YOU’VE JUST PURCHASED MORE THAN A TEXTBOOK ACTIVATE THE COMPLETE LEARNING EXPERIENCE THAT COMES WITH YOUR BOOK BY REGISTERING AT http://evolve.elsevier.com/Zachary/McGavin/ Once you register, you will have access to your FREE STUDY TOOLS: • Image Collection • All images from the book, plus additional images of less common diseases • Guidelines for Performing a complete, systematic necropsy and appropriate sample acquisition for selected organ systems • References that link to PubMed • Glossary of Terms to accompany selected organ systems REGISTER TODAY! James F. Zachary, DVM, PhD Diplomate, American College of Veterinary Pathologists Professor of Veterinary Pathology Department of Pathobiology College of Veterinary Medicine University of Illinois Urbana, Illinois M. Donald McGavin, MVSc, PhD, FACVSc Diplomate, American College of Veterinary Pathologists Professor Emeritus of Veterinary Pathology Department of Pathobiology College of Veterinary Medicine University of Tennessee Knoxville, Tennessee 3251 Riverport Lane St. Louis, Missouri 63043 PATHOLOGIC BASIS OF VETERINARY DISEASE ISBN: 978-0-323-07533-6 Copyright © 2012, 2007, 2001, 1995, 1988 by Mosby, Inc., an affiliate of Elsevier Inc. No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying, recording, or any information storage and retrieval system, without permission in writing from the publisher. Details on how to seek permission, further information about the Publisher’s permissions policies and our arrangements with organizations such as the Copyright Clearance Center and the Copyright Licensing Agency, can be found at our website: www.elsevier.com/permissions. This book and the individual contributions contained in it are protected under copyright by the Publisher (other than as may be noted herein). Notices Knowledge and best practice in this field are constantly changing. As new research and experience broaden our understanding, changes in research methods, professional practices, or medical treatment may become necessary. Practitioners and researchers must always rely on their own experience and knowledge in evaluating and using any information, methods, compounds, or experiments described herein. In using such information or methods they should be mindful of their own safety and the safety of others, including parties for whom they have a professional responsibility. With respect to any drug or pharmaceutical products identified, readers are advised to check the most current information provided (i) on procedures featured or (ii) by the manufacturer of each product to be administered, to verify the recommended dose or formula, the method and duration of administration, and contraindications. It is the responsibility of practitioners, relying on their own experience and knowledge of their patients, to make diagnoses, to determine dosages and the best treatment for each individual patient, and to take all appropriate safety precautions. To the fullest extent of the law, neither the Publisher nor the authors, contributors, or editors, assume any liability for any injury and/or damage to persons or property as a matter of products liability, negligence or otherwise, or from any use or operation of any methods, products, instructions, or ideas contained in the material herein. ISBN: 978-0-323-07533-6 Publisher: Penny Rudolph Managing Editor: Shelly Stringer Publishing Services Manager: Catherine Jackson Senior Project Manager: David Stein Design Direction: Paula Catalano Medical Artist: Theodore G. Huff Working together to grow libraries in developing countries www.elsevier.com | www.bookaid.org | www.sabre.org Printed in China Last digit is the print number: 9 8 7 6 5 4 3 2 1 CONTRIBUTORS Mark R. Ackermann, DVM, PhD, DACVP Arnon Gal, DVM, MS, DACVIM (SAIM) Professor Anatomic Pathology Resident Department of Veterinary Pathology Department of Pathobiology College of Veterinary Medicine College of Veterinary Medicine Iowa State University University of Illinois Ames, Iowa Urbana, Illinois Inflammation and Healing Cardiovascular System and Lymphatic Vessels Danielle L. Brown, DVM, DACVP Howard B. Gelberg, DVM, PhD, DACVP Staff Pathologist Professor of Pathology WIL-Biotechnics Department of Biomedical Sciences Hillsborough, North Carolina College of Veterinary Medicine Hepatobiliary System and Exocrine Pancreas Oregon State University Corvallis, Oregon Cathy S. Carlson, DVM, PhD, DACVP Alimentary System and the Peritoneum, Omentum, Mesentery, and Professor Peritoneal Cavity Department of Veterinary Population Medicine Pamela Eve Ginn, DVM, DACVP College of Veterinary Medicine University of Minnesota Visiting Associate Professor St. Paul, Minnesota Department of Infectious Diseases and Pathology Bones, Joints, Tendons, and Ligaments College of Veterinary Medicine University of Florida John M. Cullen, VMD, PhD, DACVP Gainesville, Florida Professor The Integument Department of Population Health and Pathobiology Ann M. Hargis, DVM, MS, DACVP College of Veterinary Medicine North Carolina State University Owner Raleigh, North Carolina DermatoDiagnostics Hepatobiliary System and Exocrine Pancreas Edmonds, Washington Affiliate Associate Professor Robert A. Foster, BVSc, PhD, MACVSc, DACVP Department of Comparative Medicine Professor University of Washington Department of Pathobiology School of Medicine Ontario Veterinary College Seattle, Washington University of Guelph The Integument Guelph, Ontario, Canada Donna F. Kusewitt, DVM, PhD, DACVP Female Reproductive System and Mammary Gland Male Reproductive System Professor Department of Molecular Carcinogenesis, Science Park Research Michael M. Fry, DVM, MS, DACVP Division Associate Professor University of Texas M.D. Anderson Cancer Center Department of Pathobiology Smithville, Texas College of Veterinary Medicine Neoplasia and Tumor Biology University of Tennessee Knoxville, Tennessee Bone Marrow, Blood Cells, and the Lymphatic System v vi CONTRIBUTORS Krista M.D. La Perle, DVM, PhD, DACVP Bradley L. Njaa, DVM, MVSc, DACVP Associate Professor Associate Professor Director of Comparative Pathology & Mouse Phenotyping Department of Veterinary Pathobiology Shared Resource Center for Veterinary Health Sciences Department of Veterinary Biosciences Oklahoma State University College of Veterinary Medicine Stillwater, Oklahoma The Ohio State University The Ear and Eye Columbus, Ohio Paul W. Snyder, DVM, PhD, DACVP Endocrine System Professor of Veterinary Pathology Alfonso López, MVZ, MSc, PhD Comparative Pathobiology Professor of Pathology School of Veterinary Medicine Department of Pathology and Microbiology Purdue University Atlantic Veterinary College West Lafayette, Indiana University of Prince Edward Island Diseases of Immunity Charlottetown, Prince Edward Island, Canada Beth A. Valentine, DVM, PhD, DACVP Respiratory System, Mediastinum, and Pleurae Professor M. Donald McGavin, MVSc, PhD, FACVSc, DACVP Department of Biomedical Sciences Professor Emeritus of Veterinary Pathology College of Veterinary Medicine Department of Pathobiology Oregon State University College of Veterinary Medicine Corvallis, Oregon University of Tennessee Skeletal Muscle Knoxville, Tennessee John F. Van Vleet, DVM, PhD, DACVP Cellular Adaptations, Injury, and Death: Morphologic, Biochemical, and Genetic Bases Professor Emeritus of Veterinary Pathology Bone Marrow, Blood Cells, and the Lymphatic System Comparative Pathobiology Skeletal Muscle School of Veterinary Medicine Photographic Techniques in Veterinary Pathology Purdue University West Lafayette, Indiana Lisa M. Miller, DVM, PhD, DACVP, Med Cardiovascular System and Lymphatic Vessels Professor Steven E. Weisbrode, VMD, PhD, DACVP Department of Pathology and Microbiology Atlantic Veterinary College Professor Emeritus University of Prince Edward Island Department of Veterinary Biosciences Charlottetown, Prince Edward Island, Canada College of Veterinary Medicine Cardiovascular System and Lymphatic Vessels The Ohio State University Columbus, Ohio Derek A. Mosier, DVM, PhD, DACVP Bones, Joints, Tendons, and Ligaments Professor Brian P. Wilcock, DVM, PhD Department of Diagnostic Medicine/Pathobiology College of Veterinary Medicine Senior Pathologist Kansas State University Histovet Surgical Pathology Manhattan, Kansas Guelph, Ontario, Canada Vascular Disorders and Thrombosis Professor Emeritus Department of Pathobiology Ronald K. Myers, DVM, PhD, DACVP Ontario Veterinary College Professor University of Guelph Department of Veterinary Pathology Guelph, Ontario, Canada College of Veterinary Medicine The Ear and Eye Iowa State University James F. Zachary, DVM, PhD, DACVP Ames, Iowa Cellular Adaptations, Injury, and Death: Morphologic, Biochemical, Professor of Veterinary Pathology and Genetic Bases Department of Pathobiology College of Veterinary Medicine Shelley J. Newman, DVM, DVSc, DACVP University of Illinois Associate Professor Urbana, Illinois Department of Pathobiology Cellular Adaptations, Injury, and Death: Morphologic, Biochemical, College of Veterinary Medicine and Genetic Bases University of Tennessee Mechanisms of Microbial Infections Knoxville, Tennessee Nervous System The Urinary System PREFACE EVOLVE SITE Following the enthusiastic reception of the fourth edition of Patho logic Basis of Veterinary Disease both nationally and internationally, the fifth edition continues with the same philosophical approach— An enhanced Evolve site accompanies this edition. The Evolve site explaining pathology and its lesions in the context of understand- includes all of the images from the book, plus additional images and ing disease in a chronological sequence of events from both the schematic illustrations that supplement some common diseases and morphologic and mechanistic perspectives, and with an emphasis disease processes discussed in the book. These additional materials on responses of cells, tissues, and organs to injury. may be useful adjuncts for instructors in classroom and/or labora- Veterinary pathology is a dynamic discipline and since the tory presentations. fourth edition was published in 2006, there have been many new To avoid adding length and weight to the book, information of insights into the pathogeneses of existing diseases and new or historical value and basic clinical information have been removed reemerging diseases, many of which have serious economic and from the printed book and can be found on the Evolve site. Also health consequences for animals and humans. As a result, to meet included on the Evolve site are guidelines for performing a com- the growing scope of the veterinary curriculum we have added to plete, systematic necropsy and appropriate sample acquisition for the fifth edition new and revised materials on pets, livestock, and selected organ systems; a glossary of terms to accompany selected production animal health, including diseases the USDA/APHIS organ systems; and methods for gross specimen photography and and the World Organization for Animal Health (OIE) consider photomicrography. Additionally, all of the selected readings are as “Foreign Animal Diseases” or “OIE Reportable Diseases,” available on the Evolve site and are linked to original abstracts respectively. on PubMed. The book is not meant to be encyclopedic; specific diseases have The printed book will direct you to the website when there is been selected either because they are of primary importance in the additional information available. practice of veterinary medicine or because they illustrate a basic mechanism. We also hope this edition will continue to provide a ABOUT THE COVER bridge between students’ understanding of material learned in the basic sciences and the interpretation of results of physical examina- tions, differential disease diagnoses, imaging modalities, biochemi- Canine parvovirus enteritis, an important and often fatal disease of cal and molecular diagnostic methods, and therapeutic strategies dogs, is caused by a cytolytic virus that infects and kills mitotically presented in the students’ clinical years. active cells including crypt enterocytes of the small intestine. Virus in fecal matter is inhaled or ingested and then deposited on and trapped in the mucus layer of oral, nasal, and pharyngeal mucosae, NEW TO THIS EDITION where it infects mucosal macrophages or dendritic cells. These cells spread parvovirus to lymphocytes of the lamina propria of the The fifth edition of Pathologic Basis of Veterinary Disease has been mucosa, especially that of the tonsil where it infects and replicates updated and reorganized such that specific diseases are described in lymphocytes. Many of these cells subsequently lyse, allowing under the major domestic animal affected—horses, ruminants virus to escape free into the lymph, where it and infected macro- (cattle, sheep, and goats), pigs, dogs, and cats. Those disorders and phages drain to regional lymph nodes and then, via the blood vas- diseases not unique to a single species are grouped under a heading cular system, systemically to the spleen, thymus, lymph nodes, bone titled “Disorders of Domestic Animals.” We continue to describe marrow, and mucosa-associated lymphoid nodules (MALT) such disease pathogenesis based on sections covering structure, func- as Peyer’s patches of the small intestine. In Peyer’s patches, chiefly tion, portals of entry, defense mechanisms, and responses to injury, the mitotically active cells of the lymphoid follicle are infected and augmented by schematic color diagrams and full color illustrations lysed (lymphocytolysis). From Peyer’s patches, parvovirus spreads of lesions. Our hope is that this approach will be helpful to the to adjacent crypts causing enterocyte necrosis, with the result that student (and to their instructors) in their understanding of both enterocytes required to replace those lost in normal turnover of pathology and the related disciplines of microbiology, immunol- absorptive enterocytes sloughed from the tip of a villus, or from ogy, and infectious diseases. Other additions to the fifth edition destruction by the virus, are not produced. Consequently, villi in include new sections on the genetic basis of disease, diseases of the a short time are denuded of epithelium, and the primary gross ear, and diseases of ligaments and tendons and a new chapter on lesion that results is fibrinonecrotic enteritis with hemorrhage and mechanisms of microbial infections. an accompanying serositis. Necrotic crypt enterocytes slough and vii viii PREFACE release virus into the intestinal lumen and then, through diarrheic to confirm the origin of the photograph and correct the acknowl- feces, pass it into the environment. edgment before the book goes into the next printing. If no crypt enterocytes are viable, the villi will remain naked, Although we have used materials from many Elsevier books, we collapse, and fuse together; however, if some crypt enterocytes are wish to specifically acknowledge the editors of the following books still viable, they will become hyperplastic and divide rapidly to for granting use of some of their illustrative materials: re-epithelialize the denuded villi. To facilitate this process, the villi • Vinay Kumar, Abul K. Abbas, Nelson Fausto, and Jon Aster: collapse to reduce the volume of their surface area and the crypt Robbins and Cotran Pathologic Basis of Disease enterocytes replicate to produce a less specialized low cuboidal • Abraham L. Kierszenbaum: Histology and Cell Biology: an Intro enterocyte that spreads out to cover the exposed basement mem- duction to Pathology brane of the surface area. With time, these less specialized entero- • Lee-Ellen C. Copstead and Jacquelyn L. Banasik: Pathophysio cytes will be replaced by fully functioning columnar enterocytes. logy: Biological and Behavioral Perspectives Thus villus atrophy can be either a transitory stage in regeneration • Kathryn L. McCance and Sue E. Huether: Pathophysiology: the with return to normal structure and function of affected villi or a Biologic Basis for Disease in Adults and Children permanent alteration if there is complete destruction of “regenera- • Sue E. Huether and Kathryn L. McCance: Understanding tive” crypt enterocytes in that segment of the small intestine. Pathophysiology We also wish to acknowledge the contributions of the Elsevier staff: Shelly Stringer (managing editor), David Stein (senior production ACKNOWLEDGMENTS editor), and Theodore G. Huff (medical artist). We also appreciate the input of Penny Rudolph, publisher at Elsevier. Finally, we wish We wish to extend our deepest appreciation and thanks to our col- to thank our families—James Zachary to his daughters, Amanda leagues throughout the world (truly an international effort), who and Briana, and Donald McGavin to his late wife, Beverley—for have so generously provided their illustrative materials for use in their support and encouragement during this process. the fifth edition. Although space limitations preclude listing them No greater impact can be made on students in their veterinary here, their names are cited in the figure legend credit for each illus- education than by teachers, including veterinary pathologists, who tration. We also extend our deepest appreciation to Dr. Elizabeth are willing to share their expertise and knowledge with them. W. Howerth, Director of Noah’s Arkive, College of Veterinary We hope that Pathologic Basis of Veterinary Disease will aid in this Medicine, The University of Georgia for allowing us to use illus- process, foster the student’s understanding of mechanistic concepts, trations from the Arkive. We have made every attempt to properly and perhaps also alter the way that veterinary pathologists think credit each illustration to its original source; however, we recognize about teaching pathology. that inadvertent errors will be made in the process of assembling a < textbook. Please address any concerns about credits to zacharyj@ JAMES F. ZACHARY > < > illinois.edu or [email protected] . We will make every effort M. DONALD McGAVIN CONTENTS SECTION 1 GENERAL PATHOLOGY 1 CELLULAR ADAPTATIONS, INJURY, AND DEATH: MORPHOLOGIC, BIOCHEMICAL, AND GENETIC BASES, 2 Ronald K. Myers, M. Donald McGavin, and James F. Zachary Basic Terminology, 2 Types of Diagnosis, 3 Morphologic Changes and How They Are Detected and Evaluated, 3 The Normal Cell, 4 Causes of Cell Injury, 7 Reversible Cell Injury, 10 Irreversible Cell Injury and Cell Death, 13 Chronic Cell Injury and Cell Adaptation, 26 Cellular Aging, 48 Genetic Basis of Disease, 49 2 VASCULAR DISORDERS AND THROMBOSIS, 60 Derek A. Mosier Circulatory System, 60 Microcirculation, Interstitium, and Cells, 61 Fluid Distribution and Homeostasis, 61 Abnormal Fluid Distribution, 66 Hemostasis, 68 Disorders of Hemostasis: Hemorrhage and Thrombosis, 75 Normal Blood Flow, Distribution, and Perfusion, 82 Alterations in Blood Flow and Perfusion, 83 Shock, 86 3 INFLAMMATION AND HEALING, 89 Mark R. Ackermann Evolution of the Current Understanding of Inflammation, 89 Beneficial and Harmful Aspects of Inflammation, 89 Acute Inflammation, 91 Substances Inducing the Acute Inflammatory Response, 93 Fluidic (Exudative) Phase of the Acute Inflammatory Response, 95 Cellular Phase of the Acute Inflammatory Response, 96 ix
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