Table Of ContentPATHOLOGIC BASIS
VETERINARY
of
DISEASE
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SIXTH EDITION
PATHOLOGIC BASIS
VETERINARY
of
DISEASE
James F. Zachary, DVM, PhD, DACVP
Professor Emeritus of Veterinary Pathology
Department of Pathobiology
College of Veterinary Medicine
University of Illinois
Urbana, Illinois
3251 Riverport Lane
St. Louis, Missouri 63043
PATHOLOGIC BASIS OF VETERINARY DISEASE, SIXTH EDITION ISBN: 978-0-323-35775-3
Copyright © 2017 by Elsevier, Inc. All rights reserved.
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Notices
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Previous editions copyrighted 2012, 2007, 2001, 1995 and 1988.
Library of Congress Cataloging-in-Publication Data
Names: Zachary, James F., editor.
Title: Pathologic basis of veterinary disease/ [edited by] James F. Zachary.
Description: Sixth edition. | St. Louis, Missouri : Elsevier, [2017] |
Includes index.
Identifiers: LCCN 2016021411 | ISBN 9780323357753 (hardcover: alk. paper)
Subjects: | MESH: Animal Diseases–pathology | Animals, Domestic
Classification: LCC SF769 | NLM SF 769 | DDC 636.089/607–dc23 LC record available at
https://lccn.loc.gov/2016021411
Content Strategy Director: Penny Rudolph
Content Development Manager: Jolynn Gower
Associate Content Development Specialist: Laura Klein
Publishing Services Manager: Julie Eddy
Senior Project Manager: David Stein
Design Direction: Amy Buxton
Medical Illustrator: Theodore G. Huff
Medical Illustrator: Robert Britton
Cover Illustration: Giovanni Rimasti
Printed in China
Last digit is the print number: 9 8 7 6 5 4 3 2 1
Preface ix
inflammation characterized by accumulations of lymphocytes, mac-
In Conclusion
rophages, neutrophils, eosinophils, and a few multinucleated giant
cells occurs in perivascular areas throughout the neuropil and leads No greater impact can be made on students in their veterinary
to necrosis of both white and gray matter. Edema due to vascular education than by teachers, who are willing to share their expertise
injury accompanied by necrosis and hemorrhage can be quite promi- and knowledge with them. We hope the sixth edition of Pathologic
nent adjacent to blood vessels. Gross lesions are more common in Basis of Veterinary Disease and its mechanistic approach to disease
the spinal cord, particularly the cervical and lumbar intumescences, will assist in this process, cultivate student interest in and under-
than in the brain and appear grossly as regions of hemorrhage and standing of disease pathogeneses, and perhaps transform the way
malacia. In the brain, lesions are most commonly seen in the pathology is taught in veterinary curricula.
brainstem. James F. Zachary
Contributors
Mark R. Ackermann, DVM, PhD, DACVP John M. Cullen, VMD, PhD, DACVP, FIATP Ann M. Hargis, DVM, MS, DACVP
Professor, Department of Veterinary Professor Affiliate Associate Professor
Pathology Population Health and Pathobiology Department of Comparative Medicine
Iowa State University North Carolina State University College of University of Washington
Ames, Iowa Veterinary Medicine School of Medicine
Inflammation and Healing Raleigh, North Carolina Seattle, Washington;
Hepatobiliary System and Exocrine Pancreas Owner
Katie M. Boes, DVM, MS, DACVP Dermato Diagnostics
Clinical Assistant Professor Amy C. Durham, MS, VMD, DACVP Edmonds, Washington
Department of Biomedical Sciences and Assistant Professor The Integument
Pathobiology Department of Pathobiology
Virginia-Maryland Regional College of University of Pennsylvania Donna F. Kusewitt, DVM, PhD, DACVP
Veterinary Medicine School of Veterinary Medicine Research Professor
Virginia Polytechnic Institute and State Philadelphia, Pennsylvania Department of Pathology
University Bone Marrow, Blood Cells, and the Lymphoid/ School of Medicine
Blacksburg, Virginia Lymphatic System University of New Mexico Health Sciences
Bone Marrow, Blood Cells, and the Lymphoid/ Center
Lymphatic System Robert A. Foster, BVSc, PhD, MANZCVS, Albuquerque, New Mexico
DACVP Neoplasia and Tumor Biology
Erin M. Brannick, DVM, MS, DACVP Professor
Assistant Professor Department of Pathobiology Philippe Labelle, DVM, DACVP
Department of Animal and Food Sciences Ontario Veterinary College Adjunct Professor
University of Delaware University of Guelph Department of Pathobiology
Newark, Delaware Guelph, Ontario, Canada University of Illinois
Neoplasia and Tumor Biology Female Reproductive System and Mammae Urbana, Illinois;
Male Reproductive System Anatomic Pathologist
Melanie A. Breshears, DVM, PhD, DACVP Antech Diagnostics
Associate Professor Arnon Gal, DVM, PhD, DACVIM, DACVP Lake Success, New York
Veterinary Pathobiology Senior Lecturer in Small Animal Internal
The Eye
Oklahoma State University Medicine
Stillwater, Oklahoma Institute of Veterinary, Animal and Alfonso López, MVZ, MSc, PhD
The Urinary System Biomedical Services Professor Emeritus
Massey University Department of Pathology and Microbiology
Danielle L. Brown, DVM, DACVP, DABT Palmerston North, New Zealand Atlantic Veterinary College
Charles River Laboratories Cardiovascular System and Lymphatic Vessels University of Prince Edward Island
Head, Specialty Pathology Services Charlottetown, Prince Edward Island,
Durham, North Carolina Howard B. Gelberg, DVM, PhD, DACVP Canada
Hepatobiliary System and Exocrine Pancreas Professor Emeritus of Pathology Respiratory System, Mediastinum, and Pleurae
Department of Biomedical Sciences
Cathy S. Carlson, DVM, PhD, DACVP College of Veterinary Medicine Shannon A. Martinson, DVM, MVSc, DACVP
Professor Oregon State University Assistant Professor
Veterinary Population Medicine Corvallis, Oregon; Department of Pathology and Microbiology
University of Minnesota Professor Emeritus of Pathology Atlantic Veterinary College
Saint Paul, Minnesota Veterinary Diagnostic Laboratory University of Prince Edward Island
Bones, Joints, Tendons, and Ligaments College of Veterinary Medicine Charlottetown, Prince Edward Island,
Oregon State University Canada
Anthony W. Confer, DVM, MS, PhD, DACVP Corvallis, Oregon Respiratory System, Mediastinum, and Pleurae
Regents Professor
Alimentary System and the Peritoneum, Omentum,
Endowed Chair of Food Animal Research
Mesentery, and Peritoneal Cavity
Veterinary Pathobiology
Oklahoma State University
Stillwater, Oklahoma
The Urinary System
v
vi Contributors
M. Donald McGavin, MVSc, PhD, FACVSc, Derek A. Mosier, DVM, PhD, DACVP Paul W. Snyder, DVM, PhD, DACVP, Fellow
DACVP Professor IATP
Professor Emeritus of Veterinary Pathology Diagnostic Medicine/Pathobiology Senior Pathologist
Department of Pathobiology Kansas State University Experimental Pathology Laboratories, Inc.
College of Veterinary Medicine Manhattan, Kansas West Lafayette, Indiana
University of Tennessee Vascular Disorders and Thrombosis Diseases of Immunity
Knoxville, Tennessee
Photographic Techniques in Veterinary Pathology Sherry Myers, DVM, MVetSc, DACVP Beth A. Valentine, DVM, PhD, DACVP
Adjunct Professor Professor
Andrew D. Miller, DVM, DACVP Veterinary Pathology Department of Biomedical Sciences
Assistant Professor Western College of Veterinary Medicine Oregon State University
Department of Biomedical Sciences, Section Saskatoon, Saskatchewan, Canada; Corvallis, Oregon
of Anatomic Pathology Diagnostic Pathologist Skeletal Muscle
Cornell University College of Veterinary Prairie Diagnostic Services Inc.
Medicine Saskatoon, Saskatchewan, Canada Arnaud J. Van Wettere, DVM, MS, PhD,
Ithaca, New York The Integument DACVP
Nervous System Assistant Professor
Kimberly M. Newkirk, DVM, PhD, DACVP Department of Animal, Dairy & Veterinary
Lisa M. Miller, DVM, PhD, DACVP, MEd Associate Professor Sciences
Professor of Anatomic Pathology (retired, Department of Biomedical and Diagnostic School of Veterinary Medicine
adjunct) Sciences Utah State University
Department of Pathology and Microbiology College of Veterinary Medicine Logan, Utah
Atlantic Veterinary College University of Tennessee Hepatobiliary System and Exocrine Pancreas
Charlottetown, Prince Edward Island, Knoxville, Tennessee
Canada Neoplasia and Tumor Biology James F. Zachary, DVM, PhD, DACVP
Cardiovascular System and Lymphatic Vessels Professor Emeritus of Veterinary Pathology
Bradley L. Njaa, DVM, MVSc, DACVP Department of Pathobiology
Margaret A. Miller, DVM, PhD, DACVP Associate Professor College of Veterinary Medicine
Professor Oklahoma Animal Disease Diagnostic University of Illinois
Department of Comparative Pathobiology Laboratory Urbana, Illinois
Purdue University Center for Veterinary Health Sciences Mechanisms and Morphology of Cellular Injury,
West Lafayette, Indiana; Oklahoma State University Adaptation, and Death
Pathologist Stillwater, Oklahoma Mechanisms of Microbial Infections
Indiana Animal Disease Diagnostic The Ear Nervous System
Laboratory
Purdue University Erik J. Olson, DVM, PhD, DACVP
West Lafayette, Indiana Associate Professor
Mechanisms and Morphology of Cellular Injury, Department of Veterinary Population
Adaptation, and Death Medicine
Endocrine System College of Veterinary Medicine
University of Minnesota
St. Paul, Minnesota
Bones, Joints, Tendons, and Ligaments
Preface
The sixth edition of Pathologic Basis of Veterinary Disease continues Lastly, terminology in veterinary pathology continues to evolve
the objectives of the fourth and fifth editions in keeping students with each new edition. In this edition, students will encounter in
up to date on the latest information concerning the pathogeneses each chapter the use of different terms such as postmortem examina-
of existing, new, and reemerging veterinary diseases. This edition tion, necropsy, and autopsy (syn: necropsy) to describe methods used
has been revised and updated using the philosophy of earlier edi- to examine tissues and organ systems. Although these terms are
tions, “to explain pathology and its lesions in the context of under- synonymous, this inconstancy reflects an ongoing discussion within
standing disease in a chronological sequence of events from both the profession. There are strong opinions supporting each term and
the morphologic and mechanistic perspectives with an emphasis on the proper terminology to use will likely take several editions to sort
responses of cells, tissues, and organs to injury.” itself out.
The textbook is divided into two sections: Section 1, General
Pathology, and Section 2, Pathology of Organ Systems. General Pathol-
ogy describes the underlying causes and mechanisms of cell and
Acknowledgments
tissue injury and the resulting responses to injury (i.e., disease).
Subject matter is divided into six chapters focusing on key concepts The success of the fourth and fifth editions of Pathologic Basis of
in the areas of cellular adaptations (degenerative, regenerative, or Veterinary Disease is a direct result of the substantive and sustained
restorative) and cell death, vascular disorders, inflammation, mecha- contributions made by a group of “educators” who, on a daily
nisms of infectious diseases, disorders of immunity, and neoplasia. basis, succeed in transforming voluminous and challenging subject
Pathology of Organ Systems is the study of diseases that occur in matter into understandable and meaningful concepts and then
specific tissues, organs, and organ systems. The material is divided present them to students in a useful and “life-long learning format.”
among 15 chapters that cover disease and disease pathogeneses These pathologists are dedicated to “student learning” and convey
within each organ system. fundamental concepts about disease and disease processes and the
dynamic and ever-changing discipline of veterinary pathology in
an exciting, integrated, and well-organized manner. Additionally,
New to This Edition
they set the bar for excellence and establish the foundation for a
All 21 chapters in the sixth edition have been updated and revised; student’s clinical years and postprofessional school opportunities
10 of the chapters have been extensively rewritten and are a reflec- in veterinary medicine–related careers. These “teachers” are also
tion of the efforts of contributors new to the sixth edition. Nearly internationally renowned veterinary pathologists who, by giving
all schematic materials have been replaced with new illustrations freely of their expertise, time, and resources to this book, inspire
tailored to the practice of veterinary medicine. In addition, each veterinary students to aim high and achieve excellence in career
chapter now has its own “Key Readings Index” to aid students in endeavors.
quickly identifying and locating information relevant to their It is with great admiration that we recognize and honor the
coursework. contributions of our colleagues in previous editions. Such contribu-
Each of the six General Pathology chapters includes new sec- tions served in most instances as the foundation materials for the
tions labeled “Essential Concepts” that concisely summarize “life- process of chapter revisions in subsequent editions.
long learning” subject matter, for example, cell death, thrombosis,
acute inflammation, portals of entry, inappropriate immune 5th Edition
responses, and metastasis. Species-specific diseases in the chapters Dr. Ronald K. Myers, Chapter 1: Cellular Adaptations, Injury, and
within Pathology of Organ Systems are described under headings Death: Morphologic, Biochemical, and Genetic Bases
of the major domestic animal affected—horses, ruminants (cattle, Dr. M. Donald McGavin, Chapter 1: Cellular Adaptations, Injury, and
sheep, and goats), pigs, dogs, and cats. Those disorders and diseases Death: Morphologic, Biochemical, and Genetic Bases
not unique to a single species (i.e., those that occur in several Dr. John F. Van Vleet, Chapter 10: Cardiovascular System and Lym-
species) are grouped under the heading “Disorders of Domestic phatic Vessels
Animals.” In the sections of these chapters covering structure, Dr. Shelley J. Newman, Chapter 11: The Urinary System
function, dysfunction/responses to injury, portals of entry/pathways Dr. Krista M.D. La Perle, Chapter 12: Endocrine System
of spread, and defense mechanisms/barrier systems, new informa- Dr. Michael M. Fry, Chapter 13: Bone Marrow, Blood Cells, and the
tion on aging has been added and the full-color schematic diagrams Lymphatic System
and photographs of lesions have been updated and replaced as Dr. M. Donald McGavin, Chapter 13: Bone Marrow, Blood Cells, and
needed to emphasize pathogeneses of disease. Additionally, sections the Lymphatic System
covering postmortem examination and evaluation procedures for Dr. M. Donald McGavin, Chapter 15: Skeletal Muscle
each organ system are included in the ExpertConsult website. The Dr. Steven E. Weisbrode, Chapter 16: Bones, Joints, Tendons, and
sixth edition also includes the separation of Chapter 20, The Ear Ligaments
and Eye into two distinct chapters, Chapter 20, The Ear, and Dr. Pamela Eve Ginn, Chapter 17: The Integument
Chapter 21, The Eye. Dr. Brian P. Wilcock, Chapter 20: The Ear and Eye
vii
viii Preface
4th Edition
from the printed book and can be found on the ExpertConsult
Dr. Laura J. Rush, Chapter 6: Neoplasia and Tumor Biology website. Also included on the site are:
Dr. Anthony W. Confer, Chapter 11: The Urinary System 1. Suggested readings for each chapter.
Dr. Roger J. Panciera, Chapter 11: The Urinary System 2. Guidelines for performing systematic necropsies and appropriate
Dr. Charles C. Capen, Chapter 12: Endocrine System sample acquisition for all organ systems.
3. A glossary of abbreviations and terms used for each chapter.
4. A listing of diseases with a real or suspected genetic basis for each
3rd Edition (as Thompson’s Special organ system in Chapter 1.
Veterinary Pathology) 5. Methods for gross specimen photography and photomicrography.
Dr. William W. Carlton, Coeditor Additionally, all of the selected readings available on the Expert-
Dr. H. J. Van Kruiningen, Chapter 1: Alimentary System Consult website are linked to original abstracts in PubMed.
Dr. Richard Dubielzeg, Chapter 1: Section on Teeth: Alimentary The printed book will direct you to the ExpertConsult website
System when there is additional information available.
Dr. N. James MacLachlan, Chapter 2: Liver, Biliary System, and Finally, it is our hope that materials provided by ExpertConsult
Exocrine Pancreas can serve as the basis for course development for instructors assigned
Dr. Victor J. Ferrans, Chapter 4: Cardiovascular System the responsibility of teaching general, organ system, and diagnostic
Dr. Gene P. Searcy, Chapter 7: The Hemopoietic System pathology in veterinary curricula and for instructors in related fields
Dr. Ralph W. Storts, Chapter 8: The Nervous System within university undergraduate and graduate curricula where the
Dr. Donald L. Montgomery, Chapter 8: The Nervous System material is appropriate for course content.
Dr. Cecil E. Doige, Chapter 10: Bone and Joints
Dr. Helen M. Acland, Chapter 12: Reproductive System: Female
Dr. Helen M. Acland, Chapter 13: Reproductive System: Male
About the Cover
Dr. James A. Render, Chapter 14: The Eye and Ear
Dr. William W. Carlton, Chapter 14: The Eye and Ear Equine protozoal encephalomyelitis, an important and usually fatal
In addition, we extend our deepest appreciation and thanks to disease of horses, is caused by the protozoan Sarcocystis neurona.
colleagues throughout the world (truly an international effort), who The merozoite, the primary central nervous system (CNS) form of
have so generously provided their illustrative materials for use in the the protozoan, is small (3 to 5 µm in length), is crescent-shaped
sixth edition. Although space limitations preclude listing them here, to round, has a well-defined nucleus, and is often arranged in aggre-
their names are cited in the figure legend credit for each illustration. gates or rosettes within the neuropil and/or within neurons and
We also extend our deepest appreciation to Drs. Barry G. Harmon, other neural cells. The disease can be characterized clinically by
Elizabeth W. Howerth, and R. Keith Harris, who in their roles as depression, behavioral changes, seizures, gait abnormalities, ataxia,
Director of Noah’s Arkive, College of Veterinary Medicine, The facial nerve paralysis, head tilt, paralysis of the tongue, urinary
University of Georgia have supported our efforts over the last 2 incontinence, dysphagia, and atrophy of masseter, temporalis, quad-
decades. We have attempted to credit each illustration to its original riceps, and/or gluteal muscles, depending on the location(s) of the
source; however, inadvertent errors will be made in assembling a lesions.
textbook of this size. Please address concerns about credits to <zach- Studies show that the opossum represents the definitive host;
[email protected]>. We will make every effort to confirm the origin however, the natural intermediate host is unknown. Various
of the photograph and correct the credit before the book goes into mammals, including horses, represent aberrant intermediate hosts.
a subsequent printing. Only the merozoite and schizont stages have been found in tissues
Lastly, we thank the wide-ranging contributions of the Elsevier within the aberrant intermediate hosts. It is unclear how the organ-
staff: Jolynn Gower, Content Development Manager; Brandi ism reaches the nervous system; however, it is speculated that fol-
Graham, Content Development Specialist; Laura Klein, Associate lowing ingestion of sporocysts present in feed contaminated by
Content Development Specialist; David Stein, Senior Project opossum feces, the organism replicates in endothelial cells of the
Manager; Lois Lasater and Dan Hays, Copy Editors; and Amy alimentary system. The developing schizonts eventually release
Buxton, Senior Book Designer. We also wish to thank our merozoites, which are carried by leukocytes, likely macrophages, to
medical artists for their patience and dedication to the art for the CNS.
the sixth edition, Theodore G. Huff & Associates, Medical and Once in the CNS, merozoite-infected leukocytes appear to inter-
Biological Illustration; Robert Britton, Medical Illustrator; and act with endothelial cells, and the merozoites escape from and enter
Giovanni Rimasti, GR Illustrations Inc. (cover illustration). We endothelial cells of the blood-brain barrier, where they develop into
are also very grateful for the guidance of Penny Rudolph, Content schizonts. Ligand-receptor interactions may determine tropism in
Strategy Director, at Elsevier. Their hard work, patience, and the CNS and which areas of the vasculature are infected. Subse-
collaboration have made the revision process manageable and quently, schizogony results in lysis of these endothelial cells and
successful. release of merozoites into the neuropil, where they infect adjacent
contiguous cells such as neurons, microglial cells, and endothelial
cells. In the neuropil, merozoites occur extracellularly in cysts and
intracellularly in neurons or macrophages. The mechanisms control-
ExpertConsult Website
ling the activation of cell lysis during schizogony are uncertain, but
An ExpertConsult website accompanies the sixth edition. This site the outcomes, tissue destruction, and release of parasitic antigens
includes all of the images from the book, plus additional materials are likely factors that initiate recruitment of inflammatory cells
that may be useful adjuncts for instructors in classroom and/or labo- from the vascular system as part of a defense mechanism. These
ratory presentations. processes injure endothelium and neuropil, leading to inflammation,
To avoid adding length and weight to the book, information of vasculitis, hemorrhage, and necrosis with the recruitment of mac-
historical value and basic clinical information have been removed rophages and activation of resident microglial cells. Severe subacute
