects; many are pathogens of 
humans, animals, plants, and insects.
• Often part of the resident flora as 
commensals on mucous membranes of the 
upper respiratory, digestive, and genital tracts; 
pathogenicity and role in disease often 
• Species show considerable host specificity.
• Mechanisms by which disease is caused are 
poorly understood.
• Some species attach to cells by specific 
receptors; small size and plastic nature enable 
them to adapt to the shape and contours of 
host cell surfaces.
• Intimate contact with host cells—necessary 
for assimilation of vital nutrients and growth 
factors which organism cannot synthesize. 
This, along with the tendency of exogenous 
proteins to bind to mycoplasmal membrane 
may allow organism to evade the host’s 
immune response. May incorporate host cell 
antigen onto mycoplasma membrane 
(capping) because of lack of cell wall. 
Conversely, mycoplasmal protein antigen may 
become incorporated onto surface of host 
cell, involving host cell in deleterious 
immunologic reactions intended against the 
organism.• Products produced during growth—
capsular carbohydrate, hemolysins, 
proteolytic enzymes, ammonia, and 
endonucleases; accumulation of Mycoplasma  
metabolites (i.e., H2O2, NH3) may contribute 
to cytopathic effects and tissue damage; 
cytotoxic glycoproteins and proteins have 
been isolated from the membranes of several 
species.
• Immune response—predominantly 
humoral; as with bacterial infections, IgM 
and IgA are first antibodies to appear, 
followed by IgG.
• Fibrinous exudate accompanying 
infections—protects organism from 
antibodies and antimicrobial drugs; 
contributes to chronicity.
• Secondary bacterial invaders—common (e.g., 
attachment to respiratory tract cells results in 
destruction of cilia, which predisposes patient 
to secondary bacterial infection).
• Sialidase, a virulence factor that promotes 
colonization, tissue invasion, and damage to 
host cells—varies in expression among strains 
of canine mycoplasma species.
Dogs
• Gastrointestinal—associated with colitis.
• Musculoskeletal—arthritis; from 
Mycoplasma spumans .
• Renal/urologic—urinary and genital tract 
infections (e.g., balanoposthitis, urethritis, 
prostatitis, cystitis, nephritis, vaginitis, 
endometritis); caused by M. canis  and M. 
spumans .
• Reproductive— Mycoplasma  and Ureaplasma ; 
associated with infertility, early embryonic 
death, abortion, stillbirths or weak newborns, 
and neonatal mortality.
• Respiratory—pneumonia and upper 
respiratory infections; caused by M. cynos ; 
associated with M. canis , M. spumans , M. 
edwardii , M. feliminutum , M. gateae , and M. 
bovigenitalium .
• Nervous—meningitis, associated with M. 
edwardii .
Cats
• Musculoskeletal—chronic fibrinopurulent 
polyarthritis and tenosynovitis; associated 
with M. gateae  and unspecified mycoplasmal 
• Ophthalmic—conjunctivitis; associated 
with M. felis  (5–25%).
• Renal/urologic—urinary tract infections.
• Reproductive—abortions and fetal deaths; 
associated with M. gateae  and ureaplasmas.
• Respiratory—pneumonia, associated with 
M. gateae , M. feliminutum , and M. felis ; 
upper respiratory infections, associated with 
M. felis .
• Skin/exocrine—chronic cutaneous abscesses.
• Nervous—meningoencephalitis, associated 
with M. felis .INCIDENCE/PREVALENCE
• Frequent inhabitants of mucosal 
membranes; M. gateae  and/or M. felis  found 
in oral cavity or urogenital tract of 70–80% 
of healthy cats.
• Rate of isolation in diseased dogs much 
higher than in normal dogs.
Ubiquitous
Species
All ages.
SIGNS
Pathogenic role controversial, can be 
identified in asymptomatic animals.
• Polyarthritis—chronic intermittent 
lameness; reluctance to move; joint pain.
• Fever.
• Malaise.
• Conjunctivitis—unilateral or bilateral.
• Cough.
• Polyarthritis—diffuse limb edema, joint 
swelling, pain.
• Conjunctivitis—blepharospasm; chemosis, 
conjunctival hyperemia, epiphora, and serous 
or purulent ocular discharge.
• Mild rhinitis—sneezing.
CAUSES
• Mycoplasma  flora of dogs— M. canis , M. 
spumans , M. maculosum , M. edwardii , M. 
cynos, M. molare , M. opalescens , M. felis , M. 
feliminutum , M. gateae , M. arginini , M. 
bovigenitalium , M. mucosicanis , Acholeplasma 
laidlawii , and ureaplasmas.
• Mycoplasma  flora of cats— M. felis , M. 
gateae , M. feliminutum , M. arginini , M. 
pulmonis , M. arthritidis , M. gallisepticum , 
Acholeplasma laidlawi , and ureaplasmas.
• Commensals—occasionally cause systemic 
infection associated with immunodeficiency, 
immunosuppression, or cancer.
• Impaired resistance of the host—may allow 
organism to cross the mucosal barrier and 
disseminate (e.g., primary ciliary dyskinesia).
• Organism may be opportunistic—one 
factor in a multifactorial causal complex (e.g., 
impaired pulmonary clearance from viral 
infection may allow organism to establish 
infection in lungs as secondary opportunistic 
pathogen).
• Predisposing factors—stresses (e.g., 
reproductive problems associated with 
overcrowded operations) and other factors 
(e.g., urinary tumors and urinary calculi).

Canine and Feline, Seventh Edition  925
M  DIAGNOSIS
• Upper respiratory infection (dogs and 
cats)—viruses (parainfluenza virus, canine 
distemper, canine influenza virus, herpesvirus, 
feline calcivirus, reovirus); Chlamydia psittaci ; 
bacteria ( Bordetella bronchiseptica , 
staphylococci, streptococci, coliforms).
• Urinary tract infection (dogs and cats)—
bacteria (staphylococci, streptococci, 
coliforms); fungus ( Candida ); parasites.
• Infertility, early embryonic death, abortion, 
stillbirths or weak newborns, and neonatal 
mortality (dogs)—bacteria ( Brucella , 
Salmonella , Campylobacter , E. coli , 
Streptococcus ); viruses (canine herpesvirus, 
canine distemper, canine adenovirus); 
Toxoplasma gondii ; endocrinopathies 
(progesterone deficiency, hypothyroidism).
• Prostatitis (dogs)—bacteria ( E. coli, Brucella 
canis); fungi ( Blastomyces, Cryptococcus ).
• Arthritis (dogs and cats)—immune‐
mediated; bacteria (staphylococci, 
streptococci, coliforms, anaerobes); L‐form 
bacteria; Rickettsia  (Ehrlichia ); Borrelia 
burgdorferi ; fungi ( Coccidioides , Cryptococcus , 
Blastomyces ); protozoa ( Leishmania ); viruses 
(feline calicivirus).
• Conjunctivitis (cats)—feline herpesvirus; 
feline calicivirus; feline reovirus; Chlamydia 
psittaci ; bacteria.
With Polyarthritis
• Hypoglobulinemia.
• Proteinuria, resulting from immune‐
complex glomerulonephritis.
• Difficult to demonstrate in and from 
tissues.
• PCR of 16S rRNA.
◦ PCR denaturing gradient gel electro­
phoresis (PCR‐DGGE)—used to identify 
difficult‐to culture or difficult‐to‐differentiate 
• Fluorescent antibody test—definitive 
diagnosis; isolate and identify or detect the 
organism in tissues:
◦ Submit cotton swabs placed in Hayflick 
broth medium or commercially available 
swabs; organisms fragile; refrigerate specimens 
and deliver to the laboratory within 48 hours; 
freeze (−80°C) to preserve longer.• Extremely pleomorphic—in smears (e.g., 
conjunctival scrapings) seen as coccobacilli, 
coccal forms, ring forms, spirals, and 
filaments.
• Stains—stain poorly (Gram‐negative); 
preferred: Giemsa or other Romanowsky 
stain.
• Culture—fastidious, require complex 
growth media; form microcolonies having 
characteristic “fried egg” appearance.
IMAGING
Polyarthritis—no radiographic changes.
• Arthrocentesis—polyarthritis, high 
numbers of nondegenerative neutrophils in 
synovial fluid.
• Prostatic wash/urine —inflammatory cells 
with negative routine bacterial culture.
• T ranstracheal or endotracheal wash—high 
numbers of nondegenerate neutrophils with 
no organisms seen.
  TREATMENT
• Doxycycline 5 mg/kg PO q12h.
• Tetracyclines 22 mg/kg PO q8h.
• Pradofloxacin 5 mg/kg PO q12h.
• Chloramphenicol 40–50 mg/kg IV, IM, 
SC, PO q8–12h.
• No standardized procedure for in vitro  
antimicrobial susceptibility tests.
• Topical antibiotic—conjunctivitis.
• Gentamicin.
• Kanamycin.
• Spectinomycin.
• Spiramycin.
• Tylosin.
• Erythromycin.
• Nitrofurans.
• Fluoroquinolones.
  FOLLOW‐UP
T reat for an extended period of time.PREVENTION/AVOIDANCE
• No vaccines are available.
• Organism readily killed by drying, 
sunshine, and chemical disinfection.
Prognosis good in animals with competent 
immune systems and given appropriate 
M. pneumoniae —infects respiratory tracts in 
humans worldwide; causes mycoplasmal 
pneumonia, bronchitis, or upper respiratory 
infection; usually self‐limited; rarely fatal.
• Not generally considered zoonotic unless 
person is immunosuppressed.
• Host specificity of mycoplasmas has been 
questioned by some, particularly between 
closely related species of mammals.
SYNONYMS
Pleuropneumonia‐like organisms.
• PCR‐DGGE = polymerase chain reaction 
denaturing gradient gel electrophoresis.
Lee‐Fowler T. Feline respiratory disease: what 
is the role of Mycoplasma species? J Feline 
Med Surg 2014, 16:563–571.
Reed N. Respiratory and ocular mycoplasmal 
infections: significance, diagnosis, and 
management. In: Little SE, ed., August’s 
Consultations in Feline Internal Medicine, 
7th ed. St. Louis, MO: Elsevier, 2016, pp. 
23–33.
Sykes JE. Mycoplasma infections. In: Sykes 
JE, ed., Canine and Feline Infectious 
Diseases. St. Louis, MO: Elsevier, 2014, pp. 
382–389.
available online(continued)  Mycoplasmosis

926  Blackwell’s Five-Minute Veterinary Consult  
MMycotoxicosis—Aflatoxin
  BASICS
OVERVIEW
Aflatoxins are hepatotoxic mycotoxins (mold 
toxins) and are the most commonly reported 
cause of mycotoxicosis associated with pet food. 
The four major forms of aflatoxin in feedstuffs 
are aflatoxin B1, B2, G1, and G2. Aflatoxin B1 
is the most common and most toxic.
• Rarely reported in dogs but occurs 
periodically in large outbreaks associated with 
pet foods.
• Reported experimentally in cats, rarely as 
field cases.
SIGNS
Acute Onset
• Most common presentation in small animals.
• Refusal of contaminated feeds.
• Rapid onset of signs may develop up to 
3 weeks post exposure.
• Vomiting and diarrhea.
• Icterus.
• Coagulopathy and gastrointestinal 
Chronic
• Anorexia or feed refusal.
• Ascites.
• Common in various cereal grains, peanuts, 
other nuts, and potatoes.
• Postproduction contamination of improp-
erly stored pet foods; foods with obvious 
mold spoilage; garbage ingestion.
• Mycotoxin-producing molds grow at 
temperatures of 24–35°C, moisture of 18–20%.
• Acute signs have been seen in dogs 
ingesting food containing 60 ppb aflatoxin.
• Activated to toxic epoxide by liver 
cytochrome P450 enzymes.
• Depletes glutathione.
• Binds with nucleic acids, proteins, and cell 
and organelle membranes.
  DIAGNOSIS
• Leptospirosis:
◦ Serology.
• Parvovirus:
◦ ELISA.
◦ Viral isolation.
• Anticoagulant rodenticide toxicosis:
◦ Anticoagulant rodenticide screen.• Other causes of subacute to chronic liver 
disease and associated disseminated intravas-
cular coagulation.
• Decreased serum protein C, antithrombin 
III, and cholesterol.
• Hyperbilirubinemia.
• Elevated alanine aminotransferase.
• Variable elevations in γ-glutamyltransferase, 
aspartate aminotransferase, and alkaline 
phosphatase.
Prolonged activated partial thromboplastin 
time (aPTT) and prothrombin time (PT).
• Liver biopsy.
• Histopathology.
• Assay suspect food samples for aflatoxin:
◦ Contaminated food is often gone due to 
delayed clinical signs.
• Hepatomegaly with fatty change.
• Icterus.
• Ascites.
• Multifocal hemorrhage, especially 
gastrointestinal.
• Microvesicular fatty change in 
hepatocytes.
• Centrilobular hepatocellular necrosis.
• Canalicular cholestasis.
• Bridging portal fibrosis, proliferation of 
bile ducts.
  TREATMENT
• T ransfusion of whole blood or plasma.
• Correct fluid and electrolyte imbalances.
• Activated charcoal for recent, high-dose 
exposure.
• B vitamins, vitamin K1, vitamin E, 
antioxidants, and hepatoprotectants.
• Gastroprotectants.
• Clean, uncontaminated diet:
◦ High-quality protein source.
• No specific antidotal therapy.
• Limited success with hepatoprotectants.
• Parenteral N-acetylcysteine in severely 
affected dogs—20% solution diluted 1:4 in 
sterile saline slow IV at a loading dose of 
140 mg/kg, follow with maintenance dose of 
70 mg/kg IV q8h × 7 doses.
• Oral S-adenosylmethionine—20 mg/kg PO 
daily as enteric-coated tablets given on empty 
stomach × 1–2 weeks.CONTRAINDICATIONS/POSSIBLE 
Avoid drugs metabolized by the liver.
  FOLLOW-UP
• Daily serum enzymes and chemistry, 
including cholesterol.
• PT and aPTT.
• Protein C.
• Consider as a cause of food refusal.
• Avoid using moldy feedstuff.
• Store food in cool, clean, dry area.
• Clean food containers and feed bowls 
regularly.
Chronic liver disease possible.
Prognosis—poor, even with treatment. 
Improved prognosis if treatment initiated 
before onset of signs.
Young animals more susceptible to aflatoxin.
• Indirect effects on uterus.
• Potentially teratogenic.
• Pregnant animals may be more susceptible.
• aPTT = activated partial thromboplastin time.
• PT = prothrombin time.
Arnot LF , Duncan NM, Coetzer H, et al. An 
outbreak of canine aflatoxicosis in Gauteng 
Province, South Africa. J S Afr Vet Assoc 
2012, 83(1):1–4.
Bischoff K, Garland T. Aflatoxicosis in dogs. In: 
Bonagura JD, T wedt DC, eds., Kirk’s Current 
Veterinary Therapy, 14th ed. St. Louis, MO: 
Saunders, 2009, pp. 156–159.
Bruchim Y, Segev G, Sela U, et al. Accidental 
fatal aflatoxicosis due to contaminated 
commercial diet in 50 dogs. Res Vet Sci 
2012, 93(1):279–287.
Author  Karyn Bischoff

Canine and Feline, Seventh Edition  927
MMycotoxicosis—Tremorgenic Toxins
  BASICS
OVERVIEW
• Penitrem A—produced by the fungus 
Penicillium crustosum  (and perhaps other 
Penicillium  spp.); poisoning by this toxin has 
been reported in dogs ingesting moldy bread, 
cheese, and English walnuts.
• Roquefortine—produced by Penicillium 
roquefortii  (and perhaps other Penicillium  
spp.); has been reported to cause poisoning in 
dogs through ingestion of moldy cheese or 
decaying organic material (compost).
• Poisoning by penitrem A and roquefortine 
has been reported in dogs of various ages and 
breeds soon after the ingestion of moldy 
foods or compost.
SIGNS
• Moderate to severe muscle tremors and 
seizures—begin minutes to hours (0.5–4 
hours in case reports) after ingestion of moldy 
food or compost.
• Affected dogs may be hyperresponsive to 
external stimuli.
• Early signs—may include panting, 
hyperactivity, vomiting, ataxia, incoordina-
tion, weakness, tachycardia, and/or rigidity.
• Prolonged muscle tremors or seizures—may 
lead to hyperthermia, hypoglycemia, 
dehydration, and anorexia.
• Severe cases—may result in death.
• Liver necrosis—has been reported 
experimentally.
• Dogs (and potentially cats) are exposed to 
penitrem A and roquefortine when they 
ingest moldy food or decomposing organic 
matter (compost).
• Experimentally, doses of 0.125 mg/kg 
penitrem A produced tremors within 30 
minutes. Doses of 0.5 mg/kg of penitrem A 
resulted in acute onset of tremors, severe liver 
necrosis, and death.
  DIAGNOSIS
• Toxic causes of seizures—strychnine; 
insecticides (e.g., organophosphate, carba-
mate, organochlorine, nicotine, pyrethroid); 
metaldehyde; zinc phosphide; bromethalin; 
methylxanthines (theobromine and caffeine); 
amphetamines; cocaine; sago palm; xylitol.
• Nontoxic causes of seizures—inflammation; 
congenital abnormal myelin formation; 
metabolic conditions (e.g., hepatic or uremic 
encephalopathy).CBC/BIOCHEMISTRY/URINALYSIS
CBC, biochemistry, and urinalysis to assess 
the patient’s status and to help rule out other 
causes of tremors and seizures.
N/A
IMAGING
N/A
• High-pressure liquid chromatography/mass 
spectroscopy—analysis of vomitus, stomach 
contents, and gastric lavage washings for 
penitrem A or roquefortine.
• The presence of roquefortine C in vomitus 
or stomach contents can serve as a sensitive 
biomarker for penitrem A intoxication.
• Bile analysis—reported to be of value.
• There are no pathognomonic lesions associated 
with penitrem A or roquefortine toxicosis.
• High doses of penitrem A have been reported 
to cause severe liver damage experimentally.
  TREATMENT
• Remove contaminated food or organic material.
• Induce vomiting (if patient is not at risk of 
aspirating vomitus) or institute gastric lavage 
followed by administration of activated charcoal.
• Control seizures.
• Thermoregulation as indicated.
• Diazepam 0.25–1 mg/kg IV PRN—to 
control tremors/seizures.
• Methocarbamol 50–220 mg/kg IV to 
control tremors/seizures; do not exceed 
330 mg/kg/day. Give 1/2 rapidly and 
administer rest to effect.
• Barbiturates phenobarbital 2–5 mg/kg IV 
PRN—if tremors and seizures cannot be 
controlled with diazepam.
• Sodium bicarbonate—may be required if 
an acid–base imbalance exists.
• Other symptomatic and supportive 
therapy—as indicated.
N/A
  FOLLOW-UP
Patients should be monitored for occurrence of 
tremors or seizures, hyperthermia, dehydration, acid–base imbalances, liver damage, rhabdomy -
olysis, and respiratory difficulties.
Prevent animals from eating moldy food 
items, garbage, or compost.
• Seizures—may not be controlled with 
diazepam.
• Acid–base imbalances—may develop.
• Hepatic damage and rhabdomyolysis—may 
occur.
• Aspiration pneumonia has been reported as 
a sequelae to vomiting and/or gastric lavage.
• Exposure can be fatal if lethal doses are 
consumed and are absorbed before 
gastrointestinal decontamination and therapy 
are instituted.
• Very good if appropriate therapy is 
promptly instituted, the toxin is removed 
from the gastrointestinal tract, and the 
seizures are controlled with diazepam, 
methocarbamol or barbiturates.
• Recovery in most clinical cases is reported 
to be complete within 24–48 hours.
• In a few reported cases, signs of weakness, 
muscle rigidity, and incoordination were 
persistent and slowly resolved over 1–2 weeks.
• A few severe cases have been reported to be 
fatal.
Barker AK, Stahl C, Ensley SM, et al. 
T remorgenic mycotoxicosis in dogs. 
35(2):E1–E6.
Puschner B. Mycotoxins. Vet Clin North Am 
Small Anim Pract 2002, 32:409–419.
Young KL, Villar D, Carson TL, et al. 
T remorgenic mycotoxin intoxication with 
penitrem A and roquefortine in two dogs. 
J Am Vet Med Assoc 2003, 222:52–53.
Author  Stephen B. Hooser

928  Blackwell’s Five-Minute Veterinary Consult  
MMyelodysplastic Syndromes
  BASICS
OVERVIEW
• Category of diseases characterized by 
nonregenerative anemias or cytopenias and 
dysplastic features in the blood or bone 
marrow.
• Primary myelodysplastic syndromes (MDS) 
result from a clonal expansion of a genetically 
altered pluripotent stem cell resulting in a 
hypercellular bone marrow with maturation 
arrest as a consequence of apoptosis.
• Subcategorized as MDS with excessive 
blasts, which may progress to acute myeloid 
leukemia, MDS with refractory cytopenia, 
and MDS with erythroid predominance.
• Secondary MDS in dogs is associated with 
neoplasia (lymphoma, multiple myeloma), 
drug or toxin exposure, immune-mediated 
disease, infections, or ionizing radiation 
exposure.
• Secondary MDS in cats is typically 
associated with feline leukemia virus (FeLV) 
• Dog and less commonly cat.
• Primary MDS typically older dogs.
SIGNS
• Fever.
• Petechiation.
• Heart murmur due to anemia.
• Viral—FeLV, feline immunodeficiency 
virus (FIV), parvovirus.
• Neoplasia—lymphoma, multiple myeloma.
• Autoimmune—immune-mediated 
hemolytic anemia, immune-mediated 
• Drugs—chemotherapeutics, estrogen, 
chloramphenicol, cephalosporins, phenylb-
utazone, trimethoprim-sulfadiazine, 
quinidine, thiacetarsamide, griseofulvin, 
• Iron deficiency, folic acid deficiency.
• Lead toxicity.
• Infectious—ehrlichiosis, bacterial 
septicemia, and endotoxemia.
  DIAGNOSIS
• Need to differentiate between primary and 
secondary MDS.• Other causes of nonregenerative anemias—
anemia of chronic disease, chronic renal 
failure, myeloproliferative diseases, 
lymphoproliferative diseases, myelofibrosis.
Nonregenerative anemia, cytopenias.
To diagnose underlying causes of secondary 
MDS—viral antigen/antibody titers, iron 
levels, tick titers, Coombs’ test.
IMAGING
• As needed to rule out secondary causes of 
MDS.
• Abdominal radiography—evaluate for lead 
foreign bodies.
• Abdominal ultrasonography—evaluate for 
abdominal masses consistent with retained 
testes and Sertoli cell tumors associated with 
estrogen secretion.
Bone marrow aspirate or biopsy.
  TREATMENT
• Inpatient or outpatient.
• If secondary MDS—treat underlying 
disease (e.g., discontinue drug, treat 
underlying infection).
• If neutropenic—limit exposure to other 
sick animals.
• Blood transfusions for anemic patients.
• For neutropenia—broad-spectrum 
antibiotics and filgrastim 3–5  μg/kg SC q24h 
• For anemia—erythropoietin 35–50 U/kg 
SC 3 times a week or darbepoetin 0.45  μg/kg 
once a week.
• Chemotherapy for primary MDS has been 
reported—hydroxyurea, cytosine arabinoside, 
prednisone, cyclosporine A, vincristine.
• Interferon α (cats with FeLV).
  FOLLOW-UP
• Serial monitoring of CBC for resolution of 
cytopenias.
• Prognosis dependent on primary vs. 
• Increasing blast percentage, multiple 
cytopenias, marked cellular atypia are poor 
prognostic factors for patients with primary 
MDS.  MISCELLANEOUS
• Do not use chemotherapy in pregnant or 
nursing animals.
• It is not recommended to breed animals 
with cancer.
SEE ALSO
• MDS = myelodysplastic syndromes.
Juopperi TA, Bienzle D, Bernreuter DC, et al. 
Prognostic markers for myeloid neoplasms: 
a comparative review of the literature and 
goals for future investigation. Vet Pathol 
2011, 48(1):182–197.

Canine and Feline, Seventh Edition  929
MMyelomalacia, Spinal Cord (Ascending, Descending, Progressive)
  BASICS
OVERVIEW
• Acute, progressive, ischemic and hemorrhagic 
necrosis of the spinal cord after acute spinal 
cord injury (SCI).
• First appears at the site of injury; then may 
progress cranially and caudally.
• Overall prevalence: 2% in dogs with acute 
thoracolumbar intervertebral disc herniation 
(IVDH), up to about 15% in more severely 
affected cases with paraplegia and loss of pain 
perception.
• Death usually caused by respiratory paralysis.
• Any age or breed.
• Because of the close association between 
acute (type I) IVDH and myelomalacia, 
chondrodystrophic breeds, particularly 
dachshunds, are more commonly affected 
because of their predisposition to the former.
• French bulldogs were at higher risk than 
dachshunds in one study.
SIGNS
• Not clinically recognizable in acute phase of 
SCI—suggestive clinical signs usually seen 
within 48 hours after presentation, but a 
delayed onset up to 2 weeks after injury has 
• Acute onset of paraplegia—initial clinical sign.
• Pain perception—usually absent caudal to 
the lesion (i.e., pelvic limbs and tail).
• Thoracolumbar injury—pelvic limbs 
paralysis with normal to exaggerated spinal 
reflexes in the pelvic limbs; some dogs might 
present with absent spinal reflexes (lesion at 
the lumbosacral intumescence or secondary to 
spinal shock).
• Involvement of the lumbosacral spinal cord 
segments within 12–72 hours, causing pelvic 
limb areflexia and atonia, loss of abdominal 
and anal tone and flaccid urinary bladder.
• Thoracic and cervical spinal cord segments 
may be involved within 24 hours to 10 days 
after initial injury, causing loss of cutaneous 
trunci muscle reflex, progression to tetraplegia, 
bilateral Horner syndrome, hypoventilation, 
and death.
• Extensive subarachnoid hemorrhage may 
cause hyperthermia and diffuse meningeal 
pain.
• Acute intervertebral disc herniation — 
herniation at the lumbosacral intumescence 
associated with higher risk.
• Acute, severe, spinal cord trauma.
• Fibrocartilaginous embolism or acute 
noncompressive nucleus pulposus extrusion.  DIAGNOSIS
• On presentation, cannot be differentiated 
from spinal shock (acute paralysis with initial 
areflexia improving after a few hours to days 
post injury) following acute SCI.
• Diagnosis based on hind limb upper motor 
neuron paralysis with absent nociception 
progressing to a lower motor neuron paralysis 
and rostrally advancing line of analgesia and 
cutaneous trunci reflex.
• Possible degenerative left‐shift caused by 
massive spinal cord necrosis.
Serum glial fibrillary acidic protein (GFAP)—
elevated; experimental only.
IMAGING
• Spinal survey radiographs—evidence of 
calcified, herniated disc, narrowed intervertebral 
disc space; vertebral fracture or luxation.
• Myelography—cord compression; edema; 
contrast medium infiltration into the spinal 
• MRI—extensive parenchymal T2 hyper­
intensity and spinal cord swelling; associated 
with other evidence of SCI.
CSF—unspecific results; hemorrhagic, 
neutrophilic pleocytosis and high protein 
Extensive, multifocal, necrosis of the spinal 
cord parenchyma with ischemic changes and 
multifocal hemorrhages.
  TREATMENT
• None to reverse spinal cord damage and 
stop disease progression.
• Rapid spinal cord decompression—
indicated for IVDH as delayed surgical 
treatment on dogs with complete sensori­
motor loss can alter chances of recovery; if 
performed less than 12 hours following loss of 
ambulation the risk of myelomalacia is 
decreased.
• Surgery does not always prevent its 
occurrence, especially if delayed: inform the 
owners of the risk of myelomalacia post­
operatively despite rapid intervention.
• Strong suspicion of myelomalacia—poor 
outcome, consider euthanasia.  MEDICATIONS
For palliative care—gabapentin 10 mg/kg PO 
q8h, opioids (fentanyl, hydromorphone) to 
relieve pain associated with SCI.
• Gabapentin may cause sedation.
• Opioids side effects include sedation, 
nausea, constipation, dysphoria.
  FOLLOW‐UP
In rare cases, condition progresses only 
caudally; paralysis is permanent, but 
respiratory compromise does not occur.
SEE ALSO
• GFAP = glial fibrillary acidic protein.
• SCI = spinal cord injury.
Balducci F , Canal S, Contiero B, et al. 
Prevalence and risk factors for presumptive 
ascending/descending myelomalacia in dogs 
after thoracolumbar intervertebral disk 
herniation. J Vet Intern Med 2017, 
31:498–504.
Castel A, Olby NJ, Mariani CL, et al. Clinical 
characteristics of dogs with progressive 
myelomalacia following acute intervertebral 
disc extrusion. J Vet Intern Med 2017, 
31:1782–1789.
Author  Aude M.H. Castel

M
930  Blackwell’s Five-Minute Veterinary Consult  
MMyelopathy—Paresis/Paralysis—Cats
  BASICS
• Myelopathy—any disease affecting the 
spinal cord; can cause paralysis (complete loss 
of voluntary movements) or paresis (weakness) 
that may affect all limbs (tetraparesis/plegia), 
the pelvic limbs (para-) only, the ipsilateral 
thoracic and pelvic limbs (hemi-), or one 
limb (mono-). • Paresis/paralysis can also be 
caused by neuromuscular disorders.
• Myelopathy—can affect gray or white 
matter of the spinal cord or, most often, both. 
• Lesions of the ascending white matter 
tracts—affect sensory modalities such as 
touch, pressure, proprioception, pain, and 
temperature sensation below the level of the 
lesion. • Lesions of the descending white 
matter tracts—affect the motor pathways 
producing signs of upper motor neuron 
disorder. The upper motor neuron cell bodies 
are located in the brain; they control voluntary 
activity and have inhibitory function on the 
lower motor neurons. Signs of upper motor 
neuron disease include paresis/paralysis, 
normal to increased muscle tone (hypertonia), 
and normal to exaggerated spinal reflexes 
(hyperreflexia) below the level of the lesion. 
• Lesions in the gray matter of the spinal 
cord—affect sensory and motor functions of 
the region innervated by the nerves whose cell 
bodies are located in the gray matter. The 
motor nerves in the gray matter of the spinal 
cord are also called lower motor neurons. 
Signs of lower motor neuron disease include 
paresis/paralysis, decreased or absent muscle 
tone (hypo- or atonia), atrophy of the muscles 
innervated by that segment, and reduced or 
absent spinal reflexes (hypo- or areflexia).
GENETICS
• Lysosomal storage diseases—gangliosidosis 
GM1/GM2, sphingomyelinosis (Niemann–
Pick disease), mucopolysaccharidosis VI 
(MPS VI), and glycogenosis type IV cause 
paresis or paralysis in cats; autosomal recessive 
pattern of inheritance. • Neuroaxonal 
dystrophy and spinal muscular atrophy—
degenerative diseases of the spinal cord 
reported as autosomal recessive conditions. 
• Syringohydromyelia/myelodysplasia may be 
associated with sacrocaudal (sacrocoggygeal) 
dysgenesis—autosomal dominant condition 
in Manx cats.
• Gangliosidosis GM1/GM2—Siamese, 
Burmese, Korat cats, and domestic 
shorthair (DSH). • Glycogen storage 
disease type IV—Norwegian forest cats. • Spinal muscular atrophy—Maine coon. 
• Syringohydromyelia/myelodysplasia—
Manx and Manx crosses with sacrocaudal 
dysgenesis. • Sphyngomyelinosis (Niemann–  
Pick disease)—Siamese, Balinese, and 
DSH. • Mucopolysaccharidosis type VI—  
Siamese and DSH. • Mucopolysaccharidosis 
type VII—DSH. • Idiopathic complex 
polysaccharide storage disease—Abyssinians. 
• Neuroaxonal dystrophy—Siamese and DSH.
SIGNS
• Signs vary with location and severity of 
lesion. • Cervical lesion (spinal cord segments 
C1–5)—all limbs or ipsilateral limbs affected 
with proprioceptive ataxia and tetraparesis/
plegia, hemiparesis/plegia; normal to 
increased reflexes and tone; ± neck pain; ± 
ipsi-/bilateral Horner’s syndrome; ± urinary 
incontinence with bladder difficult to express; 
increased urethral sphincter tone and tense 
bladder. • Cervicothoracic lesion (C6–T2)—
all limbs or ipsilateral limbs affected with 
proprioceptive ataxia and tetraparesis/plegia, 
hemiparesis/plegia; hypo-/areflexia, hypo-/
atonia and muscle atrophy in thoracic limbs 
with normal to increased reflexes and tone in 
pelvic limbs; ± neck pain; ± ipsi-/bilateral 
Horner’s syndrome; ipsi-/bilateral decreased/
absent cutaneous trunci reflex; ± urinary 
bladder. • Thoracolumbar lesion (T3–L3)—
normal thoracic limbs; both pelvic limbs or 
ipsilateral pelvic limb affected with 
proprioceptive ataxia and paraparesis/plegia; 
normal to increased reflexes and tone; ± 
thoracolumbar pain; ± decreased/absent 
cutaneous trunci reflex below the lesion; ± 
decreased/absent sensation below lesion; ± 
Schiff–Sherrington posture; ± urinary 
incontinence with bladder difficult to express, 
bladder. • Lumbosacral lesion (L4–S3) —
ipsilateral limb affected with proprioceptive 
ataxia and paraparesis/plegia or monoparesis/
plegia; hypo-/areflexia; hypo-/atonia; muscle 
atrophy; ± regional pain; ± urinary and fecal 
incontinence, large and flaccid bladder easy to 
express, decreased urethral sphincter tone; ± 
decreased or absent tail and anal tone; ± 
decreased or absent sensation below lesion.
CAUSES
• Degenerative and/or inherited—
neuroaxonal or neuronal dystrophy, spinal 
muscular atrophy, storage diseases 
(gangliosidosis GM1/GM2, sphingo -
myelinosis, glycogenosis type IV, idiopathic 
complex polysaccharide storage disease, and 
mucopolysaccharidosis type VI) and spinal 
dural ossification. • Anomalous—
syringohydromyelia, myelodysplasia, 
meningocele or meningomyelocele, and tethered spinal cord often associated with 
sacrocaudal dysgenesis, spinal arachnoid cyst, 
spinal intradural epithelial cyst, spinal 
dermoid cyst/sinus. • Metabolic—
hypervitaminosis A, nutritional secondary 
hyperparathyroidism, cobalamine deficiency-
associated myelopathy. • Neoplastic—
lymphoma, vertebral column neoplasia 
(osteosarcoma, fibrosarcoma, plasma cell 
tumor, and chondrosarcoma), meningiomas, 
sarcomas, histiocytic tumors, glial tumors 
(astrocytoma, oligodendroglioma, gliomatosis 
cerebri), primitive neuroectodermal tumors, 
peripheral nerve sheath tumors, and 
metastatic tumors. • Inflammatory or 
infectious—feline infectious peritonitis (FIP), 
Borna virus (Europe), bacterial meningo -
myelitis, fungal meningomyelitis ( Cryptococcus 
neoformans , Coccidioides immitis , Histoplasma 
capsulatum ), Toxoplasma gondii  meningomyelitis, 
eosinophilic meningomyelitis, idiopathic 
poliomyelitis, and feline leukemia virus 
(FeLV)-associated myelopathy. • T raumatic—
vertebral fractures/luxations and penetrating 
wounds (bite wounds, BB pellets, microchips); 
intervertebral disc disease. • Vascular—
ischemia or infarct of unknown etiology, 
fibrocartilaginous embolisms, ischemic 
myelopathy secondary to hyaline arteriopathy, 
intraosseous vascular malformations, and 
myelopathy secondary to aortocaval fistula.
• Outdoor cats—at risk for traumatic and 
infectious myelitis.
• FeLV-positive cats—at risk for lymphoma 
and FeLV-associated myelopathy.
  DIAGNOSIS
Differentiate from other disease processes that 
can cause paresis/paralysis—ischemic neuro -
myopathy caused by arterial thromboembo -
lism, and peripheral neuromuscular diseases 
such as diabetic neuropathy, polyradiculoneuritis, 
hypokalemic myopathy, muscular dystrophy, 
polymyositis, and myasthenia gravis.
• Often normal. • Various nonspecific 
abnormalities can be found associated with 
infectious myelitis and lymphoma. 
• Lysosomal storage diseases—abnormal 
accumulation of products of cell metabolism 
can be seen within the cytoplasm of 
peripheral leukocytes.
• Serology—FeLV/FIV, Cryptococcus 
neoformans, Coccidioides immitis, 
Histoplasma capsulatum, and Toxoplasma 
gondii. • Latex agglutination test—

Canine and Feline, Seventh Edition  931
MMCryptococcus neoformans (serum or CSF). 
• α-Acid glycoprotein (AGP) can be used as a 
discriminating marker for FIP when coupled 
with other high-risk factors. • Urine metabolic 
screening for lysosomal storage diseases. 
• Genetic tests for inherited myelopathies—
see a frequently updated list of tests available 
worldwide and genetic testing laboratories in 
IMAGING
• Spinal radiography—may reveal congenital 
or acquired (MPS VI) vertebral malformations, 
discospondylitis, vertebral fractures and 
luxations, bony tumors, and radiographic 
signs suggestive of intervertebral disc disease. 
• Myelography—may reveal extradural 
compression consistent with intervertebral 
disc disease or tumor, or intradural–
extramedullary tumors. • CT—more 
sensitive than radiography for diagnosis of 
discospondylitis, vertebral fractures, and bony 
tumors; may reveal syringomyelia and 
intramedullary tumors. • MRI—more 
sensitive than CT for diagnosis of intra -
medullary tumors, inflammatory/infectious 
and vascular diseases, and anomalies, such as 
syringomyelia, myelodysplasia, meningocele 
or meningomyelocele, tethered spinal cord, 
spinal arachnoid cyst, spinal intradural 
epithelial cyst, and spinal dermoid cyst/sinus.
• To confirm an inflammatory process 
affecting meninges and/or spinal cord. 
• Elevated total nucleated cell count and 
proteins suggest an inflammatory process 
affecting meninges and/or spinal cord; should 
be examined for fungal and bacterial 
organisms. • Other laboratory tests 
performed on CSF—latex agglutination test 
for Cryptococcus neoformans ; ELISA for 
Cryptococcus neoformans  and Histoplasma 
capsulatum ; PCR for feline coronavirus and 
Toxoplasma gondii ; bacterial and fungal 
culture.
Electromyography, nerve conduction velocity, 
repetitive stimulations—help differentiating 
paresis/paralysis caused by a myelopathy from 
peripheral neuromuscular disorders.
  TREATMENT
• Emergency evaluation and possible surgery—  
when a traumatic cause of paresis/paralysis is 
suspected. • Inpatient medical management—
for severe neurologic deficits such as paralysis 
and urinary incontinence.NURSING CARE
• Non-ambulatory cats should be confined to 
a soft padded crate or enclosed area, kept dry 
and clean, and turned every 6 hours if they 
are not able to assume a sternal position. • If 
there is urinary incontinence, the bladder 
should be expressed every 8 hours. • Prevent/
treat decubital ulcers and urine scalding. 
• T reat constipation. • Physical therapy is 
useful to prevent muscle atrophy and 
contractures and to keep the joints flexible, 
especially for postoperative rehabilitation in 
vertebral trauma or intervertebral disc disease.
If the cat is treated as an outpatient, discuss 
all aspects of nursing care and possible 
complications with the client.
Surgical management—for vertebral fractures 
and luxations, intervertebral disc disease, and 
some neoplasms. The objectives of surgical 
management should be decompression of the 
spinal cord, and/or reduction and stabilization 
of the fracture/luxation.
• Not recommended until a diagnosis has 
been established. • Spinal trauma—
controversial: in experimental studies of acute 
spinal cord injury (ASCI) in cats, the 
administration of methylprednisolone sodium 
succinate (MPSS) within 8 hours from injury 
(30 mg/kg initial bolus, followed by MPSS 
CRI of 5.4 mg/kg/h for 24 hours or 15 mg/
kg q6h for 2 doses) led to improved 
neurologic function; however, these studies 
have not been replicated in a clinical setting. 
Please note that the use of high-dose 
glucocorticoids in trauma patients has been 
associated with hyperglycemia, pneumonia, 
urinary tract infection, gastrointestinal 
ulceration, and increased mortality. 
Dexamethasone was not found to improve 
neurologic outcome in experimental cat 
models of ASCI.
Glucocorticoids—contraindicated when an 
infectious disease is suspected; may also alter 
CSF , MRI, or CT results, precluding reaching 
a diagnosis.
  FOLLOW-UP
• Urinary infection. • Urine scalding. 
• Constipation or fecal incontinence. • Muscle atrophy and contractures. 
• Decubital ulcers.
• Cats <2 years—myelopathies often caused 
by anomalous or inherited, inflammatory, or 
infectious, metabolic, and traumatic diseases. 
FIP is the most important cause of myelopathy 
in this age group. • Cats 2–8 years—
lymphoma (LSA), FIP , and trauma are 
important causes of myelopathy. • Cats >8 
years—vascular and neoplastic diseases more 
common, especially LSA and vertebral tumors.
Toxoplasma gondii  infections represent a 
zoonotic potential.
SEE ALSO
Schiff–Sherrington Phenomenon.
• AGP = α-Acid glycoprotein.
• DSH = domestic shorthair.
• MPS = mucopolysaccharidosis.
PennGen DNA Tests Available Worldwide for 
Canine and Feline Hereditary Diseases: 
https://www.vet.upenn.edu/research/
penngen/tests-worldwide
Aharon MA, Prittie JE, Buriko KA. review of 
associated controversies surrounding 
glucocorticoid use in veterinary emergency 
and critical care. J Vet Emerg Crit Care 
2017, 27:267–77.
Marioni-Henry K, Van Winkle TJ, Smith 
SH, et al. T umors affecting the spinal cord 
of cats: 85 cases (1980–2005). J Am Vet 
Med Assoc 2008, 232:237–243.
Marioni-Henry K, Vite CH, Newton AL, 
et al. Prevalence of diseases of the spinal 
cord of cats. J Vet Intern Med 2004, 
8:851–858.
Sharp B. Feline physiotherapy and 
 rehabilitation: 2. clinical applications. 
J Feline Med Surg 2012, 14:633–645.
Author  Katia Marioni-Henry 
available online(continued)  Myelopathy—Paresis/Paralysis—Cats

932  Blackwell’s Five-Minute Veterinary Consult  
MMyeloproliferative Disorders
  BASICS
OVERVIEW
• Unregulated neoplastic proliferation of 
nonlymphoid cells originating in the bone 
marrow (granulocytic, monocytic, erythrocytic, 
and megakaryocytic cells) resulting in accumu-  
lations of differentiated cells.
• Includes polycythemia vera, chronic 
myelogenous leukemia, essential thrombo-
cythemia, and possibly primary myelofibrosis.
• Believed to represent a spectrum of 
disorders in which the stem cell involved is a 
hematopoietic precursor capable of differenti-
ating into all blood cell types except 
• Cats and dogs—more common in cats.
• May be more common in large-breed dogs 
than small-breed dogs.
SIGNS
• Inappetance.
• Peripheral lymphadenomegaly— 
occasionally.
• Neurologic signs—disorientation, ataxia, 
seizure.
• Cats—most commonly associated with 
feline leukemia virus (FeLV) infection; when 
recovering from panleukopenia or hemo -
bartonellosis, may be a relatively higher risk 
of developing a mutant cell line induced by 
FeLV.
• Dogs—has been experimentally induced 
with chronic low-dose radiation exposure.
  DIAGNOSIS
• Acute lymphocytic leukemia—usually 
differentiated by special staining techniques 
(immunohistochemistry or immuno -
cytochemistry for lymphoid markers) or PCR 
for antigen receptor rearrangement (PARR).
• Leukemoid response secondary to 
• Other causes of eosinophilia—parasitism; 
allergic disease; eosinophilic gastroenteritis; 
mast cell neoplasia; differentiate from 
eosinophilic leukemia.
• Relative and secondary absolute polycythemia.
• Reactive thrombocytosis—secondary to 
inflammation, hemolytic or iron-deficiency 
anemia, splenectomy, rebound from immune- mediated thrombocytopenia, and drug-
induced (e.g., vincristine).
• Severe, nonregenerative anemia.
• Severe elevated hematocrit in cases of 
primary polycythemia vera.
• Circulating nucleated red blood cells.
• Megaloblastic erythrocytes.
• Leukocytosis or leukopenia.
• Thrombocytopenia with abnormal platelet 
morphology.
• Thrombocytosis in cases of essential 
thrombocythemia.
• Circulation of immature myeloid cells.
• Examination of bone marrow aspirate or 
core biopsy—reveals hypercellular bone 
marrow with abnormal morphology in all cell 
lines; neoplastic proliferation or absence of 
one cell line.
• Immunohistochemical or other special 
stains—may be necessary to determine cell 
lineage.
IMAGING
Abdominal radiography and ultrasonogra-
phy—hepatomegaly and splenomegaly 
common.
Examination of bone marrow aspirates or 
core biopsy.
  TREATMENT
• Outpatient or inpatient.
• Supportive care—blood transfusions and 
fluid administration to correct dehydration.
• Therapeutic phlebotomies.
• Radiophosphorus (32P) has been effective in 
cases of polycythemia vera and essential 
thrombocythemia but there are limited 
facilities that can offer this therapy.
• Seek consultation from a veterinary 
oncologist regarding treatment.
• Little information available in the literature 
regarding treatment.
• Cytosine arabinoside—may be used; 
100 mg/m2 SC divided q12h 4 days per week, 
or as a constant rate infusion over 6–8 hours 
at a dose of 400 mg/m2.
• Hydroxyurea 30–45 mg/kg q24h for 7–10 
days; then 30–45 mg/kg q48h or 15 mg/kg 
q24h; initially, titrate dosage to patient 
response.
• Antibiotics—may be indicated to combat 
secondary infection.CONTRAINDICATIONS/POSSIBLE 
Chemotherapy can be toxic; seek advice 
before treatment if unfamiliar with cytotoxic 
drugs.
  FOLLOW-UP
• Complete blood count and examination of 
bone marrow aspirate—determine response 
to treatment and progression of disease.
• Prognosis—guarded.
• Chemotherapy drugs are contraindicated in 
with neoplasia.
• PARR = polymerase chain reaction for 
antigen receptor rearrangement.
Young KM, Vail DM. Canine acute myeloid 
leukemia, myeloproliferative neoplasms, 
and myelodysplasia. In: Withrow SJ, Vail 
DM, Page RL, eds., Small Animal Clinical 
Oncology, 5th ed. Philadelphia, PA: 
Saunders, 2013, pp. 653–665.

Canine and Feline, Seventh Edition  933
MMyocardial Infarction
  BASICS
OVERVIEW
• Rapid development of myocardial necrosis 
resulting from sustained, complete reduction 
of blood flow to a portion of the myocardium, 
caused by thrombus formation. 
• Uncommon as a naturally occurring disease 
in dogs. • Microscopic intramural myocardial 
infarctions and focal areas of myocardial 
fibrosis are common in dogs with acquired 
cardiovascular disease. • Consistent electro­
cardiogram (ECG) characteristics of 
spontaneous myocardial infarction are not 
well characterized in dogs and cats.
Rare in dog and cat
SIGNS
• Lethargy. • Anorexia. • Weakness. 
• Dyspnea. • Collapse. • Vomiting. 
• Obesity. • Unexpected death.
• Lameness. • Tachycardia. • Heart murmur. 
• Cardiac rhythm disturbances. • Low‐grade 
fever.
Dogs
• Atherosclerosis and coronary artery disease. 
• Nephrotic syndrome. • Vasculitis. 
• Hypothyroidism. • Bacterial endocarditis. 
• Neoplasia. • Septicemia. • Intramural 
coronary arteriosclerosis in old dogs. 
• Subvalvular aortic stenosis.
Cats
• Cardiomyopathy. • Thromboembolism.
  DIAGNOSIS
Generally presumptive, based on acute onset of 
signs in a patient with predisposing factors, consistent ECG changes (ST segment changes) 
and elevated circulating biomarkers (cardiac 
troponin I [cTnI]).
Other Causes of ST Segment Changes
• Normal variation. • Myocardial ischemia/
hypoxia. • Hyperkalemia or hypokalemia. 
• Digitalis toxicity. • T rauma to the heart. 
• Pericarditis. • Artifact—wandering baseline.
Other Causes of Weakness and Collapse
• T rauma. • Neurologic disease. 
• Thromboembolism. • Pericardial effusion. 
• Arrhythmia.
• Mild leukocytosis. • High liver enzymes. 
• Hyperlipidemia—if animal is hypothyroid. 
• High amylase. • High creatine kinase and 
cardiac isoenzymes. • High cTnI.
Low triiodothyronine (T3) and thyroxine (T4).
IMAGING
Echocardiography—2D and M‐mode 
echocardiography useful in evaluating wall 
motion abnormalities and overall left 
ventricular function.
Electrocardiographic Findings
• Sudden deviation of the ST segment 
(Figure 1). • Tall peaked T waves—first few 
hours. • Sudden development of Q waves or 
a change in direction of the T wave. • Axis 
shift of the frontal plane. • Low‐voltage QRS 
complexes. • Sudden development of bundle 
branch block or heart block. • Sudden onset 
of ventricular arrhythmias because of 
myocardial ischemia. • Sloppy “R” wave 
descent may be associated with intramural 
myocardial infarction.
  TREATMENT
• T reat the underlying disorder; likewise the 
symptomatic therapy (e.g., congestive heart failure [CHF]). • Must identify and 
immediately treat life‐threatening arrhythmias.
• IV thrombolytic agents—(e.g., 
streptokinase); cost prohibitive and lack of 
experience with myocardial infarction in 
veterinary medicine with dosage and use. 
• Lidocaine for ventricular arrhythmias. 
• Beta‐blockers—use cautiously with dilated 
cardiomyopathy because of possible 
development of low‐output CHF . 
• Antithrombotic agents (e.g., dalteparin; low 
molecular weight heparin, heparin and aspirin).
  FOLLOW‐UP
• Determined by clinical status and diagnosis 
of underlying disorder. • Monitor anticoagulated 
patient; CBC and bleeding profiles, including 
fibrinogen.
• CHF = congestive heart failure. • cTnI = 
cardiac troponin I. • ECG = electrocardiogram. 
• T3 = triiodothyronine. • T4 = thyroxine.
Driehuys E, Van Winkle TJ, Sammarco CD, 
Drobatz KJ. Myocardial infarction in dogs 
and cats: 37 cases (1985–1994). J Am Vet 
Med Assoc 1998, 213:1444–1448.
Kidd L, Stepien RL, Amoheim DP . Clinical 
findings and coronary artery disease in dogs 
and cats with acute & subacute myocardial 
necrosis: 28 cases. J Am Anim Hosp Assoc 
2000, 36:199–208.
Figure 1 .
T ransmural infarction of the left ventricle in a dog with arteriosclerosis and hypothyroidism. The first three rapid successive complexes represent ventricular tachycardia. 
The sinus rhythm that follows illustrates small complexes, marked elevation of the ST segment, and first‐degree atrioventricular block (prolonged PR interval). (Source: 
From Tilley LP . Essentials of Canine and Feline Electrocardiography, 3rd ed. Baltimore: Williams & Wilkins, 1992. Reprinted with permission of Wolters Kluwer.)

934  Blackwell’s Five-Minute Veterinary Consult  
MMyocardial Tumors
  BASICS
OVERVIEW
• Primary and metastatic myocardial tumors 
are rare tumors in dogs and cats; incidence 
0.19% in dogs and 0.03% in cats.
• Reported primary tumors include 
hemangiosarcoma, ectopic thyroid carcinoma, 
lymphoma, with less frequently documented 
rhabdomyoma, rhabdomyosarcoma, 
thymoma, mesothelioma, chondrosarcoma, 
osteosarcoma, fibrosarcoma, myxoma, 
myxosarcoma, lipoma, peripheral nerve 
sheath tumor, and granular cell tumor.
• Dogs and cats—but less common in cats.
• In dogs—any age but more common 
between 7 and 15 years.
• Possible increased incidence in neutered 
animals.
• Increased incidence in Saluki, French 
bulldog, Irish water spaniel, flat-coated 
retriever, golden retriever, boxer, Afghan 
hound, English Setter, Scottish terrier, Boston 
terrier, bulldog, German shepherd dog.
SIGNS
• Sudden collapse.
• Dyspnea.
• Acute death.
Unknown
  DIAGNOSIS
• Valvular disease.
• Heart base tumors.
Anemia in some patients.
Serum/plasma cardiac troponin I levels are 
increased in patients with cardiac hemangio-
sarcoma and might have utility for the 
detection of other myocardial neoplasms.
IMAGING
• Thoracic radiography—may reveal a 
globoid heart suggestive of pericardial effusion, masses in the area of the atria, or 
metastatic lesions in the lungs.
• Echocardiography—helpful in finding 
primary masses; positive predictive value of 
92%, negative predictive values 64%.
• Advanced imaging such as CT, positron 
emission tomography (PET) scan, and MRI 
may be helpful in defining mass lesions.
• Pericardiocentesis and fluid evaluation—
helpful in diagnosis of lymphoma.
• Cytology of pericardial effusion limited in 
usefulness in differentiating neoplastic from 
non-neoplastic effusions.
• ECG—may be normal or display a variety 
of arrhythmias; may see electrical alternans 
and small complexes with pericardial effusion.
• Surgical biopsy of mass—if possible.
  TREATMENT
• Pericardectomy—may offer relief of 
pericardial effusion.
• Address concern for sudden death with owner.
• Management of arrhythmias—lidocaine 
(dogs) 2–4 mg/kg IV (to a maximum 8 mg/
kg over 10-minute period), CRI—25–75 μg/
kg/minute IV, mexiletine (dogs) 5–8 mg/kg 
PO q8–12h, sotalol 1–2 mg/kg PO q12h.
• Chemotherapy dependent on tumor type 
(see Lymphoma—Cats, Lymphoma—Dogs, 
and Hemangiosarcoma, Heart).
  FOLLOW-UP
• Serial echocardiograms—to monitor tumor 
response to chemotherapy.
ultrasonography—to monitor for metastatic 
• ECG—to monitor response to antiar-
rhythmogenic medications.
• Prognosis—guarded to poor.  MISCELLANEOUS
• Chemotherapy is teratogenic—do not give 
to pregnant animals.
SEE ALSO
• Chemodectoma.
• Hemangiosarcoma, Heart.
• PET = positron emission tomography.
T reggiari E, Pedro B, Dukes-McEwan J, et al. 
A descriptive review of cardiac tumours in 
dogs and cats. Vet Comp Oncol 2017, 
15(2):273–288.

Canine and Feline, Seventh Edition  935
MMyocarditis
  BASICS
• Inflammation of the myocardium, definitive 
identification of which requires histologic 
examination. • In humans, the widely accepted 
Dallas criteria specify that necrosis and/or 
degeneration of myocytes adjacent to 
inflammatory infiltrates is a requisite for 
diagnosis. • Causes are diverse and include 
infective (viral, bacterial, protozoal, mycotic) 
pathogens and noninfective (toxic, possibly 
immune) disease agents. • T raumatic 
myocarditis is a term applied to the syndrome 
of arrhythmias that sometimes complicates 
blunt trauma. The term is a misnomer because 
myocardial lesions (if present) are more likely to 
take the form of necrosis than inflammation.
• Numerous mechanisms, determined partly 
by the nature of the causative agent, are 
implicated. • Microbial agents and toxins can 
result in direct cellular damage causing cell 
death, activation of the immune system, and 
inflammation. • Though incompletely 
described in veterinary patients, chronic 
myocarditis, immune myocarditis and 
autoreactive myocarditis—the latter occurring 
in the absence of microbial agents—as well as 
dilated cardiomyopathy (DCM) are potential 
sequelae of acute myocarditis. • The cellular 
character of inflammation is partly determined 
by the nature of the pathologic insult; 
protozoal and mycotic agents result in 
pyogranulomatous infiltrates, while viral 
myocarditis is generally lymphocytic. 
• Myocardial involvement may be focal or 
diffuse. • Canine parvoviral infection can 
result in myocarditis in pups, and has been 
implicated as a cause of DCM. The virus has 
tropism for dividing cells, and adult myocytes 
do not replicate. Parvovirus myocarditis is 
most likely to occur in unvaccinated pups 
from immunologically naïve dams. 
• Protozoal myocarditis resulting from 
Trypanosoma cruzi  infection causes Chagas 
disease. Acute phase illness is characterized 
primarily by electrocardiogram (ECG) 
abnormalities. Chronic infection can result in 
myocardial dysfunction and development of 
heart failure. • It has been hypothesized that 
feline endomyocarditis might be a precursor 
of restrictive cardiomyopathy; recent findings 
implicate infection by Bartonella  spp. 
• Bacterial myocarditis can be observed in 
patients with overwhelming sepsis. 
• Bacterial, protozoal, and mycotic 
myocarditis may reflect immunosuppression. 
• An apparently rare, as yet idiopathic, atrial 
myocarditis might be important in the 
pathogenesis of persistent canine atrial 
standstill. • The pathogenetic importance of 
myocardial inflammation in canine arrhythmogenic right ventricular cardio­
myopathy is unresolved; however, myocarditis 
is observed in a substantial proportion of 
cases. • The pathogenesis of traumatic 
myocarditis is incompletely defined; direct 
trauma resulting in necrosis is likely 
responsible in some cases, but extracardiac 
factors including electrolyte derangements, 
hypoxia, acid–base disturbances, and altered 
function of the autonomic nervous system 
might contribute.
• Systemic involvement depends on the 
causative agent. • Cardiovascular—
myocardial dysfunction and/or arrhythmias. 
• Respiratory—if pulmonary edema develops.
• Histologically confirmed myocarditis is 
rarely identified in veterinary patients, 
therefore epidemiology of myocarditis is 
incompletely described. • Viral myocarditis is 
seemingly rare. • Chagas disease is 
uncommon and occurs primarily in the 
southern United States. • Fungal myocarditis—  
primarily seen in association with systemic 
fungal infection—is rare and occurs 
regionally, where mycoses are endemic. 
• Spirochetal myocarditis and atrioventricular 
(AV) block resulting from Borrelia burgdorferi  
infection has been reported, but seemingly is 
rare. • Infection by Bartonella  spp. has been 
associated with canine and feline myocarditis.
Myocarditis can result from infectious agents 
that have distinct geographic distributions.
Species
Largely unknown.
SIGNS
• Related to the extent and duration of 
myocardial involvement. • Signs relating to 
arrhythmias or heart failure are most common. 
• Onset of cardiac dysfunction in association 
with systemic illness should prompt consider­
ation of myocarditis and, because myocardial 
disease in veterinary patients is often familial, 
development of cardiac dysfunction in patients 
with atypical signalment suggests the possibility 
of myocarditis.
• Coughing, exercise intolerance, dyspnea—
associated with congestive heart failure (CHF).  
• Syncope and weakness—associated with 
arrhythmias. • Concurrent manifestations of 
systemic disease reflective of the etiologic 
agent. • Road traffic or other accidents often 
precede the development of traumatic 
myocarditis.Physical Examination Findings
• Gallop sounds or murmurs may be heard. 
• Arrhythmias—may be auscultated. 
• Fever—potentially observed in patients 
with infective myocarditis. • Evidence of 
injury in those with traumatic myocarditis.
CAUSES
• Virus (e.g., parvovirus, distemper virus, 
herpesvirus, West Nile virus). • Protozoa 
(e.g., T. cruzi , Toxoplasma gondii , Neospora 
caninum , Hepatozoon canis , Babesia  spp., and 
Leishmania  spp.). • Bacteria (e.g., Bartonella 
vinsonii  subsp . berkhoffii ). • Fungi (e.g., 
Cryptococcus neoformans, Coccidioides immitis, 
Blastomyces dermatitidis,  and Aspergillus 
terreus ). • Algae (e.g., Prototheca  spp.). 
• Blunt trauma can result in the syndrome of 
traumatic myocarditis.
• Exposure to infectious agents. 
• Immunosuppression. • Debilitating 
diseases. • T rauma.
  DIAGNOSIS
• Consider the possibility that preexisting 
heart disease such as congenital defects, 
cardiomyopathy, and acquired valvular disease 
are responsible for clinical findings. • History 
of a heart murmur or the presence of 
arrhythmias before onset of systemic illness 
helps differentiate from other diseases. 
• Extracardiac organ involvement and 
identification of infectious agents may aid in 
the diagnosis. • History of road traffic 
accident generally makes the diagnosis of 
traumatic myocarditis obvious.
Abnormalities—vary, depending on organ 
• Serologic tests can be used to detect 
exposure to infectious agents. • Cytologic 
examination of pericardial, pleural, and 
peritoneal effusions to identify the infectious 
organism. • Blood culture to identify 
bacteremia. • T roponin—concentrations 
might be high and reflect myocyte necrosis.
IMAGING
• Cardiac silhouette may be enlarged if 
myocarditis has resulted in cardiac 
dysfunction; potential consequences of 
cardiac dysfunction include: pulmonary 
edema and/or pleural effusion. • Pulmonary 
granuloma may be found in animals with 
granulomatous myocardial infection. 
• Evidence of trauma potentially including 
pulmonary contusions or pneumothorax.

936  Blackwell’s Five-Minute Veterinary Consult  
MEchocardiography
• Reflects the extent of myocardial damage; 
may be normal if lesions are small or 
primarily affect the conduction system. 
• Evaluation of systolic myocardial function 
might reveal minor segmental abnormalities, 
or global dysfunction associated with 
chamber enlargement. • In humans and 
experimental models, an increase in wall 
thickness has been associated with 
inflammatory infiltrates/edema; this 
observation might be relevant to the 
syndrome of “transient wall thickening” 
observed in cats. • Pericardial effusion in 
patients with pancarditis. • In exceptional 
cases granulomas result in echocardiographically 
evident masses.
ECG
• Arrhythmias of all types—supraventricular 
tachyarrhythmias, ventricular tachy­
arrhythmias, and bradyarrhythmias, perhaps 
particularly AV block—can be observed in 
association with inflammatory myocardial 
disease. • Arrhythmias associated with 
trauma—ventricular tachyarrhythmias occur 
in most affected patients; supraventricular 
arrhythmias and bradyarrhythmias are rare. 
Ventricular rhythms that complicate blunt 
trauma often have relatively slow rates 
detected only during pauses in the sinus 
rhythm; they are most appropriately referred 
to as accelerated idioventricular rhythms 
(AIVRs). The QRS complexes are wide and 
bizarre; the rate is >100 bpm but <160 bpm. 
Usually, these rhythms are electrically and 
hemodynamically benign. However, 
dangerous ventricular tachycardias can 
complicate blunt trauma and evolve from 
seemingly benign AIVRs, compromising 
perfusion and placing the patient at risk for 
Endomyocardial Biopsy
A minimally invasive technique that is 
required for definitive ante ­mortem diagnosis 
but rarely performed in veterinary patients.
Pericardiocentesis
• Alleviates tamponade caused by pericardial 
effusion. • Submit fluid for cytologic exam  ­ 
ination and, possibly, bacterial culture.
Holter Monitoring
• To define the burden of arrhythmia in 
terms of frequency and character over a 24 ­48 
hour period. • To monitor antiarrhythmic 
therapy.
• Dilated cardiac chambers with patchy areas 
of hyperemia, necrosis, or fibrosis. 
• Granulomas seen grossly in some patients. 
• Histologic examination of the myocardium 
or pericardium may reveal inflammatory cells 
(e.g., lymphocytes, plasma cells, and 
macrophages), patchy fibrosis, or the 
infectious agents themselves.  TREATMENT
• Hospitalize patients with decompensated 
heart failure for initial medical management. 
• Hospitalize patients with hemodynamically 
consequential ventricular arrhythmias for 
initial, parenteral antiarrhythmic therapy. 
• Hospitalize patients with severe systemic 
manifestations for appropriate medical therapy.
ACTIVITY
DIET
Sodium restriction if CHF .
• Cardiac manifestations may persist even 
after resolution of systemic illness. • Certain 
arrhythmias (e.g., ventricular tachycardia, 
third ­degree AV block) may predispose to 
sudden death. • Antemortem diagnosis may 
be difficult. • Some infectious agents may 
pose a public health risk.
Complete AV block may require pacemaker 
• If a specific pathogenetic agent is identified, 
appropriate, etiologically targeted therapy. 
• Tailor antiarrhythmic therapy based on 
ECG findings.
N/A.
• All antiarrhythmic drugs potentially have 
proarrhythmic properties and their effects 
should be closely monitored. • Systemic organ 
involvement (e.g., renal involvement) may 
necessitate modifying drug dosages. • Some 
agents that result in canine or feline myocarditis 
can also affect humans, so potentially there are 
public health considerations.
  FOLLOW-UP
• Antiarrhythmic therapy—frequent 
auscultation and ECG. • Serologic titers 
when appropriate. • Auscultation and 
follow ­up radiographs—treatment of heart 
failure. • Hemograms and serum biochemical 
analysis—systemic effects.
• Avoid breeding animals that have not been 
immunized. • Avoid endemic areas if possible.EXPECTED COURSE AND PROGNOSIS
• Depend on the extent and severity of 
myocardial involvement. • Many systemic 
fungal and protozoal diseases do not respond 
well to medical management. • Patients with 
extensive myocardial inflammation, 
degeneration, and signs of heart failure have a 
very poor prognosis. • Good prognosis if the 
underlying cause can be treated successfully.
Often accompanies systemic illness.
Viral myocarditis—most often seen in 
• Varies with infectious agent involved. 
• May be high with protozoal and mycotic 
Some viral diseases (e.g., canine herpesvirus 
and parvovirus) have been passed to the fetus 
during pregnancy.
SEE ALSO
• Aspergillosis, Disseminated Invasive. 
• Babesiosis. • Bartonellosis. • Blastomycosis. 
• Canine Distemper. • Canine Parvovirus. 
• Chagas Disease (American T rypanosomiasis). 
• Coccidioidomycosis. • Cryptococcosis. 
• Hepatozoonosis. • Idioventricular Rhythm. 
• Leishmaniosis. • Neosporosis. 
• Protothecosis. • Toxoplasmosis. • Ventricular 
Premature Complexes. • Ventricular 
Tachycardia.
• AIVR = accelerated idioventricular rhythm. 
• AV = atrioventricular. • CHF = congestive 
heart failure. • DCM = dilated 
cardiomyopathy. • ECG = electrocardiogram
Breitschwerdt EB, Atkins CE, Brown TT, et al. 
Bartonella vinsonii  subsp. berkhoffii  and 
related members of the alpha subdivision of 
the Proteobacteria in dogs with cardiac 
arrhythmias, endocarditis, or myocarditis. J 
Clin Microbiol 1999, 37(11):3618–3626.
Donovan TA, Balakrishnan N, Carvalho 
Barbosa I, et al. Bartonella  spp. as a possible 
cause or cofactor of feline endomyocarditis–
left ventricular endocardial fibrosis complex. 
J Comp Pathol 2018, 162:29–42.
Janus I, Noszczyk ­Nowak A, Nowak M, et al. 
Myocarditis in dogs: etiology, clinical and 
histopathological features (11 cases, 
2007–2013). Ir Vet J 2014, 67:1–8.
Author  Jonathan A. Abbott
P . Tilley.Myocarditis  (continued)

Canine and Feline, Seventh Edition  937
MMyoclonus
  BASICS
OVERVIEW
• Involuntary, rhythmic, or irregular muscle 
jerks. Can involve only a few adjacent muscles 
(focal), many or most muscles of the body 
(generalized), or many muscles in different jerks 
(multifocal) synchronously or asynchronously. 
• The myoclonic movements are spontaneous 
or activated by sensory stimulation (reflex 
myoclonus). •  May persist during sleep. 
• CNS dysfunction involving segmental lower 
motor neurons and interneurons of the spinal 
cord or the brainstem. •  Canine distemper 
virus infection—most frequent cause of 
myoclonus in dogs; thought to be secondary to 
some pacemaker activity in neurons damaged 
by the virus. May be caused by other 
encephalitides and degenerative processes 
affecting motor neurons.
Acquired
• Dog and rarely cat. •  No breed, sex, or age 
predispositions.
• Familial reflex myoclonus—Labrador 
retriever and Dalmatian; develops in the first 3 
weeks of life. •  Spongy degeneration of either 
gray and/or white matter—dogs: myoclonus of 
the paravertebral muscles in neonate silky 
terrier; Samoyed at 2 weeks; Saluki at 3 months; 
Labrador retriever at 4–6 months. Cats—  
Egyptian mau at 7 weeks. Rare syndromes.
SIGNS
• Canine distemper—after a bout of 
gastrointestinal signs, cough, and/or ocular or 
nasal purulent discharge; persists at rest and 
even during sleep or light anesthesia; 
consistent frequency in a given patient; 
distemper diagnosis may precede the 
myoclonus by months to years; occurs more 
frequently in chronic phase of distemper. 
• Familial reflex myoclonus—observed when 
the patient starts walking; intermittent 
muscle contractions induced by auditory or 
tactile stimulus and by exercise; involves all 
limbs, neck, and head (e.g., the facial and 
masticatory muscles); patient unable to rise 
without assistance. •  With spongy degeneration—  
variety of signs observed such as tremor, 
spasticity, opisthotonos, and myoclonus. 
• Chlorambucil-induced myoclonus reported 
in a cat with lymphoma.
• The patient may be otherwise healthy. 
• Masticatory and appendicular muscles—
most frequent affected muscles in distemper virus-induced myoclonus; may be paresis of 
the affected limb. •  May see other signs 
suggesting distemper (e.g., hard pads, ocular 
and nasal purulent discharge, and chorio -
retinitis). •  Neurologic deficits suggest 
multifocal lesions in some patients.
• Familial in Labrador retrievers. •  Spongy 
degeneration of unknown cause but likely 
inherited. 
Acquired
• Canine distemper virus—the only CNS 
disease repeatedly associated with myoclonus in 
dogs; unvaccinated dogs at risk. •  Encephalitis 
of any cause—dogs and cats. •  Degenerative 
disease—especially spongy degeneration. 
• Described in a dog with lead poisoning. 
• Total IV anesthesia with propofol. 
• Intrathecal administration of morphine. 
• T reatment with chlorambucil in cats.
  DIAGNOSIS
• The quickness of the jerks and the absence 
of voluntary influence help differentiating 
myoclonus from other movement disorders. 
• Congenital myoclonus—in neonates or 
during the first months of life in otherwise 
healthy dogs. Excitement, voluntary activity, 
and tactile/auditory stimuli often increase the 
myoclonus. •  Canine distemper virus—
unvaccinated dog; observed before, during, or 
after the acute CNS disease; more frequently 
observed later when the animal is otherwise 
healthy. Myoclonus involves one limb, more 
than one limb, the facial or the masticatory 
muscles. •  Lafora disease (progressive 
myoclonic epilepsy)—neurodegenerative 
disease that can cause myoclonic jerks. 
Differentiated on presence of other seizure 
types (generalized tonic–clonic seizures) and 
altered mentation. •  Myoclonic epilepsy—
jerks usually generalized, proximal more than 
distal, and flexor more than extensor; 
exacerbated by sensory stimulus (light, noise) 
and voluntary movements. Other types of 
seizures may be present concomitantly.
• Congenital or post canine distemper virus 
infection—normal. •  Other acquired 
forms—may suggest a specific cause if the 
patient has infectious encephalomyelitis; 
otherwise, normal.
IMAGING
MRI—may help determine diagnosis in acute 
acquired disease.DIAGNOSTIC PROCEDURES
Acute onset—CSF analysis, serologic testing, 
imaging to determine the cause if other 
physical or neurologic signs present. 
Electroencephalography and electromyo -
graphy—may help differentiate myoclonic 
epilepsy and peripheral nervous system 
disease from myoclonus.
  TREATMENT
• Active encephalomyelitis—inpatient; 
establish a diagnosis and initiate treatment. 
• Exercise—as tolerated. •  Diet—ensure 
proper nutrition with active CNS disease; 
modify, if necessary, with vomiting or 
diarrhea. •  Familial reflex myoclonus—
clinical signs in Labrador retriever and 
Dalmatian are severe and usually not 
compatible with quality of life.
• With chronic, inactive canine distemper—
treatment often unnecessary; alleviation may 
be obtained with procainamide 125–250 mg/
dog PO q6–12h. •  Gabapentin 10–20 mg/kg 
q8h reported beneficial in tremor syndrome. 
• Clorazepate 0.6–2 mg/kg PO q8h—familial 
reflex myoclonus; may see improvement. 
• Active encephalomyelitis—treat accordingly.
  FOLLOW-UP
• Monitor CNS disease. •  Myoclonus usually 
persists indefinitely; spontaneous remission 
may occur. •  Active distemper virus infection—  
poor-to-grave prognosis. •  Chronic 
distemper—myoclonus persists but patient 
otherwise healthy.
Cattai A, Rabozzi R, Natale V, et al. The 
incidence of spontaneous movements 
(myoclonus) in dogs undergoing total 
intravenous anaesthesia with propofol. Vet 
Anaesth Analg 2015, 42(1):93–98.
involuntary movements in dogs: myoclonus 
and myotonia. J Vet Intern Med 2017, 
31(4)979–987.

938  Blackwell’s Five-Minute Veterinary Consult  
MMyopathy—Hereditary X-linked Muscular Dystrophy
  BASICS
OVERVIEW
• Muscular dystrophy is an inherited, 
progressive and degenerative, generalized 
myopathy. Most muscular dystrophies are due 
to mutations in genes that code for muscle 
membrane associated proteins in the dystrophin–  
glycoprotein (DAG) complex. • Most 
common form in dogs occurs as a result of a 
deficiency of the protein dystrophin. 
• Muscular dystrophy due to dystrophin 
deficiency has an X-linked mode of inheritance 
and affected animals are predominantly male. 
• Dystrophin deficiency—identified first in 
golden retrievers. Subsequently, cases have 
been reported in many other dog breeds. 
Sporadic cases in other breeds are likely. • The 
dystrophin gene is large and new mutations are 
likely to occur. • Hypertrophic muscular 
dystrophy associated with dystrophin 
deficiency also occurs in domestic shorthair 
cats. • Deficiency of other muscle-associated 
proteins, e.g., alpha2 laminin (merosin) and 
sarcoglycan, has been identified more recently 
in dogs and cats and is not necessarily X-linked 
(females affected). • A myopathy associated 
with loss of alpha-dystroglycan with an 
autosomal recessive mode of inheritance occurs 
in young Devon Rex and Sphynx cats. Alpha-  
dystroglycan expression, which is associated 
with COLQ  anchorage at the motor end-plate, 
has been shown to be deficient in affected cats, 
resulting in a congenital myasthenic syndrome. 
• Unclassified muscular dystrophies have also 
been reported in other dogs (males and females).
• Seen primarily in neonate and young dogs (<1 
year). • Described in cats. • Muscular dystrophy 
due to dystrophin deficiency primarily affects 
males. • Several dog breeds known to be 
affected. Best described in golden retrievers. 
• Females—usually carriers of dystrophin gene 
defect, but dystrophin-deficient females may 
exhibit muscle weakness, tremors, limb 
deformities, and exercise intolerance. • Muscular 
dystrophy due to other muscle protein or 
unclassified defects may be seen in young male 
or female dogs and cats of any breed.
SIGNS
Dogs
• Golden retrievers—exercise intolerance; 
stilted gait; bunny-hopping pelvic limb gait; 
plantigrade stance; partial trismus; muscle 
atrophy (especially the truncal and temporalis 
muscles); hypertrophy of some muscles 
(especially the tongue); kyphosis; lordosis; 
drooling; dysphagia; aspiration pneumonia (due 
to pharyngeal and/or esophageal involve  ment). 
• Other breeds—similar; include vomiting and megaesophagus. • Abnormalities vary in 
severity, onset, and progression; may be seen as 
early as 6 weeks; tend to stabilize by 6 months. 
• Stunting and ineffective suckling—may be 
evident in younger pups. • Cardiac failure—
may occur owing to cardiomyopathy. • Severe 
muscle contractures may develop. • Spinal 
reflexes—normal initially; may become 
hypoactive.
Cats
• Dystrophin deficient—muscle hypertrophy; 
stiff gait; cervical rigidity; exercise intolerance; 
vomiting; may see calcified nodules on the 
tongue. • Usually young animals but not 
apparent in one cat until 21 months of age. 
• Other hereditary myopathies in cats may 
cause muscle atrophy; weakness; ventroflexion 
of the head and neck; dorsal protrusion of the 
scapulae with triceps brachii and dorsal 
cervical muscles most severely affected.
• Dystrophin deficiency—inherited defect of 
the X chromosome. • Other muscular 
dystrophies may not be X-linked. • Devon 
Rex/Sphynx myopathy—autosomal recessive.
  DIAGNOSIS
Other inherited myopathies such as centronu -
clear X-linked myotubular myopathies, 
infectious (especially protozoal), immune-  
mediated, or metabolic myopathies. 
Distinguished by muscle histology and 
demonstration of dystrophin deficiency or other 
muscle membrane protein associated deficiency.
• Dystrophin deficiency—normal except for 
marked elevation in serum creatine kinase 
(may be >10,000 U/L; further increased after 
exercise). Aspartate aminotransferase also 
likely to be elevated. • Other muscular 
dystrophies—creatine kinase may be normal.
• Muscle biopsy—dystrophin deficiency 
demonstrated by immunohistochemical 
evaluation of fresh frozen muscle; diagnostic. 
• Immunohistochemistry and immuno -
blotting analysis of muscle biopsy specimens 
can also assess abnormalities of other muscle 
proteins including dystrophin-associated 
proteins, laminin, sarcoglycan. • DNA tests 
available for specific genetic abnormalities in 
some breeds. • Serologic testing—may be 
warranted to rule out infectious and 
immune-mediated causes.
Electromyography—shows complex repetitive 
discharges.PATHOLOGIC FINDINGS
Histologic examination of muscle—muscle 
fiber necrosis and regeneration; myofiber 
mineralization (may be dramatic); myofiber 
hypertrophy (may be variation in myofiber 
size); fibrosis.
  TREATMENT
None proven effective.
Glucocorticosteriods—may provide some 
improvement; reason unknown. However, 
myofiber calcification increases, which may 
be deleterious.
  FOLLOW-UP
Monitor periodically for aspiration pneumo-
nia or cardiomyopathy.
• Discourage breeding of affected animals. 
• Do not repeat dam–sire matings that result 
in affected offspring. • Consider DNA testing 
of breeding animals where tests are available.
• Overall prognosis—guarded to poor as no 
effective palliative treatment. • Golden 
retrievers—signs tend to stabilize at 6 
months. • Other dog breeds and cats—
progression variable.
Dickinson PJ, LeCouteur RA. Feline 
neuromuscular disorders. Vet Clin North 
Am Small Anim Pract 2004, 
34(6):1307–1359.
Gandolfi B, Grahn RA, Creighton EK, et al. 
COLQ variant associated with Devon Rex 
and Sphynx feline hereditary myopathy. 
Anim Genet 2015, 46:711–715.
Shelton GD, Engvall E. Muscular dystrophies 
and other inherited myopathies. Vet Clin 
32(1):103–124.
Author  Georgina Child

Canine and Feline, Seventh Edition  939
M  BASICS
• Masticatory—focal inflammatory 
myopathy affecting the muscles of masti­
cation (temporalis, masseter, and pterygoid 
muscles) and sparing the limb muscles.
• Extraocular—selectively affects the extraocular 
muscles, sparing limb and masticatory muscles.
• Masticatory—suspected immune ­mediated 
cause owing to autoantibodies against type 
2M fibers and a positive clinical response to 
immunosuppressive doses of corticosteroids.
• Extraocular—suspected immune ­mediated 
cause owing to positive clinical response to 
Neuromuscular—muscles of mastication; 
extraocular muscles.
GENETICS
• Unknown.
• As with autoimmune diseases in general, the 
appropriate genetic background must exist.
• Masticatory—cavalier King Charles spaniels 
have a familial form and may be affected at 
less than 6 months of age.
• Extraocular—golden retrievers may have a 
• Unknown.
• Masticatory—relatively common.
Probably worldwide.
Species
• Dog (common).
• Cat (rare).
• Various.
• Masticatory—Rottweiler, Doberman, 
Samoyed, and cavalier King Charles spaniel 
develop severe forms.
• Extraocular—golden retriever.
No obvious age predisposition.
None obvious.
SIGNS
Masticatory—usually related to abnormalities 
of jaw movement, jaw pain, and masticatory 
muscle atrophy; not a “tabletop” diagnosis; 
usually requires laboratory testing to confirm 
• Masticatory—acute or chronic pain when 
opening the jaw; inability to pick up a ball or get food into the mouth; acutely swollen 
muscles; progressive muscle atrophy.
• Extraocular—bilateral exophthalmos.
• Masticatory—marked jaw pain with 
manipulation and/or trismus; acute muscle 
swelling with exophthalmos; muscle atrophy 
with enophthalmos; inability to open the jaw 
under anesthesia.
• Extraocular—bilateral exophthalmos; 
impaired vision.
CAUSES
Immune ­mediated.
• Possible previous bacterial or viral infection.
• Vaccination may exacerbate active disease.
  DIAGNOSIS
• Retro ­orbital abscess—probe behind last 
upper molar.
• Temporomandibular joint disease—
radiographically abnormal joint.
• Polymyositis—high serum creatine kinase 
activity; generalized electromyogram (EMG) 
abnormalities; diagnostic muscle biopsies.
• Neurogenic atrophy of temporalis muscles—
determined by EMG and muscle biopsy.
• Atrophy of masticatory muscles from 
corticosteroids—history of corticosteroid use; 
characteristic changes on muscle biopsy.
endocrine disorders—test for thyroid and 
adrenal disorders.
Serum creatine kinase activity—normal or 
mildly elevated.
• Muscle biopsy—diagnostic test of choice 
for masticatory muscle disease.
• Immunohistochemical assay—demonstrate 
autoantibodies against masticatory muscle 
type 2M fibers in frozen muscle biopsy 
sections; negative in polymyositis and 
extraocular disease.
• ELISA—demonstrate autoantibodies against 
masticatory muscle type 2M fiber proteins.
IMAGING
• Radiography of the temporomandibular joints.
• Orbital sonogram—for extraorbital disease; 
demonstrate swollen extraocular muscles.
• MRI—for demonstration of inflammation/
myonecrosis in muscles.
EMG—differentiate between extraocular 
disease and polymyositis; abnormal 
masticatory muscles in masticatory myositis 
only; generalized abnormalities including 
masticatory muscles in polymyositis.PATHOLOGIC FINDINGS
Masticatory
• Swelling or atrophy of the masticatory muscles.
• Biopsy specimen—may see myofiber necrosis, 
phagocytosis, mononuclear cell infiltration with 
a multifocal and perivascular distribution; may 
see myofiber atrophy and fibrosis with chronic 
condition; eosinophils rare.
Extraocular
Mononuclear cell infiltration—restricted to 
extraocular muscles
  TREATMENT
Gastrostomy tube—may be required with 
severe restrictions in jaw mobility; requires 
good hygiene and supportive care.
ACTIVITY
N/A
DIET
Masticatory—may require liquid food or 
gruel until jaw mobility is regained; may need 
a gastric feeding tube to facilitate fluid and 
caloric intake.
• Warn client that long ­term corticosteroid 
therapy may be required.
• Inform client that residual muscle atrophy 
and restricted jaw movement may occur with 
chronic masticatory muscle disease.
Corticosteroids—immunosuppressive 
dosages, tapered as jaw mobility, swelling, and 
serum creatine kinase activity return to 
normal; maintained at lowest alternate ­day 
dosage that prevents restricted jaw mobility; 
treated for a minimum of 6 months.
N/A
• Corticosteroids—watch for infection and 
undesirable side effects.
• Clinical signs may recur if treatment is 
stopped too soon.
N/A
Intolerable side effects of corticosteroids—
institute a lower dose of corticosteroids and 
combine with another drug (e.g., azathioprine).Myopathy—Masticatory and Extraocular Myositis

940  Blackwell’s Five-Minute Veterinary Consult  
• Masticatory—return of jaw mobility and 
decreased serum creatine kinase activity.
• Extraocular—decreased swelling of 
N/A
• Corticosteroids—undesirable side effects.
• Recurrence of clinical signs—treatment 
stopped too early.
• Poor clinical response—inadequate dosages 
of corticosteroids.
• Restrictive strabismus (extraocular myositis).
• Note position of tongue—venous 
congestion and tongue protrusion may occur 
• Masticatory—jaw mobility should return to 
normal unless the condition is chronic and 
severe fibrosis develops; good prognosis if 
treated early with adequate dosages of 
• Extraocular—good response to cortico­
steroids; good prognosis unless chronic with 
restrictive strabismus.
Other concurrent autoimmune disorders.AGE-RELATED FACTORS
N/A
N/A
Unknown
SYNONYMS
• Atrophic myositis.
• Eosinophilic myositis.
SEE ALSO
• Myopathy—Polymyositis and 
Dermatomyositis.
• Myopathy, Noninflammatory—Endocrine.
Allgoewer I, Blair M, Basher T, Davidson M. 
Extraocular myositis and restrictive 
strabismus in 10 dogs. Vet Ophthalmol 
2000, 3:21–26.
Carpenter JL, Schmidt GM, Moore FM, 
et al. Canine bilateral extraocular 
polymyositis. Vet Pathol 1989, 
26:510–512.
Melmed C, Shelton GD, Bergman R, 
Barton C. Masticatory muscle myositis: 
Pathogenesis, diagnosis, and treatment. 
Compend Contin Educ Pract Vet 2004, 
26:590–605.
Nanai B, Phillips L, Christiansen J, Shelton 
GD. Life threatening complication 
associated with anesthesia in a dog with masticatory muscle myositis. Vet Surg 2009, 
38:645–649.
Orvis JS, Cardinet GH III. Canine muscle 
fiber types and susceptibility of masticatory 
muscles to myositis. Muscle Nerve 1981, 
4:354–359.
Pitcher GDC, Hahn CN. Atypical mastica­
tory muscle myositis in three cavalier King 
Charles spaniel littermates. J Small Anim 
Pract 2007, 48:226–228.
Podell M. Inflammatory myopathies. Vet Clin 
North Am 2002, 31:147–167.
neurouscular diseases in dogs and cats. Vet 
Clin Pathol 2010, 39:278–295.
Shelton GD, Cardinet GH III, Bandman E. 
Canine masticatory muscle disorders: a 
clinicopathological and immunochemical 
study of 29 cases. Muscle Nerve 1987, 
10:753–766.
available onlineMyopathy—Masticatory and Extraocular Myositis  (continued)

Canine and Feline, Seventh Edition  941
MMyopathy, Noninflammatory—Endocrine
  BASICS
Myopathies associated with various endocrino­
pathies (including hypothyroidism, hyperthy­
roidism, hypoadrenocorticism, 
hyperadrenocorticism) and associated with 
exogenous corticosteroid use (steroid 
With Adrenal Dysfunction
• Glucocorticoid excess—impaired muscle 
protein metabolism; may accelerate 
degradation of myofibrillar and soluble 
protein in skeletal muscle; impairment of 
carbohydrate metabolism owing to induction 
of an insulin ­resistant state; may note elevated 
adrenocorticotropic hormone (ACTH) levels.
• Adrenal insufficiency—circulatory 
insufficiency; fluid and electrolyte imbalance; 
impaired carbohydrate metabolism.
With Thyroid Disease
• Hyperthyroidism—increased mitochondrial 
respiration; accelerated protein degradation 
and lipid oxidation; glycogen depletion; 
impaired glucose uptake.
• Hypothyroidism—impaired muscle energy 
metabolism by reduced glycogen breakdown, 
gluconeogenesis, and oxidative and glycolytic 
capacity; impaired insulin ­stimulated 
carbohydrate metabolism.
• Neuromuscular—impaired energy 
• Cardiovascular—impaired energy 
metabolism; circulatory disorders.
GENETICS
N/A
• Myopathies related to exogenous 
corticosteroids—common.
• Myopathies associated with Cushing 
syndrome and hypothyroidism—not 
uncommon.
Species
• Dog—steroid myopathy; weakness 
associated with hyperadrenocorticism and 
hypoadrenocorticism; hypothyroidism.
• Cat—weakness associated with hyper ­ 
Affects several breeds.
• Steroid myopathy—dogs of any age.
• Other disorders—see specific disease.Predominant Sex
None found.
SIGNS
Corticosteroid use in dogs—muscles very 
susceptible; muscle atrophy (particularly the 
masticatory muscles) is not uncommon with 
prolonged corticosteroid use.
• Muscle weakness, atrophy, and stiffness.
• Dysphonia.
• Muscle weakness, stiffness, cramping, and 
myalgia.
• Muscle hypertrophy or atrophy.
• May not note other clinical signs of an 
endocrine disorder.
CAUSES
• Endocrine dysfunction.
• Autoimmune.
• Neoplastic.
N/A
  DIAGNOSIS
• Inflammatory myopathies—distinguished 
by muscle biopsy.
• Noninflammatory myopathies—
distinguished by muscle biopsy.
• Baseline testing—abnormalities consistent 
with endocrine disorder.
normal, but may be mildly elevated if 
necrotic muscle fibers.
Thyroid and adrenal function tests—should 
be diagnostic.
IMAGING
• Dynamic studies—evaluate pharyngeal and 
esophageal function; with regurgitation and 
• Cardiac evaluation—for cats with hyper ­ 
• Muscle biopsy—fiber typing in fresh 
frozen muscle biopsy sections important, 
paraffin sections will not be diagnostic.
• Electromyography.
• Hyperadrenocorticism and steroid 
myopathies—selective atrophy of type 2 
muscle fibers; may see lobulated or ragged ­red 
fibers with associated myotonia.• Hypoadrenocorticism—muscle biopsies 
normal.
• Hyperthyroidism (cats)—muscle biopsies 
normal.
• Hypothyroidism—atrophy of type 2 fibers; 
may see an increase in type 1 fibers; may see 
periodic acid–Schiff (PAS) ­positive deposits 
and nemaline rod bodies.
  TREATMENT
Depends on specific endocrine disorder.
Physical therapy—with musculoskeletal 
manifestations.
ACTIVITY
• Clinical corticosteroid myopathy (humans)—  
inactivity worsens condition; increased 
muscle activity may partially prevent atrophy.
• Physical therapy—may help prevent and 
treat muscle weakness and wasting in dogs 
receiving glucocorticoids.
DIET
• Regurgitation and megaesophagus—feed 
from an elevation.
• Dysphagia and esophageal dilation—give 
food with the best ­tolerated consistency.
• Gastric feeding tube—if oral feeding is not 
tolerated.
Removal of neoplasia.
• Depends on specific endocrine disorder.
• Corticosteroid myopathy—decrease 
corticosteroid dosage to the lowest possible 
level; use a nonfluorinated corticosteroid and 
alternate ­day dosing.
• Intramyofiber lipid storage with steroid 
myopathy—l ­carnitine 50 mg/kg PO q12h 
may improve muscle strength.
N/A
Depend on specific endocrine disorder.
N/A
Fluorinated corticosteroids, triamcinolone, 
betamethasone, and dexamethasone—most 
likely to produce muscle weakness; use an 
equivalent dose of another corticosteroid.

942  Blackwell’s Five-Minute Veterinary Consult  
• Steroid myopathy—should note return of 
muscle strength and mass with decreased 
steroid use.
N/A
Depend on specific endocrine disorders.
• Myotonia associated with hyperadreno­
corticism—poor prognosis for resolution.
• Steroid myopathy—good prognosis for 
return of muscle strength and mass; recovery 
may take weeks.
• Hypothyroid myopathy—improvement in 
muscle pain and stiffness common.
• Hyperthyroidism (cats)—good prognosis 
for return of muscle strength following 
reversion to euthyroid state.• Hypoadrenocorticism—good prognosis for 
return of muscle strength.
• Dysphagia and regurgitation—may resolve 
with adequate treatment.
• May note multiple endocrinopathies.
• Hypothyroidism (dogs)—concurrent 
N/A
N/A
Unknown
• PAS = periodic acid–Schiff.INTERNET RESOURCES
Jaggy A, Oliver JE, Ferguson DC, et al. 
Neurological manifestations of hypothy­
roidism: a retrospective study of 29 cases. 
J Vet Intern Med 1994; 8:328–330.
LeCouteur RA, Dow SW, Sisson AF . 
Metabolic and endocrine myopathies of 
dogs and cats. Semin Vet Med Surg Small 
Anim 1989, 4:146–155.
Platt SR. Neuromuscular complications in 
endocrine and metabolic disorders. Vet Clin 
North Am 2002, 31:125–146.
Rossmeisl JH, Duncan RB, Inzana KD, et al. 
Longitudinal study of the effects of chronic 
hypothyroidism on skeletal muscle in dogs. 
Am J Vet Res 2009, 70:879–889.
Diane Shelton.Myopathy, Noninflammatory—Endocrine  (continued)

Canine and Feline, Seventh Edition  943
MMyopathy, Noninflammatory—Hereditary Labrador Retriever
  BASICS
OVERVIEW
• An inherited myopathy of Labrador 
retrievers. •  Recognized worldwide. 
• Autosomal recessive mode of inheritance; 
severity of clinical signs varies. •  More recently 
classified as a centronuclear myopathy (CNM). 
• The causative genetic mutation has been 
identified—called protein tyrosine phosphatase-
like A gene ( PTPLA ). CNM-causing genes, 
including PTPLA , interact to build a functional 
muscle and to maintain its homeostasis. •  Loss 
of tendon reflexes and muscle histology—may 
be more suggestive clinically of a neurogenic 
than a myopathic cause without further testing. 
No histologic abnormalities found in CNS or 
peripheral nervous system (PNS). •  Studies 
suggest PTPLA  mutation may have arisen 
spontaneously in one popular sire and is now 
disseminated widely in the Labrador 
• Occurs in black and yellow Labrador 
retrievers. •  Age of onset—variable (6 weeks–  
7 months); most commonly recognized at  
3–4 months. •  Affects males and females.  
• A similar inherited CNM has been identified 
in young male and female Great Danes.
SIGNS
• Severity ranges from stilted gait and exercise 
intolerance to severe muscle weakness, 
bunny-hopping pelvic limb gait, ventro -
flexion of the head and neck, arched back, 
and abnormal joint posture (cow-hocked 
stance, hyperextended carpi). •  Worsen with 
exercise, excitement, and cold weather. 
• Patient may collapse with forced exercise. 
• Some improvement with rest. •  Generalized 
muscle atrophy—mild to severe. •  Atrophy 
of proximal limb and masticatory muscles 
often most prominent. •  Tendon reflexes—
normal, hypoactive, or absent. •  Occasionally, 
patients become recumbent or develop 
megaesophagus.
Autosomal recessive mode of inheritance.
  DIAGNOSIS
• With little muscle atrophy—exercise 
intolerance may mimic signs of myasthenia 
gravis, cardiac or orthopedic disease. 
• Exercise-induced collapse syndrome also 
recognized in this breed; however, not 
associated with muscle atrophy and collapse seen only after strenuous exercise. •  With 
marked muscle atrophy—consider other 
myopathies (infectious, immune-mediated, 
metabolic, congenital) and generalized lower 
motor neuron disorders. •  Infectious 
myopathy due to congenital neospora 
caninum infection has a higher incidence in 
Labrador retrievers. •  Congenital muscular 
dystrophy in a male due to dystrophin 
deficiency and in a female due to sarcolemmal 
collagen deficiency myopathy have also been 
reported in Labrador retrievers. •  An X-linked 
myotubular myopathy (XLMTM), which is 
an unrelated CNM, due to a mutation in 
MTM1  gene, has also been identified in 
young male Labrador retrievers. Affected dogs 
show progressive and severe weakness and 
muscle atrophy in the first 2 months of life 
resulting in euthanasia before 6 months of age.
Creatine kinase—normal or mildly or 
moderately elevated.
A DNA test is available for the causative 
genetic mutation.
IMAGING
N/A
• Electromyogram (EMG)—spontaneous 
activity, including complex repetitive 
discharges, especially in proximal limb and 
masticatory muscles; may reveal no 
abnormalities with mild disease. •  Muscle 
histology—reveals variation in fiber size, 
angular atrophy of both type 1 and 2 
myofibers, grouped atrophy, increase in 
central nuclei, muscle degeneration and 
regeneration, and fibrosis; may note 
deficiency in type 2 myofibers or 
predominance of type 1 myofibers. •  DNA 
test for causative genetic mutation.
  TREATMENT
• None specific. •  Avoid cold, because it 
exacerbates clinical signs. •  DNA testing of 
breeding animals recommended. •  Discourage 
breeding of affected animals and parents and 
littermates of affected dogs. •  Do not repeat 
dam–sire matings that result in affected offspring.
Supplementation with l-carnitine 50 mg/kg 
PO q12h may be of benefit in improving 
muscle strength.CONTRAINDICATIONS/POSSIBLE 
  FOLLOW-UP
• Clinical signs generally stabilize at 
approximately 1 year of age. •  Mild disease—
may be an acceptable pet; may show some 
improvement in exercise tolerance. 
• Aspiration pneumonia—a risk in dogs with 
N/A
N/A
N/A
N/A
• CNM = centronuclear myopathy.
• EMG = electromyogram.
• PNS = peripheral nervous system.
• PTPLA  = protein tyrosine phosphatase-like 
A gene.
• XLMTM = X-linked myotubular myopathy.
Cosford KL, Taylor SM, Thompson L, 
Shelton GD. A possible new inherited 
myopathy in a young Labrador retriever. 
Can Vet J 2008, 49(4):393–397.
Maurer M, Mary J, Guillaud L, et al. 
Centronuclear myopathy in Labrador 
retrievers: a recent founder mutation in the 
PTPLA gene has rapidly disseminated 
worldwide. PLoS ONE 2012, 7(10): 
e46408.
McKerrell RE, Braund KG. Hereditary 
myopathy of Labrador retrievers. In: Kirk 
RW, Bonagura JD, eds., Current Veterinary 
Therapy X. Philadelphia, PA: Saunders, 
1989, pp. 820–821.
Schatzberg SJ, Shelton GD. Newly identified 
34(6):1497–1524.

944  Blackwell’s Five-Minute Veterinary Consult  
MMyopathy, Noninflammatory—Hereditary Myotonia
  BASICS
OVERVIEW
• Myotonia characterized by persistent 
contraction or delayed relaxation of muscle 
fibers on initiation of movement or when 
stimulated to contract.
• May affect all skeletal muscles.
• Myotonia may be congenital or acquired.
• A genetic basis has been determined in 
some breeds.
• Acquired myotonia may be associated with 
noninflammatory or inflammatory myopathy.
• Neuromyotonia and myokymia, characterized 
by continuous muscle fiber activity, are believed 
to be due to hyperexcitability of terminal nerve 
branches (neuromyotonia) or hyperexcitability 
of the motor nerve axon at any level (myoky -
mia) rather than a primary muscle disorder.
• Neuromyotonia is characterized by muscle 
stiffness and delayed relaxation.
• Myokymia describes rhythmic undulating 
muscle movements that produce a rippling 
movement of the skin.
• The cause of neuromyotonia and myokymia 
(continuous muscle fiber activity [CMFA]) in 
all reported cases remains unclear.
• CMFA and spinocerebellar ataxia may 
occur concurrently in Jack Russell terriers 
(JRTs) (and related breeds) and both are 
associated with a genetic mutation causing 
neuronal ion channel dysfunction.
• Congenital myotonia—chow chows, 
miniature schnauzers and Australian 
cattledogs; rarely seen in other dog breeds.
• Clinical signs seen when affected puppies 
begin to walk.
• Acquired myotonia—all breeds of any age 
potentially susceptible.
• Myotonia reported in young domestic cats.
• Neuromyotonia and myokymia (CMFA)—
described in predominantly young JRTs 
worldwide, rarely in other breeds, and a cat.
SIGNS
• Difficulty rising.
• Stiffness after rest or initiation of activity.
• May note dyspnea, voice change, 
 dysphagia, and/or regurgitation, especially 
after eating.
• May improve with exercise.
• May be exacerbated by cold.
• Muscle stiffness and myokymia observed in 
young JRTs may result in life-threatening 
hyperthermia. In this breed clinical signs are 
episodic but dogs may have continuous ataxia.
• Hypertrophy of proximal limb muscles, 
neck muscles, and tongue.
• Tongue may protrude from the mouth.
• Abduction of thoracic limbs.
• Stiff, stilted, pelvic limb gait.• Patient may fall and remain rigid in lateral 
recumbency for short periods. May become 
cyanotic.
• Affected miniature schnauzers may have 
craniofacial abnormalities such as mandibular 
shortening.
• Chow chows—suspected autosomal 
recessive mode of inheritance.
• Miniature schnauzers, Australian cattledogs—
(CLCN1  gene).
• JRT group CMFA and spinocerebellar 
ataxia—autosomal recessive mode of 
inheritance ( KCNJ10  gene).
  DIAGNOSIS
• Other myopathies—distinguished by 
signalment and clinical, electromyographic, 
and histologic findings.
• Hypertonicity disorders or other movement 
disorders—recognized breed association.
Creatine kinase—may be normal or slightly 
elevated.
DNA testing for known genetic mutations.
• Percussion of muscles and tongue—causes 
sustained dimpling.
• Electromyography—myotonia characterized 
by multifocal or generalized high-frequency 
discharges that wax and wane in amplitude and 
frequency (dive bomber sounding potentials) 
and are increased after muscle percussion. 
Myokymic discharges—rhythmic high-  
frequency bursts of single motor unit potentials 
are characteristic findings in myokymia.
• Muscle histology—congenital myotonia: 
normal or mild changes.
• Degenerative and/or inflammatory changes 
on muscle histology may be seen in cases of 
acquired myotonia.
• No abnormalities found on muscle biopsy 
in JRTs with neuromyotonia and myokymia 
(CMFA).
  TREATMENT
• Discourage activities that result in 
hyperventilation.
• Avoid strenuous exercise and excitement.
• Avoid cold.
• Anesthesia (induction and recovery)—  
possible risk of respiratory obstruction owing 
to adduction of vocal cords or regurgitation.  MEDICATIONS
• Membrane-stabilizing drugs—procainamide, 
quinidine, phenytoin, and mexiletine; may 
decrease severity of clinical signs.
• Procainamide reported to be most effective 
in chow chows. T reatment may decrease 
stiffness, stridor, and regurgitation, but gait 
remains abnormal.
• Extended-release procainamide 40–50 mg/kg 
q8–12h or mexiletine 8.3 mg/kg q8h reported 
to be effective in miniature schnauzers.
• Procainamide 10 mg/kg q8h or mexiletine 4 
mg/kg q12h or sustained-release phenytoin at 
an increasing dose 50–100 mg/kg for 6 weeks 
then on serum concentration monitoring 2–8 
mg/L reported to reduce frequency of episodes 
of CMFA in approximately half of affected 
JRTs, but response is generally temporary.
• Anesthesia and cooling to treat hyperthermia 
may be required to treat episodes of CMFA in 
JRTs.
Myotonia in humans is worsened with treatment 
with dantrolene, beta-adrenergic blocking 
agents, diuretics, and neuromuscular blocking 
agents. Bromide-containing agents such as 
potassium bromide may be contraindicated.
  FOLLOW-UP
• Chow chows, miniature schnauzers, 
Australian cattledogs—inherited condition; 
advise owner regarding breeding.
• DNA testing for carrier dogs prior to breeding.
• Do not repeat dam–sire matings that 
• Respiratory obstruction and/or aspiration of 
regurgitated food—may be life-threatening; 
advise owners of the clinical symptoms and 
• Hyperthermia associated with CMFA in 
JRTs is life-threatening.
Prognosis guarded.
• CMFA = continuous muscle fiber activity.
• JRT = Jack Russell terrier.
Vite CH. Myotonia and disorders of altered 
muscle cell membrane excitability. Vet Clin 
32(1):169–187.

Canine and Feline, Seventh Edition  945
MMyopathy, Noninflammatory—Hereditary Scottie Cramp
  BASICS
OVERVIEW
• Inherited disorder in Scottish terriers 
characterized by episodic muscle hypertonic-
ity or cramping.
• Not associated with any morphologic changes 
in muscle, peripheral nerve, or the CNS.
• Is better characterized as a hypertonicity 
disorder than a myopathy.
• Thought to be the result of a disorder in 
serotonin metabolism within the CNS.
• Similar condition (reflex myoclonus) 
reported in young Dalmatians and Labrador 
retrievers—may be result of low numbers of 
neurotransmitter glycine receptors in the CNS.
• Episodic muscle hypertonicity syndromes 
also occur in cavalier King Charles spaniels 
(episodic falling syndrome), Norwich terriers, 
bichon frises, border terriers (Spike’s disease 
or canine epileptoid cramping syndrome), 
Wheaten terriers, springer spaniels, and 
sporadically in other breeds.
• Young Scottish terriers, typically <1 year of 
age. Clinical signs may be seen in puppies as 
early as 6–8 weeks of age.
• No known sex predilection. Females may be 
SIGNS
• Normal at rest and on initial exercise.
• Further exercise or excitement—abduction 
of the thoracic limbs; arching (kyphosis) of 
the thoracolumbar vertebral column; 
stiffening or overflexion of the pelvic limbs 
(goose-stepping gait).
• Patient may fall, with tail and pelvic limbs 
flexed tightly against the body.
• Respiration—may cease for a short time.
• Facial muscles—may be contracted.
• No loss of consciousness.
• Severity varies. Generalized spasticity may 
be seen during episodes or only hind limb 
spasticity and skipping.
• Episodes—may last up to 30 minutes.
Inherited condition with probable autosomal 
recessive mode of transmission. Presence of 
dogs with cerebellar degeneration in the same 
pedigrees may suggest a more complex mode 
of inheritance than previously reported.
  DIAGNOSIS
• Seizure disorder—distinguished on basis of 
family history, typical clinical signs with no 
loss of consciousness, and induction of signs 
with serotonin antagonists.• Cerebellar cortical degeneration described 
in Scottish terriers—clinical signs are not 
episodic and neurologic abnormalities are 
slowly progressive.
Normal
DNA test available for episodic falling 
syndrome in cavalier King Charles spaniels. 
Genetic abnormality associated with other 
hypertonicity disorders not yet determined.
IMAGING
N/A
Diagnosis usually made on clinical presenta-
tion. Clinical signs may be induced by giving 
the serotonin antagonist methysergide 
(0.3 mg/kg PO). Cramping is evident in 2 
hours and may last for 8 hours.
  TREATMENT
Behavioral modification and/or environmen-
tal changes—eliminate triggering situations 
(excitement, stress); may be adequate in 
controlling episodes.
• Acepromazine maleate 0.1–0.75 mg/kg IM 
or PO, diazepam 0.5–1.5 mg/kg PO q8h, or 
vitamin E >125 U/kg q24h—may reduce the 
incidence and severity of Scottie cramp.
• Fluoxetine, a selective serotonin-reuptake 
inhibitor, may result in reduction in clinical 
signs. Recommended dose 1.2 mg/kg q12h 
initially followed by 0.8 mg/kg q12h. Clinical 
improvement has been maintained for >1 year 
• Clonazepam 0.5 mg/kg q8h may result in 
improvement in cavalier King Charles 
spaniels with hypertonicity syndrome 
(episodic falling syndrome).
• Serotonin antagonists—increase severity 
of clinical signs.
• Aspirin, indomethacin, phenylbutazone, 
flunixin meglumine (Banamine), and 
penicillin—may exacerbate clinical signs.
  FOLLOW-UP
NonprogressivePREVENTION/AVOIDANCE
• Discourage breeding of affected and related 
animals.
in affected offspring.
• Mild to moderate—fair to good long-term 
prognosis; usually manageable disability by 
owners; nonprogressive.
• Severe—guarded prognosis.
N/A
N/A
N/A
N/A
Geiger KM, Klopp LS. Use of a selective 
serotonin reuptake inhibitor for treatment 
of episodes of hypertonia and kyphosis in a 
young adult Scottish terrier. J Am Vet Med 
Assoc 2009, 235:168–171.
Meyers KM, Clemmons RM. Scotty cramp. 
In: Kirk RW, ed., Current Veterinary 
Therapy VIII. Philadelphia, PA: Saunders, 
1983, pp. 702–704.
Shelton GD. Muscle pain, cramps and 
hypertonicity. Vet Clin North Am Small 
Anim Pract 2004, 34(6):1483–1496.
Urkasemsin G, Olby NJ. Clinical 
characteristics of Scottie cramp in 31 cases. 
J Small Anim Pract 2015, 56:276–280.

946  Blackwell’s Five-Minute Veterinary Consult  
MMyopathy, Noninflammatory—Metabolic
  BASICS
• Myopathy associated with disorders of glycogen 
metabolism, lipid metabolism, or oxidative 
phosphorylation and mitochondrial metabolism.
• Currently poorly characterized in veterinary 
medicine.
• Usually associated with inherited or 
acquired enzyme defects involving major 
metabolic pathways.
• May result in storage of the abnormal 
metabolic byproduct or morphologic 
abnormalities of mitochondria.
• Cardiovascular—dependent on oxidative 
metabolism for energy.
• Hemic/lymphatic/immune—red blood cells 
(RBCs) depend on glycolytic metabolism.
• Nervous—dependent on glycolytic and 
oxidative metabolism for energy.
• Neuromuscular—dependent on oxidative 
• Storage products in other organs—liver, 
spleen.
GENETICS
Undetermined
Rare, except lipid-storage myopathies.
Unknown; probably worldwide.
Species
• Muscle phosphofructokinase deficiency—
spaniel, whippet.
• Acid maltase deficiency—Lapland dog.
• Branching enzyme deficiency—Norwegian 
forest cat.
• Debranching enzyme deficiency—German 
shepherd dog, Akita, curly-coated retrievers.
• Pyrvuate dehydrogenase phosphatase 1 
deficiency—Clumber spaniel, Sussex spaniel.
• Mitochondrial myopathy—Old English 
sheepdog, Yorkshire terrier, possibly Jack 
Russell terrier.
• Inherited metabolic defects—2–3 months.
• Acquired metabolic defects—adults.
SIGNS
Very few of these conditions have been 
adequately described.Historical Findings
• Muscular weakness.
• Cramping.
• Regurgitation and/or dysphagia.
• Esophageal and/or pharyngeal abnormalities.
• Dark urine; myoglobinuria, hemoglobinuria.
• Encephalopathy.
• Exercise-related weakness, stiffness, and/or 
cramping.
• Abnormal neurologic examination—
disorientation; stupor; coma.
• Abdominal distention—storage product 
accumulation in liver.
• May appear normal, with fluctuating 
CAUSES
• Inborn error of metabolism.
• Acquired metabolic defect.
• Viral infections.
• Drug-induced.
• Environmental factors.
• Inherited disorders.
• Others unknown.
  DIAGNOSIS
• Inflammatory myopathies—differentiated 
• Other noninflammatory myopathies—
differentiated by muscle biopsy.
• Other metabolic encephalopathies—
differentiated by laboratory evaluation.
• Plasma lactate and pyruvate levels—elevated 
resting or post exercise with disorders of fatty 
acid oxidation or oxidative phosphorylation; 
no elevation with glycolytic disorders.
• Serum creatine kinase activity—may be 
elevated with exercise and normal at rest; may 
be persistently elevated.
• Hypoglycemia—may occur with some 
glycolytic and oxidative disorders.
• Hyperammonemia—may occur with urea 
cycle defects.
• Quantitation of plasma amino acids—
abnormal accumulations.
• Quantitation of urine organic acids—
demonstrate abnormal organic acid 
• Quantitation of plasma, urine, and muscle 
carnitine—may be low with primary or 
secondary disorders of carnitine; low with 
primary organic acidurias.• Specific enzyme assays—depend on 
suspected metabolic defect.
• Fibroblast cultures—study metabolic defect.
• DNA-based tests to identify affected dogs 
and carriers when available.
IMAGING
MRI—evaluate the CNS; reveals abnormali-
ties in humans.
• Light microscopy—fresh frozen muscle 
sections; demonstrates storage products 
(glycogen, lipid) or abnormal mitochondria.
• Electron microscopy of muscle reveals 
abnormal mitochondria, paracrystalline 
inclusions, and glycogen or lipid accumulation.
• Cardiovascular system evaluation—may 
have concurrent cardiomyopathy.
• Other organ biopsies—with organomegaly.
• T riglyceride droplets in muscle—lipid 
storage myopathy.
• Ragged-red fibers in muscle—mitochondrial 
myopathy.
• Glycogen deposition in muscle—glycogen 
storage disorder.
  TREATMENT
• Inpatient—may require intensive care for 
severe encephalopathy, seizures, lactic 
acidemia, hypoglycemia, or hyperammonemia.
• Outpatient—clinical signs related only to 
neuromuscular system.
Depends on type and severity of disorder.
ACTIVITY
Exercise restriction—with muscle weakness, 
stiffness, or exercise-induced collapse.
DIET
• Avoid prolonged periods of fasting.
• Restrictions—depend on underlying defect.
• Vitamin and co-factor therapy—
determined by underlying defect.
• Warn client that most inherited metabolic 
defects cannot be cured, although some can 
be treated.
• Advise against breeding affected individuals.
N/A
• Depend on the abnormality and clinical 
signs.

Canine and Feline, Seventh Edition  947
M• Lipid storage myopathies—l-carnitine 
50 mg/kg PO q12h; riboflavin 50–100 mg 
PO q24h; coenzyme Q10 1 mg/kg PO q24h.
• Mitochondrial myopathies—may benefit 
from therapy similar to that listed for lipid 
storage myopathies.
Avoid fasting and strenuous exercise if they 
precipitate clinical signs.
N/A
N/A
  FOLLOW-UP
• Lipid storage myopathies—return of 
muscle strength; elimination of muscle pain.
• Elevated serum creatine kinase—should 
return to normal.
N/A
Severe neurologic impairment.
• Untreatable disorder—poor prognosis.• Lipid storage myopathies—good prognosis 
if no underlying organic academia.
• Iatrogenic and naturally occurring Cushing 
syndrome.
• Lipid storage myopathies—found in some 
dogs.
• Hemolytic anemia—due to underlying 
metabolic defect.
• Inborn errors—usually found in young 
dogs.
• Acquired defects—found in adult dogs.
N/A
Unknown
SYNONYMS
• Acid maltase deficiency—glycogenosis 
type II.
• Cori disease—glycogenosis type III.
• Glycogen storage disorders.
• Lipid storage myopathies.
• Mitochondrial myopathies.
• Phosphofructokinase deficiency—
glycogenosis type VII.
• RBC = red blood cell.INTERNET RESOURCES
• Comparative Neuromuscular Laboratory: 
• PennGen: http://vet.upenn.edu/
researchcenters/penngen
• VetGenLLC: http://www.vetgen.com/
Cameron JM, Maj MC, Levandovskiy V, 
et al. Identification of a canine model of 
pyruvate dehydrogenase phosphatase 1 
deficiency. Mol Genet Metab 2007, 
90:15–23.
Fyfe JC. Molecular diagnosis of inherited 
neuromuscular disease. Vet Clin North Am 
2002, 31:287–300.
Gerber K, Harvey JW, D’Agorne S, et al. 
Hemolysis, myopathy, and cardiac disease 
associated with hereditary phosphofructoki-
nase deficiency in two Whippets. Vet Clin 
Path 2009, 38:46–51.
Shelton GD. Canine lipid storage myopathies. 
In: Bonagura JD, Kirk RW, eds., Current 
Veterinary Therapy XII. Philadelphia, PA: 
Saunders, 1995, pp. 1161–1163.
North Am 2002, 31:103–124.
Diane Shelton.(continued)  Myopathy, Noninflammatory—Metabolic

948  Blackwell’s Five-Minute Veterinary Consult  
MMyopathy—Polymyositis and Dermatomositis
  BASICS
• Polymyositis—a condition in which skeletal 
muscles are damaged by a nonsuppurative 
inflammatory process dominated by 
lymphocytic infiltration. Terminology 
restricted to the immune-mediated form.
• Dermatomyositis—polymyositis is 
associated with characteristic skin lesions.
• Inflammation of skeletal muscles—results in 
muscle weakness, stiffness, myalgia, and atrophy.
• Muscle inflammation—may be a result of 
immune-mediated, infectious, or paraneo  -
plastic disorders; may be a sequela to certain 
drug therapies.
• Gastrointestinal—particularly the pharyngeal 
and esophageal muscles, because they are 
composed predominantly of skeletal muscle 
in dogs.
• Neuromuscular—generalized muscle 
involvement including masticatory and limb 
muscles.
• Skin/exocrine—particularly if related to a 
generalized immune-mediated connective tissue 
disorder. Skin lesions predominate over neuro -
muscular signs in canine dermatomyositis.
GENETICS
• Unknown.
• As for autoimmune diseases in general, the 
• Familial form of autoimmune polymyositis 
in Newfoundland and vizsla.
• Dermatomyositis—reported to have an 
autosomal dominant inheritance pattern in 
rough-coated collie and Shetland sheepdog.
• Unknown.
• Generalized inflammatory myopathies—not 
common but recognition may be increasing.
Species
Dog and rarely cat.
• Polymyositis—various breeds of dogs and 
cats may be affected; breed-associated in 
Newfoundland, boxer, and vizsla.
• Dermatomyositis—reported in rough-
coated collie, Shetland sheepdog, and 
Australian cattle dog.
• Polymyositis—none obvious.
• Dermatomyositis—3–5 months of age.Predominant Sex
SIGNS
• Polymyositis—usually associated with a 
stiff-stilted gait, variable myalgia, and/or 
muscle weakness. May see regurgitation and 
• Elevated serum creatine kinase activity—
supports but does not make the diagnosis of 
myositis. Do not rule out polymyositis if 
creatine kinase activity normal.
• Muscle biopsy—needed to confirm the 
• Stiff-stilted gait—acute or chronic.
• Muscle swelling and/or atrophy.
• Variable muscle pain.
• Generalized muscle weakness and exercise 
• Regurgitation of food or difficulty 
• Variable pain upon palpation of muscle groups.
• Generalized muscle atrophy, including the 
muscles of mastication.
• Gait abnormalities, including a stiff-stilted 
gait.
• Neurologic examination—not abnormal; 
may be a decreased gag reflex if the pharyngeal 
muscles are affected.
• Dermatomyositis (dogs)—typical skin 
lesions.
CAUSES
• Infections— Toxoplasma gondii ; Neospora 
canis; Sarcocystis  spp.; tick-related diseases, 
bacterial infection uncommon.
• Paraneoplastic or pre-neoplastic syndrome.
• Possibly previous bacterial or viral infection.
• Neoplasia, possibly occult.
• Exposure to ticks.
  DIAGNOSIS
• Polyarthritis—differentiated by physical 
examination and evaluation of joint fluid.
• Noninflammatory muscle disorders—
• Polyneuropathy—differentiated by 
neurologic examination, electrophysiology, 
and muscle and peripheral nerve biopsies.
• Chronic intervertebral disc disease—
differentiated by neurologic examination and 
serum creatine kinase activity.• Myasthenia gravis—differentiated by 
positive acetylcholine receptor (AChR) 
antibody titer.
Serum creatine kinase activity—variably 
elevated.
• Serum antinuclear antibody titer—may be 
positive in connective tissue disorders.
• May see concurrent hypothyroidism.
• Cardiac troponin I—may have concurrent 
myocarditis.
IMAGING
• Regurgitation—evaluate thoracic radiography 
for esophageal dilatation, neoplasia.
• Cardiac silhouette—evaluate myocardial 
size and shape.
• Pharyngeal weakness—perform a dynamic 
study for the evaluation of the swallowing 
process.
• Muscle biopsy—single most important test 
for diagnosing polymyositis; sample multiple 
muscles, because condition may be missed if 
distribution is patchy.
• Echocardiograph—evaluate myocardial 
function.
• Electrodiagnostic evaluation (electromyogram 
[EMG], measurement of nerve conduction 
velocity)—performed to determine the 
distribution of muscle involvement and the 
muscles to be biopsied; should help 
differentiate myopathic from neuropathic 
causes of muscle weakness.
• Muscle swelling or atrophy.
• Biopsy specimens—usually contain 
mononuclear cell infiltrates.
• Rare neutrophils or eosinophils—may be 
noted.
• Regenerating myofibers—may be 
observed.
• Intramyofiber parasite cyst—rare.
• Chronic condition—may see extensive 
myofiber atrophy and fibrosis.
  TREATMENT
Supportive care—may be required to 
prevent skin wounds and decubital ulcers 
in nonambulatory, severely affected patients.
ACTIVITY
Should increase, along with muscle strength, 
as muscle inflammation decreases.

Canine and Feline, Seventh Edition  949
MDIET
• Megaesophagus—may require feeding from 
an elevation; try foods of different consistencies.
• Severe regurgitation—may need to place a 
gastric feeding tube to maintain hydration 
and nutrition.
• Warn client that long-term immuno -
suppressive therapy may be required for an 
immune-mediated condition.
and contractures may occur with chronic 
disease and extensive fibrosis.
• Suggest genetic counseling for familial 
Only for concurrent neoplasia.
• Corticosteroids—immunosuppressive 
dosages usually result in clinical improvement 
of immune-mediated condition; decrease to 
the lowest alternate-day dosage that maintains 
normal creatine kinase activity and improved 
muscle strength and mobility; may require 
long-term therapy.
• Identified infectious agent—initiate specific 
therapy.
• Identified myocardial failure—initiate 
specific therapy.
N/A
Corticosteroids—observe for infection and 
undesirable side effects; remember that 
chronic therapy may lead to muscle atrophy 
(steroid myopathy).
institute a lower dose of corticosteroids 
combined with another drug 
(e.g., azathioprine, cyclosporine).
  FOLLOW-UP
• Serum creatine kinase activity—periodic 
evaluation; if elevated, should decrease into 
the normal range.
• Corticosteroids—side effects.
N/A
of corticosteroids. May need additional or 
alternative immunosuppressant.
• Immune-mediated condition—good to fair 
• Paraneoplastic disorder associated with 
occult neoplasia—guarded prognosis.
• Other concurrent autoimmune disorders.
N/A
N/A
UnknownSEE ALSO
Myopathy, Noninflammatory—Endocrine.
• AChR = acetylcholine receptor.
Evans J, Levesque D, Shelton GD. Canine 
inflammatory myopathies: a clinicopatho-
logic review of 200 cases. J Vet Intern Med 
2004, 18:679–691.
Haley AC, Platt SR, Kent M, et al. Breed-
specific polymyositis in Hungarian Vizla 
dogs. J Vet Intern Med 2011, 25:393–397.
Hargis AM, Haupt KH, Prieur DJ, Moore 
MP . A skin disorder in three Shetland 
sheepdogs: Comparison with familial canine 
dermatomyositis of collies. Compend 
Contin Educ Pract Vet 1985, 7:306–318.
Neravanda D, Kent M, Platt SR, et al. 
Lymphoma-associated polymyositis in dogs. 
J Vet Intern Med 2009, 23:1293–1298.
Shelton GD. From dog to man: the broad 
spectrum of inflammatory myopathies. 
Neuromusc Disord 2007, 17:663–670.
Warman S, Pearson G, Barrett E, Shelton 
GD. Dilatation of the right atrium in a dog 
with polymyositis and myocarditis. J Small 
Anim Pract 2008, 49:302–305.
available online(continued)  Myopathy—Polymyositis and Dermatomositis

950  Blackwell’s Five-Minute Veterinary Consult  
MMyxedema and Myxedema Coma
  BASICS
OVERVIEW
• Myxedema coma is a rare, life-threatening 
manifestation of severe hypothyroidism and 
an endocrine emergency.
• The development of myxedema coma 
requires a precipitating event (often infection) 
that overwhelms normal homeostatic 
• The greatest challenge with myxedema 
coma is recognition. Once recognized, 
immediate and intensive supportive care is 
necessary. Successful treatment requires 
treatment of the underlying cause, if present. 
Mortality rates can be high.
• Dogs.
• Median age—6 years.
• Female dogs predisposed.
SIGNS
• The most common findings are changes in 
mental status, altered thermoregulation, and 
nonpitting skin edema.
• Mentation changes are due to brain edema, 
ranging from altered alertness to obtundation. 
Mental depression is the most common 
mental status. Coma is rarely reported.
• Other signs consistent with hypothyroidism.
• Prior diagnosis of hypothyroidism.
• Hypothermia, nonpitting edema, tachypnea, 
alopecia, dehydration, dermatitis, otitis.
• Mental dullness is common and decreased 
postural reactions may be present.
• In humans, classic signs of myxedema coma 
include mental dullness, bradycardia, 
hypothermia, hypoventilation, and hypo -
tension. These signs have been reported in 
dogs, but most do not present with all of them.
• Myxedema coma results from chronic 
untreated severe primary hypothyroidism.
• Both forms of primary hypothyroidism 
(lymphocytic thyroiditis and idiopathic 
thyroid atrophy) have been associated with 
the development of myxedema coma.
• A secondary precipitating event is usually 
associated with the onset of a myxedema crisis.
• Precipitating events can include infections, 
respiratory disease, heart failure, and hypo  - 
volemia.
• Exposure to cold temperatures may be a 
precipitating event.  DIAGNOSIS
Weakness may be associated with cardio -
vascular disease, neurologic disease, and other 
• Mild nonregenerative anemia.
• Hypercholesterolemia.
• Urinalysis is normal.
• Thyroid function tests—severe hypo -
thyroidism with low total thyroxine (T4), low 
free T4, and elevated thyroid-stimulating 
• Blood gas analysis may note hypoxemia or 
• Diagnostics are aimed at identifying an 
IMAGING
Thoracic radiographs/ultrasound—
pulmonary alveolar pattern, pleural effusion 
(modified transudate).
Skin biopsies show dermal thickening, 
myxedema, and vacuolation of arrector pili 
muscles.
  TREATMENT
• Myxedema coma is a medical emergency.
• Once a presumptive diagnosis is made, 
immediate inpatient treatment is necessary.
• Due to the critical nature of myxedema 
coma, treatment must be initiated before 
thyroid function test results confirm 
• Immediate provision of a patent airway and 
resuscitation of hypotension are necessary.
• Mechanical ventilation may be necessary.
• IV fluid therapy to support blood pressure 
and to address hyponatremia. Patients with 
myxedema have a decreased ability to excrete 
free water.
• Replacement isotonic crystalloids 
(Normosol-R or lactated Ringer’s solution, 
20–30 mL/kg, IV initial bolus) are first-line 
therapy. Reassess and continue IV fluids 
(2.5–7 mL/kg/h) as necessary to maintain 
blood pressure and heart rate.
• IV administration of synthetic thyroid 
hormone.
• Rapid rewarming may cause peripheral 
vasodilatation, hypotension, and potential cardiovascular collapse; correction of hypo  - 
thermia should be passive and occur over a 
number of hours.
• Definitive immediate treatment—
levothyroxine 5 μg/kg (0.005 mg/kg) IV 
q12h.
• A more conservative dose should be used 
when there is concern about cardiac function, 
and the heart’s ability to deal with a rapid 
increase in metabolic rate. Decrease 
levothyroxine dose by 50–75% in these cases.
• Once the patient’s condition has stabilized 
and the patient is able to swallow, oral 
levothyroxine therapy should be initiated at 
0.02 mg/kg PO q12h.
• Lower IV levothyroxine dose in patients 
with cardiac disease.
• Avoid rapid rewarming.
  FOLLOW-UP
• Prognosis is guarded to grave.
• If patient survives initial treatment, treat and 
monitor as recommended for hypothyroidism.
SEE ALSO
Hypothyroidism.
• T4 = thyroxine, tetraiodothyronine.
Finora K, Greco DS. Hypothyroidism and 
myxedema coma in veterinary medicine—
physiology, diagnosis and treatment. 
Compend Contin Educ Pract Vet 2007, 
29:19–32.
Koenig A. Endocrine emergencies in dogs and 
cats. Vet Clin North Am 2013, 
43:869–897.
Pullen WH, Hess RS. Hypothyroid dogs 
treated with intravenous levothyroxine. J 
Vet Intern Med 2006, 20:32–37.

Canine and Feline, Seventh Edition  951
MMyxomatous Mitral Valve Disease
  BASICS
Myxomatous mitral valve disease (MMVD) is 
characterized by progressive myxomatous 
degeneration, which refers to a characteristic 
pathologic weakening and disorganization of 
valvular connective tissue. Although myxo­
matous degeneration most commonly affects 
the mitral valve, any of the four intracardiac 
valves can be affected, and the most com­
monly used descriptor “mitral” does not 
exclude involvement of other valves.
• Pathologic weakened and disorganized 
valvular connective tissue, in which the 
spongiosa component is unusually prominent 
with accumulation of mucopolysaccarides 
and glycosaminoglycans. •  Valve leaflets 
become thickened and elongated with disease 
progression. •  Degenerative changes in 
chordae tendineae lead to thickening and 
elongation of these structures, thus 
contributing to valve flattening and prolapse. 
• With progression, valve lesions cause 
insufficient systolic coaptation of the leaflets, 
leading to backward regurgitation of blood 
from the ventricle into the atrium. •  Severity 
of mitral regurgitation depends on severity of 
valve lesions (leaflets and/or chordae tendineae). 
• Compensatory mechanisms include cardiac 
dilation and eccentric hypertrophy, increased 
force of contraction, increased heart rate, 
increased pulmonary lymphatic drainage, 
fluid retention, and neurohormonal 
modulation of cardiovascular function. 
• With progression, valvular regurgitation 
eventually may not be compensated, leading 
to reduced cardiac output and increased 
venous pressures, leading to pulmonary 
edema if left ­sided congestive heart failure 
(CHF) and ascites if right ­sided CHF . 
• Acute cardiac tamponade may result from 
atrial tear.
• Cardiovascular—myxomatous degeneration 
most commonly affects the mitral valve but 
any intracardiac valve can be affected. 
• Hepatobiliary—passive congestion at 
advanced stages. •  Renal/urologic—prerenal 
azotemia at advanced stages. •  Respiratory—
if edema and/or pulmonary hypertension 
(PH) develops.
GENETICS
Etiology currently unknown, but the current 
leading scientific hypothesis is that a 
genetically determined dystrophic process 
initiates valve degeneration. Age of onset is 
inherited as a polygenetic threshold trait (i.e., 
multiple genes influence the trait and a 
certain threshold has to be reached before the 
disease develops). This mode of inheritance means that a combination of a sire and a dam 
that both have an early onset of MMVD will 
give offspring that have, on average, an early 
onset of the disease. A combination of dogs 
with late onset will give offspring that 
manifest the disease at old age or never.
The most common cardiac disease in dogs. 
Prevalence is strongly influenced by age: it is 
uncommon in young dogs but common in 
old dogs. MMVD is encountered in all 
breeds, but the highest prevalence is seen in 
small to medium ­sized dog breeds. The 
prevalence reaches >90% in some affected 
dog breeds >10 years.
Species
Dogs; extremely rare in cats.
Typically small breeds (<20 kg, but may be 
encountered in larger dogs), such as cavalier 
King Charles spaniel (CKCS), Chihuahua, 
miniature schnauzer, Maltese terrier, 
Pomeranian, cocker spaniel, Pekingese, 
poodle, and others.
Murmur may be detected from 2 years of age 
with a peak incidence for detection at 6–8 
years in widely affected breeds such as the 
CKCS. Onset of CHF from 8–12 years.
Males develop the disease at a younger age 
than females, which means higher prevalence 
at a given age in males,
SIGNS
Signs depend on the stage of disease. The 
descriptions here align with the grading 
system described in the American College of 
Veterinary Internal Medicine (ACVIM) 
consensus statement on MMVD.
Clinically Healthy Patients but at 
a Higher Risk of Developing the Disease 
(ACVIM Stage A)
No abnormal findings.
Dogs Diagnosed with the Disease but 
with No Overt Clinical Signs (ACVIM 
Stage B)
• Systolic click (early stage). •  Systolic 
murmur best heard over the mitral or 
tricuspid areas. •  Murmurs may range from 
soft low ­intensity to loud holosystolic. 
• With progression, murmurs typically get 
louder and radiate more widely. •  Initially, 
patients have no obvious radiographic or 
echocardiographic changes in cardiac 
chamber size or have mild cardiomegaly and 
do not meet the so called “EPIC trial criteria” 
(see ACVIM stage B1). Stage B2 is defined as 
dogs with cardiac enlargement meeting EPIC 
trial criteria, i.e., presenting a moderate or 
loud intensity murmur (≥3/6), VHS >10.5, bodyweight normalized left ventricular 
end­diastolic diameter (LVIDDn) ≥1,7, and a 
left atrial to aortic root ratio (LA/Ao) ≥1.6.
Dogs with Overt Clinical Signs of CHF or 
with Clinical Signs Stabilized by CHF 
Therapy (ACVIM stages C and D)
• Usually a loud holosystolic heart murmur. 
• Tachypnea/dyspnea/orthopnea if decomp­
ensated CHF . •  Tachycardia and loss of 
respiratory sinus arrhythmia if decompensated 
CHF . •  Arrhythmia, such as supraventricular 
premature beats, ventricular premature 
beats, or atrial fibrillation, may be present. 
• Respiratory crackles if decompensated CHF . 
• Weak femoral pulse, prolonged capillary 
refill time and pale mucous membranes in low 
output failure. •  Pink froth, i.e., pulmonary 
edema, may be evident in the nares and 
oropharynx in severe decompensated CHF . 
• Ascites if right ­sided CHF (caused by 
myxomatous tricuspid lesions and/or 
pulmonary hypertension [PH]).
CAUSES
Primary (inciting) factor unknown but the 
disease is influenced by genetic factors in 
affected breeds.
• Breed. •  Sex (males have earlier onset).
  DIAGNOSIS
• Bacterial endocarditis. •  Congenital heart 
disease. •  Dilated cardiomyopathy. 
• Chronic airway or interstitial lung disease. 
• Pneumonia. •  Pulmonary embolism. 
• Pulmonary neoplasia. •  Heartworm 
disease.
• CBC/biochemistry usually unremarkable 
unless severe disease and ongoing CHF 
therapy. •  Prerenal azotemia secondary to 
impaired renal perfusion; high urine specific 
gravity unless complicated by underlying 
kidney disease or recent/ongoing diuretics. 
• High liver enzyme activity in many patients 
with right ­sided CHF .
• Natriuretic peptides—often unremarkable 
unless moderate to severe disease. •  Serum 
troponin I—unremarkable unless severe 
disease.
IMAGING
• Heart size ranges from normal to left ­sided 
or generalized cardiomegaly. •  LA enlargement 
is usually the earliest finding. •  LV may be 
enlarged. •  Left­sided CHF—pulmonary 
congestion; increased interstitial pattern ± 
alveolar pattern with air bronchograms.

952  Blackwell’s Five-Minute Veterinary Consult  
MInitially, congestion and edema are perihilar, 
but all lungfields may eventually show 
changes.
• Thickened and distorted mitral valve 
leaflets. •  Elongated and ruptured chordae 
tendineae, causing mitral valve prolapse. 
• Normal to severely dilated atrium (uni ­ or 
bilateral). •  LV may be dilated and is 
hyperdynamic if regurgitant flow is significant 
and myocardial function intact; as LV 
becomes more grossly distended, it may 
become normo ­ or, uncommonly, hypo­
dynamic because of myocardial failure. 
• Pericardial effusion (usually mild) may be 
present in severe disease. •  Doppler studies 
show a jet of regurgitation into the atrium. 
• Doppler evaluation for the presence of PH 
should be routinely performed.
• Arterial/venous blood gases can be used to 
quantify hypoxemia and monitor treatment 
response. •  Systemic blood pressure should 
be monitored; especially patients receiving 
diuretics and other cardiovascular drugs to 
check for hypotension; hypertension is not 
associated with the disease, but if concurrent 
can exacerbate the disease.
• Sinus tachycardia common in patients with 
CHF . •  May show evidence of LA enlargement 
(P mitrale) or LV enlargement (tall and wide R 
waves). •  Supraventricular, or ventricular 
arrhythmias may develop in severe disease.
• Gross valvular changes range from only a 
few discrete nodules at the line of closure to 
gross distortion by gray ­white nodules and 
plaques causing contraction of the cusps and 
rolling of the free edge; the chordae are 
irregularly thickened, with regions of tapering 
and rupture. •  Mild disease—normal cardiac 
size. More progressed cases—LA and LV 
dilation. Degree of right ­sided dilatation 
variable. •  Degree of LV hypertrophy may be 
apparent only when weighing the heart. •  Jet 
lesions—irregular thickening and opacity of 
the atrial endocardium. •  LA splits or tears in 
  TREATMENT
Dogs with preclinical MMVD can be 
managed at home with scheduled rechecks to 
identify dogs that meet EPIC trial criteria for 
initiation of pimobendan. Some dogs with 
mild to moderate signs of CHF may be 
managed at home, whereas dogs with more 
severe signs should be hospitalized initially for 
intensive CHF therapy.NURSING CARE
Oxygen therapy as needed for hypoxemic dogs 
with moderate to severe CHF . Dogs receiving 
diuretics must be given the opportunity to 
urinate. Dyspnea ­associated anxiety should be 
treated. Carefully monitor blood pressure and 
respiratory response to narcotics and tranquilizers 
in the setting of acute decompensated CHF . 
Butorphanol 0.2–0.25 mg/kg IM or IV is 
commonly used for sedation, but combina ­
tions of buprenorphine 0.0075–0.01 mg/kg 
and acepromazine 0.01–0.03 mg/kg IV, IM, 
or SQ can also be used.
ACTIVITY
• Exercise restriction for symptomatic patients 
in acute decompensated CHF . •  Exercise 
recommended for stable CHF patients on 
medical therapy, but avoid strenuous exercise.
DIET
• Prevent cardiac cachexia by ensuring adequate 
calorie intake. •  Avoid high sodium diets.
• Discuss the progressive nature of the disease. 
• Mild disease severity is suggestive of a long 
period without clinical signs; moderate to 
severe disease indicates a shorter period until 
signs of CHF may develop. •  If a breeder, 
inform about the disease genetics and impact 
for future breeding. •  Pimobendan therapy 
prolongs preclinical period and survival times 
in dogs meeting the EPIC criteria. •  Appropriate 
level of exercise, but at the same time maintain 
quality of life. •  Common signs of CHF listed 
earlier. •  How to medicate (if indicated)—
information about consistent dosing and that 
diuretic doses should be adjusted in 
consultation with the veterinarian. •  Possible 
adverse side reactions of medications. •  How to 
monitor resting and/or sleeping respiratory 
rates at home, and at which rate new contact 
with the clinician should be initiated. •  Diet (if 
indicated)—emphasize importance of avoiding 
cardiac cachexia by paying close attention to 
appetite and using an appropriate diet. Salt 
loads should be avoided.
Surgical valve repair can be performed at a 
few sites in the world.
Recommended treatment depends on disease 
stage; these recommendations follow the 
guidelines set by the consensus statement 
developed by the ACVIM.
Patients without Overt Clinical Signs 
(ACVIM Stage B)
• If no cardiomegaly, no treatment currently 
recommended. •  Pimobendan 0.25–0.3 mg/kg q12h PO prolongs preclinical period (by a 
median of approximately 15 months) and 
survival in Stage B2 dogs. •  Administering 
angiotensin ­converting enzyme inhibitors 
(ACEIs) to Stage B patients has been shown 
to be ineffective in two clinical trials.
Patients Showing Overt Clinical Signs 
(ACVIM Stages C and D)
Acute Decompensated CHF
• Furosemide IV, SC, IM, or PO; dose is 
dependent on severity of CHF: ◦ Mild to 
moderate CHF: 2–4 mg/kg q8–24h. ◦ Severe 
or fulminant CHF: 4–8 mg/kg q2–6h, 
preferably IV, IM, or SC. ◦ Monitor 
outcome of treatment by respiratory rate and 
general clinical status. ◦ Dose can often be 
reduced once the patient is stabilized. 
• Oxygen supplementation and cage rest to 
patients with significant dyspnea: 40% in O2 
cage (can intermittently go as high as 100%) 
up to 24 hours; nasal O2 may be used in 
large­breed dogs, 50–100 mL/kg/min 
through humidifier. •  Pimobendan 0.25–0.3 
mg/kg q12h PO. In many countries outside 
of the United States, IV pimobendan is 
available and used as an initial single ­dose 
treatment before oral medication. 
• Additional options in severe fulminant 
CHF: ◦ Nitroglycerin: ointment (one ­fourth 
inch/5 kg up to 2 inches percutaneously), 
sublingual spray (one puff/10 kg) or 
injectable (1–5 μg/kg/min CRI). ◦ Arterial 
vasodilator to decrease afterload rapidly, e.g., 
hydralazine 0.5 mg/kg q12h (titrate up to 2 
mg/kg if necessary) or sodium nitroprusside 
1–10 μg/kg/min (expensive drug and difficult 
to obtain). Both drugs require blood pressure 
monitoring and should be considered only in 
hospitalized dogs under care of a specialist. 
◦ Dobutamine—dogs: 1–10 μg/kg/min; cats: 
1–5 μg/kg/min. •  Antiarrhythmics—as 
needed. •  Severe ascites may require 
abdominocentesis.
Chronic CHF (Typically Treated 
as an Outpatient)
• Exact composition of medical therapy 
depends on disease severity and clinical signs. 
All dogs with CHF require life ­long treatment 
with a diuretic, such as furosemide: ◦ Mild to 
moderate CHF: 1 mg/kg q12h to 2 mg/kg 
q8h PO. ◦ Moderate to severe CHF: 2–3 
mg/kg q12h or higher. •  Pimobendan at 
0.25–0.3 mg/kg q12h PO. •  ACEI (e.g., 
enalapril, benazepril, ramipril)—dose and 
frequency depend on ACEI used, e.g., 
enalapril 0.5 mg/kg q12–24h; benazepril 
0.25–0.5 mg/kg q24h. •  Spironolactone 2 
mg/kg q12–24h PO and/or hydrochlorothi­
azide at 2–4 mg/kg q12h PO. •  Digoxin 
0.22 mg/m2 q12h PO, or lower. 
• Antiarrhythmics—as needed. •  Sildenafil 
1–2 mg/kg q8–12h if PH present.Myxomatous Mitral Valve Disease  (continued)

Canine and Feline, Seventh Edition  953
MPRECAUTIONS
• Use digoxin, diuretics, and ACEIs 
cautiously in patients with renal disease. 
• Beta blockers are negative inotropes and 
may have an acute adverse effect on 
myocardial function and clinical status.
• Furosemide potentiates the effects of 
ACEIs, spironolactone, or thiazides. •  Use 
nonsteroidal anti ­inflammatory drugs 
cautiously in patients receiving furosemide or 
ACEIs.
• Diuretics—add thiazide and/or 
spironolactone in refractory animals. 
• Torsemide—administered at approximately 
1/10th of the furosemide dose, or 0.1–0.6 
mg/kg once to twice daily is an alternative to 
furosemide. •  Vasodilators—isosorbide 
dinitrate can be used in place of nitroglycerin 
ointment in patients requiring long ­term 
nitrate administration.
  FOLLOW-UP
• Frequency of rechecks depends on stage of 
MMVD and severity of CHF (if present). 
• Dogs without signs of CHF: ◦ Mild to 
moderate disease—perform echocardiography 
when a murmur is first detected and every 
6–12 months (interval depends on findings of 
previous echocardiogram) thereafter to 
document progressive cardiomegaly. Baseline 
radiographs may be useful. ◦ Owners are 
instructed to regulary measure respiratory rates 
at home during rest or sleep and contact the veterinarian should rates be consistently higher 
than 30 breaths/minute. •  Dogs with signs of 
CHF: ◦ Once acute CHF has been 
successfully treated, dogs can be treated at 
home. ◦ Follow ­up with owner, by phone or 
email, should be conducted after 1–3 days at 
home, to monitor for maintained treatment 
effect. A change in the furosemide dose (partly 
based on respiratory rates during sleep or deep 
rest and amount of side effects of the treatment 
initiated) may be performed. ◦ Reexamine after 
1–2 weeks (check for signs of decompensated 
CHF , dehydration, electrolyte imbalance, renal 
dysfunction, and presence of complications) or 
sooner if treatment response is unsatisfactory. 
◦ Thereafter once every 3–6 months if the 
patient is stable on the medications. More 
severe cases may require more frequent 
monitoring. •  Monitor BUN and creatinine 
especially when high doses of diuretics and 
ACEIs are used. •  Monitor potassium, 
especially if combinations of spironolactone, 
ACEIs, and digoxin are used.
• Preclinical patients may develop acute CHF . 
• Recurrent decompensated CHF in patients 
stabilized by medical therapy. •  PH. 
• Biventricular CHF in dogs with initial 
left­sided CHF . •  Mild pleural and/or 
pericardial effusion. •  Arrhythmia. •  Rupture 
of major chordae tendineae, leading to a flail 
valve leaflet and acute decompensation. 
• Atrial tear leading to acquired atrial septal 
defect or cardiac tamponade.
Valve lesions are progressive in nature and 
myocardial function may worsen, requiring 
increased drug dosages. Long ­term prognosis depends on response to therapy and stage of 
heart disease.
SYNONYMS
• Chronic valvular disease (CVD). •  Chronic 
mitral valve disease. •  Degenerative valvular 
disease. •  Degenerative mitral valve disease 
(DMVD). •  Degenerative valve disease.
SEE ALSO
• Atrial Wall Tear.
• ACVIM = American College of Veterinary 
Internal Medicine.
• LV = left ventricle.
• MMVD = myxomatous mitral valve disease.
Keene BW, Atkins CE, Bonagura JD, et al. 
ACVIM consensus guidelines for the 
diagnosis and treatment of myxomatous 
mitral valve disease. J Vet Intern Med 2019, 
33(3):1127–1140.
Authors  Ingrid Ljungvall and Jens 
Häggström
Consulting Editor  Michael Aherne(continued)  Myxomatous Mitral Valve Disease

954  Blackwell’s Five-Minute Veterinary Consult  
NNarcolepsy and Cataplexy
  BASICS
OVERVIEW
Narcolepsy/cataplexy refer to the same 
disorder, cataplexy being the clinical sign 
easiest to recognize in domestic animals.
Narcolepsy
• Sleep disorders. •  Syndrome characterized 
by excessive sleepiness, cataplexy sleep 
paralysis, and hypnagogic hallucinations 
(humans). Sudden episodes of paradoxical 
sleep without a preceding period of slow-wave 
sleep.
Cataplexy
• Sudden, episodic, and spontaneous collapse 
secondary to complete atonia of skeletal 
muscles (flaccid paralysis) caused by 
inhibition of spinal cord lower motor 
neurons. •  Patient stays alert and will follow 
with its eyes.•  Most common clinical sign of 
narcolepsy in small animals.
• Dog and rarely cat. •  Proven hereditary—
Labrador retriever, dachshund, and 
Doberman pinscher. •  Autosomal recessive 
gene mutation— canarc-1  gene found on 
chromosome 12, which codes for a 
hypocretin (orexin) receptor. Mutations of 
OxR2  (type II orexin receptor gene). 
Increased microglial expression of MHC II in 
Doberman pinscher. •  Assumed genetic basis 
for miniature poodle—mode of inheritance 
unknown. •  For inherited disease, clinical 
signs appear between 2 and 4 months of age 
with escalation of signs around 1 year of age. 
Possible disappearance of clinical signs later in 
life. •  Acquired form may develop in older 
animals (possible depletion of hypocretin 
production by hypothalamus) and can occur 
in any dog breed or mixed breed, at any age. 
• Clinical signs in acquired form will usually 
remain for life.
SIGNS
• Physical and neurologic examinations—
normal except during an episode. •  Onset—
peracute. •  Excessive daytime sleepiness and 
fragmented sleep patterns reported in 
domestic animals, but cataplexy is usually 
the clinical sign recognized by owners. 
• Cataplexy episodes—acute onset of flaccid 
paralysis without loss of consciousness 
lasting a few seconds to minutes (up to 20 
minutes) with sudden return to normal; 
multiple episodes in 1 day. •  Narcolepsy—
eye movements, muscular twitching, and 
whining (as in REM sleep) frequently 
observed during episodes. •  Patients are 
usually aroused by loud noises, petting, or 
other external stimuli.CAUSES & RISK FACTORS
• Hereditary in some breeds. •  Possible immune 
system involvement in acquired disease. 
• Neurotransmitter abnormalities—serotonin, 
dopamine, norepinephrine, neuropeptide 
hypocretin (orexin). •  Rarely reported with 
pontomedullary (brainstem) lesions. 
• Excitement, emotions, feeding, and general 
anesthesia may induce narcoleptic episodes.
  DIAGNOSIS
• Syncope. •  Seizure activity—urinary or 
fecal incontinence, excessive salivation and 
muscle rigidity are not characteristic of 
narcolepsy in which atonia predominates. 
Recovery after a narcoleptic event is 
immediate. •  Nonconvulsive seizure (drop 
attack). •  Neuromuscular disorders—onset of 
clinical signs usually not as sudden and 
recovery not immediate as in narcolepsy.
Normal
• DNA test for specific breeds (Labrador 
retriever, dachshund, and Doberman 
pinscher). •  CSF—normal. Low levels of 
orexin A in CSF . •  Standardized food-elicited 
cataplexy test; play-elicited cataplexy.
IMAGING
Brain MRI—normal.
• Observe an episode—if a consistent activity 
(feeding, excitement, etc.) elicits attacks, 
attempt to simulate the activity. •  Food-
elicited cataplexy test—place 10 pieces of 
food in a row 12–24 inches apart; record the 
time required for the patient to eat all the 
pieces and the number, type, and duration of 
any attacks that occur; normal dogs eat all 
food in <45 seconds and have no attacks; 
affected dogs take >2 minutes to eat the food 
and can have 2–20 attacks. •  Play-elicited 
cataplexy—2 dogs are left in a room and 
allowed to interact together and with toys. 
• Physostigmine (cholinesterase inhibitor) 
challenge to induce cataplexy in an affected 
dog—administer 0.025–0.1 mg/kg IV; repeat 
the food-elicited test 5–15 minutes after the 
injection; increase dosage if necessary 
(0.05 mg/kg, 0.075 mg/kg, 0.10 mg/kg); 
effects of each dose last 15–45 minutes.
  TREATMENT
• Primary goal—reduce the severity and 
frequency of cataplectic episodes. •  Inform client that cataplexy is not a fatal disease, 
choking on food and airway obstruction do 
not occur, and the pet is not suffering. 
• Inform client that activities such as 
hunting, swimming, and unleashed exercise 
put the patient at risk. •  If episodes are 
infrequent and quality of life is preserved, 
treatment should be postponed and 
environment adapted to avoid specific 
• Imipramine 0.5 mg/kg PO q8h. 
• Methylphenidate 0.25 mg/kg PO 
q12–24h. •  Selegiline 2 mg/kg PO q24h. 
• Yohimbine 50–100  μg/kg SC or PO 
q8–12h. •  Combination also possible—
imipramine and methylphenidate.
• Many patients develop drug tolerance; 
change of drug may become necessary. 
• Increased heart and respiratory rates, 
anorexia, tremors, exercise-induced 
  FOLLOW-UP
• Avoiding inciting activities may reduce 
episodes so that medication is not needed. 
• Patients with the inherited form may 
improve with age. •  Prognosis varies even 
with treatment; some patients remain 
De Lahunta A, Glass EN, Kent M. Veterinary 
pp. 491–496.
Author  Mylène-Kim Leclerc

Canine and Feline, Seventh Edition  955
N
Nasal and Nasopharyngeal Polyps
  BASICS
OVERVIEW
• Non-neoplastic, inflammatory growths 
arising from epithelium, usually originate 
from a stalk.
• Nasal—uncommon; originate from the 
mucosa of the nasal turbinates and are 
inflammatory in dogs and cats.
• Nasopharyngeal—relatively common; 
originate from the base of the epithelial lining 
of the tympanic bulla or eustachian tube; 
when polyps extend into the nasopharynx 
they are referred to as nasopharyngeal polyps; 
when extending into the ear, they are known 
as middle ear polyps, aural or auricular 
polyps, or benign, inflammatory polyps.
• Nasal polyps—middle-aged to older dogs 
and cats.
• Nasopharyngeal polyps—typically kittens 
and young adult cats, but can be seen in older 
cats (months—15 years), rarely seen in dogs.
SIGNS
Nasal Polyps
• Chronic mucopurulent nasal discharge.
• Noisy breathing—stertor.
• Nasal congestion and/or discharge.
• Sneezing or epistaxis.
• Decreased nasal airflow, generally unilateral.
• Generally nonresponsive to antibiotics.
Nasopharyngeal or Aural Polyps
• Inspiratory stridor.
• Gagging.
• Chronic otitis externa/otitis media.
• Head tilt.
• Ataxia.
Unknown—suspect congenital or response to 
chronic inflammatory processes.
  DIAGNOSIS
• Feline upper respiratory disease complex.
• Chronic otitis externa or media.
• Nasal or nasopharyngeal foreign body.
• Laryngeal paralysis.
• Nasal neoplasia—lymphoma, nasal 
adenocarcinoma.
• Laryngeal neoplasia—squamous cell 
carcinoma, lymphoma, adenocarcinoma.• Aural neoplasia—ceruminous 
N/A
Feline leukemia virus/feline immunodefi-
ciency virus (FeLV/FIV)—general retroviral 
screening.
IMAGING
• Skull radiographs—soft tissue density 
within nasal cavity, nasopharynx, tympanic 
bulla, external ear canal; 25% false-negative 
rate.
• CT and MRI—better sensitivity for nasal, 
nasopharyngeal, and aural masses.
• Digital palpation of soft palate, visual 
examination of the nasopharynx and larynx 
under general anesthesia utilizing spay hook, 
dental mirror, and laryngoscope.
• Flexible fiber-optic caudal rhinoscopy to 
examine the dorsal nasopharynx, choanae, 
and caudal nasal cavity.
• Rigid rostral rhinoscopy to examine the 
• Deep otoscopic examination.
• Fine-needle aspirate and/or biopsy.
• Cytology and histopathology.
  TREATMENT
• Excisional biopsy for nasal polyps.
• T raction removal of nasopharyngeal polyps 
via oral cavity.
• Ventral bulla osteotomy for nasopharyngeal 
polyps to release stalk and remove epithelial 
lining; may decrease rate of recurrence of 
polyps. Recommended if bullous involvement 
(clinical evidence of otitis media) is apparent.
• Consider anti-inflammatory course of 
corticosteroids following traction removal of 
nasopharyngeal polyps; decreased recurrence 
rate reported.
• Appropriate antimicrobial medications if 
secondary nasal or otic infection present.
  FOLLOW-UP
• Incomplete removal of polyp and stalk may 
result in recurrence.
• Horner’s syndrome can occur following 
removal by traction or ventral bulla 
osteotomy; usually transient but can be 
permanent.• Facial paresis or paralysis or vestibular 
syndrome may develop after bulla osteotomy 
but is generally transient.
• Prognosis excellent with complete removal.
• FeLV = feline leukemia.
Greci V, Mortellaro CM. Management of otic 
and nasopharyngeal, and nasal polyps in 
cats and dogs. Vet Clin North Am Small 
Anim Pract 2016, 46(4):643–561.
Holt DE, Goldschmidt MH. Nasal polyps in 
dogs: five cases (2005 to 2011). J Small 
Anim Pract 2011, 52(12):660–663.
Klose TC, MacPhail CM, Schultheiss PC, 
et al. Prevalence of select infectious agents 
in inflammatory aural and nasopharyngeal 
polyps from client-owned cats. J Feline Med 
Surg 2010, 12(10):769–774.
Reed N, Gunn-Moore D. Nasopharyngeal 
disease in cats: diagnostic investigation and 
specific conditions and their management. J 
Feline Med Surg 2012, 14(5):306–326.

956  Blackwell’s Five-Minute Veterinary Consult  
NNasal Dermatoses—Canine
  BASICS
Pathologic condition of the nasal skin 
involving either the haired portion (bridge 
of the nose/dorsal muzzle) or non-haired 
portion (nasal planum).
• Dogs <1 year of age—dermatophytosis, 
zinc-responsive dermatosis, dermatomyositis, 
demodicosis, eosinophilic folliculitis and 
furunculosis (often insect trigger; also seen in 
adult patients). • Zinc-responsive dermatosis—  
Siberian husky, Alaskan Malamute. 
• Dermatomyositis—collie, Shetland 
sheepdog. • Uveodermatologic syndrome—
Akita, Samoyed, Siberian husky. • Systemic 
lupus erythematosus (SLE) and discoid lupus 
erythematosus (DLE)—collie, Shetland 
sheepdog, German shepherd dog. • DLE may 
occur more often in females. 
• Epitheliotropic lymphoma—older dogs. 
• Dermal arteritis of the nasal philtrum—
Saint Bernard and other large breeds. • Nasal 
solar dermatosis—lightly pigmented breeds. 
• Nasal parakeratosis—Labrador retriever. 
• Senile idiopathic nasal hyperkeratosis—
cocker spaniel, Boston terrier, bulldogs. 
• Seasonal nasal hypopigmentation—
Labrador retriever, golden retriever, Siberian 
husky, Bernese mountain dog. • Idiopathic 
leukoderma/leukotrichia (vitiligo)—–
Doberman pinscher, Rottweiler, dachshund. 
• Reactive histiocytosis (“clown nose”)—
Bernese mountain dog, golden retriever. 
• Mucocutaneous pyoderma – German 
shepherd dog.
SIGNS
• Depigmentation. • Erythema. • Erosion/
ulceration. • Vesicles/pustules. • Crusts. 
• Scarring. • Alopecia. • Nodules/plaques. 
• Hyperkeratosis.
CAUSES
• Nasal pyoderma/furunculosis; mucocuta -
neous pyoderma. • Demodicosis. 
• Dermatophytosis, cryptococcosis , 
sporotrichosis, aspergillosis. • DLE and SLE. 
• Eosinophilic folliculitis and furunculosis. 
• Mosquito-bite hypersensitivity. 
• Pemphigus foliaceus (PF) and erythematosus 
(PE). • Pemphigus vulgaris (PV). • Nasal 
philtrum arteritis. • Nasal solar dermatitis. 
• Dermatomyositis. • Zinc-responsive 
dermatosis. • Uveodermatologic syndrome. 
• Superficial necrolytic dermatitis. • Vitiligo. 
• Idiopathic nasal depigmentation. • Contact dermatitis— irritant or hyper  sensitivity; 
plastic dish dermatitis, topical drug 
hypersensitivity (neomycin). • Neoplasia—
squamous cell carcinoma, basal cell 
carcinoma, epitheliotropic lymphoma, 
cutaneous histiocytosis. • T rauma. 
• Idiopathic sterile granuloma. • Idiopathic 
nasal hyperkeratosis. • Distemper virus 
dermatitis. • Xeromycteria – otitis media 
compromising sympathetic nerve supply/
parasympathetic function or lacrimal gland 
damaged, cause drying of nasal tissues.
• Adult cats—may be inapparent carriers of 
dermatophytes. • Rooting behavior—
pyoderma, dermatophytosis. • Sun exposure—  
nasal solar dermatitis, DLE, SLE, PE. 
• Poorly pigmented nose—nasal solar 
dermatitis, squamous cell carcinoma. • Large, 
rapidly growing breeds—zinc-responsive 
dermatosis. • Immunosuppression—
demodicosis, pyoderma, dermatophytosis. 
• Insect exposure—mosquito-bite dermatitis, 
eosinophilic folliculitis and furunculosis.
  DIAGNOSIS
• Lesions—confined to nose; precipitated by 
heavy sunlight exposure. • Begins in poorly 
pigmented skin at junction of nasal planum 
and dorsal muzzle. • Lightly pigmented 
eyelid margins may also be affected.
DLE
• Primarily affects nasal area. • May affect 
mucocutaneous margins of the lips and 
eyelids. • Exacerbated by sunlight. 
• Dermatitis often preceded by depig -
mentation. • Biopsy—interface dermatitis 
with pigmentary incontinence.
SLE
• Multisystemic disease. • Skin lesions—
often involve nose, face, mucocutaneous 
junctions; multifocal or generalized.
Pemphigus Foliaceus
• Lesions—usually start on face and ears; 
commonly involve footpads and pinnae; 
eventually generalize. • Biopsy—subcorneal 
pustules with acantholysis.
Pemphigus Erythematosus
ears; features of both PF and DLE; typically 
more severe than lesions of DLE. • Dermatitis 
often preceded by depigmentation. • Biopsy—
intraepidermal pustules with acantholysis and 
Demodicosis
• Often starts on face or forelimbs; affects 
only haired skin of the dorsal muzzle. • Juvenile-onset frequently facial at first. 
• May generalize.
Contact Dermatitis: Plastic (or Rubber) 
Dish Dermatitis
• Depigmentation and erythema of anterior 
nasal planum and lips. • No ulceration or 
crusting. • Uncommon; overly suspected—
lesions more often due to trauma from 
roughened bowl edges. Similar symptoms 
seen with trauma from rubber toys.
• Breeds at increased risk. • Young age of 
onset. • Nasal, facial, and extremity 
lesions—erosion, alopecia, scarring, and 
hyperpigmentation. • Lesions especially 
noted at points of trauma or pressure. 
• Polymyositis and megaesophagus may be 
seen. • Biopsy—interface dermatitis with 
follicular atrophy.
• Breeds at increased risk. • Dermatitis often 
preceded by ocular symptoms (uveitis). 
• Striking leukotrichia and leukoderma on 
nose, lips and eyelids. • Biopsy of early 
lesions—interface dermatitis, pigmentary 
Zinc-Responsive Dermatosis
• Breeds at increased risk. • Typical signal -
ment or diet (i.e., high-fiber or calcium 
supplementation). • Crusted lesions—face, 
mucocutaneous junctions, pressure points, 
footpads. • Biopsy—parakeratotic hyperkeratosis.
Eosinophilic Folliculitis and Furunculosis
• Rapid progression from popular papular/
nodular pattern to ulcers and plaques. 
• Highly pruritic. • Acute reaction to insect 
or arthropod bite and stings.
• Crusting and fissures on mucocutaneous 
junctions of lateral aspects of the nares, lips 
and perioral skin.
Mosquito Bite Hypersensitivity
• Seasonal pruritic dermatitis. • Erythema, 
papules, crusts affecting face and nasal 
planum, occasionally lesions on pinnae and 
feet. • Biopsy—eosinophilic inflammation, 
collagen necrosis around the hair follicles.
Other
• Dermatophytosis—haired portion of the 
nose; diagnosed by culture or biopsy. 
• Vitiligo—cutaneous macular depigmenta -
tion without inflammation on nose, lips, 
eyelids, footpads, and claws; leukotrichia 
with leukoderma may be seen; diagnosed by 
biopsy. • Nasal hypopigmentation—normal 
black coloration of nasal planum fades to 
light brown or whitish light pink color; loss 
of pigment is usually symmetrical and often 
becomes complete; in some individuals may 
be seasonal or wax and wane; considered 
cosmetic and not pathologic. • Idiopathic

Canine and Feline, Seventh Edition  957
N
nasal hyperkeratosis—dry, horny growths of 
keratin localized to nasal planum; may or 
may not be associated with digital hyper -
keratosis, possibly associated with senility. 
• Other diseases—differentiate by history or 
biopsy (i.e., neoplastic cell infiltrate).
• Usually normal. • SLE—may see hemolytic 
anemia, thrombocytopenia, evidence of 
glomerulonephritis (high BUN, proteinuria), 
joint disease, or other symptoms based on 
body system(s) affected.
• Skin scrapings— Demodex . • Cytology—
fungal organisms, bacteria, eosinophils 
(eosinophilic folliculitis and furunculosis), or 
acantholytic keratinocytes (pemphigus). 
• Dermatophyte test medium (fungal 
culture)—dermatophytosis. • Culture on 
Sabouraud agar—other fungal infections. 
• Bacterial culture and sensitivity or cytologic 
evaluation—pyoderma. • Joint tap—evidence 
of polyarthritis in SLE. • Antinuclear 
antibody (ANA)—positive in cases of SLE. 
• Ocular examination—uveitis in uveoderma -
tologic syndrome. • Electrocardiogram 
(ECG)—evidence of myocarditis in SLE. 
polymyositis in SLE and dermatomyositis. 
• Direct immunofluorescence—deposition of 
immunoglobulin at the basement membrane 
zone in DLE, SLE, and PE, and intercellular 
spaces of epidermis in PF , PE, and PV. 
• Neoplasia—cytology or biopsy.
• Folliculitis/furunculosis (± mites, bacteria, 
fungal elements)—demodicosis, dermatophy-
tosis, nasal pyoderma/furunculosis. 
• Eosinophilic predominance—mosquito-
bite dermatitis, eosinophilic folliculitis and 
furunculosis. • Follicular atrophy and 
perifollicular fibrosis—dermatomyositis. 
• Interface dermatitis—DLE, SLE, dermato-
myositis, uveodermatologic syndrome. 
• Intraepidermal pustules with acantholysis—
PF and PE. • Suprabasilar acantholysis—PV. 
• Parakeratotic hyperkeratosis—zinc-respon-
sive dermatosis. • Hypomelanosis—vitiligo, 
uveodermatologic syndrome. • Granulomatous/pyogranulomatous dermatitis—pyoderma, 
fungal, foreign body, idiopathic sterile 
granuloma. • Neoplastic cell infiltrate—  
cutaneous histiocytosis, other neoplasia.
  TREATMENT
• Outpatient, except SLE with multiorgan 
dysfunction or tumors requiring surgical 
excision or radiation therapy. • Reduce 
exposure to sunlight—DLE, SLE, PE, nasal 
solar dermatitis, squamous cell carcinoma. 
• Discourage rooting behavior—pyoderma, 
dermatophytosis. • Protection from insects 
(mosquito-bite dermatitis; eosinophilic 
folliculitis furunculosis). • Warm soaks—aid 
removal of exudate and crusts. • Replace 
plastic or rubber dish and avoid contact with 
topical drug or other agent causing 
• Fungal infections—systemic antifungals: 
ketoconazole, itraconazole; surgical excision 
of early discrete lesions (deep fungal 
infections). • Nasal solar dermatitis—topical 
corticosteroids; antibiotics for secondary 
infection; sunscreens; firocoxib. • DLE and 
PE—topical corticosteroids or tacrolimus 0.1% 
(Protopic); cyclosporine (Atopica); tetracycline 
and niacinamide; oral therapy (as for PF) if 
temporarily needed in severe cases. • PF , PV, 
SLE—immuno  suppressive therapy with 
prednisolone ± azathioprine (dogs), chlorambucil. 
• Vitiligo/nasal depigmentation—no 
treatment. • Neoplasia—surgical excision; 
chemotherapy; radiation therapy. • Idiopathic 
nasal hyperkeratosis—topical antibiotic-
corticosteroid cream, topical keratolytic and 
humectant; topical tacrolimus. • Other 
diseases—see specific cause.
Ketoconazole—caution in animals with 
liver disease or thrombocytopenia; avoid use 
in cats.  FOLLOW-UP
Varies with specific disease and treatment 
Ketoconazole may cause infertility in male 
dogs.
SYNONYMS
• Superficial necrolytic 
dermatitis = superficial necrolytic migratory 
erythema and hepatocutaneous syndrome. 
• Uveodermatologic syndrome = Vogt–
Koyanagi–Harada-like syndrome.
• ECG = electrocardiogram.
• PV = pemphigus vulgaris.
Harvey RG, Haar G. Ear, Nose and Throat 
Diseases of the Dog and Cat. Boca Raton, 
FL: CRC Press, 2017, pp. 225–288.
Five Minute Veterinary Consult: Clinical 
Companion; Small Animal Dermatology, 
2nd ed. Chichester: Wiley-Blackwell, 2011.
Resnick
available online(continued)  Nasal Dermatoses—Canine

958  Blackwell’s Five-Minute Veterinary Consult  
NNasal Discharge
  BASICS
May be serous, mucoid, mucopurulent, 
purulent, blood tinged, or frank blood 
(epistaxis); may contain food debris, from one 
or both nasal cavitiy(ies), may be permanent 
or in variable amount or consistency over 
time.
• Secretions—produced by mucous cells of 
the epithelium and submucosal glands; 
increased production from glandular 
hypertrophy and hyperplasia owing to 
irritation of the nasal mucosa by infectious, 
mechanical, chemical, or inflammatory 
stimuli. •  Blood from vascular leakage related 
to infectious, mechanical, chemical, 
inflammatory, or tumoral stimuli. 
• Xeromycteria—“dry nose”; facial nerve 
damage secondary to middle ear disease may 
decrease serous secretions from the lateral 
nasal glands leading to compensatory mucoid 
secretion; usually unilateral with unilateral 
nasal planum hyperkeratosis, ± 
keratoconjunctivitis sicca (KCS).
• Respiratory—mucosa of the upper tract, 
including the nasal cavities, sinuses, and 
nasopharynx; lower tract disease can also 
result in secretions from the upper airways. 
• Gastrointestinal—signs may be observed 
with swallowing disorders or esophageal or 
gastrointestinal diseases when secretions are 
forced into the nasopharynx. •  Hemic/
lymphatic/immune—blood-tinged discharge 
or epistaxis owing to platelet or hemostatic 
defects. •  Ophthalmic—may have KCS 
ipsilaterally if there is nerve damage due to 
middle ear disease.
• Dogs and cats. •  Young animals—cleft 
palate; nasal polyp, ciliary dyskinesia; 
immunoglobulin deficiency. •  Older 
animals—nasal tumors; primary dental 
disease (tooth root abscess). •  Hunting 
dogs—foreign body. •  Dolichocephalic 
dogs—aspergillosis, nasal neoplasia.
SIGNS
• Sneezing—often found concurrently. 
• Reverse sneezing—can be found 
concurrently, if nasopharyngeal involvement 
or passage of nasal secretions through the 
choanae towards the nasopharynx. 
• Important to know both the initial and 
current character of the discharge as well as 
whether it originally started unilaterally or 
bilaterally. •  Stertor—owners frequently 
report noisy breathing, especially when 
animal is sleeping. •  Response to previous antibiotic therapy common due to secondary 
• Secretions or dried discharge on the hair of 
the muzzle or forelimbs. •  May note 
reduction in nasal air flow, particularly with 
nasal neoplasia. •  Concurrent dental, 
nasopharyngeal, or lower airway disease. 
• Bony involvement—with a tumor or 
fourth premolar abscess; may be detected as 
facial or hard palate swelling or as pain 
secondary to fungal or bacterial osteomyelitis 
or neoplasia. •  Mucosal depigmentation of 
the nasal alar cartilage—observed with canine 
nasal aspergillosis. •  Mandibular lymphadeno -
megaly—neoplasia, fungal infection, dental 
disease. •  Polyp—may be visible on otoscopic 
exam, or pushing the soft palate down on oral 
exam. •  Chorioretinitis— 
may be seen with canine distemper or 
cryptococcosis. •  Eyeball deviation (abscess, 
sino-orbital aspergillosis in cats, tumors).
CAUSES
• Unilateral—often associated with non -
systemic processes; foreign body; dental-
related disease; fungal infections; nasal tumor; 
facial nerve damage leading to xeromycteria, 
nasopharyngeal stenosis, or atresia. 
• Bilateral—infectious agents (e.g., feline 
viral rhinotracheitis or calicivirus, canine 
herpesvirus, canine distemper, secondary 
bacterial infection); IgA deficiency; airborne 
irritant; allergy; ciliary dyskinesia; 
lymphoplasmacytic or hyperplastic rhinitis. 
• Unilateral progressing to bilateral—
Aspergillus ; nasal tumor. •  Either unilateral or 
bilateral—epistaxis; foreign body; extranasal 
disease; nasal parasites, inflammatory rhinitis. 
• Extranasal diseases—chronic pneumonia, 
chronic vomiting, nasopharyngeal diseases.
• Dental disease. •  Foreign bodies. 
• Infectious—poorly vaccinated animal; 
kennel situations, exposure to other animals. 
• Nasal aspergillosis. •  Thrombocyte 
disorder—thrombocytopenia or thrombo -
cytopathy: primary immune or secondary to 
infectious (i.e., rickettsial) disease or neoplasia. 
• Coagulation defect due to rodenticide 
intoxication. •  Nasal mites—kennel-raised 
dogs. •  Immunosuppression, chronic 
corticosteroid use; feline leukemia virus 
(FIV) infection. •  Chronic, low-grade 
pneumonia. •  Chronic vomiting. •  Chronic 
otitis (facial nerve damage).
  DIAGNOSIS
Important to differentiate nasal discharge, 
secretions, or crusting from diseases that occur at mucocutaneous junctions, such as 
pemphigus, vasculitis, or leishmaniosis.
Differential Diagnosis Causes
• Serous—mild irritation; viral and parasitic 
(e.g., nasal mites) disorders. •  Mucoid—
allergy; nonspecific airborne irritants; early 
neoplasia. •  Purulent (or mucopurulent)—
secondary bacterial or fungal infection, 
neoplasia. •  Serosanguinous to epistaxis—
nasal tumor and aspergillosis; after violent or 
paroxysmal sneezing episodes; coagulopathy, 
platelet disorder, angiostrongylosis and 
Results not specific for any particular cause 
but can detect concurrent problems; part of a 
thorough evaluation before general anesthesia 
for diagnostic procedures.
• Serologic tests—help to diagnose fungal or 
rickettsial disease. •  Coagulation studies—
determine platelet numbers and function, 
coagulation panel.
IMAGING
Skull Imaging
• Anesthetize and carefully position patient. 
• Perform before rhinoscopy and periodontal 
probing, which may cause nasal bleeding 
and alter imaging findings. •  Radiography 
(not performed when CT is available): 
◦ Lateral view—detect any periosteal 
reaction; note gross changes in the maxillary 
teeth, nasal cavity, and frontal sinuses; 
evaluate air column outlining the 
nasopharynx for filling defects. ◦ Open-
mouth ventrodorsal and intraoral views 
(using sheet film)—excellent for 
evaluating nasal cavities and turbinates. 
◦ Rostrocaudal view—evaluate each frontal 
sinus (periosteal reaction and filling). •  CT 
and MRI—CT superior to radiography in 
making diagnosis; CT and MRI help detect 
the extent of bony changes or CNS 
involvement associated with nasal tumors, 
fungal rhinitis, or chronic otitis.
May reveal areas of alveolar infiltrates in 
patient with chronic pneumonia, or situs 
inversus in some dogs with primary ciliary 
dyskinesia.
• Rhinoscopy—indicated with chronic or 
recurrent nasal discharge; acute epistaxis; 
evaluate both anterior and posterior; may be 
contraindicated with bleeding disorders. 
• Nasal cytologic examination—nonspecific 
inflammation most commonly found. 
• Fungal culture—difficult to interpret; false 
positives and negatives common. •  Bacterial 
culture may be useful when resistant 
organisms are suspected, but requires deep 
nasal sampling under anesthesia. •  Biopsy of

Canine and Feline, Seventh Edition  959
N
the nasal cavity—indicated with chronic nasal 
discharge or visualized abnormalities; multiple 
samples required to ensure adequate 
representation; may perform electron 
microscopy for suspected ciliary dyskinesia. 
• Bronchoscopy—indicated if there has been 
a history of coughing with nasal discharge. 
• Periodontal probing of all upper teeth—
perform after rhinoscopy; the normal gingival 
sulcus: dogs, ≤4 mm; cats, ≤1 mm. •  Blood 
pressure, platelets, and coagulation profile for 
epistaxis. •  Angiostrongylosis rapid detection 
test or PCR. •  Schirmer tear test, otoscopic 
exam, or CT—to evaluate for possible facial 
nerve damage from chronic otitis. •  T racheal/
bronchial scintigraphy and electron 
transmission microscopy—to confirm 
primary ciliary dyskinesia.
  TREATMENT
• Outpatient—adequate hydration, nutrition, 
warmth, and hygiene (keeping nares clean)— 
important with chronic sneezing and nasal 
discharge. Prioritize local therapy (nasal 
drops, nasal nebulization). •  Inpatient—any 
surgical treatment, topical therapy for 
• Secondary bacterial infection—antibiotics; 
choose a good Gram-positive spectrum of 
activity (e.g., amoxicillin, clavamox, clindamycin, 
azithromycin, cephalosporins). •  Attempt to 
dry up serous nasal secretions—decongestants 
(dogs: ephedrine at 10–50 mg total PO 
q8–12h, to a maximum of 4 mg/kg; cats: 
2–4 mg/kg q8–12h); topical vasoconstrictors 
(neosynephrine at 0.25–0.5% q8–24h or 
oxymetazoline at 0.25% q24h) but for a 
limited period of time—less than 1 week—
since they do not treat any cause and could 
induce damage to the nasal mucosa. 
• Dental-associated rhinitis—antibiotics; 
dental surgery as indicated. •  Foreign body—removal, antibiotics. •  Nasal 
parasites—ivermectin 300  μg/kg PO or SC 
weekly for 3 weeks or milbemycin 1 mg/kg 
PO weekly for 3 weeks (in collie and similar 
breeds) to treat Pneumonyssoides ; fenbendazole 
50 mg/kg PO q24h for 10 days to treat 
Eucoleus  (nasal nematode). •  Nonspecific 
inflammation—prednisolone 1–2 mg/kg PO 
q12–24h or piroxicam 0.3 mg/kg PO 
q24–48h. •  Canine nasal aspergillosis—topical 
treatment with enilconazole or clotrimazole. 
• Feline cryptococcosis or sporothricosis—
itraconazole 5–10 mg/kg PO q24h or 
fluconazole 50 mg/cat q12h. •  Feline 
aspergillosis—topical therapy, itraconazole. 
• Canine angiostrongylosis—antiparasitic 
(e.g., fenbendazole 50 mg/kg PO q24h for 3 
weeks), •  Neoplasia—radiotherapy and 
chemotherapy. •  Xeromycteria—oral 
administration of ophthalmic pilocarpine in 
attempt to stimulate nasal secretions.
• Ephedrine—in cardiac patients. 
• Ivermectin—in collies and similar breeds.
• Itraconazole—anorexia, nausea, vomiting, 
and high liver enzymes. •  Rebound 
phenomenon—reported with overuse of 
topical nasal vasoconstrictors.
  FOLLOW-UP
• Nasal discharge and sneezing—note 
changes in frequency, volume, and character. 
• Repeat rhinoscopy—indicated to ensure 
adequate response to treatment of fungal 
rhinitis. •  Recheck thoracic radiographs or 
bronchoscopy—monitor response to 
treatment for chronic pneumonia.
• Loss of appetite—especially in cats. 
• Extension of primary disease (e.g., fungal 
infection, tumor) into the mouth, eye, or 
brain. •  Respiratory distress—with nasal 
obstruction. •  Involvement of the 
cribriform plate in dogs with aspergillosis—CNS damage during topical drug therapy 
is a risk.
• Sinusitis. •  Dental disease. •  Secondary 
causes—coagulopathy, pneumonia, 
cricopharyngeal disease, megaesophagus.
Middle-aged to old patients—often associated 
with dental or neoplastic conditions.
N/A
The safety of most recommended drugs has 
not been established in pregnant animals.
SEE ALSO
• Nasal and Nasopharyngeal Polyps.
• Nasal tumor chapters.
• Nasopharyngeal Stenosis.
• Primary Ciliary Dyskinesia.
Cohn LA. Canine nasal disease: An update. 
Vet Clin North Am Small Anim Pract 
2020;50(2):359–374.
Lopez J. Sneezing and nasal discharge. In: 
Ettinger SJ, Feldmann EC, Cote E, eds., 
8th ed. Philadelphia, PA: Elsevier, 2017, 
pp. 111–115.
available online(continued)  Nasal Discharge

960  Blackwell’s Five-Minute Veterinary Consult  
NNasopharyngeal Stenosis
  BASICS
OVERVIEW
• Formation of a thin soft tissue membrane or a 
fibrous band of tissue at the choanae or 
anywhere above the soft palate, resulting in the 
occlusion of the caudal nasopharyngeal openings 
or narrowing of the orifice from a 1+ cm oval 
opening to a 1- to 2-mm opening or less.
• Inflammation secondary to chronic rhinitis, 
or from regurgitation or vomiting of material 
into the nasopharynx, particularly after 
anesthesia, should be considered as possible 
causes. Might also occur secondary to lodging 
of a foreign body in the choana.
• Congenital narrowing or dysgenesis of the 
region can also be encountered; thickened 
palatopharyngeal muscles have been reported 
as a cause of nasopharyngeal stenosis in the 
dachshund.
• Cats of any breed or sex.
• Less commonly seen in dogs.
• Age—any age as long as ample time has 
passed since exposure to the inciting cause; 
congenital cases may present early or late in life.
SIGNS
• Evidence of upper respiratory obstruction.
• Whistling, stridorous, or snoring sounds 
during respiration.
• Open-mouth breathing.
• Minimal nasal discharge in many cases.
• Duration of signs for at least several months.
• Aggravation of obstruction during eating 
or drinking.
• Failure to respond to antibiotics or 
• Absence of nasal airflow from one or both 
nares.
• Chronic upper respiratory disease.
• Foreign body or irritant contacting the 
affected area (perianesthetic regurgitation, 
reflux of gastric contents secondary to 
esophageal or gastric disease).
  DIAGNOSIS
• Nasopharyngeal polyps—seen during oral 
examination or by radiography or endoscopy.
• Chronic rhinitis or sinusitis—moderate to 
severe nasal discharge and sneezing; obvious 
radiographic changes in the rostral nasal 
cavity commonly seen.
• Foreign body—unilateral mucopurulent 
nasal discharge; radiographic abnormalities.
• Intranasal neoplasia—unilateral 
obstruction; nasal discharge often bloody; 
radiographic changes.• Mycotic rhinitis—moderate-to-severe nasal 
discharge, often hemorrhagic; radiographic 
changes.
• Laryngeal disease—no improvement with 
open-mouth breathing; lack of snoring or 
nasal discharge; abnormalities on laryngeal 
N/A
IMAGING
• Near-normal radiographic findings rostrally.
• Lateral neck radiograph will occasionally 
show a tissue obstruction.
• Nasopharyngeal stenosis sometimes can be 
visualized on CT. Sagittal reconstruction of 
the images can be required.
• Inability to pass a 3.5 French catheter 
through the ventral nasal meatus into the 
pharynx in a cat.
• Visualization of the stenosis by use of a 
retroflexed pediatric bronchoscope into the 
nasopharynx or use of an illuminated dental 
mirror.
  TREATMENT
• Balloon dilatation—noninvasive; fluoroscopy 
simplifies procedure; repeat episodes can be 
required (more often needed in the dog than cat).
• Stent placement can be required for cases 
with recurrent stenosis. Temporary red rubber 
stents have shown promise in reestablishing 
airway openings.
Antibiotics and steroids sometimes used post 
balloon dilation.
N/A
  FOLLOW-UP
Have owners evaluate nasal airflow at home 
and warn that recurrence is possible.
Berent AC, Kinns J, Weisse C. Balloon 
dilatation of nasopharyngeal stenosis in a 
dog. J Am Vet Med Assoc 2006, 
229:385–388.Glaus TM, Gerber B, Tomsa K, Keiser M. 
Reproducible and long-lasting success of 
balloon dilation of nasopharyngeal stenosis 
in cats. Vet Rec 2005, 157:257–259.
Unterer S, Kirberger RM, Steenkamp G, et al. 
Stenotic nasopharyngeal dysgenesis in the 
dachshund: Seven cases (2002–2004). J Am 
Anim Hosp Assoc 2006, 42:290–297.

Canine and Feline, Seventh Edition  961
N
Neck and Back Pain
  BASICS
Discomfort along the vertebral column.
Caused by multiple neurologic or non-
neurologic diseases (e.g., polyarthritis). 
Secondary to stimulation of nociceptors located 
in meninges, nerve roots, spinal nerves, vertebrae 
and associated structures (e.g., periosteum, joint 
capsules), and epaxial musculature. An intra  - 
cranial disease can develop referred neck pain 
when intracranial pressure is elevated.
• Nervous. •  Musculoskeletal. •  Neuromuscular.
Species
• Intervertebral disc herniation (IVDH)—dogs; 
extrusion chondrodystrophic breeds, protrusion 
large breeds. Less common in cats. •  Cervical 
spondylomyelopathy (CSM)—Doberman, Great 
Dane, Bernese mountain dog, Rottweiler, 
Dalmatian. •  Atlantoaxial (AA) instability—
small and miniature canine breeds (e.g., Yorkshire 
terrier, Chihuahua). •  Steroid-responsive 
meningitis-arteritis (SRMA)—Bernese mountain 
dog, Boxer, Beagle. •  Caudal occipital 
malformation syndrome and syringomyelia—
cavalier King Charles spaniel. •  Immune-
mediated polymyositis—Newfoundland, boxer.
• IVDH extrusion—unusual <2 years, peak 
3–8 years. •  IVDH protrusion—>5 years. 
• CSM—middle-aged to older Dobermans 
(mean: 6 years), young Great Danes (<3 
years). •  AA instability—young to middle-
aged. •  SRMA—<2 years (6–18 months). 
• Lumbosacral syndrome—middle-aged large 
dogs; German shepherd dogs.
SIGNS
Primary complaint—relates to perceived 
discomfort; e.g., vocalization, decreased activity, 
reluctance to get up or lie down, reluctance to 
go up or down stairs, inability to drink or eat 
from bowls on the floor (neck), neck muscle 
spasms. Neck pain may be intermittent.
• Abnormal neck carriage, reluctance to move 
the head, stiff neck posture. •  Arched back 
(kyphosis). •  Pain on spinal palpation and/or 
neck manipulation. •  Abdominal rigidity 
(referred from back pain). •  Increased epaxial 
muscle tone. •  Intermittent neck muscle spasms. 
• Reluctance to walk, stilted gait, limb stiffness, 
guarded short stride. •  Non-weight-bearing 
lameness (nerve root signature). •  Autonomic 
signs (e.g., tachycardia, pupillary dilation). 
• Neurologic deficits possible (e.g., paresis, 
ataxia). •  Pyrexia (SRMA, infectious diseases).CAUSES
• IVDH—most common cause of spinal pain 
in dogs. •  CSM. •  Spinal synovial cysts. 
• Vertebral facet hypertrophy. •  Calcinosis 
Anomalous/Developmental
• AA instability. •  Caudal occipital 
malformation syndrome (COMS) and 
syringomyelia. •  Vertebral malformations: 
e.g., hemivertebra (usually asymptomatic). 
• Osteochondromatosis. •  Dermoid sinus.
• Spinal (primary or secondary), nerve root–
peripheral nerve (e.g., peripheral nerve sheath 
tumor), muscle. •  Intracranial tumors with 
secondary increased intracranial pressure 
(ICP) (referred neck pain).
Feline hypervitaminosis A.
Inflammatory
• Discospondylitis, vertebral osteomyelitis, 
vertebral physitis. •  Infectious meningitis/
meningomyelitis—viral (e.g., feline infectious 
peritonitis [FIP]), bacterial, rickettsial, fungal, 
protozoal, parasitic, algae. •  Noninfectious 
meningitis/meningomyelitis—SRMA, 
meningoencephalomyelitis of unknown origin 
(MUO). •  Spinal epidural empyema. 
• Paraspinal abscess. •  Polyarthritis—immune-
mediated, infectious. •  Polymyositis—
immune-mediated polymyositis, infectious, 
exertional rhabdomyolysis.
Subarachnoid diverticulum (rarely painful).
Traumatic
• Spinal fracture, luxation. •  T raumatic 
Vascular
Spinal hemorrhage.
• Breed—chondrodystrophic (IVDH), 
miniature dog (AA instability). •  T rauma. 
• Previous surgical procedure (discospondylitis, 
subluxation). •  Malignant neoplasm. •  Bite 
wound, foreign body, urinary tract infection 
(UTI), endocarditis. •  Coagulopathy. •  Liver 
diet (hypervitaminosis A). •  Feline leukemia 
virus (FeLV) infection (spinal lymphoma).
  DIAGNOSIS
• Orthopedic disease. •  Abdominal pain 
(back). •  Behavioral or abnormal mentation 
(delirium). •  Increased ICP (referred neck 
pain). •  Nonpainful myelopathy—e.g., 
degenerative myelopathy, fibrocartilaginous 
embolic myelopathy. •  Paroxysmal disorders. 
• Feline hyperesthesia syndrome.CBC/BIOCHEMISTRY/URINALYSIS
• CBC usually normal. May see neutrophilia 
(SRMA, dyscospondylitis), thrombocytopenia 
(rickettsial disease, malignant neoplasm). 
• Elevated creatine kinase (CK), aspartate 
aminotransferase (AST)—myositis, recumbence, 
trauma, anorexia (cat). •  Hyperproteinemia—
neoplastic, infectious. •  UTI— primary focus 
for discospondylitis, with urinary retention. 
• Myoglobinuria—myositis.
• Serologic titers, PCRs (blood, CSF) for 
infectious diseases. •  Blood/urine cultures—
discospondylitis. •  IgA and acute phase 
proteins levels (blood, CSF) in SRMA. 
• Serum protein electrophoresis. 
• Coagulation panel.
IMAGING
Survey Spinal Radiography
• Not able to identify spinal cord 
compression. •  IVDH—may detect 
narrowed and/or mineralized intervertebral 
disc space. •  Detects discospondylitis but 
potentially normal first 3 weeks. •  Spinal 
neoplasms—osteolysis, bony proliferation, 
wider vertebral canal. •  Detects fractures, 
luxations, AA instability, vertebral facet 
hypertrophy, malformations, calcinosis 
circumscripta, osteochondromatosis.
Thoracic Radiography 
Detect neoplasms (primary or metastatic), 
disseminated infections, endocarditis, 
trauma-related lesions.
Detects and delineates spinal cord lesions as 
extradural, intradural–extramedullary and 
intramedullary. Low sensitivity in detecting 
parenchymal lesions.
CT
• More sensitive than radiographs for 
discospondylitis, vertebral fractures, bone 
tumors. Clearly defines bony lesions but less 
soft tissue contrast than MRI. Can be useful 
to diagnose IVDH extrusion if mineralized 
material. •  CT-myelogram—more sensitive 
to assess spinal cord compressive lesions.
MRI
More sensitive than CT for soft tissue. Most 
rewarding imaging technique for identifying 
location and extent of spinal cord parenchymal 
lesion, nerve roots, nerves, and muscle.
CSF
• Useful in meningitis/meningomyelitis, but 
normal or nonspecific in many other 
situations. Rarely, neoplastic cells can be 
detected (spinal lymphoma). •  Consider 
measuring IgA levels, acute phase proteins, 
serologic titers, PCRs, bacterial culture.
Arthrocentesis and Synovial Fluid 
Analysis
Polyarthritis

962  Blackwell’s Five-Minute Veterinary Consult  
NElectrodiagnostics
EMG, nerve conduction studies—detect and 
localize neuromuscular disease (e.g., 
polymyositis).
Fluoroscopy or CT-Guided 
Percutaneous Fine-Needle Aspiration 
(FNA)
Discospondylitis, neoplasms.
Biopsy
Bone (e.g., neoplasia, osteomyelitis), muscle 
(e.g., polymyositis).
  TREATMENT
• Inpatient—when severe clinical signs; 
emergency intensive care due to severe pain or 
neurologic deficit. •  Outpatient—when 
medical treatment is pursued (restricted 
exercise can be done). •  Emergency surgery—  
if traumatic spinal instability or severe 
neurologic deficit (nonambulatory paraparesis, 
tetraplegia) due to an acute spinal cord 
• Nonambulatory patients—soft bedding, 
alternate recumbence site, urinary bladder 
voiding. •  Vertebral instability—extreme care 
on manipulation to avoid exacerbating injury.
ACTIVITY
Restrict exercise at least 3–4 weeks in 
medically treated patients.
DIET
Change diet in case of hypervitaminosis A.
• Monitor pain, response to treatment and 
possible gait abnormalities. Relapses common 
in many diseases. •  Most common cause of 
spinal pain in dogs is IVDH. Inform that 
restricted activity and cage confinement for 
3–4 weeks are necessary when medical 
treatment is pursued; recurrence frequent. If 
pain persists or neurologic status deteriorates, 
surgical treatment is recommended, even as 
an emergency procedure.
Vary according to disease. Generally, deep 
pain perception is considered the most 
important prognostic indicator for functional 
recovery in neurologic disease. AA instability 
correction is associated with high perio -
perative morbidity and mortality.
• Opioids—morphine 0.1–1.0 mg/kg q4h 
(dog), hydromorphone 0.05–0.2 mg/kg q4h (dog), buprenorphine 0.005–0.02 mg/kg q8h 
(dog); SR 0.03–0.06 mg/kg q72h (dog), 
fentanyl (transdermal patch). •  Glucocorticoids—  
Use of glucocorticoids in acute spinal cord 
trauma is controversial as no benefits in 
outcome are proven. Medical management of 
acute IVDH should focus on cage 
confinement. Prednisone 0.5–1 mg/kg q24h 
(dog) in decreasing dosage could be used in 
many noninfectious chronic and compressive 
conditions (IVDH protrusion, CSM, etc.) but 
never in combination with nonsteroidal 
anti-inflammatory drugs (NSAIDs). Higher 
doses required in immune-mediated disease 
(2–4 mg/kg q24h). •  NSAIDs—potentially 
more effective in acute cervical IVDH. 
Meloxicam 0.1 mg/kg q24h (dog), carprofen 
2.2 mg/kg q12h (dog). •  Gabapentin 10–15 
mg/kg q8h PO (dog); chronic neuropathic pain 
(syringomyelia, nerve root disease). •  According 
to disease—antimicrobials (e.g., discospondylitis), 
immunosuppressive drugs, chemotherapy 
(neoplasms).
• Glucocorticoids, immunosuppressive 
agents—infections. •  Opioids—diarrhea 
caused by a toxic ingestion, constipation.
• Concurrent administration of NSAIDs and 
glucocorticoids is strongly contraindicated. 
• Glucocorticoids, NSAIDs—may cause 
gastrointestinal ulceration/hemorrhage. 
• Glucocorticoids—may cause UTI. 
• Vertebral instability or IVDH—strict cage 
rest mandatory while on anti-inflammatory 
and analgesic drugs; increased activity can 
exacerbate the problem. •  Opioids—caution 
if respiratory dysfunction, increased ICP , 
CNS depression, bradyarrhythmias. 
• Gabapentin—caution if renal insufficiency.
• Opioids—increased CNS and respiratory 
depression when combined with other CNS 
depressants. •  Gabapentin—oral antacids 
may decrease oral bioavailability 20%.
• NMDA antagonists (e.g., ketamine)—
analgesics. •  Pregabalin—chronic neuro -
pathic pain. •  Furosemide, omeprazol— 
COMS/syringomyelia. •  Azathioprine, 
cyclosporine, cytosine arabinoside—immune-
  FOLLOW-UP
• Primarily based on clinical signs and 
response to treatment. Initially, monitor at 
least once a week. If acute severe pain and/or 
neurologic deficit present, inpatient or daily 
monitoring recommended. Make adjustments or consider surgery when medical treatment 
is not effective. •  CSF analysis (e.g., SRMA), 
spinal radiographs (e.g., discospondylitis), 
acute phase proteins levels, bloodwork/
thoracic radiographs/ultrasound (e.g., 
neoplasms, infectious diseases).
Avoid excessive activity, jumping, going up-/
downstairs, and excess weight. Avoid neck 
collars (harness preferred).
• Recurrences or deterioration. Surgical 
treatment can be recommended on an 
emergency basis according to disease. 
• Chronic unresponsive pain. •  Permanent 
neurologic dysfunction. •  Spread to other 
locations, pathological vertebral fracture/
luxation (discospondylitis, neoplasms). 
• Degenerative joint disease (polyarthritis).
• Varies with disease, severity of clinical signs, 
and neurologic deficit. •  IVDH extrusion—
success with medical treatment in dogs with 
only pain or mild deficits is about 50%.
• Immune-mediated non-erosive polyarthritis 
and SRMA. •  Discospondylitis and UTI. 
• FeLV and feline spinal lymphoma. 
• Polymyositis and lymphoma. 
• Polymyopathies/myositis—megaesophagus/
dysphagia and aspiration pneumonia.
• AA = atlantoaxial. •  AST = aspartate 
aminotransferase. •  CK = creatine kinase. 
• COMS = caudal occipital malformation 
syndrome. •  CSM = cervical 
spondylomyelopathy (wobbler). •  EMG = 
electromyography. •  FeLV = feline leukemia 
virus. •  FIP = feline infectious peritonitis. 
• FNA = fine-needle aspiration. •  GME = 
granulomatous meningoencephalomyelitis. 
• ICP = intracranial pressure. •  IVDH = 
intervertebral disc herniation. •  MUO = 
meningoencephalomyelitis of unknown origin. 
drug. •  SR = slow release (drug formulation). 
• SRMA = steroid-responsive meningitis-
arteritis. •  UTI = urinary tract infection.
Dewey CW, da Costa RC. A Practical Guide to 
Canine and Feline Neurology, 3rd ed. Ames, 
IA: Wiley-Blackwell, 2016, pp. 329–436.
Platt S, Olby N. BSAVA Manual of Canine 
and Feline Neurology, 4th ed. Gloucester, 
UK: British Small Animal Veterinary 
Association, 2012.
Author  Luis GaiteroNeck and Back Pain  (continued)

Canine and Feline, Seventh Edition  963
NNecrotizing Encephalitis
  BASICS
OVERVIEW
• Historically restricted to a few breeds such 
as the pug, Yorkshire terrier, and Maltese 
dog. Described nowadays also in other 
breeds such as the Chihuahua, the shih tzu, 
and others. Even described in large-breed 
dogs. The disease includes necrotizing 
meningoencephalitis (NME) and necrotizing 
leukoencephalitis (NLE), since an overlap of 
clinical signs and histopathologic findings 
occurs.
• Systems affected—nervous.
• Genetics—a genetic basis (genetic risk 
loci) detected in pug dogs, Maltese dogs, 
and toy dog breeds; multifactorial disorder 
• Incidence/prevalence—not determined but 
disease occurring regularly.
• Geographic distribution—occurs worldwide, 
mostly seen in toy breeds.
Maltese, pugs, Yorkshire terriers, French 
bulldogs, Chihuahuas, shih tzus, Pekingese, 
and other toy breeds.
Mostly young adult dogs (range 4 months–10 
years).
SIGNS
Progressive signs related to a forebrain lesion 
(abnormal behavior, seizures, circling, 
blindness), brainstem lesions with central 
vestibular signs, or a multifocal lesion.
• Genetic risk factors.
• An infectious agent might be suspected, but 
was never confirmed; multifactorial disorder, 
  DIAGNOSIS
• Other CNS inflammatory/infectious 
diseases—differentiated on serology, CSF , 
MRI, and brain biopsy results.
• Neoplasia—differentiated on MRI findings 
and brain biopsy results.
Results are usually normal.
Genetic test for predisposition.IMAGING
MRI—results help support the clinical 
diagnosis considering breed, age, clinical 
signs, and course of the disease. Lesions may 
be asymmetric, multifocal prosencephalic 
with varying contrast enhancement, and can 
include multiple cystic areas of necrosis.
• CSF—pleocytosis with predominantly 
mononuclear cells; mild to marked protein 
• Brain biopsy—to confirm diagnosis.
• Necrosis and nonsuppurative inflammation 
of the cerebral gray and white matter; multi  - 
focal lesions; active lesions consist of a large 
malacic gliotic center surrounded by a wall of 
severe mononuclear inflammation.
• Old lesions consist of rarefied or cystic areas 
surrounded by intense astroglial sclerosis.
  TREATMENT
• Inpatient or outpatient based on the 
neurologic status.
• Symptomatic treatment recommended.
• Disease cannot be treated specifically; 
improvement with anti-inflammatory or 
• Seizures may be the only sign at onset of 
the disease in pug dogs; diagnostic workup 
including MRI in pug dogs presented with 
seizures is recommended.
• Symptomatic treatment.
• To control seizures, phenobarbital 2–6 mg/
kg PO q12h.
• Corticosteroids can reduce the inflammatory 
response and improve clinical signs (e.g., 
prednisolone or prednisone 1–2 mg/kg PO 
q24h for the first 1–2 weeks; then the dosage 
can be tapered slowly); frequently used 
medication: cytosine arabinoside 50 mg/m2 SQ 
q12h for 2-4 days, repeat about every 4 weeks 
(other dosage regimens possible); other 
immunosuppressive drugs are used successfully.
N/A
Procarbazine, azathioprine, cyclosporine, 
leflunomide, lomustine, mycophenolate 
mofetil.  FOLLOW-UP
• Regular clinical and neurologic 
examinations to monitor response to 
symptomatic treatment.
• Monitoring of seizures and phenobarbital 
serum levels.
N/A
• The course of the disease is chronic for 
months or even years; in every confirmed 
case, the neurologic signs have been 
• Prognosis is guarded, survival with good 
quality of life in part of the cases.
In one pug dog, myocardial necrosis was seen 
in addition to the encephalitic lesions.
N/A
Three pugs described in Japan had a history 
of pregnancy before onset of clinical signs.
Flegel T. Breed-specific magnetic resonance 
imaging characteristics of necrotizing 
encephalitis in dogs. Front Vet Sci 2017, 
864:203.
Hoon-Hanks LL, McGrath S, Tyler KL, et al. 
Metagenomic investigation of idiopathic 
meningoencephalomyelitis in dogs. J Vet 
Intern Med 2018, 32:324–330.
Schrauwen I, Barber RM, Schatzberg SJ, et al. 
Identification of novel genetic risk loci in 
Maltese dogs with necrotizing 
meningoencephalitis and evidence of a 
shared genetic risk across toy dog breeds. 
Plos ONE 2014, 9:e112755.
Author  Andrea Tipold

964  Blackwell’s Five-Minute Veterinary Consult  
NNeonatal Mortality and Canine Herpesvirus
  BASICS
• Death occurring between birth and 2–3 
weeks of age. • Fading syndrome describes a 
clinical presentation rather than a specific 
etiology.
• Four major factors lead to vulnerability of 
neonates—poorly developed thermoregulatory 
mechanisms; increased risk of dehydration 
(immature kidney function); increased risk of 
hypoglycemia (small reserve of glycogen); and 
immunologic immaturity (95% of antibodies 
from derived from colostrum). • Highly 
susceptible to environmental, infectious, 
nutritional, and metabolic factors.
All systems.
• Puppies and kittens. • Pedigree puppies, 
kittens—more prone to congenital and 
hereditary defects, higher overall incidence of 
stillbirth and neonatal mortality.
SIGNS
• Preweaning mortality —typically 10–30%; 
about 65% occur during first week; greater 
losses in a cattery or kennel should be 
considered abnormal. • Thorough history vital 
to identify potential causes; attention should be 
given to signalment, breeding history, 
vaccination, deworming history, exposure to 
toxins, problems during parturition, size of 
litter, feeding regimen, whelping environment, 
mothering abilities.
• Low birth weight, loss of weight, failure to 
gain weight. • Decreased activity, appetite. 
• Weakness. • Poor suckling response. 
• Constantly vocal or restless early, quiet and 
inactive later. • Separation from dam and rest 
of litter. • Low Apgar scores at birth (see 
Neonatal Resuscitation and Early Neonatal 
Care).
• Nonspecific. • Dark red or bluish ventral 
abdominal skin indicates sepsis or cyanosis. 
• Red to purple toes, swollen red and/or 
purulent umbilical stump may indicate sepsis. 
• Gross anatomic defects—e.g., cleft palate, 
imperforate anus, pectus excavatum, 
asymmetry of limbs; abnormal haircoat over 
dorsum may indicate spina bifida. 
• Weakness, hypothermia (newborn 
temperature is 34.7–37.2°C [94.5–99°F], 
rising to 36.1–37.8°C [99–100°F] during first 
week of life); hypoglycemia and dehydration 
are common interrelated findings. • Respiratory distress, diarrhea, 
CAUSES
Infection, poor maternal management, low 
birthweight and congenital abnormalities 
• Dam-related—dystocia or prolonged labor, 
cannibalism, lactation failure, trauma, 
inattention or overattention, inadequate 
nutrition (e.g., taurine deficiency in kittens). 
• Signalment—breed, older dam, larger litters 
associated with mortality rate. 
• Environmental—factors that discourage 
nursing and allow hypothermia including 
temperature or humidity extremes, inadequate 
sanitation, overcrowding, stress. • Nutritional—
inadequate, ineffective nursing, hypoglycemia, 
hypothermia-induced digestive dysfunction. 
• Neonatal isoerythrolysis—queen with 
blood type B, kitten with blood type A.
Birth Defects
• Gross anatomic defects—more frequent in 
kittens than puppies. • Alimentary—cleft 
palate, segmental intestinal agenesis/atresia, 
imperforate anus, congenital megaesophagus, 
portosystemic shunt, mucopolysaccharide 
storage disease. • Cardiac defects—valvular 
dysplasia, ventricular septal defect, atrio -
ventricular fistula, tetralogy of Fallot, patent 
ductus arteriosis, congenital rhythm 
disorders. • Respiratory defects—thoracic 
wall abnormalities, pectus excavatum, ciliary 
dyskinesia, surfactant deficiency. • Renal 
defects—agenesis, dysplasia, fanconi syndrome, 
polycystic kidney disease, ureteral 
abnormalities. • Endocrine—diabetes 
mellitus, hypothyroidism, hyposomatrotro -
pism, central diabetes insipidus. • CNS—
cerebellar hypoplasia and abiotrophy, 
hydrocephalus, spinal dysraphism, 
neuronopathies, lysosomal storage disease. 
• Hematologic—coagulopathies, von 
Willebrand disease, pyruvate kinase 
deficiency, hemolytic anemia, phosphofructo -
kinase deficiency. • Immune system—thymus 
dysfunction, atrophy. • Miscellaneous—
anasarca, skin or ocular defects.
• Viral: ◦ Kittens—feline calicivirus; feline 
leukemia virus (FeLV); feline immuno -
deficiency virus (FIV); feline herpesvirus type 
1, feline panleukopenia virus. ◦ Puppies—
canine adenovirus type 1; canine distemper 
virus; canine herpesvirus-1 (CHV-1); canine 
parvovirus type 1 (minute virus) and type 2; 
canine influenza virus, canine coronavirus. 
• Bacterial—acquired mainly across placenta 
or via umbilicus but also through 
gastrointestinal tract, respiratory tract, urinary 
tract, skin wounds: ◦ E. coli , β-hemolytic 
Streptococcus , coagulase-positive Staphylococcus , Salmonella  spp., Campylobacter  
spp., Bordetella bronchiseptica , Pasteurella 
multocida , Brucella canis , Leptospirosis . 
• Parasitic: ◦ Helminths— Toxocara  spp., 
Ancylostoma  spp. ◦ Protozoal— Toxoplasma , 
Neospora , Cryptosporidium , Giardia . 
◦ Coccidia— Isospora .
• Low birth weight, failure to gain weight; 
gain of 5–10% body weight per day 
acceptable: ◦ Kittens: minimum daily gain 
of 7–10 g. ◦ Puppies: should double in 
weight by 10–12 days. • Dystocia or 
prolonged labor. • Inbreeding—higher 
incidence of homozygous recessive 
genotype. • Blood type mismatch (cats). 
• Increased litter size, older dam, certain 
breeds. • CHV-1 is temperature sensitive; 
cold puppies more susceptible.
  DIAGNOSIS
Excessive losses often due to combination of 
environmental, immunologic, nutritional, 
infectious, and metabolic factors; detection 
and correction of all necessary to prevent 
ongoing losses.
CBC
• Hydration status and age influence results. 
(normal packed cell volume at 1 week 
33–52%, at 2 weeks 29–34%). • White 
blood cell concentration variable; thrombo -
cytopenia and neutrophilia (with left shift) 
if septic.
• Hypoglycemia. • Hypocholestrolemia, 
hypertriglyceridemia. • Low alkaline 
phosphatase activity, hypophosphatemia. 
• Low gamma-glutamyltransferase activity—
indicates failure to receive colostrum. • Other 
changes depend on organ system.
• Hemoglobinuria—with neonatal 
isoerythrolysis. • Bacteria—with infection. 
• Urine specific gravity >1.017 suggests 
inadequate hydration.
• FeLV/FIV tests. • Serology— Brucella canis ; 
CHV-1; canine influenza virus; Toxoplasma ; 
Neospora ; Leptospirosis .
IMAGING
• Abdominal ultrasound. • Thoracic and 
abdominal radiographs can show aspiration 
pneumonia, gastrointestinal obstruction, but 
difficult to obtain diagnostic films (low contrast).

Canine and Feline, Seventh Edition  965
NDIAGNOSTIC PROCEDURES
• Histopathologic—tissues collected at 
necropsy. • Metabolic urine screening—rule 
out inborn errors of metabolism. • Virus 
isolation. • Bacterial culture. • PCR of 
placenta or fetal tissues— Brucella canis ; 
CHV-1; Toxoplasma ; Neospora ; Leptospirosis . 
• Blood typing in cats (dam and kitten). 
• Post-mortem—important; examine as soon 
after death as possible to minimize autolysis: 
◦ Stomach—empty: lack of nursing; consider 
dam-related causes or neonatal problems; 
filled with milk: suggests sudden death or 
digestive dysfunction. ◦ Thymus small—not 
necessarily thymic dysfunction; atrophy can 
be a result of multiple causes (e.g., viral 
infection, stress, toxins, nutrition, defective 
immune system). ◦ Petechiation—common; 
suggests coagulopathy or septicemia. ◦ Urine 
in urinary bladder—implies renal dysfunction 
or inadequate care by dam. ◦ Lungs—
homogeneous dark red color typical of a 
stillborn animal that has not taken a breath; 
hemorrhage, edema, congestion, mottled 
color abnormal but nonspecific. ◦ CHV-1—
renal hemorrhage, multifocal areas of necrosis 
in lungs and liver are pathognomonic 
findings. • Note malformations. • Multiple 
tissue samples—submit to diagnostic 
laboratory; virus isolation, bacterial culture 
and sensitivity, PCR, histopathology; check 
with laboratory for proper submission.
  TREATMENT
• Correct deficiencies in husbandry or breeding 
selection. • Warmth—slowly warm neonate to 
36–37.2°C (97–99°F) by 1°C per hour, if 
necessary; provide ambient temperature of 
29–35°C (85–95°F) and relative humidity of 
55%–65%. • Oxygen—supplement at 
30–40%, if necessary. (Difficult to detect 
hypoxia as puppies and kittens do not always 
hyperventilate; clinical signs can include 
increased respiratory effort, bradycardia, 
hypotension, distended abdomen due to 
aerophagia.) • Fluid therapy—IV via jugular or 
cephalic vein; intraosseous in femur or humerus. 
• Fluid requirements: 80–100 mL/kg/day, or 
3-6 mL/kg/h using balanced isotonic replacement crystalloid; volume overload can 
occur due to immature kidney function 
• Dextrose supplementation—0.5–1.0 g/kg IV/
IO, given as a bolus, diluted to 5% dextrose in 
isotonic replacement crystalloid; then 
administered as CRI (2.5–5% dextrose in 
crystalloids) as needed. • Do not attempt to feed 
if body temperature <35°C (95°F) and no 
sucking reflex; once warmed, encourage nursing. 
• Neonatal isoerythrolysis—prevent nursing for 
first 24 hours after birth; provide alternative 
colostrum, strip dam’s colostrum before allowing 
kittens to nurse. • CHV-1—prevention is key; 
antiviral medication has not proven effective; 
CHV-1 vaccine available in Europe.
• Antibiotics—penicillins (penicillin G, 
ampicillin, amoxicillin, amoxicillin with 
clavulanic acid) and first-generation 
cephalosporins preferred; reduce adult dose 
by one-half and use same dosage interval. 
• Supplement—milk replacer; serum or 
plasma can be provided (10–20 mL/kg PO, 
split in 2–4 feedings in first 24 hours of life) 
as colostrum supplement. • Vitamin K1 
0.01–0.1 mg SC or IM, once.
Aminoglycosides, tetracyclines, 
fluoroquinolones, trimethoprim/sulfonamide, 
chloramphenicol—avoid during neonatal 
period.
Drug absorption, distribution, metabolism, 
and excretion during first 5 weeks of life 
differs from adults.
N/A
N/A
  FOLLOW-UP
• Hydration—monitor regularly (mucous 
membranes, urine specific gravity, nursing 
and urination). • Body weight—monitor daily or every other day. • Dam—monitor 
mothering abilities and milk production; 
supplement nutrition to neonates if required.
N/A
Some infectious agents have zoonotic 
potential (e.g., Toxoplasma , Leptospira , 
Brucella ).
Do not breed individuals with congenital 
defects.
SYNONYMS
• Fading puppy or kitten syndrome. 
• Wasting syndrome.
• CHV-1 = canine herpesvirus-1.
vetmed/article/articleDetail.jsp?id=197161
 Suggested Reading:
Davidson AP . Canine herpesvirus infection. 
In: Sykes JE, ed., Canine and Feline 
Saunders, 2014, pp. 166–169.
stillbirth and neonatal death in dogs and 
2012, 42:501–513.
Tonneessen R, Sverdrup Borge K, et al. 
Canine perinatal mortality: a cohort study 
of 224 breeds. Theriogenology 2012, 
77:1788–1801.
Wilborn RR. Small animal neonatal health. 
Vet Clin North Am Small Anim Pract 2018, 
48:683–699.
Hannah N. Pipe-Martin. 
available online(continued)  Neonatal Mortality and Canine Herpesvirus

966  Blackwell’s Five-Minute Veterinary Consult  
NNeonatal Resuscitation and Early Neonatal Care
  BASICS
The neonatal period is defined as the first 3 
weeks of extrauterine life. It is a delicate period 
where neonates are particularly susceptible to 
disease as well as congenital pathology. 
Neonatal organ systems including renal and 
hepatic function, gastrointestinal disease, and 
basic reflexes such as gagging, shivering, and 
thermoregulation are undeveloped or absent. 
Efforts to assist the neonate with cardio­
pulmonary function and consciousness during 
the immediate period following birth is 
referred to as neonatal resuscitation.
Young puppies and kittens less than 3 weeks 
of age.
SIGNS
• Poor weight gain (<5–10% of body weight 
per day) is the earliest sign of failure to thrive.
• Hypothermia (normal body temperature 
for 1st week of life is 35–36°C [95–97°F]).
• Hypovolemia (concentrated urine, dry or 
tacky mucous membranes).
• Bradycardia (normal 200–250 bpm at 
birth, 180–200 bpm until 2 weeks).
• Excessive crying.
• Weak or absent suckle reflex.
• Prolonged stage 2 labor >5 hours.
• Decreased Apgar score within 8 hours of 
life (6 or lower on a 10 ­point scale; see 
Table 1).
• Low birth weight (less than 50% of average 
litter weight).
• Agalactia.
• Failure of passive transfer.
• Improper hygiene.
• Bacterial or viral infections.
  DIAGNOSIS
• Congenital defects.
• Bacterial sepsis.
• Alkaline phosphatase and gamma ­
glutamyltransferase enzyme activities—
markedly elevated in neonates that have 
ingested colostrum.
• Urine—color is best indication of hydration 
status; should be nearly colorless in healthy 
neonate; brown color may indicate hemoglobinuria in kittens with neonatal 
N/A
IMAGING
Thoracic radiography—helpful in diagnosis 
of aspiration pneumonia, a common cause of 
neonatal mortality.
• Congenital abnormalities such as cleft 
palate, atresia ani, omphalocele, anasarca, etc. 
may be noted at the time of birth. Many 
breeders will opt for euthanasia in these 
instances.
• Renal petechiation may indicate herpesvirus 
• On necropsy, clotted milk in the stomach 
often indicates intestinal ileus secondary to 
hypothermia. Only saliva in the stomach may 
indicate death secondary to starvation and 
failure of the bitch to produce milk.
• If possible, submit both deceased neonate 
and placenta for necropsy.
  TREATMENT
• Vigorous external rubbing with a warm dry 
towel is sufficient for neonatal resuscitation at 
birth. Suction may be warranted to clear 
secretions from airway. “Swinging” neonates 
to clear airways is contraindicated and may 
result in cerebral hemorrhage.
• Cyanotic or pale mucous membranes at 
birth necessitate oxygen administration or 
mouth ­to­mouth resuscitation.
• Bradycardia during the first 4 days is not 
vagally mediated and is indicative of 
• Warm slowly if body temperature is below 
34.5°C (94°F). External heat sources are best, 
or warmed interosseous or IV fluids may be 
used.
• Do not feed unless body temperature is 
greater than 34.5°C (94°F) due to presence of 
intestinal ileus.
• Milk should be given in the form of 
commercially available milk replacer. 
Homemade formula and goat’s milk are 
deficient in arginine and may result in 
cataract formation.
• Only feed neonates via a bottle if they are 
warm and have a strong suckle reflex. As 
neonates cannot gag during the first week of 
life, it is the author’s preference that all 
neonates be fed via orogastric intubation until 
strong enough to nurse due to the risk of 
aspiration pneumonia. Droppers, cosmetic 
sponges, and syringe feeding are not 
recommended feeding methods due to 
excessive swallowing of air and high risk of 
aspiration.• IV or intraosseous fluids are treatment of 
choice for hypovolemia. Neonates poorly 
absorb SQ fluids due to lack of fat. All fluids 
should be warmed before administration to 
avoid hypothermia.
Neonatal Resuscitation Drugs
• Epinephrine 0.2 mg/kg IV, in umbilical 
vein or intraosseous route if cardiac arrest.
• Naloxone 0.1 mg/kg IM, only if opioids 
used during anesthesia of bitch.
• Doxapram—unlikely to be beneficial due 
to lack of efficacy in stimulating hypoxic 
neonates.
Antibiotics for Neonatal Sepsis
• Ceftiofur sodium (Naxcel) 2.5 mg/kg SQ 
q12h.
• Amoxicillin/clavulanic Acid (Clavamox) 
13.75 mg/kg PO q12h.
Plasma or Serum for Failure of Passive 
Transfer
• Live donor can be used or commercially ­
available fresh frozen plasma at body 
• For puppies: 22 mL/kg divided and administered 
SQ. Half dose can be administered PO if 
neonate is less than 12 hours old.
• For kittens: 15 mL per kitten, SQ, in 5 mL 
boluses given at birth, at 12 hours, and 24 
hours of age.
Pain Control
• Opioids (fentanyl, buprenorphine) may be 
used with careful monitoring.
• Fluoroquinolones may be used safely in 
neonates until 3 weeks of age. Afterwards 
there is a risk of cartilage defects with use.
• Tetracyclines (doxycycline), aminoglycocides 
(amikacin), and chloramphenicol should not 
be used unless absolutely necessary due to 
systemic effects.
• Metronidazole is contraindicated in patients 
younger than 2 weeks of age.
• Atropine is contraindicated during neonatal 
resuscitation due to exacerbation of myocardial 
should not be used in neonates due to 
potential for renal injury.
  FOLLOW-UP
Weight gain should be monitored daily at 
home using a scale capable of measuring

Canine and Feline, Seventh Edition  967
Ngrams or ounces (kitchen scale). Failure to 
gain weight is the first clinical sign of a 
problem and should not be ignored.
• Neonates should be kept separate from 
other animals for the first 3 weeks postpartum 
to avoid disease transmission.
• Good environmental hygiene is 
imperative.
• Environmental temperatures should be kept 
warm yet comfortable (19.5–24°/67–75°F) 
and free of drafts in order to prevent the dam 
from leaving the whelping box. Increased 
temperatures of 27–32°C (80–90°F) are only 
required if puppies are orphaned.
• Ensure colostrum ingestion during the first 
12 hours of life. If dam is not producing 
milk, or neonate is orphaned, serum or 
plasma should be given to provide immunoglobulins, but colostrum should be 
the first line of defense.
• Ensure the umbilicus is clamped and 
cleaned with a tincture of iodine solution 
immediately following birth to prevent 
ascending umbilical infections.
• Dam’s mammary glands should be 
inspected daily for cleanliness and early signs 
of mastitis. Neonatal septicemia has been 
reported to occur secondary to bacterial 
exposure via the dam’s milk.
• Probiotics can be given to minimize 
diarrhea associated with antibiotic use. Pastes 
and powders can be mixed into milk replacer 
or dabbed under the tongue to provide dosage 
without a risk of aspiration.
Highest mortality rate occurs within the first 
7 days of life (17–30% in dogs).EXPECTED COURSE AND PROGNOSIS
• Depends on underlying cause—many 
“fading puppies/kittens” can be saved with 
early recognition and intervention.
• Bacterial sepsis and herpesvirus infections 
in puppies have fair to poor prognosis.
Authors  Erin E. Runcan and Tessa Fiamengo
Consulting Editor  Erin E. RuncanApgar scoring: each row is scored based on newborn activity and scores added together to obtain full Apgar score.  
A score of 7–10 indicates no distress, 4–6 indicates moderate distress, and 0–3 severe distress. Scoring should be performed  
at 5 minutes, 30 minutes, and 2 hours after birth. 
0 1 2 Score:
Mucous membrane color Cyanotic Pale Pink
Heart rate <180 bpm 180–220 bpm >220 bpm
Respiratory effort/rate No crying/<6 rpm Mild crying/6–15 rpm Crying/>15 rpm
Reflex irritability Absent Feeble reaction (grimace) Vigorous reaction (grimace/vocalization)
Mobility, muscle tone Flaccid Some tone in extremities Active movements
Suckling (scored as −, +, ++)
Rooting (scored as −, +, ++)
Source: From Wilborn (2018). Reprinted with permission of Elsevier.(continued)  Neonatal Resuscitation and Early Neonatal Care
Table 1

968  Blackwell’s Five-Minute Veterinary Consult  
NNeonicotinoid Toxicosis
  BASICS
OVERVIEW
• Neonicotinoids are a class of insecticides 
referred to as nitroguanidines, neonicotinyl, 
chloronicotines, and most recently as 
chloronicotinyls. Neonicotinoids are 
chemically similar to nicotine.
• Like nicotine, neonicotinoid insecticides act 
as agonists to nicotinic acetylcholine receptors.
• They act on insects at three different 
postsynaptic nicotinic receptors found in CNS.
• Wide safety margin in mammals due to 
high selectivity for specific subtypes of 
nicotinic receptors in insects.
• Compounds used in veterinary products 
include imidacloprid, nitenpyram and 
dinotefuran. Other common neonicotinoid 
products on the parket include acetamiprid, 
clothianidin, nithiazine, sulfoxaflor, and 
thiamethoxam.
• Widespread use in veterinary medicine for 
flea control. Used as oral tablets and in collars 
and topical spot on products.
• Used in termite and grub control and crop 
production against sucking and chewing pests 
in a variety of formulationsas well as ant and 
roach baits.
• Primarily dogs—chewing up ant bait 
containers, collars, boxes of tablets, bags, 
liquid products.
• Rarely reported in cats.
SIGNS
• Imidacloprid has low toxicity in mammals. 
Results of a chronic feeding study revealed no 
adverse effects in dogs given imidacloprid at a 
dose of 15 mg/kg/day for a year. Topical 
application in dogs and cats at a dose of 50 
mg/kg also caused no adverse effects.
• Most common adverse effects observed 
were decreased activity, tremors, mydriasis or 
miosis and uncoordinated gait; hypothermia 
was observed at higher doses.
• Alopecia and erythema have been reported 
following dermal application.
• Due to the large safety margin of safety 
margin in mammals, CNS signs are rarely seen.
• Oral toxicity is possible if the concentration 
or dose is excessively high.
• Dietary indiscretion in dogs increases risk 
of exposure.
products.
  DIAGNOSIS
History of exposure and clinical signs.  TREATMENT
• Dermal exposure—bathe with liquid 
• Oral exposure—dilute with cool water, 
emesis, gastric lavage, activated charcoal, 
depending on amount ingested, time of 
ingestion, and clinical signs.
• Baseline CBC, chemistry profile, and urinalysis 
to rule out any preexisting organ dysfunction, 
which could increase the risk for toxicosis.
• Antihistamines and/or dexamethasone SP 
for signs of dermal hypersensitivity.
• IV or SC fluids (crystalloid) as needed for 
• Dog emesis—apomorphine 0.04 mg/kg IV.
• Cat emesis—dexmedetomidine 7 mcg/kg 
IM or IV; or xylazine 0.44 mg/kg IM or SC. 
Avoid hydrogen peroxide due to risk for 
hemorrhagic gastroenteritis.
• Activated charcoal with a cathartic 
(sorbitol), 1 g/kg × one dose.
• Methocarbamol 50–220 mg/kg IV. Max daily 
dose 330 mg/kg/day (cats and dogs). Give 1/2 
dose rapidly, wait until animal relaxes, and give 
remainder of dose to effect.
• Diphenhydramine (dog and cat): 2–4 mg/kg 
IM, PO q8–12 hours; 0.5–2 mg/kg IM, IV, SC. 
• Dexamethasone sodium phosphate: 0.5 mg/kg 
IV (dog); 0.125–0.5 mg per cat IM or IV.
  FOLLOW-UP
Patients usually recover with symptomatic 
and supportive care; no long-term organ 
damage is expected.
N/A
and more likely to chew up product containers.
detoxification capabilities.
N/A
Studies confirmed that imidacloprid is not 
mutagenic, non-embryotoxic, and 
nonteratogenic.INTERNET RESOURCES
• Extension Toxicology Network, Imidacloprid, 
Cornell PMEP: http://pmep.cce.cornell.edu/
profiles/extoxnet/haloxyfop-methylparathion/
imidacloprid-ext.html
• National Pesticide Information Center, 
Imidacloprid fact sheet: http://npic.orst.edu/
factsheets/imidagen.html
• Wismer T, Small Animal Toxicosis, 
Insecticides, VSPN: http://www.vspn.org/
Library/misc/VSPN_M01289.htm
Dryden MW, Ectoparasiticides used in small 
animals. Neonicotinoids.  In: Merck 
Veterinary Manual, revised 2015
Ensley SM. Neonicotinoids. In: Gupta RC, 
ed., Veterinary Toxicology Basic and 
Elsevier, 2012, pp. 596–598.
Hovda LR, Hooser SB. Toxicology of new 
pesticides for use in dogs and cats. Vet 
Clinics of North America, Small Animal 
Practice 32:455–467, 2002.

Canine and Feline, Seventh Edition  969
NNeosporosis
  BASICS
OVERVIEW
• Neospora caninum —obligate, intracellular, 
coccidial, protozoan.
• Domestic and wild canids excrete infective 
oocysts in feces; numerous ruminant 
intermediate hosts.
• T ransmission—vertical (transplacental or 
transmammary), ingestion of sporulated 
oocysts in dog feces, or ingestion of infected 
tissues from intermediate hosts.
• Disease caused by necrosis and 
inflammation from cyst rupture and 
tachyzoite invasion.
• Neurologic disease in dogs; other organ 
systems less commonly affected.
• Dogs—puppies and adults.
• Cats—experimentally infected; antibodies 
in domestic and wild cats without known 
disease; N. caninum  myocarditis reported in 
adult lion.
SIGNS
• Young dogs (4 weeks to 6 months of 
age)—ascending lower motor neuron 
paralysis, myositis, muscle atrophy, fibrous 
muscle contracture, and arthrogryposis; may 
progress to tetraparesis/plegia, trismus, 
dysphagia, hypoventilation; subclinical disease 
of other organ systems possible; less common: 
meningoencephalomyelitis, hepatitis, 
myocarditis, pneumonia, acute dyspnea, 
• Adult dogs—meningoencephalomyelitis 
and/or polymyositis; lesions can be found 
anywhere in CNS but have predilection for 
the cerebellum, resulting in slowly progressive 
cerebellar ataxia ± other cerebellovestibular 
signs; uncommonly affects other organs.
• Nodular dermatitis, particularly in 
immunosuppressed dogs.
Raw meat may be a risk factor; should be 
avoided.
  DIAGNOSIS
Other infectious disease (toxoplasmosis, 
sarcocystosis, hepatozoonosis, mycoses, rabies, 
canine distemper), neuronal storage diseases, 
noninfectious meningoencephalomyelitis or 
polymyositis, or immune-mediated 
neuromuscular disease, neoplasia.
• Dependent on the organ system involved.• Muscle involvement—creatine phospho -
kinase and aspartate aminotransferase 
activities increased.
• CSF analysis—normal to markedly increased 
total nucleated cell count; mononuclear 
pleocytosis more common than neutrophilic or 
eosinophilic; elevated total protein.
• Serologic testing (IFA, ELISA, and 
immunoprecipitation)—CSF or serum.
• Antibodies do not crossreact with 
Toxoplasma gondii , but do with Neospora 
hughesi , an equine protozoan.
• Organism detection—oocysts in feces; must 
distinguish from Hammondia  spp.
• Tachyzoites in aspirates, smears, or biopsies 
need to be differentiated from those of 
Toxoplasma  (immunohistochemistry).
• PCR—diagnostic tool, distinguishes 
between other parasites.
IMAGING
MRI of adult dogs—moderate to marked 
cerebellar atrophy with or without meningeal 
contrast enhancement; single or multifocal 
T2-weighted hyperintensities that contrast 
enhance within the CNS or muscles.
Muscle biopsy in dogs with myositis can 
identify organism by microscopy or PCR.
• Nonsuppurative encephalomyelitis.
• Severe nonsuppurative inflammation of 
cerebellar leptomeninges and cortex (more 
severe than that caused by T. gondii ); 
cerebellar atrophy.
• Myositis, myofibrosis.
• Polyradiculoneuritis.
• Pneumonia, cerebellar atrophy, multifocal 
necrotizing myocarditis, and nodular 
dermatitis possible.
• Ulcerative and pyogranulomatous 
• Histology—differentiate by location in host 
cell cytoplasm ( T. gondii  within a parasito-
phorous vacuole).
• Tissue cysts—those of N. caninum  have 
thicker walls; differentiated from T. gondii  by 
• Electron microscopy—rhoptries of N. 
caninum  tachyzoites electron dense; those of 
T. gondii  honeycomb.
  TREATMENT
• Long treatment period (min. 8 weeks); 
continue treatment 2 weeks beyond plateau 
of clinical improvement.
• Consider treatment of all puppies with 
infected littermates.
• Avoid immunosuppression if possible.  MEDICATIONS
• Ideal treatment unknown; clindamycin 
most commonly used but bradyzoites persist 
despite treatment.
• Clindamycin 10–20 mg/kg PO q12h.
• T rimethoprim-sulfadiazine (TMS) 15 mg/
kg PO q12h.
• Combination therapy—clindamycin and 
TMS, clindamycin and pyrimethamine 
(1 mg/kg PO q24h), or TMS and 
N/A
  FOLLOW-UP
• Progression of clinical disease might cease 
• Once muscle contracture or ascending 
paralysis has occurred, prognosis for clinical 
improvement is poor.
• Serologically test dam or other in-contact 
dogs and cattle.
N/A
SEE ALSO
Toxoplasmosis
Dubey JP , Lappin MR. Toxoplasmosis and 
neosporosis. In: Greene CE, ed., Infectious 
Louis, MO: Saunders Elsevier, 2012, pp. 
806–827.
Silva RC, Machado GP . Canine neosporosis: 
perspectives on pathogenesis and 
management. Vet Med 2016, 7:59–70.
Author  Renee Barber

970  Blackwell’s Five-Minute Veterinary Consult  
NNephrolithiasis
  BASICS
• Nephroliths—uroliths located in the 
renal pelvis or collecting diverticula of 
the kidney.
• Nephroliths or nephrolith fragments may 
pass into the ureters (ureteroliths).
• Nephroliths that are not infected, causing 
obstruction or clinical signs, or progressively 
enlarging are termed incidental  nephroliths.
Nephroliths can obstruct the renal pelvis or 
ureter, predispose to pyelonephritis, and lead 
to compressive injury of the renal parenchyma 
and chronic kidney disease (CKD); see 
urolithiasis chapters for pathophysiology.
• Renal/urologic—affects the urinary tract, with 
potential for obstruction, recurrent urinary tract 
infection (UTI), or progressive CKD.
• Obstruction of the renal pelvis or ureter 
with pyelonephritis may result in septicemia 
and affect any body system.
GENETICS
See specific chapter on type of stone.
• Nephroliths comprise 1–1.5% of uroliths 
submitted to the Minnesota Urolith Center 
for analysis. The true incidence of nephroliths 
is likely higher. Many animals with nephro­
liths are asymptomatic, or are not treated by 
methods that allow retrieval of uroliths for 
analysis.
• Composition of canine nephroliths 
submitted for analysis, in descending 
frequency: calcium oxalate, struvite, 
compound, purines, calcium phosphate, 
cystine, and silica. Composition of nephro­
liths in cats (descending frequency): calcium 
oxalate, dried solidified blood calculi, 
compound, struvite, calcium phosphate, and 
purine.
Species
Dogs
• Calcium oxalate—shih tzu, Yorkshire 
terrier, bichon frise, miniature schnauzer, and 
Maltese.
• Struvite—miniature schnauzer, shih tzu, 
pug, and miniature poodle.
• Purine—English bulldog, Dalmatian, 
Yorkshire terrier, and shih tzu.
• Cystine—Newfoundland, English bulldog, 
and French bulldog.Cats
Domestic shorthair, European and American 
shorthair, domestic longhair, Persian, Siamese 
and Scottish fold.
• Dogs—mean age 10 years (range 2 
months–21.5 years).
• Cats—mean age 7.7 years (range 5 
months–19.5 years).
• Dogs—nephroliths slightly more common 
in females than males; struvite nephroliths, 
females > males; however, calcium oxalate, 
cystine, and urate nephroliths males > females.
• Cat— nephroliths slightly more common 
in females than males; for calcium oxalate 
females > males; however, noncrystalline 
matrix (includes dried blood), and urate 
nephroliths males > females.
SIGNS
Many patients are asymptomatic, and the 
nephroliths are diagnosed during evaluation 
of other problems.
• None or hematuria, vomiting, and recurrent 
UTI; dysuria and pollakiuria in animals with 
UTI or concomitant urocystoliths.
• Uremia in animals with bilateral obstruction 
or nonfunctional contralateral kidney.
• Signs referable to lower urinary tract 
urolithiasis if uroliths are present in the upper 
and lower urinary tract.
• Renal colic with acute abdominal/lumbar 
pain and vomiting is possible.
Abdominal or lumbar pain upon palpation of 
kidneys or no significant findings.
CAUSES
See chapters on each urolithiasis. 
Oversaturation of the urine with calculogenic 
minerals is a risk factor for urolithiasis.
• Alkaluria—struvite and calcium phosphate 
uroliths.
• Aciduria—calcium oxalate, cystine, urate, 
and xanthine uroliths.
• Urine retention and formation of highly 
concentrated urine.
• Lower UTI—ascending infection and 
• Conditions that predispose to UTI.
  DIAGNOSIS
• Consider nephroliths in any patient with 
CKD, recurrent UTI, acute vomiting (pancreatitis, gastroenteritis, intestinal or 
gastric obstruction, etc.), or abdominal or 
lumbar pain (e.g., intervertebral disc 
protrusion, peritonitis).
• Nephroliths are usually confirmed by 
radiographs or ultrasonography; differentiate 
mineralization of the renal pelvis or collecting 
diverticula from true nephrolithiasis.
• CBC—usually normal; patients with 
pyelonephritis may have leukocytosis, 
immature neutrophilia, and thrombocytopenia.
• Serum biochemistry—usually normal 
unless bilateral obstruction, pyelonephritis, or 
compressive renal injury leads to acute kidney 
injury (AKI) or CKD; hypercalcemia may 
contribute to formation of calcium oxalate or 
calcium phosphate nephroliths.
• Urinalysis—may reveal hematuria and 
crystalluria; crystal type may suggest mineral 
composition; pyuria, proteinuria, and 
bacteriuria may also be seen with UTI.
• Submit nephroliths or nephrolith fragments 
for quantitative analysis.
• Urine culture may confirm UTI or 
concurrent pyelonephritis.
IMAGING
• Can detect radiopaque nephroliths (e.g., 
calcium phosphate, calcium oxalate, struvite) 
by survey radiography; cystine and silica are 
slightly radiopaque.
• Purines (urate or xanthine) are often 
radiolucent or faintly radiopaque when large 
unless they contain other radiodense minerals.
• Use ultrasonography or contrast CT to 
confirm, size and number of nephroliths or 
ureteroliths.
After extracorporeal shock wave lithotripsy 
(ESWL), fragments can be retrieved for 
quantitative analysis by voiding, cystoscopic 
basket retrieval, or voiding 
urohydropropulsion.
  TREATMENT
Manage patients with incidental nephro­
liths as outpatients. When appropriate, 
medical dissolution protocols can be 
administered to outpatients. Removal of 
nephroliths by surgery or ESWL requires 
DIET
Medical dissolution of nephroliths requires a 
diet appropriate for the specific nephrolith 
type. See Medications.

Canine and Feline, Seventh Edition  971
NCLIENT EDUCATION
• Incidental nephroliths—may not require 
removal but should be monitored periodically 
by urinalysis, urine culture, and radiography. 
Nephroliths may cause obstruction at any 
time, which can result in hydronephrosis 
without clinical signs. Conservative manage­
ment and monitoring carries a risk of 
undetected and potentially irreversible renal 
damage, which must be weighed against the 
potential renal damage from nephrotomy.
• Nephroliths often recur after removal; 
monitor the patient every 3–6 months.
• Indications for removal of canine 
nephroliths—obstruction, recurrent infection, 
progressive nephrolith enlargement, and a 
nonfunctional contralateral kidney. In cats, 
only obstructive uroliths in the renal pelvis or 
ureters are treated (see Ureterolithiasis).
• T reatment options for nephroliths—
medical dissolution, surgery, and ESWL. 
Calcium oxalate is the most common 
nephrolith in dogs and cats, and is not 
amenable to medical dissolution. Medical 
dissolution of nephroliths causing outflow 
obstruction requires endoscopic or surgical 
placement of a ureteral stent.
• Surgical options—nephrotomy, percutaneous 
endoscopic nephrolithotomy, or surgically 
assisted endoscopic nephrolithotomy. 
Endoscopic nephrolithotomy may be preferred 
over ESWL for nephroliths >1.5 cm in diameter.
• ESWL—safe and effective method of treating 
canine nephroliths and ureteroliths; nephrolith 
fragments pass down the ureter into the bladder 
and are voided with urine or removed by 
voiding urohydropropulsion. Large (1–1.5 cm) 
nephroliths may be managed by endoscopic 
placement of ureteral stent to induce ureteral 
dilatation followed by ESWL 2–4 weeks later.
• ESWL is not effective for treatment of 
nephroureteroliths in cats.
• Antibiotics selected on the basis of urine 
culture and sensitivity testing as needed; 
periprocedural antibiotics are recommended 
when infected nephroliths are treated by 
ESWL or surgical removal.
• Medical dissolution protocols are limited to 
struvite, purine, and cystine uroliths.
• When feasible, consumption of water in high 
moisture (canned) foods should be incorporated 
into dissolution protocol. Target urine specific 
gravity <1.020 (dogs), <1.025 (cats).• Medical dissolution protocols for canine 
struvite nephroliths include struvite ­preventative 
or ­dissolution diets and culture ­guided 
antibiotic therapy for the duration of 
dissolution.
• Medical dissolution of canine purine 
nephroliths can be attempted by a purine ­
restricted diet, allopurinol 15 mg/kg PO 
q12h, and supplemental potassium citrate as 
needed to maintain urine pH ~7.0.
• Medical dissolution of canine cystine 
nephrolithiasis can be attempted using a 
therapeutic diet, 2 ­mercaptopropionylglycine 
(2­MPG, tiopronin) 15 mg/kg PO q12h, and 
supplemental potassium citrate as needed to 
maintain urine pH ~7.5.
• Do not use allopurinol without dietary 
purine restriction; this combination may 
cause xanthine nephrolithiasis in dogs 
predisposed to urate urolithiasis.
• Do not give acidifying diets to azotemic 
patients unless blood pH and total CO2 are 
monitored for development of metabolic 
acidosis.
  FOLLOW-UP
Abdominal radiographs or ultrasonography, 
urinalysis, and urine culture every 3–6 
months to detect nephrolith recurrence. Dogs 
treated with ESWL—check every 2–4 weeks 
by radiographs and ultrasonography until 
nephrolith fragments have passed.
Eliminate factors predisposing to individual 
urolith type, augment urine volume, and 
correct factors contributing to urine 
retention. Dietary therapy is indicated for 
prevention of calcium oxalate, urate and 
cystine nephroliths. Castration of male dogs 
with cystine uroliths aids in prevention.
Hydronephrosis, AKI, CKD, recurrent UTI, 
• Highly variable; depends on nephrolith 
type, location, and size, secondary compli­
cations (e.g., obstruction, infection, CKD), 
and owner compliance with treatment and 
prevention protocol.
• Incidental nephroliths may remain inactive 
for years, resulting in an excellent prognosis.
• Return to normal health and good 
prognosis have been observed with ESWL for 
treatment of dogs with nephroliths.• The prognosis for patients with CKD 
caused by nephrolithiasis depends on the 
severity and rate of progression of CKD.
• Nephroliths causing outflow obstruction 
should not be dissolved medically without 
Hyperadrenocorticism and glucocorticoid 
administration are associated with calcium 
oxalate uroliths, and UTI resulting in struvite 
ESWL is contraindicated in pregnant animals.
SYNONYMS
• Kidney stones.
• Nephroureteroliths
• Renal calculi.
• Renoliths.
• Kidney calculi.
SEE ALSO
• Urolithiasis, specific types.
• 2­MPG = 2 ­mercaptopropionylglycine.
• ESWL = extracorporeal shock wave 
lithotripsy.
Adams LG, Goldman CK. Extracorporeal 
shock wave lithotripsy. In: Polzin DJ, 
Bartges JB, eds. Nephrology and Urology of 
Small Animals. Ames, IA: Blackwell 
Publishing, 2011, pp. 340–348.
Berent AC, Adams LG. Interventional 
management of complicated nephrolithiasis. 
In: Weisse CW, Berent AC, eds., Veterinary 
Imaging ­Guided Interventions. Ames, IA: 
Wiley ­Blackwell, 2015, pp. 289–300.
Author  Larry G. Adams
acknowledge the prior contributions of Carl 
A. Osborne, Jody P . Lulich, and Lori A. 
Koehler. 
available online(continued)  Nephrolithiasis

972  Blackwell’s Five-Minute Veterinary Consult  
NNephrotic Syndrome
  BASICS
Concurrent proteinuria, hypoalbuminemia, 
hypercholesterolemia, and third-space fluid 
accumulation (i.e., ascites, subcutaneous 
edema, etc.). Partial nephrotic syndrome 
refers to proteinuria, hypoalbuminemia, 
hypercholesterolemia without fluid 
• Magnitude of hypoalbuminemia and 
proteinuria causing nephrotic syndrome in 
dogs and cats is unknown; although affected 
patients usually have very low serum albumin 
concentrations, not all hypoalbuminemic 
patients will develop nephrotic syndrome.
• Reduced plasma oncotic pressure may result 
in hyperaldosteronism, which induces sodium 
and water retention, leading to edema and 
ascites. • Hypercholesterolemia is a 
consequence of decreased catabolism and 
increased hepatic synthesis of lipoproteins. 
• Complications include hypertension, 
hypercoagulability, muscle wasting, and 
weight loss. • Thromboembolism is a 
consequence of a generalized procoagulative 
state, due to increased platelet number and 
sensitivity, urinary loss of antithrombin, and 
increased concentrations of clotting factors.
• Renal/urologic—persistent proteinuria. 
With progressive disease and nephron loss, 
azotemia chronic kidney disease and uremia 
may occur. • Cardiovascular—edema, ascites, 
hypercholesterolemia/hyperlipidemia, 
hypertension, hypercoagulability, and 
thromboembolic disease.
GENETICS
Familial glomerular diseases have been 
reported (see Glomerulonephritis and 
Amyloidosis), but may be less likely to result in 
nephrotic syndrome than nonfamilial disease.
• Nephrotic syndrome is an uncommon 
complication of glomerular disease, with a 
median of 0.5 new cases per year diagnosed at 
8 veterinary teaching hospitals. • Nephrotic 
syndrome has not been associated with 
histologic subtype of glomerular disease. 
Amyloidosis and immune-complex mediated 
glomerulonephritis have the highest 
magnitude of proteinuria and might be 
expected to have a higher prevalence of 
Species
Dogs with nephrotic syndrome are typically 
younger than those with non-nephrotic 
glomerular disease (mean, 6.2 years vs. 8.4 
years).
None
SIGNS
• Pitting subcutaneous edema and/or ascites. 
• Clinical signs associated with an underlying 
infectious, inflammatory, or neoplastic disease 
may be the primary reason for seeking 
veterinary care. • Rarely, acute dyspnea, 
severe panting, weakness, or collapse due to 
pleural or pericardial effusion, pulmonary 
edema, or pulmonary thromboembolism.
• Dependent pitting, subcutaneous edema, or 
ascites. • Complications of hypertension: 
retinal hemorrhage or detachment, papilledema, 
arrhythmia and/or murmur secondary to left 
ventricular hypertrophy. • Dyspnea and/or 
cyanosis with pleural effusion or pulmonary 
CAUSES
• Glomerular disease may be a consequence of 
chronic inflammatory conditions (e.g., infection, 
neoplasia, or immune-mediated diseases). 
• Nephrotic syndrome is unlikely to be solely a 
consequence of severe proteinuria; additional 
unidentified factors appear to be necessary.
  DIAGNOSIS
Proteinuria
• Rule out inflammatory or hemorrhagic 
postglomerular urinary tract disease (e.g., 
bacterial cystitis/pyelonephritis, urolithiasis, 
tubular renal failure, or lower urinary tract 
neoplasia). Inflammation of the urinary tract 
is usually associated with active urine 
sediment. • Protein-losing nephropathies 
typically associated with inactive urine 
sediment (although hyaline casts may be 
present); renal biopsy is the only accurate way 
to distinguish the various types of glomerular 
disease.
Hypoalbuminemia
Rule out decreased albumin production 
(severe liver disease) and gastrointestinal 
albumin loss (protein-losing enteropathy).
• Persistent, significant proteinuria with 
inactive urine sediment. • Hypoalbuminemia 
and hypercholesterolemia. • Renal failure may occur with advanced disease. Azotemia 
may precede loss of urine concentrating 
ability.
Urine protein:creatinine ratio (UPC)—
confirms and quantifies the severity of 
proteinuria and can be used to assess response 
to therapy or progression of disease.
IMAGING
• Radiography—loss of abdominal detail due 
to ascites, pleural effusion (uncommon), 
pulmonary edema, or pericardial effusion 
(very uncommon) may be present. 
• Abdominal ultrasonography—confirms 
peritoneal and retroperitoneal fluid. Mild 
renomegaly may be observed with glomerular 
diseases.
Renal biopsy is indicated if significant and 
persistent proteinuria with inactive urine 
sediment exists. Microscopic evaluation of 
renal tissue will establish subtype of 
glomerular disease and help in formulating a 
prognosis. Consider renal biopsy after CBC, 
serum biochemistry profile, urinalysis, UPC, 
and coagulation testing are completed.
Renal biopsy specimens should be evaluated by 
light, fluorescent, and electron microscopy by a 
pathologist with expertise in nephropathology. 
Some of the more common glomerular 
diseases include glomerulonephritis (e.g., 
immune-complex mediated, membranous, 
membranoproliferative, proliferative), minimal 
change disease, hereditary nephritis, amyloidosis, 
podocyopathy, focal segmental glomeruloscle-
rosis, glomerulosclerosis.
  TREATMENT
• Most can be treated as outpatient. 
• Severely azotemic or hypertensive patients, 
or those with thromboembolic disease may 
require hospitalization.
• Abdominocentesis—reserve for patients 
with respiratory distress or abdominal 
discomfort caused by ascites. Excessive fluid 
removal will promote fluid accumulation 
and electrolyte abnormalities. • Plasma 
transfusion is not indicated for treatment of 
hypoalbuminemia. Very large volumes of 
plasma are required to significantly increase 
serum albumin concentration, and 
transfused proteins have short half-lives. 
• IV albumin can be used in patients with 
life-threatening complications due to fluid 
accumulation (e.g., pulmonary edema; 
pleural effusion). • Hypotonic 
“maintenance”-type fluids (e.g., 0.45%

Canine and Feline, Seventh Edition  973
NNaCl) as IV fluid therapy may minimize 
extravascular fluid accumulation. • Synthetic 
colloids may exacerbate fluid extravasation 
in patients with nephrotic syndrome. These 
fluids should therefore be limited to patients 
with immediate, life-threatening needs for 
oncotic pressure support.
ACTIVITY
Activity restriction may increase likelihood of 
thromboembolic disease; activity promotes 
fluid mobilization and lymphatic uptake.
DIET
• Sodium-reduced, high-quality, low-quantity 
protein diets are recommended, such as 
prescription “renal diets.” • Normal or high 
dietary protein may contribute to renal 
disease progression by exacerbating 
glomerular hyperfiltration, proteinuria, and 
glomerulosclerosis. However, dogs that have 
persistent and severe hypoalbuminemia may 
benefit from amino acid supplementation.
• Identifying and correcting underlying 
disease may slow or stop the progression of 
kidney disease. • Renal biopsy is required to 
differentiate between the various subtypes of 
glomerular disease and to optimize treatment 
protocols. • Nephrotic syndrome is associated 
with shortened survival time. In one canine 
study, median survival time of nephrotic 
syndrome was 12.5 (range 0–2,783 days), vs. 
104.5 (range 0–3,124 days) with non-
nephrotic glomerular disease. Azotemia and 
uremia are associated with shorter survival.
Animals with severe hypoalbuminemia (i.e., 
<2 g/dL) present unique challenges to 
anesthesia. Consideration should be given to 
referral of these patients to a secondary or 
tertiary care facility if anesthesia and/or 
surgery are indicated.
See Glomerulonephritis.
Edema and Ascites
• Dietary sodium reduction. • Reserve 
abdominocentesis and diuretics for patients 
discomfort. Overzealous diuretic use may 
result in dehydration and acute renal 
decompensation. • Severe, persistent 
extravascular fluid accumulation should be 
treated with an aldosterone antagonist 
(spironolactone 1–2 mg/kg PO q12h), and low doses of loop diuretics (i.e., furosemide 
0.5–2 mg/kg PO q8–12h). • Plasma or 
albumin transfusions provide only temporary 
benefit.
• Angiotensin receptor blocker (ARB) (e.g., 
telmisartan 1 mg/kg PO q24h) or an 
inhibitor (e.g., enalapril 0.5 mg/kg PO q12h) 
decrease severity of proteinuria. Because 
proteinuria is toxic to renal tubules, therapy 
should be initiated at the time of diagnosis, 
unless severe azotemia is present. • Aspirin 
(1–5 mg/kg PO q24h) or clopidogrel (1.1 
mg/kg PO q24h) decreases thromboembolism 
risk.
Highly protein bound drugs may be 
contraindicated if their margin of safety is 
small.
• Dose adjustment may be needed for highly 
protein-bound drugs that have a wider 
margin of safety. • Use ACE inhibitors or 
ARBs cautiously in patients with serum 
creatinine >5.0 mg/dL. • Diuretics should be 
used cautiously in nephrotic syndrome 
because of the risk of causing or worsening 
azotemia.
See Precautions.
  FOLLOW-UP
UPC; serum urea nitrogen, creatinine, 
albumin, and electrolyte concentrations; 
blood pressure; and body weight. Nephrotic 
syndrome is a dynamic condition and affected 
animals may require frequent reevaluation to 
address new symptoms or evaluate changes in 
N/A
• See Glomerulonephritis for complications 
unassociated with nephrotic syndrome. 
• Complications more likely to develop 
include: thrombosis (e.g., pulmonary 
thromboembolism), electrolyte disturbances, 
particularly with repeated abdominocenteses 
or high doses of diuretics.
Nephrotic syndrome is associated with a 
faster progression to azotemia and uremia, 
and decreased median survival time when compared to dogs that have glomerular 
disease without nephrotic syndrome.
• Amyloidosis. • Glomerulonephritis. 
• Glomerulopathy. • Hypercoagulability. 
Familial glomerular diseases should be 
considered in young animals with nephrotic 
syndrome.
Glomerular diseases can occur with some 
zoonotic infectious diseases.
Likely high risk in those patients with severe 
hypoalbuminemia and/or hypertension.
SYNONYMS
N/A
SEE ALSO
• ARB = angiotensin receptor blocker. 
• UPC = urine protein:creatinine ratio.
Atlas of Renal Lesions in Proteinuric Dogs: 
https://ohiostate.pressbooks.pub/
vetrenalpathatlas/
Brown S, Elliot J, Francey T, et al. Consensus 
recommendations for standard therapy of 
glomerular disease in dogs. J Vet Intern 
Med 2013, 27(Suppl.1):S27–S43.
Klosterman ES, Moore GE, de Brito Galvao JF , 
et al. Comparison of signalment, 
clinicopathologic findings, histologic diagnosis, 
and prognosis in dogs with glomerular disease 
with or without nephrotic syndrome. J Vet 
Intern Med 2011, 25:206–214.
Author  Shelly Vaden
M. Pressler. 
available online(continued)  Nephrotic Syndrome

974  Blackwell’s Five-Minute Veterinary Consult  
NNephrotoxicity, Drug-Induced
  BASICS
Renal injury caused by a pharmacologic 
agent used to diagnose or treat a medical 
disorder.
• Drugs can cause nephrotoxicosis by 
interfering with renal blood flow, glomerular 
function, tubular function, or inducing 
interstitial inflammation.
• Many drugs are nephrotoxic because they 
are excreted primarily by the kidneys.
• Most nephrotoxic drugs cause proximal 
renal tubular necrosis.
• If renal injury is severe, acute kidney injury 
develops.
• Gastrointestinal—inappetence, vomiting, 
diarrhea, or melena due to gastrointestinal 
irritation or uremic ulceration.
• Endocrine/metabolic—metabolic acidosis 
due to decreased elimination of acid by 
kidneys and inability to reclaim bicarbonate 
filtered into tubules by glomeruli.
• Hemic/lymphatic/immune—anemia due to 
blood loss or decreased red blood cell survival 
in patients with uremia; increased suscepti­
bility to infections because of immune 
dysfunction in patients with uremia.
• Nervous—depression, lethargy associated 
with effect of uremic toxins on the CNS.
• Neuromuscular—weakness due to systemic 
effects of uremia.
• Respiratory—tachypnea or respiratory 
distress due to uremic pneumonitis or 
compensatory response for metabolic acidosis.
Species
N/A
Any age; older patients are more susceptible.
N/A
SIGNS
• Polyuria and polydipsia; sometimes 
oliguria.
• Oral ulcers.
• Uremic halitosis.CAUSES
• Aminoglycosides—all drugs in this class are 
potentially nephrotoxic, including neomycin, 
gentamicin, amikacin, kanamycin, and 
streptomycin. Due to frequent use in the past, 
nephrotoxicosis associated with aminoglycoside 
treatment was most often associated with 
gentamicin.
• Tetracyclines—outdated products can cause 
acquired Fanconi ­like syndrome characterized by 
glucosuria, proteinuria, and renal tubular acidosis; 
IV administration to dogs at high dosages ( >30 
mg/kg) can cause acute kidney injury.
• Administration of sulfa drugs (e.g., 
trimethoprim–sulfadiazine) has been 
associated with acute kidney injury in dogs, 
but no causal relationship has been proven.
Antifungal Drugs
Amphotericin B.
Antineoplastic Drugs
• Cisplatin—clinically important cause of 
nephrotoxicosis in dogs.
• Doxorubicin—possible cause of nephro­
toxicosis in cats but not well documented.
(NSAIDs)
• Aspirin, ibuprofen, naproxen, carprofen, 
piroxicam, meloxicam, flunixin meglumine, 
and others may cause nephrotoxicosis.
• Most likely to cause renal injury in patients 
with preexisting kidney disease or patients 
with concomitant dehydration or other causes 
of hypovolemia.
• Enalapril, benazepril, and others.
• Most likely to cause acute kidney injury in 
patients with hyponatremia, dehydration, or 
Radiographic Contrast Agents
IV administration of ionic radiographic 
contrast agents can cause acute kidney injury, 
especially in patients with dehydration, 
hypovolemia, or hypotension associated with 
inhalational anesthesia.
• Advanced age, probably because older 
patients have preexisting kidney disease.
• Kidney disease, inactive or active.
• Renal hypoperfusion; potential causes include 
any disorder associated with hypovolemia (e.g., 
vomiting, hemorrhage, hypoadrenocorticism), 
low cardiac output (e.g., congestive heart failure, 
pericardial disease, cardiac arrhythmias, 
inhalational anesthesia), or renal vasocon­
striction (e.g., NSAID administration).
• Electrolyte and acid–base abnormalities 
including hypokalemia, hyponatremia, 
hypocalcemia, hypomagnesemia, and 
metabolic acidosis.• Concurrent drug therapy—administration 
of furosemide increases nephrotoxicosis of 
aminoglycosides; treatment with cytotoxic 
drugs (e.g., cyclophosphamide) may increase 
nephrotoxic potential of drugs.
• Fever.
• Sepsis.
  DIAGNOSIS
acute kidney injury (e.g., ethylene glycol 
toxicosis, raisin/grape ingestion [dogs], lily 
toxicosis [cats], renal ischemia, lepto  ­ 
spirosis).
• Most patients have a history of recent 
treatment (i.e., within the previous 2 weeks) 
with a potentially nephrotoxic drug; acute 
kidney injury may occur several days after 
discontinuation of an aminoglycoside.
• Accidental ingestion of large doses of 
medications may occur, especially with 
palatable chewable formulations (prescribed 
for this patient or other animals).
• Determine all drugs that have been 
administered to the patient, including 
over­the­counter preparations (e.g., aspirin, 
ibuprofen, and naproxen) and medications 
prescribed for human use (e.g., NSAID or 
ACE inhibitor).
• Hemogram—usually normal unless 
concomitant problems exist (e.g., gastro­
intestinal hemorrhage associated with 
administration of NSAIDs).
• Biochemistry—normal in early stages of 
drug­induced nephrotoxicosis or reveals signs 
consistent with acute kidney injury including 
azotemia, hyperphosphatemia, and metabolic 
acidosis.
• Urinalysis—may reveal inadequately 
concentrated urinary specific gravity (often 
<1.025), proteinuria, glucosuria, or 
cylindruria. Casts may be one of the earliest 
indicators of acute kidney injury.
N/A
IMAGING
N/A
Renal biopsy may be indicated to determine 
cause of acute kidney injury and potential for 
reversibility, especially in patients that do not 
favorably respond to treatment as expected. 
The magnitude of renal morphologic changes 
may appear mild compared to the magnitude 
of azotemia.
Most nephrotoxic drugs cause proximal renal 
tubular necrosis.

Canine and Feline, Seventh Edition  975
N  TREATMENT
• Manage patients with acute kidney injury 
as inpatients.
• Manage patients without azotemia that can 
eat, and drink enough to maintain hydration, 
as outpatients.
• Administer balanced polyionic fluid (e.g., 
lactated Ringer’s solution).
• Correct hydration deficits rapidly (i.e., over 
6–8 hours) to minimize further renal injury. 
Calculate volume of fluid to administer as 
follows: volume (mL) = body weight (kg) ×% 
dehydration × 1,000 mL.
• In addition to correcting hydration deficits, 
administer maintenance requirements (~66 
mL/kg/day) unless the patient is oliguric or 
anuric, and replace any ongoing losses caused 
by vomiting and diarrhea or polyuria.
• Extracorporeal therapies such as hemodialysis, 
charcoal hemoperfusion, or therapeutic plasma 
exchange may be indicated for certain drugs 
before toxicity has manifest.
ACTIVITY
Reduce
DIET
• Outpatients can be fed their regular food.
• Avoid oral feeding until vomiting is 
controlled, but initiate nutritional support as 
early as possible with acute kidney injury.
• If oral feeding is not possible initially, 
consider total or partial parenteral nutrition.
• The appropriate nutritional composition 
for patients with severe acute kidney injury 
has not been determined.
• Patients that recover from drug ­induced 
nephrotoxicosis may develop chronic kidney 
disease, which should be managed by feeding 
a therapeutic renal diet indefinitely.
• Provide unlimited access to clean, fresh 
water at all times.
• If any signs of illness such as inappetence, 
vomiting, or diarrhea develop, return the 
patient immediately for veterinary care to 
minimize worsening of renal function.
• Avoid elective surgery until kidney disease 
• If surgery is necessary, administer fluids 
(5–20 mL/kg/h) during anesthesia to 
maintain adequate mean arterial blood 
pressure (>60 mmHg) and renal perfusion. 
Monitor urine output and adjust rate of fluid administration to maintain urine production 
of 1–2 mL/kg/h.
None
Do not use furosemide to promote diuresis in 
patients with aminoglycoside nephrotoxicosis.
• Avoid drugs that may worsen renal injury 
in patients with nephrotoxicosis, including 
NSAIDs, vasodilators, and ACE inhibitors.
• Use less toxic drugs when possible (e.g., 
carboplatin instead of cisplatin, other effective 
antimicrobials instead of aminoglycosides).
N/A
  FOLLOW-UP
• Weigh hospitalized patients several times 
daily to detect changes in fluid balance and 
adjust fluid therapy accordingly.
• Perform biochemical analysis, including 
electrolytes, every 1–2 days to evaluate 
severity of azotemia and to detect electrolyte 
and acid/base abnormalities.
• Patients receiving aminoglycosides—
perform urinalysis every 1–2 days to detect 
early signs of nephrotoxicosis such as 
glucosuria, increased proteinuria, and 
cylindruria; discontinue aminoglycoside if 
any of these signs are observed.
• Measure urine output to determine if 
patient is polyuric or oliguric; adjust fluid 
therapy on the basis of these findings and 
determine need for additional treatment to 
stimulate urine production. Do not 
overhydrate patient with parenteral fluids.
• Avoid or correct risk factors that predispose to 
development of drug ­induced nephrotoxicosis.
• Initiate saline diuresis to all dogs receiving 
cisplatin.
• Avoid using nephrotoxic drugs unless they 
are necessary (e.g., use aminoglycosides only 
if patient has overwhelming sepsis and culture 
results indicate aminoglycosides are the only 
effective antimicrobial).
• Monitor serum aminoglycoside 
concentration and perform frequent 
urinalyses while administering an aminoglycoside; cylindruria may precede 
changes to urine concentration.
• Do not administer furosemide with an 
aminoglycoside as this combination is likely 
to enhance nephrotoxicity of the 
aminoglycoside.
• Acute kidney injury.
• Patients without azotemia may develop 
acute kidney injury after several days of 
exposure, especially to aminoglycosides.
• Renal injury caused by nephrotoxic drugs 
may lead to development of chronic kidney 
disease months to years after recovery from 
drug­induced renal injury.
N/A
N/A
N/A
SEE ALSO
Acute Kidney Injury.
drug.
Behrend EN, Grauer GF , Mani I, et al. 
Hospital ­acquired acute renal failure in 
dogs: 29 cases (1983–1992). J Am Vet Med 
Assoc 1996, 208:537–541.
Cowgill L, Langston C. Acute kidney 
insufficiency. In: Bartges J, Polzin D, eds., 
Ames, IA: John Wiley & Sons, 2011, pp. 
472–523.
Langston C. Acute uremia. In: Ettinger SJ, 
Elsevier, 2009, pp. 1969–1985.
Vaden SL, Levine J, Breitschewerdt EB. A 
retrospective case ­control of acute renal 
failure in 99 dogs. J Vet Intern Med 1997, 
11:58–64.
Author  Cathy E. Langston
Allyson C. Berent.(continued)  Nephrotoxicity, Drug-Induced

976  Blackwell’s Five-Minute Veterinary Consult  
N
Nerve Sheath Tumors
  BASICS
OVERVIEW
• T umors of the peripheral nerves, spinal 
nerves, or nerve roots. • Malignant peripheral 
nerve sheath tumor is the recommended 
denomination for these tumors, instead of 
schwannoma, neurilemmoma, or neuro­
fibroma, since determination of the cell of 
origin is often impossible. • Most tumors 
(80%) occur in the thoracic limb of dogs. 
• Approximately 50% of the tumors are 
located in the plexus or peripheral nerve 
region and 50% in the nerve root region.
• Dogs—no breed or gender predisposition. 
• Mean age in dogs—7.9 years; uncommon 
in dogs younger than 3 years. • Rare in cats.
SIGNS
• Chronic progressive thoracic limb lameness. 
• Muscle atrophy (neurogenic atrophy) often 
present, more severe than that observed with 
orthopedic disorders. • Decreased muscle 
tone and decreased flexor reflex can be 
observed. • Axillary palpation detects a mass 
in less than 30% of cases. • Axillary pain 
upon palpation occasionally. • Horner’s 
syndrome can be seen in tumors involving the 
T1–T3 nerve roots. • Ataxia, paresis, and 
asymmetric proprioceptive deficits can be 
seen if the tumor compresses the spinal cord. 
• Cutaneous trunci reflex may be poor to 
absent on the affected side. • In lumbosacral 
tumors, rectal palpation can be useful for 
mass detection. • Self­mutilation is 
occasionally observed.
Mutation of the neu oncogene was identified 
in some cases.
  DIAGNOSIS
• Orthopedic conditions causing thoracic or 
pelvic limb lameness. Differentiate by 
orthopedic examination, radiographs, 
scintigraphy, CT, or MRI and response to rest 
and anti ­inflammatory drugs. The severity of 
muscle atrophy also useful. • Lateralized 
nerve root compression by intervertebral disc 
disease, lumbosacral disease (cauda equina 
syndrome), or spinal neoplasia. Intervertebral 
disc disease and lumbosacral disease are 
usually associated with spinal pain. Advanced 
imaging (CT or MRI) is required to 
distinguish these diseases. • Secondary nerve 
neoplasia—lymphoma, histiocytic sarcoma, 
chondrosarcoma. Fine ­needle or core biopsy 
needed to differentiate these conditions.OTHER LABORATORY TESTS
• CSF analysis—nonspecific findings. 
• Cytology—ultrasound (US) ­guided 
fine­needle biopsy can provide diagnostic 
sample. Cytologic features of malignant 
peripheral nerve sheath tumor (MPNST) are 
characteristics of a soft tissue sarcoma.
IMAGING
• Survey radiographs—well ­positioned survey 
radiographs may allow visualization of an 
enlarged intervertebral foramen; most often 
unrewarding. • US—can identify a mass in 
cases where axillary palpation is unrewarding in 
distally located tumors. Patient sedation allows 
better positioning and US ­guided fine ­needle 
aspiration biopsy. T umor echogenicity is variable. 
• Myelography—if the neoplasm has invaded 
the vertebral canal, an intradural extra­
medullary pattern can be seen. Due to the 
location of neoplasms, myelography is 
diagnostic in approximately 50% of dogs. 
• CT and MRI—to visualize proximal or 
distal limb tumors. Hyperintensity on 
T2­weighted images is the most common 
MRI pattern. MPNSTs usually show contrast 
enhancement on both CT and MRI. Due to 
the high soft tissue characterization, MRI is 
the diagnostic modality of choice.
• Electromyography (EMG)—to differentiate 
neurogenic from disuse muscle atrophy. 
Fibrillation potentials and positive sharp 
waves are suggestive of neurogenic muscle 
atrophy. EMG changes found in 96% of dogs 
with confirmed or suspected nerve sheath 
tumors. Epaxial muscle EMG changes 
predictive of vertebral canal invasion in cases 
of proximal tumors. • Nerve conduction 
velocity—conduction velocities may be 
prolonged with amplitude reduced. • F­wave, 
H­wave, cord dorsum potentials—evaluate 
the root portion of the nerve and can be 
useful to differentiate a lesion affecting 
predominantly the sensory or motor root.
  TREATMENT
• Surgical resection following the principles of 
oncologic surgery is the recommended treat  ­ 
ment. • Local resection with clean margins was 
recently shown to yield very long survival times. 
• Amputation is also an option for large size 
tumors. • Hemilaminectomy or dorsal 
laminectomy may be required to allow resection 
of the nerve root region. • Oral corticosteroids 
may allow clinical improvement by reduction of 
peritumoral edema. • Radiation therapy—can 
be used for nonresectable tumors or in cases 
where surgery is contraindicated. It can also be 
used postoperatively to decrease the chance of 
local recurrence.  MEDICATIONS
• Chemotherapy—metronomic therapy 
(cyclophosphamide 10 mg/m2 and piroxicam 
0.3 mg/kg) can be used for incompletely 
resected nerve sheath tumors in dogs. 
• Dexamethasone 0.1–0.25 mg/kg q24h or 
prednisone 0.5–1 mg/kg q12–24h can be 
used to provide short ­term improvement. 
• Gabapentin 5–20 mg/kg q8–12h can be 
used for analgesia in cases of neuropathic 
pain. • Pregabalin 2–4 mg/kg q12h can be 
used in cases refractory to gabapentin.
  FOLLOW-UP
• Nerve sheath tumors are locally invasive 
and rarely metastasize. • Postoperative local 
recurrence is common (up to 72% of cases).
• MPNST = malignant peripheral nerve 
sheath tumor.
• US = ultrasonography.
da Costa RC, Parent JM, Dobson H, et al. 
Ultrasound ­guided fine needle aspiration in 
the diagnosis of peripheral nerve sheath 
tumors in 4 dogs. Can Vet J 2008, 
49:77–81.
Lacassagne K, Hearon K, Berg J, et al. Canine 
spinal meningiomas and nerve sheath 
tumours in 34 dogs (2008 ­2016): 
distribution and long ­term outcome based 
upon histopathology and treatment 
modality. Vet Comp Oncol 2018, 
16(3):344–351.
van Stee L, Boston S, Teske E, Meij B. 
Compartmental resection of peripheral 
nerve tumours with limb preservation in 16 
dogs (1995–2011). Vet J 2017, 226:40–45.

Canine and Feline, Seventh Edition  977
N
Neuroaxonal Dystrophy
  BASICS
OVERVIEW
• Inherited degenerative diseases of neurons 
in diverse regions of the CNS, particularly the 
cerebellum and associated pathways.
• Primary neuroaxonal dystrophy disorders 
are sometimes classified as abiotrophies.
• Inheritance—autosomal recessive in breeds 
where heritability is proven.
• The main pathologic feature of neuroaxonal 
dystrophy, axonal spheroids, also occurs in 
normal aging, as well as secondary to a 
number of other diseases, such as acquired or 
inherited metabolic diseases, and toxicities.
• Breeds predisposed—domestic and Siamese 
cats, Rottweilers, collies, papillons, 
Chihuahuas, German shepherd dogs, Jack 
Russell terriers, and boxers.
• Age at onset—breed-specific, ranging from 
under 2 months of age in cats, Chihuahuas, 
and papillons, to 1–2 years in Rottweilers.
SIGNS
• Cerebellar ataxia—progressive dysmetria 
and hypermetria of the limbs (rarely 
hypometria) with patellar hyperreflexia.
• Strength and proprioception normal in 
most cases. Rottweilers may have extensive 
involvement of the dorsal columns of the 
cervical spinal cord and may exhibit 
proprioceptive deficits.
• Loss of menace responses despite normal 
vision and facial nerves.
• Progressive signs of brainstem involvement 
may be a feature, especially in papillons, 
including loss of swallowing reflex and 
abnormal tongue movement; tetraplegia may 
develop in the final stages.
• Mild intention tremors or head and neck 
dysmetria in some patients.
• Primarily cerebellar signs in Rottweilers, 
collies, Chihuahuas, and domestic cats; 
predominantly spinal cord lesions in German 
shepherd dogs and boxers; tremors and 
cerebellar ataxia present in all affected animals.
• Unknown.
• Usually classified as neuronal abiotrophy.
• Autosomal recessive inheritance proven in 
• Breed predisposition.
  DIAGNOSIS
• Suspicion is based on clinical signs in a 
predisposed breed, usually in juvenile animals.
• Definitive diagnosis requires histo  pathologic 
examination of CNS tissue, usually post-mortem.DIFFERENTIAL DIAGNOSIS
• Other congenital cerebellar anomalies, 
abiotrophies, and degenerative disorders. 
Reported occasionally in cats, and in a 
number of breeds of dog including border 
collie, Brittany, coton de T ulear, Gordon 
setter, Jack Russell (Parson Russell) terrier, 
Labrador retriever, Old English sheepdog, 
and many others.
• Other structural anomalies of the caudal 
brainstem, including caudal occipital 
malformation syndrome and Dandy–Walker 
syndrome. Differentiated by imaging studies, 
particularly MRI. Certain breeds are 
predisposed, e.g., caudal occipital malformation 
syndrome in the cavalier King Charles spaniel.
• Cerebellar hypoplasia caused by in utero  
infection of kittens with feline panleukopenia 
virus—apparent by 3–6 weeks of age; 
• Distemper encephalitis—differentiated on 
the basis of systemic signs preceding or 
accompanying the neurologic deficits and on 
results of CSF analysis (normal with neuro -
axonal dystrophy).
• Other infectious encephalitides—fungal, 
rickettsial, and protozoal; differentiated on 
the basis of multisystemic signs in some 
patients, serologic testing, and CSF analysis.
• Noninfectious inflammatory 
encephalitides, particularly granulomatous 
meningoencephalomyelitis. Breed-specific 
encephalitides (pug, Maltese terrier, Yorkshire 
terrier) usually cause forebrain signs 
(seizures), but cerebellar involvement may 
occur. Differentiated by the presence of 
inflammatory changes in CSF and, in some 
cases, by contrast-enhancing lesions in the 
brain apparent with MRI.
• Neoplasia affecting the cerebellum—
primary, metastatic, or locally invasive. Occurs 
in older dogs and cats, usually over 5 years of 
age. Differentiated on the basis of imaging 
studies (particularly MRI), CSF analysis in 
some cases, and systemic involvement in the 
case of metastatic neoplasia.
• Cervical spinal cord disease—proprioceptive 
deficits and tetraparesis.
• Diagnosis of neuraxonal dystrophy is by 
exclusion; it may not be possible to reach an 
antemortem diagnosis.
Normal
IMAGING
Atrophy of the cerebellum may be appreciable 
on MRI in certain patients (e.g., papillons).
• Axonal spheroids—present throughout the 
CNS gray or white matter, depending on the 
breed affected. Spheroids contain abnormal 
accumulations of intracellular proteins, 
particularly several associated with axonal 
transport and synaptic function.• Myelin degeneration may occur secondary 
to axonal pathology.
  TREATMENT
• None available that alters the course of the 
disease.
• Activity—restrict activity to areas where a 
fall can be avoided (avoid stairs, swimming 
pools, etc.).
N/A
  FOLLOW-UP
• Rottweilers—worsen over 1–5 years; 
develop clonic patellar and crossed extensor 
reflexes.
• Not fatal, but severely incapacitating.
Diaz JV, Duque C, Geisel R. Neuroaxonal 
dystrophy in dogs: case report in 2 litters of 
papillon puppies. J Vet Intern Med 2007, 
21:531–534.
Nibe K, Kita C, Morozumi M, et al. 
Clinicopathological features of canine 
neuroaxonal dystrophy and cerebellar 
cortical abiotrophy in papillon and 
papillon-related dogs. J Vet Med Sci 2007, 
69:1047–1052.
Sanders SG, Bagley RS. Cerebellar diseases 
and tremor syndromes. In: Dewey CW, ed., 
A Practical Guide to Canine and Feline 
Neurology, 2nd ed. Ames, IA: Wiley-
Blackwell, 2008, pp. 300–301.

978  Blackwell’s Five-Minute Veterinary Consult  
N
Neutropenia
  BASICS
• Neutrophil count below the reference interval.
• Can occur alone or as a component of  
bi- or pancytopenia.
• Often accompanied by a left shift and toxic 
change (e.g., cytoplasmic basophilia, Döhle 
bodies, foamy cytoplasmic vacuolation, and/
or toxic granulation).
• Certain breeds (e.g., greyhound, Belgian 
Tervuren) can have a neutrophil count below 
the reference interval for other breeds.
Results from one of four mechanisms: (1) 
decreased production or release of neutrophils 
from the bone marrow, (2) a shift from the 
circulating pool within the large vessels to the 
marginating pool, (3) increased migration 
from blood into the tissues due to severe 
inflammation/tissue consumption, and (4) 
immune-mediated destruction.
Predisposes to infections, affecting many 
body systems in any combination, depending 
on the site(s) of infection.
GENETICS
• Cyclic hematopoiesis can result in 
intermittent neutropenia.
• A genetic trait with delayed penetrance 
results in age-related neutropenia in Belgian 
Tervuren dogs.
• Selective cobalamin malabsorption is an 
autosomal recessive trait in many breeds that 
results in neutropenia, including Imerslund–
Gräsbeck syndrome in border collies.
• An autosomal recessive neutropenia 
(trapped neutrophil syndrome) in border 
collies from Australia and New Zealand is 
characterized by a deficiency of circulating 
segmented neutrophils and myeloid cell 
hyperplasia in the bone marrow.
• Not specific for secondary infections.
• Schnauzers, beagles, Australian shepherd 
dogs, shar-peis, Komondorok, and border 
collies can have heritable cobalamin 
• Grey collies and possibly border collies and 
Basset hounds may exhibit cyclic hematopoiesis.
• Aged Belgian Tervurens.
• Related border collies in Australia and New 
Zealand can have chronic neutropenia.
• Rottweiler dogs overrepresented for 
granulocyte colony-stimulating factor 
(G-CSF) deficiency.
SIGNS
• Septic animals usually have nonspecific signs. 
Fever is common, but normothermia does not 
exclude infection. Septic shock may be present.• Grey collies with cyclic hematopoiesis exhibit 
severe neutropenia every 12–14 days. Episodes 
of fever, diarrhea, gingivitis, respiratory 
infection, lymphadenitis, and arthritis occur in 
association with the neutropenia.
• No clinical signs in Belgian Tervurens.
CAUSES
Deficient Neutrophil Production, Stem 
Cell Death, or Inhibition
• Infectious agents—parvovirus, bacteria-
induced myelonecrosis, systemic mycosis 
(dogs and cats); feline leukemia virus (FeLV) 
and feline immunodeficiency virus (FIV) 
(cats); monocytic and granulocytic 
ehrlichiosis, babesiosis (dogs).
• Drugs, chemicals, and toxins—chemotherapy 
agents and cephalosporins (dogs and cats); T-2 
mycotoxin ingestion, chloramphenicol and 
benzene-ring compounds, methimazole, and 
griseofulvin (cats); estrogen, phenylbutazone, 
trimethoprim–sulfadiazine, phenobarbital 
(dogs).
• Lack of trophic factors—inherited 
malabsorption of cobalamin/vitamin B12.
• Ionizing radiation.
Reduced Hematopoietic Space 
(Myelophthisis)
• Myelonecrosis.
• Myelofibrosis.
• Disseminated neoplasia, leukemia, or 
myelodysplastic syndrome.
• Disseminated infectious disease (e.g., 
histoplasmosis, cryptococcosis,  
leishmaniasis).
Cyclic Stem Cell Proliferation
• Inherited cyclic hematopoiesis.
• Cyclophosphamide treatment.
• Idiopathic disease.
• Immune-mediated suppression of 
granulopoiesis.
Neutrophil Migration
A shift in neutrophils from the circulating 
pool to the marginating pool can occur in 
patients with endotoxemia or anaphylaxis.
Reduced Survival
• Severe bacterial infection—sepsis, 
pneumonia, peritonitis, pyothorax,  
pyometra.
• Immune-mediated destruction.
• Drug-induced destruction.
• Hypersplenism (sequestration).
• Inherited disease—cyclic hematopoiesis, 
cobalamin malabsorption as noted earlier.
• Drug or toxin exposure.
• Infectious agents exposure (e.g., in kennels 
or catteries): Ehrlichia canis , parvovirus, 
Bordetella bronchiseptica  (causing secondary 
pneumonia) (dogs); panleukopenia, FIV, and 
FeLV infection (cats).  DIAGNOSIS
• Most neutropenias are due to nonbacterial 
infectious diseases (e.g., FeLV, FIV, systemic 
mycoses, parvoviruses).
• Acute bacterial infection with marked 
inflammation and/or endotoxemia.
• Direct cytotoxic effects of drugs or toxins 
on myeloid stem cells.
• Primary bone marrow disease.
• Immune-mediated destruction (diagnosis of 
exclusion).
• Inherited disease (more likely in younger 
animals unless adult-onset).
• Diagnosis is verified by CBC with blood 
smear evaluation.
• Serial CBCs may be necessary to confirm 
neutropenia or detect cyclic hematopoiesis.
• Urinalysis to identify urinary tract 
Factors That May Erroneously Alter 
• Inadequately mixed blood sample.
• Partial clotting of the specimen.
• Leukergy/leukocyte agglutination caused by 
antibody-related factors, leading to incorrect 
counting by automated machines. May rarely 
occur as a temperature-dependent 
phenomenon, resolved by warming the 
sample to 37°C (98.5°F).
• Infectious disease screening—serologic or 
molecular testing for infectious organisms.
• Detection of antineutrophil antibodies by 
flow cytometry and observation of leuko -
agglutination identifies immune-mediated 
neutropenia (IMN).
• Aerobic or anaerobic microbial culture of 
blood or areas of bacterial infection when 
IMAGING
Survey radiography or ultrasonography may 
identify sites of infection or inflammation.
DIAGNOSTIC PROCEDURES/
• Bone marrow aspirate and core biopsy—to 
evaluate neutrophil precursors; a higher 
percentage of myeloblasts may be seen in 
animals rebounding from neutropenia, and 
should not be misdiagnosed as acute 
leukemia. Patients with IMN have myeloid 
hyperplasia with a left-shift, but hypoplasia 
can be seen if antibodies are precursor- 
directed.
• Cytologic examination of tissues—to 
verify neutrophil presence in body cavity 
effusions or tissues, confirm bacterial 

Canine and Feline, Seventh Edition  979
N
• Genetic testing or identification of 
abnormal urine metabolites may identify dogs 
with cobalamin malabsorption.
  TREATMENT
• Primary concern is the presence or 
development of infection.
• Nonfebrile patients—prophylactic 
broad-spectrum oral antibiotics that spare 
normal gastrointestinal flora are indicated.
• Febrile patients—suggests infection; 
inpatient treatment recommended for further 
diagnostic testing and therapy with IV 
broad-spectrum antibiotics and other therapies 
(e.g., IV fluids, surgery) as indicated.
• Nonfebrile patients—cephalexin 30 mg/kg 
PO q12h or enrofloxacin 10 mg/kg PO q24h; 
cephalosporins or other classes of anti -
microbials are contraindicated if thought to 
be the trigger for neutropenia.
• Febrile patients—ampicillin 22 mg/kg IV 
q6–8h or ampicillin + sulbactam 22–30 mg/kg 
IV q8h and enrofloxacin 10 mg/kg IV q24h 
(caution in cats) or cefotaxime 50 mg/kg IV 
q6–8h (dogs), 20–60 mg/kg IV q6–8h (cats).
• If clinically warranted, metronidazole 10 mg/
kg IV q12h provides anerobic bacterial coverage.
• Recombinant human G-CSF (rhG-CSF) 
5–10 μg/kg/day SC for 3–6 doses may 
stimulate short-term neutrophil production, 
but can result in production of neutralizing 
antibodies in 14–21 days, which may 
crossreact with endogenous G-CSF; 
ineffective in canine parvovirus.
• IMN—prednis(ol)one 1 mg/kg PO q12h, 
additional immunosuppression from either azathioprine 1–2 mg/kg PO q24h (dogs), 
0.3 mg/kg PO q24h (cats), cyclosporine 
3.3–6.7 mg/kg PO q24h, or mycophenolate 
7–20 mg/kg PO q12h (dogs), 7–10 mg/kg 
PO (cats) may be necessary.
  FOLLOW-UP
• Neutropenia is likely to occur 7–10 days 
after administration of most 
chemotherapeutic drugs but may develop as 
late as 2–3 weeks following lomustine 
(CCNU) or carboplatin administration.
• Improvement is generally denoted by a 
rising leukocyte or neutrophil count, 
resolution of left shift, and disappearance of 
toxic changes on CBC analysis.
• Rebound neutrophilic leukocytosis is 
expected during recovery from neutropenia.
• The accelerated neutrophil production 
following rhG-CSF therapy can result in 
toxic-appearing and left-shifted neutrophils in 
Secondary infections.
Viral or bacterial infection, sepsis, chemotherapy.
Middle-aged and older animals are less 
effective at repopulating the bone marrow 
with hematopoietic cells after an insult, due 
to age-related reduction in stem cell numbers.
Pregnant Animals
• Drugs listed should be used only if the 
benefits supersede the inherent risks.• Adequately controlled safety studies of 
rhG-CSF have not been performed in dogs 
and cats (including pregnant animals).
SEE ALSO
• Cobalamin deficiency.
• Cyclic Hematopoiesis.
factor.
• IMN = immune-mediated neutropenia.
• rhG-CSF = recombinant human 
granulocyte colony-stimulating factor.
Devine L, Armstrong PJ, Whittemore JC, 
et al. Presumed primary immune-mediated 
neutropenia in 35 dogs: a retrospective 
study. J Small Anim Pract 2017, 
58:307–313.
Schnelle AN, Barger AM. Neutropenia in 
dogs and cats: causes and consequences. Vet 
Clin North Am Small Anim Pract 2012, 
42:111–122.
Thrall MA, Weiser G, Allison R, Campbell 
Chemistry, 2nd ed. Ames, IA: John Wiley 
& Sons, 2012.
Vail DM. Supporting the veterinary cancer 
patient on chemotherapy: neutropenia and 
gastrointestinal toxicity. Top Companion 
Anim Med 2009, 24:122–129.
Authors  Francisco O. Conrado and Jennifer 
L. Owen
Consulting Editor  Melinda S. Camus(continued)  Neutropenia

980  Blackwell’s Five-Minute Veterinary Consult  
N
Nocardiosis/Actinomycosis—Cutaneous
  BASICS
OVERVIEW
Nocardiosis and actinomycosis are deep 
suppurative or pyogranulomatous cutaneous 
infections caused by bacteria of the genera 
Nocardia  or Actinomyces  and Arcanobacteria  
(respectively). Infection arises from direct 
inoculation of the organisms into the skin. 
Nocardia  spp are ubiquitous soil and water 
saprophytes: Infection is usually a conse-
quence of inoculation via scratch, bite or 
foreign body penetrating wound. Actinomyces  
and Arcanobacteria  are normal inhabitants of 
the oropharynx and infection frequently 
follows a bite wound. Infection typically 
remains restricted to the skin, but dissemina-
tion to internal organs (lungs) can occur in 
both diseases.
Dogs and cats with access to the outdoors are 
SIGNS
Cutaneous lesions in both infections consist of 
nodules, subcutaneous swellings or abscesses 
that often develop draining sinuses. Diffuse 
cellulitis with numerous draining tracts may 
occur. In actinomycosis, draining tracts 
discharge a thick yellow-gray or hemorrhagic 
exudate that may contain sulfur granules. In 
nocardiosis the discharge is less abundant. 
Lesions are typically located on areas of 
wounds as limbs, feet, thorax, or abdomen. 
Regional lymphadenopathy is common.
Nocardia  (most commonly N. cyriacigeorgica , 
N. nova , N. abscessus , N. farcinica , and N. 
otitisdiscaviarum ) are Gram-positive, partially 
acid-fast, branching filamentous aerobic 
bacteria with worldwide distribution. 
Actinomyces  (most commonly A. bowdenii , A. 
canis, A. viscosus, A. odontolyticus,  A. meyeri , 
and Arcanobacterium pyogenes ) are Gram-
positive, non-acid fast, filamentous anaerobic 
rods that are opportunistic commensals of the 
oral cavity and bowel. Most Actinomyces  
infections are complicated by mixed 
infections with other bacteria.
  DIAGNOSIS
Diagnosis is by skin biopsy obtained for 
culture and histopathology. Nocardia  is easily 
cultured under aerobic conditions. Actinomyces  
has fastidious growth requirements and may 
be slow-growing and/or difficult to grow. 
Species identification may require a 
specialized laboratory. Fine-needle aspiration 
for cytology and culture may also be useful.DIFFERENTIAL DIAGNOSIS
Other systemic fungal infections, subcutaneous 
mycosis, panniculitis (sterile or due to 
mycobacterial infection), bacterial pseudomy-
cetoma, and foreign body reactions.
Usually subtle. May vary according to the 
extent and duration of disease. Extensive, 
chronic, or disseminated disease may cause a 
mild to moderate nonregenerative anemia, 
leukocytosis, neutrophilia, and monocytosis. 
Hypercalcemia due to granulomatous disease 
can be present.
IMAGING
Thoracic radiography and abdominal 
ultrasound are recommended to assess for 
dissemination of infection.
Histopathologic lesions consist of granulo -
matous to pyogranulomatous dermatitis and 
panniculitis accompanied by extensive 
fibrosis. Special stains are used to identify 
microorganisms in tissues. Granules of 
actinomycosis are basophilic with an 
eosinophilic periphery (Splendore–Hoepli 
phenomenon).
  TREATMENT
Surgical drainage of abscesses or surgical 
debridement followed by long-term antibiotic 
administration is recommended. T reatment 
must be continued at least 1 month after 
clinical cure.
Nocardiosis
Sulfonamides (trimethoprim-sulfonamide 30 
mg/kg q12h). Clinical improvement should 
be observed within 2 weeks. Susceptibility 
testing is strongly recommended in cases that 
fail to respond to empirical treatment or in 
cases of relapse. T reatment success with 
alternative antibiotics, including amikacin, 
cephalosporins, clarithromycin, and 
doxycycline, has been reported.
Actinomycosis
High-dose penicillin (penicillin G 40 mg/kg 
q8h). Strains of Actimomyces  spp. have not 
shown resistance to penicillin. For animals 
not tolerating penicillin, alternative anti -
biotics include clindamycin, erythromycin, 
and doxycycline.
Caution advised with use of sulfonamides in 
Doberman pinschers.  FOLLOW-UP
Prolonged treatment with monitoring is 
required. Prognosis is guarded, although most 
immunocompetent animals with only 
cutaneous infection and properly treated are 
usually cured.
No cases of human of actinomycosis or 
nocardiosis acquired from direct contact with 
a dog or cat with clinical disease have been 
reported. Rare cases of cutaneous actinomycosis 
or nocardiosis in humans as a consequence of 
a scratch or bite from a cat or dog have been 
reported. Pet owners, veterinarians, and nurses 
should wear protective gloves when handling 
infected dogs and cats to avoid inadvertent 
infection through damaged skin.
Greene CG, ed., Infectious Diseases of the 
Elsevier, 2012, pp. 484–495.
Resnick

Canine and Feline, Seventh Edition  981
N
Nonsteroidal Anti-inflammatory Drug Toxicosis
  BASICS
• Toxicosis secondary to the acute or chronic 
ingestion of a nonsteroidal anti-inflammatory 
drug (NSAID). • NSAIDs—classed as 
carboxylic acids (aspirin, indomethacin, 
sulindac, ibuprofen, naproxen, carprofen, 
meclofenamic acid, etodolac, flunixin 
meglumine) or enolic acids (phenylbutazone, 
dipyrone, meloxicam, tepoxalin, and 
piroxicam); selective cyclooxygenase-2 
(COX-2) inhibitors (deracoxib, firocoxib, 
mavacoxib (Europe), and robenacoxib). 
• Newer selective COX-2 inhibitors and 
NSAIDs with preferential activity against 
COX-2 may have fewer adverse reactions than 
older COX-1 inhibitors, though both pathways 
may be inhibited following overdose.
• Action—analgesic, antipyretic, and 
anti-inflammatory due to the inhibition of 
cyclooxygenase; decreases production of 
prostaglandins that act as mediators of 
inflammation. • Well absorbed orally. 
• Clearance—varies greatly among species; 
eliminated slowly in dogs and cats; half-life 
varies significantly among NSAIDs. 
• Metabolized in the liver to active or inactive 
metabolites. • Excreted in the kidney via 
glomerular filtration and tubular secretion, 
and/or biliary excretion.
• Gastrointestinal (GI)—irritation, erosions, and 
ulcerations. • Renal/urologic—acute kidney 
injury; acute interstitial nephritis. 
• Hepatobiliary—idiosyncratic hepatocellular 
damage. • Hemic/lymphatic/immune—bleeding 
disorders from decreased platelet aggregation. 
• Nervous – ataxia, seizures, CNS depression, 
and coma may occur with very large doses.
GENETICS
• Very large species differences in absorption, 
excretion, and metabolism of different agents; 
avoid extrapolation of data from other species 
or dosages. • Off-label use of NSAIDs can 
result in significant, potentially life-
threatening adverse effects in all species, 
especially cats. • Over-the-counter NSAIDs 
(especially ibuprofen and naproxen) are 
common causes of NSAID toxicosis in dogs 
and cats. Naproxen has an extremely long 
half-life in domestic animals and exposures 
carry a high risk of significant adverse effects.
Among the 10 most common toxicoses 
reported to both the Pet Poison Helpline 
(PPH) and the American Society for the 
Prevention of Cruelty to Animals (ASPCA) 
Animal Poison Control Center (APCC).GEOGRAPHIC DISTRIBUTION
N/A
• Dogs and cats. • Cats are more sensitive. 
• No breed or gender predilections.
SIGNS
• GI irritation—within a few hours. • Renal 
involvement or GI ulceration—may be 
delayed several days.
• Evidence of accidental consumption of 
medication or reported administration of an 
NSAID (either prescribed or unprescribed). 
• Lethargy. • Anorexia. • Vomiting—with or 
without blood. • Diarrhea. • Icterus. 
• Melena. • Polyuria, polydipsia, and oliguria. 
• Ataxia, seizures, coma—may occur with 
large ingestions. • Collapse and sudden death—
may occur from a perforated gastric ulcer.
• Depression. • Pale mucous membranes. 
• Painful abdomen. • Dehydration. • Fever. 
• Tachycardia. • Icterus.
CAUSES
Accidental exposure or inappropriate 
Toxic Doses for Common NSAIDs
• Carprofen: ◦ Dogs: 20 mg/kg—GI 
ulceration; 40 mg/kg—renal injury. ◦ Cats: 4 
mg/kg—GI ulceration; 8 mg/kg—renal 
injury. • Ibuprofen: ◦ Dogs: 50 mg/kg—GI 
ulceration; 100–175 mg/kg—renal injury; 
400 mg/kg—CNS signs. ◦ Cats: considered 
about twice as sensitive as dogs. • Naproxen: 
◦ Dogs: 5 mg/kg—GI ulceration; 25 mg/
kg—severe renal injury (may occur at lower 
doses); 50 mg/kg—CNS signs. ◦ Cats: 
considered at least twice as sensitive as dogs.
• Age—neonatal or geriatric. • Previous history 
of GI disease, ulcer, or bleeding. • Preexisting 
renal, hepatic, or cardiovascular disease. 
• Hypotension; dehydration or hypovolemia. 
• Other concurrent illness and/or medications 
(especially other NSAIDs or corticosteroids).
  DIAGNOSIS
Other conditions that cause GI and/or renal 
effects:
• Inflammatory bowel disease, hemorrhagic 
gastroenteritis, hypoadrenocorticism, GI 
foreign body, neoplasia, ethylene glycol 
toxicosis, lily ingestion (cats), grape/raisin 
ingestion (dogs), renal failure (acute or 
chronic), urinary tract obstruction, pyelonephritis. • Diagnosis based on history 
of exposure and compatible clinical signs.
• Anemia—regenerative or nonregenerative, 
depending on duration of bleeding. 
• Leukocytosis with left shift—associated 
with perforated gastric ulcer and 
accompanying peritonitis. • BUN and 
creatinine—may be elevated secondary to 
prerenal azotemia or primary renal insult. 
• Panhypoproteinemia – secondary to GI 
bleeding. • Liver enzymes—occasionally 
elevated. • Monitor urine output for evidence 
of oliguria; monitor for isosthenuria, 
glucosuria, proteinuria, and casts.
N/A
IMAGING
N/A
Endoscopy—verify GI ulceration.
• GI irritation, ulceration, or hemorrhage 
with possible perforation and peritonitis. 
• Renal tubular or papillary necrosis or 
interstitial nephritis.
  TREATMENT
• Outpatient—mild clinical signs (with low 
ingested dose); managed at home with 
appropriate medication and dietary and 
symptomatic measures. • Inpatient—high 
ingested dose; potential for renal toxicosis; 
more serious clinical signs (frequent 
vomiting, bloody vomitus, melena, anemia, 
or evidence of renal involvement); aggressive 
treatment to avoid life-threatening 
Recent Ingestion
• Ingestion within 2 hours and no vomiting—  
induce emesis (apomorphine or hydrogen 
peroxide), only if patient not at-risk for 
aspiration. • After emesis—activated charcoal 
(1–2 g/kg PO) with a cathartic ×1 dose. 
• Repeat activated charcoal without a 
cathartic q6–8h ×2 doses for NSAIDs that 
undergo enterohepatic recirculation.
• Fluid therapy—restore hydration when 
moderate to severe vomiting; twice 
maintenance rates with known or potential 
renal involvement. Titrate fluids as needed 
based on clinical signs and blood work 
results. Use caution in patients with 
underlying cardiac disease to avoid fluid 
overload. • If severely anemic, a blood 
transfusion may be indicated.

982  Blackwell’s Five-Minute Veterinary Consult  
N
ACTIVITY
N/A
DIET
• Vomiting—NPO. • Vomiting resolved—
begin with a bland, low-protein diet.
• Stress the importance of contacting a 
veterinarian or animal poison control center 
(PPH or ASPCA APCC) whenever an animal 
is exposed to a nonprescribed NSAID or an 
overdose of a prescribed NSAID. • Inform 
client that dogs and particularly cats have a 
low tolerance to NSAIDs. • With a 
prescribed NSAID, instruct client to look for 
adverse or idiosyncratic effects and to stop the 
drug and contact the clinic if they occur.
Surgical intervention may be required for a 
perforated GI ulcer.
H2-Receptor Antagonists
• For GI upset or ulceration.
• Primarily effective for treating ulcers from 
acute overdose or from chronic admini -
stration after the drug withdrawn. 
• Famotidine or ranitidine may be best 
choices as cimetidine may inhibit microsomal 
enzymes that metabolize some NSAIDs. 
• Famotidine—dogs: 0.5–1.0 mg/kg PO, SC, 
IV, or IM q12–24h; cats: 0.5 mg/kg PO, SC, 
IV, or IM q12–24h. • Ranitidine—dogs: 2 
mg/kg PO, IV q8h; cats: 2.5 mg/kg IV q12h 
or 3.5 mg/kg PO q12h.
Proton Pump Inhibitors
• Omeprazole 0.5–1 mg/kg PO q24h. 
• Pantoprazole 0.7–1 mg/kg IV over 15 
minutes q24h.
Other
• Sucralfate—dogs: 0.5–1 g PO q8–12h; cats: 
0.25 g PO q8h; binds to proteins in the ulcer 
base; stimulates mucus and bicarbonate 
secretion. • Misoprostol 1–3 μg/kg PO q8h; 
prostaglandin E2 analogue; prevents GI 
bleeding and ulceration; promotes healing 
during chronic use in humans and dogs treated 
with aspirin.• Dopamine—may be indicated 
for acute renal failure. • Standard anticonvul -
sant therapy—diazepam, pheno  barbital, levetiracetam, etc. if needed. • Naloxone may 
be useful in comatose patients.
Duration of Treatment
Depends on the dose and half-life of the 
NSAID ingested.
Avoid concomitant use of corticosteroids or 
multiple NSAIDs; contraindicated in 
pregnancy (abortifacient effect).
Patients using other nephrotoxic drugs (e.g., 
aminoglycosides and angiotensin-converting 
enzyme [ACE] inhibitors)—at higher risk for 
developing NSAID nephropathy.
NSAIDs are highly protein-bound; may be 
affected by concurrent use of other highly 
protein-bound drugs.
  FOLLOW-UP
• Urine output—monitor for oliguria; 
examine for casts, protein, and glucose. 
• Stool and vomitus—check for GI bleeding 
(may not develop for several days). • BUN 
and creatinine—daily for several days (full 
extent of renal damage may not be 
immediately evident); recheck 2–3 days after 
discharge if hospitalized. • Packed cell 
volume/total solids—check q12–24h while 
hospitalized, then 2–3 days after discharge to 
monitor for GI bleeding.
• Store medications out of the reach of pets. 
• Discourage owners from medicating pet 
without veterinary supervision. • Appropriate 
laboratory tests for high-risk patients before 
beginning NSAID therapy.
• Perforation of a GI ulcer and peritonitis. 
• Irreversible acute and chronic renal 
failure.
• GI upset or ulceration—usually complete 
recovery with appropriate treatment. • Renal 
effects—generally reversible with early and 
aggressive treatment. • Acute hepatopathies—
generally resolve with early symptomatic 
treatment and discontinuation of the drug.  MISCELLANEOUS
• Exposure during pregnancy—risk for fetal 
cardiopulmonary and renal effects. • May 
prolong pregnancy, especially if administered 
during the third trimester and before the 
onset of labor.
SEE ALSO
• Aspirin Toxicosis.
drug.
• PPH = Pet Poison Helpline.
https://www.petpoisonhelpline.com/poison/
nsaids
Enberg TB, Braun LD, Kuzma AB. 
Gastrointestinal perforation in five dogs 
associated with the administration of 
meloxicam. J Vet Emerg Crit Care 2006, 
16(1):34–43.
KuKanich B, Bidgood T, Knesl O. Clinical 
pharmacology of nonsteroidal anti-
inflammatory drugs in dogs. Vet Anaes 
Analg 2012, 39(1):69–90.
McLean MK, Khan SA. Toxicology of 
frequently encountered nonsteroidal 
anti-inflammatory drugs in dogs and cats. 
42(2):289–306.
Talcott PA, Gwaltney-Brant SM. 
Nonsteroidal anti-inflammatories. In: 
Peterson ME, Talcott PA, eds., Small 
Animal Toxicology, 3rd ed. Philadelphia, 
PA: W.B. Saunders, 2013, pp. 687–708.
acknowledge the prior contribution of Judy 
Holding.Nonsteroidal Anti-inflammatory Drug Toxicosis  (continued)

Canine and Feline, Seventh Edition  983
N
Notoedric Mange
  BASICS
OVERVIEW
• A nonseasonal, intensely pruritic, highly 
contagious parasitic skin disease of cats caused 
by Notoedres cati .
• Mites burrow through the superficial skin 
between follicles causing intense pruritus.
• Can cause transient pruritus in humans.
• Domestic cats of all ages and both sexes.
• Fairly host-specific, but can also produce 
symptoms in dogs, cheetahs, raccoons, 
rabbits, coatis, palm civets, bobcats, ocelots, 
foxes, and humans.
• All in-contact cats usually develop clinical 
signs.
• Epizootic in localized areas.
• Endemic in large feral cat populations.
• T ransmission by direct contact: mite is very 
short-lived when off the host.
SIGNS
• Nonseasonal intense pruritus.
• Following exposure, initial pruritus may be 
mild, but progresses to severe.
• Change from mild pruritus to onset of 
severe pruritus (incubation period) of 3–6 
weeks may indicate eventual seroconversion 
and the development of hypersensitivity (IgG 
as well as humoral response).
• Rare individuals do not seroconvert, and 
therefore may not develop severe pruritus.
• Papules and crusts develop on pinnae and 
spread to eyelids, face, and neck (also known 
as “head mange”).
• Progresses to the legs, feet and perineum.
• Severe self-trauma leads to secondary 
lesions.
• Skin becomes thickened, lichenified, and 
covered with gray-yellow crust.
• Large patches of lesions and alopecia 
develop over the entire body if untreated.
• Unlike canine scabies, large numbers of 
mites are present on the skin.
• Peripheral lymphadenopathy often 
develops.
• Causes significant debilitation in severe cases.
Close contact with other cats.
  DIAGNOSIS
• Atopy.
• Cutaneous adverse reaction to food.
• Demodicosis.• Malassezia  dermatitis.
• Cheyletiellosis .
• T rombiculosis (chiggers).
• Otodectic dermatitis.
• Pemphigus erythematosus.
N/A
N/A
• Superficial skin scraping—relatively easy to 
find mites.
• Mite smaller than S. scabiei , with dorsal 
anus, typical dorsal concentric “finger print” 
striae, and only two pairs of forelegs 
protruding from the body line.
• Serum testing (ELISA) for mite antibody 
not available.
• Acetate tape impression—as sensitive as 
skin scraping.
  TREATMENT
• When scabicidal dips are used, the entire 
cat must be treated.
• T reatment failures occur if product is not 
applied to the face and ears.
• All in-contact cats should be treated.
• Response is usually quick if all in-contact 
animals are treated.
• Thorough cleaning of the cat’s environment 
may be helpful if severely contaminated.
• Systemic antibiotics—may be needed to 
resolve secondary bacterial folliculitis.
• Lime sulfur rinses 2–3%; apply to entire 
body weekly for 6–8 applications; clipping 
might be necessary to permit adequate 
contact with the skin.
• Ivermectin—effective; 0.2–0.3 mg/kg SC 
every 2 weeks for 2–3 treatments.
• Doramectin 0.2–0.3 mg/kg SC once.
• Selamectin—off-label; applied every 2 
weeks for three applications.
• Imidacloprid/moxidectin spot-on applied 
once or twice as directed on the label.
• Isoxazoline parasiticides—not FDA 
approved: single administration.
• Amitraz rinse may cause sedation.
• Lime sulfur has unpleasant odor and is 
staining.  FOLLOW-UP
Reinfestation may occur if contact with 
infested animals continues; the source of 
infestation must be determined (if possible) as 
well as all in-contact cats must be treated.
• Topical scabicidal treatments are more 
prone to failure because of incomplete 
application of the treatment solution.
• Persistent infection if not all in-contact 
• Response to therapy is rapid providing all 
in-contact animals are treated; symptoms 
should significantly reduce within 2 weeks of 
• There is no immunity from repeat 
infestation; clinical signs following a 
reinfestation are likely to be more rapid due 
to previous exposure and sensitization.
• Humans in close contact with an affected 
cat may develop a pruritic, papular rash 
(often on arms, chest, or abdomen).
• Human lesions are usually transient and 
resolve spontaneously following treatment of 
Hellman K, Petry G, Capari B, et al. 
T reatment of naturally Notoedres cati -
infested cats with combination of 
imidacloprid 10%/moxidectin 1% spot-on 
(Advocate/Advantage multi, Bayer). 
Parasitol Res 2013, 112:S57–S66.
Sampio KO, de Oliveira LM, Burmann PM, 
et al. Acetate tape impression test for 
diagnosis of notoedric mange in cats. J 
Feline Med Surg. 2017, 19(6):702–705.
Resnick

984  Blackwell’s Five-Minute Veterinary Consult  
N
Nystagmus
  BASICS
• Involuntary, rhythmic oscillation of the 
eyeballs.
• Jerk nystagmus—most common; slow eye 
movements in one direction with a rapid 
recovery phase in the opposite direction.
• Pendular nystagmus—seen less frequently; 
characterized by slow oscillations of the eyes 
in a trajectory that resembles that of a 
pendulum, with no fast phase.
• Neural projections traverse in the 
brainstem from the vestibular nuclei to 
cranial nerve (CN) III, IV, and VI nuclei, 
which innervate the extraocular muscles. 
This pathway is part of the vestibular 
system, and provides coordinated conjugate 
eye movements in association with changes 
in head position.
• Physiologic nystagmus (ocular–vestibular 
reflex)—normal finding, induced by rotating 
the head from side to side; characterized by a 
jerk nystagmus with a slow drifting of the eye 
in the opposite direction of the head rotation 
followed by a fast compensatory phase in the 
same direction as the head movement. 
Decreased to absent physiologic nystagmus is 
indicative of vestibular disease.
• Pathologic nystagmus—a sign of vestibular 
dysfunction; characterized by a jerk nystagmus 
that develops independent of head movement. 
The nystagmus is described according to the 
axis of movement of the globe (horizontal, 
rotary, or vertical), and the direction of the 
fast phase of movement.
• Spontaneous or resting nystagmus—
pathologic nystagmus that occurs when the 
head is in a normal position and not moving; 
frequently resolves after several days.
• Positional nystagmus—pathologic 
nystagmus, elicited only when the head is 
placed in unusual position; can often be seen 
in more chronic conditions.
• Jerk nystagmus must be differentiated from 
pendular nystagmus and from opsoclonus.
• Pendular nystagmus—congenital 
abnormality in which a larger-than-usual 
portion of the optic nerve fibers crosses in the 
chiasm; most often observed as an incidental 
finding in Siamese, Birman, and Himalayan 
cats but can also be seen with cerebellar 
disease and with visual deficits.
• Opsoclonus—involuntary, rapid, random 
eye movements in multiple directions that 
can be seen with cerebellar disease; can be 
differentiated from jerk nystagmus by the lack 
of a slow phase and its chaotic nature.
NervousGENETICS
N/A
Nystagmus, as a sign of vestibular disease, is a 
relatively common clinical presentation in 
Species
None
Varies, depending on underlying cause; 
neoplastic and vascular conditions and canine 
geriatric vestibular disease more common in 
older animals.
None
CAUSES
Peripheral Vestibular Disease
• Neoplastic—nerve sheath tumor or 
tumor involving surrounding bone or soft 
tissues.
• Inflammatory—otitis media-interna; 
nasopharyngeal polyps (cats).
• Toxic—e.g., aminoglycosides, topical 
iodophors, topical chlorhexidine.
• T rauma.
Central Vestibular Disease
• Degenerative—storage disorders; 
neuronal degeneration; demyelinating  
disease.
• Neoplastic—primary or metastatic 
tumors.
• Inflammatory/infectious—viral (canine 
distemper, feline infectious peritonitis); 
bacterial; protozoal (toxoplasmosis, neosporo-
sis); fungal (cryptococcosis, blastomycosis, 
histoplasmosis, coccidioidomycosis, aspergil-
losis); rickettsial (ehrlichiosis, Rocky 
Mountain spotted fever); inflammatory, 
noninfectious (meningoencephalitis of 
unknown etiology; includes granulomatous 
meningoencephalomyelitis and the necrotizing 
meningoencephalitides).
• Toxic—lead; hexachlorophene; 
metronidazole.
• T rauma.
• Vascular—cerebrovascular disease 
(hemorrhage, infarction).
Systemic administration of certain antibiotics 
(metronidazole, aminoglycoside), otic 
administration of iodophors and 
chlorhexidine solutions.  DIAGNOSIS
• Nystagmus—either rotary or horizontal in 
character, with the fast phase directed away 
from the side of the lesion; does not change 
direction with different head positions.
• Other signs of vestibular disease—head tilt, 
ataxia, circling, falling or rolling, and 
vestibular strabismus often present and occur 
• Ipsilateral facial nerve deficits and/or 
Horner’s syndrome—can be seen due to the 
close association of CN VII and sympathetic 
nerve to CN VIII as they course through the 
petrous temporal bone.
• Nystagmus—horizontal, rotary, or vertical; 
can change direction with different head 
positions.
vestibular strabismus often present.
• Involvement of other brainstem 
structures—alterations in level of 
consciousness, paresis, postural reaction 
deficits, and other CN deficits (V and VII 
most common); deficits are typically 
• Paradoxical vestibular disease—with certain 
lesions of the cerebellum; in these cases, 
postural reaction deficits occur ipsilateral to 
the lesion whereas the head tilt and other 
vestibular signs are contralateral to the lesion.
Results usually normal
• Thyroid profile—if hypothyroidism is 
• Bacterial culture of sample obtained via 
myringotomy—if otitis media-interna is 
likely.
• Serologic testing—for potential infectious 
agents.
IMAGING
• Imaging of the tympanic bullae to assess for 
otitis media-interna—survey radiographs of 
limited value; CT and MRI are more 
• Brain imaging (CT or MRI)—indicated in 
animals with central vestibular disease to 
evaluate for structural brain abnormalities. 
MRI is superior to CT for imaging the brain.
CSF—if central disease, to evaluate for 
Variable, depending of the underlying cause

Canine and Feline, Seventh Edition  985
N
  TREATMENT
• The cause of the disease and the severity of 
signs determine whether the animal is best 
treated on an inpatient or an outpatient basis.
• In general, animals with central disease 
require more intensive care than those with 
peripheral disease.
• Fluid therapy is indicated in the acute 
stages of disease for animals that experience 
anorexia and vomiting.
• Animals with severe vestibular dysfunction 
should be confined to a well-padded area in 
the acute stage of the disease to minimize 
self-trauma secondary to disorientation.
ACTIVITY
• Animals should be housed on nonslippery 
surfaces; stairs should be avoided.
• Exercise should be supervised, with 
assistance provided until signs of imbalance 
resolve.
DIET
N/A
• Many animals show improvement over the 
first several days; the nervous system is able to 
compensate for vestibular disturbances that 
remain static or are slowly progressive 
regardless of cause.
• Compensation involves visual and somato -
sensory (tactile) cues and is dependent on 
feedback from vestibular pathways; return to 
normal activity should be encouraged to 
enhance compensatory mechanisms.
Signs of vestibular dysfunction can transiently 
worsen after an anesthetic episode; most 
likely reflects a loss of compensation.
• Meclizine (dogs: 4 mg/kg PO q24h) or 
maropitant (dogs: 1 mg/kg SC or 2 mg/kg PO q24h; cats: 1 mg/kg SC q24h)—used 
to treat motion sickness; can alleviate 
nausea and vomiting associated with acute 
disease.
• Diazepam (dogs: 0.5 mg/kg PO q8h)—
recommended in cases of metronidazole 
toxicity; can help decrease acute vestibular 
signs from other causes by decreasing the 
resting activity of vestibular neurons and 
alleviating the imbalance in vestibular input 
to the brain.
• Specific medical therapy is directed at the 
underlying cause, if one can be identified.
• Avoid potential ototoxic drugs, such as 
aminoglycosides. Toxicity is more likely in 
animals with renal impairment.
• Avoid instilling topical medications into the 
ear of an animal with suspected otitis 
media-interna, especially if the tympanic 
membrane cannot be visualized or is not 
intact. Such agents can exacerbate vestibular 
signs and cause deafness.
• Avoid the use of metronidazole at daily 
doses greater than 60 mg/kg, as this has been 
associated with vestibular dysfunction in 
dogs.
• Vestibular dysfunction can develop after 
administration of metronidazole at lower 
dosages but is less likely.
  FOLLOW-UP
Repeat neurologic examination—perform 2 
weeks after initial diagnosis to monitor for 
improvement or progression of disease.
N/A
• Dehydration and electrolyte imbalance 
associated with anorexia and vomiting.
• Rare extension of otitis media-interna into 
the adjacent brainstem.
• Prognosis varies, depending on the cause of 
the vestibular disturbance.• In general, animals with peripheral 
vestibular disease have a better prognosis than 
those with central involvement.
• Residual deficits can remain after resolution 
of the underlying disease process due to 
irreversible damage to the neural structures.
• Recurrence is possible with some of the 
conditions (otitis media-interna, canine 
geriatric vestibular disease, feline idiopathic 
vestibular disease).
N/A
N/A
N/A
SEE ALSO
• Ataxia.
• http://www.vetfolio.com/neurology/
vestibular-disease-diseases-causing-vestibular-
signs-compendium
• https://vestibular.org/sites/default/files/
page_files/Vestibular%20disease%20in%20
dogs%20and%20cats.pdf
Contin Educ Vet 2012, 34(7):E1–E5.
Author  Karen R. Muñana(continued)  Nystagmus

986  Blackwell’s Five-Minute Veterinary Consult  
OObesity
  BASICS
Obesity is the unhealthy accumulation of body 
fat. Precise definitions are debated but it is widely 
accepted that dogs or cats with body condition 
score (BCS) 6 or 7 on a 9-point scale are over  - 
weight, and those with BCS 8 or 9 are obese.
• Animals gain weight when energy intake 
from food chronically exceeds energy expended 
to maintain basic homeostatic processes and 
during exercise. • Homeostatic neuroendocrine 
responses ensure food intake meets energy 
requirements and establish modest energy 
reserves in case of a period of fasting. • Energy 
homeostasis may be disrupted by: ready 
availability of highly palatable energy-dense 
food (which elicits hedonic responses that 
override homeostatic satiation); genetic 
variation in appetite; neutering; and limits to a 
pet’s ability to exercise.
• Endocrine—insulin resistance develops 
secondary to obesity and can lead to diabetes 
mellitus in cats. • Immune—adipose tissue 
dysfunction in obesity causes a proinflammatory 
state. • Other organ systems may be affected by 
the mechanical effect of increased body fat and/
or endocrine and metabolic disruption.
GENETICS
• Breed variation in obesity predisposition 
suggests obesity susceptibility is in part 
heritable with a polygenic mode of inheritance. 
• Mutations in the genes POMC  (Labrador 
and flatcoat retrievers) and MC4R  (beagles) are 
associated with obesity and/or food motivation.
Common. As many as 65% of dogs and 25% 
cats are overweight or obese.
Species
• Domestic shorthair cats. • Labrador 
retriever, Cairn terrier, cavalier King Charles 
spaniel, Scottish terrier, cocker spaniel.
Obesity prevalence is highest in middle age 
but can occur throughout life.
Neutered pets of either sex are predisposed.
SIGNS
• Weight gain. • Change in BCS. • A full 
diet and exercise history and understanding of 
concurrent medical problems is essential to 
formulating a treatment plan.Physical Examination Findings
Excess body fat and BCS (see Diagnostic 
Procedures).
CAUSES
Energy intake chronically exceeding energy 
output.
• Neutering. • Middle age. • Feeding highly 
palatable, energy-dense foods without 
adequate restriction. • Restricted exercise 
(e.g., following injury, indoor cats, or 
leash-only exercise). • High drive for food, 
driven by genetic variation (e.g. Labrador 
retriever POMC  mutation). • Uncommonly, 
endocrinopathies can cause obesity (hypo -
thyroidism, insulinoma), or mimic obesity 
(as with the abdominal enlargement of 
hyperadrenocorticism).
  DIAGNOSIS
Abdominal distention from pregnancy, 
ascites, hyperadrenocorticism, or neoplasia.
Normal or may reflect endocrine disruption 
(hyperglycemia, dyslipidemia) or concurrent 
disease.
N/A
IMAGING
Ultrasound, MRI, or dual-energy x-ray 
absorptiometry can measure body fat more 
accurately.
• BCS is a semi-quantitative, ordinal 
measure of body composition. Observation 
and palpation are used to assign a score 
based on how findings best match a series of 
descriptors. The best validated 9-point scale 
assigns BCS 4–5 as ideal, 6–7 as overweight, 
and 8–9 as obese. • Serial measurement of 
body weight is more sensitive for 
N/A
  TREATMENT
• Outpatient. • Calorie restriction is the 
mainstay of successful weight loss. • Changes 
in owner management behavior are critical to 
success. • Energy requirements for 
maintenance are lower after weight loss so 
long-term vigilance and food restriction are 
required to prevent recurrence.
N/AACTIVITY
• Increasing exercise is ineffective to induce 
weight loss alone so if owners are reluctant to 
make management changes, focus should be 
on food restriction. • However, exercise is 
encouraged because it promotes retention of 
lean mass (muscle) during weight loss.
DIET
• Reducing daily energy intake in food to 
below maintenance requirements is essential. 
• Target weight is estimated from current 
weight and BCS—every 1 unit increase over 
BCS 5/9 equates to 10% excess body mass; 
e.g., to calculate the target weight of a dog in 
BCS 7, divide current weight by 1.2. • The 
amount of food required to promote weight 
loss can be estimated from calculated 
maintenance energy requirements (MER) or 
by reducing current food intake by 10–20%. 
• To calculate MER, use estimated target 
weight (MER (kJ) = 440 × body weight 
[BW]kg0.75) and feed 50–65% of MER as a 
starting point. • Feeding recommendations 
should be altered from baseline to maintain 
weight loss at 0.5–1% per week until target 
weight is reached. • For weight loss of <20% 
(i.e., starting BCS <6), food restriction is 
moderate and a conventional diet is adequate, 
although specialized diets may be advant -
ageous. Where energy restriction is greater 
(starting BCS >7), the density of essential 
nutrients in maintenance diets may be 
inadequate so a specialized diet is recom -
mended. • Specialized diets improve the 
success of weight loss programs and improve 
satiety, which itself may improve compliance 
because owners are subjected to less begging 
behavior. • Specialized diets are commonly 
formulated to provide: high essential nutrient 
density; low energy density (added water in 
canned food or air in kibble); high protein 
(improves satiety and promotes lean mass 
retention); and high fiber (promotes satiety). 
Canned (compared to dry) food may improve 
weight loss in cats. • Accurate feeding using 
weighed portions is important. T reats are 
ideally excluded but if owners feel they are 
essential, factor them into the diet plan.
• Owners of obese pets often do not follow 
advice to reduce their pets’ weight because they 
do not recognize obesity, do not see it as a 
problem, or struggle to follow the advice. By 
definition, they have already failed to make the 
small adjustments needed to keep their dog 
slim; it follows that they are likely to find 
making the major changes required to reduce 
their dog’s weight difficult. • Although it 
might sound simple to “feed less and exercise 
more,” the reality is that owners are being 
asked to change established habits, spend more 
time caring for their pets, and perhaps work to 
motivate other family members. • Promoting 
those behavior changes requires us to motivate 
owners, to understand their barriers to change, 
and to offer practical and simple advice on

Canine and Feline, Seventh Edition  987
O
how to overcome those barriers. Information 
does not automatically lead to motivation; it is 
more likely if the actions required are 
consistent with their existing values and beliefs. 
• Owners may not recognize obesity. Being 
overweight is regarded as the norm for some 
breeds. Regular recording of body weight and 
BCS can objectively identify a problem early 
(“I see she’s gained a pound—it would be good 
to cut the food down before that becomes a 
problem”). • Owners may not appreciate that 
obesity causes health problems. Positive 
motivation (“slimming him down could really 
improve his mobility”) is more effective than 
negative (“if he doesn’t lose weight he’ll never 
walk properly again”). • Lack of motivation 
may be difficult to modify (“his breeder says 
his weight is fine”) or challenge (“everyone in 
our family carries a little extra weight—it’s 
cuddly”). • Owners often find food restriction 
difficult. Reducing intake in highly food-
motivated animals may require constant 
vigilance to reduce scavenging, stealing, or 
hunting. Ignoring begging requires a strong 
will because of the importance of food-giving 
in maintaining the human–animal bond. 
Owners may not feel confident in how or what 
to feed. Practical problems may limit the 
exercise they offer their pet. • Practical advice 
to overcome those barriers should ideally be 
tailored to each owner. If owners complain 
their pets are always hungry, a satiety-
promoting diet or trickle feeding using toys or 
frequent small meals may help. If owners insist 
on treat feeding, suggest low-calorie treats or 
factor planned treats into the daily ration. If 
owner mobility restricts dog walks, suggest ball 
play or longer time in the yard to increase 
activity. • Human behavior change is also 
improved by goal-setting, action planning, and 
monitoring. For instance, the aim for a weight 
loss consultation could be that owners leave 
with written plans formulated in the session: 
“my goal is to slim her down to 18 kg”; “I have 
chosen to make these 3 management changes 
from the list of suggestions…”; and “I will 
bring her back once a month to be weighed.” 
• Fostering a nonjudgmental and supportive 
veterinary practice culture regarding pet 
obesity should encourage owners to seek 
support and act early.
N/A
No approved medications for use in United 
States or Europe.
N/A
N/APOSSIBLE INTERACTIONS
N/A
N/A
  FOLLOW-UP
• Monitoring progress is important. After 
initiating a diet change, check progress after 2 
weeks and alter food ration to aim for 
0.5–1% body weight loss per week. Regular 
monthly visits promote owner compliance 
and allow ration changes to maintain 
progress. • Once target weight is achieved, 
ongoing monitoring is essential to minimize 
rebound weight gain. Weighing at veterinary 
visits is ideally supplemented by owners 
becoming more adept at noticing weight gain 
and acting to reverse it.
• Prevention should be a central aim of 
routine vet visits. Veterinary teams should 
work to empower owners to recognize a 
healthy weight and to intervene effectively 
when obesity occurs. • Weight and BCS 
should be recorded at every practice visit. 
• Incorporating weight management advice 
into waiting room displays will establish the 
importance of maintaining a healthy weight 
to the client population.
See Associated Conditions.
• Food restriction leads to weight loss in 
research settings but in client-owned dogs has 
lower success rates. Compliance is frequently 
poor and total weight loss often falls short of 
the target. Rebound weight gain is common. 
• Encouragingly, however, even modest 
weight loss (of approximately 10%) can 
produce clinically significant improvement.
• Dyslipidemia.* • Insulin resistance (dogs 
and cats), diabetes mellitus (cats).* • Hepatic 
lipidosis (cats).* • Hypothyroidism.** 
• Insulinoma.**
Orthopedic
• Osteoarthritis. • Humeral condylar 
fractures. • Cranial cruciate ligament rupture. 
Cardiorespiratory Disease
• T racheal collapse.* • Brachycephalic 
obstructive airway syndrome.* • Laryngeal 
paralysis.* • Increased blood pressure.*Urogenital System
• Urethral sphincter mechanism incompetence.* 
• Feline lower urinary tract disease.* • Dystocia.*
Neoplasia
• General incidence and specifically 
mammary neoplasia and transitional cell 
carcinoma.*
Other
• Heat intolerance/heat stroke.*
• Increased anesthetic risk.*
• Decreased lifespan.*
*Conditions where obesity is proven or 
implicated in causing or exacerbating disease. 
**Conditions implicated in causing obesity. 
Where unspecified, obesity association is 
likely to be both cause and effect or is 
unknown.
Obesity is most common in middle-aged dogs 
and middle-aged to old cats.
N/A
Obesity is associated with reduced fertility 
and dystocia. Food restriction is 
contraindicated during pregnancy.
SYNONYMS
Overweight
SEE ALSO
Diabetes Mellitus.
• BCS = body condition score.
• MER = maintenance energy requirement .
• https://www.wsava.org/nutrition-toolkit
• https://petnutritionalliance.org/
Flanagan J, Bissot T, Hours M-A, et al. Success 
of a weight loss plan for overweight dogs: the 
results of an international weight loss study. 
PLoS ONE 2017, 12(9):e0184199.
Laflamme DP . Development and validation 
of a body condition score system for cats: a 
clinical tool. Feline Pract 1997, 25:13–18.
Laflamme DP . Development and validation of 
a body condition score system for dogs: a 
clinical tool. Canine Pract 1997, 22:10–15.
Linder DE, Parker VJ. Dietary aspects of 
weight management in cats and dogs. Vet 
Clin North Am Small Anim Pract 2016, 
46:869–882.
Raffan E, Dennis RJ, O’Donovan CJ, et al. A 
deletion in the canine POMC gene is 
associated with weight and appetite in 
obesity-prone Labrador retriever dogs. Cell 
Metab 2016, 23(5):893–900.
Author  Eleanor Raffan
available online(continued)  Obesity

988  Blackwell’s Five-Minute Veterinary Consult  
OOdontogenic Tumors
  BASICS
OVERVIEW
• Odontogenic tumors are defined by the 
World Health Organization (WHO) as 
“lesions derived from epithelial, ectomesen­
chymal and/or mesenchymal elements that 
still are, or have been, part of the tooth ­
forming apparatus”.
• Epulis  (Greek epi-oulon  meaning “on the 
gum”) is a nonspecific, clinical term used to 
describe tumors and tumor ­like masses of the 
gingiva.
• Odontogenic tumors are categorized into 
three broad groups with specific tumor types 
in each category:
◦ T umors of odontogenic epithelium: 
conventional ameloblastoma; canine 
acanthomatous ameloblastoma; amyloid ­
producing odontogenic tumor.
◦ T umors of odontogenic epithelium 
with odontogenic ectomesenchyme: 
ameloblastic fibroma, ameloblastic 
fibro ­dentinoma, and ameloblastic 
fibro ­odontoma; feline inductive 
odontogenic tumor; odontoma.
◦ T umors of mesenchyme and/or odontogenic 
ectomesenchyme: peripheral odontogenic 
fibroma; feline “epulides”; odontogenic 
myxoma/myxofibroma.
We focus here on the most common 
odontogenic tumors:
• Conventional ameloblastoma (CA):
◦ Benign but expansile, locular to multilocular 
tumor of the jaws in dogs and cats.
◦ Differs in biological behavior from the 
more common CAA.
• Canine acanthomatous ameloblastoma (CAA):
◦ Benign but invasive tumor of the jaws.
◦ Typically more invasive than expansile.
◦ No apparent human analogue.
• Amyloid ­producing odontogenic tumor 
(APOT):
◦ Benign but expansile tumor of the jaws 
affecting primarily dogs.
◦ Similar biological behavior to the CA 
with a propensity to produce amyloid.
• Feline inductive odontogenic tumor (FIOT):
◦ Benign odontogenic tumor unique to cats.
◦ Generally expansile and locular with 
epicenter at an impacted and/or malformed 
maxillary canine tooth.
• Peripheral odontogenic fibroma (POF):
◦ Benign tumor primarily composed of 
periodontal ligament ­like stroma arising 
from tissue near the alveolar margin.
◦ Current debate as to whether this is a 
tumor or a reactive lesion.
• Feline “epulides”:
◦ Clinically presents as a typical epulis.
◦ Not clear whether this lesion is analogous 
to POF of dogs.◦ Most cats are presented with multifocal 
lesions distributed throughout the entire 
oral cavity.
• Dog—odontogenic tumors are generally 
considered uncommon but CAA has been 
reported to be the fourth most common oral 
tumor in dogs. POF may be even more 
common.
• Cat—odontogenic tumors are rare in cats.
• CAA is more common in golden retrievers 
and possibly cocker spaniels.
• Boxers may have higher incidence of POF .
SIGNS
• Often minimal—incidental finding 
detected on routine physical examination.
• If severe—excessive salivation, halitosis, 
dysphagia, bloody oral discharge, weight loss.
• Oral mass—in early cases, may appear as 
small, pedunculated masses.
• Displacement of tooth structures due to the 
expansile nature of the mass.
• Possible facial deformity due to asymmetry 
of the maxilla or mandible.
• Occasionally cervical lymphadenopathy.
• CA—generally an intraosseous cystic lesion 
with osseous expansion.
• CAA—generally an extraosseous lesion with 
an irregular surface that arises within the 
gingiva; more common in rostral mandible.
• APOT—generally an expansile mass, 
similar to the CA; when the amyloid deposits 
become mineralized a mixed radiolucent–
radiopaque appearance may be seen.
• FIOT—a central tumor typically presenting 
as a large swelling of the rostral maxilla in 
young cats.
• POF—typically a firm, sessile to 
pedunculated, nonulcerated lesion that is 
most often associated with the free gingiva. 
Infrequently seen primarily as a broad ­based 
mass in the attached gingiva.
• Feline “epulides”—most cats present with 
multifocal lesions distributed throughout the 
entire oral cavity.
  DIAGNOSIS
• Benign oral tumor.
• Malignant oral tumor.
• Focal fibrous hyperplasia.
• Pyogenic granuloma.
• Gingival hyperplasia/enlargement.
• Differentiated from other types of masses 
by incisional biopsy coupled with radio­
graphic appearance.CBC/BIOCHEMISTRY/URINALYSIS
Results usually normal.
Cytologic preparations are rarely diagnostic.
IMAGING
• Determine tumor borders by CT or 
intraoral radiographs.
• Radiographs of CA, APOT and FIOT 
typically demonstrate significant expansion 
with loculated appearance; APOT may 
exhibit mixed radiopacity due to minerali­
zation of amyloid; CAA is typically infiltrative 
into bone; POF and feline “epulides” 
generally do not invade bone but can displace 
tooth structures and may have ossified 
• CT scan is best modality for surgical planning.
A large, deep tissue biopsy (down to and 
including bone) is required to definitively 
diagnose.
  TREATMENT
• Ameloblastomas and APOT—complete 
surgical excision is realistic and prognosis with 
clean margins is good to excellent, making wide 
surgical excision the treatment of choice. 
Radiation therapy has been utilized in dogs and 
cats with variable results. CA is located primarily 
within bone and is, as such, more radioresistant.
• POF—POFs arise from periodontal ­like 
stroma in the gingiva or underlying 
periosteum at or near the cementoenamel 
junction. Local conservative excision of the 
tumor with particular attention paid to 
removing the entire lesion, excising down to 
and including the affected periosteum, should 
be anticipated to be curative. Such an 
approach may, however, require 
reconstruction of the gingiva surrounding the 
remaining tooth. Recurrence is likely if the 
entire lesion is not excised. More aggressive 
treatments may be reserved for recurrent 
lesions or those that have a more regional, 
broad ­based presentation.
• FIOT—similar to most odontogenic 
tumors, no case ­controlled studies have been 
performed to evaluate the appropriate 
treatment for FIOTs. However, similar to 
most odontogenic tumors, it appears that if 
the tumor is surgically resected in its entirety 
(0.5–1 cm intended surgical margins), the 
tumor is unlikely to recur.
• Feline “epulides”—it is clear that surgical 
management of feline epulides, while 
recommended, is not as straightforward as is 
the case with canine POF . This is because 
most cats are presented with multifocal 
lesions, making local surgical excision alone

Canine and Feline, Seventh Edition  989
O
challenging. Recurrence with such a 
conservative approach is likely and some cases 
require multiple extractions and gingivectomy 
to achieve complete resolution.
• Efficacy of outpatient chemotherapy is 
unreported; most tumors of mesenchymal 
origin respond poorly.
• Intralesional bleomycin has been reported 
for CAA.
  FOLLOW-UP
• Thorough oral, head, and neck examination 
regularly after treatment.
• Medical surveillance with CT or intraoral 
radiographs every 3–6 months.EXPECTED COURSE AND PROGNOSIS
• CA, CAA, APOT, and FIOT are highly 
invasive/expansile in bone.
• No known metastasis.
• Good to excellent prognosis/surgical cure 
can be expected when excisional margins are 
free of neoplastic cells.
• Mean survival after radiotherapy in dogs 
with CAA ranges from 1 to 102 months 
(median, 37 months); 1 ­year survival rate 
85%; 2 ­year survival rate 67%.
• APOT = amyloid ­producing odontogenic 
tumor.
• CA = conventional ameloblastoma.
• CAA = canine acanthomatous ameloblastoma.
• FIOT = feline inductive odontogenic tumor.
• POF = peripheral odontogenic fibroma.
https://avdc.org/avdc ­nomenclature/ Suggested Reading
Ultrasound 2014, 55:147–158.
Fiani N, Verstraete FMJ, Kass PH, Cos DP . 
Clinicopathological characterization of 
JW. Clinical characterization of canine 
263 dogs and the influence of postsurgical 
histopathological margins on local 
Thrall DE. Orthovoltage radiotherapy of 
acanthomatous epulis in 39 dogs. J Am Vet 
Med Assoc 1984, 184:826–829.
Author  Jason W. Soukup
Consulting Editor  Heidi B. Lobprise(continued)  Odontogenic Tumors

990  Blackwell’s Five-Minute Veterinary Consult  
OOdontoma
  BASICS
OVERVIEW
• Odontoma—oral mass that arises from 
odontogenic epithelial and mesenchymal origin:
◦ Ameloblastic fibro-odontoma (AFO) 
(formerly ameloblastic odontoma)—
radiolucent, mass with osteolysis and varying 
amounts of intralesional mineralization.
◦ Complex odontoma—radiodense mass 
with fully differentiated dental components 
(more organized than AFO), but unorganized  
at the cellular level with no tooth-like 
◦ Compound odontoma—mass with fully 
differentiated dental components resulting 
in the presence of denticles (tooth-like 
structures).
• Hamartoma—proliferation of normal 
cellular components with an abnormal 
organization; not a true neoplasm (applicable 
to complex and compound odontoma types).
◦ A definition to help delineate the three 
types of odontoma, not a type in itself.
Typically found in young animals.
SIGNS
• Oral swelling or mass.
• Delayed deciduous tooth exfoliation or 
delayed or abnormal tooth eruption at site.
• AFO:
◦ Most lesions are radiolucent with single or 
multiple (multilocular) expansile lesions of 
irregular configurations of dental components.
◦ Some lesions are associated with 
impacted teeth.
◦ Neoplastic mechanism, may recur (World 
Health Organization [WHO]—benign 
neoplasm).
• Complex:
◦ Disorganized tissues within a thin, 
fibrous capsule.
◦ Radiographically, often a radial structure 
of hard tissue particles inside a radiolucent 
zone, embedded in the maxilla or mandible.
◦ Erupted teeth in that area may allow for 
communication between the odontoma and 
oral cavity, with a potential for bacterial 
contamination and infection.
• Compound:
◦ The presence of denticles is patho  - 
gnomonic.
◦ Small, rudimentary teeth with crown 
formed, but the roots are often misshapen 
(dilacerated).
◦ Denticles often associated with 
radiolucency.
◦ May be embedded or have some extent of 
eruption.CAUSES & RISK FACTORS
AFO
• Mixed odontogenic tumor with 
differentiation of odontoblasts, ameloblasts 
and cementoblasts embedded in cellular 
mesenchymal tissue.
• Reciprocal inductive interaction of 
epithelial and mesenchymal tissues.
• WHO classification as a benign neoplasm 
with possible reoccurrence.
Complex Odontoma
Inductive processes resulting in dental 
components but not fully organized.
Compound Odontoma
Differentiation of dental components into 
varying levels of organization—denticles.
  DIAGNOSIS
• Other oral masses:
◦ Ameloblastic fibroma—similar to AFO 
but would contain no hard tissue.
◦ Calcifying epithelial odontogenic tumor 
(CEOT)—osteolysis but no mineralization 
or dental (mesenchymal) aspect; slow, not 
inductive, noninvasive.
◦ Amyloid producing odontogenic tumor 
(APOT)—similar to CEOT, but amyloid 
producing; shares biologic features with 
◦ Peripheral odontoma (4 human cases 
diagnosed)—develops in gingiva or alveolar 
mucosa with no attachment to bone; 
associated with impacted or retained teeth; 
similar to erupted odontoma.
Typically not affected.
IMAGING
• Intraoral radiography.
• Advanced imaging typically not 
• Complete oral examination.
  TREATMENT
• Appropriate antimicrobial and pain 
management therapy when indicated.
support during anesthetic procedures.• AFO:
◦ More aggressive excision may be 
necessary due to neoplastic classification; 
consider obtaining a 1 cm surgical margin.
◦ Monitor for local recurrence.
• Complex and compound odontoma:
◦ Enucleation and intracapsular excision 
with aggressive debridement of cyst; more 
aggressive surgical excision can decrease the 
chance of recurrence.
◦ No chemotherapeutic regimens recommended.
◦ Rarely radiotherapy may be beneficial by 
treating microscopically recurring disease.
  FOLLOW-UP
Typical postoperative—pain management, 
Recurrence, local infection, fragile jaw 
• AFO—fair to guarded prognosis, as there is 
a chance of recurrence.
• Complex and compound odontoma—
short- and long-term prognosis good with 
adequate therapy.
• AFO = ameloblastic fibro-odontoma.
• APOT = amyloid-producing odontogenic 
tumor.
• CEOT = calcifying epithelial odontogenic 
tumor.
• WHO = World Health Organization.
Felizzola CR, Martins MT, Stopiglia A, et al. 
Compound odontoma in three dogs. J Vet 
Dent 2003, 20(2):79.
Sowers J, Gengler W. Diagnosis and 
treatment of maxillary compound 
odontoma. J Vet Dent 2005, 21(1):26.
Walker KS, Lewis JR, Durham AC, Reiter 
AM. Diagnostic imaging in dental practice. 
Odontoma and impacted premolar. J Am 
Vet Med Assoc 2009, 235(11):1279–1281.
Author  Matthew S. Lemmons

Canine and Feline, Seventh Edition  991
O
Oliguria and Anuria
  BASICS
• Oliguria—production of an abnormally 
small amount of urine. Several proposed 
definitions; in hydrated patients with good 
perfusion, urine output (UOP) <1.0 mL/
kg/h = absolute oliguria. Acute kidney injury 
(AKI) is typically polyuric, where UOP 
>2 mL/kg/h is expected.
• Anuria—limited/no urine formation (UOP 
<0.08 mL/kg/h).
• Physiologic (prerenal) oliguria—kidneys 
limit water loss during state of reduced renal 
perfusion to preserve fluid and electrolyte 
balance. High plasma osmolality or low 
circulating fluid volume stimulate antidiuretic 
hormone (ADH) synthesis and release, which 
induces formation of small quantity of 
• Pathologic (renal) oliguria—severe renal 
parenchymal impairment. Factors include: 
high resistance in afferent glomerular vessels, 
low glomerular permeability, back leak of 
filtrate from damaged renal tubules, renal 
intratubular obstruction, and extensive loss of 
nephrons resulting in marked reduction of 
glomerular filtrate produced.
• Anuria—may be renal or postrenal origin. 
Severe renal disease occasionally causes 
anuria. Mechanisms are the same as for 
pathologic oliguria (e.g., urinary tract 
obstruction (UTO) or excretory pathway 
rupture).
• Renal—inability to adequately eliminate 
wastes and water; hyperkalemia.
• Urologic—obstruction-induced distension 
of the collecting system. Increased risk of 
urinary tract infection (UTI) due to failure to 
empty bladder.
• Young adult cats—higher incidence of 
anuria associated with UTO.
SIGNS
• Reduction in quantity of urine voided.
• Enlarged urinary bladder, stranguria, 
pollakiuria with urethral obstruction.
• Systemic signs of uremia if oliguria/anuria 
persists.
CAUSES
• Physiologic oliguria—renal hypoperfusion 
or serum hyperosmolality.
• Pathologic oliguria—AKI or advanced 
chronic kidney disease (CKD).
• Anuria—complete UTO, urinary tract 
rupture, or severe primary kidney disease.RISK FACTORS
• Physiologic oliguria—dehydration, 
decreased cardiac output, hypotension.
• Pathologic oliguria and anuria—primary 
kidney disease, nephrotoxin exposure, 
dehydration, low cardiac output, hypotension, 
electrolyte imbalance, acidosis, fever, sepsis, 
liver disease, multiple organ failure, trauma, 
hypoalbuminemia, hyperviscosity syndrome.
• Anuria—caused by urolithiasis, urinary 
tract neoplasia, idiopathic feline lower urinary 
tract disease, functional micturition disorder, 
trauma, gross hematuria.
  DIAGNOSIS
• Physiologic oliguria—poor tissue perfusion, 
history of recent fluid loss, signs of uremia are 
typically absent. Oliguria resolves rapidly 
when renal hypoperfusion is corrected.
• Pathologic oliguria—caused by CKD have a 
history of progressive kidney disease (polyuria, 
polydipsia, poor appetite, weight loss). Patients 
with CKD are at risk for AKI. Signs of uremia 
are commonly observed; fluid therapy and 
other measures to restore adequate renal 
perfusion often fail to increase urine flow.
• Suspect anuria due to UTO or rupture of 
the excretory pathway with repeated 
stranguria and inability to produce urine. 
Patients may have a history of pollakiuria, 
dysuria, hematuria, urolithiasis, trauma, 
instrumentation of the urinary tract. Physical 
exam may reveal enlarged urinary bladder, 
painful posterior abdomen, masses or uroliths 
in the urethra or bladder. Patients with 
rupture of the urinary tract may have ascites, 
fluid infiltration in tissues, painful caudal 
abdomen, masses or uroliths in the bladder or 
urethra, or evidence of trauma. UTO caused 
by functional urinary obstruction: suspect in 
patients with urinary bladder enlargement, 
increased resistance to manual bladder 
expression, and neurologic signs affecting the 
hind limbs and/or tail. Signs of uremia may 
develop. Restoring urinary flow/correcting 
rents in the excretory pathway rapidly restores 
adequate urine flow.
• Serum urea nitrogen, creatinine 
concentration—elevated unless onset of 
oliguria or anuria is very recent.
• Hyperkalemia—common with pathologic 
oliguria and anuria, less common/less severe 
in animals with physiologic oliguria (except 
with hypoadrenocorticism).
• Physiologic oliguria—characterized by high 
urine specific gravity (USG) (dogs >1.030, 
cats >1.035). Oliguria associated with lower 
USG suggests renal parenchymal disease or 
UTO. Patients with urine concentrating 
defects due to other diseases or drugs are the exception to this rule.
• Renal parenchymal anuria is typically 
characterized by USG <1.030 (dogs) or 
<1.035 (cats). USG varies in patients with 
post-renal anuria. Adequate urine-
concentrating ability often lost after UTO.
IMAGING
• Abdominal radiographs and ultrasound are 
useful to rule out UTO/excretory pathway 
rupture.
• Excretory urography, retrograde urethro -
cystography, pyelography, or vaginourethro -
cystography may provide definitive proof of 
UTO/excretory pathway rupture.
• Distension of the excretory pathway or 
detection of uroliths in the ureters, bladder 
neck, urethra suggest UTO.
• Detection of fluid within the peritoneum 
supports a diagnosis of excretory pathway 
rupture. Contrast media leakage confirms a 
rupture.
• Electrocardiography—to identify significant 
arrhythmia (see Hyperkalemia).
• Urethrocystoscopy—may provide evidence 
for UTO/urinary tract rupture.
• Urinary catheterization—may provide 
information about the integrity of the lower 
urinary tract. Not recommended as a 
diagnostic procedure because it may be 
misleading and may cause additional trauma; 
iatrogenic UTI.
  TREATMENT
• Oliguria and anuria are emergencies. Untreated, 
may lead to death within hours to days from 
uremia, hyperkalemia, acidosis, sepsis.
• Persistent hypovolemia may lead to ischemic 
renal injury.
• Correct renal hypoperfusion rapidly by 
intravenous administration of balanced 
isotonic crystalloid.
• Therapy for primary renal oliguria/anuria is 
limited to symptomatic, supportive care while 
awaiting spontaneous renal function recovery. 
Elimination of causative factors may slow or 
stop further renal injury (e.g., terminating 
aminoglycoside therapy, correcting hyper -
calcemia, or restoring adequate renal 
perfusion); however, once pathologic oliguria/
anuria has developed, few kidney diseases will 
be amenable to specific treatment 
(exception = leptospirosis).
• Correct postrenal causes for anuria by 
nonsurgical/surgical methods including 
retrogradeurohydropropulsion of uroliths/
urethral plugs; placement of transurethral 
catheters to restore low-pressure urinary flow; 
removal of uroliths, polyps, neoplastic tissue; or 
surgical repair of rents, strictures, malposition 
of kidneys, ureters, bladder, urethra.

992  Blackwell’s Five-Minute Veterinary Consult  
O  MEDICATIONS
• Diuretics—indicated after establishing 
euvolemia in patients with renal oliguria. 
Diuretic-induced UOP facilitates fluid and 
electrolyte therapy and may imply less severe 
• Administration of diuretics before restoring 
adequate renal perfusion is counterproductive 
and may promote renal injury.
• Avoid diuretic-induced dehydration.
• Furosemide 2–4 mg/kg IV—often used 
first in patients with renal oliguria. Urinary 
flow should increase within 1 hour; if not, 
repeat at the same or double dosage. If 
diuresis ensues, administer to sustain diuresis 
(0.25–1 mg/kg/h or 2–4 mg/kg IV q8h). 
Reduction in glomerular filtration rate (GFR) 
may be seen with therapy.
• Mannitol 0.25–1 g/kg IV can be given as a 
10% or 20% solution over 15–20 minutes. 
Urinary flow should increase within 1 hour. 
Do not repeat if diuresis does not ensue; may 
cause excessive volume expansion. If diuresis 
ensues, mannitol may be continued as 
continuous infusion (1–2 mg/kg/h) or 
intermittent IV doses (0.25–0.5 g/kg every 
4–6 hours) to sustain diuresis. Avoid 
mannitol when overhydration, pulmonary 
edema, or congestive heart failure present.
• Fenoldopam 0.1–0.8  μg/kg/min, a selective 
dopamine A1 receptor antagonist, promotes 
diuresis in healthy animals and increases GFR 
in dogs. Evidence of efficacy in animals with 
renal disease is lacking.
Nephrotoxic drugs.
• Administer fluids carefully to patients that 
are persistently oligoanuric to avoid over -
hydration. Do not continue to administer 
fluids to oligoanuric patients after their fluid 
volume deficit has been restored in the 
absence of a plan to prevent development of overhydration. In patients with unresponsive 
renal oliguria, peritoneal dialysis/hemodialysis 
may be required to correct iatrogenic 
fluid-induced volume overexpansion.
• Failure to correct fluid deficits before 
initiating diuretic administration may cause 
further renal hypoperfusion and ischemic 
• Use drugs requiring renal excretion with 
caution.
• Avoid electrolyte solutions containing 
>4 mEq of potassium/L. Some hypokalemic 
patients may require cautious administration 
of higher doses of potassium.
• Dopamine can cause arrhythmias, 
particularly in animals with hyperkalemia. Its 
use is no longer recommended.
Furosemide may promote the nephrotoxicity 
associated with aminoglycoside antibiotics.
  FOLLOW-UP
• UOP—determine early during the course of 
management. When unclear, consider trans -
urethral catheterization to accurately 
determine UOP . Place catheters using aseptic 
technique. Short indwelling time lowers the 
risk of UTI. Properly placed/managed 
indwelling catheters are usually safe for at least 
48 hours. Use a closed, sterile drainage system.
• Creatinine, serum urea nitrogen, and 
potassium concentrations should be 
reevaluated q12–24 hours; patients with 
severe hyperkalemia need more frequent 
• ECG should be performed at appropriate 
intervals to assess cardiac effects of drugs and 
hyperkalemia and to monitor response to 
therapy.
• Avoid nephrotoxic drugs.
• Avoid dehydration and hypoperfusion.POSSIBLE COMPLICATIONS
• Hyperkalemia and arrhythmia.
• Uremia.
• Overhydration.
• Oliguria and anuria are poor prognostic 
signs in AKI or CKD; unless urine outflow 
can be corrected, survival is not expected.
• Anuria associated with UTO is often 
reversible if urethral patency is restored.
SEE ALSO
• Nephrotoxicity, Drug-Induced.
• ADH = antidiuretic hormone.
• AKI = acute kidney injury.
• CKD = chronic kidney disease.
• GFR = glomerular filtration rate.
• UOP = urine output.
• USG = urine specific gravity.
• UTO = urinary tract obstruction.
disease. In: Bartges J, Polzin DJ, eds., 
Ames, IA: Wiley-Blackwell, 2011, pp. 
472–523.
Therapy XIV. St. Louis, MO: Saunders, 
2009, pp. 879–882.
Consulting Editor  J.D. FosterOliguria and Anuria  (continued)

Canine and Feline, Seventh Edition  993
O
Ollulanus Infection
  BASICS
OVERVIEW
• Ollulanus  adult worms are found in 
stomach of cats.
• Infection causes chronic gastritis resulting 
in anorexia, vomiting, weight loss.
• No intermediate hosts required to complete 
lifecycle; transmission is mainly by contact 
with vomitus of infected cats.
• Eggs develop into larvae within female 
worm; released larvae may mature to adults 
without leaving stomach.
• Colony cats—predisposed, probably 
because of access to other cats’ vomitus.
• Stray cats living in urban areas heavily 
populated with cats—high incidence of 
• Captive cheetahs, lions, tigers, cougars— 
SIGNS
• Chronic vomiting, anorexia, weight loss.
• Death from chronic gastritis.
• Ollulanus tricuspis —adults (only up to 
1 mm in length) coil into gastric mucosa, 
causing superficial erosions.
• Over time, gastric erosions can become 
severe with marked inflammation, 
accumulation of lymphoid aggregates, and 
fibrous changes in mucosa and submucosa.
• Eggs—hatch within female worms; larvae 
develop to infective L3 larvae within stomach.
• L3 larvae and adults—vomited and infective 
to other cats; internal autoinfection also occurs.
• No fecal transmission known.
• Distributed throughout North America, 
Australia, New Zealand, Europe, Argentina, 
Chile.
  DIAGNOSIS
Other causes of vomiting including:
• Dietary.
• Intoxications.
• Metabolic—diabetes mellitus, renal disease, 
liver disease, acidosis, heat stroke, hypo­
adrenocorticism, hyperthyroidism.
• Gastric abnormalities—inflammatory 
bowel disease, neoplasia, obstruction, 
atrophic gastritis, ulcers, dilatation/volvulus, 
parasitic such as Physaloptera .
• Gastroesophageal junction disorders—
hiatal hernia.
• Small intestinal disorders—inflammatory 
bowel disease, neoplasia, fungal, viral, 
obstruction, paralytic ileus.• Large intestinal disorders—colitis, 
obstipation, inflammatory bowel disease.
• Abdominal disorders—pancreatitis, 
gastrinoma, peritonitis, steatitis, pyometra, 
diaphragmatic hernia, other neoplasia.
• Neurologic disorders—psychogenic, 
motion sickness, vestibular lesions, head 
trauma, neoplasia.
• Miscellaneous—heartworm disease and 
Reflects vomiting—dehydration, hypo  ­ 
volemia.
• Baermann—examine vomitus for L3 larvae.
• Fecal examination, direct or flotation—
larvae or eggs seldom found in feces as they 
are digested within the gastrointestinal tract.
IMAGING
Abdominal ultrasound—may show gastric 
thickening; rarely see parasites.
• View worms through an endoscope—
difficult due to size of worms.
• Gastric lavage—using saline collection 
followed by centrifugation to precipitate L3 
larvae, or use Baermann technique.
• Histopathology—gastric biopsy 
occasionally shows parasites.
  TREATMENT
Anthelmintic use is extra ­label and anecdotal.
• Fenbendazole 50 mg/kg PO q24h for 5 days, 
oxfendazole 10 mg/kg q24h for 5 days, and 
pyrantel pamoate 10 mg/kg PO q24h for 3 days 
are recommended but there is little information 
available regarding treatment success.
• Tetramisole—give as a 2.5% formulation at 
5 mg/kg PO once; effective but not available 
in the United States.
Tetramisole—at this dose should not cause 
any side effects in cats.
  FOLLOW-UP
Warn owner to watch for further vomiting—
retreatment may be required.  MISCELLANEOUS
Ollulanus  infection has been identified in a 
cat with concurrent gastric adenocarcinoma.
Barr SC, Bowman DD. Ollulanus  infection. 
In: Canine and Feline Infectious Diseases 
and Parasitology. Ames, IA: Blackwell, 
2006, pp. 385–387.
et al. Ollulanus tricuspis . In: Feline Clinical 
Parasitology. Ames, IA: Iowa State 
University Press, 2002, pp. 262–265.
Cecchi R, Wills SJ, Dean R, et al. 
Demonstration of Ollulanus tricuspis  in the 
stomach of domestic cats by biopsy. J Comp 
Pathol 2006, 134:374–377.
Dennis MM, Bennett N, Ehrhart EJ. Gastric 
adenocarcinoma and chronic gastritis in two 
related Persian cats. Vet Pathol 2006, 
43:358–362.

994  Blackwell’s Five-Minute Veterinary Consult  
O  BASICS
OVERVIEW
• Infection of the conjunctiva and/or cornea 
before or just after the separation of the 
eyelids in the neonate.
• Occurs in puppies and kittens.
• Associated with Staphylococcus  spp. or 
Streptococcus  spp. in dogs and cats, and with 
herpesvirus in cats.
• Potentially vision threatening.
• Source of infection—believed to be from an 
intrauterine infection, a vaginal infection of 
the dam at the time of birth, or from a 
nonhygienic environment.
• Affects all breeds of cats and dogs.
• Neonates before the time that the eyelids 
open (10–14 days postpartum).
SIGNS
• Upper and lower eyelid margins are fused 
(physiologic ankyloblepharon) and lids bulge 
outward because of the accumulation of 
debris and discharge within the conjunctival 
sac (Figure 1).
• Mucous to mucopurulent discharge may 
extrude through a patent opening at the 
• Cornea and conjunctiva may be ulcerated.
• May note adhesions (symblepharon) of the 
conjunctiva to the cornea or to other areas of 
the conjunctiva (including that of the nictitans).
• Perforation of the cornea with iris prolapse 
and collapse of the globe is occasionally seen.CAUSES & RISK FACTORS
• Intrauterine or vaginal infections in the 
dam near the time of birth.
• Unclean environment for the neonates.
  DIAGNOSIS
Neonates with entropion in which the eyelids 
have already separated—mucus to mucopurulent 
discharge may be present; view of the cornea 
may be obscured; may have appearance of 
ankyloblepharon; differentiated by age 
(patients older than 10–14 days) and ability 
to separate the eyelids.
Normal unless there is a concurrent systemic 
• Cultures of neonate’s ocular discharge and/
or dam’s vaginal discharge—may help 
diagnose bacterial infection and guide 
antibacterial therapy.
• Cytology of the affected tissues—may help 
• Immunofluorescent antibody or PCR tests 
(cats)—feline herpesvirus.
IMAGING
N/A
• Full physical examination of the dam and 
neonate.• Fluorescein staining—corneal or 
conjunctival ulceration.
  TREATMENT
• Separation of the eyelids—cornerstone 
of treatment; can be accomplished by 
careful massage and manual traction 
beginning at the medial canthus or 
introduction of a closed hemostat, small 
blunt scissor blade or the blunt, butt end 
of a scalpel blade into the patent opening 
or groove of the future lid fissure at the 
medial canthus and gently separating (not 
cutting) the eyelids.
• Lavage of conjunctival sac and cornea with 
warm saline or a 1:50 diluted povidone–
iodine aqueous solution to remove the 
• Warm compresses may aid in separating the 
eyelids and preventing readherence.
• Systemic support as needed.
• Broad-spectrum, topical antibiotics—e.g., 
neomycin/bacitracin/polymyxin B; applied 
4 times daily for at least 1 week; antibiotic 
chosen on basis of bacterial culture and 
sensitivity, if available.
• Antiviral therapy in the case of herpesvirus 
infection in cats.Ophthalmia Neonatorum
Figure 1 .
Ophthalmia neonatorum. Typical outward-bulging lids due to accumulation of debris and discharge 
within the conjunctival sac. Source: Ophthalmology Section, Vetsuisse Faculty, University of Zurich.

Canine and Feline, Seventh Edition  995
O
• Tetracyclines—do not use in neonates 
because of the risk of affecting bone or teeth; 
topical ofloxacin or ciprofloxacin is drug of 
choice for Chlamydophila .
• Topical corticosteroids—contraindicated.
  FOLLOW-UP
• Warm compresses—may be necessary for a 
few days to keep the eyelids from readhering.
• Topical antibiotics—continued for a 
minimum of 7 days.• Observe littermates that are not initially 
affected.
• T reat vaginal infections in the dam with 
appropriate medications.
• Keep the external environment and the 
dam’s nipples clean.
• T reat vaginal infection in the dam before 
delivery, if possible.
• Severe keratitis with scarring and 
symblepharon.
• Rupture of the cornea with secondary 
phthisis; blindness may be irreversible.EXPECTED COURSE AND PROGNOSIS
Favorable with correct and timely diagnosis and 
treatment and if no major complications occur.
Blackwell, 2013, pp. 832–893.
Consulting Editor  Kathern E. Myrna(continued)  Ophthalmia Neonatorum

996  Blackwell’s Five-Minute Veterinary Consult  
OOpiates/Opioids Toxicosis
  BASICS
• Opiates are derived from opium; opioids 
are synthetic.
• Opium was initially obtained from unripe seed 
capsules of the Papaver somniferum  (poppy 
plant). Raw opium powder contains 24 alkaloids 
including ~10% morphine, 0.5% codeine, and 
thebaine (codeine methyl enol ether).
• Opioids have been used for millennia, but 
human use and abuse of opioids has 
drastically increased the last several years and 
has been increasing overall for the prior 20 
years. This corresponds to an increase in 
accidental canine oral exposures.
• In dogs, opioids generally act as CNS, 
respiratory, and cardiovascular depressants, 
however thebaine has stimulatory properties.
• In cats, CNS stimulation often occurs 
following opioid toxicosis.
• Range of opioids and opiates includes:
◦ Agonists—morphine, codeine, 
hydromorphone, oxycodone, fentanyl, 
heroin, desomorphine, alfentanil, tramadol 
(also a serotonin reuptake inhibitor), 
loperamide (relatively low concentrations 
achieved in the CNS).
◦ Partial agonists or agonists/antagonists—
butorphanol, buprenorphine.
• Toxic dose is highly variable depending on 
specific opioid. Cats have an increased 
susceptibility to morphine due to the lack of 
glucuronyl transferase and therefore 
glucuronidation.
• Opioids are weakly acidic and well 
absorbed by oral and transmucosal route.
• Significant hepatic metabolism and first 
pass effect.
• Oral exposure to cut or chewed 
transdermal patches can result in increased 
and rapid absorption compared to that of 
the intended transdermal route. The 
amount of fentanyl remaining in used 
patches is highly variable and can be 
between 28 and 84%.
• Opioid receptors are found in the CNS, 
autonomic nervous system (ANS), gastro­
intestinal (GI) tract, heart, kidney, adipocytes, 
lymphocytes, vas deferens, and adrenal gland. 
The receptor types present and the clinical 
significance in toxicosis varies widely between 
tissue type.
• Major opioid receptors include:
◦ mu—2 specific types. Agonist stimulation 
of mu1 results in supraspinal analgesia while 
mu2 results in spinal analgesia, respiratory 
suppression and decreased GI motility.
◦ delta—equivocal role; possibly potentiates 
mu receptor agonists or has increased 
selectivity for enkephalins compared to mu receptors. Results in spinal analgesia and 
possibly decreased GI motility, decreased 
cardiovascular function, and altered behavior.
◦ kappa—agonist stimulation results in 
analgesia, sedation, and dysphoria.
◦ sigma—does not mediate analgesia significantly; 
no longer classified as an opioid receptor.
• Minor receptors include: epsilon and zeta.
hypoxia, apnea.
• Cardiovascular—bradycardia, hypotension, 
cardiovascular collapse, vasodilation, hyper ­ 
tension.
• Nervous—dog: CNS depression, ataxia, 
seizures, coma; cat: CNS stimulation, 
aggression, vocalization, ataxia.
• Gastrointestinal—vomiting, hypersali­
vation, ileus, constipation.
• Behavioral—aggression.
• Ophthalmic—miosis initially; mydriasis 
more commonly in cats and in dogs if 
hypoxia occurs.
• Hemic/lymphatic/immune—immune 
suppression reported in humans and potential 
in canines/felines with chronic exposures.
• Other—hypothermia, hyperthermia.
GENETICS
Dogs with the MDR1 /ABCB1  genetic 
mutation have an increased sensitivity to 
loperamide. Clinical signs may occur at 
approximately 0.06 mg/kg, compared to 
0.65 mg/kg in dogs with no mutation.
• Opioid exposures are underreported by 
animal owners due to stigma and fear of law 
enforcement.
• Increased incidence of exposure among 
police or narcotic working dogs.
N/A
Species
Collies, and other breeds prone to the 
MDR1 /ABCB1  gene mutation have a greater 
sensitivity to loperamide.
Increased risk of exposure with puppies and 
younger adult dogs due to general increased 
incidence of dietary indiscretions.
SIGNS
• Dogs—analgesia, lethargy, ataxia, 
hypotension, bradycardia, arrhythmia, 
bradypnea, vomiting, ileus, early excitation 
and tachypnea, hypothermia, miosis, hyper­
salivation, defecation, cyanosis, coma.
• Cats—analgesia, CNS excitation, 
aggression, depression, hypotension, 
arrhythmia, seizures, mydriasis, ileus, bradypnea (tachypnea possible early), 
hypothermia, miosis, hyperthermia.
CAUSES
• Primarily dietary indiscretion of 
prescription medications or illicit opioids.
• Other possible exposures include iatrogenic 
exposure, malicious intent, and severe 
exposures in dogs that have been used to 
transport drugs illicitly (“pack dogs” or “mule 
dogs”) where the packages have ruptured 
while inside the dog.
• Access to opioids/opiates.
• Police or narcotic working dogs.
  DIAGNOSIS
• Depressants—other possible intoxicants 
including benzodiazepines, barbiturates, 
marijuana/tetrahydrocannabinol (THC), 
rodenticide (bromethalin), ivermectin, 
alcohol, ethylene glycol, xylitol; trauma; 
infection (encephalitis); other causes of 
encephalopathy or hypoglycemia.
• Stimulants—amphetamines and 
amphetamine ­like medications/drugs, 
cocaine, caffeine, metaldehyde, strychnine.
No alterations expected directly from opioid 
exposure, though secondary alterations may 
occur depending on presence and degree of 
• Over ­the­counter urine drug tests may have 
positive results following an exposure to 
opioids/opiates depending on the specific 
drug, dose ingested, and time frame. Possible 
false positives include rifampin, quinolone 
antibiotics, and poppy seeds.
• Serum or urine gas chromatography–mass 
spectrometry (GC/MS) or liquid chromato­
graphy tandem mass spectrometry (LC/
MS­MS) may be performed, but results are 
unlikely to be available in a timely fashion to 
help guide treatment.
IMAGING
None
None
No specific findings.
  TREATMENT
• Inpatient vs. outpatient medical management 
depends largely on the dose ingested, time

Canine and Feline, Seventh Edition  997
O
frame, and clinical signs. Typically, inpatient 
medical management is recommended with a 
recent ingestion significantly above therapeutic 
doses (if available).
• For inpatient care, monitor for 
development or worsening of clinical signs 
and treat as needed. If there is severe 
respiratory depression, intubation and 
ventilation may be required and may 
necessitate transfer to a referral center 
depending on locally available facilities.
Monitor neurological status, temperature, 
respiratory rate, heart rate/electrocardiogram, 
blood pressure, hydration, and evidence of 
normal GI motility. Correct abnormalities as 
needed.
ACTIVITY
Prevent self ­trauma while the patient has 
CNS depression or agitation.
DIET
Feed normally if the patient can protect their 
airway.
• Minimize potential future exposures.
• Keep medications/drugs out of reach of pets 
and pets away from gatherings where 
exposure is possible.
If packets containing drugs have been surgically 
placed in a “pack dog” or ingested whole by a 
police or narcotic working dog, surgical 
removal of the intact packets is prudent.
• Decontamination:
◦ If asymptomatic, induce emesis in dogs 
within 1–2 hours post ingestion with 
apomorphine (0.03 mg/kg IV) or H2O2 
(1 mL/kg PO first dose, 2 mL/kg (up to 
50 mL) PO second dose if the dog does not 
vomit within 10–15 minutes).  Do not 
induce emesis if there is risk of aspiration.
◦ Gastric lavage may be performed within 
1–2 hours of an ingestion if unable to 
induce emesis due to clinical signs or large 
dose was ingested.
(sorbitol) ×1 dose. Administer activated 
charcoal without a cathartic q6–8h × 2 
additional doses for medications/drugs that undergo enterohepatic recirculation (e.g., 
morphine) or extended release products.
• IV fluids to maintain hydration and 
perfusion; adjust rate as needed based on 
cardiovascular and hydration status.
• Naloxone (reversal agent with a high affinity 
for the mu receptor) 0.01–0.04 mg/kg IV, IM, 
or SQ. Depending on response, may need to 
increase dose (0.1–0.2 mg/kg) to reach an 
effective dose in cats or with opioids such as 
buprenorphine that have a strong mu bonds 
and/or also bind the delta or kappa receptors. 
The duration of action is short (<2–3 hours in 
dogs; <1 hour in cats); redose as needed based 
on recurrence of clinical signs.
• Ileus—metoclopramide 0.1–0.5 mg/kg IM, 
SQ, PO q6h or 1–2 mg/kg/day IV CRI.
• Seizures—diazepam 0.5–1 mg/kg IV or 
phenobarbital 3–10 mg/kg IV to effect.
None
Naloxone is not effective for reversing seizures 
resulting from meperidine, tramadol, or 
propoxyphene toxicosis.
None
Butorphanol 0.05–0.1 mg/kg IV, IM PRN to 
partially reverse pure mu agonists.
  FOLLOW-UP
• Discharge when asymptomatic. No further 
monitoring is expected to be required if severe 
clinical signs such as persistent poor 
perfusion, hyperthermia, seizures did not 
occur.
• If severe signs occurred, secondary renal or 
hepatic elevations are possible (though 
unlikely), and ongoing monitoring is 
recommended as needed based on the clinical 
signs. Acute kidney injury may occur if there 
is prolonged hypotension present; hepatic and 
creatine kinase elevations with persistent 
seizures/hyperthermia.
• Minimize access for ingestion of opioids/
opiates. Additional training, supervision, and 
use of basket muzzles for working police or 
narcotic dogs.• Verify dose and concentration prior to 
administration of opioids therapeutically.
• None routinely expected.
• Possibility for secondary complications in 
rare cases with severe clinical signs.
Prognosis is dose dependent, though generally 
good if clinical signs are controlled.
Potential for co ­ingestion of other medica­
tions/drugs (illicit or prescription).
Neonatal patients may have an increased risk 
of CNS signs due to incomplete blood–brain 
barrier formation.
None
Potential for exposure to fetus, embryos, and 
nursing young.
SYNONYMS
• Codeine—schoolboy, T ­3.
• Desomorphine—krokodil.
• Fentanyl—cash, China white, tango, TNT.
• Heroin—brown sugar, H, hell dust, junk, 
smack, [black] tar.
• Morphine—M, Miss Emma, dreamer.
• ANS = autonomic nervous system.
• GC/MS = gas chromatography–mass 
• LC/MS ­MS = liquid chromatography 
tandem mass spectrometry.
Bischoff K. Toxicity of drugs of abuse. In: 
Veterinary Toxicology: Basic and Clinical 
Principles, 3rd ed. Hopkinsville, KY: 
Elsevier, 2018, pp. 385–408.
ME, Talcott PA, eds., Small Animal 
Toxicology, 3rd ed. Philadelphia, PA: W.B. 
Saunders, 2012, pp. 309–335.
Consulting Editor  Lynn R. Hovda(continued)  Opiates/Opioids Toxicosis

998  Blackwell’s Five-Minute Veterinary Consult  
OOptic Neuritis and Papilledema
  BASICS
• Optic neuritis—inflammation of one or 
both optic nerves, resulting in reduction of 
visual function.
• Papilledema is edema of the optic nerve 
head that does not obviously affect the 
function of the optic nerve.
• Optic neuritis may be a primary disease or 
secondary to CNS disease because the optic 
nerve communicates with the subarachnoid 
space.
• Papilledema occurs when intracranial 
pressure (ICP) is elevated.
• Papilledema may occur separately from 
optic neuritis.
• Optic neuritis may also feature 
papilledema.
• Nervous.
GENETICS
No genetic basis.
Occasional cause of blindness in dogs; rare in 
cats.
N/A
Species
None
Middle-aged.
None
SIGNS
• Optic neuritis—acute blindness, may 
report other neurologic abnormalities such as 
ataxia, seizures, or behavior changes.
• Papilledema—no clinically detectable visual 
abnormalities but may report other neuro-
logic abnormalities attributable to increased 
ICP .
• Optic neuritis—may be unilateral or 
bilateral; absent menace response, absent 
dazzle, mydriatic and nonresponsive pupil; 
may have anisocoria if unilaterally affected. 
Usually, the anterior segment appears normal, 
but hyperemia, congestion, and hemorrhages 
of the optic nerve head are seen. The retina 
surrounding the optic nerve may be detached; 
chorioretinitis can occur concurrently.• Papilledema—usually bilateral, menace 
response is present, dazzle is present, normal 
pupillary light reflexes. The anterior segment 
appears normal, but there is swelling and 
elevation of optic nerve head with loss of the 
physiologic cup in the center of the optic 
nerve head. The retina usually appears 
normal.
CAUSES
Optic Neuritis
• Idiopathic (dogs).
• Systemic mycoses.
• Canine distemper (dogs).
• Feline infectious peritonitis (FIP) (cats).
• Neoplasia—primary or metastatic.
• Neosporum caninum .
• Granulomatous meningoencephalomyelitis.
• Orbital cellulitis.
• Hepatozoonosis.
• Toxicity—lead.
• Tick-borne encephalitis virus.
Papilledema
• CNS neoplasia (primary or metastatic).
• Distemper (dogs).
• FIP (cats).
• Granulomatous mengingoencephalitis.
• T rauma.
None
  DIAGNOSIS
• Papilledema is differentiated from optic 
neuritis by the presence of normal pupillary 
light reflexes and no obvious visual deficits.
• Cortical blindness—normal pupillary light 
reflex; normal fundus examination; possibly 
other neurologic deficits; normal electro  - 
retinogram.
syndrome (SARDS, dogs)—normal to absent 
pupillary light reflex; normal fundus (early in 
course); flat electroretinogram.
Specific viral, protozoal, or fungal serologic 
tests as indicated.
IMAGING
Neuroimaging—MRI and/or CT may 
demonstrate intracranial disease.
• CSF analysis.• Electroretinogram—investigate retinal 
function; normal in patients with optic 
neuritis and papilledema, flat in those with 
SARDS.
• Measure ICP .
  TREATMENT
Inpatient—most cases will need to be 
hospitalized for workup and medical therapy 
depending on the primary disease process.
Depending on degree of neurologic impair-
ment, special attention to patient cleanliness.
ACTIVITY
Activity may need to be restricted if visual 
deficits are present and depending on degree 
of neurologic impairment.
DIET
May need to be altered depending on degree 
Optic neuritis—important to emphasize that 
vision may not return, particularly in 
idiopathic cases, and treatment may be 
life-long (immunosuppressive therapy).
Surgery infrequently indicated.
• Depends on primary disease process when 
identifiable, treat any infectious process 
• Idiopathic—prednisone 2 mg/kg PO q12h 
for 14 days; then 1 mg/kg PO q12h for 14 
days; then gradual reduction to maintenance 
dosage.
• Mannitol 1 g/kg IV over 20 minutes; 
repeated as necessary to treat elevated ICP .
• Hypertonic saline 3 mL/kg IV over 10 
minutes as alternative therapy for elevated 
ICP .
• Corticosteroids—prednisone 0.5 mg/kg PO 
q12h or dexamethasone SP 0.025 mg/kg IV 
q12h; not indicated for head trauma.
Immunosuppressive drugs may be contraindi-
cated in patients where etiology is unknown.
Ensure patients receiving mannitol can urinate; 
immunosuppressive agents should be used 
cautiously in patients with infectious disease.

Canine and Feline, Seventh Edition  999
O
None
  FOLLOW-UP
Serial ophthalmic examinations should be 
performed, including fundic exam. Careful 
attention should be paid to visual deficits; 
resolution of deficits indicates improvement 
in disease, but may also reflect the patient’s 
adaptation to vision loss, making client’s 
reports of vision unreliable.
None
• Optic neuritis—vision loss may be 
• Papilledema—increased ICP may result in 
brain herniation if not treated emergently.EXPECTED COURSE AND PROGNOSIS
• Optic neuritis—guarded to poor prognosis 
for return of vision, but idiopathic cases have 
good prognosis for life.
• Papilledema—guarded to poor prognosis 
for life.
• Optic neuritis—chorioretinitis, CNS 
disease.
• Papilledema—CNS disease.
None
Zoonotic infectious CNS disease is rare.
Infectious diseases such as canine distemper 
may be associated with fetal disease and 
congenital abnormalities.ABBREVIATIONS
• ICP = intracranial pressure.
• SARDS = sudden acquired retinal 
degeneration syndrome.
Montgomery KW, van der Woerdt A, Cottrill 
NB. Acute blindness in dogs: sudden 
acquired retinal degeneration syndrome 
versus neurological disease (140 cases, 
2000–2006). Vet Ophthalmol 2008, 
11:314–320.
Nell, B. Optic neuritis in dogs and cats. Vet 
Clin North Am Small Anim Pract 2008, 
38:403–415.
Acknowledgement  The author/editor 
Amber L. Labelle.(continued)  Optic Neuritis and Papilledema

1000  Blackwell’s Five-Minute Veterinary Consult  
OOral Cavity Tumors, Undifferentiated Malignant Tumors
  BASICS
OVERVIEW
• Uncommon, highly aggressive, rapidly 
growing tumor typically affecting the caudal 
maxilla and orbit of young dogs.
• Most are highly bone-invasive and are 
non-encapsulated with a smooth to slightly 
nodular surface (mistaken as benign); may 
become ulcerated.
• Biopsy—reveals undifferentiated 
malignancy of undetermined histogenesis.
• Highly metastatic—regional lymphatic 
spread and distant sites.
• Local disease often represents life-limiting 
issue despite the high metastatic propensity.
• Dog.
• Primarily a disease of large breeds.
• All dogs <2 years old; range 6–22 months.
• No sex predilection reported.
SIGNS
• Excessive salivation.
• Hyporexia.
• Bloody oral discharge.
• Oral mass.
• Loose teeth.
• Facial deformity, exophthalmia.
• Regional lymphadenopathy.
• Pain upon palpating or opening the mouth.
  DIAGNOSIS
• Other aggressive oral malignancy such as 
oral melanoma, squamous cell carcinoma, or 
• Acanthomatous ameloblastoma/peripheral 
odontogenic fibroma.
• Tooth root abscess.
Often normal.
N/A
IMAGING
• High detail skull/dental radiography—
evaluate for osteolytic changes.
• 3-view thoracic radiography—detect lung 
metastasis.• Advanced sectional imaging (CT or 
MRI)—define local and regional/distant 
extent of disease, and facilitate therapeutic 
planning.
• Carefully palpate regional lymph nodes 
(mandibular, retropharyngeal, superficial 
cervical).
• Cytologic evaluation of primary tumor and 
regional lymph nodes may provide tentative 
diagnosis of malignancy.
• Large, deep-tissue biopsy required to 
differentiate from other oral malignancies.
• Fine-needle aspiration or biopsies of 
inside the mouth, not through the overlying 
skin (could compromise local control with 
surgery).
• Histopathology consistent with an 
undifferentiated tumor without characteristic 
morphologic features of mesenchymal or 
epithelial origin.
• Immunocytochemistry (various markers) 
required to rule out other tumors, including 
rhabdomyosarcoma (aggressive tumor also 
seen in young dogs).
  TREATMENT
Diet
Soft food recommended to prevent tumor 
ulceration or following radical oral excision.
• Radical surgical excision—often ineffective 
because of extensive local disease or regional 
metastasis at diagnosis.
• If attempted, must have margins of at 
least 2 cm into normal bone and soft tissues 
and ideally be planned with the help of 
contrast-enhanced advanced sectional 
imaging.
• Efficacy unreported.
• Undifferentiated tumors often poorly 
responsive to megavoltage radiation therapy.
• Considered for palliation (hypofractionated 
protocol).
• Chemotherapy—efficacy unreported; 
undifferentiated tumors often poorly 
responsive to systemic chemotherapy.
• Pain management with multimodal 
analgesic therapy is mandatory (nonsteroidal 
anti-inflammatory drug, opioid, adjuvant 
analgesic medications, aminobisphosphonate 
if osteolysis is present).CONTRAINDICATIONS/POSSIBLE 
Chemotherapy can be toxic; seek advice of a 
medical oncologist before initiating treatment 
if you are unfamiliar with cytotoxic drugs.
  FOLLOW-UP
• Most dogs have detectable metastatic 
dissemination at diagnosis.
• Patients often euthanized within 30 days of 
diagnosis because tumor growth is progressive 
and uncontrolled, resulting in decreased 
quality of life and condition.
Patnaik AL, Lieberman PH, Erlandson RA, 
et al. A clinicopathologic and ultrastructural 
study of undifferentiated malignant tumors 
of the oral cavity in dogs. Vet Pathol 1986, 
23:170–175.

Canine and Feline, Seventh Edition  1001
O
Orbital Diseases (Exophthalmos, Enophthalmos, Strabismus)
  BASICS
• Abnormal position of the globe.
• Exophthalmos—anterior displacement of 
the globe.
• Enophthalmos—posterior displacement of 
the globe.
• Strabismus—deviation of the globe from 
the correct position of fixation, which the 
patient cannot correct.
• Orbit cannot be examined directly; orbital 
disease manifested by signs that alter the position, 
appearance, or function of the globe and adnexa.
• Malpositioned globe—caused by changes in 
volume (loss or gain) of the orbital contents 
or abnormal extraocular muscle function.
• Exophthalmos—caused by space-occupying 
lesions posterior to the equator of the globe.
• Enophthalmos—caused by loss of orbital 
volume, Horner’s syndrome, or space-occupying 
lesions anterior to the equator of the globe.
• Strabismus—usually caused by an imbalance 
of extraocular muscle tone or lesions that 
restrict extraocular muscle mobility.
• Respiratory—because of proximity, the 
nasal cavity and frontal and maxillary sinuses 
may be involved.
• Orbital abscess or cellulitis and myositis—
more common in young adult dogs.
• Myositis—predisposed breeds: German 
shepherd dog, golden retriever, Weimaraner.
• Orbital neoplasia—more common in 
middle-aged to old dogs.
SIGNS
Exophthalmos
• Secondary signs of space-occupying orbital 
disease.
• Difficulty in retropulsing the globe.
• Serous to mucopurulent ocular discharge.
• Chemosis.
• Eyelid swelling.
• Lagophthalmos—inability to close the 
eyelids over the cornea during blinking.
• Exposure keratitis—with or without ulceration.
• Pain on opening the mouth.
• Third eyelid protrusion due to extraconal 
mass or advanced intraconal mass.
• Visual impairment due to optic neuropathy.
• Fundic abnormalities, including retinal 
detachment, retinal vascular congestion, optic 
disc swelling.
• Focal inward deviation of the posterior globe.
• Neurotropic keratitis after damage to the 
ophthalmic branch of cranial nerve V.• Fever and malaise—with orbital abscess or 
cellulitis.
• Intraocular pressure (IOP)—rarely high.
Enophthalmos
• Ptosis.
• Third eyelid protrusion.
• Extraocular muscle atrophy.
• Entropion—with severe disease.
Strabismus
• Deviation of one or both eyes from the 
normal position.
• May note exophthalmos or enophthalmos.
CAUSES
• Neoplasm—primary or secondary.
• Abscess or cellulitis—bacterial or fungal; fungal 
more likely in cats; look for foreign bodies:
◦ Bacterial infections may be mixed; 
Pasteurella multocida  and Enterobacteriaceae  
common.
• Zygomatic mucocele—not described in cats.
• Myositis—muscles of mastication or 
extraocular muscles (eosinophilic or extra -
ocular polymyositis).
• Orbital hemorrhage secondary to trauma.
• Arteriovenous fistula or varix—rare.
• Ocular pain.
• Microphthalmia.
• Phthisis bulbi.
• Collapsed globe.
• Loss of orbital fat or muscle.
• Conformational enophthalmos in 
dolichocephalic breeds.
• Neoplasia—especially if originating from 
rostral orbit.
• Abnormal innervation of extraocular muscle.
• Restriction of extraocular muscle mobility 
by scar tissue from previous trauma or 
• Destruction of extraocular muscle 
attachments after proptosis.
• Convergent strabismus—congenital; results 
from abnormal crossing of visual fibers in the 
CNS (Siamese cats).
• Shar-pei strabismus.
Proptosis—more common in brachycephalic 
dogs with shallow orbits.
  DIAGNOSIS
• Buphthalmic globe—may simulate a 
space-occupying mass causing anterior displacement of the eye owing to its size in 
relationship to the orbital volume; IOP 
usually high; corneal diameter greater than 
normal, corneal edema, mydriatic pupil, optic 
nerve cupping (i.e., signs of glaucoma), 
blindness.
• Episcleritis—may cause severe diffuse or 
focal thickening of the fibrous tunic, 
imitating a buphthalmic globe; corneal 
edema; normal or low IOP; aqueous flare.
Causes
• Acute onset of exophthalmos—often with 
inflammatory orbital disease. Pain, especially 
on opening the mouth, is more likely 
inflammatory orbital disease than orbital 
• Salivary mucoceles—more variable in 
speed of onset and degree of patient 
• Extraocular or eosinophilic myositis—
bilateral diseases; Neospora caninum  caused 
extraocular polymyositis in a litter of dogs.
• Neoplasia—usually slowly progressive, 
nonpainful, unilateral exophthalmos.
• Leukogram—may show inflammation 
(abscess, cellulitis, or myositis).
• Peripheral eosinophilia—occasionally seen 
in dogs with eosinophilic (masticatory 
muscle) myositis.
IMAGING
• Orbital ultrasonography, CT and MRI—
define the extent of the lesion(s) and 
distinguish between types of myositis.
• Skull radiographs (especially of the frontal 
sinuses and nasal cavity).
• Thoracic radiographs—to identify 
• Lack of globe retropulsion—confirms 
space-occupying mass.
• Oral examination, ocular ultrasound, and 
fine-needle aspiration (FNA) of the orbit—
may require anesthesia.
• FNA (18- to 20-gauge)—submit samples 
for aerobic and anaerobic bacterial cultures, 
Gram staining, and cytologic examination.
• Cytology—often diagnostic for abscess or 
cellulitis, zygomatic salivary gland mucocele, 
and neoplasia.
• Biopsy—indicated if FNA is nondiagnostic. 
Biopsy of masseter, temporal, or extraocular 
muscle if myositis suspected; assays for type 
2M fibers may be helpful.
• Forced duction of the globe (strabismus)—
grasp the conjunctiva with a fine pair of 
forceps following topical anesthesia; 
differentiates neurologic disease (globe moves 
freely) from restrictive condition (globe 
cannot be moved manually).

1002  Blackwell’s Five-Minute Veterinary Consult  
O  TREATMENT
Proptosis
See Proptosis.
Orbital Abscess or Cellulitis
• Drainage is seen in less than half of patients, 
usually because the lesion is just cellulitis and 
a true abscess has not yet formed.
• If an obvious swelling of the oral mucosa 
behind the last molar is not present and 
ultrasound does not show an abscess, it is best 
to avoid incising the oral mucosa and treat with 
systemic antibiotics and anti-inflammatory 
medications; the affected globe should also be 
kept moist with topical lubricants q6h.
• Severe cases may require IV fluids to restore 
and maintain hydration until patient is able 
to eat.
• If a swelling of the oral mucosa behind the 
last molar is evident, establish ventral orbital 
drainage:
◦ Incise the surgically prepared mucosa 
approximately 1 cm behind the last molar.
◦ Push blunt-tipped forceps (e.g., Kelly or 
Carmalt) into the orbital space and open; in 
general, advance the forceps until the 
abscess drains, to the level of the box lock, 
or until movement of the eye occurs with 
forceps opening.
◦ Minimize retrobulbar trauma and optic 
nerve damage; use only blunt dissection; 
never cut or crush tissue.
◦ Complications from aggressive dissection 
include damage to the optic and ciliary nerves.
◦ Collect samples for bacterial culture and 
cytologic examination through this port.
• Feed soft food until globe is back in normal 
position and pain resolved.
• Hot packing—q6h; helps decrease swelling 
and cleans discharge.
Orbital Neoplasms
• Usually primary and malignant.
• Early exenteration or orbital exploratory 
surgery and mass debulking via a lateral 
approach to the orbit to save the globe are 
rational therapeutic choices.
• Adjunctive chemotherapy or radiotherapy—  
depending on neoplasm and extent of the 
lesion.
• Without adjunct therapy—survival is weeks 
to months if malignant (patients are usually 
presented late in the course of disease).• Consultation with an oncologist is 
recommended once the diagnosis is made.
Zygomatic Mucocele
May resolve with antibiotic and corticosteroid 
administration; if not, surgical excision of the 
cyst and associated salivary gland is usually 
curative.
• Neurologic—Identify and treat the 
underlying cause, if possible.
• Restrictive or post-traumatic—may be 
treated surgically by repositioning or excising 
the attachments of extraocular muscles to 
relieve excessive tension on those muscles; 
usually a very difficult procedure.
• Exophthalmos (all patients)—lubricate 
cornea with artificial tear ointment or gel, 
q6h, to prevent desiccation and ulceration.
• Corneal ulceration—topical antibiotic (e.g., 
bacitracin, neomycin, polymyxin, q8h) and 
cycloplegic (e.g., 1% atropine, q12–24h), to 
prevent infection and reduce ciliary spasm, 
• Oral or IV antibiotics—ampicillin 20 mg/
kg q8h ×2–3 weeks or drugs with an 
anaerobic spectrum (amoxicillin with 
clavulanic acid or clindamycin) should be 
considered while awaiting results of bacterial 
culture and cytologic examination, or if client 
declines diagnostic testing.
• Fluconazole 2.5 mg/kg PO q12h or 5 mg/
kg PO q24h or posaconazole 5 mg/kg PO 
q12h for orbital aspergillosis.
• Prednisone 1 mg/kg SC, IM q24h, once, to 
minimize optic neuritis and reduce orbital 
swelling and globe exposure (severe cases).
• Nonsteroidal anti-inflammatory drugs can 
be used in place of prednisone and 
administered for a longer period.
Acute Myositis
• Difficult prehension—systemic 
corticosteroids (prednisone 2 mg/kg SC, IM), 
then oral (prednisone 2 mg/kg q24h) for 4–6 
weeks until swelling subsides; then taper.
• Azathioprine 1–2 mg/kg PO q24h for 3–7 
days then q48h and taper, with or without corticosteroids. May be used chronically to 
manage recurrent disease.
• Systemic corticosteroids—extreme caution 
with deep fungal orbital disease.
• Azathioprine—may be hepatotoxic and 
cause myelosuppression. Follow CBC and 
liver enzyme activities every 1–2 weeks for 8 
weeks, then periodically.
  FOLLOW-UP
• Inflammatory orbital disease—examine at 
least weekly until clinical signs abate.
• Advise client to watch for recurrence of 
signs, especially if an orbital foreign body 
likely.
• T reat fungal infections for 60 days after 
signs resolve.
• Loss of the eye.
• Permanent malposition of the globe.
• Death.
Give a course of antibiotic therapy first prior 
to attempting ventral orbital drainage.
Avoid systemic corticosteroids, antifungals, 
and azathioprine in pregnant animals.
SEE ALSO
• Red Eye.
• FNA = fine-needle aspiration.
Miller PE. Orbit. In: Maggs DJ, Miller PE, 
Ofri R, eds., Slatter’s Fundamentals of 
Veterinary Ophthalmology, 5th ed. St. 
Louis, MO: Elsevier, 2013, pp. 352–373.
Consulting Editor  Kathern E. MyrnaOrbital Diseases (Exophthalmos, Enophthalmos, Strabismus)  (continued)

Canine and Feline, Seventh Edition  1003
O
Organophosphorus and Carbamate Toxicosis
  BASICS
• Results from exposure to organophosphorus 
compounds or carbamates.
• Calls to the American Society for the 
Animal Poison Control Center (APCC) 
regarding exposure to organophosphorus 
compounds continue to decrease. In 2017, 
organophosphate and carbamate exposures 
represented only 2.2% of insecticide-related 
exposure calls..
• The decrease is likely related to EPA 
cancellations of various registrations and 
approval of new, less hazardous compounds 
and delivery formulations. Canceled 
products, however, often remain in homes 
and businesses for years. In 2017 the most 
commonly reported exposures from most to 
least were to products containing propoxur, 
acephate, carbaryl, and tetrachlorvinphos.
• Animal products—organophosphate: 
chlorpyrifos, coumaphos, cythioate, 
diazinon, famphur, fenthion, phosmet, and 
tetrachlorvinphos; carbamate: carbaryl and 
propoxur. (Many animal products containing 
phosmet, tetrachlorvinphos, carbaryl, 
chlorpyrifos, diazinon [all] have been 
discontinued.)
• Agricultural, lawn, and garden products—
organophosphate: acephate, chlorpyrifos, 
diazinon, disulfoton, fonofos, malathion, 
parathion, terbufos, and others; carbamate: 
carbofuran and methomyl. (Same comment 
as above for environmental products.)
• Cause nervous system effects by inhibiting 
cholinesterase, which includes acetylcholinesterase, 
pseudocholinesterase, other esterases.
• Acetylcholinesterase—normally hydrolyzes 
the neurotransmitter acetylcholine in nervous 
tissue, red blood cells, and muscle, resulting 
in termination of nervous transmission.
• Pseudocholinesterase—found in plasma, 
liver, pancreas, nervous tissue; mainly in cats.
• Cholinesterase inhibition—allows 
acetylcholine accumulation at the postsynaptic 
receptor; causes stimulation of effector organs; 
spontaneous reactivation after organophos -
phorus compound binding is very slow and 
once aging occurs is virtually nonexistent; 
reversible after carbamate binding.
Nervous—results from overriding stimulation 
of parasympathetic pathways; may also result 
from sympathetic stimulation; acetylcholine 
stimulates nicotinic receptors of the somatic 
nervous system (skeletal muscle), parasym -
pathetic preganglionic nicotinic and 
postganglionic muscarinic receptors (cardiac 
muscle, pupil, blood vessels, smooth muscles in lung and gastrointestinal tract, exocrine 
glands), and sympathetic preganglionic 
nicotinic receptors (adrenal and indirectly 
cardiac muscle, pupil, blood vessels, smooth 
muscles in lung and gastrointestinal tract, 
exocrine glands).
GENETICS
• Animals with inherently low cholinesterase 
activity—more susceptible to cholinesterase 
• Cholinesterase activity—more easily 
inhibited in cats than in dogs.
Uncommon in small animals.
Historically more common in areas of high 
flea prevalence and intense agricultural 
activity.
Species
• Cats most susceptible.
Lean dogs (e.g., sight hounds and racing 
breeds) and lean longhaired cats—more 
susceptible to cholinesterase inhibition 
because of lack of fat; many organopho -
sphorus compounds and metabolites are 
stored in fat and slowly released into 
Young animals—more likely intoxicated due 
to lower detoxification capability.
Intact males more susceptible to some 
organophosphates.
SIGNS
• Parasympathetic stimulation—usually 
predominates.
• Sympathetic stimulation—may result in 
lack of specific expected signs; may note signs 
opposite from expected.
• Medical history—often discloses heavy or 
repeated applications of flea and tick 
insecticides; evidence of exposure to an 
agricultural or home and garden product.
• Carbamate insecticides (methomyl and 
carbofuran)—may cause rapid onset of 
seizures, respiratory failure, and death; treat 
aggressively without delay.
• Organophosphate insecticides (cats, 
especially chlorpyrifos)—chronic anorexia, 
muscle weakness and twitching, with or 
without episodes of acute toxicosis; may last 
days to weeks.
• Vomiting.• Diarrhea.
• Miosis.
• Bradycardia.
• Ataxia.
• Muscle tremors.
• Dyspnea.
• Respiratory failure.
• Death.
• Patient may not exhibit all signs.
• Sympathetic stimulation—signs reversed.
CAUSES
• Overuse, misuse, or use of multiple 
cholinesterase-inhibiting insecticides.
• Misuse of organophosphate insecticides in 
cats (e.g., organophosphate-containing dips 
labeled for dogs only, inappropriately applied 
to cats).
• Intentional dermal application of house or 
yard insecticides.
• Concurrent exposure to multiple products 
containing organophosphate and/or carbamate.
• Exposure to floors that are damp with 
organophosphorus premise products.
• Incorrect dilution of insecticides.
  DIAGNOSIS
• Exposure to other insecticidal products—
pyrethrin/pyrethroids (flea and tick); 
d-limonene (citrus flea and tick); fipronil (flea 
and tick); imidacloprid (flea).
• Other pesticides—strychnine; fluoroacetate 
(1080); 4-aminopyridine (avicide); metaldehyde 
(snail bait); zinc/aluminum phosphide 
(rodenticide); bromethalin (rodenticide).
• Other toxicants—chocolate; caffeine; 
cocaine; amphetamine; tremorgenic 
mycotoxins.
N/A
Cholinesterase Activity
• Reduced to <25% of normal in whole 
blood, retina, or brain—suggests exposure to 
a cholinesterase-inhibiting compound; must 
compare to normal reference values in that 
species generated by the same laboratory.
• Test results—must be interpreted in context 
of the amount of exposure and the clinical 
signs and the time of their onset.
• Use laboratories experienced in handling 
animal samples.
• Chlorpyrifos—experimentally exposed 
animals may remain clinically normal with no 
detectable cholinesterase activity.

1004  Blackwell’s Five-Minute Veterinary Consult  
O• Carbamate inhibition—reactivation can 
occur during sample transport, storage, and 
testing, giving false-negative results.
• Atropine response test—administer atropine at 
pre-anesthetic dose (0.02 mg/kg IV). 
Antimuscarinic response (tachycardia, mydriasis) 
suggests lack of anticholinesterase exposure.
• Detection of insecticides—tissue (e.g., 
brain, liver, kidney, and fat); stomach 
contents; gastrointestinal tract; fur or hair; 
negative results do not rule out toxicosis.
• May find pieces of chewed containers in the 
• Histopathologic lesions—rare, no 
characteristic lesions likely in acute toxicosis.
• Delayed neuropathy—not usually 
associated with commercially available 
organophosphorus compounds.
  TREATMENT
• Outpatient—mild signs from exposure to 
flea and tick collars and powders; treat by 
removing the collar or brushing excess 
powder from the coat.
• Inpatient—continued salivation, tremors, 
or dyspnea.
• Basics—stabilization; decontamination; 
antidotal treatment with atropine (and 
pralidoxime chloride for organophosphate 
toxicosis); supportive care.
• Control seizure activity, tremors.
• Oxygen—if necessary, until respiration 
returns to normal.
• Fluid therapy—may be needed in anorexic 
cats and dehydrated animals.
• Bathing (dermal exposure)—use hand 
dish-washing detergent; rinse with copious 
amounts of water.
DIET
Chronically anorexic cats—maintain 
nutritional and fluid requirements.
• Stress the importance of following 
insecticide label directions.
• Caution client that cats with chronic 
anorexia and weakness may need days to 
weeks of supportive care for full recovery.
• Emesis:
◦ Ingestion of liquid insecticidal solution—
avoid inducing emesis; risk of aspiration because many solutions contain hydro -
carbon solvents.
◦ Liquid solvent not ingested, no clinical 
signs, and very recent ingestion—induce 
emesis with 3% hydrogen peroxide 
(2.2 mL/kg PO to a maximum of 45 mL) 
after feeding a moist meal.
• Activated charcoal:
◦ Evacuation of the stomach for patient 
with clinical signs—gastric lavage with the 
patient intubated, under anesthesia, with a 
large-bore stomach tube; then administration 
of activated charcoal (2 g/kg PO) containing 
sorbitol as a cathartic in a water slurry.
◦ Diarrhea—do not administer sorbitol-
containing products.
• Diazepam (0.5–1 mg/kg IV to effect) used 
initially for seizures. Pentobarbital (5–15 mg/
kg IV to effect) added for persistent seizure 
activity. Phenobarbital (3–30 mg/kg IV to 
effect, low dosage in cats), propofol (3–6 mg/
kg IV or 0.1 mg/kg/min CRI) or levetiracetam 
(30–60 mg/kg slow IV bolus in dogs; 20 mg/
kg IV in cats) can be used for refractory 
seizures.
• Atropine sulfate—0.2 mg/kg one-quarter 
IV, remaining SC, as needed; administered 
immediately; repeated only as needed to 
control life-threatening clinical signs from 
muscarinic stimulation.
• Pralidoxime chloride (Protopam) 
10–15 mg/kg IM, SC q8–12h until 
recovery; discontinue after 3 doses if no 
response; reduces muscle fasciculations; 
most beneficial against organophosphorus 
insecticides when started within 24 hours of 
exposure; even several days after dermal 
exposure may stimulate anorexic cats (with 
or without tremors) to resume eating; if 
refrigerated and wrapped in foil, 
reconstituted bottles may be successfully 
used for up to 2 weeks.
Phenothiazine tranquilizers may potentiate 
organophosphate toxicosis.
Atropine—avoid overuse; may cause 
tachycardia, CNS stimulation, seizures, 
disorientation, drowsiness, and respiratory 
N/A
N/A
  FOLLOW-UP
Monitor heart rate, respiration, and fluid and 
caloric intake.PREVENTION/AVOIDANCE
• Follow directions on insecticide labels 
closely.
• Avoid use on sick or debilitated animals.
• Avoid simultaneous use of organophosphate 
and carbamate products.
N/A
EXPECTED CIOURSE 
• Chronic organophosphate insecticide-
induced weakness and anorexia (cats, 
chlorpyrifos exposure)—may last 2–4 weeks; 
most patients fully recover with aggressive 
nursing care.
• Acute toxicosis treated promptly—good 
N/A
Young animals have lower detoxification 
ability.
None
N/A
SEE ALSO
• APCC = Animal Poison Control Center.
• ASPCA = American Society for the 
Fikes JD. Organophosphate and carbamate 
insecticides. Vet Clin North Am Small 
Anim Pract 1990, 20:353–367.
Means C. Organophosphate and carbamate 
insecticides. In: Peterson ME, Talcott PA, 
eds., Small Animal Toxicology, 3rd ed. St. 
Louis, MO: Elsevier, 2013, pp. 715–723.
Authors  Steven R. Hansen and Elizabeth A. 
Curry-Galvin
available onlineOrganophosphorus and Carbamate Toxicosis  (continued)

Canine and Feline, Seventh Edition  1005
O
Oronasal Fistula
  BASICS
OVERVIEW
• An oronasal fistula is an abnormal 
connection between the oral and nasal 
cavities.
• which can occur from pathology of any of 
the tissues surrounding the maxillary teeth or 
• The maxillary canines are most commonly 
involved.
• The palatal root of the maxillary fourth 
premolar is the next most common area 
involved.
• Dogs—dolichocephalic head types are 
affected most often, especially dachshunds.
• Cats—rare
SIGNS
• Chronic rhinitis—with or without blood.
• Sneezing—common, especially when the 
maxillary canines are digitally palpated.
• Usually associated with advanced-
periodontitis (PD4) of the maxillary canine 
tooth, leading to destruction of the bone 
separating the nasal and oral cavities.
• Other causes include trauma, penetration of 
a foreign body, bite wounds, traumatic tooth 
extraction, electrical shock, or oral cancer.
• Fistula width can be related to the size of 
the tooth affected; fistula depth to the 
chronicity of the periodontal infection.
• Dogs with lingually displaced (mesioverted) 
mandibular canines, mandibular distoclusion 
(overbite) resulting in penetration of the hard 
palate are predisposed to oronasal fistulas.
• Dachshunds predisposed.
  DIAGNOSIS
• Oral neoplasia.
• T rauma.
• Foreign body penetration.
N/A
N/A
IMAGING
• Skull radiographs rarely helpful in 
diagnosing oronasal fistula because the lesions 
are generally isolated to the palatal surface.
• Intraoral radiographs are highly 
recommended to evaluate the periodontal 
status of the patient’s teeth.• Radiographs may show foreign body 
entrapment or lysis consistent with neoplasia.
Periodontal probing-—results in direct 
extension into the nasal cavity or epistaxis in 
cases of oronasal fistula. Periodontal probing 
will also identify areas where significant 
palatal defects are present which can be 
treated to help prevent the occurrence of 
oronasal fistulas.
  TREATMENT
• Extract the tooth and close the defect; after 
extraction, the goal of surgical closure is to 
place an epithelial layer in both the oral and 
nasal cavities.
• Full-thickness flap—after tooth extraction, 
a mucoperiosteal pedicle flap may be elevated 
from the dorsal aspect of the fistula, released, 
advanced to cover the defect, and sutured in 
place; a successful full-thickness flap requires 
at least 2 mm attached gingiva above the 
defect, with sutures at the edge of the defect 
(not over the void), without tension on the 
suture line.
• Double reposition flap—used for large 
fistulas or repair failures where no attached 
gingiva remains or where periosteal tissue 
cannot be included; after extraction, the first 
flap is harvested from the hard palate and 
inverted so that the oral epithelium is toward 
the nasal passage; the second flap is muco -
buccal and harvested from the alveolar 
mucosa and underside of the lip rostral to the 
fistula; it is sutured over the first flap and 
donor site.
• Guided tissue regeneration of the maxillary 
canine—may be used for repair of a deep 
palatal pocket if not yet fistulated; a palatal 
flap is elevated to approach the infrabony 
defect; soft tissue and calculus are removed 
from the defect with a curette.
• In deep, infrabony pockets before 
fistulation, bone grafts such as PerioGlas, 
Consil, synthetic and natural hydroxyapatite, 
autogenous and heterologous bone, polylactic 
acid, and Osteoallograft (freeze-dried canine 
cadaver bone) have been used to exclude 
regrowth of gingival connective tissue and 
epithelium, promoting regeneration of bone 
and periodontal ligament. Implant materials 
should not be used if an oronasal fistula is 
present.
• Ear cartilage has been used as a membrane 
to cover the defect before closure.
• Oroantral fistulas located in the central 
portion of the hard palate may be surgically 
repaired with a transposition flap of the hard 
palate mucoperiosteum from tissue adjacent 
to the defect.  MEDICATIONS
N/A
N/A
  FOLLOW-UP
Normal postoperative monitoring.
Even with adequate tissue, excellent release of 
tension on the flap, and good technique, a 
persistent opening may occur due to constant 
tension on the site during each breath. With 
inadequate tissue or technique, the prognosis 
decreases, and additional surgeries with 
advanced flaps may be required.
Bellows JE, Small Animal Dental Equipment 
and Techniques 2nd ed, Ames, IA: Wiley 
Lorrain RP , Legendre LF . Oronasal fistula 
repair using auricular cartilage. J Vet Dent 
2012, 29(3):172–175.

1006  Blackwell’s Five-Minute Veterinary Consult  
OOsteochondrodysplasia
  BASICS
OVERVIEW
• A developmental abnormality of cartilage 
and bone; encompasses many disorders 
involving bone growth. • Results from 
abnormal endochondral ossification. 
• Skeletal defects—usually involve the 
appendicular skeleton; specifically the 
metaphyseal growth plates. 
• Achondroplasia—failure of cartilage growth; 
characterized by a proportionate short-limbed 
dysplasia; evident soon after birth. 
• Hypochondrodysplasia—less severe form 
of achondrodysplasia. • Characteristic 
breeds—result of selection of certain desirable 
traits. • Affects musculoskeletal and possibly 
ophthalmic systems.
• Achondroplastic breeds—bulldog; Boston 
terrier; pug; Pekingese; Japanese spaniel; shih tzu. 
• Hypochondroplastic breeds—dachshund; 
basset hound; beagle; Welsh corgi; Dandie 
Dinmont terrier; Scottish terrier; Skye terrier. 
• Reported nonselected chondrodysplastic 
abnormalities—Alaskan Malamute; Samoyed; 
Labrador retriever; English pointer; Norwegian 
elkhound; Great Pyrenees; cocker spaniel; Scottish 
terrier; Scottish deerhound; beagle; miniature 
poodle; French bulldog; Scottish fold cat. 
• Oculoskeletal dysplasia—diagnosed in 
Labrador retriever and Samoyed.
SIGNS
Phenotypically normal at birth, retardation of 
growth recognized in first few months of life.
• Usually affects the appendicular skeleton; 
may affect axial skeleton. • Long bones—
appear shorter than normal; often bowed. 
• Major joints (elbow, stifle, carpus, tarsus)—
appear enlarged. • Radius and ulna—often 
severely affected owing to asynchronous 
growth. • Lateral bowing of the forelimbs. 
• Enlarged carpal joints. • Valgus deformity 
of the paws. • Shortened maxilla—relative 
mandibular prognathism. • Spinal devia-
tions—due to vertebral abnormalities (hemi, 
wedge, block, transitional, etc.). • Retina—
dysplasia; partial to complete detachment.
• Achondrodysplastic and hypochondrodys-
plastic breeds—autosomal dominant trait. 
• Nonselected chondrodysplastic breeds—
autosomal recessive or polygenic trait. 
• Littermates often affected. • Congenital 
hypothyroidism. • Autosomal incomplete 
dominant trait in Scottish folds.  DIAGNOSIS
• Premature closure of the ulnar or radial 
physes—history of trauma; no other bones 
affected; unilateral or bilateral abnormalities. 
• Pituitary dwarfism.
IMAGING
• Radiography of affected limbs—irregular 
flattening of the metaphysis; stippled 
appearance of epiphyses; widening of the 
physeal line; retained endochondral cores; 
irregularities in ossification of the affected 
long bone; degenerative joint disease and 
joint laxity owing to abnormal stress and 
weightbearing on the limbs. • Radiography of 
the spine—hemivertebrae; wedge-shaped 
vertebrae. Tail/caudal vertebrae—bony 
proliferation, shortened and malformed, 
reduced intervertebral spaces.
Bone biopsy of growth plate—definitive diagnosis.
Histologic findings—disorganization of the 
proliferative zone, abnormalities within the 
hypertrophic zone, abnormal formation of 
the primary and secondary spongiosa.
  TREATMENT
• Achondrodysplasia—considered a normal 
abnormality in some (chondrodystrophic) breeds. 
• Surgery—usually of little benefit for 
nonselected chondrodysplasia. • Corrective 
osteotomy to realign limb(s) or joint(s)—may 
have limited benefit. • Radiation therapy—
pain relief for long periods in Scottish folds.
• Analgesics and anti-inflammatory agents—
palliative use warranted. ◦ Carprofen 2.2 mg/
kg PO q12h or q24h. ◦ Deracoxib 1–2 mg/
kg PO q24h. ◦ Firocoxib 5 mg/kg PO q24h. 
◦ Gabapentin 10–20 mg/kg PO q8h. 
◦ Gapiprant 2 mg/kg/day PO. ◦ Meloxicam 
q24h—liquid). ◦ T ramadol 4–10 mg/kg PO 
q8–12h. • Chondroprotective agents—poly-
sulfated glycosaminoglycans, glucosamine, 
and chondroitin sulfate; may have limited 
benefit in preventing articular cartilage 
changes.  FOLLOW-UP
breeding affected animals.
Intra-articular and periarticular joint structures—
degenerate owing to abnormal conformation of 
the appendicular skeleton; leads to altered 
biomechanics; results in poor quality of life.
SYNONYMS
• Cherubism, • Dwarfism.
drug.
Franch J, Font J, Ramis A, et al. Multiple 
cartilaginous exostosis in a Golden retriever 
cross-bred puppy: clinical, radiographic and 
backscattered scanning microscopy findings. 
Vet Comp Orthop T raumatol 2005, 
18(3):189–193.
Horton WA. The evolving definition of a 
chondrodysplasia. Pediatr Pathol Mol Med 
2003, 22(1):47–52.
Jacobson LS, Kirberger RM. Canine multiple 
cartilaginous exostoses: unusual 
manifestations and a review of the literature. 
J Am Anim Hosp Assoc 1996, 32(1):45–51.
Kyostila K, Lappalainen KS, Lohi H. Canine 
chondrodysplasia caused by a truncating 
mutation in collagen-binding integrin alpha 
subunit 10. PLoS ONE 2013, 8(9):e75621.
Malik R, Allan GS, Howlett CR, et al. 
Osteochondrodysplasia in Scottish Fold 
cats. Aust Vet J 1999, 77(2):85–92.
Martinez S, Fajardo R, Valdes J, et al. 
Histopathologic study of long-bone growth 
plates confirms the basset hound as an 
osteochondrodysplastic breed. Can J Vet 
Res 2007, 71(1):66–69.
Neff MW, Beck JS, Koeman JM, et al. Partial 
deletion of the sulfate transporter SLC13A1  
is associated with an osteochondrodysplasia 
in the miniature poodle breed. PLoS ONE 
2012, 7(12):e51917.
Rorvik AM, Teige J, Ottesen N, Lingass F . 
Clinical, radiographic, and pathologic 
abnormalities in dogs with multiple 
epiphyseal dysplasia: 19 cases (1991–2005). 
J Am Vet Med Assoc 2008, 233:600–606.
Authors  Annika Sundby and Wesley J. Roach

Canine and Feline, Seventh Edition  1007
O
  BASICS
A pathologic process in growing cartilage, 
primarily characterized by a disturbance of 
endochondral ossification that leads to 
excessive retention of cartilage.
• Cells of the immature articular joint 
cartilage and growth plates do not 
differentiate normally.
• For articular cartilage, the process of 
endochondral ossification is retarded, 
presumably due to localized, focal disruption 
of blood supply. If blood supply is 
reestablished, healing occurs. Alternatively, if 
blood supply is not reestablished, cartilage 
remains thick and there is separation between 
the cartilage and subchondral bone. 
Eventually a fissure occurs through the 
articular cartilage that allows communication 
with the joint cavity. The result is creation of 
a cartilage flap that is separated from the 
underlying subchondral bone; this condition 
is known as osteochondritis dissecans (OCD).
• Bilateral disease common.
• Most commonly affected joints—shoulder 
(caudocentral humeral head); elbow (medial 
aspect of the humeral condyle); stifle (femoral 
condyle, lateral more often than medial); 
hock (ridge of the talus, medial more 
common than lateral).
• Other reported locations—femoral head; 
dorsal rim of the acetabulum; glenoid cavity 
(scapula); patella; distal radius; medial 
malleolus; cranial end plate of the sacrum; 
vertebral articular facets; cervical vertebrae.
Immature Joint Cartilage
• Thickened cartilage results in impaired 
metabolism, leading to degeneration and 
necrosis of the poorly supplied cells.
• Fissure within the thickened cartilage—may 
result from mechanical stress; eventually leads 
to the formation of a cartilage flap or OCD; 
may cause lameness.
• Lameness (pain)—usually becomes evident 
once OCD develops; osteochondrosis is often 
Retention of Cartilage in Growth Plates
• Usually does not lead to necrosis, probably 
owing to nutrition provided by vessels within 
the cartilage.
• Failure of endochondral ossification can lead 
to decreased longitudinal bone growth. When 
this is severe and occurs in the distal ulnar 
physis, angular limb deformity may result.
MusculoskeletalGENETICS
• Polygenetic transmission—expression 
determined by an interaction of genetic and 
environmental factors.
• Heritability index—depends on breed; 
0.25–0.45.
Frequent and serious problem in many dog 
breeds.
N/A
Species
Dog
Large and giant breeds—Great Dane, 
Labrador retriever, Newfoundland, Rottweiler, 
Bernese mountain dog, English setter, Old 
English sheepdog.
• Onset of clinical signs—typically 4–8 
months.
• Diagnosis—generally 4–18 months.
• Symptoms of osteoarthritis—any age.
• Shoulder—males (2:1).
• Elbow, stifle, and hock—none.
SIGNS
Depend on the affected joint(s) and 
concurrent osteoarthritis.
Lameness—most common; sudden or 
insidious in onset; one or more limbs; 
becomes worse after exercise; duration of 
several weeks to months; slight, moderate, or 
severe.
• Pain—usually elicited on palpation by 
flexing, extending, or rotating the involved 
joint.
• Generally a weight-bearing lameness.
• Joint effusion with capsular distention—
common with OCD of elbow, stifle, and 
hock.
• Muscle atrophy—consistent finding with 
chronic lameness.
• Hock OCD—hyperextension of the 
tarsocrural joint.
CAUSES
• Diet containing 3 times the recommended 
calcium levels.
• Overfeeding.  DIAGNOSIS
• Soft tissue trauma.
• Intra-articular (osteochondral) fractures.
N/A
N/A
IMAGING
• Standard craniocaudal and mediolateral 
views—necessary for all involved joints.
• Failure of normal endochondral ossification 
results in radiolucency. Thus the normal bone 
contour is lost, which radiographically 
appears as flattening of the subchondral bone 
or as a subchondral lucency.
• Cannot be differentiated from OCD on 
plain radiographs unless the cartilage flap is 
mineralized.
• Sclerosis of the underlying bone—common 
in chronic OCD lesions.
• Calcified bodies within the joint (joint 
mice)—indicate dislodged cartilage flap.
• Contralateral joint—comparison; check for 
• Oblique views—may improve visualization, 
especially for hock, elbow, and shoulder lesions.
• Skyline views of the talar ridges of the hock 
joint—help identify medial and lateral lesions.
CT and MRI
Useful for visualizing extent of subchondral 
lesions. MRI is the most accurate method of 
detecting osteochondrosis/OCD lesions, 
flaps, and fragments.
Can be used to detect lesions, but is very 
operator dependent and is the least accurate 
diagnostic imaging method.
Positive Contrast Arthrography
Useful for differentiating OCD of the 
shoulder from other conditions.
• Diagnosis most frequently made based on 
physical examination and diagnostic imaging.
• Arthrocentesis and analysis of synovial 
fluid—confirms involvement; should note 
straw-colored fluid with normal to decreased 
viscosity; from cytology, should note >90% 
mononuclear cells. Not specific for osteo  - 
chondrosis.
• Arthroscopy—minimally invasive; excellent 
method for differentiating from OCD and 
for therapeutic treatment.

1008  Blackwell’s Five-Minute Veterinary Consult  
OPATHOLOGIC FINDINGS
• Articular cartilage—initially may appear 
yellowish.
• Retention of articular cartilage extending 
into subchondral bone surrounded by 
increased amount of trabecular bone.
• Clefts between the underlying subchondral 
bone and the degenerated and necrotic deep 
layer of the overlying thickened (retained) 
cartilage.
  TREATMENT
N/A
• Cryotherapy (ice packing) of affected 
joint—immediately post-surgery; 5–10 
minutes q8h for 3–5 days.
• Range-of-motion exercises—initiated as 
soon as patient can tolerate.
ACTIVITY
• Restricted.
• Avoid hard concussive activities (e.g., 
running on concrete).
DIET
Weight control—important for decreasing 
load and, therefore, the stress on the affected 
joint(s).
• Discuss the heritability of the disease.
• Warn client that osteoarthritis is likely to 
develop.
• Discuss the influence of excessive intake of 
• Osteochondrosis of articular cartilage is 
generally a nonsurgical condition..
• May progress to OCD as the patient grows. 
If OCD develops, surgery is generally 
• Surgery is performed by arthrotomy or 
arthroscopy, and is indicated for most 
patients with OCD.
• Surgical treatment usually involves removal 
of the cartilage flap and subchondral bone 
debridement.
• Osteochondral autografts have been 
described for treatment of OCD of the 
caudal humeral head, medial aspect of 
the humeral condyle, and femoral 
condyles. Benefit beyond surgical 
debridement by flap removal requires 
further investigation.
• Synthetic osteochondral implants are 
available for resurfacing and have been 
described for use in the stifle joint of dogs.
• Shoulder—indicated for all OCD lesions; 
exploratory procedure indicated for pain and 
lameness with radiographic evidence of 
osteochondrosis.• Elbow—indicated for all OCD lesions; 
indicated to assess for other conditions (see 
Elbow Dysplasia).
• Stifle—controversial; patients develop 
osteoarthritis even with procedure; arthroscopy 
may improve the recovery rate and long-term 
function.
• Hock—remove osteochondral flap; 
controversial; all patients develop severe 
osteoarthritis even with procedure. 
Arthrodesis is considered an option for 
patients with severe disease.
• Sacrum—remove fragment if impinging on 
the cauda equina.
(NSAIDs) and analgesics—may be used to 
symptomatically treat osteoarthritis associated 
with OCD; does not promote healing of the 
cartilage flap (thus surgery is still indicated).
Avoid corticosteroids owing to potential side 
effects and articular cartilage damage 
associated with long-term use.
patients.
N/A
glycosaminoglycans, green-lipped mussel 
extract, and glucosamine/chondroitin sulfate)—
may help limit cartilage damage and degenera -
tion; may help alleviate pain and inflammation.
  FOLLOW-UP
• Periodic monitoring until patient is 
skeletally mature—recommended to assess 
progression to an OCD lesion.
• Post-surgery for OCD—limit activity for 
4–6 weeks; encourage early, active movement 
of the affected joint(s).
• Yearly examinations—recommended to 
assess progression of osteoarthritis.
• Discourage breeding of patients.
• Restricted weight gain and growth in young 
dogs—may decrease incidence.
• Shoulder—good to excellent prognosis for 
return to full function; minimal osteoarthritis 
development with osteochondrosis and after 
OCD surgery.
• Elbow, stifle, and hock—fair prognosis for 
osteochondrosis, guarded for OCD; depends 
on size of lesion (most important), 
osteoarthritis, and age at diagnosis and 
treatment; progressive osteoarthritis 
development, even after surgery.
• Sacrum—good after cartilage fragment 
removal.
N/A
N/A
N/A
N/A
SEE ALSO
Elbow Dysplasia.
drug.
• OCD = osteochondritis dissecans.
Breur GJ, Lambrechts NE. Osteochondrosis. 
In: Johnston SA, Tobias KM, eds., 
Veterinary Surgery Small Animal, 2nd ed. 
St. Louis, MO: Elsevier Saunders, 2018, 
pp. 1372–1385.
Egan P , Murphy S, Jovanovik J, et al. 
T reatment of osteochondrosis dissecans of 
the canine stifle using synthetic 
osteochondral resurfacing. Vet Comp 
Orthop T raumatol 2018, 31(2):144–152.
Kuroki K, Cook JL, Stoker AM, et al. 
Characterizing osteochondrosis in the dog: 
Potential roles for matrix metalloproteinases 
and mechanical load in pathogenesis and 
disease progression. Osteoarthritis Cartilage 
2005, 13(3):225–234.
Wall CR, Cook CR, Cook JL. Diagnostic 
sensitivity of radiography, ultrasonography, 
and magnetic resonance imaging for 
detecting shoulder osteochondrosis/
osteochondritis dissecans in dogs. Vet 
Radiol Ultrasound 2015, 56(1):3–11.
available onlineOsteochondrosis  (continued)

Canine and Feline, Seventh Edition  1009
O
Osteomyelitis
  BASICS
Acute or chronic inflammation of bone, 
usually caused by bacteria. Less common 
causes include fungi, parasites, viruses, foreign 
bodies, and corrosion of metallic implants.
• Direct inoculation of bone with pathogenic 
bacteria—most common route of infection. 
May not initiate infection unless local tissue 
environment is affected (e.g., poor vascularity, 
necrotic bone or soft tissue, sequestration, 
altered tissue defenses or systemic immune 
response, foreign material, or surgical implants). 
• Hematogenously disseminated microorganisms 
from a distant site in the body localize in the 
metaphyseal region of long bones in young 
animals and vertebrae of adults. Inflammation 
and thrombus formation produce an ischemic 
environment that promotes bacterial 
proliferation. Mycotic infections are often due 
to hematogenous dissemination of inhaled 
spores. • Extension of soft tissue infections to 
bone—uncommon in small animals. • Biofilm 
formation protects bacteria from phagocytes, 
antibacterials and antibodies.
GENETICS
Breeds with heritable immunodeficiency or 
hematogenous diseases.
• Hematogenous disease—rare. • Prevalence 
of fracture-associated osteomyelitis—radius/ulna 
41.5%; femur 28.5%. • Discospondylitis in 
adult dogs and cats and fungal disease—not 
uncommon.
• Actinomycosis—migrating grass awns can 
cause soft tissue infections, which may extend 
to bone. • Blastomycosis—central and 
eastern regions of the United States, Canadian 
provinces of Quebec, Manitoba, and Ontario. 
• Coccidioidomycosis—southwestern United 
States, Mexico, and Central and South 
America. • Histoplasmosis—Ohio, Missouri, 
and Mississippi river valleys.
Species
Breeds with immunodeficiency and hematog-
enous diseases.
Hematogenous metaphyseal infection—
immature dogs.Predominant Sex
Male dogs—for post-traumatic infection; 
SIGNS
• Acute postoperative wound infections after 
orthopedic surgery—may be indistinguishable 
from acute condition; may progress to chronic 
disease. • Most patients have chronic disease 
at time of examination and diagnosis.
• Lameness. • Draining tracts. • Previous 
trauma. • Fracture or surgery. • Hind limb 
weakness and difficulty in rising—disco -
spondylitis or vertebral osteomyelitis. • T ravel 
to regions endemic for mycotic infections.
• Acute hematogenous disease (dogs)—
sudden onset of systemic illness; soft tissue 
swelling over affected site; lameness; pyrexia; 
lethargy; limb pain. • Chronic condition—
localized disease, usually no systemic 
component; chronic draining tracts, pain, 
muscle atrophy, muscle contracture. 
• Infected non-union fracture—instability, 
crepitus, limb deformity. • Bone infections of 
the spine—pain and neurologic deficits.
CAUSES
• T rauma or orthopedic surgery. • Penetrating 
foreign body. • Extension to bone of soft tissue 
infection—periodontitis; rhinitis; otitis media; 
paronychia. • Hematogenous infection. 
• Staphylococcus pseudintermedius  common—
almost 50% are methicillin-resistant strains; 
often monomicrobial infection. Polymicrobial 
infections are common—may include 
Gram-negative organisms: E. coli , Pasteurella , 
Serratia , Pseudomonas , Proteus , and Klebsiella  
spp. • Anaerobic bacteria— Actinomyces , 
Clostridium , Peptostreptococcus , Bacteroides , 
Nocardia  and Fusobacterium . • Fungal 
infection —Coccidioides , Blastomyces , 
Histoplasma , Candida , Cryptococcus , and 
Aspergillus  species.
• Open fracture. • Soft tissue trauma. 
• Penetrating wounds. • Migrating foreign 
body. • Orthopedic surgery/implants. 
• Cortical bone allograft. • Immunodeficiency. 
• Nosocomial infection.
  DIAGNOSIS
• Panosteitis. • Neoplasia. • Bone cysts. 
• Delayed fracture union due to instability. 
• Hypertrophic osteodystrophy. 
• Hypertrophic osteopathy. • Medullary 
bone infarction.CBC/BIOCHEMISTRY/URINALYSIS
• Hemogram—neutrophilia ± left shift with 
acute disease. • Fungal hyphae may be 
present in the urine of systemically ill patients 
with aspergillosis.
• Serology—confirms some fungal infections. 
• Blood cultures if hematogenous infection 
suspected. • Urine excretion of antigen for 
IMAGING
• Acute disease—bone architecture normal; 
soft tissue swelling; gas may be evident if 
anaerobic infection. • Chronic disease—
sequestrum (avascular segment of bone); 
periosteal new bone formation; involucrum 
formation (reactive bone surrounding 
sequestrum); bone resorption—widening of 
fracture gaps; cortical thinning; generalized 
osteopenia; implant loosening. 
• Fistulogram—can help identify sequestra or 
radiolucent foreign bodies.
Other
• Ultrasonography—localize large fluid 
accumulations for needle aspiration or foreign 
bodies. • Contrast CT or MRI identification 
of sequestra, foreign material. 
• Scintigraphy—uncommonly available and 
• Fluid aspirates of fluctuant areas or Jamshidi 
needle tissue biopsies for aerobic and anaerobic 
culture and in vitro  antimicrobial drug 
susceptibility—collect by sterile techniques. 
• Open surgical biopsy—indicated when 
needle aspirates are negative or when 
debridement is necessary for treatment; culture 
samples of necrotic tissue, sequestra, implants, 
and foreign material; histopathologic exam -
ination for suspected fungal infection and to 
rule out neoplasia. Request special fungal stains 
on pathology samples. • Samples for anaerobic 
culture—immediately place into appropriate 
transport medium. Avoid culturing purulent 
fluid from draining tracts—results misleading 
as often get contaminants from skin. • Blood 
cultures—indicated in acute hematogenous 
osteomyelitis or chronic disease with 
septicemia. • Urine culture to rule out urinary 
tract infection as a source for hematogenous 
disease.
• Bone sequestration—virtually diagnostic.
• Inflammation and necrosis of bone and the 
adjacent tissues. • Cytologic or histopathologic 
examination of smears or sections—can be 
helpful for identification of pathogenic organisms 
(especially fungal hyphae).

1010  Blackwell’s Five-Minute Veterinary Consult  
• Inpatient—surgical debridement, drainage, 
culturing, irrigation, and wound management 
until infection begins to resolve; infected 
fractures (surgical stabilization). 
• Outpatient—long-term oral antimicrobial 
• Depends on severity, location, and degree 
of associated soft tissue injury. • Avoid 
pathogen contamination to other patients. 
• Physical rehabilitation therapy.
ACTIVITY
Restricted—to prevent pathologic fracture; 
with an unhealed fracture.
DIET
• Warn the client about cost of treatment, 
likelihood of recurrence, possibility of 
repeated surgical intervention, and long 
duration of therapy. • Discuss prognosis.
• Chronic disease—surgical debridement; 
sequestrectomy; establish drainage. • Infected 
stable fracture—leave preexisting implants in 
place during healing. • Infected unstable 
fracture—remove implants; stabilize with 
external or internal skeletal fixation. • Bone 
deficits—graft with autologous cancellous 
bone either acutely or after infection has 
abated and granulation tissue is present. 
• Large segmental deficits in long bones—
bone regeneration by bone transport utilizing 
the Ilizarov technique or other bone segment 
transport mechanism. • Localized chronic 
infection—consider amputation or en bloc  
resection and primary wound closure. 
• Remove all implants after the fracture has 
healed to eliminate biofilm. • Muscle flap 
coverage of exposed bone early in the course 
of treatment greatly reduces contamination of 
bone and promotes fracture healing.
• Administer a broad-spectrum bactericidal 
antimicrobial intravenously for 3–5 days while 
awaiting culture and susceptibility results, 
then switch to appropriate antimicrobial which must be given for 4–8 weeks; continue 
for at least 2 weeks beyond radiographic and 
clinical resolution of infection. • S. 
pseudintermedius— amoxicillin–clavulanate, 
cefazolin, oxacillin are reasonable empirical 
choices. • Antibiotics effective against 
anaerobes that are also available for parenteral 
administration—ampicillin sodium, 
metronidazole, clindamycin. 
• Aminoglycosides and quinolones—effective 
against Gram-negative aerobic bacteria. 
• Quinolones—may give orally; not 
nephrotoxic; to protect against resistance, use 
only for infections caused by Gram-negative 
organisms that are resistant to other oral 
antimicrobial drugs. • Chronic disease—
continuous local delivery of antimicrobial 
drugs by antibiotic-impregnated bone cement 
(beads) or biodegradable material (gels). 
• Fungal osteomyelitis—long-term therapy 
(months); treat at least a month beyond 
resolution of clinical signs; e.g., itraconazole 
5–10 mg/kg PO q24h; given continuously 
may control disseminated aspergillosis long-  
term. • Analgesics— important to encourage 
limb use.
Quinolones— potential for cartilage injury in 
immature dogs.
Aminoglycosides—may cause nephrotoxicity.
Identify other antimicrobial drugs by 
repeating cultures and susceptibility 
determination if the infection becomes 
unresponsive to the initial agent.
  FOLLOW-UP
• Radiography—2–3 weeks after intervention 
and then every 4–6 weeks to monitor bone 
healing. • Reculture bone—suspected 
persistent infection.
N/A
• Recurrence. • Progression to chronic 
disease. • Malignant neoplasia—rare sequela 
to chronic infection of fractures repaired by 
internal fixation.
• Acute infection—may be cured by 4–8 
weeks of antimicrobial drug therapy if there is 
limited bone necrosis and no fracture. • Chronic disease—resolution with 
antimicrobial drug therapy alone unlikely; 
provide appropriate surgical treatment. 
• Recurrence of chronic infection may 
require repeated sequestrectomy. • Consider 
amputation in severe chronic cases with 
irreversible loss of limb function.
N/A
N/A
Pets with multidrug-resistant bacterial 
infections can shed organisms that can 
colonize humans.
N/A
SYNONYMS
Bone infection.
SEE ALSO
Fossum TW. Other diseases of bones and 
joints: osteomyelitis. In: Small Animal 
Mosby, 2013, pp. 1407–1410.
Greene CE, Bennett D. Musculoskeletal 
Diseases of the Dog and Cat, 4th ed. St. Louis, 
MO: Saunders Elsevier, 2012, pp. 892–902.
Inzana JA, Schwarz EM, Kates SL, Awad HA. 
Biomaterials approaches to treating 
implant-associated osteomyelitis. 
Biomaterials 2016, 81:58–71.
Robinson D. Osteomyelitis and implant-
associated infections. In: Johnston SA, 
2017, pp. 775–783.
Sykes JE, Kapatkin AS. Osteomyelitis, 
discospondylitis, and infectious arthritis. In: 
2013, pp. 814–829.
Author  Tisha A.M. Harper
available onlineOsteomyelitis  (continued)

Canine and Feline, Seventh Edition  1011
O
Osteosarcoma
  BASICS
Osteosarcoma (OS) is a cancer derived from a 
malignant osteoblast cell lineage within the 
endosteum, and is the most common primary 
bone tumor in dogs. Large- to giant-breed 
dogs most commonly develop appendicular 
OS, while axial OS tends to affect smaller 
breeds (<15 kg). The biologic behavior of OS 
is aggressive locally and distantly, with 
presumed microscopic lung metastases 
present in ≥85% of dogs at diagnosis. OS is 
rare in cats, and the biologic behavior is less 
malignant than in dogs.
Genetic predisposition is likely a major 
contributor for the development of OS. 
Other factors contributing include chronic 
inflammation associated with metallic 
implants, history of prior radiation therapy to 
the site of tumorigenesis, and rapid bone 
turnover, all associated with the development 
of OS in dogs.
• Musculoskeletal—the appendicular 
skeleton (metaphyseal region of long bones) is 
most commonly affected in dogs. OS may 
also occur in the axial skeleton.
• Respiratory—the most common metastatic 
site is the lung parenchyma; however, other 
sites include bones, regional lymph node, 
skin, and visceral organs (liver, kidney).
GENETICS
There is a strong breed predilection, with 
some degree of heritability being identified in 
giant breeds such as Scottish deerhound, 
Rottweiler, greyhound, and Irish wolfhound.
• Dogs—OS accounts for up to 85% of 
primary bone tumors in dogs, representing 
~5% of all reported malignancies in dogs.
• Cats—OS is the most common primary 
bone tumor in cats, accounting for <7% of all 
reported cancers in this species.
Species
• Dogs—large to giant breed (>40 kg).
• Cats—domestic shorthair cats.
• Dogs—bimodal peak at 2 years and 7 years, 
reported to occur as young as 6 months.
• Cats—average age 8.5 years (range 4–18 years).
Dogs and cats—no strong sex predilection.SIGNS
• Because OS occurs most commonly in the 
appendicular skeleton of dogs and cats, 
lameness and pain are common clinical 
findings.
• Clinical symptoms associated with OS 
affecting the axial skeleton can be variable 
depending upon the anatomic site involved.
• Lameness (acute or chronic) is the most 
common presenting clinical sign.
• Signs of axial skeletal OS vary, depending 
on the site of the lesion.
• A firm, painful swelling of the affected site 
is common with either appendicular or axial 
skeletal OS.
• Degree of lameness varies from mild to 
non-weight-bearing.
• Soft tissue swelling secondary to tumor 
CAUSES
Unknown in both species.
• Dogs—large- to giant-breed dogs at greater 
risk.
• Metallic implants at fracture repair sites.
• Exposure to ionizing radiation.
• Cats—unknown.
  DIAGNOSIS
• Other primary bone tumor (i.e., fibrosarcoma, 
chondrosarcoma).
• Metastatic bone tumor (i.e., prostatic, 
mammary, other carcinoma).
• Infectious (i.e., fungal or bacterial 
osteomyelitis).
Elevated alkaline phosphatase is a poor 
prognostic factor.
IMAGING
Radiography of Primary Site
• At least two views of the primary lesion 
should be acquired.
• Radiographic findings include mixed 
osteolytic/osteoproductive effects involving 
the affected skeletal site.
• Soft tissue swelling overlying diseased bone.
• Three-view thoracic radiographs should be 
performed; although visible macroscopic 
metastatic disease is present in <10% of cases 
at the time of presentation.
• Pulmonary metastases at initial diagnosis is 
associated with an extremely poor prognosis.• Metastatic lesions typically appear as 
discrete, round, soft tissue density nodules.
OTHER DIAGNOSTIC PROCEDURES
Bone Aspirate
• A relatively noninvasive, high-yield 
procedure using an 18-gauge needle to collect 
OS cells from the diseased skeletal site.
• Cytology can provide a diagnosis of 
malignant mesenchymal neoplasia.
• Concurrent alkaline phosphatase positivity 
on cytology is sensitive and specific for OS 
Bone Biopsy
• Performed with the patient under light 
general anesthesia or moderate sedation.
• Samples should be taken through the center 
of the lesion; peripheral biopsies are often 
nondiagnostic and contain reactive osteoblasts.
• Biopsy may be performed using a Michele 
trephine, Jamshidi bone biopsy needle, or 
open biopsy technique.
• Gross—moderate to severe destruction of 
cortical bone with new bone proliferation.
• Histologic—malignant population of 
mesenchymal cells that are plump, polygonal 
to spindyloid in shape. The finding of osteoid 
production is necessary and diagnostic for OS.
  TREATMENT
DIET
No specific dietary management is required, 
although weight loss may benefit amputees in 
general.
• Long-term prognosis is poor; however, a 
subpopulation (15%) of patients achieve 
long-term survival (>2 years).
• Clients must understand that treatment 
goals are to relieve discomfort and prolong 
life; a cure is unlikely.
Dogs—Appendicular Sites
• Surgical management involves amputation 
of the affected limb.
• Limb salvage therapy is available at a 
limited number of referral hospitals. This 
technique is appropriate only for locally 
confined and small distal radial lesions. The 
primary tumor is surgically removed, replaced 
by a commercially available metal 
endoprosthesis with modified bone plate.
Dogs—Axial Sites
• Depending on location, aggressive surgical 
excision or radiation therapy, in conjunction 
with adjuvant chemotherapy are 

1012  Blackwell’s Five-Minute Veterinary Consult  
O• If surgical resection is not possible, 
palliative radiation is effective for the 
alleviation of osteolytic bone pain.
Cats—Appendicular Sites
• Amputation alone is considered 
• Adjuvant chemotherapy not necessary.
Cats—Axial Sites
• Depending on site of lesion, aggressive 
surgical excision or radiation therapy should 
be instituted.
• Local recurrence appears to be the main 
reason for treatment failure.
Metastatectomy
• Pulmonary metastatectomy has been 
described for dogs with OS; however, is not 
routinely practiced.
• Selection criteria for dogs to undergo this 
procedure include a long disease-free interval 
(>300 days) and only 1–2 pulmonary nodules 
based on thoracic radiographs.
Inoperable Neoplasms
• Palliative (coarse fractionation) 
radiotherapy or stereotactic radiosurgery 
combined with systemic chemotherapy and 
aminobisphosphonate therapy can provide 
prolonged survival times with acceptable pain 
control (10–12 months).
• Pain management with nonsteroidal 
anti-inflammatory drugs, opioids, and/or 
bisphosphonates may improve quality of life 
and thus prolong survival.
Definitive Therapy
• Chemotherapy with either platinum-based 
drugs (cisplatin or carboplatin) or doxorubicin 
is the current standard of care; a minimum of 
four doses is recommended.
• Cisplatin 70 mg/m2 IV q3 weeks. Must be 
given with a saline-induced diuresis to 
prevent nephrotoxocity: 18.3 mL/kg/h for 
4 hours, administer chemotherapy over 20 
minutes, then continue diuresis for another 
2 hours. Antiemetics must be given before 
cisplatin, and the patient may need to be sent 
home with antiemetic therapy.
• Carboplatin 300 mg/m2 IV q3 weeks.• Doxorubicin 30 mg/m2 IV q3 weeks for 
5 doses.
• Chemotherapy or toceranib phosphate 
(Palladia) is not effective against gross disease; 
less than 5% expected response rate.
• Chemotherapy typically initiated within 
2 weeks of surgery.
• Patients with preexisting renal dysfunction 
should not be treated with platinum-based 
chemotherapy drugs.
• Do not give cisplatin to cats.
Palliative Therapy
• Pain management must be addressed in 
patients whose owners decline definitive 
therapy.
• Manage pain with nonsteroidal anti-
inflammatory drugs, ± tramadol (2–5 mg/kg 
q8–12h), ± acetaminophen with codeine 
(0.5–2 mg/kg q8–12h), ± transdermal 
fentanyl (as per package instructions) ± 
gabapentin (3–10 mg/kg q8–24h).
• Euthanasia when quality of life declines.
  FOLLOW-UP
• Monitor CBC for evidence of myelo -
suppression 7–14 days following 
• Doxorubicin—periodic echocardiography 
and ECGs as cumulative cardiotoxicity may 
occur at >180 mg/m2.
• Three-view thoracic radiographs every 2–3 
months after surgery to assess for metastasis.
• Metastatic disease is very likely; sites of 
spread include lungs, other bones, soft tissue.
• Animals that undergo limb salvage may 
develop recurrent infections, local recurrence, 
or implant failure.
• Animals treated with systemic chemo -
therapy can develop adverse side effects, 
including bone marrow suppression and 
gastrointestinal upset. Symptomatic 
management is typically effective, however, 
life-threatening complications can occur 
infrequently.EXPECTED COURSE AND PROGNOSIS
Dogs
• Without treatment, with amputation alone, 
or with palliative radiotherapy alone, median 
survival is approximately 4 months. When 
conventional palliative radiotherapy is 
combined with IV aminobisphosphonates 
and oral analgesics, acceptable quality of life 
can be extended up to 6–9 months. The use 
of stereotactic radiosurgery in combination 
with chemotherapy and aminobisphosphonates 
can extend survival times to 10–12 months.
• With surgery and chemotherapy, median 
survival is extended to a median of 10 months.
Cats
• Appendicular OS, with surgery, median 
survival of >2 years.
• Axial OS, with surgery, median survival of 
5.5 months.
Do not breed animals that are undergoing 
SYNONYMS
Osteogenic sarcoma.
SEE ALSO
• Hemangiosarcoma, Bone.
• OS = osteosarcoma.
Ehrhart NP , Ryan S, Fan TM. T umors of 
the skeletal system. In: Withrow and 
MacEwen’s Small Animal Clinical 
Oncology, 5th ed. St. Louis, MO: Elsevier, 
pp. 463–503.
Author  Timothy M. Fan
available onlineOsteosarcoma  (continued)

Canine and Feline, Seventh Edition  1013
O
Otitis Externa and Media
  BASICS
• Otitis externa—inflammation of the 
external ear canal; includes anatomic 
structures of the pinna, horizontal and 
vertical canals, and the external layer of the 
tympanic membrane.
• Otitis media—inflammation of the middle 
ear; includes anatomic structures of the 
tympanic membrane, bulla (tympanic cavity), 
auditory ossicles, and auditory tube.
• Otitis externa—chronic inflammation 
results in alterations in the environment of 
the canal; with inflammation, cerumen glands 
enlarge and produce excessive wax; the 
epidermis and dermis thicken and become 
fibrotic; thickened canal folds reduce canal 
width; calcification/ossification of auricular 
cartilage is the end-stage result.
• Otitis media—often an extension of otitis 
externa through the tympanic membrane 
(dogs); a result of infection ascending through 
the auditory tube to the middle ear (cats). 
Chronic viral upper respiratory infection early 
in life may change the ability of the auditory 
tube to protect the bulla from infection. 
Otitis media can occur from polyps or 
neoplasia within the middle ear or auditory 
tube.
• Nervous.
Environmental humidity may predispose to 
Species
• Pendulous-eared dogs—especially spaniel 
and retriever.
• Dogs with hirsute external canals—terrier 
and poodle.
• Stenosis of the external ear canal—pug and 
bulldog; stenosis of the external orifice of ear 
canal—shar pei.
• Primary secretory otitis media—cavalier 
King Charles spaniel.
SIGNS
• Pain—shying from touching of the head, 
refusing to open the mouth, dropping food.
• Head shaking.
• Scratching at the pinnae.
• Malodor from canals.
• Peripheral vestibular deficits or facial 
paralysis or paresis.Physical Examination Findings
Otitis Externa
• Inflammation, pain, pruritus, and erythema 
of the pinnae and external canals.
• Stenosis of external orifices and/or ear 
canals.
• Deafness from obstruction.
• Purulent and malodorous exudates.
• Aural hematoma.
• Palpable scarring and calcification of the 
auricular cartilage.
• Holding of the pinna down and/or head tilt 
toward the affected side (if unilateral).
Otitis Media
• Vestibular signs—ipsilateral facial nerve 
paralysis and/or Horner’s syndrome; 
uncommon in the cat, more common in the 
dog.
• Intact tympanic membrane—bulging pars 
flaccida.
• Evidence of fluid and/or gas behind the 
pars tensa; membrane may be opaque; fluid 
may be purulent or hemorrhagic.
• Ruptured tympanic membrane—discharge 
into canal or bullae filled with debris.
• Deafness (otitis media progressing to otitis 
interna).
• Pain on palpation or opening of the mouth.
• Xeromycteria (uni- or bilateral nasal 
planum hyperkeratosis—lack of nasal 
secretion due to parasympathetic nerve 
dysfunction).
CAUSES
• Predisposing factors—present prior to the 
development of ear disease:
◦ Conformation (see Breeds).
◦ Excessive moisture (high humidity, 
swimming).
◦ Obstructive ear disease (neoplasia, polyp).
◦ Primary otitis media.
• Perpetuating factors—changes in anatomy 
or physiology in response to otitis externa:
◦ Altered wax migration, excessive 
production of debris.
◦ Proliferative changes, stenosis.
◦ Calcification.
• Primary causes—directly initiate or cause 
inflammation within the ear canal:
◦ Parasites— Otodectes cynotis , Demodex  
spp., Otobius megnini , chiggers.
◦ Hypersensitivities—atopy, food, contact; 
recurrent otitis externa may be the only 
clinical sign of hypersensitivity.
◦ Foreign bodies—plant awns.
◦ Keratinization disorders and increased 
cerumen production.
◦ Endocrinopathy—immune-mediated; 
drug reaction (topical or systemic).
• Secondary causes—create disease in an 
abnormal ear:
◦ Bacterial or yeast infection.
◦ Excessive moisture and maceration 
(overcleaning, trauma).
◦ Topical irritants.  DIAGNOSIS
• Strict diet trial to diagnosis cutaneous 
adverse reaction to food.
IMAGING
• Bullae radiographs—may be normal; bullae 
may appear cloudy if filled with exudate; 
thickening of bulla and petrous temporal 
bone with chronic disease; presence of bone 
lysis with osteomyelitis or neoplastic disease.
• CT or MRI—detailed evidence of fluid or 
tissue density in the bulla, adjacent tissues, or 
auditory tube.
• Otoscopy or video-otoscopy—visualization 
of the external canal, tympanic membrane, 
and portions of the bulla (if tympanum 
ruptured).
• Cytologic examination of exudate—most 
important diagnostic tool after complete 
examination of the ear canal; otic discharge 
sample should be taken before cleaning or 
treatment are initiated; examine exudates 
from each ear canal:
◦ Morphologically describe and quantitate 
bacteria, yeast, inflammatory cells (0 to 4+ 
scale) for treatment monitoring.
◦ Type(s) of bacteria or yeast—assist in the 
choice of therapy .
• Infections within the canal can change with 
prolonged or recurrent therapy; repeat 
cytology is required in chronic cases.
• Myringotomy—spinal needle or sterile 
catheter is inserted through the tympanic 
membrane to sample fluid within the bulla 
for cytologic examination and culture.
• Culture of otic exudate—recommended in 
cases of otitis media and/or persistent 
• Parasites— Otodectes , Otobius , and chiggers 
are visualized on otoscopy; Demodex  can be 
diagnosed on ear cytology.
  TREATMENT
Demonstrate proper method for cleaning and 
medicating ears (e.g., volume of medication 
to instill).
• Lateral ear resection—disease affects 
primarily the vertical canal.
• Total ear ablation—entire canal is severely 
stenotic and oral glucocorticoids have failed 
to decrease stenosis or proliferative changes; 
tympanic bulla is diseased; or neoplasia affects 
the canal.

1014  Blackwell’s Five-Minute Veterinary Consult  
Cleansing Solutions
• Tympanum integrity should be assessed 
prior to introduction of solutions and/or 
medications into the external ear canal.
• At home cleaning:
◦ Cleanser/dryer 2–3 times a week for mild 
to moderate amounts of wax. Combination 
cleanser/drying products—contain 
ceruminolytics (e.g., docusate sodium or 
dioctyl sodium sulfocuccinate, propylene 
glycol), drying agents (e.g., dimethicone), 
germicidals (e.g., acetic acid, boric acid)—
contraindicated in cases of perforated 
◦ Acetic acid 5% (white vinegar) diluted 
1:2 in water—good activity against bacteria 
including Pseudomonas , and yeast. Safe in 
middle/inner ear.
◦ T ris-EDTA—antibacterial activity; 
enhances susceptibility of bacteria to 
various antibiotics. Low ototoxic potential; 
safe in middle ear.
◦ Chlorhexidine—antiseptic, concentrations 
of less than 0.2% are safe within the 
middle ear.
◦ N-Acetylcysteine—antimicrobial and 
mucolytic properties, and ability to disrupt 
bacterial biofilm.
• “In clinic” cleaning on awake animals:
◦ Bulb syringe or trimmed French red 
rubber catheter used to flush in solution 
◦ Deep ear cleaning with general anesthesia 
when needed.
Systemic Antibiotics (Indications)
• Severe otitis and neutrophils are seen on 
cytology suggesting a deeper infection.
• Otitis media.
• Best chosen by culture and sensitivity 
test—empiric choices include cephalexin 
30 mg/kg q12h, amoxicilin+clavulanic acid 
13.75 mg/kg q12h, clindamycin 11 mg/kg 
q12h when cocci are seen cytologically; 
marbofloxacin 2.75 mg/kg q24h if rods are 
seen cytologically.
Systemic Antifungals (Indications)
• Refractory Malassezia  infection or when 
owners are unable to apply topical treatment.• Otitis media caused by Malassezia  or other 
fungal organism.
• Dogs—ketoconazole 5–10 mg/kg q24h, 
terbinafine 20–30 mg/kg q24h.
• Cats—itraconazole 5 mg/kg q24h.
Systemic Glucocorticoids (Indications)
• Reduce inflammation and cerumen 
production associated with otitis externa.
• Reduce proliferative changes secondary to 
inflammation in ear canals.
• Starting dosages—prednisolone 1 mg/kg/day, 
dexamethasone 0.1 mg/kg/day, triamcinolone 
0.1 mg/kg/day; higher dosages can be used for 
more severe inflammatory changes.
• Antiparasitic therapy against mites—
avermectins, isoxazolines.
• Otobius  (ear tick) should be removed from 
inside the ear canal.
Topical
• Continue cleanings until symptoms resolve 
and then routinely to maintain control.
• Apply appropriate topical medications in 
sufficient quantity to completely treat the 
entire canal: Amount used is determined by 
the size of ear—instilled once or twice daily.
• Antibiotic—based on cytologic evaluation 
and/or empiric choice. Gentamicin, neomycin—  
cocci infection; enrofloxacin and silver 
sulfadiazine—rods; amikacin—resistant 
Pseudomonas .
• Antifungal (anti- Malassezia )—clotrimazole, 
ketoconazole, miconazole, thiabendazole, 
nystatin, terbinafine; posaconazole—
refractory Malassezia  cases.
• Anti-inflammatory (glucocorticoid)—
dexamethasone, fluocinolone, betamethasone, 
triamcinolone, hydrocortisone aceponate, and 
mometasone.
• Antiparasitic—ivermectin and thiabendazole.
• Ruptured tympanum—use caution with 
topical cleansers other than sterile saline or 
dilute acetic acid; potential for ototoxicity; 
• Ivermectin—non-FDA approved for use 
systemically; herding (dog) breeds have increased 
sensitivity ( MDR1 /ABCB1  gene mutation).
• Use caution when cleaning the external ear 
canals of all animals with severe and chronic 
otitis externa; the tympanum can easily rupture.
• Post-flushing vestibular complications are 
more common in cats, although usually temporary; warn clients of possible 
complications and residual effects.
Topical medications infrequently induce 
contact irritation or allergic response; 
reevaluate all worsening cases.
  FOLLOW-UP
Cytology of ear canals should be repeated at 
each clinic visit.
• Routine ear cleaning at home.
• Control of underlying diseases.
Deafness, vestibular disease, cellulitis, facial 
nerve paralysis, progression to otitis interna, 
and rarely meningoencephalitis.
• Otitis externa—with proper therapy, most 
mild initial cases resolve in 3–4 weeks; failure 
to correct underlying primary cause results in 
• Otitis media—requires at least 6 weeks of 
systemic antibiotics until all signs resolve.
• Osteomyelitis of petrous temporal bone and 
bulla—may require 6–8 weeks of antibiotics.
• Vestibular signs may improve within 2–6 
weeks; some animals may have residual 
symptoms.
FL: CRC Press, 2017, pp. 1–223.
Resnick
available onlineOtitis Externa and Media  (continued)

Canine and Feline, Seventh Edition  1015
O
Otitis Media and Interna
  BASICS
Inflammation of the middle (otitis media) 
and inner (otitis interna) ears, commonly 
caused by bacterial infection.
• Media—from extension of infection of the 
external ear through the tympanic membrane; 
may extend from the oral and nasopharyngeal 
cavities via the eustachian tube. • Interna—
may also result from hematogenous spread of 
a systemic infection.
Nervous
• Impaired balance due to damage to the 
vestibular apparatus in the inner ear or to the 
vestibular portion of vestibulocochlear nerve. 
• Nausea from dizziness due to impaired 
balance. • Hearing loss due to damage to hair 
cells in the cochlea or to the cochlear portion 
of vestibulocochlear nerve. • CNS signs when 
spread of infection intracranially (otogenic 
intracranial infection).
• Keratoconjunctivitis sicca (KCS; dry eye)—
from damage to parasympathetic branch of the 
facial nerve supplying the lacrimal gland. 
• Corneal ulcer—as a consequence of inability 
to blink due to damage to facial nerve or from 
KCS. • Horner’s syndrome—from damage to 
sympathetic nerve as they course through the 
middle ear.
• Dogs more often affected than cats. 
• Cocker spaniels and other long-ear breeds. 
• Poodles with chronic otitis or pharyngitis 
from dental disease. • Primary secretory otitis 
media in cavalier King Charles spaniels.
SIGNS
• Pain when opening the mouth; reluctance 
to chew; shaking the head; pawing at the 
affected ear. • Vestibular deficits, which may 
be persistent, transient, or episodic. 
• Unilateral involvement causes head tilt, 
leaning, veering, or rolling. • Bilateral 
involvement causes wide head excursions, 
truncal ataxia; ± deafness. • Vomiting and 
nausea may occur during the acute phase. 
• Saliva and food dropping from corner of 
the mouth; inability to blink; ocular discharge. 
• Anisocoria (smaller pupil on affected side), 
protrusion of the third eyelid, enophthalmos 
and ptosis (Horner’s syndrome) may be noted.Physical Examination Findings
• The presence of aural erythema, discharge, 
and thickened and stenotic external canals 
support otitis externa. • Pain upon opening 
of the mouth or on bulla palpation. • Gray, 
dull, opaque, and bulging tympanic 
membrane on otoscopic examination 
indicates middle ear exudate. • Dental 
tartar, gingivitis, tonsillitis, or pharyngitis 
may be present and have a role in the 
pathogenesis. • With severe infections, the 
ipsilateral mandibular lymph nodes may be 
enlarged. • Corneal ulcer from inability to 
blink or KCS.
• Unilateral damage to vestibular portion of 
cranial nerve VIII—ipsilateral head tilt, 
leaning, veering, falling, or rolling. 
• Nystagmus—resting or positional; rotary or 
horizontal; fast phase characteristically 
opposite the affected side, and does not 
change in direction with a change in head 
position. • Vestibular strabismus—ipsilateral 
ventral deviation of eyeball with neck 
extension. • Bilateral damage of vestibular 
portion of cranial nerve VIII—patient 
reluctant to move, may stay in a crouched 
posture, wide head excursions; physiologic 
nystagmus poor to absent. • Facial nerve 
damage—ipsilateral paresis/paralysis of the 
ear, eyelids, lips, and nares; reduced tear 
production (indicated by Schirmer tear test). 
• Chronic facial paralysis—contracture of the 
affected face caused by fibrosis of denervated 
muscles. • Sympathetic nerve damage—
ipsilateral Horner’s syndrome; always miosis; 
may also note protrusion of third eyelid, 
ptosis, and enophthalmos.
CAUSES
• Bacteria— Staphylococcus  spp., Streptococcus  
spp., Proteus  spp., Pseudomonas  spp., 
Pasteurella  spp., and E. coli  and obligate 
anaerobes. • Fungi—yeast ( Malassezia  spp., 
Candida  spp.) and Aspergillus . • Ear mites 
predispose to secondary bacterial infections. 
• Foreign bodies (e.g., grass awns, foxtail 
awns, or spear grass in endemic areas), 
trauma, polyps, tumors (e.g., fibromas, 
squamous cell carcinoma, ceruminous gland 
carcinoma, primary bone tumors). 
• Iatrogenic damage during cleaning or 
flushing or in investigation of otitis externa.
• Recurrent otitis externa. • Nasopharyngeal 
polyps and inner, middle, or outer ear 
neoplasia may predispose to bacterial 
infection. • Ear-cleaning solutions (e.g., 
chlorhexidine) may be irritating to middle/
inner ear or be ototoxic. These should be 
avoided if tympanum is ruptured.  DIAGNOSIS
• Congenital vestibular anomalies—signs 
present from birth. • Hypothyroidism may be 
associated with cranial nerve VII and VIII 
deficits. Abnormal thyroid profile supports 
diagnosis. • Neoplasia and nasopharyngeal 
polyps are common causes of refractory and 
relapsing otitis media and interna. Diagnosed by 
oral and otic exam and imaging of the head. 
• Idiopathic vestibular disease (old dogs and 
young to middle-aged cats), idiopathic facial 
paralysis, and idiopathic Horner’s syndrome are 
diagnoses made by exclusion. • Cryptococcus  is 
reported to be associated with peripheral 
vestibular disease in cats. • T raumatic causes may 
have physical external evidence of injury, and 
history supporting occurrence of a traumatic 
event. • Thiamine deficiency occurs in cats with 
a history of an all-fish diet or persistent anorexia; 
causes bilateral central vestibular signs. 
• Metronidazole used for an extended duration 
and/or at a high dose damages the vestibular 
portion of the cerebellum. Signs of bilateral 
cerebellar disease and history of metronidazole 
use. • Central vestibular disease may cause 
lethargy, somnolence, vertical nystagmus, and 
other brainstem signs.
• Leukocytosis with left-shift may be noted. 
• Globulins may be high if chronic infection.
• Blood, urine cultures may show growth if 
hematogenous source of infection. • Low 
thyroxine (T4), free T4 with normal or high 
thyroid-stimulating hormone (TSH) level 
with hypothyroidism.
IMAGING
• Video-otoscopy—enables detailed 
examination of external ear canal and 
tympanic membrane. With middle ear 
exudate, the membrane may appear cloudy. 
Helpful in evaluating the integrity of the 
tympanic membrane, obtaining samples for 
cytology and culture/sensitivity, and performing 
therapeutic lavages of the ear canal and middle 
ear cavity. • Bullae radiographs—not sensitive. 
May show thickening of the bullae and 
petrous temporal bone with chronic disease, 
boney lysis with severe cases of osteomyelitis, 
evidence of neoplasia, or may be normal. 
• CT or MRI—necessary to demonstrate 
fluid and soft tissue density within the middle 
ear and extent of involvement of adjacent 
structures. CT is better at revealing associated 
bony changes, MRI for evaluating soft tissue 
structures including brainstem and cerebellum.

1016  Blackwell’s Five-Minute Veterinary Consult  
ODIAGNOSTIC PROCEDURES
• Myringotomy—insert a spinal needle 
(20-gauge; 2.5- to 3.5-inches) through the 
otoscope and tympanic membrane to aspirate 
middle ear fluid for cytologic examination 
and culture and sensitivity. Examine for 
bacterial and fungal causes of infection. 
(BAER)—tests the peripheral and central 
auditory pathways, detects hearing loss. 
• CSF analysis—if evidence of intracranial 
extension, perform culture and sensitivity.
Purulent exudate within the middle ear cavity 
surrounded by a thickened bullae and 
microscopic evidence of degenerate neutro -
phils with intracellular bacteria or other 
microorganisms; other causes such as polyps 
  TREATMENT
• Inpatient care is recommended with severe 
debilitating infection or if significantly 
compromising neurologic signs are present. 
• Outpatient care is appropriate if the patient is 
stable, pending further diagnostics, if indicated.
DIET
• If vomiting, withhold food and water for 
12–24 hours. • If unable to stand or severely 
disoriented, hand-feed and water small 
amounts frequently. Ensure that the patient is 
sternal during feeding to decrease risk of 
• Inform client that most bacterial infections 
resolve without recurrence when treated early 
with an aggressive course of long-term, broad- 
spectrum antibiotics. • Warn client that 
relapsing signs may occur, that the patient 
may improve but may never be neurologically 
normal. • Warn client that the condition may 
require surgical intervention.
• Severity of neurologic signs is not directly 
related to degree of pathology, and should not 
be used to make decisions regarding need for 
surgical intervention. • Surgical treatment is 
indicated for patients with evidence of middle 
ear exudate, osteomyelitis refractory to 
medical management, nasopharyngeal polyps, 
or neoplasia. • Bullae osteotomy allows 
drainage of the middle ear cavity. • Total 
ablation of ear canal is indicated when otitis 
media is associated with recurrent otitis 
externa or neoplasia. • Perform cytologic 
examination and culture of middle ear effusion and histopathology of abnormal 
tissue sampled at the time of surgery.
• Topical sterile water, saline, or T rizEDTA-
based otic antimicrobial preparations if 
tympanum is ruptured. • T reat mites if 
present. • Long-term (6–8 weeks) topical and 
systemic antibiotics selected on basis of 
culture and sensitivity, if available. 
• Amoxicillin/clavulanic acid (12.5–22 mg/
kg q12h PO) is a good first-choice antibiotic. 
• Fluoroquinolone or third-generation 
cephalosporins are good second alternatives or 
can be used in combination, if culture and 
sensitivity unavailable; enrofloxacin (Baytril) 
5–10 mg/kg q24h (dogs), 5 mg/kg q24h 
(cats), or marbofloxacin (Zeniquin 5 mg/kg 
q24h), or cefpodoxime (Simplicef 10 mg/kg 
q12h); clindamycin (Cleocin 5–30 mg/kg 
q12h), if anaerobes are suspected. • In cats, 
where oral dosing is too challenging, consider 
using cefovecin (Convenia) 8 mg/kg SC every 
2 weeks. This can also be used in combination 
with a fluoroquinolone. • Antiemetics to 
treat or prevent nausea, vomiting, and 
dizziness. Meclizine (Antivert, Antrizine, 
Bonine, Dramamine Less Drowsy Formula) 
12.5 mg PO q24h (dogs <10 kg and cats), 
25 mg PO q24h (dogs >10 kg); or maropitant 
citrate (Cerenia) 1 mg/kg SC or 2 mg/kg PO 
q24h (dogs), 1 mg/kg SC or 1 mg/kg PO 
q24h (cats); or dolasetron mesylate (Anzemet) 
0.6 mg/kg IV q24h (dogs, cats).
• If ruptured tympanum or associated 
neurologic deficits, avoid oil-based or 
irritating external ear preparations (e.g., 
chlorhexidine) and aminoglycosides, which 
are toxic to inner ear structures. • Use topical 
and systemic corticosteroids judiciously in 
treatment of otitis media or interna. May 
exacerbate infection. Reserve for cases in 
which flushing of the ear canal is prevented 
by inflammation, or to treat edema associated 
with intracranial spread of infection.
Avoid vigorous external ear flush.
  FOLLOW-UP
Evaluate for resolution of signs after 10–14 
days or sooner if the patient is deteriorating.POSSIBLE COMPLICATIONS
• Signs associated with vestibular (head tilt) 
and facial nerve damage or Horner’s syndrome 
may not resolve. • Severe middle/inner ear 
infections may spread to brainstem or 
sometimes forebrain. Clinical signs indicate 
central vestibular lesion, typically preceded by 
peripheral vestibular or middle/inner ear signs. 
Aggressive surgical debridement and antibiotic 
therapy are required. • Osteomyelitis of the 
petrous temporal bone and middle ear effusion 
are common sequelae to severe, chronic otitis 
externa. • Complications following bulla 
osteotomy include Horner’s syndrome, facial 
paralysis, onset or exacerbation of vestibular 
dysfunction, and deafness.
• Otitis media-interna is usually responsive to 
medical management. To decrease likelihood 
of relapse, a 2- to 4-month course of antibiotic 
is recommended. • When medical management 
of otitis externa is ineffective, consider lateral 
ear resection. • Vestibular signs typically 
improve in 2–6 weeks.
Ear mites more common in kittens and 
puppies.
SEE ALSO
• Facial Nerve Paresis and Paralysis.
• Otitis Externa and Media.
• BAER = brainstem auditory evoked response. 
• T4 = thyroxine.
• TSH = thyroid-stimulating hormone.
Negrin A, Cherubini GB, Lamb C, et al. 
Clinical signs, magnetic resonance imaging 
findings and outcome in 77 cats with 
vestibular disease: a retrospective study. J 
Feline Med Surg 2010, 12:291–299.
Sturges BK, Dickinson PJ, Kortz GD, et al. 
features, and outcome after surgical and 
medical treatment of otogenic intracranial 
infection in 11 cats and 4 dogs. J Vet Intern 
Med 2006, 20:648–656.
Buglione
available onlineOtitis Media and Interna  (continued)

Canine and Feline, Seventh Edition  1017
O
Ovarian Remnant Syndrome
  BASICS
OVERVIEW
• Ovarian remnant syndrome is the presence 
of behavioral and/or physical signs of estrus 
in a female dog or cat reported as having 
previously undergone ovariohysterectomy or 
ovariectomy (OVH/OE).
• It is caused by the presence of functional 
residual ovarian tissue.
• It is responsible for 17% of all post-OVH/
OE complications.
• Female dog and cat; more common in 
the cat.
• No breed predisposition or geographic 
• Signs of an estrous cycle usually occur 
months to years after OVH/OE; can begin 
within days after surgery.
SIGNS
Bitches
Estrogen Influence
• Attraction of male dogs.
• Swelling of the vulva.
• Mucoid to sanguineous vaginal discharge.
• Flagging.
• May allow copulation.
• Signs of pro-estrus last an average of 9 days; 
signs of estrus last an average of 9 days; 
average interval between signs of estrous 
cycles is 7 months.
• Signs are typically cyclical (i.e., q6 months), 
unlike estrogen toxicity.
Progesterone Influence
• Prominent vulva compared to patients with 
complete OVH/OE.
• Enlargement of the uterine stump ultra  - 
sonographically.
• Uterine stump pyometra can develop due 
to progesterone effect.
Queens
• Restlessness.
• Head rubbing.
• Rolling.
• Tail deviation and treading the hind limbs.
• Demonstrate typical behavioral signs of estrus 
in a cyclical (seasonally polyestrous) fashion.
• Estrus lasts 2–19 days, followed by an 
interestrous interval that lasts for 8–10 days 
unless ovulation and luteinization occurred, 
in which case the interestrous interval is at 
least 45 days.
• Enlargement of the uterine stump 
ultrasonographically.• Uterine stump pyometra can develop due 
• Failure to remove both ovaries completely.
• No correlation with age at OVH/OE, 
difficulty of surgery, obesity of patient, or 
experience of surgeon.
• Presence of anatomically abnormal ovarian 
tissue (fragmentation into the broad 
ligament) is possible; more common in 
queens.
• Supernumerary ovary (rare).
• Experimentally, functionality returns to 
ovarian tissue removed from its vascular 
supply and replaced into or onto the lateral 
abdominal wall, mesentery, or serosal surface.
  DIAGNOSIS
• Inflammation or infection of the 
genitourinary tract.
• Vaginal hemorrhage due to trauma, foreign 
body, or coagulopathy.
• Uterine stump granuloma secondary to 
local pathology (foreign body reaction to 
suture material or grass awn).
• Neoplasia of a remnant portion of the 
tubular tract (uterine stump leiomyoma or 
leiomyosarcoma).
• Neoplasia of an ovarian remnant (granulosa 
cell tumor, carcinoma, luteoma, functional 
teratoma), typically not cyclical.
• Neoplasia of the urinary tract (transitional 
• Vascular anomalies of the genitourinary 
tract.
• Exogenous estrogen administration, 
typically not cyclical.
• Exposure to human transdermal hormone 
replacement therapy, typically not cyclical.
• Endogenous extra-ovarian source of 
estrogen—adrenal pathology (rare), typically 
not cyclical.
• Chronic blood loss anemia if vaginal 
hemorrhage is profound.
• Pancytopenia from estrogen toxicity is 
uncommon.
• An inflammatory leukogram and 
isosthenuria can occur subsequent to uterine 
stump pyometra.
 OTHER LABORATORY TESTS
• Observation of behavioral and physical 
signs of estrus together with vaginal cytology 
and/or measurement of serum progesterone 
concentration confirming the presence of 
functional ovarian tissue.
• Vaginal cytology—vaginal mucosal 
cornification is an excellent bioassay for elevated plasma estradiol concentrations (see 
Breeding, Timing).
◦ Bitch—epithelial cell cornification is 
generally >90% during estrus (superficial 
and pyknotic or anuclear cells).
◦ Queen—epithelial cell cornification ranges 
from 10% to 40% (usually retain nucleus); 
clearing (absence of debris and clumping of 
cells) occurs in 90% of smears during estrus.
• Serum progesterone:
◦ Bitch—a serum progesterone concentration 
>2 ng/mL (measured 1–3 weeks after 
behavioral estrus) is consistent with functional 
luteal tissue. Gonadotropin-releasing 
hormone (GnRH, 50  μg, IM), human 
chorionic gonadotropin (hCG; 400 IU, IV, or 
500 IU, IV and 500 IU, IM) can be used to 
attempt to induce ovulation/luteinization for 
diagnostic purposes; serum progesterone 
concentration is measured 2–3 weeks later. 
Note: both normal and pathologic ovarian 
tissue may fail to respond to either hormone.
◦ Queen—ovulation and luteinization is 
stimulated most commonly by coital 
stimulation during behavioral estrus, and 
serum progesterone concentration is measured 
2–3 weeks later; post-stimulation serum 
progesterone concentrations >2 ng/mL are 
consistent with adequate coital stimulation 
and functional luteal tissue. Feline ovulation 
can occur spontaneously. GnRH (25  μg, IM) 
can be used to attempt to induce ovulation or 
luteinization for diagnostic purposes; serum 
progesterone concentration is measured 2–3 
weeks later. Both normal and pathologic 
ovarian tissue may fail to respond.
• Luteinizing hormone (LH) assay (Witness 
LH, Zoetis)—should be positive (>1 ng/mL) 
in a completely gonadectomized bitch due to 
lack of pituitary feedback. When an 
unexpected positive result is obtained in a 
bitch suspected to have a remnant, consider 
repeating in >24 hours to rule out inadvertent 
detection of the LH surge in the estrual bitch 
(should also have representative vaginal 
cytology with superficial cells predominating). 
If both are positive, then the bitch has been 
spayed. A negative test (<1 ng/mL) is found 
in intact dogs unless performed at the 
moment of the natural LH surge. The assay is 
licensed for use in the bitch, but likely is 
applicable in male dogs, toms and queens, 
provided that the queen is exposed to >14 
hours of light/day. Note: exogenous estrogen 
exposure in a gonadectomized dog can cause 
the LH to become misleadingly negative.
• Anti-Müllerian hormone (AMH) testing: A 
positive test in a bitch or queen >6 months of 
age supports the presence of ovarian tissue (UC 
Davis Clinical Endocrinology Laboratory, 
Animal Health Diagnostic Center, Cornell 
University). In cases with a negative AMH but 
convincing clinical evidence supporting 
remnant syndrome, investigators advise 
obtaining a progesterone to identify persistent

1018  Blackwell’s Five-Minute Veterinary Consult  
Oluteal structures lacking AMH. AMH 
differentiates exogenous estrogen exposure 
(negative) from the ovarian remnant (positive).
• Cytology of vulvar discharge can be 
suppurative if a uterine stump granuloma or 
pyometra exists.
• Provocative adrenal testing (pre- and post-
adrenocorticotropin [ACTH] administration).
IMAGING
• Can be used to support a diagnosis of 
ovarian remnant syndrome that is based on 
cytology and hormonal profiles; guides the 
surgical approach.
• Remnant ovarian tissue is most visible 
during the follicular phase (anechoic, cystic 
structures) or the luteal phase (hypo- or 
isoechoic cystic structures).
• Ultrasonographic imaging of ectopic 
ovarian tissue requires technical expertise and 
is best accomplished with a higher frequency, 
linear transducer (8–10 mHz). Ovarian 
remnants containing follicular or luteal 
structures often cause distal enhancement due 
to their fluid content; this can be used to 
locate them caudolateral to the ipsilateral 
kidney (see Web Figure 1).
• Evaluate the region dorsal to the bladder for 
a uterine remnant, which can enlarge under 
hormonal influence or with pathology (see 
Web Figure 2a,b).
• Evaluate the adrenal glands for normal size 
and shape. Normal canine adrenal glands are 
<0.51–0.74 cm in sagittal (see Web Figures 3 
and 4).
• Exploratory laparotomy/laparoscopy—
removal of residual ovarian tissue confirms 
and resolves the problem.
• Identification of residual ovarian tissue is 
facilitated by the presence of follicles or corpora 
lutea; schedule procedure during times of elevated 
progesterone or during behavioral estrus.
• Histopathology—always submit visible 
ovarian tissue; if no visible ovarian tissue is 
identified, submit all residual tissue at the ovarian pedicles. This helps confirm the 
diagnosis and screens for malignancy. Submit 
revised abnormal uterine stump tissue for 
aerobic and anaerobic cultures and histo -
pathology (hormone influence, inflammatory 
response, malignancy).
  TREATMENT
• Surgical removal of residual ovarian tissue.
• Surgical removal of diseased uterine stump 
• Although not curative, restricting light 
exposure to <8 hours per day can suppress 
signs of estrus in some, but not all, cats with 
• Progestational or androgenic compounds to 
suppress follicular ovarian activity—not 
recommended because of undesirable side 
effects (mammary neoplasia, diabetes, 
undesirable behavior, hepatopathy, derma  - 
topathy).
• GnRH agonist (Suprelorin) administration 
will offer a viable alternative or adjunctive 
therapy to laparotomy when perfected and 
commercially available in the United States.
  FOLLOW-UP
• Removal of functional luteal tissue may 
induce transient signs of pseudopregnancy in 
dogs and cats postoperatively (see False 
Pregnancy).
• The use of oral antiprolactin agents 
(cabergoline) can be considered for 
pseudopregnancy.EXPECTED COURSE AND PROGNOSIS
• Successful removal of remnant ovarian 
tissue should result in cessation of clinical 
signs of estrus/diestrus.
• Adjunctive therapy for stump pyometra 
(systemic antibiotics, supportive care) as 
• Adjunctive therapy for functional ovarian 
neoplasia as indicated.
SEE ALSO
• False Pregnancy.
• Hyperestrogenism (Estrogen Toxicity).
• ACTH = adrenocorticotropic hormone.
• AMH = anti-Müllerian hormone.
• GnRH = gonadotropin-releasing hormone.
• hCG = human chorionic gonadotropin.
• LH = luteinizing hormone.
• OE = ovariectomy.
• OVH = ovariohysterectomy.
Davidson AP , Feldman EC. Ovarian and 
estrous cycle abnormalities. In: Ettinger SJ, 
Elsevier, 2005, pp. 1649–1655.
Miller DM. Ovarian remnant syndrome in 
dogs and cats: 46 cases (1988–1992). J Vet 
Diagn Invest 1995, 7:572–574.
Place NJ, Hansen JL, Chereskin SE, et al. 
Measurement of serum anti-mullerian 
hormone concentration in female dogs and 
cats before and after ovariohysterectomy. 
J Vet Diagn Invest 2011, 23:524.
Authors  Autumn P . Davidson and Tomas 
W. Baker
Consulting Editor  Erin E. RuncanOvarian Remnant Syndrome  (continued)

Canine and Feline, Seventh Edition  1019
O
Ovarian Tumors
  BASICS
OVERVIEW
• Epithelial (carcinoma), germ cell 
(dysgerminoma and teratoma), and sex cord 
stromal (granulosa cell tumor, Sertoli–Leydig 
cell tumor, thecoma, and luteoma) tumors.
• Dogs—rare (0.5–1.2% of tumors); 40% 
carcinomas, 10% germ cell, and 50% sex cord.
• Cats—rare (0.7–3.6% of tumors); 15% 
germ cell, and 85% sex cord.
• Metastasis common for malignant epithelial 
and germ cell tumors in the dog and all 
tumors in cats.
• Some tumors produce hormones resulting 
in paraneoplastic syndromes.
• Middle-aged to older animals.
• Teratoma may develop in young patients.
SIGNS
• Bilaterally symmetrical alopecia; pancyto -
penia; masculinization (hormone-secreting 
tumors with associated paraneoplastic 
manifestation).
• Malignant ascites or pleural.
• Effusion (carcinomatosis)—occasionally.
• Other signs associated with mass effects of 
the tumor (abdominal discomfort, compression 
of adjacent organs).
• Intact sexual status.
• Dogs—pointer, English bulldog, boxer, 
German shepherd dog, and Yorkshire terrier 
at risk.
 DIAGNOSIS
• Other causes of abdominal effusion 
including vasculitis and pancreatitis.
• Other mid-abdominal masses or 
gossypiboma (foreign body granuloma).
• Ovarian cysts, paraovarian cysts, cystic rete 
tubules, vascular hematomas, metastatic 
• No consistent abnormalities.
• Pancytopenia in dogs with functional 
estrogen-secreting tumors.
Serum progesterone—levels >2 mg/mL with 
functional tumors.
IMAGING
unilateral or bilateral mid-abdominal mass at 
the caudal pole of the kidney or effusion, 
mineralization of tumor may be seen.• Abdominal ultrasonography—confirm 
abdominal radiographic findings and 
provide greater certainty for the origin of 
mass effect.
• Advanced imaging—CT or MRI can 
provide detailed assessment for origin and 
associated tissues that might be involved in 
disease process.
• Thoracic radiography—may reveal distant 
metastasis (rare).
• Cytologic evaluation of pleural or 
abdominal fluid—may be diagnostic for 
malignant effusion (carcinomatosis).
• Cytologic evaluation of tumor—tumor cells 
may readily implant on the body wall via 
fine-needle aspirate. Therefore, excisional 
biopsy is often recommended over fine-needle 
aspirate of the mass.
• Histopathologic examination—necessary 
for definitive diagnosis.
  TREATMENT
for a solitary mass.
• Peritoneal transplantation during surgical 
removal is possible; change gloves and surgical 
instruments during procedure.
• Laparoscopic-assisted ovariohysterectomy 
may be possible for smaller tumors.
• Chemotherapy—little information for dogs 
and cats, no standard therapy.
• Cisplatin—successful treatment reported in 
three dogs and treatment of choice for 
comparative tumors in human beings.
• Cisplatin—do not use in dogs with renal 
disease; do not use without appropriate and 
concurrent diuresis; do not use in cats (fatal).
• Chemotherapy may be toxic; seek advice if 
unfamiliar with these agents.
  FOLLOW-UP
• Abdominal ultrasonography and thoracic 
radiography—every 3 months; monitor for 
recurrence and metastasis.
• Ovariohysterectomy—prevention.
• Chemotherapy—has potential to lengthen 
survival.  MISCELLANEOUS
• Ovarian cysts.
• Ovarian remnant syndrome.
Morrison WB. Cancer of the reproductive 
Dogs and Cats: Medical and Surgical 
Management. Jackson, WY: Teton 
Patnaik AK, Greenlee PG. Canine ovarian 
neoplasms: a clinicopathologic study of 
71cases including histology of 12 granulosa 
cell tumors. Vet Pathol 1987, 24:509–514.
Author  Heather M. Wilson-Robles
Terrance A. Hamilton.

1020  Blackwell’s Five-Minute Veterinary Consult  
OOvulatory Failure
  BASICS
OVERVIEW
• Breakdown in the process of ovulation, 
without normal corpus luteum formation and 
progesterone production.
• Clinical signs of prolonged estrogen 
production; may develop estrogen toxicity.
• Intact bitch or queen of any age—greater 
predisposition in older females.
• Reported in 1.2% of bitches presented for 
breeding management.
• No breed predisposition for anovulation; 
follicular cysts reported more commonly in 
German shepherd dog, Malamute, golden 
retriever, bouvier des Flandres, and Labrador 
• Heritability unknown.
SIGNS
• Prolonged proestrus or estrus.
• Edematous vulva.
• Sanguineous vulvar discharge (bitch).
• Anestrus.
• Decreased interestrous interval.
• Bilaterally symmetric alopecia (progressive, 
nonpruritic).
• If neoplasia—abdominal mass ± ascites.
• If chromosome abnormality—genitalia 
ranges from infantile or ambiguous to normal 
to enlarged clitoris or os clitoris; small stature; 
anestrus.
• Failure of release of gonadotropin-releasing 
hormone (GnRH) or luteinizing hormone (LH).
• Failure of receptors on the follicular wall to 
respond to LH.
• Failure of the follicles to produce adequate 
estrogen to elicit GnRH surge.
• Functional follicular cysts—may mimic 
normal estrous cycle initially, but estrus 
persists and ovulation does not occur.
• Immune-mediated oophoritis.
• Cachexia or obesity.
• Stress (performance, travel, kennel).
• Adrenal disease.
  DIAGNOSIS
• Prolonged proestrus (up to 30 days) or 
estrus (up to 30 days).
• Split heat—anovulatory cycle will be 
followed by a normal, fertile, ovulatory cycle 
in 1–8 weeks.
• Hypoluteoidism.
• Granulosa cell tumor or serous 
cystadenoma—abdominal mass; enlarged 
ovary on ultrasound; ± ascites; ± bilaterally-
symmetric alopecia.• Ovarian senescence.
• Chromosomal abnormality—may develop 
follicles that either ovulate or regress.
• Exogenous estrogen administration or 
exposure.
If estrogen toxicity—normocytic, normochro -
mic anemia, thrombocytopenia, leukocytosis 
followed by leukopenia.
• Serum progesterone concentration <4–10 ng/
mL over multiple samplings once vaginal 
cytology exceeds 70% anucleated superficial 
cells. Often remains 3–5 ng/mL for prolonged 
period, never exceeding 10 ng/mL. Vaginal 
cytology eventually returns to proestrus/anestrus 
characteristics, confirming ovulatory failure.
• Karyotyping—diagnose chromosomal 
IMAGING
• Radiography—ovarian mass.
• Ultrasonography—multiple anechoic 
structures on the ovary may be considered 
follicles, anechoic structures >1 cm 
considered cystic; enlarged ovaries may be 
neoplastic; anechoic structures with thickened 
walls may indicate luteinization (partial or 
complete) of follicular structures. Daily 
ultrasonography to document ovulation; 
color Doppler can assess ovarian follicular 
blood flow (increased with follicles, minimal 
with luteal structures).
Exploratory laparotomy to examine the 
ovaries or to obtain ovarian biopsies—the 
ovarian bursa must be opened to visualize 
the ovary.
  TREATMENT
N/A
• Ovulation induction may be attempted 
once cytology reaches >70% anucleated cells 
and follicles are >4–5 mm (toy to small-breed 
canine), 5–7 mm (medium to large-breed 
canine), 7–10 mm (giant-breed canine), or 
2–3 mm (feline).
• Ovulation-inducing agents:
◦ GnRH: 1.1–2.2  μg/kg IM or IV; 25  μg/
cat IM; may repeat daily for 1–3 days in 
bitches, single dose for queens.
◦ Human chorionic gonadotropin (hCG): 
500–1,000 IU/dog IM; 500 IU/queen IM; 
may repeat in 2–3 days if ovulation does 
not occur.◦ GnRH and hCG may be given 
concurrently or alternating days.
◦ Deslorelin implant (2.1 mg implant—
Ovuplant® or 4.7 mg implant—Suprelorin®) 
placed subcutaneously. If breeding and 
ovulation is confirmed (progesterone 
>10 ng/mL), implant should be removed. If 
not breeding, leave implant in place.
◦ In queens, cervical stimulation may be 
performed from initial induction several 
times daily for 24–48 hours.
  FOLLOW-UP
• Monitor progesterone concentrations 
during pregnancy—luteal failure or 
hypoluteoidism more common with induced 
• Monitor progesterone after induction to 
confirm normal rise.
• Serial ultrasound exams (using color Doppler) 
may be useful to document ovulation.
Bilaterally symmetric nonpruritic alopecia 
(with prolonged estrus).
• Anovulation may be hereditary; discuss 
with owner prior to breeding.
• Subsequent cycles may be normal, necessi -
tating no treatment, or abnormal again. 
SEE ALSO
Meyers-Wallen VN. Unusual and abnormal 
canine estrous cycles. Theriogenology 2007, 

Canine and Feline, Seventh Edition  1021
P
Pain (Acute, Chronic, and Postoperative)
  BASICS
• Unpleasant sensory or emotional experience 
associated with actual or potential tissue 
damage (adaptive pain) or altered sensory 
neurobiology (chronic pain).
• The inability for the animal to communi­
cate does not negate presence of pain and the 
need for appropriate pain ­relieving treatment.
• With physiologic pain, an application of a 
noxious stimulus activates specialized nerve 
endings called nociceptors; nociceptors 
transduce noxious chemical, mechanical, or 
thermal stimuli into electrochemical 
potentials that are transmitted via sensory 
nerves from the affected tissue to the spinal 
cord.
• In the dorsal horn of the spinal cord, the 
incoming first ­order peripheral nerve synapses 
with ascending spinal neurons, which 
terminate in the brainstem. Incoming noxious 
information can be modulated in the dorsal 
horn by other incoming information, 
descending inhibitory nerve impulses, or 
pharmacologic inhibition by several classes of 
drugs. The ascending neurons synapse in the 
brainstem to form ascending tracts that end 
in the cortex, where sensation occurs. 
Neuroendocrine and physiologic responses 
(e.g., tachycardia, elevated cortisol) to 
noxious stimuli may originate from the 
brainstem and do not necessarily correlate 
with the perceived intensity of pain.
• Nociceptive processes (i.e., transduction, 
transmission, and modulation) appear to be 
similar anatomically and physiologically in 
most mammalian and many non ­mammalian 
species. The perception of pain may vary 
between species and individuals of the same 
species since anatomic differences in cortical 
development exist and integration of past 
experiences and learned behaviors varies.
• Prolonged activity in nociceptive pathways 
(e.g., days, weeks, or months) from chronic 
injury or disease, or injury to nervous system 
tissues, may cause altered neuroprocessing 
resulting in sensitization of these pathways 
and hyperresponsiveness. This may cause an 
increased response to a stimulus not normally 
considered noxious (allodynia).
• Pain may originate from any tissue, 
including the nervous system itself. In 
humans, certain pain syndromes may be 
associated with fear, anxiety, or depression in 
the absence of any observable injury.
• The physiologic response to pain can 
include decreased immune function, 
increased catabolism, and elevated neuro­endocrine markers of stress. Pain can result in 
a loss of function of affected tissues.
GENETICS
Age, sex, breeding strain, and species can 
influence responses to noxious stimuli. Genes 
have been described that modify individual 
behavioral responses to noxious stimuli in several 
species. Genes may also be variably expressed 
depending on stimulus intensity and duration, 
which can lead to altered neuroprocessing and 
maladaptive or chronic pain.
• Evolutionarily, aversion to noxious stimuli 
was protective to organisms, keeping them 
away from harm.
• While acute pain is beneficial to warn or 
teach an animal about potential harmful 
objects in its environment, persistent acute 
pain associated with surgery or injury does 
not benefit the patient and should be treated 
• Any form of chronic pain syndrome does 
not serve a protective function and should be 
treated.
SIGNS
• Behavioral signs of pain and distress vary 
considerably among individuals.
• Experience, environment, age, species, and 
other factors can modify the intensity of the 
reaction to noxious stimuli or to an altered 
neurobiology associated with maladaptive or 
chronic pain.
• The most obvious clinical signs of distress 
in the dog and cat can include vocalization, 
agitation, abnormal posture or gait, thrashing, 
hyperesthesia, or hyperalgesia.
• More subtle signs shared by many 
conditions include trembling, lethargy, 
reduced appetite, stupor, and biting.
• Tachypnea, tachycardia, mydriasis, and 
hypertension are signs observed with the 
stress response that may also accompany pain; 
these are nonspecific and present in many 
nonpainful conditions. The stress response is 
often not associated with chronic pain due to 
adaptation.
• Clinical signs associated with chronically 
painful conditions may be very subtle or 
difficult to evaluate since homeostatic 
mechanisms tend to help the animal 
compensate. Chronically painful conditions 
are often associated with decreased activity, 
lameness, and/or depression.
CAUSES
• Physiologic or adaptive pain can be caused 
by perceived or actual tissue disruption 
associated with trauma or surgery and also by 
chronic degenerative changes and inflammation 
associated with conditions such as osteoarthritis.
• Pain that extends beyond the initial tissue 
damage and healing processes is pathologic 
(maladaptive) and may indicate that the initiation of altered nervous system processing 
• All animals that experience surgical or 
traumatic tissue damage or have recently 
altered behavior should be evaluated for the 
presence of pain.
• Due to the increasing prevalence of 
degenerative diseases in older patients, 
routine examination should include 
evaluation for pain.
• Pain intensity may not always correlate with 
the degree of tissue damage. However, more 
invasive soft tissue and orthopedic procedures 
or inflammatory disease progression in older 
patients are likely associated with greater pain.
  DIAGNOSIS
• Identifying pain in veterinary patients is a 
diagnosis, and the medical record should 
reflect the veterinarian’s clinical diagnostic 
and treatment plan.
• Acute pain is almost always accompanied 
by tissue damage or disease, and diagnosis 
and treatment of the primary disorder should 
be done before or concomitantly with 
treatment of pain. The presence or absence 
of pain is sometimes used as a way of 
monitoring and diagnosing some conditions, 
and treatment should be in accordance with 
good medical practice. Pain should be 
differentiated from distress associated with 
other factors, such as restraint, restrictive 
bandaging, and separation from owners. 
Drugs used to treat pain, particularly opioids 
and dissociative anesthetics, may cause 
dysphoria, which often resembles and can be 
confused with signs of pain and distress.
• Cortisol release associated with acute pain 
may appear as a stress leukogram.
• Hyperglycemia may also be observed in 
some patients, but can also be seen with 
anesthesia in the absence of tissue trauma.
• Normal laboratory test values do not rule 
out the presence of pain.
N/A
IMAGING
• Many painful patients have underlying 
changes in anatomic structures observable on 
ultrasound, radiography, CT or MRI.
• Chronic pathologic tissue changes such as the 
degree of osteophyte formation with osteoarthritis 
do not necessarily always correlate with the degree 
of pain and dysfunction experienced by the 
patient. Some patients can be painful without 
observable tissue or structural changes.

1022  Blackwell’s Five-Minute Veterinary Consult  
PDIAGNOSTIC PROCEDURES
• Review patient signalment, obtain a 
thorough history, and include pain assessment 
as part of every physical examination. The 
pain score should be recorded in the patient’s 
record along with temperature, pulse, and 
respiration.
• Thoroughly evaluate underlying conditions 
that may be contributing to pain and treat 
• Use a species ­specific scoring tool for pain 
assessment to decrease subjectivity and 
observer bias. This will result in more effective 
pain management. Such tools are referred to 
as multifactorial clinical measurement 
instruments (CMIs) and are available for acute 
postoperative or chronic pain.
• CMIs for acute postoperative pain involve 
observing the patient without interaction; 
observing the patient while interacting with a 
caregiver; observing the patient’s response to 
palpation of the surgical site; and assigning a 
numerical score using a dynamic interactive 
visual analogue scale. The reevaluation interval 
will depend on the procedure, duration of 
intervention chosen, and previous pain score.
• CMIs for chronic pain primarily involve 
owner observations of their pets regarding 
exercise tolerance and general activity; ability to 
stand, walk, do stairs, jump, or rise; grooming 
behavior; and urination or defecation habits.
• Complete abolishment of pain may not be 
possible or desirable if analgesic administration 
results in excessive adverse effects. Therapy 
should aim to make pain tolerable.
  TREATMENT
• Analgesic drug selection depends on 
species, pain intensity, and underlying cause.
• T reat the underlying cause at the same time 
• Acupuncture, prescribed activity (e.g., 
physical therapy), mesenchymal stromal cell 
or platelet ­rich plasma injection, and physical 
manipulation (massage, trigger point 
manipulation, chiropractic) may be useful 
adjunctive treatment modalities for certain 
types of painful musculoskeletal conditions.
• If the patient’s quality of life is not 
acceptable after all reasonable therapeutic 
options have been explored, euthanasia may 
be the most humane option.
• General good nursing practices.
• Nonpharmacologic, including bandaging 
and hydrotherapy, may be appropriate.
ACTIVITY
• Rehabilitation medicine and weight loss is a 
useful adjunct for some musculoskeletal 
conditions.• Cage rest or limited activity may be useful 
for certain types of pain.
DIET
• Dietary changes to help treat the underlying 
condition (e.g., weight reduction for hip 
dysplasia) may be beneficial.
• Many supplements have been marketed that 
may have beneficial effects on articular cartilage 
or modify inflammatory disease progression.
• Commercial veterinary diets are marketed 
specifically for animals with mobility issues.
• When pain medication is dispensed, 
educate clients on what to look for with 
effective treatment, as well as adverse effects. 
Use caution when dispensing opioids to 
clients for at ­home administration and ensure 
they understand requirements for safe storage 
and disposal.
• Inform the client that analgesic effectiveness 
varies and several drugs may need to be tried 
before an effective treatment is found. Pain 
management must be individualized because of 
the neurobiologic complexity of pain perception.
• Clients should be asked to participate in 
evaluation of their pet’s pain, especially 
chronic pain. Species ­specific CMIs are 
available and can help document treatment 
effectiveness.
• Surgical treatment of the underlying 
condition causing pain may be the best 
treatment in some circumstances.
• Ablative procedures (neurectomy) to halt 
pain transmission is not always associated 
with positive results and may result in 
worsening of the painful condition. These 
procedures are rarely performed in 
DRUG(S) OF CHOICE (SEE ALSO 
APPENDIX VII)
• Opioids, alone or in combination with other 
classes of drugs, such as sedative/tranquilizers 
or nonsteroidal anti ­inflammatory drugs 
(NSAIDs), are widely used for the manage­
ment of acute postoperative pain.
• Full μ­opioid receptor agonists, such as 
morphine, hydromorphone, and fentanyl, are 
usually effective for moderate to severe pain. 
Partial agonist or agonist–antagonist drugs, 
such as buprenorphine and butorphanol, are 
usually reserved for mild to moderate pain.
• Opioids generally have poor oral bioavail­
ability, and oral doses should be adjusted 
• Full μ­opioid receptor agonists can be used 
safely in cats; however, doses are usually 
reduced relative to dog doses.• An SC injectable formulation of 
buprenorphine has been approved for 
24­hour postoperative pain control in cats.
• Should dysphoria develop after opioid 
administration, tranquilization with an 
α2­agonist or acepromazine may be beneficial.
• NSAIDs are used most commonly for the 
chronic treatment of painful conditions in 
dogs. They can be safe when administered 
chronically, but gastrointestinal (GI), hepatic, 
and renal adverse effects are possible. The best 
strategy appears to be reducing the dose to 
the lowest effective dose in an individual. If 
chronic administration is anticipated serum 
chemistries should be considered to monitor 
for hepatic and renal adverse effects.
• Veterinary ­approved NSAIDs for dogs and 
cats have demonstrated acceptable safety 
profiles; however, there is no strong indication 
that any particular veterinary ­approved 
NSAID is associated with a greater or lesser 
incidence or prevalence of adverse events.
• Long ­term use of low ­dose meloxicam is 
approved in cats in many countries other than 
• Grapiprant is a non ­cyclooxygenase 
(COX) ­inhibiting NSAID that targets 
prostaglandin E2 (EP4 receptors) approved for 
osteoarthritic pain and inflammation in dogs.
• Liposome ­encapsulated bupivacaine is 
approved for peri ­incisional infiltration in 
dogs undergoing cranial cruciate ligament 
surgery and for peripheral nerve block in cats. 
Gradually released local anesthetic can 
provide analgesia for up to 72 hours. Extralabel 
use is also encountered frequently for other 
types of procedures.
• Additional information is available for 
many drugs and should be referred to when 
considering extralabel use. Owners should be 
informed of the risks of analgesic drug 
therapy in their pet before consenting to 
Neuropathic Pain
T reatment of neuropathic pain is a subcategory 
of pathologic pain. It may originate from brain 
or spinal masses, injury (such as with 
intervertebral disc disease), inflammation, or 
the repetitive stimulation of the pain transmission 
system by a chronic injury outside the CNS. 
Classic signs that accompany neuropathic pain 
are allodynia and hyperalgesia. Neuropathic 
pain does not always respond well to 
traditional analgesics, such as NSAIDs and 
opioids, although these drugs are usually tried 
initially (except for NSAIDs when 
neurosurgery is imminent). T ricyclic anti­
depressants, antiepileptic drugs (e.g., 
gabapentin), N­methyl ­d­aspartate (NMDA) 
receptor antagonists, and other alternative 
(complementary) therapies may be effective. 
Most of these treatments consist of extra ­ or 
off­label use of human medications and require

off­label use of human medications and require 
careful client communication and approval.Pain (Acute, Chronic, and Postoperative)  (continued)

Canine and Feline, Seventh Edition  1023
P
• Opioids may be associated with severe 
respiratory depression in human patients, but 
in most dogs and cats cause only minimal 
respiratory depression. In patients with severe 
respiratory compromise or intracranial 
hypertension, opioids may be contraindicated. 
Most μ­opioid receptor agonists can also alter 
GI and urinary tract motility, resulting in 
constipation, urinary retention, and vomiting.
• NSAIDs can cause GI ulceration, hepato­
pathies, and impaired renal function. 
Preexisting GI, hepatic, or renal disease may 
be a contraindication to their use. Concomitant 
glucocorticoid therapy, severe stress, or 
anorexia may predispose many animals to 
adverse effects. NSAIDs that significantly 
inhibit COX ­1 may also alter platelet 
function and may result in increased surgical 
blood loss. Acetaminophen or acetaminophen ­
containing analgesics should not be used in cats.
• Carefully monitor patients for adverse 
effects and clinical effectiveness following 
administration of analgesic drugs.
• Opioid ­induced hyperthermia has been 
reported in feline patients, most commonly 
after fentanyl patch application or hydro­
morphone administration.
• Opioid administration may result in altered 
GI motility (constipation), inappetence, and 
urine retention. These signs usually appear 
soon after initiation of opioid therapy and 
should resolve within 12–36 hours of 
stopping opioid administration. In the 
interim supportive care such as passing a 
urinary catheter may be necessary.
• In consultation with the pet owner, the 
veterinarian may feel the need to prescribe 
NSAIDs to a particular patient even if the 
risk for adverse events is deemed increased 
due to disease or preexisting conditions. The 
veterinarian should strive to ethically balance 
the long ­term therapeutic risk of drugs such 
as NSAIDs against the benefit of improved 
• Opioid abuse has affected all health 
professions including veterinary medicine and 
veterinarians must play active roles in combating 
abuse and misuse of opioids. With new opioid 
prescribing guidelines now published in many 
jurisdictions, veterinarians must remain up to 
date on all relevant regulations.
• Opioids can reduce the anesthetic 
requirements for most species, especially 
when combined with α2­agonists or 
acepromazine as a premedication before 
anesthesia. In humans the combination of 
certain opioids such as meperidine with 
serotonin ­altering drugs may result in toxicity 
(e.g., l ­deprenyl, amitriptyline, tramadol, trazadone) and are occasionally prescribed to 
• Concurrent glucocorticoid therapy may 
enhance NSAID toxicity.
• Other drugs that predispose animals to GI 
or renal impairment, such as aminoglycoside 
antimicrobials, should be used with caution 
when NSAIDs are also being administered.
• Adjunctive analgesic drugs (e.g., 
gabapentin, amantadine, amitriptyline, 
tramadol) may be beneficial for patients 
that have altered neuroprocessing associated 
with chronic disease changes or nervous 
system injury. To select and administer an 
adjuvant analgesic properly, the veterinarian 
should be aware of the drug’s clinical 
pharmacology. The following information 
about the drug is necessary: (1) approved 
indication, (2) unapproved indication (e.g., 
as an analgesic) widely accepted in 
veterinary medical practice, (3) common 
side effects and potentially serious adverse 
effects, (4) pharmacokinetic features, and 
(5) specific dosing guidelines for pain (see 
Appendix VII).
• Nontraditional medical treatments are 
common, but should be evaluated for safety 
and effectiveness before recommendation.
• A number of alternative treatments for 
chronic pain in dogs and/or cats are in 
various stages of development and marketing 
including mesenchymal stem cell therapy and 
anti­nerve growth factor (anti ­NGF) mono­
clonal drugs.
• Potential novel approaches to chronic pain 
currently being investigated include 
cannabidiol (CBD) which is available 
commercially and from marijuana 
dispensaries in jurisdictions where allowed. 
The FDA has decided to regulate CBD as a 
food additive and the legality of 
recommending and producing CBD for 
veterinary patients is unclear at this time. 
More research is needed before such therapies 
can be routinely recommended.
• Low­level laser therapy has gained 
popularity as an adjunctive technique to 
manage postoperative pain and facilitate 
earlier return to function following cruciate 
surgery in dogs. While this therapy may prove 
beneficial in individual cases, controlled 
studies using force plate analysis have not 
documented efficacy to date.
  FOLLOW-UP
• Frequent evaluation of analgesic drug 
effectiveness should be performed.• Patients receiving chronic analgesic 
medication, especially NSAIDs, should be 
evaluated periodically to monitor GI, liver, 
• It is the responsibility of the veterinarian to 
ensure that information about the effects of 
prescribed drugs is disseminated to clients.
Although some degree of pain is usually an 
unavoidable consequence of surgery or 
trauma, when possible, the preemptive 
administration of analgesic drugs may provide 
better pain control and reduce the potential 
for CNS wind ­up. Use of proper anesthetic 
techniques incorporating analgesic 
premedications and local and regional 
analgesic techniques where appropriate, are 
effective ways of practicing preemptive 
analgesia.
Acute pain associated with surgery or trauma 
usually resolves with tissue healing. Opioids 
may be most effective for the 12–24 hours 
following surgery, whereas NSAIDs may be 
better after that period. Some NSAIDs are 
effective analgesics immediately after 
surgery. When pain signs persist beyond the 
normal course of a few days to weeks, 
suspect persistent disease, injury, or CNS 
changes and consult an anesthesiologist or a 
board ­certified specialist trained in pain 
management for suggestions about 
appropriate therapy.
• Opioids may cause fetal respiratory 
depression following delivery. NSAIDs may 
alter maternal or fetal prostaglandin 
production, resulting in pregnancy 
• The effects on the fetus of many of the 
analgesic drugs approved for use in dogs and 
cats are not widely reported.
• CBD = cannabidiol.
• CMI = multifactorial clinical measurement 
instrument.
• COX = cyclooxygenase.
• NGF = nerve growth factor.
• NMDA =  N­methyl ­d­aspartate.
• NSAID = nonsteroidal anti ­inflammatory drug.
• American College of Veterinary Anesthesia 
and Analgesia’s position paper on treatment 
of pain in animals: http://acvaa.org/docs/
Pain_T reatment(continued)  Pain (Acute, Chronic, and Postoperative)

1024  Blackwell’s Five-Minute Veterinary Consult  
P• International Veterinary Academy of Pain 
Management: http://www.ivapm.org
• World Small Animal Veterinary Association 
(WSAVA) Global Pain Council Guidelines: 
https://wsava.org/global ­guidelines/
global ­pain­council ­guidelines/
Epstein M, Rodan I, Griffenhagen G, et al. 
AAHA/AAFP pain management guidelines 
for dogs and cats. J Am Anim Hosp Assoc 
2015, 51(2):67–84.Grimm KA, T ranquilli WJ, Lamont LA, et al. 
Veterinary Anesthesia and Analgesia: The 
Fifth Edition of Lumb and Jones. Ames, IA: 
Wiley ­Blackwell, 2015.
Renwick SM, Renwick AI, Brodbelt DC, 
et al. Influence of class IV laser therapy on 
the outcomes of tibial plateau leveling 
osteotomy in dogs. Vet Surg 2018, 
47(4):507–515.Steagall P , Robertson SA, Taylor P . Feline 
Anesthesia and Pain Management, Ames, 
IA: Wiley ­Blackwell, 2017.
Authors  Leigh A. Lamont, Kurt A. Grimm, 
and William J. T ranquilli
available onlinePain (Acute, Chronic, and Postoperative)  (continued)

Canine and Feline, Seventh Edition  1025
P
Palatal Defects
  BASICS
Communication between the nasal and oral 
cavities.
• Secondary to congenital cleft of the secondary 
palate to include the hard and/or soft palate.
• Secondary to a traumatic injury causing 
disruption of the lateral maxilla and/or 
hard palate.
• Secondary to resective surgery for neoplasms 
of the lateral maxilla and/or hard palate.
• Secondary to extraction of maxillary canine 
and rostral premolar teeth (see Oronasal Fistula).
• Gastrointestinal (oral cavity).
GENETICS
May be inherited or secondary to intrauterine 
• Primary cleft palate is an abnormality of the 
lip and premaxilla and is rarely associated 
with a palatal defect communicating with the 
• Brachycephalic breeds are predisposed to 
primary cleft palate .
• Breed predilection for congenital cleft of 
the secondary palate.
Species
Dogs more common than cats.
Brachycephalic breeds, miniature schnauzer, 
beagle, cocker spaniel, dachshund, and 
Siamese cats.
At birth in dogs with primary or secondary 
cleft palate.
N/A
SIGNS
• Difficulty nursing.
• Nasal discharge; often mucopurulent.
• Gagging when drinking water or eating.
• Poor growth.
• Lethargy and depression in chronic cases 
with severe secondary rhinitis.
• Cough in cases of secondary aspiration 
Dogs with primary or secondary cleft palate 
should be neutered since the condition is 
considered to be inherited.Historical Findings
Signs reported by the owner as above; or 
following trauma or oncologic surgery.
• Hard and/or soft plate defect 
communicating with the nasal cavity.
• Thoracic auscultation for aspiration 
• Patient is “poor doer.”
• Check for other congenital abnormalities.
CAUSES
• Failure of the palatine shelves to fuse 
during development at 25–28 days of 
• Foreign body, vehicular, or bite trauma.
• Oncologic surgery for neoplasms of the 
hard palate and/or lateral maxilla.
• Wound dehiscence following maxillofacial 
reconstructive surgery.
• Inherited (recessive or irregular dominant, 
polygenic).
• Hormonal (steroids).
• In utero  abnormality.
• Viral.
  DIAGNOSIS
Fungal or bacterial rhinitis.
• Recommended as preoperative database.
• CBC may reflect secondary chronic rhinitis 
and/or secondary aspiration pneumonia.
Consider aerobic bacterial culture and 
sensitivity of nasal tissue in cases of chronic 
rhinitis.
IMAGING
rule out aspiration pneumonia.
• MRI or CT imaging is recommended prior 
to oncologic surgery for imaging of the 
maxillary/palatal lesion.
recommended to check for distant metastasis 
before operating patients with neoplasms.
Sedated oral examination.
• Secondary rhinitis is usually self-limiting 
and resolves following surgical repair.
• Long-term (4–6 weeks) antimicrobial 
therapy based on culture and sensitivity may 
be necessary to treat the chronic rhinitis.  TREATMENT
Inpatient
Supportive preoperative care.
ACTIVITY
N/A
DIET
• Preoperative diet should be small-dog food 
“meatballs” fed by hand or a diet with a 
consistency that does not cause potential 
• Postoperative diet should be a thick liquid 
consistency for the first 2 weeks.
• A palatal defect requires surgery for repair.
• Multiple surgeries may be required to repair 
the palatal defect.
• Medical management is ineffective and is 
only indicated when multiple surgical attempts 
to repair the palatal defect have failed.
• There is a higher surgical success rate in 
older puppies.
• T ube feeding may be required for the neonate 
patient until surgery, or until the patient can eat 
a diet of appropriate consistency.
• Secondary rhinitis is expected and 
self-limiting with clinical signs more of a 
nuisance than pathologic.
• The surgical goal is to provide a soft tissue 
barrier or layer to reestablish and segregate 
the oral and nasal cavities.
• Congenital secondary cleft palate—
recommend using a sliding bipedicle flap 
repair technique or an overlapping flap repair 
• T raumatic palatal defect—recommend 
either a buccal mucosal flap repair technique 
or hard palate mucoperiosteal flap repair 
• Palatal defect following oncologic surgery—
recommend either a buccal mucosal flap 
repair technique and/or hard palate 
mucoperiosteal flap repair technique.
• Palatal defect following maxillofacial 
reconstruction dehiscence—recommend 
and/or hard palate mucoperiosteal flap repair 
• Lavage the nasal cavity before surgery to 
remove any foreign material or debris that 
may have accumulated in the nose.
• A permanent silastic obturator may used 
to occlude small palatal defects in 
refractory cases where surgery has failed 
multiple times.

1026  Blackwell’s Five-Minute Veterinary Consult  
P  MEDICATIONS
N/A unless treating preoperative rhinitis.
N/A
N/A
N/A
 FOLLOW-UP
Recommend 2- and 4-week postoperative 
examinations to determine success of the 
surgical procedure.
• Diet should be a thick liquid consistency 
for 2 weeks postoperatively.
• Chew toys and other objects are prohibited 
for the first 8 weeks postoperatively.POSSIBLE COMPLICATIONS
• Wound dehiscence and failure to repair the 
palatal defect.
• Chronic, preexisting rhinitis may require 
extended postoperative antimicrobial therapy.
• Surgery is usually successful, however 
multiple surgical procedures may be required.
• The overall prognosis is “good.”
• Rhinitis.
• Initial dietary management and feeding by 
the owner is labor intensive.
Congenital cleft palate defects are considered 
inherited and affected dogs should be 
neutered.
SYNONYMS
N/A
Search oronasal communication, oronasal 
fistula, cleft palate.
Hedlund CS. Surgery of the oral cavity and 
oropharynx. In: Fossum TW, Hedlund CS, 
Hulse DA, et al., eds., Small Animal Surgery. 
St. Louis, MO: Mosby, 1997, pp. 210–215.
Manfra Marretta S, Grove TK, Grillo JF . Split 
palatal U-flap: a new technique for repair of 
caudal hard palate defects. J Vet Dent 1991, 
8:5–8.
Smith MM. Island mucoperiosteal flap for 
repair of oronasal fistula in a dog. J Vet 
Dent 2001, 18:140–144.
Smith MM, Rockhill AD. Prosthodontic 
appliance for repair of oronasal fistula in a 
cat. J Am Vet Med Assoc 1996, 
208:1410–1412.
Author  Mark M. Smith
Consulting Editor  Heidi B. LobprisePalatal Defects  (continued)

Canine and Feline, Seventh Edition  1027
P
Pancreatitis—Cats
  BASICS
• Inflammation of the pancreas most often of 
unknown cause(s). • Acute pancreatitis—
inflammation of the pancreas that occurs 
abruptly with little or no permanent patho­
logic change. • Chronic pancreatitis—
continuing inflammatory disease that is 
accompanied by irreversible morphologic 
change such as fibrosis.
• Host defense mechanisms normally prevent 
pancreatic autodigestion by pancreatic 
enzymes, but under select circumstances these 
natural defenses fail; autodigestion occurs 
when these digestive enzymes are activated 
within acinar cells. • Local and systemic 
tissue injury is due to the activity of released 
pancreatic enzymes and a variety of 
inflammatory mediators such as kinins, free 
radicals, and complement factors that are 
released by infiltrating neutrophils and 
macrophages. The most common pathologies 
involving the feline pancreas include acute 
necrotizing pancreatitis (ANP), acute 
suppurative pancreatitis, and chronic 
nonsuppurative pancreatitis.
• Gastrointestinal (GI)—altered GI motility 
(ileus) due to regional chemical peritonitis; 
local or generalized peritonitis due to 
enhanced vascular permeability; concurrent 
inflammatory bowel disease (IBD) may be 
seen in some cats. • Hepatobiliary—lesions 
due to shock, pancreatic enzyme injury, 
inflammatory cellular infiltrates, hepatic 
lipidosis, and intra/extrahepatic cholestasis. 
Feline GI inflammatory disease (concurrent 
cholangitis ± IBD) may be seen in some cats. 
• Respiratory—pulmonary edema or pleural 
effusion. • Cardiovascular—cardiac 
arrhythmias may result from release of 
myocardial depressant factor. 
• Hematologic—activation of the coagulation 
cascade and systemic consumptive 
coagulopathy (disseminated intravascular 
coagulation [DIC]) may occur.
GENETICS
No genetic basis for disease pathogenesis in 
cats has been identified.
• T rue prevalence is unknown but this is a 
relatively common clinical disorder in cats. 
• Necropsy surveys suggest an increased 
prevalence in cats with cholangitis, and IBD. 
The unique feline pancreaticobiliary anatomy 
and intestinal microbiota likely contribute to 
multiorgan inflammatory disease in this species.
WorldwideSIGNALMENT
Species
Cat
Mean age for acute pancreatitis is 7.3 years; 
any age may be affected.
None
SIGNS
• Vague, nonspecific, and nonlocalizing signs. 
• Anorexia, lethargy, and vomiting are 
reported most frequently. • Weakness. 
• Abdominal pain. • Diarrhea—small bowel 
and large bowel diarrhea and fever are less 
common in cats than in dogs.
• Severe lethargy. • Inappetance. 
• Dehydration—common; due to GI losses. 
• Abdominal pain—recognized much less 
frequently in cats than dogs. • Mass lesions 
may be palpable. • Fever—observed in 25% 
of cats.
CAUSES
Etiology is most often unknown; possibilities 
include: • Hepatobiliary disease—both 
inflammatory and degenerative (hepatic 
lipidosis). • Pancreatic trauma/ischemia. 
• Duodenal reflux. • Drugs/toxins (organo­
phosphates). • Pancreatic duct obstruction. 
• Hypercalcemia. • Inflammatory GI disease. 
• Nutrition—excessively lean body mass is 
associated with ANP .
• Breed? • Obesity? • Organophosphate 
poisoning. • Concurrent hepatic/intestinal 
  DIAGNOSIS
• GI disease (obstruction, foreign body, 
perforation, infectious gastroenteritis, ulcer 
disease)—exclude with CBC/biochemistry/
urinalysis, diagnostic imaging, and 
paracentesis. • GI or hepatic neoplasia—
exclude with tissue biopsy. • Urogenital 
disease (pyelonephritis, prostatitis or 
abscessation, pyometra, urinary tract rupture 
or obstruction, acute renal failure)—exclude 
with CBC/biochemistry/urinalysis, urine 
culture/sensitivity, and imaging. • Hepatobiliary 
disease (cholangitis and extrahepatic biliary 
obstruction [EHBO])—exclude with CBC/
biochemistry/urinalysis, bile acids, imaging, 
and liver biopsy. • Abdominal neoplasia—
exclude with imaging and cytology or biopsy.CBC/BIOCHEMISTRY/URINALYSIS
• CBC—often reveals nonregenerative anemia 
(40%), leukocytosis (38%), and/or leukopenia 
(15%). • Serum biochemistries—often show 
prerenal azotemia; liver enzyme activities 
(alanine aminotransferase, alkaline phosphatase) 
are often elevated because of hepatic ischemia 
or exposure to pancreatic enzymes; 
hyperbilirubinemia with intra/extrahepatic 
biliary obstruction; hyperglycemia with 
necrotizing pancreatitis due to hyper­
glucagonemia; hypoalbuminemia, hyper­
cholesterolemia, and hypertriglyceridemia are 
common. Hypocalcemia is more common in 
cats than dogs, and a low ionized calcium 
concentration is a negative prognostic indicator 
in cats. • Urinalysis—increased urine specific 
gravity associated with dehydration or can be 
• Serum amylase and lipase activities are 
unreliable serologic markers—may be elevated, 
but are nonspecific; can also increase with 
hepatic, renal, or neoplastic disease in the 
absence of pancreatitis. • Serum pancreatic lipase 
immunoreactivity (fPL) is a highly sensitive and 
specific serologic marker of acute pancreatic 
inflammation. A cage ­side fPL assay (SNAP fPL) 
has been developed as a useful screening tool. 
Elevation in SNAP fPL should be followed up 
by laboratory measurement of serum Spec fPL to 
quantitate the degree of elevation.
IMAGING
• Abdominal radiographs—may include 
increased soft tissue opacity in the right cranial 
abdominal compartment; loss of visceral detail 
(“ground glass appearance”) due to abdominal 
effusion; static gas pattern in the proximal 
duodenum. • Abdominal ultrasound—
nonhomogeneous solid or cystic mass lesions 
suggest pancreatic abscess; may be a pancreatic 
mass or altered echogenicity (hypoechoic) in 
the area of the pancreas; pancreas is usually 
enlarged with irregular borders, surrounding 
mesentery may be hyperechoic due to focal 
peritonitis, may see peritoneal effusion and 
extrahepatic biliary obstruction. • fPL assay 
and pancreatic ultrasound in combination 
have the highest specificity for an antemortem 
diagnosis of acute pancreatitis.
• Ultrasound ­guided needle aspiration may 
confirm inflammation (cytology), abscess, or 
cyst. • Laparoscopy with pancreatic forceps 
biopsy for histologic diagnosis. • Histopathologic 
evaluation may miss focal or segmental 
pancreatic inflammation and results should 
be interpreted with caution.
• Gross findings (acute pancreatitis)—mild 
swelling with edematous pancreatitis. • Gross 
findings (chronic pancreatitis)—pancreas is 
reduced in size, firm, gray, and irregular; may 
contain extensive adhesions to surrounding

1028  Blackwell’s Five-Minute Veterinary Consult  
Pviscera. • Microscopic changes (acute 
pancreatitis)—include edema, parenchymal 
necrosis, hemorrhage, and neutrophilic 
cellular infiltrate with acute lesions. 
• Microscopic changes (chronic pancreatitis)—
pancreatic fibrosis around ducts, ductal 
epithelial hyperplasia, atrophy, and 
mononuclear cellular infiltrate.
  TREATMENT
• Eliminate the inciting cause (if possible). 
• Supportive care is most important.
• Aggressive IV fluid therapy. Fluid therapy 
goals—correct hypovolemia and maintain 
pancreatic microcirculation. • An isotonic 
crystalloid such as lactated Ringer’s solution or 
Normosol ­R® is the first ­choice rehydration 
fluid. • Correct initial dehydration (mL = % 
dehydration × weight in kg × 1000) and give 
over 4–6 hours. • May need colloids to improve 
pancreatic circulatory needs and prevent 
ischemia. • Following replacement of deficits, 
give additional fluids to match maintenance 
requirements (2.5 × weight in kg = mL/kg/h) 
and ongoing losses (estimated). • Potassium 
chloride (KCl) supplementation usually needed 
because of potassium loss in the vomitus; base 
potassium supplementation on measured serum 
levels (use 20 mEq of KCl/L of IV fluid if serum 
potassium levels are not known; do not 
administer faster than 0.5 mEq/kg/h).
ACTIVITY
Restrict
DIET
• Continue to feed orally unless vomiting is 
intractable; feeding maintains intestinal 
epithelial integrity and minimizes bacterial 
translocation. • Initiate enteral feeding via 
esophagostomy, gastrostomy enteral feeding 
device, or nasoesophageal tube placement. 
• NPO in animals with persistent vomiting 
for the shortest time possible; when there has 
been no vomiting for 12 hours, offer small 
volumes of water; if tolerated, begin small, 
frequent feedings of a diet that does not 
contain excessive amounts of dietary fat. Most 
nutritionists agree that excessive dietary fat 
restriction is not necessary in cats with 
• Discuss the need for extended hospitalization. 
• Discuss the expense of diagnosis and 
treatment. • Discuss possible short ­term and 
long­term complications (see Associated 
Conditions).
• May need surgery to remove pseudocysts, 
abscesses, or devitalized tissue seen with necrotizing pancreatitis. • May need 
laparotomy and pancreatic biopsy to confirm 
pancreatitis and/or rule out other, nonpancreatic 
diseases such as cholangitis, lipidosis, and/or 
IBD. • EHBO from pancreatitis may require 
ductal decompression with surgical 
correction.
• Animals with intermittent vomiting should 
be treated with antiemetics. Maropitant 
1 mg/kg SQ or PO q24h or ondansetron 
0.1–0.5 mg/kg slow IV q8–12h are good 
first­choice options. • Analgesics to relieve 
abdominal pain, e.g., butorphanol 0.1–
0.4 mg/kg SQ q6h, buprenorphine 0.005–
0.015 mg/kg IM or IV q6–12h or fentanyl 
CRI 2–4  μg/kg/h as needed. • Antibiotics 
only if evidence of sepsis from bacterial 
translocation and to prevent pancreatic 
Drugs reported to cause or exacerbate 
pancreatitis: • Anticholinergics (e.g., atropine). 
• Azathioprine. • Chlorothiazide. • Estrogens. 
• Furosemide. • Tetracycline. • l­Asparaginase.
Only use antibiotics if a clear clinical 
condition exists, such as infection.
  FOLLOW-UP
• Evaluate hydration status closely during 
first 24 hours of therapy; twice daily check 
physical examination, body weight, 
hematocrit, total plasma protein, BUN, and 
urine output. Evaluate the effectiveness of 
fluid therapy after 24 hours and adjust flow 
rates and fluid composition accordingly; 
repeat biochemistries to assess electrolyte/
acid–base status. • Watch closely for systemic 
complications involving a variety of organ 
systems; perform appropriate diagnostic tests 
as needed (see Associated Conditions). 
• Gradually taper fluids down to maintenance 
requirements if possible. Maintain oral 
alimentation or enteral nutrition as described 
above, being careful to feed diets that do not 
contain excessive amounts of dietary fat. 
• Monitor for clinical evidence of IBD and 
treat accordingly. • Monitor for progression 
to diabetes mellitus, exocrine pancreatic 
insufficiency (EPI), and/or hepatic lipidosis in 
cats with ANP .
• Weight reduction if obese. • Avoid high ­fat 
diets.POSSIBLE COMPLICATIONS
• Failed response to supportive therapy. 
• Associated conditions such as EPI, diabetes 
mellitus, and hepatic lipidosis. • Progression 
of acute pancreatitis to chronic pancreatitis.
• Guarded for most patients with ANP; cats 
with multiorgan inflammation may be less 
responsive to treatment. • More guarded to 
poor for patients with severe necrotizing 
pancreatitis, decreased ionized calcium 
fraction, hyperkalemia, fPL >20  μg/L, and 
systemic conditions.
Life-Threatening
• Pulmonary edema (e.g., adult respiratory 
distress syndrome). • Cardiac arrhythmias. 
• Peritonitis. • DIC.
Non-Life-Threatening
• Diabetes mellitus. • EPI. • Chronic 
pancreatitis. • Cholangitis and hepatic 
lipidosis. • IBD.
SEE ALSO
• Acute Abdomen. • Cholangitis/
Cholangiohepatitis Syndrome. • Exocrine 
Pancreatic Insufficiency. • Inflammatory 
Bowel Disease.
• ANP = acute necrotizing pancreatitis. 
coagulation. • EHBO = extrahepatic biliary 
obstruction. • EPI = exocrine pancreatic 
insufficiency. • fPL = feline pancreatic lipase 
immunoreactivity. • GI = gastrointestinal. 
Veterinary Information Network: http://
www.vin.com/VIN.plx
Simpson KS. Pancreatitis and triaditis in cats: 
causes and treatment. J Small Anim Pract 
2015, 56(1):40–49.
Stockhaus C, Teske E, Schellenberger K, et al. 
Serial serum feline pancreatic lipase 
immunoreactivity concentrations and 
prognostic variables in 33 cats with 
pancreatitis. J Am Vet Med Assoc 2013, 
243:1713–1718.
Xenoulis PG. Diagnosis of pancreatitis in 
dogs and cats. J Small Anim Pract 2015, 
56(1):13–26.
available onlinePancreatitis—Cats  (continued)

Canine and Feline, Seventh Edition  1029
P
Pancreatitis—Dogs
  BASICS
Inflammation of the pancreas, which may 
occur abruptly with little or no permanent 
pathologic change (acute pancreatitis) or 
occur continuously or intermittently with 
irreversible morphologic change such as 
fibrosis and atrophy (chronic pancreatitis).
• Premature intrapancreatic activation of 
zymogens results in local inflammation, 
edema, and necrosis of the pancreas and 
peripancreatic fat. • Pancreatic enzymes and 
inflammatory cytokines result in local 
(abdominal pain, vomiting) and possibly 
systemic effects (pyrexia, systemic inflamma­
tory response syndrome [SIRS], multiple organ 
dysfunction syndrome [MODS], and acute 
kidney injury [AKI]). • An autoimmune 
mechanism is suspected in English cocker 
spaniels, but remains unproven.
enhanced vascular permeability. 
• Cardiovascular—cardiac arrhythmias may 
result from release of myocardial depressant 
factor. • Hemic/lymphatic/immune—
circulating proinflammatory cytokines and 
altered endothelial cell function can result in 
complications such as SIRS and/or 
• Hepatobiliary—hepatocellular damage can 
occur secondary to regional inflammation. 
Inflammation of the pancreas can also result 
in extrahepatic bile duct obstruction. • Renal/
urologic—AKI can occur as a consequence of 
MODS. • Respiratory—regional vasculitis 
can cause pulmonary edema and/or pleural 
effusion. In severe cases, life ­threatening acute 
respiratory distress syndrome can develop.
GENETICS
A possible genetic basis has been reported in 
miniature schnauzers where mutations in the 
SPINK1  gene may confer increased susceptibility.
• Unknown, but it is a relatively common 
clinical disorder. • Up to 1% of normal dogs 
may have histologic evidence of pancreatitis.
Worldwide
Species
Dog
• Acute—miniature schnauzer, Yorkshire 
terrier, other terriers. • Chronic—cocker 
spaniel and cavalier King Charles spaniel.Mean Age and Range
Acute pancreatitis is most common in 
middle ­aged and older (>7 years) dogs.
Females overrepresented in some reports.
SIGNS
• Duration and severity of clinical signs can 
be variable, depending on the form of disease 
(acute vs. chronic). • Lethargy/anorexia. 
• Vomiting. • Weakness. • Abdominal pain 
(may be absent in chronic disease). 
• Diarrhea—small or large bowel type.
• Lethargy. • Dehydration—common; due to 
GI losses. • Abdominal pain—may adopt a 
“prayer position.” • Mass lesions may be 
palpable. • Fever—common with more severe 
acute pancreatitis. • Less common—respiratory 
distress, bleeding, and cardiac arrhythmias.
CAUSES
include: • Nutritional factors (e.g., dietary 
indiscretion, hyperlipoproteinemia). 
• Pancreatic trauma/ischemia. • Duodenal 
reflux. • Drugs/toxins. • Pancreatic duct 
obstruction. • Hypercalcemia. • Infectious 
agents—babesiosis.
• Breed—miniature schnauzers, terriers. 
• Obesity. • Prior GI disease. • Endocrine 
disease. • Dietary indiscretion—access to 
garbage or fatty foods. • Hypertriglyceridemia—  
while an association exists between hyper­
triglyceridemia and pancreatitis, a causative 
link remains unclear. • Infectious—vector ­
borne diseases (babesiosis, ehrlichiosis, and 
leishmaniasis) have been identified in some 
cases of acute pancreatitis. • Drugs/
toxins—idiosyncratic reactions to certain 
drugs (l ­asparaginase, azathioprine, 
chlorpromazine, clomipramine, potassium 
bromide) have been described. Zinc toxicosis, 
mainly from ingestion of pennies minted after 
1982, may cause pancreatitis. 
• Hypercalcemia—not specifically 
documented in dogs, but shown in multiple 
species. • Surgery—possible; secondary to 
hypoperfusion or traumatic manipulation of 
the pancreas.
  DIAGNOSIS
• GI (obstruction, septic peritonitis, ulcer, 
neoplasia)—differentiate via abdominal 
imaging. • Hepatobiliary (cholangiohepatitis, 
copper hepatopathy, mucocele, neoplasia, 
toxicity)—abdominal imaging showing 
significant gallbladder pathology, liver 
histopathology, hepatic copper quantification. • Genitourinary (AKI, pyelonephritis, 
leptospirosis, uroabdomen, pyometra, 
prostatitis)—azotemia, hyperphosphatemia, 
hyperkalemia, isosthenuric urine, active urinary 
sediment; positive urine culture; leptospiral 
microscopic agglutination titers. Abdominal 
imaging showing uterine, prostatic or urinary 
bladder pathology. • Other: 
◦ Hypoadrenocorticism—concurrent 
hyponatremia and hyperkalemia, lack of a stress 
leukogram, post adrenocorticotropic hormone 
stimulation cortisol of <1  μg/dL. ◦ Splenic 
torsion—splenomegaly with abnormal splenic 
positioning on abdominal imaging.
• CBC—hemoconcentration; inflammatory 
leukogram; thrombocytopenia. 
• Biochemistry—azotemia; increased liver 
enzyme activities; hyperbilirubinemia; 
electrolyte abnormalities associated with 
vomiting; hyperglycemia; hypoalbuminemia; 
hypercholesterolemia and hypertriglyceridemia. 
• Urinalysis—may show evidence of 
proteinuria or may be unremarkable.
unreliable serologic markers. • Serum 
pancreatic lipase immunoreactivity (cPL) is a 
sensitive and specific marker of acute pancreatic 
inflammation, although is less sensitive for 
detecting chronic pancreatic inflammation. A 
cage­side cPL assay (SNAP cPL) is a useful 
screening tool. Elevation in SNAP cPL should 
be followed up by measurement of serum Spec 
cPL to obtain a quantitative value.
IMAGING
• Abdominal radiographs—increased soft 
tissue opacity in the right cranial abdomen; 
loss of visceral detail (“ground glass 
appearance”) due to abdominal effusion; 
static gas pattern in the proximal duodenum; 
widened pyloroduodenal angle. • Abdominal 
radiographs are insensitive for pancreatitis 
and are of greater value for ruling out other 
causes of vomiting such as gastric or intestinal 
foreign bodies. • Thoracic radiographs—may 
be normal, reveal pleural effusion or 
pulmonary edema. • Abdominal ultrasound—  
imaging modality of choice; nonhomogeneous 
mass lesions suggest pancreatic abscess; 
pancreas is usually enlarged and irregular; 
may be a pancreatic mass or hypoechogenicity 
in the area of the pancreas due to edema; 
surrounding mesentery is typically hyperechoic 
due to peritonitis; may see peritoneal effusion 
and extrahepatic biliary obstruction. • cPL 
assay and ultrasound in combination have the 
highest sensitivity for an antemortem 
• Ultrasound ­guided needle ­aspiration 
cytology may confirm inflammation, abscess, 
or cyst. • Laparoscopy with pancreatic biopsy 
for histologic diagnosis. • Histopathologic

1030  Blackwell’s Five-Minute Veterinary Consult  
Pevaluation may miss focal or segmental 
pancreatic inflammation and must be 
interpreted with caution.
• Gross findings (acute)—mild swelling with 
edema; gray ­yellow areas of necrosis with 
varying amounts of hemorrhage with 
necrotizing pancreatitis. • Gross findings 
(chronic)—pancreas is reduced in size, firm, 
gray, and irregular; may contain extensive 
adhesions to surrounding viscera. • Microscopic 
changes (acute)—edema, parenchymal necrosis, 
hemorrhage, and neutrophilic cellular infiltrate. 
• Microscopic changes (chronic)— fibrosis 
around ducts, ductal epithelial hyperplasia, 
atrophy, and mononuclear cellular infiltrate.
  TREATMENT
• Inpatient management typically required. 
• Identify and remove any predisposing causes.
• Patients are at increased risk of aspiration 
pneumonia because of the concurrent 
presence of vomiting and lethargy. Therefore, 
aggressive nursing care (maintain in sternal 
recumbency with elevated head) and 
management of vomiting (antiemetics and 
promotility drugs, suction of gastric contents 
with nasogastric tube) should be instituted. 
• Aggressive IV fluid resuscitation with 
isotonic crystalloids should be administered to 
correct dehydration and encourage perfusion 
of the pancreas. • In cases where hypoalbu ­
minemia is present, colloid support with 
synthetic colloids may be needed (10–20 mL/
kg/day). • Hypokalemia is common, so IV 
potassium supplementation (not to exceed 
0.5 mEq/kg/h) is often required.
ACTIVITY
Clinical status will determine.
DIET
• Food should be withheld if patient has 
uncontrolled vomiting. • Enteral feeding 
should be encouraged as it supports enterocyte 
health, decreases bacterial translocation, and 
decreases incidence of vomiting episodes. 
• Feeding cranial to the duodenum (prepyloric) 
is safe. Therefore, if the patient is not eating 
voluntarily, nasoesophageal, nasogastric, or 
esophageal feeding tubes should be used to 
deliver low ­fat diets.
Discuss possible complications, variable 
clinical severity, and risk of recurrence 
associated with pancreatitis.
• Surgery should be avoided if possible; 
minimally invasive techniques (laparoscopy) 
or alternatives to surgery (ultrasound ­guided 
percutaneous drainage) should be used. • Surgical intervention may be indicated if 
there is suspicion of an infected necrotic area 
of the pancreas, pancreatic abscess, or 
pancreatic enlargement causing extrahepatic 
biliary obstruction.
DRUG(S) OF CHOICE (EMPHASIS 
ON ACUTE PANCREATITIS)
• Analgesic—fentanyl 2–5  μg/kg/h IV CRI; 
buprenorphine 0.01–0.02 mg/kg q6–8h IV or 
IM. • Antiemetics—maropitant 1 mg/kg SQ 
q24h; ondansetron 0.5–1.0 mg/kg IV or SQ 
q8h; metoclopramide 2 mg/kg/day IV CRI. 
• Antibiotics—usually not indicated. If bacterial 
translocation from the GI tract is suspected, 
broad ­spectrum antibiotic therapy is 
recommended (e.g., ampicillin/sulbactam 
30 mg/kg IV q8h). • Fresh frozen plasma—no 
clinical benefit has been shown. 
• Glucocorticoids—limited evidence to support 
benefit. Dogs with chronic autoimmune 
pancreatitis (English cocker spaniels are 
predisposed) may be treated with prednisone 
2 mg/kg PO as induction therapy and then 
tapered as based on cPL levels and clinical signs.
• Anticholinergics. • Azathioprine. 
• Chlorothiazide. • l­Asparaginase. 
• Meglumine antimonite. • Potassium 
bromide.
Use antimicrobials only if indicated.
N/A
  FOLLOW-UP
• The patient’s hydration status as well as 
electrolyte levels should be monitored 
frequently. Special attention should be paid to 
development of systemic signs suggestive of 
SIRS or MODS (increased respiratory rate, 
decreased urine production, bleeding). • The 
patient’s need for more or less aggressive pain 
control should be frequently reassessed. 
• Since ultrasound findings can lag behind 
clinical improvement and circulating cPL 
levels can remain increased for extended 
periods, the decision of when a patient is 
ready to be discharged from veterinary care 
should be based on the overall clinical disease 
activity.
Patients with a history of pancreatitis should 
be fed a low ­fat diet and medications known 
to be triggers for pancreatitis should be 
avoided.POSSIBLE COMPLICATIONS
• Acute complications—extrahepatic biliary 
tract obstruction, aspiration pneumonia, SIRS, 
MODS. • Chronic complications—exocrine 
pancreatic insufficiency, diabetes mellitus.
Prognosis is generally good for mild cases. 
Severe cases with development of SIRS/MODS 
have a more guarded prognosis. Negative 
prognostic factors—increases in blood urea/
creatinine, thrombocytopenia, and marked 
increases in Spec cPL have been associated with 
increased mortality. Increased alanine ami ­
notransferase has been associated with extended 
hospitalization in dogs with acute pancreatitis.
• Endocrinopathy. • Epilepsy. • Prior GI 
disease.
N/A
N/A
N/A
SYNONYMS
N/A
SEE ALSO
• Acute Vomiting. • Vomiting, Chronic
• AKI = acute kidney injury. • cPL = canine 
pancreatic lipase immunoreactivity. 
coagulation. • GI = gastrointestinal. 
• MODS = multiple organ dysfunction 
syndrome. • PLI = pancreatic lipase 
immunoreactivity. • SIRS = systemic 
 Suggested R  eading
Mansfield C. Pathophysiology of acute 
pancreatitis: potential applications from 
experimental models and human medicine to 
dogs. J Vet Intern Med 2012, 26:875–887.
Watson P . Chronic pancreatitis in dogs. Top 
Companion Anim Med 2012, 27:133–139.
Xenoulis PG, Steiner JM. Pancreas: necrosis and 
inflammation: canine. In: Washabau RJ, Day 
MJ, eds., Canine and Feline Gastroenterology. 
St. Louis, MO: Elsevier, 2013, pp. 812–821.
available onlinePancreatitis—Dogs  (continued)

Canine and Feline, Seventh Edition  1031
P
Pancytopenia
  BASICS
Simultaneous leukopenia, nonregenerative 
anemia, and thrombocytopenia; not a disease 
itself—rather, a group of laboratory findings 
that can result from multiple causes.
• Mechanisms may include decreased 
production of cells in the bone marrow or 
increased peripheral use, destruction, or 
sequestration; one or more of these 
mechanisms may occur together.
• Decreased production occurs when pluri­
potent, multipotent, or committed stem cells 
are destroyed, their proliferation or differen­
tiation is suppressed, or the maturation of 
differentiated cells is delayed or arrested.
• If pluripotent stem cells are affected, 
pancytopenia develops; if committed stem 
cells are involved, cytopenia of the specific 
cell type develops.
• Increased use and destruction of cells 
typically results in increased production in the 
bone marrow. At least 2–3 days are required 
before increased production begins to have an 
effect on peripheral blood cell counts, and 
peak output usually takes about a week; thus, 
the rate of use or destruction necessary to 
cause cytopenia is not as great during the first 
few days of disease as it is later.
• Sequestration of cells in the microcirculation, 
especially that of the spleen, intestine, and 
lungs, can cause cytopenia of the cell type 
involved.
Hemic/lymphatic/immune—bone marrow, 
spleen, lymph nodes, and other lymphocytic 
tissues; depending on the cause, these organs 
can be affected by cellular depletion, degen­
eration, necrosis, hyperplasia, dysplasia, or 
dyscrasia; changes may occur alone or in 
Pancytopenia is an uncommon occurrence 
and does not always occur with the causes 
listed (see Causes). The incidence is reported 
as 2.4% in dogs and 2.8% in cats.
Unless the cause of pancytopenia is an 
infectious agent that is localized to a certain 
region (e.g., leishmaniasis, histoplasmosis), no 
specific geographic distribution exists.
• No age, sex, or breed predilection.
SIGNS
• History reflects the underlying cause.• Lethargy, weakness, or pallor from anemia.
• Petechial hemorrhage or mucosal bleeding 
from thrombocytopenia.
• Repeated febrile episodes or frequent or 
persistent infections from leukopenia.
• Petechial hemorrhages.
• Mucosal hemorrhage (e.g., hematuria, 
epistaxis, hemoptysis, melena).
• Fever.
CAUSES
Infectious Diseases/Agents
• Feline infectious peritonitis (FIP).
• Infectious canine hepatitis (ICH).
• Canine and feline parvovirus.
• Anaplasmosis.
• Endotoxemia or septicemia.
Drugs, Chemicals, and Toxins
• Chloramphenicol.
• Second ­generation cephalosporins.
• T rimethoprim–sulfadiazine.
• Albendazole.
• Fenbendazole.
• Griseofulvin.
• Angiotensin ­converting enzyme inhibitors 
(e.g., enalapril).
• Methimazole.
• Phenobarbital.
• Phenylbutazone.
cell tumor, interstitial cell tumor).
• Chemotherapeutic drugs (azathioprine, 
carboplatin, cyclophosphamide, cytosine 
arabinoside, doxorubicin, hydroxyurea, 
vinblastine).
• Fusarium  T­2 toxin.
• Thallium.
Proliferative and Infiltrative Diseases
• Hematopoietic neoplasia (e.g., leukemias, 
lymphoma, histiocytic tumors, myelodysplastic 
• Osteosclerosis.
Immune-Mediated Diseases
• Aplastic anemia (also known as aplastic 
pancytopenia).
• Immune ­mediated hemolytic anemia and 
thrombocytopenia (when precursor cells are 
targeted by the immune system).
Vary with individual cause.  DIAGNOSIS
• Acute onset with severe clinical signs—
more consistent with conditions that 
cause necrosis, destruction, or sequestration 
of cells.
• Slow, insidious onset—more consistent 
with conditions that cause bone marrow 
Glucocorticoids often mildly to moderately 
increase the segmented neutrophil count, 
which may then obscure the presence of 
neutropenia.
Results
Phlebotomy technique may result in platelet 
clumping and hemolysis, leading to 
spuriously low platelet count and packed cell 
volume, respectively.
• Leukopenia—characterized by neutropenia 
with or without lymphopenia.
• Nonregenerative anemia—severity depends 
on duration and underlying cause.
• Blood smear evaluation—may reveal 
infectious agents (e.g., Ehrlichia  spp., 
Histoplasma capsulatum ); may reveal abnormal 
cells of any lineage, suggesting myeloprolifera ­
tive or lymphoproliferative diseases.
• Toxic changes in leukocytes—may suggest 
bone marrow injury or early release.
• Biochemical alterations—depends on organ 
and degree of involvement (e.g., increased 
liver enzymes may be seen with certain 
infectious diseases, toxins, and infiltrative 
diseases).
• Reticulocyte count—a regenerative response to 
anemia suggests destruction, use, or sequestration 
of red blood cells; a nonregenerative response 
suggests bone marrow suppression and merits 
bone marrow examination
• Immunologic tests for infectious diseases 
(e.g., FeLV, FIV, Ehrlichia  spp.); FeLV may be 
detected on immunofluorescence assay of bone 
marrow aspirate, even with negative serology.
• PCR for infectious agents.
• Bone marrow examination (aspirate smear or 
biopsy)—indicated when cause of pancytopenia 
cannot be determined with other tests.
• Hypercellular bone marrow associated with 
myelodysplastic syndrome, leukemias, 
myelophthisis, or recovery from prior 

1032  Blackwell’s Five-Minute Veterinary Consult  
P• Hypocellular bone marrow associated with 
necrosis, myelofibrosis, and suppression (e.g., 
drugs, estrogen).
• If a bone marrow aspirate cannot be 
obtained, myelofibrosis, necrosis, or marked 
hypocellularity should be suspected and a 
core biopsy should be evaluated.
Bone marrow core biopsy—may see 
replacement of normal hematopoietic tissue 
with necrotic, neoplastic, fibrous, or adipose 
tissue, depending on the specific underlying 
cause.
 TREATMENT
• Supportive treatment depends on the 
clinical situation and includes aggressive 
antibiotic therapy and blood component 
• T reatment of the underlying condition is 
T reatment should be appropriate for the 
clinical situation (i.e., the degree to which 
each cell population is decreased, presence of 
fever or infection, and established or 
suspected specific diagnoses); see specific 
causes.
• Drugs that may suppress hematopoiesis or 
trigger immune ­mediated destruction (see 
Causes).
• Nonsteroidal anti ­inflammatory drugs, 
clopidogrel, or other drugs that may interfere 
with platelet function if thrombocytopenia 
present.
Because of the patient’s potentially 
compromised immune status, glucocorticoids 
and other immunosuppressive drugs should 
be used only when necessary (e.g., when an 
immune component is suspected) and with 
extreme care and frequent monitoring.ALTERNATIVE DRUG(S)
Recombinant Hematopoietic Growth 
Factors
• Recombinant human granulocyte colony ­
stimulating factor (rhG ­CSF) 1–5  μg/kg/day 
SC; stimulates neutrophil production, may 
result in development of antibodies against 
endogenous G ­CSF .
• Recombinant human erythropoietin 
(rhEPO)—initial dosage 100 U/kg SC, 3 
times/week; stimulates erythropoiesis, may 
endogenous EPO, darbepoetin may also be 
  FOLLOW-UP
• Daily physical examination, including 
frequent monitoring of body temperature.
• Periodic CBC—frequency depends on 
severity of cytopenia, age, general physical 
condition of the patient, and underlying cause.
development of a Sertoli or interstitial cell 
tumor).
• Vaccination for infectious diseases.
patients receiving chemotherapy or radiation 
therapy.
• Hemorrhage.
• Sepsis.
• Often a guarded prognosis is warranted.
Secondary infections—in patients with 
• T ularemia, if this is the underlying cause.
• An owner can contract histoplasmosis from 
the same source as the patient.PREGNANCY/FERTILITY/BREEDING
Stress of underlying disease may cause 
abortion; see respective topics for the effects 
of different causes on pregnancy.
SEE ALSO
• Anemia, Aplastic.
• Anemia, Immune ­Mediated.
• Thrombocytopenia, Primary 
Immune ­Mediated.
• ICH = infectious canine hepatitis.
• rhEPO = recombinant human 
• rhG­CSF = recombinant human 
granulocyte colony ­stimulating factor.
(1996–2003). Vet Clin Pathol 2006, 
Weiss, DJ. New insights into the physiology 
and treatment of acquired myelodysplastic 
syndromes and aplastic pancytopenia. Vet 
33(6):1317–1334.
Weiss DJ, Evanson OA. A retrospective study 
of feline pancytopenia. Comp Haematol Int 
2000, 1:50–55.
Weiss DJ, Evanson OA, Sykes J. A retrospective 
study of canine pancytopenia. Vet Clin Pathol 
1999, 28:83–88.
available onlinePancytopenia  (continued)

Canine and Feline, Seventh Edition  1033
P
Panniculitis/Steatitis
  BASICS
OVERVIEW
Inflammation of the subcutaneous fat tissue.
Species
Steatitis—predominantly cats, but can occur 
in dogs with concurrent diseases.
• Panniculitis—any age. • Steatitis—young 
to middle-aged cats; older dogs.
SIGNS
• Uncommon in dogs and cats. • Single or 
multiple subcutaneous nodules or draining 
tracts. • May be painful and fluctuant to 
firm. • Nodules—few millimeters to several 
centimeters in diameter. • Involved fat may 
necrose. • Exudate—usually a small amount 
of oily discharge; yellow-brown to bloody. 
• Multiple lesions (dogs and cats)—systemic 
signs common (e.g., anorexia, pyrexia, 
lethargy, and depression).
• Infectious—bacterial, fungal (deep mycosis 
or dermatophyte), opportunistic mycobacteria, 
Nocardia , viral. • Immune-mediated—lupus 
panniculitis, erythema nodosum, vasculitis, or 
drug reaction. • Idiopathic—sterile nodular 
panniculitis, thromboembolism, sterile 
pyogranulomatous dermatitis and panniculitis. 
• T rauma. • Neoplastic—multicentric mast 
cell tumors, cutaneous lymphoma, pancreatic 
carcinoma. • Foreign bodies. • Post-
injection—corticosteroids, vaccines, other 
subcutaneous injections. • Nutritional—
vitamin E deficiency in cats, oily fish-based 
diet (steatitis).
  DIAGNOSIS
• More common than sterile/immune-
mediated panniculitis. • Deep pyoderma. 
• Feline infectious peritonitis.
Cutaneous Cyst
• Usually nonpainful, noninflamed. • Well 
demarcated.
Lipoma
• Soft; usually well demarcated. • No 
inflammation or draining tracts. • Usually 
solitary.Mast Cell Tumors/Epitheliotropic 
Lymphoma
• Multifocal. • Often erythematous. 
• Variable presentations.
Sterile Nodular Panniculitis
Diagnosis made by ruling out other causes of 
panniculitis.
• Panniculitis—no abnormalities. • Steatitis 
and panniculitis (occasional)—moderate to 
severe neutrophilia with mild eosinophilia; 
mild to moderate leukocytosis; mild 
nonregenerative anemia; hypoalbuminemia 
and proteinuria, possible hypocalcemia.
• Antinuclear antibody—lupus panniculitis. 
• Serum protein electrophoresis. • Serum 
lipase/amylase levels. • Feline leukemia virus/
feline immunodeficiency virus.
IMAGING
• Abdominal ultrasound: ◦ Panniculitis—
pancreatitis may be a contributing factor. 
◦ Steatitis—may see mottled subcutaneous, 
inguinal, or falciform fat; loss of contrast in 
abdominal cavity.
• Aspirates and impression smears: 
◦ Pyoderma—numerous neutrophils and 
variable numbers of mononuclear cells and 
bacteria. ◦ Fungal infections—fungal 
organisms and variable numbers of 
mononuclear cells may be noted. 
• Blastomycosis—urine antigen testing. 
• Bacterial culture and susceptibility testing 
(tissue)—identify primary or secondary 
bacterial infection. • Fungal and 
opportunistic mycobacteria culture (tissue). 
• Biopsy with negative cultures for diagnosis 
of sterile nodular panniculitis. • Special stains 
of histopathologic samples—may help 
identify causative agent.
• Surgical excisional biopsies—more accurate 
than punch biopsy specimens in most cases. 
• Panniculitis—lobular or diffuse infiltrate 
(granulomatous, pyogranulomatous, 
suppurative, eosinophilic, necrotizing, or 
fibrosing) of panniculus; may identify if vasculitis 
present. • Steatitis—lumpy, granular fat, normal 
to yellowish-orange coloration of body fat.
  TREATMENT
Diet
Steatitis—remove fish products from diet; 
feed nutritionally complete, balanced, 
commercially prepared food; may require 
parenteral feeding (e.g., PEG tube, 
esophagostomy feeding tube).  MEDICATIONS
Positive culture results require appropriate 
antibacterial, antifungal, or antimycobacterial 
• Systemic treatment with corticosteroids; 
prednisolone 2.2 mg/kg daily in dogs or 
4.4 mg/kg daily in cats: taper based on response: 
may require low dose to maintain remission. 
• Azathioprine (dogs: 1 mg/kg PO daily 
initially)—used with corticosteroids if 
insufficient response. • Oral vitamin E 200 IU 
q12h <10 kg, 400 IU q12h >10 kg. 
• Cyclosporine beneficial in some dogs (initially 
5 mg/kg q24h for 4–8 weeks, then tapered).
Steatitis
Oral vitamin E 200 IU q12h <10 kg, 400 IU 
q12h >10 kg; corticosteroids at an anti-
inflammatory dosage; S-adenosylmethionine 
PO on an empty stomach.
  FOLLOW-UP
• Depends on underlying etiology type and 
duration of treatment. • Monitor CBC, 
platelet count, chemistry profile, and 
urinalysis/urine bacterial culture and 
sensitivity if immunosuppressive agents or 
long-term corticosteroids prescribed.
• Pancreatic carcinoma. • Chylous ascites. 
• PEG tube = percutaneous endoscopically 
placed gastrostomy tube.
3rd ed. Hoboken, NJ: Wiley-Blackwell, 2018.

1034  Blackwell’s Five-Minute Veterinary Consult  
PPanosteitis
  BASICS
A self-limiting, painful condition of uncertain 
etiology that typically affects juvenile dogs of 
large to giant breeds. It is characterized 
clinically by lameness and pain on palpation 
of one or more long bones, and radiograph -
ically by increased density of the marrow 
cavity of affected long bones.
• Cause unknown.
• Attempts to isolate microorganisms have failed.
• Suggested metabolic, allergic, or endocrine 
aberrations are without support.
• Pain may be associated with the disturbance 
of endosteal and periosteal elements, vascular 
congestion, or high intramedullary pressure.
Musculoskeletal—causes lameness of variable 
intensity; may affect a single limb or progress 
to a shifting leg lameness.
GENETICS
• No proven transmission.
• Predominance of German shepherd dogs in 
the affected population strongly suggests an 
inheritable basis.
Estimated at 2.6 per 1000 patients.
N/A
Species
Dog
• Large- to giant-breed dogs are more 
• German shepherd dogs and German 
shepherd dog mixes are more commonly 
affected.
• Usually 5–12 months of age.
• As young as 2 months and as old as 5 years.
Males affected more than females by a ratio of 
4:1.
SIGNS
Lameness evaluation—if no distinct 
abnormalities noted on physical examination 
or radiographs, repeat examination and 
radiographs 4–6 weeks later.
• No associated trauma.
• Lameness of varying intensity; often 
involves the forelimbs initially; may affect the 
hind limbs; may see shifting leg lameness; 
may be non-weight-bearing.• Mild depression, inappetence, fever, and 
weight loss may be seen with severe disease.
• Pain on deep palpation of the long bones 
(diaphysis) in an affected limb; distinguishing 
characteristic; palpate firmly along the entire 
shaft of each bone while carefully avoiding 
any pinching of nearby muscle.
• Bones—ulna most commonly affected; may 
affect radius, humerus, femur, and tibia (in 
decreasing order of frequency) either 
concurrently or subsequently.
• May note low-grade fever or lethargy with 
severe disease.
• May see muscle atrophy.
CAUSES
Unknown
Purebred German shepherd dog or German 
shepherd dog mix.
  DIAGNOSIS
• Always consider the diagnosis with 
lameness in a young large- and giant-breed 
dogs; especially in German shepherd dog or 
German shepherd dog mix.
• May occur alone or with other juvenile 
orthopedic diseases.
• Osteochondritis dissecans.
• Fragmented medial coronoid process.
• Un-united anconeal process.
• Fractures and ligamentous injuries from 
unobserved trauma.
• Shifting leg lameness—immune-mediated 
arthropathy; Lyme disease; bacterial 
• Bacterial osteomyelitis.
• May note eosinophilia early in disease.
N/A
IMAGING
• Radiographic densities within the medulla 
of long bones are characteristic finding.
• Early, middle, and late radiographic lesions.
• Early—trabecular pattern of the ends of the 
diaphysis becomes more prominent; may 
appear blurred; may see granular opacities.
• Middle—patchy sclerotic opacities first 
around the nutrient foramen and later 
throughout the diaphysis; widened cortex; 
thickened periosteum with increased opacity.
• Late—during resolution, diminished overall 
opacity of the medullary canal (toward 
normal); a coarse trabecular pattern and some granular opacity may remain; may be a period 
in which the medullary canal becomes more 
lucent than normal.
• Bone scintigraphy may reveal subtle lesions 
that later become more apparent on follow- 
up radiographs.
Bone biopsy is occasionally indicated to rule 
out neoplasia and bacterial or fungal 
osteomyelitis that have similar radiographic 
appearances.
• Biopsy or necropsy are rarely performed 
because of excellent prognosis for recovery.
• No gross pathologic lesions.
• Degeneration of the marrow adipocytes 
surrounding the nutrient foramen followed 
by proliferation of vascular stromal cells 
within the marrow sinusoids.
• Osteoid formation and endosteal new bone 
formation—progress proximally and distally.
• Vascular congestion—may accompany the 
proliferation of new bone, secondarily 
stimulating endosteal and periosteal reaction.
• Remodeling of the endosteum—occurs 
during resolution; reestablishes normal 
endosteal and marrow architecture.
  TREATMENT
Typically treat as an outpatient.
Maintenance and replacement fluid therapy is 
occasionally needed if prolonged periods of 
inappetence and pyrexia.
ACTIVITY
• Limit activity to lessen pain; not shown to 
hasten recovery.
• Moderate to severe disease can cause pain that 
limits movement, leading to muscle atrophy.
• Warn client that patient may develop other 
juvenile orthopedic diseases.
• Inform client that signs of pain and 
lameness may last for several weeks.
• Warn client that recurrence of clinical signs 
is common up to 2 years of age.
N/A
(NSAIDs):
◦ Minimize pain; decrease inflammation.
◦ Symptomatic therapy has no bearing on 
the duration of the disease.

Canine and Feline, Seventh Edition  1035
P
◦ Carprofen 2.2 mg/kg PO q12h or 4.4 
mg/kg PO q24h.
◦ Deracoxib 1–2 mg/kg PO q24h, 
chewable.
◦ Etodolac 10–15 mg/kg PO q24h.
◦ Firocoxib 5 mg/kg PO q24h.
◦ Meloxicam—load 0.2 mg/kg PO, then 
◦ Tepoxalin—load 20 mg/kg, then 10 mg/
kg PO q24h.
• Glucocorticoids:
◦ May give anti-inflammatory dosage—
prednisone 0.5–1 mg/kg PO.
◦ Potential side effects well documented.
◦ Goal for chronic use—low-dose and 
alternate-day therapy.
ulceration, hepatotoxicity, or nephrotoxicity.
ulceration; consider appropriate washout 
another.
N/A
  FOLLOW-UP
Recheck lameness every 2–4 weeks to detect 
more serious concurrent orthopedic 
problems.PREVENTION/AVOIDANCE
N/A
N/A
• Self-limiting disease.
• T reatment is symptomatic and appears to 
have no influence on duration of clinical 
signs.
• Multiple limb involvement is common.
• Lameness typically lasts from a few days to 
several weeks; may persist for months; may 
recur.
• Occasional case has unrelenting pain and 
lameness that is unresponsive to therapy. 
Euthanasia has been recommended in these 
dogs.
N/A
Typically affects immature and young dogs
N/A
Females reported to be more susceptible to 
panosteitis during estrus; no proven 
relationship to reproductive hormones or 
SYNONYMS
• Enostosis.
• Eosinophilic panosteitis.
• Fibrous osteodystrophy.
• Juvenile osteomyelitis.ABBREVIATIONS
drug.
Halliwell WH. T umorlike lesions of bone. In: 
Bojrab MJ, ed., Disease Mechanisms in 
Small Animal Surgery, 2nd ed. Philadelphia, 
PA: Saunders, 1993, pp. 932–933.
LaFond E, Bruer GJ, Austin CC. Breed 
susceptibility for developmental diseases in 
dogs. J Am Anim Hosp Assoc 2002, 
38:467–477.
Muir P , Dubielzig RR, Johnson KA. 
Panosteitis. Compend Contin Educ Pract 
Vet 1996, 18:29–33.
Piermattei DL, Flo GL, DeCamp CE. 
Miscellaneous conditions of the 
musculoskeletal system. In: Handbook of 
Small Animal Orthopedics and Fracture 
Repair, 4th ed. Philadelphia, PA: Saunders, 
2006, pp. 775–778.
Schwarz T, Johnson VS, Voute L, Sullivan M. 
Bone scintigraphy in the investigation of 
occult lameness in the dog. J Small Anim 
Pract 2004, 45:232–237.
orthopedic diseases: Panosteitis, Legg-Calvé-
available online(continued)  Panosteitis

1036  Blackwell’s Five-Minute Veterinary Consult  
PPanting and Tachypnea
  BASICS
• Tachypnea—increased respiratory rate.
• Panting—rapid, shallow, open-mouth 
breathing that is usually not associated with 
gas exchange issues.
• Respiratory rate, rhythm, and effort are 
controlled by the respiratory center in the 
brainstem in response to numerous afferent 
pathways, both central and peripheral in 
origin. These include the cerebral cortex, 
central chemoreceptors, peripheral chemo -
receptors, stimulation of mechano  receptors in 
the airways that sense lung inflation and 
deflation, stimulation of irritant receptors of 
the airways, stimulation of C-fibers in the 
alveoli and pulmonary blood vessels that 
sense interstitial congestion, and 
baroreceptors that sense changes in blood 
pressure.
• Tachypnea and panting can occur in 
response to stimulation of any of the above 
receptor pathways.
• Dog and cat; no age, or sex predilection.
• Older, large-breed dogs predisposed to 
panting associated with laryngeal paralysis.
• Brachycephalic dogs prone to panting due 
to upper airway obstruction.
SIGNS
• Patients with primary respiratory or cardiac 
disease usually have associated coughing or 
exercise intolerance.
• Nonrespiratory causes—clinical complaints 
associated with the primary disease, e.g., 
polyuria, polydipsia, polyphagia (PU/PD/PP) 
with hyperadrenocorticism, intermittent signs 
of systemic hypertension with 
pheochromocytoma.
• Brachycephalic syndrome (stenotic nares, 
stertorous respirations associated with soft 
palate elongation or saccular eversion) may be 
observed.
• Stridor can be evident with upper airway 
diseases.
crackles on auscultation; harsh or moist lung 
sounds common, may be normal.
murmur or arrhythmia, tachycardia, gallop 
sound, hypothermia, pale mucous membranes, 
poor capillary refill time.• Pleural space disease—diminished breath 
unilaterally—space-occupying lesions, 
pyothorax, chylothorax.
• Thoracic wall disease—can have paradoxical  
respiratory pattern, visible and/or palpable 
trauma.
• Nonrespiratory diseases—findings will 
depend on the other diseases, e.g., pale 
mucous membranes if anemic, hepatomegaly 
with hyperadrenocorticism.
• Other signs could indicate trauma.
CAUSES
Panting
• Pain, anxiety, hyperthermia, fever.
• Laryngeal disease.
• CNS disease causing abnormal ventilatory 
control.
• Cardiovascular compromise (shock), 
hypertension, arrhythmia.
• Drug therapy (opioids)
• Hyperadrenocorticism, corticosteroid therapy.
• Can be a normal behavioral pattern in some 
dogs.
Tachypnea
• Hypoxemia, hypercapnia, hypotension, 
hyperthermia/fever, anemia, acidosis, systemic 
inflammatory response syndrome (SIRS)/
sepsis, brainstem disease.
• Upper airway/larynx—elongated soft 
palate, laryngeal paralysis, edema, collapse, 
foreign body, neoplasia, granuloma, stenosis, 
inflammation, trauma, webbing.
atrium, heart-base tumors).
• Lower airway disease—allergic disease, 
inflammation, infection ( Mycoplasma ), 
parasites, neoplasia.
• Pulmonary parenchymal disease—edema 
(cardiogenic or noncardiogenic), pneumonia 
or pneumonitis, neoplasia (primary or 
metastatic), hemorrhage, fibrosis, lung lobe 
torsion, atelectasis.
• Pulmonary thromboembolism associated 
with—immune-mediated hemolytic anemia 
(IMHA), hyperadrenocorticism, pulmonary 
thromboembolism (PLE), protein-losing 
nephropathy (PLN), cardiac disease, neoplasia, 
heartworm disease.
• Pleural space disease—pleural effusion or 
pneumothorax, neoplasia, diaphragmatic 
hernia.
• Abdominal distention—organomegaly; 
neoplasia, pregnancy; obesity; ascites; gastric 
dilatation, torsion.
• CNS disease—compression or infarct near 
the respiratory center.• Metabolic acidosis—diabetic ketoacidosis, 
lactic acidosis, uremia, renal tubular acidosis, 
diarrhea.
  DIAGNOSIS
• Tachypnea without respiratory distress—
may be a nonrespiratory problem.
• Stertor and stridor are features of upper 
airway disease—auscultation over the trachea 
can help delineate upper airway noises from 
lower airway noises.
• Thoracic auscultation and percussion—
most useful for distinguishing pleural disease 
(dampened lung sounds, dull percussion) 
from parenchymal disease (normal, harsh or 
moist lung sounds, crackles on auscultation).
• Wheezes on auscultation are suggestive of 
narrowed lower airway (bronchi, bronchioles).
• Crackles on auscultation are features of 
pulmonary parenchymal diseases.
• Congestive heart failure—murmur, tachycardia, 
poor pulse quality, jugular pulses, 
hypothermia.
• Anemia—can cause nonrespiratory tachypnea.
pneumonitis, pyothorax, or nonrespiratory 
causes (SIRS, sepsis).
predisposes to pulmonary thromboembolism 
(PTE); alternatively, could indicate iron-
• Sodium:potassium ratio <27—can be seen 
• High alkaline phosphatase—hyperadreno -
corticism predisposes to panting and PTE.
• Hypoproteinemia—may suggest protein-
losing disease that can predispose to PTE.
• Azotemia—if severe can lead to uremic 
• Hyperglycemia, glucosuria, and 
ketonuria—could indicate ketoacidosis as 
cause of tachypnea.
• Fecal examinations for parasites if indicated.
or adrenocorticotropic hormone stimulation 
test to assess adrenal cortical function, if 
leukemia virus, feline immunodeficiency virus.
• Pulse oximetry or arterial blood gas—can 
help differentiate pulmonary from 
nonrespiratory causes.

Canine and Feline, Seventh Edition  1037
P
• Hemoglobin saturation with oxygen <95% 
supportive of hypoxemia.
• Pao2—partial pressure of oxygen dissolved 
in arterial blood; normoxemia: Pao2 
80–120 mmHg (room air, sea level), 
hypoxemia: Pao2 <80 mmHg; FIo2—fraction 
of inspired oxygen ranges from 0.21 (room 
air) to 1.0; Pao2/FIo2 ratio—measure of lung 
efficiency during oxygen therapy; Pao2/FIo2 
≥400—normal lung efficiency; 300–400—
mild insufficiency; 200–300—moderate 
insufficiency; <200—severe insufficiency. 
Reduction in lung efficiency can be due to 
venous admixture, hypoventilation, low 
inspired oxygen.
• Paco2 or Pvco2—partial pressure of CO2 
dissolved in arterial or venous blood; measure 
of ventilation; normal 30 mmHg < Pco2 
<40 mmHg. Hypercapnia = hypoventilation =   
decreased alveolar minute ventilation. 
Hypocapnia = hyperventilation = increased 
alveolar minute ventilation. Hypoventilation 
can be due to airway obstruction, pleural 
space disease, thoracic wall disease and 
abdominal distention; respiratory muscle 
fatigue from a prolonged period of tachypnea 
can lead to hypoventilation.
• Blood gas may reveal metabolic acidosis as a 
cause.
• Coagulation testing—if suspect 
hemothorax and/or pulmonary hemorrhage.
IMAGING
Cervical and Thoracic Radiography
• Increased density could suggest edema or 
soft tissue mass lesion. Also can see soft palate 
elongation, large airway narrowing, lympha -
denopathy, intraluminal abnormalities.
• Lower airway disease —bronchial 
thickening, middle lung lobe consolidation 
(cats), atelectasis, hyperinflation and 
• Pneumonia —alveolar infiltrates; aspiration 
pneumonia usually cranioventral distribution 
or middle lobe affected.
• Cardiogenic pulmonary edema—enlarged 
cardiac silhouette, pulmonary venous 
be of any distribution in cats.
• Noncardiogenic pulmonary edema —
usually caudodorsal distribution. Acute 
respiratory distress syndrome (ARDS)—
diffuse, symmetrical alveolar infiltrates.
• Pulmonary vascular abnormalities—PTE, 
• Pleural space disease—pneumothorax, pleural 
effusion, mass lesions, diaphragmatic hernias.
• Thoracic wall disease—rib fractures, 
Thoracic Ultrasonography
• Evaluation of distribution of pleural 
effusion (excellent as guide for 
thoracocentesis), pneumothorax (absence of “glide sign”), and parenchymal disease 
(presence of “comet tail” artifact).
• Pulmonary mass identification—guide 
fine-needle aspiration; mediastinal evaluation.
Evaluate cardiac function and chamber size if 
cardiogenic pulmonary edema or pleural 
effusion suspected; elevated pulmonary artery 
pressure and right ventricular overload with 
ventricular septal flattening can support 
diagnosis of PTE; visualize heart-based 
masses, rule out pericardial effusion.
Evaluation of abdominal distension; assess 
adrenal gland size.
Evaluate tracheal and bronchial collapse; 
evaluate diaphragmatic function.
CT
Airway, pulmonary parenchymal, and pleural 
space disease can be evaluated; can detect 
lesions not clearly defined on radiographs.
Pulmonary Vascular Angiography
Gold standard for diagnosis of PTE.
Ventilation Perfusion Scintigraphy
Abnormal perfusion scan is considered 
Other
May need CNS imaging.
• Pulse oximetry— Spo2; peripheral capillary 
hemoglobin oxygen saturation. The relation -
ship between Pao2 and Spo2 is defined by the 
oxygen hemoglobin dissociation curve; Pao2 
of 60 mmHg =  Spo2 of 90%; Pao2 of 
80 mmHg =  Spo2 of 95%; Pao2 of 
>100 mmHg =  Spo2 of 100%. Below 95%, 
small changes in Spo2 signify large changes in 
Pao2. Spo2 measurements in animals on high 
tracheoscopy—to evaluate laryngeal function 
and visualize foreign bodies and masses; visualize 
caudal nasopharyngeal region with flexible 
endoscope or spay hook and dental mirror.
airways; take biopsies; perform bronchoalveolar 
lavage for cytology and culture.
  TREATMENT
• Inpatient care if life-threatening; therapy 
depends on underlying cause.
• Administer oxygen and see if tachypnea 
resolves—this would be supportive of a 
primary respiratory problem.
• Upper airway disease—use sedation to reduce respiratory effort. Check body 
temperature frequently and actively cool 
patients as needed. Severe upper airway disease 
requires intubation to stabilize; if the problem 
cannot be immediately cured, placement of a 
temporary tracheostomy tube is indicated. 
Remove foreign bodies; perform surgical 
excision/biopsy of masses, surgical correction 
for laryngeal paralysis and brachycephalic 
syndrome; give anti-inflammatory 
medications for laryngeal edema.
positive-pressure ventilation if oxygen therapy 
alone is not adequate to stabilize the patient.
• Pleural space disease—thoracentesis for air 
and fluid. Place a chest tube if repeated chest 
taps are needed to keep patient stable.
• Abdominal distention—drain ascites only 
as needed to keep the patient comfortable; 
relieve gastric distention.
• Nonrespiratory diseases—treat primary 
problem.
E-collar covered in plastic wrap, mask, or 
flow-by. Humidify oxygen source if giving 
oxygen therapy for more than a few hours.
• Monitor temperature regularly, as hyper -
thermia will worsen respiratory difficulty.
DIET
Weight-reducing diet if obesity is a contribut-
ing cause.
rapid IV induction is important. Have 
multiple sizes of endotracheal tubes available 
if upper airway obstruction is suspected.
• If laryngeal paralysis or brachycephalic 
syndrome is suspected, prepare for surgical 
correction at the time of diagnosis. Warn 
owners of increased likelihood of aspiration 
pneumonia in dogs with laryngeal disease.
  FOLLOW-UP
N/A(continued)  Panting and Tachypnea

1038  Blackwell’s Five-Minute Veterinary Consult  
P  MISCELLANEOUS
SEE ALSO
• Pneumonia chapters.
• Pulmonary Edema, Noncardiogenic.ABBREVIATIONS
• ARDS = acute respiratory distress syndrome.
• IMHA = immune-mediated hemolytic anemia.
• PTE = pulmonary thromboembolism.
• PU/PD/PP = polyuria, polydipsia, polyphagia.
• SIRS = systemic inflammatory response 
syndrome.
Hackner SG. Panting. In: King LG, ed., 
Textbook of Respiratory Disease in Dogs 
and Cats. Philadelphia, PA: Saunders, 2004, 
pp. 46–48.
Lee JA. Nonrespiratory look-alikes. In: 
Animal Critical Care Medicine, 2nd ed. 
Philadelphia, PA: Saunders Elsevier, 2015, 
pp. 157–160.Mandell DC. Respiratory distress in cats. In: 
King LG, Textbook of Respiratory Disease 
in Dogs and Cats. Philadelphia, PA: 
Saunders, 2004, pp. 12–17.
O’Sullivan ML. Tachypnea, dyspnea, and 
respiratory distress. In: Ettinger SJ, Feldman 
EC, Cote E, eds., Textbook of Small Animal 
Saunders Elsevier, 2017, pp. 115–119.
Acknowledgement  The author and editors 
acknowledge the prior contribution of Kate 
Hopper.Panting and Tachypnea  (continued)

Canine and Feline, Seventh Edition  1039
P
Papillomatosis
  BASICS
OVERVIEW
Cutaneous mucous membrane lesions of dogs 
and cats caused by various papillomaviruses.
Dogs
• Puppies and young adult dogs—oral 
papillomatosis, venereal papillomatosis, 
multiple papillomas of the footpad, cutaneous 
inverted papillomas, canine pigmented viral 
plaques (breed predisposition). • Older 
dogs—exophytic cutaneous papillomas, 
cutaneous inverted papillomas. • Miniature 
schnauzers and pugs—pigmented viral 
plaques; associated with immunosuppression 
in other breeds.
Cats
• More common in older cats; associated 
with immunocompromise (e.g., feline 
immunodeficiency virus [FIV]). • Feline 
sarcoids—younger cats, especially with 
outdoor exposure.
SIGNS
Dogs
• Cutaneous papillomas—pedunculated, 
fronds of epithelium, up to 1 cm in diameter. 
• Canine oral papillomatosis/papillomavirus 
(COPV)—oral mucosa, hard palate, 
epiglottis; may interfere with prehension, 
swallowing; trauma results in halitosis and 
ptyalism; may be confined to genital or eyelid 
regions. • Cutaneous inverted papillomas—
less common, multiple lesions found with a 
central pore; on ventral abdomen; caused by 
distinctly different papillomavirus from 
COPV. • Multiple papillomas affecting 
footpads in younger dogs—firm, 
hyperkeratotic lesions causing discomfort, 
lameness. • Canine pigmented viral 
plaques—miniature schnauzers, pugs; Boston 
terriers, French bulldogs; rarely transform to 
squamous cell carcinoma (SCC); ventral 
abdomen, inner thigh region.
Cats
• Feline cutaneous papillomas—rare. • Feline 
viral plaques—more common; may progress 
to bowenoid in situ  carcinoma (BISC) or 
invasive carcinoma. • Feline sarcoid 
lesions—uncommon. • Cats 10 years or 
older; other systemic disease causing 
immunosuppression (e.g., FIV).
• Oral papillomas affecting naive dogs and 
recovered animals develop lifelong immunity. 
• Dogs—cutaneous papillomas may involve 
cell-mediated immunologic defects. • Older 
and/or immunosuppressed cats develop plaques and BISC. • Canine pigmented viral 
plaques—strong breed predisposition.
  DIAGNOSIS
Dogs
• Oral cavity, oropharynx—fibromatous 
epulis, transmissible venereal tumor, SCC. 
• Cutaneous—sebaceous hyperplasia, 
acrochordon. • Pigmented plaque—
melanocytoma. • Inverted—infundibular 
keratinizing acanthoma.
Cats
• Eosinophilic granuloma. • Actinic keratoses 
• Cutaneous feline leukemia virus (FeLV) 
lesions. • Multicentric SCC in situ . • SCC.
Normal
Cats—FeLV, FIV .
• Gross lesions have a typical appearance. 
• Biopsy for histopathology; 
immunohistochemistry demonstrates viral 
antigens within lesions; PCR not definitive.
• Dependent upon syndrome; all lesions 
share cytopathic effects of papillomavirus 
infection: hyperkeratosis, acanthosis, 
koilocytes in stratum spinosum, abnormal, 
large keratohyalin granules in stratum 
granulosum. • Viral pigmented plaques may 
lack koilocytes and viral inclusion bodies.
  TREATMENT
• Usually regress spontaneously (especially 
oral forms). • Surgery if needed (excision, 
cryosurgery, or electrosurgery). • Persistent 
disease (dogs)—COPV vaccine reported to 
induce epithelial tumors and SCC at 
vaccination sites; latency period 11–34 
months; autogenous vaccination: treatment 
controversial. • Cats—diagnosis for visceral 
diseases, causes of immunosuppression.
• α-Interferon—20,000iu PO q24h; various 
reports of efficacy for the treatment of 
persistent COPV but studies are lacking 
regarding dosage and protocol for 
administration. • Imiquimod—applied to lesions 3 times/week for 4 weeks. 
• Azithromycin 10 mg/kg PO q24h × 14 days.
Imiquimod—human exposure potential; 
causes severe localized reaction; use with 
caution at mucocutaneous junctions.
  FOLLOW-UP
Monitor for signs of malignant 
transformation to SCC.
• Separate dogs with oral papillomas from 
susceptible animals. • Commercial kennels—
may consider autogenous vaccination.
• Dogs—prognosis good; incubation period 
1–8 weeks; regression usually 1–5 months; 
lesions persist 24 months or more. • Cats—
long-term prognosis for plaques and BISC 
depends on concurrent diseases.
N/A
Viral strain dependent.
Papillomaviruses—species specific.
• Venereal lesions may preclude breeding. 
• T ransmission of viral infection likely; 
especially if active lesions present.
SYNONYMS
Bowen’s disease = BISC.
SEE ALSO
Dermatoses, Viral (Nonpapillomatosis).
• BISC = bowenoid in situ  carcinoma. 
• COPV = canine oral papillomatosis/
papillomavirus. • FeLV = feline leukemia 
virus. • FIV = feline immunodeficiency virus. 
• SCC = squamous cell carcinoma.
Resnick

1040  Blackwell’s Five-Minute Veterinary Consult  
PParalysis
  BASICS
• Paresis—weakness of voluntary movement. 
• Paralysis—lack of voluntary movement. 
• Quadriparesis (tetraparesis)—weakness of 
voluntary movements in all limbs. 
• Quadriplegia (tetraplegia)—absence of all 
voluntary limb movement. • Paraparesis—
weakness of voluntary movements in pelvic 
limbs. • Paraplegia—absence of all voluntary 
pelvic limb movement. • Schiff–Sherrington 
syndrome—may occur with severe spinal cord 
trauma below T2. Patient presents paraplegic, 
in lateral recumbency with extension of front 
limbs and neck. However front limb function 
is normal on neurologic examination. 
Prognosis based on presence or absence of 
pain perception in pelvic limbs. • Spinal 
shock—may occur with severe spinal cord 
trauma, usually near the thoracolumbar spine. 
Initially the paralyzed pelvic limbs are areflexic 
but become hyperreflexic (and more indicative 
of a T3–L3 lesion localization) within minutes 
to a few hours after the trauma.
• Weakness—caused by lesions in the upper 
motor neuron (UMN) or lower motor neuron 
(LMN) systems. • UMN system—cell bodies 
or nuclei located within the brain are 
responsible for initiating voluntary movement; 
axons from these cell bodies form tracts 
(rubrospinal, corticospinal, vestibulospinal, 
reticulospinal) that descend from the brain to 
synapse on the interneurons in the spinal cord. 
Interneuronal axons synapse on large alpha 
motor neurons in the ventral gray matter of 
the spinal cord; these are cell bodies of origin 
for the LMN system, which is responsible for 
spinal reflexes. • LMN system—collections of 
lower motor neurons in the cervical and 
lumbar intumescences give rise to axons that 
form the ventral nerve roots, spinal nerves, and 
(ultimately) the peripheral nerves that 
innervate limb muscles. • Evaluation of limb 
reflexes—determines which system (UMN or 
LMN) is involved. • UMN and their axons—
have inhibitory influence on the large alpha 
motor neurons of the LMN system; maintain 
normal muscle tone and normal spinal reflexes. 
• If UMN is injured, spinal reflexes are no 
longer inhibited or controlled and spinal 
reflexes become exaggerated or hyperreflexic. 
• If LMN system is injured, spinal reflexes 
cannot be elicited (areflexic) or are reduced 
(hyporeflexic). Large alpha motor neurons or 
their processes (peripheral nerves) also 
maintain normal muscle tone. With LMN 
injury, muscle wasting is usually severe and 
within 5–7 days of injury.
NervousSIGNALMENT
SIGNS
Limb weakness—acute or gradual onset.
• Owner may describe the patient as being 
“down,” unable to move, walk, or get up. 
• Many focal compressive spinal cord diseases 
begin with ataxia and progress to weakness, 
then to paralysis.
• Usually normal, unless the disease is 
systemic. • If in pain, patient may resent 
handling and manipulation. • Aortic emboli 
(ischemic neuromyopathy)—patient may be 
paraplegic and areflexic or hyporeflexic; 
femoral pulses absent; limbs often cold; nail 
beds often blue.
• Confirm that the problem is weakness or 
paralysis. • If limbs are paralyzed—likely 
bladder is also paralyzed, negating voluntary 
urination. • Localize problem to either LMN 
or UMN system. • Tetraparesis with 
exaggerated spinal reflexes in all limbs—lesion 
located at C1–C5 spinal segments or in the 
brain. • Tetraparesis with normal or 
depressed front limb spinal reflexes and 
exaggerated pelvic limb spinal reflexes—lesion 
located at C6–T2 spinal segments. 
• Tetraparesis with depressed spinal reflexes 
and decreased muscle tone in all limbs—
lesion is diffuse involving muscles or 
peripheral nerves, or both intumescences 
(cervical C6–T2 spinal cord segments and 
lumbar L4–S2 spinal segments). • Normal 
front limbs but paraparesis/paraplegia with 
located at T3–L3 spinal segments. • Normal 
depressed to absent pelvic limb spinal 
reflexes—lesion located at L4 spinal segment 
and caudally. • Normal front limb and pelvic 
limb motor activity but flaccid tail/anus and 
urinary and/or fecal incontinence—lesion 
located at S2 spinal segment and caudally. 
• Normal front limbs but paraparesis/
paraplegia and depressed patellar reflexes—
lesion involves spinal segments L4–6, located 
in vertebral bodies L3–4. • Normal front 
limbs but paraparesis/paraplegia, exaggerated 
patellar reflexes, and weak flexor and sciatic 
reflexes—if only the spinal cord is affected 
(no root involvement), lesion involves spinal 
segments L6–S2, located in vertebral bodies 
L4–L6.
CAUSES
Quadriplegia
• If LMN system—acute onset: acute idiopathic 
polyradiculoneuritis (coonhound paralysis), 
botulism, tick paralysis, fulminating form of myasthenia gravis, protozoal myoneuritis. • If 
LMN system—more gradual onset: 
polyneuropathies and polymyopathies from 
toxicity, infection, inflammation, endocrinopathy, 
metabolic disease, or congenital/inherited disease. 
• If UMN system—acute onset: disc herniation; 
fibrocartilaginous embolism; trauma; neoplasia; 
myelitis of many causes. • If UMN system—
gradual onset: disc herniation; discospondylitis; 
neoplasia; myelitis of many causes; malformations 
of the spine or spinal cord.
Paraplegia
• If UMN or LMN system—acute onset: disc 
herniation; fibrocartilaginous embolism; 
neoplasia; trauma. • If UMN or LMN 
system—gradual onset: disc herniation; 
congenital malformations of spine or spinal 
cord; degenerative myelopathy; lumbosacral 
instability; discospondylitis; neoplasia.
Quadriplegia with Cranial Nerve Deficits, 
Seizures, or Stupor
• UMN system—diseases of the brainstem: 
encephalitis; neoplasia; trauma; vascular 
accidents; congenital or inherited disorders.
• Degenerative disc disease—dachshunds, 
poodles, cocker spaniels, beagles, others. 
• Hunting dogs—acute idiopathic 
polyradiculoneuritis (coonhound paralysis). 
• Roaming animals—spinal cord and 
vertebral trauma, tick paralysis, botulism. 
• Atlantoaxial luxation—toy and small breeds. 
• Lumbosacral instability—large breeds, 
working breeds, German shepherd dogs. 
• Cervical spondylomyelopathy (wobbler 
syndrome)—large breeds, Doberman 
pinschers, Great Danes. • Syringomyelia—
cavalier King Charles spaniels, brachycephalic 
toy breeds and others. • Spinal arachnoid 
diverticulum: Rottweilers, pugs, small breeds.
  DIAGNOSIS
• Weak or paralyzed pelvic limbs—ensure 
femoral pulses are present and normal; aortic 
or femoral artery emboli may lead to LMN 
paraparesis or paraplegia. • Spinal reflexes—
localize weakness to the cervical, 
thoracolumbar, or lower lumbar cord 
segments. • Acute onset—be careful when 
moving patient if possibility of trauma.
Usually normal, unless inflammatory diseases 
involved.
• Urinary tract inflammation—urine culture 
may be positive in discospondylitis or in any 
dog that has had chronic bladder paralysis or 
repeated urinary catheterizations.

Canine and Feline, Seventh Edition  1041
P
• Discospondylitis—diagnose by spinal 
radiography (intervertebral disc space lysis); 
perform Brucella  titer; consider blood and urine 
bacterial cultures. • Exercise-induced 
weakness—determine acetylcholine receptor 
antibody titers (test for myasthenia gravis); 
check serum creatine kinase concentration 
(polymyositis or polymyopathy), red blood cell 
count (anemia or polycythemia), and blood 
glucose concentration (hypoglycemia); check 
for cardiac arrhythmia/hypoxia via 
electrocardiogram, thoracic radiography, Holter 
monitoring, echocardiography; muscle biopsy. 
• LMN weakness or muscle pain, muscle 
atrophy, or hypertrophy—determine creatine 
kinase concentration (polymyositis or 
polymyopathy); evaluate Neospora caninum  and 
Toxoplasma gondii  serum titers; perform 
electromyography, nerve conduction, muscle 
and nerve biopsies. • Myelitis or meningitis—
Dog: perform titers for N. caninum , T. gondii , 
canine distemper virus and/or fungal diseases; 
perform PCR for Rocky Mountain spotted 
fever, Ehrlichia  spp., and canine distemper 
virus; evaluate spinal fluid for infectious 
diseases. Cat: evaluate for feline leukemia virus 
and feline immunodeficiency virus; perform 
serum titers for T. gondii  and Cryptococcus  spp.; 
evaluate spinal fluid for signs of feline infectious 
peritonitis virus and Cryptococcus  spp.
IMAGING
• Spinal radiography—may reveal disc 
herniation, discospondylitis, bony tumor, 
congenital vertebral malformation, and 
fracture or luxation. • Myelography—
required if survey radiography not diagnostic 
and if CT or MRI unavailable. • CT or 
MRI—has replaced myelography where 
technology is available.
• CSF—before myelography to detect 
myelitis and meningitis; if high protein value 
or inflammatory cells, consider infectious 
disease diagnostics (titers, PCR). • Needle 
electromyography and motor nerve 
conduction velocity—may help with 
diagnosis and characterization of generalized 
LMN. • Muscle and nerve biopsy—
generalized LMN weakness. • Aspiration of 
intervertebral disc space under fluoroscopy if 
discospondylitis observed on imaging 
studies—perform cytology and culture to 
isolate an infectious agent.
  TREATMENT
• Inpatient—with severe weakness or paralysis 
until bladder function can be ascertained. • Hand feeding if necesssary—with diffuse 
LMN, swallowing can be affected. • Feeding 
from an elevated platform or installation of a 
feeding tube if necessary—recommended for 
animals with megaesophagus. • Activity—
restrict until spinal trauma and disc herniation 
can be ruled out. • Physical therapy—
important for paralyzed patients; tone muscles 
and keep joints flexible. • Bedding—check 
and clean frequently to prevent urine scalding 
and superficial pyoderma; use padded bedding 
or waterbed to help prevent decubital ulcer 
formation. • T urn quadriplegic patients from 
side to side 4–8 times daily to prevent 
hypostatic lung congestion and decubital ulcer 
formation. • Surgery—for disc herniation, 
fracture, and some neoplasias and congenital 
conditions; often the quickest and most 
effective method to improve neurologic status.
• Medications depend on underlying cause of 
weakness. • NSAIDs for spinal diseases 
associated with bone discomfort or pain. 
• Corticosteroid use, even in known diseases 
like spinal trauma or disc herniation, is 
controversial. May help to allay pain associated 
with some causes of paralysis, but does not 
expedite spinal cord recovery. • Dexamethasone 
0.1–0.2 mg/kg q48h for pain relief for 2–3 
doses. Prednisolone 0.5–1 mg/kg q12–24h for 
pain relief for 3–5 days. • Antibiotics or 
antifungals—used for discospondylitis, 
protozoal myelitis/meningitis. • Pyridostigmine 
bromide 0.5–3 mg/kg PO q8–12h for 
suspected myasthenia gravis; administer 
cautiously at low dose while waiting for titer 
results. • If acute generalized LMN signs—
check for ticks; use appropriate insecticides.
Corticosteroids—do not use with 
discospondylitis or fungal or protozoal myelitis/
meningitis; do not use with myasthenia gravis if 
aspiration pneumonia is present.
Corticosteroids—associated with GI ulceration 
and hemorrhage, delayed wound healing, and 
heightened susceptibility to infection.
• T ramadol 2 mg/kg q12h PO (dogs or cats), 
up to 4–5 mg/kg q12h (dogs only) for pain 
relief. Avoid using with antidepressants. 
• Gabapentin 3–10 mg/kg q12h PO  
for neuropathic pain. • Butorphanol 
0.2–0.6 mg/kg q2–4h for pain control.  FOLLOW-UP
• Neurologic examinations—daily to monitor 
status. • Bladder—evacuate (via manual 
expression or catheterization) 3–4 times a day 
to prevent overdistension and subsequent 
bladder atony; once bladder function has 
returned, patient can be managed at home.
• Urinary tract infection, bladder atony, urine 
scalding and pyoderma, constipation, decubital 
ulcer formation. • Aspiration pneumonia—
with generalized LMN disease or in any 
quadriplegic patient. • Myelomalacia—with 
severe spinal cord trauma or disc herniations. 
• Respiratory compromise or paralysis—with 
myelomalacia or generalized LMN disease.
SEE ALSO
Labrador Retrievers.
• Fibrocartilaginous Embolic Myelopathy.
• Intervertebral Disc Disease, Cervical.
• Lumbosacral Stenosis and Cauda Equine 
Syndrome.
• Myelopathy—Paresis/Paralysis—Cats.
• Neck and Back Pain.
• Pneumonia—Aspiration.
• Polyneuropathies (Peripheral Neuropathies).
• Schiff–Sherrington Phenomenon.
• Syringomyelia and Chiari-Like Malformation.
• LMN = lower motor neuron.
drug.
• UMN = upper motor neuron.
ed. St. Louis, MO: Elsevier-Saunders, 2015.
Negrin A, Schatzberg S, Platt SR. The 
paralyzed cat: neuroanatomic diagnosis and 
specific spinal cord diseases. J Feline Med 
Surg 2009, 11:361–372.
available online(continued)  Paralysis

1042  Blackwell’s Five-Minute Veterinary Consult  
PParaneoplastic Syndromes
  BASICS
Paraneoplastic syndromes (PNS) are a diverse 
group of systemic disorders resulting from the 
metabolic or physiologic effects of cancer on 
tissues remote from the tumor. These disorders 
are usually caused by production and release 
of substances not normally released by the 
cancerous cell of origin or in amounts not 
normally produced by those cells. Other 
etiologies of PNS aside from production of 
metabolically active substances include 
autoimmune disease stimulation, immune 
complex formation, immunosuppression, and 
ectopic receptor production/competitive 
blockade of normal signaling molecules.
The pathophysiology depends on the specific 
PNS (see Table 1). Many PNS in veterinary 
medicine have an unknown pathophysiologic 
etiology.
Any body system can be affected by a PNS. 
Some of the more common systems include:
• Endocrine/metabolic—hypercalcemia.
GENETICS
One known genetic cause of a PNS is the 
mutation H255R of the encoding folliculin gene 
(FLCN ) leading to renal cystadenocarcinoma 
and nodular dermatofibrosis, predominantly 
seen in German shepherd dogs but rarely noted 
in non-shepherds.
Any dog or cat with a histologically malignant 
(most common) or benign cancer (rare).
SIGNS
Vary with tumor type and organ systems 
affected but include:
• Alopecia (feline paraneoplastic syndrome).
• Anemia.
• Cutaneous flushing.
• Diencephalic syndrome.
• Gastroduodenal ulceration.
• Nodular dermatofibrosis.
• Thrombocytosis.CAUSES
By definition, PNS are caused by an under -
lying neoplasia, and occur due to a wide range 
of tumor-related factors including substances 
secreted from the tumor or cells within the 
local microenvironment. Many PNS do not 
have a recognized etiology.
  DIAGNOSIS
Varies with syndrome.
Helpful in identifying and monitoring several 
of the reported syndromes.
Ionized calcium and parathormone levels—assess 
patients with hypercalcemia; hypercalcemia of 
malignancy usually characterized by high ionized 
calcium and inappropriate parathormone (PTH) 
levels; may have elevated parathyroid hormone-
related protein (PTH-rP).
IMAGING
Imaging is crucial for the detection of many 
of the tumors that underlie the PNS:
• Radiography—assess thorax for masses, 
assess bones for lytic lesions, and detect 
hypertrophic osteopathy.
• Abdominal ultrasound—assess liver/spleen/
kidneys/pancreas/GI tract for masses
• Ventral neck ultrasound—assess for 
parathyroid or thyroid masses.
• Advanced imaging (CT or MRI)—more 
sensitive detection of occult tumors within 
body cavities.
• Fine-needle aspirate and cytology—can 
provide diagnosis for several tumor types 
commonly associated with PNS, including 
lymphoma, multiple myeloma, and apocrine 
gland adenocarcinoma of the anal sac.
• Biopsy—may be needed for some tumor 
types; also use to diagnose paraneoplastic skin 
lesions.
  TREATMENT
• Varies based on the underlying tumor and 
the clinical manifestations of the 
• The only definitive treatment is to address 
the underlying neoplasia rather than to try to 
control the clinical signs of the paraneoplastic 
syndrome. If the primary tumor cannot be 
treated, then management of clinical signs is 
indicated for palliation.  MEDICATIONS
Depends on underlying tumor type.
  FOLLOW-UP
As for underlying tumor type.
• AGASACA = apocrine gland 
adenocarcinoma of the anal sac.
• PNS = paraneoplastic syndromes.
• PTH = parathormone.
• PTH-rP = parathyroid hormone-related 
protein.
Garneau MS, Price LL, Withrow SJ, et al. 
Perioperative mortality and long-term 
survival in 80 dogs and 32 cats undergoing 
excision of thymic epithelial tumors. Vet 
Surg 2015; 44:557–564
Lucas P , Lacoste H, de Lorimier LP , Fan TM. 
T reating paraneoplastic hypercalcemia in 
dogs and cats. Vet Med May 1, 2007.
Sternberg RA, Wypij J, Barger AM. An 
overview of multiple myeloma in dogs and 
cats. Vet Med Oct 1, 2009.
T umielewicz KL, Hudak D, Kim J, et al. 
Review of oncological emergencies in small 
animal patients. Vet Med Sci 2019, 
5(3):271–296.
T urek MM. Cutaneous paraneoplastic 
syndromes in dogs and cats: a review of the 
literature. Vet Dermatol 2003, 14:279–296.

Canine and Feline, Seventh Edition  1043
P
Table 1
SyndromePrimary Tumor Association 
(Dog)Primary Tumor 
Association (Cat) Primary Mechanism
Alopecia Adrenal carcinoma Dogs: due to an excess of cortisol production; 
most often associated with 
hyperadrenocorticism
Alopecia (feline 
paraneoplastic alopecia)Pancreatic carcinoma 
and carcinoma of 
the biliary treeCats: mechanism unknown. See Adenocarcinoma, 
Pancreas; Feline Paraneoplastic Alopecia; 
Hyperadrenocorticism (Cushing’s 
Syndrome—Cats)
Cutaneous flushing 
syndromePheochromocytoma; mast cell 
tumorNot reported Inappropriate release of vasoactive substances, 
such as histamine, causes paroxysmal flushing 
of the skin
Diencephalic syndrome Astrocytoma, anaplastic 
ependymomaNot reported Tumor is present in the diencephalon region of 
the brain; excess of growth hormone results in 
dramatic weight loss (without acromegaly) 
despite adequate caloric intake
Disseminated intravascular 
coagulationHemangiosarcoma; many 
othersMyeloproliferative 
diseaseSee Disseminated Intravascular Coagulation
Eosinophilia Assorted, including 
lymphoma and mast cell 
tumorsAssorted, including 
lymphoma and 
mast cell tumorsMay be due to stimulation of eosinophil 
precursors by products such as interleukin-2, 
-3, and -5 and granulocyte–macrophage 
colony-stimulating factor
Exfoliative dermatitis (feline 
thymoma-associated 
exfoliative dermatitis)Not reported Thymoma Not completely elucidated, likely due to the 
induction of autoreacting T-lymphocytes
Feminization syndrome Testicular tumors—especially 
functional Sertoli cell and 
seminoma tumorsNot reported Due to hyperestrogenism or a relative 
testosterone:estrotgen imbalance that is 
uncomplicated by myelosuppression
Gastroduodenal ulceration Non-islet cell pancreatic 
neoplasia; mast cell tumorRare Inappropriate gastrin secretion (non-islet cell 
tumor) or excess histamine secretion (mast cell 
tumor)
Hypercalcemia Lymphoma; apocrine gland 
adenocarcinoma of the 
anal sac (AGASACA); 
multiple myeloma; othersRelatively rare; 
lymphoma; 
squamous cell 
carcinoma; othersDogs: multiple secreted factors involved; 
AGASACA is the most likely tumor to lead to 
parathyroid hormone-related protein (PTHrP) 
production Cats: mechanisms unexplored. See 
Hypertrophic osteopathy Metastatic and primary 
tumors of the lung, also 
seen with intra-abdominal 
tumorsMetastatic and 
primary tumors of 
the lung, also seen 
with intra-
abdominal tumorsCharacterized by severe lameness and distal limb 
soft tissue swelling followed by periosteal new 
bone growth. The etiology is unknown. Several 
mechanisms likely play a role, including vagally 
mediated changes in limb perfusion, cytokine 
and growth factor secretion, immune 
mechanisms, vascular thrombi caused by 
platelets and antiphospholipid antibodies, and 
interaction between activated platelets and the 
endothelium
Hyperviscosity syndrome Immunoglobulin-secreting 
tumor (e.g., multiple 
myeloma, lymphoma, and 
rarely plasma cell tumor)Immunoglobulin-
secreting tumorAccumulation of large immunoglobulin proteins 
or polymerized small immunoglobulin proteins 
in the blood that result in decreased blood 
flow from increased viscosity. See Multiple 
Myeloma and Paraproteinemia(continued)  Paraneoplastic Syndromes

1044  Blackwell’s Five-Minute Veterinary Consult  
PSyndromePrimary Tumor Association 
Hypoglycemia Insulinoma; benign and 
malignant smooth muscle 
tumors; large mesenchymal 
tumors; othersRare; insulinoma Involves the excess production of insulin or 
insulin-like factors or excessive glucose 
utilization. See Insulinoma
Immune complex disorders Lymphocytic leukemia; 
primary erythrocytosisLymphoma Secondary to antigen-antibody–immune complex 
activation; glomerulonephritis is most 
recognized problem
Myasthenia gravis Thymoma; others Very rare; thymoma Exact mechanism is unknown, likely immune-
mediated, may be due to effects of follicular 
helper T-cells. See Myasthenia Gravis
Myelofibrosis Assorted Assorted See Myelodysplastic Syndromes
Neutrophilic leukocytosis Hemangiosarcoma; 
lymphoma; othersAssorted; lymphoma, 
carcinomas and 
sarcomasProduction of a granulocyte–monocyte-
stimulating cytokine is likely cause
Nodular dermatofibrosis Renal cystadenoma or 
cystadenocarcinoma 
primarily in German 
shepherd dogs and 
shepherd crossesNot reported Mechanism is unknown but involves proliferation 
of fibroblasts. Propensity to develop is 
inherited in an autosomal dominant pattern. 
May be linked to chromosome 5. Loss of 
heterozygosity/function of the FLCN  gene may 
contribute to neoplastic transformation of 
renal epithelial cells. Renal tumors are usually 
slowly progressive and almost always bilateral
Pemphigus Rare; reported in one case of 
mediastinal lymphoma and 
one splenic sarcomaNot reported Autoimmunity to target antigens (periplakin and 
envoplakin) in the skin
Peripheral nerve syndromes Various Not reported Unknown, but usually subclinical and secondary 
to changes in myelination
Polycythemia Renal sarcoma and 
carcinoma; othersRenal carcinoma Inappropriate secretion of erythropoietin or 
erythropoietin-like peptides. See Polycythemia 
Vera
Superficial necrolytic 
dermatitis (metabolic 
epidermal necrosis, 
hepatocutaneous 
syndrome, necrolytic 
migratory erythema)Hepatic neoplasia; pancreatic 
neoplasia (glucagonoma)Pancreatic neoplasia 
(glucagonoma)Many names used to describe similar clinical 
entities; usually observed in patients with 
hepatic disease and less commonly with 
glucagon-secreting pancreatic tumors; 
sometimes referred to as glucagonoma 
syndrome; exact mechanism is unclear; may 
see associated glucose intolerance or diabetes 
mellitus
Thrombocytopathy Immunoglobulin-secreting 
tumorsImmunoglobulin-
secreting tumorsImmunoglobulin molecules inhibit normal platelet 
aggregation. See Thrombocytopathies
Thrombocytopenia Lymphoma, multiple 
myeloma, 
hemangiosarcoma, othersLymphoma, others Thrombocytopenia, primary immune-mediated or 
secondary to myelophthisis. See 
Thrombocytopenia and Thrombocytopenia, 
Primary Immune-Mediated
Thrombocytosis Myeloproliferative disorders Myeloproliferative 
disordersOverproduction of cytokines that stimulate 
thrombopoietin production (e.g., interleukin-1, 
-3, -6, -11)Paraneoplastic Syndromes  (continued)
Table 1
(Continued )

Canine and Feline, Seventh Edition  1045
P
Paraphimosis, Phimosis, and Priapism
  BASICS
OVERVIEW
• Phimosis—inability to protrude the penis 
beyond the preputial orifice.
• Paraphimosis—inability for exteriorized 
penis to retract into the sheath.
• Priapism—prolonged extrusion of an erect 
penis not associated with sexual arousal.
• German shepherd dog, Golden retriever 
(phimosis)—observed congenital preputial 
stenosis; possibly hereditary.
• Siamese cat—overrepresented.
SIGNS
• Phimosis—can go undetected until 
unsuccessful copulation attempts as an adult; 
severe cases in the neonate resulting in 
preputial urine pooling may lead to 
balanoposthitis and septicemia.
• Paraphimosis—initially: licking of an 
exteriorized penis; after hours of exposure: 
ischemic necrosis and urethral obstruction; 
edema and swelling may make differentiation 
from priapism difficult.
• Priapism—persistent penile erection lasting 
>4 hours; bulbus glandis firm and swollen.
• Phimosis—abnormally small preputial 
orifice; congenital or acquired (e.g., caused by 
injury or disease); may be associated with 
persistent penile or preputial frenulum (thin 
band of connective tissue joining the penis 
and prepuce along the ventral glans).
• Paraphimosis—preputial hair rings; stenotic 
preputial orifice; injury; os penis fractures; 
neurologic disease (encephalomyelitis, 
intervertebral disc disease); penile swelling 
(neoplasia, balanoposthitis, strangulation with 
foreign body); incompetent preputial muscles.
• Priapism—ischemic (most common and 
serious in nature, veno-occlusive/low flow): 
cause often unknown, trauma during mating, 
chronic distemper encephalomyelitis, penile 
thromboembolism, amphetamine use, penile 
neoplasia, perineal abscess; nonischemic 
(arterial/high flow): trauma, vasoactive drugs, 
neurologic conditions, canine distemper; less 
likely to cause necrosis due to lack of venous 
  DIAGNOSIS
• Phimosis (cats)—inability for penis to 
exteriorize in prepubertal tom cats is normal as penile adhesion breakdown is androgen-
dependent and occurs about 7–12 months of 
age; early neutered cats may continue to 
maintain penile adhesion.
• Paraphimosis—abnormality of the retractor 
penis muscles or prepuce muscles, large 
preputial opening, short prepuce, or priapism.
• Priapism—urethral obstruction.
• Phimosis in neonates—septicemia may 
result from preputial urine pooling.
Penile blood-gas analysis differentiates forms 
of priapism:
◦ Ischemic (i.e., veno-occlusive)—pH 
<7.25, P o2 <30 mmHg, P co2 >60 mmHg; 
may respond to phenylephrine therapy (see 
◦ Nonischemic (i.e., arterial)—pH of 7.4, 
Po2 >90 mmHg, P co2 <40 mmHg.
• Ultrasonography—visualization of 
engorged penile vessels.
• Neurologic exam, radiographs, magnetic 
resonance imaging—to evaluate spinal cord.
  TREATMENT
Phimosis
• Surgical enlargement of the preputial orifice, 
if required, due to presenting clinical signs.
• Persistent penile frenulum (dogs)—remove 
band of tissue holding the glans penis to the 
parietal lamina of prepuce.
Paraphimosis and Priapism
• Main goal—detumesce (priapism) and 
replace the penis within the prepuce.
• Castration not effective; not testosterone- 
• At times only lubrication required 
(paraphimosis).
• Penile amputation and urethrostomy 
required if excessive damage present.
• If urethral patency is in question place an 
indwelling urinary catheter.
• Under sedation, apply firm pressure wrap 
soaked with hypertonic glucose solution 
(decrease edema), firmly replace within prepuce 
once able; temporary preputial stay sutures may 
be required for continued reduction (preputial 
orifice patency for urine flow required if urinary 
catheter not maintained); surgically enlarge 
preputial orifice, if necessary.
• Recurrent paraphimosis may require 
phallopexy.
• Aspiration of penile blood may provide 
analgesia and prove diagnostic (blood gas 
analysis).• Intrapenile phenylephrine may enhance 
venous outflow if veno-occlusive priapism.
• Penile amputation and perineal urethros-
tomy—indicated for cats with difficulty 
urinating.
• Antibiotic ointments—prevent penile 
adhesions with prepuce.
• Phenylephrine (priapism)—intracavernosal 
infusion of 100–500  μg diluted in 1 mL of 
0.9% saline.
  FOLLOW-UP
• Phimosis—fair to good if identified prior to 
development of septicemia.
• Paraphimosis and priapism—depending on 
cause, may be guarded to poor for return to 
breeding activity; fair to good for life with 
successful medical and/or surgical 
Disorders of the feline penis and prepuce. 
In: Canine and Feline Theriogenology. 
539–543.
Lavely JA. Priapism in dogs. Top Companion 
Anim Med 2009, 24:49–54.
acknowledge the prior contribution of Carlos 
R.F . Pinto.

1046  Blackwell’s Five-Minute Veterinary Consult  
PParaproteinemia
  BASICS
OVERVIEW
• The presence of excessive serum 
paraproteins. Paraproteins are produced by a 
single clone of cells and may be whole 
immunoglobulins, subunits, light chains, or 
heavy chains. Commonly seen with plasma 
cell neoplasms (multiple myeloma), chronic 
lymphocytic leukemia, or B-cell lymphoma. 
• Primary signs are related to the underlying 
neoplasm and could be related to bone or 
bone marrow invasion with neoplastic cells. 
• Markedly elevated paraprotein 
concentration can result in hyperviscosity 
syndrome (HVS).
• Musculoskeletal—bone lysis by neoplasia 
can cause pain, lameness and pathologic 
fractures. More common in dogs. 
• Nervous—vertebral lysis and HVS can cause 
neurologic abnormalities including seizures, 
acute blindness, paraparesis. • Hemic/
lymphatic/immune—myelophthisis and 
secondary immune-mediated destruction may 
cause cytopenias. Paraproteins may interfere 
with platelet and coagulation factor function; 
decreased production of normal immuno -
globulins may increase susceptibility to 
infection. • Ophthalmic—dilated, tortuous 
retinal vessels, retinal detachment, or retinal 
hemorrhage from HVS. • Cardiovascular—
HVS can cause hypervolemia and tachycardia, 
gallop rhythm, and cardiac failure (cats more 
than dogs). • Renal—failure due to antibody 
deposition in tubules.
• Dogs—middle to old aged. • Cats (rare)— 
middle to old aged. • No sex predilection.
SIGNS
• Lethargy and weakness. • Lameness, 
paresis. • Bleeding. • Blindness or retinal 
hemorrhage. • Polyuria and polydipsia. 
• Multiple myeloma—genetic predisposition, 
viral infections, chronic immune stimulation, 
and carcinogen exposure. • Lymphoma or 
leukemia linked to retroviral infections in cats.
  DIAGNOSIS
• Monoclonal gammopathy—extramedullary 
plasmacytoma, lymphoma, lymphocytic 
leukemia, ehrlichiosis, leishmaniasis, 
bartonellosis, dirofilariasis, plasmacytic gastroenteritis, feline stomatitis, feline 
infectious peritonitis (FIP). • Polyclonal 
gammopathy—chronic infectious/
inflammatory disorders, stomatitis, chronic 
autoimmune disease, and neoplasia. 
• Bleeding— thrombocytopenia, thrombo -
cytopathy, other coagulopathy. • Neurologic 
or ophthalmologic signs of HVS—intracranial 
or spinal disease (neoplasia, meningitis, 
immune-mediated), hypertension.
• Anemia/leukopenia/thrombocytopenia—
secondary to myelophthisis or autoimmune 
mechanisms; marked lymphocytosis 
associated with chronic lymphocytic leukemia 
or lymphoma. • Serum total protein and 
globulin concentrations—elevated. • Serum 
albumin concentration—may be low. 
• Serum total or ionized calcium concentra-
tion—elevated secondary to malignancy, renal 
failure, or bone lysis. • Proteinuria—caused 
by light chains (i.e., Bence Jones protein) not 
detected on routine urinalysis; urine protein 
electrophoresis to identify.
• Serum/urine protein electrophoresis—to 
further characterize immunoglobulins. 
• Immunoelectrophoresis—helps define the 
type of gammopathy. • Infectious disease 
testing (serology or PCR as indicated). • Flow 
cytometry—characterization of leukemia, 
lymphoma.
IMAGING
• Skeletal survey radiographs or bone 
scan—identify lytic lesions and sites to 
aspirate or biopsy. Common locations for 
multiple myeloma lesions include vertebral 
bodies, ribs, pelvis, skull, and proximal long 
bones. • Thoracic and abdominal radiographs 
or ultrasound.
• Bone marrow aspiration/biopsy—
plasmacytosis is often marked (>20%) in 
dogs with multiple myeloma (<5% is 
normal); in cats, presence of plasma cell 
atypia is more important than number. 
• Biopsy of lytic bony lesions. • Organ or 
lymph node aspiration—to identify 
neoplastic populations of cells, Leishmania  
amastigotes, or amyloid. Relatively 
contraindicated with coagulopathy.
  TREATMENT
• Supportive care—analgesia, anticonvulsant 
therapy, other therapy as indicated. 
• Automated or manual plasmapheresis may 
rapidly decrease paraproteins. 
• Chemotherapy for neoplasia.  MEDICATIONS
See specific diseases.
  FOLLOW-UP
• See specific diseases. • Electrophoresis may 
be monitored to assess response to therapy.
SYNONYMS
• Monoclonal gammopathy. • M protein.
SEE ALSO
• FIP = feline infectious peritonitis. 
• HVS = hyperviscosity syndrome.
Boyle TE, Holowaychuk MK, Adams AK, 
Marks SL. T reatment of three cats with 
hyperviscosity syndrome and congestive 
heart failure using plasmapheresis. J Am 
Anim Hosp Assoc 2011, 47:50–55.
Francey T, Schweighauser A. Membrane-
based therapeutic plasma exchange in dogs. 
J Vet Intern Med 2019, 33(4):1635–1645.
hyperglobulinemia: diagnosis and therapy. 
In: Bonagura JD, Kirk RW, eds., Kirk’s 
Current VeterinaryTherapy XII. 
Philadelphia, PA: Saunders, 1995, pp. 
523–530.
Author  Kristina Meichner
acknowledge the prior contribution of Julie 
Armstrong.

Canine and Feline, Seventh Edition  1047
PPatellar Luxation
  BASICS
Medial or lateral displacement of the patella 
from its normal anatomic position in the 
femoral trochlea.
• Clinical signs may be mild to severe; 
different degrees of clinical and pathologic 
changes; classified into grades I–IV (see 
Physical Examination Findings). • Common 
musculoskeletal changes occur secondary to 
abnormal forces on the femur and tibia and 
lack of normal patellar position during 
growth—tibial rotation on its long axis; 
bowing of the distal femur and proximal 
tibia; shallow to absent femoral trochlea; 
dysplasia of the femoral and tibial epiphysis; 
displacement of the quadriceps muscle 
group.
GENETICS
• Recessive, polygenic, and multifocal 
inheritances proposed. Genetic markers are 
not yet identified to facilitate the choice of 
selective elimination of patella luxation from 
specific breeds. • Hereditary factor in Devon 
Rex cats.
• One of the most common stifle joint 
abnormalities in dogs. • Medial—>75% of 
cases (large and small dogs and cats). 
• Bilateral involvement—50% of cases. 
• Uncommon in cats, but may be more 
common than suspected because most 
affected cats are not lame.
Species
• Rarely cat.
• Most common in toy and miniature dog 
breeds. • Dogs—miniature and toy poodles; 
Yorkshire terriers; Pomeranians; Pekingese; 
Chihuahuas; Boston terriers. In large-breed 
dogs, Great Pyrenees and Labrador retrievers 
are most commonly affected.
Clinical signs—may develop soon after 
birth with severe luxation or secondary 
bone deformities; generally after 4 months 
of age. Mild clinical signs that are not 
interpreted by clients as lameness are often 
undetected until secondary osteoarthritis 
advances.
Risk for females 1.5 times that for males.SIGNS
Clinical expression depends on grade (severity), 
amount of degenerative arthritis, chronicity of 
disease, and occurrence of other stifle joint 
abnormalities (e.g., cruciate ligament rupture).
• Persistent abnormal hind limb carriage and 
function in neonates and puppies. Clients 
may complain of “bowed legs” (genu varum) 
or crouched gait in small-breed dogs. 
• Occasional skipping or intermittent hind 
limb lameness—worsens in young to mature 
dogs. • Sudden signs of lameness—owing to 
minor trauma or worsening degenerative joint 
disease in mature animals.
• Grade I—patella can be manually displaced 
from the trochlea, but immediately resumes a 
normal position when pressure is released. 
Usually an incidental finding on physical 
examination and is not normally associated 
with clinical lameness. • Grade II—patella can 
be manually displaced or can spontaneously do 
so with flexion of the stifle joint; patella 
remains malpositioned until it is manually 
reduced or the patient extends the stifle joint. 
Patient intermittently carries the affected limb 
with the stifle joint flexed, but ambulates 
normally at other times. • Grade III—patella 
remains luxated most of the time but can be 
manually reduced with the stifle joint in 
extension; movement of the stifle joint results 
in reluxation of the patella. • Grade IV—
patella is permanently luxated and cannot be 
manually repositioned; may be up to 90° of 
rotation of the proximal tibial plateau; shallow 
or missing femoral trochlea. • Grades III and 
IV—crouching, bowlegged (genu varum) or 
knock-kneed (genu valgum) stance for medial 
or lateral luxations, respectively; more of the 
body weight is transferred to the front limbs. 
• Pain—occurs as the patella relocates or if 
abrasion creates contact with exposed bone.
CAUSES
• Congenital due to polygenetic influences. 
• Rarely, traumatic; clinical history will 
determine traumatic etiology and secondary 
bone malformations are not present in acute 
traumatic patella luxation.
Coxa vara—lateral displacement of the 
proximal femur; vastus medialis and rectus 
femoris muscles pull the patella medially.
  DIAGNOSIS
• Cranial cruciate ligament rupture—positive 
cranial drawer; concurrent in 15–20% of cases. • Avulsion of the tibial tubercle—
patellar alta. • Rupture of the patellar 
tendon—patella alta. • Excessive tibial 
plateau angle—patella baja. • Malunion and 
malalignment of fractures of the femur or 
tibia—may result in displacement of the 
quadriceps muscle group.
Not useful in the diagnosis of patella luxation 
in the dog.
 IMAGING
Patella luxation is diagnosed based on clinical 
signs and physical examination. CT or 
orthogonal radiography of the femur and 
tibia may be indicated in grade III and IV 
luxations to assess bowing and torsion of the 
femur and tibia and evaluate the need for 
femoral or tibial osteotomy as an adjunct to 
• Palpation of patellar position and 
movement during flexion and extension of 
the stifle. Medial and lateral force exerted on 
patella to relocate the patella into the 
trochlear groove (if luxated) or luxate the 
patella (in grade I or II luxations). 
• Calculation of the “Q-angle,” or the angle 
of the direction of the quadriceps femoris 
muscle, under MRI may help to differentiate 
patella luxation from dogs with partial cranial 
cruciate ligament rupture. Q-angle (10.5° in 
normal dogs) increases with increasing grade 
of patella luxation, but should be only slightly 
increased in dogs with cranial cruciate 
rupture.
• Gross—cartilage wear lesions of the patella 
and femoral trochlea; joint capsule 
redundancy on the side opposite to luxation; 
fibrosis and contracture on the side of 
luxation. • Microscopic—cartilage fibrillation 
and loss of glycosaminoglycan content; 
  TREATMENT
• Outpatient—all grade I and some grade II 
luxations. • Inpatient (surgery)—most grade 
II and all grade III and IV luxations.
• Cryotherapy (ice packing)—immediately 
after surgery; 5–10 minutes q8h for 3–5 days, 
followed by warm-packing, 5–10 minutes 
q8h for 3–5 additional days. • Passive stifle 
range-of-motion exercises—as soon as 
ACTIVITY
Normal to restricted, depending on severity 
and if surgical correction was performed.

1048  Blackwell’s Five-Minute Veterinary Consult  
PDIET
Weight control—decreases the load and stress 
on the patella support mechanism.
• Discuss the heritability of the condition. 
• Warn about relapse potential after surgery. 
Retrospective studies indicate that 8–19.8% of 
patellas reluxate after surgery. Revision surgery is 
necessary in 13% of cases. • Inform about 
increased risk of cranial cruciate ligament 
disease. • Warn that the condition could worsen 
over time (e.g., from grade I to grade II).
• Malalignment is the underlying cause—
tibial crest transposition is the definitive 
realignment procedure, but often needs to be 
combined with other techniques such as 
sulcoplasty. • Retinacular and joint capsule 
tension on the side of luxation prevents 
realignment—medial capsulotomy (release) is 
essential. • Shallowness of the trochlea sulcus 
is assessed and managed with one of the 
following: ◦ T rochleoplasty—rasp or burr to 
deepen the sulcus. Not recommended as a 
primary means of deepening the sulcus 
because of the poor quality of the fibro -
cartilage upon healing; often leads to 
increased secondary osteoarthritis of the stifle. 
◦ T rochlea chondroplasty—only indicated in 
very young dogs because of easy separation of 
the cartilage and subchondral bone in these 
dogs; lift the surface hyaline cartilage and 
curette out cancellous bone to deepen the 
sulcus; lay the cartilage back over exposed 
bone. ◦ Recession sulcoplasty—remove a 
pie-shaped wedge; deepen the defect, replace 
the wedge; preferred technique for most 
patients since the surface cartilage is mostly 
intact. ◦ Block recession sulcoplasty—remove 
a block instead of a wedge; increases surface 
area of cartilage in contact with patella. More 
difficult surgical procedure than simple 
recession sulcoplasty. ◦ T ransposition of the 
tibial tubercle—realign the longitudinal axis 
of the quadriceps mechanism so that it is 
centered over the femoral trochlea, in effect, 
deepening the Q-angle; osteotomize the tibia 
tubercle leaving it attached distally, transpose 
it opposite the direction of luxation, and 
stabilize it with K-wires and, in larger dogs, a 
tension band wire. ◦ Imbricate the joint 
capsule and supporting soft tissues on the side 
opposite the luxation—to help keep the 
patella in the sulcus. Imbrication can occur by 
removal of a longitudinal full-thickness 
portion of the excess capsule and edge-to-edge 
tissue apposition during closure (strongest 
method), or by overlapping the joint capsule 
incision with a “vest-over-pants” surgical 
technique. Imbrication as a sole procedure is 
not sufficient to permanently correct the 
position. ◦ Corrective osteotomies of the distal femur and proximal tibia—realigns the 
longitudinal axis of the hind limb; generally 
indicated most commonly for grade IV 
luxations with significant femoral or tibial 
bowing and torsion.
(NSAIDs)—minimize pain; decrease 
inflammation; meloxicam (load 0.2 mg/kg 
PO, then 0.1 mg/kg q24h PO—liquid), 
carprofen (2.2 mg/kg PO q12h), etodolac 
(10–15 mg/kg PO q24h), deracoxib 
(3–4 mg/kg PO q24h—chewable) for 7 days 
(for postoperative pain). • Food supplement -
ation with omega-3 fatty acids to decrease 
inflammation and progression of secondary 
osteoarthritis. Commercial diets containing 
1.7–3.4% omega-3 fatty acids or precursors 
are beneficial.
Avoid corticosteroids because of potential side 
preclude their use.
damage and degeneration, but recent 
evidence suggests they are not or are only 
  FOLLOW-UP
• Post-trochleoplasty—encourage early, active 
use of the limb. Small-breed dogs are 
commonly reluctant to bear weight on the 
operated limb at an early period and are 
prime candidates for joint range of motion 
and other exercises to encourage early limb 
use. • Leash walk exercise for 4–8 weeks; 
prevent jumping. The duration of exercise 
restriction is variable depending on the 
surgical procedure with 4 weeks for only soft 
tissue corrections and 8 weeks for osteotomy 
procedures recommended. When corrected 
with tibial crest transposition, cage rest is 
indicated until follow-up radiographs indicate 
the crest is healed in its new position. • Yearly 
examinations—to assess progression of 
uncorrected patella luxation or to monitor 
progression of secondary osteoarthritis.PREVENTION/AVOIDANCE
Infection, recurrence, tibial crest avulsion, pin 
• With surgical treatment— >90% of patients 
are free from lameness and clinical dysfunction. 
• Osteoarthritis—radiographic evidence in 
almost all affected stifle joints after surgery. 
Clinical impact appears minimal in small dogs.
Cranial cruciate ligament rupture.
SEE ALSO
Arthritis (Osteoarthritis).
drug.
Arthurs GI, Langley-Hobbs SJ. Complications 
associated with corrective surgery for 
patellar luxation in 109 dogs. Vet Surg 
2006, 34:559–566.
Kowaleski MP , Boudrieau RJ, Pozzi A. Stifle 
joint. In: Johnston SA, Tobias KM, eds., 
Veterinary Srugery Small Animal, 2nd ed. 
St. Louis, MO: Elsevier, 2018, pp. 
1141–1159.
Linney WR, Hammer DL, Shott S. Surgical 
treatment of medial patellar luxation 
without femoral trochlear groove deepening 
procedures in dogs: 91 cases (1998–2009). J 
Am Vet Med Assoc 2011, 238:1168–1172.
Roush JK. Canine patellar luxation. Vet Clin 
North Am 1993, 23:855–875.
Schultz KS. Diseases of the joints. In: Fossum 
TW, ed., Small Animal Surgery, 4th ed. St. 
Louis, MO: Elsevier Mosby, 2013, pp. 
1353–1362.
Towle HA, Griffon DJ, Thomas MW, et al. 
Pre- and postoperative radiographic and 
computed tomographic evaluation of dogs 
with medial patellar luxation. Vet Surg 
2005, 34(3):265–272.
available onlinePatellar Luxation  (continued)

Canine and Feline, Seventh Edition  1049
PPatent Ductus Arteriosus
  BASICS
Persistent patency of this normal fetal 
Due to insufficient vascular smooth muscle 
the ductus arteriosus fails to close after birth, 
maintaining a persistent communication 
between the low-pressure pulmonary artery 
(PA) and high-pressure aorta (see Web 
Figures 1 and 2). Blood typically shunts left 
to right, with hemodynamic consequences 
depending on the magnitude of the shunt, 
pulmonary vascular resistance, and 
concurrent heart defects. Moderate-to-large 
shunts cause left-sided congestive heart 
failure (CHF) from volume overload of the 
left ventricle (LV). Less often a large-
diameter patent ductus arteriosus (PDA) 
induces severe pulmonary vascular injury, 
high pulmonary vascular resistance, and 
pulmonary hypertension (PH), causing 
shunt reversal from Eisenmenger’s 
pathophysiology. This is termed a “reversed” 
PDA (rPDA), and leads to bidirectional 
shunting, arterial desaturation, and 
secondary erythrocytosis.
• Cardiovascular—volume overload or 
pulmonary vascular disease. • Hemic/lymph/
immune—potential for erythrocytosis and 
hyperviscosity. • Respiratory—cough or 
labored breathing from pulmonary edema or 
PH.
GENETICS
“Polygenic” model defect in many canine 
breeds.
Estimated prevalence up to 2.5 cases/1,000 
live canine births; less common in cats.
Species
Bichon frise, cavalier King Charles spaniel, 
Chihuahua, cocker spaniel, collie, English 
springer spaniel, German shepherd dog, 
Labrador retriever, Maltese, miniature (and 
toy) poodle, Pomeranian, Shetland sheepdog, 
and others.
• Vast majority identified during initial 
vaccination sequence. • Onset of signs—
Dogs—females predisposed in some breeds.SIGNS
• Signs vary by major hemodynamic effect at 
time of presentation—no signs vs. volume 
overload vs. increased pulmonary vascular 
resistance. • Onset of rPDA may be sudden 
in dogs (usually before 4–6 months of age); 
can develop gradually in cats but often before 
1 year of age. • Signs related to rPDA can be 
overlooked for years.
• Most have no clinical signs at initial 
evaluation. • Dyspnea, coughing, exercise 
intolerance with development of CHF . 
• Stunted growth in some. • Exertional rear 
limb weakness and complications of hyper -
viscosity (seizures or sudden death) with 
rPDA. • Signs usually precipitated by or 
worsened with exercise.
• Continuous, loud, machinery-type murmur 
loudest over PA at the left craniodorsal 
cardiac base; often a systolic mitral 
regurgitant murmur at the left apex. The 
murmur in puppies <6 weeks of age or cats of 
any age might resemble a long systolic and 
abbreviated diastolic murmur. • Precordial 
thrill. • Arterial pulses—hyperkinetic 
(“waterhammer”). • Caudoventral 
displacement of palpable LV apex. 
• Tachypnea, dyspnea, and inspiratory 
crackles—can indicate left-sided CHF or 
concurrent respiratory disease such as 
pneumonia. • Rapid, irregular cardiac 
rhythm with variable-intensity arterial pulses 
if atrial fibrillation develops—more common 
in large-breed dogs. • In rPDA findings 
differ— systolic ejection murmur with 
tympanic or split second heart sound; normal 
arterial pulses, prominent right ventricular 
impulse, and prominent jugular pulse. 
Differential cyanosis—blue discoloration 
limited to the caudal mucous membranes.
CAUSES
Genetic in most cases.
Breed and sex in dogs; unknown for cats.
  DIAGNOSIS
• Congenital aortic stenosis with aortic 
insufficiency (to-and-fro systolic/diastolic 
murmurs) and ventricular septal defect 
(VSD) with aortic valve prolapse (systolic 
murmur of VSD and diastolic murmur of 
aortic insufficiency). • Rare causes of 
continuous thoracic murmurs—pulmonary 
arteriovenous malformations, aortopulmonary communication, rupture of the aorta into the 
right atrium or ventricle, and coronary artery 
fistula. • Systemic arterial to PA vascular 
malformations can result in similar imaging 
findings to those of PDA but murmurs are 
often soft or absent. • Exertional rear limb 
weakness of rPDA often misdiagnosed as 
Usually normal unless rPDA (erythrocytosis 
with packed cell volume [PCV] 55–80%).
Low femoral arterial PO2 compared to 
brachial artery in rPDA (rarely necessary).
IMAGING
• Lateral projection—left cardiomegaly; 
pulmonary overcirculation; frequently the lobar 
pulmonary veins are slightly larger than 
attendant arteries (see Web Figure 3). 
• Dorsoventral projection—cardiac elongation 
(LV enlargement), left auricular enlargement, 
dilation of the descending aorta (“ductus 
bump”) and the main PA. • Left-sided 
CHF—distended pulmonary veins; increased 
interstitial/alveolar densities. • With rPDA—
heart normal sized but contour of the right 
ventricle (RV) is more prominent, the 
pulmonary circulation appears normal to 
reduced, and main PA and proximal lobar 
branches are dilated (see Web Figure 4); a ductus 
bump may be evident; lung fields are clear.
• The left atrium (LA), LV, ascending aorta, 
and main PA are dilated and LV systolic 
dysfunction might be observed. The RV is 
normal, except in rPDA or in some animals 
with progressive PH. • Ductal ampulla and 
the entry to PA can be imaged; optimally 
with transesophageal echo (see Web Figure 5). 
• Doppler studies demonstrate continuous 
flow into the main PA (see Web Figure 6), 
usually with concurrent pulmonary 
insufficiency from dilation of that vessel, 
along with mitral regurgitation from LV and 
LA dilation. T ransmitral flow velocity is 
increased from increased flow volume and LA 
pressure. Aortic outflow velocities are 
augmented substantially (often around 
3 m/s), mimicking mild aortic stenosis. T race 
aortic regurgitation is common from aortic 
dilation. • With rPDA—small left heart 
chambers, right atrial dilation, RV hyper -
trophy, and dilation of the main PA and 
branches. Saline contrast injected in 
peripheral vein is identified in the abdominal 
aorta. Color and spectral Doppler studies 
identify low velocity and bidirectional or 
right-to-left shunting across ductus (see Web 
Figure 7). High-velocity pulmonary and 
tricuspid regurgitation indicate PH.

1050  Blackwell’s Five-Minute Veterinary Consult  
PAngiography
Fluoroscopic angiography or CT angiography 
can be useful for the differential diagnosis of 
rare aortic or coronary arterial malformations, 
abnormal aortic arch (with right-sided PDA), 
systemic to pulmonary arterial malformations, 
and during interventional catheterization 
procedures to demonstrate ductal morphology 
and guide catheter-based ductal occlusion.
Electrocardiogram
• Typical abnormalities are wide P-waves and 
tall R-waves in the caudal leads (II, aVF , III) 
and left precordial leads. • Atrial fibrillation—
observed infrequently; related to marked 
dilatation of the LA; more common in large-  
breed dogs. • With rPDA—findings of RV 
hypertrophy with S-waves in leads I, II, III, 
and right axis deviation are more typical.
• Persistent patency of the ductus arteriosus 
between descending aorta and origin of the 
left PA. • Left-to-right shunting PDA—
pulmonary edema, cardiomegaly (left-sided), 
and dilation of the aorta and PA. • rPDA—
RV hypertrophy, PA dilation, and prominent 
bronchial arteries; ductal diameter is 
invariably very wide, similar to descending 
aorta. Histologic changes of pulmonary 
vascular disease (medial hypertrophy, 
plexiform lesions or necrotizing arteritis).
  TREATMENT
• Manage pulmonary edema with furosemide, 
pimobendan, and, if necessary, oxygen, nitrates, 
and cage rest; following stabilization, promptly 
occlude the PDA. If medical stabilization is 
ineffective, surgery can often relieve CHF . 
• Ductal closure by surgical ligation or various 
catheter-based occlusion techniques (See Web 
Figure 8). These are referral procedures. 
• Schedule stable animals for elective surgery or 
device closure without delay; dogs as young as 
7–8 weeks of age show no higher operative 
mortality. • T reat dogs with erythrocytosis from 
rPDA with rehydration and salting of food to 
encourage water intake. If needed, consider 
periodic phlebotomy to maintain target PCV 
of 62–65%.
ACTIVITY
• Restrict activity until the ductus is closed 
and in all dogs with CHF . • After suture 
removal and first follow-up examination, 
resume normal activity.
DIET
Normal; restrict sodium intake if CHF .CLIENT EDUCATION
• Do not delay treatment as mortality is 
higher and LV function impaired if clinical 
signs or atrial fibrillation develop. 
• Following successful PDA closure and a 2 
week convalescence, most dogs can be treated 
normally.
• Smaller patient sizes (<2.5 kg) are a limiting 
factor with current intravascular PDA 
occlusion devices. • Surgery can generally 
proceed within 24–48 hours of medical 
stabilization. • Surgical therapy involves 
ductal ligation via left thoracotomy; surgical 
and perioperative mortality is <3% at the 
most experienced centers. • Mortality with 
devices is even lower, but complications 
including failure to achieve closure and device 
embolization infrequently occur. • Never 
close a true rPDA as the RV cannot eject 
against the pulmonary vascular resistance. 
PDA with moderate PH and predominately 
left-to-right shunting can often be closed, 
especially in cats, provided pulmonary 
vascular resistance is not fixed. Medication 
trial with sildenafil may be performed 
cautiously to determine degree of vascular 
reactivity in PDA with PH; monitor 
in-hospital for first 24 hours if pursued.
• T reat pulmonary edema with furosemide 
2–4 mg/kg q6–12h PO, SC, IM, or IV as 
required; and pimobendan 0.2–0.3 mg/kg 
q12h PO. These are usually discontinued 
once the PDA is closed. • When closure is 
not an option—if CHF , prescribe furosemide, 
ACE inhibitor such as enalapril 0.5 mg/kg 
q12–24h PO, and pimobendan. • If atrial 
fibrillation develops add digoxin and 
diltiazem (see Atrial Fibrillation and Atrial 
Flutter). An alternative is electrical cardio -
version—this is a reasonable therapy provided 
the ductus can be closed. Refer to a 
cardiologist. • To control severe, life-
threatening CHF—can use direct vasodilators 
such as hydralazine 1–2 mg/kg q12h PO or 
sodium nitroprusside 1–5  μg/kg/min IV to 
reduce left-to-right shunting. Maintain 
systolic blood pressure at 85–90 mmHg. 
Artificial ventilation might be needed. 
• Consider sildenafil at 1–2 mg/kg q8h PO if 
moderate to severe PH is present.
• Left-to-right PDA—drugs that increase 
systemic vascular resistance and arterial blood 
pressure, except as needed for anesthesia and surgery. • rPDA—drugs that cause systemic 
arterial vasodilation and reduce systemic 
arterial blood pressure, including drugs with 
arterial vasodilating effects.
• Measure digoxin levels if prescribed. 
• Monitor arterial blood pressure, renal 
function, and serum electrolytes to identify 
problems related to diuretic and vasodilator 
Aggressive diuresis leading to dehydration or 
hypokalemia exacerbates the risk for digoxin 
toxicity. Sildenafil in a balanced PDA can 
increase pulmonary overcirculation and result 
in left-sided CHF .
• Prostaglandin inhibitors (e.g., indomethacin) 
do not close PDAs effectively in dogs. 
• Hydroxyurea—infrequently considered for 
treatment of severe erythrocytosis unrespon-
sive to phlebotomy. Consult with internist or 
oncologist before using.
  FOLLOW-UP
• Intra- and postoperative pain management 
with opiates and regional blocks as 
appropriate for the procedure. Analgesic 
therapy following catheter-based closure is 
less aggressive but also continued for 24–48 
hours. • Postoperative—vital signs and 
respiratory rate. • Cardiac auscultation 
postoperatively and at suture removal; if heart 
sounds are normal, no further follow-up or 
diagnostic studies are required unless 
preoperative echocardiography showed 
moderate to severe LV dysfunction. There is 
no basis for recommending annual cardiac 
reevaluation of uncomplicated cases. 
• Persistent, continuous murmur indicates 
either incomplete closure of the ductus, 
recanalization (infection or device migration), 
or a concurrent cardiac or vascular defect. 
• Systolic murmurs are variably heard 
postoperatively; these typically abate by the 
time of suture removal. Reinvestigate 
unexpected murmurs by Doppler echocardio -
graphy. When only partial surgical ligation is 
achieved, consider referral for device occlusion.
Do not breed.
• Sudden illness, fever, or acute respiratory 
signs postoperatively—consider bacterial 
infection of the closure site with 
hematogenous pneumonia; aggressive Patent Ductus Arteriosus  (continued)

Canine and Feline, Seventh Edition  1051
Pantibiotic therapy needed. • An unusual 
complication is acquired stenosis of the main 
or branch PA following surgery to correct 
PDA.
• Infrequently dogs remain asymptomatic 
for life. PDA closure adds an estimated 10 
years to median lifespan in dogs (12 years 
with closure, 2 years without). In older 
reports, ∼50–60% of dogs died from CHF 
within 1 year of diagnosis if the PDA was 
not closed. • Closure prior to onset of 
moderate-to-severe CHF—excellent 
prognosis. • Moderate-to-severe CHF is 
related to myocardial failure of LV or atrial 
fibrillation—guarded prognosis; referral to 
a cardiologist is advised. • Dogs with 
rPDA can live for several years but often 
die suddenly; occasionally, dogs live 
beyond 5 years of age (especially cocker 
spaniels). • Cats—varies from rapidly 
progressive left-sided CHF to gradual 
development of pulmonary vascular 
disease; even right-sided CHF can develop 
with PDA and PH.  MISCELLANEOUS
Typically an isolated defect, but is recognized 
with other congenital heart lesions—more 
likely in larger breeds. Occasionally a vascular 
ring anomaly is evident, such as persistent 
right fourth aortic arch.
Presentation is typically young animals; 
median age of presentation reported as 5 
months in dogs.
Greater risk for CHF in pregnant bitches; 
offspring have greater risk for large PDA or 
rPDA; do not breed affected dogs.
SYNONYMS
Duct of Botallo, ductus Botalli, patent arterial 
duct.
SEE ALSO
• Murmurs, Heart.ABBREVIATIONS
• CHF = congestive heart failure.
• LA = left atrium.
• LV = left ventricle.
• PA = pulmonary artery.
• PCV = packed cell volume.
• PDA = patent ductus arteriosus.
• PH = pulmonary hypertension.
• rPDA = reversed patent ductus arteriosus.
• RV = right ventricle.
• VSD = ventricular septal defect.
Dr. James Buchanan Cardiology Library: 
https://www.vin.com/
doc/?id=2993158&pid=84
Beijerink NJ, Oyama MA, Bonagura JD. 
Congenital heart disease. In: Ettinger SJ, 
Louis, MO: Elsevier, 2017, pp. 1207–1218.
Authors  John D. Bonagura and Brian A. 
Scansen
available online(continued)  Patent Ductus Arteriosus

1052  Blackwell’s Five-Minute Veterinary Consult  
PPectus Excavatum
  BASICS
OVERVIEW
• Deformity of the sternum and costal cartilages 
that results in a dorsal-to-ventral narrowing of 
the chest, primarily in the caudal aspect.
• Can have secondary abnormalities of 
respiratory and cardiovascular function from 
restriction of ventilation and cardiac 
• Considered congenital in origin although 
an acquired case has been reported.
• Upper respiratory obstruction at a young 
age could cause abnormal respiratory 
gradients and subsequent pectus excavatum.
• Uncommon defect.
• Concurrent cardiac defects common.
• Some patients demonstrate swimmer 
syndrome—neonatal dogs lack the ability to 
posture properly and remain in sternal 
recumbency, which can lead to invagination 
of the sternum.
• Brachycephalic breeds and Bengal cats are 
• Most common age of presentation—4 
weeks–3 months.
• Male cats more often reported than females, 
no sex predisposition noted in dogs.
SIGNS
• Thoracic defect, easily palpated or seen.
• Varying degrees of respiratory distress.
• Recurrent respiratory infections.
• Cough.
• Poor appetite.
• Cardiac murmurs associated with 
concurrent cardiac defects or compression of 
the heart.
• Muffled heart sounds.
• No correlation between severity of signs 
and severity of anatomic or physiologic 
• Vertebral deformities.
• Swimmer syndrome—limbs not adducted 
properly; ambulation impaired.
• Genetic predisposition—may exist.
• Unknown etiology—suspected causes 
include intrauterine pressure abnormalities, 
shortening of central tendon of the 
diaphragm, cranial abdominal muscle 
deficiency, and abnormal osteogenesis or 
chondrogenesis.• Dogs predisposed to respiratory obstructive 
processes have a higher risk than others.
• Single report in a geriatric golden retriever 
with laryngeal paralysis.
• Puppies raised on surfaces causing poor footing 
may be predisposed to swimmer syndrome.
  DIAGNOSIS
• Congenital diaphragmatic hernia 
(pleuroperitoneal or pericardioperitoneal).
• T racheal malformations or collapse.
• Congenital heart defects.
• T racheobronchitis/bronchitis.
• Brachycephalic obstructive airway syndrome.
IMAGING
Thoracic Radiography (see Web Figure 1)
• Confirm sternal and costal skeletal 
• Decreased thoracic volume.
• Cardiac malpositioning—left and cranial 
displacement of cardiac silhouette.
• Concurrent secondary pulmonary disease.
• Measure frontosagittal and vertebral indices 
to characterize degree of deformity as mild, 
moderate, or severe and help predict response 
to treatment.
• The frontosagittal index is the ratio between 
the width of the chest at the 10th thoracic 
vertebra and the distance between the center of 
the ventral surface of the 10th thoracic vertebral 
body and the nearest point on the sternum.
• The vertebral index is the ratio between the 
distance from the center of the dorsal surface 
of the 10th vertebral body to the nearest 
point on the sternum and the dorsoventral 
diameter of the vertebral body at the same 
level.
Rule out concurrent congenital cardiac 
defects or other cardiac disease.
  TREATMENT
• Decision to repair deformities is made on 
the basis of clinical signs. If it is an incidental 
finding with minimal to no clinical signs, 
then intervention may not be indicated.
• T reatment options include external 
coaptation, partial sternectomy, or both. 
Decision is based on age of the animal and 
degree of deformity.
• Surgery benefits patients with concurrent 
respiratory distress; benefits are unknown in 
patients with no respiratory distress but with 
moderate or severe deformity.• Nonclinical patients can develop signs at a 
later date; patients with clinical signs of 
disease may show progression.
• For puppies with swimmer syndrome, place 
on surfaces with excellent footing; careful 
toggling of front and rear legs may improve 
adduction.
• Brachycephalic breeds with concurrent 
upper airway obstruction may benefit from 
surgery directed at these problems.
• Anesthesia—patients require constant 
monitoring; ventilatory support should be 
N/A
  FOLLOW-UP
• Examinations—dictated by clinical signs or 
when surgical intervention has been 
precluded.
• No specific actions for avoiding disease; 
genetic factors may sometimes be involved.
• Progression of respiratory signs—can 
develop in nonclinical or mildly clinical 
patients.
• Prognosis—guarded to good depending on 
properly timed and expertly administered 
• Cardiac defects.
• Swimmer syndrome.
Charlesworth TM, Sturgess CP . Increased 
incidence of thoracic wall deformities in 
related Bengal kittens. J Feline Med Surg 
2012, 14(6):365–368.
Hassan EA, Hassan MH, Torad FA. 
Correlation between clinical severity and 
type and degree of pectus excavatum in 
twelve brachycephalic dogs. J Vet Med Sci 
2018, 80:766–771.
Kurosawa TA, Ruth JD, Steurer J, et al. 
Imaging diagnosis: acquired pectus 
excavatum secondary to laryngeal paralysis 
in a dog. Vet Radiol Ultrasound 2012, 
53:329–332.
Mestrinho LA, Ferreira CA, Lopes AM, et al. 
Open surgical correction combined with an 
external splint for correction of a non-
compliant pectus excavatum in a cat. J 
Feline Med Surg 2012, 14:151–154.

Canine and Feline, Seventh Edition  1053
PPelger–Huët Anomaly
  BASICS
OVERVIEW
• Congenital hereditary disorder that has 
been seen in several breeds of dogs and 
• Results in nuclear hyposegmentation of 
many to all granulocytes (neutrophils, 
eosinophils, and basophils).
• Hypolobulation of monocytes and 
megakaryocytes has also been reported.
• Chromatin patterns of leukocytes are 
normochromatic, or occasionally hyper­
chromatic, rather than the open, immature 
chromatin of immature leukocytes.
• Cytoplasm of cells is unremarkable (i.e., no 
toxic changes are observed).
• Cell function is unaffected in heterozygotes; 
homozygotes are usually stillborn or die in 
utero.
• Care should be taken not to misinterpret as 
a severe left shift.
• Dogs—Pelger–Huët anomaly (PHA) has 
been reported in mixed ­breed dogs as well as 
numerous pure ­breed animals. Overall the 
incidence is low; however, Australian 
shepherd dogs have been shown to have a 
9.8% incidence rate.
• Cats—PHA has only been reported in 
domestic shorthair cats. The overall incidence 
in cats is unknown; however, it is likely rare 
when compared to dogs.
• An autosomal dominant mode of 
inheritance is likely; however, incomplete 
penetrance has been seen in Australian 
SIGNS
No clinical signs are associated with 
heterozygous animals, as the leukocytes are 
fully functional.
• In humans, caused by an inherited defect of 
the lamin B receptor.
• Australian shepherd dogs are over­
represented in reported canine cases.
  DIAGNOSIS
• The primary differential diagnosis to rule 
out is a severe left shift, indicating severe 
inflammation or infection.
• An inflammatory leukogram may show a 
leukocytosis or leukopenia. Immature 
leukocytes exhibit an open, pale chromatin 
pattern.• Toxic changes (Döhle bodies, blue foamy 
cytoplasm, toxic granulation, etc.) are 
frequently seen with severe inflammation, but 
not PHA.
• Pelger–Huët cells have a nucleus that shows 
a mature, condensed chromatin pattern and 
exhibit no toxic changes.
• Animals with PHA are clinically healthy, 
whereas animals with severe left shifts tend to 
be systemically ill.
• Pseudo ­ or acquired PHA is an acquired 
condition that results in granulocyte 
hyposegmentation, secondary to 
myelodysplastic conditions or drug therapy.
CBC/SERUM BIOCHEMISTRY/
URINALYSIS
• The blood smear reveals a persistent varying 
hyposegmentation of all granulocytes and 
often monocytes.
• Granulocyte nuclei have mature, condensed 
chromatin and may be round, oval, peanut, 
dumbbell, horseshoe, and bilobed in shape.
• The serum biochemistry profile and 
urinalysis are unremarkable.
Examination of a peripheral blood smear 
which exhibits hyposegmentation of all 
granulatocytes is all that is needed to diagnose 
PHA.
IMAGING
Imaging is not useful in diagnosing PHA.
• Establishment of a hereditary pattern 
typically an academic exercise, but potentially 
useful.
• No additional diagnostic procedures are 
indicated to diagnose PHA.
• Additional diagnostics are warranted if an 
underlying disease is suspected to cause a 
severe left shift.
  TREATMENT
No treatment is indicated for PHA.
N/A
  FOLLOW-UP
No follow ­up is necessary.  MISCELLANEOUS
Affected animals should not be bred, as it is 
lethal in utero .
• PHA = Pelger–Huët anomaly.
Latimer KS. Pelger ­Huët anomaly. In: 
Feldman BF , Zinkle JG, Jain NC, eds., 
Schalm’s Veterinary Hematology, 5th ed. 
Philadelphia, PA: Lippincott Williams & 
Williams, 2000, pp. 976–983.

1054  Blackwell’s Five-Minute Veterinary Consult  
PPelvic Bladder
  BASICS
OVERVIEW
Pelvic bladder or “intrapelvic bladder” is 
characterized by abnormal position of the 
urinary bladder neck caudal to the pubic 
bone, causing the proximal urethra and a 
variable portion of the trigone or the body of 
the bladder to remain within the pelvic canal. 
It is commonly associated with a short 
urethral length and urethral sphincter 
mechanism incompetence (USMI).
• Primarily young female dogs (<1 year of age).
SIGNS
• Incontinence can be continuous or 
• Conscious voiding patterns often present.
• Perineum stained/soaked with urine, urine 
scalding, wet vulva/prepuce.
• Urgency with small volume elimination 
The position of the bladder in incontinent 
female dogs has been shown to be more 
intrapelvic and associated with a shorter urethral 
length, suggesting that an intrapelvic bladder 
neck and a short urethra together encourage 
urinary incontinence. It is hypothesized that this 
could result from an unbalanced distribution of 
the pressure exerted by the abdominal organs 
between the bladder and urethra.
  DIAGNOSIS
• Urinary incontinence—ectopic ureter, USMI, 
inappropriate urination, urge incontinence, 
urinary tract infection (UTI), neurogenic 
incontinence, overflow incontinence.
• Often associated with ectopic ureters.
• CBC and biochemistry typically 
• Urinalysis may reveal evidence of a UTI 
(including pyuria, bacteriuria, and hematuria) or 
polyuria (urine specific gravity [USG] <1.035).
• Urine culture and sensitivity via a 
cystocentesis should be performed.
IMAGING
• Abdominal radiographs may reveal a caudally 
displaced bladder, but this should be interpreted 
carefully without bladder distension.
• Excretory urography may allow visualization 
of the kidneys, ureteral terminations, urinary 
bladder, and urethra but does not provide bladder distension. Without bladder 
distension, interpretation of bladder neck 
location should be made with caution.
• Retrograde vaginourethography or 
urethrocystography allows visualization of the 
vaginal vault, urethra, urethral length, 
prostate, urinary bladder shape, and bladder 
neck location.
• If the urinary bladder and urethra are inside 
the bony pelvis, double contrast cystourethro­
graphy may be required for full visualization.
• Ultrasonography of the kidneys, ureters, and 
urinary bladder can aid in documentation of 
concurrent urologic anomalies, hydronephrosis, 
pyelonephritis, or ectopic ureters.
• The diagnostic combination of choice is 
cystourethroscopy with contrast cystourethro­
graphy, allowing investigation of urethral, 
ureteral, urinary bladder, vaginal, and 
vestibular defects. It also allows measurement 
of urethral length and width and aids in 
formulating therapy.
• Neurologic exam should be normal.
• Urodynamic procedures—consider 
cystometrography and urethral pressure 
profilometry to evaluate urinary bladder and 
urethral function, as well as urethral length.
  TREATMENT
• Identify UTI and treat appropriately.
• Goal is to increase urethral resistance 
(intraurethral injections of bulking agents, 
urethral hydraulic occluder, etc.), and/or 
relocate the bladder neck to an intra ­abdominal 
position (colposuspension, urethropexy, 
prostatopexy, or vas deferensopexy).
• Detrusor relaxation may treat refractory 
incontinent dogs with an overactive bladder 
contributing to incontinence or urgency.
• Medical management for traditional USMI is 
typically successful in 75–90% of female dogs.
• Colposuspension has a reported cure rate 
of 53%.
• Placement of a urethral hydraulic occluder, 
also termed “artificial urethral sphincter” has 
been successful and is currently the surgical 
treatment of choice if other minimally invasive 
or medical interventions fail. Experience with 
this procedure has been limited and the risk of 
urethral strictures can be up to 20%. Cystopexy 
can also be considered.
Minimally Invasive Treatment
T ransurethral submucosal bulking agent (e.g., 
collagen) therapy has been described for 
patients refractory to medical management 
and is associated with good, but temporary 
success. While this may improve incontinence, 
it does not alter the location of the urinary 
bladder.  MEDICATIONS
• All should be reduced to lowest effective 
dosage. Combination therapy may be more 
• Phenylpropanolamine (PPA)—an α­agonist 
(1–2 mg/kg PO q8–12h) will improve 
continence in a majority of USMI cases.
• Diethylstilbestrol (DES)—an estrogen 
(0.1–1 mg PO q24h for 3–5 days, then 
0.1–1 mg per week thereafter). DES can be 
toxic to the bone marrow in dogs and cats 
and can cause blood dyscrasias. This can 
progress, in rare cases, to fatal aplastic anemia. 
Estrogenic effects may also be seen.
• Estriol—an estrogen (2 mg once daily per 
dog (regardless of body weight) for 14 days, 
then taper every 7 days). Estriol can be toxic 
to the bone marrow in dogs and cats and can 
cause blood dyscrasias, but is considered safer 
than DES. Estrogenic effects may also be seen.
  FOLLOW-UP
• Monitor for the development of lower 
urinary tract signs which could indicate UTI.
• Patients receiving an α­agonist should have 
serial blood pressure evaluations, as this is 
contraindicated in hypertensive patients or 
those with renal or heart disease.
• Patients receiving estrogen therapy (DES or 
estriol) should have serial CBC evaluations to 
monitor for bone marrow dyscrasia.
• Use all medications at the lowest effective dose.
• DES = diethylstilbestrol.
• PPA = phenylpropanolamine.
• USMI = urethral sphincter mechanism 
Crawford JT, Adams WM. Influence of 
vestibulovaginal stenosis, pelvic bladder, and 
recessed vulva on response to treatment for 
clinical signs of lower urinary tract disease 
in dogs: 38 cases (1990–1999). J Am Vet 
Med Assoc 2002, 221(7):995–999.
Author  Andreanne Cleroux
Allyson C. Berent.

Canine and Feline, Seventh Edition  1055
PPemphigus
  BASICS
• A group of autoimmune dermatoses 
characterized by varying degrees of erosion, 
ulceration, crusting, pustule and vesicle 
formation. • Affects the skin and sometimes 
mucous membranes. • Forms identified in 
animals—pemphigus foliaceus (PF), pemphigus 
erythematosus (PE), pemphigus vulgaris 
(PV), paraneoplastic pemphigus (PP), and 
panepidermal pustular pemphigus (PEP)/
pemphigus vegetans (PVeg).
• Tissue-bound autoantibody directed at 
intraepidermal cell antigens (desmoglein and 
desmocollin) and acetylcholine receptors is 
deposited within the intercellular spaces, 
causing epidermal cell separation and cell 
rounding (acantholysis). • Severity of 
ulceration and disease—related to depth of 
autoantibody deposition within the skin. 
• PF—autoantibody deposition in the 
superficial layers of the epidermis. • PV—
lesions more severe; auto-antibody deposition 
just above the basement membrane zone; 
rapidly leads to ulcer formation. • The disease 
is typically considered to be idiopathic. 
Possible drug association has been proposed 
in dogs and cats with PF . Sunlight exposure is 
suspected to induce flares of PF and PE. 
Thymoma has been associated with 
pemphigus variants in dogs and cats.
Skin/exocrine
• PF—most common autoimmune skin 
disease in dogs and cats. • PE—relatively 
common. • PV/PP—more severe forms, much 
rarer than PF/PE. • PEP/PVeg—rarest form; 
may represent a more severe variant of PF .
Species
PF— Dogs: Akita, chow chow, dachshund, 
cocker spaniel, Labrador retriever, and English 
bulldog. Cats: possibly short-haired and Siamese.
Usually middle-aged to old animals.
SIGNS
PF
• Scales, crust, pustules, epidermal collarettes, 
erosions, erythema, alopecia, and footpad 
hyperkeratosis with fissuring. • Common 
involvement—head, face, ears, and footpads. 
• Most cases develop extensive disease within one month. • Nasal depigmentation may 
develop, but this is a late event. • Head and 
facial distribution is an important distinction 
from a staphylococcal pyoderma. • Cats—
nipple and ungual fold involvement common. 
• Lymphadenopathy, edema, depression, fever, 
and lameness (if footpads involved) when severe 
or generalized. • Variable pain and pruritus. 
• Secondary bacterial infection possible.
PE
• May be a variant of PF or a crossover 
between PF and discoid lupus erythematosus 
(DLE). • Dogs and cats—pustules, erosions 
and crusts on face and pinnae. Along with 
depigmentation, erythema and erosion/
ulceration of the nasal planum and dorsal 
muzzle. Rare patients exhibit nonfacial 
lesions. • Depigmentation more common 
than with other pemphigus forms, often 
precedes crusting.
PV/PP
• Oral cavity lesions frequent and may precede 
skin lesions. • Initially vesiculobullous lesions 
rapidly progressing to ulcerations and erosions. 
• More severe than PF and PE. • Affects 
mucous membranes, mucocutaneous junctions, 
and skin; may become generalized. • Footpads 
and ungual folds may be involved, with 
resultant onychomadesis. • Positive Nikolsky 
sign (new or extended erosive lesion created 
when lateral pressure is applied to the skin near 
an existing lesion). • Variable pruritus and 
pain. • Anorexia, depression, and fever. 
• Secondary bacterial infections common.
PEP/PVeg
• Pustule groups become eruptive 
papillomatous lesions with exudation. • No 
oral involvement. • No systemic illness.
  DIAGNOSIS
PF
• Superficial pyoderma. • Dermatophytosis. 
• Demodicosis. • Candidiasis. • Keratinization 
disorders. • Cutaneous lupus erythematosus 
or DLE. • PE. • Subcorneal pustular 
dermatosis. • Drug eruption. • Zinc-
responsive dermatitis. • Dermatomyositis. 
• Tyrosinemia. • Mycosis fungoides. 
• Metabolic epidermal necrosis. • Linear IgA 
PE
• PF . • DLE. • Mucocutaneous pyoderma. 
• Demodicosis. • Dermatophytosis. 
• Epidermolysis bullosa simplex. 
• Uveodermatologic syndrome.
PV/PP
• Subepidermal blistering diseases. • Systemic 
lupus erythematosus. • Toxic epidermal 
necrolysis. • Drug eruption. • Mycosis fungoides. • Ulcerative stomatitis causes. 
PEP/PVeg
• PF . • PV. • Superficial pyoderma. 
• Lichenoid dermatoses.
• Abnormalities uncommon. • Leukocytosis 
and hyperglobulinemia with chronicity and/
or secondary infection.
Antinuclear antibody—may be weakly 
positive in PE only.
• Cytology of pustules—aspirates or 
impression smears from pustules or under 
crusts: acantholytic keratinocytes (rounded 
and deeply staining isolated keratinocytes) and 
neutrophils; occasionally with eosinophils. 
• Biopsy of pustules or crusted lesions (submit 
crusts with the biopsy samples of the skin).
• Histopathology: ◦ PF—subcorneal pustules 
with acantholytic cells and neutrophils; 
eosinophils often present; follicles may be 
involved. ◦ PE—intragranular and subcorneal 
pustules, eosinophils, neutrophils, lichenoid 
interface dermatitis. ◦ PV—suprabasilar 
intraepidermal cleft with the remaining basal 
cells exhibiting a tombstone appearance. 
◦ PP—suprabasilar clefting with interface 
dermatitis and apoptotic keratinocytes. 
◦ PEP/PVeg—pustules present throughout 
the epidermal layers and includes follicular 
epithelium. • Immunopathology of biopsied 
skin via immunofluorescent antibody assays 
or immunohistochemical testing—may 
demonstrate positive staining in the 
intercellular spaces in 50–90% of cases; 
results can be affected by concurrent or 
previous corticosteroid (or other immuno -
suppressive drug) administration; indirect 
immunofluorescence usually negative; PE 
may demonstrate staining of basement 
membranes and intercellular spaces.
  TREATMENT
• Initial inpatient supportive therapy for 
severely affected patients. • Outpatient 
treatment with initial frequent hospital visits 
(every 1–3 weeks); taper to every 1–3 months 
when remission is achieved and the patient is 
on a maintenance medical regimen.
Severely affected patients may require 
antibiotics and hydrotherapy/soaks.
Sun avoidance/use of sunblock—ultraviolet 
light may exacerbate lesions (PF and PE).

1056  Blackwell’s Five-Minute Veterinary Consult  
PF
Corticosteroids—Dogs
• Prednisone or prednisolone 2 mg/kg/day 
PO divided q12h to initiate control. An 
attempt to reduce this dose should be made 
when the disease undergoes remission. 
• Minimum maintenance—0.5 mg/kg PO 
q48h to twice weekly. • High pulse therapy—  
10 mg/kg once daily for 3 consecutive days, 
followed by standard dosage (<2 mg/kg/day). 
Pulses can be repeated if new lesions continue 
to appear in spite of the lower doses. Pulse 
should not be repeated more than once 
weekly.
Corticosteroids—Cats
• Prednisolone—2 mg/kg/day until clinical 
resolution. Majority of cats achieve disease 
control with corticosteroids monotherapy.
Cytotoxic Agents
• Most patients require additional immuno -
modulating drugs. • Work synergistically 
with corticosteroids to allow reduction in 
dose and side effects. • Azathioprine 1.5–2.5 
mg/kg PO q24h, then q48h. Recommended 
for canine cases that fail to achieve adequate 
control with glucocorticoids alone (dogs only; 
potential for marked bone marrow 
suppression in cats). • Chlorambucil 0.1–0.2 
mg/kg every other day; best option for cats 
with disease control that is not achieved with 
corticosteroid monotherapy. • Cyclosporine 
5–10 mg/kg PO q24h; variable efficacy in 
dogs and cats. • Mycophenolate mofetil 
10–20 mg/kg twice daily.
PE
• Oral prednisone or prednisolone 1.1 mg/kg 
PO q24h; then q48h; then to the lowest 
maintenance dose possible; may be stopped 
when in remission. • Topical steroids may be 
sufficient in mild cases. • Topical tacrolimus.
PV
• Aggressive therapy with corticosteroids and 
azathioprine or chlorambucil + systemic 
PP
azathioprine or chlorambucil + systemic antibiotic therapy. • Identification and 
treatment or removal of underlying neoplasia.
PEP/PVeg
• T reatment similar to PF . • Response more 
variable; some patients may achieve remission 
with conservative treatment.
• Corticosteroids—polyuria, polydipsia, 
polyphagia, temperament changes, diabetes 
mellitus, pancreatitis, and hepatotoxicity. 
• Azathioprine—pancreatitis, bone marrow 
suppression. • Cytotoxic drugs—leukopenia, 
thrombo  cytopenia, nephrotoxicity, 
hepatotoxicity, and gastrointestinal upset. 
• Immunosuppression—can predispose 
animal to demodicosis, cutaneous and 
systemic bacterial and fungal infection.
Alternative Corticosteroids
• Use instead of prednisone if undesirable 
side effects or poor response noted. 
• Methylprednisolone 0.8–1.5 mg/kg PO 
q12h; for patients that tolerate prednisone 
poorly. • T riamcinolone or dexamethasone 
0.2–0.3 mg/kg PO q12h; then 0.05–0.1 mg/
kg q48–72h.
Topical Steroids
• Hydrocortisone cream. • Potent topical 
corticosteroids—0.1% betamethasone 
valerate, fluocinolone acetonide, or 0.1% 
triamcinolone; q12h; then q24–48h.
• PE cases—doxycycline 5 mg/kg twice daily 
and niacinamide 500 mg twice daily for dogs 
>10 kg; 250 mg for dogs <10 kg.
  FOLLOW-UP
• Monitor response to therapy. • Monitor for 
medication side effects—routine hematology 
and serum biochemistry, especially patients 
on high doses of corticosteroids and cytotoxic 
drugs; check every 1–3 weeks, then every 1–3 
months when in remission.
PV and PF
• Dogs—poor (PV/PP) to fair (PF/PEP): 
life-long or long-term therapy with 
corticosteroids and cytotoxic drugs usually needed; good (PE): relatively benign and 
self-limiting. • Cats—good (PF), but 
long-term treatment required, tendency to 
relapse spontaneously or with treatment 
changes. • Regular monitoring necessary. 
• Side effects of medications may affect 
quality of life. • May be fatal if untreated 
(especially PV). • Secondary infections cause 
morbidity and possible mortality 
(especially PV).
Avoid steroids and cytotoxic drugs during 
• PEP/PVeg = panepidermal pustular 
pemphigus/pemphigus vegetans.
• PP = paraneoplastic pemphigus.
Ackermann AL, May ER, Frank LA. Use of 
mycophenolate mofetil to treat immune-
mediated skin disease in 14 dogs: a 
retrospective evaluation. Vet Dermatol 
2017, 28:195–e44.
Bizikova P , Burrows A. Feline pemphigus 
foliaceus: original case series and a 
comprehensive literature review. BMC Vet 
2019, 15:22.
Bizikova P , Olivry T. Oral glucocorticoid 
pulse therapy for induction of treatment of 
canine pemphigus foliaceus—a comparative 
study. Vet Dermatol 2015, 26:354–e77.
Resnick
Helton Rhodes. 
available onlinePemphigus  (continued)

Canine and Feline, Seventh Edition  1057
PPerianal Fistula
  BASICS
OVERVIEW
Chronic inflammatory condition 
characterized by multiple, painful, 
progressive, ulcerating sinuses or, less 
frequently, true fistulous tracts involving the 
perianal region.
• Dog. • German shepherd dogs primarily; 
Irish setters. • Mean age 5–7 years; range 7 
months–14 years. • Males more commonly 
affected.
SIGNS
• Dyschezia. • Tenesmus. • Hematochezia. 
• Constipation. • Diarrhea. • Malodorous 
mucopurulent anal discharge. • Ulceration of 
the perianal skin with sinus tract formation. 
• Licking and self-mutilation. • Reluctance 
to sit; posturing difficulties; personality 
changes. • Pain on manipulation of tail and 
examination of perianal area. • Fecal 
incontinence. • Anorexia. • Weight loss.
• Multifactorial immune-mediated 
mechanism is suspected. • Appears to be an 
inappropriate T-cell mediated response. 
• An association with colitis has also been 
proposed, particularly in German shepherd 
dogs. • A genetic predisposition has been 
proposed but not proven. • Low tail 
carriage and a broad-based tail may 
contribute in German shepherd dogs. 
• High density of apocrine sweat glands in 
the cutaneous zone of the anal canal of 
German shepherd dogs.
  DIAGNOSIS
• Other inflammatory processes—e.g., 
anusitis, hydradenitis suppurativa. • Chronic 
anal sac abscess. • Perianal adenoma or 
adenocarcinoma with ulceration and 
drainage. • Squamous cell carcinoma. 
• Atypical bacterial infection. • Oomycosis. 
• Rectal fistula.
• Usually unremarkable. • May have an 
• Presumptive diagnosis—clinical signs and 
physical examination. • Definitive 
diagnosis—biopsy of the affected area. 
• Colonoscopy with biopsy—may reveal 
associated colitis.  TREATMENT
• Outpatient medical therapy recommended 
initially in all cases. • Clipping and cleaning 
the perianal area facilitates local therapy. 
• Bathing with an antimicrobial shampoo may 
be helpful. • Dietary modification—strictly 
enforced hydrolyzed or novel protein 
elimination diet. • Stool softeners—with pain 
or tenesmus. • Surgery is considered for 
patients with incomplete resolution following 
appropriate medical therapy. • Anal 
sacculectomy—if anal sac involvement. 
• Surgical options—resection of inflammatory 
tissue and/or ablation of remaining sinuses 
with carbon dioxide laser is preferred. 
• Surgical debridement (deroofing) with 
fulguration by chemical cautery or 
electrocautery; surgical resection followed by 
primary closure or second intention healing are 
other options. • Radical excision of the rectal 
ring with modified rectal pull-through is rarely 
necessary and is associated with a higher risk of 
fecal incontinence.
• Cyclosporine (CsA) ± ketoconazole is 
treatment of choice but is expensive. 
Ketaconazole reduces dose of cyclosporine 
required by inhibiting CsA-metabolizing 
enzymes: ◦ Give CsA orally at 1–5 mg/kg/day 
PO and ketoconazole at 5–10 mg/kg/day PO 
and then taper CsA as clinical signs resolve. 
◦ Continue treatment at least 4 weeks after 
complete resolution of fistula(e). Many 
patients require chronic treatment at reduced 
frequency to prevent recurrence. • Tacrolimus 
(0.1% ointment) topically as maintenance 
therapy may be sufficient to control lesions; 
begin application as dose of oral medications is 
reduced: ◦ Apply q12h with gloved hand, then 
taper to q24–72h. • Oral prednisone and 
topical tacrolimus appears to be efficacious and 
economical in less severe cases: ◦ Prednisone 2 
mg/kg PO q24h for 2 weeks, decrease to 1 mg/
kg q24h for 4 weeks and then 1 mg/kg q48h 
for 10 weeks. ◦ Tacrolimus 0.1% ointment as 
above. ◦ Chronic maintenance therapy with 
tacrolimus and possibly prednisone likely 
necessary for long-term control. 
• Azathioprine alone or combined with 
prednisone is another treatment option.
• Analgesics may be necessary. 
• Metronidazole 10 mg/kg q12h for 2 weeks 
at initiation of therapy to control secondary 
infection.  FOLLOW-UP
• Assess CsA trough levels if improvement is 
not seen or if toxicity is suspected. 
• Reexamine to assess healing, signs of 
recurrence, and associated complications.
• Reversible alopecia. • Vomiting, diarrhea, 
anorexia. • Weight loss. • Recurrence. 
• Failure to heal. • Surgical dehiscence. 
• Tenesmus. • Fecal incontinence. • Anal 
stricture. • Flatulence. • Iatrogenic Cushing’s 
disease from corticosteroids. • Gingival 
hyperplasia from CsA.
• Guarded for complete resolution except in 
mildly affected patients. • Chronic treatment 
• Colitis.
• Constipation and/or obstipation may 
develop.
• CsA = cyclosporine.
Fallipowicz D. Nonsurgical management of 
perianal fistulae. In: Bojrab MJ, Waldron 
D, Tombs JR, eds., Currrent Techniques in 
Small Animal Surgery, 5th ed. Jackson, KY: 
Teton Newmedia, 2014, pp. 309–315.
Pieper J, McKay L. Perianal fistulas. 
Compend Contin Educ Vet 2011, 
33(9):E4.
Author  Eric R. Pope
Consult ing Editor  Mark P . Rondeau

1058  Blackwell’s Five-Minute Veterinary Consult  
PPericardial Disease
  BASICS
Pericardial diseases include pericardial 
effusion (PE), constrictive pericardial 
disease, and space-occupying entities in the 
pericardial space. PE can be defined as an 
abnormally high volume of fluid within the 
pericardial sac; cardiac tamponade refers to 
the clinical syndrome that results from 
reduced cardiac output due to mechanical 
compression of the heart. Constrictive 
pericardial disease results when a markedly 
thickened and fibrotic pericardium limits 
the diastolic filling of the heart. Examples of 
space-occupying pericardial disease can 
include large masses in the pericardial space 
and peritoneopericardial diaphragmatic 
hernia (PPDH).
• All pericardial diseases cause diastolic 
dysfunction, resulting in elevation and 
equalization of ventricular and venous 
pressures and reduced cardiac output.
• Accumulation of effusion exceeds the elastic 
capabilities of the pericardial sac, resulting in 
elevated intrapericardial pressure. Cardiac 
tamponade occurs when intrapericardial 
pressure exceeds cardiac diastolic filling 
pressures. The compliant right atrium and 
right ventricle normally have the lowest filling 
pressures and are thus predominantly affected. 
Cardiac tamponade is present when intraperi-
cardial pressures exceed the central venous 
pressure. The resultant reduction in cardiac 
venous return diminishes cardiac output. 
Animals with acute effusions typically exhibit 
signs of weakness or collapse. If intrapericar-
dial pressure exceeds central venous pressure 
continuously for more than a few minutes, 
death occurs.
• Constrictive pericardial disease directly 
restricts diastolic filling, causes dissociation of 
intracardiac and intrathoracic pressures and 
increases interventricular interdependence.
• In animals with chronic pericardial disease, 
low cardiac output activates compensatory 
mechanisms that lead to fluid accumulation, 
typically manifested as right-sided congestive 
heart failure (CHF).
• Cardiovascular—signs of low cardiac 
output and CHF .
• Hepatobiliary—chronic passive congestion 
with mildly to moderately high liver enzymes.
• Respiratory—tachypnea or pleural effusion.
• Gastrointestinal—vomiting seen in some 
cases.
GENETICS
N/AINCIDENCE/PREVALENCE
Pericardial disorders comprise approximately 
4–8% of the canine cardiology caseload at 
referral institutions.
Worldwide distribution; increased incidence 
of coccidioidomycosis-induced effusive 
constrictive pericarditis in the southwestern 
United States, Mexico, and Central and 
South America.
Species
Dog; PE in cat is often secondary to CHF .
• Golden retrievers and German shepherd 
dogs are predisposed to both right atrial 
hemangiosarcoma (HSA) and idiopathic 
effusion.
aortic body tumors (chemodectoma 
common in Boston terrier, boxer and 
bulldogs).
• Idiopathic hemorrhagic pericarditis is 
more common in young to middle-aged, 
large-breed dogs (e.g., Great Pyrenees, 
Great Dane, Saint Bernard, golden 
retriever).
Male dogs may be predisposed to idiopathic 
effusion.
SIGNS
Chronic PE often causes jugular distension 
and ascites without a murmur. Acute cardiac 
tamponade often results in collapse and signs 
of low cardiac output.
• Respiratory distress; occasionally cough.
• Syncope or collapse.
• Jugular vein distension.
• Ascites (especially with chronic effusion).
• Weak arterial pulses.
• Pulsus paradoxus.
• Pallor or slow capillary refill time.
• Tachypnea and/or tachycardia.
CAUSES
• Neoplasia—HSA, heart base tumor, thyroid 
adenoma/carcinoma, mesothelioma, 
metastatic neoplasia, and lymphosarcoma 
(LSA) (especially cats).• Idiopathic—pericarditis (benign 
hemorrhagic effusion vs. effusive constrictive 
pericarditis with pericardial fibrosis).
• Coagulopathy—anticoagulant rodenticide 
toxicity, other coagulopathies.
• CHF (especially cats).
• Infection—feline infectious peritonitis 
(FIP), coccidioidomycosis, bacterial 
• Congenital disorders—PPDH, 
intrapericardial cysts.
• Left atrial tear or cardiac trauma.
• Pericardial foreign body.
• Advanced myxomatous mitral valve disease.
  DIAGNOSIS
• CHF secondary to other causes (e.g., 
valvular disease, cardiomyopathy, congenital 
heart disease such as tricuspid valve dysplasia, 
myocarditis), hepatic failure, abdominal 
neoplasia with hemorrhage, protein-losing 
nephropathy or enteropathy, Budd– 
Chiari-like syndrome.
• Other causes of ascites (e.g., hepatic failure, 
hypoproteinemia, intraabdominal neoplasia, 
and hemorrhage)—characteristically result in 
remarkable abnormalities on CBC and 
biochemistry profile, with a lack of jugular 
venous distension.
• Other causes of collapse and shock with low 
cardiac output signs such as sepsis, trauma, 
cardiac arrhythmias, blood loss and tension 
• CBC—usually normal; anemia possible 
with HSA, LSA, or coagulopathy; red cell 
morphology may be abnormal; may see 
thrombocytopenia with neoplasia or 
disseminated intravascular coagulation 
(DIC).
• Biochemistry profile—often normal; may 
see mild to moderately elevated liver enzymes 
(hepatic congestion), mild azotemia (typically 
prerenal), hypoproteinemia, and mild electrolyte 
abnormalities (e.g., hyponatremia, hypochlo-
remia, and hyperkalemia).
• Urinalysis—usually normal unless diuretics 
• Elevated serum cardiac troponin I 
demonstrated in dogs with PE, especially with 
HSA.
• Clotting times (e.g., activated partial 
thromboplastin time and one-stage 
prothrombin time)—prolonged with 
anticoagulant rodenticide toxicity or DIC.

Canine and Feline, Seventh Edition  1059
P• Pericardial fluid analysis, although limited 
in diagnostic sensitivity and specificity, may 
be helpful in identifying certain neoplastic 
etiologies (e.g., LSA) or infectious causes.
• FIP testing or feline leukemia virus testing 
may be useful in cats.
IMAGING
• Mild-to-severe cardiomegaly; cardiac 
silhouette often globoid with very sharp edges 
most evident on the dorsoventral view due to 
lack of cardiac motion artifact. Cardiac size 
sometimes normal.
• Pleural effusion in some patients.
• Ascites in many patients.
• Large caudal vena cava in some patients.
• May see nodular pulmonary infiltrates with 
• Ideally prior to pericardiocentesis in stable 
patients to facilitate detection of intraperi -
cardial masses.
• Superior diagnostic test to diagnose PE and 
evaluate for a cardiac mass (depends on 
operator skill); only moderate accuracy in 
predicting histopathologic diagnosis of masses.
• Echo-free space between the parietal 
pericardium and the epicardium.
• Often demonstrates the cause of PE in 
patients with neoplasia (e.g. right atrial HSA 
or heart base tumor) or PPDH.
• Left atrial rupture suspected based on 
concurrent findings of PE and advanced 
chronic valvular disease, especially if an 
intra-atrial or intra-pericardial thrombus is 
• Diastolic collapse of the right atrium or 
ventricle indicates cardiac tamponade.
Cardiac MRI has not been found to be 
superior to echocardiography in detecting 
cardiac neoplasia to date; CT may be helpful 
in detecting pulmonary, hepatic, or splenic 
ECG
• Often sinus tachycardia; occasionally 
ventricular or supraventricular arrhythmias.
• May see low-voltage QRS complexes ( <0.9 
mV in leads I, II, III, aVR, aVL, and aVF).
• May see ST segment elevation in leads II, 
aVF , V3.
• May see electrical alternans, a regular (1:1 
or 2:1) variation in QRS-T wave height or 
morphology, due to swinging of the heart 
within the pericardial sac.
Pericardial Fluid Analysis
Cytology of PE cannot reliably differentiate 
the common neoplastic (e.g., HSA, chemo -
dectoma, mesothelioma) and idiopathic 
causes of effusion. Cytology can identify or 
rule out some potential causes of effusion (e.g., LSA, FIP , sepsis). If an infectious agent 
is suspected, aerobic and anaerobic cultures of 
the effusion are indicated.
• Vary based on the underlying cause of 
pericardial disease.
• Small masses may be identified that were 
not visible on antemortem testing.
• Dogs with left atrial tears will have 
advanced mitral degeneration with thickened 
and irregular mitral and/or tricuspid valve 
leaflets, left atrial enlargement and 
endocardial jet lesions, and possible ruptured 
chordae tendineae.
• Mesothelioma can be difficult to 
differentiate from idiopathic pericardial 
disease in some dogs, even with 
histopathology.
  TREATMENT
Cardiac tamponade warrants immediate 
pericardiocentesis. Repeated pericardio -
centesis may be needed; surgery may be 
indicated in selected dogs. Pericardio -
centesis is rarely required in the cat.
• Sedation with low-dose narcotic may be 
appropriate, except if moribund. Patient may 
be placed in sternal or lateral recumbency. 
Clip haircoat on the right or left thorax 
between the 3rd and 8th intercostal spaces 
from above the costochondral junction 
ventrally to the sternum. Simultaneous ECG 
and/or echocardiographic monitoring is ideal 
to confirm the presence of the catheter tip in 
the pericardium and detect arrhythmias 
caused by the catheter contacting the heart. If 
echocardiography is not available, perform 
pericardiocentesis at the 5th intercostal space 
(at the palpable apex beat) below the 
costochondral junction. Following aseptic 
skin preparation and local anesthetic block of 
the skin, subcutaneous tissues and pleura with 
lidocaine, advance a long, large-bore ( ∼14–18 
gauge), preferably fenestrated, over-the-needle 
catheter into the pericardial sac. In dogs, PE 
is usually hemorrhagic, but some patients 
have a serous, serosanguinous, or purulent 
effusion. If echocardiography is available, 
removal and reinjection of approximately 
1 mL of pericardial fluid causes visible 
spontaneous echo contrast to appear in the 
pericardial space, confirming catheter 
placement. Remove as much effusion as 
possible (unless active bleeding is suspected). 
If ventricular arrhythmias develop, reposition 
the catheter and be prepared to administer IV 
lidocaine.
• Unless the patient has active hemorrhage 
into the pericardial sac, the effusion obtained by pericardiocentesis should not clot, and 
should have a packed cell volume that differs 
from that of peripheral blood. The 
supernatant of chronic effusions is often 
xanthochromic.
Unless there is marked dehydration, fluids are 
generally not required or recommended for 
chronic PE. Mild volume expansion may be 
useful in some animals with acute PE and 
signs of cardiovascular collapse. Administer 
oxygen if tachypneic or signs of hemodynamic 
instability.
ACTIVITY
Cage rest for animals with cardiac 
tamponade, followed by exercise restriction 
after pericardiocentesis.
DIET
N/A
Inform that PE is typically recurrent in 
nature, though prognosis may vary greatly 
depending on the underlying cause. Educate 
about the importance for close monitoring 
for recurrent effusion and warn of the 
• Pericardiectomy may be useful in the 
treatment of recurrent cardiac tamponade 
for PE accompanying heart base tumors 
and prolongs survival; this may also be 
considered for palliation of right atrial HSA 
but whether it has any impact on survival is 
unknown.
• Idiopathic PE may respond to pericardio -
centesis; pericardiectomy is indicated for 
recurrent effusion.
• Infectious pericarditis due to bacterial 
cause, and pericardial foreign bodies, is 
usually best treated surgically to avoid 
subsequent constrictive pericardial disease.
• Right auricular appendage masses may be 
treated surgically but resection alone without 
adjuvant chemotherapy is unlikely to 
significantly prolong survival.
• Thoracoscopy allows for partial pericardiectomy 
with reduced risk and reduced postoperative 
pain. However some surgeons believe that 
extensive pericardiectomy is preferred in cases 
of benign PE to avoid the possibility of 
recurrent pleural effusion.
• Constrictive pericardial disease is usually 
best treated surgically.
• PPDH is treated surgically when clinical signs 
referable to the defect are clearly present; the 
diagnosis is sometimes established incidentally 
and the need for surgery is uncertain.
• Radiation therapy may also play a role in 
management of pericardial disease due to 
certain neoplastic causes, although concerns 
exist about the development of radiation-
induced cardiac injury or cardiac arrhythmias.(continued)  Pericardial Disease

1060  Blackwell’s Five-Minute Veterinary Consult  
• Drugs should not be used in place of 
pericardiocentesis.
• Vitamin K—indicated for patients with 
anticoagulant rodenticide intoxication.
• Appropriate antibiotics or antifungals are 
indicated with infectious pericarditis.
• Chemotherapy—may be useful to treat 
effusion caused by LSA; partially effective in 
the treatment of atrial HSA and generally 
ineffective for heart-base tumor; adjuvant 
doxorubicin-based chemotherapy following 
right atrial mass resection has been shown to 
increase survival times but dogs rarely survive 
more than 6 months postoperatively.
• In a double blind, randomized study in 
dogs with splenic HSA, a mushroom extract 
delayed the progression of metastases and 
afforded the longest survival times reported in 
canine HSA.
• Some clinicians use antifibrinolytic drug 
(aminocaproic or tranexamic acid) or other 
possible clot-stabilizing drugs (Yunnan 
Baiyao) in an attempt to reduce recurrent 
bleeding, although the efficacy of these 
compounds is uncertain.
Diuretics may worsen tamponade by reducing 
circulating blood volume, and hence 
intracardiac pressures, and can lead to 
progressive azotemia, patient weakness and 
collapse. Digitalis, vasodilators, and 
angiotensin-converting enzyme inhibitors are 
reported to be relatively or absolutely 
contraindicated. Corticosteroids or other 
immunosuppressive drugs may exacerbate 
infection, if present.
N/A
• Intracavitary chemotherapy may be 
attempted to treat mesothelioma, especially in 
cases with recurrent pleural effusion after 
pericardiectomy.
• Anti-inflammatory, immunosuppressive, or 
antifibrotic strategies have been tried in dogs with idiopathic PE (e.g., corticosteroids, nonsteroidal 
anti-inflammatory drugs, azothiaprine, or 
colchicine); efficacy of these strategies for 
preventing recurrent effusion is unknown.
  FOLLOW-UP
PE may recur at any stage; examination and 
echocardiography at 10–14 days and every 
2–4 months recommended to detect 
recurrent idiopathic PE.
• Hypotension or shock.
• Pneumothorax, arrhythmias, and myocardial 
perforation or coronary laceration secondary 
to pericardiocentesis.
• Right atrial HSA—poor; tumor is highly 
malignant, usually not resectable at the time 
of diagnosis; may respond transiently to 
doxorubicin-based chemotherapy; the benefit 
of palliative pericardiectomy is unproven.
• Chemodectoma—fair; slow-growing tumor, 
late to metastasize; pericardiectomy often 
resolves clinical signs; may respond to 
chemotherapy or radiation therapy; survival 
of up to 3 years has been reported following 
pericardiectomy alone. Large masses 
sometimes cause compression of cardio -
vascular structures that might be resolved 
with IV stent placement.
• Prognosis is good with idiopathic PE; 
approximately 50% of cases resolve after one 
or two pericardiocenteses; pericardiectomy is 
often curative in persistent cases, although 
recurrent pleural effusion is seen in some dogs 
Splenic HSA.
• Idiopathic PE may be more common in 
middle-aged to elderly dogs.• HSA and heart-base tumors more common 
in elderly dogs.
SYNONYMS
• Cardiac tamponade.
SEE ALSO
• Myocardial T umors.
• LSA = lymphosarcoma.
• PE = pericardial effusion.
Brown DC, Reetz J. Single agent 
polysaccharopeptide delays metastases and 
improves survival in naturally occurring 
hemangiosarcoma. Evid Based Complement 
Alternat Med 2012, 2012:384301.
Coleman AE, Rapoport GS. Pericardial 
disorders and cardiac tumors. In: Smith 
FWK, Tilley LP , Oyama MA, Sleeper MM, 
eds., Manual of Canine and Feline 
Saunders Elsevier, 2016, pp. 198–217.
Nelson OL, Ware WA. Pericardial effusion. 
MO: Saunders Elsevier, 2014, pp. 816–823.
Authors  John E. Rush and Bruce W. Keene
Consulting Editor  Michael Aherne 
available onlinePericardial Disease  (continued)

Canine and Feline, Seventh Edition  1061
PPerineal Hernia
  BASICS
OVERVIEW
• Perineal hernia (PH) refers to a spectrum 
of disorders in which the pelvic diaphragm is 
weakened, with rupture or atrophy of the 
muscles. Rectal sacculation and dilation 
often occur. This results in abnormal 
function during defecation and, if left 
untreated, leads to herniation of pelvic and 
abdominal viscera.
• Weakening of the pelvic diaphragm in 
male dogs is postulated to result from 
hormonal influences and by increased 
pressure secondary to enlargement of the 
prostate.
• Separation of the perineal muscles (levator 
ani and coccygeus) from the external anal 
sphincter (EAS) and rectum allows lateral 
and ventral bulging and sacculation of the 
rectum when caudal abdominal pressure 
increases during defecation. Feces become 
entrapped within the sacculated rectum, 
contributing to the uncoordinated defecation 
often presented in patients with PH. 
Separation and weakening of the muscles also 
allows pelvic and abdominal viscera to 
migrate caudally, enter the hernia sac, and 
eventually become incarcerated or 
strangulated.
Intact male dogs are at highest risk. The 
disease occurs rarely in castrated male dogs, 
female dogs, and cats.
SIGNS
• Constipation is the main feature, 
although some patients present with 
diarrhea as looser stool escapes around the 
firmer stool.
• Unilateral or bilateral perineal bulge due to 
fecal impaction and/or herniation:
◦ May be dynamic or static.
◦ May become more obvious during events 
of increased intra-abdominal pressure—
barking, coughing, defecation, and 
urination.
◦ Often the only presenting sign in cats.
• Straining to urinate if bladder incarceration 
occurs.
• Intact status in older male dogs and male 
dogs with unilateral or bilateral cryptor-  
chidism.
• Underlying pathology leading to excessive 
straining:
◦ Prostatomegaly in male dogs.
◦ Megacolon and malunion of pelvic 
fractures in cats.
• Caudal neuropathy, malformation or injury 
such as tail traction or avulsion.
• T rauma (rare).  DIAGNOSIS
• Other causes of straining during defecation or 
urination include perineal or intrapelvic mass:
◦ Neoplasia (adenoma, lipoma, adeno -
carcinoma, sarcoma).
◦ Sublumbar lymphadenomegaly secondary 
to anal sac adenocarcinoma.
◦ Rectal tumor.
◦ Paraprostatic cyst or abscess.
◦ Perineal abscess (e.g., anal sac).
No specific abnormalities. Azotemia if urinary 
obstruction occurs.
N/A
IMAGING
• Abdominal radiography—evaluate 
constipation or obstipation, prostatomegaly, 
sublumbar lymphadenomegaly, location of 
urinary bladder and prostate, and megacolon 
in cats.
• Pelvic radiography—evaluate pelvic fracture 
malunion, intrapelvic mass, caudal 
displacement of the prostate and bladder, 
entrapment of bladder or bowel in hernia.
• Abdominal ultrasonography—evaluate the 
size and consistency of the prostate, location 
of urinary bladder and prostate, intrapelvic or 
caudal abdominal masses, sublumbar 
lymphadenomegaly, presence of abdominal 
cryptorchid testicle.
• Perineal ultrasonography—evaluate 
presence of abdominal viscera or masses.
• Visual perianal examination:
◦ Normally the anus and EAS are held in 
position dorsal and slightly cranial to the 
caudal extent of the tuber ischii.
◦ When the perineal diaphragm is 
weakened, the anus migrates caudally. May 
be severe in bilateral PH.
◦ Eliciting a cough reflex by gentle tracheal 
palpation will increase intra-abdominal 
pressure and aid evaluation of the position 
and movement of the anus.
• Rectal examination:
◦ Confirm accumulation of feces in the dilated 
and sacculated rectum and perineal laxity.
◦ If the integrity of the pelvic diaphragm 
has been compromised, it will be possible 
to pinch the rectal mucosa and skin 
together between the tip of the forefinger 
and thumb without palpating a muscle 
shelf in between.
◦ Evaluate both sides; bilateral PH is 
common especially in intact male dogs.
• Endoscopy or percutaneous fine-needle 
aspiration biopsy may be indicated if a mass 
lesion is present extra- or intraluminally.  TREATMENT
• Surgical management required for definitive 
treatment:
◦ Emergency if bladder retroflexion and 
entrapment, or intestinal entrapment have 
occurred.
• Conservative treatment may temporarily 
ameliorate clinical signs:
◦ Low residue diet.
◦ Stool softeners.
• IV fluid therapy in the pre- and post -
operative period.
• Incisional icing postoperatively.
• Elizabethan collar postoperatively.
Activity
Restrict for at least 3–4 weeks following 
Diet
• Low-residue canned diet:
◦ Part of conservative medical management.
◦ Postoperatively.
N/A
• Castration of male dogs should always be 
performed simultaneously with herniorrhaphy, 
due to the high rate of recurrence in intact 
dogs regardless of surgical technique used.
• In patients with bladder retroflexion and 
entrapment, the urethra should be catheterized, 
and the bladder decompressed if possible:
◦ Percutaneous perineal cystocentesis may 
be required to decompress and reposition 
the bladder before a urethral catheter can be 
passed.
◦ If the bladder is able to be decompressed, 
correction of biochemical abnormalities is 
preferred prior to anesthesia and surgery in 
the urinary obstruction patient with PH.
• Prior to surgical correction, the author 
prefers the use of an epidural with local 
anesthetic and/or morphine.
• Impacted feces should be gently removed 
from the rectum prior to surgery:
◦ Enemas are not recommended as liquid 
feces may not be completely evacuated, 
leading to excessive contamination during 
surgery and postoperatively.
• Primary repair of the weakened muscles 
alone often leads to recurrence and is not 
recommended as the only form of repair.
• The internal obturator muscle flap is the 
preferred local method of repair combined 
with primary bolstering of the perineal 
musculature. The author prefers to repair 
both sides of the pelvic diaphragm regardless 
of the unilateral nature of the hernia.
• It may be helpful in large dogs with large 
bilateral hernias, especially if bladder

1062  Blackwell’s Five-Minute Veterinary Consult  
Pretroflexion or visceral entrapment, to 
perform exploratory laparotomy, reposition 
the bladder and rectum, and perform 
incisional colopexy and cystopexy:
◦ Herniorrhaphy can be performed at a 
later time (2–7 days), when the patient’s 
condition has stabilized and the perineal 
edema has resolved.
◦ In patients with poor perineal muscle 
development and in patients with large 
defects, the repair is often bolstered with 
the use of secondary local muscle flaps.
◦ Absorbable and nonabsorbable mesh 
implants are needed in some severe cases.
◦ A superficial gluteal muscle flap is 
recommended in cats and very small dogs 
to bolster the internal obturator muscle flap 
and primary repair techniques.
• Stool softeners may be considered as a 
component of conservative medical 
management or prior to surgery:
◦ Lactulose 0.5–1 mL/kg PO q8–12h, 
adjusted to effect.
◦ PEG 3350 (MiraLax®) ¼–1 tsp on food 
q12h, adjusted to effect.
◦ Goal is 2–3 soft-formed stools per day.
• Intraoperative antibiotics may be given, but 
there is no indication to continue antibiotic 
treatment postoperatively unless significant 
contamination occurs during surgery.CONTRAINDICATIONS/POSSIBLE 
Avoid stool softeners postoperatively, as they 
may lead to diarrhea and fecal soiling in the 
first days after surgery, especially if a bilateral 
repair has been performed.
  FOLLOW-UP
• The patient should be evaluated frequently 
for the first 48 hours following surgery, with 
particular attention paid to urination and 
defecation regardless if bladder entrapment 
was present preoperatively.
• A rectal examination should be performed 
at the time of suture removal (10–14 days) if 
feasible.
• Castration.
• Address conditions causing straining during 
defecation and urination, if present.
• Constipation, obstipation, and bladder 
retroflexion/obstruction, visceral entrapment, 
and strangulation.
• Postoperative complications include 
recurrence (greatly reduced by castration and 
use of internal obturator flap), and temporary 
or permanent dysfunction of the anal 
sphincter due to stretching following bilateral 
herniorrhaphy:
◦ Fecal and urinary incontinence can occur 
if excessive dissection around the pudendal 
nerve, caudal rectal nerve, or peritoneal 
reflections are performed.EXPECTED COURSE AND PROGNOSIS
• Excellent with surgery.
• There is a 10–50% risk of recurrence 
depending on presence of underlying 
conditions, surgical technique, and 
reproductive status of the dog.
Primary conditions causing excessive straining 
(e.g., megacolon in cats).
• EAS = external anal sphincter.
• PH = perineal hernia.
Gill SS, Barstad RD. A review of the surgical 
management of perineal hernias in dogs. J 
Am Anim Hosp Assoc 2018, 4:179–187.
Mann F . Serum testosterone and estradiol 
17-beta concentrations in 15 dogs with 
perineal hernia. J Am Vet Med Assoc 1989, 
194:1578–1580.
Souza CH, Mann T. Perineal hernias. In: 
Monnet E, ed., Small Animal Soft Tissue 
Surgery. Hoboken, NJ: Wiley Blackwell, 
2013, pp. 286–296.
Szabo S, Wilkens B, Radasch, RM. Use of 
polypropylene mesh in addition to 
obturator transposition: a review of 59 cases 
(2000–2004). J Am Anim Hosp Assoc 
2007, 43:136–142.
Consulting Editor  Mark P . RondeauPerineal Hernia  (continued)

Canine and Feline, Seventh Edition  1063
PPeriodontal Disease
  BASICS
Inflammation and destruction of the 
periodontium (i.e., gingiva, cementum, 
periodontal ligament, and alveolar bone) 
secondary to the subgingival biofilm of bacteria.
A pellicle of salivary glycoproteins adheres to 
the clean tooth and first colonizing Gram-
positive aerobic bacteria attach; the plaque 
biofilm is created. The supragingival plaque 
biofilm matures and influences the develop -
ment of the subgingival biofilm. The 
constituents of the biofilm progress to 
Gram-negative anaerobic, motile, and 
spirochete bacteria. Bacterial byproducts and 
proteolytic enzymes with the host 
inflammatory response cause destruction of 
the periodontium, resulting in the loss of 
attachment for the tooth. The biofilm forms 
within days. Calculus is the mineralization of 
plaque. It is rough, acts a surface area for 
more plaque development, and can be 
mechanically irritating to the tissues.
Gastrointestinal—oral cavity/dentition 
(primary); systemic inflammation/distant 
organ changes.
GENETICS
N/A
Common—estimated to be around 85%.
Worldwide
Species
Toy, brachycephalic, sighthounds, long-facial 
haired, and purebred cats.
Begins as juvenile and progresses through life.
None
SIGNS
Hidden/no clinical signs to halitosis, head 
shyness, oral bleeding, dropping food, 
reluctance to chew, pawing at the mouth, 
exaggerated jaw movements, face rubbing, 
maxillofacial swellings, ptyalism, sneezing, 
and nasal discharge.
• Conscious examination—inflammation of 
the gingiva, plaque and/or calculus, root 
exposure, furcation exposure, mobile teeth, 
parulides, disproportionate plaque and calculus distribution, oral discharge, 
maxillofacial swellings, and mandibular 
lymphadenopathy. The conscious exam -
ination significantly underestimates the 
presence and severity of PD and therefore an 
anesthetized examination with periodontal 
probing and intraoral radiographs is required 
for complete assessment. • Anesthetized 
examination—the degree of severity of 
periodontal disease relates to a single tooth. 
(AVDC) nomenclature: ◦ Normal (PD 
0)—clinically normal; no gingival 
inflammation or periodontitis clinically 
evident. ◦ Stage 1 (PD 1)—gingivitis only 
without attachment loss. The height and 
architecture of the alveolar margin are 
normal. ◦ Stage 2 (PD 2)—early perio -
dontitis; less than 25% of attachment loss,* 
or at most, there is a Stage 1 furcation 
involvement in multirooted teeth. ◦ Stage 3 
(PD 3)—moderate periodontitis; 25–50% of 
attachment loss*, and/or there is a Stage 2 
furcation involvement in multirooted teeth. 
◦ Stage 4 (PD 4)—advanced periodontitis; 
more than 50% of attachment loss* or there 
is a Stage 3 furcation involvement in 
multirooted teeth. Furcation indices 
subjectively measure when the periodontal 
probe extends less than half way between the 
roots (F1), extends greater than half way 
(F2), or through and through from one side 
of the furcation and out the other under the 
crown (F3).
*Periodontal attachment loss is measured by 
probing of the clinical attachment level and 
radiographic determination of the distance of the 
alveolar margin from the tooth’s cementoenamel 
junction relative to the length of the root.
CAUSES
Bacterial plaque biofilm and associated host 
inflammatory response.
Lack of daily preventive home care and 
professional veterinary dental care, signal -
ment, systemic health (e.g., immuno -
suppression from pharmaceuticals or 
metabolic disease), inappropriate chewing 
behavior, malocclusions, crowding of 
dentition, oral foreign bodies.
  DIAGNOSIS
Oral neoplasia, drug-associated gingival 
enlargement (e.g., cyclosporine, amlodipine), 
oral autoimmune inflammatory conditions, 
viral ulcerative gingivitis/mucositis (e.g., 
calicivirus), oral trauma and foreign bodies, 
rare fungal. Clinical history, imaging (i.e., 
intraoral radiographs and/or advanced 
imaging), and histopathology for 
differentiation.CBC/BIOCHEMISTRY/URINALYSIS
Overall systemic/metabolic health status and 
for preparation for anesthesia.
N/A
IMAGING
• Intraoral radiography—required diagnostic 
instrument to assess attachment loss, to 
include marginal bone loss, loss of the lamina 
dura, widening of the periodontal ligament 
space, horizontal and vertical bone loss, 
inflammatory resorption of the tooth root 
surface, furcation bone loss, combined 
patterns of bone loss. Horizontal bone loss is 
a pattern where the cortical and alveolar bone 
surrounding the tooth and adjacent teeth are 
lost at a similar rate; the periodontal pocket is 
above the bone (i.e., suprabony pocket). 
Vertical bone loss is a pattern where there is 
bone loss around a tooth root where the 
adjacent supporting bone remains more 
coronal; the periodontal pocket is within the 
bone (i.e., infra(intra) bony pocket). 
• Osteopermeative patterns mimicking 
neoplasia can be present in severe cases. 
Osteitis secondary to the inflammation may 
result in paradoxical proliferation of bone. 
• Cone-beam CT has been reported to be of 
additional valuable in assessing periodontal 
attachment loss in brachycephalic breeds.
• Periodontal probing—the distance 
between free gingival margin and apical 
extent of the sulcus or pocket; probing 
depths <3 mm in dogs and <1 mm in cats 
are considered normal gingival sulcus; 
variations based on the range of breed sizes 
in dogs. • Measurement of root exposure, 
furcation exposures and tooth mobility are 
recorded. • Clinical probing information 
and intraoral radiographic assessment are 
used to assign periodontal score to each 
tooth (PD0–PD4).
Tissues may be edematous, exhibit gingival 
hyperplasia/enlargement, exocytosis of 
inflammatory cells such as lymphocytes, 
plasma cells, and polymorphonuclear 
leukocytes, abundant colonies of bacterial 
microorganisms, areas of fibrosis, edema, 
and hemorrhage; bone may demonstrate 
infiltration of inflammatory cells, and 
resorption with both osteoclastic and 
osteoblastic activity. Osteomyelitis/osteitis 
can result.
  TREATMENT
• Prevention of PD with daily home care 
and annual preventive cleaning, starting in 
first 1–2 years of life; oral examinations and

1064  Blackwell’s Five-Minute Veterinary Consult  
Pperiodontal treatments before excessive 
attachment loss. • Daily home care 
prevention should begin the first year of 
life. Daily tooth brushing is the best daily 
home care prevention. • Annual or 
semi-annual evaluations and periodontal 
cleanings/“prophylaxis” and treatment based 
on the patient signalment and progressive 
PD stage status. • Client communication 
and education throughout all patient 
life stages.
Acute-on-chronic periodontal abscessation—
nonsteroidal anti-inflammatory medications, 
if not contraindicated; analgesia and 
appropriate antibiotic selection pending 
scheduling for anesthesia, assessment, and 
ACTIVITY
DIET
Dental diets with fiber arrangements and/or 
added dental products added for patients 
without other dietary restrictions, or needs, 
and who have teeth remaining to chew.
Daily home care, the necessity of general 
anesthesia, and the lifelong prevention, 
management, and treatment of PD.
• Remove the plaque biofilm and calculus, 
eliminate periodontal pocket(s), prevent 
further attachment loss, extract hopelessly 
compromised teeth, address contributing 
dental factors, and treat oral/dental pain. 
Individualized general anesthetic manage -
ment. • Periodontal surgery including, but 
not limited to, gingivectomy/gingivoplasty, 
periceutical treatment, closed root planing, 
open root planing, periodontal flaps, 
osseous resective surgery, osseous additive 
surgery including bone augmentation and 
guided tissue regeneration. Plans are based 
on PD stage, tooth/teeth involved, overall 
systemic health of the patient, ability for 
home care, ability to have further follow-up 
treatments and anesthetic procedures, and 
overall financial aspects for the client with 
the goal to have a pain- and infection-free 
oral cavity.  MEDICATIONS
Systemic use of antimicrobials is not indicated 
in the treatment of PD without surgical 
attention to the underlying cause. Clindamycin, 
amoxicillin/clavulanic acid, and doxycycline 
may be chosen to augment periodontal 
surgical treatment. Metronidazole may be 
selected based on clinical findings and patient 
history.
• Immunosuppressive drugs in untreated PD 
can cause acute-on-chronic exacerbations. 
• Chronic use of bisphosphonates should be 
avoided unless the oral cavity and dentition 
have all active infection and inflammation 
treated.
Prolonged/increased dosages of immuno -
suppressive medications may contribute to 
acute on chronic exacerbations.
Oral chlorhexidine and oral fluoride 
inactivate with simultaneous use.
N/A
  FOLLOW-UP
The diagnosed PD stage guides the recheck 
interval; evaluation every 3–12 months.
Daily tooth brushing with pet toothpaste 
mechanically removes the supragingival plaque 
biofilm. Oral 0.1–0.12% chlorhexidine 
products target oral bacteria involved in the 
plaque biofilm. Dental diets, dental chews, 
barriers sealants, dental wipes, dental enzyme 
systems, dental gels, and water additives can 
be a part of a dental home care program based 
on individual patient and client needs. The 
Veterinary Oral Health Council can help 
guide selection of pet dental products.
Due to the multifactorial aspect of PD and 
individual patient response, the expected 
course and prognosis can be variable, but 
predicable with appropriate treatment.
N/A
Progresses with age; Adult-onset periodontitis 
is most common; juvenile and aggressive 
forms of periodontitis occur.
Capnocytophaga  spp. may cause serious 
opportunistic infections in immuno -
suppressed humans; Pasteurella multocida  may 
cause severe infections in humans following 
cat bites. Scientific developments in the study 
of oral microbiomes suggest transmission/
sharing of oral bacteria can occur between 
species.
N/A
SYNONYMS
N/A
• AVDC = American Veterinary Dental 
College.
• PD = periodontal disease.
• https://avdc.org/avdc-nomenclature/
• http://www.vohc.org
Lobprise H, Stepaniuk K. Oral surgery—
periodontal surgery. In: Lobprise H, Dodd 
JR, eds., ‘Wiggs’ Veterinary Dentistry—
Principles and Practice, 2nd ed. Hoboken, 
NJ: Wiley-Blackwell, 2019, pp. 193–228.
Author  Kevin S. Stepaniuk
available onlinePeriodontal Disease  (continued)

Canine and Feline, Seventh Edition  1065
PPeripheral Edema
  BASICS
Edema is focal or diffuse excessive 
accumulation of tissue fluid within the 
interstitium; often at gravitative surfaces, 
whether localized or generalized.
• High capillary hydrostatic pressure. 
• Increased capillary permeability. 
• Lymphatic drainage abnormality. • Low 
plasma colloid osmotic pressure.
• Musculoskeletal. • Skin/exocrine.
GENETICS
• Dominantly inherited primary 
lymphedema has been described in poodles. 
• Lethal congenital edema has been 
documented in bulldogs.
Variable
Pertinent when considering infectious disease 
Species
Primary or congenital lymphedema has been 
reported in bulldogs, poodles, Old English 
sheepdogs, Labradors, and myriad other 
canine breeds as well as cats.
SIGNS
• Allergic or other immune, cardiac, hepatic, 
or other organic disease. • T rauma. 
• Exposure to infectious or toxic (venomous) 
agents such as ticks or other arachnids.
• Unexplained weight gain may be noted 
initially; otherwise, early detection is unlikely. 
• Noninflammatory subcutaneous edema is 
often first recognized at the dependent 
thorax, abdomen, or distal limbs. 
• Inflammatory edema may be noted in 
nondependent foci of the interstitium.
CAUSES
Localized or Single-Limb Edema
• Venous or arterial obstruction  
(e.g., thrombosis or postcaval syndrome). 
• Arteriovenous fistula. • Increased capillary 
permeability. • Focal or multifocal immune, 
infectious, or toxic (chemical or biologic) 
insults (e.g., snake bite or bee sting). 
• T rauma. • Burns. • Lymphatic obstruction. 
• Sterile (juvenile pyoderma) or infectious lymphangitis. • Primary or metastatic 
neoplastic invasion of lymphatic tissue. 
• Congenital aplasia or dysgenesis of the 
lymphatic system.
Regional or Generalized Edema
• Congestive heart failure (CHF). • Cardiac 
tamponade. • Cranial or caudal vena caval 
thrombosis. • Renal failure and hypernatremia 
(salt retention). • Paralysis or prolonged 
recumbency with subsequent failure of the 
venous pump. • Tourniquet effect of a 
bandage. • Increased capillary permeability. 
• Systemic immune, infectious, or toxic 
insults (e.g., sepsis or vasculitis). • Lymphatic 
abnormalities. • Acquired regional traumatic, 
immune, infectious, or neoplastic process. 
• Congenital aplasia or other lymphatic 
dysgenesis. • Low plasma colloid osmotic 
pressure. • Protein-losing disease (e.g., 
nephrotic syndrome or intestinal 
lymphangiectasia). • Failure to produce 
protein (e.g., cirrhosis). • Exudative protein 
loss (e.g., severe burn).
Variable
  DIAGNOSIS
• Peripheral edema secondary to myxedema 
or inflammation is typically non-pitting. 
• Bilateral forelimb edema with jugular 
venous distention implies cranial vena caval 
syndrome. • Bilateral rear limb edema with 
or without ascites implies either hypo -
albuminemia or caudal vena caval 
obstruction. • Fore and/or rear limb edema 
with jugular venous distension, hydrothorax, 
and/or ascites implies cardiac disease. • Focal 
edema with bruit and fremitus implies an 
arteriovenous fistula. • Focal edema with 
erythema may be secondary to an insect or 
other bite. • Multifocal or diffuse edema with 
petechiation and/or ecchymosis may be 
associated with a coagulopathy or vasculitis.
• Leukocytosis suggests inflammatory or 
infectious disease. • Thrombocytopenia may be 
secondary to vasculitis (e.g., Rocky Mountain 
spotted fever [RMSF]), systemic lupus 
erythematosus, or a coagulopathy  
(e.g., disseminated intravascular coagulation 
[DIC]). • Panhypoproteinemia is consistent 
with gastrointestinal disease, but diarrhea  
is not an obligatory clinical sign. 
• Panhypoproteinemia and hypocholesterolemia 
are seen with intestinal lymphangiectasia. 
• Hypoalbuminemia may occur with 
hepatic failure. • Hypoalbuminemia with 
proteinuria suggests glomerular disease. • Hypoalbuminemia with proteinuria and 
hypercholesterolemia in an edematous patient 
defines nephrotic syndrome.
• Antithrombin III assay indicated in 
conditions with albumin loss. • Further 
delineate thrombocytopenia with a bone 
marrow biopsy, antinuclear antibody, screen 
for Ehrlichia  and RMSF , and a coagulation 
profile. • Panhypoproteinemia may dictate a 
need for intestinal biopsy. 
• Hypoalbuminemia may warrant liver 
function testing (e.g., bile acid test, hepatic 
biopsy). • Confirm proteinuria with a urine 
protein:creatinine ratio. • Bacterial and 
fungal cultures of blind fistulae may prove 
useful. • Fungal or other assays of infectious 
disease may be warranted; patient’s primary 
residence and patient’s travel history need to 
be considered. • Pleural or peritoneal fluid 
analysis is suggested, if effusion is present. 
• Low resting thyroid hormone (T4) should 
be elaborated with a thyrotropin-releasing 
hormone stimulation test, free T4 by 
equilibrium dialysis, or thyroid-stimulating 
hormone (TSH) concentration.
IMAGING
• Suspected heart disease necessitates thoracic 
radiographs and/or echocardiogram. 
• Angiography (e.g., venacavagram) may help 
to define a vascular obstruction. • Diagnostic 
ultrasound may help to delineate a vascular 
occlusion. • Thermography and perfusion 
scans (e.g., scintigraphy) are esoteric but have 
been used to diagnose occlusive vascular 
disease.
• Fine-needle aspiration of an affected area 
for cytology and culture may be helpful. 
• Biopsy and deep culture may help define an 
underlying cause for edema.
Depend on cause of the edema.
  TREATMENT
Depends on the cause of the edema and 
stability of the patient.
• Application of warm compresses is 
recommended for patients with edema 
secondary to infection. • Good nursing care 
required to prevent decubital ulceration in 
ACTIVITY
Depends on cause of edema—e.g., exercise 
restriction is recommended in patients with 

1066  Blackwell’s Five-Minute Veterinary Consult  
PDIET
Depends on the cause of edema—e.g., 
patients with protein-losing nephropathy 
require a restricted protein diet.
Depends on the cause of edema.
• Surgery such as lymphangioplasty, 
thrombectomy, or lymphaticovenous shunt 
may be palliative. • Amputation of the 
edematous limb is sometimes indicated. 
• Arteriovenous fistulae may be treated by 
various surgical methods.
• Anaphylaxis—epinephrine (1 mg/mL) at 
0.01 mL/kg IM or SC to a maximum of 
0.02–0.05 mL; prednisone sodium succinate 
10–30 mg/kg IV; antihistamines are of 
equivocal benefit once anaphylaxis ensues. 
• Lymphedema—benzopyrone use yields 
variable results in veterinary medicine; rutin 
50 mg/kg PO q8h has been mixed with food 
for cats with chylothorax. • Cardiogenic 
edema—combinations of positive inotropes, 
vasodilators, and diuretics commonly used 
in patients with CHF . • Immune-mediated 
edema requires immunosuppressive therapy 
(e.g., prednisone). • Vasculitis and edema 
secondary to rickettsial disease typically 
responds to tetracycline 22 mg/kg PO q8h 
or doxycycline 5 mg/kg PO q12h. • Edema 
in association with other infectious agents 
requires antifungal therapy or antibiotic 
therapy. • Myxedema secondary to 
hypothyroidism should respond gradually to 
T4 supplementation. • Edema associated 
with toxic insults may be slowed with 
antidotes (e.g., antivenom). • Anticoagulant 
therapy may benefit patients with DIC or 
antithrombin III deficiency. • Vascular 
volume expanders such as hydroxyethyl 
starch or plasma often benefit patients with 
low plasma oncotic pressure; very-low-dose 
furosemide in a constant-rate infusion of  
0.1 mg/kg/h has been effective in 
conjunction with a volume expander.
• Diuretics generally aggravate edema of 
noncardiogenic origin. • Steroids may 
worsen edema secondary to infectious disease. • Epinephrine—generally 
contraindicated in shock except in 
anaphylaxis. • Propranolol (beta-blocker)—
contraindicated in patients predisposed to 
bronchospasm.
• Avoid intramuscular injections in patients 
with thrombocytopenia. • Taper patients on 
long-term steroid therapy so that endogenous 
steroid production resumes. • Use epinephrine 
cautiously in patients predisposed to 
ventricular fibrillation. • Use enalapril and 
other ACE inhibitors cautiously in patients 
with renal disease. • Long-term antibiotic 
therapy may facilitate a superinfection by a 
fungus (e.g., Candida ) or resistant bacteria. 
• Monitor anticoagulants closely to avoid 
fatal hemorrhage.
  FOLLOW-UP
• Repeat complete blood counts, chemistries, 
and urine protein:creatinine ratios for blood 
dyscrasias and serum and urine protein 
concentrations. • Weekly assessment of 
prothrombin or partial thromboplastin time 
for patients on warfarin or heparin. • Serial 
biopsies of affected tissue such as kidney with 
glomerulonephritis may help to prognosticate. 
• Repeat cultures or acute and convalescing 
titers for patients suffering from an infectious 
disease. • Periodic T4/TSH assay (4–6 hours 
post pill) for patients receiving thyroid 
Depends on the cause of the edema.
• Decubital ulceration. • Fatal hemorrhage. 
• Fatal thrombosis. • Refractory cardiac, 
gastrointestinal, hepatic, or renal failure. 
• Malnutrition. • Cerebral edema and 
herniation. • Resistant infection and sepsis.
Depends on cause of the edema.
Pericardial, pleural, or peritoneal effusion.AGE-RELATED FACTORS
Vascular anomalies or primary lymphedema 
are generally documented in juvenile patients 
(e.g., anasarca).
• Tick exposure is common in pets and their 
owners; both may suffer simultaneously from 
rickettsial disease. • Certain protozoal 
(Leishmania ), fungal ( Sporothrix ), and 
bacterial ( Brucella ) organisms may transfer to 
people via direct contact.
Brucellosis has been associated with vulvar 
edema, necrotizing vasculitis, and embryonic 
death or fetal abortion.
SYNONYMS
Anasarca
SEE ALSO
• Ascites.
• Lymphedema.
• Vasculitis, Systemic (Including Phlebitis).
• RMSF = Rocky Mountain spotted fever.
Lymphedema: clinical signs, diagnosis and 
treatment. J Vet Intern Med 1992, 6:312–319.
Fox PR, Petrie JP , Hohenhaus AE. Peripheral 
vascular disease. In: Ettinger SJ, Feldman EC, 
eds., Textbook of Veterinary Internal Medicine, 
6th ed. St. Louis, MO: Elsevier, 2005.
Jacobsen JO, Eggers C. Primary lymphedema 
in a kitten. J Small Anim Pract 1997, 18–20.
Author  Marc Elie
Consulting Editor  Michael AhernePeripheral Edema  (continued)

Canine and Feline, Seventh Edition  1067
PPerirenal Pseudocysts
  BASICS
OVERVIEW
• Capsulogenic renal cyst, capsular cyst, 
pararenal pseudocyst, capsular hydronephrosis, 
perirenal cyst, and perirenal pseudocyst are 
terms used to describe renomegaly caused by 
accumulation of fluid between the kidney and 
its surrounding capsule. One or both kidneys 
are affected. • The tissue sac in which the 
fluid accumulates is not lined with secretory 
epithelium; and thus the name “pseudo”-cyst 
• Primarily older male cats (>8 years).
• When detected in young cats, the disease is 
usually unilateral. • Rare in dogs; the difference 
in prevalence between species may be related to 
the prominent network of subcapsular veins 
that characterize feline kidneys.
SIGNS
• May be asymptomatic. • Nonpainful, 
enlarged abdomen is common. • Signs of 
concomitant renal failure in some patients.
• Cause of perirenal accumulation of fluid is 
often not understood. • Accumulation of 
pseudocyst fluid is a dynamic, not a static, 
process. • Cytologic and biochemical 
evaluation of pseudocyst fluid may aid 
understanding of pathophysiologic 
mechanisms. • Fluid with characteristics of a 
transudate may accumulate because of high 
capillary hydrostatic pressure or lymphatic 
obstruction. Some cats have light microscopic 
evidence of renal fibrosis. However, it is not 
known whether progressive renal parenchymal 
contraction occludes lymphatics and blood 
vessels, promoting transudation of fluid. 
• Perirenal accumulation of transudate can 
also result from rupture of renal cysts. 
• Accumulation of perirenal urine may 
indicate disruption of the renal pelvis or the 
proximal ureter. • Accumulation of blood in 
pseudocysts can result from external trauma, 
surgery, neoplastic erosion of blood vessels, 
rupture of aneurysms, coagulopathies, or 
paracentesis of the urinary tract.
  DIAGNOSIS
• Causes of renomegaly include renal neoplasia, 
hydronephrosis, polycystic kidney disease 
(common), feline infectious peritonitis, and 
mycotic or bacterial nephritis (less common). 
• Ascites and enlargement of other abdominal 
organs can cause nonpainful distension of the 
abdomen.CBC/BIOCHEMISTRY/URINALYSIS
• Results unremarkable until patient develops 
renal insufficiency. • Azotemia and 
inappropriately low urinary specific gravity 
(<1.035) indicate concomitant chronic 
kidney disease (CKD).
N/A
IMAGING
• Renomegaly is commonly detected by 
abdominal radiography. • Excretory 
urography and ultrasonography can be used 
to determine whether the underlying renal 
parenchyma is normal or abnormal. Small 
kidneys beneath an abnormally wide 
fluid-filled intracapsular space is a common 
finding.
Cytologic examination of pseudocyst fluid 
may provide evidence of the underlying 
disease process resulting in fluid 
accumulation (e.g., transudation, 
hemorrhage, lymphatic obstruction, 
inflammation, urine, etc.) or secondary 
complications (e.g., infection). Creatinine 
concentrations that are higher in 
pseudocyst fluid compared to serum are 
consistent with urinary tract rupture.
  TREATMENT
• Perirenal pseudocysts are not immediately 
life-threatening. • Some patients need no 
treatment. • Many patients require further 
diagnostic evaluation and treatment of 
concomitant CKD. • Capsulectomy or 
pseudocyst fenestration (remove greater 
than 1 cm × 1 cm section of capsule to 
minimize spontaneous closure of the 
fenestration) is generally associated with 
amelioration of abdominal distention and 
abdominal organ displacement. Early stages 
of CKD may resolve; however, progression 
of CKD commonly occurs. • Long-term 
response is unknown. • Avoid nephrectomy 
to maximize remaining kidney function. 
• Decompression by paracentesis with a 
needle and syringe provides temporary 
relief. • If pseudocysts refill with fluid 
(often in 1–2 weeks), paracentesis can then 
be repeated.
Consider appropriate antimicrobic (i.e., 
lipid-soluble antibiotic chosen on the basis of 
antimicrobial susceptibility) if pseudocysts 
become infected.  FOLLOW-UP
• Monitor patients periodically (every 2–6 
months) for development and progression of 
CKD. • Short-term prognosis appears 
favorable with or without pseudocyst 
decompression in patients with no evidence 
of CKD. • Long-term prognosis is unknown 
because it has not been determined whether 
perirenal pseudocysts are associated with 
underlying lesions in the renal parenchyma 
that may be progressive. It is also unknown 
whether perirenal pseudocysts are associated 
with hypertension. • Survival is related to the 
severity and progression of CKD.
Beck JA, Bellenger CR, Lamb WA, et al. 
Perirenal pseudocysts in 26 cats. Aust Vet J 
2000, 78:166–171.
Lulich JP , Osborne CA, Polzin DJ. Cystic 
diseases of the kidney. In: Osborne CA, 
Finco DR, eds., Canine and Feline 
Nephrology and Urology. Philadelphia, PA: 
Williams & Wilkins, 1995, pp. 460–483.
Ochoa VB, DiBartola SP , Chew DJ, et al. 
Perinephric pseudocysts in the cat: a 
retrospective study and review of the 
literature. J Vet Intern Med 1999, 
13:47–55.
Author  Jody P . Lulich
acknowledge the prior contribution of Carl 
A. Osborne.

1068  Blackwell’s Five-Minute Veterinary Consult  
PPeritoneopericardial Diaphragmatic Hernia
  BASICS
OVERVIEW
• Embryologic malformation of the ventral 
midline allowing communication between the 
pericardial and peritoneal cavities.
• May be associated with other congenital 
malformations including sternal deformities 
(especially in cats), cranial abdominal hernia, 
and ventricular septal defects.
• Signs may be due to large amounts of 
abdominal viscera compressing the heart or 
lungs and incarceration of abdominal organs 
(e.g., liver and small bowel). However, many 
affected animals remain asymptomatic.
• Age when clinical signs first occur varies; 
more than one-third of patients are 4 years of 
age or older.
• Weimaraners and Persians may be predisposed.
• No evidence that lesions are hereditary, but 
they have been reported in littermates.
SIGNS
Depend on the nature and amount of 
abdominal contents that are herniated.
• Dyspnea.
• Displaced or attenuated apical cardiac impulse.
• Palpable sternal deformity or cranial 
abdominal hernia.
• Cardiac tamponade and signs of right-sided 
congestive heart failure (rare).
• Embryologic malformation.
• Prenatal injury of the septum transversum 
and pleuroperitoneal folds.
  DIAGNOSIS
• Never an acquired traumatic defect because 
no natural direct communication exists 
between the peritoneal and pericardial cavities 
after birth.
No associated hematologic or biochemical 
alterations.OTHER LABORATORY TESTS
N/A
IMAGING
• Radiographic findings depend on size of 
defect and amount of herniated abdominal 
contents; caudal heart border and diaphragm 
usually overlap; thoracic radiographs may 
show an “empty” abdomen and possible 
multiple radiographic densities within the 
cardiac silhouette.
• Positive and negative contrast 
peritoneography have been used to evaluate 
the diaphragm. Injection of 1–2 mL/kg body 
weight of water-soluble positive contrast into 
the peritoneal cavity followed by right and 
left lateral, sternal, and dorsal recumbent 
radiographs allows complete evaluation of the 
diaphragm. Identification of contrast within 
the pleural space confirms the diagnosis of 
diaphragmatic rupture. Air, carbon dioxide, 
or nitrous oxide may also be used.
• Barium series may demonstrate bowel loops 
crossing the diaphragm and within the 
pericardial sac.
• Nonselective angiography outlines the 
cardiac chambers within the large cardiac 
silhouette.
• Echocardiography gives a definitive 
Electrocardiogram may show small complexes 
if abdominal contents have herniated or if 
marked effusion is present.
  TREATMENT
Surgical closure of the hernia after 
returning viable organs to their normal 
location is usually curative. In 
asymptomatic adult patients, treatment 
may not be indicated.
• Myocardial contractility is unaffected in 
most patients; drugs for improving cardiac 
output are not indicated.
• Can give symptomatic treatment based on 
nature and amount of abdominal contents 
that are herniated.
Drugs that reduce ventricular afterload (e.g., 
arteriolar vasodilators) or preload (e.g., 
venous dilators and diuretics) are not useful 
and can cause reduction of ventricular filling, 
hypotension, and low cardiac output.  FOLLOW-UP
Prognosis after surgery is excellent in animals 
with no other significant congenital 
anomalies or complicating factors. Some 
affected animals remain asymptomatic 
throughout life.
Burns CG, Bergh MS, McLouhlin, MA. 
in dogs and cats: 58 cases (1999–2008). 
J Am Vet Med Assoc 2011, 22:643–650.
FWK, Tilley LP , Oyama M, Sleeper M, 
Kienle RD. Pericardial disease and cardiac 
neoplasia. In: Kittleson MD, Kienle RD, 
eds., Small Animal Cardiovascular 
Medicine. St. Louis, MO: Mosby, 1999, 
pp. 413–432.
Neiger R. Peritoneopericardial diaphragmatic 
hernia in cats. Compend Contin Educ Pract 
Vet 1996, 461–479.
Reimer SB, Kyles AE, Filipowicz DE, et al. 
Long-term outcome of cats treated 
conservatively or surgically for 
peritoneopericardial diaphragmatic hernia: 
66 cases (1987–2002). J Am Vet Med Assoc 
2004, 224:728–732.

Canine and Feline, Seventh Edition  1069
PPeritonitis
  BASICS
Inflammatory process involving the serous 
membrane of the abdominal cavity.
• Insult to the peritoneal cavity (localized or 
generalized) leads to inflammation 
characterized by vasodilation, cellular 
infiltration, pain, and development of 
adhesions. Fluid production is eventually 
favored over absorption, and progresses from 
transudate to exudate. • Extent and severity 
depend on type and severity of insult.
• Response to bacterial peritonitis associated 
with lipopolysaccharide (LPS; Gram-negative 
bacteria) or peptidoglycans (Gram-positive 
bacteria), causing inflammatory cytokine and 
nitric oxide (NO) production. NO causes 
vasodilation, can lead to hypotension. 
• Inflammation causes vasodilation and 
increased vascular permeability. Cytokine 
release from leukocytes results in chemotaxis 
and activation of complement. Activation of 
complement results in coagulation, fibrin 
production and decreased fibrinolysis, 
resulting in adhesion formation. • Result of 
significant abdominal inflammation can be 
(SIRS) and sepsis. SIRS can progress to 
multiple organ dysfunction (MODS) and 
affect respiratory system (acute respiratory 
distress syndrome or pulmonary 
thromboembolism), or cause renal 
dysfunction, reduced cardiac function, and 
neurologic dysfunction.
• Cardiovascular. • Gastrointestinal (GI). 
• Hemic/lymphatic/immune. • Renal/
urologic hepatobiliary.
GENETICS
N/A
N/A
N/A
Species
None
None
NoneSIGNS
Signs may be vague and nonspecific and 
depend on timeline of evaluation in relation 
to inflammation and systemic response.
Lethargy, depression, anorexia, vomiting 
(common), diarrhea, collapse.
• Abdominal discomfort or pain—localized 
or generalized. • Shock: ◦ Compensatory—
tachycardia, tachypnea, injected mucus 
membranes, rapid capillary refill time (CRT). 
◦ Early decompensatory—tachycardia, poor 
pulse quality, depressed mentation, pallor, 
prolonged CRT. Cats may show a normal to 
decreased heart rate (<140/min). 
◦ Decompensatory—bradycardia, weak or 
absent pulses, severely depressed mentation, 
pallor or cyanosis, prolonged CRT. 
• Arrhythmias/pulse deficits may be detected. 
• Fever. • Weight loss—reported in 1/3 of 
dogs and cats with secondary peritonitis. 
• SIRS—tachycardia (dog >140/min, cat 
>240/min) or bradycardia (cat <130/min); 
tachypnea (dog >30/min, cat >40/min), 
hyperthermia (dog >102.5°F [39.1°C], cat 
>104.5°F [40.3°C]) or hypothermia (dog or 
cat <100°F [37.7°C]), leukocytosis (dog 
>19,000/ μL, cat >18,000/ μL), or leukopenia 
(dog <6000/ μL, cat <5000/ μL).
CAUSES
Primary Peritonitis
• Uncommon, no identifiable intraperitoneal 
source. More common in cats (14%). • May be 
monomicrobial, Gram-positive in 80% of dogs, 
60% of cats. • Results from hematogenous or 
lymphatic spread or translocation from GI 
tract; may spread from oviduct. • Feline 
infectious peritonitis (FIP) in cats.
Secondary Peritonitis
• Most common. • Contamination of 
peritoneal cavity from abdominal organ: ◦ GI 
source (up to 75%) from perforation 
(ulcerations, neoplasia, ischemia), leakage 
following GI surgery, penetrating trauma, 
biliary tract rupture (obstruction, trauma, 
mucocele), or pancreatitis. ◦ Abscessation 
(liver, pancreas, kidney, prostate, lymph 
nodes, spleen). ◦ Urogenital source 
(pyometra, urine leakage). ◦ Uroabdomen 
and bile peritonitis may or may not be septic; 
regardless, chemical peritonitis is present.
• T rauma. • Foreign body ingestion. • Biliary 
mucocele. • GI surgery. • Nonsteroidal 
anti-inflammatory drug (NSAID) use 
associated with GI perforation.  DIAGNOSIS
Other causes of abdominal pain or distention, 
sepsis, and shock.
• Neutrophilic leukocytosis common; 
possible left shift; degenerative left shift, or 
development of neutropenia may portend 
worsening prognosis. • Hemoconcentration 
or anemia. • Hypoproteinemia. • Hypo- or 
hyperkalemia; hyponatremia (fluid loss into 
peritoneum). • Azotemia—prerenal, renal, or 
post renal. • Metabolic acidosis. • Hypogly -
cemia—may indicate sepsis; hyperglycemia 
may be present in cats. • Liver enzyme 
activity elevations—hepatic causes of 
peritonitis or MODS. • Hyperlactatemia—
poor tissue oxygen delivery.
Coagulation testing—disseminated 
intravascular coagulation (DIC): prolonged 
activated partial thromboplastin time (aPTT) 
and thrombocytopenia initially, progress to 
prolonged prothrombin time (PT), aPTT, 
elevated D-dimers (>1,000 ng/mL).
IMAGING
• Findings depend on cause; make right and 
left lateral projections of abdomen. • Loss of 
serosal detail (ground-glass appearance 
suggests fluid in abdominal cavity)—rule out 
lack of intra-abdominal fat (cachexia, 
neonates). • Generalized ileus. • Pneumo -
peritoneum—gas in abdomen may be slight, 
closely evaluate region near diaphragm; 
consider making lateral beam images with 
patient in a sternal or lateral recumbency. 
• Can be diagnostic for gastric dilatation/
volvulus, GI foreign bodies, mass lesions, 
organs enlargement (neoplasia, abscess). 
• Contrast procedures—rarely warranted; 
may complicate management if contrast 
material enters abdominal cavity; avoid 
barium if GI perforation suspected.
Ultrasound
Identify (and aspirate) small volumes of 
peritoneal effusion, abscesses, gallbladder 
rupture or mucocele, tumors, obstructions, or 
mass lesions.
• Abdominocentesis and diagnostic peritoneal 
lavage—perform as soon as possible:  
(1) Cytology—collect aliquot of sample into 
EDTA tube; note color and clarity and 
presence of fibrin. (2) Place second aliquot into 
red-top tube for biochemical testing if needed, 
based on suspected etiology. Chemical

1070  Blackwell’s Five-Minute Veterinary Consult  
Pperitonitis—analyze abdominal fluid for 
creatinine (for uroabdomen), specific pancreatic 
lipase (for pancreatitis), and bilirubin (for bile 
leakage). (3) Culture and sensitivity—next, 
aseptically place an aliquot of sample in a 
sterile-white top (no additive) tube. • Suspect 
FIP—submit abdominal fluid for protein 
electrophoresis and globulin determination.
• Intracellular bacteria, degenerative 
neutrophils, and plant material are diagnostic 
of septic peritonitis. • Normal peritoneal 
fluid contains <2,500 cells/ μL. • Glucose 
concentration in abdominal fluid more than 
20 mg/dL less than peripheral blood glucose 
concentration suggests septic peritonitis. 
• Peritoneal lactate >4.2 mmol/L suggests 
peritonitis in dogs. • Recent surgery results in 
<10,000 cells/mL; primary peritonitis usually 
results in 7,000 cells/ μL in dogs and 3,000 
cells/μL in cats. • Fluid bilirubin or 
creatinine levels at least two times higher than 
that of peripheral blood indicate bile 
peritonitis or uroabdomen, respectively. 
Acellular homogenous, laminated, basophilic 
material on cytology may be mucoid material 
associated with bile peritonitis.
  TREATMENT
• Inpatient—intensive monitoring and 
supportive care are required. • Goals—blood 
pressure >90 mmHg (measured by Doppler), 
heart rate 80–140/min (dogs) and 160–225/min 
(cats), CRT 1.5–2 seconds, urine output 
>1–2 mL/kg/h, blood lactate <2.5 mmol/L. 
Blood lactate concentration should improve 
with resuscitation; inability to do so suggests 
poorer prognosis.
IV Fluid Therapy
• Critical for correction of hemodynamic 
disturbances, electrolyte and acid–base 
abnormalities prior to surgery. • Balanced 
isotonic replacement crystalloid solution—
evaluate response to therapy frequently: 
◦ Rate—may initially require multiple 
boluses of 10–30 mL/kg (depending on other 
patient parameters); reevaluate patient 
frequently, adjust fluid rate or repeat boluses 
as patient status changes. • Potassium and 
glucose supplementation as necessary: ◦ Rate 
of potassium supplementation should not 
exceed 0.5 mEq/kg/h of potassium. 
• Synthetic colloids sometimes utilized (up to 
20 mL/kg/d); concerns for acute kidney 
injury have decreased usage, especially in 
patients with sepsis. • Canine albumin 
transfusion indicated for severe 
hypoalbuminemia (<1.2 mg/dL). • Whole 
blood or packed red blood cells—as required for anemia. • Inadequate response to therapy 
may prompt vasopressor administration 
(norepinephrine, vasopressin, dopamine). 
Norepinephrine is recommended for animals 
with sepsis. • DIC—remove inciting cause, 
support coagulation with fresh frozen plasma 
• Significant; dependent upon severity of 
systemic signs.
• IV fluid therapy and maintenance of tissue 
ACTIVITY
Decreased; depends on inciting cause and 
DIET
• Dictated by cause and concurrent 
conditions (e.g., heart disease). • Feeding 
tube placement should be considered and 
placed at time of surgery for early nutritional 
support (e.g., esophagostomy, gastrostomy, 
jejunostomy). Nasogastric tube for feeding 
and gastric decompression if necessary. 
• Adequate nutrition—essential to optimize 
outcome, attenuate hypermetabolic state, 
preserve hepatic antioxidant defenses, prevent 
protein-calorie malnutrition, maintain GI 
barrier function.
• Advise client of high rate of morbidity and 
(especially septic peritonitis) mortality. 
• Extensive monitoring and intensive care 
may be costly, with prolonged hospitalization.
• Decision to treat medically or surgically—
dictated by etiology, patient’s response to 
initial treatment, and owner’s financial 
constraints. • Known bacterial contamination 
or suspected chemical peritonitis—surgical 
intervention necessary. • Perform surgery as 
soon as patient is stable. Prompt source 
control allows deescalation of antibosis, which 
may only be required for 4–8 days. 
• Exploratory laparotomy—prepare for 
incision extending from xiphoid to pubis; 
goals of surgery are to remove source of 
contamination, debride and lavage abdomen, 
collect fluid or tissue for Gram stain and 
aerobic and anaerobic culture, and provide 
access for nutritional support; use mono -
filament absorbable or nonabsorbable suture 
within abdomen; before closing, thoroughly 
lavage abdomen with 200–300 mL/kg warm 
sterile saline. Do not add antimicrobials or 
other products to lavage solution; remove all 
lavage solution from abdomen. • Surgeon 
must assess organ viability and perform 
resections if necessary. Anastomosis of GI tract 
should utilize healthy tissue; consider serosal 
patching, perform omental patching if serosal 
patching not done. Stapled anastomoses may 
have a decreased risk of dehiscence in septic peritonitis. • Consider omentalization of 
pancreatic abscesses, perform omentalization 
for prostatic abscessation. Remove affected 
organ or part in other cases of abscessation 
(liver lobectomy, nephrectomy). • Consider 
abdominal drainage—based on degree of 
contamination, ability to debride abdomen, 
severity of illness, and anticipation of septic 
complications: ◦ Allows continued removal of 
fluid, bacteria, and toxins. ◦ Forms include 
closed suction drains, vacuum-assisted 
peritoneal drainage (VAPD), and closure of 
caudal abdomen with partial closure of cranial 
abdomen. Sterile bandaging is required in 
each form; less external materials for VAPD, 
but regulate suction and specialized foam and 
connections to suction required. ◦ Requires 
anesthesia for abdominal closure unless closed 
suction drains are used. Severe peritonitis may 
require repeated exploration, debridement, 
and lavage prior to closure.
• Antimicrobials—early and aggressive 
broad-spectrum therapy for suspected septic 
peritonitis; final therapy based on culture and 
susceptibility testing. • Initial therapy—
Gram-negative (enrofloxacin, cefotaxime, 
amikacin); Gram-positive (ampicillin, 
clindamycin); anaerobes (metronidazole): 
◦ Ampicillin 22 mg/kg IV q6–8h. 
◦ Ampicillin/sulbactam 25–30 mg/kg IV 
q6–8h. ◦ Clindamycin 12 mg/kg IV q12h. 
◦ Cefotaxime 20–80 mg/kg IV q8h. 
◦ Enrofloxacin 10–20 mg/kg IV q24h (dogs); 
5 mg/kg IV q24h (cats). ◦ Amikacin 15  
mg/kg IV q24h. ◦ Metronidazole 10 mg/kg 
IV q12h. ◦ Analgesia—depends on pain 
severity; may be intermittent or via CRI; 
opioids recommended: ◦ Multimodal IV 
combinations for pain; dogs, morphine 
0.05–0.2 mg/kg/h or fentanyl 2–5 μg/kg/h, 
ketamine 0.2–0.5 mg/kg/h, lidocaine  
2–4 mg/kg/h; cats, fentanyl 2–5 μg/kg/h, 
ketamine 0.05–0.2 mg/kg/h. Lidocaine may 
improve outcome following surgery in dogs. 
• GI protectants— if GI ulceration: 
◦ Famotidine 0.5–1.0 mg/kg IV q12h. 
◦ Pantoprazole 1 mg/kg IV q12–24h 
(more effective acid reduction). ◦ Sucralfate: 
dogs, 0.5–1.0 mg PO q8h; cats, 0.25–0.5 mg 
PO q8h.
• Glucocorticoids—physiologic dose  
(0.5 mg/kg prednisone equivalent) may be 
indicated for hypotension unresponsive to 
fluids and pressors. • NSAIDs are not 
recommended due to risk of acute kidney 
injury and GI ulceration in poorly 
perfused patients.Peritonitis  (continued)

Canine and Feline, Seventh Edition  1071
PPRECAUTIONS
• Aminoglycosides—use with caution if 
hypotensive, dehydrated, impaired renal 
function. • Adequate hydration—essential to 
enhance safety of these drugs.
Sucralfate works best at low pH; admini -
stration should be staggered with GI acid 
reducers, if both used. Avoid giving oral 
medications at same time as sucralfate.
Fluoroquinolone—enrofloxacin or 
orbifloxacin; substitute for an aminoglycoside, 
especially with impaired renal function.
  FOLLOW-UP
• Fluid balance, electrolyte balance, acid–base 
status, blood lactate—as necessary depending 
on severity of condition. • Frequency of 
monitoring—varies with condition and 
response to treatment; generally q2h. • Urine 
output—target 1–2 mL/kg/h. • Quantify and 
replace fluid losses (vomiting, diarrhea). 
• Change recumbency q4–6h. • Enteral 
nutrition as soon as possible via oral or tube 
feeding: promotes enterocyte health and 
decreases bacterial translocation. Does not 
increase risk of complications. • Repeat 
ultrasound and abdominal fluid cytologic 
evaluation depending on index of suspicion 
for leakage of intestinal surgery sites. • CBC, 
chemistry profile, urinalysis—every 1–2 days 
during periods of intensive monitoring, even 
in patients that are responding. • Coagulation 
testing q24–48h.
Prevention—difficult except with specific risk 
factors (e.g., pyometra, prostatic abscess can 
be avoided with sterilization).
• If underlying cause is not identified and 
managed, patient is at risk for complications. 
• Open peritoneal drainage—increased cost 
and required intensive care, repeated sedation or anesthesia for aseptic bandage changes, 
nosocomial infection, hypoproteinemia, 
electrolyte imbalances, enterocutaneous 
fistulation, and abdominal hernia formation. 
• Adhesions, granuloma formation with 
barium peritonitis.
• Prognosis—depends on rapid identification 
and successful management of underlying 
cause and appropriate follow-up care. • Septic 
peritonitis—mortality of 30–68%. Prognosis 
worse in animals with preexisting septic 
peritonitis, uncorrectable hypotension, low 
serum albumin and total protein concentra -
tions, respiratory dysfunction, DIC, low 
concentrations of protein C, or antithrombin, 
MODS; better survival in patients with lower 
preoperative alanine aminotransferase, 
gamma-glutamyltransferase, packed cell 
volume, total solids, and albumin 
concentration. Open peritoneal drainage may 
improve survival. • Septic bile peritonitis— 
27% survival compared to 100% with 
nonseptic bile peritonitis. • Antibiotic 
treatment within first hour in cases of 
suspected septic peritonitis may significantly 
reduce mortality. • Blood lactate >2.5 
mmol/L or inability to normalize plasma 
lactate—poorer survival. • Feeding tube 
complications depend on site of placement—
esophagostomy (localized infection or 
abscessation); gastrostomy and jejunostomy 
(leakage or premature dislodgement 
associated peritonitis): nasoesophageal or 
nasogastric (sneezing, epistaxis). Refeeding 
syndrome—decreased magnesium, phosphorus, 
potassium; relatively rare but warrants close 
monitoring. • Bradycardia and hypothermia 
in cats with primary septic peritonitis 
associated with mortality.
N/A
N/A
N/A
SEE ALSO
• aPTT = activated partial thromboplastin 
time.
• LPS = lipopolysaccharide.
• MODS = multiple organ dysfunction.
• NO = nitric oxide.
drug.
syndrome.
• VAPD = vacuum-assisted peritoneal drainage.
Cortellini S, Seth M, Kellett-Gregory LM. 
Plasma lactate concentrations in septic 
peritonitis: a retrospective study of 83 dogs 
(2007–2012). J Vet Emerg Crit Care 2015, 
25:388–395.
Dickinson AE, Summers JF , Wignal J, et al. 
Impact of appropriate empirical 
antimicrobial therapy on outcome of dogs 
with septic peritonitis. J Vet Emerg Crit 
Care 2015, 25:152–259.
Grimes JA, Schmiedt CW, Cornell KK, 
Radlinsky MA. Identification of risk factors 
for septic peritonitis and failure to survive 
following gastrointestinal surgery in dogs. 
J Am Vet Med Assoc 2011, 238:486–494.
Hoffberg J, Koenigshof A. Evaluation of the 
safety of early compared to later enteral 
nutrition in canine septic peritonitis. J Am 
Anim Hosp Assoc 2017, 53:90–105.
Author  MaryAnn G. Radlinsky
available online(continued)  Peritonitis

1072  Blackwell’s Five-Minute Veterinary Consult  
PPetechiae, Ecchymosis, Bruising
  BASICS
Pinpoint (petechia) or larger (ecchymosis) 
hemorrhage in the skin or mucous 
membranes most often secondary to 
abnormal primary hemostasis (platelet or 
vessel wall-mediated); may appear 
spontaneously or following trauma. Spontan -
eous development often occurs at sites of 
increased capillary trauma.
• Thrombocytopenia results in impaired 
primary hemostasis and decreased production 
of platelet-derived trophic factors that 
maintain endothelial cell junction integrity.
• Platelet numbers below 50 × 103/μL and 
more often below 25 × 103/μL are associated 
with an increased risk of spontaneous 
• Thrombocytopathies are not generally 
associated with the development of petechiae. 
Some animals with von Willebrand disease 
(VWD) may develop petechiae.
• Vascular hemostatic defects—generally 
caused by systemic disease causing increased 
capillary permeability, vasculitis, or altered 
dermal vascular support (e.g., collagen 
alterations).
• Gastrointestinal—melena/hematochezia/
• Hemic/lymphatic/immune—anemia from 
bleeding.
• Neurologic—variable depending on 
location of bleeding.
• Ophthalmic—scleral/retinal hemorrhage, 
hyphema, secondary glaucoma, and uveitis.
• Renal/urologic—hematuria.
• Respiratory—epistaxis/hemoptysis.
• Skin/exocrine—petechia/ecchymosis/
bruising.
GENETICS
Most etiologies are acquired; immune-
mediated thrombocytopenia (ITP) has a 
possible genetic predisposition in cocker 
spaniels, poodles, Maltese, and Old English 
sheepdogs. Genetic associations exist for 
many thrombocytopathies. VWD is seen in 
Doberman pinschers, German shorthaired 
pointers, Shetland sheepdogs, Scottish 
terriers, and Chesapeake Bay retrievers.
INCIDENCE/PREVELENCE
Common in dogs. Uncommon in cats.
Applicable if associated with a vector-borne 
disease.
• Middle-aged female dogs are at increased 
risk.
• Cats—primary ITP is rare.CAUSES
• Thrombocytopenia—due to platelet 
consumption, destruction, or sequestration
• Vasculitis—secondary to inflammation, 
infection (e.g., Rickettsia rickettsia , sepsis), 
(NSAID) use.
• Geography/travel history (susceptibility to 
tick-borne disease).
• Certain drug exposures (e.g., sulfa-containing 
antimicrobials).
  DIAGNOSIS
Some inflammatory skin lesions may look like 
petechiae. Vasculitis lesions may have 
associated edema. T rauma may cause 
ecchymoses/bruising.
• Red blood cell fragmentation (schistocytosis) 
is associated with disseminated intravascular 
coagulation or microangiopathies.
• Ehrlichia  morulae or other hemoparasites 
may be seen on a peripheral blood smear.
• Patients with myeloproliferative or lympho -
proliferative disease, myelofibrosis, or a 
history of chemotherapy or administration of 
drugs such as estrogens may be concurrently 
leukopenic or have other cytopenias. 
Excessive blood loss will result in anemia.
• Urinalysis (free catch or catheter sample 
instead of cystocentesis if animal may be 
coagulopathic)—may identify hematuria.
• Coagulation studies (activated partial 
thromboplastin time [aPTT], prothrombin 
time [PT], D-dimer, antithrombin 
activity).
• von Willebrand’s factor antigen assay.
• Platelet function tests (e.g., buccal mucosal 
bleeding time [BMBT], PFA-100) are 
inaccurate with thrombocytopenia, but may 
be necessary to rule out platelet function 
disorders, especially if platelet count is normal 
in animals with petechiae.
• Feline leukemia virus (FeLV)/feline 
immunodeficiency virus (FIV) testing—
underlying cause of thrombocytopenia.
• Serology—to diagnose ehrlichiosis, 
Anaplasma platys , Bartonella vinsonii , or RMSF .
• PCR—for possible infections such as 
Ehrlichia  spp., Anaplasma platys  or Babesia  spp., 
Mycoplasma  spp.
IMAGING
Thoracic and abdominal radiography or 
abdominal ultrasonography may help to identify 
neoplasia, pulmonary or other hemorrhage, 
abnormal splenic or lymph node architecture.DIAGNOSTIC PROCEDURES
• Animals with pancytopenia may benefit 
from bone marrow aspirate or biopsy.
• Invasive diagnostic or therapeutic procedures 
may be performed with less risk if platelet 
concentrate or fresh whole blood can be 
administered before or during the procedure.
  TREATMENT
• Minimize activity to reduce the risk of trauma.
• Discontinue any medications that may alter 
platelet function (e.g., NSAIDs).
• Discontinue medications that might be 
associated with ITP .
• Avoid jugular venipuncture.
• Fresh whole blood, platelet-rich plasma, or 
platelet concentrate transfusions may be 
necessary before a definitive diagnosis is made. 
Blood samples for diagnostic testing should be 
collected prior to transfusion if possible.
• Desmopressin acetate (DDAVP) may be an 
effective therapy to control bleeding in 
patients with VWD or NSAID-associated 
thrombocytopathia.
• Acquired thrombopathias and vascular 
disorders should have the underlying disease 
corrected.
Depends on the underlying diagnosis; see 
specific chapters.
Avoid IM injectable medications whenever 
possible.
Avoid NSAIDs and other drugs that inhibit 
  FOLLOW-UP
Serial platelet count for patients with 
thrombocytopenia until an adequate response 
to therapy is seen.
• Death or morbidity caused by hemorrhage 
into critical organs.
• Shock caused by hemorrhagic shock.
• Blindness secondary to sequelae of hyphema.
SYNONYMS
• Bleeding.
• Hemorrhagic diatheses.

Canine and Feline, Seventh Edition  1073
PSEE ALSO
Immune-Mediated.
time.
anemia.
• ITP = immune-mediated 
thrombocytopenia.• NSAID = nonsteroidal anti-inflammatory 
drug.
• VWD = von Willebrand disease.
Blois S. Petechiae and ecchymoses. In: 
Saunders, 2017, pp. 217–219.
Brooks M, Catalfamo JL. Immune-mediated 
thrombocytopenia, von Willebrand disease, 
and platelet disorders. In: Ettinger SJ, ed., 
7th ed. Philadelphia, PA: Saunders, 2010, 
pp. 772–783.
Brooks M, Catalfamo JL. Platelet dysfunc-
tion. In: Bonagura JD, T wedt DC, eds., 
Kirk’s Current Veterinary Therapy XIV: 
Small Animal Practice. Philadelphia, PA: 
Saunders, 2009, pp. 292–297.Neel JA, Birkenheuer AJ, Grindem CB. 
Infectious and immune-mediated 
thrombocytopenia. In: Bonagura JD, T wedt 
DC, eds., Kirk’s Current Veterinary Therapy 
XIV: Small Animal Practice. Philadelphia, 
PA: Saunders, 2009, pp. 281–287.
Russell KE, Grindem CB. Secondary 
thrombocytopenia. In: Feldman BF , Zinki 
JG, Jain NC, eds., Schalm’s Veterinary 
Hematology. Philadelphia, PA: Lippincott 
Williams & Wilkins, 2000, pp. 469–477.
Authors  Justin Farris and Benjamin M. 
Brainard
available online(continued)  Petechiae, Ecchymosis, Bruising

1074  Blackwell’s Five-Minute Veterinary Consult  
P
Petroleum Hydrocarbon Toxicosis
  BASICS
• Petroleum hydrocarbons are a diverse group 
of products derived or synthesized from crude 
oil.
• Certain nonpetroleum-origin hydrocarbons, 
such as turpentine and linseed oil, are toxico -
logically similar enough to be considered 
with petroleum-origin products of similar 
molecular weight. Halogenated hydrocarbons, 
such as carbon tetrachloride or methylene 
chloride, are sufficiently unique to warrant 
separate consideration.
• Small animal poisoning most commonly 
results from exposure to refined commercial 
products including such disparate mixtures as 
fuels, solvents, lubricants, and waxes.
• Petroleum-based solvents are often used as 
“inert” carriers for other potential toxicants 
(e.g., pesticides, paints, medications).
• Most petroleum hydrocarbons can be 
“lumped” into a relatively few broad categories 
based on volatility, viscosity, and surface 
tension. Mixtures with high boiling points 
(low volatility), such as asphalt, mineral oil, 
and waxes, are relatively nontoxic. Products 
with relatively low boiling points and low 
viscosities, such as benzene or turpentine, are 
more readily aspirated, penetrate further into 
airways, and are more likely to cause chemical 
pneumonitis. In general, products that are 
more volatile also tend to be more lipophilic 
and more readily absorbed systemically. 
Products with high aromatic content are also 
predisposed to cause systemic toxicity.
• In general, the most acutely  life-threatening 
effects of hydrocarbon ingestion result from 
aspiration-induced pneumonitis.
• Viscosity and surface tension are reliable 
determinants of pneumotoxic potential. Low 
viscosity permits hydrocarbons to penetrate 
further into smaller airways. Low surface 
tension increases their tendency to “wet” 
pulmonary surfaces. For example, aspiration 
of as little as 0.1 mL of a low-viscosity 
hydrocarbon (e.g., hexane) may produce 
severe pneumonitis, whereas a high-viscosity 
product (e.g., motor oil) would not penetrate 
past the major airways.
• Inhalation of hydrocarbon vapors (as 
opposed to aspirating liquid) may compromise 
pulmonary immune function and displace 
oxygen.
• Topical exposure to hydrocarbon-based 
solvents (e.g., petroleum distillates, 
turpentine) may result in irritation and 
necrosis of skin and cornea.
• Systemic toxicity is possible after oral or 
topical exposure. Although there are no 
quantitative data readily applicable to small 
animals, systemic toxicity should be considered when evaluating pets that have received a 
heavy topical exposure if the hydrocarbon is 
aromatic (e.g., benzene) or a low molecular 
weight (e.g., hexane). Topical exposure is 
especially important in very small animals 
(e.g., puppies, kittens, rodents), which have a 
relatively high body surface area to mass ratio. 
Systemic uptake and thus toxicity are also 
enhanced by factors such as a long hair coat, 
which traps the product against the skin.
• Cardiac.
• Nervous.
• Skin.
• Hematopoietic.
In the author’s experience, the incidence of 
small animal poisonings has decreased in 
recent years.
Species
SIGNS
• Pneumonitis is the most serious 
complication associated with ingestion of 
more volatile (e.g., gasoline) hydrocarbons. 
Respiratory signs usually occur within a few 
minutes to 1–2 hours post ingestion. The 
central nervous and gastrointestinal systems 
may also be affected; death usually results 
from respiratory failure.
• If aspiration occurs simultaneously with 
ingestion, choking, coughing, gagging, and 
varying degrees of dyspnea will occur. Direct 
damage of airway components and bronch -
ospasm may result in hypoxia. Cyanosis may 
develop immediately as alveolar oxygen is 
displaced by hydrocarbon vapor.
• There is some evidence that some hydro -
carbons sensitize the myocardium to both 
endogenous and exogenous catecholamines, 
precipitating arrhythmias; hemolytic anemia 
has been occasionally reported in children.
• A history of (possible) exposure is essential 
to the diagnosis of hydrocarbon intoxication. 
Signs of hydrocarbon poisoning are seldom 
sufficiently characteristic to permit diagnosis.
• Respiratory involvement, when present, is 
usually progressive over the first 24–48 hours, 
then gradually resolves 3–10 days following 
exposure. Animals that remain completely 
asymptomatic for 6–12 hours after ingestion 
are unlikely to develop respiratory illness.
• Characteristic hydrocarbon odor on the 
animal’s breath or coat.
• Animals appear to experience a burning 
sensation in the mouth and pharynx after ingesting hydrocarbons, evidenced by 
slobbering, champing the jaws, shaking the 
head, and pawing at the muzzle.
• Fever in 3–4 hours following aspiration; 
may occur in less than an hour or as much as 
24 hours.
• Vomiting, colic, and diarrhea after oral 
exposure. The severity and presence of such 
signs are a function of the dose and the 
individual hydrocarbon. Heavy aliphatic 
hydrocarbons (e.g., mineral oil) may produce 
mild diarrhea but little else. Lighter hydro -
carbons (e.g., gasoline) are more likely to 
produce colic and vomiting.
• Intoxicated animals may exhibit vertigo, 
ataxia, and mental confusion. Hydrocarbons 
produce depression and narcosis in most 
cases, but tremors and convulsions have also 
been reported in a few cases. If the dose is 
very high, the animal may become comatose 
and die prior to exhibiting signs of 
pneumonitis, although this is very rare.
• Arrhythmias and syncope may occur as a 
result of myocardial sensitization to 
endogenous catecholamines. Myocardial 
sensitization may persist for 24–48 hours 
after apparent recovery from the neurologic 
effects of intoxication.
CAUSES
• Storage in inappropriate containers and 
failure to clean up spills.
• Folk remedies using gasoline, kerosene, and 
other solvents as tonics or vermifuges.
• Use of gasoline or other solvents to remove 
sticky material from an animal’s coat. Cats 
may ingest significant amounts of gasoline or 
other hydrocarbons by grooming themselves 
after topical contamination.
  DIAGNOSIS
• Infectious diseases, toxins, and/or injuries 
may result in respiratory signs like hydro -
carbon aspiration, but only very acute 
processes (e.g., trauma, chylothorax) exhibit a 
similar rapid onset.
• Acute ethylene glycol, ethanol, or drug 
• Urine and serum will be negative for ethylene 
glycol; serum osmolality will be normal.
• CBC may indicate stress, but this usually 
does not occur early in the process.
• A simple spot test involves mixing vomitus 
or gastric contents vigorously with warm 
water. Gasoline or other petroleum distillates 
will float to the surface. Care must be taken 
to distinguish between petroleum products 
and dietary lipids. The former usually have a 
characteristic odor.

Canine and Feline, Seventh Edition  1075
P
• Most petroleum products lighter than 
kerosene, if isolated and absorbed onto a 
paper towel, evaporate relatively quickly with 
little residue and have a characteristic odor.
• Chemical analysis of ingesta or post-
mortem tissues is useful forensically but is not 
practical for clinical evaluation. If chemical 
analysis is conducted, samples must be taken 
quickly and frozen in airtight containers to 
prevent loss due to volatilization.
IMAGING
Radiographic findings are typical of aspiration 
pneumonia and consist of fine, perihilar 
densities and extensive infiltrates in ventral 
portions of the lungs. These are worst at 3–4 
days, then gradually improve. Not all animals 
with radiographic signs of hydrocarbon 
aspiration develop respiratory signs, and 
radiographic changes usually persist past the 
• If aspiration has occurred, the principle 
lesions will be in the respiratory tract. 
Pulmonary lesions are bilateral and typically 
involve caudoventral portions of the lung. The 
earliest lesions include hyperemia, edema, and 
hemorrhage into the airways. Foreign matter 
may be grossly visible in the smaller airways. 
Later, there is bronchospasm, emphysema, and 
atelectasis. Pneumatoceles, pneumothorax, and 
subcutaneous emphysema result from airway 
collapse. There may be ulcerations in the 
mucosa of the trachea and larger airways.
• Bacterial pneumonia occasionally super -
venes and may result in abscesses.
• Systemic toxicity very occasionally results in 
hepatic, myocardial, and/or renal tubular 
necrosis if the animal survives >24 hours.
  TREATMENT
• In all cases of uncomplicated (i.e., not 
contaminated with some other, more toxic, 
substance) petroleum hydrocarbon ingestion, 
the primary goal is to minimize the risk of 
• If the amount ingested was small and the 
hydrocarbon ingested was one of the less 
volatile, more viscous products (e.g., motor 
oil, grease), cage rest and observation may be 
all that is required.
• Emetics and activated charcoal are not 
normally recommended due to potential 
vomiting and aspiration.• If the volume ingested was substantial and 
the product involved known to cause systemic 
toxicity (e.g., gasoline) or if the product 
contains other, highly toxic substances (e.g., 
pesticides), gastric decontamination may be 
indicated, despite the risk of aspiration. It is 
essential that precautions (e.g., tracheal 
intubation) be taken to prevent possible 
aspiration of stomach contents. Emetics are 
contraindicated unless an absolute last resort.
• Respiratory effects should be treated 
symptomatically. Supplemental oxygen and 
mechanical ventilation should be used as 
needed. Pneumomediastinum, pneumatoceles, 
and pneumothorax are common complications 
so positive pressure systems must be used 
with caution. High-frequency jet ventilation 
reportedly results in fewer adverse sequelae 
than conventional mechanical ventilation. 
Since the lungs are the major route of 
systemic elimination for volatile hydrocarbons, 
closed or semi-closed systems should be 
purged frequently.
• Topical exposure may be treated by gently 
bathing with warm water and a mild 
detergent shampoo. If the hair coat is heavy 
or matted, it may be necessary to clip the 
contaminated areas.
• Symptomatic treatment of petroleum burns 
may involve topical antibacterials or other 
agents.
• Very viscous hydrocarbons (e.g., tar, waxes) 
may also be removed with mild detergents. 
They are not readily absorbed, pose only a 
cosmetic and skin irritation problem, and 
removal is not critical. Lipophilic materials 
(e.g., butter, lard, mechanic’s hand cleaner) 
may also be useful, but the use of solvents is 
Cage rest is indicated, both for promotion of 
healing and to minimize the effects of 
excitement-induced catecholamines on a 
potentially sensitized myocardium.
Pet owners should be educated about proper 
storage and use of petroleum products.
• Historically, oral mineral or vegetable oil 
was recommended to increase the viscosity of 
petroleum hydrocarbons and decrease the risk 
of aspiration. Retrospective studies suggest that such treatment increases the likelihood of 
aspiration pneumonia, and the use of such 
oils is no longer recommended.
• The routine use of antibiotics is questionable. 
Hydrocarbon pneumonitis is largely 
nonbacterial in origin; however, given the 
potentially severe consequences and the 
relatively small downside to antibiotic use, it 
may be prudent to use antimicrobial 
prophylaxis if vomiting has occurred.
• Corticosteroids have been associated with 
increased numbers of positive lung cultures 
and are contraindicated.
• Bronchospasm may be treated with a 
beta-adrenergic agonist such as albuterol.
Emesis should only be used when there is a 
high degree of certainty that leaving the 
foreign material in the gut poses a greater 
hazard than aspiration.
  FOLLOW-UP
Monitor patients for 3–4 days to ensure that 
ingested hydrocarbons have cleared the 
gastrointestinal tract and no pulmonary 
sequelae will occur.
The diversity of this class of products 
precludes absolute prediction, but most 
hydrocarbon exposures respond well to 
conservative, supportive therapy.
Balme KH, Zar H, Swift DK, Mann MD. 
The efficacy of prophylactic antibiotics in 
the management of children with kerosene-
associated pneumonitis: a double-blind 
randomized controlled trial. Clin Toxicol 
(Phila). 2015 Jun 26:1–8.
Reese E, Kimbrough RD. Acute toxicity of 
gasoline and some additives. Environ 
Health Perspect 1993, 101:115–131.
Seymour FK, Henry JA. Assessment and 
management of acute poisoning by 
petroleum products. Hum Exp Toxicol 
2001, 20:551–562.
Author  Merl F . Raisbeck
Consulting Editor  Lynn R. Hovda(continued)  Petroleum Hydrocarbon Toxicosis

1076  Blackwell’s Five-Minute Veterinary Consult  
P
Pheochromocytoma
  BASICS
A tumor arising from catecholamine-
producing chromaffin cells that originate from 
neural crest cells within the adrenal medulla.
Clinical signs develop as a result of the space-  
occupying nature of the tumor and its 
metastases or from excessive secretion of 
catecholamines (e.g., causing hypertension or 
tachycardia). Signs of catecholamine release may 
be constant or intermittent. Paragangliomas are 
catecholamine-secreting tumors that arise from 
cells in the sympathetic ganglia.
• Renal.
Uncommon disease in dogs; rare in cats.
Species
None
• Median age in dogs is 11 years; range is 
1–16 years.
• Older cats.
SIGNS
• The predominant clinical signs result from 
alpha-mediated vasoconstriction and beta- 
mediated cardiac effects that cause systemic 
hypertension or tachyarrhythmias.
• Signs of hypertension may be constant or 
paroxysmal. Signs may be present for more 
than a year or develop suddenly, resulting in 
death.
• 30% of cases are asymptomatic and only 
identified at necropsy.
• Clinical signs are often episodic or acute.
• Generalized weakness and lethargy are 
common.
• Panting, dyspnea.
• Whining, pacing.
• Ascites, edema.
• Shaking/shivering.
• Epistaxis.Physical Examination Findings
• Panting, tachypnea, dyspnea.
• Pale or hyperemic mucous membranes.
• Dehydration and/or hypovolemic shock.
• Thin, muscle wasting.
• Blindness/retinal detachment.
• Peripheral edema.
• Ascites.
CAUSES
Chromaffin cell tumor.
  DIAGNOSIS
• Essential hypertension (cats).
• Renal disease with secondary hypertension.
• Other abdominal neoplasia, especially 
adrenocortical tumor (adenoma vs. adeno  - 
• Paraganglioma (rare).
• Hemoconcentration.
• Mild azotemia.
• Increased liver enzyme activities.
Arterial Blood Pressure
Systolic >160 mmHg or diastolic >100 mmHg 
represents significant hypertension. Only 
50% of animals with pheochromocytoma 
are hypertensive when blood pressure is 
measured because of the episodic nature of 
secretion of catecholamines from the tumor.
Sinus tachycardia is the most common 
arrhythmia; ventricular premature contractions 
or ventricular tachycardia less common.
IMAGING
• Mineralization of the adrenal mass (rare).
• Renal displacement.
• Abnormal renal contour.
• Ascites.
• Enlargement of the caudal venal cava.
• Pulmonary congestion or edema.Abdominal Ultrasonography
• Adrenal mass.
• T umor invasion of the caudal vena cava and 
other adjacent structures (does not differentiate 
pheochromocytoma from other adrenocortical 
tumor).
• Intra-abdominal and liver metastasis.
Other Imaging Modalities
• CT scan and MRI to evaluate invasion of 
nearby structures; superior to ultrasound for 
surgical planning.
• Scintigraphy using 123I-meta-iodobenzyl -
guanidine scan.
• The plasma half-life of catecholamines is 
short (1–3 minutes), and release from 
pheochomocytomas is episodic. However, 
catecholamine metabolites (metanephrines—
normetanephrine and metanephrine) 
constantly leak into peripheral circulation. 
Thus, measurement of metanephrines is 
preferred over measurement of catecholamines. 
Urinary normetanephrine:creatinine ratio is 
superior to the metanephrine:creatinine ratio 
for differentiating pheochromocytoma from 
hyperadrenocorticism (HAC). Additionally, 
using plasma normetanephrine concentrations 
is better than metanephrine concentrations.
• Urinary metanephrine:creatinine and 
normetanephrine:creatinine ratios:
◦ Urine must be acidified soon after 
collection, and shipped cold. Follow the 
specific instructions of the laboratory used; 
laboratory may provide a special tube with 
acid for shipping.
◦ In the United States, Marshfield Labs will 
run these ratios and provides canine 
reference ranges.
◦ No vanilla ingestion, drugs (including 
phenoxybenzamine), or radiographic contrast 
agents prior to obtaining the urine sample.
◦ Urine normetanephine:creatinine ratio 
greater than 4 times the upper limit of the 
reference range is consistent with a 
diagnosis of pheochromocytoma. Some 
cases may have ratios between (or below) 2 
and 4 times the upper limit, but so do some 
cases of HAC.
• Inhibin concentration:
◦ In one study, inhibin concentrations were 
found to be very low in neutered patients 
with and without pheochromocytoma, 
whereas the concentrations were higher in 
patients with adrenocortical tumors. Thus, 
it could be used to differentiate between 
pheochromocytoma and HAC in 
neutered dogs.
◦ No longer commercially available.
Immunohistochemical staining of tumor 
tissues with chromogranin A or synaptophysin 
allows differentiation of pheochromocytomas 
from other tumor types.

Canine and Feline, Seventh Edition  1077
P
  TREATMENT
• Surgical removal of the tumor is the 
• Medical therapy is most commonly used to 
stabilize patients prior to surgery, but may be 
elected as the sole therapy if the patient is not 
a surgical candidate due to vascular invasion 
or other factors. If the patient is not a surgical 
candidate, phenoxybenzamine, with or 
without atenolol, is used, as described under 
Drug(s) of Choice.
Survival times may be as long as 3 years 
following successful resection of tumor. 
Perioperative mortality is 20–30%, and 
decreased survival is associated with larger 
tumors (>5 cm) and invasion of nearby 
structures (such as the vena cava). In cats, 
removal of tumor is often curative; these are 
often benign, in contrast to the malignant 
tumors seen in dogs.
Preoperative Care
Medications as described under Drug(s) of 
Choice.
Complications and Patient Monitoring
Common complications—hypertension, 
severe tachycardia, other cardiac arrhythmias, 
and hypovolemia/hypotension. Postoperative 
thromboembolism has been reported.
Anesthesia
• A balanced anesthetic protocol should be 
used, with close monitoring of arterial blood 
pressure, urine output, patient volume status, 
and analgesia. Patients should have a blood 
type performed prior to surgery, and adequate 
blood products available in the event of 
perioperative hemorrhage.
• Anticipate cardiac arrhythmias (brady and 
tachyarrhythmias); ECG monitoring should 
be initiated prior to and during anesthetic 
induction.
Surgery
Unilateral adrenalectomy and often 
thrombectomy. Manipulation of the tumor 
may cause severe hypertension if patient is 
not properly premedicated.  MEDICATIONS
• Phenoxybenzamine 0.2–1.5 mg/kg PO 
q12h, should be given for 2 weeks prior to 
surgery. Start at 0.25 mg/kg twice daily and 
increase every 2–3 days to a final dose of 
1 mg/kg twice daily. Monitor blood pressure 
and decrease dose if hypotension occurs.
• Atenolol, a β1-selective antagonist 0.2–1 
mg/kg PO q12–24h to control clinically 
significant supraventricular tachycardia. Do 
not use a beta-blocker prior to using an 
alpha-blocker for at least 2 days, as hyper -
tension may become more severe.
• In the anesthetized patient or emergent 
patient with critical unresponsive 
supraventricular tachycardia—esmolol 
0.05–0.5 mg/kg IV followed by 0.01–0.2 
mg/kg/min IV may be used.
patient with critical unresponsive hypertension—  
nitroprusside 0.0005–0.005 mg/kg/min IV 
may be used.
Severe hypertension can develop if a non -
selective beta-blocker (e.g., propranolol) is 
used without prior alpha-adrenergic blockade 
(e.g., phentolamine, phenoxybenzamine).
Nonselective beta-blockade without 
alpha-blockade can lead to fatal hyper  - 
tension.
Prazosin 0.5–2.5 mg/dog PO q12h is an 
alpha-blocking drug that can be used if 
phenoxybenzamine is not available.
  FOLLOW-UP
Blood pressure, urine output, and ECG 
should be closely monitored in the immediate 
postoperative period (24–72 hours).
Perioperative—intra-abdominal hemorrhage, 
hypotension, peritonitis, sepsis.EXPECTED COURSE AND PROGNOSIS
Prognosis is guarded to fair. Dogs that survive 
the perioperative period may survive for 2–3 
years or longer. Patients that are medically 
managed can live more than a year.
Multiple endocrine neoplasia types II and III.
N/A
SEE ALSO
Hypertension, Systemic Arterial.
Barrera J, Bernard F , Ehrhart J, et al. 
Evaluation of risk factors for outcome 
associated with adrenal gland tumors with 
or without invasion of the vena cava and 
treated via adrenalectomy in dogs: 86 cases 
(1993–2009). J Am Vet Med Assoc 2013, 
242:1715–1721.
Bathez PY, Marks SL, Woo J, et al. 
Pheochromocytoma in dogs: 61 cases 
(1984–1995). J Vet Intern Med 1997, 
11(5):272–278.
Kook PH, Grest P , Quante S, et al. Urinary 
catecholamine and metadrenaline to 
creatinine ratios in dogs with a 
phaeochromocytoma. Vet Rec 2010, 
166(6):169–174.
Kyles AE, Feldman EC, De Cock HEV, et al. 
Surgical management of adrenal gland 
tumors with and without associated tumor 
thrombi in dogs: 40 cases (1994–2001). 
J Am Vet Med Assoc 2003, 223:654–662.
Reusch C. Pheochromocytoma and multiple 
endocrine neoplasia. In: Feldman EC, 
Nelson RW, Reusch CE, Scott-Moncrieff 
JCR, eds., Feline and Canine 
Endocrinology, 4th ed. Philadelphia, 
PA: Saunders, 2015, pp. 521–549.
Deborah S. Greco.(continued)  Pheochromocytoma

1078  Blackwell’s Five-Minute Veterinary Consult  
P
Phosphofructokinase Deficiency
  BASICS
OVERVIEW
• Phosphofructokinase is the most important 
rate-controlling enzyme in glycolysis, and red 
blood cells (RBCs) and intensely exercising 
skeletal muscles depend heavily on anaerobic 
glycolysis for energy.
• Affected dogs have compensated hemolytic 
anemia and mild myopathy caused by 
markedly reduced total phosphofructokinase 
activity in both tissues.
• Anemia develops because of insufficient 
generation of ATP to maintain normal RBC 
shape, ionic composition, and deformability and 
because RBCs from affected dogs are alkaline 
fragile and lyse when blood pH is slightly high.
• English springer spaniel, American cocker 
spaniel, mixed-breed, whippet, and 
wachtelhund dogs are overrepresented.
• T ransmitted as an autosomal recessive trait.
• Affected homozygous animals generally not 
recognized as abnormal before age 1.
SIGNS
• Some animals exhibit mild clinical signs 
that go unrecognized for years; others 
regularly exhibit episodes of severe illness.
• Depression or weakness concomitant with 
episodes of pigmenturia.
• Mild lethargy with slight fever during mild 
hemolytic episodes.
• Marked lethargy, weakness, pale or icteric 
mucous membranes, mild hepatosplenomegaly, 
and fever as high as 106°F (41°C) during 
severe hemolytic crises.
• Intravascular hemolysis can be caused by 
hyperventilation-induced alkalemia associated 
with exercise or excitement.
• Signs of muscle dysfunction—usually 
limited to exercise intolerance and slightly 
diminished muscle mass, but muscle cramping 
and severe progressive myopathy can occur.
• T wo affected whippets had progressive 
cardiac disease in addition to muscle 
cramping after exercise.
• Heterozygous carrier animals appear 
clinically normal.
Deficiency of the muscle-type subunit of 
phosphofructokinase—markedly reduced 
total activity in RBCs and skeletal muscle.
  DIAGNOSIS
• Other causes of hemolytic anemia—
immune-mediated hemolytic anemia, hemotropic mycoplasmosis, babesiosis, Heinz 
body anemia, microangiopathic hemolytic 
anemia, and pyruvate kinase deficiency.
• Affected dogs—negative Coombs’ test, no 
parasites or Heinz bodies in stained blood 
films, seronegative for Babesia  spp., and no 
evidence of disseminated intravascular 
coagulation or heartworm disease.
• Differentiated from pyruvate kinase 
deficiency by specific enzyme assays or DNA 
test.
• Persistent compensated hemolytic anemia.
• Mean cell volume usually 80–90 fL.
• Reticulocyte counts generally 10–30% of 
the total RBC number.
• Hematocrit values generally 30–40%; 
during hemolytic crises may decrease to 
≤15%.
• Bilirubinuria—often markedly high in male 
dogs.
• Hemoglobinuria in association with 
episodes of intravascular hemolysis.
• Serum biochemical analysis—slight 
elevations of serum potassium, magnesium, 
calcium, urea, total protein, and globulin 
concentrations and aspartate aminotransferase 
activity; slight to moderate elevation of serum 
iron and bilirubin concentrations and lactate 
dehydrogenase and alkaline phosphatase 
activities; marked hyperbilirubinemia during 
hemolytic crisis; marked azotemia if renal 
failure develops secondary to pigmentary 
nephropathy or shock.
• RBC phosphofructokinase activity—
identifiable in affected animals older than 3 
months; heterozygous carriers have 
approximately one-half normal activity.
• DNA testing to differentiate normal and 
carrier animals of any age. Wachtelhund dogs 
have a genetic mutation different from other dog 
breeds (http://research.vet.upenn.edu/penngen).
  TREATMENT
• Bone marrow transplantation is the only 
cure.
• In patients with severe intravascular 
hemolysis, IV fluid therapy minimizes the 
chance of acute renal failure.
• Blood transfusions, if anemia becomes 
life-threatening.
• Infrequently, affected dogs may die during a 
hemolytic crisis because of anemia or renal 
failure.
• Affected animals can have a normal lifespan 
if properly managed.
• Owners should avoid placing affected dogs 
in stressful situations or subjecting them to 
strenuous exercise, excitement, or high 
environmental temperatures.
http://research.vet.upenn.edu/penngen
Inal Gultekin G, Raj K, Lehman S, et al. 
Missense mutation in PFKM associated 
with muscle-type phosphofructokinase 
deficiency in the Wachtelhund dog. Mol 
Cell Probes 2012, 26:243–247.
Anim Pract 2012, 42:73–84.

Canine and Feline, Seventh Edition  1079
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Physalopterosis
  BASICS
OVERVIEW
• Physaloptera  spp. are parasitic nematodes 
that occur in dogs and cats; adults attach to 
stomach mucosa; no larval migration occurs 
outside the gastrointestinal tract.
• Infection can be asymptomatic or cause 
gastritis and vomiting.
• Typically, few worms are present; single-
worm or all-female infections are common.
• T ransmitted by ingestion of infective larvae 
in intermediate hosts (e.g., coprophagous 
grubs, beetles, cockroaches, crickets) or in 
paratenic hosts (e.g., birds, rodents, frogs, 
snakes, lizards).
Dogs and cats; any breed, age, or sex. Infected 
animals often undergo extensive workups for 
suspected inflammatory bowel disease/ulcers, 
only for the nematodes to be discovered via 
endoscopy.
SIGNS
• Vomiting, often chronic and intermittent; 
occasionally find worms in vomitus.
• Weight loss can occur, especially with 
chronic infection.
• Signs can occur without egg production 
during prepatent period, single-worm, or 
female-only infections.
• Possible melena, especially in cats.
• Outdoor exposure—access to insect 
intermediate hosts or small vertebrate 
transport hosts.
• Access to habitat occupied by wildlife 
species (raccoon, fox, coyote, bobcat, cougar, 
badger, skunk) infected with Physaloptera .
  DIAGNOSIS
• Other infectious causes of vomiting 
including parasite, viral, or bacterial 
• Spirocerca , the esophageal worm—produces 
similar but smaller eggs (11–15 × 30–37 μm).
• Ollulanus , a trichostrongylid nematode, 
can cause chronic vomiting; seen mainly in 
colony and feral cats; larvae and adults 
(<1 mm long) but no eggs present in 
vomitus or feces.
• Roundworms (ascarids) in puppies and 
kittens—worms can be present in feces and 
vomitus; larger than Physaloptera ; character -
ized by three lips and cervical alae.
• Other noninfectious causes of vomiting 
including dietary indiscretion, foreign objects 
in the stomach, noxious substances accidentally ingested, gastrointestinal 
neoplasia, metabolic diseases.
Mild anemia and eosinophilia can occur.
N/A
IMAGING
Abdominal radiography and ultrasonography, 
to eliminate other causes of vomiting.
• Endoscopy (gastroscopy) to visualize and 
remove worms, usually attached to stomach 
or duodenal mucosa; careful, thorough exam 
necessary to detect all worms; typically few 
are present and they can be hidden by mucus, 
ingesta, stomach rugae; pinpoint hemorrhages 
from prior attachment sites can be seen:
◦ Physaloptera  spp. are small (2.5–5 cm 
long), stout, white or pink, with an 
anterior cuticular collar; male and female 
P . praeputialis  have a posterior prepuce-like 
cuticular sheath.
• Direct smear, wet mount, or fecal flotation 
to detect eggs in vomitus or feces; prepatent 
period is 2–5 months; eggs are dense and can 
be difficult to detect by fecal flotation using 
low specific gravity solutions; use flotation 
solution with specific gravity >1.25:
◦ Eggs are small (42–58 × 29–42 μm), 
thick-shelled, larvated, ovoid to ellipsoidal, 
often clear and colorless.
  TREATMENT
• Outpatient treatment; anthelmintic with or 
without endoscopic removal of worms.
• Anthelmintic use is extra-label and anecdotal.
• Pyrantel pamoate (dogs/cats) 20 mg/kg PO 
every 2 weeks for at least 3 treatments; repeat 
if signs persist; treatment of choice.
• Fenbendazole (dogs) 50 mg/kg PO q24h 
for 3–5 days; repeat if signs persist.
• Ivermectin (cats) 0.2 mg/kg PO, SC, once.
• Medication to reduce gastritis—histamine 
H2-antagonists (e.g., famotidine 0.5 mg/kg 
PO q12h); sucralfate 0.25–1 g PO q8–12h.
  FOLLOW-UP
Recheck 1–2 weeks post treatment and 
re-treat with anthelmintic if eggs still present 
on fecal exam and/or if vomiting persists.PREVENTION/AVOIDANCE
• Prompt removal and disposal of feces to 
prevent infection of arthropod intermediate 
hosts.
• Prevent exposure to arthropod intermediate 
hosts.
• No products approved specifically for 
Physaloptera  spp. prevention or control; 
monthly intestinal parasite control likely 
effective to limit infections.
Clinical signs and/or shedding of eggs in feces 
should resolve within 2 weeks of treatment.
http://www.capcvet.org
Campbell KL, Graham JC. Physaloptera 
infection in dogs and cats. Compend 
Contin Educ Pract Vet 1999, 21:299–314.

1080  Blackwell’s Five-Minute Veterinary Consult  
P
Plague
  BASICS
OVERVIEW
• Yersinia pestis —Gram-negative, bipolar 
staining rod; reservoir: wild rodents (sylvatic), 
ground squirrels, prairie dogs, rabbits, 
bobcats, coyotes. • Occurs worldwide; 
movement of animals results in occurrence in 
non-endemic areas. • United States—
Western states/Hawaii. • Common May–
October. • Bacterium transmitted by infected 
fleas, also by ingestion of infected rodents; 
incubation period 2–7 days after infection. 
• Bacteria migrate from skin lymphatics to 
regional lymph nodes (LN), survive 
phagocytosis and multiply in LN; phagocytic 
cells rupture. • Fever and painful 
lymphadenopathy (bubo); intense local 
inflammation results in bubonic plague; 
intermittent bacteremia; LN rupture; may 
become septicemic with or without LN 
involvement. • Cats—severe fatal disease. 
• Dogs—naturally resistant. • Potential 
bioterrorist agent (beware of clusters of cases).
Cat and rarely dog.
SIGNS
• Dogs—exhibit mild fever/depression. 
• Cats—exhibit bubonic/pneumonic/
septicemic forms. • Bubonic (cats):
◦ Most common form. ◦ Buboes—head and 
neck; marked lymphadenopathy; if patient 
survives long enough, LN abscess, rupture, 
form fistulae to skin. ◦ Fever: 103–105°F 
(39.5–40.5°C). ◦ Lethargy, ataxia, coma. 
◦ Enlarged tonsils, oral ulcers. ◦ Vomiting, 
diarrhea, anorexia. ◦ Dehydration. ◦ Ocular 
discharge. ◦ Weight loss. • Septicemic (cats):
◦ Rare. ◦ Septicemia without lymphadenopathy 
or abscess formation. ◦ Other signs same as 
bubonic. • Pneumonic (cats): ◦ Severe disease; 
greatest risk for spread to humans (euthanasia 
strongly recommended to prevent zoonotic 
spread).
• Outdoor, hunting cats. • T ravel to endemic 
areas. • Environment—heavy flea infestation, 
large nearby rodent populations. • More 
common as homes encroach on wildlife 
habitats in plague-endemic areas.
  DIAGNOSIS
Infection (feline calicivirus, feline 
coronavirus, feline immunodeficiency virus, 
feline leukemia virus, cryptococcosis, 
histoplasmosis, toxoplasmosis, tularemia, 
leishmaniasis), neoplasia, drug eruption/skin 
hypersensitivity, epidermolysis bullosa, pemphigus, systemic lupus erythematosus, 
oropharyngeal foreign body, trauma, 
gingivitis, stomatitis, osteomyelitis, 
sequestrum.
• Leukocytosis: left shift/marked toxic 
change. • Thrombocytopenia. • High liver 
enzyme activity and hyperbilirubinemia.
• Serology—Communicable Disease Center/
state health department. • Fluorescent 
antibody test—presumptive identification. 
• Molecular testing—PCR of blood/tissues. 
• Coagulation profile—prolonged with 
• Culture is definitive; sample abscess, LN, 
peripheral blood before treatment is given or 
culture from post-mortem tissue (LN, 
abscess, liver, spleen). • Impression smears of 
tissue—large numbers of Gram-negative 
coccobacilli with bipolar staining. • Thoracic 
radiographs may show nodular lesions with 
pneumonic plague.
• Acutely ill cats—few lesions; enlarged head 
and neck LN; enlarged liver and spleen. 
• LN—destruction of normal architecture, 
hemorrhagic necrosis, extracellular bacteria.
  TREATMENT
• Inpatient. • High mortality if not treated 
early. • T reat sepsis aggressively (see Sepsis 
and Bacteremia). • T reat for fleas.
• T reat all suspect cases empirically pending 
confirmation. • Systemic antimicrobials: 
◦ Tetracycline 20 mg/kg PO q8h for 21–42 
days. ◦ Doxycycline 5–10 mg/kg PO q12h; 
likely effective (not definitively established). 
◦ Chloramphenicol 30–50 mg/kg PO q8h. 
◦ Aminoglycosides, trimethoprim-
sulfamethoxazole—also likely effective. 
• Coordinate with public health officials; 
bioengineered strains may be drug resistant.
  FOLLOW-UP
Consumptive coagulopathy common later in 
• Avoid travel to endemic areas. • Endemic areas—keep pet on leash; use flea control on 
pet and home. • Limit cat hunting behavior/
rodent exposure. • Eliminate rodents/habitats 
near houses/outbuildings; store food in 
rodent-proof containers.
• Duration of illness variable. • Prognosis—
poor if not treated early. • Pneumonic plague 
has greatest risk of death.
High
CDC Recommendations
• Notify public health officials. • Avoid 
contact with infectious materials from 
patient, fleas. • Disinfect/autoclave/incinerate 
any material used in examination of patients. 
• Isolate patients and wear mask/gloves when 
handling. • Assess pulmonary involvement. 
• Use respirator/protective eye equipment 
during necropsies. • Monitor staff for 2 
weeks post exposure; discuss postexposure 
prophylaxis/fever watch with health care 
provider.
• http://www.cfsph.iastate.edu/DiseaseInfo/
disease.php?name=plague&lang=en • https://
www.cdc.gov/plague/prevention/index.html
Kassem AM, Tengelsen L, Atkins B, et al. 
Notes from the field: plague in domestic 
cats—Idaho, 2016. Morb Mortal Wkly Rep 
2016, 65:1378–1379.
Pennisi MG, Egberink H, et al. Yersina pestis  
infection in cats: ABCD guidelines on 
Surg 2013, 15:582–584.

Canine and Feline, Seventh Edition  1081
P
Plasmacytoma, Mucocutaneous
  BASICS
OVERVIEW
• T umor of plasma cell origin.
• Typically benign and local therapy can be 
curative.
• Rarely (<1%) part of multiple myeloma 
process.
• Gastrointestinal extramedullary plasma­
cytoma (GI EMP) may be more aggressive.
• Dog, rarely cat.
• Cocker spaniel, West Highland white 
terrier, boxer, German shepherd dog, 
Airedale.
• Median age 9–10 years.
SIGNS
• 86% are cutaneous, 9% affect mucous 
membranes, 4% colorectal, 1% noncutaneous/  
non­oral.
• Solitary, smooth, raised pink nodules, 
typically 1–2 cm in diameter.
• Bleeding, hematochezia, tenesmus, rectal 
prolapse if colorectal form.
• Vague, nonspecific signs if GI EMP .
Unknown
  DIAGNOSIS
• Other round cell tumor types including 
lymphoma, mast cell tumor, histiocytoma, 
transmissible venereal tumor.
• Poorly differentiated carcinoma.
Usually normal for EMP
Bone marrow aspirate cytology and serum 
electrophoresis may be indicated for GI EMP .
IMAGING
• Colonoscopy recommended for colorectal 
EMP .
• Thoracic radiographs and abdominal 
ultrasound may be indicated for GI EMP .
aspirate reveals moderate to marked cellularity 
with round to polyhedral individual tumor 
cells with discrete margins, abundant royal 
blue cytoplasm, paranuclear clear zone, 
eccentric round nucleus, and clumped 
chromatin. Multinuclearity is common.
• Histologic evaluation—classified into 
mature, hyaline, cleaved, asynchronous, 
monomorphous blastic, and polymorphous 
blastic cell types. However, no prognostic significance has been associated with this 
classification.
distinguish from other neoplasms.
  TREATMENT
• Conservative surgery.
• Radiation therapy if nonresectable.
Melphalan and prednisone or single ­agent 
lomustine may be indicated in GI EMP or 
multiple tumors.
N/A
  FOLLOW-UP
Reevaluation every 3 months to monitor for 
local tumor control and metastases.
• Excellent in most patients.
• Long ­term survival expected for GI EMP 
treated with surgery ± chemotherapy.
• Reported 15 ­month median survival time 
for colorectal form with surgery alone.
• 5% local recurrence rate with conservative 
surgery for the majority of EMP .
• Metastasis reported in 2% of patients with 
EMP .
• 2% of patients will develop de novo  EMP .
• Multiple myeloma.
• Lymphoma—dogs.
• Cats—may note systemic amyloidosis.
SEE ALSO
• EMP = extramedullary plasmacytoma.
Cangul IT, Wijnen M, Van Garderen E, et al. 
Clinico ­pathological aspects of canine 
cutaneous and mucocutaneous plasmacytomas. 
J Vet Med A Physiol Pathol Clin Med 2002, 
49(6):307–312.Morrison WB. Plasma cell neoplasms. In: 
Morrison WB, ed., Cancer in Dogs and 
Cats: Medical and Surgical Management. 
Jackson, WY: Teton NewMedia, 2002, pp. 
671–677.
Vail D. Myeloma ­Related Disorders. In: 
665–678.

1082  Blackwell’s Five-Minute Veterinary Consult  
P
Pleural Effusion
  BASICS
Abnormal accumulation of fluid within the 
pleural cavity.
• More than normal production or less than 
normal resorption of fluid. • Alterations in 
hydrostatic and oncotic pressures or vascular 
permeability and lymphatic function may 
contribute to fluid accumulation.
Species
• Young animals—more commonly infection.
• Old animals—more commonly cardiac or 
neoplastic.
SIGNS
Depend on the fluid volume, rapidity of fluid 
accumulation, and the underlying cause.
• Dyspnea. • Tachypnea. • Orthopnea. 
• Open-mouth breathing. • Cyanosis. 
• Exercise intolerance. • Lethargy. 
• Inappetence. • Cough.
• Dyspnea—respirations often shallow and rapid. 
• Muffled or inaudible heart and lung sounds 
ventrally. • Preservation of breath sounds 
dorsally. • Dullness ventrally on thoracic 
percussion.
CAUSES
High Hydrostatic Pressure
• Congestive heart failure (CHF). 
• Overhydration. • Intrathoracic neoplasia.
Low Oncotic Pressure
Hypoalbuminemia—occurs in protein-losing 
enteropathy, protein-losing nephropathy, and 
Vascular or Lymphatic Abnormality
• Infectious—bacterial, viral, or fungal. 
• Neoplasia (e.g., mediastinal lymphoma, 
thymoma, mesothelioma, primary lung 
tumor, and metastatic disease). • Chylothorax 
(e.g., from lymphangiectasia, CHF , cranial 
vena caval obstruction [sometimes associated 
with transvenous pacemaker implantation], 
neoplasia, fungal infections, heartworms, 
diaphragmatic hernia, lung lobe torsion, trauma). • Diaphragmatic hernia. 
• Hemothorax (e.g., from trauma, neoplasia, 
coagulopathy, Angiostrongylus vasorum ). 
• Lung lobe torsion. • Pulmonary thrombo -
embolism. • Pancreatitis.
  DIAGNOSIS
• Historical or physical evidence of external 
trauma—consider hemothorax or 
diaphragmatic hernia. • Fever suggests an 
inflammatory, infectious, or neoplastic cause. 
• Murmurs, gallops, or arrhythmias 
combined with jugular venous distension or 
pulsation suggest an underlying cardiac cause. 
• Concurrent ascites suggests feline infectious 
peritonitis (FIP), CHF (mainly dogs), severe 
hypoalbuminemia, diaphragmatic hernia, 
disseminated neoplasia, or pancreatitis. • In 
cats, decreased compressibility of the cranial 
thorax suggests a cranial mediastinal mass. 
• Concurrent ocular changes (e.g., chorio -
retinitis and uveitis) suggest FIP or fungal 
disease. • Hypothermia often associated with 
cardiac cause.
• Hemogram results may be abnormal in 
patients with pyothorax, FIP , neoplasia, or 
lung lobe torsion. • Severe hypoalbuminemia 
(generally <1 g/dL to cause effusion) suggests 
protein-losing enteropathy, protein-losing 
nephropathy, or liver disease. 
• Hyperglobulinemia (polyclonal) 
suggests FIP .
• Fluid analysis should include physical 
characteristics (i.e., color, clarity, odor, clots), 
pH, glucose, total protein, total nucleated cell 
count, and cytologic examination; Table 1 
provides characteristics of various pleural 
fluid types and their disease associations. • In 
cats the lactate dehydrogenase concentration 
in transudates is <200 IU/L and in exudates it 
is >200 IU/L. • Pleural fluid pH <6.9 
suggests pyothorax in cats. • Glucose 
concentration in pleural fluid usually parallels 
levels in serum. In cats, pyothorax and 
malignancy lower pleural fluid glucose 
concentration relative to serum glucose 
concentration; thus, pleural fluid with a 
normal pH and low glucose concentration 
suggests malignancy in cats. • Serologic tests 
for feline leukemia virus (if patient has 
mediastinal lymphoma), feline immuno -
deficiency virus (if patient has pyothorax), 
and coronavirus (if FIP is suspected) are 
available. • Cardiac disease suspected—
consider a heartworm test in dogs and cats; 
NT-proBNP and thyroid evaluation in cats. 
• Infection suspected—obtain aerobic and 
anaerobic bacterial culture and sensitivity tests and consider special stains (e.g., Gram 
and acid-fast stains) of the fluid. • FIP 
suspected—consider protein electrophoresis of the 
fluid; gamma-globulin level >32% of total protein 
strongly suggests a diagnosis of FIP . • Chyle 
suspected—do an ether clearance test or 
Sudan stain of the pleural fluid, and 
triglyceride and cholesterol evaluations of the 
fluid and serum.
IMAGING
• Used to confirm pleural effusion; should 
not be performed until after thoracocentesis 
in dyspneic patients with evidence of pleural 
effusion on physical examination. • Evidence 
of pleural effusion includes separation of lung 
borders away from the thoracic wall and 
sternum by fluid density in the pleural space, 
fluid-filled interlobar fissure lines, loss or 
blurring of the cardiac and diaphragmatic 
borders, blunting of the lung margins at the 
costophrenic angles (ventrodorsal view), and 
widening of the mediastinum (ventrodorsal 
view). • Rounding of the caudal lung lobe 
borders (lateral view)—most common in 
patients with fibrosing pleuritis caused by 
chylothorax, pyothorax, or FIP . • Unilateral 
effusion—most common in patients with 
chylothorax and pyothorax; hemothorax, 
pulmonary neoplasia, diaphragmatic hernia, 
and lung lobe torsion. • Evaluate post-
thoracocentesis radiographs carefully for 
cardiomegaly, intrapulmonary lesions, 
mediastinal masses, diaphragmatic hernia, 
lung lobe torsion, and evidence of trauma 
(e.g., rib fractures). • Can diagnose a 
diaphragmatic hernia with positive-contrast 
peritoneography. • Can evaluate the thoracic 
duct by positive-contrast lymphangiography. 
• CT imaging may help differentiate 
malignant from inflammatory effusions.
• Ultrasonographic evaluation of the thorax is 
recommended whenever cardiac disease, 
diaphragmatic hernia, or cranial mediastinal 
mass is suspected. • Echocardiography is 
easiest to perform before thoracocentesis, 
provided the patient is stable.
• Thoracocentesis—allows characterization 
of the fluid type and determination of 
potential underlying cause. • Exploratory 
thoracotomy or thoracoscopy—to obtain 
biopsy specimens of lung, lymph nodes, or 
pleura, if indicated.
  TREATMENT
• First, thoracocentesis to relieve respiratory 
distress; if the patient is stable after 
thoracocentesis, outpatient treatment may be 
possible for some diseases. Most patients are

Canine and Feline, Seventh Edition  1083
P
hospitalized because they require intensive 
management such as indwelling chest tubes 
(e.g., patients with pyothorax) or thoracic 
surgery. • Preventing fluid reaccumulation 
requires treatment based on a definitive 
diagnosis. • Surgery is indicated for 
management of some neoplasias, diaphragmatic 
hernia repair, lymphangiectasia (i.e., thoracic 
duct ligation), foreign body removal, and 
lung lobe torsion (i.e., lung lobectomy). 
• Pleuroperitoneal shunts may relieve clinical 
signs in animals with intractable pleural effusion. 
• Vascular access ports attached to 
intrathoracic Jackson–Pratt drains can be 
tried for chronic effusions that are not 
responsive to the therapy of the underlying 
disorder.
• T reatment varies with specific disease. 
• Diuretics generally reserved for patients 
with diseases causing fluid retention and 
volume overload (e.g., CHF).
• Avoid drugs that depress respiration or 
decrease blood pressure. • Inappropriate use 
of diuretics predisposes the patient to dehydration and electrolyte disturbances 
without eliminating the effusion.
  FOLLOW-UP
Radiographic evaluation is key to assessment 
of treatment in most patients.
• Death due to respiratory compromise. 
• Reexpansion pulmonary edema may develop 
after pleural effusion is manually removed.
Varies with underlying cause, but usually 
guarded to poor. In a study of 81 cases of 
pleural effusion in dogs, 25% recovered 
completely and 33% died during or were 
euthanized immediately after completing 
diagnostic evaluation.
SYNONYMS
• Hydrothorax = transudates and modified 
transudates. • Pyothorax = empyema, septic 
pleuritis.ABBREVIATIONS
• CHF = congestive heart failure. • FIP = 
feline infectious peritonitis. • LSA = 
lymphoma. • PMN = polymorphonuclear 
cell. • RBC = red blood cell.
Epstein SE. Exudative pleural diseases in 
Anim Pract 2014, 44(1):161–180.
König A, Hartmann K, Mueller RS, et al. 
Retrospective analysis of pleural effusion in cats. 
J Feline Med Surg 2019, 21(12):1102–1110.
Mellanby RJ, Villiers E, Herrtage ME. 
Canine pleural effusions: a retrospective 
study of 81 cases. J Small Anim Pract 2002, 
43(10):447–451.
Ruiz MD, Vessieres F , Ragetly GR, Hernandez 
JL. Characterization of and factors associated 
with causes of pleural effusion in cats. J Am 
Vet Med Assoc 2018, 253(2):181–187.
Smeak DD, Birchard SJ, McLoughlin MA, 
et al. T reatment of chronic pleural effusion 
with pleuroperitoneal shunts in dogs: 
14 cases (1985–1999). J Am Vet Med Assoc 
2001, 219(11):1590–1597.
available online(continued)  Pleural Effusion
Table 1
Characterization of pleural fluid.
Transudate Modified Transudate Nonseptic Exudate Septic Exudate Chyle Hemorrhage
Color Colorless to pale 
yellowYellow or pink Yellow or pink Yellow to red-brown Milky white Red
Turbidity Clear Clear to cloudy Clear to cloudy; 
fibrinCloudy to opaque; 
fibrinOpaque Opaque
Protein (g/dL) <1.5 2.5–5.0 3.0–8.0 3.0–7.0 2.5–6.0 3.0
Nucleated 
cells/μL<1,000 1,000–7,000 (LSA up 
to 100,000)5,000–20,000 (LSA 
up to 100,000)5,000–300,000 1,000–20,000 Similar to peripheral 
blood
Cytology Mostly 
mesothelial 
cells and 
macrophagesMostly macrophages 
and mesothelial 
cells; few 
nondegenerate 
PMNs; neoplastic 
cells in some casesMostly 
PMNs and 
macrophages; 
neoplastic cells 
in some casesMostly degenerate 
PMNs; also 
bacteriaSmall lymphocytes, 
PMNs, and 
macrophagesMostly RBCs;with 
erythrophagocytosis
Disease 
associationsHypoalbuminemia 
(protein-losing 
nephropathy, 
protein-losing 
enteropathy, or 
liver disease); 
early CHFCHF; neoplasia; 
diaphragmatic 
hernia; pancreatitisFIP; neoplasia; 
hernia; lung 
lobe torsionPyothorax Lymphangiectasia, CHF , 
cranial vena cava 
obstruction, neoplasia, 
fungal, dirofilariasias, 
diaphragmatic hernia, 
lung lobe torsion, 
traumaTrauma, coagulopathy, 
neoplasia, lung lobe 
torsion
Source: Modified from Sherding RG. Diseases of the pleural cavity. In: Sherding RG, ed., The Cat: Diseases and Clinical Management, 2nd ed. New York: Churchill 
Livingstone, 1994, p. 1061.

1084  Blackwell’s Five-Minute Veterinary Consult  
P
Pneumocystosis
  BASICS
OVERVIEW
• Pneumocystis  spp.—saprophyte/commensal 
of low virulence; infect virtually all mammals 
worldwide. ◦ Pneumocystis carinii  f. sp. canis: 
organism infecting dogs (hereafter “ Pneumocystis 
canis”). • Primary habitat is lung. • Atypical 
fungal organism, based on nucleic acid 
sequencing; exhibits behavior more typical of 
protozoa. • Subclinical infections in cats and 
dogs; clinical infections in dogs linked with 
immunodeficiency; clinical infection not 
reported in cats even with 
• Young dogs (<1 year of age). • Miniature 
dachshunds and cavalier King Charles 
spaniels (CKCS, worldwide), Pomeranians (in 
Japan) predisposed (congenital 
immunodeficiencies).
SIGNS
• Progressive respiratory difficulty (weeks 
to months). • Dyspnea and tachypnea, 
cyanosis. • Exercise intolerance. • Cough. 
• Fever uncommon. • Inappetence, weight 
loss, and thin body condition. • Some 
dogs have concurrent generalized 
demodicosis.
• Spread by airborne droplets. Neonates may 
be infected at birth. • Congenital or acquired 
immunodeficiency predisposes to develop­
ment of clinical disease: ◦ Severe immuno­
suppression—deficiency of IgA, IgG, IgM in 
dachshunds; immunoglobulin deficiency and 
decreased lymphocyte function in CKCS.
  DIAGNOSIS
• Inflammatory (chronic pulmonary fibrosis, 
eosinophilic bronchopneumopathy, 
inhalational irritants). • Infection (viral, 
bacterial, fungal, protozoal or parasitic 
pneumonia). • Pulmonary edema (cardiogenic 
or noncardiogenic). • Thromboembolism. 
• Usually nonspecific. • Leukocytosis with 
neutrophilia and a left shift. • Eosinophilia 
and monocytosis. • Erythrocytosis—secondary 
to chronic hypoxia. • Thrombocytopenia 
(CKCS) or thrombocytosis (dachshunds). 
• Variable hypoglobulinemia.
• Arterial blood gas—hypoxemia; hypocapnia. 
• Immunoglobulin fraction quantification—
hypogammaglobulinemia. • Indirect or direct fluorescent antibody test—detect organism in 
sputum, washes, and pulmonary tissues. 
• PCR of bronchoalveolar fluid and tissues.
IMAGING
• Diffuse miliary—interstitial to alveolar pattern 
with peribronchial opacification. • Middle lung 
lobes may be more severely affected. • Rarely 
cavitary lesions and pneumothorax.
CT
Diffuse to multifocal “ground ­glass” 
appearance with variable bronchial bands; 
signs consistent with pulmonary hypertension.
• T ranstracheal aspiration, bronchoalveolar 
lavage, transbronchoscopic and endobronchial 
brushing: ◦ Direct visualization of P . canis . 
• Biopsy for histopathology (cytology not as 
sensitive or specific): ◦ Invasive, potential 
complications of hemorrhage, pneumothorax. 
• PCR assays for P . canis— interpreted in light 
of consistent clinical signs and other 
diagnostic findings because of subclinical 
infection in dogs; assays designed to detect 
P . jirovecii  may not detect P . canis .
• Lungs—firm, consolidated, pale brown or 
gray; fluid not expressed from cut surfaces; do 
not collapse when chest cavity opened; alveoli 
may be filled with amorphous, foamy, 
eosinophilic material with honeycomb 
appearance; trophozoites and cyst stages may 
be identified. • Pulmonary and mediastinal 
lymphadenopathy. • Right ­sided cardio­
megaly. • H&E only weakly stains internal 
structures of organism; methenamine silver, 
toluidine blue, Gram and periodic acid–Schiff 
will stain cyst walls.
  TREATMENT
• Inpatient—supportive care for pneumonia: 
oxygen, nebulization, bronchodilators, IV 
fluids as required. • Discontinue immuno­
suppressant agents. • Cage rest.
• T rimethoprim ­sulfonamide 15–20 mg/kg 
PO q8h or 30 mg/kg PO q12h for 3 weeks—
preferred therapy (IV may be more effective 
than PO in humans). • Alternative 
treatments—pentamidine isethionate 4 mg/kg 
IM q24h for 3 weeks; atovaquone 15 mg/kg 
PO q24h for 3 weeks (not as effective but less 
toxic); combination of clindamycin and 
primaquine or dapsone and trimethoprim. 
• Potential new drug options—caspofungin 
(no veterinary cases reported) and trimetrexate. • Short ­term treatment with anti ­inflammatory 
doses of glucocorticoids may be beneficial.
• Pentamidine isethionate—renal and hepatic 
dysfunction (check renal parameters daily 
during therapy), hypoglycemia, hypotension, 
hypocalcemia, urticaria, and hematologic 
disorders. • T rimethoprim ­sulfonamides—
keratoconjunctivitis sicca, thrombocytopenia.
  FOLLOW-UP
• Monitor clinical signs, radiographs; may 
need months ­long treatment. • For side 
effects of medications.
Ubiquitous in environment; humans and 
animals are exposed to same sources.
• CKCS = cavalier King Charles spaniel.
Danesi P , Ravagnan S, Johnson L, et al. 
Molecular diagnosis of Pneumocystis  
pneumonia in dogs. Med Mycol 2017, 
55(8):828–842.
Weissenbacher ­Lang C, Fuchs ­Baumgartinger 
A, Guija ­De­Arespacochaga, et al. 
Pneumocystosis in dogs: meta ­analysis of 43 
published cases including clinical signs, 
diagnostic procedures, and treatment. J Vet 
Diagn Invest 2018, 30(1):26–35.
Hannah N. Pipe ­Martin and Steven C. Barr.

Canine and Feline, Seventh Edition  1085
P
Pneumonia, Aspiration
  BASICS
OVERVIEW
• Inflammation of the lungs caused by 
inhalation of oral ingesta, regurgitated 
material, and vomitus with subsequent 
pulmonary dysfunction; develops when 
laryngeal reflexes function improperly or are 
overwhelmed. • Pulmonary dysfunction—
caused by (1) direct obstruction of small 
airways and indirect obstruction from 
bronchospasm and production of mucus and 
exudate; (2) aspiration of gastric acid—
damages respiratory epithelium; can cause 
bronchospasm and acute lung injury/acute 
respiratory distress syndrome (ALI/ARDS); 
(3) bacterial pneumonia—bacteria in 
aspirated material can initiate an immediate 
infection; or later infections occur secondary 
to lung damage.
Dogs; less commonly cats.
SIGNS
• Peracute, acute, or chronic. • Cough, 
tachypnea, nasal discharge, or exercise 
intolerance. • Respiratory distress or cyanosis 
when severe. • Depending on underlying 
cause—regurgitation; vomiting; dysphagia; 
altered consciousness; stertor or stridor.
• Pharyngeal abnormalities—local paralysis; 
generalized neuromuscular disease; 
cricopharyngeal motor dysfunction; anatomic 
malformations. • Esophageal abnormalities—
megaesophagus; reflux esophagitis; esophageal 
dysmotility; esophageal obstruction; broncho­
esophageal fistula. • Laryngeal paralysis, 
webbing, or obstruction; post ­laryngeal 
surgery. •Altered consciousness—sedation, 
anesthesia; post ­ictus; forebrain disease; 
metabolic disturbance. • Iatrogenic—force 
feeding; tube feeding, mineral oil 
  DIAGNOSIS
• Bacterial pneumonia. • Lung abscess.
Neutrophilic leukocytosis, left shift, although 
white blood cells may be normal.
• Arterial blood gas analysis—hypoxemia; 
Paco2 generally low. • Consider tests for 
predisposing problems—acetylcholine 
receptor antibodies, resting cortisol or 
adrenocorticotropic hormone stimulation, 
creatine kinase.IMAGING
• Thoracic radiography—bronchoalveolar 
pattern usually most severe in the gravity ­
dependent lobes (right cranial and middle, 
left cranial); can take up to 24 hours for 
pattern to develop after aspiration; scrutinize 
for evidence of esophageal or mediastinal 
disease. • Videofluoroscopic swallowing 
study—provides evidence of swallowing or 
esophageal dysfunction that can predispose to 
aspiration. Caution: could result in aspiration 
of contrast medium.
• T racheal wash—for bacterial culture and 
sensitivity testing before administering 
antibiotics; infection often caused by multiple 
organisms with unpredictable susceptibility. 
• Bronchoscopy—rarely indicated. 
• Laryngeal function examination—always 
perform if patient anesthetized for other 
purposes; otherwise, after resolution of 
pneumonia if supportive clinical signs.
  TREATMENT
• Oxygen and cage rest—respiratory distress. 
• Ventilatory support—if not oxygen 
responsive. • IV fluids—avoid overhydration, 
which can exacerbate secondary edema. 
• Oral intake—withhold until primary 
problem identified and managed. • Do not 
allow patient to remain laterally recumbent 
on one side for more than 2 hours. • Mild 
exercise and saline nebulization with coupage 
can facilitate airway clearance. • Airway 
suction—only if performed immediately 
following aspiration (such as during recovery 
from anesthesia). • Airway 
lavage—contraindicated.
• Antibiotic therapy—if signs of sepsis or 
severe compromise, ampicillin with sulbactam 
(20 mg/kg IV q8h) plus a fluoroquinolone 
IV. Adjust antibiotic selection based on results 
of airway cytology, culture and sensitivity, and 
clinical response; continue for 10 days after 
resolution of clinical and radiographic signs; 
if no signs of sepsis, ampicillin with 
sulbactam pending results of culture. 
• Beta­agonist bronchodilators—sometimes 
cause dramatic improvement but have the 
potential to worsen ventilation:perfusion 
mismatch; most often helpful in acute 
aspiration or with auscultable wheezes. 
• Short ­acting corticosteroids—consider for 
up to 48 hours to combat inflammation 
associated with life ­threatening aspiration.CONTRAINDICATIONS/POSSIBLE 
• Diuretics—generally contraindicated; drying of 
airways reduces mucociliary clearance. 
• Corticosteroids—contraindicated beyond initial 
stabilization; predispose patient to infection. 
• Fluoroquinolones and chloramphenicol—
can prolong clearance of theophylline ­derivative 
bronchodilators; decrease theophylline dosage by 
30–50% or prolong dosing interval.
  FOLLOW-UP
• Radiographs—evaluate every 2–7 days 
initially to determine appropriateness of 
treatment; then every 1–2 weeks. • If signs do 
not resolve or suddenly worsen—possible 
recurrence of aspiration or a secondary 
infection; repeat diagnostic evaluation, 
including tracheal wash or bronchoscopy.
• Predisposed patients undergoing 
anesthesia—cisapride (slow infusion, 1 mL/kg 
over 30 minutes) 1–2 hours pre ­induction 
may decrease esophageal reflux. • Suction 
esophagus prior to extubation. • Antacids 
could decrease acid ­related lung injury in 
predisposed patients; may also increase risk of 
• Secondary infection common. • ALI/ARDS. 
• Abscessation or granuloma formation rare.
• Prognosis—depends on severity of signs 
and ability to correct underlying disease. 
• Severe aspiration—can be fatal. 
• Recurrence—likely if underlying cause not 
SEE ALSO
• Acute Respiratory Distress Syndrome. 
• Megaesophagus. • Pneumonia, Bacterial.
• ALI/ARDS = acute lung injury/acute 
respiratory distress syndrome.
Antimicrobial use guidelines for the 
treatment of respiratory tract disease in dogs 
and cats: Antimicrobial Guidelines Working 
Group of the International Society for 
Companion Animal Infectious Diseases. 
J Vet Intern Med 2017, 31:279–294.
Author  Eleanor C. Hawkins

1086  Blackwell’s Five-Minute Veterinary Consult  
P
Pneumonia, Bacterial
  BASICS
Acquired inflammatory response to bacteria 
in lung parenchyma characterized by 
exudation of cells and fluid into conducting 
airways and alveolar spaces.
• Bacteria—enter the lower respiratory tract 
primarily by inhalation or aspiration; less 
commonly by the hematogenous route. 
Infection incites an inflammatory reaction. 
• T racheobronchial tree and carina—
normally not sterile. • Oropharyngeal 
bacteria—frequently aspirated; may be 
present for an unknown time period in the 
normal tracheobronchial tree and lung; can 
cause or complicate respiratory infection; 
presence complicates interpretation of airway 
and lung cultures. • Respiratory infection—
development depends on the complex 
interplay of many factors: inoculation site, 
number of organisms and their virulence, and 
age and resistance of the host. • Bacteria 
produce extracellular proteins called invasins 
that impair host defenses and assist in the 
spread of bacteria. • Viral infections—alter 
bacterial colonization patterns; increase 
bacterial adherence to respiratory epithelium; 
reduce mucociliary clearance and phagocytosis; 
allow resident bacteria to invade the lower 
respiratory tract. • Foreign body—inoculates 
bacteria into a focal lung region and leads to 
obstructive pneumonia. • Exudative phase—
inflammatory hyperemia; extravasation of 
high-protein fluid into interstitial and alveolar 
spaces. • Leukocytic migration phase—
leukocytes infiltrate the airways and alveoli; 
consolidation, ischemia, tissue necrosis, and 
atelectasis owing to bronchial occlusion, 
obstructive bronchiolitis, and impaired 
collateral ventilation.
Respiratory—primary or secondary infection.
GENETICS
Heritable rhinitis/bronchopneumonia syndrome 
of Irish wolfhounds, unknown pathogenesis.
Common in both young and old dogs, less 
Species
Dogs—sporting breeds, hounds, working 
breeds, and mixed breeds >12 kg.
Dogs—range, 1 month–15 years.Predominant Sex
Dogs—60% males.
SIGNS
• Cough. • Labored breathing. • Recent 
vomiting/regurgitation (aspiration). 
• Anorexia. • Lethargy. • Nasal discharge.
• Cough. • Fever. • Difficult or rapid 
breathing. • Abnormal breath sounds on 
auscultation—increased intensity, crackles, 
and wheezes. • Nasal discharge. • Lethargy. 
CAUSES
Dogs
• Most common primary pathogens—
Bordetella bronchiseptica  and Mycoplasma  spp. 
• Most common Gram-positive bacteria—
Staphylococcus , Streptococcus , and Enterococcus  
spp. • Most common Gram-negative bacteria —
Escherichia coli , Klebsiella  spp., Pseudomonas  
spp., Pasteurella  spp. • Anaerobic bacteria—
found in pulmonary abscesses and various types 
of pneumonia (particularly with aspiration or 
foreign bodies); reported in ∼20% of cases.
Cats
• Bacterial pathogens—poorly documented; B. 
bronchiseptica , Pasteurella  spp., and Moraxella  
spp. most frequently reported. Mycoplasma  
spp. may be a primary pathogen in the lower 
respiratory tract. • Carrier state—may exist; 
periods of shedding B. bronchiseptica  after 
stress; infected queens may not shed organism 
prepartum but begin shedding post partum, 
serving as a source of infection for kittens.
• Prior viral infection. • Regurgitation, 
dysphagia, or vomiting. • Functional or 
anatomic defects—laryngeal paralysis, 
brachycephalic breed, megaesophagus, cleft 
palate, primary ciliary dyskinesia. • Reduced 
level of consciousness—stupor, coma, and 
anesthesia. • Bronchial foreign body. 
• Bronchiectasis. • Immunosuppressive 
therapy—chemotherapy, glucocorticoids. 
• Severe metabolic disorders—uremia, 
diabetes mellitus, hyperadrenocorticism. 
• Sepsis. • Age—very young more susceptible 
to fatal infections. • Immunization status. 
• Environment—housing, sanitation, 
ventilation. • Phagocyte dysfunction—feline 
leukemia virus and diabetes mellitus. 
• Complement deficiency—rare. • Selective 
IgA deficiency—rare. • Combined T-cell and 
B-cell dysfunction—rare.
  DIAGNOSIS
• Viral pneumonia (canine distemper virus, 
adenovirus, influenza virus, herpesvirus). • Protozoal pneumonia ( Toxoplasma ). 
• Parasitic pneumonia (capillariasis, 
filaroidiasis, lungworm). • Fungal pneumonia 
(Histoplasma , Blastomyces, Coccidioides , 
Cryptococcus ). • Eosinophilic pneumonia. 
• Feline bronchial disease (asthma). 
• Pulmonary abscess. • Pleural infection 
(pyothorax). • Bronchial foreign body.
Inflammatory leukogram—neutrophilic 
leukocytosis with or without a left shift; 
absence does not rule out the diagnosis.
• Arterial blood gas analysis—values correlate 
well with the degree of physiologic 
disruption; sensitive monitor of progress 
during treatment; Pao2 <80 mmHg on room 
air = mild or moderate hypoxemia; Pao2 
<60mmHg on room air = severe hypoxemia. 
• Consider viral serology. • Molecular 
diagnostics also available for viral and 
bacterial presence.
IMAGING
• Variable—diffuse, bronchointerstitial 
pattern, partial or complete alveolar 
infiltrates, consolidation. • Most common—  
alveolar pattern characterized by increased 
pulmonary densities (margins indistinct; air 
bronchograms or lobar consolidation). 
• More variable lung patterns in cats such as 
multifocal, patchy interstitial and alveolar 
changes and/or a diffuse nodular pattern.
• Microbiologic (aerobic, anaerobic, and 
Mycoplasma  culture) and cytology for 
definitive diagnosis. • Samples—
transtracheal or endotracheal washing, 
bronchoscopy, bronchoalveolar lavage (with 
or without bronchoscope), or fine-needle 
lung aspiration. • Degenerate neutrophils 
with septic inflammation (intracellular 
bacteria) predominating. • Recent 
antibiotic administration—nonseptic 
inflammation likely. • Bacteria—not always 
obvious microscopically; always culture 
specimens even if no bacteria are seen on 
cytology.
• Irregular consolidation in cranioventral 
regions. • Consolidated lung—varies 
from dark red to gray-pink to more gray, 
depending on age of patient and nature of 
the process. • Palpable firmness of the tissue. 
• Nidus of inflammation—bronchiolar-
alveolar junction. • Early—bronchioles and 
adjacent alveoli filled with neutrophils 
and an admixture of cell debris, fibrin, and 
macrophages; necrotic to hyperplastic 
epithelium. • Later—neutrophilic, fibrinous, 
hemorrhagic, or necrotizing inflammation 
depending on virulence of bacteria and host 
response.

Canine and Feline, Seventh Edition  1087
P
  TREATMENT
Inpatient—recommended with multisystemic 
signs (e.g., anorexia, fever) or in patients with 
respiratory compromise in the absence of 
multisystemic signs.
• Maintain normal systemic hydration—
important to aid mucociliary clearance and 
secretion mobilization; use a balanced electrolyte 
solution. • Saline nebulization—results in more 
rapid resolution if used with physical therapy and 
systemic antimicrobials. • Physical therapy—
chest wall coupage, tracheal manipulation to 
stimulate mild cough and postural drainage; may 
enhance clearance of secretions; always do 
immediately after nebulization; avoid allowing the 
patient to lie in one position for a prolonged time. 
• Oxygen therapy—as warranted for patients 
with hypoxemia, signs of respiratory distress.
ACTIVITY
Restrict during treatment (inpatient or 
outpatient), except as part of physical therapy 
after aerosolization.
DIET
• Ensure normal intake with food high in protein 
and energy density. • Enteral or parenteral 
nutritional support—indicated in severely ill 
patients. • Use caution in feeding animals with 
megaesophagus, laryngeal dysfunction or surgery, 
pharyngeal disease, or recumbent patients.
Warn client that high morbidity and mortality 
are associated with severe hypoxemia and sepsis.
Lung lobectomy may be required with 
pulmonary abscessation or bronchopulmonary 
foreign body with secondary pneumonia; may 
be indicated if patient is unresponsive to 
conventional treatment and disease is limited 
to one or two lobes.
• Antimicrobials are best selected based on 
results of culture and susceptibility testing from 
tracheal wash or other pulmonary specimens. 
• Empiric antimicrobial therapy is justified when 
there is significant risk in obtaining adequate 
samples or if the time required to culture causes a 
life-threatening delay in treatment. • Recently 
administered antimicrobials should be avoided. 
• Reasonable initial antimicrobial choices 
pending culture results include amoxicillin-
clavulanic acid 15 mg/kg PO q12h or cephalexin 
22–30 mg/kg PO q12h with enrofloxacin (dogs, 10–20 mg/kg q24h; cats, maximum 5 mg/kg 
q24h), or trimethoprim-sulfonamide 15 mg/kg 
PO q12h. • Gram-positive cocci—ampicillin 
20–40 mg/kg IV q6–8h, ampicillin-sulbactam 
22–30 mg/kg IV q6–8h; amoxicillin 22 mg/kg 
PO q12h; amoxicillin-clavulanic acid; 
azithromycin; chloramphenicol, erythromycin; 
trimethoprim-sulfonamide; first-generation 
cephalosporins. • Gram-negative rods—
enrofloxacin or marbofloxacin; cefpodoxime; 
chloramphenicol; trimethoprim-sulfonamide; 
amikacin. • Bordetella —doxycycline 5 mg/kg 
PO q12h; chloramphenicol; enrofloxacin; 
azithromycin. • Mycoplasma —doxycycline, 
enrofloxacin, marbofloxacin, chloramphenicol. 
• Anaerobes—amoxicillin–clavulanic acid; 
chloramphenicol; metronidazole; clindamycin; 
ticarcillin-clavulanic acid. • Antimicrobial 
nebulization for Bordetella —gentamicin 
nebulization 5 mg/kg q24h for 5–7 days, 
typically adjunctive with systemic antimicrobials.
• Authors have traditionally recommended 
continued treatment for at least 10 days beyond 
clinical resolution and/or 1–2 weeks following 
radiographic resolution. • Total of ≤14 days of 
therapy is not associated with worse outcomes 
when compared to >14 days of therapy in dogs.
• Anticholinergics and antihistamines—may 
thicken secretions and inhibit mucokinesis 
and exudate removal from airways. 
• Antitussives—potent, centrally acting 
agents inhibit mucokinesis and exudate 
removal from airways; can potentiate 
pulmonary infection and inflammation.
Avoid use of theophylline and 
fluoroquinolones concurrently.
• Expectorants—recommended by some 
clinicians; no objective evidence that they 
increase mucokinesis or mobilization of 
secretions. • Bronchodilators—recommended 
by some clinicians to alleviate bronchospasm.
  FOLLOW-UP
• Monitor respiratory rate and effort. • Complete 
blood count will normalize. • Arterial blood 
gases—sensitive monitor of progress, pulse 
oximetry can be helpful. • Frequent thoracic 
auscultation. • Thoracic radiographs—improve 
more slowly than the clinical appearance.
• Vaccination—against upper respiratory 
viruses and Bordetella  if a dog is boarded or 
exposed to large numbers of other animals. 
• Catteries—environmental strategies to lower 
population density and improve hygiene help 
control outbreaks of bordetellosis.POSSIBLE COMPLICATIONS
• Sepsis can develop. • Severe respiratory 
compromise may require intubation/
mechanical ventilation.
• Prognosis—good with aggressive antibacterial 
and supportive therapy; more guarded in young 
animals, patients with immunodeficiency, and 
patients that are debilitated or have severe 
underlying disease. • Prolonged infection—
potential for chronic bronchitis or bronchiectasis 
in any patient. • Mortality—associated with 
severe hypoxemia and sepsis.
• Frequently develops secondary to underlying 
functional or anatomic abnormalities—cleft 
palate; tracheal hypoplasia; primary ciliary 
dyskinesia; laryngeal paralysis; megaesophagus 
or other esophageal dysmotility disorder. 
• Bronchiectasis—both predisposing factor 
and potential complication.
• Young puppies and kittens—may have a 
poorer prognosis. • Underlying functional and 
anatomic problems and immunodeficiencies—
suspect in young patients.
Bitches or queens infected with 
B. bronchiseptica —may transmit infection 
to neonates.
Dear JD. Bacterial pneumonia in dogs and 
cats. Vet Clin North Am Small Anim Prac 
2014, 44(1):143–159.
Jameson PH, King LA, Lappin MR, et al. 
Comparison of clinical signs, diagnostic 
findings, organisms isolated, and clinical 
outcome in dogs with bacterial pneumonia: 
93 cases (1986–1991). J Am Vet Med Assoc 
1995, 206:206–209.
Proulx A, Hume DZ, Drobatz KJ, et al. In 
vitro bacterial isolate susceptibility to 
empirically selected antimicrobials in 111 
dogs with bacterial pneumonia. J Vet Emerg 
Crit Care 2013, 24(2):194–200.
Wayne AS, Davis M, Sinnott VB, et al. 
Outcomes in dogs with uncomplicated, 
presumptive bacterial pneumonia treated 
with short or long course antibiotics. Can 
Vet J 2017, 58:610–613.
Author  Ian DeStefano
Melissa A. Herrera. 
available online(continued)  Pneumonia, Bacterial

1088  Blackwell’s Five-Minute Veterinary Consult  
PPneumonia, Eosinophilic
  BASICS
The fully developed inflammatory response to 
antigens in lung parenchyma characterized by 
exudation of eosinophils and fluid into lung 
interstitium, conducting airways, and alveolar 
spaces.
• Immunologic basis—supporting evidence 
generally accepted; mechanisms involved not 
yet clarified. • Eosinophilic infiltration and a 
predominance of CD4+ T-cells in broncho -
alveolar lavage fluid support the role of a 
dominant Th2 immune response in the lower 
airways. • Evolution of disease—likely 
determined by characteristics of antigens, host 
response, and regulation of that response. 
• Antigens enter the lower respiratory tract by 
inhalation or hematogenous routes. • Chronic 
exposure to antigens—elicits a humoral and 
cellular immune response. • Allergic or 
hypersensitivity pulmonary disorders—
associated with an abnormal humoral 
antibody response and a cell-mediated 
immunoregulatory defect. • Immunoglobulin 
classes involved—IgE, IgG, and others. 
• High numbers of activated macrophages 
and T-lymphocytes and depressed suppressor 
T-cell activity—alter cell-mediated immunity. 
• Collagenolytic enzyme activity—increased. 
• Generally referred to as eosinophilic broncho -
pneumopathy although at least three disease 
patterns appear to exist: eosinophilic 
pneumonitis, eosinophilic bronchitis, and 
pulmonary eosinophilic granulomatosis. 
• Severely affected dogs appear to develop 
marked granulomatous disease. • Heartworm 
disease with pneumonitis—microfilaria may 
become entrapped in the pulmonary 
circulation and trigger an immune response. 
• Mortality—associated with severe hypoxemia 
(e.g., low arterial oxygen concentration) and 
(rarely) severe hemoptysis.
• Respiratory—lower respiratory tract 
primarily but nasal cavity can also be 
involved. • Cardiovascular—can develop cor 
pulmonale.
GENETICS
N/A
N/A
Species
Dog
Siberian husky, possibly.Mean Age and Range
All ages but more often young adults (4–6 
years of age).
None
SIGNS
Extremely variable, depending on the severity.
• Cough—unresponsive to antibacterial 
therapy. • Labored breathing. • Exercise 
intolerance. • Anorexia. • Lethargy. • Weight 
loss. • Nasal discharge. • Fever (uncommon).
• Harsh, moist cough. • Tachypnea or 
respiratory distress. • Abnormal breath 
sounds on auscultation—increased-intensity 
breath sounds; crackles; wheezes; decreased 
sounds can occur. • Weight loss. • Yellow-
green or mucopurulent nasal discharge. 
• Fever (uncommon).
CAUSES
• Purported aeroallergens—spores or hyphae 
from fungi and actinomycetes; pollen; insect 
antigens; dust or storage mites; unidentified 
triggers of the immune response. • Parasitic 
antigens—heartworm microfilaria, respiratory 
• Living in a heartworm-endemic area without 
receiving preventive medication. • Dusty or 
moldy environment. • Air pollution.
  DIAGNOSIS
• Parasitic pneumonia—capillariasis; 
paragonimiasis; dirofilariasis. • Fungal 
pneumonia—histoplasmosis; blastomycosis; 
coccidioidomycosis; cryptococcosis. • For 
eosinophilic pneumonitis—bacterial 
pneumonia; viral pneumonia (e.g., canine 
distemper virus and canine adenovirus); 
rickettsial pneumonia (e.g., ehrlichiosis and 
Rocky Mountain spotted fever); protozoal 
pneumonia (e.g., toxoplasmosis); congestive 
heart failure; bartonellosis. • For eosinophilic 
bronchitis—infectious tracheobronchitis; 
chronic bronchitis. • For pulmonary 
eosinophilic granulomatosis—neoplasia 
(including lymphomatoid granulomatosis); 
pulmonary abscess; bronchial foreign body.
• Inflammatory leukogram—neutrophilic 
leukocytosis with or without a left shift, 
eosinophilia, basophilia, or monocytosis. 
• Absence of eosinophilia does not exclude 
diagnosis. • Hyperglobulinemia—suggests 
chronic antigenic stimulus; rule out occult 
dirofilariasis.OTHER LABORATORY TESTS
Arterial Blood Gas Analysis
• Values correlate well with the degree of 
physiologic disruption; sensitive monitor of 
patient’s progress during treatment. 
• Hypoxemia—mild or moderate, Pao2 <80 
mmHg on room air; severe, Pao2 <60 mmHg 
on room air.
Other
• Heartworm microfilaria and antigen 
tests—positive results suggest dirofilariasis or 
eosinophilic pneumonitis associated with 
microfilaria trapped in the lung. Multiple 
tests can be required to rule out disease. 
• Fecal flotation and Baermann sedimentation. 
• Protein electrophoresis— β-globulin spike 
(hyperbetaglobulinemia) often found with 
occult dirofilariasis.
IMAGING
• Radiographic findings depend on extent and 
severity of disease. • Thoracic radiographs— 
help document the severity of pulmonary 
artery disease; reveal interstitial pneumonitis 
in dogs with dirofilariasis. • Eosinophilic 
pneumonitis—linear or miliary interstitial 
pattern that resembles changes seen with early 
pulmonary edema or fungal pneumonia; 
pulmonary densities with indistinct margins 
in severely affected patients; tortuous, large 
pulmonary arteries and right-sided 
cardiomegaly in patients with dirofilariasis. 
• Eosinophilic bronchitis—bronchial pattern 
with thickened bronchi extending into the 
periphery of the lung (tram/railroad track and 
donut signs); bronchiectasis in chronic cases. 
• Eosinophilic granuloma—multiple nodular 
lesions of variable sizes in different lung lobes; 
patchy, focal alveolar densities; tracheo-
bronchial lymphadenopathy possible.
• T ranstracheal or endotracheal wash 
appropriate for sample collection. 
• Bronchoscopy; yellow-green mucus, 
polypoid mucosal proliferation, partial airway 
collapse. Occlusive eosinophilic plaques or 
granulomas sometimes visible within airways. 
• Bronchoalveolar lavage—with or without 
bronchoscope. • Bacterial and mycoplasmal 
culture of bronchoalveolar lavage fluid is 
recommended to rule-out bacterial infection. 
Occasionally, concurrent bacterial infection 
can be identified in dogs with eosinophilic 
lung disease. • Fine-needle lung aspiration 
and examination. • Cytologic examination of 
aspirates, washings, or brushings—definitive 
diagnosis: eosinophilic inflammation 
predominates; may note other types of 
inflammatory cells; carefully examine 
specimens for antigenic sources (e.g., 
parasites, fungi, or neoplasia). • Consider 
intradermal skin or serologic allergen testing—  
rarely may identify allergens. • Fecal

Canine and Feline, Seventh Edition  1089
Pexaminations—routine flotation, direct 
smear, sediment examination, and Baermann 
technique to rule out parasitic pneumonia; 
negative test can occur due to intermittent 
shedding and empirical therapy warranted in 
• Gross—diffuse, patchy, or nodular firm 
lesions; usually pale or mottled. 
• Histopathologic—eosinophilic, lymphocytic, 
and macrophagic infiltration of alveolar walls 
and alveolar spaces; as disease progresses, 
interstitial infiltrative process becomes fibrotic 
with obliteration of alveolar spaces, and 
granulomas can be dispersed within the 
interstitial fibrosis. Upper respiratory tract 
epithelium can also be involved with 
eosinophilic infiltration.
  TREATMENT
signs (e.g., anorexia, weight loss, or lethargy).
• Dehydration—hinders mucociliary 
clearance and secretion mobilization; 
maintain normal systemic hydration with a 
balanced multielectrolyte solution. 
• Supplemental oxygen—for respiratory 
distress.
ACTIVITY
Restricted during treatment (inpatient or 
outpatient).
DIET
Ensure normal intake.
Warn client that morbidity and mortality are 
associated with severe hypoxemia.
Lung lobectomy can be required with large 
granulomas.
• Corticosteroids—prednisolone or 
prednisone at 2 mg/kg/day until clinical signs 
begin to resolve (typically 2–3 weeks); then 
taper slowly (over months). Maintenance 
dosages of prednisone are often required long 
term (0.125–0.5 mg/kg q48h or every 3 or 4 
days for 4–6 months or longer). • Following 
adequate control of disease and/or due to side effects of systemic glucocorticoids, inhaled 
corticosteroids (e.g., fluticasone propionate) 
can be used in conjunction with a spacing 
chamber and facemask. • Antibiotic therapy 
indicated only if active infection documented 
on airway culture. Prophylactic therapy could 
lead to development of antimicrobial 
resistance. • Heartworm adulticidal therapy—
for heartworm-positive patient; initiate after 
the patient has been stabilized with corticos -
teroids and rest. • Itraconazole or 
ketoconazole—use antifungal drugs only if the 
fungal infection is confirmed by cytologic 
examination or culture. • Hyposensitization—
allergy shots based on results of intradermal 
skin or serologic testing can be attempted 
but is not the treatment of choice in most 
patients. Most dogs will still require 
steroid therapy.
N/A
N/A
Other immunosuppressive drugs (e.g., 
cyclosporine)—can use when corticosteroids 
are contraindicated or have been ineffective, 
although inhaled steroids are preferred. No 
trial results are available to date.
  FOLLOW-UP
• Complete blood count will show resolution 
of peripheral eosinophilia or neutrophilia. 
• Arterial blood gases—most sensitive 
monitor of progress. Can remain abnormal 
even with successful management of disease. 
• Auscultate patient thoroughly several times 
daily. • Thoracic radiographs—improve more 
slowly than the clinical appearance.
• Routine heartworm-prevention medication. 
• Consider changing patient’s environment if 
an aeroallergen is suspected.
Pulmonary embolization—dogs treated with 
adulticidal therapy for dirofilariasis.
• Prognosis good for mild-to-moderate 
cases; many patients require long-term 
treatment with steroids. • If allergen can be 
identified and eliminated—suspect improved 
prognosis. • Heartworm infection—prognosis 
depends on severity of pulmonary hypertension, 
cor pulmonale, and embolization. • Eosinophilic granulomatosis—prognosis 
guarded; often disease is progressive.
• Dirofilariasis. • Bronchopulmonary fungal 
N/A
N/A
drugs are relatively contraindicated in 
SYNONYMS
• Allergic alveolitis. • Allergic bronchitis. 
• Bronchitic pulmonary eosinophilia. 
• Eosinophilic bronchitis or 
bronchopneumopathy. • Eosinophilic 
pneumonia/pneumonitis. • Eosinophilic 
pulmonary granulomatosis. • Extrinsic 
allergic alveolitis. • Hypersensitivity 
pneumonitis. • Occult heartworm 
pneumonia. • Parasitic pulmonary 
eosinophilia. • Pulmonary infiltrates with 
SEE ALSO
• Cough.
Clercx C, Peeters D. Canine eosinophilic 
bronchopneumopathy. Vet Clin North Am 
Small Anim Pract 2007, 37:917–935.
Clercx C, Peeters D, German AJ, et al. An 
immunologic investigation of canine 
eosinophilic bronchopneumopathy. J Vet 
Intern Med 2002, 16:229–237.
Clercx C, Peeters D, Snaps F , et al. 
Eosinophilic bronchopneumopathy in dogs. 
J Vet Intern Med 2000, 14:282–291.
Cooper ES, Schober KE, Drost WT. Severe 
bronchoconstriction after bronchoalveolar 
lavage in a dog with eosinophilic airway 
disease. J Am Vet Med Assoc 2005, 
227:1257–1262.
Melissa A. Herrera.(continued)  Pneumonia, Eosinophilic

1090  Blackwell’s Five-Minute Veterinary Consult  
PPneumonia, Fungal
  BASICS
Inflammation of the pulmonary interstitial, 
lymphatic, and peribronchial tissues caused 
by deep mycotic infection.
• Mycelial fungal elements—inhaled from 
contaminated soil or plant debris; organisms 
then colonize the lungs. • Dimorphic fungi 
such as Blastomyces dermatitidis , Histoplasma 
capsulatum , Coccidioides immitis —yeast phase 
at body temperature. Invasive fungal infections 
with Aspergillus  spp. follow inhalation of 
airborne spores with growth as mycelia within 
tissue. • Systemic dissemination of yeast from 
the lungs common in dogs and cats. 
• Pulmonary interstitial and alveolar involve­
ment—can cause hypoxia. • Airway 
involvement—causes cough. • Cell­mediated 
immune response leads to pyogranulomatous 
inflammation. • Pulmonary complications 
include interstitial and/or bronchial 
pneumonia, pleural effusion, mediastinal 
granuloma formation, acute respiratory distress 
syndrome, and pulmonary thromboembolism.
• Depend on the specific fungal disease. 
• Blastomycosis—respiratory involvement in 
∼85% of cases; diffuse interstitial, alveolar, or 
bronchial pneumonia most common; solitary 
mass lesions can be seen, especially in cats; 
tracheobronchial lymphadenopathy can 
contribute to cough; nasal infection rare. 
Multisystemic involvement of skin, lymph 
nodes, eyes, bone, reproductive tract, and CNS 
often seen. • Histoplasmosis—respiratory 
disease alone is only seen in 10% of cases; but 
multisystemic involvement with diffuse 
interstitial pneumonia is common, especially in 
cats; perihilar or mediastinal lymphadenopathy 
contributes to cough. Multisystemic involvement 
of gastrointestinal tract, liver, lymph nodes, 
spleen, bone marrow, eyes, bone, and CNS often 
seen. • Coccidioidomycosis—diffuse interstitial 
or bronchial pneumonia common in dogs but 
less common in cats; perihilar or mediastinal 
lymphadenopathy common. Multisystemic 
involvement of bone, skin, eyes, lymph nodes, 
heart, and CNS often seen. • Cryptococcosis—
nasal cavity involvement most common in cats, 
neurologic system in dogs. Skin and other organs 
also affected. • Systemic aspergillosis—
Aspergillus terreus : pneumonia less common, 
renal and bone (especially vertebral) involvement 
common.
GENETICS
Breed susceptibilities may be related to defects 
in cell ­mediated immunity.
Depends on geographic distribution.GEOGRAPHIC DISTRIBUTION
• Blastomycosis—endemic in US Southeast 
and Midwest along the Mississippi, Ohio, 
Missouri, and Tennessee rivers and southern 
Great Lakes; also in southern Mid ­Atlantic 
States, Pacific Northwest, and southern 
Canada from east coast to prairie regions of 
southern Saskatchewan and Manitoba. 
• Histoplasmosis—similar to but more widely 
distributed than blastomycosis; pockets of 
disease in Texas, Oklahoma, and California. 
• Coccidioidomycosis—US Southwest from 
Texas to California. Northern Mexico and 
parts of South America. • Cryptococcosis and 
aspergillosis—worldwide.
Species
Dog and less commonly cat (except crypto­
coccosis and histoplasmosis where the cat is 
affected more often than dogs).
• Systemic mycosis—large ­breed, sporting, 
working, hunting or field trial dogs; Doberman 
pinschers and Rottweilers appear predisposed 
to disseminated disease. • Systemic 
aspergillosis—German shepherd dogs 
overrepresented. • Cryptococcosis—cocker 
spaniels overrepresented.
• Young animals ( <5 years) predisposed. 
• Any age can be affected.
Males affected 2–4 times more often than 
females.
SIGNS
Multisystemic illness depends on organ 
• Chronic weight loss and inappetence. 
• Oculonasal discharge. • Coughing—can be 
prominent but seen inconsistently even with 
marked pulmonary disease. • Tachypnea or 
exercise intolerance common. • Labored 
breathing—more common in cats; sign of 
severe disease in both dogs and cats. • Acute 
blindness or blepharospasm—if eyes are 
affected. • Papules and cutaneous nodules—
common but often missed until draining 
tracts appear. • Lameness—if bones affected 
or if osteomyelitis develops. • Seizures, ataxia, 
behavior change—if CNS affected.
• Emaciation—in chronically affected 
patients. • Fever—about 50% of patients. 
• Harsh, loud breath sounds, crackles in 
cats, cough on tracheal palpation. 
• Dyspnea—at rest with severe disease. 
• Lymphadenopathy—common in dogs 
with dimorphic fungal infections. 
• Blastomycosis (dogs)—cutaneous and subcutaneous nodules with draining tracts; 
chorioretinitis; granulo  matous retinal 
detachment common. • Coccidioidomycosis 
(dogs)—lameness and pain from osteomyeli ­
tis, pericardial disease; cats—skin lesions. 
• Histoplasmosis (dogs)—emaciation and 
bloody diarrhea; cats—skin lesions. 
• Cryptococcosis—nasal cavity and soft 
tissue infection common in cats; chorioreti ­
nitis in dogs and cats.
CAUSES
• Primary route of infection— Blastomyces 
dermatitidis : lungs, Histoplasma capsulatum : 
lungs and possibly gastrointestinal tract, 
Coccidioides immitis : lungs. • Cryptococcus 
neoformans  and C. gattii —nasal cavity, with 
direct extension into the eyes or CNS, lungs 
(especially in dogs, less often in cats). 
• Aspergillus  spp.—nasal cavity and lungs.
• Blastomycosis, histoplasmosis, and 
cryptococcosis—environmental exposure to 
soils rich in organic matter; blastomycosis and 
cryptococcosis—exposure to bird droppings 
or other fecal matter; blastomycosis—living 
near water. • Coccidioidomycosis—
environmental exposure to sandy, alkaline soil 
after periods of rainfall; outdoor activities 
(hunting and field trials). • Feline leukemia 
virus does not appear to be a risk factor and 
feline immunodeficiency virus may be minor 
risk factor. • Prednisone—may worsen the 
disease. • Antineoplastic chemotherapy. 
• Lymphoreticular neoplasia.
  DIAGNOSIS
• Metastatic neoplasia. • Eosinophilic lung 
disease. • Lymphomatoid granulomatosis. 
• Lymphoreticular and histiocytic neoplasia. 
• Idiopathic pyogranulomatous disease. 
• Feline infectious peritonitis or other 
vasculitic disease. • Parasitic pneumonia. 
• Bacterial pneumonia. • Viral pneumonia. 
• Chronic bronchial disease. • Pulmonary 
edema. • Pulmonary thromboembolism.
• Moderate leukocytosis with or without a 
left shift. • Lymphopenia common. 
• Leukopenia, thrombocytopenia, non ­
regenerative anemia—with histoplasmosis. 
• Hyperglobulinemia and hypoalbuminemia 
common. • Hypercalcemia—occasionally 
(most often in dogs with blastomycosis). 
• Liver enzyme activities—more likely to be 
increased with histoplasmosis. • Urinalysis 
usually normal; proteinuria—occasionally 
seen. • Organisms—rarely can be seen in 
urine (common with Aspergillus ) if kidneys or 
lower urinary tract are affected.

Canine and Feline, Seventh Edition  1091
POTHER LABORATORY TESTS
• Antigen can be detected in serum or urine by 
enzyme immunoassay for diagnosis of Blastomyces  
or Histoplasma —sensitivity and specificity high, 
especially in urine. Cross ­reaction occurs between 
Blastomyces  and Histoplasma . Antigen testing for 
Coccidioides  is insensitive. • Serologic (antibody) 
testing for blastomycosis and histoplasmosis—
false­positive and false ­negative results 
common. Positive titer for Coccidioides  using 
heat­precipitated agar gel immunodiffusion 
consistent with infection with relevant clinical 
history and signs. • Latex agglutination test—  
for capsular antigen; highly reliable for 
cryptococcosis. • Cytologic or histologic 
identification of the organism—definitive 
diagnosis. • Culture—not usually necessary; can 
be difficult to isolate and risky due to zoonosis.
IMAGING
• Thoracic radiography—diffuse interstitial 
(histoplasmosis and coccidioidomycosis) to 
nodular interstitial and peribronchial infiltrates 
(blastomycosis); nodular densities can coalesce 
to granulomatous masses with indistinct edges; 
tracheobronchial lymphadenopathy common; 
large focal granulomas more likely in cats. 
• Appendicular or axial skeleton radiography—  
osteolysis with periosteal proliferation; soft 
tissue swelling. • Abdominal ultrasonography—  
granulomas or large lymph nodes. • Ocular 
ultrasonography—retrobulbar mass, posterior 
uveitis.
• Impression smear or aspirate of a skin nodule—
most likely to yield organisms. • Fine­needle 
lung aspirate—possibly more diagnostic than 
tracheal aspirate or bronchoalveolar lavage 
specimen. • Lymph node aspirate or biopsy. 
• CSF tap—with cryptococcosis. • Bone marrow 
or liver/splenic aspirate—with histoplasmosis. 
• Biopsy—may be needed.
• Pyogranulomatous inflammation. 
• Organisms—usually seen with blastomycosis, 
histoplasmosis, cryptococcosis, and aspergillosis; 
difficult to find with coccidioidomycosis.
  TREATMENT
• Outpatient—if patient is stable. • Inpatient 
evaluation and treatment—dehydration, 
anorexia, and severe hypoxia.
Administration of fluids, oxygen, and anti­
fungals as needed.
DIET
• Feed high ­quality protein, calorically dense 
food. • Histoplasmosis accompanied by 
marked gastrointestinal involvement—feed 
highly digestible food.CLIENT EDUCATION
• Complete response to treatment in <70% 
of dogs and a smaller percentage of cats. 
• Relapse is common. • T reatment is 
expensive and will be long term (>2 months). 
• Clean environmental areas of highly 
organic matter or feces.
Focal granulomas or glaucomatous painful 
eyes can require removal.
• Itraconazole 5–10 mg/kg PO daily; must be 
given with food. Liquid suspension more 
bioavailable in cats (dose 1–1.5 mg/kg/day 
PO). • Fluconazole 10 mg/kg PO q12h; drug 
of choice for cryptococcosis and patients with 
CNS or urinary tract involvement. Usually 
requires longer treatment. • Lipid ­complex 
amphotericin B 1–2 mg/kg IV q48h for 12 
treatments; nephrotoxicity low; diuresis not 
required. • Posaconazole 5 mg/kg PO q24h 
with food may be more effective for 
Corticosteroids are relatively contraindicated 
but may be required to reduce inflammation 
during initial treatment in severely dyspneic 
patients or patients with CNS disease.
• Azole drugs—do not use with severe liver 
disease. • Amphotericin B—do not use in 
azotemic or dehydrated patients; stop use if 
BUN >50 mg/dL or creatinine >3 mg/dL. 
• Itraconazole and the other azole drugs—
anorexia; increase in liver enzymes; cutaneous 
Antacids and anticonvulsants—can lower 
blood concentration of itraconazole.
• Ketoconazole 10–30 mg/kg PO q12h; can 
be effective; higher incidence of side effects; 
longer treatment is necessary; relapse 
common. • Amphotericin B 0.5 mg/kg 
(dogs) or 0.25 mg/kg (cats) IV three times/
week to a total dose of 8 mg/kg if used alone 
or 4 mg/kg if used with an azole drug; 
administer in 200–500 mL of D5W after 
saline diuresis; best used with itraconazole or 
ketoconazole for severely affected patients. 
• Amphotericin B—alternative: 0.5–0.8 mg/kg 
2–3 times per week; to reduce nephrotoxicity, 
can give subcutaneously diluted in 0.45% 
saline/2.5% dextrose solution (400 mL for 
cats, 500 mL for dogs <20 kg, 1,000 mL for 
dogs >20 kg). • Voriconazole 3–4 mg/kg PO 
q12h for invasive aspergillosis; causes CNS 
signs in cats. • Terbinafine 30–40 mg/kg PO q12h can be added to azole treatment regimes 
in resistant infections. • Nikkomycin Z 250 
mg PO q12h for dogs 5–15 kg; 500 mg PO 
q12h for dogs >15 kg for treatment of 
coccidioidomycosis.
  FOLLOW-UP
• Liver enzymes—evaluated monthly during 
azole therapy. • BUN and creatinine—
measure before each dose of amphotericin B. 
• Thoracic radiographs—reevaluate before 
discontinuing treatment. • Urine antigen 
testing for Blastomyces /Histoplasma —use to 
monitor therapy.
Reduce possible exposure.
• Blindness is usually permanent. • Renal 
failure from amphotericin B.
• Blastomycosis—requires a minimum of 2 
months of treatment; 60–70% of dogs cured 
by itraconazole. Dogs with dyspnea or 
hypoxemia have poorer prognosis. 
• Histoplasmosis, coccidioidomycosis—
continue at least 1 month past remission 
(usually 6 months or more). • Systemic 
aspergillosis—poor prognosis. • Relapse—
can occur up to 1 year after treatment.
Young animals predisposed.
Infections in people—primarily from a 
common environmental source; no direct 
transmission from animals to humans, except 
by penetrating wounds contaminated by the 
organism; needle stick injury.
• Fungal abortion possible. • Azole 
antifungals—teratogenic; do not use in 
SEE ALSO
• Aspergillosis, Nasal. • Blastomycosis. 
Author  Joseph Taboada
available online(continued)  Pneumonia, Fungal

1092  Blackwell’s Five-Minute Veterinary Consult  
PPneumonia, Interstitial
  BASICS
A form of pneumonia in which the inflam-
matory process occurs in alveolar walls and 
interstitial space.
• Results from either aerogenous injury to the 
alveolar epithelium (type I or II pneumocytes) 
or hematogenous injury to the alveolar 
capillaries; may be triggered by infectious 
agents. • Alveolar wall damage often occurs 
secondary to inflammation and antigen–
antibody complex deposition. • Progression 
from acute to chronic interstitial pneumonia 
can occur leading to alveolar fibrosis ± 
interstitial mononuclear cell accumulation and 
persistent type II pneumocyte hyperplasia.
• Respiratory. • Cardiovascular (if cor 
pulmonale develops).
GENETICS
Idiopathic pulmonary fibrosis (IPF) is 
breed-associated (West Highland white 
terriers/terrier breeds); a definitive genetic 
defect is not known.
Incompletely understood.
• Infectious organisms: Aelurostrongylus 
abstrusus —Europe, United States, Australia. 
• Angiostrongylus vasorum —Europe, Africa, 
South America, North America. • Leishmania 
chagasi —South and Central America. 
• H3N2/H3N8—China, USA. Pneumocystis 
and toxoplasmosis—worldwide.
• Canine distemper virus—dogs 3–6 
months of age. Greyhounds, Siberian 
huskies, Weimaraners, Samoyeds, and 
Alaskan Malamutes overrepresented. 
• Endogenous lipid pneumonia (EnLP)—
older cats of either sex. • Pulmonary 
interstitial lung disease—middle- to old-  
aged West Highland white terrier, ± Cairn 
terriers and bull terriers. • Feline IPF-like 
disease—middle-aged to older cats. 
• Pneumocystis jirovecii —miniature 
dachshunds <1 year of age at risk, cavalier 
King Charles spaniels, any immunocompromised 
dog. • Toxoplasmosis—middle-aged male cats.
SIGNS
Depends on severity of disease.
Tachypnea, coughing, respiratory difficulty, 
exercise intolerance.Physical Examination Findings
• Open-mouth breathing, end-inspiratory 
and early expiratory crackles, orthopnea, 
cyanosis, ± hemoptysis. • Animals with 
paraquat toxicity often display vomiting, 
oliguria, diarrhea, and oropharyngeal ulcers 
(± hyperexcitability and neurologic signs in 
the early phase). • Retinitis, uveitis, neuro -
logic signs, and/or gastrointestinal signs can 
be seen with toxoplasmosis.
CAUSES
• Congenital—bronchiolitis obliterans with 
organizing pneumonia (BOOP) secondary to 
primary ciliary dyskinesia. • Metabolic—
uremic pneumonitis ± BOOP , hepatic disease, 
or pancreatitis in cats. • Neoplastic—
bronchiectasis or BOOP , pulmonary 
carcinoma associated with pulmonary fibrosis 
in cats. • Idiopathic—pulmonary interstitial 
fibrosis and desquamative interstitial 
pneumonitis (DIP), some cases of EnLP , 
BOOP , primary pulmonary alveolar 
proteinosis (PAP). • Inflammatory—EnLP 
most common in cats with bronchitis, 
bronchiectasis or necrotizing bronchiolitis. 
• Infectious—Dogs: canine distemper virus, 
canine adenovirus-2, H3N2 or H3N8 
influenza virus, Leishmania chagasi , 
Pneumocystis jirovecii , Angiostrongylus vasorum , 
Mycoplasma  sp, Toxoplasma, Leptospirosis, 
Babesia  sp, Ehrlichia canis . Cats: 
Aelurostrongylus abstrusus , Toxoplasma , feline 
immunodeficiency virus, influenza virus 
(anthroponotic transmission described). 
• Toxic—inhalation of dusts, gases, or vapors, 
thiacetarsamide, aspiration of petroleum-based 
products in cats, secondary PAP , paraquat 
toxicity, silicosis, asbestosis. • Vascular—
thromboembolism, circulating larval migrans.
• Immunosuppression, inadequate vaccination 
or preventative, and exposure to other animals 
can predispose to viral or parasitic pulmonary 
disease. • Inhalation of toxic material or gases 
may predispose to pulmonary fibrosis.
  DIAGNOSIS
• Airway disease. • Bronchopneumonia. 
• Heartworm disease. • Embolic pneumonia. 
• Granulomatous pneumonia. • Neoplasia. 
• Neutrophilia, eosinophilia, lymphocytosis, 
hyperglobulinemia possible; polycythemia if 
chronically hypoxemic. • Thrombocytopenia 
with Angiostrongylus vasorum . • Neutropenia or 
high liver enzymes and hyperbilirubinemia 
possible with Toxoplasma . • High liver enzymes 
and hyperbilirubinemia (dogs only) possible with hepatotoxicity due to thiacetarsemide 
therapy ± paraquat toxicity. • Severe azotemia 
and isosthenuria with uremic pneumonitis.
• Arterial blood gas measurement and 
calculation of alveolar–arterial (A-a) gradient 
to assess degree of respiratory impairment; 
Pao2 <80 mmHg indicates hypoxemia, A-a 
gradient >15 is abnormal. • Serologic and 
other tests for infectious causes. • Fecal 
Baermann examination for Aelurostrongylus 
abstrusus  or Angiostrongylus vasorum . 
• Toxicologic analysis of the urine or serum 
to diagnose paraquat toxicity in live animals. 
• Coagulation testing with Angiostrongylus . 
• Immunodiagnostic testing for exposure to 
Leishmania .
IMAGING
Thoracic Radiographic Findings
• A focal or diffuse, mild to severe interstitial to 
bronchial to alveolar pattern can be present, 
dilated bronchi with bronchiectasis or BOOP . 
• Right heart ± PA enlargement and hepatos -
plenomegaly if secondary pulmonary hyper -
tension. • Pleural effusion occasionally seen.
CT
CT characteristics include ground-glass 
opacification, peribronchovascular thicken-
ing, and parenchymal banding.
• Electrocardiography—arrhythmias can 
occur with severe hypoxia or systemic disease. 
• Open lung biopsy required for definitive 
diagnostic test. • Endotracheal or transtracheal 
wash, bronchoscopy with bronchoalveolar 
lavage, and/or fine-needle aspirate of lungs 
might be useful (e.g., may visualize 
trophozoite or cysts of Pneumocystis jirovecii  
or Toxoplasma  or see L1 larvae with 
Aelurostrongylus abstrusus or Angiostrongylus 
vasorum ); cultures can reveal secondary 
bacterial infections. Viral testing (serology or 
swab). With PAP , an opaque white material is 
retrieved from airway wash. • Echocardiogram 
can document pulmonary hypertension.
• Aelurostrongylus abstrusus —greenish nodules 
in lungs, eggs and larvae in the alveolar spaces 
with foreign body type reaction (surrounded 
by mononuclear cells and giant cells), 
submucosal gland hypertrophy, and smooth 
muscle hypertrophy in airway and vessel 
walls. • Angiostrongylus vasorum —
thrombosing arteritis and fibrotic peribronchitis, 
parasites in arterioles. • BOOP—polypoid 
plugs of loose, fibrous tissue fill bronchioles 
and alveoli, foamy macrophages within 
alveoli, variable inflammatory infiltrate with 
type II pneumocyte reactivity. • Interstitial 
lung disease in the West Highland white 
terrier—diffuse, mature pulmonary fibrosis 
(most common in caudal lung lobes),

Canine and Feline, Seventh Edition  1093
P
multifocal areas of accentuated subpleural and 
peribronchiolar fibrosis, thickening of the 
alveolar septum due to excess collagen in the 
extracellular matrix. • IPF-like disease in the 
cat lacks inflammation and may be associated 
with pulmonary carcinoma. Typical changes 
include multifocal distribution of interstitial 
fibrosis with foci of fibroblast/myofibroblasts, 
alveolar epithelial metaplasia, and interstitial 
smooth muscle metaplasia/hyperplasia. 
• Leishmania chagasi  is characterized by 
chronic and diffuse interstitial pneumonitis 
and thickened interalveolar septae in some 
cases. • Lipid pneumonias—macroscopic 
lesions can include subpleural, parenchymal, 
or perivascular white, firm nodules. Mixed 
pattern of inflammation with accumulation 
of lipid-laden macrophages, cholesterol clefts, 
and multinucleated giant cells. • Paraquat 
toxicity—lungs are heavy, edematous, and 
hemorrhagic. Emphysematous bullae and 
pneumomediastinum are commonly present. 
• PAP—alveolar spaces are distended with a 
periodic acid–Schiff staining eosinophilic 
proteinaceous material. Intra-alveolar 
cholesterol clefts and mucus-laden macrophages 
with mild mixed inflammatory infiltrates are 
common. • Uremic pneumonitis—pulmonary 
edema and calcification of smooth muscle 
and/or alveolar walls.
  TREATMENT
Inpatient care and monitoring for animals 
with evidence of respiratory distress.
• Oxygen therapy. • Minimize exposure to 
house dust, vapors, chemical fumes, or 
tobacco smoke. • Humidification of inspired 
air. • PAP—therapeutic bronchoalveolar 
lavage. • Antimicrobial therapy—as 
indicated by results of culture and 
susceptibility.
ACTIVITY
• Exercise restriction as needed. • Harness 
preferred to collar.
DIET
Weight loss if obese.
Palliative care employed.
Definitive diagnosis of interstitial lung disease 
requires histopathology; it is best preceded by 
CT to determine an appropriate site for 
biopsy.  MEDICATIONS
• Inhaled corticosteroids (e.g., fluticasone, 
1 puff q12h) using a spacing chamber and 
facemask. • Bronchodilators can be helpful in 
reducing respiratory effort: extended-release 
theophylline (dog, 10 mg/kg PO q12h; cat, 
15–19 mg/kg q24h in the evening), terbutaline 
sulfate (dog or cat, 0.01 mg/kg SC, IM, or IV 
q8–12h). Inhaled bronchodilators can also be 
used. • Aelurostrongylus abstrusus —
fenbendazole 50 mg/kg PO q24h for 14 days 
(off-label), ivermectin (400 μg/kg SC twice at 
a 3-week interval), or spot-on selamectin 45 
mg (once). • Angiostrongylus vasorum —
levamisole 20–40 mg/kg PO q48h for 5 
treatments ± aspirin ± corticosteroids. 
Alternative therapies include fenbendazole, 
mebendazole, and ivermectin. • BOOP—
corticosteroid use has been reported. • IPF—
no effective therapy. Anti-inflammatory steroid 
therapy with prednisolone (0.5–1 mg/kg PO 
q24–48h often used) and bronchodilators, 
antitussives, or antibiotics if indicated. 
Pirfenidone not yet investigated. • Leishmania 
chagasi —meglumine antimonate 100 mg/kg 
IV or SC q24h for 3–4 weeks or sodium 
stibogluconate 30–50 mg/kg IV or SC q24h 
for 3–4 weeks. • Paraquat toxicity—vomition 
and activated charcoal therapy is indicated if 
recent ingestion is known. Supportive care, 
diuresis using furosemide (most effective in the 
first 3 days following ingestion), ± immuno -
suppressive dexamethasone, cyclophosphamide, 
nicotinamide, superoxide dismutase, and 
vitamin A.
Immunosuppressive therapy can exacerbate 
  FOLLOW-UP
• Have owners observe clinical response to 
therapy, monitor respiratory rate and effort. 
• Repeat physical examination/chest 
auscultation, chest radiographs, lab test, and 
arterial blood gas analysis as indicated.
• Avoid proximity to toxic fumes or paraquat.
• Vaccinate and deworm animals. • Appropriate 
insect and rodent control. Avoid ingestion by 
pets of frogs, lizards, rodents, and birds.
• Secondary pulmonary infections possible.• Pulmonary hypertension can develop.
• Guarded to poor with interstitial 
pneumonia caused by infectious agents or 
uremic pneumonitis. • Poor long-term 
prognosis with IPF (mean survival time is 17 
months in dogs and 5.5 months in cats). 
• Paraquat toxicity—commonly fatal in dogs.
Pulmonary carcinoma—associated with IPF 
in cats.
Young, free-roaming animals are more likely 
to succumb to infectious diseases.
Toxoplasmosis, if animal is shedding oocysts.
T ransplacental infection with Toxoplasma  and 
canine distemper virus is possible.
SEE ALSO
• Bronchiectasis. • Canine Distemper. 
• Canine Infectious Respiratory Disease. 
Infection. • Leishmaniosis. • Toxoplasmosis.
• BOOP = bronchiolitis obliterans with 
organizing pneumonia. • DIP = 
desquamative interstitial pneumonitis. 
• EnLP = endogenous lipid pneumonia. 
• IPF = idiopathic pulmonary fibrosis. • PAP 
= pulmonary alveolar proteinosis.
Cohn LA, Norris CR, Hawkins EC, et al. 
Identification and characterization of an 
idiopathic pulmonary fibrosis-like condition 
in cats. J Vet Intern Med 2004, 
18(5):632–641.
Corcoran BM, Cobb M, Martin WS, et al. 
Chronic pulmonary disease in West 
Highland white terriers. Vet Rec 1999, 
144:611–616.
Heikkilä HP , Lappalainen AK, Day MJ, et al. 
Clinical, bronchoscopic, histopathologic, 
diagnostic imaging, and arterial oxygenation 
findings in West Highland white terriers 
with idiopathic pulmonary fibrosis. J Vet 
Intern Med 2011, 25(3):433–439.
available online(continued)  Pneumonia, Interstitial

1094  Blackwell’s Five-Minute Veterinary Consult  
PPneumothorax
  BASICS
• Air accumulation in the pleural space 
(traumatic or spontaneous).
• Closed pneumothorax—no defects in the 
thoracic wall.
• Open pneumothorax—defect in the 
thoracic wall
• Tension pneumothorax—pleural pressure in 
a closed pneumothorax exceeds atmospheric 
pressure created by unidirectional transfer of 
air into the pleural space.
• The pleural space is a potential space 
between the visceral and parietal pleura 
containing a thin layer of fluid that 
contributes to “tethering” of the lungs to the 
• Closed pneumothorax—air leakage from 
the pulmonary parenchyma, large airway, or 
esophagus.
• Tension pneumothorax—typically due to a 
pleural or pulmonary flap-like defect that 
opens on inspiration to allow leakage of air 
into the pleural space and closes during 
expiration. Development of high intrathoracic 
pressure can cause cardiovascular collapse.
• Open pneumothorax—pleural pressure equals 
atmospheric pressure, leading to lung collapse.
• Spontaneous pneumothorax—associated 
with underlying pulmonary disease that 
ruptures, allowing air leakage.
• Pneumothorax is usually bilateral disease 
due to mediastinal fenestrations.
T raumatic pneumothorax occurs in >40% 
of cases with chest trauma and 11–18% of 
dogs and cats presented for vehicular 
trauma. Pneumothorax has been reported in 
25% of cases with intrathoracic grass awns 
and 70% of dogs with thoracic bite wounds.
Species
Spontaneous pneumothorax—more common 
in large, deep-chested dogs. Siberian huskies 
may be overrepresented.
SIGNS
• T raumatic—recent trauma, thoracocentesis, 
jugular venipuncture, lung aspirate, thoracotomy, 
mechanical ventilation, neck surgery, recent 
endotracheal intubation.
• Spontaneous—possible history of 
pulmonary disease; usually acute.Physical Examination Findings
• Respiratory distress (tachypnea, increased 
respiratory effort, ± orthopnea).
• Shallow, rapid abdominal breathing.
• Decreased to absent breath sounds dorsally.
Traumatic Pneumothorax
• Signs of trauma (blunt or penetrating 
thoracic wall injury) or hypovolemic shock 
(pale mucous membranes, prolonged capillary 
refill time, altered mentation, poor pulse 
quality, tachycardia, decreased extremity 
compared to core temperature).
• Subcutaneous emphysema in some cases with 
pneumomediastinum and/or tracheal trauma.
CAUSES
• T raumatic—blunt trauma, penetrating 
thoracic or cervical injuries, post-thoraco -
centesis or thoracotomy, esophageal 
perforation, endotracheal tube-associated 
tracheal trauma, mechanical ventilation, 
pulmonary aspirate.
• Spontaneous—bullous emphysema (most 
common in dogs), pulmonary bullae or bleb.
• Migrating pulmonary foreign body, 
pulmonary neoplasia, pulmonary abscess, 
feline asthma, bronchopneumonia, mycotic 
pulmonary granuloma, parasitic pulmonary 
disease ( Paragonimus ), congenital pulmonary 
cyst, congenital lobar emphysema, secondary 
to lung lobe torsion.
• Extension of pneumomediastinum.
• T rauma.
• Thoracocentesis.
• Thoracotomy.
• Overinflation of endotracheal cuff.
• Excessive airway pressure during 
• Pulmonary disease/pathology.
• Migrating grass awns.
  DIAGNOSIS
• Diaphragmatic hernia.
• Pulmonary parenchymal disease.
Neutrophilia with a left shift if infection or 
• Arterial blood gases—hypoxemia; 
hypocapnia or hypercapnia.
• Fecal sedimentation or zinc sulfate flotation 
for Paragonimus kellicotti .
IMAGING
• Delay until patient is stable.• Air in pleural space, pulmonary vascular 
pattern does not extend to the chest wall, 
cardiac silhouette elevated off the sternum.
• Pulmonary pathology can be obscured by 
lung lobe collapse.
• T raumatic pneumothorax—pulmonary 
contusions, rib fractures, diaphragmatic 
hernia, hemothorax, foreign bodies.
• Spontaneous pneumothorax—evaluate for 
any sign of parenchymal pathology.
• Right lateral horizontal beam results in the 
highest rate of detection and severity 
gradation while ventrodorsal/dorsoventral 
views have the lowest rate.
Thoracic Ultrasound
• Pneumothorax evidenced by loss of the 
“glide sign.”
• Reverse sliding sign has a 100% specificity 
for detecting mild pneumothorax.
• Sensitivity of 78% and specificity of 93% 
compared to thoracic radiographs in identi -
fication of traumatic pneumothorax in dogs 
with higher sensitivity in penetrating trauma 
(93%) compared to blunt trauma (65%).
• CT has a higher diagnostic yield for 
detecting pneumothorax than thoracic-focused 
assessment with sonography for trauma.
Thoracic CT
• Used preoperatively to improve localization 
of pulmonary pathology in cases with 
spontaneous pneumothorax.
• CT can fail to detect pulmonary bullae 
prior to surgical exploration.
• Bronchoscopy—consider if evidence of 
tracheal or large airway trauma.
• Varies depending on underlying disease.
• Gross evaluation—pulmonary blebs, 
pulmonary or airway tears, pulmonary 
parenchymal disease or masses.
• Histopathology—blebs are most commonly 
found at the apex and are contained entirely 
within the pleura; bullae are lined by pleura, 
fibrous pulmonary tissue, and 
emphysematous lung.
  TREATMENT
• Inpatient care until air accumulation has 
stopped or has stabilized.
• Thoracocentesis in patients with respiratory 
distress—can be performed with an IV 
catheter attached to an extension set and 
stopcock or via a butterfly needle.
• Always  provide oxygen therapy until patient 
is stabilized.
• If large open chest wound—chest tube 
placement, cover with sterile airtight bandage; 
surgical closure once animal is stable.

Canine and Feline, Seventh Edition  1095
P• T ube thoracostomy—use if unable to 
stabilize with thoracocentesis or repeated 
thoracocentesis required for continued 
pneumothorax. A Seldinger technique allows 
chest tube placement under light sedation 
and may be preferable over other thoraco -
stomy tube placement techniques.
• If pneumothorax is rapidly accumulating—
use continuous chest tube suction via one-, 
two- or three-bottle drainage system with an 
underwater seal. If pneumothorax is not 
severe—use intermittent tube aspiration.
• Emergency thoracotomy in life-threatening 
• Open traumatic pneumothorax—surgery as 
soon as patient is stable.
• Closed traumatic pneumothorax—rarely 
requires surgical intervention.
• Spontaneous pneumothorax—early surgical 
intervention recommended in dogs (consider 
median sternotomy), ± pleural access port 
placed for medical management.
• Blood pleurodesis may be of benefit in 
refractory cases—blood is collected from the 
jugular vein and injected into the pleural 
cavity via a thoracostomy tube.
• Appropriate pain control.
• Chest tube maintenance—ensure all 
connections are airtight (cable ties for 
securing connections); ensure the tube is 
attached at two points. Clean tube site and 
change dressing once daily.
ACTIVITY
Strict rest for at least a week following 
• T raumatic pneumothorax—discuss possibility 
of a chest tube, hospitalization; ± surgery.
intervention. Discuss possibility of underlying 
pulmonary disease that can make resolution 
challenging and recurrence possible. Warn 
owner that even with thoracotomy, the source 
of the pneumothorax may not be found and 
recurrent disease is possible.
• Do not use positive-pressure ventilation for 
closed pneumothorax. Place chest tube prior 
to ventilation or await thoracotomy prior to 
• Thoracoscopy—may allow visualization of 
local lesion; allows instillation of substances 
for pleurodesis.• Thoracotomy—if lesion is not evident, can 
fill thorax with saline and look for bubbles as 
sign of a leak. Partial or full lung lobectomy 
for localized lesions. Place thoracostomy tube.
• Pleurodesis with mechanical abrasion of the 
pleura or instillation of an inflammatory 
substance, such as talc, into the pleural space 
(success rate poor).
• Autologous blood-patch for persistent 
pneumothorax (simple and relatively safe 
procedure) in patients that have failed 
conservative or surgical management.
Judicious use of pain control.
Beware excess respiratory depression with opiates.
  FOLLOW-UP
• Respiratory rate—increased rate suggests 
• Serial thoracic radiographs to quantitate 
accumulation of air.
• Pulse oximetry and arterial blood gases may 
be considered.
• Central venous (jugular) blood gases to 
evaluate ventilation status ( Pvco2).
• Rate of air production from chest tube.
Keep pets confined—less likely to be injured.
• Death from hypoxemia and cardiovascular 
• Incorrect placement of chest tube or trauma 
associated with thoracocentesis—lung lobe 
laceration, cardiac puncture, diaphragmatic 
laceration, liver trauma.
• Pleural infection from thoracocentesis or 
thoracostomy tube. The risk of pyothorax 
associated with thoracostomy tube is higher 
between 4 and 6 days after placement.
• T raumatic pneumothorax—good prognosis 
with mild trauma ± chest drain placement. 
Guarded prognosis with severe trauma usually 
because of severe pulmonary contusions.• Spontaneous pneumothorax—prognosis 
depends on underlying cause. Good prognosis 
with focal lesion amenable to surgical 
resection. Poor prognosis with multiple 
lesions or neoplasia.
SYNONYMS
Punctured lung.
SEE ALSO
Lisciandro GR, Lagutchik MS, Mann KA, 
et al. Evaluation of a thoracic focused 
assessment with sonography for trauma 
(TFAST) protocol to detect pneumothorax 
and concurrent thoracic injury in 145 
traumatized dogs. J Vet Emerg Crit Care 
2008, 18:258–269.
Oppenheimer N, Klainbart S, Merbl Y, et al. 
Retrospective evaluation of the use of 
autologous blood-patch treatment for 
persistent pneumothorax in 8 dogs 
(2009–2012). J Vet Emerg Crit Care 2014, 
24:215–220.
Puerto DA, Brockman DJ, Lindquist C, 
Drobatz K. Surgical and nonsurgical 
management of and selected risk factors for 
spontaneous pneumothorax in dogs: 64 
cases (1986–1999). J Am Vet Med Assoc 
2002, 220:1670–1674.
Reetz JA, Caceres AV, Suran JN, et al. 
Sensitivity, positive predictive value, and 
interobserver variability of computed 
tomography in the diagnosis of bullae 
associated with spontaneous pneumothorax 
in dogs: 19 cases (2003–2012). J Am Vet 
Med Assoc 2013, 243:244–251.
Scheepens ET, Peeters ME, L ’Eplattenier HF , 
Kirpensteijn J. Thoracic bite trauma in 
dogs: A comparison of clinical and 
radiological parameters with surgical results. 
J Small Anim Pract 2006, 47:721–726.
Authors  Laura Cagle and Kate Hopper
Consulting Editor  Elizabeth Rozanski 
available online(continued)  Pneumothorax

1096  Blackwell’s Five-Minute Veterinary Consult  
PPododermatitis
  BASICS
An inflammatory, multifaceted complex of 
diseases that involves the feet of dogs and 
cats.
• Depends on the underlying cause. 
• Psychogenic dermatosis (rare cause).
• Dogs—common. • Cats—uncommon.
• Dogs, short-coated breeds—most 
commonly affected; English bulldog, Great 
Dane, basset hound, mastiff, bull terrier, 
boxer, dachshund, Dalmatian, German 
shorthaired pointer, and Weimaraner. • Dogs, 
long-coated breeds—German shepherd dog, 
Labrador retriever, golden retriever, Irish 
setter, and Pekingese. • Cats—none.
• Any age. • Young dogs—hypersensitivity, 
demodicosis, infection, follicular cysts, 
autoimmune dermatoses. • Old dogs—also 
neoplasia or systemic diseases.
• Dogs—male. • Cats—none.
SIGNS
History and physical findings vary 
considerably depending on the underlying 
cause.
• Environment and general husbandry—indoor 
vs. outdoor, working dog, unsanitary conditions, 
contact irritants, hookworms. • Age of onset. 
• Seasonality—atopic dermatitis, allergic 
contact dermatitis, or irritant contact dermatitis. 
• Lesions elsewhere on the body or confined to 
just the feet; note which feet are affected and 
what parts of the feet are affected (entire foot, 
one area, or one digit). • Response to previous 
therapy—antibiotics, antifungals, and 
corticosteroids. • Diet, travel history, and other 
medical problems.
Infectious (Dogs)
• Erythema and edema, nodules, 
inflammatory plaques (fungal “kerions”), 
ulcers, fistulae, hemorrhagic bullae, or 
serosanguineous or seropurulent discharge. 
• Feet—may be grossly swollen; often 
interdigital swellings that have a history of 
opening and draining, may have pitting 
edema of the metacarpal and metatarsal areas. • Skin—may be alopecic and moist from 
constant licking; patient may have some 
degree of pain, pruritus, and paronychia. 
• Regional lymph nodes may be enlarged.
Infectious (Cats)
• Painful paronychia, involving one or more 
claws. • Higher incidence of nodular, often 
ulcerated lesions, compared to dog. 
• Footpads and periungual areas—commonly 
involved. • Interdigital spaces—seldom 
affected. • Scaly and crusted lesions—
occasionally seen.
Allergic (Dogs)
• Salivary staining, erythema and alopecia 
(dorsal or ventral or both) secondary to pruritus; 
dorsal surfaces may be more severely affected 
than ventral surfaces. Hypersensitivities typically 
do not produce draining tracts. • Interdigital 
erythema. • Allergic contact dermatitis—
uncommon; ventral interdigital surfaces most 
affected.
Allergic (Cats)
• Single or multiple, exudative or ulcerated, 
pruritic plaques of the digits, periungual, and 
interdigital spaces. • Eosinophilic granuloma 
complex lesions.
Immune-Mediated (Dogs)
• Crusts and ulcerations—most common 
lesions; occasional vesicles or bullae. • All feet 
affected, especially the ungual folds and 
footpads. • Hyperkeratotic and erosive 
dermatitis of the footpad margins—common 
finding in pemphigus foliaceus.
Immune-Mediated (Cats)
• Lesions—generally involve the footpad, 
including hyperkeratosis and ulceration. 
• Lameness and paronychia with ungual fold 
exudate.
Endocrine/Metabolic (Dogs)
• Lesions—usually consistent with secondary 
infection. • Hepatocutaneous syndrome 
(superficial necrolytic dermatitis)—rare 
condition; skin disease precedes the onset of 
signs of internal disease; hyperkeratosis (with 
adherent crusts), fissures, and ulceration of 
the footpads. • Metastatic calcinosis cutis—
seen with chronic renal disease; painful 
swollen footpads that ulcerate/discharge 
chalk-like material.
Endocrine/Metabolic (Cats)
• Cutaneous xanthomatosis—seen with 
diabetes mellitus; whitish nodules resembling 
candle wax. • Metastatic calcinosis cutis—
• Dogs—nodules, variably ulcerated, scale, 
erythema, depigmentation of the footpads; 
may have only one digit involved (clawbed 
carcinoma, ungual keratoacanthoma); 
multiple feet involvement with clawbed squamous cell carcinoma, epitheliotropic 
lymphoma; pruritus variable. • Cats—
nodules; variably ulcerated and painful; 
localized destruction variable, depends on 
tumor type foot pad tumors may develop de 
novo or be metastatic carcinoma.
Environmental (Dogs and Cats)
• Involve one digit or foot (foreign body, 
trauma) or multiple digits (irritant contact 
dermatitis, thallium toxicity, housing on 
rough surface or in moist environment). 
• Chronic interdigital inflammation, 
ulceration, pyogranulomatous abscesses, 
draining tracts, or swelling, with or without 
pruritus.
• Hyperkeratosis of the footpads (dogs)—
associated with several diseases (e.g., zinc-
responsive dermatosis), and idiopathic digital 
hyperkeratosis. • Interdigital follicular cysts—
interdigital nodules, fistulae and draining tracts 
dorsally; most often affects the lateral inter -
digital space of the front feet; history of 
recurrence and poor to no response to 
antibiotics, with an area of alopecic, thickened 
skin with comedones ventrally. • Nodules 
without draining tracts (dogs)—associated 
with sterile pyogranuloma in several breeds 
and nodular dermatofibrosis of German 
shepherd dogs and golden retrievers. 
• Hypomelanosis of the footpads (cats)—
associated with vitiligo. • Hypermelanosis of 
the footpads (cats)—associated with lentigo 
simplex. • Acral mutilation and analgesia—
seen in pointers (English and German 
shorthaired) and spaniels (English springer and 
French)—cause unknown; often runts of the 
litter; no known treatment; dogs are usually 
euthanized within days to months of diagnosis.
CAUSES
• Bacterial— Staphylococcus pseudintermedius , 
Pseudomonas  spp., Proteus  spp., Mycobacterium  
spp., Nocardia  spp., Actinomyces  spp. 
• Fungal—dermatophytes, intermediate 
mycoses (sporotrichosis, mycetoma), deep 
mycoses (blastomycosis, cryptococcosis). 
• Parasitic— Demodex canis , Pelodera 
strongyloides , hookworms. 
• Protozoal—leishmaniasis.
• Bacterial—same as dog; Pasteurella  spp. 
• Fungal—same as dog, excluding 
blastomycosis. • Parasitic— Neotrombicula 
autumnalis , Notoedres cati , Demodex  spp. 
• Protozoal— Anatrichosoma cutaneum .
Allergic
• Dogs—atopy; food hypersensitivity; allergic 
contact dermatitis. • Cats—atopy; rare for 
flea allergic dermatitis, food hypersensitivity, 
or contact dermatitis to involve paws (except 
lesions of eosinophilic granuloma complex).

Canine and Feline, Seventh Edition  1097
PImmune-Mediated
• Dogs—pemphigus foliaceus; systemic lupus 
erythematosus; erythema multiforme; cold 
agglutinin disease; pemphigus vulgaris; bullous 
pemphigoid; epidermolysis bullosa acquisita, 
symmetrical lupoid onychodystrophy. 
• Cats—pemphigus foliaceus; systemic lupus 
erythematosus; erythema multiforme; 
vasculitis; cold agglutinin disease; plasma cell 
pododermatitis.
Endocrine/Metabolic
• Dogs—hypothyroidism; hyperadreno -
corticism; hepatocutaneous syndrome; chronic 
renal failure. • Cats—hyperthyroidism; 
hyperadrenocorticism; cutaneous xanthomatosis 
(secondary to diabetes mellitus); chronic renal 
failure; endocrine pododermatitis rare.
• Higher incidence in cats than in dogs. 
• Dogs—squamous cell carcinoma; 
epitheliotropic lymphoma, melanoma; mast 
cell tumor; keratoacanthoma; inverted 
papilloma; eccrine adenocarcinoma. 
• Cats—papilloma; squamous cell carcinoma; 
trichoepithelioma; fibrosarcoma; malignant 
fibrous histiocytoma; metastatic primary 
adenocarcinoma or squamous cell carcinoma 
of the lung (feline lung-digit syndrome).
• Dogs—irritant contact dermatitis; trauma; 
concrete and gravel dog runs; excessive 
exercise; clipper burn; foreign bodies; 
thallium toxicity. • Cats—irritant contact 
dermatitis; foreign bodies; thallium toxicity.
• Dogs—sterile interdigital granuloma; 
interdigital follicular cyst (see Physical 
Examination Findings). • Cats—see Physical 
Examination Findings.
• Lifestyle and general husbandry conditions—
influence development. • Excess exercise, 
abrasive or moist housing, poor grooming, 
and/or lack of preventive medical care may 
predispose an animal or exacerbate condition. 
• Body size, foot conformation, and breed 
influence the development of interdigital 
  DIAGNOSIS
See Signs and Causes.CBC/BIOCHEMISTRY/URINALYSIS
IMAGING
• Skin scrapings or hair plucks—demodicosis. 
• Fungal culture—dermatophytosis. 
• Exudate or pustule smear—bacterial or 
yeast infection. • Culture and sensitivity from 
exudates and/or biopsy tissues. • Dogs—
biopsies indicated if skin scrapings are 
negative and lesions (nodules, draining tracts) 
are seen; samples from the ventral surface 
with draining tracts may reveal follicular cysts 
and pyogranulomatous inflammation leading 
to the dorsal surface. • Cats—biopsies may 
be indicated in all cases; pedal dermatosis is 
relatively rare. • Restricted-ingredient food 
trial—food hypersensitivity. • Intradermal 
testing—atopy. • Endocrine assays—
hypothyroidism, hyperadrenocorticism, 
diabetes mellitus.
  TREATMENT
Outpatient, unless surgery is indicated.
Foot soaking and/or bandaging may be 
necessary, depending on cause.
• Depends on underlying cause and severity 
of condition. • Discuss husbandry and 
preventive medical practices. • Many 
etiologies can be managed but not cured.
• Melanoma and squamous cell carcinoma—
very poor prognosis; early diagnosis 
necessitates amputation of the digit(s) or paw. 
• Infectious—may benefit from surgical 
debridement of devitalized tissue before 
medical therapy. • Recurrent draining tracts 
caused by interdigital follicular cysts may be 
cleared with laser ablation.
• Depend on the underlying cause and 
secondary infections; see related chapters for dosages of appropriate medications. 
• Antibiotics based on culture and sensitivity; 
4–6 weeks minimum.
Depend on the treatment protocol selected 
for the underlying cause; see specific drugs 
and their precautions.
Depends on the underlying cause and 
treatment protocol selected.
  FOLLOW-UP
Environmental cause—good husbandry and 
preventive medical care.
• Success of therapy depends on finding the 
underlying cause; often the cause is unknown; 
even when the cause is known, management 
can be frustrating owing to relapses or lack of 
affordable therapeutics. • Often the disease 
can only be managed and not cured. 
• Referral to dermatologist often appropriate. 
• Surgical intervention is sometimes 
Depends on the underlying cause; 
uncommon.
Depends on treatment protocol selected.
Duclos DD. Canine pododermatitis. Vet Clin 
North Am Small Anim Pract 2013, 
43(1):57–87.
Resnick 
available online(continued)  Pododermatitis

1098  Blackwell’s Five-Minute Veterinary Consult  
PPoisoning (Intoxication) Therapy
  BASICS
• Acutely ill patients are often diagnosed as 
poisoned when no other diagnosis is 
obvious.
• Direct initial efforts toward stabilizing the 
patient.
• Proper patient and toxicant assessment are 
critical in determining the appropriate 
decontamination and therapy needs for 
patient.
• Goals of treatment—provide emergency 
intervention; prevent further exposure; 
prevent additional absorption; apply specific 
antidotes; hasten elimination; provide 
supportive measures.
• Valuable time can be saved by applying the 
appropriate treatment for a suspected or 
known intoxicant.
• Suspected intentional intoxication—
suspected toxic materials and specimens 
may be valuable from a medical–legal 
aspect; maintain a proper chain of physical 
evidence and keep excellent medical records if 
malicious intent is suspected.
• Initial patient evaluation includes the 
following:
◦ Assess patient status and review 
signalment.
◦ Determine any current or past medical 
conditions and current medications.
◦ Determine the toxicant patient was 
exposed to as well as the route, dose, and 
time since exposure.
◦ Determining location of exposure may be 
helpful at ruling in or out additional 
potential concerns.
  DIAGNOSIS
• Definitive diagnosis is often difficult; 
animals may come in contact with 
varying substances that pet owners are 
unaware of.
• Pet Poison Helpline, ASPCA Animal 
Poison Control Center, local poison 
control centers, and state diagnostic 
laboratories all offer support in determining 
toxicity risk and potential therapy needs 
for animal.
• When suspected exposure and clinical 
signs do not correlate—offer symptomatic 
and supportive care to treat current signs.
• Confirmation of diagnosis—most 
commonly achieved by finding remnants of 
exposed substance and animal’s clinical status; 
chemical analysis (rarely done and is often 
after the fact).  TREATMENT
Supportive Care
• Control body temperature.
• Maintain respiratory and cardiovascular 
function.
• Control acid–base balance.
• Control CNS disorders—see specific chapters.
• Alleviate pain.
Emergency
• Establish a patent airway.
• Assisted ventilation, as needed.
• Cardiopulmonary resuscitation methods, as 
needed.
• After stabilization—proceed with more 
specific therapeutic measures.
Prevent Absorption
• Remove patient from the affected 
environment, especially with inhaled toxins.
• Protect caregivers as well from inhaled 
toxins.
• Decontamination methods include dermal, 
ocular, respiratory, and gastrointestinal.
Dermal Decontamination: Bathing Skin/
Haircoat
• Indicated for external toxicants.
• Bathe to remove the noxious agent using 
liquid dishwashing detergent.
• Caution : Use protective measures to avoid 
contamination of those handling the patient.
Ocular Decontamination
• Irritants—rinse eye(s) with eye wash or tap 
water for 10–15 minutes. Monitor for signs 
of irritation.
• Corrosives—rinse eye(s) with eye wash or 
tap water for 15–20 minutes and perform 
fluorescein stain; treat as needed.
Respiratory Decontamination
• Removal from source is often sufficient.
• Oxygen and humidified oxygen therapy 
may be necessary in more affected patients.
Gastrointestinal Decontamination
• Emetics:
◦ Of little value beyond 1–2 hours after 
ingestion of many toxicants. Exceptions 
include large ingestions, grapes/raisins, 
gum, chocolate, and plant material.
◦ Do not induce in patients who have 
neurologic abnormalities including severe 
agitation or severe depression/sedation. 
Avoid emesis after ingestion of strong acids, 
alkalis, petroleum distillates or substances 
that may result in a rapid onset of 
◦ Apomorphine—most effective and 
reliable for use in dogs; dopaminergic 
agonist; 0.03–0.04 mg/kg IV or IM, 
crushed tablet for conjunctival administration; emesis occurs within 10 
minutes.
◦ 3% Hydrogen peroxide—emetic of 
choice for home use; 1–2 mL/kg PO, do 
not exceed 45 mL in most dogs, 60 mL in 
large dogs; ineffective and contraindicated 
in cats, not always effective in dogs.
◦ Dexmedetomidine—most effective and 
reliable for use in cats; α2 agonist; 5–10 μg/
kg IM; emesis expected within 10–20 
minutes; reverse with atipamezole (equal 
volume in mL).
◦ Xylazine— α2 agonist for use in cats 
0.44–1 mg/kg IM or SQ. Can be reversed 
with an α2-adrenergic antagonist such as 
atipamezole or yohimbine.
◦ Hydromorphone- mu opioid agonist for 
use in cats; 0.1 mg/kg SQ; emesis expected 
within 5–15 minutes; reverse with naloxone 
(0.01–0.04 mg/kg Im or SQ).
◦ Ipecac—not recommended.
◦ Salt or salt solution—not recommended; 
may result in salt toxicity.
◦ Adsorbant—prevents absorption of toxic 
substance for certain toxicants.
◦ Highly adsorptive of many toxicants 
including rodenticides, insecticides, and 
most over-the-counter and prescription 
◦ Ineffective against xylitol, alcohols, 
chlorate, cyanide, heavy metals, corrosive 
and caustic chemicals, and petroleum 
distillates.
◦ Administered after emetic—increases 
efficacy of toxicant elimination.
◦ Dosage 1–5 g/kg body weight; generally 
a single dose administration; multidose 
administration if substance undergoes 
enterohepatic circulation (1–2 g/kg PO 
q6-8h for 24 hours).
◦ Generally administered with a cathartic 
such as sorbitol; only the first dose should 
contain a cathartic. Magnesium-containing 
cathartics should be avoided or used with 
caution.
◦ Hypernatremia has been reported after 
administration of activated charcoal, 
especially when a cathartic (sorbitol) is used 
in a dehydrated patient. Sub q or IV fluids 
can help to minimize risk.
• Gastric lavage:
◦ Indicated in patients who are not 
acceptable candidates for emesis, have 
ingested a potentially life-threatening toxin 
or if emesis was unsuccessful. Most effective 
if performed in the first 1–2 hours.
◦ An appropriately sized cuffed endotracheal 
tube must be in place prior to starting the 
lavage procedure.
◦ Orogastric (stomach) tube size—use the 
largest possible; a good rule: use the same 
size as the cuffed endotracheal tube 
(1 mm = 3 Fr), measured to the last rib.

Canine and Feline, Seventh Edition  1099
P
◦ Volume of warm water or lavage solution 
for each washing—5–10 mL/kg body 
weight; avoid forceful administration.
◦ Agitate stomach and either aspirate or 
allow gravity drainage of stomach contents. 
Activated charcoal with a cathartic can be 
infused, if indicated, before removing 
orogastric tube; however, caution should be 
used to ensure patient maintains a protected 
airway in the event of regurgitation.
◦ Procedure should only be used in 
appropriate exposures and proper patient 
status.
• Surgery or endoscopic removal:
◦ May be indicated for coins, metals, 
batteries, and drug-infused patches.
• Enemas:
◦ May hasten the elimination of toxicants 
from the lower gastrointestinal tract.
◦ Warm water ± lubricant.
◦ Take care to avoid the induction of 
dehydration and electrolyte imbalances 
with overzealous treatment.
Enhance Elimination
• Absorbed toxicants—often excreted by the 
kidneys; may be excreted by other routes (e.g., 
bile, feces, lungs, and other body secretions).
• Renal excretion—may be manipulated in 
many animals.
• Urinary excretion—may be enhanced using 
diuretics or by altering the pH of the urine; 
not frequently performed.
Diuretics
• Enhance urinary excretion of some 
toxicants—requires maintenance of adequate 
• If minimum urine flow cannot be 
established—must use peritoneal dialysis 
(normal urine output is 1–2 mL/kg/h).
• Agents of choice—furosemide 2 mg/kg IV 
q6–8h, if no response increase dose to 4–6 
mg/kg IV q6–8h, or mannitol 1–2 g/kg IV 
slowly over 20–30 minutes q6h.
• Caution should be used as electrolyte 
abnormalities may occur.Manipulating Urine pH
• Not routinely performed; elimination may 
not be enhanced to a level that improves 
clinical outcome and may cause or worsen 
• Acidic compounds remain ionized in 
alkaline urine; alkaline compounds remain 
ionized in acidic urine.
• IV 0.9% sodium chloride—rapid, urinary 
acidifying agent.
• IV sodium bicarbonate may be used as an 
alkalinizing agent.
• Consider volume replacement with 
crystalloids and colloids if necessary.
• May enhance elimination of toxicants that 
undergo renal excretion.
Peritoneal Dialysis
• Potentially indicated for water-soluble, 
low-molecular-weight, poorly protein-bound 
compounds with a small volume of distrib -
ution such as alcohols, lithium, and 
salicylates.
• Indicated for simple removal of absorbed 
toxicants in patient with normal renal 
function.
• pH of the solution—may be altered to 
maintain the ionized state of the offending 
compound.
Lipid Emulsion Therapy
• Promising use as antidote for toxicosis from 
many fat-soluble drugs.
• Has been used successfully in veterinary 
medicine to treat toxicity from highly 
lipophilic drugs such as baclofen, beta 
antagonists, calcium channel antagonists, 
ivermectin, moxidectin, and other fat-soluble 
• Exact mechanism of action remains 
unknown, but may act as a lipid sink.
• Potential adverse effects, although rare, 
include hyperlipidemia, hepatosplenomegaly, 
jaundice, seizures, hemolytic anemia, 
prolonged clotting time, thrombocytopenia, 
and fat embolism.• Dosage extrapolated from humans using 
the 20% commercially available fat emulsion 
product. Standard protocol: 1.5–4 mL/kg IV 
over 5–10 minutes followed by 0.25 mL/kg/
min CRI over 30–60 minutes. Repeat approx  - 
imately every 6 hours, as needed, for up to 
3–5 doses. If serum lipemia is present, wait 
1–2 hours before readministration. See 
Appendix V on Antidotes and Useful Drugs.
Specific antidotes or procedures are available 
for the more common toxicants; see specific 
chapters and Appendix V.
  FOLLOW-UP
Specific monitoring depends on the toxicant 
and the patient’s signs and laboratory 
• Pet Poison Helpline: http://www.
petpoisonhelpline.com/
• ASPCA Poison Control Center: http://
www.aspca.org/pet-care/poison-control/
Toxicology, 3rd ed. Philadelphia, PA: 
Saunders, 2013.
Author  Renee D. Schmid
acknowledge the prior contribution of Tam 
Garland and E. Murl Bailey.(continued)  Poisoning (Intoxication) Therapy

1100  Blackwell’s Five-Minute Veterinary Consult  
PPolioencephalomyelitis—Cats
  BASICS
OVERVIEW
• Subacute to chronic nonsuppurative 
encephalomyelitis with a predominance of 
pathologic changes in the gray matter, mainly 
affecting the medulla oblongata and the 
• This disease is considered rare, with a 
prevalence of less than 1% in cats presented 
with spinal cord diseases.
• There is no breed or sex predilection.
• Cats of any age can be affected.
• The disease is sporadic but has been 
observed worldwide, especially in northern 
Europe.
SIGNS
• Ataxia, paresis, and decreased postural 
reactions of pelvic or all four limbs.
• Lower motor neuron signs may be also 
possible (muscle atrophy and decreased to 
absent segmental spinal reflexes).
• Intracranial signs (seizures, cerebellar signs, 
and cranial nerve deficits) are uncommon.
• The progression is subacute to chronic 
(over weeks to months) but may also stabilize.
The underlying cause remains still unknown 
but pathologic findings are highly suggestive 
of a viral agent.
  DIAGNOSIS
• Fungal infection.
• Laboratory changes not well characterized.
• Nonspecific changes (e.g., leukopenia and 
non-regenerative anemia) rare.OTHER LABORATORY TESTS
N/A
• The presumptive diagnosis is based on 
history, clinical signs, and possibly CSF 
changes (mononuclear pleocytosis with or 
without moderate increased total protein 
levels).
• The final diagnosis is based on histopathol-
ogy (disseminated inflammatory lesions in the 
brain and spinal cord and, as the disease 
progresses, there is extensive neuronal loss 
and astrogliosis with little inflammation).
  TREATMENT
No curative treatment has been found.
• No drug therapy used in reported cases.
• Because lesions are nonsuppurative, steroid 
therapy may palliate clinical signs, at least 
temporarily.
• Supportive treatment with antiepileptic 
medication to control seizures if indicated.
  FOLLOW-UP
Prognosis can be good if the neurologic signs 
are mild and nonprogressive.
Gunn-Moore D. Infectious diseases of the 
central nervous system. Vet Clin North Am 
Small Anim Pract 2005, 35:103–128.
Hoff EJ, Vandevelde M. Non-suppurative 
encephalomyelitis in cats suggestive of a 
viral origin. Vet Pathol 1981, 18:170–180.Tipold A. Inflammatory diseases of the spine 
Anim Pract 2010, 40:871–879.
Tipold A, Vandevelde M. Neurological 
diseases of suspected infectious origin and 
prion disease. In: Greene CE, eds., 
ed. St. Louis, MO: Elsevier, 2012, p. 860.

Canine and Feline, Seventh Edition  1101
PPolyarthritis, Erosive, Immune-Mediated
  BASICS
• An autoimmune disease of the joint that 
results in destruction of articular cartilage, 
subchondral bone and surrounding ligaments. 
This damage can result in joint instability, 
laxity and deformation with chronicity. 
• Canine syndromes: ◦ Rheumatoid 
arthritis—antibody response against 
rheumatoid factors or autoantibodies that 
results in severe damage to the articular 
cartilage, periarticular bone and ligaments. 
◦ Felty’s syndrome—constellation of arthritis, 
neutropenia, and splenomegaly. ◦ Erosive 
polyarthritis of greyhounds—minimal 
subchondral changes despite necrosis of the 
articular cartilage and proliferative synovitis; 
peripheral lymphadenopathy. • Feline erosive 
polyarthritis: ◦ Periosteal proliferative 
polyarthritis—acute onset of pain and 
systemic manifestations (fever, lymphadeno­
pathy) related to arthropathy with prolific 
periarticular periosteal bone formation. 
◦ Feline rheumatoid arthritis—insidious 
development of joint deformity accompanied 
by less systemic illness and periosteal bone 
• Immune ­complex deposition within the 
synovial membrane results in an inflamm­
atory response (involving complement and 
cytokines) leading to cartilage erosion. 
Release of matrix ­degrading enzymes 
(metalloproteases) responsible for cartilage 
destruction. • Chronic synovitis results in a 
pannus, or granulation tissue, across the 
articular cartilage that extends into 
subchondral bone, replacing areas of 
destruction. • Destruction of joint ligaments 
leads to joint instability and luxation.
GENETICS
No genetic predisposition known.
• Uncommon to rare. • Nonerosive disease 
Species
• More common in small ­breed dogs; 
Shetland sheepdogs, cocker spaniels, collies 
appear more affected. • Siamese cats.
• Canine—middle age (3–9.5 years). 
• Feline—bimodal distribution of young 
adults and middle ­aged to older cats.Predominant Sex
• Feline—predominantly male. • Dogs—none.
SIGNS
• Typically affects more distal joints (carpus, 
elbow, stifle and tarsal joints more 
frequently, digital joints and vertebral 
column may be affected). • Clinically, it can 
appear as though only one joint is affected. 
• Evaluate cats for causes of reactive 
polyarthritis (septic arthritis, systemic 
infection and neoplasia).
• Progressive, intermittent, or shifting ­leg 
lameness. • Reluctance to walk or stand, 
inappetence and weight loss.
• Pain and/or effusion detected on palpation 
of one or more joints. • Deformation, 
instability, and luxation of the joint is unique 
to erosive (as compared to nonerosive) 
arthritis; occurs with chronicity. May be 
associated with cranial cruciate ligament 
rupture (CCLR). • Stiffness on gait 
evaluation, decreased range of motion and 
muscle atrophy. • Pyrexia and/or peripheral 
lymphadenopathy. • Cats may resent 
handling. May present with acute signs or 
may be more insidious over weeks to months.
CAUSES
• Underlying etiology has yet to be identified. 
• Canine distemper virus within synovial 
fluid can result in sustained inflammation 
within the joint possibly predisposing a dog 
to erosive arthritis. • Feline leukemia virus 
(FeLV) and feline syncytium ­forming virus 
are associated with feline periosteal prolif­
erative polyarthritis (FPPP), but causation has 
not been shown.
None currently known.
  DIAGNOSIS
• Other causes of arthropathy—infectious 
arthritis, degenerative joint disease, neoplasia 
(e.g., synovial cell sarcoma), hemarthrosis, 
congenital arthropathies (elbow dysplasia, 
osteochondrosis dissecans), tick ­borne 
disease. • Hypertrophic osteodystrophy. 
• Panosteitis. • Polymyositis. • Steroid ­
responsive meningitis–arteritis. • Systemic 
lupus erythematosus (SLE). • Reactive 
polyarthritis due to antigenic stimulation 
from systemic disease. • Drug ­induced 
polyarthritis (sulfa drugs, phenobarbital, 
erythropoietin, penicillins, cephalosporins, 
vaccines). • T rauma.CBC/BIOCHEMISTRY/URINALYSIS
• Hemogram—a mild, non ­regenerative 
anemia and mild leukocytosis may be present 
although hemogram can be unremarkable. 
• Chemistry—hyperglobulinemia may be 
present. • Urinalysis and urine culture—
generally unremarkable. Proteinuria should 
be quantified with a UPC.
• Synovial fluid analysis—aseptic, neutro­
philic, or mixed inflammation with greater 
than 10% non ­degenerate neutro  phils: 
◦ Protein concentration often >3.0 g/dL and 
total nucleated cell count (TNCC) usually 
>3,000 cells/ μL (not associated with severity). 
◦ Make a direct smear prior to lab 
submission. • Synovial fluid culture (bacteria 
and mycoplasma)—negative results do not 
entirely rule out septic arthritis. • Antinuclear 
antibody titers—usually negative, unlikely to 
be clinically useful unless SLE suspected. 
• Rheumatoid factor testing—positive test is 
supportive only when erosive disease is 
present; other causes of joint disease can 
elevate rheumatoid factor levels: ◦ Positive 
results seen in cats with rheumatoid arthritis, 
not in FPPP . • Testing for infectious diseases 
(tick­borne disease ( Borrelia , Ehrlichia , 
Rickettsia ), FeLV/feline immunodeficiency 
virus (FIV) testing, systemic mycoses, 
Leishmania  if endemic, blood and urine 
culture, ± echocardiogram for bacterial 
endocarditis). • CSF collection, serum 
creatine kinase, and direct Coombs’ testing 
can be considered on an individual basis to 
evaluate for systemic diseases.
IMAGING
• Joints: ◦ Imaging of multiple joints is 
recommended; initial radiographs may be 
unremarkable without obvious change for 6 
or more months. ◦ Progressive disease results 
in subchondral bone lysis, irregular joint 
surface, and narrowing or widening of the 
joint space, calcification of soft tissues around 
the joint, and extensive bone destruction. 
◦ Cats can have periosteal new bone formation 
and enthesophytes. • Thoracic and vertebral 
radiographs with abdominal ultrasound can 
help rule out reactive polyarthritis.
Arthrocentesis (joint tap): four joints should 
be sampled.
• Grossly, the synovium can be discolored, 
thickened, and ulcerated with extension of 
granulation tissue into the subchondral bone. 
• Histopathology of synovial membrane is 
rarely necessary, but may reveal synovial 
hypertrophy and hyperplasia, necrosis, and 
mononuclear inflammation (often lympho ­ 
plasmacytic).

1102  Blackwell’s Five-Minute Veterinary Consult  
P  TREATMENT
Larger dogs may require more assistance and 
support during treatment.
ACTIVITY
Strict rest is recommended while 
symptomatic and painful.
DIET
No dietary restrictions.
• Management is lifelong. • Erosive disease is 
often progressive and less responsive to 
treatment. • Importance of weight 
• Arthrodesis (primarily carpal) has been used 
for joint luxation to improve quality of life. 
• Surgical repair of CCLR if necessary. 
• Synovectomy, arthroplasty, or joint 
replacement can be considered. 
• Splenectomy as last resort in Felty’s 
syndrome.
• Doxycycline or minocycline recommended 
in cats and dogs while infectious disease 
testing is pending. • Tylosin trial in 
greyhounds for mycoplasma.
Dogs
Initial Therapy
• Prednisone or prednisolone 1–2 mg/kg/day 
or 50 mg/m2, until remission encountered 
(often 4 weeks), then taper. • Cyclosporine 5 
mg/kg PO q12—suitable alternative to 
Combination Therapy
Can be helpful to achieve remission, allow for 
tapering of corticosteroids and aid in 
refractory cases; each can be combined with 
corticosteroids:
• Mycophenolate mofetil 10 mg/kg PO 
q12h; taper by 50% after 2–3 weeks or if 
hemorrhagic gastrointestinal signs noted. 
• Leflunomide 3–4 mg/kg PO q24h; allow 4–6 weeks before decreasing dose to every 48 
hours then every 72 hours. • Azathioprine 
1.6–2 mg/kg PO q24h for 2 weeks or until 
remission, then taper to every 48 hours. 
• Other immunosuppressives to consider 
include chlorambucil, cyclophosphamide, 
levamisole, methotrexate.
Cats
• Prednisolone 2 mg/kg PO q12h followed by a 
taper; ~50% of cats with FPPP show 
improvement in signs and slowing of 
progression when used with analgesia. • 58% of 
cats improved using a protocol of methotrexate 
+ leflunomide: methotrexate 2.5 mg/cat PO 
q12h for 3 consecutive doses (7.5 mg/24 hours) 
repeated weekly until improvement then 2.5 
mg/cat PO weekly; leflunomide 10 mg/cat PO 
q24h until improvement then 10 mg/cat PO 
twice weekly. • Other immunosuppressive 
agents that can be considered include 
cyclosporine or chlorambucil.
Other
Omega ­3 fatty acid supplementation.
Analgesia
Gabapentin 5–15 mg/kg PO q8–12h; 
amantadine 3–5 mg/kg PO q24h; 
nonsteroidal anti ­inflammatory drug 
(NSAIDs) as appropriate if not using 
Glucocorticoids should not be given with 
NSAIDs.
• Tapering immunosuppressive therapy too 
soon can lead to relapses. • Confirm aseptic 
inflammation prior to initiating immuno­
suppressive therapy. • Consider secondary 
immunosuppressive agent if unable to attain 
remission or if symptoms relapse while still 
on glucocorticoids. • Monitor for infectious 
diseases and opportunistic infections.
Concurrent use of multiple immuno­
suppressives with the same mechanism of 
action.
  FOLLOW-UP
• Monitor for potential side effects of 
treatments (liver enzymes, hyperglycemia, 
etc.) and concurrent disorders (e.g., 
hematologic abnormalities, proteinuria, etc.) as necessary, • Tapering of medications often 
possible after 4 weeks of therapy. A 50% taper 
every month or dose reduction of 25–30% 
every 2–3 weeks with a minimum of 4 
months of therapy can be considered. • If 
relapse occurs during taper, increase 
corticosteroid to the most recent effective 
dose and/or consider a second agent, if not 
already utilized. • If relapse occurs after the 
taper, a short course of corticosteroid and the 
dose of the second agent that maintained 
clinical control can be utilized long term. 
• Serial or repeated arthrocentesis can be 
performed to rule out poor control of immune ­ 
mediated disease in cases of ongoing or 
recurrent lameness. In some dogs, this may 
identify degenerative joint disease as the cause 
of lameness rather than relapse of 
• Erosive disease is typically progressive; 
~50% of cats will improve with good quality 
of life. • Monitoring recommended if initially 
nonerosive. • Tick­borne disease usually 
responds to appropriate antibiotic therapy 
within 7 days.
• CCLR = cranial cruciate ligament rupture.
• FPPP = feline periosteal proliferative 
• TNCC = total nucleated cell count.
Lemetayer J, Taylor S. Inflammatory joint 
disease in cats: diagnostic approach and 
treatment. J Feline Med Surg 2014, 
16(7):547–562.
Shaughnessy M, Sample S, Abicht C, et al. 
Clinical features and pathological joint 
changes in dogs with erosive immune ­
mediated polyarthritis: 13 cases (2004–
2012). J Am Vet Med Assoc 2016, 
249(10):1156–1164.
Consulting Editor  Mathieu M. Glassman 
available onlinePolyarthritis, Erosive, Immune-Mediated  (continued)

Canine and Feline, Seventh Edition  1103
PPolyarthritis, Nonerosive, Immune-Mediated, Dogs
  BASICS
• Nonerosive polyarthritis—a non-infectious 
inflammatory disease of multiple (>2) joints 
without radiographic evidence of bone or 
cartilage involvement. • Most common 
polyarthropathy in dogs, idiopathic or type I 
immune-mediated polyarthritis (IMPA). 
• Reactive polyarthropathy, where 
inflammation in the joints is secondary to 
distant disease, includes types II, III, and 
IV—disease is secondary to chronic 
inflammatory or infectious disease, chronic 
gastrointestinal disease, and neoplasia, 
respectively. • Systemic lupus erythematosus 
(SLE), familial shar-pei fever (FSF), and 
familial juvenile-onset polyarthritis of Akitas 
are less common nonerosive polyarthritides.
• All causes of nonerosive polyarthritis are 
immune-mediated. • Immune complex 
deposition is the underlying mechanism in 
idiopathic IMPA (type I) and reactive poly -
arthropathy (types II, III, and IV). • Reactive 
polyarthropathy involves immune stimulus 
distant to the joints due to underlying 
infectious, inflammatory, or neoplastic disease, 
as well as adverse drug reactions, with 
subsequent immune complex deposition in the 
synovium. • SLE is the result of immune 
complex deposition secondary to autoantibodies 
(antinuclear antibodies [ANA]) formed against 
tissue proteins and DNA. • FSF is the result of 
amyloid deposition in the synovium.
• Musculoskeletal: ◦ Appendicular joints are 
more commonly affected than axial joints. 
Intervertebral joints are not usually affected. 
◦ Distal joints (carpus, tarsus) are more 
commonly affected than proximal joints (stifle, 
shoulder, coxofemoral) in IMPA. ◦ The hock 
joints are typically affected in FSF . • Hemic/
lymphatic/immune: ◦ Immune stimulus may 
result in fever, lethargy, and poor appetite. 
◦ Hemolytic anemia and thrombocytopenia 
may be present in SLE. • Skin/exocrine: 
◦ Immune-mediated skin disease targeting the 
mucocutaneous junctions is common in SLE. 
• Renal/urologic: ◦ Immune-complex 
deposition in the kidneys and protein-losing 
nephropathy may be present in SLE. 
◦ Glomerulonephropathy and proteinuria 
secondary to amyloidosis may occur in FSF .
GENETICS
MTBP  gene missense mutation is believed to 
be responsible for FSF .
• Idiopathic IMPA is common in dogs. 
• Reactive polyarthritis accounts for only 
25% of nonerosive polyarthritis cases in dogs. 
• IMPA is rare in cats.SIGNALMENT
Species
• Large-breed dogs, such as Labrador 
retrievers, golden retrievers, Rottweilers, Irish 
setters, Shetland sheepdogs, cocker spaniels, 
and American Eskimo dogs are over -
represented for idiopathic IMPA. 
• Doberman pinschers are overreported in 
cases of polyarthropathy secondary to 
sulfonamide administration.
Mean age 4–6 years old, range 6 months to 
12 years.
SIGNS
• Shifting limb lameness. • Stiff gait. • Fever. 
• Reluctance to walk. • Lethargy. 
• Inappetence. • Exercise intolerance. 
• Joint pain. • Joint effusion. • Fever. 
CAUSES
• Type I IMPA—idiopathic. • Immune-
mediated dermatopathy and hepatopathy are 
among the most common noninfectious 
causes of type II IMPA. Infectious sources to 
consider include endocarditis, discospondylitis, 
prostatitis, deep pyoderma, and systemic 
infections (fungal, protozoal). • Type III 
IMPA occurs secondary to chronic gastro -
intestinal disease such as inflammatory bowel 
disease, but is rare. • Type IV IMPA has been 
reported secondary to renal carcinoma, 
mammary carcinoma, leiomyoma, Sertoli cell 
tumor, and seminoma. • Drugs implicated in 
adverse drug reaction-related polyarthropathy 
(type II) include human albumin, erythro-
poeitin, phenobarbital, and antibiotics such 
as sulfonamides, cephalosporins, penicillins, 
lincosamides, and macrolides. This should be 
considered a potential cause when adminis-
tered 5–20 days prior to the onset of signs. 
• Reports of postvaccinal polyarthropathy 
have included canine distemper and Lyme 
vaccines, typically within 30 days of vaccine 
N/A
  DIAGNOSIS
• Infectious polyarthritis, including rickettsial 
disease, Mycoplasma , bacterial, and fungal 
etiologies: ◦ Borrelia burgdorferi , Anaplasma phagocytophilum , Rickettsia rickettsii , Ehrlichia 
canis, E. ewingii , and E. chaffeensis  are among 
the rickettsial diseases that should be considered 
for polyarthropathy. • Leishmaniasis should be 
considered, particularly in instances of 
significant systemic involvement, presence of 
skin lesions, and/or history of travel to the 
Mediterranean/southern Europe, Africa, India, 
or South America within the past 7 years. 
• Panosteitis and hypertrophic osteodystrophy 
should be considered, particularly in young 
dogs with lameness and fever. • Degenerative 
joint disease (DJD) should be considered in 
middle-age to older animals. • Viral etiologies 
have been implicated as a cause of polyarthritis 
in cats, including feline calicivirus and feline 
coronavirus associated with feline infectious 
• CBC—mild non-regenerative anemia and 
mild leukocytosis; leukopenia is also possible. 
Presence of thrombocytopenia may be 
suggestive of tick-borne disease or when 
severe, SLE. • Chemistry—often normal, 
except when distant (reactive polyarthropathy) 
or polysystemic disease (SLE) is present. 
• Urinalysis—proteinuria may be present and 
should prompt obtaining a UPC.
• Definitive diagnosis can be obtained by 
arthrocentesis and cytology of multiple joints. 
• Aerobic and anerobic joint culture to 
definitively exclude septic arthritis in all cases; 
sensitivity is ~50% and can be improved with 
broth-enrichment media and incubation prior 
to culture. • Fungal cultures of joint fluid may 
be considered, though direct joint involvement 
is rare. • Mycoplasmal PCR or culture of 
synovial fluid may be considered, with PCR 
being more sensitive. • Tick PCR panels to 
exclude rickettsial disease should be performed 
in all cases. Quantitative serology may be 
considered but positive results may lag behind 
onset of clinical signs, and false-negative 
results are common. Qualitative tests for 
antibody production, including SNAP ELISA 
tests, may be indicated in cases with high 
index of clinical suspicion for rickettsial 
diseases such as Lyme disease. • Serologic 
fungal titers may be considered where fungal 
disease is endemic or there has been travel 
history to rule it out as a cause of reactive 
polyarthropathy. • Blood and urine cultures 
should be considered to exclude bacterial 
causes of reactive polyarthropathy in cases 
where no obvious infectious or inflammatory 
focus is identified. Positive blood cultures may 
be indicative of primary septic polyarthritis of 
hematogenous origin given relatively low 
sensitivity of bacterial culture of synovial fluid. 
• C-reactive protein (CRP) can be measured 
as a nonspecific indicator of inflammation and 
reassessed for response to therapy. • ANA titer 
may be submitted in cases where there is 
multisystemic immune-mediated involvement.

1104  Blackwell’s Five-Minute Veterinary Consult  
PIMAGING
• Appendicular radiographs including 
affected joints are necessary to exclude erosive 
causes of polyarthropathy, though these 
diseases are uncommon in dogs and may not 
be radiographically visible initially. Absence of 
palpable joint effusion should not preclude 
recommendation to obtain radiographs in 
cases where clinical suspicion is otherwise 
suggestive of polyarthritis and screening 
radiographs of multiple joints should be 
obtained. • Joint effusion is the main radio -
graphic finding. Radiographic signs of 
osteoarthritis may be concurrently present 
and do not exclude nonerosive polyarthritis as 
a diagnosis. • Thoracic radiography, 
abdominal ultrasonography, and echocardio -
graphy should ideally be performed to assess 
for causes of reactive polyarthropathy.
• Arthrocentesis should be performed 
aseptically on 3–5 joints for synovial fluid 
collection, under sedation or general 
anesthesia. • Synovial biopsy can be used for 
confirmation in challenging cases.
• T urbid ± reduced viscosity of synovial fluid, 
± voluminous fluid. • Synovial fluid cytology 
characterized by predominantly neutrophilic 
(>10%) inflammation without evidence of 
infectious agents in the synovial fluid.
  TREATMENT
• Typically outpatient therapy.
• Systemic signs (i.e., fever, inappetence) may 
necessitate hospitalized supportive care.
ACTIVITY
Activity restriction to avoid exacerbation of 
pain and lameness.
DIET
Weight reduction as applicable to avoid 
undue stress on joints.
Discuss failure to control clinical signs, 
particularly in cases where underlying disease 
cannot be eliminated, and possibility or 
recurrence and/or need for lifelong 
medication and monitoring.
• Immunosuppressive dose of steroids, i.e., 
prednisone (dog) or prednisolone (cat):  2 mg/kg/day PO for 4 weeks, then gradually 
tapered over at least 4 months unless 
combination immunosuppressive protocols 
are used. • Nonsteroidal anti-inflammatory 
drugs (NSAIDs) for FSF , i.e., carprofen 2.2 
mg/kg PO twice daily.
Consider risks and complications of 
prolonged steroid courses, including 
immunosuppression, diabetes mellitus, risk 
for congestive heart failure, and 
muscle-wasting.
NSAIDs and steroids should be not be given 
together due to increased risk of gastro -
intestinal ulceration; a 7-day washout period 
is indicated between medications.
• Cyclosporine—dog: 5 mg/kg PO twice 
daily; cat: 4 mg/kg PO twice daily. 
• Mycophenolate mofetil—dog: 10 mg/kg 
PO or IV twice daily. • Leflunomide—dog: 
2–4 mg/kg PO once daily; cat: 10 mg/cat PO 
once daily. • Azathioprine—dog: 2 mg/kg 
PO once daily, tapered to 0.5–2 mg/kg PO 
every other day. • Chlorambucil—dog: 1–2 
mg/m2 PO once daily; cat: 15 mg/m2 PO 
once daily for 4 days once every 3 weeks or 
2 mg/cat every other day. • Cyclophosphamide—  
dog: 1.5 mg/kg PO when patient >25 kg, 2 
mg/kg PO when patient 5–25 kg, 2.5 mg/kg 
PO when patient <5 kg every other day or 4 
consecutive days of the week; cat: 2.5 mg/kg 
once daily. • Analgesics may be considered 
for additional pain control (e.g., gabapentin 
(dog), 5–10 mg/kg PO twice daily). • Given 
the disease is rare in cats, consider doxycycline 
5 mg/kg PO twice daily for 14 days to treat 
infectious etiologies prior to initiating 
  FOLLOW-UP
• Repeat arthrocentesis may be considered 
for evaluation of response to treatment, 
especially prior to medication changes (i.e., 
at 4 weeks, prior to beginning steroid taper). 
• CRP has a modest correlation to synovial 
fluid cytology and may be performed as a 
noninvasive means of patient monitoring. 
• CRP and IL-6 may be used to distinguish 
recurrence of IMPA from osteoarthritis.
Avoid nonessential vaccination for prevention 
of recurrence. Canine distemper vaccine 
should not be given if seroprotective antibody 
titer levels are present.POSSIBLE COMPLICATIONS
• Immunosuppression and risk of secondary 
infection, particularly when multiple 
immunosuppressive drugs are used. 
• Subsequent DJD may occur following 
IMPA. Patients may show lameness when 
steroid therapy is tapered, however most are 
afebrile.
• Good prognosis for idiopathic IMPA with 
expected improvement in clinical signs within 
7 days. • Recurrence is possible and reported 
in almost 30% of cases. • 10% of cases fail to 
respond to immunosuppressive therapy. 
• Variable prognosis for reactive polyarthro -
pathy, depending on the ability to eliminate 
or control the underlying disease process. 
• Guarded prognosis for SLE.
• ANA = antinuclear antibody. • CRP = 
C-reactive protein. • DJD = degenerative 
joint disease. • FSF = familial shar-pei fever. 
• IL-6 = interleukin-6. • IMPA = immune-
mediated polyarthritis. • NSAID = 
• SLE = systemic lupus erythematosus.
Clements DN, Gear RNA, Tattersall J, et al. 
Type I immune-mediated polyarthritis in 
dogs: 39 cases (1997–2002). J Am Vet Med 
Assoc 2004, 224:1323–1327.
Hillstrom A, Bylin J, Hagman R, et al. 
Measurement of serum C-reactive protein 
concentration for discriminating between 
suppurative arthritis and osteoarthritis in 
dogs. BMC Vet Res 2016, 12:240–249.
16:547–562.
Stone M. Immune-mediated polyarthritis and 
other polyarthritides. In: Ettinger SJ, ed., 
8th ed. St. Louis, MO: Elsevier, 2017, 
pp. 3055–3070.
Authors  Ashley E. Bava and J.D. Foster
Consulting Editor  Mathieu M. GlassmanPolyarthritis, Nonerosive, Immune-Mediated, Dogs  (continued)

Canine and Feline, Seventh Edition  1105
P
  BASICS
OVERVIEW
Disorder in which large portions of normal 
renal parenchyma are displaced by multiple 
cysts; renal cysts develop in nephrons and 
collecting ducts; both kidneys are invariably 
affected. In most cases the disease is inherited, 
irreversible, and progressive.
• Persian and related breeds (e.g., exotic 
shorthair, Himalayan, British shorthair) more 
• Dog breeds affected include Cairn terriers 
and beagles.
SIGNS
• Cysts are clinically silent until their 
increasing size and number contribute to 
azotemia or abdominal enlargement.
• May detect bosselated (lumpy) kidneys by 
abdominal palpation.
• Most renal cysts are not painful when 
palpated, but acute secondary infection may 
cause rapid distension of the renal capsule 
and pain.
• Autosomal-dominant inheritance in Persian 
cats.
• Cause of renal cyst formation remains 
obscure; genetic, endogenous, and environ -
mental factors appear to influence the 
process.
  DIAGNOSIS
• Other multicystic diseases of the kidneys.
• Glomerulocystic disease of collies.
• Renal cystadenocarcinoma associated with 
nodular fibrosis in German shepherd dogs.
• Renal cysts associated with chronic kidney 
disease (CKD) or renal dysplasia.
• Renal neoplasia.
• Perirenal pseudocysts.
• Mycotic or bacterial nephritis.
• Results unremarkable unless patient has 
CKD.
• Hematuria is rare.
• Genetic tests are available to identify the 
autosomal dominant polycystic kidney disease 
(AD-PKD) type 1 mutation in cats. This test 
is useful to screen kittens less than 3–4 
months old when ultrasonography may be 
less sensitive, as well as in breeding cats. Other mutations may also cause inherited 
kidney cysts.
• Cyst fluid can be clear, cloudy, or 
hemorrhagic, and the fluid from two cysts in 
the same kidney can differ.
• Bacterial culture of cyst fluid aids in 
diagnosing infection.
IMAGING
Survey radiography and IV contrast urography 
are insensitive methods of confirming cystic 
disease.
• Reveals anechoic cavitating lesions 
characterized by sharply marginated smooth 
walls and distal enhancement.
• Can usually detect cysts >2 mm in diameter.
• Cysts have been detected in cats as young as 
7 weeks; screening cats younger than 6 
months is associated with higher false-
negative results.
• Hypoechoic cystic cavities may be seen in 
some cysts infected with bacteria.
• Detection of cysts in other organs which 
helps to differentiate AD-PKD from other 
inherited or acquired multicystic disorders of 
the kidneys.
Evaluation of fine-needle aspirates of the 
kidney may allow differentiation of cystic 
disease from other diseases that cause 
renomegaly.
  TREATMENT
• Usually not life-threatening, but 
pyelonephritis and cyst involvement warrant 
immediate measures to prevent sepsis and 
• Most cysts increase in size and number, 
often impairing adjacent renal parenchyma.
• Elimination of renal cysts is not yet feasible; 
treatment is limited to minimizing the 
consequences of renal cyst formation (i.e., 
CKD, infection, hematuria, and pain).
• Removing fluid from large cysts may 
minimize pain and compression of adjacent 
renal parenchyma. This procedure is 
impractical in kidneys with multiple large cysts.
• A vasopressin antagonist (tolvaptan), has 
been shown to slow kidney enlargement and 
slow decline in kidney function in people 
with AD-PKD.
• Some patients require treatment for 
concomitant CKD.
• Consider nephrectomy only if infected cysts 
are associated with uncontrollable sepsis.
• Disease eradication by selective breeding of 
unaffected cats may be impossible because 
~40% of Persians are affected.  MEDICATIONS
• Bacterial infection of cysts is rare. Unless 
infection is accompanied by pyelonephritis, 
bacteria may not be observed in urine. 
Consider parenchymal infection when cysts 
are associated with renal pain and fever, even 
in absence of bacteriuria.
• The acidic cyst fluid and its epithelial 
barrier may reduce concentrations of acidic 
antibiotics (e.g., cephalosporins and 
penicillins) within cystic lumens. Alkaline, 
lipid-soluble antibiotics (e.g., trimethoprim–
sulfonamide, fluoroquinolones, chloram -
phenicol, tetracycline, and clindamycin), 
which penetrate epithelial barriers and 
become ionized and trapped in cyst lumens, 
are recommended.
  FOLLOW-UP
• Monitor every 2–6 months for progressive 
disease (e.g., CKD, renal infection, and pain).
• In the absence of sepsis, the short-term 
prognosis is favorable.
• AD-PKD = autosomal dominant-polycystic 
Bonazzi M, Volta A, Gnudi G, et al. 
Comparison between ultrasound and 
genetic testing for early diagnosis of 
polycystic kidney disease in Persian and 
Exotic Shorthair cats. J Feline Med Surg 
2009, 11:430–434.
A. Osborne.Polycystic Kidney Disease

1106  Blackwell’s Five-Minute Veterinary Consult  
PPolycythemia Vera
  BASICS
OVERVIEW
Myeloproliferative disorder of the chronic 
myelogenous leukemia (CML) spectrum, 
resulting in high blood viscosity secondary to 
an increased red blood cell (RBC) mass.
• Primarily old animals.
SIGNS
• Gradual in onset; may be incidental 
• Polydipsia and polyuria.
• Erythema of skin and mucous membranes.
• Dilated and tortuous retinal blood vessels.
• Uveitis.
• Splenomegaly and hepatomegaly 
uncommon.
A JAK2  mutation has been implicated in the 
disease pathogenesis.
  DIAGNOSIS
Diagnostic tests should exclude all other 
conditions that may lead to increased packed 
cell volume (PCV) and RBC mass.
• Chronic pyelonephritis.
• Androgen stimulation.
• Chronic pulmonary disease.
• Cardiac disease with right-to-left shunts.
• High PCV.
• Absolute increase in RBC mass.
• Prerenal azotemia possible.
• Leukocytosis in 50% of dogs.
• Pao2—normal.
• Serum erythropoietin concentrations are 
usually low to zero and often overlap with 
those reported for other causes of 
polycythemia.
• Cytologic examination of bone marrow and 
core biopsy, in parallel with peripheral blood 
count analysis.IMAGING
• Radiography—assess kidneys and cardio -
pulmonary system.
• Abdominal ultrasonography—assess 
kidneys and adrenal glands.
• Echocardiography—evaluate for right-to-
left cardiac shunts.
• Bone marrow biopsy.
• Electrocardiography—assess heart disease.
• Retinal examination/ophthalmologic 
consult.
• Blood pressure measurement.
  TREATMENT
• Phlebotomy and concurrent replacement 
with intravenous isotonic fluids—to provide 
relief of signs during clinical crisis.
• Hydroxyurea—may temporarily decrease 
the RBCs and provide disease control.
• Consult a veterinary medical oncologist for 
most current recommendations and disease 
Hydroxyurea 40–50 mg/kg PO divided twice 
daily; titrate to response and toxicity (dog and 
cat).
N/A
  FOLLOW-UP
Periodic reexaminations with serial CBCs, 
retinal examinations, and serum biochemical 
profiles to monitor disease control and 
hydroxyurea side effects on bone marrow and 
other organs.
• CML = chronic myelogenous leukemia.
Prognostic markers for myeloid neoplasms: a comparative review of the literature and 
Weiss DJ, Aird B. Cytologic evaluation of 
primary and secondary myelodysplastic 
syndromes in the dog. Vet Clin Pathol 
2001, 30:67–75.

Canine and Feline, Seventh Edition  1107
PPolyneuropathies (Peripheral Neuropathies)
  BASICS
Diseases affecting peripheral motor, sensory, 
autonomic, and/or cranial nerves, in any 
• Inherited or acquired (degenerative, 
idiopathic, metabolic/endocrine, neoplastic/
paraneoplastic, immune-mediated inflamma-
tory, infectious, drugs/toxic). • Primary 
pathologic process—(1) axonal neuropathies , 
caused by either destruction or degeneration of 
neuronal cell bodies in dorsal root ganglia, 
ventral horn cells, or autonomic ganglia 
(neuronopathies) or axonal degenera  tion with 
secondary demyelination (axonopathies), or 
(2) demyelinating neuropathies  with primary 
demyelination due to disease of the Schwann 
cells or myelin sheath.
• Nervous—peripheral nervous system 
(occasionally also affecting CNS); possible 
involvement of the cranial nerves. • Other 
organ systems may be involved in the primary 
GENETICS
• Most inherited—autosomal recessive 
disorders. • Spinal muscular atrophy in 
Brittany spaniels, laryngeal paralysis in 
bouvier des Flandres—autosomal dominant.
• Inherited—rare. • Peripheral nerve 
involvement in metabolic and neoplastic 
diseases—incidence unknown. 
• Inflammatory—uncommon; coonhound 
paralysis (CHP) most frequent.
• CHP—North and Central America, parts 
of South America. • Distal denervating 
disease—dogs in UK; not reported elsewhere. 
• Dysautonomia—mostly dogs (occasionally 
cats) in Missouri, Oklahoma, and Kansas; cats 
in Scandinavia and UK.
Species
Breed Predilections—Inherited
Spinal Muscular Atrophy
• Brittany spaniel, Swedish Lapland dog, 
English pointer, German shepherd dog, 
Doberman pinscher, Rottweiler, griffon 
Briquet, Saluki, Maine Coon cats. • Progressive 
neuronopathy—Cairn terrier.
Axonopathies
• Giant axonal neuropathy—German 
shepherd dog. • Progressive axonopathy—
boxer. • Laryngeal paralysis—bouvier des 
Flandres. • Laryngeal paralysis/polyneuropathy 
complex—Dalmatian, Rottweiler, Pyrenean mountain dog. • Distal sensorimotor 
polyneuropathy—Rottweiler, Alaskan 
Malamute, Great Dane, Leonberger dog, 
bouvier des Flandres. • Progressive central and 
peripheral sensorimotor axonopathy—golden 
retriever. • Central-peripheral distal 
axonopathy—Birman cat. • Axonal 
neuropathy—Snowshoe cat. • Primary 
hyperoxaluria—domestic shorthair cats.
Demyelination
• Hypertrophic neuropathy—Tibetan 
mastiff. • Congenital hypomyelination 
neuropathy—golden retriever. 
• Demyelinating polyneuropathy–miniature 
schnauzers. • Recurrent demyelinating-
remyelinating polyneuropathy—Bengal cat.
Lysosomal Storage Diseases
• Globoid cell leukodystrophy—West Highland 
white terrier, Cairn terrier, domestic shorthair 
cats • Alpha- l-fucosidosis—English Springer 
spaniel. • Mannosidosis—Persian and domestic 
shorthair cats. • GM1 gangliosidosis type II—
Siamese and Korat cats. • Sphingomyelinosis 
(Niemann–Pick disease type A)—Siamese and 
Balinese cats. • Glycogenosis type IV—
Norwegian forest cat.
Sensory Neuropathy
• Longhaired dachshund, English pointer, 
German shorthaired pointer, English springer 
spaniels, French spaniels, Jack Russell terrier, 
border collies. • Ganglioradiculitis—Siberian 
husky.
Breed Predilections—Acquired
• CHP—higher incidence in coonhounds. 
• Clinical diabetic polyneuropathy—more 
common in cat than dog. • Insulinomas—
German shepherd dog, boxer, Irish setter, 
standard poodle, collie.
Inherited
• Often begin at <6 months of age. • Feline 
hyperchylomicronemia—1–8 months. 
• Feline hyperoxaluria—5–9 months. 
• Rottweiler, bouvier, Leonberger distal 
polyneuropathies— >1 year. • Giant axonal 
neuropathy in German shepherd dog—14–16 
months. • Intermediate and chronic forms of 
spinal muscular atrophy in heterozygote 
Brittany spaniel—6–12 months.
Acquired
• Secondary to neoplasia and insulinoma-
associated hypoglycemia—middle-aged to 
older animals. • Neospora caninum  
polyradiculoneuritis—usually dogs <6 
months of age. • Ganglioradiculitis— >1 year.
SIGNS
Inherited
• Most—progressive lower motor neuron 
(LMN) tetraparesis; generalized weakness, 
muscle tremors and atrophy, plantigrade/
palmigrade stance; stridor/voice change if laryngeal paralysis. • Sensory neuropathies—
self-mutilation (nociceptive deficits), mild to 
severe ataxia. • Lysosomal storage diseases—
slowly progressive CNS involvement (head 
tremors, ataxia, dysmetria, seizures, blindness, 
dementia) occur in conjunction with the LMN 
signs. • Sphingomyelinosis in cats—often 
present only with progressive motor and 
sensory neuropathy. • Giant axonal neuropathy 
of German shepherd dogs—rapidly progressive 
generalized weakness ( <3 weeks).
Acquired
• Rapid or slow progression. • Rapidly 
progressive course—initial stiff, stilted gait, 
leading to generalized LMN paresis or 
paralysis (CHP , distal denervating disease). 
• Slowly progressive course—generalized 
weakness and muscle atrophy; in distal 
polyneuropathies (diabetic neuropathy 
especially in cats), plantigrade/palmigrade 
stance. • Dysautonomia—primarily acute 
onset ( <48 hours) of depression, anorexia, 
regurgitation, vomiting, paralytic ileus, 
xerostomia, keratoconjunctivitis sicca (KCS), 
third eyelid protrusion, urinary incontinence. 
• Metabolic—owner reports non-neurologic 
clinical signs associated with weakness. 
• Paraneoplastic—primary tumor may be 
clinically silent at time of presentation or 
revealed on thoracic radiographs or 
abdominal ultrasound.
• Motor and sensorimotor—tetraparesis to 
tetraplegia, hyporeflexia to areflexia, 
hypotonia to atonia, and muscle atrophy 
classic; muscle tremors common. • Sensory—
proprioceptive deficits, hypoesthesia to 
anesthesia, without muscle atrophy or 
hyporeflexia (except in boxers); sensory ataxia. 
• Paraesthesia—feline diabetic neuropathy, 
sensory neuropathies. • Hypothyroidism—
may be associated with generalized poly -
neuropathy, laryngeal and/or facial nerve 
paralysis, megaesophagus, and vestibular signs. 
• Lysosomal storage diseases—hepatospleno-
megaly common. • Paraneoplastic—may find 
evidence of neoplasia. • Dysautonomia—dry 
nose, KCS, bradycardia, anal areflexia. 
• Primary hyperchylomicronemia (cats)—
lipid granulomata, which can be palpated 
under the skin and abdomen. • Primary 
hyperoxaluria (cats)—enlarged, painful kidneys 
on palpation. • Cranial nerve abnormalities 
(including dysphonia/aphonia)—variable.
CAUSES
Acquired
• Immune-mediated—primary or secondary; 
may be seen with systemic lupus erythematosus 
(SLE), glomerulonephritis, polyarthritis. 
• Metabolic/endocrine—diabetes mellitus 
(cats), hypothyroidism, hyperadrenocorticism. 
• Neoplastic/paraneoplastic—insulinoma, 
carcinomas, malignant melanoma, mast cell 
tumor, osteosarcoma, multiple myeloma,

1108  Blackwell’s Five-Minute Veterinary Consult  
Plymphosarcoma. • Infectious— N. caninum,  
feline leukemia virus (FeLV), feline immuno -
deficiency virus (FIV). • Chemotherapy 
drugs—vincristine, vinblastine, cisplatin. 
• Toxic—thallium, organophosphates, 
salinomycin (cats), lasalocid (dogs). • Idiopathic.
Development of specific diseases (metabolic, 
immune, neoplastic) or exposure to specific 
drugs/toxins or causal factors (raccoon saliva).
  DIAGNOSIS
• Acute—botulism; tick paralysis; fulminant 
myasthenia gravis; acute multifocal 
myelopathies. • Chronic—polymyopathy; 
chronic multifocal myelopathies.
• Standard laboratory tests—often normal; 
may indicate underlying metabolic or 
neoplastic disease. • High serum creatine 
kinase—indicates an accompanying 
myopathy or diagnosis of polymyopathy.
• Antinuclear antibody, Coombs’ test—if 
immune disease suspected. • Low total 
thyroxine (T4), low free T4, and high 
endogenous thyroid-stimulating hormone 
(TSH)—  hypothyroidism. • Amended insulin: 
glucose ratio >30—supports the diagnosis of 
insulinoma. • Serology—assists in the 
diagnosis of N. caninum,  FIV, FeLV infection. 
• Diminished lysosomal enzyme activity in 
leukocytes, cultured fibroblasts—lysosomal 
storage diseases. • Pharmacologic testing 
(pilocarpine ophthalmic drops, bethanechol 
challenge)—dysautonomia. • High serum 
cholesterol and triglycerides, low lipoprotein 
lipase—  hyperchylomicronemia. • Oxalate 
and/or l-glyceric acid in urine—primary 
hyperoxaluria. • Monoclonal gammopathy—
IMAGING
Thoracic and abdominal radiographs—search 
for a neoplastic cause; megaesophagus, ileus, 
bladder atony, constipation, and delayed 
gastric emptying in dysautonomia.
• Electrophysiology (EMG, motor and 
sensory nerve conduction studies ventral and 
dorsal nerve root studies)—cornerstone for 
diagnosis. • Lumbar CSF analysis—valuable in 
diagnosing nerve root involvement. • Muscle 
biopsy—confirms denervation. • Peripheral 
nerve biopsy (distal)—further characterizes 
Lesion distribution along peripheral nerves 
(proximal, distal, widespread) and degree of 
axonal degeneration, demyelination, and/or neuronal cell body degeneration depends on 
the specific condition present.
  TREATMENT
• Usually outpatient. • Inpatient—observe 
dogs with CHP closely for respiratory failure 
in early progressive phase of disease.
• Dysautonomia—may require IV fluid 
therapy and/or parenteral feeding. • Physical 
therapy.
DIET
• Generally no special management, unless 
megaesophagus or dysphagia occurs. 
• Hyperchylomicronemia—low-fat diet 
alone can resolve the polyneuropathy in 2–3 
months. • Paralysis—ensure patient can 
reach food and water. • Regurgitation and/
or vomiting—temporarily halt oral intake; 
consider gastrostomy tube. • Diabetes 
mellitus—monitor food intake; in cats, feed 
a low-carbohydrate, high-protein diet; 
diabetic neuropathy often reversible with 
• T reatment of primary cause may not lead to 
reversal of signs; in some cases, deterioration 
will continue. • Canine axonal degeneration—
progressive deterioration.
• Inherited—most untreatable. • Acquired—
treat primary cause with the hope that the 
secondary polyneuropathy improves or 
resolves; not always successful. • Chronic 
relapsing demyelinating neuropathy—most 
likely of immune origin; may improve with 
long-term immunosuppressive therapy 
(prednisone, azathioprine, cyclophosphamide); 
response of individual patient variable. 
• SLE-related—treat as for chronic relapsing 
polyneuropathy. • Neoplasia—treat primary 
neoplasia. • Neospora- associated 
 polyradiculoneuritis—clindamycin combined 
with pyrimethamine. • Dysautonomia—
treat symptomatically with IV fluids, artificial 
tears, metoclopramide, bethanechol (cats, 
0.5–2.5 mg SC q12h or 2.5–10 mg PO 
q6–8h; dogs, 0.5–15 mg SC q12h or 2.5–30 
mg PO q6–8h), and pilocarpine eye drops.
Corticosteroids—contraindicated in 
Neospora -associated polyradiculoneuritis, 
hyperadrenocorticism, and CHP .  FOLLOW-UP
Repeat neurologic examinations.
• Avoid breeding patients with Neospora  
(placental transfer of the organism from the 
bitch). • Avoid contact with raccoons. 
• Avoid future vaccinations if suspected 
associated with vaccines.
Continued neurologic deterioration leading to 
inability to ambulate, severe muscle atrophy, 
pressure sores, urinary tract infection, muscle 
fibrosis, aspiration pneumonia.
• Demyelinating conditions—more rapid 
improvement than axonal neuropathies 
(majority), which can take months for partial 
or complete recovery, if at all. • Inherited—
most have a poor prognosis (except 
hyperchylomicronemia in cats). • Acute 
polyradiculoneuritis (CHP)—good long-term 
prognosis; may take weeks to months to 
recover. • Metabolic—fair-to-good prognosis 
with successful treatment of primary metabolic 
abnormality; insulinomas have high recurrence 
rate. • Other acquired—most show continued 
deterioration despite treatment.
Immunosuppressive agents—contraindicated.
• CHP = coonhound paralysis. • EMG = 
electromyography. • FeLV = feline leukemia 
virus. • FIV = feline immunodeficiency virus. 
• LMN = lower motor neuron. • KCS = 
keratoconjunctivitis sicca. • SLE = systemic 
lupus erythematosus. • T4 = thyroxine. 
vetneuromuscular.ucsd.edu
Dewey CW, Cerda-Gonzalez S. Disorders of the 
peripheral nervous system: mononeuropathies 
and polyneuropathies. 2nd ed. Ames, IA: 
Wiley-Blackwell, 2008, pp. 427–467.
Granger N. Canine inherited motor and 
sensory neuropathies: an updated 
classification in 22 breeds and comparison 
to Charcot-Marie-Tooth disease. Vet J 
2011, 188:274–285.
Author  Paula Martín Vaquero
available onlinePolyneuropathies (Peripheral Neuropathies)  (continued)

Canine and Feline, Seventh Edition  1109
PPolyphagia
  BASICS
Increased food intake.
• Failure to assimilate or loss of nutrients 
(e.g., maldigestion/malabsorption 
syndromes such as exocrine pancreatic 
insufficiency).
• Inability to use nutrients (e.g., diabetes 
mellitus, poor-quality diets, gastrointestinal 
parasites).
• Hypoglycemia (e.g., insulinoma, insulin 
overdose).
• Increased metabolic rate or demand (e.g., 
hyperthyroidism, cold environments, 
pregnancy, lactation).
• Psychologic or learned behaviors (e.g., 
palatable diets, competition with other 
household pets).
• Iatrogenic (e.g., drugs such as anticon -
vulsants or glucocorticoids).
• Genetic (e.g., Labrador and flat-coated 
retrievers).
• Cardiovascular—obesity can worsen clinical 
• CNS—tumors of the brain, especially of 
the hypothalamus, can cause polyphagia.
• Integument—obese animals, especially cats, 
are susceptible to dermatitis.
• Musculoskeletal—overweight patients are 
susceptible to arthritis and other orthopedic 
problems.
• Respiratory—obesity exacerbates dyspnea 
in patients with respiratory disease.
• Some dog breeds are prone to obesity: 
beagle, Rottweiler, cocker spaniel, dachshund, 
Shetland sheepdog, dalmation, and the 
SIGNS
• Eating more frequently and/or a greater 
quantity than normal.
• Excessive food-seeking and food-stealing 
behaviors.
• Weight loss may occur with certain disease 
states (e.g., exocrine pancreatic insufficiency, 
diabetes mellitus, hyperthyroidism).
• Polyuria/polydipsia (PU/PD) occurs in 
some patients (diabetes mellitus, hyper -
thyroidism, hyperadrenocorticism).
Patients may have excessive body fat, but 
those with an underlying medical problem 
(e.g., exocrine pancreatic insufficiency, 
diabetes mellitus, hyperthyroidism) may 
be thin.CAUSES
Physiologic
• Growth.
• Response to a cold environment.
• Increased exercise.
• Genetic predispositions:
◦ 14-bp deletion in the pro-opiomelanocortin 
(POMC ) gene of Labrador and flat-coated 
retrievers leading to increases in obesity, 
adiposity, and food motivation.
◦ Polymorphism in the melanocortin 4 
receptor gene ( MC4R : c.92C>T) 
predisposing obese cats to development of 
Pathologic
• Hyperadrenocorticism—dogs.
• Insulin overdose.
• Growth hormone-secreting pituitary 
tumor.
• Lymphocytic plasmacytic enteritis in 
cats—uncommon.
• Neoplasms of the brain—rare.
• Gastrointestinal neoplasms—rare.
• Compulsive polyphagia—rare.
Iatrogenic
• Progestins.
• Benzodiazepines.
• Anticonvulsants.
• Palatable food.
• Free feeding/overfeeding.
• Poor diet.
• Competition for food.
• Lower income owners.
• Older age of the patient.
• Older age of the owner.
• Female spayed > male neutered > intact 
  DIAGNOSIS
PU/PD (excessive trips to food/water area)—
differentiate by observation.
• Neutrophilia, monocytosis, lymphopenia, 
and eosinopenia with hyperadrenocorticism, 
and in patients receiving corticosteroids.
• Hyperglycemia with diabetes mellitus, 
growth hormone-secreting pituitary tumors (cats, insulin-resistant diabetes mellitus), and 
• Hypercholesterolemia with recent food 
intake, hyperadrenocorticism, and diabetes 
mellitus, and in patients receiving 
• High alkaline phosphatase and alanine 
aminotransferase activity with hyperadreno -
corticism (dogs), hyperthyroidism (cats), and 
diabetes mellitus, and in patients receiving 
• Hypoproteinemia with protein-losing 
enteropathies (e.g., lymphangiectasia, 
inflammatory bowel disease).
• Hypoglycemia in patients with insulinoma 
or insulin overdose.
• Low urine specific gravity with diabetes 
mellitus, diabetes insipidus, hyperthyroidism, 
and hyperadrenocorticism, and in patients 
receiving corticosteroids.
• Glucosuria, possibly ketonuria, with 
• Fecal examination to rule out gastro -
• Total serum T4 to rule out hyperthyroidism 
(cats); T3 suppression testing if hyperthyroidism 
is suspected but serum total T4 is normal.
• Low-dose dexamethasone suppression or 
stimulation test to diagnose hyperadreno -
corticism; plasma ACTH level or high-dose 
dexamethasone suppression testing to 
differentiate pituitary-dependent hyperadreno -
corticism from adrenal tumor if hyperadreno-
corticism is confirmed with the low-dose 
dexamethasone suppression test or ACTH 
• Serum insulin levels in hypoglycemic 
patients to rule out insulinoma.
IMAGING
• Abdominal radiology may demonstrate 
hepatomegaly associated with hyperadreno -
corticism, diabetes mellitus, and corticosteroid 
• Abdominal ultrasonography may 
demonstrate an adrenal mass or bilateral 
adrenomegaly (hyperadrenocorticism), 
hepatomegaly (hyperadrenocorticism, 
diabetes mellitus, and corticosteroid 
administration), bowel wall thickening or 
bowel wall layering disruption (inflammatory 
bowel disease, lymphoma, lymphangiectasia), 
and pancreatic masses (insulinoma).
• MRI could be used to visualize a neoplasm 
of the hypothalamus.
Endoscopy with biopsy of the upper 
gastrointestinal tract to rule out 
gastrointestinal diseases.

1110  Blackwell’s Five-Minute Veterinary Consult  
• Usually outpatient medical management.
• Polyphagia without weight gain or with 
weight loss is more likely due to a medical 
problem; evaluate the animal prior to food 
restriction or manipulation.
• Once pathologic causes of polyphagia have 
been excluded, limit the amount of food 
available, feed a reduced-calorie diet, and/or 
increase exercise if obesity or weight gain is 
present:
◦ Owners must measure food to accurately 
assess intake.
◦ Gram scale measuring provides best 
accuracy.
◦ Some dogs may benefit by the addition 
of low-calorie bulky foods such as canned 
or frozen green beans.
◦ Feeding smaller meals 2–3 times daily 
may be beneficial for some patients, 
provided the total food provided remains 
the same as required by life stage and 
activity to promote weight loss or prevent 
◦ Removing the pet during human meal 
preparation and consumption to reduce 
begging behavior and the pet obtaining 
additional food.
• Slowing down the rate of eating may be 
beneficial in some dogs, using food-
dispensing toys that require manipulation to 
obtain daily ration.
• If social issues within the home influence 
intake these must be addressed:
◦ Feed all dogs in separate locations, 
preferably without visual contact.
◦ Have multiple feeding stations available 
in a multiple-cat home.
• The average animal’s daily caloric need can be 
estimated by the formula 30 × weight (kg) + 70:
◦ Alternatively, using the website https://
petnutritionalliance.org/ can provide 
clinicians with the ability to quickly 
calculate necessary weight loss and feeding 
amounts based on specific diet being fed.
• Chew toys can be used as a substitute for 
food and desires for mastication.• Dietary options:
◦ High fiber, high protein diets provide 
greater satiety and reduce begging behavior 
(e.g., Royal Canin Veterinary Diet® Canine 
and Feline Satiety® Support).
◦ Metabolism-increasing diets naturally 
increase metabolic rate (e.g., Hill’s® Prescription 
Diet® Metabolic Canine and Feline).
• See specific diseases for detailed therapy.
• Drug-induced—attempt to taper or 
discontinue drug.
• If a compulsive eating disorder is suspected 
in dogs, clomipramine 1–3 mg/kg PO q12h 
or fluoxetine 1–2 mg/kg q24h may be used or 
in cats clomipramine 0.25–1.0 mg/kg q24h 
or fluoxetine 0.5–1.0 mg/kg q24h.
  FOLLOW-UP
• Monitor body weight in patients with 
nonpathologic causes of polyphagia.
• Assess compliance with feeding regime and 
food measurement to decrease intake and 
promote weight loss.
• Obesity in nonpathologic polyphagia.
• Owner compliance:
◦ Owner responds to begging behavior and 
caloric intake is not decreased.
◦ Owner does not factor treats or additives 
into daily caloric count.
• Weight loss/emaciation in pathologic causes 
of polyphagia.
• Worsening of respiratory or cardiovascular 
disease processes in obese patient.
• Difficulty achieving level of appropriate 
exercise due to respiratory, cardiovascular, or 
musculoskeletal diseases.
• Decreased metabolic rate after spaying/
neutering.
• Increased resource guarding behaviors.• Increased irritability and aggression.
• Anesthetic complications associated with 
obesity and adiposity.
Obesity
A normal physiologic response to pregnancy.
SYNONYMS
• Eating disorder.
• Hyperphagia.
SEE ALSO
• Coprophagia and Pica.
• Obesity.
Courcier EA, Thomson RM, Mellor DJ, Yam 
PS. An epidemiological study of 
environmental factors associated with 
canine obesity. J Small Anim Pract 2010, 
51(7):362–367.
Houpt KA. Ingestive behavior: food and 
water intake. In: Domestic Animal 
Behavior, 5th ed. Ames, IA: Wiley-
Blackwell, 2011, pp. 235–270.
Luescher AU. Diagnosis and management of 
compulsive disorders in dogs and cats. Vet 
33(2):253–267.
Savidge C. Polyphagia. In: Cote E, ed., 
Clinical Veterinary Advisor Dogs and Cats, 
3rd ed. St. Louis, MO: Mosby, 2014, pp. 
826–828.
Katherine A. Houpt.Polyphagia  (continued)

Canine and Feline, Seventh Edition  1111
P
Polypoid Cystitis
  BASICS
OVERVIEW
A chronic inflammatory condition of the 
urinary bladder characterized by villous or 
polypoid protrusions from the mucosa and 
associated with chronic infectious or 
noninfectious causes. Also called proliferative 
cystitis. Polypoid projections are diffusely 
located over the luminal surface of the 
bladder. It is unclear if proliferative urethritis 
is a separate disease with different causes. If 
polyps erode and ulcerate, varying degrees of 
hematuria and dysuria occur. The gross 
appearance of polyps cannot be distinguished 
from that of bladder neoplasms, such as 
transitional cell carcinomas (TCCs), without 
histological evaluation.
• Dogs with chronic urinary tract infection 
(UTI)s or urolithiasis.
• No cases reported in cats.
SIGNS
• Initially, may be asymptomatic.
• Hematuria is the most common sign.
• Gross hematuria often occurs at the end of 
the micturition stream during maximal 
bladder contraction.
• Pollakiuria and dysuria may also be present 
and are associated with irritation of the 
polyps.
• Urethral obstruction could occur if a 
sufficient number of bladder polyps are 
located in the trigone of the bladder. Polyps 
originating or in the urethra may also cause 
partial or total obstruction.
• Ureteral obstruction may occur if polyps 
surround the ureteral orifice.
• UTI may be present concurrently, which 
can predispose to upper UTI.
• Causes of polypoid cystitis in dogs have not 
been well documented, but this disorder is 
commonly associated with UTI, urolithiasis, 
and other types of chronic irritation.
• Chronic infection and inflammation 
secondary to long-term indwelling transurethral 
urinary catheters and urinary stents have been 
associated with polypoid cystitis.
  DIAGNOSIS
• Polypoid cystitis should be ruled out in 
cases of hematuria, pollakiuria, dysuria, and 
recurrent UTI.
• Bladder neoplasms (such as TCC), UTI, 
and urolithiasis are the most common 
rule-outs.CBC/BIOCHEMISTRY/URINALYSIS
• Serum biochemistry profiles should be 
normal in most cases of polypoid cystitis 
unless azotemia occurs as a result of 
obstruction to urine outflow and/or 
• Urinalysis may reveal hematuria, pyuria, 
and transitional epithelial cells.
• Urine should be cultured by clean 
midstream collection, clean catheterization or 
at the time of cystoscopy. Culture by 
cystocentesis is also appropriate once TCC 
has been ruled out. This will prevent potential 
spread of TCC along the needle track.
• Representative polyps removed via cysto -
scopy or cystotomy should be preserved in 
formalin for light microscopic examination.
• An adequate sample of bladder tissue 
should be placed in culture media suitable for 
growth of microbes, preferably prior to 
antibiotic administration.
• Survey radiographs may reveal a normal 
bladder, an irregular thickening of the surface 
contour of the bladder, and/or concurrent 
• Double-contrast cystography or positive-
contrast cystography may reveal irregular 
polypoid fronds projecting in the bladder 
lumen and/or a thickened bladder wall. The 
most common location of involvement is the 
cranioventral bladder wall. Single large polyps 
with a narrow or broad base may be observed 
scattered throughout the contrast puddle. 
Uroliths will migrate to the most dependent 
portion of the contrast puddle.
• Ultrasonography may show polyps scattered 
along the mucosal surface of the bladder, 
especially in the cranioventral aspect.
• Cystoscopic or ultrasound-guided biopsy 
may be used to obtain representative portions 
of the polyps for light microscopic exam -
ination of stained sections of the lesions.
• More invasive, full-thickness biopsy of the 
wall of the bladder via cystotomy may be 
required to include the base of the polyps 
with an adequate margin of healthy tissue.
• Gross changes involving the mucosal 
surface of the urinary bladder include single 
or multiple small masses ranging from 1 to 10 
mm in size. The masses may be nodular with 
a broad base or attached to the bladder wall 
by a thin stalk.
• Light microscopic changes include polypoid 
projections of hyperplastic epithelium that 
surround a core of proliferative connective tissue 
mixed with acute and chronic inflammation 
(congestion, edema, and acute and chronic 
inflammatory cells). Findings characteristic of 
malignancy (e.g., dispro  portionate enlargement 
of nuclei in relation to the cytoplasm; increase 
in chromatin content causing hyperchromasia; structural changes such as aberrant chromatin 
patterns, lack of distinct cell boundaries, 
irregularity in cell outlines; enlargement and/or 
increase in number of nuclei; multinucleated 
cells with atypical nuclei; abnormal number of 
mitotic figures; cytoplasmic inclusions and 
vacuolization; invasion of basement membranes) 
are conspicuously absent. Eosinophils have been 
present; their significance is unknown. In some 
patients, changes typical of granulomatous 
inflammation predominate.
• Fluorescence in situ hybridization identifies 
bacteria when urine and tissue culture was 
negative.
  TREATMENT
• Elimination of bacteria that are a source of 
chronic irritation is a rational therapeutic goal.
• Nonsurgical removal of urocystoliths 
(voiding urohydropropulsion, lithotripsy, 
dietary management) that are causing chronic 
irritation may result in elimination of 
inflammatory polyps.
• The polyps can be removed nonsurgically 
(stone basket extraction, laser ablation, 
electrocautery via cystoscopy or surgically via 
cystotomy).
• Partial cystectomy may be required to remove 
polyps affecting large portions of the bladder. 
The remaining portion of the urinary bladder 
may return to normal size in 3–6 months.
• Select an antimicrobic based on culture of 
urine and polyp tissue. Optimal duration of 
antibiotic therapy is unknown. Post-therapy 
urine cultures can be used to determine if 
longer courses of antimicrobs are needed.
• Use of piroxicam and immunosuppressive 
drugs are suggested, but efficacy is variable.
  FOLLOW-UP
• A urine culture should be performed 7–10 
days after antimicrobial therapy is initiated, 
to confirm urine sterility. Follow-up urinalysis 
and urine cultures should also be performed 
by cystocentesis 7 days after antimicrobial 
therapy has ceased and 1 month post therapy.
• Ultrasonographic reevaluation of the urinary 
tract is recommended at 1, 3, and 6 months.
• Persistent asymptomatic polyps are not 
treated.
Control of predisposing factors such as UTI, 
urolithiasis, urinary stenting.

1112  Blackwell’s Five-Minute Veterinary Consult  
PPOSSIBLE COMPLICATIONS
• Chronic UTIs.
• Upper UTI.
• Complete obstruction of ureters or urethra.
• The expected course is favorable and the 
prognosis good if the underlying cause is 
treated and eradicated.
• Rarely patients with polypoid cystitis 
develop TCC several years after initial 
diagnosis. It is unknown if some of these cases 
represent early carcinoma in situ .
• Urolithiasis.AGE-RELATED FACTORS
No age-related factors have been 
reported, but usually not found in 
immature dogs.
SEE ALSO
• T ransitional Cell Carcinoma.
• TCC = transitional cell carcinoma.
Cooper JE, Brearley MJ. Urothelial 
abnormalities in the dog. Vet Rec 1986, 
118:513–514.
Johnston SD, Osborne CA, Stevens JB. 
Canine polyploid cystitis. J Am Vet Med 
Assoc 1975, 166:1155–1160.Martinez I, Matton JS, Eaton KA, et al. 
Polypoid cystitis in 17 dogs (1978–2001). 
J Vet Intern Med 2003, 17:499–509.
Tagiguchi M, Inaba M. Diagnostic 
ultrasound of polypoid cystitis in dogs. 
J Vet Med Sci 2005, 67(1):57–61.
A. Osborne.Polypoid Cystitis  (continued)

Canine and Feline, Seventh Edition  1113
PPolyuria and Polydipsia
  BASICS
• Polyuria (PU)—increased urine production 
(dogs, >45 mL/kg/day; cats, >40 mL/kg/day).
• Polydipsia (PD)—increased water 
consumption (dogs, >90 mL/kg/day; cats, 
>45 mL/kg/day).
• The volumes of urine produced and water 
consumed are controlled by interactions 
between the kidneys, pituitary gland, and 
hypothalamus through monitoring of plasma 
osmolality. Volume receptors within the atria 
and aortic arch also influence thirst and urine 
production. PU may occur when the quantity 
of functional antidiuretic hormone (ADH) 
synthesized in the hypothalamus or released 
from the posterior pituitary is limited, or 
when the kidneys fail to respond normally to 
ADH. PD occurs when the thirst center in 
the anterior hypothalamus is stimulated.
• In most PU patients, plasma becomes 
relatively hypertonic and activates thirst 
mechanisms; the PD maintains hydration as a 
compensatory response. Occasionally PD is the 
primary process and PU is compensatory. In 
this case, the patient’s plasma becomes relatively 
hypotonic because of excessive water intake, 
ADH secretion is reduced, resulting in PU.
• Urologic—full bladder.
• Cardiovascular—circulating volume.
• Endocrine/metabolic—pituitary gland, 
hypothalamus play a role in compensation to 
PU or PD.
• Congenital diseases in many breeds (e.g., 
central diabetes insipidus [CDI], nephrogenic 
diabetes insipidus [NDI], portovascular 
anomaly, kidney disease).
• Kidney disease, hyperadrenocorticism 
(HAC), hyperthyroidism, neoplasia affecting 
the pituitary or hypothalamus predominantly 
affect middle-aged and older animals.
CAUSES
• Primary PU due to impaired kidney 
response to ADH—kidney disease, HAC, 
hyperthyroidism, pyelonephritis, 
leptospirosis, pyometra, hepatic failure, 
hypercalcemia, hypokalemia, kidney 
medullary solute washout, dietary protein 
restriction, drugs, congenital NDI.
• Primary PU caused by osmotic diuresis—
diabetes mellitus (DM), primary kidney 
glucosuria, postobstructive diuresis, some 
diuretics (e.g., mannitol and furosemide), 
ingestion or administration of large quantities 
of solute (e.g., sodium chloride or glucose), 
and hypersomatotropism.• Primary PU due to ADH deficiency—
idiopathic, traumatic, neoplastic, or 
congenital CDI; some drugs (e.g., alcohol 
and phenytoin).
• Primary PD—behavioral, pyrexia, pain, 
organic disease of the anterior hypothalamic 
thirst center of neoplastic, traumatic, or 
inflammatory origin.
• Kidney, liver and/or endocrine disease.
• Administration of diuretics, corticosteroids, 
anticonvulsants.
• Low-protein diets.
  DIAGNOSIS
Differentiating Similar Signs
• Differentiate PU from pollakiuria. 
Pollakiuria: often associated with dysuria, 
stranguria, hematuria. Patients with PU void 
large quantities of urine; patients with 
pollakiuria frequently void small quantities of 
urine. Confirm PU/PD by measuring 
24-hour water intake and urine output (3- to 
5-day collection period preferred).
• Urine specific gravity (USG) measurement 
may provide evidence of hypersthenuria 
(dogs, >1.030; cats, >1.035), ruling out 
persistent PU/PD.
Differentiating Causes
• Kidney disease, HAC, DM, 
• Progressive weight loss—consider chronic 
kidney disease, DM, hyperthyroidism, 
hepatic failure, pyometra, pyelonephritis, 
hypoadrenocorticism, malignancy-induced 
• Decreased appetite—consider kidney 
disease, pyelonephritis, malignancy-induced 
hypercalcemia, hepatic disease, hypoadreno- 
• Polyphagia—consider DM, 
hyperthyroidism, HAC, acromegaly.
• Bilateral alopecia or other cutaneous 
problems—consider HAC, endocrinologic 
disorders
• Uremic breath and stomatitis—consider 
advanced kidney disease.
• Vomiting—consider kidney disease, 
hypoadrenocorticism, pyelonephritis, hepatic 
failure, hypercalcemia, hypokalemia, hyper -
thyroidism, DM.
• Malaise and/or weakness—kidney disease, 
hypoadrenocorticism, pyometra, hyper -
calcemia, DM, hepatic disease, hypokalemia, 
HAC.
• Palpable thyroid nodule—consider 
• Hypertensive retinopathy—consider 
chronic kidney disease (CKD), 
hyperthyroidism, DM, HAC.• Recent estrus (previous 2 months) in a 
middle-aged intact female—consider 
pyometra.
• Abdominal distention—consider hepatic 
failure, HAC, pyometra, nephrotic 
syndrome.
• Lymphadenopathy, anal sac mass or other 
neoplastic process—consider hypercalcemia 
• Behavioral or neurologic disorder—
consider hepatic failure, primary PD, CDI.
• Marked PD (patients almost continuously 
seek and consume water)—consider primary 
PD, CDI, NDI.
• Consider drug-induced (steroids, diuretics, 
anticonvulsants) PU/PD.
• Consequence of urolith prevention/
dissolution or high salt diet.
Key point:  PU/PD may be the first symptom 
of many diseases.
• Urinalysis is useful to confirm PU, 
discriminate water diuresis from solute diuresis, 
and identify urinary tract infection (UTI).
• Serum sodium concentration or osmolality 
may help differentiate primary PU from PD. 
Measuring serum osmolality is preferred; 
calculated serum osmolality is not an 
acceptable alternative.
• Relative hypernatremia or high serum 
osmolarity suggests primary PU.
• Hyponatremia or low serum osmolarity 
suggests primary PD, except in animals with 
hypoadrenocorticism, which have hypo -
natremia and primary PU.
• Azotemia is typical of kidney causes for 
PU/PD, but may also indicate dehydration 
resulting from inadequate compensatory PD.
• Unexpectedly low BUN concentrations 
suggest hepatic failure.
• With high hepatic enzymes, consider HAC, 
hyperthyroidism, hepatic failure, pyometra, 
DM, or administration of drugs (e.g., anti -
convulsants and corticosteroids).
• Persistent hyperglycemia suggests DM.
• Hyperkalemia, particularly if associated 
with hyponatremia, suggests hypoadreno -
corticism or therapy with potassium-sparing 
diuretics.
• Hypercalcemia induces PU only when it 
results from increased ionized calcium (not 
protein-bound calcium) concentration.
• Hypoalbuminemia supports kidney or 
hepatic causes of PU/PD.
• Neutrophilia is consistent with 
pyelonephritis, pyometra, HAC, 
corticosteroid administration.
• USG values 1.001–1.003 suggest primary 
PD, CDI, and congenital NDI.
• Glucosuria supports a diagnosis of DM or 
kidney glucosuria.
• Pyuria, white blood cell casts, and/or 
bacteriuria should prompt consideration of 

1114  Blackwell’s Five-Minute Veterinary Consult  
• ACTH stimulation or dexamethasone 
suppression tests rule out HAC.
• Thyroxine concentration to rule out 
• Bile acids (fasting and postprandial) to rule 
out portosystemic shunt or hepatic failure.
• Urine culture—chronic pyelonephritis 
cannot be conclusively excluded by absence of 
pyuria or bacteriuria.
• Cytology from lymph node aspirate may 
diagnose lymphoma, which induces PU by 
hypercalcemic nephrotoxicity or direct 
infiltration of kidney tissues.
• Paired Leptospira  titer to rule out 
leptospirosis.
• ADH response test to rule out CDI.
• Water deprivation testing (see Diagnostic 
Procedures) is controversial due to 
dehydration risk; use selectively.
IMAGING
Abdominal survey radiography, ultrasono -
graphy: may provide evidence of kidney, 
hepatic, adrenal, or uterine disorders that can 
cause PU/PD.
Modified Water Deprivation with ADH 
Response Test
• Differentiates CDI from primary PD and 
NDI. Rule out other causes for PU/PD before 
performing this test. Controversial, some 
suggest omitting water deprivation and 
proceeding directly to ADH administration to 
rule in CDI, however administration of ADH 
to patients with primary PD may be dangerous.
• Contraindicated in dehydrated and 
azotemic patients; ADH response testing may 
be performed safely in these patients.
• Patients that concentrate urine adequately in 
response to water deprivation have adequate 
ADH production and kidney response to 
ADH. If other causes have been ruled out, 
primary PD is presumed to be present.
• Failure to concentrate urine adequately in 
response to properly designed water 
deprivation tests, but forming concentrated 
urine in response to administration of 
exogenous ADH = CDI.
response to water deprivation and also failure 
to further concentrate urine in response to 
administration of exogenous ADH = NDI.
  TREATMENT
• Serious medical consequences are rare if 
patient has free access to water and is able to drink. Until the mechanism of PU is 
understood, discourage owners from limiting 
access to water. Direct treatment at the 
• Provide PU patients with free access to 
water unless they are vomiting. If vomiting, 
give replacement maintenance fluids 
parenterally after appropriate samples have 
been collected for initial diagnostics. Provide 
fluids parenterally when other conditions 
limit oral intake or dehydration persists 
despite PD.
• Base fluid selection on the underlying 
cause for fluid loss; lactated Ringer’s solution 
is acceptable for most patients.
• When dehydration has resulted from 
withholding water, or when urine is 
hyposthenuric, providing oral water or 
parenteral administration of dextrose 5% in 
water may be preferred to lactated Ringer’s 
solution.
• Primary PD—treat by gradually limiting 
water intake to a normal daily volume. May 
be necessary to reduce water intake over 
days–weeks to avoid undesirable behavior 
such as barking, urine consumption, or other 
bizarre behavior. Monitor patient closely to 
avoid iatrogenic dehydration. Salt (1 g/30 kg 
q12h) or sodium bicarbonate (0.6 g/30 kg 
q12h) may be given orally to help reestablish 
kidney medullary solute gradient. Consider 
behavior modification if water restriction 
alone is unsuccessful.
Do not withhold water from patients with 
PU because potentially dangerous 
dehydration may result.
Do not administer ADH to patients 
with primary PD due to risk of inducing 
water intoxication (hyponatremia, hypo -
osmolality, and neurologic complications).
Until kidney disease and hepatic failure have 
been excluded as potential causes for PU/PD, 
use caution in administering any drug 
eliminated via these pathways.  FOLLOW-UP
• Hydration status—assessment of hydration, 
serial evaluation of body weight.
• Fluid intake and urine output provide a 
useful baseline for assessing response to therapy.
Dehydration, hypovolemic shock, 
• Bacterial UTI.
• Urinary incontinence may develop in dogs 
with concurrent urethral sphincter 
dysfunction, presumably because of increased 
bladder filling associated with PD.
SEE ALSO
Diseases.
• Diabetes Mellitus.
• CDI = central diabetes insipidus.
Consulting Editor  J.D. Foster 
available onlinePolyuria and Polydipsia  (continued)

Canine and Feline, Seventh Edition  1115
PPortosystemic Shunting, Acquired
  BASICS
OVERVIEW
develop subsequent to portal hypertension 
(PH) and involve complex physiology 
aberrations and adaptations; experimentally 
form 5–14 weeks after onset of PH.
• Prehepatic PH—compromised perfusion 
through abdominal portion of the portal vein.
• Intrahepatic PH—classified as presinusoidal, 
sinusoidal, postsinusoidal causes.
• Posthepatic PH—rostral to hepatic vein; 
cardiac, pericardial, or major vein causes.
• APSS evolve from preexisting remnant 
vessels and the process of angiogenesis.
• APSS common in dogs and cats but differ 
in location from the clinically symptomatic 
esophageal APSS common in humans; 
common APSS in dogs and cats involve 
communications between left gonadal 
remnants vessels, the left renal vein, and 
splenic veins with the caudal vena cava.
• Most common—in dogs with chronic 
necroinflammatory liver disease.
• Less common—in dogs with ductal plate 
malformations (DPM, congenital hepatic 
fibrosis [CHF] phenotype), rare noncirrhotic 
portal hypertension (NCPH), recovery from 
severe panlobular necrosis, dogs with porto­
systemic vascular anomaly (PSVA) intolerant 
to surgical shunt attenuation, or dogs simply 
with severe portal vein hypoplasia/atresia.
• APSS in cats—DPM with CHF phenotype, 
severe CCHS (rare), or PSVA intolerant to 
surgical shunt attenuation (severe portal 
hypoplasia) or rarely just severe portal vein atresia.
• Certain disorders—have age or breed 
incidence (see Ductal Plate Malformation 
(Congenital Hepatic Fibrosis); Cirrhosis and 
Fibrosis of the Liver; Hepatitis, Chronic).
• Breeds—DPM more common in domestic 
longhair, Persian and Himalayan cats, boxer dogs 
but may affect any pure ­ or mixed ­breed dog.
SIGNS
• Clinical signs—sequelae of PH, impaired 
hepatic perfusion, and hepatofugal circulation 
(hepatofugal = splanchnic portal circulation 
away from the liver) with or without or 
reduced hepatic function depending on cause.
• Ascites—common but variable; often 
fluctuates in severity.
• APSS may associate with episodic hepatic 
encephalopathy (HE)— may manifest as 
neurobehavioral or neurocognitive abnormali ­
ties, amaurotic blindness, polyuria/polydipsia 
(PU/PD), anorexia, lethargy, vomiting; 
neurologic signs may localize to cerebrum, 
brainstem, or suggest transverse myelopathy.• PH leads to hypertensive splanchnic 
vasculopathy—may provoke gastroduodenal 
bleeding/ulceration because of thin ­walled 
dilated arterials; may progress to perforation 
and septic peritonitis, life ­endangering blood 
loss if coexistent coagulopathy; can provoke 
severe HE; causes anorexia, vomiting, diarrhea, 
abdominal pain, anemia, and sometimes iron 
deficiency (if chronic blood loss).
• Urogenital—obstructive uropathy due to 
ammonium biurate urolithiasis, gross or 
microscopic hematuria, pollakiuria, dysuria, 
rare severe hematuria (ureteral APSS varices).
• Multiple tortuous vessels—represent 
acquired vasculature interconnecting portal 
and systemic venous circulations.
• Lack of valves in main portal vein 
structure allows blood to follow “a path of 
least resistance” through APSS to vena cava 
(systemic circulation). Valves in portal 
tributaries influence hepatofugal circula ­
tory routes.
• PH—results from many disease processes.
• Common causes of PH—diffuse hepatic 
fibrosis with or without cirrhosis; chronic 
unresolved EHBDO (>6 weeks); portal 
venous thromboembolism (TE), hepatic 
sinusoidal occlusion syndrome (zone 3, injury 
causing regional parenchymal collapse or 
vascular damage to hepatic venules, veins).
• Less common causes of PH involve 
idiopathic PH or NCPH (obliteration of 
tertiary portal venules), blockade of large 
hepatic veins or prehepatic vena cava (Budd–
Chiari syndrome) by thrombi, neoplasia or 
vascular “kinking”; disorders constraining 
splanchnic portal circulation: vascular 
stricture or strangulation, severe portal vein 
atresia rare congenital or acquired hepatic AV 
malformation(s) causing arterialization of the 
portal circulation, or severe intrahepatic 
portal vein atresia.
• Episodic HE.
• Ammonium urate urolithiasis.
  DIAGNOSIS
• CNS signs—infectious disorders (e.g., FIP , 
FeLV ­ or FIV ­related infections or conditions, 
canine distemper, toxoplasmosis, other); 
toxicities (e.g., lead, mushrooms, drugs, acute 
hepatic failure); hydrocephalus; idiopathic 
epilepsy; metabolic disorders (e.g., severe 
hypoglycemia, hypo ­ or hyperkalemia, 
hypocalcemia, severe hypophosphatemia).
• Gastrointestinal signs—bowel obstruction; 
dietary indiscretion; foreign body ingestion; 
• Urinary tract signs—bacterial urinary tract 
infection; urolithiasis; obstructive uropathy.• PU/PD—disorders of urine concentration 
(diabetes insipidus, diabetes mellitus, adrenal 
hyperplasia, hypercalcemia), primary PD, 
congenital or acquired renal disease.
• Causes of abdominal effusion—
cardiopulmonary disorders causing right ­
sided heart failure; pericardial disease; 
primary inflammatory hepatopathies; 
infiltrative hepatic disease (e.g., neoplasia, 
amyloid); liver lobe torsion; nonhepatic 
abdominal disorders associated with effusions 
(e.g., splenic torsion, visceral neoplasia, 
carcinomatosis, pancreatitis); or peritonitis: 
chemical (e.g., bile, urine, chyle) or septic.
• CBC—microcytosis (reflects portosystemic 
shunting or iron deficiency); mild non ­
regenerative anemia common; poikilocytes 
(cats) and target cells (dogs).
• Biochemistry—low BUN, low to low ­
normal creatinine, glucose, albumin, and 
cholesterol are common; variable liver enzyme 
activity (ALP usually high in young animals), 
ALP induction by inflammatory cytokines or 
cholestasis, ALT normal or elevated; bilirubin 
variable; features depend on underlying cause 
and chronicity.
• Urinalysis—variable urine concentration; 
ammonium biurate crystalluria, hematuria, 
pyuria, and proteinuria reflect urolithiasis or 
• Total serum bile acids (TSBA)—sensitive 
indicator of PSS; variable pre ­ with markedly 
increased post ­meal values (>100 μmol/L); 
“shunting pattern” implicated by relatively 
low pre ­ and markedly increased post ­meal 
values; however , 10–20% dogs and cats have 
higher pre ­ than post ­meal TSBA reflecting 
slow gastric or enteric transit or delayed 
gallbladder contraction.
• Blood ammonia—fasting, sensitive but 
inconsistent indicator of HE and shunting; 
ammonium biurate crystalluria infers high 
blood ammonia (evaluate 3 urine specimens, 
4–8 hours after eating); ammonia tolerance 
testing—(oral or rectal NHCl4) best test for 
ammonia intolerance; caution : may induce HE.
• Coagulation tests—prolonged PT, aPTT, 
reflect severity of liver dysfunction, synthetic 
failure, DIC, or vitamin K1 adequacy; low 
protein C activity reflects PSVA or APSS, 
enteric or renal losses or consumption.
• Abdominal effusion—usually pure or 
modified transudate.
IMAGING
• Liver size depends on underlying cause; 
microhepatia common in dogs with chronic 
liver disease with APSS, PSVA, or severe 
portal vein atresia. Some disorders associate

IMAGING
portal vein atresia. Some disorders associate 
with large liver size or large liver lobes: AV 
malformations, some DPM (cystic lesions).

1116  Blackwell’s Five-Minute Veterinary Consult  
P• Abdominal effusion—impairs visualization 
of visceral margins; ascites associated with 
severe portal atresia, some PSVA after surgical 
attenuation, some animals with DPM (CHF 
phenotype) with APSS, chronic liver disease 
with APSS, and other causes of PH.
unless radiodense mineral shell (infection).
• Size of post ­hepatic vena cava may reflect 
pericardial or cardiac causes (distended vein).
Radiographic Portovenography
Demonstrates multiple APSS; not 
recommended due to complicating risks, see 
alternatives.
• Liver size depends on underlying cause. 
May disclose change in size or absence of 
specific liver lobes or gallbladder in DPM or 
AV malformations.
• May disclose disease ­related hepatic 
parenchymal or biliary changes.
• APSS—characterized by hepatofugal portal 
flow (unreliable US detection) and APSS 
using color ­flow Doppler; tortuous APSS 
varices have turbulent blood flow; APSS often 
situated adjacent to left kidney or associated 
with splenic vasculature.
• Intrahepatic AV communication/fistula—
pulsating arterialized vascular within enlarged 
liver lobe, abdominal effusion and APSS.
• Other causes of PH and APSS are detected 
using US color ­flow Doppler: portal venous 
thrombi or stricture, hypoplastic portal vein 
at porta hepatis, diminished hepatic venule/
vein filling (venoocclusive syndrome), or 
Budd–Chiari hepatic vein outflow 
• Abdominal effusion—common.
• Uroliths—renal pelvis, urinary bladder; rare 
ureteral.
Colorectal (CRS) or Splenoportal (SPS) 
Scintigraphy
• Sensitive noninvasive test that confirms 
PSS.
• Cannot definitively differentiate PSVA 
from APSS.
• CRS—administer Tc99m pertechnetate into 
colon.
• SPS—isotope splenic injection via US 
guidance under heavy sedation or anesthesia; 
advantage in using less isotope, may miss 
caudal rectal PSVA.
Noninvasive imaging of choice; details 
vascular anatomy, visceral abnormalities.
• Hepatic aspiration—usually cannot 
differentiate disorders causing APSS.
or laparoscopic sampling best approach; 
obtain tissue from several ( n = 3) liver lobes; T ru­Cut samples may not provide adequate 
tissue for definitive diagnosis.
• Gross—small, irregularly contoured liver 
with chronic liver disease (cirrhosis, fibrosis).
• Normal to large liver in early venous outflow 
obstruction: Budd–Chiari, sinusoidal occlusion 
syndrome.
• Isolated large liver lobe—intrahepatic AV 
• Normal to small liver—DPM (CHF 
phenotype), NCPH, portal TE, portal atresia, 
PSVA.
• Normal to large liver in some cats with 
DPM.
  TREATMENT
Inpatient—severe signs of HE or tense 
abdominal effusion requiring therapeutic 
abdominocentesis and critical care.
Diet
• Nutritional support—essential to maintain 
body condition to optimize control of 
hyperammonemia ­associated HE; species ­
specific balanced, restricted ­protein diet 
(avoid red meat, organ meat, fish in dogs); 
protein allowance optimized to tolerance (see 
Hepatic Encephalopathy). Cats have different 
protein requirements compared to dogs.
• Protein allowance titrated to response 
with adjunctive treatment modulating 
production and absorption of enteric toxins 
contributing to HE (colonic products 
mainly); use commercial diets formulated 
for liver disease or moderate renal 
insufficiency as a baseline diet.
• Dogs—commercial liver diets provide 
2.2–2.5 g protein/kg body weight when fed 
to meet energy requirements; titrate protein 
using 0.25 g/kg additional allocations q5–7 
days until optimized tolerance determined: 
dairy and soy protein are best sources for 
dogs; if necessary white meat chicken can be 
introduced in small amounts to stimulate 
appetite.
• Cats—pure carnivores require meat ­derived 
protein; use diets for renal insufficiency.
• Parenteral nutrition rarely used—see 
Hepatic Encephalopathy.
• Sodium restriction important in dogs with 
ascites; 50–100 mg sodium/100 kcal or 
<0.2% dry matter basis formula of sodium; 
initiate before or with start of diuretic therapy.
• Educate client of HE and potential for 
ammonium biurate obstructive uropathy 
(males); permanent pre ­scrotal urethrostomy 
may be needed (persistent ammonium 
biurate uroliths).• Educate client how to adjust diuretics 
(as­needed basis) to mobilize abdominal 
effusion.
• Educate client how to adjust oral 
medications and use enemas (as ­needed basis) 
to ameliorate HE.
• Emphasize importance of sodium 
restriction if ascites.
• Enteric hemorrhage—associated with 
hypertensive splanchnic vasculopathy and 
coagulopathy; some clinicians use prophylac -
tic acid blockers or gastroprotectants to 
reduce risk, however, ulceration is not linked 
with hypergastrinemia; symptomatic animals 
treated with proton pump inhibitor 
(omeprazole; pantoprazole) and sucralfate; 
may require blood component therapy or 
DDAVP (see Coagulopathy of Liver Disease) 
if critical hemorrhage.
• Abdominal effusion—sequentially measure 
weight, girth (standardize measurements: 
location and operator) to monitor ascites; 
advise dietary sodium restriction combined 
with titrated dosing of furosemide with 
spironolactone.
• Conventional diuretics—combined use of 
furosemide and spironolactone is superior to 
single drugs alone; furosemide 0.5–2 mg/kg 
PO q12–24h and spironolactone 0.5–2 mg/
kg PO q12h, single loading dose of 
spironolactone (doubled dose) followed by 
dose titrations based on response q4–5 days 
with close monitoring of serum electrolytes 
and renal function. Adjustments: incremental 
25–50% dose increase. Spironolactone is 
potassium sparing and a less potent diuretic 
than furosemide. Furosemide is potassium 
wasting and typically initiates a brisk diuresis 
that can provoke RAAS response with effect 
attenuated by spironolactone.
be superior for ascites control compared to 
conventional diuretics (proven in humans, 
e.g., tolvaptan); this class of drugs is not 
routinely available or affordable for 
veterinary patients; no relevant clinical 
experience.
therapeutic abdominocentesis (see 
Hypertension, Portal). May reflect insidious 
increased sodium intake or RAAS response to 
diuresis.
• Avoid dehydration or hypokalemia by 
frequent monitoring initially: these can 
provoke HE.
due to reduced first ­pass extraction (PSS), Portosystemic Shunting, Acquired  (continued)

Canine and Feline, Seventh Edition  1117
Paltered hepatic metabolism/biotransformation, 
and reduced protein binding.
• Remain vigilant for diuretic ­induced 
dehydration and electrolyte dysregulation that 
may provoke HE and/or hepatorenal 
syndrome (acute renal failure due to severe 
vasoconstriction).
• Beware that aggressive therapeutic 
abdominocentesis may provoke hypotensive 
post­centesis syndrome (see Ascites).
Avoid metoclopramide if using spironolactone 
(blocks effect); avoid NSAIDs as these may 
inhibit furosemide ­induced diuresis, potentiate 
renal injury, or provoke sodium accumulation.
  FOLLOW-UP
• Reevaluate patient’s at ­home demeanor and 
appetite as a reflection of HE.
condition, muscle mass, weight, abdominal 
girth, CBC, serum biochemistry, and urine 
(concentration, ammonium biurate 
crystalluria); TSBA not useful for sequential 
evaluation as these are predictably increased 
with APSS and ursodeoxycholic acid (drug 
measured in assay) administration.
• Adjust medical management to alleviate 
episodic HE, ammonium biurate crystalluria, 
and abdominal effusion.
• Inspect patient carefully for evidence of 
clinical bleeding; determine need for inter­
mittent chronic vitamin K1 administration 
(parenteral route).PREVENTION/AVOIDANCE
• Early treatment of acquired liver disease 
and EHBDO minimizes fibrosis/remodeling.
• Cautious PSVA attenuation.
• T reat underlying disorder(s).
• Enteric hemorrhage associated with 
hypertensive vasculopathy; may require acute 
intensive care: manage hypovolemia, 
coagulopathy, and ensuing HE; may require 
surgical resection of involved gut (rare).
• Dehydration, contraction alkalosis, azotemia, 
acute renal failure—complications of diuretics.
• Death risk—from liver failure, HE complica ­
tions, lethal enteric hemorrhage, or sepsis.
• Varies with underlying cause.
• Management of chronic liver disease or 
hepatic fibrosis seemingly extends life.
• Animals with NCPH and DPM (CHF 
phenotype) may live >5 years if managed 
successfully during symptomatic illnesses.
• Ascites.
• Enteric bleeding/ulceration.
• Obstructive uropathy.
SEE ALSO
• Ascites.
Hepatic Fibrosis).• Hepatic Encephalopathy.
• Portal Hypertension.
syndrome.
drug.
Iwakiri Y. Pathophysiology of portal 
hypertension. Clin Liver Dis. 2014, 
18(2):281–291.
Simonetto DA, Liu M, Kamath PS. Portal 
hypertension and related complications: 
diagnosis and management. Mayo Clinic 
Proc 2019, 94:714–726.
Consulting Editor  Kate Holan(continued)  Portosystemic Shunting, Acquired

1118  Blackwell’s Five-Minute Veterinary Consult  
PPortosystemic Vascular Anomaly, Congenital
  BASICS
• Aberrant venous connections between the 
portal and systemic circulations; macroscopic 
shunts permit portal hepatofugal circulation 
(flow away from or around the liver).
• May be extrahepatic portosystemic vascular 
anomaly (E-PSVA) or intrahepatic (I-PSVA).
• Most are single vessels; occasionally two 
shunts may be identified.
• Most small-breed dogs with PSVA also have 
microscopic vascular abnormalities (see 
Hepatoportal Microvascular Dysplasia).
• Clinical signs—reflect hepatofugal 
circulation that prohibits hepatic cleansing of 
enteric toxins, food-derived nitrogenous 
toxins, and other noxious colonic substances 
from portal blood.
• Microhepatia—deprivation of splanchnic 
hepatotrophic factors (e.g., insulin) causes 
hepatic atrophy.
• Episodic hepatic encephalopathy (HE)—
associated with consumption of high-protein 
foods, gastrointestinal bleeding, other causes 
of increased heme turnover (blood transfusions, 
hemolysis), dehydration, azotemia, alkalosis, 
hypokalemia, infections, constipation, 
catabolism, and certain drugs.
• Ammonium biurate crystalluria/urolithiasis—
reflect hyperammonemia and impaired 
conversion of uric acid to water-soluble 
allantoin; may be a presenting problem.
• Severity of clinical signs reflect the 
magnitude of macroscopic shunting.
• Nervous—episodic HE in most but not all.
• Gastrointestinal—intermittent inappetence; 
vomiting; diarrhea; pica; ptyalism (cats).
• Urogenital— “plump” kidneys; ammonium 
urate urolithiasis; 50% male dogs cryptorchid 
in one retrospective report.
• Asymptomatic—up to 20% of dogs with 
PSVA.
GENETICS
• E-PSVA—most common in small-breed 
dogs (e.g., Yorkshire terrier, Cairn terrier, 
Maltese, Tibetan spaniel, miniature 
schnauzer, Norfolk terrier, pug, shih tzu, 
Havanese, papillon.
• I-PSVA—most common in large-breed dogs 
(e.g., Irish wolfhound, Labrador retriever, Old 
English sheepdog, golden retrievers).
• Autosomal dominant complex polygenic 
inheritance suspected to cause PSVA/micro -
vascular dysplasia (MVD) trait in small-breed 
dogs; MVD most common phenotype.
• I-PSVA—appears heritable in Irish 
wolfhounds patent ductus venosus type I-PSVA 
and kindred of Labrador retrievers, Old English 
sheepdogs, golden retrievers.INCIDENCE/PREVALENCE
0.2–0.6% of large referral clinic.
Species
Dog and cat; most common in small-breed 
dogs.
Higher risk—purebred and mixed small 
“terrier” type dogs; cats—domestic shorthair, 
fewer pure breeds.
• Usually identified in juveniles; some 
asymptomatic dogs as old as 13 years at initial 
• Asymptomatic animals present older; 
miniature schnauzers and dogs with porto -
azygous shunts.
N/A
SIGNS
• Stunted growth—common.
• Signs often initiate with weaning of puppy 
or kitten to commercial growth foods.
• Gastrointestinal signs—inappetence, 
vomiting, diarrhea, pica.
• Cats—ptyalism.
• Episodic HE—most dramatic and 
predominating sign in many dogs, improves 
with fluids, broad-spectrum antibiotics, and 
lactulose.
• CNS signs—weakness, propulsive circling 
or pacing, vocalization, apparent hallucinations, 
ataxia, disorientation, head pressing, signs 
consistent with transverse myelopathy, vague 
hyperpathia, amaurotic blindness, behavioral 
changes (aggression in cats), twitching or 
trembling, focal or generalized seizures, or 
progressive obtundation to coma.
• Urinary signs—polyuria/polydipsia 
(PU/PD); ammonium biurate crystalluria: 
pollakiuria, dysuria; hematuria; urethral/
ureteral ammonium biurate urolith 
• Asymptomatic—up to 20% of dogs.
• Affected bitches may produce viable 
litters.
• Normal appearance, but most have stunted 
stature; microhepatia; HE; copper-colored 
irises in non-blue-eyed cats (note: Persian, 
Russian blue, some others normally have 
copper-colored iris; iris color does not change 
with PSVA ligation).
CAUSES
Congenital developmental vascular 
malformations.  DIAGNOSIS
• CNS signs—infectious disorders (FIP-, 
FeLV- or FIV-related infections in cats, canine 
distemper, toxoplasmosis); toxicities (lead, 
mushrooms, recreational drugs); congenital CNS 
malformations (hydrocephalus); congenital 
storage disorders; idiopathic epilepsy; metabolic 
hyperkalemia, hypocalcemia); necrotizing 
meningoencephalitis or granulomatous 
meningoencephalitis—idiopathic inflammatory 
CNS syndromes in small-breed dogs (e.g., pug, 
Maltese, Yorkshire terriers).
infection or other forms of urolithiasis.
• PU/PD—disorders of urine concentration 
(diabetes insipidus, diabetes mellitus, 
abnormal adrenal function, hypercalcemia), 
primary polydipsia.
• MVD—in asymptomatic PSVA animals.
• CBC—microcytosis; mild non-regenerative 
anemia; poikilocytosis (cats); target cells (dogs).
• Biochemistry—inconsistent low BUN, 
creatinine, cholesterol; hypoglycemia—in 
young tiny toy breeds, variable liver enzyme 
activity (ALP high in young patients), ALT 
normal or elevated; bilirubin normal; 
hypoalbuminemia inconsistent and mild.
• Urinalysis—normally concentrated or 
dilute urine; ammonium biurate crystalluria; 
hematuria, pyuria, and proteinuria: with 
urolithiasis or infection.
• Total serum bile acid (TSBA)—sensitive 
indicator of portosystemic shunting (PSS); 
random fasting values may be within 
reference intervals; 2 hours post-meal values 
usually markedly high (>100 μmol/L); always 
use paired samples around confirmed meal 
ingestion; no need to fast before testing. 
TSBA often remain abnormal in small-breed 
dogs after PSVA attenuation due to 
concurrent MVD. Important TSBA testing 
strategy—food-initiated enterohepatic bile 
acid challenge essential; verify meal 
consumption; feed typical size meal; feed 
dog’s regular diet for testing.
ammonia tolerance testing—oral or rectal 
NHCl4 administration; may cause transient HE.
• Coagulation tests—prolonged clotting 
times compared to healthy dogs but not 
clinically significant; are not associated with 
increased risk for bleeding.

Canine and Feline, Seventh Edition  1119
P• Protein C—low values help differentiate PSVA 
from MVD; usually <70% in symptomatic 
PSVA, usually >70% in MVD, may be ≥70% in 
asymptomatic PSVA. Test reflects magnitude of 
macroscopic shunting. Protein C especially 
useful for postoperative assessment after PSVA 
ligation if initial activity subnormal; normali -
zation coordinates with good surgical outcome 
despite sustained high TSBA values. Protein C is 
not similarly applicable in cats.
IMAGING
• Microhepatia—dogs > cats.
• Renomegaly—some dogs.
• Ammonium urate urolithiasis—radiolucent 
unless combined with radiodense mineral shell.
• Mesenteric portography—old gold standard 
for PSVA diagnosis.
• Currently used as intraoperative assessment 
of hepatic portal perfusion via fluoroscopy, 
accurate PSVA localization and assesses 
postligation liver perfusion.
• Subjective assessment of microhepatia and 
vascular profiles; difficult to identify some 
PSVA (portoazygos, splenophrenic, gastro -
phrenic); US identification of PSVA is highly 
• Color-flow Doppler—assists in US PSVA 
verification.
• I-PSVA—usually more easily imaged with 
US than E-PSVA.
• Other US features—renomegaly, uroliths: 
bladder, renal pelvis, rare ureteral.
• US microbubble study—can confirm PSS; 
splenic injection of agitated heparinized 
blood (microbubbles).
• Tc99m pertechnetate CRS or SPS measures 
shunt fraction; normal dog shunt fraction 
≤15%; PSVA shunt fraction usually >60% 
but depends on severity of macroscopic 
shunting; shunt fraction in MVD is usually 
mildly increased above normal.
• CRS—sensitive noninvasive test confirming 
macroscopic shunting; cannot differentiate 
PSVA from acquired PSS (APSS) or E-PSVA 
from I-PSVA.
• SPS—may miss caudal PSVA; details 
insufficient to differentiate type of shunt 
(APSS vs. PSVA or I-PSVA, E-PSVA).
Gold standard imaging modality defining 
arterial and venous circulations; definitively 
demonstrates PSVA and APSS.
• Vascular imaging provides definitive 
diagnosis of PSVA.
diagnose PSVA or MVD.• Liver biopsy—required for definitive 
diagnosis of portal venous hypoperfusion; rules 
out most acquired hepatobiliary disorders 
causing increased TSBA except splanchnic 
portal thromboembolism (TE), noncirrhotic 
portal hypertension (NCPH) and cannot 
usually differentiate MVD from PSVA.
• Open surgical wedge or laparoscopic liver 
biopsies preferred with samples collected from 
several ( n = 3) liver lobes; avoid sampling 
caudate lobe.
• Needle core samples may be inadequate for 
definitive diagnosis of portal venous hypo- 
 perfusion.
• Gross—small, smooth-surfaced liver; PSVA 
may be difficult to verify at autopsy due to 
collapse of portal vasculature.
• Histologic features—cannot discriminate 
MVD, PSVA, NCPH, or extrahepatic portal 
venous TE/occlusion without history, clinical 
findings, and imaging details. Note: dogs 
with MVD lacking PSVA have histologic 
features identical to PSVA but lack macro -
scopic shunting.
• Portal venous hypoplasia—invalid 
histologic diagnosis as failure to identify 
perfused portal veins can reflect any cause of 
portal venous hypoperfusion.
• Note: dogs ≤4 months of age demonstrate 
  TREATMENT
Inpatient—severe signs of HE; medical 
intervention prior to liver biopsy and PSVA 
ligation.
See Hepatic Encephalopathy.
DIET
body condition and muscle mass.
• Species-specific balanced protein-restricted 
diet—use commercial canine liver diet for 
dogs and feline renal diet for cats as a baseline 
diet. To these diets, additional protein 
allocations are titrated based on patient 
response, in combination with treatments 
ameliorating HE.
• Dogs—as tolerated, add an additional 
0.25 g up to 1.0 g protein/kg body weight 
using dairy quality protein (e.g., cottage 
cheese, cheddar cheese, yogurt, scrambled 
eggs); incrementally adjust observing over 
5–7 day intervals (see Hepatic Encephalo-  
pathy).
• Cats—as tolerated, additional white meat 
chicken may be used.
• Avoid organ meats, fish, and red meat as 
protein sources.• Asymptomatic or minimally symptomatic 
animals can survive well with dietary and 
medical interventions.
• Explain therapeutic options: medical vs. 
surgical and risks of each managerial strategy.
• Surgical ligation—has potential to cure; 
expect improvement in all symptomatic dogs 
that tolerate some degree of shunt attenuation.
• Postoperative clinical signs—may persist 
despite PSVA attenuation requiring chronic 
nutritional and medical management; some 
dogs can have medical and dietary inter -
ventions withdrawn.
• Clinical improvement may occur after 
surgical ligation despite persistent high TSBA 
values.
• Surgical/anesthetic risks—influenced by 
surgeon skill and experience, hospital, 
supportive critical care, type of PSVA, and 
histologic liver features.
• Monitoring protein C—can document 
improved portal perfusion in dogs with 
sustained high TSBA values; protein C 
activity will increase and may normalize with 
successful surgery (if low preoperatively); 
retest 2–6 months after surgery. This test is 
useful in cats for this purpose.
• If surgery not pursued or ligation not 
tolerated: remain vigilant for ammonium 
biurate obstructive uropathy; urethral 
obstruction (males) may require permanent 
urethrostomy.
• HE—should be mitigated with medical 
management before anesthesia and surgery.
• ICU monitoring—recommended post -
operatively for 72–96 hours.
• Surgical PSVA ligation—optimal goal of 
complete ligation; may not be tolerated 
leading to APSS. APSS may develop with any 
method of shunt attenuation: direct silk 
ligation, ameroid device, cellophane banding, 
or IV coiling (I-PSVA).
• Partial PSVA ligation—improves patient 
health in most cases.
• Degree of tolerated PSVA closure judged at 
surgery—physiologic responses to temporary 
shunt occlusion but intraoperative assessments 
can still be inaccurate or misleading.
• Intraoperative portography advised—
verifies correct PSVA identification and 
evaluates immediate change in hepatic portal 
perfusion as a real-time assessment.
• Ameroid constrictor, cellophane banding, 
IV coiling—gradual PSVA attenuation, 
reduce immediate postoperative surgical risk; 
caution : may later result in APSS in some 
patients, degree of PSVA attenuation is 
unknown with these methods without 
follow-up vascular imaging.
• Intrahepatic PSVA—more difficult to ligate 
than E-PSVA; right-sided I-PSVA most 
difficult, left-sided I-PSVA consistent with (continued)  Portosystemic Vascular Anomaly, Congenital

1120  Blackwell’s Five-Minute Veterinary Consult  
Ppatent DV easiest; IV coiling an alternative 
method but may require multiple procedures 
for optimal response, is expensive, requires 
interventional training.
• Ammonium biurate urolith removal—
bladder stones most common, ensure urethra 
is free of uroliths by retrograde catheterization/
flushing.
• Occasional male dog may require 
permanent urethrostomy.
Postoperative Complications
• Prolonged postoperative recovery—small 
patients developing intraoperative 
• Acute severe PH—may reflect intolerance 
to PSVA ligation, flipping of ameroid 
constrictor, portal vein thrombi; mesenteric 
ischemia characterized by acute enteric 
hemorrhage, abdominal pain, tachycardia, 
hyper- or hypothermia, pancreatitis, 
endotoxemia, sepsis, acute renal failure and 
hypovolemic shock.
• Seizures—usually develop within 96 hours 
of PSVA ligation; risk factors remain 
unclarified with no demonstrated association 
with presence or absence of preoperative 
seizures, type of PSVA, method or degree of 
shunt attenuation, or patient age. 
Postoperative seizure prevalence—recent large 
multihospital study of dogs with seizures 
within 7 days of surgery: 6.7% of 524 dogs 
without preoperative levetiracetam treatment 
and 8.3–11.2% of 416 dogs receiving 
different pre- and postoperative levetiracetam 
protocols. One study implicates greater risk 
for pugs. Postoperative seizures reported in 
~22% of cats undergoing PSVA ligation.
• Management of postligation seizures—often 
unsuccessful with persistent neurologic deficits 
in survivors, especially cats. T reatment remains 
anecdotal and requires consideration of 
cerebral edema if protracted seizure activity 
and intensive supportive care; successful 
management protocols (dogs and cats) 
include: IM phenobarbital (4–6 mg/kg IM 
q12h) combined with propofol CRI (0.3–0.6 
mg/kg/minute titrated to achieve heavy 
sedation to drug-induced coma), and in one 
dog additional medetomidine (CRI (0.016 
μg/kg/min). Initial treatment with IV 
levetiracetam has variable short-term response; 
flumazenil has no effect. Follow-up at-home 
treatments with phenobarbital, KBr, and/or 
levetiracetam have been successfully used.
• Abdominal effusion—typically transient 
after shunt ligation resolving within 7 days; 
alone, does not indicate intolerable PSVA 
attenuation; serious PH indicated by signs 
of mesenteric ischemia; monitor girth and 
body weight postoperatively to evaluate 
effusion.
• Administration of hetastarch can increase 
perioperative bleeding.
• Blood component therapy containing acid 
citrate dextrose may provoke hypocalcemia and coagulopathy (hypercitratemia) in 
patients <5 kg.
• Emergency surgery—rarely required for 
ligature removal after PSVA attenuation; 
ameroid constrictors difficult to impossible to 
remove; IV coils nonretrievable.
See Hepatic Encephalopathy and previous 
description of postoperative seizure 
Remain aware of altered drug metabolism 
related to reduced first-pass extraction, altered 
hepatic metabolism/biotransformation.
  FOLLOW-UP
• Reevaluate—at-home behavior, cognitive 
function, water consumption, body 
condition, weight, girth circumference; CBC 
for resolution of microcytosis, biochemistry 
for normalization of cholesterol, BUN, 
creatinine, urinalysis for resolution of 
• TSBA (small-breed dogs)—persistent high 
values do not substantiate surgical failure 
because of common coexistent MVD.
• If low preoperative protein C (<70%), 
reevaluate 2–4 months after surgery as 
evidence of improved liver perfusion—values 
will improve or normalize.
Multiple APSS—should be detected 
preoperatively by US imaging; if identified 
these indicate need for liver biopsy, 
contraindicate shunt ligation, and implicate 
severe portal atresia or another underlying 
disorder causing PH; PSVA is not associated 
with PH and APSS.
• Cannot predict individual response to 
surgery but asymptomatic dogs with 
preoperative normal protein C activity have 
the best prognosis for curative ligation.
• Dogs—ligation improves signs in ∼80% 
symptomatic patients.
• Cats—increased risk for development of 
APSS with full ligation.
• Post-surgery—continue HE management 
(especially diet) until reevaluation and 
observations confirm improvements.
• Some patients—require indefinite nutritional 
and medical support after surgical ligation.• Partial ligation—may result achieve full 
shunt attenuation by granulation response to 
ligature.
• Ameroid constrictor—may result in full 
ligation within hours or a few days, may cause 
APSS; rare erosion of portal vein causes 
catastrophic hemorrhage.
• Cellophane banding—some procedures fail 
because wrong type of cellophane used.
• Increased risk for poor surgical outcome—
small dogs with zone 3 lipogranulomas 
shrouding hepatic venules; cats generally have 
less predictable surgical outcome compared to 
dogs.
• Despite initial good response, 
recrudescent shunting may develop 3 years 
post ligation.
• Asymptomatic nonligated PSVA dogs can 
have normal life expectancy with optimized 
• Copper-colored iris (cats).
• Cryptorchidism (dogs).
• Surgical outcome may be good in young 
and old patients, especially those with 
minimal signs of HE (asymptomatic).
• Dogs with PSVA identified at older ages are 
usually asymptomatic for HE and may have 
easily attenuated shunts (portoazygous, 
splenophrenic, or gastrophrenic).
• Asymptomatic bitches can carry viable 
litters to term.
• Asymptomatic dogs have been naively used 
for stud.
• Breeding PSVA dogs not advised (genetic 
disorder, especially small-breed dogs).
SYNONYMS
Portacaval shunt.
SEE ALSO
• Hepatoportal Microvascular Dysplasia.
• DV = ductus venosus.
• E-PSVA = extrahepatic PSVA.
• I-PSVA = intrahepatic PSVA.
• NCPH= noncirrhotic portal hypertension.Portosystemic Vascular Anomaly, Congenital  (continued)

Canine and Feline, Seventh Edition  1121
P• PH = portal hypertension.
• PSS = portosystemic shunting.
Heidenreich DC, Giordano P , Kirby BM. 
Successful treatment of refractory seizures 
with phenobarbital, propofol, and 
medetomidine following congenital 
portosystemic shunt ligation in a dog. J Vet 
Emerg Crit Care (San Antonio) 2016, 
26:831–836.
Lipsomb VJ, Jones HJ, Brockman DJ. 
Complications and long-term outcomes of the ligation of congenital portosystemic 
shunts in 49 cats. Vet Rec 2007, 
160:465–470.
Fukushima K, Kanemoto H, Ohno K, et al. 
Computed tomographic morphology and 
clinical features of extrahepatic 
portosystemic shunts in 172 dogs in Japan. 
Vet J 2014, 199:376–381.
Mehl ML, Kyles AE, Hardie EM, et al. 
Evaluation of ameroid ring constrictors for 
treatment for single extrahepatic 
portosystemic shunts in dogs: 168 cases 
(1995–2001). J Am Vet Med Assoc 2005, 
226:2020–2030.
Mullins RA, Sanchez Villamil C, de Rooster 
H, et al. Effect of prophylactic treatment with levetiracetam on the incidence of 
postattenuation seizures in dogs undergoing 
surgical management of single congenital 
extrahepatic portosystemic shunts. Vet Surg. 
2019, 48:164–172.
Weisse C, Berent AC, Todd K, et al. 
Endovascular evaluation and treatment of 
intrahepatic portosystemic shunts in dogs: 
100 cases (2001–2011). J Am Vet Med 
Assoc 2014, 244:78–94.
available online(continued)  Portosystemic Vascular Anomaly, Congenital

1122  Blackwell’s Five-Minute Veterinary Consult  
PPoxvirus Infection—Cats
  BASICS
OVERVIEW
• Member of the genus Orthopoxvirus , family 
Poxviridae.
• Enveloped, double-stranded DNA virus, 
resistant to drying (viable for years) but 
readily inactivated by most disinfectants.
• Geographically limited to Eurasia.
• Relatively common.
• Serologic evidence of infection may 
approach 10% in cats in western Europe.
• Cats—domestic and exotic.
• No age, sex, or breed predisposition.
SIGNS
• Skin lesions—multiple, circular; dominant 
feature; usually develop on head, neck, or 
• Primary lesions—crusted papules, plaques, 
nodules, crateriform ulcers, or areas of 
cellulitis or abscesses.
• Secondary lesions—erythematous nodules 
that ulcerate and crust; often widespread; 
develop after 1–3 weeks.
• Oral lesions—erosions, ulcers either 
concurrently or alone (20% of cases).
• Pruritus variable.
• Systemic—20% of cases; anorexia, 
lethargy, pyrexia, vomiting, diarrhea, 
oculonasal discharge, conjunctivitis, 
• Reservoir host—wild rodents (voles, mice, 
gerbils, ground squirrels).
• Infection in cat thought to be acquired 
during hunting and being wounded by 
infected rodents; most common in young 
adults and active hunters, often from rural 
• Lesions—often develop at the site of a bite 
wound (presumably inflicted by the prey 
animal carrying the virus).
• Most cases occur between August 
and October, when small wild mammals 
are at maximum population and most 
active.
• Severe cutaneous and systemic signs with 
poor prognosis are frequently associated with 
immunosuppression (iatrogenic or 
coinfection with feline leukemia virus or 
feline immunodeficiency virus).
• Cat-to-cat transmission—rare; causes only 
subclinical infection.
  DIAGNOSIS
• Bacterial and fungal infections.
• Eosinophilic granuloma complex.• Neoplasia—particularly mast cell tumor; 
lymphoma.
• Miliary dermatitis.
Noncontributory.
Serologic testing—demonstrate rising titers; 
hemagglutination inhibition, virus neutralizing, 
complement fixation, or ELISA; titers may 
remain high for months or years.
• Virus isolation from scab material—
definitive diagnosis; 90% positive.
• Electron microscopy of extracts of scab, 
biopsy, or exudate—rapid presumptive 
diagnosis; 70% positive.
• Skin biopsy—characteristic histologic 
changes of epidermal hyperplasia and 
hypertrophy, multilocular vesicle and 
ulceration, large eosinophilic intracytoplasmic 
inclusion bodies, immunofluorescence tests.
• PCR.
• Serologic assays: immunofluorescent 
antibody, ELISA, and virus neutralization 
assays.
  TREATMENT
• No specific treatment.
• Clean and treat ulcerated areas to prevent 
secondary infection.
• Supportive (antibiotics, fluids) when 
• Elizabethan collar—to prevent self-induced 
damage.
Antibiotics—prevent secondary infections.
Immunosuppressive agents (e.g., glucocorti -
coids, megestrol acetate)—absolutely 
contraindicated because they can induce fatal 
  FOLLOW-UP
• Natural reservoir hosts are probably small 
rodents, with cats infected incidentally; 
therefore, housing cats indoors should help 
prevent infection in cats.
• Vaccines—none available; vaccinia virus 
may be considered for valuable zoo 
collections, but its effects in nondomestic cats 
have not been investigated.EXPECTED COURSE AND PROGNOSIS
• Most cats recover spontaneously in 1–2 
months.
• Healing may be delayed by secondary 
bacterial skin infection.
• Prognosis is poor with severe respiratory or 
pulmonary involvement.
• Rare human poxvirus infections have been 
linked to contact with infected cats with skin 
lesions; use basic hygiene precautions 
(disposable gloves) when handling infected cats.
• Infection is usually mild and transient in 
healthy humans, but severe and even lethal 
infections can occur in immunocompromised 
• May cause painful skin lesions and severe 
systemic illness, particularly in the very young 
or elderly, people with a preexisting skin 
condition, and the immunodeficient.
• With discontinuation of vaccination against 
smallpox (with its cross-reactive immune 
effect) may expect increase in human poxvirus 
• Virus is hardy, can survive in scabs for 
weeks to months in environment where it can 
be source for human infection.
www.abcdcatsvets.org/cowpox-virus-infection
Bennett M. Feline poxvirus infections. In: 
Sykes JE, ed. Canine and Feline Infectious 
Diseases. St. Louis, MO: Elsevier, 2014, 
pp. 252–255.
Breheny CR, Fox V, Tamborini A, et al. Novel 
characteristics identified in two cases of 
feline cowpox virus infection. JFMS Open 
Rep 2017, 3:1–5.

Canine and Feline, Seventh Edition  1123
PPregnancy Edema in the Bitch
  BASICS
• Edema associated with pregnancy varies 
from mild to severe pitting edema of the 
distal pelvic limbs, the ventral abdomen, 
mammary glands, and perineal subcutaneous 
tissues; sometimes accompanied with an 
increase in intrauterine amniotic/allantoic 
• Abnormal fluid accumulation in the fetus/
neonate, hydrops fetalis, is a separate disorder, 
and not a comorbidity.
• Edema in canine pregnancy has been 
referred to as “hydrops” by breeders; there is 
no evidence that the condition is comparable 
to hydrops in humans. The pathophysiology 
of the pregnancy edema syndrome in the dog 
has not yet been established. Hydrops 
allantois and hydrops amnii have been 
reported in mares and cows.
• Edema can occur secondary to venous/
lymphatic compression from an enlarged, 
gravid uterus.
• In humans, pregnancy edema can be 
normal (80%), or can be associated with 
preeclampsia, pregnancy toxemia, and 
eclampsia (proteinuric hypertension); a 
placental trigger is suspected (immunologic).
• During normal pregnancy total body water 
increases both extracellularly and interstitially. 
There is also cumulative retention of sodium 
distributed between the maternal extracellular 
compartments and the fetus. Changes in 
factors governing renal sodium and water 
handling accompany alterations in local 
Starling forces whereby there is a moderate fall 
in interstitial fluid colloid osmotic pressure and 
a rise in capillary hydrostatic pressure, as well 
as changes in hydration of connective tissue.
GENETICS
Heritability unknown, breed tendencies (see 
Signalment) support DNA sampling in 
confirmed cases for future genetic evaluation.
Uncommon
N/A
Pregnancy edema occurs most commonly in 
bitches with very large litters in mid to late 
gestation. Many breeds have been affected, most commonly reported are golden 
retrievers, Labrador retrievers, pugs, 
Doberman pinschers, English bulldogs and 
French bulldogs, and bullmastiffs.
SIGNS
• Swelling/pitting edema of pelvic limbs, paws, 
mammary glands, perineum, ventrum, vulva.
• Marked abdominomegaly.
• Marked and sudden weight gain.
• Variable anorexia, nausea and lethargy; 
sometimes hemorrhagic gastroenterocolitis.
• Possible systemic hypertension.
• Possible increased allantoic/amniotic fluid 
volume.
• Possible ascites.
CAUSES
N/A
• Large litter (10–12+).
• Occurs variably with previous/subsequent 
  DIAGNOSIS
• Uteromegaly—closed pyometra, pregnancy.
• Edema—cardiogenic, secondary to 
electrolyte abnormalities, hypoalbuminemia, 
vasculitis, protein losing nephropathy or 
enteropathy, thrombosis, or hepatopathy.
• Abdominomegaly—ascites, hepato/
splenomegaly, ruptured uterus, uterine torsion.
• Hypertension—primary, secondary to renal 
disease, endocrine disease.
• May be normal; anticipated anemia of 
pregnancy, stress leukogram, possible electrolyte 
abnormalities (e.g., hyponatremia, hyperkalemia, 
hypomagnesemia). Proteinuria possible.
• Hypomagnesemia is associated with 
preeclampsia in women.
• Consider urine electrolyte evaluation if 
electrolyte abnormalities exist.
• Urine protein creatinine ratio if proteinuric.
• Adrenocorticotropic hormone stimulation 
test can identify hypo- or hyperadrenocorticism.
IMAGING
• Abdominal ultrasound with attention to 
fetal viability, and intra-abdominal, intrauterine, 
placental, allantoic and amniotic fluid 
volumes.
• Echocardiography for evaluation of dam for 
cardiac disorders.
• Blood pressure measurement, serial if 
hypertensive.
• Tocodynamometry to assess myometrial 
activity/irritability.• Fetal heart rate determinations with Doppler 
or ultrasound to determine fetal wellbeing.
• Poorly characterized; collection of deceased 
fetuses, placentae encouraged for histopatho -
• Consider uterine/placental biopsy during 
cesarean section.
• Complete necropsy with histopathology 
desirable in the event of maternal death to 
elucidate the cause.
  TREATMENT
• Address life-threatening conditions 
(malignant hypertension, hypomagnesemia) 
first, then secondary conditions (edema, 
nausea).
• Medical pregnancy termination not advised 
due to the fragile condition of the bitch and 
likely myometrial hypocontractility.
Mild distal limb edema can benefit from mild 
walking, hydrotherapy, or massage. Elevating 
the limbs and avoiding further compression 
of the caudal abdominal veins/lymphatics can 
help disseminate edema.
ACTIVITY
Appropriate but not excessive restriction.
DIET
• Mild sodium restriction if advanced heart 
disease is present.
• Appropriate-for-pregnancy dietary protein, 
especially if hypoalbuminemia or significant 
proteinuria present.
Anticipate the likely need for cesarean section 
due to litter size, uterine wall distension, and 
vulvar edema contributing to an obstructive 
dystocia.
Elective cesarean section at term, or pregnancy 
termination via ovariohysterectomy should be 
considered in cases of severe edema.
• Hypertension—hydralazine 0.5–2 mg/kg 
PO q12h, titrate up to effect; or 0.2 mg/kg 
IM; repeat q2h as needed; monitor for 
hypotension, hospitalize until normotensive. 
Continue blood pressure monitoring until 
normotension is maintained.
• Hypomagnesemia and related signs—
magnesium sulfate 0.7–1 mEq/kg/ day IV 
CRI; 0.25 mEq/kg slow IV bolus (loading 
dose); reduce 50% if patient is azotemic.

1124  Blackwell’s Five-Minute Veterinary Consult  
P• Edema—medical treatment of edematous 
conditions in pregnancy in the bitch is 
controversial and without evidence-based 
data. In human medicine, diuretics are not 
advised to treat physiologic edema of 
pregnancy and do not prevent preeclampsia.
• Nausea/anorexia—metoclopramide 
(0.1–0.2 mg/kg SC or PO q12h, ondansetron 
[FDA pregnancy category B; 0.5–1 mg/kg 
PO q8–12h], maropitant [1 mg/kg SC or 
2 mg/kg PO q 24h × 5d.] Note: safe use of 
maropitant in pregnant dogs has not been 
evaluated.)
Furosemide can cause a significant decrease in 
placental intervillous blood flow. Diuretics are 
contraindicated with contracted IV volume. 
Caution must be exercised if diuretic therapy 
is implemented.
• Any drug used is likely to cross the 
placenta; fetal effects should be considered 
and informed consent acquired.
• The use of diuretics can exacerbate hyper -
tension by promoting dehydration, and at this 
time, use of diuretics cannot be routinely 
recommended unless studies demonstrate 
benefit to the dam/fetuses (beyond anecdotal 
reports).
• In humans, the role of diuretics in obstetric 
practice is restricted to the management of 
pulmonary edema in preeclampsia.
N/AALTERNATIVE DRUGS
Anecdotal use of the aldosterone antagonist 
spironolactone (1–2 mg/kg PO q12h) or 
furosemide (1–2 mg/kg PO q12h) has occurred 
in veterinary practice. The effects of these drugs 
on the fetuses are unknown (spironolactone is 
an antiandrogen and can feminize male rats) 
and their use is not recommended.
  FOLLOW-UP
• Dystocia secondary to uterine inertia 
related to stretching of the uterine wall.
• Fetal and maternal mortality.
Fair to guarded prognosis.
N/A
N/A
N/A
• Consider pedigree evaluation. If an 
increased incidence occurs in related bitches, 
removal from the breeding program should be 
strongly considered.• Research litter size associated with various 
stud dogs/brood bitches; select away from 
large litter size (>8).
SYNONYMS
None, as they syndrome is not well defined; 
hydrops (allantois, amnion) has been 
suggested but not documented to be the 
equivalent disease in humans and dogs.
SEE ALSO
Davidson AP . Clinical approach to abnormal 
pregnancy. In: England G, ed., BSAVA 
Manual of Canine and Feline 
Reproduction, 13-1. Quedgeley, Glos: 
BSAVA, 2012.
Davidson AP . Clinical conditions in the bitch 
and queen. In: Nelson R, Couto C, ed., 
Small Animal Internal Medicine, 6th ed. St. 
Louis, MO: Elsevier, 2019, pp. 953–990.
Davison JM. Edema in pregnancy. Kidney Int 
Supp 1997, 59:90–96.
Root Kustritz, M. Pregnancy diagnosis and 
abnormalities in the pregnant dog. 
Theriogenology 2005, 64:755–765.
Weiner CP , Buhimschi C. Drugs for Pregnant 
and Lactating Women. Philadelphia, PA: 
Churchill Livingstone, 2004.
Author  Autumn P . Davidson
Consulting Editor  Erin E. RuncanPregnancy Edema in the Bitch  (continued)

Canine and Feline, Seventh Edition  1125
PPregnancy Toxemia
  BASICS
OVERVIEW
Pregnancy toxemia is a rare condition in the 
bitch associated with an insufficient supply of 
carbohydrates to meet the increased energy 
demands of the late-gestational fetus. 
Sustained anorexia or carbohydrate-deficient 
diets result in a relative hypoglycemia and a 
negative energy balance. Prolonged negative 
energy balance causes hepatic lipolysis and 
the production of ketone bodies. Hypo -
glycemia and ketonemia are seen in bitches 
with pregnancy toxemia.
• Nervous.
Pregnant bitches, of any breed, typically late 
in gestation.
SIGNS
• Lethargy/malaise.
• Ataxia.
• Seizure.
• Coma.
• Large litters.
• Any event inciting sustained anorexia.
• Carbohydrate-deficient diets.
  DIAGNOSIS
• Puerperal tetany (hypocalcemia).
• Gestational diabetes.
• Ketonuria (no glucosuria) or ketonemia.
• Elevations in hepatocellular enzyme 
Venous blood gas analysis: metabolic acidosis.
IMAGING
Abdominal ultrasonography of the bitch to 
assess fetal viability and fetal stability. Fetal 
stress is associated with fetal heart rate <160.DIAGNOSTIC PROCEDURES
N/A
  TREATMENT
• Mildly affected (alert and appetent)—may 
resolve with appropriate carbohydrate intake; 
feed an energy-dense diet ad libitum.
• Moderately affected (clinically ill)—
dextrose IV (0.5 g/kg IV bolus, may also be 
added to isotonic crystalloid fluids to a total 
concentration of 2.5% or 5% dextrose, and 
administer as constant IV infusion); tailor 
therapy to maintain euglycemia and prevent 
swings in blood glucose; taper treatment 
slowly as patient oral intake increases.
• Severely affected (nonresponsive to above 
therapy)—termination of pregnancy or 
Concurrent hepatic lipidosis may decrease 
hepatic metabolism of certain drugs. Choose 
analgesics and anesthetics with caution.
  FOLLOW-UP
• Serial blood glucose concentration 
monitoring (q2–4h); adjust therapy as 
• Serial urine or serum ketone measurements.
• Response to treatment (increased 
carbohydrate intake, euglycemia, and 
resolving ketonuria).
Feeding an energy-dense diet during 
Fetal mortality.
Prognostic outcome depends on severity 
and response to treatment. If clinical signs 
are mild, the prognosis is good for dam and 
pups. Increased carbohydrate intake, alert 
mentation, and resolving ketonuria are 
good prognostic indicators in the dam. 
However, prolonged negative energy 
balance and ketonuria increase chances of 
fetal mortality. In severe cases pregnancy 
toxemia can be life-threatening for the dam 
and pups.  MISCELLANEOUS
N/A
N/A
• Incidence of recurrence, effects on fertility, 
and heritability not investigated.
• If underlying cause of pregnancy toxemia is 
identified and correctable (i.e., poor 
nutrition), bitch could theoretically be used 
for breeding in the future.
SEE ALSO
70:1418–1423.
Canine pregnancy. In: Canine and Feline 
Theriogenology. Philadelphia, PA: W.B. 
Saunders, 2001, pp. 66–104.
Authors  Samantha B. Souther and Victor J. 
Stora

1126  Blackwell’s Five-Minute Veterinary Consult  
P
Premature Labor
  BASICS
OVERVIEW
Inappropriate myometrial activity preterm, 
which can lead to loss of pregnancy.
Gravid female dog or cat; no age or breed 
SIGNS
• Early—often no signs, fetal resorption 
evident ultrasonographically.
• Late—vulvar discharge: hemorrhagic or 
lochia, abortion.
• History of unexplained loss of pregnancy.
• Often idiopathic; genetics can play a role. 
Secondary luteolysis results without 
• Myometrial activity inappropriate for stage 
of pregnancy precedes luteolysis.
• Primary luteal insufficiency has not been 
documented.
  DIAGNOSIS
• Term gestation, onset of normal labor.
• Pathologic loss of pregnancy (see 
Miscellaneous).
• Anemia of pregnancy can be present, and 
rarely signs of hemorrhage.
Serum progesterone: will be <2 ng/mL when 
resorption/abortion occurs.
IMAGING
• Ultrasonographic evaluation of fetal heart 
rate (stress evidenced by heart rates 
consistently <170 bpm).
• Abnormal morphologic appearance of 
fetuses in uterus following death (see Web 
Figures 1 and 2).
• Tocodynamometry is diagnostic—finding 
>0–2 contractions/hour is not normal for 
preterm (earlier than 8th week) gestation.
• Progesterone measurement with a 
quantitative (chemiluminescence, 
fluorescence enzyme immunoassay) 
progesterone assay or accurate in house 
equipment should be performed to detect 
levels <2.0 ng/mL.  TREATMENT
• In humans, bed and pelvic rest and 
antibiotics do not contribute to a positive 
outcome, although frequently prescribed.
• Tocolytic agents are advised in veterinary 
cases (beta-agonists, calcium channel 
blockers, magnesium sulfate, prostaglandin 
synthetase inhibitors).
• Tocolytics (terbutaline 0.03 mg/kg PO 
q6–12h PRN); the dose is titrated based on 
uterine monitoring.
• Progestogens compounds—progesterone in 
oil (2 mg/kg IM q72h); altrenogest (Regu-
Mate), a synthetic progestogen (0.088 mg/kg 
PO q24h); oral progesterone (Prometrium®; 
10 mg/kg PO q24h) with monitoring of 
serum progesterone q24–48h for dosage 
adjustments. Clients should be informed of 
probable side effects with exogenous 
progesterone; it should only be used if the 
serum progesterone is <2 ng/mL and 
tocolytics have failed.
• Systemic antibiotics are rarely indicated.
• Prolonged gestation if terbutaline or 
progestogen compounds are not withdrawn 
24–48 hours before due date calculated from 
first progesterone rise, luteinizing hormone 
peak, or day 1 cytologic diestrus (see Breeding, 
Timing) if natural whelping is planned. Many 
successfully managed cases have ineffective 
labor despite drug discontinuation. If elective 
cesarean section is planned, medications can 
be continued until day of surgery.
• Poor lactation if progestogen compounds 
are used (inhibits normal prolactin elevation 
resulting from declining progesterone level).
• Masculinization of female fetuses if 
progestogen compounds are used, resulting in 
infertility and genitourinary abnormalities.
• Forced retention of a pathologic pregnancy 
if idiopathic premature labor is misdiagnosed.
  FOLLOW-UP
• Serial abdominal ultrasound and/or fetal 
heart rate monitoring with Doppler to 
evaluate fetal viability.
• Serial tocodynamometry evaluating 
effective tocolysis.  MISCELLANEOUS
Usually a retrospective diagnosis by exclusion 
of all other causes of late-term abortion (see 
Abortion, Spontaneous) prompting midterm 
proactive tocodynamometry at the next 
http://whelpwise.com/
Davidson AP . Tocodynamometry detects 
preterm labor in the bitch prior to 
luteolysis. Top Companion Anim Med 
2015, 30(1):2–4.
Johnson CA. High-risk pregnancy and 
hypoluteoidism in the bitch. 
Theriogenology 2008, 70:1424–1430.
Root Kustritz MV. Use of supplemental 
progesterone in management of canine 
pregnancy. In: Concannon PW, England G, 
Verstegen III J, Linde-Forsberg C, eds., 
Recent Advances in Small Animal 
Reproduction. Ithaca NY: International 
Veterinary Information Service, 2001.
Scott-Moncrieff JC, Nelson RW, Bill RL, 
et al. Serum disposition of exogenous 
progesterone after intramuscular 
administration in bitches. Am J Vet Res 
1990, 51:893–895.
Wilkens L. Masculinization of female fetuses 
due to the use of orally given progestins. J 
Am Med Assoc 1960, 172(10):1028–1032.
Authors  Autumn P . Davidson and Tomas W. 
Baker

Canine and Feline, Seventh Edition  1127
P
Prolapsed Gland of the Third Eyelid (Cherry Eye)
  BASICS
OVERVIEW
• Definition—prolapsed gland of the third 
eyelid.
• Pathophysiology—the gland is normally 
anchored by a fibrous attachment to the 
periorbita beneath the third eyelid. In cases of 
prolapse these attachments are weak, resulting 
in dorsal movement of the gland. Commonly 
occurs in dogs and rarely in cats; animals may 
have unilateral or bilateral prolapse.
• Dog—usually in young dogs (6 months to 
2 years of age); common breeds: American 
cocker spaniel, English bulldog, beagle, 
bloodhound, Lhasa apso, mastiff, shih tzu, 
other brachycephalic breeds.
• Cat—rare; occurs in Burmese, Persians, and 
has been reported in domestic shorthair cats.
SIGNS
• Oval, hyperemic mass protruding from 
behind the leading edge of the third eyelid in 
• May be unilateral or bilateral.
• May see signs of epiphora, hyperemic 
conjunctiva, keratitis, or blepharospasm.
• Additional swelling and hyperemia of the 
exposed gland can result from environmental 
exposure leading to irritation and desiccation.
• Congenital weakness of the attachment of 
the gland of the third eyelid.
• Inheritance unknown but considered 
complex and multigenic.
  DIAGNOSIS
• Scrolled or everted cartilage of the third 
eyelid—seen in Weimaraner, Great Dane, 
German shorthaired pointer, and other breeds 
in which the T-shaped cartilage of the third 
eyelid is rolled away from the surface of the 
cornea instead of conforming to the surface of 
the cornea.
• Neoplasia of the third eyelid—usually seen 
in older animals. Most common third eyelid 
neoplasms in the dog are adenocarcinoma, 
adenoma, and squamous cell carcinoma. May 
also see lymphoma or fibrosarcoma. Most 
common third eyelid neoplasms in the cat are 
adenocarcinoma followed by squamous cell 
carcinoma. A small incisional biopsy is 
indicated to differentiate.
• Orbital fat prolapse—may dissect anteriorly 
between the conjunctiva and globe; occasion-
ally occurs in the medial canthus.CBC/BIOCHEMISTRY/URINALYSIS
N/A
N/A
IMAGING
N/A
N/A
  TREATMENT
• Surgical replacement of the gland (various 
techniques can be performed)—see Suggested 
Reading.
• Gland excision contraindicated; gland can 
produce up to 50% (or more) of the aqueous 
tear film; puts patient at substantial risk for 
developing keratoconjunctivitis sicca as the 
dog ages. Excision may be considered if 
neoplasia is confirmed, although potential 
complications and risks should be discussed.
• Elizabethan collar—to prevent self-trauma.
• Topical anti-inflammatory medications, 
such as corticosteroids (if no corneal 
ulceration) or nonsteroidal anti-inflammatory 
medications—may be used before and after 
surgery.
• Topical lubricating medications (ointments 
or gels)—may be used to reduce environmen-
tal exposure causing irritation and/or 
desiccation.
N/A
  FOLLOW-UP
• Recurrence—5–20%, depending on the 
breed, with large-breed dogs (e.g., mastiff) 
having the highest recurrence rates; re-
replacement of the gland is encouraged.
• If unilateral, warn client that the other 
gland may also prolapse and that no 
preventive procedure or medication exists.
SYNONYMS
Cherry eye.
canine conjunctiva and nictitating membrane. In: Gelatt KN, Gilger BC, Kern T, eds., 
Veterinary Ophthalmology, 5th ed. Ames, IA: 
Wiley-Blackwell, 2013, pp. 945–975.
Multari D, Perazzi A, Contiero B, et al. Pocket 
technique or pocket technique combined 
with modified orbital rim anchorage for the 
replacement of a prolapsed gland of the third 
eyelid in dogs: 353 dogs. Vet Ophthalmol 
2016, 19:214–219.
Peruccio C. Diseases of the third eyelid. In: 
Maggs DJ, Miller PE, Ofri R, Slatter’s 
6th Ed. St. Louis, MOL Elsevier, 2018, 
pp. 178–184.
Sapienza JS, Mayordomo A, Beyer AM. 
Suture anchor placement technique around 
the insertion of the ventral rectus muscle for 
the replacement of the prolapsed gland of 
the third eyelid in dogs: 100 cases. Vet 
Ophthalmol 2014, 17:81–86.
Gilger BC, Kerns T, eds., Veterinary 
Ophthalmology, 5th ed Ames, IA: 
acknowledge the prior contribution of Brian 
C. Gilger.

1128  Blackwell’s Five-Minute Veterinary Consult  
P
Proptosis
  BASICS
OVERVIEW
• Forward displacement of globe, with eyelids 
trapped behind globe’s equator (see Web 
• Frequently acute and due to bite wounds, 
head trauma.
• Vision threatening.
• Immediate repositioning of globe critical.
• More common in brachycephalic breeds 
(shallow orbit, large palpebral fissure).
• May occur in any species or breed with 
severe enough traumatic force.
SIGNS
Possible Accompanying Signs
• Subconjunctival or intraocular hemorrhage.
• Pupil dilated or constricted.
• Intraocular inflammation (uveitis).
• Globe deviation/strabismus/rupture.
• Corneal ulceration/desiccation.
• Periocular bite wounds.
• Fractures of bony orbit or skull.
• Systemic injuries.
T rauma—primary cause; may be relatively 
minor force (e.g., restraint) in brachycephalic 
breeds; usually severe impact or trauma in 
other breeds.
  DIAGNOSIS
• Buphthalmia—globe enlargement; rarely acute.
• Exophthalmia—forward displacement of 
globe due to retrobulbar space-occupying 
lesion; may be acute, rarely peracute.
Normal, unless trauma-related abnormalities 
present.
IMAGING
Skull CT or radiographs—may show 
trauma-related fractures. Further diagnostic 
workup indicated if other systemic injuries.
  TREATMENT
• Prevent further trauma—lubricate cornea, 
Elizabethan collar.
• Stabilize patient and perform thorough 
systemic physical examination before surgery.
Repositioning the Globe
• As soon as safely possible.
• Performed under sedation and local 
anesthesia or general anesthesia.• Fluorescein—stain cornea prior to replacing 
globe.
• Lateral canthotomy—may ease tension on 
eyelids and allow easier globe repositioning; 
not always necessary.
• Engage eyelid margins with eyelid forceps 
(e.g., Von Graefe or Allis forceps) or strabismus/  
muscle hooks, pull eyelids forward and away 
from globe while protecting and gently 
pushing globe back into orbit (e.g., with 
lubricated scalpel blade handle), preventing 
forward traction on globe and optic nerve.
• Place 2–3 temporary tarsorrhaphy mattress 
sutures (sutures emerge from eyelid margin in 
line with meibomian gland openings) with 
stents; suture lateral canthotomy wound.
Eye Removal
With extensive globe or periocular tissue damage 
(loss of shape and turgor of ruptured globe, most 
conjunctival and muscle attachments severed), 
enucleation may be best option.
• Systemic and topical broad-spectrum 
antibiotics—until suture removal.
• Systemic corticosteroids—use initially; may 
be continued if marked periorbital/
retrobulbar swelling.
• Topical corticosteroids—treat uveitis or 
hyphema, if no corneal ulceration.
• Topical atropine—for intraocular 
inflammation or hemorrhage; relieve ciliary 
spasm and lower risk of synechiae.
corneal ulcerations.
• Systemic corticosteroids—do not use with 
peri- or retrobulbar infection.
  FOLLOW-UP
Suture removal—usually sequential, starting 
10–14 days after surgery. Reassess integrity of 
globe and vision.
Bilateral medial and/or lateral canthoplasty to 
shorten palpebral fissure and prevent future 
proptosis in brachycephalic breeds.
• Most patients retain dorsolateral strabismus 
and slight forward displacement of medial 
side of globe due to rupture of inferior 
oblique and medial rectus muscles. May 
improve with time.• Decreased tear production—perform 
Schirmer tear tests after suture removal.
• Corneal denervation causing neurotrophic 
keratitis with chronic ulceration, decreased 
corneal sensitivity.
• Exposure keratitis from forward displace -
ment of globe, decreased tear production, 
facial nerve palsy and/or corneal denervation 
(decreased blink reflex).
• Most affected eyes can be salvaged; if in 
doubt, reposition and try to salvage the globe; 
majority will be blind.
• Extensive tissue damage, avulsion of three 
or more extraocular muscles, facial and/or 
orbital fractures, and corneal or scleral 
rupture—grave prognosis for vision and globe 
salvage for cosmesis.
• Normal retinal vessels and optic nerve, 
normal intraocular pressure, and short time 
from occurrence to repair—relatively 
favorable prognosis for maintaining vision.
• Positive menace response, dazzle and/or 
pupillary light reflexes—good prognosis for 
maintaining vision (always observe indirect 
pupillary light reflex in healthy eye 
originating from injured eye!).
• Pupil size at time of injury—not an 
accurate prognostic indicator.
SEE ALSO
Orbital Diseases (Exophthalmos, 
Enophthalmos, Strabismus).
Miller PE. Ophthalmic emergencies. In: 
Maggs DJ, Miller PE, Ofri R, eds., Slatter’s 
Saunders, 2017, pp. 432–441.
Spiess BM, Pot SA. Diseases and surgery of 
the canine orbit. In: Gelatt KN, Gilger BC, 
Kern TJ, eds., Veterinary Ophthalmology, 
pp. 793–831.

Canine and Feline, Seventh Edition  1129
P
Prostate Disease in the Breeding Male Dog
  BASICS
OVERVIEW
• The prostate is the only accessory sex gland 
in the dog and is palpable per rectum as a 
bilobed oval gland with a median septum. 
• Dihydrotestosterone (DHT) stimulates 
growth of prostate gland; 5- α reductase in 
prostatic epithelial cells metabolizes serum 
testosterone to DHT.
Benign Prostatic Hyperplasia
• Commonly diagnosed in intact dogs—a 
result of diffuse, hormone-dependent, 
glandular, stromal hyperplasia and hypertrophy 
of prostate. • Cystic hyperplasia may occur 
later in disease process. • Contributing factors 
include age-associated changes in intraprostatic 
estrogen:androgen ratio, which potentiates 
hyperplastic response, and DHT-permissive 
growth of prostate. • Clinical effects minimal 
or absent in most dogs. • Renders prostate 
more susceptible to ascending infection and 
development of bacterial prostatitis.
Prostatitis/Prostatic Abscess
• Inflammation/infection of prostate. • Acute 
or chronic bacterial infection, abscess usually 
secondary to chronic bacterial prostatitis. • Also 
associated with benign prostatic hyperplasia 
(BPH) or retention cysts. • Bacterial coloniza -
tion is typically via ascending urinary tract 
pathogens; hematogenous spread possible. 
• Common isolates include Escherichia coli , 
Klebsiella , Pseudomonas , Pasteurella , streptococci, 
and staphylococci species. • Concurrent 
bacterial urinary tract infection is not always 
noted with chronic bacterial prostatitis. 
• Brucella canis  may be associated with acute or 
chronic prostatitis and has zoonotic potential. 
• Fungal prostatitis has been reported 
(Blastomyces  and Cryptococcus ).
Prostatic Cysts
• Within prostatic parenchyma, coalescing 
glandular/cystic hyperplasia and ductular 
occlusion (retention cysts) caused by estrogen 
effects (e.g., from Sertoli cell tumor) on prostatic 
epithelium. • Paraprostatic cysts are attached to 
prostate, lined by secretory epithelium, and 
variable in size; larger cysts may be trans -
abdominally palpable; almost always sterile.
Prostatic Neoplasia
• Prostatic adenocarcinoma (ACA) is most 
common; other tumor types include fibro -
sarcoma, leiomyosarcoma, and squamous cell 
carcinoma (SCC). • Prostatic transitional cell 
carcinoma (TCC) arise from the prostatic 
urethra and invade the prostate gland. • BPH 
is not a risk factor for prostatic neoplasia. 
• T umor development is androgen 
independent; castration is not protective. 
• T umors typically detected after metastatic 
spread as clinical signs occur late and early screening is unavailable. • ACA bone 
metastasis is common, typically to spine or 
pelvis; intraprostatic fibrosis with some areas 
of ossification and hyperplasia is seen.
• BPH—50% of intact dogs exhibit 
histologic evidence by 5 years of age, >95% 
by 9 years of age. • Prostatitis/prostatic 
abscess: common. • Prostatic cysts—
prevalence around 14%; 42% of these had 
evidence of bacterial infection. • Neoplasia—
prevalence 0.2–0.6% in general population, 
5–7% of dogs with prostatic disease.
• BPH—microscopic onset by 5 years of age.
• Prostatitis/prostatic abscess—any age; more 
common in adults. • Prostatic cysts—more 
common after 8 years of age. • Neoplasia—
mean age 10 years.
SIGNS
• Dogs with prostatic disease display 
overlapping clinical signs. • Many dogs are 
asymptomatic. • Dyschezia, tenesmus, 
constipation, ribbon-like stool with advanced 
disease. • Sanguinous urethral/preputial 
discharge. • Dysuria, hematuria, stranguria. 
• If mild, generally asymptomatic. 
• Hematuria and hemospermia are most 
common signs.
Prostatitis—Acute
• Systemic illness (vomiting, fever, 
inappetence). • Pyuria. • Stiff-legged gait.
Prostatitis—Chronic
• Recurrent/chronic urinary tract infection. 
• Stiff gait. • Infertility.
Prostatic Cyst
• If mild, generally asymptomatic. • If 
infected see signs associated with prostatitis.
• Emaciation. • Dyschezia. • Rear limb 
locomotory disturbance. • Lumbosacral pain.
Large, symmetrically enlarged, nonpainful 
prostate.
• Fever. • Dehydration. • Sepsis/shock. 
• Caudal abdominal pain. • Normal to 
enlarged, asymmetric, painful prostate.
• Symmetric, nonpainful, firm, normal size 
prostate. • May have fluctuant areas (focal 
cysts) on palpation.
• Symmetric, enlarged prostate with fluctuant 
areas; large cysts may preclude rectal 
palpation, enlarged prostate may be transabdominally palpable. • External signs 
of feminization if cyst formation is due to 
• Large, asymmetric, irregular painful 
prostate. • Rectal, abdominal, lumbosacral 
pain. • Palpable abdominal mass. 
• Lymphadenopathy (sublumbar).
Older, intact males.
PROSTATITIS
• BPH and/or prostatic cysts. • Breeding 
dogs may have higher risk for Brucella canis .
  DIAGNOSIS
Hematuria
• Urinary tract infection. • Thrombocytopenia. 
• T rauma. • Neoplasia.
TENESMUS
Colonic or rectal disease.
Hind Limb Gait/Locomotory Disturbance
• Arthritis. • Degenerative disc disease. 
• Neuromuscular disease.
Typically normal, except hematuria.
• Leukocytosis and neutrophilia  
(± immaturity and signs of toxicity). • Pyuria. 
• Bacteriuria. • Hematuria.
• Occasionally leukocytosis. • Pyuria. 
• Anemia (if hyperestrogenism present). 
• Biochemistry and urinalysis typically 
normal.
• Leukocytosis and neutrophilia. • Elevated 
alkaline phosphatase. • Pyuria. • Hematuria. 
• Atypical cells may be noted in urine 
sediment.
• Prostatic fluid culture—culture third 
ejaculate fraction or fine-needle aspirate of 
prostate; positive growth supports bacterial 
prostatitis. • Paired seminal fluid and 
urethral culture—prostatitis is confirmed 
when seminal fluid bacterial growth (in 
colony-forming units) is ≥100 times 
corresponding urethral/urine growth. 
• Semen evaluation—may be normal or 
hemospermic with BPH; neutrophils, 
phagocytized bacteria, variable degree of

1130  Blackwell’s Five-Minute Veterinary Consult  
P
reduced sperm motility and teratospermia 
with bacterial prostatitis. • Prostate-specific 
antigen/canine prostatic-specific esterase are 
not of clinical use in dogs. • Positive urine 
screening for cells with BRAF  gene 
mutations (CADET™ BRAF ) is highly 
sensitive and specific for the presence of 
prostatic urethral TCC.
IMAGING
• Abdominal ultrasound—detects size, 
homogeneity of prostate. Identifies focal 
parenchymal abnormalities (cysts or 
abscesses); loss of tissue homogeneity 
(prostatitis or neoplasia); regional lymph 
nodes and paraprostatic structures (para -
prostatic cysts). • Abdominal radiography—
bony metastases; degree of prostatomegaly. 
• Lack of prostatic mineralization in intact 
dogs with prostatomegaly has a negative 
predictive value of 96% for neoplasia. 
• Retrograde cystourethrogram—evaluates 
urethral compression, identifies contrast 
leakage.
• Prostatic wash to obtain culture and 
cytologic evaluation of prostatic fluid. 
• Ultrasound-guided fine-needle aspirate—
cytologic evaluation may distinguish between 
BPH, prostatitis, and neoplasia; aspiration of 
active infections may seed periprostatic and 
subcutaneous tissues; aspiration of cysts rarely 
provides clinical resolution • Ultrasound-
guided transabdominal biopsy—provides 
definitive diagnosis for BPH, prostatitis, 
  TREATMENT
• Temporary indwelling urethral catheter 
placement in animals with severe pain or 
urethral obstruction. • Analgesia. • Stool 
softeners and low-residue diets to ease 
• T reat symptomatic dogs. • Castration is 
curative. • Finasteride is medical treatment of 
choice in breeding animals; decreases 
prostatic weight and diameter; prostate 
returns to pretreatment size 8 weeks after 
stopping therapy; typically used to reduce 
clinical signs permitting frozen semen stores 
to be generated; castrate when desired doses 
of semen are stored.
Prostatitis—Acute and Chronic
• Antimicrobials (based on culture and 
sensitivity) and that penetrate blood–prostate 
barrier (e.g., veterinary fluoroquinolone for 
Gram-negative organisms and clindamycin or a macrolide for Gram-positive organisms). 
Chloramphenicol and trimethoprim–
sulfonamide are additional options. 
• Antimicrobials with poor penetration through 
an intact blood–prostate barrier should not be 
used. • Antimicrobials should be administered 
for a minimum of 4 weeks in acute cases, and 
up to 6 weeks for chronic cases. • Response to 
therapy should be monitored based on clinical 
signs, prostatic size and architecture, return of 
semen quality. Repeat cultures are not 
recommended unless poor initial response. 
• Finasteride may be considered to treat 
underlying prostatic pathology in dogs with 
future breeding intent. Castration is advised for 
nonbreeding animals and those that respond 
poorly to appropriate therapy.
Prostatic Abscess
Prostatic abscesses should be percutaneously 
drained with ultrasound guidance after 
administration of perioperative antimicrobials.
• Castration—treatment of choice. 
• Finasteride may be useful if associated with 
BPH. • Remove source of estrogen if 
squamous metaplasia. • Large solitary 
cysts—surgical marsupalization and 
castration. • Paraprostatic cysts—may be 
surgically excised. • Aspiration and drainage 
of cysts—not associated with resolution; fluid 
should be cultured.
• Differentiation between ACA and TCC will 
determine appropriate treatment (see specific 
chapters). • Urine culture. • A piroxicam trial 
should always be offered with or without 
• Regular B. canis  testing for breeding 
animals (minimum every 6 months). 
• Proactive semen freezing at young age prior 
to onset of prostatic disease/BPH.
• Finasteride 0.1 mg/kg PO q24h to a 
maximum of 5 mg PO q24h. 
• Antimicrobials—drug used and duration 
will vary with culture results and disease 
process; chronic prostatitis requires lipid-
soluble antibiotics to reach parenchyma (e.g., 
enrofloxacin 10–20 mg/kg PO q24h) for 4–6 
weeks.
• Estrogens and progestogens—decrease 
prostatic mass via negative feedback on serum testosterone concentrations; however, toxic 
side effects are common and their use is not 
recommended. • Nonsteroidal anti-inflamm -
atory drugs—may be associated with hepatic 
and/or renal dysfunction, gastrointestinal 
ulceration. • T rimethoprim–sulfamethoxa-
zole—may be associated with keratoconjunc-
tivitis sicca, thrombocytopenia, and hepatic 
necrosis.
Deslorelin (Suprelorin)—not approved for 
this use in United States; not recommended 
for dogs intended for breeding; dramatically 
suppresses hypothalamic–pituitary–gonadal 
axis and testosterone production.
  FOLLOW-UP
• Serial prostatic fluid cultures to document 
antimicrobial efficacy. • Semen evaluation 
should be performed 70 days after resolution 
of illness in any breeding dog. • Serial 
abdominal ultrasound to evaluate response to 
treatment. • Dogs testing positive for 
brucellosis should not be used for breeding.
• BPH generally responsive to finasteride. 
• Chronic prostatitis more refractory to 
medical management; castration may be 
indicated. • Poor prognosis for prostatic 
• Sertoli cell tumor. • Infertility. • Recurrent 
• ACA = adenocarcinoma.
• BPH = benign prostatic hyperplasia.
• DHT = dihydrotestosterone.
• TCC = transitional cell carcinoma.
Weese J, Blondeau J, Boothe D, et al. 
International Society for Companion Animal 
Infectious Diseases (ISCAID) guidelines for 
the diagnosis and management of bacterial 
urinary tract infections in dogs and cats. Vet 
J 2019, 247:8–25.
Author  Sophie A. Grundy
Consulting Editor  Erin E. RuncanProstate Disease in the Breeding Male Dog  (continued)

Canine and Feline, Seventh Edition  1131
P
  BASICS
OVERVIEW
• Prostatic cysts in dogs include those 
associated with diffuse epithelial cystic change 
from androgen-dependent benign prostatic 
hyperplasia (BPH), cavitating retention cysts 
within the prostatic parenchyma, fluid-filled 
lesions with a distinct capsule, and para -
prostatic cysts that are cavitating, fluid-filled 
lesions with a distinct capsule located outside 
of the prostatic parenchyma. Prostatic cysts 
may range in diameter from a few millimeters 
to more than 20 cm.
• Paraprostatic cysts usually arise craniolateral 
to the prostate, displacing the bladder 
cranially and ventrally, or caudal to the 
prostate in the pelvis. Prostatic cysts may 
represent dilated embryonal remnants of the 
wolffian ducts.
• Pathogenesis is unknown, but the 
occurrence of retention cysts in dogs with 
estrogen-secreting Sertoli cell tumors causes 
speculation that these cysts are dilations of 
prostatic acini secondary to estrogen-induced 
• Male intact dogs; rare occurrence in 
castrated dogs.
• Age range 2–12 years, mean age 8 years.
• Large dogs more commonly affected than 
small dogs.
SIGNS
• Lethargy and anorexia.
• Tenesmus if the cyst compresses the 
rectum.
• Dysuria if the cyst compresses the urethra.
• Sanguinous urethral discharge in the 
presence of BPH.
• BPH.
• Androgenic hormones.
• Estrogenic hormones.
  DIAGNOSIS
• BPH—distinguished by ultrasound.
• Prostatic abscess—distinguished by 
ultrasound and semen culture.
• Distended urinary bladder—distinguished 
by cystocentesis, imaging.
• Caudal abdominal mass of undetermined 
origin—distinguished by imaging.CBC/BIOCHEMISTRY/URINALYSIS
No abnormalities.
• Examination of prostatic fluid collected by 
ejaculation or prostatic massage confirms 
absence of infection.
• Culture and cytology of cyst fluid collected 
by ultrasound-guided fine-needle aspiration 
or by aspiration at surgical exploration reveals 
sterile clear or sanguineous fluid consistent 
with prostatic fluid.
IMAGING
Retrograde contrast urethrocystography 
followed by prostatic ultrasonography 
confirms presence, location, echo-texture, and 
size of prostatic cysts, and differentiates 
retention cysts from paraprostatic cysts.
Collection of prostatic fluid by ejaculation 
followed by prostatic imaging is recommended 
prior to fine-needle aspiration of cystic fluid 
to rule out bacterial infection.
Epithelial cysts within the prostatic 
parenchyma occur with parenchymal 
hypertrophy and hyperplasia; squamous 
metaplasia of the ducts and alveoli may be 
present. Retention cysts and paraprostatic 
cysts are lined by a single layer of prostatic 
epithelium or fibrous connective tissue and 
contain clear to sanguineous fluid with fibrin.
  TREATMENT
• Intraprostatic cysts (epithelial, retention) 
respond to prostatic involution via castration 
or the 5 α-reductase inhibitor finasteride. 
Large cysts may be drained percutaneously 
with ultrasound guidance prior to initiation 
of finasteride therapy.
• Large retention cysts and paraprostatic cysts 
should be partially or completely surgically 
resected, depending on adherence to 
surrounding structures, or marsupialized and 
drained for 1–2 months.
• Simple drainage of the cyst is not 
recommended as persistence of the capsule 
may result in recurrence.
Prostatic parenchyma and diffuse epithelial 
cysts involute following treatment with 
finasteride 0.1–1 mg/kg PO q 24 h, not to 
exceed 5 mg/dog, for 2–4 months or as long as the dog remains intact to treat BPH. 
Finasteride prevents conversion of 
testosterone to dihydrotestosterone, causing 
prostatic involution without adversely 
affecting libido or spermatogenesis. BPH 
recurs following cessation of finasteride 
therapy. Paraprostatic cysts do not respond to 
finasteride treatment.
N/A
  FOLLOW-UP
• Imaging assessment of cyst size at 4-week 
intervals following treatment.
• Standard postoperative monitoring of 
marsupialized stoma.
Disorders of the canine prostate. In: Canine 
and FelineTheriogenology. Philadelphia, 
PA: Saunders, 2001, pp. 337–355.
Rawlings CA, Mahaffey MB, Barsanti JA, 
et al. Use of partial prostatectomy for 
treatment of prostatic abscesses and cysts in 
dogs. J Am Vet Med Assoc 1997, 
211:868–871.
anatomy, pathology, diagnosis, and 
treatment. Theriogenology 2008, 
70:375–383.
Stowater JL, Lamb CR. Ultrasonographic 
features of paraprostatic cysts in nine dogs. 
Vet Radiol Ultrasound 1989, 30:232–239.
White RAS, Herrtage ME, Dennis R. The 
diagnosis and management of paraprostatic 
and prostatic retention cysts in the dog. 
J Small Anim Pract 1987, 28:551–574.
Author  Bruce W. Christensen
would like to acknowledge the prior 
contribution of Carl A. Osborne.

1132  Blackwell’s Five-Minute Veterinary Consult  
P
Prostatitis and Prostatic Abscess
  BASICS
Acute Prostatitis
Infection of the canine prostate with bacteria, 
mycoplasmas, or fungi with systemic signs of 
fever, anorexia, lethargy, pain, and 
inflammatory exudate in prostatic fluid. 
Abscessation is variable, but occasionally 
rupture into the peritoneal cavity, causing 
sepsis, shock, and death.
Chronic Prostatitis
Subclinical infection of the canine prostate in 
absence of prostatic abscessation and 
polysystemic signs. Affected animals are 
asymptomatic except for inflammatory 
exudate in the prostatic fluid, which causes 
infertility. Chronic prostatitis may occur after 
or independently of acute prostatitis.
• Predisposing pathology is benign prostatic 
hyperplasia (BPH), which occurs under the 
influence of dihydrotestosterone (DHT) in 
more than 80% of intact male dogs >5 years 
of age (see Benign Prostatic Hyperplasia).
• Infection of the hypertrophied canine 
prostate develops most commonly from 
ascending flora—rarely from blood-borne 
bacteria or from penetrating wounds. The 
prostate of intact dogs constantly secretes 
prostatic fluid, which is deposited into the 
prostatic urethra and then flows into the 
urinary bladder and out of the penile urethra. 
With prostatitis, prostatic fluid containing 
blood, inflammatory exudate, and 
microorganisms is deposited into the urinary 
bladder and discharged intermittently from 
the tip of the penis.
• Hemic/lymphatic/immune—mature or 
immature neutrophilia in acute prostatitis.
• Polysystemic—septic shock if prostatic 
abscesses rupture, fever, and focal or 
generalized peritonitis.
• Urinary—dysuria if the enlarged prostate 
compresses the urethra; deposition of 
prostatic fluid with inflammatory exudate 
into the urinary bladder.
• Reproductive—pain at copulation and 
reduction in libido; infertility from infected 
prostatic fluid in the ejaculate.
Intact male dogs >5 years of age are at highest 
risk, though overall incidence is low. Infection 
is reported in 40% of dogs with prostatic 
disease. Prostatitis in castrated males is 
exceedingly rare.
Species
All breeds.
Mean age range 7–11 years.
Intact male dogs; may occur secondary to 
prostatic neoplasia in castrated dogs.
SIGNS
• Lethargy/depression.
• Pyrexia.
• Pain at prostatic or caudal abdominal 
palpation.
• Sanguineous or purulent urethral discharge.
• Stiff hind limb gait.
• Septic shock.
• Dysuria.
• Sanguinous or purulent urethral discharge.
• Dysuria.
CAUSES
• Infection of the hypertrophied prostate 
with ascending urethral flora (most 
commonly E. coli ), anaerobic bacteria, or 
Mycoplasma .
with systemic bacterial infection, including 
Brucella canis.
• Systemic or local puncture wound infection 
with Blastomyces dermatitidis .
• Intact male.
• BPH and, less commonly, prostatic 
• Historical androgen or estrogen 
• Impaired host defense mechanisms.
  DIAGNOSIS
• BPH distinguished by prostatic cytology or 
semen culture.
• Prostatic cysts distinguished by ultrasound 
and semen culture.
• Prostatic neoplasia distinguished by 
ultrasound, tissue biopsy, and castrated  
state.
• Abdominal mass or abscess distinguished by 
abdominal imaging.
• CBC—include immature neutrophilia and 
toxic neutrophils; immature neutropenia may 
occur with sepsis. Most dogs with chronic 
prostatitis have a normal CBC.• Serum chemistry—abnormalities are 
variable with acute prostatitis, normal in most 
• Urinalysis—hematuria, pyuria, and causative 
microbes arise from deposition of infected 
prostatic fluid into the urinary bladder.
• Cytology, and culture of whole semen or 
the prostatic fluid fraction of semen or fluid 
collected at prostatic massage yields 
inflammatory exudate with microorganisms. 
Normal prostatic fluid should contain 
<100,000 cfu/mL, and <5 leukocytes per hpf 
following fluid centrifugation.
• Although infection with B. canis  is 
uncommon, because of the zoonotic potential 
of this infection, serology is recommended.
IMAGING
Survey radiography of the caudal abdomen, 
retrograde urethrocystography, and prostatic 
ultrasonography can evaluate prostatic size, 
echotexture, and detection of cavitating 
prostatic lesions.
• Collection and evaluation of prostatic fluid 
in seminal plasma or by prostatic massage.
• Ultrasound-guided percutaneous fine-
needle aspirate of the prostate.
• Gross pathology of the infected prostate 
includes focal, multifocal, or diffuse enlarge -
ment, variable loss of symmetry of the dorsal 
median raphe, and variable presence of 
fluid-filled abscesses within or on the surface 
of the gland.
• Infection causes suppurative (bacterial) or 
granulomatous (fungal) inflammation, which 
may be focal, multifocal, or diffuse. Abscesses 
contain purulent fluid exudate.
• Biopsy of the infected prostate is not 
recommended because biopsy may result in 
the spread of infection to adjacent tissues.
  TREATMENT
• Acute prostatitis, prostatic abscess, and 
rupture of prostatic abscesses into the 
peritoneal cavity are potentially life-
threatening emergencies that can lead to septic 
shock and death. Hospitalize affected patients 
and collect diagnostic samples immediately.
• Chronic prostatitis patients may be seen as 
outpatients for diagnostic procedures and 
started on therapy when laboratory results are 
• Dogs with acute prostatitis or prostatic 
abscess should receive IV antimicrobial drugs.
• If abscess rupture and peritonitis is 
suspected, administer therapy for septic shock.

Canine and Feline, Seventh Edition  1133
P
ACTIVITY
Breeding should be avoided until bacteria 
have been cleared from the prostatic fluid.
• Castration is recommended for 
nonbreeding dogs with prostatitis and/or 
prostatic abscess, as castration induces 
permanent prostatic involution.
• If maintenance of breeding potential is 
desired, long-term treatment with finasteride 
(see Benign Prostatic Hyperplasia) is 
recommended to induce prostatic involution. 
BPH recurs over time in intact male dogs 
after treatment with finasteride is 
discontinued, and BPH increases risk of 
recurrence of prostatitis.
• Surgical management of prostatic abscesses 
should be deferred until after initiation of 
antimicrobial therapy and prostatic involution; 
involution is associated with resolution of smaller 
abscesses, often making surgery unnecessary.
• Castration is recommended for induction 
of prostatic involution in nonbreeding dogs 
with prostatitis; castration should be deferred 
until after identification and treatment (for at 
least 1 week) of the causative bacterial/fungal 
agent.
• Surgical drainage with subsequent packing 
of the cavity with omentum has been 
associated with the fewest adverse sequelae 
among surgical treatments. Referral to a 
surgical specialist is recommended.
Eradicating Infection
• Choice of antimicrobial agent is based on 
culture of the prostatic fluid and the ability of 
the antibiotic to cross the blood–prostate 
barrier. Antibiotics should be lipophilic, not 
highly protein-bound, and be a weak base.
• Antibiotics of choice—fluoroquinolones, 
trimethoprim, chloramphenicol, and 
macrolides. In acute prostatitis, the blood–
prostate barrier is disrupted and almost any 
antibiotic will penetrate the prostatic 
parenchyma initially, but once healing has 
begun one of the preferred antibiotics 
discussed should be used.
• Antibiotic therapy should be administered 
for 4 weeks with repeat culture of prostatic 
fluid performed 1–2 weeks after the end of 
antibiotic treatment.Inducing Prostatic Involution
• T reatment of choice in nonbreeding dogs 
for inducing permanent prostatic involution 
is castration.
• Alternatively, the 5 α-reductase inhibitor 
finasteride (0.1–1 mg/kg PO q 24 h; not to 
exceed 5 mg/dog) for 2–4 months induces 
involution of the prostatic parenchyma and 
diffuse epithelial cysts and abscesses.
• Finasteride prevents conversion of 
testosterone to DHT, thereby causing 
affecting libido or spermatogenesis.
• BPH recurs following cessation of 
finasteride therapy; intact males should be 
maintained on finasteride.
Estrogens and androgens cause squamous 
metaplasia of the prostate and BPH, 
Long-term therapy with trimethoprim may 
lead to keratoconjunctivitis sicca or hypo  - 
  FOLLOW-UP
• Serial evaluation of semen culture, cytology, 
and prostatic imaging.
• Intervals between reevaluations vary with 
severity of signs, presence of an abscess, 
selection of castration or finasteride therapy 
for prostatic involution, and use of the dog in 
a breeding program. Intervals between 
evaluations range from 1 to 8 weeks, with 
recheck recommended prior to breeding.
• Continue patient monitoring until the dog 
has been castrated.
Castration is recommended in nonbreeding, 
affected dogs to induce prostatic involution, 
resolution of BPH, and prevention of 
recurrent infection. Breeding males should be 
• Recurrence of infection if prostatic 
involution is not induced or antibiotic 
therapy is discontinued prematurely.
• Surgical drainage of abscesses is associated 
with many complications, including urinary 
incontinence, recurrent abscessation, 
hypoproteinemia, scrotal edema, anemia, 
sepsis, and shock.EXPECTED COURSE AND PROGNOSIS
• Prognosis is good to excellent except in the 
case of rupture of prostatic abscesses into the 
• Castration prevents recurrence and 
improves prognosis.
is associated with complications and a poorer 
prognosis than medical/surgical induction of 
prostatic involution.
When prostatic fluid is infected, blood, 
inflammatory exudate, and microbial 
organisms may reflux into the urinary bladder, 
which, if detected in a urine sample collected 
by cystocentesis, may be misinterpreted as 
primary urinary tract infection.
Rare; B. canis  and Blastomyces dermatitidis  
have been isolated from the urine of dogs 
with prostatic infection, but human infection 
from these sources has not been reported.
SEE ALSO
• Benign Prostatic Hyperplasia.
• BPH = benign prostatic hyperplasia.
Root Kustritz MV. Collection of tissue and 
culture samples from the canine reproductive 
tract. Theriogenology 2006, 66:567–574.
available online(continued)  Prostatitis and Prostatic Abscess

1134  Blackwell’s Five-Minute Veterinary Consult  
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Prostatomegaly
  BASICS
Abnormally large prostate gland determined by 
rectal or abdominal palpation, abdominal 
radiography, or prostatic ultrasonography. The 
enlargement can be symmetrical or asymmetrical, 
painful or nonpainful. Normal prostate size varies 
with age, body size, castration status, and breed so 
assessment of enlargement is subjective.
Enlargement can result from epithelial cell 
hyperplasia or hypertrophy (e.g., benign prostatic 
hyperplasia [BPH]), neoplasia of prostatic 
epithelium or stroma, cystic change within the 
prostatic parenchyma, or inflammatory cell 
infiltration (e.g., acute and chronic bacterial 
prostatitis and prostatic abscess).
• Urinary.
• Dog.
• Typically occurs in middle-aged to older 
males.
SIGNS
• May be none.
• Straining to defecate.
• Dysuria.
• Urethral outflow obstruction.
CAUSES
• BPH.
• Squamous metaplasia.
• Sarcoma.
• Acute or chronic bacterial prostatitis.
• Prostatic abscess.
• Prostatic cyst.
• Castration lowers the risk of BPH and 
bacterial prostatitis.
• Risk of adenocarcinoma may be increased 
threefold in castrated dogs.
  DIAGNOSIS
• BPH—typically causes nonpainful 
symmetrical enlargement of the prostate 
gland; not found in neutered dogs.
• Primary or metastatic neoplasia—typically 
causes painful, nonsymmetric enlargement of 
the prostate gland; weight loss, impaired 
appetite, rear limb weakness observed in some 
patients; suspect neoplasia in castrated dogs.• Acute bacterial prostatitis—typically results 
in slight-to-moderate symmetric or 
nonsymmetric enlargement of the prostate 
gland with prostatic pain. Fever, impaired 
appetite, rear limb weakness, and painful 
abdomen observed in some patients.
• Chronic bacterial prostatitis—signs similar 
to those seen in dogs with acute prostatitis or 
those related to recurrent lower urinary tract 
infection (e.g., dysuria and hematuria). 
Systemic signs less common than in acute 
bacterial prostatitis; bacterial prostatitis 
uncommon in castrated dogs.
• Prostatic abscess—may result in signs 
similar to those in patients with acute or 
chronic prostatitis; abscess rupture causes 
fever and caudal abdominal pain.
• Prostatic cysts—may be associated with 
palpable caudal abdominal mass, straining to 
urinate, or straining to defecate; patient may 
also be asymptomatic.
• CBC normal in patients with BPH.
• Leukocytosis in patients with prostatic 
abscess and bacterial prostatitis, occasionally 
with chronic bacterial prostatitis and prostatic 
• High bilirubin and alkaline phosphatase in 
some patients with prostatic abscess.
• Hematuria in patients with BPH.
• Pyuria, hematuria, proteinuria, and 
bacteriuria in patients with bacterial 
prostatitis
• Pyuria, hematuria, proteinuria, and, 
occasionally, neoplastic cells in dogs with 
Serum canine prostate-specific arginine 
esterase concentration may be high in dogs 
with BPH.
IMAGING
• Abscess or cyst—hypoechoic or anechoic 
lesions with distal enhancement.
• Acute bacterial prostatitis—uniform 
prostatic echogenicity.
• BPH—uniform prostatic echogenicity; 
small fluid-filled cysts in some patients.
• Chronic bacterial prostatitis—focal or 
diffuse hyperechogenicity.
• Prostatic neoplasia—focal to multifocal areas 
of coalescing echogenicity and acoustic 
shadowing (if dystrophic mineralization occurs).
• Examination of prostatic fluid obtained by 
ejaculation or prostatic massage may reveal 
red blood cells with BPH, neutrophils with 
prostate infection, or neoplastic cells with 
carcinoma• Bacterial culture of prostatic fluid typically 
reveals >100,000 cfu/mL in dogs with 
• Needle biopsy of the prostate with ultrasound 
guidance provides visualization of the area to be 
sampled and increases the likelihood of 
obtaining a diagnostic sample; take care to 
avoid iatrogenic rupture of a prostatic abscess.
  TREATMENT
• Varies with the cause of prostatomegaly.
• Surgical castration—indicated in 
symptomatic nonbreeding dogs with BPH 
and after acute infection resolves in dogs with 
• Surgical drainage—indicated in dogs with 
prostatic abscess or large prostatic cysts.
BPH
If castration is not desired, the following 
drugs may produce a temporary response:
• Finasteride 0.1–0.5 mg/kg/day PO; not to 
exceed 5 mg/dog, for as long as the dog 
• Medroxyprogesterone 3 mg/kg SC once.
• Osaterone acetate 0.25 mg/kg PO once 
daily for 7 days.
• Delmadinone acetate 3 mg/kg SC once.
• Deslorelin acetate (SC implant 
administered every 6–12 months).
Bacterial Prostatitis
Choose antibiotics on the basis of anti -
bacterial susceptibility testing of the isolated 
pathogen and ability of the antibiotic to 
diffuse into prostatic fluid in therapeutic 
concentrations. Good choices for the latter 
include fluoroquinolones, trimethoprim–
sulfamethoxazole, chloramphenicol, and 
macrolides. T reatment should be for a 
minimum of 4 weeks.
Prostatic Carcinoma
Cox-2 inhibitors such as piroxicam and 
carprofen have been shown to prolong 
acceptable quality of life an average of 6 
months compared to 3 weeks in nontreated 
dogs. These are used sometimes in 
combination with chemotherapeutic agents 
such as mitoxantrone, vinblastine, or 
metronomic chlorambucil. Referral to an 
oncologist is recommended.
Long-term administration of 
medroxyprogesterone and trimethoprim–
sulfamethoxazole can cause diabetes mellitus 
and keratoconjuctivitis sicca, respectively.

Canine and Feline, Seventh Edition  1135
P
  FOLLOW-UP
• Abdominal radiographs or prostatic ultra -
sonography to assess efficacy of treatment in 
BPH, prostatic carcinoma, or bacterial 
prostatitis.
• Urine and prostatic fluid culture to access 
efficacy of treatment in patients with bacterial 
• Subfertility.
• Dysuria.  MISCELLANEOUS
SEE ALSO
• Adenocarcinoma, Prostate.
48(4):701–719.Smith J. Canine prostatic disease: a review of 
contributions of Carl A. Osborne and Jeffrey 
S. Klausner.(continued)  Prostatomegaly

1136  Blackwell’s Five-Minute Veterinary Consult  
P
Protein-Losing Enteropathy
  BASICS
• A disease process characterized by excessive 
loss of protein into the gastrointestinal (GI) 
lumen. • Protein-losing enteropathy (PLE) may 
be associated with primary GI diseases (e.g., 
inflammatory bowel disease, intestinal 
lymphoma, or intestinal lymphangiectasia) and 
systemic disorders (e.g., fungal disease or 
congestive heart failure [CHF]).
• Under physiologic conditions, two-thirds of 
normal protein loss in dogs occurs through the 
small intestine. • Plasma proteins that leak into 
the GI lumen are rapidly digested into 
constituent amino acids that can be reabsorbed 
and used for the synthesis of new proteins. • This 
normal loss of plasma proteins can be accelerated 
by GI mucosal disease or by increased leakage of 
lymph into the GI lumen. • GI protein loss is 
associated with loss of both albumin and 
globulin, often resulting in panhypoproteinemia. 
• In response to increased GI protein loss, the 
liver increases albumin synthesis. However, the 
liver cannot increase albumin synthesis to more 
than twice the normal output. • When protein 
loss exceeds protein synthesis, hypoproteinemia 
results. • Hypoproteinemia causes decreased 
plasma oncotic pressure, which may lead to 
hemodynamic changes, effusion into body 
cavities or peripheral edema.
• Coagulation—patients with PLE lose 
antithrombin and other anticoagulants, resulting 
in a hypercoagulable state which may lead to 
thromboembolic events such as pulmonary 
thromboembolism (PTE). • GI—primary GI 
disease may be associated with diarrhea, 
vomiting, or weight loss. • Hemodynamic—
decreased oncotic pressure leading to cavitary 
effusion. • Lymphatic—lymphangiectasia. 
• Respiratory—dyspnea due to pleural effusion 
or PTE. • Skin—subcutaneous edema.
GENETICS
PLE due to specific underlying causes is 
suspected to be hereditary based on an 
increased prevalence in specific dog breeds.
• Unknown. • Many dogs with subacute or 
acute gastroenteritis have transient PLE.
N/A
Species
Soft-coated wheaten terrier, Basenji, Yorkshire 
terrier, and Norwegian lundehund.
Any age.Predominant Sex
No predilection.
SIGNS
Clinical signs are variable.
• Chronic diarrhea, weight loss, sarcopenia, 
and lethargy are most frequently reported. 
However, many dogs with PLE have normal 
stools. • Vomiting is uncommon. • Dogs can 
be presented for apparent weight gain or 
abdominal distension.
• Ascites, dependent edema, and dyspnea 
from pleural effusion may be detected in 
patients with marked hypoproteinemia. 
bowel loops, though this is uncommon.
CAUSES
Disorders of Lymphatics
• Intestinal lymphangiectasia. • GI lymphoma. 
• Granulomatous infiltration of the small bowel. 
• CHF leading to lymphatic hypertension.
Diseases Associated with Increased 
Mucosal Permeability or Mucosal 
• Viral gastroenteritis—parvovirus and 
others. • Bacterial gastroenteritis—salmonel-
losis and others. • Fungal gastroenteritis—
histoplasmosis and others (note: serum 
globulin concentrations can be within the 
reference interval due to increased production 
secondary to massive antigenic stimulation). 
• Parasitic enteritis—hookworms, whipworms, 
and others. • Inflammatory bowel disease—
lymphocytic-plasmacytic, eosinophilic, or 
granulomatous gastroenteritis. • Adverse food 
reactions. • Mechanical enteropathies—
chronic intussusception, chronic foreign 
body, and others. • Intestinal neoplasia—
lymphoma, adenocarcinoma, and others. 
• Gastric or intestinal ulcers.
• GI disease. • Lymphatic disease. • Heart 
disease.
  DIAGNOSIS
• Hypoalbuminemia due to hepatic failure—
often associated with normal or increased serum 
globulin concentration. Hepatic enzyme activity 
may be increased, serum BUN, cholesterol, and 
glucose may be decreased, and serum pre- and 
postprandial bile acids concentrations may be 
increased. • Hypoalbuminemia due to protein-  
losing nephropathy (PLN)—mild in patients 
with fever or hyperadrenocorticism, moderate to 
severe in patients with glomerulonephritis or 
amyloidosis; commonly associated with a 
normal or increased serum globulin concentration; ruled out by a normal urine 
protein:creatinine ratio. • Hypoalbuminemia 
due to severe blood loss: excluded by assessment 
of the CBC and a thorough physical 
examination; in some cases a test for fecal occult 
blood may be necessary. • Starvation is a rare 
cause of hypoalbuminemia.
• Hypoalbuminemia and frequently 
hypoglobulinemia (panhypoproteinemia). 
• Normal or increased serum globulin 
concentration in some cases, if the underlying 
disease is associated with chronic antigenic 
stimulation (e.g., immunoproliferative 
enteropathy of the basenji). • Hypocalcemia. 
• Hypocholesterolemia. • Lymphopenia may 
be seen with lymphangiectasia.
• Increased fecal α1-protease inhibitor 
concentration (must be assessed in naturally 
passed and freshly frozen fecal samples from 3 
consecutive days). • Once PLE has been 
identified as the cause of the hypoalbuminemia, 
specific tests may be useful to determine the cause 
of PLE: multiple fecal examinations to rule-out 
intestinal parasitism as a cause of PLE; serum 
cobalamin and folate concentrations to diagnose 
small intestinal dysbiosis or cobalamin deficiency.
IMAGING
• Thoracic radiographs may show evidence for 
cardiac, mediastinal, or fungal disease. 
• Abdominal radiographs may show evidence 
for a mechanical enteropathy (i.e., foreign 
body, intussusception, or other). • Abdominal 
ultra sound may show evidence for a mechanical 
enteropathy or other causes of PLE. 
• Abdominal ultrasound is helpful for evaluating 
the pattern of intestinal wall layering that can be 
associated with a variety of enteropathies. 
Hyperechoic mucosal striations (“tiger stripe” 
effect), mucosal speckles, and a hyperechoic line 
within the mucosa that runs parallel to the 
submucosa are common findings in dogs with 
intestinal lymphangiectasia. • Echocardiogram 
may show evidence for cardiac disease.
• Broad-spectrum anthelminthic agent to treat 
for potential parasitism. • Elimination diet trial 
using a novel or hydrolyzed protein source to 
rule out food sensitivity. One study in a group 
of soft-coated wheaten terriers suggests a 
hydrolyzed protein diet may be the best choice 
in dogs with PLE. • Histoplasma antigen test 
(serum or urine) and rectal mucosal scraping in 
geographic regions where histoplasmosis is 
endemic. • Gastroduodenoscopy and colono  - 
scopy—to visualize the GI mucosa and to 
collect endoscopic biopsies for histopathologic 
evaluation. Visualization of white “plaques” 
(e.g., chylomicron distended lacteals) along the 
mucosa suggests lymphangiectasia. 
• Abdominal exploratory laparotomy may show 
dilated intestinal lymphatics and allows for 
full-thickness biopsies of intestines and lymph

Canine and Feline, Seventh Edition  1137
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nodes. • Fecal α1-protease inhibitor concen -
tration to document excessive GI protein loss. 
Assays are species-specific and currently only an 
assay for measurement of α1-protease inhibitor 
in dogs is available through the GI Laboratory 
at Texas A&M University. Samples from 3 
consecutive defecations need to be collected in 
special preweighed fecal tubes that can be 
sourced from the GI Lab.
• In dogs with PLE due to lymphangiectasia, 
gross findings may include dilated lymphatics 
that are visible as a web-like network 
throughout the mesentery and serosal surface. 
• May see small yellow-white nodules and 
foamy granular deposits adjacent to lymphatics 
(lipogranulomas). • Lacteal dilatation, villous 
blunting, and crypt lesions (e.g., dilatation, 
cysts, abscesses) are the most consistent 
findings on histopathology in dogs with 
lymphangiectasia and PLE. • PLE due to other 
causes may show lesions specific for the disease.
  TREATMENT
Inpatient or outpatient medical management 
depending on the severity of clinical signs at 
• With clinical signs due to edema or effusion 
from severe hypoalbuminemia, albumin 
transfusion, or colloids (such as hetastarch) 
may be considered to increase plasma oncotic 
pressure. Both human and canine albumin can 
provide a temporary increase in serum 
albumin, but human albumin transfusion may 
be associated with adverse reactions in dogs. 
• Abdominocentesis to remove ascites or 
pleurocentesis to remove pleural effusion is 
indicated in cases where effusion has led to 
respiratory compromise. • Consider placement 
of an esophageal feeding tube in hyporexic 
patients to meet increased caloric demands.
ACTIVITY
Normal
DIET
• May need to be modified depending on the 
underlying cause of PLE. • If lymphangiectasia 
is diagnosed or highly suspected, an ultra-low-
fat diet, containing 20 g fat/1,000 kcal or less, is 
indicated. It should be noted that there are 
currently no commercial diets lower than 20 g 
fat/1,000 kcal and one study has suggested that 
an even lower fat content is beneficial.
Prepare clients for long-term therapy; 
spontaneous cures are rare.
• Hypoalbuminemia increases postoperative 
morbidity because of slow wound healing. 
• Some causes of PLE (e.g., intussusception, chronic foreign body, and some intestinal 
neoplasms), however, require surgical 
• There is no pharmacologic therapy for PLE 
itself. Instead, the underlying cause of PLE 
must be addressed.
• However, patients with PLE also lose 
antithrombin and other anticoagulants and 
can be hypercoagulable. Thus, patients should 
be treated with a platelet aggregation inhibitor: 
◦ In dogs or cats—clopidogrel bisulfate (1–4 
mg/kg PO q24h in dogs; 18.75 mg/cat PO 
q24h, which equals one-fourth of a 75 mg 
tablet). ◦ In dogs—low-dose aspirin (0.5 mg/
kg PO q12h; use an 81 mg tablet of aspirin 
and put into the barrel of a 10 mL syringe, add 
8.1 mL of water and shake until completely 
dissolved to make a 10 mg/mL solution; 
discard unused portion immediately).
• Aspirin and clopidogrel should not be used 
• Clopidogrel should not be used with 
NSAIDs, phenytoin, torsemide, or warfarin.
Bleeding may be enhanced in patients treated 
with platelet aggregation inhibitors that have 
to undergo surgery.
N/A
• Diuretics such as furosemide (1 mg/kg PO 
q12h) in combination with spironolactone 
(1 mg/kg PO q12h) have been used by some 
clinicians to control edema, pleural effusion, and 
ascites. However, they do not work consistently 
in patients with PLE because of decreased 
plasma oncotic pressure and may be associated 
with side effects. • There are anecdotal reports 
about the use of the long-acting somatostatin 
analogue octreotide in dogs with PLE, but no 
clinical trials have been completed to date and 
no specific dosing regimen has been suggested.
  FOLLOW-UP
Check body weight, serum albumin 
concentration, and evidence of recurrent clinical 
signs (i.e., pleural effusion, ascites, and/or 
edema). Frequency depends on the severity of 
the condition. Monitor serum cobalamin 
concentration if patient was hypocobalaminemic 
and supplemented with cobalamin.
• Thromboembolic events, especially PTE. 
• Respiratory difficulty from pleural effusion 
or PTE. • Severe protein-calorie malnutrition. 
• Prognosis is guarded and depends on the 
underlying cause. Smaller breed dogs carry a 
more favorable prognosis because nutritional 
support is easier to perform. • The primary 
disease cannot be treated in many cases.
Soft-coated wheaten terriers may have PLN 
in conjunction with PLE and should be 
evaluated accordingly.
N/A
Some GI parasites have zoonotic potential.
N/A
SYNONYMS
N/A
SEE ALSO
• CHF = congestive heart failure. 
• GI = gastrointestinal. 
drug. • PLE = protein-losing enteropathy. 
http://vetmed.tamu.edu/gilab/
Craven MD, Washabau RJ. Comparative 
pathophysiology and management of 
protein-losing enteropathy. J Vet Intern 
Med 2019, 33:383–402.
Dossin O, Lavoue R. Protein-losing 
enteropathies in dogs. Vet Clin North Am 
Small Anim Pract 2011, 41:399–418.
Simmerson SM, Armstrong PJ, Wunschmann 
A, et al. Clinical features, intestinal 
histopathology, and outcome in protein-
losing enteropathy in Yorkshire terrier dogs. 
J Vet Intern Med 2014, 28:331–337.
available online(continued)  Protein-Losing Enteropathy

1138  Blackwell’s Five-Minute Veterinary Consult  
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  BASICS
• Urinary protein detected by dipstick 
analysis, urinary protein:creatinine ratio 
(UP:C ≥0.4 in cats or ≥0.5 in dogs), urinary 
albumin:creatinine ratio (UA:C >30 mg/g), 
or 24-hour urine protein content ( > 20 mg/
kg). UP:C of 0.2–0.4 in cats and 0.2–0.5 in 
dogs is borderline.
• Microalbuminuria (MA) is the abnormal 
presence of low concentrations of albumin 
in the urine (1–30 mg/dL), below the 
limit of detection of standard urine 
dipsticks.
• Prerenal—greater than normal delivery of 
low-molecular-weight plasma proteins to 
glomeruli.
• Renal, glomerular—excessive loss of larger 
molecular weight proteins (e.g., albumin) 
across the glomerular basement membrane 
(GBM) secondary to altered permselectivity 
of glomeruli.
• Renal, tubular—reduced tubular 
reabsorption of proteins.
• Postrenal—exudation of blood or plasma 
into lower urinary tract.
• Renal/urologic—chronic glomerular 
proteinuria causes progressive tubular 
damage resulting in chronic kidney 
disease (CKD).
• Cardiovascular—systemic hypertension.
glomerular proteinuria can lead to edema 
and/or hypercoagulability. Hypercoagulability 
is brought about by vascular stasis, hyper -
fibrinogenemia, platelet abnormalities, loss of 
antithrombic substances, and an increase in 
procoagulant factors. The pathogenesis of 
edema involves both inappropriate renal 
sodium retention and decreased plasma 
oncotic pressure.
GENETICS
Familial nephropathies associated with 
glomerular proteinuria have been described 
in several breeds of dogs; in only a few has 
the mode of inheritance been established: 
Samoyed (X-linked), English cocker spaniel 
(autosomal recessive), bull terrier (autosomal 
dominant), Dalmatian (autosomal 
dominant), Bernese mountain dog 
(autosomal recessive), Brittany spaniel 
(autosomal recessive), bullmastiff 
(autosomal recessive), Newfoundland 
(autosomal recessive), soft-coated wheaten 
terrier (complex), Chinese shar-pei 
(suspect autosomal recessive). Doberman 
pinscher, Rottweiler, Pembroke Welsh 
corgi, beagle, English foxhound, and others.INCIDENCE/PREVALENCE
• In a study of urinalysis data from 500 dogs, 
the prevalence of proteinuria was approx -
imately 19%.
• The prevalence of MA was 25% in dogs 
and 25% in cats. Prevalence increased with 
None, however an association may be observed 
with some infectious diseases that are regional.
Species
Glomerular proteinuria may be the initial 
manifestation of several familial renal diseases 
(see Genetics).
Proteinuria can occur at any age. Familial 
renal diseases tend to occur in younger 
animals; acquired glomerular proteinuria 
more likely in middle-aged or older animals
Varies with different diseases
SIGNS
• Vary with underlying cause and severity of 
• Patients with glomerular proteinuria are 
frequently asymptomatic or have signs 
attributable to underlying diseases.
• Weight loss and lethargy; animals with 
pulmonary thromboembolism may have 
acute dyspnea.
• Patients with lower urinary tract (LUT) 
disorders may have dysuria, pollakiuria, 
inappropriate urination, and/or hematuria.
• May have edema or abdominal distention.
• May have oral ulceration (if uremic), edema 
or cavitary effusion, or changes in pulse 
quality (if thromboembolic).
CAUSES
Prerenal Proteinuria
Overload proteinuria—tubular resorptive 
capacity exceeded by large amounts of 
low-molecular-weight plasma proteins in 
glomerular filtrate (e.g., excessive hemolysis 
or rhabdomyolysis, neoplastic production of 
paraproteins or Bence Jones proteins).
Renal Proteinuria
• Functional proteinuria—strenuous exercise, 
fever, hypothermia, seizures, or venous 
congestion.
• Glomerulonephritis (e.g., immune 
complex-mediated, membranous, membrano -
proliferative, proliferative), minimal change 
disease, hereditary nephritis, amyloidosis, 
rosis, glomerulosclerosis.• All glomerular diseases can be associated 
with severe proteinuria, subsets of immune 
complex-mediated (particularly membrano -
proliferative and membranous) may be 
associated with higher magnitude proteinuria 
than others.
• T ubular dysfunction resulting in failure of 
tubular protein reabsorption is associated 
with mild-to-moderate proteinuria.
Postrenal Proteinuria
Hemorrhage or inflammation of the 
urogenital tract.
• Chronic inflammatory (e.g., infectious and 
immune-mediated) and neoplastic diseases can 
lead to development of glomerulonephritis or 
amyloidosis. Examples include dirofilariasis, 
ehrlichiosis, borreliosis, babesiosis, chronic 
bacterial infections (e.g., endocarditis, 
pyoderma), pyometra, bartonellosis, feline 
immunodeficiency virus, mast cell tumor, 
lymphosarcoma, hyperadrenocorticism, and 
• Chronic hyperlipidemia.
• Multiple myeloma can produce Bence Jones 
  DIAGNOSIS
Differentiate prerenal, postrenal, and renal- 
tubular from glomerular causes.
• Urine dipstick and sulfosalicylic acid (SSA) 
tests allow qualitative and semiquantitative 
assessment of urine protein content. Results 
are affected by urine concentration and must 
be interpreted in context of urine specific 
gravity. Low urine protein (trace or 1+) may 
be normal in a concentrated urine sample.
• The dipstick lacks specificity (dog, 69%; cat, 
31%) and sensitivity (dog, 54%; cat, 60%).
• False-positive test results occur when urine is 
highly alkaline (pH >8–9) or when the dipstick 
is immersed in the urine for a prolonged time.
• Low concentrations of Bence Jones proteins 
or gamma globulins may not be detected by 
urine dipstick.
• SSA turbidometric test results are falsely 
increased by radiographic contrast media, 
penicillins, sulfisoxazole, or the urine 
preservative thymol.
• SSA test results are falsely decreased by very 
alkaline urine and increased by uncentrifuged 
urine.
• If proteinuria is detected by these methods, 
the urine sediment should be evaluated for 
hematuria, pyuria, and/or bacteriuria. 
Hematuria alone typically does not increase 
urine albumin content above the negligible 
range (i.e., >1 mg/dL) or the UP:C above 0.4

Canine and Feline, Seventh Edition  1139
P
until there is a color change in the urine. 81% 
of dogs with pyuria had normal UP:C.
• To determine persistence, repeat the urine 
protein screening test in proteinuric patients that 
initially have a normal urine sediment or have 
been treated for urinary tract inflammation or 
hemorrhage. If proteinuria is transient and the 
urine sediment is normal, consider functional 
proteinuria or false-positive test results.
• Although not all animals with glomerular 
disease are hypoalbuminemic, glomerular 
proteinuria should be suspected when 
proteinuria and hypoalbuminemia are 
concurrent. As disease progresses, clinico -
pathologic changes consistent with 
glomerular disease may develop.
• Urine protein should be quantified in dogs 
and cats that have hypoalbuminemia and/or 
repeatedly positive urine dipstick or SSA tests in 
absence of LUT hemorrhage or inflammation. 
The UP:C is the preferred because more is 
known about use of this test and it is technically 
easier to perform than 24-hour urine collections.
• MA is detected in dogs using a point-of-
care immunoassay or quantitation using an 
immunoassay. MA is an early predictor of 
proteinuria. If repeatedly positive, and if the 
concentration is increasing, the patient may 
be at risk for glomerular disease.
• Thoroughly evaluate an animal for an 
underlying disease when persistent proteinuria 
is believed to be of glomerular origin.
• Urine and serum protein electrophoresis 
may identify pre-glomerular proteinuria in 
patients with monoclonal gammopathies or 
urinary immunoglobulin light chains (Bence 
Jones proteins).
IMAGING
Ultrasound and radiographs may reveal an 
underlying infectious, inflammatory, or 
neoplastic disease process or evidence of LUT 
disease. Ultrasound may show structural 
changes suggesting primary renal disease (e.g., 
loss of corticomedullary distinction, hyper -
echogenicity, and irregular surface margin) or 
evidence in support of LUT disease.
• Blood pressure should be monitored in 
patients with persistent renal proteinuria.
• Renal biopsy is needed to specifically 
diagnose the glomerular disease when an 
underlying disease cannot be identified or 
proteinuria has persisted following treatment 
of an underlying disease.
• Vary with cause of proteinuria.
• Biopsy from an animal with glomerular 
proteinuria may reveal any of the 
following: glomerulonephritis (e.g., 
immune complex-mediated, membranous, 
membranoproliferative, proliferative), 
minimal change disease, hereditary nephritis, amyloidosis, podocyopathy, focal 
segmental glomerulosclerosis, glomerulo-  
sclerosis.
• Animals with tubular proteinuria most often 
have a degree of tubulointerstitial nephritis.
• Postrenal proteinuria would be expected to 
have inflammatory, neoplastic, or polypoid 
lesions.
  TREATMENT
Most can be managed as outpatients. 
Inpatient care may be required during select 
diagnostic evaluation (renal biopsy) or when 
there are complications associated with 
uremia, thromboembolism or edema in 
patients with glomerular proteinuria.
Physical therapy and exercise may limit 
formation of edema in patients with 
glomerular proteinuria and hypoalbuminemia.
ACTIVITY
Activity should not be restricted in animals 
with proteinuria.
DIET
If glomerular disease is suspected, feed a diet 
formulated for kidney disease.
It is important to determine the cause of 
persistent proteinuria, which may indicate the 
presence of kidney disease. Renal proteinuria 
is a risk factor for progressive kidney disease, 
thromboembolism, and edema.
<2 g/dL) present unique challenges to 
An angiotensin receptor blocker (ARB) or 
inhibitor should be administered. Preliminary 
evidence suggests telmisartan (ARB) may be 
more efficacious in reducing proteinuria than 
ACE inhibitors. Combined use of an ARB 
and an ACE inhibitor should be done with 
caution as this is associated with a greater risk 
of death in people. Use of aldosterone 
antagonists in management of proteinuria 
needs further investigation but may be 
indicated for patients that have increased 
aldosterone concentrations following treatment with an ACE inhibitor or ARB. 
Animals with hypertension may be controlled 
with telmisartan alone, however some may 
require addition of a calcium channel blocker 
(e.g., amlodipine) to control both hyper -
tension and proteinuria. Supplementation 
with n-3 polyunsaturated fatty acid (PUFA) 
should be considered in dogs, and possibly 
cats, with glomerular proteinuria when the 
diet being fed does not have a reduced 
n-6/n-3 PUFA ratio that approximates 5:1. 
Dogs with glomerular disease should also be 
given low-dose aspirin or clopidogrel as 
thromboprophylaxis.
There are no known contraindications in 
animals with proteinuria.
Drugs highly bound to albumin may have an 
altered effect if hypoalbuminemia is present. 
The use of warfarin as an anticoagulant 
should be avoided. With hypoalbuminemia 
or azotemia, higher doses of furosemide may 
be required to mobilize edema effectively; 
however, it should be used with extreme 
caution.
There are no known important drug 
interactions in dogs with proteinuria other 
than the previously mentioned concern with 
highly protein-bound drugs.
ARB and ACE inhibitor are alternatives to 
each other.
  FOLLOW-UP
• UP:C, urinalysis, systemic arterial blood 
pressure and serum albumin, creatinine and 
monitored at least quarterly.
• Use the UP:C to assess progression of 
disease. Response to treatment should be 
evaluated for several months after resolution 
of any underlying disease. Reduction of UP:C 
to <0.5 (dog) or <0.2 (cat) without 
inappropriate worsening of renal function is 
considered a therapeutic success. However, 
this target is often not achieved and a 
reduction in UP:C of >50% is the 
recommended alternate target.
• Monitor serum creatinine—reduced 
proteinuria or reduced albuminuria that is 
concurrent to a rising serum creatinine may 
reflect deteriorating renal function.
• Because UP:Cs may vary, 2–5 serial 
assessments may be needed to evaluate 
response to treatment or progression in 
patients with glomerular proteinuria. 
Alternatively, the UP:C can be measured in a (continued)  Proteinuria

1140  Blackwell’s Five-Minute Veterinary Consult  
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sample that has been pooled by adding equal 
aliquots of 2–3 samples that have been 
collected and refrigerated over a 48-hour time 
period.
• When given an ACE inhibitor or an ARB, 
dogs with stage 1 or 2 CKD can have an 
increase in serum creatinine of up to 30% 
without warranting a change in treatment. 
Worsening of renal function in dogs with 
stage 3 or 4 CKD should be avoided. During 
therapy the serum potassium concentration 
should not be >6 mmol/L and the systolic 
blood pressure should not be <120 mmHg.
Annual urinalyses and UP:C are 
recommended. Repeat in 2–4 weeks if 
proteinuria is detected. Patients with 
persistent proteinuria or MA of glomerular 
origin should be evaluated more thoroughly 
for underlying causes of glomerular injury. 
Potential underlying causes should be 
eliminated or managed. If proteinuria 
persists, potential underlying causes have 
been managed appropriately or underlying 
causes were not identified, consider renal 
biopsy.
• Edema.
• Thromboembolism.
• Progressive kidney disease.
• Poor wound healing.
• Vary with the cause of proteinuria.
• Postrenal and prerenal proteinuria should 
resolve following resolution of inciting causes.
• Most diseases associated with renal tubular 
proteinuria are progressive.
• The rate of progression varies and 
spontaneous remissions have been reported. 
Animals with persistent glomerular proteinuria may develop renal tubular damage 
resulting in advanced CKD and eventual 
uremia and death. Some dogs die shortly after 
the initial detection of proteinuria, while 
others remain alive for years. Dogs with 
nephrotic syndrome and/or azotemia may 
have a shorter survival.
Hypoalbuminemia, hypoglobulinemia (rare), 
hypercholesterolemia, low antithrombin III, 
thrombocytosis, hyperfibrinogenemia, edema, 
thromboembolism, and systemic hypertension.
considered in young animals with glomerular 
range proteinuria.
Proteinuria does not have a zoonotic 
potential. However, glomerular proteinuria 
can occur with a variety of infectious diseases, 
some of which could have a zoonotic 
potential.
Some drugs used in the treatment of diseases 
associated with proteinuria may be contra -
indicated in pregnancy.
SYNONYMS
None
SEE ALSO
• Nephrotic Syndrome.• Pyuria.
• ACE = angiotensin-converting enzyme.
• ARB = angiotensin receptor blocker.
• GBM = glomerular basement membrane.
• LUT = lower urinary tract.
• MA = microalbuminuria.
• PUFA = polyunsaturated fatty acid.
• SSA = sulfosalicylic acid.
• UA:C = urinary albumin:creatinine ratio.
• UP:C = urine protein:creatinine ratio.
Med 2013, 27(suppl.1):S27–S43.
Lees GE, Brown SA, Elliot J, et al. 
Assessment and management of proteinuria 
in dogs and cats: 2004 ACVIM forum 
Intern Med 2005, 19:377.
Littman MP , Daminet S, Grauer GF , et al. 
Consensus recommendations for the 
diagnostic investigation of dogs with 
suspected glomerular disease. J Vet Intern 
Med 2013, 27(suppl.1):S19–S26.
Pressler B, Vaden S, Gerber B, et al. Consensus 
guidelines for immunosuppressive treatment 
of dogs with glomerular disease absent a 
pathologic diagnosis. J Vet Intern Med 2013, 
27(suppl.1):S55–S59.
available onlineProteinuria  (continued)

Canine and Feline, Seventh Edition  1141
P
Protothecosis
  BASICS
OVERVIEW
Algal infection in warm-blooded animals.
• Skin/exocrine. • Gastrointestinal. • Nervous. 
• Dogs—young female adult, medium- to 
large-breed dogs, boxer and collie are over -
represented. • Cats—uncommon, usually 
cutaneous form.
SIGNS
Dogs
• Intermittent and chronic large bowel diarrhea 
with fresh blood. • Chronic weight loss. 
• Acute onset blindness. • Neurologic disease; 
deafness, seizures, ataxia. • Cutaneous lesions.
Cats
• Chronic cutaneous or mucous membrane 
ulceration with few systemic signs.
Dogs
• Gastrointestinal, ocular, or neurologic disease 
most common. • Severe weight loss and 
debilitation. • Hemorrhagic colitis, vomiting, 
anorexia. • Blindness due to chorioretinitis and/or 
detached retinas. • CNS—depression, ataxia, 
vestibular signs, seizures and/or paresis. 
• Cutaneous—ulcers and crusts on the extremities 
and mucosal surfaces.
Cats
• Large cutaneous nodules on the face or 
limbs.
• Prototheca wickerhamii  and P . zopfii  
(genotype 1 and 2 )—single-celled 
achlorophyllous blue-green algae 
(Chlorophyta). • Dogs—usually P . zopfii  
(75-90%); P . wickerhamii  infection may also 
occur. • Cats—usually P . wickerhamii . • Basis 
for the pathogenicity of Prototheca  spp. 
unknown; likely traumatic inoculation. 
• Organism—ecological niche is sewage; 
contaminants of water, soil, and food; 
occasionally isolated from fecal samples. 
• Dogs and humans—depressed cell-mediated 
immunity may predispose to infection.
  DIAGNOSIS
• Systemic or subcutaneous mycoses. 
• Mycobacterioses. • Neoplasia. • Pythiosis. 
• Actinomycosis. • Nocardiosis.CBC/BIOCHEMISTRY/URINALYSIS
CSF tap—pleocytosis with mononuclear 
cells; increased protein; organisms.
Cytology
• Rectal or colonic mucosa, vitreous humor, 
CSF , cutaneous aspirations. • Organisms—
unicellular, nonpigmented, oval or round cell 
walls often appear folded; diagnostic character -
istic is endospore formation with internal 
septation in two planes.
• Biopsy specimens—identification of organisms 
is diagnostic. • Organisms—3–30  μm in 
diameter. P . wickerhamii  round with sporangia 
(7–13  μm) with up to 50 spherical sporangio -
spores. P . zopfii  are usually oval or cylindrical and 
produce sporangia (14–25  μm) with up to 20 
sporangiospores.
Culture
• Blood agar or Sabouraud’s dextrose agar. 
• Specific identification by selective agars or 
biochemical tests in culture (susceptibility to 
clotrimazole, sugar, and alcohol assimilation 
tests) or immunohistochemistry.
PCR Assays
PCR and DNA to determine species. 
Specimens can be taken from biopsies, CSF , 
or urine.
Dogs
• Small granulomatous foci or hemorrhagic 
ulcers—found in many organs, especially 
kidneys. • Nodular thickening of the 
gastrointestinal mucosa with ulceration. 
• Nonspecific inflammatory foci 
surrounding organisms or pyogranulomas—
poorly organized; mixed with other 
Cats
• Cutaneous masses—localized; extend deep 
into subcutaneous tissues; consist of 
granulomatous inflammation and mixed-cell 
inflammation; with numerous fungal 
  TREATMENT
• Dogs—surgical excision and combination 
drug therapy. • Cats—excision of localized 
cutaneous masses is primary therapeutic 
modality.  MEDICATIONS
• Amphotericin B—use for localized disease 
after surgical excision; 0.25–0.5 mg/kg IV 
three times weekly until 8 mg/kg cumulative 
dose; lipid formulation 1 mg/kg every other 
day until 12 mg/kg cumulative dose. 
• Concurrent administration of tetracycline 
or amikacin may provide synergistic effect. 
• Itraconazole 5–10 mg/kg PO twice daily—
used with amphotericin B, or as sole agents 
for less life-threatening disease. 
• Clotrimazole. • Potassium iodide. 
• Amphotericin B cream or clotrimazole 
enemas for colitis. • Nystatin 100,000–
150,000 IU PO q8h for at least 90 days.
  FOLLOW-UP
• Difficult to eradicate with drug therapy. 
• No definitive therapeutic protocol. 
• Dogs—prognosis guarded to grave (median 
survival 4 months). • Cats—prognosis fair to 
good for cutaneous disease if lesions completely 
excised.
None
https://www.academia.edu/8599426/
Protothecosis_an_emerging_algal_disease_of_
humans_and_animals
Pressler BM. Protothecosis and clorellosis. In: 
pp. 696–701.
Mercuriali E, Bottero E, Abramo F , et al. 
Canine protothecosis in the North of Italy: 
4 cases (2009–2011), 22nd ECVIM-CA 
Congress, Maastricht, 2012.
Silveira CS, Cesar D, Keating MK. A case of 
Prototheca zopfii  genotype 1 infection in a 
dog ( Canis lupus familiaris ). Mycopatholgia 
2018, 183(5):853–858.
Resnick

1142  Blackwell’s Five-Minute Veterinary Consult  
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Pruritus
  BASICS
Pruritus (itch) is an unpleasant sensation that 
causes the clinical symptom of scratching, 
rubbing, hair pulling, and/or licking.
Keratinocytes, mast cells, eosinophils and 
lymphocytes interact with neuronal cells via 
the release of cytokines, neurotrophins, and 
neuropeptides. The sensation of itch is 
conducted via the peripheral nervous system to 
the sensory cortex. Other factors can modify 
the perception of pruritus at this level. Pruritus 
is an adaptive protective mechanism, however 
excessive itch can lead to cutaneous damage. 
Identification and treatment or removal of the 
causative agent(s) is the most important aspect 
of long-term control. Avoidance or reduction 
of long-term medical therapy should be 
pursued when possible. Chronic cases may be 
best handled by a dermatologist.
• Skin/exocrine/neuronal.
SIGNS
• Scratching, licking, biting, rubbing, hair 
pull, or chewing.
• Variable evidence of self-trauma and 
cutaneous inflammation.
• Non-well-demarcated alopecia with or 
without excoriations, and without obvious 
gross inflammation may be the only sign.
CAUSES
• Parasitic—fleas, Sarcoptes  spp., Demodex  
spp., Otodectes  spp., Notoedres  spp., 
Cheyletiella  spp., Trombicula  spp., lice, 
Pelodera  spp., endoparasite migration.
• Allergic—flea allergy, atopic dermatitis, food 
allergy, contact allergy, drug allergy, bacterial 
hypersensitivity, malassezia hypersensitivity.
• Bacterial/fungal— Staphylococcus  spp. and 
Malassezia pachydermatis ; rarely dermatophyte 
(Trichophyton  is more pruritic than other 
dermatophytes).
• Miscellaneous—primary and secondary 
seborrhea, calcinosis cutis, cutaneous 
neoplasia, immune-mediated dermatoses, and 
endocrinopathies are variably pruritic; 
psychogenic diseases may also be associated 
with pruritus (especially in cats).
  DIAGNOSIS
• Pruritus often causes alopecia.
• Alopecia without pruritus may accompany 
endocrine diseases. Some animals excessively 
lick themselves without the owner’s knowledge.
• Demodicosis, dermatophytosis, superficial 
pyoderma (bacteria), Malassezia  dermatitis, 
immune-mediated dermatoses, seborrhea, 
some cutaneous neoplasms, and unusual 
diseases such as leishmaniasis may cause 
alopecia with varying degrees of inflammation 
and pruritus.
• History is paramount for determining the 
diagnostic workup.
• Severe pruritus that keeps the patient and 
owner awake may suggest scabies, allergies 
(flea allergy/infestation, food allergy, atopic 
diseases) or Malassezia  dermatitis. All but the 
latter typically have an acute onset.
• Uncomplicated atopic diseases (dermatitis, 
rhinitis, conjunctivitis, asthma) are steroid- 
responsive and may manifest seasonally, but 
may progress to nonseasonal pruritus of the 
face, feet, ears, forelimbs, axillae, and caudal 
body.
• Flea-allergic and food-allergic animals may 
be predisposed to atopic diseases and may 
show similar signs. Food allergy is the least 
common of these three differentials.
N/A
Miscellaneous Procedures
• Identification and treatment of the 
underlying cause of pruritus is of paramount 
importance. It is common for multiple causes 
to be present concurrently and this can 
significantly complicate the workup and 
management of pruritus.
• Skin scrapes, epidermal cytology, and 
dermatophyte cultures
• A skin biopsy is useful when the lesions 
associated with pruritus are unusual, an 
immune-mediated dermatosis is suspected, or the 
history and physical findings do not correlate.
Allergy Testing
• Allergy testing does not diagnose atopic 
disease: The presence of positive test results 
does not diagnose that allergy is the cause or 
even a contributory cause of pruritus. Results 
must be carefully correlated with the patient’s 
history and physical examination.
• T wo methods for allergy testing—
intradermal and serum:
◦ Intradermal testing remains the gold standard 
and the preferred method for allergy testing.
◦ Serum tests for allergy measure serum 
IgE and do not measure localized IgE found 
in the skin. Patients with symptoms of 
atopic disease but negative on testing are 
diagnosed as having “atopic-like disease.”
• Positive reactions identified on testing are 
correlated with the history, in order to 
formulate allergen-specific immunotherapy 
solution (ASIT). The choice of allergens is 
based on the patient’s history, test results, 
local allergen exposure, and the veterinarian’s experience in treating allergies; not just the 
highest reactive allergens in the testing panel 
should be selected. Administration of 
immunotherapy may be via either subcutane-
ous or sublingual routes.
Trial Courses of Treatment 
as a Diagnostic Tool
• A trial course of therapy for scabies may be 
appropriate in some animals; canine scabies 
can be difficult to diagnose and skin scrapes 
are often negative.
• Laboratory tests (serum, hair, saliva) 
cannot be used for the diagnosis of food 
allergy; a properly performed strict dietary 
trial must be conducted. Novel protein diets 
based on the patient’s history or hydrolysate 
diets should be fed during the testing period. 
Careful client counseling to avoid all treats, 
supplements, chews, and flavored 
medications is necessary for a diet trial to 
succeed. Diet trials should be continued 
until the patient improves or for a duration 
of 8–10 weeks. Challenge with the original 
diet is a critical part of the test, and 
demonstrates that improvement was not due 
to concurrent therapy (e.g., relief of parasites, 
resolution of infection).
  TREATMENT
• More than one disease can contribute to 
itching.
• Secondary infections are common and may 
result in self-perpetuation of pruritus.
Topical Therapy
• Topical therapy is helpful for pruritic 
patients.
• Colloidal oatmeal—duration of effect is 
usually less than 2 days.
• Topical antihistamines have not 
demonstrated efficacy.
• Topical anesthetics may offer only a very 
short duration of effect.
• Topical corticosteroids—can be effective. 
But if used excessively, can cause localized and 
systemic side effects.
• Antimicrobial shampoos help control 
bacterial and/or yeast infections that cause 
itching; they can be excessively drying, 
necessitating use of moisturizers.
• Lime sulfur is mildly antipruritic as well as 
being antiparasitic, antibacterial, and 
antifungal.
• Therapy is complex and depends on the 
etiology.

Canine and Feline, Seventh Edition  1143
P
• Parasite prevention/treatment—fleas, 
scabies, demodicosis.
• ASIT—atopic disease.
• Chronic medical therapy with 
corticosteroids, cyclosporine, lokivetmab, or 
oclacitinib without evaluation by a 
dermatologist should be avoided.
• Corticosteroids affect many biological 
responses associated with pruritus. For acute 
relief, oral prednisone/prednisolone results in 
significant benefit for 2–5 days but rarely 
causes significant side effects.
• Cyclosporine 5 mg/kg/day initially; every 
other day maintenance—very useful in the 
treatment of atopic dermatitis. Adverse effects 
include gastrointestinal upset, oral papilloma, 
gingival hyperplasia, and hirsuitism. Not 
useful for quick relief due to its long lag phase 
(4–6 weeks).
• Oclacitinib 0.4–0.6 mg/kg twice daily for 
14 days, then 0.4–0.6 mg/kg q24h—fast 
acting without the common side effects of 
prednisone. Useful for temporary control of 
pruritus. Not for use in dogs less than 12 
months of age; may cause a mild, dose-
dependent reduction in hemoglobin, 
hematocrit, and reticulocyte counts as well as 
decreases in leukocytes. Potential for immune 
suppression, demodicosis, recurrent pyoderma, 
exacerbation of neoplastic conditions and 
pneumonia. Agitation with use reported. Avoid 
use at higher than recommended dosage.
• Lokivetmab 2 mg/kg—caninized mono -
clonal antibody against interleukin 31; for 
dogs only. Rapid onset (within 3 days from 
administration) and duration of effect 
between 2 and 8 weeks; effective in 60–70% 
of dogs with pruritus. Few side effects 
reported, including anaphylaxis, transient 
lethargy, and behavioral changes. Efficacy 
may be diminished by development of an 
immune response to this biologic medication 
and/or secondary infection.
• Fatty acids—block formation of inflamm -
atory mediators; require 6–8 weeks of 
administration for maximum effect.CONTRAINDICATIONS
• Some topicals will exacerbate pruritus: 
monitor treatment response.
• Corticosteroids should be avoided in cases 
of pruritus caused by an infectious etiology.
• Client frustration is common.
• Scabies is curable.
• Food allergy is manageable without 
medications if a proper food trial is conducted.
• Atopic dermatitis disease is a progressive 
common cause of pruritus and ASIT is the only 
therapy that can safely manage the disease alone 
or in combination with other medications.
• Corticosteroids—potentially significant 
long-term side effects.
• Cyclosporine—serum drug levels should be 
measured at least once initially in cats and in 
dogs if the maintenance dosage required to 
control symptoms is above the standard 
recommendation.
• Oclacitinib—long-term use associated with 
potential immunosuppression.
  FOLLOW-UP
• Patient monitoring as well as client 
communication are imperative.
• Many different unrelated diseases may 
contribute to pruritus and the control of one 
disease does not mean that other causes 
cannot remain.
• Multiple etiologies such as Malassezia  
dermatitis, flea bite allergy, atopic dermatitis, 
and pyoderma are commonly present in a 
single patient. Elimination of these may not 
be enough to significantly reduce the 
pruritus. Animals with both food allergy and 
atopic disease may do well during the winter 
season with a hypoallergenic diet only to 
become pruritic during the warmer months 
in association with atopic dermatitis.• Patients receiving chronic medication 
should be evaluated every 3–12 months for 
potential side effects as well as the occurrence 
of new contributing factors.
• Skin scrapes and other tests that may have 
been negative or normal during the original 
workup should be repeated if symptoms 
return.
• Complications and/or gradual loss of 
efficacy are not uncommon with chronic 
• ASIT = allergen-specific immunotherapy 
solution.
Gram WD. Pruritus, atopic dermatitis and 
pyoderma. In: Gram WD, Milner R, 
Lobetti R, eds., Chronic Disease 
Management For Small Animals. Hoboken, 
NJ: Wiley-Blackwell, 2018, pp. 25–38.
Olivry T, DeBoer DJ, Favrot C, et al. 
T reatment of canine atopic dermatitis: 2015 
updated guidelines from the International 
Committee on Allergic Diseases of Animals 
(ICADA). BMC Vet Res 2015, 11:210.
Santoro D. Therapies in canine atopic 
dermatitis: an update. Vet Clin North Am 
Small Anim Pract. 2019, 49(1):9–26.
Authors  W. Dunbar Gram and Domenico 
Santoro
Resnick
available online(continued)  Pruritus

1144  Blackwell’s Five-Minute Veterinary Consult  
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Pseudoephedrine/Phenylephrine Toxicosis
  BASICS
OVERVIEW
• Syndrome resulting from exposure to 
excessive levels of pseudoephedrine or 
• Present in various concentrations in a 
variety of over-the-counter (OTC) cold and 
allergy products.
Any species may be affected, but dogs are 
most commonly involved in accidental 
SIGNS
• Mydriasis, panting, hyperthermia, 
agitation/hyperactivity, tachycardia, 
hypertension are common. Other signs 
include vomiting, vocalization, tremors, 
disorientation, or lethargy.
• Head-bobbing, sinus arrhythmias, scleral 
hemorrhage, or seizure-like activity are 
possible. Acute collapse may follow.
• Signs of acute intoxication may persist 1–3 
days, depending on dose ingested.
• Severe cases may progress to disseminated 
intravascular coagulation (DIC), myoglobin -
uremia/uria with secondary renal injury, or 
permanent CNS dysfunction.
• Pseudoephedrine is a synthetic salt of 
ephedrine and is an indirect sympatho -
mimetic amine.
• Phenylephrine is a synthetic 
sympathomimetic amine chemically related 
to ephedrine and pseudoephedrine. 
Phenylephrine has poor oral bioavailability 
and generally will have less severe cardio -
vascular effects than pseudoephedrine.
• Pseudoephedrine indirectly stimulates 
alpha- and, to a lesser degree, beta-adrenergic 
receptors.
• Pseudoephedrine dosages >1 mg/kg can 
result in agitation, hyperactivity, and panting.
• Phenylephrine dosages >3–4 mg/kg may 
cause vomiting, lethargy or hyperactivity, 
hypertension, and tachycardia.
• Head-bobbing, DIC, or myoglobinuria 
indicate serious intoxication and a more 
  DIAGNOSIS
Other CNS stimulants and 
sympathomimetics—amphetamines, cocaine, serotonergic antidepressants, phenylprop -
anolamine, methylxanthines, ephedra.
• No specific clinical pathology alterations are 
expected in most cases.
• In severe cases DIC, myoglobinemia, 
myoglobinuria, or azotemia may occur.
Urine or serum from patients with pseudo -
ephedrine toxicosis may give a positive test 
for amphetamine in OTC drug test kits or 
human hospital drug screens.
  TREATMENT
• Manage severe or life-threatening signs first.
• Control CNS stimulation, then manage 
cardiovascular (CV) stimulation, as blood 
pressure and heart rate may decrease 
significantly once CNS signs are managed.
• For seizures, use propofol, pentobarbital, or 
phenobarbital; consider gas anesthetic for 
• For agitation, hyperactivity, or other CNS 
stimulation, use acepromazine or 
chlorpromazine.
• Cyproheptadine has been used with some 
success to manage dysphoria, vocalization, 
and hyperthermia.
• Propranolol (or other beta-blocker) may be 
considered in patients with sustained 
• External cooling measures may be required 
for hyperthermic patients.
• IV fluid administration assists in 
stabilization of CV effects, support of kidney 
function, and excretion of pseudoephedrine 
and its metabolites.
• Monitor heart rate/rhythm, body 
temperature, and blood pressure. In severely 
affected patients, monitor renal function, 
coagulation parameters, hydration, and 
• Gastrointestinal decontamination 
(induction of emesis, administration of 
activated charcoal) may be considered in 
patients that have ingested >1 mg/kg of 
pseudoephedrine and are not displaying 
significant clinical signs.
• Propofol 0.1–0.6 mg/kg/min IV.
• Pentobarbital 30 mg/kg IV to effect.
• Phenobarbital 3–4 mg/kg IV.• Acepromazine 0.05–1.0 mg/kg IM or IV; 
start low and titrate up as needed.
• Chlorpromazine 0.5–1.0 mg/kg IV or IM; 
• Cyproheptadine 1.1 mg/kg PO or per 
rectum q6h (dogs); 2–4 mg PO or per rectum 
(cats).
• Propranolol 0.02–0.06 mg/kg IV q6–8h 
PRN.
• Emetics—Dogs: 3% hydrogen peroxide 
2.2 mL/kg PO, maximum 45 mL, may repeat 
once if first dose unsuccessful; apomorphine 
crushed and diluted with sterile saline and 
instilled in conjunctival sac, rinse eye after 
emesis, or 0.03 mg/kg IV; ropinirole 
hydrochloride 3.75 mg/m2 as directed by 
product label. Cats: dexmedetomidine 6–18 
µg/kg IM; xylazine 0.44 mg/kg IM; 
hydromorphone 0.1 mg/kg SC.
• Activated charcoal 1–3 g/kg suspended in 
50–200 mL of water.
The use of diazepam to control CNS 
stimulation should be avoided, as diazepam 
may induce a dysphoric effect in these 
patients and worsen the CNS excitation.
  FOLLOW-UP
Renal insufficiency resulting from 
myoglobinuria may require long-term 
follow-up and care.
• CV = cardiovascular.
• OTC = over-the-counter.
Means C. Dietary supplements and herbs. In: 
Poppenga RH, Gwaltney-Brant SM, eds. 
Small Animal Toxicology Essentials. 
Chichester: Wiley-Blackwell, 2011, pp. 
161–169.
Means C. Ma huang: all natural but not 
always innocuous. Vet Med 1999, 
94:511–512.

Canine and Feline, Seventh Edition  1145
P
Pseudomacrothrombocytopenia (Inherited Macrothrombocytopenia)
  BASICS
OVERVIEW
• A common cause of thrombocytopenia and 
increased mean platelet volume (MPV) in 
cavalier King Charles spaniels (CKCS), and 
infrequently in other breeds.
• Caused by an inherited mutation that 
impairs platelet maturation, resulting in the 
early release of platelets from the bone 
marrow. The released platelets are significantly 
larger than normal.
• Overall platelet mass (product of platelet 
number and average size) is unaffected, 
therefore clinical signs of hypocoagulability 
are not seen.
• Dogs—primarily CKCS with infrequent 
reports in Norfolk terriers, Cairn terriers, 
English toy spaniels, and Jack Russell terriers; 
other breeds also sporadically affected.
• A similar condition is also reported in 
Akitas, although a specific mutation has not 
yet been identified in this breed.
• The condition is present from birth, but is 
often not detected until a CBC is performed. 
The mutation is autosomal, therefore there is 
no sex predilection.
SIGNS
Not associated with clinical signs; often 
incidentally noted on a CBC performed for 
other reasons.
• Caused by point mutations in the gene 
encoding β1-tubulin, which is involved in 
platelet formation. The mutations impair the 
formation of microtubules in the megakaryocyte 
(platelet precursor) and result in the release 
of lower numbers of platelets that are larger 
than normal.
• The condition is inherited in an autosomal 
fashion, with homozygotes exhibiting 
moderate to marked thrombocytopenia and 
moderate to marked increases in MPV. 
Heterozygotes are less severely affected and 
may have a mild thrombocytopenia and/or 
mild increase in MPV.
• In the United States, it has been estimated that 
approximately 47% of CKCS are homozygous 
for the mutation and 45% are heterozygous.
  DIAGNOSIS
• Must be differentiated from causes of 
pathologic thrombocytopenia such as 
immune-mediated thrombocytopenia, 
infectious diseases (especially tick-borne diseases), and causes of decreased platelet 
production (i.e., bone marrow disease).
• Breed (especially CKCS), absence of clinical 
signs, and a normal plateletcrit (PCT) (see 
CBC /Biochemistry/Urinalysis) are strongly 
suggestive of inherited macrothrombocytopenia.
• Blood smear evaluation is also 
recommended to rule out in vitro  platelet 
clumping, which artifactually induces a 
decreased platelet count and increased MPV.
• CBC—moderate to marked thrombo -
cytopenia (40,000–200,000/ μL) with 
significantly increased MPV; PCT expected 
to be within reference interval 
(RI = 0.129–0.403%).
• PCT—a numeric representation of overall 
platelet mass (product of platelet number and 
average size). Some automated analyzers 
calculate the value automatically. If not 
provided, PCT can be calculated using the 
following formula:
PCT = (PLT × MPV)/10,000
where PLT is platelet count and MPV is 
mean platelet volume.
If definitive diagnosis is desired, genetic 
testing to confirm the presence of the 
mutation can be performed; currently, this is 
available through the Auburn University 
Hemostasis Laboratory.
  TREATMENT
None required—nonpathogenic condition 
N/A
  FOLLOW-UP
Once affected individuals are identified, 
platelet mass in these patients should be 
evaluated via PCT; if this value falls below the 
reference interval, a concurrent pathologic 
thrombocytopenia may be present.
• CKCS = cavalier King Charles spaniel.
• MPV = mean platelet volume.
• PCT = plateletcrit.
• PLT = platelet count.INTERNET RESOURCES
https://www.vetmed.auburn.edu/academic-
departments/dept-of-pathobiology/
diagnostic-services/
Davis B, Toivio-Kinnucan M, Schuller S, 
Boudreaux MK. Mutation in beta1-tubulin 
correlates with macrothrombocytopenia in 
Cavalier King Charles Spaniels. J Vet Intern 
Med 2008, 22:540–545.
Author  Megan N. Caudill

1146  Blackwell’s Five-Minute Veterinary Consult  
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Ptyalism
  BASICS
• Excessive production and secretion of saliva 
(see Web Figure 1). • Pseudoptyalism is the 
excessive release of saliva that has accumulated 
in the oral cavity due to inability to swallow.
• Saliva is constantly produced and 
secreted into the oral cavity from the 
salivary glands. • Saliva production increases 
when salivary nuclei in the brainstem are 
stimulated. • Higher centers in the CNS can 
excite or inhibit salivary nuclei. • Taste and 
tactile stimuli in the oral cavity increase saliva 
production. • Physiologic hypersalivation 
may occur with: anticipation of eating, 
hyperthermia and purring (cats). • Saliva 
production may be increased with gastro­
intestinal (GI) or CNS disorders.
Skin—may cause salivary staining.
GENETICS
N/A
Variable
Worldwide
Species
• Congenital portosystemic shunts—
Yorkshire terrier, Maltese, Australian cattle 
dog, miniature schnauzer, and Irish 
wolfhound. • Congenital megaesophagus—
wirehaired fox terrier and miniature 
schnauzer; familial predispositions have been 
reported in German shepherd dog, 
Newfoundland, Great Dane, Irish setter, 
Chinese Shar ­Pei, greyhound, retriever 
breeds, and Siamese cats. • Congenital hiatal 
hernia—Chinese Shar ­Pei. • Lip 
conformation—giant breeds, such as Saint 
Bernard, Great Dane, and mastiff. 
• Brachycephalic airway syndrome—pug, 
English and French bulldog.
Young animals are more likely to have 
congenital abnormalities and to ingest foreign 
materials.
SIGNS
• Anorexia—with oral lesions, GI disease, and 
systemic disease. • Eating behavior changes—
with oral disease or cranial nerve (CN) 
dysfunction: may refuse hard food, chew only 
on the unaffected side (if unilateral lesion), 
maintain an unusual head/neck position, or drop food. • Other behavioral changes—
irritability, aggressiveness, and reclusiveness, 
especially if painful. • Dysphagia. • Nausea. 
• Regurgitation—with esophageal disease. 
• Vomiting—with GI or systemic disease. 
• Weight loss. • Pawing at the face or 
muzzle—with oral discomfort. • Neurologic 
signs—with exposure to caustic drugs or 
toxins, hepatic encephalopathy, seizure 
disorders or other intracranial disease.
• Periodontal disease. • Gingivitis/stomatitis—
with toxins, infection, immune ­mediated 
disease or nutritional deficiency. • Oral mass 
• Glossitis—with ulceration, mass or foreign 
body. • Oropharyngeal inflammation, 
ulceration, mass, or foreign body. • Blood in 
the saliva—with bleeding from the oral cavity, 
pharynx, or esophagus. • Halitosis—with oral 
disease (most common), or esophageal and 
gastric disease. • Facial pain. • Dysphagia. 
• CN deficits—trigeminal nerve (CN V) lesions 
can cause drooling due to inability to close the 
mouth; facial nerve palsy (CN VII) can cause 
drooling from the affected side; glossopharyngeal 
(CN IX), vagus (CN X), and hypoglossal (CN 
XII) nerve lesions can cause a loss of the gag 
reflex or inability to swallow. • Cheilitis or 
acne—persistent drooling can lead to 
dermatologic lesions.
CAUSES
Conformational Disorder of the Lips
Most common in giant ­breed dogs.
Oral and Pharyngeal
• Oral trauma. • Foreign body (e.g., stick, 
foxtail, or sewing needle). • Neoplasm. 
• Abscess. • Gingivitis or stomatitis—
secondary to periodontal disease, bacterial, 
viral (e.g., feline leukemia virus [FeLV] or 
feline immunodeficiency virus [FIV]) or fungal 
infection, immune ­mediated disease (e.g., 
lymphoplasmacytic stomatitis, pemphigus 
vulgaris), uremia, ingestion of a caustic agent, 
poisonous plants, effects of radiation therapy 
to the oral cavity or burns (e.g., biting on an 
electrical cord). • Swallowing disorders.
Salivary Gland
• Sialoadenitis. • Sialolithiasis. • Sialadenosis 
(idiopathic enlargement). • Mucocele. 
• Fistula. • Foreign body. • Neoplasm. 
• Infarct. • Immune ­mediated disease (rare).
Esophageal or GI
• Esophageal foreign body. • Esophageal 
neoplasm. • Esophageal stricture. 
• Esophagitis. • Gastroesophageal reflux 
disease (GERD). • Infection (e.g., 
spirocercosis, pythosis). • Hiatal hernia. 
• Megaesophagus. • Esophageal dysmotility. 
• Gastric distension/volvulus. • Gastric ulcer. 
• Gastroenteritis.
Metabolic
• Hepatic encephalopathy (especially in cats). 
• Hyperthermia. • Uremia.Neurologic
• Rabies—decreased swallowing causes 
increased drooling. • Pseudorabies in dogs. 
• Botulism. • Tetanus. • Dysautonomia. 
• Disorders causing dysphagia. • Disorders 
causing facial nerve palsy or a dropped jaw. 
• Seizures—during a seizure, ptyalism may 
occur because of autonomic discharge or 
reduced swallowing of saliva, and may be 
exacerbated by chomping of the jaws. • Nausea 
associated with vestibular disease. • Anxiety.
• Caustic substances (e.g., household cleaning 
products). • Anesthesia may induce reflux 
esophagitis. Drugs used for premedication may 
induce nausea, vomiting or ptyalism. • Oral, otic 
or ophthalmic medications that are poorly 
palatable (especially in cats). • Those that induce 
hypersalivation, including organophosphate 
compounds, cholinergic drugs, insecticides 
containing boric acid, pyrethrin and pyrethroid 
insecticides, ivermectin (dogs), fluids containing 
benzoic acid derivatives (cats), clozapine (a 
tricyclic dibenzodiazepine), caffeine, and illicit 
drugs such as amphetamines, cocaine, and 
opiates. Has also been reported with capromorelin 
administration in dogs and cats. • Animal venom 
(e.g., black widow spider, Gila monster, and 
North American scorpion). • Toad and newt 
secretions. • Plant consumption or prehension 
(e.g., poinsettia, Christmas trees, Amanita  
mushrooms) may cause increased salivation.
  DIAGNOSIS
• Differentiating causes of ptyalism and 
pseudoptyalism requires a thorough history, 
including vaccination status, current medications, 
possible toxin exposure, and duration of ptyalism. 
• May be able to distinguish salivation associated 
with nausea (signs of depression, lip smacking, 
and retching) from dysphagia by observing the 
patient. • Complete physical examination (with 
special attention to the oral cavity and neck) and 
neurologic examination are critical; wear 
examination gloves when rabies exposure is 
possible.
• CBC—often unremarkable; leukocytosis in 
patients with immune ­mediated, inflammatory 
or infectious disease. • Stress leukogram—
common in animals that have ingested a caustic 
agent or organophosphate. • FeLV ­infected cats 
may have leukopenia and nonregenerative 
anemia. • Serum creatine kinase activity should 
be evaluated in all dysphagic patients. • Possible 
microcytosis with portosystemic shunts. 
• Biochemical analysis—usually unremarkable 
except in patients with renal disease (azotemia, 
hyperphosphatemia), and hepatic encephalo­
pathy (possibly elevated hepatic enzyme 
activities, decreased BUN, hypoalbuminemia,

Canine and Feline, Seventh Edition  1147
P
hypocholesterolemia, hyperbilirubinemia, and 
hypoglycemia). • Marked ptyalism can result in 
hypokalemia and acidosis from the loss of 
potassium and bicarbonate ­rich saliva. 
• Urinalysis—often normal; decreased urine 
specific gravity with renal or hepatic disease. 
• Urate urolithiasis may be noted in patients 
with portosystemic shunts.
• Fasting and postprandial bile acids and/or 
fasting ammonia when hepatic encephalopathy 
is suspected. • Serologic FeLV and FIV testing 
in cats with oral lesions. • Acetylcholine 
receptor antibody titer if focal myasthenia 
gravis is suspected. • Serum cholinesterase level 
if organophosphate toxicosis is suspected. 
• Post­mortem fluorescent antibody testing of 
brain tissue if rabies is suspected.
IMAGING
• Survey radiography of the oral cavity, neck, 
and thorax when foreign body, structural 
abnormality, or neoplasm is suspected. 
• Abdominal radiographs ± abdominal 
ultrasound may help diagnose cause of 
vomiting; may also help diagnose hepatic or 
renal disease. • Ultrasonographic evaluation, 
CT angiography, portal venography, or portal 
scintigraphy may help diagnose a portosystemic 
shunt. • Fluoroscopic evaluation of swallowing 
may be useful in dysphagic patients to evaluate 
esophageal function and motility; use caution 
during barium administration in animals that 
are dysphagic. • MRI or CT for suspected 
intracranial lesions. • CT of head is more 
sensitive than radiographs, especially when 
foreign body or neoplasia is suspected.
• Biopsy and histopathology of mucocutaneous 
lesions—possibly including immunofluorescence 
testing when immune ­mediated disease (e.g., 
pemphigus vulgaris) is suspected. • Fine­needle 
aspiration of oral lesions and regional lymph 
nodes. • Biopsy and histopathology of oral 
lesion, salivary gland, or mass. • Consider 
esophagoscopy or gastroscopy if lesions distal to 
the oral cavity are suspected; endoscopic removal 
of foreign bodies may be possible.
Varies as to the underlying condition.
  TREATMENT
• T reat the underlying cause (refer to sections 
pertaining to specific conditions). 
• Symptomatic treatment to reduce the flow of 
saliva—generally unnecessary, may be of little 
value to the patient, and may mask other signs of 
the underlying cause and thus delay diagnosis; 
only recommended when hypersalivation is 
prolonged and severe and, if possible, after the 
underlying condition has been diagnosed.NURSING CARE
• Petroleum jelly can be applied to areas of 
the face constantly wet from saliva to help 
prevent moist dermatitis. • Astringent 
solutions applied for 10 minutes q8–12h can 
be used to treat areas of moist dermatitis.
ACTIVITY
N/A
DIET
• Enteral nutritional support (esophagostomy, 
gastrostomy tubes, etc.) may be needed in patients 
with ptyalism and anorexia secondary to severe 
oral, GI, or metabolic causes. • Reduced protein 
diets may be recommended for patients with 
hepatic encephalopathy, but are not necessarily 
warranted in animals with portosystemic shunts 
that are not encephalopathic.
Client education will depend on the 
• Surgical procedures will vary depending on 
underlying cause; ligation of parotid salivary 
duct has been described. • Corrective surgery 
for brachycephalic airway surgery may result 
in improved GI signs.
• Anticholinergic medications may be given 
symptomatically to reduce the flow of saliva; 
atropine 0.05 mg/kg SC PRN or glycopyrrolate 
0.01 mg/kg SC PRN. However, this is typically 
unnecessary as treatment should focus on 
underlying disease. • Antiemetics for nausea 
(see Acute Vomiting, for list of antiemetics and 
dosages). • Crystalloid fluids may be given IV 
or SC to treat dehydration caused by prolonged 
or severe ptyalism. • Antacid therapy may be 
useful for treatment of GERD (e.g., proton 
pump inhibitors—omeprazole 1 mg/kg PO 
q12h). • Phenobarbital 2 mg/kg PO q12h 
has been effective in treating idiopathic 
hypersialosis. • Anticonvulsant therapy is 
indicated for seizure activity.
N/A
• Some clinicians have anecdotally used 
levetiracetam for idiopathic hypersialosis. 
• Other acid ­reducing agents may be used.
  FOLLOW-UP
• Continually monitor hydration, body weight, serum electrolytes, and nutritional 
status, especially in dysphagic or anorexic 
animals.
• Metabolic acidosis. • Dehydration. 
• Hypokalemia. • Moist dermatitis. 
Depends on underlying cause. If underlying 
cause is correctable, prognosis for resolution 
may be more favorable.
N/A
Rabies
N/A
SYNONYMS
• Drooling. • Hypersalivation. • Sialism. 
• Sialorrhea. • Sialosis.
SEE ALSO
• Dysphagia. • Esophagitis. • Hepatic 
Encephalopathy. • Megaesophagus. 
• Periodontal Disease. • Stomatitis and Oral 
Ulceration.
• CN = cranial nerve. • FeLV = feline leukemia 
• GERD = gastroesophageal reflux disease. 
Claude AK, Dedeaux A, Chiavaccini L, 
Hinz S. Effects of maropitant citrate or 
acepromazine on the incidence of adverse 
effects associated with hydromorphone 
premedication in dogs. J Vet Intern Med 
2014, 8:1414–1417.
Kaye BM, Rutherford L, Perridge DJ, Haar 
GT. Relationship between brachycephalic 
airway syndrome and gastrointestinal signs 
in three breeds of dog. J Small Anim Pract 
2018, 59:670–673.
Niemiec BA. Ptyalism. In: Ettinger SJ, 
Elsevier, 2010, pp. 185–188.
van der Merwe LL, Christie J, Clift SJ, Dvir 
E. Salivary gland enlargement and 
sialorrhoea in dogs with spirocercosis: a 
retrospective and prospective study of 298 
cases. J S Afr Vet Assoc 2012, 83(1):920.
Author  Valerie J. Parker
Consulting Editor  Mark P . Rondeau(continued)  Ptyalism

1148  Blackwell’s Five-Minute Veterinary Consult  
P
Pulmonary Contusions
  BASICS
OVERVIEW
• Hemorrhage in the lung parenchyma 
caused by tearing and crushing from direct 
thoracic trauma. • Relatively small volumes 
of blood in the parenchyma markedly 
compromise lung function. • Fluid 
resuscitation for treatment of shock can 
exacerbate lung dysfunction from secondary 
edema.
SIGNS
• History of trauma. • Tachypnea. 
• Abnormal respiratory effort. • Postural 
adaptations to respiratory distress. • Cyanotic 
or pale mucous membranes. • Auscultation 
of harsh bronchovesicular sounds or crackles. 
• Expectoration of blood or blood-tinged 
fluid. • Additional injuries secondary to 
trauma and shock can also be noted.
• Blunt trauma. • Motor vehicle accidents. 
• Falls from a height. • Abuse.
  DIAGNOSIS
• Hemothorax—auscult dull lung sounds 
ventrally. • Pneumothorax—auscult dull 
lung sounds dorsally. • Diaphragmatic 
hernia—distinguished radiographically. 
• Coagulopathy can result in pulmonary 
hemorrhage; identified by abnormal 
coagulation tests or platelet count. • Acute 
onset of pulmonary hemorrhage—can be seen 
with neoplasia or pulmonary infarction from 
bacterial endocarditis or heartworm disease. 
• Expectoration of bloody fluid (not frank 
hemorrhage) can occur in animals with acute 
respiratory distress syndrome (ARDS) or 
congestive heart failure. • If no known history 
of trauma, pneumonia or edema (cardiogenic 
and noncardiogenic) are possible differentials.
• CBC—can reveal anemia or mature 
neutrophilia. • Biochemistry profile—can 
demonstrate hypoproteinemia (blood loss); 
can reveal damage to other organ systems.
IMAGING
• Usually a patchy alveolar pattern—focal or 
asymmetrical, but can be generalized. 
• Contusions generally worse in the area of 
rib fractures if present. • Always perform 
thoracic radiographs in trauma patients after 
stabilization to rule out hemothorax, 
pneumothorax, and diaphragmatic hernia.Thoracic Focused Assessment 
with Sonography for Trauma (TFAST®) 
and Focused Lung Ultrasound
• Point-of-care emergency ultrasound helps 
identify intrathoracic trauma during initial triage. 
• Increased lung rockets (B-lines) indicative of 
contusions or edema. • Absence of a glide sign 
dorsally indicative of pneumothorax. • Pleural 
effusion noted indicative of hemothorax.
• Coagulation tests for coagulopathy or 
disseminated intravascular coagulation. • Pulse 
oximetry or arterial blood gas analysis—can 
confirm hypoxemia. • Examination of tracheal 
wash cytology—can show excessive numbers of 
erythrocytes and macrophages.
  TREATMENT
• Usually inpatient for stabilization. • Support 
respiratory function, stabilize cardiovascular 
function. • If pneumothorax suspected, 
thoracocentesis should be performed. • Assess and 
treat injuries to other organ systems. • Restrict 
activity, minimize stress, and monitor carefully for 
deterioration. • Respiratory support—oxygen 
supplementation for hypoxemia; intubation and 
positive-pressure ventilation if severe. • Shock—
fluids generally required; judicious fluid therapy to 
avoid exacerbation of pulmonary edema. • Blood 
or plasma transfusion—consider if anemia or 
coagulopathy. • Nutritional support—as needed 
to maintain body condition and immune status.
• Oxygen supplementation if dyspnea 
or hypoxemia. • Analgesics administered 
as warranted. • Low-dose diuretics—
contraindicated unless suspected volume 
overload and respiratory distress is severe.
Diuretics—no value in the early stages of 
pulmonary contusions and potentially 
harmful; decrease intravascular volume, 
which is contraindicated for shock.
  FOLLOW-UP
membrane color, heart rate, pulse quality, and 
lung sounds. • Measure serial packed cell volume 
(PCV) and total solids and perform pulse oximetry 
and/or arterial blood gas analysis as needed for 
the first 24 hours. • Monitor ECG frequently 
to detect ventricular arrhythmias associated with hypoxemia or traumatic myocarditis. 
• Radiographs—repeated if clinically indicated.
Appropriate restriction of the animal to 
prevent trauma.
• Bacterial pneumonia (uncommon)—owing 
to systemic immunosuppression from trauma, 
shock, and reduced pulmonary defenses. 
• Development of a moist productive cough 
and failure to improve within 48 hours—
suspect pneumonia. • Patients with severe 
shock can develop ARDS (less common).
• Respiratory function can deteriorate during 
the initial 12–24 hours and then should 
gradually improve. • Clinical improvement 
within 48 hours with radiographic resolution 
likely in 7–10 days. • If patient fails to 
improve clinically after 48 hours, evaluate for 
complications or concurrent disease.
• Pneumothorax. • Fractured ribs. • Flail 
chest. • Ruptured trachea, bronchi, or 
esophagus. • Cardiac arrhythmias—ventricular. 
• Other possible complications of trauma.
SEE ALSO
Pneumothorax
• ARDS = acute respiratory distress 
syndrome. • PCV = packed cell volume. 
• TFAST® = Thoracic Focused Assessment 
with Sonography for T rauma.
Boysen SR, Lisciandro GR. The use of 
ultrasound for dogs and cats in the emergency 
room: AFAST and TFAST. Vet Clin North 
Am Small Anim Pract 2013, 43(4):773–797.
Campbell VL, King LG. Pulmonary function, 
ventilator management and outcome of 
dogs with thoracic trauma and pulmonary 
contusions: 10 cases (1994–1998). J Am 
Vet Med Assoc 2000, 217:1505–1509.
Holowaychuk MK, Marks SL, Hansen BG, 
DeFrancesco T. Pulmonary contusions. Stand 
Care Emerg Crit Care Med 2006, 8(10):1–6.
Powell LL, Rozanski EA, Tidwell AS, Rush 
JE. A retrospective analysis of pulmonary 
contusion secondary to motor vehicular 
accidents in 143 dogs: 1994–1997. J Vet 
Emerg Crit Care 1999, 9:127–136.
Vnuk D, Pirkic B, Maticic D, et al. Feline 
high-rise syndrome: 119 cases (1998–2001). 
J Feline Med Surg 2004, 6:5, 305–312.
Author  Cassandra O. Janson
acknowledge the prior contribution of Lesley 
G. King.

Canine and Feline, Seventh Edition  1149
P
Pulmonary Edema, Noncardiogenic
  BASICS
Accumulation of edema fluid in the 
pulmonary interstitium and alveoli, in the 
absence of heart disease.
• Associated with increased pulmonary 
vascular permeability and leakage of fluid into 
the interstitium and alveoli; if severe, can be 
accompanied by an inflammatory response 
and accumulation of neutrophils and 
macrophages. • Several mechanisms 
contribute to changes in pulmonary vascular 
permeability. • Stimulation of brainstem 
(medulla) vasomotor centers can lead to a 
reflex systemic release of catecholamines 
resulting in systemic vasoconstriction and 
temporary shunting of blood into the 
pulmonary circulation resulting in transient 
pulmonary circulatory overload and 
endothelial damage—likely pathogenesis in 
patients with neurogenic edema, 
electrocution, and upper airway obstruction. 
• In patients with upper airway obstruction, 
negative intrathoracic pressure from 
inspiratory attempts against an airway 
obstruction also contributes to edema 
formation. • Increased vascular permeability 
can be part of a generalized inflammatory 
response that develops in patients with 
systemic inflamm  atory response syndrome 
(SIRS), sepsis, or pancreatitis. • The inciting 
insult can trigger a cascade inflammatory 
response that often worsens over 24 hours 
following the initial episode. • Severity of 
clinical manifestation varies, ranging from 
mild to severe; the most seriously affected 
patients can progress from normal to death 
rapidly after the incident.
• Respiratory. • Cardiovascular—
hypotension, tachycardia, and shock. 
• Hemic/lymphatic/immune— 
if severe and causing respiratory failure, can 
be associated with disseminated intravascular 
coagulation (DIC). • Renal/urologic—acute 
renal failure.
GENETICS
Unknown
Uncommon
Species
None specific; brachycephalic dogs are more 
prone to airway obstruction, older large-breed 
dogs—laryngeal paralysis, small-breed dogs—
tracheal collapse.Mean Age and Range
• Higher incidence in pediatrics—associated 
with strangulation, head trauma, and electric 
cord bites. • Older—associated with laryngeal 
obstruction and neoplasia.
SIGNS
Vary, depending on underlying cause and 
severity.
• Predisposing causes—airway obstruction; 
electric cord bite; seizures; head trauma; near 
drowning; smoke exposure; adverse drug 
effects. • Acute onset of dyspnea.
• Mild to severe dyspnea. • Increased 
respiratory rate and effort; open-mouthed 
breathing. • Postural adaptations to 
respiratory distress (if severe)- orthopnea, 
unwillingness to lie down. • Pale or cyanotic 
mucous membranes (severe). • Harsh lung 
sounds (early, mild) or generalized crackles 
(late, severe) on auscultation. • Expectoration 
of pink froth or bubbles; can have large 
volumes of bloody fluid flowing out of 
endotracheal tube in severely affected 
intubated animals. • Normal cardiac 
auscultation; can detect arrhythmias; 
tachycardia common. • Oral ulceration or 
burns if electrocution. • Cranial nervous 
system abnormalities or other indications of 
neurologic disease. • Stridor over the upper 
airway in cases of brachycephalic syndrome, 
airway masses/abscesses, or foreign bodies. 
• Smokey odor or burns indicative of smoke 
exposure.
CAUSES
• Upper airway obstruction—laryngeal 
paralysis; choke-chain injury; mass; abscess. 
• Electrocution. • Acute neurologic disease—
head trauma; intra  -cranial hypertension, 
prolonged seizures. • Smoke inhalation. 
• Aspiration pneumonia. • Systemic 
inflammatory response syndrome—sepsis; 
endotoxemia; pancreatitis. • Anaphylaxis 
(cats). • Near drowning. • Adverse drug 
reactions including certain anesthetic drugs 
(ketamine), thiazides, or certain antineoplas-
tics (vincristine, cisplatin in cats). • T ransfusion-  
related acute lung injury—limited evidence in 
veterinary medicine. • Vasculitis.
• Hypoproteinemia. • Crystalloid fluid 
  DIAGNOSIS
• Cardiogenic pulmonary edema. 
• Pulmonary infection—bacterial, viral, or 
fungal pneumonia. • Pulmonary neoplasia. • Pulmonary hemorrhage (e.g., anticoagulant 
rodenticide exposure). • Pulmonary 
• Leukocytosis common, leukopenia and 
thrombocytopenia possible due to neutrophil 
sequestration in the lung and platelet 
consumption. • Biochemistries—usually 
normal; may note hypoalbuminemia owing 
to pulmonary protein loss; mild stress-related 
hyperglycemia. • Urinalysis—usually normal.
Coagulation testing—mild to moderate 
prolongation of prothrombin time/partial 
thromboplastin time (PT/PTT) in animals 
with consumption and DIC. Severe coagu-
lopathy may indicate hemorrhage as true 
cause for respiratory signs.
IMAGING
• Thoracic radiographs—vital; can reveal 
prominent interstitial pattern with mild or 
early disease; alveolar infiltrates with 
moderate or severe disease; infiltrates 
commonly but not always in dorsocaudal 
lung, sometimes asymmetrical and 
predominantly right-sided. Cardiac silhouette 
generally normal. • Echocardiography—rule 
out cardiogenic pulmonary edema. • Point-
of-care thoracic ultrasound—increased lung 
rockets (B-lines) may indicate pulmonary 
edema, increased left atrial:aortic ratio more 
indicative of cardiogenic edema and 
underlying heart disease.
• Cytology of airway fluid—inflammatory: 
neutrophils and some alveolar macrophages. 
Fluid tends to have high protein values >3 g/
dL. Culture negative unless concurrent 
bacterial pneumonia. • Edema fluid to 
plasma ratio (EF:PL) compares protein in the 
edema fluid to plasma protein. An increased 
ratio (>0.65) is indicative of noncardio  genic 
pulmonary edema. • Pulse oximetry—
noninvasive, continuous monitoring of 
arterial hemoglobin saturation with oxygen 
and arterial blood gas analysis. Demonstrates 
mild to severe hypoxemia and hypocapnia; 
not specific but indicates the severity of 
pulmonary dysfunction. • B-type natriuretic 
peptide (NT-proBNP) testing in cats and 
dogs can suggest underlying heart disease and 
supports a diagnosis of cardiogenic edema.
• Gross—lungs usually heavy, red, or congested; 
fail to collapse; often exhibit a wet cut surface; 
can ooze foam from major airways. 
• Histopathology—depends on severity of the 
insult; early, mild: may note eosinophilic 
amorphous material filling the alveoli or can be 
near normal because fluid removed in 
processing; severe: alveolar hyaline membranes, 
alveolitis, and interstitial inflammatory infiltrates 
with neutrophils and macrophages evident and

1150  Blackwell’s Five-Minute Veterinary Consult  
P
accompanied by atelectasis, vascular congestion, 
and hemorrhage; lesions can be found within 
hours of a severe insult.
  TREATMENT
• Inpatient vs. outpatient—depends on the 
severity of respiratory dysfunction and the 
underlying cause (e.g., airway obstruction or 
seizures generally require hospitalization). 
• Make every effort to resolve and treat the 
underlying cause. • Mild to moderate—
patients generally improve within 24–48 
hours; cardiovascular and respiratory support 
while the lung repairs. • Severe—difficult to 
treat; usually requires positive-pressure 
ventilation (PPV) due to respiratory failure; 
many patients die despite treatment.
• Oxygen therapy—vital in moderate to 
severe disease; administer via mask or hood, 
nasal catheter, or oxygen cage; inspired 
oxygen concentration depends on the severity 
of disease; most patients do well on 40–50% 
oxygen, but severe disease can require 
80–100% to maintain stability. • Severe—
can require PPV and positive end-expiratory 
pressure (PEEP). • Judicious fluid therapy 
with a balanced electrolyte solution as 
replacement solution for dehydration or 
shock; use cautious fluid administration and 
avoid fluid overload. • Plasma, albumin, or 
synthetic colloids—consider with severe 
hypoproteinemia or low colloid osmotic 
pressure; improved oncotic pressure may 
minimize movement of fluid into lungs.
ACTIVITY
Exercise restriction and minimal stress to 
decrease oxygen requirements.
• Warn client that the condition can worsen 
before improving. • Inform client that severe 
disease progressing rapidly to fulminant 
pulmonary edema and respiratory failure is 
associated with a very poor prognosis.
Relevant only for treating the underlying 
cause.
• Damaged endothelium in the pulmonary 
vasculature—no specific treatment available. 
• Inflammatory response—generated by a 
variety of mediators and cascades; cannot 
effectively be blocked by anti-inflammatory drugs. • Furosemide—diuresis not 
indicated as edema due to permeability 
changes, not high hydrostatic pressure. May 
act as bronchodilator and decrease 
pulmonary shunting, though evidence is 
limited. Can consider cautious boluses 
(0.5–2 mg/kg IV, IM) or nebulization, 
particularly early in course of disease. 
• Corticosteroids—for reduction of airway 
swelling in patients with upper airway 
obstruction; generally ineffective for 
pulmonary inflammatory response; if used, 
recommend anti-inflammatory dosage (e.g., 
dexamethasone SP at 0.05–0.1 mg/kg IV). 
• The use of beta-adrenergic agonists such 
as terbutaline may increase clearance of 
alveolar fluid. • Sedatives—use cautiously if 
anxiety is contributing to respiratory distress 
or airway obstruction. Sedation can decrease 
central respiratory drive, contributing to 
progression of respiratory failure. 
• Additional therapy as indicated by 
underlying cause—anticonvulsants, 
analgesia for oral ulcerations.
• Diuretics (e.g., furosemide)—can cause 
dehydration and decrease in intravascular 
volume, exacerbating cardiovascular collapse 
or shock with minimal effect on edema. 
• Corticosteroids—can predispose patients to 
infectious complications (e.g., pneumonia).
  FOLLOW-UP
• Monitor respiratory rate, pattern and 
auscultation (every 2–4 hours) for the first 
24–48 hours, depending on severity of 
disease. • Assess pulmonary function by pulse 
oximetry or arterial blood gas analysis 
(initially every 2–4 hours), depending on 
severity of disease. • Assess packed call 
volume (PCV) and total solids. Evaluate 
mucous membranes, pulse quality, heart rate, 
blood pressure, and urine output every 2–4 
hours to assess cardiovascular status and 
possible progression to shock.
• Avoid contact with electric wire. • Correct 
and avoid airway obstruction. • Manage 
seizures and neurologic disease.
Usually none if patient recovers from the 
acute crisis.
• Mild to moderate—resolution of signs in 
24–72 hours with supportive care. • Severe—
difficult to treat; can require PPV if 
respiratory failure. • Overall survival rates— 80–90%. • Long-term prognosis—excellent 
if responsive to therapy.
Acute respiratory distress syndrome.
SYNONYMS
• Acute alveolar failure. • Acute lung injury. 
• Capillary leak syndrome. • Congestive 
atelectasis. • Hemorrhagic lung syndrome. 
• Progressive respiratory distress. • Shock 
lung. • T raumatic wet lung.
SEE ALSO
Acute Respiratory Distress Syndrome.
• NT-ProBNP = B-type natriuretic peptide.
• PEEP = positive end-expiratory pressure.
• PPV = positive-pressure ventilation.
• PTT = partial thromboplastin time.
syndrome.
Drobatz KJ, Saunders HM, Pugh C, 
edema: 26 cases (1987–1993). J Am Vet 
Med Assoc 1995, 206:1732–1736.
Kerr LY. Pulmonary edema secondary to 
upper airway obstruction in the dog: A 
review of nine cases. J Am Anim Hosp 
Assoc 1989, 25:207–212.
and cats. J Am Anim Hosp Assoc 
1981,17:219–222.
Rozanski EA, Dhupa N, Rush JR, Murtaugh 
RJ. Differentiation of the etiology of 
pulmonary edema by measurement of the 
protein content. Proc Int Vet Emerg Crit 
Care Symp VI 1998:844.
Ward JL, Lisciandro GR, Ware WA, Viall AK, 
et al. Evaluation of point-of-care thoracic 
ultrasound and NT-proBNP for the 
diagnosis of congestive heart failure in cats 
with respiratory distress. J Vet Intern Med 
2018, 32:1530–1540.
Consulting Editors  Elizabeth Rozanski
G. King.Pulmonary Edema, Noncardiogenic  (continued)

Canine and Feline, Seventh Edition  1151
P
Pulmonary Thromboembolism
  BASICS
Develops when a thrombus lodges in the 
pulmonary arterial (PA) tree, occluding blood 
flow to the portion of lung supplied by that artery.
associated with heartworm disease (HWD) 
occurs in situ  in the pulmonary vessels; in most 
other instances, thrombus origin is unclear. 
• Potential sites of origin include right atrium, 
venae cavae, and jugular, femoral or mesenteric 
veins; thrombi are carried in the venous 
circulation to the lungs, and lodge in the 
pulmonary arteries. • Abnormal blood flow 
(stasis), vascular endothelial damage, and 
hypercoagulability are believed to predispose to 
thrombus formation. • Often a complication 
of another primary disease process.
• Cardiovascular—pulmonary hypertension 
(PH) may result, leading to right ventricular 
enlargement, right ventricular failure (cor 
pulmonale), and reduced cardiac output. 
• Respiratory—diminished pulmonary blood 
flow leads to arterial hypoxemia and dyspnea.
GENETICS
N/A
• Unknown—likelihood of PTE increases with 
abnormal coagulation or severe systemic 
disease. • Uncommon in the dog and cat; likely 
underdiagnosed due to nonspecific clinical 
signs, lack of clinical suspicion, and paucity of 
noninvasive, definitive diagnostic tests.
N/A
Species
N/A
• More frequently seen in middle-aged to 
older dogs. • Bimodal age distribution 
reported in cats; peak occurrence <4 years and 
>10 years of age.
N/A
SIGNS
• Often reflect the primary disease process. 
• May include peracute dyspnea, anorexia, 
syncope, collapse, cough, hemoptysis, 
weakness, exercise intolerance, and inability 
to sleep or get comfortable.
• Tachypnea and dyspnea in most animals; 
adventitious lung sounds in some animals. • Tachycardia, weak pulses, jugular vein 
distension, pale or cyanotic mucous membranes, 
delayed capillary refill time, right-sided heart 
murmur, and split or loud S2 in severe cases.
CAUSES
• HWD. • Neoplasia. 
• Hyperadrenocorticism (Cushing’s disease) 
or corticosteroid administration. • Protein-
losing nephropathy or enteropathy. 
(IMHA). • Pancreatitis. • Pulmonary 
hypertension (PH). • Orthopedic trauma or 
surgery. • Sepsis. • Disseminated intra -
vascular coagulation. • Liver disease.
• Coagulopathy, especially any hypercoagulable 
state. • Diseases listed under Causes are 
associated. • Estrogen administration, 
immobility, and air travel may be causative in 
humans.
  DIAGNOSIS
• Other diseases that cause clinically 
important dyspnea and hypoxemia without 
profound radiographic findings include upper 
airway obstruction, laryngeal paralysis, and 
diffuse airway disease processes (e.g., toxin 
inhalation and interstitial lung disease). 
• Upper airway obstruction often manifests 
as inspiratory dyspnea; breath sounds often 
loudest over trachea or larynx. • PTE should 
be a leading diagnostic consideration in a 
patient with acute onset of dyspnea or 
collapse and a known associated disease.
CBC—may be normal; thrombocytopenia 
may be seen in up to 50% of dogs with PTE; 
leukocytosis may develop. Biochemistry—
results often reflect underlying disease. 
Urinalysis—results often reflect underlying 
disease; evaluate for proteinuria.
• Arterial blood gases often show arterial 
hypoxemia ( Pao2 often <65 mmHg) and low 
Paco2 with respiratory alkalosis. • Metabolic 
and respiratory acidosis may develop in 
severely affected patients. • D-dimers result 
from the breakdown of crosslinked fibrin, 
indicate physiologic or pathologic thrombosis 
and testing plays a pivotal role in diagnostic 
algorithms for PTE in humans; however, 
utility for PTE diagnosis in veterinary 
patients is uncertain. • Thromboelastography 
provides a global assessment of coagulation 
and thrombolysis; may be useful in 
diagnosing systemic hypercoagulability but 
not widely available. • Coagulation profile 
may show high fibrin degradation products, 
abnormal fibrinogen, or alterations in one- 
stage prothrombin time (PT) and activated 
partial thromboplastin time (PTT). • Heartworm serology (antigen testing in 
dogs; antigen and antibody testing in cats) 
should be performed in any animal with 
suspected PTE. • Cardiac biomarkers—
cardiac troponin I and B-type natriuretic 
peptide (NT-proBNP) levels may be elevated.
IMAGING
• May be normal. • PA enlargement or 
pruning. • Cardiomegaly. • Interstitial and 
alveolar lung patterns. • Small-volume pleural 
effusion. • Areas of regional hyperlucency 
(Westermark sign).
• Right ventricular enlargement. • Enlarged 
PA segment. • Flattening of the 
interventricular septum. • Reduced left 
ventricular cavity size. • High-velocity 
tricuspid or pulmonic regurgitation jets 
provide evidence of PH in some patients. 
• Infrequently a thrombus is imaged in the 
right heart or the main PA segments.
CT, Angiography, and Radionuclide 
Studies
• One or more of these tests usually required 
for definitive diagnosis. • CT angiography is 
gold standard for the diagnosis of PTE. 
• Spiral CT nonselective angiography may 
show intraluminal filling defects created by 
emboli, peripheral wedge-shaped pulmonary 
infiltrates, or pleural effusion. • Right-sided 
cardiac catheterization with pulmonary 
angiography may permit identification of 
intraluminal filling defects or regions of 
reduced pulmonary blood flow. 
• Nonselective angiography using 
conventional radiographic techniques has a 
low level of diagnostic success. • Combined 
ventilation and perfusion scans with 
radioisotopes permit identification of 
well-ventilated lung regions that are not 
receiving normal blood flow.
ECG
• Acute cor pulmonale—right axis deviation, 
P pulmonale, ST segment deviation, large T 
waves. • Arrhythmias.
• Thrombi in major PA branches. • Some 
patients exhibit multiple smaller thrombi in 
small PA vessels, eventually leading to marked 
respiratory dysfunction and death. 
• Concurrent lung pathology (e.g., pneumonia, 
pulmonary edema, neoplasia, interstitial 
fibrosis) is common.
  TREATMENT
Hospitalize patients documented with PTE 
until hypoxemia is resolved.

1152  Blackwell’s Five-Minute Veterinary Consult  
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• Administer IV fluids cautiously unless 
preexisting volume depletion; they may 
precipitate right-sided congestive heart 
failure. • Administer oxygen if dyspneic and/
or Pao2 <65 mmHg; response to oxygen 
therapy is variable.
ACTIVITY
N/A
DIET
N/A
• Alert that condition is often fatal; further 
episodes likely unless an underlying cause is 
identified and corrected; sudden death is not 
unusual. • T raditional anticoagulants can lead to 
bleeding complications requiring frequent clotting 
time reevaluation (e.g., PT and PTT) for successful 
management; low-molecular-weight heparins 
(LMWHs) are safer and require less monitoring 
but are more expensive; anticoagulants may be 
required for several months, even after resolution 
of the causative disease.
N/A
• Always identify and treat underlying disease; if 
this is unlikely to be successful, aggressive efforts 
to treat PTE will probably be in vain. 
• Unfractionated heparin may help to prevent 
further thrombi from developing; low dosages are 
probably inadequate for initial management; a 
dosage of 200–300 units/kg SC q8h or 
alternatively a bolus of 200 units/kg IV followed 
by a CRI at 15–30 units/kg/h adjusted to 
maintain the PTT at 1.5–2 times the baseline 
value. • Thrombolytics (e.g., urokinase, 
streptokinase, or tissue plasminogen activator) 
may also be useful in hemodynamically unstable 
cases; these are expensive and carry a higher risk 
of bleeding complications. • Warfarin—may 
occasionally be considered for long-term 
treatment (0.1 mg/kg q24h), with dosage 
adjustments to maintain a PT 1.5–2 times the 
baseline value; animals must be heparinized prior 
to warfarin therapy to avoid initial hyper -
coagulable phase. • LMWHs are likely associated 
with fewer bleeding complications than 
unfractionated heparin or warfarin, require less 
intensive monitoring, and are more suitable for 
long-term management; however, their cost may 
be a limiting factor. • Thromboprophylactic 
effects have been demonstrated for dalteparin 
150 units/kg SC q12h in the absence of 
prolonged bleeding times or adverse effects; 
enoxaparin has been used at 1 mg/kg SC q12h. 
• Sildenafil 1–2 mg/kg PO q8h may help in 
some animals with PTE and concomitant PH.
N/APRECAUTIONS
Warfarin—interacts with many other drugs; 
degree of anticoagulation may change after 
giving these drugs, or with diet alterations. 
Dose titration may be difficult in patients with 
diseases that result in coagulopathy. Review 
mechanism of action and pharmacology of 
antithrombotic drugs before use.
See Precautions for warfarin.
N/A
  FOLLOW-UP
Serial arterial blood gases and/or pulse 
oximetry—may help determine improvement 
in respiratory function.
• Activity or physical therapy may improve 
venous blood flow and prevent development 
of venous thrombi in immobile patients with 
severe systemic disease. • Aspirin (0.5–5 mg/
kg PO q12–24h) may have some preventive 
role but is inadequate as treatment. 
• Clopidogrel (1–2 mg/kg PO q24h) is an 
alternative antiplatelet drug that may have 
some role in prevention. A single loading 
dose, up to 10 mg/kg, can be administered 
for rapid platelet inactivation in cases with 
active thrombosis. • Heparin may be 
administered to hospitalized animals 
predisposed to the development of PTE 
(200 units/kg IV initially and 75–200 units/
kg SC q8h). • Alternatively, dalteparin 
(150 units/kg SC q12h) or enoxaparin (1 mg/
kg SC q12h) may be used for thrombo -
prophylaxis. • Rivaroxaban, an oral factor Xa 
inhibitor, has been used in small animals 
(1 mg/kg PO q24h). Rivaroxaban and other 
newer oral antithrombotics, such as 
fondaparinux, apixaban, or dabigatran may 
be as effective as warfarin for prevention of 
recurrent thrombosis in people and require 
less monitoring; these drugs may play a future 
role in longer term anticoagulation of 
veterinary patients but further study on 
dosing and safety in animals is needed.
Bleeding complications may arise with 
anticoagulants. Bleeding may occur from any 
organ system. Anticipate active bleeding or 
anemia necessitating blood or plasma 
transfusion and have blood products readily 
Generally guarded to poor; depends on 
resolution of the precipitating cause. For 
irreversible diseases (e.g., some neoplasias and 
advanced protein-losing nephropathy), 
prognosis is poor; it is somewhat better for 
patients with PTE due to trauma or sepsis.  MISCELLANEOUS
• PH. • HWD. • IMHA. • Hyperadreno -
corticism. • Protein-losing nephropathy.
Predisposing conditions more likely in 
middle-aged and older animals.
N/A
N/A
SYNONYMS
Pulmonary embolism.
SEE ALSO
Cats.
Dogs.
• HWD = heartworm disease. 
• IMHA = immune-mediated hemolytic 
anemia. • LMWH = low-molecular-weight 
heparin. • NT-ProBNP = B-type natriuretic 
peptide. • PA = pulmonary artery/arterial. 
• PH = pulmonary hypertension. 
• PT = prothrombin time. 
• PTE = pulmonary thromboembolism. 
Goggs R, Blais MC, Brainard BM, et al. 
American College of Veterinary Emergency 
and Critical Care (ACVECC) Consensus on 
the Rational Use of Antithrombotics in 
Veterinary Critical Care (CURATIVE) 
guidelines: small animal. J Vet Emerg Crit 
Care 2019, 29:12–36.
Hackner SG. Pulmonary thromboembolism. 
MO: Saunders Elsevier, 2014, pp. 705–710.
Marschner CB, Kristensen AT, Rozanski EA. 
Diagnosis of canine pulmonary thromboem -
bolism by computed tomography and 
mathematical modelling using haemostatic and 
inflammatory variables. Vet J 2017, 229:6–12.
Schermerhorn T, Pembleton-Corbett JR, 
Kornreich B. Pulmonary thromboembolism 
in cats. J Vet Intern Med 2004, 18:533–535.
Authors  Suzanne M. Cunningham and John 
E. Rush
available onlinePulmonary Thromboembolism  (continued)

Canine and Feline, Seventh Edition  1153
P
  BASICS
Congenital narrowing of the right ventricular 
outflow tract, obstructing the passage of flow 
from the right ventricle (RV) to the 
pulmonary artery (PA); usually valvular, but 
may be subvalvular or supravalvular. Double- 
chambered RV is a variant of subvalvular 
pulmonic stenosis (PS) characterized by a 
focal muscular or fibromuscular stenosis in 
the mid RV.
The stenosis causes a pressure overload of the 
RV, resulting in concentric hypertrophy. The 
RV develops high systolic pressures to 
overcome the stenosis, whose magnitude 
correlates with the severity of the stenosis. 
The difference between the high right 
ventricular pressure and the normal PA 
pressure (i.e., the pressure gradient) is often 
used to describe the severity of the stenosis. 
Hypertrophy of the RV increases the risk of 
myocardial ischemia and arrhythmias. The 
geometric changes in the RV can result in 
secondary tricuspid insufficiency, although 
tricuspid insufficiency can also be associated 
with concurrent tricuspid dysplasia. Syncope 
can occur with exercise, as the RV may be 
unable to increase stroke volume adequately. 
T ricuspid insufficiency with or without 
myocardial failure of the RV can lead to high 
right atrial pressures and right-sided 
congestive heart failure (R-CHF). A 
concurrent atrial septal defect or patent 
foramen ovale can cause right-to-left 
shunting, especially with exercise, resulting in 
cyanosis on exertion. Mild PS usually 
produces no significant hemodynamic effects 
apart from an ejection murmur.
• Cardiovascular—R-CHF , arrhythmias.
• Hepatobiliary—hepatomegaly with 
R-CHF .
• Nervous—cerebral hypoperfusion during 
exercise.
GENETICS
Inherited defect in beagles; polygenic mode of 
transmission suggested.
• Most surveys show PS to be among the 
three most common congenital cardiac 
defects in dogs; comprising 21–32% of 
congenital heart defects.
• Uncommon in cats, especially as an isolated 
defect; comprised 3% of congenital heart 
defects in one study.
Species
English bulldog, Chihuahua, French bulldog, 
miniature schnauzer, West Highland white 
terrier, Samoyed, cocker spaniel, beagle, 
boxer, Pomeranian, German shepherd dog, 
whippet. Bulldog breeds are particularly 
predisposed to PS caused by anomalous 
coronary artery anatomy, where the left 
coronary artery originates from the same 
vessel as the right coronary, and causes 
stenosis as it wraps around the main PA.
Present from birth and may be detected as a 
murmur in puppies; if murmur is not detected, 
affected animals may not be identified until 
clinical signs develop later in life.
A predilection for males in English bulldogs 
and possibly other breeds.
SIGNS
• Mild stenosis—usually no clinical signs.
• Severely affected patients—may develop 
CHF , exertional syncope, or sudden death.
• Dyspnea.
• Exertional syncope, exercise intolerance, or 
• Systolic murmur loudest over the left heart 
base; may radiate widely but particularly 
dorsally on left.
• Murmur—midsystolic or holosystolic, and 
crescendo–decrescendo.
• Louder murmurs with a precordial thrill—
generally associated with more severe stenosis.
• Arrhythmias may occur; the heart rate may 
be high in CHF .
• Other signs of CHF include ascites, jugular 
venous distension, and tachypnea.
CAUSES
  DIAGNOSIS
• Similar murmurs may be found with: 
◦ Aortic stenosis. ◦ Ventricular or atrial 
septal defects with marked left-to-right 
shunting. ◦ Tetralogy of Fallot.
• R-CHF associated with a left-sided murmur 
may be seen with: ◦ Acquired valvular 
disease. ◦ Dilated cardiomyopathy.
• Polycythemia may be present with 
right-to-left shunting.• NT-proBNP is increased, particularly with 
severe stenosis or if clinical signs present.
IMAGING
• Thoracic radiographs usually show right- 
sided cardiac enlargement, with a post-
stenotic PA bulge visible on the dorsoventral 
view at 1–2 o’clock.
• The caudal vena cava may be wide, and 
ascites may be present with or without pleural 
effusion in congestive failure.
• Right ventricular hypertrophy, with 
flattening of the interventricular septum and 
a “figure-eight” appearance on short axis 
views in severe cases.
• Can usually image the site of the stenosis, 
but may be more difficult when the valve is 
hypoplastic; dysplastic pulmonic valves 
appear as thickened echodense leaflets; fused 
leaflets have abnormal motion with systolic 
doming; discrete subvalvular or supravalvular 
stenoses may appear as a localized hyper -
echoic narrowing.
• Post-stenotic dilation of the PA often 
present.
• Double-chambered RV can be difficult to 
image in conventional views.
• Localized hypertrophy may be seen in the 
right ventricular infundibular region.
• Anomalous coronary anatomy can be 
difficult to image.
Doppler Echocardiography
• Can use spectral Doppler to measure the 
elevated PA flow velocity to calculate the 
pressure gradient across the stenosis. Pressure 
gradients under 50 mmHg generally represent 
mild stenosis; those over 80 mmHg indicate 
severe stenosis.
• Color-flow Doppler may reveal tricuspid 
• Selective cardiac angiography can help 
identify the precise morphologic 
abnormalities prior to surgery; may image 
dysplastic valves and hypertrophy of the 
infundibulum more clearly.
• Useful in identifying PS caused by an 
anomalous coronary artery encircling the 
right ventricular outflow tract, which may 
affect the choice of therapy; recommended 
for bulldogs and brachycephalic breeds.
CT Angiography
Best technique to delineate coronary artery 
anomalies if resolution adequate and images 
are ECG-gated.
• QRS complex waveform changes include 
deep S waves in leads I, II, III, and aVF and 
right axis deviation.Pulmonic Stenosis

1154  Blackwell’s Five-Minute Veterinary Consult  
P
• Atrial fibrillation may occur with severe 
right atrial enlargement.
• Various forms exist; most result in right 
ventricular hypertrophy and post-stenotic 
dilation of the PA; infundibular hypertrophy 
may occur proximal to the obstruction.
• Hypoplastic pulmonic valve, with thickened 
leaflets (“dysplastic pulmonic valve”).
• Normal pulmonic valve annulus with fused 
commissures, often attached to vessel at 
supravalvular level.
• Anomalous coronary arteries.
• Discrete supravalvular or subvalvular stenosis, 
with possible concurrent tricuspid dysplasia.
• Fibromuscular bands dividing the right 
ventricular inflow and outflow tracts in 
double-chambered RV.
  TREATMENT
Most managed as outpatients.
Rarely, pleural effusions may need draining; 
ascites is usually treated medically.
ACTIVITY
Exercise should be restricted in cases with 
syncope or CHF , and severe exertion should 
be avoided in asymptomatic cases with severe 
stenosis.
DIET
Low-salt diets may benefit those with 
refractory ascites.
• Mildly affected animals may lead normal lives.
• Moderately and severely affected patients 
may benefit from interventions such as 
balloon catheter dilation or surgery; improved 
clinical signs and survival has been associated 
with successful balloon procedures.
• Prognosis is guarded once congestive signs 
develop.
• Balloon catheter dilation—relatively safe 
procedure that involves passing a catheter 
across the stenosis and inflating a balloon to 
dilate the obstruction; in many cases, the 
pressure gradient is significantly reduced, 
especially when the lesion is caused by fused 
commissures; less successful with dysplastic or 
hypoplastic valves and should be used with 
caution with anomalous coronary arteries.• Generally unsuccessful in double-
chambered RV.
• Stenting of the stenotic pulmonic valve has 
been described in cases where balloon 
valvuloplasty has been unsuccessful.
• Alternative surgical techniques include 
valvulotomy or patch-ventriculectomy 
procedures; mortality rates tend to be higher 
than with balloon valvuloplasty.
If signs of CHF , treat ascites with furosemide 
1–4 mg/kg PO q8–12h; in refractory failure, 
it is worth adding spironolactone 1–2 mg/kg 
PO q12h; aim should be to control CHF 
signs prior to catheter intervention.
Vasodilators (e.g., hydralazine) may cause 
hypotension without relieving the stenosis, 
positive inotropes may further increase 
myocardial oxygen consumption.
Avoid overuse of diuretics. angiotensin-
converting enzyme inhibitors may be helpful 
with congestive signs, but may cause 
hypotension. Start with low doses and 
monitor blood pressure.
  FOLLOW-UP
Use serial echocardiograms to follow the 
pressure gradient and cardiac chamber size.
• R-CHF .
• Exertional syncope.
• Mildly affected animals may remain 
asymptomatic with a normal lifespan.
• Severely affected animals have a guarded 
prognosis because they may develop CHF or 
sudden death; clinical signs are generally 
more common in animals >1 year of age.  MISCELLANEOUS
• Ventricular septal defects, atrial septal 
defects, and patent foramen ovale.
• English bulldogs described with a single 
right coronary artery from which an 
anomalous left main coronary artery arises 
and then encircles and constricts the base of 
the pulmonic valve; other coronary variations 
have also been described.
Defect and murmur are present from birth.
SYNONYMS
Pulmonary stenosis.
SEE ALSO
• ECG = electrocardiography.
• PS = pulmonic stenosis.
• R-CHF = right-sided congestive heart failure.
Fonfara S, Pereira YM, Swift S, et al. Balloon 
valvuloplasty for treatment of pulmonic 
stenosis in English bulldogs with an 
aberrant coronary artery. J Vet Intern Med 
2010, 24:354–359.
Francis AJ, Johnson MJS, Culshaw GC, et al. 
Outcome in 55 dogs with pulmonic stenosis 
that did not undergo balloon valvuloplasty 
or surgery. J Small Anim Pract 2011, 
52:282–288.
Locatelli C, Spalla I, Domenech O, et al. 
Pulmonic stenosis in dogs: survival and risk 
factors in a retrospective cohort of patients. 
J Small Anim Pract 2013, 54:445–452.
Oliveira P , Domenech O, Silva J, et al. 
Retrospective review of congenital heart 
disease in 976 dogs. J Vet Intern Med 2011, 
25:477–483.
Author  Virginia Luis Fuentes
available onlinePulmonic Stenosis  (continued)

Canine and Feline, Seventh Edition  1155
P
  BASICS
These problems include behaviors that are 
normal and common to most puppies but not 
acceptable to the family. They require some 
degree of modification by training and 
shaping to become acceptable. T raining and 
behavior issues include confinement training, 
housetraining, destructive chewing, play­
biting, jumping on people, and getting on 
counters or furniture.
GENETICS
• Activity levels and behaviors of young pups 
may be similar to those of their parents.
• Some problems may be more prevalent in 
breeds or lines with a high need for exercise 
and mental stimulation.
Common to almost all puppies.
N/A
Species
Dog.
Breeds selected for high ­energy, stamina, and 
working functions.
3–6 months of age but some dogs mature 
later and problems can persist into adulthood.
May be higher frequency in males.
SIGNS
Confinement Training
N/A
Housetraining
N/A
Playbiting
• The pet bites hands, legs, and/or clothing. 
Bites are usually inhibited but can cause 
injuries due to sharp teeth or insufficient bite 
inhibition.
• Growling and barking may be present but 
usually a higher pitch, with lower tones 
associated with social aggression.
• Attacks are usually triggered by movement 
or play with a family member but can be 
spontaneous.
Getting on Counters/Furniture
The pet gets on furniture and counters .
CAUSES
General
• Normal play and exploration.
• Inadequate supervision, training, socialization, or providing for mental 
stimulation or environmental enrichment.
• Owner responses may reinforce or 
exacerbate the behaviors.
A normal behavior, but rough play, teasing, 
and encouraging the pet to bite hands and 
feet may contribute to problems
• Insufficient outlets for normal play and 
exploration.
• Tempting objects or food left on counters/
furniture.
• Desire for social interaction.
• No acceptable alternative resting/bedding 
area.
  DIAGNOSIS
N/A (if distress or soiling during confinement 
rule out separation anxiety and barrier 
frustration).
N/A (rule out medical).
• Fear­related and defensive aggression—
aggression accompanied by signs of fear and/
or submission (lowered body, ears and tail 
down/tucked, horizontal retraction of oral 
commissures):
 ◦Occurs when the pet is in a situation 
perceived as threatening.
 ◦May be due to confrontation or 
punishment. Vocalization might include 
growling or yelping.
• Possessive aggression—occurs in situations 
in which there is competition for a resource:
 ◦Pet stiffens and hovers over the guarded 
object.
 ◦Increase in the speed of eating or quickly 
grasping an object tightly in the mouth may 
also be observed.
 ◦Growling has a deep tone.
 ◦Piloerection may occur, as might lunging, 
snapping, and biting.
• Reinforced aggression—the pet learns that 
aggressive behavior is effective at achieving 
goals (avoid being picked up, pushed off 
couch, restrained by collar, nails trimmed).
• Conflict ­related aggression—the pet bites in 
situations where it is frustrated or uncertain 
how to behave due to inconsistent responses 
by the family, including punishment.
• Medical, e.g., viral encephalitis, toxins, 
congenital disorders, usually accompanied by 
other signs of illness.Getting on Counters/Furniture
N/A
Housesoiling might require a urinalysis, fecal 
exam, or other tests as suggested by physical 
exam and history.
N/A except to rule out concurrent illness, 
e.g., hepatic shunt, CNS anomalies that affect 
learning.
  TREATMENT
N/A
ACTIVITY
Provide a regular daily routine of exercise, 
play, social interaction and mental 
DIET
Provide sufficient food to reduce the 
motivation to guard food.
General
• Constantly look for and reward acceptable 
• Avoid punishment, confrontation and 
corrections (e.g., striking, shaking the scruff, 
rolling on the back, or squeezing lips). These 
can worsen problems, negatively impact the 
bond with the pet, and lead to more serious 
problems, such as social fear and aggression).
• Teach the pet to sit or down using reward 
training. Direct him into the behavior prior 
to getting anything he wants or needs.
• Choose an appropriate confinement area. A 
crate is good for intermittent confinement but 
no longer than the pet can control urination 
and defecation (gradually increasing from 1 to 
5 hours). If the pet must be confined for 
longer a larger housing area should be 
provided with an elimination area within.
• Place treats, toys, or food in the area so that 
he is motivated to enter. For rest and sleep, 
place him in his confinement area. The pup 
should never be roughly forced in. A 
confinement area is for safety and comfort 
not punishment.
• Some degree of distress vocalization may 
occur the first few times the pup is confined. 
Music or talk radio may help to calm and 
mask environmental noises that trigger 
barking. A calming pheromone (Adaptil™) 
may help the puppy adapt. Avoid releasing 
the pup when he cries. Wait until he is quiet 
or squeak a toy from out of sight to get the 
pup to quiet before he is released.Puppy Behavior Problems

1156  Blackwell’s Five-Minute Veterinary Consult  
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• The puppy should be taken out to 
eliminate each hour when awake during the 
daytime when possible. If he does not 
eliminate within 10 minutes, return indoors, 
supervise closely for 15–30 minutes and try 
again. Take the pet out after play, exercise, 
naps, eating, drinking, or confinement, as 
well as prior to confinement, and whenever 
he exhibits preelimination circling and 
sniffing. Offer food 2–3 times daily at the 
same time to help establish an elimination 
routine.
• Until the puppy has completed 4 weeks 
without soiling, he should either be within 
eyesight or in his confinement area. A leash 
will help keep the pet close for supervision. 
Most pups can control elimination through 
the night by 3–4 months of age. By 4 
months, most puppies will have more of 
control during the daytime. Soiling can be 
prevented by closing doors or using barriers 
to limit access to areas.
• Do not punish. If caught in the act of soiling, 
calmly redirect the pup, and take outdoors. 
Elimination odors should be removed.
• If the pup eliminates in his crate—he may 
have been left there longer than he can 
control eliminating; the crate may be so large 
that he sleeps in one end and eliminates in 
the other; the puppy did not eliminate prior 
to confining; the meals were not matched to 
the elimination schedule; there is anxiety 
about confinement or being left alone (see 
Separation Anxiety Syndrome); there is an 
underlying medical cause.
• If it is not practical to take the pup outside 
frequently enough, he should be confined to 
a larger confinement area (e.g., pen) with an 
elimination pad within.
• Medical issues that may contribute to 
housetraining problems include problems 
that cause increased volume or frequency of 
elimination, and CNS problems that interfere 
with learning (hepatic encaphalopathy, 
hydrocephalus).
• Provide abundant opportunities for play/
exercise.
• Have toys available at all times to toss and 
distract the pet.
• Use treat ­ and kibble ­filled toys to keep the 
pet occupied and to provide outlets for 
exploration and scavenging.
• Use a leash attached to the supervised pup 
for more control.
• Confine the pup to his rest area when the 
family cannot effectively engage him in 
acceptable activities.
• Avoid games that encourage biting hands or 
feet.• Make all interactions structured and 
predictable by training the pet to sit before 
giving toys, food, play, and attention.
• Do not reinforce attention ­seeking behavior 
such as whining, barking, or pawing for 
attention.
• Say “Ouch” and immediately redirect or 
walk away to interrupt hard bites during play.
• Avoid physical corrections that can cause fear, 
anxiety, and aggression or stimulate the pup.
• Consider a head halter for head control of 
difficult pups.
• Enroll in puppy classes early (8–10 weeks 
of age).
• Keep appealing objects off counters and 
• Constantly supervise and monitor.
• Block access to problem areas.
• Confine the pup to his bed/rest area when 
he cannot be supervised.
• Provide interesting toys on the floor.
• Meet the pet’s needs for food, chewing, 
mental stimulation, and exploration.
Drugs are not indicated except for problems 
associated with anxiety.
Dog­appeasing pheromones, nutraceuticals 
such as alpha ­casozepine or l­theanine, or a 
calming probiotic may aid in stressful situations.
  FOLLOW-UP
• Phone follow ­ups at approximately 10 days, 
20 days, and 6 weeks following the initial visit 
are helpful.
• This can be done by a trained support staff 
member.
• Provide preventive counseling for all first 
puppy visits about normal behavior and 
behavioral needs (e.g., mental stimulation, 
socialization, exercise, object play).
• Discuss timing and use of rewards to teach 
what is desirable while behaviors that are 
undesirable should be prevented (supervision 
and confinement strategies) and not 
punished.
• Begin food ­lure reward training at 7–8 
weeks of age.• Make interactions predictable by teaching 
the pet to sit before giving anything of value.
• Enroll in a puppy class at 8–10 weeks of age.
• Provide regular sessions of physical exercise, 
mental stimulation including reward training, 
food puzzle toys, and safe items to explore 
and chew.
• Damage to household objects and clothing.
• Food stealing.
• Intestinal foreign bodies/obstructions.
• Injuries from playbites and jumping up.
• Owner frustration, weakened bond, and 
possible relinquishment.
• Prognosis is generally good.
• The frequency and intensity should 
decrease with age.
• Playbiting can usually be quickly managed 
if the family is consistent with training.
• Confinement training should take a few 
days to several weeks.
• Housetraining can be accomplished in a 
few weeks, but may take longer if the family 
is not consistent in supervision and training 
or the family schedule does not address the 
dog’s needs.
SEE ALSO
• Destructive Behavior—Dogs.
• Housesoiling—Dogs.
Dunbar I. Before and After Getting Your 
Puppy: The Positive Approach to Raising a 
Happy, Healthy, and Well ­Behaved Dog. San 
Francisco, CA: New World Library, 2004.
Landsberg GL, Hunthausen WL, Ackerman 
L. Handbook of Behavior Problems of the 
Elsevier Saunders, 2013.
McConnell PB, Scidmore B, The Puppy 
Primer, 2nd ed. Wenatchee, WA: 
McConnell Publishing, 2010.
Yin S. The Perfect Puppy in 7 days. Davis, 
CA: CattleDog Publishing, 2011.
Author  Wayne Hunthausen
available onlinePuppy Behavior Problems  (continued)

Canine and Feline, Seventh Edition  1157
P
  BASICS
OVERVIEW
future behavior, having lasting effects on 
cope in various environmental contexts.
• To grow up into a well-adjusted adult dog, 
adequate socialization and environmental 
exposure is needed during the socialization 
period and beyond into the first year of life.
• Socialization—a process of learning normal 
in various contexts.
• Socialization period—a sensitive window of 
development whereby a dog learns to 
communicate and relate to other dogs, 
humans, and the environment.
• Puppy classes—called socialization, 
preschool, or kindergarten classes. Allow dogs 
to socialize with other dogs, breeds, a variety 
of people and to be exposed to multiple and 
varied environmental stimuli in a positive and 
nonthreatening manner.
Species
Dogs
• Smaller breeds may mature faster and 
progress more quickly through windows of 
behavioral development.
• Amount of handling and exposure toward 
humans needed to reduce people-shyness may 
be genetically variable.
• The timing of first fear response is genetic -
ally variable, 39–55 days.
• The primary socialization period is between 
3 and 5 weeks. Puppies recognize kin and learn 
to relate and interact with other members of 
their species. The secondary socialization 
period occurs from 6 to 12 weeks, during this 
time most puppies are removed from its 
mother and littermates and raised with human 
caregivers. The ideal time for placement in a 
new home is probably after 7 or 8 weeks of age. 
• For puppy classes—healthy dewormed 
puppies should begin attending group 
socialization classes 10 days after receiving 
their first vaccine of their immunization 
series. Typical age at time of the first classes is 
between 8 and 12 weeks.
Male puppies play more than females.SIGNS
during sensitive periods of development.
• Dog-directed fear and/or aggression—lack 
of early familiarity and positive exposure 
results in fear and aggression or reactivity to 
unfamiliar dogs.
• Human-directed fear and/or aggression—
exposure with humans prior to 14 weeks is 
necessary, otherwise fear, avoidance, 
aggression, and behaving as if “feral.”
• Predatory aggression—social exposure, even 
to prey species, can reduce predatory behavior 
later in life.
• Reduced ability to copulate—in male dogs, 
lack of socialization toward conspecifics from 
3 weeks on results in the display of normal 
sexual behavior toward estrus females, but 
poor performance. In female dogs, timidity 
toward other dogs may preclude breeding.
• Fear and anxiety in unfamiliar environ -
ments with various sights, sounds, and smells.
• Attendance at group puppy classes during 
sensitive periods of development can prevent 
future behavior problems and/or allow for the 
early identification of abnormal and 
problematic behavior.
• Puppy socialization classes—age specific 
(to begin at 8–12 weeks) for group-controlled 
interactions. Focus is education on normal 
behavior, prevention of behavior problems, 
and addressing problem behaviors through 
management, supervision, and positive 
reinforcement training.
• Group classes of older puppies in their 
juvenile (3–6 months) and adolescent (6–18 
months) stages. Focus primarily on training 
manners, positive reinforcement training and 
teaching dogs to focus on their owners/handlers.
experiences prior to the completion of puppy 
behavior problems.
• Risk of contracting parvovirus was not 
increased when puppies attended well-run 
group socialization classes prior to completion 
of their vaccination series.
• Risks of exposure to infectious disease with 
socialization needs to be considered along 
with the risk of being undersocialized and 
not suitable as a pet because of fear, anxiety, 
and/or aggression.
• Along with a clean bill of health, initial 
least 1 week and preferably 10 days before 
puppy socialization classes start.
• Puppies should be dewormed according to 
the Companion Animal Parasite Council 
guidelines: https://capcvet.org/guidelines/
general-guidelines/
• Puppies should be free of clinical disease 
such as respiratory and gastrointestinal prior 
to each class.• Puppy socialization with people and dogs is 
only beneficial to behavioral development if 
the puppy finds human and/or dog contact 
enjoyable. Forced exposure, when it induces 
fear, is likely to exacerbate fear and/or 
• Experiences at the veterinary clinic should 
employ Fear Free ® and Low Stress techniques 
to prevent fear, anxiety, stress, and aggression 
during future veterinary visits.
• Overly shy, fearful, reactive or hyperactive 
puppies during routine veterinary health 
checks are likely to display the same behavior 
at 1 year of age.
• Puppies displaying fear and avoidance of 
being handled are likely to display fear and/or 
aggression with handling later in life.
• Excessive mouthing/biting or aggression 
over food resources at 8 weeks may indicate 
increased risk of aggression toward family 
members.
• Pet store puppies and those with early illness 
are more likely to develop behavior problems.
• T raumatic fear-inducing experiences, 
particularly during sensitive fear periods, 
between 8 and 10 weeks and between 6 and 
12 months (lasting up to 3 weeks), should be 
avoided.
• Removal from the mother and littermates 
prior to 6 weeks may increase the risk of 
separation anxiety and interdog aggression 
with poor interdog social skills.
• Avoiding exposure to other species during 
socialization can lead to fear or aggression 
towards the species.
• At the juvenile period, beginning at 3–4 
months of age, puppies may become less 
social and more fearful with increased 
independence seen in adolescence.
  DIAGNOSIS
• Identify abnormal and/or problematic 
schedule/refer for a behavior consultation.
• Behavioral manifestations of a lack of 
socialization may include: ◦ Global fears, 
encompassing fears of people, dogs, objects, 
sounds, and environments. ◦ Generalized 
anxiety and situational anxiety in unfamiliar 
environments. ◦ Specific fears, neophobia, 
and failure to habituate to novelty or stimuli. 
◦ Noise sensitivity, aversions, and phobias. 
◦ Hyperexcitability and hypervigilance with 
an inability to settle due to lack of early 
environmental enrichment. ◦ Aggression 
toward people and dogs in various contexts 
with various motivations (e.g., fear, predatory).
Indicated when considering behavioral 
medications.Puppy Socialization and Puppy Classes

1158  Blackwell’s Five-Minute Veterinary Consult  
P
  TREATMENT
• Attendance at group puppy socialization 
classes and social exposure is recommended 
for all healthy puppies prior to 16 weeks of 
age and prior to being fully vaccinated.
• Socialization “vaccinates” against the 
development of future behavioral problems 
and it should begin concurrently with the 
puppy immunization series.
• Food treats should be used liberally with 
new and repeated socialization experiences.
encouraged using toys.
• Healthy puppies usually have voracious 
appetites. If the puppy is not consuming food 
treats, it suggests the puppy is fearful and the 
experience is not beneficial for socialization.
• Healthy and well-adjusted puppies play. If 
the puppy will not engage in play it suggests 
the puppy is fearful and the experience is not 
beneficial for socialization.
birth, and include exposure to various smells 
and different surfaces with mild fluctuations 
in temperature.
the puppy to choose to interact and make 
treats: ◦ Meet people of different ages, 
stature, gait, and complexion. ◦ Meet 
friendly dogs of different breeds. ◦ Meet 
other pets in the home (such as cats).
Recommendations for Puppy 
Socialization Classes
• All healthy puppies, between 8 and 12 
weeks of age should be enrolled into group 
puppy socialization classes.
• Puppies attending are deemed healthy by a 
veterinary examination, free from clinical 
signs (e.g., coughing, diarrhea), have been 
dewormed, and have started their vaccination 
series.
• Classes are attended by puppies and their 
owners at least weekly and are typically about 
an hour in length.
• Rotating classes should cover the following 
monitored off-leash play (5–10 minutes) with 
other puppies in a secure environment, 
typically at the start and end of class. ◦ Health 
and handling—instruction and positive 
grooming facility, and at home. ◦ Sights and 
sounds—exposure to novel environments, 
objects, surfaces, and sounds. Attending people have opportunities for interacting with puppies 
in a positive manner. ◦ Rearing advice—
education on normal dog body language, 
learning, behavior problem-solving/prevention, 
and puppy raising. ◦ Basic manners—positive 
reinforcement training to address mouthing/
biting, jumping, chewing, stealing objects, 
food bowl safety, confinement training, leash 
manners, and house training. ◦ Puppy classes 
offered at the veterinary hospital can also help 
to insure a focus on positive exposures to the 
veterinary facility, equipment, and procedures.
• Selective serotonin reuptake inhibitors and 
tricyclic antidepressants may be indicated for 
the treatment of fear, anxiety, and aggression-
related problems when combined with 
behavior and environmental modification.
• May “in effect” chemically place the puppy 
back into a socialization state and aid 
socialization experiences.
• Consider daily or situational behavior 
medications based on the underlying 
condition; for dogs, 12 weeks or greater, who 
demonstrate abnormal fear, anxiety, 
aggression or reactivity.
• Alpha-casozepine, a bovine-sourced hydrolyzed 
milk protein may have calming properties.
• l-Theanine, an extract found in green tea, 
may reduce fear, anxiety, and stress.
• Calming Care (Purina ®) probiotic may help 
to maintain calm behavior.
Adaptil (CEVA), a synthetic dog-appeasing 
pheromone, may improve socialization 
experiences and facilitate adaptation to new 
  FOLLOW-UP
Question owners about behavior problems 
routinely and encourage concerns regarding 
problematic behavior to be brought to their 
veterinarian’s attention as soon as possible.PREVENTION/AVOIDANCE
• Preventive counseling at the first puppy 
visit reduces risk of housesoiling, mounting, 
excess play, mouthing of people, demanding 
food, and fear of unfamiliar people.
• Prevention of problems is preferable and 
easier than treatment.
• Socialization experiences must be 
positive for the puppy to benefit from the 
experiences.
• Negative social and environmental 
experiences can sensitize the puppy as it is 
difficult to habituate to stimuli that induce 
• Puppies raised in suboptimal environments 
may be resistant to socialization.
that the exposure is not positive for the 
puppy.
Early identification and intervention gives 
the best prognostic outcome and chance 
for cure.
anxiety, and aggression.
• www.avsab.org
• www.dacvb.org
• www.fearfreepets.com
• www.puppystartright.com
• https://karenpryoracademy.com/courses/
puppy-start-right/
Martin KM, Martin D. Puppy Start Right: 
Foundation T raining for the Companion 
Dog. Waltham, MA: Sunshine Books, 2011.
Shaw JK, Martin D. Canine And Feline 
Behavior For Veterinary Technicians 
And Nurses. Ames, IA: John Wiley &  
Sons, 2015.
Zulch H, Mills DS. Life Skills For Puppies. 
Poundbury, UK: Hubble & Hattie, 2012.
Authors  Kenneth M. Martin and Debbie 
Martin
Consulting Editor  Gary M. LandsbergPuppy Socialization and Puppy Classes  (continued)

Canine and Feline, Seventh Edition  1159
P  BASICS
OVERVIEW
• Uncommon granulomatous and pustular 
disorder of puppies.
• Rarely seen in adult dogs.
• Affects primarily the face, pinnae, and 
submandibular lymph nodes.
• Immunopathogenesis unknown.
• Dogs.
• Age range—usually between 3 weeks and 4 
months.
• Predisposed breeds—golden retriever, 
Labrador retriever, dachshund, and Gordon 
setter.
SIGNS
• Acutely swollen face (eyelids, lips, and 
muzzle).
• Submandibular lymphadenopathy.
• Marked pustular and exudative dermatitis; 
frequently fistulates; develops within 24–48 
hours.
• Purulent otitis externa.
• Lesions often become crusted.
• Affected skin is usually painful.
• Lethargy—50% of cases.
• Anorexia, pyrexia, and sterile suppurative 
arthritis—25% of cases.
• Sterile pyogranulomatous panniculitis (rare) 
over the trunk, preputial, or perianal area; 
lesions may appear as fluctuant subcutaneous 
nodules that fistulate.
Unknown—an immune dysfunction with a 
heritable cause is suspected.
  DIAGNOSIS
• Bacterial folliculitis/furunculosis.
• Drug reaction/eruption.
• Deep fungal infection.
• Cutaneous hypersensitivity.
• Vaccination reaction.
• Hymenoptera or insect envenomation.
• Acute lymphoma.
• Cytology—pyogranulomatous 
inflammation with no microorganisms; 
nondegenerate neutrophils.
• Culture—often sterile in early cases; 
secondary infection with chronicity.
Skin biopsy.PATHOLOGIC FINDINGS
• Multiple discrete or confluent granulomas 
and pyogranulomas—clusters of large 
epithelioid macrophages and neutrophils.
• Sebaceous glands and apocrine glands may 
be obliterated.
• Suppurative changes in the dermis—
predominate in later stages.
• Panniculitis.
• Exudate culture—important for selection 
of antibiotics if secondary infection  
  TREATMENT
• Early and aggressive therapy necessary 
because scarring may be severe.
• Topical therapy—may be soothing and 
palliative; adjunct to corticosteroids.
• Corticosteroids—high doses required; 
prednisolone 2.2 mg/kg divided q12h for at 
least 2 weeks then decreased over 2–4 weeks 
or dexamethasone 0.2 mg/kg q24h.
• Do not taper too rapidly.
• Corticosteroid—resistant cases: cyclosporine 
5 mg/kg q24h.
• Adult dogs with panniculitis may require 
longer therapy.
• Antibiotics—only if there is evidence of 
secondary bacterial infection or as an adjunct 
therapy with immunosuppressive doses of 
  FOLLOW-UP
• Most cases do not recur.
• Scarring may persist, especially around 
the eyes.
SYNONYMS
• Juvenile pyoderma.
• Juvenile sterile granulomatous dermatitis 
and lymphadenitis. Suggested Reading
Albanese F . Canine and Feline Skin Cytology: 
a Comprehensive and Illustrated Guide to 
the Interpretation of Skin Lesions via 
Cytological Examination. Switzerland, 
Springer International, 2017.
2013, pp. 708–709.
Harvey RG. Skin Diseases of the Dog 
and Cat, 3rd ed. London UK; CRC Press, 
2018.
Resnick
Helton Rhodes.Puppy Strangles (Juvenile Cellulitis)

1160  Blackwell’s Five-Minute Veterinary Consult  
P  BASICS
Microbial colonization of the upper urinary 
tract, including the renal pelvis, collecting 
diverticula, renal parenchyma, and ureters; 
because it is not usually limited to the renal 
pelvis and parenchyma, a more descriptive term 
is upper urinary tract infection (UTI); this 
chapter is limited to bacterial pyelonephritis.
• Infection of any portion of the urinary tract 
usually requires impairment of normal host 
defenses against UTI (see Lower Urinary T ract 
Infection chapters); normal defenses against 
ascending UTI include mucosal defense barriers, 
ureteral peristalsis, ureterovesical flap valves, 
unidirectional flow of urine, and an extensive 
renal blood supply. Pyelonephritis usually occurs 
by ascension of microbes causing lower UTI. 
Hematogenous seeding of the kidneys is an 
uncommon cause of pyelonephritis. Regardless 
of the route of infection, an upper UTI is 
frequently accompanied by lower UTI.
• Pyelonephritis can develop secondarily to 
infected nephroliths. Upper UTI with 
urease-producing bacteria can predispose to 
struvite nephroliths (see Urolithiasis, 
Struvite—Dogs).
• Obstruction of an infected kidney or ureter 
can rapidly cause septicemia (urosepsis).
• Can cause urosepsis, thus affecting any 
body system.
• Unknown.
• Probably occurs more commonly than is 
recognized clinically, because many animals 
with pyelonephritis are asymptomatic or have 
signs limited to lower UTI.
Species
Detected more frequently in dog than cat.
• Dogs of any age can be affected.
• Cats—UTI is uncommon in young to 
middle-age cats. UTI is more common in cats 
UTI affects females more commonly than 
males.
SIGNS
Differentiation between pyelonephritis, 
subclinical bacteriuria, and lower UTI may be 
difficult in some patients.
• Polyuria/polydipsia.• Abdominal or lumbar pain (uncommon).
• Signs associated with lower UTI may 
predominate—e.g., dysuria, pollakiuria, 
periuria, stranguria, hematuria, and 
malodorous or discolored urine.
• Signs attributable to chronic kidney disease 
(CKD)—e.g., polyuria/polydipsia, anorexia, 
vomiting, diarrhea, lethargy.
• May lack specific signs related to upper UTI.
• Fever.
• Pain upon palpation of kidneys.
• One or both kidneys may be reduced in 
size with chronic pyelonephritis, or kidneys 
may be increased in size with acute pyelo  - 
nephritis.
CAUSES
Usually, ascending UTI caused by aerobic 
bacteria; most common isolates are 
Escherichia coli  and Staphylococcus  spp.; other 
bacteria, including Proteus , Streptococcus , 
Klebsiella , Enterobacter , and Pseudomonas  spp., 
which frequently infect the lower urinary 
tract, may ascend into the upper urinary 
tract. Anaerobic bacteria, ureaplasma, and 
fungi uncommonly infect the upper urinary 
tract.
• Ectopic ureters, vesicoureteral reflux, 
congenital renal dysplasia, and lower UTI.
• Conditions that predispose to bacteriuria—
e.g., diabetes mellitus, hyperadrenocorticism, 
exogenous steroid administration, CKD, 
indwelling urinary catheters, urine retention, 
uroliths, urinary tract neoplasia, perineal 
  DIAGNOSIS
• Clinical diagnosis of pyelonephritis is 
usually presumptive, based on results from 
CBC, biochemical analysis, urinalysis, urine 
culture, and diagnostic imaging; definitive 
diagnosis is not usually required for planning 
• Since many lack specific symptoms 
attributable to pyelonephritis, any patient 
with UTI could potentially have pyelo -
nephritis; the best methods for differentiating 
between upper and lower UTI are 
ultrasonography or excretory urography.
• Consider pyelonephritis as a rule-out for 
fever of unknown origin, polyuria/polydipsia, 
acute decline in renal function, and/or 
lumbar/abdominal pain.
• CBC—results often normal with chronic 
pyelonephritis; leukocytosis and immature 
neutrophilia may be detected in some 
patients.• Biochemistry—values usually normal 
unless chronic pyelonephritis leads to CKD 
(azotemia with inappropriate urine specific 
gravity).
proteinuria, bacteriuria, and leukocyte casts. 
Leukocyte casts are diagnostic for renal 
inflammation, but unfortunately are very 
uncommon. Observe dilute urine specific 
gravity in patients with nephrogenic diabetes 
insipidus, which may occur secondary to 
pyelonephritis from Gram-negative bacteria. 
Absence of these abnormalities does not rule 
out pyelonephritis.
• Quantitative urine culture to confirm UTI; 
see Lower Urinary T ract Infection chapters for 
• Dogs with chronic pyelonephritis may have 
a negative urine culture and may require 
multiple urine cultures to confirm UTI.
IMAGING
• Ultrasonography and excretory urography 
are the best methods for presumptively 
differentiating between upper and lower UTI. 
Ultrasonography is more sensitive than 
excretory urography for identification of 
mild-to-moderate acute pyelonephritis.
• Ultrasonographic findings supporting 
pyelonephritis include dilation of the renal 
pelvis and proximal ureter and a hyperechoic 
mucosal margin line within the renal pelvis 
and/or proximal ureter.
• IV urography may reveal decreased opacity 
of the nephrogram phase, dilation and 
blunting of the renal pelvis with lack of 
filling of the collecting diverticula, decreased 
opacity of contrast media in the collecting 
system, and dilation of the proximal ureter.
• In patients with acute pyelonephritis, the 
kidneys may be large; in patients with chronic 
pyelonephritis, the kidneys may be small, 
with an irregular surface contour.
• Concomitant nephroliths detected in some 
patients by survey radiography or ultrasono- 
graphy.
Definitive diagnosis requires urine cultures 
obtained from the renal pelvis. Pyelocentesis 
can be performed percutaneously using 
ultrasound guidance or during exploratory 
surgery. Urine cultures from the renal pelvis 
usually are similar to cultures from the 
bladder unless obstruction is present.
• Kidneys affected by chronic pyelonephritis 
may have areas of infarction and scarring on 
the capsular surface. The renal pelvis and 
collecting diverticula may be dilated and 
distorted from chronic infection and 
inflammation. Purulent exudate is 
occasionally observed in the renal pelvis.Pyelonephritis

Canine and Feline, Seventh Edition  1161
P• Light microscopic findings include 
papillitis, pyelitis, interstitial nephritis, and 
leukocyte casts in tubular lumens.
  TREATMENT
Outpatient treatment with oral antibiotics if 
the animal is clinically well. Hospitalized care 
if patient is dehydrated, has decreased renal 
function or if sepsis is suspected.
ACTIVITY
Unlimited
DIET
Renal therapeutic diets are recommended for 
• Recurrent pyelonephritis may be asympt -
omatic. Unresolved chronic pyelonephritis may 
lead to progression of CKD; diagnostic 
follow-up is important to document resolution 
or progression of pyelonephritis.
• In patients with infected nephroliths, 
resolution of pyelonephritis is unlikely unless 
the nephroliths are removed.
• Complete obstruction of the upper urinary 
tract of a patient with pyelonephritis may 
rapidly progress to septicemia and therefore 
should be regarded as a medical emergency. The 
cause of the obstruction should be corrected by 
endoscopic or surgical ureteral stent placement.
• Infected nephroliths—remove surgically, 
medically dissolve (struvite), or fragment by 
extracorporeal shock wave lithotripsy; use 
periprocedural antibiotics to reduce the risk 
of urosepsis when manipulating infected 
nephroliths.
• Unilateral nephrectomy is usually not 
effective for elimination of suspected 
unilateral pyelonephritis.
• Base antibiotic selection on urine culture 
and susceptibility testing. Initiate antibiotics 
pending culture results.
• Antibiotics should be bactericidal, achieve 
good serum and urine concentrations, and 
not be nephrotoxic.• High serum and urinary antibiotic 
concentrations do not necessarily ensure high 
tissue concentrations in the renal medulla; 
thus, chronic pyelonephritis may be difficult 
to eradicate.
• If systemically ill or azotemic, administer 
IV antibiotics for initial 48 hours.
• Give orally administered antibiotics at full 
therapeutic dosages for 2–6 weeks. Duration 
of antibiotics required for resolution of 
pyelonephritis is not definitively known.
• Do not use drugs that achieve good 
concentrations in urine but poor concen -
trations in serum (e.g., nitrofurantoin).
Do not use aminoglycosides unless no other 
alternatives exist on the basis of urine culture 
and susceptibility testing.
T rimethoprim-sulfa combinations can cause 
side effects (keratoconjunctivitis sicca, blood 
dyscrasias, and polyarthritis) when administered 
for more than 4 weeks.
  FOLLOW-UP
Perform urine cultures and urinalysis during 
antibiotic administration ( ∼5–7 days into 
treatment) and 1 and 4 weeks after antibiotics 
are finished.
Eliminate factors predisposing to UTI; 
correct ectopic ureters.
Progressive CKD, recurrent pyelonephritis, 
struvite nephroliths, septicemia, septic shock, 
metastatic infection (e.g., endocarditis, 
polyarthritis).
• Patients with acute or subacute pyelo -
nephritis—fair to good, with a return 
to normal health unless the patient also 
has nephroliths, CKD, or some other 
underlying cause for UTI (e.g., obstruction 
or neoplasia).
• Established chronic infection of the renal 
medulla may be difficult to resolve because of 
poor tissue penetration of antibiotics.
• Patients with CKD caused by pyelo -
nephritis—prognosis determined by the 
severity and rate of progression of the CKD.• Recurrent pyelonephritis is likely if infected 
nephroliths are not removed.
Hyperadrenocorticism, exogenous 
glucocorticoid administration, CKD, 
hyperthyroidism (cats), and diabetes mellitus 
are associated with lower UTI, which can 
ascend into the ureters and kidneys.
Use antibiotics that are safe for the pregnant 
bitch or queen.
SYNONYMS
Upper UTI, pyelitis.
SEE ALSO
Bouillon J, Snead E, Casswell J, et al. 
Pyelonephritis in dogs: retrospective study 
of 47 histologically diagnosed cases 
(2005–2015). J Vet Intern Med 2018, 
32:249–259.
Etedali NM, Reetz JA, Foster JD. 
Complications and clinical utility of 
ultrasonographically guided pyelocentesis 
and antegrade pyelography in cats and dogs: 
49 cases (2007–2015). J Am Vet Med Assoc 
2019, 254:826–834.
Foster JD, Krishnan H, Cole S. 
Characterization of subclinical bacteriuria, 
bacterial cystitis and pyelonephritis in dogs 
with chronic kidney disease. J Am Vet Med 
Assoc 2018, 252:1257–1262.
available online(continued)  Pyelonephritis

1162  Blackwell’s Five-Minute Veterinary Consult  
P  BASICS
• Bacterial infection of the skin.
• Surface bacterial infections—often referred 
to as a “hot spot;” represents an acute moist 
dermatitis involving the surface of the skin.
• Superficial pyoderma—involves the 
epidermis and the intact hair follicle; includes 
mucocutaneous pyoderma.
• Deep pyoderma—involves the dermis and 
possibly subcutis; furunculosis is often 
present; patients can be systemically ill.
• Skin infections occur when the surface 
barrier of the skin has been broken, the skin 
has become macerated by chronic exposure to 
moisture, the population of resident bacterial 
flora has been altered, circulation has been 
impaired, and/or immunocompetency of the 
patient has been negatively impacted by 
systemic illness or immunosuppressive therapy.
• Pyoderma is usually secondary to an 
underlying cause; the primary, underlying 
cause should be identified and managed to 
reduce the frequency and recurrence of skin 
GENETICS
N/A
• Dogs—very common.
• Cats—uncommon.
Species
• Dog—short-coated breeds, especially those 
with excessive skin folds.
• German shepherd dog—severe, inflamm -
atory and deep pyoderma that responds to 
antibiotics; frequently relapses.
Age of onset is usually directly related to the 
None
SIGNS
• Superficial—usually involves the trunk; 
extent of lesions may be obscured by hair coat.
• Deep—often affects the chin, dorsal 
muzzle, pressure points, and feet; may be 
generalized and associated with symptoms of 
systemic illness, such as pyrexia and/or pain.
• Acute or gradual onset.• Variable pruritus—typically pruritic; the 
underlying cause may be pruritic or the 
staphylococcal infection itself may be pruritic; 
may not be pruritic if associated with hyper  - 
• Papules.
• Pustules.
• Crusted papules.
• Crusts.
• Epidermal collarettes.
• Circular erythematous or hyperpigmented 
patches (macules).
• Alopecia; moth-eaten hair coat.
• Hemorrhagic bullae.
• Scaling.
• Lichenification.
• Erosions.
• Ulcerations.
• Target lesions.
• Abscess.
• Furunculosis, cellulitis.
CAUSES
• Staphylococcus pseudintermedius —most 
frequent dogs and cats.
• Pasteurella multocida —cats.
• Deep bacterial skin infections may be 
complicated by Gram-negative organisms (e.g., 
Escherichia coli , Proteus  spp., Pseudomonas  spp.).
• Rarely caused by higher bacteria (e.g., 
Actinomyces , Nocardia , Mycobacteria , 
Actinobacillus ).
• Hypersensitivity—flea allergic dermatitis; 
atopic dermatitis; cutaneous adverse reaction 
to food; contact allergic dermatitis.
• Parasites—especially Demodex  spp.
• Fungal infection—dermatophytosis 
(Microsporum canis , Microsporum gypseum , or 
Trichophyton mentagrophytes ) most common.
• Endocrine diseases—hypothyroidism; 
hyperadrenocorticism; sex hormone imbalance.
• Immunosuppression—excessive cortico -
steroid administration; young animals.
• Seborrhea—chin acne; schnauzer comedo 
syndrome.
• Conformation—short coat; skin folds; 
redundant interdigital skin.
• T rauma—pressure points; grooming; 
scratching; rooting behavior; irritants.
• Foreign body—foxtail; grass awn.
  DIAGNOSIS
• Hypersensitivity—pruritus precedes lesions; 
persists with resolution of pyoderma.
• Flea allergic dermatitis or atopic dermatitis—  
may be seasonal.
• Endocrinopathy—relapsing pyoderma; 
consider if not associated with pruritus or 
pruritus resolves with resolution of the pyoderma; may be associated with systemic 
symptoms.
• Pustular diseases—dermatophytosis; 
demodicosis; pemphigus foliaceus; and 
subcorneal pustular dermatosis.
• Deep furunculosis—higher bacterial 
infection; demodicosis; dermatophytosis; 
opportunistic fungal infections; deep fungal 
infections; panniculitis; and zinc-responsive 
• Superficial pyoderma in short-coated breeds 
often misdiagnosed as urticaria due to acute 
onset of pruritic papules and follicular tufting.
• Superficial pyoderma—normal or may 
reflect underlying cause (e.g., anemia due 
to hypothyroidism; stress leukogram and 
high serum alkaline phosphatase due to 
hyperadrenocorticism; eosinophilia due to 
parasitism).
• Generalized, deep pyoderma—may 
demonstrate leukocytosis with a regenerative 
left shift and hyperglobulinemia; abnormalities 
related to an underlying cause may be present.
N/A
• Multiple skin scrapings—demodicosis.
• Direct smear from intact pustule—
neutrophils with intracellular bacteria, 
typically cocci.
• Cytology from underneath a crust or edge 
of an epidermal collarette; help differentiate 
pemphigus foliaceus (acantholytic 
keratinocytes) and deep fungal infections 
(blastomycosis, cryptococcosis) from 
pyoderma; tissue grains may identify 
filamentous organisms characteristic of 
higher bacteria.
• T richograms—dermatophytosis, follicular 
• Surface or papule/pustule cytology—
pemphigus foliaceus.
• Elimination diet trial—food hypersensitivity.
• Endocrine tests—hypothyroidism, 
• Skin biopsy is rarely useful unless the 
infection is deep in nature; utilized to obtain 
tissue sample for macerated tissue culture.
• Recommended in recurrent cases and/or 
failure to respond to empiric antibiotics.
• Often positive for S. pseudintermedius .
• Other organisms besides staphylococci and 
higher bacteria may be cultured from lesions 
of deep pyoderma.
• Contents of an intact pustule—most 
reliable results for superficial infections.
• Punch biopsy obtained utilizing sterile 
technique for macerated tissue culture; 
especially and removal of the epidermis for Pyoderma

Canine and Feline, Seventh Edition  1163
Pdeep pyoderma; more likely false-negative 
results with superficial pyoderma.
• Freshly expressed exudate from a draining 
tract or from beneath a crust—may yield the 
pathogen or a contaminant if the lesion is not 
intact.
• Subcorneal pustules.
• Intraepidermal neutrophilic microabscesses.
• Perifolliculitis.
• Folliculitis.
• Furunculosis.
• Nodular to diffuse dermatitis.
• Inflammatory reaction—suppurative or 
pyogranulomatous.
• Tissue grains within pyogranulomas—
observed most often with Actinomyces , 
Actinobacillus , and Nocardia .
• Special stains—used to identify Gram-
negative bacteria or acid-fast organisms.
  TREATMENT
Usually outpatient, except for severe, 
generalized deep pyoderma.
• Severe, generalized, deep pyoderma—may 
require IV fluids, parenteral antibiotics, and/
or daily whirlpool baths.
• Benzoyl peroxide or chlorhexidine 
shampoos—remove surface debris.
• Frequent topical therapy can help reduce 
the severity and frequency of recurrence.
• Whirlpool baths—deep pyoderma; remove 
crusted exudate; encourage drainage; decrease 
inflammation and improve tissue oxygenation.
DIET
Novel protein or hydrolysate diet if secondary 
to cutaneous adverse reaction to food.
Fold pyoderma may require surgical 
correction to prevent recurrence.
• S. pseudintermedius  isolates—usually 
susceptible to cephalosporins, amoxicillin–
clavulanate, erythromycin, clindamycin, and 
trimethoprim–sulfamethoxazole; somewhat 
less responsive to lincomycin; frequently 
resistant to amoxicillin, ampicillin, 
penicillin.• Amoxicillin–clavulanate—most isolates of 
Staphylococcus  and P . multocida  susceptible; 
generally effective for skin infections in cats.
• Superficial pyoderma—initially treated 
empirically with one of the antibiotics listed 
above.
• Recurrent, resistant, or deep infections—
choose antibiotic therapy based upon 
culture and susceptibility testing (e.g., 
chloramphenicol).
• Multiple organisms with different antibiotic 
susceptibilities—select antibiotic on basis of 
the staphylococcal susceptibility.
Corticosteroids—mask inflammation causing 
therapy to be discontinued prematurely and 
resulting in selection for resistant organisms; if 
used concurrently, therapy should be extended 
and the patient should be reevaluated before 
discontinuing antibiotic therapy.
• Cephalosporins, erythromycin, lincomycin, 
and clindamycin—vomiting; administer with 
food.
• Aminoglycosides—renal toxicity usually 
precludes prolonged systemic use.
• T rimethoprim–sulfamethoxazole—kerato -
conjunctivitis sicca, fever, hepatotoxicity, 
polyarthritis, and hematologic abnormalities, 
especially neutropenia; not recommended for 
use in Doberman pinschers.
• Chloramphenicol—use with caution in cats; 
mild, reversible anemia in dogs (uncommon); 
associated with aplastic anemia in humans; 
rear temporary limb muscle weakness is a 
possible side effect.
T rimethoprim-sulfamethoxazole—falsely 
decreased thyroid hormone test results.
Bacterin (Staphage Lysate, Delmont 
Laboratories), staphoid AB, or autogenous 
injections—may improve antibiotic efficacy 
and decrease infection recurrence.
  FOLLOW-UP
Administer oral antibiotics for a minimum 
of 7–10 days beyond clinical cure; approx -
imately 3–4 weeks for superficial pyoderma; 
6–10 weeks for deep pyoderma.
• Routine bathing with benzoyl peroxide or 
chlorhexidine shampoos—may help prevent 
recurrences.• Padded bedding—may ease pressure point 
pyoderma; also consider causes for poor 
wound healing including hypothyroidism.
• Topical benzoyl peroxide gel or mupirocin 
2% ointment may be helpful adjunct 
therapies—chin acne, fold pyoderma, 
• Identification and management of the 
underlying cause is crucial to prevent 
Bacteremia and septicemia.
Likely to be recurrent or nonresponsive if 
underlying cause is not identified and 
effectively managed.
N/A
• Impetigo—affects young dogs before 
puberty; can be associated with poor 
husbandry; often requires only topical therapy.
• Superficial pustular dermatitis—occurs in 
kittens; associated with overzealous “mouthing” 
by the queen.
• Pyoderma secondary to atopic dermatitis—
usually begins between 1 and 3 years of age.
• Pyoderma secondary to endocrine disorders—
usually begins in middle adulthood.
• Cutaneous tuberculosis—rare.
• Feline leprosy—unknown.
N/A
SEE ALSO
• Perianal Fistula.
• Pododermatitis.
Helton Rhodes KA, Werner A. 
Blackwell’s Five-Minute Veterinary 
Consult: Clinical Companion: Small 
Animal Dermatology, 3rd ed. Hoboken, NJ: 
Resnick
available online(continued)  Pyoderma

1164  Blackwell’s Five-Minute Veterinary Consult  
P  BASICS
OVERVIEW
• Staphylococcal bacterial skin infection 
resistant to all β-lactam antibiotics. 
• Most often caused by Staphylococcus 
pseudintermedius ; rarely Staphylococcus aureus .
• More common with chronic, primary skin 
conditions; associated with exposure to one or 
more courses of antibiotic therapy. 
• Pyoderma less common in cats.
SIGNS
• Papules. •  Pustules. •  Crusts. •  Crusted 
papules. •  Epidermal collarettes. 
• Furunculosis, cellulitis if deep. •  Circular 
erythematous or hyperpigmented spots 
(macules). •  Alopecia, moth-eaten hair coat, 
especially in short-coated breeds. 
• Hemorrhagic bullae. •  Scale. 
• Lichenification. •  Abscess. •  Pyoderma 
that persists despite appropriate empiric 
therapy.
to food; contact allergic dermatitis. 
• Parasites—especially Demodex  spp. 
• Endocrine—hypothyroidism; hyperadreno -
corticism (especially if nonpruritic). 
• Immunosuppression—iatrogenic due to 
chronic glucocorticoid therapy; young 
animals. •  Seborrhea—chin acne; schnauzer 
comedo syndrome. •  Additional—short coat; 
skin folds; redundant interdigital skin; trauma 
of pressure points, especially in hypothyroid 
dogs; excessive grooming; scratching; rooting 
behavior; irritants; foreign bodies (foxtail; 
grass awn).
  DIAGNOSIS
Dogs
• Demodicosis. •  Dermatophytosis. 
• Methicillin-sensitive pyoderma. 
• Pemphigus foliaceus. •  Systemic lupus 
erythematosus. •  Other primary causes for 
pyoderma. •  Epitheliotropic lymphoma 
(older animals).
Cats
• Dermatophytosis. •  Flea-allergic dermatitis. 
• Demodicosis. •  Pemphigus foliaceus. 
• Epitheliotropic lymphoma in older 
animals.CBC/BIOCHEMISTRY/URINALYSIS
Generalized, deep pyoderma—may 
demonstrate leukocytosis with regenerative 
left shift and hyperglobulinemia; in addition, 
may reflect underlying cause; sepsis is a 
concern, especially if patient is 
immunosuppressed.
• Culture and susceptibility testing— essential  
when methicillin-resistant infection is 
suspected; should be performed when there is 
inadequate response to empiric treatment 
with antibiotics or in cases with a history of 
methicillin-resistant S. pseudintermedius  
(MRSP). •  Multiple skin scrapings—
demodicosis. •  Direct smear from intact 
pustule—neutrophils with intracellular 
bacteria. •  Cytology—from underneath crust 
or edge of epidermal.collarette. •  Skin 
biopsy—rarely useful unless infection deep; 
used to obtain tissue sample for macerated 
tissue culture. •  Dermatophyte culture—
fungal infection. •  Intradermal allergy 
testing—atopic dermatitis. •  Elimination diet 
trial—cutaneous adverse reaction to food. 
• Endocrine tests—hypothyroidism, hyper  - 
adrenocorticism.
• Subcorneal pustules. •  Intraepidermal 
neutrophilic microabscesses. •  Perifolliculitis. 
• Folliculitis. •  Furunculosis—deep 
infection. •  Nodular to diffuse dermatitis. 
• Panniculitis—deep infection. 
• Inflammatory reaction—suppurative; 
pyogranulomatous with deep infections.
  TREATMENT
• Topical therapy essential—chlorhexidine 
shampoo or spray, dilute bleach bathing, 
mupirocin ointment, for localized disease. 
• Some cases resolve with topical therapy 
only—must be consistent/frequent. 
• Generalized, deep pyoderma—hospitali -
zation, IV fluids, IV antibiotics, whirlpool 
baths, depending on severity and risk for sepsis.
• Antibiotic therapy must be based on culture 
and susceptibility data. •  Appropriate anti  - 
biotics must be administered long enough to 
resolve infection.
Corticosteroid steroids—masks inflammation 
and suppresses immune system function; 
therapy should be discontinued. Oclacitinib—  may suppress immune system function and 
delay resolution.
  FOLLOW-UP
Regular reevaluation of patient while still 
receiving treatment aids in decision regarding 
continuation of therapy or need for additional 
diagnostic tests.
• Choose antibiotic therapy from culture and 
susceptibility data—treatment failure occurs 
when antibiotic changes made without 
evidence. •  Successful management of 
underlying disease. •  Handwashing before 
and after handling patient.
• Good if antibiotic choice is based on 
culture and susceptibility data and underlying 
cause is managed. •  Methicillin-resistant 
infections not more virulent, but fewer 
antibiotic choices available for treatment.
• Exposure of humans and animals to 
methicillin-resistant S. aureus  (MRSA) and 
MRSP is common. •  MRSP infections in 
humans are rare. •  MRSP is not MRSA—
MRSA infections in animals are rare and 
most associated with exposure to humans 
with MRSA infection.
SEE ALSO
• MRSA = methicillin-resistant S. aureus . 
• MRSP = methicillin-resistant S. 
Weese SJ: www.wormsandgermsblog.com
2018.
ResnickPyoderma—Methicillin-Resistant

Canine and Feline, Seventh Edition  1165
P  BASICS
Pyometra is a bacterial suppurative 
inflammation of the endometrium leading to 
intraluminal accumulation of purulent 
exudate within the uterus.
• Incompletely understood and 
• Classic theory—repeated exposure of 
endometrium to high concentrations of 
estrogen during proestrus and estrus 
followed by high concentrations of 
progesterone during diestrus without 
pregnancy leads to development of cystic 
endometrial hyperplasia (CEH), which 
predisposes uterus to ascending bacterial 
• Strains of Escherichia coli  with 
uropathogenic virulence factors that allow 
adhesion to the endometrium and establish­
ment of an infection without CEH enter 
uterus during proestrus and estrus and act as 
a mucosal irritant stimulating development of 
CEH under the influence of progesterone. 
Uterine secretions may act as a growth 
medium for ascending bacteria.
• Regardless of underlying cause, pyometra 
does not occur in absence of progesterone 
(endogeneous or exogeneous).
GENETICS
• Genetic predisposition suspected in some 
related bitches.
• Suggested breed predisposition in Bernese 
mountain dog, Rottweiler, rough ­coated 
collie, oriental cat breeds.
Accurate assessment difficult because most 
dogs and cats in the United States undergo 
elective ovariohysterectomy (OHE). A recent 
Swedish study reported overall incidence of 
pyometra in bitches as 199 per 10,000 dogs 
at risk and in queens as 17 per 10,000 cats at 
risk. Lower incidence in queens because they 
are induced ovulators.
Species
Usually >6 years old; range 4 months to 16 
years; mean 7.25 years.
• Female—ovary intact.
• Spayed bitches and queens with ovarian 
remnant syndrome may develop a stump 
pyometra.SIGNS
• Dogs—usually within 12 weeks of last estrus.
• Cats—usually within 4 weeks of last estrus.
• History of treatment with estrogens and/or 
• Uterus—may be enlarged on abdominal 
• Systemic illness—depends on duration and 
severity.
• Open cervix—bloody, purulent vaginal 
discharge, may not be noticed in queens.
• Closed cervix—systemically ill from 
endotoxemia and bacteremia: polyuria, 
polydipsia, lethargy, inappetence/anorexia, 
vomiting, abdominal distension, dehydration, 
shock.
• Pyrexia.
CAUSES
• Dogs—repeated exposure of endometrium 
to estrogen followed by prolonged exposure 
to progesterone without pregnancy.
• Cats—may be the result of estrogen at 
estrus followed by a progestational (pseudo­
pregnancy) phase caused by spontaneous 
ovulation or ovulation induction.
• Middle ­aged to older, nulliparous ovary ­
intact females may be predisposed.
• Pharmacologic use of estrogen (mismate 
shot) during midestrus to early diestrus.
• No correlation with pseudopregnancy in 
dogs.
• Long ­term and high ­dose use of 
progestagens (for estrus prevention) in both 
queens and bitches.
  DIAGNOSIS
• Vaginitis.
• Metritis and retained fetal membranes 
(associated within first days post partum).
• Hydrometra (serous intrauterine discharge); 
mucometra (mucoid intrauterine discharge); 
hematometra (hemorrhagic intrauterine 
discharge).
• Other causes of polyuria/polydipsia—
diabetes mellitus, hyperadrenocorticism, renal 
disease.
• Neutrophilia or neutropenia with left shift ± 
toxic change; more severe with closed cervix.
• Normocytic, normochromic anemia.
• Hyperglobulinemia, hyperproteinemia, 
hypoalbuminemia, hypercholesterolemia, 
elevated C ­reactive protein concentration.
• Azotemia.• Elevated alanine aminotransferase and 
alkaline phosphatase enzyme activities.
• Urinalysis—isosthenuria, bacteriuria, 
glucosuria, and proteinuria possible. Collect 
sample by catheterization of urinary bladder 
to avoid risk of uterine puncture with 
cystocentesis. Midstream urine sample may 
be contaminated by vaginal discharge.
• Cytologic examination of vulvar discharge—
degenerate neutrophils, phagocytized bacteria; 
may be indistinguishable from purulent 
discharge associated with vaginal disease 
(e.g., vaginitis, vaginal mass, foreign object). 
Vaginoscopy can confirm origin and rule out 
other causes of discharge.
• Bacterial culture and sensitivity—vulvar 
discharge sample to be taken directly from the 
uterus transcervically or cranial vagina with 
the aid of a vaginal speculum and guarded 
swab. A free ­catch urine sample can also be 
useful as the causative agent in the pyometra 
is often located in the bladder.
• Serologic testing for Brucella canis —rapid 
slide agglutination test as a screen; sensitive 
but not specific. If positive, recheck by an 
agar gel immunodiffusion test or bacterial 
culture of whole blood, lymph node aspirate, 
or vulvar discharge.
• Hormone assay—in most cases, progesterone 
concentration will be >2 ng/mL; important 
to measure in animals that present in anestrus, 
as treatment with a progesterone receptor 
antagonist will be ineffective.
IMAGING
• Enlarged, distended uterus (see Web Figure 1).
• Rule out pregnancy— fetal skeletal 
ossification occurs 45 days after ovulation.
• Uterine horns distended with intraluminal 
fluid, with or without flocculation. Uterine 
wall thickened with irregular edges and small 
hypoechoic areas consistent with cystic 
change (CEH) (see Web Figure 2), uterine 
wall can appear thin if severely distended; 
monitoring of the volume of uterine fluid is 
necessary during medical therapy; presence of 
severe CEH and/or ovarian cysts associated 
with poorer prognosis for medical manage­
ment and fertility.
• Rule out pregnancy—20–24 days after 
• Pyometra may rarely occur with pregnancy 
in dogs.
Vaginoscopy—indicated in dogs with 
purulent vulvar discharge and no apparent 
uterine enlargement; allows determination 
of site of origin of the discharge; not possible 
in cats.Pyometra

1166  Blackwell’s Five-Minute Veterinary Consult  
PPATHOLOGIC FINDINGS
• Endometrium (dogs and cats)—
cobblestone appearance (see Web Figure 3).
• Cystic endometrial surface—covered by 
malodorous, mucopurulent exudate; 
thickened by increased endometrial gland size 
and cystic gland distension.
  TREATMENT
• Inpatient; life ­threatening condition if the 
cervix is closed, resulting in endotoxemia, 
bacteremia, and sepsis. Resuscitation requires 
immediate IV fluid administration and 
broad ­spectrum antibiotics to stabilize for 
• Open ­cervix pyometra may be a candidate 
for medical therapy.
• Medical treatment only recommended for 
valuable, young (<4 years) breeding animals 
that are not azotemic and systemically well. 
For all other animals, OHE is the treatment 
of choice. The prognosis for successful 
medical treatment and future fertility in older 
animals and animals with evidence of uterine 
and ovarian pathology is poor.
• Historically, medical treatment of closed ­
cervix pyometra was associated with uterine 
rupture and peritonitis, but new pharmaco­
logic agents and treatment protocols now 
make this a rare event.
• Bitches that are refractory or chronic cases 
that do not respond to medical treatment are 
candidates for OHE.
• Warn of possible recurrence of pyometra 
after medical therapy—important to breed at 
the next heat and spay when desired number 
of litters is achieved.
• Complete OHE is the preferred treatment 
in all animals not intended for breeding, older 
bitches (>4 years), bitches with evidence of 
chronic CEH changes and/or ovarian 
follicular cysts, bitches that present 
systemically unwell and require immediate 
emergency care and stabilization.
• Patients should be systemically stabilized 
prior to anesthesia for surgery (correction of 
any acid–base derangements, dehydration, 
hypotension, shock, electrolyte abnormalities, 
arrythmias) and administered IV fluids and 
IV broad ­spectrum antibiotics.
• Closed ­cervix pyometra—exercise great care 
in handling the enlarged and friable uterus 
(see Web Figure 4).
• Place saline ­soaked laparotomy sponges in 
abdomen to prevent leakage of purulent 
material into peritoneal cavity.  MEDICATIONS
• Empirical, pending results of bacterial 
culture and sensitivity:
 ◦Broad ­spectrum—ampicillin 22 mg/kg 
PO, IV q8h; amoxicillin and clavulonic 
acid 22 mg/kg, PO, q12h; ampicillin and 
sulbactam 22–30 mg/kg IV q8–12h or 
cefazolin 22 mg/kg IV, IM q8h combined 
with enrofloxacin 5–10 mg/kg PO q24h.
 ◦Continue for at least 14 days after 
resolution of vulvar discharge and fluid in 
uterine lumen.
• Rationale of medical therapy—remove 
progesterone and its effects on uterus, eliminate 
bacteria from uterus, promote cervical dilation 
and drainage of pus from the uterus.
Aglepristone
• Progesterone receptor antagonist; 
competitively binds to progesterone receptor 
with greater affinity than natural progesterone, 
preventing biological effect of progesterone. 
Will not lower progesterone levels.
• Dose—10 mg/kg SC, days 1, 2, 8, and if 
not cured day 14 and 28 in bitches. An 
additional injection at day 5 has been 
associated with an improved treatment 
success rate. In queens, 15 mg/kg SC is 
recommended. Minimal side effects. Excellent 
choice for closed pyometras as it dilates the 
cervix with minimal uterine contractions. 
Evacuation of uterus may be improved by 
adding prostaglandin. Aglepristone is not 
registered or approved by FDA in United 
States and not suitable for use in bitches with 
poor liver or kidney function.
Prostaglandins (PGF2 α)
• Doses listed here for native compound only 
(dinoprost tromethamine; Lutalyse®); has 
both luteolytic and ecobolic actions.
• Lower doses minimize side effects and 
ecobolic effect, especially in closed pyometras. 
Once the cervix is fully dilated the dose can 
be gradually increased if tolerated.
• Animals should be monitored in hospital 
for at least 1 hour after each treatment. If 
animal is systemically well, may be managed 
as outpatient.
• Side effects (dose ­dependent)—tachypnea, 
vomiting, diarrhea, urination, anxiety; seen 
20 minutes after administration and last for 
15–30 minutes. Use of PGF2 α in brachy­
cephalic breeds is contraindicated due to their 
predisposition to bronchospasm.
• Dogs and cats—10  μg/kg SC q5 ­6h day 1, 
then increase to 20–25  μg/kg q5–6h if 
tolerated for 1–2 days; then increase to 50  μg/
kg q5–6h for 3–4 days. Queens are more 
resistant to PGF2 α than bitches; often higher 
doses for longer periods are required.Cloprostenol
• Synthetic PGF2 α analogue; longer action 
(>30 hours) than natural form of PGF2 α.
• Dogs—1  μg/kg SC q24h for 7–14 days; 
convenience of once a day or every 2–3 days 
treatment but greater side effects, stimulates 
less uterine contractions and prolonged time 
to resolution compared to natural form of 
PGF2 α.
Dopamine Agonists
Cabergoline (5  μg/kg PO q24h for 7–14 days) 
or bromocriptine (10–20  μg/kg PO q8h); both 
given with food to reduce risk of vomiting; 
cabergoline has fewer side effects. Prolactin 
antagonists (e.g., have luteolytic action); best 
used in combination with PGF2 α—should see 
cervical opening within 24–48 hours. Only 
effective after 25 days post ovulation.
High ­dose PGF2 α and cloprostenol cause 
strong uterine contractions that may cause 
uterine rupture or force purulent exudate 
through the oviducts if used with closed ­
cervix pyometra.
Misoprostol—synthetic PGE1 analogue 
(10 μg/kg PO or 200  μg tablet in <20 kg and 
400 μg in >20 kg bitch intravaginally). Side 
effects minimal, facilitates cervical relaxation. 
Best used in combination with aglepristone 
and PGF2 α (PGE1 does not induce luteolysis).
  FOLLOW-UP
• OHE—For patients not responding to 
medical treatment within 5 days or those 
refractory to medical treatment.
• Clinical improvement should be seen 
within 48 hours after initiation of treatment:
 ◦Vaginal discharge—should reduce in 
volume and character over 5 days.
 ◦Ultrasonography—to assess response to 
treatment; reduction in uterine wall 
thickness and intraluminal fluid should be 
seen within 3 days after start of treatment; 
fluid in lumen should be absent within 
5–7 days.
• Serum progesterone concentrations decline 
within 48 hours of treatment with PGF2 α 
and should be <2 ng/mL at 5–7 days; 
recurrence of pyometra can occur if complete 
luteolysis not achieved.
• CBC should return to normal within 2 weeks.
• Continue treatment until no vulvar 
discharge is present and no fluid is seen 
within uterus on ultrasound. Prolonged 
treatment correlated with poor fertility.
• Animals not intended for breeding should 
be spayed.Pyometra  (continued)

Canine and Feline, Seventh Edition  1167
P• Exogenous progestagens for estrus 
suppression should be used with caution.
• Breeding females should be bred while they 
are young (<4 years) and spayed as soon as the 
desired number of litters has been obtained; a 
pregnant uterus reduces the risk of developing 
pyometra and maximizes uterine health.
• Animals that have been medically treated 
for pyometra should be bred on the very next 
estrus; gravid uterus is less susceptible to 
reinfection.
• Antimicrobial therapy at subsequent heat 
may or may not be helpful (controversial). 
Antibiotic selection based on culture and 
sensitivity of uterine fluid until 21 days of 
• Mibolerone (androgen ­receptor agonist) 
may be helpful following medical treatment 
of pyometra to postpone subsequent heat and 
allow endometrium to repair.
• Recurrence of pyometra at subsequent heats.
• Uterine rupture leading to sepsis.
• Bacteremia ­associated infection affecting 
various organs (i.e., uveitis, septic arthritis, 
osteomyelitis, etc.).EXPECTED COURSE AND PROGNOSIS
• Prognosis for survival is good if uterine 
rupture does not occur; 4% mortality rate in 
bitches and 8% in queens.
• Prognosis for response to medical therapy is 
good, especially if young, healthy animals 
(average 86% in bitches; 95% in queens).
• Recurrence rate of pyometra is dependent 
on age, parity, and preexisting uterine 
pathology (reported range 20–65%).
• Variable pregnancy rates reported after 
treatment for pyometra (50–90%).
Pyometra of the uterine stump in spayed 
animals—may develop any time after 
ovariohysterectomy; associated with ovarian 
remnant.
Drugs used for treatment of pyometra are 
abortificants—always rule out pregnancy 
before administration, caution while handling.SEE ALSO
• CEH = cystic endometrial hyperplasia.
• OHE = elective ovariohysterectomy.
• PGF2 α = prostaglandin F2 α
Hagman R. Pyometra in small animals. Vet 
48(4):639–661.
Hagman R, Lagerstedt AS, Hedhammar Å, 
Egenvall A. A breed ­matched case ­control 
study of potential risk ­factors for canine 
pyometra. Theriogenology 2011, 
75(7):1251–1257.
Authors  Fiona Hollinshead and Natali 
Krekeler
available online(continued)  Pyometra

1168  Blackwell’s Five-Minute Veterinary Consult  
P  BASICS
Accumulation of septic suppurative 
inflammation in the pleural cavity.
• Infectious—from transpulmonary, 
transesophageal, or transthoracic inoculation 
of bacteria into the pleural space, with 
subsequent suppurative pleuritis. •  Dogs—
often associated with an inhaled grass awn or 
other foreign object or a penetrating wound 
to the thorax. •  Other causes include 
extension of discospondylitis, esophageal 
perforation, parasitic migration, hemato­
genous spread, previous thoracic surgery, and 
neoplasia with abscess formation. •  Cats—
most commonly associated with penetrating 
bite wounds, foreign bodies, or aspiration of 
oropharyngeal flora and extension of 
subsequent pneumonia into the pleural space.
• Respiratory. •  Cardiovascular. •  Renal—
protein ­losing nephropathy.
Etiology is regionally dependent. For 
example, inhaled grass awn or foxtails are 
common in the western United States. 
Spirocerca lupi  should be considered as a 
predisposing cause in endemic areas (Africa, 
Asia, southeastern United States).
Species
Dogs—hunting and sporting breeds; for 
example, Labrador retrievers, German 
shorthaired pointers, springer spaniels, and 
border collies.
Median ∼4 years, although there is wide 
variation.
Male animals overrepresented.
SIGNS
• Often insidious in onset, with few clinical 
signs until late in the course of disease. 
• Respiratory compromise—often not severe 
unless disease is advanced. •  Vomiting/
diarrhea may be initial presenting complaint 
in 25% of canine cases.
• Diminished activity. •  Collapse after 
exercising and slow recovery. •  Weight loss 
and partial anorexia can be the only clinical 
signs.Physical Examination Findings
• Tachypnea. •  Cachexia. •  Cough. 
• Pyrexia. •  Thoracic auscultation—muffled 
heart and lung sounds. •  Cats—may show 
few clinical signs before onset of apparently 
acute respiratory distress, collapse, and septic 
shock; bradycardia and hypersalivation 
associated with poor outcome. •  Injury to the 
thoracic wall—may not be apparent or may 
be healed at the time of examination.
CAUSES
• Infectious—Dogs: Actinomyces  spp., 
Nocardia  spp., anaerobes ( Bacteroides , 
Peptostreptococcus , Fusobacterium ), 
Corynebacterium , Escherichia coli , Pasteurella , 
and Streptococcus  spp.; fungal agents. Cats: 
oral commensals (e.g., Pasteurella multocida  
and Bacteroides  spp.) most common; obligate 
anaerobes ( Peptostreptococcus , Fusobacterium ) 
common. •  Parasitic—Dogs: esophageal 
rupture of S. lupi  granuloma. •  Neoplastic—
rarely with intrathoracic tumors secondary to 
tumor necrosis.
• Dogs—hunting, field trials, and other 
strenuous outdoor sporting activities; S. lupi  
endemic areas. •  Cats—multiple cat house­
holds, outdoor cats, pneumonia, upper 
respiratory infection.
  DIAGNOSIS
• Other pleural effusions—chylothorax and 
hemothorax; nonseptic exudates (feline 
infectious peritonitis or neoplasia); 
transudative effusions; differentiated via 
cytologic examination. •  Diseases associated 
with fever of unknown origin should be 
considered for animals with nonlocalizing 
signs.
• Marked neutrophilic leukocytosis with left 
shift, monocytosis, and anemia of chronic 
disease. •  Regenerative anemia—can be seen 
with substantial hemorrhage into the pleural 
cavity. •  Hyperglobulinemia—possible due 
to chronic inflammation. 
• Hypoalbuminemia as a negative acute ­
phase reactant or due to renal loss, if 
glomerulonephritis results from chronic 
antigenic stimulation. •  Azotemia—prerenal 
and/or renal.
IMAGING
• Radiography—unilateral or bilateral pleural 
effusion with pleural fissure lines; pulmonary 
parenchymal lesions (consolidation, atelectasis, 
masses) common; mediastinal lesions 
possible. •  Ultrasonography—pleural 
effusion; may show marked amount of 
fibrinous deposition in the pleural space; may identify consolidated lung masses, mediastinal 
masses, and abscessed or neoplastic lung 
nodules. •  CT—focal interstitial to alveolar 
pulmonary opacities; pleural thickening; 
enlarged intrathoracic lymph nodes; pleural 
effusion; pneumothorax; and foreign body 
Thoracocentesis
• Cytologic evaluation—necessary to confirm 
the diagnosis; many effusions appear grossly 
hemorrhagic. •  Gram stains—can facilitate 
early identification of pathogenic organisms. 
• Sulfa granules (small accumulations of 
purulent debris) in the exudate—characteristic 
of infection by filamentous organisms (e.g., 
Actinomyces  and Nocardia ). • Organisms are 
often seen on cytologic examination, often 
within degenerative neutrophils.
• Culture fluid samples aerobically and 
anaerobically. Consider Mycoplasma  culture if 
standard cultures are negative. •  Filamentous, 
anaerobic organisms are slow ­growing or 
difficult to grow; cultures should be 
maintained longer than standard samples. 
• Sulfa granules—maceration may enhance 
culturing; contain higher concentrations of 
bacteria. •  Fungal organisms—culture 
depends on history and geographic location. 
• Urine samples—culture with suspected 
If S. lupi  is suspected.
• Fibrinous and suppurative pleuritis, with or 
without pulmonary abscessation. •  Organisms 
may be identified on histopathology. 
  TREATMENT
• Inpatient—often for several days to weeks. 
• T reat like any abscess; drainage is critical—
without it resolution is highly unlikely. 
• Surgical exploration, debridement, and 
potential lobectomy required in some cases.
• Continuous evacuation via tube 
thoracostomy with low ­pressure suction 
through a perforated tube; use a large ­bore 
tube to minimize occlusion; continue until 
net drainage is <2–3 mL/kg/day and 
intracellular bacteria are no longer visible on 
Gram stain; drainage may be slightly higher 
with red rubber tubes because they are more 
irritating. •  Cats—usually require general 
anesthesia for tube placement. •  Dogs with 
severe respiratory compromise—may Pyothorax

Canine and Feline, Seventh Edition  1169
Psubstitute local anesthesia and regional 
analgesia for general anesthesia. •  Periodic 
thoracic radiography—to ensure proper tube 
placement, and lack of pocketing or loculation 
of exudate, determine whether bilateral tube 
placement is necessary; document primary 
pulmonary pathology that may not have been 
apparent on initial examination. •  Thoracic 
lavage—every 6–8 hours with warm, sterile 
saline; may help break down consolidated 
debris. Consider addition of heparin 
(1,500 units/L) to lavage fluid. •  Coupage 
(rapid thoracic percussion)—may help remove 
consolidated debris. •  Repeat bacterial culture 
if the patient fails to improve.
ACTIVITY
• Inpatient—encourage light exercise (10 
minutes every 6–8 hours); promotes 
ventilatory efforts and helps break down 
pleural adhesions. •  After discharge, 
gradually increase exercise over 2–4 months.
DIET
• High ­calorie food. •  Consider feeding tube 
placement if prolonged anorexia.
Warn client that the duration of treatment 
(inpatient and outpatient) is long and 
expensive; recurrence is possible with either 
• Surgery—higher cure rate expected with 
surgery if pulmonary abscessation, pleural 
fibrosis, lung lobe torsion, extensive loculation 
of pus is present, or if mediastinum is involved. 
• Thoracoscopy can be utilized as an 
intermediate step to assess degree of severity 
and need for more aggressive intervention. 
• Identified foreign body via thoracic 
imaging (radiography, ultrasound, or CT)—
thoracotomy and retrieval indicated; grass awns 
are uncommonly found, even during surgery.
• Ultimately, choice determined by results of 
in vitro  sensitivity testing. •  Suspected 
specific pathogen—initiate treatment before 
culture results are available; choose on the 
basis of common antibiotic sensitivities of 
particular organisms; Actinomyces  spp. and 
Bacteroides  (non ­fragilis ) spp. often susceptible 
to beta ­lactams or lincosamides; Nocardia  
spp. often susceptible to potentiated 
sulfonamides; obligate anaerobic bacteria 
(including B. fragilis ) susceptible to amoxicillin–clavulanic acid, chloramphenicol, 
and usually metronidazole; Pasteurella  spp. 
often susceptible to potentiated penicillins. 
• Ampicillin or amoxicillin with a 
β­lactamase inhibitor—ampicillin and 
sulbactam 20–30 mg/kg IV q8h followed by 
amoxicillin–clavulanic acid 12–25 mg/kg PO 
q8h when medications can be given orally. 
• Clindamycin 5.5–11.0 mg/kg IV or PO 
q12h. •  Multiple antibiotics occasionally 
• Required following thoracotomy or during 
thoracocentesis. •  Consider multimodal 
analgesia—systemic opioids, nonsteroidal 
anti­inflammatory drugs; intrapleural 
Glucocorticoids and immunosuppressive 
agents—avoid with infectious pyothorax.
Potentiated sulfas—can be associated with 
keratoconjunctivitis sicca, polyarthropathy, 
hypothyroidism, thrombocytopenia, and 
anemia, especially with prolonged use.
  FOLLOW-UP
• Decreasing thoracic fluid production, 
decrease in cell count in pleural fluid, and 
absence of bacteria usually noted within 4–7 
days indicate that drains can be removed. 
Fluid should be submitted for aerobic and 
anaerobic culture at the time of drain 
removal. •  Evaluate thoracic radiographs—
ensure adequate evacuation of fluid. 
• Antibiotics—continue for 1 month after 
the patient is clinically normal, the hemogram 
is normal, and there is no radiographic 
evidence of fluid reaccumulation; average 
duration of therapy is 3–4 months but may 
continue for 6–12 months or longer. •  Assess 
CBC and radiographs monthly—residual 
radiographic changes may be permanent, but 
fluid should be absent.
• Incorrect insertion of the thoracostomy 
tube—may prevent adequate drainage or 
produce pneumothorax; placement too far 
cranially may put pressure on brachial arteries 
and veins, resulting in unilateral limb edema 
or lameness; lung laceration during placement. 
• Persistent, recurrent pyothorax—
compartmentalization of exudate; premature 
discontinuation of treatment; pulmonary 
lesions. •  Chronic fibrosing pleuritis and poor performance after apparent recovery—may 
occasionally respond to further surgery. 
• Persistent granulomatous mediastinitis.
• With aggressive management—prognosis 
fair to excellent (60–90% survival). 
• Dependent on severity of clinical signs. 
• Overall better prognosis in dogs (83%) 
than in cats (62%). •  Return to performance—  
dependent on chronicity of disease and level 
of management.
• Retroperitoneal abscessation and 
discospondylitis caused by migration of a 
foreign body through the diaphragm into the 
retroperitoneal space—occasionally seen. 
• Glomerulonephropathy—can be reversible 
with successful resolution of pyothorax.
SYNONYMS
• Empyema. •  Pleurisy. •  Suppurative 
pleuritis.
SEE ALSO
• Dyspnea and Respiratory Distress. 
Bach JF , Balakrishnan A. Retrospective 
comparison of costs between medical and 
surgical treatment of canine pyothorax. Can 
Vet J 2015, 56:1140–1143.
Anim Pract 2014, 44:161–180.
Scott J, Singh A, Monnet E, et al. Video ­
assisted thoracic surgery for the 
management of pyothorax in dogs: 14 cases. 
Vet Surg 2017, 46:722–730.
Stillion JR, Letendre JA. A clinical review of 
the pathophysiology, diagnosis, and 
treatment of pyothorax in dogs and cats. 
J Vet Emerg Crit Care 2015, 25:113–129.
available online(continued)  Pyothorax

1170  Blackwell’s Five-Minute Veterinary Consult  
PPyrethrin and Pyrethroid Toxicosis
  BASICS
OVERVIEW
• Insecticides. • Pyrethrins—natural. 
• Pyrethroids—synthetic. • Based on cases 
managed by the ASPCA Animal Poison Control 
Center exposures reported by generic from most 
to least are permethrin, deltamethrin, flumethrin, 
etofenprox, pyrethrins, cyfluthrin, cyphenothrin, 
imiprothrin and lambda cyhalothrin. • Affect 
the nervous system—reversibly prolong sodium 
conductance in nerve axons, resulting in 
repetitive nerve discharges. • With the advent of 
oral insecticides, safer topicals, and improved 
client education pyrethrin/pyrethroid adverse 
event reports continue to decrease. In 2017, 
15.1% of all insecticide-related calls to the 
ASPCA Animal Poison Control Center were 
attributed to pyrethrin/pyrethroid-containing 
products.
More frequently in cats; small dogs; and 
young, old, sick, anemic, or debilitated 
animals.
SIGNS
• Result from immune-mediated allergic 
hypersensitivity and anaphylactic reactions, 
genetic-based idiosyncratic reactions, and 
neurotoxic reactions. • Mild—hypersalivation; 
paw flicking; ear twitching; mild depression; 
vomiting; diarrhea. • Moderate—protracted 
vomiting and diarrhea; marked depression; 
ataxia; muscle tremors. • Extreme dermal or 
oral overdose—may produce seizures or death. 
• Cats—sensitive to pyrethroids. Cats 
inappropriately treated with permethrin-
containing products for use on dogs, often 
develop muscle tremors, ataxia, seizures, 
hyperthermia, and death within hours if not 
treated. • Dogs may develop tremors following 
exposure to liquid or granular lawn products 
containing bifenthrin. • Allergic reactions—
urticaria; hyperemia; pruritus; anaphylaxis; 
shock; respiratory distress; (rarely) death.
• Cats—more sensitive; less-efficient metabolic 
pathways, combined with grooming habits. 
Direct contact with permethrin spot-on treated 
dogs. • Patients with subnormal body 
temperatures after bathing, anesthesia, or 
sedation—predisposed to clinical signs.
  DIAGNOSIS
• Exposure history (amount and frequency of 
product usage), type and severity of clinical signs, and onset and duration of clinical 
signs—must be consistent before a tentative 
diagnosis can be made. • Misapplication of 
permethrin-containing dog-only flea product 
on cats. • Organophosphorous compounds, 
carbamate, or d-limonene toxicosis. 
• Strychnine, metaldehyde, tremorgenic 
mycotoxins, methylxanthines, amphetamines, 
serotonergic drug overdose, alcohol intoxication 
from isopropyl alcohol-based sprays.
• Pyrethrins—analytical tests not generally 
available. • Pyrethroids—some compounds 
can be detected in tissues, especially on hair, 
to confirm exposure. Hair analysis for 
permethrin can be valuable when severity of 
the adverse event in cats is much greater 
than anticipated based on the reported 
product application. Cats with generalized 
full-body tremors or seizures after reported 
application of a cat-approved flea product 
are suspect for exposure to a permethrin-
containing product.
  TREATMENT
• Mild adverse reactions (salivation, paw 
flicking, and ear twitching)—often self-
limiting and resolve with no care. 
• Continued mild signs—bathe at home with 
a mild hand dish-washing detergent (strictly 
avoid hypothermia). • Patient saturated with 
spray products—dry with a warmed towel; 
brush. • Progression to tremors and ataxia—
hospitalize. • Bathing upon stabilization 
(tremors controlled) with liquid hand dish- 
washing detergent and warm water is critical. 
• Seriously affected patient—IV fluid support 
recommended. • Maintenance of a normal 
body temperature—critical.
• T remors or seizures—especially for cats 
exposed to permethrin; methocarbamol 
injectable at 55–220 mg/kg IV not to exceed 
330 mg/kg/day; administer one-half dose 
slowly IV, wait until the patient begins to 
relax, continue administration to effect; do 
not exceed 2 mL/min injection rate, and 
start with lower dose initially. • Diazepam at 
low dosages has been used to control minor 
hyperesthesia. Seizure control has been 
achieved with pentobarbital, propofol 
(3–6 mg/kg IV or 0.1 mg/kg/min CRI) and 
inhalant anesthetics. Methocarbamol 
remains the agent of choice and can also be used orally for treating mild tremors 
(50–100 mg/kg q8h; 30 minutes onset 
time). • Activated charcoal (2 g/kg PO) is 
rarely beneficial or recommended. 
• Emetics—rarely warranted.
Atropine sulfate—not antidotal; avoid; may 
cause tachycardia, CNS stimulation, 
disorientation, drowsiness, respiratory 
depression, and even seizures.
  FOLLOW-UP
• Proper application of flea-control 
products—greatly reduces reactions. 
• Reduction of salivation—spray onto a 
grooming brush; evenly brush through hair 
coat. • Liquids—term “dip” common; never 
submerge animal; pour on body; sponge to 
cover dry areas. • Premise products—do not 
apply topically unless labeled for such use; 
after treating house or yard, do not allow 
animal in the area until product has dried, 
and environment has been ventilated. • Do 
not apply dog-only products on cats. • Do 
not use permethrin spot-on products on dogs 
in households where cats groom or sleep in 
physical contact with dogs.
• Hypersalivation—may recur for several 
days after use of flea-control product when 
patient (especially cat) grooms itself. • Most 
clinical signs (mild to severe) resolve within 
24–72 hours.
Hansen SR, Villar D, Buck WB, et al. 
Pyrethrins and pyrethroids in dogs and cats. 
Compend Contin Educ Pract Vet 1994, 
16:707–713.
Kuo K, Odunayo A. Adjunctive therapy with 
intravenous lipid emulsion and 
methocarbamol for permethrin toxicity in 
2 cats. J Vet Emerg Crit Care (San Antonio) 
2013, 23(4):436–441.
Poppenga RH, Gwaltney-Brant SM, eds., 
161–169.

Canine and Feline, Seventh Edition  1171
P
Pyruvate Kinase Deficiency
  BASICS
OVERVIEW
• Red blood cells (RBCs) require energy in 
the form of ATP for maintenance of shape, 
deformability, active membrane transport, 
and limited synthetic activities; mature RBCs 
lack mitochondria and depend on anaerobic 
glycolysis for ATP generation.
• Pyruvate kinase (PK) catalyzes an important 
rate-controlling ATP-generating step in 
glycolysis; consequently, energy metabolism is 
markedly impaired in PK-deficient RBCs, 
resulting in shortened RBC lifespan and anemia; 
bone marrow compensation is reflected by 
erythroid hyperplasia and marked reticulocytosis.
• Hepatic failure may result from chronic 
iron overload.
• Autosomal recessive trait recognized in 
basenji, beagle, West Highland white terrier, 
Cairn terrier, miniature poodle, dachshund, 
Chihuahua, pug, American Eskimo, and 
Labrador retriever dogs, and in Abyssinian, 
Somali, and domestic shorthair cats.
• Heterozygous-deficient Bengal, Egyptian 
Mau, La Perm, Maine coon, Norwegian 
Forest, Savannah, Siberian, and Singapura cats.
• Affected homozygous animals are generally 
not recognized as abnormal until several 
months of age or adulthood.
SIGNS
• Affected cats are often asymptomatic.
• Signs of anemia and shock (lethargy, 
tachycardia, exercise intolerance, pale mucous 
membranes).
• Splenomegaly may be present.
• Systolic heart murmur due to anemia.
• Icterus is occasionally seen in cats but rarely 
in dogs, unless hepatic failure present.
• Affected dogs may be slightly smaller than 
normal for their breed and age and may 
exhibit weakness and muscle wasting.
• Affected cats may exhibit diarrhea, 
inappetence, poor coat quality, and weight loss.
• RBCs from normal adult dogs exhibit only 
one PK isozyme (the R-type).
• Breed-specific defects in the PKLR  gene 
result in erythrocyte PK deficiency in dogs.
• A common molecular defect in the PKLR  
gene has been described in cats.
  DIAGNOSIS
hemotropic mycoplasmosis, babesiosis, Heinz body hemolytic anemia, microangiopathic 
hemolytic anemia, and phosphofructokinase 
deficiency (dogs).
• Affected animals—negative Coombs’ test, 
no parasites or Heinz bodies in stained blood 
• Dogs—persistent macrocytic hypochromic 
anemia, with hematocrit (HCT) of 16–28% 
and reticulocyte counts of 15–50%.
• Cats—anemia is intermittent (HCT 
13–40%), with slightly to markedly increased 
aggregate reticulocyte counts.
• Normal or slightly high total leukocyte counts.
• Normal to slightly high platelet counts.
• Moderate to marked polychromasia, 
anisocytosis, and increased nucleated RBCs 
on stained blood films.
• Poikilocytosis in splenectomized dogs.
• Possible abnormal clinical chemistry findings, 
such as hyperferremia, hyperbilirubinemia, and 
slightly high serum alanine aminotransferase 
and alkaline phosphatase activities. 
Hyperglobulinemia common in cats.
• Normal urinalysis, except for bilirubinuria 
in dogs.
• Total RBC PK activity—low value 
diagnostic in cats and some dogs; many 
affected dogs have normal or high activities 
because of the expression of an M2 isozyme 
that does not normally occur in mature 
RBCs; approximately 50% of normal activity 
in heterozygous animals.
• Additional assays (e.g., enzyme heat 
stability test, measurement of RBC glycolytic 
intermediates, electrophoresis of isozymes, 
and enzyme immunoprecipitation)—to reach 
a diagnosis in dogs whose total enzyme 
activity is not low.
• DNA diagnostic tests—screening for cats 
and several dog breeds (available at http://
research.vet.upenn.edu/penngen).
  TREATMENT
• Affected animals can be cured by bone 
marrow transplantation or gene therapy.
• Splenectomy may reduce the severity of the 
anemia in cats.
Long-term treatment with iron-chelating 
drugs might prolong the life expectancy of 
affected dogs.  FOLLOW-UP
• Hepatic iron overload—develops in 
affected dogs; can result in cirrhosis and 
• Myelofibrosis and osteosclerosis—develop 
in affected dogs with age; most die by 5 years 
old as a result of bone marrow or liver failure.
• Severe anemia with minimal reticulocytosis 
or abnormal liver function tests and ascites 
secondary to hypoalbuminemia indicate the 
terminal stage of the disease in dogs.
• HCT = hematocrit.
• PK = pyruvate kinase.

1172  Blackwell’s Five-Minute Veterinary Consult  
P  BASICS
Infectious disease primarily affecting skin or 
gastrointestinal (GI) tract of dogs and cats; 
caused by the aquatic pathogen Pythium 
insidiosum , an organism in the class 
Oomycetes.
• Infective form of P . insidiosum  is thought to 
be a motile biflagellate zoospore, which is 
released into warm water environments and is 
chemotactically attracted to damaged tissue 
and animal hair; animals likely infected when 
they enter or ingest water containing infective 
zoospores.
• P . insidiosum  considered pathogenic 
rather than opportunistic because immune 
suppression is not prerequisite for infection.
• In GI tract, P . insidiosum  causes chronic 
pyogranulomatous disease with severe 
segmental transmural thickening of one or 
more areas of stomach or intestine.
• In skin, pythiosis typically causes non­
healing wounds and invasive masses that 
contain ulcerated nodules and draining tracts.
• GI and cutaneous forms of disease 
encountered with equal frequency in dogs; 
cats are infrequently infected, cutaneous form 
• With exception of occasional dissemination 
to regional lymph nodes, pythiosis usually 
affects only one body system in each patient; 
multisystemic involvement rare.
• GI pythiosis most often affects gastric 
outflow tract, proximal small intestine, 
ileocolic junction, colon, and mesentery; 
esophagus rarely affected.
• In dogs, GI disease, local thromboembolic 
events, or vascular invasion may lead to bowel 
wall ischemia, GI perforation, or hemoabdomen.
• Dogs with cutaneous pythiosis are often 
presented for solitary or multiple cutaneous 
or subcutaneous lesions involving extremities, 
tailhead, ventral neck, perineum.
• In cats, cutaneous lesions or subcutaneous 
masses involving retrobulbar, periorbital, or 
nasopharyngeal regions, tailhead, or footpads 
have been observed.
GENETICS
Large ­breed dogs most often affected; no 
genetic predisposition documented.
• Dependent on geographic distribution.
• Affected animals more often presented in 
fall or early winter.GEOGRAPHIC DISTRIBUTION
• Primarily in tropical and subtropical areas 
of the world.
• In United States, occurs most often in states 
bordering Gulf of Mexico, but documented 
in many other states.
• Outside the United States, reported in 
Australia, Brazil, Burma, Colombia, Costa 
Rica, Indonesia, Japan, New Guinea, and 
Thailand.
Species
Dog, less commonly cat.
• Large ­breed dogs, especially those in 
hunting or field trial work near water.
• Labrador retrievers overrepresented.
• German shepherd dogs may be predisposed 
to cutaneous pythiosis.
Animals <6 years old are most common.
Males affected more often than females, 
possibly due to increased exposure.
SIGNS
Dogs not usually severely ill until late in 
course of disease.
• Chronic weight loss, intermittent 
vomiting.
• Diarrhea if colon or large segment of small 
intestine affected.
• Regurgitation with esophageal disease.
• Cutaneous disease characterized by 
nonhealing wounds with nodules that drain 
and ulcerate.
GI Pythiosis
• Emaciation.
• Palpable abdominal mass.
• Despite severe weight loss, affected dogs 
usually bright and alert.
• Systemic signs and abdominal pain may 
occur with intestinal obstruction, infarction, 
or perforation.
Cutaneous Pythiosis
• Cutaneous or subcutaneous lesions appear 
as nonhealing wounds, edematous regions, or 
poorly defined nodules that ulcerate.
• Multiple tracts draining serosanguineous or 
purulent exudate.
CAUSES
P . insidiosum .
• Environmental exposure to swampy areas, 
bayous, ponds, or lakes containing infective 
• Outdoor activities such as hunting.  DIAGNOSIS
• Intestinal obstruction (foreign body, 
intussusception).
• Gastric or intestinal neoplasia (lympho­
sarcoma, carcinoma, etc.).
• Basidiobolomycosis, protothecosis.
• Histiocytic or idiopathic colitis.
• Lagenidiosis, paralagenidiosis (caused 
by oomycotic pathogens in genera 
Lagenidium  and Paralagenidium , 
respectively).
• Zygomycosis (infections caused by 
Basidiobolus  or Conidiobolus  spp.).
• Other mycotic skin diseases, such as 
cryptococcosis, coccidioidomycosis, 
sporotrichosis, eumycotic mycetoma, and 
phaeohyphomycosis.
• Nodular bacterial skin diseases, such as 
actinomycosis, mycobacteriosis, botryo­
mycosis, and brucellosis.
• Protothecosis or nodular leishmaniosis.
• Noninfectious pyogranulomatous diseases, 
such as foreign body reaction, idiopathic 
nodular panniculitis, sebaceous nodular 
adenitis, canine cutaneous sterile pyogranuloma/
granuloma syndrome.
• Systemic vasculitis and cutaneous embolic 
disease.
• Laboratory findings nonspecific.
• Eosinophilia, leukocytosis, anemia of 
chronic inflammatory disease possible.
• Hyperglobulinemia and/or hypoalbuminemia 
in chronically affected dogs.
• Hypokalemia, hyponatremia, hypo­
chloridemia, metabolic alkalosis, in dogs 
with gastric outflow obstruction.
• Hypercalcemia—reported in a single dog.
Serology—ELISA available at Auburn 
University College of Veterinary Medicine.
IMAGING
• Abdominal radiography may reveal 
obstructive pattern, bowel wall thickening, or 
• Abdominal ultrasonography may reveal 
segmental transmural thickening and 
loss of normal wall layering of the stomach, 
proximal small intestine, or ileocolic junction. 
Granulomas or enlarged lymph nodes may be 
evident in the mesentery.Pythiosis

Canine and Feline, Seventh Edition  1173
• Biopsy of GI or skin lesions demonstrates 
histologic changes suggestive of, but not 
definitive for, pythiosis.
• Definitive diagnosis is based on specific PCR 
amplification or sequencing of DNA extracted 
from infected tissue or cultured isolates; submit  
samples to experienced laboratory via 
overnight shipping at room temperature.
• GI and skin lesions characterized by 
pyogranulomatous and eosinophilic 
inflammation associated with broad (4–6  μm), 
irregularly branching, infrequently septate 
hyphae with thick, nonparallel walls.
• Predominance of eosinophils within 
inflammatory reaction differentiates pythiosis, 
lagenidiosis, zygomycosis from other mycotic 
• Hyphal organisms usually not visible on 
hematoxylin and eosin ­stained sections; 
readily visualized with silver stain.
• GI lesions—severe segmental thickening of 
portions of stomach and/or bowel, often with 
obstruction of intestinal lumen.
• Mesenteric lymphadenopathy is common, 
but presence of P . insidiosum  hyphae within 
lymph nodes is uncommon.
• GI pythiosis characterized by eosinophilic 
and pyogranulomatous inflammation with 
necrotic foci and discrete granulomas that 
contain hyphae.
  TREATMENT
T reatment of choice is aggressive surgical 
excision of all infected tissue with 3–5 cm 
margins. Unfortunately, many animals are not 
presented until late in disease when complete 
resection is not possible. Addition of prednisone 
at anti ­inflammatory dosages to antifungal 
therapy has improved efficacy of medical 
treatment for nonresectable GI pythiosis.
Supportive care should include IV fluids with 
potassium supplementation and nutritional 
support. Antibiotics may be indicated to treat 
secondary pyoderma in dogs with cutaneous 
lesions.
ACTIVITY
Limit activity.
DIET
Feed a highly digestible, calorie ­dense diet.
• T reatment is expensive.
• Prognosis for cutaneous pythiosis is guarded 
to poor unless complete resection with wide margins is feasible. For dogs with GI 
pythiosis, complete resolution of disease may 
occur when medical therapy includes 
• Attempt wide surgical excision to obtain 
5 cm margins (and two fascial planes deep if 
cutaneous).
• Amputation recommended for treatment of 
extremity lesions.
• Enlarged mesenteric lymph nodes should 
be biopsied but often do not contain 
infective hyphae, thus do not have to be 
removed.
• Dogs often improve after obstructive lesions 
are resected, even if significant gross disease is 
still present.
• Reevaluation of ELISA serology 2–3 
months after surgery may provide prognostic 
• Itraconazole 10 mg/kg PO q24h combined 
with terbinafine 10 mg/kg PO q24h and 
prednisone appears to be most effective 
 ◦Prednisone is given at 1 mg/kg PO q12h 
for 5–7 days, then q24h for 1 month, then 
slowly tapered if there is clinical improve ­ 
ment.
 ◦Antifungal therapy should be continued 
for minimum of 6 months.
 ◦Compounded bulk itraconazole should 
not be used; give with food.
• Azole drugs should not be used in animals 
with severe liver disease.
• Anorexia, high liver enzymes, and 
cutaneous vasculitis are most common 
adverse effects of itraconazole.
Antacids and anticonvulsants may decrease 
blood levels of itraconazole.
Prednisone used alone improves clinical 
signs in short term. In addition, the author 
has observed complete long ­term resolution 
of clinical signs in a small number of dogs 
with GI pythiosis treated with prednisone 
alone. This is not recommended as a 
primary treatment for dogs with resectable 
lesions, but should be considered as palliative 
therapy in dogs with nonresectable disease 
when client finances preclude use of anti ­ 
fungals.  FOLLOW-UP
• ELISA serology can be used to monitor 
response to therapy; serology should be 
checked 2–3 months after surgery or every 
3 months during medical therapy.
• Abdominal ultrasonography is useful for 
reevaluating intestinal lesions.
• Liver enzyme activities should be 
evaluated monthly while patient is on 
itraconazole.
Monitor for signs of recurrence.
Acute abdomen and death from GI 
thrombosis or perforation.
Prognosis is guarded unless a complete 
resection is possible.
Young animals are predisposed.
There is no evidence of direct transmission 
from animals to humans; infections in humans 
are very rare and are from a common environ­
mental source.
Azole antifungals are teratogenic and should 
not be used in pregnant animals.
SYNONYMS
• Phycomycosis.
• Swamp cancer.
Grooters AM. Pythiosis, lagenidiosis, and 
zygomycosis. In: Sykes JE, ed., Canine and 
Elsevier Saunders, 2014.
Med 2019, 33:1434–1439.
Author  Amy M. Grooters
available online(continued)  Pythiosis

1174  Blackwell’s Five-Minute Veterinary Consult  
P  BASICS
• White blood cells (WBCs) (i.e., neutrophils, 
eosinophils, monocytes, lymphocytes, or 
plasma cells) in urine.
• More than 5 WBCs per high-power field is 
generally considered abnormal, but the number 
of WBCs found in urinary sediment varies 
with method of collection, sample volume and 
concentration, degree of cellular destruction 
after collection, and laboratory technique.
• Large numbers of WBCs in voided urine 
indicate active inflammation along the 
• Can be associated with any pathologic process 
(infectious or noninfectious) that causes cellular 
injury or death; tissue damage evokes exudative 
inflammation characterized by leukocytic 
extravasation (pyuria) and increased vascular 
permeability (hematuria and proteinuria).
• Renal/urologic—urethra, urinary bladder, 
ureters, and kidneys.
• Genital—prepuce, prostate, vagina, and 
uterus.
SIGNS
• Historical and physical examination 
findings depend on the underlying cause, 
organ(s) affected, degree of organ 
dysfunction, and magnitude of systemic 
inflammatory responses.
• Nonobstructive lesions confined to the 
urinary bladder, urethra, vagina, or prepuce 
rarely cause systemic signs of inflammation. 
Systemic signs may accompany disease of the 
kidneys, prostate, or uterus.
Local Effects of Inflammation
• Erythema of mucosal surfaces.
• Tissue swelling.
• Exudation of leukocytes and protein-rich 
fluid.
• Pain.
• Loss of function.
Systemic Effects of Inflammation
• Fever.
CAUSES
Kidney
• Nephrolith.
• Neoplasia.• T rauma.
Ureter
• Ureteritis.
• Ureterolith.
• Ureteral stent.
• Cystitis.
• Urocystolith.
• T rauma.
• Overdistension—urethral obstruction.
• Pharmacologic—cyclophosphamide.
Urethra
• Urethritis.
• Urethrolith.
• T rauma.
Prostate
• Prostatitis/abscess.
Penis/Prepuce
• Balanoposthitis.
Uterus
• Pyometra/metritis.
Vagina
• T rauma.
• Any disease process, diagnostic procedure, 
or therapy that alters normal urinary tract 
defenses and predisposes to infection.
• Any disease process, dietary factor, or 
therapy that predisposes to formation of 
metabolic uroliths.
  DIAGNOSIS
Voided Specimens
• Rule out vaginitis—vaginal discharge, 
erythema of vaginal mucosa, licking of vulva, 
and attracting male dogs.
• Rule out pyometra, metritis—vaginal 
discharge, large uterus, pyrexia, depression, 
anorexia, polyuria, polydipsia, and a recent 
history of estrus, parturition, or progestin 
• Rule out balanoposthitis—preputial 
discharge, erythema of preputial or penile 
mucosa, and licking of prepuce.
• Rule out prostatitis, prostatic abscess, or 
prostatic neoplasia—urethral discharge, prostatomegaly, pyrexia, depression, dysuria, 
tenesmus, caudal abdominal pain, and stiff gait.
• Rule out urethritis, urethroliths, urethral 
neoplasms—dysuria, pollakiuria, stranguria, or 
palpable uroliths or mass lesions in the urethra.
• Rule out inflammatory disorders of urinary 
bladder and kidneys.
Specimens Collected by Cystocentesis
• Rule out urethral obstruction—stranguria, 
anuria, and a large overdistended urinary 
bladder.
• Rule out prostatic and urethral disorders 
(see above); purulent prostatic or urethral 
exudates can reflux into the urinary bladder.
• Rule out cystitis, urocystoliths, and urinary 
bladder neoplasia—dysuria, pollakiuria, 
stranguria, and/or palpable uroliths or mass 
lesions in the urinary bladder.
• Rule out pyelonephritis—pyrexia, depression, 
anorexia, polyuria, polydipsia, renal pain, and 
• Rule out post-traumatic pyuria—history of 
trauma, including iatrogenic causes.
• WBCs lyse rapidly in hypotonic or alkaline 
urine. Administration of alkalinizing agents 
or agents that produce hypotonic urine may 
falsely decrease urine WBC numbers.
• Leukocyte esterase reagent strip (dipstick) is 
not recommended for evaluating canine and 
feline urine. Nitrofurantoin, cephalosporins, 
and gentamicin can cause false-positive 
leukocyte esterase reactions.
• Urinary WBC concentrations can be low in 
patients with inflammatory disorders who 
have been given steroidal or nonsteroidal 
anti-inflammatory drugs.
Results
• Disorders with diminished WBC function 
or absolute neutropenia can artificially lower 
WBC values.
• Disorders with production of hypotonic urine 
or alkaline urine artificially lower WBC values.
Miscellaneous Factors That May Alter 
Dipstick (leukocyte esterase reaction) testing 
may result in false-negative results in dogs 
and both false-positive and false-negative 
results in cats.
Valid if urinary sediment is examined 
microscopically; invalid if only leukocyte 
esterase reagent strip (dipstick) method is used.
• Pyuria in specimens collected by voiding, 
manual compression, or transurethral 
catheterization indicates an inflammatory lesion 
involving at least the urinary or genital tracts.
• Pyuria in specimens collected by cystocentesis 
localizes the site of inflammation to at least the Pyuria

Canine and Feline, Seventh Edition  1175
Purinary tract, but does not exclude the urethra 
and genital tract. Reflux of prostatic exudates 
into the urinary bladder may result in pyuria in 
patients with prostatic disease.
• Pyuria with WBC casts is evidence of renal 
parenchymal inflammation.
• Generalized renal injury may be associated 
with concomitant leukocytosis, isosthenuria, 
and azotemia.
• Pyuria associated with bacteria, fungi, or 
parasite ova in sufficient numbers indicates 
that the inflammatory lesion was caused or 
complicated by urinary tract infection (UTI).
• Pyuria associated with neoplastic cells 
indicates neoplasia. Diagnosis of urinary tract 
neoplasia by cytologic examination of urine may 
be complicated by epithelial cell hyperplasia and 
atypia caused by urinary tract inflammation or 
the physiochemical properties of urine.
• Perform quantitative urine culture on all 
patients with pyuria; it provides the most 
definitive means of identifying and 
characterizing UTI. The absence of pyuria 
does not rule out bacteriuria as patients with 
bacteriuria frequently do not have pyuria.
• Negative urine culture results suggest a 
noninfectious cause of inflammation (e.g., 
uroliths, neoplasia) or inflammation associated 
with UTI caused by fastidious organisms (e.g., 
mycoplasmas and viruses) or by organisms 
capable of forming intracellular bacterial 
colonies or biofilms. False-negative culture 
results may also be due to recent antimicrobic 
therapy, sample mishandling, or delays 
between specimen collection and culture.
• Cytologic evaluation of urinary sediment, 
prostatic fluid, urethral or vaginal discharges, or 
biopsy specimens obtained by catheter or needle 
biopsy may help evaluate patients with localized 
urinary or genital tract disease. Cytologic exam  - 
ination may establish a definitive diagnosis of 
urinary tract neoplasia, but negative cytologic 
findings do not rule out neoplasia.
IMAGING
Abdominal radiography, contrast urethrocysto -
graphy, urinary tract ultrasonography, and 
excretory urography are important means of 
identifying and localizing underlying causes.
• Urethrocystoscopy—indicated in patients 
with persistent lesions of the lower urinary 
tract for which a definitive diagnosis has not 
been established by other, less invasive, means.
• Microscopic evaluation of tissue specimens—  
indicated in patients with lesions of the 
urinary or genital tracts for which a definitive diagnosis has not been established by other, 
less invasive, means; tissue specimens may be 
obtained by traumatic catheterization biopsy, 
cystoscopy and forceps biopsy, or exploratory 
laparotomy; aspiration and punch biopsy 
techniques may be used to evaluate the 
prostate gland.
  TREATMENT
• T reatment varies, depending on the under- 
 lying cause and specific organs involved.
• Pyuria associated with systemic signs of 
illness (i.e., pyrexia, depression, anorexia, 
vomiting, dehydration, leukocytosis, polyuria, 
and polydipsia) or urinary obstruction 
warrants aggressive diagnostic evaluation and 
initiation of specific, supportive, and/or 
• Avoid glucocorticoids or other immuno -
suppressive agents in patients suspected of 
having urinary or genital tract infection.
• Avoid potentially nephrotoxic drugs in 
febrile, dehydrated, or azotemic patients and 
those suspected of having pyelonephritis, 
septicemia, or preexisting renal disease.
  FOLLOW-UP
Response to treatment by serial urinalyses, 
including examination of urine sediment; collect 
specimens from most patients by cystocentesis 
to avoid contamination by preputial or vaginal 
exudates; perform transurethral catheterization 
if the expected benefits outweigh the risk of 
iatrogenic bacterial UTI.
• Infectious and noninfectious inflammatory 
disorders of the urinary tract can cause renal 
failure, urinary obstruction, uremia, 
septicemia, and death.
• Pyuria is a potential risk factor for 
formation of matrix or matrix-crystalline 
urethral plugs and subsequent urethral 
obstruction in male cats.  MISCELLANEOUS
SYNONYMS
Leukocyturia.
SEE ALSO
Adams LG. Ureteral disorders. In: Ettinger 
SJ, Feldman EC, Cote E, eds., Textbook of 
Louis, MO: Elsevier, 2017, pp. 1985–1991.
Forrester SD, Kruger JM, Allen TA. Feline 
lower urinary tract diseases. In: Hand MS, 
Thatcher CD, Remillard RL, et al., eds. 
Small Animal Clinical Nutrition, 5th ed. 
Topeka, KS: Mark Morris Institute, 2010, 
pp. 925–976.
Kutzler MA. Prostatic diseases. In: Ettinger 
Veterinary Internal Medicine, 8th ed. 
St. Louis, MO: Elsevier, 2017, 
pp. 2031–2036.
Osborne CA, Stevens JB, Lulich JP , et al. 
A clinician’s analysis of urinalysis. In: 
Osborne CA, Finco DR, eds., Canine and 
Feline Nephrology and Urology, 2nd ed. 
Baltimore, MD: Williams & Wilkins, 1995, 
pp. 136–205.
Phillips J. Neoplasia of the lower urinary tract. 
In: Bartges J, Polzin DJ, eds., Nephrology 
and Urology of Small Animals. Chichester, 
UK: Wiley-Blackwell, 2011, pp. 797–808.
A. Osborne, and Cheryl L. Swenson.(continued)  Pyuria

1176  Blackwell’s Five-Minute Veterinary Consult  
QQ Fever
  BASICS
OVERVIEW
• Caused by the zoonotic rickettsia Coxiella 
burnetii .
• Infection—most commonly by inhalation 
or ingestion of organism via infected body 
fluids (parturient discharges, urine, milk, or 
feces), tissues (especially placenta), or 
carcasses of infected animal reservoir hosts 
(cattle, sheep, goats); can occur after tick 
exposure (many species of ticks implicated).
• Lungs—thought to be main portal of entry 
to systemic circulation.
• Organism replicates in vascular endothe-
lium; causes widespread vasculitis; vasculitis 
results in necrosis and hemorrhage in lungs, 
liver, and CNS; severity depends on the 
pathogenicity of the strain of organism and 
host immune response.
• An extended latent period exists after 
recovery until chronic immune-complex 
phenomena develop; organism reactivated out 
of the latent state during parturition, resulting 
in large pathogen load in placenta, parturient 
fluids, urine, feces, and milk.
• Endemic in mammals worldwide; most 
cases in the United States in western states.
Cats and dogs of any age, sex, or breed.
SIGNS
• History of contact with farm animals or 
ticks.
• Fever.
• Abortion—especially cats.
• Ataxia and seizures—especially dogs.
• Splenomegaly often only clinical finding.
• Multifocal neurologic abnormalities—dogs.
• Coxiella burnetii .
• Exposure to infected animals (especially 
following parturition) and ticks.
  DIAGNOSIS
• Cats—other causes of abortion: infections 
(viral rhinotracheitis, panleukopenia, feline 
leukemia virus, toxoplasmosis; bacteria 
including coliforms, streptococci, staphylococci, 
salmonellae); fetal defects; maternal problems (nutrition, genital tract abnormalities); 
environmental stress; endocrine disorders.
• Dogs—canine parvovirus, canine distemper, 
other causes of encephalitis.
Serology and PCR
• Serology (immunofluorescence or ELISA)—a 
four-fold increase in IgG titer over a 4-week 
period is diagnostic; utility of increased IgM 
titer in a single sample is not well documented 
in small animals; crossreactivity with Bartonella  
species is possible.
• PCR—used to detect organisms in tissue 
culture or tissue specimens (e.g., placenta); 
whole blood can also be tested during 1st 
week of acute infection but negative blood 
PCR does not rule out infection.
IMAGING
N/A
Organism not detected on routine blood 
cultures; organism isolation may be 
performed by qualified laboratories.
  TREATMENT
• Alert client of possible zoonotic risk.
• Inpatient—avoids zoonotic risk to client
• Wear personal protective equipment 
(gloves, gown, mask, eye shield) when 
treating an infected animal or when attending 
an aborting cat.
• Isolate aborting and postpartum animals.
• Survives long periods in environment; 
inactivated by 5% hydrogen peroxide.
• Tetracycline 22 mg/kg PO q8h for 2 weeks.
• Doxycycline 10 mg/kg PO q12h for 1 week.
• Enrofloxacin 10–20 mg/kg PO q24h (dogs 
only) for 1 week; should be effective but no 
clinical reports; effective in vitro .
• Tetracycline drugs are associated with 
yellowing of teeth in young animals; do not 
use in animals with renal failure.
• Doxycycline may cause esophagitis and 
• Enrofloxacin may cause cartilage defects in 
young animals at high doses.
• Enrofloxacin may cause retinal degenera -
tion in cats.  FOLLOW-UP
• Difficult to determine success of therapy 
because many animals spontaneously 
improve.
• Even asymptomatic cases should be 
aggressively treated because of the zoonotic 
• Utility of predicting success of therapy 
based on serologic improvement unknown.
• Major zoonotic potential.
• Humans contract the disease by inhaling 
infected aerosols (e.g., after parturition); 
children commonly infected from ingesting 
raw milk but are usually asymptomatic.
• By the time a diagnosis is made in a pet, 
human exposure and infection have usually 
occurred.
• Instruct owners and people in contact with 
the pet to seek medical advice immediately.
• Previous urban outbreaks have been related 
to exposure to infected cats.
• Incubation period from time of contact 
until the first signs of illness is 5–32 days.
• Person-to-person transmission possible.
Sykes JE, Norris JM. Coxiellosis and Q fever. 
Infectious Diseases. St. Louis, MO: 
Saunders Elsevier, 2014, pp. 320–325.

Canine and Feline, Seventh Edition  1177
Q  BASICS
OVERVIEW
• CSF-filled diverticula within the subarachnoid 
space at the quadrigeminal cisterna (dorsal to the 
midbrain and adjacent to the third ventricle). 
More recently the term supracollicular fluid 
accumulation (SFA) has been used to described 
the anatomical location of the condition. CSF 
may be secreted by the arachnoid cells lining the 
cyst cavity. It is suspected that an anomaly of 
CSF flow from the choroid plexus during the 
stage of development forces a separation within 
the arachnoid layer. •  Clinical signs may 
develop as a result of gradual expansion of the 
subarachnoid space by a valve mechanism 
associated with pulsating CSF flow. •  May be 
an incidental finding.
Mainly in small breeds and brachycephalic 
patients—shih tzu, Maltese, pug, cavalier 
King Charles, Yorkshire terrier, Lhasa apso, 
Chihuahua, Pekingese, Pomeranian and 
bulldog.
Mean—5 years; range—2 months–10 years.
SIGNS
• Seizures. •  Abnormal behavior. •  If 
associated with hydrocephalus, could manifest 
with disorientation, behavioral changes, cortical 
blindness, compulsive circling, head pressing.
• Disturbance of embryogenesis where 
splitting of the primitive arachnoid membrane 
leads to fluid accumulation. •  Inflammatory 
conditions affecting the meninges. 
• Postsurgical trauma (intervertebral disc 
disease, spinal tumor). •  Neoplasia and 
hemorrhage. •  Intracystic hemorrhage 
secondary to trauma may result in expansion 
of the cyst and subsequent compression of the 
adjacent brain parenchyma.
  DIAGNOSIS
• Primary intracranial cyst-like lesions include 
intra-arachnoid, epidermoid, dermoid and 
choroid plexus cysts. •  Congenital brain 
anomalies (anencephaly, hydrocephalus, 
other). •  Storage disease. •  Infectious 
inflammatory diseases—viral (distemper virus, 
other viruses); fungal ( Blastomyces dermatitidis , 
Coccidioides  spp., Cryptococcus neoformans ); 
ricketssial ( Rickettsia rickettsii ); bacterial (Ehrlichia  spp., Escherichia coli , Streptococcus ); 
breed-related encephalitis (necrotizing 
encephalitis of the Yorkshire terrier, Maltese, 
and pug). •  Brain tumor—meningioma, 
glioma, choroid plexus papilloma, lymphoma.
IMAGING
• The prevalence of SFAs was 2.19% among 
CT studies ( n = 4,427) and 2.2% among 
MRI studies ( n = 626). •  MRI—extra-axial 
CSF-filled cyst at the quadrigeminal cisterna. 
On T1-weighted images, the lesion is hypo  - 
intense to brain tissue and isointense to CSF . 
On T2-weighted images, the lesion is 
hyperintense to brain tissue and isointense to 
CSF . On fluid attenuated inversion recovery 
(FLAIR) sequences, the cyst is hypointense, 
confirming the presence of CSF . Dilation of 
the ventricular system may be present if the 
cyst is obstructing CSF flow.
CSF—rule out concomitant inflammation. If 
CSF inflammatory, the cyst may be an 
  TREATMENT
• Medical therapy to control seizures and 
reduce CSF production. •  If signs are 
progressive, surgical cyst fenestration through 
craniotomy or craniectomy can result in 
clinical improvement. When hydrocephalus is 
present, surgical shunting can be considered. 
Other disease process must be ruled out before 
considering surgery. The cystic structure may 
be an incidental finding. •  Stable patients can 
be discharged with recommended medical 
therapy. •  Sequential assessment of pupillary 
helpful to determine risk of brain herniation.
• Glucocorticosteroids—dexamethasone 0.1 
mg/kg IV or PO q24h for 3 days followed by 
prednisone 0.25–0.5 mg/kg PO q24h for 10 
days, then reassess response and adjust dose. 
To prevent gastrointestinal ulceration, add 
omeprazole 0.5 mg/kg PO q24h or 
famotidine 0.5–1 mg/kg IV or PO q12h to 
steroid therapy. •  Antiepileptic drugs—
phenobarbital 2 mg/kg IV or PO q12h, 
levetiracetam 20 mg/kg PO q8–12h, or 
zonisamide 5–10 mg/kg PO q12h. 
• Diuretic—acetazolamide 10 mg/kg q6–8h 
as a carbonic anhydrase inhibitor that may help reduce CSF production and intracranial 
pressure. Omeprazole may act as an agent to 
reduce CSF production and provide gastric 
protection during steroid therapy.
The combination of glucocorticosteroid and 
diuretic may cause marked dehydration and 
increased blood viscosity that can result in poor 
cerebral perfusion and neurologic deterioration.
  FOLLOW-UP
(every 2–4 weeks). •  Corticosteroid may be 
necessary for a long period or for life. The goal 
is to find the dose that keeps the clinical signs 
controlled with minimal side effects. •  Evaluate 
phenobarbital levels after 4–5 weeks of starting 
therapy. •  If phenobarbital is continued, 
recheck biochemical profile and bile acids to 
assess hepatic function every 6 months.
• Prognosis is variable depending on severity of 
clinical signs and response to therapy. 
• Quadrigeminal cyst may be incidental or may 
result in progressive neurologic deterioration.
Hydrocephalus
• SFA = supracollicular fluid accumulation.
• IVIS: http://www.ivis.org •  VIN: http://
www.vin.com
Bertolini G, Ricciardi M, Caldin M. 
Multidetector computed tomographic and 
low-field magnetic resoance imaging 
anatomy of the quadrigeminal cistern and 
characterization of supracollicular fluid 
accumulation in dogs. Vet Radiol 
Ultrasound 2016, 57(3)259–268.
Platt S, Hicks J, Matiasek L. Intracranial 
intra-arachnoid diverticular and cyst-like 
abnormalities of the brain. Vet Clin North 
Am Small Anim Pract 2016, 46(2)253–263.
Author  Carolina DuqueQuadrigeminal Cyst

1178  Blackwell’s Five-Minute Veterinary Consult  
R  BASICS
A severe, fatal, viral polioencephalitis of 
warm-blooded animals, including humans.
Virus—enters body through a wound (usually 
from a bite of rabid animal) or via mucous 
membranes, replicates in myocytes, spreads to 
the neuromuscular junction and neuro -
tendinal spindles, travels to the central 
nervous system (CNS) via intra-axonal fluid 
within peripheral nerves, spreads throughout 
the CNS; finally spreads centrifugally within 
peripheral, sensory, and motor neurons.
• Nervous—brain, spinal cord, ± peripheral 
nervous system (PNS).
• Salivary glands—contain large quantities of 
infectious virus particles that are shed in 
saliva.
GENETICS
None
• Incidence of disease within infected 
animals—high (approaches 100%).
• Prevalence—overall low; can be significant 
in enzootic areas; especially high in countries 
where vaccination of dogs and cats is not 
routine.
• Worldwide.
• Exceptions—New Zealand, Hawaii, Japan, 
Iceland, and parts of Scandinavia.
• Species-adapted strains—specific geographic 
distributions within endemic countries.
Species
• All warm-blooded mammals, including 
dogs, cats, and humans.
• United States—five strains endemic within 
fox, raccoon, skunk, coyote, and insectivorous 
bat populations; all five strains can be 
transmitted to dogs and cats.
None
All ages, but animals that come in contact 
with wildlife at highest risk.
None
SIGNS
• Variable; atypical presentation is the rule 
rather than the exception.
• Can present with focal or multifocal signs 
affecting either brain, spinal cord, PNS, or 
any combination.• Three classical progressive stages of disease 
 ◦Prodromal—mentation change (more 
docile or more agitated) ± fever.
 ◦Furious—prosencephalon signs including 
hyperactivity, aggression, seizures ± ataxia; 
90% of rabid cats have furious form.
 ◦Paralytic—lower motor neuron (LMN) 
paresis or paralysis starting near site of 
inoculation then spreading through nervous 
system; paralytic form can follow furious 
form, especially in cats.
• Mentation/behavior change—variable; can 
include unusual shyness, excitability, aggression.
• Gait change—lameness, ataxia, paralysis.
• Licking or chewing at site of inoculation, 
although wound not always identified.
• Change in tone of bark.
• Excess salivation or frothing at the mouth.
• All or some of the historical findings
• Fever.
• Cranial nerve deficits—myosis, anisocoria, 
absent pupillary light reflex (PLR); dropped 
jaw; absent gag reflex (assess by compressing 
larynx and avoid hand in mouth if rabies 
suspected).
CAUSES
Rabies virus—a single-stranded, enveloped, 
bullet-shaped RNA virus; genus Lyssavirus ; 
family Rhabdoviridae .
• Exposure to wildlife, especially skunks, 
raccoons, bats, and foxes.
• Inadequate vaccination against rabies.
• Bite or scratch wounds from unvaccinated 
dogs, cats, or wildlife.
• Exposure to aerosols in bat caves.
• Immunocompromised animal—use of 
modified live virus rabies vaccine.
  DIAGNOSIS
• Must seriously consider rabies for any dog 
or cat showing acute behavior change or 
unaccountable neurological signs, especially 
those not previously vaccinated for rabies. 
Caution: handle with considerable care to 
prevent possible transmission of the virus to 
individuals caring for or treating the animal.
• Acute, progressive CNS and/or PNS 
disease—infectious (e.g., viral encephalitis 
or myelitis), immune-mediated (e.g., 
granulomatous or necrotizing meningo -
encepalitis, necrotizing leukoencephalitis, 
polymyositis), metabolic (e.g., hepatic encephalopathy, hypoadrenocorticism), 
neoplastic, degenerative.
No characteristic hematologic or biochemical 
changes.
N/A
IMAGING
N/A
• There are no definitive premortem 
diagnostics. Diagnostics performed on rabies 
suspects should be done with extreme caution 
to prevent exposure to infective tissues. 
Consider consultation with a neurologist.
• Direct immunofluorescent antibody (DFA) 
test of nervous tissue—rapid and sensitive; 
collect head or entire body following death or 
euthanasia, chill sample immediately. Submit 
to a state-approved laboratory for rabies 
diagnosis. Caution: use extreme care when 
collecting, handling, and shipping these 
specimens to prevent exposure of 
veterinarians, staff or handlers.
• DFA test of dermal tissue—skin biopsy of 
the sensory vibrissae of the maxillary area, 
including deeper subcutaneous hair follicles; 
approved for human diagnostics, but not for 
animal diagnostics; accurate if positive, but 
negative test does not rule out rabies.
• Rabies antibody titer—a serologic antibody 
titer of 0.5 IU/mL is considered adequate for 
protection in vaccinated people and animals. In 
most states in the United States, titers are not 
considered a legal replacement for vaccination.
• Gross changes—generally absent.
• Histopathologic changes—acute to chronic 
polioencephalitis; gradual increase in the 
severity of the nonsuppurative inflammatory 
process in the CNS as disease progresses; large 
neurons within the brain may contain classic 
intracytoplasmic inclusions (Negri bodies).
  TREATMENT
Strictly inpatient.
Administer with extreme caution.
ACTIVITY
• Confine to secured quarantine area with 
clearly posted signs indicating suspected 
rabies.
• Runs or cages should be locked; only 
designated people should have access.
• Feed and water without opening the cage or 
run door.Rabies

Canine and Feline, Seventh Edition  1179
RDIET
Soft, moist food; most patients will not eat.
• Thoroughly inform client of the seriousness 
of rabies to the animal and the zoonotic 
• Ask client about any human exposure (e.g., 
contact, bite) and strongly urge client to see a 
physician immediately.
• Local public health official must be notified.
• Skin biopsy—may help establish antemortem 
diagnosis; must be confirmed by 
identification from CNS tissue.
• No treatment.
• Once the diagnosis is likely, euthanasia is 
None
N/A
N/A
N/A
  FOLLOW-UP
• All suspected rabies patients should be 
securely isolated and monitored for any 
development of mood change, attitude 
change, or clinical signs that might suggest 
the diagnosis.
• An apparently healthy dog or cat that bites 
or scratches a person should be monitored for 
a period of 10 days; if no signs of illness occur 
in the animal within 10 days, the person has 
had no exposure to the virus; dogs and cats 
do not shed virus for more than 3 days before 
development of clinical disease.• An unvaccinated dog or cat that is bitten or 
exposed to a known rabid animal must be 
quarantined according to local or state 
regulations, often for up to 6 months.
• Vaccines (dogs and cats)—vaccinate 
according to standard recommendations and 
state and local requirements; all dogs and cats 
with any potential exposure to wildlife or 
other dogs; vaccinate after 12 weeks of age, 
then 12 months later, then every 3 years 
using a vaccine approved for 3 years; use only 
inactivated or recombinant vector vaccines 
for cats.
• Vaccinated animals exposed to possible or 
confirmed rabies suspect should receive 
booster vaccine, according to applicable 
local laws.
• Rabies-free countries—entering dogs and 
cats are quarantined for long periods, usually 
6 months.
• Disinfection—any contaminated area, cage, 
food dish, or instrument must be thoroughly 
disinfected; use a 1:32 dilution (4 ounces/
gallon) of household bleach to quickly 
inactivate the virus.
• Development of acute neurological signs, 
death.
• Difficulty of antemortem diagnosis my lead 
to humans and other animals being exposed 
to virus.
• Prognosis—grave; almost invariably fatal.
• Dogs and cats with clinical infection usually 
succumb within 1–10 days of onset of clinical 
signs; often within 3–4 days.
None
None
• Extreme.
• Humans must avoid bites and contact with 
saliva or CNS tissue from a rabid animal or an asymptomatic animal that is incubating 
• Suspected rabies cases must be strictly 
quarantined and confined to prevent exposure 
to humans and other animals. Full personal 
protective equipment should be worn if 
interaction is necessary.
• Local and state regulations must be adhered 
to carefully and completely.
Infection during pregnancy is fatal to dam.
SYNONYMS
N/A
• CNS = central nervous system
• DFA = direct immunofluorescent  
antibody.
www.cdc.gov/rabies/
Brown CM, Slavinski S, Ettestad P , et al. 
Compendium of animal rabies prevention 
and control, 2016. J Am Vet Med Assoc 
2016, 248:505–517.
Frymus T, Addie D, Belák S, et al. Feline 
rabies: ABCD guidelines on prevention and 
management. J Feline Med Surg 2009, 
11:585–593.
Greene CE. Rabies and other Lyssavirus 
167–183.
acknowledge the prior contribution of Fred 
W. Scott.
available online(continued)  Rabies

1180  Blackwell’s Five-Minute Veterinary Consult  
R  BASICS
OVERVIEW
• Eversion of one or more layers of the 
rectum through the anus.
• An anal prolapse (incomplete prolapse) is a 
protrusion of anorectal mucosa through the 
external anal orifice.
• A rectal prolapse (complete prolapse) is a 
double-layer invagination of the full thickness 
of the rectal tube through the anal orifice.
• Dog and cat (especially Manx).
• Any age, sex, or breed.
• High prevalence for young, parasitized dogs 
or cats with diarrhea.
SIGNS
• Persistent tenesmus.
• Incomplete prolapse—protrusion of a 
portion of the circumference of the rectal 
mucosa that typically appears worse 
immediately after defecation and then 
subsides.
• Complete prolapse appears as a tubular 
hyperemic mass protruding from the anus.
• Chronic prolapses may be dark blue or 
black in color or the mucosa may be 
• Gastrointestinal disorders that cause 
diarrhea and tenesmus, such as parasitism, 
colitis/enteritis, constipation/obstipation, 
rectal foreign body, rectal deviation and 
diverticulum, proctitis, and rectal or anal 
tumors.
• Urogenital disorders, such as cystitis, 
urolithiasis, prostatitis, prostatic hypertrophy, 
and dystocia.
• Tenesmus following perineal, rectal, or 
urogenital surgery (e.g., perineal 
herniorrhaphy).
  DIAGNOSIS
• Prolapsed intussusception—rule out by 
passing a finger or blunt probe between the 
mass and the anus (the probe should not 
penetrate more than 1–2 cm before contacting 
the fornix; if the probe easily passes 5–6 cm, 
then suspect prolapsed intussusception) or by 
abdominal ultrasonography (look for 
increased intestinal layering).
• Neoplasia—rule out by palpation, 
fine-needle aspiration and cytology, and/or 
biopsy and histopathology.CBC/BIOCHEMISTRY/URINALYSIS
• Inflammatory or stress leukogram may be 
present.
Fecal examination may confirm parasitism.
IMAGING
usually unremarkable.
• Abdominal radiography—may demonstrate 
foreign body, prostatomegaly, cystic calculi, or 
colonic fecal distention.
demonstrate prostatomegaly, cystic calculi, 
bladder wall thickening, or intussusception.
• Rectal examination to palpate for perineal 
hernia.
• Colonoscopy may help evaluate recurrent 
prolapse for an underlying cause.
Assess viability of the prolapsed tissue by 
surface appearance and tissue temperature—
vital tissue appears swollen and hyperemic, 
and red blood exudes from the cut surface; 
devitalized tissue appears dark purple or 
black, and dark cyanotic blood exudes from 
the cut surface; ulcerations may be present.
  TREATMENT
• Must identify and treat underlying cause.
• Conservative medical management—gently 
replace prolapsed tissue through the anus with 
the use of lubricants (e.g., KY Jelly and gentle 
massage); osmotic agents (e.g., 50% dextrose 
solution) may help if severe swelling exists.
• Use of an epidural may facilitate treatment 
and relieve discomfort.
• Place a purse-string suture to aid retention 
and prevent acute recurrence; place the suture 
loose enough to allow room for defecation.
• Decrease straining with stool softeners.
• Colopexy recommended for recurrent 
viable prolapses or if straining persists after 
rectal resection and anastomosis.
• When prolapse is nonreducible and/or 
devitalized, rectal resection and anastomosis 
are necessary.
• Appropriate anesthetic/analgesics as needed.
• Appropriate perioperative antibiotics are 
recommended (e.g., cefoxitin sodium 30 mg/
kg IV) for resection and anastomosis.• Stool softeners—docusate sodium (dogs, 
50–200 mg PO q8–12h; cats, 50 mg PO 
q12–24h) or lactulose (10 g/15 mL solution 
or syrup, 1 mL/4.5 kg q8–12h to effect); 
continue for 2–3 weeks after removal of the 
purse-string suture.
• Anthelmintic based on fecal examination.
• Feed a low-residue diet until purse-string 
suture is removed.
N/A
  FOLLOW-UP
• Purse-string suture removal in 3–7 days.
• Examine for rectal stricture if straining 
persists following anastomosis.
• Recurrence—especially if underlying cause 
is not eliminated.
• Postoperative—may include infection, 
anastomosis dehiscence within 5–7 days 
postoperatively, or rectal stricture.
• Fecal incontinence after resection (sensory 
incontinence resulting from removal of 
receptors in rectal wall).
Intestinal parasitism.
SEE ALSO
Aronson LR. Rectum, anus, perineum. In: 
Tobias KM, Johnston SA, eds., Veterinary 
Small Animal Surgery. St. Louis, MO: 
Elsevier Saunders, 2012, pp 1564–1600.
Radlinsky MG. Rectal prolapse. In: Fossum 
TW, ed., Small Animal Surgery, 5th ed. 
Philadelphia: Elsevier, 2019, pp. 504–507.
Consulting Editor  Mark P . RondeauRectal and Anal Prolapse

Canine and Feline, Seventh Edition  1181
R  BASICS
OVERVIEW
• Diminution in the size of the rectal or anal 
lumen either from cicatricial contracture or 
scarring as a result of wound healing or 
chronic inflammation or from proliferative 
• Gastrointestinal function is compromised 
because of outflow obstruction.
• Any age, breed, or gender.
SIGNS
• Vary with severity.
• Hematochezia.
• Mucoid feces.
• Large bowel diarrhea.
• Secondary megacolon can develop.
• Inflammatory—rectoanal abscess, anal 
sacculitis, perianal fistulae, proctitis, 
histoplasmosis, pythiosis.
• T raumatic— foreign body, laceration.
• Neoplastic—rectal adenocarcinoma, 
leiomyoma, or polyps.
• Iatrogenic—rectal anastomosis, mass 
excision, or biopsy.
• Congenital—atresia ani.
  DIAGNOSIS
• Space-occupying processes that lead to 
diminished rectal capacity (extraluminal 
compression [e.g., prostatic disease, pelvic 
fractures], intraluminal obstruction [e.g., 
pseudocoprostasis, foreign body]) and 
functional constriction (muscle spasms).
• Differentiate by rectal palpation and imaging.
• May have an inflammatory leukogram.
N/A
IMAGING
• Survey abdominal radiography and contrast 
studies (e.g., barium, air, or double-contrast 
enema and barium gastrointestinal series) may 
reveal consistent narrowing of the rectal lumen.
thickening and altered architecture if infiltrative rectocolonic disease is present 
(e.g., pythiosis, neoplasia).
• Digital rectal palpation.
• Proctoscopy/colonoscopy to visualize 
stricture, determine extent, and procure 
biopsy specimens.
• Colonic scrapings may aid in cytologic 
diagnosis of fungal (histoplasmosis) and 
neoplastic diseases.
• Biopsy to classify the disease process and 
establish a prognosis.
  TREATMENT
• T reat the underlying cause when possible.
• Medical treatment for palliation (stool 
softeners/enemas) or the elimination of 
infective agents or inflammatory conditions.
• Fluid therapy to optimize hydration prior 
to administering an enema to constipated or 
obstipated patients.
• Anesthesia may be necessary for enema 
• Balloon dilation of non-neoplastic and 
postoperative strictures—multiple procedures 
• Surgical reconstruction of focal strictures 
(plasty procedures).
• Resection and anastomosis may be necessary 
for extensive lesions and recurrent strictures.
• Colorectal stent placement may relieve 
obstruction due to nonresectable neoplasms 
and non-neoplastic lesions.
• Radiotherapy and/or chemotherapy for 
some neoplasms.
• Stool softeners—docusate sodium; lactulose.
• Corticosteroids—prednisone to treat 
inflammatory conditions (0.5–1 mg/kg PO 
q24h or divided q12h) and after balloon 
dilation to prevent stricture recurrence. 
Intralesional injection of triamcinolone prior 
to dilatation may prevent recurrence.
• Chemotherapy or antifungal therapy if 
• Broad-spectrum perioperative antimicrobial 
therapy (e.g., cefoxitin sodium 30 mg/kg IV) 
with balloon dilation or surgical therapy.
• Antibiotics continued after dilation if 
mucosal tearing occurs.
• Corticosteroids when infection is possible.• Corticosteroids may slow healing after 
surgical correction.
  FOLLOW-UP
• Recurrence or metastasis of neoplastic lesions.
• Following balloon dilation patients should 
be reevaluated for stricture reformation 7–14 
days after the procedure to determine the 
need for additional dilation procedures.
• Medical treatment—can include inefficacy, 
diarrhea, and adverse effects of medications.
• Balloon dilation can result in deep rectal 
tears, hemorrhage, or possibly full-thickness 
perforation. Stricture recurrence is common 
following balloon dilation. Multiple dilations 
• Surgical treatment—fecal incontinence, 
secondary stricture formation, and wound 
dehiscence.
• Varies with the severity of the stricture.
• Patients with benign strictures that are 
readily managed medically or with balloon 
dilation or bougienage may have a good 
long-term outcome.
• Surgical resection has more guarded 
prognosis because of the frequency of 
• Most patients with recognizable clinical 
signs due to neoplasia have a guarded-to-poor 
prognosis for complete resolution.
Atresia ani is seen within weeks of birth.
SEE ALSO
• Rectoanal Polyps.
Elsevier Saunders, 2012, pp. 1564–1600.
Consulting Editor  Mark P . RondeauRectal Stricture

1182  Blackwell’s Five-Minute Veterinary Consult  
R  BASICS
OVERVIEW
Most rectoanal polyps are benign growths 
located in the distal rectum. Histopathologic 
evaluation typically reveals adenomas, but 
lesions may undergo malignant transformation.
• Dog and rarely cat. •  Middle-aged to older. 
• No breed or sex predilection established 
but German shepherd dogs, collies, and West 
Highland white terriers overrepresented in 
SIGNS
• May be none (incidental finding on 
wellness exam). •  Hematochezia with 
relatively well-formed feces. •  Mucus-covered 
feces. •  Pencil-thin or ribbon-like feces. 
• Tenesmus. •  Dyschezia. •  Soft, well-
vascularized, friable, and often ulcerated 
mass(es) may be seen or palpated rectally. 
• Usually single but multiple polyps can 
occur. •  May be pedunculated or broad-
based sessile masses.
Unknown
  DIAGNOSIS
• Carcinoma in situ  and adenocarcinoma. 
• Other neoplasms—leiomyoma, 
lymphoma, papilloma. •  Inflammatory 
polyps—primarily reported in miniature 
dachshunds in Japan; lesions appear as 
diffuse small white polyps that are responsive 
to immunosuppressive therapy. •  Proctitis. 
• Pythiosis. •  Colitis (clinical signs are 
characterized by diarrhea with a marked 
increase in frequency, scant volume of feces, 
increased fecal mucus, and tenesmus. These 
clinical signs are vastly different to those of 
dogs with rectoanal polyps which do not 
cause diarrhea). •  Incomplete rectal 
prolapse.
N/A
IMAGING
N/A
• Rectal palpation. •  Direct visualization 
through anus. •  Proctoscopy—viable low-cost 
procedure that allows one to visualize the 
descending colon after cleansing the animal’s 
colon. This method is suitable in most dogs 
and cats because the polyps are usually localized to the rectoanal or colorectal region and tend 
not to metastasize. •  Colonoscopy—may be 
recommended to evaluate the entire rectum 
and colon for additional polyps but in a review 
of 82 cases, no lesions were found orad to the 
colorectal junction. •  Cytologic examination 
of polyp aspirate or scraping may help the 
initial diagnosis, although cytology should be 
interpreted with caution given the inherent 
challenges of differentiating benign adenomas 
from adenocarcinomas cytologically. 
• Histopathologic examination of excised 
tissue is required for definitive diagnosis and to 
assess completeness of the excision.
• Adenomatous polyp. •  Adenomatous 
hyperplasia. •  Carcinoma in situ .
  TREATMENT
• Surgical excision is the treatment of choice. 
• Most polyps can be exteriorized directly 
through the anus and removed with submucosal 
resection. •  Close the mucosal defect with 
absorbable sutures, avoiding compromise of the 
lumen diameter. •  Lesions that cannot be 
exteriorized may be removable transanally by 
electrosurgery with endoscopic guidance or can 
be directly exposed through a dorsal rectal 
approach. •  One study in dogs showed 
significant improvement in clinical signs 
following administration of piroxicam, but 
long-term follow-up is not available. Numerous 
nonsteroidal anti-inflammatory drugs (NSAIDs) 
have been evaluated in humans with mixed 
results (see Internet Resources).
kg IV). •  Stool softeners may help decrease 
tenesmus—docusate sodium (dogs, 50–200 
mg PO q8–12h; cats, 50 mg PO q12–24h) or 
docusate calcium (dogs, 50–100 mg PO 
q12–24h; cats, 50 mg PO q12–24h). 
• Alternative stool softener—lactulose 
(1 mL/4.5 kg PO q8h to effect).
N/A
  FOLLOW-UP
• Examine the excision site 14 days after 
surgery and again at 3 and 6 months to 
ensure absence of recurrence or stricture. • T wice yearly examination thereafter to 
assess for recurrence.
• Recurrence. •  Rectal stricture (rare).
• Dogs with focal single adenomas have a 
good prognosis with a low rate of recurrence. 
• Dogs with multiple and/or diffuse lesions 
(involvement of >50% of circumference of 
rectal wall) have much higher rates of 
recurrence. •  Malignant transformation of 
benign lesions can occur in up to 50% of 
dogs. •  Excised tissues should be submitted 
for histopathology even when preoperative 
biopsies have been performed. The diagnosis 
may change in up to one-third of the cases in 
which preoperative endoscopic biopsies are 
SEE ALSO
• Adenocarcinoma, Anal Sac.
• Dyschezia and Hematochezia. 
• Rectal and Anal Prolapse.
drug.
http://www.bandolier.org.uk/band129/
b129-6.html. This site reviews the mixed 
results of clinical trials using various NSAIDs 
in humans.
Consulting Editor  Mark P . RondeauRectoanal Polyps

Canine and Feline, Seventh Edition  1183
R  BASICS
Erythema of the eyelids, increased or 
hyperemic ocular surface vasculature, or 
hemorrhage within the eye.
• Active dilation of ocular vessels—in 
response to extraocular or intraocular 
inflammation or passive congestion.
• Hemorrhage from existing or newly formed 
Ophthalmic—eye and/or ocular adnexa.
SIGNS
• Depends on cause.
• May affect one or both eyes.
• Result of systemic disease—abnormalities 
in other organ systems common.
CAUSES
• Blepharitis.
• Keratitis.
• Episcleritis or scleritis.
• Hyphema.
• Orbital disease—usually the orbital 
abnormality is more prominent.
• Systemic infectious or inflammatory 
diseases.
• Irritation by potentially any topical 
ophthalmic medication.
• T rauma.
  DIAGNOSIS
More than one cause may occur 
• Rule out normal variations.
• Palpebral conjunctiva—normally redder 
than bulbar conjunctiva.
• One or two large episcleral vessels—may be 
normal if the eye is otherwise quiet.• T ransient mild hyperemia—with excite­
ment, exercise, and straining.
• Horner’s syndrome—may cause mild 
conjunctival vascular dilation; differentiated 
by other signs and pharmacologic testing.
Causes
• Superficial (conjunctival) vessels—originate 
near the fornix, move with the conjunctiva, 
branch repeatedly, and blanch quickly with 
topical 2.5% phenylephrine or 1:100,000 
epinephrine. Suggests ocular surface disorders 
(e.g., conjunctivitis, superficial keratitis, 
blepharitis).
• Deep (episcleral) vessels—originate near the 
limbus, branch infrequently, do not move 
with the conjunctiva, and blanch slowly or 
incompletely with topical sympathomimetics. 
Suggests episcleritis or intraocular disease 
(e.g., anterior uveitis or glaucoma).
• Discharge—mucopurulent to purulent: 
typical of ocular surface disorders and 
blepharitis; serous or none: typical of 
intraocular disorders.
• Swollen or inflamed eyelids—suggest 
blepharitis.
• Corneal opacification, neovascularization, 
or fluorescein stain retention—suggest 
• Aqueous flare or cell (increased protein or 
cells in the anterior chamber)—confirms 
diagnosis of anterior uveitis.
• Pupil—miotic: common with anterior 
uveitis; dilated: common with glaucoma; 
normal: with blepharitis and conjunctivitis.
• Abnormally shaped or colored irides—
suggest anterior uveitis.
• Luxated or cataractous lenses—suggest 
glaucoma or anterior uveitis.
• Intraocular pressure (IOP)—high: 
diagnostic for glaucoma; low: suggests 
• Loss of vision—suggests glaucoma, anterior 
uveitis, or severe keratitis.
• Glaucoma and anterior uveitis—may 
complicate hyphema.
Typically normal, except with anterior uveitis, 
glaucoma, or hyphema secondary to systemic 
disease.
Depends on cause—see specific types of red 
eye (conjunctivitis, uveitis, etc.).
IMAGING
• Chest radiographs—consider with anterior 
uveitis or if intraocular neoplasia is a 
possibility.
• Abdominal radiography or ultrasono­
graphy—may rule out infectious or neoplastic 
causes.
• Ocular ultrasonography—if the ocular 
media are opaque; may define the extent and 
nature of intraocular disease or identify intra  ­ 
ocular tumor.DIAGNOSTIC PROCEDURES
Tonometry—must perform in every patient 
with an unexplained red eye.
Ocular Surface Disorders
• Aerobic bacterial culture and sensitivity—
with a purulent discharge, chronic disease, or 
poor response to treatment.
• Schirmer tear test.
• Cytologic examination of affected tissue.
• Cats—consider PCR or immunofluorescent 
antibody (IFA) test on corneal or conjunctival 
scrapings for feline herpesvirus and Chlamydia ; 
collect sample before fluorescein staining to 
avoid false ­positive results on IFA.
• Fluorescein stain.
• Conjunctival biopsies—with chronic 
conjunctivitis or with a mass lesion.
• See specific disease—Conjunctivitis—Cats, 
Conjunctivitis—Dogs; Blepharitis; Keratitis 
chapters.
Intraocular Disorders
• See specific disease: Anterior Uveitis—Cats; 
Anterior Uveitis—Dogs; Hyphema; Glaucoma.
  TREATMENT
• Elizabethan collar—to prevent self ­trauma
• Avoid dirty environments or those that may 
lead to ocular trauma, especially if topical 
corticosteroids are used.
• Because there is a narrow margin for error, 
consider referral if the diagnosis is uncertain 
and/or glaucoma cannot be ruled out.
• Few causes are fatal; however, a workup 
may be indicated (especially with anterior 
uveitis and hyphema) to rule out potentially 
fatal systemic diseases.
• Deep corneal ulcers and glaucoma—may be 
• Depends on specific cause.
• Generally, control ocular pain, inflammation, 
infection, and IOP .
• Carprofen 2.2 mg/kg PO q12h or 4.4 mg/
kg PO q24h to control mild inflammation 
and reduce pain
• Topical corticosteroids—contraindicated if 
the cornea retains fluorescein stain.
• Systemic corticosteroids—avoid until 
infectious systemic causes have been ruled out.Red Eye

1184  Blackwell’s Five-Minute Veterinary Consult  
RPRECAUTIONS
• Topical aminoglycosides—may be 
irritating; may impede reepithelization if used 
frequently or at high concentrations.
• Topical solutions—may be preferable to 
ointments if corneal perforation is possible.
• Atropine—may exacerbate 
keratoconjunctivitis sicca (KCS) and glaucoma.
(NSAIDs)—use with caution in hyphema.
N/A
N/A
  FOLLOW-UP
required to ensure that IOP , ocular pain, and 
inflammation are well controlled.• The greater the risk of loss of vision, the 
more closely the patient needs to be followed; 
may require daily or more frequent 
• Loss of the eye or permanent vision loss.
• Chronic ocular inflammation and pain.
• Death.
Numerous systemic diseases.
N/A
Systemic corticosteroids may complicate 
SEE ALSO
• Anterior Uveitis—Cats.• Conjunctivitis—Dogs.
drug.
Elsevier, 2018.
available onlineRed Eye  (continued)

Canine and Feline, Seventh Edition  1185
R  BASICS
Passive, retrograde movement of undigested 
gastric or esophageal contents into the oral 
cavity. Reflux refers to the retrograde 
movement of gastric juice across the gastro  - 
esophageal sphincter into the esophagus.
Regurgitation results from a loss of normal 
esophageal motility. In the normal esophagus, 
the presence of a food bolus in the proximal 
esophagus stimulates afferent sensory 
neurons. Signals are transferred centrally, via 
the vagus and glossopharyngeal nerves, to the 
tractus solitarius and nucleus ambiguus. 
Motor impulses travel back via the vagus 
nerve to stimulate striated muscle (canine) 
and striated and smooth muscle (feline) to 
cause esophageal peristalsis. Lesions anywhere 
along this pathway may lead to regurgitation. 
Esophagitis secondary to reflux can cause 
esophageal dysmotility and subsequent 
regurgitation. Delayed gastric emptying is a 
common and underappreciated cause of 
reflux and possible regurgitation.
• Gastrointestinal—dysphagia, weight loss. 
• Musculoskeletal—weakness, weight loss. 
• Nervous—polyneuropathies, CNS disease. 
• Respiratory—aspiration pneumonia.
GENETICS
• Regurgitation due to megaesophagus 
can be inherited in smooth fox terriers 
(autosomal recessive) and miniature 
schnauzers (autosomal dominant or 60% 
penetrance autosomal recessive). In 
addition, Jack Russell terriers, springer 
spaniels, long-haired miniature dachshunds, 
golden retrievers, Labrador retrievers, and 
Samoyeds are predisposed to the congenital 
form of myasthenia gravis. A breed predis -
position for acquired megaesophagus also 
exists for the German shepherd dog, Great 
Dane, Irish setter, Labrador retriever, pug, 
and Chinese Shar-Pei. The site and 
patho  genesis of the lesion in idiopathic 
megaeso  phagus is unknown. Suggested 
hypotheses include abnormalities of the 
afferent limb of the reflex arc (receptors, 
neurons) or of the swallowing center in the 
CNS. •  Boxers and Newfoundlands have a 
genetic predisposi  tion for inflammatory 
myopathy that is associated with esophageal 
dysmotility. •  Brachycephalic breeds are 
predisposed to sliding hiatal hernias (type I) 
that is typically associated with gastro -
esophageal reflux and regurgitation.
N/A
Species
Dog (more commonly) and cat.
• Smooth fox terriers, miniature schnauzers. 
Other predisposed breeds include Great 
Dane, German shepherd dog, Irish setter, 
Labrador retriever, Newfoundland, and boxer, 
brachycephalic breeds (shar-pei, pug, Boston 
terrier, English bulldog, French bulldog). 
• Siamese and Siamese-related cats.
• Congenital cases present soon after birth 
(congenital megaesophagus) or at weaning 
(vascular ring anomalies) during the 
transition from liquid diet to solid foods. 
• Acquired cases may be seen at any age, 
depending on the etiology.
No gender predilection has been identified.
SIGNS
• Clients often report vomiting; the 
regurgitation using a comprehensive history. 
Having owner videotape events may be 
helpful. •  Regurgitation—passive process; 
little to no abdominal effort; no prodromal 
phase; regurgitated material has increased 
amounts of thick mucus. •  Vomiting—active 
process; prodromal phase is identified; 
vomited material may have increased amounts 
of bile staining. •  The shape of the expelled 
material (i.e., tube-like), presence of 
undigested food, and length of time from 
ingestion to regurgitation or vomiting are less 
helpful to differentiate.
• Vomiting (as perceived by owner). 
• Dysphagia. •  Coughing. •  Ravenous 
appetite. •  Weight loss. •  Ptyalism. •  Other 
signs, depending upon underlying etiology.
• Cervical swelling may be noted. •  Ptyalism. 
• Halitosis. •  Increased respiratory noises. 
• Nasal discharge and fever (if concurrent 
pneumonia). •  Cachexia. •  Weakness.
CAUSES
Congenital Pharyngeal or 
Pharyngoesophageal
• Cleft or short palate (typically associated 
with nasal reflux). •  Cricopharyngeal muscle 
achalasia (typically associated with nasal 
reflux and dysphagia). •  Myasthenia gravis.
Congenital Esophageal
• Vascular ring anomaly (e.g., persistent right 
aortic arch). •  Megaesophagus. •  Glycogen 
storage disease. •  Esophageal diverticulum. 
• Bronchoesophageal fistula.
Acquired Pharyngeal or 
• Cricopharyngeal dysphagia. •  Foreign 
bodies. •  Neoplasia. •  Rabies. •  Toxicity (botulism). •  Myopathy/neuropathy/
junctionopathy.
Acquired Esophageal
• Megaesophagus. •  Myasthenia 
gravis. •  Stricture. •  Neoplasia. 
• Hypoadrenocorticism. •  Hypothyroidism. 
• Hiatal hernia. •  Dysmotility. 
• Gastroesophageal intussusception. 
• Gastroesophageal reflux. •  Periesophageal 
masses. •  Dysautonomia. •  Myopathy/
neuropathy. •  Foreign bodies. •  Granulo -
matous disease. •  Toxicity (lead). •  Idiopathic. 
• Gastric dilatation/volvulus. •  Parasitic 
infection ( Spirocerca lupi ). • Broncho -
esophageal fistula.
Congenital or Acquired Gastric (Increase 
Gastroesophageal Reflux)
• Pyloric outflow obstruction. •  Gastric 
foreign body. •  Gastric hypomotility.
• Increased risk of gastroesophageal reflux 
with general anesthesia; the resultant 
esophagitis may lead to stricture formation 
and regurgitation. •  Administration of 
doxycycline or clindamycin have been 
associated with esophagitis and stricture 
formation. •  Esophageal foreign body. 
• Swallowing caustic agents causing 
  DIAGNOSIS
• Regurgitation is a clinical sign, not a 
diagnosis, and is the hallmark of esophageal 
disease. •  It is important to differentiate 
vomiting from regurgitation.
• There are no pathognomonic changes for 
regurgitation. •  Inflammatory leukogram 
may be seen if aspiration pneumonia is 
present. •  Most helpful for evaluation of 
possible underlying etiologies: e.g., erythro -
cyte changes with lead toxicosis, elevated 
creatine kinase (CK) with myopathy, 
hypoadrenocorticism, hypercholesterolemia 
These elucidate etiologies of acquired 
conditions causing regurgitation and include 
stimulation test or baseline cortisol level 
(hypoadrenocorticism); thyroid serology 
(hypothyroidism); acetylcholine receptor 
antibody level (myasthenia gravis); blood lead 
levels (toxicosis).
IMAGING
• Thoracic and cervical radiography—evidence 
of a gas-, fluid-, or ingesta-filled esophagus 
with megaesophagus; may also show aspiration 
pneumonia, neoplasia, foreign bodies, hiatal Regurgitation

1186  Blackwell’s Five-Minute Veterinary Consult  
Rhernia, etc. •  Contrast studies—both liquid 
barium and barium-coated food for radiolucent 
foreign bodies or esophageal strictures. Iohexol 
may also be used. Esophagram does not allow 
one to evaluate functional disorders such as 
intestinal dysmotility or cricopharyngeal 
muscle achalasia. Caution: contrast studies may 
increase the risk for aspiration pneumonia with 
regurgitation. •  Videofluoroscopy—for 
pharyngeal weakness, cricopharyngeal muscle 
dysfunction, esophageal motility disorders, 
hiatal hernia, or gastroesophageal reflux. 
• Other imaging studies include scintigraphy 
and high-resolution manometry for motility 
evaluation and ultrasound for pharyngeal or 
cervical masses. •  Cervical and thoracic CT 
scans may also be utilized.
• Esophagoscopy can be useful for esophagitis, 
strictures, vascular ring anomalies, neoplasia, 
and foreign bodies. •  Electromyography and 
nerve/muscle biopsies may be used for neuro -
pathic or myopathic conditions. •  T ranstracheal 
wash or bronchoalveolar lavage if aspiration 
pneumonia is present or suspected.
Gross and histologic findings depend upon 
the underlying etiology and the presence of 
complicating factors.
  TREATMENT
• Therapy for underlying etiology should be 
instituted. •  Important to meet nutritional 
requirements and treat or prevent aspiration 
• Aspiration pneumonia may require 
supplemental oxygen therapy, nebulization/
coupage, and fluid therapy with balanced 
electrolyte solution. •  These animals may be 
recumbent and require soft bedding. They 
should be maintained in sternal recumbency or 
turned to alternate down sides every 4 hours.
ACTIVITY
DIET
consistencies is essential. Liquid gruel, small 
meatballs, or blenderized slurries may be used. 
• Some cases benefit from gastrostomy 
feedings, though regurgitation may still occur. 
• Both food and water should be elevated, and 
animal should be maintained in an upright 
position for 10–15 minutes after eating or 
drinking. Use of a Bailey chair facilitates 
keeping the dog upright for 10–15 minutes 
after a meal. •  The recommend caloric 
requirement amount should be calculated and 
the diet should be monitored so that 
metabolizable energy requirements are met.CLIENT EDUCATION
• If regurgitation is due to megaesophagus, 
most cases require lifelong therapy, even if an 
underlying etiology is found. Client dedication 
is important for long-term management. 
• Most animals succumb to aspiration 
pneumonia or intractable regurgitation. 
• Placement of a percutaneous gastrostomy 
tube (PEG) tube in dogs with megaesophagus 
can reduce the frequency of aspiration 
pneumonia, leading to prolonged survival.
• Surgical intervention is indicated for 
vascular ring anomalies, cricopharyngeal 
muscle achalasia, bronchoesophageal fistula, 
and others. •  Esophageal dysfunction is 
permanent in most cases. •  Balloon dilation 
is indicated for cases of esophageal stricture.
(broad-spectrum or based on culture and 
sensitivity from transtracheal wash or 
bronchoalveolar lavage). •  Specific therapy for 
underlying etiology if indicated. •  Prokinetics—  
metoclopramide 0.2–0.4 mg/kg SC or PO 
q6–12h, or 1–2 mg/kg q24h as a CRI increases 
lower esophageal sphincter (LES) tone and 
increases gastric motility. Cisapride 0.5 mg/kg 
PO q8–12h is more effective for esophageal 
reflux than metoclopramide and has been 
documented to enhance gastric emptying and 
increase LES tone in dogs. •  Other motility 
agents (e.g., erythromycin) can enhance gastric 
emptying and possibly increase LES tone. •  H2 
receptor antagonists can be used for the short 
term to manage mild to moderate 
esophagitis—ranitidine 1–2 mg/kg PO, IV 
q12h, famotidine 0.5–1 mg/kg PO, SC, IM, 
IV q12h; however, are subject to tachyphylaxis 
(tolerance) when used for >4–5 days and are 
less potent compared to proton-pump 
inhibitors. Proton-pump inhibitors may be 
used in moderate to severe cases, and are also 
effective when administered for prolonged 
periods of time—omeprazole 0.7–1.5 mg/kg 
PO q12h. •  Sucralfate caplets or suspension 
can be administered to help reduce esophageal 
pain and promote healing of esophagitis and 
esophageal erosions or ulcerations.
N/A
may be compromised when coadministered 
with sucralfate. •  Injectable forms of acid 
suppressants should be used when applicable 
to avoid concerns with regurgitation of the 
drug before absorption.
N/A
  FOLLOW-UP
• Animals with aspiration pneumonia should 
have thoracic radiographs and complete blood 
counts checked until resolution, or if recurrence 
is suspected. •  Animals should be monitored, 
weighed, and body condition scores applied to 
ensure adequate caloric intake.
N/A
• Aspiration pneumonia. •  Others depending 
on presence of underlying diseases (e.g., 
hypothyroidism).
• Older animals with idiopathic megaesophagus 
have a poor prognosis. •  Aspiration pneumonia 
is the typical cause of death or euthanasia.
• Aspiration pneumonia. •  Megaesophagus.
Young animals may regain some esophageal 
function with appropriate therapy, depending 
on etiology.
None
N/A
SEE ALSO
• Dysautonomia (Key-Gaskell Syndrome). 
• Dysphagia. •  Esophagitis. 
• Megaesophagus. •  Myasthenia Gravis. 
• CK = creatine kinase. •  LES = lower 
esophageal sphincter. •  PEG = percutaneous 
endoscopic gastrostomy tube.
Guilford G, Strombeck D. Diseases of 
swallowing. In: Strombeck’s Small Animal 
Gastroenterology, 3rd ed. Philadelphia, PA: 
Saunders, 1996, pp. 211–235.
available onlineRegurgitation  (continued)

Canine and Feline, Seventh Edition  1187
R  BASICS
OVERVIEW
• Hyperchloremic metabolic acidosis due to 
decreased bicarbonate reabsorption in the 
proximal renal tubule (proximal or type 2 
renal tubular acidosis [RTA]) or decreased 
hydrogen ion secretion in the distal tubule 
(distal or type 1 RTA) in patients with normal 
or near normal glomerular filtration rate and 
absence of diarrhea.
• Aldosterone deficiency or resistance can 
cause type 4 distal RTA and hyperkalemia.
• Proximal RTA has not been documented as 
an isolated entity in dogs but has been 
observed as part of Fanconi syndrome.
• In distal RTA urine cannot be maximally 
acidified despite moderately to markedly 
decreased plasma bicarbonate concentration 
as a consequence of impaired hydrogen 
secretion in the collecting ducts. Urine pH 
typically is >6.0 (urine pH should be 4.5–5.0 
in the presence of systemic acidosis).
• Uncommon in both dogs and cats.
• Age range at time of diagnosis, 1–13 years.
SIGNS
• Acidemia may cause lethargy, muscle 
weakness (may be due to hypokalemia), 
inappetence, nausea, weight loss, stunted 
growth, and neurologic signs.
• Other signs depend on the associated 
diseases (e.g., pyelonephritis).
• Panting.
• Polyuria and polydipsia usually associated 
with hypokalemia or calciuresis.
• Hematuria and dysuria secondary to 
• Osteomalacia associated with chronic 
• May be primary (i.e., inherited), or 
secondary to hypercalciuria, toxins, drugs 
(e.g., amphotericin B), altered calcium 
metabolism causing nephrocalcinosis (e.g., 
hypervitaminosis D, primary hyperparathy -
roidism), autoimmune (e.g., immune-  
mediated hemolytic anemia, systemic lupus 
erythematosus [SLE], renal transplant 
rejection), hypergammaglobulinemic disorders 
(e.g., multiple myeloma, SLE), and tubuloint -
erstitial nephropathies.
• In cats, distal RTA has been associated with 
pyelonephritis, hepatic lipidosis, idiopathic 
with secondary hyperaldosteronism, and 
topical ophthalmic carbonic anhydrase 
inhibitor.• In dogs, clinical cases were idiopathic or 
associated with immune-mediated hemolytic 
anemia, leptospirosis, gastric-dilation-
volvulus, zonisamide therapy, or 
experimentally induced renal ischemia.
  DIAGNOSIS
Consider other causes of hyperchloremic 
normal anion gap metabolic acidosis (e.g., 
diarrhea, carbonic anhydrase inhibitors, 
ammonium chloride, cationic amino acids, 
post-hypocapnic metabolic acidosis, dilutional 
acidosis, hypoadrenocorticism). Small bowel 
diarrhea is the most important differential.
• Results vary depending on associated 
diseases.
• Hypokalemia due to increased renal excretion.
• Alkaluria (pH >6.0); rule out urease-
positive urinary tract infection.
Venous blood gas and serum electrolyte 
analysis indicates hyperchloremic normal 
anion gap metabolic acidosis. Urine pH is 
>6.0 in distal RTA vs. <5.5 in proximal RTA.
IMAGING
Radiography—may detect uroliths or 
osteomalacia.
• The key diagnostic feature is normal anion 
gap metabolic acidosis accompanied by an 
inappropriately alkaline urine pH (>6.0).
• Ammonium chloride tolerance test—
administer 200 mg/kg PO; measure urine pH 
before and hourly for 5 hours; empty the 
bladder hourly. Urine pH in normal dogs 
decreases to <5.5 within 4 hours. Avoid this 
test in severe acidemia.
• Type 1 and 2 RTA can be differentiated 
based on response to sodium bicarbonate 
infusion (0.5–1.0 mEq/kg/h). Fractional 
excretion of bicarbonate will increase 
markedly in type 2 RTA.
  TREATMENT
• Individualize depending on the nature and 
severity of associated conditions.
• Less bicarbonate is needed to resolve 
metabolic acidosis caused by distal RTA than 
is needed with proximal RTA.
• Hypokalemia may resolve with bicarbonate 
or citrate administration, but additional 
potassium supplementation may be required.  MEDICATIONS
• Acidosis—depending on the serum 
potassium concentration give potassium 
citrate alone ± sodium citrate; or sodium 
bicarbonate.
• Potassium supplementation—potassium 
gluconate if hypokalemia does not resolve 
with potassium citrate therapy alone.
Citrate should be avoided in patients 
receiving aluminum hydroxide; citrate can 
lead to excessive aluminum absorption.
  FOLLOW-UP
• Serial blood gas with electrolyte analyses 
(e.g., every 3–5 days) until acid–base status 
has normalized.
• Long-term prognosis depends on the nature 
and severity of associated conditions; may be 
reasonably good in patients without other 
diseases, little information exists on the long- 
term course of this disease.
SEE ALSO
Riordan L, Schaer M. Renal tubular acidosis. 
Comp Cont Ed Pract Vet 2005, 
27(7):513–529.
Consulting Editor  J.D. FosterRenal Tubular Acidosis

1188  Blackwell’s Five-Minute Veterinary Consult  
R  BASICS
OVERVIEW
One or both kidneys are abnormally large as 
detected by abdominal palpation or diagnostic 
imaging.
The kidneys may enlarge due to abnormal 
cellular infiltration (e.g., inflammation, 
infection, and neoplasia), urinary tract 
obstruction, acute tubular necrosis, or 
development of renal cysts or pseudocysts.
with decreased kidney function.
ulceration in uremia.
uremic blood loss or decreased red blood cell 
survival; impaired production of erythro- 
poietin.
• Hepatobiliary—may occur with porto -
systemic shunts.
• Nervous—depression and lethargy 
associated with uremia.
metabolic acidosis compensation.
• Polycystic kidney disease (PKD) occurs in 
several breeds of dogs and cats. Autosomal 
dominant inheritance in bull terriers and 
Persian cats; autosomal recessive in Cairn and 
West Highland white terriers.
SIGNS
• May be asymptomatic, especially if only 
one kidney is affected.
• Loss of appetite.
• Discolored urine.
• Abdominal enlargement.
• Rarely lameness because of hypertrophic 
osteopathy associated with renal neoplasia.
• Abdominal mass or pain.
• One or both kidneys palpably large.
• Asymmetric kidneys.
• Pallor.
• Uremic halitosis.CAUSES & RISK FACTORS
Developmental/Acquired Disorders
• Hydronephrosis—unilateral or bilateral 
renomegaly secondary to ureteral obstruction 
or ectopic ureters.
• PKD—bilateral renomegaly in cats leading 
to chronic kidney disease (CKD).
• Hematoma—secondary to trauma.
• Compensatory hypertrophy—unilateral 
renomegaly secondary to disease of the other 
kidney.
• Perinephric pseudocyst—unilateral or 
bilateral enlargement. Kidney size may be 
normal, but subcapsular fluid accumulation 
enlarges capsule margins.
Metabolic
• Portosystemic shunt, acromegaly.
• Males have larger kidneys than females.
• Lymphoma—most often occurs in cats and 
causes bilateral renomegaly; rarely unilateral.
• Renal carcinoma—most common renal 
tumor of dogs; often causes unilateral 
• Nephroblastoma—congenital renal tumor, 
may not be diagnosed until the patient is 
older; usually unilateral.
• Sarcoma—usually cause unilateral 
• Cystadenocarcinoma—bilateral renal tumor 
in German shepherd dogs; often associated 
with skin lesions.
• Feline leukemia virus (FeLV) infection 
predisposes cats to renal lymphoma.
• Renal abscess.
Toxic
• Ethylene glycol—bilateral renomegaly 
secondary to renal tubular swelling and 
infiltration by calcium oxalate crystals.
• See Acute Kidney Injury.
  DIAGNOSIS
• Distinguish from other abdominal masses.
• Confirmation may require diagnostic 
imaging or exploratory celiotomy.
• Azotemia, hyperphosphatemia, and 
inadequate urine concentration.
• Leukocytosis—infectious, inflammatory, 
and neoplastic causes.
• Nonregenerative anemia—CKD or 
inflammatory disorder.• Hyperglobulinemia—infectious or 
inflammatory disorder.
• Hematuria and proteinuria—renal neoplasia.
• Polycythemia and leukocytosis rarely 
accompany some renal neoplasms.
• Neoplastic cells rarely observed in urine 
with renal neoplasia.
• Test for FeLV infection if renal lymphoma 
is suspected.
• Serum protein electrophoresis distinguishes 
polyclonal from monoclonal hyperglobulinemia.
• Test for leptospirosis if indicated.
IMAGING
• Abdominal radiographs to confirm 
renomegaly and identify causes of ureteral 
• Renomegaly on the ventrodorsal view: 
>3 or 3.5 times the length of the L2 vertebra 
in cats or dogs, respectively.
• Excretory urography or CT to confirm 
renomegaly, hydronephrosis, and space-
occupying masses.
• Antegrade pyelography may exclude 
ureteral obstruction.
• Thoracic radiography indicated to detect 
• Distinguish between PKD, perinephric 
pseudocysts, hydronephrosis, neoplasia, 
abscess, and subcapsular hematoma.
• Acute inflammation may be associated with 
increased cortical echogenicity, perinephric 
effusion, or a medullary band of increased 
echogenicity.
aspirate can confirm renal cyst, abscess, or 
neoplasia. Due to potential for seeding of 
neoplastic cells in the abdominal wall, 
fine-needle aspiration should be avoided if 
some renal tumors (e.g., renal carcinoma) are 
• If renal aspirate is nondiagnostic, biopsy 
  TREATMENT
• Diagnose and treat underlying cause of 
• Outpatient unless dehydration or 
decompensated renal failure exist.
• Therapeutic renal diet is indicated to 
prolong survival time for CKD when serum 
creatinine exceeds 2 mg/dL.
• Administer balanced electrolyte solution 
intravenously or subcutaneously to maintain 
hydration as needed.Renomegaly

Canine and Feline, Seventh Edition  1189
R• If the patient has dehydration or continuing 
fluid losses such as vomiting or diarrhea, 
administer fluids intravenously to correct 
hydration deficits, maintain daily fluid need, 
and replace ongoing losses.
Vary with the cause.
Avoid nephrotoxic drugs.
  FOLLOW-UP
• Perform physical examination and weigh 
patient to assess hydration.• CBC, serum chemistries, urinalysis, 
blood pressure measurements are 
indicated depending on the underlying 
cause.
CKD, depending on underlying cause of 
Leptospirosis can be spread by contact with 
infected urine.
SEE ALSO
• Perirenal Pseudocysts.• Polycystic Kidney Disease.
• PKD = polycystic kidney disease.
Cuypers MD, Grooters AM, Williams J, 
et al. Renomegaly in dogs and cats. Part I: 
Differential diagnosis. Compend Contin 
Educ Pract Vet 1997, 19:1019–1033.
Allyson C. Berent.(continued)  Renomegaly

R1190  Blackwell’s Five-Minute Veterinary Consult  
RRespiratory Parasites
  BASICS
Helminths, arthropods, and protozoa that 
reside in the respiratory tract or pulmonary 
vessels of dogs and cats.
Infestation with parasites causes rhinitis, 
bronchitis, pneumonitis, or arteritis, 
depending on the location of the organism 
within the respiratory system. Eosinophilic 
inflammation usually results from invasion of 
the parasite.
• Respiratory. • Cardiovascular. • Hepatic—
with hepatopulmonary migration of some 
parasites ( Toxocara  spp.). • Neurologic—with 
migration of parasites to the brain ( Cuterebra ) 
or cerebral hemorrhage ( Angiostrongylus ).
GENETICS
There is no genetic basis.
Depends on parasite.
• Pneumonyssoides caninum , Aelurostrongylus 
abstrusus , Linguatula serrata , Oslerus 
(Filaroides) osleri , Crenosoma vulpis , Eucoleus 
(Capillaria) aerophilus , Toxoplasma gondii , 
Toxocara  spp.—worldwide. • Eucoleus boehmi , 
Cuterebra  spp., Filaroides hirthi , Paragonimus 
kellicotti —primarily North America. 
• Andersonstrongylus (Filaroides) milksi —
North America, Europe. • Angiostrongylus 
vasorum —various countries of Europe, Africa, 
South America, North America.
Species
SIGNS
• Four basic categories—upper airway (nasal 
cavity and sinuses), lower respiratory (trachea 
and bronchi), pulmonary parenchyma, and 
vascular; based on location and lifestyle of 
parasite. • Often insidious and chronic, with 
few clinical signs. • Respiratory compromise 
often not severe.
• Upper respiratory—sneezing; nasal 
discharge (serous, sanguinous); reverse 
sneezing; nasal irritation or rubbing; 
neurologic signs with Cuterebra  spp. • Lower 
respiratory and parenchyma—may have no 
clinical signs, variable coughing, tachypnea, 
or altered respiratory pattern. • Vascular—
can have weight loss, lethargy, coughing, 
exercise intolerance. Acute onset of 
respiratory distress if embolization or 
hemorrhage occurs.Physical Examination Findings
• Upper respiratory—similar to historical 
findings; variable. • Lower respiratory and 
parenchyma—cough elicited on tracheal 
palpation; occasionally harsh lung sounds.  
• Vascular—may present with signs of 
pulmonary disease, right-sided heart failure, 
anemia, coagulopathy, neurologic signs.
CAUSES
• Upper respiratory (nasal cavity and 
sinuses)— Pneumonyssoides caninum , Eucoleus 
boehmi , Linguatula serrata , Cuterebra  spp.  
• Lower airway (trachea and bronchi)—dogs 
and cats: Eucoleus (Capillaria) aerophilus  (rare 
in cats); dogs: Oslerus osleri , Filaroides hirthi , 
Andersonstrongylus milksi , Crenosoma vulpis . 
Cuterebra  spp. in the trachea. • Pulmonary 
parenchyma—dogs and cats: Paragonimus 
kellicotti , Toxoplasma gondii ; dogs: Filaroides 
hirthi , Andersonstrongylus milksi ; cats: 
Aelurostrongylus abstrusus , Troglostrongylus 
brevior , Troglostrongylus subcrenatus .  
• Vascular—dogs and cats: Dirofilaria 
immitis , larval migration of Toxocara canis  and 
T. cati ; dogs: Angiostrongylus vasorum .
• Depends on the specific parasite—some 
have intermediate or paratenic hosts that must 
be ingested by the definitive host, putting 
hunting or scavenging animals at higher risk. 
• Crenosoma vulpis —snails. • Paragonimus 
kellicotti —snails, crabs, shellfish. 
• Aelurostrongylus abstrusus —snails and slugs; 
transport hosts: rodents, frogs, lizards, birds. 
• Linguatula serrata —ingestion of sheep offal. 
• Toxoplasma gondii —ingestion of infected 
small mammals and birds or less commonly 
by ingesting sporulated oocysts in soil or 
water. • Multi-animal households with 
unhygienic living conditions—allows fecal–  
oral or direct-contact transmission. 
• Angiostrongylus vasorum —gastropods (slugs/
snails) or frogs are the intermediate host. Frogs 
can also serve as paratenic hosts.
  DIAGNOSIS
• Upper respiratory—other causes of epistaxis, 
rhinitis, or sinusitis (see specific chapters). 
• Lower respiratory—acute bronchitis 
(nonparasitic); chronic bronchitis; infectious 
tracheobronchitis. • Pulmonary parenchyma—
eosinophilic lung disease; bronchopneumonia; 
granulomatous pneumonia; pulmonary 
granulomatosis. • Vascular—other causes of 
coagulopathy, right-sided heart failure, or 
pulmonary artery disease.
• CBC—variable; may note eosinophilia, 
basophilia, neutrophilia, and monocytosis; 
can see anemia with Angiostrongylus vasorum . • Biochemistry—often normal; high liver 
enzyme activity with some parasites during 
early stages as a result of hepatic migration if 
burden is substantial. • Urinalysis—normal.
Coagulopathy with Angiostrongylus vasorum  
or severe cases of heartworm disease 
(disseminated intravascular coagulation).
IMAGING
• Often nonspecific findings—generalized 
interstitial pattern; peribronchiolar infiltrates, 
nodular to alveolar pattern. • Oslerus —soft 
tissue nodular densities within the trachea at 
the level of the carina. • Paragonimus —can 
see bullae, cystic lesions or pneumothorax due 
to bulla or cyst rupture. • Dirofilaria —right-
sided heart enlargement, tortuous and 
truncated pulmonary arteries, pulmonary 
infiltrates (dogs). Few cardiac changes in cats, 
large pulmonary arteries possible.
Sputum Examination
May reveal eggs or larvae (L-1).
Fecal Examination
• Multiple examinations often necessary; 
negative results do not rule out infection.  
• Direct fecal smear: Angiostrongylus  (larvae). 
• Standard fecal flotation: Eucoleus aerophilus  
(eggs), Eucoleus boehmi  (eggs). • Zinc sulfate 
centrifugation: Aelurostrongylus  (larvae) , Oslerus 
osleri, Andersonstrongylus milksi , Filaroides hirthi  
(larvae, larvated eggs), Angiostrongylus vasorum  
(larvae). • Baermann: Aelurostrongylus  (larvae), 
Oslerus osleri , Andersonstrongylus milksi , 
Filaroides hirthi  (larvae, eggs), Crenosoma  
(larvae, larvated eggs), Angiostrongylus  (larvae). 
• Sedimentation: Paragonimus  (eggs).
• Upper respiratory—examination via 
retrograde pharyngoscopy or rhinoscopy with 
antegrade flushing of anesthetic gas can allow 
visualization of nasal mites; retrograde nasal 
lavage and cytologic examination of fluid can 
be helpful. • Eucoleus boehmi— histopathology 
can reveal eggs deep within the epithelium. 
• Linguatula serrata— diagnosis made by 
observation of eggs in nasal secretions or 
around the nares.
• Lower respiratory and parenchyma—rarely 
can see tracheal and bronchial parasites and 
parasitic nodules; occasionally can be removed 
for definitive identification. • T racheal wash or 
bronchoalveolar lavage can allow identification 
of larvae ( Oslerus osleri , Aelurostrongylus , 
Crenosoma , Filaroides hirthi , Andersonstrongylus 
milksi , Angiostrongylus ); eggs ( Eucoleus 
aerophilus, Paragonimus ); organisms ( Toxoplasma ). 
• Oslerus osleri —can also be diagnosed by 
brushings or histopathology of nodules at 
the carina.

Canine and Feline, Seventh Edition  1191
RRPATHOLOGIC FINDINGS
• Upper respiratory—may find nasal mites or 
worms in epithelium of sinuses and nasal 
cavity. • Lower respiratory and parenchyma—
can see pulmonary nodules containing 
parasites throughout the parenchyma or 
within bronchi. • Vascular—changes include 
thrombi and intimal proliferation of the 
vascular walls. • Cuterebra  spp. can be found 
in brain sections when associated with 
  TREATMENT
Most commonly outpatient—upper and 
lower respiratory parasites; may need repeated 
examinations to monitor response.
Supportive care and oxygen therapy can be 
needed depending on the severity of disease.
ACTIVITY
Strict cage rest if severe pulmonary 
dysfunction occurs with upper or lower 
respiratory parasites; also with vascular 
parasite infection or bullous lung disease 
associated with Paragonimus .
 DIET
No special restrictions.
• Explain that treatment duration and response 
depend on the type of parasite. • Warn client 
of the risk of recurrence in animals that 
maintain lifestyles conducive to transmission of 
the parasites (e.g., hunting, sporting dogs, 
multidog households, outdoor cats).
Ruptured Paragonimus  cysts generally require 
• Anthelmintics—few studies confirm 
efficacy; most data anecdotal. For treatment 
of Dirofilaria , see chapters on Heartworm 
Disease. • Pneumonyssoides caninum —
selamectin 6–24 mg/kg applied every 2 weeks 
for three treatments. milbemycin oxime 
0.5–1 mg/kg PO weekly for 3 weeks, 
ivermectin 200 μg/kg SC or PO for two 
treatments 3 weeks apart; note: not labeled for 
use in dogs at this dosage. • Cuterebra —
ivermectin 300 μg/kg SC or PO every other 
day for three doses combined with a tapering 
dose of corticosteroids. • Linguatula serrata —
physical removal of organisms from the 
sinuses. • Eucoleus aerophilus , E, boehmi —
ivermectin 200 μg/kg PO once; fenbendazole 25–50 mg/kg q12h for 10–14 days; very 
difficult to clear. • Oslerus osleri —efficacious 
therapy not fully determined. Consider 
ivermectin 400 μg/kg SC or PO q3 weeks for 
four doses. • Crenosoma vulpis —levamisole 
7.5 mg/kg SC q48h (two doses); 
fenbendazole 50 mg/kg PO q24h for 7 days; 
milbemycin oxime 0.5 mg/kg PO once. 
• Aelurostrongylus abstrusus —fenbendazole 
25–50 mg/kg PO q24h for 10 days; 
ivermectin 400 μg/kg SC, selamectin spot-on 
formula 45 mg/cat, two doses, 23 days apart. 
• Filaroides hirthi , Andersonstrongylus 
milksi— fenbendazole 50 mg/kg PO q24h for 
14 days; albendazole 50 mg/kg PO q12h for 
5 days, repeat in 3 weeks. • Paragonimus 
kellicotti— praziquantel 25 mg/kg PO, SC 
q8h for 3 days; fenbendazole 25–50 mg/kg 
PO q12h for 14 days. • Toxoplasma —
clindamycin 12.5 mg/kg PO q12h for 28 
days. • Angiostrongylus vasorum —
fenbendazole 20–50 mg/kg PO q24h for 
5–21 days; milbemycin oxime 0.5 mg/kg PO 
weekly for 4 weeks; single topical application 
of moxidectin 2.5 mL/kg. • Toxocara  spp. 
larval migration—fenbendazole 50 mg/kg PO 
q24h for 10 days. • Anti-inflammatory agents—  
recommendations for concurrent use of 
steroids vary.
Ivermectin—not labeled for use in dogs or 
cats other than for heartworm prophylaxis; 
contraindicated at dosages >100  μg/kg in 
breeds with known sensitivity (collies, collie 
breeds, and Australian shepherd dogs).
None
None
  FOLLOW-UP
• Serial fecal Baermann larval extractions or 
examination for eggs—some anthelmintics can 
suppress egg or larval production in some 
species and intermittent shedding reduces 
value of repeated fecal exams. • Resolution of 
clinical signs—suggests response to treatment; 
does not indicate complete clearance of 
parasites. • Peripheral eosinophilia, if noted 
initially, may subside with treatment. • Repeat 
bronchoscopic examination—can help assess 
efficacy of treatment for Oslerus osleri .
• Avoid activity that predisposes to 
infestations (often not practical). • Avoid 
contact with wildlife reservoirs (especially 
wild canids and felids). • Consider 
prophylactic treatment for heartworm.POSSIBLE COMPLICATIONS
• Chronic pulmonary damage—possible with 
persistent and heavy lower respiratory parasite 
burdens. • Infestations generally not fatal; 
however, severe pulmonary damage can result 
with some species; Cuterebra  spp. and 
Angiostrongylus  can cause fatal neurologic 
complications. • Pneumonyssoides caninum  has 
been associated with gastric dilation and volvulus.
usually fair to excellent; variable. • Return to 
performance—depends on chronicity of 
disease and level of chronic pulmonary 
damage by lower respiratory parasites. 
• Recurrence possible.
ZONOTIC POTENTIAL
None
SYNONYMS
• Lungworm infestation— Aelurostrongylus , 
Eucoleus (Capillaria) aerophilus , Crenosoma , 
Oslerus osleri , Filaroides hirthi , Andersonstrongylus 
milksi . • Nasal mite infestation— Pneumonys-
soides caninum , Pneumonyssus caninum . 
• French heartworm— Angiostrongylus vasorum .
SEE ALSO
Bowman DD. Respiratory system parasites of 
the dog and cat, Part I: Nasal mucosa and 
sinuses, and respiratory parenchyma and Part 
II: T rachea and bronchi, and pulmonary 
vessels: http://www.ivis.org/advances/
Parasit_Bowman/ddb_resp/ivis.pdf
Lacorcia L, Gaser R, Anderson BA, Beveridge 
I. Comparison of bronchoalveolar lavage 
fluid examination and other diagnostic 
techniques with the Baermann technique 
for detection of naturally occurring 
Aelurostrongylus abstrusus  infection in cats. 
J Am Vet Med Assoc 2009, 235(1):43–49.
Marks SL, Moore MP , Rishniw M. 
Pneumonyssus caninum:  the canine nasal 
mite. Compend Contin Educ Pract Vet 
1994, 16:577–582.
acknowledges the prior contribution of Jill S. 
Pomrantz.
available online(continued)  Respiratory Parasites

1192  Blackwell’s Five-Minute Veterinary Consult  
RRetained Placenta
  BASICS
OVERVIEW
• Dogs—placenta retained beyond the 
immediate postpartum period; placentas 
usually passed within 15 minutes of birth of a 
puppy; may develop acute metritis secondary 
to retained placenta.
• Cats—may retain placentas for days 
without signs of illness.
• Extremely uncommon.
• Dog—rare, most common in toy dog 
breeds.
SIGNS
• Recent parturition.
• Continued vulvar discharge of lochia.
• Owner may note number of placentas 
passed, although this information is 
frequently unreliable.
• Green lochia vulvar discharge.
• Palpation of firm mass in uterus—not 
always possible.
• Concurrent clinical signs of postpartum 
metritis.
• Toy breed.
  DIAGNOSIS
• Postpartum metritis—physical examination 
and vaginal cytologic examination show no 
signs of infection with uncomplicated 
retained placenta; metritis may develop 
• Retained fetus—differentiated by 
radiography or ultrasonography.
Usually normal when uncomplicated.
Vaginal cytologic examination—parabasal 
epithelial cells; may note erythrocytes; 
biliverdin clumps.IMAGING
Ultrasonography—echogenic but nonfetal 
mass within the uterus.
Celiotomy or hysterotomy—may be required 
  TREATMENT
• Outpatient for healthy bitch or queen.
• Instruct owner to monitor rectal 
temperature and observe for signs of systemic 
illness.
• Ovariohysterectomy—curative; recom-
mended if future breeding is not a 
consideration.
• Surgical removal—indicated if medical 
treatment is unsuccessful and the bitch 
develops metritis.
• Oxytocin—known or suspected condition 
in otherwise healthy cats and dogs; dogs: 
0.5 IU/kg IM, up to 5 IU total dose; cats: 
0.5–1 IU IM. Oxytocin may be ineffective 
after 48 hours postpartum.
• Can precede oxytocin treatment with 
calcium gluconate (10%); dogs and cats, 
0.5–1.5 mL/kg IV slowly over 15 minutes; 
monitor for bradycardia during injection.
• Metritis—treat accordingly (see Metritis).
Do not give progestational drugs.
  FOLLOW-UP
• Monitor temperature and physical 
• Acute metritis (dogs)—may develop if the 
placenta is not passed; fair to good prognosis 
for recovery with treatment.
• Prognosis for future reproduction—good 
without metritis; fair to poor with metritis.  MISCELLANEOUS
SEE ALSO
Metritis
Feldman EC, Nelson RW. Periparturient 
diseases. In: Feldman EC, Nelson RW, eds., 
Saunders, 2004, pp. 808–834.
Grundy SG, Davidson AP . Theriogenology 
question of the month. Acute metritis 
secondary to retained fetal membranes and 
a retained nonviable fetus. J Am Vet Med 
Assoc 2004, 224(6):844–847.

Canine and Feline, Seventh Edition  1193
RRetinal Degeneration
  BASICS
• Degeneration of the retina from inherited or 
acquired causes. • Inherited—generalized 
progressive retinal atrophy (PRA); a group of 
progressive retinal diseases; may be subdivided 
into photoreceptor dysplasias (begin before retina 
fully develops <8 weeks) and photoreceptor 
degenerations (begin after retina matures).
• A number of genetic defects in photoreceptor 
metabolism have been identified. • May be 
secondary to retinal pigment epithelial or 
choroidal disease; amino acid metabolic 
disorders, and storage diseases. • Central 
PRA: genetic defect in vitamin E metabolism, 
or acquired with vitamin E deficiency. • May be 
idiopathic, secondary to diffuse or focal 
inflammation and scarring (e.g., chorio­
retinitis), toxin exposure, nutritional 
deficiency, or previous retinal detachment. 
syndrome (SARDS): idiopathic, may be 
immune ­mediated retinitis.
GENETICS
Dogs
• PRA—generally autosomal recessive, 
dominant in mastiffs. • Neuronal ceroid 
lipofuscinosis—generally autosomal recessive. 
• Hemeralopia—cone degeneration, auto­
somal recessive. • Inheritance in many breeds 
not determined.
Cats
• Early onset—mixed breed and Abyssinian 
retinal dysplasia (rod ­cone dysplasia), autosomal 
dominant. Persians, autosomal recessive. • Late 
onset—Abyssinian rod ­cone degeneration, 
autosomal recessive. • Late onset—PRA in 
many breeds, including Siamese.
• Hereditary—prevalence greater in dogs 
than cats. • Taurine deficiency—uncommon 
with nutritionally complete cat foods.
Central PRA—more common in dogs from 
Europe than United States.
Species
Hereditary—Dogs • Retinal dysplasia—
Bedlington terrier, Sealyham terrier, English 
springer spaniel, cocker spaniel, others. 
• Early­onset PRA—Irish setter, collie, Norwegian 
elkhound, miniature schnauzer, Belgian 
shepherd dog, mastiff, Cardigan Welsh corgi, American Staffordshire terrier, pit bull terrier, 
briard (congenital stationary night blindness). 
• Late­onset PRA—miniature and toy 
poodle, American and English cocker spaniel, 
basenji, Labrador retriever, Tibetan terrier, 
dachshund, Akita, Samoyed, Siberian husky. 
• Central PRA—Labrador, golden retriever, 
border collie, collie, Shetland sheepdog, 
briard, others. • Cone degeneration disease—
German shorthaired pointer, Alaskan 
Malamute, and Australian shepherd dog. 
• Neuronal ceroid lipofuscinosis—English 
setter, border collie, American bulldog, 
Dalmatian, Tibetan terrier, collie. 
• SARDS—Brittany spaniel, miniature 
schnauzer, dachshund, others.
Hereditary—Cats
• Abyssinian, Somali, Persian. • Siamese 
breed group—autosomal recessive (CEP290).
• Early PRA and dystrophies—3 months–2 years. 
• Late PRA—clinical signs >4–6 years. 
• Cone degeneration disease—3–4 months. 
• SARDS—middle ­aged to old.
• PRA—X ­linked recessive condition in Siberian 
husky and Samoyed, therefore primarily males. 
• SARDS—70% female.
SIGNS
• PRA (dog)— gradually progressing 
nyctalopia that ultimately affects vision in 
bright light; may note dilated pupils or 
brighttapetal reflex; may appear acutely blind. 
Dysplasias have early onset and blindness by 
2 years. Degenerations are later onset and 
blind in later life. • Hemeralopia or cone 
degeneration disease—rare. Between 8 and 12 
weeks of age puppies show photophobia and 
trouble navigating in bright light. Progresses 
to total day blindness. Night vision remains 
normal. • Central PRA (dogs)—rare in 
United States; central vision lost; may never 
become completely blind. • SARDS—vision 
lost in 1–4 weeks; polyuria, polydipsia, and 
polyphagia common.
• If severe—direct and consensual pupillary 
light reflexes impaired or nearly abolished. 
• Tapetal hyperreflectivity and nontapetal 
depigmentation or mottled hyperpig­
mentation; retinal blood vessel attenuation 
and optic nerve atrophy. • PRA (dogs)—
cataracts and vitreous degeneration can occur. 
• SARDS (dogs)—obesity; may note slow 
or absent pupillary light reflexes (PLR). 
Chromatic PLR testing (melan 100), reduced 
or no red PLR, normal blue PLR. • Borzoi 
chorioretinopathy—multifocal chorioretinal 
lesions (hyperpigmented and hyperreflective). 
• Taurine ­deficient retinopathy (cats)—
begins as a spot in area centralis; then 
horizontal band forms superior to optic nerve; finally, diffuse degeneration and 
hyperreflectivity. • Storage diseases—may 
have cloudy corneas and possibly neurologic 
signs. • Neuronal ceroid lipofuscinosis—
mental deterioration, paralysis, and death.
CAUSES
• PRA—affects both eyes symmetrically. 
• Chronic or uncontrolled glaucoma—retinal 
and optic nerve atrophy. • Secondary to 
scarring from previous multifocal or diffuse 
retinal detachment or inflammation.
Anomalous
• Rod­cone dysplasias—affect both eyes. 
• Other dysplasias—may be multifocal and 
nonblinding (e.g., English springer spaniel, 
Labrador retriever). • Oculoskeletal dysplasia 
in Labrador and Samoyed.
Metabolic
• Storage disease—mucopolysaccharidosis, 
gangliosidosis, mannosidosis, fucosidisis 
(English springer spaniel). • Ornithine 
aminotransferase deficiency—progressive and 
total atrophy of choroid and retina; older cats.
Neoplastic infiltrate may lead to scars from 
previous retinal detachment if treated.
• Severe deficiency of vitamin E or A (dogs 
and cats)—may cause partial or complete 
degeneration. • Taurine deficiency (cats)— 
retinal degeneration, dilated cardiomyopathy.
Infectious/Immune
• Retina will degenerate from inflammation; may 
be focal, multifocal, or generalized. SARDS—
some cases are immune ­mediated retinitis.
SARDS—dogs; post ­inflammatory—dogs 
and cats.
Toxic
• Idiosyncratic reaction to griseofulvin or 
enrofloxacin (cats). • Radiation—dogs or cats 
treated for nasal or CNS neoplasia. 
• Phototoxicity—operating microscopes, 
welding light exposure.
• Ocular disease—cataracts, panuveitis, 
chorioretinitis, retinal detachment, glaucoma. 
• Cats—enrofloxacin dose should not exceed 
5 mg/kg/day. Toxicity noted at lower doses in 
compromised animals (i.e., renal disease).
  DIAGNOSIS
• Acute vision loss, PLR slow or absent—
SARDS, optic neuritis, retinal detachment, 
unrecognized PRA, or glaucoma; PLR 
normal—rapidly developing diabetic cataracts

1194  Blackwell’s Five-Minute Veterinary Consult  
Ror visual cortex disease. • Slowly progressive 
visual loss—PRA, cataracts, severe corneal 
disease (e.g., pigmentation, scarring, or 
edema), chronic retinitis, chorioretinitis, 
vitreal inflammation.
• Usually normal, unless systemic disease. 
• SARDS (dogs)—may suggest hyperadreno ­ 
 corticism.
• Test for hyperadreoncorticism, evaluate sex 
hormone levels, check blood pressure, 
evaluate for proteinuria with SARDS. 
• Taurine concentration (cats)—especially 
with dilated cardiomyopathy. • Serum and 
urine ornithine concentrations (cats)—
elevated with ornithine aminotransferase 
deficiency. • Genetic testing ­ many tests are 
available from many different companies; 
VetGen, Animal Genetics, Animal Labs, 
Embark Vet are examples. May identify 
affected, non ­affected and carriers.
IMAGING
• Thoracic radiographs and cardiac 
ultrasound—in cats with suspected taurine 
deficiency. • CT or MRI—investigate causes 
of central blindness.
• Ophthalmic examination. 
• Electroretinography—localizes cause of 
blindness when retina not visible or appears 
normal. • Chromatic PLR (Melan 100)—
differentiates outer retinal layer problems (red 
reduced) vs. inner retina layers (absent blue). 
Definitive diagnosis requires electroretinogram 
as interpretation can be confounded by iris 
atrophy and stress ­induced mydriasis. 
• Cerebrospinal fluid tap—for cases of 
suspected optic neuritis.
• Thin retina. • Edges of focal retinal scars—
sharply delineated. • Hyperpigmented areas—  
associated with postinflammatory scars or 
central PRA. • End­stage degenerations—
marked photoreceptor atrophy and reduction 
in retinal cell density. • Lipopigment 
accumulated in neuroepithelium—central 
PRA, ceroid lipofuscinosis, congenital 
stationary night blindness. • Lysosome storage 
diseases—accumulation in neuronal/retinal 
layers/cornea.
  TREATMENT
DIET
• Cats—food should contain 500–750 ppm 
taurine. • Dogs—balanced diet, avoid those 
high in polyunsaturated fats.CLIENT EDUCATION
• Most blind animals function well in 
stable environment. • Blind dogs should 
be supervised if outside, in unfenced yards 
or in an area with a pool. • Suggest playing 
with toys that make sounds. • Older blind 
animals with hearing loss or senility may 
not adapt well. • Some blind animals 
experience behavioral changes such as 
aggression or reduced activity. • Animals 
with only one blind eye can function 
normally. • Blind cats should be kept 
indoors.
Not indicated unless painful.
• None currently effective. • Pyridoxine—
for ornithine aminotransferase deficiency 
(cats). • Adequate dietary taurine—halt 
progression of taurine ­deficient retinopathy. 
• SARDS—if autoimmune retinitis, 
immune suppressive treatment may preserve/  
restore some vision.
GENE THERAPY
Experimental—retinal pigment epithelium 
dystrophy in briard.
N/A
Cataract surgery—not recommended if 
retinal degeneration is severe; perform 
preoperative electroretinogram.
  FOLLOW-UP
• Serial fundic examinations—signs of 
degeneration over weeks with SARDS; 
months with PRA. • Cataract formation—
with PRA or SARDS.
• Do not breed known or suspected carriers 
of PRA or other heritable diseases. • Genetic 
testing on breeding animals.
• Cataracts. • Glaucoma. • Uveitis. • Ocular 
trauma (result of visual impairment). 
• Obesity (reduced activity).
PROGNOSIS
• Inherited PRA—progresses to blindness; 
slow progression allows patient to adapt to visual loss. • Degeneration from inflamm­
ation—usually does not progress unless 
persistent or recurrent inflammation. 
• SARDS—irreversible blindness. • Taurine 
deficiency (cats)—degeneration may halt at 
any stage.
SARDS—hyperadrenocorticism, proteinuria, 
hypertension, elevated sex hormones.
N/A
N/A
N/A
SYNONYMS
• PRA—progressive rod ­cone degeneration; 
retinal atrophy. • Taurine ­deficient 
retinopathy—feline central retinal 
SEE ALSO
• Blind Quiet Eye.
• Chorioretinitis.
• Lysosomal Storage Diseases.
• PLR = pupillary light reflex. 
• PRA = progressive retinal atrophy. 
Narfström K, Petersen ­Jones S. Diseases of 
the canine ocular fundus. In: Veterinary 
Blackwell, 2013, pp. 2087–2235.
available onlineRetinal Degeneration  (continued)

Canine and Feline, Seventh Edition  1195
RRetinal Detachment
  BASICS
Separation of the neural retina from the 
retinal pigment epithelium (RPE).
• Subretinal space—a potential space between 
RPE and neural retina in which fluid or 
exudates accumulate. • Etiopathogenesis is 
one or a combination of rhegmatogenous 
(retinal tear), subretinal exudation, or 
traction.
Rhegmatogenous Retinal Detachment 
(RRD)
A tear or hole in retina related to age, 
cataracts, traction from inflammatory debris 
or vitreal degeneration, trauma, or retinal 
degeneration. Vitreous fluid moves into the 
subretinal space, resulting in detachment. 
Probably the predominant type occurring in 
association with cataracts and after cataract or 
lens surgery.
Exudative
• Fluid accumulates in the subretinal space 
because of breakdown of blood–retinal 
barrier. • Subretinal fluid—serous, hemor-
rhagic, or exudative. • Hematogenous/
systemic pathogenetic factors—common. 
• Vasculitis, hypertension, and hyperviscosity—
may cause serous detachment with or without 
Traction
• Fibrous or fibrovascular tissue; detaches 
retina and/or may cause retinal tear. 
• Associated with trauma, intraocular foreign 
bodies, or any cause of severe vitreal 
• Nervous. • Ophthalmic. • May be 
manifestation of systemic disease or neoplasia.
GENETICS
Depends on cause—dogs with hereditary 
cataracts or lens luxation may develop RRD. 
Some breeds may develop RRD from primary 
vitreous abnormalities (shih tzu), colobomas 
of optic nerve (collie), or severe retinal 
dysplasia inducing retinal tears or traction.
• Exudative—most common in dogs and 
cats. • RRD—uncommon. More common in 
dogs because of the greater prevalence of 
severe vitreal degeneration, cataracts, and 
cataract surgery.
Varies with the distribution of infectious 
etiologies.
Species
• Depends on cause. • Terrier breeds—
predisposed to primary lens luxation, may 
contribute to RRD. • Breeds that develop 
cataracts. • Shih-tzu, Boston terrier, Italian 
greyhound, Chihuahua, corgi—predisposed 
to spontaneous RRD owing to abnormal 
liquefied vitreous. • Dogs with merle coat 
color (Australian shepherd dog, Shetland 
sheepdog, Great Dane, collie) may have 
severe retinal dysplasia and optic nerve or 
scleral colobomas, leading to RRD. • Breeds 
with severe retinal dysplasia: English springer 
spaniel, Labrador retriever, Bedlington terrier. 
• Breeds with serous retinopathy (also known 
as RPE dysplasia, canine multifocal 
retinopathy): Great Pyrenees, mastiff, coton 
de T ulear.
• Depends on cause. • Older patients—
cataracts and systemic diseases (e.g., hyper  - 
tension, neoplasia, immune-mediated disease). 
• Young dogs—retinal dysplasia, canine 
multifocal retinopathy, uveodermatologic 
syndrome.
SIGNS
• Blindness or reduced vision in affected eye. 
• Dilated pupil with slow or no pupillary 
light response (PLR). PLR may be near 
normal if detachment is acute. • Blood vessels 
or a “membrane” may be observed easily 
through the pupil just behind the lens. 
• Vitreous abnormalities—floaters, 
hemorrhage, or syneresis (liquefaction); 
common. • Interruption or alteration of 
course of blood vessels due to retinal 
elevation. • With clear subretinal fluid—
vessels may cast shadows. • With exudative 
fluid or blood, tapetum/RPE may not be 
visible. • Other signs related to underlying 
systemic disease or inflammation (see 
Chorioretinitis). • Canine multifocal 
retinopathy—multifocal gray to tan elevated 
lesions (focal detachments) of various size. 
Starts around 11 weeks, progresses with time.
CAUSES
Bilateral—suggests a systemic problem, 
except in breeds with a predisposition to 
severe vitreal degeneration (e.g., shih tzu).
End-stage progressive retinal degeneration—
may lead to RRD if retina tears.
Anomalous
• Colobomas—collie eye anomaly; abnormal 
retina around colobomatous optic nerve or 
large choroidal staphylomas may lead to RRD 
(merle ocular dysgenesis). • Severe retinal 
dysplasia, or oculoskeletal dysplasia (Labrador 
retrievers, Samoyeds). • Canine multifocal 
retinopathy. • Multiple ocular anomalies.
Metabolic
• Hyperviscosity (e.g., due to hyperprotein -
emia from multiple myeloma or other causes). • Polycythemia. • Shock. • Dogs—systemic 
hypertension, hypothyroidism, hypercho -
lesterolemia . • Cats—systemic hypertension 
(usually related to hyperthyroidism, chronic 
• Primary or metastatic. • Multiple myeloma, 
lymphoma, and intraocular masses (e.g., 
ciliary body adenocarcinoma or melanoma). 
• Pheochromocytoma may cause hyper- 
tension.
• Infectious retinitis or chorioretinitis may 
cause focal or diffuse detachment. • Infection 
may extend from or to the CNS.
Immune-Mediated/Inflammatory
• Immune complex disease—vasculitis or 
inflammation can result in exudative 
detachment: ◦ Dogs—systemic lupus 
erythematosus (SLE); uveodermatologic 
syndrome, meningoencephalitis of unknown 
etiology. ◦ Cats—periarteritis nodosa; SLE.
• If all other causes are ruled out, including 
retinal tears. • Idiopathic steroid-responsive 
detachment—reported in giant-breed dogs; 
may occur in any breed.
Trauma and Toxic
• Penetrating injury or foreign body. • Severe 
blunt trauma with inflammation or 
hemorrhage, usually unilateral. • Surgical 
trauma—if lens or vitreous disturbed (e.g., 
cataract surgery), can lead to RRD. • Toxic—
drug reactions (e.g., trimethoprim-sulfa, 
ethyelene glycol, griseofulvin [cats]).
• Systemic hypertension. • Old age—retinal 
thinning, severe vitreal degeneration. 
• Hypermature, intumescent cataracts that 
may rupture (e.g., diabetic cataracts). 
• Luxated lenses. • Lens extraction. 
• Hereditary—young dogs that have more 
severe retinal dysplasia and/or multiple ocular 
  DIAGNOSIS
neuritis, glaucoma, cataracts, progressive 
retinal atrophy, sudden acquired retinal 
degeneration syndrome (SARDS; see Retinal 
Degeneration), CNS disease. • Dilated pupil 
with slow or absent pupillary light reflexes—
glaucoma, oculomotor nerve lesion, optic 
neuritis, progressive retinal atrophy, SARDS. 
• Membrane or vessels associated with or 
behind lens—persistent tunica vasculosa 
lentis, persistent pupillary membranes, 
fibrovascular membrane due to intraocular 
neoplasia or inflammation.

1196  Blackwell’s Five-Minute Veterinary Consult  
RCBC/BIOCHEMISTRY/URINALYSIS
Typically normal, unless systemic disease 
present.
• Depends on suspected systemic problem.
• Protein electrophoresis or documentation of 
Bence Jones proteinuria. • Coagulation 
profile. • Bacterial culture of ocular or body 
fluids. • Thyroid hormone measurement. 
• Serologic or PCR testing for infectious 
diseases.
IMAGING
• Thoracic and abdominal radiographs, 
ultrasound, and/or CT. • Spinal radiographs 
may reveal bony changes consistent with 
multiple myeloma. • Ocular ultrasound—if 
ocular media is opaque, can identify retinal 
detachments or intraocular masses.
• Ophthalmic examination. • Serial blood 
pressure measurement—normal systolic 
arterial pressure <160 mmHg. • Cerebral 
spinal fluid tap—indicated if CNS disease or 
optic neuritis. • Vitreocentesis or subretinal 
fluid aspirate—if other testing fails to 
determine cause and infection or neoplasia is 
suspected; may aggravate inflammation or 
induce hemorrhage.
• Retina separated from the RPE and 
choroid. • May note masses, subretinal 
exudate, or etiologic infectious organism. 
• Chronic—retinal atrophy and tombstone 
appearance to RPE.
  TREATMENT
• Usually outpatient; depends on condition 
of patient. • Vision may be restored if 
underlying cause is rapidly identified and 
treated, but degeneration occurs quickly.
• May be a sign of systemic disease. • If 
associated with vitreal degeneration, lens 
luxation, or cataract surgery, fellow eye at 
risk for same condition. • Blind pets can 
adapt remarkably well and live a good-
quality life.SURGICAL CONSIDERATIONS
• RRD—may be surgically repaired by an 
ophthalmologist. • Laser retinopexy—may 
reverse detachments associated with optic disc 
colobomas; may stabilize partial/small 
detachments. May prevent detachment in 
predisposed fellow eye.
• Depends on underlying systemic cause. 
• Prednisone for immunosuppression (for 
immune-mediated causes) 2–4 mg/kg PO, 
divided q12 for 3–10 days (dog, cat), then 
taper slowly over months (do not exceed 
80 mg per day). Rule out systemic mycosis 
prior to use; may facilitate retinal reattach -
ment. • Corticosteroids at anti-inflammatory 
(dog), prednisolone 1–2 mg/kg PO q24h 
(cat), then taper; may be useful for exudative 
detachments of an infectious nature as long as 
the underlying disease is being definitively 
treated. • Antihypertensive agents—
amlodipine 0.1–0.5 mg/kg PO q12–24h 
(dog); 0.625–1.25 mg/cat PO q12–24h (cat). 
Consult with internist or cardiologist if 
persistent hypertension.
Systemic corticosteroids—do not use unless 
systemic mycosis is ruled out or is being 
definitively treated.
Adjunctive immunosuppressive therapy 
(azathioprine, cyclosporine, mycophenolate, 
leflunomide) may be needed in some 
immune-mediated retinal detachment if 
prednisone is not effective or tolerated long 
term.
  FOLLOW-UP
• Some immunosuppressive therapy (e.g., 
azathioprine) requires regular CBC and 
serum biochemistry analysis to monitor for 
bone marrow suppression or hepatotoxicity. • Serial blood pressure monitoring in 
hypertensive patients.
• Permanent blindness. • Cataracts. 
• Glaucoma—if eye becomes blind and 
painful enucleation may be necessary. 
• Chronic ocular pain. • Death secondary to 
systemic disease/neoplastic process.
• Prognosis for vision with complete 
detachment—guarded. Exception is hyper -
tensive retinopathy that is diagnosed and 
treated promptly. • Surgical reattachment of 
retina is about 72% successful at restoring 
vision for up to 1.5 years. • Vision may 
return if underlying cause is removed and 
reattachment occurs. • Blindness—may 
develop in days to weeks even with 
reattachment (more likely and rapid with 
exudative than serous detachments). • Focal 
or multifocal chorioretinitis—does not 
markedly impair vision; will leave scars.
• T rauma.
• Vitreous abnormalities.
• Primary neurologic disease or systemic 
disease affecting CNS.
• PLR = pupillary light reflex.
• RPE = retinal pigment epithelium.
• RRD = rhegmatogenous retinal 
• SLE = systemic lupus erythematosus.
Ophthalmology, 5th ed. St. Louis, MO: 
available onlineRetinal Detachment  (continued)

Canine and Feline, Seventh Edition  1197
RRetinal Hemorrhage
  BASICS
• Focal or generalized areas of bleeding into 
part or all layers of the retina.
• May be acute or chronic.
• T rauma-induced retinal detachments may 
tear retinal blood vessels.
• Intoxications, vasculitis, coagulopathy 
(including thrombocytopenia or thrombo -
cytopathia), neoplasia, and systemic infectious 
disease may cause focal or widespread 
• Systemic hypertension may cause local 
hemorrhage with vascular abnormalities and/
or complete or partial retinal detachments.
• Congenital malformations, concurrent 
vascular abnormalities, and neovascularization 
syndromes.
• Diabetes mellitus may be associated with 
retinopathy that includes vascular micro -
aneurysms with accompanying hemorrhage.
GENETICS
• Collie eye anomaly—autosomal recessive trait.
• Retinal dysplasia—suspected to be auto  - 
somal recessive inheritance.
• Retinal detachment—depends on causative 
factor, hereditary when observed in 
conjunction with above conditions.
• Common in hypertensive retinopathy of 
elderly cats.
• Common nonspecific finding with many 
systemic diseases.
Species
Dog and cat—any breed, age, or sex.
• May have genetic basis (e.g., collies with 
collie eye anomaly, Labrador retrievers with 
congenital vitreoretinal dysplasia).
• Hereditary breed-specific congenital defects 
that might cause detachment or severe retinal 
dysplasia—collies and Shetland sheepdogs with 
collie eye anomaly, Australian shepherd dogs 
with merle ocular dysgenesis, Labrador retrievers, 
Sealyham terriers, Bedlington terriers, and 
English springer spaniels with retinal dysplasia, 
and miniature schnauzers with retinal dysplasia 
and persistent hyperplastic primary vitreous.
• Old cats are often affected by systemic 
hypertension.• Congenital defects can be observed in 
puppies at 5–7 weeks.
SIGNS
Depend on underlying causes such as 
inflammatory disease in the posterior 
segment, systemic disease, or ocular 
• Often none.
• Vision loss, bumping into objects.
• Light or dark red appearance of the 
posterior segment.
• Blood-filled anterior chamber (hyphema).
• Evidence of bleeding elsewhere—petechia, 
ecchymoses, melena, hematuria.
• Leukocoria (whitish-appearing pupil) 
with or without reddish coloration behind 
the lens.
• Absence of menace response.
• Abnormal pupillary responses.
CAUSES
• Retinal detachment secondary to severe 
congenital malformations in the eye.
• Vitreoretinal defects (e.g., persistent 
hyperplastic primary vitreous [PHPV] or 
persistent hyperplastic tunica vasculosa lentis 
[PHTVL]).
• Retinal defects in geographic or complete 
retinal dysplasia or in partial or complete 
Acquired
• T rauma.
• Systemic hypertension—renal disease, 
cardiac disease, hyperthyroidism, hyper -
adrenocorticism, idiopathic.
• Intoxication—anticoagulant rodenticides; 
sulfonamide or estrogen-related compound 
toxicity causing thrombocytopenia.
• Infectious— Rickettsia rickettsia , 
Ehrlichia  spp., systemic mycoses 
(cryptococcosis).
• Neoplasia—lymphosarcoma, multiple 
myeloma (hyperviscosity).
• Hematologic disorders—coagulopathy 
(hemophilia, hepatic failure), 
thrombocytopenia, thrombocytopathia (von 
Willebrand disease), polycythemia.
• Diabetic retinopathy.
• Systemic hypertension or renal disease.
• Hematologic disease, coagulopathy.
• Vascular membranes.  DIAGNOSIS
• Normal choroidal vessel pattern in a 
subalbinotic fundus—seen in lightly 
pigmented eyes. Blood is contained in 
vascular channels and not outside of the 
vessels.
• Vitreal opacities:
◦ Vitreal hemorrhage (reddish coloration of 
the pupil, impossible to rule out concurrent 
retinal hemorrhage).
◦ Vitreal inflammation (generalized or local 
blurring or lack of fundus detail, usually no 
reddish coloration).
◦ Persistent hyaloid arteries.
◦ Neoplasia—especially lymphoma or 
ciliary body tumors.
◦ Also caused by uveitis, glaucoma, lens 
luxation, trauma, foreign bodies, and spread 
from local or systemic infectious diseases.
• Pigment spots in retina that look like 
microhemorrhage. Will not change over time.
• Usually normal unless indicative of systemic 
disease.
• Hyperglycemia and/or glucosuria—
indicative of diabetes mellitus.
• Azotemia and/or proteinuria—renal disease 
(may cause systemic hypertension).
• Thrombocytopenia, anemia/polycythemia, 
hyperglobulinemia, or other changes 
consistent with hematologic disorders.
• Endocrine—thyroid and adrenal function 
testing.
• Infectious agents—serologic or urine 
antigen testing for infectious agents.
• Coagulation, von Willebrand factor antigen 
testing.
IMAGING
• Ocular ultrasound—evaluate position of 
lens and retina in cases with blood-filled 
metastatic neoplasia or fungal disease.
• Abdominal ultrasound—if systemic disease 
or neoplasia suspected.
usually permits diagnosis of complete retinal 
detachment with partial retinal hemorrhage; 
detached neuroretina may often be visualized 
through the pupil as a whitish veil of tissue.
• Indirect ophthalmoscopy—diagnosis of 
funduscopic and vitreal changes.
• Vitreous paracentesis and cytologic 
examination—aid in the diagnosis for 
suspected neoplasia or mycotic disease.

1198  Blackwell’s Five-Minute Veterinary Consult  
R• Blood pressure measurement—indicated in 
all patients with severe retinal and vitreal 
• Findings include preretinal, intraretinal, or 
subretinal hemorrhage that may be focal or 
extensive.
• Secondary morphologic changes include 
fibrotic areas with proliferation of cellular 
extensions into the subretinal space, intra  - 
retinal, and thickening of the external 
limiting membrane.
  TREATMENT
• Infections and intoxications—require 
specific treatment. Systemic hypertension 
should be treated in a timely fashion to 
improve chances of retinal reattachment.
• NURSING CARE
Supportive care often needed.
ACTIVITY
Retinal detachment due to trauma—cage rest 
until the retina is reattached.
DIET
Possible dietary recommendations if the 
primary disorder is due to hepatic or renal 
disease.
• Discuss living with a blind dog or 
euthanasia of young puppies with severe 
bilateral hemorrhage due to congenital 
• Advise client that unilaterally affected dogs 
can function as pets but should not be used 
Surgery—referral to an ophthalmologist for 
vitrectomy and/or reattachment surgery.
• Corticosteroids—if workup is declined and 
infectious disease is unlikely: prednis(ol)one 
1–2 mg/kg/day PO for 7–14 days, then taper; 
long-term treatment of 4–6 weeks; especially 
for traumatic retinal detachment.
• Doxycycline 4 mg/kg PO q12h for 14–21 
days, or other appropriate systemic antibiotic 
based on infectious disease testing.• Primary systemic hypertension—
amlodipine 0.1–0.25 mg/kg PO q24h (dog); 
0.625–1.25 mg/cat PO q24 (cat); also 
consider angiotensin-converting enzyme 
inhibitor (see Hypertension, Systemic 
Arterial).
• Itraconazole, fluconazole—for crypto -
coccosis or other systemic mycosis (see 
Cryptococcosis or other specific mycoses).
• Besides corticosteroids, other immuno -
suppressive medications to treat immune-
mediated disease include mycophenolate, 
azathioprine, or leflunomide.
Systemic corticosteroids and other immuno -
suppressive drugs—use with caution in 
patients with systemic infection, do not 
coadminister with nonsteroidal anti-
inflammatory drugs.
Azathioprine may result in myelosuppression, 
hepatotoxicity, and gastrointestinal upset.
  FOLLOW-UP
• Repeated monitoring—required to ensure 
that condition subsides and retinal 
morphology normalizes.
• Preretinal hemorrhages—usually absorbed 
within a few weeks to several months if 
localized.
• Larger or repeated hemorrhages—may be 
followed by fibroplastic processes; may lead to 
the formation of fibrous preretinal membranes 
and vitreoretinal adhesions, which may cause 
vitreoretinal traction and retinal detachment.
• Intraretinal hemorrhage—reabsorbed 
within several weeks to months; may produce 
retinal scarring.
• Impaired vision.
• Most retinal hemorrhagic lesions are small, 
observed during routine ophthalmoscopic 
examination, usually heal rapidly, and cause 
no visual problems.
• Retinal hemorrhage due to systemic diseases 
or retinal malformations is more serious; most 
have an uncertain prognosis.  MISCELLANEOUS
• T rauma—may have other injuries; 
traumatic brain injury.
• Hypertension—cardiac, renal disease, 
hyperthyroidism, or hyperadrenocorticism.
• Coagulopathy—hypovolemic shock, 
internal bleeding.
• Cryptococcus infection—concurrent 
leptomeningitis and pneumonitis.
• Neoplasia—various other organ system 
• Hematologic disorders—hemorrhage and 
anemia.
• Secondary cataracts—may develop within 
weeks after the onset of diabetes mellitus in 
dogs.
• May occur at any age.
• Congenital or developmental diseases 
usually recognized in younger animals.
• Dogs with hereditary retinal disease should 
• Corticosteroids and immunosuppressive 
drugs may cause complications with 
SEE ALSO
• Hyphema.
• PHPV = persistent hyperplastic primary 
vitreous.
• PHTVL = persistent hyperplastic tunica 
Ofri, R. Diseases of the retina. In: Maggs DJ, 
Ophthalmology, 6th ed. St. Louis, MO; 
Elsevier, 2018, pp. 347–371.
Wiley & Sons, 2013.
available onlineRetinal Hemorrhage  (continued)

Canine and Feline, Seventh Edition  1199
RRhinitis and Sinusitis
  BASICS
• Rhinitis—inflammation of nasal epithelium. 
• Sinusitis—inflammation of paranasal 
sinuses; includes frontal sinus and maxillary 
recess in dogs; frontal and sphenopalatine 
sinuses in cats. • The nasal cavity communi­
cates directly with the sinuses; thus rhinitis 
and sinusitis often occur together.
Inflammation and irritation stimulate serous 
glandular secretion in the nasal mucosa. 
Opportunistic bacterial infections develop in 
compromised nasal mucosa causing discharge 
to become mucoid or mucopurulent. The 
inflammatory process can lead to turbinate 
destruction and erosion of the vasculature 
that results in epistaxis.
• Respiratory—sneezing and nasal discharge 
usually indicate upper respiratory tract 
disease. • Nervous—fungal and neoplastic 
disease can destroy the cribriform plate and 
invade the brain. • Ocular—epiphora with 
inflammation or obstruction of the 
nasolacrimal ducts. Conjunctivitis, keratitis, 
and/or corneal ulcerations with feline 
herpesvirus type 1 (FHV ­1)­related disease. 
Chorioretinitis with canine distemper or 
Cryptococcus . • Oral cavity—calicivirus, feline 
leukemia virus (FeLV), and feline immuno­
deficiency virus (FIV) are associated with 
stomatitis, glossitis, faucitis. Tooth root 
abscess, oronasal fistula or cleft palate 
possible.  • Lymphatics—medial retro­
pharyngeal lymphadenopathy possible with 
infectious and neoplastic sinonasal disease.
• Primary bacterial rhinosinusitis is rare; 
secondary infection from dental disease 
common or in association with chronic 
rhinitis. • Cats—chronic rhinosinusitis 
common. • Dogs—neoplasia, inflammatory 
rhinitis (lymphoplasmacytic rhinitis), fungal 
disease common. Nasal foreign body may 
cause acute sneezing.
GEOGRAPHICAL DISTRIBUTION
Chronic Fungal Rhinitis
• Aspergillus  and Penicillium  spp.—
worldwide. • Rhinosporidium seeberi —
mostly India, Africa, and South America. 
• Blastomycoses dermatitidis —endemic to 
North America: Pacific Northwest, Great 
Lakes region, Mississippi, Ohio, Missouri, 
Tennessee, and St. Lawrence river valleys. 
• Cryptococcus neoformans —worldwide.
Species
• Brachycephalic cats more prone to chronic 
rhinitis and Aspergillus  infection. 
• Dolichocephalic dogs more prone to 
Aspergillus  infection and nasal tumors.
• Cats—acute viral rhinosinusitis and 
nasopharyngeal polyps more common in 
young kittens (6–12 weeks). • Congenital 
diseases (cleft palate, ciliary dyskinesia) more 
common in young animals. • Neoplasia and 
dental disease—older animals. • Foreign 
bodies more common in young dogs.
SIGNS
• Sneezing, nasal discharge, epistaxis. 
• Discharge usually is serous initially and 
becomes mucoid, mucopurulent, serosanguinous, 
or hemorrhagic. • Unilateral discharge suggests 
foreign body, tooth root abscess, early neoplasia, 
or early fungal infection. Idiopathic inflamm­
atory rhinitis can also present with unilateral 
signs. • Bilateral discharge more common with 
viral or bacterial rhinosinusitis, inflammatory 
rhinitis, pharyngeal disease, or congenital 
abnormalities. Chronic presentation of neoplasia 
or fungal rhinitis is often bilateral. • Facial 
deformity or facial pain—usually with fungal 
or neoplastic disease. • Reverse sneezing more 
common in dogs, inappetence more common 
in cats.
• Check for decreased nasal air flow, bilateral 
or unilateral. • Evaluate oral cavity for tooth 
root abscess, oronasal fistula, cleft palate or 
ulcers. • Look for epiphora, conjunctivitis. 
Horner’s syndrome can be seen with middle 
ear disease. • Fundic examination—
chorioretinitis possible with infectious 
diseases; hypertension can result in tortuous 
retinal vessels or hemorrhage, platelet 
abnormalities can be associated with retinal 
hemorrhage or petechiation.
CAUSES
Dogs
Primary Inciting Causes
• Intranasal neoplasia—adenocarcinoma 
most common (31.5%); others include 
lymphoma, chondrosarcomas, or osteo­
sarcomas. • Fungal disease— Aspergillus 
fumigatus  most common. Penicillium  spp., 
Rhinosporidium seeberi , Blastomycoses 
dermatitidis , Cryptococcus neoformans  are rare 
causes. • Tooth root abscess. • Foreign body.  
palate or primary ciliary dyskinesia. 
• Parasitic causes—nasal mites 
(Pneumonyssoides caninum ), Capillaria 
aerophila, Eucoleus boehmii .  • Immune ­
mediated rhinitis—allergic rhinitis rare, idiopathic lymphoplasmacytic rhinitis more 
common. • Other infectious diseases include 
canine distemper or Bordetella bronchiseptica . 
• Local trauma can cause bone or turbinate 
deformity and predispose to chronic rhinitis 
or Aspergillus  infection. • Nasopharyngeal 
stenosis can be congenital or acquired.
Secondary Causes
• Lower airway disease or vomiting can result 
in nasal signs through nasopharyngeal 
regurgitation. • Nasal discharge can occur 
with eosinophilic bronchopneumopathy.  
• Epistaxis can be related to hypertension, 
thrombocytopenia, thrombocytopathia, or 
rarely other coagulopathies; trauma or foreign 
body also possible.
Cats
• Viral infections—FHV ­1 and calicivirus 
account for 90% of acute infections in kittens. 
• Bacteria— Bordetella bronchiseptica  is 
uncommonly a primary pathogen. 
• Neoplasia—adenocarcinoma and lymphoma 
most common. • Fungal disease— Cryptococcus 
neoformans  most common, Aspergillus felis , 
Penicillium , Microsporum canis  (rare). 
• Nasopharyngeal polyps in young cats. 
• Nasopharyngeal stenosis—congenital or 
secondary to chronic infection or inflammation. 
• Tooth root abscess or oronasal fistula. 
• Foreign bodies. • Congenital abnormalities 
include cleft palate.
• Opportunistic infection with bacteria can 
complicate viral rhinosinusitis. • Epistaxis due 
to coagulopathy or hypertension. • Aspiration 
of vomitus into the nasopharynx.
• Dolichocephalic breeds—fungal disease. 
• Brachycephalic cats—rhinosinusitis.
  DIAGNOSIS
Rule out secondary causes of rhinitis including 
coagulopathy and hypertension for epistaxis, 
lower airway disease, chronic vomition.
• Hemogram is nonspecific—may show 
leukocytosis (neutrophilia or eosinophilia) 
with infectious agents. Regenerative anemia 
with severe blood loss from coagulopathy. 
Nonregenerative anemia with chronic 
disease or neoplasia. Thrombocytopenia seen 
with coagulopathies or severe blood loss. 
• Serum biochemistry and urinalysis 
typically normal.
• PCR testing for viral etiologies. • FeLV and 
FIV serologic tests. • Oropharyngeal, 
conjunctival, and nasal swabbing in cats for

1200  Blackwell’s Five-Minute Veterinary Consult  
Rvirus isolation and bacterial culture. • Latex 
agglutination test for cryptococcal capsular 
antigen. • Aspergillus  titers—agar gel immuno­
diffusion (AGID) in dogs: false negatives 
possible, false positives uncommon; ideally 
combine AGID with nasal tissue culture/biopsy 
or direct visualization. ELISA in cats—high 
sensitivity and specificity for disease. 
• Coagulation profile if epistaxis present.
IMAGING
• Radiography—chest radiographs if lower 
airway disease or neoplasia suspected. 
• Dental radiographs highly sensitive for 
detecting periodontal disease. • Skull 
radiographs—loss of turbinate structures can 
be seen with all causes of rhinosinusitis. 
Open ­mouth or intraoral ventrodorsal views 
avoid superimposition of the mandible. 
• Nasopharyngeal polyps occasionally seen 
within the nasopharynx. • CT/MRI—
superior to plain radiography in evaluating 
the extent of disease and assessing the 
integrity of the cribriform plate. Also useful 
in evaluating disease of the palate, naso­
pharyngeal meatus, maxillary sinus, 
periorbital tissues, middle ear canal, and for 
presence of medial retropharyngeal 
Evaluate for hypertension if epistaxis.
Lymph Node Aspirate
Can be diagnostic for neoplasia or 
Cytology
Nasal swab may reveal Cryptococcus .
Culture
• Usefulness of bacterial culture is 
controversial since most animals have 
secondary bacterial infection. Potential 
bacterial pathogens are more commonly 
isolated in cats. • Fungal culture of a plaque 
lesion visualized on endoscopy aids in 
diagnosis of aspergillosis. • Asymptomatic 
intranasal carriage of Cryptococcus  possible.
Endoscopy
• An otoscope evaluates only the rostral nasal 
cavity. A rigid endoscope can be guided to the 
ethmoid turbinates, flexible endoscope provides 
good visualization rostrally, and can be 
retroflexed in the nasopharynx to visualize the 
caudal choanae. • Guided biopsy is possible 
with rigid and flexible endoscopy. Other 
techniques include core or blind pinch biopsies.
Surgery
Exploratory rhinotomy most invasive 
diagnostic tool, can be required for difficult 
foreign body or mass removal, if endoscopy is 
unsuccessful. Rarely required to obtain a 
definitive biopsy sample.PATHOLOGIC FINDINGS
Chronic inflammation causes turbinate 
resorption, mucosal ulceration and necrosis. 
Lymphoplasmacytic infiltrate indicates 
chronicity, neutrophilic usually signifies acute 
component. Neoplasia and fungus also cause 
bony lysis or destruction.
  TREATMENT
Overcrowded shelters and hoarding 
conditions increase stress and exposure to 
infectious pathogens.
Humidification can aid in moistening and 
mobilizing nasal secretions. Saline intranasal 
drops helpful if tolerated. Keep nares clean of 
obstructive mucus.
DIET
Malnutrition is common in young kittens 
with infectious causes of rhinitis. Appetite 
stimulants may be helpful.
Signs of chronic rhinitis can be variably 
controlled but are rarely eliminated.
• Rhinotomy is reserved for obtaining a 
biopsy or foreign body/mass removal when 
endoscopic intervention is unsuccessful. 
Rarely provides an advantage over endoscopy.  
• Surgery useful for polyp removal, dental ­
related nasal disease (tooth root abscess, 
oronasal fistula, cleft palate).
Antibiotics help control secondary bacterial 
rhinitis. Selection of antibiotic is mainly 
empirical. Long ­term use often needed.
Antifungals
See Cryptococcosis and Aspergillosis chapters 
for detailed treatment discussion.
l-Lysine
Inhibits FHV ­1 replication; may be useful—  
250 (kitten)–500 (cat) mg PO q12h.
Anti-inflammatory Agents
Piroxicam (NSAID) or more commonly 
meloxicam used for palliation of nasal tumors 
(via COX ­2 inhibition), either as sole agent 
or in conjunction with chemotherapy.
Steroids
Consider use with chronic rhinosinusitis in 
cats or lymphoplasmacytic rhinitis in dogs at anti­inflammatory doses when mucus 
obstruction limits appetite.
Efficacy is debated; unlikely helpful.
Antiparasitics
Ivermectin 300  μg/kg PO or SC once weekly 
for 3–4 treatments or milbemycin oxime 
1 mg/kg PO once weekly for 3 weeks for 
treatment of nasal mites.
Avoid chronic steroid use.
• NSAIDs can cause gastrointestinal 
ulceration. • Tetracycline may stain teeth of 
Use of NSAIDs and corticosteroids together 
is contraindicated.
N/A
  FOLLOW-UP
Patients taking oral azole antifungal 
medication typically require monthly 
biochemistry monitoring of hepatic values.
Vaccinations in kittens can lessen severity and 
duration of viral infection.
• Extension of fungal or neoplastic invasion 
into brain. • Seizures and other neurologic 
signs are possible if topical antifungal therapy 
is used when the cribriform plate is not 
intact.
• Dependent on etiology and extent of 
disease. • Acute viral/bacterial rhinitis—
good prognosis; chronic rhinitis—guarded 
for control of signs. • Fungal—fair to 
guarded prognosis depending on 
invasiveness and response to therapy. 
• Neoplastic—3–5 months prognosis 
with no treatment; 9–23 months with 
radiation therapy.
Infectious upper respiratory tract disease is a 
common cause of morbidity and mortality in 
stray and shelter kittens.Rhinitis and Sinusitis  (continued)

Canine and Feline, Seventh Edition  1201
RZOONOTIC POTENTIAL
Cryptococcus , Aspergillus , Penicillium  are 
transmissible to humans via shared 
environment. No direct transmission.
SYNONYMS
Nasosinusitis, rhinosinusitis, sinonasal.
SEE ALSO
• Aspergillosis, Disseminated Invasive
• Nasal Discharge.• Respiratory Parasites.
• AGID = agar gel immunodiffusion. 
• FeLV = feline leukemia virus. 
• FHV = feline herpesvirus.  • FIV = feline 
immunodeficiency virus.
Belda B, Petrovitch N, Mathews KG. 
Sinonasal aspergillosis: outcome after 
topical treatment in dogs with cribriform 
plate lysis. J Vet Intern Med 2018, 
32(4):1353–1358.Reed N. Chronic rhinitis in the cat. Vet Clin 
44(1):33–50.
Author  Adrienne M. Barchard Couts
acknowledge the prior contribution of Carrie 
J. Miller and Lynelle R. Johnson.
available online(continued)  Rhinitis and Sinusitis

R
1202  Blackwell’s Five-Minute Veterinary Consult  
RRight Bundle Branch Block
  BASICS
Conduction delay or block in the right 
bundle branch resulting in late activation of 
the right ventricle; the block can be complete 
or incomplete.
• A right axis deviation and wide QRS (≥0.08 
seconds in dogs; ≥0.06 seconds in cats) in 
• Large, wide S waves in leads I, II, III, and 
aVF .
• Incomplete right bundle branch block has 
right axis deviation with normal width QRS 
• The right bundle branch is anatomically 
vulnerable to injury because it is a thin strand 
of tissue and has a long undivided course.
• No hemodynamic compromise.
GENETICS
N/A
• Dog—most frequent form of intra­
ventricular conduction defect.
• Cat—not as frequent as left anterior 
fascicular block.
N/A
Species
In beagles, incomplete right bundle branch 
block can result from a genetically determined 
localized variation in right ventricular wall 
N/A
SIGNS
not cause hemodynamic abnormalities.
• Observed signs, if any, are usually associated 
with the underlying condition.
• Splitting of heart sounds because of 
asynchronous activation of ventricles in some 
patients.
• Does not cause signs of hemodynamic 
CAUSES
• Occasionally seen in normal and healthy 
dogs and cats.• Congenital heart disease.
• Chronic valvular fibrosis.
• After surgical correction of a cardiac defect.
• T rauma.
• Chronic infection with Trypanosoma cruzi  
(Chagas’ disease).
• Acute thromboembolism.
• Hyperkalemia (most commonly in cats 
with urethral obstruction).
N/A
  DIAGNOSIS
• Right ventricular enlargement—absence of 
right ventricular enlargement on thoracic 
radiographs or echocardiogram supports a 
diagnosis of right bundle branch block.
• Can also be confused with ventricular ectopic 
beats (especially if the block is intermittent), but 
consistent PR intervals and no pulse deficits 
with right bundle branch block.
• No specific changes.
• Serum potassium may be extremely high in 
cats with urethral obstruction.
• Occult heartworm test may be positive in 
• Chagas’ indirect fluorescent antibody test, 
direct hemagglutination, and complement 
fixation test may be positive in dogs.
IMAGING
disease; absence of right heart enlargement 
supports diagnosis of right bundle branch block.
show masses or pulmonary metastatic lesions; 
traumatic injuries could cause localized or 
diffuse pulmonary densities.
• Electrocardiography (ECG).
• Echocardiography.
surface in the path of the right bundle branch; 
surface within 2 hours post ­mortem gives clear 
visualization of the conduction system.
  TREATMENT
Direct treatment toward the underlying 
N/A
ACTIVITY
DIET
• Does not cause hemodynamic abnormalities 
itself.
• The lesion causing the block could progress, 
leading to more serious arrhythmias or complete 
heart block.
N/A
None required unless needed to manage 
N/A
N/A
N/A
N/A
  FOLLOW-UP
Serial ECG may show resolution of the lesion 
or progression to complete heart block.
N/A
• The causative lesion could progress, leading 
to a more serious arrhythmia or complete 
• First­ or second ­degree AV block may 
indicate involvement of the left bundle branch.
N/A
N/A
N/A

Canine and Feline, Seventh Edition  1203
RR
N/A
SEE ALSO
Degree).
• Left Bundle Branch Block.ABBREVIATIONS
Williams and Wilkins, 1992.Tilley LP , Smith FWK, Jr. 
Electrocardiography. In: Smith FWK, Tilley 
LP , Oyama M, Sleeper M, eds., Manual of 
Canine and Feline Cardiology, 5th ed. 
St. Louis, MO: Saunders Elsevier, 2016, 
pp. 49–76.
Ames, IA: Wiley Blackwell, 2018.
II I III aVR aVL aVF CV5RL
Figure 1 .
Right bundle branch block in a dog. The electrocardiographic features include QRS duration of 0.08 seconds; positive QRS complex in aVR, aVL, and CV5RL 
(M­shaped); and large wide S waves in leads I, II, III, and aVF . There is a right axis deviation (approximately −110°) (50 mm/s, 1 cm = 1 mV). (Source: From Tilley 
LP . Essentials of Canine and Feline Electrocardiography, 3rd ed. Baltimore: Williams & Wilkins, 1992. Reprinted with permission of Wolters Kluwer.)
Figure 2.
Right bundle branch block in a cat with the dilated form of cardiomyopathy. The QRS duration is 0.08 seconds (4 boxes). Large and wide S waves are present in 
leads I, II, III, aVF , and CV6 LU. The QRS in CV5RL has a wide R wave (M ­shaped). There is a marked axis deviation (approximately −90°). Source: From Tilley 
LP . Essentials of Canine and Feline Electrocardiography, 3rd ed. Baltimore: Williams & Wilkins, 1992. Reprinted with permission of Wolters Kluwer.(continued)  Right Bundle Branch Block

R
1204  Blackwell’s Five-Minute Veterinary Consult  
RRocky Mountain Spotted Fever
  BASICS
A tick-borne disease, caused by Rickettsia 
rickettsii , that affects dogs and is considered 
the most important rickettsial disease in 
humans.
• Pathogen— Rickettsia rickettsia , a Gram-
negative, intracellular bacteria. • Vector—
various species of ticks including Dermacentor 
variabilis  (United States, east of Great Plains 
region), D. andersoni  (western United States 
and Canada) , Rhipicephalus sanguineus  
(throughout North and South America) , 
Amblyomma cajennense  (Latin America). 
• T ransmission—via saliva of the vector or by 
blood transfusion; tick must be attached for 
5–20 hours to infect host (humans, dogs, 
cats) or reservoir host (rodents and dogs). 
• Incubation period—2 days–2 weeks. 
• Infection—organism invades and multiplies 
in vascular endothelium; causes microvascular 
hemorrhage; platelet aggregation and antiplate -
let antibodies cause thrombocytopenia, 
widespread vasculitis results in increased 
vascular permeability, plasma loss into 
interstitial space, hypotension, and eventually 
shock and disseminated intravascular 
• Cardiovascular—vasculitis, hypotension, 
shock. • Hemic/lymphatic/immune—
hemorrhage due to thrombocytopenia and 
vasculitis; lymphadenopathy, splenomegaly. 
• Ophthalmic—conjunctivitis, scleral 
injection, retinal hemorrhage, anterior uveitis. 
• Skin/exocrine—multifocal edema, 
petechiae and ecchymoses, dermal necrosis. 
• Musculoskeletal—joint and muscle pain. 
• Nervous—meningoencephalitis: seizures, 
vestibular deficits, stupor, coma, cervical pain. 
• Respiratory—dyspnea, cough. • Renal/
urologic— vasculitis and prerenal azotemia 
from dehydration and shock.
GENETICS
N/A
• Tick season—late March through October.  
• Prevalence—overall infections in ticks <2%; 
varies by geographic location.
• United States— RMSF has been diagnosed 
in most states; highest infection rates in 
southeastern states. • North and South 
America.
Species
• Purebred dogs seem more prone to 
developing clinical illness than mixed-breed 
dogs. • German shepherd dogs—more 
common.
Any age
None
SIGNS
• Fever—within 2–3 days of tick attachment. 
• Lethargy, depression, anorexia. • Swelling 
(edema)—lips, scrotum, prepuce, ears, 
extremities. • Stiff gait—especially with 
scrotal or preputial edema. • Spontaneous 
bleeding—sneezing, epistaxis. • Respiratory 
distress, cough. • Neurologic—ataxia, head 
tilt, seizures. • Ocular pain.
• Clinical—variable in severity; lasts 2–4 
weeks untreated. • Ticks may still be present 
in acute cases. • Pyrexia. • Cutaneous 
lesions—edema of face, limbs, prepuce, 
scrotum. • Extremities—necrosis. 
• Conjunctivitis. • Scleral injection.
• Respiratory—dyspnea, exercise intolerance 
resulting from pneumonitis, increased 
bronchovesicular sounds. • Generalized 
lymphadenopathy. • Neurologic—vestibular 
dysfunction, altered mental status, seizures. 
• Myalgia/arthralgia. • Petechia, ecchymoses—  
ocular, oral, genital mucous membranes. 
• Hemorrhagic diathesis—epistaxis, melena, 
hematuria; in severe cases. • Cardiac 
arrhythmias. • DIC and death from shock—
in severe acute cases.
CAUSES
R. rickettsii  infection.
• Exposure to ticks. • Coinfection with other 
pathogens (tick-borne). • English springer 
spaniels with phosphofructokinase deficiency 
are prone to a more severe form of RMSF .
  DIAGNOSIS
• Canine ehrlichiosis— Ehrlichia canis ; not 
seasonal; can be clinically indistinguishable 
from RMSF (especially acute cases); 
differentiate with serologic testing; both 
respond to same treatment. • Primary 
immune-mediated thrombocytopenia—not 
usually associated with fever or lymphadeno -
pathy; differentiate by ruling out infectious 
causes; may treat for both until results are 
known. • Systemic lupus erythematosus—
antinuclear antibody titer usually negative 
with RMSF; serologic testing diagnostic. • Brucellosis—scrotal edema; serologic 
testing diagnostic.
CBC
• Thrombocytopenia ( ~ 40% of cases)—due 
to antiplatelet antibody and consumption; 
platelet counts frequently 25,000–250,000/ μL. 
• Mild anemia (normochromic, normocytic). 
• Mild leukopenia (early in infection), 
leukocytosis and monocytosis develop later.
• Usually nonspecific. • Hypoalbuminemia—  
increased vascular permeability 
• Hypercholesterolemia—consistently 
found; cause unknown • Mild increases in 
alanine aminotransferase, alkaline 
phosphatase, BUN, creatinine, and total 
bilirubin (rare). • Hyponatremia, hypo -
chloremia, and metabolic acidosis have also 
• Proteinuria—with or without azotemia; 
from glomerular/tubular damage. 
• Hematuria—coagulation defects.
• Several tests are available to measure serum 
antibodies including the micro-
immunofluorescence (micro-IF), ELISA, and 
latex agglutination tests. • Diagnosis by 
antibody measurement requires an increased 
(single) IgM titer, or a four-fold increase in 
IgG between acute and convalescent 
measurements. Paired IgG titers should be 
drawn 3 weeks apart and submitted for 
analysis at the same time. High antibody 
titers can be detected for up to 1 year after 
treatment. • Latex agglutination test—higher 
specificity, lower sensitivity than the micro-IF 
test. • PCR on whole blood and tissue 
specimens—detects DNA before 
seroconversion in some dogs.
IMAGING
Thoracic radiographs—diffuse interstitial 
pattern in patients with respiratory signs.
• Direct immunofluorescence—punch 
biopsies from affected lesions; allows early 
detection of rickettsial antigens. • CSF 
analysis—often normal; may show increased 
protein and polymorphonuclear and 
mononuclear cells.
• Widespread petechia, splenomegaly, and 
generalized hemorrhagic lymphadenopathy. 
• Necrotizing vasculitis with perivascular cell 
infiltration (mononuclear and neutrophilic). 
• Vascular lesions—most prominent in skin, 
kidneys, myocardium, meninges, retina, 
pancreas, gastrointestinal tract, and urinary 
bladder. • Hepatic and focal myocardial 
necrosis, nodular gliosis in brain, and

Canine and Feline, Seventh Edition  1205
RRinterstitial pneumonia. • Special stains—to 
identify organisms.
  TREATMENT
Inpatient management recommended until 
stable and showing response to treatment.
• IV fluid therapy—correct dehydration; use 
caution; excessive fluid therapy can worsen 
edema. • Blood transfusion—for patients 
with clinical signs of anemia. • Fresh whole 
blood or platelet transfusion—severe 
hemorrhage due to thrombocytopenia. 
• Provide analgesia for patients with muscle, 
joint, and severe skin involvement.
ACTIVITY
Restricted during acute illness.
DIET
N/A
• Prognosis—good in acute cases with 
appropriate and prompt therapy. • Response 
occurs within hours of treatment. • If 
treatment is not instituted until CNS signs 
occur or later in disease process, mortality is 
high; a patient with CNS signs may die 
within hours.
If surgery is required for other reasons, blood 
transfusion may be needed to correct anemia 
and/or marked thrombocytopenia.
• Doxycycline 10 mg/kg PO, IV q24h (or 
5 mg/kg PO, IV q12h) for 10 days; given IV 
if patient is vomiting. Extended doxycycline 
therapy was required to clear infection in one 
experimentally infected dog. • Enrofloxacin 
and chloramphenicol may also be used. 
• Prednisone—concurrent use; anti-
inflammatory or immunosuppressive dose; 
given early in course of disease does not seem 
to be detrimental to recovery. May alleviate 
immune-mediated thrombocytopenia and 
cerebral edema.CONTRAINDICATIONS
Renal insufficiency—do not use tetracycline 
due to renal excretion; doxycycline may be 
given (excreted via gastrointestinal tract).
• Tetracycline (or derivatives)— 
discoloration of teeth in patients <6 months 
old. • Enrofloxacin—articular cartilage 
damage can occur in young dogs. 
• Chloramphenicol— reduces titers to a 
greater extent than tetracyclines; warn client 
of human health risks; avoid use in dogs 
with thrombocytopenia, pancytopenia, 
or anemia.
None
• Chloramphenicol—puppies <6 months of 
age; 20 mg/kg PO q8h for 14 days; 
recommended to avoid discoloration of 
erupting teeth or in pregnant patients. 
• Enrofloxacin 10 mg/kg PO, IM, IV q24h 
for 7 days. • Oxytetracycline and tetracycline 
22 mg/kg PO q8h for 14 days.
  FOLLOW-UP
Monitor platelet count every 2–3 days until 
normal.
• Avoid tick-infested areas and control tick 
infestation on dogs. • Flea and tick collars, 
topical or enteral tick preventives—may 
reduce reinfestation. • Environment—tick 
eradication impossible; organism maintained 
in rodents and other reservoir hosts. 
• Manually remove ticks—use gloves (see 
Zoonotic Potential); ensure mouth parts are 
removed.
N/A
• Early antibiotic treatment—reduces fever 
and albumin extravasation; improvement 
within 24–48 hours. • Platelet counts—
should return to normal within 2–4 days after 
initiating treatment. • Serologic titers remain 
positive during convalescence. • Naturally 
infected dogs do not seem to become 
reinfected. • Acute cases—excellent prognosis with appropriate and early treatment. • With 
CNS disease—poor prognosis.
None
None
• Source of infection (humans)—ticks from 
wooded areas or carried into environment by 
dogs (RMSF not directly transmitted to 
humans by dogs), exposure to infectious 
material when removing infected ticks from 
dogs. • Clinical signs in humans are similar 
to those seen in dogs. • T reatment with 
tetracycline results in a rapid recovery, overall 
mortality rate is 2–10%.
N/A
• DIC = disseminated intravascular coagulation.
• Micro-IF = microscopic immuno  fluorescence.
• RMSF = Rocky Mountain spotted fever.
Allison RW, Little SE. Diagnosis of rickettsial 
diseases in dogs and cats. Vet Clin Pathol 
2013, 42:127–144.
Greene CE, Kidd L, Breitschwerdt EB. Rocky 
Mountain spotted fever. In: Greene CE, ed., 
pp. 259–267.
Levin ML, Killmaster LF , Zemtsova GE, et al. 
Clinical presentation, convalescence, and 
relapse of Rocky Mountain spotted fever in 
dogs experimentally infected via tick bite. 
PLoS ONE 2014, 9: e115105.
Warner RD, Marsh WW. Rocky Mountain 
spotted fever. J Am Vet Med Assoc 2002, 
221:1413–1417.
available online(continued)  Rocky Mountain Spotted Fever

1206  Blackwell’s Five-Minute Veterinary Consult  
RRodenticide Toxicosis—Anticoagulants
  BASICS
• Anticoagulant rodenticide intoxication 
results in a delayed-onset (3–5 days) 
coagulopathy caused by the reduction of 
vitamin K1-dependent clotting factors (II, 
VII, IX, X).
• There are two primary types of anticoagu-
lant rodenticides: first- and second-genera-
tion. First-generation anticoagulants, such as 
warfarin, are generally less toxic and shorter 
acting than second-generation which tend to 
persist longer in the liver and require 3–4 
weeks of antidote therapy.
• Anticoagulant rodenticides inhibit vitamin 
K1 epoxide reductase, DT-diaphorase, and 
possibly other enzymes involved in the 
reduction of vitamin K1 epoxide to vitamin 
K1.
• Vitamin K1 is required for carboxylation of 
clotting factors II, VI, IX, and X; uncarboxy-
lated clotting factors do not bind calcium 
sufficiently to participate in clot formation.
• Still common but fewer exposures.
• In 2011, the US Environmental Protection 
Agency (EPA) banned the use of second-
generation anticoagulants (i.e., brodifacoum, 
bromadiolone, difenacoum, and difethialone) 
for residential use unless placed by a pest 
control operator.
• In 2013, the EPA gave notice of cancelling 
registration and denial of future applications 
for certain rodenticide products including 
warfarin, brodifacoum, and difethialone. In 
response, manufacturers have begun the 
process of transition to non-anticoagulant 
baits such as bromethalin and cholecalciferol.
No breed or gender predilections; younger 
animals may ingest bait more readily.
SIGNS
• May be slightly more prevalent in the spring 
and fall when rodenticide products are used.
• Clinical signs typically begin 3–5 days after 
ingestion. Early signs maybe noted at 48 
hours.
• Use of anticoagulant rodenticides.
• Evidence of rodenticide dye in vomitus or 
feces.
• Coughing, dyspnea, tachypnea, or exercise 
intolerance are often the first clinical signs.• Bleeding from body orifices; subcutaneous 
or joint swelling, petechiation of the skin and 
gums may also be observed.
• Evidence of hemorrhagic shock (i.e., 
tachycardia, hypovolemia, hypotension, poor 
pulse quality, pallor).
• Coughing, dyspnea, tachypnea, pale 
• Hematomas—often ventral and at 
venipuncture sites; subcutaneous hematomas.
• Bleeding from body orifices, periorbital 
bleeding, scleral hemorrhage.
• Hemarthrosis, lameness.
• Exercise intolerance, lethargy, depression.
• Muffled heart or lung sounds.
• Distended abdomen (hemoabdomen).
CAUSES
Ingestion of anticoagulant rodenticides or, 
rarely, ingestion of prey that have been 
exposed to anticoagulant rodenticides (see 
Risk Factors).
• Dogs are much more sensitive to anti -
coagulant rodenticides than cats.
• Small doses over several days may add up to 
a toxic dose.
• Secondary or relay toxicosis by consumption 
of poisoned rodents is possible but unlikely.
• There is a wide range of toxicity between 
anticoagulant rodenticides. In general, if the 
ingestion exceeds 1/5–1/10 the LD50, 
decontamination and monitoring for 
coagulopathy are indicated.
• Dogs:
⚬ Brodifacoum, LD50 0.25–2.5 mg/kg.
⚬ Bromadiolone, LD50 11–20 mg/kg.
⚬ Chlorophacinone, LD50 50–100 mg/kg.
⚬ Difethialone, LD50 4 mg/kg.
⚬ Diphacinone, LD50 3–7.5 mg/kg.
⚬ Warfarin, LD50 20–50 mg/kg.
• Cats:
⚬ Brodifacoum, LD50 25 mg/kg.
⚬ Bromadiolone, LD50 >25 mg/kg.
⚬ Difethiolone, LD50 >16 mg/kg.
  DIAGNOSIS
• Congenital clotting factor deficiencies.
platelet count will reveal severe thrombo  - 
• Coagulation factor deficiency secondary 
to hepatic disease—assay for factor 
deficiencies (e.g., factor VII), liver function, 
bile acids.
• Disseminated intravascular coagulopathy 
which is typically associated with neoplasia, 
sepsis, pancreatitis, or concurrent disease. Lab 
evidence includes prolonged prothrombin 
time (PT), partial thromboplastin time (PTT), elevated fibrin degradation products, 
D-dimer with thrombocytopenia.
• Fat malabsorption.
• Hemorrhagic shock from trauma, 
neoplasia, bone marrow suppression, 
• Anemia with marked hemorrhage, often 
acute and nonregenerative.
• Thrombocytopenia, mild. Typically 
50,000–150,000 × 103/μL.
• Activated clotting time >150 seconds 
supports coagulopathy but is not specific for 
anticoagulant rodenticide poisoning.
• Prolonged PT and PTT support exposure 
to anticoagulant rodenticide; PT will be 
prolonged 6–18 hours earlier than PTT. 
These values will normalize with vitamin K1 
therapy.
• Protein-induced vitamin K absence or 
antagonist (PIVKA) assay, rarely used.
• Anticoagulant rodenticide detection in the 
blood or liver will confirm exposure to a 
specific product.
stomach or intestinal contents is not reliable 
due to the delay between consumption of bait 
and appearance of clinical signs.
IMAGING
• Thoracic radiography may reveal pleural 
effusion (i.e., hemothorax); multilobular, 
alveolar infiltration (i.e., pulmonary 
hemorrhage) or an enlarged cardiac silhouette 
(i.e., hemopericardium).
• Ultrasound of both the pleural and 
peritoneal cavities may reveal effusion 
consistent with hemorrhage.
Thoracentesis may confirm hemothorax.
• Free blood in the thoracic cavity, lungs, and 
abdominal cavity is a common post-mortem 
finding.
• Hemorrhage into the cranial vault, 
gastrointestinal tract, subcutaneous space, 
intramuscular space, and urinary tract is less 
common.
  TREATMENT
• Patients in acute crisis should be 
• Patients without active hemorrhaging or a 
stabilized coagulopathy may be treated on an 
• Vitamin K1 is antidotal at 2.5–5 mg/kg 
q24h or divided q12h. The preferred route of 
administration is oral; however, in case of a 
coagulopathic patient, the subcutaneous route

Canine and Feline, Seventh Edition  1207
Ris preferred due to the potential for limited 
gastrointestinal absorption. Use a small needle 
in multiple locations, if needed, and monitor 
for anaphylactoid reaction.
• T reat acute hemorrhagic shock with IV 
crystalloids, colloids, or blood products as 
needed. Initial crystalloid boluses of 
10–20 mL/kg can be given over 15–20 
minutes during stabilization. Repeat 2–3 
times as needed to increase blood pressure.
• Packed RBCs, whole blood, fresh frozen 
plasma, or frozen plasma may be necessary to 
replace coagulation factors.
• T reat life-threatening cardiac tamponade or 
hemothorax with pericardiocentesis or 
thoracocentesis as indicated. If the patient is 
stable and responding to treatment, these 
procedures should be avoided. With time, the 
blood will reabsorb.
Provide supportive care as needed.
ACTIVITY
Confine the patient until the coagulopathy is 
stabilized as activity enhances blood loss.
DIET
Feed a nutritious, high-quality protein diet to 
support coagulation factor synthesis.
• Warn client that reexposure, even months 
to years later, could be a serious problem due 
to persistence of second-generation antico-
agulants in the liver.
• Encourage the owner to pick up all loose/
unprotected bait on the property.
• Do not discontinue vitamin K1 therapy 
early, even if the patient is asymptomatic.
• Thoracentesis may be important for 
removing free thoracic blood, which causes 
dyspnea and respiratory failure (see 
Appropriate Health Care).
• The coagulopathy must be corrected before 
surgery.
Vitamin K1, 2.5–5.0 mg/kg PO q12h for 
5–7 days for most first-generation anticoagulants and PO q24h for 4–6 weeks 
for most second-generation anticoagulants; 
bioavailability may be enhanced by the 
concurrent feeding of a small amount of fat, 
such as canned dog food.
• Vitamin K3 is not efficacious in the 
treatment of anticoagulant rodenticide 
toxicosis and should not be used.
• IV vitamin K1 has been reported to cause 
anaphylactoid reactions. Avoid this route of 
• Minimize stress, trauma, jugular venipunc-
ture, and cystocentesis due to the risk of acute 
and catastrophic hemorrhage.
• Avoid large-bore hypodermic needles, 
unnecessary surgical procedures, and 
parenteral injections.
• Use the smallest possible needle when 
giving an injection or collecting samples.
Sulfonamides and phenylbutazone may 
displace anticoagulant rodenticides from 
plasma binding sites, leading to freer toxicant 
and increased risk of toxicosis.
  FOLLOW-UP
PT (preferred) test 2–3 days after the last dose 
of vitamin K1 to assess duration of therapy. If 
the PT is prolonged, administer another 1–3 
weeks of vitamin K1 and retest.
Prevent pet’s access to anticoagulant 
rodenticides by using bait stations and 
keeping stored bait in a secure location.
• Secondary bacterial pneumonia may occur 
following intrapulmonary hemorrhage.
• Intracranial and intra-articular hemorrhage 
may occur.
• Pregnant animals can abort due to placental 
hemorrhage and detachment.
If the patient survives the first 48–72 hours of 
acute coagulopathy, the prognosis improves.  MISCELLANEOUS
• Warfarin, diphacinone, and perhaps other 
anticoagulant rodenticides may pass into 
amniotic fluid and to the fetuses of an 
exposed pregnant animal. These toxicants 
may also pass via the milk and present 
concerns for nursing offspring. In general, 
antidotal treatment of the pregnant or 
nursing patient is recommended. 
Alternatively, nursing young may be 
weaned.
• EPA = US Environmental Protection 
Agency.
• PIVKA = protein-induced vitamin K 
absence or antagonist.
• www.petpoisonhelpline.com
• www.aspca.org/pet-care/
animal-poisoncontrol
Murphy MJ. Anticoagulants. In: Osweiler 
GD, et al., eds., Blackwell’s Five-Minute 
Veterinary Consult Clinical Companion 
Wiley-Blackwell, 2016, pp. 835–843.
Murphy MJ. Anticoagulant rodenticides. In: 
Gupta RC, ed., Veterinary Toxicology: Basic 
and Clinical Principles, 3rd ed. San Diego, 
CA: Elsevier, 2018, pp. 583–612.
available online(continued)  Rodenticide Toxicosis—Anticoagulants

1208  Blackwell’s Five-Minute Veterinary Consult  
RRodenticide Toxicosis—Bromethalin
  BASICS
OVERVIEW
• Bromethalin is a neurotoxic rodenticide 
that produces cerebral edema and elevated 
CSF pressure, resulting in progressive CNS 
depression, coma, paresis, and paralysis.
• Clinical signs and death have been reported in 
dogs and cats exposed to bromethalin at doses as 
low as 0.36 and 0.24 mg/kg, respectively.
• T rade names include Tomcat, Fastrac, Top 
Gun, Gladiator, and others. Bromethalin 
concentrations in products can vary from 
0.01 to 0.025%.
• Dogs and cats. Other species including 
humans may be affected.
• Any breed or age may be affected.
SIGNS
• Ingestion most often results in a delayed 
neurotoxic syndrome that develops within 
2–7 days of ingestion; however, delays of up 
to 2 weeks may occur.
• Common clinical signs include anorexia, 
progressive ataxia, paresis, and hind limb 
paralysis, moderate to severe central nervous 
system depression, fine muscle tremors, and 
focal motor or generalized seizures.
• Forelimb extensor rigidity and decerebrate 
postures are often seen.
• Ingestion of high doses of bromethalin less 
commonly results in an acute onset (within 
1–2 hours) of CNS excitation, muscle 
tremors, and seizures.
Bromethalin ingestion most often occurs in 
animals <1 year of age.
  DIAGNOSIS
Neurologic syndromes produced by trauma, 
neoplasia, cerebral vascular disorders, as well 
as infectious and other toxic agents.
Alterations in routine serum electrolytes and 
chemistries are not anticipated.
Analytical chemical confirmation of 
bromethalin residues in fresh frozen fat, liver, 
kidney, and brain tissue.
IMAGING
Neuroimaging (MRI) may reveal generalized 
brain edema.
• CSF generally reveals normal cytology, 
protein concentration, specific gravity, and 
cell count.• EEG findings can change during the course 
of the toxic syndrome and may include spike 
and spike-and-wave activity, marked voltage 
depression, and abnormal high-voltage 
slow-wave activities.
• Histologic lesions are generally confined to 
the CNS and include spongy degeneration in 
the cerebrum, cerebellum, brainstem, spinal 
cord, and optic nerve white matter due to 
myelin edema.
• Gross evidence of cerebral edema is 
generally mild.
  TREATMENT
• Aggressive early treatment with oral 
activated charcoal and a cathartic to reduce 
gastrointestinal absorption is warranted.
• Prolonged anorexia and may require 
supplemental feeding to maintain caloric 
intake.
• Use cage padding to reduce the risk of 
decubitus ulcer formation in recumbent 
animals.
• Gastrointestinal tract decontamination 
including early induction of emesis followed 
by administration of activated charcoal (1–2 
g/kg PO) with an osmotic cathartic (sorbitol) 
× 1 dose) followed by activated charcoal alone 
q6–8h × 24 hours. Pay attention to sodium 
concentration. The efficacy of these 
treatments remains unknown.
• Control of cerebral edema with mannitol 
500 mg/kg q6h slow IV bolus, dexamethasone 
1–2 mg/kg q6h IV, and furosemide 1–2 mg/kg 
q6h IV may have limited efficacy.
• Diazepam 0.5–1 mg/kg, IV as needed, or 
other anticonvulsants may be given to abolish 
severe muscle tremors and seizures.
• 20% IV lipid emulsions (ILE)—bolus dose 
1.5 mL/kg over 2–3 minutes; CRI of 
0.25 mL/kg/min for 30–60 minutes. Check 
serum q2h until it becomes clear; repeat as 
needed; if no clinical improvement after 
3 doses, discontinue. Other ILE dosing 
regimens can be used.
• Contraindications for the use of mannitol 
include renal disease, pulmonary edema, 
dehydration, and intracranial hemorrhage.
• Animals receiving mannitol therapy may 
become dehydrated.
• Rehydration may be associated with a 
worsening of clinical signs, possibly due to rebound cerebral and pulmonary edema. 
Maintenance of hydration is important and 
can be more safely accomplished through the 
administration of oral fluids.
• Adverse effects of ILE may relate to 
contamination of the lipid product or direct 
reaction to the emulsion.
  FOLLOW-UP
• May require several weeks to recover from 
mild poisoning.
• Prognosis is poor for the severely affected 
animals.
• Prevent ongoing rodenticide ingestion.
Relay toxicity arising from the consumption 
of animals poisoned with bromethalin may 
occur.
• EEG = electroencephalogram.
• ILE = IV lipid emulsion.
Khan SA and Schell MM. Bromethalin. 
Merck Veterinary Manual. Available at: 
https://www.merckvetmanual.com/
toxicology/rodenticide-poisoning/
bromethalin
DeClementi C, Sobczak BR. Common 
rodenticide toxicoses in small animals. Vet 
48:1027–1038.
Author  David C. Dorman

Canine and Feline, Seventh Edition  1209
RRodenticide Toxicosis—Cholecalciferol
  BASICS
Hypercalcemic disorder resulting from 
ingestion of vitamin D rodenticide 
• Cholecalciferol is metabolized to 25‐
hydroxycholecalciferol in the liver. 25‐ 
hydroxycholecalciferol is metabolized to 
several metabolites in the kidney, including 
calcitriol, the most potent metabolite in terms 
of enhancing calcium absorption from the gut 
and calcium resorption from bones under 
physiologic conditions.
• 1,25‐dihydroxycholecalciferol is the active 
metabolite of cholecalciferol under physi-
ologic conditions.
• Under toxic conditions, 25‐hydroxychole-
calciferol is the predominant circulating and 
active metabolite.
• 25‐hydroxycholecalciferol increases 
absorption of calcium from the gut, 
stimulates bone resorption, and enhances 
calcium absorption in renal distal tubules, 
resulting in hypercalcemia (serum calcium 
>12.5 mg/dL).
• Serum phosphorus is also increased.
• The outcome is metastatic and dystrophic 
mineralization of soft tissues, resulting in 
pathophysiology of the affected organs.
• Cardiovascular—mineralization, 
• Gastrointestinal—anorexia; mineralization; 
emesis; hematemesis; constipation; increased 
gastric acid secretion.
• Musculoskeletal—bone demineralization; 
muscle tremors.
• Nervous—seizures or depression.
• Renal/urologic—calcification, proximal 
tubular necrosis, dilute urine, and renal 
failure.
• Respiratory—lung mineralization; dyspnea.
• Cholecalciferol rodenticide toxicosis—most 
common cause of vitamin D poisoning in 
• Incidence of poisoning unknown but 
growing in popularity as rodenticide as the 
use of anticoagulant rodenticides declines.
• Suckling pups and kittens can be poisoned 
through milk.
Species
• Other species, particularly exotics.
All ages affected; younger dogs (<6 months) 
and cats are the most sensitive.SIGNS
Cholecalciferol rodenticides—signs develop 
within 12–36 hours post ingestion.
• Inactivity.
• CNS depression.
• Melena.
• Loss in body weight.
• Renal pain on palpation.
• Gastrointestinal hemorrhage.
• Oropharyngeal erosive lesions.
• Bradycardia; ventricular premature 
• Dyspnea.
CAUSES
Cholecalciferol rodenticides (0.075%)—
Quintox, Rampage, Ortho Rat‐B‐Gone, Ortho 
Mouse‐B‐Gone, others; clinically normal dogs 
and cats have developed hypercalcemia at 0.5 
mg/kg body weight; signs have occurred in 
dogs and cats at 0.1 mg/kg body weight.
• Preexisting renal, gastrointestinal, cardiac, 
lung, or CNS diseases.
• Granulomatous diseases (e.g., blastomycosis).
• Juvenile hypercalcemia.
• Age—young animals are most susceptible.
• Feline idiopathic hypercalcemia.
  DIAGNOSIS
• Other hypercalcemic disorders, including 
lymphosarcoma and other malignancies, hypoadrenocorticism, chronic renal failure, 
primary hyperparathyroidism, and granu-
lomatous lesions in soft tissues.
• Anticoagulant rodenticide and nonsteroidal 
anti‐inflammatory drug (NSAID) toxicity—
due to hematemesis and melena.
• Calcium—hypercalcemia (total serum 
calcium >12.5 mg/dL, ionized calcium >6.0 
mg/dL). Hypercalcemia is immediate (2–3 
hours) and transient (will decline to normal 
within 24 hours post ingestion) with calcipo -
triol ingestion. In cholecalciferol rodenticide 
toxicity, hypercalcemia is evident 12 hours post 
ingestion and persists for weeks if not treated.
• Hyperphosphatemia (>8 mg/dL) may 
precede hypercalcemia.
• Hyposthenuria, proteinuria, and glucosuria.
• In acute, one‐time ingestions, serum 25‐
hydroxy vitamin D concentration is increased 
at least 10 times normal (normal ranges: dogs, 
60–215 nmol/L; cats, 65–170 nmol/L) in 
cholecalciferol toxicosis.
• In chronic intoxications, serum 25‐hydroxy 
vitamin D concentrations can increase from 
1.5 to 5 times above normal values.
• Serum 1,25-dihydroxy vitamin D is only 
transiently increased and is of limited 
diagnostic value.
• The total calcium‐to‐total phosphorus ratio 
in renal cortex of deceased dogs is in the 
range of 0.4–0.9 (normal <0.3) for all vitamin 
D‐related intoxications.
• Renal cortical 25‐hydroxy vitamin D 
concentration >80 nmol/L supports a 
diagnosis of cholecalciferol toxicosis.
• Biliary 25‐hydroxy vitamin D concentra-
tion >100 nmol/L supports a diagnosis of 
• Decreased intact parathyroid hormone 
(iPTH) (normal in dogs is 3–17 pmol/L and 
for cats is 0–4 pmol/L).
• Normal Na/K ratio.
IMAGING
Ultrasonography—renal, gastric wall, lung 
hyperechogenicity.
• Electrocardiogram—may show bradycardia, 
sinus tachycardia, ventricular premature 
• Endoscopy—may reveal erosive/hemor-
rhagic gastric mucosa.
• Diffuse mineralization of gastric wall and 
intestines; hemorrhage in gastric mucosa; 
mineralization of the soft palate, salivary 
glands, other soft tissues.

1210  Blackwell’s Five-Minute Veterinary Consult  
R• Necrosis and mineralization of myocardium 
(especially the atria) and large blood vessels; 
myocardial degeneration.
• Mineralization of glomerular mesangium 
and capsule, and renal tubular basement 
• T ubular necrosis.
• Mineralization of lungs.
  TREATMENT
• Cholecalciferol—once clinical signs show 
(usually 24–36 hours post ingestion), gastric 
decontamination is not worth while.
• Hospitalization with close observation in all 
cases for at least 48 hours post ingestion.
• Correct dehydration and electrolyte 
imbalances (hypokalemia).
• Enhance calciuresis with fluid therapy—
strongly recommended for all patients.
• Peritoneal dialysis with a calcium‐free 
dialysate—for severe azotemia and hyper- 
calcemia.
• Blood transfusion—if anemia is severe or in 
case of hypovolemia.
• Antibiotic therapy—as needed.
• Parenteral alimentation—recommended to 
rest the gut and to overcome anorexia.
DIET
Offer low‐calcium, low‐phosphorus diets.
• Caution client to keep all rodenticide 
products in places that are inaccessible to pets.
• Warn client that vitamin D toxicity is a 
severe and costly disease to treat with 
prolonged therapy and hospitalization.
• Pamidronate disodium—to treat hyper- 
calcemia.
• Salmon calcitonin—to treat hypercalcemia.
Decontamination of Gastrointestinal 
Tract
• Within 2 hours of vitamin D ingestion.
• Emetic and activated charcoal followed by 
osmotic cathartics.
• Dogs—apomorphine 0.02–0.04 mg/kg IV, 
IM, SC, or subconjunctivally.
• Cats—xylazine 0.4–0.5 mg/kg IV.
• Activated charcoal powder (1–4 g/kg) 
combined with a saline cathartic (magnesium 
or sodium sulfate, 250 mg/kg)—PO or by 
gastric tube.Hypercalcemia Reduction
• Pamidronate disodium 1.3–2.0 mg/kg in 
0.9% sodium chloride slow IV over 2–4 
hours; repeat once in 3–4 days for large 
ingestions; do not combine with salmon 
calcitonin.
• Salmon calcitonin 4–6 IU IM or SC every 
6 hours till calcium concentration stabilizes; 
rarely used as limited efficacy and patients 
may become refractory.
• IV fluids: 0.9% sodium chloride or 5% 
dextrose with 0.45% sodium chloride fluids 
to begin; change as needed.
• Prednisolone—dogs and cats: 2–6 mg/kg 
IM or PO q12h.
• Furosemide—dogs, 2–6 mg/kg; cats, 1–4 
mg/kg SC, IV, or IM q8–12h.
• Diazepam 0.5–1 mg/kg IV, repeat as 
Control of Clinically Significant 
Ventricular Arrhythmias
• Lidocaine—dogs, 2–4 mg/kg IV over 1 
minute, repeat up to 8 mg/kg; cats, use 
cautiously at 0.25–0.5 mg/kg IV slowly.
Gastrointestinal Protection
• Sucralfate 0.25–1 g PO q6–8h.
• Famotidine 0.5–1 mg/kg IV, IM, PO q12h.
• Maropitant 1 mg/kg SQ, IV or PO q24h.
• Supratherapeutic doses of pamidronate 
disodium may worsen renal failure.
• Salmon calcitonin—associated with side 
effects: anorexia, anaphylaxis, and emesis. 
Rarely used.
• Xylazine—may aggravate respiratory 
depression and result in vagal‐mediated 
slowing of the heart rate.
• Prolonged prednisolone therapy may result 
in adrenocortical suppression; taper doses 
gradually over a 2‐ to 4‐week treatment 
period.
  FOLLOW‐UP
• Following pamidronate therapy—serum 
calcium and BUN at 24, 48, and 72 hours 
following exposure; if hypercalcemia still 
present, repeat pamidronate infusion 72 or 96 
hours after the first infusion and monitor 
serum calcium and BUN q48h.
• Following calcitonin therapy—serum 
calcium and BUN; monitor q24h and 
continue adjusting dose until calcium returns 
to normal (24–48 hours for calcipotriol, or 
2–4 weeks for cholecalciferol).• Cholecalciferol‐induced hypercalcemia is 
persistent, requiring long‐term management 
and supportive care (2–4 weeks).
Keep rodenticides out of reach of pets.
• Chronic renal failure—inability to 
concentrate urine.
• Subclinical renal, cardiovascular, and 
gastrointestinal sequelae—due to minerali- 
zation.
Cholecalciferol—depends on severity and 
duration of hypercalcemia; if hypercalcemia is 
unresponsive or severe mineralization occurs 
before therapy is initiated, prognosis is poor.
Distinguish from normal juvenile hypercalcemia.
Vitamin D has antiproliferative effects and 
the potential for teratogenesis.
SYNONYMS
N/A
• iPTH = intact parathyroid hormone.
drug.
Bates N. Vitamin D toxicosis. Compan Anim 
2017, 22(12):700–706.
48(6):1027–1038.
Peterson ME, Fluegenman K. Cholecalciferol. 
Top Compan Anim Med 2013, 28(1): 
24–27.
Rumbeiha WK. Cholecalciferol. In: Peterson 
Saunders, 2013, pp. 489–498.
Rumbeiha WK, Braselton WE, Nachreiner R, 
et al. The post‐mortem diagnosis of 
cholecalciferol toxicosis: A novel approach 
and differentiation from ethylene glycol 
toxicosis. J Vet Diagn Invest 2000, 
12:426–432.
Rumbeiha WK, Fitzgerald SD, Kruger JM, 
et al. Use of pamidronate disodium to 
reduce cholecalciferol‐induced toxicosis in 
dogs. Am J Vet Res 2000, 61:9–13.
Author  Wilson K. Rumbeiha
Consulting Editor  Lynn R. HovdaRodenticide Toxicosis—Cholecalciferol  (continued)

Canine and Feline, Seventh Edition  1211
RRodenticide Toxicosis—Phosphides
  BASICS
OVERVIEW
• Used as a rodenticide since the early 1930s 
at various concentrations (2–10%) in a 
powder, pellet, or paste formulation. Available 
as zinc, aluminum, and magnesium salts. 
• Distinctive odor, often described as 
acetylene, rotten fish, or garlic. • Most 
common route of exposure is ingestion; 
however, toxicosis can occur via inhalation 
and absorption through broken skin. 
• Hydrolysis leads to phosphine gas 
production. Phosphine gas has corrosive and 
irritant effects on the gastrointestinal (GI) 
mucosa, which leads to vomiting, hematemesis, 
or melena. The gas is rapidly absorbed and 
systemically distributed leading to effects on 
other organ systems. • Phosphine leads to the 
production of free radicals and oxidative 
stress, causing direct cellular damage and may 
inhibit cellular respiration. • Toxic exposure 
is reported to be 20–40 mg/kg; however, the 
gastric pH is reported to affect toxicity.
No known age, breed, or sex predilection.
SIGNS
• Within 15 minutes to 4 hours but can be 
delayed up to 18 hours. • GI—anorexia, 
vomiting, and melena. • Cardiovascular—
direct myocardial damage, arrhythmias, 
decreased inotropy, hypotension.  
• Respiratory—pulmonary edema, pleural 
effusion.  • Hemic/lymphatic/immune—
methemoglobinemia, Heinz body production. 
• Nervous—ataxia, weakness, tremors, 
hyperesthesia, and seizures. • Renal/urologic—
azotemia, acute renal failure. • Hepatobiliary—
increased alanine transaminase (ALT), aspartate 
transferase (AST), and total bilirubin. 
• Endocrine/metabolic—metabolic acidosis, 
electrolyte imbalance. • Musculoskeletal—
weakness, ataxia.
• Increased hydrolysis in a moist, acidic 
environment; thus, recent food ingestion lowers 
gastric pH and increases hydrolysis. Owner 
should be instructed not to feed their pet. 
• Owners and veterinary staff are at risk for 
inhalation exposure if the animal vomits in a 
poorly ventilated area. Owners should be told 
to lower their windows on the way to the clinic.
  DIAGNOSIS
• Organophosphate. • Metaldehyde. 
• Serotonin syndrome. • Nonsteroidal 
anti-inflammatory drug (NSAID) toxicosis. • T remorgenic mycotoxins. • Acute GI 
disease (hemorrhagic gastroenteritis [HGE], 
gastroenteritis, parvovirus). • Congestive 
heart failure. • Respiratory disease 
(noncardiogenic pulmonary edema—
secondary to electrocution, near drowning, 
seizures, or acute respiratory distress 
syndrome [ARDS]). • Metabolic disease 
(renal, hepatic, pancreatitis).
• May see increased liver enzymes (ALT, AST, 
and total bilirubin); can be delayed 3–5 days. 
• Electrolyte alterations (decreased potassium 
or magnesium).  • Methemoglobinemia, 
Heinz body formation, and subsequent 
• Confirmation through gas chromatography 
or a Dräger detection tube (referral laboratory 
testing). • Post-mortem samples from the 
liver, kidney.
IMAGING
If respiratory signs, thoracic radiographs to 
assess for pulmonary edema.
Are nonspecific.
  TREATMENT
• No antidote. • The goal of treatment with 
recent, asymptomatic patients is to safely 
decontaminate. • Administration of a liquid 
antacid such as magnesium hydroxide, 
aluminum hydroxide, calcium carbonate, or 
even a 5% sodium bicarbonate solution may 
help to increase the gastric pH and thus 
decrease phosphine gas production. • Emesis 
induction with apomorphine, hydrogen 
peroxide, or gastric lavage for gastric 
emptying. • Activated charcoal may help 
decrease toxicity but should be given only if 
the patient’s clinical status allows. • IV fluid 
therapy with monitoring for any clinical signs 
or progression of signs for at least 18 hours. 
• Supplemental oxygen for hypoxemia.
• GI protectants—famotidine 0.5–1 mg/kg 
IV/PO q12–24h, omeprazole 0.5–1 mg/kg 
PO q12–24h, sucralfate 0.25–1 g PO 
q8–12h, or possibly misoprostol 2–5  μg/kg 
PO q8h. • T remors—methocarbamol 
44–220 mg/kg IV or to effect; do not exceed 
330 mg/kg/day. • Seizures—diazepam 
0.5–1 mg/kg IV, phenobarbital 4–16 mg/kg 
IV to effect, levetiracetam 30–60 mg/kg IV, 
or propofol 1–8 mg/kg or to effect, followed 
by a CRI at 0.1–0.6 mg/kg/h. • Liver effects—
hepatoprotectants ( S-adenosylmethionine 18 mg/kg PO q24h, silymarin/milk thistle 
50–250 mg/day PO q24h. If associated 
coagulopathy—vitamin K1 2–3 mg/kg PO 
q12–24h. • Oxidative damage or for 
methemoglobinemia— N-acetylcysteine. 
• Painful—opioids (hydromorphone 
0.05–0.1 mg/kg IV) or tramadol 2–4 mg/kg 
PO q8–12h. Avoid NSAIDs.
  FOLLOW-UP
Varies on a case basis.
Several organ systems may be affected; vitals, 
heart rhythm, blood pressure, and CNS 
should be monitored for 18 hours.
Have owners remove all baits from 
Liver or renal failure.
• Asymptomatic patients should be 
monitored for up to 12–18 hours. 
• Symptomatic patients should be monitored 
for at least 48 hours or until life-threatening 
signs have resolved.
• ALT = alanine transaminase. 
• ARDS = acute respiratory distress syndrome. 
• AST = aspartate transferase.  
• GI = gastrointestinal.  • HGE = hemorrhagic 
gastroenteritis. • NSAID = nonsteroidal 
https://www.avma.org/KB/Resources/
Reference/Pages/Phosphine-product-
precautions.aspx
Gray SL, Lee JA, Hovda LR, et al. Potential 
zinc phosphide rodenticide toxicosis in 
dogs: 362 cases (2004–2009). J Am Vet 
Med Assoc 2011, 239:646–651.
Knight MW. Zinc phosphide. In: Peterson 
Saunders, 2013, pp. 853–864.
Author  Sarah L. Gray

1212  Blackwell’s Five-Minute Veterinary Consult  
RRoundworms (Ascariasis)
 BASICS
OVERVIEW
• Ascariasis caused by Toxocara canis  (dogs), 
T. cati  (cats), and Toxascaris leonina  (dogs, 
cats); Baylisascaris  (raccoons) can infect dogs 
and causes neural larval migrans in people. 
• T ransplacental transmission of T. canis  
larvae from bitch to pups causes prenatal 
infection; transmammary transmission of 
larvae occurs with both Toxocara  spp.; no 
transplacental or transmammary transmission 
with Toxascaris . • In first month of life, 
infected neonatal pups may develop 
abdominal pain and rapidly deteriorate before 
Toxocara  eggs appear in feces. • Older pups 
and kittens can acquire by ingesting eggs 
spread by dams with postgestational 
infection; dams can be infected by ingesting 
immature worm stages in pups’ feces or 
vomitus or by predation on vertebrate 
transport hosts. • Adult ascarids occur in 
lumen of small intestine; larval stages of 
Toxocara  spp. may migrate in liver and lungs. 
• If numerous, ascarids (up to 10–12 cm 
long) can distend intestine and cause colic, 
interference with gut motility, inability to 
utilize food, intestinal rupture.
• Dog and cat. • Important in puppies/kittens 
due to in utero /transmammary transmission.
SIGNS
• Abdominal distension; often with palpable 
intestinal distension. • Colic. • Weakness, loss 
of condition, cachexia; poor nursing or 
appetite; scant feces. • Coughing due to larval 
lung migration. • Entire litter may be affected.
• Dormant Toxocara  larvae in dam’s tissues is 
infection reservoir for puppies during 
gestation; queen becomes infected during late 
pregnancy or lactation and transfers to kittens 
via transmammary route. • Access to infected 
transport hosts. • Concurrent enteric 
infections. • Toxocara  larvae undergo extensive 
migration and can cause granulomatous 
inflammation (visceral larva migrans). Visceral 
larva migrans caused by ascarids is cause of 
human morbidity.  • Somatically arrested 
larvae in small vertebrates are source of 
infection for dogs/cats that hunt.
  DIAGNOSIS
• T ransmammary perinatal infection of 
neonates with hookworms (anemia, melena, weakness, lethargy, pallor, enteritis) or 
Strongyloides  (diarrhea); coccidiosis, giardiasis; 
examine feces for eggs or larvae. 
• Physaloptera .
N/A
IMAGING
N/A
• Fecal flotation to detect eggs: ◦ Toxocara  
eggs spherical pitted outer shell membrane, 
single dark cell filling interior, 80–85  μm 
(T. canis ), ~75 μm (T. cati ). ◦ Baylisascaris  
eggs similar to T. canis  eggs but smaller 
(~76 × 60  μm), more finely pitted shell. 
◦ Toxascaris  eggs ovoid, smooth exterior shell 
membrane, 1–2 cells with light-colored 
cytoplasm; cells do not fill interior of egg; 
80 × 70  μm in diameter. • Necropsy of 
siblings—identify ascarids by size, appearance. 
• Fecal ELISA—commercial test detects 
antigen produced by adult and immature 
roundworms of both sexes; can detect 
prepatent infection.
  TREATMENT
• Generally outpatient. • Acute severe cases 
treated as inpatients; provide parenteral fluids. 
• Alert client to possibility of sudden death or 
chronic debilitation. • T reat dam with 
adulticide/larvicide anthelmintic to remove 
intestinal stages and limit transmission to 
subsequent litters.
• Fenbendazole 50 mg/kg PO q24h for 
3 days. • Milbemycin oxime 0.5 mg/kg 
(dogs) or 2 mg/kg (cats) PO q30 days. 
• Moxidectin (dogs) 2.5 mg/kg, topically, 
q30 days. • Moxidectin (in combination 
with imidacloprid) 10 mg/kg, topically, q30 
days. • Emodepside 3 mg/kg, or praziquantel 
12 mg/kg, topically once for cats ≥8 weeks 
old; repeat in 30 days if cat is reinfected.
Adulticide Anthelmintics
• Pyrantel pamoate 5 mg/kg PO (dogs) or 
10–20 mg/kg PO (cats, extra-label).  
• Pyrantel/praziquantel, label dose for cats.  
• Febantel/praziquantel/pyrantel, label dose 
for dogs. • Ivermectin/pyrantel, label dose for dogs. • Selamectin 6 mg/kg, topically, once 
(T. cati,  cats): dogs, extra-label.
N/A
  FOLLOW-UP
Repeat post-treatment fecal exams on 
puppies/kittens and/or repeat anthelmintic 
treatment every 2–3 weeks until old enough 
for monthly anthelmintic product.
• Minimize environmental contamination, 
treat infected dogs/cats with anthelmintic, 
dispose of feces promptly. • Prevent dogs/cats 
from hunting or ingesting transport hosts. 
• Extra-label treatment of dam with adulticide/  
larvicide anthelmintic to remove intestinal 
stages and decrease vertical transmission.
T ransplacental transmission of large numbers 
of larvae can result in fetal death or birth of 
weak, nonviable offspring.
Prognosis good after anthelmintic treatment; 
guarded with severe prenatal T. canis  infection.
Greater concern in neonates.
• Visceral larva migrans, ocular larva migrans, 
neural larva migrans, chronic abdominal or 
cutaneous problems may follow ingestion of 
infective Toxocara  spp. or Baylisascaris  eggs by 
humans; advise clients to practice good 
hygiene after handling feces. • Most likely 
cause of neural larva migrans is Baylisascaris ; 
virtually all raccoons become infected with 
Baylisascaris  and therefore extreme caution 
should be exercised with clients having 
raccoons as “pets.”
• http://www.capcvet.org • http://www.cdc.gov
Saunders, 2009, pp. 197–198, 201–208.

Canine and Feline, Seventh Edition  1213
SSago Palm Toxicosis
  BASICS
OVERVIEW
• Cycad palms, also called sago palms, belong 
in the family Cycadaceae. • Native to tropical 
and subtropical regions but have become 
popular ornamental plants in the United 
States. • Cycas revoluta , Cycas circinalis,  and 
Zamia floridana  are the most common species. 
• Contain the toxins cycasin, betamethylamino- l-
alanine, and an unidentified high-molecular-
weight compound. • Toxins present in all parts 
of the plant; highest concentrations in seeds. 
• Cycasin is metabolized by the intestinal flora 
to the active hepatotoxic, carcinogenic, 
mutagenic, teratogenic, and neurotoxic 
compound methylazoxymethanol (MAM). 
• Cycad toxicosis has been documented in 
several animal species (dogs and ruminants) 
and humans. • In dogs, gastrointestinal (GI) 
disturbances and hepatic damage predominate; 
nervous system involvement is less common.
SIGNS
• GI disturbances such as vomiting, diarrhea, 
and abdominal pain. • Signs associated with 
hepatic damage (ecchymoses, petechiae, 
hemorrhage, edema, etc.). • Gait 
abnormalities; paresis/paralysis; tremors. 
• Depression, coma, and death.
Access to and ingestion of cycad palm.
  DIAGNOSIS
Other Causes of Acute GI Upset
• Infectious. • Metabolic. • Toxic. • Dietary.
Other Causes of Acute Liver Failure
• Microcystins (hepatotoxic blue-green algal 
toxins)—access to water with algal bloom, 
algal material on legs or in stomach contents, 
detection of microcystins in stomach contents. 
• Amanitin—access to mushrooms ( Amanita , 
Galerina , and Lepiota  spp.), GI signs between 
6 and 24 hours after ingestion. • Cocklebur 
(Xanthium  spp.)—access to cocklebur (only 
seeds and two-leaf cotyledon stage are toxic). 
• Aflatoxins—access to moldy food. 
• Acetaminophen overdose. • Xylitol—access 
to xylitol-containing products (sugar-free 
gum, chewable vitamins, baked goods); initial 
hypoglycemia. • Severe acute pancreatitis.CBC/BIOCHEMISTRY/URINALYSIS
• Anemia. • Elevated serum liver enzymes 
(alanine transaminase, aspartate transaminase, 
alkaline phosphatase, bilirubin). 
• Hypoalbuminemia. • Hypoglycemia. 
• Glucosuria, hemoglobinuria, myoglobinuria, 
bilirubinuria, proteinuria, and increased urine 
specific gravity.
• Ammonia tolerance test—hyperammonemia. 
• Prolonged prothrombin time/partial 
thromboplastin time.
IMAGING
N/A
• History of cycad palm ingestion and presence 
of appropriate clinical signs. • Identification of 
plant in ingesta or feces. • Biopsy and histo -
pathology of liver—hepatic necrosis. 
• Necropsy—hepatic centrilobular necrosis.
• Detection of cycad palm material in GI 
tract and/or in feces. • Gross detection of 
liver enlargement. • Histologic detection of 
centrilobular and midzonal coagulative 
hepatocellular necrosis.
  TREATMENT
• No antidote available. • GI decontamination 
with activated charcoal can be attempted but 
efficacy is unknown. • Supportive care 
including close monitoring and, depending on 
the severity of clinical signs, IV fluids, correction 
of electrolyte imbalances and hypoglycemia, 
vitamin K1, and plasma transfusions.
• Activated charcoal—multi-dose activated 
charcoal at 1–4 g/kg PO q4–6h for 2–3 days 
post ingestion. Mix activated charcoal in water 
at 1 g/5−10 mL of water. • IV fluids—
1 mL/kg IV slow bolus (1–3 minutes). 
• Vitamin K1—0.5–1.5 mg/kg SC or IM 
q12h; 1 mg/kg PO q24h. • Blood products—
dependent on hemostatic test results.
• S-Adenosylmethionine—antioxidant and 
hepatoprotectant; no data on efficacy in sago 
palm toxicosis available. Dose 20 mg/kg PO 
q24h. • Ascorbic acid and cimetidine—
hepatocyte protectors; no data on efficacy in sago palm toxicosis available. Can be given 
for supportive therapy. • N-Acetylcysteine—
antioxidant; no data on efficacy in sago palm 
toxicosis available. A glutathione precursor 
that can be included in the treatment regimen 
for acute fulminant hepatic failure at 140 mg/
kg IV load, followed by 70 mg/kg IV q6h for 
7 treatments.
N/A
  FOLLOW-UP
• Liver enzymes/function. • Coagulation status.
Deny access to sago palms.
• Hepatic encephalopathy. • Disseminated 
intravascular coagulation. • Renal failure.
• Dogs develop vomiting within minutes, 
followed by further GI upset. • Changes in 
clinical laboratory values occur after 24–48 
hours. • Nadir serum albumin levels and 
nadir platelet counts are important prognostic 
indicators. • Liver failure within a few days. 
• Prognosis is poor to guarded.
• MAM = methylazoxymethanol.
sago-palm/ • http://www.aspca.org/pet-care/
animal-poison-control/toxic-and-non-toxic-
plants/fern-palm
Albretsen JC, Khan SA, Richardson JA. 
Cycad palm toxicosis in dogs: 60 cases 
(1987–1997). J Am Vet Med Assoc 1998, 
213(1):99–101.
Clarke C, Burney D. Cycad palm toxicosis in 
14 dogs from Texas. J Am Anim Hosp 
Assoc 2017, 53:159–166.
Ferguson D, Crowe M, McLaughlin L, et al. 
Survival and prognostic indicators for cycad 
intoxication in dogs. J Vet Intern Med 
2011, 25(4):831–837.
Authors  Adrienne C. Bautista and Birgit 
Puschner

1214  Blackwell’s Five-Minute Veterinary Consult  
SSalivary Mucocele
  BASICS
OVERVIEW
• Salivary mucoceles (sialoceles) are nonepithelial-  
lined cavities filled with saliva that has leaked 
from a damaged salivary gland or duct; they 
are surrounded by granulation tissue that 
forms secondary to inflammation caused by 
the free saliva.
• There are four major pairs of salivary 
glands: parotid, mandibular, sublingual, and 
zygomatic. Smaller salivary glands are located 
in the soft palate, lips, cheeks, and tongue.
• Types of mucoceles are listed in Table 1. 
The most common type occurs with injury to 
the sublingual gland or its duct.
• Three times more frequent in dogs than in 
cats.
• Commonly affected breeds include 
miniature poodle, German shepherd dog, 
dachshund, and Australian silky terrier.
• Slight predisposition of males compared to 
females.
• No age predisposition.
SIGNS
Cervical Sialocele
• Soft, fluctuant, minimally painful or 
nonpainful, gradually developing cervical 
mass.
• Pain is usually manifested only during the 
acute-manifestation phase of the sialocele.
Sublingual Sialocele
• Soft, sublingual swelling (also called ranula; 
from Latin: rana, frog).
• Often blood-tinged saliva secondary to 
self-trauma while eating.
• Abnormal tongue movement, tongue 
displaced, dysphagia.
Pharyngeal Sialocele
• Swelling in pharyngeal wall.
• Dysphagia and respiratory distress when 
very large.
Zygomatic Sialocele
• Periorbital swelling.
• Exophthalmos and protrusion of third 
eyelid.
• Divergent strabismus.
• Periocular pain.
• Pressure-related neuropathy of the optic 
nerve.
The cause is rarely identified. Suspected 
causes:
• Blunt trauma to the head and neck (choke 
chains).• Bite wound.
• Penetrating foreign body.
• Ear canal surgery, parotid duct 
transposition, maxillectomy.
• Sialoliths.
• Dirofilariasis.
  DIAGNOSIS
• Diagnosis is based on history, visual 
examination, and paracentesis of the fluid-  
filled swelling.
• Determine the site of origin with help of 
oral examination, palpation, sialography, or 
exploration of the sialocele.
• Sialoadenitis (second most common 
salivary gland disease; usually involving the 
zygomatic gland; often concurrent with 
sialoliths and other ductal foreign bodies).
• Sialadenosis (nonpainful, noninflammatory 
salivary gland swelling; usually mandibular 
gland).
• Necrotizing sialometaplasia (painful salivary 
gland swelling; squamous metaplasia with 
ischemic necrosis; usually mandibular gland).
• Salivary neoplasia (rare; mandibular and 
parotid glands most commonly involved; 
usually adenocarcinomas).
• Sialoliths (calcium phosphate or carbonate).
• Cervical abscess.
• Abscessed or neoplastic lymph nodes.
Laboratory abnormalities are rarely seen.
N/A
IMAGING
• Ideally CT or MRI with contrast.
• Skull and upper neck radiography only 
helpful to identify sialoliths, foreign bodies, 
• Sialography (injection of iodinated, 
water-soluble contrast agent into the salivary 
duct) reserved for patients with trauma, 
previous surgeries, or fistulous draining tracts 
and can be helpful to determine the size and 
source of sialoceles.
• Retrobulbar ultrasound.
Aseptic Paracentesis
• Differentiates sialoceles from neoplasia and 
abscess.
• Aspirated fluid is viscous, clear, or pink, 
yellow, brown or black (blood-tinged) with a 
low cell count; surrounding soft tissue may 
show low-grade chronic plasmacytic-
lymphocytic inflammation.• Cytologic evaluation (Wright’s stain) reveals 
diffuse or irregular clumps of pink to 
violet-staining mucin, large phagocytic cells 
with small, round nuclei and foamy 
cytoplasm, intermixed salivary gland 
epithelial cells, and nondegenerate 
neutrophils in small numbers.
• Stain with a mucus-specific stain (e.g., 
periodic acid–Schiff) for definitive  
  TREATMENT
• Patients with acute respiratory distress 
(pharyngeal sialoceles) might need to be 
intubated or have a temporary tracheostomy 
performed. T ransoral drainage via stab 
incision may be required prior to intubation.
• Complete surgical excision of the involved 
gland–duct complex and drainage of the 
sialocele is the treatment of choice. Permanent 
drainage may be achieved with marsupialization 
of sublingual and pharyngeal sialoceles.
Antibiotics based on bacteriologic evaluation, 
if concurrent abscessation or sialadenitis.
Nonsurgical treatment with repeated drainage 
or injection of cauterizing or anti-
inflammatory agents is not curative and will 
complicate subsequent surgery by causing 
abscessation or fibrosis.
  FOLLOW-UP
Penrose drains placed after sialadenectomy are 
usually removed 24–72 hours following 
surgery.
• Seroma formation (after excessive tissue 
dissection, insufficient dead space manage -
ment, and when Penrose drains are not used 
following sialadenectomy).
• Sialocele recurrence (<5% with complete 
resection).
PROGNOSIS
• Excellent prognosis with complete surgical 
excision.
• Seroma formation and infection complicate 
successful surgical excision.

Canine and Feline, Seventh Edition  1215
S  MISCELLANEOUS
Sialoadenitis (resected salivary glands often 
show various degrees of inflammation 
histologically).
SYNONYMS
• Salivary mucocele.
• Sialocele.
Gracis M, Reiter AM, Ordeix L. Management 
of selected non-periodontal inflammatory, infectious and reactive conditions. In: Reiter 
AM, Gracis M, ed., BSAVA Manual of 
Canine and Feline Dentistry and Oral 
Surgery, 4th ed. Gloucester, UK: BSAVA, 
2018, pp. 192–193.
Reiter AM. Commonly encountered dental 
and oral pathologies. In: Reiter AM, Gracis 
M, ed., BSAVA Manual of Canine and 
Feline Dentistry and Oral Surgery, 4th ed. 
Gloucester, UK: BSAVA, 2018, pp. 
113–114.
Reiter AM, Gracis M. Management of dental 
and oral trauma. In: Reiter AM, Gracis M, 
ed., BSAVA Manual of Canine and Feline 
Dentistry and Oral Surgery, 4th ed. Gloucester, UK: BSAVA, 2018, pp. 
220–222.
Ritter MJ, von Pfeil DJ, Stanley BJ, et al. 
Mandibular and sublingual sialocoeles in 
the dog: a retrospective evaluation of 41 
cases, using the ventral approach for 
treatment. N Z Vet J 2006, 54(6):333–337.
Susanne Lauer.Types of sialoceles.
Type Location Gland/duct involved
Cervical Intermandibular space, jaw angle, upper cervical region Sublingual or mandibular
Sublingual Sublingual tissue Sublingual or mandibular
Pharyngeal Pharyngeal wall Sublingual
Zygomatic Ventrolateral to the globe Zygomatic
Parotid mucocele Side of the face, jaw angle, ventral to ear ParotidTable 1(continued)  Salivary Mucocele

1216  Blackwell’s Five-Minute Veterinary Consult  
SSalmon Poisoning Disease
  BASICS
OVERVIEW
• Infection with rickettsial organism 
Neorickettsia helminthoeca , an obligate 
intracellular pathogen that resides within 
trematode (fluke) vector Nanophyetus salmincola .
• Organism invades small intestinal 
epithelium and associated lymphoid tissue 
after ingestion of uncooked or undercooked 
fluke-infected salmonid fish; animal develops 
acute systemic illness with high fever, gastro -
• Geographically restricted to coastal regions 
of northern California, Oregon, Washington, 
southern British Columbia due to the 
geographic distribution of the Oxytrema 
silicula , intermediate host for trematode.
• All ages; median 3 years old.
• Dogs of all breeds and sexes; intact male 
dogs and Labrador retrievers may be over  - 
represented.
SIGNS
• Fever (up to 107.6°F/42°C); terminal 
hypothermia may develop.
• Diarrhea, may contain melena or frank blood.
• Uncommonly, mental obtundation, cervical 
pain, twitching, seizures.
• Residence in endemic area.
• Ingestion of uncooked or undercooked fish 
containing fluke metacercariae that harbor N. 
helminthoeca ; salmonid fish (salmon and 
trout) most common; other freshwater fish 
can be infected.
• Any part of fish can be infected.
• Supermarket-bought fish have been 
implicated in some cases.
• Dogs from non-endemic areas can develop 
disease after ingesting transported fish.
• Infection also reported after swimming, 
without apparent fish ingestion.
  DIAGNOSIS
• Toxicosis.
• Canine parvovirus type 2 infection.
• Ehrlichia canis  infection.• Anaplasma phagocytophilum  infection.
• Canine distemper virus infection.
• Rocky Mountain spotted fever.
• Whipworm infestation.
• Disseminated cryptococcosis.
• Thrombocytopenia (90% of dogs), 
neutrophilia with a left shift, lymphopenia.
• Serum chemistry nonspecific—electrolyte 
abnormalities, hypoproteinemia, increased 
activity of alkaline phosphatase, hypo- 
cholesterolemia.
• Urinalysis—proteinuria, bilirubinuria.
Some dogs have laboratory findings suggestive 
of disseminated intravascular coagulation.
IMAGING
Abdominal ultrasound—splenomegaly with 
mottled echotexture, abdominal lymphadeno -
megaly; fluid-distended intestinal loops with 
wall thickening, corrugation, hypermotility 
or hypomotility.
• Lymph node aspirates—increased numbers 
of histiocytes containing basophilic granular 
material in cytoplasm (rickettsial inclusions).
• Fecal examination—operculated eggs of 
trematode N. salmincola ; using combination of 
centrifugal fecal flotation and fecal sedimentation 
maximizes sensitivity of test (sensitivity 93%).
• Where available, PCR assays for N. 
helminthoeca  can be performed on lymph 
node aspirates or feces.
• Lymphoid tissue enlargement—tissues 
yellowish with prominent white foci.
• Gastrointestinal tract thickening with white 
nodules.
• Intestinal contents—frequently contain free 
blood; flukes may not be grossly visible.
• Histopathology—depletion of lymph node 
follicles; infiltration of lymphoid tissues and 
intestinal submucosa by histiocytes; 
cytoplasm contains numerous lymphoid 
follicles; flukes may be found embedded in 
gastrointestinal mucosa.
  TREATMENT
• Inpatient—acutely ill patients.
• Supportive therapy—IV fluids with 
electrolytes; colloids or packed red blood cell 
transfusions may be needed; consider 
antiemetics and parenteral nutrition.  MEDICATIONS
• Oxytetracycline 7.5–10 mg/kg IV q12h for 
7–14 days.
• Doxycycline 5 mg/kg PO, IV q12h for 
7–14 days.
• Praziquantel 10–30 mg/kg PO q24h for 
1–2 days to kill flukes.
  FOLLOW-UP
Monitor hydration, electrolytes, acid–base 
balance, body temperature.
• Avoid feeding/eating improperly cooked fish.
• Inform client of necessity to act quickly; 
consider other dogs that may have eaten same 
raw fish.
• Animals succumb within 5–10 days of 
infection unless treated.
• With early diagnosis and treatment—
prognosis excellent. Animals without severe 
gastrointestinal signs show rapid clinical 
response to oral doxycycline (within 24–48 
hours); dogs with severe gastrointestinal signs 
may require hospitalization and aggressive 
treatment for >1 week.
• Untreated—often fatal.
Infection with N. salmincola  does not itself 
cause severe clinical disease.
N. salmincola  can cause gastrointestinal 
disturbances and eosinophilia in humans; 
N. helminthoeca  does not cause human 
disease.
https://www.vetmed.wsu.edu/outreach/
Pet-Health-Topics/categories/diseases/
salmon-poisoning
Sykes JE. Salmon poisoning disease. In: Sykes 
2014, pp. 311–319.

Canine and Feline, Seventh Edition  1217
SSalmonellosis
  BASICS
Infection caused by many different serotypes 
of Salmonella , causing enteritis, septicemia, 
and abortions.
• Salmonella —Gram-negative bacterium; 
colonizes small intestine (ileum); adheres to 
and invades enterocytes; enters and multiplies 
in lamina propria and local mesenteric lymph 
nodes; cytotoxin and enterotoxin are produced; 
inflammation and prostaglandin synthesis 
ensue; results in secretory diarrhea, mucosal 
sloughing.
• Uncomplicated gastroenteritis—organisms 
are stopped at the mesenteric lymph node 
stage; patient has only diarrhea, vomiting, 
• Bacteremia and septicemia following 
gastroenteritis—more serious; focal extra -
intestinal infections (abortion, joint disease) 
or endotoxemia may result; may cause 
thrombosis, disseminated intravascular 
coagulation (DIC), death.
• Some patients recover from septicemia but 
have prolonged recovery.
• Gastrointestinal—enterocolitis; inflammation, 
mucosal sloughing, secretory diarrhea.
• Systemic disease (e.g., bacteremia, focal 
infections, septicemia)—multiorgan infarction, 
thrombosis, abscesses, meningitis, osteomyeli-
tis, abortion.
GENETICS
N/A
• T rue incidence unknown; prevalence in 
healthy dogs/cats similar to diarrheic 
animals.
• Dogs—clinical disease most often seen 
in the young and pregnant bitches. Common 
in racing greyhounds and sled dogs due to 
raw meat diets; presence of Salmonella  in feces 
does not necessarily imply infection.
• Cats—natural resistance; stressed, hospital -
ized, and shelter cats at risk. Pandemics of 
salmonellosis in migrating songbirds (usually 
Salmonella  Typhimurium) in spring lead to 
epidemics in bird-hunting cats.
• Raw meat diet (especially chicken) 
risks— Campylobacter  spp. in addition to 
Salmonella  spp. and Listeria spp . Outbreaks 
linked to pet foods/treats common.
Worldwide
Species
Dog and cat.Mean Age and Range
• Dogs—neonatal/immature puppies, 
pregnant bitches. Most adult carrier dogs 
• Cats—adults highly resistant unless 
treated with an antimicrobial prior to 
exposure.
SIGNS
Disease severity—subclinical (carrier state, 
more common) to severe clinical cases in 
neonatal and stressed adult animals.
• Diarrhea, can be hemorrhagic.
• Fever.
• Malaise.
• Vaginal discharge/abortion—dogs.
• Chronic febrile illness—persistent fever, 
anorexia, malaise without diarrhea.
• Asymptomatic carrier states—no clinical 
signs.
• Gastroenteritis—fever (102–104°F/39–
40°C), diarrhea with mucus and/or blood, 
dehydration, abdominal pain, tenesmus, pale 
mucous membranes, weight loss.
• Gastroenteritis with bacteremia, septic 
shock, or endotoxemia—brick-red mucous 
membranes, tachycardia, bounding pulses, 
rapid capillary refill time (unless 
decompensatory shock), tachypnea, 
abdominal pain, weakness.
• Focal extraintestinal infections—conjunctivitis, 
cellulitis, pyothorax, diskospondylitis.
• Cats—chronic febrile illness, vague, 
nonspecific clinical signs.
• Recovering patients—chronic intermittent 
diarrhea for 3–4 weeks (may shed Salmonella  
in stool >6 weeks).
CAUSES
• Any one of more than 2,000 serotypes of 
salmonellae.
• T wo or more simultaneous serotypes in host 
animal can occur:
 ◦Most common serotypes—Newport, 
Typhimurium, Albany, 4,5,12:i:, Dublin, 
Heidelberg.
Disease Agent
• Salmonella  serotype determines virulence, 
infectious dose, and route of exposure.
• Host factors that increase susceptibility:
 ◦Age—neonatal/young dogs and cats; 
immature immune system.
 ◦Health—debilitated young animals 
(immature gastrointestinal tract, poorly 
developed normal microbial flora) or adults 
with concurrent disease.
 ◦Disrupted gastrointestinal flora (adult 
cats)—antimicrobial treatment; exposure to 
salmonellae during hospitalization.Environmental Factors
• Diet:
 ◦Raw food diet is major risk factor.
 ◦Contaminated dog treats (e.g., pig ears).
 ◦Dehydrated (dry) pet food; semi-moist 
foods usually not as risky.
• Coprophagia.
• Grooming habits—can contaminate 
environment, feed and water dishes.
• Dense population—colonies, boarding 
facilities, shelters:
 ◦Build up of Salmonella  in environment, 
more efficient fecal–oral cycling.
 ◦Stress.
 ◦Exposure to infected (or carrier) animals.
• Unsanitary environment.
Hospitalized Animals
Nosocomial exposure (plus stress) or activation 
(by stress) of preexisting asymptomatic (carrier) 
Salmonella  infection, especially in animals 
treated with antimicrobial drugs.
Vaccinated Cats
Death reported in kittens (likely to be 
subclinically infected by Salmonella ) post 
vaccination, with high titers of modified live 
panleukopenia vaccine.
  DIAGNOSIS
• Acute gastroenteritis—infectious, foreign 
body, neoplasia:
 ◦Viral gastroenteritis—canine enteric 
coronavirus, canine parvovirus, rotavirus, 
canine distemper.
 ◦Bacterial gastroenteritis— Escherichia coli , 
Campylobacter jejuni , Yersinia enterocolitica .
• Bacterial overgrowth syndrome—
Clostridium difficile, C. perfringens.
• Parasites—helminths, protozoa (Giardia, 
Coccidia, Cryptosporidia), salmon poisoning.
• Acute gastritis—erosions or ulcers.
• Diet-related—allergy or food intolerance.
• Drug- or toxin-induced distress.
• Extraintestinal disorders (metabolic 
disease).
• CBC—variable; depends on stage of illness: 
initially neutropenia, left-shifted neutrophils, 
lymphopenia, thrombocytopenia, 
non-regenerative anemia.
• Hypoalbuminemia, electrolyte abnormali-
ties related to gastrointestinal losses.
• Fecal/rectal bacterial culture—special media 
needed:
 ◦Subclinical carriers may have intermittent 
positive fecal culture (>6 weeks).
 ◦Use of antimicrobials before sampling 
may yield false-negative culture.
 ◦Serotyping of cultured organisms—
helpful to define outbreak.

1218  Blackwell’s Five-Minute Veterinary Consult  
S• Cultures of blood and joint fluid, ileum, 
mesenteric lymph node, liver/spleen, bone 
marrow.
• Fecal cytology—leukocytes present.
• Fecal Salmonella  PCR.
• Abdominal ultrasound (clinical gastroen-
teritis)—lymphadenomegaly, enterocolitis, 
typhlitis, peritonitis.
Lymphoplasmacytic, neutrophilic typhlitis/
enteritis with ulceration, crypt abscessation, 
lymphoid hyperplasia, pyogranulomas; 
  TREATMENT
• Outpatient—uncomplicated gastroenteritis.
• Inpatient—with bacteremia/septicemia, 
gastroenteritis in neonatal/immature animals 
(rapidly debilitated).
• Varies according to severity of illness—
assess dehydration, body weight, ongoing 
fluid loss, shock, hematocrit, albumin, 
electrolytes, acid–base status.
• Supportive care—fluid and electrolyte 
replacement:
 ◦Parenteral, balanced, polyionic isotonic 
replacement solution (lactated Ringer’s).
 ◦Oral fluids—hypertonic glucose 
solutions; for secretory diarrhea.
• Plasma transfusions—if serum albumin 
<2 g/dL.
ACTIVITY
• Isolate patients.
• Cage rest, provide warmth during illness.
DIET
Restrict food 24 hours in adults; gradually 
introduce highly digestible, low-fat diet.
Instruct client to wash hands frequently and 
to restrict access to patient in acute stages of 
disease; large numbers of salmonellae may be 
shed in stool.
Asymptomatic Carrier State
• Antimicrobials—contraindicated:
 ◦Quinolones—clear carrier states in 
humans; controlled trials in animals needed 
before this can be recommended.Uncomplicated Gastroenteritis
• Antimicrobials not indicated.
• Locally acting intestinal adsorbents and 
supportive therapy.
Neonates, Aged, and Debilitated 
Animals
• Antimicrobial therapy—indicated; culture 
and susceptibility testing with minimal 
inhibitory concentration recommended:
 ◦T rimethoprim-sulfa: 15 mg/kg PO, SC 
q12h.
 ◦Enrofloxacin: 5 mg/kg q24h (cat); 
10 mg/kg PO, IM, q24h (dog).
 ◦Chloramphenicol: dogs, 50 mg/kg PO, 
IV, IM, SC q8h; cats, 50 mg/kg total PO, 
IV, IM, SC q12h.
• Recent strains of Salmonella  are multidrug-
resistant; adjust empirical therapy based on 
antimicrobial susceptibility testing.
• Chloramphenicol, trimethoprim-sulfa—use 
cautiously in neonatal and pregnant patients.
• Fluoroquinolones—avoid use in pregnant, 
neonatal, or growing animals because of 
concern for adverse effects on cartilage; do 
not administer to cats at dosages higher than 
  FOLLOW-UP
• Fecal culture—repeat monthly for few 
months to assess development of carrier state.
• Other animals—monitor for secondary 
spread of infection.
• Advise client to contact veterinarian if 
patient shows signs of recurring disease.
• Keep animals healthy—proper nutrition; 
avoid raw meat diets; vaccinate for other 
infectious diseases; clean, disinfect cages, 
runs, and food/water dishes frequently; store 
food, feeding utensils properly.
• Reduce overcrowding.
• New arrivals—isolate and screen; monitor 
for sickness before mixing with other 
animals.
• Protect animals being treated with 
antimicrobial drugs from exposure to 
Salmonella -contaminated environment (e.g., 
animal hospital).
• Experimental live attenuated vaccine shows 
promise, especially for racing dogs.
• Spread of infection to other animals or 
humans within household.• Development of chronic infection with 
diarrhea.
• Recurrence of disease with stress.
• Uncomplicated gastroenteritis—prognosis 
excellent; frequently self-limited; patients 
recover with good nursing care.
• Recovered animals may shed Salmonella  
intermittently for months or longer.
• Neonatal, aged, pregnant, stressed animals—  
can develop sepsis or abortion; can be severe, 
debilitating; may lead to death if untreated.
Clinical disease is frequently seen in neonatal, 
or aged animals.
• High potential, especially in children, elderly, 
immunosuppressed, and antimicrobial drug 
users.
• Multidrug-resistant salmonellae have been 
reported.
• May complicate disease.
• Abortion—may be a sequela to infection.
• Antimicrobial therapy—consider the effect 
on the fetus.
disease.php?name=salmonella-nontyphoidal 
&lang=en
• https://www.cdc.gov/healthypets/index.html
Marks S, Rankin S, Byrne B, et al. 
Consulting Editor  Amie KoenigSalmonellosis  (continued)

Canine and Feline, Seventh Edition  1219
SSalt Toxicosis
  BASICS
• Salt ingestion results in direct irritation to 
the gastrointestinal mucosa, causing vomiting, 
diarrhea, and anorexia. Polydipsia is a 
common early sign that hypernatremia is 
developing.
• Hypernatremia (typically Na+ >170 mEq/L, 
dogs; >175 mEq/L, cats) may cause 
neurologic signs including lethargy, 
behavioral changes, ataxia, muscle tremors, 
and seizures. Coma and death may occur.
• LD50 (dogs) = 4 g NaCl/kg, <1 teaspoonful 
of table salt/kg body weight.
• Hypernatremia causes water movement 
from intracellular space to extracellular space 
(interstitium and blood vessel), resulting in 
cellular shrinkage/dehydration.
• In the brain, this may cause the parenchyma 
to pull away from the skull, causing intra­
cerebral and subarachnoid hemorrhage.
• In the lungs, fluid movement into the 
interstitial tissue may cause pulmonary 
edema.
• Idiogenic osmoles begin to develop intra  ­ 
cellularly within hours to prevent cellular 
dehydration but take 1–7 days for full 
compensation.
anorexia, polydipsia.
• Neuromuscular—twitching, muscle 
tremors, ataxia, seizures, coma.
• Pulmonary—edema, respiratory distress.
• Cardiovascular—hypervolemia, tachy  ­ 
cardia.
With ingestion, gastrointestinal signs and 
mild hypernatremia are common but 
neurologic signs occur in severe cases.
N/A
Species
Dogs and cats equally affected. There are no 
breed, age or sex predilections.
N/A
N/A
SIGNS
• Severity of signs is dependent on sodium level.
• Mild—lethargy, vomiting, diarrhea, polydipsia 
± polyuria.
• Severe—behavioral changes, twitching, 
muscle tremors, ataxia, seizures, coma, death.Historical Findings
• Ingestion of homemade playdough or clay.
• Administration of salt as an emetic.
• Exposure to other forms of salt (i.e., rock 
salt, baking soda).
• Swimming in the ocean/ingestion of 
saltwater.
• Abnormal hydration:
◦ Dehydration with vomiting and diarrhea.
◦ Overhydration and hypervolemia with 
saltwater ingestion or secondary to treat ­ 
ment.
• Ataxia, muscle weakness, muscle tremors.
CAUSES
• Salt intake:
◦ Salt ingestion—table salt, baking soda, 
salt for water softeners, deicing salt, ocean/
◦ Other products made with table salt—
homemade or commercial playdough, 
ornament dough.
◦ Iatrogenic with IV hypertonic saline or 
IV sodium bicarbonate; sodium phosphate 
enemas.
• Decreased water intake (typically chronic).
◦ Adipsia.
◦ No access to water.
• Free water loss:
◦ Mannitol bolus or CRI causes free water 
loss via kidneys.
◦ Activated charcoal with sorbitol (more 
common with multidose activated charcoal 
or high doses) causes free water loss via 
• Swimming in oceans and intake of saltwater.
• Outdoor pets with frozen or spilled water.
• Patients predisposed to dehydration—
kidney disease, unregulated diabetes mellitus, 
central diabetes insipidus, chronic vomiting 
and diarrhea, hyperthermia/fever.
  DIAGNOSIS
• Hypernatremic hyperosmolar nonketotic 
diabetes, chronic kidney disease, diabetes 
mellitus.
• Primary neurologic disease.
• Toxins that cause neurologic signs: 
(ethylene glycol, bromethalin, metaldehyde, 
baclofen, pyrethrins/pyrethroids, 
organophosphates/carbamates).
• Paintball ingestion
Biochemistry—hypernatremia, hyperchloremia, 
azotemia with dehydration, possible elevation 
of liver enzymes.OTHER LABORATORY TESTS
CSF sodium concentration can be measured. 
Normal is 135–150 mEq/L; >180 mEq/L is 
consistent with salt toxicosis.
IMAGING
• Thoracic radiography if respiratory signs to 
evaluate for hypervolemia and signs of fluid 
overload and pulmonary edema.
• MRI or CT—evaluate for subarachnoid or 
cerebral hemorrhage.
CSF tap for sodium concentration (rarely 
performed) and rule out other causes for 
• Hemorrhage of stomach, small intestine, 
and colon.
• Cerebral edema, perivascular hemorrhage 
and fibrinous exudate.
• Acute renal and hepatic necrosis.
  TREATMENT
Hospitalization recommended for electrolyte 
Asymptomatic
• Decontamination with emesis if appropriate 
time frame.
• Monitor Na level in the hospital for 6 hours 
post exposure.
• If asymptomatic and Na remains normal, 
discharge patient to be monitored at home.
Symptomatic
• Stabilize neurologic signs as needed.
• Decontamination with emesis if indicated.
• IV fluids for rehydration. May need to 
match fluid Na content to patient serum Na 
depending on chronicity and degree of 
• Calculate free water replacement for 
hypernatremia:
◦ IV use D5W or 0.45% NaCl + 2.5% 
dextrose; use with caution in patients with 
◦ Water oral or via nasoesophageal tube— 
use for stable patients that are not vomiting 
or those with underlying cardiac disease/
failure or evidence of fluid overload. Can be 
used with IV therapy.
◦ Acute toxicity (<24 hours)—lower Na 
acutely (over 1–2 hours) until neurologic 
signs resolve, then replace remaining free 
water over 6–24 hours.
◦ Chronic toxicity (>24 hours) or 
unknown time frame—lower Na slowly, 
not to exceed 12 mEq/day (0.5 mEq/h).

1220  Blackwell’s Five-Minute Veterinary Consult  
S• Free water deficit calculation:
[(patient Na ÷ normal Na) − 1] × (0.6 × body  
 weightkg) × 1000 = Free water deficit in  
 milliliters
DIET
Oral water can be offered to lower Na. Water 
intake should be regulated so that Na level 
does not drop too rapidly.
Outdoor pets may be susceptible to decreased 
intake with frozen or empty water containers 
or if they become trapped in a garage or shed. 
Heated water bowls and multiple water 
sources should be available.
Gastrotomy may be needed to remove 
homemade playdough or ornament dough if 
unable to remove with emesis or gastric lavage.
• Antiemetic for vomiting—maropitant 
1 mg/kg SC or IV q24h.
• Proton pump inhibitor if signs of stomach 
mucosal irritation:
◦ Pantoprazole 1 mg/kg IV slowly q24h.
◦ Omeprazole 1 mg/kg PO q24h.
• Methocarbamol 55–220 mg/kg IV slowly, 
to effect for muscle tremors; do not exceed 
330 mg/kg/day.
• Anticonvulsant such as diazepam 
0.5–2 mg/kg IV for seizures.• Furosemide 1–4 mg/kg IV q2–8h or a CRI 
0.1–0.5 mg/kg/h IV titrated to effect for 
hypervolemia or pulmonary edema until signs 
resolve.
Activated charcoal—will worsen hyper ­ 
natremia.
• Mannitol, hypertonic saline, and sodium 
bicarbonate should be used with caution as 
they may worsen hypernatremia.
• Diuretics such as furosemide may be helpful 
for Na excretion via the kidney but hydration 
status needs to be monitored carefully.
• Hyponatremia or rapid correction of 
chronic hypernatremia (due to idiogenic 
osmole formation) during treatment can cause 
cerebral edema formation and worsening or 
reoccurrence of neurologic signs.
N/A
  FOLLOW-UP
• Sodium level should be monitored during 
treatment; frequency depends on severity of 
signs and chronicity of hypernatremia but 
generally every 2–4 hours.
• Hydration status monitored every 4–6 hours.
Salt should not be recommended or given as 
an emetic.POSSIBLE COMPLICATIONS
Persistent neurologic impairment with severe 
toxicity.
• Neurologic signs should improve with 
improvement of Na level.
• Prognosis is generally good. Guarded to 
poor prognosis with severe neurologic signs 
and poor response to treatment.
N/A
SYNONYMS
Barr JM, Khan SA, Safdar A, et al. 
Hypernatremia secondary to homemade 
play dough ingestion in dogs: a review of 14 
cases from 1998–2001. J Vet Emerg Crit 
Care 2013, 14(3):196–202.
DiBartola SP . Disorders of sodium and water: 
hypernatremia and hyponatremia. In: Fluid, 
Electrolyte and Acid ­Base Disorders in 
Small Animal Practice, 4th ed. St. Louis, 
MO: Elsevier ­ Saunders, 2012, pp. 45–79.
Guillaumin J, DiBartola SP . Disorders of 
sodium and water homeostasis. Vet Clin 
Small Anim 2017, 47:293–312.
Consulting Editor  Lynn R. HovdaSalt Toxicosis  (continued)

Canine and Feline, Seventh Edition  1221
SSarcoptic Mange
  BASICS
OVERVIEW
A nonseasonal, intensely pruritic, highly 
contagious parasitic skin disease of dogs and 
other mammalian species caused by Sarcoptes 
scabiei  var. canis mites.
Burrowing mites induce hypersensitivity, 
causing intense pruritus.
• All in-contact dogs usually affected.
• T ransient pruritus of in-contact other 
species: cats, humans.
SIGNS
• Nonseasonal, progressively worsening 
intense pruritus.
• Pruritus develops within 4–6 weeks of 
exposure.
• Seroconversion 3 weeks after clinical signs 
develop.
• Rare individuals do not seroconvert and 
• Elbows, pinnal margins, ventrum, and 
hocks affected first.
• Crusted papules leading to generalized 
alopecia, crusting, and excoriations; 
lichenification and thickening with 
• Poor response to antihistamines and 
anti-inflammatory doses of steroids.
• Mite numbers often low.
• Immunocompromised individuals may 
harbor larger numbers of mites.
• Close contact with other dogs in animal 
shelters, boarding kennels, groomers, dog 
parks, and veterinary offices.
• Exposure to fox or coyote.
  DIAGNOSIS
• Hypersensitivity dermatitis.
• Parasitic dermatitis (demodicosis, Pelodera , 
Otodectes , Cheyletiella , Trombicula , Dirofilaria ).
• Malassezia  dermatitis.
• Ear margin seborrhea.
ELISA—available in some countries to 
identify Sarcoptes -infested dogs: False positives 
due to crossreactivity with other mites.DIAGNOSTIC PROCEDURES
• Pinnal–pedal reflex—rubbing the ear 
margin between the thumb and forefinger 
induces the dog to scratch with its hind leg.
• Superficial skin scrapings—positive in 
20–50% of scabies cases; false-negative results 
• Fecal flotation—may reveal mites or ova.
• Response to scabicidal treatment—most 
common method for diagnosing scabies.
  TREATMENT
• All in-contact dogs must be treated.
• Resolution of pruritis may take several weeks 
due to hypersensitivity reaction to the mite.
• Sarcoptes  mites usually die quickly in the 
environment; however, mites have been 
reported to survive for up to 3 weeks. 
Thorough cleaning of the dog’s environment 
is recommended in crowded conditions.
• Selamectin—labeled application every 30 
days, or application every 2 weeks for at least 
three treatments.
• Isoxazoline parasiticides (afoxalaner, lotilaner, 
fluralaner or sarolaner)-at labeled dosage/
• Ivermectin 0.2–0.4 mg/kg SC or PO every 
1–2 weeks.
• Milbemycin 2 mg/kg PO every 1–2 weeks.
• Doramectin 0.2–0.6 mg/kg SC or PO weekly.
• Moxidectin 0.2–0.3 mg/kg SC or PO 
weekly; with imidacloprid topical at labeled 
• Lime sulfur 2–4% applied weekly for 4–6 
weeks.
• Fipronil spray applied to entire skin surface 
every 2 weeks for three treatments.
• Topical antiseborrheic therapy in conjunction 
with scabicidal therapy.
resolve secondary pyoderma.
• Prednisolone 1 mg/kg for 5–7 days or longer if 
necessary to relieve pruritus and self-mutilation.
• Ivermectin—do not use/use with caution in 
ABCB1  mutant dogs; increased risk of 
avermectin toxicity in herding breeds: 
Shetland sheepdogs, Old English sheepdogs, 
Australian shepherd dogs, and their crosses.
• Potential increased risk of neurotoxicosis 
with concurrent use of spinosad, macrocyclic 
lactone, or systemic azole medications.
• Isoxazoline parasiticides—potential for 
neurologic adverse events in dogs and cats 
reported.  FOLLOW-UP
• Response to therapy may require 4–6 
weeks.
• Immunity or tolerance does not develop: 
reinfection may occur with subsequent 
contact with infected animals.
• Approximately 30% of dogs with Sarcoptes  
infections will also react to house dust mite 
antigens on intradermal tests. House dust 
mite allergy may be a sequela to scabies 
• Sarcoptic mange is zoonotic. People in close 
contact with an affected dog may develop a 
pruritic, papular rash on body areas in 
frequent contact with dogs.
• Lesions resolve spontaneously when the 
affected animals are treated.
• ELISA = enzyme-linked immunosorbent 
assay.
Becskei C, De Bock F , Illambas J, Cherni JA 
et al. Efficacy and safety of novel oral 
isoxazoline, sarolaner (Simparica™) for the 
treatment of sarcoptic mange in dogs. Vet 
Parasitol 2016, 222:56–61.
Beugnet F , de Vos C, Liebenberg J, Halos H, 
et al. Efficacy of afoxolaner in a clinical field 
study in dogs naturally infested with 
Sarcoptes scabiei . Parasite 2016, 23:26.
Fourie LJ, Heine J, Horak IG. The efficacy of 
an imidacloprid/moxidectin combination 
against naturally acquired Sarcoptes 
scabiei  on dogs. Australian Vet J 2006, 
84:17–21.
Lower KS, Medleau L, Hnilica KA. 
Evaluation of an enzyme-linked immuno-
sorbent assay (ELISA) for the serological 
diagnosis of sarcoptic mange in dogs. Vet 
Dermatol 2001, 12:315–320.
Romero C, Heredia R, Pineda J, et al. 
Efficacy of fluralaner in 17 dogs with 
sarcoptic mange. Vet Dermatol 2016, 
27(5):353–e88.
Resnick

1222  Blackwell’s Five-Minute Veterinary Consult  
SSchiff–Sherrington Phenomenon
  BASICS
OVERVIEW
• Thoracic limb extension associated with 
pelvic limb paralysis or paresis after acute and 
usually severe spinal cord lesion caudal to the 
cervical intumescence, best observed when 
the patient is in lateral recumbency.
• Posture—caused by damage to the border 
cells or their ascending processes, which are 
interneurons located in the lumbar spinal 
cord (mainly L2–4) and normally inhibit the 
extensor motor neurons of the cervical 
intumescence.
Any dog suffering from thoracolumbar spinal 
cord injury.
SIGNS
• Thoracic limbs—rigidly extended; normal 
gait and postural reactions (because the lesion 
is caudal to the cervical intumescence).
• Pelvic limbs—depends on the severity and 
location of the lesion; usually upper motor 
neuron in type, but may be lower motor 
neuron.
• In severe, acute thoracolumbar myelopathies, 
spinal shock may be present in addition to 
the Schiff–Sherrington phenomenon: there is 
an initial flaccid paralysis caudal to the level 
of the lesion, with loss of myotatic and flexor 
reflexes. In dogs and cats, spinal shock is 
uncommon and usually resolves within an 
hour, with more typical signs of upper motor 
neuron disease subsequently developing 
caudal to the spinal cord lesion.
• T rauma secondary to vehicular accident and 
intervertebral disc disease—most common.• Vascular myelopathies (e.g., fibrocartilaginous 
embolism, coagulopathies, etc.).
  DIAGNOSIS
• Decerebrate rigidity—observed with 
brainstem disease in which all four limbs are 
rigid and have upper motor neuron dysfunction; 
opisthotonus present; patient is unconscious.
• Decerebellate rigidity—observed with 
cerebellar disease in which the forelimbs are 
rigid but the hind limbs are flexed; 
consciousness is usually altered.
• Cervical spinal cord injury—may have 
extensor hypertonia in the thoracic limbs; 
upper motor neuron and proprioceptive 
deficits of all four limbs are also seen.
• The key feature in differential diagnosis is 
that in the Schiff–Sherrington phenomenon, 
function and postural reactions in the forelimbs 
are normal despite their extensor rigidity, while 
they are abnormal in the pelvic limbs.
N/A
IMAGING
Radiology (radiography, myelography, CT, 
MRI)—demonstrate the thoracolumbar 
spinal lesion.
  TREATMENT
• Directed toward the underlying 
thoracolumbar spinal cord lesion.
• No specific treatment available.
• Condition resolves if adequate spinal cord 
function is restored.• Schiff–Sherrington phenomenon is not a 
prognostic indicator; prognosis is determined 
by the severity of signs caudal to the spinal 
cord lesion.
As indicated for underlying spinal cord 
disease.
  FOLLOW-UP
• Posture may persist for days to weeks; not 
an indication of a hopeless prognosis.
• With rapid and aggressive treatment, the 
patient may recover, especially if there is pain 
perception caudal to the lesion.
Dewey CW. Functional and dysfunctional 
neuroanatomy: the key to lesion 
localization. In: Dewey CW, ed., A Practical 
ed. Ames, IA: Wiley-Blackwell, 2008, p. 41.

Canine and Feline, Seventh Edition  1223
SSchwannoma
  BASICS
OVERVIEW
Schwannomas are tumors of nerve sheath 
origin, arising from Schwann cells. The term 
peripheral nerve sheath tumor encompasses 
schwannomas, neurofibromas, and neuro­
fibrosarcomas, as these tumors arise from the 
same cell. Importantly, schwannomas are 
grouped with several other soft tissue 
sarcomas (e.g., hemangiopericytoma and 
fibrosarcoma) for therapeutic and prognostic 
purposes, as the biologic behaviors of this 
group of tumors are similar.
• Dogs—median of 10 years, no sex predis  ­ 
position, no known breed predilection.
• Cats rarely affected.
SIGNS
Vary depending on tumor location, which 
can be peripheral (e.g., skin or tongue) or 
more central (e.g., axillary region).
  DIAGNOSIS
• Other neoplasia that can involve the 
connective tissues.
• Other neurologic disease (e.g., interverte­
bral disc disease).
Results usually normal.OTHER LABORATORY TESTS
None
IMAGING
• Myelography may be helpful in cases with 
dorsal or ventral nerve root involvement.
• Contrast CT or, ideally, MRI provides the 
most information regarding extent and 
location of disease.
Electromyography consistently reveals 
abnormal, spontaneous electrical activity in 
muscles of the affected limb.
  TREATMENT
• Surgical excision is the treatment of choice.
• Radiotherapy following incomplete surgical 
resection is likely to result in excellent long ­ 
term outcome.
• Excision of a distal mass may still result in a 
functional limb; amputation is required in 
• Radiotherapy as a single treatment modality 
shows promise for small lesions.
• Laminectomy is necessary in cases of nerve 
root involvement; local recurrence is common 
if the primary extends into the spinal canal.
• Chemotherapy—no successful chemo­
therapeutic management has been described.
• Corticosteroid therapy—may help to 
reduce peritumoral edema and temporarily 
relieve clinical signs.• Gabapentin for neuropathic pain 
alleviation.
N/A
  FOLLOW-UP
• Recurrence common following incomplete 
surgical excision (up to 72% of cases).
• The more distal the tumor, the better the 
possibility of a surgical cure.
• For tumors involving the brachial or 
lumbosacral plexus, median disease ­free 
interval is 7.5 months.
• For tumors involving dorsal or ventral nerve 
roots, median disease ­free interval is 1 month.
• High ­histologic ­grade tumors (e.g., grade 3) 
may metastasize to regional lymph nodes 
or lung.
Chase D, Bray J, Ide A, Polton G. Outcome 
following removal of canine spindle cell 
tumours in first opinion practice: 104 cases. 
J Small Anim Pract 2009, 50:568–574.
Hansen KS,  Zwingenberger AL,  Theon AP , 
et al. T reatment of MRI ­Diagnosed 
T rigeminal Peripheral Nerve Sheath T umors 
by Stereotactic Radiotherapy in Dog. J Vet 
Intern Med 2016;30:1112–1120.

1224  Blackwell’s Five-Minute Veterinary Consult  
SSebaceous Adenitis, Granulomatous
  BASICS
OVERVIEW
• A destructive inflammatory disease process 
directed against cutaneous adnexal structures 
(sebaceous glands).
• May be genetically inherited, immune-
mediated, or metabolic.
• Initial defect—a keratinization disorder or an 
abnormality in lipid metabolism (accumulation 
of toxic intermediate metabolites).
• Young adult to middle-aged dogs; very rare 
in cats.
• T wo forms—long- and short-coated breeds 
(short-coated form now called “idiopathic 
pyogranulomatous periadnexal dermatitis”).
• Predisposed—standard poodle, Akita, 
Samoyed, German shepherd dog, Havanese, 
Bernese Mountain dog and vizsla.
SIGNS
Long-Coated Breeds
• Symmetrical, partial alopecia.
• Dull, brittle hair.
• Tightly adherent silver-white scale.
• Follicular casts around hair shaft (“keratin- 
collaring”).
• Small tufts of matted hair.
• Lesions—often first observed along dorsal 
midline and dorsum of the head.
• Severe—secondary bacterial folliculitis, 
pruritus, and malodor.
• Akitas—often relatively severely affected; 
morbidity associated with deep secondary 
• Standard poodles—affected dogs frequently 
described as having excellent hair coats prior 
to developing lesions; secondary bacterial 
folliculitis rare; most patients do not exhibit 
Short-Coated Breeds
• Alopecia—moth-eaten, circular, or diffuse.
• Mild scaling.
• Lesions often plaque-like.
• Affects the trunk, head, and pinnae.
• Secondary bacterial folliculitis rare.
• Lesions can produce significant scarring.
• Mode of inheritance is being studied; an 
autosomal recessive mode of inheritance is 
documented in the standard poodle and 
suspected in the Akita.
• Multiple pathophysiologic causes theorized 
including autoimmunity against sebaceous 
glands and/or leakage of sebaceous gland 
contents into surrounding dermis causing an 
inflammatory reaction and eventual 
destruction of glands.• Destruction of sebaceous glands may be 
secondary—“innocent bystander” from other 
  DIAGNOSIS
• Primary seborrhea—keratinization 
disorder.
• Endocrine skin disease.
N/A
• Skin scrapings—normal.
• Dermatophyte culture—negative.
• Endocrine function tests—normal.
• Nodular granulomatous to pyogranulo -
matous inflammatory reaction at the level of 
the sebaceous glands.
• Orthokeratotic hyperkeratosis and follicular 
cast formation; more prominent in long-
• Advanced—complete loss of sebaceous 
glands; periadnexal fibrosis.
• Destruction of entire hair follicle and 
adnexal unit rare.
  TREATMENT
• Clinical signs may wax and wane 
irrespective of treatment.
• Controlled studies have not been done to 
document efficacy of any therapy.
• Results extremely variable; response may 
depend on severity of disease at the time of 
• Akita—breed most refractory to treatment.
• Propylene glycol and water—50–75% 
mixture; spray every 24 hours to affected 
areas.
• Baby oil—soak affected areas for 1 hour; 
follow with multiple shampoos to remove oil 
and scales; used monthly or as needed to 
reduce severe accumulations of crusts.
• Frequent bathing with keratolytic 
shampoos (twice weekly).
• EFA supplementation and evening primrose 
oil (500 mg PO q12h); possible side effects 
include vomiting, diarrhea, and flatulence.• Cyclosporine 5 mg/kg PO q12–24h; side 
effects include vomiting, diarrhea, gingival 
lesions, increased incidence of infections, 
nephrotoxicity, and hepatotoxicity.
• Doxycycline 5 mg/kg PO q12h and 
niacinamide 250 mg PO q8h, <10 kg; 
500 mg PO q8h >10 kg with vitamin E.
• Isotretinoin (Accutane) 1 mg/kg PO q12h; 
reduce to 1 mg/kg q24h after 1 month and to 
1 mg/kg q48h after 2 months; continue as 
needed for maintenance; rarely used.
• Bactericidal antibiotics for secondary 
bacterial folliculitis.
Isotretinoin (Accutane)—known teratogen; do 
not use in pregnant dogs; advise owners of risk.
  FOLLOW-UP
Affected dogs should be registered so that 
mode of inheritance can be determined.
Gross TL, Ihrke PJ, Walder EJ. Skin Diseases 
of the Dog and Cat: Clinical and 
Histopathologic Diagnosis. Oxford, UK: 
Blackwell Science, 2005.
2018.
Loss Disorders in Domestic Animals. Ames, 
IA: Wiley-Blackwell, 2009.
Muller and Kirk’s Small Animal Dermatology, 
Resnick

Canine and Feline, Seventh Edition  1225
S
Seizures (Convulsions, Status Epilepticus)—Cats
  BASICS
• Epilepsy—recurrence of seizures from 
primary brain origin. • Genetic epilepsy—
syndrome that is only epilepsy, with no 
neurologic signs; the genetic origin must be 
proven through family studies, gene isolation, 
or other specific forms of evidence (International 
League Against Epilepsy); rare in cats. 
• Structural epilepsy—syndrome in which 
the epileptic seizures are the result of 
identifiable structural brain lesions; frequent 
in cats. • Epilepsy of unknown cause—
structural epilepsy suspected but a lesion 
cannot be demonstrated; frequent in cats. 
• Cluster seizures—>1 seizure/24 hours. 
• Status epilepticus (SE)—continuous seizure 
activity, or seizures repeated at brief intervals 
without complete recovery between seizures. 
Can be nonconvulsive. • Convulsive SE— 
life-threatening medical emergency.
• Paroxysmal disorganization of one or several 
brain functions originating from the 
thalamocortex. Any thalamocortical 
disturbance or disease process may lead to 
seizure activity. • Not all cortical regions have 
the same propensity to seize; from the most to 
the least likely to cause seizures—temporal, 
frontal, parietal, and occipital lobes. • As 
more seizures occur, the tendency for neuronal 
damage and propensity for more seizures or 
SE increases; this kindling effect does not 
occur in all cortical regions. • The clinical 
appearance of the seizure is directly related to 
the location of the neuronal hyperactivity. If 
the electrical abnormality remains regional, 
the seizure is focal. If there is recruitment of 
both hemispheres, the seizure is generalized. 
• Great majority of seizures and SE in cats are 
secondary to structural brain lesions.
Nervous
Unknown
Worldwide
Cats of any breed, age, or sex.
SIGNS
• Nonconvulsive generalized seizures—
frequent in cats; movements of facial 
musculature predominate, such as bilateral 
twitches of eyelids, whiskers and ears, salivation, 
lip smacking; may be associated with whole 
body trembling/shaking, piloerection, dilated 
pupils. Nonconvulsive SE frequent in cats. • Focal seizure—when limited to one 
hemisphere; frantic running and colliding with 
objects (aura), unilateral facial twitches or eyelid 
blinks, unilateral limb motions or head/neck 
turning to one side. Focal seizures often 
generalize. • Generalized convulsive seizures—
bilateral symmetrical tonic–clonic contractions 
of limb muscles and dorsiflexion of the head, 
often associated with autonomic signs such as 
salivation, urination, defecation. At time of 
admission, the gross motor activity may have 
stopped, but there may still be twitching of the 
lids and body/limb jerks. • Mutilation 
frequent—biting of tongue, nail avulsion.
• Confirm that seizure activity has indeed 
occurred. • Pattern of seizures (age at seizure 
onset, type and frequency of seizures)—most 
important factor in listing the possible causes. 
• Metabolic diseases may cause generalized 
seizures (GS). • With most seizurogenic 
toxins, there is a crescendo of hyperexcitability, 
shaking, trembling, with ultimately GS and 
death. • Asymmetry in the signs (eyelid 
twitches, limb movements primarily on one 
side, circling) before, during, or after the 
seizure suggests focal cortical lesion. 
• Overdose of insulin, postrenal transplant, or 
bilateral thyroidectomy lead to GS shortly 
after the fact. • Presence of abnormal behavior 
in the days/weeks preceding the seizure 
activity indicates structural brain disease. 
• Presence of concomitant gastrointestinal 
(GI), respiratory, or other systemic signs 
indicates multisystem disease.
• If chorioretinitis present, look for infectious 
diseases. • Dark red mucous membranes 
suggest polycythemia vera.
• Mental status, menace responses, responses 
to nasal septum stimulation, and proprio -
ceptive positioning are neurologic tests that 
evaluate the cerebral cortex. Asymmetry 
indicates structural brain lesion on the 
contralateral side of the deficits. • In most 
cases of structural epilepsy, neurologic deficits 
are present at presentation.
CAUSES
Extracranial
Metabolic—hypoglycemia from insulin 
overdose, hypocalcemia from bilateral 
thyroidectomy, severe hyperthyroidism, 
hypertension secondary to renal transplant, 
hepatic encephalopathy, uremia, polycythemia 
vera, severe hypertriglyceridemia.
Toxins; Intracranial
• Anatomic—congenital malformation. 
• Metabolic—cell storage disease (e.g., 
neuronal ceroid–lipofuscinosis reported in 
one cat with myoclonus and seizure activity). 
• Neoplastic—meningioma, astrocytoma, 
lymphoma. • Inflammatory infectious—viral non-feline infectious peritonitis (FIP), FIP , 
toxoplasmosis, cryptococcosis. • Toxicity—
organochlorines, pyrethrins, and pyrethroids; 
seizures usually observed at end stage; 
chlorambucil in lymphoma treatment. 
• Vascular—polycythemia vera secondary to 
hyperviscosity, feline ischemic encephalopathy 
secondary to Cuterebra  larva. • T rauma has 
not been linked to seizures in cats.
• Any forebrain lesion. • Diabetes mellitus. 
• T reatment with chlorambucil. • Renal 
failure.
  DIAGNOSIS
• Sleep disorders—the cat does not wake up, 
or has a normal waking behavior following 
the episode. • Syncope—the body is limp 
with a rapid recovery phase, with no 
abnormal behavior. • When seizures are 
preceded by 2–3 weeks of vague transient 
systemic illness (decreased appetite, GI signs) 
in an otherwise healthy cat—viral non-FIP 
encephalitis or epilepsy of unknown cause. 
• When seizures are preceded by systemic 
signs that persist (>3 weeks)—FIP , 
cryptococcosis. • Insidious abnormal 
behavior with/without circling in a cat >10 
years old presented for seizure activity 
suggests meningioma. • Cats with hepatic 
encephalopathy drool excessively. • Cats with 
polycythemia vera have GI signs and dark 
• Extracranial metabolic causes are diagnosed 
on history, physical examination, and blood 
test results. • High packed cell volume 
(>60%) in polycythemia vera. • Low blood 
glucose in insulin overdose. • Low calcium in 
bilateral post thyroidectomy. • High BUN 
and creatinine with low specific gravity in 
acute renal failure. • Creatine kinase—mild 
to markedly elevated in cats with SE, even 
nonconvulsive; with or without 
myoglobulinuria; indicates muscle necrosis.
• Serologic testing—feline immunodeficiency 
virus, feline leukemia virus titers often 
noncontributory to diagnosis; FIP and 
Toxoplasma gondii  titers nonreliable by 
themselves. • Bile acid testing—in cats with 
suspected hepatic encephalopathy.
IMAGING
ultrasound—if infectious disease suspected; 
to evaluate lung pathology if SE; to look 
for neoplasia if tumor suspected. • MRI—
best to define location, extent, and nature 
of lesion.

1226  Blackwell’s Five-Minute Veterinary Consult  
S
CSF—sensitive to detect structural disease; 
unspecific in itself to reach diagnosis except 
when organism is seen (e.g., cryptococcosis).
• Findings reflect etiology. • It is unknown if 
hippocampal necrosis is a cause or the 
consequence of seizures. • Small lesions may 
be easily missed in cats diagnosed with 
epilepsy of unknown cause.
  TREATMENT
• Outpatient—isolated recurrent seizures in 
an otherwise healthy cat. • Inpatient—cluster 
seizures and SE. Isolated recurrent seizures in 
an ill cat.
• Constant supervision. • Install IV line for 
drug and fluid administration. • Draw blood 
for rapid measurement of blood gases, glucose, 
calcium, and antiepileptic drug levels if 
pertinent. • Cool if hyperthermia.
Antiepileptic treatment in structural epilepsy 
may not help until the primary cause is 
addressed. Seizures can be difficult to stop in 
cases of SE, especially with nonconvulsive status.
Craniotomy—tumor excision with 
meningioma or other accessible mass.
Seizure type and frequency determine 
therapeutic approach.
Isolated Recurrent Generalized Seizures
• First line—phenobarbital 7.5–15 mg/cat 
q12h; optimal therapeutic serum levels 
100–130 μmol/L (23–30 μg/L). • Second 
line—gabapentin 3–8 mg/cat q8–12h. 
• Levetiracetam—20 mg/kg q8h (serum 
levels humans 10–40 μg/mL). • Initiate 
gradually to avoid overt sedation.
Convulsive Cluster and Status 
Epilepticus
• T reat cluster and generalized SE early—the 
more seizures in a given time, and the more 
drugs for seizure control, time for recovery, and 
cost for treatment. • No ongoing seizure activity 
at presentation and patient naïve to the drug—  
phenobarbital IV bolus 10 mg/kg to a 
maximum of 60 mg/cat over 15 minutes, 
continued with phenobarbital maintenance 
dosage PO 12 hours later. • Ongoing seizure 
activity at presentation—diazepam IV bolus 0.5–1 mg/kg, continuing with CRI at 0.25–0.5 
mg/cat/h in an inline burette using a fluid 
pump; IV bolus of diazepam can be repeated 5 
minutes after the first bolus if gross seizure 
activity persists; in this case, add phenobarbital 
to CRI at 4 mg/cat/h. • Start oral phenobarbital 
at maintenance dose as soon as patient can 
swallow. • After 6 hours seizures-free, wean CRI 
gradually over 4–6 hours.
Persistent Seizures
Subanesthetic doses of IV propofol 1–3.5 mg/
kg bolus and 0.01–0.25 mg/kg/minute CRI 
titrated to effect.
Non-Antiepileptic Drug Treatment
• Dexamethasone 0.25 mg/kg IV q24h for 
1–3 days, to improve edema secondary to SE 
and treat the primary cause if systemic 
infectious disease is not suspected; 
dexamethasone alters CSF results. 
• Thiamine—5–50 mg/cat in any cat 
presented with acute neurologic signs, 
including seizures.
• Do not use KBr in cats; side effects include 
life-threatening respiratory disease. • Avoid 
giving aminophylline, theophylline, ketamine, 
and fentanyl to epileptic cats.
• Prolonged use of propofol (>24 hours) may 
cause Heinz body anemia in cats. • Cats on 
CRI of antiepileptic drug(s) are often overtly 
sedated; cardiovascular and respiratory 
depression may occur; close monitoring 
necessary; lubricate eyes, express bladder 
manually, correct hypothermia. • Close 
monitoring necessary to observe if mild 
ongoing seizure activity persists.
N/A
• Zonisamide—5–10 mg/kg PO q24h 
(serum levels humans 15–45 μg/mL). 
• Diazepam—0.5–2.0 mg/kg/day PO 
divided q12h.
  FOLLOW-UP
• CBC, biochemistry, urinalysis prior to 
initiating antiepileptic drug. • Phenobarbital-
induced hepatotoxicity is not a problem in 
the cat. • Creatine kinase to evaluate 
muscular necrosis and indirectly subtle 
ongoing seizure activity in cats presented in 
SE. • Measure phenobarbital serum level 2 
weeks after initiation; correct dosage 
accordingly; it is difficult to titrate 
phenobarbital in cats, i.e., a mild increase in 
dosage often leads to a major increment of 
the serum levels. • CBC and biochemistry—repeat every 6–12 months. • If structural 
epileptic patient has recovered from primary 
disease and remains seizure-free for 6 
months—seizures may recur when drug is 
weaned off.
• SE—seizure control may not be reached 
despite polypharmacy. • Rare hypersensitivity 
to phenobarbital—thrombocytopenia, 
neutropenia, pruritus, swollen feet; do CBC 
4–6 weeks after onset of phenobarbital. 
• Diazepam rarely may cause acute hepatic 
necrosis and death. • Cardiovascular and 
respiratory collapse from overdose during SE 
• Depends on the underlying cause and 
response to treatment. • Cats with epilepsy of 
unknown cause have good long-term prognosis. 
• Cats can recover despite episode of severe 
cluster-seizures and generalized SE.
Cats with seizure onset prior to 1 year of age 
and diagnosed with epilepsy of unknown 
cause have guarded prognosis for seizure 
control.
SEE ALSO
• Feline Ischemic Encephalopathy. 
• Meningioma—Cats and Dogs.
• GS = generalized seizures.
• SE = status epilepticus.
Barnes HL, Chrisman CL, Mariani CL, et al. 
Clinical signs, underlying cause, and 
outcome in cats with seizures: 17 cases 
(1997–2002). J Am Vet Med Assoc 2004, 
225:1723–1726.
Pakozdy A, Gruber A, Kneissl K, et al. 
Complex partial cluster seizures in cats with 
orofacial involvement. J Feline Med Surg 
2011, 13:687–693.
Parent J. Seizures and status epilepticus in 
cats. In: Veterinary Emergency and Critical 
Care Manual, 2nd ed. Guelph, Ontario: 
Lifelearn, 2006, pp. 456–459.
Wahle AM, Brühschwein A, Matiasek K, 
et al. Clinical characterization of epilepsy of 
unknown cause in cats. J Vet Intern Med 
2014, 28:182–188.
available onlineSeizures (Convulsions, Status Epilepticus)—Cats  (continued)

Canine and Feline, Seventh Edition  1227
SSeizures (Convulsions, Status Epilepticus)—Dogs
  BASICS
primary brain origin.
• Genetic epilepsy—epilepsy with no 
observable underlying brain lesion or other 
neurologic signs or symptoms.
• Structural epilepsy—seizures are the result 
of identifiable structural brain lesions.
• Epilepsy of unknown cause—structural 
epilepsy is suspected but a lesion cannot be 
• Cluster seizures—>1 seizure/24 hours.
activity or seizures repeated at brief intervals 
without complete recovery between seizures.
• SE can be convulsive or nonconvulsive.
• Seizures are classified as focal (limited to 
one hemisphere), generalized (involve both 
hemispheres), and focal with secondary 
generalization.
• Any thalamocortical disturbance may lead 
to seizure activity.
• Not all cortical regions have equal 
propensity to seize; from the most to the least 
likely to cause seizures—temporal, frontal, 
parietal, and occipital lobes.
• As more seizures occur, the tendency for 
neuronal damage and propensity for more 
seizures or SE increases; this kindling effect 
does not occur in all cortical regions.
• The clinical appearance of a seizure is 
related to the location of the neuronal 
hyperactivity.
• Dogs of any breed, age, or sex.
• SE—overrepresentation of German 
shepherd dog, English foxhound, pug, teacup 
poodle, Boston terrier, Lakeland terrier.
SE—4.2–5 years (0.15–15 years).
SIGNS
• Prodrome—hours to days prior to the 
seizure; no electroencephalogram (EEG) 
changes.
• Aura—short period (seconds) prior to 
generalization of a seizure where the dog seeks 
help, looks lost, frightened or has a glazed look. 
Focal seizure. If it precedes the tonic–clonic 
generalized seizure, the seizure has a focal onset.
• Ictus—may start with an aura and progress 
to generalized seizure (GS); lateral recumbency 
with bilateral symmetrical tonic–clonic 
contractions of limb muscles; often with 
autonomic signs, e.g., salivation, urination, 
defecation.• GS—may be mild, the animal remaining 
sternal or even standing during the event; 
may be long-lasting, 20 minutes or more. 
Convulsive or nonconvulsive.
• Post-ictal phase—disorientation, confusion, 
aimless pacing, blindness, polydipsia, polyphagia.
• A seizure lasts <2 minutes.
• Most seizures occur when dog is resting or 
sleeping.
• Confirm that seizure has occurred.
• Seizure pattern (age at onset of seizure, 
seizure type and frequency)—most important 
factor in establishing list of possible causes.
• Metabolic diseases usually cause generalized 
seizures.
• Asymmetric neurologic signs before, during, 
or after the seizure suggest structural brain lesion.
• Presence of behavioral changes in the days/
weeks preceding seizure onset indicates 
structural brain disease.
• Mental status, menace responses, responses to 
nasal septum stimulation, and proprioceptive 
positioning—neurologic tests that evaluate the 
cerebral cortex. Asymmetry indicates structural 
brain lesion contralateral to deficits.
• Compensated SE, first 30 minutes—
salivation, hyperthermia, tachycardia, 
arrhythmia, increased blood pressure.
• Decompensated SE—difficulty breathing, 
weak pulse, low blood pressure, poor capillary 
refill.
CAUSES
• Metabolic—electrolyte disturbances, 
hypoglycemia (insulinoma); hypocalcemia; 
acute renal failure; hepatic encephalopathy.
• Toxicities—metaldehyde, pyrethrins/
pyrethroids, lead, hexachlorophene, chlorinated 
hydrocarbons, organophosphates, bromethalin, 
mycotoxins, macademia nut, theobromine 
(chocolate), 5-fluorouracil.
• Degenerative—encephalopathy.
• Malformations—cortical dysplasia.
• Genetic epilepsy.
• Metabolic—cell storage diseases.
• Neoplasia—primary (meningioma, 
gliomas); secondary (metastatic).
• Inflammatory infectious—viral (e.g., canine 
distemper); fungal; protozoal ( Neospora , 
Toxoplasma ); rickettsial (ehrlichiosis, Rocky 
Mountain spotted fever).
• Inflammatory noninfectious—
meningoencephalomyelitis of unknown origin, 
eosinophilic meningoencephalomyelitis; 
breed-related encephalitis (pug, Maltese, 
Yorkshire terriers, etc.).
• T rauma.
• Vascular—cerebrovascular accident.• Epilepsy of unknown cause—post -
encephalitic glial scar.
  DIAGNOSIS
• Syncope—body is limp, rapid recovery with 
no abnormal behavior; occurs at exercise, 
cough, excitement.
• Insulinoma—seizures occur at exercise, 
• Obsessive compulsive behaviors or 
stereotypes—complex and goal-directed 
behaviors; behavior can be stopped.
• Seizurogenic toxins—progression from 
whole body tremor to SE and death if left 
• Metabolic encephalopathy—seizures 
unusual and accompanied with obtunded 
mental state and abnormal behavior; no 
lateralizing signs.
• Structural brain disease likely—if acute onset 
of >2 GS within first week of onset, acute 
onset of focal seizures with gradual progression 
to GS, or presence of interictal neurologic 
deficits including behavioral changes.
• Genetic epilepsy—differentiated on age, 
breed, and seizure pattern; progressive onset 
of GS with/without aura.
• Cervical pain/spasms—may be mistaken for 
focal seizures.
• Head bobbing or idiopathic head tremor—
dog remains active; can eat, drink, walk.
• Infectious CNS diseases—may reflect 
multisystem involvement.
• Hypoglycemia—small/toy breeds during 
SE; insulinoma.
• Hepatic and renal dysfunction—advanced SE.
• Urinalysis—rule out myoglobinuria.
• Blood gases—metabolic acidosis frequent 
with SE. Respiratory acidosis needs 
immediate treatment.
• Coagulation profile—disseminated 
intravascular coagulation (DIC) in advanced SE.
• Bile acids—suspected hepatic encephalopathy.
• Fasting blood glucose and amended insulin: 
glucose ratio—dogs >5 years with occasional 
seizures during exercise.
• Serology (infectious diseases)—as suggested 
by systemic signs and laboratory abnormalities.
• Toxicity screen—cholinesterase levels.
IMAGING
ultrasound—to identify metastatic or 
systemic illness, or lung pathology from SE.
• MRI—best to define location, extent, and 
nature of lesion.

1228  Blackwell’s Five-Minute Veterinary Consult  
SDIAGNOSTIC PROCEDURES
Electrocardiogram (ECG)—arrhythmias  
can occur in SE due to myocardial  
damage. CSF—if intracranial structural 
cause is suspected; CSF and serum titers  
and PCR for diagnosing infectious  
diseases. EEG—to document ongoing  
seizure activity once physical manifestations 
have ceased.
  TREATMENT
• Outpatient—isolated seizures in an 
otherwise healthy dog.
• Inpatient—cluster seizures and SE.
• SE and cluster-seizures—constant 
supervision.
• Ensure airway patency. May need to be 
suctioned due to excessive salivation.
• Administer 100% oxygen via non-
rebreathing mask.
• Cool down if hyperthermia.
• Install IV line for drug and fluid 
• Draw blood for rapid measurement of 
blood gases, glucose, calcium, renal and 
hepatic function, and antiepileptic drug 
(AED) levels if pertinent.
• Monitor urine output with indwelling 
urinary catheter.
• T reat cluster of GS and generalized status 
epilepticus (GSE) early—the more seizures in 
a given time, and the more drugs for seizure 
control, time for recovery, and cost for 
• Antiepileptic treatment in structural 
epilepsy may not help until the primary cause 
is addressed.
• Client to keep a seizure calendar noting 
date, time, severity, and length of seizures to 
objectively evaluate response to treatment.
• Outline an in-home treatment emergency 
plan for cluster-seizures.
• Electrolytes imbalance—treat immediately 
with fluid therapy.
• Low glucose—50% dextrose diluted to 
25% (500 mg/kg IV) over 15 minutes or treat 
with oral glucose syrup.
Seizure type and frequency determine the 
therapeutic approach. Important to seek and 
treat primary cause.Convulsive Cluster Seizures or Status 
Diazepam
• Administer 0.5–1 mg/kg IV bolus; repeat 5 
minutes later if gross motor activity has not 
subsided; follow with CRI of 0.5–1 mg/kg/h 
added to hourly maintenance fluids in an 
inline burette or through syringe pump.
• Rectal—only where IV access cannot be 
obtained; may diminish or stop gross motor 
seizure activity to allow IV catheter placement.
• Refractoriness may rapidly develop, 
necessitating the addition of phenobarbital CRI.
• Add if seizures persist after second 
diazepam bolus or during diazepam CRI; 
administer CRI phenobarbital (2–6 mg/
dog/h added to diazepam infusion) if patient 
already treated with phenobarbital, or loading 
dose if patient naïve to phenobarbital.
• Loading dose—12–24 mg/kg given as 
boluses of 4 mg/kg IV, 20 minutes apart until 
desired effect is reached, to a maximum of 24 
mg/kg. Optimal therapeutic range—100–120 
μmol/L (23–28 mg/L).
• If patient already on phenobarbital, obtain 
serum level prior to initiating phenobarbital 
CRI. IV bolus 2–6 mg/kg can be administered 
once while awaiting results if serum levels 
believed inadequate.
• Once seizures have been controlled for 4–6 
hours, gradually wean the patient off CRI 
over as many hours.
• Start/resume oral maintenance AED using 
phenobarbital and/or other GS AED as soon 
as patient can swallow.
Other
• If seizures continue, propofol at 1–2 mg/kg 
IV slowly over 60 seconds, followed by CRI 
at 0.1–0.6 mg/kg/min to effect; monitor 
anesthetized patient with EEG to evaluate 
• Ketamine is also used occasionally at 5 mg/
kg IV bolus followed by CRI at 5 mg/kg/h.
• Dexamethasone—0.2 mg/kg q24h for 1–3 
days; reduce cerebral edema.
• Dexamethasone—for acute treatment of 
cerebral edema secondary to severe inflamm -
atory CNS disease, even if infectious.
Acute Focal Status Epilepticus
• Often harbors brain lesion.
• Diazepam and phenobarbital CRI—
effective for focal and GS.
• Frequently difficult to reach seizure control.
• Instances of chronic nonconvulsive 
generalized or focal SE—owner unaware it is 
occurring (e.g., senile encephalopathy); if 
seizures remain focal and patient’s quality of 
life not significantly altered, no treatment 
necessary. Long-term antiepileptic treatment 
if necessary—phenobarbital 3–5 mg/kg q12h 
PO, levetiracetam 20 mg/kg q8h PO, or 
zonisamide 5 mg/kg q12h PO.CONTRAINDICATIONS
• Potassium bromide—do not use to treat 
SE; too long half-life; loading dose not 
• Aminophylline, theophylline—CNS 
excitement; may cause seizure.
• Steroids—alter CSF parameters; avoid if 
considering CSF analysis.
• Phenobarbital—liver disease, lower dose; 
monitor levels closely; for SE, add cautiously to 
diazepam because the drugs potentiate each 
other, cardiac/respiratory depression may ensue.
• Steroids—contraindicated in infectious 
diseases, but one dose of dexamethasone 0.2 
mg/kg IV may decrease brain edema when 
impending brain herniation or life-
threatening edema is suspected.
• Cimetidine, ranitidine, and 
chloramphenicol—interfere with 
phenobarbital metabolism; may lead to 
phenobarbital toxic level.
• Phenobarbital decreases zonisamide serum 
levels. Dosage recommended when drugs are 
used simultaneously—10 mg/kg q12h.
• If levetiracetam used concomitantly with 
phenobarbital—measure serum levels 
(humans 10–40 μg/mL).
Levetiracetam—20–60 mg/kg IV; use upper 
end dosage if patient already on oral 
phenobarbital. Good alternative in liver 
disease or portosystemic shunts, as the drug is 
not metabolized in the liver. Use with caution 
in patients with renal disease.
  FOLLOW-UP
• Inpatients—constant supervision for seizure 
• Eyelid or lip twitching in a heavily sedated 
patient is sign of ongoing seizure activity.
• Monitor heart rate, respiratory rate, 
oxygenation/ventilation, body temperature, 
blood pressure, urine production, neurologic 
• EEG monitoring for ongoing seizure activity.
• Patient may need 7–10 days before 
returning to normal after SE.
• Phenobarbital—hepatotoxicity after 
long-term treatment with serum levels >140 
μmol/L (>33 μg/L); acute neutropenia (rare) 
in the first few weeks of use requires 
permanent withdrawal.
• Paradoxical hyperexcitability.
• Permanent neurologic deficits (e.g., 
blindness, abnormal behavior, cerebellar 
signs) may follow severe SE.Seizures (Convulsions, Status Epilepticus)—Dogs  (continued)

Canine and Feline, Seventh Edition  1229
S• GSE may lead to hyperthermia, acid–base 
and electrolyte imbalances, pulmonary 
edema, cardiovascular collapse, and death.
• Genetic epilepsy or epilepsy of unknown 
cause represents a large proportion of dogs 
with GSE or cluster-seizures. In-home 
emergency measure using diazepam rectal/
nasal should be provided.
• Dogs with encephalitis and GSE—poor 
outcome.
• Structural epileptic dogs recovered from 
primary disease (e.g., Ehrlichia canis )—
slowly (over months) wean patient off AEDs after 6 months seizure-free; if seizures recur, 
reinstate AED.
• The immature brain has a higher 
propensity to seize.
• Genetic epilepsy—6 months–5 years; often 
epilepsy refractory when onset at <2 years.
• Phenobarbital—higher dose needed in 
puppies (<5 months) to reach therapeutic range.ABBREVIATIONS
• EEG = electroencephalogram.
• GS = generalized seizure.
• GSE = generalized status epilepticus.
Author  Joane M. Parent 
available online(continued)  Seizures (Convulsions, Status Epilepticus)—Dogs

1230  Blackwell’s Five-Minute Veterinary Consult  
SSeminoma
  BASICS
OVERVIEW
Sex cord stromal tumor of the testicle arising 
from the spermatic germinal epithelium.
• Boxer, German shepherd dog, Afghan 
hound, Weimaraner, Shetland sheepdog, 
collie, and Maltese may be at increased risk.
• 33–52% of all testicular tumors in dogs; 
extremely rare in cats.
SIGNS
• Usually none.
type of testicular tumor.
• Up to 50% of dogs will have bilateral 
tumors, only 12% of contralateral tumors will 
be palpable.
Cryptorchidism
  DIAGNOSIS
• Interstitial (Leydig cell) cell tumor.
Usually normal unless hormone productive 
and consequent male feminization syndrome.IMAGING
tial diagnosis.
• Abdominal sonography for retained testicles 
and to evaluate for concurrent malignancies.
N/A
  TREATMENT
• Exploratory laparotomy for retained 
testicles.
tissue.
• Radiotherapy—reported effective in 
patients with regional metastasis.
None reported in dogs.
  FOLLOW-UP
Castration at a young age.POSSIBLE COMPLICATIONS
None likely.
often curative. Reported rate of region or 
distant metastasis <15%.
• Prostate disease.
• Perianal adenoma.
SEE ALSO
• Interstitial Cell T umor, Testicle.
Grieco V, Riccardi E, Greppi GF , et al. 
Canine testicular tumours: a study on 232 
dogs. J Comp Pathol 2008, 138(2–3): 
86–89.
Small Animal Clinical Oncology. St Louis, 
MO: Elsevier Saunders, 2013, 
pp. 557–571.

Canine and Feline, Seventh Edition  1231
SSeparation Anxiety Syndrome
  BASICS
A distress response of dogs (occasionally cats) 
separated from the person or persons to 
whom they are most attached, usually their 
owner(s). The separation may be real (the 
owner is gone) or perceived (pet is separated 
from the owner). In other cases the pet may 
be distressed because a fear-inducing event 
has occurred while home alone (e.g., 
thunderstorms, loud noises or home 
invasions), resulting in distress responses 
during subsequent departures. Distress may 
be exhibited as destruction, vocalization, and 
elimination in the owner’s absence. Separation 
anxiety is a subset of separation-related 
problems that may have different underlying 
motivations, including fear, anxiety, 
overattachment to owner(s), and lack of 
appropriate stimulation or interactions.
Unknown but suspected changes in brain 
pathology due to aging, anxious temperament, 
noise or location phobias, insecure attachment 
to humans in family.
• Behavioral—escape attempts, howling, 
whining, depression, hyperactivity.
• Endocrine/metabolic—increased cortisol, 
stress-induced hyperglycemia.
• Gastrointestinal—inappetence, diarrhea, 
vomiting
• Musculoskeletal—self-induced trauma from 
escape attempts.
• Nervous—adrenergic/noradrenergic 
overstimulation.
• Skin/exocrine—acral lick dermatitis.
• Oral—dental damage during escape 
attempts.
GENETICS
It is speculated that 13–28% of companion 
dogs experience some degree of separation 
anxiety. May be different underlying 
pathology with young dogs and senior dogs.
Species
Primarily dogs; possible in cats.
Any age, most commonly in dogs >6 months; 
may be another increase in prevalence in dogs 
>8 years.
Male and neutered male dogs overrepresented 
in recent studies.SIGNS
Destruction, vocalization, and elimination in 
the absence of the owner alone are not 
diagnostic for separation distress.
• Destruction, vocalization (whining, howling, 
barking), and indoor elimination. Destruction 
targets windows and doors and/or owner 
possessions.
• Other signs include behavioral 
depression, anorexia, drooling, hiding, 
shaking, panting, pacing, attempts to 
prevent owner departure, and self-trauma 
from lick lesions. Diarrhea and vomiting 
are occasionally seen.
• Signs of strong pet–owner attachment may 
be present: excessive attention-seeking 
behaviors and following behaviors are not 
necessary for diagnosis and do not occur in all 
patients.
• Frequently owners report excessive, 
excited, and prolonged greeting behavior 
upon return.
• Separation anxiety behavior(s) usually 
occurs regardless of the length of owner 
absence, often within 15–30 minutes of 
owner departure.
• Specific triggers that are predictive of 
possible departure may initiate the anxiety 
response: getting keys, putting on outer 
garments, or packing the car but are not seen 
in all patients.
• May occur on every departure and absence 
or only with atypical departures, e.g., after- 
work, evening, or weekend departures; the 
reverse pattern may also be seen.
• Some animals may initially show signs in 
the presence of acute fear- or anxiety-
inducing events such as thunderstorms or 
fireworks when home alone but may recur 
with future departures even in the absence 
of stimuli.
• In cats, elimination problems in the owner’s 
absence may be linked to separation-related 
anxiety.
• May be excessive water consumption upon 
owner return.
• Distress may also be initiated by a change 
in daily routine or in the household (e.g., 
moving house).
• What appears as distress may also be 
frustration at being alone, being confined, 
inability to pursue other activities, living in 
an impoverished environment or lack of 
• Injuries may be incurred in escape attempts 
or destructive activities.
• Skin lesions from excessive licking.
• Rare cases of dehydration from drooling or 
diarrhea due to stress.CAUSES
Specific causes unknown. Causal factors may 
include:
• Insecurity or anxiety about owner departure 
and absence.
• Frustration due to lack of the ability to 
engage in normal behaviors (lack of 
enrichment, exercise or social contact).
• Lack of appropriate pet–owner 
• Prolonged contact with humans without 
learning how to be alone.
• Improper or incomplete early separation 
from the bitch (French behavior school).
• T raumatic episodes during owner absence.
• Concurrent anxiety disorders, e.g., noise 
and storm fears and phobias.
• Change in household routine/schedule.
• Medical issues contributing to anxiety, 
including endocrine dysfunction, pain, 
sensory decline, or cognitive decline.
• Suspected risk factors—adoption from 
humane shelters, extended time with 
preferred person such as during vacation or 
illness, boarding, lack of detachment when 
young.
• Geriatric animals seem to be overrepresented.
• Possible correlation between separation 
anxiety and other anxiety disorders including 
noise phobias.
  DIAGNOSIS
• Vocalization—response to outdoor stimuli, 
territorial displays, play with other pets in the 
home, fears.
• Destructive behaviors—occur both when 
the owner is present and absent (e.g., territorial 
destructive displays at windows and doors; 
destruction due to fear-producing stimuli such as 
noises and thunderstorms). Lack of appropriate 
outlets for normal chewing and play.
• Housesoiling—inadequate housetraining, 
illness, endocrine dysfunction, cognitive 
decline.
• Fear-based conditions.
• Barrier frustration—dogs unable to be 
confined in crates or behind barriers but are 
fine if not confined.
endocrinopathies, sensory decline, pain, 
cognitive dysfunction syndrome, and 
dermatologic conditions leading to self- 
trauma.
Indicated to rule out concurrent medical 
conditions and as baseline prior to 

1232  Blackwell’s Five-Minute Veterinary Consult  
SOTHER LABORATORY TESTS
Endocrine testing if indicated by history, 
examination and/or CBC/biochemistry 
results.
IMAGING
MRI or CT if neurologic disorders are 
• Behavioral history using standard 
questionnaires.
• Video recordings of the pet when home 
alone to verify diagnosis.
• Questionnaires targeting cognitive decline 
are advisable for geriatric dogs.
• Endoscopy with biopsy if gastrointestinal 
signs.
  TREATMENT
ACTIVITY
• Regular, scheduled daily exercise and 
playtime.
• Enriching the environment with toys that 
are interactive and/or dispense food.
DIET
None unless gastrointestinal signs.
Once other causes of destruction and 
elimination have been ruled out or addressed, 
it is important to help the owner understand 
that the destruction or elimination is due to 
anxiety and not spite. Set a realistic expect -
ation of the time course of treatment and the 
need for behavior modification to have 
successful resolution of the problem. Problem 
behavior may take weeks or months to 
resolve, depending on severity and duration 
of the problem. T reatment may include some 
or all of the following.
Independence Training
• Teach the dog to remain calm when not in 
close proximity to the owners to encourage 
the dog to be more independent of the 
owner(s).
• Teach the dog to calmly stay in a location 
away from the owner and create a safe haven 
for the dog to settle and relax on command. 
Initially this can be a dog bed on the floor 
1–2 feet from the owner. The dog must be 
calm and relaxed when the owner is home for 
gradually longer times and gradually 
increasing separation to be calm and relaxed 
when they are gone.
• When possible, and without creating more 
anxiety, cue a behavior such as “sit” prior to 
attention or affection. Longer and more 
relaxed responses can be very gradually 
shaped.• When possible, decrease following behavior 
while the owner is home, perhaps by sending 
the dog to the safe bed or mat to wait and 
reinforcing with attention and treats.
• Owners should strive to give attention in a 
predictable and calm manner—requesting a 
sit or other calm behavior such as down 
before petting, giving treats or chews, 
throwing a ball, going out for a walk, etc.
Changing the Predictive Value 
of Pre-Departure Cues
• Some dogs begin to get anxious when they 
see cues that indicate owner departure.
• For those dogs, presentation of pre-
departure cues (picking up keys, walking to 
the door) without leaving may be helpful; but 
not if it causes increased anxiety.
• Repeat 2–4 times daily until the dog does 
not respond to cues with anxious behaviors 
(panting, pacing, following, or increased 
vigilance).
• Goal is to disassociate the cues with 
departures and diminish the anxious 
response. If the dog becomes more anxious, 
this step is discontinued.
Counter-Conditioning
• Teach the dog to sit/stay near the typical 
exit door.
• Owner gradually increases the distance 
between the dog and the exit door.
• Owner slowly progresses toward the door, 
increasing the time away on each trial.
• Eventually elements of departure, such as 
opening and closing the door, are added.
• Finally, the owner steps outside the door 
and returns.
Classical Counter-Conditioning
• Pairing favored treats with departure cues. 
Leaving the dog a delectable food treat or 
food-stuffed toy on departure.
• Associating departure with something 
pleasant.
Changing Departure and Return Routine
• Passively ignore the pet for 15–30 minutes 
prior to departure and upon return.
• On return, attend to the dog only when it 
is calm and quiet.
• Allow the dog outside to eliminate.
Graduated Planned Departures 
and Absences
• Begun after dog is not responding anxiously 
to pre-departure cues.
• Use short absences to teach the dog how to 
be home alone.
• Departures must be short enough not to 
elicit a separation anxiety response; the pet 
must be calm when owners depart and calm 
when they return.
• Goal—animal learns consistency of owner 
return and to experience departure and 
absence without anxiety.• Departures must be just like real departures 
(owner must do all components of departure, 
including leaving in the car if that is how he 
or she usually departs).
• Owner can leave a safety cue (radio or 
television on, ring a bell) on planned 
departures only (must not be used on 
departures where length of absence is not 
controlled, such as work departures).
• Initial departures must be very short, 
1–5 minutes.
• Length of absence is slowly increased at 
3–5 minute intervals if no signs of distress 
at the shorter interval (excited greetings, 
barking etc.).
• Increase in interval must be variable; 
intersperse short (1–3 minute) with longer 
(5–20 minute) departures.
• If destruction, elimination, or vocali -
zation occurs, the absence was too long. Use 
video recordings, remote monitoring or 
audio recordings of vocalization to assess pet 
anxiety and monitor progress.
• Once the pet can be left for 2–3 hours on 
a planned departure, it often can be left 
all day.
• Cue can be slowly phased out over time or 
can be used indefinitely.
Arrangements for the Pet During 
Retraining and Owner Absence
• If possible, prevent further departures that 
lead to anxiety.
• If departures and absences are continued 
while distress behaviors are present, the 
problem will get worse.
• Mixing up or eliminating triggering 
departure cues may help diminish the anxious 
• Doggie daycare arrangements or pet sitters.
• Gradual positive conditioning to a crate as a 
safe haven if the dog is not distressed and will 
settle.
• Crates must be used cautiously if at all and 
only in dogs that are calm when left in a crate 
as they may increase anxiety, resulting in pet 
injury.
If animal is on medication, use caution prior 
to administering anesthesia.
Drugs for Chronic (Ongoing) Therapy
Clomipramine (Branded product 
“ClomicalmTM”)
• T ricyclic antidepressant (TCA)—approved 
for use in the treatment of separation anxiety 
in dogs.Separation Anxiety SyndromeSeparation Anxiety Syndrome  (continued)

Canine and Feline, Seventh Edition  1233
S• Dosage—dogs: 2–4 mg/kg daily; dogs may 
do better with dividing the dose and 
administering twice daily. Must be given 
daily, not on an “as needed” basis, and in 
conjunction with a behavior modification 
plan.
• May take 2–4 weeks before behavioral 
effect is evident.
• Side effects—vomiting, diarrhea, and 
lethargy.
Fluoxetine (Branded product ReconcileTM)
• Selective serotonin reuptake inhibitor 
(SSRI)—approved for use in the treatment of 
separation anxiety in dogs.
• Dosage—1–2 mg/kg PO q24h.
• Administer in conjunction with a behavior 
modification plan.
• Side effects—lethargy, decreased appetite, 
weight loss, and vomiting.
Drugs for Acute Anxiety at Departure
• While waiting for SSRI or TCA effect, 
concurrent use of short-term anxiolytics 
and pheromones is advisable in most  
cases.
• Benzodiazepines—alprazolam for panic at 
owner departure (dog, 0.01–0.1 mg/kg) 
30 minutes prior to departure. Some dogs 
experience paradoxical excitement with 
benzodiazepines, which may resolve with 
altered dosage or change to another 
benzodiazepine. Polyphagia is also common 
with benzodiazepine administration.
• T razodone—a serotonin receptor 
antagonist and reuptake inhibitor and can 
be used in conjunction with a TCA or SSRI 
to augment calming effects. Dosage 
recommendation (dog) is to begin with 2–3 
mg/kg PO prior to departure and titrate up 
gradually to effect (up to 8–10 mg/kg). 
Dose should be increased cautiously, 
especially if using with an SSRI or TCA 
due to potential for serotonin syndrome. 
Side effects include vomiting, diarrhea, 
sedation, ataxia, hypotension, excitement 
or agitation and panting and rare reports of 
• Dog-appeasing pheromone (Adaptil)—  
synthetic analogue of the maternal appeasing 
pheromone; may calm dogs in fearful, stressful, 
and anxiety situations such as separation 
anxiety and noise phobias; available as a 
plug-in diffuser for dog’s housing area, a spray 
for the cage or mat, and collar.
• Clomipramine and fluoxetine should not 
be used in combination or combined with 
monoamine oxidase inhibitors (MAOIs) such 
as amitraz and selegiline or within 14 days 
after an MAOI.
• Use clomipramine with caution in 
patients showing cardiac conduction 
disturbances.• Caution advised using in conjunction with 
CNS-active drugs, including general 
anesthesia, neuroleptic, anticholinergic, and 
sympathomimetic drugs for dogs on either 
clomipramine or fluoxetine.
• A 6-week washout interval should be 
observed following discontinuation of 
fluoxetine prior to administration of any drug 
that may interact with fluoxetine.
dogs with epilepsy or with drugs that lower 
the seizure threshold (phenothiazines).
• Studies to determine effects of medication 
in patients less than 6 months of age have not 
been conducted.
• Studies to assess the interaction of 
fluoxetine with TCAs have not been 
conducted.
• Improperly applied behavioral modification 
may increase anxiety.
• Crating can result in serious physical 
damage to the pet if it attempts to 
escape; should only be recommended 
cautiously for animals that are already 
crate-trained.
Serotonin syndrome with combinations of 
MAOI and SSRI or SSRI and TCA.
• TCA such as amitriptyline (dog, 1–2 mg/kg 
q12h) might be considered in place of 
• Clonidine—an alpha-2 agonist which 
might be used prior to departures in 
combination with a TCA or SSRI at a 
dose of 0.01–0.05 mg/kg. Begin at the 
lowest end of the dose range and increase 
cautiously.
adjunctively—alpha-casozepine alone or  
in a diet with l-tryptophan; l-theanine 
alone or in combination products containing 
whey protein, Phellodendron amurense , 
and Magnolia officinalis ; melatonin; 
S-adenosyl methionine; Souroubea  and 
Plantanus  products; probiotic calming 
supplement; lavender aromatherapy; classical 
musical.
  FOLLOW-UP
Good client follow-up is necessary to 
monitor both the behavioral treatment plan 
and medication if prescribed. Weekly 
follow-up is best in the early stages to assess 
efficacy of the treatment plan and owner 
compliance. Once the dog has become more 
independent, habituated to pre-departure cues, and calmer on departures and returns, 
graduated planned departures may be 
implemented.
Habituating to spending time alone, safe 
haven training, training independence.
• Injuries during escape attempts.
• Ongoing destruction and elimination 
disrupt the human–animal bond and result in 
pet relinquishment.
• Other anxieties causing signs that mimic 
separation distress; if not identified and 
treated, the problem may worsen.
Separation anxiety often responds well to 
behavioral modification with or without 
medication. Some cases can be very resistant 
to treatment. Other concurrent behavioral 
disorders may make resolution more difficult. 
Drug therapy alone is rarely curative for most 
behavioral disorders. Realistically, drug 
therapy can be expected to decrease the 
anxiety associated with owner departure, but 
the dog still must be taught how to accept 
and be comfortable left alone during owner 
absences.
Other anxiety conditions, including noise 
phobias, generalized anxiety, fears, and 
compulsive disorders.
May be increased prevalence in senior  
dogs.
SYNONYMS
Hyperattachment–separation distress.
SEE ALSO
• Excessive Vocalization and Waking at 
Night—Dogs and Cats.
• Fears, Phobias, and Anxiety—Dogs.
Horwitz DF (ed.) Blackwell’s Five-Minute 
Hoboken: NJ. John Wiley & Sons, 2018, 
pp. 348–362.
Horwitz DF . Separation-related problem in 
dogs and cats. In: Horwitz DF , Mills DS, (continued)  Separation Anxiety Syndrome

1234  Blackwell’s Five-Minute Veterinary Consult  
Seds., BSAVA Manual of Canine and 
Feline Behavioural Medicine, 2nd ed. 
Gloucester, UK: BSAVA, 2009, pp. 146–158.
Fears, phobias and anxiety disorders. In: 
ed. St. Louis, MO: Saunders/Elsevier, 2013, 
pp. 181–210.Overall KL. Manual of Clinical Behavioral 
Medicine for Dogs and Cats. Ames, IA: 
Elsevier, 2013, pp. 238–261.
Storengen LM, Boge SCK, Strøm SJ, et al. 
A descriptive study of 215 dogs 
diagnosed with separation anxiety. 
Appl Anim Behav Sci 2014, 159: 
82–89.Author  Debra F . Horwitz
available onlineSeparation Anxiety Syndrome  (continued)

Canine and Feline, Seventh Edition  1235
SSepsis and Bacteremia
  BASICS
• Sepsis—life-threatening organ dysfunction 
caused by dysregulated host response to severe 
infection. • Bacteremia—presence of viable 
bacterial organisms in the bloodstream. 
• Terms are not synonymous, although often 
used interchangeably.
• With severe infection, immune system is 
stimulated by pathogen-associated products 
such as lipopolysaccharide (LPS) (Gram-
negative bacteria); lipoteichoic acid, 
peptidoglycan, bacterial DNA, exotoxins 
(Gram-positive bacteria); fungal cell walls; 
flagellin (protozoans). • Macrophage-derived 
cytokines activate and recruit neutrophils and 
other inflammatory cells, activate coagulation 
cascade, increase capillary permeability. 
• Activation of inducible nitric oxide synthase 
(iNOS) produces large quantities of nitric 
oxide, causing diffuse, profound vasodilation; 
refractory hypotension or vasodilatory shock 
may result. • White blood cells (WBCs) and 
platelets at sites of inflammation activate 
coagulation, produce thrombin, and activate 
platelets; anticoagulant and fibrinolytic 
pathways inhibited. Procoagulant state favors 
microthrombi that can lead to decreased 
tissue oxygen delivery, multiple organ 
dysfunction, and organ failure. Progression 
to a hypocoagulable state can occur. • Cryptic 
shock—decreased microcirculatory perfusion 
despite normal global hemodynamic parameters; 
results from decreased functional capillary 
density. • Endothelial cell dysfunction—
disruption of endothelial glycocalyx, changes 
in deformability of red blood cells (RBCs), 
WBC activation, microthrombosis, loss of 
vascular smooth muscle autoregulation, 
changes in capillary permeability. • Cytopathic 
hypoxia—sepsis-induced mitochondrial 
dysfunction renders cells unable to use 
oxygen to make ATP . • Bacteremia—may be 
transient and subclinical or escalate to overt 
sepsis when immune system overwhelmed; 
generally of more pathologic significance when 
source is venous or lymphatic drainage sites.
• Cardiovascular—increased or decreased 
cardiac output, decreased systemic vascular 
resistance, and increased vascular permeability. 
• Hemic/lymphatic/immune—procoagulant 
state favors formation of microthrombi, may 
progress to hypocoagulable state (consumption). 
• Endocrine—relative adrenal insufficiency 
(critical illness-related corticosteroid insufficiency 
[CIRCI]). • Respiratory. • Gastrointestinal. 
• Hepatobiliary. • Renal. • All systems can be 
affected by sepsis via systemic inflammatory response syndrome and multiple organ 
dysfunction syndrome.
Species
• Dog and cat. • No age, sex, or breed 
predispositions. • Large-breed male dogs—
predisposed to bacterial endocarditis, 
discospondylitis.
SIGNS
• May be acute or occur in vague or episodic 
fashion. • May involve single or multiple 
organ systems.
Historical findings variable depend on 
• Signs of sepsis vary with stage. • Dog: 
◦ Early sepsis—hyperdynamic state: 
tachycardia, bounding pulses, rapid capillary 
refill time, red mucous membranes, fever. 
◦ Late sepsis—thready pulses, prolonged 
capillary refill time, pale mucous membranes, 
cool extremities, stupor, hypothermia. • Cat: 
◦ Lethargy, pale mucous membranes, 
tachypnea, weak pulses, hypotension, hypo -
thermia, icterus, diffuse abdominal pain (even 
in absence of primary abdominal problem). 
◦ May present with tachycardia or a relative 
bradycardia (heart rate inappropriately low 
given illness, e.g., 120–150 bpm). • Specific 
clinical signs relate to site of infection or 
secondary organ dysfunction: ◦ Lameness. 
◦ Heart murmur—diastolic murmur may 
indicate aortic valve endocarditis. 
◦ Abdominal pain, peritoneal effusion. 
◦ Dyspnea. ◦ Dysuria, prostatomegaly. 
◦ Neurologic deficits—primary deficit or 
secondary to hypoglycemia, hypotension.
CAUSES
• Infection from bacterial (most common), 
viral, protozoal, fungal, or parasitic 
organisms. • Specific causes include: 
◦ Cardiovascular—endocarditis. 
◦ Cutaneous—bite wounds, deep pyoderma, 
infected burns, surgical site infection, abscess. 
◦ Gastrointestinal—septic peritonitis, 
gastrointestinal perforation, translocation, 
gastroenteritis, colitis. ◦ Genitourinary—
pyelonephritis, pyometra, prostatitis/prostatic 
abscess. ◦ Hemic/immune—blood-borne 
parasites, vector-borne infections. 
◦ Hepatobiliary—hepatitis, hepatic abscess, 
cholangitis, cholangiohepatitis. 
◦ Musculoskeletal—necrotizing fasciitis, 
osteomyelitis, septic arthritis. ◦ Neurologic—
discospondylitis. ◦ Respiratory—pneumonia, 
pyothorax. • Dogs: Gram-negative organisms 
(especially E. coli ) most common; 
polymicrobial infection reported in ~20% of 
dogs with positive blood cultures. • Cats—
bloodstream pathogens usually Gram-negative bacteria from Enterobacteriaceae  
family or obligate anaerobes; E. coli  and 
Salmonella  most common Gram-negative 
organisms cultured.
• Predisposing factors—hyperadrenocorticism, 
diabetes mellitus, liver or renal failure, splenec -
tomy, malignancy, burns. • Immunodeficient 
state—chemotherapy, feline leukemia virus or 
feline immunodeficiency virus infection, 
splenectomy, endogenous or exogenous 
corticosteroids. • IV catheters. • Indwelling 
urinary catheters or other drainage devices. 
• Surgical implants.
  DIAGNOSIS
• Other causes of fever, heart murmur, joint 
or back pain, or hypotension. • Clinical signs 
of chronic bacteremia may be similar to 
immune-mediated disease. • Other causes 
of distributive/vasodilatory shock—hypo -
adrenocorticism, anaphylaxis or mast cell 
tumor degranulation, antihypertensive drug 
overdose.
• Neutrophilic leukocytosis with a left shift 
and monocytosis. • Neutropenia may 
develop. • Hypoalbuminemia and a high 
alkaline phosphatase activity (2 times upper 
limit of normal)—~50% of affected dogs. 
• Hypoglycemia—~25% of affected dogs; 
hyperglycemia or hypoglycemia in cats. 
• Blood lactate concentration—persistent 
lactate elevation despite therapy portends 
poor prognosis.
• Aerobic and anaerobic cultures of site of 
infection—recommended but should not delay 
timely antibiotic therapy . • Suspected catheter-
induced sepsis—culture catheter tip. • Urine 
culture—urinary tract may be primary or 
secondary source of infection. 
• Endocarditis—consider Bartonella  testing 
(see Bartonellosis). • PCR, serology for 
tick-borne disease, as indicated. • PCR, 
serology or for organisms of interest, as 
indicated (e.g., Leptospira , influenza, Babesia ). 
• Fungal antigen testing. • Coagulation 
parameters should be monitored in most cases.
IMAGING
• Radiographs and ultrasound—may identify 
source of sepsis (e.g., pyometra, pneumonia) 
or secondarily infected organs (e.g., 
discospondylitis). • Ultrasound may help 
guide fine-needle aspiration for cytology/
culture. • Echocardiography—for suspected 
endocarditis. • CT, MRI—may identify some 
sources of sepsis or for surgical planning.

1236  Blackwell’s Five-Minute Veterinary Consult  
• Abdominocentesis, thoracocentesis, 
fine-needle aspirate—for cytology, culture/
sensitivity of effusion, masses: 
◦ Neutrophilic or pyogranulomatous 
inflammation, eosinophilic. ◦ Diagnostic 
peritoneal lavage if strong suspicion for 
abdominal sepsis without effusion. 
• Endo- or transtracheal wash, broncho -
alveolar lavage—samples for cytology, 
culture/sensitivity, PCR. • Fecal cytology, 
fecal PCR. • Blood cultures—in any patient 
that develops fever (or hypothermia), 
leukocytosis (especially with a left shift), 
neutropenia, shifting leg lameness, recent 
onset or changing heart murmur, or any 
sign of sepsis for which the source cannot 
be identified.
  TREATMENT
• Success requires early identification of the 
problem and aggressive intervention; careful 
monitoring is essential, patient status may 
change rapidly. • Start IV antibiotics within 1 
hour of identifying sepsis or septic shock . • Fluid 
therapy—IV bolus isotonic replacement 
crystalloids (cat, 10–15 mL/kg; dog, 20–30 
mL/kg), repeat as necessary; then administer 
crystalloids to provide maintenance needs, 
replace dehydration deficits and meet 
ongoing losses; provide albumin and plasma 
for hypoalbuminemia and coagulation 
abnormalities, respectively; consider synthetic 
colloids if clinical hypoproteinemia and 
hypotension are ongoing and biologic colloid 
sources unavailable. • Add dextrose to IV 
fluids if hypoglycemic. • Electrolytes and 
acid–base balance—correct abnormalities. 
• Pressor, inotrope therapy for persistent 
hypotension; refer early. • Source control—
should be completed after patient is 
normotensive and stable; provide appropriate 
wound care, bandage changes, or surgical 
intervention, as indicated.
• Goals—systolic blood pressure >90 
mmHg, heart rate 80–140 bpm (dogs) and 
160–225 bpm (cats), capillary refill time 1.5 
seconds, urine output >1–2 mL/kg/h, blood 
lactate <2.5 mmol/L in dogs. • Inadequate 
response to therapy prompts vasopressor 
administration (norepinephrine, dopamine, 
vasopressin). Most commonly recommended vasopressor is norepinephrine. Dopamine 
may be a good choice for cats with relative 
bradycardia. • As appropriate for each 
patient’s situation.
DIET
Nutritional support—provide by assisted 
feeding or feeding tube.
Prognosis should be discussed with client.
Any identifiable focus of infection such as an 
abscess should be located and removed where 
possible.
• IV antibiotics should be started within 
1 hour  of recognizing sepsis, septic shock. 
• Pending culture and sensitivity results, treat 
for organisms commonly isolated from 
presumed source of infection, or empirically 
cover Gram-positive, Gram-negative, aerobic, 
anaerobic organisms: ◦ Initial therapy—
clindamycin); anaerobes (metronidazole). 
◦ Enrofloxacin 10–15 mg/kg IV q24h (dogs); 
5 mg/kg/day IV (cats). ◦ Amikacin 10–15 
IV q8–12h. • De-escalate (reduce 
unnecessary antibiotics) once sensitivity 
results are available. • For many bacterial  
infections, total duration of therapy can be 
limited to 7–10 days; longer if source cannot 
be eliminated/drained or immune deficiencies 
Physiologic  doses (e.g., 0.25 mg/kg prednisone 
or 0.05 mg/kg of dexamethasone) may be 
indicated if patient has persistent hypotension 
unresponsive to fluid therapy and 
catecholamines.
NSAIDs—high risk of renal failure (acute 
kidney injury) or gastrointestinal ulceration 
in patient with sepsis/septic shock.
Aminoglycosides—use with caution in 
patient with renal impairment.  FOLLOW-UP
• Aminoglycoside therapy—monitor renal 
function. • Blood pressure, ECG, electrolytes, 
blood lactate.
Multiple organ failure.
Sepsis has a mortality rate of ~50%, with higher 
mortality for animals with multiorgan failure.
• Discospondylitis (dogs)— screen for 
Brucella  spp. • See Risk Factors.
SYNONYMS
• Septic shock. • Septicemia.
SEE ALSO
• Abscessation.
• CIRCI = critical illness-related 
corticosteroid insufficiency.
• iNOS = inducible nitric oxide synthase.
drug.
• RBCs = red blood cells.
• WBCs = white blood cells.
Burkitt JM, Haskins SC, Nelson RW, et al. 
Relative adrenal insufficiency in dogs with 
sepsis. J Vet Intern Med 2007, 21:226–231.
Rhodes A, Evans LE, Alhazzani W, et al. 
Surviving Sepsis Campaign: International 
guidelines for management of sepsis and 
septic shock: 2016. Crit Care Med 2017, 
45(3):486–552.
Author  Amie Koenig
Sharon Fooshee Grace.
available onlineSepsis and Bacteremia  (continued)

Canine and Feline, Seventh Edition  1237
SSertoli Cell Tumor
  BASICS
OVERVIEW
from the sustenacular cells of Sertoli.
• 8–33% of all testicular tumors in dogs, 
SIGNS
• Usually none. Fertility issues in breeding 
dogs.
• >50% of dogs will have hyperestrogenism. 
Most common clinical signs include: bilateral 
symmetric alopecia and hyperpigmentation, 
pendulous prepuce, gynecomastia, galactor-
rhea, atrophy of the penis, squamous 
metaplasia of the prostate.
• Clinical signs associated with severe 
pancytopenia include weakness, hemorrhage, 
and febrile episodes.
• Abdominal mass—if patient is cryptorchid.
• Cryptorchid testicles 12.7 per 1000 
dog-years (vs. 0 for scrotally located testicles).
• Cryptorchid and ≥6 years of age, 68.1 per 
1000 dog-years.
  DIAGNOSIS
• Interstitial cell tumor.
• More likely to have an abdominal location 
than other testicular tumors; high testicular 
temperature in the abdominal location may 
destroy spermatogenic cells and leave Sertoli 
cells unregulated.
T ransient neutrophilia followed by progressive 
neutropenia, thrombocytopenia, and 
Low testosterone-to-estradiol ratio.
IMAGING
Testicular and abdominal sonography to aid 
in differential diagnosis and identify retained 
testicles and comorbidities.DIAGNOSTIC PROCEDURES
• Histopathologic examination of testicular 
mass.
identify cell of origin.
• Serum anti-müllerian hormone may 
differentiate testicular tumors.
  TREATMENT
• Bilateral orchiectomy is the treatment of 
choice.
• Supportive care for dogs with bone marrow 
N/A
  FOLLOW-UP
• Recurrence of feminization may be 
• Serum hormone levels may be correlated 
with resolution of clinical signs.
Irreversible bone marrow ablation resulting in 
life-threatening hemorrhage and recurrent 
• Good in most patients.
• Guarded if cytopenias exist at diagnosis.
• Poor prognosis if aplastic anemia present.
• Clinical signs of hyperestrogenism expected 
to resolve within 1–3 months following 
castration; however, bone marrow hypoplasia 
might be irreversible.
• 50% of dogs with Sertoli cell tumor 
associated with hyperestrogenism and 
feminization.
• Hyperestrogenism can cause hematopoietic 
failure.
SEE ALSO
Hyperestrogenism (Estrogen Toxicity).
Canine testicular tumours: a study on 232 dogs. J Comp Pathol 2008, 
138(2–3):86–89.
557–571.

1238  Blackwell’s Five-Minute Veterinary Consult  
SSexual Development Disorders
  BASICS
• Errors in the establishment of chromosomal, 
gonadal, or phenotypic sex causing abnormal 
sexual differentiation. • Varies from 
ambiguous genitalia to apparently normal 
genitalia with sterility.
• Sexual differentiation is a sequential 
process—chromosomal sex established at 
fertilization (dog: 78,XX or 78,XY; cat: 
38,XX or 38,XY), development of gonadal 
sex, and finally development of phenotypic 
sex.  • Testis differentiation normally 
determined by sex chromosome constitution; 
SRY (on the Y chromosome) and SOX9  
(autosomal gene), expressed by Sertoli cells, 
are critical for testis differentiation. • Ovarian 
differentiation—an active process involving 
WNT4/RSPO1  and β-catenin. • Phenotypic 
sex differentiation (tubular reproductive tract 
and external genitalia) depends on gonadal 
sex—basic embryonic plan is female; male 
phenotype results if testes are capable of 
secreting anti-Müllerian hormone and 
testosterone at the correct time during 
embryogenesis, and functional androgen 
receptors (X-linked gene) are present on 
genital tissues. • Consensus terminology for 
categorizing disorders of sexual development 
(DSD) recently revised. Previous 
nomenclature also noted.
Sex Chromosome DSD
• Defects in number or structure of sex 
chromosomes—chromosomal non-
disjunction during meiosis causes trisomy, 
monosomy; mitotic non-disjunction of a 
single zygote causes mosaicism; fusion of 
zygotes leads to chimerism. • XXY 
(Klinefelter) syndrome—79,XXY (dog); 
39,XXY (cat): hypoplastic testes; phenotypic 
male (normal to hypoplastic genitalia); sterile; 
some tortoiseshell male cats. • XO (T urner) 
syndrome—77,XO (dog); 37,XO (cat): 
dysgenetic ovaries; phenotypic female; 
infantile genitalia; sterile.  • XXX syndrome—
79,XXX (dog): hypoplastic ovaries; anestrus to 
irregular estrous cycles; female phenotype. 
• T rue hermaphrodite chimera—XX/XY or 
XX/XXY (dogs and cats): ovarian and 
testicular tissue; phenotypic sex depends on 
amount of testicular tissue. • XX/XY chimera 
with testes and XY/XY chimera with testes 
(dogs and cats)—vary from phenotypic female 
with abnormal genitalia to male with possible 
fertility; some tortoiseshell males.
XY DSD
Disorders of T esticular Development
• Complete or partial testicular dysgenesis—
SRY-positive 78,XY dog: genitalia incompletely masculinized (enlarged clitoris); 
testes undescended or perivulvar; Müllerian 
and Wolffian duct derivatives variably 
present. • Ovotesticular DSD—XY sex 
reversal, true hermaphrodite.
Disorders in Androgen Synthesis or Action
• Complete androgen insensitivity 
syndrome—38,XY cat: testes at caudal pole 
of kidneys; no Wolffian or Müllerian duct 
derivatives; blind-ended vagina; vulva. 
• Partial androgen insensitivity syndrome—
78,XY dog: vulva; perivulvar scrotal-like 
swellings at 6 months of age; blind vaginal 
pouch; hypoplastic testes; epididymides, 
partially developed vasa deferentia; 
vulvar fibroblasts unable to bind dihydro -
testosterone. • Persistent Müllerian duct 
syndrome (male pseudohermaphrodite)—  
XY (dogs and cats): testes (50% are 
unilateral or bilateral cryptorchid); 
epididymides, vasa deferentia, prostate, 
oviducts, uterus, cervix, cranial vagina; 
penis, prepuce, and scrotum usually normal. 
• Isolated hypospadias—incomplete 
masculinization of urogenital sinus during 
urethral development causing abnormal 
location of urinary orifice from glans penis 
(mild) to perineum (severe); external 
genitalia unambiguous; testes (cryptorchid 
or scrotal) or bifid scrotum (cats) with 
XX DSD
Ovoteseticular DSD and T esticular DSD
• Canine XX DSD (sex reversal)— SRY-
negative 78,XX reported in 28 dog breeds, 
not in cats: autosomal gene causing testis 
induction presently unknown; two 
phenotypes: ◦ Ovotesticular DSD, XX true 
hermaphrodite (90% of cases)—ovotestis (at 
least one); masculinized female phenotype; 
varies from normal to abnormal vulva, 
normal or enlarged clitoris (os clitoris 
possible), uterus, oviducts, epididymides, and 
vasa deferentia; rarely fertile. ◦ Testicular 
DSD, XX males (10% of cases)—testes 
(usually cryptorchid); epididymides, vasa 
deferentia, prostate; bicornuate uterus, no 
oviducts; hypoplastic penis and prepuce; 
hypospadias common.
Androgen Excess
• Fetal origin—single report of congenital 
adrenal hyperplasia in a phenotypic male 
cat (38,XX, ovaries, oviducts, epididymides, 
vasa deferentia, bicornuate uterus) due to 
11 β-hydroxylase deficiency. • Maternal 
origin (female pseudohermaphrodite)—
XX; ovaries; masculinized genitalia (mild 
clitoral enlargement to nearly normal 
male genitalia); oviducts, uterus, cranial 
vagina; prostate variable; caused by 
exogenous sex steroid administration 
(progestegen oversupplementation) during 
pregnancy.SYSTEMS AFFECTED
• Reproductive—anomalies of the gonads, 
tubular tract, and external genitalia. • Renal/
urologic—occasionally affected (e.g., agenesis, 
incontinence, hematuria, cystitis).  • Skin/
exocrine—perivulvar dermatitis (hypoplastic 
vulva); perineal or peri-preputial dermatitis 
(hypospadias); hyperpigmentation (Sertoli 
cell tumor).
GENETICS
• Chromosomal sex abnormalities—usually 
caused by random events during gamete 
formation or early embryonic development. 
• XX DSD—autosomal recessive trait in 
American cocker spaniels and likely in 
beagles, German shorthaired pointers; familial 
in English cocker spaniels, pugs, Kerry blue 
terriers, Norwegian elkhounds, Weimaraners; 
other reported breeds include soft-coated 
wheaten terriers, vizslas, Walker hounds, 
Doberman pinschers, basset hounds, American 
pit bull terriers, border collies, Afghan 
hounds.  • Persistent Müllerian duct syndrome 
(PMDS)—autosomal recessive trait in 
miniature schnauzers in the United States, 
bassett hounds in the Netherlands, and 
possibly Persian cats; expression limited to XY 
individuals. • Hypospadias familial in Boston 
terriers. • Failure of androgen-dependent 
masculinization (predominantly cats) 
probably X-linked.
• Generally rare. • In affected breeds—may 
be common within families or within the 
breed as a whole.
Species
All are congenital disorders, but individuals 
with normal external genitalia may not be 
identified until breeding age or at routine 
gonadectomy.
Phenotypic females and males.
SIGNS
• Depends on type of disorder.  • Listed are 
possible findings for any of the conditions; 
not all occur with each specific disorder.
• Failure to cycle. • Infertility and sterility.
• Vulva, clitoris, prepuce, or penis—
abnormal size, shape, or location. • Urine 
stream—abnormal location. • Affected 
phenotypic males attractive to other males. 
• Urinary incontinence. • Vulvar discharge.

Canine and Feline, Seventh Edition  1239
SPhysical Examination Findings
• Vulva normal or hypoplastic. • Clitoris 
normal or enlarged; os clitoris. • Perivulvar 
dermatitis and vulvar discharge. • Testes 
scrotal, unilateral or bilateral cryptorchid; 
bifid scrotum. • Penis and prepuce normal or 
hypoplastic. • Urethral meatus normal or 
abnormal location. • Dermatologic signs of 
hyperestrogenism in males. • Abdominal 
mass.
CAUSES
• Congenital—heritable or nonheritable. 
• Exogenous steroid hormone administration 
during gestation.
Androgen or progestagen administration during 
pregnancy (female pseudohermaphrodite).
  DIAGNOSIS
Individuals with Unambiguous Genitalia
• Female infertility—male infertility, 
mistimed breeding, subclinical cystic 
endometrial hyperplasia/endometritis, 
hypothyroidism. • Failure to cycle (female)—
silent heat, hypothyroidism, hypercorticism, 
previous gonadectomy. • Male infertility—
female infertility, mistimed breeding, 
exogenous drug use affecting fertility, orchitis 
or epididymitis, testicular degeneration or 
hypoplasia, prostatitis.
• Usually normal. • Neutrophilia, normo -
chromic, normocytic anemia; hyperglo -
bulinemia, hyperproteinemia, azotemia are 
possible. • Urinalysis—may reveal cystitis 
with anatomic abnormalities that affect the 
location of the urethral meatus.
• Serum concentrations of sex steroid 
hormones (progesterone, testosterone, and 
estradiol)—generally below the normal range; 
may be normal if disorder mild and patient 
not sterile. • Detect testicular tissue— 
gonadotropin-releasing hormone (GnRH) or 
human chorionic gonadotropin (hCG) 
simulation test; resting serum anti-Müllerian 
hormone (AMH; see Cryptorchidism). 
• Karyotyping—to define chromosomal sex 
(Molecular Cytogenetics Laboratory, Texas 
A&M University).IMAGING
• Routine radiography and 
ultrasonography—may be of diagnostic value 
for suspected abdominal mass (e.g., testicular 
neoplasia with PMDS, testicular feminization, 
or XX DSD); males with signs referable to 
pyometra (female pseudohermaphrodite or 
PMDS). • Contrast studies (lower urogenital 
tract)—may be useful in diagnosing female 
Gross
Precisely describe the genitalia—size and 
location of the vulva or prepuce; presence and 
appearance of the clitoris, penis, scrotum, 
prostate, caudal vagina, or os clitoris; position 
of the urinary orifice (identifies the phallic 
structure as penis or clitoris).
• Examination of all tissues removed—to 
define the type of disorder. • Gonads—vary 
from nearly normal architecture to dysgenic 
or a combination of ovary and testis 
(ovotestis). • Essential to describe the 
components of the Müllerian and/or Wolffian 
duct system, if found.
  TREATMENT
• Usually outpatient. • Inpatient—if 
exploratory laparotomy.
Phenotypic females with a hypoplastic vulva 
and perivulvar dermatitis and males with 
hypospadias—local therapy to improve 
dermatologic sequelae (see Dermatoses, 
Erosive or Ulcerative).
• Most patients with no identified 
chromosomal abnormalities—exploratory 
laparotomy to determine the location 
and morphology of the gonads and 
internal genitalia. • Gonadectomy and 
hysterectomy (if a uterus is found)—
recommended. • Amputation of an 
enlarged clitoris—recommended if the 
mucosal surface is repeatedly traumatized. 
• Reconstructive surgery of the prepuce 
and malformed penis—dogs; may be 
necessary with testicular DSD, XX males, 
or hypospadias.  MEDICATIONS
Avoid androgen or progestagen use during 
  FOLLOW-UP
Sterilize individuals with heritable disorders.
• Infertility. • Sterility. • Urinary tract 
problems—incontinence; cystitis. • Testicular 
neoplasia. • Pyometra.
Patients not diagnosed at an early age—
pyometra (e.g., PMDS; female 
pseudohermaphrodite); testicular neoplasia 
(e.g., PMDS; any DSD with cryptorchidism).
SYNONYMS
• Hermaphrodites. • Intersexes. • Klinefelter 
syndrome. • Pseudohermaphrodites.  • Sex 
reversal. • T urner syndrome.
SEE ALSO
• Cryptorchidism.
• AMH = anti-Müllerian hormone.
• DSD = disorders of sexual development.
• GnRH = gonadotropin-releasing  
hormone.
• PMDS = persistent Müllerian duct 
syndrome.
Christensen BW. Disorders of sexual 
development in dogs and cats. Vet Clin 
Small Anim 2012, 42:515–526.
Author  Erin E. Runcan
acknowledges the prior contribution of Sara 
K. Lyle.(continued)  Sexual Development Disorders

1240  Blackwell’s Five-Minute Veterinary Consult  
SShaker/Tremor Syndrome, Corticosteroid Responsive
  BASICS
OVERVIEW
Fine, rapid, whole-body tremor.
Nervous
• Primarily dogs, but similar syndrome 
recently reported in 2 cats.
• Small to medium-size breed (<15 kg), 
young adult dogs (<5 years), regardless of coat 
color.
• Dogs with white-hair coats (e.g., Maltese 
and West Highland white terriers) historically 
have been overrepresented.
• Both sexes affected.
SIGNS
• Acute-onset, fine, rapid whole-body 
tremors.
• Clinical signs initially can be confused with 
signs of apprehension or hypothermia.
• Less commonly, signs can include abnormal 
nystagmus, hypermetria, head tilt, menace 
response deficits, and opsoclonus.
Most often associated with mild inflammatory 
  DIAGNOSIS
• Toxin ingestion—mycotoxins (penitrem A, 
roquefortine); metaldehyde (snail bait); 
pyrethrins/pyrethroids; organophosphates, 
many others.
• Hypomyelination—seen in puppies; chow 
chow, springer spaniel, Samoyed, Weimaraner, 
and Dalmatian.
• Metabolic disorder—hypoglycemia, 
hypoadrenocorticism, hypocalcemia, 
magnesium imbalance.
• Behavioral—fear.
IMAGING
N/A
Cerebellomedullary cistern CSF analysis—
mild mononuclear pleocytosis; CSF can be 
normal.  TREATMENT
• Prednisolone or prednisone (1–2 mg/kg PO 
q12h) for the first 1–2 weeks.
• Depending on clinical response, taper 
dosage slowly (usually over 4–6 months); 
assess periodically for clinical deterioration; if 
dosage reduced too rapidly, clinical signs may 
recur, necessitating reintroduction of initial 
dosage.
• Many patients do not require further 
Corticosteroids—may be contraindicated 
with infectious encephalitis.
  FOLLOW-UP
Weekly evaluations for approximately 
1 month; then monthly until corticosteroids 
are discontinued.
• Clinical signs usually subside in 3–7 days 
from onset of steroid treatment.
• In some patients, recurrence necessitates 
reinstitution of corticosteroids.
• A small percentage of patients require 
every-other-day, low-dose corticosteroids, 
indefinitely, to maintain remission.
SYNONYMS
• Idiopathic cerebellitis.
• White shaker syndrome.
• Idiopathic generalized tremor syndrome.
SEE ALSO
• Movement Disorders.
• T remors.
N/A Suggested Reading
Bagley RS, Kornegay JN, Wheeler SJ, et al. 
Generalized tremors in Maltese terriers: 
clinical findings in seven cases. J Am Anim 
Hosp Assoc 1993, 29:141–145.
Dewey CW. A Practical Guide to Canine & 
Feline Neurology, 2nd ed. Ames, IA: 
Wiley-Blackwell, 2008, pp. 311–322.
Wagner SO, Podell M, Fenner WR. 
Generalized tremors in dogs: 24 cases 
(1984–1995). J Am Vet Med Assoc 1997, 
211:731–735.
Author  Philip Schissler

Canine and Feline, Seventh Edition  1241
SShock, Cardiogenic
  BASICS
• Severe manifestation of forward heart failure 
in which patients have both clinical and 
biochemical evidence of inadequate tissue 
perfusion. • Profound impairment of cardiac 
function resulting in poor cardiac output and 
life-threatening end-organ hypoperfusion and 
hypoxia in the presence of adequate intra -
vascular volume and systemic vascular resistance. 
• Cardiac impairment may result from systolic 
dysfunction (dilated cardiomyopathy, sepsis, 
myocarditis, ischemia), diastolic dysfunction 
(hypertrophic cardiomyopathy, restrictive 
cardiomyopathy, tension pneumothorax/
mediastinum, restrictive pericarditis, pericardial 
tamponade), conduction defects and 
arrhythmias, valvular diseases, obstructive 
diseases, pulmonary thromboembolism, and 
structural defects. Understanding the 
underlying defect and its hemodynamic 
consequences is imperative to institute 
appropriate therapy. • In congestive heart 
failure (CHF), sometimes referred to as 
backward heart failure, the ventricle cannot 
adequately pump out the returning blood, 
resulting in systemic and/or pulmonary edema. 
This is in contrast to forward heart failure, 
when the heart is not pumping enough blood 
out to meet the needs of the body. Most, but 
not all, veterinary patients that present in 
cardiogenic shock will have concurrent CHF .
• Decreased cardiac output leads to 
hypotension and systemic hypoperfusion. 
• Hypotension decreases coronary perfusion, 
resulting in ischemia that provokes further 
myocardial dysfunction. • Peripheral 
vasoconstriction increases myocardial work 
and exacerbates tissue ischemia and energy 
depletion, resulting in organ dysfunction.
• Cardiovascular—cardiac dysfunction is 
causative, myocardial ischemia exacerbates 
cardiac dysfunction. • Musculoskeletal—
weakness. • Nervous—altered mental status. 
• Respiratory—as cardiac dysfunction 
progresses and atrial pressure increases, 
pulmonary edema and/or pleural effusion 
develop and hypoxemia ensues. • Endocrine—
hyperglycemia and insulin resistance. 
• Gastrointestinal—mucosal necrosis and 
sloughing, hemorrhage, bacterial translocation. 
• Hepatobiliary—hepatocellular enzyme 
leakage, cholestasis, reduced clearance of 
bacteria and bacterial by-products, and 
abnormal synthetic function; hepatic congestion 
may result from right-sided CHF . • Renal—
ischemic tubular damage, oliguria, development 
of acute kidney injury. • Hemic—homeostatic 
imbalances lead to microvascular thrombosis.GENETICS
Many breeds are predisposed to specific 
cardiac diseases.
Unknown
Unknown
• Dog and cat. • Any breed, age, or sex.
SIGNS
• Cardiac decompensation may be associated 
with a history of previously compensated heart 
disease and cardiac drug administration. • A 
suspicion of previously undiagnosed cardiac 
disease may result from a history of coughing, 
exercise intolerance, weakness, or syncope.
• Markers of poor perfusion: ◦ Weakness. 
◦ Altered mental status. ◦ Cool extremities 
and hypothermia. ◦ Pale mucous membranes. 
◦ Prolonged capillary refill time. ◦ Weak 
femoral pulse quality. ◦ Oliguria. • Muffled 
heart sounds if pericardial or pleural effusion 
is present. • Variable heart rate with possible 
cardiac arrhythmia, murmur or gallop sound. 
• Variable respiratory rate with possible 
increased bronchovesicular sounds, crackles, 
or moist cough.
CAUSES
Primary Cardiac Disease
• All cardiomyopathies (e.g., dilated, 
hypertrophic, unclassified, restrictive). 
• Severe mitral insufficiency or other 
end-stage valvular disease. • Chordae 
tendineae rupture. • Tachy- or brady -
arrhythmias. • Myocarditis. • Endomyocarditis 
(cats). • Structural defects (e.g. congenital 
heart disease).
Secondary Cardiac Dysfunction
• Cardiac tamponade. • Sepsis. • Severe 
electrolyte derangement. • Pulmonary 
thromboembolism. • Tension pneumothorax/
mediastinum. • Caval syndrome.
• Underlying cardiac disease. • Concurrent 
illness causing hypoxemia, acidosis, electrolyte 
imbalances, or as in sepsis, release of myocardial 
depressant factors.
  DIAGNOSIS
Cardiogenic shock is differentiated from 
other causes of circulatory shock when there 
is evidence of decreased cardiac output and 
tissue hypoxia in the face of adequate 
intravascular volume and systemic vascular 
resistance.CBC/BIOCHEMISTRY/URINALYSIS
CBC
Mature neutrophilia and lymphopenia 
secondary to stress.
Biochemistry Panel
• Hyperglycemia—stress. • Elevated anion 
gap—accumulation of lactic and renal acids. 
• Elevated hepatocellular enzyme activity—
hepatic hypoxia. • Elevated phosphorus—
decreased glomerular filtration rate (GFR). 
• Azotemia—decreased GFR or hypoxia 
induced renal injury. • Hyponatremia and mild 
hypoalbuminemia—suggestive of chronic CHF .
Isosthenuria—concomitant diuretic therapy 
or acute kidney injury.
• Blood gas analysis—metabolic acidosis, 
respiratory alkalosis or acidosis, hypoxemia, and 
evidence of increased tissue oxygen extraction 
(widened arteriovenous oxygen difference and/or 
decreased venous oxygen concentration in the 
absence of hypoxemia or anemia). 
• Hyperlactatemia—tissue hypoperfusion. 
• Increased cardiac troponin I levels—sensitive 
and specific marker of myocardial injury. 
• B-type natriuretic peptide (NT-proBNP)—
useful in ruling out intrinsic cardiac dysfunction.
IMAGING
Thoracic radiography may reveal cardiomegaly 
and evidence of CHF (pulmonary edema, 
pleural effusion).
Cageside Focused Pulmonary 
and Cardiac Ultrasound
• Lung ultrasound may reveal pleural effusion 
and/or B-lines (CHF). • Cardiac ultrasound 
to detect pericardial tamponade; patients with 
cardiogenic shock secondary to primary 
cardiac disease and some with secondary 
causes will have an increased left atrial size.
To characterize cardiomyopathy, valvular disease, 
myocardial contractility, structural disease, 
pericardial disease, and heartworm infection.
Thoraco-, abdomino-, and pericardiocentesis 
when indicated may elucidate underlying 
etiology.
Cardiac abnormalities consistent with various 
underlying etiologies; abnormalities 
consistent with tissue hypoxia and CHF .
  TREATMENT
Emergency inpatient intensive care 

1242  Blackwell’s Five-Minute Veterinary Consult  
SNURSING CARE
• Minimize stress—patients are extremely 
fragile and at risk of cardiac arrest. • Oxygen 
supplementation. • Pleural effusion—relieve 
with thoracocentesis. • Respiratory failure—
may require mechanical ventilation. • Patients 
should not receive any fluid therapy until the 
etiology of the underlying cardiac dysfunction 
is understood and cardiac function improved; 
exceptions include cardiogenic shock 
secondary to pericardial tamponade, tension 
pneumothorax and mediastinum, and 
pulmonary thromboembolism. • Pericardial 
tamponade—relieve with pericardiocentesis.
ACTIVITY
Minimize patient exertion.
DIET
Free choice access to water; withhold food 
until shock is resolved.
Discuss risk of imminent cardiac arrest and 
confirm “code status” in advance if possible.
• Bradyarrhythmia may require pacemaker 
implantation. • Tension pneumothorax may 
require thoracostomy tube placement or 
exploratory thoracotomy. • Caval syndrome 
secondary to Dirofilaria immitis  infection 
requires worm extraction.
• Fast-acting positive inotropes to improve 
cardiac function and preserve end-organ 
perfusion in patients with reduced myocardial 
contractility (pimobendan 0.25–0.3 mg/kg 
PO q12h in dogs and cats [IV formulation 
available in some countries]; dobutamine 
5–20 μg/kg/min CRI in dogs; 2.5–15 μg/kg/
min CRI in cats). While dobutamine can be 
used safely in many feline patients, seizures 
have been observed in some cats at doses 
exceeding 5 μg/kg/min. • Arrhythmias and 
conduction abnormalities should be corrected 
promptly with antiarrhythmic therapy, cardio  - 
version, or pacemaker implantation.
• Ventricular tachycardia: ◦ Dogs—lidocaine 
(2–4 mg/kg slow IV loading dose then 25–100 
μg/kg/min CRI) or procainamide (5–15 mg/kg 
slow IV loading dose then 25–50 μg/kg/min 
CRI). Due to many common adverse effects, 
amiodarone (2–5 mg/kg IV, infused over 
30–60 minutes) should only be used short term 
and the formulation should not contain 
polysorbate-80. • Sotalol (1–2.5 mg/kg PO, 
bid). Use with caution and at the lower end of 
the dosage range in dogs with concurrent CHF 
or DCM. ◦ Cat procainamide (1–2 mg/kg IV 
slowly over 20 minutes) or lidocaine (0.25–0.5 
mg/kg slow IV bolus then if needed 10–20 μg/
kg/min). Caution when using lidocaine in cats as they may be at higher risk of toxicosis. 
• Supraventricular tachyarrhythmia: 
◦ T reatments to slow the heart rate include 
vagal maneuvers, calcium channel blockers 
(diltiazem 0.125–0.35 mg/kg IV over 2–3 
minutes or 0.125–0.35 mg/kg/h CRI), 
beta-blockers (esmolol 0.5 mg/kg IV over 1 
minute), and procainamide (6–8 mg/kg IV 
over 5–10 minutes then 20–40 μg/kg/min 
CRI). ◦ Patients unresponsive to vagal 
maneuvers or emergency drug therapy may 
require DC cardioversion or overdrive pacing. 
• Bradyarrhythmia: ◦ Cardiac pacing. ◦ Some 
patients may benefit from atropine (0.02–0.04 
mg/kg IV) or isoproterenol (0.4 mg in 250 mL 
D5W slowly to effect). • Concurrent CHF: 
◦ Furosemide to treat pulmonary edema in 
dogs and cats (2–8 mg/kg IV or IM; or 0.5–1.0 
mg/kg/h CRI); IV route is preferable, but IM is 
appropriate when manual restraint to obtain IV 
access puts the patient at risk. ◦ Relief of pain 
or anxiety with morphine sulfate (0.1–0.5 mg/
kg/h IV CRI, or 0.2–2 mg/kg IM) can reduce 
excessive sympathetic activity and decrease 
oxygen demand, preload, and afterload.
• Avoid diuretic therapy in patients with 
pericardial tamponade, tension pneumothorax/
mediastinum, and pulmonary thrombo -
embolism. • Avoid beta-blockers and calcium 
channel blockers in patients with reduced 
myocardial contractility.
• Catecholamine infusions must be carefully 
titrated to maximize coronary perfusion with the 
least possible increase in myocardial oxygen 
demand. • Afterload reducers and vasodilators 
(angiotensin-converting enzyme inhibitors, 
nitroglycerin, and nitroprusside) should be used 
with caution because of the risk for worsening 
hypotension and decreasing coronary blood flow.
Dopamine may be used to improve systolic 
function as an alternative to dobutamine at a 
dose of 5–10 μg/kg/min (dogs and cats).
  FOLLOW-UP
• Serial assessment of perfusion (mentation, 
mucous membrane color, capillary refill time, 
pulse quality, muscle strength, temperature, 
serum lactate, urine output, heart rate, BP , 
and oxygenation indices), respiratory rate and 
effort, and pulmonary auscultation is required 
to optimize therapy. • Blood gas analysis and 
pulse oximetry to assess tissue oxygenation, 
ventilation, and acid–base balance. • Packed 
cell volume, serum total protein, serum 
electrolytes, hepatocellular enzymes, BUN, 
and serum creatinine to monitor effects of 
systemic tissue hypoxia. • Daily cardiac troponin I levels to assess degree of myocardial 
injury in some cases. • BP measurement may 
document hypotension. • Electrocardiography 
may aid detection and characterization of 
arrhythmias. • Pulse oximetry may document 
low oxygen saturation. • Central venous 
pressure monitoring may aid in assessment of 
cardiac preload and central venous oxygen 
saturation. • Hemodynamic monitoring to 
assess mixed venous oxygen saturation, cardiac 
output and systemic vascular resistance.
Prevention strategies aimed at the various 
underlying etiologies.
• CHF . • Cardiac arrhythmias. • Syncope. 
• Acid–base and electrolyte disturbances. 
• Renal dysfunction. • Cardiac arrest.
Dependent on underlying etiology. Patients 
with primary cardiac disease have generally 
worse prognosis (poor to grave) as compared 
to those with secondary cardiac dysfunction.
CHF
Variable, depending on underlying etiology.
None
Variable, depending on underling etiology.
SEE ALSO
• Atrioventricular Block. • Cardiomyopathy. 
• Endomyocardial Diseases—Cats. 
• Myocarditis. • Pericardial Disease. 
• Pneumothorax. • Pulmonary 
Thromboembolism. • Sepsis and Bacteremia. 
• Shock, Hypovolemic. • Shock, Septic. 
• Sick Sinus Syndrome. • Supraventricular 
Tachycardia. • Ventricular Tachycardia.
• BP = blood pressure.
De Laforcade A, Silverstein DC. Shock. In: 
Silverstein DC, Hopper K, ed., Small 
Louis, MO: Saunders, 2015, pp. 26–30.
Hopper K, Silverstein D, Bateman S. Shock 
syndromes. In: Dibartola SP , ed., Fluid Therapy 
in Small Animal Practice, 4th ed. Philadelphia, 
PA: Saunders, 2011, pp. 557–583.
Consulting Editor  Michael AherneShock, Cardiogenic  (continued)

Canine and Feline, Seventh Edition  1243
SShock, Hypovolemic
  BASICS
Inadequate circulating volume and perfusion 
due to fluid loss.
• Hemorrhage or other fluid loss results in a 
critical decrease in intravascular volume, 
diminished venous return, and decreased 
cardiac output.
• Compensatory neuroendocrine responses 
lead to peripheral vasoconstriction thus 
exacerbating tissue ischemia and energy 
• Cardiovascular—increased heart rate, 
increased cardiac contractility, and peripheral 
vasoconstriction; increased cardiac oxygen 
demand in the face of reduced oxygen 
delivery may cause arrhythmias.
• Respiratory—hyperventilation to 
compensate for metabolic acidosis.
• Musculoskeletal—weakness.
• Nervous—altered mental status.
• Endocrine—hyperglycemia and insulin 
• Gastrointestinal (GI)—mucosal necrosis 
and sloughing, hemorrhage, bacterial 
bacteria and their by-products, abnormal 
synthetic function.
• Renal—ischemic tubular damage, oliguria, 
acute kidney injury.
• Hemic—homeostatic imbalances lead to 
microvascular thrombosis as well as hyper- 
and hypocoagulability.
GENETICS
N/A
Unknown
N/A
• Any breed, age, or sex.
SIGNS
May have history of trauma, weakness, 
collapse, surgery, vomiting, diarrhea, 
decreased water intake, and polyuria.
• Compensated shock/warm shock/preshock:
 ◦Compensatory mechanisms may allow an 
otherwise healthy pet to be relatively 
asymptomatic despite a 10% reduction in 
total effective blood volume. When homeostatic mechanisms fail, decompen-
sated shock ensues.
• Decompensated shock:
 ◦Poor perfusion (pale mucous membranes 
[may be compounded by anemia], prolonged 
capillary refill time, weak peripheral pulses, 
weakness, altered mental status, hypother -
mia/cool extremities, oliguria).
 ◦Absent/minimal jugular vein distension.
 ◦Tachycardia ± arrhythmia.
 ◦Tachypnea.
 ◦Clinical dehydration (decreased skin 
turgor, tacky mucous membranes, and 
sunken eyes) more common in patients 
with fluid loss than hemorrhage.
CAUSES
• T rauma.
• Ruptured neoplasm.
• GI bleeding (e.g., ulcerative disease, 
neoplasia, severe thrombocytopenia).
• Coagulopathy (e.g., severe thrombocytopenia/
thrombocytopathy, von Willebrand factor 
deficiency, anticoagulant rodenticide 
intoxication, synthetic liver failure, 
 disseminated intravascular coagulation, 
hemophilia, other bleeding disorders).
Fluid Loss
• GI (vomiting and diarrhea).
• Urinary (renal failure, diabetes mellitus, 
diabetes insipidus, hypercalcemia, Addison’s, 
and Cushing’s diseases).
• Burns.
• Third spacing (any disease resulting in 
significant effusion).
No specific risk factors; caused by another 
  DIAGNOSIS
Hypovolemic shock differentiated from other 
causes of circulatory shock when inadequate 
circulating volume results in decreased cardiac 
output in the face of normal or increased 
cardiac function and normal or increased 
CBC
• Hematocrit and platelet count are variable 
(may be decreased with hemorrhage).
• Variable total protein (TP) and albumin 
(decreased with hemorrhage; increased in 
fluid loss).
• Elevated hepatocellular enzyme activity (alanine 
aminotransferase, aspartate aminotransferase).• Variable electrolyte derangements (more 
likely in fluid loss).
• Variable anion gap.
• Azotemia due to decreased glomerular 
filtration rate.
• Urine specific gravity may be increased; 
however, acute tubular injury due to renal 
hypoxia may cause isosthenuria.
• Blood gas analysis may reveal metabolic 
acidosis and evidence of increased tissue 
oxygen extraction (widened arteriovenous 
oxygen difference and/or decreased venous 
oxygen concentration in a patient without 
hypoxemia or anemia).
• Hyperlactatemia reflects decreased clearance 
and increased production of lactate.
• Coagulation testing if critically ill or if 
evidence of significant hemorrhage.
IMAGING
• Thoracic radiography may reveal 
microcardia and pulmonary vascular 
underperfusion.
• May have radiographic or ultrasonographic 
findings of pleural or abdominal effusion.
Thoracocentesis, abdominocentesis, or 
pericardiocentesis, if indicated, may provide 
insight into underlying etiology.
Consistent with tissue hypoxia and underlying 
etiology.
  TREATMENT
• Maximize blood oxygen content:
 ◦Assess and stabilize airway and breathing 
as necessary.
 ◦Supplemental oxygen and ventilatory 
support as needed.
 ◦Significant anemia (packed cell volume 
[PCV] <25–30%) in a hypovolemic patient 
is concerning and should be corrected.
• Control further fluid loss:
 ◦External bleeding controlled with direct 
pressure; internal bleeding may require 
• Control of fluid loss, other than hemorrhage, 
aimed at control of signs (e.g., antiemetics) and 
correcting underlying disorder.
• Fluid resuscitation:
 ◦Once IV or IO access obtained, initial 
fluid resuscitation performed with isotonic 
crystalloid such as lactated Ringer’s 
solution, normal saline, Plasmalyte-A, and

1244  Blackwell’s Five-Minute Veterinary Consult  
SNormosol-R (20–30 mL/kg, dog; 15–20 
mL/kg, cat; over 15 minutes). If no 
significant dehydration and no other 
contraindications, addition of 7.5% 
hypertonic saline (4 mL/kg over 15 
minutes) may expedite resuscitation.
 ◦Assess response to initial bolus. If vital 
signs and other resuscitation parameters 
return to normal, monitoring must be 
continued to ensure stability. If vital signs 
and other resuscitation parameters 
transiently improve or if little or no 
improvement seen, another crystalloid 
bolus should be infused and colloids such as 
hydroxyethylstarch (dose variable, 
dependent on type) or appropriate blood 
products (10–20 mL/kg) considered.
 ◦Process is repeated until resuscitation 
parameters normalize. When bolusing 
fluids to correct perfusion deficits, monitor 
not only for response to therapy, but also 
for potential complications.
 ◦While fluid boluses are used to correct 
perfusion deficits, hydration deficits must 
be corrected more slowly. After perfusion 
has normalized, patient is reassessed and 
fluid therapy targeted to correct hydration 
deficits over 12–24 hours.
• T raditional endpoints of resuscitation 
(restoration of normal vital signs, blood 
pressure, and urine output) remain the 
standard of care; however, it has been 
documented that critically ill patients have 
evidence of ongoing tissue hypoxia despite 
normalization of these parameters, suggesting 
occult oxygen debt and the presence of 
compensated shock. There is evidence that 
normalization of vital signs, blood lactate, 
base deficit, and oxygen transport indices 
such as cardiac index, oxygen delivery, oxygen 
consumption, and mixed venous oxygen and 
central venous oxygen saturation in concert 
are more sensitive markers for adequacy of 
tissue perfusion than any of these variables 
alone. Until stronger support exists for 
preferential selection of one endpoint over 
others, utilization of as many of these markers 
as are available seems advisable.
ACTIVITY
DIET
Withhold oral intake until shock is resolved.
Discuss risk of cardiac arrest and confirm 
“code status” in advance if possible.
Identify and repair source of fluid loss (most 
common in hemorrhage-induced).  MEDICATIONS
• For patients with refractory hypovolemic 
shock, rule out ongoing losses (especially if 
hemorrhage-induced); administer blood 
products as needed.
• If adequate circulating volume is assured 
and patient is still demonstrating clinical 
signs of shock (not very common with 
hypovolemic shock), consider:
 ◦Pressors such as dopamine (5–20 μg/kg/
min), norepinephrine (0.05–2 μg/kg/min), 
or vasopressin (0.5–2 mU/kg/min). These 
can be used for vasopressor support in dogs 
and cats. Monitor for tachyarrhythmia and 
excessive peripheral vasoconstriction.
 ◦Positive inotropes such as dobutamine 
(2–20 μg/kg/min) may be beneficial in 
patients with decreased contractility or 
myocardial depression. Monitor for 
tachyarrhythmia. While dobutamine can 
generally be used safely in dogs, seizures have 
been observed in some cats at doses 
exceeding 5 μg/kg/min.
• For bleeding dogs, antifibrinolytic medica -
tions such as ε-aminocaproic acid (50–100 
mg/kg IV or PO q6h) or tranexamic acid (10 
mg/kg IV bolus over 20 minutes, followed by 
10 mg/kg/h IV CRI for 3 hours, then 10 mg/
kg over 20 minutes q6h) may be considered.
N/A
N/A
N/A
N/A
  FOLLOW-UP
• Serial assessment of perfusion:
 ◦Physical exam including mentation, 
mucous membrane color, capillary refill 
time, pulse quality, muscle strength, 
temperature, and heart rate.
 ◦Hemodynamic monitoring to include 
arterial blood pressure (frequently reveals 
disproportionately low diastolic pressure), and 
in a subset of patients central venous pressure, 
cardiac output and tissue oxygenation.
 ◦Laboratory data including serum lactate and 
base deficit; patients with hemorrhage-induced hypovolemic shock should have minimum of 
daily PCV, and TP assessed more frequently.
• Serial assessment of respiratory rate and 
to optimize therapy.
• Urine output as indicator of glomerular 
filtration rate and renal blood flow.
• ECG may aid in characterization of 
• Minimum of daily PCV, serum TP , blood 
glucose, blood gas, serum electrolytes, 
hepatocellular enzymes, BUN, and serum 
creatinine to monitor effects of systemic 
tissue hypoxia and to guide clinical 
• Acid–base disturbances.
• Anemia and thrombocytopenia.
• Multiple organ dysfunction.
• Low colloid oncotic pressure.
• Volume overload with clinical signs of 
pulmonary and/or peripheral edema.
• Dilutional coagulopathy can occur in patients 
receiving very large resuscitation volumes (more 
than 1–2 blood volumes), due to dilution of 
clotting factors and proteins respectively, but is 
rare within the first hour of resuscitation. 
Coagulation times should be used to guide the 
administration of fresh frozen plasma.
Depends on underlying etiology and ability 
to institute appropriate therapy.
N/A
SEE ALSO
• Shock, Cardiogenic.
syndromes. In: Dibartola SP , ed., Fluid 
Therapy in Small Animal Practice, 4th ed. 
Philadelphia, PA: Saunders, 2011, 
pp. 557–583.
Consulting Editor  Michael AherneShock, Hypovolemic  (continued)

Canine and Feline, Seventh Edition  1245
SShock, Septic
  BASICS
Sepsis-induced hypotension, attributable to 
low systemic vascular resistance that persists 
despite adequate intravascular volume and 
• In sepsis, an elaborate interaction of 
inflammatory cells and mediators decreases 
systemic vascular resistance and provokes 
maldistribution of blood flow (distributive 
effect). Vasodilation is primarily mediated by 
increased nitric oxide and prostacyclin 
synthesis induced by endotoxin and 
inflammatory cytokine interaction with 
vascular endothelial cells. In the face of severe 
arterial vasodilation, cardiac output is 
insufficient to maintain tissue oxygen 
delivery. • Infectious agents trigger large-scale 
activation of monocytes, macrophages, and 
neutrophils that interact with endothelial 
cells, inducing a generalized inflammatory 
response. Endothelial injury is a universal 
feature, mediated by cellular and humoral 
factors that increase capillary permeability, 
and fluid shifts out of the intravascular space. 
Presence of interstitial edema and micro -
vascular sludging further compound oxygen 
delivery, and tissue hypoxia leads to organ 
failure and death.
• Cardiovascular—arterial vasodilation and 
maldistribution of blood flow with hypo -
tension predominates; cardiac output 
frequently normal or high; however, myo -
cardial dysfunction due to circulating factors 
can be important. • Nervous—altered mental 
status. • Endocrine—may have hyperglycemia 
and insulin resistance, or insufficient 
production of either corticosteroids or 
vasopressin. • Gastrointestinal—mucosal 
necrosis, hemorrhage, bacterial translocation. 
• Respiratory—interstitial and alveolar edema 
due to enhanced microvascular permeability; 
hypercoagulopathy may result in pulmonary 
thromboembolism.  • Hepatobiliary—
hepatocellular enzyme leakage, cholestasis, 
reduced bacterial clearance, hypoglycemia and 
abnormal synthesis. • Hemic—microvascular 
thrombosis, hyper- and hypocoagulopathy. 
GENETICS
N/A
Unknown
N/A
• Dog and cat. • Any breed, age, or sex.SIGNS
Recent infection, injury, serious illness, 
surgery, or immunosuppression.
• Dogs may have a hyperdynamic form, 
typified by altered mental status, weakness, 
hypotension, tachycardia, tachypnea, hyper -
emia, fast capillary refill time (CRT), 
bounding pulses, and fever. Cats rarely have 
hyperdynamic signs. • Patients with the 
hypodynamic form are more likely to exhibit 
altered mental status, weakness, hypotension, 
bradycardia, tachypnea, pale mucous 
membranes, prolonged CRT, weak pulses, 
and hypothermia.
CAUSES
• Septic peritonitis—ruptured viscus; 
penetrating wound. • Respiratory and pleural 
space—pneumonia, pyothorax. • Skin or soft 
tissue—wounds, burns, cellulitis, abscess. 
• Urinary tract—pyelonephritis. 
• Reproductive—prostatitis, metritis, 
pyometra. • Cardiovascular—endocarditis, 
bacteremia. • Musculoskeletal—septic 
arthritis, osteomyelitis.  • Iatrogenic—
catheters, implants, surgical sites. • CNS—
meningitis, encephalitis.
• Extremes of age. • Concurrent disease 
(e.g., diabetes mellitus, Cushing’s disease, 
malignancy). • Immunosuppression.  
• Surgery, trauma, burns. • Prior antibiotics.
  DIAGNOSIS
• Other causes of distributive shock (e.g., 
drug/toxin reaction, anaphylaxis, adrenal 
insufficiency). • Hypovolemic shock. 
• Cardiogenic shock. • Heatstroke.
• Neutrophilia or neutropenia, left shift, and 
toxic change. • Lymphopenia. 
• Thrombocytopenia. • Variable hematocrit 
and blood glucose. • Hypoalbuminemia. 
• Elevated bilirubin and liver enzyme activity. 
• Electrolyte derangements.  • Azotemia. 
• Isosthenuria and variably active urine 
sediment.
and prothrombin times, increased D-dimers 
and fibrin degradation products, and 
decreased levels of antithrombin and protein C. 
• Blood gases may reveal hypoxemia and 
acid–base disturbances. • Hyperlactatemia.  
• Cytology, Gram stain, and culture and 
sensitivity on samples obtained from potential 
sites of infection may reveal etiologic 
organisms. • Culture and sensitivity of urine and blood may be useful when the source of 
sepsis is unknown. • Adrenocorticotropic 
hormone (ACTH) stimulation test in patients 
unresponsive to standard therapy.
IMAGING
• Thoracic radiographs and CT may reveal 
septic focus or cause for respiratory 
dysfunction; may also provide insights into 
volume status.  • Echocardiography may 
document a vegetative valvular lesion and/or 
characterize cardiac function and volume 
status. • Abdominal ultrasonography and CT 
may detect source of infection.
When indicated, tissue aspirates, thoraco-, 
abdomino-, and arthrocentesis may provide 
Consistent with inflammation, tissue hypoxia, 
and underlying etiology.
  TREATMENT
management. Early surgical intervention 
when possible to control source of infection.
Maximize Blood Oxygen Content
• Assess and stabilize the airway and breathing 
as necessary.  • Administer supplemental 
oxygen and provide ventilatory support as 
needed.  • Significant anemia (packed cell 
volume [PCV] <25%) should be corrected.
Resuscitation
Most septic patients are hypovolemic and 
require initial fluid resuscitation with isotonic 
crystalloids such as lactated Ringer’s solution, 
normal saline, Plasmalyte-A, and Normosol-R 
(20–30 mL/kg, dog; 15–20 mL/kg, cat, over 
15 minutes). If no significant dehydration, 
addition of 7.5% hypertonic saline (4 mL/kg 
over 15 minutes) may expedite resuscitation:
• After the initial bolus, patient is reassessed. 
If vital signs and other resuscitation parameters 
normalize, continue monitoring to ensure 
stability. If vital signs and other resuscitation 
parameters transiently improve or if little or 
no improvement is seen and patient is still 
deemed hypovolemic, sequential crystalloid 
boluses should be infused and colloids (dose 
variable, dependent on type) may be 
considered.  • Septic patients receiving large 
fluid volumes may achieve adequate 
circulating volume without normalization of 
BP and other perfusion parameters. 
Continued aggressive fluid therapy in these 
patients will result in volume overload and 
vasopressors and/or positive inotropes are 
indicated. Monitor closely since infusion of 
large volumes may precipitate pulmonary

1246  Blackwell’s Five-Minute Veterinary Consult  
Sedema in patients with capillary leak. • IV 
fluids, vasopressors, and positive inotropes are 
titrated until resuscitation endpoints have 
been achieved. T raditional endpoints of 
resuscitation (restoration of normal vital 
signs, BP , and urine output) remain the 
occult oxygen debt and presence of 
base deficit, and oxygen transport indices are 
more sensitive markers for adequacy of tissue 
perfusion than any of these variables alone. 
Until stronger support exists for preferential 
selection of one endpoint over others, 
utilization of as many of these markers as are 
available seems advisable. • Blood products 
should be administered based on patient 
need. Packed red blood cells are administered 
to anemic patients to improve oxygen-
carrying capacity and plasma products are 
used to correct coagulation deficits.
ACTIVITY
DIET
Identify and eliminate infection source when, 
and as early as, possible.
• Once adequate circulating volume is 
achieved, improvement in systemic BP and 
other clinical resuscitation parameters may 
require one or more vasopressors and/or 
positive inotropes: ◦ Norepinephrine (0.05–2 
μg/kg/min), vasopressin (0.5–2 mU/kg/min), 
or dopamine (5–20 μg/kg/min) can be used 
for vasopressor support (dogs and cats). 
Monitor for tachyarrhythmia and excessive 
peripheral vasoconstriction. ◦ Dobutamine 
(2–20 μg/kg/min) is primarily used as a 
positive inotrope in canine septic shock 
myocardial depression. Monitor for tachy -
arrhythmia. While dobutamine can be used 
safely in many feline patients, seizures have 
been observed in some cats at doses exceeding 
5 μg/kg/min. • It is essential that IV, empiric, broad-spectrum antibiotic therapy be 
instituted early in septic patients; the 
spectrum should be narrowed when culture 
results become available. Empiric selection 
based on patient’s underlying immune status, 
suspected source and organism(s) responsible, 
specific antibiotic properties (tissue 
penetration, cidal versus static activity), and 
considerations for resistance (previous 
antibiotic use, hospital- or community-
acquired infection).  • It is not unreasonable 
to empirically treat patients not responding 
adequately to standard therapy with 0.75–1.0 
mg/kg q6h IV hydrocortisone after 
undergoing a standard ACTH stimulation 
test. Therapy should be continued in patients 
in whom relative adrenal insufficiency is 
N/A
N/A
N/A
N/A
  FOLLOW-UP
• Serial assessment of perfusion to optimize 
titration of fluids and vasoactive drugs: 
◦ Physical exam including mentation, 
mucous membrane color, CRT, pulse quality, 
muscle strength, temperature, and heart rate. 
◦ Hemodynamic monitoring to include 
arterial BP (frequently reveals disproportion-
ately low diastolic pressure), and in some 
patients central venous pressure, cardiac 
output, and tissue oxygenation.  ◦ Thoracic 
ultrasound to monitor for pulmonary changes 
and to aid in assessing patient volume status 
and cardiac systolic function. ◦ Laboratory 
data including serum lactate and base deficit. 
• Blood gas analysis and pulse oximetry to 
follow tissue oxygenation, ventilation, and 
acid–base status. • Serial assessment of 
respiratory rate and effort, and pulmonary 
auscultation. • Continuous ECG to detect 
arrhythmia. • Urine output as an indicator of 
glomerular filtration rate and renal blood 
flow. • Minimum of twice daily PCV, serum 
total protein, blood glucose, and serum 
electrolytes; once daily hepatocellular 
enzymes, blood urea nitrogen, and serum 
creatinine to monitor effects of systemic tissue 
hypoxia. Patients with coagulopathy should have coagulation indices, PCV and total 
protein assessed as needed.
• Timely and effective wound treatment.  
• Appropriate antimicrobial therapy.
• Volume overload. • Pulmonary edema.  
• Vasculitis and peripheral edema. • Acid–base 
disturbances. • Anemia. • Thrombocytopenia 
and other coagulopathy. • Multiple organ 
dysfunction. • Cardiac arrest.
Dependent on underlying etiology and ability 
Sepsis
N/A
Variable infectious agent etiologies have 
N/A
SYNONYMS
N/A
SEE ALSO
Syndrome)—Dogs. 
Animal Critical Care Medicine, 2nd ed., 
St. Louis, MO: Saunders, 2015, pp. 26–30.
Russell JA, Rush B, Boyd J. Pathophysiology 
of septic shock. Crit Care Clin 2018, 
34:43–61.
available onlineShock, Septic  (continued)

Canine and Feline, Seventh Edition  1247
SShoulder Joint, Ligament, and Tendon Conditions
  BASICS
These make up the majority of causes for 
lameness in the canine shoulder joint, 
excluding osteochondritis dissecans lesions.
Bicipital Tenosynovitis
• Strain injury to the tendon of the biceps 
brachii.
• Mechanism of injury—direct trauma; 
indirect trauma (more common).
• Pathologic changes—from partial 
disruption of the tendon to chronic inflamm­
atory changes, including dystrophic calcification.
• Proliferation of the fibrous connective tissue 
and adhesions between the tendon and the 
sheath—limit motion; cause pain.
Fibrotic Contracture of the Infraspinatus 
Muscle
• Primary muscle–tendon disorder—not a 
• Fibrous tissue replaces normal muscle.
• Loss of elasticity and function.
• Degeneration and atrophy of affected 
muscle.
• Partial muscle disruption—likely caused by 
repetitive strain injuries.
Medial Shoulder Instability
• Structural damage (stretch and rupture) of 
the capsulotendinous structures of the medial 
joint—the medial glenohumeral ligament, 
subscapularis tendon, and medial joint 
capsule.
• Likely secondary to repetitive strain injury—
overuse injury vs. altered shoulder mechanics 
due to concurrent ipsilateral elbow disease.
Other
• Rupture of the biceps brachii tendon of 
origin—strain injury or disruption of the 
tendinous fibers at or near the junction with 
the supraglenoid tubercle of the scapula.
• Mineralization of the supraspinatus tendon; 
granular deposits between the fibers of the 
tendon; unknown cause; probably repetitive 
strain injury.
• Avulsion or fracture of the insertion of the 
supraspinatus tendon—bone is avulsed from 
the greater tubercle of the proximal humerus.
• Strain injury to other muscles/tendons in 
the region.
Common cause of forelimb lameness.
Species
Medium ­ to large ­breed dogs.
• Skeletally mature dogs ≥1 year of age.
• Usually 3–7 years of age.
SIGNS
• Bicipital tenosynovitis—onset usually 
insidious; often of several months duration; 
may be a traumatic incident as the inciting 
cause; subtle, intermittent lameness that 
worsens with exercise.
origin—similar to bicipital tenosynovitis; may 
have acute onset due to a known traumatic 
event; usually subtle, chronic lameness that 
• Medial shoulder instability— onset usually 
• Mineralization of the supraspinatus 
tendon—onset usually insidious; chronic 
lameness that worsens with activity.
• Avulsion/fracture of the supraspinatus 
tendon—similar to mineralization of 
supraspinatus tendon.
• Fibrotic contracture of the infraspinatus 
muscle—usually sudden onset of lameness 
during a period of outdoor exercise (e.g., 
hunting); shoulder lameness and tenderness 
gradually disappears within 2 weeks; 
condition results in chronic, persistent 
lameness 3–4 weeks later, which is not 
particularly painful but has characteristic gait 
and limb carriage.
• Bicipital tenosynovitis—short and limited 
swing phase of gait owing to pain on 
extension and flexion of the shoulder; pain 
inconsistently demonstrated on manipulation 
of shoulder; pain most evident by applying 
deep digital pressure over the tendon in the 
intertubercular groove region while 
simultaneously flexing the shoulder and 
extending the elbow.
• Rupture of the biceps brachii tendon—
similar to above, however full rupture will 
result in exaggerated extension of the elbow 
with simultaneous flexion of the shoulder 
(when compared to the contralateral side).
• Medial shoulder instability—pain on 
abduction of the thoracic limb with excessive 
abduction when compared to the contralateral 
side. Under sedation, abnormal abduction 
angles have been measured to be approximately 
50 degrees, while normal abduction angles are 
approximately 30 degrees.
tendon—similar; manipulations often do not 
produce pain; may palpate firm swelling over 
the greater tubercle.• Avulsion or fracture of the supraspinatus 
tendon—similar to mineralization of the 
muscle—usually not painful on manipulation; 
not possible to internally rotate (pronate) the 
shoulder joint; when forced, the caudal aspect 
of the scapula elevates off the trunk, when 
standing—elbow adducted; paw abducted and 
outwardly rotated; when patient is walking—
lower limb swings in a lateral arc (circumduc ­
tion) as the paw is advanced; marked atrophy 
of the infraspinatus muscle on palpation.
CAUSES
• Indirect or direct trauma—likely.
• Repetitive strain injury (indirect trauma)—
• Overexertion and/or fatigue.
• Poor conditioning before performing 
athletic activities.
• Obesity.
  DIAGNOSIS
• Examination, palpation, and radiography 
that localizes disease to the shoulder will only 
be accurate 80% of the time—20% of the 
time, disease localized to the shoulder will 
actually be the result of elbow pathology/
dysplasia.
• Luxation or subluxation of the shoulder 
joint—history of trauma with an acute onset 
of lameness; often severe lameness with 
marked pain on manipulation of the shoulder 
joint.
• Osteosarcoma of the proximal humerus—
progressive lameness with varying degrees of 
pain on manipulation of the shoulder; may 
note swelling and tenderness of the proximal 
humerus.
• Brachial plexus nerve sheath tumor—slow, 
insidious, progressive lameness over a period 
of months; marked atrophy of the muscles 
with chronic disease; may feel a firm mass 
deep in the axillary region that is painful to 
digital pressure.
IMAGING
Radiology
• Required for differentiation.
• Craniocaudal and mediolateral views 
necessary for all patients.
• Skyline projections are helpful for 
highlighting the biceps groove.
Bicipital T enosynovitis
• Radiographs generally normal with recent 
injuries.
• Mediolateral view (chronic disease)—may 
see bony reaction on the supraglenoid tubercle,

1248  Blackwell’s Five-Minute Veterinary Consult  
Sdystrophic calcification of the bicipital tendon, 
sclerosis of the floor of the intertubercular 
groove, and osteophytes in the intertubercular 
groove (also in the skyline view).
Ruptured Origin of the Biceps Brachii 
T endon
Chronic disease—may see bony, irregular 
reaction on the supraglenoid tubercle.
Mineralization of the Supraspinatus 
T endon
• Mediolateral view—calcified foci in tendon 
cranial and immediately medial to the greater 
tubercle of the proximal humerus.
• Tangential or skyline view of the inter­
tubercular region of the proximal humerus—
eliminates superimposition; allows distinction 
from calcification of the biceps brachii tendon.
• Often bilateral radiographically but rarely 
produces bilateral lameness.
Avulsion/Fracture of the Supraspinatus 
T endon
• Similar to mineralization of the supra­
spinatus tendon.
• Avulsion fragment—may be seen as a defect 
in the greater tubercle of the humerus; 
generally not as radiographically dense as that 
identified with mineralization of the supra  ­ 
Muscle
Radiographically normal.
CT, Ultrasonography, and MRI
• May help identify muscle injuries, bicipital 
tenosynovitis, and rupture of the biceps 
brachii tendon of origin.
• Useful for determining the location of 
calcific densities near the intertubercular 
groove.
• MRI may be useful in evaluating medial 
shoulder disease, however extensive peer ­
reviewed publications are lacking.
identify intra ­articular disease; fluid should be 
straw ­colored with normal to decreased 
viscosity; cytologic evaluation: <10,000 
nucleated cells/ μL (>90% are mononuclear 
cells).
• Arthroscopic exploration of the shoulder 
joint—diagnose bicipital tenosynovitis and 
rupture of the biceps brachii tendon of 
origin; evaluate support structures of the 
medial shoulder, confirm lack of other 
intra­articular disease (osteochondrosis or 
traumatic injury).
• Bicipital tenosynovitis—mineralization of 
the biceps tendon; osteophytosis of the 
intertubercular groove; proliferative synovitis; 
impingement of the supraspinatus tendon of 
insertion on the biceps tendon, and fibrous adhesions between the biceps tendon and its 
synovial sheath; histologically, synovial 
proliferation, edema, fibrosis, dystrophic 
mineralization, and lymphocytic–plasmacytic 
infiltration of the tendon and synovium.
• Ruptured origin of the biceps brachii 
tendon—partial to complete rupture of the 
biceps tendon at its insertion on the supra  ­ 
glenoid tubercle, proliferative synovitis, and 
fibrous adhesions between the biceps tendon 
and its synovial sheath; histologically, synovial 
proliferation, edema, fibrosis, and occasional 
dystrophic mineralization.
• Medial shoulder instability—identify 
fraying, stretching or complete disruption of 
the medial glenohumeral ligament or the 
subscapularis tendon.
tendon—tendon often looks normal, but 
longitudinal incision reveals numerous 
pockets of mineralized debris within the 
fibers; histologically, chondromucinous 
stromal degeneration of the tendon with 
multiple foci of dystrophic mineralization.
• Avulsion of the supraspinatus tendon 
insertion—often looks normal, but longi­
tudinal incision reveals bone fragment(s) 
surrounded by a fibrous tissue capsule; usually 
see a corresponding bony defect in the greater 
tubercle.
  TREATMENT
• Overall, identification and appropriate 
treatment of ligamentous shoulder pathology 
is considered one the more controversial areas 
in canine orthopedics.
• Outpatient—early diagnosis.
• Inpatient—chronic, severe disease requires 
• Bicipital tenosynovitis—50–75% success 
with medical treatment; requires surgery with 
evidence of chronic changes and failure of 
• Medial shoulder instability treatment 
depends on the severity of the disease with 
mild to moderate instability typically being 
amenable to conservative therapy, while severe 
ligamentous disruption and instability 
requiring medial shoulder stabilization.
• Subtotal rupture of the origin of the biceps 
brachii tendon generally requires surgery.
tendon—may be an incidental finding; 
requires surgery after excluding other causes 
of lameness and medical treatment.
• Avulsion or fracture of the supraspinatus 
tendon—often requires surgery because of 
persistent bone fragment irritation of the tendon.
muscle—requires surgery.NURSING CARE
post surgery; helps reduce inflammation and 
swelling at the surgery site; performed 5–10 
minutes every 8 hours for 3–5 days.
• Regional massage and range ­of­motion 
exercises—improve flexibility; decrease 
muscle atrophy.
• Rehabilitation therapy by a licensed 
veterinary rehabilitation professional is 
considered crucial to improve the speed of, 
and likelihood of recovery from shoulder 
pathology with or without surgical 
ACTIVITY
• Medical treatment—requires strict 
confinement for 4–6 weeks; activity; 
premature return to normal activity likely 
exacerbates signs and induces a chronic 
pathological state.
• Post surgery—depends on procedure 
DIET
Weight control—decrease the load applied to 
the painful joint.
• Bicipital tenosynovitis—recommended 
with poor response to medical treatment and 
chronic disease; goal: eliminate movement of 
the biceps tendon within the inflamed 
synovial sheath by performing a tenodesis or, 
more commonly, release of the bicipital 
tendon; either arthroscopic, or open, or 
percutaneous (± ultrasound guidance) 
tendon release.
origin—reattach tendon to the proximal 
lateral aspect of the humerus with a screw 
and spiked washer or pass the tendon 
through a bone tunnel and suture it to the 
supraspinatus tendon. Alternatively 
arthroscopy to confirm complete release of 
the tendon, followed by rehabilitation therapy 
• Medial shoulder instability—sporadic and 
conflicting reports of the efficacy of radio­
frequency capsulorrhaphy for moderate 
pathology. Prosthetic ligament reconstruction 
for the treatment of severe instability is 
tendon—longitudinally incise the tendon; 
remove the calcium deposits.
tendon—remove the bone fragment(s).
muscle—tenotomy and excision of part of the 
tendon of insertion; often feel a distinct pop 
after excision of the last adhesion, which 
allows complete range of motion of the 
shoulder joint.Shoulder Joint, Ligament, and Tendon Conditions  (continued)

Canine and Feline, Seventh Edition  1249
S  MEDICATIONS
• Local therapy—intra ­articular injection 
(corticosteroid or platelet rich plasma)—
initial treatment of choice.
• Do not inject into a septic joint; perform 
complete synovial fluid analysis if any 
doubt.
• Prednisolone acetate 20–40 mg, depending 
on size.
• Lameness markedly improved but not 
eliminated—give a second injection in 3–6 
weeks.
• Systemic treatment (nonsteroidal anti ­
inflammatory drugs [NSAIDs] or steroids)—
not as effective.
• Incomplete resolution—recommend 
surgery.
NSAIDs and Analgesics
kg PO q24h.
• Etodolac 10–15 mg/kg PO q24h.
>3.6 kg.
PO q24h.
• Avoid prolonged use of corticosteroids 
because of the potential side effects and 
long­term intra ­articular use.• Direct injection of a corticosteroid into the 
biceps tendon—may promote further tendon 
disruption and eventual rupture.
patients.
• Chondroprotective drugs, e.g., polysulfated 
glycosaminoglycans, green ­lipped mussel 
extract, and glucosamine/chondroitin sulfate 
(limited supportive data)—may help limit 
associated cartilage damage and degeneration.
• Nonspecific anti ­inflammatory supplements, 
e.g., green ­lipped mussel extract and omega 
3 fatty ­acid supplementation.
  FOLLOW-UP
Most patients require a minimum of 1–2 
months of rehabilitation after treatment.
• Medically managed bicipital 
tenosynovitis—often successful after one or 
two treatments (50–75% of cases) with no 
chronic changes.
• Surgically treated bicipital tenosynovitis—
good to excellent results (90% of cases); 
recovery to full function may take 2–8 months.
• Surgically treated release or tenodesis of the 
bicipital brachii tendon—good to excellent 
prognosis; >85% of patients show improved 
return to function.
• Surgically treated medial shoulder 
instability—variable results and highly 
dependent on concurrent pathology and 
adherence to postoperative restriction and 
rehabilitation therapy.• Surgically treated mineralization of the 
supraspinatus tendon—good to excellent 
prognosis; recurrence possible but uncommon.
• Surgically treated avulsion or fracture of the 
• Surgically treated fibrotic contracture of the 
infraspinatus muscle—good to excellent 
prognosis; patients uniformly return to 
normal limb function.
drug.
Laitinen OM, Flo GL. Mineralization of the 
supraspinatus tendon in dogs: a long ­term 
follow ­up. J Am Anim Hosp Assoc 2000, 
36(3):262–267.
Rivers B, Wallace L, Johnston GR. Biceps 
tenosynovitis in the dog: radiographic and 
sonographic findings. Vet Comp Orthop 
T raumatol 1992, 5:51–57.
Schaefer SL, Forrest LJ. Magnetic resonance 
imaging of the canine shoulder: an 
anatomic study. Vet Surg 2006, 35(8): 
721–728.
Acknowledgmen t The author/editor 
Walter C. Renberg. 
available online(continued)  Shoulder Joint, Ligament, and Tendon Conditions

S
1250  Blackwell’s Five-Minute Veterinary Consult  
S  BASICS
A disorder of impulse formation within, and 
conduction out of, the sinus node; dysfunction 
of subsidiary pacemakers and other segments 
of the cardiac conduction system frequently 
coexist with the sinus node dysfunction.
• Arrhythmias noted with sick sinus 
syndrome (SSS) include any or all of the 
following: inappropriate sinus bradycardia, 
sinus pauses (representing sinus arrest or 
sinoatrial exit block), slow ectopic atrial 
rhythm, or alternating periods of sinus 
bradyarrhythmias and supraventricular 
tachycardia (SVT) (Figure 1).  • Paroxysms of 
SVT may alternate with prolonged periods of 
sinus node inertia and often atrioventricular 
(AV) nodal inertia as well, producing 
tachycardia–bradycardia syndrome, a variant 
of SSS. • P waves and QRS complexes are usually normal. • P waves may be abnormal 
or absent with slow atrial ectopic rhythm or 
junctional escape rhythm.
• ECG manifestations may precede 
development of clinical signs. • Clinical signs 
usually result from the failure of subsidiary 
pacemakers to generate escape rhythms when 
sinus node dysfunction occurs. • The common 
clinical manifestations reflect transient 
decreases in organ perfusion, particularly 
reduced cerebral and skeletal muscle perfusion. 
• Rarely, congestive heart failure develops.
• Cardiovascular. • Nervous, musculoskeletal, 
and renal systems may be secondarily affected 
because of hypoperfusion.
GENETICS
• May be heritable in miniature schnauzers 
and West Highland white terriers. 
• Doberman pinschers and boxers can have 
syncope associated with long sinus pauses, 
suggestive of SSS.SIGNALMENT
Species
Dog
• Miniature schnauzer (may be heritable). 
• Noted commonly in cocker spaniel, 
dachshund, and West Highland white 
terrier.
Most dogs >6 years old.
Female
SIGNS
• Clinical signs vary from asymptomatic to 
weakness, syncope, collapse, and/or seizures. 
• Sudden death is infrequent.
• Heart rate may be abnormally rapid or 
abnormally slow. • Pauses may be noted. 
• Some patients appear normal.Sick Sinus Syndrome
Figure 1 .
A continuous lead II rhythm strip (25 mm/s) recorded from a dog with sick sinus syndrome showing an ectopic atrial rhythm interrupted by several short pauses. 
The third pause initiates a paroxysm of supraventricular tachycardia (250 bpm) followed by asystole (6.6 seconds) terminated by a junctional escape complex.

Canine and Feline, Seventh Edition  1251
SSCAUSES
• Idiopathic. • Familial in miniature schnauzers. 
• Metastatic disease. • Ischemic disease.
  DIAGNOSIS
• Healthy dogs may exhibit sinus bradycardia 
(rate as low as 30 beats/min) and sinus pauses 
(as long as 3.5 seconds) normally during sleep. 
• Bradycardia and sinus arrest due to normal 
or enhanced vagal tone. • Drug-induced 
(digitalis, α-adrenergic antagonists, α2-
adrenergic agonists, calcium channel 
antagonists, cimetidine, opioids).  • Seizures 
or syncope due to noncardiac disease. • Atrial 
standstill secondary to hyperkalemia or atrial 
disease. • Weakness due to neurologic, 
musculoskeletal, or metabolic diseases.
Normal
IMAGING
Breeds predisposed to SSS are also 
 predisposed to degenerative valvular disease; 
echocardiography may be used to confirm 
presence of significant valvular disease when 
heart murmur is present.
• Atropine response testing—indicated in dogs 
with sinus bradycardia, sinus arrest, and sinoatrial 
exit block. Administer atropine 0.04 mg/kg IM 
and evaluate the ECG 20–30 minutes later. A 
normal (positive) response is >50% increase in 
heart rate with abolishment of pauses; dogs with 
SSS generally have no response or an incomplete 
response to atropine. • Electrophysiologic testing 
of sinus node recovery time and sinoatrial 
conduction time. • 24-hour ambulatory ECG 
(Holter) or event recording to correlate clinical 
signs with arrhythmia.
  TREATMENT
• Hospitalization rarely necessary except for 
electrophysiologic testing or pacemaker 
implantation. • Do not treat asymptomatic 
animals.
ACTIVITY
Avoid vigorous exercise and stressful 
DIET
Modifications unnecessary.
Owner should be aware that medical 
management is often ineffective.SURGICAL CONSIDERATIONS
• Permanent artificial pacemaker necessary 
for dogs failing to respond to medical 
treatment and those exhibiting unacceptable 
medication side effects. • Permanent artificial 
pacemaker usually required for dogs with 
bradycardia–tachycardia syndrome. 
• T ransvenous placement of a pacing lead in 
the right atrium or auricle may successfully 
abolish the sinus pauses.
• Do not treat asymptomatic animals. 
• Symptomatic dogs are grouped into those 
showing primarily bradycardia, sinus arrest, 
and/or sinoatrial exit block and those with 
supraventricular tachycardia followed by sinus 
arrest.  • Atropine-responsive symptomatic dogs 
with bradycardia or sinus arrest—anticholiner -
gic agents (propantheline: small dogs, 3.75–7.5 
mg PO q8–12h; medium dogs, 15 mg PO q8h; 
large dogs, 30 mg PO q8h; hyoscyamine: 
3–6 μg/kg q8h). • Dogs with bradycardia and 
sinus arrest—may try theophylline (Theo-Dur) 
20 mg/kg PO q12h, terbutaline 0.2 mg/kg PO 
q8–12h, or hydralazine 1–2 mg/kg PO q8–12h 
if anticholinergic drugs are ineffective (avoid 
hydralazine if patient is hypotensive). • Dogs 
with bradycardia–tachycardia whose clinical 
signs are due to tachycardia or tachycardia-
induced sinus arrest—can give digoxin 5 μg/kg 
PO q12h or atenolol 0.5–1 mg/kg PO q12–24h 
in attempt to suppress the SVT (monitor closely 
for exacerbation of bradycardia). • Therapy for 
tachycardias should only be considered, once 
pacing is established to avoid worsening of 
bradyarrhythmias.
Avoid drugs that may worsen sinus node 
dysfunction (e.g., β-adrenergic antagonists, 
calcium channel blocking agents, phenothia-
zines, class I and III antiarrhythmic agents, 
opioids, cimetidine, α2-adrenergic agonists).
• Attempts to manage bradycardia–tachycardia 
syndrome medically without prior pacemaker 
implantation carry significant risk because 
drugs used to control SVT may worsen the 
bradyarrhythmias, and vice versa. • Adverse 
effects of anticholinergic medication (constipa -
tion, difficulty voiding, keratoconjunctivitis 
sicca, emesis, anxiety) occur commonly.
  FOLLOW-UP
• ECG in asymptomatic patients—to detect 
progression of disease. • ECG in patients treated medically or with pacemaker 
• Rarely, reduced cerebral or renal perfusion 
results in chronic renal dysfunction or CNS 
damage. • Presence of significant valvular 
disease has implications for type of perma-
nent pacing mode selected.
• Good, following pacemaker 
implantation in animals without congestive 
heart failure. • Medical management—often 
ineffective; initial beneficial effects often not 
sustained.
SYNONYMS
• Bradycardia–tachycardia syndrome. • Sinus 
node dysfunction. • Tachycardia–bradycardia 
syndrome.
SEE ALSO
• Sinus Arrest and Sinoatrial Block.
• Sinus Bradycardia.
• Supraventricular Tachycardia.
• ECG =  electrocardiogram.
• SSS = sick sinus syndrome.
Kraus MS, Gelzer ARM. T reatment of cardia 
arrhythmias and conduction disturbances. 
Sleeper M. Manual of Canine and Feline 
Saunders Elsevier, 2016, pp. 313–329.
Electrocardiography of the Dog and Cat. 
Willis, R., Oliveira, P ., Mavropoulou, A. 
Guide to Canine and Feline 
Electrocardiography. Ames, IA: Wiley-
Blackwell, 2018.
Smith, Jr.
available online(continued)  Sick Sinus Syndrome

S
1252  Blackwell’s Five-Minute Veterinary Consult  
S  BASICS
• Sinus arrest—a disorder of impulse 
formation caused by slowing or cessation of 
spontaneous sinus nodal automaticity; failure 
of the sinoatrial (SA) node to initiate an 
impulse at the expected time. P-P interval 
does not equal a multiple of basic P-P 
interval. • Sinoatrial block—a disorder of 
impulse conduction; an impulse formed 
within the sinus node fails to depolarize the 
atria or does so with delay; most commonly 
the basic rhythmicity of the sinus node is not 
disturbed and the duration of the pause is a 
multiple of the basic P-P interval. Classified 
into first-, second-, and third-degree SA block 
(similar to degrees of atrioventricular [AV] 
block). Difficult to diagnose first- and third- 
degree SA block from electrocardiogram 
(ECG). Second-degree SA block most common: 
Mobitz type I (Wenckebach) SA block— 
P-P interval progressively shortens prior to a 
pause; duration of pause is less than two P-P 
cycles; Mobitz type II SA block—duration of 
pause occurring after a sinus beat is exact 
multiple (two, three, or four times normal) of 
basic P-P interval.
• A normal P wave exists for each QRS 
complex with a pause equal to or greater than 
twice the normal P-P interval; rhythm is 
regularly irregular or irregular with pauses 
(Figure 1). • Junctional or ventricular escape 
beats—occur if pauses significantly prolonged. 
Subsidiary pacemaker takes over rhythm with 
escape beats normally from AV junctional 
tissue or Purkinje fibers; intermittent absence 
of P waves noted or P waves may be negative 
and precede, be superimposed on or follow 
the QRS complexes. • Surface ECG cannot 
differentiate sinus arrest from block in the 
dog because of normal R-R interval variation 
(sinus arrhythmia).PATHOPHYSIOLOGY
• Sympathetic and parasympathetic influences 
can alter spontaneous sinus node depolari -
zation; vagal stimulation of acetylcholine, 
which binds to SA nodal receptor sites, can 
slow automaticity of the sinus node by 
reducing the slope of phase 4 depolarization; 
sympathetic stimulation releases norepineph -
rine that binds to β1 receptors on the SA node, 
enhancing spontaneous SA nodal discharge 
rate. • An overdrive inhibition phenomenon 
occurs when sinus arrest follows a run of 
ectopic beats. The sinus node requires a 
warming-up period until the usual rate of 
automaticity is reestablished. • Intrinsic disease 
of the sinus node may affect the balance 
between the parasympathetic and sympathetic 
efferent traffic to the SA node and its 
spontaneous discharge rate. • Duration of 
sinus arrest may be long and possibly irrevers -
ible when the sinus node is suppressed by an 
ectopic tachycardia, particularly with severe 
underlying heart disease. Persistent sinus arrest 
that is not drug induced often indicates sick 
sinus syndrome (SSS).
Cardiovascular—clinical signs of weakness or 
syncope may appear if sinus arrest or block 
causes sufficiently long periods (generally 5 
seconds or longer) of ventricular asystole with 
no escape beats initiated by latent pacemakers.
GENETICS
• Seen in purebred pugs with hereditary 
stenosis of the bundle of His. • Seen in 
female miniature schnauzers predisposed to 
SSS. Is the most common arrhythmia in 
miniature schnauzers with SSS. 
• Congenitally deaf Dalmatian coach hounds 
often have abnormal SA node and multiple 
atrial arteries. May be a genetic component to 
the cause of SSS in those breeds predisposed 
(see Breed Predilections).
• Normal incidental finding in 
brachycephalic breeds of dogs in which inspiration causes a reflex increase in vagal 
tone. • Common in dog breeds predisposed 
to SSS. • Uncommon in cats.
N/A
Species
• Brachycephalic breeds. • Breeds predisposed 
to SSS (e.g., miniature schnauzers, dachshunds, 
cocker spaniels, pugs, boxers and West Highland 
white terriers).
If associated with SSS, generally middle-aged 
to older animals.
If associated with SSS, older females.
SIGNS
Generally no clinical significance by itself if 
terminated by sinus node depolarization, or 
latent pacemakers promptly escape to prevent 
ventricular asystole.
• Usually none. • Signs of low cardiac output 
(e.g., weakness and syncope) may occur with 
failure of the SA node to fire on time if no 
lower pacemaker focus takes over the rhythm. 
• Sudden death is possible should prolonged 
periods of ventricular asystole occur.
• May be normal. • Heart sounds following a 
pause may be louder because the ventricles 
have longer filling time and therefore eject a 
larger amount of blood. • Extremely slow 
heart rate if arrest or block is prolonged or 
frequent. • With significant pathologic 
cardiac disease—may be findings consistent 
with poor cardiac output (e.g., prolonged 
perfusion time, pale mucous membranes, 
weak femoral pulses).Sinus Arrest and Sinoatrial Block
Figure 1 .
Intermittent sinus arrest in a brachycephalic breed with an upper respiratory disorder. The pauses (1 and 1.44 seconds) are greater than twice the normal P-P 
interval (0.46). (Source: From Tilley LP . Essentials of Canine and Feline Electrocardiography, Interpretation and T reatment, 3rd ed. Baltimore, MD: Williams and 
Wilkins, 1992, Reprinted with permission of Wolters Kluwer.)

Canine and Feline, Seventh Edition  1253
SSCAUSES
• Vagal stimulation secondary to coughing, 
pharyngeal irritation. • Ocular or carotid 
sinus pressure. • Surgical manipulation.
• Degenerative heart disease (fibrosis). 
• Dilatory heart disease. • Acute myocarditis. 
• Neoplastic heart disease. • SSS. • Irritation 
of vagus nerve secondary to thoracic or 
cervical neoplasia. • Electrolyte imbalance. 
• Drug toxicity (e.g., digoxin).
• Certain drugs, including digitalis, quinidine, 
propranolol, xylazine, acepromazine, 
hydromorphone. • Respiratory tract disease. 
• Vagal maneuvers.
  DIAGNOSIS
• Marked sinus arrhythmia and sinus 
bradycardia. • Not always possible to 
differentiate sinus arrest from SA block 
without direct recordings of sinus node 
discharge; pauses that are precise multiples of 
the dominant beat interval suggest sinus block.
Serum electrolyte abnormalities, especially 
hyperkalemia (serum K+ >5.7 mEq/L).
N/A
IMAGING
• Thoracic radiographs if neoplastic or 
cardiac disease suspected. • Cardiac ultra -
sound if structural or neoplastic heart disease 
• Provocative atropine response test to assess 
sinus node function. Administer 0.04 mg/kg 
atropine IM; evaluate ECG lead II rhythm 
strip 30 minutes later for response or 
administer 0.04 mg/kg atropine IV followed 
by ECG in 10 minutes. Resolution of the 
arrhythmia suggests high vagal tone as the 
underlying cause. • Ambulatory monitoring 
may reveal prolonged periods of failure of 
impulses from the SA node if signs of 
weakness or syncope. • In humans, a period 
of sinus arrest following right carotid massage 
that lasts longer than 3 seconds suggests 
inappropriate sinus responsiveness. 
• Electrophysiologic studies of sinus node. 
• Serum digoxin concentration, if applicable; 
trough level recommended (just before next 
dose or at least 8 hours post pill); therapeutic 
serum concentrations are typically 
0.5–1.5 ng/mL.PATHOLOGIC FINDINGS
Histologic study of the SA node may reveal 
necrosis, fibrosis, and/or degenerative changes.
  TREATMENT
Asymptomatic sinus arrest or block does not 
require therapy. If clinical signs, therapeutic 
approach depends on cause, underlying 
cardiac status, and severity of symptoms. Any 
indicated treatment may be outpatient unless 
pacemaker implantation is necessary, which 
necessitates hospital management.
Correct any electrolyte abnormalities.
ACTIVITY
Unrestricted unless signs of weakness, 
syncope, or congestive heart failure (CHF) 
develop.
An artificial pacemaker may be necessary 
when patient is symptomatic and 
nonresponsive to medical management.
Implantation of an artificial demand 
pacemaker in animals with clinical signs 
nonresponsive to therapy.
• Only if patient is symptomatic, consider 
atropine 0.04 mg/kg IV, IM, glycopyrrolate 
5–10 μg/kg IV, IM, or isoproterenol 10 μg/kg 
IM, SC q6h or dilute 1 mg in 500 mL of 5% 
dextrose or Ringer’s solution, and infuse IV at 
0.04–0.08 μg/kg/min. • If responsive to 
injectable anticholinergic drugs (e.g., atropine)—
can prescribe parasympatholytic drug such as 
oral propantheline bromide 0.25–0.5 mg/kg 
q8–12h or hyoscyamine 3–6 μg/kg q8h for 
at-home management. Sympathomimetic 
agents including methylxanthine theophylline 
10 mg/kg extended release formulation q12h 
or terbutaline 0.2 mg/kg q8–12h PO (dogs) 
and 0.1–0.2 mg/kg q12h (cats) could be 
considered for oral therapy.
If patient is symptomatic secondary to 
prolonged pauses, discontinue any drugs that 
may be causative (e.g., digitalis, beta-blockers, 
calcium channel blockers).
Avoid drugs that depress SA node function.
If medical therapy does not resolve signs, 
consider pacemaker implantation.
  FOLLOW-UP
When indicated, periodic serial ECG 
evaluation to assess therapeutic efficacy and 
possible progression to a more serious 
dysrhythmia.
If associated with primary cardiac disease, 
CHF may develop and necessitate appropriate 
If cause is SSS, symptomatic patient may 
respond well to medical intervention; if 
poorly responsive, permanent pacemaker 
implantation would improve prognosis.
• Sick sinus syndrome. • Sinus arrhythmia. 
• Sinus bradycardia.
SYNONYMS
• Sinus block. • Sinus pause.
SEE ALSO
• Sick Sinus Syndrome.
• Sinus Arrhythmia.
Boyett MR, Honjo H, Kodama I. The 
sinoatrial node: a heterogeneous pacemaker 
structure. Cardiovasc Res 2000, 
47(4):658–687.
Issa ZF , Miller JM, Zipes DP . Sinus node 
dysfunction. In: Clinical Arrhythmology 
and Electrophysiology: A Companion to 
Braunwald’s Heart Disease. Philadelphia, 
PA: Saunders, 2008, pp. 118–126.
Joung B, Ogawa M, Lin S-F , Chen P-S. The 
calcium and voltage clocks in sinoatrial 
node automaticity. Korean Circ J 2009, 
39(6):217–222.
Kittleson MD, Kienle RD. Small Animal 
Cardiovascular Medicine. St. Louis, MO: 
Mosby, 2005.
Author  Deborah J. Hadlock
Consulting Editor  Michael Aherne(continued)  Sinus Arrest and Sinoatrial Block

1254  Blackwell’s Five-Minute Veterinary Consult  
S  BASICS
• Normal sinus impulse formation 
characterized by a phasic variation in sinus 
cycle length. An irregular R-R interval is 
present that has more than 10% variation in 
sinus cycle length (or variability of 0.12 
seconds [dog], 0.10 seconds [cat], or more 
exists between successive P waves) (Figure 1).
• T wo basic forms exist—respiratory sinus 
arrhythmia (RSA): P-P interval cyclically 
shortens during inspiration due primarily to 
reflex inhibition of vagal tone and lengthens 
during expiration; nonrespiratory sinus 
arrhythmia: phasic variation in P-P interval 
unrelated to the respiratory cycle.
• Other than the irregular rhythm, all other 
criteria for sinus rhythm are present.
• Normal heart rate.
• Positive P wave in leads, I, II, III, and aVF , 
unless a wandering pacemaker is present, 
where the P waves may be positive, diphasic, 
or negative temporarily.
• A P wave is present for every QRS complex.
• A QRS complex is present for every P wave.
• PR interval is relatively constant.
• Sinus node discharge rate depends on the 
two opposing influences of the autonomic 
nervous system. Vagal stimulation decreases 
spontaneous sinus nodal discharge rate and 
predominates over sympathetic stimulation. 
Negative intrathoracic pressure occurring with 
inspiration causes decreased pressure on the 
vagus nerves. Feedback from the cardioregula -
tory and vasomotor centers in the medulla 
produces cardiac acceleration by decreasing 
vagal restraint on the sinus node; the opposite 
occurs during exhalation. The genesis of sinus 
arrhythmia also depends on reflexes involving 
pulmonary stretch receptors (Hering–Breuer reflex), pressure–volume sensory receptors in 
the heart (Bainbridge reflex whereby atrial 
stretch stimulates receptors in the atrial wall, 
causing vagal inhibition and increase in heart 
rate; baroreceptors in the carotid sinus and 
aortic arch elicit inverse changes in heart rate 
with acute changes in arterial blood pressure), 
blood vessels, and chemical factors of the 
blood.
• RSA is measured as a high-frequency 
component of heart rate variability (HRV) 
and is used as an index of cardiac vagal 
control. HRV measures beat to beat changes 
in heart rate and R-R variability from the 
ECG. HRV is a widely accepted clinical and 
research tool for evaluation of cardiac 
autonomic changes.
Cardiovascular—generally no hemodynamic 
consequence, but marked sinus arrhythmia 
may produce a long enough sinus pause to 
produce syncope if not accompanied by an 
escape rhythm.
GENETICS
N/A
Most frequent form of arrhythmia in dogs.
Species
• RSA frequent normal finding in dogs.
• While common in cats asleep and in home 
environment, in a clinical setting sympathetic 
dominance occurs and RSA is rare without 
• Brachycephalic breeds predisposed.
• Dogs—bulldog, Lhasa apso, Pekingese, 
pug, shar-pei, shih tzu, boxer.
• Cats—Persian, Himalayan.
N/A
N/ASIGNS
• Uncommon, but weakness may develop 
if pauses between beats are excessively 
long; syncope can occur when a marked 
sinus arrhythmia and sinus bradycardia 
develop.
• In general, symptoms more common in 
nonrespiratory than in respiratory form.
• RSA—none.
• Nonrespiratory sinus arrhythmia—may be 
findings related to underlying disease.
• Irregular rhythm on auscultation.
• May be findings related to specific disease 
accentuating vagal tone (e.g., stertor and 
stridor in a patient with brachycephalic 
airway syndrome).
CAUSES
• Normal cyclic change in vagal tone 
associated with respiration in the dog; heart 
rate increases with inspiration and decreases 
with expiration.
• Underlying conditions that increase vagal 
tone—high intracranial pressure, 
cerebral disorders, digitalis toxicity, organo- 
phosphates.
• Carotid sinus massage or ocular pressure 
(vagal maneuver) may accentuate.
• Brachycephalic conformation.
• Digoxin therapy.
• Any disease that increases vagal tone.
  DIAGNOSIS
• Auscultation of sinus arrhythmia is often 
confusing; ECG helps differentiate normal Sinus Arrhythmia
Figure 1 .
Respiratory sinus arrhythmia with an average rate of 120 bpm (6 complexes between 1 set of time lines or 3 seconds × 20) (paper speed, 25 mm/s; 10 mm/mV). 
The rate increases during inspiration (INSP) and decreases during expiration (EXP). The fluctuation of the baseline correlates with the movement of the electrodes 
by the thoracic cavity. (Source: From Tilley LP . Essentials of Canine and Feline Electrocardiography, 3rd ed. Baltimore: Williams & Wilkins, 1992. Reprinted with 

Canine and Feline, Seventh Edition  1255
Ssinus arrhythmia from true pathologic 
• Wandering sinus pacemaker frequently 
associated and a variant of sinus arrhythmia. 
Site of impulse formation shifts within the 
sinoatrial node or to an atrial focus or 
atrioventricular (AV) node, changing the 
configuration of the P wave.
• Important to differentiate normal sinus 
arrhythmia from pathologic arrhythmias 
including atrial premature complexes, sick 
sinus syndrome, slow atrial fibrillation, and 
AV dissociation.
N/A
Cats with chronic respiratory disease may be 
positive for feline leukemia virus or feline 
IMAGING
Radiographs, CT, or MRI of head and 
neck to assess for abnormal anatomic 
conformation that might predispose to airway 
problems.
• Pharyngoscopy/laryngoscopy if upper 
airway disease suspected.
• Atropine challenge test (administer atropine 
0.04 mg/kg IM followed by ECG in 30 
minutes or 0.04 mg/kg atropine IV followed 
by ECG in 10 minutes) if associated with 
sinus bradycardia and primary dysfunction of 
sinus node is suspected. Subsequent heart rate 
should be greater than 150 bpm.
See specific disease.
  TREATMENT
Generally, specific treatment required only 
when associated with symptomatic sinus 
bradycardia; if not related to respiration, 
underlying cause is treated. If patient is 
suffering respiratory distress, appropriate 
inpatient management indicated until patient 
is stable.
None unless associated with underlying 
disease.
ACTIVITY
Not restricted unless associated with specific 
disease (e.g., brachycephalic animals may 
need to limit exercise, especially in high 
ambient temperatures).DIET
Caloric restriction for obese animals with 
airway compromise.
None unless associated with specific disease.
• Generally no therapy indicated; this is a 
normal rhythm.
• Infectious respiratory diseases require 
appropriate antibiotic therapy.
• If associated with symptomatic sinus 
bradycardia or sinus arrest or block, 
 anticholinergics may be indicated—atropine 
0.02–0.04 mg/kg IV, IM, SC or glycopyrrolate 
5–10 μg/kg IV, IM, SC.
Discontinue digoxin if toxicity is a problem.
Avoid atropine in patients with respiratory 
disease; an adverse effect is drying of 
N/A
N/A
  FOLLOW-UP
Only if associated with specific disease.
N/A
N/A
N/A
• Asthma.
• Chronic obstructive pulmonary disease.AGE-RELATED FACTORS
Generally more pronounced in young adult.
N/A
Increased incidence of arrhythmias.
SYNONYMS
• Nonrespiratory sinus arrhythmia = 
nonphasic sinus arrhythmia; sinus 
irregularity.
• Respiratory sinus arrhythmia = phasic sinus 
• Ventriculophasic sinus arrhythmia—form 
of nonphasic sinus arrhythmia in which atrial 
cycles containing ventricular complexes are 
shorter than those in which they are absent. 
That is, the P-P interval that includes the 
QRS complex is shorter than the P-P interval 
without a QRS complex. This can be seen 
with second-degree AV block, complete AV 
block or in the presence of ventricular 
premature complexes with a full compensa-
tory pause.
SEE ALSO
• HRV = heart rate variability.
• RSA = respiratory sinus arrhythmia.
Billman GE. Heart rate variability—a 
historical perspective. Front Physiol 2011, 
2:86.
Bonow R, Mann D, Zipes D, Libby P . 
Braunwald’s Heart Disease: A Textbook of 
Cardiovascular Medicine, 9th ed. Ames, IA: 
Elsevier, 2012.
Côté E, MacDonald K, Meurs KM, Sleeper 
MM. Feline Cardiology. Ames, IA: 
Wiley-Blackwell, 2011.
Lewis K, Scansen BA, Aarnes TK. Respiratory 
sinus arrhythmia in an anesthetized cat. 
ECG of the month. J Am Vet Med Assoc 
2013, 242:623–625.
Yasuma F , Hayano J. Respiratory sinus 
arrhythmia: why does the heartbeat 
synchronize with respiratory rhythm? Chest 
2004, 125:683.
Consulting Editor  Michael Aherne(continued)  Sinus Arrhythmia

1256  Blackwell’s Five-Minute Veterinary Consult  
S  BASICS
Sinus rhythm in which impulses arise from 
the sinoatrial (SA) node at slower than 
normal rate for an animal’s signalment and 
activity (Figure 1).
• Dogs—sinus rate <60 bpm). • Cats—sinus 
rate <110 bpm at home or <130 bpm at the 
clinic. • Rhythm regular, often with a slight 
variation in R-R interval; may be irregular; 
often coexists with sinus arrhythmia. 
• Normal P wave for each QRS complex. 
• P-R interval constant.
• Can be an incidental finding in healthy 
animals or during sleep. • May represent 
normal physiologic response to athletic 
training; may result from enhanced cardiac 
parasympathetic tone or decreased sympa -
thetic tone as well as from intrinsic changes 
in the sinus node. • Automaticity of the 
heterogeneous sinus node is a very complex 
phenomenon invoking the calcium and 
voltage clock mechanisms. More than 16 
autonomically influenced currents with the If 
(funny) channel predominating and Ca2+ 
release from the sarcoplasmic reticulum 
critical to maintain autonomic balance and 
changes in heart rate. • May represent 
pathophysiologic response due to high vagal 
tone, change in blood pH, Pco2, Po2, or 
serum electrolyte disorders, hypothyroidism, 
increased intracranial pressure, toxins and 
certain drugs. • May be a result of sick sinus 
syndrome (SSS).
Cardiovascular—most instances benign 
arrhythmia; may be beneficial by producing a 
longer period of diastole and increased 
ventricular filling time; can be associated 
with syncope if due to abnormal reflex 
(neurocardiogenic) or intrinsic disease of 
sinus node.
GENETICS
Female miniature schnauzer, West Highland 
white terrier, boxer, cocker spaniel, 
dachshund, and pug predisposed to SSS—
may cause bradycardia.
• Common in the dog; less common in cat. 
• Clinical interpretation of sinus node rate 
also depends on environment and type of 
patient. For example, a sinus rate can be as 
low as 20 bpm in a normal dog that is 
sleeping.
Species
Bradycardia associated with SSS—miniature 
schnauzer, cocker spaniel, dachshund, pug, 
and West Highland white terrier.
• Decreased prevalence with advancing age 
unless associated with intrinsic disease of SA 
node. • SSS typically seen in middle-aged to 
With SSS, older female miniature schnauzers.
SIGNS
• Often asymptomatic. • Lethargy.
• Weakness. • Exercise intolerance. 
• Syncope. • Episodic ataxia.
• Pulse rate slow. • Hypothermia may be 
present. • Poor perfusion. • Syncope.
• Decreased level of consciousness.
CAUSES
• Athletic conditioning. • Hypothermia. 
• Intubation with pharyngeal or soft palate 
tension. • Sleep. • Cushing’s reflex with 
increased intracranial pressure. • Gastrointestinal 
distension. • Activation of baroreceptor reflex 
with increase in systemic blood pressure (BP).
Pathophysiologic
• High vagal tone associated with gastrointes-
tinal, respiratory, neurologic, and pharyngeal 
diseases. • Reflex-mediated/neurocardiogenic/
vasovagal—e.g., carotid sinus hyperactivity; 
situational (micturition, defecation, cough, 
swallowing).
• High intracranial pressure. • Hyperkalemia. 
• Hyper- or hypocalcemia. • Hypermagne -
semia. • Hypoxemia. • Hypothyroidism. 
• Hypoglycemia. • May precede cardiac 
arrest. • SSS (rare in the cat). • Feline dilated 
cardiomyopathy. • Viral myocarditis. • SA 
block. • In humans, mutations in the If 
channel and drugs which block If (such as 
ivabradine) have been associated with 
Pharmacologic
• General anesthesia. • Any negative chrono -
trope including: ◦ Phenothiazines. ◦ Beta-
adrenergic blockers. ◦ Digitalis glycosides. 
◦ Calcium channel blockers. ◦ α2-Adrenergic 
agonists. ◦ Sotolol. ◦ Amiodarone. ◦ Centrally 
acting opioids: morphine, hydromorphone, 
butorphanol, fentanyl.
• Any situation or disease that may increase 
parasympathetic tone. • Oversedation. 
• Hypoventilation under anesthesia. • Breeds 
predisposed to SSS.  DIAGNOSIS
• Persistent and marked sinus bradycardia 
(SB) should raise possibility of SSS. 
• Clinical signs may mimic cerebral 
• Hyperkalemia, hypercalcemia, hypocalcemia, 
or hypermagnesemia possible. • CBC and 
serum chemistry profile may reveal changes 
associated with metabolic disease such as 
• Serum thyroxine (T4), free T4, and thyroid-
stimulating hormone assays if hypothyroidism 
suspected. • Measure trough serum digoxin 
concentration, if applicable, 8 hours after last 
dose or close to next dosing; normal 
therapeutic serum concentration should be 
0.5–1.5 ng/mL. • Toxicologic screen.
sinus node function—administer atropine 
0.04 mg/kg IV, wait 10–15 minutes, then 
record ECG or administer same dose IM, 
wait 30 minutes, then record ECG; persistent 
sinus tachycardia at >140 bpm is expected 
response. Lower doses of atropine have 
increased tendency to cause initial accentua-
tion of SB and first- or second-degree 
atrioventricular block because of centrally 
mediated increase in vagal tone. • 24-hour 
Holter monitoring or ECG event recorder, an 
owner-triggered device, useful if transient 
bradyarrhythmia is suspected cause for 
  TREATMENT
• Many animals exhibit no clinical signs 
and require no treatment. In dogs without 
structural heart disease, heart rates as low as 
40–50 bpm generally provide normal 
cardiac output at rest. • Therapeutic 
approaches—vary markedly; depend on the 
mechanism for SB, the ventricular rate, and 
severity of clinical signs. • Inpatient or 
outpatient management—depends on 
underlying cause and clinical status of 
patient.
• Provide general supportive therapy including 
IV fluid therapy for hypothermic and 
hypovolemic patients. • Discontinue any 
causative drug. • Correct any serious electrolyte 
imbalance with appropriate fluid therapy.Sinus Bradycardia

Canine and Feline, Seventh Edition  1257
S
Figure 1 .
Sinus bradycardia at a rate of 75 bpm in a cat from anesthetic complications during surgery. Note the tall R waves. (Source: From Tilley LP . Essentials of Canine 
and Feline Electrocardiography, 3rd ed. Baltimore: Williams & Wilkins, 1992. Reprinted with permission of Wolters Kluwer.)
• Discuss importance of complying with 
daily medical management when treating. 
• Advise that persistent symptomatic 
bradycardia may necessitate permanent 
pacemaker implantation for reliable long-
term management.
• If progressive bradycardia occurs during 
anesthesia and is attributed to hypoventilation, 
immediately discontinue inhalation anesthetics 
and provide adequate ventilation; atropine is 
generally ineffective in this situation. • If surgical 
manipulation triggering vagal reflexes (eye, vagus 
nerve, larynx) is anticipated, pretreatment with 
atropine 0.02 mg/kg IM, SC or glycopyrrolate 
5–10 μg/kg IM, SC may prevent bradycardia. 
• Severe bradycardia may precipitate cardio  - 
pulmonary arrest; identify the causative agent or 
condition for effective management.
• If patient is hypothyroid, supplement with 
l-thyroxine. • For severe hypocalcemia 
(<6  mg/dL) administer 10% calcium gluconate 
0.5–1.5 mL/kg IV slowly over 15–30 minutes; 
monitor with ECG. • For symptomatic drug-  
induced bradycardias, disorders causing 
excessive vagal tone, and initial management of 
bradycardia associated with SSS, administer 
atropine 0.04 mg/kg IV or glycopyrrolate 
5–10  μg/kg IV; anticholinergic therapy may be 
continued short term using atropine 
0.02–0.04 mg/kg IM, SC q6–8h or glyco -
pyrrolate 0.01 mg/kg IM, SC q6–8h. Consider 
propantheline bromide 0.25–0.5 mg/kg PO 
q8–12h, hyoscyamine 3–6 μg/kg PO q8h, 
methylxanthine theophylline, an adenosine 
receptor antagonist (extended release formulation 
10 mg/kg PO q12h, dogs; 12.5 mg PO q24h in 
the evening, cats), and/or terbutaline (0.2 mg/
kg q8–12h PO, dogs; 0.625–1.25 mg/cat PO, 
cats) to manage symptomatic bradycardia 
associated with SA node disease.• For temporary management of symptomatic 
persistent bradycardia until pacing can be 
accomplished, consider continuous IV 
infusion of isoproterenol 0.04–0.08 μg/kg/
min IV. Temporary pacing, if available, would 
be the initial procedure of choice.
• For hypothermia-induced bradycardia with 
a pulse, rewarming and supportive measures 
should be mainstay of treatment. Parasym -
patho  lytics generally not recommended. 
• Parasympatholytic agents contraindicated 
for acidotic, hypercarbic patients under 
anesthesia (hypoventilation); bradycardia in 
this setting may protect the myocardium by 
decreasing oxygen consumption.
• Close ECG monitoring recommended 
when administering calcium solutions for 
treatment of hypocalcemia; if QT interval 
shortening or bradycardia, stop administra-
tion temporarily. • In patients with heart 
disease, a lower initial dose of l-thyroxine is 
advised to allow adaptation to higher 
metabolic rate. • Administer atropine 
selectively; rapid IV administration may 
predispose to ventricular arrhythmias by 
altering autonomic balance. • Caution when 
administering parasympatholytic agent to 
dogs with suspect SSS—could result in 
tachycardias that overdrive suppress escape 
rhythms and thus have a potential risk of 
asystole after termination of the tachycardia.
• Bradycardia associated with structural heart 
disease is most reliably treated by permanent 
pacemaker implantation. • Glycopyrrolate may 
have longer vagal blocking effect and cause less 
frequent ventricular ectopic beats than atropine.
  FOLLOW-UP
• Assess total T4 6 hours post pill. • Addison’s 
disease—assess electrolytes every 3–4 months after patient is stable. • ECG check of 
pacemaker function and pacing rate is 
recommended during each follow-up 
• Maintain normal Pao2 under anesthesia 
with proper ventilation; monitor with pulse 
oximetry or blood gases. • Avoid hypothermia 
intraoperatively.
• Signs, if present, should resolve with 
correction of causative metabolic or endocrine 
problem. • T reatment of symptomatic SB 
with a permanent pacemaker generally offers 
a good prognosis for rhythm control.
• Sick sinus syndrome. • Heart block. 
• Sinus arrhythmia.
Postparturient hypocalcemia usually develops 
1–4 weeks postpartum, but can occur at term, 
prepartum, or late lactation.
SEE ALSO
• Digoxin Toxicity. • Eclampsia. 
• Hypercalcemia. • Hyperkalemia. 
• Hypermagnesemia. • Hypocalcemia. 
• Hypothermia. • Hypothyroidism. 
• Organophosphate and Carbamate 
Toxicosis. • Sick Sinus Syndrome.
• ECG = electrocardiogram. • SA = 
sinoatrial. • SB = sinus bradycardia. • SSS = 
sick sinus syndrome. • T4 = thyroxine.
Kornreich B, Moïse NS. Bradyarrhythmias. 
In: Bonagura JD, T wedt D, eds. Current 
Veterinary Therapy XV. Ames, IA: Elsevier 
Saunders, 2014, pp. 731–737.
Consulting Editor  Michael Aherne(continued)  Sinus Bradycardia

S1258  Blackwell’s Five-Minute Veterinary Consult  
S  BASICS
Disturbance of sinus impulse formation; 
acceleration of the sinoatrial node beyond its 
normal discharge rate (Figure 1).
• Dogs—heart rate (HR) >160 bpm (puppies 
HR >220 bpm). • Cats—HR >180 bpm; 
(kittens HR >240 bpm). • ECG shows a rapid 
regular rhythm with possible slight variation in 
R-R interval. • P wave of sinus origin for each 
QRS complex with constant P-R interval. • P 
waves may be partially or completely fused 
with preceding T waves. • Generally has a 
gradual onset and termination.
• Accelerated phase 4 diastolic depolarization 
of sinus nodal cells (as a result of voltage- and 
calcium-dependent mechanisms) generally 
responsible for sinus tachycardia (ST). 
• Enhanced adrenergic effect or cholinergic 
inhibition results in high rate of sinus impulse 
formation; changes in heart rate usually 
involve a reciprocal action of the parasympa-
thetic and sympathetic divisions of the 
Cardiovascular—cardiac output = heart rate × 
stroke volume. Changes in heart rate affect 
preload, afterload, and contractility, which 
determine stroke volume; severe tachycardia 
can compromise cardiac output. Rapid rates 
shorten diastolic filling time, and particularly 
in diseased hearts, the increased heart rate can 
fail to compensate for decreased stroke volume, 
resulting in decreased cardiac output and 
coronary blood flow. Chronic tachycardias can 
cause cardiac dilation (tachycardiomyopathy) 
which often resolves with control of the 
tachycardia. However, ST is most often present 
due to elevated sympathetic tone and is 
physiologic (because of hypovolemia, fear, 
pain, etc.).
GENETICS
• Most common benign arrhythmia in the 
dog and cat. • Most common rhythm 
disturbance in the postoperative patient.
None
Species
None
SIGNS
Often no clinical signs because ST is almost 
always a consequence of a variety of physi-
ologic or pathophysiologic stresses.
• In general, ST itself does not produce any 
symptoms. • If associated with primary 
cardiac disease, weakness, exercise intolerance, 
or syncope may be reported. • If associated 
with other medical conditions, signs may be 
seen specific to the disease present.
• High HR. • May otherwise be normal if 
not associated with a pathologic condition. 
• Pale mucous membranes if associated with 
anemia or congestive heart failure (CHF). 
• Fever may be present. • Signs of CHF (e.g., 
dyspnea, cough, cyanosis, ascites) if associated 
with primary cardiac disease.
CAUSES
• Exercise. • Pain. • Restraint. • Excitement. 
• Any hyperadrenergic state.
• Fever. • CHF . • Chronic lung disease. 
• Shock. • Pericardial effusion. • Anemia. 
• Pain. • Infection. • Hypoxia. • Pulmonary 
thromboembolism. • Hypotension. 
• Hypovolemia. • Functional pheochromo -
cytoma. • Hyperthyroidism. • Pericarditis. 
• Pneumothorax. • Hypoglycemia. 
• Vestibulosympathetic hypovolemia.Pharmacologic
• Atropine. • Epinephrine. • Ketamine. 
• Tiletamine (Telazol®). • Quinidine. 
• Xanthine bronchodilators. • β-Adrenergic 
agonists.
• Thyroid medications. • Primary cardiac 
diseases. • Inflammation. • Pregnancy. 
• Anesthesia. • Certain toxins ( Amanita 
muscaria , scorpion venom, black widow 
spider venom), plants (Jimson weed, 
mandrake), and drugs (antihistamines, 
tricyclic antidepressants).
  DIAGNOSIS
Must differentiate from supraventricular 
tachycardia (SVT), including atrial 
tachycardia, atrial flutter with 2:1 AV block, 
and AV junctional tachycardia; as sinus rate 
increases, the P wave appears closer to the 
T wave of the previous beat. At very 
rapid rates, it becomes difficult to 
distinguish this condition from other 
pathologic SVT. Gradual slowing of the 
rate is suggestive of ST.
• Low packed cell volume if patient is 
anemic. • Leukocytosis with left shift if 
inflammation or infection is causative.
• High serum thyroxine (T4) or free T4 
concentration (cats) if secondary to 
hyperthyroidism. • T riiodothyronine (T3) 
suppression test and thyrotropin-releasing 
hormone (TRH) response test if T4 values 
are normal and hyperthyroidism is 
suspected. • Functional testing for 
pheochromocytoma: ◦ Metanephrines 
(breakdown metabolites of epinephrine and 
norepinephrine); measured in plasma or 
urine. ◦ Serum inhibin, a hormone involved 
in reproductive physiology; undetectable 
levels supportive of pheochromocytoma. 
• 24-hour Holter monitoring. • Cardiac Sinus Tachycardia
Figure 1 .
Sinus tachycardia at a rate of 272 bpm in a dog in shock. The rhythm is sinus because the P waves are normal, the P-R relationship is normal, and 
the rhythm is regular. (Source: From Tilley LP . Essentials of Canine and Feline Electrocardiography, 3rd ed. Baltimore: Williams & Wilkins, 1992. 
Reprinted with permission of Wolters Kluwer.)

Canine and Feline, Seventh Edition  1259
SSelectrophysiologic studies. • Plasma 
N-terminal pro-brain natriuretic peptide 
(NT-proBNP) assay may be helpful if 
evaluating for cardiac disease.
IMAGING
• Thoracic radiographs and echocardiography to 
evaluate for evidence of primary cardiac disease. 
• Thyroid scintigraphy to evaluate for hyperthy -
roidism. • Abdominal ultrasound and angiogra -
phy to evaluate for adrenal mass. • CT and MRI 
as well as functional imaging modalities very 
sensitive for detecting adrenal masses.
• A nonpharmacologic vagal maneuver can 
differentiate ST from other SVTs; carotid 
sinus or ocular pressure may terminate 
ectopic SVT. With effective vagal 
maneuvers, the HR in ST gradually slows. 
Less commonly, varying degrees of AV 
block (usually first-degree or Wenckebach) 
may occur transiently. ECG monitoring is 
recommended during these vagal 
maneuvers. • Pharmacologic agents can be 
used if no response to the vagal maneuver. 
Similarly, an abrupt reduction in HR 
suggests SVT whereas gradual slowing 
suggests ST: ◦ IV diltiazem 0.25 mg/kg 
administered over 2 minutes. If no 
response, can be repeated in 15 minutes. 
◦ IV esmolol 50–100 μg/kg bolus q5min 
up to 500 μg/kg; 25–200 μg/kg/min CRI. 
• A precordial thump may be used to 
differentiate ST from other SVT. ST 
usually not affected, whereas the SVT may 
stop for at least 1 or 2 beats. • Serial 
arterial BP measurement may document 
hypertension in patients with hyperthyroidism, 
pheochromocytoma, or renal disease.
• None if associated with physiologic or 
pharmacologic cause. • Pathologic findings 
depend on the primary disease process.
  TREATMENT
• Identify and correct underlying disorders 
whenever possible. • Whether inpatient or 
outpatient depends on clinical status of 
patient and primary disease, if any (e.g., if 
CHF , treat as outpatient unless animal is 
dyspneic or severely hypotensive). • If 
associated with pericardial effusion, avoid 
drug therapy and perform pericardiocentesis. 
• If associated with a certain drug (e.g., 
hydralazine, bronchodilators), discontinue the 
medication or adjust the dose. • If associated 
with hypovolemia, replace fluid volume.
Depends on whether associated with a 
specific disease.ACTIVITY
Exercise restriction recommended if 
symptomatic cardiac disease.
DIET
Sodium restriction generally advised with 
hypertension and CHF .
Discuss importance of managing any primary 
disease appropriately, with medical or surgical 
• Thyroidectomy—treatment option for 
hyperthyroidism (cats). • T umor removal is 
the definitive treatment for patients with 
• Establish underlying cause and treat 
appropriately; specific antiarrhythmic therapy is 
generally limited to patients in CHF or those 
with secondary cardiac disease due to hyperthy -
roidism or hypertension. • Dogs—if CHF is 
the cause, administer pimobendan along with 
appropriate diuretic therapy and angiotensin-
converting enzyme inhibitor. Digoxin may be 
indicated in some cases such as CHF with atrial 
fibrillation. If ST persists despite above 
management, consider adding a calcium 
channel blocker (e.g., diltiazem 0.5–2.5 mg/kg 
PO q8h) or a beta-blocker (e.g., atenolol 0.25–1 
mg/kg q12h, sotalol 1–2 mg/kg q12h PO) only 
after congestion is controlled. • Cats—if ST is 
associated with hyperthyroidism without CHF , 
a beta-blocker (e.g., atenolol 0.25–1 mg/kg PO 
q12–24h) may lower the HR. Consider digoxin 
(0.01875–0.03125 mg per average-size cat, 
equal to 1/8–1/4 of a 0.125 mg tablet—tablet 
preferred) if CHF present with atrial fibrillation 
and rapid ventricular response rate. Although 
still controversial, pimobendan (0.1–0.3 mg/kg 
PO q12h) has become more commonly 
accepted as treatment for CHF . If ST associated 
with hypertrophic cardiomyopathy, administer 
atenolol 6.25–12.5 mg/cat PO q12h or 
diltiazem 1.75–2.4 mg/kg PO q8h.
Avoid drugs such as atropine or catecholamines 
(epinephrine) that may further increase the HR.
• Beta-blockers can potentially worsen signs of 
congestion and lower cardiac output in patients 
with systolic dysfunction. • Suppression of ST 
may be catastrophic if occurring as natural 
compensatory response to maintain cardiac 
output in a systemically ill patient.
See manufacturer’s insert for specific drugs.
Depends on specific disease—for CHF , serial 
ECG, thoracic radiographs, BUN, creatinine, 
and serum electrolytes; for hyperthyroidism, 
serial serum T4, complete blood count, and 
biochemistry.
Minimize stress, exercise, and dietary sodium, 
if heart disease.
• Weakness or syncope if associated with 
low cardiac output. • Development of CHF if 
persistent ST associated with heart disease.
• ST usually resolves with correction of the 
underlying cause. • Poor despite treatment if ST 
is associated with CHF . • Favorable for remission 
of ST when hyperthyroidism is controlled 
medically, surgically, or by radioactive iodine.
See list of pathologic and physiologic causes.
Increase in cardiac output in late pregnancy (third 
trimester) largely due to an accelerated HR.
SYNONYMS
• Inappropriate sinus tachycardia. • Postural 
tachycardia syndrome.
SEE ALSO
• Atrial Fibrillation and Atrial Flutter. 
• Congestive Heart Failure—Left-Sided. 
• Congestive Heart Failure—Right-Sided. 
• Hyperthyroidism. • Pheochromocytoma. 
heart failure. • ECG = electrocardiogram. • HR 
= heart rate. • NT-proBNP = N-terminal 
pro-brain natriuretic peptide. • ST = sinus 
tachycardia. • SVT = supraventricular tachycar -
dia. • T3 = triiodothyronine. • T4 = thyroxine. 
Côté E, MacDonald K, Meurs K, Sleeper M. 
Feline Cardiology. Chichester, UK: Wiley- 
Blackwell, 2011.
Olshansky, B., Sullivan, R. Inappropriate 
sinus tachycardia. J Am Coll Cardiol 2013, 
61(8):793–801.
Consulting Editor  Michael Aherne(continued)  Sinus Tachycardia

1260  Blackwell’s Five-Minute Veterinary Consult  
SSjögren-Like Syndrome
  BASICS
OVERVIEW
• A systemic autoimmune disease 
characterized by keratoconjunctivitis sicca, 
xerostomia, and lymphoplasmacytic adenitis.
• Underlying mechanism unknown; however, 
autoantibodies directed against glandular 
tissues have been identified.
• Associated with other autoimmune or 
immune-mediated diseases, such as 
rheumatoid arthritis and pemphigus.
• Higher incidence in several canine 
breeds—English bulldogs, West Highland 
white terriers, and miniature schnauzers.
• Chronic disease of adult dogs.
• Cats unaffected.
SIGNS
• Adult onset.
• Conjunctivitis and keratitis.
• Keratitis sicca most prominent clinical 
feature.
• Corneal lesions (opacity to ulceration).
• Possible genetic predisposition in breeds 
with high incidence.
• Develops concurrently with other immune-
mediated and autoimmune diseases.
  DIAGNOSIS
• Other causes of keratoconjunctivitis 
sicca—canine distemper, trauma, and drug 
• Keratoconjunctivitis sicca associated with 
other immune-mediated diseases—atopy, 
lymphocytic thyroiditis, polymyositis, 
systemic lupus erythematosus, rheumatoid 
arthritis, and pemphigoid diseases.
Normal
• Hypergammaglobulinemia revealed by 
serum protein electrophoresis.
• Positive antinuclear antibody test.
• Positive lupus erythematosus cell test.• Positive rheumatoid factor test.
• Positive indirect fluorescent antibody test 
for autoantibodies.
IMAGING
N/A
Schirmer tear test (0–5 mm/min; reference 
interval is 15–20 mm/min).
• Histologic changes in salivary glands—
lymphoplasmacytic adenitis.
• Conjunctival biopsy—conjunctivitis.
  TREATMENT
• Directed at controlling keratoconjunctivitis 
sicca.
• Any concurrent disease must be medically 
managed.
• May include administration of anti-
inflammatory or immunosuppressive drugs.
• Surgical management of 
keratoconjunctivitis sicca indicated in animals 
that fail to respond to medical treatment.
• Topical tear preparations.
• Appropriate topical antibiotics for 
secondary bacterial infection, if present.
• Immunosuppressive or anti-inflammatory 
drugs.
• For more aggressive medical treatment and 
surgical intervention, see Keratoconjunctivitis 
Sicca.
Use of topical steroids in patients with acute 
keratoconjunctivitis sicca may cause corneal 
ulceration and is not recommended.
  FOLLOW-UP
• Reexamine patients weekly until 
keratoconjunctivitis sicca controlled.
• Additional monitoring may be indicated to 
manage underlying or concurrent disease.
• Immunosuppressive drugs—monitor 
patients every other week for possible side 
effects.
• Prognosis variable and depends on existence 
of concurrent disease.  MISCELLANEOUS
SEE ALSO
Keratoconjunctivitis Sicca.
Quimby FW, Schwartz RS, Poskitt T, et al. 
A disorder of dogs resembling Sjogren’s 
syndrome. Clin Immunol Immunopathol 
1979, 12:471–476.

Canine and Feline, Seventh Edition  1261
SSkin Fragility Syndrome, Feline
  BASICS
OVERVIEW
• A disorder of multifactorial causes 
characterized by extremely fragile skin.
• Tends to occur in old cats that may have 
concurrent hyperadrenocorticism, diabetes 
mellitus, excessive use of megestrol acetate or 
other progesterone compounds, or as a para  - 
neoplastic syndrome.
• A small number of cats have no biochemi-
cal alterations.
• Naturally occurring disease tends to be 
recognized in old cats.
• Iatrogenic cases have no age predilection.
SIGNS
• Gradual onset of clinical signs.
• Progressive alopecia (not always present).
• Often associated with weight loss, lusterless 
coat, poor appetite, and lack of energy.
• Skin becomes markedly thin and tears with 
normal handling.
• Skin rarely bleeds upon tearing.
• Multiple lacerations (both old and new) 
may be noted on close examination.
• Partial to complete alopecia of the truncal 
region may be noted.
• Sometimes associated with “rat tail,” pinnal 
folding, pot-belly appearance.
• Differentiated from cutaneous asthenia by 
lack of hyperextensibility.
• Hyperadrenocorticism—pituitary- or 
adrenal-dependent.
• Iatrogenic—secondary to excessive 
corticosteroid or progesterone drug 
• Diabetes mellitus—rare, unless associated 
• Possibly idiopathic or paraneoplastic 
syndrome.
  DIAGNOSIS
• Cutaneous asthenia.
• Feline paraneoplastic syndrome—pancre-
atic neoplasia, hepatic lipidosis, cholangio- 
carcinoma.CBC/BIOCHEMISTRY/URINALYSIS
• Little diagnostic significance in most cases.
• Approximately 80% of cats with hyper-
adrenocorticism have concurrent diabetes 
mellitus (hyperglycemia, glucosuria).
stimulation test—70% of cats with hyper-
adrenocorticism have an exaggerated 
response.
test—15–20% of normal cats may fail to 
decrease cortisol levels; typically unsuppressed 
with hyperadrenocorticism and nonadrenal 
illness.
• High-dose dexamethasone-suppression 
test—normal cats show decreases in cortisol 
concentrations; typically decreased with 
nonadrenal illnesses; considered by many 
clinicians to be the best screening test for 
hyperadrenocorticism; unreliable for 
discriminating between adrenal tumors and 
pituitary-dependent causes of hyperadreno-
corticism, because both conditions fail to 
show suppression.
• Endogenous ACTH levels—normal range 
for most labs is 20–100 pg/mL.
IMAGING
• Abdominal ultrasonography—adrenal 
masses are often small until end-stage disease; 
cholangiocarcinoma and hepatic lipidosis 
have been reported.
• CT and MRI—small pituitary tumors may 
be difficult to visualize; MRI may be more 
successful.
Histopathology—suggestive, not diagnostic; 
epidermis and dermis are thin; attenuated 
collagen fibers are evident.
  TREATMENT
• Underlying metabolic disease should be 
ruled out.
• Many patients are debilitated and require 
• Surgical correction of the lacerations—dif-
ficult because the tissue cannot withstand 
pressure from sutures.
• Protect skin—clothing; reduce activities 
that can traumatize the skin; remove sharp 
edges from the environment; prevent damage 
from interaction with other animals.
• Discontinue exogenous corticosteroids if 
• Hyperadrenocorticism—adrenalectomy is 
the preferred treatment.
• Cobalt-60 radiation therapy—variable 
success in the treatment of pituitary tumors.  MEDICATIONS
• Medical management—may be useful for 
preparing patient for surgery and for 
minimizing postoperative complications (e.g., 
infections and poor wound healing).
• No known effective medical therapy for 
feline hyperadrenocorticism.
• Mitotane (1,1-( o,p′-dichlorodiphenyl)-2,2-
dichloroethane [ o,p′-DDD]) 12.5–50 mg/kg 
PO q12h; response has been equivocal; side 
effects include anorexia, vomiting, and 
diarrhea.
• Metyrapone 65 mg/kg PO q12h; clinical 
improvement noted more often with this 
drug than the others.
Hyperadrenocorticism—closely monitor 
diabetic cats; adjust insulin to prevent 
hypoglycemia when the cortisol levels fall.
  FOLLOW-UP
Patients are often quite debilitated, making 
any form of treatment risky; close monitoring 
is required in all cases.
Gross TL, Ihrke PJ, Walder EJ. Veterinary 
Dermatopathology. Philadelphia, PA: 
Mosby, 1992.
Little SE. August’s Consultations in Feline 
Internal Medicine, Volume 7. Philadelphia, 
PA: Saunders, 2016.
systemic disease. J Feline Med Surg 2017, 
19(9): 948–960.
Resnick

S
1262  Blackwell’s Five-Minute Veterinary Consult  
SSmall Intestinal Dysbiosis
  BASICS
• Small intestinal dysbiosis (SID) is a clinical 
syndrome caused by an alteration of the small 
intestinal microbiota. • Previously, a variety of 
different terms have been used to describe SID: 
◦ Small intestinal bacterial overgrowth 
(SIBO)—defined as >104 anaerobic and/or 
>105 total bacterial cfu/mL in duodenal juice 
from dogs. However, these criteria are now 
controversial. ◦ Antibiotic-responsive diarrhea 
(ARD)—used by several authors to describe 
patients that have diarrhea that responds to 
antibiotic therapy. Neither the type of bacteria 
nor the type of antibiotic that is effective has 
been defined for ARD. ◦ Tylosin-responsive 
diarrhea (TRD)—used by a group of clinicians 
in Finland to describe several dogs with chronic 
diarrhea that failed to respond to a variety of 
antibiotics or corticosteroids, but did respond 
to treatment with tylosin. • Currently, there is 
no consensus on the quantitative makeup of 
the gastrointestinal microbiota in healthy dogs 
or cats. • Note that SID differs from colonization 
of the alimentary tract by known pathogenic 
bacteria (e.g., Salmonella  spp., Campylobacter 
jejuni , enterotoxigenic Clostridium perfringens , 
enterotoxic Escherichia coli , or others).
• Bacteria are constantly ingested with food 
and/or saliva. • Host-protective mechanisms 
prevent overgrowth of pathogenic or 
potentially pathogenic bacteria through 
gastric acid secretion, intestinal motility 
(peristalsis), secretion of antimicrobial 
substances in bile and pancreatic juice, and 
local enteric IgA production. • The ileocolic 
valve is a physiologic barrier between the large 
bowel, which is populated by large numbers 
of bacteria, and the less populated small 
bowel. • When these natural defense 
mechanisms fail and excessive numbers of 
certain bacterial species persist in the upper 
small intestine, they may cause pathology, 
even though they are not considered obligate 
pathogens. • Anaerobic bacteria (e.g., 
Bacteroides  spp. and Clostridium  spp.) have 
been considered more likely to cause 
pathology than many aerobic bacteria.
• Gastrointestinal—normal absorptive 
function is disrupted, resulting in loose stool 
and weight loss. • Hepatobiliary—portal vein 
carries bacterial toxins and other substances to 
the liver, which may lead to hepatic changes.
GENETICS
• No genetic basis for SID has been 
identified. However, recent studies would 
suggest that histiocytic ulcerative colitis 
should be considered a type of dysbiosis of 
the large intestine. Since the majority of 
cases have been described in the boxer, genetic factors that predispose dogs of this 
breed to this type of dysbiosis are likely. 
• Certain canine breeds (e.g., German 
shepherd dog, Chinese Shar-Pei, and beagle) 
appear to be at an increased risk for SID.
Unknown
N/A
Species
Subjectively, German shepherd dog, Chinese 
Shar-Pei, and beagle appear to have an 
increased incidence.
• Unknown. • Can be diagnosed in dogs and 
cats of any age (age range: <1 year to >8 
years).
SIGNS
Alterations in the gut microbiota can cause 
clinical signs of small intestinal disease, such 
as loose stool or diarrhea, weight loss, and/or 
others.
• Chronic loose stools or diarrhea (small 
bowel or large bowel type diarrhea)—
common. • Weight loss, despite a reasonable 
appetite—common. • Borborygmus and 
flatulence—common. • Vomiting—
occasional/variable. • Clinical signs of the 
underlying disease process may be seen in 
cases of secondary SID. • Clinical signs may 
wax and wane or be continuous.
Unremarkable or evidence of weight loss and 
decreased body condition.
CAUSES
• Primary SID is probably uncommon, but a 
definitive cause of SID often remains 
undiagnosed and thus many dogs are 
diagnosed with idiopathic SID. • Secondary 
SID (more common): ◦ Altered small 
intestinal anatomy—inherited or acquired 
(e.g., congenital blind loop, partial 
obstructions, neoplasia, foreign body, 
intussusception, stricture, adhesion, or 
diverticulum). ◦ Altered intestinal motility—
hypothyroidism, autonomic neuropathies. 
◦ Exocrine pancreatic insufficiency (EPI)—
approximately 70% of dogs with EPI have 
concurrent SID. ◦ Hypochlorhydria or 
achlorhydria—spontaneous or iatrogenic 
(e.g., proton pump inhibitor treatment). 
◦ Altered immune system—immuno -
deficiency, decreased mucosal defense, and 
preexisting intestinal disease.RISK FACTORS
Intestinal diseases that affect local defense 
mechanisms (e.g., inflammatory bowel disease 
[IBD], adverse food reactions, parasite 
infestation, others).
  DIAGNOSIS
• Secondary gastrointestinal disease (e.g., hepatic 
failure, renal failure, EPI, chronic pancreatitis, 
hypothyroidism, hypoadrenocorticism). 
• Primary gastrointestinal disease (i.e., 
mechanical, toxic, or other).
• Usually unremarkable. 
• Hypoalbuminemia—uncommon finding; 
when present, it suggests particularly severe 
intestinal disease and warrants an aggressive 
diagnostic and therapeutic approach.
Serum Cobalamin and Folate 
Concentrations
• Serum folate concentration may be 
increased, as many bacterial species synthesize 
folate and an increased abundance of folate- 
producing bacterial species will lead to an 
overabundance of folic acid in the small 
intestine. • Serum cobalamin concentration 
may be decreased, as many bacterial species 
compete with the host for dietary cobalamin. 
• The finding of an increased serum folate 
concentration and a decreased serum 
cobalamin concentration is suggestive, but 
not specific for SID in dogs. In addition, not 
all patients with SID show this pattern.
Qualitative and Quantitative Bacterial 
Culture of Small Intestinal Juice
• Aerobic and anaerobic quantitative culture of 
duodenal fluid has long been considered the 
“gold standard” for the diagnosis of SIBO in 
human patients. • Invasive—requires endoscopy 
or laparoscopy. Not practical and not routinely 
available. • Recent work would suggest the 
species of bacteria that comprise the small 
intestinal microbiota may be more important 
than bacterial numbers. • No standardized 
protocols have been established for sampling, 
handling, and culturing of duodenal juice, 
leading to high variability in bacterial counts.
Dysbiosis index (DI)
• The fecal DI is a PCR-based assay that 
quantifies the abundances of eight bacterial 
groups in fecal samples of dogs and summarizes 
them in one single number. • A DI below 0 
indicates a normal fecal microbiota; a DI above 
0 indicates dysbiosis. Approximately 15% of 
clinically healthy dogs have an increased DI, 
with most of them falling into the equivocal 
range between 0 and 2. • Many dogs with 
chronic enteropathy or EPI have an abnormal

Canine and Feline, Seventh Edition  1263
SSfecal DI. • Due to anatomical and physiological 
differences along the intestine, evaluation of the 
fecal DI may not accurately reflect microbiota 
changes in the small intestine. • Concurrent 
evaluation of serum concentration of cobalamin/  
folate with assessment of the fecal DI may help 
in the diagnosis of SID.
IMAGING
Not useful for the diagnosis of primary SID. 
However, may reveal findings indicative of an 
Therapeutic Trial
• T reatment of patients with suspected SID 
with an antibiotic, a prebiotic, or a probiotic. 
• Interpreting the results of a therapeutic trial 
may be difficult as more than one disease 
(e.g., IBD plus SID, dietary intolerance plus 
SID) may be present, and lack of a clinical 
response might lead to the incorrect 
conclusion that SID is absent; incorrect 
selection of the treatment that is trialed might 
also cause failure of a clinical response.
• No macroscopic findings upon exploratory 
laparotomy or endoscopy. • Histopathology 
of small intestinal mucosal biopsies is 
typically unremarkable unless SID is caused 
by underlying intestinal disease.
  TREATMENT
• Outpatient medical management. • SID 
can be managed with antibiotics, prebiotics, 
probiotics, or a combination thereof: 
◦ Antibiotics—see Medications. 
◦ Prebiotics—see Diet. ◦ Probiotics—there 
has been a lot of interest in probiotic use for 
dogs and cats with chronic diarrhea, although 
little is known about the efficacy. Currently, 
because of quality issues with many products, 
only probiotics from major manufacturers can 
be recommended. • Improvement may take a 
few days to several weeks.
• Usually none. • Supportive care for 
emaciated or hypoalbuminemic patients.
ACTIVITY
DIET
• Highly digestible diet. • A diet containing 
fructooligosaccharides has been shown to be 
beneficial in dogs with SID.
• Some patients show clinical improvement 
within days. • Some patients require weeks of 
therapy before demonstrating improvement—
treat for 2–3 weeks before concluding that therapy 
is ineffective. • Any concurrent or predisposing 
diseases (e.g., IBD, EPI, dietary intolerance/allergy, alimentary tract neoplasia, partial obstruction) 
must also be treated. • Continuous or repeated 
treatment is often required.
Only indicated for some underlying causes of 
SID (i.e., partial obstruction, diverticulum, or 
intestinal mass).
• Broad-spectrum, orally administered antibiotics 
effective against both aerobic and anaerobic 
bacteria are preferred. • Tylosin (10–20 mg/kg 
PO q12h for 6 weeks) is the primary choice. 
Tylosin is usually used in a powder formulation 
that is marketed for use in poultry and pigs. It 
is administered in the food because of its bitter 
taste. It can be used long-term and is very safe 
and inexpensive. For small dogs and cats the drug 
should be reformulated into capsules. For larger 
dogs the dose can be approximated by using a 
teaspoon and administering the drug in food. 
• Metronidazole (10–15 mg/kg PO q12h for 
6 weeks) is used commonly in routine 
practice because of its activity against 
anaerobic bacteria. Metronidazole may also 
have immunomodulatory effects. However, 
metronidazole can have significant side effects. 
• Dogs with SID may be cobalamin deficient, 
and parenteral or oral supplementation of 
vitamin B12 is indicated. See Cobalamin 
Deficiency for dosing information.
None
Metronidazole can be associated with gastro  - 
intestinal side effects and in rare cases with 
neurologic side effects.
None
In dogs with EPI and SID, concurrent 
therapy for SID is only indicated if enzyme 
replacement alone does not resolve the 
diarrhea and/or lead to weight gain.
  FOLLOW-UP
• Body weight and, in hypoproteinemic 
patients, serum albumin concentrations are 
the most important parameters; improvement 
suggests effective therapy. • Diarrhea should 
resolve. • If diarrhea persists despite improved 
body weight and/or increased serum albumin 
concentration, investigation for concurrent 
intestinal disease is indicated.
N/A
Primary SID without complicating factors 
(e.g., IBD, lymphoma) usually has a good 
prognosis, although relapses can be seen 
following cessation of antibiotic therapy.
• SID has been suspected as a cause of IBD 
in some patients. • EPI.
N/A
None
Avoid oxytetracycline or metronidazole, 
especially during early pregnancy.
SYNONYMS
SIBO, ARD, or TRD may be used 
synonymously by some authors.
SEE ALSO
• Cobalamin Deficiency. • Diarrhea, 
Chronic—Cats. • Diarrhea, Chronic—Dogs. 
• Exocrine Pancreatic Insufficiency. 
• Inflammatory Bowel Disease. 
• Lymphoma—Cats. • Lymphoma—Dogs.
• ARD = antibiotic responsive diarrhea. • DI 
= dysbiosis index. • EPI = exocrine pancreatic 
insufficiency. • IBD = inflammatory bowel 
disease. • SIBO = small intestinal bacterial 
overgrowth. • SID = small intestinal dysbiosis. 
• TRD = tylosin-responsive diarrhea.
www.vetmed.tamu.edu/gilab
Intern Med 2003, 17(1):33–43.
Kilpinen S, Spillmann T, Westermarck E. 
Efficacy of two low-dose oral tylosin regimens 
in controlling the relapse of diarrhea in dogs 
with tylosin-responsive diarrhea: a prospective, 
single-blinded, two-arm parallel, clinical field 
trial. Acta Vet Scand 2014, 66:43.
Suchodolski JS. Diagnosis and interpretation 
of intestinal dysbiosis in dogs and cats. Vet J 
2016, 215:30–37.
Authors  Jan S. Suchodolski and Jörg M. Steiner
available online(continued)  Small Intestinal Dysbiosis

1264  Blackwell’s Five-Minute Veterinary Consult  
SSmoke Inhalation
  BASICS
OVERVIEW
• Injury secondary to direct heat damage to 
upper airway and nasal mucosa. Inhalation 
of toxins directly irritates the airway, and 
particulate matter adheres to the airways 
and alveoli. • Carbon monoxide decreases 
tissue oxygen delivery by preferentially 
binding to hemoglobin. • Cyanide 
interferes with oxygen usage in oxidative 
phosphorylation. • Extent of damage 
depends on the degree and duration of 
exposure and the material that was burning. 
• Serious lung injury possible with little 
external evidence of burning. • Lung 
reaction—initially bronchoconstriction, 
airway edema, mucus production and 
airway occlusion; then an inflammatory 
response, necrotizing tracheobronchitis, and 
pulmonary fluid accumulation due to 
increased capillary permeability. • Lung 
dysfunction typically progresses during 
initial 2–3 days. • Secondary bacterial 
infections—common cause of morbidity 
late in the disease.
SIGNS
• Historical findings consistent with 
exposure. • Smoky odor. • Tachypnea and 
increased respiratory effort. • Inspiratory 
effort suggests upper airway obstruction by 
edema. • Postural adaptations to hypoxemia. 
• Mucous membranes can be cherry red 
(from carboxyhemoglobin), pale, or cyanotic. 
• Auscultation of wheezes, harsh broncho­
vesicular sounds, or crackles. • Cough. 
• Burns, shriveled whiskers, conjunctival 
edema, corneal ulcers. • Neurologic signs 
indicate carbon monoxide or cyanide toxicity. 
• Cardiac arrhythmias and hypotension can 
be seen secondary to hypoxemia, smoke and 
carbon monoxide inhalation, and burn injuries.
Exposure to smoke, usually from being 
trapped in a burning building.
  DIAGNOSIS
• Neutropenia—poor prognostic sign; 
suggests neutrophil sequestration in the lungs. 
• Thrombocytopenia—suggests platelet 
sequestration or consumption. 
• Biochemistry profile—evidence of hypoxic 
damage to other organ systems can be 
present.IMAGING
Thoracic radiographs—establish a baseline; 
findings vary from normal to a broncho­
interstitial or alveolar pattern.
• Bronchoalveolar lavage/endotracheal wash 
if suspected secondary bacterial infection: 
culture; cytology—acute suppurative reaction 
with excessive mucus, neutrophils, and 
alveolar macrophages; intracellular bacteria 
indicate concurrent infection. • Arterial 
blood gas to confirm hypoxemia. Pulse 
oximetry difficult to interpret as carboxy­
hemoglobin falsely increases values. 
Co­oximetry showing carboxyhemoglobin 
levels >15% indicates toxicity. 
• Bronchoscopy demonstrates severity of 
airway damage, and is used to remove foreign 
particles and accumulated secretions.
  TREATMENT
• Initial management—stabilize respiratory 
function; establish patent airway; severe upper 
airway edema or obstruction can require 
intubation or temporary tracheostomy. 
• Oxygen—administer immediately to 
displace carbon monoxide from hemoglobin; 
use the highest available concentration for 2–4 
hours (or longer); after elimination of 
carboxyhemoglobin, supplement as needed. 
• Fluid therapy—crystalloid fluid 
resuscitation as needed to maintain perfusion 
with care to avoid fluid overload and 
progressive pulmonary edema. Associated 
burns can result in significant fluid and 
protein losses which may also require 
concurrent colloidal support (synthetic, 
albumin, plasma). • Nebulization of saline—  
moistens airway secretions to facilitate 
clearance. • Mechanical ventilation needed in 
severe cases. • Nutritional support—maintain 
body condition and immune status.
• Suspected bacterial infection—broad ­
spectrum antibiotics, ideally after bacterial 
culture has been obtained. • Bronchodilators—  
improve respiratory function if severe 
bronchoconstriction, especially cats (e.g., 
terbutaline 0.01 mg/kg IV, IM, SC). Inhaled 
beta­agonists can also be beneficial. 
• Corticosteroids—controversial, single early, 
anti­inflammatory dose or aerosolized 
corticosteroids may decrease airway edema. 
• Analgesia—as required for associated 
discomfort. Avoid oversedation due to 
decreased respiratory drive.CONTRAINDICATIONS/POSSIBLE 
• Diuretics—decrease IV volume without a 
major beneficial effect. • Corticosteroids—
use only once and if absolutely necessary; can 
predispose the patient to bacterial infection.
  FOLLOW-UP
• Respiratory rate and effort, mucous 
membrane color, heart rate, pulse quality, lung 
auscultations, and packed cell volume/total 
solids for 24–72 hours. • Repeat radiographs 
in 72 hours—ensure condition is resolving; 
monitor for bacterial pneumonia. • Pulse 
oximetry and arterial blood gas analysis—to 
monitor hypoxemia and response to therapy.
• Bacterial tracheobronchitis or pneumonia. 
• Profound pulmonary inflammatory 
response or severe systemic inflammatory 
response syndrome may result in acute 
respiratory response syndrome. Bronchiectasis 
can develop secondary to airway injury and 
impaired mucociliary clearance. • Carbon 
monoxide toxicity may lead to acute and 
delayed neurologic signs including seizures, 
cerebral edema, ataxia, paresis, and changes in 
mental status.
• Good if responding to treatment—likely to 
worsen prior to improving. Prognosis declines 
if complications occur. • Severe burns or organ 
injury—poor prognosis.
Berent AC, Todd J, Sergeeff J, Powell LL. 
Carbon monoxide toxicity: a case series. J 
Vet Emerg Crit Care 2005, 15(2):128–135.
Fitzgerald KT, Flood AA. Smoke inhalation. 
Clin Tech Small Anim Pract 2006, 
21(4):205–214.
Mariani CL. Full recovery following delayed 
neurologic signs after smoke inhalation in a 
dog. J Vet Emerg Crit Care 2003, 
13(4):235–239.
injury in small animals. Part 2: diagnosis, 
G. King.

Canine and Feline, Seventh Edition  1265
SSnake Venom Toxicosis—Coral Snakes
  BASICS
OVERVIEW
• T wo clinically important species in North 
America— Micrurus fulvius , eastern coral 
snake (North Carolina to the north; southern 
Florida to the south; west of the Mississippi 
River) and Micrurus tenere , Texas coral snake 
(west of Mississippi; in Arkansas, Louisiana, 
and Texas).
• Family Elapidae—fixed front fangs.
• Color pattern—bands fully encircling the 
body; red, yellow, and black; distinguished 
from the harmless tricolored king snake 
(Lampropeltis elapsoides ) by the arrangement 
of the bands: if yellow (caution) and red 
(danger) color bands touch, then stay clear; 
relatively small head; black snout; round 
pupils.
Bites
• Relatively uncommon due to snake’s 
reclusive behavior and nocturnal habits.
• Often occur on the lip. Snakes remain 
attached due to chewing action.
• Distinct fang marks may not be obvious.
• Primary cause of death—respiratory 
collapse.
SIGNS
• Onset of clinical signs may be delayed 
several hours (up to 18 hours).
• Localized signs generally absent.
• Generalized weakness and ataxia.
• Bulbar paralysis—affecting cranial motor 
nerves, respiratory tract, and skeletal muscles; 
acute flaccid quadriplegia.
• Salivation—caused by dysphagia.
• Dyspnea.
• Hyporeflexive spinal reflexes.
• Urinary incontinence.
• Size of the snake.
• Size and duration of bite.
  DIAGNOSIS
• Myasthenia gravis.
• Tick bite paralysis.
• Black widow spider bite ( Latrodectus  spp.).
• Hemolysis—dogs only.
• Red blood cell burring.
• May note high creatine kinase.• Hemoglobinuria—dogs only.
N/A
N/A
  TREATMENT
• First aid—generally avoid; most effective 
measure is rapid transport to a veterinary 
facility for antivenom administration; 
Australian technique for elapid bites is a 
pressure wrap of the bitten limb with ace-type 
bandage to decrease blood flow and venom 
uptake.
• Caution : do not wait for onset of clinical 
signs to initiate treatment.
• Inpatient—hospitalize for a minimum of 
48 hours.
• Monitor CNS and respiratory function 
closely for 24 hours.
• Specific antivenin is extremely limited for 
M. fulvius  envenomations in the United States 
and typically not accessible for veterinary use. 
However, protective crossreactivity occurs 
with the following antivenins: Coralmyn 
(Fab2 equine origin) (Instituto Bioclon, 
Mexico), Costa Rican coral snake antivenin 
(Instituto Clodomiro Picado, Costa Rica), and 
Australian tiger snake Notechis scutatus  (CSL 
Limited, Parkville, Victoria, Australia). 
Expense may be a consideration. Local zoos 
may have antivenom available. Application for 
an INR permit from the US Department of 
Agriculture may allow a veterinary hospital to 
acquire these antivenoms.
• If antivenin unavailable—provide 
ventilatory support for several days in a 
critical care facility.
• M. fulvius  reactive antivenin (see 
T reatment)—indicated if the history includes 
recent coral snake interaction; evidence of 
puncture wounds; clinical signs consistent 
with coral snake envenomation; administer 
1–2 vials; additional vials may be necessary 
(technique same as for pit viper antivenin).
• Broad-spectrum antibiotics are not 
routinely recommended and should only be 
used if there is indication of infection.
• Neostigmine – may be useful to reverse 
neuromuscular blockade if antivenin not 
available. Has been used successfully to treat 
M. frontalis  envenomation in Brazil.
• Corticosteroids—not indicated.• Observe precautions outlined for pit viper 
antivenin administration (see Snake Venom 
Toxicosis—Pit Vipers).
  FOLLOW-UP
• Marked clinical signs may last 1–1.5 weeks.
• Full recovery may take months as receptors 
regenerate.
SEE ALSO
Snake Venom Toxicosis—Pit Vipers.
Pérez ML, Fox K, Schaer M. A retrospective 
evaluation of coral snake envenomation in 
dogs and cats: 20 cases (1996–2011). J Vet 
Emerg Crit Care 2012, 22(6):682–689.
Pérez ML, Fox KJ, Schaer MA. Retrospective 
review of coral snake envenomation in the 
dog and cat: 20 cases 1996 to 2011. 
Toxicon 2013, 60(2):247–248.
Peterson ME. Snake bite: Coral snakes. In: 
Animal Toxicology, 3rd ed. St. Louis, MO: 
Saunders, 2013, pp. 799–805.
Author  Michael E. Peterson

1266  Blackwell’s Five-Minute Veterinary Consult  
SSnake Venom Toxicosis—Pit Vipers
  BASICS
OVERVIEW
• Pit vipers— Crotalus  spp. (rattlesnakes), 
Sistrurus  spp. (pigmy rattlesnakes and 
massasauga), and Agkistrodon  spp. (copperheads 
and cottonmouth water moccasins); retractable 
fangs; heat-sensing pit between the nostril and 
eye; triangle-shaped head.
• Range—throughout the United States (not 
found in Alaska, Hawaii, Maine).
• Toxicity—considered hemotoxic; several 
species have subpopulations with lethal 
neurotoxic components (e.g., Mohave 
rattlesnake); general ranking of severity: (1) 
rattlesnakes, (2) moccasins, (3) copperheads.
• Venom—enzymes: hyaluronidase and 
phospholipase A (cause local tissue injury) 
and others that interfere with the coagulation 
cascade (cause major coagulation defects); 
non-enzymatic polypeptides: affect the 
cardiovascular and respiratory systems.
• Bite—80% of victims have altered 
laboratory values and clinically important 
swelling; severe hypotension from pooling of 
blood within the splanchnic (dogs) or 
pulmonary (cats) vessels; fluid loss from the 
vascular compartment secondary to severe 
peripheral edema.
• Approximately 20% crotalid bites 
considered “dry bites” with little if any venom 
deposited and no associated toxicity.
• Behavioral—usually related to pain.
• Cardiovascular—lower blood pressure, 
direct cardiotoxins (Eastern and Western 
Diamondback rattlesnake venom).
• Gastrointestinal—nausea, diarrhea.
• Hematologic—coagulopathies (hyperco-
agulation or consumptive), 
• Musculoskeletal—rhabdomyolysis.
• Nervous—multiple crotalid species have 
individuals with venom containing Mojave 
toxin, a potent neurotoxin.
• Skin—puncture wounds possible local 
tissue necrosis.
SIGNS
May be delayed for 8 hours after 
• Outdoors, rural setting, indigenous snake.
• Owner saw bite or heard snake.
• Puncture wounds on head and forelimbs in 
most animals.• Local tissue swelling and pain surrounding 
bite site.
• Bruising, with possible necrosis and 
sloughing of bite site tissue.
• Ecchymosis and petechiation of tissues and 
• Hypotension and shock.
• Shallow respiration.
• Depression, lethargy, and muscle weakness.
• Nausea and excessive salivation.
Outdoor activity.
Snake-Associated
• Toxic peptide fraction: enzyme fraction 
ratio—higher in spring and lower in fall 
(not well documented); high in very young 
snakes.
• Amount of venom production since last 
bite.
• Size, fang length, aggressiveness, and 
motivation of snake.
Victim-Associated
• Bite site—bites to tongue and torso are of 
major concern.
• Size of victim.
• Elapsed time between bite and initiation of 
• Activity level of victim after the bite—activ-
ity increases absorption of venom.
  DIAGNOSIS
• Angioedema secondary to insect envenoma-
tion (spider, scorpion, large centipede).
• Blunt trauma.
• Penetrating wound.
• Animal bite.
• Penetration of foreign body.
• Draining abscess.
• Frequent burring of red blood cells within 
first 24 hours (echinocytes).
• Elevated creatine kinase.
• Hematuria or myoglobinuria.
Clotting tests—reduced platelets and 
fibrinogen, monitor for prolonged activated 
clotting time, prothrombin time, and partial 
thromboplastin time; may note elevated 
fibrin degradation products.
• Clinical evaluation of bite for edema, 
ecchymosis, fang punctures, pain.
• Electrocardiogram—may detect ventricular 
arrhythmia, especially in severely depressed 
patients.PATHOLOGIC FINDINGS
• Puncture wounds.
• Tissue necrosis.
• Hemorrhage, petechiation, ecchymosis.
• Pulmonary hemorrhage, edema.
  TREATMENT
• Tissue reaction around the bite site—not a 
reliable indicator of systemic toxicity.
• Bite location—may affect uptake of venom; 
bites to tongue and torso are of major 
concern. Distal limb bites may result in 
significant tissue damage and compromise 
limb function.
• First aid measures—minimize activity, calm 
patient, provide analgesia if indicated; 
transport quickly to a veterinary facility.
• Swelling can be objectively monitored with 
circumferential measurements using a cloth 
or flexible tape measure.
• Antivenom is only proven specific treatment 
(see Medications). Expense may be an important 
factor.
• IV fluids—correct hypotension.
• Analgesics to reduce pain and stress.
• Antibiotics—infection is rare and antibiot-
ics are not recommended unless there is 
evidence of infection.
• Repeat coagulation profile after 
administration of antivenom for comparison 
to earlier labs (typically the author performs 
on entry, 6 hours and 12 hours unless patient 
is obviously worsening). Recurrence of 
clinical signs or coagulation abnormalities can 
occur with any antivenin. This usually 
happens when initial coagulopathy is more 
severe. If initial coagulopathy resolved with 
antivenin administration, recurrence can 
occur within the next few days, although 
rarely as severe as initial. There are no 
documented cases of clinical bleeding with 
subsequent coagulopathy; however, the 
clinician should be aware of the possibility.
Activity
Initially restrict exercise as this can increase 
uptake of venom, once envenomation 
syndrome under control—activity as the 
patient will tolerate.
• Monitor patient for ecchymosis or 
petechiation.
• Monitor for evidence of serum sickness.
Antivenom
• Always flush antivenom vial after initial 
removal of antivenom, second flush can 
increase antibody collection by 30%.

Canine and Feline, Seventh Edition  1267
S• Allergic reaction—stop antivenom; give 
diphenhydramine; after 5 minutes, restart 
antivenom infusion at a slower rate.
• Mix each vial of antivenom with 100–150 
mL of a crystalloid fluid and administer IV 
slowly while taking into consideration the 
patient’s weight and overall fluid load. Infuse 
over 30 minutes–1 hour.
• Carefully monitor the inner pinna for onset 
of hyperemia (indicator of possible allergic 
reaction).
• With the exception of Crofabtm all anti  - 
venoms have approximately 20% of their 
protein content as actual antibodies against 
snake venom.
• Frequent administration of antivenom 
controls the animal’s pain.
• Other analgesics as needed to control pain.
Veterinary Licensed
• VenomVetTM (Crotalidae polyvalent, equine 
origin, Fab2). Injectable solution, no need to 
reconstitute. T wo South American immuniz-
ing snake species.
• AntiveninTM (Crotalidae polyvalent, equine 
origin, whole IgG—Boehringer-Ingelheim), 
reactions more common due to extraneous 
proteins. Lyophilized. T wo North American 
snake species and two South American species 
immunizing snake species.
• Rattler AntiveninTM (polyvalent, equine 
origin, whole IgG—Mg Biologics) equine 
plasma product, frozen. Four North 
American immunizing snakes.
FDA Licensed but Published Studies 
in Dogs
• Crofab® (polyvalent, ovine Fab1—BTG 
International) first prospective clinical trial of 
antivenom in dogs. Purified antibody 
fragments provide much less possibility for 
reactions. 99% protein is Fab1 antibodies 
against snake venom.
• Antivipmyn® (polyvalent, equine Fab2—Rare 
Disease Therapeutics) has completed safety and clinical trials in dogs. Purified antibody 
particles much less possibility for reactions.
• Caution : in animals receiving beta-blockers, 
the onset of anaphylaxis may be masked; 
therefore, the condition may be more 
advanced once recognized and more difficult 
to treat effectively.
• Corticosteroids—of no value.
• Dimethyl sulfoxide (DMSO)—enhances 
uptake and spread of venom.
• Heparin—do not use; not effective against 
thrombin-like enzymes and worsens coagulo- 
pathies.
Rattlesnake vaccine for dogs is currently 
marketed. Its efficacy is unknown, but several 
published papers have shown mixed results; 
only anecdotal evidence at this time. Not 
recommended until peer-reviewed efficacy 
data available.
  FOLLOW-UP
• Repeated laboratory analysis—6 hours after 
admission to hospital.
• Clinical signs—may last 1–1.5 weeks.
• Once released, owner should monitor for 
recurrence of coagulopathies or delayed serum 
sickness.
• None unless underlying pathology 
(e.g. renal disease).
• Patients receiving other medications (e.g. 
nonsteroidal anti-inflammatory drugs).PREGNANCY/FERTILITY/BREEDING
• Antivenom has been given to pregnant 
animals and humans with no adverse events.
• Pregnancy is at risk from venom effects 
upon placenta and fetal tissue.
App: Snakebite911 ER
Hoose JA, Carr A. Retrospective analysis of 
clinical findings and outcome of cats with 
suspected rattlesnake envenomation in 
Southern California: 18 cases (2007–2010). 
J Vet Emerg Crit Care 2013, 
23(3):314–320.
Julius TM, Kaelble MK, Leech EB, et al. 
Retrospective evaluation of neurotoxic 
rattlesnake envenomation in dogs and cats: 
34 cases (2005–2010). J Vet Emerg Crit 
Care 2012, 22(4):460–469.
Peterson ME, Matz M, Seibold K, et al. A 
randomized multicenter trial of Crotalidae 
polyvalent immune Fab antivenom for the 
treatment of rattlesnake envenomation in 
dogs. J Vet Emerg Crit Care 2011, 
21(4);335–345.
Pritchard JC, Birkenheuer AJ, Hanel RM, 
et al. Copperhead ( Agkistrodon contortrix ) 
envenomation of dogs: 52 cases (2004–
2011). J Am Anim Hosp Assoc 2014, 
online 6131, doi 10.5326.
Witsil AJ, Wells R, Woods C, Rao S. 272 
cases of rattlesnake envenomation in dogs: 
demographics and treatment including 
safety of F(ab ′)2 antivenom use in 236 
patients. Toxicon 2015, 105:19–26.
Woods C, Young D. Clinical safety 
evaluation of F(ab ′)₂ antivenom ( Crotalus 
durissus -Bothrops asper ) administration in 
21(5):565–569.
Consulting Editor  Lynn R. Hovda(continued)  Snake Venom Toxicosis—Pit Vipers

1268  Blackwell’s Five-Minute Veterinary Consult  
SSneezing, Reverse Sneezing, Gagging
  BASICS
• Sneezing—a normal, protective, expiratory 
reflex that serves to expel air and material 
from the lungs through the nasal cavity and 
mouth.
• Reverse sneezing—a normal protective, 
repetitive inspiratory reflex that serves to 
remove irritants from the nasopharynx (also 
termed the aspiration reflex).
• Gagging—a normal protective reflex to 
clear secretions from the larynx, trachea, 
pharynx, or esophagus. Prevents irritating/
toxic material from entering these 
structures; often misinterpreted as 
vomiting by owners.
• Irritation of submucosal irritant 
receptors; various stimuli (infectious, 
parasitic, irritant, mechanical—especially 
accumulated secretions) will elicit these 
reflexes depending on where the irritation 
is applied.
• Sneezing—nasal mucosal irritation; 
improves with chronicity.
• Reverse sneezing—caudodorsal 
nasopharyngeal mucosal irritation triggers 
pharyngeal muscle spasms, subsequent 
laryngeal obstruction and movement of 
material into the oropharynx.
• Gagging—intraoral stimulation (tracheal, 
laryngeal, oropharyngeal, potentially 
esophageal mucosal irritation) detected by 
afferent limb of gag reflex. Efferent limb gives 
rise to uncoordinated muscle movement 
characteristic of gagging.
• Respiratory—frequently associated with 
infectious or inflammatory conditions 
involving the upper respiratory tract.
• Gastrointestinal—gagging may also be 
caused by swallowing, esophageal, or gastric 
GENETICS
N/A
These are common, normal reflexes in both 
dogs and cats in response to mucosal 
irritation.
Worldwide
• Any dog or cat may be affected.
• These reflexes associated with the 
conditions that cause them; examples include:
◦ Young animals—infection, congenital 
defects (cleft palate0, primary ciliary 
◦ Older animals—nasal tumors, dental 
disease.• Acute sneezing in dogs is most often caused 
by a nasal foreign body, while in cats it is 
most often associated with acute viral rhinitis.
SIGNS
• Head and mouth position may help owners 
determine which of these reflexes are present.
• Sneezing typically results in sudden, 
explosive expiratory effort(s) with the mouth 
closed and head thrown downward; may 
result in the animal’s nose hitting the ground.
• Reverse sneezing is a sudden, often 
paroxysmal, noisy, inspiratory effort with the 
head pulled back, mouth closed, and lips 
sucked in.
• Gagging is an expiratory effort; typically, 
with the head and neck extended and mouth 
held open; usually ends with the animal 
swallowing (with little to nothing expelled).
• Nasal discharge commonly seen with 
sneezing and reverse sneezing. Retching, 
coughing and vomiting may accompany 
gagging.
CAUSES
• Any mucosal irritation or inflammation can 
elicit these airway reflexes. The reflex localizes 
the site of irritation for further evaluation.
• Nasal causes of sneezing and reverse 
sneezing include excess nasal secretions, 
rhinitis (idiopathic, secondary bacterial, viral 
or mycotic infections), foreign body, 
non-neoplastic masses (nasopharyngeal 
polyps, inflammatory polyps of the nasal 
turbinates), neoplasia, and parasites; dogs— 
Pneumonyssoides ; dogs and cats— Cuterebra , 
Eucoleus  (Capillaria ), Linguatula .
• Extranasal diseases resulting in reverse 
sneezing, sneezing and gagging—
pneumonia, esophageal strictures, 
megaesophagus, chronic vomiting, 
cricopharyngeal disorders, dental disease 
(oronasal fistulas, tooth root abscess).
• Reverse sneezing may be idiopathic, 
especially in small-breed dogs with no other 
associated clinical signs.
• Causes of gagging include:
◦ Secretions being coughed up from the 
lower airways and into the larynx or cervical 
trachea.
◦ Pharyngeal/laryngeal dysfunction 
resulting in airway aspiration due to loss of 
motor and/or sensory function that 
normally protects the airway.
◦ Vomiting from esophageal and gastro -
• Brachycephalic and dolichocephalic breeds 
• Incompletely or unvaccinated animals are at 
a higher risk of developing infection.
• Outdoor animals, especially hunting dogs, 
perhaps more at risk for nasal foreign bodies 
and nasal infections.
• Chronic dental disease can cause rhinitis 
and either sneezing or reverse sneezing.• Environmental factors like dusty areas, 
smoke inhalation, perfumes, cold air.
• Productive coughing may produce excess 
secretions that can be propelled into the 
nasopharynx and lead to reverse sneezing.
• Nasal mites may cause both reverse sneezing 
and sneezing in dogs (but not cats); in the 
United States, incidence is inversely 
proportional to heartworm preventive usage.
• Reverse sneezing is often associated with 
  DIAGNOSIS
• Differentiate regular sneezing (occurs on 
expiration) from reverse sneezing (occurs on 
inspiration and localizes the site of irritation 
to the nasopharynx).
• Gagging is often misinterpreted as 
vomiting.
Nonspecific for any cause of sneezing, reverse 
sneezing, or gagging. Identifies comorbidities.
Virus isolation, culture or PCR for upper 
respiratory tract infections (FCV, FHV-1, 
feline and canine influenza); retroviral testing 
(FeLV, FIV); cryptococcal antigen testing; 
Aspergillosis  testing; bacterial cultures 
(Mycoplasma  spp., Bordetella bronchiseptica ); 
cytology, histopathology and coagulation 
studies if indicated.
IMAGING
• Sneezing and reverse sneezing—skull 
radiographs, CT/MRI.
• Gagging—thoracic radiographs, fluoroscopy 
(dynamic swallow study), CT/ MRI.
• Sneezing and reverse sneezing—antegrade 
and retrograde rhinoscopy, nasal biopsy 
(histopathology), nasal culture (deep nasal 
flush sample), periodontal probing.
• Gagging—neurologic examination (CN 
V, IX, X, XII), sedated oropharyngeal exam, 
transtracheal wash, or bronchoalveolar 
lavage.
Nonspecific inflammation can be found in 
the nasal cavity or nasopharynx.
  TREATMENT
Removal of the inciting mucosal irritation, 
where/when possible, will result in relief from 
these reflexes.

Canine and Feline, Seventh Edition  1269
Outpatient therapy generally indicated, 
except perhaps following rhinoscopic biopsy.
ACTIVITY
Exercise and activity should be restricted after 
rhinoscopic biopsies to prevent excessive 
bleeding.
DIET
N/A
• Educate clients so they understand these are 
normal reflexes. Diagnostic testing is required 
to determine the underlying cause and to 
allow appropriate treatment.
• Close contact with other animals should be 
limited until treatment for the underlying 
cause (if infectious) is completed.
• Episodes of paroxysmal reverse sneezing 
may be lessened by inducing swallowing 
(rubbing the throat, giving water) or breath 
holding (cover nose and mouth).
• Anesthesia for surgery or endoscopy—
abscessed tooth, foreign body, masses or 
anatomical airway abnormality, treatment of 
fungal infections.
• Use surgery for laryngeal disease with 
caution when gagging is prominent due to an 
increased risk of aspiration pneumonia when 
concurrent esophageal dysfunction is present.
• There is no drug that specifically suppresses 
these reflexes; treatment is directed at the 
underlying irritant.
• Nasal bacterial infections best treated with 
antibiotics directed against Gram-positive 
bacteria (most common). Fungal disease 
treated with systemic and local infusion of 
antifungals.
• Nasal mites are treated with ivermectin 
200–300 μg/kg PO or SC weekly for 3 weeks, 
selamectin 6–24 mg/kg applied topically 
every 2 weeks for 3 doses, or milbemycin (in 
collies and similar breeds) 0.5–1 mg/kg PO 
weekly for 3 weeks. All dogs in the household 
should be treated to prevent reinfection.
• When no underlying nasal condition is found 
to explain sneezing, nasal mite treatment is 
recommended. Immunomodulatory antibiotics 
such as doxycycline 5–10 mg/kg PO q12–24h and azathioprine 1–2 mg/kg/day PO in 
combination with piroxicam 0.3 mg/kg PO 
daily may be considered.
• Lower airway diseases with excess secretions 
are treated with antibiotics if bacterial 
infection is confirmed; Gram-negative 
bacteria are most common.
• Anti-inflammatory—prednisolone 1–2 mg/
kg q12–24h or piroxicam 0.3 mg/kg PO 
q24–48h if no infection, for nonspecific 
airway inflammation.
• No treatment for gagging secondary to 
sensory loss in the larynx with recurring 
aspiration; elevation of food and water bowls 
is recommended. Altering the consistency of 
food offered may also be helpful.
• Ivermectin in collies and similar breeds 
(MDR1  gene mutation).
• Use of piroxicam concurrently with other 
nonsteroidal anti-inflammatory drugs or 
corticosteroids, as well as in patients with 
N/A
• Topical decongestants— 0.125% 
phenylephrine or 0.025% oxymetazoline.
• Antihistamines (diphenhydramine, Zyrtec, 
Claritin) may reduce secretions and sneezing 
in some cases with underlying allergic 
  FOLLOW-UP
Expect reduction in sneezing/reverse sneezing 
with appropriate therapy.
Limit access to foreign bodies, provide 
adequate dental care and appropriate 
If gagging is secondary to laryngeal sensory 
loss, serious aspiration pneumonia may 
develop.
• Nasal mites should respond to treatment 
within 3 weeks.• Sneezing and reverse sneezing secondary to 
foreign material resolve quickly after removal 
of the foreign body.
• Neoplasia may carry a poorer prognosis 
(chemotherapy or radiation therapy may be 
N/A
N/A
Rare; immunocompromised individuals at 
greater risk with infectious causes.
N/A
SEE ALSO
Demko JL, Cohn LA. Chronic nasal 
discharge in cats: 75 cases (1993–2004). J 
Am Vet Med Assoc 2007, 230:1032–1037.
Doust R, Sullivan M. Nasal discharge, 
sneezing and reverse sneezing. In: King LG, 
ed., Textbook of Respiratory Disease in 
Dogs and Cats. Philadelphia, PA: Saunders, 
2004, pp. 17–29.
Kook P . Gagging. In: Ettinger SJ, Feldman 
EC, eds., Textbook of Veterinary Internal 
Medicine, 6th ed. St. Louis, MO: Saunders, 
2005, pp. 152–155.
Louis, MO: Saunders, 2005, pp. 111–115.
Plickert HD, Tichy A, Hirt RA. 
Characteristics of canine nasal discharge 
related to intranasal diseases: a retrospective 
study of 105 cases. J Small Anim Pract 
2014, 55:145–152.
Author  Jonjo Reece
Dominique Peeters and Brendan C. 
McKiernan. 
available online(continued)  Sneezing, Reverse Sneezing, Gagging

1270  Blackwell’s Five-Minute Veterinary Consult  
SSoft Tissue Sarcoma
  BASICS
• A mesenchymal neoplasm arising within or 
from connective tissues. • T umors in this 
heterogeneous group have different histologic 
origins yet demonstrate similar pathologic 
features and clinical behavior, and include 
fibrosarcoma, leiomyosarcoma, peripheral 
nerve sheath tumor, and myxosarcoma. 
Histology reports may commit only to soft 
tissue arcoma (STS) or spindle cell sarcoma, 
and may not distinguish among cell of origin 
without immunohistochemistry. • Because of 
divergent pathogenesis and biologic behavior, 
this group of tumors does not include 
hemangiosarcoma and other tumors that 
sometimes share the suffix (for example 
melanosarcoma, osteosarcoma, or lympho­
sarcoma). Histiocytic sarcoma is also 
considered separately.
• T umors can arise in connective tissues in 
any anatomic location. • Locally invasive 
behavior is typical with tumor extension 
beyond gross visible margins. • T umors often 
have low (<20%, low grade/grades 1–2) to 
moderate (40–50%, high grade/grade 3) 
metastatic potential. • T umors can develop at 
sites of chronic inflammation such as 
following ocular trauma or injection sites 
(cats). Also in vaccine ­induced sarcomas in 
cats, the aluminum adjuvant may have 
inflammation ­independent carcinogenic 
effects.
• Skin—most commonly arise from skin or 
subcutis. • Musculoskeletal—from muscle, 
fascial and fibrous tissues. • Nervous—
originate from neurovascular structures. 
• Respiratory—STS metastasize hemato­
genously, with predilection for pulmonary 
metastases development in advance disease 
stages. • Lymphatic—regional lymph nodes 
are rare sites of metastasis.
GENETICS
There are no specific breed predilections that 
would suggest genetic predisposition.
• STS constitute 7% and 15% of skin and 
subcutaneous tumors in the cat and dog, 
respectively. • Incidence annually around 17 
per 100,000 cats at risk; 35 per 100,000 dogs 
at risk.
Species
All including the dog and cat.
None identified but large ­breed dogs are 
often overrepresented.Mean Age and Range
• Dogs—middle ­aged, range 2–15 years. 
An exception is rhabdomyosarcoma of the 
bladder that often arises in younger dogs. 
• Cats—middle ­aged, range 1.4–18.8 years.
SIGNS
• Rate of growth often reflects grade (low 
grade = slow ­growing; high grade = rapid). 
• Typically nonpainful, fluctuant to firm 
mass. • Signs depend on location and local 
structures affected by tumor presence or 
invasion. • T umors arising in the abdomen 
may elicit signs due to compression of the 
gastrointestinal tract and could include 
vomiting and/or diarrhea, anorexia, and 
weight loss. Additionally signs of intestinal 
obstruction and occasionally perforation can 
occur with gastrointestinal leiomyosarcoma. 
• Urinary signs of hematuria and dysuria may 
be seen in young dogs with bladder rhabdomyo­
sarcoma. • Peripheral nerve sheath tumors 
affecting the brachial or lumbosacral plexus 
can cause signs of lameness and pain, muscle 
atrophy, limb weakness progressing to 
paralysis. • Signs of hypoglycemia (paraneo­
plastic) such as weakness, collapse, and 
seizures can occur with leiomyoma or 
• Soft tissue mass that is soft, fluctuant, or 
firm on palpation. • Often adhered to 
underlying tissue. • Nonpainful unless 
ulcerated or invading into muscles or nerves.
CAUSES
• Dogs —STS have been documented 
following radiation therapy, trauma, 
orthopedic implants, foreign bodies, and the 
parasite Spirocerca lupi  (esophageal sarcoma). 
• Cats—See Pathophysiology.
  DIAGNOSIS
• Abscess. • Other cutaneous tumors, both 
benign and malignant (lipoma, basal cell 
tumors, mast cell tumors). • Fungal 
• Usually normal. • Hypoglycemia in dogs with 
leiomyoma or leiomyosarcoma (paraneoplastic 
syndrome mediated primarily by insulin ­like 
growth factors produced by tumor).
• Three ­view thoracic radiographs are 
recommended before treatment as the lungs 
are the most likely site of metastasis for STS 
when it occurs. • Contrast CT or MRI can 
be used to determine extent of disease and to 
optimize treatment planning (surgery or 
radiation). • Abdominal ultrasound may be 
indicated for diagnosis of intra ­abdominal 
STS and to allow assessment of liver, spleen, 
and abdominal lymph nodes.
• Fine­needle aspiration and cytology can 
rule out other differential diagnoses and may 
suggest a diagnosis but a nondiagnostic 
sample is possible as cells do not always 
exfoliate well. • Incisional biopsy and 
histopathology is essential to confirm 
diagnosis, determine grade of the tumor, and 
plan surgical approach. • Regional lymph 
node evaluation (cytology or histopathology) 
is indicated for assessment of enlarged 
regional lymph nodes and for high ­grade 
tumors to evaluate for regional metastasis.
Dogs
• Over 20 different histopathologic subtypes 
of STS exist; biologic behavior is similar 
regardless of subtype. • Histologic grading 
based on differentiation, number of mitotic 
figures per 10 high power fields and percentage 
necrosis: ◦ Grade I (low grade). ◦ Grade II 
(intermediate grade). ◦ Grade III (high grade) 
is the most biologically aggressive.
Cats
• Some similarities between histopathologic 
subtypes compared to dogs. Peripheral nerve 
sheath tumors are rare in cats. • Vaccine or 
injection site sarcomas have a more aggressive 
histologic appearance compared to other 
naturally occurring sarcomas.
  TREATMENT
A mass lesion with nondiagnostic and low 
cellularity cytology should be suspicious for a 
sarcoma. Postvaccination lumps in cats 
should be biopsied if they are growing larger 
within 1 month, are greater than 2 cm, or 
persist beyond 3 months after first appearing.
• Early, aggressive, en bloc  surgical excision is 
the treatment of choice. Conventional 
recommendations are 3 cm margins and 1 
fascial plane deep (2 fascial planes deep for 
feline injection site sarcoma [FISS]). Even with 
complete excision, FISS can recur (30% or 
greater). • Do not place a drain through 
normal adjacent tissue during surgery if 
margins are uncertain. • Microscopically,

Canine and Feline, Seventh Edition  1271
Scancer cells extend far beyond palpable tumor 
borders and recurrence is common if only 
macroscopic tumor is removed or peeled away 
from pseudocapsule. • Pseudocapsule 
composed of compressed cancer cells is 
common. • A second surgery (scar resection) 
can be performed prior to recurrence after 
incomplete excision to achieve more complete 
margins and decreased risk of recurrence. 
• After excision, tack mobile fascial layers in 
place and apply ink to surgical borders to 
thoroughly evaluate margins; submit the entire 
sample to a pathologist for surgical margin 
evaluation. Mark margins of greatest interest 
with suture or different color ink. • Toe or limb 
amputation may be necessary with large tumors 
that may be otherwise unresectable. • Rib 
resection or abdominal wall resection may be 
required for tumors of the trunk. • The first 
surgery usually provides the best opportunity 
for local tumor control. • Recurrent tumors 
will require different therapy rather than just 
repeating the same surgery (typically radiation 
therapy or a much larger surgery).
Dogs
Radiation therapy can be used to treat 
microscopic disease (postoperatively with 
incomplete histologic margins, finely 
fractionated) or for measurable/unresectable 
disease (often hypofractionated).
Cats
Given the high rate of recurrence with feline 
injection site sarcoma, fractionated radiation 
therapy should be considered regardless of 
quality of margins, though outcomes after 
complete excision followed by radiation 
therapy are superior to those following 
incomplete excision and radiation therapy.
Dogs
• Doxorubicin ­based chemotherapy can be 
used after excision of a high ­grade (grade III) 
tumor, though a significant benefit has not 
been reported (1 mg/kg for small dogs or 30 
mg/m2 for medium and large dogs, IV, 5 
doses q14–21 days). • Low­dosage (metronomic) cyclophosphamide chemo­
therapy 10–15 mg/m2 PO q48h in 
combination with piroxicam 0.3 mg/kg 
PO q24–48h may help delay local recurrence 
when the tumor is incompletely resected.
Cats
• Role of postoperative chemotherapy in cats 
with STS is unclear. Chemotherapy treatment 
may improve local disease control but has 
minimal effect on survival in cats following 
wide surgical excision or radiation therapy 
(doxorubicin 1 mg/kg IV q3 weeks for 5 
doses). • Toceranib has not been effective in 
treating FISS.
• Doxorubicin—cardiotoxic in dogs, avoid if 
underlying myocardial disease; nephrotoxic in 
cats, avoid if underlying renal disease; myelo  ­ 
suppressive in both species; severe vesicant, 
causes severe local tissue necrosis with 
extravasation (treat with dexrazoxane 
immediately). • Cyclophosphamide—can 
cause sterile hemorrhagic cystitis. Monitor for 
signs of hematuria and pollakuria; discontinue 
medication if this occurs. • Both drugs require 
adequate hepatobiliary function.
Analgesia if needed.
  FOLLOW-UP
Every 3 months for 1 year, then every 4–6 
months thereafter: • Physical examination—
local regrowth. • Thoracic radiographs—
N/A
• Surgical complications including infection or 
incisional dehiscence. • Chemotherapy toxicity 
(see Contraindications and Precautions).
• Strong prognostic factors—grade, 
especially mitotic index (recurrence, 
metastasis, survival time), size at surgery (>5  cm more likely to recur) and incomplete 
surgical margins (recurrence). • Low­grade 
STS of the distal extremities in dogs might 
have a low recurrence rate following surgical 
excision (<20%). • In dogs, cure is possible 
with low ­ and intermediate ­grade STS with 
wide surgical resection, or surgery and 
adjuvant radiation therapy with median 
survival times of over 3 years. • The 
prognosis is more guarded and variable with 
high­grade tumors (7–24 months). • Cats 
with FISS treated with surgery and radiation 
therapy have median survival times of 
2–3 years.
While receiving chemotherapy, dogs should 
SYNONYMS
Spindle cell tumor/sarcoma.
• FISS = feline injection site sarcoma.
www.vetcancertrials.org
Ehrhart N. Soft ­tissue sarcomas in dogs: a 
review. J Am Anim Hosp Assoc 2005, 
41:241–246.
Kuntz CA, Dernell WS, Powers BE, et al. 
Prognostic factors for surgical treatment of 
soft tissue sarcomas in dogs: 75 cases 
(1986–1996). J Am Vet Med Assoc 1997, 
211:1147–1151.
Muller N, Kessler M. Curative ­intent radical 
en bloc resection using a minimum of a 3 
cm margin in feline injection ­site sarcomas: 
a retrospective analysis of 131 cases. J Feline 
Med Surg 2018, 20:509–519.
acknowledge the prior contributions of Laura 
E. Selmic and Shawna L. Klahn.(continued)  Soft Tissue Sarcoma

1272  Blackwell’s Five-Minute Veterinary Consult  
SSpermatocele/Sperm Granuloma
  BASICS
OVERVIEW
• Spermatocele—a local, cystic distension of 
the efferent ductules or epididymis.
• Sperm granuloma—a chronic inflammatory 
reaction resulting from the immune response 
following sperm leakage from the efferent 
ductules or epididymal duct.
Intact male dogs and cats.
SIGNS
• Sperm granuloma—oligozoospermia or 
azoospermia if obstruction exists.
• Spermatocele—cystic mass adjacent to the 
testicle, with or without discomfort.
• T rauma to epididymal duct causing release 
of sperm antigens into the surrounding 
tissue.
• Epithelial hyperplasia of the epididymis as 
documented in dogs of increasing age.
• Congenital occlusion of epididymal duct.
• Complication of surgical vasectomy.
  DIAGNOSIS
• Azoospermia—testicular degeneration, 
hypoplasia, retrograde ejaculation, incomplete 
ejaculation.
• Scrotal discomfort—epididymitis; orchitis; 
scrotal dermatitis.
• CBC and biochemistry profile—usually 
normal.
• Urinalysis (cystocentesis) after ejaculation—
rule out retrograde ejaculation.
• Assay for serum canine follicle-stimulating 
hormone (FSH) concentration—elevated 
with degeneration and hypoplasia; normal in 
azoospermic dogs experiencing retrograde 
ejaculation or bilateral epididymal blockage. 
Currently commercially unavailable.
• Alkaline phosphatase concentration of 
seminal plasma—concentration <5,000 U/L 
consistent with bilateral epididymal blockage 
or incomplete ejaculation (see Infertility, 
Male—Dogs).
IMAGING
Ultrasonography—useful to differentiate 
from other testicular or scrotal conditions.DIAGNOSTIC PROCEDURES
Surgical testicular biopsy and excisional 
biopsy of affected epididymal tissue—allows 
visualization of epididymis, assess spermato-
genesis (diagnostic for testicular degenera-
tion); spermatoceles appear as yellow cysts 
within the epididymis.
Histologic examination of testicular 
biopsy—complete spermatogenesis in an 
azoospermic dog indicates blockage.
  TREATMENT
Azoospermia rarely resolves if due to bilateral 
epididymal blockage; microsurgical anasto-
mosis of the ductus deferens to the dilated 
epididymal tubule has been attempted.
None described in the literature to unblock 
the duct system.
  FOLLOW-UP
• Unilateral sperm granuloma resulting in 
oligozoospermia—case-dependent; could be 
good to guarded for fertility depending on 
total sperm number and accuracy of breeding 
management (see Breeding, Timing).
• Bilateral sperm granuloma resulting in 
azoospermia—poor prognosis for fertility.
SEE ALSO
Althouse GC, Evans LE, Hopkins SM. 
Episodic scrotal mutilation with concurrent 
bilateral sperm granuloma in a dog. J Am 
Vet Med Assoc 1993, 202:776–778.
James RW, Heywood R. Age-related variations 
in the testes and prostate of beagle dogs. 
Toxicology 1979, 12(3):273–279.Mayenco Aguirre AM, Garcia Fernandez P , 
Sanchez Muela M. Sperm granuloma in the 
dog: Complication of vasectomy. J Small 
Anim Pract 1996, 37:392–393.
Perez-Marin CC, Lopez R, Dominguez KM, 
Zafra R. Clinical and pathological findings 
in testis, epididymis, deferens duct and 
prostate following vasectomy in a dog. 
Reprod Domest Anim 2006, 41:169–174.

Canine and Feline, Seventh Edition  1273
SSpermatozoal Abnormalities
  BASICS
OVERVIEW
• Teratozoospermia—sperm abnormalities of 
≥40% in the ejaculate (i.e., low percentage of 
morphologically normal sperm).
• High percentage of sperm abnormalities 
may affect fertility.
• Some fertile cats inherently have ≥40% 
• Sperm abnormalities may also be classified 
as primary (those occurring during spermato-
genesis) or secondary (those occurring during 
epididymal storage and transport or from 
inappropriate semen handling).
• Dogs and cats of any age; older dogs and 
cats more likely to have age-related 
SIGNS
• Persistent infertility after appropriately 
timed mating to several reproductively proven 
bitches.
• Abnormalities identified during semen 
• Canine fucosidosis—rare lysosomal storage 
disorder ( α-l-fucosidase deficiency); acroso-
mal defects, proximal droplets, bent tails; 
autosomal recessive inheritance in English 
• Primary ciliary dyskinesia—ultrastructural 
abnormality of cilia causing absent or 
abnormal motility of ciliated cells; affected 
animals are infertile; probably autosomal 
recessive inheritance.
• Testicular hypoplasia.
Acquired
• Conditions disrupting normal testicular 
thermoregulation—trauma, hematocele, 
hydrocele, orchitis, epididymitis, fever, 
obesity (increased scrotal fat), high environ-
mental temperatures, exercise-induced heat 
exhaustion.
• Infections of the reproductive tract.
• Overuse.
• Testicular neoplasia.
• Testicular degeneration.
• Prolonged sexual abstinence.
• Drugs—anabolic steroids, androgens, 
estrogen, progestogens, corticosteroids, 
ketoconazole, amphotericin B, cimetidine, 
phytoestrogen, gonadotropin-releasing 
hormone antagonists, intratesticular 
injections of zinc arginine.  DIAGNOSIS
Excessive kinked or coiled tails may be 
iatrogenic, caused by morphology stain; 
reexamine the sample under phase contrast 
microscopy after dilution with formalin 
phosphate-buffered saline solution.
• Hormonal profile—concentrations of 
gonadotropin and steroid hormones should 
be determined to rule out endocrinopathies.
• Azoospermic ejaculates—alkaline phos-
phatase concentration should be >5,000 U/L 
in complete ejaculates.
• Rapid slide agglutination test (brucellosis)—  
used as a screening test, recommend recheck 
of dogs with positive slide test with agar gel 
immunodiffusion test or other listed methods 
(see Brucellosis).
IMAGING
Ultrasonography—to visualize abnormalities 
in testes or scrotum that may promote 
abnormal spermatogenesis.
• Semen morphology (bright-field micros-
copy)—eosin–nigrosin stain or modified 
Giemsa stain; a minimum of 100 (preferably 
200) sperm cells are counted under oil 
immersion (100× objective).
• Acrosome staining—acrosomal damage can 
be evaluated by Coomassie Brilliant blue 
staining or Spermac stain.
• Wet-mount semen morphology (phase 
contrast or differential interference contrast 
light microscopy)—samples diluted with 
formalin phosphate-buffered saline solution; 
verifies if presence of kinked or coiled tails on 
a stained slide is due to staining artifact.
• Biopsy—reveals spermatogenic capability of 
testicle; absence of spermatids or spermato-
cytes confirms impaired spermatogenesis.
• Inflammation—peritubular lymphocytic 
• Degenerative changes.
• Hypoplasia.
  TREATMENT
• Unilateral orchiectomy for unilateral 
testicular tumors or severe orchitis.
• Sexual rest for edema or hematocele 
associated with trauma.
• If inciting cause was transient and has 
resolved, semen collection may “improve” 
individual ejaculate quality by depleting 
affected sperm cells.• Adjust environment and avoid exercise/
competitive events that may induce heat stress 
in the 2 months leading up to when optimal 
semen quality is needed for breeding or 
processing.
• Exogenous hormones—anabolic steroids, 
estrogens, testosterone, progestagens.
• Ketoconazole, amphotericin B.
• Cimetidine.
  FOLLOW-UP
• In cases from reversible causes, a complete 
improvement in sperm morphology will not 
occur before 70 days (approximate length of a 
complete spermatogenic cycle).
• After an underlying cause is identified and 
treated, a semen evaluation performed at 70 
days will provide an indication as to long- 
term expectations for semen quality.
• Climate-controlled environment for 
animals not adapted to high environmental 
temperatures.
• Avoid heat exhaustion during exercise or 
grooming.
Kolster KA. Evaluation of canine sperm and 
North Am Small Anim Pract 2018, 
48(4):533–545.

1274  Blackwell’s Five-Minute Veterinary Consult  
SSpider Venom Toxicosis—Black Widow
  BASICS
OVERVIEW
• Black widow spider ( Latrodectus  spp.)—
four species indigenous to the United States 
(L. mactans , L. geometricus , L. hesperus , L. 
variolus ); females toxic; 2–2.5 cm in length; 
shiny black; red or orange hourglass mark on 
the ventral abdomen; immature female brown 
with red to orange stripes that change into 
the hourglass shape as she darkens to black 
and ages.
• Bites—15% may be dry (no venom 
injected).
• Range—genus found in every state except 
Alaska; often found around buildings and 
human habitation.
• Venom—contains α-latrotoxin, a potent 
presynaptic neurotoxin; opens cation-selective 
channels at the nerve terminal; causes massive 
release of acetylcholine and norepinephrine, 
which causes sustained muscular spasms. T wo 
classes of receptors for α-latrotoxin: the 
neurexins, which are brain-specific cell 
adhesion molecules binding in a Ca2+-
dependent manner, and latrophilins (and 
CIRLs), which are not brain specific, 
expressed in many tissues, and bind 
α-latrotoxin independent of Ca2+.
SIGNS
• Usually sudden onset.
• May be delayed several days with mild 
Dogs
• Severe pain is the primary clinical sign.
• Progressive muscle fasciculations.
• Cramping of large muscle masses.
• Abdominal rigidity without tenderness.
• Marked restlessness, writhing, and 
contorted spasms.
• Hypertension and tachycardia anticipated.
• May note bronchorrhea, hypersalivation, 
hyperesthesia, lymph node tenderness, 
regional numbness, facial swelling and spasm 
(referred to as Latrodectus  facies).
• Rhabdomyolysis possible.
Cats
• Early, marked paralysis.
• Severe pain—manifested by howling and 
loud vocalizations.
• Excessive salivation and restlessness.
• Vomiting—not unusual to vomit up the 
spider.
• Muscle tremors and cramping.
• Ataxia and inability to stand—becomes 
adynamic and atonic.• Respiratory collapse.
• Death without antivenin.
• Very young or old age—increased risk.
• Systemic hypertension—increased risk.
  DIAGNOSIS
• Acute abdomen.
• High creatine kinase—with severe muscle 
spasms.
• Albuminuria.
Normal hemoccult test.
N/A
  TREATMENT
• Inpatient—supportive care.
• Monitor respiratory status.
• Antivenin (Lyovac [ Latrodectus ], equine 
origin—Merck) 1 vial mixed with 100 mL 
crystalloid solution IV given slowly with 
monitoring of the inner ear pinna for 
evidence of hyperemia (indicator of allergic 
response); this dose is usually sufficient for 
response within 30 minutes; with proper use, 
reactions are rare. Variable availability. If 
allergic reaction occurs—stop antivenin; 
administer diphenhydramine; after 5–10 
minutes, restart antivenin at a slower rate.
• New antivenin (Aracmyn; Instituto 
Bioclon, Mexico—managed by Rare Disease 
Therapeutics in the United States) has 
completed human phase III clinical trials but 
not yet approved for human use. It is an 
equine origin Fab2 product and should be 
much less likely to trigger an allergic response.
• There are multiple latrodectus antivenoms 
worldwide which have crossreactivity with 
black widow spider venom, including 
Australian red back spider antivenom 
(Commonwealth Serum Laboratories), South 
Africa (SAFR) brown widow antivenom, and 
the Yugoslavian widow spider antivenom.
• Studies suggest benzodiazepines are more 
effective than muscle relaxants for treatment 
of muscle pain related to black widow spider 
envenomation.• Muscle spasms and severe pain are 
controlled by careful IV administration of 
narcotics or benzodiazepines at lowest 
effective dosage to avoid respiratory depres-
sion; methocarbamol relieves muscle spasms 
but has no effect on hypertension or 
• Intractable hypertension—sodium 
nitroprusside.
IV fluids with hypertension.
  FOLLOW-UP
• Weekly monitoring of the wound site until 
healed.
• Prognosis—uncertain for days; cats, usually 
fatal without antivenin.
• Weakness, fatigue, and insomnia—may 
persist for months.
Peterson ME. Spider envenomation: black 
widow. In: Peterson ME, Talcott PA, eds., 
Small Animal Toxicology, 3rd ed. St. Louis, 
MO: Saunders, 2013, pp. 817–821.

Canine and Feline, Seventh Edition  1275
SSpider Venom Toxicosis—Brown Recluse
  BASICS
OVERVIEW
• Brown recluse family— Loxosceles  spp. (11 
species indigenous to United States); 8–15 
mm in body size; legs 2–3 cm long; violin-
shaped pattern on cephalothorax with the 
neck of the fiddle extending caudally; 6 eyes 
(3 paired diads) as opposed to other spider 
species with 8 eyes; active at night.
• Distribution—found throughout the 
Midwest from the Gulf Coast of the United 
States and up the Mississippi River valley to 
southern Iowa. Some species are found in 
eastern southern California, western Arizona, 
and southern New Mexico.
• 60% of “brown recluse” spider bites in 
humans are misdiagnosed as they occur in 
areas with no endemic spider populations. See 
extensive Differential Diagnosis.
• Bites usually occur when spider becomes 
trapped in bedding; induce, necrotic 
arachnidism, an indolent dermatonecrotic 
lesion mediated by the venom enzyme 
sphingomyelinase D, direct hemolysis of 
erythrocytes, platelet aggregation, renal 
failure, coagulopathy, and death.
• Currently no consensus on treatment and 
multiple therapies have been used, including 
antihistamines, corticosteroids, dapsone, 
hyperbaric oxygen, surgical excision, and 
antivenom.
• Antivenom currently unavailable in United 
States (available only in Argentina, Brazil, and 
Mexico).
SIGNS
• Clinical signs are not completely defined in 
canine and feline envenomations.
• In humans:
◦ Local pain and stinging (may last 6–8 
hours); followed by pruritus and soreness.
◦ Classic target lesion—ischemic area with a 
dark central eschar on an uneven erythematous 
background; after 2–5 weeks, central eschar 
may slough, leaving a deep, nonhealing ulcer 
that usually spares muscle tissue.
◦ Not all skin lesions develop necrosis.
◦ Less common—hemolytic anemia with 
hemoglobinuria in the first 24 hours; 
secondary renal complications.
◦ Skin lesion severity and hemolysis are not 
linked.
◦ Other possible systemic manifestations 
within the first 2–3 days after 
envenomation: fever; chills; rash; weakness; 
leukocytosis; nausea; arthralgia.
◦ Envenomations to fatty areas develop 
more significant lesions; those occurring in 
loose tissue more likely to be edematous.CAUSES & RISK FACTORS
Brown recluse spider bite (genus Loxosceles ).
  DIAGNOSIS
• Brown recluse spider bite is frequently 
misdiagnosed in regions of the country that do 
not have endemic populations of the spider.
• Epidemiologic history of bite including site 
of lesion, progression timeline of signs, and 
visualization of small puncta assist with 
• Bacterial or mycobacterial infection; 
methicillin-resistant Staphylococcus aureus  by a 
large margin in humans.
• Decubitus ulcer.
• Third-degree burn.
• Necrotizing vasculitis.
• Red blood cell parasitism.
• Vascular occlusive/venous disease.
• Anemia.
• Hemoglobinuria.
• BUN and creatinine.
• Coagulation profile—may reveal prolonged 
clotting times.
N/A
  TREATMENT
• Routine wound care—may need aggressive 
• Supportive care—may include fluid therapy; 
secondary infections are infrequent; blood 
transfusion (rarely).
• Mild, local envenomation—usually responds 
to cool compresses as sphingomyelinase D 
activity is temperature dependent.
• Necrotic lesions—may need debridement 
after erythema has subsided.
• Severe envenomation—may require skin 
grafting after the lesion reaches full maturity.
• Tetracycline can be applied topically as a 
matrix metalloproteinase inhibitor.• Hyperbaric oxygen—some evidence 
indicates that hyperbaric oxygen treatment 
may be beneficial for reducing size of the 
skin lesion.
• Dapsone—mixed results in various studies; 
1 mg/kg q8h orally for 10 days; for 
dermatonecrotic lesions; leukocyte inhibitor; 
proposed to minimize inflammatory 
component of envenomation; repeat if 
needed. Efficacy against brown recluse 
envenomation has not been studied in the 
dog and cat.
• Do not use heat—exacerbates condition.
• Dapsone—may cause hypersensitivity and 
methemoglobinemia in patients with 
glucose-6-phosphate dehydrogenase 
• Early surgical excision may cause larger 
defect than supportive care alone.
• Antihistamines, colchicine, anticoagulants, 
topical nitroglycerine, high doses of vitamin 
C, electric shock, and steroids have been 
proposed for treatments, but subsequently 
have been demonstrated to be ineffective.
  FOLLOW-UP
Monitor wound site weekly until healed.
Peterson ME. Spider envenomation: brown 
recluse. In: Peterson ME, Talcott PA, eds., 
MO: Saunders, 2013, pp. 823–826.
Swanson DL, Vetter RS. Bites of brown 
recluse spiders and suspected necrotic 
arachnidism. N Engl J Med 2005, 
352:700–707.

1276  Blackwell’s Five-Minute Veterinary Consult  
SSpinal Dysraphism
  BASICS
OVERVIEW
• Abnormal development of the embryonic 
spinal cord along the dorsal plane leading to a 
variety of structural anomalies (e.g., spina 
bifida, hydromyelia, duplicated or absent 
central canal, syringomyelia, aberrations in 
the dorsal median septum and ventral medial 
fissure, tethered cord).
• Thoracic and lumbar spinal segments most 
• ‘Dysraphism’ suggests an abnormality in 
closure of the neural tube; the term 
‘myelodysplasia’ (not to be confused with 
myelodysplastic syndrome) may be preferable 
when discussing anomalies with alternate 
pathogenesis.
• Reported in Rhodesian ridgeback, 
Weimaraner, English bulldog, pug, boxer, 
Victorian bulldog, golden retriever, Rottweiler, 
shih tzu, boerboel, chow chow, Siberian 
husky, English springer spaniel, Yorkshire 
terrier, Pyrenees mountain dog, Chinese 
crested dog, Swedish vallhund, and English 
cocker spaniel, Samoyed, Dalmatian, English 
setter; Manx cat, Burmese cat.
• Hereditary in the Weimaraner.
• Manx cat and brachycephalic breeds 
overrepresented, especially screw-tailed 
• Signs apparent by 3–6 weeks of age and 
become more obvious as animal matures. In 
mild cases, patient may not be presented for 
evaluation until several months of age.
• Adult cavalier King Charles spaniels with 
syringomyelia resulting from occipital bone 
malformation (Chiari-like malformation; 
caudal occipital malformation syndrome 
[COMS]).
• Described in an adult Pomeranian with 
cervical syringomyelia and hydrocephalus.
• Described in an adult fox terrier with 
progressive paresis in the left pelvic limb, a 
1-year-old English cocker spaniel with a 
9 months history of progressive paresis in 
the right pelvic limb.
SIGNS
Vary in severity. Normal neurologic examination 
does not rule out spinal dysraphism.
Dogs
• Associated physical exam findings include 
indentation of the epaxial muscles, abnormal 
hair streams in the dorsal cervical area (a 
desired trait in the Rhodesian ridgeback), kinking of the undocked tail, scoliosis, and 
koilosternia (depression of the sternum).
• In the Weimaraner, gait is characterized by 
simultaneous flexion and extension of pelvic 
limbs (bunny hopping). Proprioceptive 
deficits, base wide stance, and crouched pelvic 
limb posture are also often present.
• In animals with syringomyelia (e.g., cavalier 
King Charles spaniel with COMS), any 
combination of neck or head pain, progressive 
forelimb weakness, paraparesis, imbalance, 
paroxysmal involuntary flank or neck 
scratching may be present.
Cats
In affected Manx cats, pelvic limb paresis or 
paralysis, urinary and fecal retention, 
abnormal or absent caudal vertebrae, and 
structural abnormalities in the sacrum may be 
present.
• Missense mutation in the NKX2-8  gene in 
the Weimaraner. Homozygous condition 
lethal; heterozygotes clinically affected.
• Autosomal dominant trait controlling 
number and structure of caudal vertebrae in 
the Manx cat. Prevalence increased by 
breeding for absence of tail.
• In utero  spinal cord damage caused by 
infection, trauma, vascular compromise, 
drugs (antifungals, chemotherapeutics).
• Idiopathic in isolated patients.
• Syringomyelia may be acquired as result of 
infection, trauma, or neoplasia.
  DIAGNOSIS
Intervertebral disc disease, myelitis, arachnoid 
cysts, and neoplasia must be differentiated 
from progressive causes of syringomyelia.
IMAGING
• Spinal radiographs may show concurrent 
vertebral column anomalies and spinal cord 
compression in some patients.
• In patients with COMS, defects in the 
occipital bone may be appreciated on skull 
• MRI is necessary for definitive diagnosis of 
syringomyelia. Imaging shows attenuation of 
fourth ventricle, overcrowding of brainstem 
in caudal fossa, and cerebellar vermal hernia  - 
tion (COMS, Chiari-like malformation). 
Hydrocephalus may also be evident.
• One report of tethered cord in an English 
cocker spaniel in which conus medullaris was 
visibly caudodorsally displaced.
• CT reveals hydrocephalus, if present, with 
COMS.• Without sophisticated imaging techniques, 
an antemortem diagnosis may be impossible 
except in Weimaraner and Manx cat.
  TREATMENT
• Mildly affected animals may be acceptable 
pets.
• Severely affected, nonsurgical animals may 
benefit from a canine cart; consider euthanasia.
• Surgical options include foramen magnum 
remodeling (with occipital malformation) or 
ventriculoperitoneal shunt placement; 
laminectomy, ± syringo-subarachnoid 
shunting. These procedures may reduce pain 
or lead to improvement in neurologic signs. 
However, sensory disturbances such as 
scratching infrequently resolve, and 
• Antibiotics—for urinary tract infection. 
T reat based on culture and sensitivity of 
urine.
• Corticosteroids—to improve signs in 
COMS by reducing CSF production and 
edema formation. Prednisone 0.25–0.5 mg/
kg q12h or dexamethasone 0.025–0.05 mg/
kg PO q12h; taper to alternate-day 
prednisone or twice-weekly dexamethasone.
• Carbonic anhydrase inhibitors—may 
alleviate signs in COMS by decreasing CSF 
production and allow for a reduction of 
steroid dosage. Acetazolamide 3.5–7.5 mg/kg 
q8–12h, methazolamide 5 mg/kg q8–12h, or 
furosemide 5 mg/kg PO, IM, SC q12h.
• Omeprazole—decreases CSF production 
and may alleviate signs in COMS and allow 
for a reduction of steroid dosage. Clinical 
data on use and effectiveness currently 
lacking; 0.5–1 mg/kg PO q24h.
• Gabapentin—recommended for 
management of neuropathic pain; 10 mg/kg 
q8–12h or pregabalin (Lyrica) 4 mg/kg 
PO q12h.
(NSAIDs)—may help manage neuropathic 
pain. Meloxicam (Metacam) 0.2 mg/kg once 
then 0.1 mg/kg q24h in dogs; carprofen 
(Rimadyl) 2.2 mg/kg PO q12h or 4.4 mg/kg 
PO q24h in dogs.
• Avoid prolonged administration of NSAIDs, 
simultaneous use of of NSAIDs and 
acetaminophen, simultaneous use of NSAIDs 
and steroids, use of NSAIDs in patients with 
gastrointestinal or renal disease. Doing so

Canine and Feline, Seventh Edition  1277
Sdecreases risk of gastrointestinal ulceration 
and renal pathology.
• Do not use NSAIDs in cats.
  FOLLOW-UP
• Disorders of micturition predispose patients 
to secondary urinary tract infection.
• Avoid decubitus ulcers and urine and fecal 
scalds by properly caring for recumbent 
patients.
• Discourage breeding for absence of tail in 
Manx cats.• Do not breed Weimaraners that have 
produced affected puppies (codominant 
inheritance).
Congenital vertebral arch (e.g., spina bifida) 
and vertebral body–disc malformation (e.g., 
hemivertebra and block vertebra). These 
conditions alone often do not cause clinical signs.
syndrome.
• CSF = cerebrospinal fluid.• CT= computed tomography
• MRI = magnetic resonance imaging
drug.
SEE ALSO
Syringomyelia and Chiari-Like Malformation
Westworth DR, Sturges BK. Congenital 
spinal malformations in small animals. Vet 
40(5):951–981.
Authors  Richard J. Joseph and Anne E. Buglione(continued)  Spinal Dysraphism

1278  Blackwell’s Five-Minute Veterinary Consult  
SSplenic Torsion
  BASICS
OVERVIEW
• May occur as a separate entity or in 
association with gastric dilatation and 
volvulus (GDV) syndrome.
• Acute or chronic.
• Pathophysiology—unknown.
immune and cardiovascular.
• Isolated splenic torsion uncommon.
• More common in large-breed, deep-chested 
dogs, such as the German shepherd dog and Great 
Dane. English bulldogs are also predisposed.
SIGNS
• Acute—cardiovascular collapse and 
• Chronic—intermittent anorexia, vomiting, 
weight loss, and possibly hemoglobinuria.
• Pale mucous membranes, tachycardia, weak 
femoral pulses, other signs of hypoperfusion.
• Palpable abdominal mass (spleen).
• Irregular heart rate or dropped pulses if 
arrhythmias present.
• Large-breed and deep-chested dogs.
• Prior stretching of gastrosplenic, phrenico -
splenic, and splenocolic ligaments (e.g., prior 
GDV).
• Historical gastric dilatation.
• Excessive exercise, rolling, and retching may 
• Nervousness and anxiety have been 
associated with an increased risk of GDV but 
not of isolated splenic torsion.
  DIAGNOSIS
• Other splenic disease (e.g., neoplasia, 
thrombosis, immune-mediated disease).
• Acute gastrointestinal disease with 
abdominal pain (acute abdomen).
• Anemia.
• Elevated liver enzyme activities.
• Pigmenturia/hemoglobinuria.
Coagulation testing—prolongation of 
activated partial thromboplastin time (aPTT) or both prothrombin time (PT) 
and aPTT, with thrombocytopenia may 
indicate disseminated intravascular 
IMAGING
• Cranial or midabdominal mass may 
be seen.
• Spleen may be abnormally located.
• Splenic congestion/lack of blood flow to 
spleen.
• Dilated splenic veins.
• Splenic infarction.
Electrocardiogram (ECG)—may show 
Splenic congestion and infarction.
  TREATMENT
• Surgical emergency.
• After adequate cardiovascular stabilization, 
a splenectomy should be performed without  
untwisting the splenic pedicle.
• A permanent gastropexy should also be 
performed because of the association with 
GDV syndrome.
• A representative splenic specimen 
should be submitted for histopathologic 
• IV fluid support and cardiovascular 
monitoring are indicated after splenectomy.
• No specific drugs required.
• Postoperative pain relief advised.
• Plasma transfusion may be considered if 
DIC or coagulopathy are present.
• Antiarrhythmic drugs (e.g., lidocaine) may 
be indicated in the perioperative period.
None
  FOLLOW-UP
Surgical correction considered curative. 
Prognosis is good; mortality has been 
associated with preexisting septic peritonitis, 
hemorrhage or postoperative development of 
respiratory distress.  MISCELLANEOUS
SEE ALSO
time.
DeGroot W, Giuffrida MA, Rubin J et al. 
Primary splenic torsion in dogs: 102 cases 
(1992–2014). J Am Vet Med Assoc 2016, 
248(6):661–668.

Canine and Feline, Seventh Edition  1279
SSplenomegaly
  BASICS
Enlargement of the spleen; characterized as 
either diffuse, focal, or nodular.
• Splenic functions—removal of senescent and 
abnormal erythrocytes; filtration and phagocytosis 
of antigenic particles such as microorganisms, 
degraded cellular material, macromolecules; 
production of lymphocytes and plasma cells; 
antibody production, reservoir for erythrocytes 
and platelets; iron metabolism and storage, 
hematopoiesis, as required. • Many disorders 
affect function of spleen.
Diffuse Splenomegaly
Four General Pathologic Mechanisms
• Inflammation (splenitis)—associated with 
infectious agents; classified according to cell type 
(e.g., suppurative, necrotizing, eosinophilic, 
lymphoplasmacytic, and granulomatous-
pyogranulomatous). • Lymphoreticular 
hyperplasia—increased proliferation of 
mononuclear phagocytes and lymphoid 
elements (in response to antigens); accelerated 
erythrocyte destruction. • Congestion—
associated with impaired venous drainage. 
• Infiltration—involves cellular invasion of the 
spleen or deposition of abnormal substances.
Focal or Nodular lesions
Associated with neoplastic (benign or 
malignant) or non-neoplastic disorders 
(infection, hyperplasia/regeneration, or 
inflammation).
Disorders of the spleen may also be associated 
with changes in the liver and lymph nodes.
• Dog and cat; certain conditions maybe more 
prevalent in specific breeds or sizes of dog. 
• Splenic torsion—overrepresented in large, 
deep-chested breeds (e.g., German shepherd 
dog, Great Dane). • Hemangiosarcoma—
middle-aged dogs; large breeds; predilection in 
German shepherd dog, golden retriever, 
Labrador retriever, and boxer. • Prominent 
spleen—may be normal in certain breeds 
(German shepherd dog).
SIGNS
• Splenic enlargement—often nonspecific. 
• Frequently reflects an underlying disorder 
rather than primary disease of the spleen.
• Vomiting, diarrhea, anorexia—can be seen 
with infiltrative diseases such as lymphoma, 
mast cell tumor, feline infectious peritonitis 
(FIP), lymphoplasmacytic enteritis (cats). 
• Lethargy, anorexia, vomiting, vague 
abdominal pain (in acute cases pain can be 
severe), mild to moderate abdominal 
distention in deep-chested large to giant-breed dogs (Great Dane, German shepherd dog 
overrepresented)—associated with splenic 
torsion (with or without concurrent gastric 
dilatation and volvulus [GDV]). • Weakness, 
lethargy, collapse (can be episodic), abdominal 
distention—can indicate a hemoabdomen 
secondary to bleeding/ruptured splenic tumor 
(hemangiosarcoma most common) or benign 
conditions such as a hematoma.
• Prominent spleen on abdominal palpation 
or cranial/mid-abdominal mass; nonpalpable 
spleen does not preclude splenomegaly. 
• Dogs—smooth or irregular surface. 
• Cats—usually diffuse, uniform enlargement. 
• Pallor, poor capillary refill time, poor 
peripheral pulses and tachycardia if splenic 
hemorrhage or splenic torsion. • Abdominal 
distention if massive splenomegaly or splenic 
rupture (effusion). • Petechia and ecchymosis 
if coagulopathy secondary to primary splenic 
disorder or underlying disease. • Concurrent 
hepatomegaly, thickened intestines, and/or 
mesenteric lymphadenopathy imply 
infiltrative (neoplastic) or inflammatory 
(immune-mediated or infectious) disease. 
• Peripheral lymphadenomegaly—suggests 
lymphoma/leukemia or histiocytic sarcoma. 
• Cardiac arrhythmias—can be seen with 
primary cardiac disease affecting the spleen 
(congestion) or can be associated with primary 
splenic disorders.
CAUSES
Dogs
Inflammation (Splenitis)
• Inflammatory cell type can help prioritize 
differentials. • Suppurative (neutrophilic)— 
bacterial infections associated with penetrating 
abdominal wound; migrating foreign body; 
endocarditis; sepsis; infectious complication of 
splenic torsion. • Necrotizing—most commonly 
associated with anaerobic infections (often 
secondary to splenic torsion), or neoplasia. 
• Eosinophilic—eosinophilic gastroenteritis, 
hypereosinophilic syndrome. 
• Lymphoplasmacytic—subacute or chronic 
infectious disorders; pyometra; coexistent 
inflammatory bowel disease. 
• Granulomatous—fungal or protozoal disease 
most common. • Pyogranulomatous—bacterial 
or fungal infections most common cause.
Hyperplasia
• Infection—chronic bacteremia (bacterial 
endocarditis; discospondylitis; Brucella ). 
• Immune-mediated disease—any; hemolytic 
anemia or thrombocytopenia, systemic lupus 
erythematosus (SLE).
Congestion
T ranquilizers; barbiturates; portal hypertension; 
right-sided heart failure; splenic torsion.
• Neoplasia—lymphoma; acute and chronic 
leukemia; (hemophagocytic) histiocytic sarcoma; 
multiple myeloma; systemic mastocytosis; 
hemangiosarcoma, other sarcoma; metastasis. • Extramedullary hematopoiesis (EMH)—
immune-mediated hemolytic anemia or 
thrombocytopenia; chronic anemia; infectious 
disease; malignancy; SLE. • Amyloidosis – part 
of systemic amyloidosis.
Cats
• Suppurative—penetrating wound or 
migrating foreign body; septicemia; 
salmonellosis. • Necrotizing—salmonellosis. 
• Eosinophilic—hypereosinophilic syndrome. 
• Lymphoplasmacytic—lymphoplasmacytic 
enteritis; hemotropic mycoplasmas; pyometra. 
• Granulomatous—histoplasmosis; 
mycobacteriosis. • Pyogranulomatous—FIP , 
Mycobacterium .
• Infection—hemotropic mycoplasmosis. 
• Immune-mediated—any; hemolytic 
disorders, SLE.
Portal hypertension, congestive heart failure.
• Neoplasia—mast cell tumor, lymphoma; 
lympho- or myeloproliferative diseases; 
multiple myeloma; histiocytic sarcoma (rare); 
hemangiosarcoma (rare). • Non-neoplastic—
amyloidosis, EMH.
• Cats—feline leukemia virus (FeLV), FIP . 
• Dogs—breed/age.
  DIAGNOSIS
Other cranial organomegaly or masses.
Dogs
• Regenerative anemia secondary to splenic 
bleeding or hemolytic disease. • Nucleated red 
blood cells (RBCs)—may accompany EMH, 
indicates splenic dysfunction. • Spherocytes—
hemolysis, microangiopathic shearing. 
• Schizocytes (aka schistocytes) – disseminated 
intravascular coagulation (DIC), hemangio -
sarcoma. • Acanthocytes- hemangiosarcoma. 
• Leukocytosis with a left shift—may indicate 
infectious or inflammatory conditions, marked 
regenerative response, or EMH. 
• Thrombocytopenia—from increased 
consumption (DIC or bleeding) secondary to 
hemangiosarcoma or other neoplasia, increased 
destruction (immune-mediated), sequestration, 
or decreased production in the bone marrow. 
• Hypercalcemia may be associated with 
neoplasia, especially lymphoma. 
• Hyperglobulinemia may be associated with 
neoplasia, Ehrlichia  infections. 
• Hemoglobinemia and hyperbilirubinemia— 
associated with hemolysis and may occur with 
microangiopathic anemia, splenic torsion, 
hemangiosarcoma, and immune-mediated 
anemia.

1280  Blackwell’s Five-Minute Veterinary Consult  
SCats
• Direct RBC examination for hemoparasites. 
• Regenerative anemia and splenomegaly—
may indicate hemotropic mycoplasmosis. 
• Macrocytosis and nonregenerative anemia—
suggests retroviral infection or myeloproli -
ferative disease. • Eosinophilia—suggests 
hypereosinophilic syndrome, systemic 
mastocytosis, or lymphoma. • Circulating blast 
cells—suggest lympho- or myeloproliferative 
disorder. • Nucleated RBCs—may accompany 
EMH and splenic dysfunction. • Thrombo -
cytopenia—from increased consumption 
(DIC), increased destruction (immune-  
mediated), sequestration, or decreased 
production in the bone marrow.
• FeLV and feline immunodeficiency virus 
testing. • Coagulation panel—DIC commonly 
seen with hemangiosarcoma (includes prolonged 
clotting times, hypofibrinogenemia, and 
increased fibrin degradation products [FDPs]); 
D-dimers not specific for clinical application 
in differential diagnoses).
IMAGING
• Confirms or detects splenomegaly. • Mass 
effect may appear in the (left) midcranial 
abdomen. • May provide evidence of an 
underlying cause—concurrent hepatomegaly 
may indicate infiltrative disease or right-sided 
heart disease; splenic torsion secondary to GDV. 
• Effusion—may indicate hemorrhage from 
splenic rupture (hemangiosarcoma, hematoma) 
or portal hypertension influencing splenic 
perfusion. • Visualization of the splenic tail along 
the ventral body wall on lateral radiographs of 
cats supports the diagnosis of splenomegaly.
• Three views (right and left lateral and dorsal–
ventral views)—screen for metastasis and 
underlying disease in thoracic cavity and 
effusion. • Evaluate sternal lymph nodes—these 
drain the abdominal cavity, reflecting disorders 
causing lymphadenomegaly. Evaluate for signs 
of congestive heart failure (size of the cardiac 
silhouette and pulmonary veins and evidence of 
pulmonary edema or pleural effusion).
• Distinguishes between diffuse and focal/
nodular parenchymal patterns. • Diffuse 
enlargement with normal parenchyma—may 
occur with congestion or cellular infiltration. 
• In cats splenic masses greater than 1 cm 
suggestive of malignancy. • Hypoechogenicity 
may occur with splenic torsion, splenic vein 
thrombosis, hematopoietic neoplasia or 
infectious agents. • Complex, mixed 
echogenic mass—common with hemangio -
sarcoma or hematoma. • Can identify 
concurrent abdominal diseases—liver, 
kidneys, intestines, and lymph nodes. 
• Cannot differentiate between benign and 
malignant splenic disorders. • Doppler color flow interrogation of splenic vasculature may 
detect splenic vein thrombi or splenic torsion.
Evaluate for cardiac dysfunction or cardiac 
tumors causing splenic congestion (based on 
other physical exam/imaging findings).
• Assess coagulation status before any 
aspiration. Procedure—patient in right lateral 
or dorsal recumbency; using ultrasound 
guidance, use a 22- or smaller gauge, 2.5–3.75 
cm (1–1.5 in.) length needle depending on the 
size of the patient. • Non-aspiration method 
(needle-only method) results in higher yield of 
nucleated cells relative to the amount of blood 
than aspiration method. • Specimens—
evaluate cytologically for infectious agents 
(often found in macrophages); identify 
predominant inflammatory or infiltrative cell 
type. • Neoplastic infiltrates—classified as 
epithelial, mesenchymal, or round cell. 
• Aspiration of cavitated masses may cause 
rupture and is not recommended.
Bone Marrow Aspiration
• Indicated with cytopenias before splenectomy 
(spleen may be supporting hematopoiesis). 
• May yield infectious disorder (e.g., 
ehrlichiosis, mycosis, toxoplasmosis, 
leishmaniosis) or hematopoietic neoplasia.
  TREATMENT
• Depends on underlying cause; 
supportive nursing care as needed. 
• Important to determine if splenomegaly 
is appropriate for systemic conditions. 
• T reatment and prognosis after 
splenectomy—based on histopathologic 
features: submit the entire spleen for 
histopathologic evaluation (hemangio -
sarcoma may be missed in some tumors 
owing to regional necrosis with diagnosis 
rendered of hematoma).
Splenectomy
• With anemia or leukopenia—rule out bone 
marrow aplasia/hypoplasia before surgery; 
spleen may be the source of hematopoiesis. 
• Indicated for splenic torsion, splenic 
rupture, isolated splenic masses considered 
likely to be neoplastic, and mast cell 
infiltration (cats only). • Exploratory 
laparotomy—permits direct evaluation of all 
Depend on underlying disease.  FOLLOW-UP
Ventricular arrhythmias (dogs)—associated 
with splenic mass lesions or torsion; may 
occur before, during, and up to 3 days post 
splenectomy; evaluate (auscultation and 
electrocardiogram) surgical candidates 
before anesthesia; continuous cardiac 
monitoring during surgery and post  - 
operatively.
• Asplenic patient—increased risk of 
infection and red cell parasitism. 
• Postoperative sepsis—uncommon 
complication. • Antibiotics—indicated in 
asplenic patients receiving 
immunosuppressive therapy, if any sign of 
infection apparent.
Neoplastic causes more likely in geriatric 
animals.
A variety of infectious diseases may involve 
the spleen.
SEE ALSO
coagulation. • GDV = gastric dilatation and 
volvulus. • EMH = extramedullary 
hematopoiesis. • FDP = fibrin degradation 
product. • FeLV = feline leukemia virus. 
red blood cell. • SLE = systemic lupus 
Cleveland MJ, Casale S. Incidence of 
malignancy and outcome for dogs 
undergoing splenectomy for incidentally 
detected nonruptured splenic nodules or 
masses: 105 cases (2009 – 2013). J Am Vet 
Med Assoc 2016, 248:1267–1273.
Ferri F , Zini E, Auriemma E, et al. 
Splenitis in 33 dogs. Vet Pathol 2017, 
54:147–154.
Spangler WL, Culbertson MR. Prevalence 
and type of splenic diseases in cats: 455 
cases (1985–1991). J Am Vet Med Assoc 
1992, 201:773–776.
Spangler WL, Kass PH. Pathologic factors 
affecting postsplenectomy survival in dogs. 
J Vet Intern Med 1997, 11:166–171.
Author  Cheryl E. Balkman
Consulting Editor  Kate HolanSplenomegaly  (continued)

Canine and Feline, Seventh Edition  1281
SSpondylosis Deformans
  BASICS
OVERVIEW
• Degenerative, noninflammatory condition 
of the vertebral column that occurs in 
response to intervertebral disc degeneration.
• Often an incidental finding, rarely clinically 
• Characterized by the production of osteophytes 
along the ventral, lateral, and dorsolateral aspects 
of the vertebral endplates. Radiographically, 
appears as smooth, ventral bridging bone.
• Most common location in dogs is the 
thoracolumbar spine in the area of the 
anticlinal vertebra and the upper lumbar 
vertebrae; in cats, the thoracic vertebrae.
• Females > males.
• Dogs—commonly seen in large breeds, 
especially German shepherd dog; also boxer, 
Airedale terrier, and cocker spaniel.
• Occurrence increases with age. Present in 
50% of dogs by 6 years and 75% by 9 years. 
May be radiographically evident in young 
dogs with an inherited predisposition.
• Boxers—positive correlation between 
spondylosis deformans and hip dysplasia. Both 
heritable traits are detectable in predisposed 
animals by radiographic examination at 1 year.
• Cats—present in 68% of asymptomatic cats.
SIGNS
• Patients are typically asymptomatic; lesions 
are of minor if any clinical importance.
• Pain may follow fracture of bony spurs or 
bridges.
• Stiffness.
• Restricted motion.
• Spinal pain.
Neurologic deficits are uncommon. If 
present, referable to compression of the spinal 
cord or nerve root.
• Repeated microtrauma.
• Major trauma.
• Inherited predisposition.
  DIAGNOSIS
• Discospondylitis—differentiated by 
radiographic evidence of endplate lysis.
• Spinal osteoarthritis—degeneration of 
articular facet joints.• Neoplasia—may have irregular, ventral, 
nonbridging bone.
Normal
Spinal radiography initially shows osteophytes 
as triangular projections several millimeters 
from the edge of the vertebral body. With 
progression, osteophytes appear to bridge the 
intervertebral space. T rue ankylosis is rare.
In uncommon presentations, MRI, CT, or 
CT myelography can be used to demonstrate 
an atypical dorsal osteophyte compressing the 
spinal cord or nerve roots or encroaching on 
critical soft tissue structures.
  TREATMENT
• Typically not needed. Inform client that the 
condition is usually an asymptomatic, 
incidental finding, and is likely not respons­
ible for any clinical signs that may be present.
• T reat spondylosis on an outpatient basis with 
strict rest and analgesia, possibly acupuncture.
• If overconditioned, recommend weight ­
reduction program.
• Acupuncture—dry needle or electro­
acupuncture treatment at weekly or biweekly 
interval and tapered to as ­needed basis can be 
very effective in relief of pain. Useful in animals 
who do not tolerate medication or when clients 
prefer an alternative treatment modality.
Use only when the patient is exhibiting signs.
(NSAIDs)
• In dogs, NSAIDs are preferable to steroids 
(fewer side effects) unless patient has 
neurologic deficits or concomitant disease 
prohibits use. Administer with food.
• Carprofen (Rimadyl) 2.2 mg/kg PO q12h 
or 4.4 mg/kg PO q24h in dogs.
• Meloxicam (Metacam) 0.2 mg/kg once 
then 0.1 mg/kg q24h in dogs.
• Deracoxib (Deramaxx) 1–2 mg/kg PO 
q24h in dogs.
• Firocoxib (Previcox) 5 mg/kg PO q24h in dogs.
• Grapiprant (Galliprant) 2 mg/kg PO q24h 
in dogs.
• If gastrointestinal sensitivity, use in 
combination with an antacid (famotidine 
0.5–1 mg/kg q24h or omeprazole 0.5–1 mg/
kg q24h) or a gastrointestinal protectant 
(misoprostol at 3–5 μg/kg PO q6–8h or 
sucralfate 0.5–1 g q8h) to reduce the 
possibility of ulceration.Non-NSAID Analgesics
• Use may enable reduction of dose or 
frequency of anti ­inflammatory medications.
• T ramadol 2–5 mg/kg PO q8–12h in dogs; 
1–4 mg/kg q12h in cats.
• Gabapentin 10 mg/kg PO q8–12h in dogs 
or cats.
• Buprenorphine 0.01–0.03 mg/kg PO q8h 
in cats.
• Acetaminophen 5 mg/kg POq12h in dogs.
• Only use in patients with neurologic 
deficits.
• Prednisone 0.25–0.5 mg/kg PO q12h; or 
dexamethasone 0.025–0.05 mg/kg PO q12h.
• Taper to alternate ­day prednisone or 
twice ­weekly dexamethasone.
• Acetaminophen and NSAIDs—do not use 
in cats.
simultaneous use of of NSAIDs and acetami­
nophen, simultaneous use of NSAIDs and 
steroids, use of NSAIDs in patients with gastro  ­ 
intestinal (GI) or renal disease. Doing so decreases 
risk of GI ulceration and renal pathology.
  FOLLOW-UP
• If signs are present, restrict activity and 
gradually return the animal to normal 
activity after signs have subsided for several 
weeks.
• Relapse can occur with strenuous activity.
• With prolonged use of analgesic medications, 
periodic biochemistry testing is warranted.
Boxers—given genetic correlation between 
spondylosis deformans and hip dysplasia and 
potential for early radiographic detection, 
dogs should be screened and selectively bred.
• CT= computed tomography.
• MRI = magnetic resonance imaging.
drug.
Romatowski J. Spondylosis deformans in the 
dog. Compend Contin Educ Pract Vet 
1986, 8:531–536.
Buglione

1282  Blackwell’s Five-Minute Veterinary Consult  
SSporotrichosis
  BASICS
OVERVIEW
• Zoonotic fungal disease affecting the 
integument, lymphatics, or generalized.
• Caused by inoculation of the ubiquitous 
dimorphic fungus Sporothrix schenckii  into 
subcutaneous tissue.
Cat and dog (less common).
SIGNS
• Dogs (cutaneous form)—numerous 
nodules that may drain or crust; most lesions 
located on the head, dorsal muzzle; 
occasionally on the chest, or disseminated on 
the body and on the limbs.
• Cats (cutaneous form)—lesions appear 
initially as wounds or abscesses mimicking 
wounds associated with fighting.
• Cutaneolymphatic form—usually an 
extension of the cutaneous form through the 
lymphatics, resulting in the formation of new 
nodules and draining tracts or crusts; lympha­
denopathy is common.
• Disseminated form—systemic signs 
including lameness, respiratory symptoms 
(nasal discharge, sneezing, stertorous 
breathing), anorexia and weight loss also 
reported in dogs.
• Dogs—hunting dogs from puncture 
wounds associated with thorns or splinters.
• Cats—intact male outdoor cats: Healthy 
cats may have a minor role in sporotrichosis 
transmission
• Animals exposed to soil rich in decaying 
organic debris.
• Exposure to infected animals or clinically 
healthy cats sharing a household with an 
affected cat.
• Immunosuppressive disease.
  DIAGNOSIS
Caution : This is a zoonotic disease and proper 
precautions should be taken to prevent 
exposure; the absence of a break in the skin 
does not protect against the disease. Cats may 
act as reservoirs for S. schenckii  and can 
transmit the infection to humans by a bite or 
scratch.
• Infectious—bacterial (deep) and fungal 
infection (e.g., cryptococcosis, blastomycosis, 
feline leprosy, histoplasmosis).
• Granulomas caused by foreign bodies.
• Parasites— Demodex , Pelodera , Leishmania .CBC/BIOCHEMISTRY/URINALYSIS
None unless associated with generalized 
disease.
• Cultures of affected tissue preferred; swab 
culture may be adequate
• Caution : This is a zoonotic disease; 
laboratory personnel must be warned of the 
potential differential diagnosis.
• Serologic testing and PCR assays are 
• Cytology of exudates—cigar ­ to round ­
shaped yeast found intracellularly or free in 
the exudates with pyogranulamatous 
• Biopsy—organisms usually numerous, 
especially in cats; fungal stains (periodic acid–
Schiff or Gomori’s methamine silver) may aid 
in the diagnosis; the absence of demonstrable 
organisms in tissues from dogs does not 
preclude diagnosis; pyogranulomatous 
inflammation with few mast cells, eosinophils, 
and plasma cells. Radiographs—evidence of 
irregular periostal proliferation.
• Immunohistochemistry might be useful for an 
early diagnosis of sporothricosis in cats. High 
sensitivity reported with immuno  histochemistry 
to diagnose sporothricosis in dogs.
• ELISA— screening tool for the detection of 
specific S. schenckii  antibodies in cats with 
sporotrichosis.
  TREATMENT
Zoonotic; outpatient therapy may be a 
consideration but increases the potential for 
human exposure.
• Dogs—ketoconazole 5–15 mg/kg PO 
q12h, itraconazole 5–10 mg/kg PO q24h, 
terbinafine 30–40 mg/kg PO q24h given 
with food, administered until 1 month after 
clinical resolution; resolution usually occurs 
within 3 months. Disseminated disease—
combination of amphotericin B and 
itraconazole is recommended; terbinafine may 
also be effective.
• Cats—itraconazole 5–15 mg/kg PO q24h 
or divided q12h for a minimum of 1 month 
beyond clinical cure; compounded 
formulations of itraconazole are not 
recommended due to inconsistent absorption.  FOLLOW-UP
Reevaluation, including assessment of liver 
enzymes, recommended every 2–4 weeks.
N/A
• Failure of response to therapy possible.
• Fluconazole and terbinafine remain 
relatively untested but may show promise for 
• Caution : This is a zoonotic disease.
• Client education is of paramount 
importance.
• Absence of a break in the skin does not 
protect against the disease.
• Reports of zoonotic transmission from bites 
and scratches from rodents, parrots, cats, 
dogs, horses, and armadillos.
• Clinically healthy cats sharing a household 
with an infected cat may be a source of 
• ELISA = enzyme ­linked immunosorbent 
assay.
Silva J, Miranda L, Menezes R, et al. 
Comparison of the sensitivity of three 
methods for the early diagnosis of 
sporotrichosis in cats. J Comp Pathol 2018, 
160:72–78.
Putra
Resnick
acknowledge the prior contribution of Holly 
Dutton.

Canine and Feline, Seventh Edition  1283
SSquamous Cell Carcinoma, Digit
  BASICS
OVERVIEW
• Locally invasive malignant tumor usually 
arising from subungual epithelium.
• Cats—metastasis to one or multiple digits 
from primary pulmonary site.
• Dogs—most common digital tumor 
(~50%); up to 25% metastatic rate, up to 
22% multiple digits affected (multicentric 
disease).
• Forelimb more commonly affected than 
hind limb.
• Organ systems—skin/endocrine, musculo- 
skeletal.
• Median age—dogs and cats 10 years; 
reported in dogs as young as 3 years old.
• Large breeds (>75%) and black/dark-coated 
dogs (>90%) predisposed; breeds include 
standard poodle, Labrador retriever, giant 
schnauzer, Rottweiler, dachshund, flat-coated 
retriever, and possibly Beauceron, Briard, and 
miniature poodle.
SIGNS
• Swollen digit or digital mass which fails to 
heal.
• Ulceration.
• Fractured or missing nail.
• Multiple digits affected in up to 22% of 
dogs; may present in one digit and develop 
additional digital tumors later.
• Multiple digits commonly seen in cats 
(30%); due to lung–digit syndrome.
• Regional lymphadenomegaly of the sentinel 
draining lymph node (uncommon at time of 
diagnosis).
Risk factors (dogs)—hereditary; dark skin/
hair pigmentation.
  DIAGNOSIS
• Nailbed infection (paronychia).
• T rauma.
• Other tumors (dog)—melanoma; soft tissue 
sarcomas; mast cell tumor; osteosarcoma.
• Benign lesions—epithelial inclusion cyst, 
keratoacanthoma.
IMAGING
metastatic disease (develops in up to 25% of 
dogs) and rule out a primary pulmonary 
carcinoma (cats).• Limb radiography—lysis of the third 
phalanx of the affected digit in 80% of 
patients with potential secondary extension 
proximally to phalanx 2 and 1.
• Abdominal ultrasonography—for hind 
limb lesions, evaluate intra-abdominal lymph 
nodes for presence of metastatic disease.
• Cytology—diagnostic utility limited if there 
is severe inflammation or secondary infection 
(common), or the tumor is well differentiated.
• Biopsy of lesion—may be needed to 
confirm diagnosis.
• Cytology of regional lymph nodes to 
evaluate for metastasis.
  TREATMENT
• Amputation of the affected digit at the level 
of the metacarpal or metatarsal phalangeal 
joint.
• In cats with a primary pulmonary tumor, 
amputation of a single affected digit may 
provide local palliative care and confirm 
diagnosis, however multiple digits on 
multiple limbs are often affected.
• Palliative radiation can be considered for 
single digits if metastatic disease present or in 
the setting of multicentric/multiple digits 
affected.
• Analgesics for pain control, antibiotics for 
secondary bacterial infections may be 
• Benefit of chemotherapy has not been 
established; however in patients with 
advanced stage of disease chemotherapy 
useful for squamous cell carcinoma of other 
sites could be considered.
Piroxicam—dogs, 0.3 mg/kg PO q24h for 
analgesia/antineoplastic effects; cats, 0.3 mg/
kg PO q24–48h has been used for other 
None
  FOLLOW-UP
Physical exam, thoracic radiographs, lymph 
node evaluation, ± abdominal ultrasound at 
1–2 months, then every 3 months after 
treatment (complete surgical excision).EXPECTED COURSE AND PROGNOSIS
• Complete surgical excision of the primary 
lesion and no evidence of metastasis; 
additional treatment may not be required.
• Survival time following complete surgical 
excision depends upon location of the tumor 
on the digit; squamous cell carcinoma (SCC) 
originating from subungual epithelium: 95% 
1-year and 74% 2-year survival; SCC 
originating in other parts of the digit: 60% 
1-year and 44% 2-year survival.
• In one study 1- and 2-year survival was 
50% and 18%, respectively, while in two 
other studies only 20–45% of dogs died of 
SCC (multicentric or metastatic) and the 
median survival time was not reached.
• Development of multicentric disease 
(multiple affected digits) in dogs appears 
more common than lymph node or 
• Surgery to amputate affected digit, 
regardless of presence of metastases, provides 
positive impact on survival in the dog.
• Histologic grading does not appear 
predictive of development of multicentric or 
metastatic disease in dogs.
• Prognosis for cats is poor with median 
survival times of 2–3 months if metastatic 
from pulmonary carcinoma.
SEE ALSO
• Melanocytic T umors, Skin and Digit.
Belluco S, Brisebard E, Watrelot D, et al. 
Digital squamous cell carcinoma in dogs: 
epidemiological, histological, and 
immunohistochemical study. Vet Pathol 
2013, 50(6):1078–1082.
Author  Alycen P . Lundberg
acknowledge the prior contribution of Jackie 
M. Wypij.

1284  Blackwell’s Five-Minute Veterinary Consult  
SSquamous Cell Carcinoma, Ear
  BASICS
OVERVIEW
• Malignant tumor of squamous epithelium 
occurring on the pinna, external ear, and/or 
middle ear (less common).
• Pinna—most common location in cats; 
tumors of the pinna in dogs are rarely 
• Organ system—skin/endocrine.
• T umors of the pinna—common in cats 
with light pigmentation, average 12 years.
• Ear canal tumors—seen in older dogs and cats.
• Cocker spaniels overrepresented for benign 
and malignant ear canal tumors in one study.
SIGNS
• T umors of the pinna:
◦ Slowly developing lesions of the edge of 
the pinna.
◦ Precancerous stage—crusty eczematous 
lesions (actinic dermatitis).
◦ Cancerous phase—proliferation and/or 
ulceration progresses.
◦ Multiple cutaneous lesions (about 10–15% 
of cats) occur in haired skin (multicentric 
squamous cell carcinoma in situ ).
• T umors of the ear canal:
◦ Often unilateral, arise from the external 
ear canal.
◦ Mass lesion (raised, ulcerated, broad- 
based).
◦ Malodorous aural discharge.
◦ Pruritis.
◦ Pain.
◦ Vestibular signs/Horner’s syndrome 
(facial nerve paralysis, head tilt, circling) in 
~10% of dogs; more common in cats with 
ear canal tumors.
◦ Difficulty opening jaw.
◦ Cervical lymphadenomegaly (retro -
pharyngeal, mandibular).
• Pinna—UV exposure in cats with white fur, 
light skin.
• Ear canal—chronic inflammation may be a 
risk factor.
  DIAGNOSIS
Cats
• Pinna:
◦ T rauma.
◦ Vasculitis.
◦ Cryoglobulinemia.
• Ear canal/middle ear:
◦ Inflammatory/nasopharyngeal polyp 
(middle ear).◦ Other neoplasia (ceruminous gland 
adenocarcinoma, other).
Dogs
• Pinna:
◦ Other neoplasia (mast cell tumor, 
histiocytoma, sebaceous gland tumor).
◦ T rauma.
◦ Chronic otitis.
◦ Other neoplasia (ceruminous gland 
adenoma or adenocarcinoma, papilloma).
◦ Nasopharyngeal polyps (rare).
IMAGING
• Thoracic radiography—evaluate for 
pulmonary metastasis (rare with pinnal lesions).
• CT—shows extent of disease and provides 
surgical planning; 57–67% locally invasive 
into surrounding tissues.
• Cytology may confirm diagnosis; however, 
ulceration, inflammation, and secondary 
infection may limit diagnostic utility.
• Biopsy of pinna/aural mass to confirm 
diagnosis via histopathology; video otoscopy may 
aid in visualization of mass lesion and biopsy.
• Lymph node cytology of draining lymph 
nodes to assess for metastatic disease.
  TREATMENT
• Pinna:
◦ Appropriate surgical excision may require 
pinnectomy and possibly vertical ear canal 
ablation; must remove lesion with margin 
of normal tissue.
◦ Alternatives include photodynamic 
therapy (less predictable; multiple 
treatments may be required), cryosurgery 
(for small, superficial lesions), strontium 
plesiotherapy (superficial radiation 
therapy), electrochemotherapy with 
bleomycin, or curettage/diathermy.
◦ Total ear canal ablation and bulla 
osteotomy is usually needed to achieve 
complete excision; lateral ear canal 
resection rarely achieves adequate 
control.
◦ Radiation therapy may be used for 
palliation of nonresectable tumors or 
postoperatively for microscopic disease.
• Pinna (cat):
◦ Imiquimod 5% cream—apply topically 
q24-48h.◦ Etretinate 0.75–1 mg/kg PO q24h; can 
prevent progression of precancerous lesions; 
may not be commercially available.
◦ Acitretin 1 mg/kg PO q24h can be used 
in place of etretinate.
◦ Vitamin E 400–600 IU PO q12h; may 
be beneficial to prevent or delay progression 
of precancerous lesions.
• Ear canal tumors:
◦ Systemic chemotherapy—benefit not yet 
established; anecdotal benefit.
Women who are pregnant or planning to 
become pregnant should not handle acitretin.
  FOLLOW-UP
• Pinna—physical examination at 1 month, 
then every 3 months after treatment (complete 
surgical excision).
• Ear canal—physical examination, thoracic 
radiographs, lymph node evaluation, and 
possible CT every 3 months after treatment.
• Limit sun exposure.
• Tattoos on nonpigmented areas may be 
helpful.
• Pinna—prognosis good with complete 
surgical excision; survival >1.5 years with 
complete pinnectomy.
• Ear canal tumors locally invasive (57–67%) 
and can recur locally despite surgery; prognosis 
is guarded.
• Dogs—median survival 5.3 months with 
bulla involvement compared to >58 months 
without.
• Cats—median survival 3.8 months; worse 
prognosis with bulla involvement; median 
survival 1.5 months with neurologic signs.
SEE ALSO
• Ceruminous Gland Adenocarcinoma, Ear.
Sula MJ. T umors and tumorlike lesions of 
dog and cat ears. Vet Clin North Am Small 
Anim Pract 2012, 42:1161–1178.
M. Wypij.

Canine and Feline, Seventh Edition  1285
SSquamous Cell Carcinoma, Gingiva
  BASICS
OVERVIEW
• Malignant tumor of squamous epithelium.
• Rapid progression, locally invasive, highly 
osteo-invasive (77%).
• Most common oral malignancy in cats; one 
of most common oral malignancies in dogs.
• Approximately 10–20% metastasis in dogs 
and cats with potential involvement of 
draining lymph nodes (most common) and 
lung parenchyma.
• Mean age (dogs/cats) 10.5 years.
• More common in medium and large-breed 
dogs.
SIGNS
• Mass effect.
• Bloody saliva.
• Hyporexia or avoidance of hard foods/toys.
• Poor grooming (cats).
• Erythematous, ulcerated, fleshy lesion.
• Facial swelling or deformity.
• Exophthalmos.
• Pain on opening jaw.
Potential risk factors in cats include flea collars, 
canned food (tuna), and tobacco smoke.
  DIAGNOSIS
• Other oral malignancy—fibrosarcoma in cats; 
melanoma, fibrosarcoma, osteosarcoma in dogs.
• Epulis (acanthamatous, fibrous, ossifying).
• Benign growth or polyp.
• Gingival hyperplasia (breed, e.g., boxer, or 
drug-induced, e.g., cyclosporine).
IMAGING
• Skull radiography—evaluate potential bone 
• High-detail dental radiography—more 
sensitive in evaluating local disease than skull 
radiography; best with mandibular masses.
• CT—ideal to evaluate soft tissue extension, 
bone invasion, regional lymph nodes, and for 
surgical planning.• Thoracic radiography—evaluate for 
pulmonary metastasis (uncommon in dogs, 
rare in cats).
• Cytology—fine-needle aspirate samples can 
be sufficient, though ulceration, inflammation, 
and secondary infection may limit diagnostic 
utility.
• Deep tissue biopsy—beneficial to differentiate 
from other oral malignancies via histopathology.
• Cytology of regional lymph nodes to assess 
for regionally metastatic disease.
  TREATMENT
Dogs
• Radical surgical excision required (e.g., 
hemi-mandibulectomy); usually well 
tolerated; margins of at least 2 cm necessary.
• Radiation therapy—effective for long-term 
control; curative-intent treatment used alone or 
in combination with surgery or chemotherapy.
• Chemotherapy—alone or in combination 
with other treatment modalities; toceranib 
phosphate (Palladia) exerts single-agent 
activity in a substantial fraction (biologic 
response) of dogs treated.
• Piroxicam may have some antineoplastic effects.
• Cryosurgery or electrochemotherapy—
indicated for small lesions with no bone 
• Photodynamic therapy—adjunct to surgery 
may be effective for local control of small tumors.
• Analgesics for pain or antibiotics for 
secondary bacterial infections may be indicated.
Cats
• Surgery—most tumors are inoperable; 
small rostral lesions may be excised with wide 
2–3 cm margins; cats do not tolerate 
aggressive oral surgery as well as dogs.
• Palliative treatments include coarse-fraction 
radiation therapy (<50% response).
• Metastasis less of a concern as most cats 
succumb to local disease progression.
• Bisphosphonates—used to palliate bone pain.
• Analgesics for pain or antibiotics for secondary 
bacterial infections may be indicated.
• Toceranib phosphate (Palladia)—dogs and 
cats, 2.5–3.25 mg/kg PO q48h.
• Cisplatin—dogs only, 60–70 mg/m2 IV 
once q3–4 weeks for 4 treatments.
• Carboplatin—dogs, 300 mg/m2 q3 weeks 
IV; cats, 180–240 mg/m2 q3–4 weeks for 4–5 
treatments.• Mitoxantrone—cats, 5–6 mg/m2 q3 weeks 
IV for 4–5 treatments.
• Piroxicam—dogs, 0.3 mg/kg PO q24h; 
cats, q48–72h.
Cisplatin—never in cats. Nephrotoxic in 
dogs, cannot combine with NSAIDs.
  FOLLOW-UP
Physical exam, lymph node evaluation, and 
thoracic radiographs at 1–2 months, then 
every 3 months after treatment.
Postoperative complications—tumor 
recurrence, ptyalism, mandibular drift 
causing malocclusion, difficulty prehending 
food, inability to groom.
Dogs
• Negative prognostic factors—caudal or 
maxillary location, >2 cm diameter, older age, 
incomplete excision.
• Surgical excision—median survival 15–16 
months, 34 months combined with radiation 
therapy; mandibulectomy better outcome 
than maxillectomy.
• Combination carboplatin and piroxicam 
with or without surgery—median survival 
>18 months (7 dogs).
• Piroxicam—17% response rate with a median 
progression-free interval of 3.5–6 months.
Cats
• 1-year survival rate is 10% for multimodal 
therapy.
• In rare cases where surgery is an option, 
median survival 1 year.
SEE ALSO
• Melanocytic T umors, Oral.
• Squamous Cell Carcinoma, Tongue.
• Squamous Cell Carcinoma, Tonsil.
Biligic O, Duda L, Sanchez, MD, et al. Feline 
oral squamous cell carcinoma: clinical 
manisfestations and literature review. J Vet 
Dent 2015, 32(1):30–40.
M. Wypij.

1286  Blackwell’s Five-Minute Veterinary Consult  
SSquamous Cell Carcinoma, Lung
  BASICS
OVERVIEW
• Primary tumor of bronchial epithelium 
with squamous metaplasia.
• High metastatic potential to regional lymph 
nodes, pleural surface (carcinomatosis), 
pulmonary parenchyma, less commonly 
distant organs.
• Organ system—respiratory.
• Dog and cat—mean age 11–12 years.
• Persian cats may be overrepresented for 
pulmonary carcinomas.
SIGNS
• May be incidental finding on radiographs.
• Harsh, nonproductive cough.
• Lethargy, exercise intolerance.
• Hemoptysis.
• Cachexia, weight loss.
• Vomiting, regurgitation, diarrhea (cats).
• Lameness:
◦ Distal limb swelling, pain (hypertrophic 
osteopathy).
◦ Digital lesions (cats).
• Urban environment, second-hand smoke 
• Laboratory dogs trained to smoke cigarettes 
develop lung cancer.
  DIAGNOSIS
• Other primary lung neoplasia—adeno -
carcinoma, bronchoalveolar carcinoma, 
histiocytic sarcoma.
• Metastatic pulmonary neoplasia.
• Fungal granuloma.
• Abscess.
Often unremarkable.
IMAGING
• Thoracic radiography (3-view):
◦ Most often in caudal lung lobes.
◦ Often a solitary mass, well-circumscribed 
margins.
◦ May identify tracheobronchial lymphad-
enomegaly, pulmonary metastatic lesions, 
◦ May displace/compress trachea or 
mainstem bronchi.
• CT:
◦ Determines surgical resectability.
◦ Solitary, well-circumscribed, 
bronchocentric mass with internal air bronchograms; mild–moderate 
heterogeneous contrast enhancement.
◦ More sensitive than radiographs in detecting 
pulmonary and lymph node metastasis.
• Limb radiography:
◦ Digit metastases—bony lysis in the distal 
phalanx (cats, lung–digit syndrome).
◦ Hypertrophic osteopathy—periosteal 
proliferation, long bones.
• Cytology:
◦ T ransthoracic fine-needle aspiration of 
peripheral lesions; ultrasound or CT 
guidance may be needed.
◦ Pleural effusion or intrathoracic lymph 
node aspirates if primary lesion is not 
amenable to aspiration.
◦ Endoscopic bronchial brushing may be 
useful for centrally located lesions.
◦ Bronchoalveolar lavage and transtracheal 
wash: rarely diagnostic.
• Biopsy necessary for definitive diagnosis; 
may be obtained via keyhole biopsy, thoraco -
scopy, or thoracotomy.
• Potential complications of diagnostic 
procedures—pneumothorax, hemothorax, 
pleural effusion, infection, and iatrogenic 
tumor seeding (rare).
  TREATMENT
• Surgery—wide and complete resection of 
affected lung lobe; biopsy lymph nodes even 
if they appear normal; lymph node 
extirpation when possible. In select cases, 
thoracoscopic surgery may be considered.
• Chemotherapy—potentially beneficial in 
adjuvant or palliative setting, intracavitary 
(IC) chemotherapy may be useful for carcino -
matosis/pleural effusion.
• Palliative medications—cough suppressants 
and antibiotic therapy for secondary bacterial 
  MEDICATION
• Doxorubicin—dogs >10 kg, 30 mg/m2 IV; 
dogs <10 kg and cats, 1 mg/kg IV q2–3 
weeks for 5 treatments.
• Carboplatin—dogs, 300 mg/m2 IV q3–4 
weeks; cats, 180–250 mg/m2 IV q3–4 weeks 
for 4–5 treatments.
• Mitoxantrone—dogs and cats, 5–6 mg/m2 
q3 weeks; can give IV, IC (if pleural effusion 
present), or split total dose: half IV, half IC 
• Vinorelbine—dogs, 15 mg/m2 IV weekly 
for 4 weeks then every other week for 4 
treatments.• Cisplatin—dogs only, 60 mg/m2 IV q3–4 
weeks for 4 treatments.
• Metronomic chemotherapy—cyclophos-
phamide 15 mg/m2 PO q24h, piroxicam 0.3 
Cisplatin—never use in cats; nephrotoxic in 
dogs.
  FOLLOW-UP
Postoperatively, consider chemotherapy 
options; recheck thoracic radiographs and/or 
CT scan in 1–2 months, then every 3 
months.
• Of the primary pulmonary carcinomas, 
squamous cell carcinoma (SCC) and 
undifferentiated carcinoma carries the worst 
• Survival if untreated or with evidence of 
metastatic disease—usually <3 months.
• Median survival with treatment for SCC— 
8 months (dogs).
• Cats—median survival of pulmonary 
carcinomas surgically excised is 64–156 days.
• Negative prognostic factors (all lung 
tumors)—large size, enlarged lymph nodes, 
metastasis, pleural effusion, high histologic 
grade/poorly differentiated, or respiratory 
signs at diagnosis.
Paraneoplastic hypertrophic osteopathy, 
lung–digit syndrome (cats).
SEE ALSO
Adenocarcinoma, Lung.
Nunley J, Sutton J, Culp W, et al. Primary 
pulmonary neoplasia in cats: assessment of 
computed tomography findings and 
survival. J Small Anim Practice 2015, 
56(11): 651–656.
M. Wypij.

Canine and Feline, Seventh Edition  1287
SSquamous Cell Carcinoma, Nasal and Paranasal Sinuses
  BASICS
OVERVIEW
• Local invasion of neoplastic squamous 
epithelium from the nasal cavity and/or 
paranasal sinuses.
• Slowly progressive (months) and commonly 
• Low metastatic rate.
• Prevalence—15–17% of nasal neoplasia in 
cats and dogs.
• Dogs—median age, 9–10 years, male 
predilection; cats—median 10–12 years, male 
• Dogs—predilection for sinonasal tumors in 
medium and large breeds.
SIGNS
• Intermittent, progressive unilateral to 
bilateral epistaxis and/or mucopurulent nasal 
• Dyspnea.
• Seizures secondary to cribriform plate 
invasion.
• Nasal discharge (epistaxis, mucopurulent, 
and/or serosanguinous).
• Ocular—epiphora, decreased retropulsion, 
elevated third eyelid, exophthalmus.
• Pain on nasal/paranasal sinus palpation.
• Obstructed nasal airflow.
Dolicocephalic breed, urban environment, 
and tobacco smoke exposure speculated to 
be risk factors.
  DIAGNOSIS
• Other intranasal neoplasia—adenocarcinoma, 
undifferentiated carcinoma, lymphoma (cats), 
sarcomas (dogs).
• Cryptococcosis—cats.
• Aspergillosis.
• T rauma.
• Bacterial sinusitis—uncommon.• Lymphocytic—plasmacytic rhinitis.
• Inflammatory polyps (cats).
If epistaxis, perform coagulation profile and 
blood pressure to rule out hypertension and 
coagulopathy prior to intranasal biopsy.
IMAGING
• Skull radiography—asymmetrical osteolysis 
of caudal turbinates; superimposition of soft 
tissue mass; fluid density in the frontal sinuses; 
loss of teeth; displacement of midline 
structures; involvement of hard palate.
• Thoracic radiography—detect pulmonary 
• CT scan—recommended imaging 
modalities for the identification of soft tissue 
density mass, loss of turbinate detail, soft 
tissue/fluid opacity in sinus; best method for 
assessing tumor invasiveness, including bony 
invasion, invasion of cribriform plate or orbit.
• Rhinoscopy—mass effect, may be obscured 
by exudates.
• Cytology—obtained by aspiration or 
squash preparation; may be limited by 
inflammation or secondary infection.
• Biopsy with histopathology—necessary for 
definitive diagnosis; methods include nasal 
hydropulsion, transnostril blind biopsy with 
forceps or bone curette, fiberoptic-guided biopsy, 
percutaneous biopsy of facial deformities; biopsy 
via dental extraction site, rhinotomy.
• Precautions must be taken to minimize risk 
of penetrating the cribriform plate.
• Cytology and/or biopsy of regional lymph 
nodes—detect metastatic disease 
  TREATMENT
• Definitive radiotherapy—best clinical 
control in dogs and cats; exenteration does 
not add benefit.
• Coarse-fraction radiotherapy beneficial in 
dogs and cats for palliation.
• Adjunctive chemotherapy—responses in 
dogs reported; recommended for palliation of 
clinical signs, metastasis, and as an adjuvant 
to radiation therapy.
• Anecdotally, nasal hydropulsion may 
palliate clinical signs.
• Cisplatin—dogs only, 60–70 mg/m2 IV q3 
weeks for 4 treatments.• Carboplatin—dogs, 300 mg/m2 IV q3 
• Mitoxantrone—dogs/cats, 5–6 mg/m2 IV 
q3 weeks for 4–5 treatments.
• Toceranib phosphate (Palladia)—dogs/cats, 
2.5–3.25 mg/kg PO q48h.
• Piroxicam—0.3 mg/kg PO q24h (dogs), 
q48h (cats).
• Cisplatin—never use in cats; nephrotoxic in 
dogs—do not administer with NSAIDs.
  FOLLOW-UP
lymph node evaluation, ±CT scan every 
3 months after treatment or when signs recur.
Acute or late side effects from radiation therapy.
• Untreated carcinomas (all types)—median 
survival 3 months; epistaxis carries a worse 
• Definitive radiotherapy (all carcinomas)—
median survival 12–18 months (dogs and cats); 
10.4 months with stereotactic radiotherapy.
• Coarse-fraction radiation therapy (all tumor 
types)—improved clinical signs in ~90% of 
dogs; median survival 4.8–10 months; median 
survival 10–12 months (cats).
• Local recurrence with extension to the brain 
can occur.
• Re-irradiation is possible, reduces clinical 
signs, extends survival time.
SEE ALSO
Adenocarcinoma, Nasal.
Fujiwara A, Kobayashi T, Kazato Y, et al. 
Efficacy of hypofractionated radiotherapy 
for nasal tumours in 38 dogs (2005–2008). 
J Small Anim Pract 2013, 54(2):80–86.
M. Wypij.

1288  Blackwell’s Five-Minute Veterinary Consult  
SSquamous Cell Carcinoma, Nasal Planum
  BASICS
OVERVIEW
• Malignant tumor of squamous epithelial 
cells of the nasal planum.
• Locally invasive and rarely metastasizes.
• Organ systems—skin/exocrine, respiratory.
• Common in cat; rare in dog.
• Mean age—cats, 8.5–12.1 years; dogs, 
9–10 years.
• More likely to develop in animals with a 
lightly pigmented nose (cats).
• No reported sex or breed predilection in cats.
• Dogs—overrepresentation of males and 
Labrador retrievers in one study.
SIGNS
• Cats—slowly progressive lesion; may begin as 
superficial crusting and scabbing, progress to 
carcinoma in situ , and develop into superficial and 
then invasive erosive carcinoma; other cutaneous 
sites may be affected (cats—multicentric 
squamous cell carcinoma in situ  [MSCCIS]).
• Dogs—sneezing; epistaxis; swelling and 
ulceration of planum, proliferative lesion.
• Exposure to ultraviolet light (UVB).
• Absence of protective pigment (cats).
  DIAGNOSIS
• Infection/abscess.
• T rauma.
• Dermatitis (allergic, other).
• Eosinophilic granuloma complex (cats).
• Cutaneous lymphoma.
IMAGING
• CT scan—evaluate soft tissue extension and 
bone invasion prior to surgical planning, 
essential for canine tumors in which extensive 
underlying structures are often involved.
• Cytology—fine-needle aspirate of primary 
lesion may confirm diagnosis; however, 
• Biopsy and histopathology—a deep wedge 
or punch biopsy is often needed to definitively 
diagnose squamous cell carcinoma. Multiple 
samples recommended as lesion may have a 
spectrum of actinic changes ranging from 
squamous metaplasia to invasive carcinoma.• Cytology or histopathology of regional 
lymph nodes screening for regional metastasis 
(rare in cats, occasional in dogs).
Lesions may vary in appearance depending on 
stage of disease in cats; typically ulcerative in 
cats; more likely proliferative in dogs.
  TREATMENT
• Superficial tumors—surgery, cryosurgery, 
irradiation (strontium-90 plesiotherapy), 
photodynamic therapy, electrochemother -
apy with bleomycin, or curettage/diathermy.
• Invasive tumors—require radical surgical 
excision and adjunctive external beam 
radiotherapy (cats); dogs not as responsive to 
radiotherapy.
• Immediate postoperative nutritional 
support may be required, especially for cats.
• Analgesics for pain control and antibiotics 
for secondary bacterial infections as 
• Etretinate—cats, 0.75–1 mg/kg PO q24h; 
synthetic retinoid; may be useful for early 
precancerous lesions; may not be commercially 
• Acitretin—cats, 1 mg/kg PO q24h can be 
used in place of etretinate.
• Imiquimod 5% cream for nasal planum 
lesions associated with MSCCIS—apply 
topically to affected lesions q24–48h; most 
cats respond but develop new lesions in other 
sites; these lesions often subsequently respond 
to topical therapy.
become pregnant should not handle 
etretinate, acitretin, or imiquimod.
  FOLLOW-UP
• Physical examination at 1 month, then 
• Biopsy any new suspicious lesion.
helpful.
• Prognosis—good for small, noninvasive 
tumors; guarded for invasive tumors.• Survival with radiotherapy alone (cats)—
mean 17.7 months; 1 year, 61.5% with 
81.8% recurrence.
• Surgery (cats, nosectomy)—median survival 
>22 months.
• Strontium-90 plesiotherapy (cats, superficial)—  
98% response rate; median progression-free 
interval of 4.5 years; median survival >8 years.
• Photodynamic therapy (cats, superficial)— 
96% response rate; often need multiple 
treatments; does not appear as effective as 
other therapies long term.
• Electrochemotherapy with bleomycin—risk 
of recurrence; many achieve complete 
• Curettage and diathermy—excellent 
response; risk of recurrence.
• Dogs (superficial tumors)—surgery alone 
may be curative.
• Dogs (invasive tumors)—in one study of 8 
dogs, average survival time was 5.4 months; 
in another study of 17 dogs treated with 
surgery and/or radiation therapy, 70% of 
tumors recurred with a median survival time 
of 3–6 months.
SEE ALSO
• Squamous Cell Carcinoma, Ear.
• MSCCIS = multicentric squamous cell 
carcinoma in situ .
Jarrett RH, Norman EJ, Gibson IR, Jarrett P . 
Nose and nasal planum neoplasia, recon-
struction. Vet Clin North Am Small Anim 
Pract 2016, 46(4):735–750.
M. Wypij.

Canine and Feline, Seventh Edition  1289
SSquamous Cell Carcinoma, Skin
  BASICS
OVERVIEW
• Multicentric squamous cell carcinoma in 
situ (MSSCIS)- also called Bowen’s-like 
disease or Bowenoid carcinoma in situ  (cats).
• Local disease may progress from carcinoma 
in situ  to invasive carcinoma.
• Metastasis is uncommon—most common 
sites are regional lymph nodes and lungs.
• Represents 9–25% of all skin tumors in 
cats; 4–18% in dogs.
• Solar-induced (actinic) SCC is more 
prevalent in sunny climates and high altitudes.
• Cats, mean age 9–10 years; often have 
light/unpigmented skin.
• Dogs, mean age 8 years; Scottish terrier, 
Pekingese, boxer, poodle, Norwegian 
elkhound, Dalmatian, beagle, whippet, and 
white English bull terrier may be predisposed.
SIGNS
• Proliferative or erosive skin lesions.
• Solar-induced lesions in cats—nasal 
planum, eyelids, lips, and pinna.
• MSCCIS may occur in any site, unrelated 
to sun exposure or skin pigmentation; may 
note 2–30+ lesions on the head, digits, neck, 
thorax, shoulders, and ventral abdomen; hair 
in the lesion epilates easily; crusts cling to the 
epilated hair shaft.
• Dogs—most commonly affects toes, 
scrotum, nose, legs, and anus.
• Ultraviolet irradiation (actinic form).
• Papillomaviruses may play a role.
• Light/nonpigmented skin.
• Previous thermal injury.
• Risk factors for MSCCIS in cats are 
undetermined but may be associated with 
  DIAGNOSIS
• T rauma.
• Thoracic radiography—may detect lung 
• Abdominal ultrasonography—evaluate and 
monitor sublumbar lymph nodes if skin 
disease involves the caudal half of the patient.
• Cytology or histopathology of lesion—
infection may limit diagnostic utility of 
cytology. A deep wedge or punch biopsy is 
often needed to definitively diagnose 
cutaneous SCC. Multiple samples recom -
mended as actinic form may encompass 
spectrum from actinic changes to 
• Cytology of lymph nodes to identify 
presence of regional metastasis.
  TREATMENT
• Superficial tumors suspected to be 
solar-induced—wide surgical excision may be 
locally curative; other treatment options 
include cryosurgery, photodynamic therapy, 
or strontium-90 plesiotherapy.
• Invasive tumors—require aggressive surgical 
excision, external-beam radiation therapy has 
shown effectiveness.
• MSCCIS may be treated with curative-
intent surgery for local control; however, 
most cats develop new lesions in other sites; 
treatment with immune-modulating drugs 
(imiquimod) may be most effective.
• Adjunctive chemotherapy—recommended 
with incomplete surgical excision, nonresect-
able mass, and metastasis.
• Electrochemotherapy (bleomycin) and 
curettage with diathermy may be effective.
• Analgesics as needed.
• Antibiotic therapy if secondary skin 
• Discuss UV risk factors associated with the 
development of the tumor.
• Most cats with MSCCIS will develop new 
lesions in other sites.
• Imiquimod 5% cream for MSCCIS—topi-
cally to affected lesions q24–48h; most cats 
respond but develop new lesions in other 
sites.
• Cisplatin—dogs, 60 mg/m2 IV q3 or 4 
weeks; cats, 200–250 mg/m2 IV q3–4 weeks 
IV q3 weeks for 4–5 treatments.
Cisplatin—never use in cats; nephrotoxic in dogs.
Topical synthetic retinoids (e.g., tretinoin)- 
may be useful for early solar-induced 
superficial lesions; may be irritating to skin.
  FOLLOW-UP
• Physical examination 1 month after 
resolution of tumor, then every 3 months 
after treatment.
• Thoracic radiography and lymph node 
evaluation at each 3-month recheck examina-
tion; abdominal ultrasound if the lesion is on 
the caudal portion of the patient.
• Tattoos on nonpigmented areas may be helpful.
Prognosis—good with superficial lesions that 
receive appropriate treatment; guarded with 
invasive lesions, advanced stage of disease, or 
recurrent lesions.
SEE ALSO
Murphy S. Cutaneous squamous cell 
carcinoma in the cat: current understanding 
and treatment approaches. J Feline Med 
Surg 2013, 15(5):401–407.
M. Wypij.

1290  Blackwell’s Five-Minute Veterinary Consult  
SSquamous Cell Carcinoma, Tongue
  BASICS
OVERVIEW
• Rare tumor that occurs more commonly in 
cats than in dogs.
• Usually grows rapidly.
• Cats—most common lingual neoplasia, 
often progresses locally prior to clinical 
evidence of metastasis.
• Dogs—one of most common malignant 
lingual neoplasias (25–32%); variably 
metastatic by way of lymphatic vessels to 
regional lymph nodes and lungs (0–43%).
• Organ system—gastrointestinal.
• Cats—middle-aged or older (>7 years).
• Dogs—average 10–11 years; female 
large-breed dogs most commonly affected.
SIGNS
• Oral bleeding.
• Decreased appetite.
• Incidental finding.
• Tongue mass—variable appearance, often 
nodular and ulcerated.
• Intramandibular swelling (cats).
• Cervical lymphadenomegaly—occasionally.
Potential increased risk of feline oral squamous 
cell carcinoma (SCC) associated with flea 
collars, canned food (particularly tuna), and 
possibly exposure to tobacco smoke.
  DIAGNOSIS
• Other lingual malignancy (melanoma, sarcoma, 
mast cell tumor, plasmacytoma, lymphoma, 
hemangiosarcoma, granular cell tumor).
• T rauma.
• Ulcerative glossitis.
• Benign lesion (papilloma).
IMAGING
• Advanced imaging with CT or MRI 
provides greatest information regarding extent 
of disease.• Thoracic radiography—three-view required 
to evaluate lungs for metastasis; more 
• Cytology—fine-needle aspirate or 
impression smear from incisional biopsy 
(wedge); may yield diagnosis; however, 
• Deep wedge tissue biopsy—necessary for 
• Cytology and/or lymph node biopsy to 
evaluate for regional metastasis; more 
  TREATMENT
• Surgical—generally inoperable in cats; 
aggressive excision warranted in dogs; 
function of the tongue after recuperation is 
usually acceptable in dogs, but will require 
changes in husbandry practices.
• Postsurgical care (e.g., esophagostomy) by 
owner often required.
• Partial glossectomy—may be performed on 
the rostral half (mobile tongue) or longitudinal 
half of the tongue (40–60% removed); 
~35–50% of patients have incomplete 
surgical margins.
• Subtotal glossectomy may be considered in 
select cases.
• Other surgical methods (e.g., electrocautery 
and cryosurgery) do not offer additional 
advantage to conventional excision.
• Response to radiotherapy—poor (<7 weeks); 
may be used adjunctively on micro  scopic 
disease postoperatively.
• Systemic therapies—chemotherapy agents 
or toceranib phosphate effective in oral 
SCC may exert anticancer activities for 
lingual SCC.
• Piroxicam may have antineoplastic activity 
• Supportive/palliative medications for 
analgesia and antibiotics for secondary 
for 4- 5 treatments.
cats, 0.3 mg/kg PO q48h.
cats, 2.5–3.25 mg/kg PO q48h.CONTRAINDICATIONS/POSSIBLE 
N/A
  FOLLOW-UP
After complete surgical resection, recheck at 
1–2 months and then every 3 months with 
physical examination and evaluation for 
metastasis (lymph node palpation/aspiration 
and thoracic imaging).
Possible complications postoperatively—long-
term difficulty prehending food, local 
• Prognosis—poor, owing to extensive local 
disease (cat) and local recurrence (28% for all 
lingual tumors) and moderate rate of 
metastasis (dog).
• After surgical excision (subtotal glossectomy, 
dogs)—median survival 216 days, <25% 
survive 1 year.
• Negative prognostic factors (dogs)—caudal 
location, incomplete excision, recurrence, 
larger size (>2 cm); histologic grade, 
• Piroxicam—17% response rate in oral SCC 
with a median progression-free interval of 
3.5–6 months; one partial response in 3 dogs 
with lingual SCC.
• Prognosis in cats similar to other oral sites 
of SCC; median survival ~3 months with 
multimodal therapy.
SEE ALSO
• Squamous Cell Carcinoma, Gingiva.
Culp WT, Ehrhart N, Withrow SJ, et al. 
Results of surgical excision and evaluation 
of factors associated with survival time in 
dogs with lingual neoplasia: 97 cases 
(1995–2008). J Am Vet Med Assoc 2013, 
242(10):1392–1397.
M. Wypij.

Canine and Feline, Seventh Edition  1291
SSquamous Cell Carcinoma, Tonsil
  BASICS
OVERVIEW
• Rapid and progressive invasion of neoplastic 
squamous epithelium arising from the 
tonsillar fossa into tonsillar lymphoid tissue.
• More common in dogs than cats—
comprises 9% of canine oral tumors.
• Highly locally invasive into soft tissues.
• Early metastasis—70–90% eventually 
metastasize regardless of local control.
• Dog and cat; median age 10 years.
• No known breed or sex predilection.
SIGNS
• Cough.
• Enlarged lymph nodes.
• Retching.
• Enlarged tonsil(s).
• Widening or “fullness” of oropharyngeal space.
• Cervical lymphadenomegaly.
Exact cause unknown; however, 10 times 
more common in animals living in urban 
environments vs. those in rural environments.
  DIAGNOSIS
• Lymphoma (generally associated with 
lymphadenomegaly and bilateral disease).
• Abscess.
• Metastatic neoplasm (oral melanoma, 
sarcoma).
• Tonsillitis.
• Tonsillar crypt foreign body.
• Salivary gland tumor.
• Thyroid carcinoma.
IMAGING
• Thoracic radiography—three-view to detect 
lung metastasis; 5–20% positive for metastasis 
at presentation; 60–85% metastasis at death.
• CT—evaluate local extension of primary 
tumor as well as mandibular and retropharyngeal lymph node involvement; recommended prior 
to surgery or radiation therapy.
• Abdominal ultrasound—evaluate 
abdominal organs; 20% disseminated 
metastasis to multiple organs at death (dogs).
• Cytology—inflammation and secondary 
fine-needle aspirate samples but should still 
be attempted.
• Histopathology—deep tissue biopsy may be 
needed to differentiate from other oral 
nodes to evaluate for metastatic disease; in 
dogs 20–55% metastasis at diagnosis.
  TREATMENT
• Surgery—many are inoperable; tonsillec -
tomy, when done, should be bilateral.
• Postoperative care (esophagostomy or 
gastrotomy tube) by owner may be needed.
• Other surgical methods (electrocautery and 
cryosurgery)—no advantage over conventional 
excision.
• Regional radiation therapy is effective for 
local control and palliation of clinical signs.
• Chemotherapy—anecdotal reports of 
cisplatin, carboplatin, doxorubicin being used 
with limited success.
• Piroxicam and/or toceranib phosphate 
(Palladia) may have antineoplastic effects in 
canine carcinomas.
• Analgesics for pain control; antibiotics for 
weeks; cats, 180–240 mg/m2 IV q3–4 weeks 
IV q2–3 weeks for 5 treatments.
• Piroxicam—dogs, 0.3 mg/kg PO q24h, 
toceranib phosphate (Palladia) 2.75–3.25 mg/
kg PO q48h.
dogs <10 kg and cats, 1 mg/kg q2–3 weeks 
for 5 treatments.
• Cisplatin—dogs, 60–70 mg/m2 IV q3–4 
Cisplatin—never use in cats; nephrotoxic in dogs.  FOLLOW-UP
Most patients euthanized within months for 
local progression or metastasis; patients with 
curative-intent therapies should be rechecked 
with physical examination and evaluated for 
metastasis (thoracic radiographs/CT) at 1–2 
months, then every 3 months.
recurrence, may need feeding tubes 
• Prognosis—poor owing to extensive local 
disease and high rate of recurrence (tongue, 
pharynx, lymph nodes) and metastasis.
• Minimal information in cats; however, 
appear to carry a grave prognosis as with most 
oral squamous cell carcinomas in cats.
• Dogs: 11–40% 1-year survival (survival 
times increased if unilateral and no metastasis 
at diagnosis).
• Untreated (dogs) median survival 1–2 
months vs. treated median survival 7–8 
months.
• Surgery alone has limited benefit—median 
survival 2–4 months (dogs).
• Palliative radiotherapy or chemotherapy 
(dogs)—75% response rate, 2–9 months 
median survival.
• Surgery, radiation therapy, and chemotherapy 
(dogs)—median survival 9–12 months.
• Piroxicam alone—17% response rate for all 
oral squamous cell carcinoma with a median 
progression-free interval of 3.5–6 months; 3 
of 5 dogs with tonsillar SCC exhibiting a 
partial remission or stable disease.
SEE ALSO
Grant J, North S. Evaluation of the factors 
contributing to long-term survival in canine 
tonsillar squamous cell carcinoma. Aust Vet 
J 2016, 94(6):197–202.
M. Wypij.

1292  Blackwell’s Five-Minute Veterinary Consult  
SStaphylococcal Infections
  BASICS
OVERVIEW
• Staphylococcus —Gram-positive, nonmotile, 
facultatively anaerobic, spherical bacteria 
(cocci); staphyle  (Greek “bunch of grapes”) 
form characteristic microscopic arrangement 
in clusters.
• Results in variety of infections characterized 
by pus formation.
• Can produce toxins (superantigens) that 
exert profound systemic signs (fever, hypoten -
sion, shock, multiorgan failure, death).
• Ubiquitous; live free in environment and as 
commensal parasites of skin and upper 
respiratory tract.
• Pathogenic and nonpathogenic strains; wide 
spectrum of virulence, host range, and site 
specificities; not strictly host- or site-specific.
• Pathogenic strains—possess extracellular 
toxins and enzymes (e.g., coagulase, staphylo -
kinase, hemolysin, epidermolysins); staphylo-
coagulase in more pathogenic strains (e.g., 
S. pseudintermedius , S. aureus ).
• Coagulase-negative staphylococci are less 
virulent (e.g., S. felis , S. epidermidis ).
• Methicillin-resistant staphylococci, which are 
increasingly isolated from dogs and cats, is an 
emerging problem due to multidrug resistance 
phenotype which limits treatment options and 
challenges infection control measures. When a 
methicillin-resistant strain expresses co-resistance 
to at least two additional antimicrobial classes 
then it is called multidrug resistant (MDR).
• Very young—susceptible because of 
incomplete, developing immunity.
• Old, debilitated—susceptible because of 
impaired host defenses.
• Immunocompromised—more susceptible.
SIGNS
• Abscesses and infections of the skin, eyes, 
ears, respiratory system, genitourinary tract, 
skeleton, and joints.
• Dogs—pyoderma, otitis externa, cystitis, 
prostatitis, pneumonia, abscesses, osteomyeli-
tis, discospondylitis, arthritis, mastitis, 
bacteremia, endocarditis, wound infections, 
toxic shock syndrome.
• Cats—abscesses, oral infections, otitis 
externa, conjunctivitis, metritis, cholangio-
hepatitis, cystitis, bacteremia.
• Fever.
• Pain.
• Can affect every organ system.
• Opportunistic pathogens depending on 
virulence factors:⚬ Adhesion expression (binds bacteria to 
cells and extracellular matrix).
⚬ Toxins (cytolytic, exfoliative, enterotoxi-
genic, superantigen toxins).
⚬ Expression of factors to evade the host’s 
immune response (e.g., coagulase).
⚬ Formation of biofilms which protect the 
bacterium from the immune response.
• Disease—from disturbance of the natural 
host–parasite equilibrium when local and 
general defense mechanisms are significantly 
lowered (e.g., chronic debilitating diseases).
• Secondary infection—allergies (atopy, food, 
fleas); endocrinopathies (hypothyroidism, 
hyperadrenocorticism); parasites (demodi -
cosis); seborrhea.
• Burns or wounds—complications.
• Biofilms (extracellular polysaccharide 
networks) support infection of implants and 
invasive devices (e.g., IV catheters).
• T ransmission—airborne organisms, carriers, 
direct contact (droplet nuclei).
• S. pseudintermedius —most common 
staphylococcal species isolated from dogs, 
commensal organism on skin and mucous 
membranes of dog and cat (although much 
lower prevalence in cats). Methicillin-resistant 
S. pseudintermedius  (MRSP) is a clinically 
important pathogen causing antibiotic 
resistant infections in dogs and cats (see 
Multidrug Resistant Infections).
• S. aureus —does not colonize dogs as often as 
S. pseudintermedius ; colonizes skin and mucosal 
membranes of humans where it is one of the 
most common community-acquired and 
hospital-acquired pathogens of people. 
Methicillin-resistant S. aureus  (MRSA) infections 
uncommonly diagnosed in dogs and cats.
• S. schleiferi —coagulase variable species; 
rarely isolated from healthy skin of dogs or 
cats but commonly isolated from skin and ear 
canal infections of dogs with history of prior 
antimicrobial exposures.
• Risk factors for methicillin-resistant 
staphylococcus in dogs include previous 
antibiotic therapy, previous hospitalization, 
urban environment, older age.
  DIAGNOSIS
• Dermatitis—allergies, seborrhea, parasites, 
immune-mediated.
• Other infectious causes—viruses, bacteria, 
fungi, Rickettsia , protozoa.
• Immune-mediated diseases.
• Normal or high white blood cells (WBCs) 
consisting of neutrophilia ± left shift.
• Biochemistry—may suggest predisposing 
cause.• Urinalysis—pyuria (with or without 
bacteruria) with cystitis.
• Direct microscopy.
• Gram stain.
• Cytology—neutrophils and cocci singly or 
in pairs, short chains, or irregular clusters.
• Culture—avoid superficial contamination; 
collect samples by aspiration, wash, or biopsy; 
do not overinterpret a positive isolation; 
organisms can be isolated from normal animals
• Organisms survive up to 48 hours in 
clinical specimens when kept cool (4°C/40°F), 
particularly on swabs containing a holding 
medium.
• Antibiotic susceptibility testing (very 
important due to methicillin-resistant and 
multidrug-resistant staphylococci).
• Pulsed-field gel electrophoresis molecular 
typing.
IMAGING
Radiology—osteolytic and osteoproliferative 
lesions with osteomyelitis; interstitial or 
alveolar pulmonary pattern with pneumonia; 
radiodense uroliths (struvite). Endocarditis 
lesions may be visible by echocardiography. 
Ultrasonography may identify abscesses.
Cerebrospinal fluid tap—if meningitis or 
discospondylitis suspected; discospondylitis 
lesions may be fine-needle aspirated using CT 
or ultrasound guidance.
Characteristic abscess lesion—necrotic tissue, 
fibrin, and a large number of neutrophils.
  TREATMENT
• Identify and manage predisposing cause to 
minimize selection for antibiotic-resistant 
staphylococci.
• Properly handle and dispose of contami-
nated objects, practice good hand hygiene 
and wear personal protective equipment 
(PPE) when handing patient with known or 
suspected methicillin-resistant staphylococcus 
• Topical antibacterial cleaning of wounds 
and pyoderma—chlorhexidine, benzoyl 
peroxide shampoos.
• Known or suspected methicillin-resistant 
staphylococcus-infected animals should be 
isolated.
• Antibiotic resistance—great propensity 
owing to production of β-lactamase, which

Canine and Feline, Seventh Edition  1293
Sinactivates penicillins; may carry plasmids 
(segments of genetic material that may carry 
genes for antimicrobial resistance) that can be 
transferred to other strains of staphylococci or 
species of bacteria.
• History of previous antimicrobial therapy 
for staphylococcal infection—culture and 
antibiotic susceptibility testing indicated: 
choose drugs below based on this testing.
• Use topical therapy when possible.
• Non-penicillinase-producing strains:
⚬ Penicillin G 10,000–20,000 U/kg IM, SC 
q12–24h, penicillin V 8–30 mg/kg PO q8h.
⚬ Amoxicillin 22 mg/kg PO q6–8h or 
ampicillin 22–30 mg/kg IV, IM, SC q6–8h.
• Penicillinase-producing strains:
⚬ First-generation cephalosporins—
cephalexin at 22 mg/kg PO q8h; cefadroxil 
at 22 mg/kg PO q8–12h.
⚬ β-Lactamase-resistant synthetic penicil-
lins—clavulanic acid-potentiated amoxicil-
lin 20–25 mg/kg PO q8–12h, oxacillin 
22–40 mg/kg PO q8h, dicloxacillin 10–25 
mg/kg PO q8h).
• Gentamicin 2–4 mg/kg IV, IM, SC q8h or 
amikacin 15 mg/kg IV q24h.
• T rimethoprim-potentiated sulfonamides— 
30 mg/kg IV, PO q12h.
• Chloramphenicol—40–50 mg/kg IV, IM, 
• Methicillin-resistant staphylococci express 
mecA  gene which encodes an altered 
penicillin-binding protein (PBP-2a) which 
has a low affinity for all β-lactam drugs 
(penicillins, cephalosporins, and 
carbapenems).
• In patients with penicillin allergy—try 
cephalosporin, clindamycin, enrofloxacin, or 
vancomycin (although this is strongly 
discouraged to reserve vancomycin for treatment of serious MRSA infections in 
humans).
Avoid immunosuppressive drugs.
  FOLLOW-UP
As appropriate for location of infection
• Possible; MRSA is also potential 
anthropozoonosis.
• Most people and pets carry their own 
pathogenic staphylococcal flora; disease is not 
caused by mere exposure; however, transfer 
from dogs to humans is possible, and vice 
versa.
• Bite infections contain a mix of aerobes and 
anaerobes from both the skin of the patient 
and the mouth of the animal, including 
Staphylococcus .
• Hand hygiene (proper washing/drying and 
use of alcohol-based hand sanitizers) and use 
of PPE is an integral part of the prevention of 
the spread of MRSA/MRSP between animals 
and MRSA between animals and humans.
• Owners of dogs and cats with MRSA 
infection should be educated to wash their 
hands after handling their pets, to clean and 
disinfect surfaces that might become 
contaminated, and to not let their pet lick 
their face or open wounds. If owners have 
concerns about their health or the health of others in their household then they should be 
instructed to talk to their health care 
provider.
• MDR = multidrug resistant.
aureus .
• MRSP = methicillin-resistant Staphylococcus 
• PPE = personal protective equipment.
www.cdc.gov/mrsa
Béco L, Guaguère E, Lorente Mendez C, 
et al. Suggested guidelines for using 
systemic antimicrobials in bacterial skin 
infections (2): antimicrobial choice, 
treatment regimens and compliance. Vet 
Rec 2013, 172:156–160.
Cain CL. Antimicrobial resistance in 
staphylococci in small animals. Vet Clin 
Small Anim 2013; 43:19–40.
Davis JA, Jackson CR, Fedorka-Cray PJ, et al. 
Carriage of methicillin-resistant staphylo-
cocci by healthy companion animals in the 
US. Lett Appl Microbiol 2014, 59:1–8.
Morris DO, Loeffler A, Davis MF , et al. 
Recommendations for approaches to 
meticillin-resistant staphylococcal infections 
of small animals: diagnosis, therapeutic 
considerations and preventative measures. 
Vet Dermatol 2017, 28:304–331.
Sykes JE. Staphylococcus infections. In: Sykes 
347–354.
Consulting Editor  Amie Koenig(continued)  Staphylococcal Infections

1294  Blackwell’s Five-Minute Veterinary Consult  
SSteroid-Responsive Meningitis-Arteritis—Dogs
  BASICS
OVERVIEW
• May be acute or protracted.
• Lesions—most impressive in CNS, 
affecting meninges and meningeal arteries; 
sometimes peracute bleeding; vascular 
changes in the heart, liver, kidney, and 
gastrointestinal system.
• Genetic factors—play a role in different 
breeds such as beagles and Nova Scotia duck 
tolling retrievers.
• Worldwide occurrence.
• Dog.
• Beagle, Bernese mountain dog, Nova Scotia 
duck tolling retriever, and boxer predisposed; 
any breed can be affected.
• Mostly young adult dogs of both sexes; age 
range 5–18 months.
SIGNS
• Classical (acute)—hyperesthesia; cervical 
rigidity; stiff gait; fever up to 42°C (107.6°F).
• Protracted—neurologic deficits, usually 
reflecting a spinal cord or multifocal lesion.
• Pathologic findings, laboratory data, and 
marked response to steroids—suggest an 
immune-mediated disease related to a 
dysregulation of IgA production and a 
Th17-skewed immune response.
• Epidemiologic observations—altered 
immune response may be triggered by an 
environmental factor, possibly of infectious 
nature; genetic predisposition.
  DIAGNOSIS
• Acute—bacterial meningitis; meningeal 
tumors; discospondylitis.
• Protracted—bacterial meningitis; meningeal 
tumors (histiocytosis, meningioma, lymphosar -
coma); other infectious encephalitides; 
meningoencephalomyelitis of unknown origin.
• Acute—leukocytosis with neutrophilia and 
left shift.
• Protracted—CBC noncontributory.
IgA levels (serum and CSF)—usually high; 
high serum C-reactive protein (CRP) levels.
IMAGING
Radiographs to exclude discospondylitis; 
MRI to exclude differential diagnoses.DIAGNOSTIC PROCEDURES
• Acute—mild-to-moderate elevation of 
protein; moderate-to-marked pleocytosis, 
predominantly polymorphonuclear cells.
• Protracted—normal, or mild elevation of 
protein; mild-to-moderate pleocytosis with 
mixed cell population, or with a predomi-
nance of mononuclear cells.
Acute
• Marked meningitis with macrophages, 
plasma cells, lymphocytes, and varying 
numbers of polymorphonuclear cells mostly 
in the cervical region.
• Lesions of the meningeal arteries—
degenerative with perivascular inflammation.
Protracted
• Marked fibrous thickening and focal 
mineralization of the leptomeninges.
• Arterial walls—thickened and stenotic from 
cellular proliferation of the intima and 
fibrosis.
  TREATMENT
• Inpatient—at onset, fluid therapy and ice 
packs useful for high body temperature.
• After initial treatment, managed as 
• Regular follow-ups—inform client about 
side effects of long-term steroid treatment.
• Initial signs with mild CSF pleocytosis—
(NSAIDs); carefully monitor the patient.
• First relapse, or symptoms become worse 
with marked CSF pleocytosis—start 
long-term treatment (6 months) with 
prednisolone 4 mg/kg PO q24h for 1–2 days; 
then taper slowly; reexamine patient (CSF 
collection, blood profile or CRP) every 4–6 
weeks after initiation of therapy.
• Neurologic examination and CSF become 
normal, normal serum CRP levels—reduce 
steroid dose.
• Persistent pleocytosis—continue same 
steroid dosage.
• T reatment may be stopped after about 6 
months.
• Immunosuppressive drugs if patient does 
not respond well to prednisolone alone; used 
in combination.
• Consider gastrointestinal protector to avoid 
ulcer.CONTRAINDICATIONS/POSSIBLE 
Corticosteroids—high-dose treatment can 
lead to severe complications; non-life-
threatening side effects (polyuria, polydipsia, 
polyphagia, and weight gain); not tolerated in 
about 5% of dogs.
  FOLLOW-UP
Control examinations—every 4–6 weeks; 
include blood examination and CSF 
collection; measurement of serum CRP levels 
until steroids discontinued.
Strictly control treatment schedule to prevent 
frequent relapses. No reliable predictive 
indicator available for relapse.
• Subarachnoid bleed—may result in acute 
tetra- or paraplegia.
• Hypoxic lesions of spinal cord or brain.
• Side effects of immunosuppressive 
• Acute—prognosis relatively good in young 
dogs with early therapy.
• Protracted cases with frequent relapses—
prognosis guarded; controlled studies note 
about 60% of dogs are cured after immuno-
suppressive treatment. Relapses occur in 
about 32% of the dogs.
Old animals do not tolerate long-term steroid 
treatment well, but condition rare in dogs >5 
SYNONYMS
• Aseptic meningitis.
• Canine juvenile polyarteritis syndrome.
• Corticosteroid-responsive meningomyelitis.
drug.
Biedermann E, Tipold A, Flegel T. Relapses in 
dogs with steroid-responsive meningitis-
arteritis. J Small Anim Pract 2016, 
57:91–95.

Canine and Feline, Seventh Edition  1295
SStertor and Stridor
  BASICS
• Abnormally loud sounds that result from 
air passing through a narrowed nasopharynx, 
pharynx, larynx, or trachea.
• Discontinuous sounds heard without a 
stethoscope.
• Stertor—low-pitched snoring sound that 
usually arises from the vibration of flaccid 
tissue or fluid; usually arises from nasal or 
pharyngeal airway obstruction.
• Stridor—higher pitched sounds that result 
when relatively rigid tissues are vibrated by 
the passage of air; result of partial or complete 
obstruction of the larynx or cervical trachea.
• Airway obstruction causes turbulence as air 
travels through a narrowed passage; with 
worsening obstruction or increasing airflow 
velocity, the amplification of airway sounds 
occur due to increased turbulence and 
vibration of tissue, secretions, or foreign 
bodies.
• Obstruction sufficient to increase the work 
of breathing augments respiratory muscle 
effort and exacerbates turbulence; 
inflammation and edema of tissues in the 
region of the obstruction may develop, 
further reducing the airway lumen and 
further increasing the work of breathing, 
creating a vicious cycle.
• Complete airway obstruction will result in 
the lack of sounds.
• Obesity further increases respiratory effort 
and exacerbates airway obstruction.
GENETICS
• Brachycephalic obstructive airway 
syndrome is heritable in many breeds, 
including English and French bulldogs, pugs, 
Boston terriers, shih tzus, and other 
• Congenital laryngeal paralysis has been 
identified in bouvier des Flandres, bull 
terriers, Siberian huskies, Alaskan Malamutes, 
and white-coated German shepherd dogs. 
Dalmatians, Rottweilers, Leonbergers, and 
Pyrenees mountain dogs.
• Older large breed dogs (e.g., Labrador 
retrievers) commonly develop laryngeal 
paralysis as part of a geriatric-onset laryngeal 
paralysis polyneuropathy complex.
Common
Worldwide
Species
Dog more than cat.Breed Predilections
• Common in brachycephalic dogs and less 
so cats
• Acquired laryngeal paralysis—overrepre-
sented in certain giant breeds (e.g., Saint 
Bernard and Newfoundlands) and large 
breeds (e.g., Irish setters, Labrador retrievers, 
and golden retrievers).
• Cats of any breed due to nasopharyngeal 
polyps, inflammatory or neoplastic laryngeal 
diseases, or laryngeal paralysis (the latter far 
less common in cats than dogs).
• Affected brachycephalic animals and dogs 
or cats with inherited laryngeal paralysis are 
typically younger than 1 year of age when 
owners detect a problem.
• Acquired laryngeal paralysis typically occurs 
in older dogs and cats.
No sex predilection for any cause, although 
inherited laryngeal paralysis has a 3:1 male 
predominance.
SIGNS
• Change or loss of voice.
• Partial obstruction—produces an increase 
in airway sounds before producing an obvious 
change in respiratory pattern or gas exchange.
• Owners may indicate that the sound has 
existed for as long as several years.
• Breath sounds audible from a distance without a 
stethoscope—suspect narrowing of upper airway.
• Nature of the sound—ranges from 
abnormally loud to obvious fluttering to 
high-pitched squeaking, depending on the 
degree of airway narrowing.
• Stress or exercise may amplify the sound or 
induce respiratory distress.
• May note increased respiratory effort and 
paradoxical respiratory movements (chest wall 
collapses inward during inspiration and 
springs outward during expiration) when the 
effort is extreme; respiratory motions often 
accompanied by obvious postural changes 
(e.g., abducted forelimbs, extended head and 
neck, and open-mouth breathing).
CAUSES
• Brachycephalic airway syndrome (stenotic 
nares, elongated soft palate, everted laryngeal 
saccules, laryngeal collapse).
• Laryngeal paralysis—inherited or acquired.
• Laryngeal neoplasia—benign or malignant.
• Granulomatous/inflammatory laryngitis.
• T racheal collapse, stenosis, obstruction, 
• Nasopharyngeal polyp, stenosis, foreign body.
• Cervical bite wounds.
• Neuromuscular dysfunction.
• Anesthesia or sedation—only if 
predisposing anatomy exists.
• Cleft palate.
• Aplasia of soft palate.
• Redundant pharyngeal mucosal folds.
• Soft palate mass.• Edema or inflammation of the palate, pharynx, 
and larynx (including everted mucosal lining of 
the laryngeal ventricles)—secondary to coughing, 
vomiting or regurgitation, turbulent airflow, 
upper respiratory infection, and hemorrhage.
• Secretions (e.g., pus, mucus, and blood) in 
the airway lumen.
• High ambient temperature or humidity.
• Fever.
• High metabolic rate—as occurs with 
hyperthyroidism or sepsis.
• Exercise.
• Anxiety or excitement.
• Any respiratory or cardiovascular disease 
that increases ventilation.
• T urbulence caused by the increased airflow 
can lead to swelling and worsen the airway 
• Hypothyroidism or polyneuropathy.
• Obesity.
  DIAGNOSIS
• Systematically auscultate over the nose, 
pharynx, larynx, and trachea to identify the 
point of maximal intensity of any abnormal 
sound and to identify the phase of respiration 
when it is most obvious.
• Important to identify the anatomic location 
from which the abnormal sound arises and to 
seek exacerbating causes (see Risk Factors; 
e.g., a chronic airway obstruction may 
become manifest when the patient is exposed 
to extremely high ambient temperatures).
• Must differentiate sounds of pharyngeal, 
laryngeal, and tracheal narrowing from sounds 
arising elsewhere in the respiratory system.
• Nasal and tracheal narrowing and severe or 
extensive narrowing of the bronchi—can 
cause increased respiratory sounds.
• If the sound persists when the patient 
opens its mouth, a nasal cause can virtually 
be ruled out.
• If the owner describes a change in voice, the 
larynx is the likely abnormal site.
Arterial blood gases—help characterize the 
degree of respiratory compromise (e.g., degree 
of hypoxemia, hypercapnia, or acid–base 
disturbances).
IMAGING
• Lateral radiographs of the head and 
neck—may help identify abnormal soft tissues 
of the airway (e.g., elongated soft palate or a 
nasal polyp); limited use for identifying 
laryngeal paralysis, although experienced 
radiographers can identify abnormally dilated 
or swollen laryngeal saccules; cartilaginous 
destruction is suggestive of neoplasia or 
granulomatous laryngitis; may detect external 
masses compressing the upper airway.

1296  Blackwell’s Five-Minute Veterinary Consult  
S• Radiography and fluoroscopy—important 
for assessing the cardiorespiratory system; rule 
out other or additional causes of respiratory 
difficulty; such conditions may add to an 
underlying upper airway obstruction, causing 
a subclinical condition to become clinical.
• Ultrasound can be used to assess laryngeal 
structure and function, can also be used to 
document cervical tracheal collapse but air is 
a poor acoustic window.
• CT can be used to provide additional 
anatomic detail.
• Definitive diagnostic tests for direct visuali -
zation of pharyngeal or laryngeal changes.
• Requires sedation that preserves laryngeal 
function. Recommend propofol 4–8 mg/kg 
IV to effect.
• The patient’s ability to use muscles to open 
the airway is compromised by anesthesia; be 
prepared to correct any lesions found, at a 
minimum, be prepared to intubate.
• If correctable conditions are not identified and 
corrected—patient’s recovery from anesthesia can 
be complicated by severe airway obstruction; 
must be prepared to perform a tracheotomy if 
airway is obstructed and a definitive surgical 
remedy cannot be pursued immediately.
• Assess timing and degree of movement of the 
arytenoids during light anesthesia—laryngeal 
paralysis results in lack of abduction of the 
arytenoids during inspiration. Use doxapram 
1–2 mg/kg IV to stimulate respiration if needed.
• Normal palate—thin; just barely overlaps 
the tips of the epiglottis; easily displaced 
dorsally using the blade of the laryngoscope.
• Overlong soft palate—thick; usually inflamed; 
may lie 1 cm or more past the tip of the epiglottis.
  TREATMENT
• Inpatient management required for surgical 
• Closely monitor effects of sedatives; 
sedatives can relax the upper airway muscles 
and worsen the obstruction; be prepared with 
emergency methods for securing the airway if 
complete obstruction occurs.
• In cases of suspected laryngeal paralysis resulting 
in respiratory distress and partial obstruction in 
dogs, sedation with butorphanol 0.2–0.3 mg/kg 
and acepromazine 0.025–0.05 mg/kg with 
oxygen supplementation and active cooling 
measures if hyperthermic may be indicated.
• If available, use of high-flow oxygen nasal 
cannulation has been successful to treat 
partial airway obstruction.
• Severe or complete airway obstruction—
attempt an emergency intubation; if 
obstruction prevents intubation, emergency 
tracheostomy or passage of a tracheal catheter 
to administer oxygen may be the only available means for sustaining life; a tracheal 
catheter can briefly sustain oxygenation while 
a more permanent solution is sought.
• T reatment requires removal of obstruction, 
supplemental oxygen is variably helpful.
• IV fluids may be required, particularly if 
hyperthermia develops from increased work 
of breathing.
• Active cooling measures (ice packs in axilla 
and groin region, alcohol on foot pads, 
chilled IV fluids) helpful in alleviating 
hyperthermia but not indicated for fever.
ACTIVITY
Keep patient cool, quiet, and calm—anxiety, 
exertion, and pain lead to increased ventila-
tion, potentially worsening the obstruction.
DIET
• NPO if anesthesia is planned.
• Dietary management to avoid obesity, a 
known risk factor for developing airway 
obstruction and associated stertor or stridor.
Inform client that the patient can make the 
transition from being a noisy breather to 
having an obstructed airway in a few minutes 
or even seconds.
• Laryngoscopy and bronchoscopy for foreign 
body retrieval and biopsy of laryngeal region and 
tracheal lumen. Use of small balloon catheters 
passed beyond the foreign body prior to expansion 
may be useful in removing some objects.
• Take particular care when inducing general 
anesthesia or when using sedatives in any 
patient with upper airway obstruction.
• Surgery—indicated to obtain a diagnosis 
through biopsy with histopathology, to manage 
obstruction while awaiting histopathology 
results or resolution of inflammation/infection 
(e.g., tracheotomy), or to resolve disease by 
excision, correction of obstructive lesion, and 
removal of foreign bodies.
• Medical approaches—appropriate only if 
the underlying cause is infection, edema, 
inflammation, or hemorrhage; anatomic or 
neurologic causes are not amenable to 
• Steroids—may be indicated if edema or 
inflammation is thought to be an important 
contributor; effect with IV administration of a 
short-acting glucocorticoid such as dexametha -
sone sodium phosphate (1 mg/kg prednisone 
equivalent) should be apparent in the first 
several hours. Single dose may be sufficient, or a 
tapering dose might be required. Inflammatory 
laryngitis often requires higher doses adminis -
tered over a longer dosing schedule with taper of 
the dose according to resolution of clinical signs.PRECAUTIONS
Sedatives, analgesics, and anesthetics—avoid 
excessive suppression of laryngeal movement 
and respiratory suppression to avoid 
aspiration in animals with laryngeal disease.
  FOLLOW-UP
Respiratory rate and effort need to be closely 
monitored. When owner chooses to take an 
apparently stable patient home, or if continual 
observation is not feasible, inform client that 
complete obstruction could occur.
Advise client to avoid exercise, high ambient 
temperatures, and extreme excitement.
Serious complications may occur without 
therapy to relieve the obstruction; these 
include airway edema, pulmonary edema 
(may progress to life-threatening acute lung 
injury), and hypoventilation; may require 
tracheotomy and/or artificial ventilation.
• Even with surgical treatment, some degree 
of obstruction may remain for 7–10 days due 
to swelling.
Peripheral neuropathy often associated with 
SYNONYMS
Snoring
SEE ALSO
MacPhail C. Laryngeal disease in dogs and 
cats. Vet Clin Small Anim 2014, 44:19–31.
Sumner C, Rozanski EA. Management of 
respiratory emergencies in small animals. 
Vet Clin Small Anim 2013, 43:799–815.
C. Preuter.
available onlineStertor and Stridor  (continued)

Canine and Feline, Seventh Edition  1297
SStomatitis and Oral Ulceration
  BASICS
• Stomatitis—an inflammation of the tissues 
of the oral cavity, more specifically defined 
below.
• Ulceration—focal or multifocal loss of 
mucosal integrity of the superficial epithelial 
layers in specific areas of the oral cavity.
Nomenclature—oral and oropharyngeal 
inflammation is classified by location as:
in clinical use the term should be reserved to 
describe widespread oral inflammation 
(beyond gingivitis and periodontitis) that may 
also extend into submucosal tissues (e.g., 
marked caudal mucositis extending into 
submucosal tissues may be termed caudal 
stomatitis).
◦ Gingivitis—inflammation of gingiva.
◦ Periodontitis—inflammation of 
nongingival periodontal tissue (i.e., the 
periodontal ligament and alveolar bone).
◦ Alveolar mucositis—inflammation of 
alveolar mucosa.
◦ Sublingual mucositis—inflammation of 
mucosa on the floor of the mouth.
◦ Labial/buccal mucositis—inflammation 
of the lip/cheek mucosa.
mucosa of the caudal oral cavity.
◦ Contact mucositis and contact mucosal 
ulceration (“contact ulcers” and “kissing 
ulcers”)—lesions in susceptible individuals 
that are secondary to mucosal contact with 
a tooth surface bearing the responsible 
irritant, allergen or antigen.
◦ Palatitis—inflammation of mucosa 
covering the hard and/or soft palate.
◦ Glossitis—inflammation of mucosa 
of the dorsal and/or ventral tongue surface.
◦ Cheilitis—inflammation of the lip 
(including the mucocutaneous junction 
area and skin of the lip).
◦ Osteomyelitis—inflammation of the 
bone and bone marrow.
◦ Tonsilitis—inflammation of the palatine 
tonsil(s).
◦ Pharyngitis—inflammation of the pharynx.
• Metabolic:
◦ Diabetes mellitus.
◦ Hypothyroidism.
◦ Renal disease—uremia.
• Nutritional:
◦ Protein-calorie malnutrition.
◦ Riboflavin deficiency.
• Neoplastic:
◦ Dog—malignant melanoma; squamous 
cell carcinoma; fibrosarcoma.◦ Cat—squamous cell carcinoma; 
fibrosarcoma; malignant melanoma.
• Immune-mediated:
◦ Pemphigus vulgaris—90% have oral 
◦ Bullous pemphigoid—80% have oral 
◦ Systemic lupus erythematosus—50% 
have oral involvement.
◦ Discoid lupus erythematosus.
• Drug-induced—toxic epidermal necrolysis, 
erythema multiforme.
• Infectious:
◦ Retrovirus—feline leukemia virus/feline 
immunodeficiency virus (FeLV/FIV).
◦ Calicivirus—cat.
◦ Herpesvirus—cat.
◦ Leptospirosis—dog.
◦ Periodontal disease—dog and cat.
• T raumatic:
◦ Foreign body—bone or wood 
fragments.
◦ Electric cord shock.
◦ Malocclusion.
◦ Gum-chewer’s disease—chronic chewing 
of cheek or sublingual mucosa.
• Chemical/toxic:
◦ Acids—etching gels for dental procedures 
(37% phosphoric acid).
◦ Bases: hypochlorite, cleaning solutions.
◦ Thallium.
• Idiopathic:
◦ Eosinophilic granuloma—cats, Siberian 
huskies, Samoyeds.
◦ Feline stomatitis—cats; feline chronic 
gingivostomatitis (FCGS).
◦ Canine ulcerative stomatitis—dogs; 
allergic, hypersensitivity reaction to plaque.
◦ Idiopathic osteomyelitis—dogs.
Gastrointestinal (oral).
Variable
Species
Dogs and cats of any age and either sex.
• Breed predilection for canine ulcerative 
stomatitis (aka chronic ulcerative paradental 
stomatitis [CUPS])—Maltese, cavalier King 
Charles spaniels, cocker spaniels, bouvier des 
Flandres.
• Feline stomatitis—FCGS may have 
predilection for Somali and Abyssinian cats.
• Idiopathic osteomyelitis—may have 
predilection for cocker spaniels; complication 
associated with canine ulcerative stomatitis.
Any age.
Either gender.SIGNS
• History and oral examination—foreign 
bodies; malocclusions; chemical, toxic, and 
electrical burns.
• Idiopathic conditions—clinical signs; history; 
breed predispositions; response to therapy.
• Behavior changes secondary to oral sensitivity.
• Note: In canine ulcerative stomatitis, 
occasionally these signs will start following a 
routine dental cleaning on a previously 
“normal” patient; probably would have 
occurred eventually, just exacerbated by 
manipulation in the oral cavity.
• Pharyngitis.
• Buccitis/buccal mucosal ulceration.
• Hypersalivation (thick, ropey saliva).
• Pain.
• Contact mucosal ulceration or contact 
mucositis—“kissing ulcers” common in 
canine ulcerative stomatitis.
• Plaque—with or without calculus.
• Exposed, necrotic bone—with alveolar 
osteitis and idiopathic osteomyelitis.
• Scar formation on lateral margins of 
tongue—with canine ulcerative stomatitis.
  DIAGNOSIS
• CBC, biochemistry, urinalysis, and 
thyroxine (T4)—diabetes mellitus, renal 
disease, hypothyroidism, infections, and for 
preoperative considerations.
• Chronic conditions may have elevated 
serum total protein and elevated globulin 
levels due to chronic antigen stimulation; 
T4 may be decreased secondarily.
• Serology—FeLV/FIV test; titers for specific 
• Cultures—usually nonspecific; oral flora 
contaminants.
IMAGING
Radiography—helps determine bony 
involvement, and other conditions such as 
periodontal disease or tooth resorption, and 
extent of idiopathic osteomyelitis.
Biopsy/cytology—neoplasia, immune-mediated 
disease, and chronic inflammation result in 
predominant lymphocytes and plasmocytes (in 
canine ulcerative stomatitis and feline stomatitis).
See definitions above.

1298  Blackwell’s Five-Minute Veterinary Consult  
S  TREATMENT
Underlying metabolic or other disease—treat 
systemic illness appropriately.
Supportive therapy—soft diet; fluids; 
hospitalization in severe cases.
DIET
• Nutritional support—via pharyngostomy 
or esophagostomy feeding tube.
• May consider hypoallergenic diet.
• Canine ulcerative stomatitis—continuous, 
meticulous home care to prevent plaque 
accumulation; dental cleaning initially and 
frequently; periodontal therapy; extraction of 
diseased teeth.
• Warn client that prognosis is guarded, 
response to therapy depends on underlying 
cause, and prolonged treatment and/or 
further extractions may be necessary.
• In canine ulcerative stomatitis or feline 
stomatitis, any level of home care that can be 
provided is encouraged (brushing or topical 
• Select extractions (partial, caudal, or full 
mouth)—may be indicated for chronic 
idiopathic conditions (e.g., canine ulcerative 
stomatitis and feline stomatitis) to remove the 
source of reaction (plaque/teeth).
• Removal of entire tooth structure is important.
• Removal of necrotic/avascular bone, 
gingival flap closure, and broad-spectrum 
antibiotics—indicated for idiopathic 
osteomyelitis; monitor for recurrence.
• Antimicrobials—treat primary and secondary 
bacterial infections; may be used intermittently 
between cleanings for therapeutic assistance, 
but the owner must be cautioned that chronic 
use could lead to antibiotic resistance; 
clindamycin 11 mg/kg PO q12h; amoxicillin–
clavulanate 12.5–25 mg/kg PO q12h; 
tetracycline 10–22 mg/kg PO q8h.• Anti-inflammatory/immunosuppressive 
drugs—the comfort of the patient must be 
weighed against potential long-term side 
effects of corticosteroid usage; prednisone 
0.5–1.0 mg/kg q12–24h PO, taper dosage:
◦ For eosinophilic granuloma—prednisolone 
2–4.4 mg/kg PO once a day; for chronic 
cases use 0.5–1.0 mg/kg PO every other day.
◦ Cyclosporine 5 mg/kg PO q24h. 
Therapeutic serum levels after 6 weeks if no 
• Mucosal protectants—for chemical insults; 
sucralfate 1 g/25 kg q8h PO; cimetidine 5–10 
mg/kg q8–12h PO.
• Analgesics—carprofen 0.5 mg/kg PO 
q12–24h; hydrocodone 0.22 mg/kg q8–12h; 
tramadol 2.2–4.4 mg/kg PO q6–12h; 
gabapentin 5–10 mg/kg PO SID.
• Topical therapy—chlorhexidine solution or 
gel (antibacterial); zinc gluconate/ascorbic 
acid; stabilized chlorine dioxide for halitosis.
Corticosteroids are contraindicated in 
patients with systemic fungal infections.
• Some antimicrobials may upset the 
• Avoid corticosteroids in patients that may 
already be immunocompromised (i.e., those 
with FeLV or FIV).
• Do not use these medications in patients 
with known hypersensitivities.
  FOLLOW-UP
Optimal home care and regular professional 
cleaning and treatment is essential.
Idiopathic osteomyelitis may occur in some 
canine ulcerative stomatitis patients (see above).ZOONOTIC POTENTIAL
N/A, unless immunocompromised 
SYNONYMS
• Chronic ulcerative paradental stomatitis 
(CUPS).
• Ulcerative stomatitis.
• Gingivostomatitis.
• Vincent’s stomatitis.
• Necrotizing stomatitis.
SEE ALSO
Feline Stomatitis—Feline Chronic 
Gingivosomatitis (FCGS).
• CUPS = chronic ulcerative paradental 
stomatitis.
• FCGS = Feline chronic gingivostomatitis.
Harvey CE. Veterinary Dentistry. 
Philadelphia, PA: Saunders, 1985.
Lobprise HB, Wiggs RB. The Veterinarian’s 
Companion for Common Dental 
Procedures. Lakewood, CO: AAHA Press, 
2000.
Manfra Maretta S, Brine E, Smith CW, et al. 
Idiopathic mandibular and maxillary 
osteomyelitis and bone sequestra in cocker 
spaniels. In: Proceedings of the Veterinary 
Dental Forum, Denver, CO, 1997; 
sponsored by the American Veterinary 
Dental College, Academy of Veterinary 
Dentistry, and the American Veterinary 
Dental Society.
Smith MM. Oral and salivary gland 
disorders. In: Ettinger SJ, ed., Textbook 
of Veterinary Internal Medicine, 5th ed. 
Philadelphia, PA: Saunders, 2000, 
pp. 1114–1121.
Dentistry Principles & Practice. 
Author  R. Michael Peak
Consulting Editor  Heidi B. LobpriseStomatitis and Oral Ulceration  (continued)

Canine and Feline, Seventh Edition  1299
SStreptococcal Infections
  BASICS
OVERVIEW
• Streptococcus —Gram-positive, nonmotile, 
facultatively anaerobic spherical bacteria (cocci):
⚬ Commensal organisms; normal flora of 
the upper respiratory tract, oropharynx, 
lower genital tract, and skin.
⚬ Under appropriate conditions, capable of 
infecting all areas of body; frequent 
secondary invader of body tissues.
• Classified by ability to hemolyze red blood 
cells on blood agar plates:
⚬ α-Hemolytic (green zone of partial 
hemolysis).
⚬ β-Hemolytic (clear zone of hemolysis); usually 
more pathogenic than α-hemolytic, which is 
more pathogenic than nonhemolytic strains.
⚬ γ-Hemolytic (no change; nonhemolytic).
• Hemolytic strains further subdivided by 
differences in cell walls (Lancefield serogroups 
A–H and K–T); some groups more likely to 
be associated with disease:
⚬ Group G is associated with cats and dogs; 
group A with humans).
⚬ Many group D streptococci reclassified as 
enterococci.
• Produce exotoxins—streptolysins (hemo-
lysins), streptokinases, deoxyribonucleases, 
and hyaluronidases.
• Adhesins to bind extracellular matrix 
proteins.
• Very young—more prone to infection 
because of incomplete immunity; particularly 
kittens born to primiparous queen.
SIGNS
• Vary with site of infection and host 
immunocompetence. Sites of infection can 
include abscesses, genitourinary tract, ears, 
septicemia (e.g., toxic shock syndrome), 
joints, lungs, heart valves, lymph nodes, 
CNS, wounds (e.g., necrotizing fasciitis), 
tonsil/pharynx, or skin, and may result in 
abortion, fading puppies/kittens, or bitch/
queen sterility.
• Dyspnea.
• Fever.
• Pain.
• Age, exposure, and immune response 
determine disease severity.
• Virulence—depends on specific organism.
• Opportunistic—surgical or traumatic 
wounds, viral infections, atopic dermatitis, 
immunosuppressive conditions.• Coinfection with canine influenza virus 
increases disease severity. Other predisposing 
conditions—feline leukemia virus, feline 
infectious peritonitis, immunodeficiency, 
respiratory viral infections, feline lower 
• Maternal antibodies generally protect 
neonates.
• Carrier state occurs.
• Bacterial superantigens may contribute to 
toxic shock syndrome and necrotizing 
fasciitis; enrofloxacin-induced bacteriophages 
may enhance superantigen expression.
  DIAGNOSIS
Other infectious causes—viruses, bacteria, 
fungi, Rickettsia,  protozoa.
• Normal or high leukocytes with neutrophilia 
and left shift or degenerative left shift.
• Cocci—in circulating neutrophils if 
overwhelming sepsis.
• Biochemistry—suggests predisposing 
• Urinalysis—pyuria (with or without 
• Gram stain—of exudates; Gram-positive 
cocci in chains or singlets.
• Culture and susceptibility testing —affected 
tissues, exudate or needle aspirates.
• PCR.
IMAGING
Radiographs—interstitial or alveolar 
pulmonary pattern (pneumonia); radiodense 
uroliths (struvite).
• Acute inflammation—gross or microscopic 
abscesses.
• Septicemia—omphalophlebitis, peritonitis, 
hepatitis, pneumonia, myocarditis.
  TREATMENT
• Good nursing care.
• Rehydrate.
• Drain and flush abscess.
• Debride necrotic tissue.
• Ampicillin 22–30 mg/kg IV, IM, SC, PO 
q8h; combined with aminoglycoside 
(gentamicin or amikacin) for group B.• Amoxicillin 22 mg/kg PO q8–12h.
• Amoxicillin–clavulanate 22 mg/kg PO 
q12h.
• Penicillin—penicillin G 10,000–20,000 U/
kg IM, SC q12–24h or penicillin V 8–30 mg/
kg PO q8h.
• Erythromycin 10–20 mg/kg IV, SC, PO 
q8h.
• Clindamycin 10–15 mg/kg PO, IV, SC 
q12h.
• Avoid immunosuppressive drugs; aminogly-
cosides contraindicated with renal disease.
• Enrofloxacin—contraindicated for 
necrotizing fasciitis.
  FOLLOW-UP
• Avoid overcrowding, maintain clean 
feeders and environment, segregate infected 
animals.
• Newborns—dip navel and umbilical cord in 
2% tincture of iodine, consider prophylactic 
antibiotic treatment of kittens born to 
primiparous queens.
• Animals may show no clinical signs with 
group A streptococci but may serve as 
reservoir for human infection.
• Streptococci isolated from people are 
usually of human, not animal, origin.
• S. canis  infections in people reported 
from dog bites and wounds in contact with 
dogs.
Antimicrobial use guidelines for treat -
ment of respiratory tract disease in dogs 
and cats. J Vet Intern Med 2017, 
31:279–294.
Little SE. Emerging aspects of streptococcal 
infections in cats. In: Little SE, ed., August’s 
64–72.
Sykes JE. Streptococcal and enterococcal 
infections. In: Sykes JE, ed., Canine and 
Elsevier, 2014, pp. 334–346.

1300  Blackwell’s Five-Minute Veterinary Consult  
SStupor and Coma
  BASICS
• Stupor—unconscious but arousable with 
noxious stimuli. • Coma—unconscious, not 
arousable with noxious stimuli.
Any severe pathologic change (anatomic or 
metabolic) of the ascending reticular 
activating system (network of neurons 
situated in the core of the brainstem) and/or 
arousal system for the cerebral cortex can lead 
to depression, stupor, or coma.
• Nervous. • Cardiovascular. • Neuromuscular. 
• Ophthalmic. • Respiratory.
• Dog and cat. • No breed, age, or sex 
SIGNS
• Possibility of trauma or unsupervised 
roaming. • Past medical problems of 
significance—diabetes mellitus, insulin therapy; 
hypoglycemia; cardiovascular problems; hypoxic 
episodes; renal failure; liver failure; neoplasia. 
• Patient’s environment—possible heatstroke; 
hypothermia; drowning; exposure to drugs, 
including owner’s medications, narcotics, toxins 
(e.g., ethylene glycol, lead, anticoagulants). 
• Onset may be acute or slowly progressive, 
• Evidence of external or internal trauma. 
• Severe hypo- or hyperthermia. • Evidence 
of hypoxia or cyanosis, ecchymosis or 
petechiation, cardiac or respiratory 
insufficiency—warrants investigation for 
metabolic causes. • Palpate for evidence of 
neoplasia. • Retinal hemorrhages or distended 
vessels—hypertension. • Papilledema—
cerebral edema. • Retinal detachment—
infectious, neoplastic, or hypertensive causes. 
• Chorioretinitis—infectious causes (distemper, 
feline leukemia virus [FeLV]-related diseases, 
toxoplasmosis, cryptococcosis, or coronavirus). 
• Sustained bradycardia (with normal serum 
potassium)—midbrain, pontine, or medullary 
lesion.
• Differentiate cerebrum–diencephalic lesion 
from brainstem lesion (better vs. worse 
prognosis). • Determine level of consciousness 
and if patient arousable. • Pupillary light 
reflexes—small responsive pupils: cerebral or 
diencephalic lesion; dilated unresponsive 
pupils (unilateral or bilateral) or fixed in 
midposition: midbrain or severe medullary 
lesions. • Oculocephalic reflex (when cervical 
manipulation possible)—loss of physiologic vestibular nystagmus: brainstem involvement. 
• Respiratory patterns—Cheyne-Stokes 
respiration: severe, diffuse cerebral or 
diencephalic lesion; hyperventilation: 
midbrain lesion; ataxic or apneustic breathing: 
pons or medulla lesion. • Cranial nerve 
(CN)—deficits with lesion of cerebrum–
diencephalon: CN I, II; deficits of CN III: 
midbrain lesion; deficits of CN V–XII: pons 
and medulla lesions. • Postural changes—
decerebrate rigidity: midbrain lesion.
CAUSES
• Drugs—narcotics, anesthetics, depressants, 
ivermectin. • Anatomic—hydrocephalus. 
• Metabolic—severe hypoglycemia, hyper -
glycemia, hyperosmolar syndromes, 
hypernatremia, hyponatremia, hepatic 
encephalopathy, hypoxemia, hypercarbia, 
hypothermia, hyperthermia, hypotension, 
coagulopathies, renal failure, lysosomal storage 
disease, severe hypothyroidism. 
• Nutritional—hypoglycemia, thiamine 
deficiency. • Neoplastic (primary)—
meningioma, astrocytoma, gliomas, choroid 
plexus papilloma, pituitary adenoma, others.  
• Metastatic—hemangiosarcoma, lymphoma, 
mammary carcinoma, others. • Inflammatory 
noninfectious—granulomatous meningo -
encephalomyelitis. • Infectious—bacterial, 
viral (distemper, feline coronavirus [FCoV]), 
parasitic (aberrant larva migrants), protozoal 
(neosporosis, toxoplasmosis), fungal 
(cryptococcosis, blastomycosis, histoplasmosis, 
coccidioidomycosis, actinomycosis), tick-
borne diseases. • Idiopathic—epilepsy (post 
status epilepticus). • Immune-mediated—
brain edema, vasculitis and thrombocytopenia 
leading to hemorrhage.  • T rauma—most 
common cause. • Toxins—ethylene glycol, 
lead, rodenticides, others. • Vascular—
hemorrhage (bleeding disorders, hypertension), 
infarction (feline ischemic encephalopathy, 
hypercoagulable disease, microfilaria, or 
migrating adult heartworm).
• Diabetes mellitus—insulin therapy. 
• Hepatic failure. • Insulinoma. • Severe heat 
or cold exposure without protection. 
• Free-roaming animals—trauma. • Young 
and unvaccinated animals. • Hypertension.
  DIAGNOSIS
• Acute onset—most commonly caused by 
toxins, drugs, trauma, or vascular accidents.  
• Slow progression of neurologic signs 
without systemic abnormalities—suggests 
primary neurologic disorders of inflammatory, 
neoplastic, or anatomic causes. • Bilateral 
diffuse cortical signs—metabolic diseases, 
toxins, systemic infection, drugs, and nutritional causes. • Brainstem signs—
trauma, inflammation, neoplasia, vascular 
accidents, or progression of cerebral disease 
causing tentorial herniation.
CBC
• Lead toxicity—may show nucleated red 
blood cells or basophilic stippling. • Severe 
infection—inflammatory hemogram. 
• Severe anemia—suggests hypoxemia.
May see hypoglycemia, hyperglycemia, 
hypernatremia, azotemia, hyperosmolarity, 
and other metabolic derangements.
• Diabetes mellitus—glycosuria. • Renal 
failure—isosthenuria, granular casts. 
• Immune-mediated disease or severe 
infection—proteinuria. • Hepatic 
encephalopathy—ammonium biurate 
crystals.  • Ethylene glycol toxicity—calcium 
oxalate or hippurate crystals.
• Serum ethylene glycol level and osmolar 
gap—acute onset. • Serum ammonia 
concentration and preprandial and 
postprandial bile acids—high levels indicate 
hepatic encephalopathy. • Serum and CSF 
titers—suspected infectious disease. • Arterial 
blood gases—evidence of hypoxemia; severe 
pH changes; hypo- and hypercarbia.  
• Coagulogram—including prothrombin 
time (PT), partial thromboplastin time 
(PTT), fibrinogen, fibrin degradation 
product, D-dimer, platelet count, anti -
thrombin, buccal bleeding time, thrombo -
elastography; suspected intracranial bleeding 
or thrombosis. • Serologic testing—FeLV, 
feline immunodeficiency virus (FIV), FCoV, 
protozoal and heartworm disease. • Serum 
toxicity levels (e.g., lead, macrolide, other 
toxins). • Thyroid panel.
IMAGING
• Survey radiographs (thorax and abdomen)—
evidence of heavy metal, organ enlargement, 
infiltration, or neoplasia. • Skull radiographs—  
fractures in trauma cases, lytic lesions, masses. 
• CT—excellent for detecting acute 
hemorrhage within calvaria; depressed 
fractures; lytic lesions, penetrating foreign 
bodies. • MRI with contrast—demonstrates 
cerebral edema, hemorrhage, mass, infiltrative 
diseases, vascular interruption.
• CSF—cytology, protein and 
immunoglobulin concentrations, and titers 
for infectious diseases; perform only when no 
evidence of trauma, increased intracranial 
pressure, coagulopathies, or metabolic disease. 
• Brainstem auditory-evoked response—
determine brainstem function. • ECG, 
echocardiogram—determine cardiac

Canine and Feline, Seventh Edition  1301
Sdysfunction; abnormalities may contribute to 
stupor or coma or may be caused by brain 
disease. • EEG—detect nonclinical seizure 
activity that can prolong stupor and coma.
Cerebral edema, hemorrhage, infarct, 
ischemia, inflammation, neoplasia, herniation, 
laceration, contusion, hematomas, skull 
fracture, necrosis, and apoptosis.
  TREATMENT
Poor Perfusion
• Small-volume fluid resuscitation technique; 
a combination of hydroxyethyl starch with 
balanced isotonic crystalloids. • Use peripheral 
veins, leaving the jugular vein blood flow 
unobstructed; shifting blood volume into the 
jugular veins is an important compensatory 
mechanism during high intracranial pressure 
(ICP). • Maintain systolic BP >90 mmHg; 
avoid hypertension. • Hydration—maintain 
with a balanced electrolyte crystalloid solution. 
• The head and neck should be leveled with 
the body or elevated to a 20° angle. • Oxygen 
supplementation—avoid a cough or sneeze 
reflex during intubation or nasal cannula 
placement; administer lidocaine (dogs, topical 
and/or 1–2 mg/kg IV) before intubation to 
blunt the gag and cough reflex. • Pao2 must be 
>50 mmHg to maintain cerebral blood flow 
autoregulation in normal brain tissue.
Ventilation
• Protect airway with intubation. • Paco2—
maintain between 35 and 45 mmHg.
Reduce Increase In ICP
• Prevent thrashing, seizures, or any other 
form of uncontrolled motor activity that can 
elevate ICP; diazepam infusion 0.5–1 mg/
kg/h, midazolam 0.2–0.4 mg/kg, or propofol 
3–6 mg/kg IV titrated to effect; then 0.1–0.6 
mg/kg/min CRI; levetiracetam 20 mg/kg IV/
IM/rectal q8h if seizure activity. • Ensure 
systolic BP >90 mmHg. • 7% hypertonic 
saline (2–4 mL/kg IV); can reduce fluid 
volume needed to reach resuscitation 
endpoints; can combine with colloid. 
• Furosemide 0.75 mg/kg IV; may decrease 
CSF production. • Mannitol 0.5–1 g/kg IV 
bolus repeated at 2-hour intervals 3 or 4 times 
in dogs, and 2 or 3 times in cats; repeated 
doses must be given on time; improves brain 
blood flow and lowers ICP . • Hyperventilation 
(Paco2 32–35 mmHg) for 48 hours using 
mechanical ventilation; requires intensive 
monitoring. • Ventriculostomy for CSF 
drainage if critical elevation of ICP 
nonresponsive to medical treatment. 
• Consider surgical decompression and 
exploration—if cerebral dysfunction is progressing to midbrain signs with a history of 
trauma or bleeding (tentorial herniation); high 
ICP not responsive to medical therapy (if 
monitoring instrumentation available); 
depressed skull fracture fragments; penetrating 
foreign body; requires intensive monitoring.
• Prevent secondary complications of 
recumbency—eye lubrication; aseptic 
technique with catheters; turning; rehabil -
itation exercises. • Prevent urine/fecal 
scalding. • Careful nasogastric tube feeding 
for early trickle flow feeding; cisapride 
0.5 mg/kg PO q8–12h and metoclopramide 
1–2 mg/kg/day may promote gastrointestinal 
motility.
Underlying Disease
• Glucocorticosteroids—inflammatory, 
immune-mediated and space-occupying 
intracranial abnormalities. • Lactulose enemas, 
flumazenil 0.02 mg/kg IV and fluid support—
hepatic encephalopathy. • Fluid diuresis, 
dialysis—renal failure. • Rehydration and 
insulin—diabetes mellitus with hyperosmolal -
ity; lower glucose slowly. • Glucose supple -
mentation—hypoglycemia. • Support IV 
volume; cool—hyperthermia. • Support IV 
volume; warm to ≥98°F/36.5°C—hypothermia. 
• Gastric lavage and instillation of activated 
charcoal with a cathartic. • Dialysis—   
low-molecular-weight toxins. • Antibiotics—
use agents that cross the blood–brain barrier 
for suspected bacterial infections (e.g., 
trimethoprim-sulfa, clindamycin, doxycy-
cline, metronidazole). • Adjust crystalloid 
fluid selection to correct electrolyte disorders. 
• Thiamine (cat, 5–50 mg; dog, 1–20 mg 
IV)—possible thiamine deficiency.
• Avoid hypo- and hypertension, hypo- and 
hyperglycemia. • Avoid IV volume overload. 
  FOLLOW-UP
• Serial neurologic examinations—detect 
deterioration that warrants aggressive 
therapeutic intervention. • BP—keep fluid 
therapy adequate for perfusion while avoiding 
hypertension. • Blood gases—assess need for 
oxygen supplementation or ventilation; 
monitor Pco2 when hyperventilating. • Blood 
glucose—ensure adequate level to maintain 
brain functions while avoiding hyperosmolality. 
• ECG—detect arrhythmias that may affect perfusion, oxygenation, and cerebral blood 
flow. • ICP—detect marked elevations; track 
success of therapeutics. • Electrolytes—detect 
hypernatremia and hypokalemia.
• Keep pets confined or leashed. • Prevent 
exposure to toxins or in-home medications. 
• Routine healthcare program to minimize 
infectious and metabolic disease 
• Short-term prognosis poor, other than 
related to hypoglycemia. • Pathology of 
brainstem worse than pathology of cerebral 
cortex. • Modified Glasgow Coma Score can 
provide prognostic information.
• Paco2 = partial pressure of carbon dioxide 
• Pao2 = partial pressure of arterial oxygen.
SEE ALSO
Brain Injury.
https://bvns.net/wp-content/
uploads/2016/09/Neurotransmitter-2.0-
MGCS-final.pdf
Chrisman CL, Mariani C, Platt S. Dementia, 
stupor and coma. In: Neurology for the 
Small Animal Practitioner. Jackson, WY: 
Teton NewMedia, 2003, pp. 41–84.
Parratt CA, Firth AM, Boag AK, et al. 
Retrospective characterization of coma and 
stupor in dogs and cats presenting to a 
multicenter out-of-hours service (2012–
2015): 386 animals. J Vet Emerg Crit Care 
2018, 28:559–565.
available online(continued)  Stupor and Coma

1302  Blackwell’s Five-Minute Veterinary Consult  
SSubarachnoid Cysts (Arachnoid Diverticulum)
  BASICS
Subarachnoid cysts refer to dilation of the 
subarachnoid space causing compression of 
the underlying brain or spinal cord. The use 
of the term “cyst” is misleading, as most do 
not have a defined cyst wall with an epithelial 
lining and the term subarachnoid diverticulum 
is frequently used when the lesion is spinal in 
location. This term is also problematic in 
cases in which arachnoid scarring simply 
causes dilation of the subarachnoid space.
• There are several proposed etiologies of 
subarachnoid cysts. • Any disease process that 
causes arachnoiditis has the potential to cause 
adhesions that result in the formation of 
one-way valves through which CSF flows, but 
cannot return, causing accumulation of CSF . 
• Congenital forms of the disease may result 
from abnormal splitting of the arachnoid 
membrane during development.
Nervous—spinal cord and brain 
(quadrigeminal cistern).
GENETICS
Certain breeds appear to be predisposed (e.g., 
pug, Rottweiler for spinal cord, Pekingese, 
shih tzu for brain). There are no data 
confirming heritability or a mode of 
inheritance at this time.
No specific data.
Species
• Spinal—pug, Rottweiler, French bulldog. 
• Brain—small brachycephalic breeds.
Dogs <3 years, range 2.5 months–13 years.
SIGNS
Spinal
• Owners report a slowly progressive ataxia 
and paresis involving all or just the pelvic 
limbs. • Fecal incontinence—common early 
sign of thoracolumbar diverticula, with 
urinary incontinence developing shortly after. 
• Owners do not usually report that the pet is 
in pain. In a study of 122 cases, 19% of the 
dogs had pain. • There may be prior history 
of previous spinal cord injury (due to trauma, 
intervertebral disc disease, or fibrocartila -
genous embolism). • There may be concurrent vertebral malformations at the site 
of the diverticula.
Brain
• Cerebellar signs. • Seizures.
Usually normal, although possible secondary 
consequences of the myelopathy include 
abrasions of the dorsal aspect of the toes, 
wearing of the nails, and urinary tract 
Spinal
• Neurologic signs reflect lesion 
localization—hindlimb involvement for 
thoracolumbar cysts and all limbs for cervical 
cysts. • Ataxia frequently characterized by 
hypermetria. • Paresis. • Proprioceptive 
placing deficits. • Fecal and/or urinary 
incontinence; urine retention (due to 
defective voiding). • Spinal reflexes may be 
reduced if the lesion is at the brachial or 
lumbosacral intumescence but otherwise are 
normal or increased. • Spinal pain is rarely 
elicited.
Brain
• Quadrigeminal cysts are frequently an 
incidental finding. However, extremely large 
cysts can produce compression of the 
cerebellum and brainstem. • Signs of 
cerebellar disease—hypermetria, intention 
tremor, wide-based stance. • Signs of 
brainstem compression—tetraparesis, head 
tilt. • Seizures (the relationship between the 
cyst and the presence of seizures is unclear).
CAUSES
• Several proposed etiologies. • Congenital 
malformation of the arachnoid mater (dilated 
septum posticum; in young dogs). 
• Secondary to traumatic injury to the 
arachnoid, causing adhesions and development 
of one-way valves for CSF flow. • Secondary 
to chronic microtrauma to the arachnoid, 
causing adhesions and development of 
one-way valves for CSF flow. This mechanism 
has been proposed for pugs with caudal 
thoracic subarachnoid cysts. Affected dogs 
may have hypoplasia of their articular facets 
leading to chronic instability.
• T raumatic spinal cord injury that damages 
the arachnoid mater. • Hypoplastic articular 
facets associated with subarachnoid 
diverticulae in certain dog breeds (pugs).
  DIAGNOSIS
• Distinctive features—slowly progressive, 
nonpainful paresis and ataxia with a hyper -
metric gait, and presence of fecal and/or urinary incontinence in an animal that is still 
ambulatory. • Any cause of focal myelopathy 
could cause the same neurologic presentation. 
• Intervertebral disc herniation. • Neoplasia. 
• T rauma. • Inflammatory or infectious 
myelitis. • Congenital vertebral/spinal 
malformation. • Intraspinal vascular 
Urinalysis may show evidence of urinary tract 
infection (pyuria, hematuria, proteinuria, and 
bacteriuria).
Aerobic urine culture if evidence of urinary 
IMAGING
• Thoracic radiography—in older patients to 
rule out metastatic neoplasia. • Spinal 
radiography—should be performed in all 
patients; typically unremarkable in patients 
with subarachnoid diverticulae. However, 
some patients may have evidence of spinal 
fractures, and occasionally there is evidence of 
a vertebral malformation (articular facet 
hypoplasia, spina bifida, hemivertebra, or 
block vertebra) colocalizing with the 
neurologic signs. • Myelography—focal 
dilation of the subarachnoid space most 
commonly located dorsally but sometimes 
located ventrally; the dilation may be 
multilobed. • CT myelography—further 
delineates the dilated subarachnoid space in 
transverse section; without intrathecal contrast, 
will not demonstrate the lesion. • MRI—
dilation of the subarachnoid space in sagittal 
and transverse section on T2-weighted images. 
T2-HASTE images provide even more 
definition of the CSF accumulation. The 
presence of active arachnoiditis can be detected 
on pre- and-postcontrast T1-weighted images.
CSF—to rule out a primary inflammatory 
process; may show mild inflammation as 
secondary consequence of the subarachnoid cyst.
• At surgery, adhesions may be evident in the 
subarachnoid space. Occasionally a thin cyst wall 
is apparent (this is unusual). • Histopathology of 
excised arachnoid—may show fibrosis or mild 
inflammation. • Histopathology of the spinal 
cord shows chronic compressive injury—loss of 
gray and white matter, Wallerian degeneration, 
  TREATMENT
• Patients with mild signs can be managed 
medically; surgery recommended for young 
dogs with moderate, progressive signs. 
• Nonambulatory patients should be

Canine and Feline, Seventh Edition  1303
Shospitalized for diagnostic workup and 
possible surgical decompression as soon as 
possible.
• Patients that have incomplete micturition 
should have their bladders manually expressed 
3–4 times a day. If this is not possible, their 
bladders should be catheterized in a sterile 
fashion once or twice a day. • Appropriate 
maintenance fluids should be administered in 
the immediate postoperative period. 
• Postoperative pain should be assessed 
regularly (q6h) and treated as needed with 
opiates and nonsteroidal anti-inflammatory 
drugs. • Surgical incisions should be ice 
packed for 5–10 minutes three times a day for 
24 hours after surgery and then should be hot 
packed for a similar period for an additional 
2–5 days. • Rehabilitation is important; a 
patient-specific rehabilitation program should 
be developed to include gait training and 
improvement of strength.
ACTIVITY
• Paretic and ataxic patients need to be 
restricted to nonslip, flat surfaces to avoid 
falling. • Exercise should be restricted to 
walking on a leash to avoid falling, but 
controlled exercise is important in 
maintaining muscle strength and joint 
integrity. • Postoperatively, patients need to 
be restricted to a small, well-padded space 
(crate) to ensure that they do not fall while 
the laminectomy site is healing. Limited 
controlled exercise should be performed 
during this period.
• Clients need to be educated on the 
implications of a chronic compressive 
myelopathy; permanent damage to the spinal 
cord has already occurred and may not be 
reversible. The primary aim of treatment is to 
prevent further deterioration, with a hope of 
also producing a clinical improvement. 
• There may be an initial deterioration 
immediately postoperatively; there is a small 
chance that this deterioration could be 
permanent. • Incontinence, if present, is 
likely to be permanent. • The disease may 
recur in spite of surgical therapy.
• Surgical decompression of spinal 
subarachnoid cysts is recommended in young 
dogs and can be attempted in older animals. 
• Marsupialization of the meninges may 
reduce the chance of a recurrence. • Surgical 
treatment of quadrigeminal cysts is only 
recommended if there are clear signs of 
compression of adjacent cerebellum and 
cerebral cortex. Direct surgical exploration 
and decompression or shunt placement can 
be attempted.  MEDICATIONS
• Anti-inflammatory doses of prednisone (0.5 
mg/kg orally once to twice a day) may 
improve signs and reduce inflammation. If 
there is no improvement, prednisone should 
be tapered and discontinued. • Omeprazole 
may reduce CSF production rate and improve 
signs. If there is no improvement it should be 
discontinued. • T reatment with antiepileptic 
drugs should be initiated in dogs with more 
than 1 seizure a month or cluster seizures. 
Choice of antiepileptic drug depends on a 
number of patient and client factors. 
Phenobarbital (starting at 2 mg/kg q12h), 
zonisamide (starting at 5–10 mg/kg q12h) 
and levetiracetam (starting at 20 mg/kg q8h) 
are all appropriate choices for first-line 
therapy.
Corticosteroids should be used with caution 
if the patient has urinary tract infection.
  FOLLOW-UP
• If response to prednisone is being assessed, 
the patient’s gait and postural reactions 
should be reassessed in 1–2 weeks. The 
owner’s assessment of continence is also 
important. • If there is a positive response to 
medical management, the patient should be 
monitored every 8–12 weeks for maintenance 
of the improvement over the next 6 months 
and then every 6–12 months. The owner 
should be instructed to call if deterioration in 
clinical signs is detected. • Surgical treatment—
patient reassessed at 7–10 days for suture 
removal, evaluation of incision, and to ensure 
that there is no deterioration in gait, level of 
pain, continence; reassessment at 1–3 months 
and every 6–12 months subsequently. 
Telephone updates are acceptable if the 
patient is doing well.
• Clients may encounter fecal and urinary 
• If incontinent, there is a predisposition to 
• Signs may recur at any time.
Spinal Diverticulae
• Surgical decompression produces a good 
long-term outcome (more than 1 year) in 
approximately 66% of dogs with spinal disease. • Age at onset of signs and duration 
of signs are associated with outcome. Dogs 
less than 3 years of age and with a short 
duration of signs (less than 4 months) are 
more likely to have a good long-term 
outcome. • There are limited data on the 
prognosis with medical management, but 
anecdotally the author can report a good 
long-term outcome in old dogs with mild 
signs when treated with prednisone and 
rehabilitation alone.
Quadrigeminal Cysts
Data on prognosis of quadrigeminal cysts 
managed medically or surgically are limited 
but suggests that a positive outcome can be 
attained with both treatment strategies.
Cervical cysts are more common in dogs <3 
years of age and thoracolumbar cysts are 
common in old pugs.
N/A
SYNONYMS
Arachnoid diverticula, arachnoid cyst, 
meningeal or leptomeningeal cyst.
SEE ALSO
Quadrigeminal Cyst.
http://www.ivis.org/advances/Vite/toc.asp
Dewey CW, Scrivani PV, Krotscheck U, et al. 
Intracranial arachnoid cysts in dogs. 
31(4):160–167.
Fisher SC, Shores A, Simpson ST. 
Constrictive myelopathy secondary to 
hypoplasia or aplasia of the thoracolumbar 
caudal articular processes in pugs: 11 cases 
242:223–229.
Gnirs K, Ruel Y, Blot S, et al. Spinal 
subarachnoid cysts in 13 dogs. Vet Radiol 
Ultrasound 2003, 44:402–408.
Mauler DA, De Decker S, De Risio L, et al. 
Signalment, clinical presentation and 
diagnostic findings in 122 dogs with spinal 
arachnoid diverticula. J Vet Intern Med 
2014, 28:175–181.
Skeen TM, Olby NJ, Muñana KR, Sharp NJ. 
Spinal arachnoid cysts in 17 dogs. J Am 
Anim Hosp Assoc 2003, 39:271–282.
Author  Natasha J. Olby(continued)  Subarachnoid Cysts (Arachnoid Diverticulum)

1304  Blackwell’s Five-Minute Veterinary Consult  
SSubinvolution of Placental Sites
  BASICS
OVERVIEW
• Failure or delay of normal postpartum 
uterine involution (normally requires 12–15 
weeks to complete).
• Failure of eosinophilic masses of collagen at 
placental sites to slough at 3–4 weeks post- 
partum.
• Failure of fetal trophoblastic cells to regress 
(normally occurs within 2 weeks); instead, 
they invade the maternal deep glandular 
endometrium and myometrium.
• Cause—unknown; hormonal or uterine 
basis not suspected based on coexistence of 
unaffected and subinvoluted placental sites in 
the same uterus.
• Bitch <3 years most common.
• Higher incidence in first litter.
• No breed predilections.
SIGNS
• Patient presented >12 weeks postpartum.
• Serosanguineous vulvar discharge beyond 
12 weeks postpartum.
• Typically no systemic signs; rare occurrence 
of hypovolemic shock from hemorrhage.
• Serosanguineous vulvar discharge.
• Firm, spherical structures within uterus on 
Unknown; thought unlikely to be hormonal 
because only some of the placental sites may be 
involved. Also thought unlikely to be uterine 
disease because of high first litter prevalence.
  DIAGNOSIS
• Metritis—differentiated by vaginal cytology 
and physical examination.
• Vaginitis—differentiated by vaginal cytology.
• Vaginal neoplasia—differentiated by vaginal 
cytology and vaginal endoscopy.
• Uterine neoplasia—differentiated by 
ultrasonography or exploratory laparotomy.
• Cystitis—differentiated by vaginal cytology 
and urinalysis obtained by cystocentesis.
• Coagulopathy—differentiated by clotting 
times, platelet count.
• T rauma.
• Endogenous estrogen stimulation—bitch with 
an extremely shortened interestrous interval.
• Exogenous estrogen stimulation—oral 
medication or contact with topical hormone 
replacement product on human skin, 
bedding, or clothing.CBC/BIOCHEMISTRY/URINALYSIS
• Serology for Brucella canis  negative.
• Serum progesterone <2 ng/mL
IMAGING
Uterine ultrasonography—focal uterine wall 
thickening; possible echogenic fluid in the 
lumen
• Vaginal cytologic examination—key for 
diagnosis; reveals erythrocytes and parabasal 
epithelial cells; may note pathognomonic 
trophoblastic cells (polynucleated, heavily 
vacuolated).
uterine culture—if vaginal cytologic 
examination or hemogram supports a 
diagnosis of secondary metritis.
• Gross—sites characterized by a thickened, 
hemorrhagic area that may be nodular.
• Histopathologic—definitive diagnosis; 
eosinophilic collagen masses with trophoblasts 
extending into the myometrium.
  TREATMENT
• Spontaneous remission—occurs in most 
patients before or at next cycle; medical 
therapy is generally not warranted.
• Medical—for rare development of anemia, 
metritis, or peritonitis.
• Severely affected patients—may require 
blood transfusion (rare).
• Warn owner of the rare possibility of 
excessive hemorrhage; instruct owner to 
monitor mucous membrane color.
• Ovariohysterectomy—curative; treatment 
of choice if future breeding not desired.
• Surgical curettage of subinvoluted sites—may 
also be performed; effectiveness unknown.
• Oxytocin generally not successful.
• Ergonovine 10–30 μg/kg IM once; do not 
use if uterus friable.
• Small study showed response to megestrol 
acetate 0.1 mg/kg PO q24h for 1 week, then 
0.05 mg/kg PO q24h daily for 1 week; 5 of 6 
treated bitches were successfully bred, with 
normal parturition and puerperal periods.
• Ecbolics—may cause uterine rupture.• Progestational drugs—increase the risk of 
metritis, which may mimic pyometra or 
induce cystic endometrial hyperplasia.
  FOLLOW-UP
• Mucous membrane color and amount of 
• Packed cell volume or hematocrit—if 
anemia is a concern.
• Changes in discharge color or odor and 
vaginal cytologic examination and culture—
diagnose secondary infection.
Infection, blood-loss anemia, or uterine 
rupture—rare.
• Spontaneous resolution—the usual outcome 
in the majority of cases.
• Recurrence—not expected, occurs rarely.
• Prognosis for future reproduction—
excellent with spontaneous resolution.
Reproduction. Philadelphia, PA: Saunders, 
2004, pp. 808–834.
PN, eds., Canine and Feline 
Voorhorst MJ, van Brederode JC, Albers-
Wolthers CHJ, et al. Successful treatment 
for subinvolution of placental sites in the 
bitch with low oral doses of progestagen. 
Reprod Domest Anim 2013, 48:840–843.

Canine and Feline, Seventh Edition  1305
S  BASICS
OVERVIEW
• Excitement and submissive urination occur 
as distinct behavioral presentations but may 
overlap in some patients.
• Submissive urination is related to fearful 
responses—animal perceives potential threat 
or danger during interaction and displays 
submissive behavior, including urination, as 
appeasement gesture to abort potential 
escalation of aggressive interactions.
• Generally seen in interaction with people; 
however, submissive urination may occur 
during interactions with other animals, 
especially conspecifics.
• Onset as puppy in dogs of either sex: 
generally <1 year old.
• Anecdotally higher incidence in some small 
breeds, e.g., dachshund, cocker spaniel.
• Not observed in cats.
SIGNS
• Excitement—loss of urine control in 
situations of high arousal, e.g., greeting 
people, anticipation of activities such as walks 
or car rides; no actual urination posturing 
seen—urine is expelled while dog is engaged 
in activities such as jumping up or play; dog 
does not necessarily show submissive 
behavior.
• Submissive/fear—expelling small amounts of 
urine during interactions with people or other 
animals or in frightening situations; partial or 
full squatting position; dog may lift one hind 
leg partially for inguinal presentation.
• Dogs may be excited and aroused yet also 
submissive or fearful during greeting—when 
there are competing motivations this might 
therefore be described as conflict induced; the 
approach may be active with tail wagging and 
crouching/low body posture.
• Administration of medications that reduce 
urethral competence or increase urine 
production (e.g., corticosteroids, sedatives).
• Domineering training styles or interaction 
patterns.
  DIAGNOSIS
• Incontinence, ectopic ureter, patent 
urachus.
• Disorders of urethral competence (which 
may increase severity or frequency of 
urination during submissive or excitement 
urination).• Disorders causing polyuria/polydipsia may 
decrease pet’s ability to maintain bladder 
control.
Indicated only to rule out medical disorders.
IMAGING
  TREATMENT
Excitement Urination
• Avoid arousing situations.
• Do not greet dog when aroused/excited—  
greet dog away from front door and several 
minutes after arrival only after dog is calm.
• When entering home, toss treats away to 
redirect and distract pet; over time gradually 
transition to tossing treats closer to person 
and eventually hand treats to pet when pet 
sits calmly on cue.
• Avoid high-pitch excited speech around 
pet; avoid eye contact if it arouses/excites 
the pet.
• Teach owner to reinforce calm behavior and 
teach behaviors incompatible with high 
arousal, e.g., sit or lie down for greetings and 
before walks.
• Owners should interact with pet in 
emotionally neutral, low-key manner.
Submissive/Fear Urination
• Avoid threatening or confrontational 
interactions; do not lean over pet; do not 
punish or raise voice with pet; avoid eye 
contact.
• Avoid confrontational training styles/
• Avoid deep, loud, or high-pitch excited 
speech while around or interacting with the 
pet.
• Move slowly and calmly around pet to 
avoid potential startling or threatening 
• Squat down or greet/interact with pet while 
sitting in chair or on floor with the body 
turned partially away from the dog.
• Redirection or distraction with food treats 
or toys; toss treats away to redirect and 
distract pet; over time can gradually transition 
to tossing treats closer to person and 
eventually hand treats to pet when pet sits 
calmly on cue.
• Teach behaviors with positive reinforcement 
that are incompatible with submissive 
posturing using positive reinforcement (food 
treats)—pet sitting upright with head and 
ears up and forward; eye contact.
• Owner should recognize and identify 
triggers and turn and walk away or back away 
if pet begins to show submissive posturing.  MEDICATIONS
• Medications generally not indicated but 
could consider:
 ◦Phenylpropanolamine 12.5–50 mg PO 
up to q8h temporarily to increase urethral 
sphincter tone while behavior modification 
is taking effect.
 ◦Imipramine 2.2–4.4 mg/kg PO q12h or 
clomipramine 1–3 mg/kg PO q12h to 
increase urinary retention through 
anticholinergic effects; serotonin and 
norepinephrine properties can help reduce 
excitement or fear that contribute to 
  FOLLOW-UP
Prognosis is good if owners can follow simple 
behavior modification steps; a number of pets 
will improve with maturity alone.
SEE ALSO
Case L. Canine and Feline Behavior and 
T raining. Clifton, NY: Delmar Cengage 
Learning, 2010, pp. 193–194.
Hart B, Hart L, Bain M. Canine and Feline 
Behavior Therapy, 2nd ed. Ames, IA: 
Blackwell, 2006, pp. 190–191.
Lindsay S. Applied Dog Behavior and 
T raining, Vol. 2. Ames, IA: Iowa State 
University Press, 2001, pp. 294–295.
Author  Lore I. Haug
Consulting Editor  Gary M. LandsbergSubmissive and Excitement Urination—Dogs

1306  Blackwell’s Five-Minute Veterinary Consult  
SSuperficial Necrolytic Dermatitis
  BASICS
OVERVIEW
• Uncommon in dogs; rare in cats.
• Usually a cutaneous marker for advanced 
liver disease with or without concurrent 
• Shih tzu, Shetland sheepdog, West 
Highland white terrier, cocker spaniel 
• Older dogs.
SIGNS
• Skin—lesions may precede clinical evidence of 
internal disease by weeks or months; erythema, 
crusts, and erosions/ulcerations affecting the 
muzzle, mucocutaneous areas of the face, pinna, 
distal limbs (especially elbows and hocks), feet, 
perineum, perianal area, and external genitalia.
• Footpads—hyperkeratotic with fissures and 
ulcerations; pain when walking.
• Pruritus absent to severe.
• Secondary bacterial and/or yeast infection.
• Feline—alopecia and scaling of the limbs 
and trunk (two cases); erythema, ulceration, 
crusting, and alopecia of the limbs and trunk 
(one case); crusts and hyperkeratosis of paw 
pads (one case).
• Specific cause unknown.
• Cutaneous nutritional deprivation—  
probably hypoaminoacidemia and/or 
deficiencies in essential fatty acids and zinc; 
due to metabolic abnormalities caused by 
hyperglucagonemia, liver dysfunction, or a 
• Usually associated with advanced liver 
disease with or without concurrent diabetes 
mellitus.
• Rarely associated with pancreatic or 
extrapancreatic glucagon-secreting tumor, 
ingestion of mycotoxins, or long-term 
phenobarbital and phenytoin therapies.
• Feline—one case each of pancreatic 
carcinoma, hepatic carcinoid, hepatopathy, 
and hepatopathy and intestinal lymphoma.
  DIAGNOSIS
• Zinc-responsive dermatosis.• Toxic epidermal necrolysis.
• Feline exfoliative skin diseases—thymoma-
associated exfoliative dermatitis and cutane-
ous epitheliotropic lymphoma.
• Red blood cell abnormalities—micro -
cytosis, polychromasia, anisocytosis, poikilo  - 
cytosis, target cells.
• Alkaline phosphatase, alanine aminotrans-
ferase, and aspartate aminotransferase—  
significant elevation.
• Total bilirubin—variably high.
• Albumin—frequently low.
• Borderline or frank hyperglycemia— 
common.
• Bile acid levels—variably high.
• Liver biopsy—vacuolar hepatopathy with 
parenchymal collapse and nodular 
• Elevated plasma glucagon levels—present 
with glucagon-secreting tumors; variable with 
chronic liver disease.
• Hypoaminoacidemia—common.
• Aminoaciduria.
• High insulin levels may be noted.
• Sulfobromophthalein retention—typically 
IMAGING
• Ultrasonography—“honeycomb” liver 
pattern in advanced hepatopathy.
• Usually unremarkable with pancreatic or 
extrapancreatic glucagon-secreting tumor 
unless large enough to visualize.
Skin biopsy—sample early lesions; include 
crusts and avoid eroded/ulcerated lesions.
• Parakeratotic hyperkeratosis with high-level 
intracellular and intercellular epidermal 
edema; irregular epidermal hyperplasia and 
mild-to-severe superficial perivascular 
• Chronic lesions—marked parakeratotic 
hyperkeratosis and epidermal hyperplasia.
  TREATMENT
• Supportive care for systemic signs.
• Surgical excision of glucagon-secreting 
tumors—can be curative if no metastasis.
• Oral nutritional support—high-quality 
protein diet or protein supplement for 
non-encephalopathic cases; 3–6 cooked whole 
eggs or yolks per day.
• Hydrotherapy and shampoos—remove 
crusts; lessen pruritus and pain.  MEDICATIONS
• Specific treatment—attempt to correct the 
underlying disease if possible.
• Nonspecific therapy—antibiotics and 
antifungal drugs for secondary skin 
• Amino acid hyperalimentation—IV 
administration of a 8.5–10% crystalline 
amino acid solution (e.g., Aminosyn®) 25 
mL/kg, administered over 6–8 hours; 
repeated weekly or as needed for symptom 
relief (≥10 infusions may be required). Oral 
amino acid therapy may be beneficial.
• IV lipid infusion—may improve outcome 
when combined with IV amino acid therapy 
(7 mL/kg of 20% Intralipid®).
• Octreotide (somatostatin analogue)  
2–3.2 μg/kg SC q6–12h as maintenance 
therapy for patients with nonresectable 
glucagon-secreting tumors.
• Glucocorticoids—can improve skin lesions; 
use carefully; encourages development of 
• Colchicine 0.03 mg/kg/day may be 
beneficial in advanced liver disease.
• Zinc methionine 2 mg/kg/day—adjunctive 
therapy.
• Essential fatty acids—adjunctive therapy.
  FOLLOW-UP
• Bacterial and/or yeast skin infections.
• Metastasis of glucagon-secreting tumors.
• Prognosis poor; survival time reported as 6 
months after development of skin lesions.
• Rare incidence of recovery if hepatic/
metabolic insult resolves.
N/A
Resnick

Canine and Feline, Seventh Edition  1307
S  BASICS
Repetitive supraventricular premature 
depolarizations that originate from a site 
other than the sinus node, such as the atrial 
myocardium or atrioventricular (AV) nodal 
tissue.
ECG Features (Figure 1)
• Heart rate—rapid, 180–350 bpm in dogs.
• Rhythm usually very regular (constant R-R 
interval) and may be sustained, but there can be 
frequent or infrequent short runs of supra -
ventricular tachycardia (SVT), so-called 
paroxysmal SVT. Rarely, the rhythm will be 
irregular, suggesting abnormal automaticity as 
the etiology. • Usually QRS complexes typical 
of normal sinus complexes, i.e., narrow with a 
normal mean electrical axis. In some cases a 
coexisting bundle branch block or aberrant 
ventricular conduction makes it difficult, if not 
impossible, to differentiate an SVT from a 
ventricular tachycardia by examining the ECG. 
• P waves can be normal or abnormal and 
typically differ in configuration from the sinus P 
waves. P waves may be buried in the previous T 
wave and therefore not visualized. • AV 
conduction is usually normal (1:1), but various 
levels of functional second-degree AV block may 
occur at higher atrial rates (2:1, 3:1, 4:1, etc.).
• SVT may be primary (idiopathic) or 
secondary to other cardiac diseases, generally 
those creating atrial enlargement. • May result 
from a reentrant mechanism or from abnormal 
automaticity in an ectopic focus. Reentrant 
SVT typically produces a very regular rhythm; 
SVT due to an automatic focus in atrial 
myocardium can produce an irregular rhythm.
• Most cases in dogs respond to drugs that 
specifically alter conduction and refractoriness in 
the AV nodal tissue, suggesting AV nodal reentry as the mechanism. • Recent electrophysiologic 
studies revealed that some SVT in dogs is related 
to a congenital accessory pathway between the 
atria and ventricles, allowing electrical impulses 
to travel freely between the atria and ventricles 
without traversing the AV node and without 
conduction delay; in these cases, the SVT is 
caused by reentry through the accessory pathway 
and the AV node.
• Cardiovascular—congestive heart failure 
(CHF) may develop secondary to progressive 
myocardial failure associated with a 
chronically high heart rate (so-called 
tachycardia-induced myocardial failure). 
• Neuromuscular—syncope or generalized 
episodic weakness due to reduced cardiac 
output and oxygen delivery.
Species
SIGNS
• Clinical signs may relate to the underlying 
cause. • Dogs with slow SVT or infrequent 
paroxysmal SVT may exhibit no clinical signs. 
• Dogs with fast SVT (heart rate usually 
>300 bpm) generally exhibit episodic 
weakness or syncope.
• Owners are generally unaware of the 
arrhythmia. • Coughing or breathing 
abnormalities in dogs with CHF . • Episodic 
• Rapid, usually regular heart rhythm. However, 
in dogs with paroxysmal SVT, rhythm may be 
normal and regular during the physical exam. 
• May have evidence of poor peripheral 
perfusion—pale mucous membranes, prolonged 
capillary refill time, and weak pulses. • May 
have no signs other than rapid heart rate. • Findings may reflect underlying cardiac 
condition (e.g., heart murmur).
CAUSES
• Chronic valvular disease. • Cardiomyopathy. 
• Congenital heart disease. • Cardiac neoplasia. 
• Systemic disorders. • Ventricular preexcitation. 
• Electrolyte imbalances. • Digoxin toxicity. 
Heart disease.
  DIAGNOSIS
• Sinus tachycardia. • Atrial flutter. • Atrial 
fibrillation. • Ventricular tachycardia (SVT 
with right bundle branch block or aberrant 
conduction can look like ventricular 
tachycardia; resolution of arrhythmia after 
lidocaine administration usually confirms 
ventricular tachycardia).
IMAGING
• Echocardiography (including Doppler 
studies) may help characterize the type and 
severity of underlying cardiac disorders. 
Echocardiography is also important for 
assessing myocardial function in patients with 
idiopathic SVT. • When viewed on an 
echocardiogram during bursts of SVT, the left 
ventricle has a normal end-systolic diameter 
and a small end-diastolic diameter, resulting 
in a decreased shortening fraction because of 
inadequate filling. • Usually left or right atrial 
enlargement in dogs with SVT secondary to 
other cardiac disorders.
• Long-term ambulatory (Holter) recording 
of the ECG may detect paroxysmal SVT in 
cases of unexplained syncope. This is 
generally only helpful if syncope is occurring 
regularly within a 24- to 48-hour period. 
Figure 1 .
Sinus with an atrial premature complex and paroxysmal SVT. Abrupt initiation and termination of the tachycardia help distinguish it from sinus tachycardia 
(lead II, 50 mm/s, 1 cm = 1 mV). (Source: From Tilley LP . Essentials of Canine and Feline Electrocardiography, 3rd ed. Baltimore: Williams & Wilkins, 1992. 
Reprinted with permission of Wolters Kluwer.)Supraventricular Tachycardia

1308  Blackwell’s Five-Minute Veterinary Consult  
SHolter monitors may also help characterize 
the rate and frequency of sustained SVT and 
are useful in evaluating the efficacy of therapy. 
• Event (loop) recorders may detect paroxysmal 
SVT in patients with infrequent episodes of 
syncope (<q24–48h). • Sustained SVT must 
be distinguished from sinus tachycardia 
because the two arrhythmias have different 
implications and treatment. A precordial 
thump may help differentiate sinus 
tachycardia from SVT when the heart rate is 
in the 150–250 bpm range; it will usually 
stop an SVT for at least 1 or 2 beats, while a 
sinus tachycardia will not slow. A vagal 
maneuver (e.g., ocular pressure or carotid 
sinus massage) may break an SVT abruptly 
but only gradually slows sinus tachycardia.
  TREATMENT
• Asymptomatic patients can be managed on 
an outpatient basis; patients with a sustained 
SVT or signs of CHF should be hospitalized 
until stable. • SVT is a medical emergency in 
dogs that exhibit weakness and collapse; 
nonpharmacologic interventions that may 
break an SVT include vagal maneuvers, 
precordial thump, and electrical cardioversion. 
• Vagal maneuvers are often unsuccessful but 
may be used initially because of their ease of 
administration and noninvasive nature. 
• Delivering a precordial thump can 
successfully (>90% of the time) terminate an 
SVT in dogs, but this maneuver may break 
the rhythm for only a brief period. At other 
times the rhythm remains converted. To 
perform a precordial thump, the dog is placed 
on its right side and the left apex beat is located. 
This region is then “thumped” with a fist while 
recording the ECG. • Emergency medical 
therapy is required in patients in which a 
precordial thump is unsuccessful (see below).
T reat CHF and correct any underlying 
electrolyte or acid–base disturbances.
ACTIVITY
Restrict until arrhythmia has been controlled.
DIET
Mild to moderate sodium restriction if in 
CHF .
Owners should observe patients closely for 
signs of low cardiac output such as weakness 
and collapse.
Consider transvenous catheter ablation for 
patients with accessory pathways.  MEDICATIONS
Emergency Therapy
• Administer one of the following: ◦ Calcium 
channel blockers—diltiazem 0.05–0.25 mg/kg 
IV over 5–15 minutes or verapamil 0.05 mg/kg 
boluses IV over 3–5 minutes up to 3 times; 
verapamil more likely to cause hypotension. 
◦ β-Adrenergic blockers—esmolol 0.25–0.5 
mg/kg slow IV bolus administration followed 
by a CRI of 50–200 μg/kg/min; moderate-to-
severe myocardial failure is a relative contra -
indication to the administration of β-adrenergic 
blockers. ◦ Electrical cardioversion or 
intracardiac electrophysiologic pacing methods 
may be considered in extreme cases.
• Digoxin—administer at either maintenance 
oral dose or double the maintenance dose for 
the first day to produce a therapeutic serum 
concentration more rapidly; contraindicated in 
patients with accessory pathways. 
• β-Adrenergic blocker—atenolol 0.2–1 mg/kg 
PO q12–24h as long as there is no underlying 
moderate-to-severe myocardial failure. 
• Diltiazem is the calcium channel blocker of 
choice for long-term control of SVT; dose 
required to control SVT has not been reported 
in the dog. Diltiazem used more frequently to 
control ventricular rate in patients with atrial 
fibrillation at a dosage of 0.5–1.5 mg/kg PO 
q8h. In our clinic, we generally start in this 
range but almost always need to increase the 
dose to 2–3 mg/kg PO q8h to effectively 
control SVT. • Class I antiarrhythmic agents 
such as quinidine and procainamide can be 
tried when the aforementioned drugs are 
ineffective or when SVT is thought to be due 
to an automatic, rather than a reentrant, 
rhythm. SVT caused by an automatic atrial 
focus may produce an irregular rhythm and 
may be refractory to conventional drug therapy. 
When SVT is due to an accessory pathway, 
these drugs are more effective.
Avoid calcium channel blockers in combina-
tion with beta-blockers; clinically significant 
bradyarrhythmias can develop.
Calcium channel blockers and β-adrenergic 
blockers have negative inotropic properties 
and should be used cautiously in dogs with 
documented myocardial failure.
• Adenosine 1–12 mg IV rapidly—very 
expensive and short-lived. • Propranolol 
0.02 mg/kg slow IV boluses up to a total dose of 0.1 mg/kg—long half-life after IV 
administration, also significant β2-blocking 
effects and is generally not recommended 
unless no other alternative is available.
  FOLLOW-UP
Serial ECG or Holter monitoring.
Syncope and CHF .
Most are controlled effectively with 
Accessory pathways in some patients.
In young dogs without evidence of structural 
heart disease, suspect a reentrant tachycardia 
involving an accessory pathway.
SYNONYMS
Atrial tachycardia, junctional tachycardia.
SEE ALSO
Atrial Fibrillation and Atrial Flutter.
heart failure. • ECG = electrocardiogram. 
Kraus MS, Gelzer ARM. T reatment of cardiac 
Saunders Elsevier, 2016, pp. 313–329,
Electrocardiography of the dog and cat. In: 
Diagnosis of Arrhythmias, 2nd ed. Milano, 
Wright KN. Assessment and treatment of 
supraventricular tachyarrhythmias. In: 
Therapy XIII. Philadelphia, PA: Saunders, 
1999, pp. 726–730.
available online(continued)  Supraventricular Tachycardia

Canine and Feline, Seventh Edition  1309
SSyncope
  BASICS
Temporary loss of consciousness and vascular 
tone associated with loss of postural tone, 
followed by spontaneous recovery.
Inadequate cerebral perfusion and delivery of 
oxygen and metabolic substrates leads to loss 
of consciousness and motor tone; impaired 
cerebral perfusion can result from changes in 
vasomotor tone, cerebral disease, and low 
cardiac output caused by structural heart 
disease or arrhythmias.
• Nervous.
Species
• Sick sinus syndrome—cocker spaniel, 
terriers, pug, dachshund.
• Ventricular arrhythmias—boxer, German 
More common in old animals.
CAUSES
Cardiac Causes
• Bradyarrhythmias—sinus bradycardia, 
sinus arrest, second-degree atrioventricular 
(AV) block, complete AV block, atrial 
• Tachyarrhythmias—ventricular tachycardia, 
supraventricular tachycardia, atrial fibrillation.
• Low cardiac output (nonarrhythmic)—
cardiomyopathy, degenerative valve disease, 
subaortic stenosis, pulmonic stenosis, 
pulmonary hypertension, heartworm disease, 
pulmonary embolism, cardiac tumor, cardiac 
Neurologic and Vasomotor Instability
• Vasovagal syncope—emotional stress and 
excitement may cause heightened sympathetic 
stimulation, leading to transient tachycardia 
and hypertension, which is followed by a 
compensatory rise in vagal tone, leading to 
excessive vasodilation without a compensa-
tory rise in heart rate and cardiac output; 
bradycardia often occurs.
• Situational syncope refers to syncope 
associated with coughing, defecation, 
urination, and swallowing.
• Carotid sinus hyperactivity may cause 
hypotension and bradycardia—often the cause 
of syncope when one pulls on a dog’s collar.Miscellaneous Causes
• Drugs that affect blood pressure and 
regulation of autonomic tone.
• Hypoglycemia, hypocalcemia, and hypo  - 
natremia (rare).
• Hyperviscosity syndromes (e.g., polycythemia 
and paraproteinemia) cause sludging of blood 
and impaired cerebral perfusion (rare).
• Heart disease.
• Drug therapy—vasodilators (e.g., calcium 
channel blockers, angiotensin-converting 
enzyme (ACE) inhibitors, hydralazine, and 
nitrates), phenothiazines (e.g., acepromazine), 
antiarrhythmics, and diuretics.
  DIAGNOSIS
• Must differentiate from other altered states 
of consciousness, including seizures and 
narcolepsy (a sleep disorder).
• Seizures are often associated with 
prodromal and postictal periods; syncope 
occurs without warning, and animal usually 
has rapid, spontaneous recovery. Unlike 
syncope, seizure activity is usually associated 
with tonic–clonic muscle activity rather than 
flaccidity.
• Like syncope, narcolepsy occurs suddenly, 
results in muscle flaccidity, and resolves 
spontaneously. Unlike syncope, narcolepsy 
can last for minutes and can be terminated by 
loud noises or harsh external stimuli.
collapse such as musculoskeletal disease and 
neuromuscular disease (e.g., myasthenia 
gravis), which are not associated with loss of 
consciousness.
Differential Causes (Figure 1)
• Syncope with excitement or stress suggests 
vasovagal syncope.
• Syncope with coughing, urination, or 
defecation suggests situational syncope.
• Syncope with exercise suggests low-output 
states associated with arrhythmias or 
structural heart disease.
• A murmur supports heart disease but does 
not confirm cardiac cause for syncope.
• Hypoglycemia or electrolyte disturbance in 
• If animal is hypoglycemic, measure insulin 
concentration on same blood sample. 
Calculate an amended insulin: glucose ratio 
to rule out insulinoma.• If animal is hyponatremic or hyperkalemic, 
consider an adrenocorticotropic hormone 
(ACTH) stimulation test.
• If low cardiac output is suspected, rule out 
occult heartworm disease.
IMAGING
• Radiography may detect structural heart disease, 
evidence of pulmonary embolism, or vascular 
changes supportive of heartworm disease.
• Echocardiography may detect structural 
heart disease (including tumors) or pericardial 
disease that could lower cardiac output.
• Doppler echocardiography may aid in the 
diagnosis of pulmonary hypertension.
• Pulmonary angiography may detect 
• CT and MRI may detect pulmonary embolism 
or heart-based and carotid body masses.
• Ventilation perfusion scintigraphy may 
detect pulmonary embolism.
• Have client monitor heart rate during any 
syncopal episode.
• Electroencephalogram, CT of the head, 
cerebrospinal fluid tap if CNS origin suspected.
• Post-exercise ECG may reveal intermittent 
• Holter monitoring (24-hour ECG record -
ing) or use of an ECG event (loop) recorder—
useful for evaluating arrhythmic causes.
• Carotid sinus massage with ECG and blood 
pressure monitoring useful in evaluating 
carotid sensitivity.
  TREATMENT
• Avoid or discontinue medications likely to 
precipitate syncope.
• T reat as outpatient unless important heart 
disease is evident.
• Minimize stimuli that precipitate episodes.
• Low cardiac output—minimize activity.
• Vasovagal—minimize excitement and 
stress.
• Cough—remove collar.
Pacemaker implantation for sick sinus 
syndrome, advanced AV block, and persistent 
Bradyarrhythmias
• Correct metabolic causes.

1310  Blackwell’s Five-Minute Veterinary Consult  
S
• Anticholinergics (e.g., atropine, propantheline 
bromide, hyoscyamine sulfate).
• Sympathomimetics (e.g., isoproterenol, 
bronchodilators).
• Phosphodiesterase III inhibitor (i.e., cilostazol) 
may be beneficial in sick sinus syndrome
• Pacemaker implantation in some patients.
Tachyarrhythmias
• Atrial arrhythmias—administer digoxin, 
beta-blocker, or diltiazem.
• Ventricular arrhythmias—administer 
lidocaine, mexiletine, sotalol, or beta-blocker.
Low Cardiac Output
Institute treatment to improve cardiac output, 
which varies according to specific cardiac 
disease.
Vasovagal
• Theophylline or aminophylline—some-
times helpful; mechanism of action in this 
setting is unclear.
• Beta-blockers (e.g., atenolol, propranolol, 
and metoprolol) may indirectly prevent vagal 
stimulation by blocking the initial sympa-
thetic response.
• Anticholinergics may blunt the vagal response.  FOLLOW-UP
ECG or Holter monitoring to assess efficacy 
of antiarrhythmic therapy.
• Death.
• T rauma when collapse occurs.
Most noncardiac causes are not life-threaten-
ing; cardiac causes may be treated, but 
syncope in patients with cardiac disease may 
suggest higher mortality risk.
SEE ALSO
• Narcolepsy and Cataplexy.
Epilepticus)—Cats.• Seizures (Convulsions, Status 
Davidow EB, Proulx J, Woodfield JA. 
Syncope: pathophysiology and differential 
2001, 2:609–618.
Rasmussen CE, Falk T, Domanjko Petrič A, 
et al. Holter monitoring of small breed dogs 
with advanced myxomatous mitral valve 
disease with and without a history of 
syncope. J Vet Intern Med 2014, 
28(2):363–370.
available onlineSyncope
Perform Histor y, Physical
Exam, Baseline ECG, CBC
Serum Chemistr y Profile
and F asting Blood GlucoseDiagnostic Not Diagnostic
Vasovagal Syncope
Situational Syncope
Drug-Induced
Metabolic DerangementPost-e xcercise ECG
Holter Monitor ing
ECG Ev ent (Loop) Recorder
Electroph ysiologic Studies
Not Diagnostic
Consider lo w cardiac output
states or neurologic disease
Suggesti ve of Carotid Sinu s
Syncope
(collapse when pull on collar)
ECG and b lood pressure monitor ing
while perf orming carotid massageSuggestiv e of CNS Disease
(possib le seizure , local
neurologic findings)Suggesti ve of Reduced Cardiac
Output
(heartworm disease ,
cardio myopathy, subaor tic
stenosi s, pulmona ry embolism,
pulmonic stenosis)
Occult Hear tworm Test
Echocardiogra m
Cardiac Cathete rization
Lung Scan f or Pulmona ry EmbolismCSF Tap
EEG
Head CT Scan
Figure 1 .
Algorithm for syncope.Syncope  (continued)

Canine and Feline, Seventh Edition  1311
SSynovial Cell Sarcoma
  BASICS
OVERVIEW
• Synovial sarcoma (or synovial cell sarcoma) 
is a malignant neoplasm arising from type B 
synoviocytes of the joint capsule or tendon 
sheath.
• Synovial sarcomas are locally aggressive and 
have moderate metastatic potential. At 
diagnosis up to 32% of dogs have metastases 
with the most common sites being the local 
lymph node and lungs.
• The disease is seen most commonly in the 
appendicular skeleton, specifically affecting 
the elbow, stifle, and shoulder joints. Synovial 
sarcoma must be differentiated via immuno­
histochemistry from other types of joint 
tumors, namely histiocytic sarcoma, which 
has a more aggressive biologic behavior and a 
worse prognosis.
• Dog—often large ­breed dogs of either sex, 
predisposition of flat ­coated and golden 
retrievers, mean age of 9 years.
• Cat—rarely reported.
SIGNS
• Slowly progressive lameness.
• Palpable mass.
• Clinical course may be protracted over 
months to years.
Unknown
  DIAGNOSIS
• Other primary neoplasia (e.g., histiocytic 
sarcoma, chondrosarcoma, osteosarcoma).
• Other bone or joint diseases (e.g., 
osteoarthritis, osteomyelitis).
No consistent abnormalities.
N/A
IMAGING
• Radiographs of the affected joint often 
demonstrate both bone and joint involvement 
with periarticular soft tissue swelling and 
periosteal reaction or multiple punctate 
osteolytic changes in adjacent bone.
• Thoracic radiographs should be obtained to 
screen for metastatic disease.
• Abdominal ultrasonography should be 
performed to evaluate intra ­abdominal lymph 
nodes in animals with tumors on the pelvic 
limbs.DIAGNOSTIC PROCEDURES
• Regional lymph nodes should be palpated 
and fine ­needle aspirates performed.
• Biopsy and immunohistochemistry to 
differentiate from histiocytic sarcoma 
(histiocytic sarcoma is CD18+).
  TREATMENT
Limb amputation; forequarter, coxofemoral 
disarticulation or hemipelvectomy to 
minimize risk of local recurrence.
• The role of chemotherapy for synovial 
sarcomas is not known; however, doxorubicin 
is commonly utilized for the treatment of 
sarcoma histologies.
• Pain management with analgesic drugs as 
N/A
  FOLLOW-UP
Monitor for local recurrence and pulmonary 
metastatic disease every 2–3 months for the 
first year; every 6 months thereafter.
• Localized disease at diagnosis—prognosis is 
excellent; median survival time >36 months. 
Lesser dose of surgery (i.e., marginal excision) 
is associated with poorer prognosis compared 
to limb amputation.
• Metastatic disease at diagnosis—prognosis 
is poor; median survival time <6 months. 
High ­grade tumors (high mitotic rate, high 
percent tumor necrosis, high nuclear 
pleomorphism) also confer a worse prognosis.
Do not breed animals that are receiving 
Craig LE, Julian ME, Ferracone JD. 
Diagnosis and prognosis of synovial tumors 
in dogs: 35 cases. Vet Pathol 2002, 
39:66–73.
Fox DB, Cook JL, Kreeger JM, et al. Canine 
synovial sarcoma: a retrospective assessment of described prognostic criteria in 16 cases 
(1994–1999). J Am Anim Hosp Assoc 
2002, 38(4):347–355.
acknowledge the prior contribution of Laura 
E. Selmic.

1312  Blackwell’s Five-Minute Veterinary Consult  
SSyringomyelia and Chiari-Like Malformation
  BASICS
• Chiari-like malformation (CM) is 
characterized by overcrowding of the cranio- 
cervical junction (CCJ) and obstruction of 
CSF channels (brachycephalic obstructive 
CSF channel syndrome [BOCCS]); may be 
associated with behavioral and clinical signs 
of pain (CM-P).
• In syringomyelia (SM), fluid-filled cavities 
(syringes/syrinxes) develop within the spinal 
cord; it is a potential consequence of 
BOCCS.
• Myelopathy can develop with wide SM 
and, if the dorsal horn is involved, phantom 
scratching and torticollis.
CM
A complex disorder associated with brachy- 
cephaly involving skull base shortening, 
craniofacial hypoplasia, and CCJ abnor -
malities including increased proximity of 
the atlas to skull and increased odontoid 
angulation. There may a relative increase in 
parenchymal volume; for example, cavalier 
King Charles spaniels (CKCS) have greater 
cerebellar volume compared to other breeds. 
The reduced cranial capacity results in 
rostrotentorial neuroparenchymal crowding 
with rostral forebrain flattening, small and 
ventrally orientated olfactory bulbs, 
displacement of the neural tissue to give 
increased height of the cranium and further 
reduction of the functional caudotentorial 
space with hindbrain herniation. CM is often 
compared to human chiari type I and 0 
malformation, however it is more similar to 
complex craniosynostosis syndromes 
(premature fusion of multiple skull sutures).
SM
In addition to the above brachycephalic 
changes, dogs with SM are more likely to 
have CCJ abnormalities, including rostral 
displacement of the atlas with increased 
odontoid angulation, causing craniospinal 
junction deformation and medulla oblongata 
elevation. The most accepted theory of SM 
pathogenesis is that obstruction to CSF flow 
results in a mismatch in timing between the 
arterial and CSF pulse peak pressure. If peak 
CSF pressure is high when spinal arteriole 
and perivascular space pressures are low then 
the perivascular spaces act as a one-way valve, 
drawing in CSF which collects in, then 
expands and disrupts, the spinal cord central 
canal and ultimately a syrinx develops.
• Nervous.
• Ophthalmic.GENETICS
• CM has moderately high hereditability  
(H2 = 0.37).
• Critically relevant SM-associated CM has 
high hereditability ( H2 = 0.81).
• Quantitative trait loci (QTL) study in the 
Brussels griffon identified two novel genomic 
regions associated to CM. One region 
contains a single gene, SALL-1 , involved in 
skull development.
• Genome-wide linkage studies in CKCS 
identified a haplotype, inferring protection 
against SM associated with CM.
• QTL in CKCS identified two loci on Canis 
familiaris  autosome 22 (CFA 22) and CFA 26 
associated with SM maximum transverse 
diameter linked to reduced volume of caudal 
cranial fossa:
◦ Loci on CFA22 contained a single gene, 
PCDH17 , a CNS cell adhesion molecule 
and strongest candidate gene.
◦ Loci on CFA26 contained a single gene, 
ZWINT , expression of which is associated 
with neuropathic pain.
• In some brachycephalic toy breeds, most 
notably the CKCS, prevalence of CM 
approaches 100%.
• SM prevalence increases with age with 25% 
CKCS affected at 1 year, rising to 70% of 
CKCS >6 years.
• Studies in the Brussels griffon suggest 
42–52% have SM.
• Prevalence of clinically relevant CMSM is 
difficult to determine as pain is subjective and 
difficult to measure directly.
• One study suggested 15.4% prevalence of 
clinically relevant SM in 6-year-old CKCS.
Species
• Brachycephalic toy breeds and crosses (e.g., 
cavapoo).
• CKCS, King Charles spaniel, Brussels 
griffon, affenpinscher, Yorkshire terrier, 
Maltese, Chihuahua, Pomeranian, Boston 
terrier, papillon, French bulldog, pug.
• CM but not SM is observed in the Persian 
and other brachycephalic cats.
From 6 months; however, dogs that do not 
have clinical signs at 6 years old are less likely 
to ever develop clinical signs.
No sex predisposition.
SIGNS
• CM and SM may be clinically relevant. In 
the CKCS, clinically relevant SM is associated 
with syrinx transverse width ≥4 mm.• Signs of CM-P may be intermittent and/or 
exacerbated by excitement, exercise, weather 
conditions, and time of day (night/morning).
CM-P
• Vocalization—spontaneous; on changing 
position especially when recumbent; being 
picked up; during defecation.
• Head/ear scratching/rubbing with or 
without vocalization.
• Reduced activity (walking, playing).
• Refusal to climb stairs or jump.
• Change in emotional state/behavior (timid, 
anxious, withdrawn or aggressive).
• Disrupted sleep.
• Signs suggesting head/neck pain (aversion 
to touch/grooming; abnormal head position 
when awake/asleep; facial expression 
suggesting pain; squinting/avoiding light).
SM
• Rhythmic scratching action—(phantom 
scratching) without skin contact with 
curvature of the body and neck towards foot; 
induced by rubbing a defined area of skin, 
typically on neck and/or leash walking.
CM-P
• Yelping when lifted under sternum.
• Spinal pain—thoracolumbar > cervical > 
lumbar.
• Exotropia—ventrolateral strabismus when 
gazing to the ipsilateral side.
• Thoracic limb hypermetria.
SM
• Scratching action induced by rubbing 
dermatome corresponding to spinal cord 
dorsal horn damage by syrinx.
• Cervicothoracic torticollis (shoulder 
deviated ipsilateral; head tilt contralateral to 
spinal cord dorsal horn damage by syrinx).
• Weakness—thoracic limbs > epaxial/
hypaxial muscles > pelvic limbs.
• Proprioceptive deficits—thoracic limbs > 
pelvic limbs.
CAUSES
• SM develops secondary to CSF channel 
• Degenerative—constrictive myelopathy in 
pug and screw tail breeds associated with 
arachnoid adhesions, facet hypoplasia, 
vertebral malformation, and secondary 
ligamentous hypertrophy and intervertebral 
disc disease (IVDD).
• Anomalous—CM, spinal arachnoid 
diverticulum/web.
• Neoplastic—mass causing obstruction of 
CSF channels and/or cerebellar herniation.
• Inflammatory/infectious—meningo- 
encephalomyelitis of unknown origin 
(MUO), feline infectious peritonitis,
• T raumatic—sequel of spinal cord injury 
and arachnoid adhesions.

Canine and Feline, Seventh Edition  1313
SRISK FACTORS
Brachycephalicism and miniaturization.
  DIAGNOSIS
Spinal Pain/Weakness/Ataxia
• IVDD—acute-onset, persistent localized 
pain in dogs >18 months.
• MUO—pain with rapidly progressive 
• Atlantoaxial subluxation—tetraparesis and 
pain especially on cervical flexion.
• Discospondylitis—pyrexia and neutrophilia 
at onset; pain constant.
• Degenerative myelopathy—nonpainful 
progressive pelvic limb weakness and 
proprioceptive deficit in dogs >8 years.
Skin and ear disease—generalized, tail head, 
abdominal and digital pruritus is not a feature 
of CM/SM. In CM/SM the scratching is 
localized to the head/ears (CM-P) and neck/
shoulder/sternum (SM).
Abnormal Head Position
• Rule out vestibular dysfunction due to inner 
ear, cranial nerve VIII, or intracranial disease.
• Rule out brachycephalic obstructive airway 
syndrome (BOAS) if sleeping with head 
elevated (with BOAS often wake coughing).
N/A
IMAGING
Skull and Cervical Radiographs
Limited value; can suggest CM (short 
basicranium, minuscule frontal sinus, 
flattened supraoccipital bone, close proximity 
of the atlas to the skull). In severe SM may 
have widening of cervical spinal canal and 
remodeling and scalloping of C2. Dynamic 
cervical images to assess for atlantoaxial 
CT
Useful for defining CCJ abnormalities and 
should be performed if a vertebral 
malformation is suspected and to facilitate 
planning of implanted surgical fixation.
MRI
• Aim to establish cause of SM, i.e., CM or 
other causes of CSF obstruction. Specialized 
imaging (e.g., balanced steady-state free 
precession sequences) may be required.
• Assess if radiological findings are consistent 
with neurological localization and severity, 
e.g., seizures (forebrain) cannot be attributed 
to SM (spinal cord).
CM-P
• There is no objective measure of CM-P on 
MRI. Diagnosis is suggested by appropriate historical, clinical and MRI findings and 
eliminating other causes of pain.
• MRI features—effacement/narrowed 
subarachnoid spaces (reduced definition of the 
sulci); ventriculomegaly; small, ventral olfactory 
bulbs; rostral forebrain flattening; dorsocaudal 
displacement of rostrotentorial neuroparenchyma 
contributing to hindbrain herniation; cerebellum 
invaginated under occipital lobes; flattening/
indentation of the cerebellum by the supra  - 
occipital bone/occipitoatlantal ligament. Atlas 
closer to the skull and craniospinal junction 
flexed over odontoid peg.
SM
• MRI features as for CM-P , often with more 
pronounced CCJ changes.
• Image entire spinal cord to determine 
extent of syrinx and any spinal cord tethering.
• Clinically relevant disease is more likely 
with SM width ≥4 mm (CKCS).
• “Active” syrinx indicated by a cavity which 
expands spinal cord, has asymmetrical shape 
on transverse images, and fluid signal-void 
sign (indicates turbulent flow).
• “Quiescent” syrinx indicated by a cavity 
which is elliptical on sagittal images, 
symmetrical and circular/ovoid on transverse 
images, and does not alter spinal cord outline.
CSF—to rule out MUO; however CSF 
analysis in CM/SM may reveal mild 
inflammatory changes.
• Gross—cerebellar herniation, 
ventriculomegaly, spinal cord cavitation.
• Histopathologic—dogs with clinically 
relevant SM have asymmetrical syrinx with 
altered dorsal horn structure and altered 
expression of pain-related neuropeptides, 
substance P , and calcitonin gene-related 
peptide.
  TREATMENT
• Raise food bowls.
• Avoid neck collars if phantom scratching.
• Complementary therapy, e.g., acupuncture 
may be useful.
ACTIVITY
• Exercise encouraged to within own limits.
• Grooming may be poorly tolerated.
• Hydrotherapy may improve strength if 
SM-associated weakness.
DIET
Obesity positively correlated with a reduced 
quality of life but not greater neuropathic 
pain.
Periodic exacerbations of pain common, 
requiring “top-up” medication.SURGICAL CONSIDERATIONS
• Craniocervical decompression (CCD) 
most common surgical procedure—
establishing a CSF pathway via the removal 
of majority of supraoccipital bone and dorsal 
arch of C1; may be combined with a 
durotomy, with or without patching with a 
suitable graft material and with or without 
cranioplasty.
• Successful in reducing pain and improving 
neurologic deficits in ~80% cases; ~45% cases 
have satisfactory quality of life 2 years post- 
operatively. SM persists postoperatively.
• Clinical improvement probably attributable 
to reduction in CM-P; most cases require 
additional medical management.
• Atlantoaxial stability should be assessed 
prior to CCD.
CM-P
(NSAIDs)—at data sheet dosage.
• First-line adjuvant analgesics—gabapentin 
10–20 mg/kg q12h/q8h; or pregabalin 5 mg/
kg q12h/q8h.
• Second-line (add-on) adjuvant analgesics—
topiramate 10 mg/kg q8h; or amitriptyline 
0.25–2 mg/kg q12–24h (titrate up to 
effective dose); or memantine 0.3–1 mg/kg 
twice daily (titrate up to effective dose); or 
amantadine 3–5 mg/kg q24h.
• “Top up” analgesia—acetaminophen 
10 mg/kg PRN up to q8h and/or opioids 
at data sheet dosage.
SM-Associated Phantom Scratching
Gabapentin or pregabalin as above.
SM-Associated Weakness and Postural 
Deficits
• Drugs that may reduce CSF pressure—
proton pump inhibitors (omeprazole 0.5–1.5 
mg/kg q24h); or H2-receptor antagonists 
(cimetidine 5–10 mg/kg q8h); or diuretics 
(furosemide 1–2 mg/kg q12h; acetazolamide 
4–8 mg/kg q9–12h).
• Corticosteroids—as last resort and lowest 
possible dose that controls signs, starting with 
0.5 mg/kg prednisolone or methylprednisolone 
daily; withdraw NSAIDs.
Amitriptyline should not be combined with 
drugs metabolized by cytochrome P450 2D6, 
e.g., cimetidine.
• Furosemide may activate renin-angiotensin 
aldosterone system which may be deleterious 
in dogs predisposed to myxomatous mitral 
valve disease (MVD).(continued)  Syringomyelia and Chiari-Like Malformation

1314  Blackwell’s Five-Minute Veterinary Consult  
S• Long-term acetazolamide or corticosteroids 
not recommended due to potential adverse 
effects.
CM/SM does not increase risk of anesthesia 
unless there is syringobulbia (syrinx in 
brainstem).
  FOLLOW-UP
• Periodic review of pain management and 
• Serial MRI may be useful.
• Periodic CBC/biochemistry if receiving 
Purchase from a breeder that is health 
screening and can provide appropriate health 
certificates.
PROGNOSIS
• Approximately three-quarters of CM-P/
SM-affected CKCS deteriorate on medical 
management. However, many dogs maintain 
acceptable quality of life.
• 15–20% of CM-P/SM-affected CKCS are 
euthanized.
• 25–47% of CM-P/SM-affected dogs having 
surgical management have recurrence or 
deterioration of signs within 0.2–3 years of 
surgery.  MISCELLANEOUS
CKCS have high prevalence of unrelated 
comorbidities, including BOAS, sleep 
disordered breathing, MVD, pancreatic 
disorders, biliary tree calcification, epilepsy, 
myoclonus, fly-catching behavioral disorder, 
gastroesophageal reflux, otitis media with 
effusion, deafness, macrothrombocytopenia, 
keratoconjunctivitis sicca, idiopathic facial 
nerve paresis, idiopathic vestibular disease.
Older brachycephalic toy breeds are more 
likely to have comorbidities such as MVD. 
Head and neck myoclonus is extremely 
common in older CKCS.
• Official health schemes exist in many 
countries (e.g., the British Veterinary 
Association CM/SM scheme).
• Breeding recommendations based on SM 
status and age available.
SYNONYMS
• BOCCS.
• Caudal occipital malformation syndrome.
• Syringohydromyelia.
• BOAS = brachycephalic obstructive airway 
syndrome.
• BOCCS = brachycephalic obstructive CSF 
channel syndrome.
• CCD = craniocervical decompression.• CCJ = craniocervical junction.
• CFA = Canis familiaris  autosome.
• CM = chiari-like malformation.
• CM-P = chiari-like malformation-
associated pain.
• QTL= quantitative trait loci.
• MVD = myxomatous mitral valve disease.
• MUO = meningoencephalomyelitis of 
unknown origin.
drug.
• SM = syringomyelia.
• Frequently asked questions: http://
veterinary-neurologist.co.uk/
chiari-like-malformation-and-syringomyelia/
• T reatment algorithm: http://veterinary-
neurologist.co.uk/
cmsm-treatment-algorithm/
• British Veterinary Association CM/SM 
scheme: https://www.bva.co.uk/Canine-
Health-Schemes/CM-SM-scheme/
Knowler SP , Galea GL, Rusbridge C. 
Morphogenesis of canine chiari 
malformation and secondary syringomyelia: 
disorders of cerebrospinal fluid circulation. 
Front Vet Sci 2018, 5:171.
Rusbridge C, Stringer F , Knowler SP . Clinical 
application of diagnostic imaging of 
chiari-like malformation and syringomyelia. 
Front Vet Sci 2018, 5:280.
Author  Clare RusbridgeSyringomyelia and Chiari-Like Malformation  (continued)

Canine and Feline, Seventh Edition  1315
S  BASICS
OVERVIEW
Systolic anterior motion (SAM) is paradoxical 
dynamic movement of the mitral valve 
apparatus or some of its individual 
components in an anterior direction toward 
the left ventricular outflow tract (LVOT) and 
interventricular septum during systole. When 
the chordae tendineae are the sole component 
of the valve apparatus displaced anteriorly, the 
term chordal anterior motion (CAM) is 
sometimes used.
• When SAM was first recognized it was 
believed to be specific to the setting of 
hypertrophic cardiomyopathy (HCM) 
however, it has since been identified to 
occur under any circumstances that  
alter the dynamic geometry of the left 
ventricle (LV).
• There are multiple factors that can 
contribute to the development of SAM which 
can broadly be broken down into three main 
groupings: structural abnormalities, altered 
ventricular kinetics, and altered ventricular 
geometry (see Causes).
• Clinical manifestations occur on a spectrum 
of severity ranging from clinically silent 
changes to severe dynamic LVOT obstruction 
(LVOTO).
• Significant LVOTO can result in a pressure 
overload on the LV, resulting in myocardial 
hypertrophy; if severe enough, myocardial 
ischemia and ventricular arrhythmias may 
ensue.
• Cardiac output is also reduced with severe 
LVOTO and may result in weakness or 
collapse.
Genetics
N/A, but certain underlying conditions have 
a genetic basis in certain breeds (e.g., HCM, 
subvalvular aortic stenosis [SAS]).
T rue prevalence is unknown. One study 
identified SAM in 5.8% of apparently normal 
cats, of which 91.1% had HCM.
Species
N/A, but certain breeds may be predisposed 
to certain underlying conditions (e.g.,  
SAS in Newfoundlands; HCM in Maine 
coons).
UnknownSIGNS
• Signs are often attributable to underlying 
• Weakness, lethargy, or collapse may be 
observed with severe LVOTO.
• Patients with advanced underlying cardiac 
disease may have signs of left-sided or 
right-sided congestive heart failure (CHF) 
(e.g., tachypnea, dyspnea, cough, ascites).
• Systolic murmur which may be static, 
intermittent, or labile, i.e., variable in 
intensity from moment to moment.
• Diastolic gallop sounds may be present in 
patients with underlying cardiomyopathies.
• Femoral pulse quality may be reduced in 
patients with severe LVOTO.
• Arrhythmias may be appreciated (may be a 
direct sequela of severe LVOTO or may be 
due to the underlying disease process).
Causes
SAM is a complex and dynamic condition 
that may arise from interactions of one or 
more of the following factors:
• Structural abnormalities:
 ◦Papillary muscle displacement.
 ◦Anterior and/or posterior mitral leaflet 
redundancy.
 ◦Abnormal chordae tendineae.
 ◦Bulging of the interventricular septum.
 ◦Small LV.
• Altered ventricular kinetics:
 ◦Hyperdynamic LV (generalized or 
regional).
• Altered ventricular geometry:
 ◦Reduced distance between septum and 
mitral coaptation point.
 ◦Mitral apparatus displaced anteriorly.
 ◦Decreased anterior:posterior length 
ratio.
 ◦Decreased mitro-aortic angle.
• Any condition or intervention that alters 
left ventricular geometry or loading 
• HCM.
• SAS.
• Right ventricular systolic hypertension 
(e.g., pulmonic stenosis, tetralogy of Fallot, 
pulmonary hypertension).
• Stress/excitement.
• Mitral valve dysplasia.
• Thyrotoxicosis.
• Excess catecholamines.
• Positive inotropic drugs (e.g., dobutamine).
• Surgical mitral valve repair is identified as a 
risk factor in humans.• SAM may occasionally be observed in 
completely healthy animals.
  DIAGNOSIS
• Must differentiate SAM from other causes 
of murmurs.
• It can be diagnostically challenging to 
distinguish if LVOTO due to SAM is the 
cause or the effect of myocardial hypertrophy.
N/A
N/A
IMAGING
• Paradoxical systolic motion of the anterior 
mitral leaflet/mitral apparatus toward the 
interventricular septum is identified on 2D 
and m-mode echocardiography, and is often 
best seen from right-parasternal five-chamber 
views that highlight the LVOT.
• Color-flow Doppler assessment of the 
LVOT identifies turbulent blood flow.
• The degree of LVOTO, if present, can be 
quantified via continuous-wave ± pulsed-
wave Doppler interrogation. Doppler flow 
profiles in the setting of SAM are typically 
characterized by late systolic acceleration 
through the LVOT resulting in a “scimitar-
shaped” profile.
• Mitral regurgitation is often identified; this 
is usually mild, with an eccentric jet that is 
posteriorly directed.
• Myocardial hypertrophy may be present 
(can be both a cause and an effect of SAM 
with significant LVOTO).
• Subvalvular ridge may be present in the 
LVOT of patients with SAS.
• Underfilling of the LV may be appreciated 
in some patients with SAM.
• Other echocardiographic findings, depending 
on the type and severity of underlying 
• Radiographic changes, if present, usually 
reflect the underlying cause.
• Evidence of left- or right-sided cardiomegaly ± 
CHF may be present on thoracic radiographs.
ECG
• Atrial or ventricular arrhythmias may be 
present, depending on underlying pathology.
• Evidence of left- or right-sided cardiomegaly 
may be present, depending on underlying 
cause and severity.Systolic Anterior Motion

1316  Blackwell’s Five-Minute Veterinary Consult  
S• May see evidence of myocardial ischemia 
(e.g., S-T segment elevation/depression) with 
severe LVOTO.
Gross or histopathologic findings reflect any 
underlying conditions, if present.
  TREATMENT
T reat or remove underlying cause(s)
• Only as needed to manage an underlying 
condition or CHF , if present.
• Therapy with beta-blocker drugs (e.g., 
atenolol) is controversial. Beta-blockers are 
empirically used by some clinicians to reduce 
the severity and/or the effects of SAM/LVOTO, 
however evidence of efficacy or any survival 
benefit is lacking.
• The use of positive inotropic drugs (e.g., 
dobutamine, pimobendan) in the setting of 
SAM with significant LVOTO is theoretically 
concerning and thus warrants prudence. 
Hypotension has been reported in a cat with 
SAM that received pimobendan for the 
treatment of heart failure, however a recent 
study of pimobendan administration in cats 
with HCM showed no difference in the 
incidence of LVOTO between treatment and 
placebo groups.
• Beta-blockers may reduce systolic function 
and should be used cautiously in patients 
with known systolic dysfunction.  FOLLOW-UP
Type and frequency depends on any 
underlying disease processes.
N/A
N/A
• Depends on the nature and severity of 
• In a study of cats with HCM, cats with 
SAM had longer survival times than those 
without. It is speculated that this may be due 
to SAM allowing earlier identification of the 
disease due to the presence of a murmur.
N/A
N/A
Certain underlying causes (e.g., HCM, SAS) 
may be heritable.
SYNONYMS
• Chordal anterior motion.
• CAM.
• Dynamic LVOTO.
• When LVOTO due to SAM is present 
concurrently with a HCM phenotype, the 
term hypertrophic obstructive cardio -
myopathy is used.SEE ALSO
• Aortic Stenosis.
• CAM = chordal anterior motion.
• HCM = hypertrophic cardiomyopathy.
• LVOT = left ventricular outflow tract.
• LVOTO = left ventricular outflow tract 
• SAM = systolic anterior motion.
• SAS = subvalvular aortic stenosis.
Fox P , Keene B, Lamb K, et al. International 
collaborative study to assess cardiovascular 
risk and evaluate long-term health in cats 
with preclinical hypertrophic 
cardiomyopathy and apparently cats: The 
REVEAL study. J Vet Intern Med 2018, 
32(3):930–943.
Ibrahim M, Rao C, Ashrafian H, et al. 
Modern management of systolic anterior 
motion of the mitral valve. Eur J Cardio-
Thorac Surg 2012, 41(6):1260–1270.
Levine R, Vlahakes G, Lefebvre X, et al. 
Papillary muscle displacement causes 
systolic anterior motion of the mitral valve. 
Experimental validation and insights into 
the mechanism of subaortic obstruction. 
Circulation 1995, 91(4):1189–1895.
Payne JR, Borgeat K, Connolly DJ, et al. 
Prognostic indicators in cats with 
hypertrophic cardiomyopathy. J Vet Intern 
Med 2013, 27(6):1427–1436.
Consulting Editor  Michael AherneSystolic Anterior Motion  (continued)

Canine and Feline, Seventh Edition  1317
TTapeworms (Cestodiasis)
  BASICS
OVERVIEW
• Infection of small intestine with adult 
tapeworms of T aenia  (especially T. pisiformis  
of dogs and T. taeniaeformis  of cats), 
Dipylidium caninum , Echinococcus  spp., 
Mesocestoides , Diphyllobothrium , or Spirometra .
• Infection by ingestion of intermediate host 
containing tapeworm larvae.
• Most cause no apparent harm to host other 
than perianal pruritus; Spirometra  may cause 
diarrhea, weight loss, vomiting.
• Peritoneal larval cestodiasis (PLC)—poten-
tially fatal peritoneal infection in dogs 
(accidental intermediate hosts) caused by 
Mesocestoides  larvae.
SIGNS
• Motile or dried, white to cream-colored, 
single proglottids or chains of square or 
rectangular proglottids of T aenia  and barrel-
shaped proglottids of Dipylidium  visible on 
perineum or in feces; Mesocestoides  proglottids 
are club-shaped, smaller, more numerous; 
Echinococcus  proglottids too small to see.
• Dragging or rubbing anus on ground 
(pruritus).
• Diarrhea, weight loss—possible with 
Spirometra .
• PLC—abdominal distension (ascites), 
anorexia, lethargy.
• T aenia , Echinococcus , Mesocestoides —eating 
viscera of intermediate hosts (birds, reptiles, 
rabbits, rodents, sheep).
• Dipylidium  infections—eating fleas, lice.
• Spirometra —ingesting copepods; uncooked 
amphibians, reptiles, birds, mammals.
• Diphyllobothrium —eating uncooked fish.
  DIAGNOSIS
• Anal sac disease.
• Other causes of diarrhea.
• PLC—causes of ascites.
PLC—leukocytosis, hypoalbuminemia.
N/A
IMAGING
PLC—abdominal ultrasonography, 
radiography.DIAGNOSTIC PROCEDURES
• Fecal flotation to detect eggs; false negatives 
if eggs not released from proglottids; crush 
minced segments between two glass slides to 
release eggs, add drop of water, examine 
microscopically.
• Dipylidium —press adhesive cellophane tape 
to perianal skin, then apply tape to microscope 
slide; packets contain multiple pale yellow 
eggs ~50 μm in diameter with hexacanth 
embryo with three pairs of hooks.
• T aenia , Echinococcus —individual spherical 
brown eggs ~30–35  μm in diameter with 
hexacanth embryo.
• Mesocestoides —individual oval thin-shelled 
eggs with hexacanth embryo.
• PLC—detect larvae in peritoneal fluid by 
microscopy or PCR-restriction fragment 
length polymorphism.
• Diphyllobothrium /Spirometra —individual 
eggs with operculum; contain fully developed 
coracidium.
  TREATMENT
• Outpatient anthelmintic treatment.
• Flea (or louse) control ( Dipylidium ).
• PLC—anthelmintic treatment, may require 
peritoneal lavage or surgery to remove larvae.
• Fenbendazole 50 mg/kg PO q24h for 
3 days.
• Praziquantel 5 mg/kg PO, SC once:
 ◦Resistance to praziquantel in Dipylidium  
is emerging issue.
 ◦7.5 mg/kg PO for 2 days for 
Diphyllobothrium  (dogs, extra-label).
• Praziquantel/pyrantel pamoate—label dose 
(cats).
• Praziquantel/pyrantel pamoate/febantel—
label dose (dogs).
• Epsiprantel 5.5 mg/kg PO (dogs), 2.8 mg/
kg PO (cats) for T aenia , Dipylidium ; 7.5 mg/
kg PO (dogs) for Echinococcus .
• Emodepside 3 mg/kg/praziquantel 12 mg/
kg, topically for T aenia , Dipylidium  (cats).
• Canine PLC—praziquantel 5 mg/kg SC, 
repeat in 2 weeks; fenbendazole 50–100 mg/
kg PO q24h for 4–8 weeks (extra-label; 
clinical remission, often not curative).
Do not use praziquantel or epsiprantel in 
animals <4 weeks old.  FOLLOW-UP
• Post-treatment examination for tapeworm 
segments or eggs; incompletely removed adult 
Mesocestoides  can repopulate by asexual 
multiplication.
• PLC—ultrasonography, abdominocentesis 
to detect recurrence; larvae difficult to 
eliminate (repopulate by asexual 
multiplication).
• Flea (or louse) control to prevent Dipylidium  
• Prevent hunting, scavenging, eating of 
PROGNOSIS
• Anthelmintic treatment eliminates adult 
T aenia , Echinococcus , Dipylidium ; reinfection 
often occurs.
• Incomplete removal of adult Mesocestoides  
can result in recurrence without reinfection.
• PLC treatment provides clinical remission, 
often not curative.
• Children at risk for Dipylidium  infection by 
ingestion of fleas; tapeworm segments have 
been mistaken for pinworms.
• Ingestion of Echinococcus  eggs can cause 
hydatid disease in humans.
• Strict sanitation should be practiced when 
taeniid eggs observed due to similar egg 
morphology of T aenia  and Echinococcus .
• Human infection with Mesocestoides  can 
occur by ingestion of intermediate hosts.
• Human infections can occur by ingestion 
of uncooked fish ( Diphyllobothrium ), 
copepods ( Spirometra ), or vertebrate 
• PLC = peritoneal larval cestodiasis.
Saunders, 2009, pp. 131–147, 149–151.

1318  Blackwell’s Five-Minute Veterinary Consult  
T  BASICS
OVERVIEW
• Disorders of the temporomandibular joint 
(TMJ) alter masticatory function due to 
mobility and functional changes of the joint.
• Genetic, traumatic, degenerative, or 
idiopathic causes may result in pain, occlusal 
dysfunction, joint laxity, chronic arthritis, or 
open-mouth locking.
• No breed, sex, or age predisposition in most 
TMJ disorders.
• Open-mouth mandibular locking—basset 
hounds; Irish setters.
• Genetic predisposition in certain breeds 
(e.g., basset hounds) to develop TMJ 
SIGNS
• Difficulty opening mouth.
• Difficulty closing mouth.
• Laxity or excessive lateral movement of the 
mandible.
• Pain and/or crepitation when masticating, 
yawning, and/or vocalizing.
Specific
• TMJ luxation/subluxation—history of 
trauma or mouth locked open; radiographic 
evidence of luxation.
• Open-mouth mandibular locking—
mandibular coronoid process buccal to the 
ventral surface of the zygomatic arch; locked 
in that position; large bulge palpated on 
• T raumatic injury—evidence of trauma; 
mouth dropped open; mobility of mandible 
(may have multiple fractures); radiographs 
indicate fracture.
• Osteoarthritis/chronic post-traumatic 
changes—crepitation and pain when eating 
or if mandible is forced to move; radiographs 
may show osseous reaction indicative of 
arthritic changes.
• Patients at a higher risk to experience 
injuries—young; free roaming.
• T rauma with fractures or a luxation 
resulting in immediate problems, and future 
degenerative problems.
• Mandibular neuropraxia—carrying heavy 
objects by mouth.
• Masticatory muscle myositis (MMM)—
adult; large-breed (e.g., German shepherd 
dogs).  DIAGNOSIS
• Mandibular neuropraxia—motor nerve 
branches of masticatory muscles stretched 
when carrying heavy objects; mandible hangs 
open but is easily closed.
• MMM—autoimmune disease of type 2M 
myofibers of masticatory muscles supplied by 
trigeminal nerve; trismus progresses to total 
inability to open jaws.
• Serum autoantibodies to type 2M 
myosin—to rule out MMM.
• Cytology of fluid aspirated from TMJ—
inflammation from polyarthropathy.
IMAGING
• Skull radiography—essential to perform 
proper radiographic technique to visualize the 
TMJ.
• MRI—gold standard for imaging the TMJ.
• Muscle biopsy—rule out MMM.
  TREATMENT
• Eliminating or altering the etiologic factor 
responsible for the disorder, as well as 
correcting the problem.
• TMJ luxation—traumatic: luxation often 
occurs in a rostral–dorsal direction; in acute 
cases, place a “dowel” (pencil) across the 
mouth between the carnassial teeth; gently 
close the rostral portion of the mouth with a 
gentle “push” to reduce the luxation (push 
caudally for a rostral luxation); chronic 
luxation may not reduce and may require 
surgery. Digital manipulation may also be 
immediate attention; sedate animal, open 
the mouth further and apply gentle pressure 
on the bulging coronoid process to allow it 
to slip back under the zygomatic arch; 
surgical management: excise ventral portion 
of the zygomatic arch and/or a dorsal 
portion of the coronoid process to relieve 
future locking.
• Injury or fracture at TMJ—depends on 
extent of damage; fixation is difficult; 
condylectomy sometimes necessary.• Chronic osteoarthritis or ankylosis—if 
severe, condylectomy may be needed.
• “Dropped jaw” (trigeminal [mandibular] 
neuropraxia)—conservative treatment: rest, 
• MMM—immunosuppressant medications.
• Analgesics—for painful disorders, both 
acute and long-term management.
• Anti-inflammatory drugs—for post -
operative pain and chronic inflammation.
• Muscle relaxants—help prevent increased 
muscle activity due to chronic pain response.
  FOLLOW-UP
Each case should be carefully followed 
because of the progressive changes that may 
occur in the TMJ, especially after traumatic 
injury.
Avoid situations that allow for trauma (pets 
running loose).
In many cases after surgical treatment involving 
TMJ disorders, arthritis may develop later.
Depends on the disorder afflicting the TMJ 
and the degree to which it is affected.
Avoid contraindicated medications.
SEE ALSO
Maxillary and Mandibular Fractures.
• MMM = masticatory muscle myositis.
• TMJ = temporomandibular joint.
Consulting Editor  Heidi B. LobpriseTemporomandibular Joint Disorders

Canine and Feline, Seventh Edition  1319
TTesticular Degeneration and Hypoplasia
  BASICS
OVERVIEW
• Degeneration—histologic changes 
occurring in the testes after puberty; may be 
differentiated from hypoplasia by increased 
thickness of basement membrane or by 
recognizing a space-filled gap between tail of 
epididymis and caudal pole of testicle.
• Hypoplasia—a variety of histologic lesions 
thought to be congenital (although often not 
obvious until after puberty) or heritable.
• Dog—any age or breed; hypoplasia, 
generally young; degeneration, generally old.
• Tortoiseshell cat—may be fertile; usually 
linked with sex chromosome abnormalities 
(see Sexual Development Disorders).
SIGNS
• Hypoplasia (dogs)—rarely any physical 
signs other than small testes.
• Degeneration (dogs)—history of scrotal or 
testicular insult may be relevant, reduced 
testicular size and loss of normal turgidity.
• Oligospermia (low numbers of spermatozoa 
in the ejaculate) or azoospermia (no sperma  - 
tozoa in the ejaculate).
Degeneration
• Heat.
• Irradiation.
• Arterial sclerosis.
• Epididymal occlusion.
• Incisional testicular biopsies.
• Any previous scrotal or testicular lesion may 
be related.
• Metals—lead salts, cadmium, organic 
mercurial compounds.
• Orchitis—infectious (such as brucellosis) or 
noninfectious (autoimmune).
• Some medications—cimetidine, 
ketoconazole, nitrofurans, flutamide.
• Steroid hormones—estrogen: secreted  
by a Sertoli cell tumor or exogenous  
exposure.
• Other hormonal abnormalities—hypo -
thyroidism, hypocortisolism, hyperadreno- 
Hypoplasia
• Klinefelter (XXY) syndrome.
• XX sex reversal—disorder of sexual 
development with the absence of SRY region 
(dogs).
• Hypogonadotropic hypogonadism—may 
be acquired from traumatic or neoplastic 
lesion of the pituitary.  DIAGNOSIS
• Degeneration—azoospermia or severe 
oligospermia in previously fertile dogs having 
small testes.
• Hypoplasia—azoospermia with no history 
of proven fertility in dogs with small testes.
• Spermatocele.
• Sperm granuloma.
• Orchitis.
• Ejaculatory failure—retrograde ejaculation, 
incomplete ejaculation.
Alkaline phosphatase (ALP) concentration of 
seminal plasma—rule out incomplete 
ejaculation; samples with ALP <5,000 U/L 
consistent with incomplete ejaculation or 
bilateral epididymal obstruction.
IMAGING
Ultrasonography—testicular size (document 
decreasing values over time, comparison 
between testicles); heterogenous echogenicity 
of parenchyma, with or without calcification 
(chronic).
• Semen evaluation.
• Testicular biopsy (for azoospermia)—T ru-
Cut (tissue plug): most complete histopath -
ologic diagnosis; fix tissue for sectioning in 
Bouin’s or formalin solutions.
• Karyotype—(hypoplasia) identify extra X 
chromosome or other numerical or structural 
chromosome anomaly.
• Normal spermatogenesis on biopsy—
indicates obstruction in azoospermic dogs.
• Basement membrane thickness—
differentiates hypoplasia from degeneration 
(thickness increased).
  TREATMENT
• Removal of inciting cause, if possible; 
degeneration linked to adenohypophysis, 
adrenal gland, thyroid gland, or other 
metabolic disruption.
• No specific diagnosis—may try 
gonadotropic hormones; rare anecdotal 
reports of success.
• Gonadotropin-releasing hormone (GnRH) 
therapy successful in men with hypogonado -tropic hypogonadism; no controlled studies 
in domestic animals:
◦ GnRH 1  μg/kg SC, with or with human 
chorionic gonadotropin (hCG) 1,600 IU, IM.
◦ hCG 500 IU SC, 2 times/week.
  FOLLOW-UP
Suspected testicular degeneration (dogs)—a 
repeat semen analysis performed at least 70 
days after correcting any identified underlying 
cause is needed before long-term prognosis 
can be assessed.
• Hypoplasia (dogs)—prognosis for fertility 
poor.
• Degeneration (dogs)—prognosis for 
sustained fertility depends on cause and 
duration of ejaculate quality and accuracy of 
breeding management (see Breeding, Timing).
SEE ALSO
• Spermatocele/Sperm Granuloma.
• Spermatozoal Abnormalities.
Disorders of the canine penis and prepuce. 
356–367.
McEntee K. Reproductive Pathology of 
Domestic Animals. San Diego, CA: 
Academic, 1990, pp. 262–263.

1320  Blackwell’s Five-Minute Veterinary Consult  
TTetanus
  BASICS
OVERVIEW
• Clostridium tetani —an obligate anaerobic 
spore-forming Gram-positive rod found in 
soil and as part of normal bacterial flora of 
the intestinal tract of mammals; predilection 
for contaminated necrotic anaerobic wounds.
• Germinating spores—in wounds, produce 
potent exotoxin tetanospasmin (tetanus 
toxin); resistant to disinfectants and to effects 
of environmental exposure.
Dogs, rarely cats.
SIGNS
• Signs appear days to months after spores 
enter wound.
• Wound—often necrotic; but skin may have 
healed and not visible to owner.
The most common initial  clinical signs in 
affected dogs are ocular and facial abnormalities.
Localized
• Mild rigidity of muscles or leg nearest the 
site of spore inoculation (wound).
• Stiffness of (hind) limbs; stilted gait; mild 
weakness and incoordination.
• Can resolve spontaneously—reflects partial 
immunity to tetanospasmin.
• Can be prodromal to generalized disease—
when enough toxin gains access to CNS.
Progressive/Generalized
• Tail—stretches out; progressive tetany of 
muscles to point of sawhorse appearance.
• Convulsions (clonic)—limbs; whole body 
(opisthotonus); pain during contractions.
• Dyspnea.
• Difficulty opening jaws—trismus 
(lockjaw).
• Dysphagia, dysphonia.
• Eyes—lids retract (risus sardonicus, also 
includes wrinkled forehead and grinning 
appearance); third eyelid prolapses when head 
is touched; eyeballs recede into orbit 
(enophthalmos).
• Erect ears.
• Fever, painful urination (dysuria), and 
constipation—may be seen.
• Tetanic muscle spasms—from stimulation 
(sudden movement, sound, touch).
• Death—during spasm of laryngeal and 
respiratory muscles (fatal acute asphyxia).
• Unattended wounds (e.g., puncture wounds 
with foreign body, surgical wounds, compound 
bone fractures, tooth eruptions/fractures, foot 
injury or trauma)—portal of entry for spores.• Outdoor activities provide opportunities for 
trauma/exposure.
  DIAGNOSIS
• Intoxications— strychnine, bromethalin, 
metaldehyde poisoning.
• Dystonic reaction to neuroleptic drugs 
(acepromazine, prochlorperazine).
• Rabies.
• Meningitis–encephalitis.
• Immune-mediated polymyositis.
• Spinal trauma.
• Initial leukopenia; then moderate 
leukocytosis; then return to reference  
range.
• Aspartate aminotransferase (AST) and 
creatine phosphokinase—some increased 
activity due to muscle damage (tremors).
• Urinalysis—possible myoglobinuria from 
• Venous or arterial blood gas analysis—assess 
adequacy of ventilation (P co2).
• Serology—antitetanus antibody often 
undetectable in serum.
• Culture—wounds; usually unrewarding; 
must use anaerobic transport medium (do not 
refrigerate).
• Serum—to detect toxin (by mouse 
neutralization).
• CSF and blood cultures for bacterial 
pathogens of meningitis.
  TREATMENT
• Inpatient—constant nursing care 
important; supportive care for prolonged 
period (3–4 weeks).
• Feeding—patients often have difficulty 
prehending food; gastrotomy tube may be 
necessary; force feeding may exacerbate 
tetanic state (not advised).
• Hydration—maintain with oral water; if 
inadequate give a balanced IV fluid.
• Keep patient in darkened quiet area; do not 
disturb.
• Keep patient on soft bedding; prevent 
decubital ulcers; rotate stabilized patients 
cautiously, q4–6h.
• Airway and ventilation—assess; may be 
necessary to perform endotracheal intubation; 
tracheostomy may be necessary; monitor 
blood gas for evidence of hypoventilation.  MEDICATIONS
Sedation
• To control reflex spasms and convulsions.
• Chlorpromazine 0.1–0.5 mg/kg IM, IV, 
PO q6–12h, also acepromazine 0.01–0.1 mg/
kg IV, IM, SC q6–8h; 1–3 mg/kg PO q8h.
• Benzodiazepines—may be administered 
CRI or intermittent dosing:
◦ Midazolam 0.25 mg/kg IV, IM q4–6h or 
0.2–0.5 mg/kg/h IV CRI.
◦ Diazepam 0.5–1 mg/kg PO (dog), IV, 
IM q8h or 0.1–1 mg/kg//h IV CRI.
• Phenobarbital 1–4 mg/kg PO, IV q12h.
• Propofol—may be considered if unable to 
stop tremors; endotracheal intubation 
Tetanus Antitoxin
• Binds only toxin that is free or unbound, 
does not eliminate already bound toxin.
• First test for hypersensitivity reaction 
(0.1 mL SC and observe).
• Human tetanus immunoglobulin—administer 
500–3,000 U IM at multiple sites, especially 
proximal to wound; or use equine tetanus 
antitoxin 100–1,000 U/kg IV; may also be given 
SC or IM. Maximum dose 20,000 U/kg.
• Administer adsorbed tetanus toxoid 
intramuscularly.
• Kill vegetative bacteria to reduce formation 
of additional toxin; this has no effect against 
toxin already bound to nerves.
• Metronidazole 10 mg/kg PO, IV q8–12h, 
• Penicillin G 20,000–100,000 IU/kg 
q6–12h for 10 days; use sodium/potassium 
salt (IV) on the first day and procaine 
penicillin (IM) thereafter.
• Glycopyrrolate 0.005–0.01 mg/kg IV, IM 
q4–6h can be used to treat bradycardia 
associated with severe tetanus.
• Avoid glucocorticoids and atropine.
• Use caution with narcotics—depress 
respiratory center.
• Avoid oral diazepam in cats due to 
  FOLLOW-UP
• Monitor for decubital ulcers and peripheral 
nerve palsies.
• Monitor blood pressure and ECG.
• Aspiration possible.

Canine and Feline, Seventh Edition  1321
T• Constipation possible.
• Vaccinate—tetanus toxoid; not typically 
used in dogs and cats.
• Prevent skin wound trauma—clear runs 
and yards of wire, glass, etc.
• Wound management—early and thorough 
irrigation; debridement and drainage, 
especially in tetanus-prone wounds.
• Younger dogs with tetanus may be more 
likely to develop severe clinical signs.
• The prognosis for survival in dogs with 
tetanus is good if abnormalities in heart rate 
or blood pressure values do not develop.
• Prognosis—depends on number of factors; 
poorer prognosis has been associated with more toxin bound to nerves, wounds closer to 
the head, shorter interval between injury and 
first tetanic spasm, and development of 
• Course of recovery—slow; requires 
rehabilitation to regain full use of limbs; most 
recover in 1 week; some have a course of 3–4 
weeks; unattended disease can be fatal if it 
progresses to generalized disease (vs. localized 
tetanus).
None, but tetanus spores ubiquitous in 
environment.ABBREVIATIONS
http://www.cdc.gov/vaccines/pubs/pinkbook/
tetanus.html
Burkitt JM, Sturges BK, Jandrey KE, et al. 
Risk factors associated with outcome in 
dogs with tetanus: 38 cases (1987–2005). 
J Am Vet Med Assoc 2007, 230:76–83.
Linnenbrink T, McMichael M. Tetanus: 
pathophysiology, clinical signs, diagnosis, 
and update on new treatment modalities. 
J Vet Emerg Crit Care 2006, 16:199–207.
Consulting Editor  Amie Koenig(continued)  Tetanus

1322  Blackwell’s Five-Minute Veterinary Consult  
TTetralogy of Fallot
  BASICS
OVERVIEW
• A congenital cardiac malformation that 
consists of a ventricular septal defect (VSD), 
pulmonic stenosis (PS), an overriding aorta, 
and right ventricular (RV) hypertrophy 
(Figure 1). The essential developmental 
abnormality is probably cranial deviation of 
the infundibular (outlet) septum; the other 
defects are secondary. • Hemodynamics are 
determined primarily by the size of the VSD 
(typically large, i.e., equals or exceeds area of 
the open aortic valve) and the severity of RV 
outflow tract obstruction (RVOTO). A large 
VSD allows equilibration of left and RV 
pressures, with shunt direction determined by 
the relationship between peripheral vascular 
resistance and the resistance to RV ejection. 
Severe RVOTO results in a right-to-left shunt 
with cyanosis and compensatory erythrocytosis 
as prominent clinical features. • An uncommon 
congenital defect, but the most common 
congenital cardiac malformation that causes 
cyanosis in dogs and cats.
• Dog and cat—uncommon in both. 
• English bulldog and keeshond predisposed.
SIGNS
• Weakness. • Syncope. • Shortness of breath.Physical Examination Findings
• Systolic left basilar ejection murmur, caused 
by RVOTO in most patients; some with hyper  - 
viscosity and severe pulmonary stenosis do not 
have murmurs. • Cyanosis—most patients; 
degree of cyanosis depends on the direction and 
volume of shunt. If RVOTO is mild, direction 
of the shunt may be left-to-right; in this case, 
cyanosis is absent and the pathophysiology is 
that of an isolated VSD. • Arterial pulses 
usually normal. • Congestive heart failure rare, 
possibly because the right ventricle can unload 
into the left ventricle, preventing the development 
of suprasystemic RV pressures.
Congenital; a continuum of conotruncal 
defects that includes tetralogy of Fallot 
inherited in keeshonden; the mode of trans  - 
mission likely oligogenic. Genetic factors 
probably etiologically important when tetralogy 
of Fallot observed in patients of other breeds.
  DIAGNOSIS
• Aortic stenosis, PS, VSD, and atrial septal 
defect can all cause left basilar ejection 
murmurs. • Patients with severe PS and a 
right-to-left atrial-level shunt may have 
similar findings on physical examination. 
• Other anatomic right-to-left shunts (patent 
ductus arteriosus [PDA] or VSD with high 
pulmonary vascular resistance) do not 
typically cause murmurs; differential cyanosis 
(cranial mucous membranes are pink; caudal 
mucous membranes are cyanotic) is observed 
if a PDA shunts right-to-left.
Compensatory erythrocytosis if the shunt is 
right-to-left.
IMAGING
• Variable RV enlargement. • Ascending 
aorta may be prominent. • Pulmonary vessels 
are small.
• RV hypertrophy. • Large VSD visualized 
directly. • Aortic overriding of the VSD. 
• Narrow infundibulum and/or abnormal 
pulmonic valve. • Doppler evidence of PS. 
• Contrast echocardiography typically 
delineates a right-to-left shunt.
Angiocardiography
• Reveals VSD, RV hypertrophy, PS, and 
shunt direction. • Nonselective angiography 
may confirm diagnosis in patients <10 kg.
RV hypertrophy pattern in most dogs and cats.Oximetry
Used to confirm peripheral desaturation of 
hemoglobin.
  TREATMENT
• Most treated as outpatients. • Exercise 
restriction recommended. • T reat erythrocytosis 
by periodic phlebotomy to maintain a PCV of 
62–68%. • Palliative surgical procedures that 
enhance pulmonary blood flow have been 
performed. • Definitive surgical correction 
requires cardiopulmonary bypass.
Nonselective β-adrenergic antagonists such as 
propranolol may be palliative; they act as 
negative inotropes, thereby limiting dynamic 
RVOTO, and also prevent the physiologic 
drop in peripheral vascular resistance that 
occurs during exercise. These hemodynamic 
effects serve to limit right-to-left shunting. 
Propranolol may also favorably affect the 
oxyhemoglobin dissociation curve.
Vasodilators contraindicated.
  FOLLOW-UP
• Monitor PCV every 1–3 months. • Do not 
breed affected animals. • Bacterial endo -
carditis, neurologic complications associated 
with erythrocytosis, arrhythmias, and sudden 
death are potential sequelae. • Prognosis 
generally poor; median age at death in one 
study was 23.4 months.
• PDA = patent ductus arteriosus. 
• PS = pulmonic stenosis. • RVOTO = right 
ventricular outflow tract obstruction. 
Chetboul V, Pitsch I, Tissier R, et al. 
Epidemiological, clinical, and 
echocardiographic features and survival 
times of dogs and cats with tetralogy of 
Fallot: 31 cases (2003–2014). J Am Vet 
Med Assoc 2016, 249(8): 909–917.
Consulting Editor  Michael AherneAo
LARA
LVRV
Figure 1 .
Classic tetralogy of Fallot. RA  =  right atrium, 
LA = left atrium, RV = right ventricle, LV = left ven -
tricle, Ao  =  aorta. (Source: Roberts W., Adult 
Congenital Heart Disease. Philadelphia, ©  1987 
F .A. Davis Company.)

Canine and Feline, Seventh Edition  1323
T  BASICS
Abnormal protrusion (elevation) of the third 
eyelid.
• Dogs—movement of the third eyelid is 
passive.
• Cats—partial sympathetic nervous control 
of the third eyelid.
• May be primary (conformational) or 
secondary (exophthalmos, enophthalmos, 
sympathetic denervation, painful eye).
• Nervous—autonomic nervous system.
• Ophthalmic—third eyelid(s); orbit; globe.
SIGNS
• Primary—often none; occasionally 
conjunctivitis and tearing.
• Secondary—associated with the underlying 
• Unilateral or bilateral—depending on 
cause.
CAUSES
Unilateral
Blepharospasm
• Painful ocular condition—corneal ulcer; 
glaucoma; uveitis; foreign body.
• Active retraction of the globe results in 
secondary third eyelid elevation.
• Increase in orbital volume—pushes the eye 
and third eyelid forward.
• Abscess or cellulitis—generally young 
patients; acute onset; painful on palpation.
• Neoplasm—generally older patients; 
gradual onset; frequently not painful.
• Salivary gland inflammation/mucocele—
variable age; may be secondary to trauma; 
frequently not painful (see Orbital Diseases 
(Exophthalmos, Enophthalmos, 
Strabismus)).
• Globe—recedes into the orbit, causing 
third eyelid to appear elevated.
• Unilateral—may be caused by trauma, 
orbital fat atrophy, neoplasia, and inflamm  - 
ation.
• Horner’s syndrome—clinical signs develop 
after sympathetic denervation; elevated third 
eyelid; enophthalmos; ptosis (drooping upper 
eyelid); miosis (see Horner’s Syndrome).
Microphthalmos or Phthisis Bulbi
• Small globes—cause the third eyelid to 
appear elevated.
• Microphthalmos—congenital; idiopathic or 
may be inherited in specific breeds (many reported); other intraocular abnormalities 
may be present. May result from toxin 
ingestion (griseofulvin in pregnant cats).
• Phthisis bulbi—acquired; severe damage to 
the globe (uveitis, glaucoma, or trauma); 
ciliary body fails to produce aqueous humor; 
diminished; small, fibrotic globe.
• Other
• Neoplasia of the third eyelid—slow 
growing; usually older patients. Most common: 
adenocarcinoma of the gland of the third 
eyelid; hemangioma/hemangiosarcoma, 
melanoma and squamous cell carcinoma and 
others may involve the eyelid.
• Cherry eye—see Prolapsed Gland of the 
Third Eyelid (Cherry Eye).
• Everted or scrolled cartilage of the third 
eyelid—primarily large and giant breeds; the 
T-shaped cartilage of the third eyelid is rolled 
away from the surface of the eye instead of 
conforming to the corneal surface.
• Symblepharon—post-inflammatory 
adhesions between the third eyelid and cornea 
or conjunctiva. Common in cats who had 
ocular surface inflammation before the eyelids 
opened.
• Previous injury.
• Facial nerve paralysis—patient will retract 
the globe and “flash” the third eyelid.
Bilateral
• Space-occupying lesions of both orbits.
• Usually caused by immune-mediated 
inflammatory lesions (e.g., eosinophilic 
myositis, extraocular muscle polymyositis).
Conformational
• Breed-specific—primarily large-breed dogs.
• Deep orbits and prominent third eyelids.
• Not pathologic.
• No treatment needed.
Plasmoma
• Immune-mediated thickening and hyperemia 
of the leading edge of the third eyelid due to 
infiltration of plasma cells and lymphocytes; 
follicle formation; depigmentation.
• Primarily in German shepherd dogs; other 
breeds reported.
• May be associated with chronic superficial 
keratitis (pannus).
Other
• Blepharospasm (active retraction of globe).
• Enophthalmos—caused by dehydration, 
bilateral orbital fat atrophy secondary to 
severe cachexia, and chronic masticatory 
muscle myositis.
• Haw’s syndrome (cats)—idiopathic bilateral 
elevation of the third eyelids; primarily young 
cats with history of diarrhea; ophthalmic 
examination otherwise normal; self-limiting: 
usually resolves in 3–4 weeks without treatment.
• Dysautonomia (Key-Gaskell syndrome)—
bilateral elevated third eyelids; dilated nonresponsive pupils; keratoconjunctivitis 
sicca (KCS); dry mucosal surfaces; anorexia; 
lethargy; regurgitation; megaesophagus; 
bradycardia; megacolon; distended bladder 
(see Dysautonomia (Key-Gaskell Syndrome)).
• T ranquilizers—many (e.g., acepromazine) 
cause bilateral third eyelid elevation.
• Fatigue—transient third eyelid elevation, 
especially in dogs prone to ectropion.
• Cannabis intoxication.
• Tetanus—eyelids retract; third eyelid 
prolapse; enophthalmos; secondary to 
hypertonicity of extraocular muscles (see 
Tetanus).
Rabies—reported ocular signs include 
dilated pupils; anisocoria; third eyelid 
prolapse; uveitis (see Rabies).
  DIAGNOSIS
• Most common causes of acute onset of 
unilateral condition—ocular pain (e.g., 
corneal ulcer, uveitis); orbital inflammation 
(e.g., orbital abscess, cellulitis).
• Middle-aged or older patient with 
unilateral, nonpainful condition—third 
eyelid or orbital neoplasm likely.
• All patients—must rule out a small eye 
(microphthalmos or phthisis bulbi) and 
Horner’s syndrome.
• Likely causes of bilateral condition—
systemic illness (e.g., dehydration, cachexia, 
dysautonomia); associated with conformational 
• Prolapsed gland of the third eyelid—medial 
aspect of the third eyelid swollen; the third 
eyelid itself usually normal.
• Lightly pigmented third eyelid margin—
normal conformation; may be falsely 
identified as an elevated third eyelid.
• Leukocytosis and a left shift—with orbital 
inflammatory processes.
• Blood work—generally normal despite 
differing causes.
Dysautonomia—confirmed by measuring 
urine and plasma catecholamine concen -
trations and pharmacologic testing of the 
IMAGING
• Thoracic radiography—all patients with 
Horner’s syndrome to rule out intrathoracic 
cause of sympathetic denervation, evaluate for 
• Orbital ultrasound—recommended to help 
localize suspected orbital mass and define its 
nature (e.g., solid or cystic).Third Eyelid Protrusion

1324  Blackwell’s Five-Minute Veterinary Consult  
T• CT or MRI—further define suspected or 
known orbital mass.
• Skull radiographs—rarely show signs of 
orbital disease unless lesion is very large and 
destructive.
• Thorough ophthalmic examination 
utilizing a source of magnification.
• All patients with unilateral condition—
examine both surfaces of the third eyelid and 
the conjunctival cul-de-sac carefully for a 
foreign body or symblepharon.
• Pharmacologic testing—localize lesion 
with Horner’s syndrome (see Horner’s 
• Exploratory surgery and biopsy—may be 
only means to make a definitive diagnosis for 
a suspected orbital or third eyelid mass.
Cytology
• For suspected mass lesions:
 ◦Unguided fine-needle aspiration—only if 
the mass is anterior to the equator of the eye.
 ◦Ultrasound-guided fine-needle aspiration—  
for masses posterior to the eye; help avoid 
delicate retrobulbar structures.
• Third eyelid scrapings—German shepherd 
dogs with suspected plasmoma reveal plasma 
cells and lymphocytes.
  TREATMENT
• Painful condition—remove the cause of the 
irritation (e.g., foreign body); treat the 
primary ocular condition.
• Orbital cellulitis and abscess—orbital 
drainage and systemic antibiotics.
• Orbital neoplasms—usually require wide 
surgical excision via an orbital exenteration; 
may require adjunct therapeutic modalities if 
excision is incomplete.
• Microphthalmic eyes—usually none 
required; enucleation if painful or subject to 
recurrent conjunctivitis.
• Blind traumatized eyes—enucleate if 
painful and to prevent formation of intra -
ocular sarcomas (cats).
• Horner’s syndrome—treat cause, if known 
(~50% of dogs and cats); otherwise may 
resolve without treatment in 4–12 weeks.
• Surgical removal of the entire third 
eyelid—indicated for third eyelid neoplasia; 
may require adjunct therapeutic modalities 
if the surgical margins are not free of 
neoplasm.• Radiotherapy around the eye—may result 
in severe keratitis, dry eye, and cataracts; 
discuss enucleation with the client before 
initiating treatment if eye will be in the 
radiation field.
• Orbital exenteration—may be warranted if 
the mass extends into the orbit.
• Plasmoma—usually controlled with topical 
medications; not cured; life-long therapy 
needed; topical corticosteroids (0.1% 
q6h, reduced to q24h when appears 
resolved); topical 1% cyclosporine q12h 
also effective.
• Haw’s syndrome—usually self-limiting 
without treatment.
• See Dysautonomia (Key-Gaskell 
Syndrome), tetanus, or rabies.
Topical corticosteroids—never use in patients 
with corneal ulceration.
N/A
N/A
N/A
  FOLLOW-UP
Malignant neoplasia—thoracic radiographs 
and full physical exam q3–6 months to 
monitor for metastatic disease.
• Neoplasm—extension to or involvement of 
adjacent orbital structures (e.g., eye, orbit, 
orbital sinuses, and cranial cavity) possible; 
metastasis to distant sites (usually thorax or 
liver) possible (approximately 90% are 
malignant).
• Vision loss—from the lesion itself, from 
elevation, or from treatment (e.g., radiotherapy 
and exenteration).  MISCELLANEOUS
N/A
• Middle-aged to older patients—at risk for 
neoplastic diseases of the third eyelid and orbit.
• Young patients—at risk for congenital 
abnormalities; affected by inflammatory 
conditions of the third eyelid more frequently 
than older animals.
N/A
N/A
SYNONYMS
• Elevated third eyelid.
• Haw’s syndrome (cats).
SEE ALSO
• Dysautonomia (Key-Gaskell Syndrome).
• Ectropion.
• Entropion.
• Orbital Diseases (Exophthalmos, 
• Prolapsed Gland of the Third Eyelid 
(Cherry Eye).
• Rabies.
• Tetanus.
Kern T, eds., Veterinary Ophthalmology, 
Saunders, 2018, pp. 178–185.
Sharp NH, Nash AS, Griffiths IR. Feline 
dysautonomia (the Key-Gaskell syndrome): 
a clinical and pathological study of forty 
cases. J Small Anim Pract 1985, 
25:599–615.
C. Gilger.Third Eyelid Protrusion  (continued)

Canine and Feline, Seventh Edition  1325
TThrombocytopathies
  BASICS
OVERVIEW
• Acquired or hereditary defects that affect 
platelet function, including procoagulant 
activity. Defects are in two categories: 
intrinsic and extrinsic.
• Intrinsic platelet defects originate within 
platelets; extrinsic platelet defects affect 
platelet function indirectly (e.g., von 
Willebrand disease [VWD]).
• Affected animals typically have normal 
platelet counts but have spontaneous or 
excessive bleeding; mucosal or postoperative 
bleeding are most common.
• Thrombocytopenic animals with 
concurrent thrombocytopathia will bleed 
more excessively than expected for the platelet 
count.
• Acquired defects are the most common 
thrombocytopathias in companion animals. 
They occur in all breeds and at all ages.
• Hereditary platelet function defects may be 
diagnosed at any age but commonly appear in 
young animals with the loss of deciduous 
teeth, causing excessive bleeding.
• Hereditary defects are rare disorders that 
have been described in the following breeds/
species:
 ◦VWD—Doberman pinschers, German 
shorthair pointers, many other pure and 
mixed- breed dogs.
 ◦Type I Glanzmann thrombasthenia—
otterhound and great Pyrenees dogs
 ◦Storage pool diseases—Persian cats, 
American cocker spaniels, grey collie dogs.
 ◦CalDAG-GEFI thrombocytopathia—
basset hound, spitz, and Landseer dogs.
 ◦Scott syndrome—German shepherd dog.
 ◦P2Y12  (ADP) receptor mutation—
greater Swiss mountain dog.
SIGNS
• Often mild spontaneous mucocutaneous 
bleeding (e.g., epistaxis, petechiation, gingival 
bleeding). Petechiae are not necessarily seen 
in animals with adequate circulating platelet 
number.
• Prolonged bleeding in some animals during 
or following diagnostic or surgical procedures.
• In Scott syndrome, postoperative 
hemorrhage is the most common sign.
• Bleeding diathesis can be more severe in 
acquired systemic conditions, as other 
components of coagulation can be affected as 
well.
Acquired—Drugs
(NSAIDS; e.g., aspirin) inhibit platelet 
function by preventing the formation of thromboxane A2. More selective cyclooxy -
genase 2 (COX-2) antagonists (e.g., 
meloxicam, deracoxib) have less effect on 
• Thienopyridine prodrugs (e.g. clopidogrel) 
inhibit the platelet P2Y12 ADP receptor.
• Hydroxyethyl starch (HES) solutions 
suppress platelet function in dogs in addition 
to other anticoagulant effects, but increased 
risk of bleeding is variable and prolonged 
with HES of higher molecular weight and 
higher molar substitution.
• n3 fatty acids have a mild thrombocyto -
pathic effect in dogs that is not associated 
with clinical bleeding.
• Penicillins, tetracyclines, potentiated 
sulfonamides, anesthetic/sedative agents, and 
antihistamines cause mild platelet function 
defects in humans. Adverse effects of 
carbenicillin and ticarcillin have been 
documented in dogs and have not been 
investigated in cats.
Acquired—Secondary to Systemic 
Disease
Disseminated intravascular coagulation 
(DIC), uremia, anemia, liver disease 
(cholestasis and acquired or inherited shunts), 
ehrlichiosis, leishmaniasis, heart disease, 
immune-mediated thrombocytopenia, and 
neoplastic disorders (both hematopoietic and 
nonhematopoietic neoplasms) may alter 
Hereditary
• VWD (Doberman pinschers, German 
shorthair pointers, many other breeds)—a 
deficiency (type I and III) or qualitative 
defect (type II) of von Willebrand factor 
(VWF) prevents platelet adhesion to areas of 
vascular injury.
• CalDAG-GEFI hereditary thrombo -
cytopathia (basset hound and Landseer 
dogs)—mutations in signal transduction in 
platelets, preventing platelet activation.
• Type I Glanzmann thrombasthenia 
(otterhound and great Pyrenees dogs)—
platelet defect caused by a mutation in 
glycoprotein IIb–IIIa (fibrinogen receptor) on 
the platelet surface.
• Bernard Soulier syndrome (English cocker 
spaniel)—mutation in glycoprotein IX (VWF 
receptor complex) on the platelet surface 
prevents platelet adhesion.
• Chediak-Higashi syndrome, cyclic 
hematopoiesis, and dense granule defect 
(Persian cats, grey collie dogs, and American 
cocker spaniels, respectively)—deficiency 
(Chediak-Higashi syndrome, cyclic 
hematopoiesis) or functional defect (dense 
granule defect) of delta-granules in platelets 
results in inability to activate additional 
platelets at site of vascular injury.
• Scott syndrome (German shepherd 
dog)—platelet procoagulant deficiency 
resulting in failure to externalize phospha -tidylserine, generate microparticles, and 
support effective assembly of coagulation 
complexes, caused by a TMEM16F  mutation.
• P2Y12  receptor mutation (greater Swiss 
mountain dog)—multifactorial defect; 
platelets are not activated by ADP .
  DIAGNOSIS
• Anemia, if bleeding is severe.
• Platelet counts typically normal in dogs 
with inherited thrombocytopathies, but 
thrombocytopenia seen following hemorrhage; 
bizarre and giant platelets may be seen.
• Biochemical profile—no specific changes.
• Urinalysis—hematuria.
• Platelet function testing— may be used to 
diagnose hereditary and acquired defects, and 
to monitor effects of antiplatelet drugs:
 ◦Performed in specialized laboratories; 
requires freshly collected blood samples.
 ◦Platelet function analyzer-100, -200—
sensitive to decreased platelet function, 
VWD, and anemia.
 ◦Aggregometry (light transmittance or 
impedance)—measures platelet response to 
different agonists (stimulants), using 
platelet-rich plasma or whole blood. 
Sensitive to specific drug effects (e.g., 
clopidogrel), receptor defects (e.g., ADP 
receptor).
 ◦Plateletworks—measures percent 
aggregation using whole blood platelet 
counting by routine impedance or optical 
hematology analyzers, and is available to 
some general practices.
 ◦Platelet indices (e.g., mean platelet 
volume, platelet volume distribution width, 
mean platelet component concentration)—
variables helpful in characterizing platelet 
size, shape and activation (provided with 
some optical based hematology analyzers).
• Flow cytometry—for the detection of 
surface markers (e.g., glycoproteins), such as 
the fibrinogen receptor, P-selectin, or 
phosphatidylserine. Sensitive to Scott 
syndrome, fibrinogen receptor defects. 
Remote testing (P-selectin) shows promise for 
testing drug-effect (clopidogrel).
• VWF antigen by immunoassay—in animals 
suspected of VWD.
• Coagulation tests (prothrombin time [PT], 
activated partial thromboplastin time [aPTT], 
thromboelastography) [TEG]—to eliminate 
coagulopathy as a cause of hemorrhage; aPTT 
may be prolonged in some animals with 
VWD (due to decreased factor VIII–VWF 
binding, causing decreased factor VIII 
stability).
• Blood type: for animals who will require 
blood transfusion. There is no association of

1326  Blackwell’s Five-Minute Veterinary Consult  
Tblood type with platelet function, however, 
some platelet products may contain red 
blood cells.
• Genetic testing of carrier animals.
Buccal mucosal bleeding time (BMBT)—to 
generally assess platelet function. Sensitive to 
platelet function defects and VWD, but also 
prolonged by thrombocytopenia. Measured 
using a spring-loaded lancet that makes a 
5 mm long by 1 mm deep incision in the 
buccal (dog) or oral (cat) mucosa. The 
incision is observed until bleeding stops by 
the formation of a platelet plug. Normal 
BMBTs are less than 4–5 minutes in dogs and 
less than 2–3 minutes in cats. The BMBT can 
also be affected by hematocrit and blood 
viscosity, and results can vary between 
operators.
  TREATMENT
• T ransfusion—20 mL/kg (minimum of 
10 mL/kg) platelet-rich plasma, or 1 unit/10 
kg (minimum 1 unit/30 kg) cryoprecipitate, 
or 5.5 × 1010 platelets/10 kg body weight 
given as fresh platelet concentrate (may be 
available in some areas).
 ◦DMSO-stabilized cryopreserved and 
lyophilized platelets are available in some 
countries; these products have less 
functional activity than fresh platelets but 
may be useful for correcting hemorrhage.
transfusion to correct anemia or if other 
platelet-containing products are not available. 
Fresh packed red blood cells also contain 
platelets in the sedimented pellet, and may be 
given for patients where volume overload is a 
concern.
• Cryoprecipitate—for elective surgeries in 
dogs with VWD, cryoprecipitate should be 
administered prior to the procedure and 
continued through to the postoperative period (see above).
• In animals with acquired platelet function 
disorders, treat the underlying disease process 
or withdraw the offending agent.
• Elective surgical procedures should be 
avoided or accompanied by appropriate 
transfusion products.
• Restrict activity during a bleeding episode.
• Desmopressin (DDAVP):
 ◦1 μg/kg SC, or IV diluted in 20 mL 
saline and administered over 10 minutes to 
dogs with VWD during a bleeding episode 
or in dogs with VWD requiring emergency 
surgery.
 ◦3 μg/kg SC in dogs with 
thrombocytopathia due to aspirin, liver 
disease, and a consideration in dogs with 
other thrombocytopathias.
• Antifibrinolytic agents (aminocaproic acid, 
tranexamic acid)—prevents clots from rapid 
breakdown, more commonly used to treat 
coagulopathies. The injectable preparations of 
each drug can be used topically in areas of 
bleeding (e.g., oral mucosa). Empirical data 
are lacking for dogs and cats. Both drugs are 
contraindicated in DIC, and should be used 
cautiously in cats:
 ◦Aminocaproic acid 50–100 mg/kg PO, 
IV q6h; or 100 mg/kg IV followed by 
30 mg/kg/h IV.
 ◦T ranexamic acid 20 mg/kg PO, IV q8h, 
given over 30 minutes to minimize emesis.
  FOLLOW-UP
• Take special precautions when performing 
surgical procedures on these animals. Have type-specific blood and cryoprecipitate 
available if indicated.
• Make owner aware that animals with 
hereditary platelet function defects may have 
recurring bleeding episodes. Fatal episodes are 
uncommon.
• If a hereditary defect is identified, the 
animal should not be used for breeding.
SEE ALSO
• Chediak-Higashi Syndrome.
• aPTT = activated partial thromboplastin 
time.
• BMBT = buccal mucosal bleeding time.
• DDAVP = 1-desamino-8-d-arginine 
drug.
• TEG = thromboelastography.
• VWD = von Willebrand disease.
• VWF = von Willebrand factor.
Brooks MB, Catalfamo JL. Platelet 
dysfunction. In: Bonagura JD, T wedt DC, 
eds., Kirk’s Current Veterinary Therapy 
XIV. St. Louis, MO: Elsevier, 2009, 
pp. 292–296.
Authors  Signe E. Cremer, Anthony C.G. 
Abrams-Ogg, and Annemarie T. Kristensen
acknowledge the prior contribution of Inge 
Tarnow.Thrombocytopathies  (continued)

Canine and Feline, Seventh Edition  1327
TThrombocytopenia
  BASICS
Platelet count below the reference interval, 
which varies by laboratory and methodology.
• Platelets are produced by bone marrow 
megakaryocytes and released into the blood, 
where they normally circulate for 5–10 days.
• Thrombocytopenia is caused by one or more 
of: decreased production, increased sequestration, 
utilization, or destruction of platelets.
• Thrombocytopenia may result in 
spontaneous or excessive hemorrhage.
Hemorrhage may occur into any organ system. 
Clinical hemorrhage is most commonly 
recognized in the skin (petechiae, ecchymoses) 
and from mucosal surfaces of the gastrointestinal, 
renal/urologic, and respiratory systems; less 
commonly recognized in the ophthalmic, 
nervous, and reproductive systems.
• Thrombocytopenia is a common 
hematologic abnormality.
• Severe hemorrhage due to thrombocytopenia 
is uncommon to rare.
Species
Asymptomatic thrombocytopenias may be 
present in cavalier King Charles spaniels (see 
Pseudomacrothrombocytopenia [Inherited 
Macrothrombocytopenia]), greyhounds, 
Polish ogar dogs, Akitas.
SIGNS
• Mild, moderate, and severe risk of 
spontaneous clinical hemorrhage at platelet 
counts of <25,000/ μL, <10,000/ μL, and 
<5,000/ μL, respectively. These figures are 
guidelines only because of variation in methods 
of platelet counting, imprecision of low platelet 
counts, and individual animal variation.
• Concurrent platelet function defect, von 
Willebrand disease, coagulopathy, vasculitis, 
or sepsis increases risk of hemorrhage.
• Spontaneous or excessive bleeding, 
generally from mucosal surfaces.
• Lethargy and collapse.
• Dyspnea and coughing (respiratory tract 
hemorrhage).
• Clinical signs of the primary disease.
• Petechiae and ecchymoses.• Persistent bleeding from wounds and 
venipuncture sites.
• Melena/hematochezia/hematemesis.
• Ocular hemorrhage/hyphema.
• Splenomegaly, hepatomegaly.
• Weakness, collapse.
• Dyspnea, hemoptysis, epistaxis.
• Heart murmur (anemia).
• Neurologic abnormalities.
CAUSES
• Decreased production of platelets (may 
occur alone or with other cytopenias).
• Increased sequestration of platelets 
(splenomegaly, hypothermia).
• Increased utilization of platelets (e.g., DIC).
• Increased destruction of platelets (see 
Thrombocytopenia, Primary Immune-
Mediated)—may be primary, or secondary to 
neoplasia, infectious agents, inflammation, 
drugs.
• Increased loss—volume resuscitation after 
massive bleeding.
• Potentially any noninfectious inflammation, 
e.g., vasculitis, neoplasia.
• Potentially any infection—associated 
with feline leukemia virus (FeLV), feline 
immunodeficiency virus, distemper, 
parvoviruses, Ehrlichia  spp., Anaplasma  spp., 
Rickettsia rickettsia , leptospirosis, Borrelia 
burgdorferi , histoplasmosis, Cytauxzoon felis , 
Babesia  spp., Rangelia  spp., Hepatozoon canis , 
Leishmania  spp., Theileria  spp., heartworm, 
Angiostrongylus vasorum , and Cuterebra  spp. 
(especially small dogs).
• Potentially any neoplasm.
• Large-field radiation therapy, cytotoxic drug 
therapy.
• Potentially any drug, especially sulfa-
containing drugs, estrogens, gold compounds, 
phenylbutazone, phenobarbital (dogs); 
chloramphenicol, griseofulvin, propylthiouracil, 
methimazole and carbimazole (cats).
• Toxins and venoms—crotalid envenomation, 
zinc, autumn crocus, mycotoxins, xylitol.
• Hyperthermia (heat stroke).
  DIAGNOSIS
• Measurement error due to platelet 
clumping—more likely with traumatic 
venipuncture and in cats.
• Von Willebrand disease.
• Coagulopathy—petechiae, gastrointestinal 
hemorrhage, and epistaxis unusual; 
subcutaneous swellings, intracavity 
hemorrhage may be present.
• T rauma.CBC/BIOCHEMISTRY/URINALYSIS
Confirm analyzer thrombocytopenia by 
examination of a blood smear; inspect 
feathered edge for platelet clumps; estimate 
platelet count from red cell monolayer; each 
platelet-per-oil immersion field represents 
15,000–25,000/ μL.
• Plateletcrit (analogous to hematocrit) 
reflects platelet mass; decreased with 
thrombocytopenia; normal in dogs with 
macrothrombocytopenia.
• Abnormalities on biochemistry profile and 
urinalysis reflect primary disease or effects of 
• Von Willebrand factor antigen.
• Coagulation analysis (prothrombin [PT] 
and activated partial thromboplastin [aPTT] 
times, activated clotting time): prolonged 
results increase likelihood of disseminated 
intravascular coagulation (DIC); normal PT 
rules out vitamin K antagonism.
• D-dimers—positive result increases 
likelihood of DIC or local thrombosis.
• Serologic and PCR tests for infectious 
• Fecal flotation and Baermann tests for 
parasitic larvae.
• Antiplatelet/antimegakaryocyte antibody 
tests—negative results help rule out immune-
mediated thrombocytopenia (ITP).
• Coombs’ test—positive result increases 
likelihood of concurrent immune-mediated 
IMAGING
Abdominal and thoracic radiographs, 
ultrasound, or 3D imaging can be useful in 
elucidating the underlying etiology.
Bone marrow aspirate or core biopsy—rule 
out reduced platelet production due to 
neoplasia, histoplasmosis, maturation arrest, 
bone marrow aplasia, myelofibrosis, and bone 
marrow necrosis. There is no specific finding 
that rules in or out immune-mediated 
megakaryocytic hypoplasia. Not contra -
indicated in severe thrombocytopenia.
Secondary to hemorrhage.
  TREATMENT
• T reatment of primary disorder.
• Platelet transfusion—20 mL/kg (minimum 
10 mL/kg) fresh whole blood or platelet-rich 
plasma, or 1 unit/10 kg (minimum 1 unit/30 kg) 
platelet concentrate (fresh, room-temperature 
stored, cryopreserved, or lyophilized products 
are all commercially available). While platelet

1328  Blackwell’s Five-Minute Veterinary Consult  
Tconcentrate may increase platelet count, fresh 
whole blood is unlikely to cause a change in 
platelet numbers, although the transfused 
platelets may be enough to stop critical 
bleeding. T ransfuse if critical hemorrhage is 
noted and consider prophylactic transfusion if 
platelet count <5,000–10,000/ μL, especially 
if invasive procedures are planned. T ransfusions 
may be needed q1–3 days if severe thrombo -
cytopenia persists.
transfusion to correct anemia—bleeding due 
to thrombocytopenia is worse in the presence 
of anemia.
• Do not drain hematomas unless causing a 
problem (e.g., tracheal compression).
Minimize injections. Apply extended pressure 
after IV injection/catheterization and invasive 
procedures. Avoid jugular venipuncture and 
urine acquisition by cystocentesis.
ACTIVITY
Restrict activity in animals with moderate-to-
severe thrombocytopenia.
DIET
Avoid hard foods and toys to minimize 
possibility for gingival bleeding.
Extensive perioperative transfusion may be 
needed.
• See specific chapters for treatments of 
diseases causing thrombocytopenia.
• Acepromazine and trazadone have 
negligible effects on platelet function in dogs 
and cats and may be used to sedate animals to 
reduce risk of hemorrhage associated with 
excessive activity.
• Opioids and gabapentin are preferred 
analgesic agents; if nonsteroidal anti-
inflammatory drug (NSAID) use is required, 
selective cyclooxygenase-2 inhibitors (e.g., 
deracoxib) should be used to minimize effects 
on platelet function.
• Clopidogrel.
• n3 fatty acids have a mild negative effect on 
• Heparin may aggravate hemorrhage due to 
• Corticosteroid or other immunosuppressive 
therapy may promote infection and gastro -
intestinal ulceration.POSSIBLE INTERACTIONS
• Antibiotics have negligible effects on 
platelet function in dogs and cats (see 
Thrombocytopathies).
• Gastroprotectants have negligible effects on 
• Common anesthetic agents have negligible 
effects on platelet function.
• Corticosteroids are generally considered to 
be prothrombotic.
• Thrombopoietic stimulants—
oprelvekin—50  μg/kg SC q24h for maximum 
of 2 weeks (to avoid risk of neutralizing 
antibody formation); most useful when 
thrombocytopenia caused by cytotoxic 
therapy; expensive.
• Fibrinolysis inhibitors—aminocaproic acid, 
tranexamic acid; contraindicated in DIC.
• Vincristine—0.02 mg/kg IV, once: may 
transiently increase platelet count in dogs 
with ITP; not indicated for other etiologies of 
thrombocytopenia, may cause leukopenia.
• Melatonin and 5-methoxytryptamine.
• Lithium is not recommended.
  FOLLOW-UP
• Amount of bleeding—control of clinical 
hemorrhage is most important parameter to 
monitor to judge effectiveness of treatment.
• Serial platelet counts using same method.
• Serial coagulation profiles if DIC is 
• Hemorrhagic shock.
• Uveitis.
• Neurologic abnormalities if hemorrhage in 
CNS.
• Dyspnea if hemorrhage into respiratory 
tract.
Varies with cause. If the underlying cause of 
severe thrombocytopenia cannot be treated, 
prognosis is poor.
• If thrombocytopenia is due to reduced 
platelet production, other cytopenias may be 
present.• ITP may be solitary or associated with 
other immune-mediated disorders.
Varies with cause—e.g., FeLV in younger 
cats, ITP in middle-aged dogs, neoplasia in 
older dogs.
None specifically, although some causes of 
thrombocytopenia (e,g, leptospirosis) may be 
due to a zoonosis.
SEE ALSO
• Hyphema.
• Pancytopenia.
• Petechia, Ecchymosis, Bruising.
• Pseudomacrothrombocytopenia (Inherited 
Macrothrombocytopenia).
And specific chapters for infectious 
diseases.
time.
• ITP = immune-mediated 
drug.
https://ahdc.vet.cornell.edu/sects/clinpath/
modules/coags/acqtbtp.htm
Botsch V, Küchenhoff H, Hartmann K, 
Hirschberger J. Retrospective study of 871 
dogs with thrombocytopenia. Vet Rec 2009, 
164:647–651.
Jordan HL, Grindem CB, Breitschwerdt EB. 
Thrombocytopenia in cats: a retrospective 
study of 41 cases. J Vet Intern Med 1993, 
7:261–265.
Kelley J, Sharkey LC, Christopherson PW, 
Rendahl A. Platelet count and plateletcrit in 
cavalier King Charles spaniels and grey-
hounds using the Advia 120 and 2120. Vet 
Clin Pathol 2014, 43:43–49.
Author  Anthony C.G. Abrams-Ogg
acknowledge the prior contributions of Dr. 
William J. Reagan.Thrombocytopenia  (continued)

Canine and Feline, Seventh Edition  1329
TThrombocytopenia, Primary Immune-Mediated
  BASICS
• Immune-mediated destruction of platelets 
with no identifiable cause.
• In secondary immune-mediated thrombo -
cytopenia (ITP), infectious diseases, neoplasia, 
vaccination, or drugs (e.g., sulfonamides, 
cephalosporins, phenobarbital, nonsteroidal 
anti-inflammatory drugs [NSAIDs]) trigger the 
production of antibodies.
• Antiplatelet autoantibodies result in 
premature platelet destruction by splenic 
• In secondary ITP , platelet-bound antibodies 
can be antibodies bound to platelet antigens 
altered during course of disease or antibodies 
bound to foreign antigens or immune complexes.
• Autoantibodies can be directed against 
megakaryocytes.
• Antibody-mediated impairment of platelet 
function possible.
• Nervous.
GENETICS
Autoimmunity is frequently recognized in 
particular dog breeds and is often familial, 
suggesting a genetic influence.
PREVALENCE
Approximately 6% of dogs and 3% of cats 
Species
• Dog.
• Rare in cat.
Breed and Familial Predilections
Cocker spaniel, Maltese, bearded collie, 
poodle, Old English sheepdog, Irish setter.
• Middle-aged dogs.
• Reported age range in dogs: 0.3–15 years 
(mean 5 years); in cats: 0.7–12 years (mean 6 
years).
Female dogs.
SIGNS
• Acute-onset mucosal hemorrhage.
• Chronic, low-grade blood loss.
• Lethargy, weakness, inappetence.
• Recent drug administration, vaccines, travel 
to tick-endemic area.Physical Examination Findings
• Mucosal and cutaneous petechiae/
ecchymoses.
• Melena, hematemesis, hematochezia.
• Ocular hemorrhage, hyphema.
• Neurologic signs due to CNS bleeding.
• Dyspnea if bleeding into respiratory tract.
• Prolonged hemorrhage after trauma or 
venipuncture, hematoma formation.
• Hemorrhagic shock—pale mucous 
membrane, tachycardia, weak pulses.
• Fever.
• Palpably enlarged spleen.
  DIAGNOSIS
• Severe thrombocytopenia (generally 
<20,000 platelets/ μL).
• Careful exclusion of underlying diseases or 
• Response to immunosuppressive therapy.
clumping; especially in cats.
• Pseudomacrothrombocytopenia of cavalier 
King charles and English toy spaniels, Cairn 
and Norfolk terriers.
• Decreased production—infectious diseases, 
irradiation, primary bone marrow disorders 
(myelopthisis or myelofibrosis).
• Sequestration in the spleen.
• Increased utilization or consumption:
◦ Neoplasia, disseminated intravascular 
coagulation (DIC), thrombosis, vasculitis/
vascular damage, infectious diseases.
◦ Severe hemorrhage or thrombosis 
may result in mild to moderate 
• Thrombocytopenia often severe (<20,000–
30,000/ μL), high risk of spontaneous 
bleeding.
• Blood smear examination—to confirm low 
platelet count; to identify potential causes for 
secondary ITP .
• Anemia may be present.
• Leukogram can be normal; mild to 
moderate leukocytosis in 30% of dogs.
• Concurrent neutropenia may indicate 
primary bone marrow or infectious  
disease.
• Coagulation testing generally normal; if 
abnormal consider secondary ITP , DIC.
• Chemistry results unspecific for ITP . 
Hypoproteinemia and hypoalbuminemia due 
to blood loss, hyperbilirubinemia due to 
hematoma resorption (rare), hyperglobulinemia 
may indicate underlying infectious disease (e.g., 
ehrlichiosis, leishmaniosis, feline infectious 
peritonitis [FIP]).
• Hematuria.OTHER LABORATORY TESTS
• Infectious disease testing—secondary ITP 
reported in association with anaplasmosis, 
ehrlichiosis, Rocky Mountain spotted fever, 
bartonellosis, babesiosis, leishmaniosis, 
dirofilariasis, Angiostrongylus  infection, 
distemper, infectious hepatitis, and bacterial 
infections in dogs; feline leukemia virus, feline 
immunodeficiency virus, and FIP in cats.
• Platelet-bound antibody detection—flow 
cytometric assay in specialized laboratories.
• Adjunct immunodiagnostic testing such as 
Coombs’ test or antinuclear antibody titer if 
systemic lupus erythematosus is suspected.
IMAGING
• Splenomegaly, rarely hepatomegaly.
• Radiography and ultrasonography to 
exclude other causes of thrombocytopenia 
(e.g., neoplasia) or internal bleeding.
• Bone marrow evaluation not indicated with 
response to therapy; indicated if unexplained 
cytopenias or poor treatment response.
• Number of megakaryocytes increased unless 
immune reaction targeted against 
  TREATMENT
• Uncomplicated cases with low bleeding risk 
and good owner compliance may be treated 
• Patients with severe thrombocytopenia have 
very high risk of bleeding and warrant strict 
• Management of hypovolemia with 
crystalloid solutions (colloids may impair 
platelet function).
• Packed red blood cells or whole blood to 
correct anemia.
• T ransfusion of platelet products: 10–20 mL/
kg fresh whole blood, 1 unit per 10 kg body 
weight of whole blood-derived platelet-rich 
plasma (containing approximately 8 × 1010 
platelets/L) (minimum dose of 1 unit/30 kg) 
in animals with critical hemorrhage (caution if 
risk of hypervolemia). Platelet concentrates 
(lower total volume) if available. Platelets may 
be destroyed rapidly but may protect against 
catastrophic hemorrhage. DMSO-stabilized 
and lyophilized platelet concentrates are 
• Limit IM or SC injections. Apply extended 
pressure after IV injections. Avoid cystocentesis 
and jugular venipuncture. Bone marrow 
aspiration is safe.
• Intensive nursing care in patients with 
moderate to severe hemorrhage, hypovolemia, 
CNS abnormalities.
• Avoid hard foods, chew toys.

1330  Blackwell’s Five-Minute Veterinary Consult  
TSURGICAL CONSIDERATIONS
• Splenectomy is a controversial option for 
refractory cases not responding to medical 
therapy.
• High risk of bleeding in dogs with severe 
• May need extensive peri- and intraoperative 
transfusions with red blood cells and platelets.
• Immunosuppression:
◦ Corticosteroids—methyl prednisolone 
10 mg/kg IV once or dexamethasone 
0.2–0.3 mg/kg q24h, IV until able to take 
oral medication; prednisolone or 
prednisone (dogs 1 mg/kg PO q12h; cats 
1.5–2 mg/kg PO q12h initially).
◦ Additional or long-term therapy, usually in 
combination with corticosteroid (initial 
dosages)—cyclosporine 5 mg/kg PO q12h 
(dogs), mycophenolate mofetil 8–10 mg/kg 
PO q12h (dogs/cats), can also be given in the 
acute setting at 7–10 mg/kg IV q12h, 
azathioprine 2 mg/kg PO q24h (dogs), 
leflunomide 2–3 mg/kg PO q24h (dogs), 
chlorambucil 0.1–0.2 mg/kg PO q24h (cats).
• Other acute management—vincristine 
0.02 mg/kg IV once (dogs) or human IV 
immunoglobulin (hIVIG) 0.5–1 g/kg over 
6–8h once (dogs/cats).
• Antibiotics—consider doxycycline 5 mg/kg 
PO q12h if tick-borne disease is possible.
• Gastrointestinal protectants—sucralfate 
20–50 mg/kg PO q6–8h or proton pump 
inhibitors (omeprazole 1 mg/kg PO q12h; 
pantoprazole 1 mg/kg IV/PO q12h).
• Once the platelet count is within the 
reference interval, the initial prednis(ol)one 
dose should be tapered by approximately 1/4 
to 1/5 every 2 weeks, finally switching to 
alternate-day therapy. This and other 
therapies should be tapered slowly over 
approximately 6 months if no relapse.
• Discontinue any unnecessary medications.• Corticosteroids—gastrointestinal 
ulceration; iatrogenic hyperadrenocorticism.
• Immunosuppression—predisposes to 
opportunistic infections, mycophenolate 
associated with gastrointestinal upset.
• Cytotoxic medications (azathioprine, 
mycophenolate mofetil, chlorambucil, 
vincristine)—bone marrow suppression.
• Dose tapering too rapidly after remission 
may predispose to recurrence.
  FOLLOW-UP
• Hematocrit measurements and physical 
examination as indicated in cases with severe 
• Measure platelet count daily until >50,000/ μL;  
then every few days until platelet counts 
normalize. Then every 1–3 weeks during the 
period of drug dose tapering.
• CBC and biochemistry every 2–4 weeks.
• Urinalysis every 4–6 weeks due to risk of 
Use vaccines judiciously. Role in recurrence is 
• Spontaneous bleeding in specific areas 
(CNS, lungs) can be fatal.
• Side effects of medications.
• Platelet counts will usually increase >50,000/ μL 
a few days after starting treatment.
• Vincristine or hIVIG in addition to 
prednisone led to a shorter hospital stay or 
more rapid increase to 50,000 platelets/ μL 
(median 2.5–4 days), respectively.
• Most dogs achieve normal platelet counts.
• Failure to respond to therapy should 
prompt diagnostic reconsideration.
• 5 of 19 dogs (26%) relapsed after 19–286, 
median 66 days; causes for relapse were dose 
reduction of immunosuppression, lack of 
owner compliance.
• If relapses occur, add a second immuno -
suppressive drug.• Survival to discharge in recent studies— 
84–97% (dogs); prognosis is more favorable 
with intensive therapy including blood/
platelet products if needed.
• Mortality rate in cats is 15% (2/13).
Evans syndrome describes a rare occurrence of 
immune-mediated hemolytic anemia with ITP .
SYNONYMS
• Autoimmune thrombocytopenia.
• Idiopathic/autoimmune thrombocytopenic 
purpura.
SEE ALSO
• hIVIG = human intravenous 
immunoglobulin.
• ITP = immune-mediated thrombocytopenia.
drug.
Putsche J, Kohn B. Primary immune-
mediated thrombocytopenia in 30 dogs 
(1997–2003). J Am Anim Hosp Assoc 
2008, 44:250–257.
Wondraschek C, Weingart C, Kohn B. Primary 
immune-mediated thrombocytopenia  
in cats. J Am Anim Hosp Assoc 2010, 
46:12–19.
Author  Barbara Kohn
available onlineThrombocytopenia, Primary Immune-Mediated  (continued)

Canine and Feline, Seventh Edition  1331
TThrombocytosis
  BASICS
OVERVIEW
• Platelet count above the upper limit of the 
reference interval, which varies with the 
method of individual reference laboratories 
and methodologies.
• Reference intervals may be shifted upwards 
at high altitudes.
• Platelets are produced by megakaryocytes in 
the bone marrow and circulate for approx­
imately 5–7 days. Approximately 30% of the 
circulating platelet mass resides transiently in 
the spleen and may be released suddenly with 
splenic contraction.
• Platelet production is stimulated by 
thrombopoietin (TPO).
• Thrombocytosis can be physiologic or 
reactive. Causes include physiologic 
redistribution, inflammation, and neoplasia.
• In humans, specific gene mutations have 
been associated with the development of 
essential thrombocytosis.
• Hematologic—high circulating platelet 
count may impair ordinary hemostatic 
processes (especially von Willebrand 
factor ­mediated platelet adhesion).
• Cardiovascular—thrombosis or 
hemorrhage: uncommon.
Reactive thrombocytosis is common in cats 
and dogs.
Cats and dogs.
SIGNS
Historical and physical exam findings are 
related to underlying causes associated with 
the thrombocytosis or sequelae of micro or 
macrovascular thrombosis (e.g., organ failure, 
ischemic events) or hemorrhage.
Physiologic Thrombocytosis
Occurs secondary to redistribution of 
platelets from the spleen into circulation, 
secondary to splenic contraction associated 
with stress, exercise, or excitement.
Reactive Thrombocytosis
Occurs secondary to other conditions and 
may be short ­ or longstanding. Platelet 
elevations are typically mild to moderate and 
do not generally pose a risk for thrombosis. 
Causes of reactive thrombocytosis include:
• Inflammation secondary to infection, 
immune ­mediated disease, surgery, trauma, or 
neoplasia. Inflammatory cytokines (e.g., 
interleukin ­6) stimulate TPO production, 
which stimulates platelet production. The most common inflammatory diseases resulting in 
thrombocytosis in dogs are immune ­mediated, 
gastrointestinal, and hepatobiliary in nature. In 
cats, gastrointestinal illness (involving intestinal, 
hepatobiliary and/or pancreatic diseases) is the 
most common disease category associated with 
thrombocytosis.
• Iron deficiency is a common but 
inconsistent cause of thrombocytosis.
• Recovery from thrombocytopenia (rebound 
thrombocytosis). This occurs most commonly:
⚬ Post splenectomy (thrombocytosis may 
be marked and may persist for weeks).
⚬ Following withdrawal of 
⚬ During recovery from immune ­mediated 
⚬ Following blood loss.
• Hypercortisolemia secondary to hyper­
adrenocorticism or corticosteroid administra­
tion in dogs. In cats, hyperthyroidism may be 
a cause.
• Nonhemic malignant neoplasia (paraneo­
plastic secondary to cytokines stimulating 
thrombopoiesis)—carcinoma is the most 
common neoplasm associated with 
• Epinephrine.
• Vinca  alkaloids (vincristine, vinblastine).
Hemic Neoplasia/Myeloproliferative 
Disease
• Chronic myeloproliferative diseases are 
uncommon and include essential 
• Acute megakaryocytic leukemia—>30% of 
nucleated cells in bone marrow are megakaryo­
blasts; myelofibrosis may be present, and 
neoplastic megakaryoblasts may be present in 
circulation or other organs.
• Markedly elevated platelet counts have been 
reported with essential thrombocythemia and 
acute megakaryocytic leukemia (1–5 × 106 
platelets/ μL).
Pseudothrombocytosis
An artifactual increase in machine ­based 
platelet count caused by red or white blood 
cell fragments and lipid particles associated 
with marked hyperchylomicronemia. A 
microscopic blood smear exam is required to 
properly identify this phenomenon.
  DIAGNOSIS
Measurement error (pseudothrombocytosis) 
secondary to presence of cellular fragments or 
clerical error—a microscopic blood smear 
exam should be performed to confirm 
thrombocytosis when reported.CBC/BIOCHEMISTRY/URINALYSIS
• Confirm thrombocytosis reported by a 
hematology analyzer by microscopic blood 
smear review.
• Hyperkalemia—an artifactual increase in 
serum potassium concentration can occur 
secondary to thrombocytosis due to release of 
intraplatelet potassium during clotting. 
Measurement of potassium using heparinized 
plasma is preferred to avoid this artifact.
Use to identify underlying causes of reactive 
or neoplastic thrombocytosis. A diagnosis of 
essential thrombocytosis is generally one of 
exclusion.
Bone marrow examination—aspiration and 
core biopsy may be indicated with sustained 
extreme thrombocytosis to identify morpho­
logic abnormalities that may be consistent 
with hemic neoplasia, dysplasia, or myelo ­ 
fibrosis.
  TREATMENT
N/A
• If micro ­ or macrovascular thromboembolic 
complications are suspected, antiplatelet 
agents (e.g., clopidogrel, aspirin) may be 
indicated, although their use in humans with 
thrombocytosis has been associated with more 
severe hemorrhagic complications. Consultation 
with a veterinary specialist is highly 
recommended to determine if and which 
therapy may be indicated.
• Hydroxyurea is a chemotherapy drug that is 
used for cytoreductive therapy in humans 
with essential thrombocytosis. Published 
dosage recommendations for veterinary 
species vary widely. It is generally myelo­
suppressive, however, and will affect all cell 
lines. Consultation with a veterinary specialist 
is recommended regarding the administration 
and dosage of this drug. A comprehensive 
CBC every 1–2 weeks is recommended while 
taking hydroxyurea until platelet count 
stabilizes. Regular assessment of a serum 
biochemical profile is also recommended if 
using this drug.
Caution is recommended for the use of 
hydroxyurea in patients with anemia, 
preexisting bone marrow depression, history 
of urate stones, current infection, impaired

1332  Blackwell’s Five-Minute Veterinary Consult  
Trenal function, or with previous chemother­
apy or radiation therapy.
Adverse Effects
• Gastrointestinal effects of hydroxyurea may 
include anorexia, vomiting, or diarrhea.
• Additional adverse effects include 
stomatitis, sloughing of toenails, loss of fur, 
and dysuria.
• Bone marrow supression (anemia, 
thrombocytopenia, leukopenia) and lung 
damage (pulmonary fibrosis) are the most 
serious potential adverse effects of hydroxyurea. 
Therapy should be discontinued until values 
• Life­threatening methemoglobinemia has 
been reported in cats given high dosages 
(>500 mg) of hydroxyurea.
• Concurrent use of hydroxyurea with other 
bone marrow depressant drugs may cause 
additive myelosuppression; use with caution.• Hydroxyurea is a chemotherapy drug and a 
teratogen and contact may be hazardous to 
other animals and people that come in direct 
contact with it.
  FOLLOW-UP
Serial monitoring of comprehensive CBC for 
reassessment of thrombocytosis.
• TPO = thrombopoietin.
• www.eclinpath.com
• www.merckmanuals.com Suggested Reading
Neel JA, Snyder L, Grindem CB. 
Thrombocytosis: a retrospective study of 
165 dogs. Vet Clin Pathol. 
2012;41(2):216–22.
Rizzo F , Tappin SW, Tasker S. 
Thrombocytosis in cats: a retrospective 
study of 51 cases (2000–2005). J Feline 
Med Surg 2007, 9(4):319–325.
Woolcock AD, Keenan A, Cheung C, 
et al. Thrombocytosis in 715 dogs 
(2011–2015). J Vet Intern Med 2017, 
31(6):1691–1699.
Author  Jaime L. Tarigo
Consulting Editor  Melinda S. CamusThrombocytosis  (continued)

Canine and Feline, Seventh Edition  1333
TThunderstorm and Noise Phobias
  BASICS
Thunderstorm phobia is a disorder in which 
there is persistent and exaggerated fear of 
storms or the stimuli associated with storms. 
Fears of noises other than thunder also occur, 
such as fireworks or gunshots.
Pathophysiology involves physiologic, 
emotional, and behavioral components. 
Overactivation of noradrenergic activity in 
the locus ceruleus is likely to be involved.
• Behavioral—avoidance or escape attempts, 
pacing, freezing, contact-seeking, 
• Endocrine/metabolic—increased cortisol 
levels, stress-induced hyperglycemia.
• Gastrointestinal (GI)—inappetence, GI 
upset, hypersalivation.
• Musculoskeletal—self-induced trauma.
• Nervous—trembling, adrenergic/noradren-
ergic overstimulation.
• Skin—self-directed or accidental trauma, 
displacement grooming.
GENETICS
Familial patterns have been observed in dogs 
with noise phobias but the exact mechanisms 
of inheritance have not been established.
Fear responses to noises affect 23–50% of the 
canine population with storms, fireworks, 
vacuum cleaners and gunshots most 
commonly reported.
• Occurs in dogs and cats but dogs more 
often presented for treatment. Cats with noise 
aversion might present with redirected 
• No association with sex or neuter status.
• Any breed can be affected. In one study, 
thunderstorm phobias were most prevalent in 
herding breeds.
• Dogs may begin exhibiting signs as puppies 
but may not be presented until adulthood.
SIGNS
• One or more of the following occurs during 
storms, or when exposed to the eliciting 
noise: panting, pacing, trembling, remaining 
near owner, hiding, salivating, destructiveness, 
vocalization, self-inflicted trauma, escape 
attempts and inappropriate elimination.
• Stimuli that can elicit fear during storms 
include rain, lightning, thunder, wind, and 
possibly static electricity and changes in 
barometric pressure.Physical Examination Findings
Unremarkable, except self-inflicted or 
escape-related injuries.
CAUSES
May include combinations of the following:
• Lack of exposure to storms or noises early 
in development.
• Highly aversive experience, such as 
exposure to a violent storm.
• Genetic predisposition for emotional 
  DIAGNOSIS
• Conditions causing similar behavioral 
responses include separation anxiety, barrier 
frustration, and other phobias.
• Medical conditions that present with similar 
signs include metabolic, cardiac, neurological, 
dermatologic, GI, or any condition that causes 
significant discomfort or pain.
Results should be within normal ranges.
Tests for thyroid or adrenal disease may be 
IMAGING
N/A except if indicated to rule out medical 
cause (e.g., pain).
• N/A except to rule out medical cause.
• Electrocardiogram prior to tricyclic 
antidepressant use if suspected cardiac 
conduction abnormalities.
  TREATMENT
Outpatient treatment. Supervision may be 
necessary to prevent self-injury and destruc-
tive behavior.
Wound care for self-trauma or any physical 
trauma sustained during escape attempts.
ACTIVITY
Avoid crate confinement if not comfortably 
adapted or if risk of injury.
Behavior Management
Minimize, mute, or avoid exposure to 
stimuli by:
• Housing to a room or confinement area 
where the pet is comfortable and settled 
including safe haven confinement training to 
prevent, reduce, or mute stimuli.
• Avoid crate confinement if risk of injury or 
increased anxiety.• Stimuli might be masked or muted with 
window shutters, sound baffling, white noise, 
fan, music or products such as ear covers 
(e.g., Mutt Muffs, headphones) or eye covers 
(ThunderCap, Doggles).
• Distraction from stimuli with favored toys, 
play, or highly valued rewards.
• T raining and behavior modification to help 
calm the pet and change the association with 
the stimulus from one that is negative to 
one that is positive. Any confrontation, 
corrections or punishment in training must 
be avoided as it will further add to fear, 
anxiety and negative associations with the 
stimulus.
• Desensitization involves exposure to a 
recording of the stimulus or the stimulus 
muted or at sufficient distance that the volume 
does not elicit fear. The volume is gradually 
increased only if the pet remains relaxed.
• Counterconditioning is the pairing 
(association) of a positive outcome with each 
exposure to the stimulus. Operant counter-
conditioning involves teaching a response (sit, 
relax) that is incompatible with the fear 
response (e.g., go to bed/mat, sit/focus, or 
touch). Favored food rewards are often used 
to facilitate learning.
• Audio recordings of noises or storms are 
commercially available. Other noises or sounds 
might be reproduced for desensitization and 
counterconditioning (e.g., gunshots, vacuum 
cleaners, traffic noise) by controlling exposure 
with distance, location, or with sound muting/
baffling.
• Improper use of these exercises can worsen 
• Exercises will be ineffective if the animal 
does not react to recorded thunderstorm 
sounds.
• With the exception of dexmedetomidine 
oromucosal gel, use of medications is 
considered extra-label. Imepetoin is also 
approved for use for noise aversion but not 
yet available.
• Azapirones, tricyclic antidepressants 
inhibitors (SSRIs) require 2–4 weeks for 
effect and must be given daily during storm 
season to control anxiety. They can be used 
in combination with faster acting 
Medications for Acute, Short-Term 
Control of Anxiety
Alpha-2 Adrenergic Agonists
• Dexmedetomidine oromucosal gel—dogs, 
125 μg/m2 onto oral mucosa PRN, can repeat

1334  Blackwell’s Five-Minute Veterinary Consult  
Tdosing up to q2–3h up to 5 times per noise 
event.
• Clonidine—dogs, 0.01–0.05 mg/kg PO 
q6–24h PRN.
• Alprazolam—dogs, 0.02–0.1 mg/kg PO 
q4–12h PRN.
• Clonazepam—dogs, 0.05–0.25 mg/kg 
q8–12h PRN.
• Diazepam—dogs, 0.5–2 mg/kg PO q4–12h 
PRN.
• Lorazepam—dogs, 0.02–0.2 mg/kg PO 
q8–24h PRN.
Serotonin-2 Antagonist Reuptake Inhibitors 
(SARIs)
• T razodone—dogs, 5–10 mg/kg PO PRN to 
q8–12h.
GABA Agonists
• Gabapentin—dogs, 20–30 mg/kg PO PRN 
to q12h; cats, 10–30 mg/kg PO PRN q24h.
• Imepitoin —partial GABA agonist—dogs, 
20–30 mg/kg twice daily (begin up to 2 days 
in advance) .
Phenothiazine Tranquilizers
• Acepromazine—dogs, 0.1–1 mg/kg PO 
q6–8h.
• Poor antianxiety properties.
• Use only for  further sedation in conjunction 
with anxiolytic if needed to prevent injury.
Medications Used Daily or Throughout 
Thunderstorm Season
SSRIs
• Fluoxetine—dogs, 0.5–2 mg/kg PO q24h; 
cats, 0.5–1 mg/kg PO q24h.
• Paroxetine—dogs, 0.5–2 mg/kg PO q12h; 
• Side effects—inappetence and irritability.
TCAs
• Clomipramine—dogs, 1–3 mg/kg PO 
q12h; cats, 2.5–5 mg/cat PO q24h.
• Side effects—sedation, GI, and anticholin-
ergic effects, and cardiac conduction 
disturbances.GABA Agonists
Gabapentin—dogs 10–20 mg/kg PO q12h; 
cats, 5–10 mg/kg PO q12h.
• Avoid using TCAs and phenothiazines in 
breeding males, patients with seizure 
disorders, cardiac disease, diabetes mellitus, 
glaucoma, or thyroid disease.
• Use benzodiazepines with caution in cats 
due to risk of hepatic necrosis.
• Use benzodiazepines with caution in 
aggressive dogs—disinhibition of aggression 
possible.
• Decrease dose or avoid use of these 
medications in geriatric patients and patients 
with impaired hepatic or renal function.
• TCAs, SSRIs, SARIs, and phenothiazines 
should never be combined with monoamine 
oxidase inhibitors.
For adjunctive therapy in combination with 
drugs, environmental management and 
counterconditioning, natural therapeutic 
options that may aid in reducing anxiety 
including l-theanine alone or in combination 
with product containing whey protein, and 
Phellodendron amurense  and Magnolia 
officinalis , alpha-casozepine alone or in diets 
combined with l-tryptophan, melatonin. 
Also for cats: feline F3 facial pheromone. Also 
for dogs: dog appeasing pheromone, 
Souroubea  and Plantanus , a calming probiotic, 
aromatherapy (e.g., with lavender), pressure 
wraps or the Calmz anxiety relief system.
  FOLLOW-UP
With medication use, CBC and biochemistry 
profiles should be monitored periodically.PREVENTION/AVOIDANCE
Puppies and kittens should be exposed to a 
variety of stimuli under benign conditions, 
including puppy and kitten classes.
Severe injuries and property damage.
Prognosis depends on severity, duration, and 
the ability to prevent injuries. The condition 
can progress if left untreated.
SEE ALSO
Fears, Phobias, and Anxieties—Dogs.
• SARI = serotonin-2 antagonist reuptake 
• SSRI = selective serotonin reuptake 
• TCA = tricyclic antidepressant.
Blackwell EJ, Bradshaw JWS, Casey RA. Fear 
responses to noises in domestic dogs: 
prevalence, risk factors and co-occurrence 
with other fear related behaviour. Appl 
Anim Behav Sci 2013, 145:15–25.
Horwitz D, ed., Blackwell’s 5 Minute Consult 
Behavior, 2nd ed. Ames, IA: John Wiley & 
Sons, 2018, pp. 308–320 and 375–388.
Author  Lynne M. Seibert
Consulting Editor  Gary M. LandsbergThunderstorm and Noise Phobias  (continued)

Canine and Feline, Seventh Edition  1335
TThymoma
  BASICS
OVERVIEW
• Originates from thymic epithelium, rarely 
metastasizes.
• Infiltrated with mature lymphocytes.
• May be associated with paraneoplastic 
syndromes (myasthenia gravis, hypercalcemia 
of malignancy).
• Classified as invasive (malignant) or 
noninvasive (benign).
• Rare in dog and cat.
• Most common in medium- and large-breed 
dogs (especially Labrador and golden 
• Dogs—mean age 9.5 years.
• Cats—mean age 10 years.
SIGNS
• From physical presence of tumor—
coughing, tachypnea, dyspnea.
• Secondary to obstruction of cranial vena 
cava—swelling of the head, neck, or forelimbs 
(dependent edema).
• Paraneoplastic syndromes (hypercalcemia or 
immune-mediated disease).
• Muscle weakness and megaesophagus 
caused by myasthenia gravis ( ~20%), 
hypercalcemia (causing polyuria/polydipsia), 
polymyositis, skin disease (especially in cats: 
exfoliative dermatitis and pemphigus 
vulgaris), hypergammaglobulinemia.
• Myasthenia gravis most often pre-op in 
dogs but can develop post-op in cats.
N/A
  DIAGNOSIS
• Lymphoma (main rule-out).
• Branchial cyst.
• Ectopic thyroid carcinoma.
• Various subtypes of sarcoma.
• Mesothelioma.
• Non-neoplastic granuloma, abscess, or cyst.
• Lymphocytosis—occasionally (<5%).
• Intermittent basophilia—one case report.
• Hypercalcemia ~30%.
• Antibody titers to acetylcholine receptors to 
confirm myasthenia gravis.
• Ultrasound-guided fine-needle aspiration 
and cytology of the mass—characterized by small lymphocytes, scattered mast cells, often 
with plasma cells and up to 60% will have an 
epithelial population (vs. a pure population of 
lymphoblasts with lymphoma). Thymomas 
can be cavitated/cystic, whereas lymphoma is 
usually homogeneous upon sonographic 
• Biopsy may be needed to confirm diagnosis 
and immunohistochemical stains (cytokera-
tin, lymphocyte CD markers) can be used.
• Flow cytometry of mass aspirate can 
confirm as a minimally invasive test (usually 
polyclonal CD4+ and CD8+ whereas 
lymphoma usually not); consider PCR for 
antigen receptor rearrangements to rule out 
lymphoma.
IMAGING
• Thoracic radiography—typically reveals a 
cranial mediastinal mass with dorsal deviation 
of the trachea, and may show pleural effusion 
or megaesophagus.
• CT scan or MRI can be used prior to 
thoracotomy for surgical planning, though 
cannot predict ease of resection.
Tensilon test—evaluate for myasthenia gravis 
in patients with signs of muscle weakness, 
dysphagia, or regurgitation.
  TREATMENT
• Inpatient.
• Surgical excision—treatment of choice, and 
possible in 70% of cases; use an intercostal 
approach for small masses and a sternotomy 
for large masses. Recurrence ~17%, median 
survival time 635 days overall not considering 
prognostic factors (compared to 76 days 
without surgery).
• Dogs with myasthenia gravis and aspiration 
pneumonia have a poorer prognosis with 
surgery. Myasthenia gravis and megaesopha-
gus are not necessarily poor prognostic 
factors, but require more intensive husbandry 
practices.
• Radiotherapy—potentially beneficial by 
reducing the lymphoid component of the 
mass (50-75% of cases benefit); median 
survival time 248 days in dogs (though 75% 
alive at 1 year in one series) and 720 days in 
cats. Can be used after surgery if excision 
incomplete.
• Prednisone 20 mg/m2 PO q48h and 
cyclophosphamide 50–100 mg/m2 PO q48h—used in a very limited number of 
patients, two of which had a partial remission 
likely associated with lymphodepleting 
effects.
• Myasthenia gravis—treat with prednisone 
and anticholinesterase drugs until the tumor 
can be removed.
Immunosuppressive drugs—do not use to 
treat myasthenia gravis if aspiration pneumo-
nia present.
  FOLLOW-UP
• Thoracic radiography—every 3 months; 
monitor for recurrence.
• Cure—possible if tumor is surgically 
resectable; greater than 80% alive at 1 year if 
resectable and no associated megaesophagus; 
median survival >1800 days for cats and 800 
to >1000 days for dogs; 10–20% recur and 
may respond favorably to a second surgery.
• Prognosis—stage affects outcome after 
surgery: if invading adjacent organs, 
disseminated in thorax, or metastatic, then 
guarded (median 224 days). Prolonged 
survival despite no/minimal therapy might 
result from the indolent nature of the tumor.
• Patients with high lymphocyte proportion 
in tumor have a more favorable prognosis.
Concurrent nonthymic tumors (27%), 
polymyositis, and other autoimmune 
diseases— variable, from less than 10% and 
up to 40% of patients.
SEE ALSO
Myasthenia Gravis.
Robat CS, Cesario L, Gaeta R, et al. Clinical 
features, treatment options, and outcome in 
dogs with thymoma: 116 cases (1999–
2010). J Am Vet Med Assoc 2013, 
243:1448–1454.
Zitz JC, Birchard SJ, Couto GC, et al. Results 
of excision of thymoma in cats and dogs: 20 
cases (1984–2005). J Am Vet Med Assoc 
2008, 232(8):1186–1192.

1336  Blackwell’s Five-Minute Veterinary Consult  
TTick Bite Paralysis
  BASICS
Flaccid, lower motor neuron tetraparesis to 
tetraplegia caused by salivary neurotoxins 
from certain species of female tick.
• Presynaptic disorder—tick injects salivary 
neurotoxin that interferes with the depolariza-
tion/acetylcholine release from the presynap-
tic nerve terminal of the neuromuscular 
junction; this effect is probably associated 
with an interruption of the calcium flux 
across axonal membranes.
• Australian Ixodes holocyclus  tick—neuro-
toxin (holocyclotoxin) effects are more 
pronounced at higher temperatures; one adult 
tick is sufficient to cause neurologic signs, but 
infestation with I. holocyclus  larvae or nymphs 
can also induce signs; holocyclotoxin also 
interferes with acetylcholine release at the 
autonomic nerve terminals.
• Signs—5–9 days after initial tick 
attachment.
• Not all infested animals develop tick 
paralysis; not all adult female ticks produce 
the toxin.
• Nervous—peripheral nervous system and 
neuromuscular junction most affected; cranial 
nerves can become involved, including the 
vagus and facial nerves with the North 
American ticks and, in addition, the trigeminal 
nerves and sympathetic nervous system with 
the Australian Ixodes  tick.
• Respiratory—may see paralysis of the 
intercostal muscles and diaphragm; caudal 
brainstem respiratory center may be affected 
(rare with North American ticks; more 
common with Australian Ixodes  ticks).
GENETICS
• North America—somewhat seasonal (more 
prevalent in the summer months); in the 
warmer areas (southern United States) may 
become a year-round problem.
• Australia—distinctly seasonal, up to 75% 
of cases occur during southern hemisphere 
spring season (September–November).
• Overall incidence—low in the United 
States; higher in Australia.
• United States— Dermacentor variabilis : wide 
distribution over the eastern two-thirds of the 
country, California, and Oregon; D. andersoni : 
from the Cascades to the Rocky Mountains; 
Amblyomma americanum : from Texas and 
Missouri to the Atlantic Coast; A. maculatum : 
Atlantic and Gulf of Mexico seaboards.• Australia— I. holocyclus : coastal areas of the 
east; I. cornuatus,  southern Australia 
(Tasmania).
• Other—cases with apparent tick paralysis 
have been described in South Africa 
(Rhipicentor nuttalli ), southern Italy 
(Rhipicephalus sanguineus ), and Iran 
(Ornithodorus lahorensis ).
Species
• Australia—dogs and cats.
• United States—dogs; cats appear to be 
resistant.
None
Any age.
N/A
SIGNS
• Patient exposed to ticks (wooded area) 
approximately 1 week before onset of signs.
• Onset—gradual; starts with weakness in the 
pelvic limbs, progresses to the thoracic limbs 
within 12–72 hours.
North American Ticks
• Neurologic signs—rapidly ascending, 
flaccid generalized lower motor neuron 
tetraparesis to tetraplegia.
• Patient becomes extremely weak to 
recumbent in 1–3 days, with hyporeflexia to 
areflexia and hypotonia to atonia.
• Pain sensation preserved, no hyperesthesia.
• Cranial nerve dysfunction—uncommon; may 
note facial weakness and reduced jaw tone; 
sometimes dysphonia and dysphagia early in the 
course; megaesophagus uncommon.
• Urination and defecation usually normal.
• No cardiovascular effects.
• Respiratory paralysis—uncommon in the 
United States; may occur if ticks are not 
removed; death may occur in 1–5 days.
Australian Ticks
• Neurologic signs—much more severe and 
rapidly progressive; ascending motor weakness 
can progress to tetraplegia within a few hours.
• Sialosis, depressed gag reflex, dysphonia, 
megaesophagus, vomiting/regurgitation.
• Sympathetic nervous system—mydriatic 
and poorly responsive pupils (common in 
cats); hypertension; tachyarrhythmias; 
• Urinary bladder dysfunction may be 
present.
• Caudal medullary respiratory center 
involvement—progressive reduction in 
respiratory rate and increased respiratory 
effort.• Respiratory muscle paralysis—much more 
prevalent; dogs and cats progress to dyspnea, 
cyanosis, and respiratory paralysis within 
1–2 days if not treated.
CAUSES
United States
• D. variabilis —common wood tick.
• D. andersoni —Rocky Mountain wood tick.
• A. americanum —lone star tick.
• A. maculatum —Gulf Coast tick.
Australia
• I. holocyclus —far more potent neurotoxin 
than that of the North American species.
• I. cornuatus —southern paralysis tick, occasionally 
causes paralysis in southern Australia.
• Environments that harbor ticks.
• Australia—higher risk during spring, and in 
areas with higher rainfall, containing tree 
cover and areas of water; higher risk of death 
if dog <6 months old or a toy breed.
  DIAGNOSIS
• Acute polyneuropathy.
• Acute polyradiculoneuritis (coonhound 
• Distal denervating disease.
• Fulminant myasthenia gravis.
• Generalized (diffuse) or multifocal myelo- 
pathy.
• Intoxications (coral snake, black widow 
spider, lasalocid, blue and green algae).
Normal
Arterial blood gases—severely affected 
patients may show hypoventilation and 
respiratory acidosis (low Pao2, high Paco2, 
low pH).
IMAGING
Thoracic radiography ( Ixodes  ticks)—megae-
sophagus, aspiration pneumonia, pulmonary 
edema.
• History of exposure to ticks.
• Thoroughly search for a tick—head, neck, 
body and limbs, ear canals, mouth, rectum, 
vagina, prepuce, and in between the digits 
and footpads; clipping the entire fur may be 
needed; immediately remove tick.
• In some cases the offending tick may have 
dropped, a negative finding does not exclude 
tick paralysis.
• Electrodiagnostics—electromyogram; 
normal insertional activity without spontaneous 
myofiber activity; lack of motor unit action

Canine and Feline, Seventh Edition  1337
Tpotentials; motor nerve stimulation shows a 
dramatic decrease in amplitude or a complete 
absence of compound muscle action potentials; 
decrease in motor nerve conduction velocities; 
normal sensory conduction and repetitive 
nerve stimulation.
Pulmonary histopathologic findings in dead/
euthanized dogs include diffuse broncho-
pneumonia, congestion, and alveolar edema.
  TREATMENT
• Inpatient—neurologic dysfunction 
suggesting tick paralysis; hospitalize until 
either a tick is found and removed or 
appropriate treatment to kill a hidden tick is 
• Remove tick with forceps, applying steady 
pressure, taking care to remove mouth parts.
• Inpatient supportive care—essential until 
patient begins to show signs of recovery.
• Oxygen cage—hypoventilation ( Paco2 
<45 mmHg) and hypoxia.
• Mechanical ventilation—respiratory failure 
(Paco2 >45 mmHg).
• IV fluid therapy—if patient unable to eat/
drink due to dysphagia, vomiting/regurgi- 
tation.
• Prevention of aspiration pneumonia—elevated 
feedings if megaesophagus present.
ACTIVITY
• Keep patient in a quiet environment.
• Ixodes  tick paralysis—keep patient in a cool, 
air-conditioned area (toxin is temperature 
sensitive).
DIET
Withhold food and water if patient has 
dysphagia or vomiting/regurgitation.
• Non-Ixodes  tick—inform client that good 
nursing care is essential, although the patient’s 
recovery is rapid (within 24–72 hours) after 
removal of ticks.
• Ixodes  tick—warn client that cranial nerve 
signs and weakness often continue to worsen 
for 24–48 hours even after tick removal; 
inform client that aggressive treatment to 
neutralize the toxin must be undertaken, and 
that patient death may ensue even if 
appropriate therapy is initiated.  MEDICATIONS
• United States—if the tick cannot be found, 
topically apply a systemic insecticide such as 
fipronil or, alternatively, dip the patient in an 
insecticidal bath; often the only treatment 
needed.
• Australia—in addition to tick removal and 
use of topical acaricides, treatment often 
includes the use of commercially available 
tick antitoxin hyperimmune serum (TAS) to 
neutralize circulating toxin (0.5–1 mg/kg 
IV), depending on severity of clinical signs; 
adverse reactions to TAS administration can 
be reduced by premedication with atropine; 
if severe sympathetic signs, use of phenoxy -
benzamine, an α-adrenergic antagonist 
(1 mg/kg IV diluted in saline and given 
slowly over 20 minutes) can be beneficial.
Drugs that interfere with neuromuscular 
transmission (e.g., tetracycline, aminoglyco-
sides, procaine penicillin).
Ixodes  tick—administer IV fluids at a slow 
rate to avoid further complications of 
N/A
N/A
  FOLLOW-UP
• Non-Ixodes  tick—reassess neurologic status 
daily after tick removal; should see rapid 
improvement in muscle strength.
• Ixodes  tick—monitor neurologic status, 
respiratory and cardiovascular functions 
intensively even after tick removal, because of 
the residual effect of neurotoxin.
• Vigilantly check for ticks up to 5–9 days 
• Frequent search for ticks in endemic areas 
during spring/summer months.
• Routine topical application of acaricidal 
solution/collar, or weekly insecticidal baths.
• Short-term acquired immunity develops 
after exposure to Ixodes  neurotoxin.
No long-term complications if the patient 
survives the acute effects of the toxin.EXPECTED COURSE AND PROGNOSIS
• Non-Ixodes  tick—prognosis good to excellent 
if ticks are removed; recovery in 1–3 days.
• Ixodes  tick—prognosis often guarded; 
recovery prolonged; removal of tick does not 
always result in improvement; respiratory 
paralysis main cause of death; death in 1–2 
days without treatment; 5% mortality rate 
reported in affected dogs, fatality rate in 
affected cats appears lower.
N/A
N/A
Although humans can acquire the disease by 
being bitten by the same ticks (especially in 
Australia), tick paralysis is not transmitted to 
humans from affected pets.
Unknown
SEE ALSO
Polyradiculoneuritis).
• Polyneuropathies (Peripheral 
Neuropathies).
Añor S. Acute lower motor neuron 
tetraparesis. Vet Clin North Am Small 
Anim Pract 2014, 44:1201–1222.
Atwell RB, Campbell FE, Evans EA. 
Prospective survey of tick paralysis in dogs. 
Aust Vet J 2001, 79:412–418.
Eppleston KR, Kelman M, Ward MP . 
Distribution, seasonality and risk factors for 
tick paralysis in Australian dogs and cats. 
Vet Parasitol 2013, 196:460–468.
Malik R, Farrow BRH. Tick paralysis in 
North America and Australia. Vet Clin 
North Am Small Anim Pract 1991, 
21:157–171.
Webster RA, Mills PC, Morton JM. 
Indications, durations and outcomes of 
mechanical ventilation in dogs and cats with 
tick paralysis caused by Ixodes holocyclus : 61 
cases (2008–2011). Aust Vet J 2013, 
91:233–239.
Author  Paula Martin Vaquero
available online(continued)  Tick Bite Paralysis

1338  Blackwell’s Five-Minute Veterinary Consult  
TTicks and Tick Control
  BASICS
• Arachnids, arthropod ectoparasites feed on 
the blood of their hosts.
• Most ticks are not host specific; divided 
into argasid (soft) and ixodid (hard) ticks.
• Argasid are more primitive, more commonly 
parasitize birds; one of importance in dogs 
and cats is spinous ear tick ( Otobius megnini ).
• Ixodid ticks are more specialized and highly 
parasitic, both sexes are bloodsuckers; 
Rhipicephalus sanguineus  and Dermacentor 
variabilis  are common in dogs and cats.
• Blood-loss anemia—from heavy infestations.
• Damage to the integument—local irritation 
and infection may occur; tick adaptations 
suppress host response and allow feeding for 
up to 1 week.
• Salivary secretions—neurotoxins; other 
pharmacologically active compounds cause 
impaired hemostasis and immune suppression 
at the tick-feeding site.
• Pathogens—acquired when ticks feed on 
infected reservoir hosts (often rodents and 
small feral mammals); transmitted while 
feeding on dogs and cats.
Tick Biology
• Hard ticks—four life stages: egg, larva, 
nymph, and adult; larvae and nymphs feed to 
repletion before detaching and molting; after 
detachment, females lay thousands of eggs 
and die; various tick stages may survive over 
winter, tolerate long starvation, low humidity, 
as well as water deprivation. Completion of 
life cycle requires three hosts; some species 
pass all stages on the same mammal.
• T ransovarial transmission—organisms 
disseminate to the ticks’ ovaries; infected eggs 
hatch and produce infected larvae.
• T rans-stadial transmission—immature ticks 
become infected while feeding on reservoir hosts 
and maintain infection through the molt from 
one life stage to the next, transmitting organisms 
to the new host when next stage feeds.
• Ticks generally acquire hosts by a passive 
ambush process; when a suitable host brushes 
against vegetation harboring questing ticks, 
they transfer to the host.
• Amblyomma americanum  can be an active 
hunter and traverse distances of up to 18 m 
to attack a suitable host.
• Symbiotic relationship— Ixodes scapularis  
infected with Anaplasma phagocytophylum  
express an antifreeze glycoprotein gene that 
enhances survival of the tick in cold weather.
• Nervous.GEOGRAPHIC DISTRIBUTION
• Strong geographic specificities exist for 
some tick species and their associated 
pathogens, producing geographic prevalence 
of associated diseases.
• Ranges of ticks are expanding, therefore 
the geographic incidence of tick parasitism and 
infections vectored by them are expanding.
• Emergence of new tick-borne infections 
and coinfection (due to coinfected vector 
ticks or parasitism of hosts by ticks of more 
than one species).
• I. scapularis  and I. pacificus —midwest, 
northeast, southeast, and south-central 
United States and west coast, respectively.
• R. sanguineus —throughout the continental 
United States; R. sanguineus  is unique among 
hard ticks; it can survive and establish its life 
cycle inside dwellings and kennels at (low) 
household humidity (common name “kennel 
tick”).
• D. variabilis —eastern seaboard and west 
coast of United States.
• A. americanum —found throughout the 
midwest, south-central, southeast, and parts 
of the northeast United States with strong 
range expansion.
• Amblyomma maculatum —gulf coast states 
of United States with range expansion.
Species
• Cats are efficient at removing ticks; tick 
attachment and tick-vectored diseases 
including Lyme disease, anaplasmosis, and 
cytauxzoonosis have been diagnosed in 
domestic felines.
SIGNS
• Attached ticks or tick-feeding cavities may 
be seen on the skin.
• Irritation secondary to bite.
• Petechia secondary to infectious organisms 
(Rickettsia , Anaplasma platys ).
• Blood-loss anemia (direct effect); thrombo -
cytopenia, anemia, inclusion bodies in 
neutrophils, monocytes, red blood cells 
secondary to transmitted infectious 
• Limb/joint abnormalities secondary to 
infectious organisms ( Borrelia burgdorferi  and 
other organisms implicated in oligo- and 
• Cardiac—Lyme carditis ( B. burgdorferi ), 
manifests typically as atrioventricular block; 
rare and poorly documented in dogs.
• Renal—unique, generally fatal protein-
losing nephropathy in dogs infected with 
B. burgdorferi  linked to immune complexes 
associated with antigen and antibody from 
• Rocky Mountain Spotted Fever—vague or 
non-specific symptoms of fever, lethargy, joint 
pain, gastrointestinal symptoms, focal 
hemorrhages (Rickettsia rickettsii).• Paralysis—neurotoxins secreted from tick 
salivary glands produce ascending weakness 
and paralysis.
• Pyogranulomatous myositis, periosteal 
reaction, neutrophilia, antigenic stimulation, 
and amyloid deposition in viscera in 
Hepatozoon americanum  infection in which 
the dog serves as the intermediate and 
reservoir host following tick ingestion.
• Weight loss, anemia, lethargy, fever, 
neutrophilia, hyperglobulinemia and hypo -
albuminemia in Hepatozoon canis  infection. 
Infection occurs by digesting the tick ( A. 
americanum ), which is the definitive host.
CAUSES
Ticks—attracted to hosts by warmth, presence 
of carbon dioxide, physical contact, and 
host-associated odors.
• Domestic animals—can be in close contact 
with ticks due to invasion of ticks into 
suburban environments and expansion of 
suburban environment into surrounding 
forests, prairies, and coastline areas.
• T ravel—increases risk for exposure.
• Risk is expanding as new cycles for 
maintenance of infectious organisms are 
emerging (and being discovered).
  DIAGNOSIS
N/A
• Vector-borne disease (VBD) panels provide 
clinicians the ability to test blood for multiple 
agents by using serology and/or PCR.
• IDEXX Snap 4DxPlus Test—in-office rapid 
screening test for multiple VBD; detects 
antibodies (C6 ELISA) against B. burgdorferi , 
E. canis, E. ewingii, A . phagocytophilum , A. 
platys , and Dirofilaria immitis  antigens in 
canine serum, plasma, or whole blood.
• ABAXIS VetScan FLEX4 Rapid T—detects 
antibodies against A. phagocytophilum , 
A. platys , B. burgdorferi , E. canis , E. chaffeensis , 
E. ewingii , and Dirofilaria immitis  antigens in 
canine whole blood, serum or plasma.
• Tests are sensitive and specific; 
B. burgdorferi  test does not crossreact with 
vaccine-induced antibodies.
  TREATMENT
• Outpatient after removal of ticks.
• Removal—as soon as possible to limit time 
available for pathogen or neurotoxin 
transmission; grasp ticks close to the skin with 
fine-pointed tweezers and gently pull free.

Canine and Feline, Seventh Edition  1339
TNURSING CARE
Wash feeding cavity with soap and water; 
generally sufficient to prevent local 
Application of hot matches, petrolatum jelly, 
or other materials not only fails to cause tick 
detachment but allows for longer periods of 
attachment and feeding.
See Prevention/Avoidance.
  FOLLOW-UP
• Perimeter control and avoiding environ -
ments that harbor ticks.
• Frequent tick checks and tick removal.
• Year-round tick prevention.
• Tick control does not always equal control 
of tick-borne diseases: Products should 
quickly kill or prevent attachment and 
feeding by the tick.
• Tick-borne pathogens—may be transmitted 
very rapidly (viruses) or require several 
hours ( R. rickettsii ), less than 1 day 
(A. phagocytophilum ), 1–2 days ( B. burgdorferi ), 
or 2–3 days ( Ehrlichia  species and B. canis).
• Ingestion of infected ticks makes tick 
control problematic for prevention of 
infection with Hepatozoon  species.
Insecticides and Acaricides
• Acaricides meant only for dogs must not be 
applied to cats.
• Acaricidal collars—amitraz, deltamethrine, 
and flumethrin (Preventic, Seresto, and 
Scalibor, respectively).
• Spot-on treatments—fipronil, permethrin, 
flumethrin, etofenprox.
• Oral treatments—isoxazolines: fluralaner, 
afoxolaner, lotilaner, and sarolaner. Fluralaner 
is also available as a spot-on for dogs and cats. 
Sarolaner combined with selamectin is 
available as a spot-on for cats.• Disease transmission interruption studies 
have been published for products containing 
fipronil, amitraz, isoxazolines, permethrin, 
and synthetic pyrethroids; rapid killing and 
clinical repellence are essential to prevent or 
interrupt tick feeding.
Tick-borne diseases or tick paralysis.
• Canine babesiosis— B. canis.
• Rocky Mountain spotted fever— R. rickettsia .
• Canine monocytic ehrlichiosis— E. canis or 
E. chaffeensis .
• Cyclic thrombocytopenia— A. platys .
• Granulocytic anaplasmosis— 
A. phagocytophilum  and E. ewingii .
• Lyme disease— B. burgdorferi .
• American canine hepatozoonosis—caused 
by protozoa H. americanum , following 
ingestion of an infected tick.
• Canine hepatozoonosis— caused by 
H. canis following ingestion of an infected tick.
• Tick paralysis—caused by a neurotoxin; 
affects acetylcholine synthesis and/or 
liberation at the neuromuscular junction of 
the host animal; ascending flaccid paralysis 
initially affects the pelvic limbs 5–9 days after 
tick attachment.
VACCINES
Currently for Lyme disease there are three 
types for dogs: (1) whole-cell, killed bacterin: 
LymeVax, Duramune Lyme, and Nobivac 
Lyme, (2) outer surface protein A (OspA): 
Recombitek Lyme, and (3) chimeric 
recombinant (OspA and 7 types of OspC): 
Vanguard crLyme. Efficacy studies which 
duplicate natural exposure are lacking.
• Ticks may parasitize wildlife, domestic 
animals, or humans at different stages in their 
developmental cycles; infections acquired in 
early life stages may be transmitted when 
ticks feed again in the next stage.
• Humans, if parasitized, may be exposed to 
organisms in infected ticks. B. burgdorferi , A. phagocytophilum , R. rickettsia , and 
E. chaffeensis  are also human pathogens.
SYNONYMS
Acariasis
SEE ALSO
• Lyme Borreliosis.
• Rocky Mountain Spotted Fever.
• IFA = immunofluorescent antibody assay.
• VBD = vector-borne disease.
https://www.cdc.gov/ncezid/dvbd/index.html
Burgio F , Meyer L, Armstrong R. A 
comparative laboratory trial evaluating the 
immediate efficacy of fluralaner, afoxolaner, 
sarolaner and imidacloprid + permethrin 
against adult Rhipicephalus sanguineus  (sensu 
lato) ticks attached to dogs. Parasit Vectors 
2016, 9:626.
Miller Jr. WH, Giriffin CE, Campbell KL. 
Parasitic skin diseases. In: Muller and Kirk’s 
Small Animal Dermatology, 7th ed. 
Philadelphia, PA: W.B. Saunders, 2013, 
pp. 294–296.
Schorderet-Weber S, Noack S, Selzer PM, 
et al. Blocking transmission of vector-borne 
diseases. Int J Parasitol Drugs Drug Resist 
2017, 7:90–109.
Resnick
acknowledge the prior contribution of Steven 
A. Levy.
available online(continued)  Ticks and Tick Control

1340  Blackwell’s Five-Minute Veterinary Consult  
TToad Venom Toxicosis
  BASICS
OVERVIEW
• T wo species of primary concern in North 
America—Colorado River toad ( Incilius 
alvarius ) and marine/cane toad ( Rhinella 
marina ); marine toad more toxic; both can be 
fatal. • I. alvarius  found in Arizona, New 
Mexico, Texas, and Colorado; R. marina  
found in Florida, Texas, and Hawaii. Both 
species have body lengths up to 23 cm; easily 
distinguishes them from other toad species. 
Active during periods of high humidity 
(monsoon season—late summer Arizona, 
New Mexico, Texas, and Colorado for 
Colorado River toads); most encounters occur 
during evening, night, or early morning. 
• Toxin—produced in parotid glands; 
defensive; rapidly absorbed across the victim’s 
mucous membranes; contains several major 
components: indole alkyl amines (similar to 
the street drug LSD), cardiac glycosides, and 
noncardiac sterols. On average 590 mg of 
crude secretions released from a single R. 
marina —100 mg of crude bufotoxin lethal to 
10–15 kg dog. Sublingual/buccal absorption—  
bypasses gastrointestinal tract; first pass 
metabolism allows systemic exposure to 
unmetabolized bufogens. Rapidly absorbed 
across gastrointestinal mucosa and quickly 
eliminated. Crosses blood–brain barrier 
readily (rapid CNS effects).
Primarily dogs; rarely cats.
SIGNS
• Rapid onset. • A cane toad sitting in a 
water dish for several hours can leave enough 
residual toxins to kill dogs. • Salivation 
primary sign— excessive  within seconds of 
exposure. • Toxicity varies with species, size 
and geographical location. If not in one of the 
regions cited above, unlikely  to contain highly 
toxic secretions.
• Crying/pawing at the mouth. • Frothing at 
mouth. • Ataxia—stiff gaited. • Seizures. 
• Animal found dead with toad in mouth.
• Profuse hypersalivation. 
• Hyperexcitability/vocalization. • Brick red 
buccal mucous membranes. • Hyperthermia. 
• Collapse. • Marked cardiac ventricular 
arrhythmia—less common with Colorado 
River toad. • Cyanosis. • Dyspnea. • Mydriasis. 
• Nystagmus. • Pulmonary edema. 
• Neurological signs. • Shock.CAUSES & RISK FACTORS
• Living in indigenous geographic region for 
species and in close proximity to toads. 
• Moist, warm, outside environment. 
• Outdoor animal.
  DIAGNOSIS
• Caustics or other oral irritants. • Hyperthermia. 
• Heat stroke. • Hypocalcemia. • Hypoglycemia. 
• Serotonin syndrome. • Organophosphate or 
carbamate pesticides.
• May note hypercalcemia or hyperkalemia. 
• Elevated serum glucose. • Elevated urea 
nitrogen.
Magnesium level—ventricular cardiotoxicity 
cases.
Electrocardiogram—ventricular arrhythmias.
  TREATMENT
• Marine toad intoxication—medical emergency; 
death common. • Decontamination—flush 
mouth for 5–10 minutes with copious quantities 
of water. • Hyperthermia (>40.6°C/105°F)—
provide a cool bath; remove from bath once 
temperature reaches 39.4°C (103°F). • Maintain 
airway. • Rapid evaluation of cardiac function. 
• Supportive therapy—correct electrolytes; acid–
base imbalances. • Ingested toad—may require 
endoscopic removal or surgery. • Seizure 
potential— high with the truly toxic toads; emesis 
only performed by DVM who understands this 
concept.
• Atropine 0.04 mg/kg (1/4 of dose IV, 
remainder IM or SC)—reduces salivation; helps 
prevent aspiration; use with bradycardia, heart 
block, or other sinoatrial node alterations as a 
result of the digitalis-like effect of the toxin; not 
recommended if severe tachycardia present. 
• Esmolol or propranolol—esmolol is very 
short acting and may be used as a test dose. If 
arrhythmia responds to treatment, propranolol 
is used because the duration of action is much 
longer (hours; see Contraindications/Possible 
Interactions); rapid administration may be 
required to combat tachyarrhythmias; may be 
repeated in 20 minutes or require continuous IV infusion for persistent arrhythmias: 
◦ Esmolol 0.05–0.1 mg/kg IV q5min—
maximum dosage of 0.5 mg/kg. ◦ Propranolol 
0.02 mg/kg IV slowly as needed—maximum 
dosage of 1 mg/kg. • Digoxin-specific Fab 
fragments (Digoxin Immune Fab) have been 
used successfully to treat toad venom induced 
cardiotoxic effects. • Anticonvulsant therapy—
diazepam 0.5–1.0 mg/kg IV. • Lipid emulsion 
(20%)— anecdotally, IV intralipids may reduce 
bufadienolide (very lipophilic) toxicity.
• Cardiac disease or bronchial asthma—
patient may not tolerate the use of beta-
blockers such as esmolol and propranolol. Use 
a test dose of esmolol (very short duration of 
action) and monitor closely before using 
propranolol (much longer duration of 
action). • Anesthetics (e.g., pentobarbital)—
may depress function of an already compromised 
myocardium; use with caution.
  FOLLOW-UP
• Continuous electrocardiographic monitoring—  
recommend until patient is fully recovered. 
• Colorado River toad intoxication—patients 
usually normal within 30 minutes of onset of 
treatment; death uncommon if treated; do not 
underestimate the risk of secondary heatstroke. 
• Marine toad intoxication—medical 
emergency; death common.
Brubacher JR, Lachmanen D, Ravikumar PR, 
et al. Efficacy of digoxin specific Fab fragments 
(Digibind) in the treatment of toad venom 
poisoning. Toxicon 1999, 37:931–942.
Gowda RM, Cohen RA, Khan IA. Toad 
venom poisoning: resemblance to digoxin 
toxicity and therapeutic implications. Heart 
2003, 89:e14.
Johnnides S, Eubig P , Green T. Toad 
intoxication in the dog by Rhinella marina : 
the clinical syndrome and current treatment 
recommendations. J Am Anim Hosp Assoc 
2016, 52:1–8.
Reeves MP . A retrospective report of 90 dogs 
with suspected cane toad ( Bufo marinus ) 
toxicity. Aust Vet J 2004, 82:608–611.
Author  Daniel E. Keyler
Michael E. Peterson.

Canine and Feline, Seventh Edition  1341
TTooth—Missing
  BASICS
OVERVIEW
• Absence of tooth or teeth due to develop-
mental conditions, not to trauma or 
extraction:
 ◦Total anodontia—absence of all teeth due 
to failure in development.
 ◦Partial anodontia—failure in develop-
ment of part of the dentition (hypodontia, 
oligodontia—some teeth missing).
 ◦Edentulous—“without teeth” but 
primarily due to tooth loss (e.g., end-stage 
periodontal disease).
• In dogs, premolars or distal molars are the 
most common missing teeth.
• If a deciduous tooth is missing, its 
permanent successor will probably not 
develop as well.
• If a permanent tooth is missing, and the 
deciduous tooth is still present (persistent), if 
root structure is stable, that deciduous tooth 
might stay functional for a long time; lack of 
permanent tooth should be documented.
• Any breed, size or gender, but smaller 
breeds predominate.
• Some familial tendencies, breed prevalence.
SIGNS
• Tooth not present (crown and root).
• Alveolar bone and gingival margin at site is 
regular, smooth, even slightly “scalloped” 
• No tooth structure present radiographically.
• Dog/cat.
• Total and partial anodontia—typically 
hereditary and may be associated with 
ectodermal dysplasia (Chinese crested dogs).
• Bilateral patterns of missing teeth may be 
indicative of a genetic or familial tendency, as 
opposed to a single missing tooth.
  DIAGNOSIS
• Delayed eruption.
• Unerupted teeth (see Dentigerous Cyst).
• Invulsed tooth.
• Extracted or lost due to periodontal disease 
or trauma.
• Fusion tooth—if two teeth have fused, 
there will be reduction in the tooth number 
(see Tooth Formation/Structure, Abnormal).CBC/BIOCHEMISTRY/URINALYSIS
IMAGING
• Intraoral radiographs essential.
• Determine if teeth are truly missing, and/or 
if permanent teeth are present, if deciduous 
teeth are persistent/retained.
• Pre-purchase full-mouth radiographs on 
8- to 10-week-old puppies can identify if 
permanent tooth structures are present 
(though there is no guarantee they will 
erupt).
• Appropriate preoperative diagnostics when 
  TREATMENT
• None indicated unless an unerupted or 
involved tooth is found radiographically.
DRUGS OF CHOICE
  FOLLOW-UP
None needed.
  MISCELLANOUS
• If multiple teeth are missing or they are 
missing bilaterally, there could be a familial 
tendency; consider removing from breeding 
stock.
• In some breeds (Doberman pinscher, 
Rottweiler) or Schutzhund trained dogs, any 
missing teeth may be considered a serious 
fault, and pre-purchase radiographs on 
puppies may be helpful.
SEE ALSO
• Dentigerous Cyst.
• Tooth Formation/Structure, Abnormal. Suggested Reading

1342  Blackwell’s Five-Minute Veterinary Consult  
TTooth Formation/Structure, Abnormal
  BASICS
OVERVIEW
Variation in Tooth Size
• Macrodontia—crown oversized, root 
normal.
• Microdontia—crown normal shape, but 
small.
• Peg tooth—small, cone-shaped tooth with a 
single cusp.
Variation in Tooth Structure/Shape
• Fusion—two separate tooth buds joined to 
form an entire single tooth or joined at the 
roots by cementum and dentin.
• Gemination—developing tooth bud 
undergoes an incomplete split, resulting in 
two crowns with a common root canal.
• Dilacerated—distorted or malformed tooth 
(crown or root)—a general term that may be 
used for many different presentations.
• Dens-in-dente (tooth within a tooth)—
external layers invaginate into internal 
structures with varying severity.
• Shell teeth—crown present, but little to no 
root development.
• Amelogenesis imperfecta—hereditary 
reduction in the amount of developed enamel 
matrix.
• Stress or stimulus (trauma) at time of 
development can alter tooth formation.
• Infection, trauma to tooth buds, or 
traumatic extraction of deciduous teeth 
during permanent tooth formation can 
significantly alter the structure.
• Genetic or familial tendencies not known 
for most conditions.
Dog/cat.
SIGNS
• Fusion—fused crown will be larger than a 
single tooth. There will be a reduced number 
of teeth (two counted as one).
• Gemination tooth—actual number of teeth 
will be unaltered, but one tooth will be larger, 
with duplication of part of the crown (and 
possibly roots radiographically); “Siamese twin.”
• Dilacerated teeth:
 ◦Any variation in structure or form—extra 
root, curved root.
 ◦Each tooth must be evaluated for 
integrity of the pulp system, as any 
disruption in the continuity of the crown 
and roots may result in exposure of the 
pulp to the external environment.  DIAGNOSIS
• T rauma to tooth structures.
• Developmental abnormalities.
IMAGING
• Discontinuity between crowns and roots.
• Possible pulp exposure and pulp stones.
• Roots are convergent with wide canals 
(nonvital pulp).
• Periapical/root abscessation with extensive 
bone loss.
• Intraoral radiographs.
• With any abnormal structure (dilaceration), 
pulpal integrity and the potential for 
crowding must be evaluated.
  TREATMENT
• Abnormal development of mandibular first 
molars in small-breed dogs.
 ◦Dilaceration is more common, sometimes 
described as dens-in-dente.
 ◦As one of the first permanent teeth to 
form, there may be a mechanical challenge 
(lack of space) in small dogs that impedes 
proper crown–root development.
 ◦Invagination of the enamel and/or 
cementum at the neck of the tooth, often 
with some degree of gingival recession.
• Fusion teeth—no treatment is necessary 
unless the groove between the two teeth and/
or crowns extends to the gingival margin or 
below (nidus for periodontal disease).
• Gemination tooth—if tooth crowding 
results, extraction may be necessary.
• Dilacerated tooth—if there is pulpal 
exposure or compromise, extraction is 
generally necessary. In some cases, endodontic 
and restorative therapy may allow preserva-
tion of the tooth.
support during anesthetic procedures.  FOLLOW-UP
• Good prognosis on teeth with moderate 
changes (peg teeth, fusion teeth, gemination 
tooth).
• Guarded prognosis on dilacerated teeth 
with pulpal compromise, though extraction 
typically successful.
Small Animal Dentistry, 2nd ed. Ames, 
IA: Blackwell, 2012 (for additional topics, 
NJ: Wiley-Blackwell. 2019.
Regezi JA, Sciubba JJ, Jordan RCK. Oral 
Pathology Clinical Pathologic Correlations, 
4th ed. St. Louis, MO: Saunders, 1999, 
pp. 367–370.

Canine and Feline, Seventh Edition  1343
TTooth Root Abscess (Apical Abscess)
  BASICS
OVERVIEW
• An abscess is a localized collection of pus in a 
cavity formed by the disintegration of tissues.
• An abscess spreads along the pathway of 
least resistance from the tooth apex, resulting 
in osteomyelitis:
 ◦If this infection perforates through the 
cortex of the bone in which the tooth is 
encased, it can result in a cellulitis that can 
burst through the skin to create a cutaneous 
draining tract.
 ◦The drainage can also occur through the 
alveolar mucosa, above the mucogingival 
line (parulis).
• Can involve any teeth; the maxillary fourth 
premolars are most commonly affected, followed 
by the canines and mandibular first molars.
• Periodontal disease can extend down the 
root of the tooth to the apex, infecting the 
pulp and resulting in endodontic involvement 
(perio-endo lesion).
• Systemic spread of bacteria (bacteremia and 
pyemia) and the persistence of inflammation 
can affect other organ systems.
• A tooth root abscess can have an acute or 
chronic phase:
 ◦Phoenix abscess—acute exacerbation of a 
chronic periapical abscess.
• Can arise without the presence of bacteria 
(sterile abscess).
• Dogs (primarily) and cats.
• Any age:deciduous or permanent teeth can 
be involved.
• Usually occurs in active animals that bite or 
chew a lot.
SIGNS
• Tooth is visibly broken with or having near 
pulpal exposure—90% of cases.
• Tooth may appear discolored.
• Tooth is not sensitive to percussion or cold 
or hot liquids or foods—note: acute tooth 
fracture with pulp exposure would be sensitive.
• Facial swelling—usually localized but can 
spread, resulting in a cellulitis.
• Cutaneous sinus (draining tract) exuding 
pus—suppurative apical periodontitis:
 ◦Suborbital abscess due to maxillary 
fourth premolar involvement is a common 
• On oral examination, especially of the 
maxilla, there may be a red, raised lesion 
(parulis) at the anticipated location of the 
tooth apex. Often present where the attached 
gingiva meets the alveolar mucosa (mucogingival 
line) or above.
• Facial sensitivity may be slight but could be 
extensive if there is no draining.
• Tooth may be clinically asymptomatic, yet 
inflammation and bacteremia may be present.• Tooth may be asymptomatic for a long time 
but will be affected eventually—subclinically 
or even years later.
• In the absence of a fractured tooth with an 
exposed canal, a deep periodontal pocket may 
extend to the apex of one or more roots, 
resulting in a similar abscess.
• May present as a jaw fracture, especially if 
the abscess affects the lower canine teeth or 
lower first molar. Slight trauma can cause a 
pathologic fracture of the mandible.
• Tooth may be loose and painful on palpation.
• May have facial lymphadenitis.
• Animal does not want to chew, especially 
on the affected side (plaque and calculus may 
accumulate), or will bite, but release quickly 
instead of holding on.
 ◦Some animals stop eating, the great 
majority do not.
• Sinusitis—maxillary sinus is most commonly 
affected.
• Sense of smell (olfactory capabilities) may 
be affected, especially with drug, bomb, or 
food-sniffing working dogs.
• Any pulpal trauma—direct blow with 
fracture of crown; chewing hard objects 
(carnassial teeth); defense (fighting—canine 
teeth); malocclusive trauma; tug-of-war; bone 
plating that damaged roots.
• Advanced periodontal disease—a deep 
periodontal pocket can involve the apex 
where bacteria can enter the pulp system, 
especially at the palatal root of a small dog.
• Bacteria—the pulp can be affected by 
bacteria from dental caries, exposed dentinal 
tubules, or extension into endodontic system.
• Thermal heat resulting in pulpal necrosis—
electrical cord burns, iatrogenic caused by use 
of electrocautery for gingival surgery, 
overpolishing during an oral hygiene 
procedure or use of rotary burs.
  DIAGNOSIS
• Normal radiographic anatomy—chevron 
effect and mental formina.
• Tooth resorption—radiographs show no 
apical lucency or abscessation, but rather a 
disintegration of the root and/or crown with 
the loss of the periodontal ligament.
• Oral tumor.
• Squamous cell carcinoma and fibrosarcoma 
(rapidly growing and invasive) and 
ameloblastoma (slowly enlarges). These tumors 
can displace teeth, which often become mobile.
• Cementomas—radiographically show 
enlarged apical roots with a thin radiolucent 
zone continuous with the periodontal ligament.
• Cysts—radiographs usually show a very 
large lytic area involving any part of the root 
and/or unerupted crown: ◦Radicular cysts, apical periodontal 
 ◦Dentigerous cyst—occurs from the 
follicular cyst of an impacted or embedded 
tooth (usually the first mandibular 
premolars in dogs); in which case the 
radiograph show a tooth within the cyst.
• Periapical scar—usually occurs on an 
endodontically treated tooth where there has 
been no further increase in the radiographic 
apical lucency after a 6-month post-treatment 
period.
• Normal anatomy—mental foramens can be 
mistaken for apical lucencies on radiographic 
interpretation (the middle mental foramen 
just apical to second mandibular premolar).
CBC may show a leukocytosis and/or a mild 
regenerative anemia.
IMAGING
• Intraoral radiographs are the most 
commonly utilized diagnostic aid; 
demonstrates thickening of the apical 
periodontal ligament space; ill-defined 
radiolucency; shows bone loss at the apex as 
the lesion becomes chronic.
• As the lesion progresses, radiographic 
lesions consistent with osteomyelitis and 
cellulitis occur.
• Must be differentiated from chevron 
effect:this is evident radiographically in the 
small teeth that commonly develop a tooth 
root abscess.
• If fistulization has occurred, can place a 
gutta percha cone into the sinus tract and take 
a radiograph to identify the affected tooth.
• T ransillumination with a strong fiber-optic 
light can help the clinician by distinguishing 
between a vital and necrotic pulp (compare to 
similar tooth on contralateral side).
• Apical area has a central area of liquefaction 
necrosis containing disintegrating neutrophils 
and cellular debris, surrounded by macrophages, 
lymphocytes, and plasma cells; can see 
bacteria.
• Extension of the lesion into cancellous bone 
results in inflammation of the periapical bone 
and resorption.
• Chronic changes may develop tracts that 
can be lined with epithelium; osteomyelitis or 
cellulitis lesions may become fibrotic with a 
capsule (radicular cyst and/or a periapical 
periodontal granuloma).
  TREATMENT
• Must surgically drain and remove the focus 
• Extraction of the tooth involved, with 
curettage of the apical infected area.

1344  Blackwell’s Five-Minute Veterinary Consult  
T• Chronic conditions require surgical removal 
of the granulation tissue and curettage of the 
tract.
• Endodontic treatment of the involved 
tooth (surgical root canal if apical legion 
large).
• Medical management can be instituted 
temporarily until surgery can be performed.
• After treatment, cold packs on the area will 
help reduce inflammation.
• Following extraction, oral rest is 
recommended: soft diet, no hard chew toys, 
until the gingiva is healed.
• Broad-spectrum antibiotics recommended 
preoperatively to help prevent systemic spread 
of infection and improve tissue quality.• Broad-spectrum antibiotic postoperatively 
for 7–10 days.
• Due to its ability to penetrate bone, 
clindamycin is recommended at a minimum 
of 5.5–11 mg/kg twice daily for dogs and 
once daily for cats.
• Second choice is amoxicillin/clavulanic acid 
12.5–25 mg/kg orally twice daily.
• Analgesics preoperatively, intraoperatively, 
and postoperatively for 3–4 days.
• If a surgical endodontic treatment or an 
extraction was performed, a protective collar 
may be required.
  FOLLOW-UP
• For extractions—recheck the site 10–14 
days postoperatively. Soft diet and remove 
chew toys until healed gingiva is confirmed at 
recheck appointment.• Recheck in 6–12 months with intraoral 
• Avoid traumatic injuries (e.g., letting 
the dog chase cars, hard chew toys, stop 
fighting).
• Curtail bite work—avoid handler sleeves 
that have tears or hole in them and avoid 
torsion movements.
• Check the mouth regularly for any trauma 
to additional teeth.
N/A
Authors  Heidi B. Lobprise and Jessica 
Johnson
Consulting Editor  Heidi B. LobpriseTooth Root Abscess (Apical Abscess)  (continued)

Canine and Feline, Seventh Edition  1345
TTorsion of the Spermatic Cord
  BASICS
OVERVIEW
• Testicular torsion (also known as torsion of 
the spermatic cord) results from twisting of 
the spermatic cord which leads to occlusion 
of venous outflow from the testis.
• Prolonged occlusion leads to ischemia, 
infarction, and necrosis.
• Abdominally retained testes are at greater 
risk of torsion, thought to be because of 
increased range of motion as compared to 
testes confined to the scrotum.
• Neoplastic testes, with increased weight, 
also have a greater likelihood of undergoing 
torsion.
• Torsion of descended (scrotal) testes has 
also been described.
• Systems affected—reproductive.
• Intact male animals.
• Higher incidence in cryptorchid males.
• Very rare (but reported) in cats.
• Mean age 6–8 years (dogs).
• Cases of testicular torsion in both young 
(<10 months) and old (>10 years) dogs have 
SIGNS
• Hyporexia/anorexia.
• Hind limb lameness.
• Pyrexia.
• Dysuria.
• Scrotal edema.
• Inguinal swelling.
• Bilateral symmetric alopecia (secondary to 
Sertoli cell tumor).
• Feminization (secondary to Sertoli cell 
tumor).
• Testicular neoplasia (most commonly 
Sertoli cell tumors and seminomas).
• High physical exertion.
• Exuberant libido and expression of sexual 
  DIAGNOSIS
• Gastrointestinal disorder.
• Renal disease.• Peritonitis.
• Splenic torsion.
• The results of laboratory testing and 
imaging will aid in ruling in or out the above.
Nonspecific results in cases of testicular 
torsion, but useful in differentiating between 
other possible conditions.
IMAGING
• Secondary to torsion, the affected testis 
typically appears hypoechoic in comparison 
to the contralateral (unaffected) testis.
• The diameter of the spermatic cord may be 
enlarged.
• The affected testis may be spherical in 
shape, as opposed to ovoid.
• Color Doppler ultrasound is very useful to 
visualize blood flow (or lack thereof).
Nonspecific for diagnosing testicular torsion 
but valuable in assessing differential 
diagnoses.
  TREATMENT
• Surgical removal of affected testis on an 
emergent basis
• Inpatient care for immediate postoperative 
monitoring
• In theory, if torsion of a scrotal testis is 
rapidly identified and detorsion occurs 
quickly, this testicle could be salvaged. No 
such cases are reported in the literature. In a 
canine experimental model of testicular 
torsion, ultrasonographic changes occurred in 
all subjects by one hour after torsion, which 
were seen before irreversible histological 
lesions were induced.
None specifically indicated other than routine 
postoperative pain control and antimicrobial 
coverage as indicated by the particular case.
  FOLLOW-UP
Removal of undescended testes prior to 
development of neoplasia and/or torsion.EXPECTED COURSE AND PROGNOSIS
Good prognosis for recovery following 
surgery in cases of uncomplicated testicular 
torsion.
• Cryptorchidism (generally accepted to be a 
heritable, sex-limited autosomal recessive 
trait).
• Testicular neoplasia (Sertoli cell tumor and 
seminoma most commonly, with an increased 
rate of occurrence in retained testes).
If a retained testis is removed and a descended 
testis preserved, the ethical considerations of 
using the animal for breeding and potential 
for hereditary cryptorchidism should be 
impressed upon owner. Bilateral orchiectomy 
is the most commonly recommended course 
of treatment in literature reports.
Hecht S, King R, Tidwell AS, Gorman SC. 
Ultrasound diagnosis: intra-abdominal 
torsion of a non-neoplastic testicle in a 
cryptorchid dog. Vet Radiol Ultrasound 
2004, 45:58–61.
Author  Karen A. Von Dollen

1346  Blackwell’s Five-Minute Veterinary Consult  
TToxoplasmosis
  BASICS
Toxoplasma gondii —obligate intracellular 
coccidian protozoan parasite that infects 
nearly all mammals. Felids are the definitive 
hosts and all other warm-blooded animals 
serve as intermediate hosts.
• Three main modes of transmission: 
(1) congenital, (2) ingestion of bradyzoites 
encysted in tissue of intermediate hosts, or 
(3) ingestion of sporulated oocysts within 
feces of felids.
• Most cats infected via ingestion of 
intermediate hosts; release bradyzoites in 
gastrointestinal tract that invade enteroepithe-
lium; ultimately undergo sexual reproduction 
and oocyte formation; oocysts require 1–5 
days to sporulate and become infectious after 
being passed in feces.
• Acute disseminated infection—organisms 
spread via blood or lymph; tachyzoites rapidly 
divide within extraintestinal tissues; causes 
focal necrosis, granulomatous inflammation; 
• Following acute infection, slowly dividing 
bradyzoites encyst in host tissue, usually not 
clinically apparent unless immunosuppression 
or concomitant illness allows organism to 
reactivate to tachyzoite stage.
• Infection acquired during pregnancy—pos-
sible placentitis and transplacental transmis-
sion of tachyzoites to fetus; can induce 
abortion or clinical disease (kittens).
• Multisystemic.
• Ophthalmic—~ 80% of affected cats have 
uveitis.
• ~30% of cats and up to 50% of people 
serologically positive for T. gondii .
• Most animals asymptomatic.
Worldwide
Species
Cats more commonly symptomatic than dogs.
Mean age 4 years; range 2 weeks–16 years.
More common in male cats.
SIGNS
• Determined by site and extent of organ 
damage.
• Acute—at time of initial infection, rapid 
clinical course.• Chronic—reactivation of encysted infection 
due to immunosuppression, slower clinical 
course.
• Lethargy, depression, anorexia.
• Fever.
• Ocular discharge, photophobia, miotic 
pupils (cats).
• Neurologic—ataxia, seizures, tremors, 
paresis/paralysis, or cranial nerve deficits.
• Digestive tract—vomiting, diarrhea, 
abdominal pain, and/or jaundice.
• Stillborn kittens.
Cats
• T ransplacentally infected kittens may be 
stillborn or die before weaning; surviving 
kittens—anorexia, lethargy, high fever.
• Signs reflect necrosis/inflammation of lungs 
(dyspnea, increased respiratory noises), liver 
(icterus, abdominal enlargement from 
ascites), and CNS (encephalopathy).
• Postnatal exposure.
• Respiratory and gastrointestinal 
abnormalities most common—anorexia, 
lethargy, high fever, dyspnea, weight loss, 
icterus, vomiting, diarrhea.
• Ocular abnormalities common—uveitis 
(aqueous flare, hyphema, mydriasis), iritis, 
detached retina, iridocyclitis, and/or keratic 
precipitates.
• 10% of patients show neurologic 
abnormalities—blindness, stupor, incoordin -
ation, circling, torticollis, anisocoria, or 
seizures.
Dogs
• Puppies—generalized infection; fever, 
weight loss, anorexia, tonsillitis, dyspnea, 
diarrhea, vomiting.
• Adults—localized infections associated with 
neural and muscular systems.
• Neurologic manifestations variable; result 
of diffuse neurologic inflammation—seizures, 
tremors, ataxia, paresis, paralysis, muscle 
weakness.
• Ocular inflammation—rare.
• Cardiac involvement—usually subclinical.
CAUSES
T. gondii
• Ingestion of intermediate hosts, environment 
contaminated with cat feces.
• Immunosuppression—may predispose to 
infection or reactivation: feline leukemia 
virus (FeLV), feline immunodeficiency virus 
(FIV), feline infectious peritonitis (FIP), 
hemotropic mycoplasma, canine distemper, 
glucocorticoids, chemotherapy, postrenal 
transplant.  DIAGNOSIS
Cats
• Anterior uveitis—FIP , FeLV, FIV, other 
infectious, immune-mediated, trauma; 
lens-induced, corneal ulceration, lymphoma.
• Dyspnea—asthma, cardiogenic, 
pneumonia, neoplasia, heartworm disease, 
pleural space disease, diaphragmatic hernia, 
trauma.
• Meningoencephalitis—viral, fungal, 
parasitic, bacterial, idiopathic (feline 
polioencephalomyelitis).
Dogs
• Neurologic abnormalities—infectious, 
inflammatory, toxic, metabolic.
CBC (Cats)
• Normocytic normochromic anemia.
• Leukopenia—50% of patients with severe 
disease; primarily lymphopenia.
• Neutropenia with degenerative left shift.
• Alanine aminotransferase and aspartate 
aminotransferase—increased enzyme 
• Hyperbilirubinemia (25% of cats).
Urinalysis (Cats)
• Mild proteinuria.
• Bilirubinuria.
Serology
• IgM—serologic titer of choice for 
diagnosis of active infection; elevated 2 
weeks post infection (usually with onset of 
clinical signs) and persists for up to 3 
months:
 ◦Prolonged titer—reactivation or delay in 
antibody class shift to IgG (due to immuno-  
• IgG—titers rise 2–4 weeks post infection, 
persist >1 year; single high titer not diagnostic 
for active infection; 4-fold increase over a 
3-week period suggests active infection.
• Serum antigen—positive 1–4 weeks post 
infection; remains positive during active or 
chronic infections (not helpful to determine 
infection type).
• PCR—to verify presence of T. gondii  in 
biologic specimens:
 ◦Prudent choice in suspect cases since 
many protozoa are morphologically similar 
and difficult to distinguish histopathologically.

Canine and Feline, Seventh Edition  1347
TIMAGING
Radiographs—mixed pattern of patchy 
alveolar and interstitial pulmonary infiltrates; 
pleural and abdominal effusions and hepato  - 
megaly may be present.
• Bronchoalveolar lavage, pulmonary 
fine-needle aspirate (cats with respiratory 
disease)—organism can be identified 
cytologically.
• Effusion cytology—organism rarely 
detected during acute infection.
• Cerebrospinal fluid (patients with 
encephalopathy)—high leukocyte count 
(both mononuclear cells and neutrophils) and 
protein.
• Fecal—active fecal oocyte shedding occurs 
for 1–3 weeks after infection in the cat and 
usually not during clinical disease; not 
recommended for determining whether or 
not an individual cat is infected with T. gondii . 
Oocysts may be detected on routine 
examination in asymptomatic cats but are 
morphologically indistinguishable from 
Hammondia  spp. and Besnoitia .
• Potentially no gross lesions.
• Necrotic foci—up to 1 cm; most often in 
liver, pancreas, mesenteric lymph nodes, 
lungs; necrosis of brain (1 cm areas of 
discoloration).
• Ulcers and granulomas—in stomach and 
  TREATMENT
• Inpatient—severe disease; patient cannot 
maintain adequate nutrition or hydration.
• Confine—patients with neurologic signs.
Dehydration—IV fluids.
• Cats—prognosis guarded in patients 
needing therapy; response to therapy is 
inconsistent.
• Poorer prognosis for neonates and 
immunocompromised animals.
• Clindamycin 12.5–25 mg/kg PO, IV, IM 
q12h; continue at least 2 weeks after clinical 
• 1% prednisone drops—q8h for uveitis.PRECAUTIONS
Clindamycin—anorexia, vomiting, and 
diarrhea (dose-dependent).
• Sulfadiazine 30 mg/kg PO q12h in 
combination with pyrimethamine 0.5 mg/kg 
PO q12h for 2 weeks; can cause depression, 
anemia, leukopenia, and thrombocytopenia, 
especially in cats.
• Folinic acid 5 mg PO q24h or brewer’s 
yeast 100 mg/kg PO q24h—correct bone 
marrow suppression caused by above therapy.
  FOLLOW-UP
• Examine 2 days after treatment initiation 
for resolution of clinical signs; uveitis should 
resolve within 1 week.
• Neuromuscular deficits take longer to 
resolve, should see partial resolution within 
2 weeks (some deficits may be permanent).
• Examine 2 weeks after resolution of clinical 
signs to determine if treatment may be 
Cats
• Diet—prevent ingestion of raw meat, 
bones, viscera, or unpasteurized milk 
(especially goat’s milk), or mechanical vectors 
(flies, cockroaches). Only well-cooked meat 
should be fed.
• Behavior—prevent free-roaming to hunt 
prey (birds, rodents) or to enter buildings 
where food-producing animals are housed.
• Prognosis—guarded; varied response to 
drug treatment.
• Acute—prompt and aggressive therapy 
often successful.
• Residual deficits (especially neurologic) 
cannot be predicted until course of therapy is 
completed.
• Ocular disease—usually responds to 
• Severe muscular or neurologic disease—
usually chronic debility.
• Young dogs—distemper.
• Cats—renal transplant recipients, FeLV, 
FIP , FIV; FIV infection does not affect 
clinical outcome or the ability of the animal 
to mount a protective immune response to 
subsequent reinfection.AGE-RELATED FACTORS
Disease worse in neonates.
• Of most concern is infection of pregnant 
women or immunocompromised individuals. 
Pregnant women should avoid contact with 
cats excreting oocysts in feces, contact with 
soil and cat litter, and should not handle or 
eat raw meat (to kill organism, cook to 
>66°C/150°F):
 ◦Young cats are most likely to be shedding 
oocysts.
 ◦Important : oocysts need to be sporulated 
to be infectious. Unsporulated oocysts are 
shed in the feces and require at least 24 
hours to sporulate; daily cleaning of litter 
box should reduce risk of exposure to 
infectious form.
• Cats—healthy animals with a positive 
antibody titer pose little danger to humans; 
animal with no antibody titer at greater risk 
of becoming infected, shedding oocysts in 
the feces, and constituting a risk to humans.
• Avoid contact with oocysts or tissue 
cysts—do not feed raw meat; wash hands and 
surfaces (cutting boards) after preparing raw 
meat; boil drinking water if source is unreliable; 
keep sandboxes covered to prevent cats from 
defecating in them; wear gloves when 
gardening; wash hands and vegetables before 
eating; empty cat litter boxes daily; disinfect 
litter boxes with boiling water; control stray 
cat population.
• T. gondii  causes abortion in sheep; prevent 
cats from ingesting placenta or aborted fetuses 
and keep cats from defecating in sheep feed to 
break the life cycle.
• Parasitemia during pregnancy—spread of 
organism to fetus; probably does not happen 
unless first-time infection of dam occurs 
during pregnancy (as with humans).
• Placental transmission rare.
Diseases of the Dog and Cat, 3rd ed. 
St. Louis, MO: Saunders Elsevier, 2006, 
pp. 754–775.
available online(continued)  Toxoplasmosis

1348  Blackwell’s Five-Minute Veterinary Consult  
TTracheal Collapse
  BASICS
• Static or dynamic reduction in the luminal 
diameter of the large conducting airway with 
respiration. • Can involve the cervical trachea, 
the intrathoracic trachea, or both segments. 
• Airway collapse (bronchomalacia) refers to 
collapse of lobar bronchi and smaller airways, 
which can be seen in conjunction with 
tracheal collapse (tracheobronchomalacia) or 
alone. • Compression of the trachea or 
bronchi due to hilar lymphadenopathy or 
external mass lesions—not considered part of 
this condition.
• Hypocellular tracheal cartilage in the cervical 
region identified historically in some small-
breed dogs. • Lack of chondroitin sulfate and/
or decreased glycoproteins within the cartilage 
matrix results in a reduction in bound water 
and loss of rigidity in the cartilage. • Causes of 
bronchomalacia not established—cartilage 
abnormalities could include a mechanism 
similar to cervical tracheal collapse, defects in 
chondrogenesis, nutritional deficiencies, or 
degenerative changes caused by chronic airway 
disease. • Collapse—weak tracheal cartilage 
allows flattening of the normal ring structure; 
trachea collapses in a dorsoventral direction 
when pressure fluctuates within the airway 
lumen. During inspiration, intrapleural 
pressure becomes more negative leading to a 
drop in intra-airway pressure. Atmospheric 
pressure exceeds airway pressure in the cervical 
region and lack of cartilage support results in 
cervical collapse. During forced expiration, 
intrapleural pressure becomes positive and 
exceeds intrathoracic intra-airway pressure. 
When cartilaginous airway walls are weakened 
by bronchomalacia, intrathoracic airway 
collapse occurs, on expiration. • Increased 
tension on the trachealis dorsalis muscle or 
neurogenic atrophy of the muscle causes 
stretching of the dorsal tracheal membrane 
with protrusion into the airway lumen. 
• Coughing—mechanical trauma to the 
tracheal mucosa from collapse of the dorsal 
tracheal membrane exacerbates airway edema 
and inflammation. • Upper airway obstruction 
worsens clinical signs, and chronic increases in 
respiratory effort could lead to secondary 
abnormalities in laryngeal structure and 
function. • Small airway disease augments the 
trans-airway pressure gradient and potentiates 
collapse in the intrathoracic region.
• Respiratory—chronic airway irritation. 
• Cardiovascular—pulmonary hypertension. 
• Nervous—can be involved when syncope 
develops from hypoxia or a vasovagal reflex 
associated with cough.GENETICS
Under investigation. T racheal collapse common 
in small toy breed dogs. Bronchomalacia seen 
in large and small breeds.
Common clinical entity.
Worldwide
Species
Primarily dog, rarely cat.
T racheal collapse—miniature poodles, Yorkshire 
terriers, Chihuahuas, Pomeranians, other small 
and toy breeds. Bronchomalacia—all breeds.
• Middle-aged to elderly—onset of signs at 
2–14 years of age. • Severely affected animals 
<1 year of age.
SIGNS
• Usually worsened by excitement, heat, 
humidity, exercise, or obesity. • Dry honking 
cough. • Often have a chronic history of 
intermittent coughing or difficulty breathing. 
• Retching—often seen due to attempts to 
clear respiratory secretions from the larynx. 
• Tachypnea, exercise intolerance, and/or 
respiratory distress—common. • Cyanosis or 
syncope—seen in severely affected individuals.
• Increased tracheal sensitivity—virtually always 
seen. • Respiratory distress—inspiratory with 
cervical collapse; expiratory with intrathoracic 
collapse. • Stridor or musical sounds ausculted 
over narrowed cervical trachea. • An end-
expiratory snap—heard when a large intra -
thoracic airway collapses during forceful 
expiration then reopens. • Crackles—due to 
small airway collapse (inspiratory or expiratory) 
or chronic bronchitis. • Expiratory wheezes 
suggest concurrent bronchitis. • Mitral 
insufficiency murmurs—often found 
concurrently in small-breed dogs. • Normal to 
low heart rate and/or marked respiratory 
arrhythmia. • Loud second heart sound—
suggests pulmonary hypertension. 
• Hepatomegaly—cause unknown.
CAUSES
• Unknown etiology—congenital, nutritional, 
or familial defects of chondro  genesis suspected. 
• Chronic airway inflammation suggested to 
contribute to bronchomalacia but relationship 
not clearly established. Seen with chronic 
bronchitis or eosinophilic 
bronchopneumopathy.
• Obesity. • Airway infection or 
inflammation. • Upper airway obstruction. 
• Endotracheal intubation.  DIAGNOSIS
• Infectious tracheobronchitis.
• T racheal or laryngeal obstruction or foreign 
body. • Chronic bronchitis. • Pneumonia—
viral, bacterial, fungal, parasitic, eosinophilic. 
• Bronchiectasis.
• CBC—can show an inflammatory 
leukogram secondary to chronic stress or 
concurrent infection. • Increased liver 
enzymes common.
Elevated bile acids—mechanism unclear.
IMAGING
• Airway collapse evident on a lateral thoracic 
radiographic in a large percentage of dogs 
with airway collapse, however, the location of 
collapse on static radiographs agreed with the 
site determined by fluoroscopy in <50% of 
cases. • Inspiratory radiographs—show 
primarily cervical collapse and collapse at the 
thoracic inlet. • Expiratory radiographs—
show intrathoracic tracheal collapse; can also 
note collapse at the carina, ballooning of the 
cervical trachea, and cranial herniation of the 
lung lobe through the thoracic inlet. 
• Right-sided heart enlargement—can be 
seen secondary to chronic pulmonary disease 
and cor pulmonale, or heart can be 
artifactually enlarged due to obesity or breed 
conformation.
Dynamic collapse of the cervical or intra -
thoracic trachea and/or dorsal tracheal 
membrane can be visible during tidal 
respirations—usually more easily identified 
after induction of cough. Cranial lung 
herniation through the thoracic inlet is 
common.
Caution is warranted in anesthetizing and 
intubating dogs with tracheal collapse because 
endotracheal tube irritation can worsen 
clinical signs. Loss of respiratory drive from 
anesthetic drugs or excess excitement on 
recovery can precipitate airway obstruction.
Tracheal Wash
Use oral intubation (rather than the transtra -
cheal approach) with a small endo  tracheal 
tube and a sterile catheter when obtaining 
samples for cytologic examination and 
bacterial culture/susceptibility.
• Grade the severity of collapse: Grade I—
slight protrusion of the dorsal tracheal 
membrane into the airway lumen; diameter 
reduced by <25%, Grade II—reduction of

Canine and Feline, Seventh Edition  1349
Tthe tracheal lumen by 50%, Grade III—
reduction of the tracheal lumen by 75%, 
Grade IV—tracheal rings flattened; <10% of 
the tracheal lumen can be seen; in some cases 
(particularly Yorkies), a double lumen trachea 
is observed, where tracheal rings have bowed 
dorsally to contact the trachealis muscle. 
• Identify small airway disease—collapse or 
inflammation. Submit airway samples for 
susceptibility; specific culture for Mycoplasma  
Cytology
• Unremarkable in uncomplicated tracheal or 
bronchial collapse. • Neutrophilia without 
intracellular bacteria or marked bacterial 
growth—indicates airway inflammation. 
• Lymphocytic inflammation is also common. 
• Sepsis and suppuration along with marked 
bacterial growth of a pathogen—suggests 
pulmonary infection.
• Dorsal trachealis muscle—elongated. 
• Cartilage rings—flattened. • T racheal 
mucosal inflammation in some cases. 
• Hypocellularity of the cartilage with low 
glycoproteins and chondroitin sulfate—can 
be noted via histopathologic examination or 
electron microscopy. • Can also see changes 
associated with chronic inflammatory airway 
disease.
  TREATMENT
• Outpatient—stable patients. • Inpatient—
oxygen therapy and sedation for severe 
respiratory distress. Sedation and cough 
suppression—butorphanol 0.1–0.4 mg/kg SC 
or IV; addition of acepromazine 0.01–
0.04 mg/kg SC or IV can enhance sedative 
effects and further reduce the cough reflex.
Monitor respiratory effort.
ACTIVITY
• Severely limited until patient is stable. 
• During management of disease—gentle 
exercise recommended to encourage weight 
loss.
DIET
• Many affected dogs improve after losing 
weight. • Institute weight-loss program with 
restriction of caloric intake; use a gradual 
weight-loss program (1–2% weight loss per 
week).
• Warn client that weight gain, 
overexcitement, and humid conditions can 
precipitate a crisis. • Advise client to use a 
harness instead of a collar. • Advise owners that tracheal collapse is irreversible and that 
treatment strategies are designed to lessen 
triggers of cough. • For surgical candidates, 
advise owner of the likelihood of complica -
tions after surgery (e.g., persistent cough, 
respiratory distress, or laryngeal paralysis); 
some patients can require a permanent 
tracheostomy. For stent candidates, advise 
owners of need for extensive follow-up to 
avoid stent fracture, migration, or granulation 
tissue formation.
• T reatment of upper airway obstructive 
disorders (elongated soft palate, everted 
laryngeal saccules)—can reduce signs due to 
tracheal collapse. • The presence of mainstem 
bronchial collapse worsens prognosis. 
• Placement of extraluminal C-shaped rings 
by a skilled surgeon in selected patients with 
cervical collapse will enhance quality of life 
and reduce clinical signs when adequate 
stabilization of the airway can be achieved 
and when bronchomalacia does not limit 
resolution of clinical signs. Postoperative 
laryngeal paralysis is a potential complication. 
• Intraluminal stents are life-saving in 
selected cases with intrathoracic airway 
collapse that fail aggressive medical 
management. Aspiration pneumonia is 
common after placement.
• Narcotic cough suppressants (butorphanol 
0.5–1 mg/kg PO q4–8h or hydrocodone 
0.22 mg/kg PO q4–8h) used to break the 
cycle of cough; reduce dose rate to the least 
frequent administration that controls signs. 
Use after infection or inflammation has been 
managed. • Reduction of tracheal 
inflammation—prednisone 0.5 mg/kg PO 
q12h then 0.25 mg/kg q12h for a total of 
5–7 days may help. Inhaled steroids given 
via facemask and spacing chamber are 
preferred to avoid systemic effects of panting 
and weight gain. • Sustained-release 
theophylline 10 mg/kg PO q12h—thought 
to reduce the pressure gradient in small 
airways and decrease cough in dogs with 
intrathoracic airway collapse or 
bronchomalacia—bronchodilators have no 
effect on tracheal diameter. • Bacterial 
infection uncommon but doxycycline 
3–5 mg/kg PO q12h is sometimes beneficial, 
perhaps through reduction in bacteria within 
the airway or reduction of inflammation.
Avoid long-term steroid use because of the 
propensity for weight gain and diseases 
associated with immunosuppression.POSSIBLE INTERACTIONS
Theophylline metabolism—increased by 
concurrent treatment with ketoconazole or 
phenobarbital, which results in inadequate 
plasma concentration; decreased by fluoro -
quinolones (e.g., enrofloxacin), erythromycin, 
cimetidine, steroids, beta-blockers, mexiletine, 
and thiabendazole, which results in toxic plasma 
concentration and gastrointestinal upset, 
nervousness, or tachycardia; adjust dosages when 
concurrent use is necessary.
Over-the-counter cough suppressants—rarely 
reduce cough.
  FOLLOW-UP
• Body weight. • Exercise tolerance. • Pattern 
of respiration. • Incidence of cough.
• Avoid obesity in breeds commonly afflicted. 
• Avoid heat and humidity. • Use harness 
rather than leash.
Intractable respiratory distress leading to 
respiratory failure or euthanasia.
• Combinations of medications along with 
weight control can reduce clinical signs, but 
dogs will likely cough throughout life and can 
suffer recurrent exacerbations of disease. 
• Surgery—benefits dogs severely affected 
with cervical collapse. • Stent placement—
benefits some dogs, primarily those with 
respiratory difficulty rather than cough and 
those with intrathoracic collapse. Medications 
usually required post procedure. 
• Prognosis—based on bronchoscopic 
evidence of airway obstruction and 
development of complications.
• Chronic bronchitis. • Laryngeal paralysis. 
• Pulmonary hypertension. • Breeds of dogs 
that develop tracheal collapse also commonly 
have mitral insufficiency.
SEE ALSO
• Bronchitis, Chronic. • Canine Infectious 
Respiratory Disease.
available online(continued)  Tracheal Collapse

1350  Blackwell’s Five-Minute Veterinary Consult  
TTransitional Cell Carcinoma
  BASICS
Malignancy arising from the transitional 
epithelium within the kidney, ureters, urinary 
bladder, urethra, prostate, or vagina.
The underlying etiology of transitional cell 
carcinoma (TCC) remains unclear. It is 
possible that an environmental carcinogen 
may initiate or promote the malignant 
transformation of the transitional epithelium.
• Renal/urologic—the most common site 
affected is the trigone of the urinary bladder. 
Local invasion of the distal ureter is not 
uncommon and may lead to postrenal 
azotemia. The apex of the urinary bladder is 
more often affected in cats, although because of 
late detection the entire bladder is often 
involved by the time of diagnosis. 
• Reproductive—the vagina is a possible site of 
primary TCC. The prostate may be involved 
through local invasion, or as the primary site of 
TCC. • Other systems may be affected through 
metastases (e.g., most commonly regional 
lymph nodes and lungs; other sites include 
bone, brain, eye) or paraneoplastic syndromes 
(hypertrophic osteopathy has been reported 
secondary to TCC of the urinary bladder).
GENETICS
N/A
• <1% of all reported malignancies in dogs. 
N/A
Middle-aged to old, spayed female, small-
breed dogs most commonly reported with the 
disease.
Species
• Scottish terriers are at 18 times the risk 
compared to other breeds. • West Highland 
white terriers, Shetland sheepdogs, beagles, 
American Eskimo dogs, dachshunds. • May 
occur in any breed. • No breed predisposition 
in cats.
Dogs—8 years, range 1 to 15+ years.
Female
SIGNS
• Signs are similar to those of bacterial 
urinary tract infection or urolithiasis. • Consider TCC in animals showing 
temporary or no response to appropriate 
• Complaints of recurrent stranguria, 
pollakiuria, hematuria, dysuria, urinary 
incontinence, or any combination of the 
above signs should initiate a search for TCC. 
• Signs may temporarily respond to antibiotic 
therapy.
• Often normal. • Occasionally, urethral 
thickening can be appreciated on digital rectal 
examination or a mass might be palpable in 
the caudal abdomen/urinary bladder region. 
• Urethral/vaginal/prostatic TCC may be 
palpable on rectal examination. • Enlarged 
intrapelvic or sublumbar lymph nodes can be 
palpable on rectal examination.
CAUSES
• Dogs—reported risk factors include obesity, 
environmental carcinogens, chronic exposure 
to organophosphates or carbamates, and 
(rarely) long-term or a large bolus dose of 
cyclophosphamide. • Cats—unknown.
Dogs—Scottish terrier breed, obesity, 
exposure to organophosphates or carbamates, 
cyclophosphamide therapy.
  DIAGNOSIS
• Non-neoplastic—bacterial urinary tract 
infection, urolithasis, urethritis, vaginitis, 
prostatitis.  • Neoplastic—other primary 
neoplasia (e.g., squamous cell carcinoma, 
transmissible venereal tumor), or metastatic 
neoplasia (e.g., locally infiltrative prostatic 
• CBC and biochemistry usually within 
normal limits. • Biochemistry profile may 
show signs of renal and/or postrenal azotemia 
if ureteral or urethral obstruction exists. 
• Urinalysis may reveal epithelial cells with 
criteria of malignancy—caution should be 
exercised if the sample is inflammatory as 
epithelial cells may exhibit criteria of 
malignancy in the presence of inflammation.
• A DNA-based strategy for the detection of 
canine TCC is commercially available 
(CADET®). The assay is run on a urine 
sample and detects a mutation in the BRAF  
gene that is highly specific for TCC. • Urine 
culture and sensitivity are indicated, as 
concurrent urinary tract infection is common; 
however, caution is advised when performing 
cystocentesis on patients suspected to have TCC as tumor seeding along the needle tract 
may occur. • Biopsy (surgical, traumatic 
catheter, or cystoscopic) is gold standard for 
definitive diagnosis. Even with a low yield of 
tissue samples of some traumatic 
catheterizations, typically enough cells are 
obtained to get a cytologic diagnosis.
IMAGING
Metastatic patterns include multiple, 
well-defined interstitial nodules, increased 
interstitial pattern, and alveolar infiltrates.
• Unlikely to reveal specific urinary bladder 
disease unless the mass is mineralized (rare). 
• May reveal sublumbar lymphadenomegaly 
or bony metastasis.
Double Contrast Cystography
• Dogs—space-occupying lesion, usually at 
trigone of the urinary bladder. • Cats— 
space-occupying lesion, may be at the apex of 
the urinary bladder. • Depending on the 
primary site, IV pyelography, voiding 
urethrogram, or vaginogram may be indicated.
• 2D ultrasonography is a highly sensitive 
imaging modality, helpful in identifying 
location and extent of disease; however, not a 
reliable method for monitoring response to 
therapy. • 3D ultrasonography is a more 
accurate tool for monitoring tumor volume 
and response to therapy.
CT
CT imaging of TCC is the most accurate way 
to measure tumor volume.
• Used to obtain biopsies of the primary 
tumor and regional lymph nodes. • Surgical 
cure very unlikely due to the infiltrative 
nature of the tumor. • Because tumor seeding 
is recognized with TCC, change surgical 
gloves and instruments after handling the 
tumor.
Cystoscopy
A less invasive way to identify and biopsy 
TCC within the urinary bladder or urethra.
Traumatic Catheterization
Use a polypropylene catheter to traumatically 
obtain small tissue samples for histologic or 
cytologic diagnosis.
Ultrasound-Guided Biopsy
Not recommended, as seeding of the biopsy 
tract with viable tumor cells is a highly 
possible sequela.
• Irregular to diffuse thickening of the 
urinary bladder mucosa. • Metastasis to 
regional lymph nodes, lungs, and bones 
(i.e., vertebra, pelvis) possible.

Canine and Feline, Seventh Edition  1351
T  TREATMENT
Radiotherapy with treatment units that allow 
for intensity modulation may provide 
long-term tumor control.
Inpatient vs. Outpatient
• Initial workup and diagnosis takes 1–2 days. 
• Stable patients need not be hospitalized.
ACTIVITY
Normal
DIET
Normal, unless concurrently in renal failure.
• Long-term prognosis poor. • Palliation 
often attainable. • T rigonal location of the 
disease within the bladder makes complete 
surgical resection in dogs difficult.
• TCC is highly exfoliative and highly 
transplantable—multiple reports of surgically 
induced seeding of TCC exist. • All surgical 
instruments and gloves should be replaced after 
contacting the tumor. • Partial cystectomy 
(ideally full-thickness resection of gross disease) 
combined with piroxicam therapy may result 
in improved outcomes compared to dogs 
treated with medical therapy only. • T ube 
cystostomy placement or urethral stenting may 
prolong survival times by bypassing or 
relieving urethral obstruction.
• Piroxicam 0.3 mg/kg PO q24h with 
food—reported to have activity in 21% of 
cases with a median survival of 244 days. 
• Deracoxib 3 mg/kg PO q24h with food—
reported to have activity in 17% of cases with 
a median survival of 323 days. • A variety of 
chemotherapy drugs used at traditional 
maximally tolerated doses have activity 
against TCC, including mitoxantrone 5 mg/m2 
IV q21d, vinblastine 3 mg/m2 IV q14d, 
cisplatin 50 mg/m2 IV q21d, carboplatin 
300 mg/m2 IV q21d, and gemcitabine 
800 mg/m2 IV q7d. • Metronomic 
(continuous, low-dose) chemotherapy with 
chlorambucil 4 mg/m2 PO q24h may play a 
role in the management of this disease.CONTRAINDICATIONS
• Piroxicam—do not use in animals with 
known gastrointestinal erosions or ulcers; do 
not use in animals with renal insufficiency. 
• Piroxicam—do not combine with cisplatin. 
• Piroxicam therapy appears to be tolerated 
in cats, but at a reduced dosing frequency 
(q48h) in comparison to dogs.
• Animals with TCC may have renal damage 
either due to hydroureter, hydronephrosis, or 
pyelonephritis secondary to chronic urinary 
tract infection associated with the tumor. 
• Dogs being treated with chemotherapy 
should be monitored for myelosuppression. 
• Seek advice before initiating therapy if 
Cisplatin should not be used concurrent with 
other nephrotoxic drugs (e.g., aminoglycoside 
antibiotics).
Antibiotics—antibiotic therapy should be 
administered as necessary.
  FOLLOW-UP
• Contrast cystography or ultrasonography 
every 6–8 weeks to determine disease status. 
ultrasound every 2–3 months to monitor for 
Advise client regarding frequent urination 
following cyclophosphamide therapy to 
minimize contact time with the urinary 
• Urethral or ureteral obstruction and renal 
failure. • Metastatic disease to regional lymph 
nodes, lungs, or bone. • Recurrent urinary 
tract infection. • Urinary incontinence. 
• Myelosuppression of gastrointestinal 
toxicity secondary to chemotherapy. 
• Gastrointestinal ulceration secondary to 
piroxicam therapy.
• Progressive disease likely. • Median 
survival—no therapy: 4–6 months; with 
therapy: 6–12+ months.  MISCELLANEOUS
• Recurrent urinary tract infections. 
• Postrenal azotemia. • Paraneoplastic 
None
None
N/A
SYNONYMS
None
Fulkerson CM, Knapp DW. Management of 
transitional cell carcinoma of the urinary 
bladder in dogs: a review. Vet J 2015, 
205:217–225.
Marvel SJ, Seguin B, Dailey DD, et al. 
Clinical outcome of partial cystectomy for 
transitional cell carcinoma of the canine 
bladder. Vet Comp Oncol 2017, 
15:1417–1427.
Mochizuki H, Shapiro SS, Breen M. 
Detection of BRAF mutation in urine DNA 
as a molecular diagnostic for canine 
urothelial and prostatic carcinoma. PLOS 
One 2015, 10:e0144170.
Radhakrishnan A. Urethral stenting for 
obstructive uropathy utilizing digital 
radiography for guidance: feasibility and 
clinical outcome in 26 dogs. J Vet Intern 
Med 2017, 31:427–433.
Schrempp DR, Childress MO, Stewart JC, 
et al. Metronomic administration of 
chlorambucil for treatment of dogs with 
urinary bladder transitional cell carcinoma. 
242:1534–1538.
available online(continued)  Transitional Cell Carcinoma

1352  Blackwell’s Five-Minute Veterinary Consult  
TTransmissible Venereal Tumor
  BASICS
OVERVIEW
• Sexually, or other direct contact, transmitted, 
naturally occurring tumor.
• Appears to be more common in temperate 
areas and large cities.
Predisposition in intact dogs of either sex, 
however, routes of nonsexually contact 
transmission permits disease manifestation in 
neutered and spayed dogs.
SIGNS
• Red, friable, lobulated mass on the mucosa 
of the vagina, penis or other nonreproductive 
organ mucous membranes.
• Oral and nasal mucosa may be affected.
• Owners may report blood dripping from 
the affected area or excessive licking of the 
genital area.
• Proliferative or exophytic tumor protrusion 
may be noticed.
• Direct transplantation of tumor cells onto 
abraded mucosa, either by coitus, oral, or 
nasal transmission.
• Intact, free-roaming dogs are at greater than 
average risk.
  DIAGNOSIS
• Other neoplasia (e.g., squamous cell 
carcinoma, cutaneous lymphoma).
• Vaginal hyperplasia or pseudo-estrus.
• Urinalysis (free-catch) reveals hematuria 
and abnormal round cell populations in 
some patients if the tumor is within the 
N/A
IMAGING
• Thoracic radiographs, although this tumor 
type is rarely metastatic.
mesenteric lymph nodes.
• Careful palpation of regional lymph nodes, 
and perform aspirates with cytology when 
• Examination of impression smears or 
aspirates of the tumor reveals homogenous 
sheets of round to oval cells with prominent nucleoli, scant cytoplasm, and multiple clear 
cytoplasmic vacuoles.
• Biopsy offers definitive diagnosis.
  TREATMENT
• May spontaneously regress with appropriate 
immunologic response, treatment is 
recommended as spontaneous remissions 
are not reliable.
• Surgical excision of tumors is often 
followed by recurrence.
• Radiotherapy alone may be curative.
• Medical therapy is often curative.
• Vincristine sulfate 0.5–0.7 mg/m2 IV once 
weekly for 2 weeks beyond complete 
resolution of gross disease.
• If only partial or no remission, doxorubicin 
30 mg/m2 IV every 3 weeks may have activity.
• Myelosuppression secondary to vincristine 
or doxorubicin administration.
• Doxorubicin may be cardiotoxic, use with 
caution once a cumulative dose of 150 mg/m2 
is reached.
• Tissue sloughing if either vincristine or 
doxorubicin is administered perivascularly.
  FOLLOW-UP
CBC and platelet count before each 
chemotherapy treatment.
• Neuter animals.
• Prevent animals from roaming free in 
endemic areas.
• T umor recurrence possible following 
incomplete surgical excision or reexposure.
• Metastatic disease uncommon, but reported 
to occur in regional lymph nodes, eye, and 
Most cases of transmissible venereal tumor 
have an excellent response to therapy 
(primarily chemotherapy or radiotherapy) 
and an excellent prognosis.  MISCELLANEOUS
None
• Pregnant animals should not be treated 
with chemotherapy.
• Animals may be infected with transmissible 
venereal tumor during coitus.
Ganguly B, Das U, Das AK. Canine 
transmissible venereal tumour: a review. Vet 
Comp Oncol 2016, 14(1):1–12.

Canine and Feline, Seventh Edition  1353
TTraumatic Dentoalveolar Injuries (TDI)
  BASICS
• T raumatic dentoalveolar injuries (TDI) 
may be broadly categorized into two major 
groups: (1) dental fractures and (2) luxation 
injuries.
• Dental fractures include enamel infraction, 
enamel fracture, enamel–dentin (uncomplicated) 
fracture, enamel–dentin–pulp (complicated) 
fracture, crown–root fracture (with or 
without pulpal involvement) and root 
fracture.
• Luxation injuries include concussion, 
subluxation, luxation (lateral, intrusive and 
extrusive) and avulsion and are often associated 
with a fracture of the alveolar process.
• An avulsion is an injury in which the tooth 
has been completely displaced out of its 
socket.
• Untreated pulpal exposure invariably leads 
to pulpitis, pulpal necrosis and periapical 
• Pulpitis and pulpal necrosis may also occur 
with enamel–dentin fractures, if the fracture 
line is close to the pulp chamber, which 
exposes a large number of dentinal tubules 
that may allow microbial contamination.
• Concussion injuries may also lead to 
pulpitis and pulpal necrosis.
Endodontic infection may cause systemic 
• 26.2% of dogs and cats had at least 1 TDI 
with a mean of 1.45 TDI per patient.
• The prevalence of TDI in dogs and cats 
with concurrent maxillofacial fractures 
increases to near 70%.
Species
Juveniles tend to have more TDI associated 
with maxillofacial fractures, though TDI 
prevalence tends to increase throughout 
adolescence and peaks between 3 and 6 years 
of age.
SIGNS
Crown Fractures
• Clinical loss of tooth crown substance; 
enamel only, or enamel and dentin.
• Enamel–dentin fractures with the fracture 
line close to the pulp chamber—pale pink 
pulp is visible through the dentin.
• In enamel–dentin–pulp fractures, the pulp 
chamber is exposed.
• Acute enamel–dentin–pulp fractures may 
be associated with hemorrhage from the pulp.Crown–Root Fractures
• Fracture line may be visible as it extends 
into the gingival sulcus.
• The “slab” fracture of the maxillary fourth 
premolar tooth extends subgingivally into the 
root.
Root Fractures
• At any point along the length of the root.
• Fracture line transverse or oblique; segments 
may remain aligned or be displaced.
• Abnormal mobility of a periodontally 
sound tooth may raise suspicion of a root 
fracture.
Luxation Injuries
• Severely concussed teeth may take on a 
blue/pink/purple/gray discoloration often 
referred to as intrinsic (endogenous) staining.
• Intrusive luxation—tooth appears shorter 
than normal; no tooth mobility detected.
• Extrusive luxation—tooth appears longer 
than normal and is mobile both vertically and 
horizontally.
• Lateral luxation—tooth crown is displaced 
in either a labial or palatal/lingual direction.
• Avulsion—the tooth has been completely 
displaced out of the socket. The tooth may or 
may not remain attached to the gingiva.
• Luxations and avulsions are often 
accompanied by gingival lacerations.
CAUSES
• Altercations with other animals, motor 
vehicle accidents, falls from height, contact 
with a moving object, or simply sustained 
during playful activity, collision with another 
animal or object or even during chewing/
mastication.
• Since these injuries often occur during 
unsupervised activities, the mechanism of 
injury is often unknown.
• Free-roaming behavior increases risk of 
trauma.
• The maxillary canine tooth is the most 
commonly luxated/avulsed tooth.
• Advanced periodontitis will predispose to 
luxations and avulsions.
  DIAGNOSIS
• Crown fracture—attrition, abnormal tooth 
• Root fracture—luxation; severe periodontitis. 
Imaging needed.
• Luxation—root fracture where the coronal 
segment is displaced.
• Avulsion—tooth exfoliated due to severe 
periodontitis.
• Noncontributory.
• Unaffected by tooth fracture.IMAGING
General
• Intraoral radiography is mandatory.
• CT with appropriate protocol for the 
dentition may be beneficial for identifying 
some root fractures.
• The presence of relatively wide root canal 
space (halted dentinogenesis) and/or periapical 
lucency (periapical periodontitis) is indicative 
of pulpal necrosis.
• Radiographic indicators of disease may not 
be present in concussion and subluxation 
injuries.
• Intrusive luxation—narrowing of the 
periodontal ligament space in the apical region.
• Extrusive luxation—widening of the 
periodontal ligament, especially in the apical 
region.
• Lateral luxation—widening and narrowing 
of the periodontal ligament space and fracture 
of the alveolar process.
• Percussion, thermal pulp testing, electric 
pulp testing are subjective methods that 
rely on patient feedback and, thus, are 
unreliable.
• Pulse oximetry has shown mixed results for 
determining pulpal vitality. This method 
should currently be considered unreliable.
Untreated pulpal exposure invariably leads to 
pulpitis and eventual pulpal necrosis and 
periapical pathology.
  TREATMENT
Depends on extent and severity of trauma to 
the patient.
ACTIVITY
Restrict as indicated by nature of trauma.
DIET
In the immediate postoperative period 
(24–72 hours), moistening the patient’s dry 
food may help decrease the chance of 
traumatizing any suture lines or splints.
A series of treatments may be necessary.
Enamel–Dentin Fractures
Remove sharp and unsupported enamel/
dentin edges with a bur and seal the exposed 
dentin with a suitable restorative material.
Enamel–Dentin–Pulp Fractures
• Requires endodontic therapy or extraction.

1354  Blackwell’s Five-Minute Veterinary Consult  
T• For recent fractures in the mature tooth: 
(1) vital pulpotomy and restoration or 
(2) conventional root canal therapy and 
• In most cases, vital pulpotomy should be 
carried out within 48 hours of the injury in 
order to prevent pulpal necrosis.
• Generally, vital pulpotomy is reserved for 
younger patients.
• Teeth treated with vital pulpotomy may 
require standard root canal treatment at a 
later date.
• Standard root canal therapy is the treatment 
of choice in older patients, when the injury is 
chronic or when the pulp is already necrotic.
Crown–Root Fractures
• T reatment of crown–root fractures follows 
the same principles as for crown fracture, 
though additional periodontal health concerns 
• Can the tooth be restored in a manner that 
can maintain periodontal health?
• Fractures that do not extend more than 
4–5 mm below the gingival margin may be 
restored with dental composites or full metal 
crown in order to maintain periodontal 
health.
• Fractures that extend further along the root 
or deeply into the furcation of a multirooted 
tooth may necessitate extraction of the tooth.
• The level of the fracture along the root 
length determines the treatment.
• Midroot and apical fractures may heal if the 
tooth is immobilized with a dental splint.
• Healing may occur by means of a den-
tinocemental callus, a fibrous union, or an 
osteofibrous union.
• Fractures in the apical 1/3 of the root carry 
best prognosis for healing.
• Fractures in the coronal 1/3 of the root 
usually require tooth extraction.
Luxations
• For lateral and extrusive luxations, 
reposition the tooth in its normal position 
and ensure appropriate occlusion; immobilize 
with a semi-rigid splint for 2–3 weeks.
• If luxation is accompanied by an alveolar 
process fracture, maintain the splint for  
1–2 additional weeks.
• Since the vascular supply at the apex is 
typically compromised, root canal therapy is 
typically necessary and is performed 7 days 
after application of the splint.• Any gingival lacerations should be sutured.
• The prognosis for intrusive luxations is 
generally considered poor; as such, extraction 
is generally recommended.
Avulsions
• The most important factor determining the 
result of treatment is the vitality of the 
periodontal ligament, which is dictated 
largely by the amount of time the tooth has 
been out of the socket.
• Optimal results are achieved if the tooth is 
replanted within 30-60 minutes of avulsion.
• Advise client to place the tooth in saline or 
milk and bring the affected animal in for 
treatment as quickly as possible.
• Avoid handling the tooth root and rinse 
gently with sterile saline solution.
• It is essential not to remove the periodontal 
ligament from the root; a viable periodontal 
ligament is necessary for healing.
• Replace the tooth in the socket and ensure 
normal position and occlusion.
• To immobilize the tooth, a semi-rigid splint 
is applied and left in place for 2–3 weeks.
• Root canal therapy is required in 7 days, 
but should not be performed at the time of 
reimplantation.
• Contraindications for replanting avulsed 
teeth are deciduous teeth, severe periodonti-
tis, caries, or tooth resorption.
• A broad-spectrum bactericidal antibiotic 
drug for 5–7 days may be used (e.g., when 
longstanding infection is present) but is 
generally not indicated.
• Daily rinsing with 0.12% chlorhexidine 
gluconate solution will diminish the need for 
prolonged administration of antibiotics.
• Appropriate analgesic regime—usually 
nonsteroidal anti-inflammatory drug for  
3–5 days.
  FOLLOW-UP
• Check a vital pulpotomy with postoperative 
radiographs after 6 and 12 months, or at 
intervals determined by clinical signs, to detect pulp death and consequent periapical changes 
indicating the need for root canal treatment.
• Check the outcome of conventional root 
canal therapy radiographically 6–12 months 
postoperatively; evidence of periapical 
pathology at this time indicates the need for 
further endodontic retreatment of the tooth.
• Monitor root fractures radiographically 3–6 
months postoperatively.
• Monitor enamel–dentin fractures with 
radiography at 4–6 months after treatment to 
assess pulpal health.
Avoid situations in which teeth are likely to 
be damaged; keep animal from chewing on 
hard objects such as rocks.
to pulpitis and eventual pulpal necrosis and 
• Arrested development of immature teeth.
The most appropriate treatment will vary 
with age.
• TDI = traumatic dentoalveolar injuries.
• Dental fracture classification: https://avdc.
org/avdc-nomenclature/
• Dental trauma guide: dentaltraumaguide.org
Soukup J. T raumatic dentoalveolar injuries. 
In: Lobprise HB, Dodd JR, eds., Wiggs’ 
Veterinary Dentistry; Principles and 
Practice, 2nd ed. Hoboken, NJ: Wiley-
Soukup J, Hetzel S, Paul A. Classification and 
epidemiology of traumatic dentoalveolar 
injuries in dogs and cats: 959 injuries in 
660 patient visits (2004–2012). J Vet Dent 
2015, 32(1):6–14.
Consulting Editor  Heidi B. LobpriseTraumatic Dentoalveolar Injuries (TDI)  (continued)

Canine and Feline, Seventh Edition  1355
TTremors
  BASICS
Rhythmic, oscillatory, involuntary, abnormal, 
or normal movement of all or part of the body.
Abnormal or normal movement caused by the 
alternate or synchronous contraction of 
reciprocally innervated, antagonistic muscles.
• Nervous.
• Musculoskeletal—muscle weakness or pain.
GENETICS
The role of genetics in tremor syndromes is 
largely unknown with the exception of 
X-linked hypomyelination in male springer 
spaniels.
N/A
• In general, any dog or cat may develop 
tremors. However, certain tremor syndromes 
have specific signalment.
• Corticosteroid-responsive tremor syndrome 
(generalized tremor syndrome, white shaker 
syndrome)—small to medium-size breed 
(<15 kg), young adult dogs (<5 years), 
regardless of coat color. A similar syndrome 
has recently been observed in 2 cats.
• Idiopathic head tremors (head bobbing)—
Doberman pinschers, English bulldogs, 
French bulldogs, boxers, and Labrador 
retrievers are overrepresented.
• Orthostatic tremors—young, adult, 
• Benign pelvic limb tremors in older 
dogs—terriers predisposed.
• Hypomyelination—puppies; chow chows, 
springer spaniels, Samoyeds, Weimaraners, 
and Dalmatians.
SIGNS
• Localized or generalized.
• Localized—most often involves the head or 
the pelvic limbs.
CAUSES
Tremors Primarily Affecting the Head
• Cerebellar lesions leading to intention 
tremors—degenerative; congenital; metabolic; 
infectious; immune-mediated; neoplastic; 
traumatic; toxic causes; vascular.
unknown cause.
Tremors Primarily Affecting the Limbs
• Orthostatic tremors—unknown cause. Seen 
in the thoracic and pelvic limbs of young, adult, giant-breed dogs. T remors are present 
when standing and disappear in ambulating 
and recumbent animals.
• Compressive lesions of the spinal cord or nerve 
roots—lumbosacral stenosis; intervertebral disc 
disease; neoplasia; discospondylitis.
• Neuromuscular disease—peripheral neuro- 
pathy; neuromuscular junction abnormality; 
myopathy.
• Metabolic disorder causing weakness—
hypoglycemia, hypoadrenocorticism, 
hypocalcemia, magnesium imbalance. 
Metabolic causes of tremors may also present 
as generalized tremors.
dogs—unknown cause.
Generalized Tremors
syndrome)—believed to be immune-mediated.
• Hypomyelination: specific defect in myelin 
formation unknown.
• Intoxications—metaldehyde (snail bait); 
mycotoxins (penitrem A and roquefortine); 
organophosphates; hexachlorophene; 
bromethalin; ivermectin; moxidectin; 
pyrethrins/pyrethroids; lead; 5-fluorouracil; 
macadamia nuts; theobromine; anatoxin-a; 
marijuana; zolpidem; clozapine, dysautonomia 
(although toxin is suspected, exact toxin is 
unknown); castor beans ( Ricinus communis ); 
carbon monoxide; mirtazapine, alfaxalone, 
diphenhydramine, many others.
• Degenerative neurologic disease—storage 
disease; Lafora disease; spongiform encephalo-  
pathy.
• Presence of concurrent metabolic diseases 
that can cause tremors (hypoglycemia, 
magnesium imbalance).
• Exposure to a known tremorgenic toxin.
• Exposure to fear-producing or hypothermia-  
inducing situations.
  DIAGNOSIS
• Differentiate tremor from constant 
repetitive myoclonus, seizures, and myokymia/  
neuromyotonia.
• Constant repetitive myoclonus—rhythmic 
contractions usually involving one or more 
pelvic limb muscles and/or muscles of 
mastication. Seen most often with distemper 
virus infection.
• Seizures—may be associated with autonomic 
disturbances (e.g., urination, defecation, and 
salivation) and alterations of consciousness.• Myokymia/neuromyotonia—characteristic 
vermicular skin rippling caused by muscle 
contraction and often brought on by 
excitement or excessive stimulation.
• Assess for additional neurologic deficits 
suggesting cerebellar disease; intention 
tremors are a clinical sign of cerebellar 
disease; intention tremors worsen when the 
patient attempts to move the head in a 
goal-oriented manner; ataxia and dysmetria 
help determine the neuroanatomic 
patient usually young at onset; sporadic; 
up-and-down (yes) or side-to-side (no) 
direction; anatomic origin unknown; no 
other neurologic deficits present and 
mentation is not affected.
• Diseases of the lumbosacral spinal cord, 
cauda equina, and associated peripheral 
nerves; musculoskeletal diseases.
• Metabolic diseases (may also cause 
generalized tremors)—hypoglycemia, 
• Neuromuscular disease—peripheral 
neuropathy; neuromuscular junction 
abnormality; myopathy.
• Young dog (6–8 weeks)—congenital 
myelination abnormality; check breed 
incidences.
• Young adult dog—assess history for toxin 
exposure; consider corticosteroid-responsive 
tremor syndrome (generalized tremor syndrome, 
white shaker syndrome) in young, small-
• Usually normal with associated primary 
brain disease.
• Assess for metabolic disease; may find 
hypoglycemia, hypocalcemia, magnesium 
imbalance, pattern consistent with hypoadreno  - 
• Some myopathies are characterized by high 
creatine kinase, aspartate aminotransferase, 
and alanine aminotransferase.
If tremors are affecting the limbs and 
weakness is suspected, consider testing for 
hypoadrenocorticism (adrenocorticotropic 
hormone stimulation test) and myasthenia 
gravis (acetylcholine receptor antibody titer).
IMAGING
• Localized to the pelvic limbs—survey 
radiography, CT, and/or MRI of the vertebral 
column and spinal cord from L4 to S3.
• Generalized tremors—in hypomyelination, 
MRI may reveal lack of myelin; in corticosteroid-
responsive tremor syndrome (generalized

1356  Blackwell’s Five-Minute Veterinary Consult  
TTremors  (continued)
tremor syndrome, white shaker syndrome) 
MRI usually normal.
• Intention tremor—MRI of the brain, with 
special attention to the cerebellum.
• CSF analysis—sensitive but nonspecific; in 
corticosteroid-responsive tremor syndrome 
syndrome) mild mononuclear pleocytosis, but 
CSF may also be normal; in other encephali -
tides involving the cerebellum, results vary 
with cause of disease and duration.
• Electromyography of hind limb muscles—
may help diagnosing neuromuscular disease if 
pelvic limb tremor.
Dependent on underlying cause of tremor.
  TREATMENT
• T reat the underlying primary disease.
• Outpatient, unless surgical treatment is 
indicated (lumbosacral disease that requires 
decompression and stabilization).
• Avoid excitement and exercise—may 
worsen many tremors.
• Degenerative neurologic diseases (e.g., 
storage disease, spongiform encephalopathy)—
no treatment available.
• Hypomyelination—generally not treatable; 
some breeds improve with maturity (e.g., 
chow chows).
no effective treatment available; benign 
tremor that occurs sporadically; has few 
health consequences.
• Suspected intoxication—remove patient 
from further exposure; consult with a poison 
control center for possible antidote.
• Usually do not respond to antiepileptic 
drugs (e.g. phenobarbital or diazepam).• T remors associated with some toxicities, 
especially metaldehyde (snail bait), may be 
treated with methocarbamol (dogs: 
50–150 mg/kg IV, maximum dose 330 mg/
kg in 24h) and appropriate decontamination.
• Corticosteroids—immunosuppressive dose 
to treat corticosteroid-responsive tremor 
syndrome (generalized tremor syndrome, 
white shaker syndrome)
• Antibiotics—for discospondylitis; choose 
on the basis of culture and sensitivity of the 
lesion, blood, or urine.
• Cerebellar diseases—depends on the 
• Gabapentin 5–20 mg/kg up to q8h may be 
helpful in treatment of some tremors.
Sympathomimetic drugs—may worsen 
  FOLLOW-UP
• Monitor the primary disease.
syndrome)—monitor weekly initially to assess 
Prevent reexposure in the cases of toxicity.
excellent prognosis, no treatment needed.
• Orthostatic tremors—slowly progressive; 
disappear when patient ambulates or when 
patient is recumbent.
• Benign pelvic limb tremors in older dogs—
can be slowly progressive; disappear when 
patient ambulates or when patient is 
recumbent.
• Hypomyelination—may stabilize and even 
improve as animal ages.
syndrome)—most respond to corticosteroid therapy; some may need low-dose 
corticosteroid therapy indefinitely.
N/A
N/A
N/A
SYNONYMS
• Shaking.
• Shuddering.
SEE ALSO
• Hypomyelination.
• Head T remors (Bobbing), Idiopathic— 
Dogs.
De Lahunta A, Glass E, Kent M. 
Uncontrolled involuntary skeletal muscle 
contractions. In: Veterinary Neuroanatomy 
and Clinical Neurology, 4th ed. St. Louis, 
MO: Saunders Elsevier, 2015, pp. 
509–524.
Feline Neurology. 2nd ed. Ames, IA: 

Canine and Feline, Seventh Edition  1357
TTrichomoniasis
  BASICS
OVERVIEW
• Enteric, pear-shaped, motile (flagellated) 
protozoa similar to Giardia —inhabits large 
intestine of cats; similar organisms live in 
intestinal tract of many mammals
• Tritrichomonas foetus  (sometimes referred to 
as T. blagburni ) causes diarrhea in cats:
◦ T ransmitted via fecal–oral route, 
ingestion of trophozoites via grooming.
◦ Parasites colonize terminal ileum, cecum, 
and colon leading to large bowel diarrhea.
• Coinfection with Giardia —common.
Young, often purebred cats—usually under 1 
year (range 3 months–13 years); particularly 
high prevalence in catteries.
SIGNS
Cats
• May or may not have symptoms of infection.
• Intermittent large bowel diarrhea, malodorous, 
occasionally contains blood and mucus.
• Anus—may become edematous, 
erythematous, and painful in kittens.
• Rectal prolapse—if anal irritation becomes 
severe.
• Diarrhea—improves with antibiotic 
treatment but reoccurs following course of 
treatment; may also show waxing and waning 
course without treatment.
• Median length of time of diarrhea is about 
9 months, with resolution in most cats by 2 
years; number of cats cohabitating will impact 
duration of clinical signs.
• Persistence of infection after resolution of 
diarrhea is common.
• Tritrichomonas foetus —causes diarrhea in 
cats, infertility and abortion in cattle.
• T. foetus  —high prevalence in purebred cats 
and densely housed populations such as 
catteries, show cats, shelters; but very low in 
feral or indoor cats.
• Pathogenic factors leading to infected cats 
developing diarrhea—endogenous bacterial 
flora, adherence of parasite to host epithelium, 
and cytotoxin and enzyme elaboration.
• Pentatrichomonas  spp. (family 
T richomonads)—inhabit large intestine of 
cats, dogs, humans; nonpathogenic in dogs 
and cats, except very rarely when it may 
become an opportunistic pathogen.
  DIAGNOSIS
Cats
Dietary indiscretion, inflammatory bowel 
disease, neoplasia (especially gastrointestinal lymphoma), drugs (antibiotics), toxins (lead), 
parasites (cryptosporidiosis, Giardia , hookworms, 
roundworms), bacterial agents (salmonellosis, 
intestinal bacterial overgrowth, clostridia), 
systemic organ dysfunction (renal, hepatic, 
pancreatic, cardiac), and metabolic 
(hyperthyroidism).
Usually normal—may reflect diarrhea.
• Direct fecal smear—very low sensitivity:
◦ Method—dilute fresh feces 50:50 in 
saline, cover slip, examine at 40× objective 
with condenser lowered to increase contrast.
◦ Distinguish from Giardia  (concave ventral 
disc, spiral forward motion)— T. foetus  has 
jerky forward motion, spindle-shaped, 
undulating membranes.
• T. foetus  trophozoites not seen on fecal 
flotation, will not survive refrigeration.
• Fecal protozoal culture—use commercial 
media in 37°C incubator (e.g., InPouch® TF); 
inoculate with 0.05 g fresh feces, examine for 
motile trophozoites daily for 12 days:
◦ Giardia  and P . hominis —do not grow 
after 24 hours in InPouch system.
• PCR (feces)—more sensitive than fecal culture.
IMAGING
N/A
N/A
  TREATMENT
• Rule out coexisting disease (cryptosporidiosis, 
giardiasis, bacterial), especially if diarrhea 
persists after specific treatment.
• T reatment may decrease the severity of 
diarrhea but may also prolong time to resolution.
• No approved treatments.
• T. foetus —poor treatment responses are 
common.
◦ Ronidazole 30 mg/kg PO q24h for 
14 days; currently preferred treatment.
◦ Metronidazole 30–50 mg/kg PO q12h, 
3–14 days.
• P . hominis —metronidazole 20 mg/kg PO 
q12h for 7 days.
• Glucocorticoids may exacerbate clinical 
disease.
• High doses of metronidazole (usually 
>30 mg/kg) for extended periods may cause 
neurologic abnormalities (e.g., vestibular 
disease).• Ronidazole may cause reversible 
neurotoxicity (similar to that seen with 
metronidazole treatment); doses above 
30 mg/kg should not be used in cats, 
treatment should be discontinued if adverse 
effects occur.
• Resistance to ronidazole and metronidazole 
  FOLLOW-UP
• Most cats spontaneously resolve their 
diarrhea but may take years (range 4 
months–2 years).
• Relapses of diarrhea are common and often 
precipitated by dietary changes, stress, 
treatments of other conditions.
T. foetus  is not considered a zoonotic agent; 
possible zoonotic transmission for 
Pentatrichomonas .
https://capcvet.org/guidelines/trichomoniasis/
Stockdale HD, Dillon AR, Newton JC, et al. 
Experimental infection of cats ( Felis catus ) 
with Tritrichomonas foetus  isolated from 
cattle. Vet Parasitol 2008, 154:156–161.
Yao C, Köster LS. T ritrichomonas foetus 
infection, a cause of chronic diarrhea in the 
domestic cat. Vet Res 2015, 46(1):35.

1358  Blackwell’s Five-Minute Veterinary Consult  
TTrigeminal Neuritis, Idiopathic
  BASICS
OVERVIEW
Sudden bilateral paralysis of trigeminal 
mandibular branches resulting in inability to 
close the mouth. Lesions are characterized by 
extensive nonsuppurative trigeminal neuritis, 
demyelination, and rare axonal degeneration 
affecting all portions of the trigeminal nerve 
and ganglion without brainstem involvement.
• Primarily adult dogs.
SIGNS
• Acute onset of a dropped jaw.
• Inability to close the mouth.
• Drooling.
• Difficulty in prehending food, messy 
eating.
• Swallowing is intact when food and water 
are placed in the caudal portion of the 
mouth.
• Approximately one-third of affected dogs 
will exhibit decreased facial sensation.
• Few dogs have sympathetic involvement of 
the head (Horner’s syndrome).
• Long-term muscle atrophy depending on 
degree of axonal involvement.
Unknown; autoimmune disorder suspected.
  DIAGNOSIS
• Musculoskeletal disorders of the temporo-
mandibular joints and jaw—differentiated by 
history of trauma, pain, and physical 
examination findings.
• Rabies—always initially consider until there 
is sufficient evidence to rule it out.
• Encephalitis involving the motor nuclei of 
bilateral trigeminal nerve.
• Neoplasia—involvement of both mandibu-
lar nerves with myelomonocytic leukemia, 
lymphoma, and neurofibrosarcoma reported; 
usually does not have an acute onset.
• Masticatory muscle myositis—presentation 
excludes this condition characterized by 
trismus and difficulty/inability to open the 
mouth (“locked jaw”).
MRI—diffuse enlargement of affected nerves 
that appear isointense to hyperintense on 
T2-weighted images if edema is present; 
contrast enhancement on post-contrast 
T1-weighted images.
• No specific test.
• Skull radiography, MRI, CSF , and muscle 
biopsy—to rule out differentials.
  TREATMENT
• Recovery within 2–3 weeks of onset. Supportive 
treatment necessary during this period.
• Outpatient if owner is able to help the 
patient eat and drink.
• Patient cannot prehend or move food and 
water to the throat but can swallow if the 
bolus is placed in the caudal portion of the 
mouth and the jaw is manually held closed. 
Water and slurry food can also be placed, 
with a syringe, in the corner of mouth with 
the head slightly elevated.
• Fluids—subcutaneously if oral support 
insufficient.
• Esophagostomy or gastrostomy tubes—
rarely necessary to maintain adequate food 
intake.
Corticosteroids not indicated as there is no 
evidence that they improve recovery. 
Furthermore, side effects (polyuria and 
polydipsia) can make management difficult.
  FOLLOW-UP
• Self-limiting disorder.
• Full recovery in 2–3 weeks.
• Bilateral symmetrical masticatory muscle 
atrophy but without trismus.
SYNONYMS
• Dropped jaw.
• T rigeminal neuropathy.
• Mandibular paralysis. Suggested Reading
Mayhew PD, Bush WW, Glass EN. 
T rigeminal neuropathy in dogs: a 
retrospective study of 29 cases (1991–
2000). J Am Anim Hosp Assoc 2002, 
38:262–270.
Schultz RM, T ucker RL, Gavin PR, et al. 
Magnetic resonance imaging of acquired 
trigeminal nerve disorders in 6 dogs. Vet 
Rad Ultrasound 2007, 48(2):101–104.

Canine and Feline, Seventh Edition  1359
TTularemia
  BASICS
OVERVIEW
• Francisella tularensis —small Gram-negative 
coccobacillus, principally found in wild 
lagomorphs and rodents; facultative intra  - 
cellular parasite that survives and grows in the 
liver, resulting in granulomas and/or 
abscesses:
◦ Type A is more virulent and found in 
rabbits and ticks, type B is waterborne and 
found in rodents and ticks.
◦ In United States most cases found in 
Missouri, Alaska, Oklahoma, South Dakota, 
Tennessee, Kansas, Colorado, Illinois, Utah, 
Maine, New York, and New Jersey.
◦ Increasing number of tularemia outbreaks 
in regions of Europe outside the classic 
endemic areas in recent years.
• Absent from United Kingdom, Africa, 
South America, Australia.
• T ularemia infection in cats follows a 
bimodal seasonal incidence curve with 
peaks in spring and late summer–fall, and 
may reflect the seasonality of the disease in 
the rabbit.
• Infection—ingestion of tissue or body 
fluids of an infected mammal or contaminated 
water, bitten by blood-sucking arthropod 
(tick), flies, mites, midges, fleas, or mosquitoes; 
few bacteria needed to infect cats through 
skin, airways, or conjunctiva; larger number 
required to infect through gastro  intestinal tract:
◦ Skin contact—organism multiplies 
locally (papule) 3–5 days after contact; 
ulcerates 2–4 days later; spreads via 
lymphatics to regional lymph node (LN) 
and bloodstream; results in septicemia 
(lung, liver, spleen, LN, bone marrow).
◦ Ingestion—may involve lymphadenopathy 
of cervical and mesenteric LN followed by 
septicemic spread; distribution of lesions to 
face, oral cavity, tonsils, intestines, and LN.
• Acute disease—2–7 days after contact with 
organism.
• Has high aerosol-related infection rate, low 
infectious dose, and ability to induce fatal 
disease.
• F. tularensis  is considered a potential 
biologic warfare agent; occurrence of clusters 
of cases in companion animals may indicate 
potential human risk.
• Cat—occasionally.
• Dog—rarely.
SIGNS
• Sudden onset of anorexia, lethargy, fever 
(104–106°F/40–41°C).
• Enlarged submandibular and cervical LN.• Tender abdomen, palpable mesenteric LN, 
hepatomegaly—depending on stage of disease.
• Multifocal white patches or ulcers along 
glossopalatine arches and tongue.
• Icterus.
• Organism— Francisella tularensis ; all 
Francisella  biogroups may infect cats but 
differ in virulence.
• Hunting or outdoor cats in endemic areas .
• Infected wildlife in the area of hunting 
activity.
• Exposure to infected blood-sucking 
  DIAGNOSIS
• Pseudotuberculosis ( Yersinia 
pseudotuberculosis )—usually vomiting and 
diarrhea.
• Babesiosis ( Babesia/Theileria ) (dogs and 
cats).
• Calicivirus (cats).
• Feline immunodeficiency virus.
• Toxoplasmosis (cats).
• Initially severe panleukopenia; then 
leukocytosis with left shift, toxic neutrophils, 
• Hyperbilirubinemia, bilirubinuria.
• Alanine aminotransferase activity 
Serology with tube agglutination or ELISA—
reference laboratory; all animals do not 
necessarily respond serologically to infection 
(false negatives possible).
• Caution : use extreme care when working 
with infected specimens or isolates.
• Direct smear—lesion or biopsy; difficult to 
see organism on Gram staining.
• Culture—by reference laboratory only; 
blood, pleural fluid, LN aspirate onto 
cysteine- or cystine-containing media; not 
recoverable on routine laboratory media.
• Direct fluorescent antibody testing—
clinical materials or tissues; rapid assay of 
infection status.
• Molecular testing of tissues in laboratories 
with validated diagnostic protocols.
glossopalatine arches and tongue.• Oral, tonsillar ulceration.
• Lymphadenopathy of cervical, retropharyngeal, 
or submandibular LN with abscessation.
• Diffuse intestinal lesions.
• Mesenteric lymphadenopathy, hepatospleno  - 
megaly, icterus.
  TREATMENT
• Inpatient with good nursing care; infection 
control protocols (personal protective gear) 
very important due to low infectious dose/
zoonotic nature of disease.
• Early treatment important to prevent high 
mortality; treatment often unsuccessful.
• T reat for ectoparasites.
T reat all cases empirically until laboratory 
confirmation obtained.
• Little information available on the efficacy 
of antimicrobials; high mortality if patient not 
treated early .
• Early treatment with amoxicillin 22 mg/kg 
PO q8h for 5–7 days or 22 mg/kg IM, SC 
q12h for 5 days, in combination with 
gentamicin 4.4–6 mg/kg IV, IM, SC q24h for 
7 days has been successful.
• Enrofloxacin 10 mg/kg PO, IV q24h (dog), 
5 mg/kg PO, IV q24h (cat) may be effective.
  FOLLOW-UP
• Monitor for disseminated intravascular 
coagulation—may occur late in the infection.
• Monitor renal function during gentamicin 
therapy.
• Avoid travel to endemic areas.
• Endemic areas—confine animals to limit 
exposure to and ingestion of wildlife and 
ectoparasites (ticks); ectoparasite control by 
periodic spraying or dusting of animal and 
pastures.
• Neuter cats—limit hunting behavior, 
wildlife exposure.
• Take precautions to limit contamination of 
food and water with carcasses of infected 
wildlife.
Prognosis poor if not treated early; prognosis 
poor if mesenteric LN palpable.

1360  Blackwell’s Five-Minute Veterinary Consult  
T  MISCELLANEOUS
• Extremely high.
• Human cases related to direct dog contact 
via bite, scratch or face snuggling/licking, 
direct contact with dead animals retrieved by 
domestic dogs, contact with infected ticks; 
dogs with oral contact with diseased wildlife 
or carcasses may act as “living fomites” to 
contaminate humans.
• All personnel in contact with patient or 
body fluids must use face mask, gloves, and 
gowns to avoid infection.
• In emerging disease areas, cat ownership is a 
disease risk for humans.• Bites and scratches pose a risk for humans.
• Do not mistake for plague or bite abscess 
in cats.
SYNONYMS
• Rabbit fever.
• Deerfly fever.
• Market men’s disease.
• LN = lymph node(s).
disease.php?name=tularemia&lang=en
• http://www.phac-aspc.gc.ca/lab-bio/res/
psds-ftss/msds68e-eng.php
• http://www.cdc.gov/tularemia/
Foley JE, Nieto NC. T ularemia. Vet 
Microbiol 2010, 140:332–338.Kwit NA, Schwartz A, Kugeler KJ, et al. 
Human tularaemia associated with 
exposure to domestic dogs-United States, 
2006-2016. Zoonoses Public Health 2019, 
66:417–421.
Mani RJ, Morton RJ, Clinkenbeard KD. 
Ecology of tularemia in central US 
endemic region. Curr T rop Med Rep 2016, 
3:75–79.
Woods JP , Panciera RJ, Morton RJ, et al. 
Feline tularemia. Compend Contin Educ 
Pract Vet 1998, 20:442–457.
Consulting Editor  Amie KoenigTularemia  (continued)

Canine and Feline, Seventh Edition  1361
U
Unruly Behaviors: Jumping, Pulling, Chasing, Stealing—Dogs
  BASICS
• Jumping—standing on rear legs with front 
legs on a person or object or leaping in the air 
with or without landing against the person.
• Pulling—to exert force on the leash to cause 
motion towards the source of the force (the 
dog). • Chasing—pursuing a moving person, 
animal, or object. • Stealing—the taking of 
an item not intended to be used by the dog.
• May be within the range of normal dog 
behaviors. • Insufficient outlets for normal 
activities may contribute. • Jumping up may 
be associated with excessive greeting but can 
be associated with separation anxiety or social 
anxiety. • Pulling can be associated with 
different motivational states including but 
not limited to fear, anxiety, excitement, and 
predatory behavior. • Pathologic hyperactivity 
and anxiety disorders may rarely be a 
Species
Dogs
Herding and hunting breeds may be more 
likely to chase.
More common in younger dogs but occurs at 
any age.
SIGNS
• Jumping up on people occurs more 
commonly in association with arrivals, 
departures, or other greetings; also associated 
with exploring countertops or tables.
• Pulling may be more likely in the beginning 
of a walk or when seeing, hearing, or perhaps 
smelling a stimulus (e.g., person, other dog, 
object of interest) but can occur at any point.
• Items displaced, damaged, chewed, or 
ingested are common complaints in stealing.
• Usually unremarkable unless underlying 
medical problems. • Nails worn down.
CAUSES
• Jumping up is normal greeting and play 
behavior. Excitement, encouragement of the 
behavior, or inadvertent rewarding perpetuates 
it. Separation anxiety may result in excessive 
jumping on owners when returning home or 
leaving. Social anxiety may cause overly 
exuberant greeting of visitors, with jumping.  • Pulling can occur when a dog is not taught 
how to walk on loose leash or due to different 
motivational states. A dog may pull toward or 
away from something it is afraid of (avoid -
ance) or toward something that is fear-evoking 
(aggression) or that it is excited about 
greeting. • Stealing is a normal acquisitive 
behavior. It can be an attention-seeking 
behavior or motivated by the appeal of the 
odor, texture, or taste of an item with which 
to chew, eat, or play. Stealing can occasionally 
be comfort-seeking or related to separation 
anxiety, in which the dog may steal an item 
when anxious as the owner is preparing to 
leave or when the dog is separated from the 
owner but the owner is still in the house.  
• Chasing is a normal behavior, as part of 
herding, hunting, play, and defense.
• Inadequate exploratory or social enrichment. 
• Stealing food—restricted or weight-reduc-
tion diets, phenobarbital, benzodiazepines, 
glucocorticoids, hyperadrenocorticism, and 
diabetes mellitus. • Chasing—common in 
  DIAGNOSIS
• Separation anxiety—escapes or attempts 
escape from confined areas in the owner’s 
absence. Often occurs at entrances or when 
confined. Usually associated with other signs 
consistent with separation anxiety, including 
vocalization, urination, defecation, 
destruction, or salivation, in the owner’s 
absence.
• Other anxiety or phobia (e.g., thunderstorm, 
fireworks).
• May have abnormalities consistent with 
system affected.
As indicated to rule out source of pain or 
endocrine disease (low-dose dexamethasone 
suppression test [LDDST], urine 
cortisol:creatinine ratio [UC:Cr ratio], bile 
acids).
IMAGING
Not indicated unless suspicion of foreign 
body or to rule out medical causes.
  TREATMENT
Outpatient management.ACTIVITY
Increase the dog’s daily exercise, opportunities 
for mental stimulation including food-related 
enrichment (food-filled toys, search and find 
games). If problem related to anxiety, must 
address underlying anxiety as well.
DIET
Review energy requirements, amount fed, and 
number of meals per day in food-stealing 
cases.
Jumping
• During training, prevention of jumping 
up is essential. • A head collar and leash 
can facilitate training by preventing jumping 
up or gently guide the dog away from 
jumping.
• Greeting visitors outside might diminish 
jumping behavior. The dog’s access to the 
situation can be restricted by confinement 
(e.g., other room, crate) or on leash with 
owner until the visitor is seated, which may 
also reduce the arousal associated with 
jumping up. • Teach “Sit,” “Stay,” or “Place/
mat” as an alternative desirable method to 
greet people, using highly valued rewards 
(food treats, toys) in areas of the home 
where the dog is calm and tractable. • Food 
rewards should be used consistently for 
desirable outcomes. • Add the word “Stay” 
when the duration of sitting is a few 
seconds; take a step away, return to the dog, 
and give the food reward. Build up the time 
away from the dog to 3–5 minutes. • Repeat 
exercises near the door and then with leaving 
and returning. • Next ask the dog to sit for a 
food reward when returning from gradually 
longer absences. • Family members and 
familiar visitors can enter, ask the dog to sit, 
and give a food reward. • If the dog has 
difficulty sitting related to pain or discom -
fort it can be taught “Touch” for greeting. 
The “Look” cue could also help in getting a 
dog’s attention away from the person 
entering. • Dogs that like to retrieve and are 
too excited to sit may do better if a ball is 
tossed as a visitor enters.
• The owner should walk calmly to the door 
and speak in a quiet voice to avoid increasing 
the dog’s excitement. • Avoid rewarding the 
jumping with any form of attention, 
including pushing the dog off. Do not 
acknowledge or interact with the dog; hold 
arms against the body, and look away or turn 
away from the dog. The person disengaging 
from the dog facilitates the dog listening to 
an owner’s request to sit for a treat.
• Stepping on the dog’s toes, squeezing the 
paws, and any type of punishment must be 
avoided as they cause fear, may lead to 
aggression, and negatively impact the 

1362  Blackwell’s Five-Minute Veterinary Consult  
U
Unruly Behaviors: Jumping, Pulling, Chasing, Stealing—Dogs  (continued)
Pulling
• A dog’s natural walking speed may be faster 
than their owner’s. • A no-pull harness or 
head collar can be helpful and may be all that 
is needed. • A brief play session in a fenced in 
yard before a walk may decrease initial energy 
and decrease pulling (although some dogs get 
more aroused immediately after exercise).
• Pulling related to fear, anxiety, or excitement 
requires desensitization (gradual exposure) and 
training/reinforcement of an alternative 
response as discussed under Chasing below.  
• With proper application of positive 
reinforcement pulling can be resolved. • Use 
food to lure and reward the dog for walking 
next to a person. Have highly desirable small 
treats in the hand on the same side as the dog; 
initially give every few seconds. If the dog 
pulls, stop, call the dog’s name and/or ask it to 
“Look” (see Chasing), reward the behavior 
and resume walking. Over time decrease the 
frequency of giving the treat until it is every 
minute or two. Many dogs learn to come to 
the owner for a treat when they learn the 
“Look” command.  
• A second method is to stop walking as soon 
as the dog starts to pull. When the dog stops 
moving call the dog’s name and/or ask it to 
“Look” and reward the behavior and continue 
walking when the leash is slack. If the dog 
pulls again repeat the process. • All punish -
ment including leash corrections should be 
avoided as it does not train what is desirable 
and can condition fearful associations.  Sharp 
jerking or turning suddenly may cause pain 
and injury to the neck and trachea. 
Chasing
• A no-pull harness or head collar can be 
helpful in controlling the dog and reorienting 
it toward the owners in the presence of the 
chase stimulus. Herding breeds exhibit a 
phenotypic behavior that may respond better 
to control and management than to treat  - 
ment. • Dogs that chase should be desensi-
tized and counter-conditioned to the 
stimulus. • The owner should practice the 
same sit-and-stay exercises as described above, 
with the addition of a “Look” command 
using a treat brought up to the owner’s eye. 
This will help get the dog’s attention and 
focus it on the owner when it sees the moving 
stimulus. • Initially work with the dog inside 
without distractions, to train, sit, stay, and 
look. • Next work in a quiet yard with the 
dog on a leash, have the dog sit, stay, step 
away, return, look, and give the food reward. 
When the dog is successful, the process can 
be repeated in different parts of the yard with 
gradually more intense distractions.
• T raining should begin without the chase 
stimulus present. If the owner is able to keep 
the dog’s attention, the owner should then stage the chase stimulus (such as a bike or 
person jogging) to pass by at a sufficient 
distance and slow enough speed while 
training and rewarding sit, stay, and look. 
Over future sessions, the intensity of the 
stimulus can be gradually increased. • When 
the dog is able to ignore the chase stimulus in 
the yard, the owner can incorporate the same 
exercises in a park or on a walk while 
maintaining sufficient distance from the 
stimuli. When the owner sees the chase 
stimulus, he or she should ask the dog to sit, 
stay, and look, and then reward the dog.
Stealing
• The dog’s investigative behavior and 
attempts to initiate play and chase may result 
in stealing. If the result is enjoyable the 
behavior is rewarded. • Adequate attention, 
exercise, and toys before times of inattention 
(e.g., making dinner, working, watching TV) 
will help to decrease the motivation for 
stealing. • If the dog steals, the owners 
should ignore the dog, walk away, get a treat, 
and call the dog. As the dog drops the item, 
the owner can say “Drop,” “Good dog,” and 
give the dog the treat or click and treat if the 
dog is clicker trained. The dog is being 
rewarded for relinquishing the item. • The 
owner might also need to use a stay and give 
a second treat or a chew toy to be able to 
retrieve the dropped item. Another option is 
to scatter a number of treats for the dog to 
pick up while the item is removed. • If the 
dog retreats under furniture, the owner 
should not pursue. If the dog feels threatened 
or cornered, it may defend itself aggressively. 
If it is imperative that the item be retrieved, 
the client may need to lure the dog out of 
hiding with even higher value treats or offer a 
walk or favored game. The owner should 
keep a log of when and what the dog steals, 
where they were at the time, and what they 
were doing to determine when and why the 
dog is stealing. Prior to, or at these times the 
dog can be engaged in desirable alternative 
activities (social play, chews, or food-filled 
toys). In addition, the owners should 
video-record the dog to see its response 
during their absence. See separation anxiety 
for more details. • For food stealing, food 
needs to be kept out of the dog’s reach, since 
acquiring food is highly rewarding. Confine -
ment training or gating the dog out of food 
preparation and dining areas may be necessary. 
Feeding from food puzzles and toys provides 
enrichment and engages the dog in alternative 
acceptable outlets for exploration. • If the 
dog steals food because it is on a diet, a protein 
source such as plain cooked chicken or other 
meat or low-calorie foods such as raw or 
cooked vegetables can be added to help 
increase the feeling of fullness.  MEDICATIONS
None
  FOLLOW-UP
Every 2–3 weeks initially.
Close supervision, exercise, and exposure to 
varied stimuli as a young puppy and attending  
puppy classes and ongoing training can help 
to prevent and manage unruly behaviors.
Injury as a result of escaping a fence, chasing a 
stimulus, or ingesting an inappropriate item.
Generally good response to treatment for 
jumping, pulling, and stealing if the owner is 
consistent. Guidance and support of a force- 
free reward-based trainer may help to improve 
success. Chasing behaviors may be more 
difficult and resistant.
Younger dogs need more activity than many 
owners anticipate.
SEE ALSO
• Aggression—Food and Resource Guarding 
Dogs.
• LDDST = low-dose dexamethasone 
• UC:Cr = urine cortisol:creatinine ratio.
Landsberg G, Hunthausen W, Ackerman, L. 
Unruly behaviors. In: Behavior Problems of 
Elsevier Saunders, 2013, pp. 237–248.
Lindell E. Management problems in dogs. In: 
Horwitz D and Mills D. BSAVA Manual of 
Canine and Feline Behavioural Medicine. 
2nd ed. Gloucestershire, UK: BSAVA, 2009.
Author  Marsha R. Reich

Canine and Feline, Seventh Edition  1363
U
Ureterolithiasis
  BASICS
OVERVIEW
Occurrence of a urolith within a ureter; most 
originate in the renal pelvis and commonly 
occur with nephroliths. If the uroliths pass 
through the ureters into the lower urinary 
tract, patient may be asymptomatic or have 
silent hematuria. If both ureters become 
totally obstructed, without treatment death 
will occur in within 5 days.
• Breed, age, and sex predispositions vary 
with type of ureterolith.
SIGNS
• May be asymptomatic initially.
• Pain (ureteral colic) during passage of 
ureteroliths or acute ureteral obstruction.
• Renomegaly if obstruction leads to 
hydronephrosis.
• “Big kidney, little kidney syndrome”—
obstruction of one ureter has previously 
occurred, resulting in a shrunken end-stage 
kidney; signs of uremia and renomegaly occur 
due to obstruction of the remaining 
functional kidney.
• Unilateral ureteral obstruction results in 
azotemia and uremic clinical signs only when 
the contralateral kidney has reduced function.
• Signs referable to a lower urinary tract 
infection (UTI) or septicemia may be present 
with ureterolithiasis.
• Ureteral rupture may occur, resulting in 
urine accumulation in the retroperitoneum.
• Cats with distal ureteral obstruction may 
have signs of dysuria and pollakiuria.
• For a list of causes, see chapters on each 
urolith type.
• Most ureteroliths are calcium oxalate. Dogs 
may form struvite nephroliths and subsequent 
ureteroliths from urease-producing bacterial 
UTI. Cats may have ureteroliths composed of 
dried solidified blood clots.
• Circumcaval ureters (more commonly in 
right ureter) may predispose cats to obstruction 
by ureteroliths and secondary ureteral stricture 
• Prior treatment of nephroliths by extra -
corporeal shock wave lithotripsy (ESWL) or 
medical dissolution may be additional risk 
factors.
  DIAGNOSIS
• Consider in cases of acute kidney injury 
(AKI), rapid progression of chronic kidney disease (CKD), renomegaly, abdominal pain, 
or fluid accumulation in the retroperitoneal 
space. Obstruction to urine outflow of both 
kidneys may not produce the same magnitude 
of renomegaly as unilateral obstruction 
because the patient may succumb to uremic 
complications before severe dilation occurs.
• Radiopacities detected by abdominal 
radiography that may be confused with 
ureteroliths include fecal material in the 
colon, nipples, peritoneoliths, calcified 
lymph nodes, and mineralization of the 
renal pelvis.
• Radiolucent ureteroliths may be difficult to 
differentiate from blood clots. Other causes of 
ureteral obstruction include intraluminal 
tumors, ureteroceles, ureteral strictures, and 
extraluminal compression. Hydroureter and 
hydronephrosis may occur because of ureteral 
ectopia, pyelonephritis, ureterovesical 
stenosis, and obstruction of the ureteral 
opening at the trigone (most commonly due 
to urothelial carcinoma).
CBC in patients with pyonephrosis secondary 
to obstructive ureteroliths may have 
leukocytosis, immature neutrophilia, and 
thrombocytopenia. Ionized calcium 
concentration, urinalysis, and urinary 
excretion of electrolytes may permit 
estimation of urolith composition pending 
results of definitive analysis.
• Submit all retrieved ureteroliths for 
quantitative analysis to determine appropriate 
preventive strategies.
• Blood pressure should be monitored; 
hypertension is common with CKD or AKI 
secondary to ureteral obstruction.
IMAGING
• Radiography—radiopaque ureteroliths 
may be visualized. If obstruction and 
hydronephrosis have occurred, renomegaly 
may be apparent. If ureteral rupture occurs, 
contrast in the retroperitoneal space may be 
lost. Small ureteroliths may not be visualized.
• Ultrasonography—valuable for detecting 
hydronephrosis or hydroureter. Changes 
suggesting pyelonephritis may also be 
detected by ultrasound. The dilated proximal 
ureter may be traced to the ureteroliths. 
Ureteroliths are not observed ultrasono -
graphically in up to 25% of cats with 
ureteroliths. Ultrasound-guided pyelocentesis 
can be used to confirm ureteral obstruction, 
although this is usually performed during 
surgical placement of subcutaneous ureteral 
bypass (SUB) or ureteral stents.
• CT before and after IV contrast can be used 
to confirm obstructive ureteroliths if they are 
suspected but not confirmed by other 
imaging modalities. This is not required for 
surgical planning for SUB or stent placement.DIAGNOSTIC PROCEDURES
Nuclear scintigraphy alone should not be 
used to determine whether or not to preserve 
or surgically remove a kidney.
Progressive dilation of the pelvis and calyces; 
in advanced cases, the kidney may be 
transformed into a thin-walled sac with only 
shell of atrophic cortical parenchyma; ureteral 
dilation proximal to the site of obstruction is 
often present.
  TREATMENT
• For small nonobstructive ureteroliths, 
allowing time for the ureteroliths to 
spontaneously pass down the ureter to the 
bladder may eliminate the need for intervention.
• Remove or bypass ureteroliths that are 
causing obstruction.
• Ureteroliths in dogs have been successfully 
treated with ESWL. Efficiency of ESWL 
fragmentation of ureteroliths is improved 
with prior ureteral stent placement. Calcium 
oxalate uroliths from cats are intrinsically 
resistant to fragmentation via ESWL. ESWL 
is not recommended for cats.
• Surgical techniques recommended for 
removal of ureteroliths vary, depending on 
the site of obstruction, species, the presence 
or absence of UTI, and the degree of function 
of the associated kidney.
• SUB placement is effective for relief of 
ureteral obstruction in cats and is often the 
preferred surgical procedure for cats.
• Ureteroneocystotomy may be performed for 
ureteroliths in the middle and distal ureter: 
the ureter proximal to the obstruction is 
excised and reimplanted into the bladder. 
Ureteroliths in the proximal ureter may be 
removed by ureterotomy. Performance of 
ureterotomy or ureteroneocystotomy in cats 
requires microsurgical expertise. When the 
contralateral kidney functions normally and 
severe end-stage hydronephrosis is present, 
ureteronephrectomy may be appropriate.
• Ureteral stent placement to bypass 
obstructive ureteroliths relieves the 
obstruction and causes passive ureteral 
dilation. Ureteral stents may be placed 
endoscopically in dogs and surgically in dogs 
and cats. Ureteral stent combined with 
medical dissolution effectively resolves 
struvite ureteroliths in dogs.
• Medical dissolution is only effective for 
struvite ureteroliths when combined with

1364  Blackwell’s Five-Minute Veterinary Consult  
U
ureteral stent placement. Medical dissolution 
requires culture-guided antibiotics and 
dissolution diet.
• Therapy aimed at prevention of recurrent 
disease is imperative following relief of 
Attempts to prevent one type of urolith may 
promote formation of a second type.
  FOLLOW-UP
• Following SUB placement, routine 
sampling of the SUB for urinalysis and 
culture along with flushing the SUB is 
performed every 3 months.
• Instillation of tetra-EDTA solution into the 
SUB is recommended with SUB flushes.
• Following successful removal of 
ureteroliths, recheck every 3–6 months for 
recurrence of uroliths and to ensure owner 
compliance with preventive measures; 
urinalysis, imaging, and urine culture.PREVENTION/AVOIDANCE
• Elimination of predisposing factors.
• Specific therapy depends on the mineral 
composition of the urolith.
Hydronephrosis, CKD, AKI, recurrent UTI, 
pyelonephritis, sepsis, ureteral rupture, 
ureteral stricture, hypertension.
Highly variable; if unilateral disease is 
present, the opposite kidney retains adequate 
function, and recurrence is prevented, the 
prognosis is good. Prognosis is good for cats 
with SUB or ureteral stent placement that 
recover renal function to stage 1–2 CKD. 
Prognosis is good for dogs with obstructive 
ureteroliths that recover renal function to 
stage 1–2 CKD.
• AKI = acute kidney injury
• ESWL = extracorporeal shock wave lithotripsy.• SUB = subcutaneous ureteral bypass.
Berent AC, Weisse CW, Bagley DH, et al. 
Use of a subcutaneous ureteral bypass device 
for treatment of benign ureteral obstruction 
in cats: 174 ureters in 134 cats (2009-2015. 
J Am Vet Med Assoc 2018, 
253:1309–1327.
Berent AC, Weisse CW, Todd K, et al. 
Technical and clinical outcomes of ureteral 
stenting in cats with benign ureteral 
obstruction: 69 cases (2006–2010). J Am 
Vet Med Assoc 2014, 244:559–576.
Kuntz JA, Berent AC, Weisse CW, et al. 
Double pigtail ureteral stenting and renal 
pelvic lavage for renal-sparing treatment of 
obstructive pyonephrosis in dogs: 13 cases 
(2008–2012). J Am Vet Med Assoc 2015, 
246:216–225.
Consulting Editor  J.D. FosterUreterolithiasis  (continued)

Canine and Feline, Seventh Edition  1365
U
Urethral Prolapse
  BASICS
OVERVIEW
• Prolapse of the mucosal lining of the distal 
urethra through the external urethral orifice.
• Prolapsed urethra appears as a congested, 
pea-shaped mass protruding from the distal 
end of the penis and is often associated with 
hemorrhage. Excessive licking may result in 
further traumatic damage to the exposed 
urethral mucosa.
• Reported in male dogs and extremely rare 
in male cats.
• Most common in English bulldog, Boston 
terrier, and Yorkshire terrier.
• Mean age 18 months; range 4 months–5 
years.
SIGNS
• Intermittent or persistent bleeding from the 
urethra.
• Intermittent or persistent licking of penis.
• Dysuria and pollakiuria caused by 
concomitant disorders.
• Persistent or intermittent urethral prolapse.
• Pale mucous membranes if anemic.
• Necrosis of the prolapsed urethra secondary 
to drying or self-induced trauma from licking.
• Uroliths may be palpable in the urinary 
bladder or urethra.
• May result from sexual excitement and/or 
unrelated disorders (e.g., infections, uroliths, 
neoplasia) of the lower urinary tract.
• Increased intra-abdominal pressure secondary 
to dysuria associated with urocystoliths.
• Proposed causes include abnormal 
development of the urethra with increased 
intra-abdominal pressure as a consequence of 
brachycephalic airway syndrome, dysuria, or 
sexual activity. Increased intra-abdominal 
pressure could impair venous return of blood 
through the pudendal veins, predisposing 
susceptible dogs to engorgement of the corpus 
spongiosum surrounding the distal urethra.
• Breed predisposition (bulldogs and Boston 
  DIAGNOSIS
• Persistent penile frenulum.
• Fracture of the os penis.
• Urethroliths.
• Urethral neoplasia.CBC/BIOCHEMISTRY/URINALYSIS
• CBC—may reveal regenerative anemia.
• Serum biochemistries—usually normal.
• Hematuria may be absent in urine collected by 
cystocentesis, but present in voided urine.
• Urine culture and sensitivity.
Coagulation profile may rule out coagulopathy.
IMAGING
• Survey radiographs—useful to find some 
uroliths and evaluate the prostate size.
• Contrast cystourethrography—useful to 
rule out radiolucent uroliths, urethral 
disorders, and prostatic disease.
• Abdominal ultrasonography—useful to 
evaluate the prostate and urinary bladder.
• Ejaculation—useful to evaluate urethra 
during penile erection; some urethral prolapses 
are present only during penile erection.
• Evaluation of ejaculate may show evidence 
of prostatic disease.
• Enlarged images obtained with a surgical 
microcamera associated with a flexible 
endoscope may be necessary to diagnose 
urethral prolapse in cats.
  TREATMENT
• May not be required if asymptomatic or 
only associated with episodic bleeding.
• If present only during penile erection, consider 
castration prior to attempting surgical removal of 
prolapsed tissue; diethylstilbestrol given for 3–6 
weeks after surgery may reduce frequency of 
erections. If cause is unknown, castration status 
may not affect prolapse recurrence.
• Consider surgery for patients with excessive 
bleeding, pain, or extensive ulceration or 
necrosis of the prolapsed tissue, or if 
refractory to medical management.
• Satisfactory results have been obtained by 
manual reduction of the prolapse followed by 
urethropexy.
• CO2 laser surgical technique may improve 
hemostasis, visualization, and accuracy of the 
surgeon, and decrease postoperative swelling.
• A surgical microscope may be necessary for 
adequate visualization to perform urethro -
plasty in cats.
• Postoperative hemorrhage and prolapse 
recurrence may be reduced with a simple 
continuous suture pattern and administration 
of postoperative sedation.
• Bacterial urethritis warrants use of 
appropriate antibiotics.• Consider using diethylstilbestrol for 3–6 
weeks after surgery to reduce frequency of 
erections.
Consider risk of bone marrow suppression before 
giving estrogens, especially in anemic patients.
  FOLLOW-UP
Reevaluate 7–10 days following surgery for 
hemorrhage or recurrence of urethral prolapse.
If urethral prolapse is associated with penile 
erection, prevent contact with female dogs or 
situations likely to cause erection.
• Most common postoperative complication 
was hemorrhage (39%).
• Prolapse recurred in 57% of dogs, but was 
less common when postoperative butorphanol 
or acepromazine were given.
• Recurrence of the prolapse may occur, 
especially if an underlying cause has not been 
detected and eliminated or controlled.
• Prolapse may persist without significant 
sequelae. Some dogs may not require 
therapy.
• Some may not have problems after castration 
and/or surgical correction of a prolapsed urethra.
Urolithiasis and urinary tract infection.
Carr GC, Tobias KM, Smith L. Urethral 
prolapse in dogs: a retrospective study. Vet 
Surg 2014, 43(5):574–580.
Fossum TW. Urethral prolapse. In: Small 
Animal Surgery, 3rd ed. St. Louis, MO: 
Mosby Elsevier, 2007, pp. 687–689.
Kirsch JA, Hauptman JG, Walshaw RA. 
Urethropexy technique for surgical 
treatment of urethral prolapse in the male 
dog. J Am Anim Hosp Assoc 2002, 
38:381–384.
Osborne CA, Sanderson SL. Medical 
management of urethral prolapse in male 
dogs. In: Bonagura JD, Kirk RW, eds., 
1027–1029.
Author  Sherry Lynn Sanderson

1366  Blackwell’s Five-Minute Veterinary Consult  
UUrinary Retention, Functional
 BASICS
Failure of the urethral smooth and/or striated 
muscle relaxation as the detrusor muscle 
contracts at the beginning of urination. 
Thought to be due to dysfunction of the 
reflex arc allowing urethral sphincter 
relaxation as the detrusor muscle contracts at 
the beginning of urination.
This is a disorder of the emptying phase of 
micturition due to functional obstruction of 
the outflow tract and urethra. While the 
pathophysiology is not completely under-
stood, it is thought that the neurologic lesion 
is located within the reticulospinal tract, 
Onuf nucleus, or caudal mesenteric ganglion. 
The loss of inhibitory signals to the pudendal 
and hypogastric nerves may also be involved. 
Involvement of a more local lesion (peripheral 
nerves, neuromuscular junction, striated and 
smooth muscles of the sphincters, etc.) is 
unknown. It is unclear whether anxiety and 
other behavior disorders may contribute to 
the disorder.
• Urinary tract.
• Typically have otherwise normal neurologic 
Unknown. The literature suggests increasing 
incidence which may be related to increased 
awareness and thus diagnosis in male dogs.
Dogs (cats can be affected). Most common in 
middle-aged male dogs (mean age of 4.9 
years). Females are also affected although 
rarely. Large- to giant-breed dogs most 
CAUSES
• Neurologic dysfunction due to spinal cord 
lesions cranial to the sacral segment resulting in 
upper motor neuron bladder signs with 
simultaneous detrusor and urethral contraction.
• Damage to the reflex arc impairing urethral 
sphincter relaxation during detrusor contraction.
• Urethral spasm of the smooth or striated 
muscles.
• Controversial behavioral/anxiety-driven 
component in some patients.
• Large- to giant-breed dogs (25–64 kg).
• Young adults.
• Intact males—sexual excitement in the 
presence of intact females.
• Cauda equina syndrome.
• Urinary tract infections or urethritis 
resulting in urethral spasm.
• Surgery in the area of the bladder neck.
• Urethral and prostatic tumors.  DIAGNOSIS
• Diagnosis of a functional urethral obstruc-
tion is presumptive. These animals exhibit a 
typical pattern of urination in which they 
often start with a normal stream that quickly 
weakens and may stop completely. The 
affected animal may posture multiple times 
attempting to urinate without ever fully 
emptying their bladder. A large residual urine 
volume (>1 mL/kg) is typically noted. A 
mechanical obstruction should be ruled out; 
passing a urinary catheter is typically easy in 
dogs with functional obstruction.
• As a result of urine retention, overflow 
incontinence may occur. This can make it 
difficult for owners to distinguish it from 
storage disorders (e.g. urethral sphincter 
mechanism incompetence).
• This condition can share some similarities 
with upper motor neuron bladders seen in 
dogs with intervertebral disc disease.
• Other causes of urine obstruction must be 
ruled out. These include urolithiasis, 
neoplasia, benign prostatic hyperplasia, 
prostatitis, foreign body, and urethral 
Typically unremarkable though evidence of 
urinary tract infections may be noted on the 
urinalysis (pyuria, bacteriuria).
None
IMAGING
Contrast urethrography studies in these dogs 
are often normal, though narrowing of the 
urethra may be noted due to urethrospasm. 
Ultrasound can be used to assess the ureters 
and renal pelvises to look for dilation 
secondary to obstruction from urolithiasis or 
vesicoureteral reflux.
Dogs with functional urethral obstruction are 
typically easily catheterized. A large residual 
urine volume is typically noted. A normal 
residual urine volume in dogs is 0.1–3.4 mL/
kg (0.2 mL/kg mean). Urethroscopy may be 
indicated in individuals that fail to respond to 
medical therapy. This will allow for identifica-
tion of strictures or other anatomic abnor-
malities. Urodynamic evaluation does not 
typically show increased urethral pressure 
unless the animal is actively voiding.
 TREATMENT
T reatments are directed at addressing the 
relaxation of the smooth and striated muscles 
of the urethral sphincter (see drugs listed under Medications). Owners can also be instructed 
how to intermittently pass sterile catheters at 
home to address residual urine volume. If 
present, urinary tract infections should be 
treated based on culture and susceptibility 
testing. In cases of chronic functional urethral 
obstruction, bladder atony may occur 
secondary to prolonged bladder distension. In 
these cases treatment of bladder atony may be 
necessary. This should only be initiated once 
the functional obstruction has been relieved. 
Urethral stenting and cystostomy tubes are 
considered a salvage procedure and should 
only be considered in the most refractory cases. 
Intact males should be castrated.
• Alpha-1 adrenergic antagonists (give on an 
empty stomach):
◦  Prazosin 0.5 mg/kg PO q12h; 
1 mg/15 kg PO q8–12h.
◦  Tamsulosin 0.1 mg/10 kg PO q24h; 
0.4 mg/dog PO q24h (may increase to q12h).
• Benzodiazepines (anxyiolytic and muscle 
relaxant):
◦  Diazepam 2–10 mg/dog PO q8h.
• Phenothiazine sedative/tranquilizer:
◦  Acepromazine maleate 0.55–2.2 mg/kg 
PO q6–12h.
• Muscle relaxant:
◦  Methocarbamol 132 mg/kg/day PO 
divided q8–12h, then 61–132 mg/kg/day 
divided q8–12h. If no response in 5 days, 
discontinue.
• Cholinergic:
◦  Bethanechol chloride 2.5–25 mg/dog 
q8h (some respond to q12h).
• Pro-motility agent:
◦  Cisapride 0.1–0.5 mg/kg PO q12h (up 
to 1 mg/kg PO q8h).
• Behavioral modification agents and 
anxiolytics may also provide some benefit.
• Alpha-agonists.
• Testosterone or other androgens—avoid 
anything that may result in increased prostate  
size.
• Do not administer any medications that 
will promote detrusor muscle activity (i.e., 
bethanechol) until urethral obstruction 
(functional or mechanical) has been relieved.
• Prazosin may cause hypotension, CNS signs 
such as lethargy or dizziness, weakness, syncope, 
and gastrointestinal upset.
• Tamsulosin may cause hypotension though 
the safe dosage range is quite wide and severe 
hypotension is less likely than with other drug 
choices.
• Acepromazine may cause sedation and 
hypotension as well as cardiovascular collapse

Canine and Feline, Seventh Edition  1367
U(continued)  Urinary Retention, Functional
from bradycardia and hypotension, decreased 
tear production may occur in cats.
• Diazepam can cause sedation, increased 
appetite, changes in behavior such as 
agitation or aggression have been reported. 
Dogs may also show ataxia. Avoid use in cats 
due to risk of liver toxicity.
• Methocarbamol may cause sedation, 
increased salivation, vomiting, along with 
lethargy, weakness and ataxia.
• Bethanechol’s adverse effects are typically 
minimal when administered orally. Gastro -
intestinal effects such as hypersalivation, 
vomiting, diarrhea and anorexia may be seen 
but are typically mild. Cardiovascular and 
respiratory effects unlikely with oral dosing.
• Cisapride may cause vomiting, abdominal 
discomfort or diarrhea. The cardiovascular 
effects seen in humans are not documented in 
• Prazosin should not be used in conjunction 
with beta-blockers, sildenafil, or verapamil/
nifedipine due to concerns for increased risk 
of hypotension.
• Tamulosin should not be used with other 
alpha-1 adrenergic antagonists or sildenafil/
tadalafil as they may have cumulative hypo  - 
tensive effects. Cimetidine, charithromycin, 
erythromycin, ketoconazole, and terbinafine 
may all result in increased plasma levels of 
tamulosin.
• Acepromazine may have adverse effects 
when administered in conjunction with a 
number of drugs. Be careful when administering with other drugs that may 
cause CNS effects or hypotension.
• Diazepam should be used with caution 
when administered concurrently with other 
CNS-depressant medications. There are also 
several classes of drugs that may increase or 
decrease plasma levels of diazepam when 
• Methocarbamol should be used with 
caution when other CNS-depressant 
medications are also prescribed.
• Bethanechol should not be used with other 
cholinergic or anticholinergic medications 
due to synergistic or antagonistic effects, 
• Cisapride’s effects may be decreased when 
given with anticholinergics. When given with 
benzodiazepines the sedative effects may be 
enhanced.
 FOLLOW-UP
Monitoring of residual urine volume as well 
as routine screening for urinary tract 
infections should be performed.
If left untreated, chronic bladder distension 
can result in bladder atony and dysfunction 
of the detrusor muscle. Urine retention puts 
these dogs at risk of developing urinary tract 
infections. MISCELLANEOUS
Castrate male dogs.
SYNONYMS
• Detrusor-urethral dyssynergia.
• Detrusor-sphincter dyssynergia.
Bloch F , Pichon B, Bonnet AM, et al 
Urodynamic analysis in multiple system 
atrophy: characterization of detrusor-
sphincter dyssynergia. J Neurol 2010, 
257:1986–1991.
Byron JK. Micturition disorders. Vet Clin 
Small Anim 2015, 45:769–782.
Diaz Espineira, MM, Viehoff FW, Nickel RF . 
Idiopathic detrusor-urethral dyssynergia in 
dogs: a retrospective analysis of 22 cases. 
J Small Anim Pract 1998, 39:264–270.
Lane I, Fischer JR, Miller E, et al. Functional 
urethral obstruction in 3 dogs: clinical and 
urethral pressure profile findings. J Vet 
Intern Med 2000, 14:43–49.
Authors  William M. Cole and Julie K. Byron

1368  Blackwell’s Five-Minute Veterinary Consult  
UUrinary Tract Obstruction
  BASICS
Restricted flow of urine from the kidneys 
through any point of the urinary tract to the 
external urethral orifice.
 PATHOPHYSIOLOGY
Physical or functional obstruction of the 
urinary tract resulting in partial or complete 
cessation in renal excretory function. Luminal 
pressure is transmitted to the level of the 
kidney and its functional units (nephrons). As 
tubular pressure exceeds filtration pressure, 
glomerular filtration rate (GFR) ceases. 
Pathophysiologic consequences depend on 
site, degree, and duration of obstruction. The 
resulting uremia, acidemia, and hyperkalemia 
creates the clinical signs and progression.
• Cardiovascular, nervous, and respiratory 
systems also affected relative to duration of 
obstruction and severity of metabolic 
derangement.
• More common in males than females.
SIGNS
• Pollakiuria and stranguria.
• Diminished to absent urine stream.
• Vocalizing, frequent trips to the litter box 
(cats).
• Gross hematuria.
• Systemic signs associated with complete (or 
nearly complete) urinary tract obstruction—
lethargy, reduced appetite, and vomiting.
• Excessive (i.e., overly large or turgid) or 
inappropriate (i.e., remains after voiding 
efforts) distended urinary bladder, 
especially in conjunction with lower 
urinary tract signs.
• Abdominal distention/discomfort.
• Uroliths maybe be palpable in the distal 
urethra of obstructed male dogs, or on rectal 
exam of female dogs.
• Signs of severe uremia—dehydration, 
weakness, hypothermia, and/or bradycardia 
with moderate hyperkalemia, altered 
mentation, or sinus tachycardia from pain/
stress.
CAUSES
Intraluminal Causes
• Urolithiasis—most common in male dogs.
• Urethral plugs—most common in male 
cats.
• Idiopathic—no overt intraluminal physical 
obstruction; may involve functional 
obstruction.Intramural Causes
• Neoplasia of the bladder neck or urethra—
more common in dogs.
• Prostatic disorders (neoplasia, prostatitis, 
etc.) in male dogs.
• Edema, hemorrhage, or spasm at sites of 
obstruction and/or associated with inflammation. 
Can contribute to persistent or recurrent 
obstruction following catheterization.
• Stricture at a site of prior injury or 
• Ruptures, lacerations, and punctures—
usually caused by traumatic incidents.
Miscellaneous Causes
• Displacement of the urinary bladder into a 
perineal hernia.
• Neurogenic (see Urinary Retention, 
Functional).
• Urolithiasis, particularly in males.
• Feline lower urinary tract disease, 
particularly in males.
• Prostatic disease in male dogs.
  DIAGNOSIS
• Owners may have difficulty distinguishing 
urinary obstruction from constipation.
• Signs of feline idiopathic cystitis can be 
difficult to distinguish from obstruction, 
especially if there are no signs of systemic 
illness. Determination of bladder size (large/
firm with obstruction, small with cystitis) can 
help distinguish.
• Animals whose urinations are not routinely 
observed by owners can present for signs 
referable to systemic illness rather than 
concern for obstruction.
• Evaluation of any azotemic patient, in 
conjunction with history and physical exam, 
should include consideration of possible 
postrenal causes (e.g., urinary obstruction).
• Hemogram is usually normal; a stress 
leukogram or hemoconcentration may be 
seen.
• Biochemical analysis may reveal azotemia, 
hyperkalemia, and hypocalcemia proportional 
to duration of obstruction.
• Hematuria and proteinuria are common. 
Crystalluria may be associated with urolithiasis, 
though can be present in the absence of stones. 
There may be evidence of bacteriuria (dogs) 
and pyuria. Atypical epithelial cells may be 
seen in patients with neoplasia.
• Urine culture may be beneficial if suspicion 
for urinary tract infection (UTI) in 
obstructed dogs (especially secondary to 
uroliths). Obstructed cats are unlikely to have bacterial cystitis, and presenting urine culture 
is not recommended unless recently 
catheterized.
• Uroliths passed or retrieved should be sent 
for crystallographic analysis.
IMAGING
• Uroliths—often demonstrated by survey 
radiography; but may be missed because of 
their size, composition, or location. Ensure 
entire lower urinary tract is included.
• Positive- or double-contrast cystourethro -
graphy may detect lesions of the urethra and 
urinary bladder.
Ultrasonography is highly sensitive in 
detecting lesions of the bladder, proximal 
urethra, prostate, and upper urinary tract.
• Electrocardiography may detect 
abnormalities due to hyperkalemia, including 
tall T waves, prolonged PR interval, widened 
QRS complexes, loss of P waves, and brady  - 
cardia.
• T ransurethral catheterization and contrast 
studies may determine the location and 
nature of obstructing material. Animals that 
cannot urinate despite being readily 
catheterized likely either have intramural 
lesions or functional urinary retention.
• Cystoscopy can be helpful to identify 
lesions not observed on contrast study or 
  TREATMENT
• Complete obstruction is a medical 
emergency that can be life-threatening; 
treatment should be started immediately.
• Initial goals are addressing metabolic 
derangements, especially significant hyper -
kalemia, and establishing urinary patency.
based on degree of cardiovascular compromise, 
dehydration, and potential for post-obstructive 
diuresis.
• Severe hyperkalemia (K+ >8 mmol/L, 
significant bradycardia/ECG changes)—
administer calcium gluconate (1 mL/kg over 
3–5 minutes, titrated based on ECG 
changes), regular insulin 0.1–0.2 U/kg IV 
once, and 50% dextrose bolus 1 mL/kg IV, 
diluted, over 5 minutes. May need continued 
dextrose infusion (2.5–5%) for 4–6 hours to 
avoid hypoglycemia. Terbutaline 0.01 mg/kg 
IM or IV can also be given. For more severe 
derangements (K+ >10 mmol/L, pH <7.1) 
consider sodium bicarbonate 1 mL/kg IV 
over 5–10 minutes.
• Decompressive cystocentesis may allow 
relief of intravesicular pressure, resumption of 
GFR, and decreased back-pressure for

Canine and Feline, Seventh Edition  1369
Ucatheterization. Based on available studies, 
risk of complications appears to be very low.
• Urethral catheterization under heavy 
sedation or general anesthesia (see below) to 
relieve physical obstruction and establish 
urethral patency.
• Flushing urinary bladder until clear 
effluent, attach to sterile collection system.
• Post-obstructive management geared 
toward nursing care, maintaining fluid 
balance, correction of metabolic 
derangements, and sedation/analgesia.
• Rate of fluid administration should be 
determined based on clinical picture. Some 
patients can experience a post-obstructive 
diuresis, with significant urinary losses. It is 
important to keep up with these losses to 
avoid dehydration. This can be achieved by 
matching fluid rate to urine output.
• Hyperkalemia should resolve within hours 
after de-obstruction, and potassium may 
eventually need to be supplemented. 
Azotemia should also significantly decrease 
within 12–24 hours.
• Patients with obstructive urolithiasis often 
require a separate procedure for stone 
removal.
• Sedation/analgesia/anesthesia for catheter 
placement should be dictated by patient 
stability. Acepromazine plus an opioid if 
stable; opioid plus benzodiazepine if unstable. 
Ketamine and a benzodiazepine is a common 
combination. Alfaxalone may also be 
considered. General anesthesia may be 
indicated as it gives the most urethral 
relaxation, especially for obstructed dogs.
• In the post-obstructive period, continued 
sedation and analgesia is beneficial.
• Urethral relaxants (e.g., acepromazine and/
or prazosin) may be beneficial for post-
obstructive cats or patients with neurogenic 
urine retention.
• Antibiotics may be indicated with strongly 
suspected or documented evidence of 
infection (such as cytology or positive 
culture). Antibiotics should not be 
administered to prevent UTI while a urinary 
catheter is in place. This is not effective and can promote bacterial resistance.
• Nonsteroidal anti-inflammatory drugs have 
failed to improve speed of resolution or the 
frequency of reobstruction.
• Corticosteroids are contraindicated while a 
urinary catheter is in place. This can 
predispose to the development of UTI.
• Nonsteroidal anti-inflammatory 
medications should be initially avoided in 
more metabolically compromised patients.
Avoid drugs that reduce blood pressure (e.g., 
acepromazine) or induce cardiac dysrhythmia 
(e.g., ketamine) until dehydration and 
hyperkalemia are resolved. Avoid excessive 
force during catheterization attempts.
  FOLLOW-UP
• Continuous ECG monitoring to guide 
treatment and evaluate response is warranted 
if there were significant changes initially.
• Assess urine production and hydration 
status frequently, and adjust fluid 
administration rate accordingly.
• Monitor renal values and electrolytes. 
Sicker patients may require more frequent 
monitoring (q6–12); once daily for more 
stable patients.
• The urinary catheter can be removed once 
metabolic derangements and urine output has 
normalized, and the urine appears to be clear 
of gross debris, clots, etc.
• After urinary catheter removal, monitor 
ability to urinate closely for at least 
12–24 hours.
• Cats may benefit from continued pain 
medication and urethral relaxation for 5–7 days 
at home, as well as recommendations (increased 
water intake, environmental enrichment) to 
help decrease risk of re-obstruction.
• Death.
• Injury to the excretory pathway 
(e.g., urethral tear) while trying to relieve 
• Hypokalemia during post-obstructive 
diuresis.• Recurrence of obstruction (estimated at 
15–40%).
• Bradycardia secondary to hyperkalemia.
SYNONYMS
Urethral obstruction.
SEE ALSO
Disease.
Cooper ES. Controversies in the management 
of feline urethral obstruction. J Vet Emerg 
Crit Care 2015, 25(1):130–137.
Cooper ES. Feline lower urinary tract 
obstruction. In: Drobatz KJ, Hopper K, 
Rozanski E, Silverstein DC, eds., Textbook 
Hoboken, NJ: Wiley, 2019, pp. 634–640.
Gerber B, Eichenberger S, Reusch CE. 
Guarded long-term prognosis in male cats 
with urethral obstruction. J Feline Med 
Surg 2008, 10:16–23.
Hall J, Hall K, Powell LL, et al. Outcome of 
male cats managed for urethral 
obstruction with decompressive 
cystocentesis and urinary catheterization: 47 
cats (2009–2012). J Vet Emerg Crit Care 
2015, 25(2):256–262.
Segev G, Livne H, Ranen E, et al. Urethral 
obstruction in cats: predisposing factors, 
clinical, clinicopathological characteristics 
and prognosis. J Feline Med Surg 2011, 
13:101–108.
Author  Edward S. Cooper
available online(continued)  Urinary Tract Obstruction

1370  Blackwell’s Five-Minute Veterinary Consult  
UUrinary Tract Parasites
  BASICS
OVERVIEW
Dioctophyma renale (Giant Kidney 
Worm)
In North America, cases are frequently 
encountered in Mississippi, Louisiana, 
Minnesota, Wisconsin, Michigan, and the central 
and eastern provinces of Canada. Humans are 
accidental hosts; because of the aquatic portion of 
its life cycle, water is an essential element of the 
habitat of D. renale . Minks are the most 
commonly infected mustelids, and are the 
principal definitive host in North America.
Life Cycle
• To complete the life cycle, both males and 
females must be located in the same kidney of 
the host, and the urinary tract must be the 
patent. Fertile eggs are passed with urine 
voided by the host, and then embryonate in 
water. First-stage larvae are produced after 1–7 
months. The definitive hosts become infected 
by ingesting the infective larvae in annelids.
• Definitive hosts are infected by ingesting raw 
fish, frogs, other paratenic hosts, or Lumbriculus 
variegatus . After ingestion, the infected larvae 
penetrate the walls of the stomach or intestines 
and migrate to the submucosa. After approxi -
mately 5–7 days, they migrate to the liver and 
remain there for about 50 days. Migration to 
the right or the left kidney and invasion of the 
renal pelvis follows.
• D. renale  have been found more frequently 
in the right kidney than in the left. Finding 
encysted D. renale  around liver is associated 
with larval penetration at the lesser curvature 
of the stomach. On occasion, D. renale  have 
been encountered in the urinary bladder and/
or ureters. Infective larvae become mature 
gravid females in the definitive host after 
3.5–6 months. The entire life cycle requires 
approximately 2 years.
Pathophysiology in the Kidney
• Adult parasites have attained substantial size 
by the time they penetrate the kidney. The 
exact mechanisms involved with gaining 
access to the renal pelvis is unknown, but 
probably results from the effects of enzymes 
released by the parasite.
• Available evidence does not support the 
theory that adult D. renale  slowly devour the 
renal tissue of the host, reducing it to a 
hollow sack. Although the exact 
mechanism(s) of destruction is not known, 
obstruction caused by the growing adult 
parasite(s) and secondary hydronephrosis (or 
pyonephrosis) plays a major role. 
Examination of the kidneys from dogs with 
unilateral renal infection reveals changes 
typical of advanced hydronephrosis (i.e., 
obliteration of the majority of renal tubules 
surrounded by chronic inflammatory tissue and persistence of the structural architecture 
of many glomeruli).
• Ova of D. renale  may be observed in the 
renal parenchyma adjacent to the renal pelvis. 
The urothelium lining the renal pelvis is often 
hyperplastic.
• If only one kidney is affected with D. 
renale  the host retains adequate renal 
function due to compensatory hypertrophy 
and hyperplasia of the remaining kidney. If 
both kidneys are parasitized, or if one kidney 
is parasitized and the opposite kidney has 
substantial comorbid dysfunction, varying 
stages of renal failure and uremia may occur. 
Eggs that are released by female worms pass 
through the urinary tract and provoke 
inflammation in the mucosa of the ureter 
and urinary bladder.
Pathophysiology in the Peritoneal Cavity
• In dogs, viable parasites located in the 
abdominal cavity and/or between lobes of the 
liver have been incidental findings during 
ovariohysterectomy.
• Eggs present in the peritoneal cavity can 
trigger development of chronic peritonitis. 
Examination of the abdominal viscera from 
dogs with D. renale  in the peritoneal cavity 
revealed hemorrhage, granulomatous 
inflammation, and fibrosis frequently 
involving the omentum, the surface of the 
liver, and the surface of the spleen. Viable 
adult males have been found in the peritoneal 
cavity of dogs without an associated 
• Ascites may occur in dogs with peritoneal 
D. renale  colonization. The fluid detected in 
the abdominal cavity is usually hemorrhagic.
Pearsonema (Capillaria)
• Pearsonema  and Capillaria  are used 
interchangeably and appear to be identical in 
taxonomy and biologic behavior.
• Pearsonema (Capillaria) plica  are small, 
thread-like, yellowish parasites that invade the 
mucosa or submucosa of the bladder and 
rarely the renal pelvis and ureter, causing a 
mild inflammatory response.
• P . plica  in dogs and cats and P . feliscati  in 
cats have been uncommonly associated with 
signs of lower urinary tract disease.
• P . plica  passes ova with bipolar plugs in urine. 
When earthworms ingest embryonated ova, the 
parasite develops into the infective stage. 
Ingestion of an infective earthworm results in a 
patent infection in dogs in 58–88 days.
• The life cycle of P . feliscati  is poorly 
understood.
D. renale
Pearsonema
• Dogs—no predilection reported.
• Cats—affected cats almost always >8 
months old.SIGNS
D. renale
• Feeding L. variegatus  infected with D. renale  
to dogs typically induces vomiting due to 
effects of the parasite on the gastric mucosa.
• If only one kidney has been invaded with 
D. renale , signs are often absent.
• Silent hematuria may be the first indication 
of an abnormality.
• Palpation of the abdomen may reveal an 
enlarged and/or misshapen hydronephrotic 
kidney.
• If both kidneys are parasitized, clinical signs 
attributable to renal failure or uremia may 
occur. The host will typically die before 
extensive hydronephrosis of both kidneys has 
time to develop. The degree of renal dysfunc -
tion is influenced by (1) number of parasites 
in the kidney, (2) duration of infection, (3) 
number of kidneys parasitized, and (4) presence 
and severity of comorbid renal disease.
• Pollakiuria, hematuria, stranguria, and 
dysuria in heavily infected animals.
D. renale
See Overview.
Dogs
• High prevalence of infection (up to 50%) 
in the natural hosts (e.g., foxes, raccoons) in 
the southeastern United States may 
predispose animals in this geographic region.
• In kennels, high infection rates associated 
with contaminated soil surfaces.
Cats
Rare in United States; infection prevalence of 
18–34% is reported in Australia.
  DIAGNOSIS
D. renale
Any cause of hydronephrosis or renomegaly.
Consider other, more common causes of 
lower urinary tract disease, such as 
urolithiasis, urinary tract infection, trauma, 
D. renale
• When gravid female worm is present in the 
kidney that has a patent track to the exterior, 
microscopic examination of urine usually 
reveals ova of D. renale .
• Hematuria, pyuria, and proteinuria with or 
without eggs are indicative of an inflamma-
tory response.

Canine and Feline, Seventh Edition  1371
U
• Findings typical of chronic kidney disease 
when both kidneys are parasitized.
• Colorless, slightly pitted ova with bipolar 
plugs in urine sediment are diagnostic.
• Consider fecal contamination of urine with 
Trichuris vulpis  or other morphologically 
similar ova if free-catch urine specimens are 
used, or if inadvertent rectal puncture and 
aspiration of feces with T. vulpis  occurs 
during cystocentesis.
• Urine contamination of feces can produce 
false fecal examination findings.
• Symptomatic infections are usually 
associated with evidence of hematuria, pyuria, 
and proteinuria. Bacterial urine cultures are 
typically sterile.
N/A
IMAGING
D. renale
• Radiography may reveal renomegaly. If IV 
urography is performed, it may be 
characterized by inability of the parasitized 
kidney to excrete the contrast agent.
• Ultrasonography may reveal the affected 
kidney to be hydronephrotic and find 
characteristic hypoechoic loops associated with 
one or more of these parasites in the renal 
pelvis. T ransverse plane sonography of the 
affected kidney may reveal a thin hyperechoic 
rim that contains multiple circular structures 
of uniform diameter. The outer layers of these 
parasites are hyperechoic; the inner portions 
are hypoechoic. If parasites are in the 
peritoneal cavity, sonography may reveal 
hyperechoic curvilinear bands in the region of 
the right caudal lobe of the liver and/or the 
cranial pole of the right kidney. Serially 
performed studies may reveal movement of the 
parasite from one location to another.
• CT and MRI scans may also be used to 
detect D. renale  in the renal pelvis of one or 
both kidneys, in the peritoneal cavity, or in 
varying positions between the lobes of the liver.
N/A
  TREATMENT
D. renale
Nephrectomy is usually the treatment of choice 
when only one kidney is affected and the 
opposite kidney is capable of sustaining 
homeostasis. Parasites that are incidental findings 
in the peritoneal cavity during celiotomy may be 
removed without further morbidity.
• Infection is usually self-limiting in cats 
and dogs.
• If infected dogs are isolated, after 10–12 
weeks ova are no longer detectable in the 
urine sediment.
• Replacing soil surfaces with sand, gravel, or 
concrete may reduce prevalence of infection 
in kennels contaminated with P . plica  and P.  
feliscati .
D. renale
N/A
• Consider anthelmintic therapy if clinical 
signs are present and persist; monitor 
therapeutic success by examining urine 
sediment for ova and observing status of 
• Multiple courses of treatment may be 
necessary to eliminate the infection.
• Fenbendazole 50 mg/kg PO q24h for 3 days.
• Ivermectin 0.2 mg/kg SC once has been 
suggested as an alternative therapy, but 
objective information on its efficacy in this 
disease is limited.
• Oral treatment with albendazole 50 mg/kg 
PO q12h for 30 days was reported to be 
effective in dogs.CONTRAINDICATIONS/POSSIBLE 
N/A
  FOLLOW-UP
D. renale
Dogs and cats should not be fed raw fish or 
fish viscera, especially in areas where D. renale  
is known to exist and should not be given 
access to lake or pond water likely to contain 
infective stages of D. renale .
Monitor treatment success by examining 
urine sediment for ova and observing status of 
clinical signs. In the absence of reinfection, 
urinary capillariasis may be self-limiting. 
Isolation of dogs and cats from earthworms 
should be sufficient to eliminate a Capillaria  
bladder infection in 90 days.
Capillaria  spp. pose no known public health 
risks.
Companion Animal Parasite Council: http://
www.capcvet.org
Brown SA, Prestwood KA. Parasites of the 
urinary tract. In: Kirk RW, ed., Current 
Veterinary Therapy IX. Philadelphia, PA: 
Saunders, 1986, pp. 1153–1155.
Osborne CA, Stevens JB, Hanlon GF , et al. 
Dioctophyma renale in the dog. J Am Vet 
Med Assoc 1969, 155:605–620.
Author  Hasan Albasan
A. Osborne.(continued)  Urinary Tract Parasites

1372  Blackwell’s Five-Minute Veterinary Consult  
UUrolithiasis, Calcium Oxalate
 BASICS
Formation of calcium oxalate (CaOx) uroliths 
within the urinary tract and associated clinical 
conditions (e.g., urinary obstruction, idio  - 
pathic hypercalcemia, chronic kidney disease).
Presence of hypercalciuria, hyperoxaluria, 
hypocitraturia, and defective crystal growth 
Hypercalciuria
In dogs, normocalcemic hypercalciuria may 
result from intestinal hyperabsorption of 
calcium (so-called absorptive hypercalciuria: 
type 1—dietary independent, type 2—die -
tary dependent, and type 3—phosphaturic 
induced hypervitaminosis D) or reduced 
renal tubular reabsorption of calcium (renal 
leak hypercalciuria). Hypercalcemic hyper  - 
calciuria results from excessive glomerular 
filtration of mobilized calcium, which 
overwhelms normal renal tubular reabsorp -
tive mechanisms (called resorptive hypercal -
ciuria, since bone resorption is associated 
with high serum calcium concentrations).
Hyperoxaluria
In humans, hyperoxaluria is associated with 
inherited abnormalities of excessive oxalate 
synthesis (primary hyperoxaluria types I, II, 
and III), excess consumption of foods 
containing high quantities of oxalate or 
oxalate precursors, pyridoxine deficiency, and 
disorders associated with fat malabsorption 
(i.e., fat complexes with intestinal calcium 
augmenting intestinal absorption of oxalate). 
Lack of oxalate-degrading bacteria in the 
intestine can increase the quantity of oxalate 
absorbed from the diet and the quantity 
excreted in urine.
Hypocitraturia
Urine citrate inhibits CaOx urolith forma-
tion. By complexing with calcium ions to 
form the relatively soluble salt calcium citrate, 
citrate reduces the quantity of calcium 
available to bind with oxalate. In normal 
dogs, acidosis is associated with low urinary 
citrate excretion, whereas alkalosis promotes 
urinary citrate excretion.
Defective Crystal Growth Inhibitors
Large-molecular-weight proteins in urine, 
such as Tamm-Horsfall mucoprotein, 
nephrocalcin, and osteopontin, have a 
profound ability to enhance solubility of 
CaOx. Urine from dogs with CaOx uroliths 
revealed that nephrocalcin had fewer 
carboxyglutamic acid residues than nephro  - 
calcin isolated from normal dog urine.Feeding Diets Promoting Urine 
Acidification
Diets designed to promote aciduria are a 
common risk factor in cats and dogs. In 
several species, acidic urine is associated with 
hypercalciuria (bone mobilization of calcium, 
increased glomerular filtration of calcium, 
and decreased renal tubular reabsorption of 
calcium) and hypocitraturia (increased renal 
tubular reabsorption).
Renal/urologic
In dogs, CaOx accounts for approximately 
40% of the uroliths removed from the lower 
urinary tract and 45% of those removed from 
the upper urinary tract. In cats, CaOx 
accounts for approximately 40% of the 
uroliths removed from the lower urinary tract 
and 90% of those retrieved from the upper 
Species
• Dogs—reported in many breeds. Six breeds 
represent 60% of cases: miniature schnauzer, 
Lhasa apso, Yorkshire terrier, bichon frisé, 
shih tzu, and miniature poodle.
• Cats—Himalayan, Scottish fold, Persian, 
ragdoll, and Burmese are at greater risk.
• Dogs—8.5 ± 3 years; 60%, 6–11 years.
• Cats—97% >2 years; 53%, 7–15 years.
Mostly male dogs (73%) and male cats 
(55%).
SIGNS
• Asymptomatic in some animals.
• Depend on location, size, and number of 
uroliths.
• Animals with nephroliths are typically 
asymptomatic but may have persistent 
hematuria.
• Ureteral obstruction associated with 
contralateral microrenale, ipsilateral 
hydronephrosis, and acute onset of uremia 
occurs frequently in cats with chronic kidney 
disease.
• Typical signs of urocystoliths or urethroliths 
include pollakiuria, dysuria, and hematuria. 
Some may present for urethral obstruction.
• Nephroureteroliths common (45%) in cats 
with chronic kidney disease.
• Detection of urocystoliths are by abdominal 
or urethral palpation; failure to palpate uroliths 
does not exclude them from consideration.• Large urinary bladder with complete 
urethral obstruction (more common in cats).
• Urocystoliths with irregular contours rarely 
cause complete urethral obstruction.
CAUSES
• Oral calcium supplements given independ-
ent of meals.
• Feeding acidifying foods that promote 
formation of aciduria (pH <6.6 in dogs and 
<6.25 in cats) was associated with CaOx 
urolithiasis. In normal cats, alkaline urine was 
associated with the lowest saturation for CaOx.
• Aciduria was a risk factor for first-time 
CaOx urolith formation in dogs.
• In healthy cats, urinary undersaturation for 
CaOx was achieved by inducing alkaluria via 
dietary formulation with potassium citrate.
• Excessive dietary protein, sodium (>1.2% 
DMB or 350 mg/100 kcal) and vitamin D 
promote hypercalciuria.
• Additional dietary oxalate (e.g., chocolate 
and peanuts) and ascorbic acid promote 
hyperoxaluria.
• Glucocorticoids and furosemide promote 
hypercalciuria.
• Vitamin B6-deficient diets (e.g., home-
made) promote hyperoxaluria.
• Consumption of dry diets has a higher risk 
for CaOx urolith formation than consump-
tion of high-moisture canned diets.
 DIAGNOSIS
• Urethral obstruction, urinary tract 
infection, urinary tract neoplasia, and idio  - 
pathic feline lower urinary tract disease.
• Other common radiodense uroliths are 
magnesium ammonium phosphate, calcium 
phosphate, and silica.
• Hematological and serum profile results are 
• Urinalysis may reveal CaOx crystals, but 
absence of crystalluria does not exclude 
uroliths as a possibility.
• Hypercalcemia (rare in dogs, more 
common in cats) should be further evaluated 
to determine its cause and contribution to 
urolith formation.
Quantitative mineral analysis of uroliths.
IMAGING
• CaOx uroliths ≥2 mm in diameter are 
radio-opaque and easily detected by survey 
radiography. IV urography, contrast pyelogra-
phy, or ultrasonography may be needed to 
verify ureteral obstruction.

Canine and Feline, Seventh Edition  1373
U(continued)  Urolithiasis, Calcium Oxalate
• Urinary tract mineralization may resemble 
uroliths.
 TREATMENT
• CaOx uroliths are not amenable to medical 
• Small stones that can pass through the 
urethra (<3 mm in most dogs >5 kg) should 
be removed by voiding urohydropropulsion 
or basket retrieval. Percutaneous cystoli -
thotomy or routine cystotomy can be used 
to remove stones in smaller dogs and male 
cats.
• Consider laser lithotripsy, percutaneous 
cystolithotomy, or routine cystotomy to 
remove larger stones from the urinary 
bladder.
• Urethral surgery is discouraged. Retrograde 
urohydropropulsion is an effective procedure 
to flush urethral stones back into the urinary 
bladder prior to their removal from the 
• Persistently obstructed ureters require 
urgent intervention to minimize progressive 
kidney damage. See Ureterolithiasis.
• Removal of unobstructing nephroliths is 
usually unnecessary.
ACTIVITY
Reduce during the period of tissue repair after 
surgery.
DIET
• Studies support feeding high moisture 
foods that promote formation of less acidic 
urine (pH >6.3–6.6) to minimize formation 
of CaOx.
• Hypercalcemia in cats without evidence of 
hyperparathyroidism or malignancy is 
sometimes minimized by feeding Hill’s 
Prescription Diet Feline w/d.
• Urolith removal does not alter the factors 
responsible for urolith formation; eliminating 
or minimizing risk factors is necessary to 
minimize recurrence.
• 50% of dogs reform uroliths within 2–3 
years; 1/3 of cats reform uroliths in 2 years.
• Patients with hypercalcemia typically 
reform uroliths at a faster rate.
• Consider surgical removal of lower tract 
uroliths that cannot be removed by minimally 
invasive procedures (voiding urohydropropul-
sion, basket retrieval, intracorporeal laser 
lithotripsy, percutaneous cystolithotomy).
• Avoid performing disfiguring urethrosto-
mies and urethrotomies by using retrograde 
urohydropropulsion to flush urethroliths into 
the bladder or using lithotripsy to fragment 
urethroliths.• Shock wave lithotripsy is an alternative to 
surgery for removal of nephroliths and 
ureteroliths in dogs.
• To minimize urolith reformation over 
suture nidus, minimize surgical procedures to 
remove uroliths and use absorbable suture 
and patterns that minimize suture exposure in 
the lumen of the urinary tract.
• Only surgeons trained in ureteral surgery 
should attempt ureterolithotomy. Ureteral 
stents in dogs and subcutaneous ureteral access 
devices or stents in cats should be considered.
• Consider parathyroidectomy for patients 
with primary hyperparathyroidism.
• No available drugs effectively dissolve 
CaOx uroliths in the urinary tract. In vitro  
dissolution is seen with alkaline solutions  
(pH ≥8) of 2% or greater EDTA.
• Potassium citrate used to promote alkaluria 
should not contain cranberry supplements.
Steroids and furosemide promote calciuria.
 FOLLOW-UP
• Postsurgical radiographs are essential to 
verify complete urolith removal.
• To prevent the need for repeated surgery, 
evaluate abdominal radiography every 9–12 
months to detect urolith recurrence early. 
Small uroliths are easily removed by voiding 
urohydropropulsion or stone basket retrieval.
• Even with appropriate therapy, CaOx 
urolith recurrence is common (up to 50% in 
dogs and 33% in cats in 2–3 years). Regular 
monitoring and compliance check-ins are 
essential to adjust therapy to extend the 
interval between recurrences.
• Only recommend high-moisture foods 
(e.g., can, loaf, gravies). Feeding dry foods, 
combining dry and wet foods, or adding 
water to dry food is not effective in maintain-
ing low urinary concentrations (specific 
gravity <1.020 in dogs and <1.030 in cats) of 
calculogenic minerals.
• Feeding high-sodium foods 
(≥300 mg/100 kcal) should not be recom-
mended as a substitute for feeding high-  
moisture foods. Their efficacy to promote low 
urine specific gravity appears to be short-lived 
(3–6 months) and their use is contraindicated 
in kidney or heart disease.
• Avoid feeding diets that promote urine 
acidification. A linear increase in urine pH was associated with a linear decrease in urine 
CaOx saturation in normal cats.
• Commercially manufactured diets have 
been designed to prevent CaOx recurrence, 
but they may not be ideal for all patients.
• Hill’s Prescription Diet c/d multicare has 
been shown to decrease calcium and oxalate 
excretion in dogs with CaOx urolithiasis. This 
food has lower levels of sodium and protein.
• Hill’s Prescription Diet i/d Kiw Fat and has 
been recommended for dogs with CaOx 
urolithiasis and fat/lipid intolerance or fat/
lipid responsive diseases (e.g., dogs with a 
history of pancreatitis). Because this diet 
promotes formation of acidic urine, adminis-
ter potassium citrate to promote a more 
favorable urine pH >6.5.
• Royal Canin SO has been shown to 
decrease CaOx relative supersaturation in 
urine of urolith-forming dogs collected by 
owners. Because this diet promotes acidic 
urine, concomitant administration of 
potassium citrate is necessary to achieve a 
more favorable urine pH (>6.5). Because of 
its high sodium, this food may be inapprop -
riate for small breeds at risk for degenerative 
mitral valve disease.
• Avoid supplements with vitamins C and D.
• Reevaluate patients 2–4 weeks after initiation 
of diet therapy to verify appropriate reduction 
in specific gravity (<1.020 for dogs and <1.030 
for cats), appropriate urine pH (≥6.5), and 
amelioration of crystalluria. Do not use 
inappropriately collected or stored urine 
samples (e.g., urine collected by owners, 
refrigerated, or contaminated with debris) to 
monitor therapeutic efficacy. To promote 
dilute urine, feed canned or gravy formulations 
of food or add additional water to all types of 
food. If urine is acidic, consider administration 
of potassium citrate 75 mg/kg PO q12h; adjust 
dosage to achieve a pH between 6.5 and 7.5. 
Potassium citrate medications formulated with 
cranberry are not recommended because 
cranberry is a source of vitamin C; vitamin C 
supplementation should be discouraged 
because of its ability to increase urine oxalate.
• Vitamin B6 2–4 mg/kg PO q24–48h may 
help minimize oxalate excretion, especially 
for animals fed homemade or pyridoxine-
deficient diets.
• If dietary changes are inadequate at slowing 
the rate of recurrence, consider hydrochloro-
thiazide diuretics (dog, 2 mg/kg and cat, 
1 mg/kg q12–24h).
• If the patient is hypercalcemic, correct 
• Oxalobacter formigenes  is an intestinal 
bacterium that ingests oxalate as its sole 
nutrient. By metabolizing dietary oxalate in 
the intestine, less oxalic acid is available for 
absorption and less is excreted in urine. To 
preserve healthy populations of intestinal 
Oxalobacter , avoid indiscriminant or 
prolonged use of antimicrobics.

1374  Blackwell’s Five-Minute Veterinary Consult  
UUrolithiasis, Calcium Oxalate  (continued) 
• Urocystoliths can pass into and obstruct the 
urethra.
• Dogs that do not consume their daily 
requirement of some urolith prevention foods 
may develop various degrees of protein calorie 
• Diet-associated hyperlipidemia develops in 
some patients consuming foods with higher 
fat content. Miniature schnauzers with 
hereditary hyperlipidemia are predisposed to 
pancreatitis when consuming some 
prevention foods.
• When treating multiple conditions (obesity, 
diarrhea, etc.) consider diets that are indexed 
to also prevent CaOx.
• Approximately 50% of dogs and 33% of 
cats reform uroliths in 2–3 years. T reatment 
to minimize recurrence is helpful.
• Patients with persistent hypercalcemia 
typically reform uroliths at a faster rate.
Conditions predisposing to hypercalciuria: 
hyperadrenocorticism, acidemia, hypervitami-nosis D, and hyperparathyroidism; or 
hyperoxaluria: vitamin B6 deficiency, 
hereditary hyperoxaluria, and ingestion of 
chocolate and peanuts.
Rare in young (<1 year old) animals.
Diets used to prevent CaOx uroliths are not 
SYNONYMS
Oxalate urolithiasis.
SEE ALSO
Crystalluria.
• AAFCO = Association of American Feed 
Control Officials.
• CaOx = calcium oxalate.
Appel S, Lefebvre SL, Houston DM, et al. 
Evaluation of risk factors associated with 
suture-nidus cystoliths in dogs and cats. J 
Am Vet Med Assoc 2008, 233:1889–1895.
Kyles AE, Hardie EM, Wooden BG, et al. 
Management and outcome of cats with 
ureteral obstruction: 153 cases (1984–
2002). J Am Vet Med Assoc 2005, 
226:937–944.Lulich JP , Adams LG, Grant D, et al. 
Changing paradigms in the treatment of 
uroliths by lithotripsy. Vet Clin North Am 
Small Anim Pract 2009, 39:143–160.
Lulich JP , Berent AC, Adams LG, et al. 
ACVIM Small Animal Consensus recom-
mendations on the treatment and preven-
tion of uroliths in dogs and cats. J Vet 
Intern Med 2016, 30:1564–1574.
Lulich JP , Osborne CA. Upper tract urolith: 
questions, answers, questions. In: August 
JR, ed., Consultations in Feline Internal 
Medicine, Volume 5. St. Louis, MO: 
Elsevier Saunders, 2006, pp. 399–406.
Okafor CC, Lefebvre SL, Pearl DL, et al. Risk 
factors associated with calcium oxalate 
urolithiasis in dogs evaluated at general care 
veterinary hospitals in the United States. 
Prevent Vet Med 2014, 115:217–228.

Canine and Feline, Seventh Edition  1375
UUrolithiasis, Calcium Phosphate
 BASICS
OVERVIEW
• Calcium phosphate (CP) uroliths within the 
urinary tract and associated clinical conditions. 
• Forms of CP identified in dogs and cats 
include: calcium phosphate apatite (CAP), 
calcium phosphate carbonate (CPC), calcium 
hydrogen phosphate dihydrate (brushite), and 
uncommon minerals—  tricalcium phosphate 
(whitlockite) and octacalcium phosphate. • CP 
uroliths represent a small fraction (dogs <1.0%, 
cats <0.5%) of all uroliths submitted to the 
Minnesota Urolith Center (MUC) from 1981 
to 2018 (Table 1). • More CP uroliths are 
found in the upper tract (kidney and ureter) 
(2.5% cats, 3.5% dogs), than in the lower tract 
(bladder and urethra). • CP uroliths (excluding 
brushite) do not have a characteristic shape. 
Brushite uroliths are typically round and 
smooth. • CP uroliths are usually cream or tan 
in color. Blood clots mineralized with CP are 
typically black.
• Rarely detected in animals <1 years old.
• CPC uroliths occur primarily in female 
dogs (72%).
SIGNS
uroliths. • Pollakiuria, dysuria, hematuria, 
and urethral obstruction.  •  Nephroureteroliths—  
typically asymptomatic but may have 
persistent hematuria or signs referable to 
concomitant renal failure (primarily cats).
• CPC—commonly a minor component of 
struvite and calcium oxalate uroliths.
• Pure CP uroliths—usually associated with 
metabolic disorders, e.g., primary hyperpar-
athyroidism, renal tubular acidosis, and 
excessive dietary calcium and phosphorus.
• Urinary tract infections—increased calcium 
excretion in combination with urinary tract 
infection with urease producing bacteria may 
be risk factors favoring CPC. • Nephroliths, 
urocystoliths, and urethroliths composed of 
blood clots mineralized with CP suggest 
dystrophic mineralization of tissue, in 
contrast to metastatic mineralization 
reflecting abnormal calcium and phosphorus 
metabolism. • Other risk factors—see 
Urolithiasis, Calcium Oxalate. DIAGNOSIS
• Other common causes of hematuria, dysuria, 
and pollakiuria, with or without urethral 
obstruction, include urinary tract infection and 
urinary tract neoplasia. • Other radiodense 
uroliths—magnesium ammonium phosphate, 
calcium oxalate, and silica. • Metastatic or 
dystrophic mineralization of urinary tract 
parenchyma may resemble uroliths.
• Usually unremarkable. • Hypercalcemia or 
azotemia rarely detected; postrenal azotemia in 
some animals with complete urinary outflow 
obstruction. • Urinary sediment analysis—
amorphous crystals in some patients; brushite 
(calcium hydrogen phosphate dihydrate) forms 
are elongated, rectangular, lath-shaped crystals.
• Quantitative analysis of retrieved uroliths is 
necessary to confirm their mineral composi-
tion. • Serum concentrations of parathyroid 
hormone, parathyroid hormone–related 
peptide, and hydroxycholecalciferol may help 
establish underlying causes.
IMAGING
• CP uroliths are radiodense (as dense as bone) 
and are often detected by survey radiography.  
• CP uroliths may be detected by ultrasonography.
CP uroliths in the urethra and bladder may 
be detected by cystoscopy.
 TREATMENT
• Medical dissolution of CP uroliths remains a 
goal for the future. • Consider surgical removal of 
lower tract uroliths that cannot be removed by 
minimally invasive procedures (e.g., voiding 
urohydropropulsion, basket retrieval, intracorpor -
eal lithotripsy, laparoscopic cystotomy). • Avoid 
performing disfiguring urethrostomies by using 
basket retrieval to remove urethroliths, retrograde 
urohydropropulsion to flush urethroliths into the 
bladder or using lithotripsy to fragment 
urethroliths. • Shock wave lithotripsy is an 
alternative to surgery for removal of nephroliths, 
ureteroliths, and urocystoliths in dogs.
• Correction of hyperparathyroidism or other 
causes of hypercalcemia should minimize 
further urolith formation. MEDICATIONS
No effective medications available for 
dissolving CP uroliths.
Vitamin D supplements, other mineral 
supplements, glucocorticoids.
 FOLLOW-UP
• Radiography after surgery to verify complete 
urolith removal is a standard of practice.  
• Abdominal radiography or ultrasonography every 
3–5 months to enhance early detection of urolith 
recurrence and prevention of the need for repeated 
surgery. • Small uroliths are easily removed by 
voiding urohydropropulsion or catheter retrieval.
• A high-moisture (canned) diet formulated 
to prevent formation of calcium oxalate 
uroliths may help prevent recurrence. • Foods 
for older dogs that are lower in protein, 
phosphorus, and calcium, and which do not 
promote acidic urine are usually associated 
with decreased calcium and phosphorus 
excretion. Hill’s Prescription Diet canned g/d 
is one example. • Because of the high 
moisture content of canned foods and their 
tendency to promote dilute urine, canned 
diets are more effective than dry diets in 
preventing recurrence. • Avoid excessive 
acidification or alkalinization of urine.
SYNONYMS
Apatite uroliths.
• CAP = calcium phosphate apatite.
• CP = calcium phosphate.
• CPC = calcium phosphate carbonate.
• MUC = Minnesota Urolith Center.
Authors  Hasan Albasan and Jody P . Lulich
 Calcium phosphate uroliths submitted to the Minnesota Urolith Center (MUC) in 2013.
Dog (n = 70,481) Cat (n = 17,245)
Calcium phosphate carbonate form (CPC) 0.58% 0.09%
Calcium phosphate apatite form (CAP) 0.10% 0.17%
Calcium hydrogen phosphate dihydrate (Brushite) 0.23% 0.03%Table 1

1376  Blackwell’s Five-Minute Veterinary Consult  
UUrolithiasis, Cystine
  BASICS
OVERVIEW
• Formation of uroliths composed of cystine.
• Cystinuria—an inborn error of metabolism 
caused by defective tubular reabsorption of 
cystine, ornithine, lysine, and arginine 
(COLA) leading to cystine urolith formation.
• Cystine is freely filtered by glomeruli; 
however, most is actively reabsorbed in the 
renal proximal tubules.
• Impaired intestinal absorption of these 
amino acids has not been associated with any 
nutritional deficiency states in dogs, 
presumably because these are non-essential 
amino acids. However, cystine may be 
semi-essential amino acid and as a precursor 
of taurine, excessive cystine loss may affect 
taurine availability.
• Unless protein intake is severely restricted, 
cystinuric dogs have no detectable 
abnormalities associated with amino acid loss. 
Excessive loss of arginine in urine predisposes 
cats to hyperammonemic encephalopathy. 
Some cystinuric dogs may have carnitinuria.
• Cystinuric dogs have been classified into 
three different types: type 1 autosomal 
recessive SLC3A1  mutations found in 
Newfoundlands, Landseer, and Labrador 
retrievers; type 2 autosomal dominant 
SLC3A1  and SLC7A9  identified in Australian 
cattle dogs and European miniature 
pinschers, and type 3, which has sex-limited 
inheritance (androgen dependence) and has 
been identified in mastiffs, English and 
French bulldogs, Scottish deerhounds, and 
Irish terrriers.
• Not all cystinuric dogs and cats form 
uroliths; cystinuria is a predisposing rather 
than a primary cause of cystine urolithiasis. 
Cystine is relatively insoluble in acid urine 
and is more soluble in alkaline urine.
• This disease is genetically heterogeneous 
(SLC3A1  and SLC7A9 ) in cats as it is in dogs 
• Dogs—primarily adult (mean age 5 years; 
range 3 months–14 years) intact males, but 
may also affect females. It occurs in excess of 
100 breeds, including dachshunds, English 
bulldogs, Newfoundlands, Labrador 
retrievers, Chihuahuas, pit bulls, and French 
bulldogs. May be detected in male and female 
Newfoundland and Labradors <1 year of age.
• Cats—primarily adult (mean age at 
diagnosis, 3.5 years; range, 4 months–12 
years) males and females; most common in 
the domestic shorthair and Siamese breeds.
SIGNS
uroliths; affected animals may be asymptomatic.• Urocystoliths—include pollakiuria, dysuria, 
and hematuria.
• Urethroliths—include urethral obstruction, 
pollakiuria, dysuria, and sometimes voiding 
of small smooth uroliths. Complete outflow 
obstruction may result in postrenal azotemia 
that may progress to uremia.
• Nephroliths—typically asymptomatic; may 
be associated with manifestations of hydro  - 
nephrosis and renal insufficiency.
• Inherited defects in renal tubular 
transporters of cystine.
• In young and middle-aged dogs with 
previous history of cystine urolithiasis—
recurrence within 6–12 months 
following surgery unless prophylactic 
therapy is given.
• Urolith formation—enhanced by acidic, 
concentrated urine, incomplete and 
infrequent micturition.
  DIAGNOSIS
• Uroliths mimic other causes of pollakiuria, 
dysuria, hematuria, and/or outflow 
• Differentiate from other types of uroliths by 
urinalysis, radiography, and quantitative 
analysis of voided or retrieved uroliths.
• Urate uroliths and sterile struvite uroliths 
are of similar radiodensity.
• Cystine crystals are six-sided; insoluble in 
acetic acid.
• Positive urine cyanide-nitroprusside test.
• Urinary amino acid profiles—reveal 
abnormal quantities of cystine and, in some 
dogs and cats, ornithine, lysine, arginine, and 
other amino acids.
• Quantitative mineral analysis of uroliths.
• DNA test.
• To diagnose androgen-dependent cystinuria 
in breed without a genetic text, calculate the 
urine cystine to creatine ratio before and 3 to 
6 months after castration. A marked and 
persistent reduction is consistent with 
resolution of cystinuria via castration.
IMAGING
• Radiography—the radiodensity of cystine 
uroliths is similar to that of sterile struvite 
and silica, less than that of calcium oxalate 
and calcium phosphate, and greater than that 
of ammonium urate.
• Ultrasonography—can detect cystine 
uroliths, but does not provide reliable information about the radiodensity, shape, or 
number present.
• Urethrocystoscopy—used to detect cystine 
urethroliths and urocystoliths.
  TREATMENT
Measures to minimize urolith formation 
include changing the diet to reduce cystine 
excretion (lower methionine protein 
consumption), diluting urine to a lower 
cystine concentration, and alkalinizing the 
urine to improve cystine solubility.
Dogs
• Medical dissolution of uroliths by a 
combination of N-(2-mercaptopropionyl)-
glycine (2-MPG) and dietary therapy; Hill’s 
Prescription Diet Canine u/d reduces urinary 
excretion of cystine, promotes formation of 
alkaline urine, and reduces urine concentration; 
it is used in conjunction with 2-MPG for 
urolith dissolution and maybe effective alone 
in preventing recurrence of cystine uroliths.
• In one study, castration reduced recurrence 
of cystine uroliths in dogs identified with type 
3, sex-limited inheritance.
• Other diets are available to prevent cystine, 
but lack published results of efficacy.
Cats
Diets designed for renal insufficiency and 
geriatric cats may be suitable to minimize 
formation. Give enough potassium citrate 
40–75 mg/kg PO q12h to maintain a urine 
pH of 7.5. Choose a moist formulation diet to 
help reduce urine concentration. Dissolution 
with 2-MPG has been studied in a small 
number of cats at an oral dose of 12–20 mg/kg 
q12h. Frequency of recurrence was minimized 
in these cats without adverse side effects.
Remove urocystoliths unable to be dissolved 
by voiding urohydropropulsion, basket 
retrieval, lithotripsy, or surgery.
Urine Alkalinizers
• For patients that have acidic urine despite 
• Data from cystinuric humans suggest that 
dietary sodium may enhance cystinuria; thus 
potassium citrate may be preferable to sodium 
bicarbonate as a urine alkalinizer. Give 
enough potassium citrate 40–75 mg/kg PO 
q12h to maintain a urine pH of 7.5.

Canine and Feline, Seventh Edition  1377
U
Thiol-Containing Drugs
• 2-MPG decreases urine concentration of 
cystine by combining with cysteine to form 
cysteine-2-MPG, which is more soluble than 
cystine.
• With status as an orphan drug, ThiolaTM is 
only available from the distributor Retrophin. 
Generic 2-MPG (Tiopronin) may be 
obtained from compounding pharmacies. In 
dogs: 2-MPG may be given at a dosage of 
15–20 mg/kg PO q12h to dissolve canine 
cystine uroliths in conjunction with dietary 
therapy. In our hospital, mean dissolution 
time was 78 days (range 11–211 days).
• 2-MPG may be given at a lower dosage 
(5–10 mg/kg PO q12h) to prevent recurrent 
canine cystine uroliths.
• In cats: 2-MPG has been studied in a small 
in these cats without adverse side effects. 
Drug-induced adverse events associated with 
2-MGP are uncommon in dogs; they include 
reversible Coombs’-positive spherocytic 
anemia, thrombocytopenia, glomerular 
proteinuria, myopathy, aggressiveness, and 
increased hepatic enzyme activity.• 2-MPG should be used with caution in 
cats, as the efficacy and safety of 2-MPG has 
not been thoroughly evaluated in normal or 
cystinuric cats.
• In mouse models, l-cystine methyl esters 
have effectively disrupted cystine crystal 
growth. Future studies hope to show that 
efficacy and safety profiles are superior to 
current thiol-binding drugs.
  FOLLOW-UP
• Minimize recurrence with dietary 
management or 2-MPG.
• Monitor urolith dissolution at 30-day 
intervals by urinalysis, survey or contrast 
radiography, or ultrasonography.
• Although cystine uroliths tend to recur, 
recurrence does not affect all cystinuric dogs 
and cats.
• In some older dogs, the rate of recurrence 
declines as a consequence of a reduction in 
the magnitude of cystinuria and urine specific 
gravity.  MISCELLANEOUS
• 2-MPG =  N-(2-mercaptopropionyl)-
glycine.
Bannasch D, Henthorn PS. Changing 
paradigms in the diagnosis of inherited defects 
associated with urolithiasis. Vet Clin North 
Am Small Anim Pract 2009, 39:111–125.
Brons AK, Henthorn PS, Raj K, et al. 
SLC3A1 and SLC7A9 mutations in 
autosomal recessive or dominant canine 
cystinuria: a new classification system. J Vet 
Intern Med 2013, 27:1400–1408.
Mizukami K, Raj K, Osborne CA, Giger U. 
Cystinuria associated with different 
SLC7A9 gene variants in the cat. PLoS 
ONE 2016, 11(7):e0159247.
acknowledges the prior contribution of Carl 
A. Osborne, Eugene E. Nwaokorie, and Lisa 
K. Ulrich.(continued)  Urolithiasis, Cystine

1378  Blackwell’s Five-Minute Veterinary Consult  
UUrolithiasis, Pseudo (Dried Blood, Ossified Material)
 BASICS
OVERVIEW
Pseudo-uroliths are concretions of noncrystal-
line material that form within the urinary 
tract. They include dried solidified blood and 
ectopic bone. Pseudo-uroliths can be located 
in upper or lower sections of the urinary tract 
(renal pelvis, ureter, bladder, and urethra).
Pseudo-uroliths are primarily a disease of cats.
• Dried solidified blood pseudo-uroliths 
comprise 1% or less of feline uroliths. They 
are 2–3 times more common in male than 
female cats. The mean age of affected cats is 9 
years old (range 1–15 years).
• Ectopic bone pseudo-uroliths are rare, with 
few cases reported.
SIGNS
• Urinary tract obstructions (ureteral or 
urethral) are common. Obstructions can 
result in uremia with anorexia, vomiting, 
weakness, and, if hyperkalemia is present, 
bradycardia. Urethral obstructions can also 
cause nonproductive stranguria and a 
palpably enlarged, firm bladder.
• Other signs include hematuria, dysuria, and 
pollakiuria.
• Dried solidified blood pseudo-uroliths are 
associated with hematuria, but mechanisms 
underlying their formation are unknown. 
Concurrent urinary tract infections are 
occasionally present.
• Ectopic bone forms due to ossification of 
the urothelium. T rauma and inflammation 
are risk factors in humans, but their role in 
veterinary species has not been determined.
 DIAGNOSIS
Consider more common lower urinary tract 
diseases, such as feline idiopathic lower 
urinary tract disease, other types of urolithi-
asis (e.g., calcium oxalate and struvite), 
urethral plugs, urinary tract infection, and 
urinary tract neoplasia.
Hematuria, proteinuria, and, if obstruction is 
present, azotemia and hyperkalemia.
• Quantitative analysis (polarized light 
microscopy and infrared spectroscopy).
• Urine culture to rule out concurrent infection.
IMAGING
• Dried solidified blood is often radiolucent. 
Bladder distension will be present in the case of urethral obstruction. Pyelography can aid 
in the diagnosis of ureteral obstruction, but 
dried solidified blood pseudo-uroliths are 
infrequently identified even with this 
modality.
• Ectopic bone is radio-opaque and can be 
visualized with plain radiography.
• Patients with dried solidified blood 
pseudo-uroliths frequently have evidence of 
ureteral obstruction on ultrasound, including 
renal pelvic dilation with or without ureteral 
dilation. The pseudo-urolith is often not 
• Ectopic bone appears hyperechoic with 
distal acoustic shadowing.
Cystoscopy can characterize the appearance 
and number of pseudo-uroliths in the lower 
often black in color. Unlike blood clots, they 
are not malleable and crack with pressure. On 
histopathology, they consist of a conglomera-
tion of red blood cells that lack distinct 
borders.
• Ectopic bone is grossly adhered to the 
urothelium but can easily be detached. Other 
mineralization, such as calcium oxalate, may 
also be present.
 TREATMENT
• Urethral obstructions are treated as 
emergencies. Retrograde urohydropropulsion 
can relieve the obstruction; decompressive 
cystocentesis prior to placement of a urinary 
catheter may more rapidly reduce intravesicu-
lar pressure. Cystotomy or basket-retrieval is 
performed to remove pseudo-uroliths from 
the bladder. Voiding urohydropropulsion can 
be considered for those measuring <3 mm in 
diameter in female cats or ≤1 mm in male 
cats.
• Ureteral obstructions should also be 
managed immediately. Subcutaneous ureteral 
bypass or ureteral stenting is recommended. 
T raditional surgery is performed when these 
procedures are not available.
Neither dried solidified blood nor ectopic 
bone pseudo-uroliths are reported to be 
susceptible to medical dissolution.
N/A. FOLLOW-UP
Routine urinalysis to identify hematuria and 
serum renal biomarkers (BUN, creatinine, 
SDMA) to assess renal function.
Increased fluid intake is recommended as a 
general mechanism to decrease concretions of 
material within the urinary tract. Preventative 
strategies should be followed for any 
concurrent diseases, such as renal disease, 
urinary tract infection, or calcium oxalate 
Obstruction can result in renal damage and, 
in severe cases, fatality. Calcium oxalate 
uroliths can form on ectopic bone within the 
Recurrence rates are unknown.
Ectopic bone pseudo-uroliths can serve as a 
nidus for calcium oxalate uroliths.
Westropp JK, Ruby AL, Bailiff NL, et al. 
Dried solidified blood calculi in the urinary 
tract of cats. J Vet Intern Med 2006, 
20:828–834.
Author  Eva Furrow

Canine and Feline, Seventh Edition  1379
UUrolithiasis, Struvite—Cats
 BASICS
Struvite uroliths and urethral plugs have 
physical and etiopathogenic differences; these 
terms should not be used as synonyms. 
Struvite uroliths are polycrystalline concre-
tions composed primarily of magnesium 
ammonium phosphate (MAP) and small 
quantities of matrix. Struvite urethral plugs 
are composed of large quantities of matrix 
mixed with crystals (especially MAP), while 
others are composed primarily of organic 
matrix, sloughed tissue, blood, and/or 
inflammatory reactants.
• See Urolithiasis, Struvite—Dogs.
• Most urethral plugs contain large quantities 
of matrix in addition to minerals, especially 
struvite. Risk factors associated with 
formation of MAP crystals contained in 
urethral plugs are similar to those associated 
with formation of struvite uroliths. 
Prevention or control of these risk factors 
should minimize the recurrence of the 
struvite component of urethral plugs.
Renal/urologic—upper and lower urinary tract.
• From 1981 to 2002, the prevalence of 
struvite uroliths has decreased and while that 
of calcium oxalate (CaOx) uroliths has 
increased. In 2015, struvite comprised 49% 
and CaOx comprised 36% of feline uroliths.
• Currently, struvite makes up ~50% of all 
types of uroliths in the lower urinary tract. Of 
these, 95% are sterile.
• Struvite has been detected in approximately 
8% of feline nephroliths.
• Struvite has remained the most common 
(~90%) mineral in matrix-crystalline urethral 
plugs.
Species
Cat (see Urolithiasis, Struvite—Dogs).
• Mean age at time of diagnosis is 7 years 
(range, <1–22 years).
• Sterile struvite uroliths do not affect immature 
cats; infection-induced struvite may occur in 
immature (<1 year) and senior cats (>10 years).
• Struvite uroliths are more common in 
female cats (55%) than in males.
• Struvite urethral plugs primarily affect 
males.
SIGNS
• Affected cats may be asymptomatic.• Depend on location, size, number, and 
cause of uroliths.
• Typical signs of urocystoliths include 
pollakiuria, dysuria, periuria, hematuria, and 
sometimes voiding of small, smooth uroliths.
• Signs of renal dysfunction (polyuria and 
polydipsia) are found in some cats with 
• Signs of outflow obstruction (e.g., dysuria, 
large painful urinary bladder, and postrenal 
azotemia) are found with struvite urethral plugs.
• A thickened, firm, contracted bladder wall 
may be appreciated.
• Palpation is insensitive and unreliable for 
detection of urocystoliths.
• Urethral plugs or urethroliths may be 
detected by examination of the distal penis.
• Outflow obstruction results in an enlarged 
urinary bladder and signs of postrenal azotemia.
CAUSES
• Sterile struvite uroliths—mineral composi-
tion, energy content, and moisture content of 
diets; urine-alkalinizing metabolites in diets; 
quantity of diet consumed; ad libitum  vs. 
meal-feeding schedules; formation of 
concentrated urine; and retention of urine.
• Infection-induced struvite urolithiasis—uri-
nary tract infection (UTI) with urease-pro-
ducing bacteria, abnormalities in local host 
defenses that allow bacterial UTIs, and the 
quantity of urea excreted in urine.
• The small diameter of the male distal 
urethra predisposes to obstruction with plugs 
and urethroliths.
 DIAGNOSIS
dysuria, periuria, hematuria, and/or outflow 
• Differentiate struvite uroliths and urethral 
plugs from other types of uroliths by 
signalment, urinalysis, urine culture, 
radiography, ultrasonography, cystoscopy, and 
quantitative analysis of uroliths or plugs.
• Complete outflow obstruction may cause 
• MAP crystals typically appear as colorless, 
orthorhombic (having three unequal axes 
intersecting at right angles), coffin-like 
prisms. They often have 3–8 sides.
• Pretreatment urine cultures (preferably 
obtained by cystocentesis) can detect primary 
infections with urease-producing microbes causing infection-induced struvite uroliths 
and differentiate them from infections 
acquired as a sequelae to urolithiasis.
• Quantitative mineral analysis should be 
performed on all uroliths and plugs.
• Bacterial culture of inner portions of 
uroliths retrieved from patients with 
urease-positive UTI may be of value.
IMAGING
• Struvite uroliths—radiodense, single or 
multiple, rough or smooth, round or faceted, 
sometimes disc-shaped; some struvite urethral 
plugs may be detected by survey radiography.
• The size and number of uroliths are not a 
reliable index of probable efficacy of 
dissolution therapy.
• Contrast urethrocystography helps identify 
the site of urethral obstruction and strictures.
• Detects location and approximate size and 
number of uroliths. Tends to overestimate 
stone size and underestimate stone number.
• Does not indicate degree of radiodensity or 
shape of uroliths.
Cystoscopy reveals location, number, size, and 
shape of urethroliths and urocystoliths.
Urethral plugs may contain red blood cells, 
white cells, transitional epithelial cells, 
bacteria, and/or viruses in addition to matrix 
and minerals.
 TREATMENT
• Retrograde urohydropropulsion to 
eliminate urethral stones; lavage to remove 
urethral plugs.
• Voiding urohydropropulsion to eliminate 
small bladder and urethral stones.
• Medical dissolution of struvite uroliths is an 
outpatient strategy.
DIET
• Medical dissolution is the standard of 
practice for elimination of struvite uroliths.
• T reatment with a dedicated struvite 
calculolytic diet (e.g., Hill’s Prescription Diet 
Feline s/d) results in dissolution within 2–4 
weeks of therapy.
• T reatment with urinary therapeutic foods 
designed for struvite dissolution and CaOx 
prevention are effective but may require 
longer treatment times.
• Infection-induced struvite urocystoliths 
may be dissolved by feeding a calculolytic diet 
and an appropriate antimicrobic.
• Continue diet therapy for 1 month 
after radiographic evidence of urolith 

1380  Blackwell’s Five-Minute Veterinary Consult  
UUrolithiasis, Struvite—Cats  (continued) 
• Struvite crystalluria may be minimized by 
feeding magnesium-restricted urine-acidifying 
diets.
• Canned foods help to reduce urine 
concentration of calculogenic metabolites and 
promote increased frequency of voiding.
• If dietary management is used, limit access 
to other foods and treats.
• Short-term (weeks to months) treatment 
with a calculolytic diet and antibiotics as 
needed is effective in dissolving infection-
induced struvite uroliths.
• Owners of cats with infection-induced 
struvite urocystoliths must comply with 
dosage schedule of antibiotics.
• Avoid feeding calculolytic diets to 
immature cats.
• Ureteroliths cannot be dissolved. For 
persistent ureteroliths associated with 
morbidity, consider subcutaneous ureteral 
bypass, ureteral stents, or traditional surgery.
• Urethroliths cannot be medically dissolved. 
Consider voiding urohydropropulsion to 
remove urethroliths or urethral plugs. 
Alternatively, move urethroliths into the 
bladder by retrograde urohydropropulsion.
• Immovable urethroliths, recurrent urethral 
plugs, or strictures of the distal urethra may 
require perineal urethrostomy.
• Consider laser lithotripsy for urocystoliths 
and/or urethroliths.
• Consider surgical correction if uroliths are 
obstructing urine outflow and/or if correctable 
abnormalities predisposing to recurrent UTI 
are identified by radiography or other means.
• Radiographs should be obtained 
immediately following surgery to verify that 
all uroliths were removed.
• Dissolution of infection-induced urocysto -
liths requires appropriate antibiotics, chosen 
on the basis of bacterial culture and 
antimicrobial susceptibility tests. Give 
antibiotics at therapeutic dosages until the 
UTI is eradicated and there is no radiographic 
evidence of uroliths.
• Buprenorphine may be used to alleviate 
discomfort (15  μg/kg via buccal transmucosal administration q8–12h). 
Tolteridine may be considered as an 
anticholinergic and antispasmodic to 
minimize hyperactivity of the bladder 
detrusor muscle and urge incontinence 
(0.05 mg/kg PO q12h).
Do not give urine acidifiers to azotemic 
patients or immature cats.
Azotemic patients are at increased risk for 
adverse drug events.
 FOLLOW-UP
Check rate of urolith dissolution monthly by 
urinalysis, urine culture, survey or contrast 
• Recurrent sterile struvite uroliths may be 
prevented by using acidifying, magnesium-
restricted diets or urine acidifiers. Do not 
administer urine acidifiers with acidifying 
diets.
• For patients whose urine has been acidified, 
carefully monitor them for CaOx crystalluria. 
Change management protocol if persistent 
CaOx crystalluria develops.
• In patients at risk for both struvite and 
CaOx crystalluria, focus on preventing 
CaOx uroliths. Struvite uroliths can be 
medically dissolved; CaOx uroliths cannot 
be dissolved.
• Infection-induced struvite urolithiasis can 
be prevented by eradicating and controlling 
UTIs. Use of magnesium-restricted, 
acidifying diets is not required if the urease- 
positive microbes can be eradicated.
• Urocystoliths may pass into and obstruct 
the urethra, especially if the patient is 
persistently dysuric. Urethral obstruction may 
be managed by retrograde 
• An indwelling transurethral catheter 
increases the risk for iatrogenic bacterial UTI 
and urethral stricture.
Mean times for dissolution of sterile 
urocystoliths ranged from 13 to 36 days. 
Mean times for dissolution of infection-induced struvite urocystoliths ranged from 21 
to 44 days. Most struvite uroliths located in 
the urinary bladder can be safely dissolved 
with a low risk of adverse effects, including 
Any disease that predisposes to bacterial UTI.
Infection-induced struvite is the most 
common urolith in immature cats. Sterile 
struvite is rare in immature cats.
SYNONYMS
Feline lower urinary tract disease.
SEE ALSO
• Crystalluria.
• MAP = magnesium ammonium phosphate.
Lulich JP , Berent AC, Adams LG, et al. 
ACVIM small animal consensus recommen-
dations on the treatment of and prevention 
of uroliths in dogs and cats. J Vet Intern 
Med 2016, 30:1564–1574. 
Lulich JP , Kruger JM, MacLeay, et al. Efficacy 
of two commercially available, low-  
magnesium, urine-acidifying dry foods for 
the dissolution of struvite uroliths in cats. 
J Am Vet Med Assoc 2013, 
243:1147–1153.
Osborne CA, Lulich JP , Kruger JM, et al. 
Feline urethral plugs: Etiology and 
pathophysiology. Vet Clin North Am Small 
Anim Pract 1996, 26:233–254.
A. Osborne, Jody P . Lulich, and Eugene E. 
Nwaokorie.

Canine and Feline, Seventh Edition  1381
U
Urolithiasis, Struvite—Dogs
  BASICS
Formation of polycrystalline concretions (i.e., 
uroliths, calculi, or stones) composed of 
magnesium ammonium phosphate hexahy-
drate (MAP , struvite) in the urinary tract.
Infection-Induced Struvite
• Urine must be supersaturated with 
MAP for struvite uroliths to form. MAP 
supersaturation of urine is often associated 
with urinary tract infections (UTIs) with 
urease-producing microbes. 
• UTIs caused by urease-producing microbes 
(Staphylococcus , Proteus , and Ureaplasma ) and 
urine containing sufficient urea favors 
formation of uroliths containing struvite, 
carbonate apatite, and calcium apatite.
• Consumption of dietary protein exceeding 
the daily requirement results in formation of 
urea from catabolism of amino acids.
• Metabolic and anatomic abnormalities may 
indirectly induce struvite uroliths by 
predisposing to UTIs.
Sterile Struvite
• In dogs, this type of struvite is uncommon.
• Dietary or metabolic factors may be involved 
in the genesis of sterile struvite uroliths in dogs.
• Microbial urease is not involved in 
formation of sterile struvite uroliths.
GENETICS
• The high incidence of struvite uroliths in some 
breeds such as miniature schnauzers suggests a 
familial tendency. Susceptible miniature 
schnauzers may inherit an abnormality of local 
host defenses of the urinary tract that increases 
their susceptibility to UTI.
• Sterile struvite uroliths were found in a 
family of English cocker spaniels.
Struvite uroliths account for approximately 
40% of stones affecting the canine lower 
urinary tract and 23% of stones affecting the 
upper urinary tract.
Species
Dog
• Miniature schnauzer, shih tzu, bichon frise, 
miniature poodle, cocker spaniel, and Lhasa apso.
• Any breed may be affected.
• Mean age, 6 years (range <1 to >19 years).• Most uroliths in immature (<12 months 
old) dogs are infection-induced struvite.
More common in females ( ~85%) than 
males ( ~15%), which may be related to the 
greater propensity for females to develop 
bacterial UTI.
SIGNS
• Some dogs are asymptomatic.
• Signs depend on location, size, and number 
of uroliths and virulence of bacteria.
pollakiuria, dysuria, and hematuria; 
sometimes small, smooth uroliths are voided.
• Typical signs of urethroliths include pollakiuria 
and dysuria; sometimes small, smooth uroliths 
are voided, and some medium size uroliths are 
associated with urethral obstruction.
• Nephroliths may be associated with 
manifestations of renal insufficiency. Obstruction 
to urine outflow with bacterial UTI may result 
in generalized pyelonephritis and septicemia.
• Uroliths may be palpated in the urinary 
bladder and urethra (by rectal exam).
• Urethral obstruction may cause 
enlargement of the urinary bladder.
• Ureteral obstruction may cause enlargement 
and pain of the associated kidney.
• Complete urine outflow obstruction 
combined with bacterial infection may cause 
ascending UTI and signs of renal failure and 
septicemia.
CAUSES
• Urinary tract disorders that predispose to 
infections with urease-producing bacteria, 
fungal pathogens, or ureaplasma in patients 
whose urine contains a large quantity of urea.
• Specific causes of sterile struvite uroliths are 
unknown.
• Exogenous or endogenous exposure to high 
concentrations of glucocorticoids predispose 
to bacteriuria.
• Abnormal retention of urine.
• Alkaline urine decreases the solubility of 
struvite.
  DIAGNOSIS
signalment, rectal exam, urinalysis, urine 
culture, radiography, and quantitative analysis 
of uroliths.CBC/BIOCHEMISTRY/URINALYSIS
• Complete outflow obstruction can cause 
postrenal azotemia and hyperphosphatemia.
orthorhombic, coffin-like prisms. They may 
have 3–6 or more sides and often have 
oblique ends.
• Quantitative bacterial culture of urine, 
preferably collected by cystocentesis.
infection-induced struvite uroliths.
• Quantitative mineral analysis of urolith.
IMAGING
• Struvite uroliths are radiodense and may be 
detected by survey radiography.
• Ultrasonography can detect uroliths, but 
provides no information about their density, 
shape, or size.
• Determine precise location, size, and 
number of uroliths; the size and number are 
not a reliable index of probable efficacy of 
  TREATMENT
• Medical dissolution with antimicrobials and 
therapeutic food is preferred treatment for 
non-obstructing struvite uroliths.
• Ureteral stenting facilitates medical 
dissolution of obstructing nephroureteroliths. 
• Appropriate antimicrobic administration is 
the cornerstone of treatment for infection-
induced struvite dissolution and prevention. 
• Voiding urohydropropulsion, laser lithotripsy, 
percutaneous cystolithotomy, and/or surgery 
require short periods of hospitalization. 
DIET
• Infection-induced and sterile struvite 
urocystoliths and nephroliths may be 
dissolved by feeding a calculolytic food (Hill’s 
Prescription Diet Canine c/d, s/d, Royal 
Canin® and others).
• Continue calculolytic diet therapy for 
1 month beyond survey radiographic 
evidence of urolith dissolution.
• Avoid use of the protein restricted diet in 
patients with protein-calorie malnutrition. 
Some calculolytic diets are designed for 
short-term (weeks to months) dissolution 
therapy, rather than long-term (months to years) 
prophylactic therapy. Monitor the patient for 
evidence of protein malnutrition. Consider 
dissolution diets meeting maintenance 
nutritional requirements in immature dogs. 
Avoid high sodium foods in dogs with cardiac 
valvular disease or heart failure.

1382  Blackwell’s Five-Minute Veterinary Consult  
U• Short-term (2–3 months) treatment with a 
calculolytic food and administration of 
antibiotics is effective in dissolving struvite 
uroliths.
• Comply with dosage schedule for antibiotic 
and diet therapy.
• Ureteroliths and urethroliths may be 
difficult to medically dissolve because they are 
minimally immersed in urine.
• Consider ureteral stenting or shock-wave 
lithotripsy for persistent ureteroliths 
associated with morbidity. Ureteral stenting 
may allow for renal decompression and allow 
time for stone dissolution.
• Consider voiding urohydropropulsion 
if urethroliths are likely to pass through 
the urethra. Alternatively, consider 
laser lithotripsy or move urethroliths into 
the bladder by retrograde 
obstructing urine outflow and minimally 
invasive procedures are ineffective or not 
available. Immovable urethroliths may require 
urethrotomy or urethrostomy.
• Dietary dissolution of infection-induced 
urocystoliths or nephroliths requires oral 
administration of appropriate antibiotics, 
chosen on the basis of quantitative bacterial 
culture and antimicrobial susceptibility tests. 
Give antibiotics until there is no radiographic 
evidence of uroliths and there is eradication 
of UTI.
• In most cases, antimicrobics need to be 
administered for the entire dissolution period. 
Shorter duration may be successful if they 
sterilize the urolith (e.g., small uroliths). 
• Diet-induced polyuria will reduce the 
concentration of antimicrobial drugs in urine; 
consider this fact when calculating 
antimicrobic dosages.
  FOLLOW-UP
Monitor rate of urolith dissolution at 4 to 6 
week intervals by urinalysis, urine culture, and imaging (ultrasonography, and/or survey 
or contrast radiography).
• Infection-induced struvite urolithiasis may 
infections by urease-producing bacteria.
prevented by use of acidifying, magnesium-
restricted diets (Hill’s Prescription Diet 
Canine c/d and others) or urine acidifiers.
• Monitor patients whose urine has been 
acidified for calcium oxalate crystalluria. 
calcium oxalate crystalluria develops.
other urolith types, focus dietary prevention 
of metabolic uroliths (e.g., calcium oxalate, 
urate, cystine)— and UTI prevention for 
struvite uroliths.
• Benefits and risks are associated with 
feeding low protein-high fat struvitolytic 
diets. Potential contraindications include 
those with (1) abnormal fluid accumulation, 
(2) chronic kidney disease, and (3) 
predispositions to pancreatitis (especially 
miniature schnauzers with hyperlipidemia).
• Urocystoliths may pass into and obstruct the 
urethra. Urethral obstruction can be managed 
by retrograde urohydropropulsion or lithotripsy.
• Dysuria may be minimized by antimicrobic 
treatment of bacterial UTIs and oral 
administration of anticholinergic drugs.
• Diet-associated polyuria will result in 
voiding increased urine volume. This may be 
associated with varying degrees of urinary 
incontinence in neutered female dogs with a 
predisposition to incontinence. Allow 
frequent opportunity to urinate to minimize 
inappropriate housesoiling.
• The mean time for dissolution of all 
infection-induced urocystoliths was 3 months 
(range 2 weeks–7 months), whereas nephroliths 
took 6 months (range 2–10 months). The 
mean dissolution time of sterile struvite 
urocystoliths was 6 weeks (range 4–12 weeks).
• When feeding Hills Prescription Diet s/d, 
compliance with dietary recommendations is 
verified by a reduced concentration of urea in 
serum (approximately 10 mg/dL) and a low 
urine specific gravity (1.004–1.014).
• If uroliths increase or fail to decrease in size 
after approximately 6–8 weeks of appropriate 
management, alternative methods should be 
considered. Difficulty in inducing complete dissolution of uroliths should prompt 
consideration that (1) the wrong mineral 
component was identified, (2) the nucleus of 
the uroliths has a different mineral 
composition than other portions of the 
urolith, and (3) the owner is not complying 
with therapeutic recommendations. With the 
addition of high sodium dissolution foods 
lacking protein reduction, the proportion of 
calcium phosphate carbonate associated with 
infection-induced struvite has increased. 
Struvite uroliths with high percentages of 
calcium phosphate carbonate appear less 
amenable to medical dissolution.
Infection-induced struvite is the most common 
form of urolith in immature dogs. The uroliths 
develop as a result of microbial UTI.
• The calculolytic foods are not designed to 
sustain pregnancy.
SYNONYMS
• Phosphate calculi.
• Infection stone.
• Urease stone.
• T riple-phosphate stone.
Osborne CA, Lulich JP , Bartges JW, et al. 
Canine and feline urolithiasis: relationship 
of etiopathogenesis to treatment and 
prevention. In: Osborne CA, Finco DR, 
eds., Canine and Feline Nephrology and 
Urology. Baltimore, MD: Williams & 
Wilkins, 1995, pp. 798–888.
A. Osborne and Eugene E. Nwaokorie.
available onlineUrolithiasis, Struvite—Dogs  (continued)

Canine and Feline, Seventh Edition  1383
UUrolithiasis, Urate
 BASICS
Uroliths composed of uric acid, sodium urate, 
or ammonium urate.
• Impaired conversion of uric acid to allantoin 
(see Figure 1) causes high concentration of uric 
acid in serum and urine. •   Patients with 
portosystemic shunts may develop ammonium 
urate uroliths because of impaired hepatic 
metabolism of uric acid and ammonia.
GENETICS
Dalmatians have a breed predisposition to 
forming urate urolithiasis.
Approximately 5–8% of uroliths retrieved 
from dogs and cats.
Species
Dalmatians, English bulldogs, Black Russian 
Terriers (due to mutation in SLC2A9 gene), and 
breeds predisposed to portosystemic shunts (e.g., 
Yorkshire terriers).
• Mean age in patients without portosystemic 
shunts is 3.5 years (range 0.5 to >10 years).
• Mean age in patients with portosystemic 
shunts is <1 year (range 0.1 to >10 years).
• More common in male dogs without 
portosystemic shunts. •  No sex predilection 
in dogs with portosystemic shunts or cats.
SIGNS
Hematuria, dysuria, pollakiuria. Possible 
• Urethral obstruction. •   Asymptomatic in 
some patients. •  Stunted growth and copper- 
colored irises (cats) in patients with port -
osystemic shunts.
CAUSES
Rule out portosystemic shunt.
• High purine intake (glandular meat).
• Persistent aciduria in a predisposed animal.
 DIAGNOSIS
Other causes of lower or upper urinary tract 
disease.CBC/BIOCHEMISTRY/URINALYSIS
• Aciduria, urate crystalluria, azotemia in 
patients with urinary outflow obstruction.
• Low BUN and microcytosis in patients 
with portosystemic shunts; reduced produc-
tion of urea by the liver may mask hypoglyce-
mia, hypoalbuminemia, and increased hepatic 
enzyme activities in patients with more severe 
hepatic dysfunction.
• Liver function tests such as postprandial 
serum bile acids have abnormal results in 
patients with portosystemic shunts.
• Genetic testing for mutation in SLC2A9 
gene, which encodes for a carrier protein 
necessary for uric acid metabolism, can be 
performed in dogs without portosystemic 
shunts who are at high risk or who have 
formed urate uroliths (performed at 
University of California Davis and Embark).
IMAGING
• Urate uroliths may be radiolucent; may need 
IV pyelogram to detect nephroliths or double 
contrast cystography to detect urocystoliths. 
Microhepatica in patients with portosystemic 
shunts. •   Ultrasonography may reveal radio  - 
lucent uroliths. Patients with a portosystemic 
shunt may also have microhepatica, bilateral 
renomegaly, and a portosystemic vascular 
anomaly identified with ultrasound.
Liver biopsy; bile acids, blood ammonia; advanced 
imaging to identify portosystemic shunt.
In patients with portosystemic shunts, liver biopsy 
may reveal hepatic atrophy and/or dysplasia.
 TREATMENT
Urethral or ureteral obstruction may require 
inpatient treatment. Urate uroliths can be 
dissolved on outpatient basis.
Fluid therapy to correct dehydration.
ACTIVITY
Usually not restricted, except after surgery.
DIET
For dissolution and prevention, a high 
moisture, low-purine, urine-alkalinizing diet.
Recurrence of uroliths is possible. A plan to 
minimize recurrence should be developed.
• Minimally invasive techniques such as 
cystoscopic stone basket removal, percutaneous 
cystolithotomy or lithotripsy are preferred over 
cystotomy, urethrotomy, and nephrotomy to 
remove uroliths. •  Portosystemic shunt ligation. MEDICATIONS
Allopurinol 15 mg/kg PO q12h, a xanthine 
oxidase inhibitor, for dissolution (see Figure 2).
Glucocorticoids and other immuno -
suppressive drugs may promote 
hyperuricosuria.
Allopurinol is contraindicated in animals with 
renal failure and is not effective in animals 
Skin eruption with use of allopurinol and 
ampicillin.
 FOLLOW-UP
See Figure 3.
• High-moisture, low-purine, urine-alkaliniz-
ing diet. • Some dogs require allopurinol 
administration (5.0–7.5 mg/kg PO q12h). 
• Low uric acid excreting Dalmatians (those 
without SLC2A9 mutation) should be at 
lower risk due to decreased urinary uric acid 
excretion.
• Urethral obstruction. •   Uroliths likely to 
recur if no preventive measures.
• Medical dissolution takes an average of 
4 weeks, if there is good compliance.
• Medical dissolution usually not successful 
with portosystemic shunt.Endogenous
PurinesDieta ry
Purines
Purine Pool
Hypo xanthine
Xanthine o xidase
Uric Acid
Uricase
Allant oinXanthine
Figure 1 .

1384  Blackwell’s Five-Minute Veterinary Consult  
U MISCELLANEOUS
Portosystemic shunt.
Low-protein/purine diet is not recommended 
for pregnant or lactating animals. Suggested Reading
Bartges JW, Osborne CA, Felice LJ. Canine 
xanthine uroliths: Risk factor management. 
In: Kirk RW, Bonagura JD, eds., Current 
Veterinary Therapy XI. Philadelphia, PA: 
Saunders, 1992, pp. 900–905.
Osborne CA, Lulich JP , Thumchai R, et al. 
Diagnosis, medical treatment, and 
prognosis of feline urolithiasis. Vet Clin North Am Small Anim Pract 1996, 
26:589–628.
Consulting Editor  J.D.Foster
available onlineUrolithiasis, Urate  (continued) 
Dysuria, pollakiur ia, hematur ia
Urethral obstr uction
•  Retrograde ur ohydropropulsion
Less than dist ended
urethral diamet er
•  Voiding ur ohydropropulsion
All ur oliths r etrieved
•  Refer to prevention algor ithm
•  Refer to prevention 
   algor ithmDissolution tr eatment:
•  Diet:  restricted pur ine and
   urine alk alinizing
•  Allopur inol 15 mg/k g PO q1 2 hCystotomy and post operativ e
doub le contrast cy stograph yAll ur oliths not r etrieved
4 weeks:
•  Urinalysis
•  Doub le contrast cy stograph y
Urocystoliths not pr esent
•  Refer to prevention algor ithmUrocystoliths pr esent
Urocystoliths r etrieved and anal yzedNo change or incr ease
in siz e and/or numberDecr ease in siz e
and/or number
•  Continue therap y
Urate
•  Incr eased allopur inol
   dose by 10–25%Urocystoliths not r etrieved
•  Cystotomy
No ur oliths
•  Refer to prevention
   algor ithmStop allopur inol, continue diet, w ait 1-2 months ,
repeat doub le contrast cy stogram, r etrieve uroliths
and anal yze.
If urat e, begin allopur inol at 25% dosage r eductionXanthine
UrolithsAll ur oliths not r etrievedNo ur ethral obstr uction
•  Urethrograph y
Urocystolith siz e and number
Urocystoliths gr eater than
distended ur ethral diamet er
Figure 2.
Algorithm for treatment of urate urocystolithiasis.
•  Diet:  restricted pur ine,
Recurr ence
•  Refer to treatment algor ithm
Recurr ence:
•  Refer to treatment algor ithmNo recurrenceNo recurrence f or 6 months:
•  Evaluate every 2-4 monthsEvery 1-2 months
•  Doub le contrast cy stograph y or
   ultrasonograph y
Figure 3.
Algorithm for prevention of urate urocystolithiasis.

Canine and Feline, Seventh Edition  1385
U
Urolithiasis, Xanthine
  BASICS
OVERVIEW
• Xanthine, a product of purine degradation, 
is converted to uric acid by xanthine oxidase. 
Naturally occurring or drug-induced 
impairment of xanthine oxidase results in 
hyperxanthinemia and xanthinuria.
• Naturally occurring xanthinuria is likely 
caused by a familial or congenital defect in 
xanthine oxidase activity. In cavalier King 
Charles spaniels, an autosomal recessive mode 
of inheritance has been found.
• Acquired xanthinuria is a complication of 
allopurinol therapy. High-purine diets 
increase the risk of xanthinuria in these 
patients.
• Xanthine is the least soluble purine excreted 
in urine.
• Dog and cat. Naturally occurring xanthinu-
ria is more common in cats.
• Naturally occurring xanthinuria and 
xanthine uroliths have occurred in young 
• Cats—adult males (66%) and females 
(33%) (mean age 3.3 years; range 2 months– 
13 years). Most common in the domestic 
shorthair and domestic longhair breeds.
SIGNS
• Dependent on stone location, size, and 
number; may be asymptomatic.
• Pollakiuria, dysuria, hematuria, and voiding 
of small, smooth, yellow uroliths. Complete 
outflow obstruction may result in azotemia.
• Nephroliths may be associated with hydro -
• Xanthinuria.
• Genetic inheritance in some breeds.
• Cats—uroliths often recur unless prophy-
lactic therapy is initiated.
• Approximately 11% of cats have reoccur-
rence of xanthine uroliths. Urolith formation 
enhanced by aciduria, highly concentrated 
urine, and incomplete and infrequent 
micturition.
• In animals given excessive allopurinol, 
xanthinuria is enhanced by failure to 
appropriately restrict dietary purine precursors.
  DIAGNOSIS
• Other causes of pollakiuria, dysuria, 
hematuria, or outflow obstruction.
• Differentiate from other urolith types by 
urinalysis, radiography, and quantitative stone 
analysis.CBC/BIOCHEMISTRY/URINALYSIS
Xanthine crystals cannot be distinguished 
from urate by light microscopy; both are 
usually yellow-brown and may form varying 
sized spherules.
• Infrared spectroscopy, X-ray diffraction, or 
other quantitative techniques are required to 
differentiate xanthine from ammonium urate, 
sodium urate, and uric acid.
• High-pressure liquid chromatography of 
urine to detect xanthine, hypoxanthine, and 
other purine metabolites.
• Genetic testing for xanthinuria type 2a, 
which involves a mutation in molybdenum 
cofactor sulfurase (performed at University 
of Minnesota).
IMAGING
• Radiography—similar density to soft tissue; 
stones cannot be reliably detected.
• Ultrasonography, double contrast cysto -
graphy, and IV urography aid in detecting 
uroliths and their location.
• May be detected by urethrocystoscopy.
• Uroliths may be retrieved by aspiration via 
a transurethral catheter or voiding 
 TREATMENT
• Medical dissolution protocols for xanthine 
uroliths have not been developed.
• Remove small urocystoliths by voiding 
• Minimally invasive surgery can remove larger 
active uroliths from the lower urinary tract.
• Minimize further growth of existing 
uroliths by reducing dietary risk factors. 
Discontinue or reduce allopurinol dosages.
• Consider canned renal-failure diets to 
increase urine volume, minimize purine 
precursors, and prevent aciduria in cats.
• Consider perineal urethrostomy for 
recurrent urethral obstruction in male cats.
• Consider in aciduric patients despite dietary 
therapy.
• Potassium citrate or sodium bicarbonate—
target urine pH of 7.0–7.5.
Allopurinol
• Adjust dosage of allopurinol in context of 
urine concentration of uric acid, and quantity 
of dietary purines (see Urolithiasis, Urate).
• Allopurinol-induced uroliths may dissolve 
by discontinuing allopurinol therapy and 
feeding a low-purine diet.CONTRAINDICATIONS/POSSIBLE 
Do not use allopurinol to treat naturally 
occurring xanthine uroliths.
  FOLLOW-UP
• Monitor dissolution every 30 days by 
urinalysis, contrast radiography, or ultrasono  - 
graphy.
• Recurrence does not occur in all patients.
• Urate urolithiasis.
SEE ALSO
xanthine uroliths: risk factor management. 
Kucera J, Bulkova T, Rychlat R, Jahn P . 
Bilateral xanthine nephrolithiasis in a dog. 
J Small Anim Pract 1997, 38(7):302–305.
Osborne CA, Lulich JP , Lekcharoensuk C, 
et al. Feline xanthine urolithiasis: a newly 
recognized cause of feline lower urinary 
tract disease. In: Proceedings 21st Annual 
ACVIM Forum, Charlotte, North Carolina, 
2003, pp. 781–782.
Tsuchida S, Kagi A, Koyama H. Xanthine 
urolithiasis in a cat: a case report and 
evaluation of a candidate gene for xanthine 
dehydrogenase. J Feline Med Surg 2007, 
9:505–508.

1386  Blackwell’s Five-Minute Veterinary Consult  
UUterine Inertia
 BASICS
OVERVIEW
Failure to expel fetuses of normal size, 
presentation and posture through a normal 
birth canal at the normal end of gestation.
Primary Uterine Inertia
• Multifactorial—failure to establish a 
normal, progressive myometrial contraction 
pattern.
• Seen in bitches with fewer than 3 puppies 
in the litter—failure to initiate parturition at 
term.
• Occurs with large litter sizes—over­
stretching of the uterus.
Secondary Uterine Inertia
• Occurs following initiation of parturition 
where some or all of the litter is not expelled.
• Can be secondary to dystocia or large litter.
Queens and bitches of any breed and age.
SIGNS
• Primary—failure to initiate parturition at 
the end of gestation; dam is typically 
asymptomatic except for vaginal discharge 
(uteroverdin) following placental separation.
• Secondary—uterine contractions cease 
despite normal contractions initially; may 
deliver part of litter and then stop. Some 
primiparous queens may initiate parturition, 
and then pause for as long as 48 hours prior 
to resuming birth.
• Primary—inadequate stimulation from 
fetuses to initiate cascade of events leading to 
parturition (small litters); abnormal or 
inadequate hormones or receptors; systemic 
disease; obesity; tocolytic administration; 
hypocalcemia; uterine infection; inadequate 
or unbalanced nutrition.
• Secondary—follows exhaustion of uterine 
muscle during normal parturition of large 
litters; occurs in bitches fed diet with poor 
calcium:phosphorus ratio; occurs during 
dystocia after prolonged periods of uterine 
contraction and eventual uterine fatigue; can 
occur with uterine torsion and trauma.
 DIAGNOSIS
• Primary—inaccurate predicted parturition 
date; false pregnancy; nonviable pregnancy.
• Secondary—normal parturition; parturition 
already complete.CBC/BIOCHEMISTRY/URINALYSIS
• Normocytic, normochromic anemia 
(normal in pregnancy).
• Low total calcium or low ionized calcium 
(iCa).
Serum progesterone <2 ng/mL for 48 hours 
prior to parturition in most cases.
IMAGING
• Ultrasonography findings—fetal heart rates 
sustained <160–170 bpm indicate stress and 
need for intervention; separation of the 
placenta from the uterus—need for immedi­
ate intervention to optimize fetal survival.
• Radiographic findings—evaluate for 
presence; size; and abnormalities of presenta­
tion, position, and posture of fetus(es).
Digital vaginal examination to evaluate for 
presence of fetus within caudal birth canal 
and abnormal anatomy causing narrowed 
birth canal.
 TREATMENT
• Inpatient—if live fetus(es) are present and 
fetal stress is documented, cesarean section 
advisable to optimize fetal survival; surgery is 
the only option for primary uterine inertia 
when fetal survival is desired.
• Fluid therapy as needed to support 
hydration and vascular volume.
• Medical—for secondary uterine inertia with 
nonobstructive dystocia and no evidence of 
fetal distress.
• 10% calcium gluconate 1 mL/5 kg SC 
q4–6h or 0.2 mL/kg IV slowly.
• 2.5–5% dextrose ­containing fluids if 
hypoglycemic (can also give bolus of dextrose 
0.5 g/kg, diluted to 10% or lower, IV).
• Oxytocin typically not effective as sole 
treatment—give 15–30 minutes after calcium 
administration at 0.5–4 IU/bitch SC or IM 
or 0.5–1 IU/queen SC or IM. Do not 
administer to animals with obstructive 
dystocia.
• Bradycardia with calcium treatment; 
monitor electrocardiogram and discontinue 
treatment if noted.• Contractions may resume with calcium 
treatment and rehydration alone.
• Delaying surgery while pursuing medical 
management may decrease fetal survival rate.
• Uterine rupture (rare).
 FOLLOW-UP
• Serial assessment of blood iCa 
concentration in hypocalcemic cases (see 
Eclampsia).
• Monitor dam’s temperature and character 
of vaginal discharge daily for 5–7 days 
following dystocia or cesarean section—
concern for metritis.
• Consider elective cesarean section in cases 
of very small or vary large litters.
• Breed females in good body condition and 
monitor nutrition during pregnancy.
• Utilize tocodynamometry (Veterinary 
Perinatal Specialties, Wheatridge, CO) to 
identify and manage secondary uterine 
inertia.
• Remove females with repeated primary 
uterine inertia from breeding stock.
• Fetal death if too much time elapses before 
• Primary inertia thought to be heritable in 
some breeds of dogs and cats.
• Primary uterine inertia—idiopathic cases 
may recur on subsequent pregnancies.
• Secondary uterine inertia—will not 
necessarily recur if due to fetal factors such as 
large litter size, poor nutrition, or dystocia 
due to malpresentation.
SEE ALSO
• iCa = ionized calcium.
http://whelpwise.com/ (tocodynamometry)
Pretzer SD. Medical management of canine 
and feline dystocia. Theriogenology 2008, 
70:332–336.

Canine and Feline, Seventh Edition  1387
UUterine Tumors
 BASICS
OVERVIEW
• Rare tumors arising from the uterine 
smooth muscle and epithelial tissues.
• Comprise 0.3–0.4% of tumors in dogs and 
0.2–1.5% in cats.
• Dogs—usually benign; leiomyomas, 
85%–90%; leiomyosarcoma, 10%; other 
types (e.g., carcinoma, fibroma, fibrosarcoma, 
lipoma, extramedullary plasma cell tumor, 
mast cell tumor, hemangiosarcoma) rare.
• Cats—usually malignant (adenocarcinoma); 
include leiomyoma, leiomyosarcoma, fibro  - 
sarcoma, fibroma, lipoma, and Mullerian 
tumor (adenosarcoma).
• Metastasis—may occur with malignant forms.
• No breed predilection reported.
• Middle-aged to older animals usually affected.
• Birt-Hogg-Dube syndrome in German 
shepherd dogs has been associated with 
uterine leiomyomas, renal cystadenocarcino-
mas, and nodular dermatofibrosis.
SIGNS
• Dogs—often clinically silent and discovered 
incidentally; vaginal discharge; pyometra, 
infertility; abdominal organ compression or 
secondary metastatic signs (site specific).
• Cats—vaginal discharge (may be hemor-
rhagic); abnormal estrous cycles; polyuria; 
polydipsia; vomiting; abdominal distention, 
infertility, uterine prolapse; signs related to 
metastatic disease (site specific).
• Intact sexual status (hormonal influence).
• Nulliparous bitches have an increased risk 
of uterine pathology.
• Mutated BHD  gene in German shepherd dogs.
 DIAGNOSIS
• Endometriosis.
• Other mid-caudal abdominal masses.
N/A
IMAGING
• Abdominal radiography—may detect a 
mid-caudal abdominal mass.
• Thoracic radiography—recommended; 
assess for distant pulmonary metastasis.
• Ultrasonography—may reveal uterine mass, 
masses in uterine horns may be difficult to 
definitely identify at uterine.• Abdominal CT/MRI—further delineation 
of mass, assess for metastatic disease.
• Cytologic evaluation—however, tumors 
might be poorly exfoliative, especially if 
mesenchymal in origin; improved cytologic 
yield with epithelial malignancies (carcinoma).
• Imaging unable to differentiate between 
histologic subtypes.
 TREATMENT
Ovariohysterectomy—treatment of choice.
Doxorubicin, cisplatin, carboplatin, epirubicin—  
rational choices for palliation of malignant or 
• Doxorubicin—carefully monitor patients 
with underlying cardiac disease; consider 
pretreatment and serial echocardiograms and 
ECG.
• Cisplatin—do not use in dogs with 
preexisting renal disease; do not use without 
appropriate and concurrent diuresis; do not 
use in cats (fatal).
 FOLLOW-UP
• Malignant—consider thoracic radiographs 
and abdominal ultrasonography every 3 
months.
• CBC, biochemical profile, and urinalysis (if 
using cisplatin)—perform before each chemo -
therapy treatment.
Prognosis—excellent (cure) if benign; 
guarded if malignant; poor if metastases 
present; after chemotherapy, unknown.
BHD syndrome in German shepherd dogs 
has been associated with uterine leiomyomas.
• BHD = Birt-Hogg-Dube. Suggested Reading
Saba CF , Lawrence JA. T umors of the female 
reproductive system. In: Withrow SJ, 
MacEwen EG, eds., Small Animal Clinical 
Saunders, 2013, pp. 532–537.
Schlafer, DH. Disease of the canine uterus. 
Reprod Domest Anim 2012, 47(Suppl 
6):318–322.
acknowledge the prior contribution of Renee 
Al-Sarraf.

1388  Blackwell’s Five-Minute Veterinary Consult  
UUveal Melanoma—Cats
  BASICS
OVERVIEW
• Also called feline diffuse iris melanoma.
• The most common intraocular tumor in cats.
• Usually arise from the anterior iridal surface 
with extension to the ciliary body and choroid.
• Tend to be flat and diffuse, not nodular 
(unlike intraocular melanomas in dogs).
• Initially has a benign clinical and histologic 
• Unique feature—may develop metastatic 
disease up to several years later.
• Metastatic rate may be 8.1–63%.
• Secondary glaucoma may increase the risk 
for metastasis.
• No sex or breed predisposition.
• Average age is 9.5 years, although can affect 
any adult cat.
SIGNS
• Iris color change.
• Secondary glaucoma leading to mydriasis or 
buphthalmia, resulting in blindness.
• Iris surface—thickened, irregular, usually 
pigmented, though can be nonpigmented.
• Lesions—focal to diffuse; usually flat; slowly 
progressive; may involve one or both eyes.
• Advanced disease—often see pigmented 
tumor cells in the aqueous; homogeneously 
thickened iris, black, velvety appearance.
• May note drainage angle infiltration, which 
may result in secondary glaucoma.
  DIAGNOSIS
• Freckles (nevi) on the surface of the iris that 
do not appear to change over time—may be 
benign pigmented lesions; more likely 
melanocytoma, a benign lesion.
• Heterochromia irides—congenital, 
nonprogressive alteration in iridal pigmentation.
• Diffuse iridal color change that results from 
chronic anterior uveitis. Differs from uveal 
melanoma by the history of chronic anterior 
uveitis.
• Iris atrophy—the anterior iris stroma is lost, 
increasing visualization of the heavily pigmented 
posterior iris tissue. Iris thinning is seen as full-  
thickness holes in the iris or as retroillumination 
defects in the iris when light is bounced off the 
tapetum back through the iris.
• Limbal melanomas—benign behavior; 
usually focal, superiorly located, flat to slightly raised limbal masses that do not invade the 
uveal tract unless they are very large.
Normal
IMAGING
ultrasonography for extensive lesions—help 
determine presence and extent of metastatic 
disease.
• Recommended presurgically and every 6 
months after the diagnosis if histopathologic 
diagnosis indicates extensive disease.
including tonometry and gonioscopy.
• Iridal biopsy—may be performed, not 
beneficial for staging the disease.
• Melanocytes in the iridocorneal angle and 
ciliary vessels suggest metastatis may have 
occurred, but these may not be evident until 
years later.
  TREATMENT
• Varies with age of cat, extent and speed of 
progression, doctor’s preference, and client’s level 
of concern about the potential for malignancy.
• Old cat with slow progression—consider 
only periodic examinations and serial 
photography to monitor the progress of the 
lesion(s).
• Younger cat with rapidly progressive 
disease—consider enucleation.
• Small, isolated, freckle-like lesions have 
been apparently successfully treated with laser 
(diode) photoablation, although controlled or 
long-term follow-up studies are lacking.
• Mild to moderate diffuse iridal involvement—  
most ophthalmologists prefer a conservative 
approach of periodic examinations and serial 
photography to monitor the growth progress 
of the lesion(s). Enucleation is an alternative 
if progression can be documented or the 
owner is highly concerned about the potential 
for malignancy.
• Extensive iridal involvement resulting in 
changes in pupil shape or mobility, extra-
iridal extension, invasion into the drainage 
angle, or secondary glaucoma—enucleation is 
suggested.
• Cats with iridal thickening and iridocorneal 
angle involvement, with and without glaucoma, 
however, had similar survival times when 
compared with unaffected age-matched 
control cats.
• Advanced lesions consisting of infiltrative 
iris involvement including the posterior 
epithelium and ciliary body had decreased 
survival times, presumably as a result of 
metastatic disease.  MEDICATIONS
N/A
  FOLLOW-UP
• Intraocular pressure (IOP)—quarterly 
monitoring if surgical options are declined; 
mild IOP elevation may be treated with oral 
or topical carbonic anhydrase inhibitors (e.g., 
dorzolamide or brinzolamide at 1 drop to 
affected eye q8h, or methazolamide at approx  - 
imately 6.25 mg per cat PO q12–24h); 
secondary glaucoma due to melanoma is best 
controlled by enucleation.
• Common metastasis sites—liver, lungs, 
regional lymph nodes; monitor periodically.
• One long-term study shows that patients 
with early iris melanoma have no increased 
risk of life-threatening metastasis compared to 
controls, but patients with advanced lesions 
have dramatically shortened survival times.
• Lesions—focal, multifocal to diffuse; 
usually flat; pigmentation over months to 
years (i.e., variable); may involve one or 
both eyes.
thickened iris causing abnormal pupil shape 
and change in pupil mobility.
• Prognosis—guarded, even with enucleation; 
metastasis may not become apparent for 
several years or may be diagnosed on 
necropsy.
SYNONYMS
• Feline diffuse iris melanoma.
• Iris melanoma.
Dubielzig RR. Ocular neoplasia in small 
Pract 1990, 20:837–848.
Schaffer EH, Gordon S. Feline ocular 
melanoma. Clinical and pathologico-
anatomic findings in 37 cases. Tierarztl Prax 
1993, 21(3):255–264.

Canine and Feline, Seventh Edition  1389
UUveal Melanoma—Dogs
 BASICS
OVERVIEW
• Melanomas of anterior uvea (e.g., iris and 
ciliary body) and posterior uvea (choroid).
• Most common primary intraocular 
neoplasm in dogs.
• Usually benign and unilateral; often 
destructive to the eye but also can be very 
slow-growing.
• Most often affects anterior uvea. In a 
retrospective study of 1842 enucleated eyes 
with uveal melanoma, 79.2% were benign 
and 20.8% malignant.
• Anterior uveal—4% rate of vascular 
metastasis to lungs and viscera, but rare for 
malignant uveal melanoma to metastasize.
• Choroidal—rarely metastasize.
• Anterior uveal—average age 8–10 years.
• Choroidal melanoma—average age 6.5 
years.
• Range—2 months–17 years.
SIGNS
Anterior Uveal
• Pigmented scleral or corneal mass.
• Pigmented mass visible in anterior chamber 
or posterior to pupillary margin.
• Irregular pupil.
• Uveitis.
• Hyphema.
• No vision loss—unless mass obstructs pupil 
or glaucoma has developed.
Choroidal
• Often missed because of tumor location; 
usually incidental finding.
• Posterior segment mass on funduscopy.
• Very slow-growing; rarely require 
• Rare.
• Potential transformation of flat, pigmented 
iris freckles into melanomas.
• Labrador retrievers—presumed autosomal 
 DIAGNOSIS
• Non-neoplastic uveal proliferations—iris 
freckles are not raised.
• Diffuse iris hyperpigmentation secondary 
to chronic uveitis, particularly in golden retrievers (golden retriever pigmentary uveitis) 
and boxers.
• Ocular melanosis (Cairn terriers).
• Uveal cysts—transilluminate and move 
freely within the eye, unlike melanomas.
• Granulomatous masses.
• Iris bombé.
• Ocular perforation with uveal prolapse.
• Other ocular neoplastic conditions, 
especially conjunctival melanoma, which 
could be misinterpreted as extrascleral 
extension of uveal melanoma. Conjunctival 
melanoma is usually malignant and aggressive 
in dogs.
• Outward scrolling of pupillary margin due 
to uveitis (ectropion uvea).
N/A
IMAGING
Ocular ultrasonography—may help deter-
mine extent of mass.
• Slit-lamp biomicroscopy—determine size 
and location of mass.
• T ransillumination of mass.
• Tonometry.
• Indirect ophthalmoscopy—with or without 
concomitant scleral indentation.
• Gonioscopy—evaluate drainage angle for 
tumor extension.
• Ocular ultrasonography—if cornea opaque 
and cannot visualize deeper ocular structures, 
or suspect ciliary body mass hidden by iris.
• Restricted to enucleated globe; biopsy not 
practical in most patients.
• T wo cell types usually seen—plump cells 
filled with melanin, spindle cells.
• Mitotic index—most reliable criterion for 
malignancy:
◦  <2 mitotic figures per 10 HPF: benign.
◦  4 mitotic figures per 10 HPF: clinically 
malignant tumors.
• Veterinary ocular pathologist should 
evaluate globe.
 TREATMENT
• Usually benign, may opt to monitor q3–6 
months.
• Young Labrador retrievers—aggressive 
growth, need surgery.
• Counsel client about enucleation; surgery 
often causes client emotional distress:
◦  Emphasize unilateral condition, sparing 
of fellow eye, and that one-eyed animals 
function very well.• Indications for enucleation—rapid size 
increase, eye cannot be salvaged, mass spread 
diffusely within eye, visual function signifi-
cantly impaired, extraocular invasion, 
secondary complications (e.g., glaucoma, 
pain, hemorrhage).
• Enucleation—use gentle surgical technique 
to prevent showering of tumor cells into 
circulation, avoid tension on optic chiasm 
(could blind fellow eye), exenterate entire 
orbital contents if extrascleral extension.
• Sector iridectomy for discrete small 
masses—infrequently used.
• Laser treatment of small iris tumor.
• Melanoma vaccine efficacy unknown; likely 
ineffective without enucleation. Consider 
vaccine if malignant melanoma is present, to 
try to prevent metastasis.
Reseveratrol, a potent antioxidant derived 
from grapes, inhibited uveal tumor growth of 
uveal melanoma in vitro , but grape skins may 
be toxic to dogs. Grapeseed extract is a safe 
alternative that may support ocular health of 
N/A
 FOLLOW-UP
• Postoperative thoracic and abdominal 
radiography or ultrasonography—at 6 and 12 
months if mitotic index is high or patient has 
extrascleral, vascular, or optic nerve extension.
• Evaluate enucleation site for tumor 
Cook CS, Wilkie DA. T reatment of presumed 
iris melanoma in dogs by diode laser 
photocoagulation: 23 cases. Vet 
Ophthalmol 1999, 2:217–225.
Dubielzig RR. T umors of the canine globe. 
World Small Animal Veterinary Association 
World Congress Proceedings, 2011.
Wilcock BP , Peiffer RL. Morphology and 
behavior of primary ocular melanomas in 
91 dogs. Vet Pathol 1986, 23:418–424.

1390  Blackwell’s Five-Minute Veterinary Consult  
UUveodermatologic Syndrome (VKH)
 BASICS
OVERVIEW
• Rare canine syndrome similar to Vogt–
Koyanagi–Harada (VKH) in humans.
• Chronic granulomatous inflammatory 
condition of unknown etiology.
• Affects the meninges, eyes then skin.
• Clinical signs reflect melanin as the target 
Likely an autoimmune process against antigenic 
components of melanocytes, suspected 
tyrosinase and related proteins; involves T-cells 
and macrophages for skin lesions and B-cells 
and macrophages for ocular lesions.
• Nervous (rarely).
• Akita, Samoyed, Siberian husky, Alaskan 
Malamute, old English sheepdog, and chow 
chow predisposed.
• Other breeds and mixed breeds reported.
• Suspected heritability: canine leukocyte 
antigen DLA-DQA1*00201 has been 
associated with an increased risk for uveoder-
matological syndrome.
• Mean age of onset 6 months–6 years.
SIGNS
• Ophthalmic signs almost always precede 
dermatologic signs.
• Sudden-onset uveitis (photophobia, blepharos -
pasm, conjunctival inflammation, pain).
• Secondary changes include glaucoma, 
cataracts, bullous retinal detachment, and 
progression to blindness.
• Unilateral uveitis may be seen in dogs with 
heterochromic irides.
• Concurrent or subsequent leukoderma of 
the nose, lips, and eyelids.
• Depigmented nasal planum may develop 
crusting and ulceration.
• Concurrent or subsequent striking 
leukotrichia of the muzzle and periorbital 
regions.
• Footpads, scrotum, vulva, anus, and oral 
cavity (hard palate) may also depigment.
• Neurologic symptoms (meningoencephali-
tis,) possible, but very rare.
• Exact cause is unknown.
• Most likely an inherited autoimmune disorder.
• Skin trauma or infectious agent (e.g., virus) 
are possible triggers.• Exposure to sunlight can exacerbate the 
symptoms.
 DIAGNOSIS
• Pemphigus foliaceus/erythematosus.
• Discoid/systemic lupus erythematosus.
• Mucocutaneous pyoderma (severe).
• Vitiligo.
• Neoplasia—epitheliotropic lymphoma.
• Numerous inflammatory and infectious 
dermatoses can cause depigmentation.
• Ocular—any cause of uveitis or glaucoma 
including neoplasia, trauma, infection and 
idiopathic causes.
Normal
ANA—negative .
• Skin biopsy necessary for diagnosis, 
especially when correlated with ocular disease.
• Examination by veterinary ophthalmologist 
strongly recommended.
Lichenoid to interface dermatosis consisting 
of mostly histiocytic inflammation; macrophages 
containing granular melanin pigment; 
 TREATMENT
• Aggressive and rapid initiation of immuno-
suppressive therapy required to prevent 
formation of posterior synechiae and 
secondary glaucoma, cataracts, or blindness.
• Retinal exams are the most important 
means of monitoring progress; improvement 
in dermatologic lesions may not reflect 
continued retinal pathology.
• Bilateral enucleation can improve patient 
comfort and attitude when eye condition 
worsens and medical treatment is unsuccessful.
• Management by a veterinary ophthalmolo-
gist is strongly recommended.
• Initial high doses of prednisone 1.1–2.2 mg/
kg PO q12–24h.
• Cases may improve with use of prednisone 
alone, but delaying aggressive therapy risks 
irreversible progression of disease: concurrent 
treatment options should include:◦  Azathioprine 1.5–2.5 mg/kg PO q24h in 
resistant cases; the dosage and frequency 
should be tapered to q48h for maintenance 
of remission.
◦  Doxycycline 10 mg/kg q24h with 
niacinamide (250 mg patients <10 kg; 
500 mg patients >10 kg q24h).
◦  Cyclosporine (modified) 5 mg/kg PO 
q24h; the dosage and frequency may be 
tapered for maintenance of remission.
• Topical or subconjunctival steroids and 
cycloplegics may be indicated if anterior 
uveitis is present.
 FOLLOW-UP
• Weekly retinal examinations and lab work 
(based on medications prescribed). 
Dermatologic lesions may not mirror 
improvement in retinal lesions.
• Tapering of drugs should be based on 
improvement of ocular lesions.
• Severe opportunistic infections may occur 
with long-term use of combination immuno-
suppressive agents.
• Generally good for dermatologic symptoms.
• Guarded to poor for vision unless treatment 
is quickly instituted and is effective.
• Some breeds (e.g., Akita or Siberian husky) 
may respond more poorly to treatment.
SEE ALSO
• Dermatoses, Depigmenting Disorders.
• ANA = antinuclear antibody.
• VKH = Vogt–Koyanagi–Harada syndrome.
http://www.veterinarypartner.com/Content.
plx?P=A&A=1714&S=0&EVetID=3001459
Zarfoss MK, T usler CA, Kass PH, et al. 
Clinical findings and outcomes for dogs 
with uveodermatologic syndrome. J Am Vet 
Med Assoc 2018, 252:1263–1271.
Authors  Austin Richman and W. Dunbar 
Gram
Resnick

Canine and Feline, Seventh Edition  1391
VVaginal Discharge
 BASICS
Any substance emanating through the vulvar 
labia.
• Dependent on underlying cause of vaginal 
• Discharge may originate from uterus, 
vagina, vestibule, clitoris, clitoral sinus, 
perivulvar dermis, or urinary tract.
• Renal.
• Skin.
• Urinary.
• Unknown as there are many causes.
• Considered a common reason for seeking 
veterinary care.
• Healthy bitch <6–12 months of age 
(prepubertal)—juvenile (puppy) vaginitis and 
congenital anomalies more common.
• Nonpregnant bitch that has undergone at 
least one estrous cycle—normal estrus, 
persistent estrus (cystic ovarian disease or 
granulosa cell tumor), pyometra, neoplasia
• Bitch bred in the last 30–70 days—normal 
parturition (50–70 days) or abortion (<50 
days).
• Bitch that has recently whelped—normal 
lochia or postpartum metritis more common, 
subinvolution of placental sites.
• Ovariectomized bitch—vaginal stricture or 
estrogen-responsive urinary incontinence 
more common; neoplasia.
SIGNS
• Discharge from the vulva.
• Licking, scooting, and spotting.
• Attracting male dogs.
• Parturition—with postpartum discharge.
• Recent estrus—with pyometra.
• Hemorrhagic discharge >8 weeks 
postpartum—subinvolution of placental 
sites.
• Vomiting, anorexia—may be seen with 
metritis and pyometra.
Vaginal discharge that may be serosan-
guinous, purulent, lochial, hemorrhagic, 
mucoid, or urinous.
CAUSES
Normal Physiologic Conditions
• Proestrus.
• Estrus.
• Late pregnancy.• Parturition.
• Normal lochia.
Pathologic Conditions
See specific chapters for further information.
• Cystic ovarian disease (persistent estrus).
• Brucella canis  infection.
• Metritis.
• Retained placenta or fetuses.
• Subinvolution of placental sites (hemor-
rhagic discharge postpartum ≥8 weeks).
• Neoplasia—uterus, vagina, urinary tract 
(including transmissible venereal tumor), 
ovary (granulosa cell tumor/persistent estrus).
• Estrogen-responsive urinary incontinence.
• Congenital defects of the distal genital 
tract—intersex conditions, imperfect 
embryologic fusion of the Müllerian ducts 
(vagina), joining of the genital folds 
(vestibule) and genital swellings (vulvar lips), 
• T rauma.
• Prophylactic antibiotics—may alter normal 
vaginal flora and predispose to secondary 
• Exogenous estrogen—predispose to 
pyometra in the intact bitch.
• Exogenous androgens—may cause clitoral 
• Exogenous or endogenous progesterone—
predispose to pyometra or stump pyometra.
• Obesity—excess skin folds around vulva.
 DIAGNOSIS
• Healthy intact bitch <6–12 months of 
age—juvenile vaginitis (prepubertal), normal 
estrous cycle, urogenital trauma or neoplasia, 
foreign body, coagulopathy, ectopic ureter(s), 
congenital abnormalities of the perineum or 
distal genital tract, intersex conditions, 
pyometra, split heat, foreign body, urogenital 
trauma, neoplasia, coagulopathy, cystic 
ovarian disease (follicular cysts).
• Bitch bred in the last 30–70 days—abor-
tion, pyometra, normal parturition (>57 days 
from breeding), fetal/embryonic death, split 
heat, Brucella canis  infection.
• Bitch that has recently whelped—lochia 
(normal up to 6–8 weeks postpartum), 
subinvolution of placental sites (hemorrhagic 
discharge ≥8 weeks postpartum), postpartum 
metritis, vaginal trauma, retained placenta or 
fetus.• Ovariectomized bitch—vaginal stricture, 
foreign body, neoplasia, polyps, stump 
pyometra due to exogenous or endogenous 
progesterone, exogenous estrogens (exposure 
to owner’s hormone replacement therapy), 
perivulvar dermatitis, ovarian remnant 
syndrome, estrogen-responsive urinary 
• Regenerative anemia—may be normal in 
pregnancy or during estrus.
• Urinalysis—may indicate urinary tract 
• Progesterone—determine if bitch is in 
luteal phase, which increases likelihood of 
pyometra. Progesterone, 17-hydroxyproges-
terone may be secreted in animals with 
adrenal cortex disease.
stimulation test—to diagnose adrenocortical 
disease.
• Brucella canis  serology—screen with rapid 
slide agglutination test; agar gel immuno -
diffusion test confirmatory.
• Bacterial culture of whole blood or lymph 
node aspirate for B. canis .
• PCR for B. canis available, best to use on 
abortive discharge (Kansas State Veterinary 
Diagnostic Laboratory).
IMAGING
• Detect enlarged uterus or ovary, pregnancy.
• Evidence of fetal death—presence of gas 
around fetus or misalignment and/or collapse 
of fetal skeleton.
• Determine contents of uterus; free fluid in 
the uterus is characteristic of pyometra, 
hydrometra, and mucometra.
• Pregnancy diagnosis and embryonic/fetal 
wellbeing—heartbeat may be seen as early as 
the 20th day of diestrus, heart rate <180 bpm 
indicates fetal stress.
• Masses—neoplasia, granulomas, cystic 
ovarian disease, granulosa cell tumor, or 
foreign body; saline distention of the vagina 
may help visualization.
Contrast Radiography—Vaginogram/
Urethragram/Cystogram/Excretory 
Urography
• Identify abnormal conformation or 
structure (i.e., neoplasia or foreign body) 
within the vagina.
• Rule out vestibulovaginal strictures, 
rectovaginal and urethrovaginal fistulas.
• Rule out differentials and help localize the 
problem.
• Pronounced folds (rugae) of vagina 
during estrus will cause filling defects 
(normal).

1392  Blackwell’s Five-Minute Veterinary Consult  
VVaginal Discharge  (continued) 
Vaginal Cytology
• Determine nature of discharge—inflamma-
tory, hemorrhagic, purulent.
• Evaluate epithelial cells —superficial 
(cornified) cells present under the influence 
of estrogen.
• Always performed in order to interpret 
vaginal cultures (inflammation should 
accompany infection).
Vaginal Culture and Sensitivity
• Performed prior to other diagnostic 
• Use guarded swab to sample cranial vagina.
• The vagina is not a sterile environment and 
culture of normal bitches results in growth of 
normal vaginal flora; use of vaginal cytology 
and other diagnostic tools is essential for 
interpretation of culture results.
• Most common organisms in the microbi-
ome (commensals and potential pathogens) 
are Escherichia coli , Streptococcus  spp., 
Pasteurella  spp., and Staphylococcus  spp.
• Other organisms which can be commensals 
include Mycoplasma  spp., Enterobacter  spp., 
Pseudomonas  spp., Klebsiella  spp.
• Normal microbiome consists of numerous 
opportunistic pathogens, e.g., E. coli  and 
Vaginoscopy
• Rigid cystourethroscope or ureteroscope, 
pediatric gastroscope or proctoscope, or 
flexible endoscope used to visualize vagina.
• Identify source of vaginal discharge—
uterine, vaginal, vestibular, or urethra.
• Visualize anomalies, persistent hymen, 
neoplasia, foreign body, trauma, abscess, 
and evaluate the vaginal and vestibular 
mucosa.
• Removal of foreign body or biopsy of 
vaginal mass.
Other
• Digital examination of vestibule, vaginoves-
tibular junction, and distal vagina.
• Biopsy and histopathology of mass lesions.
• Cystocentesis—urine culture and 
• Coagulation profile, platelet count.
 TREATMENT
• Based on diagnosis.
• No treatment for normal causes of vaginal 
• Ovariectomy or ovariohysterectomy (OHE) 
is treatment of choice for neoplastic conditions.• Cystic ovarian disease can be medically 
managed or ovariectomy/OHE performed.
• Removal of foreign body or surgical 
excision of mass(es).
• Surgical excision or radiation therapy 
are options for transmissible venereal 
tumor (TVT).
• Antibiotic—choice based on guarded 
cranial vaginal culture and sensitivity.
• Dopamine agonist—may be used in 
addition to PGF2 α for luteolysis via 
suppression of the luteotropic hormone 
prolactin—bromocriptine 10  μg/kg PO or 
cabergoline 5  μg/kg PO q8–24h until serum 
progesterone level <2.0 ng/mL.
• Supportive care including IV fluids as 
Certain antibiotics may be contraindicated 
during pregnancy and nursing.
Dopamine agonists—side effects include 
vomiting and nausea; can be controlled with 
antiemetics.
Aglepristone (Alizin®) 10 mg/kg SC, 2 doses 
given 24 hours apart—progesterone receptor 
antagonist that may be used alone or 
concurrently with prostaglandin therapy for 
treatment of pyometra (currently not widely 
available in the United States without special 
authorization).
 FOLLOW-UP
Subinvolution of Placental Sites
Monitor hematocrit or packed cell volume 
(PCV)—may have significant blood loss.
• Puppy vaginitis—delay elective OHE 
until after first estrous cycle in cases of 
juvenile vaginitis; may avoid chronic 
• Addition of probiotics to daily diet.
• Avoid exogenous steroids (estrogens, 
progestins, androgens).
Endotoxemia and septicemia may occur with 
pyometra or metritis. MISCELLANEOUS
Pyometra and cystic endometrial hyperplasia.
• Increased risk for pyometra after each 
estrous cycle.
• Neoplasia more common in older bitches.
• Brucella canis —fluids and fetal tissue 
during abortion are highly contaminated with 
• Immunocompromised people are at highest 
risk. Animal caretakers and pathologists are at 
risk due to high exposure.
• Neoplasia—poor prognosis for future 
• TVT—sexually transmitted disease; 
breeding should be avoided.
• Brucella canis —sexually transmitted disease 
and grave prognosis for resolution of disease 
and normal fertility; should not be used for 
breeding.
SEE ALSO
Loss)—Cats.
• Retained Placenta.
• Subinvolution of Placental Sites.
• T ransmissible Venereal T umor.
Lesions.
• OHE = ovariohysterectomy.
• TVT = transmissible venereal tumor.
Purswell BJ. Vaginal disorders. In: Ettinger 
Louis, MO: Elsevier, 2010, pp. 1929–1933.

Canine and Feline, Seventh Edition  1393
VVaginal Hyperplasia and Prolapse
 BASICS
OVERVIEW
• Protrusion of spherical or donut-shaped 
mass from vulva during proestrus or estrus, 
rarely during gestation, parturition, or after 
administration of estrogenic drugs:
◦ Type I—slight eversion of vaginal floor 
cranial to the urethral orifice but no 
protrusion through vulva.
◦ Type II—vaginal tissue prolapses through 
vulvar opening (tongue-shaped mass).
◦ Type III—donut-shaped eversion of the 
entire circumference of vaginal wall, 
including the urethral orifice, seen ventrally 
on the prolapsed tissue.
• Exaggerated response of vaginal mucosa to 
estrogen; some affected animals have follicular 
cysts.
• Despite the name, the change seen 
histopathologically is edema rather than 
hyperplasia or hypertrophy if occurring 
during proestrus or estrus.
• Severe prolapse—may occlude urethra and 
prevent normal urination.
• T rue vaginal prolapse without hyperplasia 
or edema occurs rarely pre- or postpartum 
and may include uterine body and horns.
• Young (most 18–22 months, range 6 
months–4.6 years), large-breed bitches.
• Predisposed breeds—large and brachyce-
phalic breeds (boxer, mastiff, English bulldog, 
Saint Bernard); Labrador and Chesapeake Bay 
retrievers; German shepherd dog; English 
springer spaniel; Walker hound; Airedale 
terrier; American pit bull terrier.
• Hereditary component probable—increased 
incidence in some family lines.
SIGNS
• Onset of proestrus or estrus.
• Although rare, can be seen during diestrus or 
at parturition (8–12% of cases occur at 
parturition); or after administration of estrogenic 
drugs or exposure to exogenous estrogens.
• Licking of vulvar area.
• Failure to allow copulation.
• Dysuria.
• Previous occurrence.
• Protrusion of round, tongue-shaped, or 
donut-shaped tissue mass from the vulva.
• Vaginal examination—locate lumen and 
urethral orifice; types I and II: vaginal lumen 
is dorsal to the prolapse; type III: lumen is 
central to the prolapse; urethral orifice is 
ventral to the prolapse with all three types.
• Estrogen stimulation.
• Genetic predisposition.• Dystocia.
• Increased abdominal pressure.
 DIAGNOSIS
• Vaginal polyp—differentiated by vaginal 
• Vaginal neoplasia—transmissible venereal 
tumor and leiomyoma; differentiated by 
signalment, stage of cycle, and vaginal 
• Clitoral hypertrophy; differentiated by 
physical examination.
N/A
N/A
IMAGING
N/A
Biopsy—differentiate from neoplasia.
 TREATMENT
• Outpatient; unless urethral obstruction.
• Breeding—possible by artificial insemina-
tion (discuss potential heritability).
• Prolapsed tissue—keep clean and lubricated 
with sterile water-soluble lubricant.
• Use of sugar or a 50% dextrose solution on 
edematous tissue may help to shrink 
prolapse.
• Elizabethan collar and clean indoor 
environment—minimize tissue trauma.
• Instruct client to monitor patient’s ability 
to urinate.
• If urethral obstruction present, place 
• Regression—usually begins in late estrus; 
should be resolved during early diestrus.
• Recurrence rate—66–100% at next estrous 
cycle.
• Ovariohysterectomy—prevents recurrence; 
may hasten resolution.
• Severe condition—requires surgical 
reduction or resection; identify and catheter-
ize urethra, 25% recurrence at next cycle after 
surgery.
• With dystocia, cesarean section required, 
ovariohysterectomy may be necessary.
• When occurring during pregnancy, both 
resection of prolapse and surgical reduction 
with accompanying hysteropexy have been 
successfully reported. Vaginal delivery with 
concurrent vaginal prolapse has been reported; 
close monitoring for obstructive dystocia is 
recommended. MEDICATIONS
Gonadotropin-releasing hormone (GnRH) 
2.2 μg/kg IM or human chorionic gonadotro-
pin (hCG) 1,000 IU IM—if breeding not 
planned that cycle; may hasten ovulation and 
resolution by a couple of days; not effective 
if given after ovulation (progesterone 
>8–10 ng/mL).
Avoid progestational drugs, they can induce 
pyometra.
 FOLLOW-UP
Monitor health of prolapsed tissue and the 
ability to urinate.
Ovariohysterectomy—recommended owing 
to genetic component and likelihood of 
Type III—may affect urethra and prevent 
normal urination.
PROGNOSIS
good, except with urethral involvement.
• Surgical intervention for type III—prognosis 
good.
Schaeferes-Okkens AC. Vaginal edema and 
vaginal fold prolapse in the bitch, including 
surgical management, 2001: https://www.ivis.
org/library/recent-advances-small-animal-
reproduction/vaginal-edema-and-vaginal-fold-  
prolapse-bitch
Disorders of the canine vagina, vestibule, 
and vulva. In: Johnston SD, Root Kustritz 
MV, Olson PNS, eds., Canine and Feline 
Saunders, 2001, pp. 225–242.

1394  Blackwell’s Five-Minute Veterinary Consult  
VVaginal Malformations and Acquired Lesions
  BASICS
Altered anatomic architecture due to 
congenital anomalies (imperforate hymen, 
dorsoventral septum, hymenal constriction, 
rectovaginal fistula, segmental aplasia, cysts, 
conformational defects of the vulva) and 
acquired conditions (vaginal hyperplasia, 
foreign bodies, strictures, adhesions, fistulas, 
and neoplasia).
• Normal embryologic development—paired 
paramesonephric (Müllerian) ducts fuse to 
form uterine body, cervix, and vagina; 
urogenital sinus forms the vestibule, urethra, 
and urinary bladder; hymen (composed of 
epithelial linings of paramesonephric ducts 
and urogenital sinus and an interposed layer 
of mesoderm) normally disappears by birth.
• Errors during embryonic development—
imperforate hymens; dorsoventral septae; 
hymenal constrictions (including vestibulo­
vaginal stenoses); vaginal diverticulum 
(double vagina, vaginal pouch); cysts.
Acquired
• Vaginal scarring—from trauma (mating, 
dystocia, sexual abuse) or inflammation; may 
note adhesions or strictures, which narrow 
vaginal diameter.
• Vaginal hyperplasia (dogs)—exaggerated 
response of the vaginal mucosa to estrogen; 
actually edema (vs. hyperplasia or hypertrophy).
• Neoplasia—extraluminal leiomyoma most 
common; usually old patients; no influence of 
ovarian status.
• Reproductive—interference with natural 
mating and whelping; frequently concurrent 
• Renal/urologic—urinary tract infections; 
urinary incontinence with congenital 
malformations of hymenal area.
• Skin/exocrine—perivulvar dermatitis 
secondary to vaginitis, recessed vulva 
(redundant perivulvar folds or hypoplastic 
vulva), or urinary incontinence.
GENETICS
Congenital—heritable component suspected; 
no direct evidence.
• Incidence (congenital)—unknown; 
conditions may be asymptomatic, especially if 
female never used for breeding.
• Prevalence (vaginal septa)—in one study, 
0.03%.
Species
• Congenital—none identified.
• Vaginal hyperplasia—large and 
brachycephalic breeds (boxer, mastiff, 
English bulldog, Saint Bernard); Labrador 
and Chesapeake Bay retrievers; German 
shepherd dog; English springer spaniel; 
Walker hound; Airedale terrier; American pit 
bull terrier.
• Congenital lesion—young (<2 years of age) 
intact or spayed females.
• Vaginal hyperplasia—young (<2 years of 
age) intact females.
• Acquired lesion (adhesions and strictures)—
post­pubertal females of any age.
• Neoplasia—mean age 10 years; ovarian 
status has no effect.
SIGNS
• Vulvar discharge.
• Excessive licking of vulva.
• Pollakiuria, stranguria.
• Attractive to males.
• Refuses mating.
• Evidence of vaginal discharge, perivulvar 
dermatitis, or mass.
• Recessed or hypoplastic vulva (occasional).
CAUSES
• Inflammatory.
• Hormonal.
  DIAGNOSIS
• Vaginitis—concurrent with many 
malformations; differentiated by vaginoscopy 
and vaginography.
• Urinary tract infection—differentiated by 
vaginal cytology and urinalysis (cystocentesis 
sample).
• Pyometra—differentiated by physical exam, 
abdominal ultrasonography.
• Urinalysis—possible urinary tract infection.
IMAGING
Positive-Contrast Vaginography, 
Excretory Urography
• Defines vaginal vault to cervix, urethra, 
cranial vestibule, and urinary bladder.
• Defines cervical canal and uterine lumen in 
intact patient during estrus.• Identifies strictures, septae, persistent hymens, 
masses, rectovaginal fistulas, urethrovaginal 
fistulas, vaginal rupture, and diverticulae.
• Procedure:
◦ Patients should be fasted for 24 hours; 
give enema 2 hours before procedure.
◦ Performed under sedation or general 
◦ Pass Foley catheter into vestibule, inflate 
balloon, infuse aqueous iodinated contrast 
media (1 mL/kg). Avoid overdistension and 
underdistension.
• Vestibulovaginal stenoses—ratio of maximal 
height of vagina to smallest height of vestibulo­
vaginal junction—normal >0.35, mild 
0.26–0.35, moderate 0.20–0.25, 
severe <0.20.
• Urinary incontinence—excretory urography 
to indentify ectopic ureters or intrapelvic 
bladder neck.
• Much of vagina not visible because of pelvis.
• Cranial vaginal masses may occasionally be 
imaged.
• Infusion of saline into vagina before 
examination helps differentiate luminal from 
transmural or extraluminal lesions.
Sequence of procedures is important; 
recommended order:
• Vaginal cytology—identify stage of estrous 
cycle; reveal inflammatory or neoplastic cells 
(see Breeding, Timing).
• Digital examination of vestibule and caudal 
vagina—measure diameter; identify caudal 
strictures or masses; note size and conformation 
of vulva.
• Vaginoscopy—identify strictures, 
adhesions, septa, diverticula, masses, and 
foreign bodies; may use a variety of specula; a 
long (16–20 cm), hollow, rigid ­type (e.g., 
infant proctoscope) with light source 
recommended; match speculum diameter to 
size of patient; post ­cervical fold (normal) 
obscures visualization of external os of cervix; 
rigid cystoscopes (used for transcervical 
insemination) adequate for many anomalies, 
need vaginal distension (under general 
anesthesia) with saline or air to visualize some 
anomalies or lesions.
• Imaging—see above.
• Urethrocystoscopy—identify ectopic 
ureters, other abnormalities.
• Imperforate hymen—thin fenestrated 
membrane, dorsoventral band(s), or a thick 
membrane at vestibulovaginal junction; most 
common defect; remainder of genital tract 
normal.
• Dorsoventral septum—oriented 
dorsoventrally in vagina, cranial to vestibulo­
vaginal junction; may note a double cervix

Canine and Feline, Seventh Edition  1395
V(most common variant), double vagina, or 
divided uterine fundus (rare).
• Hymenal constriction or vestibulovaginal 
stenosis—moderate to severe constriction at 
vestibulovaginal junction.
• Vaginal hypoplasia or vaginal aplasia—
vagina, cervix, uterus, vulva may be absent or 
hypoplastic.
Acquired
• Strictures and adhesions—may be identified 
anywhere in vagina or vestibule; result of 
trauma or inflammation; persistent vaginitis, 
refusal to mate, dystocia, or problems with 
micturition are common sequelae.
• Vaginal hyperplasia and prolapse.
• Vaginal neoplasia—usually extraluminal 
leiomyoma in wall of vestibule; leiomyo­
sarcomas; transmissible venereal tumors; 
lipomas; mast cell tumors; epidermoid 
carcinomas; squamous cell carcinomas; 
fibromas; fibrosarcomas; and invasive urinary 
tract carcinomas reported.
• Foreign bodies—plant material, sticks, and 
swabs.
  TREATMENT
• Usually outpatient, until nature of defect is 
ascertained.
• Inpatient—for positive contrast vagino  ­ 
graphy.
• Manual dilation (bougienage)—digitally or 
with smooth rigid object:
◦ Attempt in patients with imperforate 
hymen or mild vestibulovaginal stenosis.
◦ Perform in sedated patient gradually over 
a course of several treatments.
◦ May be performed in anesthetized 
patient at one time to maximal dilation.
◦ Typically leads to reduction, but not 
complete resolution, of clinical signs; unlikely 
to resolve moderate or severe stenoses.
As appropriate for condition.
• Resection, transection, excision—many 
minor congenital (e.g., imperforate hymen, 
small dorsoventral septa) and acquired lesions 
(small strictures, masses, or adhesions in 
caudal portion of vagina).
• Episiotomy—usually required for adequate 
surgical access.
• T­shaped vaginoplasty—described for 
vestibulovaginal stenoses; resection appears to provide best odds of resolution, although 
results are variable.
• Complete ring resection—vaginal stenosis.
• Vulvoplasty—excessive vulvar fold 
(redundant perivulvar skin fold) with or 
without increased perivulvar fat deposition; 
recessed vulva; reserved for patients with 
concurrent chronic vaginitis, vaginovulvar 
discharge, perivulvar dermatitis.
• T ransendoscopic laser ablation—one report 
for correcting a dorsoventral septum in an 
English bulldog that subsequently bred and 
delivered 4 pups vaginally.
• Ovariohysterectomy—patient has no 
breeding value; exhibits signs only during 
estrus.
• Vaginal ablation (vaginectomy cranial to 
external urethral orifice) and ovariohyster­
ectomy—patient has no breeding value; 
concurrent severe, refractory vaginitis at all 
stages of estrous cycle; severe vaginal stenosis; 
broad ­based vaginal tumors.
• Concurrent vaginitis—appropriate local 
and antibiotic therapy (see Vaginitis).
• Stenotic lesions—manual dilation in 
conjunction with corticosteroids (prednisone 
1 mg/kg PO q24h) in an attempt to prevent 
recurrence; high recurrence rates with or 
without steroids.
  FOLLOW-UP
Congenital lesions—for a familial line with a 
high number of affected individuals, 
recommend sterilization of affected individu­
als and their sire and dam.
• Dystocia, urinary tract infections, 
incontinence, and vaginitis—with vaginal 
malformations; with patients that fail to 
• Strictures and adhesions—may be post ­ 
operative complications of corrective surgical 
• Depends on severity of lesion and degree of 
inflammation after treatment.
• Prognosis after treatment for imperforate hymens, short dorsoventral bands, or caudal 
strictures or adhesions—fair to good for 
improvement of clinical signs; fair to guarded 
for complete resolution of signs and normal 
• Prognosis for hymenal constrictions, vaginal 
hypoplasia or severe cranial strictures or 
adhesions—guarded to poor for complete 
resolution of signs and normal fertility; with 
concurrent severe vaginitis, best 
recommendation is vaginal ablation.
• Urinary tract infections.
• Congenital—more likely in young bitches 
of any ovarian status.
• Vaginal hyperplasia—more likely in young 
intact bitches.
• Neoplasia of vagina or vestibule—more 
likely in old bitches of any ovarian status.
• Some patients may be bred by artificial 
insemination; possibility for a vaginal delivery 
is unlikely without correction of the anomaly.
• Warn owner that an elective cesarean 
section may be required.
SEE ALSO
• Vaginal T umors.
Seim HB. Surgeon’s Corner: Vulvoplasty. 
Clinician’s Brief: http://www.cliniciansbrief.
com/article/surgeon ­s­corner ­vulvoplasty
Lulich JP . Endoscopic vaginoscopy in the 
dog. Theriogenology 2006, 66(3):588–591.
Mathews KG. Surgery of the canine vagina 
and vulva. Vet Clin North Am Small Anim 
Pract 2001, 31(2):271–290.
K. Lyle.(continued)  Vaginal Malformations and Acquired Lesions

1396  Blackwell’s Five-Minute Veterinary Consult  
VVaginal Tumors
  BASICS
OVERVIEW
• Second most common reproductive tumor, 
comprising 1.9–3% of all tumors in dogs.
• Dogs—83% benign smooth muscle 
tumors, often pedunculated (e.g., leiomyoma, 
fibroleiomyoma, and fibroma); less common 
differentials include lipoma, transmissible 
venereal tumor, mast cell tumor, squamous 
cell carcinoma, leiomyosarcoma, hemangio­
sarcoma, osteosarcoma, or extension of 
primary urinary tract carcinomas also reported.
• Dogs—may be an incidental finding at 
necropsy.
• Cats—extremely rare; usually of smooth 
muscle origin.
• Hormonal influence—may play a role in 
the development of leiomyomas, fibromas, or 
polypoid tumors.
• Dog—mean age 10.2–11.2 years, boxers, 
nulliparous bitches more commonly affected.
• Cat—no data available.
SIGNS
Dogs
• Extraluminal—slow ­growing perineal mass; 
vulvar discharge; dysuria; pollakiuria; vulvar 
licking; dystocia.
• Intraluminal—mass protruding from the 
vulva (often at estrus if sexually intact); vulvar 
discharge; stranguria; dysuria; tenesmus.
Cats
• Firm mass in the perineal region.
• Nulliparous bitches more commonly 
affected.
  DIAGNOSIS
• Vaginal prolapse.
• Urethral neoplasia.
• Uterine prolapse.
• Clitoral hypertrophy.
• Vaginal polyp.
• Vaginal abscess/granuloma.
• Vaginal foreign body.
• Vaginal hematoma.
assess for pulmonary metastatic disease 
• Abdominal radiography—may detect 
cranial extension of a mass.
• Ultrasonography, vaginography, and urethro  ­ 
cystography—may help delineate mass.
• CT/MRI—definitive delineation of tumor, 
assess for surgical feasibility, assess for metastatic 
disease within abdominal visceral organs.
• Vaginoscopy with cytologic examination of 
an aspirate—may help determine cell type. 
Often cytology is nondiagnostic given the 
mesenchymal nature (poorly exfoliative) of 
most vaginal tumors.
• Biopsy with histopathologic examination—
often necessary for definitive diagnosis.
• Intraluminal—vestibular wall; protruding 
into the vulva; may occur singularly or as 
multiple masses.
• Extraluminal—vestibular roof; causing a 
bulging of the perineum.
  TREATMENT
• Surgical excision and concurrent ovario­
hysterectomy—treatment of choice.
• Subtotal and total vaginectomy described 
for extensive disease.
• Postoperative radiotherapy—may be of 
benefit for sarcoma and incompletely resected 
benign tumors.
• Postoperative therapy—no standard 
established.
• Doxorubicin 30 mg/m2, cisplatin 60 mg/
m2, or carboplatin 300 mg/m2—rational 
choice to palliate malignant or metastatic 
disease in dogs.
• Piroxicam 0.3 mg/kg PO SID may be 
useful especially for those dogs with primary 
urinary tumors extending into the vagina and 
• Doxorubicin—carefully monitor with 
underlying cardiac disease; consider 
ECG.
• Cisplatin—do not use in cats (fatal); do not 
use in dogs with renal disease; always use 
appropriate and concurrent diuresis.• Chemotherapy may be toxic; seek advice if 
you are unfamiliar with chemotherapeutic 
drugs.
• Piroxicam should not be used with other 
(NSAIDs) or prednisone and should be 
avoided in animals with underlying renal or 
hepatic disease. Should not be used in 
conjunction with cisplatin.
  FOLLOW-UP
ultrasonography—consider every 3 months if 
tumor is malignant.
• CBC (doxorubicin, cisplatin, carboplatin), 
biochemical profile (cisplatin, piroxicam), 
urinalysis (cisplatin, piroxicam)—perform 
before each chemotherapy treatment.
• Prognosis—good with complete excision; 
guarded if incomplete excision; poor with 
metastatic disease; poor with carcinoma or 
• Recurrence—15% (leiomyoma) without 
concurrent ovariohysterectomy.
Cats—reported concurrent cystic ovaries and 
mammary gland adenocarcinoma.
• NSAID = nonsteroidal anti ­inflammatory 
drug.
Manithaiudom K, Johnston SD. Clinical 
approach to vaginal/vestibular masses in the 
bitch. Vet Clin North Am Small Anim Pract 
1991, 21:509–521.
acknowledge the prior contribution of Renee
Al­Sarraf.

Canine and Feline, Seventh Edition  1397
VVaginitis
  BASICS
Inflammation of the vagina.
• Juvenile vaginitis—unknown, possibly due 
to imbalances of juvenile vaginal mucosal 
glandular epithelium. • Primary adult-onset 
vaginitis— Brucella canis  or canine herpesvirus. 
• Secondary adult-onset vaginitis—sequela to 
congenital anomaly, vaginal atrophy following 
ovariohysterectomy (OHE), drug therapy, 
foreign body, neoplasia, urinary tract infection, 
urinary incontinence, systemic disease.
• 0.7% of dogs in one study. • Primary 
vaginitis—very rare.
Species
Dog
• Juvenile vaginitis—less than 1 year of age, 
ranging from 8 weeks to 1 year, prepubertal 
animals. • Adult-onset vaginitis—over 1 year 
of age, ranging from 1 to 16 years of age.
SIGNS
Juvenile Vaginitis
• May have no significant history. • Vulvar 
discharge—seen most often following 
urination. • Vaginal irritation. • Crusting of 
the hair coat in the vulvar region. • Scooting. 
• Excessive vulvar licking. • Perivulvar 
pruritus. • Inability to housetrain.
Adult-Onset Vaginitis
• Vulvar discharge. • Excessive vulvar licking. 
• Pollakiuria. • Pain during urination. 
• Polyuria and polydypsia. • Pruritus. 
• Urinary incontinence. • Infertility.
• Vulvar discharge—mucoid to purulent, scant 
to copious. • Vulvar hyperemia. • Vestibular 
hyperemia. • Perivulvar dermatitis. • Digital 
examination—strictures and hymens identified 
at vagino-vestibular junction, granular 
irregularity of mucosa, especially wall opposite 
urethral papilla. • Vaginoscopy—diffuse 
hyperemia of vaginal and vestibular mucosa, 
prominent lymphoid follicles, luminal 
exudates, erythema of the urethral papilla or 
clitoral fossa; presence of foreign body, 
neoplasia, or congenital abnormalities.
CAUSES
• Prepubertal vagina. • Infantile vulva. 
• Urinary tract infection. • Urinary or fecal 
incontinence. • Foreign body. • Neoplasia—transmissible venereal tumor, leiomyoma. 
• Bacterial— Brucella canis, Escherichia coli, 
Streptococcus  spp., Staphylococcus intermedius, 
Pasteurella  spp., Chlamydia , Pseudomonas  spp., 
Mycoplasma  spp. • Viral—canine herpesvirus. 
• Congenital anomalies including vagino-
vestibular strictures, inverted vulva. • Systemic 
disease—diabetes mellitus. • Zinc toxicity. 
• Exogenous or endogenous androgens.
• Alteration of normal vaginal flora by 
antibiotics. • Clitoral hypertrophy secondary 
to exogenous or endogenous (hermaphrodites) 
androgens. • Inverted or recessed vulva. 
• Obesity. • Abnormal conformation. 
• Vaginal trauma.
  DIAGNOSIS
• Normal—hemorrhagic or serosanguinous 
discharge during proestrus, continuing into 
estrus. • Normal—slight purulent exudate in 
early diestrus; neutrophils and parabasal 
epithelial cells present. • Normal—mucus 
discharge during pregnancy. • Normal—
postpartum discharge for up to 6–8 weeks; 
odorless dark brown or hemorrhagic discharge; 
substantial amounts are normal for up to 4 
weeks. • Subinvolution of the placental 
sites—hemorrhagic discharge lasting longer 
than 8 weeks postpartum. • Cystourethritis. 
• Foreign body. • Pyometra. • Metritis. 
• Retained placenta(s). • Clitoral hypertrophy. 
• Embryonic or fetal death. • Urine or feces 
contamination secondary to congenital 
anomaly (e.g., ectopic ureter) or acquired 
condition (e.g., incontinence secondary to 
hypoestrogenism). • Perivulvar dermatitis. 
• Sexual differentiation disorder. • Vaginal 
neoplasia, trauma, hematoma, abscess. 
• Ovarian neoplasia. • Zinc toxicity.
• Usually normal. • Adult onset—pyuria, 
bacteriuria, hematuria, or systemic disease.
• B. canis  serology—rapid slide agglutination 
test, agar gel immunodiffusion test, bacterial 
culture of whole blood or lymph node 
aspirate. • Serum progesterone concentration—
determine if patient is in estrus or luteal phase 
(≥2 ng/mL).
IMAGING
• Rule out uterus as source of discharge. 
• Detection of masses; saline distention of the 
vagina may help visualization.
Urethragram/Cystogram/IV Pyelogram
structure within vagina. • Rule out vestibulovaginal strictures, rectovaginal and 
urethrovaginal fistulas.
• Use guarded swab to sample cranial vagina. 
• 74% of adult-onset cases positive for 
bacterial growth: ◦ Most common organisms 
are E. coli, Streptococcus spp., and 
Staphylococcus intermedius. ◦ Others 
include Mycoplasma, Pasteurella, 
Pseudomonas spp., Chlamydia. • Vagina is 
not a sterile environment; culture of normal 
bitches results in growth of normal vaginal 
flora; use of vaginal cytology is essential for 
• Performed in conjunction with vaginal 
culture. • Juvenile vaginitis: usually 
polymorphonuclear leukocytes ± bacteria. 
• Adult-onset vaginitis—usually septic 
inflammation. • Evaluate epithelial cells for 
cornification—cornification present under 
the influence of estrogen. • Determine nature 
of discharge—inflammatory, blood, presence 
of fecal material.
• Using rigid cystourethroscope, uretero -
scope, pediatric gastroscope, proctoscope, 
or flexible endoscope. • Identify anatomic 
anomalies, evaluate vaginal mucosa. • Identify 
source of vaginal discharge. • Remove foreign 
body, biopsy masses. • The vaginal wall can 
be thin in ovariectomized bitches—exercise 
care when using rigid cysto-urethroscope and 
ureteroscope.
Other
• Digital vaginal examination—identify 
strictures in posterior tract. • Histopathology 
of vaginal masses. • Urine culture and 
  TREATMENT
• Correction/removal of underlying cause. 
• Generally outpatient. • Surgical management 
may be necessary for foreign bodies, masses, or 
correction of structural anomalies. 
• Elizabethan collars to prevent self-mutilation.
ACTIVITY
Not altered.
DIET
General
• B. canis -positive patients should be isolated. 
Euthanasia recommended due to zoonotic 
potential and lack of effective treatment. 
• Exogenous estrogens and androgens must 
be removed from the environment.

1398  Blackwell’s Five-Minute Veterinary Consult  
VJuvenile Vaginitis
• Generally resolves without treatment. 
• Should resolve after first estrous cycle, if not 
before. Patient may need to go through one 
estrous cycle prior to elective OHE.
• Usually occurs secondary to underlying 
cause, and resolves after correction. • If no 
primary cause identified, high likelihood of 
spontaneous recovery without treatment.
• Correction of structural anomaly. • Removal 
of foreign body. • Removal/biopsy of vaginal 
mass. • Episioplasty. • Vaginectomy may be 
performed in refractory cases.
• Antibiotic therapy warranted in patients 
with excessive discomfort (pain or excessive 
vulvar licking) and/or urinary tract infections. 
• Antibiotic selection based on culture and 
sensitivity combined with vaginal cytology. 
• Probiotics—helpful to restore normal 
vaginal flora.
• Systemic antibiotics (type based on cranial 
vaginal culture and sensitivity); treat for 4 
weeks. • Nonsteroidal anti-inflammatory 
drugs (NSAIDs) or anti-inflammatory dose of 
corticosteroids to decrease inflammation. 
• Diethylstilbestrol (DES)—for idiopathic or 
recurrent vaginitis in spayed bitches; restores 
normal mucosal integrity, increases vaginal 
epithelial cornification; use lowest effective 
dose: 0.5 mg, PO for dogs weighing <9 kg or 
1 mg PO for dogs >9 kg q24h for 7 days, 
then taper dose over 2–4 weeks and maintain 
at lowest effective dose. Potential lifelong 
therapy: ◦ Incurin® (estriol) used as above. 
• Probiotics—to restore normal vaginal flora. 
Potential lifelong therapy.
• Antibiotic therapy in patients may result in 
alteration of normal flora, development of 
infection secondary to treatment, or foster 
drug-resistant bacteria. • Vaginal douches with antibiotic/antiseptic agents may be 
irritating to the vaginal mucosa and worsen 
the condition. • Corticosteroid administration 
may worsen concurrent infections.
Estrogen administration may increase risk of 
pyometra in intact animals.
Effects of hydrocortisone may be potentiated 
with concurrent estrogen therapy.
• Juvenile vaginitis may be treated with DES 
to induce estrus in refractory cases, but long- 
term effects are not documented. • Moist 
towelettes/baby wipes may be used to clean 
the perivulvar area.
  FOLLOW-UP
• Reevaluate if symptoms become more 
severe or intolerable. • Reevaluate after first 
• Recheck if symptoms do not resolve after 
removal of underlying cause. • Reculture 5–7 
days after cessation of antibiotic therapy or if 
symptoms continue despite therapy.
• Delay elective OHE until after first estrous 
cycle in dogs with juvenile vaginitis. • Avoid 
using antibiotics if unwarranted. • Maintain 
good body weight and condition. • Avoid 
vaginal douching. • Avoid exogenous 
androgen therapy.
• Juvenile vaginitis—onset at 6 weeks to 
6–12 months of age; duration is days to 
months but typically intermittent; usually 
resolves with time or after first estrous cycle. 
• Adult-onset—normally resolves after 
removal/treatment of inciting cause; 
antibiotic therapy may hasten resolution in 
some cases, NSAIDs may help resolve 
inflammation.  MISCELLANEOUS
• Perivulvar dermatitis. • Atopy.
Juvenile vaginitis may be present in 
prepubertal dogs, usually <1 year of age.
Brucella canis —uncommon cause but should 
• Vaginitis during pregnancy is rare but may 
result in ascending infection and subsequent 
abortion. Resolution of vaginitis should result in 
a good prognosis for fertility if underlying cause 
does not affect fertility. • Structural anomalies 
such as persistent hymen may prevent natural 
mating to occur, or could predispose to a 
dystocia if artificially inseminated. • Scarring 
secondary to trauma may result in excessive 
fibrous tissue and decreased distensibility of 
the vagina.
SEE ALSO
drug.
• TVT = transmissible venereal tumor.
Johnson CA. Diagnosis and treatment of 
chronic vaginitis in the bitch. Vet Clin 
North Am 1991, 21:523–531.
Parker NA. Clinical approach to canine 
vaginitis: a review. Theriogenology 1998, 
112–115.
available onlineVaginitis  (continued)

Canine and Feline, Seventh Edition  1399
VVascular Ring Anomalies
  BASICS
OVERVIEW
Right Aortic Arch
• Entrapment of the esophagus by a persistent 
right fourth aortic arch (PRAA) on the right 
and dorsally, the base of the heart and 
pulmonary artery ventrally, and ductus or 
ligamentum arteriosum on the left and dorsally.
• Causes megaesophagus cranial to the 
obstruction at the base of the heart.
Double Aortic Arch
• Entrapment of the esophagus by a functional 
aortic arch on the right, an atretic aortic arch 
on the left, the base of the heart and pulmonary 
artery ventrally, and ductus or ligamentum 
arteriosum on the left and dorsally.
obstruction at the base of the heart; also 
causes some tracheal compression.
• Seen most commonly in German shepherd 
dogs, Irish setters, Great Danes, and Boston 
terriers.
SIGNS
• Regurgitation of undigested solid food in 
animals <6 months old.
• Malnourishment in many animals.
• Time between eating and regurgitation varies.
• Signs of aspiration pneumonia (e.g., cough, 
tachypnea, or dyspnea) in some animals.
N/A
  DIAGNOSIS
• Congenital megaesophagus.
• Stricture, diverticulum, or esophageal 
• Esophageal motility disorder in shar-peis.
• High white blood cells in some animals 
N/A
IMAGING
• Thoracic radiography—shows food-filled 
cranial esophagus or signs of aspiration 
pneumonia in some animals.
• Contrast esophagography—confirms 
megaesophagus extending to the heart base.
• Fluoroscopy—may be used to differentiate 
esophageal motility disorders.• Angiography—may be needed to differenti-
ate between specific vascular ring anomalies.
Esophagoscopy can be used to differentiate 
esophageal motility disorders.
  TREATMENT
• Surgical correction of the vascular entrapment 
is indicated—can be performed thoracoscopically 
or by thoracotomy with similar results.
• Medical management of concurrent 
aspiration pneumonia may be necessary.
• Feeding procedures for megaesophagus may 
also be necessary for a prolonged period.
• Supportive care with oxygen may be needed 
in animals with aspiration pneumonia.
Broad-spectrum antibiotics, such as 
enrofloxacin 2.5 mg/kg q12h and amoxicillin 
10–15 mg/kg q12h should be instituted in 
animals with aspiration pneumonia.
N/A
  FOLLOW-UP
• Prognosis for resolution of the problem, 
even after surgery, is guarded. However, the 
majority of dogs that survive longer than 2 
months post repair of PRAA have a good to 
excellent outcome.
• Complications of malnourishment and 
aspiration pneumonia are common and can 
be severe.
• Esophageal function may be permanently 
• PRAA = persistent right fourth aortic arch.
NS, eds., Textbook of Canine and Feline 
Saunders, 1999, pp. 471–535.
Krebs IA, Lindsley S, Shaver S, et al. 
Short- and long-term outcome of dogs following surgical correction of persistent 
right aortic arch. J Am Anim Hosp Assoc 
2014, 50:181–186.
Parks MK. Park’s Pediatric Cardiology for 
Practitioners, 6th ed. Philadelphia, PA: 
Elsevier Saunders 2014, pp. 307–313.
Author  Jean M. Betkowski

1400  Blackwell’s Five-Minute Veterinary Consult  
VVasculitis, Cutaneous
  BASICS
OVERVIEW
• Inflammation of blood vessel walls.
• Pathophysiology —primarily type III 
(immune complex), but type I and type II 
reactions possible.
• Systems affected—skin/exocrine and renal/
urologic in some greyhounds.
• Genetics—familial pyogranuloma and 
vasculitis of Scottish terriers possibly 
autosomal dominant; proliferative arteritis in 
St. Bernards (unknown mode of inheritance).
Species
Dog and cat (rare).
Chinese Shar-Pei, dachshund, collie, Shetland 
sheepdog, German shepherd dog, and 
Rottweiler predisposed.
SIGNS
Anorexia, depression, pyrexia possible.
• Focal alopecia with scarring and scaling 
(especially vaccine-induced)—lesions over 
location of vaccination and pinnal apices.
• Necrosis and punctate ulcers, palpable 
purpura, hemorrhagic bullae or urticaria.
• Acrocyanosis.
• Extremities (paws, pinnae, lips, tail, and 
oral mucosa) may be painful.
• Pitting edema of the extremities, polyarthro -
pathy, and myopathy possible.
• Vaccine-induced.
• Adverse food reaction.
• Tick-borne diseases (e.g., Rickettsia rickettsii ).
• Infectious.
• Underlying metabolic process (e.g., diabetes).
  DIAGNOSIS
• Deep pyoderma.
• Chemical and thermal burn.
• Hypersensitivity reaction.
• Cryoglobulinemia.
• Toxic epidermal necrolysis.
• Eosinophilic dermatitis.
• Systemic lupus erythematosus.• Bullous pemphigoid.
• Pemphigus vulgaris.
• Sepsis.
Normal unless due to underlying metabolic 
process or infection.
• Serologic testing for parasitic and infectious 
disease.
• Immunodiagnostics—antinuclear antibody 
(ANA) titer, Coombs’ test, and cold agglutinin 
tests.
• Biopsy of early lesion—neutrophilic (leuko  - 
cytoclastic/non-leukocytoclastic), lympho -
cytic, eosinophilic, or granulomatous mixed 
cells in and around the vessels; vascular 
necrosis and fibrin thrombi may be promi -
nent; perivascular hemorrhage and edema 
may occur.
• Representative cultures (e.g., blood, urine, 
skin) if suspicious of infectious issues.
• Subtle findings suggestive of follicular, 
dermal, and/or epidermal hypoxia may be 
seen in mild cases or late-stage tissue samples.
• May vary with stage and etiology.
• Intramural inflammation of vessels, endothelial 
cell swelling, pale collagen, faded hair follicles, 
hemorrhage, and edema of surrounding tissue.
  TREATMENT
• Adequate wound care may be necessary for 
cases with severe and extensive ulceration.
• No limitation in activity unless infectious 
agent suspected.
• Isolate if contagious or zoonotic agent 
• Individual (focal) lesions may be surgically 
excised; otherwise, dependent on underlying 
etiology.
• Based on underlying disease; if drugs or 
drug-like substances are suspected, they 
should be discontinued.
• Immune-mediated disease with concurrent 
vasculitis—prednisolone 0.5–4 mg/kg q24h, 
taper with response.
• Pentoxifylline 10–20 mg/kg PO q8–12h.
• Cyclosporine 5 mg/kg q24h.
• Tetracycline and niacinamide each 500 mg 
q8h for dogs >10 kg or 250 mg PO q8h for 
dogs <10 kg or doxycycline 5 mg/kg PO 
q12h with niacinamide as with tetracycline.Alternative Drugs
• Chlorambucil 0.1–0.2 mg/kg every 1–2 days 
PO initially and taper according to response.
• Azathioprine 1–2 mg/kg every 1–2 days PO 
initially and taper according to response.
• Dapsone 1 mg/kg PO q24h or sulfasalazine 
15–22 mg/kg PO q8–12h.
• Do not use any medications suspected of 
causing hypersensitivity.
• Do not administer tetracycline/doxycycline 
to pregnant or young animals.
  FOLLOW-UP
• Monitor appropriately during treatment of 
specific etiology.
• Pentoxifylline—may decrease blood pressure; 
may cause excitation; monitor blood pressure 
if concerned.
• Doxycycline or tetracycline—possible increased 
liver enzymes, possible esophageal strictures in 
cats (doxycycline); monitor liver chemistries.
• Patients receiving prednisolone, azathioprine, 
chlorambucil, sulfasalazine, or dapsone—
monitor appropriately with CBC, chemistry 
screen, and urinalysis.
• Sulfasalazine or dapsone—may decrease 
tear formation; Schirmer tear test every 2 
weeks initially and then routinely.
• Immunosuppressive therapies should be 
reduced to the lowest possible therapeutic dose.
Sepsis and death from primary cause and/or 
sequelae if severe.
If no underlying disease is found, vasculitis 
may be difficult to treat and the prognosis is 
guarded.
• Corticosteroids, sulfasalazine, tetracycline/
doxycycline, and dapsone—do not use in 
Innera, M. Cutaneous vasculitis. Vet Clin North 
Am Small Anim Pract 2013, 43:113–134.
Resnick

Canine and Feline, Seventh Edition  1401
VVasculitis, Systemic (Including Phlebitis)
  BASICS
• Heterogeneous group of disorders causing 
inflammation secondary to endothelial 
damage of blood vessel walls, leading to tissue 
necrosis.
• Characterized by histological evidence of 
inflammation, destruction of blood vessels 
and ischemic changes.
• Phlebitis is associated with, and is a 
complication of, IV therapy with the tunica 
intima of the vascular endothelial wall 
becoming inflamed.
• Endothelial damage by an infectious agent, 
parasite infestation, endotoxin, or immune 
complex deposition that initiates local 
inflammation, neutrophil chemotaxis, and 
complement activation, sensitizing the 
vascular endothelium causing release of 
vasoactive substances that cause 
vasoconstriction, increase vascular 
permeability, and activate coagulation systems.
• End result is endothelial cell activation, 
necrosis of the vessel wall with subsequent 
thrombosis which may cause hemorrhage and 
extravasation of proteins into surrounding 
tissue, leading to swelling and edema.
• Thrombosis obstructs blood flow and may 
cause palpable thickening or vascular cord, which 
may progress to irreversible vascular sclerosis.
• Leukocyte pyrogens may cause systemic 
inflammation and fever.
• Skin—local inflammation/infection.
• Cardiovascular—altered vascular 
permeability and blood flow.
• Hemic/lymphatic/immune—bacteria, 
inflammatory mediators and emboli can 
cause systemic inflammatory response and 
organ dysfunction.
• Renal/urologic—systemic inflammatory 
response and type III hypersensitivity 
reaction. causing proteinuria and glomerulo­
nephritis, respectively.
• Ophthalmic—uveitis due to systemic 
• Musculoskeletal—systemic inflammatory 
reaction.
• Respiratory—deep venous thrombophlebitis 
may cause pulmonary embolism.
• Unknown—vascular inflammation is a 
common cause of dermatologic disease in 
humans and animals. More often seen in dogs 
than in cats.
• 20–80% of hospitalized patients receiving 
peripheral IV therapy develop phlebitis with 
superficial thrombophlebitis most common (10–12% may progress to deep venous 
thrombosis).
Species
• No known specific age or gender 
predisposition in veterinary medicine.
• Collies and Shetland sheepdogs (familial 
canine dermatomyositis).
• German shepherd dog—autosomal recessive.
• Scottish terrier—suspect autosomal dominant.
• Shar­pei—familial vasculitis.
• St. Bernard and giant schnauzer—dermal 
arteritis of nasal philtrum.
• Jack Russell terrier.
• Greyhound—idiopathic cutaneous and 
renal vasculopathy.
SIGNS
• Provocative drug (e.g., cephalexin, 
sulfonamides, itraconazole, and hydralazine) 
given to sensitized animal.
• Recent vaccination history.
• Poor dirofilariasis prophylaxis in endemic 
areas.
• Swelling.
• Palpable purpura, plaques, hemorrhagic 
bullae alone or in combination with edema.
• Necrosis of affected skin, especially mucous 
membranes, mucocutaneous junctions, 
pinnae edges, and footpads.
• Systemic signs reflecting organ involvement 
(e.g., hepatic, renal, gastrointestinal and CNS).
• Systemic signs of illness (e.g., lethargy, 
anorexia, lymphadenopathy, pyrexia, 
generalized pain, and weight loss).
• Juvenile polyarteritis in beagles characterized 
by recurring episodes of fever (>40°C) and 
neck pain persisting for 3–7 days.
• Cutaneous lesions of polyarteritis nodosa 
(subcutaneous nodules—less common in 
dogs than in people).
• Signs associated with underlying infectious 
or immune ­related disease (e.g., thrombo­
cytopenia and polyarthropathy).
• Ophthalmologic examination—anterior 
uveitis, scleral injection, hyphema.
CAUSES
• Parasitic—Dirofilaria immitis, 
Angiostrongylus vasorum, Leishmania spp., 
Babesia gibsoni.
• Viral—e.g., feline infectious peritonitis, canine 
coronavirus, and canine circovirus infection.
• Rickettsial—e.g., Rocky Mountain spotted 
fever and ehrlichiosis.
• Protozoal—e.g., Toxoplasma.
• Bacterial—sepsis.Iatrogenic
• Mechanical injury from IV catheter size/
stiffness/integrity/duration, traumatic 
placement, previous venipuncture, high fluid 
infusion rates.
• Chemical injury—IV catheter material, 
drugs, fluids of extreme osmolality or pH, 
parenteral nutrition, other vesicant solutions.
• Obstructed blood flow—large ­bore 
catheter, vasoconstriction, and hypotension.
Approximately 50% of cases.
Immune-Related
• Rheumatoid arthritis ­like arthropathy.
• Lupus ­like drug reaction.
• Type III hypersensitivities (e.g., to food, 
cephalexin, sulfonamides, fenbendazole, and 
penicillin).
• Wegener’s granulomatosis (rare).
• Polyarteritis nodosa.
• Uremia.
  DIAGNOSIS
• Cutaneous signs developing after 
administration of medication/vaccine 
implicate drug reaction (usually not 
immediate, may develop after days or weeks).
• Vasculitis associated with systemic signs 
(e.g., polyarthropathy, myositis, pyrexia) 
implicates immune or infectious cause.
• Cold hemagglutinin disease suggested by 
distribution of cyanotic or necrotic lesions 
(nose, ears, toes, tail tip, prepuce) and history 
of exposure to cold.
• CBC changes consistent with degree of 
systemic inflammatory response and platelet 
• Biochemistry and urinalysis changes may be 
applicable with organ involvement (e.g., hepatic, 
renal, portal, caval, gastrointestinal, cerebral, 
cardiac, and pulmonary).
• Tissue, blood, and urine cultures if sepsis 
• Serologic tests may aid diagnosis of 
infectious (i.e., rickettsial, Leishmania ) 
disease.
• Antinuclear antibody (ANA) titer positive 
in patients with systemic lupus erythematosus 
(SLE); may also be positive in patients with 
other systemic illnesses.
• Occult heartworm test positive in patient 
with dirofilariasis.
• Angiostrongylus  infestation diagnosed by 
fecal examination and cytologic examination 
of tracheal wash.

1402  Blackwell’s Five-Minute Veterinary Consult  
V• Coagulation—may see alterations in 
prothrombin time (PT), partial thromboplastin 
time (PTT), D ­dimer, antithrombin, protein 
C, thromboelastography.
IMAGING
Nonspecific abnormalities that may be seen 
include infiltrates, nodules, patchy consolidation, 
pleural effusion, and cardiomegaly.
Abdominal Imaging
• CT (with angiogram) or MRI— Provide 
valuable information regarding diagnosis of 
deep tissue embolism and thickening of the 
vessel wall when suspected based on organ 
damage or dysfunction.
• B­mode ultrasonography to assess venous 
patency, character, and blood flow.
• Doppler assessment—inexpensive test of 
venous patency and blood flow.
• Skin biopsy specimen from active edges of 
developing lesions is definitive for vasculitis 
but may not reveal cause.
• Immunofluorescence test of skin biopsy 
specimen may rule out pemphigus and 
pemphigoid diseases.
• If allergic response is suspected, resolution 
of signs upon discontinuation of suspect 
medication or food supports diagnosis.
• Inflammation and destruction of blood vessels 
with secondary ischemic/hypoxic changes from 
thromboembolic occlusion of vessels.
• Inflammatory infiltrate may be neutrophilic 
(major), eosinophilic, or lymphocytic.
• Damage to blood vessels may lead to the 
development of hemorrhage and edema 
within affected tissue.
• Epidermal lesions such as exudation, 
crusting, and ulceration may also develop 
secondary to ischemia.
  TREATMENT
• Based upon individual patient, history, 
clinical findings, identification of the inciting 
cause, and whether or not disease is 
• Remove suspected inciting cause (IV 
catheter, drugs, or xenobiotic substances) and 
avoid in the future.
• Minimally affected dogs require little 
• Moderate to severe cases require pharma­
cologic intervention and wound care to prevent 
secondary bacterial infection and sepsis.
• If untreatable or unknown underlying 
condition—glucocorticoid, immunosuppressive (e.g., cyclophosphamide, 
azathioprine), and other drugs (e.g., dapsone 
and sulfasalazine) are occasionally effective, 
but clinical trials of efficacy have not been 
reported in animals.
• If caustic infiltration suspected for phlebitis, 
terminate infusion and leave cannula in place 
temporarily to aspirate residual catheter fluid 
and instill specific antidotes into affected 
tissue when applicable.
• Intermittent warm moist compress or 
hydrotherapy; some extravasated substances 
require cold therapy.
• Photobiomodulation (low ­level light 
therapy [LLLT]) can be used directly over 
affected areas to reduce inflammation, 
activate stem cells, and promote blood flow 
and tissue repair.
• Avoid stagnant blood flow and thrombo­
embolism by promoting mobility (i.e., physical 
therapy and/or compression therapy).
• Supportive therapy (e.g., IV fluids, oxygen, 
nutrition) for systemic illness secondary to 
vasculitis (e.g., hepatic, renal, pulmonary, 
gastrointestinal, cerebral, cardiac).
• IV catheter placement and maintenance—
use strict aseptic technique and sterile 
dressing with IV catheters being regularly 
checked for patency, line integrity, and 
associated swelling (every 1–2 hours) with 
continuous infusions. Change peripheral 
catheters every 3–4 days, or within 
24 hours if placed under emergency 
ACTIVITY
• Soft/cushioned bedding and protective 
footwear can be used when the pads are 
eroded/ulcerated.
• Minimal rough play with other dogs as may 
exacerbate skin damage.
DIET
• Nutritional support appropriate to 
treatment of underlying illness(es).
• Consider glycemic control if sepsis or risk 
of sepsis.
• Advise clients of IV catheter risks and 
complications, especially in patients with 
• Clients should be trained in and continue 
physical therapy and basic nursing care at 
home.
• Infected catheter sites and/or extensive 
tissue damage may require surgical 
debridement and delayed closure.
• Surgical ligation or stripping of the corded 
vessels may be indicated to avoid deep vein 
thrombosis.  MEDICATIONS
• Infectious or immune ­related—treat 
underlying disease (see specific condition); 
• Lupus ­like drug reactions and type III 
hypersensitivity—discontinue drug; 
• Methylxanthine derivative—pentoxifylline 
20 mg/kg three times daily improves micro­
circulatory peripheral blood flow, tissue blood 
oxygenation, and decreases inflammation.
• Glucocorticoids—prednisolone 0.5–1 mg/
kg with progressive disease and no underlying 
trigger identification; continue until clinical 
remission achieved then slowly taper by 25% 
every 14 days.
• Other immunomodulators—cases 
refractory to glucocorticoids (e.g., cyclo­
sporine, azathioprine, chlorambucil).
• Antioxidants—e.g., vitamin E 200–800 IU 
q12h anecdotally provide a protective effect 
against ischemic dermatopathies.
• Leukocyte ­specific anti ­inflammatory—
tetracycline and niacinamide combination 
used for milder cases of vasculitis; exact 
mechanism incompletely understood.
• Sulfonamide drugs—e.g., sulfasalazine 25 
mg/kg three times daily for refractory 
neutrophilic vasculitis.
• Antibiotics (if infection/sepsis suspected)—
use empirical therapy, based on location and 
potential contaminants if no culture and 
sensitivity available.
• Avoid caustic, irritating, or immunogenic 
topicals or infusions.
• Do not administer sulfasalazine to patients 
sensitive to sulfonamides.
• Multiple myelosuppressive/immunosuppressive 
drugs may be additive and increase risk of 
• Avoid use of systemic nonsteroidal 
anti­inflammatory drugs (NSAIDs) if renal, 
hepatic, or gastrointestinal dysfunction.
• Corticosteroids, unless used as an 
appropriate pretreatment for chemotherapy, 
are associated with delayed wound healing 
and may predispose to infection.
• Pentoxifylline may reduce blood pressure.
Use of NSAIDs with concurrent anti ­
inflammatory or immunosuppressive dose 
• Topical dermatitis creams (e.g. silver ­
sulfadiazine) may help reduce irritation and 
prevent infection.Vasculitis, Systemic (Including Phlebitis)  (continued)

Canine and Feline, Seventh Edition  1403
V• Topical tacrolimus for focal lesions may 
  FOLLOW-UP
• Patients being treated with sulfonamide 
drugs (e.g., dapsone) or immunosuppressants–  
regular monitoring of CBC, serum chemistry 
profile and urinalysis for side effects (e.g., 
myelosuppression, hepatopathy, and other 
blood dyscrasias).
• Patients receiving sulfasalazine—monitor 
for keratoconjunctivitis sicca with Schirmer 
tear test (every 2 weeks for first 2 months).
• Hardness, skin pallor, black discoloration, 
or eschar formation occur with tissue 
necrosis.
• Persistent or progressive redness, swelling, 
pain, or heat—adjust antibiotic therapy based 
on most current culture and sensitivity 
results.
• Tick prevention and regular monitoring of 
serum titers for tick ­borne diseases in 
• Avoidance/elimination of optional/
minimizing of the number of vaccines given 
at any one time.
• Discontinue and avoid suspected inciting 
triggering factors.
• Avoid use of phlebotic veins for IV therapy 
or blood collection until completely healed.• Consider using submicron IV catheter 
filters, which may reduce incidence by 
removing particulates, endotoxin, and other 
soluble mediators of morbidity.
• Dependent on severity.
• Organ damage (e.g., hepatic, renal, portal, 
caval, gastrointestinal, cerebral, cardiac, 
pulmonary).
• Lymphangitis.
• Extension to deep venous system.
• Mild phlebitis cases self ­limiting (1–3 days) 
with removal of catheter. For severe local 
lesions, resolution can take 3–4 weeks and may 
result in loss of function/permanent tissue 
damage. Poor prognosis when associated with 
pulmonary thromboembolism and/or sepsis.
• Infection/cellulitis/sepsis.
• Immune ­mediated disease (e.g., SLE).
• Neonatal and geriatric patients may be 
predisposed to infection.
• Delayed wound healing in geriatric patients.ZOONOTIC POTENTIAL
N/A
• Pregnancy may predispose  to 
• Incidence of fetal complications with 
phlebitis is unknown.
SYNONYMS
• Thrombophlebitis.
SEE ALSO
• Lupus Erythematosus, Systemic.
• LLLT = low ­level light therapy.
drug.
https://www.dvm360.com/view/
diagnosing ­and­managing ­canine ­cutaneous ­
vasculitis ­proceedings
Innera M. Cutaneous vasculitis in small 
Pract 2013, 43:113–134.
Consulting Editor  Michael Aherne(continued)  Vasculitis, Systemic (Including Phlebitis)

1404  Blackwell’s Five-Minute Veterinary Consult  
VVentricular Arrhythmias and Sudden Death in German Shepherds
 BASICS
OVERVIEW
Inherited disorder resulting in ventricular 
arrhythmias in otherwise healthy young 
German shepherd dogs. The phenotypic 
spectrum is wide, with some dogs having 
infrequent single premature ventricular 
complexes while others have frequent and rapid 
ventricular tachycardia (VT) that is associated 
with sudden death. The pattern of inheritance 
is complex, depending heavily on background 
genetics. Siblings of dogs that have died 
suddenly should be tested for this disorder.
• Most dogs develop arrhythmias at approx  - 
imately 12 weeks of age (identified as young 
as 6 weeks). Number and severity of 
arrhythmias tend to peak between 5–9 
months. By approximately 18–24 months 
most dogs have only a few arrhythmias.
SIGNS
• Signs are very rare (e.g., in >500 dogs 
examined only 1 had syncope) since VT is often 
nonsustained until, in some dogs, it degenerates 
into ventricular fibrillation resulting in death 
(usually between 5 and 9 months of age).
• Arrhythmias often detected during routine 
examination before neutering. • Death is 
associated with sleep, rest after exercise, or 
excitement after sleep, particularly in early 
morning.
• Genetic mutation(s) responsible has not 
been identified. • Multiple electrophysiologic 
abnormalities have been identified—early and 
delayed afterdepolarizations, heterogeneous 
and altered action potential duration, as well 
as changes in ion channel current density, 
calcium cycling, and sympathetic innervation.
• VT tends to be most frequent with slow heart 
rates (drug-induced [e.g. fentanyl] or during sleep).
 DIAGNOSIS
Rule out myocarditis.
Results of routine laboratory tests are 
T roponin concentration—to rule out 
myocarditis. Dogs with inherited arrhythmias 
have normal troponin levels.
IMAGING
• Thoracic radiographs—normal.
• Echocardiography—usually normal.DIAGNOSTIC PROCEDURES
24-Hour Ambulatory Electrocardiogram 
(Holter Monitor)
• Required for diagnosis and classification of 
severity. • Arrhythmias identified most com -
monly are rapid (rates >400 bpm) polymorphic 
VT with single premature complexes that are 
most commonly of a left ventricular origin 
pattern (negative in lead II). Though nonsus -
tained rapid polymorphic VT is most characteris -
tic, approximately 15% of dogs will have slower 
monomorphic and more sustained VT. • Some 
dogs will have thousands of singlet ventricular 
premature complexes (VPCs) with no VT; 
extensive periods of ventricular bigeminy have 
been found in others. • After 6 months of age, 
runs of VT are more common after pauses.
Routine gross and histopathologic examina-
tion is within normal limits.
 TREATMENT
• Limited studies have shown cardiac pacing 
to keep the heart rate above 120 bpm 
decreased the frequency of the arrhythmias 
but did not prevent sudden death.
• Implantation of cardioverter defibrillators 
may be helpful, but proper programming of 
these devices in young dogs is complicated.
• Avoid drugs that slow heart rate.
• Anesthesia is not contraindicated as long as 
anticholinergic drugs are used to prevent 
bradycardia during the age range when the 
arrhythmias exist. • T reatment is required 
only for dogs with VT. Afflicted dogs with 
only VPCs do not die. However, if a young 
dog is identified with this disorder, repeated 
Holter monitoring is advised to be sure that 
the phenotype of that particular dog does not 
include VT (e.g., particularly if the peak 
affectedness of that dog has not yet occurred).
• Ventricular arrhythmias usually are easily 
suppressed with lidocaine 2 mg/kg IV.
• Control of the arrhythmias with oral 
medication is more problematic. • Sotalol 
alone can be proarrhythmic and should not be 
used. • Sotalol 2–3 mg/kg PO q12h combined 
with mexiletine 4–8 mg/kg PO q8h supp -
resses the ventricular arrhythmias, but 
response in individual dogs is highly variable.
• Avoid drugs that slow heart rate until dogs 
are older than 18–24 months.• Drugs that slow or prolong action potential 
duration such as sotalol, phenylephrine, or 
fentanyl are proarrhythmic.
 FOLLOW-UP
• Repeat Holter monitoring to assess drug 
efficacy. • After 18–24 months of age the 
Holter monitoring is again repeated. If the 
number of ventricular ectopic complexes is 
<2,000 singles with no VT, the dog’s risk of 
death is very low and medications may be 
stopped. • Although occasional dogs may have 
a dramatic drop in the arrhythmia count and 
severity during treatment, most do not. 
Therefore, absence of arrhythmias on Holter 
recordings after 18–24 months of age 
indicates a change in the disorder rather than 
an antiarrhythmic effect.
• Lifelong treatment is not required.
• Approximately 50% of affected dogs with 
>10 runs of VT/24 hours will die suddenly 
before 1 year of age. If a dog does not have 
VT identified by 24-hour electrocardio-
graphic monitoring, the probability of death 
is very low. • Even severely affected dogs that 
have reached the age of 2 years with 
documented absence of arrhythmia have lived 
a normal lifespan >12 years.
Since identification of affected dogs depends 
on the determination of arrhythmias before 
the age of 1 (ideally 4–9 months) to 2 years 
(at most), afflicted dogs can easily be missed 
because the only clinical sign is sudden death 
with no evidence of a cause found on routine 
post-mortem examination.
• VPC = ventricular premature complex.
• VT = ventricular tachycardia.
2016.
N. Sydney Moïse.

Canine and Feline, Seventh Edition  1405
V
  BASICS
• A ventricular rhythm of disorganized 
electrical activity resulting in nonproductive 
ventricular muscle quivering (i.e., fibrillation). 
• Also known as V-fib or VF and is considered 
the most severe cardiac rhythm disturbance.
Loss of organized ventricular activity results 
in acute and profound drop in cardiac 
output, systemic blood pressure, and organ 
perfusion, eventually leading to death.
• Cardiovascular. • All organ systems affected 
by loss of perfusion.
GENETICS
• Not recognized in veterinary patients. 
• However, there are known ventricular 
arrhythmias with modes of inheritance in the 
dog.
Unknown
Species
None
Unknown, but probably more common in 
geriatric animals.
SIGNS
• Severe systemic illness. • Severe cardiac 
disease. • Previously documented cardiac 
• Collapse. • Loss of consciousness (i.e., 
syncope). • Cardiac arrest. • Death.CAUSES
Cardiac
• Cardiac surgery/interventional procedure. 
• Cardiomyopathy. • Myocardial injury. 
• Myocarditis. • Subaortic/aortic stenosis.
Extracardiac
• Anoxia. • Autonomic imbalances, 
especially high sympathetic tone or 
administration of catecholamines. 
• Circulatory shock. • Drug reactions—e.g., 
anesthetic agents, especially halothane and 
ultrashort-acting barbiturates, digoxin. 
• Electrical shock. • Electrolyte and acid–
base imbalances. • Hypothermia.
Any severe systemic illness or cardiac disease.
  DIAGNOSIS
ECG Features (Figures 1 and 2)
• Rapid, chaotic, irregular rhythm with bizarre 
waves or oscillations. • Oscillations may be 
large (coarse fibrillation) or small (fine 
fibrillation). • Absent P waves. • Absent QRS 
• Check for pulse. • Rule out ECG artifact. 
• Reapply ECG clips and ensure good skin 
contact and adequate gel (or alcohol) 
applied to leads. • If there is possibility of 
using defibrillator to shock patient, do 
not use alcohol as it is a flammable 
substance.
The abnormalities generally relate to the 
underlying metabolic problem that causes 
ventricular fibrillation.
Cardiac troponin I may be elevated in case of 
severe arrhythmia, cardiac ischemia, or 
myocarditis.IMAGING
• Can utilize point of care ultrasound to 
visualize heart chamber activity. • Avoid alcohol 
and utilize gel whenever possible (see above).
Vary depending on histopathologic findings 
on post-mortem examination.
  TREATMENT
• Rapidly fatal rhythm requiring immediate, 
aggressive treatment. • Outcome is often death 
without use of electrical cardioversion 
(defibrillation).
Direct Current Defibrillation
• Immediate defibrillation is recommended 
when the duration of cardiopulmonary arrest 
caused by ventricular fibrillation is 4 minutes 
or less. • Otherwise, a 2-minute cycle of chest 
compressions before defibrillation is 
recommended. • The dose of energy for initial 
defibrillation is 2–4 J/kg (biphasic defibrillator) 
or 4–6 J/kg (monophasic defibrillator). • If an 
initial shock is not successful, CPR is resumed 
for 2 minutes before defibrillation is attempted 
again. • A 50% escalation in the energy 
delivered may be considered for subsequent 
defibrillation attempts.
Precordial Thump
To be used if no access to an electrical 
defibrillator. • Apply a sharp blow with the 
ulnar aspect of a closed fist to the chest wall 
over the heart. • Rarely successful in 
conversion to sinus rhythm. • This technique 
is not recommended for other rhythms as a 
thump can also cause more malignant 
T reat any identified conditions such as 
hypothermia, electrolyte disturbances, and 
acid–base disorders.Ventricular Fibrillation
Figure 1 .
Coarse ventricular fibrillation. (Source: From Tilley LP . Essentials of Canine and Feline Electrocardiography, 3rd ed. Baltimore: Williams & Wilkins, 1992. Reprinted 
with permission of Wolters Kluwer.)

1406  Blackwell’s Five-Minute Veterinary Consult  
VCLIENT EDUCATION
If the patient is converted back to a sinus 
rhythm, warn the owner that the patient is at 
high risk for recurrence of the arrhythmia in 
the immediate post-resuscitation period.
N/A
• Institute cardiopulmonary cerebral 
resuscitation. • Epinephrine—low dose 
(0.01 mg/kg) of epinephrine is recommended 
as high-dose therapy has not been associated 
with increased survival. A shortcut to 
calculate low-dose epinephrine volume for 
administration is 0.1 mL/10 kg. The dose 
may be repeated at 3- to 5-minute intervals. 
• Vasopressin—there is evidence that this 
drug may be equivalent to or even superior to 
epinephrine is some situations. The dose of 
vasopressin is 0.8 units/kg (dogs and cats), 
and the dose may be repeated at 3- to 5-minute 
intervals. • Once the animal is successfully 
converted, administer IV lidocaine or 
amiodarone to lower the risk of refibrillation 
or development of ventricular tachycardia. 
• Lidocaine 2 mg/kg (dogs, IV, IO, IT); a 
shortcut to calculate the dose for the 2% 
(20 mg/mL) solution is 1 mL/10 kg. 
• Amiodarone (Nexterone®) 2–5 mg/kg (dogs, 
IV). Do NOT use amiodarone with polysorbate 
80; this has been shown to cause anaphylaxis in 
dogs. Hypotension is a common occurrence 
during amiodarone administration.
• Lidocaine raises the fibrillation threshold but 
makes defibrillation more difficult. • Lidocaine 
and amiodarone have the potential to be 
proarrhythmic. • There is currently no 
evidence for improved outcome with use of 
these medications in patients with VF .ALTERNATIVE DRUG(S)
• Magnesium (chloride or sulfate) is 
commonly administered (0.3 mEq/kg IV) for 
antiarrhythmic treatment. Magnesium is not 
known to have any proarrhythmic effect. 
There is no supportive evidence for its use in 
VF . • Chemical conversion can be attempted 
if no access to electrical defibrillator. 
Administer 1 mEq potassium/kg and 6 mg/kg 
acetylcholine IC. This approach is rarely 
  FOLLOW-UP
• CBC, biochemistry profile, urinalysis, 
arterial blood gases with acid–base analysis. 
• If primary cardiac disease is suspected—
echocardiogram, cardiac troponin, and 
thoracic radiographs. • Continuous ECG 
Careful monitoring of critically ill patients to 
prevent and correct acid–base disturbances, 
hypotension, and hypoxemia.
• Recurrence of VF . • Death. • Disseminated 
intravascular coagulation. • Multiorgan 
failure.
 EXPECTED COURSE AND  
PROGNOSIS
Most patients die because of either the 
arrhythmia or the underlying disease.
May be more likely in patients of advanced age.
Cardiopulmonary Arrest.
• IC = intracardiac. • IT = intratracheal. 
• VF = ventricular fibrillation.
analysis on veterinary CPR. Part 7: clinical 
22:S102–131.
Kraus MS, Gelzer ARM, Moïse NS. T reatment 
of cardiac arrhythmias and conduction 
disturbances. In: Smith FWK, Tilley LP , 
Oyama MA, Sleeper MM, eds., Manual of 
Thawley JT, Drobatz KJ. Cardiopulmonary 
arrest and resuscitation. In: Smith FWK, 
Manual of Canine and Feline Cardiology, 5th 
ed. St. Louis, MO: Saunders Elsevier, 2016.
Tilley LP , Smith FWK, Jr. 
LP , Oyama MA, Sleeper MM, eds., Manual 
of Canine and Feline Cardiology, 5th ed. St. 
Waldrop JE, Rozanski EA, Swanke ED, et al. 
Causes of cardiopulmonary arrest, resuscita -
tion management, and functional outcome in 
dogs and cats surviving cardiopulmonary 
arrest. J Vet Emerg Crit Care 2004, 14:22–29.
Authors  Anna K. McManamey and Francis 
W.K. Smith, Jr.
Figure 2.
Ventricular flutter–fibrillation in a cat with severe myocardial damage from an 11-story fall. The complexes are very wide, bizarre, tall, and rapid. (Source: From Tilley 
LP . Essentials of Canine and Feline Electrocardiography, 3rd ed. Baltimore: Williams & Wilkins, 1992. Reprinted with permission of Wolters Kluwer.)Ventricular Fibrillation  (continued)

Canine and Feline, Seventh Edition  1407
VVentricular Pre-Excitation and Wolff–Parkinson–White Syndrome
  BASICS
• Ventricular pre-excitation occurs when 
impulses originating in the sinoatrial node or 
atrium activate a portion of the ventricles 
prematurely through an accessory pathway 
without going through the atrioventricular 
(AV) node; the remainder of the ventricles are 
activated normally through the usual 
conduction system. • Wolff–Parkinson–White 
(WPW) syndrome consists of ventricular 
pre-excitation with episodes of paroxysmal 
supraventricular tachycardia (Figures 1 and 2).
ECG Features of Ventricular 
Pre-excitation
• Normal heart rate and rhythm. • Normal P 
waves. • Short PR interval (dogs, <0.06 
seconds; cats, <0.05 seconds). • Widened 
QRS (small dogs, >0.05 seconds; large dogs, 
>0.06 seconds; cats, >0.04 seconds), often 
with slurring or notching of the upstroke of 
the R wave (delta wave).
ECG Features of Ventricular Pre-
excitation with WPW Syndrome
• Extremely rapid heart rate (dogs, often 
>300 bpm; cats, approaching 400–500 bpm). 
• P waves may be difficult to recognize. • QRS 
complexes may be normal, wide with delta 
wave, or very wide and bizarre, depending on 
the circuit. • Conduction is usually 1:1 (i.e., 
1 P wave for every QRS complex).
• Can be associated with congenital or acquired 
cardiac defects in dogs or cats. • May be 
associated with hypertrophic cardiomyopathy in 
cats. • Hemodynamic compromise during 
episodes of supraventricular tachycardia with WPW syndrome. • WPW syndrome results 
from a developmental abnormality of the 
atrioventricular groove. During normal 
cardiogenesis, direct continuity between the 
atrial and ventricular myocardium is lost by 
growth of the annulus fibrosis. Defects in the 
annulus leave muscular connections called 
accessory pathways or Kent bundles between 
the atria and ventricular myocardium. By 
bypassing the AV node, these pathways can lead 
to pre-excitation of the ventricles. • The 
accessory pathways typically have an “all or 
none” conduction properties. They may only 
conduct from the atria to the ventricles (called 
anterograde or antegrade conduction), only 
from the ventricles to the atria (called retrograde 
conduction), or in both directions.
Unknown
Species
SIGNS
• None in patients with ventricular pre-excitation. 
• Syncope in patients with WPW syndrome.
• None in animals with ventricular pre-
excitation. • Rapid heart rate in animals with 
WPW syndrome.
CAUSES
Congenital Heart Disease
• Congenital defect limited to the 
conduction system. • Atrial septal defect in 
dogs or cats. • T ricuspid valvular dysplasia 
in dogs.Acquired Heart Disease
Hypertrophic cardiomyopathy in cats.
  DIAGNOSIS
• Ventricular pre-excitation—differentiate 
from other causes of short PR intervals (e.g., 
fever, hyperthyroidism, and anemia); these 
conditions do not cause delta waves. 
• Narrow complex WPW syndrome—
differentiate from other supraventricular 
arrhythmias (e.g., atrial tachycardia, atrial 
flutter, and atrial fibrillation); WPW 
syndrome is most easily recognized after 
conversion to normal heart rate and rhythm. 
• Alternating WPW syndrome should not be 
confused with ventricular bigeminy. • Wide 
complex WPW syndrome must be 
differentiated from ventricular tachycardia. 
• Short PR interval may be correlated with a 
normal QRS complex if the anomalous 
pathway bypasses the AV node and connects 
to the bundle of His (i.e., Lown-Ganong 
Levine syndrome).
Normal
Normal
IMAGING
Echocardiography may show structural heart 
disease.
• Pathologic findings vary with underlying 
cause. • Possibility of no organic heart 
lesions.
CV6LU
Figure 1 .
Wolff–Parkinson–White syndrome (canine). Ventricular pre-excitation represented by the short PR interval, wide QRS complex, and delta wave (arrow) in CV6LU. 
Paroxysms of supraventricular tachycardia are represented in the long lead II rhythm strip. (Source: From Tilley LP . Essentials of Canine and Feline Electrocardiography, 
3rd ed. Baltimore: Williams & Wilkins, 1992. Reprinted with permission of Wolters Kluwer.)

1408  Blackwell’s Five-Minute Veterinary Consult  
V  TREATMENT
• Ventricular pre-excitation without 
tachycardia—no treatment needed. • WPW 
syndrome requires conversion by ocular or 
carotid sinus pressure, direct current shock 
(the most effective treatment), or drugs.
ACTIVITY
May need to be limited with WPW until 
supraventricular tachycardias are controlled.
WPW—explain the need to identify and treat 
the underlying cause in addition to therapy 
for supraventricular tachycardia.
Catheter ablation with radiofrequency 
current—a relatively recent technique that 
allows accessory pathways to be destroyed or 
ablated by a transvenous catheter positioned 
at the site of the pathway; can be preferred 
alternative to lifelong therapy with drugs.
• A variety of drugs are used in humans; 
opinions differ on agents of choice. 
• Lidocaine 2 mg/kg IV bolus followed by 
25–75 mg/kg/min CRI IV drip (dogs only). • Esmolol 50–100 mg/kg bolus, 50–200 mg/
kg/min CRI (dogs and cats). • Propranolol 
2.5–5 mg PO q8–12h (cats); 0.2–1 mg/kg 
PO q8h (dogs) or atenolol 6.2–12.5 mg PO 
q24h (cats); 0.25–1 mg/kg PO q12h (dogs). 
• Diltiazem may be effective—1–2.5 mg/kg 
PO q8h (cats); 0.5–1.5 mg/kg PO q8h 
(dogs). • Procainamide IV may be used 
acutely because it decreases conduction over 
the accessory pathway and is safe if 
anterograde accessory pathway conduction is 
present in atrial fibrillation.
• Digitalis, verapamil, and propranolol may 
be contraindicated—by slowing conduction 
through the AV node, these drugs may favor 
conduction through the anomalous pathways. 
• Cats—propranolol and atenolol are the 
drugs of choice.
  FOLLOW-UP
Serial ECG.
None expected.
Depends on severity of the underlying cause; 
most WPW patients respond to therapy for 
supraventricular tachycardia—favorable 
• WPW = Wolff–Parkinson–White .
Al-Khatib SM, Pritchett ELC. Clinical 
features of Wolff-Parkinson-White 
syndrome. Am Heart J 1999, 138:403–413.
Hill BL, Tilley LP . Ventricular preexcitation 
in seven dogs and nine cats. J Am Vet Med 
Assoc 1985, 187:1026–1031.
Electrocardiography of the dog and cat. 
Zimetbaum, P . (2016). Cardiac arrhythmias 
with supraventricular origin. In: Goldman 
L, Schafer, AI, eds., Goldman’s Cecil 
Medicine, 25th ed. Philadelphia, PA: 
Saunders, 2016, pp. 356–366.
Figure 2.
Ventricular pre-excitation in a cat with episodes of fainting. The P waves are normal, the PR interval is short, and the QRS complex is wide; delta waves (arrow)  
are present. (Source: From Tilley LP . Essentials of Canine and Feline Electrocardiography, 3rd ed. Baltimore: Williams & Wilkins, 1992. Reprinted with permission of 
Wolters Kluwer.)Ventricular Pre-Excitation and Wolff–Parkinson–White Syndrome  (continued)

Canine and Feline, Seventh Edition  1409
VVentricular Premature Complexes
  BASICS
Single cardiac impulse initiated within the 
ventricles instead of the sinus node.
• QRS complexes typically wide and bizarre 
(see Figures 1 and 2). • P waves dissociated 
from the QRS complexes.
Mechanisms include increased automaticity, 
reentry, and delayed afterdepolarizations.
Cardiovascular—secondary effects on other 
systems because of poor perfusion.
GENETICS
• Polygenic in German shepherd dogs—inherited 
ventricular arrhythmia. • Likely autosomal 
recessive, possibly autosomal dominant with 
incomplete penetrance in Rhodesian ridgebacks—
inherited ventricular arrhythmia.
Unknown
Species
• Common in large-breed dogs with cardiomyo -
pathy, especially boxers (arrhythmogenic right 
ventricular cardiomyopathy) and Doberman 
pinschers. • Inherited ventricular arrhythmia in 
German shepherd dogs and Rhodesian ridge -
backs. • Common in cats with cardiomyopathy; 
occasionally seen in cats with hyperthyroidism.
Seen in all age groups.
SIGNS
• Weakness. • Exercise intolerance. • Syncope. 
• Sudden death. • Often asymptomatic.Physical Examination Findings
• Irregular rhythm associated with pulse deficits; 
may auscult splitting of the first or second heart 
sound. • May be normal if arrhythmia is 
intermittent and absent during examination. 
• May observe signs of congestive heart failure 
(CHF) (e.g., dyspnea, cough) or murmur, 
depending on the cause of arrhythmia.
CAUSES
• Cardiomyopathy. • Congenital defects 
(especially subaortic stenosis). • Degenerative 
valve disease. • Gastric dilation and volvulus. 
• T raumatic myocarditis (dogs). • Digitalis 
toxicity. • Hyperthyroidism (cats). • Cardiac 
neoplasia. • Myocarditis. • Pancreatitis.
• Hypokalemia. • Hypomagnesemia. 
• Acid–base disturbances. • Hypoxia.
  DIAGNOSIS
• Supraventricular premature beats with 
bundle branch block. • Look for P waves 
associated with the wide QRS complexes; an 
atrial premature complex with aberrant 
conduction has an associated P wave. • An 
atrial premature complex is usually followed 
by a noncompensatory pause in which the 
R-R interval of the two sinus complexes 
enclosing an atrial premature complex (APC) 
is less than the R-R interval of three 
consecutive sinus complexes. • A ventricular 
premature complex is usually followed by a 
compensatory pause in which the R-R 
interval of two sinus complexes enclosing a 
ventricular premature complex (VPC) is 
greater than or equal to the R-R interval of 
three consecutive sinus complexes.
• Hypokalemia and hypomagnesemia 
predispose animals to ventricular arrhythmias 
and blunt the response to class I antiarrhythmic drugs (e.g., lidocaine, 
procainamide, mexiletine, and quinidine). 
• High amylase and lipase if condition is 
secondary to pancreatitis.
• High T4 (cats) if condition is secondary to 
hyperthyroidism. • Increased cardiac troponin I, 
a biomarker for possible acute myocardial injury 
may suggest an underlying cardiac condition.
IMAGING
Echocardiography may reveal structural heart 
disease.
Long-term ambulatory (Holter) recording of 
the ECG to detect transient ventricular 
arrhythmias in patients with unexplained 
syncope or weakness.
  TREATMENT
Generally outpatient basis.
ACTIVITY
Restrict if the arrhythmia is accompanied by 
clinical signs or evidence of structural heart 
disease.
Alert owner to potential for the arrhythmia 
worsening and syncope or sudden death.
• Continuous ECG monitoring 
recommended while anesthetized. 
• Premedicating the patient with 
acepromazine 0.02–0.05 mg/kg raises the 
threshold for ventricular fibrillation. • Mask 
inductions not recommended; sympathetic 
release during mask induction can aggravate 
arrhythmia. • Avoid anticholinergics unless 
bradycardia develops.
Figure 1 .
VPC and a fusion complex (fifth complex) in a dog with myocarditis from pancreatitis. A fusion complex is the simultaneous activation of the ventricle by impulses 
coming from the SA node and the ventricular ectopic foci. The QRS complex is intermediate in form. (Source: From Tilley LP . Essentials of Canine and Feline 

1410  Blackwell’s Five-Minute Veterinary Consult  
V  MEDICATIONS
• Correct any hypokalemia or hypomag -
nesemia. • Drug therapy in the absence of 
clinical signs—controversial; studies in humans 
with asymptomatic VPCs and myocardial 
infarction demonstrated a high incidence of 
sudden death when treatment was initiated 
with class I antiarrhythmic agents; no similar 
studies have been conducted in veterinary 
patients. • The author generally does not 
prescribe antiarrhythmic drugs unless there is 
evidence of clinical signs of low cardiac output 
(e.g., episodic weakness or syncope) or the 
belief that the patient is at high risk of sudden 
death, based on presence of R on T 
phenomenon or breed association with VPCs 
and sudden death (e.g., boxers and Doberman 
pinschers). • If antiarrhythmic therapy is 
initiated in an attempt to lower the risk of 
sudden death, the author usually chooses a 
beta-blocker or sotalol (except in German 
shepherd dogs [see below]); no studies have 
been done to confirm efficacy of beta-blockers 
for prevention of sudden death in dogs or cats.
Dogs
• Patient not in CHF or hypotensive—initiate 
therapy with a beta-blocker such as propranolol 
0.2–1 mg/kg PO q8h, atenolol 0.2–1 mg/kg 
q12h, or metoprolol 0.2–1 mg/kg PO q8–12h or 
class III agent sotalol 1–3.5 mg/kg PO q12h. 
• Patient in CHF or hypotensive—initiate 
therapy with a class I antiarrhythmic agent such as 
mexiletine 5–8 mg/kg PO q8h or procainamide 
8–20 mg/kg PO q6–8h. • Combine a class I 
antiarrhythmic drug with a beta-blocker or sotalol 
if arrhythmia persists; especially in boxers. 
• Sotalol monotherapy may have proarrhythmic 
effect in German shepherd dogs.
Cats
Atenolol 6.25–12.5 mg PO q12h.
Avoid atropine, catecholamines (e.g., epinephrine 
and dopamine) until arrhythmia is controlled.PRECAUTIONS
• Use beta-blockers cautiously in animals with 
CHF; they initially depress myocardial contractility. 
• Use digoxin cautiously; it can potentially 
aggravate ventricular arrhythmias. • Drugs that 
prolong the action potential (e.g., sotalol) may 
worsen arrhythmia in German shepherd dogs with 
Quinidine and amiodarone raise serum 
digoxin levels.
• Consider amiodarone 5–10 mg/kg PO q12h 
for refractory arrhythmias in dogs (generally 
reserved for ventricular tachycardia); may not 
want to use in Doberman pinschers. 
• Consider sotalol 10–20 mg/cat PO q12h or 
procainamide 3–8 mg/kg PO q6–8h for cats 
that do not tolerate beta-blockers.
  FOLLOW-UP
• Holter monitoring preferred for monitoring 
severity of the arrhythmia and efficacy of 
antiarrhythmic therapy; the goal of antiarrhy -
thmic therapy is to reduce the frequency of 
ventricular ectopy by >85%. • Serial ECGs are 
not as useful as Holter monitoring—VPCs and 
paroxysmal ventricular tachycardia can occur 
sporadically through the day. • Serum digoxin 
levels in patients receiving that medication.
• Correct predisposing factors such as 
hypokalemia, hypomagnesemia, myocardial 
hypoxia, and digoxin toxicity. • Do not breed 
affected German shepherd dogs or Rhodesian 
ridgebacks with inherited ventricular arrhythmias.
Syncope, sudden death.
• If cause is metabolic—condition may 
resolve with good prognosis. • If condition is 
associated with cardiac disease—prognosis is 
guarded; VPCs may increase the risk of 
sudden death.  MISCELLANEOUS
SEE ALSO
• Chagas Disease (American T rypanoso -
miasis). • Digoxin Toxicity. • Myocarditis. 
• APC = atrial premature complex. • CHF = 
congestive heart failure. • T4 = thyroxine. 
Oyama MA, Sleeper MM, eds. Manual of 
Canine and Feline Cardiology. 5th ed. St. 
Kraus MS, Ridge LG, Gelzer ARM, et al. 
Toxicity in Doberman pinscher dogs with 
ventricular arrhythmias treated with amiodar -
one. J Vet Intern Med 2005, 19(3):407.
Meurs KM, Spier AW, Wright NA, et al. 
Comparison of the effects of four 
antiarrhythmic treatments for familial 
ventricular arrhythmias in boxers. J Am Vet 
Med Assoc 2002, 221(4):522–527.
Meurs KM, Weidman JA, Rosenthal SL, et al. 
Ventricular arrhythmias in Rhodesian 
ridgebacks with a family history of sudden 
death and results of a pedigree analysis for 
potential inheritance patterns. J Am Vet 
Med Assoc 2016, 248(10):1135–1138.
Moïse NS, Gilmour RF Jr., Riccio ML, et al. 
Diagnosis of inherited ventricular 
tachycardia in German shepherd dogs. J Am 
Vet Med Assoc 1997, 210(3):403–410.
Tilley LP , Smith FWK, Jr. Electrocardio -
graphy. In: Smith FWK, Tilley LP , Oyama 
Figure 2.
Ventricular bigeminy. Every other complex is a VPC from the same focus. Each is coupled (interval the same between it and the adjacent sinus complex) to the preceding normal 
complex. (Source: From Tilley LP . Essentials of Canine and Feline Electrocardiography, 3rd ed. Baltimore: Williams & Wilkins, 1992. Reprinted with permission of Wolters Kluwer.)Ventricular Premature Complexes  (continued)

Canine and Feline, Seventh Edition  1411
VVentricular Septal Defect
  BASICS
An anomalous communication between the 
two ventricles. Numerous classification schemes 
have been proposed; briefly, the defect may be 
in the outlet, muscular, or membranous 
septum. Most ventricular septal defects (VSDs) 
in small animals are perimembranous, such that 
the defect is subaortic and has a right 
ventricular orifice that is beneath the septal 
leaflet of the tricuspid valve.
• A VSD results in an interventricular 
communication—direction and volume of 
the shunt are determined by the size of the 
defect, the relationship of the pulmonary and 
systemic vascular resistances, and the presence 
of other anomalies.
• Most VSDs in dogs and cats are small and 
therefore restrictive (i.e., sufficiently small that 
the difference between left and right ventricu -
lar pressures is maintained). Moderate-sized 
VSDs are only partially restrictive and result in 
various degrees of right ventricular hyperten -
sion. Large VSDs have an area that is as large 
as or larger than the open aortic valve; they are 
nonrestrictive, so that left and right ventricular 
pressures are necessarily equal. Only moderate 
and large defects impose a pressure load upon 
the right ventricle (Figure 1).
• In a patient with normal resistance to right 
ventricular ejection, the direction of the shunt is left-to-right, which increases pulmonary 
venous return and imposes a volume load on 
the left atrium and ventricle. With large 
shunts, congestive failure can develop.
• Unless the defect is of moderate or large 
size, the right ventricle is spared.
• Respiratory—if pulmonary edema 
develops.
• Cardiovascular—a large shunt can result in 
pulmonary vascular disease, pulmonary 
hypertension, and shunt reversal (i.e., 
Eisenmenger’s syndrome). This is uncommon 
in small animals; if shunt reversal occurs, it 
seems to do so early in life.
GENETICS
Breed predispositions recognized; genetic 
transmission has not been established.
One of the most common congenital cardiac 
malformations in cats, comprising 50% of 
cases with congenital cardiac defects in one 
study. Less common in dogs, reported to 
occur in 7.5–14.4% of cases with congenital 
N/A
Species
English bulldog, English springer spaniel, 
basset hound, Akita, West Highland white 
terrier, Lakeland terrier.
Most defects detected during routine 
examination of puppies and kittens.
N/A
SIGNS
• Clinical signs of left ventricular failure 
include dyspnea, exercise intolerance, 
syncope, and cough.
• A restrictive VSD results in a systolic 
murmur that typically is loud, band-shaped, 
and heard best over the right hemithorax. A 
diastolic decrescendo murmur may result if 
the VSD undermines anatomic support of the 
aortic valve, causing aortic regurgitation. 
Patients with right-to-left shunts generally do 
not have murmurs.
• Split second heart sound in some patients.
• Femoral pulses usually normal.
• Mucous membranes—pink, unless 
pulmonary vascular disease causes a right-to-
left shunt and arterial hypoxemia.
• Tachycardia, dyspnea, and crackles may be 
evident if left ventricular failure occurs.CAUSES
Congenital; may have a genetic basis.
  DIAGNOSIS
• Other congenital cardiac malformations 
that cause systolic murmurs include atrio  - 
ventricular valve dysplasia, aortic or pulmo-
nary stenosis, and complex malformations 
such as tetralogy of Fallot.
• The “to-and-fro” murmur, consisting of 
distinct systolic and diastolic murmurs, which 
results when aortic valve regurgitation 
complicates a VSD must be distinguished 
from the continuous murmur of patent 
ductus arteriosus.
• Generally, diagnosis of congenital cardiac 
malformations requires echocardiographic 
evaluation including Doppler studies.
• Uncommon right-to-left shunting results in 
compensatory erythrocytosis.
• Patients with severe congestive heart failure 
(CHF) may have prerenal azotemia.
N/A
IMAGING
• Radiographic appearance is determined by 
the size and direction of the shunt. Thoracic 
radiographs may be normal if the VSD is 
small. Larger defects cause various degrees of 
left or even generalized cardiac enlargement. 
Pulmonary hyperperfusion with prominence 
of the main pulmonary artery segment may 
be apparent. CHF is manifest as pulmonary 
edema.
• Patients with right-to-left shunts have 
right-sided cardiomegaly; the pulmonary 
arteries are large proximally but distally 
attenuated, and the pulmonary veins are small 
because of reduced pulmonary perfusion.
• T wo-dimensional echocardiography may 
demonstrate left atrial enlargement with left 
ventricular dilation and hypertrophy. Systolic 
myocardial function is usually preserved. 
Right ventricular hypertrophy is apparent 
only if the defect is moderate or large in size, 
or if the VSD is one aspect of a complex 
malformation such as tetralogy of Fallot. 
Careful study usually demonstrates the defect. 
Evaluate echocardiographic images critically; 
the artifact of “septal drop-out” is very 
common.
• The diagnosis is confirmed by Doppler 
interrogation of the interventricular septum. 
If the defect is restrictive, spectral Doppler 
reveals a high-velocity systolic jet. The shunt 
may be seen directly by color-flow Doppler. RA
RV LVPTLAAo
Figure 1 .
Ventricular septal defect. In this schematic, the defect 
results in an unobstructed communication and there -
fore, right ventricular hypertrophy and pulmonary 
hypertension are shown. Left-to-right shunting is shown. 
RA = right atrium, LA = left atrium, RV = right ventricle, 
LV = left ventricle, Ao = aorta, PT = pulmonary trunk. 
(Source: Roberts W., Adult Congenital Heart Disease. 
Philadelphia, © 1987 F .A. Davis Company.)

1412  Blackwell’s Five-Minute Veterinary Consult  
VContrast echocardiography may help in the 
diagnosis of a right-to-left VSD.
• Infrequently, VSDs spontaneously close. 
The mechanism of closure is usually 
adherence of a part of the septal tricuspid 
valve leaflet to the interventricular septum 
resulting in the echocardiographic appearance 
of “septal aneurysm,” which is an incidental 
echocardiographic finding.
Selective cardiac catheterization allows 
visualization of the defect by contrast 
angiocardiography and calculation of the 
shunt fraction (QP/QS) and pulmonary 
vascular resistance.
• Evidence of left atrial enlargement, left 
ventricular hypertrophy, or even right 
ventricular hypertrophy in some animals.
• Right ventricular enlargement pattern in 
most animals that have a right-to-left shunt 
because of pulmonary vascular disease or 
pulmonic stenosis.
Size of the defect determines the degree of 
chamber enlargement and hypertrophy; 
pulmonary edema and possibly ascites are 
seen in patients with CHF .
  TREATMENT
Clinical signs are related to CHF; most 
patients can be treated as outpatients.
N/A
ACTIVITY
Restrict if animal has CHF; need not restrict 
asymptomatic patients with small defects.
DIET
Moderate sodium restriction recommended 
for patients with CHF .
Definitive surgical correction is not widely 
available; if CHF develops, it is terminal, 
even with palliative care.
• Only a minority of VSDs are sufficiently 
large to warrant repair.
• Consider definitive surgical repair of the 
defect during cardiopulmonary bypass for 
defects associated with a large shunt. 
Cardiopulmonary bypass is presently 
performed at a small number of veterinary 
centers. Consider pulmonary artery banding as a palliative procedure for patients with 
moderate or large shunts and CHF .
• Some VSDs are amenable to transcatheter 
closure using purpose-designed metallic 
occluder devices.
Furosemide, enalapril, pimobendan, and, in 
some circumstances, digoxin—recommended 
for animals with CHF (see Congestive Heart 
Failure, Left-Sided).
Vasodilators—contraindicated or used only 
with great caution in patients with complex 
ACE inhibitors and digoxin must be used 
cautiously if patient has renal dysfunction.
  FOLLOW-UP
Periodic echocardiographic or radiographic 
evaluation suggested for patients without 
Breeding affected animals is not 
• Left ventricular CHF .
• Pulmonary hypertension.
• Patients with small shunts generally have a 
normal lifespan; isolated, restrictive VSDs 
usually do not cause clinical signs.
• Concurrent anomalies such as pulmonic 
stenosis or aortic insufficiency worsen the 
• Patients with overt CHF may live 6–18 
months with medical treatment.
• The development of pulmonary hypertension 
and shunt reversal is uncommon but generally 
associated with a poor prognosis.
• VSD may be one component of complex 
malformations such as tetralogy of Fallot.• Most VSDs are perimembranous and 
therefore, subaortic. As a result, aortic valve 
insufficiency resulting from a poorly 
supported aortic valve complicates the 
condition in some patients.
• VSD may be associated with an atrial septal 
defect as part of an atrioventricular septal 
defect.
The murmur of VSD becomes apparent 
shortly after birth, when pulmonary vascular 
resistance decreases.
N/A
High risk in patients with large defects; 
breeding affected animals is not 
SYNONYMS
Interventricular septal defect.
SEE ALSO
Bomassi E, Misbach C, Tissier R, et al. 
Signalment, clinical features, 
echocardiographic findings, and outcome of 
dogs and cats with ventricular septal defects: 
109 cases (1992–2013). J Am Vet Med 
Assoc 2015, 247(8):166–175.
25(3):477–483.
Thomas WP , Shimizu M, Tanaka R, et al. 
Echocardiographic diagnosis of congenital 
membranous ventricular septal aneurysm in 
the dog and cat. J Am Anim Hosp Assoc 
2005, 41(4):215–220.
Tidholm A, Ljungvall I, Michal J, et al. 
Congenital heart defects in cats: a 
retrospective study of 162 cats (1996–2013). 
J Vet Cardiol 2015, 17:S215–S219.
available onlineVentricular Septal Defect  (continued)

Canine and Feline, Seventh Edition  1413
VVentricular Standstill (Asystole)
 BASICS
Absence of ventricular complexes on the ECG 
or absence of ventricular activity (electrical–
Ventricular asystole can result from severe 
sinoatrial block or arrest or by third-degree 
atrioventricular (AV) block without a 
junctional or ventricular escape rhythm; ECG 
features include:
• P waves present if patient has complete AV 
block (Figure 1).
• P waves absent during asystole if patient has 
severe sinoatrial block or arrest.
• No QRS complexes.
• Electrical–mechanical dissociation—a 
recorded ECG cardiac rhythm (P-QRS-T) 
and no effective cardiac output or palpable 
femoral pulse.
Ventricular asystole represents cardiac arrest; 
if the ventricular rhythm is not restored in 
3–4 minutes, irreversible brain injury can 
occur.
• All organ systems affected by loss of 
GENETICS
N/A
Unknown
None
Species
Unknown
SIGNS
• Severe systemic illness or cardiac disease in 
many patients.
• Other cardiac arrhythmias in some.
• Syncope.
• No ventricular pulse can be palpated.
• Death.
CAUSES
• Complete AV block with absence of 
ventricular or junctional escape rhythm.
• Severe sinus arrest or block.
• Hyperkalemia (Figure 2).
• Any severe systemic illness (e.g., severe 
acidosis and hyperkalemia) or heart disease.
• Hypoadrenocorticism causing hyperkalemia.
• Urinary tract rupture or obstruction, 
resulting in hyperkalemia.
 DIAGNOSIS
Rule out ECG artifact; reapply ECG clips 
and make sure skin contact is good and 
adequate alcohol is applied to leads.
Severe hyperkalemia is a possible cause.
N/A
IMAGING
N/A
Systemic blood pressure—readable pressure 
absent.
N/A TREATMENT
• Asystole is a frequently fatal rhythm 
requiring immediate aggressive treatment.
• Artificial pacing with a transvenous or 
transthoracic pacemaker may succeed if 
myocardium is mechanically responsive.
• DC electrical conversion is not 
effective unless the rhythm can first be 
converted to ventricular fibrillation with 
T reat any treatable problems such as 
hypothermia, hyperkalemia, and acid–base 
ACTIVITY
N/A
DIET
N/A
None
None
• Institute cardiopulmonary resuscitation.
• Epinephrine 0.2 mg/kg IV, intratracheal 
(IT), or intralingual (IL) (double the dose for 
IT administration and deliver with equal 
volume of saline).
• Atropine 0.05 mg/kg IV, IT, or IL (double 
the dose for IT administration and deliver 
with equal volume of saline).
• Sodium bicarbonate 1 mEq/kg IV for each 
10 minutes of cardiac arrest.
• Dexamethasone and dopamine may be 
helpful in patients with electrical–mechanical 
dissociation.
Figure 1 .
Ventricular asystole in a dog with severe complete AV block. Only P waves (atrial activity) are present; there is no ventricular activity. Lead II, 50 mm/s, 1 cm = 1 mV. (Source: 

1414  Blackwell’s Five-Minute Veterinary Consult  
VVentricular Standstill (Asystole)  (continued) 
Drugs that depress sinus node or AV node 
conduction in patients with sinus arrest or 
heart block (e.g., beta-blockers, calcium 
channel blockers, digoxin).
None
None
Calcium gluconate—patients with ventricular 
standstill and hyperkalemia.
 FOLLOW-UP
• If animal is resuscitated—evaluate CBC, 
biochemical analysis, and urinalysis.
• If animal survives and primary cardiac 
disease is suspected—echocardiogram and 
• ECG—closely and frequently.
prevent and correct acid–base and electrolyte 
disturbances, hypotension, and hypoxemia.POSSIBLE COMPLICATIONS
• Death.
(DIC) and multiorgan failure.
Usually death. If sinus rhythm reestablished, 
prognosis still usually guarded to poor as not 
uncommon to arrest again.
None
None
None
None
SYNONYMS
Ventricular asystole.
SEE ALSO
• Atrioventricular Block, Complete (Third Degree).
• Cardiopulmonary Arrest.
• Sinus Arrest and Sinoatrial Block.ABBREVIATIONS
• IL = intralingual.
• IT = intratracheal.
conduction disturbances. In: Smith, FWK, 
2016.
LP , Oyama MA, Sleeper MM, eds. Manual 
of Canine and Feline Cardiology, 5th ed. 
St. Louis, MO: Saunders Elsevier, 2016.
Figure 2.
Ventricular asystole in a cat with severe hyperkalemia (11 mEq/L) from urethral obstruction. No P waves or QRS complexes are seen after four wide and bizarre 
QRS complexes (atrial standstill with delayed ventricular conduction). Lead II, 50 mm/s, 1 cm = 1 mV.) (Source: From Tilley LP . Essentials of Canine and Feline 

Canine and Feline, Seventh Edition  1415
VVentricular Tachycardia
  BASICS
Ventricular tachycardia (VT) may occur in 
structurally normal hearts (hereditary 
arrhythmias) or may be a manifestation of 
myocardial abnormalities associated with 
cardiomyopathy, significant valvular disease, 
myocarditis, infiltrative disease or electrolyte 
abnormalities. To date, no available medical 
therapy is known to prevent sudden death 
(SD) in animals afflicted with VT.
Severity of VT depends both on the 
hemodynamic consequences (hypotension) 
and on the electrical instability of a rhythm, 
i.e. its potential to degenerate into ventricular 
fibrillation (VF), resulting in SD. In 
Dobermans, SD due to VT–VF occurs in 
about 30–50% of cases. In boxers with 
arrhythmogenic right ventricular cardio­
myopathy (ARVC), 33% are syncopal due to 
VT and 30% have SD due VT–VF . Similarly, 
13% of English bulldogs with inherited 
ARVC experience SD. Underlying mechanisms 
of VT include increased auto  maticity, reentry, 
and triggered activity.
ECG Features (Figure 1)
• QRS complexes—typically wide and 
bizarre.
• Three or more ventricular premature 
contractions in a row.
• May be intermittent (paroxysmal) or 
sustained; heart rate usually >150 bpm with a 
regular or irregular rhythm.
• P waves, if visible, are dissociated from the 
• Breed ­specific ECG changes—VT in boxers 
is characteristically positive in the ventrocaudal 
leads (leads II, III, and aVF), thus manifests a 
“left bundle branch block pattern.” VT in 
Doberman pinschers and German shepherd 
dogs has both polymorphic and 
monomorphic characteristics.
Cardiovascular system, with secondary effects 
on other systems due to poor perfusion.
GENETICS
• In boxers, ARVC is inherited as autosomal 
dominant trait with adult onset of disease. 
Some boxers have a mutation in the striatin 
gene, but the disease is manifested with 
incomplete penetrance (i.e., even if a boxer has 
the genetic mutation, it may not lead to the 
development of arrhythmias in that dog) and it 
is likely that there is more than one mutation 
in boxers that may lead to the disease in some 
lines. Striatin is a desmosomal protein 
(scaffolding protein) located in the intercalated 
disc region of the cardiomyocyte and 
colocalizes with desmosomal proteins such as 
plakophilin ­2 and other known proteins that are mutated in human ARVC. DNA test 
results can indicate if a dog is heterozygous or 
homozygous for the genetic striatin deletion. 
Homozygous dogs are more likely to show 
disease and should not be used for breeding.
• English bulldogs also appear to harbor a 
form of inherited ARVC manifest with VT 
and SD in 13% of dogs. Genetic mode of 
inheritance is undetermined. There is 2.9:1 
male to female ratio of affectedness. Unlike 
boxers with ARVC, the majority of English 
bulldogs appear to present with signs of CHF 
at the time of arrhythmia detection.
• Dilated cardiomyopathy with VT in 
Doberman pinschers is inherited as an auto  ­ 
somal dominant trait with adult onset of 
disease. In Dobermans there are two genetic 
mutations associated with dilated cardiomyo­
pathy (DCM) and VT identified in the 
pyruvate dehydrogenase kinase 4 (PDK4) 
gene ( PDK4/NCSU/DCM1 ) and the titin 
gene ( NCSU DCM2 ). Dogs with both 
mutations are at the highest risk of getting 
DCM, although dogs with a mutation in 
either gene can develop the disease as well.
• Inherited VT and SD, considered primarily 
an “electrical disorder” (since no underlying 
structural heart disease is identified), is found 
in young German shepherd dogs and English 
springer spaniels. They have been shown to 
have inherited channelopathies, resulting in 
repolarization abnormalities. In springer 
spaniels a mutation in the KCNQ1  gene, 
responsible for a repolarizing K channel, was 
found to exhibit QT interval prolongation on 
ECG and SD. In German shepherd dogs, the 
mode of inheritance is polygenic due to an 
abnormality in a major gene with modifiers.
• Young Rhodesian ridgebacks have been 
found to be affected with severe ventricular 
arrhythmias and SD. It is inherited in an 
autosomal recessive mode and linked to a 
genetic mutation, likely associated with 
mitochondrial alterations.
Common in dogs; uncommon in cats.
None
Species
Commonly seen in large ­breed dogs with 
cardiomyopathy, especially boxers and 
Doberman pinschers, also in German 
shepherd dogs and Rhodesian ridgebacks.
• All age groups, if not breed ­specific VT.
• Boxers with ARVC usually present at 4–6 
years of age; frequency and severity of the 
arrhythmia usually increase over time.
• Doberman pinschers with occult cardio­
myopathy typically develop ventricular arrhythmias beginning at 3–6 years of age, but 
it also can occur much later in life; frequency 
and severity usually increase over time.
• German shepherd dogs develop ventricular 
arrhythmias at 12–16 weeks of age and the 
frequency and severity of the arrhythmias 
increase until 24–30 weeks of age. After 8 
months of age the arrhythmia severity 
stabilizes or starts to decrease.
• The Rhodesian ridgeback’s most severe 
arrhythmias are found between 6 and 30 
months of age, after which many dogs appear 
to outgrow the problem.
• Bulldogs with ARVC have a mean age of 9.2 
years at time of presentation for arrhythmias.
SIGNS
• Syncope.
• SD.
• May be normal if arrhythmia is paroxysmal 
and absent during examination.
• Paroxysmal or sustained tachycardia may be 
ausculted.
• Femoral pulses may have variable pulse 
intensity or be weak during runs of VT.
• Signs of CHF or a murmur may be present, 
depending on cause of arrhythmia.
CAUSES
• Inherited channelopathies.
• Congenital defects (especially subaortic 
stenosis).
• Chronic degenerative valve disease.
• T raumatic or infectious myocarditis.
• Gastric dilation and volvulus.
• Splenic neoplasia/hemorrhage.
• Hyperthyroidism (cats).
• Digitalis toxicity.
• VT can also be found in dogs affected with 
noncardiac disease states including electrolyte 
abnormalities (potassium), or systemic diseases 
where imbalance of cardiac autonomic 
modulation may elicit VT. The VT occurring 
secondary to those circumstances may occur at 
heart rates similar to the sinus rate (in this 
scenario the rhythm is termed “accelerated 
idioventricular rhythm” rather than VT since 
the heart rate is normal), thus considered less 
malignant, and are often self ­limiting with 
correction or resolution of the underlying cause.
• Hypokalemia, hyperkalemia.
• Neoplasia (e.g., cardiac or splenic 
hemangiosarcoma).
• Anemia.

1416  Blackwell’s Five-Minute Veterinary Consult  
V  DIAGNOSIS
Supraventricular tachycardia with bundle 
branch block. If P waves can be identified, 
look for association between P waves and 
QRS complexes. If there is a consistent PR 
interval, then the rhythm is supraventricular 
with bundle branch block. If there is no 
association between P waves and QRS 
complexes, the rhythm is probably VT. If P 
waves cannot be identified due to a fast rate 
(P buried in preceding T wave), lidocaine 
administration may result in slowing of the 
VT rate and P waves may be identified if 
present. Termination of a tachyarrhythmia 
after administration of lidocaine supports 
diagnosis of VT. If no effect with lidocaine, 
esmolol administration may result in slowing 
of a supraventricular tachycardia with bundle 
branch block, so that P waves associated with 
QRS complexes can be identified.
predispose to VT and blunt response to class I 
antiarrhythmic drugs (e.g., lidocaine, 
procainamide, mexiletine, and quinidine).
• High amylase and lipase if arrhythmia is 
secondary to pancreatitis.• Inflammatory changes may occur on CBC 
such as increased neutrophil count if 
arrhythmia secondary to myocarditis.
• Increased cardiac troponin I (cTnI) with 
• High T4 (cats) if arrhythmia is secondary to 
• Lyme or tick titers in myocarditis.
• Genetic testing is available at NC State 
(https://cvm.ncsu.edu/genetics/) for 
arrhythmias originating due to boxer ARVC, 
Doberman DCM and Rhodesian ridgeback 
inherited arrhythmias.
• Increased trypsin ­like immunoreactivity 
and pancreatic lipase immunoreactivity if 
suspect pancreatitis is a cause for the VT.
IMAGING
Echocardiography may reveal underlying 
ECG and long ­term ambulatory (Holter) or 
event recording of the ECG—for detection of 
intermittent VT in patients with unexplained 
Vary with underlying cause.  TREATMENT
• Most patients with intermittent VT can 
safely be evaluated for underlying diseases 
(echocardiogram, lab work) and it is ideal to 
establish a true baseline of the arrhythmia 
quantity and quality by a 24 ­hour Holter 
prior to initiating therapy.
• If unstable (laterally recumbent, weak, or 
frequent syncope), immediate IV treatment in 
a hospital setting with continuous ECG 
monitoring may be required. Once the 
arrhythmia is controlled and patient is 
hemodynamically stable, oral medication 
should be instituted. A follow ­up 24 ­hour 
Holter is required to evaluate efficacy and 
possible pro ­arrhythmic effects of 
antiarrhythmic therapy.
ACTIVITY
Boxers tend to have an increased incidence of 
VT during excitement, so in some cases 
owners should know what specific situations 
to avoid. In humans with ARVC, exercise has 
been shown to exacerbate arrhythmia 
incidence and risk of SD.
Figure 1 .
Ventricular tachycardia. 6 ­lead ECG demonstrating the wide and bizarre QRS complexes that occur 
in runs of up to 6 beats in a Doberman pinscher with DCM. Ventricular tachycardia should be 
treated as soon as possible. Acid–base and electrolyte abnormalities should always be corrected.Ventricular Tachycardia  (continued)

Canine and Feline, Seventh Edition  1417
VDIET
Dogs with diet ­associated (boutique, exotic ­ 
ingredient, or grain ­free [BEG] diets) DCM 
may have an increased incidence of VT and 
risk of SD.
Alert the owner to the potential for SD.
• When possible, determine the cause of the 
arrhythmia and treat it prior to inducing 
general anesthesia.
• Assess if VT is correctable with a test dose 
of lidocaine; if it is, treat as necessary with 
lidocaine, either using IV boluses or CRI.
• Premedication with acepromazine 
0.02–0.05 mg/kg raises the threshold for VF .
• Avoid proarrhythmic drugs such as alpha ­2 
agonists (xylazine, medetomidine) and 
thiopental.
• Mask induction is not recommended in 
inadequately sedated patients with ventricular 
arrhythmias because increased sympathetic 
tone during mask induction will aggravate the 
• Continuous ECG monitoring during 
Correct any hypokalemia or hypomagne­
semia, if possible, prior to instituting medical 
therapy.
Dogs
Acute Life-Threatening VT
• Administer lidocaine slowly in 2 mg/kg IV 
boluses (up to 8 mg/kg total) to convert to 
sinus rhythm; follow with lidocaine CRI, 
30–80  μg/kg/min.
• If lidocaine fails—administer procainamide 
5–15 mg/kg slow IV bolus (may cause 
vomiting or hypotension due to negative 
inotropic effect), followed by 25–50  μg/kg/
min IV CRI.
• In cases of refractory VT, lidocaine and 
procainamide CRIs can be combined.
• If no response to lidocaine or procainamide, 
amiodarone (Nexterone®) can be administered 
as a 2 mg/kg IV bolus infused over 10 
minutes, followed by a CRI of 0.8 mg/kg/h 
for 6 hours, then decrease to 0.4 mg/kg/h or 
alternatively try slow IV boluses of esmolol (a 
short ­acting beta ­blocker) at 0.05–0.1 mg/kg 
q5min to a cumulative dose of 0.5 mg/kg, or 
as a 50–200  μg/kg/min CRI.
• If there is inadequate response to the 
various IV therapies, then PO medication 
may be administered. Sotalol 1.5–2.5 mg/kg 
PO q12h may convert dangerous VT within 
1–3 hours in such situations, even when the 
usual IV medications failed. It can be 
administered in a “loading protocol” (1.5–2.5 mg/kg PO q4h or q6h), for the first 
2 doses, depending on the severity of the VT 
and myocardial function.
Chronic VT in a Stable Patient
• Sotalol 1–2.5 mg/kg PO q12h.
• Mexiletine monotherapy is not very 
effective, but combination of mexiletine 
4–8 mg/kg PO q8h with a beta ­blocker such 
as atenolol 0.25–1 mg/kg PO q12h or sotalol 
1–2.5 mg/kg PO q12h may be more effective 
for refractory VT, especially in boxers.
• Amiodarone may be used for refractory VT 
in dogs with poor myocardial function 
(loading dosage of 5–15 mg/kg PO q12h for 
2–14 days, maintenance dosage of 6–15 mg/
kg PO q24h). Requires regular monitoring 
due to the risk for serious side effects in dogs 
(hepatotoxicity, neutropenia, thyroid 
dysfunction). Signs of toxicity include 
anorexia, vomiting, lethargy, and hepatic 
enzyme elevation. Amiodarone hepatopathy is 
reversible after reduction of dosage or 
discontinuation of the drug. Overt clinical 
signs of toxicity generally resolve within a few 
days of stopping amiodarone. Monitoring of 
serial serum chemistries is recommended, 
since increases in liver enzyme activities 
usually precede the onset of clinical signs of 
amiodarone toxicity. Liver enzymes should be 
measured after 7 days of drug loading and 
once monthly during maintenance therapy.
• Amiodarone can be combined with atenolol 
0.5–1.0 mg/kg twice a day to enhance anti  ­ 
arrhythmic effects.
• In German shepherd dogs the combination 
of mexiletine and sotalol is the most effective 
therapy for VT. Sotalol monotherapy should 
be avoided due its proarrhythmic effects in 
Cats
• Use lidocaine cautiously and only for 
sustained VT; neurotoxicity (seizures) is 
common in cats. Use one ­tenth of the dosage 
used for dogs.
• For oral maintenance therapy of severe VT 
in cats use sotalol 10 mg/cat q12h or atenolol 
6.25–12.5 mg PO q12h.
Avoid atropine, catecholamines (e.g., 
epinephrine, dopamine) until arrhythmia is 
• Use beta ­blockers cautiously in animals 
with CHF . Monitoring by echocardiogram is 
recommended to check for worsening of 
myocardial function due to beta blockade.
• Sotalol, when used as a sole agent, and other 
drugs that prolong action potential duration 
may worsen VT in German shepherd dogs 
with inherited ventricular arrhythmias.
Quinidine and amiodarone raise digoxin 
levels.  FOLLOW-UP
• Holter monitoring is preferred for assess­
ment of severity of the arrhythmia and 
efficacy of antiarrhythmic therapy; the goal 
of antiarrhythmic therapy is to reduce the 
frequency of ventricular ectopy by >85%.
• Serial ECG and telemetry can be used 
alternatively—but not as meaningful as Holter 
monitoring because ventricular premature 
complexes and paroxysmal VT can occur 
sporadically throughout the day.
hypoxia, and digoxin toxicity.
• In boxers, limit significant stress or 
excitement as the increase in sympathetic tone 
may exacerbate the arrhythmia.
• Syncope.
• SD.
resolve with a good prognosis.
• If condition is associated with cardiac 
disease—prognosis is guarded because the 
underlying heart disease is likely chronic and 
progressive and therefore the arrhythmias may 
also worsen over time; presence of significant 
VT increases the risk of SD.
• If VT associated with hemangiosarcoma 
(cardiac or splenic)—the long ­term outcome 
is grave due to the poor prognosis of the 
• Approximately 50% of German shepherd 
dogs with more than 10 runs of VT/24 hours 
die suddenly.
• Doberman pinschers with VT and DCM may 
die suddenly during their first syncopal episode.
N/A
If German shepherd dogs reach the age of 
18 months, the probability of SD decreases, 
similarly in Rhodesian ridgebacks, after 
30 months of age.
None
N/A
SEE ALSO
Ventricular.(continued)  Ventricular Tachycardia

1418  Blackwell’s Five-Minute Veterinary Consult  
V• Cardiomyopathy, Dilated—Dogs.
• Chagas Disease (American 
T rypanosomiasis).
• Ventricular Arrhythmias and Sudden Death 
in German Shepherds.
• ARVC = arrhythmogenic right ventricular 
cardiomyopathy.• CHF = congestive heart failure.
• cTnI = cardiac troponin I.
• DCM = dilated cardiomyopathy.
• PDK4 = pyruvate dehydrogenase kinase 4.
• SD = sudden death.
Cunningham SM, Sweeney JT, MacGregor J, 
et al. Clinical features of English bulldogs with presumed arrhythmogenic right 
ventricular cardiomyopathy: 31 cases 
(2001–2013). J Am Anim Hosp Assoc 
2018, 54(2):95–102.
Authors  Marc S. Kraus and Anna R.M. 
Gelzer
available onlineVentricular Tachycardia  (continued)

Canine and Feline, Seventh Edition  1419
VVertebral Column Trauma
  BASICS
• Vertebral column trauma are caused by the 
application of exogenous forces to the vertebrae, 
intervertebral discs, tendons, ligamentous 
support structures, and the spinal cord.
• The clinical signs may include spinal 
hyperesthesia, limb paresis and/or proprio­
ceptive ataxia, para ­ or tetraplegia, loss of 
nociception, urinary retention, and fecal 
• In the normal vertebral column, passive 
(bones, ligaments, discs), active (tendons, 
muscles), and neural systems are responsible 
for stability.
• Compression, lateral bending, torsion, and 
sheer forces may result in failure of these 
systems, leading to vertebral fracture or 
• In some instances, significant spinal cord 
injury (SCI) such as traumatic disc herniation, 
penetrating injuries and post ­traumatic 
vascular myelopathy, can be present without 
instability or fracture.
• SCI is the result of primary and secondary 
injuries.
• Primary injury results from initial 
mechanical events (spinal cord compression, 
contusion). The secondary injury is the 
biochemical cascade (combination of 
oxidative stress, inflammation, vascular 
injury) that follows and causes extension of 
the primary injury.
• Nervous.
• Others possible due to exogenous trauma.
• Vertebral fractures and luxations 
represented 6% of all feline myelopathies and 
7% of all canine neurology cases in two 
studies.
• The incidence of traumatic SCI without 
fracture/luxation is unknown.
Medium ­ and large ­breed dogs are more 
Most affected dogs and cats are young 
(median 2 years of age; range 0.25–15 years 
in one study).
Males appear overrepresented.
SIGNS
• The majority of dogs with vertebral column 
trauma have SCI.• Concurrent peripheral (e.g., brachial plexus 
trauma) or CNS injuries (e.g., head trauma) 
can occur.
• Abnormalities associated with other body 
systems are frequently identified.
• Acute ­onset paresis and ataxia or para ­/
tetraplegia.
• Clinical signs suggestive of hyperesthesia 
(vocalization, reluctance to move, arched 
back).
Neurologic Examination Abnormalities
• Focal SCI (affecting C1–C5, C6–T2, T3–
L3, or L4–S3 spinal cord segments) is most 
common.
• Gait abnormalities—in >90% of animals; 
may include proprioceptive ataxia, paresis, 
and loss of voluntary movement.
• Abnormalities in spinal reflexes and 
postural reactions are common and usually 
reflect the spinal cord segment(s) injured.
• Decreased spinal reflexes can also be 
secondary to spinal shock (acute, transient, 
loss of spinal reflexes, commonly withdrawal 
reflexes, after SCI).
• Regional hyperesthesia.
• Animals with severe SCI may have absent 
nociception.
• Absence of deep nociception is a negative 
prognostic indicator, with the proportion of 
animals ambulating following thoracolumbar 
vertebral fracture/luxation considered <5%.
Physical Examination Abnormalities
• Pulmonary contusions and rib fractures.
• Pelvic and appendicular bone fractures.
• Cutaneous wounds.
• T raumatic brain injury.
• Abdominal organ injury.
CAUSES
• Automobile accident is the most common 
cause of vertebral column trauma.
• Other etiologies include fall, animal bites, 
and gunshot wounds.
Animals housed outdoors, walked off lead, or 
unsecured in the cabs of pickup trucks are 
likely overrepresented.
  DIAGNOSIS
• Other neurologic diseases such as acute disc 
herniation, fibrocartilagenous embolic 
myelopathy, acute noncompressive nucleus 
pulposus extrusion, meningomyelitis, 
discospondylitis, and neoplasia, should be 
• Orthopedic injuries such as appendicular 
fracture or ligamentous injuries may 
occasionally be mistaken for vertebral column 
trauma.CBC/BIOCHEMISTRY/URINALYSIS
• Abnormalities may be present if significant 
injury has occurred to other body systems.
• Anemia, findings consistent with dehyd­
ration, elevated creatinine kinase, and 
hematuria are all commonly seen.
IMAGING
• 70% sensitive and highly specific for 
detecting vertebral fracture/luxation.
• Do not permit visualization of the spinal 
cord and have poor soft tissue detail.
Can define extradural spinal cord compres­
sion but invasive and does not allow direct 
visualization of spinal cord parenchyma; may 
not detect lateralized spinal cord compression 
and lacks the tissue detail of advanced 
imaging studies.
• CT—gold standard for evaluating the 
bones of the vertebral column and for 
visualizing mineralized disc material and 
extradural hemorrhage.
• MRI—can allow visualization of the bony 
vertebral column, but provides more soft 
tissue details than CT; it is the only means to 
exclude certain differential diagnoses, such as 
fibrocartilaginous embolism, and can provide 
prognostic information concerning recovery.
• CSF—often unremarkable or not etiology ­
specific; in some severe cases, CSF total 
protein, nucleated count, and red blood cell 
count may be increased.
• CSF is collected as an adjunct and not as a 
substitute to advanced imaging.
• Caution should be taken with CSF 
collection as positioning for cisternal or 
lumbar tap can exacerbate spinal cord injury 
by destabilizing a vertebral fracture or 
luxation.
• Gross findings may include evidence of 
vertebral luxation/fracture, extradural 
hemorrhage, disc extrusion, spinal cord 
swelling, dural/subarachnoid erythema/
hemorrhage, and myelomalacia.
• Histopathologic abnormalities within the 
spinal cord may include necrosis, demyelination, 
infarction, parenchymal hemorrhage.
  TREATMENT
• Emergency intensive care management is 
recommended for all animals immediately 
following injury.
• Surgical management is needed if imaging 
suggests significant spinal cord compression 
and/or vertebral column instability.

1420  Blackwell’s Five-Minute Veterinary Consult  
V• Medical management may be selected for 
animals that lack evidence of instability/
• Prior to imaging, animals should be 
immobilized on a back board. Animals with 
suspected cervical lesions should ideally be 
placed in a neck brace that does not impair 
their breathing.
• Animals with imaging that suggests 
vertebral column instability should be 
immobilized until surgical stabilization.
• Non­ambulatory dogs require padded 
bedding, frequent turning, and urinary 
bladder evacuation.
• Fluid therapy is required in the event of 
dehydration and to maintain adequate blood 
pressure and perfusion to the spinal cord.
• Pain management is also required.
• Sedation can be considered to avoid 
exacerbation of the signs in anxious and 
frantic animals.
• Physical rehabilitation consisting of range 
of motion exercises, active weight bearing, 
and underwater treadmill may be beneficial 
but significant mobilization should only be 
performed after any vertebral column 
instability is addressed.
ACTIVITY
• Strict exercise restriction for 4 weeks for all 
animals following vertebral column surgery. 
Animals with fractures and instability may 
require 6–8 weeks of rest.
• Medically managed animals lacking 
vertebral column instability/fracture may 
require shorter periods of rest.
• Surgery is recommended for animals with 
advanced imaging that supports significant 
spinal cord compression or vertebral column 
instability (e.g., subluxation, violation of 
multiple vertebral unit compartments).
• Spinal stapling, pins, and methylmethacrylate, 
and various plates can be used to stabilize the 
• Decompression may be needed with or 
without stabilization in cases with significant 
extradural hemorrhage or disc material.
• Rapid surgical intervention (within 48 hours) 
is usually recommended to relieve spinal cord 
compression and limit permanent damage.
• Opioid analgesics—commonly used for 
pain management; fentanyl 2–5  μg/kg CRI, 
hydromorphone 0.05–0.1 mg/kg IV q6h).• NSAIDs provide analgesia and anti ­
inflammatory effects and may be beneficial if 
hydration status, kidney, and liver functions 
are normal. Carprofen 2.2 mg/kg PO q12h 
• Gabapentin 10 mg/kg q8–12h can be 
beneficial for neuropathic pain.
• Alpha receptor antagonists can relax the 
internal urethral sphincter and facilitate 
urinary voiding in upper and lower motor 
neuron bladder dysfunction. Prazosin 
Glucocorticoids—methylprednisone sodium 
succinate (MPSS) and other glucocorticoids 
have not been shown to be beneficial in dogs 
with SCI.
• NSAIDs may result in gastric ulcers and 
• Glucocorticoids may cause gastric or 
colonic ulceration, vomiting, and urinary 
tract infections (especially dexamethasone).
• Alpha ­antagonists may result in hypo­
tension and gastrointestinal signs.
Glucocorticoids and NSAIDs should not be 
combined as this increases the risk of gastro­
intestinal adverse effects.
N/A
  FOLLOW-UP
Daily physical and neurologic examination is 
strongly suggested to monitor progression.
N/A
• Chronic ataxia/paresis as well as failure to 
regain voluntary ambulation are possible.
• Some animals may have urinary/fecal 
incontinence, especially if they are non ­ 
ambulatory.
• Non­ambulatory animals are at risk for skin 
ulcers and urinary tract infection.
• Animals with intact nociception have a 
good prognosis for ambulatory recovery if 
appropriate treatment is undertaken.
• Animals with absent nociception that have 
vertebral fracture or luxation have a very 
poor prognosis for regaining voluntary 
ambulation (<5%).  MISCELLANEOUS
Animals that have traumatic SCI often have 
injury to other body systems.
Younger animals are more commonly 
affected.
SCI may affect ability to achieve pregnancy 
and carry fetuses to term.
SYNONYMS
T raumatic myelopathy.
SEE ALSO
• MPSS = methylprednisone sodium 
succinate.
drug.
• SCI = spinal cord injury.
Bali MS, Lang J, Jaggy A, et al. Comparative 
study of vertebral fractures and luxations in 
dogs and cats. Vet Comp Orthop T raumatol 
2009, 22:47–53.
Bruce CW, Brisson BA, Gyselinck K. Spinal 
fracture and luxation in dogs and cats. Vet 
21:280–284.
Jeffery ND, Levine JM, Olby NJ, et al. 
consequences, diagnosis, treatment, and 
27:1318–1333.
Levine GJ, Levine JM, Budke CM, et al. 
Description and repeatability of a newly 
validated spinal cord injury scale for dogs. 
Prev Vet Med 2009, 89:121–127.
Jonathan M. Levine.Vertebral Column Trauma  (continued)

Canine and Feline, Seventh Edition  1421
VVesicourachal Diverticula
  BASICS
OVERVIEW
• A common congenital anomaly of the 
urinary bladder that occurs when a portion of 
the urachus (i.e., a fetal conduit that allows 
passage of urine from the bladder to the 
placenta) located at the bladder vertex fails to 
close; the result is a blind diverticulum of 
variable size that protrudes from the bladder 
vertex.
• Other characteristics include congenital 
microscopic diverticula (microscopic lumens 
that may persist at the bladder vertex).
• Acquired macroscopic diverticula develop 
after the onset of concurrent but unrelated 
acquired lower urinary tract diseases; 
presumably, urethral obstruction or detrusor 
hyperactivity induced by inflammation causes 
high intraluminal pressure and subsequent 
enlargement of microscopic diverticula.
• Congenital macroscopic diverticula, most 
likely caused by impaired urine outflow, 
develop before or soon after birth and persist 
indefinitely.
• Frequently encountered in cats with 
acquired lower urinary tract diseases; twice as 
common in male cats as in female cats.
• No breed or age predisposition.
SIGNS
Depend on concomitant disorders predispos-
ing to formation of macroscopic vesicourachal 
• Persistent congenital microscopic 
diverticula—cause unknown.
• Congenital microscopic diverticula—risk 
factors for acquired macroscopic diverticula.
• Diseases associated with increased bladder 
intraluminal pressure (e.g., bacterial urinary 
tract infection, uroliths, urethral plugs, and 
idiopathic disease)—risk factors for acquired 
macroscopic diverticula.
  DIAGNOSIS
• Persistent (or patent) urachus; rare—
characterized by inappropriate loss of urine 
through the umbilicus.
• Persistent urachal ligaments are nonpatent 
fibrous remnants of the urachus, connecting 
the bladder vertex to the umbilicus.
• Urachal cysts are focal accumulations of 
fluid in isolated segments of the urachus. 
They may be aseptic or septic.CBC/BIOCHEMISTRY/URINALYSIS
• Abnormal findings are related to the 
underlying disorder that causes vesicourachal 
diverticula, unless complicated by concurrent 
acquired lower urinary tract diseases.
• Abnormal findings related to secondary 
IMAGING
• Congenital and acquired macroscopic 
diverticula—best identified by positive-
contrast urethrocystography.
• Radiographs obtained with the bladder 
completely then partially distended with 
contrast medium may facilitate detection of 
small diverticula.
N/A
• Extramural macroscopic diverticula appear 
as convex or conical luminal projections from 
the bladder vertex.
• Intramural microscopic diverticula appear 
as transitional epithelium-lined lumens 
persisting at the bladder vertex from the level 
of the submucosa to subserosa.
  TREATMENT
• Many macroscopic diverticula in cats (and 
probably dogs) are acquired and self-limiting 
if the underlying disease is eliminated.
• Direct treatment efforts toward eliminating 
underlying cause(s) of lower urinary tract 
disease.
• Consider diverticulectomy if a macroscopic 
diverticulum persists in a patient with 
persistent or recurrent bacterial urinary tract 
infection despite appropriate antimicrobial 
therapy.
N/A
  FOLLOW-UP
If bacterial urinary tract infection persists or 
recurs despite proper antimicrobial therapy, 
the status of the diverticulum should be 
reevaluated by contrast radiography.
Avoid diagnostic procedures or treatments 
that alter normal host urinary tract defenses 
and predispose to urinary tract infection.POSSIBLE COMPLICATIONS
Persistent congenital macroscopic diverticula 
are risk factors for recurrent bacterial urinary 
• Congenital microscopic diverticula are 
usually clinically silent unless complicated by 
concurrent lower urinary tract disease.
• Acquired macroscopic diverticula typically 
heal in 2–3 weeks after amelioration of 
clinical signs of lower urinary tract disease.
• Diverticulectomy and appropriate 
antimicrobial therapy usually associated with 
resolution of recurrent urinary tract infections 
in patients with persistent congenital 
 ASSOCIATED CONDITIONS
• Persistent congenital macroscopic 
diverticula are potential risk factors for 
recurrent bacterial urinary tract infections.
• Acquired macroscopic diverticula are 
typically encountered in patients with 
concurrent lower urinary tract diseases.
SEE ALSO
Osborne CA, Johnston GR, Kruger JM, et al. 
Etiopathogenesis and biological behavior of 
feline vesicourachal diverticula. Vet Clin 
North Am Small Anim Pract 1987, 
17:697–733.

1422  Blackwell’s Five-Minute Veterinary Consult  
VVestibular Disease, Geriatric—Dogs
 BASICS
Acute-onset nonprogressive disturbance of the 
peripheral vestibular system in older dogs.
• Unknown.
• Suspected abnormal flow of the endolym-
phatic fluid in the semicircular canals of the 
inner ear secondary to disturbance in 
production, circulation, or absorption of the 
fluid.
• Possible intoxication of the vestibular 
receptors or inflammation of the vestibular 
portion of the vestibulocochlear nerve (cranial 
nerve VIII).
• Often incorrectly referred to as a stroke, 
geriatric vestibular disease is neither central in 
location nor suspected to be vascular or 
ischemic in origin.
Nervous—peripheral vestibular system.
GENETICS
N/A
Common, sporadic, acquired disease of older 
dogs.
Species
Dog
• None reported.
• Seems to occur more frequently in medium 
to large breeds.
Geriatric; patients usually >8 years old.
N/A
SIGNS
• Signs of acute onset peripheral vestibular 
dysfunction usually unilateral but occasion-
ally bilateral.
• If vestibular signs are severe, do not 
incorrectly attribute the signs (especially the 
gait) to a central (i.e., CNS) location.
• Sudden onset of imbalance, disorientation, 
reluctance to stand, and (usually) head tilt 
and irregular eye movements.
• May be preceded or accompanied by nausea 
• Head tilt—mild to marked; directed toward 
the side of the lesion; occasionally disease is 
bilateral with erratic side-to-side head 
movements either without a head tilt or with a mild tilt in direction of the more severely 
• Abnormal (resting) nystagmus common in 
early stages; either horizontal or rotatory with 
the fast phase always in the direction opposite 
to the head tilt; with bilateral disease, abnormal 
nystagmus usually mild or not present and 
physiologic nystagmus or conjugate eye 
movements diminished to absent.
• Mild to marked disorientation and 
vestibular ataxia with tendency to lean or fall 
in the direction of the head tilt.
• Strength and proprioception normal; with 
severe disease, patient may be reluctant/
unable to stand and may have other issues 
(e.g., hip dysplasia), making assessment of 
gait difficult; with bilateral disease, may have 
base-wide stance.
CAUSES
Unknown
 DIAGNOSIS
• Primarily distinguished from other causes 
of vestibular deficits by the acute onset and 
usually rapid improvement without specific 
• Otitis media and interna—may have 
concurrent ipsilateral facial nerve (cranial 
nerve VII) paresis or paralysis, deafness, and/
or Horner’s syndrome; otitis externa with 
ruptured tympanic membrane may be present 
with otitis media and interna.
• Ototoxic drugs—eliminated by history.
• T rauma—may cause similar acute changes; 
differentiated by history, results of physical 
• Hypothyroid neuropathy—usually not as 
acute in onset or as severe; may be associated 
with clinical signs of hypothyroidism and 
possible cranial nerve VII deficit. 
• Neoplasia—either affecting CN VIII 
peripherally or in a central location; signs 
usually not as acute in onset as geriatric 
vestibular disease and signs persistent and 
usually progressive in nature.
• Generally normal.
• Hemoconcentration secondary to dehydra-
tion may be present.
• Unrelated concurrent disorders (e.g., 
renal and hepatic disease) associated with 
geriatric state may cause laboratory 
N/A
IMAGING
• Usually none required.
• Radiographs of tympanic bullae: normal 
radiographs do not rule out bulla disease.• CT or MRI (preferred over radiographs)—
may be required to rule out other causes such 
as otitis media and interna, central causes 
(e.g., ischemic event, neoplasia, inflammatory 
disease).
• Brainstem auditory evoked response—to 
assess cochlear portion of cranial nerve VIII; 
may help to evaluate for otitis media and 
interna since only the vestibular portion of 
cranial nerve VIII is affected with geriatric 
vestibular disease.
• Deafness may, however, be present as an 
unrelated aging change.
 TREATMENT
• Mild disease—usually can manage as 
• Severe disease—patients that cannot 
ambulate or require IV fluid support should 
be hospitalized during the initial stages.
• T reatment supportive, including rehydra-
tion by IV fluids if required.
• Keep recumbent patients warm and dry 
using soft, absorbent bedding and, if 
required, urinary catheter.
• Severe disease—physical therapy, including 
passive manipulation of limbs and moving body 
to alternate sides, may be required initially.
ACTIVITY
Restrict activity as required by the degree of 
disorientation and vestibular ataxia.
DIET
• No modification usually required.
• Nausea, vomiting, and severe disorienta-
tion—initially withhold oral intake, then 
supervised feeding.
Reassure client that although the initial signs 
can be alarming and incapacitating, the 
prognosis for rapid improvement and 
recovery is excellent.
• Sedatives—for severe disorientation and 
ataxia; diazepam 2–10 mg/dog PO or IV q8h, 
acepromazine 0.02–0.05 mg/kg IM, SC, IV 
to maximum of 2 mg, dexmedetomidine 
1–2 μg/kg IV.
• Antianxiety—trazodone approximately 
5 mg/kg PO q8–24h.

Canine and Feline, Seventh Edition  1423
V(continued)  Vestibular Disease, Geriatric—Dogs
• Antiemetic drugs or drugs against motion 
sickness—questionable benefit; dimenhydri-
nate 4–8 mg/kg PO, IM, IV q8h, meclizine 
HCl 25 mg PO q24h, maropitant 1 mg/kg 
SC q24h for up to 5 days or 2 mg/kg PO 
q24h for up to 5 days.
• Glucocorticoids—not recommended since 
do not alter course of the disease; may 
exacerbate concurrent issues (e.g., dehydration).
• Antibiotics—recommended when otitis 
media and interna cannot be ruled out; 
trimethoprim-sulfa 15 mg/kg PO q12h or 
30 mg/kg PO q12–24h; first-generation 
cephalosporin (e.g., cephalexin 10–30 mg/kg 
12.5 mg/kg PO q12h, enrofloxacin 5–20 mg/kg 
PO q24h or divided q12h.
N/A
 FOLLOW-UP
• Neurologic examination of outpatient—
repeat 2–3 days later to confirm stabilization 
and initial improvement.
• Discharge inpatient when able to ambulate 
and resume eating and drinking.
• Fluid and electrolyte imbalances and 
decompensation of preexistent renal 
insufficiency may follow vomiting and/or 
insufficient fluid and food intake.
• Pressure sores/abrasions.
• Improvement of clinical signs usually starts 
within 72 hours with gradual resolution of 
vomiting and improvement of nystagmus and 
vestibular ataxia.
• Head tilt and ataxia—significant improve -
ment usually occurs over 7–10 days; if no 
improvement other causes of peripheral 
vestibular disease should be pursued; mild 
head tilt may persist.
• Most patients return to normal within  
2–3 weeks.
• Recurrence—repeat episodes of geriatric 
vestibular disease can occur on the same or 
opposite side but are uncommon; brief return 
of signs may occur with stress  
(e.g., anesthesia).
N/A
Geriatric dogs affected (mean age suggested 
12.5 years).ZOONOTIC POTENTIAL
N/A
N/A
SYNONYMS
• Benign idiopathic canine peripheral 
• Canine idiopathic vestibular disease/
syndrome.
• Idiopathic canine peripheral vestibular 
disease.
• Old dog vestibular syndrome.
SEE ALSO
ed. St. Louis, MO: Saunders Elsevier, 2015, 
pp. 348–349.
Dewey CW. A Practical Guide to Canine and 
Wiley-Blackwell, 2008, pp. 272–273.
Manson Publishing, 2012, pp. 253–263.

1424  Blackwell’s Five-Minute Veterinary Consult  
VVestibular Disease, Idiopathic—Cats
 BASICS
peripheral vestibular system of cats.
• Unknown.
inner ear, secondary to a disturbance in the 
fluid.
• Sporadic acquired disease.
Species
Cat
Any age; rare in cats <1 year of age.
SIGNS
Limited to signs associated with peripheral 
vestibular disturbance.
Sudden onset of severe disorientation, falling, 
rolling, leaning, vocalizing, and crouched 
posture; tendency to panic when picked up.
• Head tilt—always toward the side of the 
lesion; occasionally disease is bilateral with 
wide, side-to-side excursions of the head 
either without a head tilt or with a mild tilt 
toward the more severely affected side.
• Resting nystagmus—usually horizontal, but 
may be rotatory with the fast phase always in 
direction opposite to the head tilt; with 
bilateral disease, the abnormal nystagmus is 
usually mild or not present, and physiologic 
nystagmus or conjugate eye movements are 
diminished to absent.
• Vestibular ataxia with tendency to roll and 
fall toward the side of the head tilt.
• Preservation of strength and normal 
proprioception; with bilateral disease, patient 
may be reluctant to ambulate, preferring to 
stay in a crouched posture and possible 
wide-based stance.
CAUSES
• Unknown.
• Previous upper respiratory tract infection—
suspected in some patients; relationship not confirmed; in limited necropsy data no 
evidence of inflammation.
May be an increase in cases in the summer 
and early fall, possibly after outbreaks of 
upper respiratory disease; disease can occur 
throughout the year.
 DIAGNOSIS
• Diagnosis made on the basis of acute-
onset peripheral vestibular signs that 
improve relatively rapidly without specific 
• Otitis media and interna (e.g., bacterial, 
parasitic)—may have concurrent ipsilateral 
facial nerve (cranial nerve VII) paresis or 
paralysis, Horner’s syndrome, deafness, 
ruptured tympanic membrane, otitis externa, 
and/or imaging changes in tympanic bulla; 
signs usually not self-limiting.
• Nasopharyngeal polyp(s)—may cause 
unilateral or, much less commonly, bilateral 
peripheral vestibular signs; may have concurrent 
tympanic bulla involvement; signs usually not 
as acute and severe at onset and are not 
• Neoplasia—e.g., squamous cell carcinoma; signs 
usually not acute in onset; may have concurrent 
cranial nerve VII deficit and/or ipsilateral Horner’s 
syndrome; signs not self-limiting.
• Blue-tailed lizard ingestion—southeastern 
United States; thought to produce a similar 
acute, unilateral, peripheral vestibular 
syndrome; vomiting, salivation, irritability, 
and trembling also noted; most patients 
recover without specific treatment.
• Aminoglycoside toxicity, especially 
streptomycin—may cause acute unilateral or 
bilateral peripheral vestibular syndrome and/
or hearing loss; differentiated by history of 
drug use.
• T rauma—overzealous ear flushing; usually 
occurs when cleaning performed under 
general anesthesia or sedation; signs follow 
immediately upon recovery from anesthesia/
sedation.
Normal
IMAGING
• None usually necessary.
radiographs do not rule out bulla disease.
• CT or MRI—occasionally required to rule 
out other causes such as otitis media and 
interna, nasopharyngeal polyp(s) and neoplasia.
Brainstem auditory evoked response—may 
help rule out other causes (e.g., otitis media 
and interna; nasopharyngeal polyp(s), neoplasia); with idiopathic vestibular disease 
hearing not affected since disease limited 
to the vestibular portion of cranial nerve VIII.
 TREATMENT
• Inpatient—severely affected patient may 
require hospitalization for supportive care.
• Mild disease—treatment supportive only.
• Severe disease—may require IV or subcut -
aneous fluids; maintain patient in quiet, 
well-padded cage.
ACTIVITY
Restricted according to the degree of 
disorientation and ataxia.
DIET
Patient may initially be reluctant to eat and 
drink because of disorientation and/or nausea.
Reassure client that, despite initial alarming 
and often incapacitating signs, the prognosis 
for rapid and complete recovery is excellent.
rolling; diazepam 1–5 mg/cat PO q8–12h, 
acepromazine 0.02–0.05 mg/kg IM, SC, IV.
• Antiemetic drugs and drugs against motion 
sickness—questionable benefit; e.g., meclizine 
HCl 12.5 mg PO q24h, maropitant 1 mg/kg 
q24h PO, SC.
do not alter course of the disease.
• Antibiotics—recommended if otitis media 
and interna cannot be ruled out; 
first-generation cephalosporin (e.g., 
cephalexin 15–20 mg/kg PO q12h); drug of 
choice is amoxicillin/clavulanic acid 
(Clavamox 62.5 mg/cat PO q12h, 
Clavaseptin 12.5 mg/kg PO q12h).
 FOLLOW-UP
repeat in approximately 72 hours to 
confirm stabilization and initial improve- 
ment.

Canine and Feline, Seventh Edition  1425
V(continued)  Vestibular Disease, Idiopathic—Cats
• Inpatient—discharge patient when 
able to ambulate and resume eating and 
drinking.
• Marked improvement, especially in resting 
nystagmus starting within 72 hours, with 
progressive improvement of gait and head tilt.
• Patients usually normal within 2–3 weeks.
• Head tilt—final sign to resolve; mild 
residual tilt may remain.• If signs do not improve rapidly, other causes 
of vestibular disease should be pursued.
• Rarely recurs.
SR, Garosi LS, eds., Small Animal Neurological Emergencies. London: 

1426  Blackwell’s Five-Minute Veterinary Consult  
VVomiting, Chronic
  BASICS
Persistent vomiting lasting longer than 5–7 
days or vomiting that occurs intermittently 
several days/week. This condition is usually 
nonresponsive to symptomatic treatment.
• Vomiting occurs when the vomiting center, 
located within the medulla oblongata, is 
activated by the humoral or neural pathway.
• There are four main components to the 
vomiting reflex: (1) visceral receptors within 
the gastrointestinal (GI) tract; (2) vagal and 
sympathetic afferent neurons; (3) chemo­
receptor trigger zone (CRTZ); and (4) 
vomiting center.
• The humoral pathway is mediated via 
activation of the CRTZ and is affected by 
bloodborne triggers such as uremic toxins, 
drug toxicity, and endotoxemia.
• The neural pathway is mediated via 
activation of the vomiting center and is affected 
by disorders associated with obstruction, 
distension, or inflammation of the GI tract.
• All causes of vomiting (including the 
vestibular apparatus and cerebrum) are 
ultimately mediated via the vomiting center.
• Endocrine/metabolic—dehydration, 
electrolyte and acid ­base imbalances.
• Cardiovascular—hypovolemia; electrolyte or 
acid–base imbalances can cause arrhythmias.
• GI—esophagitis and subsequent esophageal 
• Nervous—altered mentation.
• Young animals are more likely to ingest 
foreign bodies; linear foreign bodies are more 
• Confirmed or suspected breed predisposi­
tions—brachycephalic breeds are prone to 
pyloric outflow obstruction secondary to 
mucosal hypertrophy; basenji, German 
shepherd dog, and shar ­pei are prone to 
inflammatory bowel disease (IBD); Rottweiler 
are prone to eosinophilic IBD; Airedale terrier 
prone to pancreatic carcinoma; beagle, 
Bedlington terrier, cocker spaniel, Doberman 
pinscher, Labrador retriever, Skye terrier, and 
standard poodle are prone to chronic 
hepatitis. Yorkshire terrier predisposed to 
intestinal lymphangiectasia.
SIGNS
• Hematemesis, decreased appetite or 
anorexia, and melena, may suggest gastric 
disease.• Diarrhea and profound weight loss may 
suggest intestinal disease.
• Signs such as weakness, polyuria, or 
jaundice may relate to other underlying 
metabolic diseases.
• Weight loss and poor hair coat may indicate 
chronic malnutrition.
• Abdominal palpation may reveal abdominal 
distention, pain, thickened bowel loops, 
lymphadenopathy, or mass effects.
• Tacky mucous membranes and prolonged 
skin tenting if dehydration is present; pale 
membranes if patient is anemic.
• Oral examination may reveal uremic 
ulcerations or sublingual string foreign bodies.
• Rectal examination may detect diarrhea, 
hematochezia, or melena.
CAUSES
Esophageal Disease
• Hiatal hernia (more commonly associated 
with regurgitation).
• Gastroesophageal reflux (more commonly 
associated with regurgitation).
Infectious Disease
• Helicobacter- related gastritis.
• Small intestinal bacterial overgrowth.
• Gastric or intestinal parasites.
• Diabetic ketoacidosis (DKA).
• Electrolyte abnormalities—hypo ­/
hyperkalemia, hyponatremia, hypercalcemia.
Inflammatory Bowel Disease
• Lymphocytic, plasmacytic, eosinophilic, or 
granulomatous.
• Gastritis, enteritis, or colitis.
Obstructive GI Disease
• Chronic hypertrophic pyloric gastropathy.
Neoplastic Disease
• GI lymphoma, adenocarcinoma, fibro­
sarcoma, GI stromal cell tumor.
• Pancreatic adenocarcinoma.
• Gastrin ­secreting tumor (gastrinoma).
• CNS tumors.
• Encephalitis/meningoencephalitis.
• Vestibular disease.
Motility Disorders
• Postgastric dilatation.
• Postsurgical—gastric, duodenal.• Electrolyte imbalances.
• Ileus.
• Drugs (e.g., nonsteroidal anti ­inflammatory 
drugs [NSAIDs], glucocorticoids, chemo­
therapeutics, antibiotics, antifungals).
• Food sensitivity.
• Toxicity.
Additional Causes
• Parasitic (cats)—dirofilariasis, Ollulanus 
tricuspis .
• Inflammatory—cholecystitis, cholangio  ­ 
• Metabolic—hyperthyroidism.
• Functional—constipation/obstipation.
Breed ­associated disease (see Signalment).
  DIAGNOSIS
• Vomiting must first be differentiated from 
• Regurgitation is a passive process and 
occurs without an abdominal component, 
thus localizing disease to the esophagus.
• Vomiting is a centrally mediated reflex 
often preceded by prodromal signs of 
restlessness, nausea, salivation, and repeated 
• Chronic GI bleeding can cause a non ­
regenerative anemia, often with characteristics 
of iron deficiency (microcytosis, hypochromasia, 
thrombocytosis).
• Non­regenerative anemia may also occur 
secondary to chronic metabolic or 
inflammatory diseases.
• Inflammatory conditions may cause 
neutrophilic leukocytosis and monocytosis.
• Eosinophilia can occur from eosinophilic 
IBD, hypoadrenocorticism, and GI parasitism.
• Thrombocytopenia has been reported with 
IBD.
• Dehydration increases the packed cell 
volume and total protein.
• Electrolyte and acid–base imbalances reflect 
severity of losses and can help to localize 
disease.
• Hypochloremic metabolic alkalosis, often 
with hypokalemia, suggests gastric outflow 
• Hyperkalemia suggests hypoadrenocorticism 
or oliguric/anuric renal failure; occasionally, 
enteritis caused by trichuriasis or bacterial 
infection (salmonellosis) mimics hypoadreno ­ 
• Metabolic acidosis is common in 
patients with dehydration, renal failure, 
DKA, and severe gastroenteritis with 
diarrhea.

Canine and Feline, Seventh Edition  1427
V• Increased liver enzyme activity, hypo­
albuminemia, hyperbilirubinemia, 
hypoglycemia, or low urea nitrogen 
concentration suggest hepatic disease.
• Persistent hyperglycemia and glucosuria is 
consistent with diabetes mellitus.
• Hyperglobulinemia may indicate chronic 
• Hypoproteinemia, hypocholesterolemia, 
lymphopenia, and hypomagnesemia occur 
secondary to a protein ­losing enteropathy 
caused by infiltrative intestinal diseases such 
as lymphocytic plasmacytic gastroenteritis, 
neoplasia, histoplasmosis, or intestinal 
lymphangiectasia.
• Urinalysis is used to rule out renal failure 
and DKA.
• Aciduria in the hypokalemic, hypochloremic, 
alkalotic patient suggests gastric outflow 
• Resting cortisol to screen for hypoadreno­
corticism. A resting cortisol <2 μg/dL should 
be followed with an ACTH stimulation test.
• Pancreatic lipase immunoreactivity assay 
may help confirm pancreatitis together with 
supportive history, physical exam findings, 
and ultrasound.
• Serum cobalamin and folate as indicators of 
intestinal absorption.
• Pre­ and postprandial bile acids to screen 
for hepatobiliary dysfunction.
• Fecal testing for GI parasitism.
IMAGING
• Survey radiographs of the abdomen help 
identify foreign bodies, GI distension with 
fluid or gas, and displacement, malposition, 
shape, and/or size changes of abdominal 
organs.
• Survey radiographs of the thorax are used to 
evaluate for pulmonary metastases, gross 
esophageal abnormalities, or infectious 
disease.
• A barium upper GI series can be used to 
identify foreign bodies, GI wall masses or 
infiltrative disease, mucosal ulceration, 
delayed gastric emptying, and motility 
disorders; however, the procedure is relatively 
insensitive for detection of mucosal 
• Abdominal ultrasonography to identify 
abnormalities of the liver, gallbladder, 
kidneys, pancreas, GI tract, and mesenteric 
• CT and MRI further evaluate for 
abnormalities of abdominal organs.
• Gastroduodenoscopy—allows direct 
inspection of the gastric and intestinal lumen 
to identify gross mucosal lesions and foreign 
bodies and provides a minimally invasive 
method of biopsy to evaluate for microscopic 
disease. Limitations of endoscopy include the 
working length of the endoscope (unable to access the jejunum in large ­breed dogs) and 
depth of the biopsies.
• Laparoscopy or exploratory laparotomy is 
used for more extensive diagnostic and 
therapeutic procedures.
  TREATMENT
Specific treatment should be aimed at 
eliminating the underlying cause in 
conjunction with supportive therapy. Care 
may be inpatient or outpatient depending 
on the case.
• If vomiting is intractable, stop oral intake 
of food and water for 12–24 hours or until 
the vomiting episodes are better controlled 
with antiemetics.
• Use crystalloid fluid therapy to replace 
deficits and to provide for maintenance and 
• Supplement potassium if hypokalemia is 
present; 20 mEq of KCl/L of fluid can be 
safely added for replacement and mainten­
ance; use higher concentrations if severe 
hypokalemia is present.
DIET
• Debilitated patients and those in poor 
nutritional condition may need supplemental 
parenteral or enteral nutrition.
• Dietary therapy for patients with suspected 
food allergy or with IBD should use an 
elimination diet containing a single, novel 
protein source or a hydrolyzed diet.
Use surgical treatment if uncontrolled 
hemorrhage, obstruction, or perforation is 
• Antisecretory drugs such as H2­receptor 
blockers (e.g., famotidine, ranitidine) or 
proton pump inhibitors such as omeprazole 
(more potent)—famotidine 0.5–1 mg/kg PO, 
IV, or SC q12h; ranitidine 1–2 mg/kg PO, IV 
q12h; omeprazole 0.7–1.5 mg/kg PO q12h.
• Protectants such as sucralfate 0.25–1 g/dog 
PO q6–12h or 0.25 g/cat PO q6–12h to 
accelerate gastric mucosal healing; can be 
used with antisecretory drugs for patients 
with evidence of upper GI bleeding (e.g., 
hematemesis or melena).
• Antibiotics—indicated for treatment of 
Helicobacter ­associated gastritis, small intestinal bacterial overgrowth (SIBO), and as an adjunct 
to corticosteroids in the treatment of IBD.
• Metronidazole—may be used at 10 mg/kg 
PO q12h in conjunction with corticosteroids 
to treat IBD, although evidence of direct 
benefit of this approach is currently lacking.
• Antibiotic ­responsive enteropathy 
(tylosin ­responsive enteropathy)—tylosin is 
the drug of choice administered at 10–40 mg/
kg q12h for 8–12 weeks. Alternative option is 
metronidazole 10 mg/kg q12h for 8–12 
weeks, although tylosin may be superior for 
• Use corticosteroids in conjunction with 
dietary changes to treat biopsy ­confirmed 
IBD; azathioprine, chlorambucil, or 
cyclosporine can also be used in patients with 
poor response to corticosteroids alone or to 
decrease the dosage of steroids required to 
control symptoms. Avoid the use of more 
than two immunomodulatory drugs given 
• Prokinetic drugs (e.g., metoclopramide, 
cisapride, or erythromycin) are used to treat 
delayed gastric emptying not associated with 
obstructive disease. Metoclopramide 
0.2–0.5 mg/kg IV, IM, PO q6–8h; more 
effective as a CRI of 1–2 mg/kg q24h in 
• Pyrantel pamoate is effective for 
Physaloptera ; fenbendazole is effective for 
Ollulanus .
• Iron supplementation for animals with 
chronic GI bleeding that develop microcytic 
• Surgery and/or chemotherapy for neoplasia, 
depending on the tumor type and location.
• Paraneoplastic hypersecretion of gastric acid, 
as occurs with mastocytosis and gastrin ­
secreting pancreatic tumors, is best treated 
with antisecretory drugs (e.g., omeprazole).
• Reserve antiemetics for patients with 
persistent vomiting unresponsive to treatment 
of the underlying disease. Maropitant 1 mg/kg 
SC q24h, 2 mg/kg PO q24h. Chlorpromazine 
0.5 mg/kg SC, IM q6–8h. Ondansetron 
0.2–0.5 mg/kg SC, IV q8–12h, 0.5–1.0 mg/kg 
PO q12h.
• Vomiting caused by chemotherapy is best 
treated with ondansetron 0.5–1 mg/kg IV, 
PO given 30 minutes before chemotherapy.
N/A
• Do not give α­adrenergic blockers such as 
chlorpromazine to dehydrated patients as 
they can cause hypotension.
• Use antiemetics with caution, as they can 
mask the underlying problem.
• Metoclopramide can cause lethargy, restless­
ness, agitation, and other behavioral changes, 
• Corticosteroids are immunosuppressive and 
are a risk factor for development of GI (continued)  Vomiting, Chronic

1428  Blackwell’s Five-Minute Veterinary Consult  
Vulceration; use caution when treating IBD 
with corticosteroids at high dosages or for 
long periods.
• Azathioprine and chlorambucil are 
myelotoxic; monitor CBCs for neutropenia and 
thrombocytopenia every 2 weeks for the first 
month of treatment and monthly thereafter.
• Cyclosporine can exacerbate vomiting and 
diarrhea when used at high dosages; use with 
caution in patients with renal disease.
• Do not use anticholinergics as antiemetics, 
as they can exacerbate vomiting by causing 
gastric atony and gastric retention.
• Metoclopramide and cisapride are 
contraindicated in patients with GI 
Ranitidine interferes with hepatic metabolism of 
theophylline, phenytoin, and warfarin, and 
should not be used concurrently with these drugs. 
Avoid use of cimetidine because it is a weak 
H2­receptor antagonist and is a potent inhibitor 
of the cytochrome P450 enzyme pathway.
N/A
  FOLLOW-UP
• Frequency of vomiting.
• Body weight; body condition score.PREVENTION/AVOIDANCE
N/A
N/A
N/A
Dependent on underlying cause.
N/A
SYNONYMS
N/A
SEE ALSO
• Food Reactions (Gastrointestinal), Adverse.
• Hypertrophic Pyloric Gastropathy, Chronic.• Ileus.
• CRTZ = chemoreceptor trigger zone.
• DKA = diabetic ketoacidosis.
drug.
• SIBO = small intestinal bacterial 
Guilford WG, Center SA, Williams DA, 
Meyer DJ. Chronic gastric diseases. In: 
Strombeck’s Small Animal Gastroenterology, 
3rd ed. Philadelphia, PA: Saunders, 1996, 
pp. 275–302.
Simpson K. Diseases of the stomach. In: 
Ettinger SJ, Feldman EC, eds., Textbook 
of Veterinary Internal Medicine, 8th ed. 
pp. 1495–1516.
Author  John M. Crandell
available onlineVomiting, Chronic  (continued)

Canine and Feline, Seventh Edition  1429
VVon Willebrand Disease
  BASICS
• Primary hemostatic defect caused by a 
quantitative or functional deficiency of von 
Willebrand factor (VWF).
• Clinical expression varies from a mild to 
severe bleeding diathesis.
• VWF is an adhesive plasma protein 
required for platelet binding at sites of 
small vessel injury. In addition, plasma 
VWF is a carrier protein for coagulation 
factor VIII.
• A lack of VWF impairs platelet adhesion 
and aggregation, especially at vascular sites 
under high shear stress (e.g., arterial vessels). 
The largest molecular weight (MW) forms of 
VWF demonstrate highest reactivity in 
supporting platelet–collagen interactions.
• VWF deficiency may cause spontaneous 
hemorrhage, prolonged post-traumatic 
hemorrhage, and ultimately blood-loss 
anemia.
• Spontaneous hemorrhage—typically 
manifests as bleeding from mucosal surfaces.
GENETICS
• An autosomal trait; both males and females 
express and transmit the defect with equal 
• Expression pattern of severe forms (types 
2 and 3 von Willebrand disease [VWD]) is 
recessive; the milder form (type 1 VWD) 
appears to be recessive or incomplete 
dominant.
• The most common hereditary hemostatic 
defect in dogs.
None
• Three type classifications are found in dogs; 
a single type predominates within each 
affected breed.
• Type 1 VWD (mild to moderate signs)—
quantitative deficiency. Low VWF concentra-
tion (VWF:Ag )with proportionate decrease 
in VWF function. Type 1 is the most 
common classification:
◦ Breeds—Airedale terrier, Akita, basset 
hound, Bernese mountain dog, dachshund, 
Doberman pinscher, German shepherd dog, 
golden retriever, greyhound, Irish wolfhound, 
Manchester terrier, miniature pinscher, 
Pembroke Welsh corgi, poodle, and 
sporadic cases in other purebred and 
mixed-breed dogs.• Type 2 VWD (severe signs)—quantitative 
and functional protein defect; low VWF:Ag 
with profound lack of activity due to absence 
of high MW multimers:
◦ Breeds—German wirehaired and 
shorthaired pointers.
• Type 3 VWD (severe signs)—complete lack 
of plasma VWF:
◦ Breeds—Chesapeake Bay retriever, Dutch 
kooiker, Scottish terrier, Shetland sheepdog, 
and sporadic cases in dogs of other breeds.
• Severe (types 2 and 3 VWD) typically 
manifests by 3–6 months of age.
• Milder forms typically demonstrate 
abnormal bleeding after surgery or trauma, or 
in association with another condition that 
impairs hemostasis.
SIGNS
• Hemorrhage from mucosal surfaces—
epistaxis, gastrointestinal hemorrhage, 
hematuria, vaginal hemorrhage, gingival 
• Prolonged bleeding after surgery or trauma.
• Blood loss and/or iron-deficiency anemia, if 
prolonged hemorrhage.
• Petechiae rarely present.
CAUSES
Hereditary VWD is caused by mutations that 
impair VWF synthesis, release, or stability.
Acquired disease conditions or drug therapy 
that impair platelet function may exacerbate 
clinical signs of VWD.
  DIAGNOSIS
• Acquired coagulation factor deficiency 
(often associated with liver disease, vitamin K 
deficiency, or disseminated intravascular 
coagulation [DIC]).
• Acquired platelet function defects (often 
associated with drug therapy, uremia, hyper  - 
proteinemia).
• Hereditary coagulation factor deficiencies 
(see Coagulation Factor Deficiency).
• Hereditary platelet function defects (see 
• Regenerative anemia develops after 
blood loss.
has experienced acute, massive bleeding.
clotting time, activated partial thromboplastin 
time, prothrombin time, thrombin clot time, fibrinogen concentration)—within reference 
• Clinical diagnosis based on specific 
measurement of plasma VWF:Ag:
◦ VWF:Ag <50% indicates VWF 
deficiency, but clinical signs of abnormal 
bleeding typically develop in animals with 
VWF:Ag < 25%.
◦ Types 1 and 2 VWD are characterized by 
low VWF:Ag, whereas type 3 VWD is 
defined as a complete absence of detectable 
protein (VWF:Ag <0.1%).
• Types 1 and 2 VWD are differentiated with 
functional and/or structural VWF analyses:
◦ Von Willebrand factor collagen binding 
assay (VWF:CBA) is a functional measure 
of VWF/collagen affinity. Dogs with type 2 
VWD have a relative lack of VWF:collagen 
binding activity (CBA) compared to VWF:Ag, 
resulting in a protein concentration to 
function ratio >2:1. Dogs with type 1 
VWD have proportionate protein 
concentration and function.
• VWF multimer structure is visualized on 
Western blots. Dogs with type 2 VWD lack 
the highest MW forms.
• Buccal mucosal bleeding time (BMBT) and 
the platelet function analyzer-100 are 
point-of-care screening tests whose endpoints 
are prolonged in patients with platelet 
aggregation defects or VWF deficiency. 
Prolongation is also found in patients with 
thrombocytopenia, anemia, or changes in 
• BMBT (expected values 2–4 minutes)—
typical values for type 1 VWD = 5–10 
minutes, types 2 and 3 VWD >12 minutes.
• PFA-100 closure times (expected ADP/
collagen closure time <120 seconds): typical 
values for type 1 VWD = 150–300 seconds, 
types 2 and 3 VWD >300 seconds.
Hemorrhage is the only associated 
abnormality. Morbidity and mortality are 
caused by blood loss or hemorrhage into 
critical sites (i.e., CNS, respiratory tract).
  TREATMENT
plasma, fresh frozen plasma, and cryopreci -
pitate will supply VWF .
• Component therapy (fresh frozen plasma, 
10–12 mL/kg, IV) or cryoprecipitate (1 unit 
per 10 kg body weight, IV) is best for surgical 
prophylaxis and non-anemic patients, to 
prevent red cell sensitization and volume 
overload.
• Patients with severe VWD may require 
repeated transfusions to control or prevent 

1430  Blackwell’s Five-Minute Veterinary Consult  
VSURGICAL CONSIDERATIONS
• Preoperative transfusion should be given just 
before the procedure. Peak VWF is obtained 
immediately after transfusion, with values falling 
to baseline by 24 hours after a single dose.
• Cage rest and close monitoring (serial HCT 
and examination of surgical site) for 24 hours 
after surgery are ideal to confirm adequate 
hemostasis. Management of severe VWD 
typically requires at least one postoperative 
• Desmopressin acetate (DDAVP) is a 
vasopressin analogue that can be given 
preoperatively to dogs with mild to moderate 
type 1 VWD to enhance surgical hemostasis. 
Dosage is 1  μg/kg SC, given 30 minutes 
before surgery.
• Response is variable; transfusion should be 
available if DDAVP alone does not prevent 
bleeding.
Avoid drugs with anticoagulant or antiplatelet 
effects: NSAIDs, sulfonamide antibiotics, 
heparin, wafarin, hetastarches, estrogen, 
  FOLLOW-UP
Observe closely for hemorrhage associated 
with trauma or surgical procedures.
PREVENTION
• Screen dogs preoperatively to determine baseline 
VWF:Ag in breeds or lines with high prevalence 
of VWD. The risk of abnormal bleeding is 
greatest for dogs with VWF:Ag <25%.• Clinically affected dogs should not be bred. 
Carriers of VWD can be identified based on 
low VWF:Ag (<50%). However, values for 
carrier and clear dogs may overlap at the low 
end of the reference interval (50–70% 
VWF:Ag). Commercial laboratories offer 
genetic tests to detect specific VWF 
mutations in several breed-variants of VWD. 
Dogs that are heterozygous for a specific 
mutation are considered VWD “carriers” 
and homozygotes are considered VWD 
“affected.”
• Selective breeding practices can reduce or 
eliminate VWD from an affected pedigree. 
Breeding two clear parents is ideal because all 
offspring are expected to be clear. Breeding 
one clear and one carrier parent may be 
acceptable, with the clear pups produced 
from these matings used for subsequent 
breeding. Carrier-to-carrier matings are 
inadvisable because they are most likely to 
produce clinically affected offspring.
• Most dogs with mild to moderate VWD 
have good quality of life and require minimal 
or no special treatment.
• Dogs with more severe forms require 
transfusion for surgery and should be 
transfused if supportive care fails to control a 
spontaneous bleed. Most of these dogs can be 
maintained comfortably in pet homes.
• The development of any disease condition 
that impairs platelet function may exacerbate 
the bleeding tendency of VWD. Common 
conditions include thrombocytopenia, 
endocrinopathy (hypothyroidism, hypoadreno -
corticism), hyperproteinemia, and uremia.• Acquired VWD occurs in humans with 
aortic stenosis, and features of type 2 VWD 
have been reported in cavalier King Charles 
spaniels with mitral valve disease.
See Prevention for breeding recommendations.
SYNONYMS
VWF protein was formerly referred to as 
factor VIII-related antigen.
• DDAVP = deamino-8- d-arginine vasopressin.
• MW = molecular weight.
drug.
• PFA = platelet function assay.
• VWF:Ag = von Willebrand factor antigen.
• VWF:CBA = von Willebrand factor 
collagen binding assay.
Boudreaux MK. Characteristics, diagnosis, 
and treatment of inherited platelet disorders 
in mammals. J Am Vet Med Assoc 2008, 
233:1251–1259.
Venta PJ, Li J, Yuzbasiyan-Gurkan V, Brewer 
GJ, Schall W. Mutation causing vWD in 
Scottish terriers. J Vet Intern Med 2000, 
14:10–19.
Wardrop KJ, Brooks MB. Plasma products. 
In: Yagi K, Holowaychuk MK, eds., Manual 
of Veterinary T ransfusion Medicine. 
Hoboken, NJ: John Wiley & Sons, 2016, 
pp. 43–54.
available onlineVon Willebrand Disease  (continued)

Canine and Feline, Seventh Edition  1431
WWeight Loss and Cachexia
  BASICS
• Weight loss—loss of body weight (BW) 
resulting from reduction in fat mass and/or 
lean body mass.
• Lean body mass (LBM)—tissues other than 
adipose tissue (muscle, organs, bone); skeletal 
muscle is most dynamic component.
• Simple starvation—acute or chronic 
decrease in food intake below caloric require­
ments in an otherwise healthy animal; adaptive 
responses allow loss of fat mass over LBM.
• Cachexia—weight loss and tissue wasting 
secondary to underlying disease (e.g., cancer, 
heart failure, inflammatory conditions). 
Hallmark is loss of LBM; fat mass is variably 
affected.
• Sarcopenia—age ­related muscle loss and 
decline in muscle quality. Can occur without 
loss of BW.
Weight Loss and Simple Starvation
• Decreased caloric intake or increased energy 
expenditure results in negative energy balance.
• In otherwise healthy animals, compensation 
such as reduced metabolism and a shift 
toward lipid ­based energy production reduce 
protein catabolism by up to two ­thirds.
Cachexia
• Occurs secondary to acute or chronic 
• Pathophysiology better evaluated in 
humans than dogs and cats:
◦ Upregulation of inflammatory cytokines 
(e.g., interleukin ­6 [IL ­6], tumor necrosis 
factor ­α [TNF ­α]), catecholamines, neuro  ­ 
hormones and cortisol.
◦ Increases in oxidative stress; activation of 
catabolic pathways (e.g., ubiquitin ­
proteasome system).
◦ Decreases in anabolic factors (e.g., 
growth hormone [GH], insulin ­like growth 
factor I [IGF ­1]).
• Results in dysregulation of appetite, insulin 
resistance, increased muscle catabolism, and 
impaired tissue synthesis.
• Increased basal metabolic rate and 
metabolic inefficiencies contribute to tissue 
wasting.
• Secondary anorexia aggravates malnutrition 
and muscle catabolism.
Sarcopenia
• Occurs during normal aging in the absence 
of disease; may occur alongside cachexia.
• Inflammation, oxidative stress, and 
catabolic pathway upregulation likely 
contribute to LBM loss similarly to cachexia.
• Musculoskeletal—progressive loss of LBM 
causes weakness, fatigue, and exercise intolerance.• Hemic/lymphatic/immune—serous atrophy 
of fat can rarely cause bone marrow hypoplasia 
• Underlying diseases leading to cachexia can 
affect all body systems.
GENETICS
N/A
Weight Loss
• Congestive heart failure (CHF)—42.5% of 
dogs; 34% of cats.
• Cancer—5.5–69% of dogs; 60% of cats.
• Chronic kidney disease (CKD)—28.9–
55% of dogs; 36–81% of cats.
Cachexia
• CHF—48.3–54% of dogs; unknown in 
cats.
• Cancer—35% of dogs; 91% of cats.
• CKD—28.9% of dogs (weight loss/
cachexia); 81% of cats.
N/A
Species
N/A
Risk of sarcopenia and cachexia increases with 
age.
None
SIGNS
• Body Condition Score (BCS)—palpation/
observation of fat deposits over ribs, lumbar 
spine, abdominal fat pad (cats), and tail base:
◦ Scored 1 (severe fat loss) to 9 (obesity).
• Muscle Condition Score (MCS)—palpation/  
visualization of muscle of spine, skull, 
scapulae, and wings of the ilia:
◦ Graded as none, mild, moderate, or 
severe muscle wasting.
• BCS and MCS must be evaluated separately, 
as loss of LBM can occur without loss of fat 
or change in BW.
• Appetite may be normal, increased, 
decreased, or absent depending on cause.
• History should focus on identifying 
underlying disease (see Causes).
• Decreased BW compared to historical 
weights (corrected for hydration changes, 
fluid accumulation, etc.).
• Decreased absolute or relative BCS (fat loss) 
and/or MCS (LBM loss).
• Other physical examination findings may 
indicate underlying disease process (see Causes).CAUSES
Physiologic Negative Energy Balance
• Simple starvation.
• Competition in a multi ­pet household.
• Increased physical activity.
• Prolonged or extreme cold environment.
• Pregnancy or lactation.
Anorexia/Pseudoanorexia
• Inability to smell, prehend, or chew food.
• Nausea.
• Pain or anxiety.
• Iatrogenic (e.g., drug side effects).
Maldigestive/Malabsorptive
• Intestinal neoplasia (lymphoma, carcinoma, 
sarcoma).
• Age­related decreases in digestive function.
• Severe intestinal parasitism.
• Infiltrative fungal disease (e.g., histoplasmosis).
• Protozoal (e.g., Toxoplasma gondii , Neospora 
caninum ).
• Feline leukemia virus/feline immunodeficiency 
virus (cats).
Metabolic
• Organ failure (e.g., cardiac, hepatic, or 
renal failure).
• Hypo ­ or hyperadrenocorticism.
• Cancer.
Excessive Nutrient Loss or Consumption
• Protein ­losing enteropathy.
• Protein ­losing nephropathy.
• Extensive skin lesions (e.g., burns).
• Chronic effusive disease (e.g., chylothorax).
• Increased catabolism (e.g., fever, infection, 
inflammation, cancer).
Neuromuscular
• Lower motor neuron disease.
• Myopathy/myositis.
• CNS disease—usually associated with 
anorexia or pseudoanorexia.
• Age.
  DIAGNOSIS
Evaluate BW, BCS, and MCS (compare to 
historical values).
• Increased appetite may indicate physiologic, 
maldigestive/malabsorptive, or metabolic cause.

1432  Blackwell’s Five-Minute Veterinary Consult  
W• Fever may indicate inflammatory or 
infectious cause.
• Laboratory tests may indicate underlying 
cause.
• Low hematocrit, low albumin, increased 
BUN, and increased BUN to creatinine ratio 
may be associated with malnutrition.
• Determined by most likely differential 
diagnoses (see Causes).
• Serum T4 in any cat >5 years old.
• Rule out infectious (parasitic, protozoal, 
viral, and fungal) causes:
◦ Fungal antigen testing, FeLV/FIV, fecal 
centrifugal flotation, etc.
• Serum trypsin ­like immunoreactivity (TLI), 
cobalamin and folate for maldigestive/
absorptive disease.
• Fecal alpha ­1 protease inhibitor level for 
protein ­losing enteropathy.
• ACTH stimulation test for hypoadreno  ­ 
• Pre­ and postprandial serum bile acids for 
hepatobiliary disease.
• Urine protein:creatinine ratio for protein ­
losing nephropathy.
IMAGING
• Thoracic/abdominal radiographs, 
abdominal ultrasound, CT, and/or 
echocardiography may help identify 
• Ultrasound, CT, or dual energy x ­ray 
absorptiometry (DEXA) might be used to 
approximate LBM.
Vary per suspected underlying cause.
Histopathology—cachexia may cause 
preferential atrophy of type II myofibers.
  TREATMENT
T reat the underlying disease and provide 
appropriate nutritional support.
• Depends on hemodynamic stability, 
voluntary food intake, and underlying disease 
type/severity.
• Anorexic patients refractory to supportive 
care should be hospitalized or managed as 
outpatients with a feeding tube.
• Nursing needs depend on underlying disease.
• Daily cleaning, regular flushing, and 
monitoring of feeding tubes to prevent 
infection/clogging.
• Debilitated patients with severe cachexia 
should have adequate padding and be rotated 
frequently to prevent decubital ulcers.ACTIVITY
• Physical therapy, exercise, and rehabilitation 
may slow cachexia/sarcopenia progression:
◦ Increase caloric intake appropriately.
DIET
• Resting energy requirements (RER) = 70 
kcal × kg BW0.75; may need to exceed RER in 
cachectic patients, if tolerated:
◦ Maintenance energy requirement [MER] 
for neutered adult dog: 1.6 × RER, but may 
exceed 2.0–3.0 × RER in individual 
patients.
◦ MER for neutered adult cat: 1.2 × RER, 
but may be higher in individual patients.
• Unless contraindicated, exceed Association 
of American Feed Control Officials (AAFCO) 
protein minimum in cachectic patients:
◦ Dogs—4.5 g/100 kcal; cats—instead of: 
6.5 g/100 kcal.
◦ Most critical care, performance, and 
growth diets are high in protein and fat.
◦ Kitten foods may be suitable for adult 
cats; cat foods may be suitable for dogs.
• Prolonged anorexia—deliver 25–33% of 
RER on day 1; gradually increase to 100% 
RER over 3–5 days, if tolerated:
◦ Monitor serum potassium, phosphorus, 
and magnesium during refeeding; 
supplement if needed.
Oral Nutrition
• Preferred if patient is physically able to 
ingest, digest and absorb nutrients.
• To increase voluntary food intake, offer 
palatable food several times daily; offer the 
patient’s usual food; offer moist food unless 
dry is preferred; offer food warmed to body 
• Consider diets enriched with eicosapen­
taenoic acid (EPA) and docosahexaenoic acid 
(DHA) for cachectic patients or those with 
inflammatory conditions (e.g., therapeutic 
diets for arthritis or dermatologic conditions):
◦ Most diets provide less than recommended 
EPA/DHA amounts (see below); additional 
supplementation may be beneficial.
• If underweight patients refuse therapeutic diets 
(e.g., renal diet), try alternate brand or texture, 
add broth or other palatability enhancer:
◦ Adequate intake of a maintenance diet is 
typically preferable to inadequate intake of 
a therapeutic diet.
• Consider appetite stimulants (see 
• Forced feeding is rarely effective and is not 
recommended due to high risk of aspiration.
Enteral Nutrition
• Preferred if patient is anorexic/pseudo ­
anorexic but can digest and absorb nutrients.
• Place feeding tubes as far proximal in the 
GI tract as tolerated.
• Nasoesophageal or nasogastric tubes 
(5–12Fr) can be used temporarily. Due to 
small tube size, only liquid diets can be used.• Esophagostomy (12–18Fr) or gastrostomy 
tubes (16–24Fr) are semi ­permanent:
◦ Preferred over nasogastric tubes for 
outpatient management.
◦ Allow higher caloric ­density slurry diets, 
therapeutic diets, medication, and oral 
water administration.
• Liquid/slurry feedings q6–8h; initial 
feedings <10 mL/kg/feeding.
• Jejunostomy or gastro ­jejunostomy tubes 
(5–8Fr) are more difficult to place and manage, 
and require liquid diets fed via chronic infusion:
◦ Rarely indicated.
Parenteral Nutrition
• Only if enteral feeding is contraindicated.
• If required, recommend referral to an 
appropriate tertiary facility.
• Feeding tube management and expect­
ations, if considering placement.
• See Expected Course and Prognosis.
• If surgery is indicated, consider placing a 
feeding tube at that time.
• Severe cachexia or weight loss (especially if 
albumin is low) may prolong healing.
• Appropriate medications for underlying 
cause (if identified).
• Therapies targeting catabolic pathways are 
currently being investigated.
Appetite Stimulants
• Adjust selection and dosage based on 
• Mirtazapine: 7.5 and 15 mg tablets; 2% 
transdermal suspension (cats):
◦ Cats: 1.88 mg/cat PO q24–48h; 2 mg/
cat transdermally q24–48h.
◦ Dogs: 1–30 mg/dog PO q8–24h; 
recommend 1 mg/kg PO q8–12h.
• Capromorelin: 30 mg/mL oral suspension:
◦ Dogs: 3 mg/kg PO q24h.
◦ Extra ­label dose not established in cats 
(6 mg/kg tolerated).
◦ Also increases IGF ­1 secretion.
Omega-3 Fatty Acids
• Fish oil, krill oil, omega ­3 supplements:
◦ Vary widely in EPA and DHA content; 
check each supplement individually.
• Dogs and cats—40 mg/kg/day EPA + 25 
mg/kg/day DHA:
◦ Avoid fish oil supplements with vitamins 
A and D if using at this dose.
N/AWeight Loss and Cachexia  (continued)

Canine and Feline, Seventh Edition  1433
WPRECAUTIONS
T reatments for underlying diseases may cause 
anorexia, nausea.
Mirtazapine can cause serotonin syndrome if 
combined with multiple other medications, 
including selective serotonin reuptake 
inhibitors (e.g., fluoxetine) and monamine 
oxidase inhibitors (e.g., selegeline).
N/A
  FOLLOW-UP
• Appropriate monitoring for underlying 
• Precisely  monitor food intake and BW to 
ensure daily intake of RER/MER.
• Serial monitoring of BW, BCS, MCS at 
every visit .
• Early recognition of loss of BW and/or 
LBM and early intervention are key in 
preventing debilitation:
◦ Perform thorough nutritional assessment 
at each visit and implement nutritional 
interventional plan when necessary.
◦ Perform diagnostic workup to identify 
underlying cause of unintended weight loss.
• Aggressive management of diseases 
associated with cachexia.
T ube feeding—infection, vomiting, 
regurgitation and/or diarrhea; tube 
displacement; aspiration; peritonitis 
(gastrostomy or jejunostomy tubes).
• Provision of nutrition to cachectic patients 
without addressing the underlying cause is 
rarely successful in correcting the loss of body 
tissues.• Weight loss, LBM loss, or poor body or 
muscle condition are associated with shorter 
survival in veterinary cardiac, CKD and 
cancer patients.
N/A
Cachexia and sarcopenia are more common 
in geriatric patients.
N/A
Lactation and pregnancy may cause weight 
loss due to increased calorie expenditure.
SYNONYMS
SEE ALSO
• AAFCO = Association of American Feed 
• BCS = body condition score.
• BW = body weight.
• DEXA = dual energy x ­ray absorptiometry.
• DHA = docosahexaenoic acid.
• EPA = eicosapentaenoic acid.
• IGF­1 = insulin ­like growth factor I.
• IL­6 = interleukin ­6.
• LBM = lean body mass.
• MER = maintenance energy requirement.
• MCS = muscle condition score.
• RER = resting energy requirements.• TLI = trypsin ­like immunoreactivity.
• TNF ­α = tumor necrosis factor ­α.
• To find a veterinary nutritionist qualified to 
assist in formulating homemade therapeutic 
or maintenance diets: http://www.ACVN.org
• To find a certified veterinary rehabilitation 
professional: https://rehabvets.org/directory.
lasso
• Information on small animal nutrition 
guidelines, body condition scoring, and 
muscle condition scoring: https://www.wsava.
org/Guidelines/Global ­Nutrition ­Guidelines
Eirmann L. Esophagostomy feeding tubes in 
dogs and cats. In: Chan, D.L. ed., 
Nutritional Management of Hospitalized 
Small Animals. Chichester: John Wiley & 
Sons, 2015, pp. 29–40.
Freeman LM. Cachexia and sarcopenia. In: 
Ettinger SJ, Feldman EC, Côté E, eds., 
739–744.
Freeman LM. Cachexia and sarcopenia: 
emerging syndromes of importance in dogs 
and cats. J Vet Intern Med 2012, 26:3–17.
Johnson LN. Recognizing, describing, and 
managing reduced food intake in dogs and 
cats. J Am Vet Med Assoc 2017, 
251:1260–1266.
Larsen JA. Enteral nutrition and tube feeding. 
In: Fascetti AJ, Delaney SJ, eds., Applied 
Veterinary Clinical Nutrition. Ames, IA: 
Wiley ­Blackwell, 2012, pp. 329–352.
Authors  Laura Rayhel and Valerie J. Parker
Dorothy P . Laflamme.
available online(continued)  Weight Loss and Cachexia

1434  Blackwell’s Five-Minute Veterinary Consult  
WWest Nile Virus Infection
  BASICS
OVERVIEW
• Acute to inapparent viral disease with 
neurologic manifestations caused by West 
Nile virus (WNV), a member of the family 
Flaviviridae, genus Flavivirus .
• Geographic distribution of virus is North, 
Central, South America, Africa, Asia, 
southern Europe, and Australia (Kunjin 
virus).
• Natural route of infection is through bite of 
numerous species of mosquitoes depending 
upon geographic location. Infection produces 
a low-level viremia, insufficient for dogs to be 
an amplifying host; antibody detectable by 
day 7 post infection.
• Natural infections not limited by species or 
age.
• Seroprevalence varies widely with 
geographic region (3–96%).
SIGNS
• High percentage of dogs show no clinical 
signs—no experimentally infected dogs have 
shown clinical signs.
• Febrile response 104–108°F (40.3–42.2°C) 
3–6 days post infection.
• In the rare affected dog, common signs are 
ataxia, depression, anorexia, tremors, conscious 
proprioceptive deficits, seizures, weakness, 
flaccid paralysis; polyarthritis and myocarditis 
also reported.
• Neurologic disease caused by WNV.
• Outdoor dogs much greater odds of being 
seropositive than indoor dogs; high 
seroprevalence in coyotes.
• Stray dogs at greater odds of being 
seropositive than owned dogs.
• Lineage 1 virus more neurovirulent (all 
North American isolates) than lineage 
2 (Africa).
• Yearly fluctuation of infections linked to 
density of mosquito populations.
  DIAGNOSIS
• On an individual basis, signs of WNV-
induced neurologic disease are indistinguish-
able from signs associated with various 
“arbovirus” infections, e.g., eastern equine 
encephalitis (EEE), Venezuelan equine 
encephalitis (VEE), La Crosse.
• Other considerations—rabies, canine 
distemper, neosporosis, toxoplasmosis, pseudorabies, encephalomyocarditis virus, 
meningoencephalitis of unknown etiology 
(MUE).
• Serial sampling may show drop in leuko- 
cytes but may remain within normal.
• Minimal viremia makes detection of agent 
in acute phase unlikely; test of choice is 
reverse transcriptase PCR (RT-PCR) for 
WNV specifically or for arboviruses in 
general; urine may be PCR positive for a 
longer period post infection than whole 
blood.
• Acute and convalescent serum samples 
should be collected for IgM ELISA test and/
or virus neutralization assays.
• For post-mortem testing—RT-PCR and/or 
• CSF—no significant findings (one report).
• Gross lesions not present in limited number 
of dogs necropsied (one had epicarditis).
• Histologic lesions in brain—mild, 
multifocal, nonsuppurative meningo -
encephalitis (lymphocytic to lymphohistio-
cytic perivascular infiltrates predominantly in 
gray matter).
  TREATMENT
Supportive therapy for neurologic 
• Antipyretics may decrease fever.
• Anticonvulsant medications, as indicated.
  FOLLOW-UP
Vaccines available for horses, have not been 
approved for dogs.
• West Nile virus can infect numerous species 
including humans; however, the insect vector 
is generally necessary for transmission and the 
viremia is too low in infected dogs to serve as 
host for infecting feeding mosquitoes.• Care should be taken if necropsy is done, as 
infectious viral particles may be present in 
tissue samples.
RISK TO OTHER ANIMALS
Virus is not transmitted from infected dog to 
other animals. Clinical case of WNV should 
be noted as indicative of infected mosquitoes 
in the area.
• EEE = eastern equine encephalitis.
etiology.
• VEE = Venezuelan equine encephalitis.
• WNV = West Nile virus.
http://npic.orst.edu/pest/mosquito/wnv.html
Njaa BL. Emerging viral encephalitides in 
dogs and cats. Vet Clin Small Anim 2008, 
38:863–878.

Canine and Feline, Seventh Edition  1435
WWhipworms (Trichuriasis)
  BASICS
OVERVIEW
• The whipworm, Trichuris , infects the 
cecum of dogs ( T. vulpis ) and cats 
(T. campanula  and T. serrata ); feline 
trichuriasis is extremely rare in continental 
• Life cycle is direct; infection is acquired by 
ingestion of larvated eggs; infective eggs can 
persist in environment for months to years.
bloody diarrhea and large bowel inflammation.
• Clinical signs can occur before patency, i.e., 
before eggs are shed in feces; prepatent period 
is approximately 70–90 days.
• No extraintestinal migration occurs.
SIGNS
• Range from asymptomatic to severe.
• Intermittent large bowel diarrhea often 
containing mucus and fresh blood 
(hematochezia).
• Bloody diarrhea with dehydration, anemia, 
and weight loss in severe cases.
• Signs can occur before eggs detectable in feces.
• Acute to chronic debilitation.
• Ingestion of infective (larvated) eggs from 
fecally contaminated environment.
• Eggs accumulate in environment and 
remain infective for months to years, 
especially in soil in moist, shady areas.
• Return of dog to an environment contami-
nated with infective eggs after anthelmintic 
treatment will result in reinfection.
  DIAGNOSIS
• Bacterial (spirochaetal) infections of cecum.
• Hookworm infection—identify eggs in feces; 
signs include anemia, pale mucous mem -
branes, melena rather than hematochezia.
• Gastrointestinal ulcers.
• Capillarid infections ( Pearsonema , 
Eucoleus )—eggs similar in appearance but 
smaller with roughened surface; infect urinary 
or respiratory tracts, respectively, rather than 
gastrointestinal tract; usually asymptomatic.
• Secondary pseudo-hypoadrenocorticism in 
severe trichuriasis with metabolic acidosis, 
hyponatremia, hyperkalemia, and dehydra-
tion; adrenocorticotropic hormone (ACTH) 
stimulation response is normal in cases of 
trichuriasis.CBC/BIOCHEMISTRY/URINALYSIS
Usually normal; hyponatremia, hyperkalemia, 
and metabolic acidosis can occur in severe 
cases.
ACTH stimulation test in severe cases with 
electrolyte disturbances to differentiate 
trichuriasis from hypoadrenocorticism.
IMAGING
N/A
• Centrifugal flotation of feces in sugar 
solution (specific gravity >1.2) preferred 
method.
• Differentiate Trichuris  eggs (brown, ovoid 
or lemon-shaped with prominent bipolar 
plugs, smooth shell, single cell within egg, 
~90 × 45 μm) from similar capillarid eggs 
(smaller, roughened shell surface).
• ELISA for whipworm antigen in feces—
commercial test detects antigen produced by 
male and female adult and immature worms, 
can detect prepatent infection; combine with 
microscopy as above.
  TREATMENT
• Outpatient treatment with anthelmintic for 
• Severe cases with dehydration and electrolyte 
disturbances require inpatient fluid therapy in 
addition to anthelmintic.
• Fenbendazole—50 mg/kg PO q24h for 
3 days; repeat monthly 3 times; extra-label 
in cats.
• Febantel/praziquantel/pyrantel pamoate—
label dose PO in dogs.
• Milbemycin oxime—0.5 mg/kg PO q30 
days in dogs.
• Moxidectin/imidacloprid—label dose in 
dogs.
  FOLLOW-UP
Repeat fecal examination for trichurid eggs 
and/or retreat with anthelmintic at 3 weeks 
and at 3 months following initial treatment 
or once a month for 3 months to detect and 
eliminate recently matured adults.
infective eggs.• Anthelmintic treatment of infected dogs to 
prevent shedding of eggs and contamination 
of environment.
Good prognosis following treatment and 
implementation of preventive measures.
Relatively rare cases of human infection with 
T. vulpis  have been diagnosed based on 
morphologic differences between eggs of the 
human whipworm, T. trichiura,  and those of 
T. vulpis .
Adolph C, Barnett S, Beall M, et al. 
Diagnostic strategies to reveal covert 
infections with intestinal helminths in 
dogs.Vet Parasitol 2017, 247(0):108–112.
Saunders, 2009, pp. 224–225.

1436  Blackwell’s Five-Minute Veterinary Consult  
XXylitol Toxicosis
 BASICS
OVERVIEW
• Xylitol—a 5-carbon sugar alcohol used 
most commonly as a sweetener; present in 
many sugar-free gums, candies, toothpastes, 
mouthwashes, chewable over-the-counter 
medications and supplements, nasal sprays, 
liquid medications, specialty foods, and baked 
goods. It is also available as a granulated 
powder for cooking and baking.
• Ingestion by dogs can cause vomiting, 
weakness, ataxia, seizures, hypokalemia, and 
hypoglycemia due to excess insulin release.
• Mild to moderate elevations of alanine 
aminotransferase (ALT) can be seen within  
4 hours of ingestion.
• Dosages >0.1 g/kg may cause hypo- 
glycemia.
• Hepatic failure may occur at dosages 
 >0.5 g/kg, with secondary coagulopathy 
possible due to hepatic necrosis.
• Dogs—no breed, age, or sex predilection.
• Cats—toxicity not expected.
SIGNS
• Vomiting may develop within 15–30 
minutes of exposure.
• Hypoglycemia may develop in as little as  
2 hours after ingestion, with signs including 
progressive lethargy, weakness, ataxia, 
collapse, and seizures.
• Hepatic failure with signs of icterus as well 
as possible hemorrhage including petechiae, 
ecchymosis, and gastrointestinal and 
abdominal bleeding may be seen within 
24–48 hours after ingestion.
• Hypoglycemia may not occur prior to onset 
of hepatic failure.
Ingestion of xylitol or xylitol-containing 
products.
 DIAGNOSIS
• Sulfonylurea antihyperglycemic agents.
• Insulinoma (pancreatic β-cell tumor).
Acute Hepatic Failure
• Acetaminophen.
• Sago palm ( Cycad  spp.).
• Aflatoxin.
• Amanita and similar hepatotoxic mushrooms.
• Iron.
• Leptospirosis.CBC/BIOCHEMISTRY/URINALYSIS
• Elevated ALT initially.
• Bilirubinemia.
• Elevated aspartate aminotransferase (AST), 
alkaline phosphatase (ALP) less consistent.
Prothrombin time/partial thromboplastin 
time (PT/PTT)—use if evidence of hepatic 
failure is present to monitor for development 
of secondary coagulopathy resulting in 
prolonged values.
N/A
• Severe acute periacinar and midzonal 
hepatic necrosis with periportal vacuolar 
• Petechiae and ecchymotic lesions suggestive 
of coagulation abnormalities.
 TREATMENT
• Decontamination—emesis up to 6 hours 
post ingestion is valid for gum exposures, if 
patient is asymptomatic; activated charcoal 
has poor binding to xylitol and not likely to 
• Monitor blood glucose every 2–4 hours for 
hypoglycemia and every 6–8 hours for hypo  - 
kalemia and correct as needed.
• Monitor liver enzymes every 12 hours for 
48 hours with ingestions >0.5 g/kg.
• Dextrose—0.5–1 g/kg IV followed by a 
2.5–5% CRI for hypoglycemia. Consider 
starting for ingestions >1 g/kg for hepato- 
protection.
• Potassium chloride—supplement in fluids 
if potassium value <2.5 mmol/L.
• N-Acetylcysteine—if hepatic enzyme 
elevations occur; or ingestions >1 g/kg; 
140 mg/kg PO or IV (extra-label) followed 
by 70 mg/kg every 6 hours for 7–17 doses, 
depending on the degree of hepatic enzyme 
changes.
• S-Adenosylmethionine (SAM-e)—PO daily 
for ingestions >0.5 g/kg. Administer for 2 
weeks if no to mild liver enzyme elevations 
occur and continue for 4 weeks if significant 
elevations occur.
None FOLLOW-UP
• Monitor glucose levels for at least 8–10 
hours.
• Monitor hepatic enzymes for 48 hours. If 
hepatic failure occurs, continue to monitor 
until values begin to decrease and again  
4 weeks post ingestion.
• Prognosis good for uncomplicated hypo  - 
glycemia with mild to moderate elevations of 
ALT; guarded to poor if severe hepatic 
necrosis occurs and early intervention is not 
• Patients who recover are not expected to 
have long-term negative effects.
SEE ALSO
• SAM-e = S-adenosylmethionine.
https://www.petpoisonhelpline.com/
uncategorized/xylitol-its-everywhere/
Jerzele A, Karancsi Z, Pászti-Gere E, et al. 
Effects of p.o. administered xylitol in cats. 
J Vet Pharmacol Ther 2018, 
41(3):409–414.
Schmid RD, Hovda LR. Acute hepatic failure 
in a dog after xylitol ingestion. J Med 
Toxicol 2016, 12(2):201–205.
acknowledge the prior contribution of Eric K. 
Dunayer.

Canine and Feline, Seventh Edition  1437
ZZinc Toxicosis
 BASICS
OVERVIEW
• Toxicity results from the ingestion of 
zinc-containing material. • Many zinc 
compounds: zinc carbonate and zinc 
gluconate (dietary supplements), zinc chloride 
(deodorants), zinc pyrithione (shampoos), 
zinc acetate (throat lozenges), zinc oxide 
(sunblock, Desitin, calamine lotion), zinc 
sulfide (paints), metallic zinc (coins).
• Causes gastrointestinal (GI) inflammation 
and intravascular hemolytic anemia; may 
cause multiple organ failure (e.g., renal, 
hepatic, pancreatic, and cardiac), dissemi-
nated intravascular coagulation (DIC), and 
cardiopulmonary arrest.
Most frequently reported in small-breed dogs 
less than 30 pounds (small pylorus retains 
zinc object or dose response); can occur in all 
species, all sizes.
SIGNS
• Onset of signs varies depending on the form 
of zinc, stomach acidity, and nutritional status 
of the patient. • Initial signs due to the irritant 
nature of the zinc chloride salts on the GI 
mucosa, causing vomiting, diarrhea, anorexia 
and lethargy. • Later signs associated with 
intravascular hemolysis and potential pancre -
atic, hepatic and renal damage; may include 
continued vomiting/diarrhea/anorexia, pale or 
icteric mucous membranes, dehydration, 
tachypnea, pigmenturia, abdominal discomfort, 
orange-tinged feces, melena.
• Toxic doses not well defined; unreferenced 
median lethal oral dose of “zinc salts” is 100 
mg/kg. • Toxicities result from ingestion of 
zinc-containing material: US pennies minted 
after 1982 (most common source), hardware 
(e.g., nuts, bolts), staples, galvanized metal 
(e.g., nails), boardgame pieces, zippers, toys, 
jewelry, holiday garland, bra clasps and hooks, 
animal identification tags, fixtures, buttons.
• Brass—alloy of copper and zinc. • Organic 
forms of zinc (e.g., zinc oxide) generally cause 
GI inflammation and self-limiting vomiting.
• Stomach acidity promotes rapid leaching of 
zinc from the ingested substance, allowing 
zinc to be absorbed.
 DIAGNOSIS
• GI upset—viral, bacterial, parasitic, 
immune-mediated, foreign body, liver or 
renal disease, pancreatitis. • Intravascular 
hemolysis—immune-mediated hemolytic anemia, Babesia , Allium  spp. (onion, garlic, 
chive, leek, shallot), copper, mothball 
toxicosis (naphthalene), caval syndrome, 
acetaminophen, coral snake venom, pit viper 
venom, brown recluse spider venom, 
mushrooms, overhydration, skunk spray, 
propylene glycol.
• Hemolytic anemia, with possible Heinz 
body formation (30% of cases)—PCV drops 
rapidly. • Regeneration will occur if enough 
time. • Target cells. • Spherocytosis—mild 
and often inconsistent (20% of cases).
• Hemoconcentration due to dehydration 
(prior to hemolysis). • Leukocytosis with 
neutrophilia. •  Hemoglobinemia.
• Bilirubinemia. • High AST, ALP; less 
common elevations in GGT and ALT.
• Elevated amylase and lipase. • Proteinuria, 
granular casts. • Pigmenturia. • Azotemia—
(prerenal or renal).
• Serum zinc levels often >5 ppm (normal 
dog/cat range: 0.70–2 ppm). Use non-zinc-
contaminated blood tubes for collection.
• Coagulation panel: may indicate DIC.
• Frequent monitoring of PCV.
IMAGING
• Abdominal imaging: may reveal metallic 
object(s) in the GI tract. • Often the zinc 
object has passed by the time the patient is 
admitted.
ECG—may reveal arrhythmias and 
ST-segment abnormalities.
 TREATMENT
• Rapid removal of the zinc object by 
endoscopy or laparotomy/gastrotomy.
• IV fluid therapy—maintain hydration and 
diuresis. • Severe intravascular hemolysis may 
require blood transfusion(s)/packed RBCs/ 
oxygen-carrying substances.
• Chelation therapy should not be warranted 
once the source of the zinc is removed. Zinc 
levels drop fairly rapidly (few to several days) 
via excretion into bile, pancreatic secretions, 
and urine. • CaEDTA 100 mg/kg diluted in 
5% dextrose SC, divided into 4 doses per day 
(as for lead poisoning) if clinical improve-
ment or reduced serum zinc is not accom-
plished by removal of zinc objects. Not 
commonly used and is potentially nephro-
toxic. • Penicillamine 110 mg/kg/day PO q6–8h for 5–14 days (as for lead poisoning) if 
clinical improvement or reduced serum zinc is 
not accomplished by removal of zinc objects. 
Safer chelator to use. • Heparin 150 U/kg SC 
q6h, for DIC. • H2-receptor antagonists (e.g., 
cimetidine, ranitidine, famotidine), proton 
pump inhibitors (e.g., omeprazole), sucral-
fate, and antacids used alone or in combina-
tion may help reduce irritation and stomach 
acidity and the rate of release and absorption 
of zinc.
Avoid aminoglycoside antibiotics and other 
potential nephrotoxins due to added risk of 
developing acute renal failure.
 FOLLOW-UP
• ECG—monitor for evidence of arrhyth-
mias, ST-segment alterations. • Coagulation 
profile, PCV, RBC, amylase, lipase, BUN, 
creatinine, ALP , AST, and ALT—monitor for 
the first 72 hours after removal of zinc source. 
• Monitor serum zinc levels.
Educate clients on zinc hazards.
• Multiple organ failure (e.g., kidney, 
liver), DIC, pancreatic disease, cardiopul -
monary arrest are not common but 
potential outcomes. • Rapid removal of 
zinc source may provide progressive 
improvement over 48–72 hours; complete 
recovery possible.
aminotransferase. • DIC = disseminated 
intravascular coagulation. • GGT = gamma-
glutamyltransferase. • GI = gastrointestinal.
• PCV = packed cell volume. • PT = 
prothrombin time. • PTT = partial thrombo-
plastin time. • RBC = red blood cells.
Lee YR, Kang MH, Park HM. T reatment of 
zinc toxicosis in a dog with chelation using 
d-penicillamine. J Vet Emerg Crit Care 
2016, 26(6):825–830.
Talcott PA. Zinc poisoning. In: Peterson ME, 
2013, pp. 847–851.
Author  Patricia A. Talcott

Appendices
 Appendix I  Normal Reference Ranges for Laboratory Tests  1441
 Table I-A  Normal hematologic values  1441
 Table I-B  Normal biochemical values  1441
 Table I-C  Conversion table for hematologic units  1442
 Table I-D  Conversion table for clinical biochemical units  1443
 Appendix II  Endocrine Testing  1444
 Table II-A  Endocrine function testing protocols  1444
 Table II-B  Tests of the endocrine system  1445
 Table II-C  Conversion table for hormone assay units  1446
 Appendix III  Approximate Normal Ranges for Common Measurements in Dogs and Cats  1447
 Appendix IV  Normal Values for the Canine and Feline Electrocardiogram  1448
 Appendix V  Antidotes and Useful Drugs: Methods of Treatment  1449
 Appendix VI  Toxic Home and Garden Hazards for Pets  1452
 Table VI-A  Toxic plants and their clinical signs—antidotes and treatment  1452
 Table VI-B  Herbal toxicities  1457
 Table VI-C  Household cleaners, disinfectants, and solvents—products, clinical signs, and treatment  1460
 Appendix VII  Pain Management  1465
 Table VII-A  Recommended parenteral opioid dosages and indications  1465
 Table VII-B  Recommended dispensable opioid dosages and indications  1465
 Table VII-C  Recommended parenteral local anesthetic dosages and indications  1466
 Table VII-D  Recommended parenteral NSAID dosages and indications  1466
 Table VII-E  Recommended dispensable NSAID dosages and indications  1467
 Table VII-F  Dosages and indications for selected drugs used to treat neuropathic pain  1468
 Appendix VIII  Medications and Supplements for Osteoarthritis  1469
 Table VIII-A  Anti-inflammatories and pain medications  1469
 Table VIII-B  Recommended parenteral NSAID dosages and indications  1470
 Table VIII-C  Recommended oral NSAID dosages and indications  1471
 Table VIII-D  Disease-Modifying Drugs (DMOADs)  1472
 Appendix IX  Glossary of Terminology for Seizures and Epileptic Disorders  1473
 Appendix X  Common Procedures and Testing Protocols  1475
  Abdominocentesis and Fluid Analysis  1476
  Arthrocentesis With Synovial Fluid Analysis  1479
  Bacterial Culture and Sensitivity  1483
  Blood Gas Interpretation  1485
  Blood Pressure Determination: Noninvasive and Invasive  1488
  Blood Sample Collection  1490
  Blood Smear Microscopic Examination  1492
  Blood Smear Preparation  1496
  Blood Typing  1498
  Bone Marrow Aspirate and Biopsy  1501
  Bone Marrow Aspirate Cytology: Microscopic Evaluation  1503
  Complete Ophthalmologic Exam  1507
  Crossmatch  1512
  Cystocentesis  1514
  Electrocardiography  1517
  Fecal Direct Smear and Cytology  1520
  Fecal Flotation  1522
  Fine-Needle Aspiration  1525
  Fluid Analysis  1527
  Glucose Curve  1530
  Impression Smear  1533
1439

1440  Blackwell’s Five-Minute Veterinary Consult  
  Pericardiocentesis  1534
  Point of Care Abdominal Ultrasonography  1538
  Point of Care Pleural Space and Lung Ultrasonography  1541
  Rectal Scraping and Cytology  1547
  Saline Agglutination Test  1548
  Thoracocentesis and Fluid Analysis  1550
  T racheal Wash  1553
  Ultrasound-Guided Mass or Organ Aspiration  1555
  Urethral Catheterization  1559
  Urinalysis Overview  1563
  Urine Sediment  1565
 Appendix XI  Conversion Tables  1569
 Table XI-A  Conversion table of weight to body surface area (in square meters) for dogs  1569
 Table XI-B  Approximate equivalents for degrees Fahrenheit and Celsius  1569
 Table XI-C  Weight-unit conversion factors  1570
 Appendix XII  Important Resources for Veterinarians  1571

Canine and Feline, Seventh Edition  1441
Normal Reference Ranges for Laboratory TestsAppendix I
Table I-A
Normal hematologic values
T est Units Dogs Cats
WBC 10 × 3/mm36.0–17.0 5.5–19.5
RBC 10 × 6/mm35.5–8.5 6.0–10
Hemoglobin g/dL 12.0–18.0 9.5–15
Hematocrit % 37.0–55.0 29–45
Mean corpuscular volume fL 60.0–77.0 41.0–54
Mean corpuscular hemoglobin pg 19.5–26 13.3–17.5
Mean corpuscular hemoglobin concentration % 32.0–36.0 31–36
Platelet count (automated) 10 × 3/mm3200–500 150–600
Platelet count (manual) 10 × 3/mm3164–510 230–680
Neutrophils % 60–77 35–75
Absolute 3,000–11,500 2,500–12,500
Bands % 0–3 0–3
Absolute 0–510 0–585
Lymphocytes % 12–30 20–55
Absolute 1,000–4,800 1,500–7,000
Monocytes % 3–10 1–4
Absolute 180–1,350 0–850
Eosinophils % 2–10 2–12
Absolute 1,000–1,250 0–1,500
Basophils % 0–1 0–1
Absolute 0–100 0–100
Reticulocyte count % 0.5–1.5 0.0–1.0
Corrected % 0.0–1.0 0.0–1.0
Absolute /mm30–80,000 0–50,000
Source: Adapted from Abbott Cell Dyne 3500; IDEXX Veterinary Services.
It is important to realize that normal values vary among individual laboratories.
Table I-B
Normal biochemical values
Blood urea nitrogen (BUN) mg/dL 7–27 15–34
Creatinine mg/dL 0.4–1.8 0.8–2.3
Cholesterol mg/dL 112–328 82–218
Glucose mg/dL 60–125 70–150
Alkaline phosphatase (ALP) IU/L 10–150 0–62
Alanine aminotransferase (ALT) IU/L 5–60 28–76
Aspartate aminotransferase (AST) IU/L 5–55 5–55
Total protein g/dL 5.1–7.8 5.9–8.5
Albumin g/dL 2.6–4.3 2.4–4.1
Globulin g/dL 2.3–4.5 3.4–5.2
Albumin–globulin ratio 0.75–1.9 0.6–1.5
Sodium mEq/L 141–156 147–156
Potassium mEq/L 4.0–5.6 3.9–5.3
Sodium–potassium ratio 27–40 > 27.0
Chloride mEq/L 105–115 111–125

1442  Blackwell’s Five-Minute Veterinary Consult  
Total CO2mEq/L 17–24 13–25
Anion gap mEq/L 12–24 13–27
Calcium mg/dL 7.5–11.3 7.5–10.8
Phosphorus mg/dL 2.1–6.3 3.0–7.0
Total bilirubin mg/dL 0–0.4 0.0–0.4
Direct bilirubin mg/dL 0.0–0.1 0.0–0.1
Indirect bilirubin mg/dL 0–0.3 0.0–0.3
Lactate dehydrogenase (LDH) IU/L 50–380 46–350
Creatine kinase (CK or CPK) IU/L 10–200 64–440
Gamma glutamyl transferase (GGT) IU/L 0–10 1–7
Uric acid mg/dL 0–2 0–1
Amylase IU/L 500–1,500 500–1,500
Lipase U/L 100–500 10–195
Magnesium mEq/L 1.8–2.4 1.8–2.4
Triglycerides mg/dL 20–150 20–90
Bile acids:
Fasting μmol/L 0.0–5.0 0.0–5.0
Post-prandial μmol/L < 25 < 15
Random μmol/L < 25 < 15
Total iron μwg/dL 33–147 33–134
Unsaturated iron binding capacity μwg/dL 127–340 105–205
Total iron binding capacity μwg/dL 282–386 169–325
Source: Adapted from Hitachi Chemistry Analyzer model 747 IDEXX Veterinary Services.
It is important to realize that normal values vary among individual laboratories.Table I-B
Normal biochemical values ( continued )
Table I-C
Conversion table for hematologic units
Example Values Conversion Factors
Analyte Traditional SI* Traditional to SI SI to Traditional
Hemoglobin 15.0 g/dL 150 g/L 10 0.1
HCT or PCV 45% 0.45 L/L 0.01 100
Erythrocytes 6.0 × 106/mm36.0 × 1012/L 10610–6
MCV 75 μ375 fL No change No change
MCH 25 μg 25 pg No change No change
MCHC 33 g/dL 330 g/L 10 0.1
WBC 15.0 × 103/mm315.0 × 109/L 10610–6
Platelets 250 × 103/mm3250 × 109/L 10610–6
* Système International d’Unites.
Modified from Appendices. In: BonaguraJD, ed., Kirk’s Current Veterinary Therapy XIII. Philadelphia: 
Saunders, 2000, p. 1209.Normal Reference Ranges for Laboratory Tests ( continued )

Canine and Feline, Seventh Edition  1443
Table I-D
Conversion table for clinical biochemical units
Analyte Traditional Unit (with Examples) Conversion Factor SI Unit (with Examples)
Alanine aminotransferase 0–40 U/L 1.00 0–40 U/L
Albumin 2.8–4.0 g/dL 10.0 28–40 g/L
Alkaline phosphatase 30–150 U/L 1.00 30–150 U/L
Ammonia 10–80 μg/dL 0.5871 5.9–47.0 μmol/L
Amylase 200–800 U/L 1.00 200–800 U/L
Aspartate aminotransferase 0–40 U/L 1.00 0–40 U/L
Bile acids (total) 0.3–2.3 μg/mL 2.45 0.74–5.64 μmol/L
Bilirubin 0.1–0.2 mg/dL 17.10 2–4 μmol/L
Calcium 8.8–10.3 mg/dL 0.2495 2.20–2.58 mmol/L
Carbon dioxide 22–28 mEq/L 1.00 22–28 mmol/L
Chloride 95–100 mEq/L 1.00 95–100 mmol/L
Cholesterol 100–265 mg/dL 0.0258 2.58–5.85 mmol/L
Copper 70–140 μg/dL 0.1574 11.0–22.0 μmol/L
Cortisol 2–10 μg/dL 27.59 55–280 nmol/L
Creatine kinase 0–130 U/L 1.00 0–130 U/L
Creatinine 0.6–1.2 mg/dL 88.40 50–110 μmol/L
Fibrinogen 200–400 mg/dL 0.01 2.0–4.0 g/L
Folic acid 3.5–11.0 μg/L 2.265 7.93–24.92 nmol/L
Glucose 70–110 mg/dL 0.05551 3.9–6.1 mmol/L
Iron 80–180 μg/dL 0.1791 14–32 μmol/L
Lactate 5–20 mg/dL 0.1110 0.5–2.0 mmol/L
Lead 150 μg/dL 0.04826 7.2 μmol/L
Lipase, Sigma-Tietz (37ºC) ≤ 1 ST U/dL 280 ≤ 280 U/L
Lipase, Cherry-Crandall (30ºC) 0–160 U/L 1.00 0–160 U/L
Lipids (total) 400–850 mg/dL 0.01 4.0–8.5 g/L
Magnesium 1.8–3.0 mg/dL 0.4114 0.80–1.20 mmol/L
Mercury ≥ 1.0 μg/dL 49.85 ≤ 50 nmol/L
Osmolality 280–300 mOsm/kg 1.00 280–300 mmol/kg
Phosphorus 2.5–5.0 mg/dL 0.3229 0.80–1.6 mmol/L
Potassium 3.5–5.0 mEq/L 1.0 3.5–5.0 mmol/L
Protein (total) 5–8 g/dL 10.0 50–80 g/L
Sodium 135–147 mEq/L 1.00 135–147 mmol/L
Testosterone 4.0–8.0 mg/mL 3.467 14.0–28.0 nmol/L
Thyroxine 1–4 μg/dL 12.87 13–51 nmol/L
Triglyceride 10–500 mg/dL 0.0113 0.11–5.65 mmol/L
Urea nitrogen 10–20 mg/dL 0.3570 3.6–7.1 nmol/L
Uric acid 3.6–7.7 mg/dL 59.44 214–458 μmol/L
Urobilinogen 0–4.0 mg/dL 16.9 0.0–6.8 μmol/L
Vitamin A 90 μg/dL 0.03491 3.1 μmol/L
Vitamin B12 300–700 ng/L 0.738 221–516 pmol/L
Vitamin E 5.0–20.0 mg/L 2.32 11.6–46.4 μmol/L
D–xylose 30–40 mg/dL 0.06666 2.0–2.71 mmol/L
Zinc 75–120 μg/dL 0.1530 11.5–18.5 μmol/L
Source: Adapted from Appendices. In: Bonagura JD, ed., Kirk’s Current Veterinary Therapy XIII. Philadelphia: Saunders, 2000, p. 1214.Normal Reference Ranges for Laboratory Tests ( continued )

1444  Blackwell’s Five-Minute Veterinary Consult  
Endocrine Testing
 Table II-A
Endocrine function testing protocols
ADRENAL GLAND 
DISORDERS
ACTH STIMULATION TEST
Screening for Hyperadrenocorticism 
(in dogs; test not recommended 
for diagnosis of HAC in cats)
• Administer 5 μg/kg (up to 250 μg/dog) 
synthetic ACTH (cosyntropin; Cortrosyn, 
Organon Pharmaceuticals, West Orange, NJ), 
IV or IM. Serum samples should be obtained 
before and 1 hour after injection of ACTH for 
cortisol assay.
• Alternatively, but less ideal, 2.2 IU/kg 
ACTH gel may be given IM, and serum 
samples obtained before and 1 and 2 hours 
post injection.
Interpretation
An exaggerated response to ACTH is 
consistent with Cushing’s disease. High normal 
cut-off values differ slightly between 
laboratories.
Screening for hypoadrenocorticism
• Administer 1 μg/kg (dogs) or 5 μg/kg (cats) 
cosyntropin, IV. Serum samples should be 
obtained before and 1 hour after injection of 
ACTH for cortisol assay.
• The use of ACTH gel for the diagnosis of 
Addison’s is not recommended.
Pre- and post-cortisol determinations <2 μg/dL 
(55 nmol/L) are consistent with 
Monitoring mitotane and trilostane 
administration in dogs
• Test should be started 3–4 hours after 
administration of trilostane.
• Monitoring mitotane therapy for 
hyperadrenocorticism: Pre- and post-cortisol 
values are between 1 and 5 μg/dL.
• Monitoring trilostane therapy for 
hyperadrenocorticism: Post-ACTH cortisol 
values between 2 and 6 μg/dL are 
acceptable, but this range is controversial. 
Results must be interpreted in light of 
clinical signs.LOW-DOSE DEXAMETHASONE 
SUPPRESSION TEST (LDDST)
Dogs
Administer 0.01 mg/kg dexamethasone IV. 
Obtain serum samples before and 4 and 8 hours 
after injection of dexamethasone for cortisol assay.
Cats
Administer 0.1 mg/kg dexamethasone IV. Obtain 
serum sample before and 4 and 8 hours after 
injection of dexamethasone for cortisol assay.
Three basic patterns:
• Lack of suppression: All cortisol values 
remain above 1.4 μg/dL (40 nmol/L). This 
pattern is consistent with Cushing’s disease.
• Suppression: Cortisol values fall below 1.4 μg/dL 
(40 nmol/L) at 4 and 8 hours. This pattern suggests 
that the animal does not have Cushing’s disease.
• Escape from suppression: Cortisol value falls 
below 1.4 μg/dL (40 nmol/L) at 4 hours and 
rises above 1.4 μg/dL at 8 hours. This pattern 
is consistent with pituitary-dependent 
Cushing’s disease.
HIGH-DOSE DEXAMETHASONE 
SUPPRESSION TEST (HDDST)
serum samples before and 4 and 8 hours after 
Any cortisol determination that falls below 
1.4 μg/dL (40 nmol/L) at any point during the 
8-hour testing period is considered suppression. 
Suppression after a high dose of dexamethasone 
Cushing’s disease. Lack of suppression (all 
cortisol values remain above 1.4 μg/dL) is 
diagnostic of a pituitary or adrenal tumor.
 THYROID GLAND DISORDERS
TSH STIMULATION TEST
Administer 0.5 U/kg TSH (maximum dose 5 
U) IV. Obtain serum samples before and 6 
hours after injection of TSH for T4 
determination.
Post-TSH T4 levels <3 μg/dL (35 nmol/L) are 
consistent with hypothyroidism.
TRH STIMULATION TEST
Administer 0.1 mg/kg TRH IV. Obtain serum 
samples before and 4 hours after TRH 
injection for T4 determination.Interpretation
An increase in T4 concentration <50% after 
TRH administration is consistent with 
T3 SUPPRESSION TEST
Obtain a blood sample for determination of T4 
and T3. The serum is removed and kept 
refrigerated or frozen. Administer T3 (Cytomel, 
SmithKline Beecham, Philadelphia, PA) PO at 
a dosage of 25 μg/cat q8h for 2 days. On the 
morning of the third day, administer 25 μg of 
T3, and 2–4 hours later obtain a second blood 
sample for T3 and T4 determinations. The basal 
(day 1) and post-oral T3 serum samples should 
be submitted to the laboratory together to 
avoid interassay variation.
Serum T4 concentration after administration of 
T3 >1.5 μg/dL (20 nmol/L) is consistent with 
 SEX HORMONE DISORDERS
GNRH STIMULATION TEST
Administer 0.5–1.0 μg of GnRH/kg IM. 
Obtain blood samples before GnRH 
administration and 1 hour later. Assay blood 
samples for testosterone.
Normal dogs have baseline testosterone levels 
between 0.5 and 5 ng/mL, and after 
administration of GnRH the testosterone levels 
rise above 5 ng/mL. Animals with 
hypoandrogenism have lower values.
HCG STIMULATION TEST
Administer 44 IU of hCG/kg IM. Obtain 
blood samples before hCG administration and 
4 hours later. Assay blood samples for 
administration of hCG, the testosterone levels 
 DIABETES INSIPIDUS
MODIFIED WATER DEPRIVATION TEST
Note: This is not recommended due to 
morbidity and potential complications; ADH 
supplementation trial preferred.
Rule out other causes of polyuria and 
polydipsia (especially hyperadrenocorticism). Appendix II

Canine and Feline, Seventh Edition  1445
Table II-B
Tests of the endocrine system*
† Unit Dogs Cats
Adrenocorticotropic hormone, basal (ACTH, plasma) pmol/L 2–15 1–20
Aldosterone† (plasma)
Basal pmol/L 14–957 194–388
Post-ACTH pmol/L 197–2103 277–721
Cortisol (serum or plasma, urine)
Basal nmol/L 25–125 15–150
Post-ACTH nmol/L 200–550 130–450
Post–low-dose dexamethasone (0.01 or 0.015 mg/kg) nmol/L ≤ 40 ≤ 40
Post–high-dose dexamethasone (0.1 or 1.0 mg/kg)‡nmol/L ≤ 40 ≤ 40
Urinary cortisol-creatinine ratio × 10–68–24,† 10§—
Insulin, basal (serum) pmol/L 35–200 35–200
Intact parathormone† (serum) pmol/L 2–13 0–4
Progesterone (serum or plasma, female) mmol/L ≤ 3.0 in anestrus, proestrus ≤ 3.0 in anestrus, proestrus
50–220 in diestrus, pregnancy 50–220 in diestrus, pregnancy
Testosterone (serum or plasma, male) nmol/L 1–20 1–20
Thyroxine (T4, serum)
Basal nmol/L 12–50 10–50
Post–thyroxine-stimulating hormone (TSH) nmol/L > 45 > 45
Triiodothyronine (T3) suppression* nmol/L — ≤ 20
Triiodothyronine, basal (T3, serum) nmol/L 0.7–2.3 0.5–2.0
* Prepared with the assistance of ME Peterson, The Animal Medical Center, New York, NY. Unless indicated otherwise, values in this table are adapted from Kemppainen 
RJ, Zerbe CA. Common endocrine diagnostic tests: normal values and interpretations. In: Kirk RW, ed., Current Veterinary Therapy X. Philadelphia: Saunders, 1989, 
pp. 961–968. Hormone determinations are variable between laboratories. The laboratory performing the analysis should provide reference values. Before submitting 
samples for hormone determinations, consult the laboratory for sample specifications, use of anticoagulants, and sample preservation. General sampling conditions are 
discussed in Reimers TJ. Guidelines for collection, storage, and transport of samples for hormone assay. In: Kirk RW, ed., Current Veterinary Therapy X. Philadelphia: 
Saunders, 1989, pp. 968–973. Factors that affect serum thyroid and adrenocortical hormone concentrations in dogs are discussed in Reimers TJ, Lawler DF , Sutaria PM, 
et al. Effects of age, sex, and body size on serum concentrations of thyroid and adrenocortical hormones in dogs. Am J Vet Res 1990, 51:454.
† Provided by RF Nachreiner, Animal Health Diagnostic Laboratory, Endocrine Diagnostic Section, Michigan State University.
‡ This test is used after adrenocortical hyperfunction has been confirmed. It is used to differentiate adrenal tumor (where no suppression is seen) from pituitary-
dependent cases (where suppression occurs but is variable).
§ From Stolp R, Rijnberk A, Meiher JC, Croughs RJM. Urinary corticoids in the diagnosis of canine hyperadrenocorticism. Res Vet Sci 1983, 34:141.
Rijnberk A, van Wees A, Mol JA. Assessment of two tests for the diagnosis of canine hyperadrenocorticism. Vet Record 1988, 122:178–180.
* From Peterson ME, Ferguson DC. Thyroid diseases. In: Ettinger SJ, ed., Textbook of Veterinary Internal Medicine: Diseases of the Dog and Cat, 3rded. Philadelphia: 
Saunders, 1989, pp. 1632–1675.
From Appendices. In: Bonagura JD, ed., Kirk’s Current Veterinary Therapy XIII. Philadelphia: Saunders, 2000, p. 1223.Begin water restriction 3 days before abrupt 
water deprivation.
• Day 1: 130–165 mL/kg/day.
• Day 2: 100–125 mL/kg/day.
• Day 3: 65–70 mL/kg/day (normal 
maintenance requirement).
The morning of the fourth day, discontinue 
food and water. Start the test. Weigh the patient 
and empty the bladder. Weigh and measure 
PCV/TP , USG, BUN, and Na+ at 1- to 2-hour 
intervals. Monitor carefully for dehydration and 
depression and discontinue the test if the patient becomes dull, azotemic, or hypernatremic . When 
5% of body weight is lost (or azotemia, 
hypernatremia, or dullness develop), empty the 
bladder and check urine specific gravity.
If the urine specific gravity is >1.025 (dogs) or 
>1.030 (cats), stop the test. The patient does 
not have diabetes insipidus. If the urine specific 
gravity is not >1.025 (dogs) or >1.030 (cats), 
administer 0.55 U/kg aqueous vasopressin IM 
(maximum dose 5 U). Empty the bladder and 
check urine specific gravity at 30, 60, and 120 minutes post administration. If urine specific 
gravity increases <10%, nephrogenic diabetes 
insipidus is indicated; if it increases 10–50%, 
partial central diabetes insipidus is indicated; if 
it increases 50–800%, complete central diabetes 
insipidus is indicated.
DDAVP (desmopressin), 5 μg/dog SQ may 
be used in place of aqueous vasopressin, with 
specific gravity assessed at 2 and 4 hours.
Following the test, water should be offered in 
small amounts initially (to avoid vomiting), and 
slowly increased back to the dog’s daily intake.Endocrine Testing ( continued )
 Table II-A
Endocrine function testing protocols ( continued )

1446  Blackwell’s Five-Minute Veterinary Consult  
Table II-C
Conversion table for hormone assay units
Unit Conversion Factors
Hormone Traditional SI Traditional to SI SI to Traditional
Aldosterone ng/dL pmol/L 27.7 0.036
Corticotropin (ACTH) pg/mL pmol/L 0.22 4.51
Cortisol μg/dL mmol/L 27.59 0.36
β-endorphin pg/mL pmol/L 0.289 3.43
Epinephrine pg/mL pmol/L 5.46 0.183
Estrogen (estradiol) pg/mL pmol/L 3.67 0.273
Gastrin pg/mL ng/L 1.00 1.00
Glucagon pg/mL ng/L 1.00 1.00
Growth hormone (GH) ng/mL μg/L 1.00 1.00
Insulin μU/mL pmol/L 7.18 0.139
α-melanocyte-stimulating hormone ( α-MSH) pg/mL pmol/L 0.601 1.66
Norepinephrine pg/mL nmol/L 0.006 169
Pancreatic polypeptide (PP) mg/dL mmol/L 0.239 4.18
Progesterone ng/mL mmol/L 3.18 0.315
Prolactin ng/mL μg/L 1.00 1.00
Renin ng/mL/hr ng/L/sec 0.278 3.60
Somatostatin pg/mL pmol/L 0.611 1.64
Testosterone ng/mL nmol/L 3.47 0.288
Thyroxine (T4) μg/dL nmol/L 12.87 0.078
Triiodothyronine (T3) ng/dL nmol/L 0.0154 64.9
Vasoactive intestinal polypeptide (VIP) pg/mL pmol/L 0.301 3.33
Sources: Contributed by ME Peterson, The Animal Medical Center, New York, NY.
From Appendices. In: Bonagura JD, ed., Kirk’s Current Veterinary Therapy XIII. Philadelphia: Saunders, 2000, p. 1223.Endocrine Testing ( continued )

Canine and Feline, Seventh Edition  1447
Approximate Normal Ranges for Common Measurements in Dogs and CatsAppendix III
Dog Cat
Heart rate (bpm) 60–180 140–220
Capillary refill time 1.5–2 sec 1.5–2 sec
Body temperature 99.5–102.5°F 100.5–102.5ºF
37.5–39.2°C 38.1–39.2ºC
Mean arterial pressure (mm Hg) 90–120 100–150
Blood volume (mL/kg) 75–90 47–66
Cardiac output
(mL/kg/min) 100–200 167 ± 39
(L/M2/min) 4.72 ± 1.09
Systemic vascular resistance
(mm Hg/mL/kg/min) 1600–2500 dynes.sec.cm−5
(dynes/sec/cm) 2162 ± 458
Mean pulmonary arterial pressure (mm Hg) 14±3
Central venous pressure (cm H2O) 3±4
Urine output 1–2 mL/kg/hr 1–2 mL/kg/hr
Breathing rate (breaths/min) 10–30 24–42
Minute ventilation (mL/kg/min) 170–350 200–350
Oxygen delivery
(mL/kg/min) 29 ± 8
(mL/M2/min) 815 ± 234
Oxygen consumption
(mL/kg/min) 4–11 3–8
(mL/M2/min) 198 ± 53
Arterial Po2 (mm Hg) 85–105 100–115
Arterial So2> 95 > 95
Arterial Pco2 (mm Hg) 30–44 28–35
Arterial pH 7.36–7.46 7.34–7.43
Bicarbonate (mEq/L) 20–25 17–21
Base deficit (mEq/L) 0 to –4 –1 to –8
Total plasma proteins (g/dL) 6.0–8.0 6.8–8.3
Albumin (g/dL) 2.5–3.5 2.4–3.8
Packed cell volume (%) 37–55 29–48
Hemoglobin (g/dL) 12–18 9–15.1
Sodium (mEq/L) 145–154 146–157
Potassium (mEq/L) 3.9–4.9 3.6–4.9
Chloride (mEq/L) 105–116 113–121
Total CO2 (mEq/L) 16–26 15–21
Source: Modified from Aldrich J, Haskins SC. Monitoring the critically ill patient. In: Current Veterinary Therapy XII.  
Philadelphia: Saunders, 1995, pp. 98–105.

1448  Blackwell’s Five-Minute Veterinary Consult  
Rate
Dog 60–140 beats/min for giant breeds
70–160 beats/min for adult dogs
Up to 180 beats/min for toy breeds
Up to 220 beats/min for puppies
Cat Range: 120–240 beats/min
Mean: 197 beats/min
Rhythm
Dog Normal sinus rhythm
Sinus arrhythmia
Wandering sinoatrial pacemaker
Cat Normal sinus rhythm
Sinus tachycardia (physiologic reaction to excitement)
Measurements (lead II, 50 mm/sec, 1 cm = 1 mV)
Dog P wave Width: maximum, 0.04 second; 0.05 second in giant breeds
Height: maximum, 0.4 mV
PR interval Width: 0.06–0.13 second
QRS complex Width: maximum, 0.05 second in small breeds
maximum, 0.06 second in large breeds
Height of R wave*: maximum, 3.0 mV in large breeds
maximum, 2.5 mV in small breeds
ST segment No depression: not more than 0.2 mV
No elevation: not more than 0.15 mV
T wave Can be positive, negative, or biphasic
Not greater than one-fourth amplitude of R wave
Amplitude range ± 0.05–1.0 mV in any lead
Q-T interval Width: 0.15–0.25 second at normal heart rate; varies with heart rate (faster rates have shorter Q-T 
intervals and vice versa)
Cat P wave Width: maximum, 0.04 second
Height: maximum, 0.2 mV
PR interval Width: 0.05–0.09 second
QRS complex Width: maximum, 0.04 second
Height of R wave: maximum, 0.9 mV
ST segment No depression or elevation
T wave Can be positive, negative, or biphasic—most often positive
Maximum amplitude: 0.3 mV
Q-T interval Width: 0.12–0.18 second at normal heart rate (range 0.07–0.20 second); varies with heart rate (faster 
rates have shorter Q-T intervals and vice versa)
Mean Electrical Axis (frontal plane)
Dog +40 to +100 degrees
Cat 0 to + 160 degrees (not valid in many cats)
Precordial Chest Leads (values of special importance)
Dog CV5RL (rV2): T wave positive, R wave not greater than 3.0 mV
CV6LL (V2): S wave not greater than 0.8 mV, R wave not greater than 3.0 mV*
CV6LU (V4): S wave not greater than 0.7 mV, R wave not greater than 3.0 mV*
V10: negative QRS complex, T wave negative except in Chihuahuas
Cat CV6LL (V2): R wave not greater than 1.0 mV
CV6LU (V4): R wave not greater than 1.0 mV
V10: T wave negative, R/Q not greater than 1.0 mV
* Not valid for thin, deep-chested dogs under 2 years of age.
Source: From Tilley LP . Essentials of Canine and Feline Electrocardiography, 3rd ed. Baltimore: Williams & Wilkins, 1992, Reprinted with permission of Wolters Kluwer.Normal Values for the Canine and Feline ElectrocardiogramAppendix IV

Canine and Feline, Seventh Edition  1449
Antidotes and Useful Drugs: Methods of TreatmentAppendix V
Antidotes and Useful 
Drugs Toxicant/Indication for Use Dosage
Acepromazine Amphetamine and other stimulant drugs 
with agitation and excitation; serotonin 
syndromeDogs and cats: 0.02–0.1 mg/kg IV, IM, SC. May cause hypotension.
Antivenin, crotalids Crotalus  and Sistrurus  (rattlesnake); 
Agkistrodon  (cottonmouth and 
copperhead) venomSeveral products available. Follow the manufacturer’s guidelines for 
dilution and administration. Dose varies from 1 to 5 vials IV depending 
on severity of symptoms. 95% of cases controlled with a single vial.
Antivenin, elapids Micrurus fulvius, Micrurus tenere, Micruroides 
euryxanthus  (coral snakes) venomExtremely limited availability. The manufacturer’s guidelines for dilution 
and administration should be followed closely.
Atipamezole Medetomidine, dexmedetomidine reversal. 
Used off-label to reverse other 
alpha-2-adrenergic agonists, including 
amitraz, clonidine, and xylazineDogs: 50–100 μg/kg IM
Cats: 25–50 μg/kg IM or IV (slow)
Atropine Anticholinesterase pesticide muscarinic 
signs (OPs and carbamates); also 
cholinergic agents and clitocybe and 
inocybe (muscarinic) mushroomsDogs and cats: 0.2–2 mg/kg. One quarter of the dose should be given IV 
and the remainder IM or SC. The dose will likely need to be repeated; 
heart rate and secretions should be used to guide redosing.
Barbiturates Strychnine and other seizure-producing 
drugsDogs: Phenobarbital at 5–8 mg/kg IV q4–6h.
Cats: Phenobarbital at 3 mg/kg IV, repeat every 20 minutes to maximum 
of 24 mg/kg/24 hours.
Calcitonin salmon Hypercalcemia; vitamin D and analogs 4–6 IU/kg, SC q8–12h. Rarely used.
Calcium gluconate or 
chlorideFluoride and hydrofluoric acid; oxalic acid 
and oxalates; beta and calcium channel 
antagonists; othersCalcium gluconate 10% 0.54–1.61 mL/kg IV slowly; calcium chloride 
10% 0.18–0.56 mL/kg IV slowly.
Calcium disodium 
EDTA (CaEDTA or 
calcium disodium 
versenate)Heavy metals, primarily lead and zinc. Also 
chelates cadmium, chromium, copper, 
cobalt, iron, manganese, nickel, plutonium, 
thorium, uranium, yttrium, and vanadiumDilute product in 5% dextrose to a final concentration of 2–4 mg/mL 
prior to use. Give 25 mg/kg IV or SC q6h. Maximum recommended 
daily dose of 2 g/day. Treat for 5 days; rest for 5–7 days; and repeat if 
needed. Do not use if metal still present in GIT.
Cyproheptadine Drugs that cause serotonin syndrome 
(selective serotonin reuptake inhibitors, 
tricyclic antidepressants, 
5-hydroxytryptophan)Dogs: 1.1 mg/kg PO or rectally q4–8h PRN.
Cats: 2–4 mg total dose PO or rectally q4–8h PRN.
D-penicillamine Heavy metals, primarily lead; but also 
cadmium, copper, inorganic mercury, 
and zincDogs (home therapy after CaNa2EDTA lead treatment): 110 mg/kg/day 
PO divided q6–8h for 1–2 weeks.
Cats (home therapy after CaNa2EDTA lead treatment and in the presence 
of elevated blood levels): 125 mg total dose, PO q12h for 5 days.
Do not use if metal still present in GI tract.
Dantrolene Hops (Humulus lupulus)  intoxication and 
black widow spider envenomation 
(Latrodectus mactans )Dogs: Black widow spider: 1 mg/kg IV followed by 1 mg/kg PO q4h as 
needed.
Hops: 2–3 mg/kg IV or 3.5 mg/kg PO.
Deferoxamine Iron Dogs and cats: 40 mg/kg IM q4–8h. In critical situations, an IV infusion of 
15 mg/kg/hour can be used, but the cardiovascular system must be 
monitored closely during this time. The excreted complex turns the 
urine pink or salmon colored and is sometimes referred to as the “vin 
rose” of iron poisoning. Continue treatment until the urine is clear or 
serum iron levels are within normal limits.
Digoxin immune Fab 
fragmentsDigoxin, Rhinella  sp. (Bufo)  toad toxins, and 
some cardiac glycoside-containing plantsIf serum digoxin level is available: number of vials = serum digoxin level 
(ng/mL) × BW (kg)/100.
If serum digoxin level is not available or if treating a Rhinella (Bufo)  
toad or cardiac glycoside-containing plant toxicosis, start therapy with 
1–2 vials and reassess as needed.

1450  Blackwell’s Five-Minute Veterinary Consult  
Dimercaprol (BAL) Heavy metals, primarily arsenic. Also used 
to chelated lead and mercuryArsenic toxicosis: 5 mg/kg IM × one dose followed by 2.5 mg/kg IM q4h 
for 2 days, q8h for 1 day, and q12h until recovered.
Lead toxicosis: 2.5–5 mg/kg IM as 10% solution q4h on days 1 and 2, 
then q6h on day 3.
Ethanol Ethylene glycol Preferred method: using 7% ethanol (70 mg/mL), load with 8.6 mL/kg 
(600 mg/kg) slow IV × 1 dose and follow with 1.43 mL/kg/hour  
(100 mg/kg/hour) IV CRI for 24–36 hours or until ethylene glycol (EG) 
test is negative.
Flumazenil Benzodiazepine (clonazepam, diazepam, 
lorazepam, others); CNS depression or 
comaDogs and cats: 0.01 mg/kg IV. Short half-life and may need to repeat in 
1–3 hours. Doses 10–20× labeled dose have been used in some 
animals but there is currently no scientific data to support them.
Fomepizole Ethylene glycol Dogs: 20 mg/kg IV over 15–20 minutes as loading dose; 15 mg/kg IV at 
12 and 24 hours; 5 mg/kg IV at 36 hours. Repeat EG test. If positive, 
continue 5 mg/kg IV every 12 hours until negative.
Cats: 125 mg/kg slow IV as a loading dose; 31.25 mg/kg IV at 12, 24, and 
36 hours.
Glucagon Insulin and oral hypoglycemic agent-
induced hypoglycemia; beta and 
calcium channel blockers and tricyclic 
antidepressants bradycardia, AV block, 
and hypotension.50 ng/kg IV bolus in 0.9% sodium chloride followed by 10–15 ng/kg/min 
CRI. May need to increase up to 40 ng/kg/min to maintain euglycemia.
Hydroxycobalamin 
(vitamin B12a; 
B12 precursor)Cyanide 75–150 mg/kg IV
Intravenous lipid 
emulsion (ILE); also 
referred to as 
intravenous fat 
emulsion (IFE)Some lipophilic (fat-soluble) drugs 
including baclofen, barbiturates, 
ivermectin and moxidectin, propranolol, 
tricyclic antidepressants, verapamil, and 
others.Standard protocol:
1.5 mL/kg IV bolus of 20% solution over 5–15 minutes, followed 
immediately with CRI of 0.25 mL/kg/min over 1–2 hours. May repeat 
dose in several hours if signs of toxicity return and serum is not lipemic.
Suggested protocol:
1.5–4 mL/kg IV bolus of 20% over 1 minute, followed by CRI of 0.25 mL/
kg/min over 30–60 min. Individual boluses may be repeated as needed 
up to 7 mL/kg.
Leucovorin Methotrexate; pyrimethamine 
trimethoprim, ormetoprim, othersDogs and cats:
Methotrexate: Varies depending on methotrexate serum concentrations 
(25–200 mg/m2 IV, IM q6h for up to 8 doses).
Pyrimethamine, trimethoprim: 0.1–0.3 mg/kg PO q24h.
Methocarbamol Metaldehyde, permethrin, strychnine, 
tremorgenic mycotoxins, other toxicants 
that cause tremorsDogs: 55–220 mg/kg slow IV. Labeled not to exceed 330 mg/kg/day but 
higher doses may be used in severe poisonings as long as the dog is 
monitored for CNS and respiratory depression.
Cats: 44 mg/kg slow IV, up to 330 mg/kg/day. Labeled not to exceed 330 
mg/kg/day but higher doses may be needed in severe poisonings. 
Monitor for CNS and respiratory depression when using high doses.
Methylene blue Aniline dyes, local anesthetics, 
naphthalene, nitrates and nitrites-
induced methemoglobinemiaCats: Use with extreme caution or not at all.
Dogs: 1–1.5 mg/kg as 1% solution IV over several minutes; may be 
repeated once in 30 min.Antidotes and Useful Drugs: Methods of Treatment ( continued )

Canine and Feline, Seventh Edition  1451
N-acetylcysteine (NAC) Acetaminophen; less often Amanita 
phalloides  mushroom, sago palm, and 
xylitol intoxicationDogs and cats: 140 mg/kg IV or PO × 1 dose, then 70 mg/kg IV or PO q 6 hours 
for 7 doses. The product should be diluted to a 5% solution prior to use. IV 
administration preferred in cats due to low oral bioavailability (20%). 
A variety of other doses have been suggested; most based on extrapolation 
from human literature. Some recommend higher doses (280 mg/kg) and 
others additional doses (up to 17 doses) for massive ingestions. Emesis 
frequently occurs with oral dosing, especially after the initial dose, and an 
antiemetic may be required prior to starting NAC therapy.
Pamidronate Cholecalciferol, calcipotriene, and 
calcitriol-induced hypercalcemia and 
hyperphosphatemiaDogs and cats:
1.3–2 mg/kg diluted in 250–500 mL 0.9% NaCl, IV slowly over several 
hours. Monitor serum calcium levels q12–24h and adjust ancillary 
treatment as needed. If hypercalcemia is still present, a repeated dose of 
pamidronate may be necessary 5–7 days after the initial dose. Very large 
overdoses of cholecalciferol may require a second dose in 3–4 days.
Naloxone Opioid and opiate-induced respiratory and 
CNS depressionDogs and cat: 0.01–0.04 mg/kg, IV, IM, SC; may need to use 0.04 mg/kg 
with larger overdoses. IM and SC route result in slower onset of action 
(5 minutes). Short half-life and may need to repeat in 1–3 hours.
Phytonadione (vitamin 
K1)Anticoagulant rodenticides, warfarin 
tablets2–5 mg/kg PO q24h or divided twice a day.
Pralidoxime (2-PAM) Organophosphates (nicotinic signs) Dose (dogs and cats): 20 mg/kg IM or slow IV (over 30 min) for first dose. 
Repeat dose q8–12h, IM or SC. Rapid IV administration has resulted in 
tachycardia, neuromuscular blockade, laryngospasm, muscle rigidity, 
and death.
Protamine sulfate Heparin Dogs and cats:
1 mg protamine sulfate IV per 100 units heparin to be inactivated.
Give slowly, no faster than 50 mg per over 10 minutes.
Decrease amount of protamine sulfate by 50% for every 30–60 minutes 
that has passed since heparin overdose given.
Pyridostigmine Anticholinergic plants (Cestrum  spp., 
Datura  spp., Solanum  spp, etc.), atropine, 
avermectin and ivermectin, botulism, 
some elapid snake bites, and 
nondepolarizing neuromuscular blocking 
agents (curare, pancuronium, etc.)0.01–0.03 mg/kg/hour CRI. Longer half-life than other similar drugs.
Pyridoxine Isoniazid 71 mg/kg as 5–10% infusion over 30–60 minutes; if total amount of 
isoniazid consumed is known can give on a mg per mg (1:1) ratio.
Succimer (2-3 dimer- 
captosuccinic acid)Lead Dogs and cats: 10 mg/kg PO or rectal q8h × 10 days; retreat only if 
clinical signs are present. Monitor renal values closely in cats.
Trientine (TETA) Copper hepatopathy in dogs Dogs: 10–15 mg/kg PO 1–2 hours before meals. Useful in dogs unable 
tolerate vomiting associated with D-penicillamine.
Yohimbine Xylazine and other alpha-2-adrenergic 
agonists (amitraz, clonidine, xylazine)Dogs and cats: 0.11 mg/kg IV slowly. Shorter half-life than atipamezole.
Abbreviations:  Standard
Comments:
Specific antidotes are not free of side effects and should be used with knowledge and forethought. Many toxicants lack a true antidote, and 
symptomatic and supportive care, including many of the useful drugs found in this table, is imperative for survival of the poisoned patient. Other 
drugs may be needed and the reader is directed to the references below for further information.
 References
Hovda LR. Antidotes and Other Useful Drugs. In: Hovda LR, Brutlag AG, Peterson KL, Poppenga RH, eds., Blackwell’s Five-Minute Clinical 
Companion: Small Animal Toxicology, 2nd ed. Ames, IA: Wiley-Blackwell, 2016.
Khan SA, Common reversal agents antidotes in small animal poisoning. Vet Clin North Am Small Anim Prac 2012, 42:403–406.
Wismer T. Antidotes. In: Poppenga RH, Gwaltney-Brant S, eds., Small Animal Toxicology Essentials. Chichester: Wiley-Blackwell, 2011, pp. 57–70.Antidotes and Useful Drugs: Methods of Treatment ( continued )

1452  Blackwell’s Five-Minute Veterinary Consult  
Table VI-A
Toxic plants and their clinical signs—antidotes and treatment
Plant and Characteristics Clinical Signs Antidotes and/or Treatment
Air plant, cathedral bells ( Kalanchoe  spp.)
Bright red-orange to pink blooms; umbel 
flower pattern.
Plant contains cardiotoxins similar to azalea 
and rhododendrons, concentrated mainly in 
flowersCardiac glycoside causes acute signs 1–3 
hours after ingestion. Signs include 
depression, salivation, diarrhea, 
bradycardia, heart block, tachypnea, 
ataxia, tremors, and paralysisPreventive emesis and/or activated charcoal 
early after ingestion. Treat as a cardiac 
glycoside (see Cardiac Glycoside Plant 
Toxicosis)
Aloe, octopus plant, candelabra plant ( Aloe 
spp.)
Succulent plant, used in folk and herbal 
medicine.
Toxic fraction is anthraquinone glycoside; 
disrupts water and electrolyte balance in 
large intestineAnorexia, depression, vomiting, colic, 
diarrhea, tremors (uncommon), and 
change in urine color. Generally mild in 
natureDrugs for abdominal pain/diarrhea.
Protect airway, treat locally for pharyngitis 
associated with oxalate crystals (rare)
Autumn crocus ( Colchicum autumnale )
Houseplant, garden plant. Typically blooms in 
fall, different from most other bulbs.
Dosages above 6 g/kg BW considered lethal. 
Although the whole plant is toxic, the toxin 
(colchicine) is highest in bulbs.Acute onset 2–12 hours post ingestion. 
Initial signs are nausea, salivation, 
vomiting, colic, diarrhea, incoordination, 
and weakness. Multiple organ systems 
(heart, lungs, and kidneys) also may be 
involved. Potential for coagulopathy 
and elevated serum enzymesInduce emesis if not vomiting. Activated 
charcoal if early. Evaluate CBC and serum 
chemistries, including prothrombin, LDH, CK.
IV fluids, analgesics, anticonvulsants as needed
Baneberry, doll’s eye, cohosh ( Actea  spp.)
Toxic principal is protoanemonin glycoside, as 
well as irritant essential oilsClinical response ranges from dermatitis 
and blistering of skin to oral irritation, 
drooling, pawing at face or mouth, 
emesis, diarrhea, and hematuria.
Neurologic and cardiovascular signs are 
occasionally reportedCleanse mouth thoroughly with water; apply 
appropriate local demulcents; control 
emesis and diarrhea as necessary; monitor 
for organ dysfunction, especially renal 
damage
Belladonna lily ( Amaryllis  spp.)
Potted plant, bulbs are most toxic,
Contains both lycorine alkaloid (systemic 
effects) and insoluble oxalates (local 
pharyngitis)Nausea, vomiting, diarrhea, hypotension, 
depression. Oxalate crystals can cause 
direct pharyngeal irritationGastric lavage, activated charcoal, fluids, and 
supportive treatment
Bittersweet ( Celastrus  spp.)
Weed, vine with red berries.
Immature fruits are toxic.
Toxins are sesquiterpene alkaloids (celapanine, 
celastrine, paniculatine)Gastric irritation, vomiting, diarrhea Fluids, supportive care as needed
Bleeding heart ( Dicentra  spp.)
Garden, woods, potted plant. Roots more toxic 
than leaves.
Toxins are isoquinoline alkaloids 
(apomorphine, cularine, protoberberine)Vomiting, diarrhea, muscle tremors, 
convulsions or paralysisFluids and seizure control
Castor bean ( Ricinus communis )
Garden shrub or ornamental grows to 2 m. Seeds 
are 1 cm, dark and light mottled, and highly 
toxic; chewing the seed greatly increases 
toxicity.
Toxin is ricinSevere, dangerous if seeds chewed before 
Latent period 6–48 hours. Emesis, severe 
and hemorrhagic diarrhea, colic, muscle 
tremors, sudden collapse. Dehydration, 
hypotension, hemolysis and/or 
hemoglobinuriaEmesis for recent exposure: sorbitol if diarrhea 
not present; charcoal, fluids, and 
electrolytes. Monitor electrolytes, liver, 
kidney, adrenal function up to 6 days;
H2 blockers for GI signs; diazepam for seizures;
Antibiotics, lactulose, SAM-e for liver damageToxic Home and Garden Hazards for PetsAppendix VI  Lynn R. Hovda

Canine and Feline, Seventh Edition  1453
Toxic Home and Garden Hazards for Pets ( continued )
Table VI–A
Toxic plants and their clinical signs—antidotes and treatment ( continued  )
Chinaberry tree ( Melia azedarach )
Other common names are Persian lilac, white 
cedar,
Texas umbrella tree.
Ornamental tree in temperate to subtropical 
areas: southern coastal states, Mexican 
border. Berry is most toxic.
Toxins are meliatoxinsSalivation, anorexia, vomiting, diarrhea. 
May be followed by weakness, ataxia, 
excitement or seizures. Fatalities have 
occurred, generally within 2 days post 
ingestionEarly emesis, GI lavage and charcoal are 
considered beneficial. Fluid and electrolyte 
replacement, anticonvulsants, and 
supportive care
Christmas rose ( Helleborus niger )
House and garden plant; entire plant is toxic, 
but fruits are most dangerous. Small 
amounts considered dangerous.
Contains several toxins including ranunculin 
that is converted to protoanemonin when 
chewed, cardenolides, and bufadienolidesHypersalivation, vomiting, anorexia, 
diarrhea followed by cardiac 
arrhythmias, heart block with premature 
beats, premature beats, slow irregular 
pulse.
Potent cardenolide action is greatest riskGastric lavage or emesis; activated charcoal or 
saline cathartics to decontaminate the GI 
tract.
Atropine may be helpful as for other 
cardenolide plants such as Digitalis  spp.
Daphne ( Daphne mezereum )
Landscape shrub; evergreen or deciduous.
Entire plant is toxic. Bitter or acid taste 
discourages consumption, may reduce toxic 
effects. Toxins are tricyclic daphnane and 
diterpenesVesication and edema of the lips and oral 
cavity associated with ingestion. Signs 
progress to salivation, thirst, abdominal 
pain, emesis, hemorrhagic diarrheaAnalgesics to control pain. General GI 
detoxification, medical treatment for 
vomiting and diarrhea. Fluid and electrolyte 
replacement as needed. Monitor body fluids 
and electrolytes
Delphinium/larkspur ( Delphinium  spp.) and 
pheasant’s eye, yellow oxeye ( Adonis  spp.)
Outdoor perennial, gardens, mountains; tall 
with blue, purple, or pinkish flowers. Seeds 
more toxic than leaves.
Toxin is a diterpenoid alkaloidSmall animal poisoning unlikely unless by 
access to seeds.
Early signs are vomiting, colic and 
diarrhea. May progress to trembling, 
ataxia, weakness, lateral recumbencyGI detoxification; demulcents and anti-
diarrheal for GI signs; physostigmine to 
treat muscarinic signs
English holly ( Ilex spp.)
Landscape plant; glossy green leaves with marginal 
spicules. Fruit (drupe) white, yellow, black, red, 
orange. Occurs in forested areas of eastern N. 
America; elsewhere as an ornamental.
Fruit is most likely portion consumed. Fruit and 
leaves contain potentially toxic saponinsNausea, vomiting, diarrhea most common 
from consumption of berries. Some 
animals may be depressed. Clinical 
response most often mild/moderate and 
transientRelief of digestive distress, activated charcoal 
may be helpful. Fluid and electrolyte 
replacement as needed
English ivy ( Hedera helix ), also known as 
Atlantic ivy, Irish ivy, common ivy
Houseplant, or in mild climates used as a 
ground cover. Occurs as a woody, climbing 
or creeping vine. Commonly grown 
throughout North America.
Toxins are triterpenoid saponins.Salivation, thirst, emesis, gastroenteritis, 
diarrhea, dermatitis. Relatively few 
reported cases, most are moderate GI 
irritation. Often moderate or mildSymptomatic relief of GI distress; supportive 
care for vomiting and diarrhea
Golden angel’s trumpet ( Brugmansia  spp.)
Non-native ornamental, similar to jimsonweed. 
Large pendulous flowers, similar to angel’s 
trumpet.
Toxin similar to jimsonweed (tropane alkaloid 
scopolamine) causes anticholinergic effectsTypical anticholinergic effects are 
restlessness, dilated pupils, tachycardia, 
dyspnea, dry mouth, GI atony, rarely 
seizures. Rarely lethalTreat similar to Datura  spp. (see Thorn apple 
below.)
(Continued  )

1454  Blackwell’s Five-Minute Veterinary Consult  
Horse chestnut or Ohio buckeye ( Aesculus  spp.)
Landscape or forest tree; palmate leaves. Native 
range is Midwest, east to Appalachian 
mountains, south into Texas. Planted as 
ornamental/landscape tree as well.
Nuts and twigs most toxic; very early green 
foliage in spring. Horse chestnut highly 
toxic; Ohio buckeye very low toxicity. 
Contain several toxins including saponins, 
anthraquinones, and a coumarin glycosideGastroenteritis, diarrhea, dehydration, 
electrolyte imbalance.
Neurologic signs possible, including 
incoordination, hypermetria, staggering. 
Usually transient, rarely fatal. Recovery 
usual within 24–48 hoursFluid and electrolyte replacement, demulcents, 
and therapy for gastroenteritis. Confine 
animals during neurologic phase
Iris or blue or yellow flag ( Iris spp.)
Perennial garden flower, very commonly 
available. Rootstock (rhizome) most toxic; 
most risk at transplantation. Close to soil 
surface, may be dug up by dogs. Advise 
clients of potential risk.
Rootstock contains purgative toxin known as irisinHypersalivation, vomiting, colic, diarrhea 
which may be hemorrhagic. 
Occasionally irritation of the lips and 
muzzleGI decontamination early.
Fluid and electrolyte therapy as needed
Irish potato ( Solanum tuberosum )
Vegetable garden plant. Vines, green skin, and 
sprouts are toxic.
Toxins vary but are solanine and other 
glycoalkaloidsVomiting, diarrhea, depression, rapid heart 
rate, mydriasis, muscle tremors. Signs 
may vary from atropine like to 
cholinesterase inhibition. Use antidotes 
accordingly and with cautionGI decontamination.
If atropine-like signs predominate: use 
physostigmine. If salivation and diarrhea are 
present: use atropine cautiously
Jerusalem cherry, Winter cherry ( Solanum 
pseudocapsicum )
Common ornamental houseplant.
Toxin is the glycoalkaloid solanine, similar to 
other plants of the nightshade (Solanaceae) 
familySevere GI irritation characterized by 
drooling, vomiting, diarrhea, ulceration, 
depression, and sometimes seizuresGI decontamination if exposure is recent.
If salivation and diarrhea are present and 
severe, use atropine cautiously.
Provide fluid therapy based on condition of 
patient and results of laboratory tests
Lantana ( Lantana camara )
Occurs wild and in gardens in mild temperate 
to tropical areas. Naturalized in southeastern 
coastal states of the USA. Bright orange, 
yellow, red, purple, or pink flowers. Foliage 
and immature berries are most toxic.
Toxins are pentacyclic triterpenoid lantadenes 
A, B, and CWeakness, lethargy, vomiting, diarrhea, 
mydriasis, dyspnea. Continued ingestion 
can lead to chronic disease.
Advanced signs: cholestasis, 
hyperbilirubinemia. Liver changes 
predispose to photosensitizationGI decontamination, activated charcoal for 
acute exposures. Provide fluids and 
respiratory support.
Protect from sunlight and treat for hepatic 
insufficiency
Lily of the valley ( Convallaria majalis )
Ornamental garden plant. Prefers moist, shaded 
areas. Blossoms nodding/drooping on stem.
Toxic principal (cardenolides) persists in dried 
plants; highest concentration in rootsMulti-organ failure. Tremors, thirst, 
vomiting, diarrhea, cardiac arrhythmia/
bradycardia, weakness, shock. Monitor 
for cardiac arrhythmias, shock and 
hyperkalemiaEmesis or gastric lavage. Control dehydration, 
maintain electrolytes; control diarrhea; 
monitor ECG and serum potassium
Lupin, bluebonnet ( Lupinus  spp.)
Common garden ornamental throughout USA; 
wild plants abundant in some regions, 
primarily western USA.
Seeds more toxic than leaves, but plant, seeds, 
and pods are toxic.
Toxin is lupineSigns begin 1–24 hours post exposure. 
Salivation, ataxia, mydriasis, depression 
or seizures, disorientation, dyspnea.
Liver and kidney damage may develop 
from continued ingestion.
Lupines are teratogenic in ruminants. Risk 
in small animals is not well knownGI decontamination with activated charcoal 
for acute exposure.
Anticonvulsants may be needed if neurologic 
signs are severeToxic Home and Garden Hazards for Pets ( continued )
Table VI–A

Canine and Feline, Seventh Edition  1455
Mexican breadfruit, Swiss cheese plant, 
hurricane plant ( Monstera deliciosa )
Stems and leaves contain insoluble calcium 
oxalate spicules (raphides)Chewing on the plant releases oxalate 
spicules into mouth, tongue and lips.
Response is immediate irritation, pain, 
salivation, and inflammation. Signs 
include pawing at face, drooling, and 
vomiting; potential interference with 
upper airwayCleanse mouth thoroughly with water.
Apply local and/or systemic anti-inflammatory 
agents based on clinical condition of patient
Mistletoe ( Phoradendron  spp.)
Access to pets in homes at holiday time. Oval 
evergreen leaves with white berries.
Leaves, stems, and berries are moderately 
toxic, contain toxic amines and proteinsVomiting, GI pain, diarrhea; ataxia, 
hypotension, occasional seizures, 
cardiovascular failure.
Principal risk may be from use during 
holiday seasonFluid and electrolyte replacement; demulcents 
for gastroenteritis
Monkshood ( Aconitum  spp.)
Perennial garden ornamental.
Entire plant is toxic, contains diterpene 
alkaloids that are primarily neurotoxicInterferes with inactivation of Na+ 
channels in nerves.
Salivation, vomiting, diarrhea. Muscle 
tremors, weakness, cardiac arrhythmia 
and/or heart failure; respiratory 
depressionGI decontamination, fluid and electrolyte 
replacement. Manage similar to digitalis 
glycoside overdose, with caution for 
potassium administration
Morning glory ( Ipomoea purpurea  and 
Ipomoea tricolor )
Garden annual, potted plant.
Seeds most toxic. Increased risk when seeds 
are pre-soaked, consumed by dogs. Indole 
alkaloid toxin similar to ergot alkaloids; 
abused as hallucinogenNausea, mydriasis, ataxia, muscle tremors, 
hallucinations, decreased reflexes, 
diarrhea, hypotensionDark, quiet surroundings; tranquilization as 
needed.
GI decontamination is not routinely 
recommended
Mountain laurel ( Kalmia  spp.)
Native of eastern and southeastern woods, 
mountains. Both leaves and flowers are 
toxic. Honey from nectar also toxic.
Toxins are diterpenoids, in particular 
grayanotoxins I and IIOral irritation, salivation, projectile 
vomiting, diarrhea, weakness, impaired 
vision, bradycardia, hypotension, AV 
blockActivated charcoal, fluid replacement, and 
respiratory support as needed
Narcissus, daffodil, jonquil ( Narcissus  spp.)
Garden ornamental bulb. Bulb is most toxic.
Contains lycorine alkaloidNausea, vomiting, salivation, hypotension, 
diarrhea.
Prolonged signs may cause dehydrationGastric lavage, activated charcoal, fluid 
replacement, supportive treatment for 
gastroenteritis
Nettle ( Urtica  spp.)
Garden or waste area weed.
Hairs on leaves contain toxin that enters skin on 
contact. Most common in hunting or outdoor 
free-roaming dogs. Toxins are biogenic 
amines (acetylcholine, histamine, etc.)Oral irritation and pain, hypersalivation, 
swelling and edema of nose and 
periocular areas or other areas of skin 
contactAntihistamines and analgesics. Local or 
systemic anti-inflammatory supportive 
therapy to treat affected contact areas
Persian violet, sowbread ( Cyclamen 
persicum )
Popular florists’ plant; widely available.
Irritant saponins in all parts of the plant, 
especially tubers or rootsChewing plant parts causes oral irritation 
with drooling, vomiting and diarrhea. 
Occasional hemoglobinuria may color 
urine red-brown.
Large amounts may cause cardiac 
arrhythmias, seizures and rarely 
mortalityControl vomiting and diarrhea if severe; 
administer fluids as needed.
Monitor urine for color and/or hemoglobin.
Control seizures and cardiac arrhythmias as 
neededToxic Home and Garden Hazards for Pets ( continued )
Table VI–A

1456  Blackwell’s Five-Minute Veterinary Consult  
Philodendron  spp.
Very common indoor ornamental vine.
Toxic principal is insoluble oxalateChewing on the plant releases oxalate 
spicules into mouth, tongue and lips. 
salivation, and inflammation.
Signs include pawing at face, drooling, and 
vomiting; also potential interference 
with upper airwayCleanse mouth thoroughly with water.
Poinsettia ( Euphorbia pulcherrima )
Garden or potted plant, especially during 
Holiday season.
Sap of stem and leaves mild irritant. Contains 
a variety of diterpenoid euphorbol estersIrritation of mouth: may cause vomiting, 
diarrhea, and dermatitis.
Usually transient and not life-threateningDemulcents for local lesions; fluids to prevent 
dehydration
Rosary pea, precatory bean ( Abrus precatorius )
Native of Caribbean islands.
Seeds (when broken or chewed) are highly 
toxic. Seeds used in ornamental jewelry in 
some countries. Illegal to import into USA.
Toxin is abrinSigns may be delayed up to 2 days after 
ingestion. Early signs are nausea, 
vomiting, diarrhea (often hemorrhagic) 
followed by weakness, tachycardia, 
possible renal failure, coma, deathEmesis or lavage followed by activated 
charcoal, demulcents, fluids, and 
Early and thorough detoxication is important 
for survival
Thorn apple, jimsonweed ( Datura stramonium )
Annual weed, some species are ornamental 
(Datura metel ).
Entire plant is toxic, but seeds are most toxic 
and available.
Toxins are tropane alkaloids (hyoscyamine and 
scopolamine) with effects similar to atropineThirst, disturbances of vision, delirium, 
mydriasis, tachycardia, hyperthermia, GI 
atony/constipation.
Commonly described as “Hot as a pistol, 
blind as a bat, red as a beet, mad as a 
hatter”GI decontamination if early after ingestion.
Parasympathomimetic drug (e.g., 
physostigmine)
Tulip ( Tulipa  spp.) and Hyacinth ( Hyacinthus  spp.)
Poisoning usually occurs when dogs consume 
available bulbs or dig up freshly planted 
bulbs.
Toxic principal includes allergenic lactones and 
similar alkaloidsSigns reflect direct irritation and include 
drooling, nausea, vomiting, diarrhea, 
dyspnea, tachycardia, and hyperpneaGI decontamination if early after ingestion.
agents based on clinical condition of 
patient. Monitor and control 
gastrointestinal effects; medicate as needed 
for tachycardia and dyspnea
Tobacco ( Nicotiana tabacum )
Garden plant, weed, cigarettes.
Entire plant toxic. Nicotine alkaloid is toxic principalRapid onset of salivation, nausea, emesis, 
tremors, incoordination, ataxia, collapse 
and respiratory failureAssist ventilation, provide vascular support. 
Gastric lavage with activated charcoal
Wisteria ( Wisteria  spp.)
Woody vine or shrub with bluish purple to 
white legume flowers. Entire plant is toxic.
Toxin is a glycoprotein lectinNausea, abdominal pain, prolonged 
vomiting; diarrhea.
Signs may persist 2–3 daysAntiemetics and fluid replacement therapy
Yellow jessamine ( Gelsemium sempervirens )
Mild temperate to subtropical climates; mainly 
SE United States. Yellow trumpet-shaped 
flowers grow on evergreen vines.
Neurotoxic alkaloids and sempervirine, an 
indole, are toxinsWeakness, ataxia, clonic/tonic seizures, 
paralysis, respiratory failureGI decontamination early in course of 
toxicosis. Symptomatic and supportive 
therapy for respiration.
Fluid replacement therapy as needed
Suggested Reading:
Barr AC. Household and garden plants. In: Peterson ME, Talcott PA, eds., Small Animal Toxicology, 3rd ed. St Louis, MO: Elsevier/Saunders, 2013, pp. 357–400.
Burrows GE, Tyrl RJ. Toxic Plants of North America. Ames, IA: Iowa State University Press, 2001.
Frohne D, Pfander HJ. Poisonous Plants, 2nd ed. Portland, OR: Timber Press, 2005.
Williams MC, Olsen JD. 1984. Horse chestnut: a multidisciplinary clinical review. Am J Vet Res 1984, 45(3):539–542.Toxic Home and Garden Hazards for Pets ( continued )
Table VI–A

1457Toxic Home and Garden Hazards for Pets (continued )
Table VI-B
Herbal toxicities
Class Toxic Principle Genus Species Common Names Clinical Signs Treatment Overview Popular Usage
Allergenic ArabinogalactanEchinacea purpurea Purple coneflower Vomiting, diarrhea Symptomatic/supportive care. Cold/flu support
Immune stimulant
Alpha-2 adrenergic 
blocking agentYohimbine
Corynanthine 
(rauhimbine)
Raubasine
(δ-yohimbine)Pausinystalia johimbe Yohimbine Hyperactivity, agitation, tremors, 
seizures, vomiting, diarrhea, 
abdominal pain, tachycardia, 
hypertension followed by 
profound hypotension, 
hypoglycemiaDecontamination; monitor CNS 
and CV signs; control agitation, 
tremors, seizures; monitor blood 
glucose; IV fluids; dextrose PRNHypertension
Angina
“Herbal Viagra”
Anticoagulant Hydroxycoumarin, 
bisabololMatricaria recutita , 
Chamaemelum nobileChamomile Vomiting, diarrhea, lethargy, 
rarely epistaxis, hematoma 
(cats)Monitor coagulation, symptomatic 
and supportive care, very rarely 
blood transfusionSedative
Gastrointestinal ulcers
Cationic detergents Quaternary 
ammonium 
compoundsCitrus  × paradisi Grapefruit seed extract 
(GSE)Drooling, vomiting ± blood, 
weakness, anorexia, 
hyperthermia, oral/esophageal 
irritation or ulceration, dermal 
erythema, pain, ulcerationDilution, carafate slurries, H2 
blocker or PPI, fluids, nutritional 
support, broad-spectrum 
antibiotic, pain controlDisinfectant
Antifungal
Essential oils Melaleuca oil, 
pulegone, 
menthofuranMelaleuca alternifolia ,
Mentha pulegiumTea tree oil, Pennyroyal 
oilOrally: vomiting, diarrhea, CNS 
depression, hepatotoxicity, 
aspiration pneumonia. 
Dermally:transient paresisDermal: bathe in liquid dish soap. 
Oral: fluids, N-acetylcysteine, 
monitor liver enzymes. Pain 
control, thermoregulation PRNGermicidal
Fungal infections
Antiseptic
Flea control
Liquid potpourri Clinical signs are dependent on 
the type of essential oil and 
route of exposure. May 
include GI signs, corrosive oral 
lesions, drooling, vomiting, 
ataxia, coma, respiratory 
distress, hypothermia or 
hyperthermia, hypotension, 
acute liver failureDermal: bathe in mild liquid dish 
soap. Oral: Do not induce emesis 
or give activated charcoal. 
Irrigate the oral cavity. Fluids, 
anti-emetic, GI protectants, 
nutritional support, thoracic 
radiographs if indicated, 
monitor liver and kidney values 
in large exposures, broad-
spectrum antibiotics and 
hepatoprotectants if indicatedInsecticides
Aromatherapies
Room/air fresheners
Personal care
products
Massage oils
Antibacterials
Flavorings
Herbal remedies
Cleaners—citrus oilsMethyl salicylate Oil of wintergreen
Oil of sweet birch
d-Limonene Citrus oil
Terpenic oils Pine oils
Benzyl alcohol, 
benzyl acetate, 
benzyl benzoateYlang ylang oil
Menthol Peppermint oil
Alcohols and 
aldehydesCinnamon oil
GABA Inhibitor 4-Methoxypyridoxine 
(MPN)Ginkgo biloba Gingko, maidenhair tree
Dietary supplements 
pose less risk than 
fruit/seeds due to 
lower concentrationAnorexia, vomiting, diarrhea, 
agitation, clonic tonic seizuresDecontamination (emesis, 
activated charcoal), GI 
protectants, anticonvulsants
Antidote: Pyridoxal phosphate/
pyridoxine (active form of 
vitamin B6)Antitussive
Expectorant
Cognitive function 
(although no 
scientific proof)
(Continued  )Appendix VI  Colleen M. Almgren

Hypoglycemics Alpha lipoic acid 
(ALA)Thioctic acid Hypersalivation, vomiting, 
hypoglycemia, increased 
hepatic and/or renal enzymes, 
death (ALA)Decontaminate, IV fluids, monitor 
blood glucose, manage 
hypoglycemia, monitor liver 
enzymes, hepatoprotectants 
(NAC-Mucomyst, Denamarin)Diabetic treatment
Sugar substituteAmanita  Mushroom 
poisoning (ALA)CinnamonCinnamomum cassia Cinnamon
Xylitol Xylitol
MAO inhibitor HypericinHypericum perforatum St. John’s wort Depression, vomiting, diarrhea, 
rarely tremors, seizuresDecontamination, symptomatic and 
supportive care, cyproheptadine 
for serotonin syndromeAntidepressant
Insomnia
Methylxanthines Caffeine, 
theobromineCamellia sinensis , 
Paullinia cupana , 
Cola acuninata , 
Theobroma cacaoEpigallocatechin gallate 
or ECGC (green tea), 
guarana, cocoa, cola, 
kola nut, chocolateAgitation, hyperactivity, polyuria, 
polydipsia, cardiac 
arrhythmias, tremors, seizuresDecontamination, fluid diuresis, 
monitor CV and CNS, manage 
arrhythmias, tremors, seizures, 
symptomatic and supportive careWeight loss,
Herbal “NoDoz”
Polysulfated 
glycosamino-
glycan (PSGAG)PSGAG manganese Glucosamine
Chondroitin sulfateAdequan®, Cosequin®, 
Dasuquin® Many 
other brandsOral: vomiting, diarrhea, 
polydipsia, hepatopathy. IM: 
transient dose-dependent 
prolongation of PT, aPTT, 
reduced platelet aggregation, 
diathesisManage vomiting and diarrhea, 
baseline liver enzymes if large 
ingestion. Coagulopathies only 
expected with injectable 
overdoses or if significant liver 
enzyme elevations occur, 
monitor clotting parametersArthritis
Chondroprotective
Salicylates Methyl salicylateGaultheria procumbensWintergreen extract GI upset, GI ulcers, hyperthermia, 
hepatoxicity, coagulopathies, 
comaDecontamination, GI protectants, 
fluids, monitor for acidosis, 
monitor liver and kidney values, 
liver protectants, monitor 
clotting parametersAnti-inflammatory
Analgesic
Salicin
Salicylic acid Willow bark
Sedative ValpotriatesValeriana officianalis Valerian Lethargy, sedation Generally home care, prevent injury Sedative
Sleep aid
Serotonin 
syndrome5-Hydroxytryptophan 
(5-HTP)
Caution : chewables 
may also contain 
xylitolGriffonia simplicifolia 5-HTP
OxitriptanVomiting, diarrhea, tremors, 
seizures, ataxia, hyperesthesia, 
tachycardia, hyperthermia, 
mydriasis, transient blindness, 
depressionDecontamination, IV fluids, 
acepromazine or chlorpromazine 
for agitation, methocarbamol for 
tremors; phenobarbital or propofol 
for seizures. Avoid 
benzodiazepines. Cyproheptadine 
for serotonin syndrome. Monitor 
for DIC if significantly hyperthermicAntidepressant
Appetite suppressant
Sleep aid
Sympathomimetics Ephedrine
Pseudoephedrine
SynephrineEphedra sinica Ma huang Hyperthermia, hypertension, 
tachycardia, tremors, seizures, 
hallucinations, agitation, 
serotonin syndromeDecontamination, monitor CV/CNS 
signs. Acepromazine for agitation. 
Cyproheptadine for serotonin 
syndrome. Beta blockers for 
tachycardia. Avoid benzodiazepinesWeight loss
Body building
Herbal “ecstasy”
DecongestantsToxic Home and Garden Hazards for Pets (continued )
Table VI-B
Herbal toxicities (continued  )
1458

Sida cordifolia Indian common mallow
Citrus aurantium Bitter orange
Essential Oils:
Bischoff K, Guale F . Australian tea tree (Melaleuca alternifolia) oil poisoning in three purebred cats. J Vet Diag Invest 1998, 10:208–210.
Cohen SL, Brutlag AG. Tea tree oil/melaleuca oil. In: Hovda LR, Brutlag AG, Poppenga RH, Peterson KL, eds., Blackwell’s Five-Minute Veterinary Consult Clinical Companion: Small Animal Toxicology, 2nd ed. 
Ames, IA: Wiley-Blackwell, 2016.
Foss TS. Liquid potpourri and cats. Vet Tech 2002, 686–698.
Kore AM, Kiesche-Nesselrodt A. Toxicology of household cleaning products and disinfectants. Vet Clin North Am Small Anim Pract 1990, 20(2):525–537.
Lee JA, Budgin JB, Mauldin EA. Acute necrotizing dermatitis with septicemia following application of a d-limonene-based insecticidal shampoo in cat. J Am Vet Med Assoc 2002, 221(2):258–262.
Poppenga RH. Essential oils/liquid potpourri. In: Hovda LR, Brutlag AG, Poppenga RH, Peterson KL, eds., Blackwell’s Five-Minute Veterinary Consult Clinical Companion: Small Animal Toxicology, 2nd ed. Ames, 
IA: Wiley-Blackwell, 2016, pp. 585–591.
Richardson JA. Potpourri hazards in cats. Vet Med 1999, 94(12):1010–1012.
Rousseaux CG, Smith RA, Nicholson S. Acute Pine-Sol toxicity in a domestic cat. Vet Human Toxicol 1986, 28:316–317.
Schildt JC, Beal MW, Jutkowitz LA. Potpourri oil toxicity in cats: 6 cases (2000–2007). J Vet Emerg Crit Care 2008, 18(5):511–516.
Tauer D. Phenols and pine oil. In: Hovda LR, Brutlag AG, Poppenga RH, Peterson KL, eds., Blackwell’s Five-Minute Veterinary Consult Clinical Companion: Small Animal Toxicology, 2nd ed. Ames, IA:  
Wiley-Blackwell, 2016, pp. 646-454.
Villar D, Knight MJ, Hansen SR, and Buck WB. Toxicity of melaleuca oil and related essential oils applied topically on dogs and cats. Vet Hum Tox 1994, 36:139–142.
Alpha lipoic acid (ALA):
Hill AS, Werner JA, Rogers QR, et al. Lipoic acid is 10 times more toxic in cats than reported in humans, dogs, or rats. J Anim Physiol Anim Nutr 2004, 88(3–4):150–156.
Loftin EG, Lee VH. Therapy and outcome of suspected alpha lipoic acid toxicity in two dogs. J Vet Emerg Crit Care 2009,19(5):501–506.
Zicker SC, Avila A, Joshi DK, et al. Pharmacokinetics of orally administered DL-alpha-lipoic acid in dogs. Am J Vet Res 2010, 71(11):1377–1383.
Zicker SC, Hagen TM Joisher N, et al. Safety of long-term feeding of dl-alpha-lipoic acid and its effect on reduced glutathione:oxidized glutathione ratios in beagles. Vet Ther 2002, 3(2):167–176.
5-Hydroxytryptophan (5-HTP):
Gwaltney-Brant SM, Albertsen JC, Khan SA. 5-Hydroxytryptophan toxicosis in dogs: 21 cases (1989-1999). J Am Vet Med Assoc 2000, 216:1937–1940.
Polysulfated glycosaminoglycan joint supplements (glucosamine, chondroitin):
Borchers A, Epstein SE, Gindiciosi B, et al. Acute enteral manganese intoxication with hepatic failure due to ingestion of a joint supplement overdose. J Vet Diag Invest 2014, 26(5):658–663.
Breese McCoy SJ, Bryson JC. High dose glucosamine associated with polyuria and polydipsia in a dog. J Am Vet Med Assoc 2003, 222:431–432.
Brim TA, Center V, Wynn SG, et al. More on accidental overdose of joint supplements. J Am Vet Med Assoc 2010, 236(5):509–510.
Khan SA., McLean MK, Gwaltney-Brant S. Accidental overdosage of joint supplements in dogs. J Am Vet Med Assoc 2010, 236(10):1061–1062.
Khan KN, Andress JM, Smith PF . Toxicity of subacute IV manganese chloride administration in beagle dogs. Toxicol Pathol 1997, 25:344–350.
Nobles IJ, Khan S. Multiorgan dysfunction syndrome secondary to joint supplement overdosage in a dog. Can Vet J 2015, 56:361–364.
Sympathomimetics:
Means C. Ma huang: all natural but not always innocuous. Vet Med 1999, 94:511–512.
Means C. Ephedra/ma huang. In: Osweiler, Hovda, Brutlag, Lee, eds. Five-Minute Veterinary Consult Clinical Companion. Ames, IA: Wiley-Blackwell, 2011, pp. 521–526.
Ooms TG, Khan SA, Means C. Suspected caffeine and ephedrine toxicosis resulting from ingestion of an herbal supplement containing guarana and ma huang in dogs: 47 cases (1997–1999). J Am Vet Med Assoc 
2001, 218:225–229.
Herbals (general):
Poppenga RH, Gwaltney-Brant S, eds. Dietary supplements and herbs. In: Small Animal Toxicology Essentials. Chichester, UK: Wiley Blackwell, 2013, pp. 161–169.
Wynn SG, Fougere BJ. Veterinary Herbal Medicine. St. Louis, MO: Mosby, 2007, pp. 513–514.Toxic Home and Garden Hazards for Pets (continued )
Table VI-B
1459

1460  Blackwell’s Five-Minute Veterinary Consult  
Table VI-C
Household cleaners, disinfectants, and solvents—products, clinical signs, and treatment
Products Toxicity and Clinical Signs Treatment
SOAPS, DETERGENTS, AND  
CLEANING AGENTS
Soaps (fatty acid salts)—includes 
commercial bar soaps, some 
liquid hand soaps, laundry bar 
soaps, homemade soaps, some 
baby and infant productsLow order toxicity Generally dilution with water and observation is all that 
is required. Can typically be managed by pet owner. 
Fluids and electrolytes should be used to replace fluid 
loss from excessive vomiting and diarrhea. If vomiting 
has not yet occurred, emesis should be induced in 
noncorrosive bar soap ingestions >20 g soap/kg BW. 
Eyes should be irrigated with tepid water or isotonic 
saline for 10–15 minutes and observed for signs of 
irritation. Any exposed skin and hair coat should be 
rinsed with tepid water for 15 minutes.
Anionic detergents (sulfonated or 
phosphorylated straight-chain 
hydrocarbons)—includes most 
laundry detergents, some 
automatic dishwashing 
detergents, and some shampoos. 
Common detergents include 
alkyl sodium sulfate, alkyl 
sodium sulfonate, dioctyl sodium 
sulfosuccinate, linear alkyl 
benzene sulfonate, sodium lauryl 
sulfate, others. Hard water 
“boosters” or “builders” such as 
sodium carbonate, sodium 
phosphate, and sodium silicate 
are often addedGenerally slight to moderate toxicity with high alkaline 
(pH >12) and potentially corrosive automatic 
dishwashing detergents, including pods or complete 
packs, the exception. Irritation to the GI tract with 
discomfort, vomiting, and diarrhea the most common 
signs. Absorption occurs through the GI tract and 
irritated skin; IV hemolysis has been reported. 
Repeated dermal exposure may result in irritation. 
Ocular exposure may cause conjunctivitis and 
irritation; ocular exposure to automatic dishwashing 
detergents may result in corneal erosion and opacity.
Laundry pods or complete packs have caused more 
serious problems than expected based on the 
ingredients. The reason is unknown but may be 
related to increased amounts ingested due to a 
concentrated product packageDepends on specific product and amount ingested. 
With most products, dilution with water and 
replacement of fluid and electrolyte losses 
secondary to vomiting and diarrhea are all that are 
required. GI protection as needed. Serum should 
be monitored for hemolysis. Skin and hair coat 
should be rinsed well with tepid water for 15 
minutes to prevent exposure, especially those 
animals that are known to self-groom. Eyes should 
be irrigated well for 10–15 minutes with tepid 
water or isotonic saline and monitored closely for 
irritation. Animals exposed in any manner to 
automatic dishwashing detergents or laundry pods 
should be examined and monitored for corrosive 
type injuries and aspiration pneumonia
Cationic detergents (quaternary 
ammonium compounds with 
aryl or alkyl substituent groups, 
often a very long hydrophobic 
carbon chain with a halogen 
such as chloride or iodide is 
attached)—includes fabric 
softeners, sanitizers, germicides. 
Compounds such as 
benzethonium chloride, 
benzalkonium chloride, and cetyl 
pyridinium chloride are used as 
cationic detergents. Liquid 
potpourris, covered elsewhere, 
are also in this groupHighly toxic compounds. Effects are concentration 
dependent with 1% concentrations causing 
irritation and damage to mucous membranes and 
7.5% concentrations resulting in corrosive burns 
to the mouth, tongue, pharynx, and esophagus. 
Cats can develop lesions at 2% concentration.
GI signs at high concentration include profuse 
salivation, and vomiting ± blood. Other signs 
include shock at any stage of exposure, muscle 
weakness, fever, CNS and respiratory depression, 
seizures, collapse and coma
Dermal effects are concentration dependent. Hair 
loss and skin ulceration are frequently seen in cats 
and inflammatory lesions on the paws in dogs.
Ocular signs after exposure are concentration 
dependent and range from irritation and 
discomfort to corneal damage and ulcerationDepends on the concentration of the product and route 
of exposure. Animals ingesting product should be 
given frequent drinks of water if stable. Vomiting 
should not be induced, especially when the 
concentration is greater than 7.5%. Activated 
charcoal is not typically indicated. The mouth and 
oropharynx should be examined for lesions and those 
animals with continued profuse salivation, stridor, or 
dysphagia should undergo endoscopic examination 
for analysis of mucosal damage. Supportive care 
includes IV fluids as needed, attention to respiratory 
effort, adequate caloric intake, seizure medication as 
needed, and close monitoring for shock.
GI protection indicated with all exposures. Ancillary 
therapies may include pain control and repeated 
wound lavage. Exposed skin and hair coat should be 
washed with tepid water and mild soap for at least 
15 minutes and monitored for irritation and 
ulceration. The eyes should be thoroughly evaluated 
and irrigated with isotonic saline for 20 minutes 
followed by a slit lamp examination. Further 
treatment depends on the examination resultsAppendix VI  Tabatha Regehr

Canine and Feline, Seventh Edition  1461
Nonionic detergents (uncharged 
aqueous solutions)—includes 
hand dishwashing detergents, 
shampoos, few laundry 
detergents. Alkyl ethoxylate, 
alkylphenoxy polyethoxy ethanol 
(alcohol ethoxylates), and 
polyethylene glycol stearate are 
examplesPrimarily of low toxicity after ingestion. Ocular 
exposure may result in irritationDilution with water and observation normally all that is 
required. Can typically be managed by pet owner. IV 
fluids and electrolytes may be used to replace fluid 
losses from excessive vomiting and diarrhea. GI 
protection may be needed. Eyes should be irrigated 
with tepid water or isotonic saline for 10–15 minutes 
and observed for signs of continued irritation. Any 
exposed skin and hair coat should be rinsed well with 
tepid water to prevent reexposure
CORROSIVES
Acids (pH <7; strong acids pH 
<2.5–3)—includes rust 
removers, drain and toilet bowl 
cleaners, car battery acid, gun 
barrel cleaning fluids, other 
metal cleaners, hair wave 
neutralizers, some swimming 
pool cleaning agents. 
Hydrochloric acid (muriatic acid), 
sulfuric acid, nitric acid, oxalic 
acid, phosphoric acid, and 
sodium bisulfite (sodium acid 
sulfate) are all acid corrosives. 
Hydrofluoric acid, a rust remover 
product, carries a special 
warningSigns are concentration and time dependent 
although in general these are highly toxic 
substances when below a pH of 2.0. Acids 
typically have a localized necrotic effect and 
rarely cause full-thickness mucous membrane 
lesions. Exposure in animals results in immediate, 
intense pain which typically limits further 
exposure.
Corrosive mucous membranes burns are initially 
gray to milky white, turning black as an eschar 
forms. Stricture formation may follow in several 
weeks. The animal may vocalize or become 
lethargic; excessive panting may indicate pain 
and inability to swallow may be noted. Other 
effects are hematemesis, abdominal pain, 
polydipsia, epiglottal edema with secondary 
respiratory distress, and shock. Secondary 
pneumonitis results from aspiration or exposure 
to acid vapors.
Serious burns result from ocular or dermal 
exposure. Pain is severe. Acids tend to penetrate 
the eye more slowly than bases and may result 
in a delayed corneal damage including corneal 
and conjunctiva necrosis.
Hydrofluoric acid (HF) penetrates tissues and 
poisoning can occur through ingestion, 
inhalation, or skin or eye exposure. Signs are 
often delayed and pain may not be immediately 
evident. Once systemic, HF binds with calcium 
ions producing insoluble calcium fluoride. Severe 
pain and swelling as well as hypocalcemia result. 
In severe exposures death from cardiac arrest 
may occurAll exposures should be diluted immediately with water. 
Attempts to neutralize the burn with other chemicals 
are contraindicated as is emesis or gastric lavage. 
Activated charcoal is ineffective in binding acid 
corrosives and should not be administered. GI 
protection indicated with all exposures. Ancillary 
wound lavage. and pain control as needed. 
Supportive care including IV fluids may be indicated. 
Therapy for shock may be required as uncorrected 
circulatory collapse can lead to renal failure, ischemic 
lesions in vital organs, and acute death. The presence 
of severe pharyngeal edema indicates the need for an 
endotracheal or tracheostomy tube. Esophageal 
complications are less common with acid exposures 
than alkali ingestions. If necessary, endoscopy should 
be carefully performed 12–24 hours after exposure to 
determine the extent of injury. The procedure should 
be stopped at the first sign of mucosal damage. 
Radiographic examination is another alternative.
Affected skin and hair coat should be irrigated for at 
least 15 minutes with copious amounts of tepid 
water and monitored for lesions.
Affected eyes should be irrigated for 20–30 minutes 
with isotonic saline followed by an examination 
with a slit lamp. Further treatment depends on the 
result of the examination.
Any deterioration in the animal’s signs necessitates a 
second examination.
Hydrofluoric acid exposures require immediate attention 
even though they may not show any signs. Caretakers 
should take precautions to protect themselves when 
bathing or applying medications. Exposed areas 
should be washed well with cool water and ice packs/
cold compresses applied to slow diffusion of the 
fluoride ion. Calcium gluconate gel applied liberally to 
the affected area will help bind fluoride. If calcium 
gluconate gel is not readily available, the area can be 
soaked in any magnesium hydroxide containing 
antacid product until the gel is locatedToxic Home and Garden Hazards for Pets ( continued )
Table VI–C
Household cleaners, disinfectants, and solvents—products, clinical signs, and treatment ( continued  )

1462  Blackwell’s Five-Minute Veterinary Consult  
Bases (pH >7; strong base pH 
>11.5–12; some references state 
>10)—includes drain and oven 
cleaners, cleaning agents, toilet 
bowl cleaners, washing products. 
Lye (sodium or potassium 
hydroxide or caustic soda), 
sodium carbonate (washing 
soda or soda ash), sodium 
metasilicate, and ammonium 
hydroxide are alkaline 
ingredients present in many of 
these productsRapid liquefaction necrosis on contact with deep, 
penetrating ulcers. Ingestion may result in full 
thickness esophageal burns with secondary 
stricture formation. Little pain on contact so 
animals are not repelled allowing for a more 
significant exposure to occur.
The remaining signs are similar to those found 
under corrosive acidsAll exposures should be diluted immediately with 
water. Attempts to neutralize with other chemicals 
Activated charcoal is ineffective in binding and 
should not be administered. Supportive care includes 
IV fluids and adequate nutrition. GI protection 
indicated with all exposures. Corticosteroids have 
been recommended to decrease stricture formation, 
but their use is controversial. Antibiotics should be 
used in animals with known perforations or 
infections. Therapy for shock may be required as 
uncorrected circulatory collapse can lead to renal 
failure, ischemic lesions in vital organs, and acute 
death. The presence of severe pharyngeal edema 
indicates the need for an endotracheal or 
tracheostomy tube. Endoscopy should be carefully 
performed 12–24 hours after exposure to determine 
the extent of injury. The procedure should be stopped 
at the first sign of mucosal damage. Radiographic 
examination is another alternative.
Affected skin and hair coat should be flushed for at 
results of the examination.
second examination
DISINFECTANTS
Bleaches —includes common 
household bleach (3–6% sodium 
hypochlorite); industrial or 
swimming pool bleach (up to 
50% sodium hypochlorite); 
powdered bleach (calcium 
hypochlorite, sodium 
dichloroisocyanurate), non-
chlorine or colorfast bleach 
(sodium carbonate peroxide, 
hydrogen peroxide, sodium 
perborate)The toxicity of chlorine bleach depends on the pH and 
concentration of the hypochlorite ion. Exposed 
animals may smell like chlorine and their exposed 
hair coat bleached. Household chlorine bleach 
products are mild to moderate irritants and generally 
not associated with significant tissue destruction. 
Common clinical signs secondary to ingestion include 
oral irritation, salivation, abdominal pain, and 
vomiting. Inhalation of fumes may result in coughing, 
gagging and retching. Systemic reactions are rare. 
Oral, pharyngeal, esophageal, and gastric burns have 
been reported from household chlorine bleach 
ingestions but are rare.
The more concentrated hypochlorite solutions and 
bleach powders can produce corrosive effects.
Non-chlorine bleach products are of low order toxicity 
with gastric irritation and vomiting the most 
commonly reported signs. Borate containing products 
decompose to peroxide and borate resulting in a 
more alkaline and potentially irritating productAll oral exposures should be diluted with water. 
Exposed skin and hair coat should be washed with 
a mild soap and copious amounts of water; eyes 
should be irrigated with isotonic saline for 15 
minutes. Animals inhaling chlorine bleach fumes 
should be moved to fresh air. The incidence of 
esophageal damage is low so endoscopy is not 
routinely recommended. Animals with dysphagia, 
dyspnea, or severe oropharnyngeal burns should 
undergo careful endoscopic examination and 
treated as needed for corrosive injuries. Ancillary 
therapies may include gi protection, pain control, 
and repeated wound lavage.
water and monitored for lesionsToxic Home and Garden Hazards for Pets ( continued )
Table VI–C

Canine and Feline, Seventh Edition  1463
Phenols (coal tar-derived aromatic 
alcohols)—chlorophenols, 
phenylphenols in a variety of 
concentrations and products; 
some concentrated commercial 
products contain up to 50% 
pure phenol. Found in household 
cleaning products, medicated 
shampoos, disinfectants, and 
scentsConsidered highly toxic and a medical emergency 
due to rapid absorption by inhalation, ingestion, 
or dermal exposure. Cats are more sensitive than 
dogs. The LD50 of pure phenol in dogs is 0.5 g/kg 
BW (orally) and cats 80 mg/kg BW (unknown 
route). Concentrations 1–5% may cause tissue 
irritation and dermal burns, 5–10% dermal, oral 
and gi burns are possible, and at >10% corrosive 
damage to all tissues are expected.
Oral exposure causes burns to the mouth, 
oropharynx, and esophagus. Hypersalivation, 
panting, agitation, and vomiting progress to 
tremors, cardiac arrhythmias, shock, and coma. 
Methemoglobinemia, respiratory alkalosis, and 
renal and hepatic damage may develop.
Dermal and ocular exposure results in a short 
period of intense pain followed by local 
anesthesia. Necrotic skin areas are white 
followed in a few days by a dry, gray black 
eschar. Ocular exposure results in severe corneal 
burns and erosionsOral dilution is recommended as soon as possible but 
choice diluent is considered controversial. Dilute 
with water or milk at home prior to obtaining 
veterinary care. Some sources recommend mineral 
oil for dilution. Emesis is contraindicated and anti 
emetic should be administered promptly. The 
mouth and oropharynx should be examined 
carefully for evidence of mucosal damage prior to 
gastric lavage. If present gastric lavage is 
contraindicated. If there is no mucosal damage, 
activated charcoal with a cathartic may be 
administered. Further care is supportive and 
includes monitoring of renal and hepatic function, 
acid-base status, and respiratory effort. Shock and 
respiratory depression are complicating factors. 
N-Acetylcysteine (NAC) and SAMe may be used to 
limit hepatic and renal toxicity.
Individuals treating dermal exposures should protect 
themselves prior to animal treatment. Polyethylene 
glycol (PEG) or glycerol is recommended for the 
initial dilution and removal of phenolic compounds 
followed by washing with a mild soap and water. 
Oil-based creams and ointments should be 
avoided as they may increase phenol absorption.
with isotonic saline and a slit lamp examination 
performed. Medications and further therapy 
depend on exam results
Pine oils (terpene alcohols) and 
turpentine (mixture of terpenes 
derived from pine oil)—
concentration of pine oil in 
disinfectants varies from 0.3% 
to 60%. Turpentine is used to 
thin oil-based paints. May also 
be found in equine hoof 
dressingsModerate to severe toxicity risk is concentration 
dependent. The oral LD50 of pine oil varies from 1 
to 2.7 mL/kg BW but much lower doses may 
result in severe toxicosis. Cats are more 
susceptible than dogs. Pine oil products are 
direct irritants to mucous membranes resulting in 
erythema in contact areas (mouth, oropharynx, 
skin).
Ingestion results in profuse salivation, abdominal 
pain, and vomiting ± blood. Systemic effects 
include respiratory depression, CNS depression, 
weakness, ataxia, and hypotension. Aspiration 
during ingestion or emesis or chemical 
pneumonitis secondary to systemic absorption 
results in pulmonary toxicity. Myoglobinuria and 
acute renal may develop with massive 
Dermal exposure causes redness and irritation.
Ocular signs include photosensitivity, 
blepharospasm, epiphora, and conjunctival and 
scleral erythemaAll oral exposures should be diluted with water. 
Induction of emesis is contraindicated, and gastric 
lavage carries a risk. Activated charcoal is not 
indicated. Further treatment is symptomatic and 
includes close monitoring of renal perfusion, 
electrolytes, and acid base status.
Affected skin should be washed well with a mild 
soap and copious amounts of water.
Ocular exposures should be irrigated for at least 15 
minutes with isotonic saline and monitored for 
further signsToxic Home and Garden Hazards for Pets ( continued )
Table VI–C

1464  Blackwell’s Five-Minute Veterinary Consult  
SOLVENTS AND ALCOHOLS
Acetone—found in nail polish 
remover, glues and rubber 
cement, paint thinner, varnish.The oral LD50 in dogs is 8 mL/kg BW but doses as 
low as 2–3 mL/kg BW may be toxic. The odor of 
acetone and presence of elevated urinary 
ketones indicate exposure. Clinical signs 
associated with a mild exposure include CNS 
depression, ataxia, and vomiting; stupor and 
coma occur with larger amounts. Hyperglycemia 
and ketonemia may be presentEmesis followed by activated charcoal with a 
cathartic has been suggested but is controversial 
due to rapid absorption of acetone and poor 
binding of activated charcoal. It may be useful if 
performed within 15–30 minutes of ingestion. 
Further therapy is symptomatic and supportive and 
may need to be continued for several days due to 
the long plasma half-life
Isopropanol—found in model 
engine fuel, deicers, windshield 
washer fluid, fuel additives, and 
varnish and stain removersThe toxic dose of 70% isopropanol is 2 mL/kg BW 
but doses as low as 0.5 mL/kg BW may be toxic. 
Signs occur rapidly, generally within 30–60 
minutes, and include vomiting ± blood, stupor, 
and ataxia which may progress to CNS and 
respiratory depression, severe hypotension, and 
coma. Mild acidosis may occurThe rapid onset of signs prevents most forms of 
decontamination. Emesis may be induced in 
asymptomatic animals if the ingestion occurred 
with 15–30 minutes. Activated charcoal is not 
recommended as it does not readily bind alcohols. 
Further treatment includes IV fluids and 
monitoring of acid-base and electrolyte status. 
Hemodialysis may be useful in animals with severe 
hypotension and coma
Methanol (methyl or wood alcohol, 
“denatured alcohol”)—found in 
windshield wiper solutions, 
antifreeze products for door 
locksThe lethal dose of oral methanol in dogs is 4–8 mL/
kg BW. Clinical signs include CNS and respiratory 
depression, ataxia, hypothermia, vomiting, and 
coma. Metabolic acidosis is rare. Blindness only 
occurs in humans and primatesTreatment is similar to isopropanol toxicosis
Ethanol—found in certain 
mouthwashes, alcohol for 
consumption (see individual 
entry), perfumes, cologne, hand 
sanitizersThe lethal dose of oral methanol in dogs is 5–8 mL/
kg BW. Clinical signs are similar to those 
associated with methanol exposures. Metabolic 
acidosis more likely than with a methanol 
exposureTreatment is similar to isopropanol toxicosisToxic Home and Garden Hazards for Pets ( continued )
Table VI–C

Canine and Feline, Seventh Edition  1465
Pain ManagementAppendix VII  Leigh A. Lamont, Kurt A. Grimm, and William J. Tranquilli
Table VII-A
Recommended parenteral opioid dosages and indications
Opioid Dose/Route/Duration Indications Comments
Butorphanol 
(injectable)Dog: 0.2–0.4 mg/kg IM, IV, or SC
Cat: 0.2–0.4 mg/kg IM, IV, or SC
Duration: 1–3 hMild to moderate pain Mild or no sedation; mild ventilatory depression
Buprenorphine 
(injectable)Dog: 0.005–0.03 mg/kg IM, IV
Cat: 0.005–0.03 mg/kg IM, IV or 
transmucosal
Duration: 3–8 h
Cat: 0.12–0.24 mg/kg SC once daily 
for up to 3 days for post-operative 
pain (SIMBADOL)
Duration: 24 hMild to moderate pain May be difficult to antagonize, onset of effect  
15–30 minutes
Morphine 
(injectable)Dog: 0.2–1.0 mg/kg IM or SC; 
0.05–0.5 mg/kg IV
Cat: 0.05–0.2 mg/kg IM or SC
Duration: 3–6 hModerate to severe pain Sedation; respiratory depression; bradycardia; nausea; 
hypothermia; dysphoria in cats without pain or with large 
dosage; rapid IV injection may cause histamine release
Methadone 
(injectable)Dog: 0.25–0.5 mg/kg IV, IM or SC
Cat: 0.1–0.25 mg/kg IV, IM or SC
Duration 3–4 hModerate to severe pain Sedation; dysphoria, vomiting, and constipation are 
reportedly less than with morphine
Hydromorphone 
(injectable)Dog: 0.05–0.2 mg/kg IM, IV, or SC
Cat: 0.05–0.2 mg/kg IM, IV, or SC
Duration: 3–6 hModerate to severe pain Similar side effects as those observed with morphine, but 
less vomiting and minimal histamine release.
May be associated with hyperthermia in cats
Fentanyl 
(injectable)Dog: 0.002–0.01 mg/kg IV
Cat: 0.001–0.005 mg/kg IV
Duration: 20–30 minModerate to severe pain; 
CRI necessary for 
long-term analgesiaSedation; respiratory depression; bradycardia; nausea; 
inadequate duration of analgesia from single IV bolus or 
IM injection
Table VII-B
Recommended dispensable opioid dosages and indications
Codeine (tablets) Dog: 1.0–2.0 mg/kg PO
Cat: 0.1–1.0 mg/kg PO
Duration: 4–8 hMild to moderate pain Minimal side effects; when dosed with acetaminophen, 
avoid in dogs with liver disease or Heinz body anemia; 
do not use in combination with acetaminophen in cats
Butorphanol (tablets) Dog: 0.5–1.0 mg/kg PO
Cat: 0.5–1.0 mg/kg PO
Duration: 2–4 hMild to moderate pain Mild or no sedation; mild ventilatory depression.
Tramadol (immediate-
release tablets)Dog: 2–10 mg/kg PO q8–12h
Cat: 2–5 mg/kg PO q8–12hMild to moderate pain Sedation, anxiety, urinary retention

1466  Blackwell’s Five-Minute Veterinary Consult  
Table VII-C
Recommended parenteral local anesthetic dosages and indications
Local Anesthetic Dose/Route/Duration Indications Comments
Lidocaine (inject able) Dog: 6–10 mg/kg infiltrate/nerve block; 
4 mg/kg epidural; 1–2mg/kg IV bolus 
followed by 0.05–0.1 mg/kg/min IV CRI
Cat: 3–5 mg/kg infiltrate/ nerve block; 
4 mg/kg epidural
Duration: 1–1.5 hModerate to 
severe painCNS and cardiac toxicity with inadvertent IV injection causing 
excessive plasma concentrations
Bupivacaine 
(injectable)Dog: 2 mg/kg infiltrate/nerve block; 1 mg/
kg epidural
Cat: 1–1.5 mg/kg infiltrate/nerve block; 
1 mg/kg epidural
Duration: 3–10 hModerate to 
severe painCardiac and CNS toxicity with inadvertent IV injection causing 
Bupivacaine (liposome 
injectable 
suspension)Dog: 5.3 mg/kg infiltrated into tissue layers 
during incisional closure of cranial 
cruciate ligament surgery (NOCITA)
Cat: 5.3 mg/kg infiltrated in each forelimb 
for peripheral nerve block for 
onychectomy (NOCITA)
Duration: 48–72 hModerate to 
excessive plasma concentrations; incisional inflammation/
discharge in small number of dogs; hyperthermia in small 
number of cats
Table VII-D
Recommended parenteral NSAID dosages and indications
NSAID Dose/Route/Duration Indications Comments
Carprofen 
(injectable)Dog: 2–4 mg/kg IV, SC q24h
Cat: 1.0 mg/kg SC only onceMild to moderate pain Primarily used perioperatively before 
switching to oral formulation; GI irritation 
and altered renal function
Meloxicam 
(injectable)Dog: 0.2 mg/kg initially IM, IV, or SC; 
0.1 mg/kg thereafter SC
Cat: 0.1–0.2 mg/kg initially IM, SC (single 
dose only per label)
Duration: 24 hMild to moderate pain Can be mixed with food; GI irritation and 
altered renal function
Ketoprofen 
(injectable)Dog: 1.0–2.0 mg/kg initially IM, IV, or SC; 
0.5–1.0 mg/kg thereafter SC
Cat: 1.0–2.0 mg/kg initially IM, IV, or SC; 
Duration: 24 hMild to moderate pain; approved in 
Canada for dogs and cats and in 
the US for horsesGI irritation and altered renal function. 
Dosing should not exceed 5 days for dogs 
and 3 days for cats
Robenacoxib 
(injectable)Dog: 2.0 mg/kg SC q24h for up to 3 days; 
PO administration as per Table VII-E 
thereafter
Cat:  2.0 mg/kg SC q24h for up to 3 daysMild to moderate postoperative 
pain and inflammationPain Management ( continued )

Canine and Feline, Seventh Edition  1467
Pain Management ( continued )
Table VII-E
Recommended dispensable NSAID dosages and indications
NSAID Dosage/Route/Duration Indications Comments
Carprofen (tablets and 
chewables)Dog: 4.4 mg/kg PO q24h or 
divided q12h
Cat: 1.0 mg/kg PO (1 dose 
only)
Duration: 12–24 hMild to moderate pain; approved for 
use in dogs with osteoarthritis or 
perioperative painToxicity associated with chronic use in cats 
due to variable half-life; may cause GI 
irritation and altered renal function in 
some patients
Deracoxib (chewable 
tablets)Dog (post-operative pain): 
3.0–4.0 mg/kg PO q24 h as 
needed for 7 days
Dog (osteoarthritis): 1–2 mg/kg 
PO q24h for long-term 
treatment over 7 days
Cat; not used
Duration: 24 hPain and inflammation associated with 
osteoarthritis. Post-operative pain 
and inflammation associated with 
orthopedic surgery in dogs with 
osteoarthritisGI irritation and altered renal function
Firocoxib (chewable 
tablets)Dog: 5 mg/kg PO q24h
Cat: not used
osteoarthritis and perioperative painGI irritation and altered renal function
Etodolac (tablets)
Grapiprant (tablets) Dog: 2 mg/kg PO q24h; cannot 
be dosed accurately in dogs 
weighing less than 3.6 kg
osteoarthritisNon-COX inhibiting-NSAID; most common 
adverse reactions are vomiting, 
diarrhea, decreased appetite, decreased 
albumin/serum protein; give on an 
empty stomach to optimize oral 
bioavailability
Aspirin (tablets) Dog: 10–25 mg/kg PO
Cat: 10–15 mg/kg PO
Duration: 8–12 h for dogs, 
24–72 h for catsMild to moderate pain and 
inflammationGI irritation and altered renal function; 
more likely at higher doses
Meloxicam (oral liquid 
suspension, tablets)Dog: 0.2 mg/kg initially PO; 
0.1 mg/kg thereafter PO
Cat: 0.1–0.2 mg/kg initially PO; 
0.05–0.1 mg/kg thereafter 
PO (reduce to minimum 
effective dose)
Duration: 24 hMild to moderate pain GI irritation and altered renal function; can 
be mixed with food. Cats should not be 
given meloxicam for > 5 days
Robenacoxib (oral 
tablets)Dog: 2.0 mg/kg PO q24h for up 
to 3 days
Cat: 1 mg/kg PO q24h for up to 
3 days
Duration: 24 hMild to moderate postoperative pain 
and inflammationGI irritation and altered renal function
Ketoprofen (tablets) Dog: 1.0–2.0 mg/kg initially 
PO; 0.5–1.0 mg/kg 
thereafter PO
Cat: 1.0–2.0 mg/kg initially PO; 
0.5–1.0 mg/kg thereafter PO
Canada for dogs and cats and in the 
US for horsesGI irritation and altered renal functions. 
Limit administration to 5 days for both 
dogs and cats
Acetaminophen 
(tablets and oral 
liquid suspension)Dog: 10–15 mg/kg PO
Cat: contraindicated
Duration (in dogs): 8–12 hMild to moderate pain; low anti-
inflammatory actionToxic to cats; often given in combination 
with codeine to dogs

1468  Blackwell’s Five-Minute Veterinary Consult  
Table VII-F
Dosages and indications for selected drugs used to treat neuropathic pain
Drug Dosage/Route Duration (PO) Comments
Ketamine (NMDA 
antagonist)Dog: 0.1–1.0 mg/kg IM, SC, or PO
Cat: 0.1–1.0 mg/kg IM or SC4–6 h
4–6 hLow doses potentiate postoperative analgesics. Do not use 
with intracranial hypertension
Amantadine (NMDA 
antagonist)Dog: 3.0–5.0 mg/kg PO
Cat: 3.0–5.0 mg/kg PO24 h
24 hUsed to potentiate or prolong analgesia. Efficacious when 
combined with an NSAID for management of osteoarthritis-
associated pain in dogs
Amitriptyline (tricyclic 
antidepressant)Dog: 1.0 mg/kg PO
Cat: 2.5–10.0 mg/cat PO12–24 h
24 hUsed to potentiate or prolong analgesia.
Gabapentin 
(antiepileptic)Dog: 2–10 mg/kg PO q8–12h; dose can 
be titrated up to 20 mg/kg q8–12h if 
necessary
Cat: 1–8 mg/kg PO q8–12h24 h
24 hUsually associated with few side effects other than sedation, 
and, occasional ataxia in cats. Has shown good results in 
human and animal studiesPain Management ( continued )
To select and administer an adjuvant analgesic properly, the veterinarian should be aware of the drug’s clinical pharmacology. The following information about the 
drug is necessary: (1) approved indication, (2) unapproved indication (e.g., as an analgesic) widely accepted in veterinary medical practice, (3) common side effects and 
potentially serious adverse effects, (4) pharmacokinetic features, and (5) specific dosing guidelines for pain.

Canine and Feline, Seventh Edition  1469
This appendix has been provided to act as a 
quick reference for supplements and 
medications commonly used to treat animals 
with joint pain and osteoarthritis (OA). The 
contraindications, precautions, and 
interactions include all of the most common 
concerns for these categories. For a 
comprehensive list of warnings, we 
recommend referring to one of the many 
veterinary drug reference that are available.The authors have also included a subjective 
evaluation of the level of evidence-based, 
peer-reviewed research that is available to 
support the use of these medications and 
supplements in clinical practice to support 
animals with osteoarthritis and inflammation:
• NONE—No evidence to support use in the 
clinical veterinary patient.
• WEAK—Evidence that shows minimal 
benefit to the veterinary patient clinically or in vitro . There may be human literature that 
could be inferred to the veterinary patient.
• MODERATE—Evidence that shows in 
vitro and/or in vivo  benefit for OA and joint 
pain.
• STRONG—Compelling evidence that 
shows benefit for OA and joint pain support 
in the clinical veterinary patient.Appendix VIII  David Dycus, Canny Fung, and Mathieu Glassman
Medications and Supplements for Osteoarthritis
Table VIII-A
Anti-inflammatories and pain medications
Category Dosage Mechanism of Action Contraindications Precautions InteractionsEvidence-Based 
Support in the 
Literature
Amitriptyline 
(tricyclic 
antidepressant 
[TCA])Dog: 1.0 mg/
kg PO
Cat: 2.5–
10.0 mg/cat 
POTCAs inhibit serotonin 
and norepinephrine 
reuptake and 
possible actions at 
opioid receptors and 
nerve transmission, 
complete MOA 
unknownPatients with renal 
or hepatic or 
thyroid or 
cardiac 
disordersMay reduce seizure 
threshold
Sedation at higher 
doses
Anticholingeric 
properties 
(constipation and 
urinary retention)
Taper when 
discontinuingConcurrent 
administration with 
monoamine 
oxidase inhibitors, 
anipryl, SSRIs due 
to potential of 
serotonin syndromeNONE—for OA 
management
Antiepileptic 
(gabapentin)Dog: 2–10 mg/kg 
PO q8–12h; 
dose can be 
titrated up to 
20 mg/kgGABA analogue, 
therapeutic action 
on neuropathic pain 
is thought to involve 
voltage-gated 
N-type calcium ion 
channels, complete 
MOA unknownPatients with renal 
or hepatic 
insufficiency 
may require less 
frequent dosing 
or lower dosesSedation at higher 
doses
Abrupt discontinuation 
can lead to severe 
rebound pain, 
tapering the dose is 
recommendedConcurrent 
administrations 
with oral antacids 
can reduce 
absorption from GI 
tractNONE—for OA 
NMDA 
antagonist 
(amantadine)Dog: 3.0–5.0 mg/
kg PO
Cat: 3.0–5.0 mg/
kg PONMDA receptor 
antagonist, 
unknown. Best used 
when combined 
with another 
analgesic such as an 
NSAIDPatients with 
hypersensitivity 
to it. Reduce 
dose in face of 
renal 
dysfunctionUse caution in patients 
with seizure 
disorders or patient 
on medications that 
lower the seizure 
threshold
GI upsetConcurrent 
with urinary 
acidifiers may 
increase excretion 
or anticholinergic 
drugs and TMS may 
enhance effects/
decrease excretionMODERATE

1470  Blackwell’s Five-Minute Veterinary Consult  
NSAIDs (various) See Table VIII-C Inhibit prostaglandin 
synthesis through 
cyclooxygenase 
enzymes. Inhibition 
of EP4 
receptor-specificNSAIDs must not 
be given with 
steroidsNSAIDs may cause 
gastric ulceration or 
upset
COX-2 selective drugs 
may interfere with 
liver function when 
used outside of 
dosage range
When switching 
NSAIDs wait 3 days 
for washout before 
starting new drug
When switching from 
aspirin to NSAID 7 
days for washout is 
requiredSteroids with NSAIDs STRONG
Opioids (various) See Tables VIII-A 
and VIII-BNatural opioid prodrug 
with suspected 
metabolism to 
active metabolites 
including morphine. 
Efficacy reflects the 
agonistic action of 
mu opioid receptorsNone Use caution in patients 
with head traumaMay decrease the 
effects of diuretics 
in patients with 
CHFMODERATEMedications and Supplements for Osteoarthritis ( continued )
Anti-inflammatories and pain medications ( continued )
NMDA = N-methyl-d-aspartate; GI = gastrointestinal; NSAID = nonsteroidal anti-inflammatory drug.
Table VIII-B
Carprofen (injectable) Dog: 2–4 mg/kg IV, SC q24h
and altered renal function.
Ketoprofen (injectable) Dog: 1.0–2.0 mg/kg initially IM, IV, or SC; 
Duration: 24 hMild to moderate pain; 
approved in Canada for dogs 
and cats and in the US for 
horsesGI irritation and altered renal function. 
and 3 days for cats.
Meloxicam (injectable) Dog: 0.2 mg/kg initially IM, IV, or SC;  
GI = gastrointestinal; NSAID = nonsteroidal anti-inflammatory drug.

Canine and Feline, Seventh Edition  1471
Table VIII-C
Recommended oral NSAID dosages and indications
Acetaminophen (tablets and oral 
Duration (in dogs): 8–12 hMild to moderate pain; low 
anti-inflammatory actionToxic to cats; often given in 
combination with codeine to dogs
Duration: 8–12 h for dogs, 24–72 h  
for catsMild to moderate pain and 
more likely at higher doses.
Not commonly used as there are 
better options available today
chewables)Dog: 4.4 mg/kg PO q24h or divided q12h
Cat: 1.0 mg/kg PO (1 dose only)
Duration: 12–24 hMild to moderate pain; 
approved for use in dogs 
with OA or perioperative 
painToxicity associated with chronic use in 
cats due to variable half-life; may 
cause GI irritation and altered renal 
function in some patients
Deracoxib (chewable tablets) Dog (postoperative pain): 3.0–4.0 mg/kg 
PO q24h as needed for 7 days
Dog (OA): 1–2 mg/kg PO q24h for 
long-term treatment over 7 days
Duration: 24 hPain and inflammation 
associated with OA. 
Post-operative pain and 
inflammation associated 
with orthopedic surgery in 
dogs with OA. Postoperative 
≥ 1.8 kgGI irritation and altered renal function
Etodolac (tablets) Dog: 10–15 mg/kg PO
Duration: 24 hMild to moderate pain Hypoproteinemia; GI irritation and 
altered renal function. Associated 
with KCS in a small number of dogs
Firocoxib (chewable tablets) Dog: 5 mg/kg PO q24h Pain and inflammation 
associated with OA and 
perioperative painGI irritation and altered renal function
Gapriprant (tablets) Dog: 2mg/kg PO q24h
Cat: up to 15mg/kg/day for 28 daysPain and inflammation 
associated with OAGI irritation. No safety evaluation in 
dogs younger than 9 months of age 
or weighing less than 3.6 kg.
FDA approved in dogs
Ketoprofen (tablets) Dog: 1.0–2.0 mg/kg initially PO; 0.5–
1.0 mg/kg thereafter PO
Cat: 1.0–2.0 mg/kg initially PO; 0.5–
approved in Canada for 
dogs and cats and in the US 
for horsesGI irritation and altered renal 
functions. Limit administration to 5 
days for both dogs and cats.
suspension, tablets)Dog: 0.2 mg/kg initially PO; 0.1 mg/kg 
Cat: 0.1–0.2 mg/kg initially PO; 0.05–
0.1 mg/kg thereafter PO (reduce to 
minimum effective dose)
Duration: 24 hMild to moderate pain GI irritation and altered renal 
function; can be mixed with food. 
Cats should not be given 
meloxicam for >5 days
Robenacoxib (oral tablets and 
injectable in some countries)Dog: 2 mg/kg SC once prior to surgery, 
1 mg/kg PO q24h for up to 12 days
Cat: 1 mg/kg PO up to 3 days in US
Duration: 24 hMild to moderate pain; not 
approved for dogs in USGI irritation and altered renal 
function.
Only FDA-approved NSAID for cats
Tepoxalin (tablets) Dog: Load 20 mg/kg, then 10 mg/kg PO 
q24hPain and inflammation 
associated with OAGI irritation. Give with food.
Caution in patients with hepatic, 
cardiac and renal dysfunction
No safety evaluation in dogs younger 
than 6 months of age or weighing 
less than 3 kgMedications and Supplements for Osteoarthritis ( continued )

Table VIII-D
Disease-Modifying Drugs (DMOADs)
Avocado Soybean 
unsaponifiables 
(ASU)300 mg/day Stimulates aggrecan production 
and restored aggrecan 
production after IL-1 β 
treatment and decreased 
MMP-3 production and 
stimulated TIMP-1 productionNone None None STRONG
Chondroitin 800 mg/day Stimulates synthesis of GAGs and 
inhibit degradative enzymesNone Large variation in products None WEAK
Glucosamine 1000 mg/day Used in the synthesis of disaccharide 
units of GAGs and proteoglycans. 
May have anti-inflammatory 
properties and may stimulate 
GAGs , proteogylcan and collagen 
synthesis, may scavenge 
oxygen-derived free radicals, 
stimulate hyaluronic acid 
synthesisNone Large variation in products None WEAK
Green-lipped mussel 
extract20–49 mg/kg/day; 4 (dogs <40 kg 
BW)–6 (dogs >40 kg BW) capsules/
day for 10 days then continuing 
with half of the loading doseMay have chondroprotective and 
anti-inflammatory propertiesNone None None STRONG
Omega-3 fatty acid Eicosapentaenoic acid (EPA), 
Dochosahexaenoic acid (DHA) 
(150–175 mg/kg of DHA and/or EPA 
daily; canineCompetes with omega-6 fatty 
acids in particular arachadonic 
acid to minimize the 
inflammatory cascade, in 
addition can cause the 
inhibition of release of 
cyclooxygenase and 
lipoxygenaseNone Use cautiously in patients 
prone to pancreatitis, 
high dosages of 
omega-3 fatty acids 
without incorporation 
of diet and daily 
exercise will lead to 
weight gainNone STRONG
glycosaminoglycans 
(Adequan)(2 mg/lb IM twice weekly for 4 weeks; 
Canine)
Off label usage for SC route, for felines, 
and for monthly maintenanceNot completely known suspected to 
inhibit serine proteinases, 
prostaglandin E2 synthesis, and 
metalloproteases. May stimulate 
synthesis of protein, collagen, 
proteoglycan, and hyaluronic acidNone Use caution in patients 
with underlying clotting 
or platelet pathologyNone STRONG
T-Relief Dogs: 1–3 tablets PO q8h
Newborn puppies: ½ tablet PO q24h
Weaned puppies: 1 tablet PO q8h
Cats: 1 tablet PO q8hUnknown; homeopathic 
ingredients including arnica 
Montana and belladonna to 
help with minor injuriesNone None None WEAK
GAGs = glycosaminoglycans; MMP = matrix metalloproteinsases; IL-1 = interleukin-1; TIMP = tissue inhibitors of metalloproteinase.Medications and Supplements for Osteoarthritis
1472

Canine and Feline, Seventh Edition  1473
 GLOSSARY OF TERMINOLOGY 
FOR SEIZURES AND EPILEPTIC 
DISORDERS
There is no formally approved classification 
system for seizures or epilepsy in veterinary 
medicine and authors proposing such systems 
in the past have largely adapted human 
classification schemes (1–5). This proposed 
glossary is no different and is based mainly on 
publications sanctioned by the International 
League Against Epilepsy (ILAE) (6–11). 
Terms have been added, changed or elimi-
nated to better reflect the seizure types seen in 
veterinary patients and the challenges 
inherent with the interpretation of such 
events in animals. This glossary is adapted 
from a more detailed proposal of terminology 
for veterinary patients (12), and interested 
readers are referred to this work for more 
details on seizure description and semiology, 
background on ILAE classification and 
adaptations for animals, and rationale for the 
currently proposed terms.
 GENERAL TERMS AND DEFINITIONS
Seizure:  a discrete episode suspected to be 
epileptic in origin. Synonym: ictus.
Epileptic seizure:  manifestation(s) of 
excessive and/or hypersynchronous activity of 
neurons in the brain; usually self-limiting.
Epilepsy:  a chronic neurologic condition 
characterized by recurrent seizures; has an 
intracranial origin.
Focal seizure:  a seizure whose initial signs 
indicate, or are consistent with, initial 
activation of only part of one cerebral 
hemisphere. Synonym: partial.
Generalized seizure:  a seizure whose initial 
signs indicate, or are consistent with, more 
than minimal involvement of both cerebral 
hemispheres.
 CLASSIFICATION OF EPILEPTIC 
SEIZURES
1. Motor Seizures:  involving somatic 
musculature in any form. May consist of an 
increase (positive) or decrease (negative) in 
muscle contraction to produce a movement.
1A. Elementary Motor:  a single type of 
contraction of a muscle or group of muscles 
that is usually stereotyped.
• T onic : a sustained increase in muscle 
contraction lasting a few seconds to minutes.
• Myoclonic:  sudden, brief (< 100 ms), 
involuntary single or multiple contractions of 
muscles or muscle groups of variable 
topography (axial, proximal limb, distal limb, 
facial).
◦ Clonic:  myoclonus that is regularly 
repetitive, involves the same muscle groups, 
at a frequency of approximately 2–3 per 
second, and is prolonged.• T onic-clonic:  a sequence consisting of a 
tonic followed by a clonic phase.
◦ Generalized tonic-clonic seizure:  
bilateral symmetric tonic contraction and 
then bilateral clonic contractions of somatic 
muscles, usually associated with autonomic 
phenomena and loss of consciousness. 
Synonyms: grand mal seizure, bilateral 
tonic-clonic seizure, major motor seizure.
• Atonic:  sudden loss or diminution of 
muscle tone without an apparent preceding 
myoclonic or tonic event lasting greater than 
1–2 seconds and involving the head, trunk, 
jaw or limb musculature.
• Astatic:  loss of erect posture that results 
from an atonic, myoclonic or tonic mecha-
nism. Synonym: drop attack.
1B. Automatism:  a more or less coordinated, 
repetitive, motor activity usually occurring 
when cognition is impaired. Often resembles 
a voluntary movement. Examples might 
include chewing, licking, aimless running, or 
vocal utterances (e.g., barking, meowing, 
whining or growling).
2. Non-motor Seizures
Aura:  an ictal phenomenon that may precede 
an observable seizure or if occurring alone, 
constitutes a sensory seizure.
Sensory seizure:  a perceptual experience not 
caused by appropriate stimuli in the external 
world.
Note: Although sensory seizures almost 
certainly occur in animals, documenting 
their existence is obviously very difficult 
without the ability of the patient to describe 
sensory phenomena. Therefore, we are left 
to observe the behavior that the suspected 
sensory seizure produces. Some potential 
sensory phenomena include visual events 
(e.g., flashing or flickering lights, or other 
objects or patterns; the animal may bite or 
snap in response [“fly biting”]), somatosen-
sory events (tingling, numbness or 
electric-shock sensations; the animal may 
bite or lick itself or run frantically during 
episode), auditory, olfactory, gustatory and 
affective events (e.g., fear, depression, joy or 
anger; the animal may become aggressive 
towards people or other animals).
Dyscognitive seizure:  events in which 
disturbance of cognition is the predominant 
or most apparent feature.
Note: In the ILAE glossary, cognition is 
composed of perception, attention, 
emotion, memory and executive function 
(which includes decision making and 
initiation of motor activity) (8). In animals, 
without a description from the patient it 
may again be difficult to prove that certain 
dyscognitive seizure types exist or differenti-
ate them from sensory seizures. However, 
certain examples (e.g., events where animals suddenly stop what they are doing and stare 
into space, often with a lack of appropriate 
responsiveness to external stimuli [“behav-
ioral arrest”]) might be best classified here.
3. Autonomic Seizures:  an objectively 
documented and distinct alteration of 
autonomic nervous system function involving 
cardiovascular, pupillary, gastrointestinal, 
sudomotor, vasomotor, and thermoregulatory 
functions.
 MODIFIERS AND DESCRIPTORS 
OF SEIZURE TIMING
Duration:  time between the beginning of 
initial seizure manifestations and the cessation 
of observed seizure activity. Does not include 
prodrome or postictal states but might 
include aura.
Cluster seizures:  two or more seizures within 
a 24-hour period. Synonyms: acute repetitive 
seizures, serial seizures
Status epilepticus:  1) a seizure that persists 
for greater than 5 minutes or 2) recurrent 
seizures without interictal resumption of 
baseline central nervous system function.
Prodrome:  a pre-ictal phenomenon. A 
subjective or objective clinical alteration (e.g., 
agitation, attention-seeking) that heralds the 
onset of an epileptic seizure but does not 
form part of it.
Note: It may be quite challenging or 
impossible to differentiate a prodrome 
(pre-ictal period) from an aura (start of ictus) 
in many veterinary patients although 
videotaping of the episodes, close observation 
and/or ictal electroencephalography may be 
helpful in this regard.
Postictal phenomenon:  a transient clinical 
abnormality of central nervous system 
function that appears or becomes accentuated 
when clinical signs of the ictus have ended. 
May manifest as impaired mentation, altered 
behavior or motor or sensory deficits.
Provocative factor:  transient and sporadic 
endogenous or exogenous element capable of 
augmenting seizure incidence in animals with 
chronic epilepsy or evoking seizures in 
susceptible individuals without epilepsy.
• Reactive:  occurring in association with 
transient systemic perturbation or illness such 
as some metabolic conditions (e.g., hypogly-
cemia, electrolyte disorders) or intoxications.
• Reflex:  objectively and consistently demon -
strated to be evoked by a specific afferent 
stimulus or by activity of the patient. Examples 
include stimuli such as light flashes, certain 
noises or startling and activities such as specific 
motor movements or more complex behaviors.
 CLASSIFICATION OF EPILEPSY
Epilepsy is defined here as a chronic

Epilepsy is defined here as a chronic 
neurologic disorder that causes recurrent 
seizure activity, and that has an intracranial Glossary of Terminology for Seizures and Epileptic DisordersAppendix IX  Christopher L. Mariani

1474  Blackwell’s Five-Minute Veterinary Consult  
etiology. As stated by the ILAE Classification 
Core Group in 2006, “the diagnosis of 
epilepsy implies a persistent epileptogenic 
abnormality of the brain that is able to 
spontaneously generate paroxysmal activity. 
This is in contrast to a brain that has an acute 
seizure as a natural response to a transient 
insult or loss of homeostasis” (10). Thus, 
seizures caused by extracranial disorders such 
as metabolic conditions (e.g., hypoglycemia, 
electrolyte abnormalities) or toxins are not 
considered to be epilepsy, even when 
repetitive seizures occur over time (e.g., with 
hypoglycemia secondary to an insulinoma). 
These seizures are termed reactive seizures (see 
definition under “provocative factor” above). 
Note however that such a disorder might 
secondarily cause structural damage to a 
previously normal brain (e.g., through 
necrosis or excitotoxicity) and result in true 
epilepsy. An explanation of the term 
“idiopathic epilepsy” is also warranted here, as 
veterinarians use the word “idiopathic” in 
various ways. Some use this term to imply 
epilepsy of genetic or heritable origin (as it 
was originally intended for use in humans), 
while others use “idiopathic” to mean “cause 
unknown.” The following classification is 
proposed to replace those previously used in 
veterinary medicine and has been adapted 
from a 2010 ILAE report (11).
Genetic epilepsy:  Epilepsy as a direct 
result of a known or strongly suspected 
genetic defect or defects in which seizures 
are the core sign of the disorder. Generally, 
genetic epilepsies have no identifiable 
structural brain lesion or other neurologic 
signs, and have an age-dependent onset. 
Synonyms: Primary, inherited, idiopathic 
(for some).Structural epilepsy:  Epilepsy as a result of 
one or more identifiable structural lesions of 
the brain. Synonyms: Symptomatic, 
secondary. Structural epilepsies include 
disorders such as brain tumors, encephalitis, 
and cerebrovascular accidents. Note that some 
disorders that may have a genetic cause or 
that are strongly heritable may still be best 
classified here; these include anomalous 
disorders such as hydrocephalus, lissenceph-
aly, degenerative disorders such as ceroid 
lipofuscinosis, and others.
Unknown epilepsy:  The underlying cause of 
the epilepsy is unknown. This may be the 
result of a subtle structural lesion that is 
undetectable with currently available 
diagnostic technologies or an as yet unrecog-
nized genetic disorder. Synonyms: 
Cryptogenic, probably symptomatic, 
idiopathic (for some).
 1 Berendt M, Gram L. Epilepsy and seizure 
classification in 63 dogs: A reappraisal of 
veterinary epilepsy terminology. J Vet 
Intern Med 1999;13:14–20.
 2 March PA. Seizures: Classification, 
etiologies, and pathophysiology. Clin Tech 
Small Anim Pract 1998;13:119–131.
 3 Podell M. Seizures in dogs. Vet Clin 
North Am Small Anim Pract 
1996;26:779–809.
 4 Podell M. Seizures. In: Platt SR, Olby NJ, 
editors. BSAVA manual of canine and 
feline neurology. Gloucester: British Small 
Animal Veterinary Association; 2013, 
pp. 117–135.
 5 Podell M, Fenner WR, Powers JD. Seizure 
classification in dogs from a nonreferral-
based population. J Am Vet Med Assoc 
1995;206:1721–1728.  6 Proposal for revised classification of epilepsies 
and epileptic syndromes. Commission 
on Classification and Terminology of the 
International League Against Epilepsy. 
Epilepsia 1989;30: 389–399.
  7 Blume WT, Luders HO, Mizrahi E, 
Tassinari C, van Emde Boas W, Engel J, 
Jr. Glossary of descriptive terminology 
for ictal semiology: Report of the ILAE 
Task Force on Classification and 
Terminology. Epilepsia 
2001;42:1212–1218.
  8 Engel J, Jr. A proposed diagnostic 
scheme for people with epileptic seizures 
and with epilepsy: Report of the ILAE 
2001;42:796–803.
  9 Fisher RS, van Emde Boas W, Blume W, 
Elger C, Genton P , Lee P , et al. Epileptic 
seizures and epilepsy: Definitions 
proposed by the International League 
Against Epilepsy (ILAE) and the 
International Bureau for Epilepsy (IBE). 
Epilepsia 2005;46:470–472.
 10 Engel J, Jr. Report of the ILAE classifica-
tion core group. Epilepsia 
2006;47:1558–1568.
 11 Berg AT, Berkovic SF , Brodie MJ, 
Buchhalter J, Cross JH, van Emde Boas 
W, et al. Revised terminology and 
concepts for organization of seizures and 
epilepsies: Report of the ILAE 
Commission on Classification and 
Terminology, 2005–2009. Epilepsia 
2010;51:676–685.
 12 Mariani CL. Terminology and classifica-
tion of seizures and epilepsy in veterinary 
patients. Top Companion Anim Med 
2013;28:34–41.

Canine and Feline, Seventh Edition  1475
Common Procedures and Testing Protocols Appendix X

1476  Blackwell’s Five-Minute Veterinary Consult  
Abdominocentesis and Fluid Analysis
  BASICS
TYPE OF PROCEDURE
Diagnostic sample collection.
PROCEDURE EXPLANATION 
AND RELATED PHYSIOLOGY
• Abdominocentesis is the percutaneous 
removal of peritoneal fluid for diagnostic and/
or therapeutic purposes.
• Characterization of abdominal fluid may 
help determine primary disease process or 
pathophysiologic mechanism responsible for 
• Blind abdominocentesis is easily performed 
when a large amount of fluid is present; 
ultrasound-guided abdominocentesis is useful 
when fluid volume is limited or localized.
• Diagnostic peritoneal lavage (DPL) is most 
often considered if abdominocentesis has 
failed to yield any fluid and undiagnosed 
intra-abdominal disease is suspected.
• Therapeutic abdominocentesis may 
improve quality of life in conjunction with 
medical management of chronic ascites.
INDICATIONS
• Peritoneal fluid suspected based on physical 
examination (abdominal distention, fluid 
wave) or diagnostic imaging.
• Blunt or penetrating abdominal trauma 
(e.g., dog bite, gunshot wound, motor 
vehicular accident).
• Suspicion of ruptured bowel, peritonitis, or 
postoperative GI dehiscence.
• Acute abdominal pain.
• Shock without apparent cause.
• DPL—with suspicion of undiagnosed 
intra-abdominal disease in face of negative 
• Therapeutic abdominocentesis—when 
increased intra-abdominal pressure causes 
respiratory distress, decreased blood flow to 
visceral organs, or discomfort.
• Abdominocentesis should be performed with 
caution or is contraindicated in presence of:
◦ Dilated hollow abdominal viscus 
(stomach and intestines), generalized ileus.
◦ Organomegaly.
◦ An enlarged uterus because of pregnancy or 
pyometra.
◦ Coagulopathy, thrombocytopenia.
• An uncharacterized large intra-abdominal 
mass is contraindication for blind 
• Avoid DPL if diaphragmatic hernia 
• Hemorrhage from a punctured vessel or 
lacerated abdominal organ.
• Perforation of a hollow viscus (bowel, bladder) and iatrogenic peritonitis.
• Spread of infection, especially from a 
localized lesion (e.g., abscess, pyometra).
• Tearing of a fenestrated over-the-needle 
catheter in the abdomen during removal.
• Large-volume abdominocentesis may cause 
rapid fluid shifts and electrolyte changes:
◦ Avoid removing large volumes from 
animals that have serum albumin of ≤2 g/dL.
• In addition to the above, DPL may result in 
subcutaneous hematoma or leakage of lavage 
fluid.
• Abdominocentesis is a minimally invasive 
diagnostic procedure that is generally easy to 
perform and associated with minimal risk and 
• Abdominocentesis is usually performed in 
awake patients, but sedation and/or analgesia 
BODY SYSTEMS ASSESSED
• Urinary.
• Vascular (as with hemoabdomen).
  PROCEDURE
PATIENT PREPARATION
Pre-Procedure Medication or 
Preparation
Consider emptying a distended urinary 
bladder prior to abdominocentesis or DPL.
Anesthesia or Sedation
Patients should be restrained either manually 
or with sedation/analgesia to prevent 
unwanted motion that could result in 
complications. Prior to drug administration, 
consider patient’s general and cardio  vascular 
condition (e.g., shock) and procedure being 
performed (sedation and local analgesia 
almost always indicated for DPL).
Patient Positioning
Patient in left lateral recumbency (to prevent 
splenic puncture) or can remain standing to 
improve gravity-dependent fluid retrieval. 
Patient positioning may be altered based on 
visualization of fluid using ultrasound 
guidance.
Patient Monitoring
Blood pressure, pulse oximetry, and heart 
rate/ECG should be monitored as indicated 
by patient’s clinical status. Patients should be 
monitored for signs of pain or discomfort.
Equipment or Supplies
• Clippers.
• Surgical scrub.
• Sterile gloves.
• Syringes of various sizes (3, 5, or 10 mL).• 2% Lidocaine (injectable).
• Glass slides.
• EDTA and serum tubes and culturettes.
For Abdominocentesis
• Hypodermic needle: 18- through 22-gauge, 
1- to 1½-inch or over-the-needle IV catheter 
of similar size. Butterfly catheters may be 
used in small or thin patients.
• Consider addition of fenestrations in large 
gauge (14–18 gauge) over-the-needle 
catheters using a sterile scalpel blade. 
Fenestrations should be small and smooth 
and should not be directly opposite each 
other, as this may lead to catheter weakening 
and possible kinking or tearing within 
abdomen.
• Optional: extension set.
• For therapeutic abdominocentesis, a 
three-way stopcock, 20- to 60-mL syringe, 
and collection vessel.
For DPL
• A commercially available peritoneal dialysis 
catheter or alternatively a 20- to 14-gauge, 
over-the-needle, 1–2 inch IV catheter, 
fenestrated as described previously.
• A bag of warmed sterile isotonic saline 
solution with an administration set.
• 3- to 12-mL syringes.
• A three-way stopcock attached to an 
extension set (optional).
TECHNIQUE
Closed or Open Needle 
• Abdominocentesis site is just caudal to 
umbilicus, on ventral midline or slightly 
lateral to the right (2–3 cm in mid-sized 
dogs). In a standing patient, site is at most 
dependent part of abdomen.
• A 10 × 10 cm area should be clipped, and 
skin prepared aseptically.
• Lidocaine 2% local anesthetic may be 
infused at the abdominocentesis site.
• Needle is inserted through skin and 
abdominal wall; if using an over-the-needle 
catheter, catheter is fed off stylet once in the 
abdomen (typically fluid visible in hub):
◦ If needle or catheter is not attached to a 
syringe, collect the fluid into a sterile tube 
as it drips from the hub (this technique may 
introduce air into abdomen).
◦ If needle or catheter is attached to syringe 
or extension set and syringe, apply gentle 
suction; vigorous suction may result in 
false-negative result.
• Collect fluid aseptically, perform cytologic 
analysis, bacteriologic culture, other 
diagnostics as indicated.
• For therapeutic abdominocentesis, 
extension set and 3-way stopcock are 
mounted on needle or catheter and attached 
to a syringe.

Canine and Feline, Seventh Edition  1477
• When using an over-the-needle catheter 
with added fenestrations, take care to remove 
it completely by gently rotating it or 
dissecting it from subcutaneous tissue.
Four-Quadrant Abdominocentesis
• Divide ventral surface of abdomen into 4 
quadrants by an imaginary line that bisects 
linea alba and through the umbilicus.
• Wide surgical prep centered at umbilicus.
• Insert needles, one at a time, in each 
quadrant until fluid is retrieved.
• Fluid should flow through needle into 
sampling tubes.
• False-negative results more likely if suction 
applied.
Ultrasound-Guided Abdominocentesis
• Locate small volume or localized effusion 
with ultrasonography.
• Clip hair on a 10 × 10 cm area and prepare 
aseptically.
• Mount needle on syringe or extension set 
attached to syringe, insert under ultrasound 
guidance into pocket of fluid and gently 
aspirate.
Diagnostic Peritoneal Lavage (Closed 
Technique)
• Consider imaging (abdominal radiographs, 
CT, or ultrasound) prior to DPL as this 
procedure will alter results.
• DPL site is 1–3 cm caudal to umbilicus, on 
midline or just right from midline.
• Infiltrate skin and abdominal wall with 
local anesthetic at puncture site.
• Make a stab incision through skin with a 
number 11 scalpel blade at site of local 
anesthetic infusion.
• Introduce catheter with stylet into 
abdomen through stab incision.
• Slide catheter off stylet dorsocaudally into 
abdomen.
• Once catheter is in abdomen, attach syringe 
and aspirate gently. If fluid is retrieved, there 
is no need to proceed with lavage.
• In the absence of fluid, infuse 20–22 mL/
kg of warm sterile 0.9% saline solution 
through catheter using an IV infusion set 
with rapid gravity flow.
• After completing infusion, have patient 
walk around (if able) or roll patient gently 
from side to side to disperse fluid, taking care 
not to dislodge catheter.
• Aspirate catheter gently with a syringe to 
remove fluid sample. Most often, only a 
small portion of instilled fluid is retrieved; 
remaining fluid will be reabsorbed by 
• Collect lavage fluid aseptically and analyze.
SAMPLE HANDLING
• Inspect fluid macroscopically for clarity and 
color.
• Divide fluid into aliquots:◦ EDTA tube for cytologic evaluation, 
including red blood cell and nucleated cell 
counts and differential ( not for culture).
◦ A serum tube for biochemical analysis as 
indicated (may need concurrent analysis on 
peripheral blood; see below).
◦ A culturette or an additive-free glass tube, 
for aerobic and anaerobic bacterial culture, 
depending on laboratory preference.
• Determine specific gravity and total solids 
(TS) by refractometry.
• Direct microscopic cytologic evaluation: 
smear small drop of fluid across a slide, 
air-dry, and apply Romanovsky-type stain 
(Diff-Quik, Hema III, Giemsa, or Wright 
stain). For hypocellular fluids (2,000–50,000 
cells/μL), a drop from the resuspended pellet 
of a centrifuged sample can be evaluated. 
Cytospin preparation may be necessary for 
very hypocellular (<2,000 cells/ μL) samples.
• Measure packed cell volume (PCV) and TS 
of hemorrhagic effusions. Consider the 
following paired biochemical tests based on 
differential diagnoses:
◦ Uroabdomen: creatinine, potassium.
◦ Bile peritonitis: bilirubin.
◦ Pancreatitis: lipase, amylase, cPLI.
◦ Chyloabdomen: triglycerides, cholesterol.
◦ Septic peritonitis: glucose, lactate.
◦ FIP: protein electrophoresis.
APPROPRIATE AFTERCARE
Post-Procedure Patient Monitoring
Usually none, but should be tailored to 
patient’s general condition (e.g., shock, pain).
None
Dietary Modification
None
Medication Requirements
Analgesia might be required.
Restrictions on Activity
Cage rest, as needed, depending on patient’s 
Anticipated Recovery Tme
N/A
  INTERPRETATION
NORMAL FINDINGS OR RANGE
• Absence of free intra-abdominal fluid.
• In normal dogs, lavage fluid WBC count is 
<500–1,000 cells/ μL.
• Postsurgery lavage fluid WBC count can be 
up to 10,000 cells/ μL. Cytologic 
characteristics are more meaningful than cell 
count in differentiating septic vs. nonseptic 
peritonitis in these cases.
ABNORMAL VALUES
• Presence of free intra-abdominal fluid.• Lavage fluid with >1,000 WBCs/ μL or that 
is grossly abnormal (e.g., hemorrhagic, 
greenish, cloudy, purulent).
• Depending on macroscopic appearance, 
specific gravity, protein content, cellularity, 
and cytologic findings, abdominal effusion is 
classified as pure transudate, modified 
transudate, and exudate (septic and 
nonseptic). Its etiology can sometimes be 
Additional Results for Specific 
Conditions
• Chyloabdomen—concentration of 
abdominal fluid triglycerides higher than 
serum triglyceride concentration; triglyceride 
concentration often >100 mg/dL.
• FIP—abdominal fluid albumin/globulin 
ratio <0.8 suggests FIP .
• Hemoabdomen—if PCV of abdominal 
fluid is greater than peripheral PCV, organ 
or large vessel laceration or disruption is 
suspected. Hemodilution may occur in cases 
of uroabdomen with concurrent 
hemorrhage or after DPL. Because DPL 
fluid cannot be compared with peripheral 
PCV, a PCV >5% in DPL fluid is indicative 
of hemorrhage.
• Uroabdomen—abdominal fluid creatinine 
concentration higher than serum creatinine 
concentration (>2:1), potassium concentration 
in effusion greater than serum potassium 
(>1.4:1). BUN is not reliable for diagnosis of 
uroabdomen (rapidly equilibrates across 
peritoneum).
• Bile peritonitis—fluid bilirubin concentra -
tion higher than that of serum, extra- or 
intracellular bile pigment usually found on 
cytologic examination.
• Pancreatitis—higher fluid amylase and 
lipase concentrations than serum suggest 
pancreatitis. Peritoneal fluid canine-specific 
pancreatic lipase (cPL) concentration is very 
sensitive in dogs as an aid in diagnosis of 
acute pancreatitis.
• Peritonitis—>1,000 WBCs/ μL in lavage 
fluid.
• Septic peritonitis—intracellular bacteria (± 
extracellular bacteria), presence of degenerate 
neutrophils are diagnostic for septic effusion. 
Additionally, the fluid lactate concentration is 
higher in septic vs. nonseptic effusions. In 
dogs, a fluid lactate concentration >2.5–4 
mmol/L and a blood-to-fluid lactate 
difference of >2 mmol/L has good sensitivity 
and specificity for diagnosing septic effusion. 
This may be less reliable in cats. A blood-to-
fluid glucose difference of >37 mg/dL is 
sensitive and specific for septic peritoneal 
effusion in dogs and cats.
• Eosinophilic effusion—>10% eosinophils 
in fluid.
• Aberrant cestodiasis—the presence of 
Mesocestoides  spp.(continued)  Abdominocentesis and Fluid Analysis

1478  Blackwell’s Five-Minute Veterinary Consult  
CRITICAL VALUES
• After adequate cardiovascular resuscitation, 
the following conditions need immediate 
attention and might require exploratory 
celiotomy:
◦ Septic peritonitis.
◦ Uroabdomen.
◦ Bile peritonitis.
◦ Hemoabdomen.
INTERFERING FACTORS
Drugs That May Alter Results 
of the Procedure
Avoid sedative agents that induce spleno  - 
megaly.
Conditions That May Interfere 
with Performing the Procedure
• If there is abdominal distention, 
differentiate between organomegaly, 
intra-abdominal fat, and fluid accumulation 
before abdominocentesis.
• Adhesions from previous surgeries may 
interfere with DPL.
• Insufficient fluid quantity for technique 
used.
• Flocculent or fibrinous fluid.
• Fluid localized in a difficult to access space 
(e.g., cranial to liver).
• Negative abdominocentesis is possible in a 
patient with an acute disease process. Repeat 
imaging and/or abdominocentesis can be 
considered if indicated based on clinical signs 
and increased suspicion of intra-abdominal 
disease.
• A negative abdominocentesis is possible in a 
patient with severe dehydration or hypo -
volemia; repeat imaging and abdominocentesis 
following IV fluid resuscitation.
Procedure Techniques or Handling That 
May Alter Results
• Vigorous suction can result in needle or 
catheter blockage by omentum or viscera.
• In the absence of coagulopathy, blood from 
traumatic sampling will usually clot when 
exposed to an artificial surface, whereas 
peritoneal effusion will not.
• Degenerate neutrophils and intracellular 
bacteria are signs of septic peritonitis; while 
bacteria and debris may be present if a loop of bowel is aspirated, typically degenerate 
neutrophils are absent.
Influence of Signalment on Performing 
and Interpreting the Procedure
Species
None
Breed
None
Age
None
Gender
None
Pregnancy
Relative contraindication because of an 
enlarged uterus.
Clinical Perspective
• Many different diseases may manifest with 
peritoneal effusion; cytologic and fluid 
analysis are indicated for every effusion.
• Use of a fenestrated catheter vs. a needle 
may increase likelihood of fluid retrieval.
• DPL may provide superior diagnostic 
accuracy but is much more time intensive to 
perform, and samples are diluted.
ANCILLARY TESTS
• CBC, serum biochemistry, and urinalysis.
• Abdominal ultrasonography: assess 
parenchymal integrity, identify small fluid 
volume.
• Any additional testing to determine 
primary etiology of abdominal effusion 
(nonexhaustive list; see Ascites):
◦ Thoracic radiography, echocardiogram, 
and ECG (right-sided heart failure, 
pericardial effusion, metastatic neoplasia).
◦ Excretory urography or contrast 
cystourethrogram if uroabdomen is 
◦ Serum bile acids if hepatic failure/portal 
SYNONYMS
• Abdominal tap.SEE ALSO
Ascites.
• DPL = diagnostic peritoneal lavage.
• TS = total solids.
Bonczynski JJ, Ludwig LL, Barton LJ, et al. 
Comparison of peritoneal fluid and 
peripheral blood pH, bicarbonate, glucose, 
and lactate concentration as a diagnostic 
tool for septic peritonitis in dogs and cats. 
Vet Surg 2003; 32:161–166.
Chartier MA, Hill SL, Sunico S, et al. 
Pancreas-specific lipase concentrations and 
amylase and lipase activities in the 
peritoneal fluid of dogs with suspected 
peritonitis. Vet J 2014, 201: 385–389.
Connally HE. Cytology and fluid analysis of 
the acute abdomen. Clin Tech Small Anim 
Pract 2003, 18:39–44.
Jandry KE. Abdominocentesis and diagnostic 
peritoneal lavage. In: Silverstein D, Hopper 
K, eds., Small Animal Critical Care 
Medicine, 2nd ed. St. Louis, MO: Elsevier, 
2015, pp1036–1039.
Koenig A, Verlander LL. Usefulness of whole 
blood, plasma, peritoneal fluid, and peritoneal 
fluid supernatant glucose concentrations 
obtained by a veterinary POC glucometer to 
identify septic peritonitis in dogs with 
peritoneal effusion. J Am Vet Med Assoc 
2015, 247:1027–1032.
Levin GM, Bonczynski JJ, Ludwig LL, et al. 
Lactate as a diagnostic test for septic 
peritoneal effusions in dogs and cats. J Am 
Anim Hosp Assoc 2004; 40:364371.
Martiny P , Goggs R. Biomarker guided 
diagnosis of septic peritonitis in dogs. Front 
Vet Sci 2019, 6:208.
Schmiedt C, Tobias, KM, Otto CM. 
Evaluation of abdominal fluid: peripheral 
blood creatinine and potassium ratios for 
diagnosis of uroperitoneum in dogs. J Vet 
Emerg Crit Care 2001, 11:275–280.
Author  Kim Slensky
Consulting Editor  Benjamin M. Brainard
acknowledge the prior contribution of Karine 
Savary Bataille.Abdominocentesis and Fluid Analysis  (continued)

Canine and Feline, Seventh Edition  1479
Arthrocentesis With Synovial Fluid Analysis
  BASICS
Synovial fluid is normally a clear, viscous fluid 
essential in the mechanical function of joints. 
Synovial fluid analysis is integral in the 
diagnosis and characterization of joint disease 
in canine and feline patients. Joint disease can 
involve one or more joints and can be due to 
infectious, inflammatory or noninflammatory 
etiologies. Synovial fluid analysis can differ­
entiate inflammatory vs. noninflammatory 
arthropathies and can aid in determination of 
the underlying cause. Arthrocentesis is a safe, 
quick, and relatively easy procedure to 
perform in most clinical settings and involves 
fine­needle aspiration of joint fluid. The 
equipment needed is minimal and 
inexpensive, and the techniques are not 
difficult to learn, requiring only basic 
knowledge of joint anatomy.
• Joint pain or effusion.
• Lameness/stiffness or gait abnormality.
• Fever of unknown origin.
• Undefined lethargy or nonspecific pain.
• No absolute contraindications.
• Caution with coagulopathy.
• Caution with severe thrombocytopenia 
(<20,000/ μL).
• Sedation ­associated complications.
• Iatrogenic joint infection.
• Hemarthrosis.
• Patients will need to be sedated.
• Patients will need to have multiple joints 
shaved.
  PROCEDURE
None
• Adequate sedation required.
• Opioids for pain control:
◦ Hydromorphone 0.05–0.1 mg/kg IM or IV.
◦ Methadone 0.1–0.3 mg/kg IM or IV.
◦ Fentanyl 3–5 μg/kg IV.• Dexmedetomidine 3–10 μg/kg IM or IV to 
effect.
• General anesthesia often not required.
Lateral recumbency.
Standard for sedation protocol.
• Surgical prep—chlorhexidine scrub/
betadine scrub.
• Alcohol prep.
• Sterile hypodermic needles.
• 22­Gauge 1 ­inch needles (for cats and small 
dogs):
◦ Most commonly used.
• 22­Gauge 1½ ­inch needles (may be needed 
for large dogs).
• Sterile 3 ­mL syringes.
• A culturette or culture transport vial.
• Glass microscope slides.
• EDTA tubes.
TECHNIQUE
• Prior to starting the procedure, have all 
equipment in place and familiarize yourself with 
the anatomy of the selected joint (Figures 1–5).
• It is recommended to sample three or more 
joints.
• Clip overlying hair and aseptically prepare 
the chosen joint.
• It is essential to appropriately prepare sites 
to avoid iatrogenic joint infection.
• Don sterile gloves.
• An assistant opens the syringe and needles, 
aseptically placing them on the sterile field. 
The needle should be mounted on the syringe.
• Flex the joint using the nondominant hand 
(now nonsterile) and palpate the appropriate 
landmarks for the specific joint to be tapped 
with the dominant hand (sterile).
• Holding the syringe, pass the needle 
through the skin, joint capsule, and synovial 
membrane, into the joint cavity. Avoid the 
articular cartilage. If bone is encountered, 
pull back slightly and redirect the needle into 
the joint space.
• Gently aspirate. Unless the joint is severely 
distended, only a few drops of fluid may be 
obtained in the hub of the needle. As soon as 
fluid appears in the hub of the needle, release 
negative pressure and remove the needle from 
the joint. If the joint is very distended, a larger 
volume of fluid may be removed from the joint 
space. If blood is seen in the hub of the needle 
at any point in the procedure, immediately 
release pressure and remove the needle.
• Ensure that the negative pressure (the 
plunger) is released prior to withdrawing the 
syringe from the point to avoid contamination 
of the fluid with peripheral blood.
• A large amount of blood makes cytologic 
evaluation too difficult, and tapping a new joint space is advisable. A small amount of 
blood may be in the joint space as part of the 
Note: The following discussion about 
individual joints is presented in order of 
increasing difficulty:
Carpal Joint
• With the nondominant hand, flex the joint 
to achieve a maximum amount of open joint 
space.
• Palpate the space between the radius and 
proximal carpal bones, the proximal carpal 
bones and distal carpal bones, and the carpal 
and metacarpal bones.
• The radiocarpal joint is the most common 
joint space to tap due to the larger space.
• Identify and avoid the dorsal common 
digital artery and accessory cephalic vein.
• Holding the syringe, insert the needle from 
the cranial surface through the skin and joint 
capsule and into the joint space.
Stifle Joint
• Due to its large size, this joint is frequently 
aspirated.
• The stifle may be approached from either 
the medial or lateral aspect.
Figure 1 .
Schematic representation of landmarks for the 
carpal joint.

1480  Blackwell’s Five-Minute Veterinary Consult  
• Flex the stifle joint to open the joint space.
• Insert the needle from the cranial aspect, 
lateral or medial to the patellar ligament. The 
needle should enter the joint approximately 
halfway between the patella and tibial tuberosity.
• Direct the needle caudally and obliquely 
toward the intercondylar space.
• It may be helpful to apply digital pressure to 
the opposite side of the patellar ligament to 
cause joint fluid to collect toward the approach. A fat pad is present that may interfere with 
obtaining fluid. If fluid is not obtained initially, 
back up the needle, redirect, and aspirate.
Tarsal Joint
• T wo small joint spaces can be tapped in the 
tarsus.
• One approach is to flex the joint slightly 
and palpate the cranial space between the 
tibia and tibiotarsal bone. Insert the needle 
from the cranial and lateral aspect and direct 
it medially. This joint is shallow and the 
needle will not be advanced very far.
• The second approach is from the distal aspect 
and is accomplished by flexing the tarsal joint 
more fully to open the space between the distal 
fibula, tibia, and calcaneus bones. Palpate this 
space and insert the needle from a caudolateral 
position. The needle should be advanced parallel 
to the calcaneus distally and slightly medially.
Elbow
• The elbow is flexed moderately to an 
approximately 45 degree angle. This opens 
the space between the humerus and the ulna.
• The joint is entered from the caudolateral 
aspect.
• Insert the needle between the olecranon 
process and the lateral condyle of the humerus 
and advance it distally and slightly medially, 
following the cranial surface of the ulna.
Scapulohumeral Joint
• Flex the joint slightly to widen the space. 
Palpate the greater tubercle and the acromion 
process of the scapula.
• Approach the joint from the lateral aspect 
and insert the needle slightly cranial and 
distal to the acromion process and just caudal 
to the greater tubercle. The needle should be 
directed in a caudal ­medial and slightly 
downward direction.• The joint space can be approached also 
from a cranial direction. Insert the needle 
medial to the greater tubercle and ventral to 
the supraglenoid tubercle, angling it in a 
cranial ­caudal direction.
• Joint fluid should be evaluated grossly for 
color, turbidity, viscosity, quantity, and ability 
to clot. A change in the color or viscosity of 
the joint fluid can indicate disease or blood 
• If the sample is contaminated with blood 
by a traumatic tap, the blood usually does not 
mix evenly, whereas blood from ongoing 
hemorrhage into the joint appears evenly 
distributed.
• Viscosity is assessed by expelling one to two 
drops of fluid from the syringe onto a slide. If 
the fluid is easily expelled, the viscosity is low. 
Formation of a string of fluid as it leaves the 
needle is consistent with normal viscosity.
• Many taps yield only a few drops of fluid, 
and complete fluid analysis may be difficult. 
Slides should always be submitted for cytologic 
evaluation because determining the type of 
cells in the fluid is the most helpful piece of 
information in defining the disease process.
• If enough fluid can be obtained, a small 
amount of the sample should be placed in an 
EDTA tube for fluid analysis.
• Culture and microbial sensitivity testing 
should performed. The probability of 
bacterial infection is greater in patients that 
have monoarthropathies and purulent ­
appearing joint fluid.
• Standard for sedation protocol
• Monitor for increased joint pain or swelling.
Figure 2.
Schematic representation of landmarks for the stifle joint.
Figure 3.
Schematic representation of landmarks for the tarsal 
joint.Arthrocentesis With Synovial Fluid Analysis  (continued)

Canine and Feline, Seventh Edition  1481
None
• In some cases, weight reduction is 
• Specific diets are available for dogs with 
Dependent on primary disease process.
• Dependent on primary disease process.• Allow patient to dictate activity level.
Anticipated Recovery Time
Immediate after recovery from sedation.
See Table 1.CRITICAL VALUES
None
None
• Severe skin disease or infection.(continued)  Arthrocentesis With Synovial Fluid Analysis
Figure 4.
Schematic representation of landmarks for the elbow joint.
Figure 5.
Schematic representation of landmarks for the shoulder joint.

1482  Blackwell’s Five-Minute Veterinary Consult  
T raumatic tap with blood contamination.
Species
• Feline chronic progressive polyarthropathy 
has been documented in male cats.
• Bacterial L ­form infection can cause a 
severe, erosive polyarthritis in cats.
• Calicivirus (both by natural infection and 
by vaccination) can cause a transient poly  ­ 
arthritis in young kittens.
Breed
• Arthrocentesis may be more difficult to 
perform in small ­breed dogs.
• An erosive polyarthropathy has been 
documented in young greyhounds.
• Swollen hock syndrome occurs in shar ­peis.
Age
None
Gender
None
Pregnancy
None
CLINICAL PERSPECTIVE
• An accurate medical history noting trauma and 
travel history and drug and toxin (e.g., NSAID, 
anticoagulant) exposure should be taken.
• Physical examination should include a 
thorough musculoskeletal and neurologic 
examination to differentiate joint disease from 
primary orthopedic or neurologic problems. 
Although careful attention must be paid to 
evaluating joints for effusion and pain with 
flexion or extension, it is extremely important to 
note that significant joint disease can be present 
despite a lack of abnormalities on joint palpation.
• Initial diagnostic testing that should be 
considered before joint taps are performed 
include a CBC, serum biochemistry analysis, 
urinalysis with a urine culture, and radiographs 
of affected and corresponding nonaffected joints. Vector ­borne disease testing should be 
performed. A coagulation panel can be 
submitted if hemarthrosis secondary to toxicity 
or inherited disease is suspected. Further studies, 
such as additional serologic testing for infectious 
disease and systemic testing for immune ­
mediated disease, should be considered when 
appropriate historical or clinical signs are 
present. Blood cultures may also be performed 
to look for a systemic infectious cause of joint 
• Occasionally (especially in cats), fever and 
lethargy are the sole presenting signs in 
animals with polyarthritis.
• It may be difficult to obtain good samples 
from cats and small dogs.
• Cell counts in normal synovial fluid are low 
and predominantly contain lymphocytes and 
mononuclear cells; increased neutrophil 
count is indicative of disease.
• Once an inflammatory process is defined, 
there is considerable overlap in cytologic findings 
between the specific causes of inflammation:
◦ In general, inflammatory disease is 
characterized by increased numbers of 
neutrophils and a variable increase in large, 
mononuclear cells in the joint fluid. Septic 
joints tend to have very high numbers of 
neutrophils, which may also exhibit 
degenerative changes. Bacterial organisms 
are usually not seen; Ehrlichia  sp. morulae 
are seen infrequently. Increased numbers of 
nondegenerate neutrophils are generally 
seen with an immune ­mediated process. A 
more complete review of cytologic changes 
in joint disease can be found in the 
Suggested Reading section.
• Rheumatoid arthritis, an erosive disease of 
the distal joints in small dogs, is extremely 
rare. Radiographs are helpful in making this 
diagnosis. Rheumatoid factor analysis is not 
necessary in the majority of cases.
• Reactive polyarthritis may be seen secondary 
to systemic infectious disease, drugs, neoplasia, 
or any chronic inflammatory condition.• With proper technique, significant 
complications are very rare.
• Radiographs: affected and unaffected joint.
• Infectious disease testing (Lyme, Ehrlichia , 
heartworm, Leishmania , Toxoplasma ).
• Antinuclear antibody serology.
• Urine protein/creatinine ratio.
• Rheumatoid factor.
SYNONYMS
Joint tap.
SEE ALSO
• Arthritis, Septic.
• Polyarthritis, Erosive, Immune ­Mediated.
• Polyarthritis, Nonerosive, Immune ­
Baker R, Lumsden JH. Synovial fluid. In: 
Color Atlas of the Cytology of the Dog and 
Cat. St Louis, MO: CV Mosby, 2000, pp. 
209–221.
Crow SE, Walshaw SO. Manual of Clinical 
Procedures in the Dog and Cat. Philadelphia, 
PA: JB Lippincott, 1987, pp. 196–197.
fluid. Vet Clin North Am Small Anim Pract 
2003, 33:153–178.
Taylor SM. Joint disorders. In: Nelson RW, 
Couto CG, eds., Small Animal Internal 
Medicine. St. Louis, MO: CV Mosby, 
2003, pp. 1071–1092.
Author  Rebecca A.L. Walton
acknowledge the prior contribution of Karyn 
HarrellTable 1
Abnormal values.
Variable Normal Trauma/Hemarthrosis Degenerative Arthropathy Inflammatory Arthropathy
Appearance Clear-to-straw colored Clear-to-red Clear-to-yellow Yellow-to-bloody, hazy/cloudy
Protein <2.5 g/dL Variable <2.5 g/dL Often >2.5 g/dL
Viscosity High Decreased Normal/decreased Decreased
Nucleated cell count (cells/ μL) <3,000 Increased RBCs 1,000–10,000 5,000 to >100,000
Neutrophils <5% Relative to blood <10% >10–100%
Mononuclear cells >95% Relative to blood >90% 10–<90%
Comments Small volume of fluid Erythophagia Macrophages Wide variationArthrocentesis With Synovial Fluid Analysis  (continued)

Canine and Feline, Seventh Edition  1483
Bacterial Culture and Sensitivity
  BASICS
TYPE OF SPECIMEN
Blood
Fluid
Tissue
Urine
Feces
TEST EXPLANATION AND RELATED 
PHYSIOLOGY
Culture and sensitivity testing to aid in 
diagnosis of infectious disease is one of the 
most common tests in the diagnostic 
laboratory. Proper specimen selection and 
collection are crucial to proper diagnosis. In 
addition, it is important to distinguish 
normal flora from infectious agents. When 
possible, samples for bacterial culture should 
be collected prior to the initiation of 
antimicrobial therapy as systemic antibiotic 
administration can impair microbial growth 
in vitro .
Different methodologies may be used to 
determine antimicrobial susceptibility. 
Kirby-Bauer disc diffusion and serial anti- 
biotic dilution to determine minimum 
inhibitory concentrations (MICs) are two of 
these methods. In addition to susceptibility 
data, it is important to understand the 
physiology of the location of infection as this 
can also affect antimicrobial selection.
To identify bacteria causing infection and 
determine the most appropriate therapy
None
None
None
Dependent on location of infection.
  SAMPLE
SAMPLE COLLECTION
The sample depends on the site of potential 
• Swab the site (e.g., ear, discharge) by using 
a sterile swab. Swabs tipped with inert, 
nontoxic rayon are preferred.
• Fine-needle aspirate—aseptic preparation 
of the aspiration site is important to 
prevent contamination of sample with 
normal skin flora.
• 0.5–1.0 mL of urine—cystocentesis is the 
method of choice. Aseptic catheterization can also be used, although quantitiative urine 
culture is preferred for these samples. Voided 
urine is not preferred due to potential 
contamination from the external urinary 
tract, and results must be interpreted in the 
context of quantitative data.
• 0.5–1.0 mL of effusion.
• Material aspirated from a lesion (e.g., 
abscess).
• Venous blood—sample size determined by 
manufacturer of the culture bottle and patient 
size, but larger sample volumes are preferred.
• Feces.
• Tissue biopsy.
• Wash fluid (tracheal wash, nasal flush, 
prostatic wash).
Aseptically prepare the skin prior to any 
percutaneous aspiration. Wounds should be 
cleaned and lavaged prior to collection of 
culture sample. For skin lesions, remove 
surface exudate by wiping with sterile saline 
or 70% alcohol prior to sample collection.
Aerobic Culture
• Sterile swab—swabs should be placed into 
some type of microorganism collection and 
transport container (e.g., BactiSwab, Remel, 
Lenexa, KS; BBL CultureSwab, Becton-
Dickinson, Franklin Lakes, NJ). These 
containers typically consist of a round-
bottomed sleeve designed to protect the 
sample. Some transport systems contain 
medium designed to enhance survival of any 
microorganisms present. When using a 
transport container with media, ensure that 
swab is completely immersed in culture 
medium.
• Submit fluids (urine, effusion, aspirated 
material, wash solutions) in a sterile tube with 
or without media. Plain red-top tubes are 
acceptable, but the use of serum separator 
tubes or plastic red-top tubes with clot 
activator should be avoided.
• Biopsy—place sample in a sterile container 
and add several drops of sterile 0.9% saline to 
keep tissue moist.
• Catheter tip—5 cm of the distal tip is 
sterilly cut and placed into a sterile container 
for transport.
Anaerobic Culture
• Tissue or aspirates of deep material are 
always superior to superficial swab specimens.
• If a swab must be used, pass it deep into the 
base of the lesion.
• Biopsy—place the sample in sterile 
container and add several drops of sterile 
saline to keep the tissue moist.
• If sample processing will be delayed >2 
hours, place sample into a specific anaerobic 
transport tube or vial. Anaerobic transport 
medium is a mineral salt-base soft agar with 
reducing agents designed to maintain an anaerobic environment for an extended 
period, maintaining viability of more 
fastidious microorganisms.
• Swabs of material are plunged deep into the 
agar so that even though material at the top 
of the tube is exposed to oxygen, material at 
the bottom of the tube remains anaerobic.
• T ransport fluids in an anaerobic transport 
vial. After cleaning the rubber stopper with 
alcohol, push the needle through the septum 
and inject the fluid on top of the anaerobic 
transport medium.
• Samples in anaerobic transport medium can 
generally be used for both aerobic and 
anaerobic cultures.
Fecal Culture
Use fecal transport medium when submitting 
for culture of Salmonella , Shigella , 
Campylobacter , and other fecal pathogens.
Mycoplasma Culture
Semen or mucus from respiratory tract can be 
submitted in a sterile container. Material can 
also be collected on a sterile swab and 
submitted in a microorganism transport 
container that contains Amies transport 
medium without charcoal, although this is 
not an optimal method.
Blood Culture
• Aseptically prepare venipuncture site.
• Remove the plastic cap covering each of 2 
blood culture bottles and decontaminate each 
rubber stopper with 70% alcohol. It is best to 
have both aerobic and anaerobic types of 
vials, however, venting anaerobic vials to 
make them aerobic can be done.
• Collect blood using sterile needle and 
syringe. A minimum of 4 mL of blood (2 mL 
for each bottle) is necessary:
◦ Better results may be achieved with larger 
sample volumes.
◦ Sampling volume should be based on the 
manufacurer’s recommendation for the 
blood culture bottles being used, the 
number of samples to be collected, and 
patient size.
• Change the needle prior to introducing 
sample into each bottle and divide sample 
between the two blood culture bottles; mix well:
◦ Blood should be sampled at 2 or 3 time 
points, 30–60 minutes apart. Each 
collection should occur from a different 
location/vein if possible.
SAMPLE STORAGE
• To increase viability of organisms and 
prevent overgrowth, refrigerate samples for 
routine aerobic culture until shipped.
• Specimens for anaerobic culture, blood 
culture, and fecal culture should be main-
tained at room temperature:
◦ All samples should be submitted/plated 
for culture as soon as possible to maximize 
results.

1484  Blackwell’s Five-Minute Veterinary Consult  
SAMPLE STABILITY
Aerobes
Refrigerate for ≈2 days.
Anaerobes
• Stable in an anaerobic transport tube for 
1–2 days (depends on organism).
• Stable in a red- top tube or standard 
microorganism collection and transport 
system for ≤2 hours.
• Refrigeration decreases viability.
PROTOCOL
None
• No growth of bacteria in culture from 
sterile fluids/sites.
• Growth of normal flora only, but no 
pathogenic organisms from nonsterile 
• Growth of pathogenic organisms.
• Kirby-Bauer microbial susceptibility results 
for antimicrobials are reported as either 
susceptible or resistant.
• Some antimicrobial susceptibility results are 
reported with an MIC, which is the lowest 
concentration of antibiotic that inhibits the 
growth of a given strain of bacteria. When 
using MICs to select an appropriate anti -
microbial, three criteria are important:
1. The MIC on the clinical microbiology 
report.
2. The antimicrobial’s normal range used 
to establish susceptibility. This represents 
the concentration of antibiotic that is 
reasonably achievable.
3. The breakpoint of the antimicrobial—
the dilution where the bacteria begin to 
show resistance.
• The breakpoint and the normal range differ 
by drug and bacterial species. Therefore, 
comparing antimicrobial MICs is based on 
differences between the breakpoint and the 
normal range for each antimicrobial. The 
further the MIC is from the breakpoint in its 
normal range, the more susceptible that 
organism is to the antimicrobial.
None
Drugs That May Alter Results or 
Drugs That Interfere with T est 
Methodology
Systemic antibiotic administration can inhibit 
in vitro  microbial growth.Drugs That Alter Physiology
None
Disorders That May Alter Results
None
Collection Techniques or Handling That 
• Specimens that are 2 days old may lose viability.
• Inappropriate containers:
◦ EDTA is bacteriostatic.
◦ The clot activator in serum-separator 
tubes and plastic red-top tubes may affect 
results.
◦ Samples for anaerobic cultures have 
limited viability if not transported in 
specific anaerobic transport tubes.
Influence of Signalment
Species
None
Breed
None
Age
None
Gender
None
Pregnancy
None
LIMITATIONS OF TEST
• Mycobacterium  sp. and Nocardia  sp. are 
difficult to culture and must be specifically 
requested.
• MIC is just one of the criteria used to select 
an antimicrobial. Antimicrobial selection also 
depends on the location of infection, what 
dose and route of administration will achieve 
adequate concentrations at that site, and how 
long the infection needs to be treated.
Sensitivity, Specificity, and Positive 
and Negative Predictive Values
None
Valid If Run in a Human Lab?
Yes, although human laboratories may not be 
able to perform susceptibility testing for 
veterinary-only approved antimicrobials.
• In cultures from a mucosal surface (e.g., 
tracheal wash, nasal swab, vaginal discharge, urine 
collected by catheter or free catch), interpretation 
must consider the presence of normal flora:
◦ Large numbers of a single microorganism 
in almost pure culture suggests a pathogenic 
process.
◦ A mixture of ≥4 different organisms in 
light to moderate numbers suggests growth 
of normal flora.
◦ Light growth from a sample submitted in 
enrichment broth suggests normal flora (or 
suppression of growth by antimicrobial 
therapy).• Specific anaerobic transport containers are 
more expensive than routine microorganism 
collection and transport containers (and may 
not be provided gratis by diagnostic labora -
tories), but can be readily obtained from 
commercial distributors of microbiology 
supplies and improve the likelihood of 
documenting an anaerobic infection.
• Chances of documenting bacteremia are 
increased by submitting 2 sets of blood cultures 
collected from different venipuncture sites or 
from the same site 15–30 minutes apart.
Dependent on the site of infection.
SYNONYMS
• Aerobic culture.
• Anaerobic culture.
• Blood culture.
SEE ALSO
• MIC = minimum inhibitory concentration.
Becton Dickinson (BD) Diagnostic Systems, 
Product Center, http://www.bd.com/ds/
productCenter/CT-PortACul.asp. Examples 
of anaerobic transport tubes/vials.
Aucoin D. Target: The Antimicrobial 
Reference Guide to Effective T reatment, 
2nd ed. Port Huron, MI: North American 
Compendiums, 2002.
Jones RL. Laboratory diagnosis of bacterial 
Diseases of the Dog and Cat, 3rd ed. St. 
Louis, MO: Saunders Elsevier, 2006, pp. 
267–273.
Mena E, Thompson FS, Armfield AY, et al. 
Evaluation of Port-A-Cul transport system 
for protection of anaerobic bacteria. J Clin 
Microbiol 1978, 8:28–35.
Author  April E. Blong
acknowledge the prior contribution of Terri 
Wheeler and Joyce S. Knoll.Bacterial Culture and Sensitivity  (continued)

Canine and Feline, Seventh Edition  1485
Blood Gas Interpretation
  BASICS
Blood
• Used to evaluate the acid–base status of 
patients:
◦ Arterial samples may be used to evaluate 
the adequacy of oxygenation and ventilation.
◦ Venous blood samples are not adequate 
for evaluation of oxygenation but may 
provide information about ventilation as 
long as perfusion is adequate.
• Normal physiologic reactions within the 
body occur at a specific pH value.
• Major variables evaluated when assessing 
acid–base status include the pH, HCO3− 
concentration, P co2 (partial pressure of CO2), 
and base excess (or deficit). Abnormalities 
within acid–base status are typically classified 
as acidosis, alkalosis, or mixed disorders.
• Each disorder may be caused by metabolic 
and/or respiratory abnormalities:
◦ The term metabolic  implies a net gain or 
loss of HCO3−
◦ The term respiratory  implies a net gain or 
loss of CO2.
• Pco2 and pH are inversely proportional, 
whereas there is a direct relationship between 
HCO3− concentration and pH.
• To interpret acid–base balance:
◦ Evaluate pH first—determine whether it 
is too high (alkalosis), too low (acidosis), or 
normal.
◦ Alkalosis is classified as metabolic if due 
to elevated HCO3− concentration (>24 
mmol/L) and respiratory if associated with 
a decreased P co2 (<36 mmHg).
◦ Acidosis is classified as metabolic if associated 
with a decreased HCO3− concentration (<20 
mmol/L), and respiratory if associated with an 
increased P co2 (>40 mmHg).
◦ With mixed acid–base disorders, two 
problems may either exacerbate the disorder 
(e.g., concurrent respiratory and metabolic 
acidosis) or mask the problem, producing a 
normal pH if the two disorders have 
opposite effects (e.g., concurrent metabolic 
acidosis and respiratory alkalosis).
• Generally, an acid–base disturbance is 
accompanied by compensation by either the 
respiratory system or the kidneys. This 
compensation attempts to return the pH to 
an overall normal range, but it is important to 
note that full compensation never occurs:
◦ Respiratory compensatory efforts occur 
immediately, whereas metabolic 
compensation will not reach its full level for 
2–3 days because changes in renal handling of HCO3− require time. In severe metabolic 
alkalosis, respiratory compensatory attempts 
will be limited by the hypoxemia that 
accompanies hypoventilation.
• Hypoxemia is a partial pressure of oxygen 
(Pao2) <90 mmHg at sea level. Hypoxemia 
has five potential underlying pathologies:
◦ Low inspired oxygen concentration—
may occur at altitude or with anesthetic 
machine malfunction
◦ Ventilation–perfusion mismatch—
reflects an altered balance between 
ventilated and perfused lung regions.
◦ Pure shunt—caused by cardiac defects 
(e.g., tetralogy of Fallot)
◦ Diffusion impairment—includes diseases 
that thicken the alveolar–capillary membrane.
◦ Hypoventilation (i.e., a P co2 >50 mmHg).
• When assessing the oxygenation status of 
patients, it is prudent to consider not only the 
Pao2 value but also to calculate the alveolar–
arterial (A-a) gradient. The normal range is <15:
◦ A-a gradient is calculated by subtracting 
the measured Pao2 from the calculated ideal 
alveolar oxygen partial pressure (PA o2) by 
using this formula:
PAO2 =  [% inspired O2 × (atmospheric  
− water-vapor pressure)] 
− (PaCO2/0.8)
◦ For example, breathing room air at sea level, 
normal dogs with a Pao2 of 95 mmHg and a 
Pco2 of 40 mmHg, the PA o2 will be 
[0.21(760 − 47)] − (40/0.8) = 150 − 50 = 100. 
The measured Pao2 of 95 mmHg is subtracted 
from this value to get an A-a gradient of 5.
◦ This formula is particularly useful if a 
patient has marked hyper- or 
hypoventilation.
◦ For example, a dog with a Pao2 of 84 and 
a Pco2 of 22 is hyperventilating. However, 
calculation of the A-a gradient gives a value 
of 38.5, which is elevated, suggesting that 
increased respiratory rate is compensating 
for primary lung disease.
◦ Conversely, in a dog with Pao2 of 65 and 
a Pco2 of 59, the A-a gradient is 11.25, 
which is normal, which indicates that 
hypoventilation, and subsequent 
hypoxemia, is caused by some disorder 
other than primary lung disease.
◦ At increasing inspired-oxygen 
concentrations, the A-a gradient becomes 
less accurate. Thus, if the concentration of 
inspired oxygen is directly known, a ratio 
of the Pao2 to the fractional inspired 
oxygen concentration (Fio2) may be 
calculated. The normal value for the  
Pao2/Fio2 is 100:0.21 or 476. In people and 
dogs, acute lung injury is present at a ratio 
<300 and acute respiratory distress 
syndrome at a ratio <200.INDICATIONS
• Assessment of acid–base balance.
• Assessment of oxygenation (arterial samples 
only).
• Avoid arterial collection when patients have 
severe coagulopathy.
cellulitis or open infection at the collection 
site.
• Hematoma at the sampling site.
• Collection of a venous sample instead of 
intended arterial sample and subsequent 
inappropriate patient management decisions.
None
• Endocrine and metabolic.
• Renal and urologic.
  SAMPLE
• Venous or arterial blood.
• Typically, heparinized blood samples are 
analyzed. Self-filling syringes are 
commercially available and routinely used for 
arterial samples.
• Samples should be collected under 
anaerobic conditions for the most accurate 
Pco2 and HCO3− values.
• Samples should be processed immediately 
to prevent altered values.
• Samples exposed to room air will have an 
increased Pao2 and decreased P co2.
If immediate analysis is not possible, samples 
may be stored anaerobically on ice for 4 
hours.
For 4–6 hours if kept on ice.
PROTOCOL
None
• pH: 7.36–7.44.
• Pco2: 36–40 mmHg.
• HCO3−: 20–24 mEq/L (or mmol/L).
• Base excess: ±4.

1486  Blackwell’s Five-Minute Veterinary Consult  
• Po2: 90–100 mmHg (at sea level, breathing 
room air [21% oxygen]).
• Reference intervals may vary, depending 
on sea level, laboratory, and assay.
ABNORMAL FINDINGS
Values above or below the reference range.
• pH: <7.2 or >7.5.
• Pco2: <20 or >55 mmHg.
• Po2: <60 mmHg (arterial sample).
• HCO3−: <13 or >33 mmol/L.
• Base excess (or deficit): >12.
None
Drugs That Alter Physiology
Supplemental oxygen, bicarbonate infusions, 
carbonic anhydrase inhibitors.Disorders That May Alter Results
None
• Difficulty in arterial puncture may result in 
either a fully or partially deoxygenated 
(venous) sample.
• Prolonged storage at room temperature will 
affect results.
• Administration of excessive heparin will 
dilute the sample and may result in altered 
values.
• Exposure of the sample to room air for an 
extended period of time (>1 minute).
Species
Arterial blood–gas collection is very 
challenging in cats. Cats are thought to have a 
lower P co2 than other species.
Breed
Brachycephalic dogs may have a lower Pao2, 
but this may reflect the relative difficulty of 
restraining them for sampling.Age
Whereas in people, decreased Pao2 
accompanies aging, this has not been found 
to be true in one study in dogs. A-a gradient 
may increase slightly with age.
Gender
None
Pregnancy
Advanced pregnancy in humans may cause an 
altered respiratory pattern that produces 
respiratory alkalosis with a compensatory 
metabolic acidosis. Pao2 is unchanged. This 
effect might be observed in late pregnancy in 
N/A
Yes.
CAUSES OF ABNORMAL FINDINGS
Table 1
Causes of abnormal findings.
Analyte High Values Low Values
HCO3−Metabolic alkalosis Metabolic acidosis
High GI obstruction Poor perfusion (lactic acidosis)
Profound hypokalemia
IatrogenicRenal failure
Diabetic ketoacidosis
Ethylene glycol intoxication
Compensation for respiratory acidosis Compensation for respiratory alkalosis
Pco2Respiratory acidosis
Severe respiratory failureRespiratory alkalosis
Panting
Fever
Cervical lesion
Opioid overdose
Large dog placed in lateral recumbencyPain
Compensation for metabolic alkalosis Compensation for metabolic acidosis
Po2Not significant Hypoxemia
Pulmonary disease
Edema
Contusions
Pneumonia
Pleural space disease
Pleural effusion
Diaphragmatic hernia
Cardiovascular shunts (e.g., tetralogy of Fallot)
Hypoventilation
Pain
Respiratory depressants
Intracranial disease
Cervical diseaseBlood Gas Interpretation  (continued)

Canine and Feline, Seventh Edition  1487
• Determine whether appropriate 
compensation is occurring or if two disorders 
are present. Guidelines for compensation are 
the following:
◦ Metabolic acidosis—each 1 mEq/L 
decrease in HCO3 will decrease P co2 by 0.7 
mmHg.
◦ Metabolic alkalosis—each 1 mEq/L 
increase in HCO3 will increase P co2 by 0.7 
mmHg.
◦ Respiratory acidosis.
▪ Acute—each 1 mmHg increase in P co2 
will increase HCO3 by 0.15 mEq/L.
▪ Chronic—each 1 mmHg increase in 
Pco2 will increase HCO3 by 0.35 mEq/L.
• Respiratory alkalosis:
▪ Acute—each 1 mmHg decrease in P co2 
will decrease HCO3 by 0.25 mEq/L.
▪ Chronic—each 1 mmHg decrease in 
Pco2 will decrease HCO3 by 0.55 mEq/L.
• Severe acidosis is common with ethylene 
glycol intoxication.
• All assessments of oxygenation should 
include assessment of the P co2 and, if 
warranted, calculation of the A-a gradient or 
Pao2/Fio2.
• It is crucial to recognize that an arterial 
blood gas merely provides objective evidence as to degree of impairment, but it is not 
specific for the cause.
• Serum biochemistry profile and urinalysis.
• Ethylene glycol test.
• Thoracic radiographs to look for 
cardiopulmonary disease.
• Echocardiography if heart may be affected.
SYNONYMS
• Oxygen (O2) saturation.
• Partial pressure of carbon dioxide in blood 
(Pco2).
• Partial pressure of oxygen in blood (P o2).
• pH.
SEE ALSO
• A-a gradient = alveolar–arterial gradient.
• Fio2 = fraction of inspired oxygen.
• HCO3− = bicarbonate.• Paco2 = arterial partial pressure of carbon 
dioxide.
• Pao2 = arterial partial pressure of oxygen.
• PAo2 = alveolar partial pressure of oxygen.
• Charlie’s Clinical Calculators, MedCalc: 
acid–base calculator: http://www.medcalc. 
com/acidbase.html
• Colorado State University, College of 
Veterinary Medicine & Biomedical Sciences, 
Veterinary Emergency and Critical Care 
Medicine: Acid/base, blood gas interpretation 
[at high altitude]: http://www.cvmbs. 
colostate.edu/clinsci/wing/fluids/bloodgas. 
htm
King LG, Anderson JG, Rhodes WH, 
Hendricks JC. Arterial blood gas tensions in 
healthy aged dogs. Am J Vet Res 1992, 
53:1744–1748.
Proulx J. Respiratory monitoring: arterial 
blood gas analysis, pulse oximetry, and 
end-tidal carbon dioxide analysis. Clin Tech 
Small Anim Pract 1999, 14:227–230.
Consulting Editor  Benjamin M. Brainard(continued)  Blood Gas Interpretation

1488  Blackwell’s Five-Minute Veterinary Consult  
Blood Pressure Determination: Noninvasive and Invasive
  BASICS
Blood pressure measurement.
• Blood pressure (BP) is the product of 
cardiac output and systemic vascular 
resistance. BP is indirectly related to organ 
perfusion, and the maintenance of normal BP 
is vital to maintaining organ function.
• Elevated (hypertension) and decreased 
(hypotension) BP can be seen in small animal 
patients:
◦ Hypertension most commonly occurs 
secondary to concurrent diseases (e.g., renal 
disease, hyperthyroidism, hyperadreno­
corticism, hyperaldosteronism, diabetes 
mellitus, obesity, and pheochromocytoma). 
Older cats may be hypertensive without a 
clear cause.
◦ Hypotension can occur as a result of 
shock (e.g., anaphylaxis, hypovolemia, 
sepsis, cardiac failure), as well as with the 
administration of certain medications (e.g., 
anesthetics, arterial vasodilators).
• Indirect BP is measured using two main 
methodologies: Doppler ultrasonic flow 
probe and oscillometric:
◦ Doppler can be used in cats and dogs, and 
readings can be obtained over a wide range of 
pressures, with variable heart rates. The 
Doppler measurement is likely between the 
systolic and mean arterial blood pressures, and 
should be interpreted as the systolic blood 
pressure to avoid misdiagnosis of hypotension.
◦ Oscillometric devices record mean 
arterial BP and calculate diastolic and 
systolic blood pressure as well. They are less 
accurate in patients with extreme brady ­ or 
tachycardias, and may be difficult to use in 
small patients. They are easy to use and 
lend themselves well to screening exams.
• BP can be measured directly (also called 
invasively) by introducing a catheter into an 
artery and then connecting this catheter to an 
external pressure transducer. Direct BP 
measurement requires expertise for arterial 
catheter placement, as well as for obtaining 
reliable readings, and is generally not suited 
for routine use in awake patients.
• When signs of end ­organ damage from 
hyper or hypotension are present, such as 
retinal hemorrhage and/or detachment, cardiac 
hypertrophy, or neurologic abnormalities.
• Part of full workup in patients with diseases 
known to cause hypertension.
• In patients with emergent clinical signs or 
those requiring critical care.
• Anesthetized patients.
• Patients receiving medications known to 
affect BP .CONTRAINDICATIONS
• Indirect BP—none.
• Direct BP—patients who cannot be sedated 
or anesthetized, lack of appropriate skill or 
equipment.
Indirect BP
None
Direct BP
• Hematoma formation at the puncture site.
• Pain related to venipuncture (can use local 
anesthetic block or place under sedation/
anesthesia).
• Thrombosis and potentially distal necrosis; 
feline metatarsal catheters should be removed 
within 6–8 hours of placement.
• Infection of the puncture site.
None
  PROCEDURE
None required for indirect measurement. With 
direct measurement, the site of arterial puncture 
should be clipped and sterilely prepared.
May affect measured BP . If direct BP readings are 
to be taken in a conscious patient, infiltration of 
local anesthetics can facilitate placement of the 
arterial line. Local anesthetic will also minimize 
arterial spasm in sedated or anesthetized patients.
• It is ideal to have the site where BP is being 
measured at the level of the heart.
• For oscillometric BP devices, the extremity 
with the cuff should not bear weight when 
the reading is taken.
None for indirect. With direct BP measure­
ment, the patency of the catheter needs to be 
maintained, and movement of the limb with 
the catheter should be minimized.
• Indirect BP measurement: oscillometric or 
Doppler device, cuff, and sphygmomanometer
• Direct BP measurement: pressure transducer, 
non­compliant tubing, multiparameter monitor
TECHNIQUE
Indirect
Doppler (Figure 1)
• Clip the area where BP is to be measured 
(the area just below the metacarpal or 
metatarsal pads, ventral aspect of tail).
• Apply ultrasound gel to the transducer.• Apply the cuff to the area above the 
transducer (the width of cuff should be 
30–40% of limb circumference) attached to 
the sphygmomanometer.
• Position the transducer so that a good 
arterial signal is heard.
• Inflate the cuff until the signal is no longer 
audible and then slowly deflate the cuff until the 
signal returns. The pressure at which the signal 
returns is considered to be systolic pressure.
• Repeat the measurement; wait at least 3–5 
minutes between readings.
Oscillometric
• Apply the cuff to appropriate site (between 
the elbow and the carpus, above the elbow, at 
the tail base, at the distal hind limb).
• Activate the machine to start automatic inflation 
and measurement. The heart rate reported by the 
machine should match the patient’s heart rate; if 
not, the measurement is incorrect.
• Repeat the measurement.
Direct
• Clip and surgically prepare the puncture 
site. Most common site is the dorsal pedal 
(metatarsal) artery; the tail artery can be used, 
and rarely the femoral artery.
• An over ­the­needle peripheral catheter (22 or 
20 gauge) is inserted into the area where the 
artery is palpated (femoral arterial catheters 
usually require a cut ­down procedure).
• Once blood has flashed into the catheter, 
the catheter is advanced into the artery and 
capped with an injection port or t ­set. The 
catheter is flushed with heparinized saline and 
taped or sutured in place.
• The t ­port is attached to noncompliant 
tubing that is filled with heparinized saline 
from a pressurized bag (pressure prevents 
blood from backing up into the arterial 
catheter). If a cap is left on the catheter, a 
needle attached to the noncompliant tubing 
may be used to pierce the injection port and 
the pressure may be monitored that way.
• The tubing is attached to a calibrated pressure 
transducer. The pressure transducer is then 
attached to appropriate monitoring equipment.
• If an automatic flush is not incorporated in 
the pressure monitoring setup, the tubing and 
catheter should be flushed with heparinized 
saline frequently to maintain patency.
N/A
• Indirect—none.
• Direct—following removal of the catheter, 
a tight bandage should be placed for 1–2 
hours, and after removal, monitor the arterial 
puncture site for indications of hemorrhage.
• Direct—apply a pressure bandage to the 
arterial puncture site upon removal of the

Canine and Feline, Seventh Edition  1489
cathter, and remove the bandage after 1–2 
hours to prevent pressure necrosis.
N/A
N/A
None
None
• Normal ranges depend on the method used 
to measure BP , age, breed, and, to some degree, 
operator factors (experienced vs. novice).
• An average value for BP in awake dogs is 
around 133/75 (systolic/diastolic) measured 
with an oscillometric monitor, giving a mean 
arterial pressure of 94 mmHg.
• In awake cats, normal BP has been found to be 
125/90 (mean of 101 mmHg) via direct methods.
Hypotension is considered to be present in 
most cases where mean arterial blood pressure 
is less than 70 mmHg.
• Critical hypotension is present with a mean 
arterial BP <60 mmHg or a systolic or 
Doppler pressure <80 mmHg.
• Critical hypertension is present with a 
systolic BP >180 mmHg and/or a diastolic 
BP >120 mmHg.INTERFERING FACTORS
• Most anesthetics will alter BP . Generally, 
pressure is decreased (e.g., propofol, 
isoflurane, sevoflurane); however, α2­
adrenergic agonists can cause an increase by 
increasing systemic vascular resistance.
• Beta­blockers, nitroprusside, and calcium ­
channel blockers may decrease BP .
• Ocular medications may affect BP; timolol can 
decrease BP and phenylephrine can increase it.
• Adrenergic agents (epinephrine, 
norepinephrine, dopamine) will increase BP .
N/A
Indirect
• Anything that leads to patient stress can 
lead to white ­coat hypertension and thereby 
inaccurate BP readings.
• The width of the cuff should be 30–40% of 
limb circumference. Cuffs that are too large 
may give falsely low readings, whereas cuffs 
that are too small can cause falsely elevated 
readings.
Direct
• Blood clots or air bubbles in the tubing 
may cause inaccurate readings for direct BP .
• Inappropriate tubing (using regular tubing vs. 
noncompliant) can fail to transmit the pressure 
wave appropriately, damping the signal.
• Excessively long tubing or kinking of 
tubing will cause erroneous readings.Influence of Signalment on Performing 
Species
Cat and dog normal ranges are similar.
Breed
No breed ­related differences have been noted 
in cats. Among dogs, sighthounds tend to 
have higher BPs than other breeds.
Age
BP increases with age.
Gender
Males will have higher BPs than females; on 
average, the difference is <10 mmHg.
Pregnancy
Unknown
• There are many indications for BP 
measurement, to detect both hypotension and 
• All anesthetized animals should have serial 
blood pressure measurements.
• In older animals, BP screening is indicated 
at regular visits.
• For general practice, indirect methods are 
best suited for screening patients.
• Direct BP measurement is ideal where 
continuous BP measurement is needed, 
especially in critical cases.
If hypertension is found, appropriate 
laboratory tests are indicated to identify 
whether an underlying cause exists.
SYNONYMS
None
SEE ALSO
Acierno MJ, Labato MA. Hypertension in 
dogs and cats. Compend Contin Educ Pract 
Vet 2004, 26:336–345.
Carr AP . Measuring blood pressure in dogs 
and cats. Vet Med 2001, 96:135–144.
Love L, Harvey R. Arterial blood pressure 
measurement: physiology, tools and 
techniques. Compend Contin Educ Pract 
Vet 2006, 28:450–461.
Waddell LS. Direct blood pressure monitor­
ing. Clin Tech Small Anim Pract 2000, 
15:111–118.
Author  Benjamin M. Brainard
Anthony P . Carr.
Figure 1 .
Doppler technique: blood pressure is being measured just below the metatarsal pad. Source: Lawrence P . Tilley(continued)  Blood Pressure Determination: Noninvasive and Invasive

1490  Blackwell’s Five-Minute Veterinary Consult  
Blood Sample Collection
  BASICS
Diagnostic sample collection
The procedure involves using a syringe with 
attached hypodermic needle to aspirate blood 
percutaneously through a vessel wall into the 
syringe to a desired amount. For arterial 
blood collection, a heparinized syringe with 
an attached needle is used. Blood samples 
may also be obtained through newly placed 
peripheral catheters, or central venous 
catheters.
To obtain a blood sample for test analysis.
• Severe coagulopathy (nonperipheral 
vessels).
• If a patient struggles or stresses to the point 
where it can further injure itself or the 
restrainers.
• Complications are rare.
• Excessive bleeding can cause a hematoma in 
patients with a coagulopathy. A pressure wrap 
over the venipuncture area can prevent of 
minimize this problem.
• Multiple venipunctures of the same vein 
and area could cause bruising, phlebitis, or 
thrombosis of the vein.
Clients should be warned that there might be 
an area of hair clipped at the site and a small 
bandage applied, which should remain in 
place for 1 hour after the procedure. Mild 
bruising or irritation of the skin may be 
present.
All
  PROCEDURE
• None.
• For arterial blood collection, oxygen 
therapy should be discontinued for 10 
minutes before sample collection if assessment 
of a patient breathing room air is desired.
• Generally no sedatives are required.
• If a patient is fractious, a mild sedative may 
be needed.Patient Positioning
• Proper positioning for the procedure is vital 
for a positive outcome.
• For venous blood collection, the patient will 
need to be restrained as needed for the vein 
being accessed and the vein compressed proximal 
to the planned site of puncture. For jugular 
venipuncture, it is best to have the patient in a 
sitting position with the head held high and 
slightly turned to the opposite side. For 
saphenous venipuncture, the vein is best viewed 
with the patient in lateral recumbency. Cephalic 
veins are best accessed when the patient is in 
sternal recumbency with the leg extended.
• For arterial blood collection, the patient 
will need to be restrained in lateral 
recumbency with the lower pelvic limb held 
out by the restrainer, being careful not to 
compress the artery and disrupt arterial blood 
flow. If a patient’s dyspnea worsens when in 
lateral recumbency, it may be necessary to 
perform this procedure with the patient 
standing or sitting.
• None.
• Dyspneic patients should be monitored 
closely for signs of increased dyspnea. If this 
occurs during the procedure, oxygen should 
be administered, and the patient allowed to 
sit calmly.
• An appropriately sized syringe, generally 
not larger than the amount of blood needed.
• A needle—use the smallest to cause the 
least trauma and pain to the patient but large 
enough to easily draw the volume of blood 
needed (e.g., 22 or 20 gauge × 1 inch). Larger 
needles are preferred if coagulation testing is 
planned.
• An alcohol swab.
• Appropriate collection tubes in which to 
place blood.
• A heparinized syringe for arterial blood 
collection (1- or 3-mL syringe with a 22 or 
25 gauge needle). Draw heparin into syringe 
and then push all of the heparin back into the 
heparin vial, leaving just enough to coat the 
inside of the syringe. Preheparinized, 
self-filling syringes are also available for 
arterial blood sampling.
• If drawing blood from a central venous 
catheter, a three-syringe technique should be 
used: a 3-mL syringe, filled with 0.5 mL of 
heparinized saline, is first filled to 3 mL as a 
“pre-sample.” Subsequently, the appropriate 
amount of blood for diagnostic sampling is 
obtained. The pre-sample is then reinfused 
back into the patient (the heparin in the 
saline prevents clotting), and the catheter is 
then flushed with heparinized saline to clear 
the catheter. Technically, the pre-sample 
should be 3–5 times the priming volume of 
the catheter lumen.TECHNIQUE
Prior to patient restraint, gather all supplies 
needed.
Venous Blood Collection
• Based on the amount of blood needed and 
the quality of the available veins, a vein will 
be selected by the venipuncturist. Typically, 
the jugular vein is used when more than 2 mL 
of blood is needed, and a coagulopathy is not 
present. An alternative to this is the lateral 
saphenous vein in dogs and the medial 
saphenous vein in dogs and cats, which works 
well if a patient is struggling. If a small 
amount of blood is needed (<2 mL), the 
cephalic vein may be used.
• The patient should be restrained, preferably 
on an examination table. The site is swabbed 
with alcohol. The vein is compressed proximal 
to the site to allow the vein to engorge. The 
needle is advanced through the skin and then 
into the vein lumen, and the syringe plunger 
pulled back to aspirate the appropriate amount 
of blood. Compression of the vein is released. 
The syringe and needle are then withdrawn as 
a unit and blood placed into appropriate 
collection tubes. The restrainer applies pressure 
directly to the venipuncture site for 15–20 
seconds then checks the site; if there is still 
bleeding, a bandage can be applied.
Arterial Blood Collection
• If a self-filling arterial blood syringe is used, 
pull the plunger back to the desired amount 
of blood needed (0.4 mL is adequate for most 
blood gas analyzers). The patient should be 
restrained with its bottom leg held out. The 
restrainer should put a hand behind the 
patient’s hock to keep its leg extended 
without compressing the artery.
• Preferred site is the pedal (metatarsal) 
artery, which courses over the metatarsal 
bones and courses into the hock joint. The 
tail, femoral, and lingual arteries have also 
been used to collect samples under varying 
conditions:
◦ The artery is identified by palpation with 
a finger of the nondominant hand (which 
may also hold the paw to keep the leg 
extended). The needle is then directed into 
the artery directly below the palpated pulse. 
The artery will generally exhibit some 
fremitis when the needle is near.
◦ If using a regular syringe, once the needle 
has penetrated the skin, negative pressure is 
created with the plunger of the syringe and 
the needle is directed to puncture the arterial 
wall. A flash of blood back into the syringe 
will usually be seen after arterial puncture. 
Allow the syringe to fill to the amount of 
blood needed, withdraw the syringe and 
needle, and have the restrainer place pressure 
over the site for several minutes. A small 
pressure wrap may be needed.

Canine and Feline, Seventh Edition  1491
◦ If using a self-filling syringe, once the 
artery is punctured, arterial blood 
pressure will fill the syringe until the 
porous filter of the plunger is reached, at 
which point the syringe contains an 
anaerobic blood sample.
◦ For both syringes, following sample 
acquisition, the syringe contents should be 
protected from room air. The needle may 
be placed into a rubber stopper or eraser, or 
the needle removed and the syringe capped 
with a specialized stopper (usually provided 
with the self-filling syringes).
◦ Due to proximity of the nerve to the 
artery, arterial puncture may be associated 
with pain, and the animal may pull the leg 
back during the procedure.
• Venous samples should be placed into 
appropriate collection tubes immediately to 
prevent clot formation. The tubes containing 
anticoagulant should be filled before the clot 
tubes. Invert the tubes at least 5 times to mix 
the samples thoroughly with the anticoagulant.
• Arterial samples for blood gas analysis 
should be assayed immediately.
Remove the pressure wrap 1 hour after the 
procedure and verify lack of continued 
bleeding or hematoma.
NoneDietary Modification
None
None
None
Immediate recovery is expected.
None
None
See Blood Gas Interpretation.
None
NoneInfluence of Signalment on Performing 
Species
Vein selection may vary between dogs and 
cats.
Breed
None
Age
None
Gender
None
Pregnancy
None
When performed skillfully by trained, 
experienced personnel, venipuncture for 
blood sampling is usually a quick, simple 
procedure that causes minimal discomfort to 
patients and can be a valuable diagnostic tool.
Blood gas analysis.
SYNONYMS
Venipuncture
Author  Robin Lazaro
Consulting Editor  Benjamin M. Brainard(continued)  Blood Sample Collection

1492  Blackwell’s Five-Minute Veterinary Consult  
Blood Smear Microscopic Examination
  BASICS
Blood smear (see Blood Smear Preparation).
• Cell counts derived from an automatized 
hematology analyzer must be correlated to 
findings in a manual examination of a 
peripheral blood smear:
◦ Confirm cell counts.
◦ Identify unusual cell types (including 
neoplastic cells).
◦ Identify morphological changes such as 
toxic change or left shifts, reactive 
lymphocytes, polychromatic cells, nucleated 
erythrocytes (nRBC), and immature 
◦ Identify parasites.
• With every complete blood count (CBC).
• To confirm results from an automated 
hematology analyzer.
• To characterize erythrocytes and classify 
anemia.
• To diagnose inflammation, hematopoietic 
neoplasia, and bone marrow disease.
• To evaluate platelets, especially if auto-
mated counts are low.
• To identify circulating parasites.
None
None
12-hour fasting samples are preferred to 
prevent lipemia, which can interfere with 
RBC morphology evaluation.
Hematologic, lymphatic, and immune.
  SAMPLE
Previously prepared blood smear (see Blood 
Smear Preparation).
• Slides should not be exposed to formalin or 
formalin fumes.
• Slides should be protected from breakage.
• Do not scratch or refrigerate slides.
• If slides do not have a coverslip, oil should 
be gently blotted away rather than wiped.
Store slides in shatterproof containers at room 
temperature.SAMPLE STABILITY
• Air-dried slides can be stored at room 
temperature indefinitely. They are stable 
months to years if fixed, stained, and not 
exposed to dust, light, or heat.
• For long-term storage, a permanent 
coverslip is recommended.
PROTOCOL
• Smears should be evaluated systematically:
◦ Gross examination of slide quality.
◦ Evaluate all cell lines at low-(10× 
objective), medium (40–50× objective), and 
high-power (100× oil objective) 
◦ Evaluate number and morphology of 
neutrophils, banded neutrophils (bands), 
lymphocytes, eosinophils, monocytes, and 
basophils.
◦ Unusual cells that can be seen include 
immature granulocytes, lymphoblasts, mast 
cells, and nRBC.
◦ A nucleated cell differential should be 
performed, platelet numbers and presence/
absence of clumping should be estimated, 
morphological changes of red blood cells 
(RBCs) and white blood cells (WBCs) 
should be noted, and presence of parasites 
(e.g., microfilaria) or inclusions should be 
Macroscopic Evaluation
• Confirm patient identity (slide label).
• Evaluate the quality of the blood smear. If 
the quality is poor, make a new blood smear 
(see: Blood Smear Preparation):
◦ Smear should be shaped like a parabolic 
cone (similar to the flame of a candle) with 
a blunt base, almost parallel sides, and a 
gently curved feathered edge at the nose.
◦ Smear should cover 1/3 to 2/3 of the 
slide, however the quality of the monolayer 
and feathered edge are more important than 
the overall surface area.
◦ The stain quality should be adequate for 
proper cell identification.
Low Power Evaluation
• At low power (10× objective), scan the 
entire smear.
• A monolayer where erythrocytes are closely 
opposed without overlapping should be 
present near a gently feathered edge (see 
Figure 1):
◦ With experience, a marked decrease or 
increase in RBC number can be detected.
◦ Anemic samples have a larger monolayer 
with increased space between cells 
extending into the smear base, while 
polycythemic samples have a minimal to 
absent monolayer.
◦ Perform a reticulocyte count if anemia is 
• Identify potential RBC agglutination and 
differentiate from rouleaux. If agglutination is 
suspected, perform a saline agglutination test.• At the feathered edge, search for microfi-
laria and large unusual cells (e.g., mast cells, 
lymphoblasts, other leukemic cells).
• Identify and evaluate the severity of platelet 
and leukocyte clumping at the feathered edge 
or base.
• WBCs are unevenly distributed in a smear; 
heavier and larger cells are more abundant at 
the base and feathered edges. Lymphocytes 
are more abundant than neutrophils in the 
thinner parts of the center and monolayer. 
Evaluate all areas of the slide for a more 
representative assessment.
• In the main body of the smear, estimate 
overall WBC count with a 10× objective. 
Average cells/field × 100 = approximate 
cells/ μL:
◦ When counting WBCs, include at least 1 
field in the base and feathered edge when 
determining the average to compensate for 
uneven leukocyte distribution. Moving 
from feathered tip to base is helpful.
Medium Power Evaluation
• If the slide is coverslipped, evaluate with a 
40× objective. If the slide is not, use a 50× oil 
objective.
• Begin at the feathered edge to identify 
larger uncommon cells (mast cells, lympho-
blasts, etc.), then move to the monolayer to 
perform a leukocyte differential:
◦ Due to uneven distribution of leukocytes, 
systematically move from edge to edge, a 
zig-zag, or alternating squares/Greek key 
pattern (Figure 2) to perform the 
◦ Classify 100 nucleated cells as neutro-
phils, bands, lymphocytes, monocytes, 
eosinophils, basophils, or other/unclassifi-
able (blasts, immature granulocytes, mast 
cells, etc.). Count nRBCs separately (do not 
include in the differential):
▪ If there is a leukocytosis (>30,000 
cells/ μL) or >2% other cells, count 500 
cells. Multiply your total WBC count 
(estimated or automatized hematology 
analyzer results) by the differential to 
calculate absolute cell counts.
◦ If there is >2% nRBC, calculate a 
corrected WBC count. The formula is:
Corrected WBC = (Measured WBC × 
100)/(100 + # nRBC seen)
◦ Note morphological changes to 
leukocytes such as neutrophil toxic change, 
reactive lymphocytes, monocyte vacuolation, 
viral inclusions, and presence of parasites.
• Perform an initial evaluation of erythro -
cytes for polychromasia, anisocytosis, 
poikilocytes, parasites, and inclusions 
including Heinz bodies, Howell-Jolly 
bodies, basophilic stippling, and iron 
(siderotic) inclusions.

Canine and Feline, Seventh Edition  1493
• Note location (cytoplasmic, nuclear, 
epicellular) and type of cell affected by 
parasites and inclusions.
• Roughly evaluate number and size of 
platelets, looking for smaller clumps.
High Power Evaluation
• Evaluate both the monolayer and feathered 
edge with a 100× oil objective, focusing on 
cell morphology, parasites, and inclusions.
• Perform a close evaluation of erythrocytes 
for variation in cell size, color, inclusions, and 
shape abnormalities including spherocytes, 
echinocytes, keratocytes, schistocytes, 
acanthocytes, leptocytes, stomatocytes, and 
codocytes:◦ Quantify morphologic RBC changes 
using the following grading scheme:
▪ Rare = <1 per 100× objective fields
▪ Occasional = 1–3 per 100× objective 
field
▪ Few or mild = 4–10 per 100× objective 
field
▪ Moderate = 10–25 per 100× objective 
field
▪ Many or marked = >25 per 100× 
objective field
• Search again for erythroid parasites and 
inclusions; some are not visible below 100×.
• Perform a closer evaluation of morphologi-
cal changes to leukocytes (listed above).• Count platelets at 100× in the monolayer, 
in a minimum of 10 fields, and evaluate for 
abnormal morphology and microclumping. 
Average platelets per 100× oil field × 20,000 
= approximate platelets/ μL.
• Adjacent erythrocytes that barely touch or 
rarely overlap in the monolayer, 1–2 poly  - 
chromatic cells per 100× objective field, mild 
anisocytosis, few poikilocytes, and no 
inclusions.
Thick Area of Smear Monola yer
Specimen
Figure 1 .
This drawing of a blood smear illustrates how cell morphology 
is optimal in the monolayer just behind the feathered edge, 
where RBCs are evenly distributed. Cells in thicker areas, 
toward the back of the smear, are less flattened and appear 
smaller and darker and are more difficult to identify. The 
overlap of cells, in thicker portions of the smear, further 
obscures and distorts their morphologic features.
PATITENT
NAMEPATITENT
NAME
Figure 2.
Perform a leukocyte differential using a zig-zag or 
alternating squares/Greek key pattern.(continued)  Blood Smear Microscopic Examination

1494  Blackwell’s Five-Minute Veterinary Consult  
• Approximately 5–15 WBCs per 10× 
objective field, with 60–80% mature 
neutrophils and no morphologic 
• Approximately 10–25 platelets per 100× 
objective field in the monolayer without 
clumping.
• No parasites.
• Tightly packed or widely spaced RBCs.
• Absolute WBC or platelet numbers above 
or below the reference interval.
• Morphological abnormalities in any cell line.
• Parasites present.
• Less than 1–3 neutrophils per 10× objective 
field suggests marked neutropenia and 
increased risk of infection.
• Less than 1–3 platelets per 100× objective 
field, without clumps present, suggests 
thrombocytopenia severe enough to cause 
bleeding.
None
• Glucocorticoids can cause leukocytosis, 
neutrophilia, lymphopenia, and variable 
• Epinephrine can cause neutrophilia, lympho -
cytosis, and variable thrombocytosis.
• Heinz bodies (see Anemia, Heinz Body) are 
caused by oxidative damage from numerous 
drugs including acetaminophen, benzocaine, 
phenazopyridine, propofol, and vitamin K.
• Most chemotherapeutic agents can cause 
pancytopenia (see Pancytopenia), as can many 
other medications including chloramphenicol 
(feline), estrogen (canine), griseofulvin, 
methimazole (feline), phenobarbital, phenylb -
utazone (canine), and trimethoprim-sulfa.
• Chloramphenicol and phenylbutazone can 
cause neutrophilic vacuolation.
• Hemolysis causes a thick pink background 
that distorts cells.
• Lipemia can cause RBC smudging.
• Hyperglobulinemia causes a thick blue 
background that distorts RBCs and causes 
pseudo-agglutination.
• Poorly mixed blood can produce a thin 
smear, and misrepresent the WBC count and 
differential.• Clotted blood artificially decreases platelet, 
RBC, and WBC numbers.
• Samples collected in sodium citrate 
anticoagulant have decreased platelet counts 
than those with EDTA anticoagulation 
(multiply count by 1.1 to account for 
dilution from liquid citrate anticoagulant).
• Poor blood smear preparation prevents 
accurate evaluation (see Blood Smear 
Preparation).
• Aged blood has increased platelet clumps 
and altered cell morphology including nuclear 
pyknosis, nuclear hypersegmentation in 
neutrophils, and cytoplasmic vacuolation.
• Epicellular parasites can detach over time 
and may be missed if smears are not made 
immediately after collection.
• Old stain or poor washing produces stain 
precipitate that can be mistaken for bacteria 
or parasites.
Species
• Canine RBCs have a prominent zone of 
central pallor with little anisocytosis, while 
feline RBCs are smaller without obvious 
central pallor and more anisocytosis.
• Cat RBCs are more susceptible to Heinz 
bodies.
• Canine eosinophils (except in sighthounds, 
see below) have rounded granules while feline 
eosinophils have smaller granules shaped like 
rice grains—this can be used to differentiate 
mislabeled samples.
• Basophils have more indistinct granules in 
dogs and cats relative to other species.
Breed
• Higher RBC counts have been reported in 
German shepherd dogs, boxers, greyhounds, 
and dachshunds.
• Decreased RBC size (microcytosis) is 
reported in Akitas, chow chows, Chinese shar 
peis, and shiba inus.
• Akitas with high and low RBC potassium 
phenotypes have different erythrocyte 
parameter findings.
• Hereditary macrocytosis is reported in poodles.
• Congenital stomatocytosis is reported in 
Alaskan malamutes, Drentse partrijshonds, 
and miniature schnauzers.
• Lower WBC counts are reported in 
greyhounds, Belgian tervurens, and border 
collies.
• Gray eosinophils in sighthounds such as 
greyhounds, Italian greyhounds, and whippets 
can be difficult to detect and missed by 
automated analyzers.
• Marked lymphopenia is reported in basset 
hounds and Jack Russell terriers with severe 
combined immunodeficiency syndrome 
(SCID).• Increased eosinophils have been reported in 
Bernese mountain dogs, Brittanys, rottweil-
ers, and German shepherd dogs.
• Lower platelet counts are reported in 
sighthounds including North American 
Scottish deerhounds and greyhounds, and 
also in the Polish hound (ogar Polski).
• Lower platelet counts with large platelets 
(macrothrombocytopenia) is an autosomal 
recessive trait present in cavalier King Charles 
spaniels and Norfolk and Cairn terriers.
• Cyclic hematopoiesis in gray collies can 
cause various waxing and waning cytopenias.
Age
None
Sex
None
Pregnancy
None
LIMITATIONS OF THE TEST
Smear quality, smear staining properties, 
evaluator experience, and adequate micro-
scope are crucial to accurate evaluation and 
N/A
Valid if Run in a Human Lab?
Generally no, unless technicians have 
specialty training in morphological evaluation 
of cells from veterinary species.
Manual review of a blood smear can give 
insight beyond what may be obtained from 
automated machine analysis.
• RBC, WBC, and platelet counts from an 
automated hematology analyzer.
• Buffy coat smear evaluation.
• Bone marrow aspirate and core biopsy.
• Flow cytometry (or other 
immunophenotyping) for suspected 
lymphoid or myeloid leukemia.
SYNONYMS
• Peripheral blood smear evaluation.
• CBC review.
• CBC evaluation.
• CBC = complete blood count.
• EDTA = ethylenediaminetetraacetic acid.Blood Smear Microscopic Examination  (continued)

Canine and Feline, Seventh Edition  1495
• nRBC = nucleated red blood cell 
(metarubricyte).
• SCID = severe combined immunodeficiency.
• http://www.eclinpath.com/hematology/
hemogram-basics/blood-smear-examination/• https://todaysveterinarypractice.com/
in-clinic-hematology-the-blood-film-review/
• https://www.youtube.com/
watch?v=wIZtvTGJL6M
• https://prezi.com/35zh5w9nr-qj/
the-veterinary-technicians-guide-to-
performing-a-blood-film/Suggested Reading
Harvey JW. Hematology procedures. In: 
Veterinary Hematology: A Diagnostic 
Guide and Color Atlas. Philadelphia, PA: 
Saunders, 2011, pp. 11–32.
Author  Paula M. Krimer
Consulting Editor  Benjamin M. BrainardTable 1
Causes of common hematopoietic abnormalities.
High Values Low Values Abnormal Morphology
Neutrophils Infection
Corticosteroid response
Epinephrine responseSepsis/infection
Overwhelming inflammation
Immune-mediated disease
Drug toxicity
Bone marrow diseaseMarked inflammation or infection
Leukemia
Pelger–Huët anomaly
Lymphocytes Antigenic stimulation
Epinephrine response
Lymphoid neoplasia/
LeukemiaInflammation/stress
Acute infections
Lymphatic fluid lossVaccination
Infection
Leukemia
Eosinophils Parasitism
Allergic/hypersensitivity reaction
ParaneoplasticNot significant Pelger–Huët anomaly
Erythrocytes Dehydration
Splenic contraction
Hypoxia
Polycythemia veraHemorrhage, acute or chronic
Intravascular or extravascular hemolysis
Parasitism
Chronic disease
Renal disease
Bone marrow diseaseRegenerative anemia
Heavy metal and other toxicities
Myelodysplastic syndromes
Platelets Regenerative anemia
Iron deficiency
HypercortisolemiaImmune-mediated disease
Tickborne diseases
Consumption (e.g. disseminated 
intravascular coagulopathy)
Bone marrow diseaseRegeneration
Breed-specific(continued)  Blood Smear Microscopic Examination

1496  Blackwell’s Five-Minute Veterinary Consult  
Blood Smear Preparation
  BASICS
Diagnostic sample preparation
• Preparation of a good-quality air-dried 
blood smear is necessary for accurate 
• Smears should have a feathered edge and a 
monolayer with even cell distribution for a 
reliable WBC differential, visualization of cell 
appearance, and adequacy for parasite 
• Sample aging impacts leukocyte morphology 
and platelet couns, therefore immediate 
preparation of a good-quality blood smear is 
• Prepared slides should be submitted with 
the corresponding anticoagulated blood for 
all complete blood counts (CBCs) sent to a 
referral laboratory.
Every time an in-house CBC is performed, 
and when a CBC is sent to a referral 
laboratory.
Results are inaccurate if blood clots are 
present in the sample. A fresh blood sample 
should be taken if clots are present. Slides 
should be protected from exposure to 
None
  PROCEDURE
Preprocedure Medication or Preparation
• Sterilize the venipuncture site with alcohol. 
The site may be shaved if needed.
• Collect blood (see Blood Sample Collection) 
and transfer into an anticoagulant tube; 
EDTA (purple top) is preferred for most 
species but lithium heparin (green top) may 
provide better cell morphology for some 
birds, reptiles, and amphibians:
◦ Heparin is sometimes used in small 
animals with small blood volume in order to 
have sufficient plasma for biochemical tests.
◦ Sodium citrate anticoagulant can also be 
used but counts should be multiplied by 
1.1 to account for dilution.Anesthesia or Sedation
Not required but may be helpful for clean 
venipuncture in fractious animals.
Varies with preferred venipuncture site.
Observe venipuncture site for hemorrhage, 
bruising, or hematoma formation.
• New glass slides.
• Pencil for labeling slide.
• Microhematocrit tube or 22–25G needle.
• Stain (for in-clinic evaluation).
TECHNIQUE
• Label glass slide with patient name, using a 
pencil. Markers and pens wash off with some 
stains.
• Gently mix anticoagulated blood for even 
distribution of cellular constituents. A tube rocker 
can be used or the tube manually inverted 5 times.
• A small droplet of blood should be placed 
near the edge of a new glass slide. Droplets 
can be applied with a microhematocrit tube 
or needle.
◦ The most common error in slide 
preparation is too large a drop. Reduce the size 
of the drop and repeat if a good monolayer 
and feathered edge are not obtained.
• Use a second clean glass slide to spread the 
drop. Begin by placing the second slide at a 
30-45° angle to the first where the blood will 
be spread (see Figure 1).
• Back the spreader slide into the drop. Let 
the blood migrate along the contact edge and 
toward the periphery (~5 seconds).
• When the blood has spread close to the edges 
of the slide, gently float the top slide away from 
the drop towards the end of the lower slide 
without applying downward pressure.
• Air-dry rapidly by waving the slide in the 
air or placing under a table fan (do not blow 
on slides).
• Stain with a Romanovsky-type stain (e.g., 
Diff-Quick, Wright-Giemsa, etc.) if 
evaluating in-house. Slides sent to external 
laboratories should be unstained.
• Package in appropriate shatterproof containers 
for transportation to external laboratories.
exposed to dust, light or heat.
• Avoid exposure to any formalin, even 
formalin fumes from a nearby biopsy specimen.
Postprocedure Patient Monitoring
N/A
N/ADietary Modification
N/A
N/A
N/A
Anticipated recovery time
N/A
• See Blood Smear Microscopic Examination.
• A good smear is shaped like a parabolic 
cone (similar to the flame of a candle) with a 
blunt base, almost parallel sides, and a gently 
curved feathered edge at the nose.
present near a gently feathered edge.
• The smear should cover 1/3 to 2/3 of the 
slide; however a large smear is not the goal. 
The quality of the monolayer and feathered 
edge are more important than the overall 
surface area. If either are not present, make a 
new smear.
Causes of Abnormal Values
See Tables 1 and 2.
None
(a)
(b)
(c)
(d)
Figure 1 .
Proper technique for blood smear preparation.

Canine and Feline, Seventh Edition  1497
None
Marked polycythemia causes increased blood 
viscosity that can prevent smooth distribution of 
cells, preventing the formation of a monolayer 
and distorting leukocyte morphology. Lowering 
the spreader slide angle may help.
May Alter Results (see Tables 1 and 2)
• Blood aging prior to slide preparation will 
cause platelet clumping and altered leukocyte 
morphology including nuclear pyknosis, 
nuclear hypersegmentation in neutrophils, and 
cytoplasmic vacuolation. Slides should be 
made as soon as possible after blood collection.
• Poorly mixed samples can cause a thinner 
smear mimicking anemia and misrepresentation 
of the leukocyte differential.
• Clots in the blood sample will decrease the 
presence of platelets on the smear and may 
alter the leukocyte differential.
• An inadequate feathered edge will interfere with 
detection of platelet clumps and abnormal cells.
• Any exposure to formalin fumes fixes the 
slides, preventing adequate cytological staining. 
Erythrocytes will appear blue-green and leukocytes cannot be accurately identified. Slides 
exposed to formalin should not be evaluated.
Species
The choice of EDTA, lithium heparin, or 
sodium citrate as an anticoagulant varies by 
species for best cellular morphology balanced 
with the need for collection of plasma or 
minimizing blood collection volume. Research 
species prior to selecting an anticoagulant.
Breed
None
Age
None
Sex
None
Pregnancy
None
• Slide quality matters; it is easier to made 
smooth smears on better quality slides. Use new 
glass slides, preferably with a negative charge.
• Sample aging changes leukocyte morphology 
and platelet counts—make slides immediately.
• Fresh smears may be necessary to identify RBC 
parasites including hemotropic Mycoplasma  spp.
• Some erythroid parasites, such as Babesia  
sp., may be more readily identified in 
capillary blood such as from an ear prick.  MISCELLANEOUS
None
SYNONYMS
Peripheral blood smear.
SEE ALSO
• Blood Smear Microscopic.
• EDTA = ethylenediaminetetraacetic acid.
https://www.vet.cornell.edu/animal-health-
diagnostic-center/laboratories/clinical-
pathology/samples-and-submissions/
hematology#Bloodsmear but it goes to https://
www.vet.cornell.edu/animal-health-diagnostic-
center/laboratories/clinical-pathology
https://www.youtube.com/watch?v=nbRUiWl2Qrs
http://www.eclinpath.com/hematology/sample-  
collection-heme/
Common staining mistakes.
Problem Appearance Probable Causes Solution
Bacterial growth 
in stainScattered extracellular bacteria, sometimes 
on a different plane of focusStain used for nonsterile procedures 
(e.g., skin lesions).Use separate stain for cytology and 
hematology. Replace stain frequently
Poor coloration Pale colors or insufficient contrast Insufficient time in dye or fixative, 
wrong pH water rinse, evaporated 
solutionsStandardize time per dip using a stopwatch. 
Use pH buffered distilled water to rinse. 
Tightly cap stains
Stain precipitate Darkly basophilic dots, sometimes 
aggregated, on a different plane of 
focusAged staining solution, evaporated 
solutions, or inadequate rinsing of 
slidesFilter or replace stain. Tightly cap stain when 
not in use. Rinse with distilled rather than 
tap water
Water artifact Moth-eaten cells, refractile “inclusions” Too much water in fixative Replace fixative
Table 2
Common smear preparation mistakes.
Problem Probable Causes Solutions
Blunt end (not arced) Spreader slide lifted abruptly Lift spreader slide gently. Smaller drop may be needed
Blood reaches far edge Too large a drop, spreader slide too low or moved 
too slowlyUse smaller drop. Raise the angle of the spreader slide or spread 
faster
Mono layer absent  
(thick smear)Too large a drop, spreader slide too high, 
apolycythemiaUse smaller drop and/or lower the angle of the spreader slide
Striations (chatter) Spreader slide moved too slowly or inconsistently Move spreader slide faster and/or more gently. Reduce 
downward pressure
Abnormal shape Spreader slide corner lifted Move spreader slide more gently and smoothly
Rough feathered edge Unclean spreader slide, large platelet clumps Use a clean slide. Remix blood. Repeat with lower angle(continued)  Blood Smear Preparation

1498  Blackwell’s Five-Minute Veterinary Consult  
Blood Typing
  BASICS
Blood
• Blood types are genetic markers on the 
surface of red blood cells (RBCs):
◦ Species-specific and antigenic (immune 
system can recognize and potentially 
produce antibodies against them).
◦ A set of 2 or more alleles at 1 gene locus 
makes up a blood group system.
◦ An individual lacking a given blood type 
may develop antibodies against it, either 
naturally (e.g., AB system in cats) or following 
sensitization via a mismatched transfusion.
◦ In dogs and cats, blood-typing methods 
are mostly based on agglutination reaction 
in which a species-specific antiserum or a 
lectin is directed against specific RBC 
antigens.
• In dogs, an international standardization 
proposed seven blood groups, referred to as 
Dog Erythrocyte Antigen (DEA), followed by 
a number. Since then, two new canine blood 
groups have been recognized:
◦ The Dal blood group was discovered 
following blood incompatibility in a 
previously-transfused anemic Dalmatian. 
Dal-negative dogs are rare and at high risk 
of transfusion incompatibility if they are to 
receive multiple blood transfusions, 
considering the fact that all blood donors 
tested to date are Dal positive.
◦ T wo additional canine blood types, Kai 1 
and Kai 2 have recently been identified, but 
their clinical significance remains unknown.
• For each blood group, a dog may be either 
positive or negative, so an individual dog’s 
RBCs can have several of these blood groups 
on their membranes. Flow cytometry analysis 
of the DEA 1 antigen using a monoclonal 
antibody revealed that the expression of DEA 
1 is a continuum of reactions ranging from 
negative to strongly positive, i.e., that all the 
alleles of the DEA 1 system have a similar 
epitope. Consequently, the historical 
nomenclature DEA 1.1, 1.2, 1.3, and DEA 
1.1 negative is now simplified to DEA 1 
positive and DEA 1 negative.
• Dogs do not have clinically significant 
naturally occurring alloantibodies; however, 
they may become sensitized after receiving a 
blood type-mismatched transfusion. DEA 1 is 
the most antigenic blood group in dogs. For 
this reason, blood typing for DEA 1 is 
desirable prior to transfusions to avoid 
• In cats, the AB blood group system is the 
predominant system, consisting of three blood types: A, B, and AB. The a allele is 
dominant over the b allele. The rare ab allele, 
causing the blood type AB, is separately 
inherited, being (co)-dominant to b and 
recessive to the a allele:
◦ Although most cats are type A in North 
America (>95% of domestic shorthairs), 
significant geographic and breed-associated 
differences exist in the frequencies of these 
blood types.
◦ Cats possess naturally occurring 
alloantibodies against the blood type they 
are lacking.
▪ Type B cats have very strong anti-A 
alloantibodies, such that transfusion of 
type A blood into a type B cat will 
produce a life-threatening acute 
transfusion reaction.
▪ Approximately 1/3 of type A cats have 
detectable weak anti-B alloantibodies, 
which may cause shortened survival of 
transfused B cells in type A cats.
◦ In 2007, a blood type called Mik was  
identified outside of the feline AB blood 
group and found to be capable of causing a 
hemolytic transfusion reaction. Unfortunately, 
blood typing for Mik is no longer possible.
• Easy-to-use blood-typing kits are commer-
cially available for in-practice determination 
of canine DEA 1, and feline A, B or AB 
◦ The RapidVet-H canine and feline 
blood-typing cards (DMS Laboratories, 
Flemington, NJ) provide results in approx -
imately 2 minutes. The animal blood type is 
indicated by visible RBC agglutination. The 
level of agglutination depends on the 
amount of antigen expressed on RBC 
membranes. This test is difficult to use in 
animals exhibiting RBC auto-agglutination.
◦ The Alvedia Quick Test DEA 1 and 
Alvedia Quick Test A+B blood-typing kits 
(Alvedia, Villeur banne, France) are based 
on immunochromatography; RBCs migrate 
on a membrane and interact with monoclo-
nal antibodies to produce a visible line. A 
second control line appears if the test was 
performed correctly.
◦ RapidVet-H IC Feline uses immunochro-
matography for feline blood typing.
• Several automated blood typing analyzers 
are now commercially available.
• Typing services and/or polyclonal antisera 
are also available for DEA 1, 4, 5 and 7, as 
well as the feline AB system. There is limited 
accessibility to DEA 3, 5 and Dal reagents 
and a complete lack of accessibility to DEA 6, 
DEA 8 and Mik reagents.
• Several genetic variants associated with the 
B and the AB blood groups have been 
identified, representing a promising molecu-
lar diagnostic scheme to genotype cats for the 
AB blood group system and to differentiate 
type A, B and, more recently, AB cats.INDICATIONS
• Screening blood donors and recipients to 
assure blood compatibility prior to transfusion.
• Screening breeding cats to ensure blood-
compatible mates and avoid neonatal 
None
None
None
Hemic, lymphatic, and immune.
  SAMPLE
A 1–2 mL venous blood sample.
EDTA anticoagulant.
Refrigerate for short-term storage.
The physical integrity of RBCs is critical for 
correct results. Ideally, samples should be 
blood typed within 2–3 days of blood 
collection.
PROTOCOL
None
• Dogs—roughly 50% are DEA 1 positive, 
with various degree of antigenic expression 
(Table 1).
• Cats—in North America, most are type A 
(>95% of domestic shorthairs); <5% are type 
B, and <1% are type AB.
None
None
Recent blood transfusion (packed RBCs or 
None

Canine and Feline, Seventh Edition  1499
• Severe anemia may cause false-negative 
results because the number of RBCs may be 
insufficient to agglutinate in response to 
antiserum; this may be circumvented by 
centrifuging the blood sample and removing 
some plasma to concentrate the RBCs prior 
to blood typing.
• Autoagglutination, such as in immune-
mediated hemolytic anemia, precludes typing 
by agglutination-based methods because such 
blood samples will always appear positive. To 
some limits, this may be circumvented by 
washing the RBCs prior to blood typing.
• Marked rouleaux can be mistaken for a 
weak positive reaction with the Rapid Vet-H 
canine and feline blood-typing cards.
Hemolysis of the blood may not allow blood 
typing, because the physical integrity of the 
RBCs is critical for correct results.
Species
• Dogs—DEA 1, 3, 4, 5, 6, 7 and 8, and Dal.
• Cats—feline AB blood groups (type A, B or 
AB) and Mik.
See comments above concerning limited 
availability of some typing reagents.
Breed
• Dogs—breed-associated differences in the 
frequency of blood types are mostly documented 
for DEA 1 (surveys mostly among large breed 
dogs, i.e., canine blood donors). In addition to 
Dalmatians, dogs with the rare Dal-negative blood types were identified in Doberman 
pinschers and shih tzus.
• Cats—significant geographic and breed-
associated differences in the frequencies of 
these blood types have been found. Type B 
domestic cats are uncommon in some 
countries like the United States and 
Switzerland, however, in other countries such 
as Australia, Greece, and T urkey, their 
prevalence can reach up to 36% of the 
non-pedigree feline population (see Table 2).
Age
None
Gender
None
Pregnancy
None
N/A
No
• It is strongly recommended to blood type 
canine blood donors and patients for DEA 
1 prior to transfusion to limit sensitization 
by transfusion, because DEA 1 is the most 
antigenic and clinically significant blood 
type.
• Dal blood typing, in addition to standard 
DEA 1 typing, is recommended in Dalmatians, 
Doberman pinschers and shih tzus, especially 
in previously transfused dogs.• A canine patient negative for a given blood 
type can become sensitized and produce 
specific antibodies against this blood type if 
transfused with positive blood. A subsequent 
transfusion of positive blood may lead to an 
immediate hemolytic transfusion reaction. 
Such transfusion reactions have been 
documented against DEA 1, 4, Dal, and one 
common antigen.
• The sensitization (i.e., the production of 
antibodies in negative dogs) against DEA 4 
or the Dal antigen is particularly challeng -
ing because finding compatible blood may 
be extremely difficult given the high 
prevalence of those blood types in the 
canine population.
• Because of naturally occurring alloantibod-
ies, feline donors and recipients should always 
be blood typed prior to transfusion. As little 
as 1 mL of type A blood can lead to a fatal 
hemolytic transfusion reaction if given to a 
type B cat.
• Type A and AB kittens born to type B queens 
are at risk of developing neonatal isoerythrolysis 
caused by the presence of strong anti-A 
alloantibodies in the colostrum of type B 
queens. The disease is characterized by a severe 
hemolytic anemia and possible nephropathy, as 
well as other organ failures. To avoid neonatal 
isoerythrolysis, it is recommended to blood 
type breeding mates, particularly in breeds with 
a high incidence of type B cats.
• All previously transfused dogs and cats (>4 
days) should be crossmatched, in addition to 
standard blood typing, to look for the 
presence of antibodies before receiving 
additional blood.Table 1
Normal findings in dogs.
Canine Blood Types % Positive % Negative
DEA 1 33–65 35–67
DEA 3 5–24 76–95
DEA 4 87–100 0–13
DEA 5 8–51 49–92
DEA 7 8–82 18–92
Table 2
Cats—type B frequency in North America.
Breeds Type B Frequency in North America (%)
Siamese, Burmese, Tonkinese, Russian blue, Ocicat, Oriental shorthair 0
Maine coon, Norwegian forest, DSH/DLH <5
Abyssinian, Himalayan, Birman, Japanese bobtail, Persian, Somali, Sphinx, Scottish fold 5–25
Exotic and British shorthair, Cornish rex, Devon rex 25–50(continued)  Blood Typing

1500  Blackwell’s Five-Minute Veterinary Consult  
Crossmatch
SYNONYMS
None
SEE ALSO
• Crossmatch (in Appendix X).
• Saline Agglutination Test (in Appendix X).
• DLH = domestic longhair.
• Alvedia: alvedia.com
• Animal Blood Ressources International: 
http://www.abrint.net
• CHUV Blood Bank—Université de 
Montréal: http://chuv.umontreal.ca/
banque-de-sang/• DMS Laboratories: http://www.rapidvet.com
• PennGen Hematology and Typing: https://
www.vet.upenn.edu
Abrams-Ogg ACG. Feline recipient screening. 
In: Yagi K, Holowaychuk M, eds., Manual 
of Veterinary T ransfusion Medicine and 
Blood Banking. Hoboken, NJ: John Wiley 
& Sons, 2016, pp. 129–155.
Acierno MM, Raj K, Giger U. DEA 1 
expression on dog erythrocytes analyzed by 
immunochromatographic and flow 
cytometric techniques. J Vet Intern Med 
2014, 28:592–598.
Blais MC, Berman L, Oakley DA, Giger U. 
Canine Dal blood type: a red cell antigen 
lacking in some Dalmatians. J Vet Intern 
Med 2007, 21:281–286.
Euler CC, Lee JH, Kim HY, et al. Survey of 
two new (Kai 1 and Kai 2) and other blood 
groups in Dogs of North America. J Vet 
Intern Med 2016, 30:1642–1647.
Giger U, Gelens CJ, Callan MB, Oakley DA. 
An acute hemolytic transfusion reaction 
caused by dog erythrocyte antigen 1.1 
incompatibility in a previously sensitized 
dog. J Am Vet Med Assoc 1995, 
206:1358–1362.Goulet S, Blais M-C. Characterization of 
anti-Dal alloantibodies following sensitiza-
tion of two Dal-negative dogs. Vet Pathol 
2017, 1–8.
Goulet S, Giger U, Arsenault J, et al. 
Prevalence and mode of inheritance of the 
Dal blood group in dogs in North America. 
J Vet Intern Med 2017, 31:751–758.
Griot-Wenk ME, Giger U. Feline transfusion 
medicine: blood types and their clinical 
importance. Vet Clin North Am Small 
Anim Pract 1995, 25:1305–1322.
Tocci LJ. Canine recipient screening. In: Yagi 
K, Holowaychuk M, eds., Manual of 
Veterinary T ransfusion Medicine and Blood 
Banking. Hoboken, NJ: John Wiley & 
Sons, 2016, pp. 117–129.
Weinstein NM, Blais MC, Harris K, et al. A 
newly recognized blood group in domestic 
shorthair cats: the Mik red cell antigen. J 
Vet Intern Med 2007, 21:287–292.
Author  Marie-Claude Blais
Consulting Editor  Benjamin M. BrainardBlood Typing  (continued)

Canine and Feline, Seventh Edition  1501
Bone Marrow Aspirate and Biopsy
  BASICS
• Cytologic examination of samples collected 
via bone marrow aspiration (BMA) is 
necessary to assess the presence or absence, 
quantity, and ratio of precursors of the red 
blood cell (RBC), platelet, and white blood 
cell (WBC) lines.
• Cytologic examination is also used in 
staging patients with hematologic and certain 
other malignancies, where bone marrow 
involvement is associated with a higher stage 
• Histologic examination of samples collected 
via bone marrow biopsy (BMB) provides 
information regarding tissue architecture 
within the bone marrow and is an important 
step in evaluating primary bone marrow 
disorders, such as aplastic anemia, nonregen­
erative anemia, myelodysplasia and 
myelofibrosis.
• Poorly prepared smears or inadequately 
harvested core biopsy samples can make 
interpretation difficult.
• BMA:
◦ Identify cell types, quantity, and ratio of 
precursor cells within the bone marrow 
(e.g., when peripheral cytopenias are noted).
◦ Identify the presence of suspected 
◦ Assess bone marrow involvement in 
neoplastic conditions.
◦ Provides information on the cell types 
present but no information on bone 
marrow structure.
• BMB:
◦ Indicated for animals with suspected 
structural bone marrow abnormalities 
(aplastic anemia, non ­regenerative anemia, 
myelodysplasia, myelofibrosis).
None
Hemorrhage is a risk but not expected to be 
clinically significant.
• The procedure has minimal risk.
• Mild discomfort associated with the 
procedure can be alleviated through the use of 
a local anesthetic and heavy sedation or 
anesthesia. If indicated, analgesic agents may 
be provided following the procedure.
Hemic, lymphatic, and immune.  PROCEDURE
Pre-Procedure Medication or Preparation
Hair clipping and aseptic skin preparation are 
indicated prior to BMA or BMB.
Local anesthesia (lidocaine) in conjunction 
with heavy sedation or anesthesia.
• Palpate the desired site of sample collection 
(amenable locations include the head of the 
humerus, iliac crest, and trochanteric fossa; 
the sternum may also be used in some 
animals) and position the animal accordingly.
• Humerus—lateral recumbency with the 
patient’s foreleg rotated externally and 
extended caudally 45°, keeping the leg parallel 
to the table or floor.
• Iliac crest—sternal recumbency with the 
patient’s legs extended forward, rounding the 
lumbosacral area.
• T rochanteric fossa—lateral recumbency.
• Monitor for adequate analgesia and level of 
sedation.
• Monitor for bleeding at the aspiration or 
biopsy site following sample collection.
• If patient is hevily sedated or anesthetized, 
monitors such as pulse oximetry, blood 
pressure, ECG, and capnography may be 
• Sterile 4 × 4 ­inch gauze.
• A no. 11 scalpel blade.
• 1 mL of 2% lidocaine (maximum of 2 mg/
kg, can be diluted to 1% if more volume is 
needed).
• BMA:
◦ A Rosenthal or Illinois BMA needle
◦ A 6­ or 12 ­mL syringe
◦ EDTA solution
◦ A watchglass or glass petri dish
◦ Pipette or hematocrit tubes
◦ Glass slides
• BMB:
◦ A Jamshidi infant needle or pediatric 
BMB needle
◦ A jar containing 10% buffered formalin 
for sample
◦ A cartridge to hold small samples in the 
formalin jar
TECHNIQUE
• BMA or BMB generally requires 2–3 
people: 1–2 to position the animal, monitor 
sedation or anesthesia, and assist with sample 
handling, and the other to collect the sample.• Clip hair from an approximately 5 cm2 area 
over the desired site and perform a surgical 
scrub. After surgical preparation of the site, 
infiltrate the area with 0.5–1.0 mL of local 
anesthetic (e.g., 2% lidocaine), making sure 
to also block the periosteum. Follow with a 
final surgical scrub.
• Make a small stab incision with the no.11 
scalpel blade.
• Insert the bone marrow needle through the 
stab incision made in the skin and subcutan­
eous tissues. Position the needle on the 
periosteum.
• Holding the instrument closely between the 
thumb and index finger and within the closed 
palm, begin to rotate the instrument back 
and forth with gentle pressure until it is 
solidly within the marrow cavity:
◦ Care must be taken to keep the needle 
and instrument in line; avoid rocking the 
needle during its advancement.
◦ Firm adequate placement can be determined 
by the ability to move the limb by moving the 
inserted instrument gently side to side.
• Once positioned in the marrow cavity, the 
cap and stylet are removed and a 6 ­ or 12 ­mL 
syringe (containing 0.5 mL of EDTA, if 
available) is attached to the needle and used 
to aspirate with negative pressure.
• As soon as marrow is seen within the 
syringe, negative pressure is released to 
minimize dilution or contamination of the 
sample with peripheral blood.
• The syringe is then detached and its 
contents emptied in single small drops onto a 
series of glass slides, placing 1 drop per slide 
(alternatively, the contents may be emptied 
into a watchglass or glass petri dish 
containing 0.5–1.0 mL of EDTA; this 
technique reduces the risk of clotting prior to 
slide preparation).
• Working quickly to avoid clotting of the 
sample, the bone marrow drops are smeared 
onto each of the slides (see Fine ­Needle 
Aspiration for slide preparation technique).
• Alternatively, if a watchglass containing 
EDTA is used, individual bone marrow 
particles (identified by a spicule shape) may 
be collected using a pipette or hematocrit 
tube, transferred to the slides, and the sample 
then smeared along the length of the slide.
• Insert the biopsy instrument through the 
• Holding the instrument so the plastic 
handle rests in the palm and the needle 
extends between the index and middle 
fingers, begin to rotate instrument back and 
forth with gentle pressure until it penetrates 
the outer cortex and enters the marrow cavity.

1502  Blackwell’s Five-Minute Veterinary Consult  
• Once securely positioned within through 
the outer cortex, remove the stylet and 
advance the needle 1–2 cm within the 
marrow by continuing to rotate the 
instrument back and forth with gentle 
pressure. At this point, a core of bone marrow 
should be lodged within the hollow needle.
• To break off the core within the needle and 
ensure it is removed along with the instrument, 
sharply twist the instrument several times in a 
clockwise direction, followed by several twists 
in a counterclockwise direction, and then 
firmly rock the instrument in a circular motion 
in one direction and then the other. Finally, 
attach a 6 ­ or 12 ­mL syringe to the end of the 
instrument and apply a single burst of negative 
pressure. The instrument can then be removed 
from the bone by rotation and steady traction.
• Once the instrument is removed, use the 
“shepherd’s crook” stylet inserted retrograde 
though the needle to push the bone marrow 
core biopsy gently out through the top of the 
instrument and place the sample in formalin. 
Small samples should be placed in a tissue 
cassette prior to inserting in formalin jar.
• BMA—air ­dried samples can be stored at 
room temperature, though samples should be 
fixed and stained as soon after collection as 
possible (within 3–7 days) for optimal assess  ­ 
ment of cellular morphology.
• BMB—collected samples should be placed 
in 10% buffered formal for submission to a 
histopathology laboratory.
• A peripheral blood sample should be 
collected and submitted at the time of either 
BMA or BMB.
• Monitor for evidence of mild superficial 
hemorrhage at the BMA or BMB site.
• Monitor for evidence of discomfort at the 
BMA or BMB site or lameness on the 
sampled leg.
None
None
None
None
Immediate
• Bone marrow should be evaluated by a 
trained pathologist.• Sample should be evaluated for:
◦ Cellularity (normal range, 25% fat and 
75% cells to 75% fat and 25% cells; varies 
according to age).
◦ Megakaryocyte series (normal range, 
approximately 4–50 megakaryocytes per 
spicule).
◦ Erythrocyte series (abundance, 
proportions, morphology).
◦ Granulocytic series (abundance, 
◦ Myeloid/erythroid ratio (normal range, 
0.75:1 to 2:1).
◦ Presence of organisms (e.g., Histoplasma 
capsulatum, Leishmania donovani, 
Toxoplasma gondii, Cytauxzoon felis, 
Ehrlichia  spp.)
◦ Presence of erythrophagocytosis, 
plasmacytosis, iron ­containing pigments, 
neoplastic cell infiltration, and myelo ­ 
fibrosis.
• Decreased overall cellularity.
• Increases or decreases in megakaryocyte 
numbers.
• Abnormal numbers, proportions, or 
morphology of erythrocyte or granulocyte 
series.
• Presence of infectious organisms.
• Evidence of erythrophagocytosis, plasmacy­
tosis, or decreased iron ­containing pigments.
• Neoplastic cell infiltration.
None
• Administration of immunosuppressive 
therapies (as for suspected immune ­mediated 
cytopenias) prior to sample collection may 
alter interpretation.
• Administration of corticosteroids or other 
chemotherapeutic agents prior to sample 
collection may alter the presence or number 
of neoplastic cells.
None
• Inadequate sample collection; animals with 
myelofibrosis may have underwhelming BMA 
and difficult to obtain BMB.
• Excessive aspiration with BMA may lead to 
dilution or contamination of the sample with 
peripheral blood.
Species
NoneBreed
Some breed ­related variability; for example, 
increased hematocrit, mild thrombocytopenia, 
mild leukopenia may be seen in greyhounds.
Age
Normal bone marrow cellularity decreases 
with age: samples from juvenile, adult, and 
geriatric animals contain approximately 25% 
fat and 75% cells, 50% fat and 50% cells, 
and 75% fat and 25% cells, respectively.
Gender
None
Pregnancy
None
via BMA is an important step in assessing the 
presence or absence, quantity, and ratio of 
precursors of the RBC, platelet, and WBC 
lines in patients with increases or decreases in 
peripheral blood cell counts.
• Assessment can support a diagnosis and 
prognosis in animals with cytopenias and 
hematologic and certain other malignancies.
• BMB provides additional information 
regarding tissue architecture within the bone 
marrow.
A CBC should be performed in conjunction 
with BMA and BMB.
SYNONYMS
None
SEE ALSO
• Bone Marrow Aspirate Cytology: 
Microscopic Evaluation (in Appendix X).
• Myelodysplastic Syndromes.
• BMA = bone marrow aspiration.
• BMB = bone marrow biopsy.
Cowell RL, Tyler RD, Meinkoth JH. 
the Dog and Cat. St. Louis, MO: CV 
Mosby, 1999.
Author  Laurel E. Williams
Consulting Editor  Benjamin M. BrainardBone Marrow Aspirate and Biopsy  (continued)

Canine and Feline, Seventh Edition  1503
Bone Marrow Aspirate Cytology: Microscopic Evaluation
  BASICS
Tissue
Bone marrow is the major hematopoietic 
organ of the mammalian body, and its 
examination aids in evaluating various 
hematologic disorders. The most common 
indication for its microscopic evaluation is a 
complete blood count (CBC) abnormality that 
cannot be readily explained by a good medical 
history or by physical examination, chemistry 
profile, and/or other diagnostic procedures. In 
addition, bone marrow evaluation may aid in 
monitoring disease progression or response to 
therapy, determination of disease prognosis, 
and staging of certain neoplasms. Finally, body 
iron stores can be estimated, particularly if 
special stains are used, and occult infectious 
agents may be identified. A CBC collected 
within 24 hours of marrow collection is 
imperative for accurate interpretation of 
findings.
In young animals, active hematopoiesis 
occurs throughout the skeleton in both the 
long bones (e.g., humerus, femur) and flat 
bones (e.g., ribs, pelvis). However, active 
hematopoiesis in normal adult animals is 
restricted to the flat bones and extremities of 
the long bones (e.g., proximal humerus or 
femur); the central area of the long bones is 
composed predominantly of adipose tissue. 
Furthermore, even the hematopoietically 
active regions of adult animals contain a 
higher percentage of fat compared to these 
areas in young animals. Knowledge of the 
age-related anatomic distribution of hemato -
poietic tissue is imperative so that an appropri -
ate, representative specimen is collected.
Active hematopoietic tissue is highly 
vascular and the spaces between vascular 
sinuses are filled with hematopoietic cells. 
The hematopoietic areas are bordered by the 
endothelium lining the vascular sinuses and 
are given structural scaffolding by adventitial 
cells. Hematopoietic tissue is predominantly 
composed of megakaryocyte, erythrocyte, 
granulocyte, and monocyte cell precursors in 
various stages of maturation. Low numbers of 
resident macrophages, lymphocytes, plasma 
cells, and mast cells, as well as a variable 
amount of adipose tissue, are also normally 
present.
Collection of both aspirates and core 
biopsy specimens is technically simple (see 
Bone Marrow Aspirate and Biopsy). Aspirate 
specimens allow detailed analysis of cell 
populations, individual cell identification, 
and morphologic evaluation and are more amenable to cytochemical staining and 
immunocytochemistry. However, aspirates 
do not preserve architecture and may not be 
representative of the marrow as a whole. 
Myelofibrosis, regardless of the cause and, to 
a certain extent, the severity, often exfoliates 
poorly and may yield an insufficient 
specimen, so a core biopsy is crucial in these 
instances. Core biopsies have a longer turn  - 
around time and are more expensive, but 
their utility lies in the preservation of tissue 
architecture and more accurate impression 
of overall cellularity. Additionally, cell 
arrangement, necrosis, infiltrative patterns, 
myelofibrosis, absolute megakaryocyte 
numbers, and quantification of iron stores 
can be better assessed in a core biopsy 
sample.
Prior to laboratory submission, a slide 
should be stained to assess whether it contains 
an adequate number of well-preserved 
hematopoietic unit particles or spicules. 
Spicules grossly appear as fatty streaks on 
unstained preparations and as intensely 
staining blue areas on stained preparations. If 
the slide is satisfactory, the stained and, 
preferably, additional unstained slides may 
then be sent to a diagnostic laboratory. Bone 
marrow aspirates collected into EDTA may 
also be submitted to the lab so that additional 
slides may be prepared.
• Peripheral blood abnormalities.
• Unexplained, persistent decreases in cell 
counts, including non- or poorly regenerative 
anemia, neutropenia, or thrombocytopenia.
• Unexplained, persistent elevations in cell 
counts.
• Atypical cells in peripheral blood.
• Clinical staging of malignancy.
• Unexplained hyperproteinemia or 
monoclonal gammopathy.
• Unexplained hypercalcemia.
• Fever of unknown origin, especially in 
searching for occult disease, including 
• Assessment of body iron stores.
• Suspicion of osteomyelitis or infiltrative 
or proliferative bone marrow disease as may 
or may not be suggested by diagnostic 
imaging.
• A bone marrow core biopsy is indicated 
when repeated aspiration attempts, 
particularly if different sites are sampled, fail 
to yield adequate marrow samples.
None
• Risks related to heavy sedation or anesthesia 
necessary for procedure.
• Fracture of bone already compromised by 
infiltrative disease or other pathology.CLIENT EDUCATION
• Interpretation of findings typically 
contingent upon CBC collected within 24 
hours.
• Inherent pathology such as myelofibrosis 
can result in yield of insufficient sample 
(biopsy preferred to aspirate).
Hemic/lymphatic/immune
  SAMPLE
Marrow from proximal humerus or femur, 
wing of ilium, or sternum. Can be collected 
into EDTA, or directly prepared onto glass 
microscope slides.
T ransport slides at room temperature in an 
appropriate protective slide container. Marrow 
collected into EDTA should be maintained 
chilled as with CBC blood samples.
Store slides at room temperature, protected 
from light. Avoid exposure to extreme 
temperatures, humidity, and formalin fumes 
(submit bone marrow core biopsies in 
separate specimen bag). Retain unstained 
slides for possible ancillary testing.
• Stained slides are stable for months to years.
• Unstained slides are stable for 1 week or 
more.
PROTOCOL
• Subjective evaluation of the marrow begins 
with a low-power (40– 100×) magnification 
of overall cellularity, megakaryocyte numbers, 
and iron content.
• Evaluate cellularity—identify multiple 
large, intact particles and compare the 
proportion of dark blue-staining hematopoietic 
tissue to the proportion of colorless adipose 
tissue within the particle to determine a 
rough percentage. Estimates of cellularity will 
be inaccurate if the number of particles on 
the slide is low. Good-quality bone marrow 
core biopsies typically give a more accurate 
• Assess megakaryocytes—approximately 2–7 
megakaryocytes are normally associated with 
each particle, although the exact number 
varies by species and the technique used to 
make the cytologic preparation. Megakaryo -
cytes are the largest of the hematopoietic cells 
and are easily seen at low-power magnification. 
Mature megakaryocytes should predominate; 
they have abundant pale basophilic cytoplasm 
with fine magenta granules and 8 or more 
nuclei fused into a dense, lobulated mass.

1504  Blackwell’s Five-Minute Veterinary Consult  
• Assess iron stores—a few small clumps of 
brown to black material per particle 
representing iron stored in the form of 
hemosiderin are routinely identified in the 
bone marrow of normal dogs. Prussian blue 
reaction may be used to confirm the presence 
or absence of iron, but typically is not 
necessary. Stainable iron is usually absent in 
normal bone marrow from healthy cats.
• At high power (500– 1000× magnification), 
attempt a general assessment of cell distrib -
ution (M/E ratio).
• Erythroid precursors appear as smaller, 
darker cells. They generally have darker 
basophilic cytoplasm and round nuclei with 
condensed chromatin.
• Myeloid precursors are larger and paler with 
light blue cytoplasm that may contain 
magenta primary granules or secondary 
granules with a round, indented, or U-shaped 
nucleus. Secondary granules can be eosino -
philic, basophilic, or nonstaining (i.e., in 
neutrophil precursors).
• In healthy animals, there are approximately 
equal numbers of erythroid and myeloid 
precursors that should be overwhelmingly 
predominated by the later stages.
• Other cells, such as macrophages, lympho -
cytes, plasma cells, and mast cells, are 
normally found in low numbers.
• If any single type of cell appears to 
predominate, or if unusual morphologies are 
encountered, evaluation by a board-certified 
pathologist is recommended.
• Cellularity (adults)—33%–66% hemato -
poietic cells; remaining percentages consist of 
adipose tissue.
• Megakaryocytes—2–7 megakaryocytes per 
spicule; highly variable depending on the 
technique used to prepare the slide and overall 
sample yield (e.g., presence of spicules).
• M/E ratio—0.75–2.53 (dogs) and 
1.21–2.16 (cats).
Values above or below the reference ranges.
None
NoneDrugs That Alter Physiology
Some drugs have been associated with toxic 
effects on hematopoietic cells, including 
diethylstilbestrol, phenylbutazone, 
chloramphenicol (especially cats), 
sulfadiazine, methimazole, albendazole, 
phenobarbital, and griseofulvin.
• Low yield aspirates (e.g., overall poor 
cellularity or lacking sufficient spicules) may 
occur with hypocellular marrow, stromal 
reactions (e.g., myelofibrosis), and neoplasms 
resulting in myelophthisis (e.g., mesenchymal 
neoplasms).
• Chronic blood loss anemia may lead to 
megakaryocytic hyperplasia despite a normal 
platelet count.
• Inappropriate collection site (i.e., area of 
bone not actively involved in hematopoiesis).
• Insufficient number of particles/low yield 
aspirate.
• Excessive pressure when preparing cytologic 
slides or delayed collection (>30 minutes) 
after animal’s death may result in lysed cells.
• Delayed processing or exposure of cytology 
to formalin fumes will alter staining.
• Clotted aspirates will have reduced 
cellularity and skewed differential cell counts.
Species
• Cats normally lack stainable iron, regardless 
of their age.
• Subtle variations in differential cell 
percentages (e.g., cats may have slightly more 
numerous lymphocytes than dogs).
Breed
None
Age
• Young animals have active hematopoietic 
tissue throughout long and flat bones. Adult 
animals exhibit the most active hematopoiesis 
in their flat bones and the extremities of their 
long bones. The central area of long bones 
contains abundant adipose tissue and very 
little active hematopoietic tissue.
• Older dogs often have abundant stainable 
iron, whereas younger dogs do not.
Gender
None
Pregnancy
None
N/AValid If Run in a Human Lab?
Yes
• Cytologic findings must be interpreted in 
light of the medical history, clinical findings, 
CBC, and results from other diagnostic tests 
and procedures.
• A bone marrow aspirate cannot be adequately 
interpreted without a concurrent CBC, 
particularly with regard to assessment of the 
M/E ratio.
• Concurrent CBC (obtained within the last 
24 hours).
• Blood film morphologic assessment of 
circulating blood cells.
• Bone marrow core biopsy sample.
• Immunocytochemistry, immunopheno -
typing, and cytochemical stains to determine 
clonality and lineage of abnormal cells 
identified in marrow, including PARR and 
flow cytometry.
• FeLV IFA or PCR on bone marrow for 
occult FeLV infection if peripheral blood 
ELISA is negative.
• Serology or PCR testing for arthropod-
vectored diseases (e.g., Ehrlichia  spp.).
• Serum protein electrophoresis to assess 
hyperglobulinemia.
SYNONYMS
None
SEE ALSO
• Bone Marrow Aspirate and Biopsy (in 
Appendix X).
• Ehrlichiosis
• Epo = erythropoietin.
factor.
• M/E or M:E ratio = myeloid/erythroid 
ratio.Bone Marrow Aspirate Cytology: Microscopic Evaluation  (continued)

Canine and Feline, Seventh Edition  1505
Table 1
Causes of abnormal values.
Marrow Component High Values (Hyperplasia) Low Values (Hypoplasia)
Iron stores Hemolysis
Previous blood transfusions
Erythroid hypoplasia
Parenteral iron supplementationIron deficiency
Overall cellularity Response to peripheral demand (see 
specific lineages)
Anemia and/or hypoxemia (erythroid 
hyperplasia)
Neutrophilic inflammation (granulocytic/
myeloid hyperplasia)
Thrombocytopenia (megakaryocytic 
Neoplasia, primary or metastatic, and 
other myeloproliferative disordersGeneralized hypoplasia/aplasia
Certain antibiotics (e.g., trimethoprim-sulfadiazine, cephalosporins, 
chloramphenicol)
Estrogens, exogenous or endogenous (dogs and ferrets)
Anticonvulsants (e.g., phenobarbital)
Phenylbutazone (dogs)
Griseofulvin (cats)
Thiacetarsamide, meclofenamic acid, quinidine (a possible cause in dogs)
Albendazole
Radiation
Myelonecrosis (may have degenerate cells)
Myelofibrosis
Canine parvovirus infections (erythroid and myeloid hypoplasia)
FeLV infection (especially with feline parvovirus infection)
Severe Ehrlichia canis infection
Primary immune-mediated destruction of hematopoietic precursor cells
Erythroid Effective erythroid hyperplasia in response 
to anemia and/or hypoxemia
Ineffective erythroid hyperplasia
Severe iron deficiency
Folate deficiency
Some myeloproliferative and 
myelodysplastic disorders
Congenital dyserythropoiesis
Immune-mediated destruction of late 
erythroid precursors
Response to Epo treatment
Renal or other Epo-secreting neoplasmsSelective erythroid hypoplasia
Parvovirus vaccination?
Gray collies with cyclic hematopoiesis (followed by erythroid hyperplasia)
Chloramphenicol (especially in cats)
Lymphoid malignancy
Immune-mediated destruction of early erythroid precursors
Immune mediated, associated with recombinant Epo therapy
FeLV type C infection
Dogs with idiopathic myelofibrosis
Anemia of inflammatory disease (concomitant granulocytic hyperplasia)
Endocrinopathies (e.g., hypothyroidism, hypoadrenocorticism, 
hypopituitarism, hypoandrogenism; usually does not increase M/E ratio)
Chronic renal disease (usually does not increase M/E ratio)
Neutrophilic myeloid 
precursorsEffective myeloid hyperplasia
Proliferative response to neutrophilic 
inflammation
Dogs with β2-integrin adhesion molecule 
deficiency
Gray collies with cyclic hematopoiesis
Ineffective myeloid hyperplasia
Myelodysplastic disorders
Acute myelocytic leukemia
Neutropenic cats with FeLV and/or FIV 
infection
Immune-mediated targeting myeloid 
precursors
Response to G-CSF treatment
Paraneoplastic neutrophiliaSelective myeloid hypoplasia Azathioprine (cats)
Griseofulvin (risk increased in FIV-positive cats)
Methimazole (reported in cats)
Recombinant G-CSF from another species (similar to recombinant Epo-
induced anemia)
Canine and feline parvovirus infection (concurrent erythroid hypoplasia)
Gray collies with cyclic hematopoiesis (followed by neutrophilic hyperplasia)
FeLV-induced cyclic hematopoiesis
Immune-mediated targeting early myeloid precursors
(Continued )(continued)  Bone Marrow Aspirate Cytology: Microscopic Evaluation

1506  Blackwell’s Five-Minute Veterinary Consult  
http://eclinpath.com/atlas/bone-marrow/
Grindem CB, Neel JA, Juopperi TA. 
Cytology of bone marrow. Vet Clin North 
Am Small Anim Pract 2002, 
32:1313–1374.Harvey JW. Veterinary Hematology: 
A Diagnostic Guide and Color  
Atlas. St. Louis, MO: Elsevier/Saunders, 
2012.
Ames, IA: Wiley-Blackwell, 2008.Author  Rebekah G. Gunn-Christie
acknowledge the prior contribution of John 
W. Harvey.Table 1
Causes of abnormal values ( continued )
Eosinophilic myeloid 
precursorsParasitic disease (especially nematode 
and fluke infestation)
Inflammation of organs rich in mast cells 
(skin, lung, intestine, uterus)
IgE-mediated allergic hypersensitivity 
reactions
Eosinophilic granulomas
Hypereosinophilic syndrome
Eosinophilic leukemia
Mast cell and some other tumors 
(uncommon to rare)Eosinophilic hypoplasia not a clinically recognized entity
Basophils Usually associated with same disorders 
causing eosinophilia
Dirofilariasis (dogs and cats)
Lymphomatoid granulomatosis
Basophilic leukemia
Myelodysplastic disordersBasophilic hypoplasia not a clinically recognized entity
Megakaryocytes Primary and secondary immune-mediated 
thrombocytopenia
Ongoing intravascular coagulation
Hypersplenism
Vascular injury
Infections (e.g., early Ehrlichia canis) and 
toxicoses causing platelet destruction
ThrombocythemiaSelective megakaryocytic hypoplasia
Immune-mediated
Drug-induced: hypoplasia usually generalized, but megakaryocytes may be 
specifically decreased (e.g., dapsone [in dogs] and ribavarin [in cats, 
concomitant erythroid hypoplasia possible])
Meclofenamic acid
Phenylbutazone
Trimethoprim-sulfadiazine
ChemotherapyBone Marrow Aspirate Cytology: Microscopic Evaluation  (continued)

Canine and Feline, Seventh Edition  1507
Complete Ophthalmologic Exam
  BASICS
Diagnostic examination
• Step-wise assessment of the adnexal and 
ocular components, their structural and 
neurological function, and their potential 
affects on ocular comfort and vision.
• Various diagnostic tests and equipment 
are used as part of the eye exam, and 
familiarity with the normal values and 
ocular anatomy will allow for recognition 
of early or subtle changes and assist in 
diagnosis and treatment of discrete 
ophthalmic conditions.
• Indicated as part of a wellness examina -
tion or as part of a health screening in 
• Iindicated when the patient is presented 
for ocular discomfort, an abnormal ocular 
appearance, or changes in vision. As part of 
diagnostic testing for an unknown illness, 
an eye exam may reveal ocular manifesta -
tions of systemic disease.
Individual steps of the eye exam may be 
contraindicated, such as pharmacological 
mydriasis in a patient with elevated 
intraocular pressure or tonometry in a 
patient with a fragile globe (deep corneal 
ulcer, perforation or laceration).
• A complete eye exam is a noninvasive 
procedure; however, some of the ancillary 
diagnostic tests require direct contact with the 
cornea or application of ophthalmic drugs:
◦ Risk of drug hypersensitivity to topical 
anesthetic or mydriatic agents, resulting 
in conjunctival hyperemia, chemosis, 
ocular pruritis, blepharospasm, or 
photophobia.
◦ Contact with the cornea while 
performing tonometry or tear assessment 
could result in corneal epithelial erosions. 
While these complications are rare, they 
can cause ocular discomfort.
• The eye exam is important in determin -
ing the cause of ocular discomfort or 
changes in ocular appearance or vision, and 
may be a key component in recognition of 
local or systemic infection, inflammation or 
• The need for a referral to a veterinary 
ophthalmologist for more extensive 
diagnostic testing, medical therapy, or 
surgical procedures may be indicated based 
on the findings.• Detection of certain ocular abnormalities 
in breeding animals may suggest inherited 
conditions, and could affect reproductive 
Ocular and neuro-ophthalmic.
  PROCEDURE
Pre-Procedure Medication, Equipment 
or Supplies (Figure 1)
Prior to the eye exam, the following 
medications, instrumentation, and 
accessory diagnostic tools should be 
• Topical ophthalmic anesthetic, such as 
proparacaine HCl 0.5% ophthalmic 
solution.
• Topical ophthalmic mydriatic, such as 
tropicamide 1% ophthalmic solution.
• Eye wash/eye irrigating solution.
• Schirmer tear test strips.
• Fluorescein stain ophthalmic strips or 
solution.
• Tonometer (rebound or applanation).
• Ophthalmoscope handle with direct lens 
attachment, including cobalt blue filter, 
and a Finoff transilluminator tip.
• Hand-held condensing lens (20D, 28D, 
30D or 2.2 pan retinal lenses) for indirect 
ophthalmoscopy.
• Magnifying loupes, such as OptiVISOR.
Except in the case of an extremely fractious 
animal, sedation should be avoided. Most 
sedative agents will lower tear production, 
in addition to making examination of the 
eye more difficult due to elevation of the 
nictitating membrane and ventral rotation 
of the globe.
• Good restraint of the patient is key to a 
thorough eye exam. Ideally, the patient 
should be positioned on an exam table in 
sternal recumbency.
• Special attention to minimal manipula -
tion of the eyelids is important when 
assessing the eyelid and globe position, and 
also when obtaining intraocular pressures 
to avoid falsely elevated readings.
TECHNIQUE
• The complete eye exam, similar to a 
physical exam, is performed in a step-wise 
fashion, typically in the same order each time 
to avoid missing subtle abnormalities.
• The initial part of the exam is performed 
from a distance and without touching the 
patient, while later steps require good 
restraint and minimal movement from the 
patient.• A thorough patient medical and ocular 
history is important to obtaining an 
accurate diagnosis and appropriate 
treatment plan:
1. Observation of the patient prior to 
restraint may allow for detection of behaviors 
suggestive of visual deficits. Interactions 
between the pet and objects in the exam 
room may reveal hesitancy or loss of visual 
cues in an unfamiliar environment. If visual 
deficits are suspected, consider additional 
tests, such as maze testing using obstacles 
placed in the patient’s path or cotton-ball 
tracking to investigate further. These tests can 
be done in both room lighting and dim 
lighting conditions to explore the possibility 
of decreased night vision or nyctalopia.
2. Once the patient has been adequately 
restrained, the face and eyes should be 
assessed for symmetry of adnexal and 
periocular structures (e.g. muscles of 
mastication, palpebral fissure size), in 
addition to globe size and position, and 
pupil symmetry. The Finoff transillumina -
tor can be held at an arm’s length, close to 
the examiner’s eye, and retroillumination 
using the tapetal reflex will allow for good 
assessment of pupillary size and symmetry. 
Palpation of the tissues around the orbit 
may reveal muscle atrophy, boney prolifera -
tion or orbital cellulitis. The globe itself 
should easily retropulse into the orbit 
behind closed lids. Retropulsion may be 
important in helping to distinguish 
exophthalmia from buphthalmia. An oral 
exam is indicated for patients with 
suspected orbital disease.
3. The neuro-ophthalmic exam includes 
assessment of cranial nerves (CN) II–VII.
a. The palpebral reflex is performed by 
gently touching at the temporal and 
then nasal canthus, and observing the 
eyelids to close. Incomplete blink may 
suggest either a decrease in sensation 
(CN V) or motor function (CN VII) or 
lagophthalmia, such as is seen in 
brachycephalic dogs.
b. The menace response, a crude 
estimation of vision, assesses CN II and 
CN VII. This is a learned response present 
in animals older than 8–12 weeks of age. 
This test is performed by making a swift 
“menacing gesture” with a closed hand 
toward the eye and watching for a blink 
response ± slight withdrawal of the head. 
Be careful not create movements of air or 
brush against hairs around the eye that 
could stimulate a response that is tactile 
rather than visual. By covering each eye in 
turn, a more individual assessment of the 
contralateral eye can be performed.
c. The pupillary light reflex (PLR) can 
be appraised after noting for symmetry 
in size, shape and position of the pupils 
(e.g., anisocoria, dyscoria). A bright

1508  Blackwell’s Five-Minute Veterinary Consult  
light from a Finoff transilluminator 
should stimulate a direct response (pupil 
constriction) in the ipsilateral eye and a 
slightly less robust consensual response 
in the contralateral eye. The PLR should 
be assessed for each eye, with notation 
of both direct and consensual responses. 
PLRs can be complete, incomplete, 
delayed, or absent. Any abnormal 
response may suggest pathology in the 
retina, optic nerve, or PLR pathway, 
including CN III or iris sphincter 
muscles. This test does not assess the 
visual pathways in the brain.
d. The dazzle reflex is also performed 
with a bright light directed towards each 
eye, with a reflexive response of 
blinking. This test assesses CN II, CN 
VII and the visual pathways in the 
brain. Although a positive test does not 
correlate directly with vision, a negative 
dazzle reflex does give a poor prognosis 
for return to vision.
e. The presence of strabismus or 
nystagmus or lack of ability to move the 
globe may indicate oculomotor 
(neurologic or extraocular muscle) 
deficits and could indicate either central 
or peripheral nervous system disorders 
or orbital disease. Mild esotropia and pronounced physiologic nystagmus are 
common in Siamese cats.
4. The accessory diagnostic tests are 
performed next.
a. The Schirmer tear test (STT) is a 
measurement of both basal and reflex 
tear production. This is performed by 
placing the notched end of STT strip 
into the conjunctival fornix in the 
lateral 2/3 of the lower lid. Care is taken 
not to handle this portion of the strip to 
avoid contamination with oil or debris 
from the examiners’ fingers. Placement 
of a slight bend at the notch through 
the protective plastic sleeve may help to 
keep it in position. The strip should 
remain in the fornix for 60 seconds, 
removed, and immediately read out. A 
normal tear production in a dog is 
approximately 18 ± 3 mm/min. Tests 
reading below 15 mm/min in combina -
tion with clinical signs of keratocon -
junctivitis (e.g., mucoid discharge, 
conjunctival hyperemia, corneal 
pigmentation or vascularization) may 
signal quantitative tear film abnormali -
ties (keratoconjunctivitis sicca [KCS]). 
Normal STT readings with similar 
clinical signs may indicate a qualitative 
tear film abnormality.b. Following the STT, the intraocular 
pressure (IOP) should be estimated. If 
an applanation tonometer is to be used, 
application of topical anesthetic 20–30 
seconds prior to testing is necessary. A 
rebound tonometer does not require 
topical anesthetic. The examiner should 
be familiar with the instrument’s 
requirement for calibration, instructions 
for use, and also understand the 
measurement confidence interval (CI 
85–95%) for each reading. The patient 
should be gently restrained with 
minimal pressure on the neck and 
eyelids to allow for the most accurate 
readings. Tight muzzles may interfere 
with normal IOP readings. Most devices 
require 5-6 contacts with the cornea to 
calculate an average estimated IOP . Any 
reading with <95% CI or IOP >20 
mmHg should be repeated to ensure 
accuracy. Consider additional testing if 
glaucoma is suspected.
c. Following IOP measurement, one 
drop of fluorescein stain can be applied 
to look for evidence of corneal epithelial 
erosions or ulceration. The stain should 
be gently rinsed with eye wash or saline, 
and the cornea should be evaluated with 
the cobalt blue filter of the ophthalmo -
scope head. Stain uptake will appear 
Figure 1 .
From top left: Eye wash irrigating solution, proparacaine HCl 0.5% ophthalmic solution, tropi -
camide 1% ophthalmic solution, TonoPen Avia® applanation tonometer, TonoVet Plus® rebound 
tonometer, Volk 2.2 Pan Retinal hand-held condensing lens and case, direct ophthalmoscope head 
attachment, and ophthalmoscope handle with Finoff transilluminator attachment. Source: 
Lawrence P . TilleyComplete Ophthalmologic Exam  (continued)

Canine and Feline, Seventh Edition  1509
bright green in the blue light, and 
indicates loss of the corneal epithelium. 
Corneal ulcers should be treated 
accordingly based on features such as 
chronicity, depth, and evidence of 
infection. With any deep corneal ulcer, 
the eye should be considered fragile and 
at risk of perforation.
d. If the eye exam is normal to this 
stage, a drop of tropicamide, an 
ophthalmic mydriatic agent, may be 
applied topically to dilate the pupil. 
Dilation will allow for a comprehensive 
examination of the lens and fundus. In 
patients with an elevated IOP , iris 
pigment changes, iris masses or marked 
irregularities, suspected lens instability, 
or PLR abnormalities, a consultation 
with an ophthalmologist may be 
recommended prior to dilation.
5. The next step in the eye exam is a survey 
of the adnexal structures- the eyelids, 
including the nictitating membrane, 
conjunctiva, and nasal-lacrimal system. The 
Finoff transilluminator can be used to 
examine these structures. Additional 
magnification in the form of magnifying 
loupes may be required.
a. The eyelids should be inspected for 
abnormalities in position or length (e.g. 
entropion/ectropion, ptosis), irregulari -
ties, thickening or discoloration (e.g. lid 
masses, blepharitis), or aberrant hairs 
(distichia, ectopic cilia, trichiasis). The 
eyelid margin should be smooth and in 
contact with the cornea help to evenly 
distribute the tear film. The meibomian 
gland openings should be apparent as 
gray dots along the lid margin, but 
should not be inflamed or have excess 
b. The conjunctiva lines the eyelids 
(palpebral conjunctiva), the globe 
(bulbar conjunctiva) and nictitating 
membrane. The conjunctiva, a mucous 
membrane, should be smooth, pink and 
moist without excessive discharge. If 
conjunctivitis is suspected, additional 
testing can be considered.
c. Examination of the nictitating 
membrane is enhanced when the globe 
is gently retropulsed so that this third 
eyelid will passively elevate. If there is 
suspicion of foreign material in the eye, 
the leading edge of the nictitating 
membrane can be grasped with 
atraumatic forceps, such as von Graefe 
forceps, following the application of 
topical anesthetic. Any swelling or 
protrusion of the third eyelid, its gland 
or cartilage should be further 
investigated.
d. The lacrimal puncta are located near 
the medial canthus, just inside the eyelid margin of the upper and lower 
eyelids. The openings should lack 
discharge. Chronic epiphora or 
mucopurulent discharge may be 
suggestive of an obstruction of the nasal 
lacrimal system or dacryocystitis. A 
positive Jones test (a drop of fluorescein 
stain placed on the cornea observed 
exiting the ipsilateral nares) confirms 
patency of the nasal–lacrimal system.
6. Examination of the cornea can be 
performed with the Finoff transilluminator, 
but magnification using the direct 
ophthalmoscope is ideal for noting fine 
details. The corneal surface should be 
smooth and transparent, with a lustrous 
tear film, and no evidence of blood vessels, 
pigment, fibrosis, edema or other opacity. 
Commonly, tear film abnormalities are the 
cause of corneal changes in the dog. The 
STT is important in ruling out dry eye 
disease. The fluorescein stain test can assess 
for corneal ulceration. Keratitis, or 
inflammation of the cornea, is usually 
represented by vascularization, corneal 
infiltrate, or pigmentation, and can be 
ulcerative or non-ulcerative. Various 
corneal dystrophies, corneal degeneration 
or other keratopathies may also be present.
7. The anterior chamber should be 
evaluated for appropriate depth and clarity. 
The slit beam of the direct ophthalmoscope 
can be used to look for flare (protein or 
cellular debris) in the anterior chamber 
causing the Tyndall effect (scattering of 
light causing a hazy beam to appear in the 
normally clear aqueous). The slit beam 
should be focused on the cornea, and there 
should be no evidence of light between the 
cornea and iris face/anterior lens capsule in 
the normal eye. Any opacity in the anterior 
chamber should be further assessed, as 
anterior uveitis is most likely the cause. 
Strands of vitreous may be seen in the 
anterior chamber in patients with lens 
8. The iris is most easily examined prior to 
dilation. The direct ophthalmoscope can be 
used for magnification. The iris face is not 
completely smooth, and the major arterial 
circle runs along the periphery, close to the 
iris base. This is especially apparent in 
animals with light colored irides. Irregul -
arities in the iris, such as excess pigment or 
pigment loss, abnormal blood vessels, fine 
strands of tissue (e.g. persistent pupillary 
membranes) or iridal masses should be 
noted prior to pharmacological dilation. 
The pupil margin should be smooth, 
although some patients have a slightly 
darker but normal “pupillary ruff.” A 
moth-eaten or ragged edge to the pupil 
margin, especially in conjunction with 
decreased miosis during PLR assessment, may indicate iris atrophy. A patient with 
uveitis often has a miotic pupil at rest and 
may have evidence of fine blood vessels on 
the iris face (rubeosis iridis), in addition to 
flare in the anterior chamber.
9. The lens should be examined with the 
pupil dilated to allow for the most 
comprehensive assessment. The direct 
ophthalmoscope can be used for magnifi -
cation to look at fine details in the lens, but 
the Finhoff transilluminator is good to 
assess the overall appearance. The lens and 
lens capsule should be smooth and 
transparent. Any opacity within the lens 
that blocks the tapetal reflex is considered a 
cataract, while nuclear sclerosis is simply 
the more densely compacted nuclear lens 
fibers noted in older animals. Nuclear 
sclerosis does not block the light passing 
through to the posterior segment or light 
bouncing off the tapetum during retroillu -
mination, and a fundic exam can be easily 
performed in a patient with nuclear sclerosis; 
however, varying degrees of cataract may 
make the fundic exam more difficult or 
impossible. Any lens instability should be 
noted, as lens subluxation or luxation are a 
risk for development of glaucoma. With 
early lens instability, an aphakic crescent 
may be noted, when some of the zonules 
holding the lens in place are lost, allowing 
the lens to shift in position. This may 
appear as a brighter tapetal reflection along 
the equator of the lens. In a normal patient, 
the equator, or most peripheral aspect of 
the lens, should not be visible. Occasionally, 
vitreous can be seen coming forward into 
the anterior chamber in the region of the 
aphakic crescent.
10. The posterior segment exam can be 
performed with the direct ophthalmoscope, 
but a more panoramic view of the fundus is 
best achieved using indirect ophthalmoscopy.
a. First, using the Finoff transillumina -
tor, the region just posterior to the lens 
should be surveyed for any opacity. 
Anterior vitreous changes causing 
opacities include vitreal degeneration 
(e.g., asteroid hyalosis, syneresis). Other 
changes in the vitreous could be due to 
congenital abnormalities, hemorrhage, 
or intraocular neoplasia.
b. For the best view of the fundus, 
including retinal blood vessels, tapetum 
and non-tapetum, and optic disc, a

and non-tapetum, and optic disc, a 
hand-held condensing lens (20D, 28D, 
30D or 2.2 pan retinal lens) and Finoff 
transilluminator are used for indirect 
ophthalmoscopy. The examiner sits or 
stands at about one arm’s length from the 
patient while an assistant stabilizes the 
head and gently retracts the eyelids. The 
Finoff light source is held close to the 
examiner’s eye, directed at the patient’s eye. (continued)  Complete Ophthalmologic Exam

1510  Blackwell’s Five-Minute Veterinary Consult  
A bright tapetal reflex will help guide the 
examiner to the appropriate placement of 
the lens, about 5–6 cm from the patient’s 
eye. The lens should be moved just 
slightly either towards the examiner or 
towards the patient until the fundic image 
is focused on the lens. The examiner 
should make slight adjustments with their 
own head and body rather than moving 
the light or lens to observe the entire 
fundus. The image created with this 
method is upside down and backwards, so 
the necessary movements to achieve a view 
of the entire fundus may not be intui  - 
tive. The fundus should be surveyed 
systematically in each quadrant (nasal and 
temporal tapetum and non-  tapetum) and 
the optic disc should be evaluated for 
color, shape, loss of detail or changes in 
depth (e.g. raised or cupped). A raised and 
hyperemic optic disc may indicate optic 
neuritis, while a pale or dark and cupped 
disc may indicate chronic glaucoma. 
Changes in the position or contour of the 
retina, such as in retinal detachment or 
retinal dysplasia should also be noted. 
Subretinal infiltrates, such as inflamma-
tory cells or blood, may be present with 
chorioretinitis.
c. The direct ophthalmoscope can also be 
used to examine the fundus. Although the image acquired is in the correct, upright 
orientation, the fundus is extremely 
magnified and may make interpretation of 
findings more difficult. For the direct 
fundic exam, the examiner’s eye, direct 
ophthalmoscope, and patient’s eye are very 
close to each other (2–3 cm), which may 
be dangerous with unruly patients. The 
direct ophthalmoscope is set to 0 diopters, 
and the examiner moves in closer to the 
patient’s eye until retinal vessels are in 
focus. The same four quadrant survey and 
exam is performed, but this method 
makes the peripheral fundus more 
challenging to see than with the more 
panoramic indirect method.
11. Once the eye exam is completed, all 
abnormalities should be documented, and the 
changes correlated with patient history and 
clinical signs to develop a diagnosis and 
treatment plan. Visual deficits in the absence 
of significant ophthalmic abnormalities may 
be due to conditions such as sudden acquired 
retinal degeneration syndrome (SARDS), 
retrobulbar or optic tract neuropathy or optic 
neuritis, or central vision loss. Consultation 
with a veterinary ophthalmologist and/or 
neurologist may be appropriate depending on 
history and any other clinical signs or 
behavior changes. Additional diagnostic tests 
such as CT or MRI may be indicated with suspicion of orbital disease or central lesions. 
See Table 1 for a selection of abnormal 
findings and possible differential diagnoses.
Although most dogs and cats do not appear 
apprehensive following the use of mydriatic 
drugs, dilation of the pupils can lead to 
photophobia or discomfort in bright light. 
Additionally, some animals are sensitive to 
topical anesthetic drugs, such as propa -
racaine. Effects from these ophthalmic 
drugs can last up to several hours, so clients 
should be made aware of the potential for 
mild blepharospasm or conjunctival 
hyperemia after a complete eye exam.
• STT ≥15 mm/min.
◦ Dogs (normal range 18 ± 3 mm/min).
◦ Cats* (normal range 17 ± 6 mm/min).
*Cats can reportedly have a STT as low as 
0–5 mm/min due to a sympathetic stress 
response.
• IOP 8–20 mmHg in dogs and 10–25 
mmHg in cats.
Table 1
Selection of abnormal findings and potentential differential diagnoses.
Exam component Abnormalities Selection of Possible Diagnoses
Observation Vision deficits Retinal disease, CNS disease (including optic nerve and visual 
tracts), glaucoma, uveitis, cataract, severe keratitis
Palpation Decreased ocular retropulsion ± 
painOrbital disease
Neuro-ophthalmic examination Absent PLR/fixed mydriasis with 
absent menace responseRetinal disease, optic neuritis, glaucoma
Schirmer tear test <10–15 mm/min Keratoconjunctivitis sicca (KCS), dry eye
Fluorescein stain Positive Corneal ulceration
Intraocular pressure >20–25 mmHg (elevated)
<8 mmHg (decreased)Glaucoma (primary or secondary)
Anterior uveitis
Adnexal structures (eyelids, nictitating 
membrane, conjunctiva, nasal lacrimal 
system)Swelling, hyperemia, increased 
ocular discharge
Protrusion of third eyelidBlepharitis, conjunctivitis, Dacryocystitis
Neoplasia
Prolapsed gland of the third eyelid; neoplasiaComplete Ophthalmologic Exam  (continued)

Canine and Feline, Seventh Edition  1511
• STT <10–15 mm/min—likely indicates 
quantitative tear film disorder (KCS).
• IOP >25 mmHg—likely indicates 
glaucoma.
• IOP <8 mmHg—may indicate uveitis.
• Positive fluorescein stain uptake, 
especially in conjunction with clinical signs 
indicating a corneal ulcer.
• Mydriatic drugs, such as topical atropine 
or tropicamide, can suppress the PLR of 
the affected eye(s) and may have long-
lasting effects.
• Some topical glaucoma medications, such 
as latanoprost, can cause extreme miosis, 
precluding the ability to perform a fundic 
exam.
• Systemic anesthetic and sedative agents 
will likely depress the STT results and can 
also blunt the menace response.
• Significant anterior segment changes such 
as marked corneal opacities or cataracts 
may prohibit a posterior segment 
• Patients that are systemically ill or those 
that have neurologic abnormalities  
(e.g., post-ictal changes or CNS disease) may not have a normal menace response or 
neuro-ophthalmic exam.
Procedure Techniques or Handling 
That May Alter Results
Improper restraint during IOP measure -
ments may lead to falsely elevated readings. 
Tight muzzles, or excess pressure on the 
eyelids or neck can lead to increased 
intraocular pressure.
• Chromatic pupillometry.
• Electroretinogram (ERG).
• Gonioscopy.
• Ocular ultrasound.
• Pachymetry.
• Systemic blood pressure.
• Advanced imaging (CT or MRI).
SEE ALSO
• Episcleritis.• Eyelash Disorders.
• Keratitis, Nonulcerative.
• Orbital Diseases.
• Prolapsed Gland of the Third Eyelid.
• Red Eye.
• Uveal Melanoma—Cats.
• Uveal Melanoma—Dogs.
• STT = Schirmer tear test.
Featherstone HJ, Heinrich CL. Ophthalmic 
examination and diagnostics. Part 1: The 
eye examination and diagnostic 
procedures. In: Gelatt KN, Gilger BC, 
5th ed. Hoboken, NJ: Wiley-Blackwell, 
2013, pp. 533–546.
Stades FC, Wyman M, Boeve MH, et al. 
Ophthalmology for the Veterinary 
Practitioner, 2nd ed. Hannover, 
Schlutersche Publishing, 2010, pp. 1–17.
Author  Georgina M. Newbold
Consulting Editor  Benjamin M. Brainard(continued)  Complete Ophthalmologic Exam

1512  Blackwell’s Five-Minute Veterinary Consult  
  BASICS
Blood
• Performed to detect serologic incompati­
bility between a possible blood donor and 
recipient. In contrast with blood typing, 
which recognizes antigens on RBC 
membranes, a crossmatch evaluates plasma 
for the presence of antibodies.
• A major crossmatch, which is of greatest 
clinical significance, tests for alloantibodies in 
patient plasma against donor RBCs. The 
minor crossmatch looks for alloantibodies in 
donor’s plasma against patient’s RBCs. This is 
of lesser concern because the donor’s plasma 
volume is small, particularly in packed RBC 
products, and is markedly diluted in recipients.
• A tube crossmatching procedure is most 
often used, with antibodies indicated by 
subsequent hemolysis or hemagglutination, 
but its interpretation is subjective and 
requires some expertise.
• Gel column technology (DiaMed AG, 
Cressier sur Morat, Switzerland, and Ortho 
Clinical Diagnostic, NJ, USA) is a simple, 
sensitive, and standardized crossmatch 
method, but accessibility is limited. Gel ­based 
and immunochromatographic in ­house 
crossmatching kits are now available for dogs 
and cats, which facilitates the procedure and 
the interpretation of results (DMS 
Laboratories, Flemington, NJ and Alvedia, 
Limonest, France).
Screening blood donors and recipients to 
assure blood compatibility
None
None
None
  SAMPLE
• 1–2 mL of venous blood from donor and 
recipient.
• A segment from the tubing of the donor 
blood bag can be used.
• Collect the patient’s (and possible donor’s) 
blood into EDTA.• Stored donor cells are often in citrated 
phosphate dextrose or citrated phosphate 
dextrose acetate ­1 anticoagulant.
Refrigerate the sample for short ­term storage.
• Whole blood in EDTA—crossmatch within 
48–72 hours of blood collection.
• Properly preserved donor blood—stable for 
4 weeks after collection if stored at 4°C.
PROTOCOL (STANDARD TUBE 
CROSSMATCH)
1. Centrifuge blood (1000 × g for 5 minutes). 
Remove the plasma from each sample with a 
pipette, and transfer the sample to clean, 
labeled tubes. Note any hemolysis.
2. Wash RBCs 3 times with 0.9% saline—
resuspend 0.25 mL of RBCs in 2–4 mL of 
saline. Centrifuge for 1 minute, remove the 
supernatant, repeat the procedure twice, and 
remove the supernatant.
3. Resuspend 0.10–0.25 mL of washed 
RBCs in ≈4.5 mL 0.9% saline to obtain a 
3–5% RBC suspension.
4. For each donor, prepare three tubes 
labeled major, minor, and recipient auto­
control. Add to each tube 2 drops (50  μL) of 
plasma and 1 drop (25 μL) of RBC 
suspension as follows:
a. Major—recipient plasma + donor RBCs.
b. Minor—donor plasma + recipient RBCs.
c. Autocontrol—recipient plasma + 
recipient RBCs.
5. Mix gently and incubate for 15–20 
minutes at 37°C.
6. Centrifuge for 15 seconds.
7. Reading the results—examine the 
supernatant for hemolysis. Gently resuspend 
the RBC button by tapping tube and examine 
for agglutinating clumps. Grade positive 
hemagglutination reactions as 1+ (fine), 2+ 
(small), 3+ (large), or 4+ (1 large agglutinate).
8. If macroscopic agglutination is not 
observed, examine a drop of resuspended 
RBCs for microscopic agglutination (100× or 
400×). This is of questionable importance.
9. A positive reaction in the control tube 
indicates autoantibodies, which complicate 
the interpretation of other tubes.
Compatible crossmatch—the absence of 
hemolysis or hemagglutination.
Incompatible crossmatch—the presence of 
NoneINTERFERING FACTORS
None
Hydroxyethyl starch solution (hetastarch) can 
lead to rouleaux, which can be mistaken for 
agglutination. Rouleaux can be distinguished 
from true agglutination if RBC clusters 
disperse with the addition of saline.
Persistent autoagglutination, such as in 
immune ­mediated hemolytic anemia, 
precludes crossmatching because such samples 
always appear incompatible.
Severe hemolysis may preclude crossmatch 
testing.
Species
• Dogs—first ­time transfusions are 
considered safe without prior crossmatching 
since dogs do not have clinically significant 
naturally ­occurring alloantibodies. Although 
mild immunologic incompatibilities have 
been documented in transfusion ­naive dogs 
(crossmatch weakly incompatible), their 
clinical importance requires further 
• Cats—both AB ­blood typing and cross­
matching are recommended in all cats, even 
with the first transfusion, as 15–19% of cats 
have naturally occurring antibodies against 
RBC antigens outside of the AB system, 
although their clinical importance is unclear.
Breed
• Dogs—previously transfused crossmatch ­
incompatible Dalmatian, Doberman pinschers 
and shih tzu are at great risk of Dal ­
incompatibility (due to an increased frequency 
of Dal ­negative dogs in these breeds).
• Cats—because of the increased prevalence 
of type B cats in certain breeds (e.g., 
Abyssinian, Devon Rex, exotic shorthair), 
A­B incompatibility is more frequently 
encountered in those breeds.
Age
None
Gender
None
Pregnancy
• Dogs—unlike women, bitches do not 
become sensitized to RBC antigens, and 
subsequently produce alloantibodies, during 

Canine and Feline, Seventh Edition  1513
• A compatible crossmatch does not prevent 
sensitization or delayed transfusion reactions. 
It simply indicates that currently there are no 
significant antibodies against the RBCs.
• Crossmatching provides no information 
about leukocyte or platelet compatibility and, 
in some cases, may not be sensitive enough to 
detect anti ­RBC antibodies.
N/A
Yes (excluding direct antiglobulin test).
Any dogs and cats that have been given a 
previous transfusion should be crossmatched 
before they receive additional blood even 
when the same donor is being used. Alloanti­
bodies can develop within 4 days and may 
last for many years.  MISCELLANEOUS
Blood typing.
SYNONYMS
None
SEE ALSO
Blood Typing (in Appendix X).
Blais MC, Rozanski EA, Hale AS, et al. Lack 
of evidence of pregnancy ­induced alloanti­
bodies in dogs. J Vet Intern Med 2009, 
23:462–465.
Giger U, Gelens CJ, Callan MB, et al. An 
acute hemolytic transfusion reaction caused 
by dog erythrocyte antigen 1.1 incompat­
ibility in a previously sensitized dog. J Am 
Vet Med Assoc. 1995, 206:1358–1362.
Goulet S, Blais MC. Characterization of 
anti­Dal alloantibodies following sensitiza­tion of two Dal ­negative dogs. Vet Pathol 
2018, 55:108–115.
McClosky ME, Cimino Brown D, Weinstein 
NM, et al. Prevalence of naturally occurring 
non­AB blood type incompatibilities in cats 
and influence of crossmatch on transfusion 
outcomes. J Vet Intern Med 2018, 
32:1934–1942.
Sylvane B, Prittie J, Hohenhaus AE, et al. 
Effect of cross ­match on packed cell volume 
after transfusion of packed red blood cells in 
transfusion ­naïve anemic cats. J Vet Intern 
Med 2018, 32:1077–1083
shorthair cats: The Mik red cell antigen. J 
Author  Marie ­Claude Blais
Consulting Editor  Benjamin M. Brainard(continued)  Crossmatch

1514  Blackwell’s Five-Minute Veterinary Consult  
Cystocentesis
  BASICS
• Cystocentesis is the gold standard for sterile 
collection of urine for urinalysis and urine culture.
• Urinalysis is part of the minimum database 
when evaluating ill dogs and cats or when 
performing routine health screens. Urine culture 
should be performed in animals with clinical 
signs of lower urinary tract disease (e.g., 
pollakiuria, dysuria), in animals with active urine 
sediment, in animals with acute kidney injury, 
and in animals with diseases known to predispose 
them to urinary tract infections (e.g., diabetes 
mellitus, hyperadrenocorticism, renal failure).
• Routine collection of urine samples for 
urinalysis or urine culture.
• Immediate relief of bladder overdistention, 
and to facilitate bladder catheterization, in 
animals with urethral obstruction.
• Pregnancy or pyometra.
• Suspected or confirmed transitional cell 
• Severe and diffuse cutaneous disease of 
caudal abdomen (e.g., severe pyoderma, 
pemphigus complex).
• Insufficient volume of urine within the 
bladder.
• Seeding of transitional cell carcinoma 
tumor cells into the abdomen or along the 
needle track.
• T ransient hematuria (rare).
• Iatrogenic urinary tract infection (very rare).
• Bladder rupture (very rare).
• Aortic laceration (very rare).
• Vasovagal response (very rare).
None
  PROCEDURE
• Typically, none is required. Uncooperative 
patients may require slight sedation for the 
procedure.• In rare cases, where urine is required for 
urinalysis or culture, but frequent voiding or 
recent urination has hampered urine 
collection, a single dose of isotonic fluids can 
be administered, although this will affect 
urine specific gravity.
None is needed in most patients. 
Uncooperative patients may require slight 
sedation for the procedure. Alpha-2 agonists 
will increase urine flow and decrease urine 
• For cystocentesis, the bladder is best 
palpated and isolated while the patient is in 
lateral recumbency (dogs and cats) or 
standing (dogs).
• Blind cystocentesis is performed with the 
patient in dorsal recumbency.
None
• A 3- to 12-mL syringe.
• A 22-gauge needle (usually 1–1½ inches).
• 70% alcohol (ethyl or isopropyl) for skin 
preparation.
TECHNIQUE
• The bladder should be palpated prior to 
attempting cystocentesis. The bladder is 
normally present in the caudal abdomen; 
with increased urine volumes the bladder will 
move cranially, toward the ventral body wall.
• If the bladder can be palpated and contains 
enough urine to attempt cystocentesis, the 
bladder isolation technique should be used. 
In those dogs where the bladder is not easily 
palpated, ultrasound guidance or a blind 
aspiration technique can be attempted. Blind 
aspiration is more commonly associated with 
complications and is less likely to be 
• Attach the needle to the syringe.
Bladder Isolation Technique
• Restrain the patient in lateral recumbency. 
In some dogs, the bladder is more easily 
palpated with the patient standing.
• The individual palpating the bladder 
should isolate the bladder with one hand.
• Clean or spray the cystocentesis site with 
70% alcohol.
• Keeping the bladder isolated, the needle 
should be inserted into the bladder without 
applying negative pressure.
• Alternatively, an assistant can attempt 
cystocentesis by inserting the needle and 
syringe between the fingers of the person who 
has isolated the bladder. This allows the 
bladder to be isolated by using two hands and 
may be easier in dogs. The individual 
palpating the bladder should guide the 
assistant as to how far to insert the needle.• Once the needle has been inserted to the 
appropriate depth, the syringe plunger should 
be slowly drawn back, creating negative 
pressure. Negative pressure should not be 
applied until the person performing the 
procedure believes the bladder has been 
entered.
• When the desired volume of urine has been 
collected, negative pressure should be released 
and the syringe and needle removed.
Ultrasound Guidance Technique
• Restrain the patient in dorsal recumbency 
and using ultrasound identify the bladder on 
ventral midline of the caudal abdomen.
• Insert the needle at an oblique angle to the 
probe where the bladder is visualized.
• When the needle is seen entering the 
bladder lumen, the syringe plunger should be 
slowly drawn back, creating negative pressure.
Blind Aspiration Technique
with the rear limbs extended.
• Spray 70% alcohol over the caudal ventral 
abdomen.
• The needle is inserted on midline at the site 
where alcohol pools. Alternatively, the bladder 
position can be estimated by determining where 
lines drawn between the last two sets of nipples 
theoretically cross (Figure 1). In male dogs, 
move the prepuce and penis to the side to 
enable insertion of the needle and syringe on the 
midline plane. The needle should be directed 
caudally at an approximately 30–45° angle.
• Once the needle has been inserted to the 
appropriate depth, the plunger of the syringe 
should be slowly drawn back, creating 
negative pressure. If urine is not obtained, 
remove the needle and re-attempt at a site just 
cranial or caudal.
• If GI tract content or blood is seen in the 
needle hub, release the negative pressure and 
then withdraw the needle and syringe. A fresh 
needle and syringe should be used if blind 
cystocentesis is reattempted.
and the syringe and needle withdrawn.
Decompressive Cystocentesis 
for Animals with Urethral Obstruction
• Serially attach the needle to IV extension 
tubing, a three-way stopcock, and a 20- to 
60-mL syringe.
• Restrain the patient in dorsal or lateral 
recumbency and identify the bladder via 
palpation or with ultrasound.

Canine and Feline, Seventh Edition  1515
• Insert the needle into the bladder at a 45° 
angle.
should be slowly drawn back, creating negative 
pressure. If urine is obtained, continue aspiration 
to remove the maximal volume of urine possible.
• When the maximal volume of urine has 
been collected, negative pressure should be 
released and the needle withdrawn.
• Samples collected for urinalysis should be 
analyzed immediately, if possible, because 
refrigeration for later analysis can alter some 
dipstick and sediment findings.
• Urine samples collected for culture should 
be refrigerated or placed into bacteriostatic 
transport containers until plated onto 
appropriate media. The amount of urine to 
be submitted varies among diagnostic 
laboratories, but many microbiologists prefer 
at least 5 mL because this may increase the 
likelihood of isolation of infectious agents.
None
None
None
None
NoneAnticipated Recovery Time
Immediate
N/A
N/A
N/A
• A number of drugs affect urinalysis 
findings. A thorough medical history is 
required for proper interpretation of results.
• Antibiotics may inhibit growth of bacteria 
if urine is submitted for culture.
• Cystocentesis may be difficult at times of 
low bladder urine volume (e.g., immediately 
after voiding; in pollakiuric patients). Urinary 
catheterization using sterile technique will 
allow small amounts of urine to be collected.
• Bladder rupture.
• Improper or delayed handling of urine after 
collection affects urinalysis results.• Urine samples may be contaminated 
inadvertently with GI tract content if 
aspiration is performed prior to the needle 
entering the bladder. Partially digested food, 
feces, and bacteria cause a false-positive active 
urine sediment and positive urine culture.
Species
See Urinalysis Overview (Appendix X) for 
details regarding interpretation in dogs and 
cats. Some differences of note include these:
• Cat urine is typically more concentrated 
than dog urine, although the reference ranges 
in normal animals overlap significantly.
• Dogs may normally have a small amount of 
bilirubinuria, whereas bilirubinuria in cats is 
always a pathologic finding.
• Cats typically have more acidic urine than 
dogs; however, urine pH is significantly 
influenced by diet.
• Fat droplets are common in feline urine but 
rare in canine urine.
Breed
None
Age
• Neonatal puppies (<3 weeks old) have more 
dilute urine than pediatric or adult dogs.
• T ransient proteinuria and glucosuria have 
been reported in neonatal puppies, although 
this is not a consistent finding in all studies.
Gender
Male dogs may have higher concentrations of 
urine bilirubin than female dogs.
Figure 1 .
A female dog in dorsal recumbency, with dotted lines drawn between the last two sets of nipples. In 
the blind aspiration cystocentesis technique, the needle should be inserted where the lines cross and 
the needle directed caudally at an approximately 30–45° angle. Source: Lawrence P . Tilley(continued)  Cystocentesis

1516  Blackwell’s Five-Minute Veterinary Consult  
Pregnancy
None
Cystocentesis should be considered the 
standard method for urine collection in all 
small-animal patients:
• Urine samples collected by catheterization 
or midstream free catch may be contaminated 
by microorganisms and inflammatory cells 
normally found in the distal urethra, prepuce, 
and vaginal vault. Results of urine sediment 
examination or culture from urine samples 
not collected by cystocentesis must be 
interpreted with caution, and there is a higher 
risk of artifactual bacterial contamination.
• Comparison of urinalysis findings from 
cystocentesis and free-catch midstream urine 
samples may assist in differentiating urethral or genital disease from bladder or upper 
• Although cystocentesis of animals that may 
have transitional cell carcinoma of the urinary 
bladder may seed tumor cells into the abdomen 
or along the needle track, cystocentesis should 
still be routinely performed in dogs and cats 
unless a bladder mass has been confirmed by 
diagnostic imaging studies.
• Urethral catheterization.
• Urinalysis.
• Urine culture.SYNONYMS
Bladder tap
SEE ALSO
• Bacterial Culture and Sensitivity (in 
• Urethral Catheterization (in Appendix X).
• Urinalysis Overview (in Appendix X).
• Urine Sediment (in Appendix X).
Author  Vincent J. Thawley
M. Pressler.Cystocentesis  (continued)

Canine and Feline, Seventh Edition  1517
  BASICS
Electrodiagnostic: heart electrical activity 
measurement
• The electrocardiogram (ECG, EKG; 
Figure 1) captures the electrical fields 
generated by the pumping heart. Waveforms 
are a display of the electrical activity of the 
heart generated during depolarization and 
repolarization.
• The leads represent single planes of 
measurement of the electrical activity of the 
heart. Each lead has a positive and negative 
surface electrode setting. If energy is traveling 
away from the positive electrode, a negative 
orientation of the wave occurs on the ECG, 
and if the net direction of the electrical energy 
impulse is toward the positive electrode, a 
positive deflection occurs. If the impulses are 
at perpendicular, an isoelectric deflection 
occurs. Lead II is the most common lead used 
for initial evaluation of the ECG.
• The form of the ECG is characterized by 
deviations from baseline that are linked to 
specific events in the cardiac cycle (Figure 1):
◦ Each cardiac cycle starts with an impulse 
that originates in the sinoatrial (SA) node, 
which is located in the right atrium. An 
impulse will travel through the myocardium 
of the atria, resulting in depolarization. This event generates the P wave on the tracing. 
The tracing is recorded when the atrium 
contracts, not when the original SA node 
fires, because the latter event is too small to 
trigger a recordable event.
◦ As the impulse moves through the 
atrioventricular (AV) node, which is near 
the base of the right atrium, the PR interval 
is generated.
◦ Once through the AV node, the 
conduction speed increases and the 
electrical activity fires through the bundle 
of His, the bundle branches, and the 
Purkinje system.
◦ Rapid, widespread depolarization of the 
ventricles then occurs. This leads to the 
QRS complex. Subsequent ventricle 
contraction then occurs.
◦ The Q wave represents the interventricu-
lar septum depolarization and thus is the 
first negative deflection. The Q wave may 
not always be easy to isolate on tracings.
◦ The R portion is the ventricular 
myocardium depolarizing and the impulse 
traveling from the endocardium to the 
epicardium. It is a positive deflection and 
the most prominent waveform on the ECG.
◦ The S wave is the basal ventricle posterior 
wall and interventricular septum activating. 
It is the first negative deflection following 
the R wave.
◦ The repolarization of the ventricles is 
recorded as the T wave.
◦ As repolarization occurs, the ST segment 
is generated.INDICATIONS
• Diagnosis of cardiac arrhythmias, myocar-
dial ischemia, changes in cardiac environment 
(e.g., pericardial effusion, pericarditis).
• Patients with the following clinical signs:
◦ Tachycardia or bradycardia.
◦ Dyspnea, cyanosis, syncope, or seizures.
◦ Shock, acute emergency, or severe illness, 
such as pyometra, gastric dilatation and 
volvulus syndrome (GDV or bloat), uremia, 
pancreatitis, and toxic insults.
◦ Electrolyte disturbances (especially 
potassium) or in chronic diuretic 
◦ Cardiac murmurs.
• Also used in the context of patient 
monitoring:
◦ During anesthesia and in the periopera-
tive period.
◦ Routine health monitoring of senior or 
chronically ill patients where prognosis may 
be affected by cardiac function.
◦ Pharmacologic monitoring for agents 
with known cardiotoxicity (e.g., quinidine, 
digitalis, beta-blockers).
• In patients with an abnormal radiographic 
appearance of the heart or great vessels, in 
combination with other diagnostics (e.g., 
• During diagnostic or therapeutic proce-
dures, (e.g., pericardiocentesis).
• In patients with elevations in vagal tone 
(e.g., disease in the nervous system, respira-
tory system, GI system, use of potent 
opioids).
Normal sinu s
rhythm
Sinus
tachycardia
Sinus
brady cardia
Sinus
arrhythmia
Figure 1 .
Common examples of electrocardiograms.

1518  Blackwell’s Five-Minute Veterinary Consult  
None
Caution in dyspneic patients.
• Inform clients that this is not a standalone 
test but interpreted in the context of the 
patient’s medical history, clinical signs, and 
other database findings.
• Let them know that this is just a snapshot 
and that repeat ECG and Holter monitoring 
may be required to understand the problem 
more fully, especially with paroxysmal 
tachycardias and with conduction distur-
bances (e.g., AV block).
  PROCEDURE
• The number of leads measured depends on 
the equipment.
• Three bipolar leads is minimum, and three 
additional unipolar leads are usual.
• This type of procedure does require a quiet, 
calm environment (and animal) in order to 
optimize results. Distraction during the test 
may produce spurious results, so care should 
be taken to let the animal settle in before 
measurement begins.
• An experienced technician or veterinarian 
should run the test and, ideally, serial tests 
should be conducted and interpreted by the 
same individuals to help maintain 
consistency.
• T urn off fluorescent bulbs or electrical 
equipment (especially in older equipment) in 
the room, do not cross your limbs, and avoid 
contact with metal surfaces.
• Before recording begins, clips must be 
effectively placed. The right arm (RA) and 
left arm (LA) electrodes are best clipped to 
the proximal olecranon area or even halfway 
down the radius. The right leg (RL) and left 
leg (LL) electrodes are clipped over the patella 
ligament. Before applying a clip, remember to 
apply conductive gel or 70% isopropyl 
alcohol. The advantage of the latter is that it 
does not get gummed up in long hair. For 
longer term (e.g., intraoperative) monitoring, 
gel is better because alcohol evaporates too 
quickly. The precordial chest (V lead) 
electrode is applied for precordial unipolar 
chest leads.
• Muscle tremors may produce artifacts. 
Movements and purring can lead to 
vibrations along the baseline. A hand placed gently on the animal’s chest wall may help to 
reduce its shivering.
• A wandering baseline is often caused by 
respiratory cycle movements because contact 
at the skin–clip interface can be poor. Panting 
or coughing may also cause the same thing. 
To resolve this issue, gently hold the muzzle 
closed for 4 seconds, as long as the patient is 
not dyspneic.
• Anesthesia is not required, and sedation is 
rarely required.
• Pediatric patients may require snug restraint 
to enable testing.
• Since reference levels originate from the 
right lateral recumbent position, that position 
would be ideal, but, realistically, if a pet is 
recalcitrant or dyspneic, any position that 
minimizes tremors, shivering, panting, or 
struggling will do. As an alternative, standing 
is preferred to sitting if right lateral recum-
bency is too stressful.
• Ideally, the forelimbs would be held apart 
and perpendicular to minimize interference, 
in amenable patients.
• If indicated, oxygen delivered by mask or 
flow-by techniques may be provided during 
the exam.
• For intraoperative monitoring, a patient’s 
position is not critical.
Monitor for sudden dyspnea or cyanosis or 
other signs that reflect decompensation.
• ECG equipment is relatively inexpensive 
and ranges from transtelephonic sets to 
integrated computer oscillometric recorders 
that can print and upload to the computer-
ized patient record directly.
• A blanket or soft pad for the table.
• An ECG recording machine. The ECG 
apparatus should meet the requirements of 
the Committee on Electrocardiography of the 
American Heart Association. The amplifier is 
tied to a strip recorder, either on a computer 
screen or an oscilloscope, or by a stylus on 
wax paper. At a minimum, single-channel 
capture and an oscilloscope should be 
available. Three-channel equipment enables 
more detailed capture and analysis by 
enabling the tester to record three leads 
• Contact gel or 70% isopropyl alcohol.
• Clippers if the hair is too thick to provide 
close clip contact.
• A printer or a computer or transtelephony 
device, depending on where the results are to 
be sent or how they are to be recorded.
• Separate the cables so they do not overlap. 
Usually, this is a set of five wires. Alligator 
clips are usually used for animals. Plate clips are better for electrical sensitivity but are 
more easily displaced by struggling animals:
◦ The alligator clips, which should be 
copper, may be filed and bent so they pinch 
less. With very small animals, placing a 
plate inside the clip may help maintain the 
patient’s comfort without loss of efficiency.
◦ Alternatively, adhesive pads for human 
use may be applied to the patient for longer 
term ECG recording. Special clips may be 
used to attach to the button on the pad, or 
regular clips may be attached as well.
TECHNIQUE
• Run the standardization marker for 
sensitivity and increase speed to 50 mm/s 
before you start to record. If only using the 
ECG for periprocedural or in hospital 
monitoring, a speed of 25 mm/s is adequate 
unless the patient is very tachycardic.
• Switch leads to obtain 4-second segments 
approximately, with the goal to record a 
minimum of four good complexes in each 
lead to fully assess the electrical activity. 
Repeat as needed to cover available leads for 
the system.
• Finally, record a long strip of lead II for full 
rhythm assessment.
• A break will be needed if precordial leads 
are to be recorded, because the electrodes will 
need to be repositioned. T urn off the 
machine, turn it back on, and run the 
standardization again before recording.
• T urn off the record switch, turn off the 
machine, and clean the gel from the hair coat 
after gently removing the clips.
• For transtelephonic ECG, the portable 
preamplifier converts electrical signals into 
tones that can be sent over a phone line. 
Position the animal, attach two electrodes 
(moistened for good contact) to the forelimbs 
near the elbow, and then call the transtel-
ephonic service.
• Sensitivity controls how tall the complexes 
are, with 1 mV being standard. This means 
10 small boxes (1 cm) equals 1 mV.
• Change to 2 mV to increase the size of the 
complexes represented and to 0.5 mV to 
reduce the height of tall complexes.
• A marker must be done at the start of each 
strip to record the lead sensitivity. Newer 
models do this automatically.
• Position the baseline recording in the center 
of the paper strip for recording.
• Record at least 5–6 complexes for each lead 
and record a long strip especially if watching 
for arrhythmias. Check the polarity: If the R 
waves are not positive in lead I, check the 
hookup to see if it is still negative, which is 
abnormal for lead I.
• Placement of the grounding is not 
critical except that it should be far away as 
possible.Electrocardiography  (continued)

Canine and Feline, Seventh Edition  1519
• If using a rhythm strip to monitor ECG 
during procedures, the specific lead is 
unimportant, as long as the observer can 
identify a P , QRS, and T complex in the 
tracing (i.e., lead II may be isoelectric 
following positioning for a surgery such as a 
forelimb amputation, but lead III may be 
adequate for rhythm monitoring).
The findings can be divided into heart rate 
(HR), rhythm, analysis of complexes and 
intervals, electrical axis, and chest leads. (See 
an ECG text guide for interpretation details.) 
Abnormalities in rhythm, complexes and 
intervals, and waveforms, and disturbances in 
impulse conduction and mean electrical axis 
(MEA) can occur. Normal values for ECG 
analysis are listed in Appendix IV. An 
extensive review of ECG interpretation is 
beyond the scope of this chapter (see 
Suggested Reading), but some general tips to 
interpret ECG follow.
Heart Rate
• When ECG is run at 25 mm/s, each large 
box on the paper is equal to 1/5 of a second, 
and each set of five large boxes (usually 
indicated by a black mark at the base of the 
grid) is equivalent to 1 second of ECG.
• The rate is calculated by observing the 
number of QRS complexes in a 3-second 
interval.
• Multipy this number by 20 to calculate the 
beats per minute.
• At 50 mm/s, three sets of large boxes is 
equivalent to 1.5 seconds and the number of 
QRS complexes should be multiplied by 40.
Arrhythmia Analysis
See specific arrhythmia chapters for visual 
examples and therapeutic recommendations.
• First, calculate the rate.
• Note the regularity of the QRS complexes 
and characterize the rhythm as regular or 
irregular:
◦ Patients that have rhythmic variation due 
to breathing have a regularly irregular 
rhythm (i.e, irregular in a predictable way).
◦ Animals with atrial fibrillation have an 
irregularly irregular rhythm, without any 
discernible pattern.
• Evaluate the tracing for P waves. A P wave 
should precede every QRS complex:
◦ Evaluate the distance between the P wave 
and each QRS (should be the same).
◦ Patients with various AV blocks may not 
have a reliable P-R interval or P waves in general. Patients with ventricular or 
junctional arrhythmias will have QRS 
complexes without associated P waves.
• Verify that there is a QRS complex for 
every identified P wave. QRS complexes 
without P waves may originate from the 
ventricles or AV junction.
Related to specific arrhythmias; diagnosis of 
ventricular tachycardia, ventricular 
fibrillation, third-degree AV block, sinus 
arrest (lack of P waves), and asystole require 
immediate intervention and further 
diagnostic testing.
• Environmental interference, interpretation 
error, interpretation without a proper 
minimum database, or overinterpretation.
• The ECG does not assess the heart itself, 
just the electrical activity of the myocardium, 
so an animal with advanced congestive heart 
failure (CHF) may have a normal ECG, and 
an animal with cardiac arrest may display 
normal activity for a period of time after the 
heart stops beating (the electrical activity is 
just not translated into muscular contraction).
• Since not all abnormalities are present all of 
the time, serial studies or Holter monitors 
• Breed and conformation may affect the 
tracings and interpretation.
Sedation (e.g., with alpha-2 agonist drugs) 
may cause artifactual arrhythmias, or mask 
the presence of others.
Electrical interference, stress, dyspnea, or an 
uncooperative patient.
A wandering baseline caused by movement, 
not adjusting the millivoltage or speed, 
improper patient position, contact with a 
metal surface, crossed wires or legs, or 
electrical interference.
Species
Interpretations of tracings are specific to 
species.
Breed
Clip placement is affected in deep-chested 
breeds.Age
Young dogs.
Gender
None
Pregnancy
None
The ECG may be used for simple rhythm 
monitoring, or may provide specific insight 
into cardiac disease. A thorough understanding 
of the technique and the causes of the 
deflections on the final waveforms will 
completment other diagnostic results. 
Knowing your equipment, taking care to 
minimize stress, and developing a proper 
database of information against which to 
compare results before making an 
interpretation are important.
• Holter monitoring.
• Radiography.
• Ultrasound, echocardiogram.
• Pericardiocentesis.
SYNONYMS
None
SEE ALSO
Cardiology topics, specific arrhythmias.
• ECG, EKG = electrocardiogram.
• MEA = mean electrical axis.
•  Suggested Reading
Smith FWK, Tilley LP , Miller MS. 
Electrocardiography. In: Brichard SJ, 
Sherding RG, eds., Manual of Small Animal 
Practice, 3rd ed. St. Louis, MO: Saunders 
Elsevier, 2006.
Electrocardiography. Interpretation and 
T reatment, 3rd ed. Ames, IA: Blackwell, 1992.
Tilley LP , Burtnick N. ECG for the Small 
Animal Practitioner. Jackson, WY: Teton 
NewMedia, 1999.
Consulting Editor  Benjamin M. Brainard(continued)  Electrocardiography

1520  Blackwell’s Five-Minute Veterinary Consult  
Fecal Direct Smear and Cytology
  BASICS
Feces
• Performed to examine the fecal microbiota 
and any nucleated cells that are present 
(epithelial, inflammatory), and to detect other 
pathogens that may be present (i.e., bacterial, 
fungal, protozoal, algal, oomycetal).
• Abnormalities detected by fecal cytology are 
often nonspecific, and may enable diagnosis 
of the primary cause of GI illness in some 
cases, although may more frequently 
represent findings associated with other 
underlying diseases or processes.
• Direct fecal smear cytology is not 
synonymous with a rectal scrape, which is a 
method of sampling the rectal mucosa by 
direct scraping of its surface with a swab or 
blunt spatula. Rectal scraping is typically 
required to identify some deeper infections 
(e.g., histoplasmosis, protothecosis).
• Less commonly, other GI signs (e.g., vomition).
None
None
• This test may not reveal the primary cause of 
a patient’s GI signs. Instead, abnormalities 
secondary to other underlying primary or 
secondary GI disease may be detected.
• Normal direct fecal smear cytology does not 
definitively exclude the possibility of GI disease, 
including underlying infection or inflammation.
  SAMPLE
Collect feces from the rectum by using a 
slightly moistened cotton-tipped applicator or 
use the feces present on one’s gloved finger 
after a digital rectal exam.
• Smear or roll the feces onto a clean, glass 
microscope slide to form a thin film.
• Prepare a wet preparation by adding a few 
drops of saline and a coverslip. Do not make 
the wet preparation too thick; one should be 
able read newsprint through the wet prep. 
Adding a drop of iodine to the preparation 
may improve visualization of protozoa.• Air-dry the thin film of feces:
◦ Stain with a Romanowsky stain (e.g., 
Diff-Quik; Dade Behring, Newark, DE) for 
◦ Use acid-fast stain if looking for 
Cryptosporidium  sp.
◦ Heat-fix prior to Gram staining.
• Wet preparations should be prepared and 
immediately examined.
• For other preparations, the sample should 
be processed within 2 hours or feces should 
be refrigerated.
• Store air-dried fecal smears at room 
temperature and protected from light.
• Fecal smear slides should not be refrigerated 
or frozen.
• Wet preparations should be read immed -
iately and cannot be stored.
• Feces at room temperature: 2 hours.
• Refrigerated feces: variable stability, 
depending on abnormality of interest. Parasite 
ova are stable, but cellular deterioration and 
changes in bacteria flora occur over time.
• Wet preparations cannot be stored.
• Fixed-stain smears are stable indefinitely if 
protected from light and humidity.
PROTOCOL
• Examine the wet preparation for motile 
parasites or parasite ova.
• Examine the Romanovsky-stained smear for 
◦ Background bacterial flora.
◦ Noninflammatory cells (e.g., epithelial 
cells, neoplastic cells).
◦ Inflammatory cells.
◦ The number of spore-forming bacteria per 
1,000× high-power field.
◦ The presence of pathogens, such as the 
following (depending on geographic location):
◾ Short spiral or gullwing-shaped bacteria 
(e.g., Campylobacter , Helicobacter , 
Anaerobiospirillum , treponeme-like 
bacteria, Serpulina  spp.)
◾ Protozoa (e.g., Giardia , Tritrichomonas , 
Entamoeba ).
◾ Dimorphic fungi (e.g., Histoplasma ).
◾ Other fungi (e.g., Cryptococcus , Candida , 
Aspergillus ).
◾ Algae (e.g., Prototheca ).
◾ Oomycetes (e.g., Pythium ).
• A polymorphic bacterial population of 
bacilli. Cocci should be absent or very rarely 
observed.
• A low number of well-differentiated 
• Amorphous material, representing digesta.• A small amount of plant material.
• A small amount of extracellular yeast (e.g., 
Cyniclomyces ; formerly known as 
Saccharomycopsis ).
• Monomorphic bacterial microbiota.
• An increased number of cocci.
• The presence of inflammatory cells.
• The presence of abnormal noninflammatory 
cells (e.g., reactive epithelial cells, neoplastic 
cells).
• The presence of potential pathogens (e.g., 
protozoa, fungi, algae, oomycetes, gullwing-
shaped bacteria).
• The presence of >10 spore-forming bacteria 
per 1,000× high-power field.
• Specifically, sporulated Clostridium  has a 
safety-pin or tennis racket appearance because 
the spore produces an oval, colorless area.
None
None
Prior antimicrobial administration may alter 
the GI microbiota, resulting in abnormal 
direct fecal smear cytologic results.
Prior GI procedures (e.g., surgery, enema) 
may alter GI flora, resulting in abnormal 
Collection Techniques or Handling that 
Deeper scraping of the rectal mucosa will 
increase the number of epithelial cells 
observed in direct fecal smear cytology. 
Deeper scraping may be helpful when certain 
infections (e.g., histoplasmosis, protothecosis) 
are suspected.
Species
None
Breed
None
Age
None
Gender
None
Pregnancy
None
None

Canine and Feline, Seventh Edition  1521
Yes, if the observer (i.e., pathologist or 
technician) is acquainted with veterinary species.
• Abnormal background bacterial microbiota 
is often an incidental finding associated with 
other primary or secondary GI diseases, with 
GI procedures, or with prior antimicrobial 
administration. In some cases, though, 
abnormal microbiota may be a factor 
contributing to diarrhea.
• Observation of inflammatory cells suggests 
the presence of transmural colonic or rectal 
inflammation. Fecal culture may be useful to 
exclude underlying infection by invasive 
bacteria (e.g., salmonellosis).
• Identification of atypical noninflammatory 
cells, such as abnormal epithelial cells, may 
indicate the presence of neoplasia or 
• The primary cause of diarrhea may be 
determined when pathogens (e.g., bacterial, 
protozoal, fungal, algal, oomycetal) or an 
increased number of spore-forming bacteria 
are observed.  MISCELLANEOUS
• Fecal culture and determination of antibiotic 
sensitivities are useful when inflammatory cells 
or pathogens are observed.
• Gram stain of the direct fecal smear is useful 
in evaluating the microbiota and potential 
bacterial pathogens.
• Warthin–Starry silver stain of the direct fecal 
smear is useful in evaluating potential bacterial 
pathogens (e.g., Lawsonia ).
• Submission of direct fecal smear to a 
referral laboratory for cytologic evaluation is 
useful when abnormal noninflammatory cells 
(e.g., atypical epithelial cells) or when 
potential pathogens are observed.
• Other tests employed as part of routine GI 
diagnostic evaluation may include serum 
biochemistry, fecal flotation, fecal pathogen 
PCR, and radiography.
SYNONYMS
Fecal cytology
SEE ALSO
• Acute Diarrhea.• Diarrhea, Chronic—Cats.
• Fecal Flotation (in Appendix X).
Andreason CB, Jergens AE, Meyer DJ. Oral 
cavity, gastrointestinal tract, and associated 
structures. In: Raskin RE, Meyer DJ, eds. 
Atlas of Canine and Feline Cytology. 
Philadelphia, PA: WB Saunders, 2001, 
pp. 207–229.
Broussard J. Optimal fecal assessment. Clin 
Tech Small Anim Pract 2003; 18:218–230.
Lassen ED. Laboratory evaluation of 
digestion and intestinal absorption. In: 
Thrall MA, ed., Veterinary Hematology and 
Clinical Chemistry. Philadelphia, PA: 
Lippincott Williams & Wilkins, 2004, 
pp. 387–399.
Authors  Andrew R. Moorhead and 
Guilherme G. Verocai
Heather L. Wamsley.Table 1
Preparation Abnormal Finding Possible Causes
Wet preparation Motile protozoa Giardia, Balantidium, Entamoeba, Tritrichomonas  trophozoites
Parasite larvae Strongyloides, Aelurostrongylus, Filaroides , saprophytic larvae 
caused by environmental contamination
Parasite eggs Coccidia ( Cystoisospora  spp.), Toxocara, Trichuris, Ancylostoma, 
Uncinaria
Romanowsky stain Monomorphic population of bacteria Bacterial overgrowth caused by primary or secondary GI 
disease or antibiotic treatment
Sporulated bacteria Clostridium  overgrowth
Short spiral or gullwing-shaped bacteria Campylobacter, Helicobacter, Anaerobiospirillum
White (colorless) rods in macrophages and free in background Mycobacterium
Neutrophils Nonspecific sign of GI inflammation or suggests the presence 
of transmural colonic or rectal inflammation
Eosinophils Allergic hypersensitivity or parasitic infection
Small lymphocytes, plasma cells Lymphocytic, plasmacytic enteritis
Monomorphic large lymphocytes Lymphoma
Teardrop-shaped protozoan organisms with 2 nuclei that 
“appear to be looking back at you”Giardia
Spindle-shaped protozoa with whiplike flagella and an 
undulating or wavy membraneTritrichomonas
Ciliated protozoan with a large sausage-shaped macronucleus 
that surrounds a small micronucleusBalantidium
Round intracellular yeast (within macrophages), 3–5 μm 
diameterHistoplasma
Septate branching hyphae Aspergillus , other fungus, or Pythium
Round or oval algae with basophilic granular cytoplasm (3 × 
16 μm)Prototheca
Acid-fast stain 4–5 μm round magenta structures Cryptosporidia  sp.
Intracellular magenta linear inclusions Mycobacterium(continued)  Fecal Direct Smear and Cytology

1522  Blackwell’s Five-Minute Veterinary Consult  
Fecal Flotation
  BASICS
Feces
• Designed to recover diagnostic stages of 
parasites that are shed in feces (e.g., eggs, 
oocysts, and cysts).
• Based on specific gravity (SG) of flotation 
solution.
• Parasite eggs, oocysts, and cysts will float in 
solutions of a higher SG than the parasitic life 
stage. The SG of most parasite eggs is 
between 1.05 and 1.23. Therefore, for 
parasite eggs to float, the SG of the flotation 
solution must be greater than that of the eggs.
• Flotation solutions are made by adding a 
measured amount of salt or sugar to water to 
produce a solution with the desired SG. 
Solutions may be made from scratch or 
bought premixed.
• Common flotation solutions include sugar 
(Sheather’s solution; SG, 1.2–1.33), sodium 
nitrate (NaNO3; SG, 1.2–1.3), and zinc 
sulfate (ZnSO4; SG, 1.18–1.2).
• Most parasitology diagnostic and research 
laboratories routinely use Sheather’s solution, 
which will float most common parasite eggs.
• Many commercially available kits supply 
sodium nitrate.
• Zinc sulfate is considered the gold standard 
for flotation of Giardia  cysts.
• Sodium nitrate solution is widely used for fecal 
egg counts of large and production animals, and 
might an option for mixed practices.
• The SG of a flotation solution should be 
verified with a hydrometer and then checked 
on a routine basis (e.g., monthly) to detect 
SG changes caused by evaporation. If the SG 
is too high, it may rupture eggs, oocysts, or 
cysts.
• Routine health screening.
• Digestive upsets; vomiting and/or diarrhea.
• Respiratory signs such as chronic coughing 
or sneezing.
None, other than insufficient fecal output.
None
• Because pets can have normal stools and 
still be infected with intestinal parasites, it is 
good medicine to perform routine fecal exams 
on all pets. The absence of diarrhea or visible 
worms in dog feces does not mean that the 
animal is not infected.• Negative fecal flotation does not completely 
exclude the possibility of gastrointestinal or 
respiratory parasites. For example, tapeworm 
segments (or proglottids) may be seen in the 
feces, and the flotation may be negative for 
several reasons: eggs were not released from 
the segment, the SG of the solution used was 
not high enough to float the heavy taeniid-
type eggs (i.e., T aenia  and Echinocccus ), or 
perhaps owners mistook grains of rice or fly 
larvae for tapeworm segments.
• All dogs and cats should receive regular 
heartworm preventives based on macrocyclic 
lactone drugs; however, these products may 
not treat or prevent infection by some 
intestinal worms or other parasites such as 
tapeworms, flukes, Coccidia , or Giardia .
  SAMPLE
Minimum of 1 g, ideally 2–3 g of fresh feces.
• Place the sample in an airtight container 
(e.g., screw-top jar, ziplock bag).
• Every sample must be appropriately labeled.
• The sample is best analyzed on the day of 
• If not possible, keep it cooled or refrigerated 
until processing, avoid freezing.
Refrigeration
The stability of organisms and life stages 
varies; e.g., Giardia  cysts are very fragile and 
delicate, whereas ascarid eggs are very hardy.
EQUIPMENT
• Scale able to weigh up to 5 g.
• Light microscope with objectives of 10× 
and 40× magnification.
• Benchtop centrifuge (swinging-bucket or 
fixed-angle).
PROTOCOL
Fecal flotation with centrifugation has been 
shown to be the most accurate way to recover 
parasite diagnostic life stages and consistently 
recovers more of these stages than standing 
flotation methods (also known as simple 
flotation):
1. Weigh out 1–3 g of feces.
2. Mix feces with ≈15 mL of flotation 
solution in a cup until homogeneous.
3. Pour the mixture through a tea strainer 
into another fecal cup.4. Pour the strained solution into a 15 mL 
centrifuge tube.
5. If you have a centrifuge with swing 
buckets, fill the tube with flotation solution 
until forming a slight positive meniscus. Do 
not overfill tube. Doing so will cause some 
floating diagnostic stages to be forced down 
the side of tube when the coverslip is placed.
6. Place a coverslip on the tube and put the 
tube in the centrifuge.
Note: Steps 5 and 6 are done only if the 
centrifuge has a swinging-bucket rotor (swing 
head). If the centrifuge has a fixed-angle head 
(fixed head), the tube is spun without being 
filled completely. After centrifuging, the tube 
is moved to a test-tube rack and filled with 
flotation solution until a slight positive 
meniscus forms. A coverslip is then placed on 
the tube, and the tube is allowed to stand for 
an additional 10 min before the coverslip is 
removed and examined.
7. Centrifuge at 1,200 RPM (280 × g) for 
5 minutes.
8. Allow centrifuge to stop without using the 
brake, as it may interfere with the flotation of 
the parasite diagnostic stages.
9. Remove the tube and let it stand for 5–10 
minutes. ( Note: 10 minutes would allow more 
parasite diagnostic stages, if present, to float.).
10. Remove the coverslip and place on a 
glass slide.
11. Systematically examine the entire area 
under the coverslip by using the 10× objective 
lens (100× magnification). The 40× objective 
lens can be used to confirm the diagnosis and 
make measurements; however, with practice, 
most identification can be made at 100× 
No parasitic eggs, oocysts, or cysts seen (or 
“no parasites seen).”
Parasitic eggs, oocysts, or cysts seen (or report 
of specific parasite genera/species seen).
None
None
None

Canine and Feline, Seventh Edition  1523
(continued)  Fecal Flotation
Table 1
Common parasites of dogs and cats found in feces.
Parasite Life StageLocation of Mature 
Life Stage How Infection Happens
Common parasites of dogs with stage of life cycle found in feces
Toxocara canis Large, dark, 
thick-shelled eggSmall intestine In utero  or ingestion of infected paratenic hosts or infective 
larvated eggs or nursing (milk)
Toxascaris leonina Large, light, 
thick-shelled eggSmall intestine Ingestion of infected paratenic hosts or infective larvated 
eggs
Physaloptera  spp. Thick-shelled, 
larvated eggStomach Ingestion of infected intermediate hosts (e.g., insects) or 
paratenic hosts (e.g., frogs, mice)
Taenia  spp. Small egg, with 
hooksSmall intestine Ingestion of metacestode stage in intermediate hosts (e.g., 
rabbits)
Dipylidium caninum Egg packet Small intestine Ingestion of metacestode stage in intermediate hosts (fleas)
Ancylostoma caninum Strongyle-type egg Small intestine Ingestion of L3 from environment, nursing (milk), or skin 
penetration by L3
Uncinaria stenocephala Strongyle-type egg Small intestine Ingestion of L3 from environment or rarely skin penetration 
by L3
Eucoleus boehmi  (formerly known 
as Capillaria boehmi )Bioperculated egg Nasal passages Ingestion of larvated egg or infected intermediate host
Trichuris vulpis Bioperculated egg Cecum, large intestine Ingestion of larvated egg
Eucoleus aerophilus  (formerly 
known as Capillaria aerophila )Bioperculated egg Lungs Ingestion of larvated egg or infected intermediate host
Strongyloides stercoralis Larvae Small intestine Ingestion or skin penetration by L3
Cystoisospora  spp. (formerly 
known as Isospora  sp.)Oocyst Small intestine Ingestion of sporulated oocysts, or cysts in intermediate 
host
Giardia  sp. Cyst Small intestine Ingestion of cysts
Alaria  sp. Egg Stomach, small 
intestineIngestion of mesocercaria in fish, frogs, or rodents
Common parasites of cats with diagnostic life stage found in feces
Toxocara cati Large, dark, 
eggs 
eggs
larvated eggStomach Ingestion of infected intermediate hosts (e.g., insects, 
arthropods) or paratenic hosts (e.g., frogs, mice)
Taenia  spp. Egg Small intestine Ingestion of metacestode stage in intermediate hosts (e.g., 
rodents)
Ancylostoma tubaeforme Strongyle-type egg Small intestine Ingestion of L3 from environment, or skin penetration
known as Capillaria aerophila )Bioperculated eggs Lungs Ingestion of infective larvated egg or infected intermediate 
host
host
Toxoplasma gondii Oocyst Small intestine Ingestion of sporulated oocysts, tachyzoites, or bradyzoites 
in mice or other meat
Aelurostrongylus abstrusus Larvae (L1) Lungs Ingestion of intermediate hosts (snails or slugs) or paratenic 
hosts (mice and birds)
Spirometra  sp. Egg Small intestine Ingestion of plerocercoid in intermediate host (reptile, 
mammals)
Demodex , Cheyletiella , and Otodectes  sp. mites may be seen in fecal flotations. Echinococcus  sp. eggs are similar to Taenia  sp.

1524  Blackwell’s Five-Minute Veterinary Consult  
None
• Insufficient sample size.
• Old samples: the presence of free-living 
nematodes and protozoa.
Species
None
Breed
None
Age
Puppies and kittens should be checked for 
internal parasites and medicated according to 
the recommendations of the American 
Association of Veterinary Parasitologists, 
American Animal Hospital Association, and 
the Companion Animal Parasite Council.
Gender
None
Pregnancy
None
• Sample size can be an issue in anorexic or 
very small animals with minimal fecal output.
• Some eggs ( Trichuris vulpis ) and cysts 
(Giardia  sp.) are shed in low numbers or 
intermittently. If suspicion is high, fecal 
flotation should be run on samples from 3 
consecutive days.
Note that centrifugal flotation is more 
sensitive and accurate than passive flotation.
No. Few technicians are trained in the 
identification of animal parasite diagnostic 
life stages.CAUSES OF ABNORMAL FINDINGS 
(SEE TABLE 1)
• Spurious eggs and oocysts of parasites of other 
animals may be passed in feces of dogs and cats 
when these fed on live animals or carcasses, or 
animal feces (e.g., oocysts of Eimeria , a 
coccidian of birds, rodents, and herbivores).
• Pseudoparasites are common findings in 
fecal flotations, and should not be mistaken 
with parasite diagnostic stages. In fact, pseudo  - 
parasites are structures of free-living organisms 
that may pass in feces or are product of 
environmental contamination (e.g., pollen 
grains, plant hair, mite eggs, grain mites).
• A good-quality microscope with a 
micrometer is required. A micrometer makes 
it possible to measure objects seen under the 
microscope, thus ensuring the accurate 
diagnosis of parasites.
• Giardia  cysts are often mistaken for yeast, 
but Giardia  cysts are all about the same size, 
whereas yeasts vary greatly in size and shape.
• Proper techniques are imperative for the 
accurate diagnosis of intestinal parasites.
• Due to coprophagy, strongyle-type eggs from 
horses or cows, or coccidia oocysts from 
ruminants, rabbits, or birds, may be found in 
canine feces. To determine whether these eggs are 
just passing through, confine the dog away from 
these animals for 24–48 hours and recheck.
• Fecal sedimentation techniques to look for 
trematode (fluke) eggs.
• Baermann technique to look for larvae of 
lungworms (note that some worms that are 
found in the respiratory tract may shed eggs 
that can be seen in flotation, see Table 1).
• In animals with diarrhea, consider 
evaluating fecal cytology, cobalamin, folate, 
and trypsin-like immunoreactivity.SYNONYMS
Fecal float.
SEE ALSO
• Fecal Direct Smear and Cytology (in 
• Tapeworms (Cestodiasis).
• L1 = first-stage larva(e).
• L3 = third-stage larva(e).
• SG = specific gravity.
• Penn Veterinary Medicine, Veterinary 
Parasitology CAL Program: http://cal.vet.upenn.
edu/projects/parasit06/website/index.htm
• University of Wisconsin–Madison, School 
of Veterinary Medicine: Veterinary 
parasitology, http://www.vetmed.wisc.edu/
pbs/vetpara/gallery.html
• Companion Animal Parasite Council: 
Dryden MW, Payne PA, Ridley R, Smith V. 
Comparison of common fecal flotation 
techniques for the recovery of parasite eggs 
and oocysts. Vet Ther 2005, 6:15–28.
Foreyt W, ed. Veterinary Parasitology 
Reference Manual, 5th ed. Ames, IA: Iowa 
State Press, 2001.
Zajac AM, Conboy GA. Veterinary Clinical 
Parasitology, 8th ed. Hoboken, NJ: 
Wiley-Blackwell, 2012.
Authors  Guilherme G. Verocai and Andrew 
R. Moorhead
Patricia A. Payne.Fecal Flotation  (continued)

Canine and Feline, Seventh Edition  1525
  BASICS
• For acquisition of samples of masses, lymph 
nodes, organ cellularity for the purposes of 
• Cytology may identify inflammatory and 
infectious processes and distinguish between 
neoplastic and nonneoplastic conditions.
• Poorly prepared smears can make 
interpretation difficult. Extremely thick 
smears, for example, can limit evaluation of 
individual cell characteristics.
• Evaluation of cutaneous, subcutaneous, 
intracavitary masses.
• Evaluation of lymphadenopathy.
• Evaluation of nodules, masses, or other 
changes within organs.
• Fine-needle aspiration (FNA) is difficult to 
perform on very small masses or those that 
cannot be stabilized.
• FNA entails a risk of hemorrhage when 
used to assess cavitary masses.
• Patients with a condition that includes 
severe bleeding tendencies (e.g., thrombo -
cytopenia or coagulopathy).
• Bleeding, bruising.
• Release of bioactive substances (e.g., mast 
• Potential spread of malignant neoplasia 
(rare).
• Pneumothorax (FNA of lungs).
While risks are minimal when FNA cytology 
of internal organs or masses is performed, 
clients should be advised of the potential for 
hemorrhage or pneumothorax in the case of 
lung aspiration.
All
  PROCEDURE
• None needed for external palpable masses.
• The use of an aseptic skin preparation is 
indicated prior to FNA of internal masses.Anesthesia or Sedation
• Generally, none is needed for external 
palpable masses or lymph nodes.
• Mild to heavy sedation is beneficial for 
obtaining diagnostic ultrasound-guided or 
bone FNA.
Any that enables optimal access to the site 
being aspirated.
For minor bruising or bleeding at the FNA 
site.
• A needle of appropriate gauge—a 22-gauge, 
1-inch needle is appropriate for most 
cutaneous and subcutaneous masses. Longer 
needles may be used for intracavitary or 
ultrasound-guided aspirates.
• A 6- or 12-mL syringe.
• Glass microscopic slides.
TECHNIQUE
Sample Collection
Needle Only
The mass or tissue is stabilized as much as 
possible while the needle is inserted into it 
and vigorously moved in and out of it in 
several directions. The needle is then 
withdrawn, a syringe filled with air is attached 
to the needle hub, and pressure is applied to 
the plunger to empty the needle’s contents 
onto a glass slide. If blood or liquid is 
observed in the hub of the needle during this 
procedure, the FNA should be discontinued 
and the slide prepared.
Needle and Syringe with Continuous 
Negative Pressure
possible, and the needle with attached empty 
syringe is inserted into the mass or tissue. 
Negative pressure is then applied to the 
syringe and maintained while the needle is 
redirected several times within the mass or 
tissue. Negative pressure is then released, and 
the needle with attached syringe is withdrawn. 
The syringe is detached from the needle, 
filled with air, reattached to the hub of the 
needle, and pressure is applied to the plunger 
to empty the needle’s contents onto a glass 
slide. If blood or liquid is observed in the hub 
of the needle during this procedure, the FNA 
should be discontinued and the slide prepared.
Needle and Syringe with Repeated Negative 
Pressure
possible while the needle with attached empty 
Negative pressure is applied to the syringe 
and released several times. The needle can be 
redirected and negative pressure again applied and released several times. This can be 
repeated in several directions within the mass 
or tissue. Once the sample has been collected, 
negative pressure is released, and the needle 
with attached syringe is withdrawn. The 
syringe is detached from the needle, filled 
with air, reattached, and pressure is applied to 
Slide Preparation
Flat Spreader Slide T echnique
A second slide is laid gently atop and perpen  - 
dicular to the slide containing the sample and 
gently drawn down the length of the sample 
slide to achieve an even, thin layer of cells.
Angled Spreader Slide T echnique
A second slide is positioned over the slide 
containing the sample and angled at 45° with 
the sample located in the small angle created 
between the two slides. The spreader slide is 
then drawn along the sample slide so that the 
cells are spread in an even layer down the 
latter slide’s length. This technique, similar to 
that used for making a blood smear, may 
result in the rupture or breakage of cells from 
FNA.
• Air-dried samples can be stored at room 
• Samples should be fixed and stained as soon 
after collection as possible (ideally within 3–7 
days) for optimal assessment of cellular 
• Once fixed and stained, FNA smears are 
stable for months to years, depending on 
storage conditions.
Generally, no post-procedure monitoring is 
required, although if FNA is performed on 
highly vascular internal masses or tissues, 
monitoring for evidence of hemorrhage (i.e., 
mucous membrane color, attitude, with or 
without PCV and total solids) should be 
performed in the hours after the procedure.
None
None
None
None
Immediate

1526  Blackwell’s Five-Minute Veterinary Consult  
A bullet-shaped tissue smear that extends 
approximately one-half to two-thirds the 
length of the slide.
• Abnormal cell ratios, numbers, or types.
• The presence of infectious agents.
• The presence of neoplastic cells.
• The presence of abnormal inflammation.
None
None
None
• Hemorrhage with numerous RBCs evident 
cytologically may limit interpretation.
• Failure to fix and stain slides within 1–2 
weeks may alter cellular characteristics and 
limit value of interpretation.Influence of Signalment on Performing 
Species
None
Breed
None
Age
None
Gender
None
Pregnancy
None
Cytologic examination of FNA samples is a first 
step in assessing masses, lymphadenopathy, and 
other organ changes. Examination of prepared 
slides can provide information on potential 
pathology affecting the tissue sampled, 
including hyperplastic, reactive, inflammatory, 
and neoplastic changes. Depending on results, 
a follow-up incisional or excisional biopsy may 
be indicated for definitive diagnosis.
• A biopsy with a histopathologic diagnosis 
to confirm the FNA results if they are equivocal or if the biopsy is indicated for 
definitive diagnosis and grading.
• Coagulation testing if there is a concern for 
hemorrhage during the procedure.
SYNONYMS
Fine-needle aspiration biopsy.
SEE ALSO
• Blood Smear Preparation (in Appendix X).
• Impression Smear (in Appendix X).
• Ultrasound-Guided Mass or Organ 
Aspiration (in Appendix X).
Cowell RL, Tyler RD, Meinkoth JH, eds. 
Raskin RE, Meyer DJ, eds. Atlas of Canine 
and Feline Cytology, 2nd ed. Philadelphia, 
PA: W.B. Saunders, 2001.
Consulting Editor  Benjamin M. BrainardFine-Needle Aspiration  (continued)

Canine and Feline, Seventh Edition  1527
  BASICS
Tissue
The abdominal and thoracic cavities normally 
contain a small amount of fluid that is an 
ultrafiltrate of blood which serves to provide 
lubrication that enables frictionless movement 
of adjacent organ surfaces and the body cavity 
walls. An increased amount of fluid in any 
body cavity lined by mesothelial cells is 
termed an effusion. An effusion is not a 
disease itself but, rather, the result of a 
pathologic alteration in the process of fluid 
production and/or removal, or an accumula­
tion from an ectopic source.
A comprehensive fluid analysis is a rapid, 
simple, inexpensive, and reasonably safe way of 
gaining useful information regarding disease 
processes that cause effusions. Classification 
schemes are designed to help clinicians generate 
a short list of differential diagnoses and 
characterize an effusion based on the primary 
underlying pathophysiologic mechanism.
Effusions are classified as a pure transudate, 
modified transudate, exudate, hemorrhagic 
effusion, or neoplastic effusion (see Table 1). 
Exudates are further divided into subcategories 
of septic or nonseptic exudates. The classifi­
cation of these fluids is based on three 
parameters: total protein, nucleated cell 
counts (NCCs), and cytologic appearance.
Pure transudates usually form via a passive 
process resulting from decreased colloid 
osmotic pressure (vs. an alteration in capillary 
permeability). They most frequently form as a 
result of hypoproteinemia from either 
increased loss or decreased production of 
albumin (the primary contributor to plasma 
colloid osmotic pressure). Infrequently, 
transudates precede modified transudates 
before developing an increased NCC or 
protein concentration.
A modified transudate occurs when 
vascular fluids leak from normal, noninflamed 
vessels (e.g., via increased capillary hydrostatic 
pressure or lymphatic obstruction). This fluid 
is modified by the addition of protein or cells 
(compared to a pure transudate). A chylous 
effusion is a specialized type of modified 
transudate that results from leakage of 
noninflamed lymphatics into the thoracic 
and/or abdominal cavity.
Exudates are the result of increased 
vascular permeability and inflammation and 
are further classified as septic or nonseptic 
(sterile) depending on whether infectious 
agents are present in the fluid. Nonseptic 
exudates may result from conditions that cause longstanding modified transudates, as 
well as from other, more inflammatory disease 
conditions. Hemorrhagic effusions can be 
caused by ruptured vessels or organs.
Neoplasia is a common underlying cause 
of effusions in dogs and cats although 
neoplastic cells may not be identified on 
cytologic preparations (i.e., neoplastic cells 
may not exfoliate into the effusion). 
Furthermore, neoplasia may cause various 
effusions, including modified transudates, 
exudates, and hemorrhagic effusions. The 
term neoplastic effusion is reserved for fluids 
in which a neoplastic cell population is 
definitively identified. However, this 
determination is frequently difficult because 
neoplastic cells are absent or are present in 
low numbers, and reactive mesothelial cells 
often have cytologic criteria that mimic 
• Accumulation of fluid because of an 
• Suspicion of neoplasia or sepsis.
None
During acquisition of fluid (see 
Thoracocentesis and Fluid Analysis, 
Pericardiocentesis, and Abdominocentesis and 
Fluid Analysis):
• T rauma to surrounding viscera (i.e., 
perforation, laceration).
Sampling of cavitary effusions typically is 
minimally invasive with minimal associated 
risk and discomfort for the animal, and may 
have therapeutic benefits (e.g., pericardio ­ 
centesis).
  SAMPLE
2–6 mL of fluid.
• Collect the sample into EDTA ­containing 
tube to prevent clotting and to optimize 
preservation of cells.
• Place an aliquot into a sterile tube without 
EDTA if bacteriologic culture is anticipated 
(EDTA is bacteriostatic) or if biochemical testing is required.
• Prepare smears immediately if the sample 
will not be processed within 1–2 hours after 
• T ransport the fluid sample chilled, with any 
accompanying slides at room temperature.
• Refrigerate fluid.
• Stores slides at room temperature, away 
from light or humidity.
• Fluid.
• Room temperature: 2–4 hours.
• Refrigerated (4°C): 24–36 hours.
• Unstained smears of fluid can be stored for 
1 week or more. Stained slides can be stored 
for months to years.
PROTOCOL
In­house fluid analysis:
• Note the gross appearance of fluid including 
color and clarity.
• Prepare smears of fluid by using the same 
technique used to make blood smears. Smears 
should be thin enough to dry quickly. Be sure 
that the smear has a stainable feathered edge.
• Air­dry smears and stain with a Romanovsky ­ 
type cytology stain.
• Perform a NCC via hematology analyzer or 
hemocytometer.
• Centrifuge an aliquot of fluid and note the 
appearance of the supernatant.
• Determine the total protein of supernatant 
via refractometer.
• If the NCC is <3,000/ μL, prepare 
additional smears of sedimented cellular 
material, using either a centrifuge (with 
resuspension of the pellet) or a cytospin 
device.
No excess free fluid should be found in the 
pleural cavity, peritoneal cavity, and 
pericardium.
The presence of an abnormal, increased 
amount of fluid within a body cavity
Evidence of septic peritonitis, uroabdomen, 
or bile peritonitis requires immediate 
None

1528  Blackwell’s Five-Minute Veterinary Consult  
• Corticosteroids may artifactually decrease 
the percentage and total number of 
• Antibiotic administration greatly hinders 
the cytologic identification of bacteria, and 
can result in false ­negative culture results. In 
patients that have received antibiotics that 
develop exudates characterized by degenerate 
neutrophils, a septic effusion should be a 
primary differential, even in the absence of 
intracellular microorganisms.
• High triglyceride concentration in chylous 
effusions, or other causes of turbidity, may 
artificially increase protein determination by 
refractometry. If possible, clear such samples 
prior to determining protein concentration by 
refractometer.
• The dilutional effect of urine in uroperito­
neum may decrease the protein concentration 
and NCC.
• Peracute hemorrhagic effusions may not 
have detectable erythrophagocytosis.
• The protein concentration in an effusion 
can be affected by serum protein concen­
tration (e.g., mildly increased with dehydration; 
decreased with protein ­losing enteropathies 
or nephropathies) regardless of the effusion 
mechanism.
preparations (e.g., direct or sediment smears) 
may lyse cells.
• Delayed processing may lead to in vitro  
artifacts such as erythrophagocytosis, lysed 
cells, and/or poor cellular preservation. 
Bacterial overgrowth may occur if a 
preservative is not used or the specimen is not 
refrigerated.Influence of Signalment
Species
None
Breed
None
Age
None
Gender
None
Pregnancy
None
N/A
Valid If Run in Human Lab?
Yes.
• T urbidity caused by lipids (e.g., chylous 
effusion) will not clear with centrifugation, 
unlike the turbidity caused by an increased 
NCC.
• Inadvertent venipuncture or aspiration of 
the spleen is possible at time of collection. 
T rue hemorrhagic effusions should have 
the same color and turbidity throughout 
the draw, whereas with accidental veni ­
puncture and splenic aspirate samples 
usually change color and turbidity during 
collection. Splenic aspirates may also clot, 
while effusion generally will not, unless 
peracute.
• Lipid can be an irritant and chronic chylous 
effusions may have a mixed inflammatory cell 
population, including neutrophils (which 
may ultimately predominate) and macrophages, 
in addition to lymphocytes.• If intracellular infectious agents are 
identified, the effusion is septic, regardless of 
protein concentration and NCC.
• If fluid collected by abdominocentesis has 
low cellularity, abundant mixed bacteria, 
ingesta, and/or intestinal parasite ova, 
consider accidental enterocentesis or acute 
intestinal perforation.
• The distinction between reactive 
mesothelial cells and a true neoplastic cell 
population (carcinoma or mesothelioma) is 
often difficult to impossible with cytology 
alone, since reactive mesothelial cells may 
exhibit significant atypia mimicking 
malignancy. Correlation with observation of a 
“mass effect” on imaging may assist in making 
this distinction, but additional diagnostics are 
often needed, such as cytopathologic/
histopathologic evaluation of any masses.
• Albumin.
• Creatinine (fluid)—a value of ≥2 ­fold 
serum creatinine and ≥1.4 fold serum 
potassium is diagnostic for uroperitoneum.
• Total bilirubin (fluid)—a value of ≥2 ­fold 
serum bilirubin is diagnostic for bile 
peritonitis. Bile crystals are frequently 
observed cytologically, as well.
• T riglycerides (fluid; for diagnosis of 
chylothorax)—greater than serum triglycerides
• Glucose (fluid)—a value of 38 mg/dL less 
than that for blood glucose has been suggested 
to be specific for sepsis, but low glucose may 
simply reflect the concurrent elevated NCC 
and subsequent utilization by leukocytes, and 
samples may be analyzer dependent.
• Microbial culture and sensitivityTable 1
Classification of effusions.
Classification Gross Appearance Protein (g/dL) Cells/ μL Cell Types Present
Pure transudate Colorless; clear <2.5 <1,500 Mixed (macrophages, nondegenerate neutrophils, 
mesothelial cells)
Modified 
transudateWhite to red; variable 
turbidity2.5–5.0 1,000–7,000 Mixed (nondegenerate neutrophils, macrophages, 
mesothelial cells, small lymphocytes)
Chylous effusionaMilky white, tan, or pink 2.5–5.0 1,000–7,000 Predominantly small lymphocytes
ExudatebAmber, white, or red; turbid 
or cloudy>3.0 >7,000 Predominantly neutrophils
Hemorrhagic 
effusioncPink or red; cloudy or 
opaqueVariable Variable Similar to peripheral blood but lacks platelets and 
may have erythrophagia
Neoplastic effusion Variable Variable Variable Neoplastic cells present
a Chylous effusions have a triglyceride concentration of >100 mg/dL and a fluid cholesterol/triglyceride ratio of <1.0.
b Further classification of exudates depends on whether microorganisms are present (i.e., septic versus nonseptic).
c The PCV of fluid is ≥10–25% of the PCV of peripheral blood.Fluid Analysis  (continued)

Canine and Feline, Seventh Edition  1529
SYNONYMS
Body cavity effusion
SEE ALSO
• Abdominocentesis and Fluid Analysis (in 
• Ascites.
• Bile Peritonitis
• Chapters on cardiac disease.
• Chapters on hepatic disease.
• Sepsis and Bacteremia.• Thoracocentesis and Fluid Analysis (in 
• IL­5 = interleukin 5.
• NCC = nucleated cell count.
http://eclinpath.com/cytology/effusions ­2/
Thompson CA, Rebar AH. Body cavity 
fluids. In: Canine and Feline Cytology: A 
Color Atlas and Interpretation Guide, 3rd 
ed. St. Louis, MO: Elsevier, 2016, pp. 
191–219.Valenciano AC, Arndt TP , Rizzi TE. 
Effusions: abdominal, thoracic, and 
pericardial. In: Valenciano AC, Cowell RL, 
eds., Cowell and Tyler’s Diagnostic 
Cytology and Hematology of the Dog and 
Cat, 4th ed. St. Louis, MO: Elsevier, 2014, 
pp. 244–265.
Author  Rebekah G. Gunn ­Christie
Consulting Editor  Benjamin M. BrainardTable 2
Type of Effusion and Mechanisms Possible Causes
Pure transudate
Decreased plasma colloidal osmotic pressure (i.e., 
hypoalbuminemia)—more common
Early cardiac disease or portal hypertensionDecreased production of albumin
Liver failure
Maldigestion/malabsorption
Starvation
Increased loss of albumin
Protein-losing nephropathy
Protein-losing enteropathy
Other
Iatrogenic overhydration
Modified transudate
Increased capillary hydrostatic pressure
Lymphatic obstructionCardiac disease
Portal hypertension
Neoplasia
Acute organ torsion
Chylous effusion
Leakage of lymphatics from noninflamed vesselsCardiac disease
Hernia
Neoplasia
Trauma
Lung torsion
Intestinal lymphangiectasia
Mediastinal granuloma
Exudate
Increased vascular permeability and inflammation caused by 
septic and nonseptic etiologiesUroperitoneum
Bile peritonitis
Feline infectious peritonitis
Inflammation and/or infection of internal organs
Foreign bodies
Neoplasia
Eosinophilic effusion
Eosinophils >10% of the NCC
Secretion of IL- 5 by sensitized T-lymphocytes, mast cells, or 
neoplastic cellsNeoplasia (e.g., mast cell tumor, lymphoma, carcinoma)
Infection (e.g., fungus, parasite, protozoa)
Other eosinophilic inflammatory process such as 
eosinophilic gastritis
Hemorrhagic effusion
Ruptured vessels
CoagulopathiesTraumatic injury
Rodenticide toxicity
Neoplasia
Neoplastic effusion
Exfoliation of identifiable neoplastic cells into fluidLymphoma and other “round” cell tumors
Carcinoma
Mesothelioma
Sarcoma (often poorly exfoliative)(continued)  Fluid Analysis

1530  Blackwell’s Five-Minute Veterinary Consult  
Glucose Curve
  BASICS
Whole blood.
• A method of evaluating glucose control in 
diabetic dogs or cats.
• Serial blood glucose (BG) measurement 
enables assessment of the effect of food and 
medication (insulin or oral hypoglycemic 
drugs) on glucose control. The dose, and, if 
necessary, the type, of medication (e.g., 
intermediate-acting vs. long-acting insulin) 
can be altered, depending on results.
• The lowest (nadir) and highest BG 
concentrations should be noted, as well as the 
duration of action of insulin (the number of 
hours the glucose is in a desired range, 
provided the nadir is acceptable).
◦ Hypoglycemia (a BG concentration of 
<60 mg/dL) or a rapid drop in glucose 
concentration can result in rebound 
hyperglycemia or the Somogyi phenomenon, 
whereby counterregulatory hormones, 
notably glucagon, epinephrine, and 
corticosteroids, cause a variable period of 
hyperglycemia after hypoglycemia occurs.
▪ The occurrence of the Somogyi 
phenomenon is debatable and some 
internists prefer the term posthypogly -
cemic hyperglycemia or glucose 
variability because the link between 
hypoglycemia and hyperglycemia is 
• There is significant variation in BG curves 
from day to day even with no change in 
insulin dose or feeding. A curve should always 
be interpreted in conjunction with 
information on the patient’s appetite, thirst, 
urinations and energy level.
• Control of clinical signs rather than glucose 
concentration is the overall goal with diabetic 
patients.
• To regulate a new diabetic patient.
• To investigate a poorly controlled diabetic 
patient.
• To diagnose transient diabetes mellitus, a 
temporary or permanent resolution of 
diabetes in cats.
• Inappetence or illness on the day of the test.
• Hypoglycemia (a BG concentration of <60 
mg/dL) on admission: In this case, cancel the 
BG curve analysis and recommend a 10–25% 
insulin-dose reduction.
• Stress hyperglycemia—if a patient, especially 
a cat, is very anxious, the curve may be 
meaningless. If glucose readings in an extremely stressed patient are normal, insulin 
overdosage may be suspected.
None
• The goal for diabetic management is to 
maintain daily BG concentrations between 
100 and 300 mg/dL with an average glucose 
<250 mg/dL. Measurements outside that 
range may require a dose adjustment, an 
alternative insulin type, or further investi -
gation or monitoring.
• Owners can monitor glucose at home by 
using lancets to obtain a small drop of blood 
from the marginal ear vein, metacarpal pad, 
foot pad, ventral medial pinna, buccal 
mucosa of a lip (dogs), or elbow calluses 
(dogs).
◦ Warming the site first with a dry (to 
avoid diluting sample) warm cloth will 
improve sample size.
◦ Glucose should be measured by using 
portable veterinary-specific glucometers 
that use the least amount of blood, such as 
the AlphaTRAK 2 (Zoetis, Parsippany, NJ).
◦ Glucometers designed for human usage 
measure lower than the actual reading, 
which may result in falsely low BG 
readings.
• Owners need to be instructed carefully in 
the home use of glucometers and informed 
about calibration and coding of the devices 
according to the manufacturer’s directions.
• Newer long-term interstital devices (e.g., 
freestyle Libre, Abbott, N. Chicago, IL) may 
allow generation of BG curve data at home, 
over longer periods of time (e.g., 14 days), 
using smartphone-based technology.
Endocrine and metabolic.
  SAMPLE
• Generally, a very small amount of blood 
(<0.2 mL) is obtained by venipuncture, using 
an insulin syringe or pricking the skin with a 
lancet:
◦ The goal is to be minimally invasive 
while enabling multiple sequential sample 
collections.
• When using a lancet, the glucometer with 
test strip inserted is held to the drop of blood, 
which is then drawn up by capillary action.
• For in-hospital curves a glucometer is 
typically used but if a larger amount of blood 
is obtained, glucose can be measured with a 
point of care machine, although the same 
machine should be used for analyzing all 
samples in the curve.SAMPLE HANDLING
The sample should be analyzed immediately.
Immediate analysis is recommended.
If measuring serum glucose, the blood sample 
should be separated quickly to avoid spurious 
PROTOCOL
• The patient is admitted to the hospital 
shortly after being fed and given insulin at 
home.
• The owner’s feeding schedule should be 
followed for the remainder of the day.
• Appetite and stress level are noted during 
the day.
• BG concentration is measured every 2 
hours for 10–12 hours. Collect blood from 
any easily accessible peripheral vein or 
pricking skin with lancet, using minimal 
restraint to avoid stress hyperglycemia.
• Measure glucose by using a portable glucose 
meter or a point-of-care analyzer.
• Note the BG nadir, duration of effect 
(number of hours BG concentration between 
60–300 mg/dL), and highest BG 
• BG curves are typically repeated 7–14 days 
following an insulin dose change. New 
diabetic patients may require 3–4 curves to 
determine an insulin dose that controls 
clinical signs. Cats going into remission also 
require multiple curves while they are tapered 
off insulin.
• Dogs and cats—the ideal BG concen -
tration range is 80–300 mg/dL with an 
average BG <250 mg/dL and a nadir of 
80–150 mg/dL.
• Normal or below-normal BG concentration 
readings in cats with diabetes mellitus suggest 
transient diabetes, especially if normal findings 
are repeatable with dose reduction or 
discontinuation of insulin administration.
BG concentrations above or below ideal range 
require evaluation.
• A BG concentration <60 mg/dL requires 
evaluation to ensure patient is not exhibiting 
clinical signs such as twitching, stumbling, or 
mental dullness (may need to treat with IV 
glucose or oral glucose if patient is able to 
eat). Recheck BG hourly until normal, consider 
potential insulin dose adjustment to avoid 
subsequent hypoglycemic events.

Canine and Feline, Seventh Edition  1531
• A persistently high BG concentration (>600 
mg/dL) may be associated with hyperglycemic 
• Glucometers are not designed to measure 
glucose in serum or plasma.
• Inaccurate readings can also occur with anemia, 
polycythemia, inadequate sample size, expired 
glucose strips, miscoded meters, contamination 
(e.g., sugar on skin of pet or human).
• A correction formula for the Alpha- 
TRAK 2 has been developed to account for 
variation in patient PCV:
Corrected glucose = glucose reading  
+ ([1.6 × PCV(%)] − 81.3) (dogs)
+ ([1.17 × PCV(%)] − 50.2) (cats)
None
The administration of drugs such as 
corticosteroids and megestrol acetate cause 
insulin resistance that predisposes patients to 
diabetes or worsening glucose control.
Any underlying disease can make diabetes 
more difficult to regulate: especially hyper -
adrenocorticism, infection, pancreatitis, 
acromegaly, or thyroid disease, as well as 
diestrus.
• Stress hyperglycemia in cats and, to a lesser 
degree, in dogs may inappropriately increase 
the BG concentration.• Failure to separate serum promptly may 
falsely lower the BG concentration when the 
assay relies on serum sample.
• Sugary food on skin of patient or person 
obtaining blood sample may falsely increase 
Species
None
Breed
None
Age
None
Gender
Intact females with diabetes are very difficult 
to regulate and should be spayed.
Pregnancy
The same as for gender.
be interpreted in conjunction with information 
on the patient’s appetite, thirst, urinations 
and energy level.
• Control of clinical signs rather than 
glucose levels is the overall goal with 
diabetic patients.
• Handheld portable glucometers may 
overestimate or underestimate glucose levels 
when compared to reference methods. 
Veterinary-specific glucometers are more 
accurate and validated for dogs and cats, and 
N/A
Yes.CAUSES OF ABNORMAL FINDINGS
See Table 1.
• BG curves are only one indicator of diabetic 
control, and results can vary from day to day, 
even when there is little change in the patient’s 
status. Therefore, the results should be 
interpreted with the animal’s clinical signs (e.g., 
presence of PU/PD, polyphagia, weight loss, 
neuropathy). If the patient appears well (no PU/
PD, stable weight, active), then changes made 
may be small or the curve might be repeated.
• Other reasons for persistent hyperglycemia 
(BG concentrations >300 mg/dL) are 
mishandling of insulin, poor injection 
technique, inadequate absorption, and insulin 
resistance (e.g., infection, drugs, hyperadreno -
corticism, diestrus, acromegaly, hypo -
thyroidism, hyperthyroidism.
• It is important that portable glucometers be 
coded correctly and that the test strips are 
correct and in date.
• Serial urine glucose testing can enable 
veterinarians to make some dose increases in 
new diabetic patients before fine-tuning with 
a BG curve.
• Measurement of serum fructosamine 
concentration can be used in addition to 
analysis of BG curves and, in fractious 
animals, may replace the analysis of a BG 
curve. If fructosamine is normal to low-
normal in hypoglycemic patients, it supports 
insulin overdose and, in cats, potential 
• Continuous glucose monitoring using 
interstitial (subcutaneous) sensors (e.g., 
CGMS System Gold; Medtronic MiniMed, Table 1
Interpretation of curve.
Abnormal Finding Suggested Response
Nadir and peak BG concentration are greater 
than the idealIncrease the dose of insulin
The nadir is acceptable, but the effect of 
insulin was of insufficient durationSwitch to a longer acting insulin: Dogs: Switch from NPH (neutral 
protamine Hagedorn) insulin to lente insulin or insulin detemir
Cats: If not already on a long acting insulin, switch to insulin 
glargine or insulin detemir
Hypoglycemia Decrease the dose by 10–25% and, in cats, consider transient 
diabetes mellitus
Persistent hyperglycemia may be caused by 
insulin overdose (post hypoglycemic 
hyperglycemia) insulin underdose, or insulin 
resistance).Consider increasing insulin dose, switching insulin type and if the 
insulin dose is >1.5 U/kg bid, evaluate for causes of the insulin 
resistance(continued)  Glucose Curve

1532  Blackwell’s Five-Minute Veterinary Consult  
Minneapolis, MN) enables continuous 
interstitial fluid glucose concentration to be 
measured for up to 14 days. The newer Libre 
Freestyle Flash glucose monitoring system is 
cost effective, easy to use, is accurate in 
diabetic dogs, and is being evaluated for use 
in diabetic cats.
SYNONYMS
None
SEE ALSO
• Diabetes Mellitus Without 
Complication—Cats.
Complication—Dogs.
• PU/PD = polyuria/polydipsia. INTERNET RESOURCES
• AAHAguidelines: https://www.aaha.org/
aaha-guidelines/diabetes-management/
diabetes-management-home/
• Canine Diabetes: http://www.caninediabetes.
org
• Feline Diabetes: http://www.felinediabetes.
com
• Pet Diabetes support site: http://www.
petdiabetes.com
Behrend E, Holford A, Latham P , Rucinsky 
R, et al. 2018 Diabetes management 
guidelines for dogs and cats. J Am Anim 
Hosp Assoc 2018, 54:1–21
Corradini S, Pilosio B, Dondi F , Linari G, 
et al. Accuracy of a flash glucose monitoring 
system in diabetic dogs. J Vet Intern Med 
2016, 30:983–988Fleeman L, Rand J. Evaluation of day to day 
variability of serial blood glucose 
concentration curves in diabetic dogs. J Am 
Vet Med Assoc 2003, 222:317–321.
Kley S, Casella M, Reusch C. Evaluation of 
long-term home monitoring of blood 
glucose concentrations in cats with diabetes 
mellitus: 26 cases (1999–2002). J Am Vet 
Med Assoc 2004, 225:261–266.
Lane SL, Koenig A, Brainard BM. Formulation 
and validation of a predictive model to 
correct blood glucose concentrations obtained 
with a veterinary point-of-care glucometer in 
hemodiluted and hemoconcen-  
trated canine blood samples. J Am Vet Med 
Assoc. 2015, 246:307–312.
Reusch C, Kley S, Casella M. Home 
monitoring of the diabetic cat. J Feline Med 
Surg 2006,8:119–127.
Author  Orla Mahony
Consulting Editor  Benjamin M. BrainardGlucose Curve  (continued)

Canine and Feline, Seventh Edition  1533
Impression Smear
 BASICS
• Impression smears obtained from superfi-
cial lesions or from tissue biopsy samples may 
reveal cellular details not visible after 
collection and processing for histologic 
• Individual cell types, including infectious 
organisms and neoplastic cells, may be 
identified on impression smear cytology, 
which provides more rapid assessment than 
histologic examination.
None
None
None
All
 PROCEDURE
None
None
None
None
• A paper towel for blotting.
• A scalpel blade.
TECHNIQUE
Impression smears may be made directly from 
superficial ulcerated lesions or from harvested 
biopsy tissue.
• Directly from a lesion: An imprint is made 
by touching the center of a clean glass slide to 
the uncleaned lesion. After an initial impression 
smear, the lesion can be gently blotted and 
cleaned with saline solution and gauze and a 
second impression made.
• For a harvested biopsy tissue: A freshly 
cut surface is exposed by sectioning the tissue biopsy sample with a scalpel blade 
(this is not required if the sample being 
evaluated is freshly removed via needle or 
punch biopsy). An important aspect of 
obtaining diagnostic impression smears is 
blotting the tissue on a clean absorbent 
material, such as a paper towel, to remove 
excess blood, moisture, and tissue fluid 
prior to imprinting the tissue on a slide. 
The blotted tissue can be gently touched 
onto the middle of a clean glass slide and 
lifted off. Multiple impression smears may 
be made onto separate glass slides.
• Samples should be fixed and stained as 
soon after collection as possible (ideally 
within 3–7 days) for optimal assessment of 
cellular morphology.
N/A
N/A
N/A
N/A
N/A
N/A
 INTERPRETATION
• A blot of tissue centered on the glass slide.
• Identification of cells normally seen in 
sampled tissue.
• Abnormal ratios, numbers, or types of cells 
present.
• Infectious agents.
• Neoplastic cells.
None
None
NoneProcedure Techniques or Handling That 
• Failure to blot the sample adequately prior 
to making an impression smear may obscure 
• Failure to fix and stain slides within 3–7 
days may alter cellular characteristics and 
limit the value of the interpretation.
Species
None
Breed
None
Age
None
Gender
None
Pregnancy
None
• Impression smears are simple to make and 
may reveal cellular details not visible following 
• Even if submitting biopsy samples for histo  - 
pathology, impression smear evaluation can 
give valuble clues to the origin of disease so 
that treatment may be started while waiting 
for histopahologic results.
• Fine-needle aspiration and cytology.
• Biopsy with histopathologic evaluation.
SYNONYMS
• Touch prep.
• Touch prep cytology.
SEE ALSO
Fine-Needle Aspiration (in Appendix X).
PA: WB Saunders, 2001.

1534  Blackwell’s Five-Minute Veterinary Consult  
  BASICS
• Diagnostic and therapeutic procedure 
undertaken to relieve cardiac compression 
caused by pericardial effusion (PE):
◦ PE may be neoplastic, idiopathic, 
traumatic, infectious, inflammatory, 
hemorrhagic, or metabolic in origin, or may 
result from late-stage congestive heart 
◦ Chronic PE has gradual onset of clinical 
signs (weakness, ascites, pleural effusion) 
and a globoid cardiac silhouette radio  - 
graphically.
◦ Acute PE causes rapid onset of clinical 
signs (collapse, shock, sudden death).
• Cardiac tamponade is hemodynamic 
instability (cardiogenic shock) resulting from PE:
◦ Occurs when effusion elevates intraperi -
cardial pressure, exceeding right-sided 
diastolic intracardiac pressures.
◦ Observed echocardiographically as partial 
collapse of the right heart in diastole.
◦ Characterized clinically by shock (collapse, 
hypotension, tachycardia); necessitates 
emergency pericardiocentesis (PC).
◦ Tamponade causes one ventricle to fill at 
the expense of the other, creating pulsus 
paradoxus, a decrease in peripheral pulse 
pressure on inspiration.
◦ Intrapericardial pressure, not the effusion 
volume per se, determines clinical and 
hemodynamic severity.
• Medical therapies (e.g., diuretics) are 
relatively contraindicated (an exception is PE 
secondary to CHF), and PC is necessary to 
stabilize the patient.
• PE producing clinical signs of cardiac 
• Diagnostic sample acquisition.
• An insufficient volume of PE such that the 
risk of PC outweighs potential benefit.
• Relative contraindications include PE 
secondary to coagulopathy or endocardial 
splitting where relief of pericardial pressure 
may perpetuate hemorrhage.
• Not indicated for distention of the 
pericardium by solid tumors or abdominal 
contents.
• Minimize complications by careful 
preparation and technique.
• Puncture of cardiac chambers or great vessels.
• Ventricular arrhythmias.• Coronary laceration causing myocardial 
ischemia or infarction.
• Exsanguination (more likely to occur from 
failure to confirm the correct catheter 
position resulting in evacuation of blood from 
a ventricular chamber, rather than from 
cardiac laceration).
• Death.
• Pulmonary laceration or hemorrhage.
• Failure to relieve cardiac tamponade or 
obtain a diagnostic PE sample.
• Constrictive or effusive-constrictive 
pericardial disease (late complication).
• Clients should be informed of potential 
risks and complications of the procedure.
• The cause of the PE may not be known at 
the time of PC. Hemangiosarcoma is a 
common cause with a poor long-term 
• PC may exacerbate hemorrhage of tumors 
and may worsen tamponade or precipitate 
• Effusions may recur in the near or far 
future. Recurrences are cause dependent and 
difficult to predict.
  PROCEDURE
• Rapid IV fluid administration is indicated 
to treat hypovolemic shock (from hemorrhage 
or third space fluid losses due to right-sided 
heart failure), and this should be administered 
during preparation for PC. The more 
debilitated the patient is, the greater is the 
need for the procedure.
• An IV catheter facilitates fluid resuscitation, 
sedation, and treatment of ventricular 
• Echocardiographic diagnosis of small 
cardiac tumors may be facilitated by the 
presence of PE. Ultrasound examination of 
the heart should precede PC if patient is 
stable.
• The more debilitated the patient is, the 
lesser the need for sedation.
• The author prefers IV sedation with 
butorphanol (0.2 mg/kg). Avoid agents 
promoting hypotension (e.g., acepromazine).
Left lateral recumbency is preferred to 
facilitate directing of catheter toward the right ventral caudal aspect of the heart. Some 
localized PE may not accessible from this 
approach. With ultrasound guidance, sternal 
recumbency may allow an appropriate 
window.
• ECG monitoring (for ventricular arrhythmias) 
by a designated assistant during the 
• Once the first sample of PE is removed, it 
should be observed for coagulation; if the 
sample clots, the catheter is likely in the 
heart, rather than pericardial sac.
Equipment or Supplies (see Figure 1)
• A large-bore, over-the-needle catheter is 
typically used: 18–14 gauge, 2–5½ inches, 
depending on patient size.
• Small (3–6 mL) and large (10–50 mL) 
syringes.
• Three-way stopcock.
• Extension tubing.
• Collection: bowl, tubes for cytological 
evaluation (EDTA) and culture submission.
• No. 11 surgical blade.
• Sterile surgical gloves (see Figure 1).
• 2% Lidocaine for local anesthesia and for 
treatment of ventricular arrhythmias:
◦ Calculate dose of lidocaine for anti-
arrhythmic therapy (2 mg/kg IV).
TECHNIQUE
• Default catheter entry location is at 
5th–7th intercostal space of right ventral 
thorax, at the level of costal-chondral 
junction.
◦ The hair is clipped, and the suitability of 
the site is confirmed using ultrasound.
• The site is aseptically prepared, and can be 
infiltrated deeply with lidocaine (0.5–3.0 mL, 
not to exceed 2 mg/kg).
• A no. 11 blade is used to create a small 
stab incision through skin at site of catheter 
entry.
• Catheter entry should be near the center of 
the rib space, erring toward the cranial aspect 
of the rib:
◦ The catheter should intersect the 
pericardium at the right ventral aspect, so 
catheter is advanced dorsally and cranially 
(i.e., toward the opposite scapula) (see 
Figure 2).
◦ Prior to insertion, the operator can attach 
a sterile 3-mL syringe to the catheter stylet.
▪ Once catheter tip is through skin, a 
small amount of suction is applied to the 
syringe; this ensures that PE will be 
aspirated as soon as the stylet tip penetrates 
the pericardium.
◦ ECG is monitored closely during catheter 
advancement. A burst of ventricular 
premature complexes suggests that the stylet 
tip has contacted the epicardium. The 
catheter should be retracted until arrhythmia 
abates.

Canine and Feline, Seventh Edition  1535
◦ Contact of the catheter tip with 
pericardium may impart a scratchy 
sensation, which may alarm inexperienced 
◦ There may be a sensation of popping 
through the pericardium with the catheter.
• When PE is aspirated or observed in the 
hub of the stylet, the stylet is advanced a 
short distance (2–4 mm) further, after 
which the nondominant hand advances the 
flexible catheter off the stylet into pericardial 
space:
◦ A distended pericardium may shrink 
substantially during procedure, which will 
cause the catheter tip to exit the pericardial 
space if it is not advanced sufficiently or 
too short.
• Once the stylet is withdrawn, extension 
tubing is attached directly to catheter hub, 
leading to a large syringe and interposed 
three-way stopcock operated by an assistant.• Aliquots from this initial syringe of PE 
should be placed into an EDTA tube for 
cytologic analysis, a tube without additive or 
culturette for culture, and a tube without 
additive to assess for clotting of the sample 
(to verify the catheter is not intracardiac).
• Verifying appropriate placement of catheter.
◦ Monitor sample for coagulation; most 
effusions (unless peracute) will be 
defibrinated, and will not clot, while a 
sample from ventricular lumen will clot.
◦ A small amount of presumptive PE (e.g., 
5–20 mL) can be removed while heart rate 
is observed. With tamponade, even a small 
decompression of the pericardial space can 
demonstrably decrease heart rate. A 
continual decrease in heart rate throughout 
the procedure is suggestive of correct 
catheter placement, whereas increasing heart 
rates should prompt operator to suspend 
aspiration and reevaluate catheter position.◦ The effusion PCV may be determined; it 
should be different from the peripheral blood, 
and supernatant is often xanthochromic.
• Once catheter positioning within the 
pericardium is confirmed, PE can be 
evacuated rapidly using the three-way 
stopcock to alternately aspirate and expel PE 
into a collecting bowl.
• The pericardial space should be evacuated 
as completely as possible (exceptions are atrial 
tears and bleeding disorder).
• Other considerations:
◦ At any time during the procedure, 
significant ventricular arrhythmias should 
prompt catheter repositioning (usually 
partial withdrawal) and consideration of 
treatment with lidocaine (2 mg/kg IV) if 
arrhythmia does not abate promptly.
◦ A scratchy sensation may be transmitted 
to the catheter as it rubs against the 
pericardium and epicardium, or stuttering 
Figure 1 .
Instrumentation used for PC. A no. 11 blade is ideal for creating a small stab 
incision into the skin at the entry site. A 14-gauge, 5.25-inch catheter and 
stylus are shown with a small syringe attached; i.e., configured to advance 
into the pericardial space. Extension tubing, three-way stopcock, and 
syringes for aspiration are shown. The sharp metal stylus is removed after the 
catheter is fully positioned, and the catheter is attached to the extension 
tubing. Three prepared and labeled doses of 2% lidocaine for IV bolus 
(2 mg/kg = 1 mL/10 kg) are shown.(continued)  Pericardiocentesis

1536  Blackwell’s Five-Minute Veterinary Consult  
of the extension tubing caused by 
intermittent flow obstruction as the volume 
of PE decreases; at this point, the operator 
may slowly withdraw the catheter while the 
assistant maintains a small amount of 
suction with the syringe. Catheter 
withdrawal is paused at any location that 
results in additional aspiration of PE, and 
the process is repeated until catheter is 
completely withdrawn.
◦ Catheter tip should be inspected to verify 
that it is intact after removal.
◦ Cardiac motion may continue to expel 
PE into pleural space through catheter hole; 
this may result in lower than anticipated 
volumes of removed PE as well as pleural 
effusion following the procedure (there is 
no need to remove the pleural effusion).
• Pericardial fluid is placed in EDTA for 
cytologic examination and then in suitable 
sterile transport media for microbiological 
evaluation (bacterial and/or fungal).
• The hematocrit of presumed PE may be 
determined during the procedure, as noted 
above.
• Patients should be monitored for 12–24 
hours. Monitoring should include serial heart and respiratory rates, cardiac ultrasounds (to 
evaluate return of PE), and ECG.
• Significant ventricular arrhythmias may 
develop.
• Iatrogenic pneumothorax is possible.
• Return of PE and clinical signs may be 
rapid.
None specific to PC. Other care may depend 
on cause of PE.
N/A
• Ancillary medical treatments depend on the 
cause of the PE (e.g., neoplastic, infectious, 
• Abdominal effusion stemming from 
tamponade-induced CHF typically does 
not require diuretics or treatments other 
than PC.
• Fluid therapy if hemorrhagic or third space 
fluid losses cause hypovolemia.
Judicious exercise restriction.
PC typically produces dramatic and immediate 
improvement in hemodynamic parameters. 
However, dogs may remain subdued for 
1–2 days.  INTERPRETATION
N/A
• Cytologic evaluation of PE is notoriously 
nondiagnostic:
◦ Most common causes of PE (neoplasia 
and idiopathic)—typically produce hemorr -
hagic effusions without identifiable cell 
types or features that identify causative 
◦ Unusual causes of PE that may be 
diagnosed cytologically include lymphoma, 
unusual tumors, and bacterial or fungal 
• An increasing heart rate or clotting PE 
sample during PC. Do not aspirate further. 
Check to ensure correct catheter placement.
• Ventricular tachycardia (>180 bpm) or 
complex ventricular arrhythmia. Reposition 
(partially withdraw) the catheter and 
administer lidocaine (2 mg/kg IV).
None
Figure 2.
Catheter positioning and orientation for PC from the right ventral approach. 
While stabilizing the catheter near the entry point with the nondominant 
hand, the catheter is advanced cranially and dorsally with the dominant hand, 
i.e., toward the opposite scapula. A small degree of suction is maintained with 
the syringe so that pericardial fluid is aspirated at the moment of pericardial 
penetration. Subsequently, the syringe and stylet are held in stationary while 
the flexible catheter is advanced well into the pericardial sac. The sharp metal 
stylet is withdrawn after the catheter is fully positioned, and the catheter is 
then attached to extension tubing leading to a three-way stopcock and 
aspiration syringe.Pericardiocentesis  (continued)

Canine and Feline, Seventh Edition  1537
With Performing the Procedure
• A small (insufficient) volume of PE.
None
Species
Cats and small dogs may be more difficult for 
PC because of their small size.
Breed
N/A
Age
N/A
Sex
N/A
Pregnancy
N/A
• Rapid IV fluid administration should be 
administered to debilitated patients during 
preparation for PC.
• Complications are minimized by careful 
• Significant clinical improvement can occur 
with removal of even a small volume of 
effusion.• Hemodynamically significant PE requires 
PC to stabilize the patient.
• Echocardiography may provide a definitive 
diagnosis if an intrapericardial, right atrial, or 
heart base mass is present.
• Cytologic and microbiological examination 
of the PE.
• Further evaluation may include CBC and 
biochemical analysis, coagulation testing, 
toxoplasma titer (cats), thoracic radiographs 
and abdominal ultrasound in search of 
primary or metastatic neoplasia, histopathology, 
and thoracic exploration or thorascopic 
surgery for partial or complete pericardiectomy.
• In dogs with PE, elevation of plasma 
cardiac troponin I suggests an increased 
probability of hemangiosarcoma.
SEE ALSO
• Hemangiosarcoma, Spleen and Liver.
• Myocardial tumors.
• Rodenticide Toxicosis—Anticoagulants.SYNONYMS
Pericardial tap.
• PC = pericardiocentesis.
• PE = pericardial effusion.
MacDonald K. Pericardial diseases. In: 
Louis, MO: Saunders Elsevier, 2017, pp. 
1305–1316.
Nelson LO, Wendy AW. Pericardial effusion. 
In: Bonagura J, ed., Kirk’s Current 
Veterinary Therapy XV. Philadelphia, PA: 
WB Saunders, 2014, pp. 816–823.
Sisson D, Thomas WP . Pericardial disease and 
cardiac tumors. In: Fox PR, Sisson D, 
Moise NS, eds., Textbook of Canine and 
Feline Cardiology, 2nd ed. Philadelphia, 
PA: WB Saunders, 1999, pp. 400–425.
Author  Rebecca M. Bates
Consulting Editor  Benjamin M. Brainard(continued)  Pericardiocentesis

1538  Blackwell’s Five-Minute Veterinary Consult  
Point of Care Abdominal Ultrasonography
  BASICS
Point of care ultrasound.
• Abdominal veterinary point of care 
ultrasound (VPOCUS) is an expansion of the 
original abdominal-focused assessment with 
sonography for trauma (A-FAST®) protocol 
published in 2004: a limited or focused 
technique that can be performed by 
nonspecialists to rapidly assess patients and 
help direct immediate diagnostic and 
therapeutic interventions.
• It requires minimal training, is performed 
during triage or during daily patient 
evaluation, does not compromise patient 
safety, is noninvasive, rapid, repeatable, and 
• Abdominal VPOCUS has been validated 
for both trauma and nontrauma patients, and 
is sensitive and specific for the detection of 
free abdominal fluid:
◦ Mistakes are less likely, and learning is 
often facilitated, by asking simple binary 
questions (i.e., presence of free fluid yes/no).
◦ Additional binary questions (beyond the 
detection of free fluid) that have been 
evaluated with abdominal VPOCUS 
include assessment of gastrointestinal (GI) 
motility, estimation of urine production, 
identification of gall bladder wall edema/
thickening, and the detection of free 
abdominal air.
• T rauma patients.
• Unstable patients.
• Any patient as part of the triage exam.
• Post-surgery patients not recovering as 
expected.
• Routine daily assessment of hospitalized 
patients.
• To identify free abdominal fluid of any 
cause.
• Suspicion of pneumoperitoneum.
• Concern for adequate urine production.
• Suspicion of gastric retention or GI ileus.
None
None
Abdominal VPOCUS is not a full ultrasono-
graphic examination and does not replace 
comprehensive formal sonography, physical 
examination, or other diagnostic procedures, 
including radiographs. They are limited 
exams that answer specific questions in a very rapid fashion, often dictating the need for 
immediate therapy and further diagnostics, 
including comprehensive formal ultrasound 
examinations.
Focused areas of the abdominal cavity to 
answer specific, often binary, questions.
  PROCEDURE
• Do not compromise patient safety: bring 
the ultrasound machine to the patient and 
complete/continue any emergency 
stabilization and concurrent diagnostic 
efforts.
• Clipping of fur is unnecessary, although 
image quality may be improved with 
clipping.
Minimal restraint required, sedation rarely 
• Left or right lateral recumbency. The 
patient can be rolled into sternal recumbency 
to assess the gravity dependent paralumbar 
region if necessary, once the other sites have 
been evaluated.
• Sternal or standing if lateral not possible.
• Consider gravitational effects and patient 
positioning for different pathologies (e.g., free 
fluid).
• Avoid dorsal recumbency in patients with 
respiratory or cardiovascular compromise.
Serial VPOCUS monitors progression or 
resolution of underlying pathology.
• Ultrasound machine.
• Microconvex/curvilinear probe.
• Frequency: 5 MHz (patients >15 kg), 7.5 
MHz (patients <15 kg).
• Gain adjusted to detect anechoic fluid.
• Depth adjusted to visualize the region of 
interest.
• Coupling agent: 70% isopropyl alcohol, 
part fur before applying. Ultrasound gel can 
also be used.
TECHNIQUE
• Five focused regions of the abdomen are 
systematically evaluated: subxiphoid (also 
called diaphragmatico-hepatic), urinary 
bladder (also called cysto-colic), right 
paralumbar (also called hepato-renal), left 
paralumbar (also called spleno-renal), and 
umbilical (see Figure 1).• Fan and rock the probe through 45° angles in 
both longitudinal and transverse axis at all sites.
Key Structures
Key structures assessed at each site include:
• Subxiphoid: diaphragm, liver, gallbladder, 
ventral stomach, and the areas between these 
structures. The caudal vena cava, pleural 
space, and pericardial sac can also be 
evaluated at this site (not discussed in this 
chapter).
• Urinary bladder: urinary bladder, gravity 
and non-gravity-dependent body walls, and 
the areas between these structures.
• Right paralumbar: right caudal liver lobe, 
right kidney, body wall, duodenum, and the 
areas between these structures.
• Left paralumbar: spleen, left kidney, 
intestines, body wall and the areas between 
these structures.
• Umbilical (additional 5th view): gravity-
dependent body wall, intestines, spleen and 
regions between these structures.
Correctly Locating and Evaluating Each 
Site
Subxiphoid
• Palpate the “V” at the xiphoid region and 
place the probe in long axis to the body.
• Rock the probe cranially until the liver is 
visible.
• Adjust depth to visualize the diaphragm 
beyond the liver.
• Fan the probe through all planes of the liver 
and rock the probe to assess the most ventral 
and cranial parts of the liver (small fluid 
accumulations often collect between the liver 
and diaphragm).
• The gallbladder is visualized to the right of 
midline and assessed for wall thickening or 
other abnormalities.
• By rocking the probe perpendicular to the 
spine and slowly fanning left and right the 
proximal stomach wall is identified and can 
be assessed for motility.
• The probe is then rotated into transverse 
axis and fanned and rocked through all 
planes.
• The probe is placed in longitudinal axis to 
the body between the pelvic limbs.
• Pushing too hard can compress and displace 
the bladder.
• Adjust the depth to visualize both the dorsal 
and ventral bladder walls.
• Slide the probe to the non-gravity-depend-
ent side of patient and angle the ultrasound 
beam through the bladder, while fanning, to 
identify fluid in deeper gravity-dependent 
sites along the body wall.
• Slide the probe cranially to locate the apex 
of the bladder and fan the probe through all 
planes at the bladder apex.

Canine and Feline, Seventh Edition  1539
• Slide caudally to evaluate the caudal 
regions.
• Following thorough longitudinal scanning, 
rotate the probe to a transverse axis and 
repeat the scan.
• Bladder volume can be estimated in 
millimeters and monitored serially using the 
formula to calculate the volume of a sphere:
◦ In longitudinal axis, a measurement of 
the length is taken. This is L. A depth 
measurement in longitudinal can be taken 
(DL).
◦ In transverse axis, a width measurement 
is taken. This is W. A depth measurement 
in transverse can be taken ( DT).
◦ The formula is then as follows: ( L × W × 
(DL + DT)/2) × 0.625.
Right Paralumbar
• In smaller patients, the probe is placed in 
longitudinal axis to the body caudal to the 
last rib, just below the hypaxial/lumbar 
muscles.
• It may be necessary to place the probe 
between ribs to locate target structures.
• In dogs, if the liver is visualized first, the 
probe can be slid caudally until the kidney is 
located.
• The right kidney is often quite lateral 
(relative to midline).
• The probe is fanned and rocked in both 
longitudinal and transverse axis to assess the 
kidney.
• To locate the duodenum, place the probe at 
the level of the right kidney in longitudinal 
axis, and sweep medially towards midline until the largest small intestinal segment is 
found, which can be assessed for motility.
Left Paralumbar
• The probe is placed relatively lateral to 
midline to find the left kidney and spleen.
• The spleen is located cranial and often 
lateral to the left kidney.
• To find the left kidney, use your index 
finger to trace the last rib from the mid-
abdominal region dorsally: the kidney is 
usually located where the last rib encounters 
the hypaxial muscles.
kidney.
• It may be easier to find the spleen and slide the 
probe caudally until the left kidney is located.
Umbilical View
• The probe is placed over the umbilical 
region and directed towards the tabletop.
• The probe is then rocked and fanned 
through all planes and then changed from a 
longitudinal to transverse orientation and the 
procedure repeated.
• This allows localization of gravity-
dependent abdominal effusion to be 
identified before the probe is slid under the 
patient to assess the gravity-dependent 
paralumbar site.
Serial examinations are useful to detect 
changes in patient pathology: frequency is 
dictated by changes to patient stability (heart rate, respiratory changes, or neurologic 
changes).
• Free fluid appears as dark (anechoic or 
hypoechoic) uncontained triangles/sharp angles 
between organs and structures; be sure to 
thoroughly evaluate all key organs at all sites.
• Obtain fluid samples for in-house analysis 
(cytology, refractometer, parameters of sepsis 
or uroabdomen) which may dictate immedi-
ate interventions (surgery, antibiotics, trans  - 
fusion, etc.). Consider sample submission to 
reference laboratory (cytology, culture) if 
• Pneumoperitoneum in patients that have 
not undergone laparotomy is abnormal and 
hollow organ rupture should be ruled out. 
There are three key steps to help detect 
pneumoperitoneum:
◦ Identify the peritoneal lining; this helps 
differentiate GI air from free air in the 
abdomen. Place the animal in lateral for a 
few minutes to allow air to rise to the 
non-gravity-dependent body wall. The 
peritoneal lining can be visualized directly 
or identified by locating structures in 
contact with it (e.g., liver, kidney, spleen, 
etc.). Free air can be detected between 
organs or within the wall of some structures, 
although this is more technically challenging.
152 34
Figure 1 .
Abdominal VPOCUS windows: (1) subxiphoid, (2) umbilical, (3) urinary bladder, (4) left 
paralumbar, and (5) right paralumbar. Each location is evaluated in longitudinal and transverse 
orientation with rocking and fanning of the probe to maximize the area evaluated and to ensure 
all target structures/sites are thoroughly evaluated. At the urinary bladder and umbilical sites 
the probe should be directed toward the gravity-dependent body wall areas where fluid is most 
likely to accumulate.(continued)  Point of Care Abdominal Ultrasonography

1540  Blackwell’s Five-Minute Veterinary Consult  
◦ Identify the presence of reverberation 
artifact that originates at the peritoneal 
lining. This helps differentiates reverber -
ation artifact contained within the GI tract. 
Free air reverberation artifact originating at 
the peritoneal lining often obliterates 
structures below it.
◦ Identify the enhanced peritoneal stripe 
sign. This sonographic finding occurs when 
free abdominal air comes in contact with 
the peritoneal lining, causing the peritoneal 
lining to become more hyperechoic. Reverb -
eration artifact, if it is the result of free 
abdominal air, will originate from the 
enhanced peritoneal stripe sign.
• Ileus: Ileus is defined as a transient cessation 
of GI motility or an abnormal pattern of GI 
motility. The mean number of peristaltic 
contractions of the stomach and proximal 
duodenum are 4–5 contractions per minute. 
To measure the number of contractions per 
minute the total number of contractions is 
recorded over 3 minutes and divide by 3. If 
contractions are decreased to absent a 
diagnosis of decreased motility is made.
• Food within the GI tract is a strong 
stimulus for contraction; ileus is confirmed 
when food is present within the GI lumen in 
the absence of GI contractions.
• Gall bladder wall thickening/edema (halo 
sign) is not specific but anaphylaxis, fluid 
overload, right-sided heart failure, sepsis, and 
pericardial effusion should be considered in 
unstable patients.• Oliguria/anuria: Although not 100% 
accurate, a lack of change in bladder volume 
despite appropriate IV fluid in a well-hydrated 
patient could be indicative of anuria or oliguria.
• Dehydration and hypovolemia may reduce 
the sensitivity of finding abdominal effusion; 
reassess once resuscitation procedures are 
undertaken.
• Gas-filled GI tract can obscure some 
• Empty or very distended bladders may be 
difficult to interpret.
Species
Large-breed dogs may be more difficult to 
image due to the depth and location of their 
organs.
Age
Very young healthy animals may normally 
have small quantities of free fluid present.
• Abdominal VPOCUS is a rapid, repeatable 
diagnostic tool that helps identify specific 
• Requires minimal training or experience.  MISCELLANEOUS
SYNONYMS
Abdominal-focused assessment with 
sonography in trauma/triage (A-FAST®)
• VPOCUS = veterinary point of care 
Faculty of Veterinary Medicine, University of 
Calgary (UCVM) podcasts: https://vet.
ucalgary.ca/vcds/podcasts
ultrasound for dogs and cats in the 
emergency room: AFAST and TFAST. Vet 
Clin North Am Small Anim Pract 2013, 
43(4):773–797.
McMurray J, Boysen SR, Chalhoub S. 
Focused assessment with sonography for 
triage in non-trauma dogs and cats in the 
emergency and critical care setting. J Vet 
26(1):64–73.
Authors  Søren Boysen and Serge Chalhoub
acknowledge the prior contribution of Jantina 
McMurray.Point of Care Abdominal Ultrasonography  (continued)

Canine and Feline, Seventh Edition  1541
Point of Care Pleural Space and Lung Ultrasonography
  BASICS
Point of care ultrasound
• Pleural space and lung ultrasound (PLUS) 
is an expansion of thoracic focused assessment 
with sonography for trauma that includes 
lung ultrasound. Cardiovascular ultrasound is 
assessed separately as it involves the evaluation 
of both the abdomen (vascular) and heart 
(limited echocardiography):
◦ Pathologies evaluated include pleural 
effusion, pneumothorax, alveolar interstitial 
syndrome (AIS), and lung consolidation.
◦ A focused veterinary point of care 
ultrasound (VPOCUS) technique that can 
be performed by nonspecialists to rapidly 
assess patients and direct immediate 
diagnostic and therapeutic interventions.
▪ Requires minimal training, is 
performed during triage or daily patient 
safety, is noninvasive, rapid, repeatable, 
and objective.
▪ Accuracy is variable, and depends on 
the experience of the sonographer, 
underlying pathology, patient positioning, 
scanning protocol, and criteria used to 
identify the different pathologies.
◦ In the authors’ experience the most 
common clinical errors include failing to 
identify pneumothorax by not scanning the 
most caudal dorsal sites, missing smaller 
volume pleural effusions by not scanning 
the more ventral regions when patients are 
in sternal or standing positions, and 
confusing the curtain sign for lung 
• Principles of PLUS that increase the chance 
of detecting pathology include the application 
of binary questions to keep scanners focused 
to techniques and questions within their skill 
sets, modifying protocols to evaluate areas of 
the pleura and lung where pathology is most 
likely to accumulate, and defining sonograph­
ically scannable thoracic borders:
◦ If pleural effusion needs to be ruled out 
in a standing patient, then searching the 
most ventral borders between the lung and 
sternal muscles (where fluid accumulates) is 
important vs. a patient that is lateral (where 
fluid will accumulate at the widest, most 
gravity ­dependent point of the thorax).
◦ In a patient with severe dyspnea, the 
binary question (based on initial triage 
examination) dictates which part of the 
PLUS protocol is performed first (e.g., 
pneumothorax, pleural effusion, lung pathology). Once the patient is more stable, 
completion of the PLUS examination and 
other VPOCUS scans can be performed.
◦ Defining sonographically scannable 
borders of the thorax on either side of the 
chest helps ensure sites where pathology are 
most likely to accumulate are evaluated.
• Dyspneic patients.
• Part of the triage exam.
• Post­surgery patients not recovering as 
expected.
• Routine daily assessment.
• Suspected pneumothorax.
• Suspected pleural effusion.
• Suspected alveolar interstitial disease.
None
None
PLUS is not a full ultrasonographic examination 
of the thorax and does not replace comprehensive 
formal sonography, physical examination, or 
other diagnostic procedures including thoracic 
radiographs. It is a focused exam that answers 
specific questions in a rapid fashion, often 
dictating the need for immediate therapy and 
further diagnostics, including comprehensive 
formal ultrasound examinations.
Lungs and pleural space to answer specific 
questions.
  PROCEDURE
continue emergency stabilization and 
concurrent diagnostic efforts.
• Clipping of fur is unnecessary but may 
improve image quality.
• Minimal restraint required.
• Oxygen therapy and anxiolytics may calm 
patients, decreasing the respiratory rate and 
effort, making interpretation easier.
• Air accumulates at the highest gravity ­
independent areas; fluid at the most gravity ­ 
dependent areas, which varies with patient 
• Dyspneic patients should be scanned in sternal/standing to avoid stress.
• More stable patients can be scanned in left 
or right lateral recumbency.
• Avoid dorsal recumbency in dyspneic or 
cardiovascularly compromised patients.
• Frequency adjusted to make the pleural line 
appear grainy when assessing the glide sign 
(typically 5–7.5 mHz).
• Depth adjusted to 4–6 cm; pleural line 
should be located at roughly a third the 
distance of the ultrasound image.
• Coupling agent; alcohol, part fur before 
applying. Ultrasound gel can also be used.
TECHNIQUE
The following PLUS protocol has three 
objectives: assess for (1) pneumothorax, (2) 
lung pathology, and (3) pleural effusion. The 
order can be modified to rule out the most 
likely and life ­threatening pathology first. It is 
intended for the sternal/standing patient. 
(The protocol is slightly modified when 
searching for pleural effusion and/or pneumo­
thorax in laterally recumbent patients; see 
below.)
1. Place the probe on a region of the thorax 
where lung can be reliably identified, behind 
the thoracic limb, roughly between the 5th–6th 
intercostal space and half to two ­thirds of the 
way up the thorax (see Figure 1). Starting at 
this location avoids accidental placement of 
the probe over the curtain sign, abdomen and 
sublumbar muscles, which can be confused for 
pathology. The probe can be placed perpendicular 
or parallel to the ribs. For beginners, the 
authors recommend placing the probe 
perpendicular to identify the BAT sign.
2. Normal structures are identified at this 
location (see Normal Findings or Range: BAT 
sign, pleural line, glide sign, A ­lines, B ­lines, 
curtain sign).
3. If a glide sign is seen, slide the probe 
caudally until the curtain sign is identified:
• Patients with significant pneumothorax 
will not have a glide sign at this location 
and thoracentesis or a search for the lung 
point should be undertaken (see Abnormal 
Findings).
4. From the curtain sign, slide the probe 
dorsocaudally along the curtain sign until the 
hypaxial muscle–pleural space junction is 
identified. This is the most caudo ­dorsal site 
of the thorax and the smaller volumes of 
pneumothorax are likely to be identified in a 
standing/sternal patient (see below):

1542  Blackwell’s Five-Minute Veterinary Consult  
• If a glide sign is seen here, pneumotho­
rax is ruled out for this side of the thorax 
in the standing/sternal patient.
• If a glide sign is not seen here, and a 
pneumothorax cannot be ruled out based 
on clinical findings, then search for a lung 
point or return of the glide sign (see below).5. If a glide sign was identified in step 4, and 
pneumothorax ruled out, continue scanning 
for lung pathology (AIS and lung consolidation) 
and pleural effusion; for AIS/lung consolida­
tion slide the probe across the intercostal 
spaces in an “S” fashion to scan multiple lung 
regions. Pause and hold the probe stationary as necessary to better assess suspected areas 
for pathology:
• From the most caudo ­dorsal position, 
slide the probe across the dorsal border of 
the thorax as cranial as possible to the 
scapula/flexor muscles of the shoulder (a)
Figure 1a.
The probe is placed over lung, then slid caudally until the curtain sign is identified (caudal 
lung border). Then slide dorsally along the curtain sign, focusing on the pleural line, until 
the pleural line is lost in the hypaxial muscles. Return to the pleural line. This is the most 
caudal dorsal site, which can be rapidly identified with confidence in any patient. Source: 
From Boysen S, McMurray J and Gommeren K (2019) Abnormal Curtain Signs Identified 
With a Novel Lung Ultrasound Protocol in Six Dogs With Pneumothorax. Front. Vet. Sci. 
6:291. doi: 10.3389/fvets.2019.00291. Public Domain.Point of Care Pleural Space and Lung Ultrasonography  (continued)
(b)
Figure 1b.
From the most caudal dorsal site, slide the probe in an “S” ­shaped pattern, dividing the 
thorax into dorsal, middle, and ventral thirds to assess multiple lung regions for pathology. 
Source: From Boysen S, McMurray J and Gommeren K (2019) Abnormal Curtain Signs 
Identified With a Novel Lung Ultrasound Protocol in Six Dogs With Pneumothorax. 
Front. Vet. Sci. 6:291. doi: 10.3389/fvets.2019.00291. Public Domain.

Canine and Feline, Seventh Edition  1543
while continuing to visualize the pleural 
line for pathology:
• Once the cranial–dorsal border is 
reached, slide the probe ventrally to the 
mid­thorax, roughly at the heart base 
region, and then caudally toward the 
curtain sign while continuing to visualize 
the pleural line for pathology.
• At the curtain sign, slide the probe 
ventrally until the pericardio ­diaphrag­
matic window is identified (where the 
heart and diaphragm are visible in the 
same sonographic window). This is a good 
window to differentiate pleural and peri ­ 
cardial fluid.
• The probe is then slid cranially until the 
thoracic inlet is reached (limited by the 
thoracic limb).
• To avoid missing smaller volumes of 
pleural effusion turn the probe parallel to 
the ribs at or just below the costochondral 
junction, roughly between the 3rd and 7th 
intercostal spaces, and slide the probe 
ventrally until the lung and sternal muscle 
are both visible in the same sonographic 
window. To also assess the ventral lung 
borders for pathology, the probe can be 
slid dorsally from the sternal–pleural 
junction, between the ribs at these same 
intercostal spaces (maintaining the probe 
parallel to the ribs), until lung is 
encountered.6. The other side of the thorax should be 
scanned in a similar fashion.
7. The subxiphoid should also be included 
for assessment of pleural effusion and AIS/
lung consolidation:
• The probe can be placed in long and 
short axis to the body in the subxiphoid 
region. Palpate the “V” where the ribs 
connect ventrally and place the probe at 
this location. The probe is then rocked 
and fanned so that the ultrasound beams 
penetrate the thorax.
• Once the thorax is visualized, the probe 
is fanned to visualize the entire region.
8. With the patient in lateral recumbency the 
protocol is similar, however it should be 
remembered that fluid will accumulate at the 
widest gravity ­dependent location of the 
thorax and air will accumulate at the widest 
most non ­gravity ­dependent location. These 
sites should be considered and the protocol 
modified in light of patient positioning, the 
binary question to answer first, and the 
pathology in question.
Serial thoracic VPOCUS examinations are 
useful to follow resolution/progression of 
pathology, and should be repeated as dictated 
by changes to patient stability.  INTERPRETATION
Normal Structures
There are six key PLUS findings to identify in 
healthy animals, which should also be 
assessed in animals with suspected pathology.
1. BAT Sign (also termed the gator sign) 
(see Figure 2)
Using the BAT sign mnemonic—“the 
ultrasound beam will not traverse Bone or Air 
when the probe is T ransverse to the ribs”—
helps sonographers to orient.
• The ultrasound beam will not traverse 
beyond the proximal rib surface (smaller 
downward facing curvilinear white lines) or 
the pleural line (upward curving white line) 
in healthy animals, which means these 
structures are the last visible features the 
ultrasound beam can identify when the 
ultrasound probe is situated over lung and 
oriented perpendicular to the ribs: everything 
beyond the ribs and pleural line is artifact in 
healthy animals.
• The pleural line is essential to identify as all 
PLUS pathology originates from the pleural 
line: the first horizontal white line below the 
ribs that connects the rib shadows (body of 
the bat).(continued)  Point of Care Pleural Space and Lung Ultrasonography 
(c)
Figure 1c.
At the ventral regions of the thorax (level of the costochondral junction) the probe can be 
turned parallel to the ribs and slid ventrally until the sternal muscles are encountered. This 
ensures small volumes of pleural fluid that may not be seen with the probe perpendicular 
to the ribs at the level of the costochondral junction are not missed. From the sternal 
muscles, which are often in contact with the heart in the 4th–6th intercostal spaces, the 
probe can also be slid dorsally to ensure the ventral lung regions are assessed for pathology. 

1544  Blackwell’s Five-Minute Veterinary Consult  
2. Pleural Line
When the lung is in contact with the chest 
wall the pleural line indicates the parietal 
pleura and the visceral pleura are joined. In 
cases of pneumothorax or pleural effusion, 
the pleural line comprises only the parietal 
pleura (the visceral pleural is visible deep to 
pleural effusion and not visible with pneumo ­ 
thorax).
• All pleural space pathology (i.e., pleural 
effusion, pneumothorax, etc.) originates at 
the pleural line.
• All sonographically detectable lung pathology 
originates at the visceral pleura (lung surface), 
which will be at the pleural line when lung 
contacts the chest wall, and the visceral pleura 
when the lung is visibly separated from the 
chest wall (e.g., pleural effusion).
3. The Glide Sign
The to ­and­fro shimmering visible along the 
pleural line that occurs as a result of lung 
sliding along the chest well during the 
respiratory cycle:
• The glide sign rules out pleural space 
pathology, particularly pneumothorax and 
• T wo criteria must be present for a glide sign 
to occur: (1) the two pleura must be in 
contact; (2) the patient must breathe for the 
two pleura to glide across each other creating 
the visible shimmering.
• The glide sign can be made “grainier” and 
therefore easier to visualize by changing the angle the ultrasound beam strikes the pleural 
line (changing the angle from perpendicular), 
by placing the probe over a single rib head, 
and by decreasing the gain setting.
• The glide sign is difficult to identify in 
patients that are panting or have rapid 
shallow breathing.
• Keep your hand stationary and only interpret 
the glide sign when the patient is not moving 
(movement creates a false positive).
4. A-Lines
Horizontal white line artifacts occurring at 
equidistant intervals that project through the 
far field of the ultrasound image, decreasing 
in intensity with depth.
• A­lines are created when the ultrasound 
beam is bounced back and forth between the 
ultrasound probe and highly reflective 
structures such as the soft tissue–air interface 
that occurs at the pleural line.
• A soft tissue–air interface is present at the 
pleural line when air fills the lung and when 
air occupies the pleural space in cases of 
pneumothorax. Therefore A ­lines are visible 
with both aerated lung and pneumothorax.
5. B-Lines (Figure 3)
Vertical white line artifacts that occur when 
air and fluid are in proximity to each other at 
the lung surface.
• They often have the following five criteria: 
(1) vertical white/hyperechoic projections; (2) 
originating from the lung surface at the pleural line; (3) extending through the far 
field without fading; (4) obliterating A ­lines if 
present; and (5) swinging to ­and­fro with the 
glide sign during respiration.
• Up to three B ­lines in a single sonographic 
window, but only at 1 or two locations on 
either side of the thorax is considered normal 
and may be identified in 10–30% of healthy 
• More than three B ­lines at a single site is 
associated with AIS/wet lung.
• The same differential diagnosis for AIS on 
ultrasound should be considered as an 
interstitial–alveolar pattern on thoracic 
• The number of B ­lines correlates with the 
quantity of extravascular lung water, although 
prognosis varies with cause.
6. Curtain Sign
Sharply demarcated vertical edge artifact 
separating aerated lung from abdominal 
contents, (thoraco ­abdominal border) (see 
Figure 4).
• When the ultrasound probe is positioned 
such that it is over both the thorax and the 
abdomen with the marker of the probe 
directed cranially, the cranial half of the image 
(thorax) will not allow the ultrasound beam 
to extend past the pleural line (produces 
A­lines), while the caudal half of the image 
(abdomen) allows the beam to be transmitted 
through the far field, permitting soft tissue 
structures to be visible.Point of Care Pleural Space and Lung Ultrasonography  (continued) 
Figure 2.
Image depicting the BAT sign where the ultrasound beam encounters Bone (rib heads = wings of the bat) and Air (pleural line = body of the bat) with the probe T ransverse 
(perpendicular) to the ribs. Horizontal A ­lines are also shown.

Canine and Feline, Seventh Edition  1545
• During inspiration, the vertical edge and 
abdominal contents move caudally, and 
during expiration the vertical edge and 
abdominal contents move cranially, in a 
synchronous manner.
• It is important not to confuse the curtain 
sign (back and forth movement of the 
diaphragm) with a glide sign.
Dry Lung
Dry lung at a probe location is identified 
when the following two criteria are present:
• The patient has a glide sign.
• There are ≤three B ­lines in a single 
sonographic window, and/or the presence of 
only A ­lines (not always visible).ABNORMAL FINDINGS
• There are three key findings in deciding if a 
pneumothorax is present or not; two are 
exclusion criteria, one is an inclusion criteria:
◦ The presence of a glide sign rules out 
pneumothorax at the probe location with 
confidence. Lack of a glide sign should 
prompt consideration of pneumothorax, 
but a glide sign is not always easy to 
identify, even in healthy patients.
◦ The presence of B ­lines extending from 
the pleural line excludes pneumothorax at 
that probe location because B ­lines 
originate from the lung surface. B ­lines are not always visible in healthy patients.
◦ Finding a lung point or the return of a 
glide sign confirms pneumothorax on that 
side of the thorax. If a glide sign is not seen 
and there is suspicion of a pneumothorax a 
search for the lung point should be 
• The lung point is defined as the site within 
the thorax where the lung recontacts the 
parietal pleura and creates an intermittent or 
partial glide sign within a section of the 
ultrasound image when the patient breathes. It 
is the exact point within the thorax where there 
is a return of the glide sign: movement of the 
probe from an area where there is no perceived 
glide sign, to an area where the glide sign (continued)  Point of Care Pleural Space and Lung Ultrasonography 
Figure 4.
Curtain sign, depicted as the sharp vertical line separating aerated lung from the soft tissue structures of the abdomen. The diaphragm is not visible once it curves away 
from the thoracic wall as interposed lung prevents its visualization.
Figure 3.
Images depicting a single B ­line (left), four B ­lines (middle), and multiple to coalescing B ­lines (right).

1546  Blackwell’s Five-Minute Veterinary Consult  
reappears within a region of the ultrasound 
window. Air in the pleural space (pneumotho ­
rax) tends to compress the lung cranially and 
ventrally: to identify the lung point slide the 
probe cranially–ventrally toward the elbow 
from the site where a glide sign was not visible. 
The lung point will not be seen if the lung fails 
to recontact the chest wall in cases of massive/
complete pneumothorax.
Pleural effusion appears as hypoechoic 
accumulations between the thoracic wall and 
lungs, and its appearance can vary depending 
on the cellularity of the effusion, probe 
location, patient positioning, the quantity of 
fluid and the presence of adhesions.
• Locating the pericardio ­diaphragmatic 
window helps differentiate pleural effusion 
from pericardial effusion; pleural effusion is 
uncontained outlining and tracking along the 
diaphragm while pericardial effusion is 
contained and curves away from the diaphragm 
following the contour of the heart.
• The presence of fluid between the lung and 
ventral sternal muscles, with the probe parallel 
to the ribs creates a triangular shape of 
anechoic fluid similar to a sail. (the “sail sign”).
• As fluid accumulates the lungs may become 
atelectatic, appearing as floating tissue ­like 
structures termed the “jellyfish” sign in 
human medicine.
AIS
Lung ultrasound will only detect lung 
pathology if it reaches the lung surface. Most 
diseases that cause AIS (cardiogenic 
pulmonary edema, trauma ­induced 
contusions, aspiration pneumonia, etc.) reach 
the lung surface. As stated above, three or 
more B ­lines in any single sonographic 
window is considered indicative of AIS.
Lung Consolidation
Sonographically detected lung consolidation 
can occur as a result of atelectasis, broncho­
pneumonia, thromboembolism, neoplasia, 
and inflammatory conditions such as 
pulmonary contusions and acute respiratory 
• Criteria to diagnose lung consolidation:
◦ Abnormal pattern should be differentiated 
from the liver, spleen and other soft tissue 
abdominal structures.
◦ Abnormal pattern should arise from the 
pleural line.
◦ There should be a tissue ­like pattern 
(similar to liver echotexture).
◦ Anatomic boundaries must be present:▪ Superficial boundary of consolidation.
▪ At the pleural line in the absence of 
▪ At the deep boundary of a pleural 
effusion if effusion present.
◦ Deep boundary of the consolidation may 
be irregular (aerated lung boundary) or 
regular (if the whole lobe is consolidated).
◦ When consolidation fails to traverse the 
entire lung lobe (partial consolidation) 
aerated lung is encountered deep to the 
consolidation which can create an irregular 
consolidation/air interface, called a “shred 
sign.” At the consolidation/aerated lung 
interface a hyperechoic irregular border is 
seen that usually creates comet tail artifacts.
◦ If the border between the consolidation 
and aerated lung is smooth and almost 
circular, it most likely represents a nodule.
◦ Where consolidation extends through the 
entirety of the lung, from one surface to the 
other, translobar hepatization is seen.
◦ Air bronchograms, if present, can be seen 
within lung consolidation as small white 
hyperechoic pointed foci or lines.
• Patient position affects where pathology 
may be found and is important to consider 
when scanning patients.
• Severe dehydration and hypovolemia may 
reduce the sensitivity of finding pleural effusion; 
patients should be reassessed with VPOCUS 
once resuscitation procedures are undertaken.
Large ­breed dogs may be more difficult to 
image, especially at the subxiphoid region due 
to the depth of their pleural surface.
• PLUS examinations are a quick and 
repeatable diagnostic tool that can help 
identify pathology and direct further 
diagnostics and therapy.
• VPOCUS examinations require little 
training and experience.
• Pericardiocentesis.SYNONYMS
TFAST®, VetBLUE®, lung ultrasound.
SEE ALSO
Point of Care Abdominal Ultrasonography 
(in Appendix X).
• AIS = alveolar interstitial syndrome.
• PLUS = pleural and lung ultrasound.
Armenise A, Boysen RS, Rudloff E, et al. 
Veterinary ­focused assessment with 
sonography for trauma ­airway, breathing, 
circulation, disability and exposure: a 
prospective observational study in 64 canine 
trauma patients. J Small Anim Pract 2019, 
60:173–182.
Boysen S, McMurray J, Gommeren K. 
Abnormal curtain signs identified with a 
novel lung ultrasound protocol in six dogs 
with pneumothorax. Front Vet Sci 2019, 
6:291.
Vezzosi T, Mannucci T, Pistoresi A, et al. 
Assessment of lung ultrasound B ­lines in 
dogs with different stages of chronic 
valvular heart disease. J Vet Intern Med 
2017, 31(3):700–704.
Walters A, O’Brien M, Selmic L, et al. 
Evaluation of the agreement between 
focused assessment with sonography in 
trauma (AFAST/TFAST) and computed 
tomography in dogs and cats with recent 
trauma. J Vet Emerg Crit Care 2018, 
28(5):429–435.
Ward JL, Lisciandro GR, Keene BW, et al. 
Accuracy of point ­of­care lung ultrasonog­
raphy for the diagnosis of cardiogenic 
pulmonary edema in dogs and cats with 
acute dyspnea. J Am Vet Med Assoc 2017, 
250(6):666–675.
McMurray.Point of Care Pleural Space and Lung Ultrasonography  (continued)

Canine and Feline, Seventh Edition  1547
  BASICS
• Quick, relatively noninvasive, technique 
that can be used to diagnose certain colonic 
or rectal diseases.
• Different from fecal cytologic evaluation, 
which looks for diversity of the fecal bacterial 
• Chronic or very severe large-bowel disease 
(especially patients with hypoalbuminemia, 
weight loss, or both) in dogs that may have 
fungal disease (e.g., histoplasmosis), algal 
disease (i.e., protothecosis), neoplastic disease, 
and especially those with mucosal abnorma -
lities on digital rectal palpation.
• Procedure is seldom indicated in cats.
Severe coagulopathy.
• Excessive bleeding (rare).
• Perforation if exceedingly improper 
technique is employed.
• Specific for certain infections but is 
insensitive—if the results are negative, you 
have not eliminated any diseases.
• It is appropriate to evaluate rectal cytology 
before performing endoscopy in dogs with 
suspected fungal, algal or neoplastic disease, 
especially if mucosal abnormalities are found 
on rectal examination.
  PROCEDURE
None
Sedation with narcotics/neuroleptanalgesics 
or anesthesia with injectable propofol may be 
needed in animals that are in excessive pain 
during the rectal examination.
May be performed with the patient in any of 
several positions.
None
• Examination gloves.• A small curette or similar instrument.
TECHNIQUE
• A gloved finger is inserted into the rectum, 
and a complete digital rectal examination is 
• Next, a small curette is guided into the 
rectum with the finger, and the rectal mucosa 
is gently scraped to obtain epithelial cells:
 ◦The goal is to obtain mucosal epithelium, 
not feces.
 ◦Blood should not be obvious after the 
• Spread epithelial cells on a glass slide, 
air-dry, and stain with new methylene blue, 
Diff-Quik, or modified Giemsa.
• In larger dogs, one may tape the cap of a 
syringe casing to the tip of the index finger 
and use it to scrape the rectal mucosa.
The slide is handled routinely as any cytologic 
slide.
None
None
None
None
None
Immediate
No fungal organisms, no algae, and no 
appreciable inflammation.
• Fungal organisms (e.g., histoplasmosis, 
typically found in macrophages).
• Algae (i.e., protothecosis).
• Substantial numbers of neutrophils or 
eosinophils.
• Malignant cells.
None
Excessive rectal or anal pain makes sedation 
or anesthesia necessary.Procedure Techniques or Handling That 
None
Species
This procedure is almost never performed in 
cats.
Breed
None
Age
None
Gender
None
Pregnancy
None
• Specific but not necessarily sensitive for 
diagnosis of colonic histoplasmosis, a disease 
that is common in select geographic areas of 
• May help diagnose severe colitis by finding 
substantial numbers of neutrophils, but this is 
a nonspecific finding that can occur in 
numerous disorders.
• Care must be taken before diagnosing a 
malignancy based solely on cytologic analysis 
because epithelial dysplastic changes are 
common in many diseases.
Colonoscopy and biopsy are required if rectal 
cytologic analysis is nonrevealing in a dog that 
is suspected of having colonic histoplasmosis, 
protothecosis, or rectal neoplasia.
SYNONYMS
Rectal scrape.
SEE ALSO
Histoplasmosis
Clinkenbeard KD, Cowell RL, Tyler RD. 
Disseminated histoplasmosis in dogs: 12 
cases (1981–1986). J Am Vet Med Assoc 
1988, 193:1443–1447.
Jergens AE, Andreasen CB, Hagemoser WA, 
et al. Cytologic examination of exfoliative 
specimens obtained during endoscopy for 
diagnosis of gastrointestinal tract disease in 
dogs and cats. J Am Vet Med Assoc 1998, 
213:1755–1759.
Consulting Editor  Benjamin M. BrainardRectal Scraping and Cytology

1548  Blackwell’s Five-Minute Veterinary Consult  
  BASICS
Whole blood (anticoagulated with  
EDTA).
• Performed when erythrocytes are aggregated 
(clusters of grapes) or stacked (similar to 
coins) on a blood smear. This finding 
indicates erythrocyte rouleaux or 
agglutination:
 ◦Rouleaux occurs due to interactions of 
red blood cells with plasma proteins such as 
 ◦Agglutination is caused by presence of 
antibodies (usually IgM) on surface of red 
cells, forming bridges between one another 
and spontaneously aggregating. Most 
commonly associated with immune-
mediated hemolytic anemia (IMHA).
• When saline agglutination test is 
performed, rouleaux will disperse in the 
presence of saline but agglutination  
will not.
Differentiate erythrocyte rouleaux from 
antibody-mediated agglutination.
None
None
Negative saline agglutination test does not 
rule out IMHA.
Hemic/immune.
  SAMPLE
One drop of whole blood and 4 drops of 
sterile 0.9% saline are required.
• Saline should be between 23 and 37°C; 
collect blood into EDTA and observe for 
agglutination on microscope slide.
Test should be interpreted immediately.
• EDTA-anticoagulated blood:
 ◦Several hours at room temperature.
 ◦1 day at 2–8°C (refrigerated).PROTOCOL
• There is no standardized protocol for this test.
• Add a drop of whole blood to a microscope 
slide.
• Dilute this drop of blood by adding four 
drops of saline.
• Rock slide gently back and forth before 
examining it macroscopically and micro -
scopically for agglutination. Cover slip 
recommended for microscopic evaluation.
• T rue agglutination will continue to form 
aggregates that appear similar to clusters of 
grapes in the presence of saline. Rouleaux will 
be dispersed by saline and no aggregation will 
be observed.
• Additional saline can be added if there is 
concern that an insufficient amount was 
added in order to rule out rouleaux.
• For inconclusive results, washing erythrocytes 
3 times in a 1:4 ratio is recommended to 
confirm persistent aggregation.
Lack of macroscopic or microscopic 
aggregation.
Persistent aggregation with addition of 
saline.
None
T reatment with corticosteroids may result in 
false-negative results.
• Animals occasionally have naturally 
occurring anti-erythrocyte antibodies, causing 
a positive result; however, these animals are 
not generally anemic and clinical history is 
important to differentiate normal from 
pathologic agglutination.
• Cold agglutinins may not precipitate at the 
temperature of test and result in false-negative 
result.
• Inadequate amount of saline may not 
disperse rouleaux (false positive).
• Overdilution with saline may cause 
dispersion of agglutination (false negative).
• Letting dilution sit for too long before 
interpretation may result in false-negative 
results if antibodies are of low affinity.Influence of Signalment
Species
Cats can exhibit more rouleaux in health than 
dogs; it is recommended to add more saline 
when performing this test in cats.
Breed
IMHA is more common in some dog breeds 
(e.g., cocker spaniels, English springer spaniels, 
Old English sheepdogs).
Age
None
Sex
None
Pregnancy
None
• Lack of standardized protocol makes 
interpretation and reproducibility 
• Cannot always differentiate between 
rouleaux and autoagglutination, particularly if 
antibodies causing agglutination are of low 
affinity and easily dispersed.
• Rouleaux and agglutination may be present 
at the same time.
Yes
• IMHA.
• Infectious disease.
• Toxicities (e.g., bee sting envenomation).
• Drug reaction.
• Alloimmune hemolytic anemia.
• Some clinical pathologists do not endorse 
this test due to lack of standardization of 
protocol and interpretation.
• Some cases of IMHA do not display 
macroscopic or microscopic agglutination.
• Not a standalone test for diagnosis of 
IMHA; requires proper interpretation of 
history, physical exam, complete blood count 
(CBC) with blood smear review, biochemical 
profile, ± Coombs’ testing.
A Coombs’ test is not indicated if saline 
agglutination is positive as it would be 
expected to be positive as well.
SYNONYMS
Saline dispersion test.Saline Agglutination Test

Canine and Feline, Seventh Edition  1549
SEE ALSO
anemia.
https://todaysveterinarypractice.com/
diagnosis-of-immune-mediated-hemolytic-
anemia/ Suggested Reading
Brazzell JL. The saline agglutination test—
why you might reconsider performing it. 
Marshfield Labs: Reference Point, 2016.
2019, 33:313–334.Harvey JW. Erythrocyte agglutination. In: 
Guide and Color Atlas. St. Louis, MO: 
W.B. Saunders, 2012, pp. 13–14.
Author  Alyssa J. Brooker
Consulting Editor  Benjamin M. Brainard(continued)  Saline Agglutination Test

1550  Blackwell’s Five-Minute Veterinary Consult  
  BASICS
• Thoracocentesis or pleurocentesis can be 
performed for one of two purposes: diagnostic 
evaluation or therapeutic intervention:
 ◦Diagnostic thoracocentesis can be 
essential for diagnosing the presence of 
pleural space disease and evaluating the 
contents of the cavity, whether air or 
fluid. Pleural fluid can then be further 
evaluated grossly for color and 
consistency, and microscopically for 
cellularity and the presence of protein or 
 ◦Therapeutic thoracocentesis is used to 
treat pleural effusion and pneumothorax 
resulting from a variety of causes. Typically, 
therapeutic thoracocentesis follows a 
positive diagnostic tap.
• When the presence of pleural air or fluid 
is suspected, especially in an animal with 
increased inspiratory effort and reduced 
breath sounds on thoracic auscultation.
• To sample/alleviate pleural air or fluid 
identified on an imaging study.
• Conditions leading to pleural space disease 
include trauma, hemorrhage, neoplasia, heart 
failure, chylothorax, spontaneous rupture of a 
pulmonary bulla, and infection.
Thoracocentesis should be performed cautiously 
on patients with abnormal hemostasis.
• Lung puncture or laceration producing 
pneumothorax. More likely to be serious in 
patients with pleural fibrosis.
• Hemorrhage, if the internal thoracic artery 
is lacerated.
• If the fenestrated catheter technique is used, 
and the fenestrations are not small and 
smooth, the catheter can get caught on the 
skin and break, with pieces remaining in the 
patient.
• Infection (pyothorax) can develop if sterile 
technique is not used.
Clients should be aware of the potential 
complications of the procedure and the 
potential severity of the underlying disease.
• Hemic, lymphatic, and immune.
• Respiratory.  PROCEDURE
• Sedation may be necessary, especially 
in cats.
• Clip the hair over a large area of the lateral 
thorax. The point of needle insertion should 
be at the 7th–9th intercostal space, dorsal to 
the costochondral arch.
• To remove fluid, the needle should enter at 
the level of the costochondral junction. To 
remove air, it should enter where the chest 
wall is widest.
• Local anesthetic is generally not necessary 
for a diagnostic tap. However, local anesthesia 
is imperative for therapeutic thoracocentesis. 
Lidocaine (no more than 2 mg/kg) should be 
injected SC and infused into the intercostal 
muscles.
• Scrub the skin surface with povidone-
iodine or chlorhexidine. Contact time should 
be at least 3 minutes and then wipe with 
alcohol.
• For emergency therapeutic thoracocentesis, 
full skin antisepsis may be abbreviated.
• Selection should be based on the individual 
patient.
• Often, butorphanol ± acepromazine or a 
benzodiazepine is sufficient.
• The patient should be in a comfortable 
position that does not compromise its 
respiration. Typically, the patient is in sternal 
recumbency or standing:
 ◦Sitting should be avoided because it 
interferes with accurate determination of 
landmarks.
• Supplemental oxygen may stabilize  
patient and improve comfort during  
centesis.
Respiration, heart rate, and pulse should be 
monitored throughout procedure.
Diagnostic T ap
• A 3-mL syringe with a 22-gauge, 1-inch 
needle can be used for cats and most dogs, for 
large (>30 kg) or obese dogs, a 1½-inch 
needle may be needed.
• A butterfly needle can also be used in cats 
and small dogs.
• Serum and EDTA tubes, and culture swabs 
needed for fluid analysis.
Therapeutic T ap
• A 14- to 16-gauge, 3½- to 5¼-inch catheter 
for dogs.• A 16- to 20-gauge, 2- to 3½-inch catheter 
for cats and small dogs or a butterfly needle.
• A 3-mL syringe.
• A 12- to 60-mL syringe.
• An IV fluid-extension set.
• A three-way stopcock.
• A container for fluid.
TECHNIQUE
Diagnostic Thoracocentesis
• Locate the desired point of insertion by 
counting to the 7th–9th intercostal space. 
Begin counting in the caudal most intercostal 
space (12th space) and count cranially. 
Position the needle at the widest point of the 
thorax for air, and just dorsal to the costo -
chondral arch for aspiration of fluid.
• Stabilize both hands on the animal so that 
the hands and the needle move with the chest 
wall. Insert the needle through the skin at the 
cranial aspect of the rib; once in the subcutaneous 
space, apply 1–2 mL of vacuum on the syringe. 
Slowly advance the needle perpendicular to 
the body wall while maintaining vacuum. 
Penetration of the pleura is indicated when 
the vacuum is suddenly lost (pneumothorax) 
or fluid enters the syringe (effusion):
 ◦Penetration of the pleura may cause 
discomfort to the patient, and should be 
palpated by the operator as a slight pop.
• Once the presence of pleural fluid or air is 
confirmed, withdraw the needle slightly to 
decrease the likelihood of lung laceration.
Butterfly Catheter Technique
• For diagnostic or therapeutic 
• When using this technique, position the 
needle so that the bevel is facing cranially. 
Insert the catheter perpendicular to the chest 
wall and, once in the subcutaneous space, 
apply 1–2 mL of vacuum with the syringe 
attached to the catheter extension tubing.
• Once the vacuum is lost, the tip of the 
needle can be directed so that it is away from 
the lung, and advanced along the inner 
pleura. The wings of the catheter can be 
pressed against the cranial rib and used to 
direct the needle in the pleural space.
Therapeutic Thoracocentesis
• Locate the point of insertion by counting to 
the 7th–9th intercostal space as described 
above. Position the needle at the widest point 
of the throax for air, and just dorsal to the 
costochondral arch for aspiration of fluid.
• If fluid is suspected, a few small fenest -
rations can be made in the catheter, starting 
1 cm proximal to the tip, to prevent clogging 
and increase yield:
 ◦Use a no. 11 blade and, while wearing 
sterile gloves, make small V-shaped holes by 
joining cuts at a 45° angle.Thoracocentesis and Fluid Analysis

Canine and Feline, Seventh Edition  1551
 ◦These holes should be no more than 20% 
of the circumference of the catheter.
 ◦Rotate the catheter 90° at each fenes -
tration to maintain the integrity of the 
catheter (i.e., fenestrations should not be 
opposite each other).
 ◦Do not scoop holes out; ensure that the 
edges are smooth to decrease the likelihood 
of the catheter getting caught on the skin 
and breaking.
• Lift the skin away from the body wall and 
make a stab skin incision that fully penetrates 
the dermis with the no. 11 blade.
• Attach the 3-mL syringe to the catheter–
needle assembly.
• The nondominant hand is rested on the 
animal and used to advance the catheter–
stylet assembly into the skin incision:
 ◦The stylet is advanced by the fingers of 
the nondominant hand, which is resting on 
the chest wall.
 ◦Once the needle has entered the 
subcutaneous space, the dominant hand 
applies 1–2 mL of vacuum using the syringe.
 ◦While maintaining the vacuum, advance 
the stylet slowly along the cranial aspect of 
the rib until the vacuum is lost (or fluid is 
observed), indicating that the pleural space 
has been entered.
• Once the stylet has entered the pleural 
space, advance the entire assembly approx -
imately ¼ inch:
 ◦Hold the stylet hub stationary and 
advance the catheter ≈1 cm over the stylet.
 ◦It is critical that the catheter is advanced 
and that the stylet is not pulled backward 
out of the pleural space.
 ◦Holding the stylet stationary, advance the 
catheter cranially into the thorax, parallel to 
the spine (for air) or cranioventrally (for fluid).
• Remove the stylet and have an assistant 
attach the extension set that has been 
connected to the three-way stopcock and 
syringe and begin aspiration.
Aliquots of effusion samples may be placed in 
EDTA tubes for cytologic analysis and tubes 
without additive or culturettes for bacterio -
logic culture. A slide should also be made for 
immediate cytologic evaluation.
• The patient’s respiration rate and effort 
should be monitored after thoracocentesis. 
Deterioration suggests that either the 
condition is worsening or that an iatrogenic 
pneumothorax has developed.
• Monitor the heart rate, pulses, and capillary 
refill time.
• Patients with recurrent pneumothorax after 
2–3 thoracocenteses will likely benefit from thoracostomy tube placement and continuous 
pleural suction.
No specific nursing care is necessary after the 
centesis.
N/A
Based on underlying disease.
The animal should remain quiet for a few 
hours after the thoracocentesis so that 
respiration rate and effort can be evaluated 
effectively. Further restrictions will be based 
on underlying disease.
The patient should recover as soon as the 
needle or catheter has been removed, and 
the sedation has worn off. Full recovery is 
based on the etiology of the underlying disease.
A normal patient should not have any air or 
fluid in its pleural space.
• If air is found, this indicates a 
• If fluid is found, indicating pleural effusion, 
it can be due to a number of causes, which 
can often be distinguished from one another 
by fluid cytology (see Fluid Analysis):
 ◦T ransudates, modified transudates, and 
pseudochylous effusion can be found in 
patients with heart failure.
 ◦The presence of intracellular bacteria or 
excessive numbers of neutrophils indicates a 
pyothorax.
 ◦Chyle may be present and is defined by 
fluid analysis and comparison with serum.
 ◦Neoplasia may be identified as well, 
although reactive mesothelial cells can have 
an appearance similar to neoplastic cells can 
caution is advised with diagnosis of 
If air is continuously being produced and 
removed with the catheter apparatus, or if the 
fluid is indicative of a pyothorax, a thorac -
ostomy tube should be placed to evacuate the 
pleural space more effectively.
None knownConditions That May Interfere 
Inadequate sedation will prevent safe and 
adequate thoracocentesis.
• The fluid can be contaminated, invalidating 
the results of microbial culture, if the fluid is 
not handled aseptically.
• A fresh slide preparation should always be 
made, especially if there is delay in evaluating 
the EDTA sample.
Species
None
Breed
None
Age
None
Gender
None
Pregnancy
None
• If the clinician is unsure whether the 
patient has pleural space disease, a diagnostic 
thoracocentesis should first be performed, 
especially if the patient is not stable enough 
for radiography.
• If the results of the diagnostic thoracocentesis 
are positive, a therapeutic thoracocentesis is 
recommended if the animal has an increased 
• The catheter technique is safer than using a 
needle because it decreases the likelihood of 
lung laceration.
• Samples should be evaluated to guide 
the clinician on how to treat the patient 
properly.
• Radiography or thoracic ultrasound can 
determine the need for thoracocentesis and 
post-procedure can assess the effectiveness of 
the thoracocentesis and identify underlying 
• Samples should be evaluated using approp -
riate fluid analysis, including cytologic 
evaluation. Based on these results, microbial 
culture of the fluid sample may be 
SYNONYMS
Chest tap(continued)  Thoracocentesis and Fluid Analysis

1552  Blackwell’s Five-Minute Veterinary Consult  
SEE ALSO
• Fluid Analysis (in Appendix X).
Washington State University, College of 
Veterinary Medicine, Small Animal 
Diagnostic & Therapeutic Techniques: 
Thoracocentesis: http://courses.vetmed.wsu.
edu/samdx/thoracocentesis.asp.
Hawkins E. Clinical manifestations of the 
pleural cavity and mediastinal diseases. In: Nelson RW, Couto CG, eds., Small Animal 
Internal Medicine. St. Louis, MO: CV 
Mosby, 2003, pp. 315–319.
Hawkins E. Diagnostic tests for the pleural 
cavity and mediastinum. In: Nelson RW, 
2003, pp. 320–326.
Mertens MM, Fossum TW, MacDonald KA. 
Pleural and extrapleural diseases. In: 
Veterinary Internal Medicine. Philadelphia, 
PA: W.B. Saunders, 2005, pp. 1272–1284.
Nelson OL. Pleural effusion. In: Ettinger SJ, 
Internal Medicine. Philadelphia, PA: W.B. 
Saunders, 2005, pp. 204–207.Rozanski E, Chan DL. Approach to the 
patient with respiratory distress. Vet Clin 
North Am Small Anim Pract 2005: 
315–316.
Sigrist NE. Thoracocentesis. In: Silverstein 
DC, Hopper K, eds., Small Animal Critical 
Elsevier, 2015, pp. 1029–1031.
Author  April Blong
Kielyn Scott.Thoracocentesis and Fluid Analysis  (continued)

Canine and Feline, Seventh Edition  1553
  BASICS
Diagnostic sample collection from the lower 
airway
T racheal wash involves insertion of a catheter 
into the airway of a dog or cat, injection 
of sterile saline for culture and cytologic 
evaluation, and subsequent aspiration of the 
fluid that has contacted the airway lining. 
The catheter can be inserted through an oral 
approach using a sterile endotracheal tube 
(endotracheal wash [ETW]) or through a 
transtracheal approach by passing sterile 
tubing through a catheter that is inserted 
between tracheal rings (transtracheal wash 
[TTW]). The catheter terminates at the carina 
for collection of a global airway sample.
Acute or chronic cough.
• Bleeding disorders.
• Anesthetic contraindications (for ETW).
• Markedly fractious animals (for the 
transtracheal approach).
• Any anesthetic complication.
• Subcutaneous emphysema.
• Pneumomediastinum.
• Cartilage damage.
• Cough may be transiently worsened after 
the procedure.
• Subcutaneous emphysema can develop.
  PROCEDURE
• Preoxygenate the patient for 5 minutes 
prior to the anesthesia.
• In cats, administer terbutaline (0.01 mg/kg 
SC) immediately prior to the procedure to 
counteract bronchoconstriction. Repeat if 
tachypnea or hemoglobin desaturation 
develops.
• Dogs with marked expiratory effort might 
also benefit from administration of 
terbutaline prior to the procedure, although bronchoconstriction is not a component of 
their disease.
• Local anesthesia with lidocaine is typically 
sufficient for a TTW in compliant patients. 
Mild sedation with acepromazine, 
butorphanol, or a benzodiazepine can be 
required. A TTW is a good choice for animals 
that are poor candidates for anesthesia.
• To perform an ETW, a mild anesthetic 
protocol that enables intubation and 5–10 
minutes of light anesthesia is necessary.
Sternal (some clinicians prefer positioning 
with the most affected side of the lungs 
ventrally for the transoral approach).
• Pulse oximetry can be used throughout an 
ETW along with standard anesthetic 
• If SC emphysema or bleeding develops 
during a TTW, the procedure should be 
aborted and stabilization and monitoring 
procedures instituted.
• ETW—sterile endotracheal tube, sterile 
gloves, sterile catheter or tubing, syringes, and 
sterile saline.
• TTW—local anesthesia (lidocaine), 
through-the-needle catheter (e.g., Intracath, 
BD, Franklin Lakes, NJ) or over-the-needle 
catheter and sterile tubing, syringes, and 
• If desired, a three-way stopcock and sterile 
container (e.g., mucous specimen trap) can be 
used in conjunction with house suction to 
facilitate retrieval of fluid.
TECHNIQUE
• A TTW is appropriate for use in dogs larger 
than 8–10 kg. This can be performed with an 
over-the-needle catheter (14–16 gauge) and 
3.5 French urinary catheter, or a through-the-
needle catheter (18 gauge, 8 or 12 inch):
 ◦The ventral portion of the neck is clipped 
and lightly scrubbed with antiseptic 
solution followed by alcohol wipes, and a 
more complete surgical preparation is 
performed after local anesthesia.
 ◦Lidocaine (0.25–0.5 mL, not to exceed 
2 mg/kg) is instilled into the subcutaneous 
tissue down to the level of the tracheal rings.
 ◦The catheter is inserted into the skin with 
the bevel of the stylet facing downward. 
The stylet is withdrawn and the urinary 
catheter is passed through the short catheter 
down the trachea.
 ◦An aliquot of nonbacteriostatic saline 
(4–10 mL) is injected into the catheter 
followed by 2–3 mL of air and then 
aspirated back into the syringe. Stimulation 
of a cough or chest compression after 
instillation can facilitate retrieval of a sample. ◦Fluid instillation and aspiration can be 
repeated 2–3 times until an adequate 
sample has been retrieved (0.5–1.0 mL is 
usually sufficient for culture and cytologic 
evaluation).
 ◦The long catheter is removed followed by 
the short catheter and a light wrap is 
applied to the neck.
 ◦If a through-the-needle catheter is used, 
the needle is used to puncture the trachea 
and then the urinary catheter is fed into the 
trachea. Once the catheter is entirely within 
the trachea, the needle is backed out of the 
skin, and the syringe with saline may be 
attached to the inserted catheter hub. The 
remainder of the procedure is as described 
above.
• An ETW is appropriate for use in large and 
small dogs, pediatric patients, and in cats. A 
sterile endotracheal tube and a sterile 
polypropylene catheter (3.5–8.0 French) or 
red rubber catheter are needed:
 ◦The animal is anesthetized with a 
short-acting anesthetic agent (e.g., propofol 
or alfaxolone, with premedication).
 ◦The sterile endotracheal tube is passed 
into the trachea, taking care to avoid 
touching the oral mucosa or larynx with the 
end of the tube in order to limit contamination 
with oropharyngeal bacteria.
 ◦An assistant holds the tube in place, and a 
sterile polypropylene catheter or red rubber 
tube is passed to the level of the carina 
(approximately the 4th intercostal space).
 ◦An aliquot of nonbacteriostatic saline  
(4–10 mL) is instilled into the airway 
followed by 2–3 mL of air, and gentle 
suction from the syringe is used to retrieve 
the fluid and cells from the lower airway. 
Alternately, house suction can be utilized 
with a mucous specimen trap, which can be 
connected to a tracheal suction catheter 
with a chimney valve.
Airway samples are submitted for cytologic 
evaluation and for bacterial culture. Aerobic, 
anaerobic, and Mycoplasma culture or PCR 
should be considered for individual cases, 
and the laboratory should be consulted for 
guidelines on sample submission. Aerobic 
culture can generally be submitted in a 
sterile red-top tube; however, some 
laboratories require Amies or charcoal 
medium for Mycoplasma  culture and an 
anaerobic culture tube to detect anaerobic 
bacteria.
• Monitor respiratory rate and effort.
• Watch for respiratory distress or appearance 
of SC emphysema.
• Monitor the TTW site for bleeding or 
swelling.Tracheal Wash

1554  Blackwell’s Five-Minute Veterinary Consult  
• Keep the animal quiet during recovery.
• If respiratory distress develops, placement 
in an oxygen-enriched environment can be 
helpful.
Any animal undergoing a tracheal wash 
should be fasted for 12–24 hours prior to the 
procedure, when possible.
None
• The use of leashes should be avoided for 
1–3 days after a transtracheal wash.
• Normal activity levels can usually be 
resumed after 1 day.
1–2 hours
• Normal animals should have ciliated 
respiratory epithelial cells present on cytologic 
evaluation and rare inflammatory cells or 
• Culture of airway fluid in normal dogs and 
cats can reveal light growth of various types of 
bacteria, including Pasteurella , Streptococcus , 
Staphylococcus , Acinetobacter , Moraxella , 
Enterobacter , Pseudomonas , Escherichia coli , 
and Klebsiella .
• Large numbers of neutrophils or 
bacteria are typically found in infectious 
processes.
• Abnormal lymphocytes can be suggestive of 
lymphoma.
• Airway parasites or protozoa may be 
evident on cytologic evaluation.
• Rarely, neoplastic cells may exfoliate into 
tracheal wash fluid.
• Infection can be documented by growth of 
a single species of pathogenic bacteria or by 
moderate growth of a mixed number of 
bacterial species.
• Detection of Mycoplasma  indicates infection.
• Corticosteroids will reduce the flux of 
inflammatory cells into the airways.
• Antibiotics will suppress bacterial growth 
on culture.
• Cough suppressants may make it difficult 
to obtain fluid from the airways.
• Severe tracheal sensitivity and tracheal or 
airway collapse can be worsened by trauma 
associated with tracheal wash.
• Airway collapse can result in poor return of 
fluid.
• In obese animals, a transtracheal wash can 
be difficult to perform because of an inability 
to palpate and stabilize the trachea.
• Room temperature saline may induce 
bronchoconstriction when infused in cats.
Upper airway contamination (indicated by 
the presence of squamous cells or Simonsiella 
bacteria on cytologic evaluation) influences 
culture results and increases the likelihood of 
growth of contaminating bacteria.
Species
• Dogs—TTW or ETW are appropriate, 
depending on size of the animal and ability to 
undergo anesthesia.
• Cats—ETW is appropriate.
Breed
• Caution should be employed when 
undertaking any respiratory procedure in 
brachycephalic animals.
• The size of animal will influence the 
decision to perform a TTW vs. ETW.
Age
Young dogs may be more likely to have 
Bordetella  and/or Mycoplasma  on culture than 
older dogs. Cartilage injury is more of a 
concern in  younger animals.
Gender
None
Pregnancy
None
T racheal wash procedures are relatively safe 
and easy to perform. Results of culture and 
cytologic evaluation provide valuable information on appropriate treatment of 
respiratory patients.
If results are nondiagnostic, consider 
bronchoscopy with bronchoalveolar lavage.
SYNONYMS
None
SEE ALSO
• Cough.
• Pneumonia, Bacteria.
• Pneumonia, Fungal.
• Pneumonia, Interstitial.
• ETW = endotracheal wash.
• TTW = transtracheal wash.
Dye JA, McKiernan BC, Rozanski EA, et al. 
Bronchopulmonary disease in the cat: 
Historical, physical, radiographic, 
clinicopathologic, and pulmonary 
functional evaluation of 24 affected and 15 
healthy cats. J Vet Intern Med 1996, 
10:385–400.
Peeters DE, McKiernan BC, Weisiger RM, 
et al. Quantitative bacterial cultures and 
cytological examination of bronchoalveolar 
lavage specimens in dogs. J Vet Intern Med 
2000, 14:534–541.
Randolph JF , Moise NS, Scarlett JM, et al. 
Prevalence of mycoplasmal and ureaplasmal 
recovery from tracheobronchial lavages and 
of mycoplasma recovery from pharyngeal 
swabs in dogs with and without pulmonary 
disease. Am J Vet Res 1993, 54:387–391.
swabs in cats with and without pulmonary 
disease. Am J Vet Res 1993, 54:897–900.
Consulting Editor  Benjamin M. BrainardTracheal Wash  (continued)

Canine and Feline, Seventh Edition  1555
Ultrasound‐Guided Mass or Organ Aspiration
  BASICS
Ultrasonographic
• Percutaneous ultrasound‐guided mass or 
organ aspiration is a technique that is 
commonly used to obtain material for 
cytologic examination as an aid in the 
diagnosis of a disease process:
◦ Ultrasonography is typically sensitive but 
not specific for disease processes, and 
additional information such as that 
obtained from cytologic examination of 
cellular material is often helpful in 
determining a definitive diagnosis.
◦ In addition, because needle placement 
can be directly visualized in real time, 
precise placement in an area of interest is 
possible.
• This procedure is commonly used to obtain 
cellular material from the liver, spleen, and 
kidneys with diffuse, infiltrative disease, as 
well as masses anywhere within the body.
• A prerequisite is that the area to be 
aspirated must be visible during ultrasonogra-
phy, and an unobstructed path for the needle 
trajectory must be identified:
◦ If there is gas or bone surrounding a 
lesion, then ultrasound guidance will likely 
not be possible.
Obtain a cellular or fluid sample for cytologic 
evaluation to further define or diagnose the 
etiology of an abnormality in an organ or 
mass.
• Superimposed structures in the path of the 
needle trajectory.
• Patient noncompliance.
• Inability to visualize the lesion definitively 
 POTENTIAL COMPLICATIONS
• Hemorrhage, which is typically self‐limiting 
unless a major vascular structure is damaged 
during the procedure or a severe coagulopathy 
• Sepsis or peritonitis if an abscess or infected 
lesion is sampled (rare).
• Possible seeding of neoplasia along the 
needle tract (rare).
Typically, the client should be apprised of the 
possible complications, but no additional 
education is necessary. If general anesthesia is 
required (because of patient noncompliance 
or a difficult‐to‐reach lesion), then typical preparation instructions should be given (e.g., 
withhold food).
  PROCEDURE
Pre‐Procedure Medication or 
• Withhold food and water as needed if 
anesthesia or sedation is necessary to 
accomplish the procedure.
• The skin in the area to be aspirated should 
be removed of hair (typically using clippers 
with a no. 40 clipper blade) and aseptically 
prepared.
• Alcohol may be used as an ultrasound‐cou-
pling agent to prevent any artifact that may 
occur in the cytologic preparation. (Ultrasound 
coupling gel can cause an artifact if it 
contaminates the slides during preparation.)
• To verify a safe needle trajectory, ultra-
sonography should be performed prior to the 
• Some patients will tolerate this procedure 
without anesthesia, sedation, or the use of 
local anesthetics. The need for sedation 
should be anticipated for anxious or painful 
patients and for intercostal approaches in the 
abdomen or thorax.
• If anesthesia or sedation is necessary, 
standard regimens may be used that are 
appropriate for the patient.
• It should be noted that protocols that cause 
panting or excessive splenic enlargement may 
make the procedure more difficult. For 
example, pure opioids may cause excessive 
panting and make it difficult to guide the 
needle into deep or small lesions.
Patients should be positioned to enable an 
unobstructed approach and placement of 
both the needle and the transducer. Typically, 
patients will be positioned in lateral or dorsal 
recumbency, and they should be manually 
restrained if anesthesia is not used.
None, except as indicated during sedation or 
anesthesia.Equipment or Supplies
Typically, a 22‐gauge needle of appropriate 
length attached to a syringe (6 or 12 mL) is 
used. Small needles (23, 25, or 27 gauge) may 
be used particularly if hemorrhage is felt to be 
a significant risk. However, nondiagnostic 
samples may be obtained with smaller gauge 
needles.
TECHNIQUE
• There are three methods used to perform a 
percutaneous ultrasound‐guided mass or 
organ aspiration. In any case, the shortest 
trajectory between the skin surface and the 
lesion should be chosen. Only one body cavity 
should be penetrated at a time. In addition, 
choice of ultrasound transducer type can affect 
the ease of performing the procedure. Convex 
or sector‐type transducers usually have a 
smaller footprint and thus are easier to 
manipulate when performing this procedure. 
A linear transducer may be difficult to use 
because it has a larger footprint:
◦ Indirect technique: This technique 
involves using ultrasonography to identify 
the lesion to be sampled, and then the 
transducer is removed and the needle is 
passed blindly into the structure to be 
sampled. This technique may be used if the 
lesion is extremely large, and thus confirma -
tion of needle placement is not necessary.
◦ Freehand technique: This is the most 
commonly employed technique. The needle 
is held in one hand and the transducer is 
held in the other. The area of interest 
should be visualized, and the probe is 
manipulated such that the lesion is clearly 
visible. The needle should puncture the 
skin a few millimeters away from the 
transducer in order to facilitate needle 
visualization, as well as to protect against 
puncturing the transducer. The goal is to 
pass the needle within the plane of the 
ultrasound beam so that the needle is 
visible. Do not pass the needle in a plane 
perpendicular to the ultrasound plane, 
because the length will not be visible. The 
more acute the needle angle is to the 
ultrasound beam, the more difficult it is to 
visualize the needle. Therefore, the needle 
should form at least a 45° angle with the 
transducer to facilitate its visualization. The 
needle is passed through the skin and then 
into the lesion of interest.
◦ Guided technique: The needle is held in 
place by using an attachable guide, which is 
coupled to the transducer (see Figure 1). 
The ultrasound machine will have software 
that will show the projected trajectory of 
the needle. The area of interest is visualized, 
and the transducer is manipulated such that 
the projected path of the needle is 
superimposed over the area to be sampled. 
The needle is then passed through the

1556  Blackwell’s Five-Minute Veterinary Consult  
needle guide attached to the transducer and 
into the patient.
• If using either the freehand or the guided 
technique, improved needle visualization may 
be obtained either by moving the needle 
slightly, by moving the needle in and out of 
the tissue, or by minimally adjusting the 
transducer to bring the needle more into the 
plane of the ultrasound beam.
• Using any of the aforementioned methods, 
the sample may be obtained either through 
direct aspiration with active suction applied 
to the syringe while the needle tip is in the 
lesion or through a nonaspiration technique 
whereby the needle is moved up and down in 
the area of interest several times before the 
needle is withdrawn from the patient.
• Any organ or mass can be aspirated by using 
any of these techniques. If a diffuse disease is 
suspected in the liver, it is usually best to 
aspirate the left side of the liver to help prevent 
possible laceration of the gallbladder. In 
addition, the spleen is typically sampled by 
using a nonaspiration technique to help 
prevent hemodilution of the sample. It may be 
advantageous to obtain at least 1 sample by 
using an active aspiration technique and 1 
sample by using a nonaspiration technique (in organs other than the spleen) to maximize the 
chance of obtaining a diagnostic sample. Active 
aspiration may disrupt fragile cells such as seen 
in lymphoma:
◦ To practice aspiration or biopsy techniques, 
a biopsy phantom can be created. A biopsy 
phantom can improve the hand‐to‐eye 
coordination necessary to perform these 
techniques successfully, particularly the 
freehand technique, which requires more 
practice for proficiency (see Figure 2).
◦ The simplest biopsy phantom uses a heavy 
plastic bag. (An empty IV saline bag works 
well.) Culinary gelatin is mixed at double the 
recommend concentration and poured into 
the bag. After 15–30 minutes of refrigeration, 
as the gelatin begins to set, targets are inserted 
into the middle of the gelatin. (Grapes, 
cherries, and chickpeas work well.) Care 
should be taken to not create any air bubbles. 
The gelatin is allowed to set completely, and 
then the bag is sealed. The outer surface can 
then be imaged and a needle passed easily 
through the bag to the target.
The cytologic sample should be placed onto a 
microscope slide. Disconnecting the needle 
from the syringe and filling it with air usually facilitates this (see Fine‐Needle Aspiration). 
The needle is then reattached, and a rapid 
expulsion of the air in the syringe will force 
the cellular sample in the hub of the needle 
onto a microscope slide.
Post‐Procedure Patient Monitoring
The patient should be monitored immedi-
ately after the procedure in order to verify 
that significant hemorrhage is not occurring. 
This may be more common in patients with 
ascites. The duration of monitoring is variable 
depending on the individual patient and its 
specific problems.
None
None
None
None typically needed.
Immediately
Figure 1 .
A transducer with a needle guide attachment in place. The guide will maintain the needle in the 
plane of the ultrasound beam and, combined with the software program on the machine, will 
enable specific placement of a needle or biopsy instrument in the area of interest. Source: Lawrence 
P . TilleyUltrasound‐Guided Mass or Organ Aspiration  (continued)

Canine and Feline, Seventh Edition  1557
N/A
N/A
N/A
The use of opioids and other drugs that cause 
splenomegaly should be avoided because they 
may compromise the procedure.
• A lesion that is surrounded by air or bone 
and cannot be visualized by using ultrasound.
• Patient noncompliance.Procedure Techniques or Handling That 
• Excessive hemodilution or rough handling 
of the cellular material may result in a 
nondiagnostic sample.
• If appropriate orientation of the needle 
with the ultrasound plane is not maintained, 
the needle might not be visualized in the 
ultrasound image and inappropriate sampling 
may occur.
• Fluid within a cavitated mass or cystic 
lesion may not contain diagnostic cells.
Species
None
Breed
None
Age
None
Gender
NonePregnancy
None
organ aspiration should be used to help 
further define the etiology of an infiltrative 
process or mass.
• This procedure is quick and generally safe 
when performed by an experienced 
practitioner.
• Both active aspiration and nonaspiration 
techniques may be necessary to obtain a 
diagnostic sample.
If the cytologic sample is nondiagnostic, then 
a needle biopsy sample may be obtained by 
using the same principles as for obtaining a 
cytologic sample. Typically, sedation or general 
anesthesia is required for this procedure.
Figure 2.
Image obtained during aspiration of focal splenic thickening. The needle is especially conspicuous 
because the lesion is close to the skin surface, a high‐frequency tranducer was used, the needle angle 
is acute, and the needle is wholly within the plane of the ultrasound beam. Real‐time scanning 
during the procedure can compensate for less optimal imaging conditions, usually allowing ade -
quate needle visualization. Source: Lawrence P . Tilley(continued)  Ultrasound‐Guided Mass or Organ Aspiration

1558  Blackwell’s Five-Minute Veterinary Consult  
SYNONYMS
None
SEE ALSO
Fine‐Needle Aspiration (in Appendix X).
None
Nyland TG, Mattoon JS, Herrgesell EJ, 
Wisner ER. Ultrasound‐guided biopsy. In: 
Nyland TG, Mattoon JS, eds., Small 
Animal Diagnostic Ultrasound, 2nd ed. Philadelphia, PA: W.B. Saunders, 2002, 
pp. 30–48.
Nyland TG, Wallack ST, Wisner ER. 
Needle‐tract implantation following us‐
guided fine‐needle aspiration biopsy of 
transitional cell carcinoma of the bladder, 
urethra, and prostate. Vet Radiol 
Ultrasound 2002, 43:50–53.
Pennick DG, Finn‐Bodner ST. Updates in 
interventional ultrasonography. Vet Clin 
North Am Small Anim Pract 1998, 
28:1017–1040.Samii VF , Nyland TG, Werner LL, Baker 
TW. Ultrasound‐guided fine‐needle 
aspiration biopsy of bone lesions: a 
preliminary report. Vet Radiol Ultrasound 
1999, 40:82–86.
Author  Mason Holland
Consulting Editor  Benjamin M Brainard
acknowledge the prior contribution of Ann 
Bahr.Ultrasound‐Guided Mass or Organ Aspiration  (continued)

Canine and Feline, Seventh Edition  1559
Urethral Catheterization
  BASICS
for evaluation of ill dogs and cats and for 
routine health screening of all patients:
◦ Sterile sample collection is required for 
culture and sensitivity testing of urine when 
infectious cystitis is suspected.
◦ In those cases where cystocentesis is 
contraindicated or unsuccessful at obtaining 
urine, urethral catheterization enables 
sterile urine samples to be collected with 
minimal risk to patients.
• Patients in need of exact calculation of 
urine output (e.g., those with anuric or 
oliguric renal failure), patients with functional 
or mechanical urethral obstruction, and many 
recumbent animals often require intermittent 
or indwelling urinary catheterization as part 
of their management plan.
• Urethral catheterization is required in order to 
perform other diagnostic procedures such as 
prostatic wash, cystourethrography, and voiding 
or catheter-assisted hydropropulsion of uroliths.
• Sterile urine collection when cystocentesis is 
• Temporary relief of urethral obstructions.
• Collection of urine for fluid-output 
determination or metabolic testing (e.g., 24 
hour collection of urine for calculation of 
electrolyte excretion).
• Management of recumbent patients.
Severe vaginitis or balanoposthitis.
• Iatrogenic bacterial or fungal cystitis.
• Urethral trauma (perforations or tears, 
stricture formation).
None
  PROCEDURE
None
• Male dogs typically require minimal to no 
sedation.• Female dogs and both male and female cats 
usually require heavy sedation or anesthesia.
• Hydropulsion of urethral obstructive 
materials is frequently most successful in a 
very relaxed animal; in difficult cases, the 
deepening of sedation or even general 
anesthesia may allow catheterization.
• Male dogs—lateral recumbency.
• Male cats—dorsal recumbency.
• Female dogs and cats—sternal recumbency 
with their legs tucked underneath or extended 
over the edge of a table.
None
• Hair clippers.
• Diluted povidone-iodine (Betadine) or 
chlorhexidine solution: 1 part povidone-
iodine or chlorhexidine solution to ≈200 
parts sterile saline.
• A sterile 12-mL syringe.
• Sterile lubricating jelly.
• T wo sets of 4 × 4-inch gauze sponges 
soaked in sterile saline and chlorhexidine or 
povidone-iodine solution.
• Povidone-iodine scrub should not be used 
on the genital mucous membranes.
• A sterile urinary catheter (Foley catheter, 
red rubber catheter (polyurethane or silicone), 
tomcat (polypropylene), or slippery sam 
(polytetrafluroethylene) catheter of 
appropriate size). If using a Foley catheter, 
inflate the balloon prior to catheterization to 
assess for leaks:
◦ Polyurethane, silicone, and 
polytetrafluroethylene catheters are softer 
and likely to be better tolerated than the 
stiffer polypropylene catheters for long-
term catheterization.
• In female dogs, if the visualization method 
is being used:
◦ A disinfected vaginal speculum.
◦ A light source.
• If the urinary catheter will be indwelling:
◦ A closed collection system.
◦ Materials for anchoring the catheter to the 
patient (e.g., bandage tape, suture material).
TECHNIQUE
Male Dogs
• For indwelling catheters, clip the hair on 
the distal one-third of the prepuce. Clipping 
the hair on the ventral abdomen around the 
preputial opening to a distance of 2–5 cm 
may also reduce the risk of iatrogenic 
• Flush the prepuce 3–5 times with 2–12 mL 
of dilute povidone-iodine solution (the 
volume depends on the size of dog) by using 
the sterile syringe.
• An assistant should exteriorize the penis. 
This is best done with the assistant standing at the dog’s back (while the animal is in lateral 
recumbency), and the individual placing the 
catheter standing at the dog’s ventrum.
• Clean the extruded penis with sterile 4 × 
4-inch gauze sponges, alternating between 
chlorhexidine or povidone-iodine solution 
and sterile saline. A minimum of three scrubs 
should be performed with each solution.
• Flush the penis with 2–5 mL of dilute 
• After donning sterile gloves, coat the distal 
catheter with lubricating jelly. Using sterile 
technique, insert the urinary catheter. The 
catheter should be gently advanced until 
urine is seen in the distal end of the catheter. 
Some resistance may be encountered when 
the catheter passes around the ischial arch, 
but gentle pressure is usually sufficient to 
overcome this. Care should be taken not to 
advance the catheter too far into the bladder 
because in rare cases the catheter may knot 
inside the bladder, making removal difficult.
• For patients with urethral obstruction, 
pulsative flushing of small volumes (1–2 mL) 
of sterile saline through the catheter may 
distend the urethra and retropulse the 
obstructive material into the bladder, 
facilitating catheterization.
• Red rubber catheters can be used for 
indwelling or intermittent catheters in male 
dogs, but Foley catheters are preferred for 
indwelling catheters:
◦ If a Foley catheter is used, inflate the 
bulb with sterile saline after the catheter has 
been advanced to the bladder.
• Immediately connect a sterile, closed 
collection system to the indwelling catheter.
• Anchor the indwelling catheter as needed to 
prevent displacement:
◦ Most common method is to place bandage 
tape around the catheter ≈2–4 cm cranial to 
the preputial opening, with tabs on either 
side. Sutures are then passed through the 
tabs and attached to the body wall.
Female Dogs
• Clip the hair around the vulva, including 
the perineal area, to a distance of 2–5 cm 
from the vulva.
• Scrub the vulva and perivulvar area with 
sterile 4 × 4-inch gauze sponges, alternating 
between chlorhexidine or povidone-iodine 
solution and sterile saline. A minimum of 
three scrubs should be performed with each 
solution.
• Flush the vaginal vault 3–5 times with 
2–12 mL of dilute povidone-iodine or 
chlorhexidine solution (the volume depends 
on the size of dog) by using the sterile syringe.
• Sterile lidocaine jelly can be flushed into 
the vulva using a clean, lubricated syringe 
with the needle removed.
• Visualization technique:
◦ After donning sterile gloves, insert the 
vaginal speculum with its handles pointing

1560  Blackwell’s Five-Minute Veterinary Consult  
dorsally. The speculum is then advanced 
dorsally and cranially over the pelvic brim 
and spread until the urethral papilla and 
urethral orifice are seen (see Figure 1).
◦ Visualization is improved by use of a 
speculum with an attached light source or a 
headlamp or by an assistant who stands 
behind the individual placing the catheter 
and illuminates the vaginal vault with the 
light source.
◦ The urethral papilla is on the ventral 
midline of the vaginal floor, distal to the 
cervix (Figure 1).
◦ Coat the catheter with the lubricating 
jelly and then, using sterile technique, place 
the urinary catheter. Foley catheters are 
preferred for indwelling catheters. Red 
rubber catheters, though they can be used 
in female dogs, are easier to dislodge than 
in male dogs because a significantly shorter 
length of the catheter is inserted. Inflate the 
balloon if a Foley catheter is used and 
gently retract the catheter until the balloon 
is seated in the bladder trigone.
• Digital palpation technique:
◦ After donning sterile gloves, lubricate the 
index finger of the nondominant hand and 
insert into the vaginal vault, advancing 
cranially and dorsally over the pelvic brim 
until the urethral papilla is palpated at the 
fingertip.◦ Coat the distal catheter with the 
lubricating jelly and then, using sterile 
technique, place the urinary catheter. The 
catheter should be advanced along the 
ventral aspect of the inserted index finger 
and then guided into the urethral orifice by 
• A blind placement technique as described 
below for female cats may be necessary for 
very small dogs.
• Use of a stylet may increase rigidity of the 
catheter facilitating placement into the 
urethral orifice. If a stylet is used it should be 
kept fully within the catheter to prevent 
trauma to the urethra.
pulsatile flushing of small volumes (1–2 mL) 
• Anchor the urinary catheter to prevent 
displacement. Bandage tape can be used as 
described previously for male dogs, suturing 
the catheter to the body wall ventral to the 
vulva. Alternatively, if a Foley catheter was 
used, the balloon will anchor the catheter in 
the bladder, and the catheter/collection 
system may be stabilized using tape to the 
dog’s tail, or to an area just above the hock, to avoid fecal contamination and inadvertent 
removal.
Male Cats
• A coccygeal epidural block may provide 
analgesia to the perineum, penis and urethra, 
and can facilitate catheterization in cats with 
urethral obstruction:
◦ With the patient in sternal recumbency, 
palpate the space on dorsal midline between 
the sacrum and first coccygeal vertebrae. 
Moving the tail up and down may help to 
identify this landmark as the sacrum is 
immobile but the coccygeal vertebrae will 
be mobile when the tail is manipulated.
◦ Clip the fur over this site and prepare it 
◦ Wearing sterile gloves, palpate and 
reconfirm the location of the space between 
the sacrum and the first coccygeal vertebrae. 
Slowly insert a 25-gauge, 5/8-inch needle 
on midline at a 30–45° angle into the 
epidural space.
◦ Attach a 1 mL slip-tip syringe and gently 
aspirate; if blood is aspirated the needle 
should be removed and repositioned.
◦ If no blood is aspirated, slowly infuse 
0.1 mL/kg of 2% lidocaine into the 
epidural space. If the needle was correctly 
positioned, little resistance should be noted.
◦ Following injection, withdraw the needle 
and assess for relaxation of the rectum and tail.
Figure 1 .
The vaginal vault of a female dog, as viewed during 
urethral catheterization. The urethral papilla with 
central orifice is located on the ventral midline. 
Source: Lawrence P . TilleyUrethral Catheterization  (continued)

Canine and Feline, Seventh Edition  1561
◦ A coccygeal epidural block is contra -
indicated in patients with thrombo -
cytopenia, coagulopathy, hypotension, skin 
disease at the injection site, or when 
anatomic abnormalities are present.
• Clip the hair around the prepuce, including 
the perineal area, to a distance of 1–2 cm 
from the preputial opening.
• Tomcat catheters (open-ended) can be 
used for intermittent catheterization; 
open-ended catheters or catheters with a 
removable stylet are the preferred catheter 
for relieving urethral obstruction in male 
cats. Red rubber catheters or Foley catheters 
(close-ended) should be used for indwelling 
urinary catheters.
• An assistant should exteriorize the penis, 
which is best done with the assistant standing 
at the cat’s head or side (while the animal is in 
dorsal recumbency).
• Proper exteriorizing of the penis is critical 
for successful passage of urinary catheters in 
male cats. Gentle pressure at the base of the 
prepuce will cause the penis to extrude.
• The penis should be completely exteriorized 
and pointed caudally, parallel to the spine. 
Attempting to pass the urinary catheter when 
the penis is not at the correct angle increases 
the risk of significant urethral trauma and will 
prevent the catheter from passing:
◦ Clean the extruded penis with sterile 4 × 
and sterile saline. A minimum of three 
scrubs should be performed with each 
solution.
◦ After donning sterile gloves, coat the 
distal catheter with lubricating jelly.
◦ Using sterile technique, place the urinary 
catheter. The catheter should be gently 
advanced until urine is seen in the distal 
end of the catheter, taking care not to 
advance the catheter too far into the 
bladder.
◦ It may be necessary to grasp the prepuce 
and apply caudal traction while advancing 
the catheter to straighten the urethra to 
allow passage.
◦ For patients with urethral obstruction, 
pulsatile flushing of small volumes 
(1–2 mL) of sterile saline through the 
catheter may distend the urethra and 
retropulse the obstructive material into the 
bladder, facilitating catheterization.
◦ If the bladder is already distended due to 
obstruction, it may be necessary to perform 
cystocentesis to relieve back pressure and 
allow infusion of saline and placement of the 
catheter.
collection system for indwelling catheters.
• Anchor the catheter as needed to prevent 
displacement. In addition to this anchor, red rubber catheters are frequently secured with tape 
to the cat’s tail ≈4–6 cm caudal to the anus.
Female Cats
solution and sterile saline. A minimum of three 
scrubs should be performed with each solution.
0.5–2.0 mL of dilute povidone-iodine 
solution (the volume depends on the size of 
cat) by using the sterile syringe.
• Urethral catheterization of female cats is 
performed blindly.
catheter with the lubricating jelly. With the 
cat in sternal recumbency and its legs 
extended (which is most easily done with the 
legs allowed to dangle from the edge of a 
table), the catheter is inserted into the vulva 
and advanced slowly. The catheter usually 
enters the bladder without difficulty.
• Tomcat catheters can be used for 
intermittent catheterization. Red rubber 
catheters should be used for indwelling 
urinary catheters due to the softer material.
displacement. The most common method is to 
place bandage tape around the catheter 
≈2–4 cm cranial to the vaginal opening, with 
tabs on either side. Sutures are then passed 
through the tabs and attached to the body wall.
analyzed immediately if possible; refrigeration 
for later analysis can alter some dipstick and 
sediment findings.
be refrigerated, ideally in a culture transport 
vial, until plated onto appropriate media.
None
Indwelling urinary catheters should be kept 
clean. The external portion of the catheter 
should be cleaned every 24 hours (or more 
frequently, as needed) with 4 × 4-inch gauze 
soaked in chlorhexidine or povidone-iodine 
solution and sterile saline.
NoneMedication Requirements
• Prophylactic antibiotics for the prevention 
of urinary tract infection should not be 
administered to patients with indwelling 
urinary catheters. This practice increases the 
risk of hospital-acquired resistant infections 
and has not been shown to prevent infection.
• Animals with indwelling urinary catheters 
should have urine cultured at the time of 
catheter removal. Bacterial colonization of 
indwelling urinary catheters is possible, and 
therefore urine culture results drawn from 
indwelling catheters should be interpreted 
with caution.
Elizabethan collars should be placed on 
nonrecumbent patients with indwelling 
Immediate
N/A
N/A
Urethral obstruction that cannot be relieved 
by urethral catheterization requires surgical 
intervention, although deeper anesthesia 
combined with cystocentesis may allow 
relaxation and catheterization.
Drugs that increase urethral tone (e.g., phenyl -
propanolamine, di-ethylstilbestrol) may 
theoretically make catheterization more difficult. 
However, this is likely not clinically significant.
Conditions That May interfere 
• Urethral obstruction by masses, 
inflammation, urethrospasm, urethroliths, 
matrix and mucous plugs, stricture, or 
extramural masses.
• Pelvic trauma.
Loss of sterility or contamination of the 
catheter during placement predisposes 
patients to development of iatrogenic urinary 
and interpreting the Procedure
Species
See the Technique section.(continued)  Urethral Catheterization

1562  Blackwell’s Five-Minute Veterinary Consult  
Breed
None
Age
Placement of urinary catheters in neonatal or 
pediatric patients can be very difficult. Red 
rubber catheters are ideal because they are less 
likely to cause iatrogenic trauma during 
placement.
Gender
See the Technique section.
Pregnancy
None
• Urethral catheterization is underused as a 
method for obtaining sterile urine samples, 
particularly in those patients where repeated 
cystocentesis attempts are unsuccessful at 
obtaining a urine sample.
• If urine is being collected for culture, the 
first 3–10 mL of urine drawn from the 
catheter should be discarded, after which the 
sample for culture is collected. This is recommended because the distal urethra and 
vaginal vault are not sterile environments and 
often cause some contamination of the 
catheter tip during placement and because 
indwelling catheters may have bacterial 
colonization of the catheter lumen.
• Urine culture.
• Contrast cystourethrogram.
SYNONYMS
• Indwelling urinary catheter.
• Urinary catheterization.
SEE ALSO
• Acute Kidney Injury.• Urinary T ract Obstruction.
O’Hearn AK, Wright BD. Coccygeal epidural 
with local anesthetic for catheterization and 
pain management in the treatment of feline 
urethral obstruction. J Vet Emerg Crit Care 
2011, 21(1):50–52.
Smarick SD, Haskins SC, Aldrich J, et al. 
Incidence of catheter-associated urinary 
tract infection among dogs in a small 
animal intensive care unit. J Am Vet Med 
Assoc 2004, 224:1936–1940.
acknowledge the prior contribution of Barak 
M. Pressler.Urethral Catheterization  (continued)

Canine and Feline, Seventh Edition  1563
  BASICS
Urine
A urinalysis (UA) is a basic diagnostic 
screening test that is easy to perform, 
relatively inexpensive, and can be useful in 
evaluating renal/urologic and nonrenal 
conditions. A complete UA includes the 
following components:
• Physical characteristics: volume, odor, color, 
transparency, and solute concentration (e.g., 
urine specific gravity [USG]).
• Chemical characteristics: presence of 
bilirubin, blood, glucose, ketones, pH, and 
protein. Some tests available on dipsticks 
(e.g., urobilinogen, nitrite, leukocytes, esterase, 
USG) may be unreliable, of no value, or not 
validated for veterinary species.
• Microscopic evaluation of urine sediment: 
cells, crystals, casts, organisms, and other 
(e.g., sperm, lipid, mucus).
• UA, part of the minimum data base, is used 
in conjunction with complete blood count 
(CBC) and clinical chemistry to establish 
baseline for initial workup.
• Assessment of kidney function: 
concentrating ability of solutes (e.g., USG); 
filtering and resorptive handling of electrolytes, 
protein, glucose; and response to acid–base 
• Detection of hemorrhage, inflammation, 
infection, or neoplasia in the urinary or 
genital tract.
• Evaluation of systemic disorders or 
diseases.
None
Hemorrhage or inadvertent enterocentesis can 
occur with cystocentesis.
If an owner collects urine, it should be put 
into a clean container free of any type of 
contaminant (e.g., detergents or disinfectants).
• Reproductive.  SAMPLE
5–10 mL of urine collected by free catch of a 
voided sample, manual expression of the 
urinary bladder, catheterization, or 
• Collect urine into a clean, dry container 
with a tight-fitting lid and free of potential 
contaminants (e.g., detergents, disinfectants). It 
should be labeled with appropriate information 
(e.g., patient and owner identification; date, 
time, and method of collection).
• Results are most accurate if urine is 
analyzed within 30–60 minutes after 
• The sample should be refrigerated if a delay 
in analysis is unavoidable.
• Refrigerated samples should be warmed to 
room temperature before analysis.
• Refrigeration can slow sample deterioration. 
The container should protect the sample from 
light and have a tight-fitting lid.
• Refrigeration may alter some results (e.g., 
increased crystal formation).
• Avoid freezing the urine because this will 
affect certain tests (e.g., urine sediment 
examination).
• Preservatives generally adversely affect 
chemical assays. No single preservative suits 
all testing requirements.
Components analyzed in urine sediment (i.e., 
cells, casts, crystals, bacteria) deteriorate 
rapidly (within 2–4 hours). Over time, CO2 
is lost from the stored sample, increasing pH, 
and bilirubin may degrade with exposure to 
light or spontaneously oxidize (stable for up 
to 12 hours refrigerated). Most other 
chemical tests are stable for 12 hours in a 
refrigerated sample.
PROTOCOL
• Mix the sample and transfer it to a 
• Evaluate the physical features of the urine 
(i.e., volume, odor, color, turbidity).
• Determine the USG by using a refracto- 
meter.
• Measure urine analytes by using a reagent 
strip:
 ◦Immerse a reagent strip into well-mixed, 
room-temperature urine and turn the strip 
on its side, tapping away excess urine.
 ◦Examine the color change of each analyte 
at the time indicated by the manufacturer and compare the color change to the 
reference chart.
 ◦Confirmatory tests are affected less by 
urine color and may be warranted to 
confirm specific dipstick analyte results. 
Such tests include the Ictotest® (Siemens, 
Tarrytown, NY) for bilirubin, the 
K-CHECK® (Biorex Labs, Cleveland, OH) 
for ketones, and sulfosalicylic acid test 
(SSA) for protein.
 ◦Automated dipstick readers are available.
• Centrifuge the sample for 5–10 minutes at 
low RPM in a conical tube:
 ◦Ideally, the same volume of urine should be 
centrifuged each time, and reference values are 
based on 5 mL of urine. Analysis of smaller 
urine volume should be noted on the final 
report because that can result in less sediment.
 ◦The recommended RPM is quite variable 
(500–3,000 RPM) because it is actually 
gravitation force ( g-force) that is important. 
A g-force of 450× g is recommended. See 
Internet Resources for a conversion 
program between RPM and g-force.
 ◦Excessively high-speed centrifugation can 
distort cells or fragment fragile elements 
such as casts.
• Use urine supernatant to measure protein 
by the SSA method. If urine is bloody or 
extremely cloudy, double check the USG by 
using supernatant.
• Decant the supernatant, leaving ≈0.5 mL of 
• Resuspend the sediment and transfer a drop 
to a microscope slide.
• Coverslip and examine the sample micro- 
scopically at 10× and 40× (see Urine Sediment).
• Fresh urine should be relatively clear, 
yellow, and have a slight ammonia odor. 
Intact male cat urine may have a strong odor.
• The USG should be evaluated based on 
the hydration status. In general, the urine 
concentration from a random urine sample is 
considered adequate if the USG is >1.035 and 
>1.040 in dogs and cats, respectively, although 
USG can vary significantly depending on the 
state of hydration in normal animals.
• Normal urine should have a pH between 
6.0 and 7.5, and should be negative for 
protein, ketones, blood, bilirubin, and 
glucose. Some dogs with highly concentrated 
urine may show a trace to 1+ reaction for 
bilirubin and/or protein.Urinalysis Overview

• Urine sediment should contain few cells 
and crystals and no casts. Lipid is seen 
occasionally in cat urine.
• USG should be greater than 1.030 in 
patients with azotemia. Consistently 
isosthenuric urine in non-azotemic animals 
may reflect renal or nonrenal disease. 
Hyposthenuria (USG <1.008) indicates an 
inability to concentrate secondary to a 
nonrenal disease (e.g., diabetes insipidus) 
because a functional kidney must be present 
to dilute the urine below isosthenuria.
• Urine pH should mirror the blood pH; in 
academic patients with alkaline urine, 
consideration should be given to urinary 
bicarbonate loss (renal tubular acidosis) or 
urinary tract infection with urease-producing 
bacteria. Many drugs and prescription diets 
can either raise or lower the urinary pH, and 
a complete history should be taken to put 
urinalysis results into context.
• Urine glucose may be elevated due to 
persistent or paroxysmal hyperglycemia (see 
Hyperglycemia), and should be interpreted in 
concert with the serum glucose. Some renal 
tubular defects will also result in persistent 
glucosuria without hyperglycemia (e.g., 
Fanconi’s syndrome).
• Urine ketones will be elevated in states of 
ketonemia, (e.g., diabetic ketoacidosis, 
starvation). Because the strip only detects 
acetoacetate and acetone, animals with 
beta-hydroxybutyrate ketonemia may 
generate a negative test.
• Urine protein in urine with inactive 
sediment may be indicative of glomerular or 
renal tubular disease or hereditary glomerulo -
pathy. Proteinuria is an appropriate condition 
accompanying urinary tract inflammation or 
infection. Proteinuria in inactive urine 
samples should be further investigated 
through the measurement of a urine 
protein:creatinine ratio.
• Urine bilirubin is found in concentrated 
canine urine samples in small amounts, but 
should not be found in dilute canine urine or 
feline urine. Its presence generally indicates 
elevated serum bilirubin concentration and 
may be due to any systemic causes of 
hyperbilirubinemia (hepatic, prehepatic, or 
posthepatic).
• Urine heme protein is positive in the 
presence of hemoglobin, myoglobin, or red blood cells, and as such may indicate systemic 
disease or hemolysis, or urinary tract 
hemorrhage, which can result from thrombo -
cytopenia, neoplasia, or cystitis, among other 
conditions. Pigmenturia may be differentiated 
from hematuria through centrifugation of a 
urine sample, wherein the red blood cells will 
be pelleted, while pigment will remain in the 
supernatant.
Variable depending on assay; diabetic 
ketoacidosis requires emergency care, and 
animals with significant proteinuria and 
azotemia may be at risk for complications 
associated with protein-losing nephropathies. 
Pigmenturia/hematuria may be indicative of 
life-threatening coagulopathy, hemolysis, or 
other diseases associated with anemia or 
muscle damage (e.g., heat stroke, crotalid 
envenomation).
Drugs That May Alter Results or Interpretation
Drugs That Interfere With T est 
Certain drugs or metabolites excreted into the 
urine may impart characteristic odors. Hydro -
xethyl starch and radiographic contrast agents 
can alter USG measurements; radiographic 
contrast agents can also interfere with some 
biochemical analytes or cause crystal 
formation. Cephalexin, tetracycline, and 
vitamin C therapy may be associated with 
false-positive readings for urine glucose.
• Method of collection can influence 
findings:
 ◦Voided and free catch samples or samples 
obtained by manual expression contain 
components from lower urogenital tract 
and may have increased bacteria, epithelial 
cells, or leukocytes.
 ◦Cystocentesis samples may be 
contaminated with iatrogenic hemorrhage.
 ◦Samples from catheterization can contain 
increased bacteria, and/or epithelial cells, 
reflect iatrogenic hemorrhage, or be 
contaminated with lubricant.
 ◦Samples obtained from a surface (e.g., 
floor, examination table, cage) may contain 
bacteria, debris, or other environmental 
contaminants.• Reagent strips should be stored at room 
temperature in the original container; 
protected from excessive light, moisture, and 
heat; not used past the expiration date; and 
discarded if any of the pads on the strips are 
discolored.
• The ketone reagent pad is only sensitive for 
detecting acetoacetate and acetone, so if a 
patient has beta-hydroxybutyrate ketonuria, 
this will not be detected, but can be measured 
in the blood using hand-held devices (See 
Diabetes Mellitus with Ketoacidosis).
• Pigmenturia of any cause may interfere 
with reading the colorimetric results.
Yes.
Urine protein:creatinine (UPC) ratio is 
indicated if proteinuria is observed with an 
inactive sediment (i.e., no hematuria, pyuria, 
or bacteriuria).
• UA = urinalysis.
• UPC = urine protein:creatinine ratio.
  INTERNET RESOURCES
• http://eclinpath.com/urinalysis/
• Kobuta, Laboratory Centrifuge: g-force 
calculation: http://www.centrifuge.jp/
calculation/
Callens AJ, Bartges JW. Urinalysis. Vet Clin 
Small Anim 2015, 45:621–637.
Chew DJ, DiBartola SP . Urinalysis 
interpretation. In: Interpretation of Canine 
and Feline Urinalysis. Wilmington, DE: 
Ralston Purina, 1998, pp. 15–33.
Osborne CA, Stevens JB. Proteinuria. In: 
Urinalysis: A Clinical Guide to 
Compassionate Patient Care. Leverkusen, 
Germany: Bayer, 1999, pp. 111–121.
Author  Karen E. Russell
Consulting Editor  Benjamin M. BrainardUrinalysis Overview  (continued)1564  Blackwell’s Five-Minute Veterinary Consult

Canine and Feline, Seventh Edition  1565
Urine Sediment
  BASICS
Urine
• Microscopic evaluation of urine is 
recommended on every urine sample, even 
when physical characteristics or the results 
from a urine dipstick are unremarkable.
• Components evaluated include cells, 
crystals, casts, organisms, and other elements 
(e.g., lipid, mucus):
◦ Erythrocytes can enter the urine 
anywhere in the urologic tract (i.e., kidneys, 
ureters, bladder, urethra) or genital tract.
◦ Neutrophils are the common leukocyte 
found in urine, but macrophages and 
lymphocytes can also be present.
◦ Epithelial cells include renal tubular cells, 
transitional cells, and squamous cells. 
Neoplastic cells are sometimes detected.
◦ Formation of crystals depends on urine 
pH and concentration (i.e., urine specific 
gravity [USG]) and the presence of 
oversaturated crystalogenic substances.
▪ Diet and some drugs may also 
influence crystal formation.
▪ The presence of crystals suggests an 
increased risk of urolithiasis, but it does 
not predict which animals may actually 
form uroliths or the type of urolith that 
may form.
◦ Casts originate in the tubular lumen and 
are composed of mucoprotein, cells, and 
cellular debris. The presence of casts may 
indicate renal proteinuria (hyaline) or tubular 
degeneration (cellular and/or granular).
is part of a routine urinalysis (UA).
• Many of the chemical results (e.g., urine 
heme protein, protein) should be interpreted 
in conjunction with the sediment findings.
• Part of the workup in an animal exposed to 
a nephrotoxic substance or in those with 
stranguria or pollakiuria.
None
None
Urine sediment is critical in diagnosing 
• Renal and urologic.  SAMPLE
• 5–10 mL of urine collected by free catch of 
a voided sample, manual expression of the 
urinary bladder, catheterization, or cystocen-
tesis. The method of collection may affect 
sediment makeup.
• It is important that a consistent volume of 
urine is used for sediment evaluation. This will 
enable findings to be semiquantitative and 
compared with reference values, and enable 
monitoring of the animal’s response to treatment.
• Collect the urine into a clean container free 
of additives, detergents, and chemicals.
• Ideally, the assay should be performed 
within an hour after collection.
• Refrigeration can aid in slowing cellular 
breakdown, but it enhances crystal formation. 
If refrigerated, sample should be warmed to 
• Do not freeze the urine.
cells, casts, crystals, bacteria) do not hold up 
well in urine. Cells may lyse, and casts can break 
down. Crystals can dissolve or new crystals may 
form. Bacteria may die or multiply:
• Casts begin to deteriorate within 2 hours.
• Cells can lyse or lose morphologic 
characteristics within 2–4 hours, depending 
on urine osmolality.
PROTOCOL
• A standard volume of urine (usually 5 mL) 
is centrifuged at a slow speed.
• The supernatant is removed and saved for 
biochemical or other tests.
• The pellet is gently resuspended in a small 
amount of urine (≈1 mL), and a small drop is 
placed onto a glass slide with a coverslip.
• Microscopic examination is done at a low 
magnification (10× objective; low-power field 
[LPF]) and a high magnification (40× 
objective; high-power field [HPF]) with the 
condenser of the microscope lowered so that 
contrast is increased.
• Several components are quantified by the 
number per LPF (i.e., casts) or HPF (i.e., cells).
• Other components such as crystals, bacteria 
or other organisms, lipid, and mucus are 
either graded as present or absent or graded on 
a few (1+), moderate (2+), or many (3+) scale.
• Staining the urine sediment with a 
commercial, water-based stain or new 
methylene blue before examination may aid 
in identifying constituents and accentuate 
cellular detail.• A cytologic preparation of urine sediment 
can be made by smearing a drop of sediment 
on a slide, allowing it to air-dry, and staining 
it with routine hematologic stains. This 
technique is useful in evaluating cells and 
identifying bacteria or other organisms.
• Urine sediment is usually inactive, 
containing few microscopically visible 
components, but it is not uncommon to find 
low numbers of cells or certain types of 
crystals, depending on method of collection.
• The following may be seen in urine from 
healthy dogs or cats:
◦ WBCs: <2–5/HPF .
◦ RBCs: <2–5/HPF .
◦ Epithelial cells: <2/HPF .
◦ Casts: none or at most a few that are 
hyaline or granular.
◦ Crystals: amorphous phosphate, bilirubin 
(dogs), calcium oxalate dihydrate, calcium 
phosphate, and struvite are common in 
healthy animals. Ammonium biurate, sodium 
urates, and uric acid crystals are occasionally 
seen in urine from healthy animals.
◦ Bacteria: usually none. Low numbers 
occasionally are seen in voided samples with 
genital tract contamination or samples 
taken from floors, tabletops, or litterboxes.
◦ Sperm (intact males).
The following are considered abnormal in 
dogs or cats:
• WBCs: >5/HPF .
• RBCs: >5/HPF .
• Epithelial cells: >5/HPF .
• Casts: the presence of > 1–2/LPF (hyaline, 
granular) or any cellular (epithelial, RBC, 
WBC), waxy, fatty, and/or broad casts.
• Crystals: the presence of calcium oxalate 
monohydrate, ammonium biurate, bilirubin, 
cholesterol, cystine, leucine, tyrosine, sodium 
urate, and/or uric acid (see Table 1).
None
Acidifiers or alkalinizers may modify crystal 
formation and composition.
Sulfadiazine and metabolites, ampicillin, 
allopurinol, and radiopaque contrast agents

1566  Blackwell’s Five-Minute Veterinary Consult  
Table 1
ElementReference Interval With Lesion 
Location Etiology
Cells
RBCs (hematuria) <2–5/HPF
>5/HPF
RenalMay be normal
Bleeding or vascular damage associated with glomeruli or tubules, calculi, renal vein 
thrombosis, vascular dysplasia, trauma, infarct, inflammation, or infection
Lower urinary tract
Genital tract
CoagulopathyAcute or chronic infection, calculi, neoplasia, or hemorrhagic cystitis Voided urine sample 
from animals in estrus
Vessel damage from cystocentesis or catheterization
Thrombocytopenia, thrombocytopathia, von Willebrand disease, or hereditary or acquired 
coagulopathies
WBCs (pyuria) <2–5/HPF
>5/HPF
Inflammation from noninfectious causes: pyelonephritis/nephritis, urolithiasis (calculi), 
neoplasia, or necrosis
Inflammation from infectious causes: pyelonephritis/nephritis, bacteria, fungal, or 
parasitic
Genital tract inflammationAcute or chronic cystitis (infectious or noninfectious), calculi, neoplasia Voided urine 
sample with contamination from the prostate, prepuce, or vagina
Epithelial cells Squamous epithelial cells Insignificant finding in voided or catheterized samples
Transitional cells
<2/HPF
>5/HPFMay be normal or artifact of collection method
Hyperplasia secondary to inflammation, infection, or irritation, or due to cyclophosphamide 
administration
Neoplastic cells Transitional cell carcinoma cells occasionally found in urine; caution advised if cellular 
atypia noted in the presence of inflammation (may be difficult to differentiate 
hyperplasia from neoplasia)
Crystals  
(crystalluria)Type of crystal and typical 
conditionsEtiology
Urine pH acidic or neutral 
Amorphous urateFormed from yellow precipitates of sodium, potassium, magnesium, or calcium urate salts; 
normal in dalmatians and English bulldogs; also seen with liver disease or portal 
vascular anomalies
Bilirubin May be seen in healthy dogs, common in dogs with bilirubinemia or abnormal bilirubin 
metabolism, and uncommon in cats
Calcium oxalate monohydrate Common with ethylene glycol toxicosis
Calcium oxalate dihydrate Found in healthy dogs and cats, found in animals with uroliths composed mostly of calcium 
oxalate, and occasionally seen with ethylene glycol toxicosis
Cystine Rare; congenital renal tubular defect in reabsorption of cystine from the renal filtrate; 
cystinuria may result in cystine store for formation
Sodium urate
SulfaMay be seen concurrently with ammonium urate crystals Associated with sulfonamide 
Uric acid Considered normal in dalmatians and English bulldogs, rarely seen in other healthy animals, 
and can be seen with liver disease or portal vascular anomalies
Urine pH alkaline and/or neutral
Ammonium urate 
(ammonium biurate)Portosystemic shunts or hepatic diseases with hyperammonemia, can be seen rarely in 
healthy animals but are common in dalmatians and English bulldogs
Amorphous phosphate Amorphous form of calcium phosphate crystals that resemble amorphous urates; may be 
seen in healthy dogs and catsUrine Sediment  (continued)

Canine and Feline, Seventh Edition  1567
(continued)  Urine Sediment
Calcium phosphate Seen in healthy dogs and in dogs with persistently alkaline urine or with calcium 
phosphate uroliths
Struvite (triple phosphate) Common in cats and dogs with alkaline urine; composed of magnesium, ammonium, and 
phosphorus
Other crystals
Ampicillin
Leucine
Melamine
Tyrosine
XanthineAssociated with ampicillin administration
Uncommon; associated with cellular membrane deterioration, occasionally seen with some 
renal diseases, and may be seen in healthy dogs
Rare, ingestion of food contaminated with melamine
Rare; may suggest liver disease
Rare in dogs; can be associated with liver disease
Rare; may be seen in animals treated with allopurinol
Casts (cylinduria) Type of cast Etiology
Hyaline A few can be normal with concentrated urine; >1–2/LPF associated with renal causes of 
proteinuria
Cellular WBC Associated with tubular inflammation, infection (e.g., bacterial pyelonephritis, 
leptospirosis), or acute tubular necrosis
Epithelial Associated with degeneration/necrosis of tubules (e.g., ischemia, toxins, infarct)
RBC Rare; associated with hemorrhage into tubules
Granular A few can be normal with concentrated urine; >1–2/LPF associated with degeneration/
necrosis of tubules (e.g., ischemia, toxins, infarct)
Fatty Common in cats with renal tubular degeneration
Waxy Associated with chronic degeneration/necrosis of tubules (e.g., ischemia, toxins, infarct)
Bacteria 
(bacteriuria)Infection of the urinary tract, infection of the genital tract (voided sample), in vitro  growth with 
delayed sample analysis, or contamination (voided and some catheterized samples)
Other organisms Yeast
Fungi (hyphae or budding)
Nematode ova
Microfilariae
AlgaeOften Candida spp.
Blastomyces spp., Cryptococcus spp., or Aspergillus spp. (German shepherd dogs can have 
a disseminated infection)
Dioctophyma renale or Capillaria plica
Seen with significant hematuria
Prototheca spp. (dogs can have disseminated infection)
Lipids No clinical significance; may be normal; a common finding in cats
Mucus Genital secretions, suggestive of urethral irritation; mucous strands may form linear 
structures resembling casts
Contaminants Pollen grains
Sperm
Glove powder
FibersOccasionally found in urine sediment, not significant but may be potentially confused with 
other constituentsTable 1
Causes of abnormal findings ( Continued )

1568  Blackwell’s Five-Minute Veterinary Consult  
(uncommon) have been associated with 
crystal formation in dogs and cats.
• Casts and cells, especially RBCs, may lyse 
in poorly concentrated (USG <1.008) or 
alkaline urine, especially if a sample is several 
hours old.
• RBCs usually are crenated in highly 
concentrated urine. This may cause diffi -
culties with identification.
• Voided samples may contain more cells, 
have bacterial contamination, or contain 
material from the genital tract.
• Catheterized samples may contain more 
RBCs or epithelial cells (transitional or 
squamous cells) or be contaminated with 
lubricant.
• Samples obtained by cystocentesis generally 
have the least potential of contamination but 
may contain increased RBCs if blood vessels 
are damaged during urine collection. Inadvertant 
enterocentesis is uncommon but can occur.
• Refrigeration enhances crystal formation.
• The use of certain urine preservatives may 
cause in vitro formation of tyrosine-like 
crystals.
• The use of stain can dilute sediment, 
lowering counts, and may introduce crystals 
and/or organisms (i.e., bacteria, yeast) that 
grow in stain.
Species
• Lipid droplets are common in cats and are 
of no clinical significance.
• Low numbers of bilirubin crystals are 
sometimes seen in concentrated urine from 
healthy dogs.
• Cystinuria with cystine crystal formation is 
more common in dogs but occurs rarely in 
cats.
Breed
• Uric acid and ammonium biurate crystals 
are common in Dalmatians and English 
bulldogs.
• Cystinuria with cystine crystalluria has been 
reported in many breeds of dogs, including 
dachshunds, Newfoundlands, English 
bulldogs, Scottish deerhounds, mastiffs, and 
Scottish terriers.
Age
None
Gender
Sperm may be found only in the urine from 
intact males or recently bred intact females.
Pregnancy
NoneLIMITATIONS OF TEST
• Crystals that form in vitro  have no clinical 
• The number of casts is not an indication of 
the severity, duration, or potential reversibil-
ity of the underlying disease. The type of cast 
rarely denotes a specific diagnosis.
• A normal sediment does not rule out some 
type of urinary tract disease.
N/A
Yes.
• Urine sediment examination should always 
be part of a routine UA, even if physical and 
chemical characteristics are unremarkable.
• A standard volume of urine used for 
sediment examination should be established.
• Chemistry results (e.g., heme protein, 
protein) should be interpreted with knowl-
edge of urine sediment.
• The urine pH can affect the type of crystals 
present, and the USG can affect urine 
sediment.
• The presence of crystals does not necessarily 
indicate the presence of a urolith, although 
high concentrations of crystals may predis-
pose an animal to urolith formation. Clinical 
signs and hematuria may help identify those 
animals with uroliths.
• Cocci are difficult to identify unless in 
chains: Brownian movement of tiny particles 
of debris may resemble cocci. Suspected cocci 
should be verified by Gram staining an air-dried 
smear of sediment. Cocci will appear deep 
purple with a Gram stain, whereas debris/
protein will be pink or perhaps colorless.
• Some sediment abnormalities (e.g., casts) 
can be an early sign of nephrotoxicity seen 
prior to the onset of serum chemistry 
• The absence of pyuria or a failure to detect 
bacteria does not exclude an occult urinary 
tract infection. This is particularly common 
in conditions associated with dilute urine, 
such as diabetes mellitus and 
• Serum biochemical profile.
• CBC.
• UA (including heme, protein, USG, pH).• Urine culture.
• Urolith analysis.
• CadetBRAF assay (Antech diagnostics): if 
urinary tract neoplasia is suspected.
SYNONYMS
None
SEE ALSO
• Cylindruria.
• Pyuria.
• HPF = high-power field (40×).
• LPF = low-power field (10×).
cellular-constituents/
• http://www.meddean.luc.edu/lumen/
meded/medicine/pulmonar/renal/atlas/
urineatlas_f.htm
Chew DJ, DiBartola SP . Interpretation of 
Canine and Feline Urinalysis. Wilmington, 
DE: Ralston Purina, 1998.
Graff L. A Handbook of Routine Urinalysis. 
Philadelphia, PA: J.B. Lippincott Company, 
1982.
Meyer DJ. Microscopic examination of the 
urinary sediment. In: Raskin RE, Meyer DJ, 
eds., Canine and Feline Cytology, 3rd ed. 
St. Louis, MO: Elsevier, 2016, pp. 
295–312.
Mochizuki H, Shapiro SG, Breen M. 
urothelial and prostatic carcinoma. PLoS 
Osborne CA, Stevens JB. Urine sediment: 
under the microscope. In: Urinalysis: A 
Clinical Guide to Compassionate Patient 
Care. Leverkusen, Germany: Bayer, 1999, 
pp.125–179.
Webb JL. Renal cytology and urinalysis. In: 
Small Animal Cytologic Diagnosis. Boca 
Raton, FL: CRC Press, 2017, pp. 357–377.
Consulting Editor  Benjamin M. BrainardUrine Sediment  (continued)

Canine and Feline, Seventh Edition  1569
Conversion TablesAppendix xi
Table XI-A
Conversion table of weight to body surface area (in square meters) for dogs
kg m2kg m2
0.5 0.06 26.0 0.88
1.0 0.10 27.0 0.90
2.0 0.15 28.0 0.92
3.0 0.20 29.0 0.94
4.0 0.25 30.0 0.96
5.0 0.29 31.0 0.99
6.0 0.33 32.0 1.01
7.0 0.36 33.0 1.03
8.0 0.40 34.0 1.05
9.0 0.43 35.0 1.07
10.0 0.46 36.0 1.09
11.0 0.49 37.0 1.11
12.0 0.52 38.0 1.13
13.0 0.55 39.0 1.15
14.0 0.58 40.0 1.17
15.0 0.60 41.0 1.19
16.0 0.63 42.0 1.21
17.0 0.66 43.0 1.23
18.0 0.69 44.0 1.25
19.0 0.71 45.0 1.26
20.0 0.74 46.0 1.28
21.0 0.76 47.0 1.30
22.0 0.78 48.0 1.32
23.0 0.81 49.0 1.34
24.0 0.83 50.0 1.36
25.0 0.85
Table XI-B
Approximate equivalents for degrees Fahrenheit and Celsius*
°F °C °F °C
  0 –17.8 98 36.7
32 0 99 37.2
85 29.4 100 37.8
86 30.0 101 38.3
87 30.6 102 38.9
88 31.1 103 39.4
89 31.7 104 40.0
90 32.2 105 40.6
91 32.7 106 41.1
92 33.3 107 41.7
93 33.9 108 42.2
94 34.4 109 42.8
95 35.0 110 43.3
96 35.5 212 100.0
97 36.1Although the above chart was compiled for dogs, it can also be used for cats. More precise values are represented in the formula BSA in m2 = (K × W2/3) × 10–4; where 
m2 = square meters, BSA = body surface area, W = weight in g, and K = constant of 10.1 in dogs and 10.0 in cats.
* Temperature conversion: °  Celsius to °  Fahrenheit, (°  C) (9/5) + 32°; °  Fahrenheit to °  Celsius, (°  F – 32°) (5/9).

1570  Blackwell’s Five-Minute Veterinary Consult  
Table XI-C
Weight-unit conversion factors
Units Given Units Wanted For Conversion, Multiply by
lb g 453.6
lb kg 0.4536
oz g 28.35
kg lb 2.2046
kg mg 1,000,000
kg g 1000
g mg 1000
g μg 1,000,000
mg μg 1000
mg/g mg/lb 453.6
mg/kg mg/lb 0.4536
μg/kg μg/lb 0.4536
Meal kcal 1000
kcal/kg kcal/lb 0.4536
kcal/lb kcal/kg 2.2046
ppm μg/g 1
ppm mg/kg 1
ppm mg/lb 0.4536
mg/kg % 0.0001
ppm % 0.0001
mg/g % 0.1
g/kg % 0.1Conversion Tables ( continued )

Canine and Feline, Seventh Edition  1571
Important Resources for Veterinarians
ACCREDITATION
• National Veterinary Accreditation Program; www.aphis.usda.gov/nvap
ADVERSE EVENT REPORTING
Submit reports of adverse events associated with animal foods or health products as well as suspected failures of animal health products to the 
manufacturer and one of the following:
• Drugs and devices: FDA CVM: 888-332-8387; www.fda.gov/AnimalVeterinary
• Pet foods and animal feeds: FDA consumer complaint coordinators; www.fda.gov/Safety/ReportaProblem/ConsumerComplaintCoordinators
• Topical insecticides: National Pesticide Information Center (sponsored by EPA): 800-858-7378; www.npic.orst.edu
• Vaccines/biologics: USDA Center for Veterinary Biologics: 800-752-6255; bit.ly/VetBiologics
ANIMAL DRUGS
• FDA CVM: 240-276-9300; askcvm@fda.hhs.gov; www.fda.gov/drugs; Report shortages of medically necessary veterinary drugs.
• Food Animal Residue Avoidance Databank: 888-873-2723; www.farad.org
Information on animal drugs and chemicals with the potential to cause foodborne residues (sponsored by the USDA Cooperative State Research, 
Education and Extension Service)
BLOOD BANKS, RESOURCES
• Animal Blood Resources International: 800-243-5759; www.abrint.net
A 24-hour hotline focusing on transfusion medicine (particularly blood component therapy), including recommended dosages and infusion rates for 
canines and felines; no cost to caller
• HEMOPET: 714-891-2022; www.hemopet.org
A 24-hour national, non-emergency, full service, nonprofit blood bank and educational network for animals
• Plasvacc USA: 805-434-0321; www.plasvaccusa.com
A commercial blood bank for canines and equines
• Veterinarians Blood Bank: 877-838-8533; www.vetbloodbank.com
A commercial blood bank for canines and felines
• Association of Veterinary Hematology and Transfusion Medicine: www.avhtm.org
Additional resources and links
CONTROLLED DRUGS
• DEA Office of Diversion Control; registration: 800-882-9539; www.deadiversion.usdoj.gov
DISASTER AND EMERGENCY RESPONSE
• FEMA Disaster Assistance: 800-621-3362; www.fema.gov
DISEASE OUTBREAKS
• USDA APHIS Emergency Operations Center: www.aphis.usda.gov/emergencyresponse
Report suspected animal disease outbreaks
• CDC Emergency Operations Center: 800-323-4636; www.cdc.gov/phpr/eoc.htm
• State veterinarians: www.usaha.org/federal-and-stateanimal-health
• State public health veterinarians: http://www.nasphv.org/Documents/StatePublicHealthVeterinariansByState.pdf
FOOD SAFETY
• FDA: 888-463-6332;; www.fda.gov/food
• USDA FSIS: 202-720-9113; www.fsis.usda.gov
• USDA Meat and Poultry Hotline: 888-674-6854; bit.ly/USDAhotline
• American College of Veterinary Nutrition: http://www.acvn.org
• World Small Animal Veterinary Association nutrition toolkit: https://www.wsava.org/nutrition-toolkit
IMPAIRED VETERINARIANS AND VETERINARY TECHNICIANS
•  Impaired Veterinarians Resources (sponsored by the AVMA): 800-248-2862, Ext. 6738; https://www.avma.org/ProfessionalDevelopment/
PeerAndWellness/Pages/default.aspxAppendix XII

1572  Blackwell’s Five-Minute Veterinary Consult  
PET LOSS SUPPORT—GRIEF COUNSELING
• Chicago VMA: 630-325-1600; https://www.chicagovma.org/pet-losssupport/
• Colorado State University, Argus Institute: 970-297-1242; www.argusinstitute.colostate.edu
• Cornell University: 607-253-3932; https://www.vet.cornell.edu/about-us/
outreach/pet-loss-support-hotline
• University of Illinois: 217-244-2273 or 877-394-2273; https://vetmed.illinois.edu/animal-care/care-pet-loss-helpline/
• Michigan State University: 517-432-2696; https://cvm.msu.edu/hospital/services/social-work/pet-loss-support-group
•  University of Pennsylvania: 215-898-4556; https://www.vet.upenn.edu/veterinaryhospitals/ryan-veterinary-hospital/services/
grief-support-social-services
• University of Tennessee: 865-755-8839; https://vetsocialwork.utk.edu/grief-andbereavement/
• Tufts University: 508-839-7966; https://vet.tufts.edu/petloss/
• Washington State University: 509-335-5704 or 866-266-8635; https://apps.vetmed.wsu.edu/PetMemorial/Home
POISON CONTROL
• American Association of Poison Control Centers: 800-222-1222; www.aapcc.org
• ASPCA Animal Poison Control Center: 888-426-4435; www.aspca.org/apcc
Small fee per case for veterinarians enrolled in the Veterinary Life Line Partner Program; no charge for calls covered by ASPCA Animal Product Safety Service
• Pet Poison Helpline: 855-764-7661; www.petpoisonhelpline.com
24-hour, nationwide service offered by the Pet Poison Control Center; small fee charged
SHIPPING
Animals
•   CDC: 800-232-4636; https://www.cdc.gov/importation/bringing-an-animal-into-the-unitedstates/index.html
For information about importing animals into the United States
• USDA APHIS Veterinary Services: 301-851-3300; bit.ly/USDAVetServices
Specimens
• Department of Transportation, Office of Hazardous Materials: 800-467-4922; www.phmsa.dot.gov/hazmat
WORKPLACE SAFETY
• OSHA: 800-321-6742; www.osha.gov
Compiled by the Publications Division, American Veterinary Medical Association (AVMA). Phone numbers current as of November 2019. Modified from JAVMA.Important Resources for Veterinarians ( continued )

1573Note: text in boldface denotes chapter discussions.
5‐fluorouracil (5‐FU) toxicosis , 1
A
A‐lines, 1544
AB blood group system, feline, 1498, 
1499– 1500
ABCB1  gene mutation. See MDR1/
ABCB1  gene mutation
Abdomen, acute , 18–20
Abdominal point of care 
ultrasonography , 1538–1540
Abdominocentesis and fluid analysis , 
1476–1478
Abdominocentesis (paracentesis), 
therapeutic, 121, 703
Aberdeen terrier, dystocia, 428
Abortion , 2–7
spontaneous
in cats, 2–3
in dogs, 4–5
termination of pregnancy, 6–7
Abrus precatorius,  1456
Abscessation , 8–9
anal sac, 9, 77
hepatic, 630–631
orbital, 1001, 1002, 1325
prostatic, 1132–1133
tooth root, 1343–1344
Abyssinian cat
aggression, 56
amyloidosis, 74, 308, 609
anemia, 90
aortic thromboembolism, 108
atopic dermatitis, 134
blood type, 1499, 1512
chronic kidney disease, 274
hyperesthesia syndrome, 503
hypothyroidism, 747
myasthenia gravis, 920
paresis/paralysis, 930
pyruvate kinase deficiency, 1171
retinal dysplasia, 310, 1193
stomatitis, 519, 1297
Acarbose, 398
Acaricides. See also  Insecticides
for tick control, 437, 1337, 1339
Accreditation, 1571ACE inhibitors. See Angiotensin‐
converting enzyme inhibitors
Acemannan, 507, 515
Acepromazine, 1449
for amphetamine toxicosis, 73
for antidepressant toxicosis, 102, 105
for aortic thromboembolism, 110
for baclofen toxicosis, 163
for benzodiazepine/sleep aid 
toxicosis, 170
for car ride anxiety, 221
for chocolate toxicosis, 261
for epistaxis, 460
for excessive vocalization, 477
for feline asthma and bronchitis, 128
for head tilt, 584
for hereditary Scottie cramp, 946
for illicit/club drug toxicosis, 758
for maternal behavior problems, 878
for pseudoephedrine/phenylephrine 
toxicosis, 1144
for stertor and stridor, 1296
for tetanus, 1320
for thrombocytopenia, 1328
for thunderstorm and noise phobias, 
1333
for tracheal collapse, 1349
for urinary retention, 1366–1367
for ventricular arrhythmias, 1409, 
1417
for vestibular disease, 1422, 1424
for veterinary visits, 491, 493
Acetaminophen, 1467
for osteoarthritis, 1471
for osteosarcoma, 1012
for spondylosis deformans, 1281
for syringomyelia and Chiari‐like 
malformation, 1313
Acetaminophen (APAP) toxicosis , 
10–11, 83
Acetazolamide
for caudal occipital malformation 
syndrome, 1276
for hydrocephalus, 664
for quadrigeminal cyst, 1177
for syringomyelia, 1313
Acetic acid, for otitis externa, 1014
Acetohydroxamic acid (AHA), 1382Acetone toxicosis, 1464
Acetylcysteine. See N‐acetylcysteine
Acetylsalicylic acid. See Aspirin
Achilles mechanism injuries, 914, 915
Achondroplasia, 1006
Achromatopsia, 310
Aciclovir, 502
Acid burns, 1461
Acid maltase deficiency (Pompe’s 
disease), 573, 948
Acidosis, metabolic , 12–13
Acitretin, 858, 1284, 1288
Acne , 14–15
in cats, 14, 380–381
in dogs, 15, 380–381
papulonodular dermatosis, 380–381
Aconitum  spp., 1455
Acotiamide, 549
Acquired portosystemic shunting. See 
Portosystemic shunting, acquired
Acral lick dermatitis , 16
Acromegaly (ACM), 900, 901
Acromegaly in cats , 700
Actea  spp., 1452
ACTH (corticotropin)
excess, 668, 671
insufficiency, 719
reference ranges, 1445
stimulation test, 1444
Actinic keratosis, 384
Actinomycosis , 17
cutaneous, 980
Activated charcoal, 1098
for acetaminophen toxicosis, 11
for aspirin toxicosis, 126
for beta receptor antagonist 
toxicosis, 171
for blue‐green algae toxicosis, 187
for bromethalin rodenticide toxicosis, 
1208
for calcipotriene/calcipotriol 
toxicosis, 204
for calcium channel blocker 
toxicosis, 205
for cardiac glycoside plant 
toxicosis, 225Index

1574  Index  
for cholecalciferol rodenticide 
toxicosis, 1210
for essential oils toxicosis, 472
for fipronil toxicosis, 535
for flatulence, 537
for 5‐fluorouracil toxicosis, 1
for grape and raisin toxicosis, 577
for lily toxicosis, 834
for neonicotinoid toxicosis, 968
for NSAID toxicosis, 981
for opiate/opioid toxicosis, 997
for organophosphorus and carbamate 
toxicosis, 1004
for pyrethrin/pyrethroid toxicosis, 1170
for sago palm toxicosis, 1213
Acupuncture, 649, 786
Acute abdomen , 18–20
Acute canine idiopathic 
polyradiculoneuritis (ACIP), 
326–327
Acute hemorrhagic diarrhea syndrome , 
554–555
Acute hepatic failure , 614–616
Acute kidney injury (AKI) , 23–24
drug‐induced, 974–975
in grape and raisin toxicosis, 577
Acute pain , 1021–1024
Acute respiratory distress syndrome 
(ARDS) , 25–26
ADAMTS17  gene, 827
Adaptil
for fear and anxiety, 492, 497, 1233
for puppy behavior problems, 1156, 
1158
ADD/ADHD medication toxicosis , 
72–73
Adderall. See Amphetamine toxicosis
Addisonian crisis, acute, 720
Addison’s disease , 719–721
Adenocarcinoma , 29–41
anal sac, 29–30, 77
ceruminous gland, ear, 251
large intestine, 39
lung, 31
nasal, 32–33
pancreas, 34
prostate, 35
rectal, 39
renal, 36
salivary gland, 37
skin (sweat gland, sebaceous), 38
small intestine, 39
stomach, 39
thyroid (in dogs), 40–41Adenosine, 1308
S‐Adenosylmethionine. See 
S‐adenosylmethionine
Adequan. See Polysulfated 
glycosaminoglycans
Adipex‐P . See Phentermine toxicosis
Adonis  spp., 1453
Adrenal insufficiency. See 
Hypoadrenocorticism
Adrenal tumors, hyperadrenocorticism, 
667, 668, 671
Adrenalin. See Epinephrine
Adrenocortical hyperplasia, 667, 668
Adrenocorticotropic hormone. See 
ACTH
Adriamycin. See Doxorubicin
Advanced life support, 244
Adverse event reporting, 1571
Adverse food reactions. See Food 
reactions, adverse
Aelurostrongylus abstrusus,  1092, 1093, 
1190–1191, 1523
Aerophagia, 536
Aesculus  spp., 1454
Affective aggression, in dogs, 58
Affenpinscher, syringomyelia and 
Chiari‐like malformation, 1312
Afghan hound
chylothorax, 277
corneal dystrophy, 337
hair follicle tumors, 578
lung lobe torsion, 843
myocardial tumors, 934
sexual development disorders, 1238
testicular tumors, 779, 1230, 1237
Aflatoxin toxicosis , 926
Afoxolaner, 538, 1221
Aggression , 42–61
in cats, 56–57
defensive, 56
fear‐related, 49, 53, 56
frustration‐related, 56
to humans, 49–50, 56
impulse control, 56
intercat, 53–55, 56
intermale, 53
kittens, 801–802
maternal, 49, 53, 56
pain‐related, 49, 54, 56
petting/contact intolerance,  
49, 56
play‐related, 49, 56
predatory, 54, 56
recognition failure‐related, 53
redirected, 49, 53, 56
sexual, 53–54
status‐related, 53
territorial, 53, 56
in veterinary visits, 490–491in dogs, 58–60
affective (emotional), 58
to children, 46
conflict (dominance), 58
to familiar/other household dogs, 
42–43
to familiar people, 47–48, 58
fear‐related, 44, 58
food and resource guarding, 51–52
human‐directed, 44–48, 58
play‐related, 58
predatory, 58
puppies, 1155
territorial, 44, 58
to unfamiliar people/dogs, 
44–45, 58
in veterinary visits, 492–493
Agkistrodon  spp. envenomation, 
1266–1267
Aglaonema commutatum,  775
for acromegaly, 901
for gestational diabetes mellitus, 561
for mammary gland hyperplasia, 864
for pyometra, 1166
for termination of pregnancy, 7
for vaginal discharge, 1392
Air plant, 1452
Airedale terrier
atrioventricular block, 152
cerebellar hypoplasia, 130, 248, 689
flank alopecia, 67
glomerulopathy, 308
lymphoma, 851, 856
melanocytic tumors, 888
pancreatic carcinoma, 34
spondylosis deformans, 1281
vaginal hyperplasia and prolapse, 
1393, 1394
vomiting, 1426
von Willebrand disease, 459, 1429
Airway collapse, 1348
Airway obstruction, 1295, 1296. See also  
Brachycephalic airway syndrome
Akita
alopecia X, 67, 68, 69
blood smear examination, 1494
gastric dilation and volvulus 
syndrome, 546
hepatic amyloid, 609, 610
metabolic myopathy, 946
pemphigus foliaceus, 372, 385, 1055
polyarthritis, 1103
pseudohyperkalemia, 683
retinal disease, 1193
sebaceous adenitis, 376, 1224
thrombocytopenia, 1327Activated charcoal ( cont’d )

Index  1575
uveodermatologic syndrome, 100, 
272, 372, 956, 1390
ventricular septal defect, 1411
von Willebrand disease, 1429
Alaria  spp., 1523
Alaskan malamute
depigmenting dermatoses, 372
exfoliative dermatoses, 376
glaucoma, 564
interstitial pneumonia, 1092
leishmaniosis, 825
leukocytosis, 831
lupus erythematosus, 844
nasal dermatoses, 956
osteochondrodysplasia, 900, 1006
ovulatory failure, 1020
polyneuropathies, 1107
renal dysplasia, 274, 308
retinal degeneration, 310, 1193
skin tumors, 378
stertor and stridor, 1295
uveodermatologic syndrome, 1390
zinc‐responsive dermatosis, 182
for baylisascariasis, 167
for giardiasis, 562
for Pearsonema  infection, 1371
for respiratory parasites, 1191
Albinism, 372
Albuterol (salbutamol)
for anaphylaxis, 79
for cough, 340
for hyperkalemia, 683
for hypoxemia, 751
toxicosis, 172
Alcohol (ethyl alcohol). See Ethanol
Alcohols, toxic exposures, 1464
Aldosterone, plasma, 1445
Alendronate, 901
Alfaxalone, for veterinary visits, 491, 493
Alkaline battery toxicosis, 166
Alkaline hyperphosphatasemia in 
dogs , 61–62
Alkalis, strong, exposure, 1462
Alkalosis, metabolic , 63–64
Allergic blepharitis, 182, 183
Allergic conjunctivitis, 321, 322, 325
Allergic dermatitis, 134–135. See also  
Contact dermatitis
alopecia, 65, 66, 67
feet, 1096–1097
food reactions, 540
Allergy testing, 134
Allomarking, artificial, for intercat 
aggression, 54Allopurinol
induced xanthinuria, 971, 1385
for leishmaniosis, 824, 826
for urate urolithiasis, 971, 1383
Aloe, 1452
Alopecia , 65–70
canine flank/seasonal/cyclic, 67
canine multifocal, 67
canine symmetric, 67
in cats, 65–66
color mutant/dilution, 67, 376
in dogs, 67–70
feline paraneoplastic, 66, 518, 1043
feline symmetrical, 521
noninflammatory, in dogs, 67, 68, 
69–70
paraneoplastic, 66, 1043
pinnal, 67, 68
post‐clipping, 67
psychogenic, 66, 304–305
traction, 65, 67
Alopecia areata, 65, 67
Alopecia universalis, 65
Alopecia X, 67, 68, 69–70
Alpha‐1 adrenergic agonists, for 
functional urinary retention, 
1366
Alpha‐2 adrenergic agonists. See also  
Clonidine; Dexmedetomidine
for canine aggression, 43, 45, 48
for fears, phobias, and anxieties, 497
1333–1334
Alpha‐2 adrenergic antagonists, for 
imidazoline toxicosis, 759
Alpha‐adrenergic agonists, for urinary 
incontinence, 766, 1054
Alpha‐blockers (alpha‐adrenergic 
receptor antagonists)
for hydronephrosis, 665
for hypertension, 707
for pheochromocytoma, 1077
for vertebral column trauma, 1420
Alpha‐casozepine (Zylkene)
for canine aggression, 43, 45, 46, 
48, 60
for fears, phobias, and anxieties, 
495, 497
for feline aggression, 50, 55, 57
for kitten behavior problems, 
802, 804
for marking behavior, 871, 873
for puppy socialization problems, 
1158
Alprazolam
for destructive behavior, 390
for excessive vocalization, 477for fears, phobias, and anxieties, 495, 
497
for feline aggression, 50
for marking, roaming, and mounting 
behavior, 873
for separation anxiety syndrome, 1233
1333
for veterinary visits, 493
Altrenogest
for premature labor, 1126
for spontaneous abortion, 3, 5
Aluminum carbonate, for 
hyperphosphatemia, 699
Aluminum hydroxide
for calcipotriene/calcipotriol toxicosis, 
204
for hyperphosphatemia, 699
for iron toxicosis, 791
for renal secondary 
hyperparathyroidism, 696
Alveolar interstitial syndrome (AIS), 
1546
Alveolar mucositis, 519, 1297
Alveolar osteitis, feline , 498
Alveolar process fractures, 1353
Amanita  mushroom poisoning, 916–919
Amantadine
for cerebellar degeneration, 247
for neuropathic pain, 1468
for osteoarthritis, 116, 1469
for polyarthritis, 1102
Amaryllis  spp., 1452
Amblyomma americanum,  356, 436, 
1336, 1338
Amblyomma cajennense,  1204
Amblyomma maculatum,  645, 1336, 
1338
Amblyomma phagocytophilum,  436
Amblyomma platys,  436
Ameloblastic fibro‐odontoma (AFO), 
990
Ameloblastoma , 71, 988
canine acanthomatous (CAA), 988, 
989
Amelogenesis imperfecta, 409, 1342
American bulldog
lysosomal storage disease, 859
retinal degeneration, 1193
American cocker spaniel. See also  Cocker 
spaniel
aggression toward children, 46
anal sac disorders, 77
anemia, 90
atrioventricular block, 148, 152
cryptococcosis, 344
dilated cardiomyopathy, 232, 233, 
239, 240

1576  Index  
encephalitis, 442
glycogen storage disease, 573, 948
hemoglobinuria, 604
phosphofructokinase deficiency, 1078
prolapsed gland of third eyelid, 1127
thrombocytopathy, 1327
American Eskimo
methemoglobinemia, 904
transitional cell carcinoma, 1350
American foxhound, 
glomerulonephritis, 566
American hairless terrier, 67
American pit bull terrier. See also  Pit bull 
terrier
babesiosis, 161
cone rod dystrophy, 310
cystinuria, 308
parvovirus infection, 217
1393, 1394
American shorthair cat
hypertrophic cardiomyopathy, 235
nephrolithiasis, 970
American Staffordshire terrier. See also  
Staffordshire bull terrier
cerebellar degeneration,  
247, 689
demodicosis, 362
sun‐induced dermatoses, 384
American trypanosomiasis , 254
American water spaniel, alopecia,  
67, 68
Amikacin
for canine infectious respiratory 
disease, 216
for colibacillosis, 299
for peritonitis, 1070
for sepsis and bacteremia, 1236
for staphylococcal infections, 1293
for urinary tract infections, 839
Amino acid supplements
for glucagonoma, 569
for hepatocutaneous syndrome, 
634–635
for superficial necrolytic 
dermatitis, 1306
Aminocaproic acid ( ε‐aminocaproic 
acid), 288, 1244, 1328Aminoglycosides. See also  Amikacin; 
Gentamicin; Paromomycin
for corneal and scleral lacerations, 335
for endocarditis, 446
toxicity, 974, 975, 1424
Aminophylline, 79
Amiodarone
for dilated cardiomyopathy, 234
for ventricular arrhythmias, 1406, 
1410, 1417
Amitraz
for cheyletiellosis, 257
for demodicosis, 363
toxicosis, 363
Amitriptyline
for acral lick dermatitis, 16
for atopic dermatitis, 135
for compulsive disorders, 305, 307
for feline aggression, 49–50, 55, 57
for feline idiopathic lower urinary 
tract disease, 505
for feline symmetrical alopecia, 521
for housesoiling, 659
for marking, roaming and mounting 
for osteoarthritis, 1469
Amlodipine
for atrial wall tear, 145
for cerebrovascular accident, 250
for chronic kidney disease, 275
for congestive heart failure, 316
for glomerulonephritis, 567
for hypertension, 75, 460, 707
for hypertensive retinopathy, 1196, 1198
Ammonium tetrathiomolybdate, 330
Ammonium urate crystalluria, 348, 349
Amorphous urate crystalluria, 348, 349
Amoxicillin
for abscessation, 9
for actinomycosis, 17
for aspiration pneumonia, 1399
for clostridial enterotoxicosis, 285
for colitis and proctitis, 301
for dermatophilosis, 369
for feline calicivirus infection, 500
for feline herpesvirus infection, 502
for feline upper respiratory 
infections, 525
for Helicobacter  infection, 592
for hepatic encephalopathy, 417, 
612, 615
for Lyme borreliosis, 848
for mastitis, 876for pneumonia, 1087
for streptococcal infections, 1299
for tularemia, 1359
Amoxicillin‐clavulanic acid (Clavamox; 
Clavaseptin)
for anaerobic infections, 76
for anal sac disorders, 77
for bacterial folliculitis, 386
for bronchiectasis, 198
for chlamydiosis in cats, 258
for cholangitis/cholangiohepatitis 
syndrome, 263
for discospondylitis, 412
for dyschezia and hematochezia, 420
for eosinophilic granuloma 
complex, 452
for laryngeal and tracheal 
perforation, 811
for mastitis, 876
for metritis, 906
for neonatal sepsis, 966
for otitis, 584, 1014, 1016
for pneumonia, 1087
for pyoderma, 1163
for pyothorax, 1169
for spontaneous abortion, 3
for stomatitis, 1298
for suppurative hepatitis/hepatic 
abscess, 630
for tooth root abscess, 1344
for vestibular disease, 1423, 1424
Amoxicillin‐sulbactam, for acute 
hemorrhagic diarrhea 
syndrome, 555
Amphetamine toxicosis , 72–73
Amphimerus pseudofelineus,  836
for aspergillosis, 123
for blastomycosis, 181, 361
for coccidioidomycosis, 293
for colitis and proctitis, 301, 302
for cryptococcosis, 345, 361
for histoplasmosis, 654
for pneumonia, 1091
for protothecosis, 1141
toxicity, 181
for urinary tract infections, 840American cocker spaniel ( cont’d )

Index  1577
for acute hepatic failure, 615
for central nervous system infections, 
895
for laryngeal and tracheal perforation, 
811
for leptospirosis, 829
for near drowning, 415
for neutropenia, 979
for orbital abscess/cellulitis, 1002
Ampicillin–sulbactam
for aspiration pneumonia, 1085
for epididymitis and orchitis, 453
for gastrointestinal obstruction, 560
for pancreatitis, 1030
Amprolium, 294
Amyloid‐producing odontogenic tumor 
(APOT), 988, 989
Amyloidosis , 74–75
cutaneous, 382, 383
familial shar‐pei fever. See Shar‐pei 
fever, familial
hepatic, 609–610
renal, 74–75, 308
Anaerobic infections , 76
Anagen defluxion, 67
Anal prolapse , 1180
Anal sac abscessation, 9, 77
Anal sac adenocarcinoma ,  
29–30, 77
Anal sac disorders , 77
Analgesics, 1022–1023
for acute abdomen, 19
adjunctive, 1023, 1468
for atlantoaxial instability, 133
for battery toxicosis, 166
for craniomandibular osteopathy, 341
for discospondylitis, 412doses and indications, 1465–1468
for esophageal pain, 470
for hypertrophic osteodystrophy, 712
for intervertebral disc disease, 
782, 786
for lameness, 808
for neck and back pain, 962
for osteoarthritis, 1469–1470
for osteochondrodysplasia, 1006
for osteochondrosis, 1008
for pancreatitis, 1028, 1030
for polyarthritis, 1102, 1104
for shoulder problems, 1249
for urinary tract obstruction, 1369
Anaphylaxis , 78–79
blood transfusion reactions, 186
peripheral edema, 1066
Anaplasmosis , 436–437
Anatoxins, 187
Ancylostoma braziliense,  655
Ancylostoma caninum,  655, 1523
Ancylostoma tubaeforme,  655, 1523
Ancylostomiasis , 655
Andersen disease (glycogen branching 
enzyme deficiency), 573, 948
Andersonstrongylus milksi,  1190–1191
Androgen excess. See Hyperandrogenism
Androgen insensitivity, complete and 
partial, 1238
Anemia , 80–91
aplastic, 82
of chronic kidney disease, 80–81, 
87, 88
in 5‐fluorouracil toxicosis, 1
Heinz body, 83
hemolytic. See Hemolytic anemia
immune‐mediated, 84–85
of inflammatory disease, 87
iron‐deficiency, 86, 87, 88
nonregenerative, 87–88
nuclear maturation defects 
(megaloblastic), 89
regenerative, 90–91
for cesarean section, 429
hypercapnia, 674, 675
sinus bradycardia, 1257
Angioedema, 350
Angiostrongylosis
nasal, 959
neural, 444Angiostrongylus vasorum,  250, 1092, 
1093, 1190–1191
Angiotensin‐converting enzyme (ACE) 
inhibitors
for atrial standstill, 143
for atrioventricular valvular 
stenosis, 157
for congestive heart failure, 121, 
316, 318
for dilated cardiomyopathy, 233, 234
for familial shar‐pei fever, 488
for hypertension, 460, 707
for hypertrophic cardiomyopathy, 236, 
237
for myxomatous mitral valve disease, 
952
for nephrotic syndrome, 973
nephrotoxicity, 974
for patent ductus arteriosus, 1050
for proteinuria, 1139
for restrictive cardiomyopathy, 242
Angiotensin receptor blockers (ARBs)
for cirrhosis and fibrosis of liver, 281
Anidulafungin, 123
Animal drugs, 1571
Anion gap, 12–13
Anionic detergents, 1460
Anisocoria , 92–93
Anodontia, total and partial, 1341
Anophthalmos, 310
Anorexia , 94–95
Antacids
for gallbladder mucocele, 545
for gastroduodenal ulceration, 553
for rodenticide toxicosis, 1211
Antebrachial growth deformities , 
96–97
Anterior uveitis , 98–101
anisocoria, 92
cataracts, 245
in cats, 98–99
in dogs, 100–101
for bronchitis in cats, 128
for canine infectious diarrhea, 214
for chronic gastritis, 551
for diarrhea, 22
for eosinophilic gastroenteritis, 557

1578  Index  
for feline infectious diarrhea, 509
for hookworms, 655
for Ollulanus  infection, 993
for rhinitis and sinusitis, 1200
for roundworms, 1212
for tapeworms, 1317
for whipworms, 1435
Anthurium  spp., 775
Anti‐inflammatory agents. See also  
Corticosteroids; Nonsteroidal 
anti‐inflammatory drugs
for cataracts, 246
for colitis and proctitis, 301, 303
for fecal incontinence, 764
for immunoproliferative enteropathy 
of Basenjis, 762
for intervertebral disc disease, 782
for pulmonary hypertension, 705
Antiarrhythmic drugs
toxicosis, 225
for cardiomyopathies, 227, 230, 
233–234
for ventricular arrhythmias, 
1308, 1410
Antibiotic‐responsive diarrhea (ARD) , 
402. See also  Small intestinal 
dysbiosis
for acne, 14, 15, 381
for actinomycosis, 17, 980
for acute abdomen, 20
for antibiotic‐responsive diarrhea, 402
for babesiosis, 161–162
for bartonellosis, 164
for bile duct obstruction, 175
for bile peritonitis, 177
for blepharitis, 183
for brucellosis, 203, 412
for campylobacteriosis, 206
for canine distemper, 212
disease, 216for central nervous system 
infections, 895
for cholecystitis and choledochitis, 266
for cholelithiasis, 268
for chronic bronchitis, 201
for chronic vomiting, 1427
for claw and clawfold disorders, 
282, 283
for conjunctivitis, 320, 322
for corneal opacities, 336
for corneal sequestrum, 338, 797
for encephalitis, 443
for entropion, 449
for epiphora, 457
for exocrine pancreatic 
insufficiency, 481
for feline panleukopenia, 517
for feline stomatitis, 519
for fever, 527
for gastric dilation and volvulus 
syndrome, 547
for gastroenteritis, 555
for heat stroke/hyperthermia, 590
612–613
for infectious canine hepatitis, 
628–629
for infective endocarditis, 446
for infertility, 768
for influenza, 773–774
for intussusception, 789
for keratoconjunctivitis sicca, 800
perforation, 811for Lyme borreliosis, 848
for multidrug‐resistant infections, 910
for mycobacterial infections, 923
for mycoplasmosis, 925
for nasal discharge, 959
for neonates, 964, 966
for nephrolithiasis, 971
nephrotoxic, 974
for nocardiosis, 17, 980
for ophthalmia neonatorum, 994, 995
for osteomyelitis, 1010
for otitis, 1014, 1016
for periodontal disease, 1064
for plague, 1080
for pneumocystosis, 1084
for polycystic kidney disease, 1105
for polypoid cystitis, 1111
for prostatitis/prostatic abscess, 1130, 
1134
for pyelonephritis, 1161
for pyoderma, 1163, 1164
for Q fever, 1176
resistance, 909–910
for salmonellosis, 1218
sensitivity testing, 1483–1484
for septic arthritis, 119
for septic shock, 1246
for small intestinal dysbiosis, 1263
for sneezing, reverse sneezing, and 
gagging, 1269
for staphylococcal infections, 
1292–1293
for traumatic dentoalveolar injuries, 
1354
for ulcerative keratitis, 799
for urinary tract obstruction, 1369Anthelminthics ( cont’d )

Index  1579
for vaginitis, 1398
Anticholinergics
for atrioventricular block, 153
for ptyalism, 1147
for sick sinus syndrome, 1251
for sinus arrhythmia, 1255
for sinus bradycardia, 1257
Anticholinesterases, for myasthenia 
gravis, 921
Anticoagulant rodenticide toxicosis , 
1206–1207
for aortic thromboembolism, 109–110
for hypercoagulability, 677
for pulmonary thromboembolism, 
1152
Anticonvulsants. See Antiepileptic drugs
Antidepressant toxicosis , 102–105
SSRIs and SNRIs, 102–103
tricyclics, 104–105
Antidiarrheal medications, 22, 301
Antidiuretic hormone (ADH). See 
Vasopressin
Antidotes, 1449–1451
for acute kidney injury, 24
for anorexia, 95
for azotemia and uremia, 160
for bile duct obstruction, 176
for bile peritonitis, 177–178
for cardiac glycoside plant toxicosis, 
225
for diisocyanate glue exposure, 408
for gastroduodenal ulceration/erosion, 
553
for granulomatous hepatitis, 627
for hematemesis, 601
for infectious canine hepatitis, 629
for insoluble oxalate plant 
toxicosis, 775
for liver fluke infestations, 837
for marijuana toxicosis, 869
for otitis media and interna, 1016for pancreatitis, 1028, 1030
for vomiting, 28, 1427
Antiepileptic drugs (AEDs)
for brain tumors, 129, 195, 892
for feline hyperesthesia syndrome, 503
for feline ischemic encephalopathy, 513
for genetic epilepsy in dogs, 454–455
for seizures/status epilepticus, 1226, 
1228
for subarachnoid cysts, 1303
Antifibrinolytics
for coagulopathies, 287, 288
for hypovolemic shock, 1244
for pericardial disease, 1060
for thrombocytopathies, 1326
Antifibrotics, for liver disease, 280–281, 
624
Antifreeze poisoning, 474–475
Antifungal agents
for aspergillosis, 123, 125
for blastomycosis, 180–181
for candidiasis, 207
282–283
for cryptococcosis, 345
for deep cutaneous mycoses, 361
for dermatophytosis, 371
for feline upper respiratory infections, 
525
for Malassezia  dermatitis, 860
for nasal dermatoses, 957
for otitis externa and media, 1014
for pythiosis, 1173
for sporotrichosis, 1282
for urinary tract infections, 840
Antihistamines (H1‐receptor antagonists)
for conjunctivitis, 322
for pruritus, 1142
for vomiting, 28Antihypertensive drugs
for hypertensive retinopathy, 1196, 
1198
Antimicrobial resistance, multidrug, 
909–910
Antimicrobial susceptibility testing, 
1483–1484
Antimicrobials. See Antibiotics
for acute hepatic failure, 615–616
for bile peritonitis, 178
syndrome, 264
for cholecystitis and choledochitis, 
266
for chronic hepatitis, 624–625
for copper associated hepatopathy, 330
for ductal plate malformation, 418
for Heinz body anemia, 83
for hepatocutaneous syndrome, 635
for hepatotoxicity, 644
for lead toxicosis, 815
for vasculitis, 1402
Antipyretics, 527
Antithrombotic agents. See also  
Anticoagulants; Aspirin; 
for aortic thromboembolism, 109
for dilated cardiomyopathy, 230
for hypertrophic cardiomyopathy, 
236–237
for venous thromboprophylaxis, 1152
Antituberculous drugs, 923
Antitussives/cough suppressants
for influenza, 774
Antivenoms/antivenins
snake, 1265, 1266–1267, 1449
spider, 1274, 1275
Antivipmyn, 1267
Antiviral agents
for feline herpesvirus infection, 502, 
797, 799
for feline immunodeficiency virus 
infection, 507

1580  Index  
for feline leukemia virus infection, 515
for herpetic conjunctivitis, 320
Anuria , 991–992
in acute kidney injury, 23, 24
Anxiety , 494–497. See also  Fear
car ride, 220–222
in cats, 494–495
in dogs, 496–497
separation, 1231–1233
Anxiolytics
for separation anxiety syndrome,  
1233
1333–1334
for veterinary visits, 491
Anxitane. See L‐Theanine
Aortic arch
double, 1399
persistent right fourth, 1399
Aortic body tumors, 256, 1058
Aortic stenosis , 106–107
Aortic thromboembolism (ATE) , 
108–110
in hypercoagulability, 677
in hypertrophic cardiomyopathy, 108, 
235, 236–237
Apgar scoring, 967
Apical abscess , 1343–1344
Apixaban, 242
Aplastic anemia , 82
Apocrine gland adenocarcinoma, 38
Apomorphine
for antidepressant toxicosis, 105
for chocolate toxicosis, 260–261
for poisoning (intoxication), 1098
Apoquel. See Oclacitinib
Appetite stimulants, 95, 743, 1432
Apudoma , 111
Arachnoid diverticulum , 1302–1303
Arcanobacterium pyogenes,  980
L‐Arginine, for pulmonary 
hypertension, 705
Arisaema amurense,  775
Arrhythmogenic right ventricular 
cardiomyopathy , 226–228
in cats, 226
in dogs, 227–228
Arsenic toxicosis, 1450
Arterial blood collection, 1490–1491Arterial thromboembolism. See Aortic 
thromboembolism
Arteriovenous fistula (AVF) , 112
Arteriovenous malformations (AVM) , 
112–114
of liver, 113–114
Arteritis, proliferative, of nasal philtrum, 
372, 956, 1401
Arthritis , 115–119. See also  
Osteoarthritis; Polyarthritis
septic, 118–119
Arthrocentesis with synovial fluid 
analysis , 1479–1482
Ascariasis , 1212
Ascites , 120–121
in acquired portosystemic shunting, 
1115, 1116–1117
in arteriovenous malformation of liver, 
113–114
in chronic hepatitis, 624, 625
in cirrhosis and fibrosis of liver, 281
in congestive heart failure, 317
in ductal plate malformation, 417
in nephrotic syndrome, 972, 973
in portal hypertension, 702–703
in portosystemic vascular anomaly, 
1120
Ascorbic acid
avoidance in liver disease, 616
for Chediak‐Higashi syndrome, 255
for cyanosis, 353
for osteogenesis imperfecta, 901
L‐Asparaginase, for lymphoma, 857
Aspergillosis , 122–125
disseminated invasive, 122–123
nasal, 124–125, 959, 1199
pneumonia, 1090, 1091
sinoorbital, in cats, 122, 124
Aspiration pneumonia , 1085
in petroleum hydrocarbon toxicosis, 
1074, 1075
in regurgitation, 1186
Aspiration reflex (reverse sneezing) , 
1268–1269
Aspirin
for cardiomyopathy, 230, 236, 242
for hepatoportal microvascular 
dysplasia, 641
for hypertrophic osteodystrophy, 712for infective endocarditis, 446
for lymphangiectasia, 850
for pain management, 1467
for protein‐losing enteropathy, 1137
Aspirin toxicosis , 126
Asthma and bronchitis, in cats , 
127–128
Astrocytoma , 129
Asystole, ventricular , 1413–1414
Ataxia , 130–131
Atenolol
for aortic stenosis, 107
for atrial fibrillation, 138
for atrial premature complexes, 140
for atrioventricular valve disease, 
155, 157
for hypertension, 460
for hypertrophic cardiomyopathy, 236
for sinus tachycardia, 1259
for supraventricular tachycardia, 1308
for ventricular arrhythmias, 1410, 
1417
for Wolff–Parkinson–White 
syndrome, 1408
Atipamezole, 759, 1449
Ativan. See Lorazepam
Atlantic ivy, 1453
Atlantoaxial instability , 132–133
Atlantoaxial subluxation, congenital, 
313, 314
Atopic dermatitis , 134–135. See also  
Allergic dermatitis
Atopica. See Cyclosporine
Atopy, 78–79, 134–135
Atovaquone
for babesiosis, 161, 460
for cytauxzoonosis, 356
Atrial fibrillation , 136–138
in dilated cardiomyopathy, 233–234
in patent ductus arteriosus, 1050
Atrial flutter , 136–138
Atrial premature complexes , 139–140
Atrial septal defect , 141
Atrial standstill , 142–143
Atrial wall tear , 144
Atrioventricular block , 146–153
first degree, 148–149
second degree Mobitz type I, 
150–151
second degree Mobitz type II, 
152–153
third degree (complete), 146–147Antiviral agents ( cont’d )

Index  1581
Atrioventricular valve dysplasia , 
154–155
Atrioventricular valvular stenosis , 
156–158
Atropine, 1449
for anterior uveitis, 99, 101
for babesiosis, 162
for beta receptor antagonist toxicosis, 
171
225
for cardiogenic shock, 1242
for cardiopulmonary resuscitation, 
244, 1413
for chorioretinitis, 273
for corneal disorders, 335, 336, 338
for hyphema, 718
for hypopyon and lipid flare, 742
for idioventricular rhythm, 754
for imidazoline toxicosis, 759
for ivermectin toxicosis, 792
for mushroom toxicosis, 919
for proptosis, 1128
response test, 150, 153, 1251, 1253, 
1255
for sinus arrest/sinoatrial block, 1253
for toad venom toxicosis, 1340
Attention deficit (hyperactivity) 
disorder (ADD/ADHD) 
medication toxicosis ,  
72–73
Aural polyps, 955
Aurotrichia, 372
Aurum metallicum, for nasal 
aspergillosis, 125
Australian cattle dog
cystinuria, 1376
deafness, 357
dermatomyositis, 940
mast cell tumors, 874
myotonia, 945
ptyalism, 1146
Australian cobberdog, cone degeneration, 
310Australian kelpie, cerebellar 
degeneration, 130, 248, 689
Australian shepherd
cobalamin malabsorption, 87, 89, 290
epilepsy, 454
intervertebral disc disease, 784
ivermectin sensitivity, 257, 363, 792, 
1221
merle ocular dysgenesis, 310
movement disorder, 907
neutropenia, 978
Pelger‐Huët anomaly, 1053
retinal disease, 310, 1193, 1195, 1197
Australian silky terrier
hypermetria and dysmetria, 689
salivary mucocele, 1214
Autonomic toxicity mushroom 
poisoning, 916–919
Autumn crocus, 1452
Avocado soybean unsaponifiables, 1472
Axonal neuropathies (axonopathies), 1107
Azapirones. See also  Buspirone
for feline aggression, 49, 50, 55
Azathioprine
for chronic hepatitis, 624
for cirrhosis and fibrosis of liver, 280
for episcleritis, 458
for immune‐mediated anemia, 85
for immune‐mediated 
thrombocytopenia, 1330
for inflammatory/immune colitis, 
301–302
for keratitis, 797
for lupus erythematosus, 846
for meningoencephalomyelitis of 
unknown origin, 898
for myasthenia gravis, 921
for orbital myositis, 1002
for panniculitis/steatitis, 1033
for pemphigus, 386, 1056
for retinal detachment, 185
for sterile nodular/granulomatous 
dermatoses, 383
for uveodermatologic syndrome, 1390
for vasculitis, 1400
Azithromycin
for colitis and proctitis, 301for cryptosporidiosis, 294
Azotemia , 159–160
B
B‐complex vitamins
B‐lines, 1544, 1545
Babesiosis , 161–162
Baby oil, for sebaceous adenitis, 1224
Bacillary angiomatosis, 164
Bacitracin‐neomycin‐polymyxin B, for 
corneal sequestrum, 338
Back pain , 961–962
Baclofen toxicosis , 163
Bacteremia , 1235–1236
Bacterial culture and sensitivity , 
1483–1484
Bacterial (staphylococcal) folliculitis. 
See also  Pyoderma
alopecia, 67, 68
papules and/or nodules, 380
vesicles/pustules, 386
Bacteriuria, 838
BAL (dimercaprol), 1450
Balinese cat
lysosomal storage disease, 689, 859, 
1107
Baneberry, 1452
Barbiturates, 1449. See also  
Pentobarbital; Phenobarbital
toxicosis, 758
Barking, excessive, 476–477
Barotrauma, 26
Bartonellosis , 164
blepharitis, 182, 183
endocarditis, 445, 446
Basal cell tumor , 165, 378
Basenji
chronic gastritis, 550
Fanconi syndrome/glucosuria, 308, 
489, 570
immunoproliferative enteropathy, 762
persistent pupillary membranes, 310
protein‐losing enteropathy, 849, 1136

1582  Index  
Bases, strong, exposure to, 1462
Basic life support, 243–244
Basophilia, 831
Basset hound
antebrachial growth deformities, 96
cervical spondylomyelopathy, 252
cyclic hematopoiesis, 354, 978
epistaxis, 459
histiocytic diseases, 650
hypotrichosis, 67
immunodeficiency disorder, 760
Malassezia  dermatitis, 860
pododermatitis, 1096
skin tumors, 378, 578
temporomandibular joint disorders, 
1318
thrombocytopathia, 1327
BAT (gator) sign, 1543, 1544
Battery toxicosis , 166
Baylisascariasis , 167
Baylisascaris,  167, 1212
Baytril. See Enrofloxacin
BCAN  gene, 907
Beagle
amyloidosis, 74, 308
brucellosis, 202
cerebellar disease, 130, 247, 248, 689
chorioretinitis, 272
cleft palate, 1025
cyanosis, 352
diabetes mellitus, 399
facial nerve paralysis, 483
gallbladder mucocele, 265
hemotropic mycoplasmosis, 607
hyperadrenocorticism, 668
immunodeficiency, 760
infertility, 769
intervertebral disc disease, 130, 781, 
1040
juvenile polyarteritis, 74, 1401
kidney disease, 308, 1105, 1138
Lyme borreliosis, 847lysosomal storage disease, 859
neck and back pain, 961
obesity, 986
osteochondrodysplasia, 1006
osteogenesis imperfecta, 900
polyphagia, 1109
pulmonic stenosis, 1153
right bundle branch block, 1202
skin tumors, 378, 1289
small intestinal dysbiosis, 1262
steroid‐responsive meningitis‐arteritis, 
894, 1294
systemic lupus erythematosus, 845
thyroid adenocarcinoma, 40
ventriculomegaly, 663
Bearded collie
elbow dysplasia, 438
hypoadrenocorticism, 719
thrombocytopenia, 1329
vesiculopustular dermatoses, 385
Beauceron shepherd
dermatomyositis, 367
digital squamous cell carcinoma,  
1283
Bedlington terrier
acute hepatic failure, 614
copper associated hepatopathy, 279, 
328–331, 622
epiphora, 456
icterus, 752
mibolerone contraindication, 
768, 878
portal hypertension, 701
retinal dysplasia, 1193, 1195, 1197
BEG (boutique, exotic‐ingredient, 
grain‐free) dog foods, 239, 240
Behavior therapy
for canine aggression, 42–43, 44–45, 
47–48, 51–52
for car ride anxiety, 220
for compulsive disorders, 307
for destructive behavior, 389–390
for excessive vocalization, 476–477
494, 496
for feline aggression, 49, 54
for housesoiling, 658–659, 661–662for separation anxiety syndrome, 1232
1333
Belgian Malinois
cerebellar degeneration, 247
ehrlichiosis, 436
lumbosacral stenosis, 841
Belgian shepherd
gastric carcinoma, 39
gastroduodenal ulceration/erosion, 
552
mucopolysaccharidosis, 908
Belgian Tervuren
Belladonna lily, 1452
Benazepril
for cardiomyopathy, 230, 233, 236
for congestive heart failure, 316, 318
for hypoalbuminemia, 723
for myxomatous mitral valve 
disease, 952
Bengal cat
pectus excavatum, 1052
polyneuropathy, 1107
Benign prostatic hyperplasia 
(BPH) , 168
in breeding male dog, 1129, 1130
prostatomegaly, 1134
Benzimidazole, for Chagas disease, 254
Benzodiazepine toxicosis , 169–170
for antidepressant toxicosis, 102, 103
for beta‐2 agonist inhaler 
toxicosis, 172
for black widow spider envenomation, 
1274
for canine aggression, 43, 45, 48, 60
495, 497

Index  1583
1334
for urinary retention, 1366
Benzopyrones, for lymphedema, 853, 
1066
Benzoyl peroxide
for acne, 14, 380
Bernard Soulier syndrome, 1327
Bernese mountain dog
anemia, 90
cerebellar degeneration, 130, 247
degenerative myelopathy, 209
episcleritis, 458
granulomatous sebaceous adenitis, 
1224
histiocytic diseases, 650, 652
hypomyelination, 733
kidney disease, 308, 566, 1138
Lyme borreliosis, 847
osteochondrosis, 1007
pyometra, 1165
sterile nodular/granulomatous 
dermatoses, 382
894, 1294
Bernese running dog, cerebellar 
degeneration, 247, 689
Beta‐2 agonist inhaler toxicosis , 172
Beta‐2 agonists
for smoke inhalation, 1264
Beta blocker toxicosis , 171
Beta blockers ( β‐adrenergic blockers)
for atrial fibrillation, 137, 138for atrioventricular valve disease, 
155, 157
for beta‐2 agonist inhaler toxicosis, 
172
for dilated cardiomyopathy, 230, 233
for glaucoma, 565
236, 238
for myocardial infarction, 933
for systolic anterior motion, 1316
for tetralogy of Fallot, 1322
for thyroid adenocarcinoma, 41
1417
Beta receptor antagonist toxicosis , 171
Betamethasone, for pemphigus, 1056
Betaxolol, for glaucoma, 565
Bethanechol
for dysautonomia, 419, 1108
for intervertebral disc disease, 786
for urinary retention, 1366, 1367
Bezafibrate, 686
Bicarbonate (HCO3−)
arterial blood, 1485–1487
therapy. See Sodium bicarbonate
Biceps brachii tendon, ruptured origin 
of, 1247, 1248, 1249
Bichon frisé
epileptoid cramping syndrome, 946
gallbladder mucocele, 544
hepatoportal microvascular dysplasia, 
639, 640
immune‐mediated anemia, 84
patent ductus arteriosus, 1049
urolithiasis/crystalluria, 348, 970, 
1372
Bicipital tenosynovitis, 1247, 1248, 
1249
“Big kidney, little kidney syndrome,” 
1363
Bile duct carcinoma , 173
Bile duct malformation. See Ductal plate 
malformation
Bile duct obstruction  (extrahepatic) 
(EHBDO) , 174–176
cholangitis/cholangiohepatitis 
syndrome, 262
cholecystitis and choledochitis, 265
cholelithiasis, 267
Bile peritonitis , 177–178
Biliary‐enteric anastomosis, 175Bilious vomiting syndrome , 179
Bilirubin crystalluria, 348, 349
Bimatoprost, for glaucoma, 565
Biochemical tests
reference ranges, 1441–1442
unit conversion table, 1443
Birman cat
behavioral problems, 304, 388
blood type, 1499
cryptococcosis, 360
nystagmus, 984
Birt‐Hogg‐Dube syndrome, 1387
Bisacodyl, 324
Bismuth subsalicylate (Pepto‐Bismol), 
537, 592
Bisphosphonates
for anal sac adenocarcinoma, 29
for chondrosarcoma, 269, 271
for fibrosarcoma, 532
for hypercalcemia, 673
Bitter orange, 1459
Bittersweet, 1452
Black hair follicular dysplasia, 67
Black Russian terrier, hyperuricuria, 308
Black urine, diagnostic algorithm, 603
Black widow spider venom toxicosis , 
1274
Bladder, urinary
pelvic, 1054
transitional cell carcinoma, 431, 
1350–1351
urethral catheterization, 1559–1562
vesicourachal diverticula, 1421
Blastomycosis , 180–181
chronic rhinitis, 1199
deep cutaneous, 360–361
Bleaches, exposure to, 1462
Bleeding heart (plant), 1452
Blepharitis , 182–183
Blepharospasm, 1325
Blind quiet eye , 184–185
Blood banks, 1571
Blood cultures, 1483
Blood gas interpretation , 1485–1487
Blood pressure (BP), 706, 707
Blood pressure determination: 
noninvasive and invasive , 
1488–1489
Blood sample collection , 1490–1491
Blood smears , 1492–1497
microscopic examination, 1492–1495
preparation, 1496–1497

1584  Index  
Blood transfusion. See T ransfusion 
therapy
Blood transfusion reactions , 186
Blood typing , 1498–1500
Bloodhound
ectropion, 435
keratoconjunctivitis sicca, 800
Blue flag (iris), 1454
Blue‐green algae toxicosis , 187
Blue‐tailed lizard ingestion, 1424
Bluebonnet ( Lupinus  spp.), 1454
Bluetick hound, lysosomal storage 
disease, 859
Bobtail dog, histiocytoma, 650
Body condition score (BCS), 986, 1431
Body surface area, 1569
Boerboel, spinal dysraphism, 1276
Bone disorders, metabolic, nutritional, 
and endocrine , 900–901
Bone marrow aspirates , 1501–1506
and biopsy, 1501–1502
cytology: microscopic evaluation, 
1503–1506
Bone tumors
chondrosarcoma, 269
fibrosarcoma, 532
hemangiosarcoma, 594
osteosarcoma, 1011–1012
Border collie
cerebellar degeneration, 130, 689
cobalamin malabsorption, 87, 
290, 978
compulsive disorders, 306
cutaneous histiocytosis, 650
histiocytic ulcerative colitis, 300, 303
pyothorax, 1168
sensory neuropathy, 1107
Border terrier
dystocia, 428
epileptoid cramping syndrome, 
907, 946
glucosuria, 570
renal disorders, 308
Bordetella bronchiseptica,  215, 216, 524
Bordetellosis, 215Borrelia burgdorferi,  847–848
‐associated glomerulonephritis, 566
tick vectors, 1338–1339
vaccines, 848
Borzoi
chorioretinopathy, 272
spontaneous abortion, 4
Bosentan, 705
Boston terrier
brachycephalic airway syndrome, 
190, 1295
cerebellar hypoplasia, 248
chemodectoma, 256
craniomandibular osteopathy, 341
glycogen‐type vacuolar 
hepatopathy, 574
hydrocephalus, 663
hypertrophic cardiomyopathy, 238
hypertrophic pyloric gastropathy, 714
papillomatosis, 1039
patellar luxation, 1047
pericardial disease, 1058
regurgitation, 1185
retinal detachment, 1195
skin tumors, 378, 888
status epilepticus, 1227
syringomyelia and Chiari‐like 
malformation, 1312
ulcerative keratitis, 798
urethral prolapse, 1365
vascular ring anomalies, 1399
vertebral malformations, 313
Botulinum type C antitoxin, 188
Botulism , 188
Boutique, exotic‐ingredient, grain‐free 
(BEG) dog foods, 239, 240
Bouvier des Flandres
aortic stenosis, 106
dysphagia, 422
exercise‐induced weakness/collapse, 
478
laryngeal paralysis/polyneuropathy, 
812, 1107, 1295
lymphoma, 851ovulatory failure, 1020
ulcerative stomatitis, 1297
Bovine lactoferrin, 519
Bowen’s‐like disease/Bowenoid 
carcinoma in situ. See  
Multicentric squamous cell 
carcinoma in situ
Boxer
acne, 15
acral lick dermatitis, 16
antibiotic‐responsive diarrhea, 402
arrhythmogenic right ventricular 
cardiomyopathy, 227–228, 1415
atrial septal defect, 141
brain tumors, 194, 891
carnitine deficiency, 239, 240
chondrosarcoma, 269, 270, 271
coccidioidomycosis, 360
colibacillosis, 298
congestive heart failure, 317
dentigerous cyst, 366
diarrhea, 405
239, 240
ductal plate malformation/congenital 
hepatic fibrosis, 279, 416
eosinophilic gastroenteritis, 556
gingival enlargement/hyperplasia, 563
granulomatous colitis, 300, 303
head tremors, 585, 1355
hemangiosarcoma, 596
hypertrophic osteodystrophy, 711
infertility, 767
inflammatory bowel disease, 771
insulinoma, 776
mammary gland tumors, 867
neuroaxonal dystrophy, 977
odontogenic tumors, 988
ovarian tumors, 1019

Index  1585
plasmacytoma, 1081
polymyositis, 940
protothecosis, 442, 1141
renal dysplasia, 308
sick sinus syndrome, 1250, 1256
sinus arrest/sinoatrial block, 1252
sinus arrhythmia, 1254
spinal dysraphism, 1276
splenomegaly, 1279
894, 1294
syncope, 1309
1393, 1394
vaginal tumors, 1396
ventricular arrhythmias, 1409, 1410, 
1415, 1416, 1417
Boxer cardiomyopathy, 227–228
Boykin spaniel, exercise‐induced 
weakness, 478
Brachial plexus avulsion , 189
Brachycephalic airway syndrome 
(BAS) , 190–191
laryngeal collapse, 812
panting and tachypnea, 1036
Brachycephalic obstructive CSF channel 
syndrome. See Chiari‐like 
Bradycardia–tachycardia syndrome,  
1251
Brain injury , 192–193
Brain tumors , 194–195. See also  
Astrocytoma; Meningioma
Breeding, timing , 196–197
Breeding soundness examination, male 
dogs, 770
Briard
digital squamous cell carcinoma, 1283
hyperlipidemia, 685
retinal dystrophy, 310, 1193
Brimonidine toxicosis, 759
Brinzolamide, 565, 718, 1388
British Blue cat
basal cell tumor, 165
polycystic kidney disease, 308British shorthair cat
polycystic kidney disease, 1105
Brittany spaniel
cerebellar degeneration, 130, 247, 689
kidney disease, 308, 1138
spinal muscular atrophy, 1107
Brodifacoum toxicosis, 1206
Bromadiolone toxicosis, 1206
Bromethalin rodenticide toxicosis , 
1208
Bromocriptine
for false pregnancy, 486
Bronchiectasis , 198–199
Bronchiolitis obliterans with organizing 
pneumonia (BOOP), 1092, 
1093
Bronchitis, chronic , 200–201
feline, 127–128
for interstitial pneumonia, 1093
Bronchomalacia, 1348
Brown recluse spider venom toxicosis , 
1275
Brucella canis,  4, 5, 202, 1398
Brucellosis , 202–203
discospondylitis, 412
epididymitis and orchitis, 453
spontaneous abortion, 5
Brugmansia  spp., 1453
Bruising , 1072–1073
Brussels griffon, Chiari‐like 
Buccal mucositis, 1297
Budesonide
for chronic gastritis, 551for cough, 340
for inflammatory bowel disease, 557, 
772
Bull terrier. See also  English bull terrier
cutaneous histiocytosis, 652
kidney disease, 274, 308, 1138, 1188
laryngeal paralysis, 812, 1295
mitral valve disease, 154, 156
neoplastic dermatoses, 378
Bulldog. See also  American bulldog; 
English bulldog; French bulldog
edema/lymphedema, 853, 1065
lymphoma, 856
otitis externa and media, 1013
quadrigeminal cyst, 1177
spina bifida, 313
Bullmastiff
lymphoma, 851
pregnancy edema, 1123
Bullous pemphigoid, 385, 386
Bupivacaine, 429, 1022, 1466
Buprenorphine
for pain management, 1022, 1465
for urolithiasis, 1380

1586  Index  
Burmese cat
blepharitis, 182
corneal sequestrum, 798
crystalluria, 348
diabetes mellitus, 397
dilated cardiomyopathy, 229
hypokalemic periodic paralysis, 729
stomatitis, 519
urolithiasis, 1372
Burns, 65
in electric cord injury, 440
solar‐induced thermal, 384
Buserelin, for cryptorchidism, 346
Buspirone
495, 497
for feline aggression, 49, 55, 57
Busulfan, for polycythemia vera, 463
Butorphanol
for electric cord injury, 440
for pain management, 1465
for pancreatitis, 1028
C
Cabergoline
for hypersomatotropism in cats, 700
for pyometra, 1166for spontaneous abortion, 3
Cachexia , 1431–1433
Caffeine toxicosis, 260–261, 1458
Cairn terrier
hemophilia B, 286‐287
hepatoportal microvascular 
dysplasia, 639
kidney disease, 274, 308, 1105, 1188
Legg–Calvé–Perthes disease, 820
portosystemic vascular anomaly, 1118
pseudomacrothrombocytopenia, 1145
Calcinosis circumscripta, 382, 383
Calcinosis cutis, 382, 383
Calcipotriene/calcipotriol 
toxicosis , 204
Calcitonin salmon, 1210, 1449
Calcitriol, 696, 737
Calcium acetate, 696, 737
Calcium carbonate
for eclampsia, 433
for hypoparathyroidism, 737
Calcium channel blocker toxicosis , 205
Calcium channel blockers
for atrial fibrillation, 137–138
for atrioventricular valve 
dysplasia, 155
236, 238
Calcium chloride, 205, 725, 1449
Calcium citrate, 737
Calcium disodium EDTA (CaEDTA), 
815, 1437, 1449
Calcium glubionate, 737
Calcium gluconate, 1449
toxicosis, 171for blood transfusion reactions, 186
for hyperkalemia, 24, 683
for hypermagnesemia, 688
for hypocalcemia, 41, 429, 725
for retained placenta, 1192
for uterine inertia, 1386
Calcium lactate, 737
Calcium oxalate crystalluria, 348, 349
Calcium oxalate urolithiasis , 
1372–1374
nephrolithiasis, 970, 971
ureterolithiasis, 1363
Calcium phosphate crystalluria, 348, 349
Calcium phosphate urolithiasis , 1375
Calcium supplements
for hypocalcemia, 725
CalDAG‐GEFI thrombocytopathia, 
1327
Calming Care probiotic, 1158
Campylobacteriosis , 206
Canarc‐1  gene, 954
Candelabra plant, 1452
Candida  spp., 207, 840
Candidatus Mycoplasma haemominutum,  
607
Candidiasis , 207
Cane (marine) toad intoxication, 1340
Canine acanthomatous ameloblastoma 
(CAA), 988, 989
Canine adenovirus‐1 (CAV‐1), 628–629
Canine adenovirus‐2 (CAV‐2), 215, 216
Canine coronavirus infections , 208
feline infectious peritonitis, 512
Canine degenerative myelopathy , 
209–210
Canine distemper , 211–212
Canine distemper virus (CDV), 211
erosive polyarthritis, 1101
myoclonus, 937
vaccines, 212, 216
Canine enteric coronavirus (CCoV), 208
Canine epileptoid cramping syndrome, 
907, 946
Canine herpesvirus conjunctivitis, 322
Canine herpesvirus infection , 964–965
Canine infectious diarrhea , 213–214
Canine infectious respiratory disease , 
215–216
Canine influenza viruses (CIV), 215, 
216, 773–774

Index  1587
Canine leproid granuloma, 922, 923
Canine monocytic ehrlichiosis (CME), 
436, 437
Canine pantropic coronavirus 
(CPCoV), 208
Canine papillomavirus (COPV), 1039
Canine parainfluenza virus (CPIV), 
215, 216
Canine parvovirus (CPV‐2) , 217–218
diarrhea, 213
feline panleukopenia, 516
vaccines, 218
Canine respiratory coronavirus 
(CRCoV), 208, 215
Canine schistosomiasis , 219
Cannabidiol (CBD), 1023
Cannabis (marijuana) toxicosis , 869
Capillaria (Eucoleus) aerophilus,   
Capillaria (Eucoleus) boehmi,  1190–1191, 
1523
Capillaria (Pearsonema) feliscati,  1370, 
1371
Capillaria (Pearsonema) plica,  1370, 
1371
Capromorelin
for hyporexia, 743
for weight loss and cachexia, 1432
Car ride anxiety , 220–222
Carbamate toxicosis , 1003–1004
Carbimazole, for hyperthyroidism, 710
Carbofuran toxicosis, 1003
Carbon dioxide, partial pressure in blood 
(PCO2), 1485–1487
Carbon monoxide toxicosis , 223
Carbonic anhydrase inhibitors
for lens luxation, 827
for uveal melanoma, 1388
Carboplatin
for adenocarcinoma, 29, 30, 31, 41
for carcinoid tumors, 224
for melanocytic tumors, 887
for mesothelioma, 899
neutropenia after, 979
for squamous cell carcinoma, 1285, 
1286, 1287, 1289, 1290, 1291
for transitional cell carcinoma, 1351
for vaginal tumors, 1396
Carcinoid and carcinoid syndrome , 
224
Cardiac glycoside plant toxicosis , 225
Cardiac tamponade, 1058Cardiac tumors
hemangiosarcoma, 595
myocardial, 934
pericardial disease, 1058, 1059, 1060
Cardigan Welsh corgi. See also  Welsh corgi
rod cone dysplasia, 310
Cardiogenic shock , 1241–1242
Cardiomyopathy , 226–242
arrhythmogenic right ventricular, 
226–228
dilated. See Dilated cardiomyopathy
hypertrophic. See Hypertrophic 
cardiomyopathy
nutritional, 239–240
restrictive, in cats, 241–242
Cardiopulmonary arrest , 243–244
Cardiopulmonary resuscitation (CPR), 
243–244, 415, 1405–1406, 
1413–1414
Cardioversion, electrical, 136–137
Caries, dental , 364–365
Carminatives, 537
Carnitine (L‐carnitine)
for cardiomyopathy, 227, 233, 240
deficiency, 239–240
for hepatic encephalopathy, 613
for hepatic lipidosis, 618
insufficiency, 239
for myopathies, 942, 944, 949
Caroli’s malformation, 416, 417
Carotid body tumors, 256
Carprofen
for anterior uveitis, 101
for elbow dysplasia, 439
for hip dysplasia, 648
for hypopyon, 742
for joint luxations, 794
for Legg–Calvé–Perthes disease, 821
for lumbosacral stenosis, 842
for neuropathic pain, 1276
for osteoarthritis, 116, 1470, 1471
for pain management, 1466, 1467
for panosteitis, 1035
for patellar luxation, 1048
for red eye, 1183
toxicosis, 981
for vertebral column trauma, 1420Carvedilol, 107, 233, 316
Casozepine. See Alpha‐casozepine
Caspofungin, 123, 1084
Castor bean, 1452
Castration (orchiectomy)
for alopecia, 70
for benign prostatic hyperplasia, 168
for canine aggression, 43, 45
for feline aggression, 54
for hyperestrogenism, 680
for perineal hernia, 1061
for prostatic disease, 1130, 1133
for testicular tumors, 779, 1230, 1237
for urethral prolapse, 1365
Cat carriers, for veterinary visits, 491
Cat scratch disease, 164
Catahoula leopard dog, 
Cataplexy , 954
Cataracts , 245–246
blind quiet eye, 184
congenital, 245, 310, 311
Cathartics
Cathedral bells, 1452
Cationic detergents, 1460
Cauda equina syndrome , 841–842
Caudal mucositis, feline, 519, 1297
Caudal occipital malformation 
Cavalier King Charles spaniel
anal sac adenocarcinoma, 29
brachycephalic airway syndrome, 190
cerebrovascular accident, 249
Chiari‐like malformation, 130, 1276, 
1312, 1313, 1314
cobalamin deficiency, 290
diaphragmatic hernia, 401
dry eye and curly coat syndrome, 310
eosinophilic granuloma, 451
episodic falling syndrome, 907, 946
keratitis, 796
masticatory muscle myositis, 938
myxomatous mitral valve disease, 951

1588  Index  
otitis media, 1013, 1015
pancreatitis, 1029
paralysis, 1040
pneumocystosis, 1084
pseudomacrothrombocytopenia, 1145, 
1329
syringomyelia, 1312, 1313, 1314
xanthinuria, 308, 348, 1385
CCNU. See Lomustine
Cefadroxil, 1293
Cefazolin
Cefotaxime
Cefovecin
for otitis media and interna, 1016
Cefoxitin, 76, 299, 547
Cefpodoxime, 1016
Ceftiofur, 966
Celastrus  spp., 1452
Cellulitis
canine juvenile (puppy strangles), 
1159
Central nervous system (CNS) bacterial 
infections, 894–895
Centronuclear myopathy of Labrador 
retrievers, hereditary, 943
Cephalexin
for otitis, 1014
Cephalosporins
for infective endocarditis, 446for mastitis, 876
for peritonitis, 1071
Cephalothin, 527
Cephradine, 412
Cerebellar abiotrophy, 130, 247, 248
Cerebellar degeneration , 247
Cerebellar disease, 130, 247–248, 689
Cerebellar hypoplasia , 248
Cerebral edema
in brain injury, 192
in brain tumors, 194
in bromethalin rodenticide toxicosis, 
1208
in cerebrovascular accidents, 246
in diabetic hyperosmolar 
hyperglycemic state, 394
in heat stroke/hyperthermia, 590
in hepatic encephalopathy, 611, 
613, 615
in seizures, 1127, 1225
Cerebrovascular accidents (CVA) , 
249–250
Cerenia. See Maropitant
Ceruminolytics, 1014
Ceruminous gland adenocarcinoma, 
ear, 251
Cervical intervertebral disc disease , 
781–783
Cervical sialocele, 1214, 1215
Cervical spondylomyelopathy , 
252–253
ataxia, 130
neck pain, 961
Cesarean section, 429
Cestodiasis , 1317
Cetirizine, 135, 521
Chagas disease , 254
Chalazia, 182
Chamomile, 1457
Charcoal, activated. See Activated 
charcoal
Chasing behavior, dogs , 1361–1362
Chediak‐Higashi syndrome , 255
depigmentation, 372, 373
Cheilitis, 1297
Chelation therapy
for zinc toxicosis, 1437
Chemodectoma , 256
pericardial disease, 1058, 1060
for ameloblastoma, 71
for anal sac adenocarcinoma, 29–30for brain tumors, 129, 195, 892
for chondrosarcoma, 269
for chronic lymphocytic leukemia, 
830
5‐fluorouracil (5‐FU) toxicosis, 1
for gastrointestinal adenocarcinoma, 
39
for glucagonoma, 568
for hemangiopericytoma, 593
for hemangiosarcoma, 594, 595, 596, 
598–599
for hypereosinophilic syndrome, 678
for lymphoma, 855, 857, 858
for malignant fibrous histiocytoma, 
861
for mammary gland tumors, 866, 868
for mast cell tumors, 875
for melanocytic tumors, 887, 888
for meningioma, 892
for multiple myeloma, 911
for myelodysplastic syndromes, 928
for myeloproliferative disorders, 932
for nasal carcinoma, 33
nephrotoxic drugs, 974
for nerve sheath tumors, 976, 1223
for oral cavity undifferentiated 
malignant tumors, 1000
for ovarian tumors, 1019
for pancreatic adenocarcinoma, 34
for plasmacytoma, 1081
for prostatic adenocarcinoma, 35
for pulmonary adenocarcinoma, 31
for salivary gland adenocarcinoma, 37
for skin tumors, 38, 1289
for soft tissue sarcoma, 1271
for synovial cell sarcoma, 1311
for transmissible venereal tumor,  
1352
for uterine tumors, 1387
Cherry eye , 1127
Chesapeake Bay retriever
478
1393, 1394
von Willebrand disease, 459, 1072, 
1429Cavalier King Charles spaniel ( cont’d )

Index  1589
Chest tube placement
for actinomycosis and Nocardia,  17
for chylothorax, 278
for pleural effusions, 1082–1083
for pneumothorax, 1095
for pyothorax, 1168–1169
Cheyletiellosis , 257
Chiari‐like malformation , 1312–1314
Chihuahua
atlantoaxial instability, 132, 961
cystine urolithiasis, 1376
eclampsia, 433
iris atrophy, 790
necrotizing encephalitis, 442, 963
pinnal alopecia, 67, 68
tracheal collapse, 1348
Children, aggression of dogs 
toward , 46
Chinaberry tree, 1453
Chinese crested
alopecia, 67
lens luxation, 827
missing teeth, 1341
Chinese shar‐pei. See Shar‐pei
Chinook, movement disorder, 907
Chiropractic therapy, 786
Chlamydiosis, feline , 258–259, 320
Chlorambucil
830
for immune‐mediated anemia, 85for immune‐mediated 
for inflammatory bowel disease, 404
301, 302
for lymphoma, 855, 857
for polyarthritis, 1104
for polycythemia vera, 463
Chloramphenicol
for conjunctivitis, 320
for Rocky Mountain spotted fever, 
1205
Chlorhexidine
for acne, 15, 380
for exfoliative dermatoses, 377
for otitis externa, 1014
1354
Chloride‐resistant metabolic alkalosis, 
63, 64
Chloride‐responsive metabolic alkalosis, 
63, 64
Chlorophacinone toxicosis, 1206
Chlorpheniramine, 16, 135, 521
Chlorpromazine
Chlorpyrifos toxicosis, 1003, 1004
Chlortetracycline, 203
Chocolate toxicosis , 260–261
Cholangiocarcinoma, 173
Cholangitis/cholangiohepatitis 
syndrome (CCHS) , 262–264
Cholecalciferol rodenticide toxicosis , 
1209–1210
Cholecystitis and choledochitis , 
265–266
Choledochal cyst, 416, 417
Cholelithiasis , 267–268
Cholesterol crystals, urinary, 349
Cholestyramine, 204, 616Chondroitin sulfate
for osteoarthritis, 116, 1472
toxicosis, 1458
Chondroprotective agents
for cranial cruciate ligament 
disease, 343
for lameness, 809
Chondrosarcoma , 269–271
bone, 269
nasal and paranasal sinus, 270
oral, 271
CHOP/COP‐based chemotherapy, 
855, 857
Chorionic gonadotropin. See Human 
chorionic gonadotropin
Chorioretinitis , 272–273
Choroiditis, 98, 100
Chow chow
cerebellar disease, 130, 248, 689
color dilution alopecia, 67, 376
entropion, 182, 449, 482
gastroduodenal ulceration/erosion, 552
hiatal hernia, 646
hypomyelination, 733, 1355
melanocytic tumors, 886, 888
uveodermatologic syndrome, 272, 1390
Christmas rose, 1453
Chronic bronchitis. See Bronchitis, 
chronic
Chronic hepatitis , 622–625
Chronic kidney disease (CKD) , 
274–276
acute kidney injury, 23
anemia of, 80–81, 87, 88
congenital and developmental, 
308–309
perirenal pseudocysts, 1067
secondary hyperparathyroidism, 
696–697

1590  Index  
Chronic lymphocytic leukemia , 830
Chronic myelogenous leukemia, 932
Chronic pain , 1021–1024
Chronic ulcerative paradental stomatitis, 
1297
Chyloabdomen, 1477
Chylothorax , 277–278
Chylous effusion, 1527, 1528, 1529
Cidofovir
for feline herpesvirus infection, 502, 797
for herpetic conjunctivitis, 320, 322
Cilia, ectopic , 482
Ciliary dyskinesia, primary (PCD), 198, 
769, 1273
Cimetidine
for methemoglobinemia, 353
Cinnamon, 1458
Cinnamon oil, 472, 1457
Ciprofloxacin, 320, 335, 839
Cirrhosis of the liver , 279–281
Cisapride
for bilious vomiting syndrome, 179
for brachycephalic airway 
syndrome, 191
for brain injury, 193
for constipation, 324
for esophageal foreign bodies, 465
for esophagitis, 468, 470, 471
for gastric motility disorders, 549
for gastroesophageal reflux, 558
for hiatal hernia, 646
for ileus, 757
for megacolon, 882
for megaesophagus, 884
for regurgitation, 1186
for stupor and coma, 1301
Cisplatin
for adenocarcinoma, 29, 31, 33
1286, 1287, 1291
for vaginal tumors, 1396Citrus oil, 1457
Clarithromycin, 592, 923
Clavamox. See Amoxicillin‐clavulanic acid
Clavaseptin. See Amoxicillin‐clavulanic 
acid
Claw and clawfold disorders , 282–283
Claw dystrophy, 282
Cleaning agents, toxic, 1460–1461
Cleft palate, 424, 1025–1026
Climbazole, 371
Clindamycin
for acne, 14
584, 895
for hepatozoonosis, 645
for neosporosis, 969
for toxoplasmosis, 1191, 1347
Clomipramine
for canine aggression, 43, 45, 46, 48, 60
495, 497
for feline aggression, 49–50, 54, 57
for housesoiling, 659, 662
behavior, 871, 873
for polyphagia, 1110
for separation anxiety syndrome, 
1232–1233
for thunderstorm and noise 
phobias, 1334Clonazepam
for episodic falling syndrome, 946
phobias, 1334
Clonidine
1334
Clonorchis conjunctus,  836
Clonorchis sinensis,  836
for heartworm disease, 588
Cloprostenol, 5, 6, 7, 1166
Clorazepate, 455, 497, 937
Clostridial enterotoxicosis , 284–285
Clostridium botulinum,  188
Clostridium difficile,  301
Clostridium perfringens,  284, 301, 
554, 555
Clostridium tetani,  1320
Clotrimazole, 125, 460, 840
Clove oil, 472
Club drug toxicosis , 758
Clumber spaniel, metabolic 
myopathy, 946
Coagulation factor deficiency , 
286–287
anemia in, 90, 91
in bile duct obstruction, 174
epistaxis in, 459, 460
hematemesis in, 600
hemothorax in, 606
Coagulopathy of liver disease , 288–289
Cobalamin deficiency , 290–291
anemia, 87, 89
in exocrine pancreatic insufficiency, 
480, 481

Index  1591
Cobalamin (vitamin B12). See also  
Hydroxycobalamin
for cobalamin deficiency, 88, 89, 290
congenital malabsorption, 87, 89, 978
for inflammatory bowel disease, 772
Cocaine toxicosis, 758
Coccidioidomycosis , 292–293
Coccidiosis , 294
Cochlear degeneration, 357
Cocker spaniel. See also  American cocker 
spaniel; English cocker spaniel
anemia, 84, 1548
atrioventricular block, 146
bronchiectasis, 198, 200
cheyletiellosis, 257
claw and clawfold disorders, 282
cryptococcosis, 360, 1090
cyclic hematopoiesis, 354
dilated cardiomyopathy, 232
ear canal tumors, 251, 1284
478
fiber‐responsive large bowel 
diarrhea, 528
hepatic disease, 279, 622, 752
hepatotoxin susceptibility, 643
784, 1040
otitis media and interna, 1015pancreatitis, 1029
pemphigus foliaceus, 372, 1055
polyarthritis, 1101, 1103
retinal dysplasia, 1193
skin tumors, 165, 378, 578
superficial necrolytic dermatitis, 1306
thrombocytopenia, 1072, 1331
Codeine
for osteoarthritis, 116
toxicosis, 996–997
Coenzyme Q10, 240, 316, 949
Cognitive dysfunction syndrome 
(CDS) , 295–296, 476
Cohosh, 1452
Colace. See Docusate sodium/calcium
Colchicine
for amyloidosis, 75, 610
for superficial necrolytic dermatitis, 
1306
Colchicum autumnale,  1452
Cold agglutinin disease , 297
Colibacillosis , 298–299
Colic. See Acute abdomen
Colitis , 300–302. See also  Diarrhea
granulomatous, 300, 301, 303
histiocytic ulcerative, 303
infectious, 300, 301, 302
inflammatory/immune, 301
Collagenous nevi, 382, 383
Collapse, exercise‐induced, in 
Labrador retrievers , 478–479
Collie. See also  Bearded collie; Border 
collie; Gray collie; Rough‐coated 
collie
amyloidosis, 74, 609
cyclic hematopoiesis, 354, 372, 373
dermatomyositis, 367, 374, 385, 956
histiocytic diseases, 650immune‐mediated anemia, 84
ivermectin sensitivity, 257, 363, 792
lupus erythematosus, 372, 385, 844, 
845, 956
nodular episclerokeratitis. See Collie 
granuloma
opiate/opioid toxicosis, 996
polyarthritis, 1101
rectoanal polyps, 1182
vasculitis, 1400, 1401
Collie eye anomaly (CEA), 310
hyphema, 717
retinal disease, 1195, 1197
Collie granuloma (nodular 
granulomatous episclerokeratitis; 
NGE), 182, 458, 796
Colobomas, 310, 311
Color dilution alopecia, 67, 376
Colorado River toad intoxication, 1340
Colorectal polyps, 300
Coma , 1300–1301
COMMD1  mutation, 328, 329, 331
Complete ophthalmologic exam , 
1507–1511
Compulsive disorders , 304–307
in cats, 304–305
destructive and scratching behavior, 388
in dogs, 306–307
feline psychogenic alopecia, 66, 
304–305
Concerta. See Methylphenidate
Cone degeneration, 310, 311, 1193
Cone rod dystrophy, 310
Confinement training, for puppies, 
1155–1156
Conflict aggression, in dogs, 58
Congenital adrenal hyperplasia, 1238
Congenital and developmental renal 
diseases , 308–309
Congenital hepatic fibrosis (CHF) , 
416–418
Congenital ocular anomalies , 310–312
Congenital spinal and vertebral 
malformations , 313–314
Congestive heart failure (CHF) , 
315–318
in aortic stenosis, 106
in aortic thromboembolism, 109, 110
in arrhythmogenic right ventricular 
cardiomyopathy, 226

1592  Index  
in arteriovenous fistulas/
malformations, 112
in ascites, 121
in atrial premature complexes, 
139–140
in atrial septal defect, 141
in atrial standstill, 142–143
in atrial wall tear, 144, 145
in atrioventricular valve dysplasia, 
154, 155
in atrioventricular valvular stenosis, 
156, 157
in dilated cardiomyopathy, 229, 
230, 232
in endomyocardial diseases of cats, 448
in hypertrophic cardiomyopathy, 235, 
236, 238
in infective endocarditis, 445, 446
left‐sided, 315–316
in myxomatous mitral valve disease, 
951, 952–953
in patent ductus arteriosus, 1049, 
1050, 1051
in pulmonic stenosis, 1153, 1154
in restrictive cardiomyopathy, 241–242
right‐sided, 317–318
sinus tachycardia, 1259
in supraventricular tachycardia, 1307, 
1308
in ventricular septal defect, 1412
Conjunctival neoplasia, 319, 322
Conjunctivitis , 319–322
in cats, 319–320
chlamydiosis/chlamydial, 258–259, 320
in dogs, 321–322
mycoplasmal, 320
neonatal, 994–995
Conocybe  mushroom poisoning, 916
Constipation , 323–324
Constrictive pericardial disease, 1058
Contact dermatitis , 325
nasal, 956
Contact mucositis/mucosal 
ulceration, 1297
Continuous muscle fiber activity 
(CMFA), 945
Contrast agents, nephrotoxic, 974
Controlled drugs, 1571
Convallaria majalis,  1454
Conversion tables, 1569–1570
Convulsions. See Seizures
Cooling measures, for heat stroke and 
hyperthermia, 589–590
Coonhound
coonhound paralysis, 326
hemophilia B, 286–287
methemoglobinemia, 904Coonhound paralysis , 326–327
Copper associated hepatopathy 
(CuAH) , 328–331
chronic hepatitis, 622
cirrhosis/fibrosis of liver, 279, 280
Copper deficiency, 87
Copper‐restricted diets, 330
Copperhead snake envenomation, 
1266–1267
Coprophagia , 332–333
Coral snake envenomation , 1265
Corgi. See Welsh corgi
Coriolus versicolor  bioactive extract, 594, 
595, 596, 599
Cori’s disease (glycogen debranching 
Corneal and scleral lacerations , 
334–335
Corneal degenerations and 
infiltrates , 336
Corneal dystrophies , 337
Corneal epithelial defects, spontaneous 
chronic (SCCED), 798, 799
Corneal opacities , 336–337
Corneal sequestrum, in cats , 338
conjunctivitis, 320
nonulcerative keratitis, 796, 797
Corneal ulceration, 798–799
Cornish Rex, blood type, 1499
Coronavirus infections, canine , 208
Corrosives, household, 1461–1462
Corticosteroid hepatopathy. See 
Glycogen‐type vacuolar 
hepatopathy
Corticosteroid myopathy, 941, 942
Corticosteroid responsive shaker/
tremor syndrome , 1240
Corticosteroids (glucocorticoids). See also  
Budesonide; Dexamethasone; 
Hyperadrenocorticism; 
Methylprednisolone; 
Prednisolone; Prednisone; 
T riamcinolone
for acne, 14, 15
for acute respiratory distress 
syndrome, 26
for blastomycosis, 181
for blind quiet eye, 184, 185
for brain tumors, 129, 195for cataracts, 246
for cervical spondylomyelopathy, 253
syndrome, 263–264
for chronic hepatitis, 624, 625
for contact dermatitis, 325
for depigmenting disorders, 373
for eosinophilic 
meningoencephalomyelitis, 896
for eosinophilic pneumonia, 1089
for esophagitis, 470
for flea bite hypersensitivity, 538
gastroduodenal ulceration/erosion due 
to, 552
for glucagonoma, 568–569
for hypoadrenocorticism, 720
for hypopituitarism, 741
for inflammatory bowel disease, 
557, 772
for inflammatory/immune colitis, 301
for inflammatory myopathies, 
938–939, 941
for insoluble oxalate plant toxicosis, 775
for insulinoma, 777
for keratitis, 795, 797
perforation, 811Congestive heart failure (CHF)  (cont’d )

Index  1593
for lupus erythematosus, 844, 846
for meningioma, 892, 893
for meningitis/meningoencephalitis/
meningomyelitis, 895
for muscular dystrophy, 947
for necrotizing encephalitis, 963
for optic neuritis and papilledema, 998
for orbital disease, 1002
for polyneuropathies, 1108
for pruritus, 1142, 1143
for pulmonary edema, 1150
for puppy strangles, 1159
for rectal stricture, 1181
for retinal detachment, 1196, 1198
for seizures/status epilepticus, 1228
for shaker/tremor syndrome, 1240
for spinal cord trauma, 931
for steroid‐responsive meningitis‐
arteritis, 1294
for sun‐induced dermatoses, 384
1306
for third eyelid protrusion, 1324
for tremors, 1356
for vesiculopustular dermatoses, 386
Corticotropin. See ACTH
Cortisol, reference ranges, 1445
Cortisol  : creatinine ratio, urinary, 1445
Cosequin (glucosamine and chondroitin 
sulfate), 116, 1458Cosyntropin, 1444
Coton de T ulear
Cough , 339–340
asthma, bronchitis—cats, 127
in canine infectious respiratory disease, 
215
in chronic bronchitis, 200
Cough suppressants. See Antitussives/
cough suppressants
Counter‐conditioning
for canine aggression, 43, 44, 
47–48, 51
for fears, phobias, and anxieties, 494, 
496
for kitten behavior problems, 802
for safe patient handling, 490, 492
for separation anxiety syndrome, 1232
1333
Counters, puppies getting on, 1156
Coxiella burnetii,  1176
Cranberry extract, 839, 1373
Cranial cruciate ligament disease , 
342–343
Craniomandibular osteopathy , 341
Crenosoma vulpis,  1190–1191
Cricopharyngeal muscle dysfunction, 
422, 423, 424
Crofab antivenin, 1267
Crossmatch , 1512–1513
Crotalid antivenin, 1267, 1449
Crotalus  spp. envenomation, 1266–1267
Cruciate ligament disease, cranial , 
342–343
Cryoprecipitate
for coagulation factor deficiency, 287
for coagulopathy of liver disease, 288
for von Willebrand disease, 1429
Cryotherapy
post‐surgical, 1047
for shoulder problems, 1248
Cryptococcosis , 344–345
upper respiratory tract, 524
Cryptococcus gattii,  344, 360
Cryptococcus neoformans,  344, 360
Cryptorchidism , 346
Sertoli cell tumor, 1237
Cryptosporidiosis , 347
Cryptosporidium  spp., 294, 347
Crystalluria , 348–349. See also  
UrolithiasisCtenocephalides felis,  538
Curly‐coated retriever
exercise‐induced weakness/
collapse, 478
Currant toxicosis, 577
Curtain sign, 1544–1545
Cushing’s syndrome. See 
Hyperadrenocorticism
Cutaneous drug eruptions , 350
Cutaneous epitheliotropic lymphoma 
(CEL) , 858
alopecia, 65, 67
depigmentation, 372
Cutaneous flushing syndrome, 1043
Cutaneous histiocytoma, 650, 651
Cutaneous histiocytosis , 652
Cutaneous horns, 384
Cutaneous leishmaniosis , 825–826
Cutaneous lupus erythematosus. See 
Discoid lupus erythematosus
Cutaneous mycoses, deep , 360–361
Cutaneous neoplasia. See Skin tumors
Cutaneous vasculitis , 1400
Cuterebriasis ( Cuterebra  infections) , 
351
encephalitis, 444
ischemic encephalopathy, 512–513
respiratory tract, 1190–1191
Cyanobacterial toxicosis, 187
Cyanocobalamin. See also  Cobalamin
for chronic diarrhea, 404, 406
Cyanosis , 352–353
Cycad (sago) palm toxicosis , 1213
Cyclamen persicum,  1455
Cyclic flank alopecia, 67
Cyclic hematopoiesis , 354
Cyclitis, 98, 100
Cyclooxygenase‐2 (COX‐2) inhibitors. 
See also  Deracoxib; Firocoxib; 
Robenacoxib
for osteoarthritis, 115
for prostatic carcinoma, 1134–1135
toxicosis, 981–982
Cyclophosphamide
599
for mammary tumors, 866
for nerve sheath tumors, 976
for pain (acute, chronic, and 
postoperative), 1021

1594  Index  
for squamous cell carcinoma, 1286
for thymoma, 1335
Cycloplegics, 99, 101, 742
Cyclosporine (CsA/CyA)
for allergic dermatitis, 66
for aplastic anemia, 82
for claw and clawfold disorders, 283
for corneal opacities, 336, 337
for eosinophilic granuloma complex, 452
for histiocytic diseases, 651
406, 772
301, 302
for perianal fistula, 1057
for pruritus, 1143
for sebaceous adenitis, 380, 1224
dermatoses, 381, 383
Cyfluthrin toxicosis, 1170
Cylert. See Pemoline toxicosis
Cylindruria , 355
Cyphenothrin toxicosis, 1170
Cyproheptadine, 1449
for anorexia, 95for antidepressant toxicosis, 102, 105
Cystadenocarcinoma
bile duct, 173
renal, 36, 308, 309
Cystic endometrial hyperplasia (CEH)
pyometra, 1165, 1166
spontaneous abortion, 2, 3, 4, 5
Cystine crystalluria, 348, 349
Cystine urolithiasis , 1376–1377
Cystinuria, 308, 1376
Cystitis
feline idiopathic (FIC), 504–505
polypoid, 1111–1112
Cystocentesis , 1514–1516
Cystoisospora  spp., 294, 1523
Cytarabine. See Cytosine arabinoside
Cytauxzoon felis,  161, 356
Cytauxzoonosis , 356
Cytochrome b5 reductase deficiency, 904, 
905
Cytopoint. See Lokivetmab
Cytosine arabinoside (cytarabine)
Cytotoxic mushroom poisoning, 
916–919
Cytoxan. See Cyclophosphamide
D
Dacarbazine, 599, 858
Dachshund. See also  Long‐haired 
dachshund; Miniature 
dachshund; Smooth‐haired 
miniature dachshund; Wirehaired 
dachshund
diabetes mellitus, 395, 399
ectodermal defects, 376
epilepsy, 454eyelash disorders, 482
intervertebral disc disease, 130, 
781, 784
linear IgA dermatosis, 385
myelomalacia, 929
narcolepsy/cataplexy, 954
nasopharyngeal stenosis, 960
oronasal fistula, 1005
puppy strangles, 1159
skin tumors, 378, 886
urolithiasis/crystalluria, 308, 348, 
1376, 1568
vasculitis, 1400
vitiligo, 372, 956
Dacryocystitis, 456, 457
Daffodil, 1455
Dalmatian
acute abdomen, 18
acute respiratory distress syndrome, 25
cervical spondylomyelopathy, 252, 961
328, 329, 622
crossmatching, 1512
idioventricular rhythm, 754
laryngeal paralysis/polyneuropathy 
complex, 812, 1107, 1295Cyclophosphamide ( cont’d )

Index  1595
mitral valve dysplasia, 154
reflex myoclonus, 937, 946
skin tumors, 1289
1383, 1568
Dalteparin
for cardiomyopathy, 230
1152
Dandie Dinmont terrier
Dantrolene, 1449
Daphne (Daphne mezereum),  1453
Dapsone
for brown recluse spider 
envenomation, 1275
for rhinosporidiosis, 460
Darbepoetin
for chronic kidney disease, 80,  
88, 275
Datura stramonium,  1456
Day blindness, 310, 311
Daytrana. See Methylphenidate
Dazzle reflex, 1508
DC (electrical) cardioversion, 136–137
DCM1/NCSU/PDK4  gene, 232, 1415
DCM2/NCSU  gene, 232, 1415
DDAVP . See Desmopressin
op’‐DDD. See Mitotane
Deafness , 357–358
Deciduous teeth, persistent , 359
Declawing, 388, 802
Decongestants, nasal, 502, 959, 1269
Decoquinate, for hepatozoonosis, 645
Deep cutaneous mycoses , 360–361
Defecation, inappropriate, 657–662. 
See also  Fecal marking
in cats, 657–660
in dogs, 661–662
Defensive aggression, in cats, 56
Defensive behaviors, in kittens, 801, 802
Deferoxamine, 791, 1449
Defibrillation, 1405Degenerative joint disease (DJD). See 
Osteoarthritis
Degenerative myelopathy, canine , 
209–210
Delmadinone acetate, 168, 1134
Delphinium, 1453
Deltamethrin toxicosis, 1170
Demecarium bromide, 565, 827
Demodex canis,  362
Demodex cati,  65, 362
Demodex cornei,  362
Demodex gatoi,  65, 362
Demodex injai,  182, 362
Demodicosis , 362–363
acne, 14
alopecia, 65, 66, 67, 68
nasal, 956
Demyelinating neuropathies, 1107
Dens hypoplasia/aplasia, 132
Dens‐in‐dente, 1342
Dental caries , 364–365
Dental malocclusion , 862–863
Dentigerous cyst , 366
Dentinogenesis imperfecta, 409, 900
Dentoalveolar injuries, traumatic , 
1353–1354
Depigmenting dermatoses , 372–373
Depo‐Medrol. See Methylprednisolone
L‐Deprenyl. See Selegiline
Deracoxib
for osteoarthritis, 116, 1471
Dermacentor andersoni,  1204, 1336
Dermacentor reticulatus,  161
Dermacentor variabilis,  356, 1204, 1336, 
1338
Dermatitis
acral lick, 16
allergic. See Allergic dermatitis
atopic, 134–135
contact. See Contact dermatitis
flea bite, 538–539
Malassezia,  860
nasal solar, 372, 384, 956, 957Pelodera,  381
plastic dish, 373, 956
psychogenic, 304–305
solar, 384
superficial necrolytic. See Superficial 
necrolytic dermatitis
Dermatofibrosis, nodular, 36, 1044
Dermatologic adverse food reactions , 
540–541
Dermatomyositis , 367–368, 940–941
nasal, 956
pustules/vesicles, 385
Dermatophilosis , 369
Dermatophytosis , 370–371
Dermatoses , 372–387
depigmenting disorders, 372–373
erosive or ulcerative, 374–375
exfoliative, 376–377
nasal, in dogs, 956–957
neoplastic. See Skin tumors
papulonodular, 380–381
sterile nodular/granulomatous, 
382–383
sun‐induced, 384
vesiculopustular, 385–386
viral (non‐papillomatosis), 387
Dermoids, ocular, 310
DES. See Diethylstilbestrol
Descemetocele, 798, 799
Desensitization
47–48, 51
496
1333
Deslorelin
for ovulatory failure, 1020
for prostatic disease, 168, 1130, 1134
Desmopressin (DDAVP)
for diabetes insipidus, 391
for thrombocytopenia, 1072
for von Willebrand disease, 460, 1430
Desomorphine toxicosis, 996–997
Desoxycorticosterone pivalate (DOCP), 
720–721
Destructive behavior , 388–390
in cats, 388
in dogs, 389–390

1596  Index  
Detemir insulin, 400
Detergents, toxicity, 1460–1461
Detrusor atony, 430
Detrusor hyperreflexia, 766
Devon Rex
alopecia, 65
hepatic amyloidosis, 609
muscular dystrophy, 947
Dexamethasone
for blood transfusion reactions, 186
1208
for chronic hepatitis, 625
for encephalitis, 443, 444
dysplasia, 640
meningomyelitis, 895for meningoencephalomyelitis of 
for papilledema, 998
for pemphigus, 1056
1228
for termination of pregnancy, 6–7
Dexamethasone suppression test
high dose (HDDST), 1444
low dose (LDDST), 1444
Dexedrine. See Dextroamphetamine
Dexmedetomidine
1333–1334
Dexmethylphenidate (ADD/ADHD 
medication) toxicosis, 72–73
Dexrazoxane, 857
Dextroamphetamine (amphetamine) 
toxicosis, 72–73
Dextrose solutions
for diabetic hyperosmolar 
for diabetic ketoacidosis, 396
for dystocia, 429
for ethanol toxicosis, 473
for hyperkalemia, 23, 683
for hypoglycemia, 728
for neonates, 964
for portal hypertension, 702
for pregnancy toxemia, 1125
for xylitol toxicosis, 1436
Diabetes insipidus , 391–392
congenital nephrogenic, 308
modified water deprivation test, 
1444–1445
polyuria and polydipsia, 1113, 1114Diabetes mellitus (DM) , 393–400
acromegaly in cats, 700
alopecia in cats, 66
canine uncomplicated, 399–400
feline uncomplicated, 397–398
gestational, 561
glucose curve, 1530–1532
glucosuria, 570, 571
hyperglycemia, 681–682
with hyperosmolar hyperglycemic 
state, 393–394
with ketoacidosis, 395–396
polyneuropathy, 1107, 1108
retinal hemorrhage, 1197
Diabetic ketoacidosis , 395–396
Diagnostic peritoneal lavage (DPL), 
1476–1478
Diaphragmatic hernia , 401
peritoneopericardial, 1068
Diarrhea.  See also  Colitis; Gastroenteritis
acute, 21–22
acute hemorrhagic diarrhea syndrome, 
554–555
antibiotic responsive, 402
in campylobacteriosis, 206
in canine coronavirus infections, 208
canine infectious, 213–214
in canine parvovirus infection, 217
chronic canine, 405–406
chronic feline, 403–404
in clostridial enterotoxicosis, 284
in colitis and proctitis, 300–301
feline infectious, 508–509
fiber‐responsive large bowel, 528–529
tylosin responsive, 1262
Diazepam
for brain tumors, 129
1208
for carbon monoxide toxicosis, 223

Index  1597
for feline ischemic encephalopathy, 
513
for genetic epilepsy in dogs, 455
for mycotoxicosis, 927
for nystagmus, 985
for pyrethrin/pyrethroid toxicosis, 
1170
for salt toxicosis, 1220
1228
1334
Diazoxide, 777
Dicentra  spp., 1452
Diclofenac, 99, 101, 742
Dicloxacillin, 1293
Dieffenbachia  ingestion, 775
Diencephalic syndrome, 1043
Dietary supplements/nutraceuticals
for canine aggression, 59, 60
for cognitive dysfunction syndrome, 
295–296
495, 497
for kitten behavior problems, 802, 
804
for liver fluke infestation, 837
for puppy socialization, 1158
1334for urolithiasis, 1373–1374, 1376
Diethylstilbestrol (DES)
for urinary incontinence, 766, 1054
Difenacoum toxicosis, 1206
Difethialone toxicosis, 1206
Digibind. See Digoxin immune Fab 
fragments
Digital melanocytic tumors , 888
Digital squamous cell carcinoma , 1283
Digoxin
for atrial fibrillation, 137, 138
for atrioventricular valve disease, 155, 
157, 158, 953
for cardiomyopathy, 230, 234
for endomyocardial diseases of 
cats, 448
Digoxin immune Fab fragments, 1449
225
for digoxin toxicity, 407
Digoxin toxicity , 407
Dihydrostreptomycin, 203
Dihydrotachysterol (DHT), 41, 737
2,8‐Dihydroxyadenine crystals, urinary, 
348, 349
1,25 Dihydroxycholecalciferol. See 
Diisocyanate glues , 408
Dilacerated tooth, 1342
Dilated cardiomyopathy , 229–234
in cats, 229–231
in dogs, 232–234
ventricular tachycardia, 1415
Dilinolylphosphatidylcholine (DLPC). 
See Polyunsaturated 
phosphatidylcholine
Diltiazem
157
for dilated cardiomyopathy, 230, 
233–234
for restrictive cardiomyopathy, 242for sinus tachycardia, 1259
Dimenhydrinate, 1422
Dimercaprol (BAL), 1450
2‐3 Dimercaptosuccinic acid. See 
Succimer
Dimethylsulfoxide (DMSO)
for calcinosis cutis, 383
Diminazene, for babesiosis, 161, 
162, 460
Dinoprost. See Prostaglandin F2αDinotefuran/pyriproxyfen, 538–539
Dioctophyma renale,  1370–1371
Dioctyl calcium/sodium sulfosuccinate. 
See Docusate sodium/calcium
Diphacinone toxicosis, 1206, 1207
Diphenhydramine
for cuterebriasis, 444
513
for lymphoma, 857
for vomiting, 28
Diphenoxylate, 301, 764
Diphyllobothrium,  1317
Dipivefrin, 718
Dipylidium caninum,  1317, 1523
Dipyrone, 527
Dirofilaria immitis  infections. See 
Heartworm disease
Disaster and emergency response, 1571
Discoid lupus erythematosus (DLE) , 
844
nasal involvement, 956, 957
Discolored tooth/teeth , 409–410
Discospondylitis , 411–412
Disease‐modifying osteoarthritis agents 
(DMOAs), 116, 1472. See also  
Disease outbreaks, 1571
Disinfectants, toxic exposures, 
1462–1463
Disorders of sexual development 
(DSD) , 1238–1239
coagulation (DIC) , 413–414
heat stroke, 589
anemia—immune‐mediated, 84
cytauxzoonosis, 356

1598  Index  
hemangiosarcoma, spleen and liver, 589
hypercoagulability, 677
in coagulation factor deficiency, 288
in infectious canine hepatitis, 628
in liver disease, 288
paraneoplastic, 1043
sepsis, 1235
shock, septic, 1245
snake venom toxicosis—pit 
vipers, 1266
Disseminated invasive aspergillosis , 
122–123
Distemper, canine , 211–212
Distichiasis , 482
Diuretics
for arteriovenous malformation of the 
liver, 114
for ascites, 121, 281, 417, 702, 1116
for canine pregnancy edema, 1124
for congestive heart failure, 315–316, 
318
for oliguria, 992
for peripheral edema, 1066
for pleural effusion, 1083
for poisoning, 1099
for valvular heart disease, 157, 
952, 953
DMSO. See Dimethylsulfoxide
DNM1  gene mutation, 478, 479, 907
Doberman pinscher
acne, 15
anemia, 84
arthritis, 118, 1103
atrioventricular block, 146, 152
brain tumors, 194
cervical spondylomyelopathy, 130, 
252, 253, 961
color‐dilution alopecia, 67, 376
compulsive disorders, 306congestive heart failure, 316
conjunctivitis, 321
deep cutaneous mycoses, 360
234, 1415, 1416, 1417
fungal pneumonia, 1090
glomerulopathy, 308, 566, 1138
hepatic disease, 279, 328, 329, 622, 
701, 752
intervertebral disc disease, 781
ocular anomalies, 310
renal agenesis, 308
seborrhea (primary idiopathic), 376
spinal stenosis, 313
ventricular premature complexes, 
1409, 1410
ventricular tachycardia, 1415, 1416, 
1417
1327, 1429
Dobutamine
for cardiomyopathy, 230, 233, 242
Docusate sodium/calcium
for dyschezia and hematochezia, 420for megacolon, 882
for rectal and anal prolapse, 1180
for rectoanal polyps, 1182
Dog erythrocyte antigen (DEA), 1498, 
1499
Blood transfusion reactions, 186
Dogue de Bordeaux
tricuspid valve dysplasia, 154, 156
Dolasetron
Doll’s eye plant, 1452
Domestic longhair cat
acquired portosystemic shunting, 
1115
hyperthyroidism, 709
leukocyte adhesion deficiency, 831
mammary gland tumors, 865
Domestic shorthair (DSH) cat
anemia, 84, 90
blood type, 1498, 1499
chronic bronchitis, 200
hyperoxaluria, 308, 1107
hyperparathyroidism, 694
lysosomal storage disease, 689, 
859, 1107
meningioma, 891
osteosarcoma, 1011
paraneoplastic alopecia, 518
urolithiasis/nephrolithiasis, 970, 1376
xanthinuria, 308
Dominance (conflict) aggression, in 
dogs, 58
Domperidone, 549, 826
Dopamine
for atrioventricular block, 153Disseminated intravascular coagulation 
(DIC)  (cont’d )

Index  1599
Dopamine agonists
Doramectin
for notoedric mange, 983
for sarcoptic mange, 1221
Dorzolamide
Doxapram hydrochloride, 966
Doxepin, 16
Doxorubicin
for adenocarcinoma, 31
cardiotoxicity, 594, 595, 596, 599
598–599
861
for squamous cell carcinoma, 1286, 
1291
for transmissible venereal tumors, 1352
Doxycycline
for aspergillosis, 125
for brucellosis, 203
for dermatomyositis, 368
for ehrlichiosis and anaplasmosis, 437
for epididymitis and orchitis, 453for feline calicivirus infection, 500
525
for heartworm disease, 586, 588
for lupus erythematosus, 844
for mycoplasmosis, 607, 925
for retinal hemorrhage, 1198
1205
for salmon poisoning disease, 1216
for sebaceous adenitis, 1224
Drentse patrijshond
Dried blood pseudo‐urolithiasis , 1378
Drontal Plus, 167, 301
Drowning  (near drowning) , 415
Drug eruptions, cutaneous , 350
Drug‐induced crystalluria, 349
Drug‐induced nephrotoxicity , 
974–975
Drugs
animal, 1571
controlled, 1571
useful, 1449–1451
Dry cell battery toxicosis, 166
Dry lung, 1545
Ductal plate malformation (DPM) , 
416–418
cirrhosis and fibrosis of liver, 279, 280
extrahepatic bile duct obstruction, 174
Ductopenia, feline, 262, 264
Dutch kooiker
Dutch Tervuren shepherd, gastric 
adenocarcinoma, 39
Dwarfism, pituitary, 741, 900–901
Dysautonomia , 419
polyneuropathies, 1107, 1108
third eyelid protrusion, 1323Dyschezia , 420–421
Dysmetria , 689–690
Dysphagia , 422–424
Dyspnea , 425–427
Dysrexia, 94
Dystocia , 428–429
Dystrophin deficiency, 947
Dysuria , 430–431
E
Ear canal tumors, 251, 1284
Ear cleansing, otitis externa, 1014
Ear mites , 432
Ear tumors
ceruminous gland adenocarcinoma, 
251
squamous cell carcinoma, 1284
Ebstein’s anomaly , 154
Ecchymosis , 1072–1073
Echinacea purpurea,  1457
Echinococcus,  1317
Eclampsia , 433
Ecstasy (MDMA) toxicosis, 758
Ectopic cilia , 482
Ectopic ureter , 434
Ectropion , 435
Edema
in canine pregnancy, 1123–1124
hypoalbuminemia, 722
peripheral, 1065–1066
Edetate calcium disodium. See Calcium 
disodium EDTA
EDTA. See also  Calcium disodium 
EDTA
Effusions, analysis, 1527–1529
ascites, 120
pleural effusion, 1082
Egyptian mau cat
Ehlers–Danlos syndrome, 793
Ehrlichiosis , 436–437
Eisenmenger physiology, 352
Elapid snake antivenin, 1265, 1449
Elapid snake envenomation, 1265
Elbow dysplasia , 438–439
Elbow incongruity, 438–439
Elbow malalignment syndrome, 96, 97
Electric cord injury , 440
Electrical (DC) cardioversion,  
136–137
Electrocardiography , 1517–1519
normal values, 1448
Elizabethan collar, for veterinary visits, 
493
Elk antler velvet, 649

1600  Index  
Emesis, induced, 1098
for antidepressant toxicosis, 102, 
104–105
Emodepside, 655, 1212, 1317
Emollients, for exfoliative 
dermatoses, 377
Enalapril
for cardiomyopathy, 230, 233, 
236, 242
316, 318
for valvular heart disease, 155, 
157, 952
Enamel hypoplasia/
hypocalcification , 441
Encephalitis , 442–443
necrotizing, 963
secondary to parasitic migration, 444
Endocardial fibroelastosis, feline, 
447, 448
Endocardial splitting, atrial wall tear, 144
Endocarditis, infective , 445–446
Endocrine bone disorders , 900–901
Endocrine myopathies , 942–943
Endocrine testing, 1444–1446
protocols, 1444–1445
unit conversion table, 1446
Endogenous lipid pneumonia (EnLP), 
1092, 1093
Endometrial hyperplasia, cystic. See 
Cystic endometrial hyperplasia
Endomyocardial diseases – cats , 
447–448
Endomyocarditis, feline, 447–448
Endothelin receptor antagonists, 705
Endotracheal wash (ETW), 1553, 1554Enemas
Energy requirements, 986, 1432
English bull terrier. See also  Bull terrier
English bulldog. See also  Bulldog
acne, 15
cardiomyopathy, 227, 1415
brachycephalic airway syndrome, 190, 
1295
cystinuria, 308, 1376, 1568
eyelid/eyelash problems, 182, 482
hyperuricuria, 308
pemphigus foliaceus, 1055
Sjögren‐like syndrome, 1260
spinal malformations, 313, 1276
splenic torsion, 1278
tetralogy of Fallot, 1322
1376, 1383, 1568
1393, 1394
English cocker spaniel. See also  Cocker 
spaniel
aggression, 47, 58
anal sac adenocarcinoma, 29, 77
kidney disease, 274, 308, 1138
pancreatitis, 1029, 1030
retinal degeneration, 1193sexual development disorders, 1238
English foxhound
proteinuria, 1138
English holly, 1453
English ivy, 1453
English pointer. See also  Pointer
English setter
lysosomal storage disease, 689, 859
taurine deficiency, 239
English shepherd, ivermectin 
sensitivity, 792
English springer spaniel. See also  Springer 
spaniel
aggression, 46, 47, 58
anemia, 84, 90, 1548
atrial standstill, 142, 754
glycogen storage disease, 573
1107
phosphofructokinase deficiency, 948, 
1078
retinal dysplasia, 310, 1193, 1195, 
1197
Rocky Mountain spotted fever, 1204
spermatozoal abnormalities, 1273
1393, 1394
English toy spaniel, 
pseudomacrothrombocytopenia, 
1145
Enilconazole, 125, 370, 371, 460

Index  1601
Enophthalmos , 1001–1002
third eyelid protrusion, 1323
Enoxaparin
for cardiomyopathy, 230, 242
for disseminated intravascular 
coagulation, 288
for infectious canine hepatitis, 628
Enrofloxacin
for colitis, 301, 302, 303
513
ocular toxicity, 1193
for prostatic disease, 1130
1205
Entamoeba histolytica,  300
Enteral feeding
for canine parvovirus infection, 218
Entropion , 449, 482
Entyce. See CapromorelinEosinophilia , 450
Eosinophilic conjunctivitis, 320
Eosinophilic dermatitis with edema, 350
Eosinophilic folliculitis and furunculosis, 
canine, 956
Eosinophilic gastroenteritis , 556–557
Eosinophilic granuloma
in cats, 451
in dogs (EGD), 382, 383, 451–452
Eosinophilic granuloma complex , 
451–452
Eosinophilic keratitis, feline , 795, 796, 
797
Eosinophilic 
meningoencephalomyelitis , 896
Eosinophilic plaque, feline, 451
Eosinophilic pneumonia , 1088–1089
Eosinophilic pustulosis, sterile, 385, 386
Eosinophilic skin disease, feline, 
451–452
Ephedrine, 959
Epididymitis , 453
Epidural anesthesia, 429
Epilepsy . See also  Seizures
in cats, 1225–1226
definitions and classification, 
1473–1474
in dogs, 1227–1229
genetic, in dogs, 454–455
Epileptoid cramping syndrome, canine, 
907, 946
for anaphylaxis, 79, 186, 1066
244, 1406, 1413
for neonatal resuscitation, 966
Epiphora , 456–457
Epipremnum  spp., 775
Episcleritis , 458
Episodic falling syndrome, 907, 946
Episodic muscle hypertonicity 
syndromes, 946
Epistaxis , 459–461
in nasal adenocarcinoma, 32, 33
Epitheliotropic lymphoma. See 
Cutaneous epitheliotropic 
lymphoma
Epoetin alfa. See Erythropoietin
Epsilon‐aminocaproic acid (aminocaproic 
acid), 288, 1244, 1328
Epsiprantel, 1317
Epulides, feline, 988–989
Ergocalciferol, 737
Ergonovine, 1304
Erosive dermatoses , 374–375
Erosive polyarthritis
of greyhounds (EPG), 1101
immune‐mediated, 1101–1102Erythema multiforme (EM), 350, 372
Erythrocytosis , 462–463
Erythromycin
for corneal sequestrum, 797
for infectious diarrhea, 214, 509
Erythropoietin (EPO)
for anemia of chronic kidney disease, 
80, 88
excess, 462–463
for pancytopenia, 1032
Escherichia coli,  298–299, 303, 838
Esmolol
for atrial fibrillation, 137
172
for supraventricular tachycardia, 
1308
for ventricular tachycardia, 1417
Esomeprazole, 890
Esophageal diverticula , 464
Esophageal foreign bodies , 465–466
Esophageal stricture , 467–468
Esophagitis , 469–471
Essential fatty acids. See Omega‐3 fatty 
acids
Essential oils toxicosis , 472
Estriol, 434, 766, 1054
Estrogens
toxicity. See Hyperestrogenism
for urinary incontinence, 766
Estrus, 196, 768
Ethambutol, 923
Ethanol, for ethylene glycol toxicosis, 
475, 1450
Ethanol toxicosis , 473
Ethyl lactate, 377
Ethylene diamine tetra‐acetate. See 
EDTA
Ethylene glycol toxicosis , 474–475
Etodolac

1602  Index  
Etofenprox
for flea control, 539
toxicosis, 1170
Etretinate, 1284, 1288
Eucalyptus oil, 472
Eucoleus  (formerly Capillaria ) aerophilus,  
Eucoleus  (formerly Capillaria ) boehmi,  
Euphorbia pulcherrima,  1456
Eurasian, exocrine pancreatic 
insufficiency, 480
European shorthair cat, nephrolithiasis, 
970
Eurytrema procyonis,  836
Evening primrose oil, 1224
Excessive moderator bands (EMBs), 
447, 448
Excessive vocalization and waking at 
night , 476–477
Excitement urination in dogs ,  
1305
Exercise‐induced weakness/collapse 
in Labrador retrievers ,  
478–479
Exfoliative dermatitis, paraneoplastic, 
1043
Exfoliative dermatoses , 376–377
Exfoliative erythroderma, 350
Exocrine pancreatic insufficiency , 
480–481
Exophthalmos , 1001–1002
Exotic shorthair cat
Extracorporeal shock wave lithotripsy 
(ESWL), 971, 1363
Extrahepatic bile duct obstruction. See 
Bile duct obstruction 
(extrahepatic)
Extraocular myositis , 938–939
Exudates, 1527, 1528, 1529
Eye covers, for anxious patients, 493
Eye exam, complete, 1507–1511
Eye trauma, 334–335
Eyelash disorders , 482
Eyelid disorders. See also  Ectropion; 
Entropion; Third eyelid
blepharitis, 182–183
congenital, 182, 183, 310, 482
epiphora, 456–457
EZ Nabber, 491F
Fabric chewing and sucking, compulsive, 
304–305
Facial discoid lupus erythematosus, 844
Facial nerve paresis and paralysis , 
483–484
Factor XII deficiency, 286
Fading syndrome , 964–965
Fahrenheit to Celsius conversion table, 
1569
Failure of passive transfer, 966
Falling, episodic, 907, 946
Fallot’s tetralogy , 1322
False pregnancy , 485–486
Famciclovir
for feline herpesvirus infection, 320, 
502, 797, 799
for viral dermatoses, 387
Familial shar‐pei fever. See Shar‐pei fever, 
familial
Famotidine
in acute abdomen, 20
in acute hepatic failure, 615
in acute kidney injury, 24
in anaphylaxis, 79
in arteriovenous malformation of 
liver, 114
in battery toxicosis, 166
in bile peritonitis, 178
in bilious vomiting syndrome, 179
in calcipotriene/calcipotriol 
in cardiac glycoside plant toxicosis, 
225
in cholecalciferol rodenticide toxicosis, 
1210
in diisocyanate glue exposure, 408
in esophagitis, 470, 471
in gastroduodenal ulceration/erosion, 
553, 890
in Helicobacter  infection, 592
in hematemesis, 601
in hiatal hernia, 646
in infectious canine hepatitis, 629
in meningoencephalomyelitis of 
in metabolic alkalosis, 64
in metformin toxicosis, 903
in NSAID toxicosis, 982
in peritonitis, 1070
in physalopterosis, 1079
in quadrigeminal cyst, 1177
in rodenticide toxicosis, 1211
in spondylosis deformans, 1281
in vomiting, 28, 1427Fanconi syndrome , 489
congenital and developmental renal 
disease, 308, 309
copper associated hepatopathy, 
328, 330
metabolic acidosis, 12
Fat emulsion, intravenous. See 
Intravenous lipid emulsion
Fatty acids. See also  Omega‐3 fatty acids
Fear, 490–497. See also  Anxiety;  
Phobias
in cats, 490–491, 494–495
in dogs, 492–493, 496–497
in kittens, 801
in veterinary visits, 490–493
Fear aggression
in cats, 49, 53, 56
in dogs, 44, 58
Fear urination, in dogs, 1305
Febantel, 167, 562, 1435
Fecal direct smear and cytology , 
1520–1521
Fecal flotation , 1522–1524
Fecal incontinence , 763–764
Fecal marking
in cats, 657, 659
in dogs, 872
Fecal microbiota transplant, 772
Felbamate, 455
Feline alveolar osteitis , 498
Feline calicivirus infection , 499–500
vaccines, 500
virulent systemic disease (VSD), 
499, 524
Feline chronic gingivostomatitis 
(FCGS) , 519–520
Feline congenital porphyria, 90
Feline coronavirus (FCoV), 510
Feline enteric coronavirus (FECV), 510, 
511
Feline eosinophilic keratitis , 795, 796, 
797
Feline hepatic lipidosis. See Hepatic 
lipidosis
Feline herpesvirus infection (FHV‐1) , 
501–502
conjunctivitis, 319, 320
cutaneous, 387
eosinophilic keratitis, 795, 796, 797
upper respiratory tract, 524, 525
vaccines, 502
Feline hyperesthesia syndrome , 503
compulsive disorders, 304, 305
Feline idiopathic cystitis (FIC), 504–505Etodolac ( cont’d )

Index  1603
Feline idiopathic lower urinary tract 
disease (FLUTD) , 504–505
Feline immunodeficiency virus (FIV) 
infection , 506–507
Feline inductive odontogenic tumor 
(FIOT), 988
Feline infectious diarrhea , 508–509
Feline infectious peritonitis (FIP) , 
510–511
Feline infectious peritonitis virus (FIPV), 
2, 510, 511
Feline injection site sarcoma (FISS), 
1270, 1271
Feline ischemic encephalopathy (FIE) , 
512–513
Feline leukemia virus (FeLV) infection , 
514–515
anemia, 89
lymphoma, 514, 515, 854, 855
myelodysplastic syndromes, 928
myeloproliferative disorders, 932
vaccines, 515
Feline odontoclastic resorptive lesions 
(FORL), 522–523
Feline panleukopenia , 516–517
cerebellar hypoplasia, 130, 248
vaccines, 517
Feline paraneoplastic alopecia , 518, 
1043
Feline parvovirus (FPV), 516–517
Feline periosteal proliferative 
polyarthritis (FPPP), 1101, 1102
Feline progressive histiocytosis (FPH), 
650, 651, 652
Feline pulmonary Langerhans cell 
histiocytosis (FPLCH), 650, 651
Feline stomatitis , 519–520
Feline symmetrical alopecia , 521
Feline thymoma-associated exfoliative 
dermatitis, 65, 1043
Feline tooth resorption , 522–523
Feline (upper) respiratory infections , 
524–525
FeliScratch, 804
Feliway®
for aggression, 50, 54, 57
for fears, phobias, and anxieties, 495
for kitten behavior problems, 804
for urine marking, 658
for veterinary visits, 490
Felty’s syndrome, 1101
FeLV. See Feline leukemia virus
Feminization, male, 67, 679, 680, 1043
Fenbendazole
for canine schistosomiasis, 219
for diarrhea, 22, 214, 509for eosinophilic gastroenteritis, 557
for nasal parasites, 959
for physalopterosis, 1079
Fenoldopam, 24, 708, 992
Fentanyl
for arthrocentesis, 1479
Ferrous gluconate, 86
Ferrous sulfate, 86
Fever , 526–527
shar‐pei. See Shar‐pei fever, familial
of unknown origin (FUO), 526, 527
Fiber, dietary
for clostridial enterotoxicosis, 
284–285
for colitis, 301
for constipation and obstipation, 324
for large bowel diarrhea, 528–529
Fiber‐responsive large bowel diarrhea , 
528–529
Fibrocartilagenous embolic 
myelopathy , 530–531
Fibrosarcoma , 532–534
bone, 532
gingiva, 533
nasal and paranasal sinus, 534
Fibrosing pleuritis, 277
Fibrosis of liver. See Hepatic fibrosis
Filaroides hirthi,  1190–1191
Filgrastim, 1, 928. See also  Granulocyte 
colony‐stimulating factor
Finasteride
for benign prostatic hyperplasia, 168, 
1134
for prostate disease in breeding male 
dog, 1130
for prostatic cysts, 1131
Fine‐needle aspiration , 1525–1526Finnish harrier
Finnish hound, cerebellar degeneration, 
247, 689
Finnish Lapphund, Pompe’s disease, 573
Finnish spitz
FIP . See Feline infectious peritonitis
Fipronil
Fipronil toxicosis , 535
Firocoxib
Fish oils. See Omega‐3 fatty acids
FIV. See Feline immunodeficiency virus
Flank alopecia, canine, 67
Flat‐coated retriever
anemia, 90
eyelash disorders, 482
histiocytic sarcoma, 650, 652
malignant fibrous histiocytoma, 861
synovial cell sarcoma, 1311
Flatulence , 536–537
FLCN  gene mutation, 1042
Flea bite hypersensitivity , 538–539
Flea control , 538–539
Flovent. See Fluticasone
for coccidioidomycosis, 293, 361

1604  Index  
Flucytosine, 345, 361
Fludrocortisone, 720, 721
Fluid analysis , 1527–1529
peritoneal fluid, 1476–1478
pleural fluid, 1550–1552
synovial fluid, 1479–1482
Fluid therapy. See also  T ransfusion therapy
for acute hemorrhagic diarrhea 
syndrome, 555
for acute kidney injury, 23–24
for brain injury, 192–193
hyperglycemic state, 393–394
for diabetic ketoacidosis, 395
for heat stroke/hyperthermia, 
589–590
for hepatic encephalopathy, 612
for hypernatremia, 691
for hyperosmolarity, 692–693
for hyponatremia, 734
for hypovolemic shock, 1243–1244
for lactic acidosis, 806
for myxedema coma, 950
for nephrotic syndrome, 972–973
for nephrotoxicity, 975
for NSAID toxicosis, 981–982
for oliguria and anuria, 992
for peritonitis, 1070for poisoning, 1099
for salt toxicosis, 1219–1220
for septic shock, 1245–1246
for urinary tract obstruction, 1368
Flumazenil, 1450
for benzodiazepine toxicosis, 170
for neonates, 429
Flumethrin toxicosis, 1170
Flunixin meglumine, 16, 527
Fluocinolone, 16, 452, 1056
Fluoroquinones
Fluorosis, dental, 409
5‐Fluorouracil (5‐FU) toxicosis , 1
Fluoxetine
48, 60
495, 497
for feline aggression, 49, 54, 57
1324
Fluralaner
for demodicosis, 66
for tick control, 1339
Flurbiprofen, 99, 101, 742
Fluticasone
for interstitial pneumonia, 1093Focalin. See Dexmethylphenidate
Folate deficiency, 87
Folic acid/folate supplements, 264, 572
Folinic acid (leucovorin), 1347, 1450
Follicular conjunctivitis, 321, 322
Follicular dysplasia, 67, 68, 376
Folliculitis
bacterial. See Bacterial (staphylococcal) 
folliculitis
eosinophilic nasal, of dogs, 957
mural lymphocytic, 66
muzzle, 15
Fomepizole (4‐methylpyrazole), 473, 
475, 1450
Food allergies, 540, 542
Food guarding, aggressive, in dogs , 
51–52
Food intolerance, 540, 542
Food reactions, adverse , 540–543
dermatologic, 540–541
gastrointestinal, 542–543
Food restriction, for obesity, 986–987
Food safety, 1571
Foreign body
acute vomiting, 27
esophageal, 465–466
reactions, cutaneous, 382, 383
Fox terrier. See also  Smooth fox terrier; 
Toy fox terrier; Wirehaired fox 
terrier
Foxhound. See English foxhound
Fragmented medial coronoid process 
(FMCP), 438–439
Francisella tularensis,  1359
French bulldog
1295
cystinuria, 970, 1376
subarachnoid cysts, 1302Fluconazole ( cont’d )

Index  1605
French spaniel, sensory neuropathy, 1107
Fresh frozen plasma
coagulation factor deficiency, 286
for coagulopathy of liver disease, 
288, 289
coagulation, 414
Frostbite, 65
Frustration‐related aggression, in cats, 56
alpha‐L‐Fucosidase deficiency 
(fucosidosis), 769, 1273
Fungal pneumonia , 1090–1091
Fungal rhinitis, chronic, 1199
Fungal urinary tract infection , 840
Furniture, puppies getting on, 1156
for arteriovenous malformation of 
liver, 114
1208
236, 242
for congestive heart failure, 242, 
315–316, 318, 446
for elevated intracranial pressure, 193
cats, 448
for head pressing, 582
for hepatic encephalopathy, 615
for pulmonary edema, 440, 1150for pulmonic stenosis, 1154
for valvular heart disease, 155, 157, 952
Furunculosis
canine eosinophilic nasal, 956, 957
canine muzzle, 15
Fusion teeth, 1342
G
G‐CSF . See Granulocyte colony‐
stimulating factor
for compulsive disorders, 305
for fibrosarcoma, 532, 533
for myelomalacia, 929
for myoclonus, 937
for neuropathic pain, 1276, 1468
for paralysis, 1041
for seizures/status epilepticus, 1226
1334
Gagging , 1268–1269
Galactorrhea, in false pregnancy, 
485–486
Gallbladder. See also  bile duct
agenesis/hypoplasia, 416
cystic mucosal hyperplasia, 544
Gallbladder mucocele (GBM) , 
544–545
bile peritonitis, 177, 178
cholecystitis and choledochitis, 
265–266Gallstones. See Cholelithiasis
Gamma‐aminobutyric acid (GABA) 
antagonist mushroom poisoning, 
916–919
Gamma hydroxybutyric acid (GHB) 
Gammel Dansk Hønsehund, myasthenia 
gravis, 920
Ganciclovir, 322, 502
Gangliosidoses, 930
Garden hazards, toxic, 1452–1464
Gasoline toxicosis, 1074–1075
Gastric adenocarcinoma , 39
Gastric dilation and volvulus 
syndrome (GDV) , 546–547
Gastric lavage, 1098–1099
for chocolate toxicosis, 260
Gastric motility disorders , 548–549
Gastric outflow tract obstruction 
(GOTO), 559–560
Gastric tumors. See Stomach tumors
Gastrinoma, 34, 111
Gastritis, chronic , 550–551
Gastroduodenal ulceration/erosion 
(GUE) , 552–553
melena, 889, 890
Gastroenteritis , 554–557. See also  
Diarrhea
554–555
eosinophilic, 556–557
Salmonella,  1217, 1218
Gastroesophageal reflux (GER) , 558
esophagitis, 469, 470, 471
Gastrointestinal adverse food reactions , 
542–543
Gastrointestinal extramedullary 
plasmacytoma (GI EMP), 1081
Gastrointestinal hemorrhage
1115, 1116
in arteriovenous malformation of the 
liver, 114
in aspirin toxicosis, 126
in NSAID toxicosis, 981
hematemesis, 600–601
melena, 889–890
Gastrointestinal irritant mushroom 
Gastrointestinal obstruction , 559–560
Gastrointestinal stromal tumor (GIST), 
822, 823

1606  Index  
liver, 114
for cirrhosis and fibrosis of the liver, 281
Gator (BAT) sign, 1543, 1544
Gelsemium sempervirens,  1456
Gemcitabine, 31, 34, 1351
Gemfibrozil, 686
Gemination tooth, 1342
Gene therapy
for glycogen storage disease, 573
for lysosomal storage diseases, 859
for mucopolysaccharidoses, 908
for retinal degeneration, 1194
Gentamicin
for acne, 15
Geriatric vestibular disease, in dogs , 
1422–1423
German shepherd
aggression, 46
allergic contact dermatitis, 325
aspergillosis, 122, 442, 1090
cobalamin deficiency, 290compulsive disorders, 306
cone degeneration, 310
cryptococcosis, 344, 360
dental caries, 364
discospondylitis, 411
ear canal tumors, 251
eosinophilia, 450
epilepsy, 454, 1227
exocrine pancreatic insufficiency, 
480, 481
funguria, 840
gastrointestinal obstruction, 559
glomerulonephritis, 566
hemangiosarcoma, 594, 595, 596, 598
hemophilia, 286–287
hip dysplasia, 647
hypoparathyroidism, 736
hypopituitarism, 741
intussusception, 788
ivermectin sensitivity, 792
lumbosacral syndrome, 841, 961
lupus erythematosus, 844, 845
megaesophagus, 883, 1185
mesothelioma, 899
orbital myositis, 1001
panosteitis, 1034
paralysis, 1040paraneoplastic syndromes, 1042
perianal fistula, 300, 1057
phimosis, 1045
pituitary dwarfism, 900
pyoderma, 1162
pythiosis, 1172
renal cystadenocarcinoma, 36, 308
septic arthritis, 118
skin tumors, 578
third eyelid protrusion, 1323, 1324
tricuspid valve dysplasia, 154
uterine tumors, 1387
1393, 1394
ventricular arrhythmias and sudden 
death, 1404, 1409, 1410, 1415, 
1417
German shorthaired pointer
acne, 15
erosive and ulcerative dermatoses, 374
894

Index  1607
vitiligo, 372
von Willebrand disease, 1072, 1327, 
1429
German wirehaired pointer
Gestational diabetes mellitus , 561
Giant cell tumor , 861
Giant kidney worm, 1370, 1371
Giant schnauzer. See also  Schnauzer
arteritis of nasal philtrum, 372, 1401
congenital hypothyroidism, 747
Giardia  spp., 562, 1523, 1524
Giardiasis , 562
Gingival enlargement/hyperplasia , 563
Gingival fibrosarcoma , 533
Gingival squamous cell carcinoma , 
1285
Gingivitis, 1297
Gingivostomatitis, feline chronic 
Ginkgo, 1457
Glanzmann thrombasthenia, 1327
Glargine insulin, 400
Glaucoma , 564–565
congenital, 310, 311
secondary to cataracts, 246
Glide sign, 1544
Gliomas/glial tumors, 129, 194
Glomerulonephritis , 566–567
Glomerulopathy, 308, 309
Glossitis, 519, 1297
Glucagon, 1450
Glucagonoma , 568–569
hepatocutaneous syndrome, 634, 635
Glucocorticoid hepatopathy. See 
Glucocorticoids. See Corticosteroids
Glucophage (metformin) toxicosis , 562
Glucosamine
Glucose curve , 1530–1532
Glucosuria , 570–571
primary renal, 308, 570
Gluten enteropathy in Irish 
setters , 572Gluten sensitivity, 542
Glycogen branching enzyme deficiency, 
573, 948
Glycogen debranching enzyme 
deficiency, 573, 948
Glycogen storage diseases , 573
myopathies, 948
Glycogen‐type vacuolar hepatopathy , 
574–576
Glycopyrrolate
Glycosaminoglycans, polysulfated. See 
Polysulfated glycosaminoglycans
GnRH. See Gonadotropin‐releasing 
hormone
Goiter, 747
Gold salts, 519
Golden angel’s trumpet, 1453
Golden retriever
aggression to children, 46
anemia, 90
dilated cardiomyopathy, 232, 239
distichia, 182
eosinophilic meningoencephalomyelitis,  
442, 896
extraocular/orbital myositis, 938
gingival fibrosarcoma, 533
hemangiosarcoma, 594, 595, 598
hepatocellular carcinoma, 633
histiocytic diseases, 382, 650, 652, 956
Horner’s syndrome, 656
hypothyroidism, 747ichthyosis, 376
laryngeal paralysis, 812
Lyme nephritis, 566, 847
megaesophagus, 883
pigmentary uveitis, 100
seasonal nasal hypopigmentation, 
372, 956
thymoma, 1335
Gonadotropin‐releasing hormone (GnRH)
for breeding, 197
for cryptorchidism, 346
for ovarian remnant syndrome, 1018
for testicular degeneration and 
hypoplasia, 1319
for vaginal hyperplasia and prolapse, 
1393
Gonadotropins. See also  Human 
Gordon setter
cerebellar degeneration/ataxia, 130, 
247, 689
Gorilla Glue®, 408

1608  Index  
Gracilis muscle contracture, 914, 915
Granulocyte colony‐stimulating factor 
(G‐CSF). See also  Filgrastim
deficiency, 978
Granuloma
canine leproid, 922, 923
collie. See Collie granuloma
eosinophilic. See Eosinophilic 
granuloma
idiopathic sterile, 382, 383
sperm, 1272
Spirocerca lupi,  467
Granulomatous colitis (GC), 300, 
301, 303
Granulomatous dermatoses , 382–383
Granulomatous hepatitis , 626–627
Granulomatous 
meningoencephalomyelitis 
(GME), 584, 897
Granulomatous sebaceous adenitis . See 
Sebaceous adenitis, 
granulomatous
Grape toxicosis , 577
Grapefruit seed extract, 1457
Grapeseed extract, 1389
Grapiprant
for pain management, 1022, 1467
Grass awns, 17, 411, 1009, 1094, 1169
Gray collie
blood smears, 1494
bone marrow aspirates, 1505
hepatic amyloid, 609
Great Dane
acne, 15
anterior uveitis, 100
252, 961
compulsive disorders, 306craniomandibular osteopathy, 341
Great Pyrenees (Pyrenean mountain dog)
laryngeal paralysis‐polyneuropathy 
complex, 812, 1107, 1295
thrombasthenia, 1327
Greater Swiss mountain dog, 
Green‐lipped mussel extract, 1472
Greyhound. See also  Italian greyhound
bone marrow aspirate and biopsy, 
1502
erosive polyarthritis (EPG), 1101, 
1482
erythrocytosis, 462
meningoencephalitis, 442myoglobinuria, 604
thrombocytopenia, 1327
thyroid hormone levels, 748
Grief counseling, 1572
Griffon Briquet, spinal muscular atrophy, 
1107
Griseofulvin, 283, 371, 507
Growth factors, hematopoietic. See 
Hematopoietic growth factors, 
recombinant
Growth hormone (GH)
anomalies, bone disorders, 900–901
for dwarfism, 901
excess, feline acromegaly, 700
Guafenesin, 340
Gyromitrin poisoning, 916
H
H1‐receptor antagonists. See 
H2‐receptor antagonists
in apudomas, 111
114
225
in gastric motility disorders, 549
553, 890
in megaesophagus, 884
in syringomyelia, 1313
in vomiting, 1427
Hair follicle dystrophy, 65
Hair follicle tumors , 578
Halitosis , 579–580
Hallucinogenic mushroom poisoning, 
916–919
Handling, fearful and anxious patients, 
490–491, 492–493

Index  1609
HAS2  gene mutation, 74
Havana brown cat, cerebellar 
abiotrophy, 247
Havanese
granulomatous sebaceous 
adenitis, 1224
sebaceous adenitis, 67
Haw’s syndrome, 1325, 1326
hCG. See Human chorionic 
gonadotropin
Head pressing , 581–582
Head tilt , 583–584
Head trauma, 192–193
Head tremors (bobbing), idiopathic, in 
dogs , 585, 1355
Heart, tumors of. See Cardiac tumors
Heart block. See Atrioventricular block
Heart failure, congestive. See Congestive 
heart failure
Heart murmurs , 912–913
Heart rate, 1447
Heartguard, for baylisascariasis, 167
Heartworm disease (dirofilariasis) , 
586–588
in cats, 586
in dogs, 587–588
Heat stroke , 589–590
Hedera helix,  1453
Heinz body anemia , 83
Helicobacter  spp. , 591–592
Helleborus niger,  1453
Hemangioma, 384
Hemangiopericytoma , 593
Hemangiosarcoma , 594–599
bone, 594
heart, 595
pericardial effusion, 1058, 1059, 1060
skin, 384, 596–597
spleen and liver, 598–599
Hematemesis , 600–601
Hematochezia , 420–421
Hematologic tests
reference ranges, 1441
unit conversion table, 1442
recombinant. See also  
Granulocyte colony‐stimulating 
factor
Hematuria , 602–603
Hemeralopia, 1193
Hemerocallis  ingestion, 834
Hemifacial spasm, 483Hemivertebra, 313
Hemoabdomen, 1477
Hemodialysis, for acute kidney injury, 24
Hemoglobinuria , 604–605
Hemolytic anemia, 90–91
immune‐mediated (IMHA), 84–85, 
87, 90–91
in phosphofructokinase deficiency, 
1078
Hemolytic transfusion reactions, 186
Hemophagocytic histiocytic sarcoma 
(HHS), 90, 650, 651
Hemophilia, 286–287, 460
Hemorrhagic effusions, 1527, 1528, 1529
Hemorrhagic stroke, 249–250
Hemothorax , 606
Hemotropic mycoplasmosis , 607–608
Heparin. See also  Low molecular weight 
heparin
coagulation, 288, 414
for infectious (viral) canine 
hepatitis, 628
1152
Hepatic abscess , 630–631
Hepatic amyloid , 609–610
Hepatic disease. See Liver disease
Hepatic encephalopathy (HE) , 
611–613
1115, 1116
liver, 113
in cirrhosis and fibrosis of the liver, 280
1118
Hepatic failure, acute , 614–616
Hepatic fibrosis , 279–281
congenital (CHF), 279, 416–418
Hepatic lipidosis (feline) , 617–619
syndrome, 262, 263, 264
Hepatic nodular hyperplasia (HNH) , 
620–621
Hepatitis , 622–631
chronic, 622–625
granulomatous, 626–627
infectious (viral) canine, 628–629
suppurative, 630–631Hepatocellular adenoma , 632
Hepatocellular carcinoma , 633
Hepatocellular dysplastic hyperplasia 
(HDH) , 620–621
Hepatocutaneous syndrome , 634–635
Hepatomegaly , 636–638
Hepatoportal microvascular dysplasia 
(MVD) , 639–641
for acute hepatic failure, 616
Hepatosupportive therapies , 642
Hepatotoxins , 643–644
Hepatozoon americanum,  645, 1338, 
1339
Hepatozoon canis,  645, 1338, 1339
Hepatozoonosis , 645
tick vectors, 1338, 1339
Herbal toxicities, 1457–1459
Hermaphrodite, true, 1238
Hernia
diaphragmatic, 401
hiatal, 646
perineal, 1061–1062
peritoneopericardial diaphragmatic, 
1068
Heroin toxicosis, 996–997
Herpesvirus infection, canine ,  
964–965. See also  Feline 
herpesvirus infection
Hetastarch. See Hydroxyethyl starch
Heterobilharzia americana,  219,  
836, 837
Heterobilharziasis , 219
Hiatal hernia , 646
High altitude, 750
High anion gap acidosis, 12–13
High‐dose insulin euglycemia (HIE)
Hill’s Prescription Diet® b/d, 295
Hill’s Prescription Diet® c/d Multicare, 
505
Hill’s Prescription Diet® Canine s/d, 
1381, 1382
Hill’s Prescription Diet® Canine u/d, 
1373, 1376
Hill’s Prescription Diet® Canine w/d, 
1373
Hill’s Prescription Diet® Feline s/d, 1379
Hill’s Prescription Diet® Feline w/d, 1373
Hill’s Prescription Diet® Multicare Feline 
Urinary Stress, 55

1610  Index  
Himalayan cat
1115
dermatophytosis, 370
ductal plate malformation, 262
eyelid disorders, 182
housesoiling, 657
polycystic kidney disease, 308, 1105
skin tumors, 165, 378
Hip dysplasia , 647–649
Hippuric acid crystals, urinary, 349
Histamine H1 antagonists. See 
Histamine H2 antagonists. See H2‐
receptor antagonists
Histiocytic diseases—dogs and cats , 
650–651
Histiocytic sarcoma (HS), 650, 651
cutaneous, 652
disseminated (malignant 
histiocytosis), 382
hemophagocytic (HHS), 90, 650, 651
Histiocytic ulcerative colitis , 303
Histiocytoma, 652
cutaneous, 378, 650, 651
malignant fibrous, 861
Histiocytosis, cutaneous (CH) , 652
Histoplasmosis , 653–654
Holly, English, 1453
Home hazards, toxic, 1452–1464
Hookworms , 655
Hordeolum, 182
Hormones
assay unit conversion table, 1446
testing protocols, 1444–1445
Horner’s syndrome , 656
Horse chestnut, 1454
Household cleaners, toxicities, 1460–1464
Housesoiling , 657–662
Housetraining, dogs, 661–662, 1156Human chorionic gonadotropin (hCG)
1393
Human‐directed aggression
in cats, 49–50, 56
in dogs, 44–48, 58
Humectants, for exfoliative 
Humulin N, 400
Huntaway dog, mucopolysaccharidosis, 
908
Hunting dog hypoglycemia, 727, 728
Hurricane plant, 1455
Husky. See also  Siberian husky
cough, 339
Hyacinth ( Hyacinthus  spp.), 1456
Hyaluronic acid, for osteoarthritis, 116
Hydralazine
for canine pregnancy edema, 1123
for congestive heart failure, 316, 446
for hypertension, 707–708
Hydrocarbon toxicosis, 1074–1075
Hydrocephalus , 663–664
Hydrochlorothiazide
for ascites, 121
for dilated cardiomyopathy, 233
disease, 953
for urolithiasis, 1373
Hydrocodone
Hydrocortisone
Hydrofluoric acid (HF) exposure, 1461
Hydrogen peroxide
for antidepressant toxicosis, 104–105for chocolate toxicosis, 261
for dermatophytosis, 370
Hydrolyzed protein diets, 542
Hydromorphone
Hydronephrosis , 665–666
Hydrotherapy, for hip dysplasia, 648
Hydroxychloroquine, for discoid lupus 
erythematosus, 844
Hydroxycobalamin, 89, 290, 1450
Hydroxyethyl starch (hetastarch)
for hypoalbuminemia, 722
hypertonic, for glaucoma, 565
thrombocytopathic effect, 1327
5‐Hydroxytryptophan, 1458
Hydroxyurea
for erythrocytosis, 463
for polycythemia vera, 1106
for thrombocytosis, 1333–1334
Hydroxyzine, 16
Hyoscyamine
Hyperadrenocorticism (HAC) 
(Cushing’s syndrome) ,  
667–671
in cats, 667
in dogs, 668–671
endocrine function testing, 1444
feline skin fragility syndrome, 1261
glycogen‐type vacuolar hepatopathy, 
574, 575
myopathy, 941, 942
Hyperandrogenism
alopecia, 69, 70
disorders of sexual development,  
1238
Hyperbaric oxygen therapy, 223, 1275

Index  1611
Hyperbilirubinemia
extrahepatic bile duct obstruction 
(EHBDO), 174–176
icterus, 752–753
tooth discoloration, 409
Hypercalcemia , 672–673
in anal sac adenocarcinoma, 29, 30
1209, 1210
in thyroid adenocarcinoma, 40
Hypercalciuria, 1372
Hypercapnia , 674–675, 1485
Hyperchloremia , 676
Hyperchloremic metabolic acidosis, 12, 
13, 676, 1187
Hypercholesterolemia, 267, 685
Hyperchylomicronemia, in cats, 685, 
686, 1108
Hypercoagulability , 677
Hypereosinophilic syndrome 
(HES) , 678
Hyperesthesia syndrome, feline. 
See Feline hyperesthesia 
syndrome
Hyperestrogenism (estrogen toxicity) , 
679–680
alopecia, 67, 69, 70
in Sertoli cell tumor, 1237
Hyperglycemia , 681–682
hyperosmolar hyperglycemic 
state, 393
Hyperkalemia , 683–684
in azotemia and uremia, 159
in hydronephrosis, 666
in urinary tract obstruction, 
1368–1369
Hyperlactatemia , 805–807
Hyperlaxity syndrome, 793
Hyperlipidemia , 685–686
cholelithiasis, 267, 268
dietary prevention of urolithiasis, 
1374
lipid flare, 742
Hyperlipoproteinemia, corneal 
opacities, 336
Hypermagnesemia , 687–688
Hypermetria , 689–690
Hypernatremia , 691
in salt toxicosis, 1219–1220
Hyperosmolar hyperglycemic state, 
diabetes mellitus , 393–394
Hyperosmolarity , 692–693
Hyperoxaluria, 308, 309, 1372Hyperparathyroidism , 694–697
hypercalcemia, 672
renal secondary, 696–697
Hyperphosphatemia , 698–699
Hypersensitivity vasculitis, 350
Hypersomatotropism/acromegaly in 
cats, 700
Hypertension , 701–708
in canine pregnancy edema, 1123
measurement, 1488–1489
in pheochromocytoma, 1076, 1077
portal, 701–703
pulmonary, 704–705
systemic arterial, 706–708
Hypertensive emergency, 707–708
Hypertensive retinopathy, 1195, 1196, 
1197
Hyperthermia , 589–590
in brachycephalic airway syndrome, 
191
Hyperthyroidism , 709–710
alopecia, 66
thyroid adenocarcinoma, 40, 41
Hypertonic saline
Hypertrophic cardiomyopathy (HCM) , 
235–238
aortic thromboembolism (ATE), 108, 
in cats, 235–237
in dogs, 238
systolic anterior motion, 1315
Hypertrophic osteodystrophy , 
711–712
Hypertrophic osteopathy , 713, 1043
Hypertrophic pyloric gastropathy, 
chronic , 714–715
Hyperuricuria, 308
Hyperventilation, therapeutic, 193, 
1301, 1485
Hyperviscosity syndrome (HVS) , 716
paraproteinemia, 1046
Hyphema , 717–718
Hypoadrenocorticism , 719–721
atrial standstill, 142
Hypoalbuminemia , 722–723
in nephrotic syndrome, 972–973
in protein‐losing enteropathy, 1136Hypoalbuminemic alkalosis, 63–64
Hypocalcemia , 724–725
in dystocia, 429
in hypoparathyroidism, 724, 725, 
736–737
postoperative, 41
postparturient (eclampsia), 433
Hypochloremia , 726
Hypochloremic alkalosis, 63, 64
Hypochondrodysplasia, 1006
Hypocitraturia, 1372
Hypoglycemia , 727–728
in ethanol toxicosis, 473
in insulinoma, 776, 777
paraneoplastic, 1044
Hypokalemia , 729–730
in beta‐2 agonist inhaler toxicosis, 172
metabolic alkalosis, 63, 64
Hypoluteoidism, 2, 3, 4
Hypomagnesemia , 731–732
Hypomyelination , 733
Hyponatremia , 734–735
Hypoparathyroidism , 736–738
Hypophosphatemia , 739–740
anemia, 90
in hepatic lipidosis, 618
Hypopituitarism , 741
Hypoproteinemia, 121
Hypopyon , 742
Hyporexia , 743
Hyposensitization, for atopic 
dermatitis, 134
Hyposomatotropism, congenital, 741
Hypospadias, isolated, 1238
Hyposthenuria , 744
Hypotension, measurement, 1488–1489
Hypothermia , 745–746
in neonates, 965, 966
Hypothyroidism , 747–749
alopecia, 65, 67, 68
congenital, 747
familial lymphocytic, 4
head tilt, 584
infertility, 767, 768, 769
myxedema and myxedema coma, 950
Hypotrichosis, congenital
canine, 67
feline, 65
Hypoventilation, 674, 750, 1485
Hypovitaminosis D, 694, 724
Hypovolemic shock , 1243–1244
Hypoxemia , 750–751

1612  Index  
I
Ibuprofen toxicosis, 981
Ichthyosis, 376
Icterus , 752–753
Idiopathic pulmonary fibrosis (IPF), 
1092–1093
Idioventricular rhythm , 754–755
Idoxuridine, 320, 322, 502
Ileus , 756–757
Ilex spp., 1453
Illicit/club drug toxicosis , 758
Imatinib mesylate, 678, 705
Imepitoin, 1323
Imerslund‐Gräsbeck syndrome. See 
Cobalamin (vitamin B12), 
congenital malabsorption
Imidacloprid, 539, 655, 968, 1212
Imidacloprid/moxidectin, 257, 432, 983
Imidazoline toxicosis , 759
Imidazopyridine toxicosis, 169–170
Imidocarb dipropionate
for babesiosis, 161, 162, 460
Imipenem, 76
Imipramine, 766, 954
Imiprothrin toxicosis, 1170
Imiquimod
for multicentric squamous cell 
carcinoma in situ,  1288, 1289
for papillomatosis, 1039
for squamous cell carcinoma, 1284
Immune complex disorders, 
Immune complex glomerulonephritis 
(ICGN), 566, 567, 847, 848
Immune‐mediated anemia , 84–85
Immune‐mediated hemolytic anemia 
(IMHA), 84–85, 87, 90–91
Immune‐mediated polyarthritis, in dogs, 
1103–1104
Immune‐mediated thrombocytopenia, 
primary , 1329–1331
Immunodeficiency disorders, primary , 
760–761
Immunoglobulin, intravenous. See 
Intravenous immunoglobulin
Immunoglobulin A (IgA) deficiency, 
760, 761
Immunoglobulin M (IgM) deficiency, 
760
Immunoproliferative enteropathy of 
Basenjis , 762
Immunosuppressive drugs
for cold agglutinin disease, 297
for glomerulonephritis, 567for immune‐mediated anemia, 85
for retinal detachment, 1196
for atopic dermatitis, 134
for feline asthma, 128
Imodium. See Loperamide
Impaired veterinarians and veterinary 
technicians, 1571
Impetigo, 1163
Impression smear , 1533
Impulse control aggression, in cats, 56
Inca hairless, 67
Incilius alvarius,  1340
Incontinence , 763–766
fecal, 763–764
urinary, 765–766
Independence training, for separation 
anxiety syndrome, 1232
Indian common mallow, 1459
Indolent ulcer, feline, 451
Indoxacarb, 539
Infectious (viral) canine hepatitis , 
628–629
Infective endocarditis , 445–446
Infertility , 767–770
in female dogs, 767–768
in male dogs, 769–770
Inflammatory bowel disease (IBD) , 
771–772
chronic diarrhea, 404, 406
chronic gastritis, 550, 551
colitis and proctitis, 301
eosinophilic gastroenteritis, 556, 557
Inflammatory myopathy
focal, 939–940
generalized, 940–941
Influenza , 773–774
Infraspinatus muscle contracture, 914, 
915, 1247, 1248, 1249
Infundibular keratinizing 
acanthoma, 578
Injection site alopecia, 67
Injection site sarcoma, feline (FISS), 
1270, 1271
Inotropes, positive
for hypovolemic shock, 1244for septic shock, 1246
Insect development inhibitors 
(IDIs), 539
Insect growth regulators (IGR), 539
Insecticides
for flea control, 538–539
for leishmaniosis control, 826
neonicotinoid toxicosis, 968
organophosphate and carbamate 
toxicosis, 1003–1004
pyrethrin and pyrethroid toxicosis, 
1170
for tick control, 1337, 1339
Insemination, timing, 196–197
Insoluble oxalate plant toxicosis , 775
Insulin
for diabetes mellitus, 397–398, 400
for diabetic ketoacidosis, 395–396
for hyperglycemia, 682
serum, 1445
Insulinoma , 776–778
Intercat aggression , 53–55, 56
Interferons
Intermale aggression, in cats, 53
Interstitial cell tumor, testicle , 779
Interstitial pneumonia , 1092–1093
Intervertebral disc disease , 780–787
in cats, 780
cervical, 781–783
neck and back pain, 961, 962
spinal cord myelomalacia, 929
thoracolumbar, 784–787
Intestinal leiomyositis, lymphocytic, 
756, 757
Intestinal obstruction, 559–560
Intestinal pseudo‐obstruction,  
756–757

Index  1613
Intoxication
antidotes and useful drugs, 
1449–1451
garden plants, 1452–1456
herbal preparations, 1457–1459
home and garden hazards, 1452–1464
household cleaners, disinfectants, and 
solvents, 1460–1464
resources, 1572
Intoxication (poisoning) therapy , 
1098–1099
Intracranial pressure (ICP), elevated
in brain injury, 192, 193
in stupor and coma, 1301
Intralipid. See Intravenous lipid 
emulsion
Intraocular pressure (IOP), 564, 565, 
1509, 1511
Intravenous fluids. See Fluid therapy
Intravenous immunoglobulin (IVIG), 
85, 327, 1332
Intravenous lipid emulsion, 1099
171
1208
1306
for tricyclic antidepressant 
toxicosis, 105
Intussusception , 788–789
Iodine‐131 (radioiodine) therapy, 40, 
41, 710
Ipodate (iopanoic acid), 710
Ipomoea purpurea and tricolor,  1455
Iridocyclitis, 98, 100
Iris atrophy , 790
Iris cysts, 310
Iris hypoplasia, 92
Iris melanoma. See Uveal melanoma
Iris plant ( Iris spp.), 1454
Irish ivy, 1453
Irish potato, 1454
Irish setter
anemia, 90
cerebellar disease, 247, 248, 689
color dilution alopecia, 67
epilepsy, 454exfoliative dermatoses, 376
gluten‐sensitive enteropathy,  
542, 572
perianal fistula, 1057
skin tumors, 378, 578, 888
1318
Irish terrier, cystinuria, 1376
Irish water spaniel, myocardial tumors, 
934
Irish wolfhound
Fanconi syndrome, 489
Iritis, 98, 100
Iron‐deficiency anemia , 86, 87, 88
Iron dextran, 80, 86, 680
Iron therapy, 86
Iron toxicosis , 791
Irritant contact dermatitis, 325
Ischemic dermatopathy 
(dermatomyositis‐like),  
367–368
Ischemic encephalopathy, feline (FIE) , 
512–513
Ischemic stroke, 249, 250
Isoerythrolysis, neonatal, 964
Isoniazid, 923, 1451
Isopropanol toxicosis, 473, 1464
Isoproterenol
for atrioventricular block, 147, 153
for sinus bradycardia, 1257Isosorbide dinitrate, 953
Isotretinoin. See also  Retinoids
for acne, 14, 381
for cutaneous epitheliotropic 
lymphoma, 858
for pilomatricoma, 578
for thyroid adenocarcinoma, 40, 41
Italian greyhound
Italian spinone
Itch. See Pruritus
for blastomycosis, 180–181, 361
for cuterebriasis, 351, 444
for demodicosis, 362
for ear mites, 432
513
for nasal parasites, 959, 1200, 1269
sensitive dog breeds, 257, 363, 1221
Ivermectin toxicosis , 792
Ivy, 1453

1614  Index  
Ixodes  ticks, 1338
anaplasmosis, 436
tick paralysis, 1336, 1337
J
Jack Russell terrier. See also  Parson Jack 
Russell terrier
cerebellar abiotrophy, 248
cough, 339
maternal behavior problems, 877
neuromyotonia and myokymia, 945
vasculitis, 1401
JAK2  gene mutation, 1106
Japanese bobtail cat, blood type, 1499
Japanese spaniel
Jaundice (icterus) , 752–753
Jaw fractures , 879–880
Jerusalem cherry, 1454
Jimsonweed, 1456
Jindo, pseudohyperkalemia, 683
Joint luxations , 793–794
Jonquil, 1455
Jumping behavior, dogs , 1361–1362
Juvenile cellulitis (puppy strangles) , 
1159
Juvenile polyarteritis in beagles, 74, 1401
Juvenile vaginitis, 1397, 1398
K
Kalanchoe  spp., 1452
Kalmia  spp., 1455
Karelian bear dog, hypopituitarism, 741
KCNJ10  gene, 907, 945
KCNQ1  gene, 1415
Keeshond
alopecia, 67, 68, 69
copper associated hepatopathy, 328
hyperparathyroidism, 672, 694
hypophosphatemia, 739
renal dysplasia, 308skin tumors, 578
Kelpie, dermatomyositis, 367
Kennel cough. See Canine infectious 
respiratory disease
Keppra. See Levetiracetam
Keratitis , 795–799
chronic superficial, 796, 797
exposure, 798
feline eosinophilic, 795, 796, 797
nigrum. See Corneal sequestrum
nonulcerative, 796–797
pigmentary, 796, 797
ulcerative, 798–799
Keratoconjunctivitis sicca (KCS) , 800
in Sjögren‐like syndrome, 1260
ulcerative keratitis, 798, 799
Keratoconjunctivitis sicca ichthyosiform 
dermatosis (KCSID), 310
Kerry blue terrier
cerebellar disease, 130, 247, 248, 
689, 907
Ketamine
pain (acute, chronic, and 
Ketoacidosis, diabetes mellitus with , 
395–396
282–283
for hyperadrenocorticism, 670
Ketoprofen
for osteoarthritis, 1470, 1471
Ketorolac, 99, 101, 742
Ketotifen, 322
Key‐Gaskell syndrome. See 
Dysautonomia
Kidney disease
acute. See Acute kidney injury
amyloidosis, 74–75, 308
anemia, 80–81, 87, 88
azotemia and uremia, 159–160chronic. See Chronic kidney disease
308–309
cylindruria, 355
glomerulonephritis, 566–567
proteinuria, 1138–1140
Kidney stones (nephrolithiasis) , 
970–971
Kinostat, 246
Kirby‐Bauer disc diffusion, 1483, 1484
c‐Kit mutations, 822, 823, 874
Kitten behavior problems , 801–802
Kitten socialization and kitten classes , 
803–804
Klee kai, cyanosis, 352
Klinefelter syndrome, 1238
Klonopin. See Clonazepam
Komondorok
cobalamin malabsorption, 87, 89
Korat cat, lysosomal storage disease, 859, 
930, 1107
Kuvasz
L
La Perm cat, pyruvate kinase deficiency, 
1171
Labial mucositis, 1297
Laboratory tests, reference ranges, 
1441–1443
Labradoodle, cone degeneration, 310
Labrador retriever
arteriovenous malformations, 112
bile duct carcinoma, 173
cerebellar disease, 130, 247, 248
chondrosarcoma, 270
copper associated hepatopathy/chronic 
hepatitis, 279, 328, 329, 622
cough, 339
cruciate ligament disease, 342
dysphagia, 424

Index  1615
478–479
histiocytic diseases, 378, 382, 650, 652
lipoma, 378, 835
lymphedema, 853, 1065
mast cell tumors, 378, 874
myopathy (hereditary), 943
nasal parakeratosis, 956
oculo‐skeletal dysplasia, 310
salmon poisoning disease, 1216
372, 956
seborrhea (primary idiopathic), 385septic arthritis, 118
squamous cell carcinoma, 1288
tricuspid valve disease, 154, 156
uveal melanoma, 1389
1393, 1394
Labrador retriever exercise‐induced 
weakness/collapse , 478–479
Labrador retriever myopathy, 
hereditary , 943
Lacrimal system anomalies, congenital, 
310
Lactic acidosis , 805–807
Lactitol, 612–613
Lactoferrin, 519
Lactose, 612–613
Lactose intolerance, 536
Lactulose
for bowel preparation, 176
for hepatic amyloid, 610
612–613, 615
for perineal hernia, 1062
Lagophthalmos, 798
Lagotto‐Romangolos, hereditary ataxia, 
689–690
Lakeland terrier
Lambda cyhalothrin toxicosis, 1170
Lameness , 808–809
Landseer
Langerhans cell histiocytosis, 650, 651, 652
Lanreotide, 777
Lantana (Lantana camara),  1454
Lanthanum carbonate, 696, 699
Lapland dog, glycogen storage disease, 
573, 948
Lapphund, glycogen storage disease, 573
Large bowel diarrhea, fiber‐responsive , 
528–529
Large intestinal tumors
leiomyoma, 822
leiomyosarcoma, 823Larkspur, 1453
Laryngeal diseases , 812–813
Laryngeal paralysis, 812, 813
polyneuropathy complex, 424, 812
stertor and stridor, 1295, 1296
Laryngeal perforation , 810–811
Laser therapy, for postoperative pain, 1023
Lasix. See Furosemide
Latanoprost, 565, 827
Latrodectus  antivenoms, 1274
Latrodectus  spider venom toxicosis, 1274
Lavender essential oils, 221
Laxatives, 324, 420, 882
Lead toxicosis , 814–815
antidote, 1450
nonregenerative anemia, 87, 88
Leflunomide
Left anterior fascicular block , 816–817
Left bundle branch block , 818–819
Left ventricular outflow tract obstruction 
(LVOTO), 155, 238, 1315
Legg–Calvé–Perthes disease , 820–821
Leiomyoma, stomach, small and large 
intestine , 822
Leiomyosarcoma, stomach, small and 
large intestine , 823
Leiomyositis, intestinal lymphocytic, 
756, 757
Leishmania infantum (L. chagasi),  824, 
825–826, 1093
Leishmaniosis , 824
cutaneous, 825–826
Lens‐induced uveitis, 246
Lens luxation , 827
Lenticular nuclear sclerosis, 245, 246
Leonberger
Leproid granuloma, canine, 922, 923
Leprosy, feline, 922, 923
Leptospirosis , 828–829
Leucine crystals, urinary, 349
Leucovorin (folinic acid), 1347, 1450
Leukemia . See also  Feline leukemia virus 
(FeLV) infection
chronic lymphocytic, 830
chronic myelogenous, 932
Leukeran. See Chlorambucil
Leukocyte adhesion deficiency, 831
Leukocytosis , 831–832

1616  Index  
Leukoderma, 372
Leukoencephalitis, necrotizing 
(NLE), 963
Leukoencephalomyelopathy in 
Rottweilers , 833
Leukotrichia, 372
Levabuterol toxicosis, 172
Levamisole, 846, 1093, 1191
1228
Levobunalol, 565
Levothyroxine (L‐thyroxine)
for hypothyroidism, 749
Lhasa apso
eyelid abnormalities, 182
head pressing, 581
urolithiasis/crystalluria, 348, 1372
LHX3  gene mutations, 741
Lidocaine
172
for chocolate toxicosis, 261for cholecalciferol rodenticide 
for myocardial tumors, 934
for pain management, 1466
for ventricular arrhythmias, 1404, 
1406, 1417
Lily of the valley, 1454
Lily toxicosis , 834
Lime‐sulfur solutions
for demodicosis, 66, 363
D‐Limonene, 472
Lincomycin, 876
Linear immunoglobulin A (IgA) 
dermatosis, 385, 386
Lingual squamous cell carcinoma , 
1290
Linguatula serrata,  1190–1191
Linoleic acid, 858
Linseed oil toxicosis, 1074–1075
Liothyronine, 749
Lipid emulsion therapy. See Intravenous 
lipid emulsion
Lipid flare (ocular) , 742
Lipid pneumonia, 1092, 1093
Lipid storage myopathies, 948–949
Lipoma
cutaneous, 378
infiltrative, 835
Lisinopril, 233
Lithium ion battery toxicosis, 166
Litter boxes, cat
appropriate provision, 658, 870
elimination outside of, 53, 54, 
657–660
hygiene, 1347
Liver
amyloidosis, 609–610
arteriovenous malformation, 113–114
cirrhosis and fibrosis, 279–281
Liver disease
anemia, 87, 88
ascites, 121
coagulopathy of, 288–289
supportive therapies, 642
Liver fluke infestation , 836–837Liver tumors
hemangiosarcoma, 598–599
hepatocellular adenoma, 632
Local anesthetics, 1466 See also  lidocaine, 
bupivacaine
Lokivetmab, 135, 1143
Lomustine (CCNU)
for astrocytoma, 129
for lymphoma, 857, 858
Long‐haired dachshund, sensory 
neuropathy, 1107
Long‐haired miniature dachshund
Long‐haired whippet, ivermectin 
sensitivity, 792
Loperamide
toxicosis, 996
Lorazepam
for feline aggression, 55, 57
for mounting behavior, 871
1334
Losartan, 281
Low molecular weight heparin (LMWH)
1152
Lower motor neuron (LMN) lesions, 
1040, 1107
Lower urinary tract disease, feline 
idiopathic , 504–505
Lower urinary tract infection , 838–840
bacterial, 838–839
fungal, 840
Loxosceles  spider venom toxicosis, 1275
Lufenuron, 167, 371, 539
Lumbosacral stenosis , 841–842
Lundehund. See Norwegian Lundehund
Lung and pleural space point-of-care 
ultrasonography , 1541–1546

Index  1617
Lung consolidation, 1546
Lung‐digit syndrome, 31
Lung lobe torsion , 843
Lung tumors
adenocarcinoma, 31
squamous cell carcinoma, 1286
Lungworms, 1190–1191
Lupin ( Lupinus  spp.), 1454
Lupus erythematosus , 844–846
cutaneous. See Discoid lupus 
erythematosus
systemic. See Systemic lupus 
Lurcher, hypomyelination, 733
Lutalyse. See Prostaglandin F2αLuxations, joint , 793–794
Lyme borreliosis , 847–848
associated glomerulonephritis, 566
tick vectors, 847, 1338
vaccines, 848, 1339
Lymphadenitis , 851–852
Lymphadenopathy , 851–852
Lymphangiectasia , 849–850
Lymphedema , 853, 1066
primary/congenital, 853, 1065
Lymphocytic hypothyroidism,  
familial, 4
Lymphocytic leiomyositis, intestinal, 
756, 757
Lymphocytic mural folliculitis, 66
Lymphocytic orchitis, 769
Lymphocytic/plasmacytic conjunctivitis, 
321, 322
Lymphocytic thyroiditis, 747, 749
Lymphocytosis, 831
Lymphoid hyperplasia/reactivity, 
851, 852
Lymphoma , 854–858
brain, 195
in cats, 854–855
cutaneous epitheliotropic. See 
lymphoma
in dogs, 856–857
in feline leukemia virus infection, 514, 
515, 854, 855
heart, 1060
lymphadenopathy, 851, 852
Lymphosarcoma. See Lymphoma
Lyovac antivenin, 1274
Lyrica. See Pregabalin
Lysergic acid diethylamide (LSD) 
Lysine (L‐lysine)
799
for viral dermatoses, 387Lysine‐lactoferrin, for feline herpesvirus 
infection, 502
Lysosomal storage diseases , 859
M
Ma huang, 1144, 1458
Macrocyclic lactone toxicosis , 792
Macrodontia, 1342
Macrolide antibiotics. See also  
Azithromycin; Clarithromycin; 
Macrothrombocytopenia, inherited , 
1145
Magnesium ammonium phosphate 
(MAP). See Struvite
Magnesium chloride, 396, 732, 1406
Magnesium hydroxide (milk of 
magnesia), 191, 791
Magnesium sulfate
for hypomagnesemia, 732
for ventricular fibrillation, 1406
Maine coon cat
hypertrophic cardiomyopathy, 
235, 1315
spinal muscular atrophy, 930, 1107
Maintenance energy requirements 
(MER), 986, 1432
Malamute. See Alaskan malamute
Malassezia  dermatitis , 860
Malignant fibrous histiocytoma , 861
Malignant hyperthermia, 589
Malignant peripheral nerve sheath 
tumors (MPNST), 976, 1223
Malinois. See Belgian Malinois
Malocclusions, skeletal and dental , 
862–863
Maltese
cirrhosis and fibrosis of liver, 279
encephalitis, 442, 581, 963
gastroenteritis, 554
639, 640hydrocephalus, 663
persistent deciduous teeth, 359
seizures, 1227
shaker/tremor syndrome, 1240
thrombocytopenia, 1072, 1329
Mammary gland hyperplasia, in cats , 864
Mammary gland tumors , 865–868
in cats, 865–866
in dogs, 867–868
Manchester terrier
Mandibular fractures , 879–880
Mannitol
1208
for hepatic encephalopathy, 613, 615
Manx cat
constipation and obstipation, 323
megacolon, 881
rectal and anal prolapse, 1180
sacrococcygeal dysgenesis, 313
spinal dysraphism, 1276, 1277

1618  Index  
Marbofloxacin
for mycoplasmosis, 607
Marijuana toxicosis , 869
Marine (cane) toad intoxication, 1340
Marking behavior , 870–873
in cats, 870–871
in dogs, 872–873
for esophagitis, 471
553
Mass or organ aspiration, ultrasound‐
guided , 1555–1558Mast cell tumors , 874–875
cutaneous, 378, 874–875
Masticatory muscle myositis , 938–939
Mastiff. See also  Bullmastiff; Tibetan 
mastiff
acne, 15
cystinuria, 1376, 1568
retinal degeneration, 1193, 1195
1393, 1394
Mastitis , 876
Maternal aggression, in cats, 49, 53, 56, 
877, 878
Maternal behavior problems , 877–878
Maxillary fractures , 879–880
MC4R  gene mutations, 986
MDR1/ABCB1  gene mutations, 225, 
257, 792, 996, 1014, 1269
Mechlorethamine, 858
Meclizine
Medial compartment disease of elbow, 
438, 439
Medial coronoid process disease, 438, 439
Medial shoulder instability, 1247, 1248, 
1249
Medium‐chain triglycerides (MCTs), 
296, 850
Medroxyprogesterone acetate, 70, 741, 
1134
Megacolon , 881–882
Megaesophagus , 883–885
regurgitation, 1185, 1186
in vascular ring anomalies, 1399
Megaloblastic anemia , 89
Megestrol acetate
for subinvolution of placental sites, 
1304
Meglumine antimonite, 824, 826, 1093
Melanocytic tumors/melanoma , 
886–888
DNA vaccine, 887, 888
oral, 886–887skin and digit, 888
uveal, 1388–1389
Melanoderma, 67
Melarsomine, 588
Melatonin, 70, 477
Melena , 889–890
Melia azedarach,  1453
Meloxicam
for pain management, 1022, 1466, 
1467
Melphalan, 29, 911
Memantine, 307
Menace response, 1508
Meningioma , 891–893
Meningitis , 894–895
Meningitis‐arteritis, steroid‐
responsive , 1294
Meningoencephalitis
bacterial, 894–895
necrotizing (NME), 963
Meningoencephalomyelitis
eosinophilic, 896
granulomatous (GME), 584, 897
of unknown etiology (MUE), 
897–898
Meningomyelitis, bacterial , 894–895
Mephyton. See Vitamin K1
N‐(2‐Mercaptopropionyl)‐glycine (2‐
MPG), 971, 1376–1377
Merle gene, deafness, 357
Merle ocular dysgenesis (MOD), 310, 
1195, 1197
Mesocestoides,  1317
Mesothelioma , 899
Mestinon. See Pyridostigmine
Metabolic acidosis , 12–13
Metabolic alkalosis , 63–64
Metabolic bone disorders , 900–901
Metabolic epidermal necrosis. See 
Superficial necrolytic dermatitis
Metabolic myopathies , 948–949
Metacam. See Meloxicam
Metadate. See Methylphenidate

Index  1619
Metaiodobenzylguanidine (MIBG), 
radioiodinated, 224
Metaldehyde toxicosis , 902
Metformin toxicosis , 903
Methadone
Methamphetamine toxicosis,  
72–73, 758
Methanol toxicosis, 473, 1464
Methazolamide, 1276, 1388
Methemoglobinemia , 904–905
in acetaminophen toxicosis, 10, 11
cyanosis in, 352, 353
Methicillin‐resistant pyoderma , 1164
Methicillin‐resistant staphylococci, 909, 
1164, 1292, 1293
Methimazole, 41, 710
Methocarbamol, 1450
for antidepressant toxicosis, 102
for metaldehyde toxicosis, 902
1170
Methomyl toxicosis, 1003
S‐Methoprene, 539
Methotrexate, 264, 1102, 1450
Methylcobalamin, 290
Methylene blue, 1450
for methemoglobinemia, 353, 905
Methylenedioxymethamphetamine 
(MDMA) toxicosis, 758
Methylphenidate, 72–73, 954
Methylprednisolone
thrombocytopenia, 1330for intervertebral disc disease, 786
4‐Methylpyrazole. See Fomepizole
Methylsulfonylmethane, 116
Methyltestosterone, 434
Methylxanthines
for feline asthma and bronchitis,  
128
toxicosis, 260–261, 1458
Metoclopramide
for chronic kidney disease, 276
for dysautonomia, 1108
for esophageal strictures, 468
for esophagitis, 470, 471
for mammary gland  
hyperplasia, 864
for metformin toxicosis, 903
Metoprolol
for ventricular premature complexes, 
1410
Metorchis albidus,  836
Metorchis bilis,  836
Metorchis conjunctus,  836
Metritis , 906Metronidazole
for acne, 381
895
syndrome, 263, 264
612, 615
toxicity, 689, 985
for trichomoniasis, 1357
for vomiting, 1427
Metyrapone, 1261
Mexican breadfruit, 1455
Mexican hairless dog, 67
Mexiletine
for cardiomyopathies, 227, 234
for hereditary myotonia, 945
1410, 1417
Mibolerone
for maternal behavior  
problems, 878
for pyometra, 1167
Micafungin, 123
Miconazole/chlorhexidine, 371
Microalbuminuria, 1138
Microcystins, 187
Microdontia, 1342
Microphthalmos, 310, 1325

1620  Index  
Microscopic examination
blood smears, 1492–1495
bone marrow aspirates, 1503–1506
urine sediment, 1565–1568
Microvascular dysplasia, hepatic. See 
Hepatoportal microvascular 
dysplasia
Micrurus fulvius  reactive antivenin, 1265
Midazolam
for beta‐2 agonist inhaler toxicosis, 172
Middening (fecal marking in cats), 
657, 659
Middle ear polyps, 955
Milbemycin oxime
for demodicosis, 362–363
toxicosis, 363, 792
Milbemycin oxime–lufenuron 
(Sentinel), 167
Milk of magnesia. See Magnesium 
hydroxide
Milk replacer, for neonates, 965, 966
Milk thistle. See Silymarin
Miltefosine, 824, 826
Mineralocorticoids, 720
Miniature American shepherd, cone 
degeneration, 310
Miniature dachshund
Miniature pinscher
Miniature poodle. See also  Poodle
alopecia X, 69
anal sac disorders, 77anemia, 89
atlantoaxial instability, 132
diabetic ketoacidosis, 395
optic nerve hypoplasia, 310
shoulder luxation, 793
skin tumors, 578, 886
urolithiasis/crystalluria, 348, 
970, 1372
Miniature schnauzer. See also  Schnauzer
aurotrichia, 372
cryptorchidism, 346
fibrocartilagenous embolic 
myelopathy, 130, 530
gallbladder mucocele, 265, 544
574
hyperlipidemia, 685, 686, 1374
hyperosmolarity, 692
infertility, 767iris atrophy, 790
megaesophagus, 883, 885, 1185
retinal disease, 1193, 1197
sick sinus syndrome, 1250, 1251, 
1252, 1256
1372
Minimum inhibitory concentration 
(MIC), 1483, 1484
Minocycline
for pemphigus, 386
Miosis, 92
Mirataz. See Mirtazepine
Mirtazepine
Misoprostol
for gastroduodenal ulceration, 
553, 890
for NSAID toxicosis, 982
Missing tooth/teeth , 1341
Mistletoe, 1455
Mithramycin, 673
Mitochondrial myopathies, 948, 949

Index  1621
Mitotane (op’‐DDD)
for glycogen‐type vacuolar 
hepatopathy, 575
for hyperadrenocorticism, 667, 670, 
671, 1261
monitoring therapy, 1444
Mitoxantrone
for adenocarcinoma, 29, 31
1286, 1287, 1289, 1291
Mitral stenosis, 156–158
Mitral valve, systolic anterior motion, 
1315–1316
Mitral valve disease, myxomatous , 
951–953
Mitral valve dysplasia (MVD), 154–155
Moccasin snake envenomation, 
1266–1267
Moisturizers, for exfoliative 
Monkshood, 1455
Monoclonal gammopathy, 1046
Monocytosis, 831
Monstera deliciosa,  775, 1455
Morning glory, 1455
Morphine
Mosapride, 549
Mosquito bite hypersensitivity, 956
Motion sickness, 221
Mountain laurel, 1455
Mounting behavior , 870–873
Movement disorders , 907
Moxidectin. See also  Imidacloprid/
moxidectin
toxicosis, 792
MTM1  gene, 944
Mucomyst. See N ‐acetylcysteine
Mucopolysaccharidoses , 908
Mucositis, oral, 1297Mud rash/mud fever, 369
Multicentric squamous cell carcinoma in 
situ (MSSCIS), 1288, 1289
Multidrug‐resistant infections , 909–910
Multiple myeloma , 911
Mupirocin
Murmurs, heart , 912–913
Muscarine mushroom poisoning, 916
Muscle condition score (MCS), 1431
Muscle phosphofructokinase deficiency, 
573, 948
Muscle rupture (tear) , 914–915
Muscular dystrophy, hereditary  
X‐linked , 947
Mushroom toxicoses , 916–919
Music, for anxiety, 220, 491, 492
Muzzle folliculitis and furunculosis, 
canine, 15
Muzzles, for veterinary visits, 493
Myasthenia gravis (MG) , 920–921
megaesophagus, 883–884
MyBPC gene mutations, 235, 237
Mycobacterial infections , 922–923
Mycobacterial panniculitis, 922
Mycobacteriosis, systemic non‐
tuberculous, 922, 923
Mycophenolate mofetil
Mycoplasma haemocanis,  607
Mycoplasma haemofelis,  607
Mycoplasma haemominutum,  607
Mycoplasmal conjunctivitis, 320
Mycoplasmosis , 924–925
hemotropic, 607–608
Mycoses, deep cutaneous , 360–361
Mycosis fungoides. See Cutaneous 
epitheliotropic lymphoma
Mycotoxicosis , 926–927
aflatoxin, 926
tremorgenic toxins, 927Mydriasis, 92
Myelodysplasia, 1276
Myelodysplastic syndromes , 928
Myelofibrosis, 1044
Myeloma, multiple , 911
Myelomalacia, spinal cord (ascending, 
descending, progressive) , 929
Myelopathy . See also  Cervical 
spondylomyelopathy
canine degenerative, 209–210
fibrocartilagenous embolic, 530–531
in intervertebral disc disease, 781, 782
paresis/paralysis in cats, 930–931
Myeloproliferative disorders , 932
Myocardial fibrosis, idiopathic, 146
Myocardial infarction , 933
Myocardial tumors , 934
Myocarditis , 935–936
Myoclonus , 937
familial reflex, 937, 946
Myoglobinuria , 604–605
Myokymia, 945
Myopathy , 938–949
endocrine, 941–942
focal inflammatory, 939–940
generalized inflammatory, 948–949
hereditary Labrador retriever, 943
hereditary myotonia, 944
hereditary Scottie cramp, 945
hereditary X‐linked muscular 
dystrophy, 938
metabolic, 946–947
noninflammatory, 941–947
Myosin binding protein C (MyBPC) 
mutations, 235, 237
Myositis
extraocular/orbital, 1001, 1002
inflammatory, 940–941
masticatory muscle, 938–939
Myotonia, hereditary , 945
Myotoxic mushroom poisoning, 
916–919
Myotubular myopathy, X linked, in 
Labrador retrievers, 943
Myxedema , 950
Myxedema coma , 950
Myxomatous mitral valve disease , 
951–953
N
N‐acetylcysteine (NAC)
for acetaminophen toxicosis, 11, 83

1622  Index  
for copper associated hepatopathy, 
329–330
hepatoprotective therapy, 642
for intoxications, 1451
for mycotoxicosis, 926
Nail and nailbed disorders. See Claw and 
clawfold disorders
Naloxone
for neonates, 429, 966
for opioid reversal, 758, 997, 1451
Naltrexone, 16
Nanophyetus salmincola,  1216
Naphazoline toxicosis, 759
Naproxen toxicosis, 981
Narcissus, 1455
Narcolepsy , 954
Narcotic analgesics. See Opioids
Nasal aspergillosis , 124–125
Nasal dermatoses, canine , 956–957
Nasal discharge , 958–959
Nasal hemorrhage. See Epistaxis
Nasal hyperkeratosis, idiopathic, 957
Nasal hypopigmentation, seasonal, 372, 
956–957
Nasal philtrum, proliferative arteritis of, 
Nasal planum squamous cell 
carcinoma , 1288
Nasal polyps , 955
Nasal solar dermatitis, 372, 384, 956, 957
Nasal tumors
adenocarcinoma, 32–33
fibrosarcoma, 534
squamous cell carcinoma, 1287–1288
Nasodigital hyperkeratosis, idiopathic, 376
Nasolacrimal drainage system obstruction
conjunctivitis, 319, 322
epiphora, 456, 457
Nasopharyngeal polyps , 955
Nasopharyngeal stenosis , 960
NCSU/DCM2  gene, 232, 1415
NCSU/PDK4/DCM1  gene, 232, 1415
Neck pain , 961–962
Necrolytic migratory erythema. See 
Superficial necrolytic dermatitisNecrotic arachnidism, 1275
Necrotizing encephalitis , 963
Necrotizing leukoencephalitis (NLE), 963
Necrotizing meningoencephalitis 
(NME), 963
Neomycin
612, 615
Neonatal care, early , 966–967
Neonatal conjunctivitis. See Ophthalmia 
neonatorum
Neonatal isoerythrolysis, 964
Neonatal mortality , 964–965
Neonatal resuscitation , 966–967
Neonicotinoid toxicosis , 968
Neoplastic effusions, 1527, 1528, 1529
Neorickettsia helminthoeca,  436, 1216
Neorickettsia risticii,  436
Neosporosis , 969
Neostigmine, 1265
Neosynephrine, 959
Nephroblastoma, 308, 309
Nephrolithiasis , 970–971. See also  
Urolithiasis
Nephrotic syndrome , 972–973
Nephrotoxic mushroom poisoning, 
916–919
Nephrotoxicity, drug‐induced , 
974–975
Nerve sheath tumors , 976
Nettle, 1455
Neuroaxonal dystrophy , 977
Neuromyotonia, 945
Neuronal ceroid lipofuscinosis, 1193
Neuropathic pain, 1022, 1468
Neutering. See Castration; 
Ovariohysterectomy
Neutropenia , 978–979
Neutrophilia, 831
Neutrophilic leukocytosis, 
Newfoundland
cystinuria, 308, 348, 970, 1376, 1568
ectopic ureter, 434
mitral valve disease, 154, 156, 1315
osteochondrosis, 1007pemphigus foliaceus, 385
Niacin, 686
Niacinamide
for vasculitis, 1400, 1402
Nicergoline, 296
Nicotiana tabacum,  1456
Nictitating membrane. See Third eyelid
Night, waking at , 476–477
Nikkomycin, 1091
Nitazoxanide, 347
Nitenpyram, 538, 968
Nitrofurantoin, 839
Nitroglycerin
236, 242
cats, 448
for valvular heart disease, 157, 952
Nitroprusside (sodium nitroprusside)
cats, 448
Nizatidine, 470, 549
NMDA antagonists. See also  
Amantadine; Ketamine
Nocardia , 17
Nocardiosis, cutaneous , 980
Nodular dermatofibrosis, 36, 1044
Nodular dermatoses, sterile ,  
382–383
Nodular granulomatous episclerokeratitis 
(NGE), 182, 458, 796, 797
Nodules, cutaneous, 380–381, 382
Noise phobias , 1323–1324
Noninflammatory alopecia, in dogs , 
67, 68, 69–70
Nonregenerative anemia , 87–88N‐acetylcysteine (NAC) ( cont’d )

Index  1623
Nonsteroidal anti‐inflammatory drug 
toxicosis , 981–982
Nonsteroidal anti‐inflammatory drugs 
(NSAIDs)
for chondrosarcoma, 269, 270
for cruciate ligament disease, 343
to, 552, 553
for hemangiosarcoma, 594, 595, 
596, 599
hematemesis due to, 601
for osteoarthritis, 116, 1470–1471
for osteochondrodysplasia, 901
for pain management, 1022, 1023, 
1466–1467
for panosteitis, 1034–1035
thyroid function testing and, 748
Norepinephrine, 79, 1244, 1246
Norfolk terrier
Normal values. See Reference values
Norwegian elkhound, 564
entropion, 449
glucosuria, 570osteochondrodysplasia, 900, 1006
renal disorders, 274, 308
skin tumors, 378, 578, 1289
Norwegian forest cat
glycogen storage disease, 573, 
948, 1107
Norwegian lundehund
chronic atrophic gastritis, 550
protein‐losing enteropathy,  
849, 1136
Norwich terrier
laryngeal disease, 812
movement disorders, 907
Notoedric mange , 983
Nova Scotia duck tolling retriever
894, 1294
systemic lupus erythematosus‐related 
disease, 845
Novolin N, 400
NSAIDs. See Nonsteroidal anti‐
inflammatory drugs
Nuclear maturation defects, anemia 
with, 89
NurtureCALM 24/7 collar, 50
Nutraceuticals. See Dietary supplements/
nutraceuticals
Nutritional bone disorders , 900–901
Nutritional cardiomyopathy ,  
239–240
Nutritional support. See also  Enteral 
feeding; Parenteral nutrition
for acquired portosystemic shunting, 
1116
for anorexia, 94
for hepatitis, 624, 628
Nystagmus , 984–985
Nystatin, 282, 1141O
Oatmeal, colloidal, for pruritus, 1142
Obesity , 986–987
Obstipation , 323–324
Occipital dysplasia, 313
Occipitoatlantoaxial malformations, 313
Ocicat
photoreceptor dysplasia, 310
Oclacitinib, 135, 538, 1143
Octopus plant, 1452
Octreotide
for apudomas, 111
for glucagonoma, 568, 635, 1306
for hypersomatotropism/acromegaly 
in cats, 700
Ocular anomalies, congenital , 310–312
Ocular melanoma. See Uveal melanoma
Oculoskeletal dysplasia (OSD), 
310, 1006
Odontoclastic resorptive lesions, feline 
Odontogenic tumors , 988–989
Odontoma , 990
Odynophagia, 422, 469
Ohio buckeye, 1454
Old English sheepdog
cerebellar disease, 247, 689
ivermectin sensitivity, 257, 363, 
792, 1221
pigmenturia, 604
Oleander toxicity, 225
Oliguria , 991–992
Ollulanus  infection , 993
Omega‐3 fatty acids (and fish oils)
for arthritis, 116, 1102, 1472
for hyperlipidemia, 686

1624  Index  
Omeprazole
liver, 114
for brachycephalic airway syndrome, 
191
for cardiac glycoside plant toxicosis, 225
for esophagitis, 464, 465, 468, 
470, 471
for exocrine pancreatic insufficiency, 
481
553, 890
for hepatitis, 625, 627, 629
for uremia, 160
Ondansetron
for acute hepatic failure, 615for acute kidney injury, 24
for gastroduodenal ulceration/
erosion, 553
for insoluble oxalate plant toxicosis, 
775
Onychodystrophy, 282
Onychomadesis, 282, 283
Onychomalacia, 282
Onychomycosis, 282, 283
Onychorrhexis, 282, 283
Ophthalmia neonatorum , 994–995
in cats, 320
in dogs, 322
Ophthalmologic exam, complete , 
1507–1511
Opiates/opioids toxicosis , 996–997
Opioids (narcotic analgesics)
for osteoarthritis, 1470
for pain management, 1022–1023, 
1465
toxicosis, 758, 996–997
Opisthorchis felineus,  836
Opisthorchis viverrini,  836
Oprelvekin, 1330
Opsoclonus, 984
Optic nerve hypoplasia, 310, 311
Optic nerve lesions, 184
Optic neuritis , 998–999
Oral cavity tumors
ameloblastoma, 71
chondrosarcoma, 271
fibrosarcoma, 533
melanocytic/melanoma, 886–887
odontogenic, 988–989odontoma, 990
squamous cell carcinoma, 1285, 1290, 
1291
undifferentiated malignant, 1000
Oral ulceration , 1297–1298
Orbifloxacin, 77, 412
Orbital abscess/cellulitis, 1001, 1002, 
1325
Orbital diseases , 1001–1002
Orbital myositis, 1001, 1002
Orbital neoplasms, 1001, 1002, 1325, 
1326
Orchiectomy. See Castration
Orchitis , 453
lymphocytic, 769
Organ or mass aspiration, ultrasound‐
guided , 1555–1558
Organophosphorus toxicosis , 
1003–1004
Oriental shorthair cat
Ornithine aminotransferase deficiency, 
1193, 1194
L‐Ornithine‐L‐aspartate, 613
Oronasal fistula , 1005
Orthostatic tremors, 1355, 1356
Osaterone acetate, 168, 1134
Oslerus osleri,  1190–1191
Osteoarthritis  (degenerative joint 
disease; DJD), 116–117
in cranial cruciate ligament disease, 
342–343
in elbow dysplasia, 438–439
in hip dysplasia, 647, 648–649
medications and supplements, 
1469–1472
Osteochondritis dissecans (OCD), 
1007–1008
elbow, 438–439
sacral, 841
Osteochondrodysplasia , 1006
Osteochondrosis , 1007–1008
Osteogenesis imperfecta (OI), 900–901
Osteomyelitis , 1009–1010
fungal, 122, 123, 1009, 1010
oral ulceration, 1297
vertebral. See Discospondylitis
Osteosarcoma , 1011–1012
Otitis externa and media , 1013–1014
Otitis media and interna , 1015–1016
Otodectes cynotis,  432
Otter hound, thrombasthenia,  
459, 1327
Outbreaks, disease, 1571
Ovarian remnant syndrome , 
1017–1018
Ovarian tumors , 1019Omega‐3 fatty acids (and fish oils) ( cont’d )

Index  1625
Ovariectomy (OVE)
for false pregnancy, 485
false pregnancy after, 485
ovarian remnant syndrome after, 
1017–1018
Ovariohysterectomy (OHE) (spay)
after termination of pregnancy, 7
mammary tumors and, 865, 866, 
867, 868
1017–1018
urinary incontinence after, 765, 766
Ovotesticular disorders of sexual 
development, 1238
Ovulation induction, 768, 1020
Ovulatory failure , 1020
Ovuplant, 768
Oxacillin, 1293
Oxalate (insoluble) plant toxicosis , 775
Oxalobacter formigenes,  1374
Oxazepam
Oxfendazole, 993
Oxitriptan, 1458
OxR2  gene, 954
Oxybutynin, 431, 766
Oxygen, partial pressure in blood (PO2), 
1485–1487
hypoxemia, 750
Oxygen therapy
syndrome, 25–26
for dyspnea and respiratory 
distress, 426
hyperbaric, 223, 1275
Oxymetazoline
topical nasal, 502, 959
toxicosis, 759Oxymorphone, 412, 491
Oxytetracycline
for Rocky Mountain spotted fever, 1205
Oxytocin
for spontaneous abortion, 5
P
P2Y12  (ADP) receptor mutation, 1327
p53 mutations, 378
Pacemakers, cardiac, 146–147, 1251, 
1257
Pagetoid reticulosis, 858
Pain, 1021–1024
acute, chronic, and postoperative, 
1021–1024
aggression due to, in cats, 49, 56
drug dosages and indications, 
1465–1468
neck and back, 961–962
neuropathic, 1022, 1468
Palatal defects , 1025–1026
Palatitis, 1297
Palladia. See Toceranib phosphate
Palpebral reflex, 1508
Pamidronate, 1451
Pancreatic acinar atrophy (PAA), 480
Pancreatic adenocarcinoma , 34
Pancreatic enzyme supplements, 
176, 481
Pancreatic insufficiency, exocrine , 
480–481
Pancreatic islet cell tumors
apudoma, 111
glucagonoma, 568–569
insulinoma, 776–778
Pancreatic polypeptidoma, 111
Pancreatitis , 1027–1030
acute, 1027, 1030
bile duct obstruction, 174
in cats, 1027–1028
chronic, 1027
in dogs, 1029–1030
peritoneal fluid analysis, 1477Pancytopenia , 1031–1032
Panepidermal pustular pemphigus/
pemphigus vegetans (PEP), 
1055–1056
Panniculitis , 1033
mycobacterial, 922
sterile nodular, 382, 383, 1033
Pannus (chronic superficial keratitis), 
796, 797
Panosteitis , 1034–1035
Panting , 1036–1038
Pantoprazole
liver, 114
for esophagitis, 464, 465, 470
553, 890
Papilledema , 998–999
Papillomas, cutaneous, 378
Papillomatosis , 1039
Papillon
Papulonodular dermatoses , 380–381
Paracentesis. See Abdominocentesis
Paracetamol. See Acetaminophen
Paragonimus kellicotti,  1190–1191
Paralysis , 1040–1041
coonhound, 326
intervertebral disc disease—cats, 780
intervertebral disc disease, cervical, 
781
intervertebral disc disease, 
thoracolumbar, 784

1626  Index  
laryngeal. See Laryngeal paralysis
myelopathy in cats, 930–931
tick bite, 1336–1337
Paranasal sinus
sinusitis, 1199–1201
squamous cell carcinoma, 1287
Paraneoplastic alopecia, feline , 
518, 1043
Paraneoplastic syndromes , 1042–1044
Paraparesis, 1040
Paraphimosis , 1045
Paraplegia, 1040
Paraprostatic cysts, 1131
Paraproteinemia , 1046
Paraquat toxicity, 1093
Parathormone, serum, 1445
Parathyroid tumors, 672, 694, 695
Parenteral nutrition. See also  Nutritional 
support
Paresis/paralysis in cats , 930–931
Paromomycin, 294, 347
Paronychia, 282, 283
Parotid mucocele, 1215
Paroxetine
48, 60
495, 497
1334
Parson Jack Russell terrier. See also  Jack 
Parvovirus infection
canine. See Canine parvovirus
Pasireotide, 700
Patellar luxation , 1047–1048
Patent ductus arteriosus (PDA) , 
1049–1051
Patent foramen ovale (PFO), 156
Patiromer, 684
Pausinystalia johimbe,  1457
Paxil. See ParoxetinePaxillus syndrome, 916–919
PDK4/NCSU/DCM1  gene, 232, 1415
Pearsonema (Capillaria) feliscati,  
1370, 1371
Pearsonema (Capillaria) plica,  1370, 
1371
Pectus excavatum , 1052
Pediatric behavior problems
in cats, 801–802
in dogs, 1155–1156
Peg tooth, 1342
Pekingese
necrotizing encephalitis, 963
squamous cell carcinoma of skin, 1289
subarachnoid cysts, 1302
Pelger–Huët anomaly , 1053
Pelodera  dermatitis, 381
Pelvic bladder , 1054
Pembroke Welsh corgi. See also  Welsh 
corgi
478
Pemoline toxicosis, 72–73
Pemphigoid
bullous, 385, 386
drug‐induced, 350
Pemphigus , 1055–1056
panepidermal pustular/vegetans, 
1055–1056
paraneoplastic, 1044, 1055–1056
Pemphigus erythematosus (PE), 
1055–1056
nasal, 956
Pemphigus foliaceus (PF), 1055–1056
depigmentation, 372, 373drug‐induced, 350
nasal, 956, 957
Pemphigus vulgaris (PV), 385, 386, 
1055–1056
Penciclovir, 502
Penicillamine (D‐penicillamine), 1449
330, 331
Penicillins
Penicillium  toxins, 927
Penitrem A toxicosis, 927
Pennyroyal oil, 472, 1457
Pentamidine, 1084
Pentatrichomonas  spp., 1357
Pentobarbital
1170
for seizures, 129
Pentoxifylline
Peppermint oil, 472, 1457
Pepto‐Bismol. See Bismuth subsalicylate
Periadnexal pyogranulomatous 
dermatitis, idiopathic, 1224
Perianal fistula , 1057
Pericardial disease , 1058–1060
Pericardial effusion, 1058–1060
in atrial wall tear, 144–145
idiopathic, 1058, 1059, 1060
in mesothelioma, 899
pericardiocentesis, 1534–1537
Pericardiocentesis , 1534–1537
Pericarditis
idiopathic hemorrhagic, 1058
infectious, 1058, 1059
Perineal hernia , 1061–1062
Periodontal disease , 1063–1064Paralysis ( cont’d )

Index  1627
Periodontitis, 1005, 1297
Peripheral edema , 1065–1066
Peripheral nerve sheath tumors (PNST), 
976, 1223
Peripheral nerve syndromes, 
Peripheral neuropathies , 1107–1108
Peripheral odontogenic fibroma (POF), 
988
Perirenal pseudocysts , 1067
Peritoneal dialysis, 24, 1099
Peritoneal fluid analysis , 1476–1478
Peritoneal larval cestodiasis (PLC), 1317
Peritoneopericardial diaphragmatic 
hernia , 1068
Peritonitis , 1069–1071
bile, 177–178
peritoneal fluid analysis, 1477–1478
Periuria (urine housesoiling), in cats, 657
Permethrin/pyrethrin, for flea 
control, 539
Permethrin toxicity, 1170
Persian cat
1115
aspergillosis, 122
atrioventricular block, 148
Chediak‐Higashi syndrome, 255, 
1327
depigmenting dermatoses, 372, 373
ductal plate malformation, 262, 416
exfoliative dermatosis, 376
1107
peritoneopericardial diaphragmatic 
hernia, 401, 1068
polycystic kidney disease, 308, 1105, 
1188
pulmonary carcinoma, 1286
sinus arrhythmia, 1254skin tumors, 165, 378, 578
tooth resorption, 522
1372
Persian violet, 1455
Persistent hyperplastic primary vitreous 
(PHPV), 310, 311
Persistent hyperplastic tunica vasculosa 
lentis (PHTVL), 310, 311
Persistent Müllerian duct syndrome 
(PMDS), 346, 1238
Persistent pupillary membranes 
(PPM), 310
Persistent right fourth aortic arch, 1399
Perthes disease, 820–821
Peruvian Inca Orchid, 67
Pet loss support resources, 1572
Petechiae , 1072–1073
Petit basset griffon Vendéen, glaucoma, 
564
Petroleum hydrocarbon toxicoses , 
1074–1075
Petting intolerance, in cats, 49, 56
PGF2α. See Prostaglandin F2αpH, arterial blood, 1485–1486
Pharyngeal sialocele, 1214, 1215
Pharyngitis, 1297
Pheasant’s eye, 1453
Phencyclidine (PCP) toxicosis, 758
Phenobarbital, 1449
513
for genetic epilepsy in dogs, 454, 455
for seizures/status epilepticus, 1120, 
1226, 1228for subarachnoid cysts, 1303
toxicity, 1228
Phenols, toxic exposures, 1463
Phenothiazines
1334
Phenoxybenzamine
for tick bite paralysis, 1337
Phentermine (ADD/ADHD medication) 
Phenylephrine
nasal spray, 270, 534
for priapism, 1045
Phenylephrine toxicosis , 1144
Phenylpropanolamine
for ectopic ureter, 434
for retrograde ejaculation, 770
Phenytoin, 945
Pheochromocytoma , 1076–1077
48, 60
for destructive and scratching 
behavior, 388
495, 497
for feline aggression, 50, 54, 57
804
1334
for urine marking in cats, 658
for veterinary visits, 490, 492
Philodendron  spp., 775, 1456
Phimosis , 1045
Phlebitis , 1401–1403
Phlebotomy, therapeutic, 462–463, 1106
Phobias , 494–497
thunderstorm and noise, 1333–1334
Phoenix abscess, 1343
Phoradendron  spp., 1455
PhosChol. See Polyunsaturated 

1628  Index  
Phosphate binders, 696, 699
Phosphate supplementation, 396, 618, 
740
Phosphatidylcholine, polyunsaturated. 
Phosphide rodenticide toxicosis ,  
1211
Phosphodiesterase type III 
inhibitors, 705
Phosphodiesterase type V inhibitors, 705
Phosphofructokinase (PFK) 
deficiency , 1078
anemia, 90, 91
myopathy, 946
Phosphorus supplementation. See 
Phosphate supplementation
Photodermatitis, 384
Photodynamic therapy, for squamous cell 
carcinoma, 1285, 1288
Photoreceptor degeneration, 1193
Photoreceptor dysplasia, 310, 1193
Phthisis bulbi, 1325
Phycomycosis. See Pythiosis
Physaloptera  spp., 1523
Physalopterosis , 1079
Physiologic measurements, normal 
ranges, 1447
Physostigmine, 688, 792
Phytomenadione. See Vitamin K1
Phytonadione. See Vitamin K1
Pica, 332–333
PICALM gene, 106
Piebald gene, 357
Pigmentary keratitis, 796, 797
Pigmentary keratopathy of pugs, 
796, 797
Pigmentary uveitis of golden retrievers, 
100
Pigmented viral plaques, canine, 1039
Pigmenturia, 604–605
PIGN  gene, 907
Pilocarpine, 800
Pilomatricoma, 578
Pimecrolimus, 373, 797
for cardiomyopathy, 230, 233, 236, 
242
for congestive heart failure, 121, 316, 
318
157, 952Pine oils, 472, 1457, 1463
Pinnal alopecia/pattern baldness, 67, 68
Pinnal squamous cell carcinoma, 1284
Pinscher. See Affenpinscher; Doberman 
pinscher; Miniature pinscher
Piroplasms, 161
Piroxicam
for adenocarcinoma, 33, 39
596, 599
for squamous cell carcinoma, 1283, 
1285, 1286, 1287, 1290, 1291
for transitional cell carcinoma, 431, 
1351
Pit bull terrier. See also  American pit bull 
terrier
acne, 15
Pit viper envenomation , 1266–1267
Pituitary dwarfism, 741
Pituitary tumors, 194
hyperadrenocorticism, 667, 668, 
669–670, 671
PKLR  gene mutations, 1171
Placenta, retained , 1192
Placental sites, subinvolution of , 1304
Plague , 1080
Plants, toxic home and garden, 
1452–1456
Plasma
for failure of passive transfer, 966
fresh frozen. See Fresh frozen plasma
platelet‐rich, intra‐articular injection, 
116, 1249
Plasmacytoma, mucocutaneous , 1081
Plasmoma, 1325, 1326
Plastic dish dermatitis, 373, 956
Platelet‐derived growth factor 
antagonists, 705
Platelet function defects. See 
Thrombocytopathies
Platelet‐rich plasma, intra‐articular 
injection, 116, 1249
Platelet transfusions
for Chediak-Higashi syndrome, 255
for thrombocytopathies, 1326for thrombocytopenia, 1327–1328, 
1329
Platynosomum concinnum,  836
Play, excessive, in kittens, 801, 802
Play aggression
in cats, 49, 56
in dogs, 58
in kittens, 801–802
Playbiting, by puppies, 1155, 1156
Pleural effusion , 1082–1083
in dilated cardiomyopathy, 229–230
point-of-care ultrasonography, 1546
thoracocentesis and fluid analysis, 
1550–1552
Pleural fluid analysis , 1550–1552
Pleural line, 1544
Pleural space and lung point-of-care 
Pleurocentesis. See Thoracocentesis
Plott hound, mucopolysaccharidosis, 908
Pneumocystosis , 1084
Pneumonia , 1085–1093
aspiration. See Aspiration pneumonia
bacterial, 1086–1087
endogenous lipid (EnLP), 1092, 1093
eosinophilic, 1088–1089
fungal, 1090–1091
interstitial, 1092–1093
secondary to influenza, 773–774
ventilator‐associated, 26
Pneumonyssoides caninum,  1190–1191
Pneumoperitoneum, 1539–1540
Pneumothorax , 1094–1095
point-of-care ultrasonography, 
1545–1546
Pododermatitis , 1096–1097
Poinsettia, 1456
Point-of-care abdominal 
Point-of-care pleural space and lung 
Pointer. See also  English pointer; German 
shorthaired pointer; German 
wirehaired pointer
Poisoning. See Intoxication
Poisoning (intoxication) therapy , 
1098–1099
Polioencephalomyelitis, in cats , 1100
Poliosis, 372
Polish hound (ogar), thrombocytopenia, 
1327, 1494
Pollakiuria , 430–431
Polyarteritis, juvenile, in beagles, 74, 
1401
Polyarteritis nodosa, 1401

Index  1629
Polyarthritis , 1101–1104. See also  
Arthritis
erosive, immune‐mediated, 
1101–1102
feline periosteal proliferative, 1101, 
1102
immune‐mediated, in dogs, 
1103–1104
nonerosive, immune‐mediated, dogs, 
1103–1104
Polycystic kidney disease (PKD) , 1105
disease, 308
ductal plate malformation, 416–417
renomegaly, 1188
Polycystin‐1 precursor gene, 416
Polycythemia. See also  Erythrocytosis
Polycythemia vera , 1106
erythrocytosis, 462, 463
Polydipsia (PD) , 1113–1114
Polyethylene glycol (PEG)
for megacolon, 881, 882
Polymyositis, 940–941
Polymyxin B, 183, 338
Polyneuropathies , 1107–1108
Polyphagia , 1109–1110
Polypoid cystitis , 1111–1112
Polyradiculoneuritis. See also  Coonhound 
paralysis
acute canine idiopathic, 326–327
postvaccinal, 326, 327
Polysulfated glycosaminoglycans 
(PSGAGs)
Polyunsaturated phosphatidylcholine 
(PPC) (PhosChol), 281, 
330, 624
Polyuria (PU) , 1113–1114
POMC  gene mutations, 986
Pomeranian
pneumocystosis, 1084pulmonic stenosis, 1153
malformation, 1276, 1312
Pompe’s disease (acid maltase deficiency), 
573, 948
Ponazuril
for coccidiosis, 214, 294, 509
Poodle. See also  Miniature poodle; 
Standard poodle; Toy poodle
alopecia, 67, 69
anemia, 90
otitis, 1013, 1015
skin tumors, 165, 378, 578, 888, 1289
thrombocytopenia, 1072
Porphyria, feline congenital, 90
Portal hypertension , 701–703
acquired portosystemic shunts, 1115
in arteriovenous malformation  
of liver, 113
Portosystemic shunting, acquired 
(APSS) , 1115–1117
hepatic encephalopathy, 611, 612, 613
urate urolithiasis, 1383
Portosystemic vascular anomaly 
(PSVA), congenital , 1118–1121
hepatoportal microvascular dysplasia 
(MVD) and, 639, 641Portuguese water dog
Posaconazole
Postclipping alopecia, 67
Postoperative pain , 1021–1024
Postvaccinal polyradiculoneuritis, 
326, 327
Potassium bromide (KBr), 129, 455, 613
Potassium chloride (KCl)
for beta‐2 agonist inhaler toxicosis, 172
for hypokalemia, 730
Potassium citrate
for Fanconi syndrome, 489
for urolithiasis, 971, 1373, 1374, 1376
Potassium gluconate, 275, 730
Potassium phosphate, 172, 618, 740
Potassium supplementation
for hypokalemia, 729–730
Potpourri, liquid, 1457
Poxvirus infection, in cats , 1122
Pradofloxacin
Pralidoxime chloride (2‐PAM), 1004, 
1451
Praziquantel
Prazosin

1630  Index  
for stranguria, 431
Pre‐iridal fibrovascular membranes 
(PIFM), 717
Prebiotics, 528, 1263
Precatory bean, 1456
Precordial thump, 1308, 1405
Predatory aggression
in cats, 54, 56
in dogs, 58
for blind quiet eye, 184
for brachial plexus avulsion, 189
830
for eosinophilic granuloma, 452
513
for inflammatory bowel disease, 404, 
772
for inflammatory/immune colitis, 301for interstitial pneumonia, 1093
for lymphoma, 855, 858
Prednisone
for anaphylaxis, 1066
for chondrosarcoma, 270
830
for encephalitis, 443for eosinophilic 
513
for fibrosarcoma, 534
for inflammatory bowel disease, 406, 
557, 772
for optic neuritis and papilledema, 
998
1205
for thymoma, 1335Prazosin ( cont’d )

Index  1631
for toxoplasmosis, 1347
Pregabalin
Pregnancy
early loss
edema in the bitch, 1123–1124
false, 485–486
premature labor, 1126
termination, 6–7
toxemia, 1125
Premature labor , 1126
Previcox. See Firocoxib
Priapism , 1045
Primaquine, 162
Primary ciliary dyskinesia (PCD), 198, 
769, 1273
Primitive neuroectodermal tumors, 195
Primordial cyst, 366
Probiotics
48, 60
for feline herpetic conjunctivitis, 320
1158
Procainamide
for myotonia, 945
1417
Procedures and testing protocols, 
1475–1568Prochlorperazine, 601
Proctitis , 300–302
Progesterone
serum or plasma, 196, 197, 1445
Progestogens, 1126
Progressive retinal atrophy (PRA), 184, 
1193, 1194
ProHeart. See Moxidectin
Prokinetic agents
Prolapsed gland of third eyelid , 1127
Propantheline
for dysuria, pollakiuria, and 
stranguria, 431
Propentofylline, 296
Propionibacterium acnes,  507, 515
Propofol
for postoperative seizures, 1120
1170
Propranolol
for tetralogy of Fallot, 1322for toad venom toxicosis, 1340
1410
Proprioceptive (sensory) ataxia, 130
Proptosis , 1128
Propylene glycol, 377, 380, 1224
Propylthiouracil, 710
Prostaglandin E1. See Misoprostol
Prostaglandin F2α (PGF2α) (dinoprost)
for termination of pregnancy, 6, 7
Prostate adenocarcinoma , 35
Prostate disease in breeding male dog , 
1129–1130
Prostatic abscess , 1132–1133
Prostatic cysts , 1131
Prostatic hyperplasia, benign. See Benign 
prostatic hyperplasia
adenocarcinoma, 35
Prostatitis , 1132–1133
Prostatomegaly , 1134–1135
Protamine sulfate, 1451
Protamine zinc insulin (PZI), 
397–398, 400
Protein‐losing enteropathy (PLE) , 
1136–1137
Protein‐losing nephropathy. See 
Glomerulonephritis
Protein restriction, dietary, 612, 624, 
1119
Proteinuria , 1138–1140
in amyloidosis, 75
in glomerulonephritis, 566, 567
in nephrotic syndrome, 972
Proton pump inhibitors. See also  
Omeprazole; Pantoprazole
liver, 114
204

1632  Index  
553, 890
Protopam. See Pralidoxime chloride
Prototheca  spp., 300
Protothecosis , 1141
Prozac. See Fluoxetine
Prucalopride, 549
Pruritus , 1142–1143
in acral lick dermatitis, 16
anal/perianal, 77
in atopic dermatitis, 134, 135
Pseudo‐urolithiasis (dried blood, 
ossified material) , 1378
Pseudoanorexia, 94
Pseudochylous effusion, 277
Pseudocyesis. See Pseudopregnancy
Pseudoephedrine, 770
Pseudoephedrine toxicosis , 1144
Pseudohermaphrodite, 1238
Pseudohyperkalemia, 683
Pseudomacrothrombocytopenia , 1145
Pseudopregnancy (false pregnancy) , 
485–486
Pseudoptyalism, 1146
Pseudothrombocytosis, 1333
Psilocybin poisoning, 916
Psoas muscle injury, 914, 915
Psychoactive isoxazole mushroom 
Psychogenic alopecia, 66, 304–305
Psyllium, 285, 528–529, 882
PTPLA  gene, 944
Ptyalism , 1146–1147
Pug
brachycephalic airway syndrome, 1295
eyelid/eyelash disorders, 182, 482
hydrocephalus, 663idioventricular rhythm, 754
pigmentary keratopathy, 796, 797
seizures/status epilepticus, 1227
sinus bradycardia, 1256
Puli, deafness, 357
Pulling behavior, dogs , 1361–1362
Pulmonary alveolar proteinosis (PAP), 
1093
Pulmonary contusions , 1148
Pulmonary edema , 1149–1150
in dilated cardiomyopathy, 230, 233
in hypertrophic cardiomyopathy, 235
noncardiogenic, 1149–1150
Pulmonary fibrosis, idiopathic (IPF), 
1092–1093
Pulmonary hypertension , 704–705
in atrioventricular valve stenosis, 156
Pulmonary thromboembolism (PTE) , 
1151–1152
Pulmonic stenosis , 1153–1154
Pulse oximetry, 750
Pupillary abnormalities, congenital, 310
Pupillary light reflex, 1508
Pupils, asymmetric, 92–93
Puppy behavior problems ,  
1155–1156
Puppy socialization and puppy classes , 
1157–1158
Puppy strangles (juvenile cellulitis) , 
1159
Pure red cell aplasia (PRCA), 80
Purina® ProPlan Bright Mind 7+, 296Purina® ProPlan Veterinary Diets NC 
NeuroCare, 296
Purina® Veterinary Diets FortiFlora 
Canine Nutritional 
Supplement, 537
Pustules, 385
Pyelonephritis , 1160–1161
Pyloric gastropathy, chronic 
hypertrophic , 714–715
Pyoderma , 1162–1164. See also  Bacterial 
(staphylococcal) folliculitis
deep, 380, 1162
in hypothyroidism, 747
methicillin‐resistant, 1164
mucocutaneous, 372, 956
superficial, 380, 385, 1162
Pyogranuloma, 382, 383
Pyogranulomatous periadnexal 
Pyometra , 1165–1167
vaginal discharge, 1392
Pyothorax , 1168–1169
Pyrantel pamoate
Pyrazinamide, 923
Pyrenean mountain dog. See Great 
Pyrenees
Pyrethrin and pyrethroid toxicosis , 
1170
Pyrethrin/pyrethroids, 539, 826
Pyrexia. See Fever
Pyridostigmine (Mestinon), 921, 1041, 
1451
Pyridoxine (vitamin B6), 1451
for calcium oxalate urolithiasis, 1373
Pyrimethamine
leucovorin with, 1450
Pyriproxyfen, 539
Pyruvate dehydrogenase phosphatase I 
deficiency, 948
Pyruvate kinase (PK) deficiency ,  
1171
anemia, 90, 91Proton pump inhibitors ( cont’d )

Index  1633
Pythiosis (phycomycosis) , 1172–1173
cutaneous, 1172, 1173
gastrointestinal, 300, 301, 1172, 1173
Pythium insidiosum,  1172
Pyuria , 1174–1175
PZI Vet insulin, 400
Q
Q fever , 1176
Quadriceps contracture, 914, 915
Quadrigeminal cyst , 1177
Quadriparesis, 1040
Quadriplegia, 1040
Quaternary ammonium compounds, 
1460
Queensland blue heeler, lysosomal 
storage disease, 689
Quinidine, 138
Quinolones. See also  Fluoroquinones
R
Rabacfosadine, 857, 858
Rabies , 1178–1179
dysphagia, 423, 424
encephalitis, 443
head pressing, 581–582
Rabies vaccine vasculitis, 67
Raccoon roundworm, 167
Radial physeal closure, premature, 96, 97
Radiation therapy
for adenocarcinoma, 29, 31, 32–33, 
37, 38
for chemodectoma, 256
for chondrosarcoma, 269, 270, 271
for fibrosarcoma, 533, 534
for hemangiosarcoma, 596
for lipoma, 835
861
for odontogenic tumors, 988, 989
for oral tumors, 1000
1287, 1288
Radiculopathy, 781Radiographic contrast agents, 
Radioiodine (131iodine) therapy, 40, 
41, 710
Radiophosphorus (32P) therapy, 932
Radius, congenital agenesis of, 96
Ragdoll cat
Raisin toxicosis , 577
Ranitidine
erosion, 890
Rat terrier, hypomyelination, 733
Rattler antivenin, 1266–1267
Rattlesnake envenomation, 1266–1267
Reactive histiocytosis, 382, 650, 652
Recognition failure‐related aggression, in 
cats, 53
Rectal adenocarcinoma , 39
Rectal prolapse , 1180
Rectal scraping and cytology , 1547
Rectal stricture , 1181
Rectoanal polyps , 1182
Red eye , 1183–1184
Red urine, diagnostic algorithm, 603
Redirected aggression, in cats, 49, 53, 56
Reference values
electrocardiogram, 1448
endocrine testing, 1445
laboratory tests, 1441–1443
physiologic measurements, 1447
Regenerative anemia , 90–91
Regurgitation , 1185–1186
Renal adenocarcinoma , 36
Renal agenesis, 308
Renal cystadenocarcinoma, 36, 308, 309
Renal disease. See Kidney disease
Renal dysplasia, 274, 308, 309
Renal ectopia, 308, 309
Renal secondary hyperparathyroidism , 
696–697Renal telangiectasia, 308, 309
Renal tubular acidosis (RTA) , 1187
Renal tumors, 36, 1188
Renomegaly , 1188–1189
Repetitive behaviors, abnormal. See 
Compulsive disorders
Resource guarding, aggressive canine , 
51–52
Respiratory disease, canine infectious , 
215–216
Respiratory distress , 425–427
Respiratory infections, feline upper , 
524–525
Respiratory parasites , 1190–1191
Respiratory sinus arrhythmia, 1254, 
1255
Resting energy requirements (RER), 
1432
Restraint, of difficult patients, 490, 
491, 492
Restrictive cardiomyopathy, feline , 
241–242
Resveratrol, 1389
Retained placenta , 1192
Retching (gagging) , 1268–1269
Retinal degeneration , 1193–1194
Retinal detachment , 1195–1196
blind quiet eye, 184, 185
cataracts, 246
congenital, 311
Retinal dysplasia, 310, 1195, 1197
Retinal dystrophies, 310, 311
Retinal hemorrhage , 1197–1198
Retinochoroiditis, 272
Retinoids. See also  Isotretinoin
for sebaceous adenitis, 380
Retinol. See Vitamin A
Retrievers
eyelid/eyelash disorders, 435, 482
Retrograde ejaculation, 769, 770
Reverse sneezing , 1268–1269
Revolution. See Selamectin
Rex cats. See also  Cornish Rex; Devon Rex
Rheumatoid arthritis, 1101
Rhinella  toad intoxication, 1340
Rhinitis , 1199–1201
Rhinosporidiosis, 460, 1199
Rhipicephalus sanguineus,  161, 436, 
1204, 1338

1634  Index  
Rhodesian ridgeback
ventricular arrhythmias, 1404, 1409, 
Riboflavin (vitamin B2), 949
Ricinus communis,  1452
Rickets, 724
Rickettsia rickettsii,  1204–1205
Rifampin, 437, 453, 923
Rifaximin, 176, 612, 615
Right bundle branch block , 
1202–1203
Right ventricle, double‐chambered, 1153
Rimadyl. See Carprofen
Ringworm. See Dermatophytosis
Ritalin. See Methylphenidate
Rivaroxaban
Roaming behavior , 870–873
for anterior uveitis, 99
Rocky Mountain spotted fever , 
1204–1205
Rod‐cone dysplasia, 310, 311, 1193
Rodenticide toxicosis , 1206–1211
anticoagulants, 1206–1207
bromethalin, 1208
cholecalciferol, 1209–1210
phosphides, 1211
Roferon. See Interferons
Ronidazole, 301, 509, 1357
Roquefortine toxicosis, 927
Rosary pea, 1456
Rottweiler
acne, 15
anemia, 90
cervical spondylomyelopathy, 
252, 961
chronic diarrhea, 405claw and clawfold disorders, 282
cough, 339
eosinophilic 
meningoencephalomyelitis, 
442, 896
glomerulopathy, 308, 1138
histiocytic diseases, 378, 382, 
650, 652
hypereosinophilic syndrome, 678
leukoencephalomyelopathy, 833
Rough‐coated collie
exocrine pancreatic insufficiency, 480
552
vesicular lupus, 374
Roundworms , 1212Royal Canin Calm diet, 55, 497
Royal Canin Multifunction Urinary + 
Calm Diet, 50, 659
Royal Canin SO, 1373
Russian blue cat
Rutin, 278, 1066
S
S‐adenosylmethionine (SAMe)
266
for feline aggression, 57
Saarloos wolfhound, hypopituitarism, 
741
Sacral osteochondritis dissecans, 841
Sacrococcygeal dysgenesis, 313
Sago palm toxicosis , 1213
Saint Bernard
acromegaly, 900
arteritis of nasal philtrum, 372, 956, 
1400, 1401

Index  1635
1393, 1394
St John’s wort, 1458
Salbutamol. See Albuterol
Salicylate toxicosis, 1458
Salicylic acid, 14
Saline agglutination test , 1548–1549
Salivary gland adenocarcinoma , 37
Salivary mucocele , 1214–1215
Salmeterol toxicosis, 172
Salmon poisoning disease , 1216
Salmonellosis , 1217–1218
Salt toxicosis , 1219–1220
Saluki
dysmetria, 689
SAMe. See S‐adenosylmethionine
Samoyed
cerebellar disease, 130, 247,  
248, 689
372, 956, 1390
San Joaquin Valley fever. See 
Sarcoids, feline, 1039
Sarcopenia, 1431
Sarcoptic mange , 1221SARDS. See Sudden acquired retinal 
degeneration syndrome
Sarolaner, 538, 1339
Sartorius muscle injury/fibrosis, 914
Savannah cat, pyruvate kinase deficiency, 
1171
Schefflera actionphylla,  775
Schiff–Sherrington phenomenon , 1222
Schipperke
pemphigus foliaceus, 385
Schirmer tear test (STT), 1508–1509, 
1511
Schistosoma haematobium,  836
Schistosoma japonicum,  219, 836
Schistosomiasis, canine , 219
Schnauzer. See also  Giant schnauzer; 
Miniature schnauzer
subcorneal pustular dermatosis, 385
Schutzhund, missing teeth, 1341
Schwannoma , 1223
Scleral lacerations , 334–335
Scott syndrome, 459, 1327
Scottie. See Scottish terrier
Scottie cramp, hereditary , 946
Scottish deerhound
Scottish fold cat
urolithiasis, 970, 1372
Scottish terrier (Scottie)
alkaline hyperphosphatasemia, 61, 62
cystinuria, 1568
574
hepatocellular dysplastic hyperplasia, 
620, 621
hereditary cramp, 946
myocardial tumors, 934obesity, 986
primary renal glucosuria, 308, 570
skin tumors, 378, 888, 1289
1429
Scratching behavior, in cats , 388
kittens, 801, 802
Sealyham terrier
retinal dysplasia, 1193, 1197
Seasonal flank alopecia, 67
Seasonal nasal hypopigmentation, 372, 
956–957
Sebaceous adenitis, granulomatous , 1224
scaling, 376
Sebaceous gland adenocarcinoma , 38
Sebaceous gland dystrophy, 65
Sebaceous gland tumor, 378
Seborrhea, primary idiopathic, 376, 377
Sedation
Seizures , 1225–1229. See also  Epilepsy
1473–1474
in meningioma, 892
postoperative, 1120
Selamectin
for nasal mites, 1269
(SSRI) toxicosis , 102–103
Selective serotonin reuptake inhibitors 
(SSRIs)
48, 60

1636  Index  
495, 497
for feline aggression, 49, 50, 54, 57
1233
1334
Selegiline (L‐deprenyl)
296
for narcolepsy/cataplexy, 954
Semimembranosus muscle contracture, 
914, 915
Seminoma , 1230
Semitendinosus muscle contracture, 
914, 915
Sensory neuropathy, 1107
Sensory (proprioceptive) ataxia, 130
Sentinel (milbemycin oxime–lufenuron), 
167
Separation anxiety syndrome , 
1231–1234
Sepsis , 1235–1236
Septic arthritis , 118–119
Septic shock , 1245–1246
SERAC1  gene, 907
Serotonin 2 α antagonist/reuptake 
inhibitors, for aggression, 43, 
45, 48
Serotonin and norepinephrine 
reuptake inhibitor (SNRI) 
toxicosis , 102–103
Serotonin syndrome, 102, 1458
Sertoli cell tumor , 1237
Sertraline
48, 60
for feline aggression, 49
Serum
Sevelamer hydrochloride, 699
Severe combined immunodeficiency, 760Sex chromosome disorders of sexual 
Sexual aggression, in cats, 53–54
Sexual development disorders , 
1238–1239
Sézary syndrome, 858
Shaker/tremor syndrome, 
corticosteroid responsive , 1240
“Shaking puppies,” 733
Shampoos
Shar‐pei
cobalamin malabsorption, 87, 290
gastroesophageal reflux, 558
histiocytic diseases, 378, 652
IgA deficiency, 760
meat‐mouth phenotype, 74, 487
Shar‐pei autoinflammatory disease 
(SPAID). See Shar‐pei fever, 
familial
Shar‐pei fever, familial , 487–488
amyloidosis, 74–75
polyarthritis, 1103, 1482
renal amyloidosis, 74–75, 308
Shar‐pei swollen hock syndrome. See 
Shar‐pei fever, familial
Shell teeth, 1342
Shetland sheepdog (sheltie)
anemia, 90
corneal dystrophy, 337craniomandibular osteopathy, 341
dermatomyositis, 367, 374, 385, 940, 
956
574
histiocytic diseases, 378, 650, 652
1221
lupus erythematosus, 372, 374, 385, 
844, 845, 956
nodular episclerokeratitis, 458, 796
renal disorders, 308, 566
retinal disease, 1193, 1195, 1197
uveodermatologic syndrome, 100
von Willebrand disease, 1072, 1429
Shiba Inu
Shih tzu
hepatocutaneous syndrome, 634–635
639, 640
intervertebral disc disease, 781, 784
skin tumors, 378Selective serotonin reuptake inhibitors 
(SSRIs) ( cont’d )

Index  1637
Shipping, resources, 1572
Shock , 1241–1246
cardiogenic, 1241–1242
hypovolemic, 1243–1244
septic, 1245–1246
Shoulder joint, ligament and tendon 
conditions , 1247–1249
Shoulder luxation, 793
Shropshire terrier, deafness, 357
Sialocele, 1214–1215
Siamese cat, 733
anemia, 90
asthma and bronchitis, 127, 200, 
339, 352
compulsive disorders, 304
corneal sequestrum, 338, 798
destructive and scratching 
behavior, 388
lymphoma, 854
1107
pancreatitis, 1027
paraphimosis, phimosis, and priapism, 
1045
paresis/paralysis, 930pemphigus foliaceus, 1055
pica, 332
salivary gland adenocarcinoma, 37
Siberian cat, pyruvate kinase deficiency, 
1171
Siberian husky
alkaline hyperphosphatasemia, 61
eosinophilic granuloma, 382, 451
eosinophilic pneumonia, 1088
laryngeal paralysis, 1295
pneumothorax, 1094
272, 956, 1390
zinc‐responsive dermatosis, 182, 376, 
956
Sick sinus syndrome , 1250–1251
Sighthound
blood pressure, 1489
periodontal disease, 1063
Sildenafil
for congestive heart failure, 318
for pulmonary hypertension, 353, 705
1152
Silibinin. See Silymarin
Silken windhound, ivermectin 
sensitivity, 792Silky terrier
Silymarin (silybin; silibinin; milk thistle)
for mushroom toxicosis, 918–919
Simethicone, 537
Singapura cat, pyruvate kinase deficiency, 
1171
Sinoatrial block , 1252–1253
Sinus arrest , 1252–1253
Sinus arrhythmia , 1254–1255
Sinus bradycardia , 1256–1257
Sinus tachycardia , 1258–1259
Sinusitis , 1199–1201
Sistrurus  spp. envenomation, 1266–1267
Sjögren‐like syndrome , 1260
Skeletal malocclusion , 862–863
Skin disorders. See Dermatoses
Skin fragility syndrome, feline , 1261
Skin tumors (neoplastic dermatoses) , 
378–379
feet, 1096, 1097
hemangiosarcoma, 596–597
mast cell tumors, 378, 874–875
squamous cell carcinoma, 1289
sweat gland/sebaceous 
adenocarcinoma, 38
Skye terrier
SLC3A1  gene mutations, 1376
SLC7A9  gene mutations, 1376
Sleep aid toxicosis , 169–170
SLGA5  gene, 907
Sloughi dog, rod cone dysplasia, 310
Slug bait poisoning, 902
Small intestinal bacterial overgrowth 
(SIBO), 402, 1262
Small intestinal dysbiosis (SID) , 
1262–1263
Small intestinal obstruction, 559–560
Small intestinal tumors
leiomyosarcoma, 823

1638  Index  
SMOC ‐2 gene, 194
Smoke inhalation , 1264
Smooth fox terrier
Smooth‐haired miniature dachshund, 
Snail bait poisoning, 902
Snake venom toxicosis , 1265–1267
coral snakes, 1265
pit vipers, 1266–1267
Sneezing , 1268–1269
Snowshoe cat, axonal neuropathy,  
1107
SNRI (serotonin and norepinephrine 
reuptake inhibitor) toxicosis , 
102–103
Soaps, toxicity, 1460–1461
Socialization (and classes)
kitten, 803–804
puppy, 1157–1158
SOD1  mutations, 209
Sodium bicarbonate (NaHCO3)
1413
for hyperchloremia, 676
for hyperkalemia, 683, 684
for metabolic acidosis, 13
Sodium hypochlorite, for 
Sodium nitroprusside. See Nitroprusside
Sodium phosphate, 740
Sodium restriction, dietary
for ascites, 121, 703, 1116
for congestive heart failure, 315, 318
Sodium sulfate
Sodium urate crystalluria, 348
Sodium zirconium cyclosilicate, 684Soft‐coated wheaten terrier
chronic diarrhea, 405
food allergies, 542
glomerular disease, 308, 566, 1138
movement disorders, 907, 946
Soft tissue sarcoma , 1270–1271
Solanum pseudocapsicum,  1454
Solanum tuberosum,  1454
Solar dermatitis, 384
Solar‐induced skin tumors, 1289
Solar‐induced thermal burn, 384
Solganal, 519
Solliquin, 50
Solvents, toxic exposures, 1464
Somali cat
anemia, 90
retinal disease, 310, 1193
Somatostatin analogs. See also  Octreotide
Somatropin. See Growth hormone
Sorbitol
1208
Sotalol
1410, 1417
Sowbread, 1455
Spaniels. See also specific types of spaniel
Spastic pupil syndrome, 92
Spathiphyllum  spp., 775
Spay. See Ovariohysterectomy
Sperm granuloma , 1272
Spermatic cord, torsion of , 1345Spermatocele , 1272
Spermatozoal abnormalities , 1273
Spherulocytosis, 382, 383
Sphynx cat
Spider venom toxicosis , 1274–1275
black widow, 1274
brown recluse, 1275
Spike’s disease. See Canine epileptoid 
cramping syndrome
Spina bifida, 313, 314
Spinal cord injury (SCI), 1419–1420
atlantoaxial instability, 132–133
myelomalacia after, 929
paralysis in cats, 931
Schiff–Sherrington phenomenon, 1222
Spinal cord lesions. See also  Myelopathy
cervical spondylomyelopathy, 252–253
congenital, 313–314
Spinal cord meningioma, 891, 892, 893
Spinal cord myelomalacia (ascending, 
descending) , 929
Spinal dysraphism , 1276–1277
Spinal malformations, congenital , 
313–314
Spinal muscular atrophy, 1107
Spinal shock, 1040
Spinal stenosis, congenital, 313
SPINK1  gene, 1029
Spinosad, 538, 539
Spirocerca lupi,  467, 1168
Spirometra,  1317, 1523
liver, 114
for atrioventricular valvular stenosis, 158
for cardiomyopathy, 233, 236
for pulmonic stenosis, 1154
Spitz. See also  Finnish spitz
gestational diabetes mellitus, 561

Index  1639
Splenic hemangiosarcoma , 598–599
Splenic hyperplasia, 1279
Splenic torsion , 1278
Splenitis, 1279
Splenomegaly , 1279–1280
Spondylosis deformans , 1281
Spontaneous chronic corneal epithelial 
defects (SCCED), 798, 799
Sporotrichosis , 1282
Springer spaniel. See also  English springer 
spaniel; Welsh springer spaniel
episodic muscle hypertonicity, 946
Squamous cell carcinoma , 1283–1291
digit, 1283
ear, 1284
gingiva, 1285
lung, 1286
nasal and paranasal sinuses, 1287
nasal planum, 1288
skin, 378, 384, 1289
tongue, 1290
tonsil, 1291
Squamous cell carcinoma in situ
alopecia, 65, 66
multicentric. See Multicentric 
squamous cell carcinoma in situ
SRY gene, 1238
SSRI. See Selective serotonin reuptake 
Staffordshire bull terrier. See also  
American Staffordshire terrier
Standard poodle
insulinoma, 776, 1107
sebaceous adenitis, 67, 376, 1224
vomiting, 1426Staphylococcal infections , 1292–1293
Staphylococcus
hypersensitivity blepharitis,  
182, 183
methicillin‐resistant, 909, 1164, 1292, 
1293
Staphylococcus aureus,  1292
Staphylococcus aureus  bacterin, 183
Staphylococcus pseudintermedius,  1162, 
1163, 1292
Staphylococcus schleiferi,  1164
Startle disease, 907
Status epilepticus , 1225–1229
defined, 1473
Status‐related aggression, in cats, 53
Stealing, by dogs , 1361–1362
Steatitis , 1033
Steinerma carpocapsae,  539
Stem cell therapy, 649
Stereotypies, 306
Sterile eosinophilic pustulosis,  
385, 386
Sterile nodular dermatoses , 382–383
Steroid myopathy, 941, 942
Steroid‐responsive meningitis‐arteritis, 
in dogs , 1294
Steroids. See Corticosteroids; 
Mineralocorticoids
Stertor , 1295–1296
Stevens‐Johnson syndrome, 350
Stomach tumors
Stomatitis , 1297–1298
feline, 519–520
Stool softeners
Storage pool diseases, 1327
Strabismus , 1001–1002
Strangles. See Puppy strangles
Stranguria , 430–431
Streptococcal infections , 1299
Streptococcus equi  subsp. zooepidemicus,  
215
Streptomycin, 412
Streptozocin, 568, 777
Striatin gene, 226, 227, 232, 1415
Stridor , 1295–1296
Stroke, 249–250
Strongyloides stercoralis , 1523
Strontium‐90 plesiotherapy, 165, 1288
Struvite crystalluria, 348, 349
Struvite urethral plugs, feline, 1379Struvite urolithiasis , 1379–1382
in cats, 1379–1380
in dogs, 1381–1382
Stupor , 1300–1301
Subaortic stenosis, 106–107
Subarachnoid cysts , 1302–1303
Subcorneal pustular dermatosis, 385, 386
Subinvolution of placental sites , 1304
Sublingual mucositis, 1297
Sublingual sialocele, 1214, 1215
Submissive urination in dogs , 662, 
1305
Succimer, 815, 1451
Sucralfate
liver, 114
191
204
225
for esophagitis, 465, 468, 470
553, 890
Sudden acquired retinal degeneration 
syndrome (SARDS), 184, 185, 
1193, 1194

1640  Index  
Sudden death (SD)
in aortic stenosis, 106, 107
cardiomyopathy, 226, 227
in cardiac glycoside plant 
in ventricular premature complexes, 
1410
in ventricular tachycardia, 1415, 1417
Sudden death in German shepherds , 
1404
Sulfadiazine, 1347
Sulfadiazine/trimethoprim. See 
T rimethoprim‐sulfa
Sulfadimethoxine, 214, 294, 509
Sulfasalazine (sulfapyridine‐mesalamine)
for subcorneal pustular dermatosis, 
386
Sulfonamides (sulfa drugs)
thyroid function and, 748
Sulfonylureas, 398
Sulfur/salicylic acid, 569
Sun exposure, alopecia, 65
Sun‐induced dermatoses , 384
Superficial necrolytic dermatitis 
(necrolytic migratory 
erythema) , 1306. See also  
Hepatocutaneous syndrome
in glucagonoma, 568–569
Supracollicular fluid accumulation 
(SFA), 1177
Supraspinatus tendon problems, 1247, 
1248, 1249
Supraventricular tachycardia , 1307–1308
Suprelorin, 1018
Sussex spaniel, pyruvate dehydrogenase 
phosphatase I deficiency, 948
Sweat gland adenocarcinoma , 38
Swedish Lapland
Swedish Lapphund, Pompe’s disease, 573
Swedish vallhund, spinal dysraphism, 
1276
Sweet birch oil, 472, 1457
Swimmer syndrome, 1052
Swiss cheese plant, 1455
Swollen hock syndrome. See Shar‐pei 
Sydney silky terrier, lysosomal storage 
Symblepharon, 319–320, 1325
Syncope , 1309–1310
Synechia, posterior, 92Syngonium  spp., 775
Synovial cell sarcoma , 1311
Synovial fluid analysis , 1479–1482
Syntocinon. See Oxytocin
Syringomyelia , 1312–1314
Systemic arterial hypertension , 706–708
Systemic histiocytosis (SH), 650, 651
Systemic lupus erythematosus (SLE) , 
845–846
pustules/vesicles, 385, 386
Systolic anterior motion , 1315–1316
T
T‐Relief, 1472
T3. See T riiodothyronine
T4. See Thyroxine
Tachypnea , 1036–1038
Tacrolimus
Tadalafil, 705
T aenia pisiformis,  1317
T aenia  spp., 1523
T aenia taeniaeformis,  1317
Tamoxifen, 868
Tamsulosin, 1366, 1367
Tapeworms , 1317
Tar shampoos, 377
Tarui disease. See Phosphofructokinase 
Taurine
233, 240
Taurine deficiency, 239–240
dilated cardiomyopathy, 229, 232, 
239–240
retinal degeneration, 1193, 1194
Tea tree oil, 472, 1457
Teacup poodle, status epilepticus, 1227
Tears
artificial, 319, 322, 449, 800
deficiencies, 322
overproduction, 456–457Teeth. See Tooth/teeth
Telangiectasia, renal, 308, 309
Telmisartan
for ascites, 702
for ductal plate malformation, 417
Telogen defluxion, 67, 69
Telogen effluvium, 65
Temozolomide, 129
Temperature, Fahrenheit to Celsius 
conversion table, 1569
T emporomandibular joint disorders , 
1318
Tenterfield terrier, congenital 
Tepoxalin
Teratozoospermia, 1273
Terbutaline
for tocolysis, 3, 1126
T ermination of pregnancy , 6–7
Terramycin. See Oxytetracycline
Terriers. See also specific types of terrier
granulomatous meningoencephalitis, 
442

Index  1641
pulmonary hypertension, 704
Territorial aggression
in cats, 53, 56
Testicles
disorders of development, 1238
undescended, 346
T esticular degeneration and 
hypoplasia , 1319
Testicular disorders of sexual 
T esticular torsion (torsion of spermatic 
cord) , 1345
T esticular tumors
interstitial cell tumor, 779
seminoma, 1230
Testing protocols and procedures, 
1475–1568
Testosterone
serum or plasma, 1445
T etanus , 1320–1321
Tetanus antitoxin, 1320
Tetracycline
for rickettsial disease, 1066
1205
Tetrahydrocannabinol (THC) toxicosis, 
869
Tetrahydrozoline toxicosis, 759
T etralogy of Fallot , 1322Tetramisole, 993
Tetraparesis, 1040
Tetraplegia, 1040
L‐Theanine (Anxitane)
48, 60
for fears, phobias, and anxieties, 495, 
497
for kitten behavior problems, 802, 804
1158
1334
Theileria (Babesia) vulpes,  161
Theobromine toxicosis, 260–261, 1458
Theophylline
for heartworm disease, 586
Thiamine
for seizures, 1226
Thioctic acid, 1458
Thiol‐containing drugs, for cystine 
urolithiasis, 1376–1377
Third eyelid
everted or scrolled cartilage of, 1323
neoplasia, 1323
prolapsed gland of, 1127
protrusion, 1323–1324
Thoracic lymphangiectasia, 277
Thoracocentesis and fluid analysis , 
1550–1552
for pleural effusion, 1082–1083
Thoracolumbar intervertebral disc 
disease , 784–787
Thoracostomy, tube. See Chest tube 
placement
Thorn apple, 1456
Thrombocytopathies , 1325–1326
petechiae, ecchymosis, bruising, 1072Thrombocytopenia , 1327–1329
petechiae, ecchymosis, and bruising 
in, 1072–1073
primary immune‐mediated, 1331–1332
in pseudomacrothrombocytopenia, 
1145
Thrombocytosis , 1333–1334
in hyperadrenocorticism (canine), 668
Thrombolytic therapy
1152
Thrombophilia (hypercoagulability) , 
677
Thrombospondin‐2  gene, 194
Thunder Cap, 493
ThunderShirt, 493
Thunderstorm phobia , 1333–1334
Thymoma , 1335
associated exfoliative dermatitis, feline, 
65, 1043
Thyroid adenocarcinoma (dogs) , 40–41
Thyroid atrophy, idiopathic, 747, 749
Thyroid function tests, 709, 748
Thyroid‐stimulating hormone (TSH; 
thyrotropin)
endogenous serum, 748
stimulation test, 748, 1444
Thyroiditis, lymphocytic, 747, 749
Thyrotropin. See Thyroid‐stimulating 
hormone
Thyrotropin‐releasing hormone (TRH) 
Thyroxine (T4). See also  Levothyroxine
serum, 748, 1445
Tibetan mastiff, hypertrophic 
Tibetan spaniel
639
hyperoxaluria, 308
Tibetan terrier
lysosomal storage disease, 689
Ticarcillin

1642  Index  
Ticarcillin–clavulanate, 299
Tick antitoxin hyperimmune serum, 1337
Tick bite paralysis , 1336–1337
Ticks and tick control , 1338–1339
Tiletamine‐zolazepam, 491, 493
Timolol, 273, 565, 718
Tiopronin, 971
Tissue plasminogen activator (TPA), 
109, 677
T oad venom toxicosis , 1340
Tobacco plant, 1456
Toceranib phosphate
for anal sac adenocarcinoma, 29–30
for gastrointestinal stromal tumor, 
822, 823
for hepatocellular carcinoma, 633
for lung adenocarcinoma, 31
for nasal adenocarcinoma, 32, 33
1286, 1287, 1290, 1291
Tocolytic therapy, 3, 1126
α‐Tocopherol. See Vitamin E
Toileting behavior, in cats, 657, 658, 659
Tolterodine, 505, 1380
Toltrazuril, 294
Tolvaptan, 615, 702, 1105
T ongue, squamous cell carcinoma , 1290
Tonkinese cat, blood type, 1499
T onsillar squamous cell carcinoma , 
1291
Tonsillitis, 1297
T ooth/teeth
abnormal formation/structure, 1342
dental caries, 364–365
discolored, 409–410
enamel hypoplasia/hypocalcification, 
441
feline alveolar osteitis, 498
fractures, 1353–1354
luxation injuries, 1353–1354
malocclusions, 862–863
missing, 1341
odontogenic tumors, 988–989
persistent deciduous, 359
resorption, feline, 522–523
root abscess (apical abscess), 
1343–1344
traumatic injuries, 1353–1354
Topiramate, 455, 503, 1313Torsemide
for atrioventricular valvular stenosis, 
157
953
T orsion of spermatic cord , 1345
Tortoiseshell cat, 1238, 1319
Towels, for patient handling, 490, 493
Toxascaris leonina,  1523
T oxemia, pregnancy , 1125
Toxic epidermal necrolysis (TEN), 350
Toxic home and garden hazards, 
1452–1464
Toxicity. See Intoxication
Toxocara canis,  1190–1191, 1212, 1523
Toxocara cati,  1190–1191, 1212, 1523
Toxoplasma gondii,  326, 1190–1191, 
1346, 1523
T oxoplasmosis , 1346–1347
Toy fox terrier, congenital 
Toy poodle
anemia, 89
fiber‐responsive large bowel diarrhea, 
528
442
Tracheal collapse , 1348–1349
Tracheal perforation , 810–811
Tracheal wash , 1553–1554
T raction alopecia, 65, 67
T ramadol
for paralysis, 1041for rodenticide toxicosis, 1211
T ranexamic acid, 288, 1244, 1328
Transfusion reactions , 186
T ransfusion therapy. See also  Fluid 
therapy
for anemia of chronic kidney 
disease, 80
blood typing, 1498–1500
crossmatch, 1512–1513
for iron‐deficiency anemia, 86
for nonregenerative anemia, 88
for regenerative anemia, 91
for thrombocytopenia, 1072,  
1327–1328, 1329
T ransient ischemic attack, 249
Transitional cell carcinoma (TCC) , 
1350–1351
Transmissible venereal tumor , 1352
T ranstracheal wash (TTW), 1553, 1554
T ransudates, 1527, 1528, 1529
T rapped neutrophil syndrome (TNS), 
354, 978
T raumatic brain injury, 192–193
Traumatic dentoalveolar injuries , 
1353–1354
T ravel‐related anxiety, 220–222
T ravoprost, 565
T razodone
1334
for vestibular disease, 1422
Tremor/shaker syndrome, 
Tremorgenic mycotoxicosis , 927
Tremors , 1355–1356
idiopathic head, 585
T retinoin, 14
TRH stimulation test, 1444
for eosinophilic granuloma complex, 
452Ticarcillin ( cont’d )

Index  1643
Trichiasis , 482
T richoblastoma, 578
T richoepithelioma, 578
T richolemmoma, 578
Trichomoniasis , 1357
Trichuriasis , 1435
Trichuris  spp., 301, 1371, 1435
Trichuris vulpis,  1523
T ricuspid stenosis, 156–158
T ricuspid valve dysplasia (TVD), 
154–155, 156
Tricyclic antidepressant toxicosis , 
104–105
T ricyclic antidepressants (TCAs)
48, 60
495, 497
1232–1233
1334
T rientine hydrochloride, 330, 1451
T rifluridine
797, 799
Trigeminal neuritis, idiopathic , 1358
T riiodothyronine (T3). See also  
Liothyronine
reverse, 748
serum total and free, 748, 1445
suppression test, 1444
T rilostane
for hepatocellular dysplastic 
hyperplasia, 621
for hyperadrenocorticism, 667, 
for coccidiosis, 294for head tilt, 584
for nocardiosis, 980
T rimetrexate, 1084
T ris‐EDTA, 1014
Tritrichomonas blagburni (foetus),  300, 
301, 1357
T ropicamide, 827
Trypanosoma cruzi,  254, 935
L‐T ryptophan
for canine aggression, 60
TSH. See Thyroid‐stimulating hormone
T uberculosis, 922, 923
T ularemia , 1359–1360
T ulip ( Tulipa  spp.), 1456
T umil‐K. See Potassium gluconate
T urner syndrome, 1238
T urpentine toxicosis, 1074–1075, 1463
Tylenol. See Acetaminophen
Tylosin
for cryptosporidiosis, 347
481
Tylosin‐responsive diarrhea, 1262
Tyrosinase vaccine, for melanocytic 
tumors, 887, 888
Tyrosine crystals, urinary, 349
U
U‐40 insulin, 400
Ubiquinol. See Coenzyme Q10
UDCA. See Ursodeoxycholic acid
Uhl’s anomaly, 226
Ulcerative colitis, histiocytic , 303
Ulcerative dermatoses , 374–375
Ulcerative keratitis , 798–799
Ulcerative stomatitis, canine, 1297, 1298
Ulnar closure, premature distal, 96, 97Ultrasonography, point of care
abdominal, 1538–1540
pleural space and lung, 1541–1546
Ultrasound‐guided mass or organ 
aspiration , 1555–1558
Un‐united anconeal process (UAP), 
438–439
Uncinaria stenocephala,  655, 1523
Undifferentiated pleomorphic 
sarcoma , 861
Unruly behaviors in dogs , 1361–1362
Upper motor neuron (UMN) lesions, 
1040
Upper respiratory infections, feline , 
524–525
Urachal cysts, 1421
Urate crystalluria, 348, 349
Urate urolithiasis , 1383–1384
Uremia , 159–160
Uremic acidosis, 12, 13
Uremic crisis, 275
Uremic pneumonitis, 1093
Ureter, ectopic , 434
Ureteral obstruction, 665–666, 1363
Ureterolithiasis , 1363–1364. See also  
Nephrolithiasis; Urolithiasis
Urethral catheterization , 1559–1562
Urethral obstruction
functional, 1366–1367
Urethral prolapse , 1365
Urethral sphincter mechanism 
incompetence, 434, 765, 766, 
1054
Uric acid crystalluria, 348
Uridine triacetate, 1
Urinalysis overview , 1563–1564
Urinary incontinence , 765–766
pelvic bladder, 1054
Urinary protein  : creatinine ratio (UP  : C), 
1138, 1139–1140
Urinary retention, functional , 
1366–1367
Urinary tract infections (UTI) , 
838–840
struvite urolithiasis, 1379, 1381
upper (pyelonephritis), 1160–1161
Urinary tract obstruction , 1368–1369. 
See also  Urolithiasis
anuria, 991
functional, 1366
hydronephrosis, 665–666
in nephrolithiasis, 970, 971
in polypoid cystitis, 1111
in pseudo‐urolithiasis, 1378
in ureterolithiasis, 1363

1644  Index  
Urinary tract parasites , 1370–1371
Urinary tract transitional cell carcinoma, 
1350–1351
Urinary (urethral) catheterization , 
1559–1562
Urination
inappropriate—in cats, 657–660
inappropriate—in dogs, 661–662
submissive and excitement—in dogs, 
1305
Urine acidifiers
calcium oxalate urolithiasis caused by, 
1372
for struvite urolithiasis, 1380
Urine alkalinizers
for urolithiasis, 1373, 1374, 1376, 
1385
Urine discoloration, 603
brown‐colored urine, diagnostic 
algorithm, 603
Urine marking
in cats, 657, 658, 659, 870–871
in dogs, 662, 872
Urine sampling
cystocentesis, 1514–1516
Urine sediment , 1565–1568
Uroabdomen, 1477
Urolithiasis , 1372–1385. See also  
Crystalluria; Nephrolithiasis; 
calcium oxalate, 1372–1374
calcium phosphate, 1375
cystine, 1376–1377
1118
pseudo (dried blood, ossified 
material), 1378
struvite, 1379–1382
urate, 1383–1384
xanthine, 1385
Ursodeoxycholic acid (UDCA; ursodiol)
266
for cholelithiasis, 267, 268
for hepatocutaneous syndrome, 635hepatoprotective therapy, 642
Urticaria, 350
Urticaria  spp. (nettles), 1455
Uterine inertia , 1386
Uterine tumors , 1387
Uveal melanoma , 1388–1389
in cats, 1388
in dogs, 1389
Uveitis
anterior. See Anterior uveitis
hypopyon and lipid flare, 742
lens‐induced, 246
pigmentary, of golden retrievers, 100
posterior. See Chorioretinitis
Uveodermatologic syndrome , 1390
chorioretinitis, 272, 273
nasal involvement, 956
V
Vaccine‐induced sarcoma, in cats, 1270, 
1271
Vacuolar hepatopathy, glycogen‐type , 
574–576
Vaginal discharge , 1391–1392
Vaginal hyperplasia and prolapse ,  
1393
Vaginal malformations and acquired 
lesions , 1394–1395
Vaginal tumors , 1396
Vaginitis , 1397–1398
Valerian, 1458
Valium. See Diazepam
Valley fever. See Coccidioidomycosis
Vancomycin, 263
Vascular ring anomalies , 1399
Vasculitis , 1400–1403
cutaneous, 1400
epistaxis, 460
hypersensitivity, 350
systemic, 1401–1403
Vasodilators
952, 953
for systemic hypertension, 707, 708
244, 1406
for septic shock, 1246Vasopressin V2 receptor antagonists
liver, 114
for ascites, 281, 702, 1116
Vasovagal syncope, 1309, 1310
VenomVet, 1267
Venous blood collection, 1490
Ventilatory support
Ventricular arrhythmias/sudden death 
in German shepherds , 1404
Ventricular fibrillation , 1405–1406
Ventricular pre‐excitation , 1407–1408
Ventricular premature complexes 
(VPCs) , 1409–1410
Ventricular septal defect (VSD) , 
1411–1412
Ventricular standstill (asystole) , 
1413–1414
Ventricular tachycardia , 1415–1418
Ventriculophasic sinus arrhythmia, 1255
Verapamil, 1308
Versed. See Midazolam
Vertebral column trauma , 1419–1420. 
See also  Spinal cord injury
Vertebral malformations, congenital , 
313–314
Vesicles, 385
Vesicourachal diverticula , 1421
Vesiculopustular dermatoses , 385–386
Vestibular disease , 1422–1425
in geriatric dogs, 1422–1423
head tilt, 583, 584
idiopathic feline, 1424–1425
nystagmus, 984, 985
Vestibulovaginal stenosis, 1394, 1395
Vetalog. See T riamcinolone
Veterinarians, resources for, 1571–1572
Veterinary visits, fear and aggression 
in, 490–493
in cats, 490–491
in dogs, 492–493
Vetoryl. See T rilostane
Vetsulin (porcine lente insulin), 400
Victorian bulldog, spinal dysraphism, 
1276
Vidarabine, 320
Vinblastine, 855, 875, 1351
Vincristine
for hemangiosarcoma, 594, 596, 599
thrombocytopenia, 1328, 1330
for transmissible venereal tumor, 1352
Vindesine, 31

Index  1645
Vinorelbine, 31, 1286
Viral canine hepatitis , 628–629
Viral dermatoses , 387
Viral plaques, canine pigmented, 1039
Vitamin A, 380. See also  Isotretinoin; 
Retinoids
Vitamin A‐responsive dermatosis, 376
Vitamin B complex. See B‐complex 
vitamins
Vitamin B1. See Thiamine
Vitamin B2 (riboflavin), 949
Vitamin B6. See Pyridoxine
Vitamin B12. See Cobalamin
Vitamin C. See Ascorbic acid
Vitamin D. See also  Calcitriol; 
Dihydrotachysterol; 
Ergocalciferol
deficiency, 694, 724
excess dietary intake, 522
toxicosis, 672, 1209–1210
Vitamin D‐dependent rickets, 724, 725
Vitamin E
266
deficiency, 1193
for discoid lupus erythematosus, 844
481
for precancerous ear tumors, 1284
Vitamin K deficiency, 288
Vitamin K1, 1451
265, 266for cholelithiasis, 268
for hemothorax, 606
for rodenticide toxicosis, 1207, 1211
Vitamin supplements
Vitiligo, 372, 956
Vizsla
Vocalization, excessive , 476–477
Vogt–Koyanagi–Harada syndrome 
(VKH). See Uveodermatologic 
syndrome
Vomiting
acute, 27–28
bilious, 179
chronic, 1426–1428
Von Gierke’s disease, 573
Von Meyenberg’s complexes, 416, 417
Von Willebrand disease (vWD) , 
1429–1430
epistaxis, 459, 460
petechiae, ecchymosis, bruising, 1072
Voriconazole, 123, 125, 1091
Vyvanse. See Amphetamine toxicosis
W
Wachtelhund
phosphofructokinase (PFK) deficiency, 
573, 1078
Waking at night , 476–477
Walker hound
amyloidosis, 74
1393, 1394Warbles, 351
Warfarin
for aortic thromboembolism,  
109, 110
1152
toxicosis, 1206–1207
Warming
for hypothermia, 746
Water deprivation test, modified, 
1444–1445
Water immersion accidents, 415
Weakness, exercise‐induced, in 
Weight loss , 1431–1433
Weight to body surface area conversion 
table, 1569
Weight‐unit conversion factors, 1570
Weimaraner
acne, 15
spinal dysraphism, 313, 1276, 1277
steroid‐responsive meningitis‐ 
arteritis, 894
Wells‐like syndrome, 350
Welsh corgi. See also  Cardigan 
Welsh corgi; Pembroke 
Welsh corgi
Welsh springer spaniel, glaucoma, 564

1646  Index  
West Highland white terrier
bronchiectasis, 198
interstitial pneumonia, 1092–1093
polycystic kidney disease, 308, 1188
West Nile virus infection , 1434
Wheaten terrier. See Soft‐coated wheaten 
terrier
WhelpWise™ system, 429
Whippet
lymphedema, 853
thyroid hormone levels, 748Whipworms , 1435
White cats, deafness, 357
White shaker syndrome. See 
tremor syndrome
White Swiss dog, mucopolysaccharidosis, 
908
Winter cherry, 1454
Wintergreen extract, 1458
Wintergreen oil, 472, 1457
Wirehaired dachshund
Wirehaired fox terrier
cerebellar disease, 130, 689
Wisteria ( Wisteria  spp.), 1456
Wobbler syndrome , 252–253
Wolbachia,  586, 588
Wolff–Parkinson–White (WPW) 
syndrome , 1407–1408
Wolfhound. See Irish wolfhound
Workplace safety, 1572
X
X‐linked hereditary muscular 
dystrophy , 947
X‐linked severe combined 
Xanax. See Alprazolam
Xanthine crystalluria, 348
Xanthine urolithiasis , 1385
Xanthinuria, 308, 349, 1385
Xanthoma, cutaneous, 382, 383
Xeromycteria, 958, 959
XO syndrome, 1238
Xoloitzcuintli, eclampsia, 433
XX disorders of sexual development, 
1238
XXX syndrome, 1238
XXY syndrome, 1238
XY disorders of sexual development, 
1238
Xylazine
for poisoning, 1098
Xylitol, 1436, 1458
Xylitol toxicosis , 1436
Xylometazoline toxicosis, 759Y
Yellow flag (iris), 1454
Yellow jessamine, 1456
Yellow oxeye, 1453
Yersinia pestis,  1080
Ylang ylang oil, 472, 1457
Yohimbine, 1451
for amitraz toxicosis, 363
toxicity, 1457
Yorkshire terrier
639, 640
melanoderma with alopecia, 67
849, 1136
1372, 1383
Yucca schidigera,  537
Yugoslavian shepherd, lysosomal storage 
disease, 689
Yunnan baiyao
for hemangiosarcoma, 594, 597, 599
for nasal adenocarcinoma, 33

Index  1647
Z
Zaleplon toxicosis, 169
Zamia floridana,  1213
Zantedeschia  spp., 775
Zeniquin. See Marbofloxacin
Zidovudine, 507, 515
Zinc
330, 331
for flatulence, 537for glucagonoma, 569
for halitosis, 579
1306
Zinc‐responsive dermatosis (zinc 
deficiency), 372–373, 376
Zinc toxicosis , 1437
Zoledronate, 29, 204
Zolpidem toxicosis, 169Zonisamide
for genetic epilepsy in dogs,  
454–455
Zygomatic mucocele/sialocele, 1002, 
1214, 1215
Zylkene. See Alpha‐casozepine

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