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PATHOLOGIC BASIS of VETERINARY DISEASE
Seventh Edition
PATHOLOGIC BASIS of VETERINARY DISEASE
JAMES F. ZACHARY , DVM, PhD, DACVP
Professor Emeritus, Veterinary Pathology
Department of Pathobiology
College of Veterinary Medicine
University of Illinois Urbana, Illinois
Elsevier
3251 Riverport Lane
St. Louis, Missouri 63043
PATHOLOGIC BASIS OF VETERINARY DISEASE, SEVENTH EDITION
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Notice
Practitioners and researchers must always rely on their own experience and knowledge in evaluating and using any information, methods, compounds or experiments described herein. Because of rapid advances in the medical sciences, in particular, independent verification of diagnoses and drug dosages should be made. To the fullest extent of the law, no responsibility is assumed by Elsevier, authors, editors or contributors 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.
Previous editions copyrighted 2017, 2012, 2007, 2001, 1995, and 1988
Library of Congress Control Number: 2021945633
Senior Content Strategist: Jennifer Catando
Senior Content Development Manager: Luke Held
Senior Content Development Specialist: Maria Broeker
Publishing Services Manager: Julie Eddy
Senior Project Manager: Rachel E. McMullen
Project Manager: Julie Mangoff
Design Direction: Amy Buxton
Cover Illustrations and Artwork: Warren Photographic Ltd. (cat image), Warren House, Albury Heath, Guildford, UK; Dr. A.R. Armstrong, College of Veterinary Medicine, University of Minnesota; Dr. M. Donald McGavin, College of Veterinary Medicine, University of Tennessee; Dr. J.F. Zachary, College of Veterinary Medicine, University of Illinois.
Printed in Canada
Mark R. Ackermann, DVM, PhD, DACVP
Professor and Director
Department of Biomedical Sciences and Oregon Veterinary Diagnostic Laboratory
Carlson College of Veterinary Medicine
Oregon State University
Corvallis, Oregon
Chapter 3 Inflammation and Healing
Alexandra R. Armstrong, DVM, DACVP
Department of Veterinary Clinical Sciences
College of Veterinary Medicine
University of Minnesota
St. Paul, Minnesota
Chapter 16 Bones, Joints, Tendons, and Ligaments
Katie M. Boes, DVM, MS, DACVP
Clinical Associate Professor, Veterinary Clinical Pathology
Department of Biomedical Sciences and Pathobiology
Virginia Polytechnic Institute and State University
Blacksburg, Virginia
Chapter 13 Bone Marrow, Blood Cells, and the Lymphoid/Lymphatic System
Erin M. Brannick, DVM, MS, DACVP
Associate Professor
Department of Animal and Food Sciences
University of Delaware
Newark, Delaware
Chapter 6 Neoplasia and Tumor Biology
Appendix A Communication, Collaboration, and Consultation in Veterinary Pathology
Danielle L. Brown, DVM, MS, DACVP, DABT
General Manager
Charles River Laboratories
Durham, North Carolina
Chapter 8 Hepatobiliary System and Exocrine Pancreas
Cathy S. Carlson, DVM, PhD, DACVP
Professor and Chair
Department of Veterinary Clinical Sciences
College of Veterinary Medicine
University of Minnesota
St. Paul, Minnesota
Chapter 16 Bones, Joints, Tendons, and Ligaments
Fernanda Castillo-Alcala, MVZ, DVSc, DACVP
Senior Lecturer in Anatomical Pathology
School of Veterinary Science
Massey University
Palmerston North, New Zealand
Chapter 10 Cardiovascular System, Pericardial Cavity, and Lymphatic Vessels
Amy C. Durham, MS, VMD, DACVP
Associate Professor, Anatomic Pathology
Department of Pathobiology
School of Veterinary Medicine
University of Pennsylvania
Philadelphia, Pennsylvania
Chapter 13 Bone Marrow, Blood Cells, and the Lymphoid/Lymphatic System
Jaclyn A. Dykstra, DVM, PhD, DACVP
Assistant Professor
Department of Veterinary Population Medicine
College of Veterinary Medicine
University of Minnesota
St. Paul, Minnesota
Chapter 16 Bones, Joints, Tendons, and Ligaments
Robert A. Foster, BVSc, PhD, MANZCVS, DACVP
Professor
Department of Pathobiology
Ontario Veterinary College
University of Guelph
Guelph, Ontario, Canada
Chapter 18 Female Reproductive System and Mammae
Chapter 19 Male Reproductive System
Arnon Gal, DVM, PhD, DACVIM, DACVP
Assistant Professor
Small Animal Internal Medicine
Department of Veterinary Clinical Medicine
University of Illinois
Urbana, Illinois
Chapter 10 Cardiovascular System, Pericardial Cavity, and Lymphatic Vessels
Contributors
Howard B. Gelberg, DVM, PhD, DACVP
Professor Emeritus of Pathology
Department of Biomedical Sciences and Veterinary Diagnostic Laboratory
Carlson College of Veterinary Medicine
Oregon State University
Corvallis, Oregon
Chapter 7 Alimentary System and the Peritoneum, Omentum, Mesentery, and Peritoneal Cavity
Philippe Labelle, DVM, DACVP
Anatomic Pathologist
Antech Diagnostics
Ottawa, Ontario
Canada
Chapter 21 The Eye
Laura V. Lane, DVM, DACVP
Veterinary Clinical Pathologist
IDEXX Laboratories, Inc.
Irvine, California
Chapter 11 The Urinary System
Keith E. Linder, DVM, PhD, DACVP
Clinical Professor of Anatomic Pathology
College of Veterinary Medicine
North Carolina State University
Raleigh, North Carolina
Chapter 17 The Integument
Alfonso López, MVZ, MSc, PhD
Professor Emeritus
Department of Pathology and Microbiology, Atlantic Veterinary College
University of Prince Edward Island
Charlottetown, Prince Edward Island
Canada
Chapter 9 Respiratory System, Thoracic Cavities, Mediastinum, and Pleurae
L. Tiffany Lyle, DVM, PhD, DACVP
Assistant Professor of Veterinary Anatomic Pathology
Department of Comparative Pathobiology
College of Veterinary Medicine
Purdue University
West Lafayette, Indiana
Chapter 1 Mechanisms and Morphology of Cellular Injury, Adaptation, and Death
Shannon A. Martinson, DVM, MVSc, DACVP
Associate Professor, Veterinary Pathology
Department of Pathology and Microbiology
Atlantic Veterinary College
University of Prince Edward Island
Charlottetown, Prince Edward Island Canada
Chapter 9 Respiratory System, Thoracic Cavities, Mediastinum, and Pleurae
M. Donald McGavin, MVSc, PhD, FACVSc, DACVP
Professor Emeritus of Veterinary Pathology
Department of Pathobiology
College of Veterinary Medicine, University of Tennessee
Knoxville, Tennessee
Appendix B Photographic Techniques in Veterinary Pathology
Appendix F General Principles of Tissue Fixation and Processing
Appendix G Fixatives and Fixation
Appendix H Fixation and Trimming of the Brain, Spinal Cord, and Nerves
Appendix I Surgical Biopsies—Procurement, Processing, and Sectioning Artifacts
Appendix J Gross Examination and Infusion Fixation of the Lung
Andrew D. Miller, DVM, DACVP
Associate Professor
Department of Biomedical Sciences, Section of Anatomic Pathology
College of Veterinary Medicine
Cornell University
Ithaca, New York
Chapter 14 Nervous System
Margaret A. Miller, DVM, PhD, DACVP Professor, Veterinary Pathology
Department of Comparative Pathobiology and Animal Disease Diagnostic Laboratory College of Veterinary Medicine
Purdue University
West Lafayette, Indiana
Introduction: Fundamentals for Understanding Veterinary Pathology
Chapter 1 Mechanisms and Morphology of Cellular Injury, Adaptation, and Death
Chapter 12 Endocrine System
Appendix E Diagnoses in Veterinary Pathology
Appendix G Fixatives and Fixation
Derek A. Mosier, DVM, PhD, DACVP
Professor Diagnostic Medicine/Pathobiology
Kansas State University
Manhattan, Kansas
Chapter 2 Vascular Disorders and Thrombosis
Kimberly M. Newkirk, DVM, PhD, DACVP Professor
Biomedical and Diagnostic Sciences
College of Veterinary Medicine
University of Tennessee
Knoxville, Tennessee
Chapter 6 Neoplasia and Tumor Biology
Shelley J. Newman, DVM, PhD, DACVP
Newman Specialty VetPath
Hicksville, New York
Appendix H Fixation and Trimming of the Brain, Spinal Cord, and Nerves
Bradley L. Njaa, DVM, MVSc, DACVP Professor
Kansas State Veterinary Diagnostic Laboratory (KSVDL)
Department of Diagnostic Medicine/ Pathobiology (DM/P)
College of Veterinary Medicine
Kansas State University
Manhattan, Kansas
Chapter 20 The Ear
Erik J. Olson, DVM, PhD, DACVP
Associate Professor
Department of Veterinary Population Medicine
College of Veterinary Medicine
University of Minnesota
St. Paul, Minnesota
Chapter 16 Bones, Joints, Tendons, and Ligaments
Brian F. Porter, DVM, DACVP
Clinical Professor
Department of Veterinary Pathobiology
College of Veterinary Medicine & Biomedical Sciences
Texas A&M University
College Station, Texas
Chapter 14 Nervous System
Christopher Premanandan, DVM, PhD, DACVP, DACT
Associate Professor—Clinical
Department of Veterinary Biosciences
College of Veterinary Medicine
The Ohio State University Columbus, Ohio
Chapter 18 Female Reproductive System and Mammae
Chapter 19 Male Reproductive System
Patrick J. Roady, DVM, MS, DACVP
Clinical Associate Professor
Veterinary Diagnostic Laboratory
College of Veterinary Medicine
University of Illinois
Urbana, Illinois
Appendix C Postmortem Examination (Autopsy) of Domestic Animal Species
Appendix D Recognition and Interpretation of Macroscopic (Gross) Lesions
Deanna M.W. Schaefer, DVM, DACVP
Associate Professor of Veterinary Clinical Pathology
Biomedical and Diagnostic Sciences
College of Veterinary Medicine
University of Tennessee
Knoxville, Tennessee
Chapter 6 Neoplasia and Tumor Biology
Paul W. Snyder, DVM, PhD, DACVP, Fellow IATP
Senior Pathologist
Experimental Pathology Laboratories, Inc.
Bonita Springs, Florida
Chapter 5 Diseases of Immunity
Sean T. Spagnoli, DVM, DACVP
Assistant Professor of Veterinary Pathology
Department of Biomedical Sciences and Veterinary Diagnostic Laboratory
Carlson College of Veterinary Medicine
Oregon State University
Corvallis, Oregon
Chapter 7 Alimentary System and the Peritoneum, Omentum, Mesentery, and Peritoneal Cavity
James B. Stanton, DVM, PhD, DACVP
Associate Professor
Department of Pathology
University of Georgia
Athens, Georgia
Chapter 4 Mechanisms of Microbial Infections
Mee-Ja M. Sula, DVM, DACVP
Clinical Associate Professor of Anatomic Pathology
Biomedical and Diagnostic Sciences
College of Veterinary Medicine
University of Tennessee
Knoxville, Tennessee
Chapter 11 The Urinary System
Beth A. Valentine, DVM, PhD, DACVP
Emeritus Professor
Department of Biomedical Sciences
Carlson College of Veterinary Medicine
Oregon State University
Corvallis, Oregon
Chapter 15
Skeletal Muscle
Monika M. Welle, Dr. med. vet., DECVP
Associate Professor
Department of Infectious Diseases and Pathobiology
Institute of Animal Pathology
Vetsuisse Faculty
Bern, Switzerland
Chapter 17 The Integument
Arnaud J. Van Wettere, DVM, MS, PhD, DACVP
Associate Professor of Veterinary Pathology Department of Animal, Dairy & Veterinary Sciences; Utah Veterinary Diagnostic Laboratory
School of Veterinary Medicine
Utah State University
Logan, Utah
Chapter 8 Hepatobiliary System and Exocrine Pancreas
James F. Zachary, DVM, PhD, DACVP
Professor Emeritus, Veterinary Pathology Department of Pathobiology
University of Illinois
Urbana, Illinois
Introduction: Fundamentals for Understanding Veterinary Pathology
Chapter 1 Mechanisms and Morphology of Cellular Injury, Adaptation, and Death
Chapter 4 Mechanisms of Microbial Infections
Appendix C Postmortem Examination (Autopsy) of Domestic Animal Species
Appendix D Recognition and Interpretation of Macroscopic (Gross) Lesions
Appendix E Diagnoses in Veterinary Pathology
Appendix F General Principles of Tissue Fixation and Processing
Appendix G Fixatives and Fixation
Appendix H Fixation and Trimming of the Brain, Spinal Cord, and Nerves
Appendix I Surgical Biopsies—Procurement, Processing, and Sectioning Artifacts
Appendix J Gross Examination and Infusion Fixation of the Lung
The seventh edition of Pathologic Basis of Veterinary Disease provides students with current information on veterinary diseases and how to understand their lesions and pathogeneses in a chronologic sequence of events from both the morphologic and mechanistic perspectives with an emphasis on the responses of cells, tissues, and organs to injury.
New to this Edition
• All 21 chapters have been revised to describe and illustrate the latest knowledge of the subject matter.
• Fourteen new contributors convey innovative ideas and insight into chapter revisions and new appendices.
• An Introduction has been added to provide readers with background information useful in understanding the concepts illustrated and discussed throughout this book.
• Pathogenesis pathways (i.e., step-by-step sequence maps of the key elements in a disease) have been introduced in Chapter 4, Mechanisms of Microbial Infections.
• All figures from the sixth edition have been reviewed and as needed, digitally edited, to improve the quality of the macroscopic (gross) photographs and photomicrographs, so key diagnostic characteristics are quickly revealed.
• Key readings indexes, essential concepts boxes, schematic diagrams, flowcharts, figures/figure legends, tables, and text boxes have been reviewed and updated.
• The cytomorphology and histomorphology of inflammatory cells and inflammatory exudates are illustrated and compared in Chapter 3, Inflammation and Healing.
• The cytomorphology and histomorphology of microbes commonly seen in the practice of veterinary medicine are illustrated and compared in Chapter 4, Mechanisms of Microbial Infections.
• The cytomorphology and histomorphology of tumors commonly seen in the practice of veterinary medicine are described, compared, and illustrated in Chapter 6, Neoplasia and Tumor Biology.
• The key cytomorphologic features of normal, benign, and malignant cells are reviewed in Chapter 6, Neoplasia and Tumor Biology.
• The procedures for collecting specimens for cytologic evaluation are discussed in Chapter 6, Neoplasia and Tumor Biology.
• The cytomorphology and histomorphology of lymphoid tumors commonly seen in dogs and cats are described, compared, and illustrated in Chapter 13, Bone Marrow, Blood Cells, and the Lymphoid/Lymphatic System.
• Cross-referencing of disorders within and between chapters and species has been simplified.
• The Key Readings Index headings have been updated in the Pathology of Organ System chapters, so where appropriate, the headings pertinent to an organ or organ system stand out in a blue, bold font making them easy to identify and use.
• Ten new “online” appendices have been added that discuss and illustrate postmortem activities and include:
• Communication, Collaboration, and Consultation in Veterinary Pathology
• Postmortem Examination (Autopsy) of Domestic Animal Species
Preface
• Recognition and Interpretation of Macroscopic (Gross) Lesions
• Diagnoses in Veterinary Pathology
• General Principles of Tissue Fixation and Processing
• Fixatives and Fixation
• Fixation and Trimming of the Brain, Spinal Cord, and Nerves
• Surgical Biopsies—Procurement, Processing, and Sectioning Artifacts
• Gross Examination and Infusion Fixation of the Lung
• Necropsy Techniques by Organ System
Acknowledgment of Contributors
We extend our deepest appreciation and thanks to the contributors of our chapters and appendices, who have so generously provided their expertise, time, and effort to complete all of the objectives for the seventh edition of Pathologic Basis of Veterinary Disease and for their support of veterinary pathology and veterinary pathologists worldwide.
It has been approximately 33 years since the first edition, titled Special Veterinary Pathology, was published in 1988. It was 661 pages in length and covered special pathology (pathology of organ systems) with photomicrographs and schematic diagrams (line drawings) printed in black and white (grayscale). Over the next decade, the second (1995) and third (2001) editions, titled Thomson’s Special Veterinary Pathology , were revised based on the existing chapter materials and grayscale figures. In preparation for the fourth edition, the editors were informed that the book could be printed in full color (cyan, magenta, yellow, and black [CMYK]). This opportunity required an evaluation of the third edition and the development of a strategy to ensure the long-term success of a book printed in full color. After extensive discussions, it was concluded that the fourth edition would need to have substantial design and figure revisions to justify using the full-color format. Revisions were based on chapter materials from the third edition, which were updated to reflect advancements occurring in the subject matter and in the methods used to teach pathology to veterinary students. Six new chapters covering general pathology were added, and existing chapters were revised and updated so all pathology of organ system chapters had a common instructional format. In addition, the processes required to identify and prepare color images and color artwork for over 2000 new illustrations used in the fourth edition were begun. Lastly, the book was retitled Pathologic Basis of Veterinary Disease, so the title more closely reflected the content and instructional philosophy of the revised book.
In August of 2006, Pathologic Basis of Veterinary Disease, fourth edition was available as the result of the dedication and efforts of contributors, editors, and Elsevier staff. Subsequently, every 5 years a similar revision strategy that has emphasized quality and clarity has been used to produce the fifth (2012) and sixth (2017) editions. We sincerely thank everyone for their contributions throughout these six editions and, in the following table, acknowledge their efforts in making this book a success as the seventh edition (2021).
Authors Editions*
Chapter Title(s)
Dr. Mark R. Ackermann 4th through 6th editions • Acute Inflammation (4th Edition) • Chronic Inflammation and Wound Healing (4th Edition) • Inflammation and Healing (5th and 6th Editions)
Dr. Helen M. Acland 1st through 3rd editions • Male Reproductive System (1st Edition)
• Female Reproductive System (1st Edition)
• Reproductive System: Female (2nd and 3rd Editions) • Reproductive System: Male (2nd and 3rd Editions)
Dr. Katie M. Boes 6th edition • Bone Marrow, Blood Cells, and the Lymphoid/Lymphatic System
Dr. Erin M. Brannick 6th edition • Neoplasia and Tumor Biology
Dr. Melanie A. Breshears 6th edition • The Urinary System
Dr. Danielle L. Brown 5th and 6th editions • Hepatobiliary System and Exocrine Pancreas
Dr. Charles C. Capen 1st through 4th editions • Endocrine System
Dr. Cathy S. Carlson 5th and 6th editions • Bones, Joints, Tendons, and Ligaments
Dr. William W. Carlton 1st through 3rd editions
Eye and Ear (1st Edition)
Pathology of the Eye and Ear (2nd Edition) • The Eye and Ear (3rd Edition)
• Coeditor of the 2nd and 3rd Editions
Dr. Anthony W. Confer 1st through 6th editions • Urinary System (1st and 4th Editions) • The Urinary System (2nd, 3rd, and 6th Editions)
Dr. John M. Cullen 1st through 6th editions • Liver, Biliary System, and Exocrine Pancreas (1st through 4th Editions)
• Hepatobiliary System and Exocrine Pancreas (5th and 6th Editions)
Dr. Cecil E. Doige 1st through 3rd editions • Skeletal System (1st Edition)
• Diseases of Bone and Joints (2nd Edition)
• Bone and Joints (3rd Edition)
Dr. Richard R. Dubielzig 1st through 3rd editions • Dental Pathology
Dr. Amy C. Durham 6th edition
• Bone Marrow, Blood Cells, and the Lymphoid/Lymphatic System
Dr. Victor J. Ferrans 1st through 4th editions • Cardiovascular System (1st, 3rd, and 4th Editions)
Dr. Robert A. Foster 4th through 6th editions
Dr. Michael M. Fry 4th and 5th editions
• Pathology of the Cardiovascular System (2nd Edition)
•
•
Female Reproductive System (4th Edition)
Female Reproductive System and Mammary Gland (5th Edition)
• Female Reproductive System and Mammae (6th Edition)
• Male Reproductive System (4th through 6th Editions)
• Bone Marrow, Blood Cells, and Lymphatic System (4th Edition)
• Bone Marrow, Blood Cells, and the Lymphatic System (5th Edition)
Dr. Arnon Gal 5th and 6th editions • Cardiovascular System and Lymphatic Vessels
Dr. Howard B. Gelberg 3rd through 6th editions
Dr. Pamela Eve Ginn 3rd through 5th editions
• Alimentary System (3rd and 4th Editions)
• Alimentary System and the Peritoneum, Omentum, Mesentery, and Peritoneal Cavity (5th and 6th Editions)
• Integumentary System (3rd Edition)
• The Integument (4th and 5th Editions)
Dr. Ann M. Hargis 1st through 6th editions • Integumentary System (1st through 3rd Editions) • The Integument (4th through 6th Editions)
Dr. Donna F. Kusewitt 4th through 6th editions
Neoplasia and Tumor Biology
Dr. Philippe Labelle 6th edition • The Eye
Dr. Krista M.D. La Perle 4th and 5th editions • Endocrine System
Dr. Alfonso López 2nd through 6th editions
Respiratory System (2nd Edition)
Respiratory System, Thoracic Cavities, and Pleura (3rd Edition) • Respiratory System (4th Edition)
• Respiratory System, Mediastinum, and Pleurae (5th and 6th Editions)
Dr. N. James MacLachlan 1st through 3rd editions • Liver, Biliary System, and Exocrine Pancreas
Dr. Shannon A. Martinson 6th edition • Respiratory System, Mediastinum, and Pleurae
*1st edition as Special Veterinary Pathology, 2nd and 3rd editions as Thomson’s Special Veterinary Pathology, and the 4th through 6th editions as Pathologic Basis of Veterinary Disease
Authors Editions*
Dr. M. Donald McGavin 1st through 6th editions
Dr. Margaret A. Miller 6th edition
Chapter Title(s)
• Cellular and Tissue Responses to Injury (4th Edition)
• Cellular Adaptations, Injury, and Death: Morphologic, Biochemical, and Genetic Bases (5th Edition)
• Bone Marrow, Blood Cells, and Lymphatic System (4th Edition)
• Bone Marrow, Blood Cells, and the Lymphatic System (5th Edition)
• Muscular System (1st Edition)
• Muscle (2nd and 3rd Editions)
• Skeletal Muscle (4th and 5th Editions)
• Appendix: Photographic Techniques in Veterinary Pathology (5th and 6th Editions)
• Coeditor of the 2nd through 5th Editions
• Mechanisms and Morphology of Cellular Injury, Adaptation, and Death
• The Endocrine System
Dr. Andrew D. Miller 6th edition • Nervous System
Dr. Lisa M. Miller 5th and 6th editions • Cardiovascular System and Lymphatic Vessels
Dr. Donald L. Montgomery 3rd edition • The Nervous System
Dr. Derek A. Mosier 4th through 6th editions • Vascular Disorders and Thrombosis
Dr. Ronald K. Myers 4th and 5th editions • Cellular and Tissue Responses to Injury (4th Edition)
• Cellular Adaptations, Injury, and Death: Morphologic, Biochemical, and Genetic Bases (5th Edition)
Dr. Sherry Myers 6th edition • The Integument
Dr. Kimberly M. Newkirk 6th edition • Neoplasia and Tumor Biology
Dr. Shelley J. Newman 4th and 5th editions • Urinary System (4th Edition) • The Urinary System (5th Edition)
Dr. Bradley L. Njaa 5th and 6th editions • The Ear and Eye (5th Edition) • The Ear (6th Edition)
Dr. Erik J. Olson 6th edition • Bones, Joints, Tendons, and Ligaments
Dr. Roger J. Panciera 1st through 4th editions • Urinary System (1st and 4th Editions)
• The Urinary System (2nd and 3rd Editions)
Dr. James A. Render 1st through 3rd editions • Eye and Ear (1st Edition)
• Pathology of the Eye and Ear (2nd Edition)
• The Eye and Ear (3rd Edition)
Dr. Laura J. Rush 4th edition • Neoplasia and Tumor Biology
Dr. Gene P. Searcy 1st through 3rd editions • Hemopoietic System (1st and 2nd Editions)
• The Hemopoietic System (3rd Edition)
Dr. Paul W. Snyder 4th through 6th editions • Diseases of Immunity
Dr. Ralph W. Storts 1st through 3rd editions • Central Nervous System (1st and 2nd Editions)
Dr. Reginald G. Thomson 1st edition
Dr. Beth A. Valentine 3rd through 6th editions
• The Nervous System (3rd Edition)
• Editor
• Muscle (3rd Edition)
• Skeletal Muscle (4th through 6th Editions)
Dr. Hebert J. Van Kruiningen 1st and 2nd editions • Gastrointestinal System
Dr. John F. Van Vleet 1st through 5th editions • Cardiovascular System (1st, 3rd, and 4th Editions)
Dr. Arnaud J. Van Wettere 6th edition
Dr. Steven E. Weisbrode 2nd through 5th editions
Dr. Brian P. Wilcock 4th and 5th editions
• Pathology of the Cardiovascular System (2nd Edition)
• Cardiovascular System and Lymphatic Vessels (5th Edition)
• Hepatobiliary System and Exocrine Pancreas
• Diseases of Bone and Joints (2nd Edition)
• Bone and Joints (3rd and 4th Editions)
• Bones, Joints, Tendons, and Ligaments (5th Edition)
• Eye, Eyelids, Conjunctiva, and Orbit (4th Edition)
• The Ear and Eye (5th Edition)
Dr. William D.G. Yates 1st edition • Respiratory System
Dr. James F. Zachary 3rd through 6th editions • Cellular Adaptations, Injury, and Death: Morphologic, Biochemical, and Genetic Bases (5th Edition)
• Mechanisms and Morphology of Cellular Injury, Adaptation, and Death (6th Edition)
• Mechanisms of Microbial Infections (5th and 6th Editions)
*1st edition as Special Veterinary Pathology, 2nd and 3rd editions as Thomson’s Special Veterinary Pathology, and the 4th through 6th editions as Pathologic Basis of Veterinary Disease
• Nervous System (4th through 6th Editions)
• Coeditor of the 3rd through 5th Editions
• Editor of the 6th Edition
Acknowledgments for Illustrative Materials
We extend our deepest appreciation and thanks to colleagues throughout the world (truly an international effort), who have so generously provided their illustrative materials for use in the seventh edition. Although space limitations preclude listing them here, their names are credited in the figure legend for each illustration. Additionally, we extend our deepest appreciation to Drs. Barry G. Harmon, Elizabeth W. Howerth, and R. Keith Harris, who in their roles as Director of Noah’s Arkive, College of Veterinary Medicine, The University of Georgia have supported our efforts over the last two decades. We have attempted to credit each illustration to its original source; however, inadvertent errors will occur in assembling a textbook of this size. Please address concerns about credits to zacharyj@illinois.edu. We will make every effort to confirm the origin of the photograph and correct the credit before the book goes into a subsequent printing or edition.
Acknowledgment of Elsevier Staff and Associates
We thank the wide-ranging contributions of Elsevier staff: Jennifer Catando (Senior Content Strategist), Jennifer Wade (Senior Content Development Specialist), Maria Broeker (Senior Content Development Specialist), Rachel McMullen (Senior Production Manager), and Amy Buxton (Design Group). We would also like to thank Julie Mangoff, Project Manager, whose tireless effort and dedication brought this book to fruition. Their hard work, patience, and collaboration have made the revision process manageable and successful.
Digitally Enhanced Version
The digitally enhanced version of the seventh edition includes:
1. The entire printed content of the seventh edition in an easy to read and use format
2. The sections cited in the seventh edition that refer to online subject matter
3. The ten new appendices listed earlier in the section New to this Edition
4. Suggested readings for each chapter
5. Information of historical and clinical value for some disorders and disease mechanisms
6. Discussion of a general approach for performing an autopsy (see new Appendix C, Postmortem Examination [Autopsy] of Domestic Animal Species).
7. Discussion within each chapter of the postmortem procedures for examining tissues within each organ system
8. Discussions of tissue fixation, fixatives, specimen trimming, and artifacts in surgical biopsies (see new Appendix F, General Principles of Tissue Fixation and Processing through Appendix I, Surgical Biopsies—Procurement, Processing, and Sectioning Artifacts).
9. A glossary of abbreviations and terms used for each chapter
10. A listing of diseases with a real or suspected genetic basis for each organ system in Chapter 1, Mechanisms and Morphology of Cellular Injury, Adaptation, and Death (also see E-Table 1.2)
11. Discussion of the methods for gross specimen photography and photomicrography (Appendix B, Photographic Techniques in Veterinary Pathology)
Additionally, all of the selected readings available in the digitally enhanced version are linked to original abstracts in PubMed.
The inner front cover of the printed book includes information on accessing the digitally enhanced version.
Finally, it is our hope that materials provided in the digitally enhanced version can serve as the basis for course development for
instructors assigned the responsibility of teaching general, organ system, or diagnostic pathology in veterinary curricula and for instructors in related fields within university undergraduate and graduate curricula where the material is appropriate for course content.
The accompanying Evolve website includes an image collection with all images from the book for instructors to use.
Terminology Challenges
Much of the terminology used in veterinary pathology is common to that used in other veterinary courses and clinical medical fields. However, the precise meaning of a term depends on the context in which it is used, and in veterinary pathology the context is the response of cells, tissues, and organs to injury. In previous editions of this book, the name “dilated cardiomyopathy” has been used as a replacement for “dilatative cardiomyopathy” to identify this cardiovascular disorder. Dilated cardiomyopathy is also commonly used in other veterinary and human medical textbooks to name this disorder. However, in veterinary pathology, there is a valuable conceptual distinction between the terms “dilation” and “dilatation.” Dilation is an expansion of a lumen or orifice (e.g., sphincters, pupils, cervix, blood vessels). It occurs rapidly within physiologic limits established by the structure and function of the tissue or organ. Cardiac chambers dilate during diastole and contract during systole. Epinephrine will enhance cardiac dilation, but only within physiologic and structural limits. In contrast, dilatation is expansion of a lumen or orifice beyond its normal physiologic and structural limits. Dilatation is a pathologic condition (i.e., a response to injury), and it cannot occur rapidly. The term indicates that the organ has undergone remodeling as part of a chronic pathologic process in response to injury. A heart with dilatative cardiomyopathy has chambers that are far larger and misshapen in comparison to a dilated heart. On this basis, the term “dilatative cardiomyopathy” will be used in place of “dilated cardiomyopathy” in the seventh edition.
Veterinary Diagnostic Pathology
One of the goals of the seventh edition is to develop new appendices that can assist students in acquiring skill sets useful in antemortem or postmortem examinations in the practice of veterinary medicine. These appendices are listed in the section New to this Edition and focus on the processes involved in performing meaningful examinations that can result in a definitive diagnosis for the cause of the animal’s lesion(s) or death and to develop a final case report that will provide information of benefit to the owner/producer. There are many approaches to conducting such examinations, and they will vary among diagnostic units. However, they all have a common pattern of flow that is often modified as needed to best fit the resources and staff of a postmortem facility or an examination performed in a field/pasture or barn. These appendices, especially Appendix C, Postmortem Examination (Autopsy) of Domestic Animal Species and Appendix D, Recognition and Interpretation of Macroscopic (Gross) Lesions, illustrate and discuss processes that have been used and frequently updated in academic diagnostic laboratories for over four decades. They are “works in progress” and will need to be updated in subsequent editions. However, because these appendices are online, they can also be updated within the lifespan of this edition. Please contact the editor zacharyj@illinois.edu if you have corrections, ideas for improvements, and/or could serve as a resource for better images.
About the Covera
Feline infectious peritonitis (FIP) is a severe, usually fatal, viral disease of cats caused by a mutated strain of feline enteric coronavirus called FIP virus. FIP virus initiates a cascade of events that result in immune complex vasculitis (i.e., phlebitis) affecting all organ systems, most notably the kidney. The intensity of the cat’s cell-mediated immune response to the virus appears to determine the outcome of the infection. Cats with a strong cell-mediated response do not develop FIP. Cats with a weak cell-mediated response have the dry (noneffusive) form; cats with no cell-mediated response have the wet form (effusive). An effective humoral response appears to increase the severity of disease. The mechanism of injury is chronic-active pyogranulomatous inflammation (i.e., vasculitis and perivasculitis) and its mediators and degradative enzymes. Gross lesions include gray-white nodules of varied sizes that have a perivascular pattern of distribution and in some cases a linear pattern following blood vessels in serosa and mesenteries (dry form). Body cavities may contain a thick yellow-white exudate containing fibrin and pyogranulomatous inflammatory cells (wet form).
Cats encounter feline enteric coronavirus by ingestion. The virus replicates primarily in mature enterocytes of the small intestine, spreads into the lamina propria, and then into macrophages within Peyer’s patches. It is within these macrophages that feline enteric coronavirus mutates into FIP virus. Through mutation, it acquires virulence factors that allow it to infect and replicate in cells of the monocyte-macrophage system, resulting in rapid dissemination of the virus throughout the body via leukocyte trafficking to infect additional macrophages. Virus-infected macrophages appear to target small and medium-sized veins of serosal membranes and tissues, cause damage to endothelial cells, and are recognized as foreign by the cat’s innate (inflammation) and adaptive (cell-mediated and humoral) defense mechanisms. This process likely involves activation of the leukocyte adhesion cascade and binding of macrophages and monocytes to endothelial cells facilitated by ligand-receptor
aCover artwork is not drawn to scale; colors employed are used, in part, to emulate hematoxylin and eosin (H&E) staining of cells.
interactions and the activation of acute inflammation via proinflammatory cytokines released from activated macrophages and monocytes. All of these processes result in injury of vascular and perivascular tissues (i.e., vasculitis and perivasculitis).
Tissue macrophages/monocytes provide a source of viral antigens in and around venules, and if adequate antibody is present, antigenantibody complexes form, and a type III hypersensitivity response ensues. These complexes activate complement, resulting in chemotaxis and accumulation of neutrophils via the leukocyte adhesion cascade. Additionally, they also activate tissue macrophages, leading to the secretion of a variety of proinflammatory cytokines that act on endothelial cells to increase neutrophil and mononuclear cell chemotaxis into the area and open tight junctions of endothelial cells (increased permeability), thereby allowing leakage of plasma and fibrin into body cavities. These mechanisms result in the vasocentric pyogranulomas and pyogranulomatous inflammation, fibrinous effusions, and fibrinous polyserositis, so characteristic of FIP. A type IV hypersensitivity reaction may also be involved in the pathogenesis of some pyogranulomas. It appears that the commonly used categories of wet and dry forms and type III and type IV hypersensitivities are based more on clinical characteristics and immunologic tests, respectively, than on any morphologic criteria. Experimental studies have shown that there are no distinct histopathologic lesions that distinguish wet from dry cases, type III from type IV hypersensitivities, or acute/subacute cases from chronic cases.
In Conclusion
No greater impact can be made on students in their veterinary education than by teachers who are willing to share their expertise, knowledge, and practice experiences with them. We hope the seventh edition of Pathologic Basis of Veterinary Disease and its mechanistic approach to disease will assist in this process, cultivate student interest in and understanding of the pathogeneses of diseases, and perhaps transform the way pathology is taught in veterinary curricula.
JAMES F. ZACHARY
Introduction: Fundamentals for Understanding Veterinary Pathology, 1
Margaret A. Miller and James F. Zachary
SECTION I Cellular and Molecular Mechanisms of Disease (General Pathology)
1 Mechanisms and Morphology of Cellular Injury, Adaptation, and Death, 16
Margaret A. Miller, L. Tiffany Lyle, and James F. Zachary
2 Vascular Disorders and Thrombosis, 74
Derek A. Mosier
3 Inflammation and Healing, 104
Mark R. Ackermann
4 Mechanisms of Microbial Infections, 171
James B. Stanton and James F. Zachary
5 Diseases of Immunity, 295
Paul W. Snyder
6 Neoplasia and Tumor Biology, 341
Erin M. Brannick, Kimberly M. Newkirk, and Deanna M.W. Schaefer
SECTION II Pathology of Organ Systems
7 Alimentary System and the Peritoneum, Omentum, Mesentery, and Peritoneal Cavity, 396
Sean T. Spagnoli and Howard B. Gelberg
8 Hepatobiliary System and Exocrine Pancreas, 486
Arnaud J. Van Wettere and Danielle L. Brown
9 Respiratory System, Thoracic Cavities, Mediastinum, and Pleurae, 547
Alfonso Lόpez and Shannon A. Martinson
10 Cardiovascular System, Pericardial Cavity, and Lymphatic Vessels, 643
Arnon Gal and Fernanda Castillo-Alcala
11 The Urinary System, 699
Mee-Ja M. Sula and Laura V. Lane
12 Endocrine System, 767
Margaret A. Miller
13 Bone Marrow, Blood Cells, and the Lymphoid/Lymphatic System, 809
Amy C. Durham and Katie M. Boes
14 Nervous System, 892
Andrew D. Miller and Brian F. Porter
15 Skeletal Muscle, 992
Beth A. Valentine
16 Bones, Joints, Tendons, and Ligaments, 1037
Erik J. Olson, Jaclyn A. Dykstra, Alexandra R. Armstrong, and Cathy S. Carlson
17 The Integument, 1095
Monika M. Welle and Keith E. Linder
18 Female Reproductive System and Mammae, 1263
Robert A. Foster and Christopher Premanandan
19 Male Reproductive System, 1308
Robert A. Foster and Christopher Premanandan
20 The Ear, 1336
Bradley L. Njaa
21 The Eye, 1379
Philippe Labelle
SECTION III Appendices, Veterinary Diagnostic Pathologyb
Appendix A: Communication, Collaboration, and Consultation in Veterinary Pathology
Erin M. Brannick
Appendix B: Photographic Techniques in Veterinary Pathology
M. Donald McGavin
Appendix C: Postmortem Examination (Autopsy) of Domestic Animal Species
Patrick J. Roady and James F. Zachary
Appendix D: Recognition and Interpretation of Macroscopic (Gross) Lesions
James F. Zachary and Patrick J. Roady
Appendix E: Diagnoses in Veterinary Pathology
Margaret A. Miller and James F. Zachary
Appendix F: General Principles of Tissue Fixation and Processing
James F. Zachary and M. Donald McGavin
Appendix G: Fixatives and Fixation
M. Donald McGavin, Margaret A. Miller, and James F. Zachary
Appendix H: Fixation and Trimming of the Brain, Spinal Cord, and Nerves
M. Donald McGavin, Shelley J. Newman, and James F. Zachary
Appendix I: Surgical Biopsies—Procurement, Processing, and Sectioning Artifacts
M. Donald McGavin and James F. Zachary
Appendix J: Gross Examination and Infusion Fixation of the Lung
M. Donald McGavin and James F. Zachary
Appendix K: Necropsy Techniques by Organ System Contributors of Pathology of Organ System Chapters
INTRODUCTION
Fundamentals for Understanding Veterinary Pathology
Margaret A. Miller and James F. Zachary
Key Readings Index
Information Fundamental for Effective
Use of this Book, 1
Diagnoses in Veterinary Pathology, 2
Language of Veterinary Pathology, 3
Recognition and Interpretation of Lesions, 4
Pattern Recognition in Gross (Macroscopic) Examinations, 4
Specular Highlights, 4
Colors of Normal Tissues and Organs, 7
Evaluation of Lesions Affecting Tissues and Organs, 9
Key Element 1: Distribution of Lesions, 9
Key Element 2: Quantity of Lesions, 9
Key Element 3: Colors of Lesions, 9
Key Element 4: Shapes of Lesions, 11
Veterinary pathology is a medical specialty that studies the lesions and mechanisms of diseases affecting animal species. Veterinary pathologists in North America, after receiving their degree in veterinary medicine (DVM, VMD), train in the specialty for an additional 3 to 5 years and are certified by examination as (1) anatomic pathologists, who investigate lesions observed on the postmortem floor and with a microscope, or as (2) clinical pathologists, who study the cytologic, microscopic, and biochemical alterations of blood, bone marrow, urine, and other body fluids and/or aspirates. Similar certification programs also exist in Europe and Japan. Although there is some overlap in subject matter between anatomic and clinical pathology, the focus of this book is on anatomic pathology. Clinical pathology is taught separately in most veterinary curricula, and there are excellent books covering this subject matter.
In the practice of veterinary pathology, the goal is to answer a question or solve a problem. The question depends on the nature of the investigation. In diagnostic pathology, an autopsy (syn: necropsy/ postmortem examination) may be performed to (1) determine the cause of death of an individual animal or multiple animals in a herd, flock, kennel, or cattery or (2) explain decreased production within these groups. Surgical pathology involves sampling a tissue by biopsy or fine needle aspirate (i.e., cytology) and using the information acquired from evaluating the specimen to establish a diagnosis, prognosis, and therapy for the living animal. In forensic pathology, the purpose of an autopsy is to determine the cause of death from a legal perspective. Lastly, experimental pathology occurs in research settings where the pathologist designs laboratory studies with the goal of correlating morphologic lesions with clinical, functional, genetic, immunologic, and/ or biochemical information to elucidate the pathogeneses of diseases.
Although veterinary pathologists may have differing practice specializations, they have a common goal of sharing their expertise with veterinary students through classroom and laboratory teaching, conducting pathology rounds and seminars, and writing chapters in textbooks as examples. Most veterinary school graduates will practice internal medicine or surgery rather than pathology;
Key Element 5: Sizes of Lesions, 11
Key Element 6: Firmness (Density) of Lesions, 12
Key Element 7: Surface Texture of Lesions, 12
Diagnostic Pathology, 12
Macroscopic (Gross) Reports, 12
Microscopic Reports, 12
nevertheless, pathology is an integral part of veterinary education and practice. Pathology is the link between basic sciences, such as anatomy and physiology, and the clinical sciences and is the foundation for a lifetime of learning, diagnosing, and understanding disease in living and dead animals. The practicing veterinarian and the veterinary pathologist also form a team at the forefront of animal and public health.
Information Fundamental for Effective Use of this Book
Pathology is the investigation of disease. It encompasses the recognition and interpretation of structural and functional alterations (i.e., lesions) of cells, tissues, and organs, as well as the microbial, parasitic, biochemical, genetic, and molecular mechanisms that cause disease. As an effort to make understanding this information straightforward, this book has been divided into two sections. The first section contains 6 chapters covering general pathology (Cellular and Molecular Mechanisms of Disease); the second section contains 15 chapters covering systemic pathology (Pathology of Organ Systems). Lastly, there is an extensive online E-section that contains 11 appendices that discuss and illustrate the fundamentals of veterinary diagnostic pathology, such as Appendix C, Postmortem Examination (Autopsy) of Domestic Animal Species and Appendix D, Recognition and Interpretation of Macroscopic (Gross) Lesions. The section on general pathology is an examination of the responses of cells and tissues to injury with a focus on the causes of and processes involved in these responses. Chapters in this section cover cellular adaptations (degenerative, regenerative, or restorative), vascular disorders, inflammation, and neoplasia as well as mechanisms of infectious diseases and disorders of immunity. These categorizations simplify the teaching and learning of general pathology. In the living body, however, cell injury provokes a variety of vascular, inflammatory, and immune-mediated responses in addition to disturbances of growth that occur concurrently or in rapid succession over time.
Types of Diagnoses*
Type of Diagnosis
Clinical diagnosis
Gross (macroscopic) diagnosis
Morphologic diagnosis
Differential diagnosis
Definitive diagnosis
Etiologic diagnosis
Information Used to Make the Diagnosis
Signalment, history, and physical examination
Physical examination, endoscopic examination, exploratory surgery, or autopsy findings
Autopsy findings (macroscopic and microscopic lesions)
Autopsy findings, signalment, and history
Autopsy findings, plus the results of ancillary tests
Microbiology test results, plus information from autopsy findings
*Tyzzer’s disease (Clostridium piliforme) used as an example.
Systemic pathology is the study of disorders that affect a “system,” meaning one or more organs of the body of the entire animal. It is not a separate discipline from general pathology but a different approach to studying disease, in which the principles of general pathology are applied at the level of a tissue, organ, or the entire body. The section on systemic pathology is organized for teaching purposes by grouping materials into chapters based on traditionally defined “organ systems.” Nevertheless, students must remember that disease seldom, if ever, affects only one tissue or organ. It also helps to remember that most tissues and organs respond in similar ways to a particular type of injury. As a result, there is value in mastering the concepts of general pathology before studying systemic pathology. There is no optimal order in which to teach individual organ system chapters in systemic pathology, so this subject matter may be taught in different sequences in veterinary curricula.
The goal of understanding and learning information discussed and illustrated throughout this book is based on the assumption that students have acquired and retained information in other courses that will contribute to making this aim successful. However, to ensure this outcome, such prerequisite materials are summarized in the sections that follow.
Diagnoses in Veterinary Pathology
Diagnosis is a common and important goal in veterinary practice and in veterinary pathology (Table I.1).
• Clinical Diagnosis: A clinical diagnosis is based mainly on the signalment (e.g., age, sex, breed), history, and findings of the physical examination. Even with data from clinical pathologic analyses or diagnostic imaging, the clinical diagnosis may only be tentative or presumptive.
• Gross (Macroscopic) Diagnosis: The establishment of a grossa (i.e., macroscopic) diagnosis results from information obtained from a physical examination, endoscopic examination, exploratory surgery, or autopsy and is based on the ability of the clinician or prosectorb to recognize and interpret macroscopic lesions in tissues and organs. In some cases, the gross diagnosis is a definitive diagnosis (e.g., bone fractures and other traumatic injuries). An experienced pathologist can diagnose certain infectious, nutritional, or neoplastic diseases with accuracy at the macroscopic level; however, most
aThe word “gross” as applied herein is an adjective that means “visible to the naked or unaided eye” and is used in pathology in medical terms such as gross lesions, gross findings, or gross examination, as examples. The term “macroscopic” is synonymous with the term “gross.”
bThe individual who conducts the dissection, examination, and evaluation of the animal during an autopsy.
Actual Diagnosis
Anterior abdominal pain
Mild icterus
Liver disease
Multifocal necrotizing hepatitis
Acute multifocal necrotizing hepatitis
Tyzzer’s disease
Hepatic salmonellosis
Viral hepatitis
Tyzzer’s disease
Clostridial hepatitis or Clostridium piliforme hepatitis
DDDEMT: Examples of the Nomenclature Used to Construct a Morphologic Diagnosis*
*This table provides examples of how nomenclature can be used to construct a morphologic diagnosis. It is not intended to be all inclusive and may vary from patterns used in other veterinary colleges or schools.
†Used only for diseases of the lungs.
‡The terms listed in the row to the right of this word are provided as examples. There are many additional terms that are explained and used throughout this book. §Pneumonia is recognized as the term to characterize inflammation of the lung.
gross examinations are followed by microscopic (i.e., histologic) examinationsc to establish morphologic diagnoses.
• Morphologic Diagnosis: A morphologic diagnosis is a clear and concise naming of a pattern of structural changes observed in a gross or microscopic lesion. Pathologists develop morphologic diagnoses by recognizing and interpreting gross lesions observed at autopsy or in biopsy specimens and microscopic lesions in histologic sections or cytologic preparations. A morphologic diagnosis names and categorizes lesions based on the following observations of the injury: degree, duration, distribution, exudate, modifiers, and tissue (DDDEMT). The nomenclature of each of these DDDEMT injury observations is listed in Table I.2.
A morphologic diagnosis can be based on gross or histologic lesions. It should categorize the lesion—as degeneration or necrosis, a vascular disturbance, inflammation, or as a disturbance of growth—and indicate the affected tissue(s) and/or organ(s). As an example, the word necrosis is often a part of a morphologic diagnosis that categorizes a lesion; however, it needs one more word (e.g., hepatic) to identify the affected tissue. Thus, hepatic necrosis is a complete morphologic diagnosis, although it may need a modifier or two for explanatory purposes (see Table I.2). For example, multifocal (randomly distributed) hepatic necrosis (i.e., multifocal hepatic necrosis) implicates an infection, whereas lobular hepatic
cExamination of tissues or organs using a microscope, most commonly a light microscope.
Table I.1
Table I.2
necrosis (e.g., centrilobular hepatic necrosis) is usually the result of ischemic, metabolic, or toxic injury. Additional modifiers for descriptive purposes could include, for example, the degree of severity and the duration of injury. In some settings, the morphologic diagnosis is the end point (i.e., definitive diagnosis). More often, it is the basis for the formulation of a differential diagnosis.
• Differential Diagnosis: A differential diagnosis is a list of diseases or conditions and their morphologic diagnoses that could cause the clinical findings or observed lesions. The list (descending rank order [most likely → least likely]) should not be exhaustive, but rather should contain those diseases (usually three to five disease entities) that are most likely to have caused the lesions in an animal with the recorded signalment and history. Generally, the list is initially developed from the clinical findings and then focused as more diagnostic information becomes available based on the results of a postmortem examination or surgical biopsy and the results of other supporting laboratory tests.
• Definitive Diagnosis: The ultimate goal in the examination of a specimen is establishing a definitive diagnosis. The definitive diagnosis identifies the specific disease or condition causing the lesions. In some situations, a morphologic diagnosis is a definitive diagnosis (e.g., naming of a neoplasm). More often, especially in infectious diseases, the morphologic diagnosis is the starting point. For example, if a morphologic diagnosis of multifocal hepatic necrosis or multifocal necrotizing hepatitis suggests an infectious disease, then the identification of the microbial agent that causes the disease will serve to establish the definitive diagnosis. Ancillary tests, such as microbiology, parasitology, chemical analyses, and immunohistochemistry can be essential in refining a differential diagnosis to reach the definitive diagnosis. Ancillary tests are selected based on the nature of the disease. For example, a poorly differentiated mast cell tumor might necessitate obtaining more information from histochemistry, immunohistochemistry, or perhaps even molecular diagnostics, such as polymerase chain reaction (PCR) amplification of nucleic acids, whereas evaluation of a hematoxylin and eosin (H&E)-stained histologic section may suffice for a well-differentiated mast cell tumor.
Neoplastic diseases are one of a few situations in which a morphologic diagnosis (i.e., the name of the tumor) is also the definitive diagnosis. Lesions caused by trauma (e.g., fractures, hemorrhages) are additional examples in which morphologic diagnoses are also definitive diagnoses. Lesions of nutritional deficiencies or toxic diseases are seldom so specific and generally implicate chemical injury without incriminating a particular substance; thus, a definitive diagnosis is unlikely, and a differential diagnosis is more likely. Infectious diseases, unless the lesions are highly specific, also result in a list of potential bacteriologic, mycologic, virologic, or parasitologic causes (i.e., differential diagnosis). Microbiologic analyses are then required for identification of a particular cause (e.g., genus and species of the etiologic agent) to establish a definitive diagnosis.
• Etiologic Diagnosis: An etiologic diagnosis emphasizes the cause, rather than the morphologic features, of a disease. For example, in a foal with Tyzzer’s disease, the morphologic diagnosis of acute multifocal necrotizing hepatitis could be replaced or supplemented with an etiologic diagnosis of clostridial hepatitis once the cause (Clostridium piliforme) is identified. Importantly, an etiologic diagnosis of clostridial hepatitis does not implicate a particular species of Clostridium, and so it is less useful than the definitive diagnosis of Tyzzer’s disease (C. piliforme infection).
Language of Veterinary Pathology
Throughout this book, students will use terminology in common with the vocabulary used in other veterinary courses; however, they
will also encounter new terminology that is essential to understanding veterinary pathology. The acquisition and use of this new terminology are based on having a clear understanding of the meaning of five essential terms:
• Cell: The smallest component of an animal’s structure that is capable of independent survival and function.
• Tissue: A term used to identify structural groupings of cells within an animal’s body. There are four main types of tissue: connective, muscle, nervous, and epithelial. Epithelial tissue contains the largest number of specific cell types within this classification system and includes, as examples, cells of the skin (e.g., keratinocytes), intestinal villi (e.g., enterocytes), and liver (e.g., hepatocytes).
• Organs/organ systems: The end-product of embryologic development is the arrangement of cells and tissues into functional units (i.e., organs/organ systems) that serve a need within an animal’s body.
• Structure: The configuration, organization, and physical (or physiologic) roles of cells, tissues, and organs/organ systems in homeostasisd and in response to injury and disease.
• Function: The metabolic, biochemical, and genomic/molecular processes of cells, tissues, and organs/organ systems in homeostasis and in response to injury and disease.
Students should also remember that pathology is the study of disease and that the word pathology is not equivalent to the word lesion. A lesion is a structural abnormality in a tissue or organ. All too often, the phrase “no pathology is observed” is heard in a lecture, seminar, or medical rounds or is read in a journal article or clinical report. This phrase would be more correctly expressed or written as “no lesion is observed.” Likewise, all lesions by definition are pathologic, so it is a mistake or redundant at best to refer to pathologic lesions. Additionally, although the vocabulary of pathology is common to that used in other veterinary courses, certain words mean one thing in one course or subject area, such as a tissue, and something quite different when used in another course or in describing a different tissue. Indeed, the precise meaning—and precision is the object in writing or speaking about pathology—of a word depends very much on the context. For example, the word malacia, which literally means softening, implies a lack of mineralization when applied to bones, but when applied to the brain, it means liquefactive necrosis. Finally, the term necrosis is a particularly important word used in this book, and it is discussed and illustrated extensively in Chapter 1, Mechanisms and Morphology of Cellular Injury, Adaptation, and Death. It means death or, more precisely, the structural changes that follow death, not of the animal, but of cells within tissues and organs in the animal. The basis for recognizing and interpreting many of the lesions discussed and illustrated in this book is the result of necrosis of cells in tissues and organs.
Throughout this book, students will also study many disorders involving inflammatory, noninflammatory, degenerative, and proliferative processes, as well as many other types of responses to injury. The grammatic structure used to identify and link these processes to specific types of injury are rooted historically in Greek terminology employing noun-combining forms. The most common noun-combining forms used in this book are:
• -itis: inflammatory diseases or disorders in tissues or organs (e.g., steatitis, bronchitis, or hepatitis).
• -opathy: noninflammatory diseases or disorders in tissues or organs (e.g., neuropathy, hepatopathy, lymphadenopathy).
dThe existence of cells, tissues, and organs/organ systems in a physiologic condition that is considered normal for each type of cell, tissue, and organ/ organ system.
• -osis: noninflammatory conditions (e.g., hepatosis), degenerative conditions (e.g., steatosis), ongoing processes (e.g., cirrhosis), or existing states (e.g., calcinosis) in tissues or organs.
• -omegaly: enlargement of tissues or organs (e.g., splenomegaly, hepatomegaly).
• -ectasis: dilation or distention of tubular structures (e.g., bronchiectasis, lymphangiectasis).
• -penia: a deficiency (e.g., osteopenia, cytopenia).
• -trophy: nourishment, development (e.g., atrophy, hypertrophy).
• -genesis: beginning, development, or production of something (e.g., agenesis, osteogenesis, carcinogenesis, pathogenesis).
• -cele: a distended space or sac within a tissue or organ (e.g., meningocele, hematocele).
• -oma: a mass or tumor, such as a granuloma or fibroma/fibrosarcoma, respectively.
Recognition and Interpretation of Lesions
Veterinarians who enter the field of anatomic pathology often do so because they enjoy the challenge of solving a problem (a mystery), much like detectives or investigators. The pathologist obtains a history, develops a diagnostic strategy, and evaluates a surgical biopsy specimen or performs a postmortem examination. Recognition and interpretation of lesions and the results of other nonmorphologic laboratory tests are part of the evidence that the pathologist collects to evaluate and solve the case. Such nonmorphologic techniques include, as examples, the isolation and identification of infectious agents or toxicants, quantification of chemical deficiencies or excesses, and the detection of genetic abnormalities. In most cases, the evidence fits into a pattern that establishes a definitive diagnosis and thus contributes to providing an answer and/or closure for livestock and pet owners. In some cases, however, a definitive diagnosis eludes pathologists and their collaborators.
Information acquired from a postmortem examination is based, in part, on the recognition and interpretation of morphologic changes, specifically of the macroscopic and microscopic lesions that develop in injured cells, tissues, organs, and organ systems. There are many causes of cellular dysfunction and injury, and they are discussed in detail in Chapter 1, Mechanisms and Morphology of Cellular Injury, Adaptation, and Death and in all the chapters of this book.
In veterinary school, students will learn to recognize, evaluate, and interpret lesions at the macroscopic level because as practicing veterinarians they will observe tissues and organs through physical, endoscopic, otoscopic, and ophthalmoscopic examinations as well as through exploratory surgery and postmortem examinations. Achieving these goals is dependent on acquiring a knowledge base from courses in anatomy and pathology during the veterinary curriculum and concurrently learning how to express this information verbally and in writing to colleagues in practice settings during clinical rotations and to clients in clinical practice.
Lesions are changes in the normal morphologic characteristics of cells in a tissue, organ, or organ system. They most commonly arise from cellular dysfunction or injury that alters cellular homeostasis. There are approximately 220 types of somatic cells in an animal’s body. Each of these cell types has an established “normal” morphology for the individual cell and for how these cells are arranged into groups that form the structure of tissues, organs, or organ systems. Additionally, each tissue type has a unique microcirculation (i.e., microvasculaturee) and
eThe portion of the vascular system responsible for exchange of nutrients and waste products between blood and extravascular tissue (for more detail see Chapter 2, Vascular Disorders and Thrombosis).
vascular/lymphatic drainage pattern that also contribute to their color. Therefore, every tissue, organ, or organ system has an established morphologic pattern that is considered normal for macroscopic and microscopic observations. During macroscopic (gross) evaluations, a clinician or pathologist/prosector must (1) recognize the structure and appearance (i.e., gross morphology) of normal tissues and organs and, most importantly, (2) recognize morphologic changes (i.e., patterns) in these tissues and organs that would be interpreted as lesions.
Pattern Recognition in Gross (Macroscopic) Examinations
During a postmortem examination, veterinary pathologists methodically examine all the tissues, organs, and organ systems of the animal and identify and characterize the gross (macroscopic) lesions. They recognize that specific diseases or disease processes (mechanisms) have lesions that occur consistently with a particular disease or disease process and thus the lesions are pathognomonic (i.e., distinctively characteristic of a particular disease) for a specific disease or disease process. This recognition-interpretation-correlation process is termed pattern recognition. Veterinary pathologists over the last century have documented patterns of lesions that are consistent with and diagnostic of a wide array of diseases and mechanisms of disease occurring in animals. These patterns, in part, serve as the basis for materials that are discussed and illustrated in the pathology of organ systems courses in veterinary school curricula. Pattern recognition is an analytic process used to develop morphologic diagnoses and/or determine the mechanism of injury (pathogenesis), and is based on the morphologic characteristics of the gross lesions observed during the postmortem examination. These characteristics include distribution, quantity, color, shape, size, firmness (density), and surface texture. In addition, the signalment (e.g., species, age, sex, breed) of the affected animal is also valuable information in recognizing a potential pattern. Specific lesion patterns have been documented for specific diseases such as, for example, (1) feline infectious peritonitis, (2) Johne’s disease (paratuberculosis), (3) end-stage liver (cirrhosis), (4) porcine pleuropneumonia, and (5) congestive and hypertrophic cardiomyopathies. Patterns have also been documented for specific mechanisms of injury, such as (1) chronic pulmonary congestion and edema, (2) chronic passive hepatic congestion (nutmeg liver), (3) hydrothorax, (4) hydronephrosis, and (5) herniation of the parahippocampal gyri. The thought processes of pattern recognition are summarized and illustrated in Table I.3. Additionally, lesion patterns can occur in a single tissue or organ, suggesting a targeted disease, or be more extensive and involve a collection of tissues or organs, suggesting a systemic disease.
For students, the ability to recognize and interpret patterns of lesions will be acquired in veterinary school and refined during their careers. There are numerous diagnostically useful patterns that will be reinforced throughout the Pathology of Organ Systems chapters of this book. Recognition of patterns exhibiting acute versus chronic changes, focal or multifocal versus diffuse changes, and active/primary versus passive/secondary processes, as examples, will also be very useful. Pattern recognition is covered in greater detail in Appendix D, Recognition and Interpretation of Macroscopic (Gross) Lesions. The colors of tissues and organs and the key characteristics of lesions that serve as the basis to recognize and interpret patterns in veterinary practice are discussed in the sections that follow; however, students must first recognize the appearance of specular highlights in gross photographs.
Specular Highlights
Specular highlights are bright white areas of varied sizes and shapes that occur on the surfaces of tissues and organs in photographs. This
Pattern
Recognition in Postmortem Examinations
STEP 1: ASSESS THE SIGNALMENT (E.G., SPECIES, AGE, SEX, BREED) AND HISTORY (E.G., DIET, HOUSING/ENVIRONMENT, CLINICAL SIGNS).
Example 1
Information Growing female pig
Example 1†
Postmortem findings
Example 2
Example 3
Young adult male cat Older adult female dog
STEP 2: IDENTIFY AND DESCRIBE THE GROSS (MACROSCOPIC) LESIONS.*
Example 2‡
• Cranioventral lung consolidated and firm (n, normal parenchyma)
• Cranioventral hyperemic (dark red to purple) areas from acute lobular inflammation (arrows)
• Cranioventral areas of chronic inflammation (dark pink to gray-tan areas, arrowheads)
• Peritoneal and pleural cavities filled by amber-colored fluid (asterisks)
• Gray-white nodules and plaques (arrows) involving serosal surfaces and vasculature of the intestine, peritoneum, kidney, and liver
• Strands of gray-white fibrin span peritoneal and pleural surfaces (arrowheads)
Example 3§
• Contracted kidney with pitted and nodular (white arrowheads) cortical surface
• Thickened and opaque (fibrosis) capsule (asterisks) adhered to cortex
• Gray-white fibrosing (chronic) inflammation at cortical surface (arrows) and in renal interstitium (black arrowheads)
Dorsal surface Dorsal section
Key
Elements
Pattern Recognition in Postmortem Examinations—cont’d
STEP 3: CHARACTERIZE THE PATTERN(S) OF THE LESIONS BASED ON THE KEY ELEMENTS OBSERVED IN STEP 2.
Example 1
Distribution Locally extensive cranioventral (cranioventral lung lobes)
Quantity
Two-thirds of cranioventral lung lobes affected; approximately half of total lung volume affected
Color Red to dark-red to gray-tan
Shape Lobular pattern matches the shape of lung lobules
Size Area of the cranioventral lung lobes
Firmness (density)
Firmer than normal pulmonary parenchyma
Surface texture Mostly smooth with patchy roughening because of fibrinous exudate
Example 2
Perivascular pattern with linear streaks following blood vessels in serosa, peritoneum, and pleura (see arrows in previous figure)
Numerous nodules and plaques; abundant fibrinous exudate (see figure)
Gray-white to yellow (see arrows in figure)
Nodules, plaques, and linear streaks (see distribution and arrows in figure)
Varied sizes, nodules (mm in diameter) (see arrows in figure)
Firm nodules; soft plaques and strands of fibrin
Shaggy (abundant fibrin) and nodular (granulomas)
Example 3
Capsule and cortical interstitium (fibrosis)
Entire capsule and >75% cortical interstitium affected
Gray-white bands (fibrous tissue) Gray-white nodules and poorly demarcated areas of fibrosis and inflammation
Nodular to conical or irregularly shaped patches and bands
Varied sizes, nodules (mm in diameter)
Fibrous bands and areas of fibrosing inflammation are firmer than normal renal parenchyma
Smooth (mature fibrous tissue in capsule), but nodular because of fibrous contraction of cortical parenchyma
STEP 4: BASED ON OBSERVATIONS IN STEPS 2 AND 3, INTERPRET THE LESIONS AND DEVELOP MORPHOLOGIC DIAGNOSES AND DIAGNOSTIC REPORTS.
Example 1
Morphologic diagnosis
Common name for the disease
Suppurative and lobular bronchopneumonia
Porcine enzootic pneumonia
Causative agent Mycoplasma hyopneumoniae
Mechanism (pathogenesis pathway)
Inhalation of bacteria → bronchial and bronchiolar mucosa → lysis of ciliated epithelial cells → loss of function (mucociliary apparatus) → dependent (cranioventral) settling → terminal bronchioles and alveoli → bronchointerstitial pneumonia → acute and chronic inflammation with hyperplasia of bronchus-associated lymphoid tissue → suppurative bronchopneumonia
Example 2
Fibrinous and granulomatous peritonitis, pleuritis, and vasculitis
Ingestion of virus → infection of small intestinal villous epithelial cells → viral mutation → infection of and replication in macrophages → regional and systemic trafficking → macrophage activation and targeting to veins → immune recognition of virus-infected macrophages → pyogranulomatous phlebitis → pyogranulomatous vasculitis and polyserositis
Example 3
Chronic tubulointerstitial nephritis
Chronic interstitial nephritis
Bacterial or viral septicemias
Toxins
Immune complexes
Septicemia/viremia/toxemia/immune complexes → injury of interstitial endothelial cells → cell death → inflammation and fibrosis → injury of proximal tubular epithelial cells → cell death → inflammation and fibrosis → interstitial fibrosis → chronic tubulointerstitial nephritis
*Gross lesions (also known as: macroscopic lesions) are the morphologic changes observed visually (by sight using unaided eyes) in tissues and organs during a postmortem examination.
† Image courtesy Dr. A. López, Atlantic Veterinary College.
‡Image courtesy Dr. H. Gelberg, College of Veterinary Medicine, Oregon State University.
§Image courtesy Dr. M.D. McGavin, College of Veterinary Medicine, University of Tennessee
book uses over 1000 photographs to describe and illustrate the processes involved in the recognition, interpretation, and diagnosis of gross (macroscopic) lesions, and specular highlights will frequently be observed in many of these images. In postmortem environments, photography of gross lesions, in part, involves using a light source such as the sun, room lights, studio lights, and/or camera flash units to fully and properly illuminate the colors of the gross specimen and to create shadows on its surface to reveal its modeling and texture (for more information on lighting and specimen photography, see Appendix B, Photographic Techniques in Veterinary Pathology). As a result of this lighting, many of these photographs will have specular highlights on the surfaces of the tissues and organs. They will occur on tissues and organs whose surfaces are normal and on surfaces with lesions. Students must be able to (1) recognize specular highlights in gross photographs and (2) differentiate them from gross lesions.
Because specular highlights are white spots (or areas) of varied shapes and sizes, they must be differentiated from whitish-gray to light yellow lesions, such as those caused by fibrin, fibrosis, acute or chronic inflammatory exudates, or surface mineralization. Specular highlights are “bright” (always the same color) white (i.e., RGB 255,255,255) and assume a wide array of sizes (millimeters to centimeters) and shapes (pinpoint to circular to elliptical) based on the morphology of the surface of the affected specimen ( Fig. I.1 ). Surfaces that are smooth (flat) and “shiny,” such as those covered by serosae (e.g., pleurae [lung] and peritonea [intestine]), can have large specular highlights (centimeters at the widest point; see Fig. I.1 , A–C ). In addition, highlights can be more prominent when the surfaces are wet (water or other bodily fluids) or have a convex shape. Surfaces that are roughened and/or granular can have pinpoint to small highlights (millimeters at the widest point; see Fig. I.1 , D–F ). Roughened surfaces of tissues and organs usually result from a variety of types of specific cell injury (see Chapter 1 , Mechanisms and Morphology of Cellular Injury, Adaptation, and Death) and from inflammatory responses, such as active hyperemia, fibrinogenesis, suppuration, granulation tissue, and fibrosis (healing; see Chapter 3 , Inflammation and Healing).
Additionally, roughened surfaces can also occur when an organ, such as the liver or kidney, is sectioned with a knife or scalpel blade and the “cut” surface is illuminated and photographed (see Fig. I.1, E). The cut surface exposes internal structures, such as glomeruli, renal tubules, microvessels, hepatic lobules, bile canaliculi, and/or nodular aggregates of leukocytes (neoplasia or inflammation), that may project irregularly outward and give the cut surface a roughened appearance (see Fig. I.1, D and F). This internal structure may be “normal” or may be caused by injury or inflammation of the tissue or organ; however, in either case, specular highlights may be present on gross images. Lastly, in many instances, specular highlights are a blend of the two basic types (solid vs. dots) previously discussed with the central area of the highlight being solid and the periphery consisting of pinpoints to small dots (see Fig. I.1, B, C, and F). This outcome occurs when the surface has intermixed smooth and roughened areas and/or there is convex curvature of the surface, such as occurs with intestines.
For more information on specular highlights and the physics of why they occur on the surfaces of specimens, see https://www. physicsclassroom.com/class/refln/Lesson-1/Specular-vs-DiffuseReflection
Colors of Normal Tissues and Organs
Throughout this book, students will find numerous photographs of gross lesions that occur in diseases of domestic animals (horses,
cattle, sheep, goats, pigs, dogs, and cats). They will learn how to recognize, evaluate, and interpret changes in tissue and organs and to recognize the characteristics of the lesions that assist in establishing morphologic diagnoses. Thus, recognizing the colors of normal tissues and organs is an essential first step in this process.f To begin, the basic colors of normal tissues and organs are a mixture of color densities (light to dark) arising from the hues and/or shades of the five colors listed:
• white to gray, attributable to proteins, minerals, and lipids that contribute to the structure of the cells;
• yellow, attributable to substances such as lipids, carotene pigments, cytochromes, lipochromes, bilirubin, amyloid, and hemosiderin;
• red, attributable to blood (i.e., erythrocytes) flowing through or trapped within the circulatory system and microcirculation of the tissue or organ;
• brown, attributable to melanin pigments, myoglobin, cytochromes, bilirubin, hemosiderin, and hematin; and
• black, attributable to melanin pigments and hematin or other exogenous pigments.
The natural colors of cells and thus of tissues and organs are determined by molecules that contribute to the structure of the cell and by substances that are synthesized by or accumulate within the cell. Secondly, the colors of tissues and organs are also influenced by the number of erythrocytes within them. Each of these tissues and organs has a unique structurally defined microcirculation that facilitates the exchange of nutrients and waste products between erythrocytes and extravascular tissue. Thus, the natural color of each tissue and organ is also blended with colors of the red spectrum that are contributed by erythrocytes, which flow through the microcirculation of these tissues and organs. These relationships are explained in greater detail as follows:
• Colors of Molecules/Substances Contained within Normal Cells: In homeostasis, the overall color of a tissue or organ is determined by the color of the cells that make up the tissue and organ. As a general rule, parenchymal and stromal cells (also leukocytes) appear white to light yellow because the molecules that make up the structure of these cells are predominately proteins and lipids. Nevertheless, cells can have a range of inherent colors if they, in homeostasis, have inborn, synthesized, or accumulated pigments, such as melanin (e.g., skin [light brown to brown-black]); myoglobin (e.g., skeletal and cardiac muscle [red to red-brown]); cytochromes (e.g., liver, kidney, and endocrine glands [dark red to brown]); bilirubin and iron (e.g., liver [dark red-brown]); lipochromes/lipofuscin (e.g., liver, heart, brain [yellow to light brown]); and carotenes/carotenoids (e.g., fat [yellow]).
• Colors of Erythrocytes and the Microcirculation: Erythrocytes and their interactions with the microcirculation also play a key role in determining the color of tissues and organs. Erythrocytes contain hemoglobin, an iron-protein complex (i.e., hemoprotein) that transports and exchanges oxygen and carbon dioxide throughout the body. Well-oxygenated hemoglobin gives erythrocytes their normal red color; poorly oxygenated hemoglobin gives erythrocytes a dark red to red-brown color or even the blue color of venous blood. Consequently, well-oxygenated erythrocytes give tissues and organs a faint pink to red color. The degree of pink to red coloring is also influenced by the quantity of erythrocytes retained in the tissue or organ as regulated by the microcirculation, which serves as the conduit to move erythrocytes
fFor photographs of the colors of normal organs see Appendix E-Table D.1, Colors of Normal Tissues and Organs.
I.1 Examples of Specular Highlights. A, Scrotal hernia, scrotum, pig. The arrows identify several areas of specular highlights of varied sizes on “normal” smooth shiny and wet surfaces (serosae [peritoneum]). t, Testis. B, Chronic passive congestion, liver, dog. The arrows identify several areas of specular highlights on smooth shiny surfaces (serosae [peritoneum]). These areas should not be confused with areas of capsular fibrosis (asterisks) or acute inflammation and/or fibrin accumulation (not shown here). Note that the areas of capsular fibrosis show variations in shape, size, texture, and color (whitish-gray). C, Kidney, capsular surface, granulomatous nephritis, dog. Specular highlights occur most commonly and intensely on smooth shiny surfaces (solid bright white areas [arrows]) such as the capsule of the kidney. Note the pinpoint or spotlike circular to elliptical white highlights haphazardly arranged singularly or in small groups around the central large areas of solid white highlights. Lastly, there are multiple subcapsular, cortical, whitish-gray-red, raised granulomas (arrowheads) caused by migrating ascarid larvae; they look distinctly different from the specular highlights. D, Emphysema, urinary bladder mucosa, cow. Multiple mucosal swellings (asterisks) have formed as a result of gas bubbles that have expanded the mucosa and are secondary to bacterial infection of the lower urinary tract. Inset: Note that the swellings contain numerous smaller bubbles (arrowhead) that have roughened (raised) the mucosal surfaces. Pinpoint specular highlights have formed on the surfaces of most of these bubbles (arrow). E, Proliferative glomerulonephritis, kidney, dorsal section, dog. Numerous bright white pinpoint to spotlike specular highlights of varied, but usually small, sizes (arrows) occur on roughened surfaces (boxes with black dashed lines) caused by enlarged glomeruli. Affected glomeruli are small, yellow-tan, ovoid raised foci (boxes with white dashed lines) that project outward from the cut surface of the cortex. A few of these glomeruli have pinpoint bright white specular highlights on their surfaces. F, Uremic pneumopathy from chronic renal failure, lung, 4-year-old dog. All of the lung lobes are gray-white-red because of extensive mineralization of alveolar walls and contiguous pleura. This lesion has “roughened” the pleural surface of the entire lung. Specular highlights (asterisk and box with black dashed lines) are most prominent on the convex surfaces of the caudal and middle lung lobes. The more uniform convex surface of the middle area of the caudal lobe favors the formation of uniform solid specular highlights (asterisk), whereas the more roughened texture of the pleural surface of the middle lung lobe (box with black dashed lines) favors the formation of pinpoint or spotlike circular to elliptical white specular highlights haphazardly arranged singularly or in small groups. Uniform solid specular highlights may have pinpoint or spotlike circular highlights at their periphery (asterisk) as the result of roughened or uneven surfaces. Lastly, it is important to notice the areas (boxes with white dashed lines) of extensive gray-white-red mineralization of alveolar walls and contiguous pleura and the absence of specular highlights in these areas even when the pleural surface is uneven/roughened. In the photographic process, these areas receive ambient light and are not directly exposed to light rays from the light source. For more information on specular highlights and the physics of why they occur on the surface of specimens, see https://www.physicsclassroom.com/class/refln/Lesson-1/Specular-vs-Diffuse-Reflec tion. (A courtesy Dr. H. Gelberg, College of Veterinary Medicine, Oregon State University. B courtesy College of Veterinary Medicine, North Carolina State University. C courtesy Dr. W. Crowell, College of Veterinary Medicine, The University of Georgia; and Noah’s Arkive, College of Veterinary Medicine, The University of Georgia. D and D insetcourtesy Dr. M.D. McGavin, College of Veterinary Medicine, University of Tennessee. E courtesy Dr. S.J. Newman, College of Veterinary Medicine, University of Tennessee. F courtesy Dr. A. López, Atlantic Veterinary College.)